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Sulforaphane treatment of autism spectrum disorder (ASD).

Singh K, Connors SL, Macklin EA, Smith KD, Fahey JW, Talalay P, Zimmerman AW.

Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15550-5. doi: 10.1073/pnas.1416940111. Epub 2014 Oct 13.

PMID: 25313065 Free PMC Article

Abstract

Autism spectrum disorder (ASD), characterized by both impaired communication and social interaction, and by stereotypic behavior, affects about 1 in 68, predominantly males. The medico-economic burdens of ASD are enormous, and no recognized treatment targets the core features of ASD. In a placebo-controlled, double-blind, randomized trial, young men (aged 13-27) with moderate to severe ASD received the phytochemical sulforaphane (n = 29)--derived from broccoli sprout extracts--or indistinguishable placebo (n = 15). The effects on behavior of daily oral doses of sulforaphane (50-150 µmol) for 18 wk, followed by 4 wk without treatment, were quantified by three widely accepted behavioral measures completed by parents/caregivers and physicians: the Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Clinical Global Impression Improvement Scale (CGI-I). Initial scores for ABC and SRS were closely matched for participants assigned to placebo and sulforaphane. After 18 wk, participants receiving placebo experienced minimal change (<3.3%), whereas those receiving sulforaphane showed substantial declines (improvement of behavior): 34% for ABC (P < 0.001, comparing treatments) and 17% for SRS scores (P = 0.017). On CGI-I, a significantly greater number of participants receiving sulforaphane had improvement in social interaction, abnormal behavior, and verbal communication (P = 0.015-0.007). Upon discontinuation of sulforaphane, total scores on all scales rose toward pretreatment levels. Dietary sulforaphane, of recognized low toxicity, was selected for its capacity to reverse abnormalities that have been associated with ASD, including oxidative stress and lower antioxidant capacity, depressed glutathione synthesis, reduced mitochondrial function and oxidative phosphorylation, increased lipid peroxidation, and neuroinflammmation.

 

Variation in Methylmercury Metabolism and Elimination Status (MerMES) in Humans Following Fish Consumption.

Caito SW, Jackson BP, Punshon T, Scrimale T, Grier A, Gill SR, Love TM, Watson GE, van Wijngaarden E, Rand MD.

Toxicol Sci. 2017 Nov 14. doi: 10.1093/toxsci/kfx226. [Epub ahead of print]

PMID: 29145616

Abstract

Evaluating the potential for methylmercury (MeHg) toxicity relies on accurately predicting the mercury (Hg) body burden that results from eating fish. Hg body burden is directly determined by the slow elimination kinetics of MeHg in the human body (kel ∼0.014days-1 or t1/2∼ 50days). Existing studies on MeHg half-life in humans demonstrate a wide range values (t1/2 = 30 to > 150days) and has lead to uncertainty in the derivation of a regulatory standard for acceptable daily oral intake. The causes of variation in MeHg toxicokinetics in humans remain little explored. Here we characterize variation in human MeHg metabolism and elimination rate (kel) in 37 adult volunteers who consumed three fish meals. We determined MeHg elimination rates via longitudinal Hg analysis in single hairs using laser ablation ICP-MS. We also measured MeHg metabolism (biotransformation) via speciation of fecal Hg. We find an average kel = 0.0157days-1 (t1/2 = 44days) amongst a more than two-fold variation in kel across the cohort (0.0248-0.0112days-1; t1/2 = 28-62days). While MeHg biotransformation varied widely between individuals, it showed a positive association with elimination rates across the cohort. A more than two-fold change in kel over a period of two years was seen in some individuals. In two individuals, who received antibiotic for unrelated health issues, elimination rate was seen to slow significantly. Associations of kel with age, BMI, gender and fish eating habits were not observed. We establish that a measure of methylmercury metabolism and elimination status (MerMES) can reduce uncertainty in determining an individual's MeHg toxicokinetics subsequent to eating fish.

KEYWORDS:

Methylmercury; biotransformation; elimination; half-life; laser ablation ICP-MS; metabolism; toxicokinetics

 

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Nut Consumption and Risk of Cardiovascular Disease.

Guasch-Ferré M, Liu X, Malik VS, Sun Q, Willett WC, Manson JE, Rexrode KM, Li Y, Hu FB, Bhupathiraju SN.

J Am Coll Cardiol. 2017 Nov 14;70(20):2519-2532. doi: 10.1016/j.jacc.2017.09.035.

PMID: 29145952

http://sci-hub.cc/10.1016/j.jacc.2017.09.035

Abstract

BACKGROUND:

The associations between specific types of nuts, specifically peanuts and walnuts, and cardiovascular disease remain unclear.

OBJECTIVES:

The authors sought to analyze the associations between the intake of total and specific types of nuts and cardiovascular disease, coronary heart disease, and stroke risk.

METHODS:

The authors included 76,364 women from the Nurses' Health Study (1980 to 2012), 92,946 women from the Nurses' Health Study II (1991 to 2013), and 41,526 men from the Health Professionals Follow-Up Study (1986 to 2012) who were free of cancer, heart disease, and stroke at baseline. Nut consumption was assessed using food frequency questionnaires at baseline and was updated every 4 years.

RESULTS:

During 5,063,439 person-years of follow-up, the authors documented 14,136 incident cardiovascular disease cases, including 8,390 coronary heart disease cases and 5,910 stroke cases. Total nut consumption was inversely associated with total cardiovascular disease and coronary heart disease after adjustment for cardiovascular risk factors. The pooled multivariable hazard ratios for cardiovascular disease and coronary heart disease among participants who consumed 1 serving of nuts (28 g) 5 or more times per week, compared with the reference category (never or almost never), were 0.86 (95% confidence interval: 0.79 to 0.93; p for trend = 0.0002) and 0.80 (95% confidence interval: 0.72 to 0.89; p for trend <0.001), respectively. Consumption of peanuts and tree nuts (2 or more times/week) and walnuts (1 or more times/week) was associated with a 13% to 19% lower risk of total cardiovascular disease and 15% to 23% lower risk of coronary heart disease.

CONCLUSIONS:

In 3 large prospective cohort studies, higher consumption of total and specific types of nuts was inversely associated with total cardiovascular disease and coronary heart disease.

KEYWORDS:

cardiovascular disease; coronary heart disease; nuts; peanuts; stroke; tree nuts

 

A comparative study of the effect of green tea and sour tea on blood pressure and lipid profile in healthy adult men.

Kafeshani M, Entezari MH, Karimian J, Pourmasoumi M, Maracy MR, Amini MR, Hadi A.

ARYA Atheroscler. 2017 May;13(3):109-116.

PMID: 29147120

Abstract

BACKGROUND:

Cardiovascular diseases (CVD) are a set of metabolic disorders affecting heart and blood vessels. Green tea and sour tea (Hibiscus sabdariffa L.) have attracted significant attention recently due to their high popularity, nutrient profile and therapeutic effects. The aim of the present study was to compare the effects of green tea and sour tea supplementation on blood pressure and lipid profile in healthy adult men.

METHODS:

This randomized, double-blind, placebo-controlled trial included 54 healthy adult men. The participants were randomly assigned to two intervention groups receiving 450 mg green tea or sour tea and one placebo group which consumed 450 mg placebo (maltodextrin) for 6 weeks. Blood pressure, lipid profile, dietary intake and physical activity were measured pre- and post-intervention and compared.

RESULTS:

After 6 weeks of intervention, sour tea supplementation led to a significant decrease in systolic blood pressure (SBP) compared with the placebo group. However, we faild to find any significant difference in SBP between green tea and control groups. Also, no significant changes were observed in diastolic blood pressure (DBP) and lipid profile between the three groups. In comparison with baseline, there was a significant increase in the mean level of serum high-density lipoprotein cholesterol (HDL-C) in green tea and sour tea groups. Also, the interventions resulted in significant decrease in the mean levels of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and DBP in the sour tea group compared with the pre-intervention value.

CONCLUSION:

On the basis of our findings, sour tea supplementation led to decreased SBP in healthy men compared with the placebo, but there was no significant difference between their effects on DBP and lipid profile.

KEYWORDS:

Adults; Blood Pressure; Green Tea; Hibiscus Sabdariffa

 

Adherence to Mediterranean diet and subjective cognitive function in men.

Bhushan A, Fondell E, Ascherio A, Yuan C, Grodstein F, Willett W.

Eur J Epidemiol. 2017 Nov 17. doi: 10.1007/s10654-017-0330-3. [Epub ahead of print]

PMID: 29147948

Abstract

Benefits of a Mediterranean diet for cognition have been suggested, but epidemiologic studies have been relatively small and of limited duration. To prospectively assess the association between long-term adherence to a Mediterranean dietary pattern and self-reported subjective cognitive function (SCF). Prospective observational study. The Health Professionals' Follow-up Study, a prospective cohort of 51,529 men, 40-75 years of age when enrolled in 1986, of whom 27,842 were included in the primary analysis. Mediterranean diet (MD) score, computed from the mean of five food frequency questionnaires, assessed every 4 years from 1986 to 2002. Self-reported SCF assessed by a 6-item questionnaire in 2008 and 2012, and validated by association with genetic variants in apolipoprotein-4. Using the average of 2008 and 2012 SCF scores, 38.0% of men were considered to have moderate memory scores and 7.3% were considered to have poor scores. In a multivariate model, compared with men having a MD score in the lowest quintile, those in the highest quintile had a 36% lower odds of a poor SCF score (odds ratio 0.64, 95% CI 0.55-0.75; P, trend < 0.001) and a 24% lower odds of a moderate SCF score (OR 0.76, 95% CI 0.70-0.83; P, trend < 0.001). Both remote and more recent diet contributed to this relation. Associations were only slightly weaker using baseline dietary data and a lag of 22 years. Long-term adherence to the Mediterranean diet pattern was strongly related to lower subjective cognitive function. These findings provide further evidence that a healthy dietary pattern may prevent or delay cognitive decline.

KEYWORDS:

Alzheimer’s disease; Mediterranean diet; Mild cognitive impairment; Subjective cognitive decline; Subjective cognitive function

 

Adherence to Hunger Training over 6 Months and the Effect on Weight and Eating Behaviour: Secondary Analysis of a Randomised Controlled Trial.

Jospe MR, Taylor RW, Athens J, Roy M, Brown RC.

Nutrients. 2017 Nov 17;9(11). pii: E1260. doi: 10.3390/nu9111260.

PMID: 29149038

Abstract

Monitoring blood glucose prior to eating can teach individuals to eat only when truly hungry, but how adherence to 'hunger training' influences weight loss and eating behaviour is uncertain. This exploratory, secondary analysis from a larger randomized controlled trial examined five indices of adherence to 'hunger training', chosen a priori, to examine which adherence measure best predicted weight loss over 6 months. We subsequently explored how the best measure of adherence influenced eating behavior in terms of intuitive and emotional eating. Retention was 72% (n = 36/50) at 6 months. Frequency of hunger training booklet entry most strongly predicted weight loss, followed by frequency of blood glucose measurements. Participants who completed at least 60 days of booklet entry (of recommended 63 days) lost 6.8 kg (95% CI: 2.6, 11.0; p < 0.001) more weight than those who completed fewer days. They also had significantly higher intuitive eating scores than those who completed 30 days or less of booklet entry; a difference (95% CI) of 0.73 (0.12, 1.35) in body-food choice congruence and 0.79 (0.06, 1.51) for eating for physical rather than emotional reasons. Adherent participants also reported significantly lower scores for emotional eating of -0.70 (-1.13, -0.27). Following hunger training and focusing on simply recording ratings of hunger on a regular basis can produce clinically significant weight loss and clinically relevant improvements in eating behaviour.

KEYWORDS:

adherence; blood glucose self-monitoring; food intake regulation; hunger; obesity

 

Sudden Cardiac Arrest during Participation in Competitive Sports.

Landry CH, Allan KS, Connelly KA, Cunningham K, Morrison LJ, Dorian P; Rescu Investigators.

N Engl J Med. 2017 Nov 16;377(20):1943-1953. doi: 10.1056/NEJMoa1615710.

PMID: 29141175

Abstract

BACKGROUND:

The incidence of sudden cardiac arrest during participation in sports activities remains unknown. Preparticipation screening programs aimed at preventing sudden cardiac arrest during sports activities are thought to be able to identify at-risk athletes; however, the efficacy of these programs remains controversial. We sought to identify all sudden cardiac arrests that occurred during participation in sports activities within a specific region of Canada and to determine their causes.

METHODS:

In this retrospective study, we used the Rescu Epistry cardiac arrest database (which contains records of every cardiac arrest attended by paramedics in the network region) to identify all out-of-hospital cardiac arrests that occurred from 2009 through 2014 in persons 12 to 45 years of age during participation in a sport. Cases were adjudicated as sudden cardiac arrest (i.e., having a cardiac cause) or as an event resulting from a noncardiac cause, on the basis of records from multiple sources, including ambulance call reports, autopsy reports, in-hospital data, and records of direct interviews with patients or family members.

RESULTS:

Over the course of 18.5 million person-years of observation, 74 sudden cardiac arrests occurred during participation in a sport; of these, 16 occurred during competitive sports and 58 occurred during noncompetitive sports. The incidence of sudden cardiac arrest during competitive sports was 0.76 cases per 100,000 athlete-years, with 43.8% of the athletes surviving until they were discharged from the hospital. Among the competitive athletes, two deaths were attributed to hypertrophic cardiomyopathy and none to arrhythmogenic right ventricular cardiomyopathy. Three cases of sudden cardiac arrest that occurred during participation in competitive sports were determined to have been potentially identifiable if the athletes had undergone preparticipation screening.

CONCLUSIONS:

In our study involving persons who had out-of-hospital cardiac arrest, the incidence of sudden cardiac arrest during participation in competitive sports was 0.76 cases per 100,000 athlete-years. The occurrence of sudden cardiac arrest due to structural heart disease was uncommon during participation in competitive sports.

 

Sympathetic neuron-associated macrophages contribute to obesity by importing and metabolizing norepinephrine.

Pirzgalska RM, Seixas E, Seidman JS, Link VM, Sánchez NM, Mahú I, Mendes R, Gres V, Kubasova N, Morris I, Arús BA, Larabee CM, Vasques M, Tortosa F, Sousa AL, Anandan S, Tranfield E, Hahn MK, Iannacone M, Spann NJ, Glass CK, Domingos AI.

Nat Med. 2017 Nov;23(11):1309-1318. doi: 10.1038/nm.4422. Epub 2017 Oct 9.

PMID: 29035364

Abstract

The cellular mechanism(s) linking macrophages to norepinephrine (NE)-mediated regulation of thermogenesis have been a topic of debate. Here we identify sympathetic neuron-associated macrophages (SAMs) as a population of cells that mediate clearance of NE via expression of solute carrier family 6 member 2 (SLC6A2), an NE transporter, and monoamine oxidase A (MAOA), a degradation enzyme. Optogenetic activation of the sympathetic nervous system (SNS) upregulates NE uptake by SAMs and shifts the SAM profile to a more proinflammatory state. NE uptake by SAMs is prevented by genetic deletion of Slc6a2 or inhibition of the encoded transporter. We also observed an increased proportion of SAMs in the SNS of two mouse models of obesity. Genetic ablation of Slc6a2 in SAMs increases brown adipose tissue (BAT) content, causes browning of white fat, increases thermogenesis, and leads to substantial and sustained weight loss in obese mice. We further show that this pathway is conserved, as human sympathetic ganglia also contain SAMs expressing the analogous molecular machinery for NE clearance, which thus constitutes a potential target for obesity treatment.

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Macrophages dispose of catecholamines in adipose tissue.

Czech MP.

Nat Med. 2017 Nov 7;23(11):1255-1257. doi: 10.1038/nm.4440. No abstract available.

PMID: 29117176

http://sci-hub.cc/10.1038/nm.4440

 

Mitochondrial Fission Promotes the Continued Clearance of Apoptotic Cells by Macrophages.

Wang Y, Subramanian M, Yurdagul A Jr, Barbosa-Lorenzi VC, Cai B, de Juan-Sanz J, Ryan TA, Nomura M, Maxfield FR, Tabas I.

Cell. 2017 Oct 5;171(2):331-345.e22. doi: 10.1016/j.cell.2017.08.041. Epub 2017 Sep 21.

PMID: 28942921

http://sci-hub.cc/10.1016/j.cell.2017.08.041

Abstract

Clearance of apoptotic cells (ACs) by phagocytes (efferocytosis) prevents post-apoptotic necrosis and dampens inflammation. Defective efferocytosis drives important diseases, including atherosclerosis. For efficient efferocytosis, phagocytes must be able to internalize multiple ACs. We show here that uptake of multiple ACs by macrophages requires dynamin-related protein 1 (Drp1)-mediated mitochondrial fission, which is triggered by AC uptake. When mitochondrial fission is disabled, AC-induced increase in cytosolic calcium is blunted owing to mitochondrial calcium sequestration, and calcium-dependent phagosome formation around secondarily encountered ACs is impaired. These defects can be corrected by silencing the mitochondrial calcium uniporter (MCU). Mice lacking myeloid Drp1 showed defective efferocytosis and its pathologic consequences in the thymus after dexamethasone treatment and in advanced atherosclerotic lesions in fat-fed Ldlr-/- mice. Thus, mitochondrial fission in response to AC uptake is a critical process that enables macrophages to clear multiple ACs and to avoid the pathologic consequences of defective efferocytosis in vivo.

KEYWORDS:

DRP1; apoptotic cells; atherosclerosis; calcium signaling; efferocytosis; macrophage; mitochondrial dynamics; mitochondrial fission; phagocytosis

 

Alcohol and cancer

The Lancet

Published: 18 November 2017

DOI: http://dx.doi.org/10.1016/S0140-6736(17)32868-4

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32868-4/fulltext

Summary

The Nov 7 publication of Alcohol and Cancer: a Statement of the American Society of Clinical Oncology (ASCO) emphasises the prominence of alcohol as a proven cause of many cancers. This view is not novel and comes exactly 30 years after a working group of the International Agency for Research on Cancer determined that alcoholic beverages were carcinogenic to humans. It has been echoed by other cancer societies since then but seemingly ignored by the wider medical community and by society. The influential endorsement by ASCO provides a powerful impetus to act on decades of evidence that alcohol harms health.

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[sci-Hub seems to be down for a few days, so I do not know whether the below papers can be pdf-availed via Sci-Hub when and if it comes back on.]

 

Resveratrol Enhances Exercise-Induced Cellular and Functional Adaptations of Skeletal Muscle in Older Men and Women.

Alway SE, McCrory JL, Kearcher K, Vickers A, Frear B, Gilleland DL, Bonner DE, Thomas JM, Donley DA, Lively MW, Mohamed JS.

J Gerontol A Biol Sci Med Sci. 2017 Nov 9;72(12):1595-1606. doi: 10.1093/gerona/glx089.

PMID: 28505227

https://academic.oup.com/biomedgerontology/article/72/12/1595/3824856

https://watermark.silverchair.com/glx089.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAcMwggG_BgkqhkiG9w0BBwagggGwMIIBrAIBADCCAaUGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM0O_bNptTH3d1Pmj7AgEQgIIBdqfQLOMIHCgvPDUmH3K7iJ3n7uVCm4jLaN0Tz38d8IqMN6B9KWgaMcQuvqqe-9YIJ_dvcmmUL3jVqBK8MkbDgHX_J9Llu6VE3vTQRT3EbQaVdjC2kKXaz_W56ooXOmjqJCWsHOJdfV5qt_m52m9-_xXuHfrs0IEbSa9Ik8YtgLX00TJVeKUFZMFc_VxP1drcmP00oJ-jzqs0_u7zMOAL5Rxmr9gJqo3q3qeoA-AvZPqa2vvYL9Ldib3mSfZUbeuyp-z0Hrmv2QngB2jhSbpKshENFPduH5X5pdFx-cesA_UAte8Pso1E-4EM3KEnd1p7FM5y-GMTsBG4Vl1ND2lgErtQ6kok98UQ0tjC1heYPXWQuBDfOuvVC7fL5LhdpCL4XngVy2r_giNb_JJFIxYXvxMIdCK37grdsBN_Er7vF4Q_zfHH50antjcQhGET2sGAjnki7OvEFuoWG3wt5JjU5mOQ7UFc5rPaJOFHCAGZZJra1Or5ajX0

Abstract

Older men (n = 12) and women (n = 18) 65-80 years of age completed 12 weeks of exercise and took either a placebo or resveratrol (RSV) (500 mg/d) to test the hypothesis that RSV treatment combined with exercise would increase mitochondrial density, muscle fatigue resistance, and cardiovascular function more than exercise alone. Contrary to our hypothesis, aerobic and resistance exercise coupled with RSV treatment did not reduce cardiovascular risk further than exercise alone. However, exercise added to RSV treatment improved the indices of mitochondrial density, and muscle fatigue resistance more than placebo and exercise treatments. In addition, subjects that were treated with RSV had an increase in knee extensor muscle peak torque (8%), average peak torque (14%), and power (14%) after training, whereas exercise did not increase these parameters in the placebo-treated older subjects. Furthermore, exercise combined with RSV significantly improved mean fiber area and total myonuclei by 45.3% and 20%, respectively, in muscle fibers from the vastus lateralis of older subjects. Together, these data indicate a novel anabolic role of RSV in exercise-induced adaptations of older persons and this suggests that RSV combined with exercise might provide a better approach for reversing sarcopenia than exercise alone.

KEYWORDS:

Exercise; Fatigue; Fiber type; Mitochondria; Muscle; Sarcopenia; Strength

 

[The below paper is pdf-availed.]

Dietary total, animal, vegetable calcium and type 2 diabetes incidence among Korean adults: The Korean Multi-Rural Communities Cohort (MRCohort).

Oh JM, Woo HW, Kim MK, Lee YH, Shin DH, Shin MH, Choi BY.

Nutr Metab Cardiovasc Dis. 2017 Oct 13. pii: S0939-4753(17)30232-6. doi: 10.1016/j.numecd.2017.10.005. [Epub ahead of print]

PMID: 29167059

Abstract

BACKGROUND AND AIMS:

Although a possible mechanism for developing type 2 diabetes in relation to calcium intake has been suggested, there is currently little epidemiological evidence on the association between dietary calcium and type 2 diabetes (T2D). This study aimed to evaluate the prospective association between dietary calcium and T2D incidence among adults 40 years of age or over, from the Multi-rural Communities Cohort (MRCohort), South Korea.

METHODS AND RESULTS:

In total, 8313 participants (3033 men and 5280 women) who did not have diabetes at baseline were recruited between 2005 and 2013. The incidence rate ratio (IRR) was estimated using a modified Poisson regression model with a robust error estimator. During follow-up (31,570 person-years), 322 T2D cases were newly diagnosed. Dietary calcium (total and vegetable calcium) were inversely associated with the risk of T2D incidence among women (IRR = 0.61, 95% CI = 0.43-0.86, P for trend = 0.007 in third tertile of baseline total calcium intake comparing to the first tertile; IRR = 0.57, 95% CI = 0.39-0.84, P for trend = 0.006 for baseline vegetable calcium intake), not for men. The tendency of those inverse associations remained in both the normal fasting blood glucose group and the impaired fasting blood glucose group and were independent of obesity, smoking, and magnesium intake.

CONCLUSIONS:

Total and vegetable calcium may be inversely associated with T2D incidence among women, regardless of impaired fasting blood glucose group or normal group. The associations may be potentially dose-responsive. Moderate dietary calcium may be related to lower risk of T2D incidence comparing to low intake group among women.

KEYWORDS:

Cohort; Dietary calcium; Prospective study; South Korean; Type 2 diabetes

 

Tree nut, peanut, and peanut butter intake and risk of postmenopausal breast cancer: The Netherlands Cohort Study.

van den Brandt PA, Nieuwenhuis L.

Cancer Causes Control. 2017 Nov 22. doi: 10.1007/s10552-017-0979-7. [Epub ahead of print]

PMID: 29168062

https://link.springer.com/article/10.1007%2Fs10552-017-0979-7

https://link.springer.com/content/pdf/10.1007%2Fs10552-017-0979-7.pdf

Abstract

PURPOSE:

Nut intake has been associated with reduced mortality and risk of cardiovascular diseases, but there is only limited evidence on cancer. We investigated the relationship between nut intake and risk of postmenopausal breast cancer, and estrogen/progesterone receptor (ER/PR) subtypes.

METHODS:

In The Netherlands Cohort Study, 62,573 women aged 55-69 years provided information on dietary and lifestyle habits in 1986. After 20.3 years of follow-up, 2,321 incident breast cancer cases and 1,665 subcohort members were eligible for multivariate case-cohort analyses.

RESULTS:

Total nut intake was significantly inversely related to ER negative (ER -) breast cancer risk, with HR 0.55 (95% CI 0.33-0.93) for those consuming at least 10 g nuts/day versus non-consumers (p trend = 0.025). There were no significant inverse associations with ER + or total breast cancer. While there was no variation between PR subtypes, the ER-PR- subtype was also significantly inversely associated with nut intake, with HR 0.53 (95% CI 0.29-0.99), p trend = 0.037. Intake of peanuts and tree nuts separately was also inversely related to ER - breast cancer subtypes, while no associations were found with peanut butter intake.

CONCLUSIONS:

Our findings suggest an inverse association between nut intake and ER - breast cancer, and no association with total or hormone receptor-positive subtypes.

KEYWORDS:

Breast cancer; Cohort study; Nuts; Peanut butter; Peanuts

 

[The first below paper is pdf-availed.]

Tyrosine improves working memory in a multitasking environment.

Thomas JR, Lockwood PA, Singh A, Deuster PA.

Pharmacol Biochem Behav. 1999 Nov;64(3):495-500.

PMID: 10548261

Abstract

Previous studies indicate that tyrosine may prove useful in promoting improved performance in situations in which performance is compromised by stress. To extend the generality of previous tyrosine findings, the present study examined the effects of tyrosine ingestion on performance during both a Multiple Task and a Simple Task battery. The multiple task battery was designed to measure working memory, arithmetic skills, and visual and auditory monitoring simultaneously, whereas the simple task battery measured only working memory and visual monitoring. Ten men and 10 women subjects underwent these batteries 1 h after ingesting 150 mg/kg of l-tyrosine or placebo. Administration of tyrosine significantly enhanced accuracy and decreased frequency of list retrieval on the working memory task during the multiple task battery compared with placebo. However, tyrosine induced no significant changes in performance on the arithmetic, visual, or auditory tasks during the Multiple Task, or modified any performance measures during the Simple Task battery. Blood levels of ACTH and cortisol were not, but heart rate and blood pressure were significantly increased during the performance tasks. The present results indicate that tyrosine may sustain working memory when competing requirements to perform other tasks simultaneously degrade performance, and that supplemental tyrosine may be appropriate for maintaining performance when mild to severe decrements are anticipated.

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Dose-Dependent Effects of Oral Tyrosine Administration on Plasma Tyrosine Levels and Cognition in Aging.

van de Rest O, Bloemendaal M, de Heus R, Aarts E.

Nutrients. 2017 Nov 23;9(12). pii: E1279. doi: 10.3390/nu9121279.

PMID: 29168741

http://www.mdpi.com/2072-6643/9/12/1279/htm

Abstract

The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults (aged 60-75 years) received a single administration of 100, 150, or 200 mg/kg body weight of tyrosine. For comparison, 17 young adults (aged 18-35 years) received a dose of 150 mg/kg body weight of tyrosine. Tyrosine plasma concentrations were determined before and 90, 120, 150, 180, 210, and 240 min after tyrosine intake. Working memory was assessed using the N-back task at 90 min after tyrosine administration. Older adults showed a dose-dependent increase in plasma tyrosine concentrations (p < 0.001), and the plasma response was higher than for young adults with the same dose (p < 0.001). Load-dependent working memory performance decreased with higher doses of tyrosine (p = 0.048), especially in older adults with greater dose-dependent plasma tyrosine responses (p = 0.035). Our results show an age-related increase in plasma tyrosine response, which was associated with a dose-dependent decline in cognitive functioning in older adults.

KEYWORDS:

aging; catecholamines; dopamine; dose-response; plasma amino acids; tyrosine; working memory

 

The Scientist » News & Opinion » Daily News

Olfaction Determines Weight in Mice

Animals lacking a sense of smell stayed thinner than their smelling counterparts, despite eating the same amount.

By Diana Kwon | July 5, 2017

https://www.the-scientist.com/?articles.view/articleNo/49798/title/Olfaction-Determines-Weight-in-Mice/&utm_campaign=NEWSLETTER_TS_The-Scientist-Daily_2016&utm_source=hs_email&utm_medium=email&utm_content=58741157&_hsenc=p2ANqtz-_LSXOlCr1QKQ-uRej0g61eQMeTxn59l1b9pOYzfOkDJ0dMHweqLWH1iS7GThpxT7NOv5biRpb2bbnuL97kgoGcUUJtdw&_hsmi=58741157

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[The below paper is pdf-availed.]

The Sense of Smell Impacts Metabolic Health and Obesity.

Riera CE, Tsaousidou E, Halloran J, Follett P, Hahn O, Pereira MMA, Ruud LE, Alber J, Tharp K, Anderson CM, Brönneke H, Hampel B, Filho CDM, Stahl A, Brüning JC, Dillin A.

Cell Metab. 2017 Jul 5;26(1):198-211.e5. doi: 10.1016/j.cmet.2017.06.015.

PMID: 28683287

KEYWORDS:

diet-induced obesity; energy balance; hyperosmia; hyposmia; insulin resistance; insulin-like growth factor 1 receptor; lipolysis; olfactory sensory neuron; thermogenesis

 

[The below paper is not pdf-availed.]

Frequency of Leaving the House and Mortality from Age 70 to 95.

Jacobs JM, Hammerman-Rozenberg A, Stessman J.

J Am Geriatr Soc. 2017 Nov 22. doi: 10.1111/jgs.15148. [Epub ahead of print]

PMID: 29164595

Abstract

OBJECTIVES:

To determine the association between frequency of leaving the house and mortality.

DESIGN:

Prospective follow-up of an age-homogenous, representative, community-dwelling birth cohort (born 1920-21) from the Jerusalem Longitudinal Study (1990-2015).

SETTING:

Home.

PARTICIPANTS:

Individuals aged 70 (n = 593), 78 (n = 973), 85 (n = 1164), and 90 (n = 645), examined in 1990, 1998, 2005, and 2010, respectively.

MEASUREMENTS:

Frequency of leaving the house, defined as daily (6-7/week), often (2-5/week), and rarely (≤1/week); geriatric assessment; all-cause mortality (2010-15). Kaplan-Meier survival charts and proportional hazards models adjusted for social (sex, marital status, financial status, loneliness), functional (sex, self-rated health, fatigue, depression, physical activity, activity of daily living difficulty), and medical (sex, chronic pain, visual impairment, hearing impairment, diabetes mellitus, hypertension, ischemic heart disease, chronic kidney disease) covariates.

RESULTS:

At ages 70, 78, 85, and 90, frequency of going out daily was 87.0%, 80.6%, 65.6%, and 48.4%; often was 6.4%, 9.5%, 17.4%, and 11.3%; and rarely was 6.6%, 10.0%, 17.0%, and 40.3% respectively. Decreasing frequency of going out was associated with negative social, functional, and medical characteristics. Survival rates were lowest among those leaving rarely and highest among those going out daily throughout follow-up. Similarly, compared with rarely leaving the house, unadjusted mortality hazard ratios (HRs) were lowest among subjects leaving daily and remained significant after adjustment for social, functional and medical covariates. Among subjects leaving often, unadjusted HRs showed a similar effect of smaller magnitude, with attenuation of significance after adjustment in certain models. Findings were unchanged after excluding subjects dying within 6 months of follow-up.

CONCLUSION:

In community-dwelling elderly adults aged 70 to 90, leaving the house daily was associated with lower mortality risk, independent of social, functional, or medical status.

KEYWORDS:

leaving the house; mortality; oldest old; survival

 

The impact of a low glycaemic index (GI) diet on simultaneous measurements of blood glucose and fat oxidation: A whole body calorimetric study.

Kaur B, Quek Yu Chin R, Camps S, Henry CJ.

J Clin Transl Endocrinol. 2016 Apr 26;4:45-52. doi: 10.1016/j.jcte.2016.04.003. eCollection 2016 Jun.

PMID: 29159130

http://www.sciencedirect.com/science/article/pii/S2214623716300060

https://ac.els-cdn.com/S2214623716300060/1-s2.0-S2214623716300060-main.pdf?_tid=7cebecae-d20e-11e7-84f8-00000aacb35f&acdnat=1511634712_d3389037551716611024606a67860a33

Abstract

OBJECTIVE:

Low glycaemic index (GI) foods are known to minimize large fluctuations in blood glucose levels and have been suggested to increase fat oxidation. The objective of this study was to simultaneously investigate glucose excursion and substrate oxidation in a whole body calorimetre when Chinese male subjects were provided a low or high GI meal.

MATERIALS/METHODS:

In a randomized, controlled crossover non blind design, 12 healthy Chinese male adults (BMI 21.8 ± 1.3 kgm-2) attended two sessions consisting of either four low or high glycaemic meals (LGI vs HGI). Breakfast, lunch and snack were consumed in a whole body calorimetre while dinner was consumed at home. Daily changes in glycaemic response (GR) and postprandial GR responses were measured using a continuous glucose monitoring system. The GR was further calculated to obtain the incremental area under the curve (iAUC) for glucose concentrations. Glycaemic variability was calculated as mean amplitude of glycaemic excursion (MAGE). Substrate oxidation was calculated by measuring respiratory quotient and urine nitrogen excretion.

RESULTS:

After LGI meals in the whole body calorimetre, iAUC for glucose (P = 0.008) was lower compared to the HGI session. The HGI treatment produced a significantly greater MAGE than the LGI treatment over the 24 hour period (P < 0.001). Additionally, higher fat oxidation and lower carbohydrate oxidation were observed following breakfast and lunch when comparing LGI to HGI (P < 0.05).

CONCLUSIONS:

Consumption of LGI meals was capable of attenuating 24-hour blood glucose profiles and decreasing postprandial glucose excursions in healthy Asian males. Additionally, LGI mixed meals were able to promote fat oxidation over carbohydrate oxidation when compared to HGI mixed meals. The consumption of low GI meals may be a strategic approach in improving overall glycaemia and increasing fat oxidation in Asians consuming a high carbohydrate diet.

KEYWORDS:

Asian; Continuous glucose monitoring; Diet; Energy flux; Fat oxidation; Glycaemic index

 

Maternal dietary manganese protects chick embryos against maternal heat stress via epigenetic-activated antioxidant and anti-apoptotic abilities.

Zhu Y, Lu L, Liao X, Li W, Zhang L, Ji C, Lin X, Liu HC, Odle J, Luo X.

Oncotarget. 2017 Sep 11;8(52):89665-89680. doi: 10.18632/oncotarget.20804. eCollection 2017 Oct 27.

PMID: 29163779

=20804&path[]=66268

Abstract

Maternal heat stress induced the aberrant epigenetic patterns resulting in the abnormal development of offspring embryos. It is unclear whether maternal dietary manganese supplementation as an epigenetic modifier could protect the chick embryonic development against maternal heat stress via epigenetic mechanisms. To test this hypothesis using an avian model, a completely randomized design with a 2 (maternal normal and high environmental temperatures of 21 and 32°C, respectively) × 3 (maternal dietary manganese sources, the control diet without manganese supplementation and the control diet + 120 mg/kg as either inorganic or organic manganese) factorial arrangement was adopted. Maternal environmental hyperthermia increased mRNA expressions of heat shock proteins 90 and 70, cyclin-dependent kinase 6 and B-cell CLL/lymphoma 2-associated X protein displaying oxidative damage and apoptosis in the embryonic heart. Maternal environmental hyperthermia impaired the embryonic development associated with the alteration of epigenetic status, as evidenced by global DNA hypomethylation and histone 3 lysine 9 hypoacetylation in the embryonic heart. Maternal dietary manganese supplementation increased the heart anti-apoptotic gene B-cell CLL/lymphoma 2 expressions under maternal environmental hyperthermia and manganese superoxide dismutase enzyme activity in the embryonic heart. Maternal dietary organic Mn supplementation effectively eliminated the impairment of maternal environmental hyperthermia on the embryonic development. Maternal dietary manganese supplementation up-regulated manganese superoxide dismutase mRNA expression by reducing DNA methylation and increasing histone 3 lysine 9 acetylation of its promoter. It is suggested that maternal dietary manganese addition could protect the chick embryonic development against maternal heat stress via enhancing epigenetic-activated antioxidant and anti-apoptotic abilities.

KEYWORDS:

apoptosis; chick embryo; epigenetics; manganese superoxide dismutase; maternal environmental hyperthermia

 

Chronic Psychological Stress Was Not Ameliorated by Omega-3 Eicosapentaenoic Acid (EPA).

Bradbury J, Myers SP, Meyer B, Brooks L, Peake J, Sinclair AJ, Stough C.

Front Pharmacol. 2017 Oct 31;8:551. doi: 10.3389/fphar.2017.00551. eCollection 2017.

PMID: 29163147

https://www.frontiersin.org/articles/10.3389/fphar.2017.00551/full

https://researchbank.swinburne.edu.au/file/0f53d3ef-dffc-43e8-965c-dd736f6bd23c/1/2017-bradbury-chronic_psychological_stress.pdf

Abstract

Background: Chronic psychological stress and mental health disorders are endemic in Western culture where population dietary insufficiencies of omega-3 fatty acids (n-3FA) from seafood have been observed. Objective: This study was designed to test for a causal relationship between one of the most active components of fish oil, eicosapentaenoic acid (EPA), and chronic psychological stress. Method: A randomized double-blind, placebo-controlled clinical trial with parallel-assignment to two groups was designed (Trial Id: ACTRN12610000404022). The interventions were four EPA-rich fish oil capsules per day, delivering 2.2 g/d EPA (and 0.44 g/d DHA), or identical placebo (low-phenolic olive oil capsules with 5% fish oil to aid blinding). The primary outcome was the between-group difference on the Perceived Stress Scale (PSS-10) after 12 weeks supplementation. An a priori power analysis determined that group sizes of 43 would provide 80% power to detect a significant between-group difference of 12.5%, at α = 0.05. Ninety community members (64 females, 26 males) reporting chronic work stress were recruited via public advertising in northern NSW, Australia. Results: At baseline the omega-3 index (EPA + DHA as % to total fatty acids in red blood cell membranes) was 5.2% in both groups (SD = 1.6% control group; 1.8% active group). After supplementation this remained stable at 5.3% (SD = 1.6%) for the control group but increased to 8.9% (SD = 1.5%) for the active group, demonstrating successful incorporation of EPA into cells. Intention-to-treat (ITT) analysis found no significant between-group differences in PSS outcome scores post-intervention (b = 1.21, p = 0.30) after adjusting for sex (b = 2.36, p = 0.079), baseline PSS (b = 0.42, p = 0.001) and baseline logEPA . Discussion: Treatment increased cell membrane EPA but, contrary to the hypothesis, there was no effect on perceived stress. Limitations included an imbalance of gender in groups after randomization (68% of the males were in the placebo group). While we found no significant interaction between sex and group on the outcome after adjusting for baseline PSS, larger studies with groups stratified for gender may be required to further confirm these findings. Conclusion: This study demonstrated that 2.2 g/day of EPA for 12 weeks did not reduce chronic psychological stress.

KEYWORDS:

chronic stress; coping; docosahexaenoic acid (DHA); eicosapentaenoic acid (EPA); fish oil; omega-3 fatty acids; proinflammatory cytokines; psychological stress

 

Effect of Chronic Administration of Resveratrol on Cognitive Performance during Aging Process in Rats.

Navarro-Cruz AR, Ramírez Y Ayala R, Ochoa-Velasco C, Brambila E, Avila-Sosa R, Pérez-Fernández S, Morales-Medina JC, Aguilar-Alonso P.

Oxid Med Cell Longev. 2017;2017:8510761. doi: 10.1155/2017/8510761. Epub 2017 Oct 15.

PMID: 29163756

https://www.hindawi.com/journals/omcl/2017/8510761/

Abstract

The increase in the elderly population has generated concern to meet health demands. The research efforts to elucidate the mechanisms of damage associated with aging have also been significantly increased, especially in order to avoid the reduction of the cognitive abilities in geriatric patients, resulting from the damage generated mainly at the level of the hippocampus during old age. At present, many studies describe resveratrol as an antiaging component. There are reports that it can activate the Sirt1 gene related to antiaging, emulating the effects obtained by caloric restriction in rodents. The aim of the study was to evaluate the effect of chronic administration of resveratrol (10 mg/kg) on cognitive performance in behavioral tests after 8 months of treatment and on the preservation of cerebral integrity in the cytoarchitecture of regions CA1 and CA2. Results showed that the cytoarchitecture of the CA1 and CA2 regions in the hippocampus retained their integrity over time in rats treated with resveratrol, and the behavioral test performed revealed that chronic resveratrol administration for 8 months showed improvements in cognitive performance. The results indicate that resveratrol may exhibit therapeutic potential for age-related conditions.

 

[The below paper is pdf-availed. It seemed that coffee was more effective for healthier folks.]

Association Between Coffee Intake After Diagnosis of Colorectal Cancer and Reduced mortality.

Hu Y, Ding M, Yuan C, Wu K, Smith-Warner SA, Hu FB, Chan AT, Meyerhardt JA, Ogino S, Fuchs CS, Giovannucci EL, Song M.

Gastroenterology. 2017 Nov 17. pii: S0016-5085(17)36368-0. doi: 10.1053/j.gastro.2017.11.010. [Epub ahead of print]

PMID: 29158191

Abstract

BACKGROUND & AIMS:

Few studies have examined the association between coffee intake and survival after diagnosis of colorectal cancer (CRC). We performed a prospective study to investigate the association between coffee intake after a diagnosis of CRC and mortality.

METHODS:

We collected data from the Nurses' Health Study (1984-2012) and Health Professionals Follow-up Study (1986-2012), following 1599 patients diagnosed with stage 1 or 2 CRC. CRC was reported on questionnaires and ascertained by review of medical records and pathology reports; intake of food and beverages was determined from responses to semi-quantitative food frequency questionnaires. Participants were asked how often during the previous year that they consumed coffee, with 1 cup as the standard portion size. The first questionnaire response collected at least 6 months but not more than 4 years after diagnosis was used for assessment of post-diagnostic intake (median time from diagnosis to the dietary assessment, 2.2 years). The last sFFQ prior to diagnosis was used to assess pre-diagnostic dietary intake.

RESULTS:

During a median of 7.8 years of follow-up, we documented 803 deaths, of which 188 were due to CRC. In the multivariable adjusted models, compared with nondrinkers, patients who consumed at least 4 cups of coffee per day had a 52% lower risk of CRC-specific death (hazard ratio {HR} 0.48; 95% CI, 0.28-0.83; P for trend=.003) and 30% reduced risk of all-cause death (HR, 0.70; 95% CI, 0.54-0.91; P for trend <.001). High intake of caffeinated and decaffeinated coffee (2 or more cups/day) was associated with lower risk of CRC-specific mortality and all-cause mortality. When coffee intake before vs after CRC diagnosis were examined, compared with patients consistently consuming low amounts (less than 2 cups/day), those who maintained a high intake (2 or more cups/day) had a significantly lower risk of CRC-specific death (multivariable HR, 0.63; 95% CI, 0.44-0.89) and death from any cause (multivariable HR, 0.71; 95% CI, 0.60-0.85).

CONCLUSIONS:

In an analysis data from the Nurses' Health Study and Health Professionals Follow-up Study, we associated intake of caffeinated and decaffeinated coffee after diagnosis of CRC with lower risk of CRC-specific death and overall death. Studies are needed to determine the mechanisms by which coffee might reduce CRC progression.

KEYWORDS:

colon cancer; diet; post-diagnostic coffee intake; rectal cancer

 

[The below paper is pdf-availed.]

The impact of folate intake on the risk of head and neck cancer in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) cohort.

Kawakita D, Lee YA, Gren LH, Buys SS, La Vecchia C, Hashibe M.

Br J Cancer. 2017 Nov 21. doi: 10.1038/bjc.2017.383. [Epub ahead of print]

PMID: 29161239

Abstract

BACKGROUND:

Although low levels of folate leads to disturbances in DNA replication, DNA methylation and DNA repair, the association between dietary folate intake and head and neck cancer (HNC) risk remains unclear.

METHODS:

We evaluated the association between folate intake and HNC risk using prospective cohort data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. This study included 101 700 participants and 186 cases with confirmed incident HNC. The median follow-up was 12.5 years. We estimated hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) using Cox proportional hazard model including age, sex, body mass index, education, race, tobacco smoking, alcohol drinking and total fruit and vegetable intake.

RESULTS:

Higher intake of food folate and fortified folic acid in foods was associated with a decreasing HNC risk in a dose-response manner. The HRs of highest vs the lowest quartile of intake were 0.35 (95%CI: 0.18-0.67) for food folate, and 0.49 (95%CI: 0.30-0.82) for fortified folic acid. Intakes of total folate, natural folate and supplemental folic acid were not associated with the risk of HNC and its subsites. We did not detect any interaction between smoking, drinking and food folate intake on HNC risk.

CONCLUSIONS:

These findings provide evidence of the protective role of dietary folate intake on HNC risk.

 

[The below paper is not pdf-availed.]

Ovarian Cancer Early Detection by Circulating CA125 in the context of Anti-CA125 Autoantibody Levels: Results from the EPIC cohort.

Fortner RT, Schock H, Le Cornet C, Hüsing A, Vitonis AF, Johnson TS, Fichorova RN, Fashemi T, Yamamoto HS, Tjønneland A, Hansen L, Overvad K, Boutron-Ruault MC, Kvaskoff M, Severi G, Boeing H, Trichopoulou A, Papatesta EM, La Vecchia C, Palli D, Sieri S, Tumino R, Sacerdote C, Mattiello A, Onland-Moret NC, Peeters PH, Bueno-de-Mesquita HBA, Weiderpass E, Quirós JR, Duell EJ, Sánchez MJ, Navarro C, Ardanaz E, Larrañaga N, Nodin B, Jirström K, Idahl A, Lundin E, Khaw KT, Travis RC, Gunter M, Johansson M, Dossus L, Merritt MA, Riboli E, Terry KL, Cramer DW, Kaaks R.

Int J Cancer. 2017 Nov 21. doi: 10.1002/ijc.31164. [Epub ahead of print]

PMID: 29159934

Abstract

CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non-cases. Anti-CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non-cases. We investigated these objectives using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to 4 matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2-year lag-time intervals were calculated using conditional logistic regression calibrated towards the absolute risk estimates from a pre-existing epidemiological risk model as an offset-variable. Anti-CA125 levels alone did not discriminate cases from controls. For cases diagnosed <2 years after blood collection, discrimination by CA125 antigen was suggestively higher with higher anti-CA125 levels (aAUC, highest antibody tertile: 0.84 [0.76-0.92]; lowest tertile: 0.76 [0.67-0.86]; phet =0.06). We provide the first evidence of potentially synergistic discrimination effects of CA125 and anti-CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection.

KEYWORDS:

CA125; MUC16; anti-CA125 antibodies; autoantibodies; early detection markers; ovarian cancer

 

Gallstone Disease and the Risk of Type 2 Diabetes.

Lv J, Yu C, Guo Y, Bian Z, Yang L, Chen Y, Li S, Huang Y, Fu Y, He P, Tang A, Chen J, Chen Z, Qi L, Li L.

Sci Rep. 2017 Nov 20;7(1):15853. doi: 10.1038/s41598-017-14801-2.

PMID: 29158491

https://www.nature.com/articles/s41598-017-14801-2

https://www.nature.com/articles/s41598-017-14801-2.pdf

Abstract

Gallstone disease (GSD) is related to several diabetes risk factors. The present study was to examine whether GSD was independently associated with type 2 diabetes in the China Kadoorie Biobank study. After excluding participants with prevalent diabetes and prior histories of cancer, heart disease, and stroke at baseline, 189,154 men and 272,059 women aged 30-79 years were eligible for analysis. The baseline prevalence of GSD was 5.7% of the included participants. During 4,138,687 person-years of follow-up (median, 9.1 years), a total of 4,735 men and 7,747 women were documented with incident type 2 diabetes. Compared with participants without GSD at baseline, the multivariate-adjusted hazard ratios (HRs) for type 2 diabetes for those with GSD were 1.09 (95% CI: 0.96-1.24; P = 0.206), 1.21 (95% CI: 1.13-1.30; P < 0.001), and 1.17 (95% CI: 1.10-1.25; P < 0.001) in men, women, and the whole cohort respectively. There was no statistically significant heterogeneity between men and women (P = 0.347 for interaction). The association between GSD and type 2 diabetes was strongest among participants who reported ≥5 years since the first diagnosis and were still on treatment at baseline (HR = 1.48; 95% CI: 1.16-1.88; P = 0.001). The present study highlights the importance of developing a novel prevention strategy to mitigate type 2 diabetes through improvement of gastrointestinal health.

 

[The below paper is pdf-availed.]

https://en.wikipedia.org/wiki/Hyoscine#Adverse_effects

Contribution of M<sub>1</sub> and M<sub>2</sub> muscarinic receptor subtypes to convulsions in fasted mice treated with scopolamine and given food.

Bacanak MS, Aydın B, Cabadak H, Nurten A, Gören MZ, Enginar N.

Behav Brain Res. 2017 Nov 17. pii: S0166-4328(17)31301-3. doi: 10.1016/j.bbr.2017.11.018. [Epub ahead of print]

PMID: 29158113

Abstract

Treatment of fasted mice and rats with the nonselective muscarinic antagonist, scopolamine or atropine, causes convulsions after food intake. This study evaluated the effect of fasting on the expression of M1 and M2 muscarinic receptors in the brain regions, the relationship between receptor expression and seizure stages, and the muscarinic receptor subtype which plays a role in the occurrence of convulsions. Mice were grouped as allowed to eat ad lib (fed) and deprived of food for 24hours (fasted). Fasted animals developed convulsions after being treated with scopolamine (60%) or the selective M1 receptor antagonist pirenzepine (10mg/kg; 20% and 60mg/kg; 70%) and given food. Fasting increased expression of M1 receptors in the frontal cortex and M2 receptors in the hippocampus, but produced no change in the expression of both receptors in the amygdaloid complex. Food intake after fasting decreased M1 receptor expression in the frontal cortex and M1 and M2 receptor expression in the hippocampus. Seizure severity was uncorrelated with muscarinic receptor expression in the brain regions. Taken together, these findings provide evidence for the role of M1 muscarinic receptor antagonism and fasting-induced increases in M1 and M2 expression possible underlying mechanism in the occurrence of convulsions in fasted animals.

KEYWORDS:

M(1); M(2) muscarinic receptor expression; convulsion; fasting; food intake; pirenzepine; scopolamine

Edited by AlPater

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Apolipoprotein E gene polymorphism modifies fasting total cholesterol concentrations in response to replacement of dietary saturated with monounsaturated fatty acids in adults at moderate cardiovascular disease risk.

Shatwan IM, Weech M, Jackson KG, Lovegrove JA, Vimaleswaran KS.

Lipids Health Dis. 2017 Nov 23;16(1):222. doi: 10.1186/s12944-017-0606-3.

PMID: 29169396

https://lipidworld.biomedcentral.com/articles/10.1186/s12944-017-0606-3

https://lipidworld.biomedcentral.com/track/pdf/10.1186/s12944-017-0606-3?site=lipidworld.biomedcentral.com

Abstract

BACKGROUND:

Consumption of ≤10% total energy from fat as saturated fatty acids (SFA) is recommended for cardiovascular disease risk reduction in the UK; however there is no clear guidance on the optimum replacement nutrient. Lipid-associated single-nucleotide polymorphisms (SNPs) have been shown to modify the lipid responses to dietary fat interventions. Hence, we performed a retrospective analysis in 120 participants from the Dietary Intervention and VAScular function (DIVAS) study to investigate whether lipoprotein lipase (LPL) and apolipoprotein E (APOE) SNPs modify the fasting lipid response to replacement of SFA with monounsaturated (MUFA) or n-6 polyunsaturated (PUFA) fatty acids.

METHODS:

The DIVAS study was a randomized, single-blinded, parallel dietary intervention study performed in adults with a moderate cardiovascular risk who received one of three isoenergetic diets rich in SFA, MUFA or n-6 PUFA for 16 weeks.

RESULTS:

After the 16-week intervention, a significant diet-gene interaction was observed for changes in fasting total cholesterol (P = 0.001). For the APOE SNP rs1064725, only TT homozygotes showed a significant reduction in total cholesterol after the MUFA diet (n = 33; -0.71 ± 1.88 mmol/l) compared to the SFA (n = 38; 0.34 ± 0.55 mmol/l) or n-6 PUFA diets (n = 37; -0.08 ± 0.73 mmol/l) (P = 0.004). None of the interactions were statistically significant for the other SNPs.

CONCLUSIONS:

In summary, our findings have demonstrated a greater sensitivity of the APOE SNP rs1064725 to dietary fat composition, with a total cholesterol lowering effect observed following substitution of SFA with MUFA but not n-6 PUFA. Further large intervention studies incorporating prospective genotyping are required to confirm or refute our findings.

KEYWORDS:

Apolipoprotein E polymorphism; DIVAS; Gene-diet interaction; Monounsaturated fatty acids; Saturated fatty acids; Total cholesterol

 

Socio-economic indicators and diet quality in an older population.

Schoufour JD, de Jonge EAL, Kiefte-de Jong JC, van Lenthe FJ, Hofman A, Nunn SPT, Franco OH.

Maturitas. 2018 Jan;107:71-77. doi: 10.1016/j.maturitas.2017.10.010. Epub 2017 Oct 16.

PMID: 29169585

http://www.sciencedirect.com/science/article/pii/S037851221730796X

https://ac.els-cdn.com/S037851221730796X/1-s2.0-S037851221730796X-main.pdf?_tid=03a2518a-d2db-11e7-8fc6-00000aab0f6b&acdnat=1511722556_9f78c4005631ad84cf352a2fc30fbe3d

Abstract

PURPOSE:

To examine the strength and independence of associations between three major socio-economic indicators (income, education and occupation) and diet quality (DQ) at baseline and after 20-year follow-up.

METHODS:

Cross-sectional and longitudinal analyses using data collected in the Rotterdam Study, a prospective population-based cohort. Participants were categorised according to socio-economic indicators (education, occupation and household income) measured at baseline (1989-1993). Participants aged 55 years or older were included (n=5434). DQ was assessed at baseline (1989-1993) and after 20 years (2009-2011) and quantified using the Dutch Healthy Diet Index, reflecting adherence to the Dutch guidelines for a healthy diet; scores can range from 0 (no adherence) to 80 (optimal adherence). Linear regression models were adjusted for sex, age, smoking status, BMI, physical activity level, total energy intake and mutually adjusted for the other socio-economic indicators.

RESULTS:

At baseline, scores on the Dutch Healthy Diet Index were 2.29 points higher for participants with the highest level of education than for those with the lowest level (95%CI=1.23-3.36); in addition, they were more likely to have a higher DQ at follow-up (β=3.10, 95%CI=0.71-5.50), after adjustment for baseline DQ. In contrast, higher income was associated with lower DQ at follow-up (β=-1.92, 95%CI=-3.67, -0.17), whereas occupational status was not associated with DQ at baseline or at follow-up.

CONCLUSION:

In our cohort of Dutch participants, a high level of education was the most pronounced socio-economic indicator of high DQ at baseline and at follow-up. Our results highlight that different socio-economic indicators influence DQ in different ways.

KEYWORDS:

Diet quality; Education; Older age; Socio-economic indicators

 

[The below paper's pdf is availed from:

]https://www.soa.org/Library/Monographs/Life/Living-To-100/2017/table-of-contents.aspx]

Historical Evolution of Old-Age Mortality and New Approaches to Mortality Forecasting.

Gavrilov LA, Gavrilova NS, Krut'ko VN.

Living 100 Monogr. 2017 Jan;2017(1B). pii: https://www.soa.org/Library/Monographs/Life/Living-To-100/2017/table-of-contents.aspx. Epub 2017 Jul 27.

PMID: 29170765

Abstract

Knowledge of future mortality levels and trends is important for actuarial practice but poses a challenge to actuaries and demographers. The Lee-Carter method, currently used for mortality forecasting, is based on the assumption that the historical evolution of mortality at all age groups is driven by one factor only. This approach cannot capture an additive manner of mortality decline observed before the 1960s. To overcome the limitation of the one-factor model of mortality and to determine the true number of factors underlying mortality changes over time, we suggest a new approach to mortality analysis and forecasting based on the method of latent variable analysis. The basic assumption of this approach is that most variation in mortality rates over time is a manifestation of a small number of latent variables, variation in which gives rise to the observed mortality patterns. To extract major components of mortality variation, we apply factor analysis to mortality changes in developed countries over the period of 1900-2014. Factor analysis of time series of age-specific death rates in 12 developed countries (data taken from the Human Mortality Database) identified two factors capable of explaining almost 94 to 99 percent of the variance in the temporal changes of adult death rates at ages 25 to 85 years. Analysis of these two factors reveals that the first factor is a "young-age" or background factor with high factor loadings at ages 30 to 45 years. The second factor can be called an "oldage" or senescent factor because of high factor loadings at ages 65 to 85 years. It was found that the senescent factor was relatively stable in the past but now is rapidly declining for both men and women. The decline of the senescent factor is faster for men, although in most countries, it started almost 30 years later. Factor analysis of time series of age-specific death rates conducted for the oldest-old ages (65 to 100 years) found two factors explaining variation of mortality at extremely old ages in the United States. The first factor is comparable to the senescent factor found for adult mortality. The second factor, however, is specific to extreme old ages (96 to 100 years) and shows peaks in 1960 and 2000. Although mortality below 90 to 95 years shows a steady decline with time driven by the senescent factor, mortality of centenarians does not decline and remains relatively stable. The approach suggested in this paper has several advantages. First, it is able to determine the total number of independent factors affecting mortality changes over time. Second, this approach allows researchers to determine the time interval in which underlying factors remain stable or undergo rapid changes. Most methods of mortality projections are not able to identify the best base period for mortality projections, attempting to use the longest-possible time period instead. We observe that the senescent factor of mortality continues to decline, and this decline does not demonstrate any indications of slowing down. At the same time, mortality of centenarians does not decline and remains stable. The lack of mortality decline at extremely old ages may diminish anticipated longevity gains in the future.

 

[The below paper is pdf-availed.]

Association of Mortality with Ocular Diseases and Visual Impairment in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report Number 13.

Age-Related Eye Disease Study 2 Research Group, Papudesu C, Clemons TE, Agrón E, Chew EY.

Ophthalmology. 2017 Nov 16. pii: S0161-6420(17)32553-8. doi: 10.1016/j.ophtha.2017.10.028. [Epub ahead of print]

PMID: 29153456

Abstract

PURPOSE:

To evaluate the association of mortality with visual acuity (VA) impairment, age-related macular degeneration (AMD), and cataract surgery.

DESIGN:

Cohort study.

PARTICIPANTS:

Participants with at least intermediate AMD enrolled in a randomized controlled clinical trial of lutein/zeaxanthin and/or omega-3 fatty acids, the Age-Related Eye Disease Study 2 (AREDS2), for treatment of AMD and cataract.

METHODS:

Baseline and annual eye examinations included best-corrected visual acuity (BCVA) assessments, slit-lamp examinations, and stereoscopic fundus photographs that were centrally graded for development of late AMD (central geographic atrophy or neovascular AMD) or pseudophakia. Cause-specific mortality was determined on the basis of the International Classification of Diseases 9th or 10th Revision codes. Risk of all-cause and cause-specific mortality was assessed with Cox proportional hazards models adjusted for age, sex, AMD severity, VA, history of cataract surgery, and assigned AREDS2 study treatment. Analyses included baseline covariates: race, education, smoking status, diabetes, and cardiovascular disease.

RESULTS:

During follow-up (median 5 years), 368 (9%) of the 4203 AREDS2 participants died. Participants with neovascular AMD in 1 eye at baseline had a statistically significant increased risk for mortality compared with participants with no or few drusen (hazard ratio {HR}, 1.56; 95% confidence interval [CI], 1.21-2.01; P < 0.001). Poorer survival was associated with bilateral cataract surgery before enrollment compared with baseline bilateral phakia (HR, 1.63; 95% CI, 1.29-2.07; P < 0.001) and with BCVA of less than 20/40 compared with participants with 20/40 or better (HR, 1.56; 95% CI, 1.06-2.30; P = 0.024), adjusted for age, sex, and statistically significant covariates. Participants who received antivascular endothelial growth factor therapies for neovascular AMD had decreased mortality compared with those who did not (HR, 0.71; 95% CI, 0.57-0.88; P = 0.002). The association between all-cause mortality and AREDS2 treatment whether assessing the main or individual treatment effect was not significantly different (omega-3 fatty acids main effect HR, 1.18; 95% CI, 0.96-1.45; P = 0.12; lutein/zeaxanthin main effect HR, 1.04; 95% CI, 0.85-1.28; P = 0.71).

CONCLUSIONS:

In AREDS2, the presence of late AMD, bilateral cataract surgery, and VA less than 20/40 was associated with decreased survival. However, oral supplementation with omega-3 fatty acids, lutein plus zeaxanthin, zinc, or beta-carotene had no statistically significant impact on mortality.

 

Coffee Consumption and Lung Cancer Risk: The Japan Public Health Center-Based Prospective Study.

Narita S, Saito E, Sawada N, Shimazu T, Yamaji T, Iwasaki M, Sasazuki S, Noda M, Inoue M, Tsugane S.

J Epidemiol. 2017 Nov 18. doi: 10.2188/jea.JE20160191. [Epub ahead of print]

PMID: 29151475

https://www.jstage.jst.go.jp/article/jea/advpub/0/advpub_JE20160191/_pdf/-char/en

Abstract

BACKGROUND:

Many epidemiological studies have indicated a positive association between coffee intake and lung cancer risk, but such findings were suggested to be confounded by smoking. Furthermore, only a few of these studies have been conducted in Asia. Here, we investigated the association between coffee intake and lung cancer risk in one of the largest prospective cohort studies in Japan.

METHODS:

We investigated the association of coffee drinking and subsequent incidence of lung cancer among 41,727 men and 45,352 women in the Japan Public Health Center-based Prospective Study using Cox proportional hazards regression, with adjustment for potential confounders and by strata of smoking status. Coffee and other dietary intakes were assessed once at baseline with a food frequency questionnaire (FFQ).

RESULTS:

During 1,481,887 person-years of follow-up between 1990 and 2011, a total of 1,668 lung cancer cases were identified. In a multivariate regression model, coffee consumption was not associated with risk of lung cancer (HR 1.16; 95% CI, 0.82-1.63; Ptrend = 0.285 for men and HR 1.49; 95% CI, 0.79-2.83; Ptrend = 0.942 for women). However, there was a significant increase in the risk for small cell carcinoma (HR 3.52; 95% CI, 1.49-8.28; Ptrend < 0.001).

CONCLUSION:

Our prospective study suggests that habitual consumption of coffee is not associated with an increased risk of lung cancer incidence, despite observing a significant increase in the risk for small cell carcinoma.

KEYWORDS:

Japan Public Health Center-based Prospective (JPHC) Study; coffee; lung cancer

 

[The below paper is pdf-availed.]

The effect of viscous soluble fiber on blood pressure: A systematic review and meta-analysis of randomized controlled trials.

Khan K, Jovanovski E, Ho HVT, Marques ACR, Zurbau A, Mejia SB, Sievenpiper JL, Vuksan V.

Nutr Metab Cardiovasc Dis. 2017 Oct 7. pii: S0939-4753(17)30222-3. doi: 10.1016/j.numecd.2017.09.007. [Epub ahead of print]

PMID: 29153856

Abstract

AIMS:

Dietary fiber intake, especially viscous soluble fiber, has been established as a means to reduce cardiometabolic risk factors. Whether this is true for blood pressure remains controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effects of viscous soluble fiber supplementation on blood pressure and quantify the effect of individual fibers.

DATA SYNTHESIS:

MEDLINE, Embase, and Cochrane databases were searched. We included RCTs of ≥4-weeks in duration assessing viscous fiber supplementation from five types: β-glucan from oats and barley, guar gum, konjac, pectin and psyllium, on systolic blood pressure (SBP) and diastolic blood pressure (DBP). Study data were pooled using the generic inverse variance method with random effects models and expressed as mean differences (MD) with 95% confidence intervals (CIs). Twenty-two (N = 1430) and twenty-one RCTs (N = 1343) were included in the final analysis for SBP and DBP, respectively. Viscous fiber reduced SBP (MD = -1.59 mmHg [95% CI: -2.72,-0.46]) and DBP (MD = -0.39 mmHg [95% CI: -0.76,-0.01]) at a median dose of 8.7 g/day (1.45-30 g/day) over a median follow-up of 7-weeks. Substantial heterogeneity in SBP (I2 = 72%, P < 0.01) and DBP (I2 = 67%, P < 0.01) analysis occurred. Within the five fiber types, SBP reductions were observed only for supplementation using psyllium fiber (MD = -2.39 mmHg [95% CI: -4.62,-0.17]).

CONCLUSION:

Viscous soluble fiber has an overall lowering effect on SBP and DBP. Inclusion of viscous fiber to habitual diets may have additional value in reducing CVD risk via improvement in blood pressure.

PROTOCOL REGISTRATION:

ClinicalTrials.gov identifier-NCT02670967.

KEYWORDS:

Blood pressure; Guar gum; Konjac; Meta-analysis; Pectin; Psyllium; Viscous soluble fiber; β-Glucan

 

[The below paper is not pdf-availed.]

Dietary Sodium Modifies Serum Uric Acid Concentrations in Humans.

Todd AS, Walker RJ, MacGinley RJ, Kelly J, Merriman TR, Major TJ, Johnson RJ.

Am J Hypertens. 2017 Nov 6;30(12):1196-1202. doi: 10.1093/ajh/hpx123.

PMID: 28985270

http://sci-hub.cc/10.1093/ajh/hpx123

Abstract

BACKGROUND:

Subjects with hypertension are frequently obese or insulin resistant, both conditions in which hyperuricemia is common. Obese and insulin-resistant subjects are also known to have blood pressure that is more sensitive to changes in dietary sodium intake. Whether hyperuricemia is a resulting consequence, moderating or contributing factor to the development of hypertension has not been fully evaluated and very few studies have reported interactions between sodium intake and serum uric acid.

METHODS:

We performed further analysis of our randomized controlled clinical trials (Australian New Zealand Clinical Trials Registry #12609000161224 and #12609000292279) designed to assess the effects of modifying sodium intake on concentrations of serum markers, including uric acid. Uric acid and other variables (including blood pressure, renin, and aldosterone) were measured at baseline and 4 weeks following the commencement of low (60 mmol/day), moderate (150 mmol/day), and high (200-250 mmol/day) dietary sodium intake.

RESULTS:

The median aldosterone-to-renin ratio was 1.90 [pg/ml]/[pg/ml] (range 0.10-11.04). Serum uric acid fell significantly in both the moderate and high interventions compared to the low sodium intervention. This pattern of response occurred when all subjects were analyzed, and when normotensive or hypertensive subjects were analyzed alone.

CONCLUSIONS:

Although previously reported in hypertensive subjects, these data provide evidence in normotensive subjects of an interaction between dietary sodium intake and serum uric acid. As this interaction is present in the absence of hypertension, it is possible it could play a role in hypertension development, and will need to be considered in future trials of dietary sodium intake.

KEYWORDS:

blood pressure; hypertension; sodium; urate; uric acid

Edited by AlPater

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[All but the first and last indicated below papers are OPEN ACCESS.]

Why do we age? Insights into biology and evolution of ageing.

Weinkove D, Goljanek-Whysall K.

Biogerontology. 2017 Dec;18(6):855-857. doi: 10.1007/s10522-017-9734-4. Epub 2017 Oct 31. No abstract available.

PMID: 29086101

https://sci-hub.cc/http://link.springer.com/10.1007/s10522-017-9734-4

>>>>>>>>>>>>>>>>>>>>>>>>

Biogerontology. Volume 18 Number 6

December 2017, Issue 6, Pages 855-971

BSRA Special Issue: Biology and Evolution of Ageing

https://link.springer.com/journal/10522/18/6/page/1

In this issue (9 articles)

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Lipid (per) oxidation in mitochondria: an emerging target in the ageing process?

Ademowo OS, Dias HKI, Burton DGA, Griffiths HR.

Biogerontology. 2017 Dec;18(6):859-879. doi: 10.1007/s10522-017-9710-z. Epub 2017 May 24. Review.

PMID: 28540446

https://link.springer.com/article/10.1007%2Fs10522-017-9710-z

Abstract

Lipids are essential for physiological processes such as maintaining membrane integrity, providing a source of energy and acting as signalling molecules to control processes including cell proliferation, metabolism, inflammation and apoptosis. Disruption of lipid homeostasis can promote pathological changes that contribute towards biological ageing and age-related diseases. Several age-related diseases have been associated with altered lipid metabolism and an elevation in highly damaging lipid peroxidation products; the latter has been ascribed, at least in part, to mitochondrial dysfunction and elevated ROS formation. In addition, senescent cells, which are known to contribute significantly to age-related pathologies, are also associated with impaired mitochondrial function and changes in lipid metabolism. Therapeutic targeting of dysfunctional mitochondrial and pathological lipid metabolism is an emerging strategy for alleviating their negative impact during ageing and the progression to age-related diseases. Such therapies could include the use of drugs that prevent mitochondrial uncoupling, inhibit inflammatory lipid synthesis, modulate lipid transport or storage, reduce mitochondrial oxidative stress and eliminate senescent cells from tissues. In this review, we provide an overview of lipid structure and function, with emphasis on mitochondrial lipids and their potential for therapeutic targeting during ageing and age-related disease.

KEYWORDS:

Ageing; Antioxidant; Cellular senescence; Fatty acid; Membrane lipid remodelling; Mitochondria; Oxidised phospholipid

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Twelve weeks’ progressive resistance training combined with protein supplementation beyond habitual intakes increases upper leg lean tissue mass, muscle strength and extended gait speed in healthy older women

Peter Francis, William Mc Cormack, Clodagh Toomey, Catherine Norton… Pages 881-891

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Early nutrition and ageing: can we intervene?

Duque-Guimarães D, Ozanne S.

Biogerontology. 2017 Dec;18(6):893-900. doi: 10.1007/s10522-017-9691-y. Epub 2017 Mar 29.

PMID: 28357523

https://link.springer.com/article/10.1007%2Fs10522-017-9691-y

Abstract

Ageing, a complex process that results in progressive decline in intrinsic physiological function leading to an increase in mortality rate, has been shown to be affected by early life nutrition. Accumulating data from animal and epidemiological studies indicate that exposure to a suboptimal nutritional environment during fetal life can have long-term effects on adult health. In this paper, we discuss the impact of early life nutrition on the development of age-associated diseases and life span. Special emphasis is given to studies that have investigated the molecular mechanisms underlying these effects. These include permanent structural and cellular changes including epigenetics modifications, oxidative stress, DNA damage and telomere shortening. Potential strategies targeting these mechanisms, in order to prevent or alleviate the detrimental effects of suboptimal early nutrition on lifespan and age-related diseases, are also discussed. Although recent reports have already identified effective therapeutic interventions, such as antioxidant supplementation, further understanding of the extent and nature of how early nutrition influences the ageing process will enable the development of novel and more effective approaches to improve health and extend human lifespan in the future.

KEYWORDS:

Ageing; Early nutrition; Fetal programming; Intervention; Lifespan

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Measurement of muscle health in aging.

Francis P, Lyons M, Piasecki M, Mc Phee J, Hind K, Jakeman P.

Biogerontology. 2017 Dec;18(6):901-911. doi: 10.1007/s10522-017-9697-5. Epub 2017 Apr 4.

PMID: 28378095

https://link.springer.com/article/10.1007%2Fs10522-017-9697-5

Abstract

Muscle health is a critical component in the struggle against physical frailty and the efforts to maintain metabolic health until the limit of chronological age. Consensus opinion is to evaluate muscle health in terms of muscle mass, strength and functional capability. There has been considerable variability in the components of muscle health which have been investigated in addition to variability in the tools of assessment and protocol for measurement. This is in stark contrast to the validated measurement of bone health across the adult life span. The purpose of this review was to identify indices of muscle mass, strength and functional capability most responsive to change with ageing and where possible to provide an estimate of the rate of change. We suggest lean tissue mass (LTM) or skeletal muscle (SM) is best evaluated from the thigh region due to its greater responsiveness to ageing compared to the whole body. The anterior compartment of the thigh region undergoes a preferential age-related decline in SM and force generating capacity. Therefore, we suggest that knee extensor torque is measured to represent the force generating capacity of the thigh and subsequently, to express muscle quality (strength per unit tissue). Finally, we suggest measures of functional capability which allow participants perform to a greater maximum are most appropriate to track age-related difference in functional capacity across the adult lifespan. This is due to their ability encompass a broad spectrum of abilities. This review suggests indices of muscular health for which reference ranges can be generated across the lifespan.

KEYWORDS:

Functional capability; Healthy aging; Muscle strength; Sarcopenia

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Growth factor, energy and nutrient sensing signalling pathways in metabolic ageing.

Bettedi L, Foukas LC.

Biogerontology. 2017 Dec;18(6):913-929. doi: 10.1007/s10522-017-9724-6. Epub 2017 Aug 9.

PMID: 28795262

https://link.springer.com/article/10.1007%2Fs10522-017-9724-6

Abstract

The field of the biology of ageing has received increasing attention from a biomedical point of view over the past decades. The main reason has been the realisation that increases in human population life expectancy are accompanied by late onset diseases. Indeed, ageing is the most important risk factor for a number of neoplastic, neurodegenerative and metabolic pathologies. Advances in the knowledge of the genetics of ageing, mainly through research in model organisms, have implicated various cellular processes and the respective signalling pathways that regulate them in cellular and organismal ageing. Associated with ageing is a dysregulation of metabolic homeostasis usually manifested as age-related obesity, diminished insulin sensitivity and impaired glucose and lipid homeostasis. Metabolic deterioration contributes to the ageing phenotype and metabolic pathologies are thought to be one of the main factors limiting the potential for lifespan extension. Great efforts have been directed towards identifying pharmacological interventions with the potential to improve healthspan and a number of natural and synthetic compounds have shown promise in achieving beneficial metabolic effects.

KEYWORDS:

Ageing; Diabetes; Insulin resistance; Metabolism; Obesity; PI3K

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Exercise and bone health across the lifespan.

Santos L, Elliott-Sale KJ, Sale C.

Biogerontology. 2017 Dec;18(6):931-946. doi: 10.1007/s10522-017-9732-6. Epub 2017 Oct 20.

PMID: 29052784

https://link.springer.com/article/10.1007%2Fs10522-017-9732-6

Abstract

With ageing, bone tissue undergoes significant compositional, architectural and metabolic alterations potentially leading to osteoporosis. Osteoporosis is the most prevalent bone disorder, which is characterised by progressive bone weakening and an increased risk of fragility fractures. Although this metabolic disease is conventionally associated with ageing and menopause, the predisposing factors are thought to be established during childhood and adolescence. In light of this, exercise interventions implemented during maturation are likely to be highly beneficial as part of a long-term strategy to maximise peak bone mass and hence delay the onset of age- or menopause-related osteoporosis. This notion is supported by data on exercise interventions implemented during childhood and adolescence, which confirmed that weight-bearing activity, particularly if undertaken during peripubertal development, is capable of generating a significant osteogenic response leading to bone anabolism. Recent work on human ageing and epigenetics suggests that undertaking exercise after the fourth decade of life is still important, given the anti-ageing effect and health benefits provided, potentially occurring via a delay in telomere shortening and modification of DNA methylation patterns associated with ageing. Exercise is among the primary modifiable factors capable of influencing bone health by preserving bone mass and strength, preventing the death of bone cells and anti-ageing action provided.

KEYWORDS:

Bone adaptation; Bone ageing; Bone health; Exercise; Lifespan; Osteoporosis

 

Physical activity and calorie intake mediate the relationship from depression to body fat mass among female Mexican health workers.

Quezada AD, Macías-Waldman N, Salmerón J, Swigart T, Gallegos-Carrillo K.

Int J Behav Nutr Phys Act. 2017 Nov 17;14(1):160. doi: 10.1186/s12966-017-0612-x.

PMID: 29149890

https://ijbnpa.biomedcentral.com/articles/10.1186/s12966-017-0612-x

https://ijbnpa.biomedcentral.com/track/pdf/10.1186/s12966-017-0612-x?site=ijbnpa.biomedcentral.com

Abstract

BACKGROUND:

Depression is a foremost cause of morbidity throughout the world and the prevalence of depression in women is about twice as high as men. Additionally, overweight and obesity are major global health concerns. We explored the relationship between depression and body fat, and the role of physical activity and diet as mediators of this relationship in a sample of 456 adult female Mexican health workers.

METHOD:

Longitudinal and cross-sectional analyses using data from adult women of the Health Workers Cohort Study (HWCS) Measures of body fat mass (kg from DEXA), dietary intake (kcal from FFQ), leisure time activity (METs/wk) and depression (CES-D) were determined in two waves (2004-2006 and 2010-2011). We explored the interrelation between body fat, diet, leisure time, physical activity, and depression using a cross-lagged effects model fitted to longitudinal data. We also fitted a structural equations model to cross-sectional data with body fat as the main outcome, and dietary intake and physical activity from leisure time as mediators between depression and body fat.

RESULTS:

Baseline depression was significantly related to higher depression, higher calorie intake, and lower leisure time physical activity at follow-up. From our cross-sectional model, each standard deviation increase in the depression score was associated with an average increase of 751 ± 259 g (± standard error) in body fat through the mediating effects of calorie intake and physical activity.

CONCLUSIONS:

The results of this study show how depression may influence energy imbalance between calories consumed and calories expended, resulting in higher body fat among those with a greater depression score. Evaluating the role of mental conditions like depression in dietary and physical activity behaviors should be positioned as a key research goal for better designed and targeted public health interventions.

KEYWORDS:

Depression; Mexico; Physical activity; Women

 

[The below paper is pdf-availed.]

Exploring the path between depression, anxiety and 10-year cardiovascular disease incidence, among apparently healthy Greek middle-aged adults: The ATTICA study.

Kollia N, Panagiotakos D, Georgousopoulou E, Chrysohoou C, Yannakoulia M, Stefanadis C, Chatterji S, Haro JM, Papageorgiou C, Pitsavos C; ATTICA Study investigators.

Maturitas. 2017 Dec;106:73-79. doi: 10.1016/j.maturitas.2017.09.005. Epub 2017 Sep 20.

PMID: 29150168

Abstract

OBJECTIVES:

Although there is substantial evidence that psychological factors play an important role in the onset and course of cardiovascular disease (CVD), less is known about their combined effect and the pathways by which they affect cardiovascular health. The present work aimed to prospectively explore the effects of depression and anxiety on the 10-year CVD incidence, in relation to other lifestyle determinants, as linking factors in the context of the ATTICA study. Study design/Main outcome measures: The ATTICA study is a population-based, health and nutrition prospective cohort study (2002-2012), during which 853 middle-aged participants without a history of CVD [453 men (aged 45±13years) and 400 women (aged 44±18years)], underwent psychological evaluations at enrollment. The latent trait of depression and anxiety combined measure was estimated and referred as "Psychological distress"; path analysis was applied to describe the relationships among the different factors.

RESULTS:

"Psychological distress" was positively associated with the 10-year CVD incidence (adjusted OR per 10 units: 1.4, 95% CI: 1.1, 1.7). Three linking pathways were revealed: sedentariness, inflammation and metabolic syndrome. Moreover, "Psychological distress" mediated the association between socioeconomic status (SES) and CVD, with participants of low SES scoring higher on the psychological measure (adjusted linear regression coefficient b: -7.1, 95% CI: -9.7, -4.5).

CONCLUSIONS:

Lifestyle and clinical factors seem to link psychological distress with CVD development. Joint psychological assessments should be considered for inclusion in CVD preventive strategies, which should incorporate interventions for interrupting the linking pathways.

KEYWORDS:

Anxiety; CVD risk factors; Cardiovascular disease; Depression; Mediation; Psychological distress

 

Change in hydration indices associated with an increase in total water intake of more than 0.5 L/day, sustained over 4 weeks, in healthy young men with initial total water intake below 2 L/day.

Stookey JD, Hamer J, Killilea DW.

Physiol Rep. 2017 Nov;5(22). pii: e13356. doi: 10.14814/phy2.13356.

PMID: 29150589

http://physreports.physiology.org/content/5/22/e13356

http://onlinelibrary.wiley.com/doi/10.14814/phy2.13356/pdf

Abstract

This secondary data analysis addressed gaps in knowledge about effects of chronic water intake. Longitudinal data from the Adapt Study were used to describe effects of prescribing a sustained increase in water intake relative to baseline, for 4 weeks, on multiple indices of total body water (TBW) flux, regulation, distribution, and volume in five healthy, free-living, young men, with mean total water intake initially below 2 L/day. Indices were measured weekly. Within-person fixed effect models tested for significant changes in indices over time and associations between changes in indices. Agreement between indices was described. Mixed models tested if baseline between-person differences in hydration indices modified changes in indices over time. Body water flux: The half-life of water in the body decreased significantly. Body water regulation: Serum osmolality decreased significantly. Urine anti-diuretic hormone, sodium, potassium, and osmolality decreased significantly. Plasma aldosterone and serum sodium increased significantly. Body water distribution: No significant changes were observed. Body water volume: Saliva osmolality decreased significantly. Body weight increased significantly by a mean ± SEM of 1.8% ± 0.5% from baseline over 4 weeks. Changes in indices were significantly inter-correlated. Agreement between indices changed over 4 weeks. Baseline saliva osmolality significantly modified responses to chronic water intake. The results motivate hypotheses for future studies: Chronic TBW deficit occurs in healthy individuals under daily life conditions and increases chronic disease risk; Sustained higher water intake restores TBW through gradual isotonic retention of potassium and/or sodium; Saliva osmolality is a sensitive and specific index of chronic hydration status.

KEYWORDS:

Biomarker; Healthy adults; Hydration; Water intake

 

Scientists rejuvenate old human cells, make them look and act younger

"Far more research is needed now to establish the true potential for these sort of approaches to address the degenerative effects of aging," said researcher Lorna Harries.

By Brooks Hays | Nov. 7, 2017

https://www.upi.com/Health_News/2017/11/07/Scientists-rejuvenate-old-human-cells-make-them-look-and-act-younger/4541510076280/

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Small molecule modulation of splicing factor expression is associated with rescue from cellular senescence.

Latorre E, Birar VC, Sheerin AN, Jeynes JCC, Hooper A, Dawe HR, Melzer D, Cox LS, Faragher RGA, Ostler EL, Harries LW.

BMC Cell Biol. 2017 Oct 17;18(1):31. doi: 10.1186/s12860-017-0147-7.

PMID: 29041897 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645932/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645932/pdf/12860_2017_Article_147.pdf

Abstract

BACKGROUND:

Altered expression of mRNA splicing factors occurs with ageing in vivo and is thought to be an ageing mechanism. The accumulation of senescent cells also occurs in vivo with advancing age and causes much degenerative age-related pathology. However, the relationship between these two processes is opaque. Accordingly we developed a novel panel of small molecules based on resveratrol, previously suggested to alter mRNA splicing, to determine whether altered splicing factor expression had potential to influence features of replicative senescence.

RESULTS:

Treatment with resveralogues was associated with altered splicing factor expression and rescue of multiple features of senescence. This rescue was independent of cell cycle traverse and also independent of SIRT1, SASP modulation or senolysis. Under growth permissive conditions, cells demonstrating restored splicing factor expression also demonstrated increased telomere length, re-entered cell cycle and resumed proliferation. These phenomena were also influenced by ERK antagonists and agonists.

CONCLUSIONS:

This is the first demonstration that moderation of splicing factor levels is associated with reversal of cellular senescence in human primary fibroblasts. Small molecule modulators of such targets may therefore represent promising novel anti-degenerative therapies.

KEYWORDS:

Ageing; Alternative splicing; Fibroblasts; Resveratrol; Senescence

 

The risk factors of 9-year follow-up on hypertension in middle-aged people in Tujia-Nationality settlement of China.

Liu X, Liu C, Schenck H, Yi X, Wang H, Shi X.

J Hum Hypertens. 2017 Dec;31(12):838-842. doi: 10.1038/jhh.2017.58. Epub 2017 Aug 10.

PMID: 28795685 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680414/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680414/pdf/jhh201758a.pdf

Abstract

The aim of this study was to investigate the risk factors of hypertension in middle-aged people within the Tujia-Nationality settlement in China. Demographics questionnaires and fitness tests were performed to identify the risk factors of hypertension in middle-aged people in the years 2005, 2010 and 2014 in the area of southwest Hubei of China. Of the 2428 participants, 568 were classified as hypertensive, giving an overall occurrence of hypertension at 23.4%, and the prevalence of hypertension was the highest in the year 2014 (34.9%). Furthermore, Tujia minority had a significantly higher risk for having hypertension (odds ratio=1.055 with 95% confidence interval (CI): 1.039-1.072; P=0.001) than Han people. Individuals with the lowest level of cardiorespiratory fitness (CRF) had a 2.483-fold risk for hypertension (95% CI, 1.530-4.031; P=0.001). Obesity and overweight individuals increased the risk by 3.470-fold and 2.124-fold, respectively, for having hypertension compared to normal weight people. Finally, white-collar workers had a 58.1 and 31.8% higher risk for hypertension than blue-collar workers in rural and urban areas, respectively. These results demonstrated that the prevalence of hypertension was higher between 2011 and 2014 in the area. The main risk factors for developing hypertension were found to be sex (as woman), Tujia minority, white-collar workers, overweight-obese, those with a middle school education, and those with the lowest CRF.

 

[The below paper is not pdf-availed.]

The relationship between physical activity, obesity, and lung cancer risk by smoking status in a large prospective cohort of US adults.

Patel AV, Carter BD, Stevens VL, Gaudet MM, Campbell PT, Gapstur SM.

Cancer Causes Control. 2017 Dec;28(12):1357-1368. doi: 10.1007/s10552-017-0949-0. Epub 2017 Sep 22.

PMID: 28940119

Abstract

Physical activity has been associated with lower lung cancer risk in numerous studies with estimates ranging from 20 to 50% lower risk in the most versus the least active study participants. Underweight and obesity have also been associated with lower lung cancer risk, with a nonlinear, inverted U-shaped relationship. However, associations of physical activity and obesity with lung cancer are likely significantly confounded by smoking since individuals who smoke are generally less active and leaner than non-smokers, but few studies have examined these associations stratified by smoking status. Using data from 162,679 men and women who were cancer-free at enrollment (1992-1993) in the American Cancer Society Cancer Prevention Study-II Nutrition Cohort, we examined associations of baseline recreational physical activity (MET-hours per week; none, 0.1 to <8.75 (reference), 8.75-17.4, 17.5+ MET-hours/week), baseline body mass index (BMI, weight (kg)/height (m2); <18.5, 18.5-22.0 (reference), 22.1-24.9, 25.0-29.9, 30.0+ kg/m2), and waist circumference (measured in 1997; sex-specific quartiles) in relation to lung cancer risk stratified by smoking status and years since quitting among former smokers (never, current, former <10 years, former, 10-19 years, former 20+ years). Cox proportional hazards modeling computed hazard rate ratios (RR) and 95% confidence intervals (CI) while adjusting for potential confounders. During 2,384,546 person years of follow-up time, 4,669 men and women were diagnosed with lung cancer (453 among never smokers; 1,452 among current smokers; 1,194 among former smokers <10 years since quitting; 725 among former 10-19 years; and 845 among former 20+ years). Physical activity was not associated with lung cancer risk within any of the smoking strata except in former smokers less than 10 years since quitting (RR = 0.77; 95% CI 0.67-0.90 for 17.5+ MET-hours/week). Similarly, BMI was inversely associated with lung cancer in former smokers less than 10 years since quitting (RR = 0.68; 95% CI 0.55-0.84 for 30+ kg/m2) and more modestly in former smokers who quit 10-19 and 20+ years ago. Waist circumference was not associated with lung cancer risk in any smoking category. While being physically active and maintaining a healthy body weight are important for prevention of various chronic diseases, including several types of cancer, our results suggest that physical activity, BMI, and waist circumference are not associated with lung cancer risk, regardless of smoking status.

KEYWORDS:

Lung cancer; Obesity; Physical activity; Prospective cohort

 

Association of Family History of Exceptional Longevity With Decline in Physical Function in Aging.

Ayers E, Barzilai N, Crandall JP, Milman S, Verghese J.

J Gerontol A Biol Sci Med Sci. 2017 Nov 9;72(12):1649-1655. doi: 10.1093/gerona/glx053.

PMID: 28379407

https://watermark.silverchair.com/glx053.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAcMwggG_BgkqhkiG9w0BBwagggGwMIIBrAIBADCCAaUGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM3ne0kU_PqAc_VdKaAgEQgIIBdoYvOplW3fOFlkl6RW7I4ZEznXGzwqZOVeaB9s4c5v6PkDGZIvUmEV5obl8R95bublkANKmC4sDRxtlKPC1AwW9DuyOo9sTRJpQqclo5ysrQz67L3_aU43FzSFqp98lzMOB7MwcYAvxby6axu-8kFhx4fC06lV0mTV-OncAhd0RHChtc-x6Af2PfBqVk6eUMEDflviqL_fPw0pwEZ1adRdhdOuJzKhXdsfIpodlYJWzsyZN8kD9D612lOnEveoIZ9UA2DRIRfL5OzIxiQ4r0zITOuPklXO1hatkd3IIT_MJMvMoYnvKYGAhpszVaUUGFFRU2AQjWmxB77UVUi9zV98psT0pnbxUlOf_T3ebknuQ8Ju1QK-adiqstO_I5sWpZvWSmV5ncxJCj1srgz2lFuKSa76KpPctCAPZtAb0dkbq-yHxY9d13eU3LJtVddeTp7b1if5ELtGtVoG7qXPJLRvinr9krL55qaeswvpMmLkrLg61DCKZM

Abstract

BACKGROUND:

Although many genetic and nongenetic factors interact to determine an individual's physical phenotype, there has been limited examination of the contribution of family history of exceptional parental longevity on decline in physical function in aging.

METHODS:

The LonGenity study recruited a relatively genetically homogenous cohort of Ashkenazi Jewish adults age 65 and older, who were defined as either offspring of parents with exceptional longevity ([OPEL]: having at least one parent who lived to age 95 or older) or offspring of parents with usual survival ([OPUS]: neither parent survived to age 95). Decline in performance on objective measures of strength (grip strength), balance (unipedal stance), and mobility (gait speed) as well as a composite physical function measure, the Short physical performance battery (SPPB), were compared between the two groups over a median follow-up of 3.2 years, accounting for age, sex, education, and comorbidities.

RESULTS:

Of the 984 LonGenity participants (mean age 76, 55% women), 448 were OPEL and 536 were OPUS. Compared to OPUS, OPEL had slower decline on measures of unipedal stance (-0.03 log-units/year, p = .026), repeated chair rise (0.13 s/year, p = .020) and SPPB (-0.11 points/year, p = .002). OPEL women had slower decline on chair rise and SPPB scores compared to OPUS women, although OPEL men had slower decline on unipedal stance compared to OPUS men.

CONCLUSION:

Our findings provide evidence that variation in late-life decline in physical function is associated with familial longevity, and may vary for men and women.

KEYWORDS:

Genotypes; Phenotypes; Physical function; Successful aging

 

[The below paper should be pdf-availed via our library but it said the check later.]

Age-Related Biomarkers in LLFS Families With Exceptional Cognitive Abilities.

Barral S, Singh J, Fagan E, Cosentino S, Andersen-Toomey SL, Wojczynski MK, Feitosa M, Kammerer CM, Schupf N; Long Life Family Study.

J Gerontol A Biol Sci Med Sci. 2017 Nov 9;72(12):1683-1688. doi: 10.1093/gerona/glx034.

PMID: 28329324

Abstract

BACKGROUND:

We previously demonstrated familial aggregation of memory performance within the Long Life Family Study (LLFS), suggesting that exceptional cognition (EC) may contribute to their exceptional longevity. Here, we investigated whether LLFS families with EC may also exhibit more favorable profiles of other age-related biomarkers.

METHODS:

Nondemented offspring of the LLFS probands scoring 1.5 SD above the mean in a cognitive phenotype were classified as participants with EC. Families were categorized into EC (n = 28) and non-EC families (n = 433) based on having at least two EC offspring. Adjusted general estimating equations were used to investigate whether EC families had a better longevity and age-related biomarker profiles than non-EC families.

RESULTS:

EC families exhibited higher scores on familial longevity than non-EC families (average Family Longevity Selection Score of 12 ± 7 vs 9 ± 8, p = 2.5 × 10-14). EC families showed a better a metabolic profile (β = -0.63, SE = 0.23, p = .006) than non-EC families. The healthier metabolic profile is related to obesity in an age-dependent fashion. The prevalence of obesity in EC families is significantly lower compared with non-EC families (38% vs 51%, p = .015) among family members less than 80 years of age; however, among EC family members 80 years of age and older, the prevalence of obesity is higher (40% vs 38%, p = .011). EC families also showed better physical/pulmonary function than non-EC families (β = 0.51, SE = 0.25, p = .042).

CONCLUSIONS:

Long-live families with EC are characterized by a healthier metabolic profile which is related to the prevalence of obesity in the older family members. Our results suggest that familial exceptional longevity may be achieved through heterogeneous yet correlated pathways.

KEYWORDS:

Age-related biomarkers; Exceptional cognition; Exceptional longevity

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A systematic review of the effect of dietary saturated and polyunsaturated fat on heart disease.

Clifton PM, Keogh JB.

Nutr Metab Cardiovasc Dis. 2017 Oct 18. pii: S0939-4753(17)30237-5. doi: 10.1016/j.numecd.2017.10.010. [Epub ahead of print]

PMID: 29174025

Abstract

AIMS:

Over the last 7 years there has been intense debate about the advice to reduce saturated fat and increase polyunsaturated fat to reduce CVD risk. The aim of this review was to examine systematic reviews and meta-analyses since 2010 on this topic plus additional cohort studies and interventions not included in these reviews.

DATA SYNTHESIS:

High saturated and trans fat intake (which elevates LDL like saturated fat) in the Nurses and Health Professional Follow-Up Studies combined is associated with an 8-13% higher mortality and replacement of saturated fat with any carbohydrate, PUFA and MUFA is associated with lower mortality with PUFA being more effective than MUFA (19% reduction versus 11%). With CVD mortality only PUFA and fish oil replacement of saturated fat lowers risk with a 28% reduction in CVD mortality per 5% of energy. Replacing saturated fat with PUFA or MUFA is equally effective at reducing CHD events and replacement with whole grains will lower events while replacement with sugar and starch increases events. Replacement of saturated fat with carbohydrate has no effect on CHD events or death. Only PUFA replacement of saturated fat lowers CHD events and CVD and total mortality. Replacing saturated fat with linoleic acid appears to be beneficial based on the Hooper Cochrane meta-analysis of interventions although other analyses with fewer studies have shown no effect.

CONCLUSIONS:

Reducing saturated fat and replacing it with carbohydrate will not lower CHD events or CVD mortality although it will reduce total mortality. Replacing saturated fat with PUFA, MUFA or high-quality carbohydrate will lower CHD events.

KEYWORDS:

Cohort studies; Heart attack; Heart death; Interventions; Meta-analyses; Polyunsaturated fat; Saturated fat; Systematic review

 

Successful Ageing in Nonagenarians: Bio-psychosocial Factors Determining Successful Ageing in Long-Lived Older Adults.

Chong MS, Tan CN, Yew S, Lim JP, Lim WS, Lieu PK.

J Am Med Dir Assoc. 2017 Nov 21. pii: S1525-8610(17)30589-3. doi: 10.1016/j.jamda.2017.10.015. [Epub ahead of print] No abstract available.

PMID: 29174561

In their seminal paper, Rowe and Kahn defined successful aging as having 3 main components: limited disease and disease-related disability, high cognitive and physical functional capacity, and active engagement with life. 1 Nonagenarians represent a unique and relevant catchment group to conduct research on successful aging. 2 Much of the prevailing literature focuses mainly on longevity per se rather than attributes that promote healthy aging and well-being in a group that has attained exceptional longevity. 3 Because biomedical constructs of successful aging that place an undue focus on absence of disease as criteria may not be the most relevant and applicable in the oldest-old, there is a need for an integrated multidimensional concept. 4 A recent article of successful aging among nonagenarians concluded that age-sensitive approaches would help us better understand factors that promote aging successfully among long-lived individuals. 2 Using a comprehensive biopsychosocial framework that incorporates biomedical, lifestyle, psychological, and social factors, we aim to determine the factors associated with successful aging among community-dwelling Chinese nonagenarians in Singapore.

 

Methods

 

We recruited 60 nonagenarians [30 successful agers (SA) and 30 with disability (NwD)] from January 2015 to December 2016 in the Successful Ageing in Nonagenarians Study (SANOS). This study was confined to subjects of Chinese ethnicity, who constitute the major ethnic group in Singapore. Community-dwelling nonagenarians were recruited from community services and outpatient clinics. Using a modified definition of Rowe and Kahn, we defined SA as independence in 5 activities of daily living (indoor movement, walking 400 m, stairs climbing, getting in and out of bed, and dressing) and Chinese Mini-Mental State Examination (CMMSE) score ≥21 (locally validated cut-off). 5 For NwD, we included nonagenarians who are dependent in at least 1 of the 5 activities of daily living and/or CMMSE <21. We excluded subjects with no caregiver, of non-Chinese ethnicity, and who are institutionalized. Ethical approval was obtained from the Domain-Specific Research Board of the National Healthcare Group. Consent was obtained from the study participants or their legally acceptable representative where appropriate.

 

We compared between SA and NwD groups in the following dimensions:

 

1. Biomedical factors, comprising a modified Barthel index of basic activities of daily living (ADL); Lawton instrumental ADL scale; CMMSE assessment of cognition; vascular risk factors of hypertension, hyperlipidemia, diabetes mellitus, atrial fibrillation, peripheral vascular disease, smoking history, ischemic heart disease, history of stroke or transient ischemic attack; and body mass index. Fasting blood samples for lipid profile and glucose were taken within 3 months of evaluation.

2. Lifestyle factors. We assessed engagement in activity >1 hour daily. We evaluated nutrition using the Mini Nutritional Assessment questionnaire, 24-hour food recall, and a locally validated semi-quantitative Food Frequency Questionnaire. 6 We also inquired about vegetarianism as this is a fairly common dietary practice among the Chinese elderly.

3. Psychological factors. We measured optimism using the revised Life Orientation Test which is a 6-item scale with higher scores indicating increased levels of optimism. 7 Resilience was measured using the 25-item Connor Davison Resilience Scale (CD-RISC). 8 We also studied personality factors of conscientiousness and neuroticism, 9 and assessed mood using the 15 item-Geriatric Depression Scale.

4. Social factors, comprising educational attainment, previous occupation, age of retirement, housing type, living arrangements, total household income, marital status, marital happiness, and religiosity. 9

Results

 

We studied 30 SA (mean age 93.3±2.2 years) and 30 NwD (mean age 94.0±3.3 years) subjects. Not surprisingly, the SA group had higher scores in CMMSE, basic ADL, and instrumental ADL (all P < .01). With the exception of stroke prevalence (0% vs 13.3%, P < .05), there was no difference in comorbidities. There was also no difference in body mass index, lipid profile or fasting glucose. For lifestyle factors, there was a significant difference in engagement of >1 hour of daily activity and overall nutritional status as measured via Mini Nutritional Assessment ( P < .05), although there was no difference in vegetarianism, or intake of vegetables, fruit, or fish. Food Frequency Questionnaire did not yield any group differences in energy, protein, fat, cholesterol, sodium, dietary fiber, calcium, iron, and vitamin C intake. For psychological factors, SA endorsed higher Life Orientation Test–Revised (17.1±2.6 vs 14.4±3.8, P = .0019) and Connor-Davidson Resilience Scale (76.4±8.6 vs 66.7±10.8, P = .0003) scores, indicating a more optimistic and resilient personality. SA were more conscientious (43.3±4.1 vs 39.3±5.5, P = .002), less neurotic (10.7±1.1 vs 14.3±5.1, P < .001), and had lower Geriatric Depression Scale scores (0.7±1.0 vs 1.8±2.4, P < .001). For social factors, there was a trend toward marital happiness in the SA group (39.1±8.6 vs 35.1±8.7, P = .09). Otherwise, both groups did not differ in demographic factors, socioeconomic factors, or religiosity ( Table 1 ).

 

Table 1

Demographic, Biomedical, Lifestyle, Psychological, and Social Factor Measurement

Total (n = 60) SA (n = 30) NwD (n = 30) P Value

Age, years 93.6±2.8 93.1±2.2 94.0±3.3 .190

Male, % 28.3 30.0 26.7 .774

Biomedical factors

Basic ADL 86.3±20.7 98.0±3.4 74.7±24.1 <.001

Instrumental ADL 6.0±2.6 7.7±0.7 4.3±2.7 <.001

CMMSE 20.2±4.9 23.7±2.4 16.8±4.3 <.001

Body mass index 21.1±3.6 21.8±3.2 20.4±3.8 .108

Hypertension, % 73.3 83.3 63.3 .080

Hyperlipidemia, % 53.3 63.3 43.3 .121

Diabetes mellitus, % 20.0 26.7 13.3 .197

Atrial fibrillation, % 5.0 3.3 6.7 .554

Ischemic heart disease, % 11.7 10.0 13.3 .688

Stroke/TIA, % 0.67 0.0 13.3 .038

Smoking, % 23.3 16.7 30.0 .461

Lifestyle factors

Mini Nutrition Assessment 25.0±3.2 26.3±2.0 23.8 ±3.7 .002

Vegetarian, % 1.7 0.0 3.3 .313

Daily fruit/vegetable intake, % 88.3 90.0 86.7 .688

Daily fish intake, % 33.3 23.3 43.3 .132

>1 hour activity daily, % 21.7 33.3 10.0 .007

Psychological factors

LOT-R 15.7±3.5 17.1±2.6 14.4±3.8 .002

CD-RISC 71.6±10.9 76.4±8.6 66.7±10.8 <.001

Conscientious Scale 41.3±5.2 43.3±4.1 39.3±5.5 .002

Neuroticism Scale 12.5±4.1 10.7±1.1 14.3±5.1 <.001

Geriatric Depression Scale 1.8±2.4 0.7±1.0 2.9±2.9 <.001

Social factors

Married, % 25.0 26.7 23.3 .655

Age of retirement, years 65.3±15.7 68.8±16.7 61.7±14.0 .118

Education, years 3.6±4.8 4.0±5.0 3.1±4.6 .457

Religiosity scale 16.3±6.4 17.6±6.1 14.9±6.6 .109

Marital Happiness Scale 37.1±8.8 39.1±8.6 35.1±8.7 .092 View full size

CD-RISC, Connor-Davison Resilience Scale; CMMSE, Chinese Mini-Mental State Examination; LOT-R, Life Orientation Test–Revised version; TIA, transient ischemic attack.

Values are mean±standard deviation unless otherwise indicated.

Discussion

Our study in a group of Chinese nonagenarians in Singapore who already has “success” in longevity allowed important insights into factors that promote aging successfully. Using the Katz approach of viewing successful aging from the perspective of multidimensional measurements, our study affirmed the utility of a multidimensional approach beyond the biomedical model. 3 Of note, the most striking difference between successful agers and nonagenarians with disability was in terms of psychological factors such as optimism, resilience, conscientiousness, low neuroticism, and fewer depressive symptoms; lifestyle factors such as low nutritional risk and engagement in activity; and social factors such as a good marital relationship. With the exception of stroke, disease factors appeared to be less salient in this long-lived group. Ironically, in our study, SA nonagenarians had a higher prevalence of hypertension, hyperlipidemia, and diabetes mellitus. Our results are consistent with the recommendations of the World Health and Aging Report of the World Health Organization, which emphasizes that “healthy aging is more than just the absence of disease” and highlights the importance of raising the intrinsic capacity throughout the life course. 10 Taken together, this highlights the importance of using age-sensitive multidimensional definitions of successful aging in the oldest-old that encompass psychosocial domains. 3 Our findings also suggest the potential of a life-course approach of culturally appropriate and evidence-based interventions that target lifestyle, environmental, and psychosocial dimensions to promote aging successfully that will support aging-in-place. 11 This is supported by recent work published showing interactions between familial longevity and environmental factors that affect health in old age in China. 12

In summary, using an enriched sample of successfully aged versus disabled nonagenarians, we demonstrated the salience of psychological, lifestyle, and social dimensions above and beyond the biomedical model. Because of the cross-sectional design, we cannot exclude reverse causality and, hence, the reported associations should preferably be replicated in longitudinal studies. To complement our findings that examines successful aging using the Rowe and Kahn paradigm, we also propose studies that examine successful aging using the complementary Havighurst approach of understanding successful aging from the perspectives of older persons themselves. 3

 

RS 10767664 gene variant in Brain Derived Neurotrophic Factor (BDNF) affect metabolic changes and insulin resistance after a standard hypocaloric diet.

de Luis DA, Fernández Ovalle H, Izaola O, Primo D, Aller R.

J Diabetes Complications. 2017 Oct 14. pii: S1056-8727(17)30417-8. doi: 10.1016/j.jdiacomp.2017.10.005. [Epub ahead of print]

PMID: 29174117

Abstract

BACKGROUND:

Role of BDNF variants on change in body weight and cardiovascular risk factors after weight loss remains unclear in obese patients.

OBJECTIVE:

Our aim was to analyze the effects of rs10767664 BDNF gene polymorphism on body weight, cardiovascular risk factors and serum adipokine levels after a standard hypocaloric diet in obese subjects.

DESIGN:

A Caucasian population of 80 obese patients was analyzed before and after 3months on a standard hypocaloric diet.

RESULTS:

Fifty patients (62.5%) had the genotype AA and 30 (37.5%) subjects had the next genotypes; AT (25 patients, 31.3%) or TT (5 study subjects, 6.3%) (second group). In non T allele carriers, the decreases in weight-3.4±2.9kg (T allele group -1.7±2.0kg:p=0.01), BMI -1.5±0.2kg (T allele group -1.2±0.5kg:p=0.02), fat mass-2.3±1.1kg (T allele group -1.7±0.9kg:p=0.009), waist circumference-3.8±2.4cm (T allele group -2.1±3.1cm:p=0.008), triglycerides -13.2±7.5mg/dl (T allele group +2.8±1.2mg/dl:p=0.02), insulin -2.1±1.9mUI/L (T allele group -0.3±1.0mUI/L:p=0.01), HOMA-IR -0.9±0.4 (T allele group -0.1±0.8:p=0.01) and leptin -10.1±9.5ng/dl (T allele group -3.1±0.2ng/dl:p=0.01) were higher than T allele carriers.

CONCLUSION:

rs10767664 variant of BDNF gene modify anthropometric and biochemical changes after weight loss with a hypocaloric diet.

KEYWORDS:

BDNF; Hypocaloric diet; Insulin; Insulin resistance; rs10767664

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[Dietary efficacy of a micronutrient combination in patients with recurrent upper respiratory tract infections. Results of a placebo-controlled doubleblind study.]

Schmidt K, Zirkler S.

MMW Fortschr Med. 2011 Oct;153(Suppl 3):83-89. doi: 10.1007/s15006-011-1630-2. German.

PMID: 29178046

Abstract

BACKGROUND AND OBJECTIVES:

An optimal vitamin and mineral supply may contribute to the enhancement of immune defenses and thus favorably influence the course and intensity of recurrent upper respiratory tract infections (URIs). In the present study the dietary efficacy and benefits of a micronutrient combination in patients with recurrent URIs was evaluated.

METHODS:

192 patients with recurrent URIs were enrolled in this randomized, placebo-controlled, double-blind multicenter trial for a study duration of 16 weeks. Efficacy variables were number, intensity and course of URIs (as assessed using a total common cold score [CCS]) and the alterations in micronutrient supply (vitamins C and D3, folic acid and selenium) during the study.

RESULTS:

In subjects who initially had at least two common cold symptoms (N = 107) the symptoms improved in the active group (AG) significantly more than in the placebo group (PG; ΔCCS: AG -6.9 ± 4.8; PG -5.4 ± 4.5; p = 0.034). In patients with initially severe common cold (CC) episodes the symptoms improved in the AG to a statistically significant extent (ΔCCS: AG -93.8%, PG -91.2%, p = 0.043). In the age group below 45 years significantly fewer AG than PG patients were absent from their job during the second or third CC episode (AG: 14.3%, PG: 47.8%, p = 0.038). Patients with vitamin-D deficiency and/or insufficient vitamin-C supply reported significantly fewer CC episodes in AG than in PG. In the course of the trial, in AG vs. PG the serum vitamin C, folic acid and selenium levels increased (p < 0.001). The concentration of 25(OH)D3 decreased in both groups, but less so in the AG (AG -8.8%; PG -14%; p = 0.001).

CONCLUSION:

Study results show the efficacy of a nutritional medical treatment with a special micronutrient combination in patients susceptible to infections and suffering from recurrent respiratory tract infections.

KEYWORDS:

Common cold disease; Immune system; Micro; Recurrent respiratory tract infections; Vitamin C; Vitamin D; nutrient combination

 

Body Mass Index and Vascular Disease in Men Aged 65 Years and Over: HIMS (Health In Men Study).

Lacey B, Yeap BB, Golledge J, Lewington S, McCaul KA, Norman PE, Flicker L, Almeida OP, Hankey GJ.

J Am Heart Assoc. 2017 Nov 27;6(12). pii: e007343. doi: 10.1161/JAHA.117.007343.

PMID: 29180456

http://jaha.ahajournals.org/content/6/12/e007343.long

Abstract

BACKGROUND:

Understanding the relationship between body mass index (BMI) and vascular disease at older age has become increasingly important in the many countries where both average age and BMI are rising.

METHODS AND RESULTS:

In this prospective cohort study, 12 203 men (aged ≥65) were recruited in 1996-1999 from the general population in Perth, Australia. To limit reverse causality, analyses excluded those with past vascular disease and the first 4 years of follow-up. During a further 8 (SD3) years of follow-up, there were 1136 first-ever major vascular events (nonfatal myocardial infarction, nonfatal stroke, or death from any vascular cause). Cox regression (adjusted for age, education, and smoking) related BMI at recruitment to incidence of major vascular events. At ages 65 to 94, the lowest risk of major vascular events was at ≈ 22.5 to 25 kg/m2. In the higher BMI range (≥25 kg/m2), 5 kg/m2 higher BMI was associated with 33% higher risk of major vascular events (hazard ratio, 1.33 [95% confidence interval, 1.18-1.49]): 24% higher risk of ischemic heart disease (1.24 [1.06-1.46]); 34% higher risk of stroke (1.34 [1.11-1.63]); and 78% higher risk of other vascular death (1.78 [1.32-2.41]). In the lower BMI range, there were fewer events and no strong evidence of an association (hazard ratio per 5 kg/m2 higher BMI, 0.82 [95% confidence interval, 0.61-1.12]).

CONCLUSIONS:

In this population of older men, risk of major vascular events was lowest at ≈ 22.5 to 25 kg/m2. Above this range, BMI was strongly related to incidence of major vascular events, with each 5 kg/m2 higher BMI associated with ≈30% higher risk.

KEYWORDS:

adiposity; body mass index; epidemiology; ischemic heart disease; stroke; vascular disease

 

Effects of Dark Chocolate and Almonds on Cardiovascular Risk Factors in Overweight and Obese Individuals: A Randomized Controlled‐Feeding Trial

Yujin Lee, Claire E. Berryman, Sheila G. West, C.‐Y. Oliver Chen, Jeffrey B. Blumberg, Karen G. Lapsley, Amy G. Preston, Jennifer A. Fleming, Penny M. Kris‐Etherton

Journal of the American Heart Association. 2017;6:e005162, originally published November 29, 2017

https://doi.org/10.1161/JAHA.116.005162

http://jaha.ahajournals.org/content/6/12/e005162

Abstract

Background Consumption of almonds or dark chocolate and cocoa has favorable effects on markers of coronary heart disease; however, the combined effects have not been evaluated in a well‐controlled feeding study. The aim of this study was to examine the individual and combined effects of consumption of dark chocolate and cocoa and almonds on markers of coronary heart disease risk.

Methods and Results A randomized controlled, 4‐period, crossover, feeding trial was conducted in overweight and obese individuals aged 30 to 70 years. Forty‐eight participants were randomized, and 31 participants completed the entire study. Each diet period was 4 weeks long, followed by a 2‐week compliance break. Participants consumed each of 4 isocaloric, weight maintenance diets: (1) no treatment foods (average American diet), (2) 42.5 g/d of almonds (almond diet [ALD]), (3) 18 g/d of cocoa powder and 43 g/d of dark chocolate (chocolate diet [CHOC]), or (4) all 3 foods (CHOC+ALD). Compared with the average American diet, total cholesterol, non–high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol after the ALD were lower by 4%, 5%, and 7%, respectively (P<0.05). The CHOC+ALD decreased apolipoprotein B by 5% compared with the average American diet. For low‐density lipoprotein subclasses, compared with the average American diet, the ALD showed a greater reduction in large buoyant low‐density lipoprotein particles (−5.7±2.3 versus −0.3±2.3 mg/dL; P=0.04), whereas the CHOC+ALD had a greater decrease in small dense low‐density lipoprotein particles (−12.0±2.8 versus −5.3±2.8 mg/dL; P=0.04). There were no significant differences between diets for measures of vascular health and oxidative stress.

Conclusions Our results demonstrate that consumption of almonds alone or combined with dark chocolate under controlled‐feeding conditions improves lipid profiles. Incorporating almonds, dark chocolate, and cocoa into a typical American diet without exceeding energy needs may reduce the risk of coronary heart disease.

Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01882881.

almondscardiovascular disease risk factorsdark chocolateflow‐mediated dilationlipids and lipoproteins

 

Visit‐to‐Visit Variability of Fasting Plasma Glucose and the Risk of Cardiovascular Disease and All‐Cause Mortality in the General Population

Anxin Wang, Xiaoxue Liu, Jie Xu, Xiaochen Han, Zhaoping Su, Shuohua Chen, Nan Zhang, Shouling Wu, Yongjun Wang, Yilong Wang

Journal of the American Heart Association. 2017;6:e006757, originally published November 29, 2017

https://doi.org/10.1161/JAHA.117.006757

http://jaha.ahajournals.org/content/6/12/e006757

Abstract

Background The association of short‐term variability of fasting plasma glucose (FPG) and mortality has been well investigated. However, the relationships between visit‐to‐visit variability of FPG over longer periods of follow‐up and cardiovascular disease (CVD) and all‐cause mortality are unclear. This study aimed to investigate these relationships.

Methods and Results The current analysis included 53 607 Chinese participants (mean age, 49.10 years) who were free of CVD in the Kailuan study. Participants were divided into 4 categories by quartiles of visit‐to‐visit variability of FPG. Visit‐to‐visit variability of FPG was defined as the coefficient of variation of 3 values of FPG that were measured from the examination periods of 2006 to 2007, 2008 to 2009, and 2010 to 2011. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for CVD and all‐cause mortality. After a mean follow‐up of 4.93 years, 4261 individuals developed CVD and 1545 individuals died. The incidence of CVD and all‐cause mortality was 5.04 and 5.85 per 1000 person‐years, respectively. After adjusting for mean FPG and other potential confounders, individuals in the highest quartile of variability of FPG compared with participants in the lowest quartile showed a 26% greater risk of developing CVD (hazard ratio, 1.26; 95% confidence interval, 1.08–1.47) and a 46% greater risk for all‐cause mortality (hazard ratio, 1.46; 95% confidence interval, 1.25–1.70).

Conclusions Independent of mean FPG and other baseline parameters, elevated visit‐to‐visit variability of FPG significantly increases the risk of CVD and all‐cause mortality in the general population. Measuring long‐term visit‐to‐visit variability of FPG is helpful for predicting the risk for CVD and all‐cause mortality.

all‐cause mortalitycardiovascular eventsdeathglucosevariabilityvisit‐to‐visit

 

Association of Thyroid Function With Life Expectancy With and Without Cardiovascular Disease: The Rotterdam Study.

Bano A, Dhana K, Chaker L, Kavousi M, Ikram MA, Mattace-Raso FUS, Peeters RP, Franco OH.

JAMA Intern Med. 2017 Nov 1;177(11):1650-1657. doi: 10.1001/jamainternmed.2017.4836.

PMID: 28975207

Abstract

IMPORTANCE:

Variations in thyroid function within reference ranges are associated with an increased risk of cardiovascular disease (CVD) and mortality. However, the impact of thyroid function on life expectancy (LE) and the number of years lived with and without CVD remains unknown.

OBJECTIVE:

To investigate the association of thyroid function with total LE and LE with and without CVD among euthyroid individuals.

DESIGN, SETTING, AND PARTICIPANTS:

The Rotterdam Study, a population-based, prospective cohort study. We included participants without known thyroid disease and with thyrotropin and free thyroxine (FT4) levels within the reference ranges.

MAIN OUTCOMES AND MEASURES:

Multistate life tables were used to calculate total LE and LE with and without CVD among thyrotropin and FT4 tertiles. Life expectancy estimates in men and women aged 50 years and older were obtained using prevalence, incidence rates, and hazard ratios for 3 transitions (healthy to CVD, healthy to death, and CVD to death), adjusting for sociodemographic and cardiovascular risk factors.

RESULTS:

The mean (SD) age of the 7785 participants was 64.7 (9.8) years, and 52.5% were women. Over a median follow-up of 8.1 (interquartile range, 2.7-9.9) years, we observed 789 incident CVD events and 1357 deaths. Compared with those in the lowest tertile, men and women in the highest thyrotropin tertile lived 2.0 (95% CI, 1.0 to 2.8) and 1.4 (95% CI, 0.2 to 2.4) years longer, respectively, of which, 1.5 (95% CI, 0.2 to 2.6) and 0.9 (95% CI, -0.2 to 2.0) years longer without CVD. Compared with those in the lowest tertile, the difference in life expectancy for men and women in the highest FT4 tertile was -3.2 (95% CI, -5.0 to -1.4) and -3.5 (95% CI, -5.6 to -1.5) years, respectively, of which, -3.1 (95% CI, -4.9 to -1.4) and -2.5 (95% CI, -4.4 to -0.7) years without CVD.

CONCLUSIONS AND RELEVANCE:

At the age of 50 years, participants with low-normal thyroid function live up to 3.5 years longer overall and up to 3.1 years longer without CVD than participants with high-normal thyroid function. These findings provide supporting evidence for a reevaluation of the current reference ranges of thyroid function and can help inform preventive and clinical care.

 

[The below paper is pdf-availed and the first page of two pages preview that is free to view shows apparently important relevant data.]

Trends and Disparities in the Number of Self-reported Healthy Older Adults in the United States, 2000 to 2014.

Davis MA, Guo C, Sol K, Langa KM, Nallamothu BK.

JAMA Intern Med. 2017 Nov 1;177(11):1683-1684. doi: 10.1001/jamainternmed.2017.4357. No abstract available.

PMID: 28975206

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2653447

 

[below papers are pdf-availed and the first two can be viewed from the journal's reference.]

Sample Size Matters When Drawing Conclusions on Alternate-Day Fasting Diet.

Portillo-Sanchez P, Gonzalez-Velazquez C, Mancillas-Adame L.

JAMA Intern Med. 2017 Nov 1;177(11):1700-1701. doi: 10.1001/jamainternmed.2017.5850. No abstract available.

PMID: 29114794

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2660140

>>>>>>>>>

Sample Size Matters When Drawing Conclusions on Alternate-Day Fasting Diet-Reply.

Trepanowski JF, Ravussin E, Varady KA.

JAMA Intern Med. 2017 Nov 1;177(11):1701. doi: 10.1001/jamainternmed.2017.5866. No abstract available.

PMID: 29114802

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2660133

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Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial.

Trepanowski JF, Kroeger CM, Barnosky A, Klempel MC, Bhutani S, Hoddy KK, Gabel K, Freels S, Rigdon J, Rood J, Ravussin E, Varady KA.

JAMA Intern Med. 2017 Jul 1;177(7):930-938. doi: 10.1001/jamainternmed.2017.0936.

PMID: 28459931

Abstract

IMPORTANCE:

Alternate-day fasting has become increasingly popular, yet, to date, no long-term randomized clinical trials have evaluated its efficacy.

OBJECTIVE:

To compare the effects of alternate-day fasting vs daily calorie restriction on weight loss, weight maintenance, and risk indicators for cardiovascular disease.

DESIGN, SETTING, AND PARTICIPANTS:

A single-center randomized clinical trial of obese adults (18 to 64 years of age; mean body mass index, 34) was conducted between October 1, 2011, and January 15, 2015, at an academic institution in Chicago, Illinois.

INTERVENTIONS:

Participants were randomized to 1 of 3 groups for 1 year: alternate-day fasting (25% of energy needs on fast days; 125% of energy needs on alternating "feast days"), calorie restriction (75% of energy needs every day), or a no-intervention control. The trial involved a 6-month weight-loss phase followed by a 6-month weight-maintenance phase.

MAIN OUTCOMES AND MEASURES:

The primary outcome was change in body weight. Secondary outcomes were adherence to the dietary intervention and risk indicators for cardiovascular disease.

RESULTS:

Among the 100 participants (86 women and 14 men; mean [sD] age, 44 [11] years), the dropout rate was highest in the alternate-day fasting group (13 of 34 [38%]), vs the daily calorie restriction group (10 of 35 [29%]) and control group (8 of 31 [26%]). Mean weight loss was similar for participants in the alternate-day fasting group and those in the daily calorie restriction group at month 6 (-6.8% [95% CI, -9.1% to -4.5%] vs -6.8% [95% CI, -9.1% to -4.6%]) and month 12 (-6.0% [95% CI, -8.5% to -3.6%] vs -5.3% [95% CI, -7.6% to -3.0%]) relative to those in the control group. Participants in the alternate-day fasting group ate more than prescribed on fast days, and less than prescribed on feast days, while those in the daily calorie restriction group generally met their prescribed energy goals. There were no significant differences between the intervention groups in blood pressure, heart rate, triglycerides, fasting glucose, fasting insulin, insulin resistance, C-reactive protein, or homocysteine concentrations at month 6 or 12. Mean high-density lipoprotein cholesterol levels at month 6 significantly increased among the participants in the alternate-day fasting group (6.2 mg/dL [95% CI, 0.1-12.4 mg/dL]), but not at month 12 (1.0 mg/dL [95% CI, -5.9 to 7.8 mg/dL]), relative to those in the daily calorie restriction group. Mean low-density lipoprotein cholesterol levels were significantly elevated by month 12 among the participants in the alternate-day fasting group (11.5 mg/dL [95% CI, 1.9-21.1 mg/dL]) compared with those in the daily calorie restriction group.

CONCLUSIONS AND RELEVANCE:

Alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or cardioprotection vs daily calorie restriction.

 

Association of circulating branched-chain amino acids with cardiometabolic traits differs between adults and the oldest-old.

Sun L, Hu C, Yang R, Lv Y, Yuan H, Liang Q, He B, Pang G, Jiang M, Dong J, Yang Z.

Oncotarget. 2017 Oct 4;8(51):88882-88893. doi: 10.18632/oncotarget.21489. eCollection 2017 Oct 24.

PMID: 29179484

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=21489&path%5B%5D=68286

Abstract

Branched-chain amino acids (BCAAs) are promising for their potential anti-aging effects. However, findings in adults suggest that circulating BCAAs are associated with cardiometabolic risk. Moreover, little information is available about how BCAAs influence clustered cardiometabolic traits in the oldest-old (>85 years), which are the fastest-growing segment of the population in developed countries. Here, we applied a targeted metabolomics approach to measure serum BCAAs in Chinese participants (aged 21-110 years) based on a longevity cohort. The differences of quantitative and dichotomous cardiometabolic traits were compared across BCAAs tertiles. A generalized additive model (GAM) was used to explore the dose-response relationship between BCAAs and the risk of metabolic syndrome (MetS). Overall, BCAAs were correlated with most of the examined cardiometabolic traits. The odds ratios for MetS across the increasing BCAA tertiles were 3.22 (1.70 - 6.12) and 5.27 (2.88 - 9.94, referenced to tertile 1) after adjusting for age and gender (Ptrend < 0.001). The association still existed after further controlling for lifestyle factors and inflammation factors. However, the correlations between circulating BCAAs and quantitative traits were weakened in the oldest-old, except for lipids, the levels of which were distinctly different from those in adults. The stratified analysis also suggested that the risky BCAAs-MetS association was more pronounced in adults than in the oldest-old. Moreover, generalized additive model (GAM)-based curve-fitting suggested that only when BCAAs exceeded a threshold (approximately 450 μmol/L) was the BCAAs-MetS association significant. The relationship might be aging-dependent and was more pronounced in adults than in the oldest-old.

KEYWORDS:

BCAAs; age-dependent; cardiometabolic trait; risk factor; the oldest-old

 

[Most of the below pdf-availed paper can be viewed from the journal's abstract page.]

Excessive Weight Gain, Obesity, and Cancer: Opportunities for Clinical Intervention.

Massetti GM, Dietz WH, Richardson LC.

JAMA. 2017 Nov 28;318(20):1975-1976. doi: 10.1001/jama.2017.15519. No abstract available.

PMID: 28973170

https://jamanetwork.com/journals/jama/article-abstract/2656710

This Viewpoint reviews evidence documenting an association between overweight and obesity and cancer and discusses the underacknowledged role of weight control counseling and community programs as a cancer prevention strategy.

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Heart failure in an ageing population.

The Lancet.

Lancet. 2017 Nov 22. pii: S0140-6736(17)33039-8. doi: 10.1016/S0140-6736(17)33039-8. [Epub ahead of print] No abstract available.

PMID: 29174127

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)33039-8/fulltext

Summary

An Article by Nathalie Conrad and colleagues published online on Nov 21 in The Lancet provides the most comprehensive epidemiology to date of the changing burden of heart failure in the UK according to age, sex, regional location, and socioeconomic status. Their data show an increase in the number of new heart failure diagnoses, at least partly because of an ageing population. Comorbidities also continued to increase for multiple chronic conditions such as hypertension, atrial fibrillation, diabetes, cancer, and osteoarthritis.

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Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals.

Conrad N, Judge A, Tran J, Mohseni H, Hedgecott D, Crespillo AP, Allison M, Hemingway H, Cleland JG, McMurray JJV, Rahimi K.

Lancet. 2017 Nov 21. pii: S0140-6736(17)32520-5. doi: 10.1016/S0140-6736(17)32520-5. [Epub ahead of print]

PMID: 29174292 Free Article

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32520-5/fulltext

http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(17)32520-5.pdf

Abstract

BACKGROUND:

Large-scale and contemporary population-based studies of heart failure incidence are needed to inform resource planning and research prioritisation but current evidence is scarce. We aimed to assess temporal trends in incidence and prevalence of heart failure in a large general population cohort from the UK, between 2002 and 2014.

METHODS:

For this population-based study, we used linked primary and secondary electronic health records of 4 million individuals from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex. Eligible patients were aged 16 years and older, had contributed data between Jan 1, 2002, and Dec 31, 2014, had an acceptable record according to CPRD quality control, were approved for CPRD and Hospital Episodes Statistics linkage, and were registered with their general practice for at least 12 months. For patients with incident heart failure, we extracted the most recent measurement of baseline characteristics (within 2 years of diagnosis) from electronic health records, as well as information about comorbidities, socioeconomic status, ethnicity, and region. We calculated standardised rates by applying direct age and sex standardisation to the 2013 European Standard Population, and we inferred crude rates by applying year-specific, age-specific, and sex-specific incidence to UK census mid-year population estimates. We assumed no heart failure for patients aged 15 years or younger and report total incidence and prevalence for all ages (>0 years).

FINDINGS:

From 2002 to 2014, heart failure incidence (standardised by age and sex) decreased, similarly for men and women, by 7% (from 358 to 332 per 100 000 person-years; adjusted incidence ratio 0·93, 95% CI 0·91-0·94). However, the estimated absolute number of individuals with newly diagnosed heart failure in the UK increased by 12% (from 170 727 in 2002 to 190 798 in 2014), largely due to an increase in population size and age. The estimated absolute number of prevalent heart failure cases in the UK increased even more, by 23% (from 750 127 to 920 616). Over the study period, patient age and multi-morbidity at first presentation of heart failure increased (mean age 76·5 years [sD 12·0] to 77·0 years [12·9], adjusted difference 0·79 years, 95% CI 0·37-1·20; mean number of comorbidities 3·4 [sD 1·9] vs 5·4 [2·5]; adjusted difference 2·0, 95% CI 1·9-2·1). Socioeconomically deprived individuals were more likely to develop heart failure than were affluent individuals (incidence rate ratio 1·61, 95% CI 1·58-1·64), and did so earlier in life than those from the most affluent group (adjusted difference -3·51 years, 95% CI -3·77 to -3·25). From 2002 to 2014, the socioeconomic gradient in age at first presentation with heart failure widened. Socioeconomically deprived individuals also had more comorbidities, despite their younger age.

INTERPRETATION:

Despite a moderate decline in standardised incidence of heart failure, the burden of heart failure in the UK is increasing, and is now similar to the four most common causes of cancer combined. The observed socioeconomic disparities in disease incidence and age at onset within the same nation point to a potentially preventable nature of heart failure that still needs to be tackled.

 

The price of blood is measured in iron.

Mast AE, Murphy EL.

Lancet. 2017 Sep 20. pii: S0140-6736(17)32156-6. doi: 10.1016/S0140-6736(17)32156-6. [Epub ahead of print] No abstract available.

PMID: 28941949 Free Article

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32156-6/fulltext

>>>>>>>>>>>>>>>>>>

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors.

Di Angelantonio E, Thompson SG, Kaptoge S, Moore C, Walker M, Armitage J, Ouwehand WH, Roberts DJ, Danesh J; INTERVAL Trial Group.

Lancet. 2017 Sep 20. pii: S0140-6736(17)31928-1. doi: 10.1016/S0140-6736(17)31928-1. [Epub ahead of print]

PMID: 28941948 Free Article

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31928-1/fulltext

Abstract

BACKGROUND:

Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries.

METHODS:

In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants.

FINDINGS:

45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59-1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69-0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76-0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39-0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups.

INTERPRETATION:

Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency.

 

[The below papers are pdf-availed.]

Salt-responsive gut commensal modulates TH17 axis and disease

Nicola Wilck, Mariana G. Matus, Sean M. Kearney, Scott W. Olesen, Kristoffer Forslund+ et al.

High salt intake changed the gut microbiome and increased TH17 cell numbers in mice, and reduced intestinal survival of Lactobacillus species, increased the number of TH17 cells and increased blood pressure in humans.

Abstract

A Western lifestyle with high salt consumption can lead to hypertension and cardiovascular disease. High salt may additionally drive autoimmunity by inducing T helper 17 (TH17) cells, which can also contribute to hypertension. Induction of TH17 cells depends on gut microbiota; however, the effect of salt on the gut microbiome is unknown. Here we show that high salt intake affects the gut microbiome in mice, particularly by depleting Lactobacillus murinus. Consequently, treatment of mice with L. murinus prevented salt-induced aggravation of actively induced experimental autoimmune encephalomyelitis and salt-sensitive hypertension by modulating TH17 cells. In line with these findings, a moderate high-salt challenge in a pilot study in humans reduced intestinal survival of Lactobacillus spp., increased TH17 cells and increased blood pressure. Our results connect high salt intake to the gut-immune axis and highlight the gut microbiome as a potential therapeutic target to counteract salt-sensitive conditions.

See also:

Microbiota: A high-pressure situation for bacteria.

Relman DA.

Nature. 2017 Nov 15. doi: 10.1038/nature24760. [Epub ahead of print] No abstract available.

PMID: 29143820

Analyses in mice suggest that dietary salt increases blood pressure partly by affecting some of the microbes that inhabit the gut. The implications of this work for hypertension warrant further study in humans. See Article p.585

High blood pressure is a leading cause of cardiovascular disease and hence preventable death in the United States1, and is an increasingly prevalent and costly global health burden. Blood-pressure control in humans is inadequately understood — debate swirls around the contribution of dietary salt in particular. On page 585, Wilck et al.2 draw connections between dietary salt, microorganisms in the gut, immune responses and blood pressure.

Processed foods and Western diets are packed with salt. Average daily sodium intake in the United States is more than 3.4 grams (equivalent to 8.5 g of table salt)3, despite the fact that guidelines4 recommend an intake of less than 2.3 g (5.8 g of salt). Most studies show that excess sodium consumption raises blood pressure in a dose-dependent manner4. But blood-pressure responses to salt are variable and are generally detected in fewer than half of all subjects5. Known sources of such variability include genetics, dietary intake of other nutrients such as potassium, and kidney disease. In addition, responses to sodium intake are more pronounced if individuals have high blood pressure (hypertension)5.

Previous work6 has suggested that high salt intake increases the number and activity of immune cells called T lymphocytes, especially a pro-inflammatory subset called TH17 cells. Activated TH17 cells produce the immune-cell signalling factor interleukin-17, which not only promotes hypertension and inflammation in artery walls6,7, but also induces autoimmune diseases8.

Wilck et al. sought to determine whether gut microbes (collectively known as the gut microbiota) have a role in mediating the effects of a high-salt diet (HSD). The authors fed mice an HSD for three weeks and analysed the composition of the animals' gut microbiota by sequencing DNA from faecal samples. There were no major changes in composition; however, a machine-learning algorithm identified a DNA sequence that became less abundant in mice during HSD and more abundant when mice were returned to a normal diet. The sequence matched that of the bacterium Lactobacillus murinus.

The researchers recovered L. murinus from mouse faeces, and demonstrated in vitro that its growth was inhibited by salt concentrations equivalent to those found in the colons of mice fed an HSD. This bacterial species is not seen in humans, but the researchers found similar salt-sensitive growth in some human-associated Lactobacillus species. As expected, HSD caused hypertension in mice, but oral administration of L. murinus blunted this effect.

Wilck and colleagues found that L. murinus administration also prevented HSD-induced exacerbation of an autoimmune disease that can be experimentally generated in mice — actively induced experimental autoimmune encephalomyelitis (EAE). Administration of L. murinus was associated with a reduction in the numbers of TH17 cells, which mediate EAE, in the intestinal wall, spleen and spinal cord (Fig. 1).

Figure 1: A possible role for gut microbes in regulating blood pressure in mice.

Figure 1 a, Bacteria of the genus Lactobacillus, such as L. murinus, convert the dietary amino acid tryptophan into compounds called indoles in the lumen region of the gut. Wilck et al.2 have demonstrated in mice that one of these indoles prevents differentiation of immune cells called T lymphocytes into TH17 cells in the gut mucosa. b, The authors showed that feeding mice a high-salt diet causes a decrease in the levels of L. murinus in the gut. This diet and decrease in L. murinus was associated with an increase in the number and activation of TH17 cells. These cells produce a pro-inflammatory molecule called interleukin-17 (IL-17), which is thought to promote high blood pressure (hypertension) and accompanying inflammation in artery walls, and exacerbate an autoimmune disease in mice dubbed actively induced experimental autoimmune encephalomyelitis (EAE).

What links decreases in L. murinus to increased numbers of TH17 cells? Lactobacillus species produce compounds called indoles from the dietary amino acid tryptophan, and treatment with indoles reduces the severity of actively induced EAE in mice9. The authors demonstrated that levels of indoles decreased when mice were fed an HSD, but were restored by administration of L. murinus. They then showed that one indole metabolite downregulated differentiation of T lymphocytes into TH17 cells.

Do these observations translate to humans? Wilck et al. gave 12 healthy people 6 g of supplemental sodium chloride per day for 14 days. The subjects' mean blood pressure increased over time, as did the numbers of TH17 cells in their blood. In four of the five individuals who had Lactobacillus species in their guts before treatment, five species became undetectable after two weeks. Ten of the people gained extra Lactobacillus species during treatment, but overall Lactobacillus abundance declined. The authors drew control data from previous studies.

Wilck and colleagues' animal analysis, like many such studies, has provided key insights and raised compelling questions about the role of the microbiota in regulating host traits. However, there are several caveats when considering whether these findings will translate to humans. First, the authors gave mice 0.3 g of salt daily, which is a 15-fold increase from their normal intake. This high-salt environment would be difficult to create in humans because the equivalent daily dose for a 70-kg human, scaled by surface area, would be roughly 170 g — much more than humans could tolerate. Furthermore, most dietary sodium in humans is typically absorbed in the small intestine10. Thus, if elevated salt intake has direct effects on the gut microbiota, these effects probably occur before nutrients reach the colon, which was studied here.

Second, Wilck and colleagues' human data concern a specific scenario — people with normal blood pressure on an HSD for a relatively short time. This scenario and these findings are not necessarily informative about people who have chronic hypertension, particularly those with other underlying health problems, because of additional confounding factors.

Finally, the authors did not analyse whether changes in the abundance of Lactobacillus species correlated with the magnitude of changes in blood pressure, which could have helped to show a causal relationship between these factors. A larger study that includes people with normal and high blood pressure, compares various salt doses and a placebo, and takes functional readouts of the microbiota over time is eagerly awaited.

The list of complex diseases in which the gut microbiota might play a part is growing, but careful attention to interacting co-factors is needed when testing hypotheses. For instance, when considering a proposed role11 for the microbiota in cardiovascular disease, several variables must be taken into account. Gut microbes produce the molecule trimethylamine from dietary compounds found in red meat, and the liver converts it to trimethylamine oxide (TMAO). In animals, increases in TMAO promote a condition called atherosclerosis11, which increases the risk of heart attack and stroke. However, TMAO production is not necessary for the development of atherosclerosis, and other factors are required in addition to gut microbes for TMAO production. Thus, the gut microbiota contributes to atherosclerosis, but only in individuals who have certain combinations of microbes, diet and other risk factors.

Should hypertension be added to the list of conditions promoted by the gut microbiota? Future studies will no doubt tell. If this connection is real, one might predict — because of other variable factors — that the effects will be modest and restricted to a subset of individuals. Nonetheless, even modest effects are more than worthy of further study, because of the profound potential for global health benefits.

 

[The below Neuron paper is pdf-availed.]

Editors' Choice

Science 24 Nov 2017:

Vol. 358, Issue 6366, pp. 1016

NEUROSCIENCE

Rescuing remyelination

Lisa D. Chong

Targeting the blood-clotting protein fibrinogen could help promote brain repair after injury. In many brain injuries and neurodegenerative diseases, such as multiple sclerosis, neurons lose their myelin coating, reducing their ability to transmit signals. Petersen et al. have discovered that when the blood-brain barrier is disrupted, fibrinogen from the blood leaks into the central nervous system and blocks myelination by activating the bone morphogenetic protein (BMP) signaling pathway in oligodendrocyte progenitor cells. These precursors then fail to differentiate into mature oligodendrocytes needed for myelin repair. Inhibiting a BMP receptor in cultured oligodendrocyte progenitor cells and depleting fibrinogen in an animal model of demyelination enhanced remyelination, raising the possibility of new therapies for brain damage.

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Neuron 96, 1 (2017).

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Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage.

Petersen MA, Ryu JK, Chang KJ, Etxeberria A, Bardehle S, Mendiola AS, Kamau-Devers W, Fancy SPJ, Thor A, Bushong EA, Baeza-Raja B, Syme CA, Wu MD, Rios Coronado PE, Meyer-Franke A, Yahn S, Pous L, Lee JK, Schachtrup C, Lassmann H, Huang EJ, Han MH, Absinta M, Reich DS, Ellisman MH, Rowitch DH, Chan JR, Akassoglou K.

Neuron. 2017 Oct 19. pii: S0896-6273(17)30976-5. doi: 10.1016/j.neuron.2017.10.008. [Epub ahead of print]

PMID: 29103804

Abstract

Blood-brain barrier (BBB) disruption alters the composition of the brain microenvironment by allowing blood proteins into the CNS. However, whether blood-derived molecules serve as extrinsic inhibitors of remyelination is unknown. Here we show that the coagulation factor fibrinogen activates the bone morphogenetic protein (BMP) signaling pathway in oligodendrocyte progenitor cells (OPCs) and suppresses remyelination. Fibrinogen induces phosphorylation of Smad 1/5/8 and inhibits OPC differentiation into myelinating oligodendrocytes (OLs) while promoting an astrocytic fate in vitro. Fibrinogen effects are rescued by BMP type I receptor inhibition using dorsomorphin homolog 1 (DMH1) or CRISPR/Cas9 activin A receptor type I (ACVR1) knockout in OPCs. Fibrinogen and the BMP target Id2 are increased in demyelinated multiple sclerosis (MS) lesions. Therapeutic depletion of fibrinogen decreases BMP signaling and enhances remyelination in vivo. Targeting fibrinogen may be an upstream therapeutic strategy to promote the regenerative potential of CNS progenitors in diseases with remyelination failure.

KEYWORDS:

NG2 cells; ancrod; cell fate; fibrin; myelin; neonatal brain injury; neuroinflammation; regeneration; stem/progenitor cells; vasculature

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Transfusion of Red Blood Cells Stored More Than 28 Days Is Associated with Increased Morbidity Following Spine Surgery.

Purvis TE, Goodwin CR, Molina CA, Frank SM, Sciubba DM.

Spine (Phila Pa 1976). 2017 Nov 17. doi: 10.1097/BRS.0000000000002464. [Epub ahead of print]

PMID: 29189567

Abstract

STUDY DESIGN:

Retrospective study.

OBJECTIVE:

To describe the association between storage duration of packed red blood cells (PRBCs) and perioperative adverse events in patients undergoing spine surgery at a tertiary care center.

SUMMARY OF BACKGROUND DATA:

Despite retrospective studies that have shown that longer PRBC storage duration worsens patient outcomes, randomized clinical trials have found no difference in outcomes. However, no studies have examined the impact of giving the oldest blood (28 days-old or more) on morbidity within spine surgery.

METHODS:

The surgical administrative database at our institution was queried for patients transfused with PRBCs who underwent spine surgery between December 4, 2008 and June 26, 2015. Patients undergoing spinal fusion, tumor-related surgeries, and other identified spine surgeries were included. Patients were divided into two groups based on storage duration of blood transfused: exclusively ≤ 28 days' storage or exclusively >28 days' storage. The primary outcome was composite in-hospital morbidity, which included: (1) infection, (2) thrombotic event, (3) renal injury, (4) respiratory event, and/or (5) ischemic event.

RESULTS:

In total, 1,141 patients who received a transfusion were included for analysis in this retrospective study; 710 were transfused exclusively with PRBCs ≤ 28 days' storage and 431 exclusively with PRBCs >28 days' storage. Perioperative complications occurred in 119 patients (10.4%). Patients who received blood stored for >28 days had higher odds of developing any one complication (odds ratio [OR] = 1.82; 95% confidence interval [CI], 1.20-2.74; P = 0.005) even after adjusting for competing perioperative risk factors.

CONCLUSIONS:

Blood stored for >28 days is independently associated with higher odds of developing perioperative complications in patients transfused during spinal surgery. Our results suggest that blood storage duration may be an appropriate parameter to consider when developing institutional transfusion guidelines that seek to optimize patient outcomes.

LEVEL OF EVIDENCE: 3.

 

Socio-economic factors associated with an increase in fruit and vegetable consumption: a 12-year study in women from the E3N-EPIC study.

Affret A, Severi G, Dow C, Mancini FR, Rey G, Delpierre C, Clavel-Chapelon F, Boutron-Ruault MC, Fagherazzi G.

Public Health Nutr. 2017 Nov 29:1-16. doi: 10.1017/S1368980017003196. [Epub ahead of print]

PMID: 29183405

Abstract

OBJECTIVE:

To identify individual and contextual socio-economic factors associated with an increase in fruit and vegetable (F&V) consumption over a 12-year period and evaluate if some socio-economic factors were differentially associated with the change in consumption of some types of F&V.

DESIGN:

Associations between increased F&V consumption and socio-economic factors were studied with multivariate logistic regression.

SETTING:

E3N, a French prospective cohort study of 98 995 women.

SUBJECTS:

E3N participants (n 58 193) with information on diet in 1993 and 2005, and numerous individual and contextual socio-economic factors available.

RESULTS:

Associations between some individual socio-economic factors and changes in F&V consumption were observed. For instance, women who lived in a large household (>3 children v. no child) had higher probability of increasing their vegetable consumption (OR=1·33; 95 % CI 1·24, 1·42). This association was driven by higher consumption of courgette and raw cucumber. Living with a partner was associated with higher odds of increasing consumption of fruits (OR=1·07; 95 % CI 1·02, 1·13) such as pear, peach and grape.

CONCLUSIONS:

Certain individual socio-economic factors, but none of the contextual socio-economic factors examined, were associated with an increase in F&V consumption. Factors associated with an increase in total F&V consumption were not necessarily associated with an increase in fruit or vegetable consumption separately, or with an increase in each subtype of fruit or vegetable. Magnitudes of the different associations observed also differed when F&V were considered together, separately or by subtype. Increases in F&V consumption were mostly observed in women with high socio-economic position. To develop effective nutritional interventions and policies that take the socio-economic environment of individuals into account, we recommend future research to further focus on (i) pathways through which population characteristics might influence changes in F&V consumption and (ii) existing interactions between individual and contextual socio-economic factors.

KEYWORDS:

E3N-EPIC cohort; Epidemiology; Evolution of diet; Fruit and vegetable; Socio-economic environment

 

Short-Term Impact of a Combined Nutraceutical on Cognitive Function, Perceived Stress and Depression in Young Elderly with Cognitive Impairment: A Pilot, Double-Blind, Randomized Clinical Trial.

Cicero AF, Bove M, Colletti A, Rizzo M, Fogacci F, Giovannini M, Borghi C.

J Prev Alzheimers Dis. 2017;4(1):12-15. doi: 10.14283/jpad.2016.10.

PMID: 29188854

Abstract

BACKGROUND:

The prevalence of senile dementia is increasing worldwide, especially in the developed countries. Nevertheless, drug therapy isn't often enough to treat this condition. Researchers are evaluating the possible impact of a preventive approach, based on an improvement of lifestyle and the intake of micronutrients. Moreover, there is an increasing interest for combined nutraceuticals that can act as memory and learning enhancers, with a significant and beneficial potential on the cognitive disorders.

OBJECTIVE:

To evaluate the effects of a rational assemblage of nutraceuticals on cognitive functions in a sample of 30 elderly subjects.

DESIGN:

Double bind, cross-over designed trial versus placebo Setting: outpatient clinical practice.

PARTICIPANTS:

30 elderly subjects with basal Mini-Mental State Examination score between 20 and 27 and self-perceived cognitive decline.

INTERVENTION:

Treatment with a combination of nutraceuticals based on Bacopa monnieri, L-theanine, Crocus sativus, copper, folate and vitamins of B and D group. After2 months of treatment or placebo.

MEASUREMENTS:

Patients were evaluated with Mini-Mental State Examination (MMSE), Perceived Stress Questionnaire (PSQ) and Index and Self-Rating Depression Scale (SRDS).

RESULTS:

MMSE and PSQ Index significantly improved in the active treatment arm, both versus baseline and versus the parallel arm. Both groups experienced a significant improving in the SRDS scores.

CONCLUSIONS:

We obtained a good and significant improvement of the cognitive functions tested with the MMSE, PSQ-Index and SRDS score, after 2 months of combined therapy of nutraceuticals. Further confirmation will be needed to verify these observations on the middle and long term in a larger number of subjects.

KEYWORDS:

Clinical trial ; cognitive impairment; depression; dietary supplement; elderly

 

Changes in Lean Mass and Serum Myostatin with Habitual Protein Intake and High-Velocity Resistance Training.

Binns A, Gray M, Henson AC, Fort IL.

J Nutr Health Aging. 2017;21(10):1111-1117. doi: 10.1007/s12603-017-0883-6.

PMID: 29188869

Abstract

OBJECTIVES:

Examine the associations between dietary protein intake, lean mass (LM), and serum myostatin (Mstn) levels among community-dwelling older adults participating in a 20-week high-velocity resistance training (HVRT) program.

DESIGN, SETTING, AND PARTICIPANTS:

This longitudinal study consisted of 33 community-dwelling, older adults (mean age 77.0 years, SD = 6.4); all of which obtained physician clearance prior to study participation.

MEASUREMENTS:

Twenty-five females and eight males were randomized to a control (CON) or HVRT group. Anthropometric measures were obtained via dual energy x-ray absorptiometry (DXA) and peripheral venous blood draw used for serum myostatin analysis. Exercise was performed twice per week for 20 consecutive weeks. Food intake estimation with a diet history questionnaire (DHQ) was used for protein intake comparison to the recommended dietary allowance (RDA). All measures were recorded both prior to and following study participation.

RESULTS:

Altogether, protein was consumed in amounts more generous (1.01 ± 0.47 g·kg-1·d-1) than that of the RDA (0.8 g·kg-1·d-1). As a result of significant LM differences among men and women (p < 0.01), additional data were analyzed specific to sex. Serum myostatin was greater among females (6681.8 ± 3155.0 pg·mL-1) than males (5560.0 ± 2946.1 pg·mL-1); however, these values were not significantly different (p = 0.39). Combined, protein consumption and serum myostatin did not significantly influence LM among males (p = 0.09) or females (p = 0.71). Irrespective of training group, significant changes were not exhibited in dietary intake patterns, LM, or serum myostatin.

CONCLUSIONS:

Contrary to the proposed hypothesis, results suggest protein consumption and circulating serum myostatin levels did not significantly influence LM among older adults. Although HVRT positively impacts LM, neither exercise group displayed significant changes in LM. Therefore, further research is needed examining dietary intake, exercise modality, and myostatin downregulation as non-pharmacological approaches to combating sarcopenia.

KEYWORDS:

Older adults; myostatin; protein consumption

 

Intake of a Protein-Enriched Milk and Effects on Muscle Mass and Strength. A 12-Week Randomized Placebo Controlled Trial among Community-Dwelling Older Adults.

Ottestad I, Løvstad AT, Gjevestad GO, Hamarsland H, Šaltytė Benth J, Andersen LF, Bye A, Biong AS, Retterstøl K, Iversen PO, Raastad T, Ulven SM, Holven KB.

J Nutr Health Aging. 2017;21(10):1160-1169. doi: 10.1007/s12603-016-0856-1.

PMID: 29188875

Abstract

OBJECTIVES:

To investigate the effect of 20 g protein with breakfast and evening meal on muscle mass, muscle strength and functional performance in older adults.

DESIGN:

A double-blinded randomized controlled study.

SETTING:

Oslo and Akershus University College of Applied Sciences, Norway.

PARTICIPANTS:

Healthy community-dwelling men and women (≥ 70 years) with reduced physical strength and/or performance.

INTERVENTION:

Subjects were randomly assigned to receive either protein-enriched milk (2 x 0.4 L/d; protein group) or an isocaloric carbohydrate drink (2 x 0.4 L/d; control group) with breakfast and evening meal for 12 weeks.

MEASUREMENTS:

The primary endpoints were muscle mass measured by dual X-ray absorptiometry, and tests of muscle strength (one repetition maximum test of chest press and leg press) and functional performance (handgrip strength, stair calimb and repeated chair rise).

RESULTS:

In total, 438 subjects were screened, 50 subjects were randomized and 36 completed the study. Chest press improved significantly in the protein (1.3 kg (0.1-2.5), p=0.03) and the control group (1.5 kg (0.0-3.0), p=0.048), but with no difference between the groups (p=0.85). No significant change in leg press (p=0.93) or muscle mass (p=0.54) were observed between the protein and the control group. Nor did we observe any significant differences in the functional performance tests (p>0.05 for all tests) between the groups.

CONCLUSION:

Increased protein intake (2 x 20 g/d) did not significantly improve muscle mass, muscle strength or functional performance in healthy older weight stable adults. Whether intake of > 20 g protein to each meal is necessary for preservation of muscle mass and strength in older adults should be further investigated in a larger study. This underscores the need for well-designed studies that can differentiate between the effect of protein intake and increased energy. This trial was registered at Clinicaltrials.gov (ID no. NCT02218333).

KEYWORDS:

Protein; milk; muscle mass; muscle strength; older adults

 

Intake of Fruit and Vegetables and the Incident Risk of Cognitive Disorders: A Systematic Review and Meta-Analysis of Cohort Studies.

Wu L, Sun D, Tan Y.

J Nutr Health Aging. 2017;21(10):1284-1290. doi: 10.1007/s12603-017-0875-6.

PMID: 29188891

Abstract

OBJECTIVES:

No quantitative assessment has been performed to specifically link the consumption of fruit and vegetables with the incident risk of cognitive disorders.

METHODS:

We searched the PubMed and the Embase databases (both from the inception to June 13th, 2016) for records that report the intake of fruit and vegetables and the risk of developing cognitive disorders (Alzheimer's disease, dementia, and cognitive decline/impairment). A generic inverse-variance method (random-effects model) was used to combine the relative risks (RRs) and 95% confidence intervals (CIs). To explore the potential sources of heterogeneity, we performed the subgroup and meta-regression analyses by pre-specified characteristics.

RESULTS:

We identified 6 cohorts involving a total of 21,175 participants. The pooled analysis showed that consumption of fruit and vegetables was inversely associated with the incident risk of cognitive disorders, and the pooled RR (95% CI) was 0.74 (0.62, 0.88), with evidence of significant heterogeneity (I2 =68%). Furthermore, we found that the significant heterogeneity might be attributed to the ethnic difference.

CONCLUSION:

Further large prospective studies should be performed to quantify the potential dose-response patterns of fruit and/or vegetables intake and to explore the role of fruit or vegetables consumption separately on cognitive disorders in different populations.

KEYWORDS:

Alzheimer’s disease; Fruit and vegetables; cognitive disorders; dementia; meta-analysis

 

Intake of dietary fat and fat subtypes and risk of premenstrual syndrome in the Nurses' Health Study II.

Houghton SC, Manson JE, Whitcomb BW, Hankinson SE, Troy LM, Bigelow C, Bertone-Johnson ER.

Br J Nutr. 2017 Nov;118(10):849-857. doi: 10.1017/S0007114517002690.

PMID: 29189192

Abstract

Approximately 8-20 % of reproductive-aged women experience premenstrual syndrome (PMS), substantially impacting quality of life. Women with PMS are encouraged to reduce fat intake to alleviate symptoms; however, its role in PMS development is unclear. We evaluated the association between dietary fat intake and PMS development among a subset of the prospective Nurses' Health Study II cohort. We compared 1257 women reporting clinician-diagnosed PMS, confirmed by premenstrual symptom questionnaire and 2463 matched controls with no or minimal premenstrual symptoms. Intakes of total fat, subtypes and fatty acids were assessed via FFQ. After adjustment for age, BMI, smoking, Ca and other factors, intakes of total fat, MUFA, PUFA and trans-fat measured 2-4 years before were not associated with PMS. High SFA intake was associated with lower PMS risk (relative risk (RR) quintile 5 (median=28·1 g/d) v. quintile 1 (median=15·1 g/d)=0·75; 95 % CI 0·58, 0·98; P trend=0·07). This association was largely attributable to stearic acid intake, with women in the highest quintile (median=7·4 g/d) having a RR of 0·75 v. those with the lowest intake (median=3·7 g/d) (95 % CI 0·57, 0·97; P trend=0·03). Individual PUFA and MUFA, including n-3 fatty acids, were not associated with risk. Overall, fat intake was not associated with higher PMS risk. High intake of stearic acid may be associated with a lower risk of developing PMS. Additional prospective research is needed to confirm this finding.

KEYWORDS:

NHS2 Nurses’ Health Study II; PMS premenstrual syndrome; RR relative risk; Dietary fat; Epidemiology; Fatty acids; Premenstrual syndrome; Prospective studies

 

Acute effect of dietary nitrate on forearm muscle oxygenation, blood volume and strength in older adults: A randomized clinical trial.

de Oliveira GV, Morgado M, Conte-Junior CA, Alvares TS.

PLoS One. 2017 Nov 30;12(11):e0188893. doi: 10.1371/journal.pone.0188893. eCollection 2017.

PMID: 29190751

Abstract

Both recovery time of post-exercise muscle oxygenation and muscle strength decline with aging. Although beetroot consumption has been shown to improve muscle oxygenation and exercise performance in adults, these effects in the elderly has not been addressed. The aim of the present study was to evaluate the effect of a beetroot-based gel (BG) on muscle O2 saturation, blood volume (tHb) and handgrip strength in the elderly in response to handgrip exercise. In a randomized crossover double-blind design, twelve older subjects consumed BG (100 g of beetroot-based gel containing ~ 12 mmol nitrate) or PLA (100 g of nitrate-depleted gel nitrate-depleted). The subjects performed a rhythmic handgrip exercise which consisted of a one 1-min set at 30% of the maximal voluntary contraction (MVC) of each subject, followed by a 1 min recovery. The muscle oxygenation parameters and tHb were continuously monitored by using near-infrared spectroscopy. MVC was evaluated at baseline, immediately after exercise, and 30 min afterwards. The muscle O2 resaturation rate during exercise recovery was greater in the BG when compared to PLA condition (1.43 ± 0.77 vs 1.02 ± 0.48%.s-1; P < 0.05). Significant increase was observed in tHb during exercise recovery (10.25 ± 5.47 vs 6.72 ± 4.55 μM; P < 0.05) and significant reduction of handgrip strength decline was observed 30 min after exercise in BG (- 0.24 ± 0.18 vs-0.39 ± 0.20 N; P < 0.05). In summary, a single dose of a beetroot-based gel speeds up muscle O2 resaturation, increases blood volume and improves recovery of handgrip strength after handgrip exercise in older adults.

 

The Interplay of Personality and Functional Health in Old and Very Old Age: Dynamic Within-Person Interrelations Across up to 13 Years.

Mueller S, Wagner J, Smith J, Voelkle MC, Gerstorf D.

J Pers Soc Psychol. 2017 Nov 30. doi: 10.1037/pspp0000173. [Epub ahead of print]

PMID: 29189025

https://www.researchgate.net/profile/Swantje_Mueller/publication/319839642_The_Interplay_of_Personality_and_Functional_Health_in_Old_and_Very_Old_Age_Dynamic_Within-Person_Interrelations_Across_up_to_13_Years/links/59e2354c0f7e9b97fbe761eb/The-Interplay-of-Personality-and-Functional-Health-in-Old-and-Very-Old-Age-Dynamic-Within-Person-Interrelations-Across-up-to-13-Years.pdf

Abstract

Conceptual and empirical work has long suggested that personality and health are closely intertwined later in life. Little is known, however, about the nature and direction of time-ordered associations between the 2 domains within-persons. We applied continuous time auto- and cross-effects models to up to 6 waves of 13-year longitudinal data from the Berlin Aging Study (N = 516, M = 84.92, SD = 8.66, age range 70 to 103) and examined time-ordered relations between personality traits (i.e., extraversion and neuroticism) and performance-based indicators of functional health (i.e., physical and sensory functioning) in late life. Consistent with proposals to distinguish the young-old (age 70 to 84) from the oldest-old (aged 85+) in later life, results suggest that predictive effects of neuroticism on functional health are stronger in younger as compared with older individuals. In contrast, health decrements precede and predict change in neuroticism in the oldest-old more strongly as compared with the young-old. In addition, we found that decreases in extraversion predict subsequent decreases in functional health and vice versa, with effects being equally pronounced among younger and older participants. Furthermore, by employing continuous time models we could demonstrate that the magnitude of these effects varies depending upon the time interval under consideration. These findings suggest that personality and functional health are closely intertwined in old and very old age, and that the nature of time-ordered associations differs between traits and age period. We discuss conceptual and practical implications.

 

mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review.

Weichhart T.

Gerontology. 2017 Dec 1. doi: 10.1159/000484629. [Epub ahead of print]

PMID: 29190625

https://www.karger.com/Article/FullText/484629

Abstract

The mechanistic target of rapamycin (mTOR) network is an evolutionary conserved signaling hub that senses and integrates environmental and intracellular nutrient and growth factor signals to coordinate basic cellular and organismal responses such as cell growth, proliferation, apoptosis, and inflammation depending on the individual cell and tissue. A growing list of evidence suggests that mTOR signaling influences longevity and aging. Inhibition of the mTOR complex 1 (mTORC1) with rapamycin is currently the only known pharmacological treatment that increases lifespan in all model organisms studied. This review discusses the potential mechanisms how mTOR signaling controls lifespan and influences aging-related processes such as cellular senescence, metabolism, and stem cell function. Understanding these processes might provide novel therapeutic approaches to influence longevity and aging-related diseases.

KEYWORDS:

Calorie restriction; Metabolic reprogramming; Rapamycin

 

Folate and Vitamin B12-Related Biomarkers in Relation to Brain Volumes.

van der Zwaluw NL, Brouwer-Brolsma EM, van de Rest O, van Wijngaarden JP, In 't Veld PH, Kourie DI, Swart KM, Enneman AW, van Dijk SC, van der Velde N, Kessels RP, Smeets PA, Kok FJ, Dhonukshe-Rutten RA, de Groot LC.

Nutrients. 2016 Dec 24;9(1). pii: E8. doi: 10.3390/nu9010008.

PMID: 28029114 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295052/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295052/pdf/nutrients-09-00008.pdf

Abstract

AIM:

We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B12 status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin B12 supplementation with participants who did not.

METHODS:

Participants of the B-PROOF study (n = 2919) were assigned to 400 µg folic acid and 500 µg vitamin B12, or a placebo. After two years of intervention, T₁-weighted magnetic resonance imaging (MRI) scans were made in a random subsample (n = 218) to obtain grey and white matter volume, and total brain volume (TBV). Plasma homocysteine, serum folate, vitamin B12, holotranscobalamin, and methylmalonic acid concentrations were measured.

RESULTS:

Multiple linear regression analyses showed inverse associations between plasma homocysteine with TBV (β = -0.91, 95% CI -1.85-0.03; p = 0.06) and between serum folate and TBV (β = -0.20, 95% CI -0.38, -0.02; p = 0.03). No significant associations were observed for serum vitamin B12 and holotranscobalamin. Fully adjusted ANCOVA models showed that the group that received B-vitamins had a lower TBV (adjusted mean 1064, 95% CI 1058-1069 mL) than the non-supplemented group (1072, 95% CI 1067-1078 mL, p = 0.03).

CONCLUSIONS:

Results were contradictory, with higher Hcy levels associated with lower TBV, but also with higher folate levels associated with lower TBV. In addition, the lack of a baseline measurement withholds us from giving recommendations on whether folic acid and vitamin B12 supplementation will be beneficial above and beyond normal dietary intake for brain health.

KEYWORDS:

brain volume; folate; grey matter; holotranscobalamin; homocysteine; methylmalonic acid; vitamin B12; white matter

 

Study: Older Adults Better Off Lifting Weights Than Following Cardio Routine

22Nov - by Daniel Steingold

https://www.studyfinds.org/older-adults-seniors-fitness-muscle/

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Effect of Exercise Type During Intentional Weight Loss on Body Composition in Older Adults with Obesity.

Beavers KM, Ambrosius WT, Rejeski WJ, Burdette JH, Walkup MP, Sheedy JL, Nesbit BA, Gaukstern JE, Nicklas BJ, Marsh AP.

Obesity (Silver Spring). 2017 Nov;25(11):1823-1829. doi: 10.1002/oby.21977.

PMID: 29086504

Abstract

OBJECTIVE:

To examine the long-term effects of exercise modality during weight loss on body composition and associations between body composition and physical function changes.

METHODS:

Two hundred forty-nine older adults (66.9 ± 4.7 years, 71% women, 32% African American, BMI: 34.4 ± 3.7 kg/m2 ) were randomized to weight loss (WL; n = 82), WL plus aerobic training (WL + AT; n = 86), or WL plus resistance training (WL + RT; n = 81) for 18 months. Dual-energy x-ray absorptiometry-acquired body composition, 400-m walk time, and knee extensor strength were measured at baseline and at 6 and 18 months.

RESULTS:

Total body mass loss was enhanced when WL was combined with exercise (WL: -5.7 ± 0.7 kg, WL + AT: -8.5 ± 0.7 kg, WL + RT: -8.7 ± 0.7 kg; P < 0.01). Total body fat mass loss was significantly greater in WL + AT (-6.8 ± 0.6 kg, -16.4%) and WL + RT (-7.8 ± 0.5 kg, -19.0%) than WL (-4.8 ± 0.6 kg, -10.9%); both P < 0.01. Lean mass loss was greatest in WL + AT (-1.6 ± 0.3 kg, -3.1%) compared with WL + RT (-0.8 ± 0.3 kg, -1.5%) or WL (-1.0 ± 0.3 kg; -2.0%); both P ≤ 0.02. Change in 400-m walk time was associated with change in fat mass (β/SD = +6.1 s; P < 0.01), while change in knee extensor strength was associated with change in lean mass (β/SD = +1.6 Nm; P < 0.01).

CONCLUSIONS:

WL + RT results in less lean mass lost than WL + AT; WL plus exercise yields greater fat mass loss than WL alone.

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Sucrose withdrawal induces depression and anxiety-like behavior by Kir2.1 upregulation in the nucleus accumbens.

Kim S, Shou J, Abera S, Ziff EB.

Neuropharmacology. 2017 Nov 27;130:10-17. doi: 10.1016/j.neuropharm.2017.11.041. [Epub ahead of print]

PMID: 29191750

Abstract

Dieting induces depression and anxiety among other emotional symptoms. Animal models indicate that repeated access to palatable foods such as sugar induces depression and anxiety-like behavior when the food is no longer available. However, the neurobiological mechanisms of how dietary restriction influences mood have not been fully understood. We used the two-bottle sucrose choice paradigm as an overeating and withdrawal model. Withdrawal after lengthy sucrose overeating elicited depression and anxiety-like behavior, which was reversed by sucrose reinstatement. In the nucleus accumbens (NAc) of sucrose withdrawal animals, dopamine levels and cAMP response element binding protein (CREB) activity were significantly reduced, while the inwardly rectifying K+ channel, Kir2.1, was significantly elevated. In addition, overexpression of Kir2.1 selectively in neurons expressing dopamine D1 receptors was sufficient to induce negative mood-linked behavior in the absence of sucrose overeating experience. As elevated K+ channels reduce neuronal excitability, a sucrose withdrawal-induced increase in Kir2.1 expression is able to decrease NAc activity, which provides a cellular basis for depression and anxiety-like behavior in animals.

KEYWORDS:

Anxiety; Depression; Dopamine; Kir2.1; Nucleus accumbens; Sucrose withdrawal

 

[The below paper is pdf-availed.]

Hyperactivity of The Sympatho-Adrenomedullary System Without Any Modification of The Hypothalamic-Pituitary-Adrenal Axis Following Food Restriction Among High-Level Weightlifters.

Durguerian A, Filaire E, Drogou C, Sauvet F, Bougard C, Chennaoui M.

J Strength Cond Res. 2017 Nov 29. doi: 10.1519/JSC.0000000000002038. [Epub ahead of print]

PMID: 29194183

Abstract

We examined the effects of six days of food restriction on salivary α-amylase (sAA), cortisol and dehydroepiandrostenedione (DHEA) awakening responses, psychological parameters and performance among eleven international weightlifters. Assessments were made at baseline (T1) and 6 days after a normal period of training while maintaining body weight (T2). Then, participants were assigned into two groups depending on whether they lost (Diet group) or maintained (Control group) their body weight. Anthropometric, psychological, physical and physiological assessments were also realized 6 days (T3) following the restricted dietary period for the Diet group. Food restriction (T3) induced a significant rise of sAA awakening response (364.6%, p < 0.05), while no significant variations were observed among the HPA axis (cortisol and DHEA). Significant alterations of the general Recovery Score and General stress Score, evaluated through the Recovery-Stress Questionnaire for athletes, were noted following food restriction. Weightlifting performance, evaluated during a simulated weightlifting competition, was maintained after the 6-d food restriction; we even noted an increased weightlifting performance related to body weight (Sinclair coefficient). Our findings support the hypothesis that food restriction induces a challenging situation to the organism, resulting in an asymmetry between the two stress systems activation. These results reinforce the necessity to cautiously plan and monitor the weight regulation process before competition to avoid potential negative outcomes on psychophysiological parameters. In this regard, the psychobiological approach, especially the awakening responses, seems a useful tool.

 

Low protein intake, muscle strength and physical performance in the very old: The Newcastle 85+ Study.

Granic A, Mendonça N, Sayer AA, Hill TR, Davies K, Adamson A, Siervo M, Mathers JC, Jagger C.

Clin Nutr. 2017 Nov 16. pii: S0261-5614(17)31403-6. doi: 10.1016/j.clnu.2017.11.005. [Epub ahead of print]

PMID: 29191494

http://www.sciencedirect.com/science/article/pii/S0261561417314036

Abstract

BACKGROUND:

Low protein intake has been linked to reduced muscle strength and physical performance in older adults but little is known about how it may affect muscle health and subsequent functional decline in the very old (aged 85+), who are at enhanced risk of malnutrition and loss of muscle mass and strength.

AIMS:

To investigate the associations between low protein intake, defined as the intake of <1 g protein/kg adjusted body weight/day (<1 g/kg aBW/d) and decline in muscle strength and physical performance in the very old.

METHODS:

The analytic sample consisted of 722 community-dwelling participants (60% women) from the Newcastle 85+ Study who had protein intake at baseline. Participants were followed-up for change in grip strength (GS) and Timed Up-and-Go (TUG) test over 5 years (baseline, 18, 36, and 60 months). We used mixed models to determine the effects of low protein intake on muscle strength and physical performance in all participants, and also stratified by sex.

RESULTS:

At baseline, 390 (54%) participants (261 women, p < 0.001) reported low protein intake, and these differed from participants with good intake (≥1 g/kg aBW/d) on several measures of health and function. In the model adjusted for protein intake, consuming <1 g/kg aBW/d of protein was associated with a 1.62 kg lower GS (p = 0.008) in all participants, and especially in women (β (SE) = -0.83 (0.41), p = 0.05) after adjusting for key baseline covariates (anthropometry, multimorbidity, arthritis in hands, cognitive status and physical activity). The rate of decline in GS over 5 years was not associated with protein intake. Women, but not men, with low protein intake had worse baseline TUG (β (SE) = 0.04 (0.02), p = 0.03) compared with those with good protein intake in the fully adjusted model, but the rate of decline in TUG was not affected by daily protein status.

CONCLUSIONS:

Intake of <1 g protein/kg aBW/d may negatively affect muscle strength and physical performance in late life, especially in older women, independently of important covariates. More research is needed in the very old to define the optimal protein intake for maintenance of muscle health and function.

Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

KEYWORDS:

Aged 80 and over; Grip strength; Low protein intake; Newcastle 85+ Study; Physical activity; Timed Up-and-Go test

 

[The below paper is pdf-availed.]

Cereal fiber, fruit fiber, and type 2 diabetes: Explaining the paradox.

Davison KM, Temple NJ.

J Diabetes Complications. 2017 Nov 10. pii: S1056-8727(17)30812-7. doi: 10.1016/j.jdiacomp.2017.11.002. [Epub ahead of print] Review.

PMID: 29191432

Abstract

While the relationship between dietary fiber and type 2 diabetes mellitus (T2DM) has been much studied, the evidence about its role in the prevention and control of this condition has been conflicting. We critically evaluate prospective cohort studies and randomized controlled trials (RCTs) that examined insoluble/nonviscous/cereal fiber and soluble/viscous/fruit fiber in relation to risk of T2DM. Taken as a whole this evidence indicates that, in the quantities typically eaten, cereal fiber is protective against T2DM while fruit fiber gives little protection. We argue that the protective action of cereal fiber may be explained by the modulating effects of gut microbiota through mechanisms such as: 1) improving glucose tolerance via energy metabolism pathways (colonic fermentation and generation of short-chain fatty acids); 2) reducing inflammation; and 3) altering the immune response. By gaining more knowledge of specific host and gut microbial functional pathways involved in T2DM development and the potential role of cereal fiber, appropriate disease prevention and intervention strategies may be developed.

KEYWORDS:

Cereal fiber; Diabetes; Dietary fiber; Microbiome; Type 2 diabetes

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Dietary fibre and incidence of type 2 diabetes in eight European countries: the EPIC-InterAct Study and a meta-analysis of prospective studies.

InterAct Consortium.

Diabetologia. 2015 Jul;58(7):1394-408. doi: 10.1007/s00125-015-3585-9. Epub 2015 May 29.

PMID: 26021487 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472947/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472947/pdf/125_2015_Article_3585.pdf

Abstract

AIMS/HYPOTHESIS:

Intake of dietary fibre has been associated with a reduced risk of type 2 diabetes, but few European studies have been published on this. We evaluated the association between intake of dietary fibre and type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study and in a meta-analysis of prospective studies.

METHODS:

During 10.8 years of follow-up, 11,559 participants with type 2 diabetes were identified and a subcohort of 15,258 participants was selected for the case-cohort study. Country-specific HRs were estimated using Prentice-weighted Cox proportional hazards models and were pooled using a random effects meta-analysis. Eighteen other cohort studies were identified for the meta-analysis.

RESULTS:

In the EPIC-InterAct Study, dietary fibre intake was associated with a lower risk of diabetes (HRQ4 vs Q1 0.82; 95% CI 0.69, 0.97) after adjustment for lifestyle and dietary factors. Similar inverse associations were observed for the intake of cereal fibre and vegetable fibre, but not fruit fibre. The associations were attenuated and no longer statistically significant after adjustment for BMI. In the meta-analysis (19 cohorts), the summary RRs per 10 g/day increase in intake were 0.91 (95% CI 0.87, 0.96) for total fibre, 0.75 (95% CI 0.65, 0.86) for cereal fibre, 0.95 (95% CI 0.87, 1.03) for fruit fibre and 0.93 (95% CI 0.82, 1.05) for vegetable fibre.

CONCLUSIONS/INTERPRETATION:

The overall evidence indicates that the intake of total and cereal fibre is inversely related to the risk of type 2 diabetes. The results of the EPIC-InterAct Study suggest that the association may be partially explained by body weight.

 

Effects of melatonin supplementation on blood lipid concentrations: A systematic review and meta-analysis of randomized controlled trials.

Mohammadi-Sartang M, Ghorbani M, Mazloom Z.

Clin Nutr. 2017 Nov 16. pii: S0261-5614(17)31401-2. doi: 10.1016/j.clnu.2017.11.003. [Epub ahead of print]

PMID: 29191493

Abstract

BACKGROUND & AIMS:

Melatonin supplementation may be associated with blood lipids improvement; however, the current evidence from randomized controlled trials (RCTs) is inconsistent. The present study aimed to systematically review and analyze RCTs assessing the effects of melatonin supplementation on blood lipids.

METHODS:

A comprehensive literature search in several database was performed up to January 2017. Quantitative data synthesis was performed using a fixed or random-effects model, with weight mean difference (WMD) and 95% confidence intervals (CI). Standard methods were used for assessment of heterogeneity, meta-regression, sensitivity analysis and publication bias.

RESULTS:

A total of 8 RCTs were eligible. Meta-analysis suggested a significant association between melatonin supplementation and a reduction in triglycerides (WMD: -31.54 mg/dL, 95% CI: -50.71, -12.38, p = 0.001), and total cholesterol levels (WMD: -18.48 mg/dL, 95% CI: -35.33, -1.63, p = 0.032), while no significant effect on LDL-C (WMD: -2.37 mg/dL, 95% CI: -11.61, -6.86, p = 0.615) and HDL-C (WMD: 1.28 mg/dL, 95% CI: -0.66, 3.23, p = 0.197) was found. In sub-group analysis, a significant decrease in triglycerides was found at doses ≥8 mg/d and when trials last ≥8 weeks. In addition, a significant decrease of total cholesterol was found at doses ≥8 mg/d and when total cholesterol baseline levels were ≥200 mg/dL.

CONCLUSIONS:

Melatonin supplementation has significant effects on triglycerides and total cholesterol levels, which was more evident in higher dose and longer duration and also in a higher concentration of cholesterol levels. Further studies are required to determine the benefits of melatonin on lipid profile.

Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

KEYWORDS:

Cholesterol; HDL-cholesterol; LDL-cholesterol; Melatonin; Triglycerides

 

Body Mass Index and Vascular Disease in Men Aged 65 Years and Over: HIMS (Health In Men Study).

Lacey B, Yeap BB, Golledge J, Lewington S, McCaul KA, Norman PE, Flicker L, Almeida OP, Hankey GJ.

J Am Heart Assoc. 2017 Nov 27;6(12). pii: e007343. doi: 10.1161/JAHA.117.007343.

PMID: 29180456 Free Article

http://jaha.ahajournals.org/content/6/12/e007343.long

Abstract

BACKGROUND:

Understanding the relationship between body mass index (BMI) and vascular disease at older age has become increasingly important in the many countries where both average age and BMI are rising.

METHODS AND RESULTS:

In this prospective cohort study, 12 203 men (aged ≥65) were recruited in 1996-1999 from the general population in Perth, Australia. To limit reverse causality, analyses excluded those with past vascular disease and the first 4 years of follow-up. During a further 8 (SD3) years of follow-up, there were 1136 first-ever major vascular events (nonfatal myocardial infarction, nonfatal stroke, or death from any vascular cause). Cox regression (adjusted for age, education, and smoking) related BMI at recruitment to incidence of major vascular events. At ages 65 to 94, the lowest risk of major vascular events was at ≈ 22.5 to 25 kg/m2. In the higher BMI range (≥25 kg/m2), 5 kg/m2 higher BMI was associated with 33% higher risk of major vascular events (hazard ratio, 1.33 [95% confidence interval, 1.18-1.49]): 24% higher risk of ischemic heart disease (1.24 [1.06-1.46]); 34% higher risk of stroke (1.34 [1.11-1.63]); and 78% higher risk of other vascular death (1.78 [1.32-2.41]). In the lower BMI range, there were fewer events and no strong evidence of an association (hazard ratio per 5 kg/m2 higher BMI, 0.82 [95% confidence interval, 0.61-1.12]).

CONCLUSIONS:

In this population of older men, risk of major vascular events was lowest at ≈ 22.5 to 25 kg/m2. Above this range, BMI was strongly related to incidence of major vascular events, with each 5 kg/m2 higher BMI associated with ≈30% higher risk.

KEYWORDS:

adiposity; body mass index; epidemiology; ischemic heart disease; stroke; vascular disease

 

Effects of Dark Chocolate and Almonds on Cardiovascular Risk Factors in Overweight and Obese Individuals: A Randomized Controlled-Feeding Trial.

Lee Y, Berryman CE, West SG, Chen CO, Blumberg JB, Lapsley KG, Preston AG, Fleming JA, Kris-Etherton PM.

J Am Heart Assoc. 2017 Nov 29;6(12). pii: e005162. doi: 10.1161/JAHA.116.005162.

PMID: 29187388 Free Article

http://jaha.ahajournals.org/content/6/12/e005162.long

Abstract

BACKGROUND:

Consumption of almonds or dark chocolate and cocoa has favorable effects on markers of coronary heart disease; however, the combined effects have not been evaluated in a well-controlled feeding study. The aim of this study was to examine the individual and combined effects of consumption of dark chocolate and cocoa and almonds on markers of coronary heart disease risk.

METHODS AND RESULTS:

A randomized controlled, 4-period, crossover, feeding trial was conducted in overweight and obese individuals aged 30 to 70 years. Forty-eight participants were randomized, and 31 participants completed the entire study. Each diet period was 4 weeks long, followed by a 2-week compliance break. Participants consumed each of 4 isocaloric, weight maintenance diets: (1) no treatment foods (average American diet), (2) 42.5 g/d of almonds (almond diet [ALD]), (3) 18 g/d of cocoa powder and 43 g/d of dark chocolate (chocolate diet [CHOC]), or (4) all 3 foods (CHOC+ALD). Compared with the average American diet, total cholesterol, non-high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol after the ALD were lower by 4%, 5%, and 7%, respectively (P<0.05). The CHOC+ALD decreased apolipoprotein B by 5% compared with the average American diet. For low-density lipoprotein subclasses, compared with the average American diet, the ALD showed a greater reduction in large buoyant low-density lipoprotein particles (-5.7±2.3 versus -0.3±2.3 mg/dL; P=0.04), whereas the CHOC+ALD had a greater decrease in small dense low-density lipoprotein particles (-12.0±2.8 versus -5.3±2.8 mg/dL; P=0.04). There were no significant differences between diets for measures of vascular health and oxidative stress.

CONCLUSIONS:

Our results demonstrate that consumption of almonds alone or combined with dark chocolate under controlled-feeding conditions improves lipid profiles. Incorporating almonds, dark chocolate, and cocoa into a typical American diet without exceeding energy needs may reduce the risk of coronary heart disease.

CLINICAL TRIAL REGISTRATION:

URL: https://www.clinicaltrials.gov. Unique identifier: NCT01882881.

KEYWORDS:

almonds; cardiovascular disease risk factors; dark chocolate; flow‐mediated dilation; lipids and lipoproteins

 

Visit-to-Visit Variability of Fasting Plasma Glucose and the Risk of Cardiovascular Disease and All-Cause Mortality in the General Population.

Wang A, Liu X, Xu J, Han X, Su Z, Chen S, Zhang N, Wu S, Wang Y, Wang Y.

J Am Heart Assoc. 2017 Nov 29;6(12). pii: e006757. doi: 10.1161/JAHA.117.006757.

PMID: 29187392 Free Article

http://jaha.ahajournals.org/content/6/12/e006757.long

Abstract

BACKGROUND:

The association of short-term variability of fasting plasma glucose (FPG) and mortality has been well investigated. However, the relationships between visit-to-visit variability of FPG over longer periods of follow-up and cardiovascular disease (CVD) and all-cause mortality are unclear. This study aimed to investigate these relationships.

METHODS AND RESULTS:

The current analysis included 53 607 Chinese participants (mean age, 49.10 years) who were free of CVD in the Kailuan study. Participants were divided into 4 categories by quartiles of visit-to-visit variability of FPG. Visit-to-visit variability of FPG was defined as the coefficient of variation of 3 values of FPG that were measured from the examination periods of 2006 to 2007, 2008 to 2009, and 2010 to 2011. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for CVD and all-cause mortality. After a mean follow-up of 4.93 years, 4261 individuals developed CVD and 1545 individuals died. The incidence of CVD and all-cause mortality was 5.04 and 5.85 per 1000 person-years, respectively. After adjusting for mean FPG and other potential confounders, individuals in the highest quartile of variability of FPG compared with participants in the lowest quartile showed a 26% greater risk of developing CVD (hazard ratio, 1.26; 95% confidence interval, 1.08-1.47) and a 46% greater risk for all-cause mortality (hazard ratio, 1.46; 95% confidence interval, 1.25-1.70).

CONCLUSIONS:

Independent of mean FPG and other baseline parameters, elevated visit-to-visit variability of FPG significantly increases the risk of CVD and all-cause mortality in the general population. Measuring long-term visit-to-visit variability of FPG is helpful for predicting the risk for CVD and all-cause mortality.

KEYWORDS:

all‐cause mortality; cardiovascular events; death; glucose; variability; visit‐to‐visit

 

Cadmium, Carotid Atherosclerosis, and Incidence of Ischemic Stroke

Yan Borné, Björn Fagerberg, Margaretha Persson, Gerd Östling, Martin Söderholm, Bo Hedblad, Gerd Sallsten, Lars Barregard, Gunnar Engström

Journal of the American Heart Association. 2017;6:e006415, originally published December 2, 2017

https://doi.org/10.1161/JAHA.117.006415

http://jaha.ahajournals.org/content/6/12/e006415

Abstract

Background Exposure to cadmium has been associated with carotid plaques, inflammation in carotid plaques, and increased risk of ischemic stroke. This study examined the separate and interacting effects of blood cadmium levels and carotid plaques on the risk of incident ischemic stroke.

Methods and Results Cadmium levels were measured in 4156 subjects (39.2% men; mean±SD age 57.3±5.9 years) without history of stroke, from the Malmö Diet and Cancer cohort. The right carotid artery was examined using B‐mode ultrasound examination at baseline. Incidence of ischemic stroke was monitored over a mean follow‐up of 16.7 years. Carotid plaque was present in 34.5% of participants. Cadmium was significantly higher in subjects with plaque (mean±SD: 0.53±0.58 μg/L versus 0.42±0.49 μg/L; P<0.001). A total of 221 subjects had ischemic stroke during the follow‐up. Incidence of ischemic stroke was associated both with carotid plaque (hazard ratio 1.44, 95% confidence interval, 1.09–1.90, P=0.009) and cadmium (hazard ratio for quartile [Q] 4 versus Q1–3: 1.95, confidence interval, 1.33–2.85, P=0.001), after adjustment for risk factors. There was a significant interaction between cadmium and plaque with respect to risk of ischemic stroke (P=0.011). Adjusted for risk factors, subjects with plaque and cadmium in Q4 had a hazard ratio of 2.88 (confidence interval, 1.79–4.63) for ischemic stroke, compared with those without plaque and cadmium in Q1 to Q3.

Conclusions Cadmium was associated with incidence of ischemic stroke, both independently and in synergistic interaction with carotid plaques. This supports the hypothesis that cadmium promotes vulnerability of carotid plaques, thereby increasing the risk of rupture and ischemic stroke.

arteriosclerosiscadmiumincidenceischemic strokeplaque

Clinical Perspective

What Is New?

Blood cadmium is a risk factor for incidence of ischemic stroke, and the risk of stroke increases synergistically in the presence of carotid plaque.

What Are the Clinical Implications?

Cadmium is a toxic element that accumulates in the human body and the impact on public health could be important since many individuals are exposed.

Exposure to cadmium through diet and smoking should be minimized.

Blood cadmium could be a marker of plaque vulnerability and risk of stroke.

 

Obesity and the tumor microenvironment.

Olson OC, Quail DF, Joyce JA.

Science. 2017 Dec 1;358(6367):1130-1131. doi: 10.1126/science.aao5801. No abstract available.

PMID: 29191893

http://science.sciencemag.org/content/358/6367/1130.full

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Effects of isolated soluble fiber supplementation on body weight, glycemia, and insulinemia in adults with overweight and obesity: a systematic review and meta-analysis of randomized controlled trials.

Thompson SV, Hannon BA, An R, Holscher HD.

Am J Clin Nutr. 2017 Nov 1. pii: ajcn163246. doi: 10.3945/ajcn.117.163246. [Epub ahead of print]

PMID: 29092878 Free Article

Abstract

Background: There is strong epidemiologic evidence that dietary fiber intake is protective against overweight and obesity; however, results of intervention studies have been mixed. Soluble fiber beneficially affects metabolism, and fiber supplementation may be a feasible approach to improve body composition and glycemia in adults with overweight and obesity.Objective: We evaluated randomized controlled trials (RCTs) of isolated soluble fiber supplementation in overweight and obese adults on outcomes related to weight management [body mass index (BMI; in kg/m2), body weight, percentage of body fat, and waist circumference] and glucose and insulin metabolism (homeostasis model assessment of insulin resistance and fasting insulin) through a systematic review and meta-analysis.Design: We searched PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature and Cochrane Library databases. Eligible studies were RCTs that compared isolated soluble fiber with placebo treatments without energy-restriction protocols. Random-effects models were used to estimate pooled effect sizes and 95% CIs. Meta-regressions were performed to assess outcomes in relation to the intervention duration, fiber dose, and fiber type. Publication bias was assessed via Begg's and Egger's tests and funnel plot inspection.Results: Findings from 12 RCTs (n = 609 participants) from 2 to 17 wk of duration are summarized in this review. Soluble fiber supplementation reduced BMI by 0.84 (95% CI: -1.35, -0.32; P = 0.001), body weight by 2.52 kg (95% CI: -4.25, -0.79 kg; P = 0.004), body fat by 0.41% (95% CI: -0.58%, -0.24%; P < 0.001), fasting glucose by 0.17 mmol/L (95% CI: -0.28, -0.06 mmol/L; P = 0.002), and fasting insulin by 15.88 pmol/L (95% CI: -29.05, -2.71 pmol/L; P = 0.02) compared with the effects of placebo treatments. No publication bias was identified. Considerable between-study heterogeneity was observed for most outcomes.Conclusions: Isolated soluble fiber supplementation improves anthropometric and metabolic outcomes in overweight and obese adults, thereby indicating that supplementation may improve fiber intake and health in these individuals. However, the interpretation of these findings warrants caution because of the considerable between-study heterogeneity.

KEYWORDS:

body composition; glucose; insulin; meta-analysis; soluble fiber supplementation

 

The effects of dietary protein intake on appendicular lean mass and muscle function in elderly men: a 10-wk randomized controlled trial.

Mitchell CJ, Milan AM, Mitchell SM, Zeng N, Ramzan F, Sharma P, Knowles SO, Roy NC, Sjödin A, Wagner KH, Cameron-Smith D.

Am J Clin Nutr. 2017 Nov 1. pii: ajcn160325. doi: 10.3945/ajcn.117.160325. [Epub ahead of print]

PMID: 29092886

Abstract

Background: The Recommended Daily Allowance (RDA) for protein intake in the adult population is widely promoted as 0.8 g · kg-1 · d-1 Aging may increase protein requirements, particularly to maintain muscle mass.Objective: We investigated whether controlled protein consumption at the current RDA or twice the RDA (2RDA) affects skeletal muscle mass and physical function in elderly men.Design: In this parallel-group randomized trial, 29 men aged >70 y [mean ± SD body mass index (in kg/m2): 28.3 ± 4.2] were provided with a complete diet containing either 0.8 (RDA) or 1.6 (2RDA) g protein · kg-1 · d-1, aimed to balance energy needs. Before treatment and after 10 wk of intervention, whole-body and appendicular lean mass were measured by using dual-energy X-ray absorptiometry. Knee-extension peak power was measured with dynamometry.Results: Both groups were found to have been in a moderate negative energy balance (mean ± SD RDA: 209 ± 213 kcal/d; 2RDA 145 ± 214 kcal/d; P= 0.427 for difference between the groups). In comparison with RDA, whole-body lean mass increased in 2RDA (P = 0.001; 1.49 ± 1.30 kg, P < 0.001 compared with -0.55 ± 1.49 kg, P = 0.149). This difference was mostly accounted for by an increase in trunk lean mass found in 2RDA (+1.39 ± 1.09 kg, P < 0.001). Appendicular lean mass also decreased in RDA compared with 2RDA (P = 0.022), driven by a reduction in RDA (-0.64 ± 0.91 kg, P = 0.005 compared with 0.11 ± 0.57 kg, P = 0.592). Adjusting for energy imbalances did not alter these findings. Knee-extension peak power was also differently affected (P = 0.012; 26.6 ± 47.7 W, P = 0.015 in 2RDA compared with -11.7 ± 31.0 W, P = 0.180 in RDA).Conclusions: Consumption of a diet providing 2RDA for protein compared with the current guidelines was found to have beneficial effects on lean body mass and leg power in elderly men. These effects were not explained by differences in energy balance.

KEYWORDS:

dietary protein; nutrient requirements; older adults; skeletal muscle; whole foods

 

Muscle Protein Synthesis and Muscle Mass in Healthy Older Men.

Tome D.

J Nutr. 2017 Nov 1. pii: jn263491. doi: 10.3945/jn.117.263491. [Epub ahead of print] No abstract available.

PMID: 29093015

See corresponding articles on pages 2252 and 2262.

The age-related loss of skeletal muscle mass and function is a major public health problem. These changes have been attributed to the blunted anabolic sensitivity of the response of muscle protein to protein intake due to a disruption in the regulation of muscle protein turnover and the imbalance between protein synthesis and breakdown. Sarcopenia, the age-related pathological loss of skeletal muscle mass and muscle function, is largely related to an impaired sensitivity of muscle protein synthesis to postprandial anabolic stimuli induced by amino acids, insulin, and other protein metabolism–related nutrients and hormones (1–5). In this issue of the Journal, the articles by Chanet et al. (6), “Supplementing breakfast with a vitamin D and leucine–enriched whey protein medical nutrition drink enhances postprandial muscle protein synthesis and muscle mass in healthy older men,” and Kouw et al (7), “Protein ingestion before sleep increases overnight muscle protein synthesis rates in healthy older men: a randomized controlled trial,” address 2 nutritional strategies to improve muscle protein synthesis and muscle mass and to reduce the rate of lean and muscle mass losses in older adults.

As discussed in these 2 studies, protein ingestion during meals stimulates muscle protein synthesis and represents a main nutritional component for the maintenance of body composition and skeletal muscle mass over the life span, but different feeding strategies can improve the anabolic effect of protein. The different strategies that aim to preserve muscle mass in adults and to reduce muscle losses during aging involve the supply of an adequate quantity of high-quality protein during meals according to different patterns between meals and during the day to optimize daily muscle protein anabolism. The optimal quantity of protein to be provided to older adults remains controversial, and it was shown in some studies that prolonged protein supplementation could significantly increase protein synthesis in various older populations (8–18), whereas other studies did not detect measurable increases in muscle mass or strength (19–22). The quality of the protein is also an important component, and nutritional strategies to reduce muscle protein losses in older adults also focused on the use of high-quality protein with a high content of bioavailable indispensable amino acids and high leucine content as an anabolic signal for protein synthesis (23–27). In addition, the pattern of distribution of protein over meals can also improve muscle protein synthesis and possibly lean mass in older adults (28–31).

In addition to the importance of the quantity and quality of the protein in promoting protein synthesis, fortification with free leucine, indispensable amino acids, and other indispensable nutrients has been studied to determine its effectiveness in improving postprandial muscle protein synthesis rates when lower amounts of dietary protein are consumed. Interestingly, the importance of vitamin D in the regulation of muscle protein metabolism also has been examined, because an inadequate vitamin D status in the older population has been related to impairment of different functional outcomes related to protein anabolism and muscle mass (32–35). Accordingly, the study by Chanet et al. (6) was a randomized, placebo-controlled, double-blind study that aimed to investigate the acute effect of a vitamin D– and leucine-enriched whey protein medical nutrition drink integrated into the habitual breakfast of healthy older adults on postprandial muscle protein synthesis. In addition, the longer-term effect on muscle mass, physical performance, and glucose and insulin response to meals was evaluated. The results showed that supplementing breakfast with a vitamin D– and leucine-enriched whey protein nutrition drink stimulated postprandial muscle protein synthesis and increased muscle mass after 24 wk in healthy older adults. As discussed by the authors, the observed longer-term increase in muscle mass with the intervention is in line with the acute stimulation of postprandial muscle protein synthesis.

Not only the quantity and the quality of protein and nutrient supply matter but the pattern of protein and nutrient distribution between meals and over the day is also important in improving protein synthesis and muscle mass. Different studies have shown that the consumption of multiple meals with adequate high-quality protein content more adequately stimulates muscle protein synthesis and is positively associated with muscle protein synthesis, lean mass, and muscle performance (30, 36–41). In addition, protein ingestion before sleep has been suggested as an effective strategy for increasing the anabolic response and to efficiently stimulate muscle protein synthesis in older adults (42). Accordingly, the study by Kouw et al. (7) evaluated the efficacy of presleep protein ingestion to improve muscle protein synthesis rates during the overnight period in older adults. This study assessed in older men the efficacy of presleep ingestion of 40 g casein, 20 g casein, 20 g casein + leucine, or placebo on protein digestion and absorption kinetics and overnight muscle protein synthesis rates. The results showed that these proteins were properly digested and absorbed throughout the night and that, compared with placebo, 40 g protein before sleep increased overnight muscle protein synthesis rates above values observed in the placebo group, whereas this effect was not observed with either 20 g casein or with 20 g casein + leucine. As discussed by the authors, a proper distribution (both timing and quantity) of protein intake is essential to allow protein supplementation to improve muscle mass in older adults; and presleep protein ingestion that is associated with physical activity represents an efficient strategy to stimulate muscle protein synthesis during a period in which muscle protein synthesis rates have been shown to be typically low (42–44).

These 2 studies provide interesting directions for additional nutritional strategies to support and maintain skeletal muscle mass in older individuals. In addition to the quantity and quality of protein provided to older adults, a combination that includes supplementation with indispensable amino acids and other nutrients, intake of an even pattern of distribution of protein over meals, and protein ingestion before sleep that is associated with physical activity performed in the evening could efficiently improve the efficacy of protein utilization in older adults. More work is needed on the impact of protein intake distribution, and a more precise upper threshold of protein intake remains to be established to improve muscle protein synthesis rates in older individuals. In addition, it has not been established whether there is a direct relation between protein synthesis and muscle mass, and additional results on the long- term effects of such a strategy on body composition, lean mass, and muscle function should be provided in older adults.

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Supplementing Breakfast with a Vitamin D and Leucine-Enriched Whey Protein Medical Nutrition Drink Enhances Postprandial Muscle Protein Synthesis and Muscle Mass in Healthy Older Men.

Chanet A, Verlaan S, Salles J, Giraudet C, Patrac V, Pidou V, Pouyet C, Hafnaoui N, Blot A, Cano N, Farigon N, Bongers A, Jourdan M, Luiking Y, Walrand S, Boirie Y.

J Nutr. 2017 Aug 23. pii: jn252510. doi: 10.3945/jn.117.252510. [Epub ahead of print]

PMID: 28835387 Free Article

http://jn.nutrition.org/content/147/12/2262.long

http://jn.nutrition.org/content/147/12/2262.full.pdf+html

Abstract

Background: A promising strategy to help older adults preserve or build muscle mass is to optimize muscle anabolism through providing an adequate amount of high-quality protein at each meal.Objective: This "proof of principle" study investigated the acute effect of supplementing breakfast with a vitamin D and leucine-enriched whey protein medical nutrition drink on postprandial muscle protein synthesis and longer-term effect on muscle mass in healthy older adults.Methods: A randomized, placebo-controlled, double-blind study was conducted in 24 healthy older men [mean ± SD: age 71 ± 4 y; body mass index (in kg/m2) 24.7 ± 2.8] between September 2012 and October 2013 at the Unit of Human Nutrition, University of Auvergne, Clermont-Ferrand, France. Participants received a medical nutrition drink [test group; 21 g leucine-enriched whey protein, 9 g carbohydrates, 3 g fat, 800 IU cholecalciferol (vitamin D3), and 628 kJ] or a noncaloric placebo (control group) before breakfast for 6 wk. Mixed muscle protein fractional synthesis rate (FSR) was measured at week 0 in the basal and postprandial state, after study product intake with a standardized breakfast with the use of l-[2H5]-phenylalanine tracer methodology. The longer-term effect of the medical nutrition drink was evaluated by measurement of appendicular lean mass, representing skeletal muscle mass at weeks 0 and 6, by dual-energy X-ray absorptiometry.Results: Postprandial FSR (0-240 min) was higher in the test group than in the control group [estimate of difference (ED): 0.022%/h; 95% CI: 0.010%/h, 0.035%/h; ANCOVA, P = 0.001]. The test group gained more appendicular lean mass than the control group after 6 wk (ED: 0.37 kg; 95% CI: 0.03, 0.72 kg; ANCOVA, P = 0.035), predominantly as leg lean mass (ED: 0.30 kg; 95% CI: 0.03, 0.57 kg; ANCOVA, P = 0.034).Conclusions: Supplementing breakfast with a vitamin D and leucine-enriched whey protein medical nutrition drink stimulated postprandial muscle protein synthesis and increased muscle mass after 6 wk of intervention in healthy older adults and may therefore be a way to support muscle preservation in older people.

KEYWORDS:

leucine; muscle mass; muscle protein synthesis; protein intake; sarcopenia; vitamin D

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Protein Ingestion before Sleep Increases Overnight Muscle Protein Synthesis Rates in Healthy Older Men: A Randomized Controlled Trial.

Kouw IW, Holwerda AM, Trommelen J, Kramer IF, Bastiaanse J, Halson SL, Wodzig WK, Verdijk LB, van Loon LJ.

J Nutr. 2017 Aug 30. pii: jn254532. doi: 10.3945/jn.117.254532. [Epub ahead of print]

PMID: 28855419

Abstract

Background: The loss of skeletal muscle mass with aging has been attributed to the blunted anabolic response to protein intake. Presleep protein ingestion has been suggested as an effective strategy to compensate for such anabolic resistance.Objective: We assessed the efficacy of presleep protein ingestion on dietary protein digestion and absorption kinetics and overnight muscle protein synthesis rates in older men.Methods: In a randomized, double-blind, parallel design, 48 older men (mean ± SEM age: 72 ± 1 y) ingested 40 g casein (PRO40), 20 g casein (PRO20), 20 g casein plus 1.5 g leucine (PRO20+LEU), or a placebo before sleep. Ingestion of intrinsically l-[1-13C]-phenylalanine- and l-[1-13C]-leucine-labeled protein was combined with intravenous l-[ring-2H5]-phenylalanine and l-[1-13C]-leucine infusions during sleep. Muscle and blood samples were collected throughout overnight sleep.Results: Exogenous phenylalanine appearance rates increased after protein ingestion, but to a greater extent in PRO40 than in PRO20 and PRO20+LEU (P < 0.05). Overnight myofibrillar protein synthesis rates (based on l-[ring-2H5]-phenylalanine) were 0.033% ± 0.002%/h, 0.037% ± 0.003%/h, 0.039% ± 0.002%/h, and 0.044% ± 0.003%/h in placebo, PRO20, PRO20+LEU, and PRO40, respectively, and were higher in PRO40 than in placebo (P = 0.02). Observations were similar based on l-[1-13C]-leucine tracer (placebo: 0.047% ± 0.004%/h and PRO40: 0.058% ± 0.003%/h, P = 0.08). More protein-derived amino acids (l-[1-13C]-phenylalanine) were incorporated into myofibrillar protein in PRO40 than in PRO20 (0.033 ± 0.002 and 0.019 ± 0.002 MPE, respectively, P < 0.001) and tended to be higher than in PRO20+LEU (0.025 ± 0.002 MPE, P = 0.06).Conclusions: Protein ingested before sleep is properly digested and absorbed throughout the night, providing precursors for myofibrillar protein synthesis during sleep in healthy older men. Ingestion of 40 g protein before sleep increases myofibrillar protein synthesis rates during overnight sleep. These findings provide the scientific basis for a novel nutritional strategy to support muscle mass preservation in aging and disease.

KEYWORDS:

aging; muscle protein synthesis; protein ingestion; sarcopenia; sleep

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Physical Activity Performed in the Evening Increases the Overnight Muscle Protein Synthetic Response to Presleep Protein Ingestion in Older Men.

Holwerda AM, Kouw IW, Trommelen J, Halson SL, Wodzig WK, Verdijk LB, van Loon LJ.

J Nutr. 2016 Jul;146(7):1307-14. doi: 10.3945/jn.116.230086. Epub 2016 Jun 8.

PMID: 27281811 Free Article

http://jn.nutrition.org/content/146/7/1307.long

http://jn.nutrition.org/content/146/7/1307.full.pdf+html

Abstract

BACKGROUND:

The age-related decline in skeletal muscle mass is partly attributed to anabolic resistance to food intake. Dietary protein ingestion before sleep could be used as a nutritional strategy to compensate for anabolic resistance.

OBJECTIVE:

The present study assessed whether physical activity performed in the evening can augment the overnight muscle protein synthetic response to presleep protein ingestion in older men.

METHODS:

In a parallel group design, 23 healthy older men (mean ± SEM age: 71 ± 1 y) were randomly assigned to ingest 40 g protein intrinsically labeled with l-[1-(13)C]-phenylalanine and l-[1-(13)C]-leucine before going to sleep with (PRO+EX) or without (PRO) performing physical activity earlier in the evening. Overnight protein digestion and absorption kinetics and myofibrillar protein synthesis rates were assessed by combining primed, continuous infusions of l-[ring-(2)H5]-phenylalanine, l-[1-(13)C]-leucine, and l-[ring-(2)H2]-tyrosine with the ingestion of intrinsically labeled casein protein. Muscle and blood samples were collected throughout overnight sleep.

RESULTS:

Protein ingested before sleep was normally digested and absorbed, with 54% ± 2% of the protein-derived amino acids appearing in the circulation throughout overnight sleep. Overnight myofibrillar protein synthesis rates were 31% (0.058% ± 0.002%/h compared with 0.044% ± 0.003%/h; P < 0.01; based on l-[ring-(2)H5]-phenylalanine) and 27% (0.074% ± 0.004%/h compared with 0.058% ± 0.003%/h; P < 0.01; based on l-[1-(13)C]-leucine) higher in the PRO+EX than in the PRO treatment. More dietary protein-derived amino acids were incorporated into de novo myofibrillar protein during overnight sleep in PRO+EX than in PRO treatment (0.042 ± 0.002 compared with 0.033 ± 0.002 mole percent excess; P < 0.05).

CONCLUSIONS:

Physical activity performed in the evening augments the overnight muscle protein synthetic response to presleep protein ingestion and allows more of the ingested protein-derived amino acids to be used for de novo muscle protein synthesis during overnight sleep in older men.

KEYWORDS:

dietary protein; exercise; muscle protein synthesis; overnight; sarcopenia

 

Long-Term Intake of a High-Protein Diet Affects Body Phenotype, Metabolism, and Plasma Hormones in Mice.

Vu JP, Luong L, Parsons WF, Oh S, Sanford D, Gabalski A, Lighton JR, Pisegna JR, Germano PM.

J Nutr. 2017 Oct 25. pii: jn257873. doi: 10.3945/jn.117.257873. [Epub ahead of print]

PMID: 29070713

Abstract

Background: High-protein diets (HPDs) recently have been used to obtain body weight and fat mass loss and expand muscle mass. Several studies have documented that HPDs reduce appetite and food intake.Objective: Our goal was to determine the long-term effects of an HPD on body weight, energy intake and expenditure, and metabolic hormones.Methods: Male C57BL/6 mice (8 wk old) were fed either an HPD (60% of energy as protein) or a control diet (CD; 20% of energy as protein) for 12 wk. Body composition and food intakes were determined, and plasma hormone concentrations were measured in mice after being fed and after overnight feed deprivation at several time points.Results: HPD mice had significantly lower body weight (in means ± SEMs; 25.73 ± 1.49 compared with 32.5 ± 1.31 g; P = 0.003) and fat mass (9.55% ± 1.24% compared with 15.78% ± 2.07%; P = 0.05) during the first 6 wk compared with CD mice, and higher lean mass throughout the study starting at week 2 (85.45% ± 2.25% compared with 75.29% ± 1.90%; P = 0.0001). Energy intake, total energy expenditure, and respiratory quotient were significantly lower in HPD compared with CD mice as shown by cumulative energy intake and eating rate. Water vapor was significantly higher in HPD mice during both dark and light phases. In HPD mice, concentrations of leptin [feed-deprived: 41.31 ± 11.60 compared with 3041 ± 683 pg/mL (P = 0.0004); postprandial: 112.5 ± 102.0 compared with 8273 ± 1415 pg/mL (P < 0.0001)] and glucagon-like peptide 1 (GLP-1) [feed-deprived: 5.664 ± 1.44 compared with 21.31 ± 1.26 pg/mL (P = <0.0001); postprandial: 6.54 ± 2.13 compared with 50.62 ± 11.93 pg/mL (P = 0.0037)] were significantly lower, whereas postprandial glucagon concentrations were higher than in CD-fed mice.Conclusions: In male mice, the 12-wk HPD resulted in short-term body weight and fat mass loss, but throughout the study preserved body lean mass and significantly reduced energy intake and expenditure as well as leptin and GLP-1 concentrations while elevating postprandial glucagon concentrations. This study suggests that long-term use of HPDs may be an effective strategy to decrease energy intake and expenditure and to maintain body lean mass.

KEYWORDS:

appetite and energy intake; high-protein diet; metabolic hormones; metabolism and energy expenditure; respirometry and calorimetry

 

Increased Protein Consumption during the Day from an Energy-Restricted Diet Augments Satiety but Does Not Reduce Daily Fat or Carbohydrate Intake on a Free-Living Test Day in Overweight Women.

Gwin JA, Maki KC, Leidy HJ.

J Nutr. 2017 Oct 25. pii: jn255554. doi: 10.3945/jn.117.255554. [Epub ahead of print]

PMID: 29070709

Abstract

Background: Higher-protein (HP) energy-restriction diets improve weight management to a greater extent than normal-protein (NP) versions. Potential mechanisms of action with regard to assessment of eating behaviors across the day have not been widely examined during energy restriction.Objectives: The objectives of this study were to test whether the consumption of an HP energy-restriction diet reduces carbohydrate and fat intakes through improvements in daily appetite, satiety, and food cravings compared with NP versions and to test whether protein type within the NP diets alters protein-related satiety.Methods: Seventeen overweight women [mean ± SEM age: 36 ± 1 y; body mass index (kg/m2): 28.4 ± 0.1] completed a randomized, controlled-feeding crossover study. Participants were provided with the following ∼1250-kcal/d energy-restricted (-750-kcal/d deficit) diets, each for 6 d: HP [124 g protein/d; 60% from beef and 40% from plant sources (HP-BEEF)] or NP (48 g protein/d) that was protein-type matched (NP-BEEF) or unmatched [100% from plant-based sources (NP-PLANT)]. On day 6 of each diet period, participants completed a 12-h testing day containing repetitive appetite, satiety, and food-craving questionnaires. On day 7, the participants were asked to consume their protein requirement within each respective diet but were provided with a surplus of carbohydrate- and fat-rich foods to consume, ad libitum, at each eating occasion across the day. All outcomes reported were primary study outcomes.Results: The HP-BEEF diet reduced daily hunger by 16%, desire to eat by 15%, prospective food consumption by 14%, and fast-food cravings by 15% but increased daily fullness by 25% compared with the NP-BEEF and NP-PLANT diets (all P < 0.05). However, consuming more protein throughout the day did not reduce the energy consumed ad libitum from the fat- and carbohydrate-rich foods (HP-BEEF: 2000 ± 180 kcal/d; NP-BEEF: 2120 ± 190 kcal/d; NP-PLANT: 2070 ± 180 kcal/d). None of the outcomes differed between the NP-BEEF and NP-PLANT treatments.Conclusions: Although appetite control, satiety, and food cravings improved after an HP energy-restriction diet, increased protein consumption did not reduce carbohydrate and fat intakes throughout the free-living test day in overweight healthy women exposed to highly palatable foods.

KEYWORDS:

ad libitum; energy restriction; food choice; high-protein diets; satiety

 

l-Serine Enhances Light-Induced Circadian Phase Resetting in Mice and Humans.

Yasuo S, Iwamoto A, Lee SI, Ochiai S, Hitachi R, Shibata S, Uotsu N, Tarumizu C, Matsuoka S, Furuse M, Higuchi S.

J Nutr. 2017 Oct 25. pii: jn255380. doi: 10.3945/jn.117.255380. [Epub ahead of print]

PMID: 29070712

Abstract

Background: The circadian clock is modulated by the timing of ingestion or food composition, but the effects of specific nutrients are poorly understood.Objective: We aimed to identify the amino acids that modulate the circadian clock and reset the light-induced circadian phase in mice and humans.Methods: Male CBA/N mice were orally administered 1 of 20 l-amino acids, and the circadian and light-induced phase shifts of wheel-running activity were analyzed. Antagonists of several neurotransmitter pathways were injected before l-serine administration, and light-induced phase shifts were analyzed. In addition, the effect of l-serine on the light-induced phase advance was investigated in healthy male students (mean ± SD age 22.2 ± 1.8 y) by using dim-light melatonin onset (DLMO) determined by saliva samples as an index of the circadian phase.Results: l-Serine administration enhanced light-induced phase shifts in mice (1.86-fold; P < 0.05). Both l-serine and its metabolite d-serine, a coagonist of N-methyl-d-aspartic acid (NMDA) receptors, exerted this effect, but d-serine concentrations in the hypothalamus did not increase after l-serine administration. The effect of l-serine was blocked by picrotoxin, an antagonist of γ-aminobutyric acid A receptors, but not by MK801, an antagonist of NMDA receptors. l-Serine administration altered the long-term expression patterns of clock genes in the suprachiasmatic nuclei. After advancing the light-dark cycle by 6 h, l-serine administration slightly accelerated re-entrainment to the shifted cycle. In humans, l-serine ingestion before bedtime induced significantly larger phase advances of DLMO after bright-light exposure during the morning (means ± SEMs-l-serine: 25.9 ± 6.6 min; placebo: 12.1 ± 7.0 min; P < 0.05).Conclusion: These results suggest that l-serine enhances light-induced phase resetting in mice and humans, and it may be useful for treating circadian disturbances.

KEYWORDS:

GABA receptor; NMDA receptor; amino acids; chrononutrition; circadian clock; clock genes; dim-light melatonin onset

 

Muscling out from under the yolk of the egg's "bad" reputation.

Phillips SM.

Am J Clin Nutr. 2017 Nov 8. pii: ajcn169615. doi: 10.3945/ajcn.117.169615. [Epub ahead of print] No abstract available.

PMID: 29117968

>>>>>>>>>>>>>>>>>>>>>>

Consumption of whole eggs promotes greater stimulation of postexercise muscle protein synthesis than consumption of isonitrogenous amounts of egg whites in young men.

van Vliet S, Shy EL, Abou Sawan S, Beals JW, West DW, Skinner SK, Ulanov AV, Li Z, Paluska SA, Parsons CM, Moore DR, Burd NA.

Am J Clin Nutr. 2017 Oct 4. pii: ajcn159855. doi: 10.3945/ajcn.117.159855. [Epub ahead of print]

PMID: 28978542

Abstract

Background: Protein in the diet is commonly ingested from whole foods that contain various macro- and micronutrients. However, the effect of consuming protein within its natural whole-food matrix on postprandial protein metabolism remains understudied in humans.Objective: We aimed to compare the whole-body and muscle protein metabolic responses after the consumption of whole eggs with egg whites during exercise recovery in young men.Design: In crossover trials, 10 resistance-trained men [aged 21 ± 1 y; 88 ± 3 kg; body fat: 16% ± 1% (means ± SEMs)] received primed continuous l-[ring-2H5]phenylalanine and l-[1-13C]leucine infusions and performed a single bout of resistance exercise. After exercise, participants consumed intrinsically l-[5,5,5-2H3]leucine-labeled whole eggs (18 g protein, 17 g fat) or egg whites (18 g protein, 0 g fat). Repeated blood and muscle biopsy samples were collected to assess whole-body leucine kinetics, intramuscular signaling, and myofibrillar protein synthesis.Results: Plasma appearance rates of protein-derived leucine were more rapid after the consumption of egg whites than after whole eggs (P = 0.01). Total plasma availability of leucine over the 300-min postprandial period was similar (P= 0.75) between the ingestion of whole eggs (68% ± 1%) and egg whites (66% ± 2%), with no difference in whole-body net leucine balance (P = 0.27). Both whole-egg and egg white conditions increased the phosphorylation of mammalian target of rapamycin complex 1, ribosomal protein S6 kinase 1, and eukaryotic translation initiation factor 4E-binding protein 1 during postexercise recovery (all P < 0.05). However, whole-egg ingestion increased the postexercise myofibrillar protein synthetic response to a greater extent than did the ingestion of egg whites (P= 0.04).Conclusions: We show that the ingestion of whole eggs immediately after resistance exercise resulted in greater stimulation of myofibrillar protein synthesis than did the ingestion of egg whites, despite being matched for protein content in young men. Our data indicate that the ingestion of nutrient- and protein-dense foods differentially stimulates muscle anabolism compared with protein-dense foods.

KEYWORDS:

amino acid transporters; anabolic signaling; exercise; food protein quality; leucine; protein digestion

 

Carbohydrate Taste Sensitivity Is Associated with Starch Intake and Waist Circumference in Adults.

Low JY, Lacy KE, McBride RL, Keast RS.

J Nutr. 2017 Oct 25. pii: jn254078. doi: 10.3945/jn.117.254078. [Epub ahead of print]

PMID: 29070710 Free Article

http://jn.nutrition.org/content/147/12/2235.long

http://jn.nutrition.org/content/147/12/2235.full.pdf+html

Abstract

Background: Recent studies have proposed that humans may perceive complex carbohydrates and that sensitivity to simple carbohydrates is independent of sensitivity to complex carbohydrates. Variation in oral complex carbohydrate sensitivity may influence food consumption.Objective: This study aimed to investigate the associations between oral complex carbohydrate sensitivity, anthropometry, and dietary intake in adults.Methods: We assessed oral sensitivity to complex carbohydrates (maltodextrin and oligofructose) by measuring detection thresholds (DTs) and suprathreshold intensity perceptions (STs) for 34 participants, including 16 men (mean ± SEM age : 26.2 ± 0.4 y; range: 24-30 y) and 18 women (age: 29.4 ± 2.1 y; range: 24-55 y). We also measured height, weight, and waist circumference (WC) and participants completed a 4-d food diary and a food-frequency questionnaire.Results: Measurements of oral sensitivity to complex carbohydrates were significantly correlated with WC and dietary energy and starch intakes (DT: r = -0.38, P < 0.05; ST: r = 0.36-0.48, P < 0.05). When participants were grouped into tertiles, there were significant differences in WC and total energy or starch intakes for those who were more sensitive or experienced high intensity compared with those who were less sensitive or experienced low intensity. Being more sensitive or experiencing high intensity was associated with greater energy (7968-8954 kJ/d) and starch (29.1-29.8% of energy) intakes and a greater WC (88.2-91.4 cm) than was being less sensitive or experiencing low intensity (6693-7747 kJ/d, 20.9-22.2% of energy, and 75.5-80.5 cm, respectively).Conclusion: Complex carbohydrate sensing is associated with WC and consumption of complex carbohydrates and energy in adults. This trial was registered at anzctr.org.au as ACTRN12616001356459.

KEYWORDS:

carbohydrate taste; detection thresholds; dietary intake; glucose oligomers; glucose polymer; maltodextrin; oligosaccharides; starch taste; sweet taste; taste intensity

 

Rats sniffing out landmines speed up process of a mine-free world

Rats are also being trained to sniff out tuberculosis

CBC News Posted: Nov 30, 2017

http://www.cbc.ca/news/politics/rats-ottawa-treaty-landines-1.4425538

 

The Scientist » News & Opinion » News Analysis

A Growing Open Access Toolbox

Legal methods to retrieve paywalled articles for free are on the rise, but better self-archiving practices could help improve accessibility.

By Diana Kwon | November 28, 2017

https://www.the-scientist.com/?articles.view/articleNo/51048/title/A-Growing-Open-Access-Toolbox/&utm_campaign=NEWSLETTER_TS_The-Scientist-Daily_2016&utm_source=hs_email&utm_medium=email&utm_content=58944559&_hsenc=p2ANqtz-95TXdnk1v2v0Uw11RAHNhoiuHNgjOYg-zpeGN-CjsVp4MilZXaBlZP5SoF5SxUs3MZKKemq4RRZAsJs2Z8O-t2ikaipA&_hsmi=58944559

https://kopernio.com/

http://unpaywall.org/

[e.g.:

[The below paper is not pdf-availed.]

Food Groups and Risk of Hypertension: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies.

Schwingshackl L, Schwedhelm C, Hoffmann G, Knüppel S, Iqbal K, Andriolo V, Bechthold A, Schlesinger S, Boeing H.

Adv Nutr. 2017 Nov 15;8(6):793-803. doi: 10.3945/an.117.017178. Print 2017 Nov. Review.

PMID: 29141965

https://www.crsociety.org/topic/11801-als-papers-citations-and-possibly-links-and-excerpts-or-my-synopses/page-18

http://advances.nutrition.org/content/8/6/793.long

]

 

Towards natural mimetics of metformin and rapamycin.

Aliper A, Jellen L, Cortese F, Artemov A, Karpinsky-Semper D, Moskalev A, Swick AG, Zhavoronkov A.

Aging (Albany NY). 2017 Nov 15. doi: 10.18632/aging.101319. [Epub ahead of print]

PMID: 29165314 Free Article

http://www.aging-us.com/article/101319/text

Abstract

Aging is now at the forefront of major challenges faced globally, creating an immediate need for safe, widescale interventions to reduce the burden of chronic disease and extend human healthspan. Metformin and rapamycin are two FDA-approved mTOR inhibitors proposed for this purpose, exhibiting significant anti-cancer and anti-aging properties beyond their current clinical applications. However, each faces issues with approval for off-label, prophylactic use due to adverse effects. Here, we initiate an effort to identify nutraceuticals-safer, naturally-occurring compounds-that mimic the anti-aging effects of metformin and rapamycin without adverse effects. We applied several bioinformatic approaches and deep learning methods to the Library of Integrated Network-based Cellular Signatures (LINCS) dataset to map the gene- and pathway-level signatures of metformin and rapamycin and screen for matches among over 800 natural compounds. We then predicted the safety of each compound with an ensemble of deep neural network classifiers. The analysis revealed many novel candidate metformin and rapamycin mimetics, including allantoin and ginsenoside (metformin), epigallocatechin gallate and isoliquiritigenin (rapamycin), and withaferin A (both). Four relatively unexplored compounds also scored well with rapamycin. This work revealed promising candidates for future experimental validation while demonstrating the applications of powerful screening methods for this and similar endeavors.

KEYWORDS:

compound screening; deep learning; geroprotector; metformin; natural; nutraceutical; rapamycin

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"The study group received a 37–40% fructose diet."

Effect of a Carbohydrate-Rich Diet on Rat Detrusor Smooth Muscle Contractility: An Experimental Study.

Bolat MS, Bilge SS, Akdeniz E, Cinar O, Firat F, Agri AE, Bakirtas M, Alici O, Erdemir F.

Biomed Res Int. 2017;2017:5796456. doi: 10.1155/2017/5796456. Epub 2017 Oct 19.

PMID: 29201908

https://www.hindawi.com/journals/bmri/2017/5796456/

Abstract

OBJECTIVES:

We aimed to investigate the effect of a carbohydrate-rich diet on detrusor contractility in rats.

MATERIALS AND METHODS:

Sprague-Dawley rats were randomized into two groups. The control group received regular food and water. The study group received carbohydrate-rich diet for six weeks. The rats' detrusor muscle was isolated for pharmacological and histopathological examinations.

RESULTS:

In the control and study groups, mean body weights were 431.5 ± 27.6 g and 528.0 ± 36.2 g, respectively (p < 0.001). Electrical stimulation of the detrusor strips of the control group resulted in gradual contraction. A decreased contractile response was shown in the study group. Acetylcholine in 10-7-10-3 molar concentration produced a decreased contractile response in the study group, compared to the control group (p < 0.01). The study group showed marked subepithelial and intermuscular fibrosis in the bladder.

CONCLUSION:

Carbohydrate-rich diet causes marked subepithelial and extracellular fibrosis and changes in contractility in the detrusor within a six-week period. Changes have higher costs in therapeutic choices and correction of these changes remains difficult. Putting an end to carbohydrate-rich diet would seem to be more cost-effective than dealing with the effects of consuming it in high proportions which should be the national policy worldwide.

 

High and low sodium intakes are associated with incident chronic kidney disease in patients with normal renal function and hypertension.

Yoon CY, Noh J, Lee J, Kee YK, Seo C, Lee M, Cha MU, Kim H, Park S, Yun HR, Jung SY, Jhee JH, Han SH, Yoo TH, Kang SW, Park JT.

Kidney Int. 2017 Nov 29. pii: S0085-2538(17)30764-0. doi: 10.1016/j.kint.2017.09.016. [Epub ahead of print]

PMID: 29198468

Abstract

The association between salt intake and renal outcome in subjects with preserved kidney function remains unclear. Here we evaluated the effect of sodium intake on the development of chronic kidney disease (CKD) in a prospective cohort of people with normal renal function. Data were obtained from the Korean Genome and Epidemiology Study, a prospective community-based cohort study while sodium intake was estimated by a 24-hour dietary recall Food Frequency Questionnaire. A total of 3,106 individuals with and 4,871 patients without hypertension were analyzed with a primary end point of CKD development [a composite of estimated glomerular filtration rate (eGFR) under 60 mL/min/1.73 m2 and/or development of proteinuria during follow-up]. The median ages were 55 and 47 years, the proportions of males 50.9% and 46.3%, and the median eGFR 92 and 96 mL/min/1.73 m2 in individuals with and without hypertension, respectively. During a median follow-up of 123 months in individuals with hypertension and 140 months in those without hypertension, CKD developed in 27.8% and 16.5%, respectively. After adjusting for confounders, multiple Cox models indicated that the risk of CKD development was significantly higher in people with hypertension who consumed less than 2.08 g/day or over 4.03 g/day sodium than in those who consumed between 2.93-4.03 g/day sodium. However, there was no significant difference in the incident CKD risk among each quartile of people without hypertension. Thus, both high and low sodium intakes were associated with increased risk for CKD, but this relationship was only observed in people with hypertension.

KEYWORDS:

chronic kidney disease; dietary sodium; hypertension

 

Resveratrol inhibits obesity-associated adipose tissue dysfunction and tumor growth in a mouse model of postmenopausal claudin-low breast cancer.

Rossi EL, Khatib SA, Doerstling SS, Bowers LW, Pruski M, Ford NA, Glickman RD, Niu M, Yang P, Cui Z, DiGiovanni J, Hursting SD.

Mol Carcinog. 2017 Nov 20. doi: 10.1002/mc.22763. [Epub ahead of print]

PMID: 29197120

Abstract

Adipose tissue dysregulation, a hallmark of obesity, contributes to a chronic state of low-grade inflammation and is associated with increased risk and progression of several breast cancer subtypes, including claudin-low breast tumors. Unfortunately, mechanistic targets for breaking the links between obesity-associated adipose tissue dysfunction, inflammation, and claudin-low breast cancer growth have not been elucidated. Ovariectomized female C57BL/6 mice were randomized (n = 15/group) to receive a control diet, a diet-induced obesity (DIO) diet, or a DIO + resveratrol (0.5% wt/wt) diet. Mice consumed these diets ad libitum throughout study and after 6 weeks were orthotopically injected with M-Wnt murine mammary tumor cells, a model of estrogen receptor (ER)-negative claudin-low breast cancer. Compared with controls, DIO mice displayed adipose dysregulation and metabolic perturbations including increased mammary adipocyte size, cyclooxygenase-2 (COX-2) expression, inflammatory eicosanoid levels, macrophage infiltration, and prevalence of crown-like structures (CLS). DIO mice (relative to controls) also had increased systemic inflammatory cytokines and decreased adipocyte expression of peroxisome proliferator-activated receptor gamma (PPARγ) and other adipogenesis-regulating genes. Supplementing the DIO diet with resveratrol prevented obesity-associated increases in mammary tumor growth, mammary adipocyte hypertrophy, COX-2 expression, macrophage infiltration, CLS prevalence, and serum cytokines. Resveratrol also offset the obesity-associated downregulation of adipocyte PPARγ and other adipogenesis genes in DIO mice. Our findings suggest that resveratrol may inhibit obesity-associated inflammation and claudin-low breast cancer growth by inhibiting adipocyte hypertrophy and associated adipose tissue dysregulation that typically accompanies obesity.

KEYWORDS:

diet-induced obesity; mammary tumor; resveratrol

 

[The below paper is pdf-availed.]

Changes in body mass index and mid-upper arm circumference in relation to all-cause mortality in older adults.

Schaap LA, Quirke T, Wijnhoven HAH, Visser M.

Clin Nutr. 2017 Nov 15. pii: S0261-5614(17)31402-4. doi: 10.1016/j.clnu.2017.11.004. [Epub ahead of print]

PMID: 29195733

Abstract

BACKGROUND & AIMS:

The assessment of weight loss as an indicator of poor nutritional status in older persons is currently widely applied to establish risk of mortality. Little is known about the relationship between changes in mid-upper arm circumference (MUAC) and mortality in older individuals. The aim of the present study was to examine the association between 3-year change in MUAC and 20-year mortality in community-dwelling older adults and compare this to the association between body mass index (BMI) change and mortality.

METHODS:

Data on changes in MUAC (cm) and BMI (kg/m2), covariates, and mortality were available for 1307 Dutch older adults (49.7% men) aged 65 years and older in 1995/96 (mean 75.6 years, SD 6.5) from Longitudinal Aging Study Amsterdam (LASA). Anthropometric measurements were performed in 1992/93 with repeated measurements in 1995/96 (baseline), and a mortality follow up until July 2015. BMI and MUAC change were divided into quintiles, with the quintile including zero defined as the reference category. Cox regression analyses were performed to examine the associations of 3-year changes in MUAC and BMI with subsequent 20-year all-cause mortality, adjusted for demographic and health factors. Age, sex and initial measurement of BMI and MUAC (1992/93) were tested for effect modification (P = <0.10).

RESULTS:

Mean baseline BMI was 26.7 kg/m2 (SD 4.2) with a 3-year change of -0.2 (SD 1.5). Mean baseline MUAC was 30.5 cm (SD 3.5) with a 3-year change of -0.8 (SD 1.6). Age, sex, and BMI and MUAC 3 years prior were effect modifiers in the associations between change in anthropometric measurement and mortality. Decrease in MUAC was not associated with mortality in persons with a higher initial MUAC (≥31 cm), while for persons with a lower initial MUAC, a decrease in MUAC of ≤-2.15 was associated with increased mortality risk (HR 1.54; 95% CI: 1.14-2.09), also when further stratified on median age and sex. In stratified analysis of BMI change for median initial BMI (26.5) and additionally stratified for median age and sex, the associations between a BMI decrease of ≤-1.19 and mortality fluctuated, mostly statistically not significant. No associations were found for gain in MUAC or BMI.

CONCLUSIONS:

Given that MUAC loss is more strongly and consistently associated with an increased mortality risk in older individuals with a low initial MUAC compared to BMI loss, this may be a more recommendable measure to use in clinical practice for assessing poor nutritional status, instead of weight loss.

KEYWORDS:

Body mass index; Mid-upper arm circumference; Mortality; Nutritional status; Undernutrition; Weight loss

 

Disease burden and costs from excess alcohol consumption, obesity, and viral hepatitis: fourth report of the Lancet Standing Commission on Liver Disease in the UK.

Williams R, Alexander G, Armstrong I, Baker A, Bhala N, Camps-Walsh G, Cramp ME, de Lusignan S, Day N, Dhawan A, Dillon J, Drummond C, Dyson J, Foster G, Gilmore I, Hudson M, Kelly D, Langford A, McDougall N, Meier P, Moriarty K, Newsome P, O'Grady J, Pryke R, Rolfe L, Rice P, Rutter H, Sheron N, Taylor A, Thompson J, Thorburn D, Verne J, Wass J, Yeoman A.

Lancet. 2017 Nov 28. pii: S0140-6736(17)32866-0. doi: 10.1016/S0140-6736(17)32866-0. [Epub ahead of print] Review.

PMID: 29198562

Abstract

This report contains new and follow-up metric data relating to the eight main recommendations of the Lancet Standing Commission on Liver Disease in the UK, which aim to reduce the unacceptable harmful consequences of excess alcohol consumption, obesity, and viral hepatitis. For alcohol, we provide data on alcohol dependence, damage to families, and the documented increase in alcohol consumption since removal of the above-inflation alcohol duty escalator. Alcoholic liver disease will shortly overtake ischaemic heart disease with regard to years of working life lost. The rising prevalence of overweight and obesity, affecting more than 60% of adults in the UK, is leading to an increasing liver disease burden. Favourable responses by industry to the UK Government's soft drinks industry levy have been seen, but the government cannot continue to ignore the number of adults being affected by diabetes, hypertension, and liver disease. New direct-acting antiviral drugs for the treatment of chronic hepatitis C virus infection have reduced mortality and the number of patients requiring liver transplantation, but more screening campaigns are needed for identification of infected people in high-risk migrant communities, prisons, and addiction centres. Provision of care continues to be worst in regions with the greatest socioeconomic deprivation, and deficiencies exist in training programmes in hepatology for specialist registrars. Firm guidance is needed for primary care on the use of liver blood tests in detection of early disease and the need for specialist referral. This report also brings together all the evidence on costs to the National Health Service and wider society, in addition to the loss of tax revenue, with alcohol misuse in England and Wales costing £21 billion a year (possibly up to £52 billion) and obesity costing £27 billion a year (treasury estimates are as high as £46 billion). Voluntary restraints by the food and drinks industry have had little effect on disease burden, and concerted regulatory and fiscal action by the UK Government is essential if the scale of the medical problem, with an estimated 63 000 preventable deaths over the next 5 years, is to be addressed.

 

Changes in older people's care profiles during the last 2 years of life, 1996-1998 and 2011-2013: a retrospective nationwide study in Finland.

Aaltonen M, Forma L, Pulkki J, Raitanen J, Rissanen P, Jylha M.

BMJ Open. 2017 Dec 1;7(11):e015130. doi: 10.1136/bmjopen-2016-015130.

PMID: 29196476

Abstract

OBJECTIVES:

The time of death is increasingly postponed to a very high age. How this change affects the use of care services at the population level is unknown. This study analyses the care profiles of older people during their last 2 years of life, and investigates how these profiles differ for the study years 1996-1998 and 2011-2013.

DESIGN:

Retrospective cross-sectional nationwide data drawn from the Care Register for Health Care, the Care Register for Social Care and the Causes of Death Register. The data included the use of hospital and long-term care services during the last 2 years of life for all those who died in 1998 and in 2013 at the age of ≥70 years in Finland.

METHODS:

We constructed four care profiles using two criteria: (1) number of days in round-the-clock care (vs at home) in the last 2 years of life and (2) care transitions during the last 6 months of life (ie, end-of-life care transitions).

RESULTS:

Between the study periods, the average age at death and the number of diagnoses increased. Most older people (1998: 64.3%, 2013: 59.3%) lived at home until their last months of life (profile 2) after which they moved into hospital or long-term care facilities. This profile became less common and the profiles with a high use of care services became more common (profiles 3 and 4 together in 1998: 25.0%, in 2013: 30.9%). People with dementia, women and the oldest old were over-represented in the latter profiles. In both study periods, fewer than one in ten stayed at home for the whole last 6 months (profile 1).

CONCLUSIONS:

Postponement of death to a very old age may translate into more severe disability in the last months or years of life. Care systems must be prepared for longer periods of long-term care services needed at the end of life.

KEYWORDS:

ageing; care profile; care services; dementia; long-term care; pattern of care

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Time-Restricted Feeding Alters the Innate Immune Response to Bacterial Endotoxin.

Cissé YM, Borniger JC, Lemanski E, Walker WH 2nd, Nelson RJ.

J Immunol. 2017 Dec 4. pii: ji1701136. doi: 10.4049/jimmunol.1701136. [Epub ahead of print]

PMID: 29203514

Abstract

An important entraining signal for the endogenous circadian clock, independent of light, is food intake. The circadian and immune systems are linked; forced desynchrony of the circadian clock via nighttime light exposure or genetic ablation of core clock components impairs immune function. The timing of food intake affects various aspects of the circadian clock, but its effects on immune function are unknown. We tested the hypothesis that temporal desynchrony of food intake alters innate immune responses. Adult male Swiss Webster mice were provided with food during the night, the day, or ad libitum for 4 wk, followed by administration of LPS prior to the onset of either the active phase (zeitgeber time [ZT]12: Experiment 1) or the inactive phase (ZT0: Experiment 2). Three hours after LPS administration, blood was collected, and serum was tested for bacteria-killing capacity against Escherichia coli, as a functional assay of immune function. Additionally, cytokine expression was examined in the serum (protein), spleen, and hypothalamus (mRNA). Day-fed mice suppressed bacteria-killing capacity and serum cytokine responses to LPS during the active phase (ZT12). Night-fed mice increased bactericidal capacity, as well as serum and hypothalamic mRNA responses of certain proinflammatory cytokines during the active phase. Only day-fed mice enhanced serum cytokine responses when LPS challenge occurred during the inactive phase (ZT0); this did not result in enhanced bactericidal capacity. These data suggest that mistimed feeding has functional relevance for immune function and provide further evidence for the integration of the circadian, metabolic, and immune systems.

 

Confounding by ill health in the observed association between BMI and mortality: evidence from the HUNT Study using offspring BMI as an instrument.

Carslake D, Davey Smith G, Gunnell D, Davies N, Nilsen TIL, Romundstad P.

Int J Epidemiol. 2017 Dec 1. doi: 10.1093/ije/dyx246. [Epub ahead of print]

PMID: 29206928

https://academic.oup.com/ije/advance-article/doi/10.1093/ije/dyx246/4653787

https://watermark.silverchair.com/dyx246.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAbYwggGyBgkqhkiG9w0BBwagggGjMIIBnwIBADCCAZgGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMP7-9BVm03hvP0eI_AgEQgIIBadFFko01LJc78kyixaYDW_pfREguiqh1K82tByfSB0H2z84JdjWpIk3J3xzgEa7tP-H96_3g4lBd0b_Umu4ptTC42xWhipYPKU0ezdIYZolW0IHhv29Qww9aIllv8UMbLv_huK9r8NEY2vvP1-KhIx13T2OlZ7IiOdaFn4VIZCYLfWKDx5tp-NiJaz-95y_B0yipaxVbXRbL2MWTJJ2YkPOY-YOGwY-ZNNb9KD6tsTwc2vGwT9KykN_Up2xn7Hq1nNJjhS82mZ5MrekQPyk4J2_JkJo4OSTm4pkNIvHBcra2cr0XkMn7p4VC0vhT1_He-jU6Zz5BBerMOLf-WxKPtPGBti0LfwSjvfapolLcXt365TV6Km3TY76hy48Nl09gLuAJVmoN_Aj30p-7P7c7mQXACSUMQ8gSCDZIkLRUFn2Ip8HCq10sYH5_ZyVQwnEUmUIWnn0dfx9Q-Gar7D0IGjcPi11Shfsl_C8

Abstract

BACKGROUND:

The observational association between mortality and body mass index (BMI) is U-shaped, leading to highly publicized suggestions that moderate overweight is beneficial to health. However, it is unclear whether elevated mortality is caused by low BMI or if the association is confounded, for example by concurrent ill health.

METHODS:

Using HUNT, a Norwegian prospective study, 32 452 mother-offspring and 27 747 father-offspring pairs were followed up to 2009. Conventional hazard ratios for parental mortality per standard deviation of BMI were estimated using Cox regression adjusted for behavioural and socioeconomic factors. To estimate hazard ratios with reduced susceptibility to confounding, particularly from concurrent ill health, the BMI of parents' offspring was used as an instrumental variable for parents' own BMI. The shape of mortality-BMI associations was assessed using cubic splines.

RESULTS:

There were 18 365 parental deaths during follow-up. Conventional associations of mortality from all-causes, cardiovascular disease and cancer with parents' own BMI were substantially nonlinear, with elevated mortality at both extremes and minima at 21-25 kg m-2. Equivalent associations with offspring BMI were positive and there was no evidence of elevated parental mortality at low offspring BMI. The linear instrumental variable hazard ratio for all-cause mortality per standard deviation increase in BMI was 1.18 (95% confidence interval: 1.10, 1.26), compared with 1.05 (1.03, 1.06) in the conventional analysis.

CONCLUSIONS:

Elevated mortality rates at high BMI appear causal, whereas excess mortality at low BMI is likely exaggerated by confounding by factors including concurrent ill health. Conventional studies probably underestimate the adverse population health consequences of overweight.

KEYWORDS:

Body mass index; cohort study; confounding; instrumental variables; mortality; reverse causation

 

Walnut consumption in a weight reduction intervention: effects on body weight, biological measures, blood pressure and satiety.

Rock CL, Flatt SW, Barkai HS, Pakiz B, Heath DD.

Nutr J. 2017 Dec 4;16(1):76. doi: 10.1186/s12937-017-0304-z.

PMID: 29202751 Free Article

Abstract

BACKGROUND:

Dietary strategies that help patients adhere to a weight reduction diet may increase the likelihood of weight loss maintenance and improved long-term health outcomes. Regular nut consumption has been associated with better weight management and less adiposity. The objective of this study was to compare the effects of a walnut-enriched reduced-energy diet to a standard reduced-energy-density diet on weight, cardiovascular disease risk factors, and satiety.

METHODS:

Overweight and obese men and women (n = 100) were randomly assigned to a standard reduced-energy-density diet or a walnut-enriched (15% of energy) reduced-energy diet in the context of a behavioral weight loss intervention. Measurements were obtained at baseline and 3- and 6-month clinic visits. Participants rated hunger, fullness and anticipated prospective consumption at 3 time points during the intervention. Body measurements, blood pressure, physical activity, lipids, tocopherols and fatty acids were analyzed using repeated measures mixed models.

RESULTS:

Both study groups reduced body weight, body mass index and waist circumference (time effect p < 0.001 for each). Change in weight was -9.4 (0.9)% vs. -8.9 (0.7)% (mean [sE]), for the standard vs. walnut-enriched diet groups, respectively. Systolic blood pressure decreased in both groups at 3 months, but only the walnut-enriched diet group maintained a lower systolic blood pressure at 6 months. The walnut-enriched diet group, but not the standard reduced-energy-density diet group, reduced total cholesterol and low-density lipoprotein cholesterol (LDL-C) at 6 months, from 203 to 194 mg/dL and 121 to 112 mg/dL, respectively (p < 0.05). Self-reported satiety was similar in the groups.

CONCLUSIONS:

These findings provide further evidence that a walnut-enriched reduced-energy diet can promote weight loss that is comparable to a standard reduced-energy-density diet in the context of a behavioral weight loss intervention. Although weight loss in response to both dietary strategies was associated with improvements in cardiovascular disease risk factors, the walnut-enriched diet promoted more favorable effects on LDL-C and systolic blood pressure.

TRIAL REGISTRATION:

KEYWORDS:

Blood pressure; Cardiovascular disease risk factors; Nuts; Satiety; Weight loss

 

Effect of a vitamin and mineral supplementation on glycemic status: Results from a community-based program.

Kimball SM, Emery JCH, Lewanczuk RZ.

J Clin Transl Endocrinol. 2017 Nov 7;10:28-35. doi: 10.1016/j.jcte.2017.11.002. eCollection 2017 Dec.

PMID: 29204369 Free Article

http://www.jctejournal.com/article/S2214-6237(17)30075-3/fulltext

http://www.jctejournal.com/article/S2214-6237(17)30075-3/pdf

Abstract

AIMS:

Diet is a major risk factor for type 2 diabetes mellitus. As cofactors necessary for enzyme function of all metabolic pathways, vitamins and minerals have the potential to improve glucose metabolism. We investigated the effects of a nutrient intervention program on glycemic status.

METHODS:

We used a form of natural experiment to compare Pure North program participants (n = 1018) that received vitamin D alone (Vital 1) or vitamin D in combination with other nutrients (Vital 2) during two different time periods. Changes in 25-hydroxyvitamin D [25(OH)D], high-sensitivity C reactive protein (hs-CRP), glycated hemoglobin (HbA1c) and glycemic status were characterized over one and two years.

RESULTS:

Serum 25(OH)D concentrations increased significantly in both Vital 1 (to 111  ±  49 nmol/L) and Vital 2 (to 119  ±  52 nmol/L) over one year. HbA1c and hs-CRP were significantly reduced over time in Vital 2. Higher 25(OH)D levels after one year were associated with larger decreases in HbA1c and hs-CRP in Vital 2. At one year, 8% of Vital 2 and 16% of Vital 1 participants progressed from normoglycemia to prediabetes/diabetes, whereas 44% of Vital 2 and 8% of Vital prediabetes/diabetes subjects regressed to normoglycemia.

CONCLUSIONS:

Vitamin D combined with other nutrients was associated with a reduced risk of progression to diabetes and with an increased rate of reversion to normoglycemia in high risk participants. The results suggest that nutrient supplementation regimes may provide a safe, economical and effective means for lowering diabetes risk. Further examination of this potential via randomized controlled trials is warranted.

KEYWORDS:

Multivitamin; Normoglycemia; Nutritional supplements; Prediabetes; Type 2 diabetes mellitus; Vitamin D

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Achieved systolic blood pressure in older people: a systematic review and meta-analysis.

Moraes AAI, Baena CP, Muka T, Bano A, Buitrago-Lopez A, Zazula A, Erbano BO, Schio NA, Guedes MH, Bramer WM, Franco OH, Faria-Neto JR.

BMC Geriatr. 2017 Dec 5;17(1):279. doi: 10.1186/s12877-017-0672-4.

PMID: 29207946

Abstract

BACKGROUND:

It remains unclear into which level the systolic blood pressure (SBP) should be lowered in order to provide the best cardiovascular protection among older people. Hypertension guidelines recommendation on attaining SBP levels <150 mmHg in this population is currently based on experts' opinion. To clarify this issue, we systematically reviewed and quantified available evidence on the impact of achieving different SBP levels <150 mmHg on various adverse outcomes in subjects aged ≥60 years old receiving antihypertensive drug treatment.

METHODS:

We searched 8 databases to identify randomized controlled trials (RCTs) and post-hoc analyses or subanalyses of RCTs reporting the effects of attaining different SBP levels <150 mmHg on the risk of stroke, acute myocardial infarction, heart failure, cardiovascular mortality and all-cause mortality in participants aged ≥60 years. We performed random-effects meta-analyses stratified by study design.

RESULTS:

Eleven studies (> 33,600 participants) were included. Compared with attaining SBP levels ≥140 mmHg, levels of 130 to <140 mmHg were not associated with lower risk of outcomes in the meta-analysis of RCTs, whereas there was an associated reduction of cardiovascular mortality (RR 0.72, 95% CI 0.59-0.88) and all-cause mortality (RR 0.86, 95% CI 0.75-0.99) in the meta-analysis of post-hoc analyses or subanalyses of RCTs. Limited and conflicting data were available for the SBP levels of <130 mmHg and 140 to <150 mmHg.

CONCLUSIONS:

Among older people, there is suggestive evidence that achieving SBP levels of 130 to <140 mmHg is associated with lower risks of cardiovascular and all-cause mortality. Future trials are required to confirm these findings and to provide additional evidence regarding the <130 and 140 to <150 mmHg SBP levels.

KEYWORDS:

Aged; Antihypertensive agents; Antihypertensive drugs; Antihypertensives; Blood pressure; Hypertension; Older people

 

Dietary n-3 polyunsaturated fatty acids, fish consumption, and endometrial cancer risk: a meta-analysis of epidemiological studies.

Hou R, Yao SS, Liu J, Wang LL, Wu L, Jiang L.

Oncotarget. 2017 May 30;8(53):91684-91693. doi: 10.18632/oncotarget.18295. eCollection 2017 Oct 31.

PMID: 29207677

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=18295&path%5B%5D=58664

Abstract

The relationship between intake of fish and n-3 fatty acids and endometrial cancer risk has not been consistent across epidemiological studies. We quantitatively assessed the aforementioned association through a systematic review and meta-analysis. PubMed and Embase were searched through March 2017 for eligible epidemiological studies. Fixed or random-effects models were used to pool relative risks (RRs) and 95% confidence intervals (CIs). The dose-response relationship was also evaluated. Based on the literature search, five prospective studies and 11 case-control studies were identified. All 16 studies were categorized as high-quality studies. After pooling available risk estimates, no significant association was detected between overall fish intake and endometrial cancer risk. In subgroup analyses, every one additional serving/week of fish intake was significantly associated with inversed endometrial cancer risk in studies adjusted for smoking (RR (95% CI): 0.95 (0.91-1.00)), or studies performed in Europe (RR (95% CI): 0.90 (0.84-0.97)), but not in other tested subgroups. In studies conducted in Asia, there was significant positive association (RR (95% CI): 1.15 (1.10-1.21)). Regarding n-3 PUFA intake, marginally inverse associations of high EPA or DHA intake were detected (EPA: RR (95% CI) = 0.79 (0.61-1.04); DHA: RR (95% CI) = 0.85 (0.64-1.11)). Dose-response analyses suggested a significant nonlinear relationship between DHA intake and endometrial cancer risk (p: 0.04). Overall, this meta-analysis suggests that intake of n-3 PUFA may be inversely associated with endometrial cancer risk at some level of evidence, although the exact relationship, especially for fish intake, needs further characterization. Further well-designed studies are warranted.

KEYWORDS:

endometrial cancer; epidemiology; fish; n-3 fatty acids

 

 

High dietary intake of aromatic amino acids increases risk of hypertension.

Teymoori F, Asghari G, Mirmiran P, Azizi F.

J Am Soc Hypertens. 2017 Nov 24. pii: S1933-1711(17)30407-2. doi: 10.1016/j.jash.2017.11.004. [Epub ahead of print]

PMID: 29208471

Abstract

Recent studies investigated the relation between amino acids and blood pressure. Our aim was to examine the association between intake of aromatic amino acids (AAAs) and risk of hypertension. A total of 4288 individuals, aged 20-70 years, participants of the Tehran Lipid and Glucose Study, who were free of hypertension at baseline (2008-2011), were followed for 3 years (2011-2014). Average intakes of AAAs including phenylalanine, tyrosine, and tryptophan were collected using a valid and reliable food frequency questionnaire at baseline. Adjusted logistic regression models were used to report odds ratio (OR) of hypertension across quartiles of AAAs. At the end of follow-up, 429 (10%) hypertension cases were ascertained. The adjusted OR of hypertension for percentage of AAAs from total protein intakes was 1.63 (95% confidence interval, 1.06-2.50; P for trend: .03) when comparing the highest quartile to the lowest. Furthermore, in the adjusted analyses, a statistically significant positive relationship was observed between the highest versus the lowest quartile intake of phenylalanine (OR = 1.66; 95% confidence interval, 1.14-2.47; P for trend: .03). However, there was no significant association of tyrosine and tryptophan intakes with hypertension risk. Our data suggest that AAAs may increase the risk of incident hypertension.

KEYWORDS:

Hypertension; phenylalanine; tryptophan; tyrosine

 

Food groups and risk of colorectal cancer.

Schwingshackl L, Schwedhelm C, Hoffmann G, Knüppel S, Preterre AL, Iqbal K, Bechthold A, De Henauw S, Michels N, Devleesschauwer B, Boeing H, Schlesinger S.

Int J Cancer. 2017 Dec 6. doi: 10.1002/ijc.31198. [Epub ahead of print]

PMID: 29210053

Abstract

The aim of this systematic review and meta-analysis was to summarize the evidence on the relation between intake of 12 major food groups, including whole grains, refined grains, vegetables, fruit, nuts, legumes, eggs, dairy, fish, red meat, processed meat, and sugar-sweetened beverages with risk of colorectal cancer (CRC). We conducted a systematic search in PubMed and Embase for prospective studies investigating the association between these 12 food groups and risk of CRC until April 2017. Summary risk ratios (RRs) and 95% confidence intervals (95% CI) were estimated using a random effects model for high vs. low intake categories, as well as for linear and non-linear relationships. An inverse association was observed for whole grains (RR30g/d : 0.95, 95% CI 0.93, 0.97; n=9 studies), vegetables (RR100g/d : 0.97, 95% CI 0.96, 0.98; n=15), fruit (RR100g/d : 0.97, 95% CI 0.95, 0.99; n=16), and dairy (RR200g/d : 0.93, 95% CI 0.91, 0.94; n=15), while a positive association for red meat (RR100g/d : 1.12, 95% CI 1.06, 1.19; n=21) and processed meat (RR50g/d : 1.17, 95% CI 1.10, 1.23; n=16), was seen in the linear dose-response meta-analysis. Some evidence for non-linear relationships was observed between vegetables, fruit, and dairy and risk of colorectal cancer. Findings of this meta-analysis showed that a diet characterized by high intake of whole grains, vegetables, fruit, and dairy products and low amounts of red meat and processed meat was associated with lower risk of CRC.

KEYWORDS:

colorectal cancer; diet; dose-response; food groups; meta-analysis

 

Effect of resveratrol and pterostilbene on aging and longevity.

Li YR, Li S, Lin CC.

Biofactors. 2017 Dec 6. doi: 10.1002/biof.1400. [Epub ahead of print] Review.

PMID: 29210129

Abstract

Over the past years, several studies have found that foods rich in polyphenols protect against age-related disease, such as atherosclerosis, cardiovascular disease, cancer, arthritis, cataracts, osteoporosis, type 2 diabetes (T2D), hypertension and Alzheimer's disease. Resveratrol and pterostilbene, the polyphenol found in grape and blueberries, have beneficial effects as anti-aging compounds through modulating the hallmarks of aging, including oxidative damage, inflammation, telomere attrition and cell senescence. In this review, we discuss the relationship between resveratrol and pterostilbene and possible aging biomarker, including oxidative stress, inflammation, and high-calorie diets. Moreover, we also discuss the positive effect of resveratrol and pterostilbene on lifespan, aged-related disease, and health maintenance. Furthermore, we summarize a variety of important mechanisms modulated by resveratrol and pterostilbene possibly involved in attenuating age-associated disorders. Overall, we describe resveratrol and pterostilbene potential for prevention or treatment of several age-related diseases by modulating age-related mechanisms.

 

Dietary Intake of Protein from Different Sources and Weight Regain, Changes in Body Composition and Cardiometabolic Risk Factors after Weight Loss: The DIOGenes Study.

van Baak MA, Larsen TM, Jebb SA, Martinez A, Saris WHM, Handjieva-Darlenska T, Kafatos A, Pfeiffer AFH, Kunešová M, Astrup A.

Nutrients. 2017 Dec 6;9(12). pii: E1326. doi: 10.3390/nu9121326.

PMID: 29211027

http://www.mdpi.com/2072-6643/9/12/1326/htm

Abstract

An increase in dietary protein intake has been shown to improve weight loss maintenance in the DIOGenes trial. Here, we analysed whether the source of the dietary proteins influenced changes in body weight, body composition, and cardiometabolic risk factors during the weight maintenance period while following an energy-restricted diet. 489 overweight or obese participants of the DIOGenes trial from eight European countries were included. They successfully lost >8% of body weight and subsequently completed a six month weight maintenance period, in which they consumed an ad libitum diet varying in protein content and glycemic index. Dietary intake was estimated from three-day food diaries. A higher plant protein intake with a proportional decrease in animal protein intake did not affect body weight maintenance or cardiometabolic risk factors. A higher plant protein intake from non-cereal products instead of cereal products was associated with benefits for body weight maintenance and blood pressure. Substituting meat protein for protein from other animal sources increased insulin and HOMA-IR (homeostasis model assessment of insulin resistance). This analysis suggests that not only the amount of dietary proteins, but also the source may be important for weight and cardiometabolic risk management. However, randomized trials are needed to test the causality of these associations.

KEYWORDS:

animal protein; cardiometabolic risk factors; cereal protein; diet; meat protein; obesity; plant protein; protein sources; weight loss maintenance

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Mortality in persons with undetected and diagnosed hypertension, type 2 diabetes, and hypothyroidism, compared with persons without corresponding disease - a prospective cohort study; The HUNT Study, Norway.

Jørgensen P, Langhammer A, Krokstad S, Forsmo S.

BMC Fam Pract. 2017 Dec 7;18(1):98. doi: 10.1186/s12875-017-0672-7.

PMID: 29212453

https://bmcfampract.biomedcentral.com/articles/10.1186/s12875-017-0672-7

https://bmcfampract.biomedcentral.com/track/pdf/10.1186/s12875-017-0672-7?site=bmcfampract.biomedcentral.com

Abstract

BACKGROUND:

Suggested strategies in reducing the impact of non-communicable diseases (NCD) are early diagnosing and screening. We have limited proof of benefit of population screening for NCD. Increased mortality in persons with diagnosed NCD has been shown for decades. However, mortality in undetected NCD has barely been studied. This paper explores whether all-cause mortality differed between persons with diagnosed hypothyroidism, type 2 diabetes (T2DM), and hypertension, compared with persons with undetected-, and with persons without the corresponding disease.

METHODS:

A prospective cohort study of the general population in Nord-Trøndelag, Norway. Persons ≥20 years at baseline 1995-97 were followed until death or June 15, 2016. Cox proportional hazards models were used to compute age and multiple adjusted hazard ratios (HR) with 95% confidence intervals (CI) for the association between disease status and all-cause mortality. The number of participants in the hypothyroidism study was 31,960, in the T2DM study 37,957, and in the hypertension study 63,371.

RESULTS:

Mortality was increased in persons with diagnosed type 2 diabetes and hypertension, compared to persons without corresponding disease; HR 1.69 (95% CI 1.55-1.84) and HR 1.23 (95% CI 1.09-1.39), respectively. Among persons with undetected T2DM, the HR was 1.21 (95% CI 1.08-1.37), whilst among undetected hypothyroidism and hypertension, mortality was not increased compared with persons without the diseases. Further, the association with mortality was stronger in persons with long duration of T2DM (HR 1.96 (95% CI 1.57-2.44)) and hypertension (HR 1.32 (95% CI 1.17-1.49)), compared with persons with short duration (HR 1.29 (1.09-1.53) and HR 1.16 (1.03-1-30) respectively).

CONCLUSIONS:

Mortality was increased in persons with diagnosed T2DM and hypertension, and in undetected T2DM, compared with persons without the diseases. The strength of the association with mortality in undetected T2DM was however lower compared with persons with diagnosed T2DM, and mortality was not increased in persons with undetected hypothyroidism and hypertension, compared with persons without the diseases. Thus, future research needs to test more thoroughly if early diagnosing of these diseases, such as general population screening, is beneficial for health.

KEYWORDS:

Chronic disease; Diabetes; Hypertension; Primary care; Public health; Thyroid disorders

 

Meeting Sleep Guidelines Is Associated With Better Health-Related Quality of Life and Reduced Premature All-Cause Mortality Risk.

Loprinzi PD, Joyner C.

Am J Health Promot. 2017 Jan 1:890117116687459. doi: 10.1177/0890117116687459. [Epub ahead of print]

PMID: 29214822

Abstract

PURPOSE:

To examine whether meeting sleep guidelines (7-9 hours/night) is associated with better health-related quality of life (HRQOL) and reduced all-cause mortality risk.

DESIGN:

Prospective cohort study.

SETTING:

2005 to 2010 National Health and Nutrition Examination Survey.

PARTICIPANTS:

A total of 13 423 adults.

MEASURES:

Sleep duration and HRQOL were assessed from self-report; covariates assessed via survey, examination, and laboratory data; and mortality assessed through 2011 via matching from the National Death Index.

ANALYSIS:

Cox proportional hazard regression and ordinal logistic regression.

RESULTS:

After adjusting for age, gender, race-ethnicity, body mass index, education, smoking, white blood cell level, iron level, red blood cell distribution width, mean platelet volume, blood pressure, diabetes, coronary artery disease, physical activity, and depression, those meeting sleep guidelines had an 19% reduced risk of premature all-cause mortality (hazard ratio = 0.81; 95% confidence interval [CI]: 0.67-0.99; P = .04). After adjustments, those meeting sleep guidelines had better HRQOL (β = -0.30; 95% CI: -0.38 to -0.21; P < .001). Results for the ordinal regression and Cox proportional analyses were similar in unadjusted and minimally adjusted models.

CONCLUSION:

Obtaining optimal levels of sleep is associated with better HRQOL and reduced premature mortality risk, independent of demographic, behavioral, and biological conditions. These findings underscore the importance of achieving optimal levels of sleep.

KEYWORDS:

epidemiology; quality of life; sleep; survival

 

Prognostic effect of body mass index to mortality in Korean older persons.

Kim H, Yoon JL, Lee A, Jung Y, Kim MY, Cho JJ, Ju YS.

Geriatr Gerontol Int. 2017 Dec 7. doi: 10.1111/ggi.13213. [Epub ahead of print]

PMID: 29214747

Abstract

AIM:

Body mass index (BMI) is regarded as a predictor of life expectancy and a determinant of mortality. However, the effect of age on BMI-related mortality remains unclear. The aim of the present study was to examine the prognostic effect of BMI to mortality risk among Korean older persons.

METHODS:

Data were collected from the Korean National Health Insurance Services' Senior Cohort database. This study analyzed the data of 79 341 men and 91 298 women aged ≥65 years who underwent health examinations in the 2007 fiscal year. Individual mortality was identified 5 years after 2008. The participants were stratified into seven groups according to basal BMI. Hazard ratios of death were calculated through Cox proportional hazards model after adjusting for age, sex, smoking status, exercise, alcohol intake and income.

RESULTS:

During the 5-year follow up, 11 651 men and 7 235 women died. In both sexes, a lower BMI had a higher hazard ratio (HR), but the trend of increasing HR at high BMI was not clear. For men, the lowest HR was 0.79 (95% CI 0.71-0.87) at a BMI of 27.5-30.0 kg/m2 . For women, the lowest HR was 0.84 (95% CI 0.78-0.91) at a BMI of 25.0-27.5 kg/m2 . For both sexes, the relative mortality risk was associated with a lower BMI.

CONCLUSIONS:

A high BMI is not associated with increased mortality in older adults aged ≥65 years, whereas a lower BMI is associated with an increased mortality risk in later life in this population.

KEYWORDS:

body mass index; elderly; mortality; obesity

 

Dietary Factors and Female Breast Cancer Risk: A Prospective Cohort Study.

Kim JH, Lee J, Jung SY, Kim J.

Nutrients. 2017 Dec 7;9(12). pii: E1331. doi: 10.3390/nu9121331.

PMID: 29215604

http://www.mdpi.com/2072-6643/9/12/1331/htm

Abstract

Breast cancer is the leading cause of cancer in females and has become a major global health priority. This prospective cohort study investigated the association of dietary factors, including food items and dietary habits, with the risk of breast cancer in Korean women. Study participants were women aged 30 years or older, recruited from the National Cancer Center in South Korea between August 2002 and May 2007. They were followed until December 2014 using the Korea Central Cancer Registry to identify breast cancer cases. Among 5046 non-pre-diagnosed cancer participants, 72 breast cancer cases were prospectively identified. Participants with breast cancer had a significantly higher educational level (college or higher: 58.3% vs. 39.5%, p = 0.01), were more likely to have ever smoked (22.2% vs. 7.8%, p < 0.001), and were more likely to have a history of benign breast tumors (10% vs. 4%, p = 0.02) than non-cases. Consumption of grilled meat conferred a significantly higher risk of breast cancer in all women (hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.09-2.85) and in postmenopausal women (HR 3.06, 95% CI 1.31-7.15). High-cholesterol food intake was associated with a higher risk in all women (HR 1.69, 95% CI 1.01-2.82). Irregular meal intake was associated with an elevated risk in all women (HR 2.19, 95% CI 1.20-3.98, p for trend = 0.01) and in premenopausal women (HR 2.35, 95% CI 1.13-4.91, p for trend = 0.03). Our findings suggest that grilled meat and high-cholesterol food intake and irregular eating habits may be associated with a higher risk of breast cancer. Further studies with longer follow-up periods that include information on portion size, hormone receptor status, carcinogen levels in grilled meat, and a classification of foods by source are required.

KEYWORDS:

Korean; breast cancer; dietary factors; dietary habits; food groups; prospective cohort study

 

A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: A randomized controlled trial (HELFIMED).

Parletta N, Zarnowiecki D, Cho J, Wilson A, Bogomolova S, Villani A, Itsiopoulos C, Niyonsenga T, Blunden S, Meyer B, Segal L, Baune BT, O'Dea K.

Nutr Neurosci. 2017 Dec 7:1-14. doi: 10.1080/1028415X.2017.1411320. [Epub ahead of print]

PMID: 29215971

http://www.tandfonline.com/doi/full/10.1080/1028415X.2017.1411320

http://www.tandfonline.com/doi/pdf/10.1080/1028415X.2017.1411320?needAccess=true

Abstract

OBJECTIVES:

We investigated whether a Mediterranean-style diet (MedDiet) supplemented with fish oil can improve mental health in adults suffering depression.

METHODS:

Adults with self-reported depression were randomized to receive fortnightly food hampers and MedDiet cooking workshops for 3 months and fish oil supplements for 6 months, or attend social groups fortnightly for 3 months. Assessments at baseline, 3 and 6 months included mental health, quality of life (QoL) and dietary questionnaires, and blood samples for erythrocyte fatty acid analysis.

RESULTS:

n = 152 eligible adults aged 18-65 were recruited (n = 95 completed 3-month and n = 85 completed 6-month assessments). At 3 months, the MedDiet group had a higher MedDiet score (t = 3.95, P < 0.01), consumed more vegetables (t = 3.95, P < 0.01), fruit (t = 2.10, P = 0.04), nuts (t = 2.29, P = 0.02), legumes (t = 2.41, P = 0.02) wholegrains (t = 2.63, P = 0.01), and vegetable diversity (t = 3.27, P < 0.01); less unhealthy snacks (t = -2.10, P = 0.04) and red meat/chicken (t = -2.13, P = 0.04). The MedDiet group had greater reduction in depression (t = -2.24, P = 0.03) and improved mental health QoL scores (t = 2.10, P = 0.04) at 3 months. Improved diet and mental health were sustained at 6 months. Reduced depression was correlated with an increased MedDiet score (r = -0.298, P = 0.01), nuts (r = -0.264, P = 0.01), and vegetable diversity (r = -0.303, P = 0.01). Other mental health improvements had similar correlations, most notably for increased vegetable diversity and legumes. There were some correlations between increased omega-3, decreased omega-6 and improved mental health.

DISCUSSION:

This is one of the first randomized controlled trials to show that healthy dietary changes are achievable and, supplemented with fish oil, can improve mental health in people with depression.

KEYWORDS:

Depression; Fish oil; Intervention; Mediterranean diet; Mental health; Omega-3; Omega-6; Quality of life

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Lonelier than ever? Loneliness of older people over two decades.

Dahlberg L, Agahi N, Lennartsson C.

Arch Gerontol Geriatr. 2017 Nov 16;75:96-103. doi: 10.1016/j.archger.2017.11.004. [Epub ahead of print]

PMID: 29220739

Abstract

To live with feelings of loneliness has negative implications for quality of life, health and survival. This study aimed to examine changes in loneliness among older people, both with regard to prevalence rates, and socio-demographic, social and health-related correlates of loneliness. This study had a repeated cross-sectional design and was based on the nationally representative Swedish Panel Study of Living Conditions of the Oldest Old (SWEOLD). Analyses of trends in loneliness covered the years 1992, 2002, 2004, 2011 and 2014, and included people aged 77 years or older (n=2 572). Analyses of correlates of loneliness covered 2004 and 2014, and included people aged 70 years or older (n=1 962). Logistic regression analyses were conducted with findings presented as average marginal effects. Contrary to what is often assumed, there has been no increase in loneliness among older people over time (1992-2014). Regression analyses for 2004 and 2014 showed that social and health-related correlates were more strongly associated with loneliness than socio-demographic correlates. Psychological distress was most strongly associated with loneliness, followed by widowhood. Most associations between the correlates and loneliness were stable over time.

KEYWORDS:

Loneliness; Predictor; Risk factor; Sweden; Trend

 

Contemporary Hormonal Contraception and the Risk of Breast Cancer

Lina S. Mørch, Ph.D., Charlotte W. Skovlund, M.Sc., Philip C. Hannaford, M.D., Lisa Iversen, Ph.D., Shona Fielding, Ph.D., and Øjvind Lidegaard, D.M.Sci.

N Engl J Med 2017; 377:2228-2239December 7, 2017DOI: 10.1056/NEJMoa1700732

Abstract

BACKGROUND

Little is known about whether contemporary hormonal contraception is associated with an increased risk of breast cancer.

METHODS

We assessed associations between the use of hormonal contraception and the risk of invasive breast cancer in a nationwide prospective cohort study involving all women in Denmark between 15 and 49 years of age who had not had cancer or venous thromboembolism and who had not received treatment for infertility. Nationwide registries provided individually updated information about the use of hormonal contraception, breast-cancer diagnoses, and potential confounders.

RESULTS

Among 1.8 million women who were followed on average for 10.9 years (a total of 19.6 million person-years), 11,517 cases of breast cancer occurred. As compared with women who had never used hormonal contraception, the relative risk of breast cancer among all current and recent users of hormonal contraception was 1.20 (95% confidence interval [CI], 1.14 to 1.26). This risk increased from 1.09 (95% CI, 0.96 to 1.23) with less than 1 year of use to 1.38 (95% CI, 1.26 to 1.51) with more than 10 years of use (P=0.002). After discontinuation of hormonal contraception, the risk of breast cancer was still higher among the women who had used hormonal contraceptives for 5 years or more than among women who had not used hormonal contraceptives. Risk estimates associated with current or recent use of various oral combination (estrogen–progestin) contraceptives varied between 1.0 and 1.6. Women who currently or recently used the progestin-only intrauterine system also had a higher risk of breast cancer than women who had never used hormonal contraceptives (relative risk, 1.21; 95% CI, 1.11 to 1.33). The overall absolute increase in breast cancers diagnosed among current and recent users of any hormonal contraceptive was 13 (95% CI, 10 to 16) per 100,000 person-years, or approximately 1 extra breast cancer for every 7690 women using hormonal contraception for 1 year.

CONCLUSIONS

The risk of breast cancer was higher among women who currently or recently used contemporary hormonal contraceptives than among women who had never used hormonal contraceptives, and this risk increased with longer durations of use; however, absolute increases in risk were small.

>>>>>>>>>>>>>>>>>>>

Oral Contraceptives and the Small Increased Risk of Breast Cancer.

Hunter DJ.

N Engl J Med. 2017 Dec 7;377(23):2276-2277. doi: 10.1056/NEJMe1709636. No abstract available.

PMID: 29211666

In this issue of the Journal, Mørch et al.1 present the results of a large prospective study of the association between the use of hormonal contraceptives and the risk of breast cancer among women in Denmark who were younger than 50 years of age. They observed a 20% higher risk among women who were currently using or had recently used hormonal contraceptives than among those who had never used them, and the risk increased with a longer duration of use.

The association between the current use of oral contraceptives and breast cancer is well established; the relative risk of 1.20 in the current analysis is similar to that reported by the Collaborative Group on Hormonal Factors in Breast Cancer2 and in previous prospective studies such as the Nurses’ Health Studies.3,4 The advantage of the analysis by Mørch et al. is that most of the formulations used were those that have been prevalent in Denmark since 1995; the Collaborative Group data were based on the use of formulations in the 1980s and earlier. The study by Mørch and colleagues confirms that the increased breast-cancer risk of approximately 20% among women who were currently using oral contraceptives, a risk that was initially reported with the use of older, often higher-dose formulations, also applies to contemporary formulations of oral contraceptives.

In an apparent contrast, the results of a Centers for Disease Control and Prevention (CDC) case–control study reported by Marchbanks et al. in the Journal in 2002 showed no significant increase in the risk of breast cancer5; however, owing to the age range of the women involved in that study (35 to 64 years), almost all use of oral contraceptives was among women who had used them in the past, and the upper bound of the 95% confidence interval for current use of 1.3 in the CDC study comfortably includes the relative risk of 1.20 in the present study. In 2007, the International Agency for Research on Cancer concluded that there was sufficient evidence to establish the carcinogenicity of combined oral estrogen–progestin contraceptives in humans, with an increased risk of breast cancer limited to women who were currently using or had recently used them.6 In the current study, there was a suggestion that risk may persist more than 5 years after discontinuation of hormonal contraception among women who had used hormonal contraceptives for at least 5 years, but this should be regarded as preliminary; the increase in risk would not have been significant with adjustment for multiple comparisons involving different categories of duration and time since last use.

Thus, the main result of the study is expected. The much larger sample size than in previous studies permits the examination of subgroups for which previous prospective assessments have been limited. A clear duration–response association was observed, supporting the credibility of the findings. The association was also significant among women younger than 35 years of age and among nulliparous women.

The most important subgroup analyses in the current study involved the risks associated with the various formulations used, particularly various progestins. Although there are some differences in the relative risks, all the confidence intervals overlap the consensus estimate of 1.20. Thus, these results do not suggest that any particular preparation is free of risk. Notably, the associations between the levonorgestrel-only oral formulation and the levonorgestrel-releasing intrauterine device (IUD) and breast-cancer risk were unequivocally positive.

What, then, are the implications? First, the approximately 20% higher risk of breast cancer among women who currently use hormonal contraceptives and those who do not must be placed in the context of the low incidence rates of breast cancer among younger women. As the authors show, owing to the risk of breast cancer that is more than 5 times as high among women in their 40s as among women in their 30s, the excess number of cases of breast cancer associated with the use of hormonal contraceptives increases rapidly with age. The absolute increase in risk is 13 per 100,000 women overall, but only 2 per 100,000 women younger than 35 years of age; most of the cases that occurred in this analysis occurred among women who were using oral contraceptives in their 40s.

Second, the risk of breast cancer needs to be balanced against the benefits of the use of oral contraceptives. Beyond the fact that they provide an effective means of contraception and may benefit women with dysmenorrhea or menorrhagia, the use of oral contraceptives is associated with substantial reductions in the risks of ovarian, endometrial, and colorectal cancers later in life. Indeed, some calculations have suggested that the net effect of the use of oral contraceptives for 5 years or longer is a slight reduction in the total risk of cancer.7 The higher excess risk as women move into their 40s — of breast cancer as well as of other uncommon risks such as myocardial infarction and stroke — suggests careful consideration of alternative methods of contraception such as nonhormonal, long-acting, reversible contraceptives (e.g., IUDs) in this age group.

Third, these data suggest that the search for an oral contraceptive that does not elevate the risk of breast cancer needs to continue. In the 1980s and 1990s, there was some optimism regarding the development of a formulation that would reduce a woman’s risk of breast cancer,8 but research into this possibility appears to have stalled.

Finally, this study exemplifies the opportunities to use population-wide “big data” approaches to evaluate very important issues at a low cost. Investigators in countries that have universal access to health care and those who have community agreement for the linkage of various databases are better able to conduct research that clarifies both the risks and benefits of common exposures, including prescription medicines.

>>>>>>>>>>>>>>>>>>>>>>>>>

Contemporary Hormonal Contraception and the Risk of Breast Cancer.

Mørch LS, Skovlund CW, Hannaford PC, Iversen L, Fielding S, Lidegaard Ø.

N Engl J Med. 2017 Dec 7;377(23):2228-2239. doi: 10.1056/NEJMoa1700732.

PMID: 29211679

Abstract

BACKGROUND:

Little is known about whether contemporary hormonal contraception is associated with an increased risk of breast cancer.

METHODS:

We assessed associations between the use of hormonal contraception and the risk of invasive breast cancer in a nationwide prospective cohort study involving all women in Denmark between 15 and 49 years of age who had not had cancer or venous thromboembolism and who had not received treatment for infertility. Nationwide registries provided individually updated information about the use of hormonal contraception, breast-cancer diagnoses, and potential confounders.

RESULTS:

Among 1.8 million women who were followed on average for 10.9 years (a total of 19.6 million person-years), 11,517 cases of breast cancer occurred. As compared with women who had never used hormonal contraception, the relative risk of breast cancer among all current and recent users of hormonal contraception was 1.20 (95% confidence interval [CI], 1.14 to 1.26). This risk increased from 1.09 (95% CI, 0.96 to 1.23) with less than 1 year of use to 1.38 (95% CI, 1.26 to 1.51) with more than 10 years of use (P=0.002). After discontinuation of hormonal contraception, the risk of breast cancer was still higher among the women who had used hormonal contraceptives for 5 years or more than among women who had not used hormonal contraceptives. Risk estimates associated with current or recent use of various oral combination (estrogen-progestin) contraceptives varied between 1.0 and 1.6. Women who currently or recently used the progestin-only intrauterine system also had a higher risk of breast cancer than women who had never used hormonal contraceptives (relative risk, 1.21; 95% CI, 1.11 to 1.33). The overall absolute increase in breast cancers diagnosed among current and recent users of any hormonal contraceptive was 13 (95% CI, 10 to 16) per 100,000 person-years, or approximately 1 extra breast cancer for every 7690 women using hormonal contraception for 1 year.

CONCLUSIONS:

The risk of breast cancer was higher among women who currently or recently used contemporary hormonal contraceptives than among women who had never used hormonal contraceptives, and this risk increased with longer durations of use; however, absolute increases in risk were small.

 

To help save the heart, is it time to retire cholesterol tests?

BY MITCH LESLIE

SCIENCE08 DEC 2017 : 1237-1238

Measuring a blood protein, apoB, might save more lives.

To help save the heart, is it time to retire cholesterol tests?

Summary

Doctors typically gauge our risk of developing heart disease from our levels of low-density lipoprotein (LDL) cholesterol or non–high density lipoprotein cholesterol. But some researchers argue that the blood protein apolipoprotein B (apoB) is a more accurate indicator because it captures the number of cholesterol-carrying particles that cause atherosclerosis. ApoB backers point to recent analyses that found high apoB levels better predicted patients' likelihood of suffering a heart attack or stroke and a genetic study that showed that reducing apoB had a bigger effect on cardiovascular risk than did reducing LDL cholesterol. However, many researchers remain convinced that switching to measuring apoB would not provide enough benefit to outweigh the disruption to clinical procedures that would result.

The next time you go in for a medical checkup, your doctor will probably make a mistake that could endanger your life, contends cardiologist Allan Sniderman of McGill University in Montreal, Canada. Most physicians order what he considers the wrong test to gauge heart disease risk: a standard cholesterol readout, which may indicate levels of low-density lipoprotein (LDL) or non-high density lipoprotein (non-HDL) cholesterol. What they should request instead, Sniderman argues, is an inexpensive assay for a blood protein known as apolipoprotein B (apoB).

ApoB indicates the number of cholesterol-laden particles circulating in the blood—a truer indicator of the threat to our arteries than absolute cholesterol levels, some researchers believe. Sniderman asserts that routine apoB tests, which he says cost as little as $20, would identify millions more patients who could benefit from cholesterol-cutting therapies and would spare many others from unnecessary treatment. “If I can diagnose [heart disease] more accurately using apoB, and if I can treat more effectively using apoB, it's worth 20 bucks,” he says.

Sniderman and a cadre of other scientists have been stumping for apoB for years, but recent reanalyses of clinical data, together with genetic studies, have boosted their confidence. At last month's American Heart Association (AHA) meeting in Anaheim, California, for example, Sniderman presented a new take on the National Health and Nutrition Examination Survey (NHANES), a famous census of the U.S. population's health. The reexamination, which compared people with different apoB levels but the same non-HDL cholesterol readings, crystallizes the importance of measuring the protein, he says. Across the United States, patients who have the highest apoB readings will suffer nearly 3 million more heart attacks, strokes, and other cardiovascular events in the next 15 years than will people with the lowest levels, Sniderman reported. As lipidologist Daniel Rader of the University of Pennsylvania Perelman School of Medicine puts it, the question of whether LDL cholesterol is the best measure of cardiovascular risk no has a clear answer: “No.”

But plenty of scientists disagree. “Many lines of evidence say there's not a lot more predictive power of apoB over LDL cholesterol,” says cholesterol researcher Scott Grundy of the University of Texas Southwestern Medical Center in Dallas, who has helped craft several sets of cardiology care guidelines. And changing clinical practice would be disruptive. Standard heart disease risk guidelines downplay or omit apoB, and the algorithms that help doctors decide which patients to treat don't incorporate it.

ApoB backers have a new opportunity to make their case. A committee of researchers and doctors is reworking the most influential U.S. recommendations for cholesterol treatment, published by the American College of Cardiology (ACC) and AHA, and should issue an update next year. The European equivalents are also being revamped, although a new version won't be ready for 2 to 3 years, says cardiologist and genetic epidemiologist Brian Ference of the University of Cambridge in the United Kingdom, who is taking part in the rewrite.

Nobody expects these latest revisions to jilt cholesterol for apoB, but its advocates say there's increasing science on their side. Cholesterol cruises through our blood in several kinds of protein-containing particles, including HDLs, LDLs, and very low-density lipoproteins (VLDLs). When certain particles, such as LDLs and VLDLs, depart the bloodstream and get stuck in the lining of our arteries, atherosclerosis can result. Total cholesterol level was the first widely used indicator of this risk, but after researchers discovered that one form of cholesterol, HDL, may be protective, LDL cholesterol became the benchmark. Now, some physicians favor non-HDL cholesterol, which encompasses multiple cholesterol types, including LDL and VLDL.

All of these measures, however, reveal the amount of lipid in the blood, rather than the number of cholesterol-hauling particles. ApoB, in contrast, provides a direct measure of their abundance because each LDL or VLDL particle contains a single copy of the protein.

Still, even apoB advocates admit that LDL cholesterol's track record is pretty good. About 85% of the time, it provides an accurate indication of a patient's likelihood of developing cardiovascular disease, Ference says. But that means it's wrong 15% of the time, he adds.

A 2009 study found that nearly half of patients admitted to hospitals because of heart attacks had normal or low LDL levels. So by measuring LDL alone, doctors risk overlooking people who need treatment or, if they are already taking drugs to trim their cholesterol levels, a more intensive regimen.

At the same time, some people taking drugs for what seem to be dangerously high LDL cholesterol levels may not need treatment, Sniderman says. A more discriminating test for cardiovascular risk could spare these people from potential side effects and save money. Although cholesterol-lowering statins are cheap, Sniderman notes that newer drugs given when statins aren't enough, such as the PCSK9 inhibitors, can cost tens of thousands of dollars per year.

Switching to measuring apoB would improve diagnoses because it better reflects the mechanism of cardiovascular disease, according to Sniderman. “The data support that it's the LDL particles themselves that are the bad actors,” rather than the cholesterol they contain, Rader says. The more of these particles that course through a patient's blood, the more get stuck in the arterial walls and the higher the probability of cardiovascular disease. Because LDL cholesterol and apoB are intertwined, both measures give the same result for many patients. However, the amount of cholesterol a particle contains can vary. So LDL cholesterol levels can be misleading for patients who have few large particles or many small ones.

No current drugs drive down just apoB, making its impact difficult to untangle from the effect of lowering cholesterol overall. But in a 2015 paper, Sniderman and colleagues reanalyzed data from the famous Framingham Heart Study, which has been probing the causes of cardiovascular disease for nearly 70 years. The patients with the best odds of surviving for at least 20 years had low levels of apoB and non-HDL cholesterol, the team found. But the patients with the worst chances had high levels of apoB, even though their non-HDL cholesterol was low. Similarly, the reassessment of the NHANES data that Sniderman presented at the AHA meeting suggests that apoB is a better predictor of risk.

In this illustration of a low-density lipoprotein particle, apolipoprotein B (blue) is surrounded by various forms of cholesterol (orange and yellow) and other lipids.

ILLUSTRATION: JUAN GAERTNER/SCIENCE SOURCE

Also pointing to apoB's importance is a type of analysis in which researchers comb through genetic data from large numbers of patients to identify gene variants that influence a particular trait. Scientists then track the variants' sway on health, a method called Mendelian randomization because it relies on accidents of heredity to create comparison groups. “It's essentially nature's randomized trial,” Ference says. In a study in The Journal of the American Medical Association in September, he and his colleagues dissected the impact of variants of two genes involved in cholesterol metabolism: CETP and HMGCR.

Using data from more than 100,000 patients, the researchers found that people with sluggish versions of the enzyme encoded by CETP showed equivalent reductions in apoB and LDL cholesterol levels and were less likely than people with vigorous versions of the enzyme to suffer cardiovascular crises such as heart attacks or strokes. But the scientists saw a telling difference when they analyzed patients who also produced underactive versions of HMGCR's enzyme. Although these people showed further decreases in LDL cholesterol, their apoB levels—and their cardiovascular risk—didn't decline by as much. That discrepancy suggests that reducing apoB has a bigger protective effect than lowering LDL, Ference says.

The picture is clear, says preventive cardiologist Seth Martin of Johns Hopkins University School of Medicine in Baltimore, Maryland. “The totality of evidence is in favor of apoB being an important marker that can identify risk even when LDL is controlled.”

But would the gains be worth the disruption? “The poor frontline primary care doctor doesn't want to have to think about apoB and non-HDL cholesterol,” says preventive cardiologist and epidemiologist Jennifer Robinson of the University of Iowa in Iowa City, who was vice chair of the committee that drafted the most recent ACC/AHA recommendations in 2013. “It's too much information—and when you give people too much information they ignore it.”

Cardiologist Robert Eckel of the University of Colorado School of Medicine in Aurora, who was also on the ACC/AHA committee, agrees. “I don't see apoB changing the playing field very much,” he says.

Many apoB advocates reluctantly concur. LDL cholesterol is deeply entrenched in medical routines, and “it's not going to change any time soon,” Rader says. “I go from depression to worse depression,” Sniderman says.

But if future guidelines start to emphasize apoB's diagnostic value and drug companies begin to target it, Ference thinks physicians will eventually pay heed to the protein. “The argument is that LDL cholesterol is good enough,” he says. “But as we move toward more personalized medicine, it's not.”

 

[The below paper is pdf-availed.]

Metabolic markers as cancer clues.

Mayers JR.

Science. 2017 Dec 8;358(6368):1265. doi: 10.1126/science.aar2001. No abstract available.

PMID: 29217564

Changes in branched-chain amino acids may be first sign of certain cancers

The study of cancer metabolism began almost a century ago when Otto Warburg noted that cancerous tissues metabolize glucose differently from their normal counterparts (1). It has since become widely understood that cancer cells, and proliferating cells more broadly, carry out a metabolic program that favors the accumulation of new biomass components by synthesizing amino acids, lipids, and nucleotides necessary for the generation of daughter cells (2).

Contemporary studies have focused on cell-autonomous metabolic alterations in cancer, using cell culture models to dissect the contributions of different oncogenes and tumor suppressors to observed metabolic phenotypes (3). These systems have yielded numerous promising therapeutic targets (4), although their nonphysiologic nature raises the question of how broadly findings may apply to patients (3). In fact, models deviating from standard culture conditions have uncovered previously underappreciated metabolic flexibility within cancer cells (2), and growing the same cell line either in culture or in animals alters the fuel these cells use (5).

Searching for Cancer's Signal

Based on these findings, we posited that evaluating metabolism in mouse models of cancer and in human subjects might better identify metabolic weaknesses in cancer cells that could be exploited therapeutically. Specifically, we sought to determine how cancer can influence whole-body metabolism through interactions with normal cells and the tissue microenvironment, particularly in early-stage disease.

Initially, we focused on pancreatic cancer, a leading and increasingly common cause of cancer death in the United States (6). Pancreatic cancer is disproportionally associated with systemic metabolic alterations such as insulin resistance (7) and cachexia, a condition characterized by wasting of muscle and fat, which is commonly seen in endstage disease (8). Although these phenotypes are well documented, it was unknown whether more subtle metabolic changes, such as alterations in circulating nutrient levels, could yield insight into earlier time points of disease development.

A Metabolic Indicator of Early Pancreatic Cancer Emerges

We used mass-spectrometry metabolomics to analyze samples from four prospective human cohorts and found an association between elevated plasma levels of branched-chain amino acids (BCAAs) and future diagnosis of pancreatic cancer (9). Intriguingly, this association was strongest 2 to 5 years before diagnosis, a period hypothesized to overlap with occult disease (10). Thus, although these cohort studies are traditionally used to identify risk factors for future disease development, our findings indicated that BCAA elevations might instead represent a marker of early pancreatic cancer.

We recapitulated these observations in two mouse models of pancreatic cancer driven by mutations in Kras and Trp53 and confirmed our hypothesis from the human data that the changes occurred during the earliest histologic stages of invasive disease. Using stable isotope-based labeling, we demonstrated that elevated plasma BCAAs resulted from increased systemic protein turnover, most likely due to protein degradation in the muscle. This suggested that the process of tissue breakdown that is associated with cachexia during end-stage disease likely begins years earlier in humans than previously thought (9).

In this study, we used a reverse-translational approach, taking human data into mouse models, which allowed us to dramatically shift how we study prospective human cohorts and to exploit the variable lengths of time from blood draw to cancer diagnosis to study early disease. As a result, we were able to understand a mechanism of early disease progression and not just predictors of disease development and diagnosis.

Circulating Indicators of Altered Metabolism are also Present in Lung Cancer

After demonstrating that one type of cancer could drive whole-body metabolic alterations, we wondered whether these effects might occur across other cancer types. To allow for a direct comparison, we chose to investigate plasma metabolite alterations in another Kras- and Trp53-driven model of cancer: non-small-cell lung carcinoma (NSCLC).

In contrast to our observations in the isogenic pancreatic cancer model, plasma levels of BCAAs were decreased in NSCLC tumor-bearing mice (11). Using stable-isotope BCAA tracers, we observed that NSCLC cells, but not pancreatic cancer cells, take up more free BCAAs compared with their respective tissues of origin.

NSCLC cells incorporate plasma BCAAs into proteins and additionally use them as a source of nitrogen for de novo synthesis of nonessential amino acids and nucleotides (11). This activity drives the decreased plasma BCAA levels observed in this model (see the figure). Pancreatic cancer cells, on the other hand, rely more on the uptake and metabolism of material from the surrounding stromal environment to obtain amino acids (11–13). These distinct phenotypes were reflected in expression levels of BCAA metabolic enzymes in both human and mouse NSCLC. Deletion of the enzymes responsible for nitrogen extraction blocked formation of NSCLC, but not pancreatic tumors, in mice despite having no effect on proliferation of either cell type in culture (11). This study revealed an in vivo, NSCLC-specific metabolic vulnerability.

Branched-chain amino acids and cancer

Early pancreatic cancer and non-small-cell lung carcinoma (NSCLC) are associated with distinct changes in plasma branched-chain amino acids (BCAAs). In pancreatic cancer, increased protein turnover and muscle breakdown with concurrent low utilization by tumor cells drive increased levels of BCAAs. In contrast, NSCLC cells take up more free BCAAs, resulting in decreased concentrations.

GRAPHIC: ADAPTED BY A. KITTERMAN/SCIENCE

Beyond Genetics: Tissue of Origin and Tumor Environment Matter, Too

In the clinic, both the selection of patients for some treatments and the development of new therapies relies heavily on the underlying genetic profile of a particular tumor (14). Implicit in this approach is the hypothesis that specific mutations produce predictable phenotypes that can be targeted by a single method in a variety of cancer types. This hypothesis has also been applied to metabolism, where stereotyped driver mutation-metabolic phenotype relationships based largely on in vitro studies have been described (15–17). Our findings, however, suggest that tissue of origin and tumor environment, in addition to genetics, are important factors that influence metabolic weaknesses for a given tumor. Consistent with this idea, administration of chemotherapies that target nucleotide metabolism has historically been based on tumor type rather than genetics (18).

Using mouse and human data, we have explored metabolic interactions between nascent tumors and their host environment, both local and distant, which measurably influence whole-body metabolism. Exploring the mechanisms driving these changes has altered our interpretation of prospective human cohort data, opening new avenues of investigation into early disease. Additionally, our work on the combined influence of mutational status and tissue context on a tumor's metabolic preferences resulted in our identification of a previously unappreciated, cancer-type-specific metabolic vulnerability that could be targeted therapeutically.

Our work expands the promise of precision-medicine approaches to targeting cancer metabolism. Continued investigation with in vivo systems remains our best hope, both to understand the metabolic features of early cancer development and to develop strategies to exploit these features therapeutically.

 

Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study.

Caudill MA, Strupp BJ, Muscalu L, Nevins JEH, Canfield RL.

FASEB J. 2017 Dec 7. pii: fj.201700692RR. doi: 10.1096/fj.201700692RR. [Epub ahead of print]

PMID: 29217669

Abstract

Rodent studies demonstrate that supplementing the maternal diet with choline during pregnancy produces life-long cognitive benefits for the offspring. In contrast, the two experimental studies examining cognitive effects of maternal choline supplementation in humans produced inconsistent results, perhaps because of poor participant adherence and/or uncontrolled variation in intake of choline or other nutrients. We examined the effects of maternal choline supplementation during pregnancy on infant cognition, with intake of choline and other nutrients tightly controlled. Women entering their third trimester were randomized to consume, until delivery, either 480 mg choline/d (n = 13) or 930 mg choline/d (n = 13). Infant information processing speed and visuospatial memory were tested at 4, 7, 10, and 13 mo of age (n = 24). Mean reaction time (RT) averaged across the four ages was significantly faster for infants born to mothers in the 930 (vs. 480) mg choline/d group. This result indicates that maternal consumption of approximately twice the recommended amount of choline during the last trimester improves infant information processing speed. Furthermore, for the 480-mg choline/d group, there was a significant linear effect of exposure duration (infants exposed longer showed faster RTs), suggesting that even modest increases in maternal choline intake during pregnancy may produce cognitive benefits for offspring.-Caudill, M. A., Strupp, B. J., Muscalu, L., Nevins, J. E. H., Canfield, R. L. Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study.

KEYWORDS:

longitudinal; reaction time; saccade; visuospatial memory

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Predictors of long-term care among nonagenarians: the Vitality 90 + Study with linked data of the care registers.

Kauppi M, Raitanen J, Stenholm S, Aaltonen M, Enroth L, Jylhä M.

Aging Clin Exp Res. 2017 Dec 8. doi: 10.1007/s40520-017-0869-6. [Epub ahead of print]

PMID: 29222731

Abstract

BACKGROUND:

The need for long-term care services increases with age. However, little is known about the predictors of long-term care (LTC) entry among the oldest old.

AIMS:

Aim of this study was to assess predictors of LTC entry in a sample of men and women aged 90 years and older.

METHODS:

This study was based on the Vitality 90 + Study, a population-based study of nonagenarians in the city of Tampere, Finland. Baseline information about health, functioning and living conditions were collected by mailed questionnaires. Information about LTC was drawn from care registers during the follow-up period extending up to 11 years. Cox regression models were used for the analyses, taking into account the competing risk of mortality.

RESULTS:

During the mean follow-up period of 2.3 years, 844 (43%) subjects entered first time into LTC. Female gender (HR 1.39, 95% CI 1.14-1.69), having at least two chronic conditions (HR 1.24, 95% CI 1.07-1.44), living alone (HR 1.37, 95% CI 1.15-1.63) and help received sometimes (HR 1.23, 95% CI 1.02-1.49) or daily (HR 1.68, 95% CI 1.38-2.04) were independent predictors of LTC entry.

CONCLUSION:

Risk of entering into LTC was increased among women, subjects with at least two chronic conditions, those living alone and with higher level of received help. Since number of nonagenarians will increase and the need of care thereby, it is essential to understand predictors of LTC entry to offer appropriate care for the oldest old in future.

KEYWORDS:

Health services use; Long-term care; Longitudinal methods; Population aging

 

The Geriatric Nutritional Risk Index predicts mortality in nonagenarians and centenarians receiving home care.

Wang H, Hai S, Zhou Y, Liu P, Dong BR.

Asia Pac J Clin Nutr. 2018;27(1):78-83. doi: 10.6133/apjcn.022017.10.

PMID: 29222883

https://pdfs.semanticscholar.org/dcc6/3b99b8368c1f1e902cac1438decb89f3b984.pdf

Abstract

BACKGROUND AND OBJECTIVES:

The increasing prevalence of malnutrition in old people is related to the risk of illness and death. A number of screening tools to detect malnutrition have been used in the elderly to assess nutritional status and predict prognosis. The aim of the present study was to investigate the ability of the Geriatric Nutritional Risk Index (GNRI) to assess nutritional status and predict mortality in very old home-care people by using a cross-sectional study of Chinese older people aged 90-105 years.

METHODS AND STUDY DESIGN:

The present study was based on a 4-year follow-up of mortality data from a previous cross-sectional study. The study was conducted with a very elderly population with a mean age of 93.5±3.2 years (n=716; 230 men and 486 women). In 2005, trained researchers performed face-to-face interviews and physical and geriatric assessments to obtain information on sociodemographic factors, self-reported medical diseases, geriatric-specific conditions, anthropometric factors, biochemical data, and the GNRI score. In 2009, vital status were requested from the local government.

RESULTS:

After 4 years of follow-up, 371 participants died (125 men and 246 women, 51.8%). The median follow-up time was significantly worse in the nutritional risk group (GNRI <=98) (30.26±15.80 vs 42.27±11.82 months, p<0.001). Activities of daily living (ADL) impairment (hazard ratio {HR}=1.414, 95% CI=1.121-1.783), and GNRI score (HR=0.92, 95% CI=0.908-0.932) were associated with all-cause mortality according to a Cox regression analysis.

CONCLUSIONS:

The GNRI, a nutrition-related risk index, can predict mortality in very old Chinese home-care people.

 

Sex and ethnic/racial-specific risk factors for gallbladder disease.

Figueiredo JC, Haiman C, Porcel J, Buxbaum J, Stram D, Tambe N, Cozen W, Wilkens L, Le Marchand L, Setiawan VW.

BMC Gastroenterol. 2017 Dec 8;17(1):153. doi: 10.1186/s12876-017-0678-6.

PMID: 29221432

https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-017-0678-6

https://bmcgastroenterol.biomedcentral.com/track/pdf/10.1186/s12876-017-0678-6?site=bmcgastroenterol.biomedcentral.com

Abstract

BACKGROUND:

Gallbladder disease (GBD) is a highly prevalent condition; however, little is known about potential differences in risk factors by sex and ethnicity/race. Our aim was to evaluate dietary, reproductive and obesity-related factors and GBD in multiethnic populations.

METHODS:

We performed a prospective analysis from the Multiethnic Cohort study who self-identified as non-Hispanic White (n = 32,103), African American (n = 30,209), Japanese (n = 35,987), Native Hawaiian (n = 6942) and Latino (n = 39,168). GBD cases were identified using Medicare and California hospital discharge files (1993-2012) and self-completed questionnaires. We used exposure information on the baseline questionnaire to identify exposures of interest. Associations were estimated by hazard ratios and 95% confidence intervals using Cox models adjusted for confounders.

RESULT:

After a median 10.7 years of follow-up, there were 13,437 GBD cases. BMI over 25 kg/m2, diabetes, past and current smoking, red meat consumption, saturated fat and cholesterol were significant risk factors across ethnic/racial populations (p-trends < 0.01). Protective factors included vigorous physical activity, alcohol use, fruits, vegetables and foods rich in dietary fiber (p-trends < 0.01). Carbohydrates were inversely associated with GBD risk only among women and Latinos born in South America/Mexico (p-trend < 0.003). Parity was a significant risk factor among women; post-menopausal hormones use was only associated with an increased risk among White women (estrogen-only: HR = 1.24; 95% CI = 1.07-1.43 and estrogen + progesterone: HR = 1.23; 95% CI = 1.06-1.42).

CONCLUSION:

Overall, dietary, reproductive and obesity-related factors are strong risk factors for GBD affecting men and women of different ethnicities/races; however some risk factors appear stronger in women and certain ethnic groups.

KEYWORDS:

Cholecystectomy; Ethnicity/race; Gallbladder; Stones

 

Dietary supplementation with cysteine prevents adverse metabolic outcomes of repeated cures with paracetamol in old rats.

Mast C, Pourpe C, Voyard G, Rémond D, Migné C, Centeno D, Dardevet D, Savary-Auzeloux I, Papet I.

Br J Nutr. 2017 Dec;118(11):889-896. doi: 10.1017/S0007114517002847. Epub 2017 Nov 27.

PMID: 29173208

Abstract

Cysteine (Cys), a conditionally indispensable amino acid, is required for the detoxification of paracetamol (acetaminophen, N-acetyl-para-aminophenol, 4-hydroxy-acetanilide, APAP), a drug of widespread use in older persons. We recently reported that repeated APAP cures could worsen sarcopenia in old rats, likely to be due to the impairment of Cys/GSH homoeostasis. The aim of the study was to evaluate whether a dietary Cys supplementation during APAP cures could improve Cys/GSH homoeostasis and thus preserve skeletal muscle. Male 21·5-month-old Wistar rats received three 2-week-long cures of APAP (1 % of diet) alone or with extra Cys (0·5 % of diet), intercalated with washout periods of 2 weeks (APAP and APAP-Cys groups, respectively). They were compared with untreated control rats (CT group). CT and APAP-Cys groups were pair-fed to the APAP group. Dietary Cys supplementation was efficient to prevent increase in liver mass (P<0·0001), decrease in liver GSH (P<0·0001), increase in blood GSH concentration (P<0·0001), and to some extent, decrease in plasma free Cys concentration (P<0·05), all induced by repeated APAP cures. The addition of Cys to APAP cures decreased plasma alanine transaminase (P<0·05), the fractional synthesis rate of liver proteins (P<0·01), and increased masses of extensor digitorum longus (P<0·01), and soleus (P<0·05), compared with the APAP group. Cys supplementation prevented alteration in Cys/GSH homoeostasis and increased some muscle masses in old rats under repeated cures with a non-toxic dose of APAP.

KEYWORDS:

4-hydroxy-acetanilide); APAP paracetamol (acetaminophen; CT control; Cys cysteine; Cys–gly cysteinyl–glycine; Hcy homocysteine GM gastrocnemius; N-acetyl-para-aminophenol; Cysteine; GSH; Liver; Skeletal muscles

 

Substitutions between dairy product subgroups and risk of type 2 diabetes: the Danish Diet, Cancer and Health cohort.

Ibsen DB, Laursen ASD, Lauritzen L, Tjønneland A, Overvad K, Jakobsen MU.

Br J Nutr. 2017 Dec;118(11):989-997. doi: 10.1017/S0007114517002896. Epub 2017 Nov 27.

PMID: 29173212

Abstract

The aim of this study was to investigate the associations for specified substitutions between different subgroups of dairy products and the risk of type 2 diabetes. We used data from the Danish Diet, Cancer and Health cohort including 54 277 men and women aged 50-64 years at baseline. Information regarding intake of dairy products was obtained from a validated FFQ, and cases of type 2 diabetes were identified through the Danish National Diabetes Register. Cox proportional hazards regressions were used to estimate associations. During a median follow-up of 15·3 years, 7137 cases were identified. Low-fat yogurt products in place of whole-fat yogurt products were associated with a higher rate of type 2 diabetes (hazard ratio (HR) 1·17; 95 % CI 1·06, 1·29) per serving/d substituted. Whole-fat yogurt products in place of low-fat milk, whole-fat milk or buttermilk were associated with a lower rate of type 2 diabetes (HR 0·89; 95 % CI 0·83, 0·96; HR 0·89; 95 % CI 0·82, 0·96; HR 0·89; 95 % CI 0·81, 0·97; per serving/d substituted, respectively). The pattern of associations was similar when intake was expressed as kJ/d (kcal/d). These findings suggest that intake of whole-fat yogurt products in place of low-fat yogurt products, low-fat milk, whole-fat milk and buttermilk are associated with a lower rate of type 2 diabetes.

KEYWORDS:

HR hazard ratio; Cheese; Dairy products; Milk; Substitution studies; Yogurt

 

Wealth-Associated Disparities in Death and Disability in the United States and England.

Makaroun LK, Brown RT, Diaz-Ramirez LG, Ahalt C, Boscardin WJ, Lang-Brown S, Lee S.

JAMA Intern Med. 2017 Dec 1;177(12):1745-1753. doi: 10.1001/jamainternmed.2017.3903.

PMID: 29059279

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2659324

Abstract

IMPORTANCE:

Low income has been associated with poor health outcomes. Owing to retirement, wealth may be a better marker of financial resources among older adults.

OBJECTIVE:

To determine the association of wealth with mortality and disability among older adults in the United States and England.

DESIGN, SETTING, AND PARTICIPANTS:

The US Health and Retirement Study (HRS) and English Longitudinal Study of Aging (ELSA) are nationally representative cohorts of community-dwelling older adults. We examined 12 173 participants enrolled in HRS and 7599 enrolled in ELSA in 2002. Analyses were stratified by age (54-64 years vs 66-76 years) because many safety-net programs commence around age 65 years. Participants were followed until 2012 for mortality and disability.

EXPOSURES:

Wealth quintile, based on total net worth in 2002.

MAIN OUTCOMES AND MEASURES:

Mortality and disability, defined as difficulty performing an activity of daily living.

RESULTS:

A total of 6233 US respondents and 4325 English respondents aged 54 to 64 years (younger cohort) and 5940 US respondents and 3274 English respondents aged 66 to 76 years (older cohort) were analyzed for the mortality outcome. Slightly over half of respondents were women (HRS: 6570, 54%; ELSA: 3974, 52%). A higher proportion of respondents from HRS were nonwhite compared with ELSA in both the younger (14% vs 3%) and the older (13% vs 3%) age cohorts. We found increased risk of death and disability as wealth decreased. In the United States, participants aged 54 to 64 years in the lowest wealth quintile (Q1) (≤$39 000) had a 17% mortality risk and 48% disability risk over 10 years, whereas in the highest wealth quintile (Q5) (>$560 000) participants had a 5% mortality risk and 15% disability risk (mortality hazard ratio {HR}, 3.3; 95% CI, 2.0-5.6; P < .001; disability subhazard ratio [sHR], 4.0; 95% CI, 2.9-5.6; P < .001). In England, participants aged 54 to 64 years in Q1 (≤£34,000) had a 16% mortality risk and 42% disability risk over 10 years, whereas Q5 participants (>£310,550) had a 4% mortality risk and 17% disability risk (mortality HR, 4.4; 95% CI, 2.7-7.0; P < .001; disability sHR, 3.0; 95% CI, 2.1-4.2; P < .001). In 66- to 76-year-old participants, the absolute risks of mortality and disability were higher, but risk gradients across wealth quintiles were similar. When adjusted for sex, age, race, income, and education, HR for mortality and sHR for disability were attenuated but remained statistically significant.

CONCLUSIONS AND RELEVANCE:

Low wealth was associated with death and disability in both the United States and England. This relationship was apparent from age 54 years and continued into later life. Access to health care may not attenuate wealth-associated disparities in older adults.

 

Association of Warfarin Use With Lower Overall Cancer Incidence Among Patients Older Than 50 Years.

Haaland GS, Falk RS, Straume O, Lorens JB.

JAMA Intern Med. 2017 Dec 1;177(12):1774-1780. doi: 10.1001/jamainternmed.2017.5512.

PMID: 29114736

Abstract

IMPORTANCE:

In cancer models, warfarin inhibits AXL receptor tyrosine kinase-dependent tumorigenesis and enhances antitumor immune responses at doses not reaching anticoagulation levels. This study investigates the association between warfarin use and cancer incidence in a large, unselected population-based cohort.

OBJECTIVE:

To examine the association between warfarin use and cancer incidence.

DESIGN, SETTING, AND PARTICIPANTS:

This population-based cohort study with subgroup analysis used the Norwegian National Registry coupled with the Norwegian Prescription Database and the Cancer Registry of Norway. The cohort comprised all persons (N = 1 256 725) born between January 1, 1924, and December 31, 1954, who were residing in Norway from January 1, 2006, through December 31, 2012. The cohort was divided into 2 groups-warfarin users and nonusers; persons taking warfarin for atrial fibrillation or atrial flutter were the subgroup. Data were collected from January 1, 2004, to December 31, 2012. Data analysis was conducted from October 15, 2016, to January 31, 2017.

EXPOSURES:

Warfarin use was defined as taking at least 6 months of a prescription and at least 2 years from first prescription to any cancer diagnosis. If warfarin treatment started after January 1, 2006, each person contributed person-time in the nonuser group until the warfarin user criteria were fulfilled.

MAIN OUTCOMES AND MEASURES:

Cancer diagnosis of any type during the 7-year observation period (January 1, 2006, through December 31, 2012).

RESULTS:

Of the 1 256 725 persons in the cohort, 607 350 (48.3%) were male, 649 375 (51.7%) were female, 132 687 (10.6%) had cancer, 92 942 (7.4%) were classified as warfarin users, and 1 163 783 (92.6%) were classified as nonusers. Warfarin users were older, with a mean (SD) age of 70.2 (8.2) years, and were predominantly men (57 370 [61.7%]) as compared with nonusers, who had a mean (SD) age of 63.9 (8.6) years and were mostly women (613 803 [52.7%]). Among warfarin users and compared with nonusers, there was a significantly lower age- and sex-adjusted incidence rate ratio (IRR) in all cancer sites (IRR, 0.84; 95% CI, 0.82-0.86) and in prevalent organ-specific sites (lung, 0.80 [95% CI, 0.75-0.86]; prostate, 0.69 [95% CI, 0.65-0.72]; and breast, 0.90 [95% CI, 0.82-1.00]). There was no observed significant effect in colon cancer (IRR, 0.99; 95% CI, 0.93-1.06). In a subgroup analysis of patients with atrial fibrillation or atrial flutter, the IRR was lower in all cancer sites (IRR, 0.62; 95% CI, 0.59-0.65) and in prevalent sites (lung, 0.39 [95% CI, 0.33-0.46]; prostate, 0.60 [95% CI, 0.55-0.66]; breast, 0.72 [95% CI, 0.59-0.87]; and colon, 0.71 [95% CI, 0.63-0.81]).

CONCLUSIONS AND RELEVANCE:

Warfarin use may have broad anticancer potential in a large, population-based cohort of persons older than 50 years. This finding could have important implications for the selection of medications for patients needing anticoagulation.

 

Long-term Sustainability of Diabetes Prevention Approaches: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

Haw JS, Galaviz KI, Straus AN, Kowalski AJ, Magee MJ, Weber MB, Wei J, Narayan KMV, Ali MK.

JAMA Intern Med. 2017 Dec 1;177(12):1808-1817. doi: 10.1001/jamainternmed.2017.6040. Review.

PMID: 29114778

Abstract

IMPORTANCE:

Diabetes prevention is imperative to slow worldwide growth of diabetes-related morbidity and mortality. Yet the long-term efficacy of prevention strategies remains unknown.

OBJECTIVE:

To estimate aggregate long-term effects of different diabetes prevention strategies on diabetes incidence.

DATA SOURCES:

Systematic searches of MEDLINE, EMBASE, Cochrane Library, and Web of Science databases. The initial search was conducted on January 14, 2014, and was updated on February 20, 2015. Search terms included prediabetes, primary prevention, and risk reduction.

STUDY SELECTION:

Eligible randomized clinical trials evaluated lifestyle modification (LSM) and medication interventions (>6 months) for diabetes prevention in adults (age ≥18 years) at risk for diabetes, reporting between-group differences in diabetes incidence, published between January 1, 1990, and January 1, 2015. Studies testing alternative therapies and bariatric surgery, as well as those involving participants with gestational diabetes, type 1 or 2 diabetes, and metabolic syndrome, were excluded.

DATA EXTRACTION AND SYNTHESIS:

Reviewers extracted the number of diabetes cases at the end of active intervention in treatment and control groups. Random-effects meta-analyses were used to obtain pooled relative risks (RRs), and reported incidence rates were used to compute pooled risk differences (RDs).

MAIN OUTCOMES AND MEASURES:

The main outcome was aggregate RRs of diabetes in treatment vs control participants. Treatment subtypes (ie, LSM components, medication classes) were stratified. To estimate sustainability, post-washout and follow-up RRs for medications and LSM interventions, respectively, were examined.

RESULTS:

Forty-three studies were included and pooled in meta-analysis (49 029 participants; mean [sD] age, 57.3 [8.7] years; 48.0% [n = 23 549] men): 19 tested medications; 19 evaluated LSM, and 5 tested combined medications and LSM. At the end of the active intervention (range, 0.5-6.3 years), LSM was associated with an RR reduction of 39% (RR, 0.61; 95% CI, 0.54-0.68), and medications were associated with an RR reduction of 36% (RR, 0.64; 95% CI, 0.54-0.76). The observed RD for LSM and medication studies was 4.0 (95% CI, 1.8-6.3) cases per 100 person-years or a number-needed-to-treat of 25. At the end of the washout or follow-up periods, LSM studies (mean follow-up, 7.2 years; range, 5.7-9.4 years) achieved an RR reduction of 28% (RR, 0.72; 95% CI, 0.60-0.86); medication studies (mean follow-up, 17 weeks; range, 2-52 weeks) showed no sustained RR reduction (RR, 0.95; 95% CI, 0.79-1.14).

CONCLUSIONS AND RELEVANCE:

In adults at risk for diabetes, LSM and medications (weight loss and insulin-sensitizing agents) successfully reduced diabetes incidence. Medication effects were short lived. The LSM interventions were sustained for several years; however, their effects declined with time, suggesting that interventions to preserve effects are needed.

Edited by AlPater

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Testosterone Therapy and Glucose Homeostasis in Men with Testosterone Deficiency (Hypogonadism).

Saad F.

Adv Exp Med Biol. 2017;1043:527-558. doi: 10.1007/978-3-319-70178-3_23.

PMID: 29224109

Abstract

Since the early 1990s, it has been recognized that testosterone (T) levels are lower in men with type 2 diabetes mellitus (T2DM) compared with nondiabetic men (controls). Hypogonadism has been reported in approximately 50% of men with T2DM with robust correlations with measures of obesity, such as waist circumference and body mass index (BMI). In longitudinal studies, hypogonadism has been identified as a predictor of incident T2DM. Experimental withdrawal of T led to acute decreased insulin sensitivity, which can be reversed by normalization of T concentrations. Androgen deprivation therapy, commonly used in men with advanced prostate cancer, increases the risk of incident T2DM significantly.While short-term studies of T therapy in hypogonadal men with T2DM show only minor effects, long-term administration of T leads to meaningful and sustained improvements of glycemic control with parallel reductions in body weight and waist circumference. The more insulin-resistant and obese a patient is at the time of initiation of T therapy, the more improvements are noted. The observed effects are likely mediated by the increase in lean body mass invariably achieved by T therapy, as well as the improvement in energy and motivation, referred to as the psychotropic effects of T. As recommended by various guidelines, measuring T levels and, if indicated, restoring men's T levels into the normal physiological range can have a substantial impact on ameliorating T2DM in hypogonadal men.

 

Changes in job strain and subsequent weight gain: a longitudinal study, based on the Danish Nurse Cohort.

Vesterlund GK, Keller AC, Heitmann BL.

Public Health Nutr. 2017 Dec 10:1-8. doi: 10.1017/S136898001700355X. [Epub ahead of print]

PMID: 29223170

Abstract

OBJECTIVE:

Obesity as well as job strain is increasing, and job strain might contribute to weight gain. The objective of the current study was to examine associations between longitudinal alterations in the components of job strain and subsequent weight gain.

DESIGN:

The study was designed as a prospective cohort study with three questionnaire surveys enabling measurement of job-strain alterations over 6 years and subsequent measurements of weight gain after further 10 years of follow-up. ANCOVA and trend analyses were conducted. Job demands were measured as job busyness and speed, and control as amount of influence.

SETTING:

Employed nurses in Denmark.

SUBJECTS:

We included a sub-sample of 6188 female nurses from the Danish Nurse Cohort, which consisted of the nurses who participated in surveys in 1993, 1999 and 2009.

RESULTS:

A linear trend in weight gain was seen in nurses who were often busy in 1999 between those who were rarely v. sometimes v. often busy in 1993 (P=0·03), with the largest weight gain in individuals with sustained high busyness in both years. Loss of influence between 1993 and 1999 was associated with larger subsequent weight gain than sustained high influence (P=0·003) or sustained low influence (P=0·02). For speed, no associations were found.

CONCLUSIONS:

Busyness, speed and influence differed in their relationship to subsequent weight gain. A decrease in job influence and a sustained burden of busyness were most strongly related to subsequent weight gain. Focus on job strain reduction and healthy diet is essential for public health.

KEYWORDS:

Epidemiology; Job strain; Obesity; Psychological risk factors; Weight gain

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Ethical concerns regarding animal use mediate the relationship between variety of pets owned in childhood and vegetarianism in adulthood.

Heiss S, Hormes JM.

Appetite. 2017 Dec 7. pii: S0195-6663(17)31290-4. doi: 10.1016/j.appet.2017.12.005. [Epub ahead of print]

PMID: 29225142

Abstract

Plant-based and vegetarian diets have been shown to have diverse health and environmental benefits and also serve to reduce farmed animal exploitation. It is therefore worthwhile to gain a better understanding of the factors that play a role in the decision to refrain from animal products. Past studies have shown that childhood pet ownership predicts the likelihood of adherence to a vegetarian diet in adulthood. Building on this research, we tested the hypothesis that the number of different types of pets owned in childhood is positively associated with degree of restriction of animal products in adulthood, and that this relationship is mediated by pro-animal attitudes. A self-selected convenience sample of 325 participants (77.2% female; mean age = 30.23 ± 12.5) reported on their vegetarian status and completed the Animal Advocacy Scale and Child Pet Ownership Questionnaire. The number of different pets owned in childhood was positively correlated with degree of vegetarianism in adulthood (p < 0.001), but was no longer a significant predictor when controlling for moral opposition to animal exploitation. A significant Sobel test (z = 4.36; p < 0.001) confirmed the presence of full mediation. Findings support the hypothesis that individuals who owned a greater variety of pets in childhood endorse more concerns regarding animal use. This, in turn, appears to predict the decision to refrain from animal products in adulthood. The possibility that an enhanced ability to generalize empathy from companion to laboratory, farm, and wildlife animals underlies this relationship should be examined in future research.

KEYWORDS:

Animal advocacy; Companion animals; Pets; Veganism; Vegetarianism

 

Human longevity: 25 genetic loci associated in 389,166 UK biobank participants.

Pilling LC, Kuo CL, Sicinski K, Tamosauskaite J, Kuchel GA, Harries LW, Herd P, Wallace R, Ferrucci L, Melzer D.

Aging (Albany NY). 2017 Dec 6. doi: 10.18632/aging.101334. [Epub ahead of print]

PMID: 29227965

http://www.aging-us.com/article/101334/text#fulltext

https://s3-us-west-1.amazonaws.com/paperchase-aging/pdf/h7MMoLuzjEgGRDGza.pdf

Abstract

We undertook a genome-wide association study (GWAS) of parental longevity in European descent UK Biobank participants. For combined mothers' and fathers' attained age, 10 loci were associated (p<5*10-8), including 8 previously identified for traits including survival, Alzheimer's and cardiovascular disease. Of these, 4 were also associated with longest 10% survival (mothers age ≥90 years, fathers ≥87 years), with 2 additional associations including MC2R intronic variants (coding for the adrenocorticotropic hormone receptor). Mother's age at death was associated with 3 additional loci (2 linked to autoimmune conditions), and 8 for fathers only. An attained age genetic risk score associated with parental survival in the US Health and Retirement Study and the Wisconsin Longitudinal Study and with having a centenarian parent (n=1,181) in UK Biobank. The results suggest that human longevity is highly polygenic with prominent roles for loci likely involved in cellular senescence and inflammation, plus lipid metabolism and cardiovascular conditions. There may also be gender specific routes to longevity.

KEYWORDS:

1417; GWAS; genetic; human; longevity

 

N-acetylcysteine (NAC) ameliorates Epstein-Barr virus latent membrane protein 1 induced chronic inflammation.

Gao X, Lampraki EM, Al-Khalidi S, Qureshi MA, Desai R, Wilson JB.

PLoS One. 2017 Dec 11;12(12):e0189167. doi: 10.1371/journal.pone.0189167. eCollection 2017.

PMID: 29228057

Abstract

Chronic inflammation results when the immune system responds to trauma, injury or infection and the response is not resolved. It can lead to tissue damage and dysfunction and in some cases predispose to cancer. Some viruses (including Epstein-Barr virus (EBV)) can induce inflammation, which may persist even after the infection has been controlled or cleared. The damage caused by inflammation, can itself act to perpetuate the inflammatory response. The latent membrane protein 1 (LMP1) of EBV is a pro-inflammatory factor and in the skin of transgenic mice causes a phenotype of hyperplasia with chronic inflammation of increasing severity, which can progress to pre-malignant and malignant lesions. LMP1 signalling leads to persistent deregulated expression of multiple proteins throughout the mouse life span, including TGFα S100A9 and chitinase-like proteins. Additionally, as the inflammation increases, numerous chemokines and cytokines are produced which promulgate the inflammation. Deposition of IgM, IgG, IgA and IgE and complement activation form part of this process and through genetic deletion of CD40, we show that this contributes to the more tissue-destructive aspects of the phenotype. Treatment of the mice with N-acetylcysteine (NAC), an antioxidant which feeds into the body's natural redox regulatory system through glutathione synthesis, resulted in a significantly reduced leukocyte infiltrate in the inflamed tissue, amelioration of the pathological features and delay in the inflammatory signature measured by in vivo imaging. Reducing the degree of inflammation achieved through NAC treatment, had the knock on effect of reducing leukocyte recruitment to the inflamed site, thereby slowing the progression of the pathology. These data support the idea that NAC could be considered as a treatment to alleviate chronic inflammatory pathologies, including post-viral disease. Additionally, the model described can be used to effectively monitor and accurately measure therapies for chronic inflammation.

 

Effect of high-dose oral multivitamins and minerals in participants not treated with statins in the randomized Trial to Assess Chelation Therapy (TACT).

Adherence to Mediterranean Diet and All-Cause Mortality After an Episode of Acute Heart Failure: Results of the MEDIT-AHF Study.

Flaxseed supplementation on glucose control and insulin sensitivity: a systematic review and meta-analysis of 25 randomized, placebo-controlled trials.

Mohammadi-Sartang M, Sohrabi Z, Barati-Boldaji R, Raeisi-Dehkordi H, Mazloom Z.

Nutr Rev. 2017 Dec 8. doi: 10.1093/nutrit/nux052. [Epub ahead of print]

PMID: 29228348

Abstract

CONTEXT:

The results of human clinical trials investigating the effects of flaxseed on glucose control and insulin sensitivity are inconsistent.

OBJECTIVE:

The present study aimed to systematically review and analyze randomized controlled trials assessing the effects of flaxseed consumption on glycemic control.

DATA SOURCES:

PubMed, Medline via Ovid, SCOPUS, EMBASE, and ISI Web of Sciences databases were searched up to November 2016.

STUDY SELECTION:

Clinical trials in which flaxseed or its products were administered as an intervention were included.

DATA EXTRACTION:

The outcomes were fasting blood glucose, insulin concentration, insulin resistance (HOMA-IR), insulin sensitivity (QUIKI), and hemoglobin A1c (HbA1c).

RESULTS:

A total of 25 randomized clinical trials (30 treatment arms) were included. Meta-analysis suggested a significant association between flaxseed supplementation and a reduction in blood glucose (weighted mean difference [WMD], -2.94 mg/dL; 95%CI,  -5.31 to - 0.56; P = 0.015), insulin levels (WMD,  -7.32 pmol/L; 95%CI, -11.66 to -2.97; P = 0.001), and HOMA-IR index (WMD, -0.49; 95%CI,: -0.78 to - 0.20; P = 0.001) and an increase in QUIKI index (WMD, 0.019; 95%CI, 0.008-0.031; P = 0.001). No significant effect on HbA1c (WMD, -0.045%; 95%CI, -0.16 to - 0.07; P = 0.468) was found. In subgroup analysis, a significant reduction in blood glucose, insulin, and HOMA-IR and a significant increase in QUIKI were found only in studies using whole flaxseed but not flaxseed oil and lignan extract. Furthermore, a significant reduction was observed in insulin levels and insulin sensitivity indexes only in the subset of trials lasting ≥12 weeks.

CONCLUSIONS:

Whole flaxseed, but not flaxseed oil and lignan extract, has significant effects on improving glycemic control. Further studies are needed to determine the benefits of flaxseed on glycemic parameters. The protocol for this systematic review was registered in the international prospective register of systematic reviews (PROSPERO) database (http://www.crd.york.ac.uk/PROSPERO; registration no: CRD42016043500).

KEYWORDS:

flaxseed; glucose; insulin; insulin resistance; lignan

 

Miró Ò, Estruch R, Martín-Sánchez FJ, Gil V, Jacob J, Herrero-Puente P, Herrera Mateo S, Aguirre A, Andueza JA, Llorens P; ICA-SEMES Research Group.

JACC Heart Fail. 2017 Nov 27. pii: S2213-1779(17)30683-2. doi: 10.1016/j.jchf.2017.09.020. [Epub ahead of print]

PMID: 29226819

Abstract

OBJECTIVES:

The authors sought to evaluate clinical outcomes of patients after an episode of acute heart failure (AHF) according to their adherence to the Mediterranean diet (MedDiet).

BACKGROUND:

It has been proved that MedDiet is a useful tool in primary prevention of cardiovascular diseases. However, it is unknown whether adherence to MedDiet is associated with better outcomes in patients who have already experienced an episode of AHF.

METHODS:

We designed a prospective study that included consecutive patients diagnosed with AHF in 7 Spanish emergency departments (EDs). Patients were included if they or their relatives were able to answer a 14-point score of adherence to the MedDiet, which classified patients as adherents (≥9 points) or nonadherents (≤8 points). The primary endpoint was all-cause mortality at the end of follow-up, and secondary endpoints were 1-year ED revisit without hospitalization, rehospitalization, death, and a combined endpoint of all these variables for patients discharged after the index episode. Unadjusted and adjusted hazard ratios (HRs) were calculated.

RESULTS:

We included 991 patients (mean age of 80 ± 10 years, 57.8% women); 523 (52.9%) of whom were adherent to the MedDiet. After a mean follow-up period of 2.1 ± 1.3 years, no differences were observed in survival between adherent and nonadherent patients (HR of adherents [hradh] = 0.86; 95% confidence interval [CI]: 0.73 to 1.02). The 1-year cumulative ED revisit for the whole cohort was 24.5% (HRadh = 1.10; 95% CI: 0.84 to 1.42), hospitalization 43.7% (HRadh = 0.74; 95% CI: 0.61 to 0.90), death 22.7% (HRadh = 1.05; 95% CI: 0.8 to 1.38), and combined endpoint 66.8% (HRadh = 0.89; 95% CI: 0.76 to 1.04). Adjustment by age, hypertension, peripheral arterial disease, previous episodes of AHF, treatment with statins, air-room pulsioxymetry, and need for ventilation support in the ED rendered similar results, with no statistically significant differences in mortality (HRadh = 0.94; 95% CI: 0.80 to 1.13) and persistence of lower 1-year hospitalization for adherents (HRadh = 0.76; 95% CI: 0.62 to 0.93).

CONCLUSIONS:

Adherence to the MedDiet did not influence long-term mortality after an episode of AHF, but it was associated with decreased rates of rehospitalization during the next year.

KEYWORDS:

Mediterranean diet; acute heart failure; cardiovascular disease; diet; heart failure; outcome

 

Issa OM, Roberts R, Mark DB, Boineau R, Goertz C, Rosenberg Y, Lewis EF, Guarneri E, Drisko J, Magaziner A, Lee KL, Lamas GA.

Am Heart J. 2018 Jan;195:70-77. doi: 10.1016/j.ahj.2017.09.002. Epub 2017 Sep 8.

PMID: 29224648

Abstract

IMPORTANCE:

In a prespecified subgroup analysis of participants not on statin therapy at baseline in the TACT, a high-dose complex oral multivitamins and multimineral regimen was found to have a large unexpected benefit compared with placebo. The regimen tested was substantially different from any vitamin regimen tested in prior clinical trials.

OBJECTIVE:

To explore these results, we performed detailed additional analyses of participants not on statins at enrollment in TACT.

DESIGN:

TACT was a factorial trial testing chelation treatments and a 28-component high-dose oral multivitamins and multiminerals regimen versus placebo in post-myocardial infarction (MI) patients 50 years or older.

PARTICIPANTS:

There were 460 (27%) of 1,708 TACT participants not taking statins at baseline, 224 (49%) were in the active vitamin group and 236 (51%) were in the placebo group.

SETTING:

Patients were enrolled at 134 sites around the United States and Canada.

INTERVENTION:

Daily high-dose oral multivitamins and multiminerals (6 tablets, active or placebo).

MAIN OUTCOME:

The primary end point of TACT was time to the first occurrence of any component of the composite end point: all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for angina.

RESULTS:

The primary end point occurred in 137 nonstatin participants (30%), of which 51 (23%) of 224 were in the active group and 86 (36%) of 236 were taking placebo (hazard ratio, 0.62; 95% confidence interval, 0.44-0.87; P=.006). Results in the key TACT secondary end point, a combination of cardiovascular mortality, stroke, or recurrent MI, was consistent in favoring the active vitamin group (hazard ratio, 0.46; 95% confidence interval, 0.28-0.75; P=.002). Multiple end point analyses were consistent with these results.

CONCLUSION AND RELEVANCE:

High-dose oral multivitamin and multimineral supplementation seem to decrease combined cardiac events in a stable, post-MI population not taking statin therapy at baseline. These unexpected findings are being retested in the ongoing TACT2.

 

Enhancing nutrition with pulses: defining a recommended serving size for adults.

Marinangeli CPF, Curran J, Barr SI, Slavin J, Puri S, Swaminathan S, Tapsell L, Patterson CA.

Nutr Rev. 2017 Nov 30. doi: 10.1093/nutrit/nux058. [Epub ahead of print]

PMID: 29202192

https://academic.oup.com/nutritionreviews/article/75/12/990/4675268

https://watermark.silverchair.com/nux058.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAcAwggG8BgkqhkiG9w0BBwagggGtMIIBqQIBADCCAaIGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMtBNXtZFQkcHO2iDjAgEQgIIBcxM_XeAzndJ4PFMu2F5sKRLmLXcJ2XQE5W5TcBJtOh5365eiQUxW0ZdxbALiJ4jfLFyTgC-4f_vY6AhpW2tsAEXue1TQXC-uSxzBzQpFikZB6sU84cTE21L-gdpNQlvfTnlRIDlgeKged131oKAOEFpXJtXhGyrdswrCIms3N6EyU3z9ENKypfZ1bIqqMqSiJ51vsivsz7xrccuQlf9Q0C7N56Mt59cwwaqf87tXJu42CYgqMnb43afiMHtjizVppHU1EDoNJa2pXJ4bPKel1At8JSouNcoD49RGAKQcWV-YKJzUcEDaiMiAQqu45Oo1kLMCUCY4sHR5LKCgnctri2U7K6A-M_GTE-l45V1ssiXKfqgTGrgTawDxPYeQNF16muNPWjEQs-e4CnFrZ-JwLbI3ozhJj5bLmxQaZ6JHBBDIRqhqBM3ZC47Fe2DDohP1HylgTZD3ekK0lwl9bEglGojeS6y54GHkM9c53VWOMXX-l7s5

Abstract

Pulses, defined as dry-harvested leguminous crops, include several varieties of beans, peas, lentils, and chickpeas. There is no consensus around a recommended serving size of pulses within a balanced diet, which prevents the development of transregional strategies that rely on consistent messaging to drive increases in consumption. The purpose of this review is to define and disseminate an appropriate target for a minimum serving size of pulses on any given day that can be used in international or collaborative strategies to promote the consumption of pulses. Relevant data were reviewed to examine dietary guidelines across jurisdictions, determine consumption levels of pulses across the globe, evaluate the nutritional composition of pulses in the context of dietary nutrient insufficiency, and assess the impact of pulses on dietary quality. Across a variety of pulses, 100 g of cooked pulses aligned with most regional serving sizes for pulses and provides significant levels of nutrients that are underconsumed by specific age-sex groups. Moreover, 100 g of pulses provides a number of nutrients that qualify for nutrient content claims under regional regulatory frameworks. The data demonstrate that 100 g or 125 mL (0.5 metric cup) of cooked pulses is a reasonable target for aligning strategies that promote the dietary and nutritional attributes of these legumes.

KEYWORDS:

beans; chickpeas; lentils; nutrient recommendation; nutrition; peas; pulses; regulatory

 

Consideration of insects as a source of dietary protein for human consumption.

Churchward-Venne TA, Pinckaers PJM, van Loon JJA, van Loon LJC.

Nutr Rev. 2017 Nov 30. doi: 10.1093/nutrit/nux057. [Epub ahead of print]

PMID: 29202184

Abstract

Consumption of sufficient dietary protein is fundamental to muscle mass maintenance and overall health. Conventional animal-based protein sources such as meat (ie, beef, pork, lamb), poultry, fish, eggs, and dairy are generally considered high-quality sources of dietary protein because they meet all of the indispensable amino-acid requirements for humans and are highly digestible. However, the production of sufficient amounts of conventional animal-based protein to meet future global food demands represents a challenge. Edible insects have recently been proposed as an alternative source of dietary protein that may be produced on a more viable and sustainable commercial scale and, as such, may contribute to ensuring global food security. This review evaluates the protein content, amino-acid composition, and digestibility of edible insects and considers their proposed quality and potential as an alternative protein source for human consumption.

KEYWORDS:

amino-acid content; dietary protein; edible insects; protein digestibility

 

Interindividual variability in gut microbiota and host response to dietary interventions.

Healey GR, Murphy R, Brough L, Butts CA, Coad J.

Nutr Rev. 2017 Dec 1;75(12):1059-1080. doi: 10.1093/nutrit/nux062.

PMID: 29190368

Abstract

Dysbiosis is linked to human disease; therefore, gut microbiota modulation strategies provide an attractive means of correcting microbial imbalance to enhance human health. Because diet has a major influence on the composition, diversity, and metabolic capacity of the gut microbiota, numerous dietary intervention studies have been conducted to manipulate the gut microbiota to improve host outcomes and reduce disease risk. Emerging evidence suggests that interindividual variability in gut microbiota and host responsiveness exists, making it difficult to predict gut microbiota and host response to a given dietary intervention. This may, in turn, have implications on the consistency of results among studies and the perceived success or true efficacy of a dietary intervention in eliciting beneficial changes to the gut microbiota and human health.

KEYWORDS:

gut microbiota; habitual dietary intake; host outcomes; interindividual variability; responsiveness

 

Dietary fat and total energy intake modifies the association of genetic profile risk score on obesity: evidence from 48 170 UK Biobank participants.

Celis-Morales CA, Lyall DM, Gray SR, Steell L, Anderson J, Iliodromiti S, Welsh P, Guo Y, Petermann F, Mackay DF, Bailey MES, Pell JP, Gill JMR, Sattar N.

Int J Obes (Lond). 2017 Dec;41(12):1761-1768. doi: 10.1038/ijo.2017.169. Epub 2017 Jul 24.

PMID: 28736445

Abstract

BACKGROUND:

Obesity is a multifactorial condition influenced by both genetics and lifestyle. The aim of this study was to investigate whether the association between a validated genetic profile risk score for obesity (GPRS-obesity) and body mass index (BMI) or waist circumference (WC) was modified by macronutrient intake in a large general population study.

METHODS:

This study included cross-sectional data from 48 170 white European adults, aged 37-73 years, participating in the UK Biobank. Interactions between GPRS-obesity and macronutrient intake (including total energy, protein, fat, carbohydrate and dietary fibre intake) and its effects on BMI and WC were investigated.

RESULTS:

The 93-single-nucleotide polymorphism (SNP) GPRS was associated with a higher BMI (β: 0.57 kg m-2 per s.d. increase in GPRS (95% confidence interval: 0.53-0.60); P=1.9 × 10-183) independent of major confounding factors. There was a significant interaction between GPRS and total fat intake (P(interaction)=0.007). Among high-fat-intake individuals, BMI was higher by 0.60 (0.52, 0.67) kg m-2 per s.d. increase in GPRS-obesity; the change in BMI with GPRS was lower among low-fat-intake individuals (β: 0.50 (0.44, 0.57) kg m-2). Significant interactions with similar patterns were observed for saturated fat intake (high β: 0.66 (0.59, 0.73) versus low β: 0.49 (0.42, 0.55) kg m-2, P(interaction)=2 × 10-4) and for total energy intake (high β: 0.58 (0.51, 0.64) versus low β: 0.49 (0.42, 0.56) kg m-2, P(interaction)=0.019), but not for protein intake, carbohydrate intake and fibre intake (P(interaction) >0.05). The findings were broadly similar using WC as the outcome.

CONCLUSIONS:

These data suggest that the benefits of reducing the intake of fats and total energy intake may be more important in individuals with high genetic risk for obesity.

 

Effects of vitamin C supplementation on glycaemic control: a systematic review and meta-analysis of randomised controlled trials.

Ashor AW, Werner AD, Lara J, Willis ND, Mathers JC, Siervo M.

Eur J Clin Nutr. 2017 Dec;71(12):1371-1380. doi: 10.1038/ejcn.2017.24. Epub 2017 Mar 15. Review.

PMID: 28294172

Abstract

Randomised controlled trials (RCTs) have observed contrasting results on the effects of vitamin C on circulating biomarkers of glycaemic and insulin regulation. We conducted a systematic review and meta-analysis of RCTs testing the effect of vitamin C administration on glucose, HbA1c and insulin concentrations. Four databases (PubMed, Embase, Scopus and Cochrane Library) were used to retrieve RCTs published from inception until April 2016 and testing the effects of vitamin C in adult participants. The screening of 2008 articles yielded 22 eligible studies (937 participants). Overall, vitamin C did not modify glucose, HbA1c and insulin concentrations. However, subgroup analyses showed that vitamin C significantly reduced glucose concentrations (-0.44 mmol/l, 95% CI: -0.81, -0.07, P=0.01) in patients with type 2 diabetes and in interventions with a duration greater than 30 days (-0.53%, 95% CI: -0.79, -0.10, P=0.02). Vitamin C administration had greater effects on fasting (-13.63 pmol/l, 95% CI: -22.73, -4.54, P<0.01) compared to postprandial insulin concentration. Meta-regression analyses showed that age was a modifier of the effect of vitamin C on insulin concentration. Furthermore, the effect size was associated with baseline BMI and plasma glucose levels, and with the duration of the intervention. In conclusion, greater reduction in glucose concentrations observed in patients with diabetes, older individuals and with more prolonged supplementation. Personalised interventions with vitamin C may represent a feasible future strategy to enhance benefits and efficacy of interventions. Nevertheless, results need to be interpreted cautiously due to limitations in the primary studies analysed.

 

Leisure time sedentary behavior, physical activity and frequency of protein consumption on lower extremity strength and lean mass.

Loprinzi PD, Loenneke JP, Hamilton DL.

Eur J Clin Nutr. 2017 Dec;71(12):1399-1404. doi: 10.1038/ejcn.2017.101. Epub 2017 Jun 28.

PMID: 28656974

Abstract

BACKGROUND/OBJECTIVES:

The purpose of this study was to evaluate the independent and combined associations of moderate-to-vigorous physical activity (MVPA), leisure time sedentary behavior and daily protein consumption on lower extremity muscular strength and lean mass.

SUBJECTS/METHODS:

Data from the 1999-2002 NHANES were utilized (N=1080 adults 50-85 y). Leg lean mass was estimated from dual-energy x-ray absorptiometry scans. Knee extensor strength was assessed objectively using the Kin Com MP dynamometer. MVPA and leisure time sedentary behavior were assessed via questionnaire, with the number of meals per day of ⩾30 g of protein per meal assessed via a 'multiple pass' 24-h dietary interview.

RESULTS:

Meeting MVPA guidelines (β=16.3, P=0.02) and consuming at least two meals per day of ⩾30 g of protein per meal (β=28.8, P=0.02) were independently associated with greater lower extremity strength, whereas sedentary behavior was not (β=11.6, P=0.23). Finally, there was no evidence of a three-way interaction of these behaviors on lower extremity strength (β=-8.7; P=0.70) or lower extremity lean mass (β=144.5; P=0.75).

CONCLUSIONS:

Although MVPA and frequency of protein consumption of ⩾30 g of protein per meal were independently associated with lower extremity lean mass and strength, the results of the present study do not provide evidence to suggest that there is a three-way interplay between MVPA, sedentary behavior and frequency of protein consumption ⩾30 g of protein per meal on lower extremity lean mass and strength.

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Dispersal limitation promotes the diversification of the mammalian gut microbiota.

Moeller AH, Suzuki TA, Lin D, Lacey EA, Wasser SK, Nachman MW.

Proc Natl Acad Sci U S A. 2017 Dec 11. pii: 201700122. doi: 10.1073/pnas.1700122114. [Epub ahead of print]

PMID: 29229828

Abstract

The gut bacterial communities of mammals have profound effects on host fitness, but the processes that generate and maintain gut bacterial diversity remain poorly understood. We mapped compositional variation (i.e., β-diversity) in the gut microbiotas of 136 pairs of wild mammalian species living throughout the Americas to assess how the distribution of mammals across geographic space influences the diversification of their gut bacteria. Comparing the gut microbiotas of sympatric and allopatric mammalian populations provided insights into the flow of gut bacteria within and between mammalian communities, revealing that spatial limits on bacterial dispersal promote β-diversity between the gut microbiotas of mammalian species. Each geographic locale displayed a unique gut-microbiota composition that could not be fully explained by the diets and phylogenetic histories of the resident mammalian hosts, indicating that some gut bacteria are geographically restricted. Across the western hemisphere, the compositional overlap between the gut microbiotas of allopatric mammalian populations decayed exponentially with the geographic distance separating the hosts. The relationship between geographic distances among hosts and compositional differences among their gut microbiotas was independent of dietary and phylogenetic divergence among hosts. Within mammalian communities, we observed widespread sharing of gut bacteria between predator-prey host-species pairs, indicating horizontal transfer of gut bacteria through mammalian food chains. Collectively, these results indicate that compositional differences between the gut microbiotas of mammalian taxa are generated and maintained by limits to bacterial dispersal imposed by physical distance between hosts.

KEYWORDS:

biogeography; food web; metacommunity; microbiome; vertebrate

 

Legume Consumption and All-Cause and Cardiovascular Disease Mortality.

Li H, Li J, Shen Y, Wang J, Zhou D.

Biomed Res Int. 2017;2017:8450618. doi: 10.1155/2017/8450618. Epub 2017 Nov 2. Review.

PMID: 29230416

Abstract

BACKGROUND:

Legume consumption is suggested to have protective effects against cardiovascular disease (CVD) mortality in the general population, but the results have been equivocal. We conducted a meta-analysis of prospective cohort studies to assess the association between legume consumption and risk of CVD mortality and all-cause mortality.

METHODS AND RESULTS:

Medline (via Ovid) and EMBASE (via Ovid) databases were searched through April 2017 to identify eligible studies. The two authors independently extracted the data and the adjusted relative risks (RRs) and 95% confidence intervals (CIs) were pooled by using a random-effects model. A total of 6 studies were identified, including the sizes of participants ranging from 23,601 to 59,485 with a sum of 21,8997. Comparing the highest category with the lowest, the pooled RR (95% CI) was 0.96 (0.86-1.06) for CVD mortality and 0.93 (0.87-0.99) for all-cause mortality.

CONCLUSIONS:

Results from the current study show that high legume intakes are associated with lower risk of all-cause mortality. In consideration of the small number of studies, the evidence for assessing relationship between legumes intake and risk of all-cause mortality remains inclusive and warrants further study in the future. Further, consuming legumes does not increase the risk of CVD mortality.

 

Dietary fat intake and risk of esophageal carcinoma: a meta-analysis of observational studies.

He D, Huang X, Wang ZP, Chen D, Chen J, Duan CY.

Oncotarget. 2017 Oct 3;8(58):99049-99056. doi: 10.18632/oncotarget.21462. eCollection 2017 Nov 17.

PMID: 29228750

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=21462&path%5B%5D=68210

Abstract

Dietary fat intake is potentially associated with the onset of esophageal carcinoma (EC), but evidence from observational studies has remained unclear. This study aimed to evaluate the role of fat intake in the development of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). A systematic search was conducted in PubMed and Web of Science to identify all relevant studies. Study-specific relative risks (RR) for the highest versus the lowest intake categories and 95% confidence intervals (CI) were pooled using a random-effects model. Seventeen case-control studies (2058 EAC cases, 1581 ESCC cases and 11696 controls) and two prospective cohort studies (494, 978 participants and 630 EAC cases and 215 ESCC cases) were identified. In EAC, the RRs (95% CI) were 1.69 (1.14-2.50) for total fat intake, 1.88 (1.28-2.77) for saturated fat (SFA) intake, 1.04 (0.86-1.27) for polyunsaturated fat (PUFA) intake and 1.70 (1.01-2.84) for monounsaturated fat (MUFA) intake. In ESCC, the RRs (95% CI) were 1.12 (0.84-1.51) for total fat, 1.38 (0.91-2.08) for SFA, 0.95 (0.55-1.62) for PUFA and 1.04 (0.65-1.66) for MUFA. In conclusion, total fat, SFA and MUFA intake were associated with EAC risk, but fat intake showed no significant association with ESCC risk. Large-scale prospective cohort studies are needed to confirm our findings.

KEYWORDS:

esophageal carcinoma; fat intake; meta-analysis; risk

 

Frequent sauna bathing may reduce the risk of pneumonia in middle-aged Caucasian men: The KIHD prospective cohort study.

Kunutsor SK, Laukkanen T, Laukkanen JA.

Respir Med. 2017 Nov;132:161-163. doi: 10.1016/j.rmed.2017.10.018. Epub 2017 Oct 23.

PMID: 29229091

Abstract

OBJECTIVE:

Emerging evidence suggests sauna bathing to be linked with numerous health benefits. Having frequent sauna baths has been found to be associated with reduced risk of acute and chronic disease conditions. Sauna bathing may reduce the risk of respiratory diseases; however, the evidence is uncertain. We aimed to assess the association of frequency of sauna bathing with risk of pneumonia.

METHODS:

Baseline sauna bathing habits were assessed by administration of questionnaires in a prospective cohort of 2210 men aged 42-61 years.

RESULTS:

During a median follow-up of 25.6 years, 375 hospital diagnosed cases of pneumonia were recorded. In age-adjusted analyses, the hazard ratios (HRs) 95% confidence intervals (CIs) of pneumonia were 0.67 (0.53-0.83) and 0.53 (0.34-0.84) for participants who had 2-3 and ≥4 sauna sessions per week respectively compared with participants who had ≤ 1 sauna session per week. After further adjustment for several major risk factors, the HRs were 0.69 (0.55-0.86) and 0.56 (0.35-0.88) respectively. The associations remained on additional adjustment for total energy intake, socioeconomic status, physical activity, and C-reactive protein, 0.72 (0.57-0.90) and 0.63 (0.39-1.00) respectively.

CONCLUSIONS:

Frequent sauna baths is associated with reduced pneumonia risk in a middle-aged male Caucasian population.

KEYWORDS:

Cohort study; Pneumonia; Sauna

 

Comparison of the effects of flaxseed oil and sunflower seed oil consumption on serum glucose, lipid profile, blood pressure, and lipid peroxidation in patients with metabolic syndrome.

Akrami A, Nikaein F, Babajafari S, Faghih S, Yarmohammadi H.

J Clin Lipidol. 2017 Nov 20. pii: S1933-2874(17)30513-5. doi: 10.1016/j.jacl.2017.11.004. [Epub ahead of print]

PMID: 29229363

Abstract

BACKGROUND:

Metabolic syndrome (MetSyn) increases the risk of type II diabetes and morbidity and mortality due to cardiovascular diseases. Flaxseed oil (FO), as a functional food, is one of the major vegetal sources of essential omega-3 fatty acids.

OBJECTIVE:

This study aimed to compare the effects of consumption of FO and sunflower seed oil (SO) on lipid peroxidation and other symptoms of MetSyn.

METHODS:

This randomized controlled interventional trial was conducted on 60 volunteers aged 30 to 60 years who were diagnosed with MetSyn in Shiraz, Iran. The participants who fulfilled the inclusion criteria were randomly assigned to SO (n = 30, receiving 25 mL/d SO) and FO (n = 30, receiving 25 ml/d FO) groups using block randomization. The diets were identical for all the participants. Blood pressure (BP), serum lipid, fasting blood sugar, and malondialdehyde were measured at baseline and at the end of week 7.

RESULT:

The results showed no significant difference between the 2 groups regarding blood lipid levels and fasting blood sugar at the end of the study. However, significant reductions in total cholesterol, low-density lipoprotein cholesterol (5.6% in FO and 10.8% in SO), and triglyceride levels were seen within each group after treatment with FO and SO (P < .05). Nonetheless, between-group changes were significant (<0.05) for systolic BP (mean [±standard deviation {SD}] changes were -14.0 ± 22.41 in the FO group [P = .004] and 0.92 ± 8.70 in the SO group [P = .594]) and diastolic BP (mean [±SD] changes were -4.26 ± 7.44 in the FO group [P = .007] and 1.30 ± 6.91 in the SO group [P = .344]), but marginally significant (P = .053) for malondialdehyde level (mean [±SD] changes were -1.29 ± 1.48 in the FO group [P < .001] and -0.52 ± 1.34 in the SO group [P = .52]). A significant decrease in weight was also found in both groups. However, waist circumference decreased significantly only in the FO group at the end of the study (P < .05).

CONCLUSION:

Our results indicated that dietary FO could be effective in amelioration of some symptoms of MetSyn and decrease BP and lipid peroxidation.

KEYWORDS:

Blood pressure; Flaxseed oil; Lipid peroxidation; Metabolic syndrome; Sunflower seed oil

 

Improved Insulin Sensitivity Appears to Remain for a Mean of Four Years Following Islet Cell Transplant for Type 1 Diabetes.

Rydzon B, Monson RS, Oberholzer J, Varady KA, Bellin MD, Danielson KK.

Diabetes Metab Res Rev. 2017 Dec 12. doi: 10.1002/dmrr.2972. [Epub ahead of print]

PMID: 29230944

Abstract

BACKGROUND:

Impaired insulin sensitivity (IS) predicts complications and mortality in type 1 diabetes (T1D). IS improves shortly after islet cell transplant for type 1 diabetes, yet long-term changes in IS, and associated factors such as patient characteristics, transplant factors, clinical management, and IS-related biomarkers are unknown.

METHODS:

Up to nine years (mean four) of longitudinal data were available on 22 adults (18 female) with T1D who received 1-3 transplants in Phase 1/2 or 3 clinical trials (2004-2014). Metabolic testing post-transplant estimated IS by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR; 111 observations) and the Simple Index of Insulin Sensitivity (SIis ; 95 observations).

RESULTS:

SIis significantly increased the first year post-transplant (p=0.02), then stabilized (p=0.39); HOMA-IR remained stable post-transplant (p=0.92). Adjusting for age and BMI, higher SIis was associated with lower HbA1c following transplant (p=0.03). Greater IS as measured by lower HOMA-IR and higher SIis was associated with lower fasting C-peptide (both p<0.04), and also with higher exenatide dose (both p<0.01). More islets transplanted was associated with higher SIis (p<0.0001). Lower leptin at transplant predicted lower HOMA-IR and higher SIis after transplant, and lower bone marker RANKL predicted lower HOMA-IR (all p<0.01).

CONCLUSIONS:

IS measured by SIis was improved several years following transplant, while IS measured by HOMA-IR did not worsen. Higher exenatide dose, more islets transplanted, and diet and exercise (lowering leptin and RANKL) may improve IS, which may enhance glycemic control and lower metabolic demand on transplanted islets. Long-term clamp studies are needed to confirm these results.

KEYWORDS:

exenatide; insulin sensitivity; islet cell transplantation; leptin; receptor activator of nuclear factor kappa-B ligand (RANKL); type 1 diabetes

 

Intermittent versus continuous feeding in critically ill adults.

Patel JJ, Rosenthal MD, Heyland DK.

Curr Opin Clin Nutr Metab Care. 2017 Dec 11. doi: 10.1097/MCO.0000000000000447. [Epub ahead of print]

PMID: 29232262

Abstract

PURPOSE OF REVIEW:

Early enteral nutrition is recommended in critically ill adult patients. The optimal method of administering enteral nutrition remains unknown. Continuous enteral nutrition administration in critically ill patients remains the most common practice worldwide; however, its practice has recently been called into question in favor of intermittent enteral nutrition administration, where volume is infused multiple times per day. This review will outline the key differences between continuous and intermittent enteral nutrition, describe the metabolic responses to continuous and intermittent enteral nutrition administration and outline recent studies comparing continuous with intermittent enteral nutrition administration on outcomes in critically ill adults.

RECENT FINDINGS:

In separate studies, healthy humans and critically ill patients receiving intermittent nutrition (infused over 3 h) had improved whole body protein balance from negative to positive. These studies did not have an isonitrogenous control group. A randomized controlled trial of intermittent bolus versus continuous enteral nutrition in healthy humans found that intermittent bolus feeding increased mesenteric arterial blood flow, increased insulin and peptide YY and reduced blood glucose concentration. A randomized controlled trial comparing intermittent bolus to continuous enteral nutrition in critically ill patients did not demonstrate clinically relevant differences in glycemic variability, insulin use or tube feeding volume or caloric intake between the two groups.

SUMMARY:

Studies in healthy humans suggest that intermittent nutrient administration, as opposed to continuous, improves whole body protein synthesis. Unfortunately, similarly designed studies are lacking for critically ill patients. Future studies evaluating the impact of intermittent versus continuous nutrition administration on critical care outcomes should take into account factors such as protein quantity, protein quality and delivery route (enteral and/or parenteral). Until further studies are conducted in critically ill patients, a recommendation for or against intermittent nutrition delivery cannot be made.

 

Predicting Trajectories of Functional Decline in 60- to 70-Year-Old People.

Jonkman NH, Del Panta V, Hoekstra T, Colpo M, van Schoor NM, Bandinelli S, Cattelani L, Helbostad JL, Vereijken B, Pijnappels M, Maier AB.

Gerontology. 2017 Dec 13. doi: 10.1159/000485135. [Epub ahead of print]

PMID: 29232671

https://www.karger.com/Article/FullText/485135

https://www.karger.com/Article/Pdf/485135

Abstract

BACKGROUND:

Early identification of people at risk of functional decline is essential for delivering targeted preventive interventions.

OBJECTIVE:

The aim of this study is to identify and predict trajectories of functional decline over 9 years in males and females aged 60-70 years.

METHODS:

We included 403 community-dwelling participants from the InCHIANTI study and 395 from the LASA study aged 60-70 years at baseline, of whom the majority reported no functional decline at baseline (median 0, interquartile range 0-1). Participants were included if they reported data on ≥2 measurements of functional ability during a 9-year follow-up. Functional ability was scored with 6 self-reported items on activities of daily living. We performed latent class growth analysis to identify trajectories of functional decline and applied multinomial regression models to develop prediction models of identified trajectories. Analyses were stratified for sex.

RESULTS:

Three distinct trajectories were identified: no/little decline (219 males, 241 females), intermediate decline (114 males, 158 females), and severe decline (36 males, 30 females). Higher gait speed showed decreased risk of functional limitations in males (intermediate limitations, odds ratio [OR] 0.74, 95% CI 0.57-0.97; severe limitations, OR 0.42, 95% CI 0.26-0.66). The final model in males further included the predictors fear of falling and alcohol intake (no/little decline, area under the receiver operating curve [AUC] 0.68, 95% CI 0.62-0.73; intermediate decline, AUC 0.63, 95% CI 0.56-0.69; severe decline, AUC 0.79, 95% CI 0.71-0.87). In females, higher gait speed showed a decreased risk of intermediate limitations (OR 0.51, 95% CI 0.38-0.68) and severe limitations (OR 0.18, 95% CI 0.07-0.44). Other predictors in females were age, living alone, economic satisfaction, balance, physical activity, BMI, and cardiovascular disease (no/little decline, AUC 0.80, 95% CI 0.75-0.85; intermediate decline, AUC 0.74, 95% CI 0.69-0.79; severe decline, AUC 0.95, 95% CI 0.91-0.99).

CONCLUSION:

Already in people aged 60-70 years, 3 distinct trajectories of functional decline were identified in these cohorts over a 9-year follow-up. Predictors of trajectories differed between males and females, except for gait speed. Identification of people at risk is the basis for targeting interventions.

KEYWORDS:

Decision-making; Disability; Middle age; Physical performance; Prevention; Prognosis; Successful aging

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Identification and characterization of two functional variants in the human longevity gene FOXO3.

Flachsbart F, Dose J, Gentschew L, Geismann C, Caliebe A, Knecht C, Nygaard M, Badarinarayan N, ElSharawy A, May S, Luzius A, Torres GG, Jentzsch M, Forster M, Häesler R, Pallauf K, Lieb W, Derbois C, Galan P, Drichel D, Arlt A, Till A, Krause-Kyora B, Rimbach G, Blanché H, Deleuze JF, Christiansen L, Christensen K, Nothnagel M, Rosenstiel P, Schreiber S, Franke A, Sebens S, Nebel A.

Nat Commun. 2017 Dec 12;8(1):2063. doi: 10.1038/s41467-017-02183-y.

PMID: 29234056

https://www.nature.com/articles/s41467-017-02183-y

Abstract

FOXO3 is consistently annotated as a human longevity gene. However, functional variants and underlying mechanisms for the association remain unknown. Here, we perform resequencing of the FOXO3 locus and single-nucleotide variant (SNV) genotyping in three European populations. We find two FOXO3 SNVs, rs12206094 and rs4946935, to be most significantly associated with longevity and further characterize them functionally. We experimentally validate the in silico predicted allele-dependent binding of transcription factors (CTCF, SRF) to the SNVs. Specifically, in luciferase reporter assays, the longevity alleles of both variants show considerable enhancer activities that are reversed by IGF-1 treatment. An eQTL database search reveals that the alleles are also associated with higher FOXO3 mRNA expression in various human tissues, which is in line with observations in long-lived model organisms. In summary, we present experimental evidence for a functional link between common intronic variants in FOXO3 and human longevity.

 

Effects of Weight Loss on Advanced Glycation End Products in Subjects with and without Diabetes: A Preliminary Report.

Deo P, Keogh JB, Price NJ, Clifton PM.

Int J Environ Res Public Health. 2017 Dec 11;14(12). pii: E1553. doi: 10.3390/ijerph14121553.

PMID: 29232895

Abstract

Advanced glycation end-products (AGEs) are formed endogenously as a normal ageing process and during food processing. High levels of AGEs have been implicated in the development of both macrovascular disease and microvascular disease. The purpose of this secondary analysis was to determine whether a major AGE species, Nε-carboxymethyllysine (CML), was reduced after weight loss. CML values decreased by 17% after weight loss. Participants with diabetes and pre-diabetes had a lower CML values at baseline and a smaller change in CML than overweight participants without diabetes. We conclude that, in addition to the known health benefits, weight loss may reduce AGEs. Randomized studies of the effect of weight loss on AGE in people with and without type 2 diabetes are needed to confirm these results.

KEYWORDS:

Nε-carboxymethyllysine; advanced glycation end-products; weight loss

 

Dietary patterns and risk of recurrence and progression in non-muscle-invasive bladder cancer.

Westhoff E, Wu X, Kiemeney LA, Lerner SP, Ye Y, Huang M, Dinney CP, Vrieling A, Tu H.

Int J Cancer. 2017 Dec 13. doi: 10.1002/ijc.31214. [Epub ahead of print]

PMID: 29235103

Abstract

The association of dietary factors with urinary bladder cancer prognosis has scarcely been investigated, and results of studies conducted to date are inconsistent. We investigated whether empirically derived dietary patterns are associated with risks of recurrence and progression in non-muscle invasive bladder cancer patients. Data from 595 newly diagnosed non-muscle-invasive bladder cancer patients from an ongoing prospective cohort study were used to derive dietary patterns using exploratory factor analysis. Factor scores were calculated and then categorized in sex-specific tertiles. Multivariable adjusted proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals for the associations between tertiles of adherence to the dietary patterns and risks of recurrence and progression. We identified four dietary patterns: "fruits and vegetables", "Western", "low-fat", and "Tex-Mex". Patients in the highest tertile of adherence to the Western pattern experienced a 1.48 times higher risk of recurrence (95% CI 1.06-2.06) compared to patients in the lowest tertile. No statistically significant associations of a Western diet with risk of progression, or of the other dietary patterns with risk of recurrence and progression were found. Overall, we found that adherence to a Western diet was associated with a higher risk of recurrence but further studies are needed to confirm our findings.

KEYWORDS:

Diet; Factor analysis; Prognosis; Urinary bladder cancer

 

Effect of dietary habits on the risk of metabolic syndrome: Yazd Healthy Heart Project.

Sarebanhassanabadi M, Mirhosseini SJ, Mirzaei M, Namayandeh SM, Soltani MH, Pakseresht M, Pedarzadeh A, Baramesipour Z, Faraji R, Salehi-Abargouei A.

Public Health Nutr. 2017 Dec 13:1-8. doi: 10.1017/S1368980017003627. [Epub ahead of print]

PMID: 29233205

Abstract

OBJECTIVE:

Metabolic syndrome (MetS) refers to a group of risk factors that increase the risk of cardiovascular mortality and morbidity. Dietary habits are among the most important risk factors for MetS. The current study aimed at assessing the effect of dietary habits on the risk of MetS in a 10-year follow-up study in central Iran.

DESIGN:

Cohort study.

SETTING:

Yazd, Iran.

SUBJECTS:

Participants aged 20-74 years without any history of MetS, who were originally recruited for Yazd Healthy Heart Project (YHHP) during 2005-2006, were revisited during 2015-2016. At phase I of YHHP, demographic data, anthropometric measurements, five components of MetS, biochemical tests and dietary habits were evaluated; and the same data were collected in phase II.

RESULTS:

A total of 1092 participants were eligible to be included in the present study. After follow-up, the 10-year cumulative incidence of MetS was 56·1 %. After adjustment for potential confounders, increased risk of MetS (hazard ratio; 95 % CI) was found in those who did not try to control their body weight (1·57; 1·06, 2·35), did not usually eat salad (1·91; 1·22, 3·00) and added salt to their food (1·57, 1·06, 2·33). These associations were stronger in men than in the total population after subgroup analysis, but were not present in women.

CONCLUSIONS:

Dietary habits affect the risk of MetS in the Iranian population. Lifestyle interventions are needed to improve dietary habits to reduce the risk of MetS. Future studies are highly recommended to confirm our results in other populations.

KEYWORDS:

Cohort study; Dietary habits; Incidence; Metabolic syndrome

 

High blood glucose levels are associated with higher risk of colon cancer in men: a cohort study.

Vulcan A, Manjer J, Ohlsson B.

BMC Cancer. 2017 Dec 12;17(1):842. doi: 10.1186/s12885-017-3874-4.

PMID: 29233100

https://link.springer.com/article/10.1186/s12885-017-3874-4/fulltext.html

https://link.springer.com/content/pdf/10.1186%2Fs12885-017-3874-4.pdf

Abstract

BACKGROUND:

High levels of blood glucose are thought to be associated with colorectal cancer (CRC) and hyperinsulinemia, an interstage in the development of CRC. The purpose of this study was to examine associations between incident CRC and blood glucose; plasma insulin; and the homeostasis model assessment for insulin resistance (HOMA2-IR), respectively, and to determine whether these associations were dependent on sex and cancer site.

METHODS:

The Malmö Diet and Cancer cardiovascular cohort comprises 6103 individuals. During 81,781 person-years of follow-up, 145 cases of CRC were identified. The hazard ratio of measured blood glucose and plasma insulin and calculated HOMA2-IR were estimated with Cox proportional hazard regression.

RESULTS:

An association was found between high levels of blood glucose and risk of CRC (HR: 1.72 for the highest compared with the lowest quartile; 95% CI: 1.05, 2.84; ptrend = 0.044), and colon cancer (HR: 1.70 for the highest compared with the lowest quartile; 95% CI: 0.87, 3.33; ptrend = 0.032). In men, an association was found between blood glucose and CRC (HR: 2.80 for the highest compared with the lowest quartile; 95% CI: 1.37, 5.70; ptrend = 0.001), and colon cancer (HR: 4.48 for the highest compared with the lowest quartile; 95% CI: 1.27, 15.84; ptrend = 0.007), but this was not found in women. No associations between plasma insulin, or HOMA2-IR, and CRC, were found.

CONCLUSION:

High levels of blood glucose in men are associated with risk of colon cancer. The findings contribute to facilitating to identify those most in need of prevention and screening.

KEYWORDS:

Blood glucose; Colorectal cancer (CRC); Homeostasis model assessment of insulin resistance (HOMA2-IR); Malmö diet and cancer study; Plasma insulin; Sex

 

Anthropometric measurements and survival after a prostate cancer diagnosis.

Farris MS, Courneya KS, Kopciuk KA, McGregor SE, Friedenreich CM.

Br J Cancer. 2017 Dec 12. doi: 10.1038/bjc.2017.440. [Epub ahead of print]

PMID: 29235565

Abstract

BACKGROUND:

Evidence regarding the role of anthropometrics in prostate cancer survival is inconsistent. We examined the associations between anthropometric measures and survival outcomes.

METHODS:

Men diagnosed with prostate cancer (n=987) were recruited into a population-based case-control study between 1997 and 2000 then a prospective cohort study between 2000 and 2002 where anthropometric measurements (weight, height, body mass index, waist circumference, waist-hip ratio) were taken and participants were followed up to 19 years for survival outcomes. Cox proportional hazards were used to examine these associations.

RESULTS:

Survival analyses suggested no clear pattern of associations between post-diagnosis anthropometric measurements and all-cause mortality, prostate-specific mortality, first recurrence/progression or new primary cancer.

CONCLUSIONS:

We did not find a significant trend relating anthropometrics to survival outcomes after prostate cancer diagnosis. Continued assessment of objective measurements of body composition over the life-course is warranted to determine true associations between anthropometrics and survival after prostate cancer.

 

Heart Rate Variability and Cognitive Function In Middle-Age Adults: The Coronary Artery Risk Development in Young Adults.

Zeki Al Hazzouri A, Elfassy T, Carnethon MR, Lloyd-Jones DM, Yaffe K.

Am J Hypertens. 2017 Dec 8;31(1):27-34. doi: 10.1093/ajh/hpx125.

PMID: 28985245

Abstract

BACKGROUND:

Low heart rate variability (HRV), a marker of cardiac autonomic dysfunction, has been associated with major risk factors of cognitive impairment. Yet, the direct association of HRV with cognitive function remains relatively unexplored, particularly in midlife.

METHODS:

In 2005, 2 measures of short-term HRV, the SD of normal-to-normal intervals (SDNN) and the root mean square of successive differences (RMSSD), were calculated for participants of the Coronary Artery Risk Development in Young Adults study, and then categorized into quartiles. Five years later, 3 cognitive tests were administered for verbal memory ("Rey Auditory-Verbal Learning Test", RAVLT, range 0-15), processing speed ("Digit Symbol Substitution Test", DSST, range 0-133), and executive function ("Stroop interference").

RESULTS:

Two thousand one hundred and eighteen participants (57.7% female, 42.2% Black) with a mean baseline age of 45.3 years were included in this analysis. In demographic-adjusted models, compared to participants with quartile 1 SDNN (lowest quartile), participants in the upper quartiles of SDNN scored better on the DSST (quartile 4: β = 1.83 points better, P = 0.03; and quartile 3: β = 1.95 points better, P = 0.03) and on the stroop (quartile 3: β = 1.19 points better, P < 0.05; and quartile2: β = 1.44 points better, P = 0.02). After adjusting for behavioral and cardiovascular risk factors, higher quartile SDNN remained significantly associated with better stroop score (quartile 3: β = 1.21 points better, P = 0.04; and quartile 2: β = 1.72 points better, P < 0.01) but not with DSST. There was no association between quartile of RMSSD and cognitive function, from fully adjusted models.

CONCLUSIONS:

Our findings suggest that higher quartile SDDN is associated with better executive function in midlife, above, and beyond cardiovascular risk factors.

KEYWORDS:

Aging; autonomic function; blood pressure; cognition; epidemiology; heart rate variability; hypertension

 

The Scientist » News & Opinion » Daily News

Can Young Stem Cells Make Older People Stronger?

Small trials using younger donors and elderly recipients hint that mesenchymal stem cell transfers might reduce frailty.

By Shawna Williams | December 11, 2017

>>>>>>>>>>>>>>>>>>>>>>

Stem Cell Transplantation for Frailty.

Le Couteur DG, Anderson RM, Newman AB, de Cabo R.

J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1503-1504. doi: 10.1093/gerona/glx158. No abstract available.

PMID: 29028259

>>>>>>>>>>>>>>>>>

Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Tompkins BA, DiFede DL, Khan A, Landin AM, Schulman IH, Pujol MV, Heldman AW, Miki R, Goldschmidt-Clermont PJ, Goldstein BJ, Mushtaq M, Levis-Dusseau S, Byrnes JJ, Lowery M, Natsumeda M, Delgado C, Saltzman R, Vidro-Casiano M, Da Fonseca M, Golpanian S, Premer C, Medina A, Valasaki K, Florea V, Anderson E, El-Khorazaty J, Mendizabal A, Green G, Oliva AA, Hare JM.

J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1513-1522. doi: 10.1093/gerona/glx137.

PMID: 28977399

Abstract

BACKGROUND:

Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal stem cells (allo-hMSCs) exert immunomodulatory effects and promote tissue repair.

METHODS:

This is a randomized, double-blinded, dose-finding study of intravenous allo-hMSCs (100 or 200-million [M]) vs placebo delivered to patients (n = 30, mean age 75.5 ± 7.3) with frailty. The primary endpoint was incidence of treatment-emergent serious adverse events (TE-SAEs) at 1-month postinfusion. Secondary endpoints included physical performance, patient-reported outcomes, and immune markers of frailty measured at 6 months postinfusion.

RESULTS:

No therapy-related TE-SAEs occurred at 1 month. Physical performance improved preferentially in the 100M-group; immunologic improvement occurred in both the 100M- and 200M-groups. The 6-minute walk test, short physical performance exam, and forced expiratory volume in 1 second improved in the 100M-group (p = .01), not in the 200M- or placebo groups. The female sexual quality of life questionnaire improved in the 100M-group (p = .03). Serum TNF-α levels decreased in the 100M-group (p = .03). B cell intracellular TNF-α improved in both the 100M- (p < .0001) and 200M-groups (p = .002) as well as between groups compared to placebo (p = .003 and p = .039, respectively). Early and late activated T-cells were also reduced by MSC therapy.

CONCLUSION:

Intravenous allo-hMSCs were safe in individuals with aging frailty. Treated groups had remarkable improvements in physical performance measures and inflammatory biomarkers, both of which characterize the frailty syndrome. Given the excellent safety and efficacy profiles demonstrated in this study, larger clinical trials are warranted to establish the efficacy of hMSCs in this multisystem disorder.

KEYWORDS:

Immunomodulation; Regenerative medicine; Tumor necrosis factor-α

>>>>>>>>>>>>>>>>>>>>>>>>

Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty.

Golpanian S, DiFede DL, Khan A, Schulman IH, Landin AM, Tompkins BA, Heldman AW, Miki R, Goldstein BJ, Mushtaq M, Levis-Dusseau S, Byrnes JJ, Lowery M, Natsumeda M, Delgado C, Saltzman R, Vidro-Casiano M, Pujol MV, Da Fonseca M, Oliva AA Jr, Green G, Premer C, Medina A, Valasaki K, Florea V, Anderson E, El-Khorazaty J, Mendizabal A, Goldschmidt-Clermont PJ, Hare JM.

J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1505-1512. doi: 10.1093/gerona/glx056.

PMID: 28444181

Abstract

BACKGROUND:

Impaired endogenous stem cell repair capacity is hypothesized to be a biologic basis of frailty. Therapies that restore regenerative capacity may therefore be beneficial. This Phase 1 study evaluated the safety and potential efficacy of intravenous, allogeneic, human mesenchymal stem cell (allo-hMSC)-based therapy in patients with aging frailty.

METHODS:

In this nonrandomized, dose-escalation study, patients received a single intravenous infusion of allo-hMSCs: 20-million (n = 5), 100-million (n = 5), or 200-million cells (n = 5). The primary endpoint was incidence of any treatment-emergent serious adverse events measured at 1 month postinfusion. The secondary endpoints were functional efficacy domains and inflammatory biomarkers, measured at 3 and 6 months, respectively.

RESULTS:

There were no treatment-emergent serious adverse events at 1-month postinfusion or significant donor-specific immune reactions during the first 6 months. There was one death at 258 days postinfusion in the 200-million group. In all treatment groups, 6-minute walk distance increased at 3 months (p = .02) and 6 months (p = .001) and TNF-α levels decreased at 6 months (p < .0001). Overall, the 100-million dose showed the best improvement in all parameters, with the exception of TNF-α, which showed an improvement in both the 100- and 200-million groups (p = .0001 and p = .0001, respectively). The 100-million cell-dose group also showed significant improvements in the physical component of the SF-36 quality of life assessment at all time points relative to baseline.

CONCLUSIONS:

Allo-hMSCs are safe and immunologically tolerated in aging frailty patients. Improvements in functional and immunologic status suggest that ongoing clinical development of cell-based therapy is warranted for frailty.

KEYWORDS:

Cell-based therapy; Inflammation; Physical function; Regenerative medicine

Edited by AlPater

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Risk factors for first hospitalization due to meniscal lesions - a population-based cohort study with 30 years of follow-up.

Kontio T, Heliövaara M, Rissanen H, Knekt P, Aromaa A, Solovieva S.

BMC Musculoskelet Disord. 2017 Dec 13;18(1):528. doi: 10.1186/s12891-017-1886-5.

PMID: 29237499

https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-017-1886-5

https://bmcmusculoskeletdisord.biomedcentral.com/track/pdf/10.1186/s12891-017-1886-5?site=bmcmusculoskeletdisord.biomedcentral.com

Abstract

BACKGROUND:

Meniscal lesions are among the most common injuries of the knee, yet limited epidemiologic data is available on their risk factors. We investigated the association of lifestyle factors and physical strenuousness of work on knee injuries with a focus on meniscal lesions.

METHODS:

We examined a nationally representative sample of persons aged 30 to 59 years, who participated in a comprehensive health examination (the Mini-Finland Health Survey). Subjects without any injury or osteoarthritis in the knee joint at baseline (n = 4713) were subsequently followed via the National Hospital Discharge Register up to 30 years.

RESULTS:

During the follow-up, 338 knee injuries were identified of which 224 were meniscal lesions. Obesity and regular leisure time physical exercise were associated with an increased risk of first hospitalization due to meniscal lesions (hazard ratio (HR) 1.62 and 95% confidence interval (CI) 1.06-2.48 and 1.53, 95% CI 1.05-2.23, respectively). The types of sports predicting the highest risk of meniscal lesions were ballgames, gymnastics and jogging. Physical strenuousness of work did not predict meniscal lesion. The hazard of other knee injury was increased among those reporting irregular or regular physical exercise at baseline (HR 1.64, 95% CI 1.03-2.64 and 1.88 CI 1.05-2.36, respectively). Smoking or alcohol intake were not associated with knee injuries.

CONCLUSIONS:

Better safety measures in high-risk sports and weight control would likely improve the prevention of meniscal lesions in populations.

KEYWORDS:

Epidemiology; Knee; Meniscal lesion; Meniscal tear; Obesity; Risk factors

 

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: US Preventive Services Task Force Recommendation Statement.

US Preventive Services Task Force, Grossman DC, Curry SJ, Owens DK, Barry MJ, Davidson KW, Doubeni CA, Epling JW Jr, Kemper AR, Krist AH, Kurth AE, Landefeld CS, Mangione CM, Phipps MG, Silverstein M, Simon MA, Tseng CW.

JAMA. 2017 Dec 12;318(22):2224-2233. doi: 10.1001/jama.2017.18261.

PMID: 29234814

free access has active quiz has audio JAMA. 2017;318(22):2224-2233. doi:10.1001/jama.2017.18261

https://jamanetwork.com/journals/jama/fullarticle/2665782

This Recommendation Statement from the US Preventive Services Task Force recommends against use of hormone therapy for primary prevention of chronic conditions in postmenopausal women (D recommendation).

>>>>>>>>>>>>>>>>>

Abstract

IMPORTANCE:

Menopause occurs at a median age of 51.3 years, and the average US woman who reaches menopause is expected to live another 30 years. The prevalence and incidence of most chronic conditions, such as coronary heart disease, dementia, stroke, fractures, and breast cancer, increase with age; however, the excess risk for these conditions that can be attributed to menopause alone is uncertain. Since the publication of findings from the Women's Health Initiative that hormone therapy use is associated with serious adverse health effects in postmenopausal women, use of menopausal hormone therapy has declined.

OBJECTIVE:

To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on the use of menopausal hormone therapy for the primary prevention of chronic conditions.

EVIDENCE REVIEW:

The USPSTF reviewed the evidence on the benefits and harms of systemic (ie, oral or transdermal) hormone therapy for the prevention of chronic conditions in postmenopausal women and whether outcomes vary among women in different subgroups or by timing of intervention after menopause. The review did not address hormone therapy for preventing or treating menopausal symptoms.

FINDINGS:

Although the use of hormone therapy to prevent chronic conditions in postmenopausal women is associated with some benefits, there are also well-documented harms. The USPSTF determined that the magnitude of both the benefits and the harms of hormone therapy in postmenopausal women is small to moderate. Therefore, the USPSTF concluded with moderate certainty that combined estrogen and progestin has no net benefit for the primary prevention of chronic conditions for most postmenopausal women with an intact uterus and that estrogen alone has no net benefit for the primary prevention of chronic conditions for most postmenopausal women who have had a hysterectomy.

CONCLUSIONS AND RECOMMENDATION:

The USPSTF recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal women. (D recommendation) The USPSTF recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal women who have had a hysterectomy. (D recommendation).

>>>>>>>>>>>>>>>>>>>

Comment in

Menopausal Hormone Therapy for Primary Prevention of Chronic Disease.

Lewis CE, Wellons MF.

JAMA. 2017 Dec 12;318(22):2187-2189. doi: 10.1001/jama.2017.16974. No abstract available.

PMID: 29234792

https://jamanetwork.com/journals/jama/fullarticle/2665758

>>>>>>>>>>>>>>>>>

Editorial

Menopausal Hormone Therapy for the Primary Prevention of Chronic Conditions: Unfulfilled Expectations.

Wenger NK.

JAMA Cardiol. 2017 Dec 12. doi: 10.1001/jamacardio.2017.4575. [Epub ahead of print] No abstract available.

PMID: 29234780

https://jamanetwork.com/journals/jamacardiology/fullarticle/2665996

>>>>>>>>>>>>>>>>>>>>>>>>>>

Menopausal Hormone Therapy for Primary Prevention of Chronic Disease.

Lewis CE, Wellons MF.

JAMA. 2017 Dec 12;318(22):2187-2189. doi: 10.1001/jama.2017.16974. No abstract available.

PMID: 29234792

https://jamanetwork.com/journals/jama/fullarticle/2665758

>>>>>>>>>>>>>>>>>>>>

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Gartlehner G, Patel SV, Feltner C, Weber RP, Long R, Mullican K, Boland E, Lux L, Viswanathan M.

JAMA. 2017 Dec 12;318(22):2234-2249. doi: 10.1001/jama.2017.16952.

PMID: 29234813

free access JAMA. 2017;318(22):2234-2249. doi:10.1001/jama.2017.16952

https://jamanetwork.com/journals/jama/fullarticle/2665781

This systematic review to support the 2017 update of the US Preventive Services Task Force Recommendation Statement on use of hormone therapy summarizes published evidence on the benefits and harms of hormone therapy for primary prevention of chronic conditions in postmenopausal women.

Abstract

IMPORTANCE:

Postmenopausal status coincides with increased risks for chronic conditions such as heart disease, osteoporosis, cognitive impairment, or some types of cancers. Previously, hormone therapy was used for the primary prevention of these chronic conditions.

OBJECTIVE:

To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions.

DATA SOURCES:

MEDLINE, Cochrane Library, EMBASE, and trial registries from June 1, 2011, through August 1, 2016. Surveillance for new evidence in targeted publications was conducted through July 1, 2017.

STUDY SELECTION:

English-language randomized clinical trials reporting health outcomes.

DATA EXTRACTION AND SYNTHESIS:

Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available.

MAIN OUTCOMES AND MEASURES:

Beneficial or harmful changes in risks for various chronic conditions.

RESULTS:

Eighteen trials (n = 40 058; range, 142-16 608; mean age, 53-79 years) were included. Women using estrogen-only therapy compared with placebo had significantly lower risks, per 10 000 person-years, for diabetes (-19 cases [95% CI, -34 to -3]) and fractures (-53 cases [95% CI, -69 to -39]). Risks were statistically significantly increased, per 10 000 person-years, for gallbladder disease (30 more cases [95% CI, 16 to 48]), stroke (11 more cases [95% CI, 2 to 23]), venous thromboembolism (11 more cases [95% CI, 3 to 22]), and urinary incontinence (1261 more cases [95% CI, 880 to 1689]). Women using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 person-years, for colorectal cancer (-6 cases [95% CI, -9 to -1]), diabetes (-14 cases [95% CI, -24 to -3), and fractures (-44 cases [95% CI, -71 to -13). Risks, per 10 000 person-years, were significantly increased for invasive breast cancer (9 more cases [95% CI, 1 to 19]), probable dementia (22 more cases [95% CI, 4 to 53]), gallbladder disease (21 more cases [95% CI, 10 to 34]), stroke (9 more cases [95% CI, 2 to 19]), urinary incontinence (876 more cases [95% CI, 606 to 1168]), and venous thromboembolism (21 more cases [95% CI, 12 to 33]).

CONCLUSIONS AND RELEVANCE:

Hormone therapy for the primary prevention of chronic conditions in menopausal women is associated with some beneficial effects but also with a substantial increase of risks for harms. The available evidence regarding benefits and harms of early initiation of hormone therapy is inconclusive.

 

Can Exercise Prevent Knee Osteoarthritis?

Abbasi J.

JAMA. 2017 Dec 12;318(22):2169-2171. doi: 10.1001/jama.2017.16144. No abstract available.

PMID: 29167894

free access JAMA. 2017;318(22):2169-2171. doi:10.1001/jama.2017.16144

https://jamanetwork.com/journals/jama/fullarticle/2664339

This Medical News article discusses whether sedentary lifestyles contribute to this increasingly prevalent degenerative joint disease.

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Knee osteoarthritis has doubled in prevalence since the mid-20th century.

Wallace IJ, Worthington S, Felson DT, Jurmain RD, Wren KT, Maijanen H, Woods RJ, Lieberman DE.

Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):9332-9336. doi: 10.1073/pnas.1703856114. Epub 2017 Aug 14.

PMID: 28808025 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584421/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584421/pdf/pnas.201703856.pdf

Abstract

Knee osteoarthritis (OA) is believed to be highly prevalent today because of recent increases in life expectancy and body mass index (BMI), but this assumption has not been tested using long-term historical or evolutionary data. We analyzed long-term trends in knee OA prevalence in the United States using cadaver-derived skeletons of people aged ≥50 y whose BMI at death was documented and who lived during the early industrial era (1800s to early 1900s; n = 1,581) and the modern postindustrial era (late 1900s to early 2000s; n = 819). Knee OA among individuals estimated to be ≥50 y old was also assessed in archeologically derived skeletons of prehistoric hunter-gatherers and early farmers (6000-300 B.P.; n = 176). OA was diagnosed based on the presence of eburnation (polish from bone-on-bone contact). Overall, knee OA prevalence was found to be 16% among the postindustrial sample but only 6% and 8% among the early industrial and prehistoric samples, respectively. After controlling for age, BMI, and other variables, knee OA prevalence was 2.1-fold higher (95% confidence interval, 1.5-3.1) in the postindustrial sample than in the early industrial sample. Our results indicate that increases in longevity and BMI are insufficient to explain the approximate doubling of knee OA prevalence that has occurred in the United States since the mid-20th century. Knee OA is thus more preventable than is commonly assumed, but prevention will require research on additional independent risk factors that either arose or have become amplified in the postindustrial era.

KEYWORDS:

aging; arthritis; evolutionary medicine; mismatch disease; obesity

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Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults.

NCD Risk Factor Collaboration (NCD-RisC).

Lancet. 2017 Oct 10. pii: S0140-6736(17)32129-3. doi: 10.1016/S0140-6736(17)32129-3. [Epub ahead of print]

PMID: 29029897 Free Article

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32129-3/fulltext

Abstract

BACKGROUND:

Underweight, overweight, and obesity in childhood and adolescence are associated with adverse health consequences throughout the life-course. Our aim was to estimate worldwide trends in mean body-mass index (BMI) and a comprehensive set of BMI categories that cover underweight to obesity in children and adolescents, and to compare trends with those of adults.

METHODS:

We pooled 2416 population-based studies with measurements of height and weight on 128·9 million participants aged 5 years and older, including 31·5 million aged 5-19 years. We used a Bayesian hierarchical model to estimate trends from 1975 to 2016 in 200 countries for mean BMI and for prevalence of BMI in the following categories for children and adolescents aged 5-19 years: more than 2 SD below the median of the WHO growth reference for children and adolescents (referred to as moderate and severe underweight hereafter), 2 SD to more than 1 SD below the median (mild underweight), 1 SD below the median to 1 SD above the median (healthy weight), more than 1 SD to 2 SD above the median (overweight but not obese), and more than 2 SD above the median (obesity).

FINDINGS:

Regional change in age-standardised mean BMI in girls from 1975 to 2016 ranged from virtually no change (-0·01 kg/m2 per decade; 95% credible interval -0·42 to 0·39, posterior probability [PP] of the observed decrease being a true decrease=0·5098) in eastern Europe to an increase of 1·00 kg/m2 per decade (0·69-1·35, PP>0·9999) in central Latin America and an increase of 0·95 kg/m2 per decade (0·64-1·25, PP>0·9999) in Polynesia and Micronesia. The range for boys was from a non-significant increase of 0·09 kg/m2 per decade (-0·33 to 0·49, PP=0·6926) in eastern Europe to an increase of 0·77 kg/m2 per decade (0·50-1·06, PP>0·9999) in Polynesia and Micronesia. Trends in mean BMI have recently flattened in northwestern Europe and the high-income English-speaking and Asia-Pacific regions for both sexes, southwestern Europe for boys, and central and Andean Latin America for girls. By contrast, the rise in BMI has accelerated in east and south Asia for both sexes, and southeast Asia for boys. Global age-standardised prevalence of obesity increased from 0·7% (0·4-1·2) in 1975 to 5·6% (4·8-6·5) in 2016 in girls, and from 0·9% (0·5-1·3) in 1975 to 7·8% (6·7-9·1) in 2016 in boys; the prevalence of moderate and severe underweight decreased from 9·2% (6·0-12·9) in 1975 to 8·4% (6·8-10·1) in 2016 in girls and from 14·8% (10·4-19·5) in 1975 to 12·4% (10·3-14·5) in 2016 in boys. Prevalence of moderate and severe underweight was highest in India, at 22·7% (16·7-29·6) among girls and 30·7% (23·5-38·0) among boys. Prevalence of obesity was more than 30% in girls in Nauru, the Cook Islands, and Palau; and boys in the Cook Islands, Nauru, Palau, Niue, and American Samoa in 2016. Prevalence of obesity was about 20% or more in several countries in Polynesia and Micronesia, the Middle East and north Africa, the Caribbean, and the USA. In 2016, 75 (44-117) million girls and 117 (70-178) million boys worldwide were moderately or severely underweight. In the same year, 50 (24-89) million girls and 74 (39-125) million boys worldwide were obese.

INTERPRETATION:

The rising trends in children's and adolescents' BMI have plateaued in many high-income countries, albeit at high levels, but have accelerated in parts of Asia, with trends no longer correlated with those of adults.

 

The effect of physical activity on mortality and cardiovascular disease in 130 000 people from 17 high-income, middle-income, and low-income countries: the PURE study.

Lear SA, Hu W, Rangarajan S, Gasevic D, Leong D, Iqbal R, Casanova A, Swaminathan S, Anjana RM, Kumar R, Rosengren A, Wei L, Yang W, Chuangshi W, Huaxing L, Nair S, Diaz R, Swidon H, Gupta R, Mohammadifard N, Lopez-Jaramillo P, Oguz A, Zatonska K, Seron P, Avezum A, Poirier P, Teo K, Yusuf S.

Lancet. 2017 Sep 21. pii: S0140-6736(17)31634-3. doi: 10.1016/S0140-6736(17)31634-3. [Epub ahead of print]

PMID: 28943267

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31634-3/fulltext

http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(17)31634-3.pdf

Abstract

BACKGROUND:

Physical activity has a protective effect against cardiovascular disease (CVD) in high-income countries, where physical activity is mainly recreational, but it is not known if this is also observed in lower-income countries, where physical activity is mainly non-recreational. We examined whether different amounts and types of physical activity are associated with lower mortality and CVD in countries at different economic levels.

METHODS:

In this prospective cohort study, we recruited participants from 17 countries (Canada, Sweden, United Arab Emirates, Argentina, Brazil, Chile, Poland, Turkey, Malaysia, South Africa, China, Colombia, Iran, Bangladesh, India, Pakistan, and Zimbabwe). Within each country, urban and rural areas in and around selected cities and towns were identified to reflect the geographical diversity. Within these communities, we invited individuals aged between 35 and 70 years who intended to live at their current address for at least another 4 years. Total physical activity was assessed using the International Physical Activity Questionnaire (IPQA). Participants with pre-existing CVD were excluded from the analyses. Mortality and CVD were recorded during a mean of 6·9 years of follow-up. Primary clinical outcomes during follow-up were mortality plus major CVD (CVD mortality, incident myocardial infarction, stroke, or heart failure), either as a composite or separately. The effects of physical activity on mortality and CVD were adjusted for sociodemographic factors and other risk factors taking into account household, community, and country clustering.

FINDINGS:

Between Jan 1, 2003, and Dec 31, 2010, 168 916 participants were enrolled, of whom 141 945 completed the IPAQ. Analyses were limited to the 130 843 participants without pre-existing CVD. Compared with low physical activity (<600 metabolic equivalents [MET] × minutes per week or <150 minutes per week of moderate intensity physical activity), moderate (600-3000 MET × minutes or 150-750 minutes per week) and high physical activity (>3000 MET × minutes or >750 minutes per week) were associated with graded reduction in mortality (hazard ratio 0·80, 95% CI 0·74-0·87 and 0·65, 0·60-0·71; p<0·0001 for trend), and major CVD (0·86, 0·78-0·93; p<0·001 for trend). Higher physical activity was associated with lower risk of CVD and mortality in high-income, middle-income, and low-income countries. The adjusted population attributable fraction for not meeting the physical activity guidelines was 8·0% for mortality and 4·6% for major CVD, and for not meeting high physical activity was 13·0% for mortality and 9·5% for major CVD. Both recreational and non-recreational physical activity were associated with benefits.

INTERPRETATION:

Higher recreational and non-recreational physical activity was associated with a lower risk of mortality and CVD events in individuals from low-income, middle-income, and high-income countries. Increasing physical activity is a simple, widely applicable, low cost global strategy that could reduce deaths and CVD in middle age.

 

Dietary intake of fish, n-3 polyunsaturated fatty acids and risk of hip fracture: A systematic review and meta-analysis on observational studies.

Sadeghi O, Djafarian K, Ghorabi S, Khodadost M, Nasiri M, Shab-Bidar S.

Crit Rev Food Sci Nutr. 2017 Dec 15:1-14. doi: 10.1080/10408398.2017.1405908. [Epub ahead of print]

PMID: 29244536

Abstract

Previous studies have shown that fish consumption and dietary intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) are associated with hip fracture; however, findings were conflicting. The present review aimed to summarize the current evidence on the association of fish consumption and dietary intake of n-3 PUFAs with hip fracture. The online databases of PubMed, ISI Web of Science, Scopus, ProQuest, Science Direct and Embase were searched until August 2017 for related publications using relevant keywords. To pool data, either a fixed-effects model or random-effects models were used. Cochran's Q tests were used to assess heterogeneity between studies. In total, 10 studies (7 prospective and 3 case-control studies) were included in this systematic review, and 9 studies with total sample size of 292657 participants were included in the meta-analysis. The age of participants was 20 years or older. Combining 8 effect sizes from 4 prospective studies and 2 case-control studies revealed a significant inverse association between fish consumption and risk of hip fracture (pooled effect size: 0.88, 95% CI: 0.79-0.98, P = 0.02). Although this relationship became non-significant in prospective studies, a significant inverse association was found in prospective studies with sample size of 10000 individuals or more, and studies that considered body mass index as a covariate. Furthermore, dietary intake of n-3 PUFAs was inversely associated with risk of hip fracture (pooled effect size: 0.89, 95% CI: 0.80-0.99, P = 0.02). Also, such relationship was seen after excluding one case-control study and combining effect sizes only from prospective studies (pooled effect size: 0.88, 95% CI: 0.80-0.98, P = 0.02). In conclusion, we found that fish consumption and dietary intake of n-3 PUFAs might have protective effects on bone health and decline the risk of hip fracture.

KEYWORDS:

Fatty acids; Fishes; Omega-3; hip fracture; meta-analysis

 

Vitamin D and Gestational Diabetes Mellitus: A Systematic Review Based on Data Free of Hawthorne Effect.

Zhang Y, Gong Y, Xue H, Xiong J, Cheng G.

BJOG. 2017 Dec 15. doi: 10.1111/1471-0528.15060. [Epub ahead of print]

PMID: 29244241

Abstract

BACKGROUND:

Gestational diabetes mellitus (GDM) is an increasingly prevalent disorder, associated with low blood vitamin D (VD) level.

OBJECTIVES:

To evaluate the relationship between VD and GDM.

SEARCH STRATEGY:

EMBASE, MEDLINE, Cochrane library and China Biology Medicine disc were searched till May 2017. The references of previous studies were screened.

SELECTION CRITERIA:

Observational studies on the relationship between VD and GDM free from Hawthorne effect and randomized controlled trials of VD supplementation during pregnancy for preventing or treating GDM were included.

DATA COLLECTION AND ANALYSIS:

Data and information of included articles were extracted by duplicate using piloted tables. Newcastle-Ottawa Scale and Cochrane Handbook were used for quality assessment. Random-effects models were used for meta-analyses. Heterogeneity tests, sensitive analysis, and analysis of publication bias were conducted.

MAIN RESULTS:

Eighty-seven observational studies and 25 randomized controlled trials involving 55859 and 2445 subjects respectively were included. Low blood VD level during pregnancy was associated with a higher risk of GDM (OR = 1.850, 95% CI: 1.471, 2.328). Blood VD level for subjects with GDM were lower than the controls. Blood VD level was associated with fasting plasma glucose (FPG) and HOMA-IR (r = -0.100 and -0.351), whereas the correlation between blood VD level and fasting insulin (FINS) might be concealed by publication bias. VD intervention during pregnancy could change blood level of VD, FINS, FPG, HOMA-IR, glutathione, C-reactive protein, and lipid.

CONCLUSIONS:

Low blood VD level could increase the risk of GDM, and VD supplementation during pregnancy could ameliorate the condition of GDM.

KEYWORDS:

Blood Glucose; Gestational Diabetes Mellitus; Insulin; Meta-analysis; Vitamin D

 

Association between berries intake and cardiovascular diseases risk factors: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials.

Luís Â, Domingues F, Pereira L.

Food Funct. 2017 Dec 15. doi: 10.1039/c7fo01551h. [Epub ahead of print] Review.

PMID: 29243749

http://www.rsc.org/suppdata/c7/fo/c7fo01551h/c7fo01551h1.pdf

Abstract

The main goal of this work was to clarify the effects of the consumption of berries on cardiovascular disease (CVD) risk factors by performing a systematic review according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement, followed by a meta-analysis and a trial sequential analysis (TSA) of randomized controlled trials (RCTs). The electronic search was conducted in PubMed, Scopus, SciELO, Web of Science and Cochrane Library between April and June 2016. To be included, RCTs had to report 1 or more of the following outcomes: total cholesterol (TC), HDL-cholesterol (HDL), LDL-cholesterol (LDL), triglycerides (TG), blood pressure (BP), C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM), intercellular adhesion molecule-1 (ICAM), glucose, insulin, apolipoprotein A-I (Apo A-I) or apolipoprotein B (Apo B). It was observed that the intake of berries reduces TC, LDL, TG, and BP while increasing the level of HDL, suggesting a beneficial effect on the control of CVDs' risk factors. Thus, the intake of berries as nutraceuticals or functional foods could be suggested for the prevention and control of CVDs.

 

Whey protein supplementation 2 hours after a lower protein breakfast restores plasma essential amino acid availability comparable to a higher protein breakfast in overweight adults.

Hudson JL, Paddon-Jones D, Campbell WW.

Nutr Res. 2017 Nov;47:90-97. doi: 10.1016/j.nutres.2017.09.007. Epub 2017 Oct 2.

PMID: 29241582

Abstract

Amino acids from meals peak in the plasma at ~180 minutes postprandial. Conversely, amino acids from rapidly digestible whey protein appear in the plasma within 15 minutes and peak at 60 minutes postprandial. Therefore, we hypothesized that consuming a 20-g whey protein snack 2 hours after a standard mixed-macronutrient, lower protein breakfast (10 g) would result in peak and composite postprandial plasma essential amino acid (EAA) responses that were not different from consuming a 30-g protein breakfast alone. Using a randomized, crossover design, 12 subjects (6 men, 6 women; age: 29 ± 1 y; BMI: 26.0 ± 1.0 kg/m2; mean ± SE) completed three 330-minute trials in which they consumed breakfasts containing (i) 10 g of protein (10-PRO, control), (ii) 30 g of protein (30-PRO), and (iii) 10 g of protein followed by 20 g of whey protein isolate 120 minutes later (10/20-PRO). For both 30-PRO and 10/20-PRO, EAA peaked 180 minutes after breakfast, with greater peak concentrations for 10/20-PRO than 30-PRO (Tukey adjusted, P < .0001). Essential amino acid positive incremental areas under the curve (iAUCpos) over 300 minutes were not different between 30-PRO and 10/20-PRO. Consuming a rapidly digested whey protein snack 2 hours after a slowly digested, lower protein breakfast resulted in a greater peak plasma EAA concentration but comparable plasma EAA availability than consuming a single higher protein breakfast.

KEYWORDS:

Dietary proteins; Dietary supplements; Postprandial plasma amino acids; Snacks; Whey proteins

 

Comfort Eating and All-Cause Mortality in the US Health and Retirement Study.

Cummings JR, Mason AE, Puterman E, Janet Tomiyama A.

Int J Behav Med. 2017 Dec 14. doi: 10.1007/s12529-017-9706-8. [Epub ahead of print]

PMID: 29243156

Abstract

PURPOSE:

Comfort eating is a prevalent behavior. Prior research shows that comfort eating is associated with reduced stress responses and increased metabolic risk across adolescence, young adulthood, and middle adulthood. The purpose of the current research was to test if comfort eating prospectively predicted all-cause mortality in older adulthood.

METHOD:

The US Health and Retirement Study is an ongoing, nationally representative, longitudinal study of older adults. The final sample for the present study (N = 1445) included participants randomly selected to report how often they comfort ate. Comfort eating data were collected in 2008 and all-cause mortality data were collected in 2014. Participants also reported how often they consumed high-fat/sugar food as well as their height and weight in 2008.

RESULTS:

For each 1-unit increase in comfort eating, the expected odds of all-cause mortality (n = 255 deceased) decreased by 14%, OR = 0.86, p = 0.048, 95% CI [0.74, 0.99]. This analysis statistically accounted for other predictors of mortality in the sample including age, biological sex, race, highest educational degree attained, moderate and vigorous exercise, smoking, and cumulative illness. High-fat/sugar intake did not mediate (or diminish) the association but body mass index did.

CONCLUSION:

Comfort eating-irrespective of consuming high-fat/sugar food-may be associated with reduced mortality in older adults because it may promote greater body mass, and greater body mass is associated with lower risk of mortality in nationally representative samples. Interventionists might consider both beneficial and detrimental aspects of comfort eating across the lifespan.

KEYWORDS:

Body mass index; High-fat/sugar food; Older adults; Stress

 

CK2 modulates adipocyte insulin-signaling and is up-regulated in human obesity.

Borgo C, Milan G, Favaretto F, Stasi F, Fabris R, Salizzato V, Cesaro L, Belligoli A, Sanna M, Foletto M, Prevedello L, Vindigni V, Bardini R, Donella-Deana A, Vettor R.

Sci Rep. 2017 Dec 14;7(1):17569. doi: 10.1038/s41598-017-17809-w.

PMID: 29242563

https://www.nature.com/articles/s41598-017-17809-w

Abstract

Insulin plays a major role in glucose metabolism and insulin-signaling defects are present in obesity and diabetes. CK2 is a pleiotropic protein kinase implicated in fundamental cellular pathways and abnormally elevated in tumors. Here we report that in human and murine adipocytes CK2-inhibition decreases the insulin-induced glucose-uptake by counteracting Akt-signaling and GLUT4-translocation to the plasma membrane. In mice CK2 acts on insulin-signaling in adipose tissue, liver and skeletal muscle and its acute inhibition impairs glucose tolerance. Notably, CK2 protein-level and activity are greatly up-regulated in white adipose tissue from ob/ob and db/db mice as well as from obese patients, regardless the severity of their insulin-resistance and the presence of pre-diabetes or overt type 2 diabetes. Weight loss obtained by both bariatric surgery or hypocaloric diet reverts CK2 hyper-activation to normal level. Our data suggest a central role of CK2 in insulin-sensitivity, glucose homeostasis and adipose tissue remodeling. CK2 up-regulation is identified as a hallmark of adipose tissue pathological expansion, suggesting a new potential therapeutic target for human obesity.

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Lifestyle, Diet, and Colorectal Cancer Risk According to (Epi)genetic Instability: Current Evidence and Future Directions of Molecular Pathological Epidemiology.

Hughes LAE, Simons CCJM, van den Brandt PA, van Engeland M, Weijenberg MP.

Curr Colorectal Cancer Rep. 2017;13(6):455-469. doi: 10.1007/s11888-017-0395-0. Epub 2017 Dec 2. Review.

PMID: 29249914

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725509/

Abstract

PURPOSE OF REVIEW:

In this review, we describe molecular pathological epidemiology (MPE) studies from around the world that have studied diet and/or lifestyle factors in relation to molecular markers of (epi)genetic pathways in colorectal cancer (CRC), and explore future perspectives in this realm of research. The main focus of this review is diet and lifestyle factors for which there is evidence for an association with CRC as identified by the World Cancer Research Fund reports. In addition, we review promising hypotheses, that warrant consideration in future studies.

RECENT FINDINGS:

Associations between molecular characteristics of CRC have been published in relation to smoking, alcohol consumption; body mass index (BMI); waist:hip ratio; adult attained height; physical activity; early life energy restriction; dietary acrylamide, fiber, fat, methyl donors, omega 3 fatty acids; meat, including total protein, processed meat, and heme iron; and fruit and vegetable intake.

SUMMARY:

MPE studies help identify where associations between diet, lifestyle, and CRC risk may otherwise be masked and also shed light on how timing of exposure can influence etiology. Sample size is often an issue, but this may be addressed in the future by pooling data.

KEYWORDS:

Colorectal cancer; Diet; Lifestyle; Molecular pathological epidemiology; Review

 

A prospective association between dietary folate intake and type 2 diabetes risk among Korean adults aged 40 years or older: the Korean Multi-Rural Communities Cohort (MRCohort) Study.

Hong SM, Woo HW, Kim MK, Kim SY, Lee YH, Shin DH, Shin MH, Chun BY, Choi BY.

Br J Nutr. 2017 Dec;118(12):1078-1088. doi: 10.1017/S0007114517003087. Epub 2017 Dec 4.

PMID: 29198189

Abstract

It has not been well established whether dietary folate intake reduces the risk of diabetes development. We aimed to clarify the prospective association between dietary folate intake and type 2 diabetes (T2D) risk among 7333 Korean adults aged 40 years or older who were included in the Multi-Rural Communities Cohort. Dietary folate intake was estimated from all 106 food items listed on a FFQ, not including folate intake from supplements. Two different measurements of dietary folate intake were used: the baseline consumption and the average consumption from baseline until just before the end of follow-up. The association between folate intake and T2D risk was determined through a modified Poisson regression model with a robust error estimator controlling for potential confounders. For 29 745 person years, 319 cases of diabetes were ascertained. In multivariable analyses, dietary folate intake was inversely associated with risk of T2D for women, not for men. For women, the incidence rate ratio of diabetes in the third tertile compared with the first tertile was 0·57 (95 % CI 0·38-0·87, P for trend=0·0085) in the baseline consumption model and 0·64 (95 % CI 0·43-0·95, P for trend=0·0244) in the average consumption model. These inverse associations was found in both normal fasting blood glucose group and impaired fasting glucose group among women. Among non-users of multinutrients and vitamin supplements, the significant inverse association remained. Thus, higher dietary intake of folate is prospectively associated with lower risk of diabetes for women.

KEYWORDS:

FBG fasting blood glucose; IFG impaired fasting glucose; IRR incidence rate ratio; NFG normal fasting glucose; T2D type 2 diabetes; Dietary folate intakes; Korea; Prospective cohort studies; Type 2 diabetes

 

The effects of diurnal Ramadan fasting on energy expenditure and substrate oxidation in healthy men.

Alsubheen SA, Ismail M, Baker A, Blair J, Adebayo A, Kelly L, Chandurkar V, Cheema S, Joanisse DR, Basset FA.

Br J Nutr. 2017 Dec;118(12):1023-1030. doi: 10.1017/S0007114517003221. Epub 2017 Dec 4.

PMID: 29198194

Abstract

The study aimed to examine the effects of diurnal Ramadan fasting (RF) on substrate oxidation, energy production, blood lipids and glucose as well as body composition. Nine healthy Muslim men (fasting (FAST) group) and eight healthy non-practicing men (control (CNT) group) were assessed pre- and post-RF. FAST were additionally assessed at days 10, 20 and 30 of RF in the morning and evening. Body composition was determined by hydrodensitometry, substrate oxidation and energy production by indirect calorimetry, blood metabolic profile by biochemical analyses and energy balance by activity tracker recordings and food log analyses. A significant group×time interaction revealed that chronic RF reduced body mass and adiposity in FAST, without changing lean mass, whereas CNT subjects remained unchanged. In parallel to these findings, a significant main diurnal effect (morning v. evening) of RF on substrate oxidation (a shift towards lipid oxidation) and blood metabolic profile (a decrease in glucose and an increase in total cholesterol and TAG levels, respectively) was observed, which did not vary over the course of the Ramadan. In conclusion, although RF induces diurnal metabolic adjustments (morning v. evening), no carryover effect was observed throughout RF despite the extended daily fasting period (18·0 (sd 0·3) h) and changes in body composition.

KEYWORDS:

BM body mass; CHO carbohydrate; CHOox carbohydrate oxidation; CNT control; EE energy expenditure; EP energy production; FAST fasting; FAT fat; FATox lipid oxidation; HR heart rate; IF intermittent fasting; MR metabolic rate; PRO protein; R1 10th day of RF; R2 20th day of RF; R3 30th day of RF; RF Ramadan fasting; VS vital signs; Body composition; Indirect calorimetry; Insulin; Lipid profiles; Ramadan; Substrate oxidation

 

Burden of hip fracture using disability-adjusted life-years: a pooled analysis of prospective cohorts in the CHANCES consortium.

Papadimitriou N, Tsilidis KK, Orfanos P, Benetou V, Ntzani EE, Soerjomataram I, Künn-Nelen A, Pettersson-Kymmer U, Eriksson S, Brenner H, Schöttker B, Saum KU, Holleczek B, Grodstein FD, Feskanich D, Orsini N, Wolk A, Bellavia A, Wilsgaard T, Jørgensen L, Boffetta P, Trichopoulos D, Trichopoulou A.

Lancet Public Health. 2017 May;2(5):e239-e246. doi: 10.1016/S2468-2667(17)30046-4. Epub 2017 Apr 11.

PMID: 29253489

Abstract

BACKGROUND:

No studies have estimated disability-adjusted life-years (DALYs) lost due to hip fractures using real-life follow-up cohort data. We aimed to quantify the burden of disease due to incident hip fracture using DALYs in prospective cohorts in the CHANCES consortium, and to calculate population attributable fractions based on DALYs for specific risk factors.

METHODS:

We used data from six cohorts of participants aged 50 years or older at recruitment to calculate DALYs. We applied disability weights proposed by the National Osteoporosis Foundation and did a series of sensitivity analyses to examine the robustness of DALY estimates. We calculated population attributable fractions for smoking, body-mass index (BMI), physical activity, alcohol intake, type 2 diabetes and parity, use of hormone replacement therapy, and oral contraceptives in women. We calculated summary risk estimates across cohorts with pooled analysis and random-effects meta-analysis methods.

FINDINGS:

223 880 men and women were followed up for a mean of 13 years (SD 6). 7724 (3·5%) participants developed an incident hip fracture, of whom 413 (5·3%) died as a result. 5964 DALYs (27 per 1000 individuals) were lost due to hip fractures, 1230 (20·6%) of which were in the group aged 75-79 years. 4150 (69·6%) DALYs were attributed to disability. Current smoking was the risk factor responsible for the greatest hip fracture burden (7·5%, 95% CI 5·2-9·7) followed by physical inactivity (5·5%, 2·1-8·5), history of diabetes (2·8%, 2·1-4·0), and low to average BMI (2·0%, 1·4-2·7), whereas low alcohol consumption (0·01-2·5 g per day) and high BMI had a protective effect.

INTERPRETATION:

Hip fracture can lead to a substantial loss of healthy life-years in elderly people. National public health policies should be strengthened to reduce hip fracture incidence and mortality. Primary prevention measures should be strengthened to prevent falls, and reduce smoking and a sedentary lifestyle.

 

Prospective study of restless legs syndrome and total and cardiovascular mortality among women.

Li Y, Li Y, Winkelman JW, Walters AS, Han J, Hu FB, Gao X.

Neurology. 2017 Dec 15. pii: 10.1212/WNL.0000000000004814. doi: 10.1212/WNL.0000000000004814. [Epub ahead of print]

PMID: 29247069

Abstract

OBJECTIVE:

We prospectively examined whether women with physician-diagnosed restless legs syndrome (RLS) had a higher risk of total and cardiovascular disease (CVD) mortality relative to those without RLS.

METHODS:

The current study included 57,417 women (mean age 67 years) from the Nurses' Health Study without cancer, renal failure, and CVD at baseline (2002). Main outcomes were total and CVD mortality. We used the Cox proportional hazards model to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and CVD-specific mortality based on RLS status, adjusting for age, presence of major chronic diseases, and other potential confounders.

RESULTS:

We documented 6,448 deaths during 10 years of follow-up. We did not observe a significant association between presence of physician-diagnosed RLS and high risk of total mortality (adjusted HR 1.15, 95% CI 0.98-1.34). When cause-specific mortality was studied, participants with RLS had a significantly higher risk of CVD mortality (adjusted HR 1.43, 95% CI 1.02-2.00) relative to those without RLS after adjustment for potential confounders. Longer duration of RLS diagnosis was significantly associated with a higher risk of CVD mortality (p for trend = 0.04). Excluding participants with common RLS comorbidities strengthened the association between RLS and total (adjusted HR 1.43, 95% CI 1.03-1.97) and CVD mortality (adjusted HR 2.27, 95% CI 1.21-4.28). However, we did not find a significant association between RLS and mortality due to cancer and other causes.

CONCLUSIONS:

Women with RLS had a higher CVD mortality rate, which may not be fully explained by common co-occurring disorders of RLS.

 

[The second below paper is pdf-availed.]

A dark side to omega-3 fatty acids.

Yanagida K, Hla T.

Nature. 2017 Dec 14;552(7684):180-181. doi: 10.1038/d41586-017-07678-8. No abstract available.

PMID: 29239390

https://www.nature.com/articles/d41586-017-07678-8

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Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy.

Hu J, Dziumbla S, Lin J, Bibli SI, Zukunft S, de Mos J, Awwad K, Frömel T, Jungmann A, Devraj K, Cheng Z, Wang L, Fauser S, Eberhart CG, Sodhi A, Hammock BD, Liebner S, Müller OJ, Glaubitz C, Hammes HP, Popp R, Fleming I.

Nature. 2017 Dec 14;552(7684):248-252. doi: 10.1038/nature25013. Epub 2017 Dec 6.

PMID: 29211719

Abstract

Diabetic retinopathy is an important cause of blindness in adults, and is characterized by progressive loss of vascular cells and slow dissolution of inter-vascular junctions, which result in vascular leakage and retinal oedema. Later stages of the disease are characterized by inflammatory cell infiltration, tissue destruction and neovascularization. Here we identify soluble epoxide hydrolase (sEH) as a key enzyme that initiates pericyte loss and breakdown of endothelial barrier function by generating the diol 19,20-dihydroxydocosapentaenoic acid, derived from docosahexaenoic acid. The expression of sEH and the accumulation of 19,20-dihydroxydocosapentaenoic acid were increased in diabetic mouse retinas and in the retinas and vitreous humour of patients with diabetes. Mechanistically, the diol targeted the cell membrane to alter the localization of cholesterol-binding proteins, and prevented the association of presenilin 1 with N-cadherin and VE-cadherin, thereby compromising pericyte-endothelial cell interactions and inter-endothelial cell junctions. Treating diabetic mice with a specific sEH inhibitor prevented the pericyte loss and vascular permeability that are characteristic of non-proliferative diabetic retinopathy. Conversely, overexpression of sEH in the retinal Müller glial cells of non-diabetic mice resulted in similar vessel abnormalities to those seen in diabetic mice with retinopathy. Thus, increased expression of sEH is a key determinant in the pathogenesis of diabetic retinopathy, and inhibition of sEH can prevent progression of the disease.

 

[The below paper is pdf-availed.]

Analysis of <i>Fusobacterium</i> persistence and antibiotic response in colorectal cancer.

Bullman S, Pedamallu CS, Sicinska E, Clancy TE, Zhang X, Cai D, Neuberg D, Huang K, Guevara F, Nelson T, Chipashvili O, Hagan T, Walker M, Ramachandran A, Diosdado B, Serna G, Mulet N, Landolfi S, Ramon Y Cajal S, Fasani R, Aguirre AJ, Ng K, Élez E, Ogino S, Tabernero J, Fuchs CS, Hahn WC, Nuciforo P, Meyerson M.

Science. 2017 Dec 15;358(6369):1443-1448. doi: 10.1126/science.aal5240. Epub 2017 Nov 23.

PMID: 29170280

Abstract

Colorectal cancers comprise a complex mixture of malignant cells, nontransformed cells, and microorganisms. Fusobacterium nucleatum is among the most prevalent bacterial species in colorectal cancer tissues. Here we show that colonization of human colorectal cancers with Fusobacterium and its associated microbiome-including Bacteroides, Selenomonas, and Prevotella species-is maintained in distal metastases, demonstrating microbiome stability between paired primary and metastatic tumors. In situ hybridization analysis revealed that Fusobacterium is predominantly associated with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viable Fusobacterium and its associated microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced Fusobacterium load, cancer cell proliferation, and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium-associated colorectal cancer.

 

[The second below paper is pdf-availed.]

Longer life through an odd Pol enzyme.

Edgar BA, Grewal SS.

Nature. 2017 Dec 14;552(7684):182-183. doi: 10.1038/d41586-017-07435-x. No abstract available.

PMID: 29239369

https://www.nature.com/articles/d41586-017-07435-x

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RNA polymerase III limits longevity downstream of TORC1.

Filer D, Thompson MA, Takhaveev V, Dobson AJ, Kotronaki I, Green JWM, Heinemann M, Tullet JMA, Alic N.

Nature. 2017 Dec 14;552(7684):263-267. doi: 10.1038/nature25007. Epub 2017 Nov 29.

PMID: 29186112

Abstract

Three distinct RNA polymerases transcribe different classes of genes in the eukaryotic nucleus. RNA polymerase (Pol) III is the essential, evolutionarily conserved enzyme that generates short, non-coding RNAs, including tRNAs and 5S rRNA. The historical focus on transcription of protein-coding genes has left the roles of Pol III in organismal physiology relatively unexplored. Target of rapamycin kinase complex 1 (TORC1) regulates Pol III activity, and is also an important determinant of longevity. This raises the possibility that Pol III is involved in ageing. Here we show that Pol III limits lifespan downstream of TORC1. We find that a reduction in Pol III extends chronological lifespan in yeast and organismal lifespan in worms and flies. Inhibiting the activity of Pol III in the gut of adult worms or flies is sufficient to extend lifespan; in flies, longevity can be achieved by Pol III inhibition specifically in intestinal stem cells. The longevity phenotype is associated with amelioration of age-related gut pathology and functional decline, dampened protein synthesis and increased tolerance of proteostatic stress. Pol III acts on lifespan downstream of TORC1, and limiting Pol III activity in the adult gut achieves the full longevity benefit of systemic TORC1 inhibition. Hence, Pol III is a pivotal mediator of this key nutrient-signalling network for longevity; the growth-promoting anabolic activity of Pol III mediates the acceleration of ageing by TORC1. The evolutionary conservation of Pol III affirms its potential as a therapeutic target.

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Genetic Predisposition to High Blood Pressure and Lifestyle Factors: Associations with Midlife Blood Pressure Levels and Cardiovascular Events.

Pazoki R, Dehghan A, Evangelou E, Warren H, Gao H, Caulfield M, Elliott P, Tzoulaki I.

Circulation. 2017 Dec 18. pii: CIRCULATIONAHA.117.030898. doi: 10.1161/CIRCULATIONAHA.117.030898. [Epub ahead of print]

PMID: 29254930

Abstract

Background -High blood pressure (BP) is a major risk factor for cardiovascular diseases (CVD), the leading cause of mortality worldwide. Both heritable and lifestyle risk factors contribute to elevated BP levels. We aimed to investigate the extent to which lifestyle factors could offset the effect of an adverse BP genetic profile, and its effect on CVD risk. Methods -We constructed a genetic risk score for high BP using 314 published BP loci in 277,005 individuals without previous CVD from the UK Biobank study, a prospective cohort of individuals aged 40 to 69 years, with median 6.11 years of follow-up. We scored participants according to their lifestyle factors including body mass index, healthy diet, sedentary lifestyle, alcohol consumption, smoking, and urinary sodium excretion levels measured at recruitment. We examined the association between tertiles of genetic risk and tertiles of lifestyle score with BP levels and incident CVD using linear regression and Cox regression models respectively. Results -Healthy lifestyle score was strongly associated with BP (P<10-320 for systolic and diastolic BP and CVD events regardless of the underlying BP genetic risk. Participants with favorable compared to unfavorable lifestyle (bottom vs. top tertile lifestyle score) had 3.6, 3.5, and 3.6 mmHg lower systolic BP in low, middle and high genetic risk groups respectively (P for interaction= 0.0006). Similarly, favorable compared with unfavorable lifestyle showed 30%, 31%, and 33% lower risk of CVD among participants at low, middle and high genetic risk groups respectively (P for interaction= 0.99). Conclusions -Our data further support population-wide efforts to lower BP in the population via lifestyle modification. Advantages and disadvantages of disclosing genetic predisposition to high BP for risk stratification needs careful evaluation.

KEYWORDS:

AHA lifestyle recommendations; Alcohol; DASH; Genetic Risk Score; Urinary sodium and potassium excretion; cardiovascular outcomes; genetic epidemiology; genomics; myocardial infarction; stroke

 

Physical Activity Interventions in Preventing Cognitive Decline and Alzheimer-Type Dementia: A Systematic Review.

Brasure M, Desai P, Davila H, Nelson VA, Calvert C, Jutkowitz E, Butler M, Fink HA, Ratner E, Hemmy LS, McCarten JR, Barclay TR, Kane RL.

Ann Intern Med. 2017 Dec 19. doi: 10.7326/M17-1528. [Epub ahead of print]

PMID: 29255839

Abstract

BACKGROUND:

The prevalence of cognitive impairment and dementia is expected to increase dramatically as the population ages, creating burdens on families and health care systems.

PURPOSE:

To assess the effectiveness of physical activity interventions in slowing cognitive decline and delaying the onset of cognitive impairment and dementia in adults without diagnosed cognitive impairments.

DATA SOURCES:

Several electronic databases from January 2009 to July 2017 and bibliographies of systematic reviews.

STUDY SELECTION:

Trials published in English that lasted 6 months or longer, enrolled adults without clinically diagnosed cognitive impairments, and compared cognitive and dementia outcomes between physical activity interventions and inactive controls.

DATA EXTRACTION:

Extraction by 1 reviewer and confirmed by a second; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence.

DATA SYNTHESIS:

Of 32 eligible trials, 16 with low to moderate risk of bias compared a physical activity intervention with an inactive control. Most trials had 6-month follow-up; a few had 1- or 2-year follow-up. Evidence was insufficient to draw conclusions about the effectiveness of aerobic training, resistance training, or tai chi for improving cognition. Low-strength evidence showed that multicomponent physical activity interventions had no effect on cognitive function. Low-strength evidence showed that a multidomain intervention comprising physical activity, diet, and cognitive training improved several cognitive outcomes. Evidence regarding effects on dementia prevention was insufficient for all physical activity interventions.

LIMITATION:

Heterogeneous interventions and cognitive test measures, small and underpowered studies, and inability to assess the clinical significance of cognitive test outcomes.

CONCLUSION:

Evidence that short-term, single-component physical activity interventions promote cognitive function and prevent cognitive decline or dementia in older adults is largely insufficient. A multidomain intervention showed a delay in cognitive decline (low-strength evidence).

 

Effects of meal timing on changes in circulating epinephrine, norepinephrine, and acylated ghrelin concentrations: a pilot study.

Bo S, Broglio F, Settanni F, Parasiliti Caprino M, Ianniello A, Mengozzi G, De Francesco A, Fadda M, Fedele D, Guggino A, Ghigo E, Maccario M.

Nutr Diabetes. 2017 Dec 18;7(12):303. doi: 10.1038/s41387-017-0010-0.

PMID: 29255175

Abstract

BACKGROUND:

Timing of food intake impacts on metabolic diseases. Few data are available about post-meal changes in epinephrine (E), norepinephrine (NE), and acylated ghrelin (AG) at different times of the day.

SUBJECTS AND METHODS:

This randomized cross-over trial investigated E/NE/AG concentrations after identical meals consumed at 0800 or 2000 hours in 20 healthy volunteers, by standardizing diet, exercise, duration of fast, and resting. Participants randomly received the test meal at 0800 or 2000 hours, and vice versa after 1 week. Blood samples were collected before and up to 180-min post-meal, every 30 min, with participants supine, motionless, but awake.

RESULTS:

Median E levels increased at 30-60 min, then declined and rose again at 150 min; values at 60 min (19.0 vs. 15.0 ng/l, p = 0.03) and 180 min (25.0 vs. 11.0 ng/l, p < 0.001) were higher after the morning meals. NE rose at 30-60 min and then progressively declined; median values at 60 min (235.3 vs. 206.3 ng/l, p = 0.02) and 120 min (208.8 vs. 142.0 ng/l, p = 0.04) increased more after morning meals. AG progressively declined to increase again at 90 min after meal; median AG area-under-the-curve (AUC) values were lower at morning (7206.8 vs. 8828.3 pg/mL×h). AG-AUC was inversely associated with diet-induced thermogenesis (β = -121.6; 95% CI -201.0 to 42.2; p = 0.009 for each unit increase), while log NE-AUC was inversely associated with log-triglyceride AUC (β = -0.57; 95% CI -0.98 to 0.16; p = 0.015) in a multiple regression model, after multiple adjustments.

CONCLUSIONS:

In conclusion, E/NE concentrations were higher after the morning meal, while AG showed an opposite behavior. These data, although requiring confirmation in larger samples, suggest an adjunctive possible mechanism explaining the unfavorable effects of evening eating on metabolic risk.

 

Age at death as a useful indicator of healthy aging at population level: a 50-year follow-up of the Italian Rural Areas of the Seven Countries Study.

Menotti A, Puddu PE, Maiani G, Catasta G.

Aging Clin Exp Res. 2017 Dec 18. doi: 10.1007/s40520-017-0874-9. [Epub ahead of print]

PMID: 29256065

Abstract

OBJECTIVES:

To explore age at death (AD), overall and for different causes of death, in a cohort followed up to quasi-extinction.

MATERIALS AND METHODS:

In 1960, in the Italian Rural Areas of the Seven Countries Study, 1712 men aged 40-59 years were enrolled, examined and then followed up for 50 years. AD was computed for all fatal events and compared across 12 groups of causes of death. Multiple linear regression model was used to estimate AD and Cox model to predict each of the 12 causes of death, as a function of 28 selected baseline risk factors.

RESULTS:

After 50 years, 97.5% of men had died. Mean AD was 75.0 years (median 76), while large variation was found across the 12 causes of death, with the highest levels for Heart Disease of Uncertain Etiology (HDUE) and Senility plus Causes Unknown (SNUNK), having means of 79.2 and 84.5 (median of 80 and 86) years, respectively. Many risk factors were directly associated with overall AD, the most significant being subscapular skinfold, arm circumference, Mediterranean diet, age at baseline examination, never smokers and vigorous physical activity. Systolic blood pressure (SBP) was inversely related. The relevant modifiable risk factors predicting single causes of death were SBP and the lifestyle behaviors of dietary, motion and smoking habits.

CONCLUSIONS:

AD proved to be a useful indicator of previous health and aging of populations. HDUE and SNUNK seem the most "physiological" causes of death. SBP and lifestyle risk factors are the most relevant characteristics associated with AD.

KEYWORDS:

Age at death; Causes of death; Longevity; Prediction; Risk factors

 

Cereal Intake Increases and Dairy Products Decrease Risk of Cognitive Decline among Elderly Female Japanese.

Otsuka R, Kato Y, Nishita Y, Tange C, Nakamoto M, Tomida M, Imai T, Ando F, Shimokata H.

J Prev Alzheimers Dis. 2014;1(3):160-167. doi: 10.14283/jpad.2014.29.

PMID: 29251743

Abstract

BACKGROUND:

If cognitive decline can be prevented through changes in daily diet with no medical intervention, it will be highly significant for dementia prevention.

OBJECTIVES:

This longitudinal study examined the associations of different food intakes on cognitive decline among Japanese subjects.

DESIGN:

Prospective cohort study.

SETTING:

The National Institute for Longevity Sciences - Longitudinal Study of Aging, a community-based study.

PARTICIPANTS:

Participants included 298 males and 272 females aged 60 to 81 years at baseline who participated in the follow-up study (third to seventh wave) at least one time.

MEASUREMENTS:

Cognitive function was assessed with the Mini-Mental State Examination (MMSE) in all study waves. Nutritional intake was assessed using a 3-day dietary record in the second wave. Cumulative data among participants with an MMSE >27 in the second wave were analyzed using a generalized estimating equation. Multivariate adjusted odds ratios (OR) and 95% confidence intervals (CI) for an MMSE score ≤27 in each study wave according to a 1 standard deviation (SD) increase of each food intake at baseline were estimated, after adjusting for age, follow-up time, MMSE score at baseline, education, body mass index, annual household income, current smoking status, energy intake, and history of diseases.

RESULTS:

In men, after adjusting for age, and follow-up period, MMSE score at baseline, the adjusted OR for a decline in MMSE score was 1.20 (95% CI, 1.02-1.42; p=0.032) with a 1-SD increase in cereal intake. After adjusting for education and other confounding variables, the OR for a decrease in MMSE score did not reach statistical significance for this variable. In women, multivariate adjusted OR for MMSE decline was 1.43 (95% CI, 1.15-1.77; p=0.001) with a 1-SD increase in cereal intake and 0.80 (95% CI, 0.65-0.98; p=0.034) with a 1-SD increase in milk and dairy product intake.

CONCLUSIONS:

This study indicates that a 1-SD (108 g/day) decrease in cereal intake and a 1-SD (128 g/day) increase in milk and dairy product intake may have an influence of cognitive decline in community-dwelling Japanese women aged 60 years and older. Further studies are needed in order to explore the potential causal relationship.

KEYWORDS:

Cereal; Japanese; diet; elderly; milk and dairy products

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Comparison of the effect of omega-3 supplements and fresh fish on lipid profile: a randomized, open-labeled trial.

Zibaeenezhad MJ, Ghavipisheh M, Attar A, Aslani A.

Nutr Diabetes. 2017

PMID: 29259181

https://www.nature.com/articles/s41387-017-0007-8

https://www.nature.com/articles/s41387-017-0007-8.pdf

Abstract

BACKGROUND:

Dietary fish is a rich source of Omega-3 poly-unsaturated fatty acids (PUFAs). These compounds may have protective effect against cardiovascular events possibly by modifying lipid profiles. Consequently, fish oil supplements are produced commercially to complement low fish intake. It is not clear if both interventions have similar effects. The aim of this trial was to compare the anti-hyperlipidemic effect of omega3 fatty acid supplements with fresh fish.

METHOD:

A total of 106 patients with hyperlipidemia were randomized. One group received 2 g/day of omega-3 capsules for a period of 8 weeks and the other group received a mean of 250 g trout fish twice weekly (for dinner and lunch) for the same time period. The effects of these diets on the lipid profile after the intervention were compared between the two groups.

RESULTS:

Data from 48 patients in fish oil group and 47 patients from fish group was used for final analysis. In both groups, total cholesterol, non-HDL cholesterol, triglyceride (TG) levels, and Castelli I index (total cholesterol/HDL ratio) were reduced significantly following the treatment; however, dietary-fish intake had a more pronounced effect (-85.08 ± 74.82 vs. -30.75 ± 89.00, P < 0.001; 75.06 ± 35.43 vs. -16.93 ± 40.21, P < 0.001; -66.55 ± 30.79 vs. -12.7 ± 35.48, P = 0.003; and -0.77 ± 1.39 vs. -3.02 ± 1.85, P < 0.001; respectively). HDL level was increased in both groups with a higher effect in dietary fish group (4.47 ± 7.83 vs. 8.51 ± 8.79, P = 0.022). Atherogenic (Log [TG/HDL ratio]) and Castelli II (LDL/HDL ratio) indices did not change in fish oil group while were reduced significantly by fresh fish consumption (-0.04 ± 0.27 vs. -0.26 ± 0.17, P < 0.001; and 0.15 ± 0.7 vs. -1.32 ± 1.15, P < 0.001, respectively). LDL level was increased in the supplementation group, while it was significantly reduced in the dietary-fish group (+18.7 ± 24.97 vs. -22.75 ± 27.28, P < 0.001).

CONCLUSION:

Consumption of fresh fish seems to be superior in positively modifying the lipid profiles which may have important translations in the occurrence of cardiovascular events.

 

One-hour glucose value as a long-term predictor of cardiovascular morbidity and mortality: The Malmö Preventive Project.

Nielsen ML, Pareek M, Leósdóttir M, Eriksson KF, Nilsson P, Olsen MH.

Eur J Endocrinol. 2017 Dec 19. pii: EJE-17-0824. doi: 10.1530/EJE-17-0824. [Epub ahead of print]

PMID: 29259038

Abstract

OBJECTIVE:

To examine the predictive capability of a 1-hour versus 2-hour postload glucose value for cardiovascular morbidity and mortality.

DESIGN:

Prospective, population-based cohort study (Malmö Preventive Project) with subject inclusion 1974-1992.

METHODS:

4934 men without known diabetes and cardiovascular disease, who had blood glucose (BG) measured at 0, 20, 40, 60, 90 and 120 min during an OGTT (30g glucose per m2 body surface area), were followed for 27 years. Data on cardiovascular events and death were obtained through national and local registries. Predictive capabilities of fasting BG (FBG) and glucose values obtained during OGTT alone and added to a clinical prediction model comprising traditional cardiovascular risk factors were assessed using Harrell's concordance index (C-index) and integrated discrimination improvement (IDI).

RESULTS:

Median age was 48 (25th-75th percentile: 48-49) years and mean FBG 4.6 +/- 0.6 mmol/L. FBG and 2-hour postload BG did not independently predict cardiovascular events or death. Conversely, 1-hour postload BG predicted cardiovascular morbidity and mortality and remained an independent predictor of cardiovascular death (HR 1.09, 95% CI:1.01-1.17, p=0.02) and all-cause mortality (HR 1.10, 95% CI:1.05-1.16, p<0.0001) after adjusting for various traditional risk factors. Clinical risk factors with added 1-hour postload BG performed better than clinical risk factors alone, in predicting cardiovascular death (likelihood-ratio test, p=0.02) and all-cause mortality (likelihood-ratio test, p=0.0001; significant IDI, p=0.0003).

CONCLUSION:

Among men without known diabetes, addition of 1-hour BG, but not FBG or 2-hour BG, to clinical risk factors provided incremental prognostic yield for prediction of cardiovascular death and all-cause mortality.

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