Al's papers' citations and possibly links and excerpts or my synopses

[AlPater]

Carbohydrate-restricted diet promotes skin senescence in senescence-accelerated prone mice.
Wu Q, E S, Yamamoto K, Tsuduki T.
Biogerontology. 2018 Oct 3. doi: 10.1007/s10522-018-9777-1. [Epub ahead of print]
PMID: 30284122
Abstract
This study used senescence-accelerated prone mice (SAMP8) to examine the effects of a carbohydrate-restricted diet on aging and skin senescence, to determine how long-term carbohydrate restriction affects the aging process. Three-week-old male SAMP8 mice were divided into three groups after 1 week of preliminary feeding: one was given a controlled diet, the other was given a high-fat diet, and the third was given a carbohydrate-restricted diet. Ad libitum feeding was administered until the mice reached 50 weeks of age. Before the end of the test period, a grading test was used to evaluate visible aging in the mice. After the test period, serum and skin samples in mice were obtained and submitted for analysis. As a result, the grading test demonstrated that there was significant progression of visible aging in the carbohydrate-restricted group, as well as a decreased survival rate. Histological examination of the skin revealed that the epidermis and dermis in the carbohydrate-restricted group had become thinner. Analysis of the mechanisms involved demonstrated an increase in serum interleukin-6, aggravated skin senescence, inhibition of skin autophagy and activation of skin mTOR. Therefore, this study proved that a carbohydrate-restricted diet promoted skin senescence in senescence-accelerated mice.
KEYWORDS:
Aging; Autophagy; Carbohydrate-restricted diet; IL-6; Senescence-accelerated mice; mTOR

[AlPater]

Why some doctors are saying it's time to 'drop the D'
Major study published this week dampens the hype around the 'sunshine' vitamin and bone health
Marcy Cuttler · CBC News · Posted: Oct 06, 2018
https://www.cbc.ca/news/health/vitamin-d-bone-health-study-ineffective-lancet-1.4852428
>>>>>>>>>>>>>>
Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis
Mark J Bolland, PhD 
Andrew Grey, Alison Avenell
Summary
Background
The effects of vitamin D on fractures, falls, and bone mineral density are uncertain, particularly for high vitamin D doses. We aimed to determine the effect of vitamin D supplementation on fractures, falls, and bone density.
Methods
In this systematic review, random-effects meta-analysis, and trial sequential analysis, we used findings from literature searches in previously published meta-analyses. We updated these findings by searching PubMed, Embase, and Cochrane Central on Sept 14, 2017, and Feb 26, 2018, using the search term “vitamin D” and additional keywords, without any language restrictions. We assessed randomised controlled trials of adults (>18 years) that compared vitamin D with untreated controls, placebo, or lower-dose vitamin D supplements. Trials with multiple interventions (eg, co-administered calcium and vitamin D) were eligible if the study groups differed only by use of vitamin D. We excluded trials of hydroxylated vitamin D analogues. Eligible studies included outcome data for total or hip fractures, falls, or bone mineral density measured at the lumbar spine, total hip, femoral neck, total body, or forearm. We extracted data about participant characteristics, study design, interventions, outcomes, funding sources, and conflicts of interest. The co-primary endpoints were participants with at least one fracture, at least one hip fracture, or at least one fall; we compared data for fractures and falls using relative risks with an intention-to-treat analysis using all available data. The secondary endpoints were the percentage change in bone mineral density from baseline at lumbar spine, total hip, femoral neck, total body, and forearm.
Findings
We identified 81 randomised controlled trials (n=53 537 participants) that reported fracture (n=42), falls (n=37), or bone mineral density (n=41). In pooled analyses, vitamin D had no effect on total fracture (36 trials; n=44 790, relative risk 1·00, 95% CI 0·93–1·07), hip fracture (20 trials; n=36 655, 1·11, 0·97–1·26), or falls (37 trials; n=34 144, 0·97, 0·93–1·02). Results were similar in randomised controlled trials of high-dose versus low-dose vitamin D and in subgroup analyses of randomised controlled trials using doses greater than 800 IU per day. In pooled analyses, there were no clinically relevant between-group differences in bone mineral density at any site (range −0·16% to 0·76% over 1–5 years). For total fracture and falls, the effect estimate lay within the futility boundary for relative risks of 15%, 10%, 7·5%, and 5% (total fracture only), suggesting that vitamin D supplementation does not reduce fractures or falls by these amounts. For hip fracture, at a 15% relative risk, the effect estimate lay between the futility boundary and the inferior boundary, meaning there is reliable evidence that vitamin D supplementation does not reduce hip fractures by this amount, but uncertainty remains as to whether it might increase hip fractures. The effect estimate lay within the futility boundary at thresholds of 0·5% for total hip, forearm, and total body bone mineral density, and 1·0% for lumbar spine and femoral neck, providing reliable evidence that vitamin D does not alter these outcomes by these amounts.
Interpretation
Our findings suggest that vitamin D supplementation does not prevent fractures or falls, or have clinically meaningful effects on bone mineral density. There were no differences between the effects of higher and lower doses of vitamin D. There is little justification to use vitamin D supplements to maintain or improve musculoskeletal health. This conclusion should be reflected in clinical guidelines.

 

Dietary intake of magnesium and the risk of epilepsy in middle-aged and older Finnish men: A 22-year follow-up study in a general population.
Yary T, Kauhanen J.
Nutrition. 2018 Jul 12;58:36-39. doi: 10.1016/j.nut.2018.06.019. [Epub ahead of print]
PMID: 30273823
Abstract
OBJECTIVES:
Magnesium may play an important role in the prevention or treatment of epilepsy. We aimed to examine the association between dietary intake of magnesium and the incidence of epilepsy in middle-aged Finnish men in a prospective setting. As a secondary analysis, we also considered a possible association between dietary intake of magnesium and inflammation in subjects with epilepsy.
METHODS:
The study included 2442 men, ages 42 to 60 y, from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study who were free of epilepsy at baseline between 1984 and 1989. Dietary intake of magnesium was assessed with a 4-d food record. The hospital discharge diagnosis of epilepsy was used as an outcome variable.
RESULTS:
During the average follow-up period of 22.4 y, 74 men (3%) developed epilepsy. Those who followed the recommended dietary intake (>350 mg/d) of magnesium had a lower risk of epilepsy (hazard ratio {HR}: 0.52; confidence interval [CI], 0.28-0.99; P = 0.045) after multivariate adjustments. However, the risk was not significant after adjustment for C-reactive protein (CRP). We also found that CRP concentration was directly associated with the risk of epilepsy (HR: 1.24; CI, 1.00-1.54; P = 0.048). This association was attenuated after adjustment for dietary intake of magnesium and no longer significantly associated with the risk of epilepsy (HR: 1.22; CI, 0.99-1.52; P = 0.07).
CONCLUSIONS:
A higher dietary intake of magnesium was associated with lower incident epilepsy, and this association was slightly mediated by CRP. Further studies are required to identify the potential mechanisms.
KEYWORDS:
C-reactive protein; Epilepsy; Magnesium; Seizure

Erythrocyte Saturated Fatty Acids and Incident Type 2 Diabetes in Chinese Men and Women: A Prospective Cohort Study.
Lin JS, Dong HL, Chen GD, Chen ZY, Dong XW, Zheng JS, Chen YM.
Nutrients. 2018 Oct 1;10(10). pii: E1393. doi: 10.3390/nu10101393.
PMID: 30275386 Free Article
Abstract
The association between circulating saturated fatty acids (SFAs) and incident type 2 diabetes (T2D) is reported in Western populations with inconsistent results, while evidence from Asian populations is scarce. We aimed to examine the associations between erythrocyte SFAs and incident T2D in a Chinese population. Between 2008 and 2013, a total of 2683 participants, aged 40⁻75 years, free of diabetes were included in the present analyses. Incident T2D cases were ascertained during follow-up visits. Gas chromatography was used to measure erythrocyte fatty acids at baseline. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). During 13,508 person years of follow-up, 216 T2D cases were identified. Compared with the first quartile, multivariable-adjusted HRs (95% CIs) of the fourth quartile were 1.20 (0.82⁻1.76; p = 0.242) for myristic acid (14-carbon tail, zero double bonds; 14:0), 0.69 (0.48⁻0.99; p = 0.080) for palmitic acid (16:0), 1.49 (1.02⁻2.19; p = 0.047) for stearic acid (18:0), 1.46 (1.00⁻2.12; p = 0.035) for arachidic acid (20:0), 1.48 (0.99⁻2.22; p = 0.061) for behenic acid (22:0), and 1.08 (0.74⁻1.56; p = 0.913) for lignoceric acid (24:0). Our findings indicate that individual erythrocyte SFAs are associated with T2D in different directions, with 18:0 and 20:0 SFAs positively associated with the risk, whereas no convincing inverse association for 16:0 SFAs.
KEYWORDS:
erythrocyte; prospective cohort; saturated fatty acids; type 2 diabetes

Effect of resveratrol supplementation on lipid profile in subjects with dyslipidemia: A randomized double-blind, placebo-controlled trial.
Simental-Mendía LE, Guerrero-Romero F.
Nutrition. 2018 Jul 12;58:7-10. doi: 10.1016/j.nut.2018.06.015. [Epub ahead of print]
PMID: 30278430
Abstract
OBJECTIVES:
The aim of this study was to explore the effect of resveratrol supplementation on lipid profile in individuals with dyslipidemia.
METHODS:
Apparently healthy men and non-pregnant women 20 to 65 y of age with new diagnosis of dyslipidemia were enrolled in a randomized double-blind, placebo-controlled trial and randomly allocated to receive either resveratrol 100mg/d or placebo (sucrose 0.5 g/d) for 2 mo. Smoking, alcohol intake, diabetes, acute or chronic renal or hepatic diseases, malignancy, cardiovascular disease, serum triacylglycerol levels ≥400mg/dL, low-density lipoprotein cholesterol levels ≥190mg/dL, and consumption of lipid-lowering drugs or supplements containing resveratrol were exclusion criteria.
RESULTS:
Seventy-one individuals with new diagnosis of dyslipidemia were enrolled and randomly allocated to the resveratrol (n = 35) or placebo groups (n = 36). At baseline, there were no significant differences between the study groups. After intervention period, individuals in the resveratrol group showed a significant decrease in total cholesterol (201.4 ± 34.4 versus 220.6 ± 37.4, P = 0.04) and triacylglycerol (133.4 ± 55.3 versus 166.7 ± 68.5, P = 0.04) concentrations compared with the placebo group, without significant statistical differences for high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels.
CONCLUSION:
The results suggest that resveratrol supplementation significantly reduces total cholesterol and triacylglycerol concentrations in individuals with dyslipidemia.
KEYWORDS:
Dyslipidemia; Lipid profile; Lipids; Randomized controlled trial; Resveratrol

Sugar-sweetened beverage consumption and incidence of breast cancer: the Seguimiento Universidad de Navarra (SUN) Project.
Romanos-Nanclares A, Toledo E, Gardeazabal I, Jiménez-Moleón JJ, Martínez-González MA, Gea A.
Eur J Nutr. 2018 Oct 3. doi: 10.1007/s00394-018-1839-2. [Epub ahead of print]
PMID: 30284064
Abstract
PURPOSE:
Breast cancer (BC) incidence is increasing worldwide. Higher insulin resistance may potentially lead to an increased risk of BC. Sugar-sweetened beverages (SSB) are an acknowledged dietary factor that increases insulin resistance. However, the association between SSB and BC has not been widely explored. We evaluated the association between baseline consumption of SSB and the incidence of BC among relatively young women in a cohort of Spanish university graduates.
METHODS:
We evaluated 10,713 middle-aged, Spanish female university graduates (median age 33) from the Seguimiento Universidad de Navarra (SUN) cohort, initially free of BC. SSB consumption was collected at baseline using a validated 136-item semi-quantitative food-frequency questionnaire. Incidence of BC was confirmed by a trained oncologist using medical records. We fitted Cox regression models to assess the relationship between baseline categories of SSB consumption and the incidence of BC during follow-up. We stratified the analyses by menopausal status.
RESULTS:
During 106,189 person-years follow-up, 100 incident cases of BC were confirmed. Among postmenopausal women, regular consumption of SSB was associated with a significantly higher incidence of BC (HR 2.12; 95% CI 1.02, 4.41) in the fully adjusted model, compared to women who never or seldom consumed SSB. No association was found among premenopausal women (HR 1.16; 95% CI 0.66, 2.07).
CONCLUSIONS:
Even though the number of cases was small, in this Mediterranean cohort, we observed a direct association between SSB consumption and BC risk among postmenopausal women. Nonetheless further larger longitudinal studies are needed to support this association.
KEYWORDS:
Breast cancer; Cohort; Primary prevention; Sugar-sweetened beverage

Effect of Increased Daily Water Intake in Premenopausal Women With Recurrent Urinary Tract Infections: A Randomized Clinical Trial.
Hooton TM, Vecchio M, Iroz A, Tack I, Dornic Q, Seksek I, Lotan Y.
JAMA Intern Med. 2018 Oct 1. doi: 10.1001/jamainternmed.2018.4204. [Epub ahead of print]
PMID: 30285042
Abstract
IMPORTANCE:
Increased hydration is often recommended as a preventive measure for women with recurrent cystitis, but supportive data are sparse.
OBJECTIVE:
To assess the efficacy of increased daily water intake on the frequency of recurrent cystitis in premenopausal women.
DESIGN, SETTING, AND PARTICIPANTS:
Randomized, open-label, controlled, 12-month trial at a clinical research center (years 2013-2016). Among 163 healthy women with recurrent cystitis (≥3 episodes in past year) drinking less than 1.5 L of fluid daily assessed for eligibility, 23 were excluded and 140 assigned to water or control group. Assessments of daily fluid intake, urinary hydration, and cystitis symptoms were performed at baseline, 6- and 12-month visits, and monthly telephone calls.
INTERVENTIONS:
Participants were randomly assigned to drink, in addition to their usual fluid intake, 1.5 L of water daily (water group) or no additional fluids (control group) for 12 months.
MAIN OUTCOMES AND MEASURES:
Primary outcome measure was frequency of recurrent cystitis over 12 months. Secondary outcomes were number of antimicrobial regimens used, mean time interval between cystitis episodes, and 24-hour urinary hydration measurements.
RESULTS:
The mean (SD) age of the 140 participants was 35.7 (8.4) years, and the mean (SD) number of cystitis episodes in the previous year was 3.3 (0.6). During the 12-month study period, the mean (SD) number of cystitis episodes was 1.7 (95% CI, 1.5-1.8) in the water group compared with 3.2 (95% CI, 3.0-3.4) in the control group, with a difference in means of 1.5 (95% CI, 1.2-1.8; P < .001). Overall, there were 327 cystitis episodes, 111 in the water group and 216 in the control group. The mean number of antimicrobial regimens used to treat cystitis episodes was 1.9 (95% CI, 1.7-2.2) and 3.6 (95% CI, 3.3-4.0), respectively, with a difference in means of 1.7 (95% CI, 1.3-2.1; P < .001). The mean time interval between cystitis episodes was 142.8 (95% CI, 127.4-160.1) and 84.4 (95% CI, 75.4-94.5) days, respectively, with a difference in means of 58.4 (95% CI, 39.4-77.4; P < .001). Between baseline and 12 months, participants in the water group, compared with those in the control group, had increased mean (SD) urine volume (1.4 [0.04] vs 0.1 [0.04] L; P < .001) and voids (2.4 [0.2] vs -0.1 [0.2]; P < .001) and decreased urine osmolality (-402.8 [19.6] vs -24.0 [19.5] mOsm/kg; P < .001).
CONCLUSIONS AND RELEVANCE:
Increased water intake is an effective antimicrobial-sparing strategy to prevent recurrent cystitis in premenopausal women at high risk for recurrence who drink low volumes of fluid daily.

Edited October 6, 2018 by AlPater

[AlPater]

Nutritional epidemiology and cancer: A Tale of Two Cities.
Giovannucci E.
Cancer Causes Control. 2018 Oct 5. doi: 10.1007/s10552-018-1088-y. [Epub ahead of print]
PMID: 30291578
https://sci-hub.tw/10.1007/s10552-018-1088-y
Abstract
Recently, Ioannidis questioned whether nutritional epidemiology could be reconciled with good scientific principles, and suggested that the field needs radical reform. One of the reforms he advocated was more randomized trials; though what diet would be tested and how it would be measured were unspecified, how adherence would be monitored was unclear or unimportant, and the length of time vaguely stated as "lifelong". The other reform was reanalysis of shared data, which actually already exists in a large number of cohort consortia of individual pooled data. The 2018 report analysis of diet and cancer from the World Cancer Fund/American Institute of Cancer Research presents a sharply different picture of our knowledge of nutrition and cancer, which has evolved immensely in the past 3 decades. Based on current knowledge, factors related to energy balance, encompassed by body mass anthropometric measures might account for about 10-15% of the U.S. cancer burden. This 10-15% encompasses physical activity and obesogenic effects of diet. About 5% may be attributable to alcohol, and another 5% to specific dietary factors combined (e.g., red and processed meat, whole grains, fiber, calcium, fruits, and vegetables). Surrogates such as attained height and age at menarche are influenced by nutrition and are consistent risk factors for cancer, supporting the importance of early nutrition. Recent data suggest that early life dietary patterns, which may be modifiable, may be important. Though important questions remain, our understanding of nutrition and cancer over the life course is coherent and has been informed by nutritional epidemiology and other data.
KEYWORDS:
Cancer; Diet; Epidemiology; Nutritional epidemiology

[AlPater]

Influence of corticosterone on growth, home-cage activity, wheel running, and aerobic capacity in house mice selectively bred for high voluntary wheel-running behavior.
Singleton JM, Garland T Jr.
Physiol Behav. 2018 Oct 4. pii: S0031-9384(18)30459-1. doi: 10.1016/j.physbeh.2018.10.001. [Epub ahead of print]
PMID: 30292826
https://sci-hub.tw/https://linkinghub.elsevier.com/retrieve/pii/S0031938418304591
Abstract
Glucocorticoids, a class of metabolic hormones, impact a wide range of traits (e.g., behavior, skeletal growth, muscle maintenance, glucose metabolism), and variation in concentrations of circulating glucocorticoids (such as corticosterone), at the level of natural individual variation, in relation to endocrine disorders, or from exogenous supplementation, have manifold effects. Changes in circulating corticosterone concentrations can also impact multiple aspects of locomotor behavior, including both motivation and physical ability for exercise. To examine further the role of corticosterone in locomotor behavior and associated traits, we utilized laboratory house mice from a long-term experiment that selectively breeds for high levels of voluntary exercise. As compared with four non-selected control (C) lines, mice from the four replicate High Runner (HR) lines have ~2-fold higher baseline circulating corticosterone concentrations as well as ~3-fold higher voluntary wheel running on a daily basis, higher home-cage activity when deprived of wheels, higher maximal aerobic capacity, and smaller body size; potentially, all of these differences could be modulated by circulating corticosterone. We administered 50 μg/ml corticosterone-21-hemisuccinate in the drinking water of both HR and C male mice from weaning through ~8 weeks of age. As compared with mice from C lines, HR mice had higher endogenous corticosterone levels; higher daily wheel-running distance, duration, and speed; higher maximal oxygen consumption during forced exercise (VO2max); spent more time in the closed arms of an elevated plus maze; and had larger reproductive fat pads. For both HR and C mice, corticosterone treatment strongly suppressed endogenous circulating corticosterone levels, decreased growth rate and adult body mass, increased food and water consumption (both adjusted for body mass), increased entries into closed arms of an elevated plus maze, decreased home-cage activity (total and average intensity), decreased wheel-running distance and maximum speed, and decreased VO2max. At the suborganismal level, corticosterone treatment decreased relative adrenal, liver, and triceps surae muscle mass, as well as tail length, but increased both subdermal and reproductive fat pad masses, as well as hematocrit. Overall, the responses of both HR and C mice to corticosterone supplementation were "negative" from a health perspective. These results have significant implications for understanding both the evolution of baseline corticosterone levels and stress-related effects on activity levels. They also suggest that patients experiencing extended periods of glucocorticoid treatment might benefit from attempts to increase their physical activity as an adjuvant.
KEYWORDS:
Artificial selection; Body composition; Exercise; Food consumption; Growth; Locomotion

Population-based studies of relationships between dietary acidity load, insulin resistance and incident diabetes in Danes.
Gæde J, Nielsen T, Madsen ML, Toft U, Jørgensen T, Overvad K, Tjønneland A, Hansen T, Allin KH, Pedersen O.
Nutr J. 2018 Oct 6;17(1):91. doi: 10.1186/s12937-018-0395-1.
PMID: 30292239
https://nutritionj.biomedcentral.com/track/pdf/10.1186/s12937-018-0395-1
Abstract
BACKGROUND:
It has been suggested that the acidity of the diet may be related to increased risk of type 2 diabetes. To investigate this hypothesis, we tested if the acidity of the diet, measured as the Potential Renal Acid Load (PRAL) score, was associated with incident diabetes and diabetes-related intermediary traits.
METHODS:
A total of 54,651 individuals from the Danish Diet, Cancer and Health (DCH) cohort were included in the prospective cox regression analyses of incident diabetes over a 15 years follow-up period. Moreover, 5724 Danish individuals with baseline data from the Inter99 cohort were included in the cross sectional, multivariate and logistic regression analyses of measures of insulin sensitivity, insulin release and glucose tolerance status derived from an oral glucose tolerance test (OGTT).
RESULTS:
In the DCH cohort a trend analysis showed that quintiles of PRAL score were, after multifactorial adjustment, associated with a higher incidence of diabetes (ptrend = 6 × 10- 7). HR for incident diabetes was 1.24 (1.14; 1.35) (p = 7 × 10- 7) between first and fifth PRAL score quintile. In Inter99 higher PRAL score associated with insulin resistance as estimated by lower BIGTT-Si (an OGTT-derived index of insulin sensitivity) (p = 4 × 10- 7) and Matsuda index of insulin sensitivity (p = 2 × 10- 5) as well as higher HOMA-IR (p = 0.001). No association was observed for measures of insulin release, but higher PRAL score was associated with lower OGTT-based disposition index.
CONCLUSIONS:
A high dietary acidity load is associated with a higher risk of diabetes among middle-aged Danes. Although adjustment for BMI attenuated the effect sizes the association remained significant. The increased risk of diabetes may be related to our finding that a high dietary acidity load associates with impaired insulin sensitivity.
KEYWORDS:
Dietary acid load; Disposition index; Glucose; Insulin resistance; PRAL; Type 2 diabetes

[AlPater]

Intermittent administration of a leucine-deprived diet is able to intervene in type 2 diabetes in db/db mice.
Wei S, Zhao J, Wang S, Huang M, Wang Y, Chen Y.
Heliyon. 2018 Sep 27;4(9):e00830. doi: 10.1016/j.heliyon.2018.e00830. eCollection 2018 Sep.
PMID: 30294696
Abstract
Continuous deficiency of leucine, a member of branched chain amino acids, is able to reduce obesity and improve insulin sensitivity in mice. Intermittent fasting has been shown to be effective in intervention of metabolic disorders including diabetes. However, it is unknown whether intermittent leucine deprivation can intervene in type 2 diabetes progression. We administered leucine-deprived food every other day in db/db mice, a type 2 diabetes model, for a total of eight weeks to investigate the interventional effect of intermittent leucine deprivation. Intermittent leucine deprivation significantly reduces hyperglycemia in db/db mice independent of body weight change, together with improvement in glucose tolerance and insulin sensitivity. The total area of pancreatic islets and β cell number are increased by intermittent leucine deprivation, accompanied by elevated proliferation of β cells. The expression level of Ngn3, a β cell progenitor marker, is also increased by leucine-deleted diet. However, leucine deficiency engenders an increase in fat mass and a decrease in lean mass. Lipid accumulation in the liver is elevated and liver function is compromised by leucine deprivation. In addition, leucine deficiency alters the composition of gut microbiota. Leucine deprivation increases the genera of Bacteroides, Alloprevotella, Rikenellaceae while reduces Lachnospiraceae and these changes are correlated with fasting blood glucose levels of the mice. Collectively, our data demonstrated that intermittent leucine deprivation can intervene in the progression of type 2 diabetes in db/db mice. However, leucine deficiency reduces lean mass and aggravates hepatic steatosis in the mouse.

Human Umbilical Cord Blood Plasma Alleviates Age-related Olfactory Dysfunction by Attenuating Peripheral TNF-α expression.
Lee BC, Kang I, Lee SE, Lee JY, Shin N, Kim JJ, Choi SW, Kang KS.
BMB Rep. 2018 Oct 8. pii: 4223. [Epub ahead of print]
PMID: 30293545
pdf available from http://submit.bmbreports.org/Search/View.html?tmp_tr_num=4223
Abstract
Social requirements are needed for living in an aging society and individual longevity. Among them, improved health and medical cares, appropriate for an aging society are strongly demanded. Human cord blood-derived plasma (hUCP) has recently emerged for its unique anti-aging effects. In this study, we investigated brain rejuvenation, particularly olfactory function, that could be achieved by a systemic administration of young blood and its underlying mechanisms. Older than 24-month-old mice were used as an aged group and administered with intravenous injection of hUCP repetitively, eight times. Anti-aging effect of hUCP on olfactory function was evaluated by buried food finding test. To investigate the mode of action of hUCP, brain, serum and spleen of mice were collected for further ex vivo analyses. Systemic injection of hUCP improved aging-associated olfactory deficits, reducing time for finding food. In the brain, although an infiltration of activated microglia and its expression of cathepsin S remarkably decreased, significant changes of proinflammatory factors were not detected. Conversely, peripheral immune balance distinctly switched from predominance of Type 1 helper T (Th1) cells to alternative regulatory T cells (Tregs). These findings indicate that systemic administration of hUCP attenuates age-related neuroinflammation and subsequent olfactory dysfunction by modulating peripheral immune balance toward Treg cells, suggesting another therapeutic function and mechanism of hUCP administration.

[AlPater]

Effect of Low Dose Docosahexaenoic Acid-Rich Fish Oil on Plasma Lipids and Lipoproteins in Pre-Menopausal Women: A Dose⁻Response Randomized Placebo-Controlled Trial.
Sparkes C, Gibson R, Sinclair A, Else PL, Meyer BJ.
Nutrients. 2018 Oct 8;10(10). pii: E1460. doi: 10.3390/nu10101460.
PMID: 30297663
https://www.mdpi.com/2072-6643/10/10/1460/htm
Abstract
Omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation has been shown to improve plasma lipid profiles in men and post-menopausal women, however, data for pre-menopausal women are lacking. The benefits of intakes less than 1 g/day have not been well studied, and dose⁻response data is limited. The aim of this study was to determine the effect of low doses of docosahexaenoic acid (DHA)-rich tuna oil on plasma triglyceride (TG) lowering in pre-menopausal women, and investigate if low dose DHA-rich tuna oil supplementation would increase the low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle sizes. A randomized, double-blind, placebo-controlled trial was conducted, in which 53 healthy pre-menopausal women with mildly elevated plasma TG levels consumed 0, 0.35, 0.7, or 1 g/day n-3 LCPUFA as HiDHA™ tuna oil or placebo (Sunola oil) capsules for 8 weeks. Supplementation with 1 g/day n-3 LCPUFA, but not lower doses, reduced plasma TG by 23% in pre-menopausal women. This was reflected in a dose-dependent reduction in very-low-density lipoprotein (VLDL)-TG (R² = 0.20, p = 0.003). A weak dose-dependent shift in HDL (but not LDL) particle size was identified (R² = 0.05, p = 0.04). The results of this study indicate that DHA-rich n-3 LCPUFA supplementation at a dose of 1 g/day is an effective TG-lowering agent and increases HDL particle size in pre-menopausal women.
KEYWORDS:
DHA; lipoproteins; plasma lipids; premenopausal women

[AlPater]

Fasting enhances extinction retention and prevents the return of fear in humans.
Shi L, Deng J, Chen S, Que J, Sun Y, Wang Z, Guo X, Han Y, Zhou Y, Zhang X, Xie W, Lin X, Shi J, Lu L.
Transl Psychiatry. 2018 Oct 9;8(1):214. doi: 10.1038/s41398-018-0260-1.
PMID: 30301955
https://www.nature.com/articles/s41398-018-0260-1
Abstract
Fear is prone to return following extinction that is the basis of exposure therapy for fear-related disorders. Manipulations that enhance the extinction process can be beneficial for treatment. Animal studies have shown that fasting or caloric restriction can enhance extinction and inhibit the return of fear. The present study examined the effects of fasting on fear acquisition, extinction, and the return of fear in humans. One hundred and twenty-five male participants were randomized into a fasting group and food group and exposed to a Pavlovian fear conditioning paradigm. Changes in plasma cortisol and ghrelin levels were examined using enzyme-linked immunosorbent assays. One-night fasting had no effect on fear acquisition but enhanced fear extinction retention and prevented the return of fear, and this effect persisted for at least 6 months. This procedure was also effective for remote fear memory. Plasma ghrelin levels were elevated after fasting and had a negative relationship with the fear response in spontaneous recovery test. However, overnight fasting did not affect cortisol levels. These findings indicate that fasting enhances extinction retention and prevents the return of fear, without influencing fear memory formation. We propose that this novel procedure may open new avenues for promoting extinction-based therapies for fear-related disorders.

Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans?
Madeo F, Bauer MA, Carmona-Gutierrez D, Kroemer G.
Autophagy. 2018 Oct 11:1-4. doi: 10.1080/15548627.2018.1530929. [Epub ahead of print]
PMID: 30306826
https://sci-hub.tw/10.1080/15548627.2018.1530929
Abstract
Spermidine is a natural polyamine that stimulates cytoprotective macroautophagy/autophagy. External supplementation of spermidine extends lifespan and health span across species, including in yeast, nematodes, flies and mice. In humans, spermidine levels decline with aging, and a possible connection between reduced endogenous spermidine concentrations and age-related deterioration has been suggested. Recent epidemiological data support this notion, showing that an increased uptake of this polyamine with spermidine-rich food diminishes overall mortality associated with cardiovascular diseases and cancer. Here, we discuss nutritional and other possible routes to counteract the age-mediated decline of spermidine levels.
KEYWORDS:
Autophagy; cancer; cardiovascular diseases; health span extension; longevity

Acute Effects of Substitution, and Addition, of Carbohydrates and Fat to Protein on Gastric Emptying, Blood Glucose, Gut Hormones, Appetite, and Energy Intake.
Giezenaar C, Lange K, Hausken T, Jones KL, Horowitz M, Chapman I, Soenen S.
Nutrients. 2018 Oct 7;10(10). pii: E1451. doi: 10.3390/nu10101451.
PMID: 30301241
https://www.mdpi.com/2072-6643/10/10/1451/htm
Abstract
Whey protein, when ingested on its own, load-dependently slows gastric emptying and stimulates gut hormone concentrations in healthy young men. The aim of this study was to determine the effects of substitution, and addition, of carbohydrate (dextrose) and fat (olive oil) to whey protein. In randomized, double-blind order, 13 healthy young men (age: 23 ± 1 years, body mass index: 24 ± 1 kg/m²) ingested a control drink (450 mL; ~2 kcal/'control') or iso-volumetric drinks containing protein/carbohydrate/fat: (i) 14 g/28 g/12.4 g (280 kcal/'M280'), (ii) 70 g/28 g/12.4 g (504kcal/'M504'), and (iii) 70 g/0 g/0 g (280 kcal/'P280'), on 4 separate study days. Gastric emptying (n = 11, 3D-ultrasonography), blood glucose, plasma insulin, ghrelin, cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) concentrations (0⁻180 min), appetite (visual analogue scales), and ad-libitum buffet-meal energy intake (180⁻210 min) were determined. Substitution of protein with carbohydrate and fat was associated with faster gastric emptying (lower 50% emptying time (T50)), reduced suppression of ghrelin, and stimulation of GLP-1 (all P < 0.001); while the addition of carbohydrate and fat to protein did not affect gastric emptying or gut hormone responses significantly. Total energy intake (i.e., drink plus meal) was greater after all caloric drinks than control (P < 0.001). In conclusion, substitution of whey protein with dextrose and olive oil accelerated gastric emptying. Higher protein content of a mixed macronutrient drink increased gut hormone and insulin responses.
KEYWORDS:
appetite; blood glucose; gastric emptying; gut hormones; whey protein

Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.
Imamura F, Fretts A, Marklund M, Ardisson Korat AV, Yang WS, Lankinen M, Qureshi W, Helmer C, Chen TA, Wong K, Bassett JK, Murphy R, Tintle N, Yu CI, Brouwer IA, Chien KL, Frazier-Wood AC, Del Gobbo LC, Djoussé L, Geleijnse JM, Giles GG, de Goede J, Gudnason V, Harris WS, Hodge A, Hu F; InterAct Consortium, Koulman A, Laakso M, Lind L, Lin HJ, McKnight B, Rajaobelina K, Risérus U, Robinson JG, Samieri C, Siscovick DS, Soedamah-Muthu SS, Sotoodehnia N, Sun Q, Tsai MY, Uusitupa M, Wagenknecht LE, Wareham NJ, Wu JH, Micha R, Forouhi NG, Lemaitre RN, Mozaffarian D; Fatty Acids and Outcomes Research Consortium (FORCE).
PLoS Med. 2018 Oct 10;15(10):e1002670. doi: 10.1371/journal.pmed.1002670. eCollection 2018 Oct.
PMID: 30303968
Abstract
BACKGROUND:
We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D).
METHODS AND FINDINGS:
Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, triglycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95% CI) for incident T2D per cohort-specific 10th to 90th percentile range of 15:0 was 0.80 (0.73-0.87); of 17:0, 0.65 (0.59-0.72); of t16:1n7, 0.82 (0.70-0.96); and of their sum, 0.71 (0.63-0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men (pinteraction < 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist.
CONCLUSIONS:
In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D.

The Effects of Dietary Flaxseed on Cardiac Arrhythmias and Claudication in Patients with Peripheral Arterial Disease.
Rodriguez Leyva D, Rodriguez-Portelles A, Weighell W, Guzman R, Maddaford TG, Pierce GN.
Can J Physiol Pharmacol. 2018 Oct 11. doi: 10.1139/cjpp-2018-0280. [Epub ahead of print]
PMID: 30308127
Abstract
Patients with peripheral artery disease (PAD) are at increased risk for cardiovascular events and higher susceptibility for cardiac arrhythmias may be involved. The objectives of this double blinded, randomized controlled FLAX-PAD trial were to determine whether daily consumption of a diet supplemented with 30g of milled flaxseed (or placebo) over one year by PAD patients has effects on the prevalence of cardiac arrhythmias and exercise capacity. Cardiac arrhythmias were assessed on a cardiac stress test and at rest. At baseline, the PAD patients had a high incidence of cardiac arrhythmias (48% in the flaxseed group and 32% in the placebo group). After 1 year, the presence of cardiac arrhythmias in the flaxseed group decreased by 2% and increased by 12% in the placebo group (P>0.05). Electrocardiographic variables (P, PR, QRS, QT, QTc) did not change in either group during the trial. Patients from both groups improved initial and absolute claudication distances but the intergroup difference was also not statistically significant. In summary, the prevalence of cardiac arrhythmias and physical capacity trended in a positive direction for patients ingesting flaxseed but either a larger sample size or a longer intervention with flaxseed may be required to show statistically significant differences.

[AlPater]

Diet-quality scores and the risk of symptomatic gallstone disease: a prospective cohort study of male US health professionals.
Wirth J, Song M, Fung TT, Joshi AD, Tabung FK, Chan AT, Weikert C, Leitzmann M, Willett WC, Giovannucci E, Wu K.
Int J Epidemiol. 2018 Oct 11. doi: 10.1093/ije/dyy210. [Epub ahead of print]
PMID: 30312404
Abstract
OBJECTIVE:
To investigate the association between three diet-quality scores corresponding to adherence to healthy dietary patterns [alternate Mediterranean (aMed), Alternate Healthy Eating Index (AHEI-2010), Dietary Approaches to Stop Hypertension (DASH)] and the risk of symptomatic gallstone disease.
METHODS:
The study comprised 43 635 men of the Health Professionals Follow-up Study-an ongoing prospective cohort study of US health professionals. Participants were free of symptomatic gallstone disease and diabetes and provided dietary information every 4 years from 1986 (baseline) until 2012. The aMed, AHEI-2010 and DASH scores were generated and associated with the risk of symptomatic gallstone disease using Cox proportional hazards regression.
RESULTS:
During 716 904 person-years of follow-up, 2382 incident cases of symptomatic gallstone disease were identified. All three scores were inversely associated with risk of symptomatic gallstone disease after adjustment for potential confounders including age, smoking, physical activity, energy and coffee intake [hazard ratios (HRs) and 95% confidence intervals (CIs)] comparing the highest with the lowest quintiles: aMed: 0.66 (0.57-0.77), AHEI-2010: 0.64 (0.56-0.74) and DASH: 0.66 (0.58-0.76)]. Findings were similar after additional adjustment for body mass index and after inclusion of asymptomatic cases. Associations were stronger when analysis was restricted to cases who had undergone cholecystectomy.
CONCLUSIONS:
In this prospective cohort of male US health professionals, higher adherence to the aMed, AHEI-2010 and DASH diets was associated with lower risk of symptomatic gallstone disease. Dietary recommendations focusing on high-quality diets targeting symptomatic gallstone disease may lower the incidence of this prevalent disease.

Exposure to pollen-bound pesticide mixtures induces longer-lived but less efficient honey bees.
Prado A, Pioz M, Vidau C, Requier F, Jury M, Crauser D, Brunet JL, Le Conte Y, Alaux C.
Sci Total Environ. 2019 Feb 10;650(Pt 1):1250-1260. doi: 10.1016/j.scitotenv.2018.09.102. Epub 2018 Sep 8.
PMID: 30308813
Abstract
Due to the widespread use of pesticides and their persistence in the environment, non-target organisms are chronically exposed to mixtures of toxic residues. Fungicides, herbicides and insecticides are all found at low doses in the diet of pollinators such as honey bees, but due to the lack of data on the toxicological effects of these mixtures, determining their risk is difficult to assess. We therefore developed a study combining the identification of common pollen-bound pesticide mixtures associated with poor colony development and tested their effects on bee behavior and physiology. We exposed bees to the identified pesticide mixtures during the first days of their adult life, a crucial period for physiological development. Using optic bee counters we recorded the behavior of bees throughout their lives and identified two pesticide mixtures that delay the onset of foraging and slow-down foraging activity. Furthermore, one of these mixtures hampers pollen foraging. As bee longevity is strongly influenced by the time spent foraging, bees exposed to these pesticide mixtures outlived control bees. Physiological analysis revealed that perturbations of the energetic metabolism preceded the altered behavior. In conclusion, we found that early-life exposure to low doses of pesticide mixtures can have long-term effects that translate into longer-lived but slower and less efficient bees. These surprising findings contrast with the commonly reported increase in bee mortality upon pesticide exposure, and demonstrate that exposure that may seem harmless (e.g., very low doses, pesticides not intended to kill insects) can have undesirable effects on non-target organisms.
KEYWORDS:
Foraging; Fungicides; Honey bee; Insecticides; Pollen; Survival

Association of erythrocyte n-3 polyunsaturated fatty acids with incident type 2 diabetes in a Chinese population.
Zheng JS, Lin JS, Dong HL, Zeng FF, Li D, Song Y, Chen YM.
Clin Nutr. 2018 Sep 26. pii: S0261-5614(18)32456-7. doi: 10.1016/j.clnu.2018.09.018. [Epub ahead of print]
PMID: 30309708
Abstract
BACKGROUND & AIMS:
The association between circulating n-3 polyunsaturated fatty acid (PUFA) biomarkers and incident type 2 diabetes in Asian populations remains unclear. We aimed to examine the association of erythrocyte n-3 PUFA with incident type 2 diabetes in a Chinese population.
METHODS:
A total of 2671 participants, aged 40-75 y, free of type 2 diabetes at baseline, were included in the present analysis. Incident type 2 diabetes cases (n = 213) were ascertained during median follow-up of 5.6 years. Baseline erythrocyte fatty acids were measured by gas chromatography. We used multivariable Cox regression models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of type 2 diabetes across quartiles of erythrocyte n-3 PUFA.
RESULTS:
After adjustment for potential confounders, HRs (95% CIs) of type 2 diabetes were 0.68 (0.47, 1.00), 0.77 (0.52, 1.15), and 0.63 (0.41, 0.95) in quartiles 2-4 of docosapentaenoic acid (C22:5n-3) (P-trend = 0.07), compared with quartile 1; and 1.08 (0.74, 1.60), 1.03 (0.70, 1.51), and 0.57 (0.38, 0.86) for eicosapentaenoic acid (C20:5n-3) (P-trend = 0.007). No association was found for docosahexaenoic acid (C22:6n-3) or alpha-linolenic acid (C18:3n-3).
CONCLUSIONS:
Erythrocyte n-3 PUFA from marine sources (C22:5n-3 and C20:5n-3), as biomarkers of dietary marine n-3 PUFA, were inversely associated with incident type 2 diabetes in this Chinese population. Future prospective investigations in other Asian populations are necessary to confirm our findings.
KEYWORDS:
Cohort study; Erythrocyte; Fatty acids; Prospective association; Type 2 diabetes

Intake of vegetables, fruit, and fish is beneficial for Age-related Macular Degeneration.
de Koning-Backus APM, Buitendijk GHS, Kiefte-de Jong JC, Colijn JM, Hofman A, Vingerling JR, Haverkort EB, Franco OH, Klaver CCW.
Am J Ophthalmol. 2018 Oct 9. pii: S0002-9394(18)30578-6. doi: 10.1016/j.ajo.2018.09.036. [Epub ahead of print]
PMID: 30312575
Abstract
PURPOSE:
What patients should eat to reduce their risk of age-related macular degeneration (AMD) is still unclear. We investigated the effect of a diet recommended by Health Councils on AMD.
DESIGN:
Prospective population-based cohort study.
METHODS:
4202 participants from the Rotterdam Study aged 55+ years, free of AMD at baseline, were included and followed up for 9.1±5.8 years. Incident AMD was graded on fundus photographs. Dietary data were collected using a validated 170-item food frequency questionnaire, and food intakes were categorized into food patterns based on guidelines from Health Councils. Associations with incident AMD were analyzed using Cox-proportional hazards models, and adjusted for age, sex, total energy intake, smoking, body mass index, hypertension, education, and income.
RESULTS:
A total of 754 persons developed incident AMD. Intake of the recommended amounts of vegetables (≥200gr/day), fruit (2x/day), and fish (2x/week) was 30.6%, 54.9% and 12.5%, respectively. In particular the intake of fish (2x/week) decreased the risk of incident AMD; hazard ratio (HR) 0.76 [95% Confidence Interval (CI) 0.60-0.97]). Intake of the recommended amounts of all three food groups was only 3.7%, but adherence to this pattern showed a further reduction of the risk of incident AMD (HR 0.58 [95%CI 0.36-0.93]). Younger age, higher income, and nonsmoking were associated with this food pattern, but risk lowering effects remained significant after additional adjustment for these factors.
CONCLUSION:
A diet of 200 grams of vegetables/day, 2x fruit/day, and 2x fish/week is associated with a significantly reduced risk of AMD.

[AlPater]

When scientists want their data fudged and why you should care
Some statisticians have been asked to falsify significance of research results, new study finds
Kelly Crowe · CBC News · Posted: Oct 13, 2018
https://www.cbc.ca/news/health/second-opinion-scientists-data-fudging-1.4861556
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Researcher Requests for Inappropriate Analysis and Reporting: A U.S. Survey of Consulting Biostatisticians.
Wang MQ, Yan AF, Katz RV.
Ann Intern Med. 2018 Oct 9. doi: 10.7326/M18-1230. [Epub ahead of print]
PMID: 30304365
Abstract
BACKGROUND:
Inappropriate analysis and reporting of biomedical research remain a problem despite advances in statistical methods and efforts to educate researchers.
OBJECTIVE:
To determine the frequency and severity of requests biostatisticians receive from researchers for inappropriate analysis and reporting of data during statistical consultations.
DESIGN:
Online survey.
SETTING:
United States.
PARTICIPANTS:
A randomly drawn sample of 522 American Statistical Association members self-identifying as consulting biostatisticians.
MEASUREMENTS:
The Bioethical Issues in Biostatistical Consulting Questionnaire soliciting reports about the frequency and perceived severity of specific requests for inappropriate analysis and reporting.
RESULTS:
Of 522 consulting biostatisticians contacted, 390 provided sufficient responses: a completion rate of 74.7%. The 4 most frequently reported inappropriate requests rated as "most severe" by at least 20% of the respondents were, in order of frequency, removing or altering some data records to better support the research hypothesis; interpreting the statistical findings on the basis of expectation, not actual results; not reporting the presence of key missing data that might bias the results; and ignoring violations of assumptions that would change results from positive to negative. These requests were reported most often by younger biostatisticians.
LIMITATIONS:
The survey provides information on the reported frequency of inappropriate requests but not on how such requests were handled or whether the requests reflected researchers' maleficence or inadequate knowledge about statistical and research methods. In addition, other inappropriate requests may have been made that were not prespecified in the survey.
CONCLUSION:
This survey suggests that researchers frequently make inappropriate requests of their biostatistical consultants regarding the analysis and reporting of their data. Understanding the reasons for these requests and how they are handled requires further study.

[AlPater]

Protein malnutrition mitigates the effects of a high-fat diet on glucose homeostasis in mice.
Branco RCS, Camargo RL, Batista TM, Vettorazzi JF, Lubaczeuski C, Bomfim LHM, Silveira LR, Boschero AC, Zoppi CC, Carneiro EM.
J Cell Physiol. 2018 Oct 14. doi: 10.1002/jcp.27361. [Epub ahead of print]
PMID: 30317568
Abstract
Nutrient malnutrition, during the early stages of development, may facilitate the onset of metabolic diseases later in life. However, the consequences of nutritional insults, such as a high-fat diet (HFD) after protein restriction, are still controversial. We assessed overall glucose homeostasis and molecular markers of mitochondrial function in the gastrocnemius muscle of protein-restricted mice fed an HFD until early adulthood. Male C57BL/6 mice were fed a control (14% protein-control diet) or a protein-restricted (6% protein-restricted diet) diet for 6 weeks. Afterward, mice received an HFD or not for 8 weeks (mice fed a control diet and HFD [CH] and mice fed a protein-restricted diet and HFD [RH]). RH mice showed lower weight gain and fat accumulation and did not show an increase in fasting plasma glucose and insulin levels compared with CH mice. RH mice showed higher energy expenditure, increased citrate synthase, peroxisome-proliferator-activated receptor gamma coactivator 1-alpha protein content, and higher levels of malate and α-ketoglutarate compared with CH mice. Moreover, RH mice showed increased AMPc-dependent kinase and acetyl coenzyme-A (CoA) carboxylase phosphorylation, lower intramuscular triacylglycerol content, and similar malonyl-CoA levels. In conclusion, protein undernourishment after weaning does not potentiate fat accumulation and insulin resistance in adult young mice fed an HFD. This outcome seems to be associated with increased skeletal muscle mitochondrial oxidative capacity and reduced lipids accumulation.
KEYWORDS:
fat-enriched diet; gastrocnemius; insulin sensitivity; protein restriction

Major trauma and acceleration of the ageing process.
Sullivan J, Mirbahai L, Lord JM.
Ageing Res Rev. 2018 Oct 11. pii: S1568-1637(18)30187-9. doi: 10.1016/j.arr.2018.10.001. [Epub ahead of print] Review.
PMID: 30316759
http://sci-hub.tw/http://www.sciencedirect.com/science/article/pii/S1568163718301879
Abstract
It is well established that numerous factors can affect the rate at which we age biologically. Diet, physical activity, lifestyle and our genes all play a major role in influencing the ageing trajectory and longevity. Major trauma affects millions globally, is the major cause of death in young adults and could influence ageing processes but has largely been ignored by biogenterologists. The long-term health consequences of physical trauma are well known in the medical community, how trauma effects the ageing process at a molecular level is not. It has long been difficult to assess ageing trajectories due to the absence of a biomarker of biological rather than chronological age. Recent advances in epigenetics have helped by identifying specific DNA methylation sites as good indicators of biological age. Recent investigations into the impact of psychological trauma and the associated physical stress on accelerating ageing as measured by epigenetic drift are promising. The physical and metabolic stress which is synonymous with physical trauma may also accelerate the ageing process. We suggest that long term epigenetic profiling is required to understand to what degree the ageing trajectory is altered by trauma, which will in turn add support for the development of novel therapies to improve health outcomes for survivors of traumatic injury.
KEYWORDS:
DNA methylation; ageing; epigenetic; injury; trauma
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[Don't drink and drive: https://www.archives-pmr.org/article/S0003-9993(13)00532-7/pdf .]

Searching for longevity hotspots in Denmark.
Hansen AV, Mortensen LH, Westendorp R.
Aging (Albany NY). 2018 Oct 13. doi: 10.18632/aging.101579. [Epub ahead of print]
PMID: 30317223
Abstract
While existing research on regions with high prevalence of centenarians has focused on selected candidate geographical regions, we explore the existence of hotspots in the whole of Denmark.We performed a Kulldorff spatial scan, searching for regions of birth, and of residence at age 71, where an increased percentage of the cohort born 1906-1915 became centenarians. We then compared mortality hazards for these regions to the rest of the country.We found a birth hotspot of 222 centenarians, 1.37 times more than expected, centered on a group of rural islands. Lower mortality hazards from age 71 onwards were confined to those born within the hotspot and persisted over a period of at least 30 years. At age 71, we found two residence-based hotspots of 348 respectively 238 centenarians, 1.46 and 1.44 times the expected numbers. One hotspot, located in high-income suburbs of the Danish capital, seems driven by selective in-migration of low-mortality individuals. The other hotspot seems driven by selective migration and lower morality among those born and residing in the hotspot.Thus, Danish centenarian hotspots do exist. The locations and interpretation depend on whether we look at place of birth or of residence late in life.
KEYWORDS:
Denmark; centenarian rate; cluster detection; longevity

Association between lifestyle risk factors and incident hypertension among middle-aged and older Australians.
Nguyen B, Bauman A, Ding D.
Prev Med. 2018 Oct 11. pii: S0091-7435(18)30312-8. doi: 10.1016/j.ypmed.2018.10.007. [Epub ahead of print]
PMID: 30316880
Abstract
This study aimed to examine the association between individual and combined lifestyle risk factors and the incidence of hypertension 1) in middle-aged and older Australians, and 2) to compare findings in men and women. A sample of 32,393 adults aged ≥45 years from New South Wales completed baseline (2006-2008) and follow-up (2010) questionnaires. Self-reported incident hypertension was defined as not having physician-diagnosed hypertension nor taking antihypertensive medications at baseline and reporting a diagnosis/treatment of hypertension at follow-up. High-risk categories for six lifestyle risk factors were defined as: a BMI ≥ 25 kg/m2, physical activity levels <150 min/week, consuming ≥14 alcohol drinks/week, being a current smoker, consuming <2 fruit and/or <3 vegetable serves/day, and being at high risk of psychological distress (Kessler-10 score ≥ 22). The association between baseline risk factors and incident hypertension was examined using logistic regression models, adjusted for socio-demographic, medical and lifestyle risk factors. After 2.7 (SD: 0.9) years of follow-up, 17.1% developed hypertension. Compared to low-risk categories, high BMI (AOR [95% CI]: 1.99 [1.85, 2.13]), high alcohol intake (1.58 [1.44, 1.73]), low physical activity levels (1.17 [1.07, 1.27]) and being a current smoker (1.15 [1.0, 1.31]) were associated with a higher incidence of hypertension in the overall sample, with similar associations in men and women. The number of high-risk lifestyle factors was positively associated with higher odds of developing hypertension in the overall sample, men and women; with a stronger association in middle-aged men. Adopting a low-risk lifestyle may prevent hypertension among middle-aged and older adults.
KEYWORDS:
Blood pressure; Hypertension; Lifestyle; Prospective studies; Risk factors

Broccoli consumption affects the human gastrointestinal microbiota.
Kaczmarek JL, Liu X, Charron CS, Novotny JA, Jeffery EH, Seifried HE, Ross SA, Miller MJ, Swanson KS, Holscher HD.
J Nutr Biochem. 2018 Sep 21;63:27-34. doi: 10.1016/j.jnutbio.2018.09.015. [Epub ahead of print]
PMID: 30317146
Abstract
The human gastrointestinal microbiota is increasingly linked to health outcomes; however, our understanding of how specific foods alter the microbiota is limited. Cruciferous vegetables such as broccoli are a good source of dietary fiber and phytonutrients, including glucosinolates, which can be metabolized by gastrointestinal microbes. This study aimed to determine the impact of broccoli consumption on the gastrointestinal microbiota of healthy adults. A controlled feeding, randomized, crossover study consisting of two 18-day treatment periods separated by a 24-day washout was conducted in healthy adults (n=18). Participants were fed at weight maintenance with the intervention period diet including 200 g of cooked broccoli and 20 g of raw daikon radish per day. Fecal samples were collected at baseline and at the end of each treatment period for microbial analysis. Beta diversity analysis indicated that bacterial communities were impacted by treatment (P=.03). Broccoli consumption decreased the relative abundance of Firmicutes by 9% compared to control (P=.05), increased the relative abundance of Bacteroidetes by 10% compared to control (P=.03) and increased Bacteroides by 8% relative to control (P=.02). Furthermore, the effects were strongest among participants with body mass index <26 kg/m2, and within this group, there were associations between bacterial relative abundance and glucosinolate metabolites. Functional prediction revealed that broccoli consumption increased the pathways involved in the functions of the endocrine system (P=.05), transport and catabolism (P=.04), and energy metabolism (P=.01). These results reveal that broccoli consumption affects the composition and function of the human gastrointestinal microbiota.
KEYWORDS:
Bacteroides; Brassica vegetables; Cruciferous vegetables; Glucosinolates; Microbiome

[AlPater]

Diabetes mellitus, blood glucose and the risk of heart failure: A systematic review and meta-analysis of prospective studies.
Aune D, Schlesinger S, Neuenschwander M, Feng T, Janszky I, Norat T, Riboli E.
Nutr Metab Cardiovasc Dis. 2018 Jul 25. pii: S0939-4753(18)30230-8. doi: 10.1016/j.numecd.2018.07.005. [Epub ahead of print]
PMID: 30318112
Abstract
BACKGROUND AND AIM:
The strength of the association between diabetes and risk of heart failure has differed between previous studies and the available studies have not been summarized in a meta-analysis. We therefore quantified the association between diabetes and blood glucose and heart failure in a systematic review and meta-analysis.
METHODS AND RESULTS:
PubMed and Embase databases were searched up to May 3rd 2018. Prospective studies on diabetes mellitus or blood glucose and heart failure risk were included. A random effects model was used to calculate summary relative risks (RRs) and 95% confidence intervals (CIs). Seventy seven studies were included. Among the population-based prospective studies, the summary RR for individuals with diabetes vs. no diabetes was 2.06 (95% CIs: 1.73-2.46, I2 = 99.8%, n = 30 studies, 401495 cases, 21416780 participants). The summary RR was 1.23 (95% CI: 1.15-1.32, I2 = 78.2%, n = 10, 5344 cases, 91758 participants) per 20 mg/dl increase in blood glucose and there was evidence of a J-shaped association with nadir around 90 mg/dl and increased risk even within the pre-diabetic blood glucose range. Among the patient-based studies the summary RR was 1.69 (95% CI: 1.57-1.81, I2 = 85.5%, pheterogeneity<0.0001) for diabetes vs. no diabetes (n = 41, 100284 cases and >613925 participants) and 1.25 (95% CI: 0.89-1.75, I2 = 95.6%, pheterogeneity<0.0001) per 20 mg/dl increase in blood glucose (1016 cases, 34309 participants, n = 2). In the analyses of diabetes and heart failure there was low or no heterogeneity among the population-based studies that adjusted for alcohol intake and physical activity and among the patient-based studies there was no heterogeneity among studies with ≥10 years follow-up.
CONCLUSIONS:
These results suggest that individuals with diabetes are at an increased risk of developing heart failure and there is evidence of increased risk even within the pre-diabetic range of blood glucose.
KEYWORDS:
Blood glucose; Diabetes mellitus; Heart failure; Meta-analysis; Systematic review

The Role of Lifestyle Factors and Sleep Duration for Late-Onset Dementia: A Cohort Study.
Larsson SC, Wolk A.
J Alzheimers Dis. 2018 Oct 3. doi: 10.3233/JAD-180529. [Epub ahead of print]
PMID: 30320581
Abstract
BACKGROUND:
The role of lifestyle factors and sleep for dementia is uncertain.
OBJECTIVE:
To examine the associations of major lifestyle factors and sleep duration with risk of late-onset dementia.
METHODS:
We used data from a population-based cohort of 28,775 Swedish adults who were ≥65 years of age and completed a questionnaire about lifestyle and other modifiable factors in the autumn of 1997. Dementia cases were ascertained by linkage with the Swedish National Patient Register.
RESULTS:
During a mean follow-up of 12.6 years, dementia was diagnosed among 3,755 participants (mean age at diagnosis 83.2±5.1 years). There were no associations of an overall healthy diet (defined by a modified Dietary Approaches to Stop Hypertension Diet score or a Mediterranean diet score), alcohol and coffee consumption, or physical activity with dementia incidence. Compared with never smokers, dementia risk was increased in former and current smokers (hazard ratio [95% confidence interval] = 1.13 [1.04-1.23] and 1.10 [1.00-1.21], respectively). Extended time of sleep (>9 h per night) was associated with an increased risk of dementia. However, this association appeared to be related to a reverse causation effect since the association did not remain after exclusion of cases diagnosed within the first five or ten years of follow-up.
CONCLUSIONS:
This study found no evidence that major lifestyle factors, aside from smoking, or sleep duration influence the risk of dementia.
KEYWORDS:
Cohort studies; dementia; diet; lifestyle; prospective studies; sleep

The effects of whole-grain compared with refined wheat, rice, and rye on the postprandial blood glucose response: a systematic review and meta-analysis of randomized controlled trials.
Musa-Veloso K, Poon T, Harkness LS, O'Shea M, Chu Y.
Am J Clin Nutr. 2018 Oct 1;108(4):759-774. doi: 10.1093/ajcn/nqy112.
PMID: 30321274
https://sci-hub.tw/10.1093/ajcn/nqy112
Abstract
BACKGROUND:
Whole grains are often referred to collectively, despite differences in their composition, physical structure, processing, and potential health benefits.
OBJECTIVE:
The aim of this study was to compare the postprandial blood glucose response of whole-grain with refined wheat, rice, or rye, while controlling for the food delivery matrix and the processing of the grain (e.g., grinding, germination).
DESIGN:
Eleven electronic databases were systematically searched to identify studies published up to and including November 2017. Randomized controlled trials comparing the effects of whole-grain wheat, rice, or rye with those of each grain's refined counterpart on postprandial blood glucose area under the curve (AUC) were included. Pooled effect sizes were computed by using the difference in the blood glucose AUC after the consumption of the whole compared with the refined grain.
RESULTS:
Twenty publications were included, with 10, 14, and 5 strata (or active-control comparisons) on whole-grain wheat, rice, and rye, respectively. The consumption of ground (wholemeal) wheat, compared with white wheat, was not associated with a significant reduction in blood glucose AUC (-6.7 mmol/L ⋅ min; 95% CI: -25.1, 11.7 mmol/L ⋅ min; P = 0.477). The consumption of wholemeal rye, compared with endosperm rye, was not associated with a significant reduction in blood glucose AUC (-5.5 mmol/L ⋅ min; 95% CI: -24.8, 13.8 mmol/L ⋅ min; P = 0.576). The consumption of intact (whole-grain) rice, compared with white rice, was associated with a significant reduction in blood glucose AUC (-40.5 mmol/L ⋅ min; 95% CI: -59.6, -21.3 mmol/L ⋅ min; P < 0.001).
CONCLUSIONS:
Compared with white rice, whole-grain rice significantly attenuates the postprandial blood glucose response. In most of the studies on wheat and rye, the postprandial blood glucose responses to foods formulated with wholemeal compared with refined flours were compared. Whether reductions in the blood glucose AUC can be achieved with whole-grain (as opposed to wholemeal) wheat and rye requires further investigation.

Edited October 16, 2018 by AlPater

[AlPater]

Metabolomics identifies increases in the acylcarnitine profiles in the plasma of overweight subjects in response to mild weight loss: a randomized, controlled design study.
Kang M, Yoo HJ, Kim M, Kim M, Lee JH.
Lipids Health Dis. 2018 Oct 15;17(1):237. doi: 10.1186/s12944-018-0887-1.
PMID: 30322392
https://lipidworld.biomedcentral.com/track/pdf/10.1186/s12944-018-0887-1
Abstract
BACKGROUND:
Using metabolomics technique to analyze the response to a dietary intervention generates valuable information concerning the effects of the prescribed diet on metabolic regulation. To determine whether low calorie diet (LCD)-induced weight reduction causes changes in plasma metabolites and metabolic characteristics.
METHODS:
Overweight subjects consumed a LCD (n = 47) or a weight maintenance diet (control, n = 50) in a randomized, controlled design study with a 12-week clinical intervention period. Plasma samples were analyzed using an UPLC-LTQ-Orbitrap MS.
RESULTS:
The 12-week LCD intervention resulted in significant mild weight loss, with an 8.3% and 10.6% reduction observed in the visceral fat area (VFA) at the level of the lumbar vertebrae L1 and L4, respectively. The LCD group showed a significant increase in the mean change of serum free fatty acids compared to the control group. In the LCD group, we observed a significant increase in the acylcarnitine (AC) levels, including hexanoylcarnitine, L-octanoylcarnitine, 9-decenoylcarnitine, trans-2-dodecenoylcanitine, dodecanoylcarnitine, 3,5-tetradecadiencarnitine, cis-5-tetradecenoylcarnitine, 9,12-hexadecadienoylcarnitine, and 9-hexadecenoylcarnitne at the 12-week follow-up assessment. When the plasma metabolite changes from baseline were compared between the control and LCD groups, the LCD group showed significant increases in hexanoylcarnitine, L-octanoylcarnitine, trans-2-dodecenoylcanitine, and 3,5-tetradecadiencarnitine than the control group. Additionally, the changes in these ACs in the LCD group strongly negatively correlated with the changes in the VFA at L1 and/or L4.
CONCLUSION:
Mild weight loss from 12-week calorie restriction increased the plasma levels of medium- and long-chain ACs. These changes were coupled with a decrease in VFA and an increase in free fatty acids.
KEYWORDS:
Acylcarnitine; Low calorie diet; Metabolomics; Mild weight loss; Visceral fat area

Social Isolation and Mortality in US Black and White Men and Women.
Alcaraz KI, Eddens KS, Blase JL, Diver WR, Patel AV, Teras LR, Stevens VL, Jacobs EJ, Gapstur SM.
Am J Epidemiol. 2018 Oct 16. doi: 10.1093/aje/kwy231. [Epub ahead of print]
PMID: 30325407
Abstract
Social isolation is associated with higher mortality in studies of mostly white adults, yet associations among black adults is unclear. This prospective cohort study evaluated whether associations of social isolation with all-cause, cardiovascular disease and cancer mortality differ by race and sex. Adults enrolled into Cancer Prevention Study-II in 1982/1983 were followed for mortality through 2012 (n = 580,182). Sex- and race-specific multivariable-adjusted hazard ratios and 95% confidence intervals were estimated for associations of a five-point social isolation score with risk of death. Social isolation was associated with all-cause mortality in all subgroups (P-trend ≤ 0.005); for the most versus the least isolated, the hazard ratios (95% confidence intervals) were 2.34 (1.58, 3.46) and 1.60 (1.41, 1.82) among black and white men, respectively (P-interaction = 0.40), and 2.13 (1.44, 3.15) and 1.84 (1.68, 2.01) among black and white women, respectively (P-interaction = 0.89). The association did not differ between black men and women (P-interaction = 0.33) but was slightly stronger in white women than white men (P-interaction = 0.01). Social isolation was associated with cardiovascular disease mortality in each subgroup (P-trend < 0.03) but with cancer mortality only among whites (P-trend < 0.0001). Subgroup differences in the influence of specific social isolation components were identified. Identifying and intervening with socially isolated adults could improve health outcomes.

An association of urinary sodium-potassium ratio with insulin resistance among Korean adults.
Park YM, Kwock CK, Park S, Eicher-Miller HA, Yang YJ.
Nutr Res Pract. 2018 Oct;12(5):443-448. doi: 10.4162/nrp.2018.12.5.443. Epub 2018 Sep 28.
PMID: 30323912

Abstract
BACKGROUND/OBJECTIVES:
This study was conducted to investigate the effects of sodium-potassium ratio on insulin resistance and sensitivity in Korean adults.
SUBJECTS/METHODS:
Subjects were 3,722 adults (1,632 men and 2,090 women) aged 40-69 years participating in the Korean genome and epidemiology study_Ansan and Ansung study. Insulin resistance was assessed using homeostasis model assessment of insulin resistance (HoMA-IR) and fasting insulin, and insulin sensitivity was assessed by using the quantitative insulin sensitivity check index (QUICKI). The 24-h urinary sodium and potassium excretion were estimated from spot urinary samples using the Tanaka formula. The generalized linear model was applied to determine the association between urinary sodium-potassium ratio and insulin resistance.
RESULTS:
HoMA-IR (P-value = 0.029, P-trend = 0.008) and fasting insulin (P-value = 0.017, P-trend = 0.005) levels were positively associated with 24-h estimated urinary sodium-potassium ratio in the multivariable model. QUICKI was inversely associated with 24-h estimated urinary sodium-potassium ratio in all models (P-value = 0.0002, P-trend < 0.0001 in the multivariate model).
CONCLUSION:
The present study suggests that high sodium-potassium ratio is related to high insulin resistance and low insulin sensitivity. Decreasing sodium intake and increasing potassium intake are important for maintaining insulin sensitivity. Further studies are needed to confirm these findings in longitudinal studies.
KEYWORDS:
Sodium; insulin resistance; insulin sensitivity; potassium

Physical Activity and Association Between Frailty and All-Cause and Cardiovascular Mortality in Older Adults: Population-Based Prospective Cohort Study.
Higueras-Fresnillo S, Cabanas-Sánchez V, Lopez-Garcia E, Esteban-Cornejo I, Banegas JR, Sadarangani KP, Rodríguez-Artalejo F, Martinez-Gomez D.
J Am Geriatr Soc. 2018 Oct 16. doi: 10.1111/jgs.15542. [Epub ahead of print]
PMID: 30325012
Abstract
OBJECTIVES:
To examine the separate and joint association between physical activity and frailty and long-term all-cause and cardiovascular disease (CVD) mortality in older adults.
DESIGN:
Population-based prospective cohort study.
SETTING:
Cohort representative of the noninstitutionalized Spanish population.
PARTICIPANTS:
Individuals aged 60 and older (N=3,896) in 2000-01.
MEASUREMENTS:
Participants reported their physical activity using a validated instrument, and frailty was ascertained using the Fatigue, low Resistance, limitation in Ambulation, Illness and weight Loss (FRAIL) scale. Those with 0 frailty criteria were considered to be robust, with 1 or 2 criteria to be prefrail, and with 3 of more criteria to be frail. Participants were followed until 2014 to identify all-cause and CVD deaths. Associations were summarized using hazard ratios (HRs) and Cox regression after adjustment for main covariates.
RESULTS:
During a median 14 years of follow-up, 1,801 total deaths occurred, 672 from CVD. Compared with being robust, the multivariate hazard ratio (95% confidence interval) for all-cause mortality was 1.29 (1.14-1.45) in prefrail individuals, and 2.16 (1.82-2.58) in frail individuals (p-trend <.001). Compared with being physically inactive, being physically active was associated with a statistically significant 18% (1-32%), 28% (16-39%) and 39% (17-55%) lower all-cause mortality among robust, prefrail, and frail individuals, respectively (all p <.001). Compared with participants who were robust and physically active, those who were frail and inactive showed the highest all-cause mortality 2.45 (95%CI: 1.95-3.06); however, the hazard ratio (95% confidence interval) for all-cause mortality in frail individuals who were physically active was comparable to that in pre-frail and inactive participants: 1.70 (1.32-2.19) and 1.56 (1.34-1.82), respectively. Mortality of prefrail active participants was similar to that of robust inactive participants. Results were similar for CVD mortality.
CONCLUSION:
Physical activity might partly compensate for the greater mortality risk associated with frailty in old age.
KEYWORDS:
elderly; frailty; mortality; physical activity

Prolonging healthy aging: Longevity vitamins and proteins.
Ames BN.
Proc Natl Acad Sci U S A. 2018 Oct 15. pii: 201809045. doi: 10.1073/pnas.1809045115. [Epub ahead of print]
PMID: 30322941
https://sci-hub.tw/10.1073/pnas.1809045115
Abstract
It is proposed that proteins/enzymes be classified into two classes according to their essentiality for immediate survival/reproduction and their function in long-term health: that is, survival proteins versus longevity proteins. As proposed by the triage theory, a modest deficiency of one of the nutrients/cofactors triggers a built-in rationing mechanism that favors the proteins needed for immediate survival and reproduction (survival proteins) while sacrificing those needed to protect against future damage (longevity proteins). Impairment of the function of longevity proteins results in an insidious acceleration of the risk of diseases associated with aging. I also propose that nutrients required for the function of longevity proteins constitute a class of vitamins that are here named "longevity vitamins." I suggest that many such nutrients play a dual role for both survival and longevity. The evidence for classifying taurine as a conditional vitamin, and the following 10 compounds as putative longevity vitamins, is reviewed: the fungal antioxidant ergothioneine; the bacterial metabolites pyrroloquinoline quinone (PQQ) and queuine; and the plant antioxidant carotenoids lutein, zeaxanthin, lycopene, α- and β-carotene, β-cryptoxanthin, and the marine carotenoid astaxanthin. Because nutrient deficiencies are highly prevalent in the United States (and elsewhere), appropriate supplementation and/or an improved diet could reduce much of the consequent risk of chronic disease and premature aging.
KEYWORDS:
aging; essential minerals; nutrition; vitamins

A comparison of blood pressure indices as predictors of all-cause mortality among middle-aged men and women during 701,707 person-years of follow-up.
Rosenblad A.
J Hum Hypertens. 2018 Jul 10. doi: 10.1038/s41371-018-0085-7. [Epub ahead of print]
PMID: 29991703
Abstract
High systolic blood pressure (SBP) is often used as a measure of hypertension in epidemiological studies. Alternative blood pressure (BP) indices include diastolic blood pressure (DBP), pulse pressure (PP), mid-blood pressure (MBP) and mean arterial pressure (MAP). The present study compares the predictive ability for all-cause mortality (ACM) of these indices and the novel BP index mean proportional arterial pressure (MPAP), defined as the weighted mean of SBP and DBP where the weights are proportional to SBP's and DBP's contributions to the sum of SBP and DBP. Using a Swedish cohort of 32,238 middle-aged men and women, not being on antihypertensive treatment, examined in 1989-2000 and followed-up until March 9, 2017, the predictive abilities for ACM of SBP, DBP, PP, MBP, MAP and MPAP were compared using a likelihood-based R2-type measure for adjusted and unadjusted Cox regression models. Of the included participants (mean age 45.4 years, 48.2% men), 2936 (9.1%) died during a mean follow-up time of 21.8 years, equalling 701,707 person-years at risk. Higher BP were for all indices significantly associated with increased ACM. For all models, those including MPAP had the highest predictive ability, followed in turn by models including MBP, SBP, MAP, DBP and PP, respectively. The difference was significant for SBP, DBP and PP in unadjusted models and for PP in fully adjusted models. In conclusion, MPAP and MBP are the best predictors of ACM. Until the clinical usefulness of these indices has been evaluated, they may primarily be useful for epidemiological studies.

Edited October 17, 2018 by AlPater

[AlPater]

Unscrambling the relations of egg and meat consumption with type 2 diabetes risk.
Sabaté J, Burkholder-Cooley NM, Segovia-Siapco G, Oda K, Wells B, Orlich MJ, Fraser GE.
Am J Clin Nutr. 2018 Oct 16. doi: 10.1093/ajcn/nqy213. [Epub ahead of print]
PMID: 30329007
Abstract
BACKGROUND:
Meat intake is associated with increased risk of type 2 diabetes (T2D). It is not clear if egg intake is associated with T2D risk because purported associations may be due to concurrent consumption of eggs with meat.
OBJECTIVE:
Our aim was to differentiate any associations between meat and egg consumption and the risk of T2D.
DESIGN:
In this longitudinal study, 55,851 participants of the Adventist Health Study 2 who were free of diabetes provided demographic, anthropometric, and dietary data at baseline. Meat and egg intakes were assessed with a validated quantitative food-frequency questionnaire. Responses to 2 follow-up questionnaires determined incident T2D cases. Multivariate-adjusted logistic regression was used to determine relations between meat and egg intake and incident T2D.
RESULTS:
T2D cases identified during a mean 5.3 y of follow-up totaled 2772. Meat intake of >0 to <25 g/d, ≥25 to <70 g/d, and ≥70 g/d significantly increased the risk of T2D compared with no meat intake (OR: 1.29; 95% CI: 1.16, 1.44; OR: 1.42; 95% CI: 1.25, 1.61; and OR: 1.65; 95% CI: 1.39, 1.96, respectively; P-trend < 0.0001). Egg intake compared with no egg intake was not associated with T2D risk. A significant meat-egg interaction (P = 0.019) showed that within every category of egg intake, there was an incremental rise in T2D risk as meat intake increased. However, within categories of meat intake, increasing egg intake did not increase the risk of T2D except among nonmeat-eaters consuming ≥5 eggs/wk (OR: 1.52; 95% CI: 1.09, 2.12).
CONCLUSIONS:
Meat consumption, but not egg consumption, is independently associated with T2D risk. Egg intake seems not to increase T2D risk further with meat intake. Our findings suggest that the purported egg-T2D risk relation in US populations may be biased due to failure to investigate egg-meat interactions. Further investigations are needed to ascertain T2D risk among nonmeat-eaters with high egg intakes.

Advancing front of old-age human survival.
Zuo W, Jiang S, Guo Z, Feldman MW, Tuljapurkar S.
Proc Natl Acad Sci U S A. 2018 Oct 16. pii: 201812337. doi: 10.1073/pnas.1812337115. [Epub ahead of print]
PMID: 30327342
https://sci-hub.tw/10.1073/pnas.1812337115
Abstract
Old-age mortality decline has driven recent increases in lifespans, but there is no agreement about trends in the age pattern of old-age deaths. Some argue that old-age deaths should become compressed at advanced ages, others argue that old-age deaths should become more dispersed with age, and yet others argue that old-age deaths are consistent with little change in dispersion. However, direct analysis of old-age deaths presents unusual challenges: Death rates at the oldest ages are always noisy, published life tables must assume an asymptotic age pattern of deaths, and the definition of "old-age" changes as lives lengthen. Here we use robust percentile-based methods to overcome some of these challenges and show, for five decades in 20 developed countries, that old-age survival follows an advancing front, like a traveling wave. The front lies between the 25th and 90th percentiles of old-age deaths, advancing with nearly constant long-term shape but annual fluctuations in speed. The existence of this front leads to several predictions that we verify, e.g., that advances in life expectancy at age 65 y are highly correlated with the advance of the 25th percentile, but not with distances between higher percentiles. Our unexpected result has implications for biological hypotheses about human aging and for future mortality change.
KEYWORDS:
death percentiles; human mortality; old-age survival; survival front

Dietary Sodium Restriction Reduces Arterial Stiffness, Vascular TGF-β-Dependent Fibrosis and Marinobufagenin in Young Normotensive Rats.
Grigorova YN, Wei W, Petrashevskaya N, Zernetkina V, Juhasz O, Fenner R, Gilbert C, Lakatta EG, Shapiro JI, Bagrov AY, Fedorova OV.
Int J Mol Sci. 2018 Oct 15;19(10). pii: E3168. doi: 10.3390/ijms19103168.
PMID: 30326586
https://www.mdpi.com/1422-0067/19/10/3168/htm
Abstract
High salt (HS) intake stimulates the production of marinobufagenin (MBG), an endogenous steroidal Na/K-ATPase ligand, which activates profibrotic signaling. HS is accompanied by a blood pressure (BP) increase in salt-sensitive hypertension, but not in normotensive animals. Here, we investigated whether HS stimulates MBG production and activates transforming growth factor-beta (TGF-β) profibrotic signaling in young normotensive rats, and whether these changes can be reversed by reducing salt to a normal salt (NS) level. Three-month old male Sprague⁻Dawley rats received NS for 4 and 8 weeks (0.5% NaCl; NS4 and NS8), or HS for 4 and 8 weeks (4% NaCl; HS4 and HS8), or HS for 4 weeks followed by NS for 4 weeks (HS4/NS4), n = 8/group. Systolic BP (SBP), pulse wave velocity (PWV), MBG excretion, aortic collagen 1α2, collagen 4α1 and TGF-β, Smad2, Smad3, Fli-1 mRNA, and total collagen abundance were measured at baseline (BL), and on weeks 4 and 8. Statistical analysis was performed using one-way ANOVA. SBP was not affected by HS (125 ± 5 and 126 ± 6 vs. 128 ± 7 mmHg, HS4 and HS8 vs. BL, p > 0.05). HS increased MBG (164 ± 19 vs. 103 ± 19 pmol/24 h/kg, HS4 vs. BL, p < 0.05) and PWV (3.7 ± 0.2 vs. 2.7 ± 0.2 m/s, HS4 vs. NS4, p < 0.05). HS8 was associated with a further increase in MBG and PWV, with an increase in aortic Col1a2 80%), Col4a1 (50%), Tgfb1 (30%), Smad2 (30%) and Smad3 (45%) mRNAs, and aortic wall collagen (180%) vs. NS8 (all p < 0.05). NS following HS downregulated HS-induced factors: in HS4/NS4, the MBG level was 91 ± 12 pmol/24 h/kg (twofold lower than HS8, p < 0.01), PWV was 3.7 ± 0.3 vs. 4.7 ± 0.2 m/s (HS4/NS4 vs. HS8, p < 0.05), aortic wall Tgfb1, Col1a2, Col4a1, Smad2, Smad3 mRNAs, and collagen abundance were reversed by salt reduction to the BL levels (p < 0.05). HS was associated with an activation of TGF-β signaling, aortic fibrosis and aortic stiffness accompanied by an MBG increase in the absence of SBP changes in young normotensive rats. The reduction of dietary salt following HS decreased MBG, PWV, aortic wall collagen and TGF-β. Thus, HS-induced aortic stiffness in normotensive animals occurred in the context of elevated MBG, which may activate SMAD-dependent TGF-β pro-fibrotic signaling. This data suggests that a decrease in salt consumption could help to restore aortic elasticity and diminish the risk of cardiovascular disease by reducing the production of the pro-fibrotic factor MBG.
KEYWORDS:
Na/K-ATPase inhibitors; TGFβ1; aortic stiffness; cardiotonic steroids; collagen; high sodium chloride diet; marinobufagenin; pulse wave velocity; tissue fibrosis; transforming growth factor beta; vascular smooth muscle cells

Which Kinds of Foods Make Us Fat?
CreditCreditIllustration by Kelsey Dake
By Gretchen Reynolds
Sept. 25, 2018
https://www.nytimes.com/2018/09/25/well/eat/which-kinds-of-foods-make-us-fat.html?fallback=0&recId=1BkpxpdEOL1LyBewwP4A8dfrdZH&locked=0&geoContinent=NA&geoRegion=SK&recAlloc=contextual-bandit-home-geo&geoCountry=CA&blockId=home-living-vi&imp_id=950652061
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Dietary Fat, but Not Protein or Carbohydrate, Regulates Energy Intake and Causes Adiposity in Mice.
Hu S, Wang L, Yang D, Li L, Togo J, Wu Y, Liu Q, Li B, Li M, Wang G, Zhang X, Niu C, Li J, Xu Y, Couper E, Whittington-Davies A, Mazidi M, Luo L, Wang S, Douglas A, Speakman JR.
Cell Metab. 2018 Sep 4;28(3):415-431.e4. doi: 10.1016/j.cmet.2018.06.010. Epub 2018 Jul 12.
PMID: 30017356
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30392-9
Abstract
The impacts of different macronutrients on body weight regulation remain unresolved, with different studies suggesting increased dietary fat, increased carbohydrates (particularly sugars), or reduced protein may all stimulate overconsumption and drive obesity. We exposed C57BL/6 mice to 29 different diets varying from 8.3% to 80% fat, 10% to 80% carbohydrate, 5% to 30% protein, and 5% to 30% sucrose. Only increased dietary fat content was associated with elevated energy intake and adiposity. This response was associated with increased gene expression in the 5-HT receptors, and the dopamine and opioid signaling pathways in the hypothalamus. We replicated the core findings in four other mouse strains (DBA/2, BALB/c, FVB, and C3H). Mice regulate their food consumption primarily to meet an energy rather than a protein target, but this system can be over-ridden by hedonic factors linked to fat, but not sucrose, consumption.
KEYWORDS:
FGF signaling; energy regulation; fat intake; hedonic overdrive; hypothalamic hunger pathway; mTOR signaling; mice; obesity; protein leverage hypothesis; sucrose intake

Keto diet may protect against cognitive decline
Published Tuesday 16 October 2018
https://www.medicalnewstoday.com/articles/323345.php
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Ketogenic diet enhances neurovascular function with altered gut microbiome in young healthy mice
David Ma, Amy C. Wang, Ishita Parikh, Stefan J. Green, Jared D. Hoffman, George Chlipala, M. Paul Murphy, Brent S. Sokola, Björn Bauer, Anika M. S. Hartz & Ai-Ling Lin 
Scientific Reports volume 8, Article number: 6670 (2018)
https://www.nature.com/articles/s41598-018-25190-5
Abstract
Neurovascular integrity, including cerebral blood flow (CBF) and blood-brain barrier (BBB) function, plays a major role in determining cognitive capability. Recent studies suggest that neurovascular integrity could be regulated by the gut microbiome. The purpose of the study was to identify if ketogenic diet (KD) intervention would alter gut microbiome and enhance neurovascular functions, and thus reduce risk for neurodegeneration in young healthy mice (12–14 weeks old). Here we show that with 16 weeks of KD, mice had significant increases in CBF and P-glycoprotein transports on BBB to facilitate clearance of amyloid-beta, a hallmark of Alzheimer’s disease (AD). These neurovascular enhancements were associated with reduced mechanistic target of rapamycin (mTOR) and increased endothelial nitric oxide synthase (eNOS) protein expressions. KD also increased the relative abundance of putatively beneficial gut microbiota (Akkermansia muciniphila and Lactobacillus), and reduced that of putatively pro-inflammatory taxa (Desulfovibrio and Turicibacter). We also observed that KD reduced blood glucose levels and body weight, and increased blood ketone levels, which might be associated with gut microbiome alteration. Our findings suggest that KD intervention started in the early stage may enhance brain vascular function, increase beneficial gut microbiota, improve metabolic profile, and reduce risk for AD.

No sweat required: Team finds hypertension treatment that mimics effect of exercise
October 16, 2018
https://medicalxpress.com/news/2018-10-required-team-hypertension-treatment-mimics.html
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Salt-Responsive Metabolite, β-Hydroxybutyrate, Attenuates Hypertension
Saroj Chakraborty, Sarah Galla, Xi Cheng, Ji-Youn Yeo, Blair Mell, Vishal Singh, BengSan Yeoh, Piu Saha, Anna V. Mathew, Matam Vijay-Kumar, Bina Joe
Cell Reports VOLUME 25, ISSUE 3, P677-689.E4, OCTOBER 16, 2018 doi.org/10.1016/j.celrep.2018.09.058
https://www.cell.com/cell-reports/fulltext/S2211-1247(18)31503-1
Highlights
The liver contributes to blood pressure regulation via ketone body production
High salt diet reduces the ketone body beta-hydroxybutyrate (βOHB)
Reduced βOHB results in increased renal Nlrp3 inflammasome activity in hypertension
Nutritional intervention with the βOHB precursor 1,3-butanediol lowers hypertension
Summary
Dietary salt reduction and exercise are lifestyle modifications for salt-sensitive hypertensives. While exercise has prominent metabolic effects, salt has an adverse effect on metabolic syndrome, of which hypertension is a hallmark. We hypothesized that dietary salt impacts metabolism in a salt-sensitive model of hypertension. An untargeted metabolomic approach demonstrates lower circulating levels of the ketone body, beta-hydroxybutyrate (βOHB), in high salt-fed hypertensive rats. Despite the high salt intake, specific rescue of βOHB levels by nutritional supplementation of its precursor, 1,3-butanediol, attenuates hypertension and protects kidney function. This beneficial effect of βOHB was likely independent of gut-microbiotal and Th17-mediated effects of salt and instead facilitated by βOHB inhibiting the renal Nlrp3 inflammasome. The juxtaposed effects of dietary salt and exercise on salt-sensitive hypertension, which decrease and increase βOHB respectively, indicate that nutritional supplementation of a precursor of βOHB provides a similar benefit to salt-sensitive hypertension as exercise.

[AlPater]

Effect of Bacillus subtilis C-3102 on bone mineral density in healthy postmenopausal Japanese women: a randomized, placebo-controlled, double-blind clinical trial.
Takimoto T, Hatanaka M, Hoshino T, Takara T, Tanaka K, Shimizu A, Morita H, Nakamura T.
Biosci Microbiota Food Health. 2018;37(4):87-96. doi: 10.12938/bmfh.18-006. Epub 2018 Jun 16.
PMID: 30370192
https://www.jstage.jst.go.jp/article/bmfh/advpub/0/advpub_18-006/_pdf
Abstract
Gut microbiota influence the host immune system and are associated with various diseases. In recent years, postmenopausal bone loss has been suggested to be related to gut microbiota. In the present study, we investigated the treatment effect of the probiotic Bacillus subtilis C-3102 (C-3102) on bone mineral density (BMD) and its influence on gut microbiota in healthy postmenopausal Japanese women. Seventy-six healthy postmenopausal Japanese women were treated with a placebo or C-3102 spore-containing tablets for 24 weeks. When compared with the placebo, C-3102 significantly increased total hip BMD (placebo = 0.83 ± 0.63%, C-3102 = 2.53 ± 0.52%, p=0.043). There was a significant group-by-time interaction effect for urinary type I collagen cross-linked N-telopeptide (uNTx) (p=0.033), a marker of bone resorption. Specifically, the C-3102 group showed significantly lower uNTx when compared with the placebo group at 12 weeks of treatment (p=0.015). In addition, in the C-3102 group, there was a trend towards a decrease in the bone resorption marker tartrate-resistant acid phosphatase isoform 5b (TRACP-5b) when compared with the placebo group at 12 weeks of treatment (p=0.052). The relative abundance of genus Bifidobacterium significantly increased at 12 weeks of treatment compared with the baseline in the C-3102 group. The relative abundance of genus Fusobacterium was significantly decreased in the C-3102 group at 12 and 24 weeks of treatment compared with the baseline. These data suggested that C-3102 improves BMD by inhibiting bone resorption and modulating gut microbiota in healthy postmenopausal women.
KEYWORDS:
bone; microbiota; osteoporosis; probiotics

Intake of fermented and non-fermented dairy products and risk of incident CHD: the Kuopio Ischaemic Heart Disease Risk Factor Study.
Koskinen TT, Virtanen HEK, Voutilainen S, Tuomainen TP, Mursu J, Virtanen JK.
Br J Nutr. 2018 Oct 29:1-10. doi: 10.1017/S0007114518002830. [Epub ahead of print]
PMID: 30370878
Abstract
Recent dairy product studies have suggested that fermented rather than non-fermented dairy products might provide benefits on cardiovascular health, but the evidence is inconclusive. Therefore, we investigated whether fermented and non-fermented dairy products have distinct associations with the risk of incident CHD in a population with high dairy product intake. The present study included a total of 1981 men, aged 42-60 years, from the Kuopio Ischaemic Heart Disease Risk Factor Study, with no CHD at baseline. Dietary intakes were assessed with instructed 4-d food records. We used Cox's proportional hazards regression model to estimate the associations with the risk of CHD. Fatal and non-fatal CHD events were ascertained from national registries. During a mean follow-up of 20·1 years, 472 CHD events were recorded. Median intakes were 105 g/d for fermented (87 % low-fat products) and 466 g/d for non-fermented dairy products (60 % low-fat products). After adjusting for potential confounders, those in the highest (v. lowest) intake quartile of fermented dairy products had 27 % (95 % CI 5, 44; P-trend=0·02) lower risk of CHD. In contrast, those in the highest intake quartile of non-fermented dairy products had 52 % (95 % CI 13, 104; P-trend=0·003) higher risk of CHD. When analysed based on fat content, low-fat (<3·5 % fat) fermented dairy product intake was associated with lower risk (hazard ratio in the highest quartile=0·74; 95 % CI 0·57, 0·97; P-trend=0·03), but high-fat fermented dairy and low-fat or high-fat non-fermented dairy products had no association. These results suggest that fermented and non-fermented dairy products can have opposite associations with the risk of CHD.
KEYWORDS:
AR absolute risk; HR hazard ratio; KIHD Kuopio Ischaemic Heart Disease Risk Factor Study; CHD; Dairy products; Fermented dairy products; Finnish men; Prospective cohort studies

Effect of garlic supplementation on serum C-reactive protein level: A systematic review and meta-analysis of randomized controlled trials.
Taghizadeh M, Hamedifard Z, Jafarnejad S.
Phytother Res. 2018 Oct 29. doi: 10.1002/ptr.6225. [Epub ahead of print] Review.
PMID: 30370629
Abstract
The present study was designed to systematically review randomized controlled trials (RCTs) that report on the effects of garlic supplementation on serum C-reactive protein (CRP) levels. We conducted a literature search of Scopus, PubMed, Cochrane Library, and Google Scholar up to January 2018. Weighted mean differences (WMD) were estimated for net change in serum CRP. Subgroup analyses were also performed by duration of study, dose of supplementation, baseline CRP level, and the quality of studies. From 438 articles found and screened in our initial search, nine RCTs with the sum of total sample size of 363 were included in the meta-analysis. Compared with the controls, garlic intake significantly reduced the concentrations of serum CRP by 0.8 mg/L (95% CI [-1.5, -0.1], p = 0.02) with the evidence of heterogeneity among studies. Subgroup analyses showed that garlic significantly lowered CRP by 0.82 mg/L (95% CI [-1.02, -0.62], p < 0.001) among studies with a daily garlic dose ≥1,200 mg/day and by 2.44 mg/L (95% CI [-4.02, -0.87], p = 0.002) among studies with baseline CRP ≥2 mg/L. Current data confirmed that garlic supplementation would reduce serum CRP levels. However, the changes were related to the supplemental doses and baseline levels of serum CRP.
KEYWORDS:
C-reactive protein; garlic; meta-analysis; randomized controlled trial

Self-Reported Sleep Duration and Quality and Cardiovascular Disease and Mortality: A Dose-Response Meta-Analysis.
Kwok CS, Kontopantelis E, Kuligowski G, Gray M, Muhyaldeen A, Gale CP, Peat GM, Cleator J, Chew-Graham C, Loke YK, Mamas MA.
J Am Heart Assoc. 2018 Aug 7;7(15):e008552. doi: 10.1161/JAHA.118.008552.
PMID: 30371228
https://www.ahajournals.org/doi/10.1161/JAHA.118.008552
Abstract
Background There is growing evidence that sleep duration and quality may be associated with cardiovascular harm and mortality. Methods and Results We conducted a systematic review, meta-analysis, and spline analysis of prospective cohort studies that evaluate the association between sleep duration and quality and cardiovascular outcomes. We searched MEDLINE and EMBASE for these studies and extracted data from identified studies. We utilized linear and nonlinear dose-response meta-analysis models and used DerSimonian-Laird random-effects meta-analysis models of risk ratios, with inverse variance weighting, and the I2 statistic to quantify heterogeneity. Seventy-four studies including 3 340 684 participants with 242 240 deaths among 2 564 029 participants who reported death events were reviewed. Findings were broadly similar across both linear and nonlinear dose-response models in 30 studies with >1 000 000 participants, and we report results from the linear model. Self-reported duration of sleep >8 hours was associated with a moderate increased risk of all-cause mortality, with risk ratio , 1.14 (1.05-1.25) for 9 hours, risk ratio, 1.30 (1.19-1.42) for 10 hours, and risk ratio, 1.47 (1.33-1.64) for 11 hours. No significant difference was identified for periods of self-reported sleep <7 hours, whereas similar patterns were observed for stroke and cardiovascular disease mortality. Subjective poor sleep quality was associated with coronary heart disease (risk ratio , 1.44; 95% confidence interval, 1.09-1.90), but no difference in mortality and other outcomes. Conclusions Divergence from the recommended 7 to 8 hours of sleep is associated with a higher risk of mortality and cardiovascular events. Longer duration of sleep may be more associated with adverse outcomes compared with shorter sleep durations.
KEYWORDS:
cardiac risk factors; coronary artery disease; meta‐analysis; prevention

Air pollution: Half a million early deaths in Europe despite progress
https://www.bbc.com/news/world-europe-46017339

New study associates highly effective blood pressure medication with small risk of cancer
Findings highlight importance of doctors putting risks versus benefits into perspective for patients
Nicole Ireland · CBC News · Posted: Oct 30, 2018
https://www.cbc.ca/news/health/blood-pressure-medication-ace-inhibitors-cancer-risk-1.4882562
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Angiotensin converting enzyme inhibitors and risk of lung cancer: population based cohort study
BMJ 2018; 363 doi: https://doi.org/10.1136/bmj.k4209 (Published 24 October 2018)
Blánaid M Hicks, postdoctoral research fellow1 2 3, Kristian B Filion, assistant professor of epidemiology1 2 4, Hui Yin, statistician1, Lama Sakr, pulmonologist5, Jacob A Udell, cardiologist and assistant professor of cardiology6 7, Laurent Azoulay, associate professor of epidemiology and oncology1 2 8
Abstract
Objective To determine whether the use of angiotensin converting enzyme inhibitors (ACEIs), compared with use of angiotensin receptor blockers, is associated with an increased risk of lung cancer.
Design Population based cohort study.
Setting United Kingdom Clinical Practice Research Datalink.
Participants A cohort of 992 061 patients newly treated with antihypertensive drugs between 1 January 1995 and 31 December 2015 was identified and followed until 31 December 2016.
Main outcome measures Cox proportional hazards models were used to estimate adjusted hazard ratios with 95% confidence intervals of incident lung cancer associated with the time varying use of ACEIs, compared with use of angiotensin receptor blockers, overall, by cumulative duration of use, and by time since initiation.
Results The cohort was followed for a mean of 6.4 (SD 4.7) years, generating 7952 incident lung cancer events (crude incidence 1.3 (95% confidence interval 1.2 to 1.3) per 1000 person years). Overall, use of ACEIs was associated with an increased risk of lung cancer (incidence rate 1.6 v 1.2 per 1000 person years; hazard ratio 1.14, 95% confidence interval 1.01 to 1.29), compared with use of angiotensin receptor blockers. Hazard ratios gradually increased with longer durations of use, with an association evident after five years of use (hazard ratio 1.22, 1.06 to 1.40) and peaking after more than 10 years of use (1.31, 1.08 to 1.59). Similar findings were observed with time since initiation.
Conclusions In this population based cohort study, the use of ACEIs was associated with an increased risk of lung cancer. The association was particularly elevated among people using ACEIs for more than five years. Additional studies, with long term follow-up, are needed to investigate the effects of these drugs on incidence of lung cancer.

Dietary fiber intake and mortality in a Mediterranean population: the "Seguimiento Universidad de Navarra" (SUN) project.
Dominguez LJ, Bes-Rastrollo M, Toledo E, Gea A, Fresán U, Barbagallo M, Martínez-González MA.
Eur J Nutr. 2018 Oct 26. doi: 10.1007/s00394-018-1846-3. [Epub ahead of print]
PMID: 30367237
Abstract
PURPOSE:
To prospectively assess the association of dietary fiber intake (from different dietary sources) with all-cause mortality in a Mediterranean cohort.
METHODS:
We assessed 19,703 participants of the SUN (Seguimiento Universidad de Navarra) cohort (mean follow-up: 10.1 years). A validated 136-item FFQ was administered at baseline. We used Cox proportional hazards models adjusted for multiple socio-demographic, anthropometric, lifestyle factors, and prevalent conditions at baseline.
RESULTS:
We observed 323 deaths during 198,341 person-years of follow-up. A significantly inverse linear trend in Cox models was observed for the association of total dietary fiber intake and all-cause mortality after adjustment for confounders (p for trend 0.017). Each additional intake of 5 g/1000 kcal of dietary fiber was associated with a 9% relative reduction in all-cause mortality risk (HR 0.91, 95% CI 0.84-0.99). Considering separate dietary sources in separate models, a significant inverse trend was apparent for fiber derived from vegetables (p for trend 0.001), but it was non-significant for fiber derived from fruit, legumes, cereals, or other sources. Soluble fiber was significantly inversely associated with all-cause mortality in the fully adjusted model (p for trend 0.007), and insoluble fiber was marginally significant (p for trend 0.08).
CONCLUSIONS:
A higher intake of total dietary fiber, and particularly fiber from vegetables, was related to a reduced all-cause mortality in our Mediterranean cohort. Dietary messages to increase the consumption of dietary patterns rich in fiber-rich foods should be broadly disseminated to decrease the alarming rate of chronic diseases and its derived mortality.
KEYWORDS:
Cohort; Diet; Fiber; Mortality; Prospective; Vegetables

Preventing colorectal cancer or early diagnosis: Which is best? A re-analysis of the U.S. Preventive Services Task Force Evidence Report.
Swartz AW, Eberth JM, Strayer SM.
Prev Med. 2018 Oct 24. pii: S0091-7435(18)30333-5. doi: 10.1016/j.ypmed.2018.10.014. [Epub ahead of print]
PMID: 30367971
Abstract
Flexible sigmoidoscopy (FS) is the only cancer screening test to lower the risk of death compared to usual care in randomized controlled trials (RCTs). We hypothesize that this unique death reduction is more attributable to prevention of colorectal cancer (CRC) than to early diagnosis. The systematic review of the 2016 US Preventive Services Task Force Evidence Report for CRC Screening was used for selection of RCT studies. A random-effects meta-analysis of five FS trials (N = 458,002) and four fecal occult blood test (FOBT) trials (N = 328,767) was performed using intention-to-screen outcomes for death, CRC incidence, and death attributed to CRC; correlation and linear regression analyses explored the relationships between these outcomes. At 10.5-11.9 years of follow-up FS reduces death (relative risk [RR], 0.975; 95% CI, 0.958-0.992 and reduces CRC incidence (RR, 0.79; 95% CI, 0.74-0.84). Within the FS trials death reduction shows a strong linear correlation with CRC incidence reduction (r, 0.95; 95% CI 0.42-0.99). At 15.6-30.0 years of follow-up FOBT does not reduce death (RR, 1.001; 95% CI, 0.992-1.010) or CRC incidence (RR, 0.96; 95% CI, 0.89-1.02) but does reduce deaths attributed to CRC (RR, 0.84; 95% CI, 0.78-0.91). Clinical trials of screening FS display a dose-response relationship between the magnitude of CRC prevention and the magnitude of death reduction. Prevention of CRC appears to be the major (or sole) mechanism of action for death reduction by FS in clinical trials. Conversely, early diagnosis of CRC does not appear to reduce death.
KEYWORDS:
All-cause mortality; Colorectal cancer; Fecal occult blood test; Flexible sigmoidoscopy; Meta-analysis; Mortality; Overall mortality; Screening

Methionine restriction leads to hyperhomocysteinemia and alters hepatic H2S production capacity in Fischer-344 rats.
Tamanna N, Mayengbam S, House JD, Treberg JR.
Mech Ageing Dev. 2018 Oct 24. pii: S0047-6374(18)30122-2. doi: 10.1016/j.mad.2018.10.004. [Epub ahead of print]
PMID: 30367932
http://sci-hub.tw/http://www.sciencedirect.com/science/article/pii/S0047637418301222
Abstract
Dietary methionine restriction (MR) increases lifespan in several animal models. Despite low dietary intake of sulphur amino acids, rodents on MR develop hyperhomocysteinemia. On the contrary, MR has been reported to increase H2S production in mice. Enzymes involved in homocysteine metabolism also take part in H2S production and hence, in this study, the impact of MR on hyperhomocysteinemia and H2S production capacity were investigated using Fischer-344 rats assigned either a control or a MR diet for 8 weeks. The MR animals showed elevated plasma homocysteine accompanied with a reduction in liver cysteine content and methylation potential. It was further found that MR decreased cystathionine-β-synthase (CBS) activity in the liver, however, MR increased hepatic cystathionine-γ-lyase (CGL) activity which is the second enzyme in the transsulfuration pathway and also participates in regulating H2S production. The relative contribution of CGL in H2S production increased concomitantly with the increased CGL activity. Additionally, hepatic mercaptopyruvate-sulphur-transferase (MPST) activity also increased in response to MR. Taken together, our results suggest that reduced CBS activity and S-Adenosylmethionine availability contributes to hyperhomocysteinimia in MR animals. Elevated CGL and MPST activities may provide a compensatory mechanism for maintaining hepatic H2S production capacity in response to the decreased CBS activity.
KEYWORDS:
H(2)S; longevity; methionine restriction; methylation potential; sulfur amino acids; transsulfuration

Physical activity, fitness, and all-cause mortality: An 18-year follow-up among old people.
Äijö M, Kauppinen M, Kujala UM, Parkatti T.
J Sport Health Sci. 2016 Dec;5(4):437-442. doi: 10.1016/j.jshs.2015.09.008. Epub 2015 Sep 25.
PMID: 30356537
https://www.sciencedirect.com/science/article/pii/S2095254615000952?via%3Dihub
https://ac.els-cdn.com/S2095254615000952/1-s2.0-S2095254615000952-main.pdf?_tid=61fce41c-845b-4542-92a3-c167163f61e3&acdnat=1540657225_cd4ac863ad08b628a756a8a0548783d5
Abstract
BACKGROUND:
Little is known about change in physical activity (PA) and its relationship to all-cause mortality among old people. There is even less information about the association between PA, fitness, and all-cause mortality among people aged 80 years and above. The objective is to investigate persistence and change in PA over 5 years as a predictor of all-cause mortality, and fitness as a mediator of this association, among people aged 80 and 85 years at the beginning of an 18-year mortality follow-up period.
METHODS:
Using Evergreen Project data (started in 1989), 4 study groups were formed according to self-reported changes in PA level, over a 5-year period (starting in 1989-1990 and ending in 1994-1995): remained active (RA, control group), changed to inactive (CI), remained inactive (RI), and changed to active (CA). Mortality was followed up over the 18-year period (1994-2012). Cox models with different covariates such as age, sex, use of alcohol, smoking, chronic diseases, and a 10 m walking test were used to analyze the association between change in PA level and mortality.
RESULTS:
Compared to RA, those who decreased their PA level (CI) between baseline and follow-up had higher all-cause mortality (hazard ratio (HR = 2.09; 95%CI: 1.63-2.69) when adjusted for age, gender, and chronic diseases. RI showed the highest all-cause mortality (HR = 2.16; 95%CI: 1.59-2.93). In CA, when compared against RA, the risk of all-cause mortality was not statistically significant (HR = 1.51; 95%CI: 0.95-2.38). In comparison with RA, when walking speed over 10 m was added as a covariate, all-cause mortality risk was almost statistically significant only in CI (HR = 1.37; 95%CI: 1.00-1.87).
CONCLUSION:
Persistence and change in PA level was associated with mortality. This association was largely explained by fitness status. Randomized controlled studies are needed to test whether maintaining or increasing PA level could lengthen the life of old people.
KEYWORDS:
All-cause mortality; Fitness; Follow-up study; Functional ability; Old people; Physical activity

Can mesenchymal stem cell lysate reverse aging?
Hsu MF, Yu SH, Chuang SJ, Kuo TK, Singal PK, Huang CY, Kao CL, Kuo CH.
Aging (Albany NY). 2018 Oct 24. doi: 10.18632/aging.101595. [Epub ahead of print]
PMID: 30362957
https://www.aging-us.com/article/101595/text
Abstract
Recent findings regarding uses of adipose-derived mesenchymal stem cell (MSC)-lysate on weight loss and improved glucose tolerance in mice on a high-fat diet suggest an encouraging possibility of using MSC lysate for an anti-aging intervention in humans. However, weight loss and lipopenia during late life can be as life-threatening as hyperglycemia during early adulthood. For this 3-year lifelong experiment, a total of 92 rats were randomized into the vehicle-injected group (F=22; M=24) and the MSC lysate injected group (F=22, M=24). We examined longevity, spontaneous locomotor activity, and body composition in rats maintained on a normal diet and received an intermittent treatment of human adipose-derived MSC lysate (3 times a week, 11 times a month given every second month), starting at 12 months of age until natural death. In substantiating previous knowledge regarding the effects of long-term MSC lysate treatments on fat loss and insulin resistance, the present findings also highlighted a shortened average lifespan, a longer inactive time, and a greater bone loss with a relative increase of lean mass in MSC lysate rats with respect to controls. Conclusion: Our data suggest that MSC lysate treatments stimulate disparity in tissue development and produce a cachexia-like effect to decrease longevity.
KEYWORDS:
bone loss; glucose; lifespan; lipopenia; longevity; osteopenia; paracrine effect

Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306 473 UK Biobank participants.
Rutten-Jacobs LC, Larsson SC, Malik R, Rannikmäe K; MEGASTROKE consortium; International Stroke Genetics Consortium, Sudlow CL, Dichgans M, Markus HS, Traylor M.
BMJ. 2018 Oct 24;363:k4168. doi: 10.1136/bmj.k4168.
PMID: 30355576
Abstract
OBJECTIVE:
To evaluate the associations of a polygenic risk score and healthy lifestyle with incident stroke.
DESIGN:
Prospective population based cohort study.
SETTING:
UK Biobank Study, UK.
PARTICIPANTS:
306 473 men and women, aged 40-73 years, recruited between 2006 and 2010.
MAIN OUTCOME MEASURE:
Hazard ratios for a first stroke, estimated using Cox regression. A polygenic risk score of 90 single nucleotide polymorphisms previously associated with stroke was constructed at P<1×10-5 to test for an association with incident stroke. Adherence to a healthy lifestyle was determined on the basis of four factors: non-smoker, healthy diet, body mass index <30 kg/m2, and regular physical exercise.
RESULTS:
During a median follow-up of 7.1 years (2 138 443 person years), 2077 incident strokes (1541 ischaemic stroke, 287 intracerebral haemorrhage, and 249 subarachnoid haemorrhage) were ascertained. The risk of incident stroke was 35% higher among those at high genetic risk (top third of polygenic score) compared with those at low genetic risk (bottom third): hazard ratio 1.35 (95% confidence interval 1.21 to 1.50), P=3.9×10-8. Unfavourable lifestyle (0 or 1 healthy lifestyle factors) was associated with a 66% increased risk of stroke compared with a favourable lifestyle (3 or 4 healthy lifestyle factors): 1.66 (1.45 to 1.89), P=1.19×10-13. The association with lifestyle was independent of genetic risk stratums.
CONCLUSION:
In this cohort study, genetic and lifestyle factors were independently associated with incident stroke. These results emphasise the benefit of entire populations adhering to a healthy lifestyle, independent of genetic risk.

Maternal dietary pattern characterised by high protein and low carbohydrate intake in pregnancy is associated with a higher risk of gestational diabetes mellitus in Chinese women: a prospective cohort study.
Zhou X, Chen R, Zhong C, Wu J, Li X, Li Q, Cui W, Yi N, Xiao M, Yin H, Xiong G, Han W, Hao L, Yang X, Yang N.
Br J Nutr. 2018 Nov;120(9):1045-1055. doi: 10.1017/S0007114518002453.
PMID: 30355392
Abstract
Maternal dietary patterns and macronutrients intake have been shown to affect the development of gestational diabetes mellitus (GDM), but the findings are inconsistent. We aimed to identify maternal dietary patterns and examine their associations with GDM risk, and to evaluate the contributions of macronutrients intake to these associations. We included 2755 Chinese pregnant women from the Tongji Maternal and Child Health Cohort. Dietary intakes were assessed using a validated semi-quantitative FFQ 2 weeks before the diagnosis of GDM. GDM (n 248) was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test at 24-28 weeks gestation. We derived five different dietary patterns from a principal component analysis. The results showed that high fish-meat-eggs scores, which were positively related to protein intake and inversely related to carbohydrate intake, were associated with a higher risk of GDM (adjusted OR for quartile 4 v. quartile 1: 1·83; 95 % CI 1·21, 2·79; P trend=0·007) and higher plasma glucose levels. In contrast, high rice-wheat-fruits scores, which were positively related to carbohydrate intake and inversely related to protein intake, were associated with lower risk of GDM (adjusted OR for quartile 3 v. quartile 1: 0·54; 95 % CI 0·36, 0·83; P trend=0·010) and lower plasma glucose levels. In addition, dietary protein and carbohydrate intake significantly contributed to the associations between dietary patterns and GDM risk or glucose levels. These findings suggest that a dietary pattern characterised by high protein and low carbohydrate intake in pregnancy was associated with a higher risk of GDM, which may provide important clues for dietary guidance during pregnancy to prevent GDM.
KEYWORDS:
GDM gestational diabetes mellitus; NHSII Nurses’ Health Study II; OGTT oral glucose tolerance test; TMCHC Tongji Maternal and Child Health Cohort; Dietary patterns; Gestational diabetes mellitus; Macronutrients; Plasma glucose

Long-term effects of coffee and caffeine intake on the risk of pre-diabetes and type 2 diabetes: Findings from a population with low coffee consumption.
Mirmiran P, Carlström M, Bahadoran Z, Azizi F.
Nutr Metab Cardiovasc Dis. 2018 Sep 12. pii: S0939-4753(18)30271-0. doi: 10.1016/j.numecd.2018.09.001. [Epub ahead of print]
PMID: 30352712
Abstract
BACKGROUND AND AIM:
Here, we examined the potential effect of coffee consumption and total caffeine intake on the occurrence of pre-diabetes and T2D, in a population with low coffee consumption.
METHODS AND RESULTS:
Adults men and women, aged 20-70 years, were followed for a median of 5.8 y. Dietary intakes of coffee and caffeine were estimated using a 168-food items validate semi-quantitative food frequency questionnaire, at baseline. Cox proportional hazards regression models, adjusted for potential cofounders, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between coffee and caffeine intakes and incidence of pre-diabetes and T2D. The total population was 1878 adults (844 men, 1034 women) and 2139 adults (971 men, 1168 women) for analysis of pre-diabetes and T2D, respectively. During the follow-up period the incidence of pre-diabetes and T2D was 30.8% and 6.6%, respectively. Forty-three percent of our subjects were no coffee drinker whereas 51.4% consumed 1 cup of coffee/week and 6.0% consumed more than 1 cup of coffee/week. A lower risk of pre-diabetes (HR = 0.73, 95% CI = 0.62-0.86) and T2D (HR = 0.66, 95% CI = 0.44-1.00) was observed in coffee drinkers compared to non-drinkers, in the fully adjusted models. Higher dietary intake of caffeine (≥152 vs. <65 mg/d) was accompanied with a borderline (P = 0.053) reduced risk of pre-diabetes (HR = 0.45, 95% CI = 0.19-1.00).
CONCLUSION:
Our findings indicated that coffee drinking may have favorable effect in prevention of pre-diabetes and T2D.
KEYWORDS:
Caffeine; Coffee; Pre-diabetes; Type 2 diabetes

Increased longevity in older users of postmenopausal estrogen therapy: the Leisure World Cohort Study.
Paganini-Hill A, Corrada MM, Kawas CH.
Menopause. 2018 Nov;25(11):1256-1261. doi: 10.1097/GME.0000000000001227.
PMID: 30358721
Abstract
OBJECTIVE:
To examine the effect of postmenopausal estrogen therapy (ET), including duration and recency of use, on all-cause mortality in older women.
DESIGN:
As part of a prospective cohort study of residents of a California retirement community begun in the early 1980s, Leisure World Cohort women (median age, 73 y) completed a postal health survey including details on ET use and were followed up for 22 years (1981-2003). Age- and multivariate-adjusted risk ratios (RR) and 95% CIs were calculated using proportional hazard regression.
RESULTS:
Of the 8,801 women, 6,626 died during follow-up (median age, 88 y). ET users had an age-adjusted mortality rate of 52.9 per 1,000 person-years compared with 56.5 among lifetime nonusers (RR = 0.91; 95% CI, 0.87-0.96). Risk of death decreased with both increasing duration of ET and decreasing years since last use (P for trend < 0.001). The risk was lowest among long-term (≥15 y) users (RR = 0.83; 95% CI, 0.74-0.93 for 15-19 y and RR = 0.87; 95% CI, 0.80-0.94 for 201 y). For long-term users, the age-adjusted mortality rate was 50.4 per 1,000 person-years. Lower-dose users (≤0.625 mg) had a slightly better survival rate than higher-dose users (RR = 0.84; 95% CI, 0.78-0.91 vs RR = 0.91; 95% CI, 0.83-0.97). Risk did not differ by route of administration (P = 0.56). Further adjustment for potential confounders had little effect on the observed RRs for ET.
CONCLUSION:
Long-term ET is associated with lower all-cause mortality in older women.

Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians.
Xiao FH, Chen XQ, Yu Q, Ye Y, Liu YW, Yan D, Yang LQ, Chen G, Lin R, Yang L, Liao X, Zhang W, Zhang W, Tang NL, Wang XF, Zhou J, Cai WW, He YH, Kong QP.
Genome Res. 2018 Oct 23. doi: 10.1101/gr.220780.117. [Epub ahead of print]
PMID: 30352807
Abstract
Centenarians (CENs) are excellent subjects to study the mechanisms of human longevity and healthy aging. Here, we analyzed the transcriptomes of 76 centenarians, 54 centenarian-children, and 41 spouses of centenarian-children by RNA sequencing and found that, among the significantly differentially expressed genes (SDEGs) exhibited by CENs, the autophagy-lysosomal pathway is significantly up-regulated. Overexpression of several genes from this pathway, CTSB, ATP6V0C, ATG4D, and WIPI1, could promote autophagy and delay senescence in cultured IMR-90 cells, while overexpression of the Drosophila homolog of WIPI1, Atg18a, extended the life span in transgenic flies. Interestingly, the enhanced autophagy-lysosomal activity could be partially passed on to their offspring, as manifested by their higher levels of both autophagy-encoding genes and serum beclin 1 (BECN1). In light of the normal age-related decline of autophagy-lysosomal functions, these findings provide a compelling explanation for achieving longevity in, at least, female CENs, given the gender bias in our collected samples, and suggest that the enhanced waste-cleaning activity via autophagy may serve as a conserved mechanism to prolong the lifespan from Drosophila to humans.

3D Network exploration and visualisation for lifespan data.
Hühne R, Kessler V, Fürstberger A, Kühlwein S, Platzer M, Sühnel J, Lausser L, Kestler HA.
BMC Bioinformatics. 2018 Oct 23;19(1):390. doi: 10.1186/s12859-018-2393-x.
PMID: 30352578
https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-018-2393-x
Abstract
BACKGROUND:
The Ageing Factor Database AgeFactDB contains a large number of lifespan observations for ageing-related factors like genes, chemical compounds, and other factors such as dietary restriction in different organisms. These data provide quantitative information on the effect of ageing factors from genetic interventions or manipulations of lifespan. Analysis strategies beyond common static database queries are highly desirable for the inspection of complex relationships between AgeFactDB data sets. 3D visualisation can be extremely valuable for advanced data exploration.
RESULTS:
Different types of networks and visualisation strategies are proposed, ranging from basic networks of individual ageing factors for a single species to complex multi-species networks. The augmentation of lifespan observation networks by annotation nodes, like gene ontology terms, is shown to facilitate and speed up data analysis. We developed a new Javascript 3D network viewer JANet that provides the proposed visualisation strategies and has a customised interface for AgeFactDB data. It enables the analysis of gene lists in combination with AgeFactDB data and the interactive visualisation of the results.
CONCLUSION:
Interactive 3D network visualisation allows to supplement complex database queries by a visually guided exploration process. The JANet interface allows gaining deeper insights into lifespan data patterns not accessible by common database queries alone. These concepts can be utilised in many other research fields.
KEYWORDS:
3D visualization; AgeFactDB; Ageing; Ageing factor database; Differentially expressed genes; Gene network; Lifespan

De novo NAD+ synthesis enhances mitochondrial function and improves health.
Katsyuba E, Mottis A, Zietak M, De Franco F, van der Velpen V, Gariani K, Ryu D, Cialabrini L, Matilainen O, Liscio P, Giacchè N, Stokar-Regenscheit N, Legouis D, de Seigneux S, Ivanisevic J, Raffaelli N, Schoonjans K, Pellicciari R, Auwerx J.
Nature. 2018 Oct 24. doi: 10.1038/s41586-018-0645-6. [Epub ahead of print]
PMID: 30356218
https://sci-hub.tw/10.1038/s41586-018-0645-6
Abstract
Nicotinamide adenine dinucleotide (NAD+) is a co-substrate for several enzymes, including the sirtuin family of NAD+-dependent protein deacylases. Beneficial effects of increased NAD+ levels and sirtuin activation on mitochondrial homeostasis, organismal metabolism and lifespan have been established across species. Here we show that α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), the enzyme that limits spontaneous cyclization of α-amino-β-carboxymuconate-ε-semialdehyde in the de novo NAD+ synthesis pathway, controls cellular NAD+ levels via an evolutionarily conserved mechanism in Caenorhabditis elegans and mouse. Genetic and pharmacological inhibition of ACMSD boosts de novo NAD+ synthesis and sirtuin 1 activity, ultimately enhancing mitochondrial function. We also characterize two potent and selective inhibitors of ACMSD. Because expression of ACMSD is largely restricted to kidney and liver, these inhibitors may have therapeutic potential for protection of these tissues from injury. In summary, we identify ACMSD as a key modulator of cellular NAD+ levels, sirtuin activity and mitochondrial homeostasis in kidney and liver.

Can Eating Organic Food Lower Your Cancer Risk?
https://www.nytimes.com/2018/10/23/well/eat/can-eating-organic-food-lower-your-cancer-risk.html
In a study, those who ate more organic produce, dairy, meat and other products had 25 percent fewer cancer diagnoses over all, especially lymphoma and breast cancer.
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Editorial
Organic Foods for Cancer Prevention—Worth the Investment?
Elena C. Hemler, BS; Jorge E. Chavarro, MD, ScD; Frank B. Hu
JAMA Intern Med. Published online October 22, 2018. doi:10.1001/jamainternmed.2018.4363
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2707943
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Association of Organic Food Consumption With Cancer Risk
Association of Frequency of Organic Food Consumption With Cancer Risk -- Findings From the NutriNet-Santé Prospective Cohort Study
Julia Baudry, PhD1; Karen E. Assmann, PhD1; Mathilde Touvier, PhD1; et al Benjamin Allès, PhD1; Louise Seconda, MSc1; Paule Latino-Martel, PhD1; Khaled Ezzedine, MD, PhD1,2; Pilar Galan, MD, PhD1; Serge Hercberg, MD, PhD1,3; Denis Lairon, PhD4; Emmanuelle Kesse-Guyot, PhD1
JAMA Intern Med. Published online October 22, 2018. doi:10.1001/jamainternmed.2018.4357
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2707948
Key Points
Question  What is the association between an organic food–based diet (ie, a diet less likely to contain pesticide residues) and cancer risk?
Findings  In a population-based cohort study of 68 946 French adults, a significant reduction in the risk of cancer was observed among high consumers of organic food.
Meaning  A higher frequency of organic food consumption was associated with a reduced risk of cancer; if the findings are confirmed, promoting organic food consumption in the general population could be a promising preventive strategy against cancer.
Abstract
Importance  Although organic foods are less likely to contain pesticide residues than conventional foods, few studies have examined the association of organic food consumption with cancer risk.
Objective  To prospectively investigate the association between organic food consumption and the risk of cancer in a large cohort of French adults.
Design, Setting, and Participants  In this population-based prospective cohort study among French adult volunteers, data were included from participants with available information on organic food consumption frequency and dietary intake. For 16 products, participants reported their consumption frequency of labeled organic foods (never, occasionally, or most of the time). An organic food score was then computed (range, 0-32 points). The follow-up dates were May 10, 2009, to November 30, 2016.
Main Outcomes and Measures  This study estimated the risk of cancer in association with the organic food score (modeled as quartiles) using Cox proportional hazards regression models adjusted for potential cancer risk factors.
Results  Among 68 946 participants (78.0% female; mean [SD] age at baseline, 44.2 [14.5] years), 1340 first incident cancer cases were identified during follow-up, with the most prevalent being 459 breast cancers, 180 prostate cancers, 135 skin cancers, 99 colorectal cancers, 47 non-Hodgkin lymphomas, and 15 other lymphomas. High organic food scores were inversely associated with the overall risk of cancer (hazard ratio for quartile 4 vs quartile 1, 0.75; 95% CI, 0.63-0.88; P for trend = .001; absolute risk reduction, 0.6%; hazard ratio for a 5-point increase, 0.92; 95% CI, 0.88-0.96).
Conclusions and Relevance  A higher frequency of organic food consumption was associated with a reduced risk of cancer. Although the study findings need to be confirmed, promoting organic food consumption in the general population could be a promising preventive strategy against cancer.

Size matters: height, cell number and a person's risk of cancer
Leonard Nunney
Proc Biol Sci. Published 24 October 2018.DOI: 10.1098/rspb.2018.1743
http://rspb.royalsocietypublishing.org/content/285/1889/20181743
Abstract
The multistage model of carcinogenesis predicts cancer risk will increase with tissue size, since more cells provide more targets for oncogenic somatic mutation. However, this increase is not seen among mammal species of different sizes (Peto's paradox), a paradox argued to be due to larger species evolving added cancer suppression. If this explanation is correct, the cell number effect is still expected within species. Consistent with this, the hazard ratio for overall cancer risk per 10 cm increase in human height (HR10) is about 1.1, indicating a 10% increase in cancer risk per 10 cm; however, an alternative explanation invokes an indirect effect of height, with factors that increase cancer risk independently increasing adult height. The data from four large-scale surveillance projects on 23 cancer categories were tested against quantitative predictions of the cell-number hypothesis, predictions that were accurately supported. For overall cancer risk the HR10 predicted versus observed was 1.13 versus 1.12 for women and 1.11 versus 1.09 for men, suggesting that cell number variation provides a null hypothesis for assessing height effects. Melanoma showed an unexpectedly strong relationship to height, indicating an additional effect, perhaps due to an increasing cell division rate mediated through increasing IGF-I with height. Similarly, only about one-third of the higher incidence of non-reproductive cancers in men versus women can be explained by cell number. The cancer risks of obesity are not correlated with effects of height, consistent with different primary causation. The direct effect of height on cancer risk suggests caution in identifying height-related SNPs as cancer causing.

Dietary sugars, exercise and hepatic carbohydrate metabolism.
Gonzalez JT, Betts JA.
Proc Nutr Soc. 2018 Oct 23:1-11. doi: 10.1017/S0029665118002604. [Epub ahead of print]
PMID: 30348238
Abstract
The present paper reviews the physiological responses of human liver carbohydrate metabolism to physical activity and ingestion of dietary sugars. The liver represents a central link in human carbohydrate metabolism and a mechanistic crux point for the effects of dietary sugars on athletic performance and metabolic health. As a corollary, knowledge regarding physiological responses to sugar ingestion has potential application to either improve endurance performance in athletes, or target metabolic diseases in people who are overweight, obese and/or sedentary. For example, exercise increases whole-body glycogen utilisation, and the breakdown of liver glycogen to maintain blood glucose concentrations becomes increasingly important as exercise intensity increases. Accordingly, prolonged exercise at moderate-to-high exercise intensity results in depletion of liver glycogen stores unless carbohydrate is ingested during exercise. The exercise-induced glycogen deficit can increase insulin sensitivity and blood glucose control, and may result in less hepatic lipid synthesis. Therefore, the induction and maintenance of a glycogen deficit with exercise could be a specific target to improve metabolic health and could be achieved by carbohydrate (sugar) restriction before, during and/or after exercise. Conversely, for athletes, maintaining and restoring these glycogen stores is a priority when competing in events requiring repeated exertion with limited recovery. With this in mind, evidence consistently demonstrates that fructose-containing sugars accelerate post-exercise liver glycogen repletion and could reduce recovery time by as much as half that seen with ingestion of glucose (polymers)-only. Therefore, athletes aiming for rapid recovery in multi-stage events should consider ingesting fructose-containing sugars to accelerate recovery.
KEYWORDS:
P phosphate; UDP uridine diphosphate; Fructose; Galactose; Glucose; Glycogen; Physical activity

A multi-tissue full lifespan epigenetic clock for mice.
Thompson MJ, Chwiałkowska K, Rubbi L, Lusis AJ, Davis RC, Srivastava A, Korstanje R, Churchill GA, Horvath S, Pellegrini M.
Aging (Albany NY). 2018 Oct 21. doi: 10.18632/aging.101590. [Epub ahead of print]
PMID: 30348905
Abstract
Human DNA-methylation data have been used to develop highly accurate biomarkers of aging ("epigenetic clocks"). Recent studies demonstrate that similar epigenetic clocks for mice (Mus Musculus) can be slowed by gold standard anti-aging interventions such as calorie restriction and growth hormone receptor knock-outs. Using DNA methylation data from previous publications with data collected in house for a total 1189 samples spanning 193,651 CpG sites, we developed 4 novel epigenetic clocks by choosing different regression models (elastic net- versus ridge regression) and by considering different sets of CpGs (all CpGs vs highly conserved CpGs). We demonstrate that accurate age estimators can be built on the basis of highly conserved CpGs. However, the most accurate clock results from applying elastic net regression to all CpGs. While the anti-aging effect of calorie restriction could be detected with all types of epigenetic clocks, only ridge regression based clocks replicated the finding of slow epigenetic aging effects in dwarf mice. Overall, this study demonstrates that there are trade-offs when it comes to epigenetic clocks in mice. Highly accurate clocks might not be optimal for detecting the beneficial effects of anti-aging interventions.
KEYWORDS:
DNA methylation; biological age; epigenetic clock; mouse

Dose-response association of dietary sodium intake with all-cause and cardiovascular mortality: a systematic review and meta-analysis of prospective studies.
Milajerdi A, Djafarian K, Shab-Bidar S.
Public Health Nutr. 2018 Oct 22:1-12. doi: 10.1017/S1368980018002112. [Epub ahead of print]
PMID: 30345950
Abstract
OBJECTIVE:
High Na intake has been associated with different health problems. However, serious controversies exist over studies investigating associations of Na intake with mortality from all-causes and CVD. The present systematic review and meta-analysis was done to investigate, for the first time, the dose-response association of dietary Na intake with all-cause and CVD mortality among prospective studies.
DESIGN:
Relevant papers published up to August 2017 were searched in MEDLINE, EMBASE and Google Scholar databases. Prospective cohort studies on the association of dietary Na intake with all-cause or/and CVD mortality were included. Linear and non-linear dose-response associations between Na intake and CVD and all-cause mortality were examined.
RESULTS:
Overall, twenty publications met inclusion criteria. A significant non-linear association (P<0·001) was found between Na intake and CVD mortality risk among studies assessing urinary Na excretion, with a relatively steep slope at Na intakes above 2400mg/d. However, the association was not significant in studies using dietary Na intake (P=0·61). Additionally, the non-linear association of Na intake with all-cause mortality was also non-significant. No linear association (effect size; 95 % CI; I2) was seen between 100mg/d increment in Na intake and CVD mortality (1·01; 0·97, 1·05; 98·4 %) or all-cause mortality (1·01; 1·00, 1·02; 89·2 %). Following subgroup analyses, the association between Na intake and CVD mortality was observed only among studies conducted in the USA (0·99; 0·99, 1·00; 20·0 %).
CONCLUSIONS:
The study showed a direct association between urinary Na excretion and CVD mortality which was more considerable at intakes above 2400mg/d. In contrast, no significant association was found between Na intake and all-cause mortality. Further long-term prospective studies on different populations are required to confirm these findings.
KEYWORDS:
All-cause mortality; Cardiovascular mortality; Meta-analysis; Sodium; Systematic review

Effect of monosodium L-glutamate (umami substance) on cognitive function in people with dementia.
Kouzuki M, Taniguchi M, Suzuki T, Nagano M, Nakamura S, Katsumata Y, Matsumoto H, Urakami K.
Eur J Clin Nutr. 2018 Oct 22. doi: 10.1038/s41430-018-0349-x. [Epub ahead of print]
PMID: 30349139
http://sci-hub.tw/http://www.nature.com/articles/s41430-018-0349-x
Abstract
BACKGROUND/OBJECTIVES:
This study assessed the effect of continuous ingestion of monosodium L-glutamate (MSG) on cognitive function and dietary score in dementia patients.
SUBJECTS/METHODS:
This was a single-blind, placebo-controlled trial involving 159 subjects with dementia residing in a hospital or nursing home. We assigned the subjects to a group that ingested MSG thrice daily (0.9 g/dose) (MSG group; n = 79) or a group that ingested NaCl thrice daily (0.26 g/dose) (Control group; n = 80). This study consisted of a 12-week intake period, followed by a 4-week follow-up period without the ingestion of MSG or NaCl. We performed physical examination, cognitive symptom tests (the Touch Panel-type Dementia Assessment Scale (TDAS) and Gottfries-Bråne-Steen Scale (GBSS)), palatability and behaviour questionnaires, and blood tests before and after the intervention and after the follow-up period.
RESULTS:
There were no significant differences in the TDAS and GBSS total scores between the groups before and after the intervention. However, regarding the TDAS sub-items, "the accuracy of the order of a process" did not deteriorate in the MSG group compared with that observed in the Control group (p < 0.05). At the follow-up assessment, the TDAS total scores in the MSG group showed significant improvement compared with those reported in the Control group (p < 0.05). Furthermore, there was a correlation of changes from pre-intervention to post-intervention between the TDAS and enjoyment of the meal (r = -0.299, p = 0.049).
CONCLUSIONS:
Our results suggest that continued ingestion of MSG has an effect on cognitive function. Furthermore, the patients with improved questionnaires about palatability survey showed greater improvement in cognitive function.

Aspirin intake in the morning is associated with suboptimal platelet inhibition, as measured by serum Thromboxane B2, during infarct-prone early-morning hours.
Racca C, van Diemen JJK, Fuijkschot WW, Spit K, Bonten TN, Numans ME, van der Bom JG, Smulders YM, Thijs A.
Platelets. 2018 Oct 22:1-7. doi: 10.1080/09537104.2018.1528347. [Epub ahead of print]
PMID: 30346860
Abstract
Aspirin is traditionally taken once daily in the morning and considered to be effective throughout the 24h interval. Cardiovascular events occur most frequently in the early morning, suggesting that these hours are critical in terms of adequate platelet inhibition. This study therefore assed platelet function in the early morning-8.00 AM-in healthy volunteers, during a once-daily (OD) 80 mg morning in comparison with an OD evening regimen and a twice-daily (BID) 40 mg regimen. It was an open-label randomized cross-over study, comprising 12 healthy subjects. Subjects were allocated to three sequential dosage regimens: 80 mg OD at 8.00 AM, 80mg OD at 8.00 PM, and 40 mg BID at 8.00 AM and PM. Platelet function 12 and 24 hours after aspirin intake was measured by means of serum thromboxane B2 (sTxB2) levels, the collagen/epinephrine closure time (Platelet Function Analyzer(PFA)-200®) and the Aspirin Reaction Units (ARU, VerifyNow®). The results demonstrated that early morning sTxB2 concentrations were 5843pg in the morning regimen, 2877pg in the evening OD regimen, and 3343pg in the BID regimen (morning- vs evening regimen p = < 0.01; morning- vs BID regimen p = < 0.01). Early morning PFA-closure time (p = 0.12)) as well as VerifyNow ARU (p = 0.17) mean values were similar for all three regimens. In conclusion, the OD-morning regimen seems to acquire the lowest level of platelet inhibition during the critical early morning window. Switching to an OD-evening or BID intake seems prudent, although further research on clinical cardiovascular outcome in patients with stable cardiovascular disease is needed.
KEYWORDS:
Cross-over trial; aspirin; chronotherapy; circadian rhythm; platelet aggregation

Polyunsaturated Fatty Acids and Their Potential Therapeutic Role in Cardiovascular System Disorders-A Review.
Sokoła-Wysoczańska E, Wysoczański T, Wagner J, Czyż K, Bodkowski R, Lochyński S, Patkowska-Sokoła B.
Nutrients. 2018 Oct 21;10(10). pii: E1561. doi: 10.3390/nu10101561. Review.
PMID: 30347877
https://www.mdpi.com/2072-6643/10/10/1561/htm
Abstract
Cardiovascular diseases are described as the leading cause of morbidity and mortality in modern societies. Therefore, the importance of cardiovascular diseases prevention is widely reflected in the increasing number of reports on the topic among the key scientific research efforts of the recent period. The importance of essential fatty acids (EFAs) has been recognized in the fields of cardiac science and cardiac medicine, with the significant effects of various fatty acids having been confirmed by experimental studies. Polyunsaturated fatty acids are considered to be important versatile mediators for improving and maintaining human health over the entire lifespan, however, only the cardiac effect has been extensively documented. Recently, it has been shown that omega-3 fatty acids may play a beneficial role in several human pathologies, such as obesity and diabetes mellitus type 2, and are also associated with a reduced incidence of stroke and atherosclerosis, and decreased incidence of cardiovascular diseases. A reasonable diet and wise supplementation of omega-3 EFAs are essential in the prevention and treatment of cardiovascular diseases prevention and treatment.
KEYWORDS:
alpha-linoleic acid (ALA); cardiovascular system; docosahexaenoic acid (DHA); eicosapentaenoic acid (EPA); lipids; nutrition; omega-3 fatty acids

Life expectancy in Canada may be decreasing for first time in decades, and opioid crisis is being blamed
https://www.cbc.ca/news/health/life-expectancy-canada-decrease-opioid-crisis-1.4874651
On average, Canadians have been steadily living longer over many years, but a new report says that 'alarmingly,' it's expected to change.

Neurocognitive and Hormonal Correlates of Voluntary Weight Loss in Humans.
Neseliler S, Hu W, Larcher K, Zacchia M, Dadar M, Scala SG, Lamarche M, Zeighami Y, Stotland SC, Larocque M, Marliss EB, Dagher A.
Cell Metab. 2018 Oct 15. pii: S1550-4131(18)30632-6. doi: 10.1016/j.cmet.2018.09.024. [Epub ahead of print]
PMID: 30344017
https://sci-hub.tw/10.1016/j.cmet.2018.09.024
Abstract
Insufficient responses to hypocaloric diets have been attributed to hormonal adaptations that override self-control of food intake. We tested this hypothesis by measuring circulating energy-balance hormones and brain functional magnetic resonance imaging reactivity to food cues in 24 overweight/obese participants before, and 1 and 3 months after starting a calorie restriction diet. Increased activity and functional connectivity in prefrontal regions at month 1 correlated with weight loss at months 1 and 3. Weight loss was also correlated with increased plasma ghrelin and decreased leptin, and these changes were associated with food cue reactivity in reward-related brain regions. However, the reduction in leptin did not counteract weight loss; indeed, it was correlated with further weight loss at month 3. Activation in prefrontal regions associated with self-control could contribute to successful weight loss and maintenance. This work supports the role of higher-level cognitive brain function in body-weight regulation in humans.
KEYWORDS:
DLPFC; VMPFC; appetite; fMRI; ghrelin; leptin; obesity; self-control

Impact of adherence to cancer-specific prevention recommendations on subsequent risk of cancer in participants in Alberta's Tomorrow Project.
Xu JY, Vena JE, Whelan HK, Robson PJ.
Public Health Nutr. 2018 Oct 22:1-11. doi: 10.1017/S1368980018002689. [Epub ahead of print]
PMID: 30345944
https://sci-hub.tw/https://www.cambridge.org/core/journals/public-health-nutrition/article/impact-of-adherence-to-cancerspecific-prevention-recommendations-on-subsequent-risk-of-cancer-in-participants-in-albertas-tomorrow-project/9CB5FCF4BAC094E06882E393031A292A
Abstract
Aspirin is one of the most often used drugs for prevention and treatment of a variety of thrombotic disorders. This narrative review aims to provide an overview of evidence highlighting potential benefits and relative harms of aspirin in primary prevention of cardiovascular disease. The authors summarize key findings of the ASPirin in Reducing Events in the Elderly (ASPREE) Investigator Group randomized trial and also provide a comparative overview of recent meta-analyses. Overall, all-cause mortality was largely heterogeneous, with some meta-analyses showing a modestly decreased risk in patients taking aspirin, with others reporting no effects, but the ASPREE Investigator Group trial evidencing 14% higher risk. Regarding cardiovascular disease, the most favorable impact could be noted for major adverse cardiovascular events, with most meta-analyses reporting a decreased risk in people receiving aspirin. Conversely, the ASPREE Investigator Group trial demonstrated no significant impact of aspirin on risk of cardiovascular mortality or ischemic stroke. A modest favorable effect of aspirin in decreasing the risk of myocardial infarction was noted in two meta-analyses, but not in other reports or in the ASPREE Investigator Group trial. Furthermore, one meta-analysis reported a lower risk of future cancer, others failed to report a significant effect, and the ASPREE Investigator Group trial reported a 31% increased risk. Unlike these conflicting outcomes, the bleeding risk of patients receiving aspirin was found to be consistently enhanced in all reports reviewed. These recent findings would lead us to conclude that the harms of aspirin in primary prevention of cardiovascular disease may be larger than the benefits, especially in the elderly general population.

Harms and Benefits of Using Aspirin for Primary Prevention of Cardiovascular Disease: A Narrative Overview.
Lippi G, Danese E, Favaloro EJ.
Semin Thromb Hemost. 2018 Oct 22. doi: 10.1055/s-0038-1675380. [Epub ahead of print]
PMID: 30347414
Abstract
Aspirin is one of the most often used drugs for prevention and treatment of a variety of thrombotic disorders. This narrative review aims to provide an overview of evidence highlighting potential benefits and relative harms of aspirin in primary prevention of cardiovascular disease. The authors summarize key findings of the ASPirin in Reducing Events in the Elderly (ASPREE) Investigator Group randomized trial and also provide a comparative overview of recent meta-analyses. Overall, all-cause mortality was largely heterogeneous, with some meta-analyses showing a modestly decreased risk in patients taking aspirin, with others reporting no effects, but the ASPREE Investigator Group trial evidencing 14% higher risk. Regarding cardiovascular disease, the most favorable impact could be noted for major adverse cardiovascular events, with most meta-analyses reporting a decreased risk in people receiving aspirin. Conversely, the ASPREE Investigator Group trial demonstrated no significant impact of aspirin on risk of cardiovascular mortality or ischemic stroke. A modest favorable effect of aspirin in decreasing the risk of myocardial infarction was noted in two meta-analyses, but not in other reports or in the ASPREE Investigator Group trial. Furthermore, one meta-analysis reported a lower risk of future cancer, others failed to report a significant effect, and the ASPREE Investigator Group trial reported a 31% increased risk. Unlike these conflicting outcomes, the bleeding risk of patients receiving aspirin was found to be consistently enhanced in all reports reviewed. These recent findings would lead us to conclude that the harms of aspirin in primary prevention of cardiovascular disease may be larger than the benefits, especially in the elderly general population.
Relationships between Vegetarian Dietary Habits and Daily Well-Being.
Nezlek JB, Forestell CA, Newman DB.
Ecol Food Nutr. 2018 Oct 22:1-14. doi: 10.1080/03670244.2018.1536657. [Epub ahead of print]
PMID: 30346834
https://sci-hub.tw/10.1080/03670244.2018.1536657
Abstract
The goal of the present study was to examine differences in the daily experiences of vegetarians and non-vegetarians. At the end of each day for two weeks, a convenience sample of American undergraduates described how they felt and how they thought about themselves that day, and they described the events that occurred to them that day. Multilevel modeling analyses (days nested within persons) found that vegetarians (individuals who avoided all meat and fish, n = 24) reported lower self-esteem, lower psychological adjustment, less meaning in life, and more negative moods than semi-vegetarians (individuals who ate some meat and/or fish, n = 56) and omnivores (individuals who did not restrict their intake of meat or fish, n = 323). Vegetarians also reported more negative social experiences than omnivores and semi-vegetarians. Although women were more likely than men to identify as vegetarians and semi-vegetarians, controlling for participant gender did not change the results of the analyses. The differences we found are consistent with other research that suggests that vegetarians are less psychologically well-adjusted than non-vegetarians. The implications of the present results for understanding relationships between dietary habits and well-being are discussed.
KEYWORDS:
Daily diary; vegetarianism; well-being

Associations Between Changes in Cycling and All-Cause Mortality Risk.
Østergaard L, Jensen MK, Overvad K, Tjønneland A, Grøntved A.
Am J Prev Med. 2018 Nov;55(5):615-623. doi: 10.1016/j.amepre.2018.06.009.
PMID: 30342627
Abstract
INTRODUCTION:
Previous cohort studies have reported relationships of active commuting, walking, and cycling with mortality. No studies have separately examined commuter and recreational cycling and how changes in cycling are related to mortality.
METHODS:
Prospective cohort study among individuals who were between 50 and 65years and living in Denmark at the baseline examination between 1993 and 1997. Commuter/recreational cycling and changes in cycling were investigated in analytic samples of 28,204 and 15,272 participants, respectively. Participants were asked to provide information on cycling habits and other risk factors for mortality at baseline and 5years later and were followed for risk of death until July 2013. Data were analyzed in 2018.
RESULTS:
Cycling between 1 and 60 minutes per week was associated with lower risk of all-cause mortality, with an appertaining multivariable adjusted hazard ratio of 0.76 (95% CI=0.69, 0.83) for recreational cycling and 0.78 (95% CI=0.63, 0.96) for commuter cycling when compared with no cycling. Compared with those who never cycled, the hazard ratio for those who initiated cycling was 0.78 (95% CI=0.67, 0.90) and the hazard ratio for those who consistently cycled was 0.77 (95% CI=0.71, 0.84), whereas the hazard ratio for those who stopped cycling was 0.98 (95% CI=0.87, 1.11).
CONCLUSIONS:
Initiation of, or continued engagement in, cycling late in mid-life is associated with a lower risk of all-cause mortality. It may be suggested that national and local governments prioritize resources to promote cycling.

Association of Dietary Nitrate Intake with the 15-Year Incidence of Age-Related Macular Degeneration.
Gopinath B, Liew G, Kifley A, Lewis JR, Bondonno C, Joachim N, Hodgson JM, Mitchell P.
J Acad Nutr Diet. 2018 Oct 17. pii: S2212-2672(18)30276-4. doi: 10.1016/j.jand.2018.07.012. [Epub ahead of print]
PMID: 30342988
https://sci-hub.tw/10.1016/j.jand.2018.07.012
Abstract
BACKGROUND:
Dietary nitrate, found predominantly in green leafy vegetables and beetroot, is a precursor of nitric oxide. Under- or overproduction of nitric oxide is implicated in the etiology of several eye diseases. However, the potential influence of dietary nitrate intake on age-related macular degeneration (AMD) risk has not been assessed.
OBJECTIVE:
To investigate the temporal association between dietary nitrate intake (from both vegetable and nonvegetable sources) and the 15-year incidence of AMD, independent of potential confounders.
DESIGN:
A longitudinal cohort study conducted from 1992-1994 to 2007-2009.
PARTICIPANTS/SETTING:
The Blue Mountains Eye Study is a population-based study of adults aged 49+ at baseline, from a region west of Sydney, Australia. At baseline, 2,856 participants with complete dietary data and AMD information were examined, and of these, 2,037 participants were re-examined 15 years later and thus included in incidence analysis.
MAIN OUTCOMES MEASURED:
Incidence of AMD (main outcome) was assessed from retinal photographs. Dietary intake was assessed using a semiquantitative food-frequency questionnaire. Nitrate intake from vegetables and nonvegetable sources was calculated by use of a validated comprehensive database.
RESULTS:
After adjusting for age, sex, smoking, energy intake, fish consumption, and AMD risk alleles (complement factor H and age-related maculopathy susceptibility-2 single nucleotide polymorphisms), participants in the third quartile compared with those in the first quartile (reference group) of total nitrate and total vegetable nitrate intake had reduced risk of incident early AMD: odds ratio (OR) 0.61 (95% CI 0.41 to 0.90) and OR 0.65 (95% CI 0.44 to 0.96), respectively. Significant associations were not observed between the fourth vs first quartile of total nitrate and vegetable nitrate intake with incident early AMD: OR 0.74 (95% CI 0.51 to 1.08) and OR 0.69 (95% CI 0.47 to 1.00), respectively. Nonsignificant associations were also observed with 15-year incidence of late AMD and total nonvegetable nitrate intake.
CONCLUSIONS:
These novel findings could have important implications, if the association between total nitrate intake and vegetable nitrate intake and 15-year incidence of early AMD is confirmed in other observational or intervention studies.
KEYWORDS:
Age-related macular degeneration; Blue Mountains Eye Study; Nitrates; Vegetables

Prevalence of Chronic Liver Disease Among the Patients of Celiac Disease and Effect of Gluten-Free Diet on Outcome of Liver Disease: A Prospective Study.
Mule A, Sirohi P, Ram N.
J Assoc Physicians India. 2018 Mar;66(3):34-36.
PMID: 30341866
http://www.japi.org/march_2018/8_oa_Prevalence_of_Chronic.pdf
Abstract
OBJECTIVE:
Descriptive reports of liver involvement in celiac disease (CD) are sparse, and the effect of a strict gluten-free diet (GFD) on the course of liver injury is also poorly understood. We conducted a study on 94 adult patients with CD and found that 39 of them were having chronic liver disease as well. We further followed patients of 'CD with CLD' with strict Gluten-free diet (GFD) for six months.
METHODS:
We screened 94 patients of CD for CLD and found 39 patients to have CLD as well. We further followed these 39 patients of 'CD with CLD' for six month with strict gluten-free diet. Follow up was done in terms of Child Pugh score. We recorded their clinical as well as laboratory findings after 1 month, 3 months and 6 months and compared them with those at the time of recruitment.
RESULTS:
The liver involvement was found in 39(41.5%) out of 94 patients celiac disease. Mean Child-Pugh score on admission was 10.22±1.09 and on first follow-up mean Child-Pugh score was 7.38±1.47 was found to be statistically highly significant (p <0.001) Mean Child-Pugh score on admission was 10.15±1.09 and on second follow-up 7.33±1.33 respectively and was statistically highly significant (p <0.001) Mean Child-Pugh score on admission was 10.12±1.09 and on third follow-up mean Child-Pugh score was 6.31±0.93 respectively was statistically highly significant (p <0.001).

Coffee consumption and liver-related hospitalizations and deaths in the ARIC study.
Hu EA, Lazo M, Selvin E, Hamilton JP, Grams ME, Steffen LM, Coresh J, Rebholz CM.
Eur J Clin Nutr. 2018 Oct 19. doi: 10.1038/s41430-018-0346-0. [Epub ahead of print]
PMID: 30341433
http://sci-hub.tw/http://www.nature.com/articles/s41430-018-0346-0
Abstract
BACKGROUND/OBJECTIVES:
Coffee consumption has been found to be associated with reduced risk of chronic conditions such as liver disease. However, less is known about the association between coffee and liver-related hospitalizations and deaths.
SUBJECTS/METHODS:
We conducted a prospective analysis on 14,208 participants aged 45-64 years from the Atherosclerosis Risk in Communities (ARIC) study. Coffee consumption (cups/day) was assessed using food frequency questionnaires at visit 1 (1987-89) and visit 3 (1993-95). Liver-related hospitalizations were defined as a hospitalization with any International Classification of Diseases, Ninth Revision (ICD-9) code related to liver disease identified through cohort surveillance. Liver-related death was defined as any death with a liver disease ICD-9 code listed anywhere on the death certificate form.
RESULTS:
There were 833 incident cases of liver-related hospitalizations over a median follow-up of 24 years and 152 liver-related deaths over a median follow-up of 25 years. Participants who were in the highest category of coffee consumption (≥ 3 cups/day) were more likely to be men, whites, current smokers, and current alcohol drinkers. In our fully adjusted model, consuming ≥ 3 cups/day of coffee was significantly associated with a reduced risk of liver-related hospitalizations compared with never drinkers (hazard ratio: 0.79, 95% CI: 0.63-0.99). There were no significant associations between coffee consumption and liver-related deaths after adjusting for covariates.
CONCLUSIONS:
Coffee drinkers may be at lower risk for liver-related hospitalizations. This supports current evidence that low and moderate levels of coffee may be protective to the liver.

Association of sodium intake and major cardiovascular outcomes: a dose-response meta-analysis of prospective cohort studies.
Zhu Y, Zhang J, Li Z, Liu Y, Fan X, Zhang Y, Zhang Y.
BMC Cardiovasc Disord. 2018 Oct 19;18(1):192. doi: 10.1186/s12872-018-0927-9.
PMID: 30340541
https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-018-0927-9
https://bmccardiovascdisord.biomedcentral.com/track/pdf/10.1186/s12872-018-0927-9
Abstract
BACKGROUND:
The association of sodium intake with the risk of cardiovascular morbidity and mortality is inconsistent. Thus, the present meta-analysis was conducted to summarize the strength of association between sodium intake and cardiovascular morbidity and mortality.
METHODS:
PubMed, Embase, and the Cochrane Library were searched systematically to identify the relevant studies up to October 2017. The effect estimates for 100 mmol/day increase in sodium intake were calculated using 95% confidence intervals (CIs) of cardiac death, total mortality, stroke, or stroke mortality for low (< 3 g/d), moderate (3-5 g/d), or heavy (> 5 g/d) sodium intake, and minimal sodium intake comparison.
RESULTS:
A total of 16 prospective cohort studies reported data on 205,575 individuals. The results suggested that an increase in sodium intake by 100 mmol/d demonstrated little or no effect on the risk of cardiac death (P = 0.718) and total mortality (P = 0.720). However, the risk of stroke incidence (P = 0.029) and stroke mortality (P = 0.007) was increased significantly by 100 mmol/day increment of sodium intake. Furthermore, low sodium intake was associated with an increased risk of cardiac death (P = 0.003), while moderate (P < 0.001) or heavy (P = 0.001) sodium intake was associated with an increased risk of stroke mortality.
CONCLUSIONS:
These findings suggested that sodium intake by 100 mmol/d increment was associated with an increased risk of stroke incidence and stroke mortality. Furthermore, low sodium intake was related to an increased cardiac death risk, while moderate or heavy sodium intake was related to an increased risk of stroke mortality.
KEYWORDS:
Cardiovascular outcomes; Dose-response; Meta-analysis; Prospective cohort studies; Sodium intake

Associations of maternal caffeine intake with birth outcomes: results from the Lifeways Cross Generation Cohort Study.
Chen LW, Fitzgerald R, Murrin CM, Mehegan J, Kelleher CC, Phillips CM; Lifeways Cross Generation Cohort Study.
Am J Clin Nutr. 2018 Oct 19. doi: 10.1093/ajcn/nqy219. [Epub ahead of print]
PMID: 30339199
Abstract
BACKGROUND:
Maternal caffeine intake is associated with adverse birth outcomes, but in most studies the primary caffeine source is coffee; the influence of tea caffeine remains unclear.
OBJECTIVE:
The aim of the study was to examine the association between maternal caffeine intake and birth outcomes in a population with tea as the predominant caffeine source.
DESIGN:
Data from 941 Irish mother-child pairs of the Lifeways Cross Generation Cohort Study were examined. Maternal dietary intakes in early pregnancy were assessed using a validated food-frequency questionnaire. Caffeine intake was derived from coffee, tea, soft drinks, and cocoa-containing foods and beverages. Associations of maternal caffeine intake with continuous (birth weight, birth length, and gestational age) and binary [low birth weight (LBW) (<2500 g) and preterm birth (PB) (<37 wk gestational age)] birth outcomes were investigated using multiple linear and logistic regressions, respectively, with adjustment for potential confounders.
RESULTS:
Tea was the predominant caffeine source (48%), followed by coffee (39%). In the fully adjusted model, maternal caffeine intake was associated with lower birth weight [β (95% CI): -71.9 (-105.4, -38.4) g · 100 mg-1 · d-1 caffeine increment], shorter birth length [-0.30 (-0.49, -0.11) cm], smaller head circumference [-0.12 (-0.24, -0.01) cm], and shorter gestational age [-0.13 (-0.25, -0.02) wk]; higher risks for LBW [OR (95% CI): 1.47 (1.14, 1.90)] and PB [1.36 (1.07, 1.74)] were also observed (all P < 0.05). The associations were robust to the exclusion of participants with pregnancy complications and in never smokers. Similar higher risks of adverse birth outcomes were observed for the highest caffeine intake categories from coffee [ORLBW: 3.10 (1.08, 8.89); ORPB: 2.74 (1.05, 7.16)] and tea [ORLBW: 2.47 (1.02, 6.01); ORPB: 2.56 (1.14, 5.75)], compared with the lowest intake categories (all P < 0.05).
CONCLUSIONS:
Maternal caffeine intake from both coffee and tea is associated with adverse birth outcomes. 

The effects of caffeine intake on weight loss: a systematic review and dos-response meta-analysis of randomized controlled trials.
Tabrizi R, Saneei P, Lankarani KB, Akbari M, Kolahdooz F, Esmaillzadeh A, Nadi-Ravandi S, Mazoochi M, Asemi Z.
Crit Rev Food Sci Nutr. 2018 Oct 18:1-9. doi: 10.1080/10408398.2018.1507996. [Epub ahead of print]
PMID: 30335479
Abstract
This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to summarize the effect of caffeine intake on weight loss. We searched the following databases until November 2017: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The relevant data were extracted and assessed for quality of the studies according to the Cochrane risk of bias tool. We estimated an intake-status regression coefficient (Beta) for each primary study and estimated the overall pooled Beta and SE using random effects meta-analysis on a double-log scale. Heterogeneity between studies was assessed by the Cochran Q statistic and I-squared tests (I2). Thirteen RCTs with 606 participants were included in the meta-analyses. The overall pooled Beta for the effect of caffeine intake was 0.29 (95%CI: 0.19, 0.40; Q  =  124.5, I2 = 91.2%) for weigh, 0.23 (95%CI: 0.09, 0.36; Q  =  71.0, I2 = 93.0%) for BMI, and 0.36 (95% CI: 0.24, 0.48; Q  =  167.36, I2 = 94.0%) for fat mass. For every doubling in caffeine intake, the mean reduction in weight, BMI, and fat mass increased 2 Beta-fold (20.29  =  1.22, 20.23  =  1.17, and 20.36  =  1.28), which corresponding to 22, 17, and 28 percent, respectively. Overall, the current meta-analysis demonstrated that caffeine intake might promote weight, BMI and body fat reduction.
KEYWORDS:
Caffeine; meta-analysis; weight loss

Serial circulating omega 3 polyunsaturated fatty acids and healthy ageing among older adults in the Cardiovascular Health Study: prospective cohort study.
Lai HT, de Oliveira Otto MC, Lemaitre RN, McKnight B, Song X, King IB, Chaves PH, Odden MC, Newman AB, Siscovick DS, Mozaffarian D.
BMJ. 2018 Oct 17;363:k4067. doi: 10.1136/bmj.k4067.
PMID: 30333104 Free Article
https://www.bmj.com/content/363/bmj.k4067.long
https://www.bmj.com/content/bmj/363/bmj.k4067.full.pdf
Abstract
OBJECTIVE:
To determine the longitudinal association between serial biomarker measures of circulating omega 3 polyunsaturated fatty acid (n3-PUFA) levels and healthy ageing.
DESIGN:
Prospective cohort study.
SETTING:
Four communities in the United States (Cardiovascular Health Study) from 1992 to 2015.
PARTICIPANTS:
2622 adults with a mean (SD) age of 74.4 (4.8) and with successful healthy ageing at baseline in 1992-93.
EXPOSURE:
Cumulative levels of plasma phospholipid n3-PUFAs were measured using gas chromatography in 1992-93, 1998-99, and 2005-06, expressed as percentage of total fatty acids, including α-linolenic acid from plants and eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid from seafoood.
MAIN OUTCOME MEASURE:
Healthy ageing defined as survival without chronic diseases (ie, cardiovascular disease, cancer, lung disease, and severe chronic kidney disease), the absence of cognitive and physical dysfunction, or death from other causes not part of the healthy ageing outcome after age 65. Events were centrally adjudicated or determined from medical records and diagnostic tests.
RESULTS:
Higher levels of long chain n3-PUFAs were associated with an 18% lower risk (95% confidence interval 7% to 28%) of unhealthy ageing per interquintile range after multivariable adjustments with time-varying exposure and covariates. Individually, higher eicosapentaenoic acid and docosapentaenoic acid (but not docosahexaenoic acid) levels were associated with a lower risk: 15% (6% to 23%) and 16% (6% to 25%), respectively. α-linolenic acid from plants was not noticeably associated with unhealthy ageing (hazard ratio 0.92, 95% confidence interval 0.83 to 1.02).
CONCLUSIONS:
In older adults, a higher cumulative level of serially measured circulating n3-PUFAs from seafood (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid), eicosapentaenoic acid, and docosapentaenoic acid (but not docosahexaenoic acid from seafood or α-linolenic acid from plants) was associated with a higher likelihood of healthy ageing. These findings support guidelines for increased dietary consumption of n3-PUFAs in older adults.

Observational Evidence for Unintentional Weight Loss in All-Cause Mortality and Major Cardiovascular Events: A Systematic Review and Meta-Analysis.
De Stefani FDC, Pietraroia PS, Fernandes-Silva MM, Faria-Neto J, Baena CP.
Sci Rep. 2018 Oct 18;8(1):15447. doi: 10.1038/s41598-018-33563-z.
PMID: 30337578
Abstract
The obesity paradox has been described in several observational cohorts and meta-analysis. However, evidence of the intentionality of weight loss in all-cause deaths and major cardiovascular events (MACE) in prospective cohorts is unclear. We analysed whether involuntary weight loss is associated with increased cardiovascular events and mortality. In a systematic review, we searched multiple electronic databases for observational studies published up to October 2016. Studies reporting risk estimates for unintentional weight loss compared with stable weight in MACE and mortality were included. Fifteen studies met the selection criteria, with a total of 178,644 participants. For unintentional weight loss, we found adjusted risk ratios (RRs) with confidence intervals (CIs) of 1.38 (95% CI: 1.23, 1.53) and 1.17 (95% CI: 0.98, 1.37) for all-cause mortality and MACE, respectively. Participants with comorbidities, overweight and obese populations, and older adults yielded RRs (95% CI) of 1.49 (1.30, 1.68), 1.11 (1.04, 1.18), and 1.81 (1.59, 2.03), respectively. Unintentional weight loss had a significant impact on all-cause mortality. We found no protective effect of being overweight or obese for unintentional weight loss and MACE.

Increased environmental temperature normalizes energy metabolism outputs between normal and Ames dwarf mice.
Darcy J, McFadden S, Fang Y, Berryman DE, List EO, Milcik N, Bartke A.
Aging (Albany NY). 2018 Oct 18. doi: 10.18632/aging.101582. [Epub ahead of print]
PMID: 30334813
https://www.aging-us.com/article/101582/text
https://s3-us-west-1.amazonaws.com/paperchase-aging/pdf/uyiQguXL8Pz8yQRe4.pdf
Abstract
Ames dwarf (Prop1df) mice possess a loss-of-function mutation that results in deficiency of growth hormone, prolactin, and thyroid-stimulating hormone, as well as exceptional longevity. Work in other laboratories suggests that increased respiration and lipid utilization are important for maximizing mammalian longevity. Interestingly, these phenotypes are observed in Ames dwarf mice. We recently demonstrated that Ames dwarf mice have hyperactive brown adipose tissue (BAT), and hypothesized that this may in part be due to their increased surface to mass ratio leading to increased heat loss and an increased demand for thermogenesis. Here, we used increased environmental temperature (eT) to interrogate this hypothesis. We found that increased eT diminished BAT activity in Ames dwarf mice, and led to the normalization of both VO2 and respiratory quotient between dwarf and normal mice, as well as partial normalization (i.e. impairment) of glucose homeostasis in Ames dwarf mice housed at an increased eT. Together, these data suggest that an increased demand for thermogenesis is partially responsible for the improved energy metabolism and glucose homeostasis which are observed in Ames dwarf mice.
KEYWORDS:
Ames dwarf; aging; energy metabolism; thermogenesis

SIRT1 knock-in mice preserve ovarian reserve resembling caloric restriction.
Long GY, Yang JY, Xu JJ, Ni YH, Zhou XL, Ma JY, Fu YC, Luo LL.
Gene. 2018 Oct 16. pii: S0378-1119(18)31074-6. doi: 10.1016/j.gene.2018.10.040. [Epub ahead of print]
PMID: 30340050
Abstract
Previous studies have proposed that caloric restriction (CR) regulates many cell functions and prolongs the lifespan of an organism. Our previous studies proposed that CR also prevents follicular activation and preserves the ovarian reserve in mice by activating SIRT1. To test if SIRT1 preserves the ovarian reserve and prolongs the ovarian longevity, we generated SIRT1 knock-in mice that can overexpress SIRT1 in oocytes of the mouse. Ovaries of the mice at ages 35 days and 15 months were collected, and the follicular development and follicular reserve were examined. The vaginal opening and onset of estrus of transgenic female mice (both the homozygous and heterozygous for SIRT1 overexpression) were later than that of wild-type mice. Both the homozygous and heterozygous SIRT1-overexpressing mice had a larger and stronger reproductive capacity than wild-type mice. Moreover, 35-day-old and 15-month-old homozygous and heterozygous SIRT1-overexpressing mice also had a higher mean number and percentage of healthy follicles, fewer atretic follicles than wild-type mice, and the mean number and percentage of primordial follicles in both the homozygous and heterozygous SIRT1-overexpressing mice were higher than wild-type mice at the same age. However, the phenotypes of heterozygous and homozygous transgenic mice came no difference. Immunohistochemistry showed increased expression of SIRT1 and FOXO3a, and decreased expression of mTOR in both the homozygous and heterozygous SIRT1-overexpressing mice compared with wild-type mice. Thus, oocyte-specific SIRT1-overexpressing mice continuously activate FOXO3a and suppress mTOR and have a larger reproductive capacity, larger follicle reserve and longer ovarian lifespan.
KEYWORDS:
Caloric restriction;FOXO3a; Ovarian reserve; SIRT1 knock-in mice; mTOR

Carbotoxicity-Noxious Effects of Carbohydrates.
Kroemer G, López-Otín C, Madeo F, de Cabo R.
Cell. 2018 Oct 18;175(3):605-614. doi: 10.1016/j.cell.2018.07.044. Review.
PMID: 30340032
https://sci-hub.tw/10.1016/j.cell.2018.07.044
Abstract
Modern nutrition is often characterized by the excessive intake of different types of carbohydrates ranging from digestible polysaccharides to refined sugars that collectively mediate noxious effects on human health, a phenomenon that we refer to as "carbotoxicity." Epidemiological and experimental evidence combined with clinical intervention trials underscore the negative impact of excessive carbohydrate uptake, as well as the beneficial effects of reducing carbs in the diet. We discuss the molecular, cellular, and neuroendocrine mechanisms that link exaggerated carbohydrate intake to disease and accelerated aging as we outline dietary and pharmacologic strategies to combat carbotoxicity.
KEYWORDS:
aging; diabetes; diet; health; longevity; metabolism; nutrition; obesity; restriction; sugar

Effect of Consumption of Cocoa-Derived Products on Uric Acid Crystallization in Urine of Healthy Volunteers.
Costa-Bauza A, Grases F, Calvó P, Rodriguez A, Prieto RM.
Nutrients. 2018 Oct 16;10(10). pii: E1516. doi: 10.3390/nu10101516.
PMID: 30332783
Abstract
The purpose of this study was to determine the effects of consumption of different cocoa-derived products on uric acid crystallization in urine of 20 healthy volunteers. Participants were requested to select the specific diet that they wished to follow during the 12 h prior to collection of urine. The only restriction was that the diet could not include any product with cocoa, coffee, or caffeine. On the first day, each volunteer followed their selected diet, and an overnight 12 h urine sample was collected as the baseline urine. After seven days on an unrestricted diet, each volunteer repeated the same diet with 20 g of milk chocolate, chocolate powder, or dark chocolate during breakfast and another 20 g during dinner. Overnight 12 h urine samples were then collected. Urine volume, pH, oxalate, creatinine, uric acid, theobromine, and a uric acid crystallization test were determined for each sample. The results for all 20 patients show that uric acid crystallization was significantly lower following the consumption of chocolate powder or dark chocolate relative to baseline or following the consumption of milk chocolate. The results indicated that increased concentrations of urinary theobromine reduced the risk of uric acid crystallization.
KEYWORDS:
cocoa; theobromine; therapy; uric acid; urolithiasis

Morning Home Blood Pressure and Cardiovascular Events in a Japanese General Practice Population Over 80 Years Old: The J-HOP Study.
Kawauchi D, Hoshide S, Kario K.
Am J Hypertens. 2018 Oct 15;31(11):1190-1196. doi: 10.1093/ajh/hpy116.
PMID: 30188989
https://www.mdpi.com/2072-6643/10/10/1516/htm
Abstract
BACKGROUND:
Home blood pressure (BP) measurement has been well accepted for use in the diagnosis and treatment of hypertension. However, data regarding the association between home BP levels and cardiovascular events in a general practice population aged ≥80 years are sparse.
METHODS:
We analyzed the cases of 349 patients ≥80 years old from the Japan Morning Surge-Home Blood Pressure (J-HOP) Study, a nationwide practice-based study of 4,310 Japanese with a history of and/or risk factors for cardiovascular disease. Home BP measurements were performed twice daily (morning and evening) over 14 consecutive days at baseline.
RESULTS:
During a median follow-up of 3.0 years, 32 composite cardiovascular events (13 strokes and 19 nonstroke events) occurred. Higher morning systolic BP (SBP) was a significant risk factor for composite cardiovascular events (hazard ratio (HR) per 10mm Hg, 1.23; 95% confidence interval (CI): 1.01-1.50) and stroke events (HR per 10mm Hg, 1.47; 95% CI: 1.08-2.00) after adjustment by the 4-year cardiovascular risk scores and clinic SBP. In the adjusted model, morning diastolic BP also tended to be a significant risk factor of stroke events (HR per 5 mm Hg, 1.43; 95% CI: 1.00-2.05). However, these associations were not found for evening BP or clinic BP.
CONCLUSIONS:
Morning home BP showed a positive linear association with cardiovascular events, especially with stroke. This association was not observed for clinic BP or evening home BP. Based on these results, in very elderly Asian populations, measuring morning home BP might be important in clinical practice regardless of the individual's office BP level.
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Morning and Evening Home Blood Pressure and Risks of Incident Stroke and Coronary Artery Disease in the Japanese General Practice Population: The Japan Morning Surge-Home Blood Pressure Study.
Hoshide S, Yano Y, Haimoto H, Yamagiwa K, Uchiba K, Nagasaka S, Matsui Y, Nakamura A, Fukutomi M, Eguchi K, Ishikawa J, Kario K; J-HOP Study Group.
Hypertension. 2016 Jul;68(1):54-61. doi: 10.1161/HYPERTENSIONAHA.116.07201. Epub 2016 May 9.
PMID: 27160200
http://hyper.ahajournals.org/content/hypertensionaha/68/1/54.full.pdf
Abstract
Our aim is to determine the optimal time schedule for home blood pressure (BP) monitoring that best predicts stroke and coronary artery disease in general practice. The Japan Morning Surge-Home Blood Pressure (J-HOP) study is a nationwide practice-based study that included 4310 Japanese with a history of or risk factors for cardiovascular disease, or both (mean age, 65 years; 79% used antihypertensive medication). Home BP measures were taken twice daily (morning and evening) over 14 days at baseline. During a mean follow-up of 4 years (16 929 person-years), 74 stroke and 77 coronary artery disease events occurred. Morning systolic BP (SBP) improved the discrimination of incident stroke (C statistics, 0.802; 95% confidence interval, 0.692-0.911) beyond traditional risk factors including office SBP (0.756; 0.646-0.866), whereas the changes were smaller with evening SBP (0.764; 0.653-0.874). The addition of evening SBP to the model (including traditional risk factors plus morning SBP) significantly reduced the discrimination of incident stroke (C statistics difference, -0.008; 95% confidence interval: -0.015 to -0.008; P=0.03). The category-free net reclassification improvement (0.3606; 95% confidence interval, 0.1317-0.5896), absolute integrated discrimination improvement (0.015; SE, 0.005), and relative integrated discrimination improvement (58.3%; all P<0.01) with the addition of morning SBP to the model (including traditional risk factors) were greater than those with evening SBP and with combined morning and evening SBP. Neither morning nor evening SBP improved coronary artery disease risk prediction. Morning home SBP itself should be evaluated to ensure best stroke prediction in clinical practice, at least in Japan. This should be confirmed in the different ethnic groups.
CLINICAL TRIAL REGISTRATION:
URL: http://www.umin.ac.jp/ctr/. Unique identifier: UMIN000000894.
KEYWORDS:
Japan; blood pressure monitoring, home ethnic groups; stroke general practice

[AlPater]

Association Between a 20-Year Cardiovascular Disease Risk Score Based on Modifiable Lifestyles and Total and Cause-Specific Mortality Among US Men and Women.
Sotos-Prieto M, Mattei J, Cook NR, Hu FB, Willett WC, Chiuve SE, Rimm EB, Sesso HD.
J Am Heart Assoc. 2018 Nov 6;7(21):e010052. doi: 10.1161/JAHA.118.010052.
Abstract
Background The previously validated Healthy Heart Score effectively predicted the 20-year risk of cardiovascular disease (CVD). We examine whether the Healthy Heart Score may extend to an association with total and cause-specific mortality. Methods and results The prospective cohort study investigated 58 319 women (mean age 50.2 years) in the Nurses' Health Study (1984-2010) and 29 854 in men (mean age 52.7 years) in the Health Professionals' Follow-up Study (1986-2010) free of cancer and CVD at baseline. The Healthy Heart Score included baseline current smoking; high body mass index; low physical activity; no or excessive alcohol intake; low intake of fruits and vegetables, cereal fiber, or nuts; and high intake of sugar-sweetened beverages or red/processed meats. There were 19 122 total deaths. Compared with participants in the first quintile of the Healthy Heart Score (lowest CVD risk), participants in the fifth quintile (highest CVD risk) had a pooled hazard ratio of 2.26 (95% confidence interval [CI], 1.53-3.33) for total mortality; 2.85 (95 % CI, 1.92-4.23) for CVD mortality, and 2.14 (95% CI, 1.56-2.95) for cancer mortality. Participants in the fifth versus the first quintile also had significantly greater risk of death due to coronary heart disease (3.37; 95% CI, 2.16-5.25), stroke (1.75; 95% CI, 1.02-2.99), lung cancer (6.04; 95% CI, 2.78-13.13), breast cancer (1.45; 95% CI, 1.14-1.86), and colon cancer (1.51; 95% CI, 1.18-1.93). Conclusions The Healthy Heart Score, composed of 9 self-reported, modifiable lifestyle predictors of CVD, is a potentially useful tool for the counseling of healthy lifestyles that was strongly associated with greater risk of all-cause, CVD, and cancer mortality.
KEYWORDS:
cohort study; lifestyle; mortality; prevention; risk scorePMID: 30373451
https://www.ahajournals.org/doi/pdf/10.1161/JAHA.118.010052

Body mass index trajectories across adulthood and smoking in relation to prostate cancer risks: the NIH-AARP Diet and Health Study.
Kelly SP, Lennon H, Sperrin M, Matthews C, Freedman ND, Albanes D, Leitzmann MF, Renehan AG, Cook MB.
Int J Epidemiol. 2018 Oct 29. doi: 10.1093/ije/dyy219. [Epub ahead of print]
PMID: 30376043
Abstract
BACKGROUND:
Previously we showed that adulthood body mass index (BMI) trajectories that result in obesity were associated with elevated risks of fatal prostate cancer (PCA). To further explore this relationship, we conducted a study within the NIH-AARP Diet and Health Study.
METHODS:
Among 153 730 eligible men enrolled in the NIH-AARP cohort from 1995 to 1996 (median follow-up = 15.1 years), we identified 630 fatal PCA cases and 16 896 incident cases. BMI was assessed for ages 18, 35 and 50 and at study entry, enabling examination of latent class-identified BMI trajectories. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression.
RESULTS:
BMI at study entry (mean age = 63, HR = 1.12; 95% CI = 1.01, 1.24, per 5-unit increase) and maximum BMI during adulthood (HR = 1.12; 95% CI = 1.02, 1.24, per 5-unit increase) shared modest associations with increased risk of fatal PCA. Smoking status likely modified the relationship between BMI trajectories and fatal PCA (Pinteraction = 0.035 via change-in-estimate variable section, P = 0.065 via full a priori model). Among never-smokers, BMI trajectory of normal weight to obesity was associated with increased risk of fatal disease (HR = 2.37; 95% CI = 1.38, 4.09), compared with the maintained normal weight trajectory, whereas there was no association among former or current-smokers. Total and non-aggressive PCA exhibited modest inverse associations with BMI at all ages, whereas no association was observed for aggressive PCA.
CONCLUSIONS:
Increased BMI was positively associated with fatal PCA, especially among never-smokers. Future studies that examine PCA survival will provide additional insight as to whether these associations are the result of biology or confounding.

Effect of Dietary Flaxseed Intake on Circulating Sex Hormone Levels among Postmenopausal Women: A Randomized Controlled Intervention Trial.
Chang VC, Cotterchio M, Boucher BA, Jenkins DJA, Mirea L, McCann SE, Thompson LU.
Nutr Cancer. 2018 Oct 30:1-14. doi: 10.1080/01635581.2018.1516789. [Epub ahead of print]
PMID: 30375890
Abstract
Lignan intake, and its richest food source, flaxseed, have been associated with reduced breast cancer risk. Endogenous sex hormones, such as estrogens, play a role in breast cancer development, and lignans may alter these sex hormone levels. To assess the effect of flaxseed on circulating sex hormones, a randomized controlled trial was conducted among 99 postmenopausal women in Toronto, Canada. The intervention arm consumed 2 tablespoons (15 g) of ground flaxseed daily for 7 weeks; the control arm maintained usual diet. Baseline and week 7 concentrations of 14 serum sex hormones were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunoassay, and serum enterolignans (lignan biomarker) using LC-MS/MS. Intervention effects on sex hormone levels were assessed using analysis of covariance. Serum enterolignans increased among the flaxseed arm (+516%). Women consuming flaxseed (vs. controls) had increased serum 2-hydroxyestrone [treatment effect ratio (TER) = 1.54; 95% CI: 1.18-2.00] and 2:16α-hydroxyestrone ratio (TER =1.54; 95% CI: 1.15-2.06); effects on other hormones were not statistically significant. Within the flaxseed arm, change in enterolignan level was positively correlated with changes in 2-hydroxyestrone and 2:16α-hydroxyestrone ratio, and negatively with prolactin. Findings suggest flaxseed affects certain circulating sex hormone levels with possible implications for future breast cancer prevention research.

Longitudinal changes in leukocyte telomere length and mortality in elderly Swedish men.
Yuan X, Kronström M, Hellenius ML, Cederholm T, Xu D, Sjögren P.
Aging (Albany NY). 2018 Oct 29. doi: 10.18632/aging.101611. [Epub ahead of print]
PMID: 30375983
https://www.aging-us.com/article/101611/text
Abstract
Telomere length (TL) is considered an indicator of aging and age-related diseases, but longitudinal studies on TL changes and mortality are few. We therefore analyzed TL and longitudinal changes in TL in relation to all-cause, cardiovascular, and cancer mortality in 247 elderly Swedish men. TL was determined by the qPCR method at ages 71 and 81 and subsequent mortality cases were identified from the Swedish cause-of-death registry. Cox proportional hazard ratios were calculated during a mean follow-up of 7.4 years, during which 178 deaths occurred. Short telomeres at baseline was strongly associated with mortality risks, with a 40 to 70% increased risk of all-cause mortality, and a 2-fold increased risk of cancer mortality. Longitudinal changes in TL revealed shortening in 83% of individuals, whilst 10% extended their telomeres. TL attrition did not predict all-cause or cancer mortality, but we found a 60% decreased risk for cardiovascular mortality in those who shortened their telomeres. Our data show an increased risk of mortality in individuals with short baseline telomeres, but no relations to all-cause, and cancer mortality for changes in TL. Intriguingly, our data indicate lower risk of cardiovascular mortality with shortening of telomeres. The latter should be interpreted cautiously.
KEYWORDS:
cause-specific mortality; cohort study; longitudinal changes; mortality; telomere length

[Amti-aging gene]"Klotho deficiency causes thymic involution via systemic effects that include high active vitamin D levels."
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Thymic Epithelial Cell Support of Thymopoiesis Does Not Require Klotho.
Xing Y, Smith MJ, Goetz CA, McElmurry RT, Parker SL, Min D, Hollander GA, Weinberg KI, Tolar J, Stefanski HE, Blazar BR.
J Immunol. 2018 Oct 29. pii: ji1800670. doi: 10.4049/jimmunol.1800670. [Epub ahead of print]
PMID: 30373854
Abstract
Age-related thymic involution is characterized by a decrease in thymic epithelial cell (TEC) number and function parallel to a disruption in their spatial organization, resulting in defective thymocyte development and proliferation as well as peripheral T cell dysfunction. Deficiency of Klotho, an antiaging gene and modifier of fibroblast growth factor signaling, causes premature aging. To investigate the role of Klotho in accelerated age-dependent thymic involution, we conducted a comprehensive analysis of thymopoiesis and peripheral T cell homeostasis using Klotho-deficient (Kl/Kl) mice. At 8 wk of age, Kl/Kl mice displayed a severe reduction in the number of thymocytes (10-100-fold reduction), especially CD4 and CD8 double-positive cells, and a reduction of both cortical and medullary TECs. To address a cell-autonomous role for Klotho in TEC biology, we implanted neonatal thymi from Klotho-deficient and -sufficient mice into athymic hosts. Kl/Kl thymus grafts supported thymopoiesis equivalently to Klotho-sufficient thymus transplants, indicating that Klotho is not intrinsically essential for TEC support of thymopoiesis. Moreover, lethally irradiated hosts given Kl/Kl or wild-type bone marrow had normal thymocyte development and comparably reconstituted T cells, indicating that Klotho is not inherently essential for peripheral T cell reconstitution. Because Kl/Kl mice have higher levels of serum phosphorus, calcium, and vitamin D, we evaluated thymus function in Kl/Kl mice fed with a vitamin D-deprived diet. We observed that a vitamin D-deprived diet abrogated thymic involution and T cell lymphopenia in 8-wk-old Kl/Kl mice. Taken together, our data suggest that Klotho deficiency causes thymic involution via systemic effects that include high active vitamin D levels.

[Baby mice and natto:]
Disgust vs. Delight: Why Do Certain Foods Turn You Off?
“I want people to question what they find disgusting,” said the lead curator and chief financier of the Disgusting Food Museum, a touring pop-up exhibition in Malmo, Sweden.
By Christina Anderson
Oct. 30, 2018
https://www.nytimes.com/2018/10/30/world/europe/sweden-food-museum-disgusting.html

[AlPater]

Wait at least a year before conceiving another baby to minimize health risks, new study suggests
Women who get pregnant 6 months after giving birth more prone to rare but severe complications
Nicole Ireland · CBC News · Posted: Oct 31, 2018 
https://www.cbc.ca/news/health/space-out-pregnancies-by-at-least-a-year-study-1.4884979

Dietary fiber intake and reduced risk of ovarian cancer: a meta-analysis.
Zheng B, Shen H, Han H, Han T, Qin Y.
Nutr J. 2018 Oct 30;17(1):99. doi: 10.1186/s12937-018-0407-1.
PMID: 30376840
https://nutritionj.biomedcentral.com/track/pdf/10.1186/s12937-018-0407-1
Abstract
BACKGROUND:
Epidemiological studies regarding the association between dietary fiber intake and ovarian cancer risk are still inconsistent. We aimed to review the available evidence and conduct a dose-response meta-analysis to investigate the relationship between dietary fiber intake and ovarian cancer risk.
METHODS:
Relevant studies were identified by searching PubMed, EMBASE, and the Cochrane Library databases before August 2017. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between dietary fiber intake and risk of ovarian cancer were included. Random-effects models were used to combine the estimated effects extracted from individual study.
RESULTS:
Thirteen studies, with a total of 5777 ovarian cancer cases and 142,189 participants, met the inclusion criteria. The pooled multivariable RRs of ovarian cancer for the highest vs. the lowest category of dietary fiber intake was 0.78 (95% CI: 0.70, 0.88) with no evidence of heterogeneity (I2 = 4.20%, P = 0.40). Our dose-response analysis also showed a significant inverse association between dietary fiber intake and ovarian cancer risk (an increment of 10 g/day; combined RR: 0.88; 95% CI: 0.82, 0.93). There was no evidence for a nonlinear association (P for nonlinearity = 0.83).
CONCLUSIONS:
This meta-analysis suggests a significant inverse dose-response association between dietary fiber intake and ovarian cancer risk. Further studies with prospective design that take account of more potential confounders are warranted to confirm this association.
KEYWORDS:
Dietary fiber; Meta-analysis; Ovarian cancer; Protective factor

Effect of single caffeine intake on neuropsychological functions in healthy volunteers: A double-blind placebo-controlled study.
Konishi Y, Hori H, Ide K, Katsuki A, Atake K, Igata R, Kubo T, Tominaga H, Beppu H, Asahara T, Yoshimura R.
PLoS One. 2018 Oct 31;13(10):e0202247. doi: 10.1371/journal.pone.0202247. eCollection 2018.
PMID: 30379815
https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0202247&type=printable
Abstract
OBJECTIVE:
We investigated the effects of a single instance of caffeine intake on neurocognitive functions and driving performance in healthy subjects using an established cognitive battery and a driving simulator system.
METHODS:
This study was conducted in a double-blind, randomized, placebo-controlled manner from February 19, 2016 to August 6, 2016. Caffeine intake was discontinued 3 days prior to the study. Participants were randomly assigned to receive 200-mg doses of caffeine or a placebo. Thirty minutes after administration, cognitive functions were evaluated via the Symbol Digit Coding Test (SDC), the Stroop Test (ST), the Shifting Attention Test (SAT) and the Four Part Continuous Performance Test (FPCPT). After the cognitive function tests were conducted, driving performance was evaluated using a driving simulator. We measured the brake reaction time (BRT) in the Harsh-braking test and the standard deviation of the lateral position (SDLP) in the Road-tracking test.
RESULTS:
Of 100 randomized subjects, 50 (50%) of 100 in the caffeine group and 50 (50%) of 100 in the placebo group completed the study. Participants in the caffeine group had more correct responses than participants in the placebo group on the SAT (P = 0.03) and made fewer errors (P = 0.02). Participants in the caffeine group exhibited shorter times in the Harsh-braking test than participants in the placebo group (P = 0.048).
CONCLUSIONS:
A single instance of caffeine intake changed some neurocognitive functions and driving performance in healthy volunteers.

[AlPater]

Higher baseline dietary fat and fatty acid intake is associated with increased risk of incident prostate cancer in the SABOR study.
Liss MA, Al-Bayati O, Gelfond J, Goros M, Ullevig S, DiGiovanni J, Hamilton-Reeves J, O'Keefe D, Bacich D, Weaver B, Leach R, Thompson IM.
Prostate Cancer Prostatic Dis. 2018 Nov 1. doi: 10.1038/s41391-018-0105-2. [Epub ahead of print]
PMID: 30385837
http://sci-hub.tw/http://www.nature.com/articles/s41391-018-0105-2
Abstract
BACKGROUND:
To study the association of nutrient intake measured by baseline food frequency questionnaire and risk of subsequent prostate cancer (PCa) in the SABOR (San Antonio Biomarkers of Risk) cohort study.
METHODS:
After IRB approval, more than 1903 men enrolled in a prospective cohort from 2000 to 2010 as part of the SABOR clinical validation site for the National Cancer Institute Early Detection Research Network. Food and nutrient intakes were calculated using a Food Frequency Questionnaire. Cox proportional hazards modeling and covariate-balanced propensity scores were used to assess the associations between all nutrients and PCa.
RESULTS:
A total of 229 men were diagnosed with PCa by prostate biopsy. Among all nutrients, increased risk of PCa was associated with intake of dietary fat scaled by the total caloric intake, particularly saturated fatty acid (SFA) [HR 1.19; 95% CI, 1.07-1.32), P value < 0.001, False discovery rate (FDR) 0.047] and trans fatty acid (TFA) [HR per quintile 1.21; (95% CI) (1.08-1.35), P < 0.001, FDR 0.039]. There was an increased risk of PCa with increasing intake of monounsaturated fatty acid (MUFA) (HR per quintile 1.14; 95% CI 1.03-1.27, P = 0.01, FDR 0.15) and cholesterol [HR per quintile 1.13; 95% confidence interval (95% CI) (1.02-1.26), P-value 0.02, FDR 0.19].
CONCLUSION:
After examining a large, population-based cohort for PCa diagnosis, we identified dietary total fat and certain fatty acids as associated with increased risk of PCa. We found no factors that were protective from PCa. Dietary modification of fatty acid intake may reduce risk of PCa.

The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial.
Wirth M, Benson G, Schwarz C, Köbe T, Grittner U, Schmitz D, Sigrist SJ, Bohlken J, Stekovic S, Madeo F, Flöel A.
Cortex. 2018 Oct 4;109:181-188. doi: 10.1016/j.cortex.2018.09.014. [Epub ahead of print]
PMID: 30388439
Abstract
INTRODUCTION:
Nutritional intervention with the natural polyamine spermidine, an autophagy-enhancing agent, can prevent memory loss in aging model organisms. This is the first human study to evaluate the impact of spermidine supplementation on memory performance in older adults at risk for the development of Alzheimer's disease.
METHODS:
Cognitively intact participants with subjective cognitive decline (n = 30, 60-80 years of age) were included in this three-months, randomized, placebo-controlled, double-blind Phase IIa pilot trial with a spermidine-rich plant extract supplement. Effects of intervention were assessed using the behavioral mnemonic similarity task, measured at baseline and post-intervention visits. Data analysis was focused on reporting and interpreting effectiveness based on effect sizes.
RESULTS:
Memory performance was moderately enhanced in the spermidine group compared with placebo at the end of intervention [contrast mean = .17, 95% confidence interval (CI): -.01, .35, Cohen's d = .77, 95% CI: 0, 1.53]. Mnemonic discrimination ability improved in the spermidine-treated group with a medium effect size (mean difference = -.11, 95% CI: -.19, -.03, Cohen's d = .79, 95% CI: .01, 1.55). A similar effect was not found in the placebo-treated group (mean difference = .07, 95% CI: -.13, .27, Cohen's d = -.20, 95% CI: -.94, .54).
DISCUSSION:
In this pilot trial, nutritional spermidine was associated with a positive impact on memory performance in older adults with subject cognitive decline. The beneficial effect might be mediated by stimulation of neuromodulatory actions in the memory system. A follow-up Phase IIb randomized controlled trial will help validate the therapeutic potential of spermidine supplementation and delineate possible neurophysiological mechanisms of action.
KEYWORDS:
Cognition; Diet supplementation; Polyamine; Prevention; SmartAge; Subjective cognitive decline

https://en.wikipedia.org/wiki/Adiponectin#Function
Circulating adiponectin levels are paradoxically associated with mortality rate. A systematic review and meta-analysis.
Scarale MG, Fontana A, Trischitta V, Copetti M, Menzaghi C.
J Clin Endocrinol Metab. 2018 Nov 1. doi: 10.1210/jc.2018-01501. [Epub ahead of print]
PMID: 30388239
Abstract
CONTEXT:
Some studies have surprisingly indicated that serum adiponectin is positively related to mortality rate, thus casting doubts on its role as a therapeutic target for cardiovascular disease.
OBJECTIVE:
To summarize evidence about direction, strength and modulators of this controversial association.
DATA SOURCES:
MEDLINE, Web of Science, CINHAL, Cochrane Library and Scopus from inception through June 2018.
STUDY SELECTION:
English-language prospective studies reporting the association between adiponectin and all-cause or cardiovascular mortality.
DATA EXTRACTION:
Two investigators independently extracted data and assessed study quality using standard criteria following the Preferred Reporting Items for Systematic Reviews and Meta-analyses and The Newcastle-Ottawa Scale, respectively. Pooled hazard ratios (HRs) (95% confidence intervals-CIs) were derived using a fixed or random effects models when appropriated and were expressed for one standard deviation (SD) increment of adiponectin.
DATA SYNTHESIS:
We identified fifty-five (n=61,676 subjects) and twenty-eight (n=43,979 subjects) studies for all-cause and cardiovascular mortality, respectively. Pooled HRs, were 1.24 (1.17-1.31) and 1.28 (1.19-1.37) for all-cause and cardiovascular mortality, respectively. Similar results were obtained also for High Molecular Weight adiponectin. When meta-analyses were restricted to studies reporting data on natriuretic peptides a 43% and 28% reduction on a log scale of these associations were observed after natriuretic peptides adjustment.
CONCLUSIONS:
Our results strongly points to a paradoxical association between high adiponectin levels and increased mortality rate, which is partly modulated by natriuretic peptides.

Novel anti-aging gene NM_026333 contributes to proton-induced aging via NCX1-pathway.
Osanai T, Tanaka M, Mikami K, Kitajima M, Tomisawa T, Magota K, Tomita H, Okumura K.
J Mol Cell Cardiol. 2018 Oct 29. pii: S0022-2828(18)30553-4. doi: 10.1016/j.yjmcc.2018.10.021. [Epub ahead of print]
PMID: 30385152
Abstract
Diet-induced metabolic acidosis is associated with the impairment of bone metabolism and an increased risk of a number of chronic noncommunicable diseases, such as type 2 diabetes mellitus and hypertension. Low serum bicarbonate is associated with high mortality in healthy older individuals. Recently, we demonstrated that both coupling factor 6 (CF6)-overexpressing transgenic (TG) and high salt-fed mice which had sustained intracellular acidosis, due to enhanced proton import through ecto-F1Fo complex and/or reduced proton export through Na+-K+ ATPase inhibition, displayed shortened lifespan and early senescence-associated phenotypes such as signs of hair greying and alopecia, weight loss, and/or reduced organ mass. In this study, we searched causative genes of proton-induced aging in CF6-overexpressing TG and high salt-fed mice. We discovered NM_026333 as a novel anti-aging gene which was downregulated in the heart and kidney in both types of mice. NM_026333 protein consists of 269 amino acids with transmembrane region (90-193aa). Induction of NM_026333 or recombinant protein rescued TG cells and CF6-treated human cells from aging hallmarks of impaired autophagy, genomic instability, and epigenetic alteration. NM_026333 protein directly bound plasma membrane Na+-Ca2+ exchanger 1 (NCX1) to suppress its reverse mode, and cancelled proton-induced epigenetic regression of Atg7 that was caused by H3K4 and H4K20 tri-methylation via suppression of demethylase and H4K5 acetylation via suppression of nuclear HDAC3-HDAC4-emerin system. NM_026333 also attenuated proton-induced impaired formation of autolysosome, an increase in nuclear acetylated LC3 II, and acetylation of Atg7. These effects reappeared by NCX1 inhibitor. Furthermore, NCX1 inhibitor extended lifespan compared with vehicle-treatment in TG mice. This study will shed light on novel aging mechanism and provide implications in a target for anti-aging therapy.
KEYWORDS:
Anti-aging gene; Autophagy; Coupling factor 6; Epigenetics; Genomic instability; NCX1

Cocoa and Aging
A study finds that consuming a flavonoid in cocoa helped healthy mice delay skeletal muscle aging
two bowls of cocoa powder
By Dominique Ameroso
November 1, 2018
https://now.tufts.edu/articles/cocoa-and-aging
>>>>>>>>>>>>>>>>>>>
Dietary epicatechin improves survival and delays skeletal muscle degeneration in aged mice.
Si H, Wang X, Zhang L, Parnell LD, Admed B, LeRoith T, Ansah TA, Zhang L, Li J, Ordovás JM, Si H, Liu D, Lai CQ.
FASEB J. 2018 Aug 10:fj201800554RR. doi: 10.1096/fj.201800554RR. [Epub ahead of print]
PMID: 30096038
https://sci-hub.tw/10.1096/fj.201800554RR
Abstract
We recently reported that epicatechin, a bioactive compound that occurs naturally in various common foods, promoted general health and survival of obese diabetic mice. It remains to be determined whether epicatechin extends health span and delays the process of aging. In the present study, epicatechin or its analogue epigallocatechin gallate (EGCG) (0.25% w/v in drinking water) was administered to 20-mo-old male C57BL mice fed a standard chow. The goal was to determine the antiaging effect. The results showed that supplementation with epicatechin for 37 wk strikingly increased the survival rate from 39 to 69%, whereas EGCG had no significant effect. Consistently, epicatechin improved physical activity, delayed degeneration of skeletal muscle (quadriceps), and shifted the profiles of the serum metabolites and skeletal muscle general mRNA expressions in aging mice toward the profiles observed in young mice. In particular, we found that dietary epicatechin significantly reversed age-altered mRNA and protein expressions of extracellular matrix and peroxisome proliferator–activated receptor pathways in skeletal muscle, and reversed the age-induced declines of the nicotinate and nicotinamide pathway both in serum and skeletal muscle. The present study provides evidence that epicatechin supplementation can exert an antiaging effect, including an increase in survival, an attenuation of the aging-related deterioration of skeletal muscles, and a protection against the aging-related decline in nicotinate and nicotinamide metabolism.

[AlPater]

Probiotics probably aren't making you well, and they could make you sicker
A recent study suggests half of those who take probiotics just poop them right out
CBC Radio · November 2
https://www.cbc.ca/radio/quirks/probiotics-probably-aren-t-making-you-well-and-they-could-make-you-sicker-1.4887860
>>>>>>>>>>>>>>>>
Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features.
Zmora N, Zilberman-Schapira G, Suez J, Mor U, Dori-Bachash M, Bashiardes S, Kotler E, Zur M, Regev-Lehavi D, Brik RB, Federici S, Cohen Y, Linevsky R, Rothschild D, Moor AE, Ben-Moshe S, Harmelin A, Itzkovitz S, Maharshak N, Shibolet O, Shapiro H, Pevsner-Fischer M, Sharon I, Halpern Z, Segal E, Elinav E.
Cell. 2018 Sep 6;174(6):1388-1405.e21. doi: 10.1016/j.cell.2018.08.041.
PMID: 30193112
Abstract
Empiric probiotics are commonly consumed by healthy individuals as means of life quality improvement and disease prevention. However, evidence of probiotic gut mucosal colonization efficacy remains sparse and controversial. We metagenomically characterized the murine and human mucosal-associated gastrointestinal microbiome and found it to only partially correlate with stool microbiome. A sequential invasive multi-omics measurement at baseline and during consumption of an 11-strain probiotic combination or placebo demonstrated that probiotics remain viable upon gastrointestinal passage. In colonized, but not germ-free mice, probiotics encountered a marked mucosal colonization resistance. In contrast, humans featured person-, region- and strain-specific mucosal colonization patterns, hallmarked by predictive baseline host and microbiome features, but indistinguishable by probiotics presence in stool. Consequently, probiotics induced a transient, individualized impact on mucosal community structure and gut transcriptome. Collectively, empiric probiotics supplementation may be limited in universally and persistently impacting the gut mucosa, meriting development of new personalized probiotic approaches.
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT.
Suez J, Zmora N, Zilberman-Schapira G, Mor U, Dori-Bachash M, Bashiardes S, Zur M, Regev-Lehavi D, Ben-Zeev Brik R, Federici S, Horn M, Cohen Y, Moor AE, Zeevi D, Korem T, Kotler E, Harmelin A, Itzkovitz S, Maharshak N, Shibolet O, Pevsner-Fischer M, Shapiro H, Sharon I, Halpern Z, Segal E, Elinav E.
Cell. 2018 Sep 6;174(6):1406-1423.e16. doi: 10.1016/j.cell.2018.08.047.
PMID: 30193113
Abstract
Probiotics are widely prescribed for prevention of antibiotics-associated dysbiosis and related adverse effects. However, probiotic impact on post-antibiotic reconstitution of the gut mucosal host-microbiome niche remains elusive. We invasively examined the effects of multi-strain probiotics or autologous fecal microbiome transplantation (aFMT) on post-antibiotic reconstitution of the murine and human mucosal microbiome niche. Contrary to homeostasis, antibiotic perturbation enhanced probiotics colonization in the human mucosa but only mildly improved colonization in mice. Compared to spontaneous post-antibiotic recovery, probiotics induced a markedly delayed and persistently incomplete indigenous stool/mucosal microbiome reconstitution and host transcriptome recovery toward homeostatic configuration, while aFMT induced a rapid and near-complete recovery within days of administration. In vitro, Lactobacillus-secreted soluble factors contributed to probiotics-induced microbiome inhibition. Collectively, potential post-antibiotic probiotic benefits may be offset by a compromised gut mucosal recovery, highlighting a need of developing aFMT or personalized probiotic approaches achieving mucosal protection without compromising microbiome recolonization in the antibiotics-perturbed host.
KEYWORDS:
Probiotics; antibiotics; microbiome

[AlPater]

Association between human herpes virus seropositivity and frailty in the elderly: A systematic review and meta-analysis.
Araújo Carvalho AC, Tavares Mendes ML, Santos VS, Tanajura DM, Prado Nunes MA, Saquete Martins-Filho PR.
Ageing Res Rev. 2018 Oct 31. pii: S1568-1637(18)30125-9. doi: 10.1016/j.arr.2018.10.009. [Epub ahead of print] Review.
PMID: 30391341
Abstract
Frailty is an emerging geriatric syndrome characterized by decreased physiologic reserve and increased vulnerability to environmental factors. Several studies have examined the association between persistent cytomegalovirus (CMV) infection and poor clinical outcomes in the elderly, but the results are often contradictory. Here, we performed a systematic review and meta-analysis to analyze the association between human herpesvirus seropositivity [CMV, Epstein-Barr virus (EBV), Varicella zoster virus (VZV), and Herpes simplex virus (HSV)] and frailty in elderly people. Searches were performed in PubMed, SCOPUS, Lilacs, IBECS, and Web of Science databases. We used the odds ratio (OR) as a measure of the association between herpesvirus infections and frailty. Summary estimates were calculated using random-effects models. Six studies were included in the present systematic review. The data from 2559 elderly subjects were analyzed; 1571 of the subjects had ages between 60 and 79 years, and 988 of the subjects were older than 80. We found an association between CMV seropositivity and frailty in the elderly aged 60-79 years (OR 2.33, CI 95% 1.48-3.67) but not in the oldest-old subjects (OR 0.67, CI 95% 0.42-1.05). Moreover, no association was found between EBV, VZV, and HSV infections and frailty. Current evidence suggests an association between CMV seropositivity and frailty in individuals aged 60-79 years old.
KEYWORDS:
elderly; frailty; human herpesvirus

Dose-response relationship between docosahexaenoic acid (DHA) intake and lower rates of early preterm birth, low birth weight and very low birth weight.
Carlson SE, Gajewski BJ, Alhayek S, Colombo J, Kerling EH, Gustafson KM.
Prostaglandins Leukot Essent Fatty Acids. 2018 Nov;138:1-5. doi: 10.1016/j.plefa.2018.09.002. Epub 2018 Sep 20.
PMID: 30392575
Abstract
As previously reported, intention-to-treat findings from our phase III randomized clinical trial found that a supplement of 600 mg docosahexaenoic acid (DHA)/day during the last half of pregnancy reduced the incidence of early preterm birth (ePTB, <34 weeks gestation) and very low birth weight (VLBW < 1500 g) offspring. Given the potentially immense clinical significance of these findings, the goal of this secondary analysis was to (1) identify maternal characteristics related with capsule intake (i.e. DHA dose exposure) and (2) determine if DHA dose was associated with low (<2500 g) and very low birth weight after controlling for any relevant maternal characteristics. Three hundred forty-five pregnant mothers were recruited from hospitals in the Kansas City metropolitan area between 2006 and 2011. Most participants (n = 299) were from the phase III trial mentioned above, but we also included 46 participants from a second smaller, randomized trial that utilized an identical intervention design and was conducted concurrent to the larger trial. Both trials assigned participants to either 3 daily capsules of vegetable oil without DHA (n = 169) or 3 daily capsules of 200 mg DHA each (n = 176). Total capsules consumed was recorded by pharmacy supervised capsule count or participant self-report when needed. Maternal age, education, race and gestational age at delivery as well as infant birth weight were available for both trials. A Bayesian linear model indicated capsule intake increased with maternal age (p = 0.0100) and years of education (p = 0.0002). A Bayesian bivariate mixture-model associated capsule intake with simultaneous lower probability of ePTB, low birth weight (LBW, <2500 g) and VLBW (p = 0.0327). This, in conjunction with the positive findings in the clinical trial, support the need for future research to examine intervention methods to improve capsule compliance strategies in younger and less educated mothers.
KEYWORDS:
Birth weight; Compliance; Docosahexaenoic acid; Placebo; Preterm birth

mTOR Signaling Pathway and Protein Synthesis: From Training to Aging and Muscle Autophagy.
Ilha J, do Espírito-Santo CC, de Freitas GR.
Adv Exp Med Biol. 2018;1088:139-151. doi: 10.1007/978-981-13-1435-3_7.
PMID: 30390251
https://sci-hub.tw/10.1007/978-981-13-1435-3_7
Abstract
In muscle tissue there is a balance between the processes muscle synthesis and degradation. The mammalian target of rapamycin (mTOR) signaling pathway plays a critical role in regulating protein synthesis in order to maintain muscular protein turnover and trophism. Studies have shown that both down- and upregulation mechanisms are involved in this process in a manner dependent on stimulus and cellular conditions. Additionally, mTOR signaling has recently been implicated in several physiological conditions related to cell survival, such as self-digestion (autophagy), energy production, and the preservation of cellular metabolic balance over the lifespan. Here we briefly describe the mTOR structure and its regulatory protein synthesis pathway. Furthermore, the role of mTOR protein in autophagy, aging, and mitochondrial function in muscle tissue is presented.
KEYWORDS:
Muscle autophagy; Muscle trophism; Muscular synthesis; mTOR pathway

Effect of a Lifestyle Intervention Program With Energy-Restricted Mediterranean Diet and Exercise on Weight Loss and Cardiovascular Risk Factors: One-Year Results of the PREDIMED-Plus Trial.
Salas-Salvadó J, Díaz-López A, Ruiz-Canela M, Basora J, Fitó M, Corella D, Serra-Majem L, Wärnberg J, Romaguera D, Estruch R, Vidal J, Martínez JA, Arós F, Vázquez C, Ros E, Vioque J, López-Miranda J, Bueno-Cavanillas A, Tur JA, Tinahones FJ, Martín V, Lapetra J, Pintó X, Daimiel L, Delgado-Rodríguez M, Matía P, Gómez-Gracia E, Díez-Espino J, Babio N, Castañer O, Sorlí JV, Fiol M, Zulet MÁ, Bulló M, Goday A, Martínez-González MA; PREDIMED-Plus investigators.
Diabetes Care. 2018 Nov 2. pii: dc180836. doi: 10.2337/dc18-0836. [Epub ahead of print]
PMID: 30389673
https://sci-hub.tw/10.2337/dc18-0836
Abstract
OBJECTIVE:
The long-term impact of intentional weight loss on cardiovascular events remains unknown. We describe 12-month changes in body weight and cardiovascular risk factors in PREvención con DIeta MEDiterránea (PREDIMED)-Plus, a trial designed to evaluate the long-term effectiveness of an intensive weight-loss lifestyle intervention on primary cardiovascular prevention.
RESEARCH DESIGN AND METHODS:
Overweight/obese adults with metabolic syndrome aged 55-75 years (n = 626) were randomized to an intensive weight-loss lifestyle intervention based on an energy-restricted Mediterranean diet, physical activity promotion, and behavioral support (IG) or a control group (CG). The primary and secondary outcomes were changes in weight and cardiovascular risk markers, respectively.
RESULTS:
Diet and physical activity changes were in the expected direction, with significant improvements in IG versus CG. After 12 months, IG participants lost an average of 3.2 kg vs. 0.7 kg in the CG (P < 0.001), a mean difference of -2.5 kg (95% CI -3.1 to -1.9). Weight loss ≥5% occurred in 33.7% of IG participants compared with 11.9% in the CG (P < 0.001). Compared with the CG, cardiovascular risk factors, including waist circumference, fasting glucose, triglycerides, and HDL-cholesterol, significantly improved in IG participants (P < 0.002). Reductions in insulin resistance, HbA1c, and circulating levels of leptin, interleukin-18, and MCP-1 were greater in IG than CG participants (P < 0.05). IG participants with prediabetes/diabetes significantly improved glycemic control and insulin sensitivity, along with triglycerides and HDL-cholesterol levels compared with their CG counterparts.
CONCLUSIONS:
PREDIMED-Plus intensive lifestyle intervention for 12 months was effective in decreasing adiposity and improving cardiovascular risk factors in overweight/obese older adults with metabolic syndrome, as well as in individuals with or at risk for diabetes.

Britain's deprived areas have five times as many fast food shops as rich areas.
Wise J.
BMJ. 2018 Nov 2;363:k4661. doi: 10.1136/bmj.k4661. No abstract available.
PMID: 30389693
http://sci-hub.tw/10.1136/bmj.k4661

Effects of branched chain amino acid supplementation on patient care outcomes in adults and children with liver cirrhosis: A systematic review.
Ooi PH, Gilmour SM, Yap J, Mager DR.
Clin Nutr ESPEN. 2018 Dec;28:41-51. doi: 10.1016/j.clnesp.2018.07.012. Epub 2018 Aug 14. Review.
PMID: 30390892
Abstract
BACKGROUND & AIMS:
Malnutrition is highly prevalent in chronic liver disease (CLD) due to alterations in nutrient utilization, malabsorption and poor intake. Low serum concentrations of branched chain amino acids (BCAA) in the presence of elevated aromatic acid concentrations is commonly observed in adult and children with liver cirrhosis and is associated with malnutrition and other adverse patient outcomes. The efficacy of BCAA supplementation has not been well established in adults and children with CLD. The purpose of this review was to critically evaluate the literature regarding the impact of BCAA supplementation related to changes in body composition, muscle strength, liver biomarkers, medical and hepatic complications (hepatic encephalopathy (HE), ascites, edema) and patient care outcomes (event free survival, health related quality of life, length of hospitalization).
METHODS:
A total of 40 articles retrieved from PubMed or Web of Science databases (1989-2017) were included.
RESULTS:
BCAA supplementation may be beneficial in improving muscle strength, ascites and edema with potential clinically significant improvements in HE in adult liver patients. In children, limited data have shown that BCAA supplementation may exert favourable effects on weight, fat mass, fat free mass and serum albumin level.
CONCLUSIONS:
Heterogeneity of study findings attributed to variability in BCAA dose (total, relative proportions), duration, disease severity and lack of uniformity in tools used for assessing patient outcomes limit overall conclusions. Longitudinal studies examining the efficacy of BCAA supplementation as a therapeutic treatment of malnutrition in chronic liver disease is warranted.
KEYWORDS:
Adults; Body composition; Branched chain amino acids; Children; Liver disease; Patient care outcomes

No association between dietary markers and incident hypertension in a population-based sample.
Quinteiros Fidalgo AS, Vollenweider P, Marques-Vidal P.
Clin Nutr ESPEN. 2018 Dec;28:208-213. doi: 10.1016/j.clnesp.2018.07.013. Epub 2018 Aug 16.
PMID: 30390882
https://sci-hub.tw/10.1016/j.clnesp.2018.07.013
Abstract
BACKGROUND/AIM:
Many trials have shown that dietary interventions reduce the incidence of hypertension. Whether these findings also apply in the general population is debated. We assessed the association between dietary markers and incidence of hypertension.
DESIGN:
prospective observational study.
METHODS:
Population-based study conducted between April 2009 and April 2017 in Lausanne, Switzerland. 2079 participants (60.6% women, 53.9 ± 9.0 years, age range 40-80), devoid of hypertension at baseline, were followed for a median time of 63 months. Hypertension was defined as systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg or anti-hypertensive medication. Self-reported dietary intake was assessed using a food frequency questionnaire. Analysis was conducted using logistic regression.
RESULTS:
370 participants (17.8%) developed hypertension. On bivariate analysis, no association was found between all food items, dietary scores and compliance to dietary guidelines and incident hypertension. Similar findings were observed after multivariable analysis.
CONCLUSION:
Over a period of 5 years, one sixth of the Swiss population aged 40 to 80 developed hypertension. No association was found between dietary markers and incident hypertension. Current dietary behaviours are insufficient to prevent hypertension in the general population.
KEYWORDS:
Dietary markers; Hypertension; Incidence; Prospective study; Switzerland

Association between body mass index and all-cause death in Japanese population: pooled individual participant data analysis of 13 cohort studies.
Hozawa A, Hirata T, Yatsuya H, Murakami Y, Kuriyama S, Tsuji I, Sugiyama D, Satoh A, Tanaka-Mizuno S, Miura K, Ueshima H, Okamura T.
J Epidemiol. 2018 Nov 3. doi: 10.2188/jea.JE20180124. [Epub ahead of print]
PMID: 30393269
https://www.jstage.jst.go.jp/article/jea/advpub/0/advpub_JE20180124/_pdf/-char/en
Abstract
BACKGROUND:
To investigate the optimal values of BMI for the lowest risk of all-cause death and whether the optimal BMI differs according to smoking status in large-scale pooled analysis of 13 Japanese cohorts.
METHODS:
Data from 179,987 participants of 13 well-qualified cohort studies conducted throughout Japan were used for our analysis. A cohort-stratified Cox proportional hazard model was used. P values for interactions were calculated based on the cross product of BMI and age, sex, or smoking status.
RESULTS:
In the entire study population, all-cause mortality risk were lowest when the BMI was 22.0-24.9 kg/m2. This was also the case for selected healthy participants (never smoked, baseline total cholesterol level ≥4.1 mmol/L; the first 5 years of follow-up data were excluded). No effect modification of age, sex, or smoking status was observed. Regardless of their BMI, never smokers always had a lower all-cause mortality risk than did current smokers even with an ideal BMI in terms of mortality risk.
CONCLUSION:
A BMI of 22-24.9 kg/m2 correlated with the lowest risk of mortality, regardless of whether all participants or selected healthy participants were analyzed. The fact that smoking was more strongly associated with mortality than did obesity would emphasize the urgency for effective anti-smoking programs.
KEYWORDS:
All-cause mortality; Body Mass Index; Pooled Analyses; Prospective studies

[AlPater]

Nutritional Interventions and Cognitive-related Outcomes in Patients with Late-life Cognitive Disorders: A Systematic Review.
Solfrizzi V, Agosti P, Lozupone M, Custodero C, Schilardi A, Valiani V, Santamato A, Sardone R, Dibello V, Di Lena L, Stallone R, Ranieri M, Bellomo A, Greco A, Daniele A, Seripa D, Sabbà C, Logroscino G, Panza F.
Neurosci Biobehav Rev. 2018 Nov 2. pii: S0149-7634(18)30507-4. doi: 10.1016/j.neubiorev.2018.10.022. [Epub ahead of print] Review.
PMID: 30395922
https://sci-hub.tw/10.1016/j.neubiorev.2018.10.022
Abstract
There have been a large number of observational studies on the impact of nutrition on neuroprotection, however, there was a lack of evidence from randomized clinical trials (RCTs). In the present systematic review, from the 32 included RCTs published in the last four years (2014-2017) in patients aged 60 years and older with different late-life cognitive disorders, nutritional intervention through medical food/nutraceutical supplementation and multidomain approach improved magnetic resonance imaging findings and other cognitive-related biomarkers, but without clear effect on cognition in mild Alzheimer's disease (AD) and mild cognitive impairment (MCI). Antioxidant-rich foods (nuts, grapes, cherries) and fatty acid supplementation, mainly n-3 polyunsaturated fatty acids (PUFA), improved specific cognitive domains and cognitive-related outcomes in MCI, mild-to-moderate dementia, and AD. Antioxidant vitamin and trace element supplementations improved only cognitive-related outcomes and biomarkers, high-dose B vitamin supplementation in AD and MCI patients improved cognitive outcomes in the subjects with a high baseline plasma n-3 PUFA, while folic acid supplementation had positive impact on specific cognitive domains in those with high homocysteine.
KEYWORDS:
Alzheimer’s disease; dementia; macronutrients; medical food; micronutrients; nutraceuticals

Association between physical activity, occupational sitting time and mortality in a general population: An 18-year prospective survey in Tanushimaru, Japan.
Sakaue A, Adachi H, Enomoto M, Fukami A, Kumagai E, Nakamura S, Nohara Y, Kono S, Nakao E, Morikawa N, Tsuru T, Hamamura H, Yoshida N, Fukumoto Y.
Eur J Prev Cardiol. 2018 Nov 5:2047487318810020. doi: 10.1177/2047487318810020. [Epub ahead of print]
PMID: 30396293
https://sci-hub.tw/https://journals.sagepub.com/doi/10.1177/2047487318810020
Abstract
AIMS:
It is well known that a decline in physical activity is associated with an increase of all-cause death including cardiovascular events and cancer. Few studies have examined the association between occupational sitting time and mortality. Therefore, we investigated this issue in a general population.
METHODS:
Physical activity and occupational sitting time were measured using the Baecke physical activity questionnaire in 1999. The questionnaire generated indices in three physical activity categories: work, sport and leisure-time. A total physical activity index was calculated by adding these three indices. The Baecke physical activity questionnaire was able to evaluate occupational sitting time. Hazard ratios and 95% confidence intervals (CIs) were calculated using Cox's proportional hazard regression models.
RESULTS:
We enrolled a total of 1680 participants, who were followed up for 15.9 ± 3.8 years. The final follow-up rate was 93%. During the follow-up period, 397 subjects died. A significant inverse association ( p < 0.0001) was found between physical activity and mortality after adjustment for age and sex. Compared with lower levels of physical activity, the adjusted hazard ratio for mortality at higher levels of physical activity was 0.85 (95% CI: 0.78-0.92). Longer occupational sitting time was also significantly associated with higher mortality ( p < 0.01). The adjusted hazard ratio for mortality at longer occupational sitting time was 1.16 (95% CI: 1.05-1.27). These findings were observed in males, but not in females.
CONCLUSIONS:
Our data demonstrated that higher levels of physical activity are associated with a reduced risk of cancer and cardiovascular death. Further, longer occupational sitting time is associated with increased mortality.
KEYWORDS:
Physical activity; epidemiology; mortality; sitting time

Association of Change in Cardiovascular Risk Factors With Incident Cardiovascular Events.
van Sloten TT, Tafflet M, Périer MC, Dugravot A, Climie RED, Singh-Manoux A, Empana JP.
JAMA. 2018 Nov 6;320(17):1793-1804. doi: 10.1001/jama.2018.16975.
PMID: 30398604
Abstract
IMPORTANCE:
There is consistent evidence of the association between ideal cardiovascular health and lower incident cardiovascular disease (CVD); however, most studies used a single measure of cardiovascular health.
OBJECTIVE:
To examine how cardiovascular health changes over time and whether these changes are associated with incident CVD.
DESIGN, SETTING, AND PARTICIPANTS:
Prospective cohort study in a UK general community (Whitehall II), with examinations of cardiovascular health from 1985/1988 (baseline) and every 5 years thereafter until 2015/2016 and follow-up for incident CVD until March 2017.
EXPOSURES:
Using the 7 metrics of the American Heart Association (nonsmoking; and ideal levels of body mass index, physical activity, diet, blood pressure, fasting blood glucose, and total cholesterol), participants with 0 to 2, 3 to 4, and 5 to 7 ideal metrics were categorized as having low, moderate, and high cardiovascular health. Change in cardiovascular health over 10 years between 1985/1988 and 1997/1999 was considered.
MAIN OUTCOME AND MEASURE:
Incident CVD (coronary heart disease and stroke).
RESULTS:
The study population included 9256 participants without prior CVD (mean [SD] age at baseline, 44.8 [6.0] years; 2941 [32%] women), of whom 6326 had data about cardiovascular health change. Over a median follow-up of 18.9 years after 1997/1999, 1114 incident CVD events occurred. In multivariable analysis and compared with individuals with persistently low cardiovascular health (consistently low group, 13.5% of participants; CVD incident rate per 1000 person-years, 9.6 [95% CI, 8.4-10.9]), there was no significant association with CVD risk in the low to moderate group (6.8% of participants; absolute rate difference per 1000 person-years, -1.9 [95% CI, -3.9 to 0.1]; HR, 0.84 [95% CI, 0.66-1.08]), the low to high group, (0.3% of participants; absolute rate difference per 1000 person-years, -7.7 [95% CI, -11.5 to -3.9]; HR, 0.19 [95% CI, 0.03-1.35]), and the moderate to low group (18.0% of participants; absolute rate difference per 1000 person-years, -1.3 [95% CI, -3.0 to 0.3]; HR, 0.96 [95% CI, 0.80-1.15]). A lower CVD risk was observed in the consistently moderate group (38.9% of participants; absolute rate difference per 1000 person-years, -4.2 [95% CI, -5.5 to -2.8]; HR, 0.62 [95% CI, 0.53-0.74]), the moderate to high group (5.8% of participants; absolute rate difference per 1000 person-years, -6.4 [95% CI, -8.0 to -4.7]; HR, 0.39 [95% CI, 0.27-0.56]), the high to low group (1.9% of participants; absolute rate difference per 1000 person-years, -5.3 [95% CI, -7.8 to -2.8]; HR, 0.49 [95% CI, 0.29-0.83]), the high to moderate group (9.3% of participants; absolute rate difference per 1000 person-years, -4.5 [95% CI, -6.2 to -2.9]; HR, 0.66 [95% CI, 0.51-0.85]), and the consistently high group (5.5% of participants; absolute rate difference per 1000 person-years, -5.6 [95% CI, -7.4 to -3.9]; HR, 0.57 [95% CI, 0.40-0.80]).
CONCLUSIONS AND RELEVANCE:
Among a group of participants without CVD who received follow-up over a median 18.9 years, there was no consistent relationship between direction of change in category of a composite metric of cardiovascular health and risk of CVD.

Cruciferous vegetable intake and colorectal cancer risk: Japan public health center-based prospective study.
Mori N, Sawada N, Shimazu T, Yamaji T, Goto A, Takachi R, Ishihara J, Iwasaki M, Inoue M, Tsugane S; ; the JPHC Study Group.
Eur J Cancer Prev. 2018 Nov 5. doi: 10.1097/CEJ.0000000000000491. [Epub ahead of print]
PMID: 30399043
Abstract
We aimed to assess the association between cruciferous vegetable intake and colorectal cancer (CRC) development among Japanese adults aged between 45 and 74 years in the Japan Public Health Center-based Prospective Study. During 1 325 853 person-years of follow-up, 2612 CRC cases were identified. The association of cruciferous vegetable intake with CRC risk was assessed using a Cox proportional hazard regression model to compute hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for potential confounders. No significant association was observed between the highest cruciferous vegetable intake quartile (compared with the lowest) and CRC risk in men (multivariate HRs: 1.08; 95% CI: 0.91, 1.29) and women (multivariate HRs: 0.99; 95% CI: 0.80, 1.22) and its subsites. Women showed a marginal negative association between cruciferous vegetable intake and the risk of colon cancer (CC) after excluding participants who developed CC in the first 3 years of follow-up (P for trend=0.08); a positive association was found with proximal CC in men. Cruciferous vegetable intake does not have a significant association with CRC risk in the Japanese general population.
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Cruciferous vegetables and risk of colorectal neoplasms: a systematic review and meta-analysis.
Tse G, Eslick GD.
Nutr Cancer. 2014;66(1):128-39. doi: 10.1080/01635581.2014.852686. Epub 2013 Dec 16. Review.
PMID: 24341734
https://sci-hub.tw/10.1080/01635581.2014.852686
Abstract
Evidence shows cruciferous vegetables exhibit chemoprotective properties, commonly attributed to their rich source of isothiocyanates. However, epidemiological data examining the association between cruciferous vegetable intake and colorectal neoplasms have been inconclusive. This meta-analysis examines the epidemiological evidence to characterize the association between cruciferous vegetable intake and risk of developing colorectal neoplasms. Thirty-three articles were included in the meta-analysis after a literature search of electronic databases. Subgroup analysis for individual cruciferae types (n = 8 studies) and GST polymorphism (n = 8 studies) were performed. Pooled adjusted odds ratios (ORs) comparing highest and lowest categories of dietary pattern scores were calculated. Results show a statistically significant inverse association between cruciferous vegetable intake and colon cancer [OR = 0.84; 95% confidence interval (CI): 0.72-0.98; P value heterogeneity < 0.001]. Broccoli in particular exhibited protective benefits against colorectal (CRC) neoplasms (OR = 0.80; 95% CI: 0.65-0.99; P value heterogeneity = 0.02). Stratification by GST genotype reveals that the GSTT1 null genotype confers a reduction in CRC risk (OR = 0.78; 95% CI: 0.64-0.95; P value heterogeneity = 0.32). This study provides support to the hypothesis that cruciferous vegetable intake protects against cancer of the colon. This study also demonstrates the significance of gene-diet interactions and the importance of assessing individual cruciferous vegetables.

[AlPater]

Mediterranean diet and its components in relation to all-cause mortality: meta-analysis.
Eleftheriou D, Benetou V, Trichopoulou A, La Vecchia C, Bamia C.
Br J Nutr. 2018 Nov;120(10):1081-1097. doi: 10.1017/S0007114518002593.
PMID: 30401007
https://sci-hub.tw/https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/mediterranean-diet-and-its-components-in-relation-to-allcause-mortality-metaanalysis/81EB9EF4D5B7AD5BC3ADC8AEC86371E1
Abstract
The beneficial association of the Mediterranean diet (MedDiet) with longevity has been consistently demonstrated, but the associations of MedDiet components have not been accordingly evaluated. We performed an updated meta-analysis of prospective cohort studies published up to 31 December 2017, to quantify the association of adherence to MedDiet, expressed as an index/score (MDS) and of its components with all-cause mortality. We estimated summary relative risks (SRR) and 95 % CI using random effects models. On the basis of thirty studies (225 600 deaths), SRR for the study-specific highest/lowest and per 1sd MDS increment were 0·79 (95 % CI 0·77, 0·81, Ι 2=42 %, P-heterogeneity 0·02) and 0·92 (95 % CI 0·90, 0·94, Ι 2 56 %, P-heterogeneity <0·01), respectively. Inversely, statistically significant associations were evident in stratified analyses by country, MDS range and publication year, with some evidence for heterogeneity across countries overall (P-heterogeneity 0·011), as well as across European countries (P=0·018). Regarding MDS components, relatively stronger and statistically significant inverse associations were highlighted for moderate/none-excessive alcohol consumption (0·86, 95 % CI 0·77, 0·97) and for above/below-the-median consumptions of fruit (0·88, 95 % CI 0·83, 0·94) and vegetables (0·94, 95 % CI 0·89, 0·98), whereas a positive association was apparent for above/below-the-median intake of meat (1·07, 95 % CI 1·01, 1·13). Our meta-analyses confirm the inverse association of MedDiet with mortality and highlight the dietary components that influence mostly this association. Our results are important for better understanding the role of MedDiet in health and proposing dietary changes to effectively increase adherence to this healthy dietary pattern.
KEYWORDS:
HR hazard ratio; MDS Mediterranean diet score; MedDiet Mediterranean diet; RR relative risk.; Mediterranean diet; Meta-analyses; Mortality; Reviews

Dietary Intake of Anti-Oxidant Vitamins A, C, and E Is Inversely Associated with Adverse Cardiovascular Outcomes in Chinese-A 22-Years Population-Based Prospective Study.
Lee CH, Chan RSM, Wan HYL, Woo YC, Cheung CYY, Fong CHY, Cheung BMY, Lam TH, Janus E, Woo J, Lam KSL.
Nutrients. 2018 Nov 4;10(11). pii: E1664. doi: 10.3390/nu10111664.
PMID: 30400367
Abstract
Background: Conflicting and population-dependent findings have been reported from epidemiological studies on the associations of dietary intake of anti-oxidant vitamins with cardiovascular events. We investigated the prospective relationship between dietary intake of anti-oxidant vitamins and incident adverse cardiovascular outcomes amongst Hong Kong Chinese. Methods: In this prospective population-based study, baseline dietary intake of anti-oxidant vitamins (A, C, and E) were assessed using a food frequency questionnaire in 875 Chinese participants from the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS) in 1995⁻1996. The adjusted hazard ratio (HR) of incident adverse cardiovascular outcomes, defined as the first recorded diagnosis of cardiovascular deaths, non-fatal myocardial infarction or non-fatal stroke, and coronary or other arterial revascularizations, was calculated per unit intake of each vitamin using multivariable Cox regression. Results: Over a median follow-up of 22 years, 85 participants (9.7%) developed adverse cardiovascular outcomes. Dietary intakes of vitamin A, C, and E were independently and inversely associated with incident adverse cardiovascular outcomes (HR 0.68, 95%CI 0.53⁻0.88, p = 0.003 for vitamin A; HR 0.66, 95%CI 0.52⁻0.85, p = 0.001 for vitamin C; and HR 0.57, 95%CI 0.38⁻0.86, p = 0.017 for vitamin E) after adjustments for conventional cardiovascular risk factors at baseline. Conclusions: Dietary intakes of anti-oxidant vitamins A, C, and E reduced the risk of adverse cardiovascular outcomes in Hong Kong Chinese.
KEYWORDS:
adverse cardiovascular outcomes; anti-oxidant; chinese; prediction model; vitamin A; vitamin C; vitamin E

Longitudinal Association between n-3 Long-Chain Polyunsaturated Fatty Acid Intake and Depressive Symptoms: A Population-Based Cohort Study in Japan.
Horikawa C, Otsuka R, Kato Y, Nishita Y, Tange C, Rogi T, Kawashima H, Shibata H, Ando F, Shimokata H.
Nutrients. 2018 Nov 3;10(11). pii: E1655. doi: 10.3390/nu10111655.
PMID: 30400311
Abstract
It remains unclear whether n-3 long-chain polyunsaturated fatty acids (LCPUFA) have a preventive effect on depression in the general population. This study investigated the longitudinal association between n-3 LCPUFA intake and depressive symptoms in community-dwelling Japanese participants. The participants were aged 40⁻79 years at baseline in the cohort study; wherein examinations; including the assessment of depressive symptoms and nutritional status; were biennially conducted from 1997 to 2012. The subjects (n = 2335) who had a Center for Epidemiologic Studies Depression Scale (CES-D) score < 16 at the first examination and who participated in the follow-up study at least once were included in the analysis. The follow-up end point was the first onset (CES-D ≥ 16) or the last examination participation. Hazard ratios (95% CIs) for CES-D ≥ 16 were estimated using the adjusted Cox proportional hazards model. Overall; 22.1% participants showed depressive symptoms during follow-up (average; 8.1 years). Compared with the lowest tertile; the highest HR for EPA was 0.74 (0.60⁻0.93), and highest and middle HRs for DHA were 0.79 (0.63⁻0.98) and 0.80 (0.65⁻0.99) (P for trend = 0.009 and 0.032), respectively. Among populations with high fish consumption; higher n-3 LCPUFA intake may be associated with a low risk of depressive symptoms.
KEYWORDS:
Japanese; NILS-LSA; cohort; community-dwelling; depressive symptoms; n-3 LCPUFA

Healthy Dietary Changes in Midlife Are Associated with Reduced Dementia Risk Later in Life.
Sindi S, Kåreholt I, Eskelinen M, Hooshmand B, Lehtisalo J, Soininen H, Ngandu T, Kivipelto M.
Nutrients. 2018 Nov 3;10(11). pii: E1649. doi: 10.3390/nu10111649.
PMID: 30400288
https://www.mdpi.com/2072-6643/10/11/1649/htm
Abstract
Diet is an important modifiable lifestyle factor related to dementia risk. Yet, the role of midlife dietary changes is unclear. The goal is to investigate whether midlife healthy dietary changes are associated with late-life dementia risk. Data were collected within the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) population-based cohort study (n = 2000) (mean baseline age = 56 years). Participants returned for two late-life re-examinations (mean age = 70 and 78 years). Self-reported midlife diet was measured in a sub-sample (n = 341) (mean total follow-up = 16.8 years). Changes in specific dietary components (fats, vegetables, sugar, salt) were measured in midlife. Dementia diagnoses were ascertained with detailed examinations. Analyses adjusted for potential confounders. Total midlife healthy dietary changes (improving quality of fats, increasing vegetables, decreasing sugar and salt) were associated with a reduced risk of dementia (fully adjusted odds ratio (OR) 0.41, 95% confidence interval (CI) = 0.20⁻0.85). In contrast, when each factor was assessed individually, associations were not significant. This study is the first to show that beneficial midlife dietary changes are associated with a reduced dementia risk later in life. The results highlight the importance of targeting dietary patterns, where various food items may have synergistic effects.
KEYWORDS:
dementia; diet; dietary change; midlife protective factors; public health

Habitual Tea Consumption and Risk of Fracture in 0.5 Million Chinese Adults: A Prospective Cohort Study.
Shen Q, Yu C, Guo Y, Bian Z, Zhu N, Yang L, Chen Y, Luo G, Li J, Qin Y, Chen J, Chen Z, Lv J, Li L; China Kadoorie Biobank Collaborative Group.
Nutrients. 2018 Nov 2;10(11). pii: E1633. doi: 10.3390/nu10111633.
PMID: 30400175
https://www.mdpi.com/2072-6643/10/11/1633/htm
Abstract
BACKGROUND:
Tea consumption may have favorable effects on risk of fracture. However, little is known about such association in Chinese adults. The aim of this study was to examine the association between tea consumption and risk of hospitalized fracture in Chinese adults.
METHODS:
The present study included 453,625 participants from the China Kadoorie Biobank (CKB). Tea consumption was self-reported at baseline. Hospitalized fractures were ascertained through linkage with local health insurance claim databases.
THE RESULTS:
During a median of 10.1 years of follow-up, we documented 12,130 cases of first-time any fracture hospitalizations, including 1376 cases of hip fracture. Compared with never tea consumers, daily tea consumption was associated with lower risk of any fracture (hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.83, 0.93). Statistically significant reduced risk of hip fracture was shown among daily consumers who most commonly drank green tea (HR: 0.80; 95% CI: 0.65, 0.97) and those who had drunk tea for more than 30 years (HR: 0.68; 95% CI: 0.52, 0.87). Our conclusions: Habitual tea consumption was associated with moderately decreased risk of any fracture hospitalizations. Participants with decades of tea consumption and those who preferred green tea were also associated with lower risk of hip fracture.
KEYWORDS:
cohort study; fracture; tea consumption

Are Raw Brassica Vegetables Healthier Than Cooked Ones? A Randomized, Controlled Crossover Intervention Trial on the Health-Promoting Potential of Ethiopian Kale.
Schlotz N, Odongo GA, Herz C, Waßmer H, Kühn C, Hanschen FS, Neugart S, Binder N, Ngwene B, Schreiner M, Rohn S, Lamy E.
Nutrients. 2018 Nov 2;10(11). pii: E1622. doi: 10.3390/nu10111622.
PMID: 30400138
https://www.mdpi.com/2072-6643/10/11/1622/htm
Abstract
The present human intervention trial investigated the health-promoting potential of B. carinata, with a focus on effects of thermal processing on bioactivity. Twenty-two healthy subjects consumed a B. carinata preparation from raw (allyl isothiocyanate-containing) or cooked (no allyl isothiocyanate) leaves for five days in a randomized crossover design. Peripheral blood mononuclear cells were exposed to aflatoxin B1 (AFB1), with or without metabolic activation using human S9 mix, and subsequently analyzed for DNA damage using the comet assay. Plasma was analyzed for total antioxidant capacity and prostaglandin E₂ (PGE₂) levels. Cooked B. carinata significantly reduced DNA damage induced by AFB1 as compared to baseline levels (+S9 mix: 35%, -S9 mix: 33%, p ≤ 0.01, respectively). Raw B. carinata only reduced DNA damage by S9-activated AFB1 by 21% (p = 0.08). PGE₂ plasma levels were significantly reduced in subjects after consuming raw B. carinata. No changes in plasma antioxidant capacity were detectable. A balanced diet, including raw and cooked Brassica vegetables, might be suited to fully exploit the health-promoting potential. These results also advocate the promotion of B. carinata cultivation in Eastern Africa as a measure to combat effects of unavoidable aflatoxin exposure.
KEYWORDS:
Brassica vegetables; aflatoxin B1; anti-genotoxicity; cancer chemoprevention; comet assay

White blood cell count and all-cause and cause-specific mortality in the Guangzhou biobank cohort study.
Wang T, Jiang CQ, Xu L, Zhang WS, Zhu F, Jin YL, Thomas GN, Cheng KK, Lam TH.
BMC Public Health. 2018 Nov 6;18(1):1232. doi: 10.1186/s12889-018-6073-6.
PMID: 30400967
https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-018-6073-6
Abstract
BACKGROUND:
Several studies have shown positive associations between higher WBC count and deaths from all-causes, CHD, stroke and cancer among occidental populations or developed countries of Asia. No study on the association of WBC count with all-cause and cause-specific mortality in Chinese populations was reported. We studied this using prospective data from a large Chinese cohort.
METHODS:
We used prospective data from the Guangzhou Biobank Cohort Study (GBCS), a total of 29,925 participants in present study. A Cox proportional hazards regression model was used to estimate the hazard ratios (HR) and 95% confidence interval (CI).
RESULTS:
The hazard ratios (HR) for all-cause, CHD, and respiratory disease mortality for the highest decile of WBC count (women > 8.2 × 109/L; men > 8.8 × 109/L) was 1.83 (95% confidence interval (CI) 1.54, 2.17), 3.02 (95% CI 1.84, 4.98) and 2.52 (95% CI 1.49, 4.27), respectively, after adjusting for multiple potential confounders. The associations were similar when deaths during the first 2 years of follow-up were excluded. After further adjusting for pulmonary function, the highest decile of WBC count was associated with 90% higher risk of respiratory disease mortality (HR 1.90, 95% CI 1.08, 3.33). No evidence for an association between higher WBC count and cancer mortality was found. Sub-type analysis showed that only granulocyte count remained significantly predictive of all-cause, CHD, and respiratory disease mortality.
CONCLUSIONS:
Elevated WBC, specifically granulocyte, count was associated with all-cause, CHD and respiratory mortality in southern Chinese. Further investigation is warranted to clarify whether decreasing inflammation would attenuate WBC count associated mortality.
KEYWORDS:
All-cause mortality; Cause-specific mortality; Granulocyte count; Prospective cohort study; White blood cell count

High sodium intake increases blood pressure and risk of kidney disease. From the Science of Salt: A regularly updated systematic review of salt and health outcomes (August 2016 to March 2017).
Malta D, Petersen KS, Johnson C, Trieu K, Rae S, Jefferson K, Santos JA, Wong MMY, Raj TS, Webster J, Campbell NRC, Arcand J.
J Clin Hypertens (Greenwich). 2018 Nov 7. doi: 10.1111/jch.13408. [Epub ahead of print]
PMID: 30402970
Abstract
The purpose of this review was to identify, summarize, and critically appraise studies on dietary salt and health outcomes that were published from August 2016 to March 2017. The search strategy was adapted from a previous systematic review on dietary salt and health. Studies that meet standards for methodological quality criteria and eligible health outcomes are reported in detailed critical appraisals. Overall, 47 studies were identified and are summarized in this review. Two studies assessed all-cause or disease-specific mortality outcomes, eight studies assessed morbidity reduction-related outcomes, three studies assessed outcomes related to symptoms/quality of life/functional status, 25 studies assessed blood pressure (BP) outcomes and other clinically relevant surrogate outcomes, and nine studies assessed physiologic surrogate outcomes. Eight of these studies met the criteria for outcomes and methodological quality and underwent detailed critical appraisals and commentary. Five of these studies found adverse effects of salt intake on health outcomes (BP; death due to kidney disease and initiation of dialysis; total kidney volume and composite of kidney function; composite of cardiovascular disease (CVD) events including, and risk of mortality); one study reported the benefits of salt restriction in chronic BP and two studies reported neutral results (BP and risk of CKD). Overall, these articles confirm the negative effects of excessive sodium intake on health outcomes.

Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health.
Fontana L, Cummings NE, Arriola Apelo SI, Neuman JC, Kasza I, Schmidt BA, Cava E, Spelta F, Tosti V, Syed FA, Baar EL, Veronese N, Cottrell SE, Fenske RJ, Bertozzi B, Brar HK, Pietka T, Bullock AD, Figenshau RS, Andriole GL, Merrins MJ, Alexander CM, Kimple ME, Lamming DW.
Cell Rep. 2016 Jul 12;16(2):520-530. doi: 10.1016/j.celrep.2016.05.092. Epub 2016 Jun 23.
PMID: 27346343 Free PMC Article
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947548/
Abstract
Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet.

Reversing the immune ageing clock: lifestyle modifications and pharmacological interventions.
Duggal NA.
Biogerontology. 2018 Dec;19(6):481-496. doi: 10.1007/s10522-018-9771-7. Epub 2018 Sep 29. Review.
PMID: 30269199
https://sci-hub.tw/10.1007/s10522-018-9771-7
Abstract
It is widely accepted that ageing is accompanied by remodelling of the immune system, including reduced numbers of naïve T cells, increased senescent or exhausted T cells, compromise to monocyte, neutrophil and natural killer cell function and an increase in systemic inflammation. In combination these changes result in increased risk of infection, reduced immune memory, reduced immune tolerance and immune surveillance, with significant impacts upon health in old age. More recently it has become clear that the rate of decline in the immune system is malleable and can be influenced by environmental factors such as physical activity as well as pharmacological interventions. This review discusses briefly our current understanding of immunesenescence and then focuses on lifestyle interventions and therapeutic strategies that have been shown to restore immune functioning in aged individuals.
KEYWORDS:
Ageing; Immunesenescence; Inflammaging

[AlPater]

Salt and cardiovascular disease in PURE: A large sample size cannot make up for erroneous estimations.
Tan M, He FJ, MacGregor GA.
J Renin Angiotensin Aldosterone Syst. 2018 Oct-Dec;19(4):1470320318810015. doi: 10.1177/1470320318810015.
PMID: 30404579
https://journals.sagepub.com/doi/10.1177/1470320318810015
Abstract
The latest Prospective Urban Rural Epidemiology (PURE) study claims that salt reduction should be confined to settings where its intake exceeds 12.7 g/day and that eating less than 11.1 g/day of salt could increase cardiovascular risk. More specifically, Mente et al. suggested that (a) salt intake was positively associated with stroke only when it exceeded 12.7 g/day, (b) salt intake was inversely associated with myocardial infarction and total mortality, and (c) these associations were largely independent of blood pressure. These provocative findings challenge the robust evidence on the role of salt reduction in the prevention of cardiovascular disease and call into question the World Health Organization's global recommendation to reduce salt intake to less than 5 g/day. However, Mente et al.'s re-analysis of the PURE data has several severe methodological problems, including erroneous estimations of salt intake from a single spot urine using the problematic Kawasaki formula. As such, these implausible results cannot be used to refute the strong evidence supporting the benefits of salt reduction for the general population worldwide.
KEYWORDS:
Salt; cardiovascular disease; mortality; prevention; salt reduction programmes
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Urinary sodium excretion, blood pressure, cardiovascular disease, and mortality: a community-level prospective epidemiological cohort study.
Mente A, O'Donnell M, Rangarajan S, McQueen M, Dagenais G, Wielgosz A, Lear S, Ah STL, Wei L, Diaz R, Avezum A, Lopez-Jaramillo P, Lanas F, Mony P, Szuba A, Iqbal R, Yusuf R, Mohammadifard N, Khatib R, Yusoff K, Ismail N, Gulec S, Rosengren A, Yusufali A, Kruger L, Tsolekile LP, Chifamba J, Dans A, Alhabib KF, Yeates K, Teo K, Yusuf S.
Lancet. 2018 Aug 11;392(10146):496-506. doi: 10.1016/S0140-6736(18)31376-X. Epub 2018 Aug 9.
PMID: 30129465
https://sci-hub.tw/10.1016/S0140-6736(18)31376-X
Abstract
BACKGROUND:
WHO recommends that populations consume less than 2 g/day sodium as a preventive measure against cardiovascular disease, but this target has not been achieved in any country. This recommendation is primarily based on individual-level data from short-term trials of blood pressure (BP) without data relating low sodium intake to reduced cardiovascular events from randomised trials or observational studies. We investigated the associations between community-level mean sodium and potassium intake, cardiovascular disease, and mortality.
METHODS:
The Prospective Urban Rural Epidemiology study is ongoing in 21 countries. Here we report an analysis done in 18 countries with data on clinical outcomes. Eligible participants were adults aged 35-70 years without cardiovascular disease, sampled from the general population. We used morning fasting urine to estimate 24 h sodium and potassium excretion as a surrogate for intake. We assessed community-level associations between sodium and potassium intake and BP in 369 communities (all >50 participants) and cardiovascular disease and mortality in 255 communities (all >100 participants), and used individual-level data to adjust for known confounders.
FINDINGS:
95 767 participants in 369 communities were assessed for BP and 82 544 in 255 communities for cardiovascular outcomes with follow-up for a median of 8·1 years. 82 (80%) of 103 communities in China had a mean sodium intake greater than 5 g/day, whereas in other countries 224 (84%) of 266 communities had a mean intake of 3-5 g/day. Overall, mean systolic BP increased by 2·86 mm Hg per 1 g increase in mean sodium intake, but positive associations were only seen among the communities in the highest tertile of sodium intake (p<0·0001 for heterogeneity). The association between mean sodium intake and major cardiovascular events showed significant deviations from linearity (p=0·043) due to a significant inverse association in the lowest tertile of sodium intake (lowest tertile <4·43 g/day, mean intake 4·04 g/day, range 3·42-4·43; change -1·00 events per 1000 years, 95% CI -2·00 to -0·01, p=0·0497), no association in the middle tertile (middle tertile 4·43-5·08 g/day, mean intake 4·70 g/day, 4·44-5.05; change 0·24 events per 1000 years, -2·12 to 2·61, p=0·8391), and a positive but non-significant association in the highest tertile (highest tertile >5·08 g/day, mean intake 5·75 g/day, >5·08-7·49; change 0·37 events per 1000 years, -0·03 to 0·78, p=0·0712). A strong association was seen with stroke in China (mean sodium intake 5·58 g/day, 0·42 events per 1000 years, 95% CI 0·16 to 0·67, p=0·0020) compared with in other countries (4·49 g/day, -0·26 events, -0·46 to -0·06, p=0·0124; p<0·0001 for heterogeneity). All major cardiovascular outcomes decreased with increasing potassium intake in all countries.
INTERPRETATION:
Sodium intake was associated with cardiovascular disease and strokes only in communities where mean intake was greater than 5 g/day. A strategy of sodium reduction in these communities and countries but not in others might be appropriate.
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Salt and heart disease: a second round of "bad science"?
Messerli FH, Hofstetter L, Bangalore S.
Lancet. 2018 Aug 11;392(10146):456-458. doi: 10.1016/S0140-6736(18)31724-0. Epub 2018 Aug 9. No abstract available.
PMID: 30129446
https://sci-hub.tw/10.1016/S0140-6736(18)31724-0

A plant-based diet in overweight individuals in a 16-week randomized clinical trial: metabolic benefits of plant protein.
Kahleova H, Fleeman R, Hlozkova A, Holubkov R, Barnard ND.
Nutr Diabetes. 2018 Nov 2;8(1):58. doi: 10.1038/s41387-018-0067-4.
PMID: 30405108
Abstract
BACKGROUND AND OBJECTIVES:
A plant-based diet is an effective strategy in the treatment of obesity. In this 16-week randomized clinical trial, we tested the effect of a plant-based diet on body composition and insulin resistance. As a part of this trial, we investigated the role of plant protein on these outcomes.
SUBJECTS AND METHODS:
Overweight participants (n = 75) were randomized to follow a plant-based (n = 38) or a control diet (n = 37). Dual X-ray Absorptiometry assessed body composition, Homeostasis Model Assessment (HOMA-IR) assessed insulin resistance, and a linear regression model was used to test the relationship between protein intake, body composition, and insulin resistance.
RESULTS:
The plant-based vegan diet proved to be superior to the control diet in improving body weight, fat mass, and insulin resistance markers. Only the vegan group showed significant reductions in body weight (treatment effect -6.5 [95% CI -8.9 to -4.1] kg; Gxt, p < 0.001), fat mass (treatment effect -4.3 [95% CI -5.4 to -3.2] kg; Gxt, p < 0.001), and HOMA-IR (treatment effect -1.0 [95% CI -1.2 to -0.8]; Gxt, p = 0.004). The decrease in fat mass was associated with an increased intake of plant protein and decreased intake of animal protein (r = -0.30, p = 0.011; and r = +0.39, p = 0.001, respectively). In particular, decreased % leucine intake was associated with a decrease in fat mass (r = +0.40; p < 0.001), in both unadjusted and adjusted models for changes in BMI and energy intake. In addition, decreased % histidine intake was associated with a decrease in insulin resistance (r = +0.38; p = 0.003), also independent of changes in BMI and energy intake.
CONCLUSIONS:
These findings provide evidence that plant protein, as a part of a plant-based diet, and the resulting limitation of leucine and histidine intake are associated with improvements in body composition and reductions in both body weight and insulin resistance.

Dairy Consumption and Cardiometabolic Diseases: Systematic Review and Updated Meta-Analyses of Prospective Cohort Studies.
Soedamah-Muthu SS, de Goede J.
Curr Nutr Rep. 2018 Nov 8. doi: 10.1007/s13668-018-0253-y. [Epub ahead of print] Review.
PMID: 30406514
Abstract
PURPOSE OF REVIEW:
Dairy products contain both beneficial and harmful nutrients in relation to cardiometabolic diseases. Here, we provide the latest scientific evidence regarding the relationship between dairy products and cardiometabolic diseases by reviewing the literature and updating meta-analyses of observational studies.
RECENT FINDINGS:
We updated our previous meta-analyses of cohort studies on type 2 diabetes, coronary heart disease (CHD), and stroke with nine studies and confirmed previous results. Total dairy and low-fat dairy (per 200 g/d) were inversely associated with a 3-4% lower risk of diabetes. Yogurt was non-linearly inversely associated with diabetes (RR = 0.86, 95% CI: 0.83-0.90 at 80 g/d). Total dairy and milk were not associated with CHD (RR~1.0). An increment of 200 g of daily milk intake was associated with an 8% lower risk of stroke. The latest scientific evidence confirmed neutral or beneficial associations between dairy products and risk of cardiometabolic diseases.
KEYWORDS:
Cardiometabolic; Coronary heart disease; Dairy products; Stroke; Type 2 diabetes
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Associations of Calcium and Dairy Products with All-Cause and Cause-Specific Mortality in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Prospective Cohort Study.
Um CY, Judd SE, Flanders WD, Fedirko V, Bostick RM.
Nutr Cancer. 2017 Nov-Dec;69(8):1185-1195. doi: 10.1080/01635581.2017.1367946. Epub 2017 Nov 10.
PMID: 29125314
Abstract
Associations of calcium and dairy product intakes with cardiovascular disease risk and cancer mortality are controversial. We investigated associations of calcium and dairy product intakes with mortality in the prospective REasons for Geographic and Racial Differences in Stroke study (n = 30,239). Of 2,966 total deaths, 32.3% were from CVD and 28.8% from cancer. For those in the upper relative to the lowest quintile of intakes, from Cox proportional hazards regression models, the multivariable-adjusted hazard ratios (HRs) for all-cause mortality were 1.13 (95% confidence intervals [CI] 0.95-1.35; P-trend 0.004) for whole milk, and 0.75 (CI 0.61-0.93; P-trend 0.001) for nonfat milk; for CVD mortality the corresponding HRs were 0.80 (CI 0.55-1.16; P-trend 0.80) and 0.72 (CI 0.49-1.05; P-trend 0.06); and for cancer mortality they were 1.56 (CI 1.17-2.08; P-trend 0.006) and 0.89 (CI 0.62-1.28; P-trend 0.86). Calcium (total, dietary, supplemental) and total dairy product intakes were not associated with all-cause, cardiovascular, or cancer mortality. These results suggest that whole milk consumption may be directly associated with cancer mortality; non-fat milk consumption may be inversely associated with all-cause and cardiovascular- and cancer-specific mortality; and calcium intake independent of milk product intakes may not be associated with mortality.

Television viewing time, walking time, and risk of type 2 diabetes in Japanese men and women: The Japan Collaborative Cohort Study.
Ikehara S, Iso H, Maruyama K, Ukawa S, Tamakoshi A; Japan Collaborative Cohort Study.
Prev Med. 2018 Nov 5. pii: S0091-7435(18)30351-7. doi: 10.1016/j.ypmed.2018.11.006. [Epub ahead of print]
PMID: 30408447
Abstract
We examined the effect of television viewing and walking on the risk of type 2 diabetes among an Asian population. A total of 25,240 participants (9786 men and 15,454 women) aged 40-79 years, with no history of diabetes, stroke, coronary heart disease, or cancer at the baseline (1988-1990) and who have completed the 5-year follow-up questionnaire were included. During the 5-year follow-up, 778 new cases of type 2 diabetes were reported (397 men and 381 women). Television viewing time was positively associated with risk of type 2 diabetes (p for trend = 0.01). The multivariable OR (95% CI) for ≥5 h/day versus <2 h/day television viewing was 1.51 (1.03-2.19) in women and 1.06 (0.71-1.59) in men (p for interaction = 0.82). Walking time was inversely associated with type 2 diabetes risk in a fully adjusted model (p for trend = 0.02). The multivariable OR for type 2 diabetes of ≥1 h/day walking time was 0.87 (0.71-1.06) compared with 0.5 h/day walking time. The inverse association was found in men (p for trend = 0.02), but not in women (p for trend = 0.38) (p for interaction = 0.36). The multivariable OR for type 2 diabetes of <5 h/day television viewing and ≥1 h/day walking times was 0.72 (0.55-0.94) in fully adjusted model compared with ≥5 h/day television viewing and <1 h/day walking times. Limiting television viewing time and increasing walking time may reduce risk of type 2 diabetes among Japanese.
KEYWORDS: 
Prospective study; Television viewing; Type 2 diabetes mellitus; Walking

Effect of low carbohydrate high fat diet on LDL cholesterol and gene expression in normal-weight, young adults: A randomized controlled study.
Retterstøl K, Svendsen M, Narverud I, Holven KB.
Atherosclerosis. 2018 Oct 17;279:52-61. doi: 10.1016/j.atherosclerosis.2018.10.013. [Epub ahead of print]
PMID: 30408717
Abstract
BACKGROUND AND AIMS:
The effects of a low carbohydrate/high fat (LCHF) diet on health are debated. This study aims to explore the effects of a diet with less than 20 g carbohydrates per day (LCHF) on plasma low density lipoprotein cholesterol (LDL-C) in young and healthy adults. The secondary aim is the assessment of lipid profile and peripheral blood mononuclear cells (PBMC) gene expression.
METHODS:
This was a randomized controlled parallel-designed intervention study. Participants were either assigned to a three-week LCHF diet or a control group continuing habitual diet ad libitum, in both groups.
RESULTS:
In total, 30 healthy normal weight participants completed the study. Nine subjects did not complete it due to adverse events or withdrawn consent. In the LCHF diet group (n = 15), plasma LDL-C increased from (mean ± SD) 2.2 ± 0.4 mmol/l before intervention to 3.1 ± 0.8 after, while in the control group (n = 15), LDL-C remained unchanged: 2.5 ± 0.8 mmol/l (p < 0.001 between groups). There was a significant increase in apolipoprotein B, total cholesterol, high-density lipoprotein cholesterol, free fatty acids, uric acid and urea in the LCHF group versus controls. Plasma levels of triglycerides, lipoprotein (a), glucose, C-peptide or C-reactive protein (CRP), blood pressure, body weight or body composition did not differ between the groups. PBMC gene expression of sterol regulator element binding protein 1 (SREBP-1) was increased in the LCHF group versus controls (p ≤ 0.01). The individual increase in LDL-C from baseline varied between 5 and 107% in the LCHF group.
CONCLUSIONS:
An LCHF diet for three weeks increased LDL-C with 44% versus controls. The individual response on LCHF varied profoundly.

[AlPater]

Fructose increases risk for kidney stones: potential role in metabolic syndrome and heat stress.
Johnson RJ, Perez-Pozo SE, Lillo JL, Grases F, Schold JD, Kuwabara M, Sato Y, Hernando AA, Garcia G, Jensen T, Rivard C, Sanchez-Lozada LG, Roncal C, Lanaspa MA.
BMC Nephrol. 2018 Nov 8;19(1):315. doi: 10.1186/s12882-018-1105-0.
PMID: 30409184
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-018-1105-0
Abstract
BACKGROUND:
Fructose intake, mainly as table sugar or high fructose corn syrup, has increased in recent decades and is associated with increased risk for kidney stones. We hypothesized that fructose intake alters serum and urinary components involved in stone formation.
METHODS:
We analyzed a previously published randomized controlled study that included 33 healthy male adults (40-65 years of age) who ingested 200 g of fructose (supplied in a 2-L volume of 10% fructose in water) daily for 2 weeks. Participants were evaluated at the Unit of Nephrology of the Mateo Orfila Hospital in Menorca. Changes in serum levels of magnesium, calcium, uric acid, phosphorus, vitamin D, and intact PTH levels were evaluated. Urine magnesium, calcium, uric acid, phosphorus, citrate, oxalate, sodium, potassium, as well as urinary pH, were measured.
RESULTS:
Ingestion of fructose was associated with an increased serum level of uric acid (p < 0.001), a decrease in serum ionized calcium (p = 0.003) with a mild increase in PTH (p < 0.05) and a drop in urinary pH (p = 0.02), an increase in urine oxalate (p = 0.016) and decrease in urinary magnesium (p = 0.003).
CONCLUSIONS:
Fructose appears to increase urinary stone formation in part via effects on urate metabolism and urinary pH, and also via effects on oxalate. Fructose may be a contributing factor for the development of kidney stones in subjects with metabolic syndrome and those suffering from heat stress.
KEYWORDS:
Citrate; Fructose; Kidney stone; Magnesium; Oxalate; Sucrose; Sugar; Uric acid

Whole grain diet reduces systemic inflammation: A meta-analysis of 9 randomized trials.
Xu Y, Wan Q, Feng J, Du L, Li K, Zhou Y.
Medicine (Baltimore). 2018 Oct;97(43):e12995. doi: 10.1097/MD.0000000000012995.
PMID: 30412134
Abstract
BACKGROUNDS:
Observational studies had suggested an inverse association between whole grain consumption and concentration of inflammatory markers, but evidence from interventional studies was inconsistent. Therefore, we conducted a meta-analysis of randomized trials to have a better understanding of this issue.
METHODS:
This study has been registered in PROSPERO (ID: CRD42018096533). We searched PubMed, Web of Science, Embase, Medline, and Cochrane Library for articles focusing on the topic from inception to 1 January, 2018. Summary standardized mean difference (SMD) and 95% confidence interval (CI) were calculated by using either random effect model or fixed effect model according to the heterogeneity of included studies. Subgroup analysis was also performed.
RESULTS:
Totally 9 randomized trials included 838 participants were identified. In a pooled analysis of all studies, consumption of whole grains had an inverse association with inflammatory markers (SMD 0.16, 95% CI, 0.02-0.30), including C-reactive protein (CRP), Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β). Specific analyses for CRP and IL-6 yielded that whole grain diet was related with a significant decrease in the concentration of CRP (SMD 0.29, 95% CI, 0.08-0.50) and IL-6 (SMD 0.19, 95% CI, 0.03-0.36).
CONCLUSIONS:
The evidence suggested that citizens could benefit from increased whole grain intake for reducing systemic inflammation. Further well-designed studies are required to investigate the mechanism under the appearance.

[AlPater]

The effect of drinking water pH on the human gut microbiota and glucose regulation: results of a randomized controlled cross-over intervention.
Hansen TH, Thomassen MT, Madsen ML, Kern T, Bak EG, Kashani A, Allin KH, Hansen T, Pedersen O.
Sci Rep. 2018 Nov 9;8(1):16626. doi: 10.1038/s41598-018-34761-5.
PMID: 30413727
Abstract
Studies in rodent models have shown that alterations in drinking water pH affect both the composition of the gut microbiota and host glucose regulation. To explore a potential impact of electrochemically reduced alkaline (pH ≈ 9) versus neutral (pH ≈ 7) drinking water (2 L/day) on human intestinal microbiota and host glucose metabolism we conducted a randomized, non-blinded, cross-over study (two 2-week intervention periods, separated by a 3-week wash-out) in 29 healthy, non-smoking Danish men, aged 18 to 35 years, with a body mass index between 20.0 to 27.0 kg m-2. Volunteers were ineligible if they had previously had abdominal surgery, had not been weight stabile for at least two months, had received antibiotic treatment within 2 months, or had a habitual consumption of caloric or artificially sweetened beverages in excess of 1 L/week or an average intake of alcohol in excess of 7 units/week. Microbial DNA was extracted from faecal samples collected at four time points, before and after each intervention, and subjected to 16S rRNA gene amplicon sequencing (Illumina MiSeq, V4 region). Glycaemic regulation was evaluated by means of an oral glucose tolerance test.No differential effect of alkaline versus neutral drinking water was observed for the primary outcome, overall gut microbiota diversity as represented by Shannon's index. Similarly, neither a differential effect on microbiota richness or community structure was observed. Nor did we observe a differential effect on the abundance of individual operational taxonomic units (OTUs) or genera. However, analyses of within period effects revealed a significant (false discovery rate ≤5%) increase in the relative abundance of 9 OTUs assigned to order Clostridiales, family Ruminococcaceae, genus Bacteroides, and species Prevotella copri, indicating a potential effect of quantitative or qualitative changes in habitual drinking habits. An increase in the concentration of plasma glucose at 30 minutes and the incremental area under the curve of plasma glucose from 0 30 and 0 120 minutes, respectively, was observed when comparing the alkaline to the neutral intervention. However, results did not withstand correction for multiplicity. In contrast to what has been reported in rodents, a change in drinking water pH had no impact on the composition of the gut microbiota or glucose regulation in young male adults.

Dietary branched-chain amino acids intake exhibited a different relationship with type 2 diabetes and obesity risk: a meta-analysis.
Okekunle AP, Zhang M, Wang Z, Onwuka JU, Wu X, Feng R, Li C.
Acta Diabetol. 2018 Nov 9. doi: 10.1007/s00592-018-1243-7. [Epub ahead of print]
PMID: 30413881
Abstract
AIM:
To assess whether oral branched-chain amino acids (BCAA) supplementation exerts influence on circulating BCAA and the significance of dietary BCAA in type 2 diabetes and obesity risk.
METHOD:
We searched PUBMED, EMBASE and Cochrane library through June 2018 to retrieve and screen published reports for inclusion in the meta-analysis after methodological assessment. Heterogeneity of studies was evaluated using I2 statistics, while sensitivity analysis and funnel plot were used to evaluate the potential effect of individual studies on the overall estimates and publication bias, respectively, using RevMan 5.3.
RESULT:
Eight articles on randomized clinical trial of oral BCAA supplementation, and seven articles on dietary BCAA intake and type 2 diabetes/obesity risks were eligible for inclusion in our meta-analyses. Mean difference and 95% confidence interval (CI) of circulating leucine was 39.65 (3.54, 75.76) µmol/L, P = 0.03 post-BCAA supplementation. Also, OR and 95% CI for higher total BCAA intake and metabolic disorder risks were, 1.32 (1.14, 1.53), P = 0.0003-type 2 diabetes and 0.62 (0.47, 0.82), P = 0.0008-obesity.
CONCLUSION:
Oral BCAA supplementation exerts modest influence on circulating leucine profile and higher total BCAA intake is positively and contra-positively associated with type 2 diabetes and obesity risk, respectively.
KEYWORDS:
Branched-chain amino acids; Meta-analysis; Obesity; Type 2 diabetes

[AlPater]

Fish Oil Supplementation in Pregnancy Increases Gestational Age, Size for Gestational Age, and Birth Weight in Infants: A Randomized Controlled Trial.
Vinding RK, Stokholm J, Sevelsted A, Chawes BL, Bønnelykke K, Barman M, Jacobsson B, Bisgaard H.
J Nutr. 2018 Nov 9. doi: 10.1093/jn/nxy204. [Epub ahead of print]
PMID: 30418579
Abstract
BACKGROUND:
Randomized trials have reported that supplementation with n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in pregnancy can prolong pregnancy and thereby increase birth weight.
OBJECTIVE:
We aimed to examine the relations of n-3 LCPUFA supplementation in pregnancy with duration of pregnancy, birth weight, and size for gestational age (GA).
METHODS:
This was a double-blind randomized controlled trial conducted in 736 pregnant women and their offspring, from the Copenhagen Prospective Studies on Asthma in Childhood2010cohort. They were recruited between weeks 22 and 26 in pregnancy and randomly assigned to either of 2.4 g n-3 LCPUFA or control (olive oil) daily until 1 wk after birth. Exclusion criteria were endocrine, cardiovascular, or nephrologic disorders and vitamin D supplementation intake >600 IU/d. In this study we analyzed secondary outcomes, and further excluded twin pregnancies and extrauterine death. The primary outcome for the trial was persistent wheeze or asthma.
RESULTS:
The random assignment ran between 2008 and 2010. Six hundred and ninety-nine mother-infant pairs were included in the analysis. n-3 LCPUFA compared with control was associated with a 2-d prolongation of pregnancy [median (IQR): 282 (275-288) d compared with 280 (273-286) d, P = 0.02], a 97-g higher birth weight (mean ± SD: 3601 ± 534 g compared with 3504 ± 528 g, P = 0.02), and an increased size for GA according to the Norwegian population-based growth curves-Skjærven (mean ± SD: 49.9 ± 28.3 percentiles compared with 44.5 ± 27.6 percentiles, P = 0.01).
CONCLUSION:
Supplementing pregnant women with n-3 LCPUFAs during the third trimester is associated with prolonged gestation and increased size for GA, leading to a higher birth weight in this randomized controlled trial.

Vitamin D lowers risk of cancer death, fish oil reduces odds of heart attack, study shows
New VITAL study is the first large test of both supplements in the general population
Thomson Reuters · Posted: Nov 12, 2018
https://www.cbc.ca/news/health/large-u-s-study-vitamin-d-fish-oil-supplements-1.4901933
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Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer.
Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, Gibson H, Albert CM, Gordon D, Copeland T, D'Agostino D, Friedenberg G, Ridge C, Bubes V, Giovannucci EL, Willett WC, Buring JE; VITAL Research Group.
N Engl J Med. 2018 Nov 10. doi: 10.1056/NEJMoa1811403. [Epub ahead of print]
PMID: 30415637
https://www.nejm.org/doi/full/10.1056/NEJMoa1811403
Abstract
BACKGROUND
Higher intake of marine n−3 (also called omega-3) fatty acids has been associated with reduced risks of cardiovascular disease and cancer in several observational studies. Whether supplementation with n−3 fatty acids has such effects in general populations at usual risk for these end points is unclear.
METHODS
We conducted a randomized, placebo-controlled trial, with a two-by-two factorial design, of vitamin D3 (at a dose of 2000 IU per day) and marine n−3 fatty acids (at a dose of 1 g per day) in the primary prevention of cardiovascular disease and cancer among men 50 years of age or older and women 55 years of age or older in the United States. Primary end points were major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes) and invasive cancer of any type. Secondary end points included individual components of the composite cardiovascular end point, the composite end point plus coronary revascularization (expanded composite of cardiovascular events), site-specific cancers, and death from cancer. Safety was also assessed. This article reports the results of the comparison of n−3 fatty acids with placebo.
RESULTS
A total of 25,871 participants, including 5106 black participants, underwent randomization. During a median follow-up of 5.3 years, a major cardiovascular event occurred in 386 participants in the n−3 group and in 419 in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P=0.24). Invasive cancer was diagnosed in 820 participants in the n−3 group and in 797 in the placebo group (hazard ratio, 1.03; 95% CI, 0.93 to 1.13; P=0.56). In the analyses of key secondary end points, the hazard ratios were as follows: for the expanded composite end point of cardiovascular events, 0.93 (95% CI, 0.82 to 1.04); for total myocardial infarction, 0.72 (95% CI, 0.59 to 0.90); for total stroke, 1.04 (95% CI, 0.83 to 1.31); for death from cardiovascular causes, 0.96 (95% CI, 0.76 to 1.21); and for death from cancer (341 deaths from cancer), 0.97 (95% CI, 0.79 to 1.20). In the analysis of death from any cause (978 deaths overall), the hazard ratio was 1.02 (95% CI, 0.90 to 1.15). No excess risks of bleeding or other serious adverse events were observed.
CONCLUSIONS
Supplementation with n−3 fatty acids did not result in a lower incidence of major cardiovascular events or cancer than placebo. 
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Keaney John F., Rosen Clifford J.. (2018) VITAL Signs for Dietary Supplementation to Prevent Cancer and Heart Disease. N Engl J Med DOI: 10.1056/NEJMe1814933. 
Free Full Text
https://www.nejm.org/doi/full/10.1056/NEJMe1814933
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Manson JoAnn E., Cook Nancy R., Lee I-Min, Christen William, Bassuk Shari S., Mora Samia, Gibson Heike, Gordon David, Copeland Trisha, D’Agostino Denise, Friedenberg Georgina, Ridge Claire, Bubes Vadim, Giovannucci Edward L., Willett Walter C., Buring Julie E.. (2018) 
Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med DOI: 10.1056/NEJMoa1809944. 
Free Full Text
https://www.nejm.org/doi/pdf/10.1056/NEJMoa1809944
Abstract
BACKGROUND
It is unclear whether supplementation with vitamin D reduces the risk of cancer or cardiovascular disease, and data from randomized trials are limited.
METHODS
We conducted a nationwide, randomized, placebo-controlled trial, with a two-by-two factorial design, of vitamin D3 (cholecalciferol) at a dose of 2000 IU per day and marine n−3 (also called omega-3) fatty acids at a dose of 1 g per day for the prevention of cancer and cardiovascular disease among men 50 years of age or older and women 55 years of age or older in the United States. Primary end points were invasive cancer of any type and major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes). Secondary end points included site-specific cancers, death from cancer, and additional cardiovascular events. This article reports the results of the comparison of vitamin D with placebo.
RESULTS
A total of 25,871 participants, including 5106 black participants, underwent randomization. Supplementation with vitamin D was not associated with a lower risk of either of the primary end points. During a median follow-up of 5.3 years, cancer was diagnosed in 1617 participants (793 in the vitamin D group and 824 in the placebo group; hazard ratio, 0.96; 95% confidence interval [CI], 0.88 to 1.06; P=0.47). A major cardiovascular event occurred in 805 participants (396 in the vitamin D group and 409 in the placebo group; hazard ratio, 0.97; 95% CI, 0.85 to 1.12; P=0.69). In the analyses of secondary end points, the hazard ratios were as follows: for death from cancer (341 deaths), 0.83 (95% CI, 0.67 to 1.02); for breast cancer, 1.02 (95% CI, 0.79 to 1.31); for prostate cancer, 0.88 (95% CI, 0.72 to 1.07); for colorectal cancer, 1.09 (95% CI, 0.73 to 1.62); for the expanded composite end point of major cardiovascular events plus coronary revascularization, 0.96 (95% CI, 0.86 to 1.08); for myocardial infarction, 0.96 (95% CI, 0.78 to 1.19); for stroke, 0.95 (95% CI, 0.76 to 1.20); and for death from cardiovascular causes, 1.11 (95% CI, 0.88 to 1.40). In the analysis of death from any cause (978 deaths), the hazard ratio was 0.99 (95% CI, 0.87 to 1.12). No excess risks of hypercalcemia or other adverse events were identified.
CONCLUSIONS
Supplementation with vitamin D did not result in a lower incidence of invasive cancer or cardiovascular events than placebo.