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

[AlPater]

Central IGF-1 protects against features of cognitive and sensorimotor decline with aging in male mice.
Farias Quipildor GE, Mao K, Hu Z, Novaj A, Cui MH, Gulinello M, Branch CA, Gubbi S, Patel K, Moellering DR, Tarantini S, Kiss T, Yabluchanskiy A, Ungvari Z, Sonntag WE, Huffman DM.
Geroscience. 2019 May 10. doi: 10.1007/s11357-019-00065-3. [Epub ahead of print]
PMID: 31076997
https://sci-hub.tw/https://link.springer.com/article/10.1007/s11357-019-00065-3
Abstract
Disruptions in growth hormone/insulin-like growth factor-1 (GH/IGF-1) signaling have been linked to improved longevity in mice and humans. Nevertheless, while IGF-1 levels are associated with increased cancer risk, they have been paradoxically implicated with protection from other age-related conditions, particularly in the brain, suggesting that strategies aimed at selectively increasing central IGF-1 action may have favorable effects on aging. To test this hypothesis, we generated inducible, brain-specific (TRE-IGF-1 × Camk2a-tTA) IGF-1 (bIGF-1) overexpression mice and studied effects on healthspan. Doxycycline was removed from the diet at 12 weeks old to permit post-development brain IGF-1 overexpression, and animals were monitored up to 24 months. Brain IGF-1 levels were increased approximately twofold in bIGF-1 mice, along with greater brain weights, volume, and myelin density (P < 0.05). Age-related changes in rotarod performance, exercise capacity, depressive-like behavior, and hippocampal gliosis were all attenuated specifically in bIGF-1 male mice (P < 0.05). However, chronic brain IGF-1 failed to prevent declines in cognitive function or neurovascular coupling. Therefore, we performed a short-term intranasal (IN) treatment of either IGF-1 or saline in 24-month-old male C57BL/6 mice and found that IN IGF-1 treatment tended to reduce depressive (P = 0.09) and anxiety-like behavior (P = 0.08) and improve motor coordination (P = 0.07) and unlike transgenic mice improved motor learning (P < 0.05) and visuospatial and working memory (P < 0.05). These data highlight important sex differences in how brain IGF-1 action impacts healthspan and suggest that translational approaches that target IGF-1 centrally can restore cognitive function, a possibility that should be explored as a strategy to combat age-related cognitive decline.
KEYWORDS:
Aging; Brain; Cognitive and sensorimotor decline; Cognitive function; Healthspan; IGF-1; Intransasal

Impact of whole egg intake on blood pressure, lipids and lipoproteins in middle-aged and older population: A systematic review and meta-analysis of randomized controlled trials.
Wang MX, Wong CH, Kim JE.
Nutr Metab Cardiovasc Dis. 2019 Apr 20. pii: S0939-4753(19)30118-8. doi: 10.1016/j.numecd.2019.04.004. [Epub ahead of print]
PMID: 31076323
https://sci-hub.tw/10.1016/j.numecd.2019.04.004
Abstract
BACKGROUND AND AIM:
Effects of whole egg consumption on cardiovascular diseases (CVD) risk in the middle-aged and older population remain unclear due to inconsistent findings from observational and randomized controlled trials (RCTs). This meta-analysis aimed to assess the impacts of whole egg and egg category (whole eggs versus egg substitutes) intake quantity on CVD risk factors from systematically searched RCTs. Egg substitutes were hypothesized to have minimal effects of the blood lipid and lipoprotein profile as they are void of dietary cholesterol.
METHODS AND RESULTS:
As many as 434 studies identified from PubMed, Cochrane Library, CINAHL and Medline (Ovid) databases were screened and data were extracted from 8 selected RCTs. Quality of the selected studies were assessed and the overall effect sizes of weighted mean differences (WMD) were calculated using a random effects model. Non-differential effects in blood pressures, lipids and lipoproteins were observed when >4 whole eggs/week compared to ≤4 whole eggs/week were consumed. Intake of >4 whole eggs/week compared to equivalent amounts of egg substitutes caused greater elevations in blood total cholesterol (WMD: 0.198 mmol/L; 95% CIs: 0.056, 0.339), HDL cholesterol (WMD: 0.068 mmol/L; 95% CIs: 0.006, 0.130) and LDL cholesterol (WMD: 0.171 mmol/L; 95% CIs: 0.028, 0.315) but did not differentially affect triglycerides concentration.
CONCLUSION:
Overall, the results support the notion that quantity of whole egg intake does not affect CVD risk factors and consuming egg substitutes may also be beneficial compared to whole eggs on lowering CVD risk in the middle-aged and older population.
Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
KEYWORDS:
Blood lipids and lipoproteins; Blood pressure; Cardiovascular disease; Dietary cholesterol; Egg category; Middle-aged and older adults; Whole eggs

[AlPater]

Dietary Soy Intake Is Inversely Associated with Risk of Type 2 Diabetes in Japanese Women but Not in Men.
Konishi K, Wada K, Yamakawa M, Goto Y, Mizuta F, Koda S, Uji T, Tsuji M, Nagata C.
J Nutr. 2019 May 11. pii: nxz047. doi: 10.1093/jn/nxz047. [Epub ahead of print]
PMID: 31079144
Abstract
BACKGROUND:
Whole soy foods, as well as their components, including protein and isoflavones, have garnered attention because they may have beneficial effects against diabetes.
OBJECTIVES:
We examined associations between the intake of soy foods, soy protein, and soy isoflavones and the risk of diabetes in the Japanese population.
METHODS:
This prospective cohort study included 13,521 residents (5883 men and 7638 women; 35-69 y old) of Takayama City, Japan. The subjects responded to a self-administered baseline questionnaire in 1992 and to a follow-up questionnaire seeking information about diabetes in 2002. Their mean ± SD body mass index was 22.6 ± 2.6 kg/m2 (men) and 22.1 ± 2.7 (women). The intakes of total soy foods, fried soy foods, nonfried soy foods, soy protein, and soy isoflavones were estimated through the use of a validated food-frequency questionnaire administered in 1992. Associations between soy intake and the risk of diabetes were evaluated through the use of Cox proportional hazards models incorporating age, education level, physical activity, smoking status, alcohol consumption, history of hypertension, use of vitamin supplements, menopausal status, and dietary factors including glycemic load, total energy, total fat, meat, fruit, vegetables, and coffee.
RESULTS:
During a 10-y follow-up, 438 participants reported physician-diagnosed diabetes. Women in the highest tertile of intakes of total soy foods, fried soy foods, nonfried soy foods, soy protein, and soy isoflavone had significantly lower HRs, after controlling for covariates, than those with the lowest intakes. For example, HRs were 0.45 (95% CI: 0.30, 0.68; P-trend <0.001) for total soy food intake. In men, there were no significant associations between soy intake and the risk of diabetes.
CONCLUSIONS:
These results suggest that a high soy intake may be associated with a lower risk of diabetes in Japanese women.
KEYWORDS:
diabetes; diet; isoflavone; prospective studies; soy; the Japanese

Dietary Protein Intake and Falls in Older People: Longitudinal Analyses From the Osteoarthritis Initiative.
Veronese N, Soysal P, Stubbs B, Maggi S, Jackson SE, Demurtas J, Celotto S, Koyanagi A, Bolzetta F, Smith L.
J Am Med Dir Assoc. 2019 May 8. pii: S1525-8610(19)30301-9. doi: 10.1016/j.jamda.2019.03.014. [Epub ahead of print]
PMID: 31078488
Abstract
OBJECTIVES:
Literature regarding dietary protein intake and risk of falls is limited to a few studies with relatively small sample sizes and short follow-ups, which have reported contrasting findings. Thus, we investigated whether dietary protein intake is associated with risk of falls in a large cohort of North American adults.
DESIGN:
Data were drawn from the Osteoarthritis Initiative, a cohort study, with 8 years of follow-up.
SETTING AND PARTICIPANTS:
Community-dwelling adults with knee osteoarthritis or at high risk for this condition.
METHODS:
Dietary protein intake was recorded using the Block Brief 2000 food frequency questionnaire and categorized using gender-specific quartiles (Q). Falls were self-reported in response to the question "Did you fall during the past year?" categorized as yes vs no and made during the 6 visits over 8 years of follow-up. Results are reported as relative risks (RRs), with their 95% confidence intervals (CIs), using a multivariable Poisson regression.
RESULTS:
The final sample consisted of 4450 adults (mean age 61.2 years, females = 59.6%). Higher dietary protein intake was significantly associated with higher frequency of falls during the year before baseline. After adjusting for 17 potential confounders, people with the greatest amount of protein intake (Q4) had a significantly higher risk of falling over the 8-year follow-up period (RR 1.112, 95% CI 1.027-1.211, P = .009) than those with the lowest protein intake (Q1).
CONCLUSIONS/IMPLICATIONS:
In this cohort of people affected by knee osteoarthritis or at high risk for this condition, high dietary protein intake may increase the risk of falls in older people, but further research is needed to confirm or refute these findings.
KEYWORDS:
Falls; Osteoarthritis Initiative; aged; protein

[AlPater]

Addition of oat bran reduces HDL-C and does not potentialize effect of a low-calorie diet on remission of metabolic syndrome: A pragmatic, randomized, controlled, open-label nutritional trial.
Leão LSCS, Aquino LA, Dias JF, Koifman RJ.
Nutrition. 2019 Mar 23;65:126-130. doi: 10.1016/j.nut.2019.03.007. [Epub ahead of print]
PMID: 31082790
Abstract
OBJECTIVES:
It is unclear whether addition of soluble fiber to a low-calorie diet potentializes weight loss and amelioration of metabolic syndrome (MetS). The aim of this study was to analyze the effects of oat bran on prevalence of MetS and associated disorders.
METHODS:
A pragmatic, randomized controlled, 6-wk nutritional trial was carried out with 154 outpatients (mean age 47.6 ± 12.6 y of age). The intervention group (n = 83) received a low-calorie diet plus 40 g/d of oat bran; the control group (n = 71) received a low-calorie diet only. MetS parameters and prevalence were calculated and compared (using two-tailed statistical tests) before and after follow-up.
RESULTS:
After follow-up, a significant but similar reduction was observed in MetS prevalence (40% reduction, 63% and 64.8% prevalence in intervention and control groups, respectively; P = 0.226), body mass index, body weight, waist circumference, systolic and diastolic blood pressures, triacylglycerides, and blood glucose levels in both groups (P < 0.05). Mean high-density lipoprotein cholesterol (HDL-C) was reduced in the intervention group (43.6 ± 9.6 to 41.2 ± 9.5 mg/dL; P = 0.025), but not in the control group (44.6 ± 10.5 to 44.5 ± 12.1 mg/dL; P = 0.890). There was no significant difference in any of the variables between the groups, although the P-value for HDL-C was almost significant (P = 0.078). Calorie and dietetic fiber intake during the 6-wk period were similar in both groups.
CONCLUSIONS:
Daily consumption of oat bran did not potentialize the beneficial effects of a traditional low-calorie diet on the prevalence of MetS and associated disorders. Additionally, it reduced HDL-C.
KEYWORDS:
High-density lipoprotein cholesterol; Metabolic parameters; Metabolic syndrome; Oat bran; Randomized clinical trial; Soluble fiber

[AlPater]

Circulating Selenium Concentration Is Inversely Associated With the Prevalence of Stroke: Results From the Canadian Health Measures Survey and the National Health and Nutrition Examination Survey.
Hu XF, Stranges S, Chan LHM.
J Am Heart Assoc. 2019 May 21;8(10):e012290. doi: 10.1161/JAHA.119.012290.
PMID: 31084244
https://www.ahajournals.org/doi/pdf/10.1161/JAHA.119.012290
Abstract
Background Observational studies have suggested that selenium (Se) may have beneficial effects against certain cardiovascular outcomes, with a possible U-shaped association. We assessed the hypothesis that blood Se concentration might be inversely associated with the prevalence of stroke and the relationship would be nonlinear. Methods and Results Data collected from adult participants (aged ≥20 years) in the Canadian Health Measures Survey ( CHMS 2007-2011, n=7065) and the US National Health and Nutrition Examination Survey ( NHANES 2011-2012, n=5030) were analyzed. A total of 82 (1.16%) and 202 (4.02%) stroke cases were identified in CHMS and NHANES . Respondents with stroke had lower Se levels than those without stroke, with a mean difference of 16 μg/L and 12 μg/L for CHMS and NHANES , respectively. Respondents with high blood Se concentration (tertile 3) had a lower prevalence of stroke compared with those with low Se concentration (tertile 1). The adjusted odds ratios were 0.38 (95% CI : 0.15, 0.92) and 0.57 (95% CI : 0.31, 1.03) for CHMS and NHANES , respectively. A continuous decreasing trend of stroke with whole blood selenium was observed in CHMS , whereas the curve plateaued starting at 190 μg/L for NHANES , based on the cubic restricted spline regression. Sensitivity analysis using the serum and urinary Se concentrations demonstrates that our results were consistent across different selenium biomarkers. Conclusions We observed inverse cross-sectional associations between whole blood Se and the prevalence of stroke in representative samples of the Canadian and the US population.
KEYWORDS:
Canadian Health Measures Survey; National Health and Nutrition Examination Survey; diet; environment; selenium; stroke

Fluid Intake and Dietary Factors and the Risk of Incident Kidney Stones in UK Biobank: A Population-based Prospective Cohort Study.
Littlejohns TJ, Neal NL, Bradbury KE, Heers H, Allen NE, Turney BW.
Eur Urol Focus. 2019 May 10. pii: S2405-4569(19)30137-3. doi: 10.1016/j.euf.2019.05.002. [Epub ahead of print]
PMID: 31085062
Abstract
BACKGROUND:
Fluid intake and diet are thought to influence kidney stone risk. However, prospective studies have been limited to small samples sizes and/or restricted measures.
OBJECTIVE:
To investigate whether fluid intake and dietary factors are associated with the risk of developing a first kidney stone.
DESIGN, SETTING, AND PARTICIPANTS:
Participants were selected from UK Biobank, a population-based prospective cohort study.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
Cox proportional hazards models were used to investigate the association between fluid intake and dietary factors and the risk of a first incident kidney stone, ascertained from hospital inpatient records.
RESULTS AND LIMITATIONS:
After exclusion, 439 072 participants were available for the analysis, of whom 2057 had hospital admission with an incident kidney stone over a mean of 6.1 yr of follow-up. For every additional drink (200 ml) consumed per day of total fluid, the risk of kidney stones declined by 13% (hazard ratio {HR} = 0.87, 95% confidence interval [CI] 0.85-0.89). Similar patterns of associations were observed for tea, coffee, and alcohol, although no association was observed for water intake. Fruit and fibre intake was also associated with a lower risk (HR per 100 g increase of fruits per day = 0.88, 95% CI 0.83-0.93, and HR per 10 g fibre per day = 0.82, 95% CI 0.77-0.87), whereas meat and salt intake was associated with a higher risk (HR per 50 g increase in meat per week = 1.17, 95% CI 1.05-1.29, and HR for always vs never/rarely added salt to food = 1.33, 95% CI 1.12-1.58). Vegetable, fish, and cheese intake was not associated with kidney stone risk.
CONCLUSIONS:
The finding that high intake of total fluid, fruit, and fibre was associated with a lower risk of hospitalisation for a first kidney stone suggests that modifiable dietary factors could be targeted to prevent kidney stone development.
PATIENT SUMMARY:
We found that higher intake of total fluid, specifically tea, coffee, and alcohol (but not water), and consumption of fruit and foods high in fibre are linked with a reduced likelihood of developing kidney stones.
KEYWORDS:
Diet; Fluid; Kidney stones; Longitudinal; UK Biobank

The Impact of Retirement on Cardiovascular Disease and Its Risk Factors: A Systematic Review of Longitudinal Studies.
Xue B, Head J, McMunn A, Heyn PC.
Gerontologist. 2019 May 15. pii: gnz062. doi: 10.1093/geront/gnz062. [Epub ahead of print]
PMID: 31091304
https://academic.oup.com/gerontologist/advance-article/doi/10.1093/geront/gnz062/5489765
Abstract
BACKGROUND AND OBJECTIVES:
People are now spending longer in retirement than ever before and retirement has been found to influence health. This study systematically reviewed the impact of retirement on cardiovascular disease (CVD) and its risk factors (metabolic risk factors, blood biomarkers, physical activity, smoking, drinking, and diet).
RESEARCH DESIGN AND METHODS:
Longitudinal studies published in Medline, Embase, Social Science Citation Index, PsycINFO, and Social Policy and Practice were searched. No language restrictions were applied if there was an English abstract. Eighty-two longitudinal studies were included after critical appraisals.
RESULTS:
Studies in the United States often found no significant effect of retirement on CVD, while studies in European countries, except France, showed a detrimental effect of retirement on CVD. Results from the United States and several European countries consistently show that retirement increase adiposity measures among those retired from physically demanding jobs. For diabetes and hypertension, five out of nine studies suggest no effect of retirement. Retirement has been repeatedly linked to increasing leisure-time physical activity but may reduce work- and transport-related physical activity in turn. Most studies showed that retirement either decreased smoking or had no effect on smoking. The evidence did not show a clear conclusion on drinking. Only a few studies have assessed the impact on diet and blood biomarkers.
DISCUSSION AND IMPLICATIONS:
Effect of retirement varies according to the health outcomes studied and country of the study population. Policy concerning extending the retirement age needs to focus on ensuring they are suited to the individual.
KEYWORDS:
Cardiovascular disease; Drinking; Metabolic risk factors; Retired; Smoking

Dietary docosahexaenoic acid contributes to increased bone mineral accretion and strength in young female Sprague-Dawley rats.
Farahnak Z, Freundorfer MT, Lavery P, Weiler HA.
Prostaglandins Leukot Essent Fatty Acids. 2019 May;144:32-39. doi: 10.1016/j.plefa.2019.04.005. Epub 2019 Apr 22.
PMID: 31088624
Abstract
Growing evidence suggests that docosahexaenoic acid (DHA: 22:6n-3) enhances bone mineral content (BMC) and bone mineral density (BMD) in adulthood and during aging, however the effects during and after sexual maturation are unclear. The aim of this study was to examine the dose-response of BMC, BMD and microarchitectural properties of bone to dietary DHA in healthy growing female rats during acquisition of peak bone mass (PBM). Female Sprague-Dawley rats (n = 12/diet) were randomized to receive a control diet (AIN-93 M, 60 g soybean oil/kg diet) or an experimental diet containing 0.1, 0.4, 0.8 and 1.2% DHA (w/w of total diet) for 10 weeks. Dietary DHA increased the whole body, lumbar spine and long bone BMC compared to the control, in addition to higher aBMD and also BMD. Additionally, an increase in cortical bone microarchitecture parameters of lumbar spine as well as peak force were observed in dietary DHA diet groups. Dietary DHA contributes to PBM when consumed during and after sexual maturation, however higher doses of DHA do not provide further benefits.
KEYWORDS:
DHA; Dose-response; Growth; Peak bone mass

Prevalence, Incidence and Risk Factors for Overall, Physical and Cognitive Independence among those from exceptionally long-lived families: The Long Life Family Study.
Santanasto AJ, Marron MM, Boudreau RM, Feitosa MF, Wojczynski MK, Arbeev KG, Thyagarajan B, Schupf N, Stallard E, Sebastiani P, Cosentino S, Christensen K, Newman AB.
J Gerontol A Biol Sci Med Sci. 2019 May 14. pii: glz124. doi: 10.1093/gerona/glz124. [Epub ahead of print]
PMID: 31086986
https://sci-hub.tw/https://academic.oup.com/biomedgerontology/advance-article-abstract/doi/10.1093/gerona/glz124/5489046?redirectedFrom=fulltext
Abstract
BACKGROUND:
The Long Life Family Study (LLFS) enrolled families exhibiting exceptional longevity. The goal of this paper was to determine the prevalence and predictors of remaining independent after 7 years in the oldest generation.
METHODS:
We examined 7-year change in physical (free of ADL difficulty), cognitive (Mini Mental State Examination score≥24) and overall independence (physically/cognitively independent) in adults aged 90.3±6.3 from LLFS's oldest generation. Potential predictors (n = 28) of remaining independent included demographics, diseases, biomarkers, anthropometrics and physical/cognitive performance tasks and were determined using generalized estimating equations (α: p<0.05). This was a discovery/exploratory analysis, so no multiple testing correction was employed and the results require independent replication.
RESULTS:
At baseline (n=1442), 67.3%, 83.8% and 79.7% were overall, physically and cognitively independent, respectively. After 7 years, 66% died,7.5% were lost-to-follow-up and the prevalence of overall independence decreased, to 59.1% in survivors (-8.2%, 95% CI: -14.1, 2.2%). Of those with baseline independence, 156/226 (69.0%), remained independent. Predictors of remaining physically independent included younger age, better Short Physical Performance Battery (SPPB) score and lung function, smaller waist-circumference and lower soluble receptor for advanced glycation end-product (sRAGE) levels (p<0.05). Predictors of remaining cognitively independent included no cancer history, better Digit Symbol Substitution Test performance, and higher body weight (p<0.05).
CONCLUSIONS:
The prevalence of independence decreased by only 8.2% after 7 years, demonstrating the close correspondence between disability and mortality. Further, despite a mean baseline age of 90 years, a large proportion of survivors remained independent, suggesting this exceptional subgroup may harbor protective mechanisms.
KEYWORDS:
Compression of Morbidity; Dementia; Disability; Oldest Old

Association of habitual glucosamine use with risk of cardiovascular disease: prospective study in UK Biobank.
Ma H, Li X, Sun D, Zhou T, Ley SH, Gustat J, Heianza Y, Qi L.
BMJ. 2019 May 14;365:l1628. doi: 10.1136/bmj.l1628.
PMID: 31088786
Abstract
OBJECTIVE:
To prospectively assess the association of habitual glucosamine use with risk of cardiovascular disease (CVD) events.
DESIGN:
Prospective cohort study.
SETTING:
UK Biobank.
PARTICIPANTS:
466 039 participants without CVD at baseline who completed a questionnaire on supplement use, which included glucosamine. These participants were enrolled from 2006 to 2010 and were followed up to 2016.
MAIN OUTCOME MEASURES:
Incident CVD events, including CVD death, coronary heart disease, and stroke.
RESULTS:
During a median follow-up of seven years, there were 10 204 incident CVD events, 3060 CVD deaths, 5745 coronary heart disease events, and 3263 stroke events. After adjustment for age, sex, body mass index, race, lifestyle factors, dietary intakes, drug use, and other supplement use, glucosamine use was associated with a significantly lower risk of total CVD events (hazard ratio 0.85, 95% confidence interval 0.80 to 0.90), CVD death (0.78, 0.70 to 0.87), coronary heart disease (0.82, 0.76 to 0.88), and stroke (0.91, 0.83 to 1.00).
CONCLUSION:
Habitual use of glucosamine supplement to relieve osteoarthritis pain might also be related to lower risks of CVD events.

Effect of Milk and Other Dairy Products on the Risk of Frailty, Sarcopenia, and Cognitive Performance Decline in the Elderly: A Systematic Review.
Cuesta-Triana F, Verdejo-Bravo C, Fernández-Pérez C, Martín-Sánchez FJ.
Adv Nutr. 2018 May 1;10(suppl_2):S105-S119. doi: 10.1093/advances/nmy105.
PMID: 31089731
Abstract
Nutrition is a modifiable factor potentially related to aging. Milk and other dairy products may contribute to the prevention of physical and cognitive impairment. We conducted a systematic review to investigate the effectiveness of dairy product intake for preventing cognitive decline, sarcopenia, and frailty in the elderly population. A systematic search for publications in electronic databases [MEDLINE via PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews] from 2009 to 2018 identified observational and interventional studies in English and Spanish that tested the relation between dairy product consumption and cognitive decline, sarcopenia, and frailty in community-dwelling older people. We assessed the participants, the type of exposure or intervention, the outcomes, and the quality of evidence. We screened a total of 661 records and included 6 studies (5 observational prospective cohort studies and 1 randomized controlled trial). Regarding cognitive impairment, the relation cannot be firmly established. Consumption of milk at midlife may be negatively associated with verbal memory performance. In older women, high intakes of dairy desserts and ice cream were associated with cognitive decline. On the other hand, 1 study demonstrated a significant inverse relation between dairy intake and development of Alzheimer disease among older Japanese subjects. The consumption of dairy products by older people may reduce the risk of frailty, especially with high consumption of low-fat milk and yogurt, and may also reduce the risk of sarcopenia by improving skeletal muscle mass through the addition of nutrient-rich dairy proteins (ricotta cheese) to the habitual diet. Despite the scarcity of evidence on the topic, our systematic review shows that there are some positive effects of dairy products on frailty and sarcopenia, whereas studies concerning cognitive decline have contradictory findings.
KEYWORDS:
cognition; dairy products; dementia; frailty; milk; older; sarcopenia

Edited May 16, 2019 by AlPater

[AlPater]

Why doctors now warn against routinely treating mild thyroid issues
Treating a number 'doesn't make them better,' hormone specialist says
CBC News · Posted: May 17, 2019 4:00 AM ET | Last Updated: 4 hours ago
https://www.cbc.ca/news/health/hypothyroidism-subclinical-1.5138719
>>>>>>>>>>>>>>>>>>>>>>
Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline
BMJ 2019; 365 doi: https://doi.org/10.1136/bmj.l2006 (Published 14 May 2019)
https://www.bmj.com/content/365/bmj.l2006
Abstract
Clinical question What are the benefits and harms of thyroid hormones for adults with subclinical hypothyroidism (SCH)? This guideline was triggered by a recent systematic review of randomised controlled trials, which could alter practice.
Current practice Current guidelines tend to recommend thyroid hormones for adults with thyroid stimulating hormone (TSH) levels >10 mIU/L and for people with lower TSH values who are young, symptomatic, or have specific indications for prescribing.
Recommendation The guideline panel issues a strong recommendation against thyroid hormones in adults with SCH (elevated TSH levels and normal free T4 (thyroxine) levels). It does not apply to women who are trying to become pregnant or patients with TSH >20 mIU/L. It may not apply to patients with severe symptoms or young adults (such as those ≤30 years old).
How this guideline was created A guideline panel including patients, clinicians, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines using the GRADE approach.
The evidence The systematic review included 21 trials with 2192 participants. For adults with SCH, thyroid hormones consistently demonstrate no clinically relevant benefits for quality of life or thyroid related symptoms, including depressive symptoms, fatigue, and body mass index (moderate to high quality evidence). Thyroid hormones may have little or no effect on cardiovascular events or mortality (low quality evidence), but harms were measured in only one trial with few events at two years’ follow-up.
Understanding the recommendation The panel concluded that almost all adults with SCH would not benefit from treatment with thyroid hormones. Other factors in the strong recommendation include the burden of lifelong management and uncertainty on potential harms. Instead, clinicians should monitor the progression or resolution of the thyroid dysfunction in these adults. Recommendations are made actionable for clinicians and their patients through visual overviews. These provide the relative and absolute benefits and harms of thyroid hormones in multilayered evidence summaries and decision aids available in MAGIC (https://app.magicapp.org/) to support shared decisions and adaptation of this guideline.

Association between Bout Duration of Physical Activity and Health: Systematic Review.
Jakicic JM, Kraus WE, Powell KE, Campbell WW, Janz KF, Troiano RP, Sprow K, Torres A, Piercy KL; 2018 PHYSICAL ACTIVITY GUIDELINES ADVISORY COMMITTEE*.
Med Sci Sports Exerc. 2019 Jun;51(6):1213-1219. doi: 10.1249/MSS.0000000000001933.
PMID: 31095078
Abstract
PURPOSE:
This study aimed to conduct a systematic literature review to determine whether physical activity episodes of <10 min in duration have health-related benefits or, alternatively, if the benefits are only realized when the duration of physical activity episodes is ≥10 min.
METHODS:
The primary literature search was conducted for the 2018 Physical Activity Guidelines Advisory Committee Report and encompassed literature through June 2017, with an additional literature search conducted to include literature published through March 2018 for inclusion in this systematic review.
RESULTS:
The literature review identified 29 articles that were pertinent to the research question that used either cross-sectional, prospective cohort, or randomized designs. One prospective cohort study (N = 4840) reported similar associations between moderate to vigorous physical activity (MVPA) and all-cause mortality when examined as total MVPA, MVPA in bouts ≥5 min in duration, or MVPA in bouts ≥10 min in duration. Additional evidence was identified from cross-sectional and prospective studies to support that bouts of physical activity <10 min in duration are associated with a variety of health outcomes. Randomized studies only examined bouts of physical activity ≥10 min in duration.
CONCLUSIONS:
The current evidence, from cross-sectional and prospective cohort studies, supports that physical activity of any bout duration is associated with improved health outcomes, which includes all-cause mortality. This may suggest the need for a contemporary paradigm shift in public health recommendations for physical activity, which supports total MVPA as an important lifestyle behavior regardless of the bout duration.

Loneliness, living alone, and all-cause mortality: The role of emotional and social loneliness in the elderly during 19 years of follow-up.
O'Súilleabháin PS, Gallagher S, Steptoe A.
Psychosom Med. 2019 May 13. doi: 10.1097/PSY.0000000000000710. [Epub ahead of print]
PMID: 31094903
Abstract
OBJECTIVE:
To examine the predictive value of social and emotional loneliness for all-cause mortality in the oldest-old who do, and do not live alone and to test whether these varied by functional status and personality.
METHODS:
Participants were 413 older adults from the Berlin Aging Study (M ± SD = 84.53 ± 8.61 years of age) who either lived alone (n = 253) or did not live alone (n = 160). Significance values for hazard ratios are reported having adjusted for age, sex, education, income, marital status, depressive illness, and both social and emotional loneliness.
RESULTS:
While social loneliness was not associated with mortality in those living alone, emotional loneliness was; with each 1 SD increase in emotional loneliness there was a 18.6% increased risk of all-cause mortality in the fully adjusted model (HR = 1.186; p = 0.029). No effects emerged for social or emotional loneliness for those not living alone. No associations emerged for social or emotional loneliness among those not living alone. Examinations of potential moderators revealed that with each 1 SD increase in functional status, the risk associated with emotional loneliness for all-cause mortality increased by 17.9% (HRinteraction = 1.179; p = 0.005) in those living alone. No interaction between personality traits with loneliness emerged.
CONCLUSIONS:
Emotional loneliness is associated with an increased risk of all-cause mortality in older aged adults who live alone. Functional status was identified as one potential pathway of accounting for the adverse consequences of loneliness. Emotional loneliness that can arise out of the loss or absence of a close emotional attachment figure appears to be the toxic component of loneliness.

Association between Dietary Intakes of B Vitamins in Midlife and Cognitive Impairment in Late-Life: the Singapore Chinese Health Study.
Sheng LT, Jiang YW, Pan XF, Feng L, Yuan JM, Pan A, Koh WP.
J Gerontol A Biol Sci Med Sci. 2019 May 15. pii: glz125. doi: 10.1093/gerona/glz125. [Epub ahead of print]
PMID: 31094422
https://sci-hub.tw/10.1093/gerona/glz125
Abstract
BACKGROUND:
Dietary intakes of B vitamins (e.g., folate) are related to cognitive function according to epidemiologic studies in western countries. But prospective studies in Asian populations are scarce. This study evaluated the relations of dietary intakes of six B vitamins in midlife with cognitive impairment in old age in a Chinese population living in Singapore.
METHODS:
This study included 16,948 participants from the Singapore Chinese Health Study, a population-based prospective cohort. Baseline dietary intakes of B vitamins were assessed using a validated 165-item food frequency questionnaire when the participants were 45-74 years (1993-1998). After an average follow-up of 20 years, cognitive function was examined using a Singapore-modified version of Mini-Mental State Examination (SM-MMSE) scale in 2014-2016, and cognitive impairment was defined using education-specific cut-offs. Logistic regression models were applied to estimate the association between B vitamins and cognitive impairment. All the six B vitamins were mutually adjusted in the final model.
RESULTS:
In the 2014-2016 interview, 2,443 participants were defined as cognitive impairment. Riboflavin and folate were significantly and independently associated with cognitive impairment in a dose-dependent manner: the odds ratio (95% confidence interval) comparing the highest with the lowest quartile was 0.82 (0.69, 0.97) for riboflavin, and 0.83 (0.70, 0.98) for folate (both p-trend <.05). Dietary intakes of thiamine, niacin, vitamin B-6 and B-12 were not significantly associated with risk of cognitive impairment.
CONCLUSIONS:
Higher dietary intakes of riboflavin and folate in midlife were associated with a lower risk of cognitive impairment in late-life in the Chinese population.
KEYWORDS:
Cognitive Function; Cohort Study; Folate; MMSE; Riboflavin

[AlPater]

The association of vascular disorders with incident dementia in different age groups.
Legdeur N, van der Lee SJ, de Wilde M, van der Lei J, Muller M, Maier AB, Visser PJ.
Alzheimers Res Ther. 2019 May 17;11(1):47. doi: 10.1186/s13195-019-0496-x.
PMID: 31097030
https://alzres.biomedcentral.com/track/pdf/10.1186/s13195-019-0496-x
Abstract
BACKGROUND:
There is increasing evidence that dementia risk associated with vascular disorders is age dependent. Large population-based studies of incident dementia are necessary to further elucidate this effect. Therefore, the aim of the present study was to determine the association of vascular disorders with incident dementia in different age groups in a large primary care database.
METHODS:
We included 442,428 individuals without dementia aged ≥ 65 years from the longitudinal primary care Integrated Primary Care Information (IPCI) database. We determined in 6 age groups (from 65-70 to ≥ 90 years) the risk of hypertension, diabetes mellitus, dyslipidemia, stroke, myocardial infarction, heart failure, and atrial fibrillation for all-cause dementia using incidence rate ratios, Cox regression, and Fine and Gray regression models.
RESULTS:
The mean age at inclusion of the total study sample was 72.4 years, 45.7% of the participants were male, and median follow-up was 3.6 years. During 1.4 million person-years of follow-up, 13,511 individuals were diagnosed with dementia. The risk for dementia decreased with increasing age for all risk factors and was no longer significant in individuals aged ≥ 90 years. Adjusting for mortality as a competing risk did not change the results.
CONCLUSIONS:
We conclude that vascular disorders are no longer a risk factor for dementia at high age. Possible explanations include selective survival of individuals who are less susceptible to the negative consequences of vascular disorders and differences in follow-up time between individuals with and without a vascular disorder. Future research should focus on the identification of other risk factors than vascular disorders, for example, genetic or inflammatory processes, that can potentially explain the strong age-related increase in dementia risk.
KEYWORDS:
Aging; Cardiovascular risk factors; Dementia; Primary care; Vascular disease; Vascular disorders

Safety and efficacy of aspirin for primary prevention of cancer: a meta-analysis of randomized controlled trials.
Haykal T, Barbarawi M, Zayed Y, Yelangi A, Dhillon H, Goranta S, Kheiri B, Chahine A, Samji V, Kerbage J, Katato K, Bachuwa G.
J Cancer Res Clin Oncol. 2019 May 16. doi: 10.1007/s00432-019-02932-0. [Epub ahead of print] Review.
PMID: 31098750
https://sci-hub.tw/https://link.springer.com/article/10.1007/s00432-019-02932-0

Dietary fats and cardiometabolic disease: mechanisms and effects on risk factors and outcomes.
Wu JHY, Micha R, Mozaffarian D.
Nat Rev Cardiol. 2019 May 16. doi: 10.1038/s41569-019-0206-1. [Epub ahead of print] Review.
PMID: 31097791
https://sci-hub.tw/10.1038/s41569-019-0206-1
Abstract
The effect of dietary fats on cardiometabolic diseases, including cardiovascular diseases and type 2 diabetes mellitus, has generated tremendous interest. Many earlier investigations focused on total fat and conventional fat classes (such as saturated and unsaturated fats) and their influence on a limited number of risk factors. However, dietary fats comprise heterogeneous molecules with diverse structures, and growing research in the past two decades supports correspondingly complex health effects of individual dietary fats. Moreover, health effects of dietary fats might be modified by additional factors, such as accompanying nutrients and food-processing methods, emphasizing the importance of the food sources. Accordingly, the rapidly increasing scientific findings on dietary fats and cardiometabolic diseases have generated debate among scientists, caused confusion for the general public and present challenges for translation into dietary advice and policies. This Review summarizes the evidence on the effects of different dietary fats and their food sources on cell function and on risk factors and clinical events of cardiometabolic diseases. The aim is not to provide an exhaustive review but rather to focus on the most important evidence from randomized controlled trials and prospective cohort studies and to highlight current areas of controversy and the most relevant future research directions for understanding how to improve the prevention and management of cardiometabolic diseases through optimization of dietary fat intake.

Three consecutive weeks of nutritional ketosis has no effect on cognitive function, sleep, and mood compared with a high-carbohydrate, low-fat diet in healthy individuals: a randomized, crossover, controlled trial.
Iacovides S, Goble D, Paterson B, Meiring RM.
Am J Clin Nutr. 2019 May 16. pii: nqz073. doi: 10.1093/ajcn/nqz073. [Epub ahead of print]
PMID: 31098615
Abstract
BACKGROUND:
The high-fat ketogenic diet (KD) has become an increasingly popular diet not only in overweight/obese populations, or those with clinical conditions, but also in healthy non-overweight populations.
OBJECTIVE:
Because there are concerns about the association between high-fat diets and cognitive decline, this study aimed to determine the effects of a KD compared with an isocaloric high-carbohydrate, low-fat (HCLF) diet on cognitive function, sleep, and mood in healthy, normal-weight individuals.
METHODS:
Eleven healthy, normal-weight participants (mean age: 30 ± 9 y) completed this randomized, controlled, crossover study. Participants followed 2 isocaloric diets-an HCLF diet (55% carbohydrate, 20% fat, and 25% protein) and a KD (15% carbohydrate, 60% fat, and 25% protein)-in a randomized order for a minimum of 3 wk, with a 1-wk washout period between diets. Measures of β-hydroxybutyrate confirmed that all participants were in a state of nutritional ketosis during post-KD assessments (baseline: 0.2 ± 0.2 mmol/L; KD: 1.0 ± 0.5 mmol/L; washout: 0.2 ± 0.1 mmol/L; and HCLF: 0.3 ± 0.2 mmol/L). Cognitive function was assessed using a validated, psychological computer-based test battery before and after each diet. Subjective measures of mood and sleep were also monitored throughout the study using validated scales.
RESULTS:
Three weeks of sustained nutritional ketosis, compared with the HCLF diet, had no effect on speed and accuracy responses in tasks designed to measure vigilance (speed: P = 0.39, Cohen's d = 0.26; accuracy: P = 0.99, Cohen's d = 0.04), visual learning and memory (speed: P = 0.99, Cohen's d = 0.04; accuracy: P = 0.99, Cohen's d = 0.03), working memory (speed: P = 0.62, Cohen's d = 0.26; accuracy: P = 0.98, Cohen's d = 0.07), and executive function (speed: P = 0.60, Cohen's d = 0.31; accuracy: P = 0.90, Cohen's d = 0.19). Likewise, mood, sleep quality, and morning vigilance did not differ (P > 0.05) between the dietary interventions.
CONCLUSION:
The results of our randomized, crossover, controlled study suggest that 3 wk of sustained nutritional ketosis had no effect on cognitive performance, mood, or subjective sleep quality in a sample of healthy individuals.
KEYWORDS:
cognitive function; healthy subjects; memory; mood; nutritional ketosis; sleep; visual function

Association of Sugary Beverage Consumption With Mortality Risk in US Adults: A Secondary Analysis of Data From the REGARDS Study.
Collin LJ, Judd S, Safford M, Vaccarino V, Welsh JA.
JAMA Netw Open. 2019 May 3;2(5):e193121. doi: 10.1001/jamanetworkopen.2019.3121.
PMID: 31099861
Abstract
IMPORTANCE:
Research has linked sugar-sweetened beverage (SSB) consumption to coronary heart disease (CHD) risk, but the role of nutritionally similar fruit juice and the association of these beverages with mortality risk is unknown.
OBJECTIVE:
To assess the association of SSBs and 100% fruit juices, alone and in combination (sugary beverages), with mortality.
DESIGN, SETTING, AND PARTICIPANTS:
This cohort study is a secondary analysis of data obtained from 30 183 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. The REGARDS study was designed to examine modifiers of stroke risk. Enrollment took place from February 2003 to October 2007, with follow-up every 6 months through 2013. Overall, 30 183 non-Hispanic black and white adults 45 years and older were enrolled in the REGARDS study. Those with known CHD, stroke, or diabetes at baseline (12 253 [40.6%]) and those lacking dietary data (4490 [14.9%]) were excluded from the current study, resulting in a sample size of 13 440. Data were analyzed from November 2017 to December 2018.
EXPOSURES:
Sugar-sweetened beverage and 100% fruit juice consumption was estimated using a validated food frequency questionnaire and examined using categories of consumption that align with recommended limits for added sugar intake as a percentage of total energy (TE; <5%, 5%-<10%, and ≥10%) and 12-oz serving increments.
MAIN OUTCOMES AND MEASURES:
All-cause and CHD-specific mortality were determined from cause of death records and family interviews and adjudicated by a trained team. Multivariable adjusted hazard ratios (HRs) were estimated using regression models.
RESULTS:
Overall, 13 440 participants had a mean (SD) age of 63.6 (9.1) years at baseline, 7972 (59.3%) were men, 9266 (68.9%) were non-Hispanic white, and 9482 (70.8%) had overweight or obesity. There were 1000 all-cause and 168 CHD-related deaths during follow-up (mean [SD] follow-up, 6.0 [1.8] years). Mean (SD) sugary beverage consumption was 8.4% (8.3%) of TE/d (4.4% [6.8%] TE/d from SSBs; 4.0% [6.8%] TE/d from 100% fruit juice). Among high (≥10% of TE) vs low (<5% of TE) sugary beverage consumers, risk-adjusted HRs were 1.44 (95% CI, 0.97-2.15) for CHD mortality and 1.14 (95% CI, 0.97-1.33) for all-cause mortality. Risk-adjusted all-cause mortality HRs were 1.11 (95% CI, 1.03-1.19) for each additional 12 oz of sugary beverage consumed and 1.24 (95% CI, 1.09-1.42) for each additional 12 oz of fruit juice consumed. In risk-adjusted models, there was no significant association of sugary beverage consumption with CHD mortality.
CONCLUSIONS AND RELEVANCE:
These findings suggest that consumption of sugary beverages, including fruit juices, is associated with all-cause mortality. Well-powered and longer-term studies are needed to inform their association with CHD mortality risk.

[AlPater]

Don't call it 'dieting': Silicon Valley's next big hack might happen in your body
'It seems like the self is the next device,' says tech writer Amanda Mull
CBC Radio · Posted: May 17, 2019 5:36 PM ET | Last Updated: May 17
https://www.cbc.ca/radio/day6/canada-s-anti-abortion-movement-kids-named-khaleesi-israel-s-cybersecurity-sector-rita-chiarelli-and-more-1.5138387/don-t-call-it-dieting-silicon-valley-s-next-big-hack-might-happen-in-your-body-1.5138394

Postprandial Lipemic Responses to Various Sources of Saturated and Monounsaturated Fat in Adults.
Sciarrillo CM, Koemel NA, Tomko PM, Bode KB, Emerson SR.
Nutrients. 2019 May 16;11(5). pii: E1089. doi: 10.3390/nu11051089.
PMID: 31100881
https://www.mdpi.com/2072-6643/11/5/1089/htm
Abstract
BACKGROUND:
Postprandial lipemia (PPL) is a cardiovascular disease risk factor. However, the effects of different fat sources on PPL remain unclear. We aimed to determine the postprandial response in triglycerides (TG) to four dietary fat sources in adults.
METHODS:
Participants completed four randomized meal trials. For each meal trial, participants (n = 10; 5M/5F) consumed a high-fat meal (HFM) (13 kcal/kg; 61% of total kcal from fat) with the fat source derived from butter, coconut oil, olive oil, or canola oil. Blood was drawn hourly for 6 h post-meal to quantify PPL.
RESULTS:
Two-way ANOVA of TG revealed a time effect (p < 0.0001), but no time-meal interaction (p = 0.56), or meal effect (p = 0.35). Meal trials did not differ with regard to TG total (p = 0.33) or incremental (p = 0.14) area-under-the-curve. When stratified by sex and the TG response was averaged across meals, two-way ANOVA revealed a time effect (p < 0.0001), time-group interaction (p = 0.0001), and group effect (p = 0.048), with men exhibiting a greater response than women, although this difference could be attributed to the pronounced difference in BMI between men and women within the sample.
CONCLUSION:
In our sample of young adults, postprandial TG responses to a single HFM comprised of different fat sources did not differ.
KEYWORDS:
butter; canola oil; cardiovascular disease; coconut oil; dietary fat; lipid; olive oil; postprandial lipemia; saturated fat; triglycerides

[AlPater]

Circulating levels of the components of the GH/IGF-1/IGFBPs axis total and intact IGF-binding proteins (IGFBP) 3 and IGFBP 4 and total IGFBP5, as well as PAPPA, PAPPA2 and Stanniocalcin-2 levels are not altered in response to energy deprivation and/or metreleptin administration in humans.
Pilitsi E, Peradze N, Perakakis N, Mantzoros CS.
Metabolism. 2019 May 16. pii: S0026-0495(19)30092-7. doi: 10.1016/j.metabol.2019.05.004. [Epub ahead of print]
PMID: 31103608
https://sci-hub.tw/10.1016/j.metabol.2019.05.004
Abstract
OBJECTIVE:
It remains unclear whether food deprivation induces changes in components of the GH/IGF-1/IGFBPs axis and if yes, which ones are mediated by leptin, an adipocyte secreted hormone regulating neuroendocrine response to energy deprivation in animals and humans. We aimed to investigate components of the axis that have not been studied to date, i.e. IGF-binding proteins (IGFBPs) and related proteases (total and intact IGFBP 3 and IGFBP 4, total IGFBP5, PAPPA, PAPPA2 and Stanniocalcin-2), during acute (short-term fasting in healthy subjects) and chronic (women with hypothalamic amenorrhea [HA] due to excessive exercise) energy deprivation and whether metreleptin administration, in replacement, supraphysiologic or pharmacologic levels, may mediate any changes of circulating levels of the above molecules in healthy individuals and in women with hypothalamic amenorrhea.
METHODS:
We studied: 1) 11 healthy men and women during three four day admissions i.e. a baseline admission in the fed isocaloric state and two admissions in the complete food deprivation state for 72-h with either placebo (resulting in a hypoleptinemic state) or metreleptin administration in doses designed to normalize circulating leptin levels for the duration of the study, 2) 15 healthy men and women during three 72-h long admissions in a complete food deprivation state receiving three escalating doses of metreleptin designed to bring circulating leptin levels to physiologic, supraphysiologic, or pharmacologic levels, and 3) 18 women with HA randomized to either metreleptin treatment in replacement doses or placebo for nine months.
RESULTS:
There were no significant changes in the circulating profiles of the above molecules in the fasting vs. fed state and/or with metreleptin administration during acute and chronic energy deprivation.
CONCLUSIONS:
The studied components of the GH/IGF-1/IGFBPs axis are not affected by energy deprivation, leptin deficiency associated with energy deprivation, or by metreleptin administration in physiologic, supraphysiologic or pharmacologic doses.
KEYWORDS:
Fasting; Hypothalamic amenorrhea; IGFBPs; Leptin; PAPPA; Stanniocalcin-2

[AlPater]

The association of resistance training with mortality: A systematic review and meta-analysis.
Saeidifard F, Medina-Inojosa JR, West CP, Olson TP, Somers VK, Bonikowske AR, Prokop LJ, Vinciguerra M, Lopez-Jimenez F.
Eur J Prev Cardiol. 2019 May 19:2047487319850718. doi: 10.1177/2047487319850718. [Epub ahead of print]
PMID: 31104484
Abstract
BACKGROUND:
The benefits of aerobic exercise are well-studied; there is no consensus on the association between resistance training and major adverse cardiovascular outcomes. This systematic review and meta-analysis aimed to address this issue.
DESIGN AND METHODS:
We searched for randomized trials and cohort studies that evaluated the association between resistance training and mortality and cardiovascular events. Two investigators screened the identified abstracts and full-texts independently and in duplicate. Cochrane tools were used to assess the risk of bias. We calculated hazard ratios and 95% confidence intervals using random effect models.
RESULTS:
From the 1430 studies identified, 11 (one randomized trial and 10 cohort studies) met the inclusion criteria, totaling 370,256 participants with mean follow-up of 8.85 years. The meta-analysis showed that, compared with no exercise, resistance training was associated with 21% (hazard ratio (95% confidence interval (CI)), 0.79 (0.69-0.91)) and 40% (hazard ratio (95% CI), 0.60 (0.49-0.72)) lower all-cause mortality alone and when combined with aerobic exercise, respectively. Furthermore, resistance training had a borderline association with lower cardiovascular mortality (hazard ratio (95% CI), 0.83 (0.67-1.03)). In addition, resistance training showed no significant association with cancer mortality. Risk of bias was low to intermediate in the included studies. One cohort study looked at the effect of resistance training on coronary heart disease events in men and found a 23% risk reduction (risk ratio, 0.77, CI: 0.61-0.98).
CONCLUSION:
Resistance training is associated with lower mortality and appears to have an additive effect when combined with aerobic exercise. There are insufficient data to determine the potential beneficial effect of resistance training on non-fatal events or the effect of substituting aerobic exercise with resistance training.
KEYWORDS:
Resistance training; cardiovascular outcome; meta-analysis; mortality; strength training; systematic review

Erectile Dysfunction Predicts Cardiovascular Events as an Independent Risk Factor: A Systematic Review and Meta-Analysis.
Zhao B, Hong Z, Wei Y, Yu D, Xu J, Zhang W.
J Sex Med. 2019 May 16. pii: S1743-6095(19)31115-4. doi: 10.1016/j.jsxm.2019.04.004. [Epub ahead of print]
PMID: 31104857
Abstract
INTRODUCTION:
Previous studies demonstrating that erectile dysfunction (ED) predicts the risk of further cardiovascular events (CV) events are insufficient to make recommendations for cardiologists, diabetologists, urologists, and more, and the association between CV events and ED degree is unclear.
AIM:
To assess whether ED was a risk factor for CV events in a comprehensive literature review and meta-analysis.
METHODS:
PubMed, EMBASE, the Cochrane Library, Medline, and the Web of Science were searched for eligible studies. The protocol for this meta-analysis is available from PROSPERO (CRD42018086138).
MAIN OUTCOME MEASURES:
The main outcomes included cardiovascular disease (CVD), coronary heart disease (CHD), stroke, and all-cause mortality. Subgroup and sensitivity analyses were conducted to detect potential bias.
RESULTS:
25 eligible studies involving 154,794 individuals were included in our meta-analysis. Compared with those of men without ED, the CVD risk of ED patients was significantly increased by 43% (relative risk [RR] =1.43; P < .001), CHD was increased by 59% (RR = 1.59; P < .001), stroke was increased by 34% (RR = 1.34; P < .001), and all-cause mortality was increased by 33% (RR = 1.33; P < .001). Older individuals with ED (≥55 years), those with ED of a shorter duration (<7 years), and those with higher rates of diabetes (≥20%) and smoking (≥40%) were more prone to develop CVD. Additionally, severe ED was proven to predict higher CVD and all-cause mortality risk. The standardized model proposed here can be properly applied for screening early CV events.
CLINICAL IMPLICATIONS:
The evidence prompts the diligent observation of at-risk men and reinforces the importance of early treatment to prevent CV events.
STRENGTHS & LIMITATIONS:
Larger sample sizes from recent prospective cohort studies were included to provide more up-to-date, reliable, and comprehensive results. Moreover, the results were robust regarding consistency across sensitivity and subgroup analyses and remained consistent; even pre-excluded retrospective or cross-sectional studies were included. We constructed a standardized model that addresses the study's innovations and implications for the first time. However, not all included studies were randomized controlled trials, which might downgrade this evidence.
CONCLUSIONS:
Risk of total CVD, CHD, stroke, and all-cause mortality was significantly increased in populations with ED, and severe ED is of particular concern. The evidence suggests the need for diligent observation of at-risk men and reinforces the importance of early treatment to prevent CV events.
KEYWORDS:
Cardiovascular Disease; Coronary Heart Disease; Erectile Dysfunction; Meta-Analysis; Stroke

Associations between coffee consumption and all-cause and cause-specific mortality in a Japanese city: the Takayama study.
Yamakawa M, Wada K, Goto Y, Mizuta F, Koda S, Uji T, Nagata C.
Public Health Nutr. 2019 May 20:1-8. doi: 10.1017/S1368980019000764. [Epub ahead of print]
PMID: 31107195
Abstract
OBJECTIVE:
Epidemiological studies suggest that coffee consumption is inversely associated with all-cause and cause-specific mortality. Evidence from studies targeting non-white, non-Western populations is still sparse, although coffee is popular and widely consumed in Asian countries.
DESIGN:
Population-based, prospective cohort study. We used Cox proportional hazards models with adjustment for dietary and lifestyle factors to estimate associations between coffee consumption and all-cause and cause-specific mortality. Dietary intake including coffee consumption was assessed only at baseline using a validated FFQ.
SETTING:
A Japanese city.
PARTICIPANTS:
Individuals aged 35 years or older without cancer, CHD and stroke at baseline (n 29 079) and followed from 1992 to 2008.
RESULTS:
From 410 352 person-years, 5339 deaths were identified (mean follow-up = 14·1 years). Coffee consumption was inversely associated with mortality from all causes and CVD among all participants, but not from cancer. Compared with the category of 'none', the multivariate hazard ratio (95 % CI) for all-cause mortality was 0·93 (0·86, 1·00) for &lt;1 cup/d, 0·84 (0·76, 0·93) for 1 cup/d and 0·81 (0·71, 0·92) for 2-3 cups/d. The multivariate hazard ratio (95 % CI) for cardiovascular mortality were 0·87 (0·77, 0·99) for &lt;1 cup/d, 0·76 (0·63, 0·92) for 1 cup/d and 0·67 (0·50, 0·89) for 2-3 cups/d. Inverse associations were also observed for mortality from other causes, specifically infectious and digestive diseases.
CONCLUSION:
Drinking coffee, even 1 cup/d, was inversely associated with all-cause mortality and mortality from cardiovascular, infectious and digestive diseases.
KEYWORDS:
Asia; Coffee; Cohort studies; Mortality; Prospective studies

The longitudinal impact of diet, physical activity, sleep, and screen time on Canadian adolescents' academic achievement: An analysis from the COMPASS study.
Faught EL, Qian WBK, Carson VL, Storey KE, Faulkner G, Veugelers PJ, Leatherdale ST.
Prev Med. 2019 May 17. pii: S0091-7435(19)30175-6. doi: 10.1016/j.ypmed.2019.05.007. [Epub ahead of print]
PMID: 31108133
https://reader.elsevier.com/reader/sd/pii/S0091743519301756?token=295A9346F3E7692658DE4A3AC10F6172A30408596D9CA2BFA459954D34A6E1512611ED0FC2C753AADAD3343981A26531
Abstract
Adequate amounts of physical activity, sleep, and screen time along with a healthy diet have been demonstrated to have positive associations with academic achievement. No longitudinal study has investigated the simultaneous relationship between all of these behaviours and academic achievement. Data from 11,016 adolescent participants of the COMPASS study in Alberta and Ontario were analysed. Students self-reported their adherence to Canadian recommendations for health behaviours and academic achievement in Math and English on school-based surveys administered in the 2015/16 and 2016/17 waves of COMPASS. Multinomial generalized estimating equations were used to evaluate the association between longitudinal changes in adherence to recommendations and academic achievement at follow-up. Models were adjusted for self-reported sociodemographic information, body weight status, and baseline academic achievement. Students who adhered to a greater number of recommendations performed better than students who adhered to fewer recommendations. Meeting recommendations for Meat and Alternatives (protein-rich foods) and screen time were consistently associated with higher academic achievement compared to students who did not meet these recommendations. A change from not meeting recommendations for Vegetables and Fruit to meeting the recommendation in the following year was associated with higher achievement in both subjects. There was no association between sleep behaviours or physical activity and academic achievement. Results indicate that adherence to recommendations for protein-rich foods, screen time, and vegetables and fruit show promise as behavioural targets for higher academic achievement among youth. Further study using objectives measurements of behaviours and further consideration of socioeconomic variables is merited.
KEYWORDS:
Academic achievement; Adolescent health; Childhood obesity; Diet; Physical activity; School health; Screen time; Sleep

[AlPater]

Occupational physical activity and all-cause and cardiovascular disease mortality: Results from two longitudinal studies in Switzerland.
Wanner M, Lohse T, Braun J, Cabaset S, Bopp M, Krause N, Rohrmann S, For The Swiss National Cohort Study Group.
Am J Ind Med. 2019 May 20. doi: 10.1002/ajim.22975. [Epub ahead of print]
PMID: 31111529
Abstract
BACKGROUND:
Research regarding the effects of occupational physical activity on health remains inconsistent. We analyzed the association of occupational physical activity with all-cause and cardiovascular disease (CVD) mortality.
METHODS:
We analyzed two cohorts with baseline assessments from 1977 to 1993 ("National Research Program 1A" (NRP1A) and "MONItoring of trends and determinants in CArdiovascular disease" [MONICA]) and mortality follow-up until 2015 using adjusted Cox regression models.
RESULTS:
We included 4396 NRP1A participants (137 793 person-years of follow-up, 1541 deaths) and 5780 MONICA participants (135 410 person-years, 1158 deaths). All-cause mortality was higher for men in the high compared with the low occupational physical activity category according to NRP1A (hazard ratio {HR} 1.25, 95% confidence intervals [CI] 1.05-1.50). CVD mortality was higher for men in the moderate compared with the low occupational physical activity category according to MONICA (HR, 1.41; 95% CI, 1.03-1.91). Results for women were not statistically significant.
CONCLUSIONS:
We observed higher total and CVD mortality risks in men with higher occupational physical activity but inconsistent results for women and across cohorts.
KEYWORDS:
MONICA; National Research Program 1A (NRP1A); linkage, Swiss National Cohort; work-related physical activity

Long-Term Clinical Outcomes of Radical Prostatectomy versus Watchful Waiting in Localized Prostate Cancer Patients: A Systematic Review and Meta-Analysis.
Nouhi M, Mousavi SM, Olyaeemanesh A, Shaksisalim N, Akbari Sari A.
Iran J Public Health. 2019 Apr;48(4):566-578. Review.
PMID: 31110967
Abstract
BACKGROUND:
The present study aimed to compare the long-term clinical and functional outcomes of patients with clinically localized prostate cancer treated with radical prostatectomy compared to the watchful waiting.
METHODS:
PubMed, Cochrane Central Register of Controlled Trials and reference lists of relevant marker studies were scrutinized from inception to Jan 2018. Two reviewers conducted data abstraction and quality assessment of included trials independently. Quality of included studies were assessed by using Cochrane checklist. Inverse-variance and Mantel-Haenszel estimates under random effects model were used to pool results as relative risks with 95% confidence interval. Heterogeneity was assessed by using I2.
RESULTS:
Three randomized controlled trials with 1568 participants were included. Compared to watchful waiting, radical prostatectomy had no significant effect on all-cause mortality at 12-year follow-up. However, radical prostatectomy had significant effect on reducing prostate-cause mortality at 12-year follow-up. We found significant lower prostate-cause mortality in patients with PSA>10 and GS≥7 scores who had undergone radical prostatectomy compared with patients in watchful waiting group. In addition, younger patients undergoing surgery developed lower distant metastases rate compared to another approach. Watchful waiting had a significant effect on erectile and urinary incontinence during 2 years.
CONCLUSION:
There was no significant difference between radical prostatectomy and watchful waiting on all-cause mortality. However, the radical prostatectomy was associated with statistically lower prostate-cause mortality and metastases rates. Compared with older men, younger men experienced better clinical outcomes. Moreover, watchful waiting had better effect on reducing erectile dysfunction and urinary incontinence among patients during 2 years compared to radical prostatectomy.
KEYWORDS:
Clinical outcomes; Prostate cancer; Radical prostatectomy; Systematic review

Edited May 22, 2019 by AlPater

[AlPater]

A prospective study of dairy product intake and the risk of hepatocellular carcinoma in U.S. men and women.
Yang W, Sui J, Ma Y, Simon TG, Chong D, Meyerhardt JA, Willett WC, Giovannucci EL, Chan AT, Zhang X.
Int J Cancer. 2019 May 22. doi: 10.1002/ijc.32423. [Epub ahead of print]
PMID: 31116416
https://sci-hub.tw/10.1002/ijc.32423
Abstract
Although increasing dairy product intake has been associated with risk of several cancers, epidemiological studies on hepatocellular carcinoma are sparse and have yielded inconsistent results. We prospectively assessed the associations of dairy products (total, milk, butter, cheese, and yogurt) and their major components (calcium, vitamin D, fats, and protein) with the risk of hepatocellular carcinoma development among 51,418 men and 93,427 women in the Health Professionals Follow-up Study and the Nurses' Health Study. Diets were collected at baseline and updated every 2-4 years using validated food frequency questionnaires. Multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using Cox proportional hazards regression model. During up to 32 years of follow-up, a total of 164 hepatocellular carcinoma cases were documented. After adjustment for most known hepatocellular carcinoma risk factors, higher total dairy product intake was associated with an increased risk of hepatocellular carcinoma (highest vs. lowest tertile, HR=1.85, 95%CI: 1.19-2.88; Ptrend =0.009). For the same comparison, we observed significant positive associations of high-fat dairy (HR=1.81, 95%CI: 1.19-2.76; Ptrend =0.008) and butter (HR=1.58, 95%CI: 1.06-2.36; Ptrend =0.04) with hepatocellular carcinoma risk. There was a non-significant inverse association between yogurt intake and hepatocellular carcinoma risk (HR=0.72, 95%CI: 0.49-1.05; Ptrend =0.26). Our data suggest that higher intake of high fat dairy foods was associated with higher, whereas higher yogurt consumption might be associated with lower risk of developing hepatocellular carcinoma among U.S. men and women. This article is protected by copyright. All rights reserved.
KEYWORDS:
cancer; cancer prevention; cohort study; dairy products; hepatocellular carcinoma; milk

[AlPater]

Association between vitamin D and risk of cardiovascular disease in Chinese rural population.
Wang T, Sun H, Ge H, Liu X, Yu F, Han H, Wang J, Li W.
PLoS One. 2019 May 23;14(5):e0217311. doi: 10.1371/journal.pone.0217311. eCollection 2019.
PMID: 31120983
https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0217311&type=printable
Abstract
Previous studies have suggested that vitamin D is associated with cardiovascular disease (CVD), however, the relationship between vitamin D levels and CVD risk is still unclear. The purpose of this study was to assess the relationship of serum concentration of 25-hydroxyvitamin D (25(OH)D) with CVD in rural residents of Henan province of China. Basic information and medical history were gathered through face-to-face surveys from July 2013 to August 2015, and biochemical indicators were gathered in a laboratory setting. Logistic and restricted cubic splines regression analyses were used to estimate odd ratios (ORs) and 95% confidence intervals (95%CI) of CVD. A total of 1078 participants were included, the mean serum 25(OH)D concentration was determined to be 25 ± 18 ng/ml, with 54.45% of the participants presenting vitamin D deficiency [25(OH)D < 20 ng/mL]. Moreover, the prevalence of CVD was 59.28% in the vitamin D deficient group, which was higher than in the insufficient (48.55%) and sufficient groups (52.78%). After adjusting for potential confounders, compared with the deficient group, the ORs (95%CI) of CVDs were 0.68 (0.50, 0.91) in the insufficient group and 0.81 (0.56, 1.16) in the sufficient group. A nonlinear (U-shaped) association was observed between the risk of CVD and 25(OH)D concentration. Further research suggested that the risk of CVD was higher in males than in females. In conclusion, a U-shape association between serum levels of 25(OH)D and the risk of CVD was identified in our study, suggesting a nonlinear relationship between vitamin D with the prevalence of CVD.

Fish and Meat Intake, Serum Eicosapentaenoic Acid and Docosahexaenoic Acid Levels, and Mortality in Community-Dwelling Japanese Older Persons.
Otsuka R, Tange C, Nishita Y, Tomida M, Kato Y, Imai T, Ando F, Shimokata H.
Int J Environ Res Public Health. 2019 May 21;16(10). pii: E1806. doi: 10.3390/ijerph16101806.
PMID: 31117268
https://www.mdpi.com/1660-4601/16/10/1806/htm
Abstract
The associations between meat/fish consumption, docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) intakes, and blood DHA/EPA levels, and mortality in Japan were examined as part of the National Institute for Longevity Sciences-Longitudinal Study of Aging: 520 men and 534 women (60-79 years at baseline) were followed from 1997-2017. Nutritional intakes were assessed using a 3-day dietary record and fasting venous blood samples were collected. Serum EPA/DHA concentrations, the EPA/arachidonic acid (ARA) ratio, EPA/DHA intakes, and fish/meat intakes were examined in tertiles as indicator variables, and hazard ratios (HR) were calculated to compare the risk of death across tertiles controlling for sex, age, body mass index, smoking status, alcohol drinking, physical activity, education, employment, and history of diseases. During follow-up (mean 11.7 years), 422 subjects (40.4%) died. The multivariate-adjusted HR for all-cause mortality in subjects in the highest tertile of serum DHA and EPA/ARA ratio was 0.73 (95% confidence intervals (CI): 0.53-0.99) and 0.71 (95% CI: 0.53-0.96) compared with subjects in the lowest tertile, respectively (trend p < 0.05). There were no significant associations between mortality and serum EPA/ARA and DHA/EPA intakes. An increased serum DHA level or EPA/ARA ratio might be recommended for longevity to Japanese community dwellers.
KEYWORDS:
DHA; EPA; Japanese; fish; meat; mortality; serum

Influenza vaccination in the elderly: 25 years follow-up of a randomized controlled trial. No impact on long-term mortality.
Verhees RAF, Thijs C, Ambergen T, Dinant GJ, Knottnerus JA.
PLoS One. 2019 May 23;14(5):e0216983. doi: 10.1371/journal.pone.0216983. eCollection 2019.
PMID: 31120943
https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0216983&type=printable
Abstract
Influenza vaccination is proven effective in preventing influenza. However, long-term effects on mortality have never been supported by direct evidence. In this study we assessed the long-term outcome of influenza vaccination on mortality in the elderly by conducting a 25-year follow-up study of a RCT on the efficacy of influenza vaccination as baseline. The RCT had been conducted in the Netherlands 5 years before vaccination was recommended for those aged >65 and 17 years before recommending it for those aged >60. The RCT included 1838 community-dwelling elderly aged ≥ 60 that had received an intramuscular injection with the inactivated quadrivalent influenza vaccine (n = 927) or placebo (n = 911) during the 1991/1992 winter. In our follow-up study, outcomes included all-cause mortality, influenza-related mortality and seasonal mortality. Unadjusted and adjusted hazard ratios (HRs) were estimated by Cox regression and sub-hazard ratios (SHRs) by competing risk models. Secondary analyses included subgroup analyses by age and disease status. The vital status up to January 1, 2017 was provided in 1800/1838 (98%) of the cases. Single influenza vaccination did not reduce all-cause mortality when compared to placebo (adjusted HR 0.95, 95% CI 0.85-1.05). Also, no differences between vaccination and placebo group were shown for underlying causes of death or seasonal mortality. In those aged 60-64, median survival increased with 20.1 months (95% CI 2.4-37.9), although no effects on all-cause mortality (adjusted HR 0.86, 95% CI 0.72-1.03) could be demonstrated in survival analysis. In conclusion, this study did not demonstrate a statistically significant effect following single influenza vaccination on long-term mortality in community-dwelling elderly in general. We propose researchers designing future studies on influenza vaccination in the elderly to fit these studies for longer-term follow-up, and suggest age-group comparisons in observational research.

Association of vitamin K with cardiovascular events and all-cause mortality: a systematic review and meta-analysis.
Chen HG, Sheng LT, Zhang YB, Cao AL, Lai YW, Kunutsor SK, Jiang L, Pan A.
Eur J Nutr. 2019 May 22. doi: 10.1007/s00394-019-01998-3. [Epub ahead of print] Review.
PMID: 31119401
Abstract
PURPOSE:
We conducted a meta-analysis to systematically assess the prospective association between vitamin K and cardiovascular disease (CVD) events and all-cause mortality.
METHODS:
We searched PubMed and EMBASE through January 2019 for prospective studies that reported the association of vitamin K (assessed by dietary intake or circulating concentration) with CVD events [including total CVD, CVD mortality, total coronary heart disease (CHD), fatal CHD, nonfatal myocardial infarction (MI), and stroke] and all-cause mortality. Multivariable-adjusted hazard ratios (HRs) comparing top versus bottom tertiles of vitamin K were combined using random-effects meta-analysis.
RESULTS:
Twenty-one articles were included with 222,592 participants. A significant association was found between dietary phylloquinone and total CHD (pooled HR 0.92; 95% CI 0.84, 0.99; I2 = 0%; four studies), as well as menaquinone and total CHD (0.70; 95% CI 0.53, 0.93; I2 = 32.1%; two studies). No significant association was observed between dietary vitamin K and all-cause mortality, CVD mortality, or stroke. Elevated plasma desphospho-uncarboxylated MGP (dp-ucMGP), a marker of vitamin K deficiency, was associated with an increased risk of all-cause mortality (1.84; 95% CI 1.48, 2.28; I2 = 16.8%; five studies) and CVD mortality (1.96; 95% CI 1.47, 2.61; I2 = 0%; two studies). No significant association was observed between circulating total osteocalcin and all-cause mortality or total CVD.
CONCLUSIONS:
Our findings showed that higher dietary vitamin K consumption was associated with a moderately lower risk of CHD, and higher plasma dp-ucMGP concentration, but not total circulating osteocalcin, was associated with increased risks of all-cause and CVD mortality. However, causal relations cannot be established because of limited number of available studies, and larger prospective studies and randomized clinical trials are needed to validate the findings.
KEYWORDS:
Cardiovascular disease; Dp-ucMGP; Meta-analysis; Mortality; Osteocalcin; Vitamin K

Cumulative alcohol consumption and stroke risk in men.
Duan Y, Wang A, Wang Y, Wang X, Chen S, Zhao Q, Li X, Wu S, Yang L.
J Neurol. 2019 May 22. doi: 10.1007/s00415-019-09361-6. [Epub ahead of print]
PMID: 31119451
Abstract
BACKGROUNDS:
Views on the relationship between alcohol consumption and stroke risk remain controversial. Moreover, data on cumulative alcohol intake are limited. We examined the potential impact of cumulative alcohol consumption on the risk of total stroke and its subtypes in men.
METHODS:
This prospective study included 23,433 men from the Kailuan Study. Cumulative alcohol consumption was taken as the primary exposure by calculating self-reported alcohol consumption from three consecutive examinations (in 2006, 2008, and 2010). The first occurrence of stroke was confirmed by reviewing medical records from 2010 to 2016. We used Cox proportional hazards regression to analyze the data.
RESULTS:
During the 5.9 ± 0.8 years of follow-up, 678 total strokes were identified, including 595 ischemic stroke (IS), 90 intracerebral hemorrhage and 19 subarachnoid hemorrhage cases. The adjusted hazard ratios (95% confidence intervals) of total stroke for light, moderate and heavy cumulative alcohol consumption were 1.23 (1.01-1.51), 1.49 (1.13-1.97), and 1.50 (1.21-1.86), respectively, compared with those of nondrinkers. The results were similar for IS. Cumulative alcohol consumption was not associated with intracerebral hemorrhage risk (hazard ratio 1.46; 95% confidence interval, 0.74-2.08).
CONCLUSIONS:
Cumulative alcohol consumption is an independent risk factor of total stroke and IS in men in a community-based cohort. Even light alcohol intake increases the risk of total stroke and IS.
KEYWORDS:
Alcohol consumption; Intracerebral hemorrhage; Ischemic stroke; Prospective study; Stroke

[AlPater]

Anti-aging therapies, cognitive impairment and dementia.
Wahl D, Anderson RM, Le Couteur DG.
J Gerontol A Biol Sci Med Sci. 2019 May 24. pii: glz135. doi: 10.1093/gerona/glz135. [Epub ahead of print]
PMID: 31125402
https://sci-hub.tw/10.1093/gerona/glz135
Abstract
Aging is a powerful risk factor for the development of many chronic diseases including dementia. Research based on disease models of dementia have yet to yield effective treatments, therefore it is opportune to consider whether the aging process itself might be a potential therapeutic target for the treatment and prevention of dementia. Numerous cellular and molecular pathways have been implicated in the aging process and compounds that target these processes are being developed to slow aging and delay the onset of age-associated conditions. A few particularly promising therapeutic agents have been shown to influence many of the main hallmarks of aging and increase lifespan in rodents. Here we discuss the evidence that some of these anti-aging compounds may beneficially impact brain aging and thereby lower the risk for dementia.
KEYWORDS:
Brain aging; caloric restriction; cognition; health; lifespan extension

The effect of complete caloric intake restriction on human body odour quality.
Fialová J, Hoffmann R, Roberts SC, Havlíček J.
Physiol Behav. 2019 May 23:112554. doi: 10.1016/j.physbeh.2019.05.015. [Epub ahead of print]
PMID: 31130296
Abstract
Previous studies on various vertebrates have shown that quantity and quality of food intake affect odour attractiveness as perceived by potential mates. In humans, the quality of body odour is similarly affected by ingested foods, such as by variation in meat and garlic intake. Nevertheless, it is not known whether quantity of food has an impact on human body odour attractiveness. Thus, here we tested how 48 h of complete caloric intake restriction affects the hedonic quality of human axillary odour. Odour samples (cotton pads fixed in both armpits and worn for 12 h) were obtained from healthy female donors across three conditions: i) during their habitual food regime; ii) after 48 h of complete caloric intake restriction (drinking water was provided), and iii) 72 h after restoration of caloric intake. Axillary samples were assessed by male raters regarding their pleasantness, attractiveness, femininity, and intensity. We also collected blood samples to assess physiological changes due to dietary restriction (e.g., glucose, sodium, albumin, and triacylglyceride assays) and anthropometric measurements at the same intervals as body odour samples. We found no differences in pleasantness, attractiveness and intensity between the odour samples collected at baseline and during complete caloric intake restriction. Interestingly, we found that body odours were rated more pleasant, more attractive and less intense after restoration of food intake as compared to the baseline and during caloric restriction. Our results suggest that restoration of food intake positively influences hedonic quality of human body odour which might thus provide cues to current fitness status and metabolic efficiency.
KEYWORDS:
Affective states; BMI; Diet; Fasting; Olfaction; Smell

Obesity May Accelerate the Aging Process.
Salvestrini V, Sell C, Lorenzini A.
Front Endocrinol (Lausanne). 2019 May 3;10:266. doi: 10.3389/fendo.2019.00266. eCollection 2019. Review.
PMID: 31130916
https://sci-hub.tw/10.3389/fendo.2019.00266
Abstract
Lines of evidence from several studies have shown that increases in life expectancy are now accompanied by increased disability rate. The expanded lifespan of the aging population imposes a challenge on the continuous increase of chronic disease. The prevalence of overweight and obesity is increasing at an alarming rate in many parts of the world. Further to increasing the onset of metabolic imbalances, obesity leads to reduced life span and affects cellular and molecular processes in a fashion resembling aging. Nine key hallmarks of the aging process have been proposed. In this review, we will review these hallmarks and discuss pathophysiological changes that occur with obesity, that are similar to or contribute to those that occur during aging. We present and discuss the idea that obesity, in addition to having disease-specific effects, may accelerate the rate of aging affecting all aspects of physiology and thus shortening life span and health span.
KEYWORDS:
aging; aging hallmarks; caloric restriction; obesity; overweight

Time-restricted feeding improves adaptation to chronically alternating light-dark cycles.
Schilperoort M, van den Berg R, Dollé MET, van Oostrom CTM, Wagner K, Tambyrajah LL, Wackers P, Deboer T, Hulsegge G, Proper KI, van Steeg H, Roenneberg T, Biermasz NR, Rensen PCN, Kooijman S, van Kerkhof LWM.
Sci Rep. 2019 May 27;9(1):7874. doi: 10.1038/s41598-019-44398-7.
PMID: 31133707
https://www.nature.com/articles/s41598-019-44398-7.pdf
Abstract
Disturbance of the circadian clock has been associated with increased risk of cardio-metabolic disorders. Previous studies showed that optimal timing of food intake can improve metabolic health. We hypothesized that time-restricted feeding could be a strategy to minimize long term adverse metabolic health effects of shift work and jetlag. In this study, we exposed female FVB mice to weekly alternating light-dark cycles (i.e. 12 h shifts) combined with ad libitum feeding, dark phase feeding or feeding at a fixed clock time, in the original dark phase. In contrast to our expectations, long-term disturbance of the circadian clock had only modest effects on metabolic parameters. Mice fed at a fixed time showed a delayed adaptation compared to ad libitum fed animals, in terms of the similarity in 24 h rhythm of core body temperature, in weeks when food was only available in the light phase. This was accompanied by increased plasma triglyceride levels and decreased energy expenditure, indicating a less favorable metabolic state. On the other hand, dark phase feeding accelerated adaptation of core body temperature and activity rhythms, however, did not improve the metabolic state of animals compared to ad libitum feeding. Taken together, restricting food intake to the active dark phase enhanced adaptation to shifts in the light-dark schedule, without significantly affecting metabolic parameters.

Molecular Pathways Mediating Immunosuppression in Response to Prolonged Intensive Physical Training, Low-Energy Availability, and Intensive Weight Loss.
Sarin HV, Gudelj I, Honkanen J, Ihalainen JK, Vuorela A, Lee JH, Jin Z, Terwilliger JD, Isola V, Ahtiainen JP, Häkkinen K, Jurić J, Lauc G, Kristiansson K, Hulmi JJ, Perola M.
Front Immunol. 2019 May 3;10:907. doi: 10.3389/fimmu.2019.00907. eCollection 2019.
PMID: 31134054
[pdf availed free from Pubmed site.]
Abstract
Exercise and exercise-induced weight loss have a beneficial effect on overall health, including positive effects on molecular pathways associated with immune function, especially in overweight individuals. The main aim of our study was to assess how energy deprivation (i.e., "semi-starvation") leading to substantial fat mass loss affects the immune system and immunosuppression in previously normal weight individuals. Thus, to address this hypothesis, we applied a high-throughput systems biology approach to better characterize potential key pathways associated with immune system modulation during intensive weight loss and subsequent weight regain. We examined 42 healthy female physique athletes (age 27.5 ± 4.0 years, body mass index 23.4 ± 1.7 kg/m2) volunteered into either a diet group (n = 25) or a control group (n = 17). For the diet group, the energy intake was reduced and exercise levels were increased to induce loss of fat mass that was subsequently regained during a recovery period. The control group was instructed to maintain their typical lifestyle, exercise levels, and energy intake at a constant level. For quantification of systems biology markers, fasting blood samples were drawn at three time points: baseline (PRE), at the end of the weight loss period (MID 21.1 ± 3.1 weeks after PRE), and at the end of the weight regain period (POST 18.4 ± 2.9 weeks after MID). In contrast to the control group, the diet group showed significant (false discovery rate <0.05) alteration of all measured immune function parameters-white blood cells (WBCs), immunoglobulin G glycome, leukocyte transcriptome, and cytokine profile. Integrative omics suggested effects on multiple levels of immune system as dysregulated hematopoiesis, suppressed immune cell proliferation, attenuated systemic inflammation, and loss of immune cell function by reduced antibody and chemokine secretion was implied after intense weight loss. During the weight regain period, the majority of the measured immune system parameters returned back to the baseline. In summary, this study elucidated a number of molecular pathways presumably explaining immunosuppression in individuals going through prolonged periods of intense training with low-energy availability. Our findings also reinforce the perception that the way in which weight loss is achieved (i.e., dietary restriction, exercise, or both) has a distinct effect on how the immune system is modulated.
KEYWORDS:
bioinformatics; immunosuppression; low energy availability; physical training; weight loss

Aging, lifestyle and dementia.
Wahl D, Solon-Biet SM, Cogger VC, Fontana L, Simpson SJ, Le Couteur DG, Ribeiro RV.
Neurobiol Dis. 2019 May 25:104481. doi: 10.1016/j.nbd.2019.104481. [Epub ahead of print] Review.
PMID: 31136814
https://sci-hub.tw/10.1016/j.nbd.2019.104481
Abstract
Aging is the greatest risk factor for most diseases including cancer, cardiovascular disorders, and neurodegenerative disease. Several interventions can improve metabolic health with emerging evidence suggesting that these may also be effective for brain health. The most robust interventions are non-pharmacological and include limiting calorie or protein intake, aerobic exercise, or environmental enrichment. In humans, dietary patterns including the Mediterranean, Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) and Okinawan diets are associated with improved age-related health and may reduce neurodegenerative disease including dementia. Rapamycin, metformin and resveratrol act on nutrient sensing pathways and improve cardiometabolic health and decrease the risk for age-associated disease. There is some evidence that they may reduce the risk for dementia in rodents. There is a growing recognition that improving metabolic function may be an effective way to optimize brain health during aging.
KEYWORDS:
Aging; Alzheimer's disease; Calorie restriction; Dementia; Metabolic health

Risk Factors for Development of Canine and Human Osteosarcoma: A Comparative Review.
Makielski KM, Mills LJ, Sarver AL, Henson MS, Spector LG, Naik S, Modiano JF.
Vet Sci. 2019 May 25;6(2). pii: E48. doi: 10.3390/vetsci6020048. Review.
PMID: 31130627
[pdf aviled free from Pubmed site.]
Abstract
Osteosarcoma is the most common primary tumor of bone. Osteosarcomas are rare in humans, but occur more commonly in dogs. A comparative approach to studying osteosarcoma has highlighted many clinical and biologic aspects of the disease that are similar between dogs and humans; however, important species-specific differences are becoming increasingly recognized. In this review, we describe risk factors for the development of osteosarcoma in dogs and humans, including height and body size, genetics, and conditions that increase turnover of bone-forming cells, underscoring the concept that stochastic mutational events associated with cellular replication are likely to be the major molecular drivers of this disease. We also discuss adaptive, cancer-protective traits that have evolved in large, long-lived mammals, and how increasing size and longevity in the absence of natural selection can account for the elevated bone cancer risk in modern domestic dogs.
KEYWORDS:
bone cancer; comparative oncology; dog; genetics; human; osteosarcoma; pediatric; risk factors

[AlPater]

Proximate determinants of particulate matter (PM2.5) emission, mortality and life expectancy in Europe, Central Asia, Australia, Canada and the US.
Sarkodie SA, Strezov V, Jiang Y, Evans T.
Sci Total Environ. 2019 May 21;683:489-497. doi: 10.1016/j.scitotenv.2019.05.278. [Epub ahead of print]
PMID: 31141750
Abstract
BACKGROUND:
The growing concern with environmental related impacts on mortality and morbidity means that the conceptual framework of environment-health-economic policy nexus is salient in the global debate on air pollution.
OBJECTIVES:
With time series data spanning 2000-2016, this study explored the proximate determinants of ambient air pollution, mortality, and life expectancy in North America, Europe & Central Asia, and East Asia & Pacific regions.
METHODS:
The study applied historical data on urban population, total pollution, energy consumption, GDP per capita, life expectancy, mortality rate and industrial PM2.5 emissions to develop six parsimonious models using the generalized least squares (GLS) random-effects model estimation with first-order autoregressive [AR(1)] disturbance across 54 countries.
RESULTS:
An increase in income level by 1% declined mortality rate by 0.01% and increased longevity by ~0.02% (95% Confidence Interval [CI]) in the long-run. An increase in industrial PM2.5 emissions per capita by 1% decreased life expectancy by 0.004% and mortality rate by 0.02% (95% CI). Intensification of energy consumption and its related services by 1% were found to increase industrial PM2.5 emissions by 0.42-0.45% (95% CI). An inversed-U shaped curve between PM2.5 emissions per capita and income levels was found at a turning point of US$ 48,061. The validity of an environmental Kuznets curve hypothesis between ambient air pollution and urbanization was confirmed, while a rapid increase in population had a significant positive impact on ambient air pollution.
CONCLUSION:
Ambient air pollution contributes significantly in reducing life expectancy and increasing mortality. However, sustained economic development, along with energy efficiency, and sustainable urban settlement planning and management are potential options for reducing ambient air pollution while improving quality of life and environmental sustainability.
KEYWORDS:
Air pollution; EKC hypothesis; Energy consumption; Environmental sustainability; Mortality rate; Panel data

Telomerase gene therapy ameliorates the effects of neurodegeneration associated to short telomeres in mice.
Whittemore K, Derevyanko A, Martinez P, Serrano R, Pumarola M, Bosch F, Blasco MA.
Aging (Albany NY). 2019 May 28. doi: 10.18632/aging.101982. [Epub ahead of print]
PMID: 31140977
Abstract
Neurodegenerative diseases associated with old age such as Alzheimer's disease present major problems for society, and they currently have no cure. The telomere protective caps at the ends of chromosomes shorten with age, and when they become critically short, they can induce a persistent DNA damage response at chromosome ends, triggering secondary cellular responses such as cell death and cellular senescence. Mice and humans with very short telomeres owing to telomerase deficiencies have an earlier onset of pathologies associated with loss of the regenerative capacity of tissues. However, the effects of short telomeres in very low proliferative tissues such as the brain have not been thoroughly investigated. Here, we describe a mouse model of neurodegeneration owing to presence of short telomeres in the brain as the consequence of telomerase deficiency. Interestingly, we find similar signs of neurodegeneration in very old mice as the consequence of physiological mouse aging. Next, we demonstrate that delivery of telomerase gene therapy to the brain of these mice results in amelioration of some of these neurodegeneration phenotypes. These findings suggest that short telomeres contribute to neurodegeneration diseases with aging and that telomerase activation may have a therapeutic value in these diseases.
KEYWORDS:
TERT; gene therapy; neurodegeneration; telomerase

Association Between Life Purpose and Mortality Among US Adults Older Than 50 Years.
Alimujiang A, Wiensch A, Boss J, Fleischer NL, Mondul AM, McLean K, Mukherjee B, Pearce CL.
JAMA Netw Open. 2019 May 3;2(5):e194270. doi: 10.1001/jamanetworkopen.2019.4270.
PMID: 31125099
[pdf availed free from Pubmed site.]
Abstract
IMPORTANCE:
A growing body of literature suggests that having a strong sense of purpose in life leads to improvements in both physical and mental health and enhances overall quality of life. There are interventions available to influence life purpose; thus, understanding the association of life purpose with mortality is critical.
OBJECTIVE:
To evaluate whether an association exists between life purpose and all-cause or cause-specific mortality among older adults in the United States.
DESIGN, SETTING, AND PARTICIPANTS:
The Health and Retirement Study (HRS) is a national cohort study of US adults older than 50 years. Adults between the ages of 51 to 61 were enrolled in the HRS, and their spouses or partners were enrolled regardless of age. Initially, individuals born between 1931 and 1941 were enrolled starting in 1992, but subsequent cohort enrichment was carried out. The present prospective cohort study sample was drawn from 8419 HRS participants who were older than 50 years and who had filled out a psychological questionnaire during the HRS 2006 interview period. Of these, 1142 nonresponders with incomplete life purpose data, 163 respondents with missing sample weights, 81 participants lost to follow-up, 1 participant with an incorrect survival time, and 47 participants with missing information on covariates were excluded. The final sample for analysis was 6985 individuals. Data analyses were conducted between June 5, 2018, and April 22, 2019.
EXPOSURES:
Purpose in life was assessed for the 2006 interview period with a 7-item questionnaire from the modified Ryff and Keyes Scales of Psychological Well-being evaluation using a Likert scale ranging from 1 to 6, with higher scores indicating greater purpose in life; for all-cause and cause-specific mortality analyses, 5 categories of life purpose scores were used (1.00-2.99, 3.00-3.99, 4.00-4.99, 5.00-5.99, and 6.00).
MAIN OUTCOMES AND MEASURES:
All-cause and cause-specific mortality were assessed between 2006 and 2010. Weighted Cox proportional hazards models were used to evaluate life purpose and mortality.
RESULTS:
Of 6985 individuals included in the analysis, 4016 (57.5%) were women, the mean (SD) age of all participants was 68.6 (9.8) years, and the mean (SD) survival time for decedents was 31.21 (15.42) months (range, 1.00-71.00 months). Life purpose was significantly associated with all-cause mortality in the HRS (hazard ratio, 2.43; 95% CI, 1.57-3.75, comparing those in the lowest life purpose category with those in the highest life purpose category). Some significant cause-specific mortality associations with life purpose were also observed (heart, circulatory, and blood conditions: hazard ratio, 2.66; 95% CI, 1.62-4.38).
CONCLUSIONS AND RELEVANCE:
This study's results indicated that stronger purpose in life was associated with decreased mortality. Purposeful living may have health benefits. Future research should focus on evaluating the association of life purpose interventions with health outcomes, including mortality. In addition, understanding potential biological mechanisms through which life purpose may influence health outcomes would be valuable.

[AlPater]

Changes in Anxiety and Depression Traits Induced by Energy Restriction: Predictive Value of the Baseline Status.
Rodriguez-Lozada C, Cuervo M, Cuevas-Sierra A, Goni L, Riezu-Boj JI, Navas-Carretero S, Milagro FI, Martinez JA.
Nutrients. 2019 May 28;11(6). pii: E1206. doi: 10.3390/nu11061206.
PMID: 31141954
[pdf availed from PMID site.]
Abstract
Current evidence proposes diet quality as a modifiable risk factor for mental or emotional impairments. However, additional studies are required to investigate the effect of dietary patterns and weight loss on improving psychological symptoms. The aim of this investigation was to evaluate the effect of energy-restriction, prescribed to overweight and obese participants, on anxiety and depression symptoms, as well as the potential predictive value of some baseline psychological features on weight loss. Overweight and obese participants (n = 305) were randomly assigned for 16 weeks to two hypocaloric diets with different macronutrient distribution: a moderately high-protein (MHP) diet and a low-fat (LF) diet. Anthropometrical, clinical, psychological, and lifestyle characteristics were assessed at baseline and at the end of the intervention. The nutritional intervention evidenced that weight loss has a beneficial effect on trait anxiety score in women (β = 0.24, p = 0.03), depression score in all population (β = 0.15, p = 0.02), particularly in women (β = 0.22, p = 0.03) and in subjects who followed the LF diet (β = 0.22, p = 0.04). Moreover, weight loss could be predicted by anxiety status at baseline, mainly in women and in those who were prescribed a LF diet. This trial suggests that weight loss triggers an improvement in psychological traits, and that anxiety symptoms could predict those volunteers that benefit most from a balanced calorie-restricted intervention, which will contribute to individualized precision nutrition.
KEYWORDS:
anxiety; depression; hypocaloric diet; macronutrient distribution; overweight; weight loss

The Association Between Low Serum Cholesterol and Non-Cardiovascular Mortality among Italian Males and Females: A Nine- Year Prospective Cohort Ctudy
Taravatmanesh S, Parsa N, Trevisan M, Zaheri PM.
Asian Pac J Cancer Prev. 2019 May 25;20(5):1361-1368.
PMID: 31127892 Free Article
http://journal.waocp.org/article_86821_65e75b4e76ce96e879c3fde1fa7e9b1a.pdf
Abstract
BACKGROUND:
No study to date provides evidence suggesting that lower cholesterol is associated with excess death in non-cardiovascular disease (NCVD). This study aimed to determine the association between low cholesterol level and NCVD mortality.
METHODS:
A nine-year cohort study was conducted on 3,079 male and 26,005 female Italians aged 20-69 years old. The Cox proportional hazard models implied a hazard ratio with 95% confidence interval for association.
RESULTS:
Among males, there were significant inverse associations between the lowest cholesterol decile (< 160mg/dl) hazard ratio and all-cause deaths and non-cardiovascular deaths, 1.50 (1.19-1.89) and 2.06 (1.54-2.74), respectively. Among females, there was a significant inverse association of lowest and fourth cholesterol deciles, 1.53 (1.01-2.34); 1.52 (1.06-2.18) hazard ratio for all-cause deaths and risk for non-cardiovascular deaths in the same deciles 1.52 (0.91-2.50); 1.78 (1.16-2.71), respectively. Remarkably, in depth analysis for NCVD, found significant inverse associations hazard of cholesterol <160 mg/dl for cancer, non-cancer liver dysfunction (NCLD), other non-cancer-non- CVD in males and only NCLD death was significant in females.
CONCLUSION:
Among males, there were significant inverse hazard associations between the lowest cholesterol decile and all-cause and non-CVD deaths . Among females, there were significant inverse hazard associations of lowest and fourth cholesterol decile for all-cause and also risk first and fourth deciles for non-CVD mortality.
KEYWORDS:
Low cholesterol; non-cardiovascular; mortality

Trajectories of Blood Lipid Concentrations Over the Adult Life Course and Risk of Cardiovascular Disease and All-Cause Mortality: Observations From the Framingham Study Over 35 Years.
Duncan MS, Vasan RS, Xanthakis V.
J Am Heart Assoc. 2019 Jun 4;8(11):e011433. doi: 10.1161/JAHA.118.011433. Epub 2019 May 29.
PMID: 31137992 Free Article
https://www.ahajournals.org/doi/pdf/10.1161/JAHA.118.011433
Abstract
Background Elevated total cholesterol ( TC ), low-density lipoprotein cholesterol ( LDL -C), triglycerides, and non-high-density lipoprotein cholesterol (non- HDL -C) and low high-density lipoprotein cholesterol ( HDL -C) concentrations correlate with atherosclerotic cardiovascular disease ( ASCVD ) and mortality. Therefore, understanding how lipid trajectories throughout adulthood impact ASCVD and mortality risk is essential. Methods and Results We investigated 3875 Framingham Offspring participants (54% women, mean age 48 years) attending ≥1 examination between 1979 and 2014. We evaluated longitudinal correlates of each lipid subtype using mixed-effects models. Next, we clustered individuals into trajectories through group-based modeling. Thereafter, we assessed the prospective association of lipid trajectories with ASCVD and mortality. Male sex, greater body mass index, and smoking correlated with higher TC , LDL -C, triglycerides, non- HDL -C, and lower HDL -C concentrations. We identified 5 TC , HDL -C, and LDL -C trajectories, and 4 triglycerides and non- HDL -C trajectories. Upon follow-up (median 8.2 years; 199 ASCVD events; 256 deaths), elevated TC (>240 mg/ dL ), LDL -C (>155 mg/ dL ), or non- HDL -C (>180 mg/ dL ) concentrations conferred >2.25-fold ASCVD and mortality risk compared with concentrations <165 mg/ dL , <90 mg/ dL , and <115 mg/ dL , respectively ([ TC hazard ratio ( HR )ASCVD=4.17, 95% CI 1.94-8.99; TC HR death=2.47, 95% CI 1.28-4.76] [ LDL -C HRASCVD=5.09, 95% CI 1.54-16.85; LDL -C HR death=4.04, 95% CI 1.84-8.89] [non- HDL -C HRASCVD=4.60, 95% CI 1.98-10.70; LDL -C HR death=3.74, 95% CI 2.03-6.88]). Consistent HDL -C concentrations <40 mg/ dL were associated with greater ASCVD and mortality risk than concentrations >70 mg/ dL (HRASCVD=3.81, 95% CI 2.04-7.15; HR death=2.88, 95% CI 1.70-4.89). Triglycerides trajectories were unassociated with outcomes. Conclusions Using a longitudinal modeling technique, we demonstrated that unfavorable lipid trajectories over 35 years confer higher ASCVD and mortality risk later in life.
KEYWORDS:
cardiovascular disease; life‐course; lipids; longitudinal; trajectories

Association of Step Volume and Intensity With All-Cause Mortality in Older Women.
Lee IM, Shiroma EJ, Kamada M, Bassett DR, Matthews CE, Buring JE.
JAMA Intern Med. 2019 May 29. doi: 10.1001/jamainternmed.2019.0899. [Epub ahead of print]
PMID: 31141585
Abstract
IMPORTANCE:
A goal of 10 000 steps/d is commonly believed by the public to be necessary for health, but this number has limited scientific basis. Additionally, it is unknown whether greater stepping intensity is associated with health benefits, independent of steps taken per day.
OBJECTIVE:
To examine associations of number of steps per day and stepping intensity with all-cause mortality.
DESIGN, SETTING, AND PARTICIPANTS:
This prospective cohort study included 18 289 US women from the Women's Health Study who agreed to participate by wearing an accelerometer during waking hours for 7 days between 2011 and 2015. A total of 17 708 women wore and returned their devices; data were downloaded successfully from 17 466 devices. Of these women, 16 741 were compliant wearers (≥10 h/d of wear on ≥4 days) and included in the analyses, which took place between 2018 and 2019.
EXPOSURES:
Steps per day and several measures of stepping intensity (ie, peak 1-minute cadence; peak 30-minute cadence; maximum 5-minute cadence; time spent at a stepping rate of ≥40 steps/min, reflecting purposeful steps).
MAIN OUTCOMES AND MEASURES:
All-cause mortality.
RESULTS:
Of the 16 741 women who met inclusion criteria, the mean (SD) age was 72.0 (5.7) years. Mean step count was 5499 per day, with 51.4%, 45.5%, and 3.1% of time spent at 0, 1 to 39 (incidental steps), and 40 steps/min or greater (purposeful steps), respectively. During a mean follow-up of 4.3 years, 504 women died. Median steps per day across low-to-high quartiles of distribution were 2718, 4363, 5905, and 8442, respectively. The corresponding quartile hazard ratios (HRs) associated with mortality and adjusted for potential confounders were 1.00 (reference), 0.59 (95% CI, 0.47-0.75), 0.54 (95% CI, 0.41-0.72), and 0.42 (95% CI, 0.30-0.60), respectively (P < .01). In spline analysis, HRs were observed to decline progressively with higher mean steps per day until approximately 7500 steps/d, after which they leveled. For measures of stepping intensity, higher intensities were associated with significantly lower mortality rates; however, after adjusting for steps per day, all associations were attenuated, and most were no longer significant (highest vs lowest quartile for peak 1-minute cadence, HR = 0.87 [95% CI, 0.68-1.11]; peak 30-minute cadence, HR = 0.86 [95% CI, 0.65-1.13]; maximum 5-minute cadence, HR = 0.80 [95% CI, 0.62-1.05]; and time spent at a stepping rate of ≥40 steps/min, HR = 1.27 [95% CI, 0.96-1.68]; P > .05).
CONCLUSIONS AND RELEVANCE:
Among older women, as few as approximately 4400 steps/d was significantly related to lower mortality rates compared with approximately 2700 steps/d. With more steps per day, mortality rates progressively decreased before leveling at approximately 7500 steps/d. Stepping intensity was not clearly related to lower mortality rates after accounting for total steps per day.

Isocaloric Substitution of Dietary Carbohydrate Intake with Fat Intake and MRI-Determined Total Volumes of Visceral, Subcutaneous and Hepatic Fat Content in Middle-Aged Adults.
Meisinger C, Rospleszcz S, Wintermeyer E, Lorbeer R, Thorand B, Bamberg F, Peters A, Schlett CL, Linseisen J.
Nutrients. 2019 May 23;11(5). pii: E1151. doi: 10.3390/nu11051151.
PMID: 31126078 Free Article
[pdf availed from PMID site.]
Abstract
The present study investigated the association of carbohydrate intake and isocaloric substitution with different types of fat with visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and hepatic fat content as determined by magnetic resonance imaging (MRI). Data from 283 participants (mean age 56.1 ± 9.0 years) from the MRI sub study of the KORA FF4 study were included. VAT, SAT and total body fat were quantified by a volume-interpolated VIBE-T1w-Dixon MR sequence. Hepatic fat content was determined as the proton density fat-fraction (PDFF) derived from multiecho-T1w MR sequence. Dietary intake was estimated using information provided by two different instruments, that is, repeated 24-h food lists and a food frequency questionnaire. Replacing total carbohydrates with an isoenergetic amount of total fat was significantly positively associated with VAT and hepatic fat, while there was no significant association with SAT. The multivariable adjusted β-coefficient for replacing 5% of total energy (5E%) carbohydrates with total fat was 0.42 L (95% CI: 0.04, 0.79) for VAT. A substitution in total fat intake by 5E% was associated with a significant increase in liver fat content by 23% (p-value 0.004). If reproduced in prospective studies, such findings would strongly argue for limiting dietary fat intake.
KEYWORDS:
MRI; body fat compartments; diet; fat intake; hepatic fat content; visceral adipose tissue

Dietary Intakes of Branched Chain Amino Acids and the Incidence of Hypertension: A Population-Based Prospective Cohort Study.
Mirmiran P, Teymoori F, Asghari G, Azizi F.
Arch Iran Med. 2019 Apr 1;22(4):182-188.
PMID: 31126176 Free Article
Abstract
BACKGROUND:
Dietary amino acids have been associated with blood pressure (BP) in previous studies; we conducted this study to examine the association between dietary branched chain amino acids (BCAAs) and the incidence of hypertension among participants of the Tehran Lipid and Glucose Study (TLGS).
METHODS:
Analyses were conducted on 4,288 participants aged 20-70 years, who were free of hypertension at baseline (2008- 2011) and were followed for 3 years (2011-2014) to ascertain incident hypertension. Dietary intakes of BCAAs including, valine, leucine, and isoleucine were collected at baseline using the food frequency questionnaire (FFQ). Odds ratio (OR) of hypertension were determined by logistic regression across quartiles of BCAAs, adjusted for sex, age, smoking status, physical activity, body mass index (BMI), diabetes, and some dietary factors.
RESULTS:
The mean ± standard deviation for age and BMI of participants (41.9% men) were 39.7 ± 12.8 years and 26.9 ± 4.6 kg/ m2 , respectively. The median intakes of total BCAAs, valine, leucine, and isoleucine was 17.9, 5.5, 7.8, and 4.5 percentage of total amino acids intake, respectively. We documented 429 (10%) hypertension incident cases. The multivariable adjusted OR for the highest vs lowest quartiles of BCAAs was 1.54 (95% confidence interval (CI):1.03-2.32; P for trend = 0.05); furthermore, the OR (95% CI) of hypertension for the highest vs the lowest quartile of valine was 1.61 (1.10-2.36; P for trend = 0.009) in the fully adjusted model. However, we found no significant association between leucine and isoleucine with incidence of hypertension.
CONCLUSION:
Findings indicated that higher BCAA intake, in particular valine, is associated with higher risk of incident hypertension.
KEYWORDS:
Branched chain amino acids; Hypertension; Isoleucine; Leucine; Valine

[AlPater]

Circulating sex hormone levels and colorectal cancer risk in Japanese postmenopausal women: The JPHC nested case-control study.
Mori N, Sawada N, Iwasaki M, Yamaji T, Goto A, Shimazu T, Inoue M, Murphy N, Gunter MJ, Tsugane S.
Int J Cancer. 2019 May 27. doi: 10.1002/ijc.32431. [Epub ahead of print]
PMID: 31131883
Abstract
Previous epidemiological studies evaluated endogenous sex hormone levels and colorectal cancer (CRC) risk have yielded inconsistent results. Also, it is unknown if consumption of dietary isoflavones may influence the endogenous sex hormones and CRC relationships. We conducted a nested-case control study within the JPHC Study Cohort II wherein 11,644 women provided blood samples at the 5-year follow-up survey. We selected two matched controls for each case from the cohort (185 CRC cases and 361 controls). Multivariable conditional logistic regression was used to estimate odds ratios (ORs), 95% confidence intervals (CIs) for the association between circulating sex hormone levels and CRC risk. Comparing extreme tertiles, circulating testosterone levels were positively associated with CRC risk (OR = 2.10, 95% CI = 1.11 to 3.99, P for trend = 0.03). Levels of estradiol, SHBG, and progesterone were not associated with CRC risk. In a subgroup analysis by dietary isoflavone intake, SHBG levels were positively associated with CRC risk among those with low total isoflavone intake (P for trend = 0.03), with a statistically non-significant inverse association among those with high total isoflavone intake (P for trend = 0.22) (P for interaction = 0.002). Endogenous levels of testosterone were positively associated with CRC among postmenopausal women. The association of endogenous SHBG with CRC development may be altered by the level of dietary isoflavone intake.
KEYWORDS:
colorectal cancer; isoflavone; postmenopause; sex hormone binding globulin; testosterone

Women in LOVe: Lacto-Ovo-Vegetarian Diet Rich in Omega-3 Improves Vasomotor Symptoms in Postmenopausal Women. An Exploratory Randomized Controlled Trial.
Ornella R, Iris Z, Nicola V, Maria CA, Rosa R, Rosa I, Gioacchino L, Maria N, Valeria T, Valentina N, Giampiero L, Vito G, Rossella D, Fabio F, Raffaella L, Anna M, Costanza MRC, Tiziana D, Nicola G, Aurelia IP, Gabriella CM.
Endocr Metab Immune Disord Drug Targets. 2019 May 27. doi: 10.2174/1871530319666190528101532. [Epub ahead of print]
PMID: 31132980
Abstract
OBJECTIVES:
In the postmenopausal period, most women suffer vasomotor symptoms (VMS). It is well known that VMS can worsen the quality of life. Diet seems to play a relevant role in the development of VMS, but the effect of diet on VMS is mainly limited to observational studies, and analyses of nutritional supplements. The aim of this study was thus to determine the efficacy of a lacto-ovo-vegetarian (LOVe) diet rich in omega-3 fatty acids vs. a lacto-ovo-vegetarian diet rich in EVO (extra-virgin olive oil) in reducing VMS frequency in postmenopausal women.
METHODS:
A two-arms (lacto-ovo-vegetarian diet with EVO vs. lacto-ovo-vegetarian diet rich in omega-3) randomized-controlled trial with a follow-up period of 16 weeks. We considered as primary outcome the change in the Kupperman index (follow-up vs. baseline evaluation, reported as Δ) and in its subscales. Secondary outcomes included changes in common anthropometric and bio-humoral measurements.
RESULTS:
Among 54 women randomly assigned to a study group, 40 (mean age 55.1±5.4 years) completed the study and complied with their assigned diet. Women randomized to the omega-3 group (n=18) showed significant improvements, compared to the EVO group (n=22), in Kupperman index (Δ=-11.4±9.8 vs. -5.9±8.2; p=0.045), hot flashes (Δ=-3.3±3.4 vs. -1.3±2.6; p=0.04), and a marginally significant improvement in nervousness (Δ=-1.7±1.7 vs. -0.8±1.5; p=0.07). No significant differences were observed for the secondary outcomes. No relevant side effects were reported.
CONCLUSIONS:
After 16 weeks, a lacto-ovo-vegetarian diet rich in omega-3 reduced VMS frequency in postmenopausal women more than the lacto-ovo-vegetarian diet rich in EVO.
KEYWORDS:
Kupperman index; RCT; diet; lacto-ovo-vegetarian; menopause; omega 3

Dietary intake and cognitive function: evidence from the Bogalusa Heart Study.
Fortune NC, Harville EW, Guralnik JM, Gustat J, Chen W, Qi L, Bazzano LA.
Am J Clin Nutr. 2019 Jun 1;109(6):1656-1663. doi: 10.1093/ajcn/nqz026.
PMID: 31136655
https://sci-hub.tw/10.1093/ajcn/nqz026
Abstract
BACKGROUND:
Dementia and late-life cognitive decline are leading causes of death and disability in the United States. Prevention of these diseases, by maintaining brain health throughout the life course, is essential. Diet and lifestyle changes are the chief strategies aimed at primary prevention for many of the risk factors of cognitive decline.
OBJECTIVE:
The aim of this study was to examine the potential impact of dietary factors on cognitive function.
METHODS:
This prospective cohort study followed 516 young adults through midlife. The Youth/Adolescent Questionnaire was used to collect habitual nutrition data (mean age: 32.03 ± 5.96 y) at baseline. Scores from a neurocognitive battery were used to assess cognitive function (mean age: 49.03 ± 4.86 y) at follow-up and were transformed to z scores. Separate multivariable-adjusted linear regression models were fitted. The trend across quintiles for each dietary variable was assessed.
RESULTS:
Vitamin B-6, whole grains, processed meats, and foods fried at home all displayed significant linear trends in their relation with cognitive function. Dietary intake of vitamin B-6 and whole grains was directly associated with better cognitive function after adjustment for age, race, sex, and total calorie intake (β coefficient from linear regression and SE: 1.755 ± 0.621, P = 0.005, and 0.001 ± 0.000, P = 0.018, respectively). Processed meat and foods fried at home consistently displayed inverse associations with cognitive function across crude and adjusted models (linear trend P values were 0.05 and <0.0001, respectively).
CONCLUSIONS:
Our findings suggest that dietary consumption in young adulthood may affect cognitive function in midlife. Strong associations between dietary intake and cognition were observed in our analysis, but as with all observational studies, the possibility of residual confounding cannot be excluded.
KEYWORDS:
brain health; cognition; cognitive function; diet; nutrition

Endothelial Function is improved by Inducing Microbial Polyamine Production in the Gut: A Randomized Placebo-Controlled Trial.
Matsumoto M, Kitada Y, Naito Y.
Nutrients. 2019 May 27;11(5). pii: E1188. doi: 10.3390/nu11051188.
PMID: 31137855 Free Article
[pdf availed from PMID site.]
Abstract
Recently, it was demonstrated that spermidine-induced autophagy reduces the risk of cardiovascular disease in mice. Intestinal bacteria are a major source of polyamines, including spermidine. We previously reported that the intake of both Bifidobacterium animalis subsp. lactis (Bifal) and arginine (Arg) increases the production of putrescine, a spermidine precursor, in the gut. Here, we investigated the effects of Bifal and Arg consumption on endothelial function in healthy subjects. Healthy individuals with body mass index (BMI) near the maximum value in the "healthy" range (BMI: 25) (n = 44) were provided normal yogurt containing Bifal and Arg (Bifal + Arg YG) or placebo (normal yogurt) for 12 weeks in this randomized, double-blinded, placebo-controlled, parallel-group comparative study. The reactive hyperemia index (RHI), the primary outcome, was measured using endo-peripheral arterial tone (EndoPAT). The change in RHI from week 0 to 12 in the Bifal + Arg YG group was significantly higher than that in the placebo group, indicating that Bifal + Arg YG intake improved endothelial function. At week 12, the concentrations of fecal putrescine and serum putrescine and spermidine in the Bifal + Arg YG group were significantly higher than those in the placebo group. This study suggests that consuming Bifal + Arg YG prevents or reduces the risk of atherosclerosis.
KEYWORDS:
Bifidobacterium animalis subsp. lactis; arginine; autophagy; endothelial function; intestinal microbiome; putrescine; spermidine

Association between vitamin B group supplementation with changes in % flow-mediated dilatation and plasma homocysteine levels: a randomized controlled trial.
Maruyama K, S Eshak E, Kinuta M, Nagao M, Cui R, Imano H, Ohira T, Iso H.
J Clin Biochem Nutr. 2019 May;64(3):243-249. doi: 10.3164/jcbn.17-56. Epub 2019 Mar 7.
PMID: 31138959 Free Article
https://www.jstage.jst.go.jp/article/jcbn/64/3/64_17-56/_pdf
Abstract
There is limited evidence examining the association between B vitamin supplementation and improved endothelial function via lowering plasma homocysteine levels. This study investigated whether low-dose B vitamin supplementation improves endothelial dysfunction in Japanese adults with one or more components of metabolic syndrome. A randomized, controlled, crossover trial, without a washout period or blinding of subjects, was conducted from May-September, 2010. The subjects were 127 Japanese men and women aged 40-65 years who had at least one component of metabolic syndrome without medication. Participants took a supplement drink for two months but were divided into early intervention or later intervention groups. The flow-mediated dilatation, plasma homocysteine level, serum B-vitamins, and vitamin C levels were measured. A significant increase in serum B vitamins and vitamin C levels, and a reduction in plasma homocysteine levels were observed. The mean serum homocysteine level pre- and post-intervention was 9.8 and 8.2 µmol/L in the early intervention group and 10.8 and 7.4 µmol/L in the later intervention group (p<0.01). However, no significant changes in flow-mediated dilatation was found. Low-dose multivitamin supplementation including B vitamins is associated with a significant reduction in plasma homocysteine levels among patients with one or more components of metabolic syndrome.
KEYWORDS:
clinical trial; folate; plasma homocysteine; vitamin B12; vitamin B6

Associations of calcium and dairy product intakes with all-cause, all-cancer, colorectal cancer and CHD mortality among older women in the Iowa Women's Health Study.
Um CY, Prizment A, Hong CP, Lazovich D, Bostick RM.
Br J Nutr. 2019 May;121(10):1188-1200. doi: 10.1017/S000711451900045X. Epub 2019 Mar 5.
PMID: 30834851
Abstract
Ca and dairy product intakes may be inversely associated with all-cause and cause-specific mortality, and non-Ca components of dairy products, such as insulin-like growth factor-1, may be independently associated with mortality. We investigated associations of Ca and dairy product intakes with all-cause, all-cancer, colorectal cancer (CRC) and CHD mortality among 35 221 55- to 69-year-old women in the prospective Iowa Women's Health Study, who were cancer-free in 1986. We assessed diet using a Willett FFQ, and associations using multivariable Cox proportional hazards regression. We estimated residuals from linear regression models of dairy products with dietary Ca to investigate total and specific dairy products independent of their Ca content. Through 2012, 18 687 participants died, including 4665 from cancer (including 574 from CRC) and 3603 from CHD. For those in the highest relative to the lowest quintiles of intake, the multivariable-adjusted hazard ratios (HR) and 95 % CI for total Ca (dietary plus supplemental) were 0·88 (0·83, 0·93; P trend=0·001) for all-cause mortality, 0·91 (0·81, 1·02; P trend=0·34) for all-cancer mortality, 0·60 (0·43, 0·83; P trend=0·002) for CRC mortality and 0·73 (0·64, 0·83; P trend &lt;0·0001) for CHD mortality. The corresponding HR for associations of whole milk, whole milk residuals, and low-/non-fat milk residuals with all-cause mortality were 1·20 (95 % CI 1·13, 1·27), 1·20 (95 % CI 1·13, 1·28) and 0·91 (95 % CI 0·86, 0·96), respectively. These results suggest that Ca may be associated with lower risk of all-cause, CRC and CHD mortality, and that non-Ca components of milk may be independently associated with mortality.
KEYWORDS:
CRC colorectal cancer; HR hazard ratio; ICD International Classification of Diseases; IGF-1 insulin-like growth factor-1; Calcium; Cohort studies; Colorectal cancer; Dairy products; Mortality

[AlPater]

Association between nut consumption and nonalcoholic fatty liver disease in adults.
Zhang S, Fu J, Zhang Q, Liu L, Meng G, Yao Z, Wu H, Bao X, Gu Y, Lu M, Sun S, Wang X, Zhou M, Jia Q, Song K, Xiang H, Wu Y, Niu K.
Liver Int. 2019 Jun 4. doi: 10.1111/liv.14164. [Epub ahead of print]
PMID: 31162803
Abstract
BACKGROUND & AIMS:
Increased nut consumption has been associated with reduced inflammation, insulin resistance, and oxidative stress. Although these factors are closely involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), few studies have focused on the association between nut consumption and NAFLD in the general population. We aimed to investigate the association of nut consumption and NAFLD in an adult population.
METHODS:
A total of 23,915 participants from Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIH) Cohort Study were included in the present study. Information on dietary intake was collected using a validated food frequency questionnaire. Abdominal ultrasonography was applied to diagnose NAFLD. Multivariable logistic regression was used to assess the association of nut consumption with NAFLD.
RESULTS:
After adjusting for sociodemographic, medical, dietary, and lifestyle variables, the odds ratios (95% confidence interval) for NAFLD across categories of nut consumption were 1.00 (reference) for <1 time/week, 0.91 (0.82, 1.02) for 1 time/week, 0.88 (0.76, 1.02) for 2-3 times/week, and 0.80 (0.69, 0.92) for ≥4 times/week (P for trend <0.01). These associations were attenuated but remained significant after further adjustment for blood lipids, glucose, and inflammation markers.
CONCLUSIONS:
Higher nut consumption was significantly associated with lower prevalence of NAFLD. Further prospective studies and randomized trials are required to ascertain the causal association between nut consumption and NAFLD.
KEYWORDS:
NAFLD ; Adults; nonalcoholic fatty liver disease; nuts

Intake of Vegetables and Fruits Through Young Adulthood Is Associated with Better Cognitive Function in Midlife in the US General Population.
Mao X, Chen C, Xun P, Daviglus ML, Steffen LM, Jacobs DR, Van Horn L, Sidney S, Zhu N, Qin B, He K.
J Nutr. 2019 Jun 4. pii: nxz076. doi: 10.1093/jn/nxz076. [Epub ahead of print]
PMID: 31162586
https://sci-hub.tw/https://academic.oup.com/jn/advance-article-abstract/doi/10.1093/jn/nxz076/5510603?redirectedFrom=fulltext
Abstract
BACKGROUND:
Vegetables and fruits (VF) may differentially affect cognitive functions, presumably due to their various nutrient contents, but evidence from epidemiologic studies is limited.
OBJECTIVES:
The aim of this study was to examine the long-term association between VF intakes, including VF subgroups, in young adulthood and cognitive function in midlife.
METHODS:
A biracial cohort of 3231 men and women aged 18-30 y at baseline in 1985-1986 were followed up for 25 y in the Coronary Artery Risk Development in Young Adults Study. Diet was measured at baseline, and in examination years 7 and 20. Cognitive function was assessed at examination year 25 through the use of 3 tests: the Rey Auditory Verbal Learning Test (RAVLT), the Digit Symbol Substitution Test (DSST), and the Stroop test. The mean differences (MDs) with 95% CIs in cognitive scores across intake categories were estimated through the use of the multivariable-adjusted general linear regression model.
RESULTS:
Excluding potatoes, intake of whole vegetables was significantly associated with a better cognitive performance after adjustment for potential confounders in all 3 cognitive tests (quintile 5 compared with quintile 1-RAVLT, MD: 0.33; 95% CI: 0.01, 0.64; P-trend = 0.08; DSST, MD: 2.84; 95% CI: 0.93, 4.75; P-trend < 0.01; Stroop test, MD: -2.87; 95% CI: -4.24, -1.50; P-trend < 0.01]. Similarly, intake of fruits, except fruit juices, was significantly related to a better cognitive performance (quintile 5 compared with quintile 1-DSST, MD: 2.41; 95% CI: 0.70, 4.12; P-trend = 0.03).
CONCLUSIONS:
This study supports the long-term benefits of VF consumption on cognitive performance, except those VF with relatively low fiber content such as potatoes and fruit juices, among the middle-aged US general population.
KEYWORDS:
CARDIA study; cognitive function; dietary fiber; fruits; longitudinal study; vegetables

Dairy, soy, and calcium consumption and risk of cognitive impairment: the Singapore Chinese Health Study.
Talaei M, Feng L, Yuan JM, Pan A, Koh WP.
Eur J Nutr. 2019 Jun 3. doi: 10.1007/s00394-019-02010-8. [Epub ahead of print]
Abstract
PURPOSE:
It is unclear if midlife consumption of dairy and soy food intake, and their components of calcium and isoflavones (in soy), is related to cognitive impairment in elderly.
METHODS:
We used baseline data on lifestyle and habitual diet of 16,948 participants collected during their recruitment into the Singapore Chinese Health Study from 1993 to 1998, and data on their cognitive function, measured using a 30-item Singapore modified Mini-Mental State Examination, during follow-up interviews from 2014 to 2016. We used multivariable logistic regression models to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for developing cognitive impairment.
RESULTS:
Higher dairy intake was associated with a lower risk of cognitive impairment in a dose-dependent manner (P for trend = 0.009). Compared to the lowest quartile of dairy intake, ORs (95% CIs) were 0.93 (0.81-1.07) for the second, 0.88 (0.76-1.01) for the third, and 0.82 (0.72-0.94) for the fourth quartiles of intake. Similar results were found for dairy calcium intake (P for trend = 0.008). However, there was no statistically significant association for intake of soy (OR comparing extreme quartiles 0.99, 95% CI 0.87-1.14, P for trend = 0.92), isoflavones (OR 1.01, 95% CI 0.88-1.15, P for trend = 0.90) or non-dairy calcium (OR 1.06, 95% CI 0.86-1.30, P for trend = 0.81) with risk of cognitive impairment.
CONCLUSIONS:
Dairy intake at midlife could have a protective association against cognitive impairment that may not be attributed to its calcium content alone, while soy or isoflavone intake was not associated with the cognition of elderly in our study.
KEYWORDS:
Calcium; Chinese; Cognitive impairment; Dairy; Isoflavones; Milk; SoyPMID: 31161350

Zinc supplementation improves glycemic control for diabetes prevention and management: a systematic review and meta-analysis of randomized controlled trials.
Wang X, Wu W, Zheng W, Fang X, Chen L, Rink L, Min J, Wang F.
Am J Clin Nutr. 2019 Jun 4. pii: nqz041. doi: 10.1093/ajcn/nqz041. [Epub ahead of print]
PMID: 31161192
Abstract
BACKGROUND:
Although many studies have shown that low zinc status is associated with diabetes, the putative effects of zinc supplementation on glycemic control are inconclusive.
OBJECTIVES:
The aim of this meta-analysis of randomized controlled trials was to assess the effects of zinc supplementation in preventing and managing diabetes.
METHODS:
PubMed, Embase, and the Cochrane Library were searched for articles that were published through February 10, 2019 and contained estimates for the outcomes of interest. The pooled results were then analyzed with the use of a random-effects model.
RESULTS:
Thirty-two placebo-controlled interventions were extracted from 36 publications, involving a total of 1700 participants in 14 countries. Overall, compared with their respective control groups, the subjects in the zinc-supplementation group had a statistically significant reduction in fasting glucose [FG, weighted mean difference (WMD): -14.15 mg/dL; 95% CI: -17.36, -10.93 mg/dL], 2-h postprandial glucose (WMD: -36.85 mg/dL; 95% CI: -62.05, -11.65 mg/dL), fasting insulin (WMD: -1.82 mU/L; 95% CI: -3.10, -0.54 mU/L), homeostasis model assessment for insulin resistance (WMD: -0.73; 95% CI: -1.22, -0.24), glycated hemoglobin (WMD: -0.55%; 95% CI: -0.84, -0.27%), and high-sensitivity C-reactive protein (WMD: -1.31 mg/L; 95% CI: -2.05, -0.56 mg/L) concentrations. Moreover, subgroup analyses revealed that the effects of zinc supplementation on FG are significantly influenced by diabetic status and the formulation of the zinc supplement.
CONCLUSIONS:
Our analysis revealed that several key glycemic indicators are significantly reduced by zinc supplementation, particularly the FG in subjects with diabetes and in subjects who received an inorganic zinc supplement. Together, these findings support the notion that zinc supplementation may have clinical potential as an adjunct therapy for preventing or managing diabetes.
KEYWORDS:
glycemic control; meta-analysis; obesity; prediabetes; type 2 diabetes; zinc supplementation

PMID: 31161192 DOI: 10.1093/ajcn/nqz041

Fast eating is a strong risk factor for new-onset diabetes among the Japanese general population.
Kudo A, Asahi K, Satoh H, Iseki K, Moriyama T, Yamagata K, Tsuruya K, Fujimoto S, Narita I, Konta T, Kondo M, Shibagaki Y, Kasahara M, Watanabe T, Shimabukuro M.
Sci Rep. 2019 Jun 3;9(1):8210. doi: 10.1038/s41598-019-44477-9.
PMID: 31160664
https://www.nature.com/articles/s41598-019-44477-9.pdf
Abstract
Although many studies that have examined the relationship of type and amount of food and the frequency of eating with new onset of diabetes, there are few reports on the relationship between how meals are eaten, such as skipping breakfast, snacking or food ingestion speed, and the onset of diabetes. We investigated the relationship between eating speed, as well as other eating habits such as snacking and skip breakfast, and new onset of diabetes in a nation-wide Japanese cohort. We obtained data from the nation-wide annual health check program in Japan. In 197,825 participants without diabetes in 2008, questionnaires recorded data on the diet habits (eating speed, snack after supper or before sleep, and skipping breakfast) and unadjusted and multivariable-adjusted logistic regression models were used to measure the odds ratio of new-onset diabetes mellitus in a 3-year follow up. The proportion of fast eaters, those who snack after supper, snack before sleep, and skip breakfast was higher in the new-onset diabetes group than in the group who did not develop diabetes mellitus. As compared with the non-fast eater group, fast eaters were generally younger, had higher BMI, had more weight gain from 20 years onwards, and experienced frequent weight fluctuations of ≥3 kg within 1 year. The risk of fast eaters developing diabetes mellitus remained even after correction for multiple factors including age, body weight, rate of weight change, blood pressure, smoking, and alcohol consumption. No other eating habits were independent predictors for onset of diabetes mellitus. Results show that fast eating is a sole predisposing factor among eating habits for new-onset diabetes. Future studies were warranted to evaluate whether avoidance of fast eating is beneficial for prevention of diabetes mellitus.

Therapeutic benefit of combining calorie-restricted ketogenic diet and glutamine targeting in late-stage experimental glioblastoma.
Mukherjee P, Augur ZM, Li M, Hill C, Greenwood B, Domin MA, Kondakci G, Narain NR, Kiebish MA, Bronson RT, Arismendi-Morillo G, Chinopoulos C, Seyfried TN.
Commun Biol. 2019 May 29;2:200. doi: 10.1038/s42003-019-0455-x. eCollection 2019.
PMID: 31149644
https://www.nature.com/articles/s42003-019-0455-x.pdf
Abstract
Glioblastoma (GBM) is an aggressive primary human brain tumour that has resisted effective therapy for decades. Although glucose and glutamine are the major fuels that drive GBM growth and invasion, few studies have targeted these fuels for therapeutic management. The glutamine antagonist, 6-diazo-5-oxo-L-norleucine (DON), was administered together with a calorically restricted ketogenic diet (KD-R) to treat late-stage orthotopic growth in two syngeneic GBM mouse models: VM-M3 and CT-2A. DON targets glutaminolysis, while the KD-R reduces glucose and, simultaneously, elevates neuroprotective and non-fermentable ketone bodies. The diet/drug therapeutic strategy killed tumour cells while reversing disease symptoms, and improving overall mouse survival. The therapeutic strategy also reduces edema, hemorrhage, and inflammation. Moreover, the KD-R diet facilitated DON delivery to the brain and allowed a lower dosage to achieve therapeutic effect. The findings support the importance of glucose and glutamine in driving GBM growth and provide a therapeutic strategy for non-toxic metabolic management.
KEYWORDS:
CNS cancer; Cancer metabolism

Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans.
Jamshed H, Beyl RA, Della Manna DL, Yang ES, Ravussin E, Peterson CM.
Nutrients. 2019 May 30;11(6). pii: E1234. doi: 10.3390/nu11061234.
PMID: 31151228
[pdf availed from PMID site.]
Abstract
Time-restricted feeding (TRF) is a form of intermittent fasting that involves having a longer daily fasting period. Preliminary studies report that TRF improves cardiometabolic health in rodents and humans. Here, we performed the first study to determine how TRF affects gene expression, circulating hormones, and diurnal patterns in cardiometabolic risk factors in humans. Eleven overweight adults participated in a 4-day randomized crossover study where they ate between 8 am and 2 pm (early TRF (eTRF)) and between 8 am and 8 pm (control schedule). Participants underwent continuous glucose monitoring, and blood was drawn to assess cardiometabolic risk factors, hormones, and gene expression in whole blood cells. Relative to the control schedule, eTRF decreased mean 24-hour glucose levels by 4 ± 1 mg/dl (p = 0.0003) and glycemic excursions by 12 ± 3 mg/dl (p = 0.001). In the morning before breakfast, eTRF increased ketones, cholesterol, and the expression of the stress response and aging gene SIRT1 and the autophagy gene LC3A (all p < 0.04), while in the evening, it tended to increase brain-derived neurotropic factor (BNDF; p = 0.10) and also increased the expression of MTOR (p = 0.007), a major nutrient-sensing protein that regulates cell growth. eTRF also altered the diurnal patterns in cortisol and the expression of several circadian clock genes (p < 0.05). eTRF improves 24-hour glucose levels, alters lipid metabolism and circadian clock gene expression, and may also increase autophagy and have anti-aging effects in humans.
KEYWORDS:
circadian rhythms; circadian system; intermittent fasting; meal timing; time-restricted feeding

Association between tea consumption and risk of cancer: a prospective cohort study of 0.5 million Chinese adults.
Li X, Yu C, Guo Y, Bian Z, Shen Z, Yang L, Chen Y, Wei Y, Zhang H, Qiu Z, Chen J, Chen F, Chen Z, Lv J, Li L; China Kadoorie Biobank Collaborative Group.
Eur J Epidemiol. 2019 May 31. doi: 10.1007/s10654-019-00530-5. [Epub ahead of print]
PMID: 31152367
Abstract
Current experimental and epidemiological studies provide inconsistent evidence toward the association between tea consumption and cancer incidence. We investigated whether tea consumption was associated with the incidence of all cancers and six leading types of cancer (lung cancer, stomach cancer, colorectal cancer, liver cancer, female breast cancer and cervix uteri cancer) among 455,981 participants aged 30-79 years in the prospective cohort China Kadoorie Biobank. Tea consumption was assessed at baseline (2004-2008) with an interviewer-administered questionnaire. Cancer cases were identified by linkage to the national health insurance system. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In the present population, daily tea consumers were more likely to be current smokers and daily alcohol consumers. 22,652 incident cancers occurred during 10.1 years follow-up (5.04 cases/1000 person-years). When we restricted analyses to non-smokers and non-excessive alcohol consumers to minimize confounding, tea consumption was not associated with all cancers (daily consumers who added tea leaves > 4.0 g/day vs. less-than-weekly consumers: HR, 1.03; 95%CI, 0.93-1.13), lung cancer (HR, 1.08; CI, 0.84-1.40), colorectal cancer (HR, 1.08; CI, 0.81-1.45) and liver cancer (HR, 1.08; CI, 0.75-1.55), yet might be associated with increased risk of stomach cancer (HR, 1.46; CI, 1.07-1.99). In both less-than-daily and daily tea consumers, all cancer risk increased with the amount of tobacco smoked or alcohol consumed. Our findings suggest tea consumption may not provide preventive effect against cancer incidence.
KEYWORDS:
Breast cancer; Cancer; Cervix uteri cancer; Colorectal cancer; Liver cancer; Lung cancer; Prospective cohort study; Stomach cancer; Tea consumption

Dynamic REM Sleep Modulation by Ambient Temperature and the Critical Role of the Melanin-Concentrating Hormone System.
Komagata N, Latifi B, Rusterholz T, Bassetti CLA, Adamantidis A, Schmidt MH.
Curr Biol. 2019 May 18. pii: S0960-9822(19)30542-1. doi: 10.1016/j.cub.2019.05.009. [Epub ahead of print]
PMID: 31155350
Abstract
Ambient temperature (Ta) warming toward the high end of the thermoneutral zone (TNZ) preferentially increases rapid eye movement (REM) sleep over non-REM (NREM) sleep across species. The control and function of this temperature-induced REM sleep expression have remained unknown. Melanin-concentrating hormone (MCH) neurons play an important role in REM sleep control. We hypothesize that the MCH system may modulate REM sleep as a function of Ta. Here, we show that wild-type (WT) mice dynamically increased REM sleep durations specifically during warm Ta pulsing within the TNZ, compared to both the TNZ cool and baseline constant Ta conditions, without significantly affecting either wake or NREM sleep durations. However, genetically engineered MCH receptor-1 knockout (MCHR1-KO) mice showed no significant changes in REM sleep as a function of Ta, even with increased sleep pressure following a 4-h sleep deprivation. Using MCH-cre mice transduced with channelrhodopsin, we then optogenetically activated MCH neurons time locked with Ta warming, showing an increase in REM sleep expression beyond what Ta warming in yellow fluorescent protein (YFP) control mice achieved. Finally, in mice transduced with archaerhodopsin-T, semi-chronic optogenetic MCH neuronal silencing during Ta warming completely blocked the increase in REM sleep seen in YFP controls. These data demonstrate a previously unknown role for the MCH system in the dynamic output expression of REM sleep during Ta manipulation. These findings are consistent with the energy allocation hypothesis of sleep function, suggesting that endotherms have evolved neural circuits to opportunistically express REM sleep when the need for thermoregulatory defense is minimized.
KEYWORDS:
MCH; NREM sleep; REM sleep; energy allocation hypothesis; lateral hypothalamus; melanin-concentrating hormone; rapid eye movement sleep; resource optimization; sleep function; thermoregulation

Mean nocturnal respiratory rate predicts cardiovascular and all-cause mortality in community-dwelling older men and women.
Baumert M, Linz D, Stone K, McEvoy RD, Cummings S, Redline S, Mehra R, Immanuel S.
Eur Respir J. 2019 May 31. pii: 1802175. doi: 10.1183/13993003.02175-2018. [Epub ahead of print]
PMID: 31151958
Abstract
Respiratory rate (RR) predicts in-hospital and short-term mortality in patients with a variety of pathophysiological conditions, but its predictive value for long-term cardiovascular (CV) and all-cause mortality in the general population is unknown. Here, we investigated the relationship between mean nocturnal RR and mortality in community-dwelling older men and women.We measured mean nocturnal RR during sleep from overnight polysomnography in 2686 men participating in the Osteoporotic Fractures in Men Study (MrOS) sleep study and 406 women participating in the Study of Osteoporotic Fractures (SOF) to investigate the relationship between mean nocturnal RR with long-term CV and all-cause mortality.One hundred sixty-six men (6.1%) in the MrOS cohort (8.9±2.6 years follow-up) and 46 women (11.2%) in the SOF cohort (6.4±1.6 years follow-up) died from CV disease. All-cause mortality was 51.2% and 26.1% during 13.7±3.7 and 6.4±1.6 years follow-up in the MrOS Sleep and the SOF cohort, respectively. Multivariable Cox regression analysis adjusted for significant covariates demonstrated that RR dichotomised at 16 breaths per minute was independently associated with CV mortality (MrOS: HR=1.57 [1.14-2.15], p=0.005; SOF: HR=2.58 [1.41-4.76]), p=0.002) and all-cause mortality (MrOS: HR=1.18 [1.04-1.32], p=0.007; SOF: HR=1.50 [1.02-2.20], p=0.04).In community-dwelling older men and women, polysomnography-derived mean nocturnal RR≥16 breaths per minute is an independent predictor of long-term CV and all-cause mortality. Whether nocturnal mean RR can be used as a risk marker warrants further prospective studies.

Physical activity and risk of instant and 28-day case-fatality in myocardial infarction.
Peytz NC, Jabbari R, Bojesen SE, Nordestgaard B, Schnohr P, Prescott E.
PLoS One. 2019 May 31;14(5):e0217398. doi: 10.1371/journal.pone.0217398. eCollection 2019.
PMID: 31150433
https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0217398&type=printable
Abstract
BACKGROUND:
While physical activity reduces risk of developing myocardial infarction (MI), it is unknown whether a history of physical activity is also protective of fatal arrhythmia and case-fatality in patients who have suffered an acute MI.
METHODS:
104,801 individuals included in 2003-2014 in the Copenhagen General Population Study (CGPS), a prospective population-based study with self-reported leisure time physical activity (LTPA) in three categories measured at baseline, were followed until 2014 through national registries. The 1,517 individuals who suffered a first time MI during follow-up constituted the study population. Outcomes were fatal MI, defined as date of death same as date of MI (including out-of-hospital deaths) and 28-day fatality. Through multivariable analyses the association between baseline LTPA and outcomes were assessed adjusted for CVD risk factors.
RESULTS:
Of 1,517 MI events, 117 (7.7%) were fatal and another 79 (5.6%) lead to death within 28 days. Median time from baseline to MI was 3.6 years (IQR 1.7-5.8). LTPA was associated with lower risk of fatal MI with odds ratios of 0.40 (95% CI: 0.22-0.73) for light and 0.41 (0.22-0.76) for moderate/high LTPA after multivariable adjustment with sedentary LTPA as reference. Age, alcohol-intake, education and smoking were identified as other predictors for fatal MI. We found no association between LTPA and 28-day case fatality.
CONCLUSIONS:
Among individuals with MI, those that have engaged in any light or moderate physical activity were more likely to survive their MI. Results are consistent with effect of exercise preconditioning on risk of fatal arrhythmia.

[AlPater]

Methionine restriction delays senescence and suppresses the senescence-associated secretory phenotype in the kidney through endogenous hydrogen sulfide.
Wang SY, Wang WJ, Liu JQ, Song YH, Li P, Sun XF, Cai GY, Chen XM.
Cell Cycle. 2019 Jun 5:1-15. doi: 10.1080/15384101.2019.1618124. [Epub ahead of print]
PMID: 31164038
https://sci-hub.tw/10.1080/15384101.2019.1618124
Abstract
Aging is a risk factor for various acute and chronic kidney injuries. Kidney aging is accompanied by the secretion of growth factors, proteases, and inflammatory cytokines, known as the senescence-associated secretory phenotype (SASP). These factors accelerate the aging process and senescence-associated changes. Delaying kidney senescence may prevent acute and chronic kidney injury. Methionine restriction (MR) was found to be an effective intervention for delaying senescence. However, the mechanism of MR remains unclear. In this study, we investigated the effect of MR on the survival rate and renal aging of C57BL/6 mice and examined the relevant mechanisms. MR increased the survival rate and decreased the levels of senescence markers in the aging kidney. Both in vivo and in vitro, MR upregulated the transsulfuration pathway to increase H2S production, downregulated senescence markers and the SASP, and activated AMPK. The ability of MR to delay aging was reduced when AMPK was inhibited. These results suggest that MR may slow animal aging and kidney senescence through H2S production and AMPK pathway activation. 
Abbreviations: DR: diet restriction; MR: methionine restriction; SASP: senescence-associated secretory phenotype; AL: ad libitum; CKD, chronic kidney disease; AKI: acute kidney disease; TSP: transsulfuration pathway; CGL: cystathionine g-lyase; H2S: hydrogen sulfide; AMPK: AMP-activated protein kinase; mTOR: mammalian target of rapamycin; IS: indoxyl sulfate; CC: compound C.
KEYWORDS:
Senescence; hydrogen sulfide; methionine restriction; renal; senescence-associated secretory phenotype

Lipid Profile and Risk of Bone Fracture: A Systematic Review and Meta-Analysis of Observational Studies.
Ghorabi S, Shab-Bidar S, Sadeghi O, Nasiri M, Khatibi SR, Djafarian K.
Endocr Res. 2019 Jun 5:1-17. doi: 10.1080/07435800.2019.1625057. [Epub ahead of print]
PMID: 31165667
Abstract
Purpose: Earlier studies have linked lipid profile to osteoporotic fractures; however, to our knowledge, no study had summarized available data on this relationship. We aimed to summarize the current evidence on the association between lipid profile and bone fractures. Material and Methods: A systematic search of PubMed and Scopus was done to find relevant published studies until March 2018. To combine effect sizes, we applied fixed- or random-effects analysis, where appropriate. Cochran's Q test and I2 were used to assess between-study heterogeneity. Results: Overall, 11 studies (seven prospective, three cross-sectional and one case-control studies) were included in the current systematic review. Out of them, 10 studies with a total sample size of 60,484 individuals, aged 25 years or more, were used in the meta-analysis. The results showed that total cholesterol concentration was positively associated with risk of bone fracture; such that a 50-mg/dl increase in plasma level of TC was associated with 15% greater odds of bone fracture (combined effect size: 1.15, 95% CI: 1.02-1.30, P = .02). Furthermore, we found that individuals with a decreased level of HDL (<40 mg/dl) had a lower risk of bone fracture compared with those with a normal level (≥40 mg/dl) (combined effect size: 0.82, 95% CI: 0.71-0.96, P = .01). No significant association was found between plasma level of TG and LDL with the risk of bone fractures either in prospective or cross-sectional studies. Conclusions: We found that plasma levels of total cholesterol were positively associated with bone fractures. In addition, decreased levels of HDL were associated with an increased risk of osteoporotic fractures. Abbreviations: TG: triglycerides, TC: total cholesterol, HDL: high-density lipoprotein, LDL: low-density lipoprotein, OR: odds ratio, RR: relative risk, HR: hazard ratio, DXA: dual-energy X-ray absorptiometry, ICD: International Classification of Diseases, SD: standard deviation.
KEYWORDS:
Cholesterol; bone fracture; high-density lipoprotein; lipoproteins; meta-analysis

Duration and Quality of Sleep and Risk of Physical Function Impairment and Disability in Older Adults: Results from the ENRICA and ELSA Cohorts.
Campanini MZ, Mesas AE, Carnicero-Carreño JA, Rodríguez-Artalejo F, Lopez-Garcia E.
Aging Dis. 2019 Jun 1;10(3):557-569. doi: 10.14336/AD.2018.0611. eCollection 2019 Jun.
PMID: 31165000
[pdf availed from Pubmed site.]
Abstract
Sleep duration and quality have been associated with poor physical function, but both the temporality of the association and the independence of sleep duration and quality are unclear. We examined the prospective association of sleep duration and quality with physical function impairment and disability in older adults. Data were taken from participants in the Seniors-ENRICA (2012-2015, n= 1,773) and in the ELSA cohort (waves 4 and 6, n=4,885) aged ≥60 years. Sleep duration and quality were self-reported. Physical function impairment and disability was obtained either from self-reports (ENRICA and ELSA) or from performance assessment (ENRICA). Logistic regression models were adjusted for potential confounders. After a follow-up of 2.0-2.8 years, no association was found between changes in sleep duration and physical function impairment or disability. However, in both studies, poor general sleep quality was linked to higher risk of impaired agility [OR: 1.93 (95% CI: 1.30-2.86) in Seniors-ENRICA and 1.65 (1.24-2.18) in ELSA study] and mobility [1.46 (0.98-2.17) in Seniors-ENRICA and 1.59 (1.18-2.15) in ELSA study]. Poor general sleep quality was also associated with decreased physical component summary (PCS) [1.39 (1.05-1.83)], disability in instrumental activities of daily living [1.59 (0.97-2.59)] and in basic activities of daily living [1.73 (1.14-2.64)] in Seniors-ENRICA. In addition, compared to those with no sleep complaints, participants with 2 or more sleep complaints had greater risk of impaired agility, impaired mobility, decreased PCS and impaired lower extremity function in both cohorts. Poor sleep quality was associated with higher risk of physical impairment and disability in older adults from Spain and from England.
KEYWORDS:
physical activity.; physical function; sleep

[AlPater]

Egg Consumption and Risk of Total and Cause-Specific Mortality: An Individual-Based Cohort Study and Pooling Prospective Studies on Behalf of the Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group.
Mazidi M, Katsiki N, Mikhailidis DP, Pencina MJ, Banach M.
J Am Coll Nutr. 2019 Jun 7:1-12. doi: 10.1080/07315724.2018.1534620. [Epub ahead of print]
PMID: 31173548
https://sci-hub.tw/10.1080/07315724.2018.1534620
Abstract
The associations of egg consumption with total, coronary heart disease (CHD), and stroke mortality are poorly understood. We prospectively evaluated the link between total, CHD, and stroke mortality with egg consumption using a randomly selected sample of U.S. adults. Next we validated these results within a meta-analysis and systematic review of all available prospective results. We assessed the mean of cardiometabolic risk factors across the intake of eggs. We made the analysis based on data from the National Health and Nutrition Examination Surveys (NHANES; 1999-2010). In NHANES, vital status through December 31, 2011, was ascertained. Cox proportional hazard regression models were used to relate baseline egg consumption with all-cause and cause-specific mortality. PubMed, Scopus, Web of Science, and Google Scholar databases were also searched (up to December 2017). The DerSimonian-Laird method and generic inverse variance methods were used for quantitative data synthesis. Overall, 23,524 participants from NHANES were included (mean age of 47.7 years; 48.7% were men). Across increasing the intake of eggs, adjusted mean levels of cardiometabolic risk factors worsened. Adjusted logistic regression showed that participants in the highest category of egg intake had a greater risk of diabetes (T2DM; 30%) and hypertension (HTN; 48%). With regard to total and CHD mortality, multivariable Cox regression in a fully adjusted model showed no link in males and females. In males, egg intake had a reverse (66%) association with stroke mortality, while this link was not significant among females. The results of pooling data from published prospective studies also showed no link between CHD and total mortality with egg consumption, whereas we observed a reverse (28%) association between egg intake and stroke mortality. These findings were robust after sensitivity analysis. According to our findings, egg intake had no association with CHD and total mortality, whereas was associated with lower risk of mortality from stroke. Egg consumption was associated with T2DM, HTN, C-reactive protein, and markers of glucose/insulin homeostasis. If confirmed in clinical trials (causation), this information may have applications for population-wide health measures. Key teaching points No link between total and CHD mortality with eggs intake in males and females. In males, egg intake had a reverse association with stroke mortality, while this link was not significant among females. The results of pooling data from published prospective studies also showed no link between CHD and total mortality with egg consumption, whereas we observed a reverse association between egg intake and stroke mortality.
KEYWORDS:
Egg; coronary heart disease; diabetes; hypertension; mortality; stroke

Habitual Alcohol Intake Modifies Relationship of Uric Acid to Incident Chronic Kidney Disease.
Okada Y, Uehara S, Shibata M, Koh H, Oue K, Kambe H, Morimoto M, Sato KK, Hayashi T.
Am J Nephrol. 2019 Jun 6:1-8. doi: 10.1159/000500707. [Epub ahead of print]
PMID: 31170706
Abstract
BACKGROUND:
Previous studies showed that higher serum uric acid levels increased the risk of chronic kidney disease (CKD), but moderate alcohol consumption decreased it. The comparative importance of serum uric acid levels and habitual alcohol consumption as risk factors for CKD remain undefined. We therefore evaluated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD.
METHODS:
A prospective cohort study of 9,116 middle-aged nondiabetic -Japanese men without CKD nor proteinuria who were not taking antihypertensive medications nor urate-lowering medications at entry. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. We investigated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD during an 11-year observation period. Daily alcohol consumption was classified into 4 groups: nondrinkers, light drinkers (0.1-23.0 g ethanol/day), moderate drinkers (23.1-46.0 g ethanol/day), and heavy drinkers (≥46.1 g ethanol/day). Cox proportional hazards models were used in multivariate analysis.
RESULTS:
During the 79,361 person-years follow-up period, a total of 1,230 subjects developed CKD. In multivariate models, higher serum uric acid levels increased risk of CKD; and moderate daily alcohol consumption decreased the risk. Multiple-adjusted hazard ratios of CKD were 1.38 (95% CI 1.11-1.70), 1.58 (95% CI 1.28-1.95), 2.27 (95% CI 1.86-2.77), and 3.12 (95% CI 2.56-3.81) for quintile 2, quintile 3, quintile 4, and quintile 5 of serum uric acid levels, respectively, compared with quintile 1, and that for moderate drinkers was 0.55 (95% CI 0.46-0.66) compared with nondrinkers. In the joint analysis of alcohol consumption and serum uric acid, moderate drinkers with the lowest tertile of serum uric acid levels had the lowest risk of CKD, but nondrinkers with the highest tertile of serum uric acid levels had the highest risk of CKD.
CONCLUSIONS:
Serum uric acid level and daily alcohol consumption were independently associated with the risk of CKD. Nondrinkers with the highest serum uric acid level had the highest risk of CKD.
KEYWORDS:
Alcohol; Chronic kidney disease; Estimated glomerular filtration rate; Prospective cohort study; Uric acid

Prospective investigation of serum metabolites, coffee drinking, liver cancer incidence, and liver disease mortality.
Loftfield E, Rothwell JA, Sinha R, Keski-Rahkonen P, Robinot N, Albanes D, Weinstein SJ, Derkach A, Sampson J, Scalbert A, Freedman ND.
J Natl Cancer Inst. 2019 Jun 5. pii: djz122. doi: 10.1093/jnci/djz122. [Epub ahead of print]
PMID: 31168595
Abstract
BACKGROUND:
Coffee has been consistently associated with lower risk of liver cancer and chronic liver disease, suggesting that coffee affects mechanisms underlying disease development.
METHODS:
We measured serum metabolites using untargeted metabolomics in 1:1 matched nested case-control studies of liver cancer (n = 221 cases) and fatal liver disease (n = 242 cases) in the ATBC cohort (N = 29,133). Associations between baseline coffee drinking and metabolites were identified using linear regression; conditional logistic regression models were used to identify associations with subsequent outcomes.
RESULTS:
Overall, 21 metabolites were associated with coffee drinking and also each subsequent endpoint; nine metabolites and trigonelline, a known coffee biomarker, were identified. Tyrosine and two bile acids, glycochenodeoxycholic acid (GCDCA) and glycocholic acid (GCA), were inversely associated with coffee but positively associated with both outcomes; odds ratios (ORs) comparing the 90th to 10th percentile (modeled on a continuous basis) ranged from 3.93 (95% CI = 2.00-7.74) for tyrosine to 4.95 (95% CI = 2.64-9.29) for GCA and from 4.00 (95% CI = 2.42-6.62) for GCA to 6.77 (95% CI = 3.62-12.65) for GCDCA for liver cancer and fatal liver disease, respectively. The remaining six metabolites and trigonelline were positively associated with coffee drinking but inversely associated with both outcomes; ORs ranged from 0.16 to 0.37. Associations persisted following diet-adjustment and for outcomes occurring >10 years after blood collection.
CONCLUSIONS:
A broad range of compounds were associated with coffee drinking, incident liver cancer and liver disease death over 27 years of follow-up. These associations provide novel insight into chronic liver disease and liver cancer etiology and support a possible hepatoprotective effect of coffee.
KEYWORDS:
bile acids; cirrhosis; coffee; hepatocellular carcinoma; metabolomics

Towards a unified mechanistic theory of aging.
Barja G.
Exp Gerontol. 2019 Jun 4. pii: S0531-5565(19)30173-1. doi: 10.1016/j.exger.2019.05.016. [Epub ahead of print] Review.
PMID: 31173843
Abstract
A large amount of the longevity-modulating genes discovered during the last two decades are highly conserved during evolution from yeast and invertebrates to mammals. Many different kinds of evidence converge in the concept that life extending manipulations like the dietary restrictions or rapamycin signal the nucleus specifically changing gene expression to increase longevity. The response of the cell aging regulation system is to change the level of activity of many different aging effectors to modulate longevity. Aging effectors include mitROS production, lipid unsaturation, autophagy, mitochondrial DNA repair and possibly others like apoptosis, proteostasis, or telomere shortening, corresponding to different classic theories of aging. The constitutive spontaneous activity of this aging regulating system, likely including epigenetics, can also explain species longevity. The aging regulating system reconciles the previously considered independent theories of aging bringing them together into a single unified theory of aging.
KEYWORDS:
Aging; Autophagy; Free radicals; Longevity; Reactive oxygen species production

Carbohydrate-Rich Diet Is Associated with Increased Risk of Incident Chronic Kidney Disease in Non-Diabetic Subjects.
Nam KH, An SY, Joo YS, Lee S, Yun HR, Jhee JH, Han SH, Yoo TH, Kang SW, Park JT.
J Clin Med. 2019 Jun 4;8(6). pii: E793. doi: 10.3390/jcm8060793.
PMID: 31167515
Abstract
Despite the potential relationship with metabolic derangements, the association between dietary carbohydrate intake and renal function remains unknown. The present study investigated the impact of dietary carbohydrate intake on the development of incident chronic kidney disease (CKD) in a large-scale prospective cohort with normal renal function. A total of 6746 and 1058 subjects without and with diabetes mellitus (DM) were analyzed, respectively. Carbohydrate intake was assessed by a 24-h dietary recall food frequency questionnaire. The primary endpoint was CKD development, defined as a composite of estimated glomerular filtration rate (eGFR) of ≤60 mL/min/1.73 m2 and the development of proteinuria. CKD newly developed in 20.1% and 36.0% of subjects during median follow-ups of 140 and 119 months in the non-DM and DM subjects, respectively. Categorization of non-DM subjects into dietary carbohydrate density quartiles revealed a significantly higher risk of CKD development in the third and fourth quartiles than in the first quartile (P = 0.037 for first vs. third; P = 0.001 for first vs. fourth). A significant risk elevation was also found with increased carbohydrate density when carbohydrate density was treated as a continuous variable (P = 0.008). However, there was no significant difference in the incident CKD risk among those with DM according to dietary carbohydrate density quartiles. Carbohydrate-rich diets may increase the risk of CKD development in non-DM subjects.
KEYWORDS:
carbohydrate density; chronic kidney disease; dietary carbohydrate; renal nutrition

Prospective Association of Serum and Dietary Magnesium with Colorectal Cancer Incidence.
Polter E, Onyeaghala GC, Lutsey PL, Folsom AR, Joshu CE, Platz EA, Prizment AE.
Cancer Epidemiol Biomarkers Prev. 2019 Jun 5. pii: cebp.1300.2018. doi: 10.1158/1055-9965.EPI-18-1300. [Epub ahead of print]
PMID: 31167754
Abstract
BACKGROUND:
Laboratory and epidemiological research suggests a protective role of magnesium in colorectal cancer development. We estimated the associations of serum and dietary magnesium with colorectal cancer incidence in the Atherosclerosis Risk in Communities (ARIC) study.
METHODS:
Serum magnesium concentration was measured in blood collected twice (1987-1989 and 1990-1992) and averaged. Dietary magnesium was assessed by food-frequency questionnaire administered twice (1987-1989 and 1993-1995) and averaged. For both dietary and serum magnesium, the averaged measures were categorized into quintiles for analysis. Analyses included 315 colorectal cancer cases among 13,009 participants for serum magnesium (followed for a median of 20.4 years), and 256 cases among 10,971 participants for dietary magnesium (followed for a median of 17.5 years). Cox proportional hazards regression was used to calculate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI).
RESULTS:
Multivariable-adjusted HRs (95% CI) of colorectal cancer for the highest four quintiles compared to the first quintile of serum magnesium were: Q2: 0.70 (0.49-0.99); Q3: 0.68 (0.47-1.00) Q4: 0.87 (0.62-1.21); and Q5: 0.79 (0.57-1.11; p-trend=0.04). An inverse association was present in females (HR for Q5 vs Q1: 0.59, 95% CI: 0.36-0.98, p-trend=0.01), but not males (HR for Q5 vs Q1: 1.10, 95% CI: 0.67-1.79, p-trend=0.92; p-interaction=0.34). Dietary magnesium was not statistically significantly associated with colorectal cancer risk.
CONCLUSIONS:
Our study found a higher risk of colorectal cancer with lower serum magnesium among females, but not males.
IMPACT:
If our findings are confirmed, maintaining adequate serum magnesium levels may be important for colorectal cancer prevention.

Effects of aspirin and non-steroidal anti-inflammatory drugs on the risk of cholangiocarcinoma: a meta-analysis.
Lapumnuaypol K, Tiu A, Thongprayoon C, Wijarnpreecha K, Ungprasert P, Mao MA, Cheungpasitporn W.
QJM. 2019 Jun 1;112(6):421-427. doi: 10.1093/qjmed/hcz039.
PMID: 30753687
Abstract
BACKGROUND:
Non-steroidal anti-inflammatory drugs (NSAIDs) can suppress the proliferation of cholangiocarcinoma (CCA) cells in vitro through inhibition of cyclooxygenase-2. However, the effects of aspirin and NSAIDs on the risk of CCA remain unclear. We performed this meta-analysis to assess the risk of biliary tract cancers in patients who take aspirin and/or NSAIDs.
METHODS:
A systematic review was conducted utilizing MEDLINE, EMBASE, Cochrane databases from inception through October 2017 to identify studies that assessed the association of aspirin and/or NSAIDs use with risk of biliary tract cancers including CCA, gallbladder cancer and ampulla of Vater cancer. Effect estimates from the studies were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird.
RESULTS:
Five observational studies with a total of 9 200 653 patients were enrolled. The pooled OR of CCA in patients with aspirin use was 0.56 (95% CI, 0.32-0.96). Egger's regression asymmetry test was performed and showed no publication bias for the association between aspirin use and CCA with P = 0.42. There was no significant association between NSAIDs use and CCA, with a pooled OR of 0.79 (95% CI, 0.28-2.21). One study showed a significant association between aspirin use and reduced risk of gallbladder cancer with OR of 0.37 (0.17-0.80). However, there was no significant association between aspirin and ampulla of Vater cancer with OR of 0.22 (0.03-1.65).
CONCLUSIONS:
Our study demonstrates a significant association between aspirin use and a 0.56-fold decreased risk of CCA. However, there is no association between the use of NSAIDs and CCA.

[AlPater]

Intakes of long-chain omega-3 polyunsaturated fatty acids and non-fried fish in relation to incidence of chronic kidney disease in young adults: a 25-year follow-up.
Park I, Xun P, Tsinovoi CL, Klemmer P, Liu K, He K.
Eur J Nutr. 2019 Jun 7. doi: 10.1007/s00394-019-02022-4. [Epub ahead of print]
PMID: 31175412
https://sci-hub.tw/10.1007/s00394-019-02022-4
Abstract
PURPOSE:
The prevalence of chronic kidney disease (CKD) is increasing rapidly in many countries and has become a major public health concern. Although intakes of long-chain omega-3 polyunsaturated fatty acids (LCω3PUFA) and its food source-fish-may have renal protective effects, little is known about the longitudinal association between these dietary factors and CKD incidence.
METHODS:
A total of 4133 healthy individuals of black and white race aged 18-30 at baseline (1985-1986) from the Coronary Artery Risk Development in Young Adults study were enrolled and followed up over 25 years. LCω3PUFA and fish intake were assessed by an interview-based dietary history questionnaire at baseline, year 7 (1992-1993) and 20 (2005-2006).
RESULTS:
Four hundred and eighty-nine incident cases of CKD were identified. After adjustment for potential confounders, LCω3PUFA intake was inversely associated with CKD incidence [HR = 0.73 (95% CI 0.60-0.89), P = 0.002, with one standard division (0.19 g/day) increment in LCω3PUFA]. This inverse association was persisted among females [0.64 (95% CI 0.48, 0.84; P = 0.002], but not males (Pinteraction = 0.070). A marginal significant inverse association was also found between non-fried fish consumption and CKD incidence (HR = 0.86, 95% CI 0.73, 1.01; P = 0.073).
CONCLUSIONS:
Dietary LCω3PUFA intake was inversely associated with incidence of CKD among American young adults over 25 years of follow-up. The suggestive evidence of the inverse association between non-fried fish consumption with CKD incidence needs further confirmation.
KEYWORDS:
Chronic kidney disease; Fish; Long-chain omega-3 polyunsaturated fatty acids; Proteinuria

A Meta-Analysis of 46 Studies Identified by the FDA Demonstrates that Soy Protein Decreases Circulating LDL and Total Cholesterol Concentrations in Adults.
Blanco Mejia S, Messina M, Li SS, Viguiliouk E, Chiavaroli L, Khan TA, Srichaikul K, Mirrahimi A, Sievenpiper JL, Kris-Etherton P, Jenkins DJA.
J Nutr. 2019 Jun 1;149(6):968-981. doi: 10.1093/jn/nxz020.
PMID: 31006811
Abstract
BACKGROUND:
Certain plant foods (nuts and soy protein) and food components (viscous fibers and plant sterols) have been permitted by the FDA to carry a heart health claim based on their cholesterol-lowering ability. The FDA is currently considering revoking the heart health claim for soy protein due to a perceived lack of consistent LDL cholesterol reduction in randomized controlled trials.
OBJECTIVE:
We performed a meta-analysis of the 46 controlled trials on which the FDA will base its decision to revoke the heart health claim for soy protein.
METHODS:
We included the 46 trials on adult men and women, with baseline circulating LDL cholesterol concentrations ranging from 110 to 201 mg/dL, as identified by the FDA, that studied the effects of soy protein on LDL cholesterol and total cholesterol (TC) compared with non-soy protein. Two independent reviewers extracted relevant data. Data were pooled by the generic inverse variance method with a random effects model and expressed as mean differences with 95% CI. Heterogeneity was assessed and quantified.
RESULTS:
Of the 46 trials identified by the FDA, 43 provided data for meta-analyses. Of these, 41 provided data for LDL cholesterol, and all 43 provided data for TC. Soy protein at a median dose of 25 g/d during a median follow-up of 6 wk decreased LDL cholesterol by 4.76 mg/dL (95% CI: -6.71, -2.80 mg/dL, P < 0.0001; I2 = 55%, P < 0.0001) and decreased TC by 6.41 mg/dL (95% CI: -9.30, -3.52 mg/dL, P < 0.0001; I2 = 74%, P < 0.0001) compared with non-soy protein controls. There was no dose-response effect or evidence of publication bias for either outcome. Inspection of the individual trial estimates indicated most trials (∼75%) showed a reduction in LDL cholesterol (range: -0.77 to -58.60 mg/dL), although only a minority of these were individually statistically significant.
CONCLUSIONS:
Soy protein significantly reduced LDL cholesterol by approximately 3-4% in adults. Our data support the advice given to the general public internationally to increase plant protein intake.
KEYWORDS:
LDL cholesterol; cardiovascular disease prevention; lipids; meta-analysis; soy protein; total cholesterol

[AlPater]

Impact of dietary protein intake and obesity on lean mass in middle-aged individuals after a 12-year follow-up: The Korean Genome and Epidemiology Study (KoGES).
So E, Choi SK, Joung H.
Br J Nutr. 2019 Jun 10:1-21. doi: 10.1017/S000711451900117X. [Epub ahead of print]
PMID: 31177993
Abstract
This study investigated the association between protein intake and lean mass according to obesity status over a 12-year period. Data on 4,412 participants aged 40-69 years were obtained from the Korean Genome and Epidemiology Study. The usual dietary protein intake of these participants was assessed at baseline using a semi-quantitative food frequency questionnaire. Body composition was measured using a bioelectrical impedance analysis at baseline and after a 12-year follow-up. Linear mixed effects models were used to examine the associations between lean mass after a 12-year follow-up and protein intake at baseline. After adjusting for covariates and lean mass at baseline, comparisons between the highest and lowest tertiles revealed that dietary protein intake was positively associated with lean mass in both men (β=0.79, p=0.001) and women (β=0.28, p=0.082) after the 12-year period; however, those differences were attenuated after additional adjustment for fat mass at baseline and were stronger in the normal-weight group (men, β=0.85, p=0.002; women, β=0.97, p&lt;0.001) but were not detected in the obese group. In the obese group, age (men, β=4.08, p&lt;0.001; women, β=2.61, p&lt;0.001) and regular physical activity (men, β=0.88, p=0.054; women, β=0.76, p&lt;0.001) were significantly associated with lean mass after 12 years of follow-up. The results of this study showed that protein intake may contribute to the prevention of ageing-related lean mass loss; however, the impact of this intake may vary depending on obesity status. Therefore, the maintenance of a healthy body weight during ageing through enhanced protein intake is likely to confer health benefits.
KEYWORDS:
Korean Genome and Epidemiology Study (KoGES); cohort study; lean mass; obesity; protein intake

Time-Restricted Eating to Prevent and Manage Chronic Metabolic Diseases.
Chaix A, Manoogian ENC, Melkani GC, Panda S.
Annu Rev Nutr. 2019 Jun 10. doi: 10.1146/annurev-nutr-082018-124320. [Epub ahead of print]
PMID: 31180809
https://sci-hub.tw/10.1146/annurev-nutr-082018-124320
Abstract
Molecular clocks are present in almost every cell to anticipate daily recurring and predictable changes, such as rhythmic nutrient availability, and to adapt cellular functions accordingly. At the same time, nutrient-sensing pathways can respond to acute nutrient imbalance and modulate and orient metabolism so cells can adapt optimally to a declining or increasing availability of nutrients. Organismal circadian rhythms are coordinated by behavioral rhythms such as activity-rest and feeding-fasting cycles to temporally orchestrate a sequence of physiological processes to optimize metabolism. Basic research in circadian rhythms has largely focused on the functioning of the self-sustaining molecular circadian oscillator, while research in nutrition science has yielded insights into physiological responses to caloric deprivation or to specific macronutrients. Integration of these two fields into actionable new concepts in the timing of food intake has led to the emerging practice of time-restricted eating. In this paradigm, daily caloric intake is restricted to a consistent window of 8-12 h. This paradigm has pervasive benefits on multiple organ systems. 

Methionine is a metabolic dependency of tumor-initiating cells.
Wang Z, Yip LY, Lee JHJ, Wu Z, Chew HY, Chong PKW, Teo CC, Ang HY, Peh KLE, Yuan J, Ma S, Choo LSK, Basri N, Jiang X, Yu Q, Hillmer AM, Lim WT, Lim TKH, Takano A, Tan EH, Tan DSW, Ho YS, Lim B, Tam WL.
Nat Med. 2019 May;25(5):825-837. doi: 10.1038/s41591-019-0423-5. Epub 2019 May 6. Erratum in: Nat Med. 2019 May 21;:.
PMID: 31061538
https://sci-hub.tw/10.1038/s41591-019-0423-5
Abstract
Understanding cellular metabolism holds immense potential for developing new classes of therapeutics that target metabolic pathways in cancer. Metabolic pathways are altered in bulk neoplastic cells in comparison to normal tissues. However, carcinoma cells within tumors are heterogeneous, and tumor-initiating cells (TICs) are important therapeutic targets that have remained metabolically uncharacterized. To understand their metabolic alterations, we performed metabolomics and metabolite tracing analyses, which revealed that TICs have highly elevated methionine cycle activity and transmethylation rates that are driven by MAT2A. High methionine cycle activity causes methionine consumption to far outstrip its regeneration, leading to addiction to exogenous methionine. Pharmacological inhibition of the methionine cycle, even transiently, is sufficient to cripple the tumor-initiating capability of these cells. Methionine cycle flux specifically influences the epigenetic state of cancer cells and drives tumor initiation. Methionine cycle enzymes are also enriched in other tumor types, and MAT2A expression impinges upon the sensitivity of certain cancer cells to therapeutic inhibition.

[AlPater]

Associations Between Linoleic Acid Intake and Incident Type 2 Diabetes Among U.S. Men and Women.
Zong G, Liu G, Willett WC, Wanders AJ, Alssema M, Zock PL, Hu FB, Sun Q.
Diabetes Care. 2019 Jun 10. pii: dc190412. doi: 10.2337/dc19-0412. [Epub ahead of print]
PMID: 31182488
Abstract
OBJECTIVE:
To investigate the association between intakes of n-6 polyunsaturated fatty acids (PUFAs) and type 2 diabetes risk in three prospective cohort studies of U.S. men and women.
RESEARCH DESIGN AND METHODS:
We followed 83,648 women from the Nurses' Health Study (NHS; 1980-2012), 88,610 women from NHSII (1991-2013, and 41,771 men from the Health Professionals Follow-Up Study (1986-2012). Dietary data was collected every 2-4 years by using validated food-frequency questionnaires. Self-reported incident diabetes, identified biennially, was confirmed by using a validated supplementary questionnaire.
RESULTS:
During 4.93 million person-years of follow-up, 18,442 type 2 diabetes cases were documented. Dietary n-6 PUFAs accounted for 4.4-6.8% of total energy, on average, and consisted primarily of linoleic acid (LA; ≥98%). In multivariate-adjusted models, hazard ratios (95% CIs) of type 2 diabetes risk comparing extreme n-6 PUFA quintiles (highest vs. lowest) were 0.91 (0.85, 0.96; P trend = 0.002) for total n-6 PUFAs and 0.92 (0.87, 0.98; P trend = 0.01) for LA. In an isocaloric substitution model, diabetes risk was 14% (95% CI 5%, 21%; P = 0.002) lower when LA isocalorically replaced saturated fats (5% of energy), 17% (95% CI 9%, 24%; P < 0.001) lower for trans fats (2% energy), or 9% (95% CI 17%, 0.1%; P = 0.047) lower for carbohydrates (5% energy). Replacing n-3 PUFAs or monounsaturated fats with LA was not significantly associated with type 2 diabetes risk.
CONCLUSIONS:
Our study provides additional evidence that LA intake is inversely associated with risk of type 2 diabetes, especially when replacing saturated fatty acids, trans fats, or carbohydrates.

Dietary Glycemic Index and Glycemic Load and the Risk of Prostate Cancer: An Updated Systematic Review and Dose-Response Meta-Analysis.
Sadeghi A, Sadeghi O, Khodadost M, Pirouzi A, Hosseini B, Saedisomeolia A.
Nutr Cancer. 2019 Jun 11:1-10. doi: 10.1080/01635581.2019.1621356. [Epub ahead of print]
PMID: 31184513
https://sci-hub.tw/10.1080/01635581.2019.1621356
Abstract
A meta-analysis in 2015 revealed no significant association between glycemic index (GI), glycemic load (GL), and prostate cancer. Moreover, until now, no study has examined the dose-response association of GI, GL, and prostate cancer yet. The online databases were searched by two independent researchers for relevant publications up to Jan. 2019, using relevant keywords. Nine studies including five prospective and four case-control studies were included in the current systematic review and meta-analysis. These studies have included 290,911 individuals. We found a significant positive dose-response association between dietary GI and prostate cancer (Pnonlinearity = 0.03). Comparing individuals in the highest category of GI with those in the lowest category, no significant association was found between GI and prostate cancer (combined effect size: 1.08, 95% CI: 0.97-1.19, P = 0.17). Furthermore, no significant association was seen between dietary GL and prostate cancer in both dose-response analysis and when comparing the highest versus lowest categories of GL (combined effect size: 1.03, 95% CI: 0.91-1.16, P = 0.65). In conclusion, we found a significant positive dose-response association between dietary GI and prostate cancer. However, significant association was not seen for dietary GL.

Metformin prevents murine ovarian aging.
Qin X, Du D, Chen Q, Wu M, Wu T, Wen J, Jin Y, Zhang J, Wang S.
Aging (Albany NY). 2019 Jun 10. doi: 10.18632/aging.102016. [Epub ahead of print]
PMID: 31182682
Abstract
A number of studies have shown that metformin can delay aging process and extend healthy lifespan in animals. However, its role in female reproductive lifespan is unclear. This study was aimed to explore the potential anti-aging effect of metformin on the ovary and its possible mechanisms. Female C57BL/6 mice of 27-week old were divided into two groups, the control group (CON) and metformin-treated group (MET). CON mice were fed ad libitum, while MET mice were fed on chows supplied with 100mg/kg metformin for half a year. Ovarian reserve and function were assessed by ovarian follicle counts, estrous cycle and sex hormones levels. The expressions of oxidized metabolites, such as 8-hydroxy-2´-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), and ovarian aging associated proteins P16, SIRT1, p-rpS6 and Bcl2 were examined. The MET mice exhibited increased level of serum E2 hormone and higher percentage of regular estrous cycles after 6 months' feeding, compared to the CON mice. The amount of primordial and primary follicles and the expression of SIRT1 were significantly increased, but the levels of P16, 8-OHdG, 4-HNE and p-rpS6 were decreased in the MET mice. These results indicate that metformin can delay ovarian aging process, probably by inducing the expression of SIRT1 and reducing the oxidative damage.
KEYWORDS:
SIRT1; metformin; ovarian aging; oxidative stress

When battling high blood cholesterol, white meat is no better than red meat, study says
Research followed 113 people on controlled diets to garner results contradicting conventional wisdom
CBC News · Posted: Jun 11, 2019
https://www.cbc.ca/news/health/health-white-meat-red-meat-cholesterol-science-1.5168534
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Effects of red meat, white meat, and nonmeat protein sources on atherogenic lipoprotein measures in the context of low compared with high saturated fat intake: a randomized controlled trial.
Bergeron N, Chiu S, Williams PT, M King S, Krauss RM.
Am J Clin Nutr. 2019 Jun 4. pii: nqz035. doi: 10.1093/ajcn/nqz035. [Epub ahead of print]
PMID: 31161217
https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqz035/5494812
https://watermark.silverchair.com/nqz035.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAlAwggJMBgkqhkiG9w0BBwagggI9MIICOQIBADCCAjIGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMasb8QHNzeTgS8ccEAgEQgIICA_Q13ymYNFRljhS_NilkiErxI_SnuwbC6-7bcNiI3G2ShO_WGAql0vw2STPzEIXbB8ek9S37-RUXiP6z57B200jGbv-bl_EouHSOlvmMfvUQ2FbI_xmH84LfEf5f8h-Mv7m65RSEzTrGWZptlaX84Pko0_ql_97PB7rswTGtjchY6mWvxVmtjjLfANuAYgoxAdktXbFenbmVFskpn7W5MgqNwnlby-jRUtv03k2zhWGv98i9RSLMwlBa8bebzlDDe7eXIjuPCaM6h1kI9WuEhbGGseGNZAHxJpm3wcbXkJnlNZnR7Pg44aUsOT8c8j7tQPlfXLEA7EYTeIzBS4tXzETuCtiHQeVi1OtUTNSC83MIGWExclAk-SlsadFzwPurlkwqrTYmkBlCM07veK0rYWQgLiwttd_y7bKpSe6DdxZx15i7NrjnbIGMXidb8zMib8hoeSEHTdhwPuyZRmmeuUqyIZFjtnR0FRkAm-0HGuab4HPlQNZLDCX1EFeiaxImlDy2kCNj9hyhJnXWU_G4vpeIjU8_ZVezuibK1ib8N0pkVNo9EwvldyNCsF_tA6lSvkgIoR7KzqroLrm9sP5nYEnbRHhjipUzRM2WOJj-nYSEgZmW86y75X-b6zwDbZFQYNGJv3KylQrtC6hV6cVNG1cHEL1EyZxN5rvDbTJmOhombhvf
Abstract
BACKGROUND:
Dietary recommendations to limit red meat are based on observational studies linking intake to cardiovascular disease (CVD) risk together with the potential of its saturated fatty acid (SFA) content to raise low-density lipoprotein (LDL) cholesterol. However, the relation of white meat to CVD risk, and the effects of dietary protein source on lipoprotein particle subfractions, have not been extensively evaluated.
OBJECTIVE:
We tested whether levels of atherogenic lipids and lipoproteins differed significantly following consumption of diets with high red meat content compared with diets with similar amounts of protein derived from white meat or nonmeat sources, and whether these effects were modified by concomitant intake of high compared with low SFAs.
METHODS:
Generally healthy men and women, 21-65 y, body mass index 20-35 kg/m2, were randomly assigned to 1 of 2 parallel arms (high or low SFA) and within each, allocated to red meat, white meat, and nonmeat protein diets consumed for 4 wk each in random order. The primary outcomes were LDL cholesterol, apolipoprotein B (apoB), small + medium LDL particles, and total/high-density lipoprotein cholesterol.
RESULTS:
Analysis included participants who completed all 3 dietary protein assignments (61 for high SFA; 52 for low SFA). LDL cholesterol and apoB were higher with red and white meat than with nonmeat, independent of SFA content (P < 0.0001 for all, except apoB: red meat compared with nonmeat [P = 0.0004]). This was due primarily to increases in large LDL particles, whereas small + medium LDL and total/high-density lipoprotein cholesterol were unaffected by protein source (P = 0.10 and P = 0.51, respectively). Primary outcomes did not differ significantly between red and white meat. Independent of protein source, high compared with low SFA increased LDL cholesterol (P = 0.0003), apoB (P = 0.0002), and large LDL (P = 0.0002).
CONCLUSIONS:
The findings are in keeping with recommendations promoting diets with a high proportion of plant-based food but, based on lipid and lipoprotein effects, do not provide evidence for choosing white over red meat for reducing CVD risk. This trial was registered at Clinicaltrials.gov as NCT01427855.
KEYWORDS:
beef; chicken; dairy fat; dietary recommendations; lipoprotein particle distribution; plant protein; poultry; vegetable protein

[AlPater]

Time-restricted feeding delays the emergence of the age-associated, neoplastic-prone tissue landscape.
Serra M, Marongiu F, Pisu MG, Serra M, Laconi E.
Aging (Albany NY). 2019 Jun 12. doi: 10.18632/aging.102021. [Epub ahead of print]
PMID: 31188781
https://s3-us-west-1.amazonaws.com/paperchase-aging/pdf/dxZSX3zGcxpqLhW4T.pdf
Abstract
Aging increases the risk of cancer partly through alterations in the tissue microenvironment. Time-restricted feeding (TRF) is being proposed as an effective strategy to delay biological aging. In the present studies, we assessed the effect of long-term exposure to TRF on the emergence of the age-associated, neoplastic-prone tissue landscape. Animals were exposed to either ad libitum feeding (ALF) or TRF for 18 months and then transplanted with hepatocytes isolated from pre-neoplastic nodules. Both groups were continued ALF and the growth of transplanted cells was evaluated 3 months later. A significant decrease in frequency of larger size clusters of pre-neoplastic hepatocytes was seen in TRF-exposed group compared to controls. Furthermore, TRF modified several parameters related to both liver and systemic aging towards the persistence of a younger phenotype, including a decrease in liver cell senescence, diminished fat accumulation and up-regulation of SIRT1 in the liver, down-regulation of plasma IGF-1, decreased levels of plasma lipoproteins and up-regulation of hippocampal brain-derived growth factor (BDNF).These results indicate that TRF was able to delay the onset of the neoplastic-prone tissue landscape typical of aging. To our knowledge, this is the first investigation to describe a direct beneficial effect of TRF on early phases of carcinogenesis.
KEYWORDS:
aging; carcinogenesis; time restricted feeding; tissue microenvironment

[AlPater]

Dietary glycemic index, glycemic load, and risk of mortality from all causes and cardiovascular diseases: a systematic review and dose-response meta-analysis of prospective cohort studies.
Shahdadian F, Saneei P, Milajerdi A, Esmaillzadeh A.
Am J Clin Nutr. 2019 Jun 12. pii: nqz061. doi: 10.1093/ajcn/nqz061. [Epub ahead of print]
PMID: 31187856
Abstract
BACKGROUND:
Previous findings on the association of dietary glycemic index (GI) and glycemic load (GL) with mortality are conflicting.
OBJECTIVES:
The aim of this study was to summarize earlier findings on the association between dietary GI and GL and the risk of cardiovascular disease (CVD) and all-cause mortality.
METHODS:
A comprehensive literature search was performed of electronic databases, including MEDLINE (PubMed), Scopus, ISI Web of Science, EMBASE, and Google scholar, up to September 2018. Prospective cohort studies that reported GI and GL as the exposure and all-cause or CVD mortality as the outcome were included in the analysis. The random-effects model was used to estimate pooled RR and 95% CIs of all-cause and CVD mortality.
RESULTS:
Eighteen cohort studies with a total of 251,497 participants, reporting 14,774 cases of all-cause mortality and 3658 cases of CVD mortality, were included in the present analysis. No significant association was found between dietary GI and all-cause mortality (RR: 1.07; 95% CI: 0.96, 1.19) and CVD mortality (RR: 1.02; 95% CI: 0.87, 1.20). In addition, dietary GL was not associated with all-cause mortality (RR: 1.08; 95% CI: 0.93, 1.27) or CVD mortality (RR: 1.07; 95% CI: 0.92, 1.25). However, the highest dietary GI, in comparison to the lowest one, significantly increased the risk of all-cause mortality in women (RR: 1.17; 95% CI: 1.02, 1.35). No evidence for a nonlinear association between dietary GI or GL and all-cause and CVD mortality was found (P > 0.05).
CONCLUSIONS:
This meta-analysis of prospective cohort studies showed no significant association between either dietary GI or GL and all-cause and CVD mortality in men, but a positive association of GI with all-cause mortality in women.
KEYWORDS:
CVD mortality; all-causes mortality; glycemic index; glycemic load; meta-analysis

Adult cancer risk in women who were breastfed as infants: large UK prospective study.
Yang TO, Cairns BJ, Green J, Reeves GK, Floud S, Bradbury KE, Beral V; Million Women Study Collaborators.
Eur J Epidemiol. 2019 Jun 11. doi: 10.1007/s10654-019-00528-z. [Epub ahead of print]
PMID: 31187313
Abstract
There are known short-term benefits in breastfed infants versus bottle-fed infants in terms of lower risks of infection and obesity in infancy and childhood, but the long-term effect on the risk of adult cancers is unclear. In a cohort of 1 in 4 UK women born in 1935-1950 we report the incidence of adult cancers in relation to having been breastfed in infancy. In median year 2001 (interquartile range 2000-2003) 548,741 women without prior cancer reported whether they had been breastfed. There was 81% agreement between women's report of having been breastfed and information on breastfeeding recorded when they were 2 years old. Participants were followed by record-linkage to national cancer registration, hospital admission and death databases. Cox regression yielded adjusted relative risks (RRs) and 95% confidence intervals (CI) by having been breastfed or not for eight cancer sites with > 2000 incident cases and for related conditions, where appropriate. Of the eight cancers examined here one association was highly statistically significant: an increase in colorectal cancer incidence among women who had been breastfed versus not (RR 1.18, 95% CI 1.12-1.24, n = 8651). To investigate further the findings for colorectal cancer, we studied eight other gastro-intestinal conditions, and found increased risks in women who had been breastfed versus not for benign colorectal polyps (RR 1.09, 95% CI 1.05-1.13, n = 17,677) and for appendicitis (RR 1.19, 95% CI 1.07-1.31, n = 2108). The greater risks of adult colorectal cancer, colorectal polyps and appendicitis associated with having been breastfed in infancy suggest possible long-term effects of infant feeding practices on the gastrointestinal tract. Further studies are required to clarify this novel association.
KEYWORDS:
Breast cancer; Breast milk; Colorectal cancer; Infant feeding

[AlPater]

Depressive Disorders and Religious Engagement in Very Old People.
Strinnholm S, Gustafson Y, Niklasson J.
Gerontol Geriatr Med. 2019 May 10;5:2333721419846576. doi: 10.1177/2333721419846576. eCollection 2019 Jan-Dec.
PMID: 31192277
Abstract
Objective: To examine associations between religious engagement and depressive disorders in very old people. Method: This cross-sectional study uses data from the Umeå 85+/Gerontological Regional Database (GERDA) study. Every other 85-year-old, every 90-year-old, and everyone more than 95 years from eight municipalities in northern Sweden and Finland were invited: 1,014 persons accepted participation. Data were gathered using questionnaires and assessment scales during structured home visits. Results: The prevalence of depressive disorders was 35.8%. In a logistic regression model, several factors were adjusted for, such as demographic variables including social factors, diseases, and cognitive and physical functional level. A high level of self-reported religious engagement was independently associated with not having depressive disorders (odds ratio [OR] = 0.58, confidence interval [CI] = [0.38, 0.89]). After stratifying by gender, religious engagement was only significant for women (OR = 0.49, CI = [0.29, 0.82]). Discussion: There is an association between a high level of religious engagement and being free from diagnosis of depressive disorders among very old women.
KEYWORDS:
80 and above; aged; depression; religion; salutogenesis

Up-regulation of FOXO1 and reduced inflammation by β-hydroxybutyric acid are essential diet restriction benefits against liver injury.
Miyauchi T, Uchida Y, Kadono K, Hirao H, Kawasoe J, Watanabe T, Ueda S, Okajima H, Terajima H, Uemoto S.
Proc Natl Acad Sci U S A. 2019 Jun 13. pii: 201820282. doi: 10.1073/pnas.1820282116. [Epub ahead of print]
PMID: 31196960
Abstract
Liver ischemia and reperfusion injury (IRI) is a major challenge in liver surgery. Diet restriction reduces liver damage by increasing stress resistance; however, the underlying molecular mechanisms remain unclear. We investigated the preventive effect of 12-h fasting on mouse liver IRI. Partial warm hepatic IRI model in wild-type male C57BL/6 mice was used. The control ischemia and reperfusion (IR) group of mice was given food and water ad libitum, while the fasting IR group was given water but not food for 12 h before ischemic insult. In 12-h fasting mice, serum liver-derived enzyme level and tissue damages due to IR were strongly suppressed. Serum β-hydroxybutyric acid (BHB) was significantly raised before ischemia and during reperfusion. Up-regulated BHB induced an increment in the expression of FOXO1 transcription factor by raising the level of acetylated histone. Antioxidative enzyme heme oxigenase 1 (HO-1), a target gene of FOXO1, then increased. Autophagy activity was also enhanced. Serum high-mobility group box 1 was remarkably lowered by the 12-h fasting, and activation of NF-κB and NLRP3 inflammasome was suppressed. Consequently, inflammatory cytokine production and liver injury were reduced. Exogenous BHB administration or histone deacetylase inhibitor administration into the control fed mice ameliorated liver IRI, while FOXO1 inhibitor administration to the 12-h fasting group exacerbated liver IRI. The 12-h fasting exerted beneficial effects on the prevention of liver IRI by increasing BHB, thus up-regulating FOXO1 and HO-1, and by reducing the inflammatory responses and apoptotic cell death via the down-regulation of NF-κB and NLRP3 inflammasome.
KEYWORDS:
FOXO1; fasting; ischemia and reperfusion injury; β-hydroxybutyric acid

Dietary Glycemic Index and Load and the Risk of Type 2 Diabetes: A Systematic Review and Updated Meta-Analyses of Prospective Cohort Studies.
Livesey G, Taylor R, Livesey HF, Buyken AE, Jenkins DJA, Augustin LSA, Sievenpiper JL, Barclay AW, Liu S, Wolever TMS, Willett WC, Brighenti F, Salas-Salvadó J, Björck I, Rizkalla SW, Riccardi G, La Vecchia C, Ceriello A, Trichopoulou A, Poli A, Astrup A, Kendall CWC, Ha MA, Baer-Sinnott S, Brand-Miller JC.
Nutrients. 2019 Jun 5;11(6). pii: E1280. doi: 10.3390/nu11061280. Review.
PMID: 31195724
Abstract
Published meta-analyses indicate significant but inconsistent incident type-2 diabetes(T2D)-dietary glycemic index (GI) and glycemic load (GL) risk ratios or risk relations (RR). It is nowover a decade ago that a published meta-analysis used a predefined standard to identify validstudies. Considering valid studies only, and using random effects dose-response meta-analysis(DRM) while withdrawing spurious results (p < 0.05), we ascertained whether these relationswould support nutrition guidance, specifically for an RR > 1.20 with a lower 95% confidence limit>1.10 across typical intakes (approximately 10th to 90th percentiles of population intakes). Thecombined T2D-GI RR was 1.27 (1.15-1.40) (p < 0.001, n = 10 studies) per 10 units GI, while that forthe T2D-GL RR was 1.26 (1.15-1.37) (p < 0.001, n = 15) per 80 g/d GL in a 2000 kcal (8400 kJ) diet.The corresponding global DRM using restricted cubic splines were 1.87 (1.56-2.25) (p < 0.001, n =10) and 1.89 (1.66-2.16) (p < 0.001, n = 15) from 47.6 to 76.1 units GI and 73 to 257 g/d GL in a 2000kcal diet, respectively. In conclusion, among adults initially in good health, diets higher in GI or GLwere robustly associated with incident T2D. Together with mechanistic and other data, thissupports that consideration should be given to these dietary risk factors in nutrition advice.Concerning the public health relevance at the global level, our evidence indicates that GI and GLare substantial food markers predicting the development of T2D worldwide, for persons ofEuropean ancestry and of East Asian ancestry.
KEYWORDS:
alcohol; cohort studies; dietary fiber; epidemiology; glycemic index; glycemic load; meta-analysis; protein; type 2 diabetes

Aspirin for Primary Prevention of Cardiovascular Events.
Abdelaziz HK, Saad M, Pothineni NVK, Megaly M, Potluri R, Saleh M, Kon DLC, Roberts DH, Bhatt DL, Aronow HD, Abbott JD, Mehta JL.
J Am Coll Cardiol. 2019 Jun 18;73(23):2915-2929. doi: 10.1016/j.jacc.2019.03.501.
PMID: 31196447
Abstract
BACKGROUND:
The efficacy and safety of aspirin for primary prevention of cardiovascular disease (CVD) remain debatable.
OBJECTIVES:
The purpose of this study was to examine the clinical outcomes with aspirin for primary prevention of CVD after the recent publication of large trials adding >45,000 individuals to the published data.
METHODS:
Randomized controlled trials comparing clinical outcomes with aspirin versus control for primary prevention with follow-up duration of ≥1 year were included. Efficacy outcomes included all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stroke, transient ischemic attack (TIA), and major adverse cardiovascular events. Safety outcomes included major bleeding, intracranial bleeding, fatal bleeding, and major gastrointestinal (GI) bleeding. Random effects DerSimonian-Laird risk ratios (RRs) for outcomes were calculated.
RESULTS:
A total of 15 randomized controlled trials including 165,502 participants (aspirin n = 83,529, control n = 81,973) were available for analysis. Compared with control, aspirin was associated with similar all-cause death (RR: 0.97; 95% confidence interval [CI]: 0.93 to 1.01), CV death (RR: 0.93; 95% CI: 0.86 to 1.00), and non-CV death (RR: 0.98; 95% CI: 0.92 to 1.05), but a lower risk of nonfatal MI (RR: 0.82; 95% CI: 0.72 to 0.94), TIA (RR: 0.79; 95% CI: 0.71 to 0.89), and ischemic stroke (RR: 0.87; 95% CI: 0.79 to 0.95). Aspirin was associated with a higher risk of major bleeding (RR: 1.5; 95% CI: 1.33 to 1.69), intracranial bleeding (RR: 1.32; 95% CI: 1.12 to 1.55), and major GI bleeding (RR: 1.52; 95% CI: 1.34 to 1.73), with similar rates of fatal bleeding (RR: 1.09; 95% CI: 0.78 to 1.55) compared with the control subjects. Total cancer and cancer-related deaths were similar in both groups within the follow-up period of the study.
CONCLUSIONS:
Aspirin for primary prevention reduces nonfatal ischemic events but significantly increases nonfatal bleeding events.
KEYWORDS:
aspirin; cardiovascular events; primary prevention

Association of changes in red meat consumption with total and cause specific mortality among US women and men: two prospective cohort studies.
Zheng Y, Li Y, Satija A, Pan A, Sotos-Prieto M, Rimm E, Willett WC, Hu FB.
BMJ. 2019 Jun 12;365:l2110. doi: 10.1136/bmj.l2110.
PMID: 31189526 Free Article
https://www.bmj.com/content/bmj/365/bmj.l2110.full.pdf
Abstract
OBJECTIVE:
To evaluate the association of changes in red meat consumption with total and cause specific mortality in women and men.
DESIGN:
Two prospective cohort studies with repeated measures of diet and lifestyle factors.
SETTING:
Nurses' Health Study and the Health Professionals Follow-up Study, United States.
PARTICIPANTS:
53 553 women and 27 916 men without cardiovascular disease or cancer at baseline.
MAIN OUTCOME MEASURE:
Death confirmed by state vital statistics records, the national death index, or reported by families and the postal system.
RESULTS:
14 019 deaths occurred during 1.2 million person years of follow-up. Increases in red meat consumption over eight years were associated with a higher mortality risk in the subsequent eight years among women and men (both P for trend<0.05, P for heterogeneity=0.97). An increase in total red meat consumption of at least half a serving per day was associated with a 10% higher mortality risk (pooled hazard ratio 1.10, 95% confidence interval 1.04 to 1.17). For processed and unprocessed red meat consumption, an increase of at least half a serving per day was associated with a 13% higher mortality risk (1.13, 1.04 to 1.23) and a 9% higher mortality risk (1.09, 1.02 to 1.17), respectively. A decrease in consumption of processed or unprocessed red meat of at least half a serving per day was not associated with mortality risk. The association between increased red meat consumption and mortality risk was consistent across subgroups defined by age, physical activity, dietary quality, smoking status, or alcohol consumption.
CONCLUSION:
Increases in red meat consumption, especially processed meat, were associated with higher overall mortality rates.

Body mass index and risk of inflammatory bowel disease: A systematic review and dose-response meta-analysis of cohort studies of over a million participants.
Rahmani J, Kord-Varkaneh H, Hekmatdoost A, Thompson J, Clark C, Salehisahlabadi A, Day AS, Jacobson K.
Obes Rev. 2019 Jun 12. doi: 10.1111/obr.12875. [Epub ahead of print] Review.
PMID: 31190427
Abstract
The relationship between body mass index (BMI) and risk of inflammatory bowel disease (IBD) is controversial. We performed a dose-response meta-analysis to investigate the association between BMI and risk of incident ulcerative colitis (UC) and Crohn's disease (CD) using prospective cohort studies. A systematic search was conducted in MEDLINE/PubMed, SCOPUS, Cochrane, and Web of Science databases from inception to January 2019. DerSimonian and Laird random-effects model was used to estimate combined hazard ratios (HRs). Overall, 882 articles were screened, and 42 full-text articles were reviewed for inclusion using the study eligibility criteria. Five studies evaluated the association between BMI and IBD with 1 044 517 participants. Pooled results showed a significant association between participants affected by obesity and risk of CD (HR: 1.42, 95% CI: 1.18-1.71, I2 : 0.00). There was a significant nonlinear association between BMI and risk of CD (P = .01, coeff = 0.5024). Pooled results did not show any significant association between being underweight and risk of UC (HR: 1.07, 95% CI: 0.96-1.19, I2 : 0.00) or CD (HR: 1.11, 95% CI: 0.93-1.31, I2 : 12.8). There was no difference in the risk for UC among participants affected by obesity compared with participants categorized as having normal BMI (HR: 0.96, 95% CI: 0.80-1.14, I2 : 8.0). This systematic review and meta-analysis identified significant dose-response relationship between being affected by obesity, as a risk factor, and incidence of CD.
KEYWORDS:
Crohn's disease; body mass index; inflammatory bowel disease; ulcerative colitis

Serum Sodium and Pulse Pressure in SPRINT.
Nowak KL, Chonchol M, Jovanovich A, You Z, Bates J, Foy C, Glasser S, Killeen AA, Kostis J, Rodriguez CJ, Segal M, Simmons DL, Taylor A, Lovato LC, Ambrosius WT, Supiano MA; SPRINT Research Group.
Am J Hypertens. 2019 Jun 11;32(7):649-656. doi: 10.1093/ajh/hpz055.
PMID: 30977767
https://academic.oup.com/ajh/article/32/7/649/5449002
Abstract
BACKGROUND:
High dietary sodium intake may induce a small, yet physiologically relevant rise in serum sodium concentration, which associates with increased systolic blood pressure. Cellular data suggest that this association is mediated by increased endothelial cell stiffness. We hypothesized that higher serum sodium levels were associated with greater arterial stiffness in participants in the Systolic Blood Pressure Intervention Trial (SPRINT).
METHODS:
Multivariable linear regression was used to examine the association between baseline serum sodium level and (i) pulse pressure (PP; n = 8,813; a surrogate measure of arterial stiffness) and (ii) carotid-femoral pulse wave velocity (CFPWV; n = 591 in an ancillary study to SPRINT).
RESULTS:
Baseline mean ± SD age was 68 ± 9 years and serum sodium level was 140 ± 2 mmol/L. In the PP analysis, higher serum sodium was associated with increased baseline PP in the fully adjusted model (tertile 3 [≥141 mmol] vs. tertile 2 [139-140 mmol]; β = 0.87, 95% CI = 0.32 to 1.43). Results were similar in those with and without chronic kidney disease. In the ancillary study, higher baseline serum sodium was not associated with increased baseline CFPWV in the fully adjusted model (β = 0.35, 95% CI = -0.14 to 0.84).
CONCLUSIONS:
Among adults at high risk for cardiovascular events but free from diabetes, higher serum sodium was independently associated with baseline arterial stiffness in SPRINT, as measured by PP, but not by CFPWV. These results suggest that high serum sodium may be a marker of risk for increased PP, a surrogate index of arterial stiffness.
KEYWORDS:
CKD; blood pressure; electrolyte imbalances; hypernatremia; hypertension; pulse pressure; pulse-wave velocity

Effects of ad libitum consumed, low-fat, high-fiber plant-based diet supplemented with plant-based meal replacements on cardiovascular risk factors.
Jakše B, Jakše B, Pajek J, Pajek M.
Food Nutr Res. 2019 May 21;63. doi: 10.29219/fnr.v63.1560. eCollection 2019.
PMID: 31191190
Abstract
BACKGROUND:
Sustainable nutritional strategies to reduce risk factors of cardiovascular diseases are highly needed. Inclusion of meal replacements may increase adherence to plant-based diets (PBDs).
OBJECTIVE:
The aim of this study was to test the effects of a transition from a western-type diet to a new nutritional paradigm with a PBD from predominately unrefined whole food sources, eaten ad libitum and including nutrient-enriched plant-based meal replacements twice daily.
DESIGN:
This was a single-arm, prospective interventional trial for 10 weeks in 36 participants with extension to 36 weeks in 18 participants. The main endpoint was serum low-density lipoprotein (LDL)-cholesterol measured at baseline, after 10 weeks (phase 1), and after 36 weeks (phase 2). Secondary endpoints included total, non-high-density lipoprotein (HDL) and HDL-cholesterol, fasting glucose, uric acid, and insulin-like growth factor-1 (IGF-1).
RESULTS:
The mean reduction in LDL-cholesterol was 0.6 (95% confidence interval [CI], 0.3-0.8) mmol/L (-15%, P < 0.001) at the end of phase 1, with no further change by the end of phase 2. Similar reductions were noted for non-HDL-cholesterol and total cholesterol. HDL-cholesterol was reduced by 0.16 mmol/L (95% CI, 0.1-0.2). There was a borderline reduction in fasting glucose (5.2 to 5 mmol/L in phase 1, P = 0.08) and a small significant rise in serum uric acid levels of 15 (95% CI, 1-28) μmol/L, P < 0.05. Median baseline value for IGF-1 concentration was 156 μg/L. Participants with baseline IGF-1 below median had a significant increase in IGF-1 value from baseline 110 ± 31 to 132 ± 39 at the end of phase 1 (mean change of +22 μg/L, 95% CI, 11-33, P = 0.001). Participants with baseline IGF-1 above median had no significant change in IGF-1. Significant reductions in body weight, body fat, and visceral fat were observed.
CONCLUSIONS:
Supplemented, unrefined PBD eaten ad libitum was effective in improving total and LDL-cholesterol, non-HDL-cholesterol, and IGF-1 in low baseline IGF-1 subgroup.
KEYWORDS:
atherosclerosis; cholesterol; fat; nutrition; obesity; weight reduction

Total Fermented Dairy Food Intake Is Inversely Associated with Cardiovascular Disease Risk in Women.
Buziau AM, Soedamah-Muthu SS, Geleijnse JM, Mishra GD.
J Nutr. 2019 Jun 13. pii: nxz128. doi: 10.1093/jn/nxz128. [Epub ahead of print]
PMID: 31192363
Abstract
BACKGROUND:
The relation between fermented dairy consumption and type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in an Australian population remains to be established.
OBJECTIVES:
The aim of this study was to investigate the association between fermented dairy consumption and T2DM and CVD risk.
METHODS:
The Australian Longitudinal Study on Women's Health included Australian women (aged 45-50 y) at baseline in 2001, who were followed up through 5 surveys until 2016. Dietary intake was assessed through the use of a validated 101-item FFQ at baseline. Main study outcomes were self-reported physician-diagnosed T2DM and CVD. Logistic regression models adjusted for sociodemographic and lifestyle factors were used to estimate the association between dairy intake and T2DM and CVD risk.
RESULTS:
Of 7633 women free of diabetes at baseline, 701 (9.2%) developed T2DM during a maximum 15-y follow-up period. Women in the highest tertile of yogurt intake had lower adjusted odds of T2DM than those in the lowest tertile (OR: 0.81; 95% CI: 0.67, 0.99; P = 0.041). This relation became nonsignificant after adjustment for dietary variables and total energy intake (OR: 0.88; 95% CI: 0.71, 1.08; P = 0.21). Of 7679 women free of CVD at baseline, 835 (10.9%) cases of CVD were reported during follow-up. High intake of yogurt and total fermented dairy was associated with lower CVD risk (OR: 0.84; 95% CI: 0.70, 1.00; P = 0.05, 0.80; 0.67, 0.96; 0.017, respectively) than observed in the lowest tertile of dairy product intake. Additional adjustment attenuated the relation (OR: 0.87; 95% CI: 0.72, 1.04; P = 0.13, 0.83; 0.69, 1.00; 0.048, for yogurt and total fermented dairy, respectively). No associations were found with other dairy groups.
CONCLUSION:
The findings from this population-based study of Australian women suggest an inverse association between total fermented dairy intake and CVD risk, which may partly be accounted for by other dietary components.
KEYWORDS:
Australia; cardiovascular disease; cheese; coronary heart disease; dairy; fermented dairy; stroke; type 2 diabetes mellitus; women's health; yogurt

Effects of dietary and physical activity interventions on the risk of type 2 diabetes in South Asians: meta-analysis of individual participant data from randomised controlled trials.
Jenum AK, Brekke I, Mdala I, Muilwijk M, Ramachandran A, Kjøllesdal M, Andersen E, Richardsen KR, Douglas A, Cezard G, Sheikh A, Celis-Morales CA, Gill JMR, Sattar N, Bhopal RS, Beune E, Stronks K, Vandvik PO, van Valkengoed IGM.
Diabetologia. 2019 Jun 15. doi: 10.1007/s00125-019-4905-2. [Epub ahead of print] Review.
PMID: 31201437
Abstract
AIMS/HYPOTHESIS:
Individuals of South Asian origin have a high risk of type 2 diabetes and of dying from a diabetes-attributable cause. Lifestyle modification intervention trials to prevent type 2 diabetes in high-risk South Asian adults have suggested more modest effects than in European-origin populations. The strength of the evidence of individual studies is limited, however. We performed an individual participant data meta-analysis of available RCTs to assess the effectiveness of lifestyle modification in South Asian populations worldwide.
METHODS:
We searched PubMed, EMBASE, Cochrane Library and Web of Science (to 24 September 2018) for RCTs on lifestyle modification interventions incorporating diet and/or physical activity in South Asian adults. Reviewers identified eligible studies and assessed the quality of the evidence. We obtained individual participant data on 1816 participants from all six eligible trials (four from Europe and two from India). We generated HR estimates for incident diabetes (primary outcome) and mean differences for fasting glucose, 2 h glucose, weight and waist circumference (secondary outcomes) using mixed-effect meta-analysis overall and by pre-specified subgroups. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to rate the quality of evidence of the estimates. The study is registered with the International Prospective Register of Systematic Reviews ([PROSPERO] CRD42017078003).
RESULTS:
Incident diabetes was observed in 12.6% of participants in the intervention groups and in 20.0% of participants in the control groups. The pooled HR for diabetes incidence was 0.65 (95% CI 0.51, 0.81; I2 = 0%) in intervention compared with control groups. The absolute risk reduction was 7.4% (95% CI 4.0, 10.2), with no interactions for the pre-specified subgroups (sex, BMI, age, study duration and region where studies were performed). The quality of evidence was rated as moderate. Mean difference for lifestyle modification vs control groups for 2 h glucose was -0.34 mmol/l (95% CI -0.62, -0.07; I2 = 50%); for weight -0.75 kg (95% CI -1.34, -0.17; I2 = 71%) and for waist -1.16 cm (95% CI -2.16, -0.16; I2 = 75%). No effect was found for fasting glucose. Findings were similar across subgroups, except for weight for European vs Indian studies (-1.10 kg vs -0.08 kg, p = 0.02 for interaction).
CONCLUSIONS/INTERPRETATION:
Despite modest changes for adiposity, lifestyle modification interventions in high-risk South Asian populations resulted in a clinically important 35% relative reduction in diabetes incidence, consistent across subgroups. If implemented on a large scale, lifestyle modification interventions in high-risk South Asian populations in Europe would reduce the incidence of diabetes in these populations.
KEYWORDS:
Diet; Individual participant data meta-analysis; Lifestyle intervention; Physical activity; Prevention; RCT; South Asians; Type 2 diabetes