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

[AlPater]

Dairy product consumption and development of cancer: an overview of reviews.
Jeyaraman MM, Abou-Setta AM, Grant L, Farshidfar F, Copstein L, Lys J, Gottschalk T, Desautels D, Czaykowski P, Pitz M, Zarychanski R.
BMJ Open. 2019 Jan 25;9(1):e023625. doi: 10.1136/bmjopen-2018-023625.
PMID: 30782711 Free Article
https://bmjopen.bmj.com/content/bmjopen/9/1/e023625.full.pdf
Abstract
OBJECTIVES:
To provide a comprehensive systematic overview of current evidence from pooled analyses/meta-analyses and systematic reviews (PMASRs) pertaining to dairy consumption and incident cancer and/or all-cause or cancer-specific mortality.
DESIGN:
Overview of reviews.
SETTING:
Community setting.
PARTICIPANTS:
The unit of analysis is PMASRs. A total of 42 PMASRs was included in this overview of reviews.
INTERVENTIONS/EXPOSURES:
Any dairy product consumption (eg, milk, yogurt, etc).
PRIMARY AND SECONDARY OUTCOMES MEASURES:
Primary outcome measure is development of any type of cancer. Secondary outcome measures are all-cause mortality and cancer-specific mortality.
RESULTS:
From 9693 citations identified, we included 42 PMASRs (52 study reports) published between 1991 and 2017. Thirty-one (74%) of these was pooled analyses/meta analyses, and only 11 (26%) were systematic reviews and meta-analyses. There was a wide variability in the type of study designs included within the other PMASRs, thus contributing to variable and, in instances, divergent estimates of cancer risk for several cancer subtypes. For example, only one systematic review and meta-analysis exclusively included prospective study designs. Most PMASRs were of low to moderate quality based on the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) scores. The median AMSTAR score was 5 (IQR 2-7). Our overview identified conflicting evidence from PMASRs on association between dairy consumption and incident cancers or mortality. Heterogeneity in summary estimates reflected the inclusion of variable study designs and overall low methodological quality of individual PMASRs.
CONCLUSIONS:
The association between dairy consumption and cancer risk has been explored in PMASRs with a variety of study designs and of low to moderate quality. To fully characterise valid associations between dairy consumption and risk of cancer and/or mortality rigorously conducted, PMASRs including only high-quality prospective study designs are required.
KEYWORDS:
cancer; dairy; dairy products; overview of reviews

Caffeinated and decaffeinated coffee consumption and risk of all-cause mortality: a dose-response meta-analysis of cohort studies.
Li Q, Liu Y, Sun X, Yin Z, Li H, Cheng C, Liu L, Zhang R, Liu F, Zhou Q, Wang C, Li L, Wang B, Zhao Y, Zhang M, Hu D.
J Hum Nutr Diet. 2019 Feb 20. doi: 10.1111/jhn.12633. [Epub ahead of print] Review.
PMID: 30786114
https://sci-hub.tw/10.1111/jhn.12633
Abstract
BACKGROUND:
Previous meta-analysis showed an inverse association between coffee consumption and all-cause mortality. However, the relationship between caffeinated and decaffeinated coffee consumption and all-cause mortality is inconsistent. We aimed to identify and review the published evidence updating the association between coffee consumption and all-cause mortality and, furthermore, to investigate the association of caffeinated and decaffeinated coffee consumption and all-cause mortality.
METHODS:
We systematically searched PubMed and Web of Science for studies published up to 9 November 2017. Cohort studies in which authors reported relative risks (RRs) of all-cause mortality for at least three levels of coffee consumption were eligible. Random-effects models were used to estimate the pooled RR of all-cause mortality with coffee consumption. Restricted cubic splines were used to model the dose-response association.
RESULTS:
We included 21 cohort study articles (10 103 115 study participants and 240 303 deaths). We found a nonlinear association between coffee consumption and all-cause mortality (Pnonlinearity  < 0.001). Compared with no or rare coffee consumption, with a consumption of 3 cups day-1 , the risk of all-cause mortality might reduce 13% (RR = 0.87; 95% confidence interval = 0.84-0.89).
CONCLUSIONS:
The findings of the present study provide quantitative data suggesting that coffee consumption plays a role in reducing the risk of all-cause mortality. Similar inverse associations are found for caffeinated coffee and decaffeinated coffee.
KEYWORDS:
all-cause mortality; coffee; cohort studies; dose-response meta-analysis

Does Kidney Longevity Mean Healthy Vegan Food and Less Meat or Is Any Low-Protein Diet Good Enough?
Kalantar-Zadeh K, Moore LW.
J Ren Nutr. 2019 Mar;29(2):79-81. doi: 10.1053/j.jrn.2019.01.008. No abstract available.
PMID: 30782404
https://sci-hub.tw/10.1053/j.jrn.2019.01.008

[AlPater]

Maintenance of skeletal muscle function following reduced daily physical activity in healthy older adults: a pilot trial.
Oikawa SY, Callahan DM, McGlory C, Toth MJ, Phillips SM.
Appl Physiol Nutr Metab. 2019 Feb 22. doi: 10.1139/apnm-2018-0631. [Epub ahead of print]
PMID: 30794431
Abstract
INTRODUCTION:
Older adults can experience periods of inactivity related to disease or illness, which can hasten the development of physical disability, in part, through reductions in skeletal muscle strength and power. To date no study has characterized adaptations in skeletal muscle physical function in response to reduced daily physical activity.
METHODS:
Participants (15 men, 69±2 years, 15 women, 68±4 years) restricted their daily steps (<750steps/d, SR) while being energy restricted (ER, -500kcal/d) for 2wks before returning to normal activity levels during recovery (RC, 1wk). Before and after each phase, measures of knee extensor isometric maximum voluntary contraction (MVC), time-to-peak torque (TTPT), and physical function were performed and muscle biopsies were taken from a subset of participants.
RESULTS:
Following the energy restriction and step-reduction phase (ER+SR), MVC was reduced by 9.1 and 6.1 Nm in men and women respectively (p = 0.02), which returned to baseline after RC in men, but not women (p = 0.046). Tmax (maximum isometric tension) in MHC IIA fibres (p<0.01) and Pmax (maximum power production) in MHC I and IIA (p = 0.05) were increased by 14%, 25%, and 10% respectively following ER+SR. Reductions in muscle strength could not be explained by changes in single muscle fibre function in a sub-sample (n=9 men) of volunteers.
DISCUSSION:
These data highlight the resilience of physical function in healthy older men in the face of an acute period of ER+SR and demonstrate sex-based differences in the ability to recover muscle strength upon resumption of physical activity.

Skeletal Muscle Mass as a Mortality Predictor among Nonagenarians and Centenarians: A Prospective Cohort Study.
Wang H, Hai S, Liu Y, Liu Y, Dong B.
Sci Rep. 2019 Feb 20;9(1):2420. doi: 10.1038/s41598-019-38893-0.
PMID: 30787413
Abstract
This study aimed to evaluate the association between skeletal muscle mass and long-term all-cause mortality among nonagenarians and centenarians in China. We used data from the Project of Longevity and Aging in Dujiangyan (PLAD). A total of 738 community-dwelling people aged ≥ 90 years (mean age of 93.5 ± 3.2 years) were analyzed in this study. The appendicular skeletal muscle mass (ASM) was estimated using a previously validated anthropometric equation. The information on the survival status was requested from the local government registries during the 4 year follow-up period following the baseline investigation. The mean muscle mass index (SMI) was 6.11 ± 0.53 kg/m2 in men and 4.00 ± 0.63 kg/m2 in women, respectively. Low muscle mass was associated with a higher risk of death (hazard ratio

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1.54; (95% confidence interval [CI]:1.10-2.16) in women; however, no significant association was found in men. Disability in activities of daily living (ADL) (HR = 1.73; 95% CI: 1.13-2.63) in men and women and cognitive impairment (HR = 1.49; 95% CI: 1.05-2.13) in men were also associated with increased all-cause mortality. In conclusion, low muscle mass were predictors of long-term mortality in nonagenarian and centenarian women.

Effects of L-citrulline supplementation on blood pressure: A systematic review and meta-analysis.
Barkhidarian B, Khorshidi M, Shab-Bidar S, Hashemi B.
Avicenna J Phytomed. 2019 Jan-Feb;9(1):10-20. Review.
PMID: 30788274
Abstract
OBJECTIVE:
We aimed to conduct a systematic review and meta-analysis of clinical trials that examined the effects of L-citrulline supplementation on blood pressure (BP).
MATERIALS AND METHODS:
We searched MEDLINE, SCOPUS, PUBMED and Google scholar databases from inception to November 16, 2017 and 811 papers were identified, of which 8 trials with 10 data sets met the inclusion criteria. Inclusion criteria were: (1) application of randomized clinical trial with either crossover or parallel designs; (2) studies conducted in adults (≥18 y); (3) oral supplementation with L-citrulline compared to control group; (4) expression of sufficient data about systolic and diastolic BP at baseline and at the end of the study in each group. BP effects were pooled by random-effects models, with trials weighted by inverse variance.
RESULTS:
The included studies' sample size ranged between 12 and 34 subjects. The mean age of the participants in these trials ranged between 22 and 71 years. Dosage of L-citrulline supplementation varied from 3 to 9 g/day. Duration of the intervention ranged between 1 and 17 weeks. The pooled changes in systolic and diastolic BP were (MD, -4.10 mm Hg; 95% CI [-7.94, -0.26]; p=0.037) and (MD -2.08 mm Hg; 95% CI [-4.32, 0.16]; P=0.069), respectively. The subgroup analysis showed a significant diastolic BP reduction in studies that used doses of ≥6 g/day (MD -2.75 mm Hg; 95% CI [-5.37, -0.12]; p=0.04).
CONCLUSION:
Our results suggest that L-citrulline supplementation may reduce systolic BP. A significant reduction in diastolic BP was observed only in the studies that used doses ≥ 6 g/day.
KEYWORDS:
Blood pressure; L-citrulline; Supplementation

Ultra-processed food intake and mortality in the USA: results from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994).
Kim H, Hu EA, Rebholz CM.
Public Health Nutr. 2019 Feb 21:1-9. doi: 10.1017/S1368980018003890. [Epub ahead of print]
PMID: 30789115
Abstract
OBJECTIVE:
To evaluate the association between ultra-processed food intake and all-cause mortality and CVD mortality in a nationally representative sample of US adults.
DESIGN:
Prospective analyses of reported frequency of ultra-processed food intake in 1988-1994 and all-cause mortality and CVD mortality through 2011.
SETTING:
The Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994).ParticipantsAdults aged ≥20 years (n 11898).
RESULTS:
Over a median follow-up of 19 years, individuals in the highest quartile of frequency of ultra-processed food intake (e.g. sugar-sweetened or artificially sweetened beverages, sweetened milk, sausage or other reconstructed meats, sweetened cereals, confectionery, desserts) had a 31% higher risk of all-cause mortality, after adjusting for demographic and socio-economic confounders and health behaviours (adjusted hazard ratio=1·31; 95% CI 1·09, 1·58; P-trend = 0·001). No association with CVD mortality was observed (P-trend=0·86).
CONCLUSIONS:
Higher frequency of ultra-processed food intake was associated with higher risk of all-cause mortality in a representative sample of US adults. More longitudinal studies with dietary data reflecting the modern food supply are needed to confirm our results.
KEYWORDS:
Mortality; NOVA classification; Nutritional characteristics; Nutritional quality; Ultra-processed food

Association of Intake of Whole Grains and Dietary Fiber With Risk of Hepatocellular Carcinoma in US Adults.
Yang W, Ma Y, Liu Y, Smith-Warner SA, Simon TG, Chong DQ, Qi Q, Meyerhardt JA, Giovannucci EL, Chan AT, Zhang X.
JAMA Oncol. 2019 Feb 21. doi: 10.1001/jamaoncol.2018.7159. [Epub ahead of print]
PMID: 30789662
https://sci-hub.tw/10.1001/jamaoncol.2018.7159
Abstract
IMPORTANCE:
Increased intake of whole grain and dietary fiber has been associated with lower risk of insulin resistance, hyperinsulinemia, and inflammation, which are known predisposing factors for hepatocellular carcinoma (HCC). Therefore, we hypothesized that long-term intake of whole grains and dietary fiber may be associated with lower risk of HCC.
OBJECTIVE:
To assess the associations of whole grain and dietary fiber intake with the risk of HCC.
DESIGN, SETTING, AND PARTICIPANTS:
Cohort study of the intake of whole grains, their subcomponents (bran and germ), and dietary fiber (cereal, fruit, and vegetable) in 125 455 participants from 2 cohorts from the Nurses' Health Study and the Health Professionals Follow-up Study.
EXPOSURES:
Intake of whole grains, their subcomponents (bran and germ), and dietary fiber (cereal, fruit, and vegetable) were collected and updated almost every 4 years using validated food frequency questionnaires.
MAIN OUTCOMES AND MEASURES:
Multivariable hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression model after adjusting for most known HCC risk factors.
RESULTS:
After an average follow-up of 24.2 years, we identified 141 patients with HCC among 125 455 participants (77 241 women and 48 214 men (mean [SD] age, 63.4 [10.7] years). Increased whole grain intake was significantly associated with lower risk of HCC (the highest vs lowest tertile intake: HR, 0.63; 95% CI, 0.41-0.96; P = .04 for trend). A nonsignificant inverse HCC association was observed for total bran (HR, 0.70; 95% CI, 0.46-1.07; P = .11 for trend), but not for germ. Increased intake of cereal fiber (HR, 0.68; 95% CI, 0.45-1.03; P = .07 for trend), but not fruit or vegetable fiber, was associated with a nonsignificant reduced risk of HCC.
CONCLUSIONS AND RELEVANCE:
Increased intake of whole grains and possibly cereal fiber and bran could be associated with reduced risk of HCC among adults in the United States. Future studies that carefully consider hepatitis B and C virus infections are needed to replicate our findings, to examine these associations in other racial/ethnic or high-risk populations, and to elucidate the underlying mechanisms.

Effects of Vitamin D Supplementation During Pregnancy on Birth Size: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Maugeri A, Barchitta M, Blanco I, Agodi A.
Nutrients. 2019 Feb 20;11(2). pii: E442. doi: 10.3390/nu11020442. Review.
PMID: 30791641
Abstract
During pregnancy, vitamin D supplementation may be a feasible strategy to help prevent low birthweight (LBW) and small for gestational age (SGA) births. However, evidence from randomized controlled trials (RCTs) is inconclusive, probably due to heterogeneity in study design and type of intervention. A systematic literature search in the PubMed-Medline, EMBASE, and Cochrane Central Register of Controlled Trials databases was carried out to evaluate the effects of oral vitamin D supplementation during pregnancy on birthweight, birth length, head circumference, LBW, and SGA. The fixed-effects or random-effects models were used to calculate mean difference (MD), risk ratio (RR), and 95% Confidence Interval (CI). On a total of 13 RCTs, maternal vitamin D supplementation had a positive effect on birthweight (12 RCTs; MD = 103.17 g, 95% CI 62.29⁻144.04 g), length (6 RCTs; MD = 0.22 cm, 95% CI 0.11⁻0.33 cm), and head circumference (6 RCTs; MD:0.19 cm, 95% CI 0.13⁻0.24 cm). In line with these findings, we also demonstrated that maternal vitamin D supplementation reduced the risk of LBW (3 RCTs; RR = 0.40, 95% CI 0.22⁻0.74) and SGA (5 RCTS; RR = 0.69, 95% CI 0.51⁻0.92). The present systematic review and meta-analysis confirmed the well-established effect of maternal vitamin D supplementation on birth size. However, further research is required to better define risks and benefits associated with such interventions and the potential implications for public health.
KEYWORDS:
birth length; birthweight; diet; gestational age; head circumference; nutrition; pregnancy outcomes; vitamin D

Dietary supplement of tomato can accelerate urinary aMT6s level and improve sleep quality in obese postmenopausal women.
Yang TH, Chen YC, Ou TH, Chien YW.
Clin Nutr. 2019 Feb 10. pii: S0261-5614(19)30061-5. doi: 10.1016/j.clnu.2019.02.009. [Epub ahead of print]
PMID: 30792141
https://sci-hub.tw/10.1016/j.clnu.2019.02.009
Abstract
The aim of this study was to investigate the effect of the ingestion of tomato before bed on obese postmenopausal women's urinary 6-sulphatoxymelatonin (aMT6s) level and sleep quality. We quantified melatonin concentrations in beefsteak tomato, black tomato, and two commercial tomato juices and found that beefsteak tomato contained the highest level of melatonin. In this 8-week open-label, randomized controlled dietary intervention trial, 36 subjects completed the entire trial. The tomato group ate 250 g of beefsteak tomatoes 2 h before sleep for 8 weeks. Blood and urine samples were collected at the baseline and in the 8th week and were analyzed. The Pittsburgh Sleep Quality Index (PSQI) in the tomato group significantly decreased with time (p for trend = 0.0297). After 8 weeks of the beefsteak intervention, all components of the PSQI in tomato group had significantly improved, and their aMT6s level was 10-fold significantly higher than that of the control group. Therefore, supplementation with beefsteak tomato before sleep can increase circulating melatonin and improve sleep quality in obese postmenopausal women.
KEYWORDS:
Circadian rhythms; Melatonin; Postmenopausal women; Sleep; Solanum lycopersicum

Sugar-sweetened and artificially-sweetened beverages and changes in cognitive function in the SUN project.
Muñoz-García MI, Martínez-González MA, Martín-Moreno JM, Razquin C, Cervantes S, Guillén-Grima F, Toledo E.
Nutr Neurosci. 2019 Feb 22:1-9. doi: 10.1080/1028415X.2019.1580919. [Epub ahead of print]
PMID: 30794108
Abstract
BACKGROUND:
Sugar-sweetened beverages (SSB) and artificially-sweetened beverages (ASB) have been inconsistently associated with declines in cognitive function. Because of their low caloric content and replacement of sugar, ASB are often seen as 'healthy' alternatives to SSB.
OBJECTIVE:
We longitudinally assessed the association between the consumption of SSB or ASB and cognitive function.
DESIGN:
A subsample of the 'Seguimiento Universidad de Navarra' (SUN) cohort of university graduates aged over 55 years old was evaluated with the Spanish Telephone Interview for Cognitive Status (STICS-m) at two-time points, separated by 6 years. Consumption of SSB and ASB was appraised using a validated food-frequency questionnaire. Linear regression models were fitted, adjusting for potential confounders, including cardiometabolic variables, with the change in the STICS-m score at year 6 as the dependent variable.
RESULTS:
A significant association between the consumption of SSB and changes in cognitive function as measured by the STICS-m was observed in the total sample, with a change of -0.43 (95% CI -0.85, -0.02, p = 0.04) in those that consumed >1 beverage/month compared to never/seldom consumers. The association was not significant for the consumption of ASB, but point estimates showed negative values, suggesting declines in cognition.
CONCLUSIONS:
Only the consumption of SSB, but not ASB, was significantly associated with a decline in cognitive function after 6 years. Further longitudinal studies are needed to explore the relationship between these beverages and cognitive function and the potential mechanisms through which they might be harmful.
KEYWORDS:
Sugar-sweetened beverages; artificially-sweetened beverages; cognitive function; cognitive screening test; dementia

[AlPater]

Vitamin D Supplements and Total Cancer Incidence and Mortality: a Meta-analysis of randomized controlled trials.
Keum N, Lee DH, Greenwood DC, Manson JE, Giovannucci E.
Ann Oncol. 2019 Feb 22. pii: mdz059. doi: 10.1093/annonc/mdz059. [Epub ahead of print]
PMID: 30796437
Abstract
BACKGROUND:
Previous meta-analyses of randomized controlled trials (RCTs) of vitamin D supplementation and total cancer incidence and mortality found inconsistent results, and most included trials administered generally low doses of vitamin D (≤ 1100 IU/day). We updated the meta-analysis by incorporating recent RCTs that have tested higher doses of vitamin D supplements.
MATERIALS AND METHODS:
PubMed and Embase were searched from the inception to November, 2018. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a random-effects model.
RESULTS:
For total cancer incidence, 10 trials were included (6,547 cases; 3-10 years of follow-up; 54-135 nmol/L of attained levels of circulating 25(OH)vitamin D [25(OH)D] in the intervention group). The summary RR was 0.98 (95% CI, 0.93 to 1.03; P=.42; I2=0%). The results remained null across subgroups tested, including even when attained 25(OH)D levels exceeded 100 nmol/L (RR, 0.95; 95% CI, 0.83 to 1.09; P=.48; I2=26%). For total cancer mortality, 5 trials were included (1,591 deaths; 3-10 years of follow-up; 54-135 nmol/L of attained levels of circulating 25(OH)D in the intervention group). The summary RR was 0.87 (95% CI, 0.79 to 0.96; P=.005; I2=0%), which was largely attributable to interventions with daily dosing (as opposed to infrequent bolus dosing). No statistically significant heterogeneity was observed by attained levels of circulating 25(OH)D (Pheterogeneity=.83), with RR being 0.88 (95% CI, 0.78 to 0.98; P=.02; I2=0%) for ≤ 100 nmol/L and 0.85 (95% CI, 0.70-1.03; P=.11; I2=0%) for > 100 nmol/L.
CONCLUSIONS:
In an updated meta-analysis of RCTs, vitamin D supplementation significantly reduced total cancer mortality but did not reduce total cancer incidence.
KEYWORDS:
Vitamin D supplements; cancer incidence; cancer mortality; circulating 25(OH)D; meta-analysis; randomized controlled trial

An evaluation of the effects of saffron supplementation on the asthma clinical symptoms and asthma severity in patients with mild and moderate persistent allergic asthma: a double-blind, randomized placebo-controlled trial.
Zilaee M, Hosseini SA, Jafarirad S, Abolnezhadian F, Cheraghian B, Namjoyan F, Ghadiri A.
Respir Res. 2019 Feb 22;20(1):39. doi: 10.1186/s12931-019-0998-x.
PMID: 30795753
https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-019-0998-x
Abstract
BACKGROUND:
Asthma is a heterogeneous disease which is usually associated with chronic airway inflammation. Saffron has anti-inflammatory effects and may has beneficial effects on asthma.
HYPOTHESIS:
The present study was intended to survey the effects of saffron supplementation on blood pressure, lipid profiles, basophils, eosinophils and clinical symptoms in patients with allergic asthma.
STUDY DESIGN:
Our study was a clinical trial.
METHODS:
Subjects (N = 80, 32 women and 48 men, 41.25 ± 9.87 years old) with mild and moderate allergic asthma were randomized into two groups: the intervention group who received two capsules of saffron (100 mg/d), and the control group who received two capsules of placebo for 8 weeks. SPSS software (version 16.0) was used for the data analysis.
RESULTS:
Saffron improved the frequency of clinical symptoms of the patients (i.e., frequency of the shortness of breath during the day and night time, use of salbutamol spray, waking up due to asthma symptoms and activity limitation) in comparison to the placebo (p < 0.001). Besides, asthma severity decreased almost significantly in the saffron group (p = 0.07). It was also found that saffron, in comparison with the placebo, significantly reduced the systolic and diastolic blood pressure, triglycerides and low density lipoprotein cholesterol. Moreover, eosinophils and basophils concentration reduced in the saffron group (p = 0.06 and 0.05 respectively).
CONCLUSION:
Saffron seems to be an effective and safe option (in 8 weeks supplementation) to improve clinical symptoms of patients with allergic asthma but the toxicity and/or long-term effects of saffron intake are not known. Registration ID in IRCT (IRCT2017012132081N2).
KEYWORDS:
Allergic asthma; Asthma severity; Saffron

Dose-response associations of cardiorespiratory fitness with all-cause mortality and incidence and mortality of cancer and cardiovascular and respiratory diseases: the UK Biobank cohort study.
Steell L, Ho FK, Sillars A, Petermann-Rocha F, Li H, Lyall DM, Iliodromiti S, Welsh P, Anderson J, MacKay DF, Pell JP, Sattar N, Gill JM, Gray SR, Celis-Morales CA.
Br J Sports Med. 2019 Feb 22. pii: bjsports-2018-099093. doi: 10.1136/bjsports-2018-099093. [Epub ahead of print]
PMID: 30796106
https://sci-hub.tw/10.1136/bjsports-2018-099093
Abstract
OBJECTIVE:
To investigate the association of cardiorespiratory fitness with all-cause mortality, and cardiovascular disease (CVD), respiratory disease, chronic obstructive pulmonary disease (COPD) and cancer mortality and incidence.
DESIGN:
Prospective population-based study.
SETTING:
UK Biobank.
PARTICIPANTS:
Of the 5 02 628 (5.5% response rate) participants recruited by UK Biobank, we included 73 259 (14.6%) participants with available data in this analysis. Of these, 1374 participants died and 4210 developed circulatory diseases, 1293 respiratory diseases and 4281 cancer, over a median of 5.0 years (IQR 4.3-5.7) follow-up.
MAIN OUTCOME MEASURES:
All-cause mortality and circulatory disease, respiratory disease, COPD and cancer (such as colorectal, lung, breast and prostate) mortality/incidence. Fitness was estimated using a submaximal cycle ergometer test.
RESULTS:
The HR for all-cause mortality for each metabolic equivalent of task (MET) higher fitness was 0.96 (95% CI 0.93 to 0.98). Similar results were observed for incident circulatory disease (HR 0.96 [0.95 to 0.97]), respiratory disease (HR 0.96 [0.94 to 0.98]), COPD (HR 0.90 [0.86 to 0.95) and colorectal cancer (HR 0.96 [0.92 to 1.00]). Nonlinear analysis revealed that a high level of fitness (>10METs) was associated with a greater incidence of atrial fibrillation (HR 1.24 [1.07 to 1.44]) and prostate cancer (HR 1.16 [1.02 to 1.32]) compared with average fitness. All results were adjusted for sociodemographic, lifestyle and dietary factors, body composition, and morbidity at baseline and excluded events in the first 2 years of follow-up.
CONCLUSIONS:
Higher cardiorespiratory fitness was associated with lower risk of premature mortality and incidence of CVD, respiratory disease and colorectal cancer.
KEYWORDS:
cancer; cardiovascular; epidemiology; fitness; respiratory

[AlPater]

Lifetime alcohol intake and pancreatic cancer incidence and survival: findings from the Melbourne Collaborative Cohort Study.
Jayasekara H, English DR, Hodge AM, Room R, Hopper JL, Milne RL, Giles GG, MacInnis RJ.
Cancer Causes Control. 2019 Feb 23. doi: 10.1007/s10552-019-01146-6. [Epub ahead of print]
PMID: 30798509
Abstract
PURPOSE:
Pancreatic cancer has one of the worst prognoses with 5-year survival below 10%. There is some evidence that alcohol consumption might increase the risk of pancreatic cancer. We examined associations of pre-diagnostic alcohol intake with (i) incidence of pancreatic cancer, and (ii) overall survival following pancreatic cancer.
METHODS:
Usual alcohol intake was estimated at recruitment in 1990-1994 for 38,472 participants in the Melbourne Collaborative Cohort Study using recalled frequency and quantity of beverage-specific intake for 10-year periods from age 20. Pancreatic cancer incidence (C25 according to International Classification of Diseases for Oncology) and vital status were ascertained through to 30 September 2015. Cox regression was performed to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with lifetime, age 20-29, and baseline alcohol intakes.
RESULTS:
By the end of follow-up (average 20.2 years), 239 incident cases of pancreatic cancer were diagnosed, of which 228 had died. No evidence of an association was observed between alcohol intake and risk of pancreatic cancer. Higher lifetime alcohol intake was associated with lower overall survival following a diagnosis of pancreatic cancer (mortality HR 1.09 per 10 g/day increment, 95% CI 1.00-1.19; p value = 0.04). A similar finding was observed for age 20-29 intake (HR 1.09 per 10 g/day increment, 95% CI 1.02-1.18; p value = 0.01) but not with baseline intake.
CONCLUSIONS:
We observed an association between lower alcohol use from an early age and improved survival following pancreatic cancer, but this finding needs to be confirmed by other studies.
KEYWORDS:
Alcohol intake; Incidence; Pancreatic cancer; Survival

Impact of estrogen monotherapy on survival in women with stage III-IV non-small cell lung cancer.
Heilbroner SP, Xanthopoulos EP, Buono D, Huang Y, Carrier D, Shah A, Kim J, Corradetti M, Wright JD, Neugut AI, Hershman DL, Cheng SK.
Lung Cancer. 2019 Mar;129:8-15. doi: 10.1016/j.lungcan.2018.12.021. Epub 2018 Dec 24.
PMID: 30797496
Abstract
OBJECTIVES:
Women with lung cancer have better survival than men. The reasons are unknown, but estrogen is hypothesized to improve survival. Our objective was to examine the association between estrogen monotherapy and cancer-specific and overall survival in elderly women with non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS:
We used the SEER-Medicare database to identify women ≥65 years old who were diagnosed with stage III or IV NSCLC. Estrogen monotherapy (EM) was defined as at least one estrogen claim without any progesterone claims 6 months prior to diagnosis. To assess cancer-specific survival and overall survival, we used Kaplan-Meier and multivariate Cox modeling with propensity score adjustments. As an exploratory analysis, we also examined the effect of combined estrogen and progesterone hormonal therapy on survival using Cox modeling.
RESULTS:
We identified 6958 women in our initial cohort: 283 used EM (4%) and 6675 (96%) did not. The median follow-up time was 46.5 months in the EM patients and 49.5 months in the non-EM patients. In a Kaplan-Meier analysis, median overall survival was 8.2 months in patients who receive EM and 6.2 months in those who did not (p = 0.004). In our 1:4 propensity-matched cohort, median follow-up was 46.5 in the EM group and 50.6 in the non-EM group; median overall survival was 8.0 months in the EM group and 6.4 months in the non-EM group (p = 0.02). In a multivariate Cox regression of the matched cohort, EM was significantly associated with overall survival (HR 0.84; 95% CI 0.73 - 0.97). All results were similar for cancer-specific survival. In our exploratory analysis, combined Estrogen-Progesterone did significantly impact overall survival (HR 0.84; 95% CI 0.71-0.99, p = 0.04) but did not appear to effect cancer-specific survival (HR 0.91; 95% CI 0.77-1.09, p = 0.30).
CONCLUSION:
EM was associated with a significant improvement in cancer-specific survival and overall survival in women with late stage NSCLC.
KEYWORDS:
Estrogen; Locally advanced; NSCLC; Non-small-cell lung cancer; Outcomes

Incidence of dementia after age 90 in a multiracial cohort.
Gilsanz P, Corrada MM, Kawas CH, Mayeda ER, Glymour MM, Quesenberry CP Jr, Lee C, Whitmer RA.
Alzheimers Dement. 2019 Feb 8. pii: S1552-5260(18)33623-9. doi: 10.1016/j.jalz.2018.12.006. [Epub ahead of print]
PMID: 30797730
Abstract
INTRODUCTION:
Little is known about dementia incidence in diverse populations of oldest-old, the age group with highest dementia incidence.
METHODS:
Incident dementia diagnoses from 1/1/2010 to 9/30/2015 were abstracted from medical records for 2350 members of an integrated health care system in California (n = 1702 whites, n = 375 blacks, n = 105 Latinos, n = 168 Asians) aged ≥90 in 2010. We estimated race/ethnicity-specific age-adjusted dementia incidence rates and implemented Cox proportional hazards models and Fine and Gray competing risk of death models adjusted for demographics and comorbidities in midlife and late-life.
RESULTS:
Dementia incidence rates (n = 771 cases) were lowest among Asians (89.9/1000 person-years), followed by whites (96.9/1000 person-years), Latinos (105.8/1000 person-years), and blacks (121.5/1000 person-years). Cox regression and competing risk models estimated 28% and 36% higher dementia risk for blacks versus whites adjusting for demographics and comorbidities.
DISCUSSION:
Patterns of racial/ethnic disparities in dementia seen in younger older adults continue after the age of 90 years, though smaller in magnitude.
KEYWORDS:
Dementia; Disparities; Epidemiology; Ethnicity; Oldest-old; Race

Declining cancer incidence at the oldest ages: Hallmark of aging or lower diagnostic activity?
Pedersen JK, Rosholm JU, Ewertz M, Engholm G, Lindahl-Jacobsen R, Christensen K.
J Geriatr Oncol. 2019 Feb 20. pii: S1879-4068(18)30346-1. doi: 10.1016/j.jgo.2019.02.001. [Epub ahead of print]
PMID: 30797708
Abstract
BACKGROUND:
The incidence of most cancers increases with age from early adulthood into old age but tends to level off or decrease at the highest ages. This decline may be caused by age-related mechanisms or due to lower diagnostic activity, leaving some cancers undiagnosed at the oldest ages.
METHODS:
For breast, colon, lung, and all sites except non-melanoma skin cancer, age-specific incidence rates of verified as well as suspected cancer were estimated up to ages 95+ years for a random sample of the Danish population, 1994-2011, based on nationwide health registers (40,008 verified and 9110 suspected cancers). Moreover, for cancers diagnosed in Denmark, 1978-2012 (613,384 cancers), age-specific percentages of tumors with microscopic verification (histological/cytological/hematological examination) were calculated.
RESULTS:
The age-specific cancer incidence rates reached a peak between ages 65-89 years after which rates declined. The corresponding incidence pattern of suspected but not verified cancer was similar, with a trend of a slight absolute and relative decrease with age compared to verified cancer incidence. The proportion of cancers with microscopic verification decreased linearly from approximately 95% at ages 0-69 years all years to 70% (1978-1982) and to 80% (2010-2012) at ages 90+ years.
CONCLUSIONS:
The lower diagnostic verification of cancer at the highest ages suggests a lower diagnostic activity among the oldest-old. However, the proportion of suspected but not verified cancers did not increase with age, possibly partially due to lack of registration. The declining cancer incidence at oldest ages is probably partly due to lower diagnostic activity.
KEYWORDS:
Aged; Aged, 80 and over; Bias; Epidemiology; Incidence; Neoplasms

[AlPater]

Intake of Individual Fatty Acids and Risk of Prostate Cancer in the European Prospective Investigation into Cancer and Nutrition.
Perez-Cornago A, Huybrechts I, Appleby PN, Schmidt JA, Crowe FL, Overvad K, Tjønneland A, Kühn T, Katzke V, Trichopoulou A, Karakatsani A, Peppa E, Grioni S, Palli D, Sacerdote C, Tumino R, Bueno-de-Mesquita HB, Larrañaga N, Sánchez MJ, Quirós JR, Ardanaz E, Chirlaque MD, Agudo A, Bjartell A, Wallström P, Chajes V, Tsilidis KK, Aune D, Riboli E, Travis RC, Key TJ.
Int J Cancer. 2019 Feb 26. doi: 10.1002/ijc.32233. [Epub ahead of print]
PMID: 30807653
Abstract
The associations of individual dietary fatty acids with prostate cancer risk have not been examined comprehensively. We examined the prospective association of individual dietary fatty acids with prostate cancer risk overall, by tumor subtypes, and prostate cancer death. 142,239 men from the European Prospective Investigation into Cancer and Nutrition who were free from cancer at recruitment were included. Dietary intakes of individual fatty acids were estimated using center-specific validated dietary questionnaires at baseline and calibrated with 24-hour recalls. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average follow-up of 13.9 years, 7,036 prostate cancer cases and 936 prostate cancer deaths were ascertained. Intakes of individual fatty acids were not related to overall prostate cancer risk. There was evidence of heterogeneity in the association of some short chain saturated fatty acids with prostate cancer risk by tumor stage (Pheterogeneity <0.015), with a positive association with risk of advanced stage disease for butyric acid (4:0; HR1SD =1.08; 95%CI=1.01-1.15; P-trend=0.026). There were no associations with fatal prostate cancer, with the exception of a slightly higher risk for those who consumed more eicosenoic acid (22:1n-9c; HR1SD =1.05; 1.00-1.11; P-trend=0.048) and eicosapentaenoic acid (20:5n-3c; HR1SD =1.07; 1.00-1.14; P-trend=0.045). There was no evidence that dietary intakes of individual fatty acids were associated with overall prostate cancer risk. However, a higher intake of butyric acid might be associated with a higher risk of advanced, whereas intakes of eicosenoic and eicosapentaenoic acids might be positively associated with fatal prostate cancer risk.
KEYWORDS:
individual fatty acids; prospective; prostate cancer; tumor subtypes

Fish consumption and risk of myocardial infarction: a systematic review and dose-response meta-analysis suggests a regional difference.
Jayedi A, Zargar MS, Shab-Bidar S.
Nutr Res. 2019 Feb;62:1-12. doi: 10.1016/j.nutres.2018.10.009. Epub 2018 Nov 4. Review.
PMID: 30803501
Abstract
Limited evidence suggests that the association between fish consumption and risk of cardiovascular disease may be confounded by some regional-related factors. We aimed to quantify the association of fish consumption with risk of myocardial infarction (MI) and to clarify the shape of the dose-response relation in Western and Asian countries. A systematic literature review was performed in PubMed and Scopus from inception to January 2018. Prospective observational studies reporting risk estimates of MI for 3 or more quantitative categories of fish intake were included. A random-effects dose-response meta-analysis was conducted. Eleven prospective cohort studies, comprising a total of 398,221 participants and 8468 cases of MI, were analyzed. A significant inverse association was found for the highest compared with the lowest category of fish intake (relative risk: 0.73, 95% confidence interval: 0.59-0.87; I2 = 72%) and for a 15-g/d (105 g/wk, approximately equal to a 1 serving/wk) increment in fish consumption (relative risk: 0.96, 95% confidence interval: 0.94-0.99; I2 = 65%). A subgroup analysis showed a significant inverse association only in the subgroup of Asian studies as compared to Western studies. A nonlinear dose-response analysis suggested a linear decrement in the risk with the increase in fish consumption in the analysis of Asian studies. A modest U-shaped association was observed in the analysis of Western studies. In conclusion, higher fish consumption was associated with a lower risk of MI. However, considering the observed regional difference in this association, further observational studies are needed to provide more detailed explanations about this difference.
KEYWORDS:
Cardiovascular disease; Fish; Meta-analysis; Myocardial infarction; Regional difference

The preventable burden of breast cancers for premenopausal and postmenopausal women in Australia: a pooled cohort study.
Arriaga ME, Vajdic CM, Canfell K, MacInnis RJ, Banks E, Byles JE, Magliano DJ, Taylor AW, Mitchell P, Giles GG, Shaw JE, Gill TK, Klaes E, Velentzis LS, Cumming RG, Hirani V, Laaksonen MA.
Int J Cancer. 2019 Feb 25. doi: 10.1002/ijc.32231. [Epub ahead of print]
PMID: 30802946
Abstract
Estimates of the future breast cancer burden preventable through modifications to current behaviours are lacking. We assessed the effect of individual and joint behaviour modifications on breast cancer burden for premenopausal and postmenopausal Australian women, and whether effects differed between population subgroups. We linked pooled data from six Australian cohort studies (N=214,536) to national cancer and death registries, and estimated the strength of the associations between behaviours causally related to cancer incidence and death using adjusted proportional hazards models. We estimated exposure prevalence from representative health surveys. We combined these estimates to calculate Population Attributable Fractions (PAFs) with 95% confidence intervals (CIs), and compared PAFs for population subgroups. During the first 10-years follow-up, there were 640 incident breast cancers for premenopausal women, 2,632 for postmenopausal women, and 8,761 deaths from any cause. Of future breast cancers for premenopausal women, any regular alcohol consumption explains 12.6% (CI=4.3-20.2%), current use of oral contraceptives for ≥5 years 7.1% (CI=0.3-13.5%), and these factors combined 18.8% (CI=9.1-27.4%). Of future breast cancers for postmenopausal women, overweight or obesity (BMI ≥25 kg/m2 ) explains 12.8% (CI=7.8-17.5%), current use of menopausal hormone therapy (MHT) 6.9% (CI=4.8-8.9%), any regular alcohol consumption 6.6% (CI=1.5-11.4%), and these factors combined 24.2% (CI=17.6-30.3%). The MHT-related postmenopausal breast cancer burden varied by body fatness, alcohol consumption and socio-economic status, the body fatness-related postmenopausal breast cancer burden by alcohol consumption and educational attainment, and the alcohol-related postmenopausal breast cancer burden by breast feeding history. Our results provide evidence to support targeted and population-level cancer control activities.
KEYWORDS:
breast cancer; cohort; population attributable fraction; preventable; risk factors

Cinnamon supplementation positively affects obesity: A systematic review and dose-response meta-analysis of randomized controlled trials.
Mousavi SM, Rahmani J, Kord-Varkaneh H, Sheikhi A, Larijani B, Esmaillzadeh A.
Clin Nutr. 2019 Feb 15. pii: S0261-5614(19)30071-8. doi: 10.1016/j.clnu.2019.02.017. [Epub ahead of print]
PMID: 30799194
Abstract
BACKGROUND & AIMS:
Data about the effects of cinnamon supplementation on obesity measures are conflicting. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the effects of cinnamon intake on body weight (BW), Body Mass Index (BMI), Waist Circumference (WC), and fat mass (FM) in adults.
METHODS:
Online electronic search engines including PubMed, SCOPUS, Cochrane Library, and Google Scholar were searched to find pertinent articles until September 2018. Data were pooled using the random-effects method and were expressed as weighted mean difference (WMD) and 95% confidence intervals (CI). The non-linear association was assessed using fractional polynomial modeling.
RESULTS:
Out of 679 records, 12 trials that enrolled 786 subjects were included. The pooled results showed that cinnamon administration significantly decreased BW (WMD: -1.02 kg, 95% CI: -1.66 to -0.38, P = 0.002), BMI (WMD: -0.51 kg/m2, 95% CI: -0.74, -0.28, P < 0.001), WC (WMD: -2.40 cm, 95% CI: -4.48, -0.33, P = 0.02), and FM (WMD: -1.02%, 95% CI: -1.80, -0.24, P = 0.01). Greater effects on BW were observed in subjects aged <50 years old and those with a baseline BMI of ≥30 kg/m2. The cinnamon administrations significantly reduced FM at the dosages of ≥2 g/d, when administered for ≥12 weeks. Cinnamon administration resulted in BW and WC reduction in non-linear fashion (P = 0.04).
CONCLUSIONS:
Cinnamon supplementation significantly affects obesity measures. It could be recommended as a weight-reducing supplement in obesity management.
KEYWORDS:
Cinnamon; Dose-response; Meta-analysis; Obesity; Weight

Chocolate and risk of chronic disease: a systematic review and dose-response meta-analysis.
Morze J, Schwedhelm C, Bencic A, Hoffmann G, Boeing H, Przybylowicz K, Schwingshackl L.
Eur J Nutr. 2019 Feb 25. doi: 10.1007/s00394-019-01914-9. [Epub ahead of print]
PMID: 30805697
Abstract
PURPOSE:
Evidence for the association between chocolate intake and risk of chronic diseases is inconclusive. Therefore, we aimed to synthesize and evaluate the credibility of evidence on the dose-response association between chocolate consumption with risk of all-cause mortality, coronary heart disease (CHD), stroke, heart failure (HF), type 2 diabetes (T2D), colorectal cancer (CRC), and hypertension.
METHODS:
Prospective studies were searched until July 2018 in PubMed, Embase, and Web of Science. Random-effects meta-analyses comparing highest versus lowest intake categories, linear, and non-linear dose-response analyses were conducted. The credibility of evidence was evaluated with the NutriGrade scoring-system.
RESULTS:
Overall, 27 investigations were identified (n = 2 for all-cause mortality, n = 9 for CHD, n = 8 for stroke, n = 6 for HF, n = 6 for T2D, n = 2 for hypertension and CRC, respectively). No associations with HF (RR 0.99, 95% CI 0.94, 1.04) and T2D (RR 0.94, 95% CI 0.88, 1.01) per each 10 g/day increase in chocolate intake were observed in the linear dose-response meta-analyses. However, a small inverse association for each 10 g/daily increase could be shown for the risk of CHD (RR 0.96, 95% CI 0.93, 0.99), and stroke (RR 0.90, 95% CI 0.82, 0.98). The credibility of evidence was rated either very low (all-cause mortality, HF, T2D, CRC or hypertension) or low (CHD, stroke).
CONCLUSION:
Chocolate consumption is not related to risk for several chronic diseases, but could have a small inverse association with CHD and stroke. Our findings are limited by very low or low credibility of evidence, highlighting important uncertainty for chocolate-disease associations.
KEYWORDS:
Chocolate; Chronic disease; Credibility of evidence; Dose-response; Meta-analysis

A high methionine, low folate and vitamin B6/B12 containing diet can be associated with memory loss by epigenetic silencing of netrin-1.
Kalani A, Chaturvedi P, Kalani K, Kamat PK, Chaturvedi P, Tyagi N.
Neural Regen Res. 2019 Jul;14(7):1247-1254. doi: 10.4103/1673-5374.251333.
PMID: 30804256
http://www.nrronline.org/temp/NeuralRegenRes1471247-3789454_103134.pdf
Abstract
Memory-epigenetics which is the loss of memory due to epigenetic modifications can be due to the silencing of genes involved in cognitive functions and this is the basis of the current study. We hypothesize that a diet containing high methionine and low vitamins can lead to memory impairment by increasing global DNA methylation and therefore, silencing the netrin-1 gene, which encodes the glycoprotein involved in neurogenesis, axonal guidance and maintenance of the synaptic plasticity. Wild type (C57BL/6J) mice were fed with a diet containing excess methionine (1.2%), low-folate (0.08 mg/kg), vitamin B6 (0.01 mg/kg), and B12 (10.4 mg/kg) for 6 weeks. Mice were examined weekly for the long-term memory function, using a passive avoidance test, which determined loss of fear-motivated long-term memory starting from the fourth week of diet. Similarly, an increase in brain %5-methyl cytosine was observed starting from the 4th week of diet in mice. Mice fed with a high methionine, low folate and vitamins containing diet showed a decrease in netrin-1 protein expression and an increase in netrin-1 gene promotor methylation, as determined by methylation-sensitive restriction enzyme-polymerase chain reaction analysis. The increase in methylation of netrin-1 gene was validated by high-resolution melting and sequencing analysis. Furthermore, the association of netrin-1 with memory was established by administering netrin that considerably restored long-term fear motivated memory. Taken together, these results suggest that a diet rich in methionine and lacking in folate and vitamin B6/B12 can induce defects in learning and memory. Furthermore, the data indicates that decrease in netrin-1 expression due to hyper-methylation of its gene can be associated with memory loss. 
KEYWORDS:
5-methylcytosine; Alzheimer's disease; epigenetics; memory; methionine; methylation; netrin-1

Activation of vitamin D in the gingival epithelium and its role in gingival inflammation and alveolar bone loss.
Menzel LP, Ruddick W, Chowdhury MH, Brice DC, Clance R, Porcelli E, Ryan LK, Lee J, Yilmaz Ö, Kirkwood KL, McMahon L, Tran A, Diamond G.
J Periodontal Res. 2019 Feb 25. doi: 10.1111/jre.12646. [Epub ahead of print]
PMID: 30802957
Abstract
BACKGROUND AND OBJECTIVE:
Both chronic and aggressive periodontal disease are associated with vitamin D deficiency. The active form of vitamin D, 1,25(OH)2 D3 , induces the expression of the antimicrobial peptide LL-37 and innate immune mediators in cultured human gingival epithelial cells (GECs). The aim of this study was to further delineate the mechanism by which vitamin D enhances the innate defense against the development of periodontal disease (PD).
MATERIALS AND METHODS:
Wild-type C57Bl/6 mice were made deficient in vitamin D by dietary restriction. Cultured primary and immortalized GEC were stimulated with 1,25(OH)2 D3 , followed by infection with Porphyromonas gingivalis, and viable intracellular bacteria were quantified. Conversion of vitamin D3 to 25(OH)D3 and 1,25(OH)2 D3 was quantified by ELISA. Effect of vitamin D on basal IL-1α expression in mice was determined by topical administration to the gingiva of wild-type mice, followed by qRT-PCR.
RESULTS:
Dietary restriction of vitamin D led to alveolar bone loss and increased inflammation in the gingiva in the mouse model. In primary human GEC and established human cell lines, treatment of GEC with 1,25(OH)2 D3 inhibited the intracellular growth of P. gingivalis. Cultured GEC expressed two 25-hydroxylases (CYP27A1 and CYP2R1), as well as 1-α hydroxylase, enabling conversion of vitamin D to both 25(OH)D3 and 1,25(OH)2 D3 . Topical application of both vitamin D3 and 1,25(OH)2 D3 to the gingiva of mice led to rapid inhibition of IL-1α expression, a prominent pro-inflammatory cytokine associated with inflammation, which also exhibited more than a 2-fold decrease from basal levels in OKF6/TERT1 cells upon 1,25(OH)2 D3 treatment, as determined by RNA-seq.
CONCLUSION:
Vitamin D deficiency in mice contributes to PD, recapitulating the association seen in humans, and provides a unique model to study the development of PD. Vitamin D increases the activity of GEC against the invasion of periodontal pathogens and inhibits the inflammatory response, both in vitro and in vivo. GEC can convert inactive vitamin D to the active form in situ, supporting the hypothesis that vitamin D can be applied directly to the gingiva to prevent or treat periodontal disease.
KEYWORDS:
antimicrobial peptide; inflammation; periodontal disease; vitamin D

Colonoscopy in Nonagenarians Is Safe and May Be Associated with Clinical Benefit.
Shafrir A, Koslowsky B, Wengrower D, Goldin E, Livovsky DM.
J Am Geriatr Soc. 2019 Feb 22. doi: 10.1111/jgs.15832. [Epub ahead of print]
PMID: 30801669
Abstract
OBJECTIVES:
Data regarding colonoscopy in patients older than 90 years old is scarce. Yet the number of colonoscopies done on nonagenarians is rising. We aimed to determine the yield, safety, and therapeutic benefits of colonoscopy in these patients.
DESIGN:
Case-control study of older patients who underwent colonoscopy.
SETTING:
Gastroenterology institute at an academic medical center.
PARTICIPANTS:
Patients older than 90 years (n = 128) compared with patients aged 80 to 89 years (n = 218) who underwent colonoscopy.
INTERVENTION:
Colonoscopy.
MEASUREMENTS:
Indication for the procedure, completion rates, adequacy of preparation, complications, colonoscopic findings, 30-day mortality, advanced adenoma and carcinoma detection rate, treatment, and long-term survival of patients diagnosed with colorectal cancer.
RESULTS:
Mean ages were 83.3 and 92.2 years old. Nonagenarians were more likely to undergo a colonoscopy while hospitalized (56.2 vs 23.4%; P < .001) and to undergo the examination due to rectal bleeding or sigmoid volvulus (35.2 vs 25.2 and 10.9 vs 0.5%, respectively; P < .001) and less likely for surveillance or constipation (11.7 vs 25.7 and 0 vs 6.9%, respectively; P < .001). Completion rates and severe adverse events were comparable. The 30-day mortality was 3.9% in nonagenarians and 0.4% in octogenarians (P = .02). Advanced adenomas and carcinoma were more common in nonagenarians (25.8 vs 16.5%, P = .03, and 14.8 vs 6.4%, P = .01, respectively). Increasing age, inpatient status, past polypectomy surveillance, and anemia were associated with higher rates of carcinoma. Half of the nonagenarians diagnosed with adenocarcinoma underwent surgery compared with 100% of octogenarians (P = .01). Among nonagenarians with colorectal cancer who died, mean survival was 605 (interquartile range = 11-878) days in those who underwent surgery and 112 (48-341) in those treated conservatively (P = .055 log-rank test).
CONCLUSION:
Colonoscopy in nonagenarians has a high yield and is generally safe. Colonoscopy findings lead to surgery in more than half of these patients and was associated with a median survival of 20 months.

Artificially Sweetened Beverages and Stroke, Coronary Heart Disease, and All-Cause Mortality in the Women's Health Initiative.
Mossavar-Rahmani Y, Kamensky V, Manson JE, Silver B, Rapp SR, Haring B, Beresford SAA, Snetselaar L, Wassertheil-Smoller S.
Stroke. 2019 Mar;50(3):555-562. doi: 10.1161/STROKEAHA.118.023100.
PMID: 30802187
Abstract
Background and Purpose- We examine the association between self-reported consumption of artificially sweetened beverages (ASB) and stroke and its subtypes, coronary heart disease, and all-cause mortality in a cohort of postmenopausal US women. Methods- The analytic cohort included 81 714 women from the Women's Health Initiative Observational Study, a multicenter longitudinal study of the health of 93 676 postmenopausal women of ages 50 to 79 years at baseline who enrolled in 1993 to 1998. This prospective study had a mean follow-up time of 11.9 years (SD of 5.3 years.) Participants who completed a follow-up visit 3 years after baseline were included in the study. Results- Most participants (64.1%) were infrequent consumers (never or <1/week) of ASB, with only 5.1% consuming ≥2 ASBs/day. In multivariate analyses, those consuming the highest level of ASB compared to never or rarely (<1/wk) had significantly greater likelihood of all end points (except hemorrhagic stroke), after controlling for multiple covariates. Adjusted models indicated that hazard ratios and 95% confidence intervals were 1.23 (1.02-1.47) for all stroke; 1.31 (1.06-1.63) for ischemic stroke; 1.29 (1.11-1.51) for coronary heart disease; and 1.16 (1.07-1.26) for all-cause mortality. In women with no prior history of cardiovascular disease or diabetes mellitus, high consumption of ASB was associated with more than a 2-fold increased risk of small artery occlusion ischemic stroke hazard ratio =2.44 (95% confidence interval, 1.47-4.04.) High consumption of ASBs was associated with significantly increased risk of ischemic stroke in women with body mass index ≥30; hazard ratio =2.03 (95% confidence interval, 1.38-2.98). Conclusions- Higher intake of ASB was associated with increased risk of stroke, particularly small artery occlusion subtype, coronary heart disease, and all-cause mortality. Although requiring replication, these new findings add to the potentially harmful association of consuming high quantities of ASB with these health outcomes.
KEYWORDS:
brain ischemia; coronary heart disease; diabetes mellitus; stroke; sweetening agents

[AlPater]

MEDIA ADVISORY: 
Longevity and Age Reversal 
presented by Brian M. Delaney and William Faloon
https://menafn.com/1098184037/MEDIA-ADVISORY-Longevity-and-Age-Reversal-presented-by-Brian-M-Delaney-and-William-Faloon

Dietary fibers as emerging nutritional factors against diabetes: focus on the involvement of gut microbiota.
Gowd V, Xie L, Zheng X, Chen W.
Crit Rev Biotechnol. 2019 Feb 27:1-17. doi: 10.1080/07388551.2019.1576025. [Epub ahead of print]
PMID: 30810398
https://sci-hub.tw/10.1080/07388551.2019.1576025
Abstract
Diabetes mellitus (DM) increases the risk of cardiovascular diseases and other secondary complications, such as nephropathy, neuropathy, retinopathy, etc. The important risk factors for the pathogenesis of DM are aging, family history, sedentary lifestyle, unhealthy dietary habits, and obesity. Evidence from epidemiological studies also indicates that DM is characterized by specific alterations in the human gut microbiota (GM). GM transplantation in rodents and humans revealed that a specific GM constituent can be the cause and not just the consequence of the DM condition and complications. These findings suggest a potential role of GM in human health, disease prevention, and treatment. Dietary intervention studies using dietary fibers (DFs) suggested that modulation of the GM can suppress the metabolic risk markers in humans. However, a causal role of GM in such studies remains unexplored. Long-term follow-up studies disclosed that the diet rich in insoluble and non-viscous fibers are responsible for DF-mediated antidiabetic activities, while soluble and viscous fibers have little influence on DM despite having a profound impact on glycemia. However, general conclusions cannot be drawn simply based on these findings. Long-term follow-up studies are urgently required in this area to explore the therapeutic potential of different DFs in treating DM and to delineate the exact role of GM involvement. Here we review and discuss the signature of GM during DM, antidiabetic activity of metformin via GM modulation, DFs from different sources and their antidiabetic activity, and the possible role of GM involvement.
KEYWORDS:
Diabetes mellitus; GLP-1; dietary fibers; glycemic index; gut microbiota; insulin sensitivity; short-chain fatty acids

Association of Maternal Prenatal Vitamin Use With Risk for Autism Spectrum Disorder Recurrence in Young Siblings.
Schmidt RJ, Iosif AM, Guerrero Angel E, Ozonoff S.
JAMA Psychiatry. 2019 Feb 27. doi: 10.1001/jamapsychiatry.2018.3901. [Epub ahead of print]
PMID: 30810722
Abstract
IMPORTANCE:
Maternal use of folic acid supplements has been inconsistently associated with reduced risk for autism spectrum disorder (ASD) in the child. No study to date has examined this association in the context of ASD recurrence in high-risk families.
OBJECTIVE:
To examine the association between maternal prenatal vitamin use and ASD recurrence risk in younger siblings of children with ASD.
DESIGN, SETTING, AND PARTICIPANTS:
This prospective cohort study analyzed data from a sample of children (n = 332) and their mothers (n = 305) enrolled in the MARBLES (Markers of Autism Risk in Babies: Learning Early Signs) study. Participants in the MARBLES study were recruited at the MIND Institute of the University of California, Davis and were primarily from families receiving services for children with ASD in the California Department of Developmental Services. In this sample, the younger siblings at high risk for ASD were born between December 1, 2006, and June 30, 2015, and completed a final clinical assessment within 6 months of their third birthday. Prenatal vitamin use during pregnancy was reported by mothers during telephone interviews. Data analysis for this study was conducted from January 1, 2017, to December 3, 2018.
MAIN OUTCOMES AND MEASURES:
Autism spectrum disorder, other nontypical development (non-TD), and typical development (TD) were algorithmically defined according to Autism Diagnostic Observation Schedule and Mullen Scales of Early Learning subscale scores.
RESULTS:
After exclusions, the final sample comprised 241 younger siblings, of which 140 (58.1%) were male and 101 (41.9%) were female, with a mean (SD) age of 36.5 (1.6) months. Most mothers (231 [95.9%]) reported taking prenatal vitamins during pregnancy, but only 87 mothers (36.1%) met the recommendations to take prenatal vitamins in the 6 months before pregnancy. The prevalence of ASD was 14.1% (18) in children whose mothers took prenatal vitamins in the first month of pregnancy compared with 32.7% (37) in children whose mothers did not take prenatal vitamins during that time. Children whose mothers reported taking prenatal vitamins during the first month of pregnancy were less likely to receive an ASD diagnosis (adjusted relative risk [RR], 0.50; 95% CI, 0.30-0.81) but not a non-TD 36-month outcome (adjusted RR, 1.14; 95% CI, 0.75-1.75) compared with children whose mothers reported not taking prenatal vitamins. Children in the former maternal prenatal vitamin group also had statistically significantly lower autism symptom severity (adjusted estimated difference, -0.60; 95% CI, -0.97 to -0.23) and higher cognitive scores (adjusted estimated difference, 7.1; 95% CI, 1.2-13.1).
CONCLUSIONS AND RELEVANCE:
Maternal prenatal vitamin intake during the first month of pregnancy may reduce ASD recurrence in siblings of children with ASD in high-risk families. Additional research is needed to confirm these results; to investigate dose thresholds, contributing nutrients, and biologic mechanisms of prenatal vitamins; and to inform public health recommendations for ASD prevention in affected families.

[AlPater]

The effects of dietary methionine restriction on the function and metabolic reprogramming in the liver and brain - implications for longevity.
Mladenović D, Radosavljević T, Hrnčić D, Rasic-Markovic A, Stanojlović O.
Rev Neurosci. 2019 Feb 28. pii: /j/revneuro.ahead-of-print/revneuro-2018-0073/revneuro-2018-0073.xml. doi: 10.1515/revneuro-2018-0073. [Epub ahead of print]
PMID: 30817309
Abstract
Methionine is an essential sulphur-containing amino acid involved in protein synthesis, regulation of protein function and methylation reactions. Dietary methionine restriction (0.12-0.17% methionine in food) extends the life span of various animal species and delays the onset of aging-associated diseases and cancers. In the liver, methionine restriction attenuates steatosis and delays the development of non-alcoholic steatohepatitis due to antioxidative action and metabolic reprogramming. The limited intake of methionine stimulates the fatty acid oxidation in the liver and the export of lipoproteins as well as inhibits de novo lipogenesis. These effects are mediated by various signaling pathways and effector molecules, including sirtuins, growth hormone/insulin-like growth factor-1 axis, sterol regulatory element binding proteins, adenosine monophosphate-dependent kinase and general control nonderepressible 2 pathway. Additionally, methionine restriction stimulates the synthesis of fibroblast growth factor-21 in the liver, which increases the insulin sensitivity of peripheral tissues. In the brain, methionine restriction delays the onset of neurodegenerative diseases and increases the resistance to various forms of stress through antioxidative effects and alterations in lipid composition. This review aimed to summarize the morphological, functional and molecular changes in the liver and brain caused by the methionine restriction, with possible implications in the prolongation of maximal life span.
KEYWORDS:
brain; liver; longevity; metabolic changes; methionine restriction; oxidative stress

Fasting reduces oxidative stress, mitochondrial dysfunction and fibrosis induced by renal ischemia-reperfusion injury.
Rojas-Morales P, León-Contreras JC, Aparicio-Trejo OE, Reyes-Ocampo JG, Medina-Campos ON, Jiménez-Osorio AS, González-Reyes S, Marquina-Castillo B, Hernández-Pando R, Barrera-Oviedo D, Sánchez-Lozada LG, Pedraza-Chaverri J, Tapia E.
Free Radic Biol Med. 2019 Feb 25. pii: S0891-5849(18)32438-9. doi: 10.1016/j.freeradbiomed.2019.02.018. [Epub ahead of print]
PMID: 30818054
Abstract
Food deprivation protects against ischemia-reperfusion (IR) injury through unknown mechanisms. In an experimental rat model of acute IR injury, we found that preoperative fasting for 3 days protects rats from tubular damage and renal functional decline by increasing antioxidant protection independently of the NF-E2-related factor 2 (Nrf2), and by maintaining mitochondrial morphology and function. In addition, further analysis revealed that fasting protects against tubulointerstitial fibrosis. In summary, our results point out to fasting as a robust nutritional intervention to limit oxidative stress and mitochondrial dysfunction in early acute kidney injury and also to promote long-term protection against fibrosis.
KEYWORDS:
Acute kidney injury; Chronic kidney disease; Fasting; Fibrosis; Ischemia-reperfusion injury; Mitochondrial dysfunction; Oxidative stress

Refined versus Extra Virgin Olive Oil High-Fat Diet Impact on Intestinal Microbiota of Mice and Its Relation to Different Physiological Variables.
Martínez N, Prieto I, Hidalgo M, Segarra AB, Martínez-Rodríguez AM, Cobo A, Ramírez M, Gálvez A, Martínez-Cañamero M.
Microorganisms. 2019 Feb 23;7(2). pii: E61. doi: 10.3390/microorganisms7020061.
PMID: 30813410
https://www.mdpi.com/2076-2607/7/2/61/htm
Abstract
Extra virgin olive oil (EVOO) has been reported to have a distinct influence on gut microbiota in comparison to other fats, with its physiological benefits widely studied. However, a large proportion of the population consumes olive oil after a depurative process that not only mellows its taste, but also deprives it of polyphenols and other minority components. In this study, we compare the influence on the intestinal microbiota of a diet high in this refined olive oil (ROO) with other fat-enriched diets. Swiss Webster mice were fed standard or a high-fat diet enriched with EVOO, ROO, or butter (BT). Physiological parameters were also evaluated. At the end of the feeding period, DNA was extracted from feces and the 16S rRNA was pyrosequenced. The group fed ROO behaved differently to the EVOO group in half the families with statistically significant differences among the diets, with higher comparative levels in three families-Desulfovibrionaceae, Spiroplasmataceae, and Helicobacteraceae-correlating with total cholesterol. These results are again indicative of a link between specific diets, certain physiological parameters and the prevalence of some taxa, but also support the possibility that polyphenols and minor components of EVOO are involved in some of the proposed effects of this fat through the modulation of the intestinal microbiota.
KEYWORDS:
butter; gut microbiota; next generation sequencing; olive oil; polyphenols

[AlPater]

Alcohol consumption and incident diabetes: The Atherosclerosis Risk in Communities (ARIC) study.
He X, Rebholz CM, Daya N, Lazo M, Selvin E.
Diabetologia. 2019 Feb 28. doi: 10.1007/s00125-019-4833-1. [Epub ahead of print]
PMID: 30820594
Abstract
AIMS/HYPOTHESIS:
The aim of this study was to evaluate the prospective association between baseline and 9 year change in alcohol consumption and long-term risk of diabetes and whether these associations might be modified by sex and/or BMI.
METHODS:
We conducted a prospective analysis of 12,042 Atherosclerosis Risk in Communities (ARIC) study participants without prevalent diabetes (55% women, 78% white, mean age 54 years). Alcohol consumption was assessed at visit 1 (1987-1989) and visit 4 (1996-1998). We used Cox models to estimate hazard ratios for diabetes risk by baseline drinking categories and change in alcohol consumption, stratified by sex and obesity status.
RESULTS:
During a median follow-up of 21 years, there were 3795 incident cases of diabetes. Among women, consuming 8-14 drinks/week was associated with a significantly lower risk of diabetes (HR 0.75, 95% CI 0.58, 0.96) compared with current drinkers consuming ≤1 drink/week. Among men, consuming 8-14 drinks/week was associated with a borderline significant lower risk of diabetes (HR 0.84, 95% CI 0.70, 1.00) and consuming >14 drinks/week was associated with a significantly lower risk of diabetes (HR 0.81, 95% CI 0.67, 0.97) (pinteraction < 0.01 for sex). For both sexes, among current drinkers, there was a significant decreasing trend in diabetes risk as the alcohol consumption increased. The association was modified by BMI (pinteraction = 0.042 for women, pinteraction < 0.001 for men). In women, the inverse association was only seen among overweight and obese participants. In men, the inverse association was more pronounced among obese participants. On average, drinking status did not change substantially over the 9 year period. For men with alcohol intake ≥7 drinks/week at baseline, decreasing alcohol intake was associated with higher risk of diabetes (HR per daily drink decrease 1.12, 95% CI 1.02, 1.23).
CONCLUSIONS/INTERPRETATION:
In this community-based population, there was an inverse association between alcohol consumption and diabetes risk. The amount of the alcohol consumption associated with lower risk was different in women and men, and the association was more pronounced among participants with higher BMI.
KEYWORDS:
Alcohol; Diabetes

[AlPater]

Reductions in whole-body fat mass but not increases in lean mass predict changes in cardiometabolic health indices with exercise training among weight-stable adults.
Amankwaah AF, Hudson JL, Kim JE, Campbell WW.
Nutr Res. 2018 Nov 11;63:63-69. doi: 10.1016/j.nutres.2018.11.004. [Epub ahead of print]
PMID: 30824398
https://sci-hub.tw/10.1016/j.nutres.2018.11.004
Abstract
We assessed whether body composition changes with 9 months of exercise training predicted changes in cardiometabolic health indices in weight-stable adults. We hypothesized that within ±5% weight change, changes in whole-body fat and lean masses would predict changes in cardiometabolic health indices with exercise training. Using a randomized parallel design, 152 adults (age: 49 ± 8 year; body mass index: 30.0 ± 2.7 kg/m2; mean ± SD) performed resistance exercises 2 d/wk and aerobic exercises 1 d/wk for 9 months. Participants consumed isoenergetic supplements with 0, 10, 20, or 30 g whey protein twice daily and remained weight stable within ±5% of baseline weight. Body weight and composition were measured using dual-energy x-ray absorptiometry pre- and postintervention. Multiple linear regression model was applied for data analyses. Independent of whey protein supplementation, reductions in fat mass predicted increases in high-density lipoprotein cholesterol (unstandardized beta-coefficient [β], -0.03; 95% confidence interval [CI], -0.06 to -0.01; P = .007) and insulin sensitivity index (β, -0.52; 95% CI, -0.95 to -0.09; P = .018) and decreases in waist circumference (β, 0.67; 95% CI, 0.17-1.18; P = .009). In contrast, increases in lean mass did not predict changes in any of the measured cardiometabolic health indices. Health improvements with training that emphasize resistance exercises are typically attributed to increases in lean mass; however, these results underscore reducing body fat to predict cardiometabolic health improvements.
KEYWORDS:
Body composition; Body mass index; Body weight; Exercise; Insulin resistance; Linear models; Waist circumference

[AlPater]

MIND not Mediterranean diet related to 12-year incidence of cognitive impairment in an Australian longitudinal cohort study.
Hosking DE, Eramudugolla R, Cherbuin N, Anstey KJ.
Alzheimers Dement. 2019 Feb 27. pii: S1552-5260(18)33628-8. doi: 10.1016/j.jalz.2018.12.011. [Epub ahead of print] Review.
PMID: 30826160
https://sci-hub.tw/10.1016/j.jalz.2018.12.011
Abstract
INTRODUCTION:
Associations between the Mediterranean-DASH diet Intervention for Neurological Delay (MIND) diet and incidence of cognitive impairment have not been evaluated outside the United States.
METHODS:
We investigated MIND and Mediterranean diet relations with 12-year incidence of Alzheimer's disease/Vascular dementia (National Institute of Neurological Disorders criteria) and mild cognitive impairment (Winbald criteria) in the Personality and Total Health (PATH) Through Life cohort (n = 1220) set in Canberra, Australia: wave-1 2001-2002; wave-2 2005-2006; wave-3 2009-2010; and wave-4 2013-2014. MIND diet and two alternate Mediterranean diet scores were calculated from the baseline food frequency questionnaire responses. Higher dietary scores signified greater adherence.
RESULTS:
In adjusted logistic regression models, MIND diet (OR = 0.47, 95% CI 0.24, 0.91), but not Mediterranean diet, was associated with reduced odds of 12-year cognitive impairment.
DISCUSSION:
Preliminary evidence suggests that protective effects of the MIND diet are geographically generalizable. Additional prospective studies are needed in diverse samples to determine the relative effects of the MIND and the Mediterranean diets against cognitive decline.
KEYWORDS:
Alzheimer's disease; Cognitive impairment; Dietary pattern; Longitudinal cohort study; MIND diet; Mediterranean diet; Mild cognitive impairment

[AlPater]

Analysis of metabolites and metabolic pathways in breast cancer in a Korean prospective cohort: the Korean Cancer Prevention Study-II.
Yoo HJ, Kim M, Kim M, Kang M, Jung KJ, Hwang SM, Jee SH, Lee JH.
Metabolomics. 2018 Jun 8;14(6):85. doi: 10.1007/s11306-018-1382-4.
PMID: 30830383
https://sci-hub.tw/10.1007/s11306-018-1382-4
Abstract
INTRODUCTION:
Since blood is in contact with all tissues in the body and is considered to dynamically reflect the body's pathophysiological status, serum metabolomics changes are important and have diagnostic value in early cancer detection.
OBJECTIVES:
In this prospective study, we investigated the application of metabolomics to differentiate subjects with incident breast cancer (BC) from subjects who remained free of cancer during a mean follow-up period of 7 years with the aim of identifying valuable biomarkers for BC.
METHODS:
Baseline serum samples from 84 female subjects with incident BC (BC group) and 88 cancer-free female subjects (control group) were used. Metabolic alterations associated with BC were investigated via metabolomics analysis of the baseline serum samples using ultra-performance liquid chromatography-linear-trap quadrupole-Orbitrap mass spectrometry.
RESULTS:
A total of 57 metabolites were identified through the metabolic analysis. Among them, 20 metabolite levels were significantly higher and 22 metabolite levels were significantly lower in the BC group than in the control group at baseline. Ten metabolic pathways, including amino acid metabolism, arachidonic acid (AA) metabolism, fatty acid metabolism, linoleic acid metabolism, and retinol metabolism, showed significant differences between the BC group and the control group. Logistic regression revealed that the incidence of BC was affected by leucine, AA, prostaglandin (PG)J2, PGE2, and γ-linolenic acid (GLA).
CONCLUSIONS:
This prospective study showed the clinical relevance of dysregulation of various metabolisms on the incidence of BC. Additionally, leucine, AA, PGJ2, PGE2, and GLA were identified as independent variables affecting the incidence of BC.
KEYWORDS:
Breast cancer; Cohort; Early biomarkers; Metabolites; Metabolomics; Prospective study

Two days of calorie deprivation impairs high level cognitive processes, mood, and self-reported exertion during aerobic exercise: A randomized double-blind, placebo-controlled study.
Giles GE, Mahoney CR, Caruso C, Bukhari AS, Smith TJ, Pasiakos SM, McClung JP, Lieberman HR.
Brain Cogn. 2019 Mar 1;132:33-40. doi: 10.1016/j.bandc.2019.02.003. [Epub ahead of print]
PMID: 30831453
https://reader.elsevier.com/reader/sd/pii/S0278262618304597?token=710918DE45E0445AB18FEE1BD7240BFA390C681A02ECADF1E4FDCB182327278B8A79CF34F3E989BFA6303B2CC2BF9D84
Abstract
Military personnel and emergency responders perform cognitively-demanding tasks during periods of sustained physical exertion and limited caloric intake. Cognitive function is preserved during short-term caloric restriction, but it is unclear if preservation extends to combined caloric restriction and physical exertion. According to the "reticular-activating hypofrontality" model, vigorous exertion impairs prefrontal cortex activity and associated functions. This double-blind, placebo-controlled, crossover study examined cognitive function during sustained exertion while volunteers were calorically-deprived. Twenty-three volunteers were calorie-depleted for two days on one occasion and fully-fed on another. They completed intermittent bouts of exercise at 40-65% VO2peak while prefrontal cortex-dependent tasks of cognitive control, mood, and perceived exertion were assessed. Calorie deprivation impaired accuracy on the task-switching task of set-shifting (p < .01) and decreased sensitivity on the go/no-go task of response inhibition (p < .05). Calorie deprivation did not affect risk taking on the Rogers risk task. During exercise, calorie deprivation, particularly on day 2, increased perceived exertion (p < .05) and impaired mood states of tension, depression, anger, vigor, fatigue, and confusion (all p < .01). Physical exertion during severe calorie deprivation impairs cognitive control, mood, and self-rated exertion. Reallocation of cerebral metabolic resources from the prefrontal cortex to structures supporting movement may explain these deficits.
KEYWORDS:
Borg rating; Executive function; Military; Risk taking; Task-switching

Association between vegetarian diets and cardiovascular risk factors in non-Hispanic white participants of the Adventist Health Study-2.
Matsumoto S, Beeson WL, Shavlik DJ, Siapco G, Jaceldo-Siegl K, Fraser G, Knutsen SF.
J Nutr Sci. 2019 Feb 21;8:e6. doi: 10.1017/jns.2019.1. eCollection 2019.
PMID: 30828449
https://www.researchgate.net/publication/331251725_Association_between_vegetarian_diets_and_cardiovascular_risk_factors_in_non-Hispanic_white_participants_of_the_Adventist_Health_Study-2
Abstract
The association between dietary patterns and CVD risk factors among non-Hispanic whites has not been fully studied. Data from 650 non-Hispanic white adults who participated in one of two clinical sub-studies (about 2 years after the baseline) of the Adventist Health Study-2 (AHS-2) were analysed. Four dietary patters were identified using a validated 204-item semi-quantitative FFQ completed at enrolment into AHS-2: vegans (8·3 %), lacto-ovo-vegetarians (44·3 %), pesco-vegetarians (10·6 %) and non-vegetarians (NV) (37·3 %). Dietary pattern-specific prevalence ratios (PR) of CVD risk factors were assessed adjusting for confounders with or without BMI as an additional covariable. The adjusted PR for hypertension, high total cholesterol and high LDL-cholesterol were lower in all three vegetarian groups. Among the lacto-ovo-vegetarians the PR were 0·57 (95 % CI 0·45, 0·73), 0·72 (95 % CI 0·59, 0·88) and 0·72 (95 % CI 0·58, 0·89), respectively, which remained significant after additionally adjusting for BMI. The vegans and the pesco-vegetarians had similar PR for hypertension at 0·46 (95 % CI 0·25, 0·83) and 0·62 (95 % CI 0·42, 0·91), respectively, but estimates were attenuated and marginally significant after adjustment for BMI. Compared with NV, the PR of obesity and abdominal adiposity, as well as other CVD risk factors, were significantly lower among the vegetarian groups. Similar results were found when limiting analyses to participants not being treated for CVD risk factors, with the vegans having the lowest mean BMI and waist circumference. Thus, compared with the diet of NV, vegetarian diets were associated with significantly lower levels of CVD risk factors among the non-Hispanic whites.

Use of dietary supplements containing soy isoflavones and breast cancer risk among women aged >50 y: a prospective study.
Touillaud M, Gelot A, Mesrine S, Bennetau-Pelissero C, Clavel-Chapelon F, Arveux P, Bonnet F, Gunter M, Boutron-Ruault MC, Fournier A.
Am J Clin Nutr. 2019 Mar 4. pii: nqy313. doi: 10.1093/ajcn/nqy313. [Epub ahead of print]
PMID: 30831601
Abstract
BACKGROUND:
Soy-based dietary supplements have been promoted as natural alternatives to menopausal hormone therapy, but their potential effect on breast cancer development is controversial.
OBJECTIVES:
We examined the relation between the consumption of soy supplements and the risk of breast cancer, overall and by tumor hormone receptor status, among women aged >50 y.
METHODS:
In total, 76,442 women from the Etude Epidemiologique aupres de Femmes de la Mutuelle Generale de l'Education Nationale (E3N) cohort, born between 1925 and 1950, were followed from 2000 to 2011 (11.2 y on average, starting at a mean age of 59.5 y; 3608 incident breast cancers), with soy supplement use assessed every 2-3 y. HRs of breast cancer were estimated with the use of multivariable Cox models.
RESULTS:
Compared with never using soy supplements, the HRs associated with current use of soy supplements were 0.92 (95% CI: 0.76, 1.11) for all, 0.78 (95% CI: 0.60, 0.99) for estrogen receptor (ER)-positive, and 2.01 (95% CI: 1.41, 2.86) for ER-negative breast cancers. There was no association between past use of soy supplements and breast cancer. HRs for current use were 1.36 (95% CI: 0.95, 1.93) and 0.82 (95% CI: 0.65, 1.02) among women with and without a family history of breast cancer, respectively (P-interaction = 0.03) and 1.06 (95% CI: 0.87, 1.30) ≥5 y after menopause compared with 0.50 (95% CI: 0.31, 0.81) in premenopause or ≤5 y postmenopause (P-interaction = 0.04).
CONCLUSIONS:
In this cohort of women aged >50 y, we report opposing associations of soy supplements with ER-positive and ER-negative breast cancer risk. Our results also caution against the use of these supplements in women with a family history of breast cancer. Whether the risk profile of soy supplements could be more favorable among premenopausal or recently postmenopausal women deserves further investigation.
KEYWORDS:
breast cancer; cohort; dietary supplements; hormone receptors; isoflavones; prospective study; soy; women aged over 50 years

[AlPater]

Coffee consumption and plasma biomarkers of metabolic and inflammatory pathways in US health professionals.
Hang D, Kværner AS, Ma W, Hu Y, Tabung FK, Nan H, Hu Z, Shen H, Mucci LA, Chan AT, Giovannucci EL, Song M.
Am J Clin Nutr. 2019 Mar 5. pii: nqy295. doi: 10.1093/ajcn/nqy295. [Epub ahead of print]
PMID: 30834441
Abstract
BACKGROUND:
Coffee consumption has been linked to lower risk of various health outcomes. However, the biological pathways mediating the associations remain poorly understood.
OBJECTIVES:
The aim of this study was to assess the association between coffee consumption and concentrations of plasma biomarkers in key metabolic and inflammatory pathways underlying common chronic diseases.
METHODS:
We investigated the associations of total, caffeinated, and decaffeinated coffee consumption with 14 plasma biomarkers, including C-peptide, insulin-like growth factor 1 (IGF-1), IGF binding protein (IGFBP) 1, IGFBP-3, estrone, total and free estradiol, total and free testosterone, sex hormone-binding globulin (SHBG), total adiponectin, high-molecular-weight (HMW) adiponectin, leptin, C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor receptor 2 (sTNFR-2). Data were derived from 2 cohorts of 15,551 women (Nurses' Health Study) and 7397 men (Health Professionals Follow-Up Study), who provided detailed dietary data before blood draw and were free of diabetes, cardiovascular disease, or cancer at the time of blood draw. Multivariable linear regression was used to calculate the percentage difference of biomarker concentrations comparing coffee drinkers with nondrinkers, after adjusting for a variety of demographic, clinical, and lifestyle factors.
RESULTS:
Compared with nondrinkers, participants who drank ≥4 cups of total coffee/d had lower concentrations of C-peptide (-8.7%), IGFBP-3 (-2.2%), estrone (-6.4%), total estradiol (-5.7%), free estradiol (-8.1%), leptin (-6.4%), CRP (-16.6%), IL-6 (-8.1%), and sTNFR-2 (-5.8%) and higher concentrations of SHBG (5.0%), total testosterone (7.3% in women and 5.3% in men), total adiponectin (9.3%), and HMW adiponectin (17.2%). The results were largely similar for caffeinated and decaffeinated coffee.
CONCLUSIONS:
Our data indicate that coffee consumption is associated with favorable profiles of numerous biomarkers in key metabolic and inflammatory pathways.
KEYWORDS:
adipokine; coffee consumption; inflammation; insulin; sex hormone

Animal foods and postmenopausal breast cancer risk: a prospective cohort study.
Marcondes LH, Franco OH, Ruiter R, Ikram MA, Mulder M, Stricker BH, Kiefte-de Jong JC.
Br J Nutr. 2019 Mar 5:1-9. doi: 10.1017/S0007114519000072. [Epub ahead of print]
PMID: 30832747
Abstract
The role of diet on breast cancer risk is not well elucidated but animal food sources may play a role through, for example, the pathway of the insulin-like growth factor 1 system or cholesterol metabolism. The aim of this study was to evaluate the association between animal foods and the risk of postmenopausal breast cancer. This study was embedded in the Rotterdam Study, a population-based prospective cohort study of subjects aged 55 years and over (61 % female). Dietary intake of different animal foods was assessed at baseline using a validated FFQ and adjusted for energy intake using the residual method. We performed Cox proportional hazards modelling to analyse the association between the intake of the different food sources and breast cancer risk after adjustment for socio-demographic, lifestyle and metabolic factors. During a median follow-up of 17 years, we identified 199 cases of breast cancer (6·2 %) among 3209 women. After adjustment for multiple confounders, no consistent association was found between the intake of red meat intake, poultry, fish or dairy products and breast cancer risk. However, we found that egg intake was significantly associated with a higher risk of breast cancer (hazard ratioQ4 v. Q1: 1·83; 95 % CI 1·20, 2·79; P trend=0·01). In conclusion, this study found that dietary egg intake but no other animal foods was associated with a higher risk of postmenopausal breast cancer. Further research on the potential mechanisms underlying this association is warranted.
KEYWORDS:
HR hazard ratio; IGF-1 insulin-like growth factor 1; RS Rotterdam Study; Animal foods; Breast cancer; Cohort studies; Eggs

Statins for the Primary Prevention of Coronary Heart Disease.
Li M, Wang X, Li X, Chen H, Hu Y, Zhang X, Tang X, Miao Y, Tian G, Shang H.
Biomed Res Int. 2019 Jan 29;2019:4870350. doi: 10.1155/2019/4870350. eCollection 2019.
PMID: 30834266
Abstract
OBJECT:
The purpose of this study was to fully assess the role of statins in the primary prevention of coronary heart disease (CHD).
METHODS:
We searched six databases (PubMed, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journal Database) to identify relevant randomized controlled trials (RCTs) from inception to 31 October 2017. Two review authors independently assessed the methodological quality and analysed the data using Rev Man 5.3 software. Risk ratios and 95% confidence intervals (95% CI) were pooled using fixed/random-effects models. Funnel plots and Begg's test were conducted to assess publication bias. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS:
Sixteen RCTs with 69159 participants were included in this review. Statins can effectively decrease the occurrence of angina (RR=0.70, 95% CI: 0.58~0.85, I2 =0%), nonfatal myocardial infarction (MI) (RR=0.60, 95% CI: 0.51~0.69, I2 =14%), fatal MI (RR=0.49, 95% CI: 0.24~0.98, I2 =0%), any MI (RR=0.53, 95% CI: 0.42~0.67, I2 =0%), any coronary heart events (RR=0.73, 95% CI: 0.68~0.78, I2=0%), coronary revascularization (RR=0.66, 95% CI: 0.55~0.78, I2 = 0%), and any cardiovascular events (RR=0.77, 95% CI: 0.72~82, I2 = 0%). However, based on the current evidence, there were no significant differences in CHD deaths (RR=0.82, 95% CI: 0.66~1.02, I2=0%) and all-cause mortality (RR=0.88, 95% CI: 0.76 ~1.01, I2 =58%) between the two groups. Additionally, statins were more likely to result in diabetes (RR=1.21, 95% CI: 1.05~1.39, I2 =0%). There was no evidence of publication biases, and the quality of the evidence was considered moderate.
CONCLUSION:
Statins seemed to be beneficial for the primary prevention of CHDs but have no effect on CHD death and all-cause mortality.

Effects of krill oil and lean and fatty fish on cardiovascular risk markers: a randomised controlled trial.
Rundblad A, Holven KB, Bruheim I, Myhrstad MC, Ulven SM.
J Nutr Sci. 2018 Jan 17;7:e3. doi: 10.1017/jns.2017.64. eCollection 2018.
PMID: 29372051 Free PMC Article
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773922/pdf/S2048679017000647a.pdf
Abstract
Fish consumption and supplementation with n-3 fatty acids reduce CVD risk. Krill oil is an alternative source of marine n-3 fatty acids and few studies have investigated its health effects. Thus, we compared krill oil supplementation with the intake of fish with similar amounts of n-3 fatty acids on different cardiovascular risk markers. In an 8-week randomised parallel study, thirty-six healthy subjects aged 18-70 years with fasting serum TAG between 1·3 and 4·0 mmol/l were randomised to receive either fish, krill oil or control oil. In the fish group, subjects consumed lean and fatty fish, according to dietary guidelines. The krill and control group received eight capsules per d containing 4 g oil per d. The weekly intake of marine n-3 fatty acids from fish given in the fish group and from krill oil in the krill group were 4103 and 4654 mg, respectively. Fasting serum TAG did not change between the groups. The level of total lipids (P = 0·007), phospholipids (P = 0·015), cholesterol (P = 0·009), cholesteryl esters (P = 0·022) and non-esterified cholesterol (P = 0·002) in the smallest VLDL subclass increased significantly in response to krill oil supplementation. Blood glucose decreased significantly (P = 0·024) in the krill group and vitamin D increased significantly in the fish group (P = 0·024). Furthermore, plasma levels of marine n-3 fatty acids increased significantly in the fish and krill groups compared with the control (all P ≤ 0·0003). In conclusion, supplementation with krill oil and intake of fish result in health-beneficial effects. Although only krill oil reduced fasting glucose, fish provide health-beneficial nutrients, including vitamin D.
KEYWORDS:
DHA; DPA, docosapentaenoic acid; Docosapentaenoic acid; EPA; Fish; HOSO, high-oleic sunflower oil; IQR, interquartile range; Krill oil; Lipoprotein subclasses; TAG; XS-VLDL, smallest VLDL subclass

[AlPater]

Long-term coffee consumption, caffeine metabolism genetics, and risk of cardiovascular disease: a prospective analysis of up to 347,077 individuals and 8368 cases.
Zhou A, Hyppönen E.
Am J Clin Nutr. 2019 Mar 6. pii: nqy297. doi: 10.1093/ajcn/nqy297. [Epub ahead of print]
PMID: 30838377
Abstract
BACKGROUND:
Coffee is one of the most widely consumed stimulants worldwide and is generally considered to be safe or even beneficial for health. However, increased risk of myocardial infarction and hypertension has been suggested for individuals who carry a functional variant at cytochrome P450 1A2 (CYP1A2), which makes them less effective at metabolizing caffeine.
OBJECTIVES:
The aim of this study was to examine if the CYP1A2 genotype or a genetic score for caffeine metabolism (caffeine-GS) modifies the association between habitual coffee consumption and the risk of cardiovascular disease (CVD).
METHODS:
Genetic data and information on habitual coffee intake and relevant covariates were available for 347,077 individuals in the UK Biobank, including 8368 incident CVD cases. We used logistic regression to test for the association between coffee intake and CVD risk, and whether the association varies with CYP1A2 genotype or caffeine-GS.
RESULTS:
The association between habitual coffee intake and CVD risk was nonlinear, and, compared with participants drinking 1-2 cups/day, the risk of CVD was elevated for nondrinkers, drinkers of decaffeinated coffee, and those who reported drinking >6 cups/day (increase in odds by 11%, 7%, and 22%, respectively, P-curvature = 0.013). CYP1A2 genotype and caffeine-GS were not associated with CVD (P ≥ 0.22 for all comparisons). There was no evidence for an interaction between the CYP1A2 genotype or caffeine-GS and coffee intake with respect to risk of CVD (P ≥ 0.53).
CONCLUSIONS:
Heavy coffee consumption was associated with a modest increase in CVD risk, but this association was unaffected by genetic variants influencing caffeine metabolism.
KEYWORDS:
CYP1A2 ; UK Biobank; caffeine metabolism genetics; cardiovascular disease; gene-by-coffee interaction; habitual coffee consumption

Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential.
Madeo F, Carmona-Gutierrez D, Hofer SJ, Kroemer G.
Cell Metab. 2019 Mar 5;29(3):592-610. doi: 10.1016/j.cmet.2019.01.018. Review.
PMID: 30840912
https://sci-hub.tw/10.1016/j.cmet.2019.01.018
Abstract
The increase in life expectancy has boosted the incidence of age-related pathologies beyond social and economic sustainability. Consequently, there is an urgent need for interventions that revert or at least prevent the pathogenic age-associated deterioration. The permanent or periodic reduction of calorie intake without malnutrition (caloric restriction and fasting) is the only strategy that reliably extends healthspan in mammals including non-human primates. However, the strict and life-long compliance with these regimens is difficult, which has promoted the emergence of caloric restriction mimetics (CRMs). We define CRMs as compounds that ignite the protective pathways of caloric restriction by promoting autophagy, a cytoplasmic recycling mechanism, via a reduction in protein acetylation. Here, we describe the current knowledge on molecular, cellular, and organismal effects of known and putative CRMs in mice and humans. We anticipate that CRMs will become part of the pharmacological armamentarium against aging and age-related cardiovascular, neurodegenerative, and malignant diseases.
KEYWORDS:
AMPK; NAD; acetyl-CoA; acetyltransferases; aspirin; deacetylases; fasting; hydroxycitric acid; mTOR; metformin; nicotine adenine dinucleotide precursors; polyphenols; rapamycin; resveratrol; sirtuins; spermidine

n-3 Fatty acids and risk for fatal coronary disease.
Harris WS, Zotor FB.
Proc Nutr Soc. 2019 Mar 6:1-6. doi: 10.1017/S0029665118002902. [Epub ahead of print]
PMID: 30837013
Abstract
The purpose of this review is to consider the effects of the long-chain n-3 fatty acids found in marine foods, EPA and DHA, on risk for CVD, particularly fatal outcomes. It will examine both epidemiological and randomised controlled trial findings. The former studies usually examine associations between the dietary intake or the blood levels of EPA + DHA and CVD outcomes or, on occasion, total mortality. For example, our studies in the Framingham Heart Study and in the Women's Health Initiative Memory Study have demonstrated significant inverse relations between erythrocyte EPA + DHA levels (i.e. the Omega-3 Index) and total mortality. Recent data from the Cardiovascular Health Study reported the same relations between plasma phospholipid n-3 levels and overall healthy ageing. As regards randomised trials, studies in the 1990s and early 2000s were generally supportive of a cardiovascular benefit for fish oils (which contain EPA + DHA), but later trials were generally not able to duplicate these findings, at least for total CVD events. However, when restricted to effects on risk for fatal events, meta-analyses have shown consistent benefits for n-3 treatment. Taken together, the evidence is strong for a cardioprotective effect of EPA + DHA, especially when consumed in sufficient amounts to raise blood levels into healthy ranges. Establishing target EPA + DHA intakes to reduce risk for cardiovascular death is a high priority.
KEYWORDS:
FA fatty acid; RCT randomised controlled trial; Biomarkers; CVD; Controlled clinical trials; DHA; EPA; Epidemiology; Fish oil; Mortality

Does increasing meal frequency improve weight loss and some biochemical parameters in overweight/obese females?
Yildiran H, Mercanligil SM.
Nutr Hosp. 2018 Jul 11. doi: 10.20960/nh.2191. [Epub ahead of print]
PMID: 30836763
[See https://www.nutricionhospitalaria.org/articles/02191/show#! for pdf.]
Abstract
INTRODUCTION:
despite the positive effects of frequent meals on obesity treatment, there have been no definite conclusions on the matter.
OBJECTIVE:
the aim of this study is to determine the effects of different meal frequencies on weight loss, body composition and some biochemical parameters of overweight or obese females.
METHODS:
sixty-five adult overweight or obese females were recruited from the Endocrine Department of Ankara Gülhane Education and Research Hospital. Individualistic weight-loss diet programs were implemented (three meals/day for one group and six meals/day for the other group) with a three-month follow-up. Anthropometric measurements and 24-hour dietary records were taken for each week during the study period. Some biochemical parameters (lipid profile, fasting blood glucose, fasting insulin) were analyzed at the beginning and at the end of the study.
RESULTS:
forty-three participants finished the study period. Body weight, body mass index, fat mass (kg), fat mass percentage (%), and waist circumference (cm) decreased significantly in both groups (p < 0.05), while fat free mass (kg) and body water (l) did not change significantly (p > 0.05). Only serum fasting insulin levels decreased significantly in the six meals/day group (p < 0.05). Whatever the differences between the initial and final values of body weight, body composition, and biochemical parameters, they were similar between the groups (p > 0.05). Only the decrease in fasting insulin levels in the six-meal group was found higher than that of the three-meal group.
CONCLUSION:
in conclusion, body weight, body composition, and lipid profiling are not affected by the number of meals when weight-loss diets are prepared with adequate energy restrictions and sufficient and balanced nutrition.

Seize the Day for a Day With No Seizures: Modifiable Midlife Risk Factors Identified.
Koubeissi M.
Epilepsy Curr. 2019 Jan;19(1):27-28. doi: 10.1177/1535759718822041. Epub 2019 Jan 30.
PMID: 30838917
Abstract
Importance: The incidence of epilepsy is higher in older age than at any other period of life. Stroke, dementia, and hypertension are associated with late-onset epilepsy; however, the role of other vascular and lifestyle factors remains unclear.
OBJECTIVE:
To identify midlife vascular and lifestyle risk factors for late-onset epilepsy.
DESIGN, SETTING, AND PARTICIPANTS:
The Atherosclerosis Risk in Communities (ARIC) study is a prospective cohort study of 15 792 participants followed up since 1987 to 1989 with in-person visits, telephone calls, and surveillance of hospitalizations (10 974 invited without completing enrollment). The ARIC is a multicenter study with participants selected from 4 US communities. This study included 10 420 black or white participants from ARIC with at least 2 years of Medicare fee-for-service coverage and without missing baseline data. Data were analyzed between April 2017 and May 2018. Exposures: Demographic, vascular, lifestyle, and other possible epilepsy risk factors measured at baseline (age 45-64 years) were evaluated in multivariable survival models including demographics, vascular risk factors, and lifestyle risk factors. Main Outcomes and Measures: Time to development of late-onset epilepsy (2 or more International Classification of Diseases, Ninth Revision codes for epilepsy or seizures starting at 60 years or older in any claim [hospitalization or outpatient Medicare through 2013]), with first code for seizures after at least 2 years without code for seizures.
RESULTS:
Of the 10 420 total participants (5878 [56.4%] women and 2794 [26.8%] black participants; median age 55 years at first visit), 596 participants developed late-onset epilepsy (3.33 per 1000 person-years). The incidence was higher in black than in white participants (4.71; 95% confidence interval [CI], 4.12-5.40 vs 2.88; 95% CI, 2.60-3.18 per 1000 person-years). In multivariable analysis, baseline hypertension (hazard ratio {HR}, 1.30; 95% CI, 1.09-1.55), diabetes (HR, 1.45; 95% CI, 1.17-1.80), smoking (HR, 1.09; 95% CI, 1.01-1.17), apolipoprotein E ε4 (APOE ε4) genotype (1 allele HR, 1.22; 95% CI, 1.02-1.45; 2 alleles HR, 1.95; 95% CI, 1.35-2.81), incident stroke (HR, 3.38; 95% CI, 2.78-4.10), and dementia (HR, 2.56; 95% CI, 2.11-3.12) were associated with an increased risk of late-onset epilepsy, while higher levels of physical activity (HR, 0.90; 95% CI, 0.83-0.98) and moderate alcohol intake (HR, 0.72; 95% CI, 0.57-0.90) were associated with a lower risk. Results were similar after censoring individuals with stroke or dementia.
CONCLUSIONS AND RELEVANCE:
Potentially modifiable risk factors in midlife and the APOE ε4 genotype were positively associated with risk of developing late-onset epilepsy. Although stroke and dementia were both associated with late-onset epilepsy, vascular and lifestyle risk factors were significant even in the absence of stroke or dementia.

Edited March 7, 2019 by AlPater

[AlPater]

Methionine restriction prevents onset of type 2 diabetes in NZO mice.
Castaño-Martinez T, Schumacher F, Schumacher S, Kochlik B, Weber D, Grune T, Biemann R, McCann A, Abraham K, Weikert C, Kleuser B, Schürmann A, Laeger T.
FASEB J. 2019 Mar 6:fj201900150R. doi: 10.1096/fj.201900150R. [Epub ahead of print]
PMID: 30841758
Abstract
Dietary methionine restriction (MR) is well known to reduce body weight by increasing energy expenditure (EE) and insulin sensitivity. An elevated concentration of circulating fibroblast growth factor 21 (FGF21) has been implicated as a potential underlying mechanism. The aims of our study were to test whether dietary MR in the context of a high-fat regimen protects against type 2 diabetes in mice and to investigate whether vegan and vegetarian diets, which have naturally low methionine levels, modulate circulating FGF21 in humans. New Zealand obese (NZO) mice, a model for polygenic obesity and type 2 diabetes, were placed on isocaloric high-fat diets (protein, 16 kcal%; carbohydrate, 52 kcal%; fat, 32 kcal%) that provided methionine at control (Con; 0.86% methionine) or low levels (0.17%) for 9 wk. Markers of glucose homeostasis and insulin sensitivity were analyzed. Among humans, low methionine intake and circulating FGF21 levels were investigated by comparing a vegan and a vegetarian diet to an omnivore diet and evaluating the effect of a short-term vegetarian diet on FGF21 induction. In comparison with the Con group, MR led to elevated plasma FGF21 levels and prevented the onset of hyperglycemia in NZO mice. MR-fed mice exhibited increased insulin sensitivity, higher plasma adiponectin levels, increased EE, and up-regulated expression of thermogenic genes in subcutaneous white adipose tissue. Food intake and fat mass did not change. Plasma FGF21 levels were markedly higher in vegan humans compared with omnivores, and circulating FGF21 levels increased significantly in omnivores after 4 d on a vegetarian diet. These data suggest that MR induces FGF21 and protects NZO mice from high-fat diet-induced glucose intolerance and type 2 diabetes. The normoglycemic phenotype in vegans and vegetarians may be caused by induced FGF21. MR akin to vegan and vegetarian diets in humans may offer metabolic benefits via increased circulating levels of FGF21 and merits further investigation.
KEYWORDS:
energy expenditure; hyperglycemia; obesity; vegan; vegetarian

Chronic conditions and multimorbidity in population aged 90 years and over: associations with mortality and long-term care admission.
Halonen P, Raitanen J, Jämsen E, Enroth L, Jylhä M.
Age Ageing. 2019 Mar 7. pii: afz019. doi: 10.1093/ageing/afz019. [Epub ahead of print]
PMID: 30843581
https://sci-hub.tw/10.1093/ageing/afz019
Abstract
BACKGROUND:
prevalence of many chronic conditions is rising in the aging population worldwide. However, the long-term impact of these conditions and multimorbidity on other health outcomes in very old age is rarely studied.
METHODS:
the data were based on four waves of the Vitality 90+ Study conducted in 2001, 2003, 2007 and 2010. Associations of chronic conditions and multimorbidity with mortality were analysed in a total sample of 2,862 people aged over 90, and associations with long-term care (LTC) admission in a subsample of 1,954 participants living at home in baseline. Risk of death and LTC admission were assessed with Cox and competing risks regression with time-dependent covariates. Population attributable fractions (PAF) for mortality and LTC admission were calculated for chronic conditions based on the regression models.
RESULTS:
heart disease, diabetes and dementia predicted mortality in men and women. In addition, depression was associated with increased mortality in women. Parkinson's disease, dementia and hip fracture predicted LTC admission in women. Multimorbidity increased the risk of death and LTC admission in women but not in men. For both genders, dementia had the highest PAF for mortality and LTC admission.
CONCLUSION:
heart disease and diabetes are still important predictors of mortality in very old age. However, the role of dementia is pronounced in this age group. Of the studied conditions, dementia is the main contributor both to mortality and LTC admission. Multimorbidity has predictive value concerning both mortality and LTC admission, at least in oldest old women.
KEYWORDS:
chronic conditions; long-term care; mortality; multimorbidity; nonagenarians; older people

Fruit, vegetable intake and blood pressure trajectories in older age.
Stefler D, Malyutina S, Nikitin Y, Nikitenko T, Rodriguez-Artalejo F, Peasey A, Pikhart H, Sabia S, Bobak M.
J Hum Hypertens. 2019 Mar 6. doi: 10.1038/s41371-019-0189-8. [Epub ahead of print]
PMID: 30842546
https://www.nature.com/articles/s41371-019-0189-8.pdf
Abstract
Diet rich in fruits and vegetables (F&V) is an established protective factor for hypertension, but the available evidence regarding the impact of F&V consumption on age-related blood pressure change is limited. We examined whether systolic (SBP) and diastolic (DBP) blood pressure trajectories are influenced by F&V intakes in an ageing Russian cohort. Dietary data was available for 8997 men and women in the Health, Alcohol and Psychosocial Factors in Eastern Europe prospective cohort study. Blood pressure measurements were taken at three time-points over 12 years of follow-up, during which time the mean age of the sample changed from 58 to 69 years. The relationships between F&V intake and SBP and DBP were assessed using mixed-effect multilevel models. In the multivariable adjusted models, fruit intake was inversely related to both systolic and diastolic blood pressure at baseline (mean SBP and DBP was 3.5 mmHg and 1.4 mm Hg lower in the highest compared to the lowest intake tertiles, respectively (both p values < 0.001)). However, it was not associated with blood pressure change over time (difference in annual SBP and DBP change was 0.11 mmHg (p value = 0.138) and 0.01 mmHg (p value = 0.894), respectively). We found no significant link between vegetable intake and blood pressure, neither cross-sectionally nor longitudinally. In addition to the association with diet, we observed increasing SBP and mostly steady DBP over age, with deceleration and downward turn after the ages of 55-59 years. On the whole, this analysis found no consistent association between F&V intake and trajectories of blood pressure in older age.

[AlPater]

Association of Leisure-Time Physical Activity Across the Adult Life Course With All-Cause and Cause-Specific Mortality.
Saint-Maurice PF, Coughlan D, Kelly SP, Keadle SK, Cook MB, Carlson SA, Fulton JE, Matthews CE.
JAMA Netw Open. 2019 Mar 1;2(3):e190355. doi: 10.1001/jamanetworkopen.2019.0355.
PMID: 30848809
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2727269
Abstract
IMPORTANCE:
Although the benefits of leisure-time physical activity (LTPA) in middle age are established, the health effects of long-term participation and changes in LTPA between adolescence and middle age have not been documented.
OBJECTIVE:
To determine whether an association exists between LTPA life course patterns and mortality.
DESIGN, SETTING, AND PARTICIPANTS:
This prospective cohort study used data from the National Institutes of Health-AARP (formerly American Association of Retired Persons) Diet and Health Study established in 1995 to 1996. Data analysis was conducted from March 2017 through February 2018. Data were analyzed for 315 059 adult AARP members living in 6 states, namely, California, Florida, Louisiana, New Jersey, North Carolina, or Pennsylvania, or 2 metropolitan areas, Atlanta, Georgia, or Detroit, Michigan.
EXPOSURES:
Self-reported LTPA (hours per week) at the baseline interview for ages grouped as 15 to 18, 19 to 29, 35 to 39, and 40 to 61 years.
MAIN OUTCOMES AND MEASURES:
All-cause, cardiovascular disease (CVD)-related, and cancer-related mortality records available through December 31, 2011.
RESULTS:
Of 315 059 participants, 183 451 (58.2%) were men, and the participants were 50 to 71 years of age at enrollment. Ten LTPA trajectories (categorized as maintaining, increasing, and decreasing LTPA across time) were identified, and 71 377 deaths due to all causes, 22 219 deaths due to CVD, and 16 388 deaths due to cancer occurred. Compared with participants who were consistently inactive throughout adulthood, participants who maintained the highest amount of LTPA in each age period were at lower risks for all-cause, CVD-related, and cancer-related mortality. For example, compared with participants who were consistently inactive, maintaining higher amounts of LTPA was associated with lower all-cause (hazard ratio {HR}, 0.64; 95% CI, 0.60-0.68), CVD-related (HR, 0.58; 95% CI, 0.53-0.64), and cancer-related (HR, 0.86; 95% CI, 0.77-0.97) mortality. Adults who were less active throughout most of the adult life course but increased LTPA in later adulthood (40-61 years of age) also had lower risk for all-cause (HR, 0.65; 95% CI, 0.62-0.68), CVD-related (HR, 0.57; 95% CI, 0.53-0.61), and cancer-related (HR, 0.84; 95% CI, 0.77-0.92) mortality.
CONCLUSIONS AND RELEVANCE:
Maintaining higher LTPA levels and increasing LTPA in later adulthood were associated with comparable low risk of mortality, suggesting that midlife is not too late to start physical activity. Inactive adults may be encouraged to be more active, whereas young adults who are already active may strive to maintain their activity level as they get older.

Dietary calcium intake and the risk of metabolic syndrome: evidence from observational studies.
Cheng L, Hu D, Jiang W.
Public Health Nutr. 2019 Mar 8:1-8. doi: 10.1017/S1368980019000247. [Epub ahead of print]
PMID: 30846011
Abstract
OBJECTIVE:
Epidemiological investigations evaluating the association of dietary Ca intake with metabolic syndrome (MetS) risk have yielded controversial results. Therefore, a meta-analysis was conducted to quantitatively summarize the association between dietary Ca intake and the risk of MetS.
DESIGN:
PubMed, Embase and Web of Science were searched for relevant articles published up to October 2018. The pooled OR and 95 % CI were calculated with a random-effects model.
SETTING:
Meta-analysis.ParticipantsNine cross-sectional studies.
RESULTS:
A total of nine articles with fifteen studies for dietary Ca intake were finally included in the meta-analysis. The combined OR with 95 % CI of MetS for the highest v. lowest category of dietary Ca intake was 0·80 (95 % CI 0·70, 0·91). For dose-response analysis, a non-linear relationship was found between dietary intake of Ca and risk of MetS (P non-linearity&lt;0·001). The threshold for dietary Ca intake was 280 mg/d (OR=0·87; 95 % CI 0·82, 0·93), reducing the risk of MetS by 13 %.
CONCLUSIONS:
The present meta-analysis suggests that dietary Ca intake might reduce the risk of MetS, which needs to be further confirmed by larger prospective cohort studies.
KEYWORDS:
Calcium; Dietary; Meta-analysis; Metabolic syndrome

Effect of vitamin E supplementation on blood pressure: a systematic review and meta-analysis.
Emami MR, Safabakhsh M, Alizadeh S, Asbaghi O, Khosroshahi MZ.
J Hum Hypertens. 2019 Mar 7. doi: 10.1038/s41371-019-0192-0. [Epub ahead of print]
PMID: 30846828
Abstract
Although emerging evidence suggests that vitamin E may contribute to blood pressure improvement, the effects of vitamin E on systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) are still controversial. The aim was to evaluate the influence of vitamin E on SBP, DBP, and MAP through meta-analysis. We identified all studies that assessed the effect of vitamin E supplementation on SBP, DBP, and MAP from PubMed/Medline, SCOPUS, and Google scholar up to March 2018. Weighted mean differences (WMD) and 95% confidence interval (CI) were expressed as effect size. Pre-specified subgroup analysis was conducted to evaluate potential sources of heterogeneity. Meta-regression analyses were performed to investigate association between blood pressure-lowering effects of vitamin E and duration of follow-up and dose of treatment. Eighteen trials, comprising 839 participants met the eligibility criteria. Results of this study showed that compared to placebo, SBP decreased significantly in vitamin E group (WMD = -3.4 mmHg, 95% CI = -6.7 to -0.11, P < 0.001), with a high heterogeneity across the studies (I2 = 94.0%, P < 0.001). Overall, there were no significant effects on DBP and MAP. This meta-analysis suggested that vitamin E supplements decreased only SBP and had no favorable effect on DBP and MAP.

Protein supplementation improves lean body mass in physically active older adults: a randomized placebo-controlled trial.
Ten Haaf DSM, Eijsvogels TMH, Bongers CCWG, Horstman AMH, Timmers S, de Groot LCPGM, Hopman MTE.
J Cachexia Sarcopenia Muscle. 2019 Mar 7. doi: 10.1002/jcsm.12394. [Epub ahead of print]
PMID: 30848096
https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcsm.12394
Abstract
BACKGROUND:
An inadequate protein intake may offset the muscle protein synthetic response after physical activity, reducing the possible benefits of an active lifestyle for muscle mass. We examined the effects of 12 weeks of daily protein supplementation on lean body mass, muscle strength, and physical performance in physically active older adults with a low habitual protein intake (<1.0 g/kg/day).
METHODS:
A randomized double-blinded controlled trial was performed among 116 physically active older adults [age 69 (interquartile range: 67-73) years, 82% male] who were training for a 4 day walking event of 30, 40, or 50 km/day. Participants were randomly allocated to either 31 g of milk protein or iso-caloric placebo supplementation for 12 weeks. Body composition (dual-energy X-ray absorptiometry), strength (isometric leg extension and grip strength), quadriceps contractile function, and physical performance [Short Physical Performance Battery, Timed Up-and-Go test, and cardiorespiratory fitness (Åstrand-Rhyming submaximal exercise test)] were measured at baseline and after 12 weeks. We assessed vitamin D status and markers of muscle damage and renal function in blood and urine samples before and after intervention.
RESULTS:
A larger increase in relative lean body mass was observed in the protein vs. placebo group (∆0.93 ± 1.22% vs. ∆0.44 ± 1.40%, PInteraction  = 0.046). Absolute and relative fat mass decreased more in the protein group than in the placebo group (∆-0.90 ± 1.22 kg vs. ∆-0.31 ± 1.28 kg, PInteraction  = 0.013 and ∆-0.92 ± 1.19% vs. ∆-0.39 ± 1.36%, PInteraction  = 0.029, respectively). Strength and contractile function did not change in both groups. Gait speed, chair-rise ability, Timed Up-and-Go, and cardiorespiratory fitness improved in both groups (P < 0.001), but no between-group differences were observed. Serum urea increased in the protein group, whereas no changes were observed in the placebo group (PInteraction  < 0.001). No between-group differences were observed for vitamin D status, muscle damage, and renal function markers.
CONCLUSIONS:
In physically active older adults with relatively low habitual dietary protein consumption, an improvement in physical performance, an increase in lean body mass, and a decrease in fat mass were observed after walking exercise training. A larger increase in relative lean body mass and larger reduction in fat mass were observed in participants receiving 12 weeks of daily protein supplementation compared with controls, whereas this was not accompanied by differences in improvements between groups in muscle strength and physical performance.
KEYWORDS:
Body composition; Elderly; Muscle; Protein; Randomized clinical trial

Edited March 9, 2019 by AlPater

[AlPater]

THE EFFECT OF VEGAN DIETS ON BLOOD PRESSURE IN ADULTS: A META-ANALYSIS OF RANDOMIZED, CONTROLLED TRIALS.
Lopez PD, Cativo EH, Atlas SA, Rosendorff C.
Am J Med. 2019 Mar 6. pii: S0002-9343(19)30171-8. doi: 10.1016/j.amjmed.2019.01.044. [Epub ahead of print]
PMID: 30851264
Abstract
BACKGROUND:
Vegan diets are increasing in popularity and have beneficial effects on glycemia and blood lipids, but the evidence is inconclusive regarding their effect on blood pressure. The purpose of this study was to review the effect of vegan diets on blood pressure in adults.
METHODS:
We searched MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov for records that compared a vegan diet to any less restrictive diet and reported pre- and post-intervention systolic and diastolic blood pressures. Two reviewers independently screened abstracts for randomized, controlled clinical trials in individuals ≥18years of age and older. We used the PRISMA guidelines to select 11 clinical trials from 1673 records. Data synthesis was performed through a random-effects model.
RESULTS:
The pooled data included 983 participants. Compared to less restrictive diets, a vegan diet did not result in a significant change in systolic (-1.33mmHg; 95% CI -3.50 to 0.84; p=0.230) or diastolic (-1.21mmHg; 95% CI -3.06 to 0.65; p=0.203) blood pressure. A pre-specified subgroup analysis of studies with baseline systolic blood pressure≥130mmHg revealed that a vegan diet resulted in a mean decrease in the systolic (-4.10mmHg; 95% CI -8.14 to -0.06; p=0.047) and diastolic (-4.01mmHg; 95% CI -5.97 to -2.05; p=0.000) blood pressures.
CONCLUSION:
The changes in blood pressure induced by a vegan diet without caloric restrictions are comparable to those induced by dietary approaches recommended by medical societies and portion-controlled diets.
KEYWORDS:
blood pressure; vegan diet; veganism

Alcohol Consumption and Incident Kidney Disease: Results From the Atherosclerosis Risk in Communities Study.
Hu EA, Lazo M, Rosenberg SD, Grams ME, Steffen LM, Coresh J, Rebholz CM.
J Ren Nutr. 2019 Mar 5. pii: S1051-2276(19)30029-9. doi: 10.1053/j.jrn.2019.01.011. [Epub ahead of print]
PMID: 30850190
Abstract
OBJECTIVE(S):
Moderate alcohol consumption has been found to be associated with lower risk of coronary heart disease and myocardial infarction, which share similar risk factors and pathophysiology with chronic kidney disease (CKD). However, there is inconsistent evidence on the association between alcohol consumption and CKD.
DESIGN AND METHODS:
We conducted a prospective analysis of 12,692 participants aged 45-64 years from the Atherosclerosis Risk in Communities (ARIC) study. We categorized participants into 6 alcohol consumption categories: never drinkers, former drinkers, ≤1 drink per week, 2 to 7 drinks per week, 8 to 14 drinks per week, and ≥15 drinks per week based on food frequency questionnaire responses at visit 1 (1987-1989). Incident CKD was defined as estimated glomerular filtration rate <60 mL/minute/1.73 m2 accompanied by ≥25% estimated glomerular filtration rate decline, a kidney disease-related hospitalization or death or end-stage renal disease.
RESULTS:
During a median follow-up of 24 years, there were 3,664 cases of incident CKD. Current drinkers were more likely to be men, whites, and to have a higher income level and education level. After adjusting for total energy intake, age, sex, race-center, income, education level, health insurance, smoking, and physical activity, there was no significant association between being a former drinker and risk of incident CKD. Participants who drank ≤1 drink per week, 2 to 7 drinks per week, 8 to 14 drinks per week, and ≥15 drinks per week had, respectively, a 12% (hazard ratio

---

: 0.88, 95% confidence interval [CI]: 0.79-0.97), 20% (HR: 0.80, 95% CI: 0.72-0.89), 29% (HR: 0.71, 95% CI: 0.62-0.83), and 23% (HR: 0.77, 95% CI: 0.65-0.91) lower risk of CKD compared with never drinkers.
CONCLUSION(S):
Consuming a low or moderate amount of alcohol may lower the risk of developing CKD. Therefore, moderate consumption of alcohol may not likely be harmful to the kidneys.

Association between PUFA intake and serum concentration and mortality in older adults: A cohort study.
Lelli D, Antonelli Incalzi R, Ferrucci L, Bandinelli S, Pedone C.
Clin Nutr. 2019 Feb 23. pii: S0261-5614(19)30084-6. doi: 10.1016/j.clnu.2019.02.030. [Epub ahead of print]
PMID: 30850268
Abstract
BACKGROUND & AIMS:
PUFA intake is associated with reduced cardiovascular and all-cause mortality in the general population; however, evidence about this association in older adults is controversial. The objective of this study was to evaluate the relationship between PUFA intake and serum concentration, and the association of these variables with all-cause and cardiovascular mortality.
METHODS:
in this cohort study, we selected 927 community dwelling adults aged ≥65 years enrolled in the InCHIANTI study from 1998 to 2000 and followed-up for 9 years. The association between PUFA intake and serum concentration was evaluated using scatterplot and Pearson correlation test; all-cause and cardiovascular mortality was analyzed using the Kaplan-Meier method and Cox regressions adjusted for potential confounders.
RESULTS:
mean age of the population was 75 years (SD 7.3), 55% were women. There was no association between overall PUFAs, linolenic and linoleic acid intake and their serum concentration. There was no association between quartiles (Q) of PUFA intake and all-cause mortality: compared to Q1 of PUFA intake, the adjusted HR (95% CI) for overall mortality were: 1.05 (0.74-1.50) in Q2, 1.10 (0.76-1.58) in Q3, and 0.98 (0.68-1.41) in Q4; this lack of association was confirmed for cardiovascular mortality. Compared to Q1, participants in the fourth quartile of PUFA serum concentration had lower risk of all-cause mortality (adjusted HR [95%CI]: Q2 1.10 [0.79-1.53], Q3 0.84 [0.60-1.19], Q4 0.66 [0.44-0.995]), no association was found for cardiovascular mortality.
CONCLUSIONS:
In our sample of community-dwelling older adults, PUFA intake is not associated with PUFA serum concentration. Interventions to modulate PUFA concentration based on dietary intake may not be effective in preventing mortality in this population.
KEYWORDS:
Aged; Diet; Linoleic acid; Linolenic acid; Mortality; Polyunsaturated fatty acids

Association Between Nitrite and Nitrate Intake and Risk of Gastric Cancer: A Systematic Review and Meta-Analysis.
Zhang FX, Miao Y, Ruan JG, Meng SP, Dong JD, Yin H, Huang Y, Chen FR, Wang ZC, Lai YF.
Med Sci Monit. 2019 Mar 9;25:1788-1799. doi: 10.12659/MSM.914621.
PMID: 30850575
Abstract
BACKGROUND Studies have shown inconsistent associations of nitrite and nitrate intake with the risk of gastric cancer or its associated mortality. We performed a meta-analysis of observational studies to evaluate the correlation of nitrite and nitrate intake with the risk of gastric cancer. MATERIAL AND METHODS We searched for studies reporting effect estimates and 95% confidence intervals (CIs) of gastric cancer in PubMed, EMBASE, and the Cochrane Library through November 2018. The summary results of the included studies were pooled using a random-effects model. RESULTS Eighteen case-control and 6 prospective cohort studies recruiting 800 321 participants were included in this study. The summary results indicated that the highest (odds ratio [OR], 1.27; 95%CI, 1.03-1.55; P=0.022) or moderate (OR: 1.12; 95%CI, 1.01-1.26; P=0.037) nitrite intake were associated with a higher risk of gastric cancer. However, we noted that high (OR, 0.81; 95%CI, 0.68-0.97; P=0.021) or moderate (OR, 0.86; 95%CI, 0.75-0.99; P=0.036) nitrate intakes were associated with a reduced risk of gastric cancer. These associations differed when stratified by publication year, study design, country, the percentage of male participants, assessment of exposure, adjusted model, and study quality. CONCLUSIONS High or moderate nitrite intake was associated with higher risk of gastric cancer, whereas high or moderate nitrate intake was correlated with lower risk of gastric cancer.

[AlPater]

Prediabetes diagnosis criteria, type 2 diabetes risk and dietary modulation: The CORDIOPREV study.
Roncero-Ramos I, Alcala-Diaz JF, Rangel-Zuñiga OA, Gomez-Delgado F, Jimenez-Lucena R, García-Rios A, Vals-Delgado C, Romero-Baldonado C, Luque RM, Ordovas JM, Perez-Martinez P, Camargo A, Lopez-Miranda J.
Clin Nutr. 2019 Feb 21. pii: S0261-5614(19)30081-0. doi: 10.1016/j.clnu.2019.02.027. [Epub ahead of print]
PMID: 30852029
Abstract
AIM:
Our objective was to investigate the role of two healthy diets in modulating the risk of type 2 diabetes (T2DM) development associated with each prediabetes diagnosis criteria in coronary heart disease patients. Additionally, we explored the pathophysiological characteristics and the risk of developing T2DM in patients with different prediabetes criteria.
METHODS:
We included 462 patients from the CORDIOPREV study without T2DM at baseline: 213 had prediabetes defined by impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) (PreDM-IFG/IGT); 180 had prediabetes by isolated hemoglobin glycated plasma levels (PreDM-isolated-HbA1c), and 69 were not prediabetics (non-PreDM), according to the American Diabetes Association criteria. Patients were randomized to consume either a Mediterranean or a low-fat diet. We performed a COX proportional hazards regression analysis to determine the T2DM risk according to diet and the prediabetes criteria after a median follow-up of 60 months.
RESULTS:
We found higher T2DM risk (HR: 2.98; 95% CI 1.27-6.98) in PreDM-IFG/IGT than in PreDM-isolated-HbA1c (HR: 2.31; 95% CI 0.97-5.49) compared with non-PreDM. Long-term consumption of a low-fat diet was associated with a lower risk of T2DM when compared to the Mediterranean diet in the PreDM-IFG/IGT group (HR: 3.20; 95% CI 0.75-13.69 versus HR: 4.70; 95% CI 1.12-19.67, respectively). Moreover, we found the highest risk of T2DM development associated with patients who had both IFG and IGT (HR: 2.15; 95% CI 1.11-4.16). Patients who had both IFG and IGT and consumed a low-fat diet had a lower T2DM risk than those who consumed a Mediterranean diet (HR: 1.53; 95% CI 0.53-4.39 versus HR: 3.33; 95% CI 1.34-8.30, respectively).
CONCLUSION:
Our results suggest that the type of diet consumed may modulate the risk of T2DM development according to the prediabetes diagnosis criteria. Specifically, our study showed that the consumption of a low-fat diet was more beneficial than a Mediterranean diet in patients with IFG and IGT.
KEYWORDS:
CORDIOPREV; Diabetes; Diet; Disease prediction; Prediabetes

[AlPater]

Effects of Melatonin Supplementation On Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Hadi A, Ghaedi E, Moradi S, Pourmasoumi M, Ghavami A, Kafeshani M.
Horm Metab Res. 2019 Mar;51(3):157-164. doi: 10.1055/a-0841-6638. Epub 2019 Mar 12.
PMID: 30861561
Abstract
Melatonin is a physiological indoleamine secreted from the pineal gland into the bloodstream. This hormone has antioxidant effects in cardiovascular disease, but the evidence regarding its effects on blood pressure (BP) has not been conclusive. Therefore, we assessed the impact of melatonin supplementation on systolic BP (SBP) and diastolic BP (DBP) through a systematic review and meta-analysis of available randomized controlled trials (RCTs). Medline, Scopus, Web of Science, Cochrane library, and Google scholar (until May 2018) were searched to identify potential RCTs with information on melatonin supplementation and BP. Mean Differences (MD) were pooled using a random-effects model. Standard methods were used for assessment of heterogeneity, sensitivity analysis, and publication bias. Pooling 5 RCTs (6 treatment arms) together identified significant reduction for SBP (MD: -3.43 mmHg, 95% confidence interval (CI): -5.76 to -1.09, p=0.004) and DBP (MD: -3.33 mmHg, 95% CI: -4.57 to -2.08, p<0.001) after supplementation with melatonin compared with control treatment. The sensitivity analysis indicated that the results were robust. We did not observe any evidence regarding publication bias. The findings of this meta-analysis support the overall favorable effect of melatonin supplementation on BP regulation.

Widespread pain is a risk factor for cardiovascular mortality: results from the Framingham Heart Study.
Tesarz J, Eich W, Baumeister D, Kohlmann T, D'Agostino R, Schuster AK.
Eur Heart J. 2019 Mar 11. pii: ehz111. doi: 10.1093/eurheartj/ehz111. [Epub ahead of print]
PMID: 30859195
https://sci-hub.tw/10.1093/eurheartj/ehz111
Abstract
AIMS:
With the introduction of widespread pain (WSP) as a separate diagnostic code in the ICD-11, WSP has now become an own clinical diagnosis independent of the underlying pathophysiology. Research has reported aetiological associations of WSP and cardiovascular diseases. However, studies on mortality risk in individuals with WSP have reported inconsistent results. This study investigates whether there is increased mortality in WSP individuals and establish potential determinants of mortality risk. Therefore, we evaluates the population-based prospective cohort of the Framingham Heart Study (FHS).
METHODS AND RESULTS:
The FHS is a longitudinal multi-generational study. Pain status was assessed uniquely between 1990 and 1994. Cox proportional hazards modelling was used to estimate hazard ratios (HRs) of WSP on all-cause mortality controlling for sex and age, cardiovascular risk factors, cancer history, lifestyle factors and current medication. WSP examination was carried out in 4746 participants of the FHS (60.3 ± 13.5 years, 55.1% women). A total of 678 (14.5%) subjects fulfilled the criteria for WSP, whereas 4011 (85.5%) subjects did not. The follow-up time was 15 years, during which 202 persons died in the WSP group and 1144 in the no-WSP group. When adjusting for age and sex, all-cause mortality was increased by about 16% in WSP subjects. Individuals with WSP had an increased HR particularly for cardiovascular cause of death (HR adjusted by age and sex = 1.46, 95% confidence interval 1.10-1.94).
CONCLUSION:
Our data show that in a large population-based cohort, WSP is associated with increased HR for cardiovascular cause of death, underlining the need for pain assessments in cardiovascular practice.
KEYWORDS:
Cohort study; Mortality ; Population-based ; Prospective ;  Widespread pain

Dietary fiber, glycemic index, glycemic load, and renal cell carcinoma risk.
Xu X, Zhu Y, Li J, Wang S.
Carcinogenesis. 2019 Mar 11. pii: bgz049. doi: 10.1093/carcin/bgz049. [Epub ahead of print]
PMID: 30859214
Abstract
Several epidemiological studies have investigated the potential association between dietary fiber, glycemic index (GI) or glycemic load (GL) and renal cell carcinoma (RCC) risk with inconsistent results. The aim of this study was to systematically evaluate this issue with a meta-analysis approach. A comprehensive literature search up to March 2018 was performed in PubMed and Web of Science databases. Summary relative risks (RRs) and 95 % confidence intervals (CIs) were estimated with a random effects model. Twelve studies were finally included in this study (eight for fiber analysis, five for GI, and five for GL). A significant positive association was observed between GI and the risk of RCC (summary RR 1.16, 95 % CI 1.02-1.32), and no significant heterogeneity was detected among studies (I2 = 22.8%, p = 0.262). A significant inverse association was found between fiber intake and the risk of RCC (summary RR 0.82, 95 % CI 0.72-0.92), and no significant heterogeneity was observed across studies (I2 = 27.6 %, p = 0.218). GL was not significantly associated with RCC risk (summary RR 1.14, 95 % CI 0.81-1.60), and significant heterogeneity was found across studies (I2 = 78.6 %, p < 0.001). In conclusion, this systematic review and meta-analysis suggests that dietary GI and fiber may be associated with the risk of RCC. Further large prospective cohort studies are still warranted to confirm our preliminary findings.
KEYWORDS:
fiber; glycemic index; glycemic load; meta-analysis; renal cell carcinoma

Association of Midlife Diet With Subsequent Risk for Dementia.
Akbaraly TN, Singh-Manoux A, Dugravot A, Brunner EJ, Kivimäki M, Sabia S.
JAMA. 2019 Mar 12;321(10):957-968. doi: 10.1001/jama.2019.1432.
PMID: 30860560
Abstract
IMPORTANCE:
Observational studies suggest that diet is linked to cognitive health. However, the duration of follow-up in many studies is not sufficient to take into account the long preclinical phase of dementia, and the evidence from interventional studies is not conclusive.
OBJECTIVE:
To examine whether midlife diet is associated with subsequent risk for dementia.
ESIGN, SETTING, AND PARTICIPANTS:
Population-based cohort study established in 1985-1988 that had dietary intake assessed in 1991-1993, 1997-1999, and 2002-2004 and follow-up for incident dementia until March 31, 2017.
EXPOSURES:
Food frequency questionnaire to derive the Alternate Healthy Eating Index (AHEI), an 11-component diet quality score (score range, 0-110), with higher scores indicating a healthier diet.
MAIN OUTCOME AND MEASURES:
Incident dementia ascertained through linkage to electronic health records.
RESULTS:
Among 8225 participants without dementia in 1991-1993 (mean age, 50.2 years [SD, 6.1 years]; 5686 [69.1%] were men), a total of 344 cases of incident dementia were recorded during a median follow-up of 24.8 years (interquartile range, 24.2-25.1 years). No significant difference in the incidence rate for dementia was observed in tertiles of AHEI exposure during 1991-1993, 1997-1999 (median follow-up, 19.1 years), and 2002-2004 (median follow-up, 13.5 years). Compared with an incidence rate for dementia of 1.76 (95% CI, 1.47-2.12) per 1000 person-years in the worst tertile of AHEI (lowest tertile of diet quality) in 1991-1993, the absolute rate difference for the intermediate tertile was 0.03 (95% CI, -0.43 to 0.49) per 1000 person-years and for the best tertile was 0.04 (95% CI, -0.42 to 0.51) per 1000 person-years. Compared with the worst AHEI tertile in 1997-1999 (incidence rate for dementia, 2.06 [95% CI, 1.62 to 2.61] per 1000 person-years), the absolute rate difference for the intermediate AHEI tertile was 0.14 (95% CI, -0.58 to 0.86) per 1000 person-years and for the best AHEI tertile was 0.14 (95% CI, -0.58 to 0.85) per 1000 person-years. Compared with the worst AHEI tertile in 2002-2004 (incidence rate for dementia, 3.12 [95% CI, 2.49 to 3.92] per 1000 person-years), the absolute rate difference for the intermediate AHEI tertile was -0.61 (95% CI, -1.56 to 0.33) per 1000 person-years and for the best AHEI tertile was -0.73 (95% CI, -1.67 to 0.22) per 1000 person-years. In the multivariable analysis, the adjusted hazard ratios (HRs) for dementia per 1-SD (10-point) AHEI increment were not significant as assessed in 1991-1993 (adjusted HR, 0.97 [95% CI, 0.87 to 1.08]), in 1997-1999 (adjusted HR, 0.97 [95% CI, 0.83 to 1.12]), or in 2002-2004 (adjusted HR, 0.87 [95% CI, 0.75 to 1.00]).
CONCLUSIONS AND RELEVANCE:
In this long-term prospective cohort study, diet quality assessed during midlife was not significantly associated with subsequent risk for dementia.

[AlPater]

Healthy dietary pattern and their corresponding gut microbiota profile are linked to a lower risk of type 2 diabetes, independent of the presence of obesity.
Díaz-Rizzolo DA, Kostov B, López-Siles M, Serra A, Colungo C, González-de-Paz L, Martinez-Medina M, Sisó-Almirall A, Gomis R.
Clin Nutr. 2019 Mar 4. pii: S0261-5614(19)30089-5. doi: 10.1016/j.clnu.2019.02.035. [Epub ahead of print]
PMID: 30876826 Free Article
https://www.clinicalnutritionjournal.com/article/S0261-5614(19)30089-5/pdf
Abstract
BACKGROUND:
Prediabetes and old age are both high risk factors for developing Type 2 Diabetes (T2D), while obesity is one of the most important factors triggering the disease. Nutritional interventions are the most effective tool for preventing T2D, as they improve different biochemical and anthropometric outcomes and growth-promoting/inhibiting gut microbiota populations. However, to date there are no specific dietary recommendations to stop the development of T2D in elderly groups, for whom hypocaloric diets and other commonly used weight-loss programs could be considered dangerous. The objective of our study, thus, was to understand the impact of dietary patterns on T2D risk as related to gut microbiota profile in obese and non-obese elderly prediabetic subjects.
METHODS:
A cross-sectional study was performed in 182 subjects ≥65 years old with prediabetes, divided into obese (OB) or non-obese (NOB) subgroups, and their risk of developing T2D was measured according to FINDRISK score and biochemical parameters. Also, clusters into different dietary patterns in each group by PCA analysis was related with gut microbiota, which was analyzed from stool samples by qPCR. The creation of clusters was used to re-evaluate T2D risk.
RESULTS:
OB was at higher risk of developing T2D and showed worse metabolic outcomes. Unhealthier and healthier dietary pattern clusters were observed for both OB (OB-6 and OB-5 respectively) and NOB (NOB-2 and NOB-3 respectively) groups. Results obtained from the gut microbiota showed that only Prevotella was higher in NOB, but when comparisons were made between clusters, a clear relation with dietary pattern was observed; showing in healthier dietary clusters a decrease in Prevotella, an increase of Faecalibacterium prausnitzii and an increase in lactic acid bacteria. T2D risk was greater in the obese group between unhealthier dietary clusters. No difference between healthier dietary clusters was observed.
CONCLUSION:
A healthy dietary pattern and the growth-promoting beneficial and growth-inhibiting disadvantageous gut microbiota populations linked to it provide protection against the development of T2D in an obese population with advanced age and preDM.
KEYWORDS:
Diabetes; Diet; Microbiota; Nutrition; Obesity; Prevention

Effects of a long-term lifestyle intervention on metabolically healthy women with obesity: Metabolite profiles according to weight loss response.
Palau-Rodriguez M, Garcia-Aloy M, Miñarro A, Bernal-Lopez MR, Brunius C, Gómez-Huelgas R, Landberg R, Tinahones FJ, Andres-Lacueva C.
Clin Nutr. 2019 Feb 16. pii: S0261-5614(19)30036-6. doi: 10.1016/j.clnu.2019.01.018. [Epub ahead of print]
PMID: 30862367
https://sci-hub.tw/10.1016/j.clnu.2019.01.018
Abstract
BACKGROUND & AIMS:
The benefits of weight loss in subjects with metabolically healthy obesity (MHO) are still a matter of controversy. We aimed to identify metabolic fingerprints and their associated pathways that discriminate women with MHO with high or low weight loss response after a lifestyle intervention, based on a hypocaloric Mediterranean diet (MedDiet) and physical activity.
METHODS:
A UPLC-Q-Exactive-MS/MS metabolomics workflow was applied to plasma samples from 27 women with MHO before and after 12 months of a hypocaloric weight loss intervention with a MedDiet and increased physical activity. The subjects were stratified into two age-matched groups according to weight loss: <10% (low weight loss group, LWL) and >10% (high weight loss group, HWL). Random forest analysis was performed to identify metabolites discriminating between the LWL and the HWL as well as within-status effects. Modulated pathways and associations between metabolites and anthropometric and biochemical variables were also investigated.
RESULTS:
Thirteen metabolites discriminated between the LWL and the HWL, including 1,5-anhydroglucitol, carotenediol, 3-(4-hydroxyphenyl)lactic acid, N-acetylaspartate and several lipid species (steroids, a plasmalogen, sphingomyelins, a bile acid and long-chain acylcarnitines). 1,5-anhydroglucitol, 3-(4-hydroxyphenyl)lactic acid and sphingomyelins were positively associated with weight variables whereas N-acetylaspartate and the plasmalogen correlated negatively with them. Changes in very long-chain acylcarnitines and hydroxyphenyllactic levels were observed in the HWL and positively correlated with fasting glucose, and changes in levels of the plasmalogen negatively correlated with insulin resistance. Additionally, the cholesterol profile was positively associated with changes in acid hydroxyphenyllactic, sphingolipids and 1,5-AG.
CONCLUSIONS:
Higher weight loss after a hypocaloric MedDiet and increased physical activity for 12 months is associated with changes in the plasma metabolome in women with MHO. These findings are associated with changes in biochemical variables and may suggest an improvement of the cardiometabolic risk profile in those patients that lose greater weight. Further studies are needed to investigate whether the response of those subjects with MHO to this intervention differs from those with unhealthy obesity.
KEYWORDS:
LC-MS; Lifestyle intervention; Mediterranean diet; Metabolically healthy obese; Metabolomics; Obesity

What my DNA told me about what I should eat
Social Sharing
Companies offer to point you toward the optimal eating and exercise habits for your genetics
Candice Choi · The Associated Press · Posted: Mar 26, 2019 
https://www.cbc.ca/news/health/dna-test-medical-1.5072389

Weight Training and Risk of 10 Common Types of Cancer.
Mazzilli KM, Matthews CE, Salerno EA, Moore SC.
Med Sci Sports Exerc. 2019 Mar 25. doi: 10.1249/MSS.0000000000001987. [Epub ahead of print]
PMID: 30920488
Abstract
INTRODUCTION:
Ample data support that leisure time aerobic moderate to vigorous physical activity (MVPA) is associated with lower risk of at least seven types of cancer. However, the link between muscle-strengthening activities and cancer etiology is not well-understood. Our objective was to determine the association of weight lifting with incidence of 10 common cancer types.
METHODS:
We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for association of weight lifting with incidence of 10 cancer types in the NIH-AARP Diet and Health Study follow-up. Weight lifting was modeled continuously and categorically. Dose-response relationships were evaluated using cubic restricted spline models. We explored whether associations varied by subgroups defined by sex, age, and body mass index (BMI) using the Wald test for homogeneity. We examined joint categories of MVPA and weight lifting in relation to cancer risk for significant associations.
RESULTS:
After adjusting for all covariates including MVPA, we observed a statistically significant lower risk of colon cancer (Ptrend=0.003) in individuals who weight lifted; the HR and 95% CI associated with low and high weight lifting as compared with no weight lifting were 0.75(CI:0.66,0.87) and 0.78(CI:0.61,0.98) respectively. This relationship differed between men and women (HRmen=0.91 ;CI:0.84, 0.98; HRwomen=1.00; CI:0.93, 1.08) (Pinteraction=0.008). A lower risk of kidney cancer among weight lifters was observed but became non-significant after adjusting for MVPA (Ptrend=0.06); resulting in a HR of 0.94 (CI:0.78,1.12) for low weight lifting and 0.80 (CI:0.59,1.11) for high weight lifting.
CONCLUSION:
Participants who engaged in weight lifting had a significantly lower risk of colon cancer and a trend towards a lower risk of kidney cancer than participants who did not weight lift. KeywordsResistance, strengthening, epidemiology, physical activity, colon.

Coffee consumption and colorectal cancer risk: a dose-response meta-analysis on prospective cohort studies.
Micek A, Gniadek A, Kawalec P, Brzostek T.
Int J Food Sci Nutr. 2019 Mar 28:1-21. doi: 10.1080/09637486.2019.1591352. [Epub ahead of print]
PMID: 30922134
https://sci-hub.tw/https://www.tandfonline.com/doi/full/10.1080/09637486.2019.1591352
Abstract
Evidence regarding the influence of coffee drinking on colorectal cancer (CRC) is limited, and it remains unclear whether coffee consumption is associated with the risk of the disease. To clarify this association, a comprehensive meta-analysis was performed. The risk of CRC was compared between the categories of coffee consumption, and a dose-response relationship was studied using restricted cubic splines. We did not find evidence for the association between coffee consumption and CRC risk. Among alternative study inclusions, when using pooled projects, coffee consumption was related with a decreased risk of colon cancer in a subgroup analysis of never-smokers and in Asian countries, and with an increased risk of rectal cancer in an analysis of the general population and after restriction to women, never-smokers, and European countries. In conclusion, the association between coffee consumption and CRC risk is controversial and should be clarified in further cohort studies.
KEYWORDS:
Coffee; cancer; colon; colorectal; meta-analysis; rectal

Adipokines and Aging: Findings From Centenarians and the Very Old.
Arai Y, Kamide K, Hirose N.
Front Endocrinol (Lausanne). 2019 Mar 14;10:142. doi: 10.3389/fendo.2019.00142. eCollection 2019. Review.
PMID: 30923512
[pdf free from https://www.ncbi.nlm.nih.gov/pubmed/30923512 site.]
Abstract
Adipose tissue, which was once considered as a simple energy storage depot, is now recognized as an active endocrine organ that regulates the whole-body energy homeostasis by secreting hundreds of bioactive substances termed adipokines. Dysregulation of adipokines is a key feature of insulin resistance and a metabolic syndrome associated with obesity. Adipokine dysregulation and insulin resistance are also associated with energy-deprivation conditions, such as frailty in old age. Previous studies have demonstrated that preserved insulin sensitivity and low prevalence of diabetes are the metabolic peculiarities of centenarians, suggesting the possible role of adipokine homeostasis in healthy longevity. Among the numerous adipokines, adiponectin is regarded as unique and salutary, showing negative correlations with several age- and obesity-related metabolic disturbances and a positive correlation with longevity and insulin sensitivity among centenarians. However, large-scale epidemiological studies have implied the opposite aspect of this adipokine as a prognostic factor for all-cause and cardiovascular mortality in patients with heart failure or kidney disease. In this review, the clinical significance of adiponectin was comparatively addressed in centenarians and the very old, in terms of frailty, cardiovascular risk, and mortality.
KEYWORDS:
adipokines; adiponectin; centenarian; frailty; longevity

[AlPater]

Glycine supplementation extends lifespan of male and female mice.
Miller RA, Harrison DE, Astle CM, Bogue MA, Brind J, Fernandez E, Flurkey K, Javors M, Ladiges W, Leeuwenburgh C, Macchiarini F, Nelson J, Ryazanov AG, Snyder J, Stearns TM, Vaughan DE, Strong R.
Aging Cell. 2019 Mar 27:e12953. doi: 10.1111/acel.12953. [Epub ahead of print]
PMID: 30916479 Free Article
https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.12953
Abstract
Diets low in methionine extend lifespan of rodents, though through unknown mechanisms. Glycine can mitigate methionine toxicity, and a small prior study has suggested that supplemental glycine could extend lifespan of Fischer 344 rats. We therefore evaluated the effects of an 8% glycine diet on lifespan and pathology of genetically heterogeneous mice in the context of the Interventions Testing Program. Elevated glycine led to a small (4%-6%) but statistically significant lifespan increase, as well as an increase in maximum lifespan, in both males (p = 0.002) and females (p < 0.001). Pooling across sex, glycine increased lifespan at each of the three independent sites, with significance at p = 0.01, 0.053, and 0.03, respectively. Glycine-supplemented females were lighter than controls, but there was no effect on weight in males. End-of-life necropsies suggested that glycine-treated mice were less likely than controls to die of pulmonary adenocarcinoma (p = 0.03). Of the 40 varieties of incidental pathology evaluated in these mice, none were increased to a significant degree by the glycine-supplemented diet. In parallel analyses of the same cohort, we found no benefits from TM5441 (an inhibitor of PAI-1, the primary inhibitor of tissue and urokinase plasminogen activators), inulin (a source of soluble fiber), or aspirin at either of two doses. Our glycine results strengthen the idea that modulation of dietary amino acid levels can increase healthy lifespan in mice, and provide a foundation for further investigation of dietary effects on aging and late-life diseases.
KEYWORDS:
anti-aging; life span; longevity regulation

The Influence of Meal Frequency and Timing on Health in Humans: The Role of Fasting.
Paoli A, Tinsley G, Bianco A, Moro T.
Nutrients. 2019 Mar 28;11(4). pii: E719. doi: 10.3390/nu11040719. Review.
PMID: 30925707
https://www.mdpi.com/2072-6643/11/4/719/htm
Abstract
The influence of meal frequency and timing on health and disease has been a topic of interest for many years. While epidemiological evidence indicates an association between higher meal frequencies and lower disease risk, experimental trials have shown conflicting results. Furthermore, recent prospective research has demonstrated a significant increase in disease risk with a high meal frequency (≥6 meals/day) as compared to a low meal frequency (1⁻2 meals/day). Apart from meal frequency and timing we also have to consider breakfast consumption and the distribution of daily energy intake, caloric restriction, and night-time eating. A central role in this complex scenario is played by the fasting period length between two meals. The physiological underpinning of these interconnected variables may be through internal circadian clocks, and food consumption that is asynchronous with natural circadian rhythms may exert adverse health effects and increase disease risk. Additionally, alterations in meal frequency and meal timing have the potential to influence energy and macronutrient intake.A regular meal pattern including breakfast consumption, consuming a higher proportion of energy early in the day, reduced meal frequency (i.e., 2⁻3 meals/day), and regular fasting periods may provide physiological benefits such as reduced inflammation, improved circadian rhythmicity, increased autophagy and stress resistance, and modulation of the gut microbiota.
KEYWORDS:
cardiovascular health; diabetes; fasting; meal frequency; meal timing; obesity; time-restricted feeding

Urinary ionomic analysis reveals new relationship between minerals and longevity in a Han Chinese population.
Li Q, Hu C, Lin J, Yang Z, Zhou Q, Yang R, Yuan H, Zhu X, Lv Y, Liang Q, Lv Z, Sun L, Zhang Y.
J Trace Elem Med Biol. 2019 May;53:69-75. doi: 10.1016/j.jtemb.2019.02.002. Epub 2019 Feb 12.
PMID: 30910209
https://sci-hub.tw/10.1016/j.jtemb.2019.02.002
Abstract
Human longevity involves genetic, nutritional, environmental and many other factors playing a key role in healthy aging. Previous studies have shown that mineral metabolism and homeostasis are associated with lifespan extension. However, the majority of them have focused on a limited number of elements and ignored the complex relationship between them. In this study, we carried out a network-based approach to investigate the urinary ionome of nonagenarians and centenarians (longevity group) when compared with their biologically unrelated and younger family members (control group) from a Han Chinese population. Several differentially changed elements were identified, almost all of which showed an elevated level in the longevity group. Correlation analysis of the ionome revealed significant element-element interactions in each group. We then divided each group into distinct subgroups according to age ranges, and built the elemental correlation network for each of them. Significant elemental correlations and correlation changes involving all examined elements were identified within or between different subgroups, implying a highly dynamic and complex crosstalk among the elements during human life. Finally, more similar elemental patterns were observed between extremely old and middle-aged people. Overall, our data reveal new relationship between urinary minerals and human longevity, which may extend our understanding of the mechanism of healthy aging.
KEYWORDS:
Aging; Correlation network; Ionome; Longevity; Metal

Joint association of urinary sodium and potassium excretion with cardiovascular events and mortality: prospective cohort study.
O'Donnell M, Mente A, Rangarajan S, McQueen MJ, O'Leary N, Yin L, Liu X, Swaminathan S, Khatib R, Rosengren A, Ferguson J, Smyth A, Lopez-Jaramillo P, Diaz R, Avezum A, Lanas F, Ismail N, Yusoff K, Dans A, Iqbal R, Szuba A, Mohammadifard N, Oguz A, Yusufali AH, Alhabib KF, Kruger IM, Yusuf R, Chifamba J, Yeates K, Dagenais G, Wielgosz A, Lear SA, Teo K, Yusuf S; PURE Investigators.
BMJ. 2019 Mar 13;364:l772. doi: 10.1136/bmj.l772.
PMID: 30867146 Free Article
https://www.bmj.com/content/bmj/364/bmj.l772.full.pdf
Abstract
OBJECTIVE:
To evaluate the joint association of sodium and potassium urinary excretion (as surrogate measures of intake) with cardiovascular events and mortality, in the context of current World Health Organization recommendations for daily intake (<2.0 g sodium, >3.5 g potassium) in adults.
DESIGN:
International prospective cohort study.
SETTING:
18 high, middle, and low income countries, sampled from urban and rural communities.
PARTICIPANTS:
103 570 people who provided morning fasting urine samples.
MAIN OUTCOME MEASURES:
Association of estimated 24 hour urinary sodium and potassium excretion (surrogates for intake) with all cause mortality and major cardiovascular events, using multivariable Cox regression. A six category variable for joint sodium and potassium was generated: sodium excretion (low (<3 g/day), moderate (3-5 g/day), and high (>5 g/day) sodium intakes) by potassium excretion (greater/equal or less than median 2.1 g/day).
RESULTS:
Mean estimated sodium and potassium urinary excretion were 4.93 g/day and 2.12 g/day, respectively. After a median follow-up of 8.2 years, 7884 (6.1%) participants had died or experienced a major cardiovascular event. Increasing urinary sodium excretion was positively associated with increasing potassium excretion (unadjusted r=0.34), and only 0.002% had a concomitant urinary excretion of <2.0 g/day of sodium and >3.5 g/day of potassium. A J-shaped association was observed of sodium excretion and inverse association of potassium excretion with death and cardiovascular events. For joint sodium and potassium excretion categories, the lowest risk of death and cardiovascular events occurred in the group with moderate sodium excretion (3-5 g/day) and higher potassium excretion (21.9% of cohort). Compared with this reference group, the combinations of low potassium with low sodium excretion (hazard ratio 1.23, 1.11 to 1.37; 7.4% of cohort) and low potassium with high sodium excretion (1.21, 1.11 to 1.32; 13.8% of cohort) were associated with the highest risk, followed by low sodium excretion (1.19, 1.02 to 1.38; 3.3% of cohort) and high sodium excretion (1.10, 1.02 to 1.18; 29.6% of cohort) among those with potassium excretion greater than the median. Higher potassium excretion attenuated the increased cardiovascular risk associated with high sodium excretion (P for interaction=0.007).
CONCLUSIONS:
These findings suggest that the simultaneous target of low sodium intake (<2 g/day) with high potassium intake (>3.5 g/day) is extremely uncommon. Combined moderate sodium intake (3-5 g/day) with high potassium intake is associated with the lowest risk of mortality and cardiovascular events.

Influence of rapid eye movement sleep on all-cause mortality: a community-based cohort study.
Zhang J, Jin X, Li R, Gao Y, Li J, Wang G.
Aging (Albany NY). 2019 Mar 13;11(5):1580-1588. doi: 10.18632/aging.101858.
PMID: 30867337 Free PMC Article
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428105/pdf/aging-11-101858.pdf
Abstract
INTRODUCTION:
Although the proportion and duration of rapid eye movement (REM) sleep are correlated with neurological and cardiovascular diseases, whether REM sleep is associated with all-cause mortality in community-based populations remains unknown.
METHODS:
A prospective study was performed within the Sleep Heart Health Study (SHHS, Registration NO. NCT00005275). Total sleep time, sleep efficiency, and REM sleep were measured using polysomnography. Cox proportional hazards regression models were used to estimate the association of the REM sleep with all-cause mortality.
RESULTS:
Over a mean follow-up period of 11.0 ± 3.1 y, 1234 individuals (21.9%) died. In the entire population, reduced REM sleep was significantly associated with increasing all-cause mortality. After adjustment for age, sex, race, body mass index, smoking status, total cholesterol, triglycerides, high-density lipoprotein, history of diabetes and hypertension, and the apnea-hypopnea index, the duration and proportion of REM sleep were found to be significantly associated with all-cause mortality when the lowest and the highest REM quartile groups were compared (hazard ratio, 95% confidence interval: 1.727, 1.434-2.079; 1.545, 1.298-1.839; respectively).
CONCLUSION:
The proportion and duration of REM sleep are negatively associated with all-cause mortality. This finding emphasizes the importance of personalized sleep management in community-based populations.
KEYWORDS:
all-cause mortality; community; polysomnography; rapid eye movement sleep

High-density Lipoprotein Cholesterol and All-cause and Cause-specific Mortality Among the Elderly.
Li ZH, Lv YB, Zhong WF, Gao X, Kraus VB, Zou MC, Zhang XR, Li FR, Yuan JQ, Shi XM, Wu XB, Mao C.
J Clin Endocrinol Metab. 2019 Mar 14. pii: jc.2018-02511. doi: 10.1210/jc.2018-02511. [Epub ahead of print]
PMID: 30869791
Abstract
CONTEXT:
The patterns of the association between high-density lipoprotein cholesterol (HDL-C) concentrations and mortality among the elderly are still unclear.
OBJECTIVE:
To examine the association of HDL-C concentrations with mortality, and to identify the optimal HDL-C concentration range that predicts the lowest risk of all-cause mortality among the elderly.
DESIGN:
This was a nationwide, community-based prospective cohort study.
METHODS:
This study included 7,766 elderly individuals (aged ≥65 years; mean age: 74.4 years) from the Health and Retirement Study. Cox proportional hazards models and Cox models with penalized smoothing splines were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause and cause-specific mortality.
RESULTS:
During a median follow-up of 5.9 years, 1,921 deaths occurred. After fully adjustment for covariates, a nonlinear (P for nonlinearity<0.001) association was found between HDL-C and all-cause mortality (minimum mortality risk at 71 mg/dL [1.84 mM]); the risk for all-cause mortality was significantly higher in the group with HDL-C concentration <61 mg/dL (1.58 mM) (HR: 1.18; 95% CI: 1.05-1.33) and in the group with HDL-C concentration >87 mg/dL (2.25 mM) (HR: 1.56; 95% CI: 1.17-2.07) than in the group with HDL-C concentrations ranging from 61 to 87 mg/dL (1.58-2.25 mM). Nonlinear associations of HDL-C concentrations with both cardiovascular and non-cardiovascular mortality were also observed (both P for nonlinearity<0.001).
CONCLUSIONS:
Among the elderly, nonlinear associations were found between HDL-C and all-cause and cardiovascular mortality. The single optimal HDL-C concentration and range were 71 mg/dL and 61 to 87 mg/dL, respectively.

Associations of Dietary Cholesterol or Egg Consumption With Incident Cardiovascular Disease and Mortality.
Zhong VW, Van Horn L, Cornelis MC, Wilkins JT, Ning H, Carnethon MR, Greenland P, Mentz RJ, Tucker KL, Zhao L, Norwood AF, Lloyd-Jones DM, Allen NB.
JAMA. 2019 Mar 19;321(11):1081-1095. doi: 10.1001/jama.2019.1572.
PMID: 30874756
Abstract
IMPORTANCE:
Cholesterol is a common nutrient in the human diet and eggs are a major source of dietary cholesterol. Whether dietary cholesterol or egg consumption is associated with cardiovascular disease (CVD) and mortality remains controversial.
OBJECTIVE:
To determine the associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality.
DESIGN, SETTING, AND PARTICIPANTS:
Individual participant data were pooled from 6 prospective US cohorts using data collected between March 25, 1985, and August 31, 2016. Self-reported diet data were harmonized using a standardized protocol.
EXPOSURES:
Dietary cholesterol (mg/day) or egg consumption (number/day).
MAIN OUTCOMES AND MEASURES:
Hazard ratio (HR) and absolute risk difference (ARD) over the entire follow-up for incident CVD (composite of fatal and nonfatal coronary heart disease, stroke, heart failure, and other CVD deaths) and all-cause mortality, adjusting for demographic, socioeconomic, and behavioral factors.
RESULTS:
This analysis included 29 615 participants (mean [SD] age, 51.6 [13.5] years at baseline) of whom 13 299 (44.9%) were men and 9204 (31.1%) were black. During a median follow-up of 17.5 years (interquartile range, 13.0-21.7; maximum, 31.3), there were 5400 incident CVD events and 6132 all-cause deaths. The associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality were monotonic (all P values for nonlinear terms, .19-.83). Each additional 300 mg of dietary cholesterol consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.17 [95% CI, 1.09-1.26]; adjusted ARD, 3.24% [95% CI, 1.39%-5.08%]) and all-cause mortality (adjusted HR, 1.18 [95% CI, 1.10-1.26]; adjusted ARD, 4.43% [95% CI, 2.51%-6.36%]). Each additional half an egg consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.06 [95% CI, 1.03-1.10]; adjusted ARD, 1.11% [95% CI, 0.32%-1.89%]) and all-cause mortality (adjusted HR, 1.08 [95% CI, 1.04-1.11]; adjusted ARD, 1.93% [95% CI, 1.10%-2.76%]). The associations between egg consumption and incident CVD (adjusted HR, 0.99 [95% CI, 0.93-1.05]; adjusted ARD, -0.47% [95% CI, -1.83% to 0.88%]) and all-cause mortality (adjusted HR, 1.03 [95% CI, 0.97-1.09]; adjusted ARD, 0.71% [95% CI, -0.85% to 2.28%]) were no longer significant after adjusting for dietary cholesterol consumption.
CONCLUSIONS AND RELEVANCE:
Among US adults, higher consumption of dietary cholesterol or eggs was significantly associated with higher risk of incident CVD and all-cause mortality in a dose-response manner. These results should be considered in the development of dietary guidelines and updates.
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Reconsidering the Importance of the Association of Egg Consumption and Dietary Cholesterol With Cardiovascular Disease Risk.
Eckel RH.
JAMA. 2019 Mar 19;321(11):1055-1056. doi: 10.1001/jama.2019.1850. No abstract available.
PMID: 30874737
https://sci-hub.tw/10.1001/jama.2019.1850

Association of Weight Fluctuation With Mortality in Japanese Adults.
Cologne J, Takahashi I, French B, Nanri A, Misumi M, Sadakane A, Cullings HM, Araki Y, Mizoue T.
JAMA Netw Open. 2019 Mar 1;2(3):e190731. doi: 10.1001/jamanetworkopen.2019.0731.
PMID: 30874785
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2728007
Abstract
IMPORTANCE:
Weight cycling is associated with the risk of mortality from heart disease, but many studies have not distinguished between simple nonlinear (monotone) weight changes and more complex changes that reflect fluctuations.
OBJECTIVE:
To assess whether extreme body weight variation is associated with mortality after controlling for nonlinear weight changes.
DESIGN, SETTING, AND PARTICIPANTS:
In this prospective clinical cohort study, 4796 Japanese atomic bomb survivors were examined in the clinic as part of a biennial health examination and research program. The study consisted of a 20-year longitudinal baseline period (July 1, 1958, to June 30, 1978) and subsequent mortality follow-up of 27 years (July 1, 1978, to June 30, 2005) Participants were initially between the ages of 20 and 49 years during the baseline period and, throughout the baseline period, had no diagnoses of cardiovascular disease (CVD) or cancer and attended at least 7 of 10 scheduled examinations. Data analysis was performed from October 16, 2015, to May 13, 2016.
EXPOSURES:
Residual variability in body mass index (BMI) during the baseline period.
MAIN OUTCOMES AND MEASURES:
Outcomes were mortality from ischemic heart disease, cerebrovascular disease, other CVDs combined, other causes (except cancer), and cancer. Root mean squared error was calculated to capture individual residual variation in BMI after adjustment for baseline BMI trends, and the association of magnitude of residual variation with mortality was calculated as relative risk.
RESULTS:
In total, 4796 persons (mean [SD] age, 35.0 [7.3] years at first baseline examination; 3252 [67.8%] female; mean [SD] BMI, 21.2 [2.8] at first baseline visit [20.6 (2.4) among men and 21.5 (2.9) among women]) participated in the study. During follow-up, 1550 participants died: 82 (5.3% of all deaths) of ischemic heart disease, 181 (11.7%) of cerebrovascular disease, 186 (12.0%) of other CVDs, 615 (39.7%) of cancer, and 486 (31.3%) of other causes. Magnitude of residual variation in weight was associated with all-cause mortality (relative risk, 1.25 for 1 U of additional variation; 95% CI, 1.06-1.47) and ischemic heart disease mortality (relative risk, 2.49; 95% CI, 1.41-4.38).
CONCLUSIONS AND RELEVANCE:
The findings suggest that an association exists between weight variation and heart disease mortality and that weight loss interventions, if deemed to be necessary, should be considered carefully.

[AlPater]

All-cause mortality and long-term exposure to low level air pollution in the '45 and up study' cohort, Sydney, Australia, 2006-2015.
Hanigan IC, Rolfe MI, Knibbs LD, Salimi F, Cowie CT, Heyworth J, Marks GB, Guo Y, Cope M, Bauman A, Jalaludin B, Morgan GG.
Environ Int. 2019 May;126:762-770. doi: 10.1016/j.envint.2019.02.044. Epub 2019 Mar 15.
PMID: 30878871 Free Article
Abstract
BACKGROUND:
Epidemiological studies show that long-term exposure to ambient air pollution reduces life expectancy. Most studies have been in environments with relatively high concentrations such as North America, Europe and Asia. Associations at the lower end of the concentration-response function are not well defined.
OBJECTIVES:
We assessed associations between all-cause mortality and exposure to annual average particulate matter <2.5 μm (PM2.5) and nitrogen dioxide (NO2) in Sydney, Australia, where concentrations are relatively low.
METHODS:
The '45 and Up Study' comprises a prospective longitudinal cohort from the state of New South Wales, Australia with 266,969 participants linked to death registry data. We analyzed data for the participants who resided in Sydney at baseline questionnaire (n = 75,268). Exposures to long-term pollution were estimated using annual averages from a chemical transport model (PM2.5), and a satellite-based land-use regression model (NO2). Socio-demographic information was extracted from the baseline questionnaire. Cox proportional hazard models were applied to estimate associations, while adjusting for covariates.
RESULTS:
In our cohort mean annual PM2.5 was 4.5 μg/m3 and mean NO2 was 17.8 μg/m3. The mortality rate was 4.4% over the 7 years of follow up. Models that adjusted for individual-level and area-level risk factors resulted in a detrimental non statistically significant hazard ratio (HR) of 1.05 (95% CI: 0.98-1.12) per 1 μg/m3 increase in PM2.5, and 1.03 (95% CI: 0.98-1.07) per 5 μg/m3 increase in NO2.
CONCLUSIONS:
We found evidence that low-level air pollution exposure was associated with increased risk of mortality in this cohort of adults aged 45 years and over, even at the relatively low concentrations seen in Sydney. However, a clear determination of the association with mortality is difficult because the results were sensitive to some covariates. Our findings are supportive of emerging evidence that exposure to low levels of air pollution reduces life expectancy.
KEYWORDS:
All-cause mortality; Fine particulate matter; Gaseous pollutants; Low concentration; Survival model

Glycated Hemoglobin and All-cause and Cause-specific Mortality Among Adults With and Without Diabetes.
Li FR, Zhang XR, Zhong WF, Li ZH, Gao X, Kraus VB, Lv YB, Zou MC, Chen GC, Chen PL, Zhang MY, Kur AKA, Shi XM, Wu XB, Mao C.
J Clin Endocrinol Metab. 2019 Mar 21. pii: jc.2018-02536. doi: 10.1210/jc.2018-02536. [Epub ahead of print]
PMID: 30896760
Abstract
CONTEXT:
The patterns of associations between glycated hemoglobin (HbA1c) and mortality are still unclear.
OBJECTIVE:
To explore the extent to which ranges of HbA1c levels are associated with the risk of mortality among participants with and without diabetes.
DESIGN:
Setting and patients: This was a nationwide, community-based prospective cohort study. Included were 15,869 participants (median age 64 years) of the Health and Retirement Study, with available HbA1c data and without a history of cancer. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidential intervals (95% CIs) for mortality.
RESULTS:
A total of 2,133 participants died during a median follow-up of 5.8 years. In participants with diabetes, those with an HbA1c level of 6.5% were at the lowest risk of all-cause mortality. When HbA1c level was lower than 5.6% or higher than 7.4%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 6.5%. As for participants without diabetes, those with an HbA1c level of 5.4% were at the lowest risk of all-cause mortality. When HbA1c level was lower than 5.0%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 5.4%. However, we did not observe a statistically significant elevated risk of all-cause mortality above an HbA1c level of 5.4%.
CONCLUSIONS:
A U-shaped and a reverse J-shaped association for all-cause mortality were found among participants with and without diabetes. The corresponding Optimal ranges for overall survival are predicted to be 5.6-7.4% and 5.0-6.5%, respectively.

Socioeconomic trajectories across the life course and risk of total and cause-specific mortality: prospective findings from the Moli-sani Study.
Bonaccio M, Di Castelnuovo A, Costanzo S, De Curtis A, Persichillo M, Cerletti C, Donati MB, de Gaetano G, Iacoviello L; Moli-sani Study investigators.
J Epidemiol Community Health. 2019 Mar 21. pii: jech-2018-211582. doi: 10.1136/jech-2018-211582. [Epub ahead of print]
PMID: 30898851
https://sci-hub.tw/https://jech.bmj.com/content/early/2019/03/08/jech-2018-211582
Abstract
BACKGROUND:
A life course approach has been suggested as the most appropriate to establish the total impact of socioeconomic status (SES) on adult health outcomes; however, such an approach has been poorly used within Mediterranean populations. We aimed to examine the SES trajectories from childhood to adulthood associated with mortality risk in a large general population-based cohort and to test potential pathways (eg, inflammation) underlying such associations.
METHODS:
Longitudinal analyses on 22 194 subjects recruited in the Moli-sani Study, Italy (2005-2010). Low and high SES in childhood, educational attainment (low/high) and SES during adulthood (measured by a score including material resources and dichotomised as low/high) were used to define overall trajectories.
RESULTS:
Over 8.3 years of follow-up, 1155 deaths occurred. In the group with poor childhood SES, an upward trajectory in both educational and material circumstances was associated with lower risk of all-cause death (HR=0.64; 95% CI 0.47 to 0.87), as opposed to subjects who remained stably low (low education and adulthood SES). Subjects with high childhood SES, but not educational achievement, were at increased risk of total and cardiovascular disease (CVD) death, although reporting higher material SES in adult life, as compared with the stably high SES group (HR=1.44; 1.02 to 2.02 and HR=1.90; 1.10 to 3.28, respectively). Inflammatory markers marginally accounted for such associations.
CONCLUSION:
For individuals with low SES in early life, an educational and material upward trajectory over the life course was associated with lower mortality risk. In the high SES childhood group, lack of a higher educational attainment appeared to be unfavourably associated with survival.
KEYWORDS:
cumulative socioeconomic disadvantage; inflammation; life course; mortality; socioeconomic status; socioeconomic trajectories

Marital status and 5-year mortality: A population-based prospective cohort study.
Lindström M, Rosvall M.
Public Health. 2019 Mar 28;170:45-48. doi: 10.1016/j.puhe.2019.02.015. [Epub ahead of print]
PMID: 30928612 Free Article
https://reader.elsevier.com/reader/sd/pii/S0033350619300514?token=923B4F385E7D45D6C0A0717B72FABDF708469DE37C1E0277DBFECCF43DBF3C203742DA9A6AD93532E6D3D0B179606811
Abstract
OBJECTIVES:
The aim was to investigate the association between baseline marital status and mortality using survival (Cox-regression) analysis.
STUDY DESIGN:
This is a prospective cohort study.
METHODS:
The public health survey by Scania in 2008 was linked to the Swedish cause of death register. This prospective cohort study includes 12,245 men and 14,969 women aged 18-80 years, and 538 men and 362 women of them died during the 5.3-year follow-up.
RESULTS:
Unmarried, divorced, and widowed men had significantly higher hazard rate ratios (HRRs) of all-cause mortality than married/cohabitating men. For women, the HRRs of these groups did not significantly differ from those of the married/cohabitating reference group.
CONCLUSIONS:
The results are in accordance with a previous study that only compared those living alone with those cohabitating.
KEYWORDS:
Marital status; Mortality; Partnership; Prospective cohort study; Sweden

[AlPater]

Specific Leisure Activities and Cognitive Functions Among the Oldest-Old: the Chinese Longitudinal Healthy Longevity Survey.
Mao C, Li ZH, Lv YB, Gao X, Kraus VB, Zhou JH, Wu XB, Shi WY, Li FR, Liu SM, Yin ZX, Zeng Y, Shi XM.
J Gerontol A Biol Sci Med Sci. 2019 Apr 4. pii: glz086. doi: 10.1093/gerona/glz086. [Epub ahead of print]
PMID: 30946444
Abstract
Little is known about the role of specific leisure activities in affecting cognitive functions. We aim to examine the associations of specific leisure activities with the risk of cognitive impairment among oldest-old people in China. This community-based prospective cohort study included 10,741 cognitively normal Chinese individuals aged 80 years or older (median age 88 years) from the Chinese Longitudinal Healthy Longevity Survey. Cognitive function was assessed using the Mini-mental State Examination (MMSE). Cox proportional hazards models were utilized to estimate the effects of specific leisure activities on cognitive impairment outcome. During a median follow-up time of 3.4 years (41,760 person-years), 2,894 participants developed cognitive impairment. Compared to those who 'never' engaged in watching TV or listening to radio, reading books or newspapers, and playing cards or mah-jong, those who engaged in such activities 'almost every day' reduced their risk of cognitive impairment, the fully adjusted HRs were 0.56 (0.51-0.61), 0.64 (0.53-0.78), and 0.70 (0.56-0.86), respectively. The association between the risk of cognitive impairment and watching TV and listening to the radio, playing cards or mah-jong, and reading books or newspapers were stronger among those who had 2 or more years of education. Moreover, the association between risk of cognitive impairment and watching TV and listening to radio was stronger in men than in women. In conclusion, a greater frequency of TV watching or radio listening, reading books or newspapers and playing cards or mah-jong may decrease the risk of cognitive impairment among the oldest-old.
KEYWORDS:
cognitive impairment; cohort study; leisure activity; oldest-old

The diets cutting one in five lives short every year
By James Gallagher
Health and science correspondent, BBC News
4 April 2019
https://www.bbc.com/news/health-47734296
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Health effects of dietary risks in 195 countries, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017
GBD 2017 Diet Collaborators
Lancet Open Access Published:April 03, 2019DOI:https://doi.org/10.1016/S0140-6736(19)30041-8
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)30041-8/fulltext
Summary
Background
Suboptimal diet is an important preventable risk factor for non-communicable diseases (NCDs); however, its impact on the burden of NCDs has not been systematically evaluated. This study aimed to evaluate the consumption of major foods and nutrients across 195 countries and to quantify the impact of their suboptimal intake on NCD mortality and morbidity.
Methods
By use of a comparative risk assessment approach, we estimated the proportion of disease-specific burden attributable to each dietary risk factor (also referred to as population attributable fraction) among adults aged 25 years or older. The main inputs to this analysis included the intake of each dietary factor, the effect size of the dietary factor on disease endpoint, and the level of intake associated with the lowest risk of mortality. Then, by use of disease-specific population attributable fractions, mortality, and disability-adjusted life-years (DALYs), we calculated the number of deaths and DALYs attributable to diet for each disease outcome.
Findings
In 2017, 11 million (95% uncertainty interval [UI] 10–12) deaths and 255 million (234–274) DALYs were attributable to dietary risk factors. High intake of sodium (3 million [1–5] deaths and 70 million [34–118] DALYs), low intake of whole grains (3 million [2–4] deaths and 82 million [59–109] DALYs), and low intake of fruits (2 million [1–4] deaths and 65 million [41–92] DALYs) were the leading dietary risk factors for deaths and DALYs globally and in many countries. Dietary data were from mixed sources and were not available for all countries, increasing the statistical uncertainty of our estimates.
Interpretation
This study provides a comprehensive picture of the potential impact of suboptimal diet on NCD mortality and morbidity, highlighting the need for improving diet across nations. Our findings will inform implementation of evidence-based dietary interventions and provide a platform for evaluation of their impact on human health annually.

Comparison of radical prostatectomy versus conservative treatment in localized prostate cancer: systematic review and meta-analysis.
Tian Z, Wang X, Wu P, Shi T, Liu M.
J BUON. 2019 Jan-Feb;24(1):239-248.
PMID: 30941976
Abstract
PURPOSE:
To evaluate the effects of radical prostatectomy (RP) and conservative treatment (CT) on the survival of localized prostate cancer by conducting a systematic review and meta-analysis.
METHODS:
We searched for all studies about RP and CT for localized prostate cancer in PubMed and Web of Science up to December 2017. A systematic review and meta-analysis was performed.
RESULTS:
There were 4 randomized clinical trials (RCTs) and 12 cohort studies including 69871 patients treated with RP and 65765 patients treated with CT. There was a significantly reduced all-cause mortality (HR:0.575;95%CI:0.487 to 0.678;p<0.001) along with a reduced risk of prostate cancer mortality in patients treated with RP compared to those treated with CT (HR:0.408;95%CI:0.313 to 0.533;p<0.001). RP was effective with a lower all-cause mortality and prostate cancer mortality for patients with intermediate risk disease (HR:0.774;95%CI:0.664 to 0.902,p=0.001; HR:0.428;95%CI:0.286 to 0.641, p=0.001, respectively). However, for low risk (HR:0.774;95%CI:0.505 to 1.187, p=0.241; HR:0.603;95%CI:0.332 to 1.097, p=0.098, respectively) and high risk (HR:0.662;95%CI:0.376 to 1.164, p=0.152; HR:0.584;95%CI:0.315 to 1.084, p=0.089, respectively) prostate cancer patients, there was no significant difference between RP and CT. In the subgroup analysis according to the age and follow-up time, the results favored the RP and there was no specific factor affecting the outcomes.
CONCLUSIONS:
RP offers a better survival rate than CT in patients with localized prostate cancer. For some patients with localized prostate cancer, treatment should be chosen very carefully.

[AlPater]

Plasma 25-Hydroxyvitamin D Concentrations Are Inversely Associated with All-Cause Mortality among a Prospective Cohort of Chinese Adults Aged ≥80 Years.
Mao C, Li FR, Yin ZX, Lv YB, Luo JS, Yuan JQ, Mhungu F, Wang JN, Shi WY, Zhou JH, Chen GC, Gao X, Kraus VB, Wu XB, Shi XM.
J Nutr. 2019 Apr 5. pii: nxz041. doi: 10.1093/jn/nxz041. [Epub ahead of print]
PMID: 30949685
https://watermark.silverchair.com/nxz041.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAkowggJGBgkqhkiG9w0BBwagggI3MIICMwIBADCCAiwGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMbzqxMg4e9I2NWpUKAgEQgIIB_YLB0bCqrUztSs1dnrq-1pblPEm1JdDTnSL6oVqPfKfCyNYiMo5aNWtp0a-fDI7Psa1anio6--WtAT9YS7qs4j-FsGAPP9-wDXh1hvAXulgwYksZrTawOp6cZ7gx1h3MhiGNHa03jWvnRAgrqXD_oGsIfwAZJrhmG_7AZJLJX9YZt36-1ghIcpRL6lIcX2pYnfqx1NQ2CC56kp6_8HQ9UgiuFrPncvZdQbfaD47j2b8KP4WGLjlfZhzY2fhc00GMkbTnnA8WreUowJRb1W5fuP7Ptq1aCY2R9UuEN2szDZii8vesM9-II41hcbx-rJxmsy6tmwkl9WRBrSTvuEU7AiPZJruSBia07LIOaslNsibMeIs01wRdO0ukFObx9eHRp3xEI_KId9sCDCNGFHjAf6kNVAftKCMYYG7iizQdomsE3AW-DrnQTNf9HrTIa0Q7v5h1sIYri-e8YVRrf-SwemOIOXCBLtrbOROiHUc-x9e1fo8b6RUa1KpVarQd2FPZFGObXLLcfwgE_C9oi9dTYX4VizERQpg8hKNweScQF8ubNEXw5AfVqzeyYdnubejxyPk9f5H62QGU9hQUrE_CmTUsA3nqYmeOTSz-dpcN8rps1eCF8StzddXAGEPwE2ZKxADPndZNgfJygysxG53TLzwsHt2tOAG3ivcDJ4hf
Abstract
BACKGROUND:
High concentrations of plasma 25-hydroxyvitamin D [25(OH)D], a marker of circulating vitamin D, have been associated with a lower risk of mortality in epidemiologic studies of multiple populations, but the association for Chinese adults aged ≥80 y (oldest old) remains unclear.
OBJECTIVE:
We investigated the association between plasma [25(OH)D] concentration and all-cause mortality among Chinese adults aged ≥80 y.
DESIGN:
The present study is a prospective cohort study of 2185 Chinese older adults (median age: 93 y). Prospective all-cause mortality data were analyzed for survival in relation to plasma 25(OH)D using Cox proportional hazards regression models, with adjustments for potential sociodemographic and lifestyle confounders and biomarkers. The associations were measured with HR and 95% CIs.
RESULTS:
The median plasma 25(OH)D concentration was 34.4 nmol/L at baseline. Over the 5466 person-year follow-up period, 1100 deaths were identified. Men and women were analyzed together as no effect modification by sex was found. After adjusting for multiple potential confounders, the risk of all-cause mortality decreased as the plasma 25(OH)D concentration increased (P-trend <0.01). Compared with the lowest age-specific quartile of plasma 25(OH)D, the adjusted HRs for mortality for the second, third, and fourth age-specific quartiles were 0.72 (95% CI: 0.57, 0.90), 0.73 (95% CI: 0.58, 0.93), and 0.61 (95% CI: 0.47, 0.81), respectively. The observed associations were broadly consistent across age and other subgroups. Sensitivity analyses generated similar results after excluding participants who died within 2 y of follow-up or after further adjustment for ethnicity and chronic diseases.
CONCLUSIONS:
A higher plasma 25-hydroxyvitamin D concentration was associated with a reduced risk of all-cause mortality among Chinese adults aged ≥80 y. This observed inverse association warrants further investigation in randomized controlled trials testing vitamin D supplementation in this age group.
KEYWORDS:
25-hydroxyvitamin D; Community-based; mortality; oldest old; survival

Garlic Supplementation Reduces Circulating C-reactive Protein, Tumor Necrosis Factor, and Interleukin-6 in Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Darooghegi Mofrad M, Milajerdi A, Koohdani F, Surkan PJ, Azadbakht L.
J Nutr. 2019 Apr 5. pii: nxy310. doi: 10.1093/jn/nxy310. [Epub ahead of print]
PMID: 30949665
Abstract
BACKGROUND:
Conflicting findings on the effects of garlic supplementation on inflammatory biomarkers have been observed in randomized clinical trials (RCTs).
OBJECTIVES:
The aim of this study was to summarize study results regarding the effects of garlic supplementation on serum inflammatory biomarkers in adults.
METHODS:
We searched Scopus, PubMed, Google Scholar and Cochrane library databases for relevant papers published until April 2018, using keywords such as "garlic" and "inflammatory biomarker." We included RCTs that 1) were conducted in adults, 2) examined the effects of garlic supplementation on inflammatory biomarkers compared to a control group, and 3) reported sufficient data on inflammatory biomarkers. Results were reported as weighted mean differences (WMD) with 95% CI using random effects models. Cochrane's Q and I-squared (I2) tests were used to determine heterogeneity among studies. Funnel plots and Egger's regression test were used to assess publication bias.
RESULTS:
Sixteen RCTs were included. Garlic doses ranged from 12 to 3600 mg/d, and intervention duration ranged from 2 to 52 wk. Garlic administration significantly reduced serum C-reactive protein (CRP) (n = 13) (WMD: -0.61 mg/L, 95% CI: -1.12, -0.11, P = 0.018, I2 = 76.9%), IL-6 (n = 5) (WMD: -0.73 ng/L, 95% CI: -1.06, -0.40, P < 0.001, I2 = 0%), and TNF (n = 7) (WMD: -0.26 ng/L, 95% CI: -0.41, -0.12, P < 0.001, I2 = 0.0%), compared to controls. However, the effect of garlic supplementation on serum adiponectin (n = 3) (WMD: 0.18 µg/L, 95% CI: -0.21, 0.57, P = 0.35, I2 = 60.7%) and leptin (n = 2) (WMD: -1.25 µg/L, 95% CI: -2.64, 0.14, P = 0.07, I2 = 0.0%) concentrations were not significant.
CONCLUSION:
In this meta-analysis of RCTs, we found that garlic supplementation reduced serum concentrations of CRP, TNF, IL-6, but did not affect serum adiponectin and leptin in adults. More RCTs are needed to test the effects of garlic supplementation on inflammation.
KEYWORDS:
diet; garlic; inflammation; meta-analysis

[AlPater]

Longevity and cause of death in male Wistar rats fed lifelong diets based on virgin olive oil, sunflower oil or fish oil.
Ramirez-Tortosa CL, Varela-López A, Navarro-Hortal MD, Ramos-Pleguezuelos FM, Márquez-Lobo B, Ramirez-Tortosa MC, Ochoa JJ, Battino M, Quiles JL.
J Gerontol A Biol Sci Med Sci. 2019 Apr 6. pii: glz091. doi: 10.1093/gerona/glz091. [Epub ahead of print]
PMID: 30953048
https://sci-hub.tw/10.1093/gerona/glz091
Abstract
Extending life by delaying the aging process have proven to be the most effective way to fight multiple chronic diseases in elderly adults. Evidence suggests that longevity is inversely related to unsaturation of membrane phospholipids. The present study investigated how different unsaturated dietary fats affect lifespan and cause death in male Wistar rats fed diets based on virgin olive oil (V), sunflower oil (S) or fish oil (F), which were supplemented or not with Coenzyme Q10 (CoQ10). Previous results suggest that individual longevity and survival probability at different ages may be modulated by an appropriate dietary fat treatment. Lifelong feeding with V or F diets would reduce death probability compared to feeding with S diet at certain ages, although the effects of V diet would be maintained for most of life. Furthermore, the addition of lower amounts of CoQ10 reduced mortality associated with S diet, but CoQ10 had no effect on survival when combined with virgin olive oil or fish oil. Supplementation with low doses of CoQ10 failed to increase the maximum lifespan potential of rats fed a V or F diet. No clear evidence showing that MUFA, n-3 PUFA or CoQ10 exerted the observed effects by modulating the rate of aging has been found.

[AlPater]

Vegetarian diet and risk of gout in two separate prospective cohort studies.
Chiu THT, Liu CH, Chang CC, Lin MN, Lin CL.
Clin Nutr. 2019 Mar 27. pii: S0261-5614(19)30129-3. doi: 10.1016/j.clnu.2019.03.016. [Epub ahead of print]
PMID: 30955983
https://sci-hub.tw/10.1016/j.clnu.2019.03.016
Abstract
BACKGROUNDS & AIMS:
Plant-based diets may target multiple pathways in gout pathogenesis (uric acid reduction and anti-inflammation) while improving gout associated cardiometabolic comorbidities. We aim to prospectively examine the relationship between a vegetarian diet and gout, and to explore if this relationship is independent of hyperuricemia.
METHODS:
We followed 4903 participants in the Tzu Chi Health Study (Cohort1, recruited in 2007-2009) and 9032 participants in the Tzu Chi Vegetarian Study (Cohort2, recruited in 2005) until end of 2014. Baseline serum uric acid was measured in Cohort1. Vegetarian status was assessed through a diet questionnaire that includes dietary habits and a food frequency questionnaire. Incidence of gout was ascertained by linkage to the National Health Insurance Database. Hazard Ratio of gout in vegetarians versus nonvegetarians was assessed by Cox regression, adjusted for age, sex, lifestyle and metabolic risk factors. Hyperuricemia was additionally adjusted in Cohort1.
RESULTS:
In Cohort1, lacto-ovo vegetarians had the lowest uric acid concentration, followed by vegans, then nonvegetarians (men: 6.05, 6.19, 6.32 mg/dL, respectively; women: 4.92, 4.96, 5.11 mg/dL, respectively); 65 gout cases occurred in the 29,673 person-years of follow-up; vegetarians experienced a lower risk of gout (without adjustment for hyperuricemia: HR: 0.33; 95% CI: 0.14, 0.79; with adjustment for hyperuricemia: HR: 0.40; 95% CI: 0.17, 0.97). In Cohort2, 161 gout cases occurred in the 83,019 person-years follow-up, and vegetarians also experienced a lower risk of gout (HR: 0.61; 95% CI: 0.41, 0.88).
CONCLUSION:
Taiwanese vegetarian diet is associated with lower risk of gout. This protective association may be independent of baseline hyperuricemia.
STUDY REGISTERED:
URL: https://www.clinicaltrials.gov. Unique Identifier: NCT03470584.
KEYWORDS:
Dietary patterns; Gout incidence; Uric acid; Vegetarian diet

Association Among Dietary Supplement Use, Nutrient Intake, and Mortality Among U.S. Adults: A Cohort Study.
Chen F, Du M, Blumberg JB, Ho Chui KK, Ruan M, Rogers G, Shan Z, Zeng L, Zhang FF.
Ann Intern Med. 2019 Apr 9. doi: 10.7326/M18-2478. [Epub ahead of print]
PMID: 30959527
Abstract
BACKGROUND:
The health benefits and risks of dietary supplement use are controversial.
OBJECTIVE:
To evaluate the association among dietary supplement use, levels of nutrient intake from foods and supplements, and mortality among U.S. adults.
DESIGN:
Prospective cohort study.
SETTING:
NHANES (National Health and Nutrition Examination Survey) data from 1999 to 2010, linked to National Death Index mortality data.
PARTICIPANTS:
30 899 U.S. adults aged 20 years or older who answered questions on dietary supplement use.
MEASUREMENTS:
Dietary supplement use in the previous 30 days and nutrient intake from foods and supplements. Outcomes included mortality from all causes, cardiovascular disease (CVD), and cancer.
RESULTS:
During a median follow-up of 6.1 years, 3613 deaths occurred, including 945 CVD deaths and 805 cancer deaths. Ever-use of dietary supplements was not associated with mortality outcomes. Adequate intake (at or above the Estimated Average Requirement or the Adequate Intake level) of vitamin A, vitamin K, magnesium, zinc, and copper was associated with reduced all-cause or CVD mortality, but the associations were restricted to nutrient intake from foods. Excess intake of calcium was associated with increased risk for cancer death (above vs. at or below the Tolerable Upper Intake Level: multivariable-adjusted rate ratio, 1.62 [95% CI, 1.07 to 2.45]; multivariable-adjusted rate difference, 1.7 [CI, -0.1 to 3.5] deaths per 1000 person-years), and the association seemed to be related to calcium intake from supplements (≥1000 mg/d vs. no use: multivariable-adjusted rate ratio, 1.53 [CI, 1.04 to 2.25]; multivariable-adjusted rate difference, 1.5 [CI, -0.1 to 3.1] deaths per 1000 person-years) rather than foods.
LIMITATIONS:
Results from observational data may be affected by residual confounding. Reporting of dietary supplement use is subject to recall bias.
CONCLUSION:
Use of dietary supplements is not associated with mortality benefits among U.S. adults.