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Lower baseline value and greater decline in BMD as independent risk factors for mortality in community dwelling elderly.
Kim KM, Moon JH, Choi SH, Lim S, Lim JY, Kim KW, Jang HC.
Bone. 2019 Jan 17. pii: S8756-3282(19)30018-3. doi: 10.1016/j.bone.2019.01.017. [Epub ahead of print]
PMID: 30660675
https://sci-hub.tw/10.1016/j.bone.2019.01.017
Abstract
Skeleton plays diverse roles via crosstalk between others, thus it is conceivable that lower BMD per se may reflect negative influences on health status and threats to life independent of fracture events. We investigated investigate the association between BMD and mortality, and to examine whether the rate of bone loss can predict future mortality in an elderly population. This study was conducted as a part of the Korean Longitudinal Study on Health and Aging, a community-based prospective study of Korean people aged 65 years and older that began in 2005. A total of 648 people (318 men and 330 women) were included. Dual energy X-ray absorptiometry were conducted at baseline and at 5 years. Mortality data were collected until the date of death or the last follow-up in December 2014. Osteoporosis in all skeletal sites significantly related to increased risk of mortality in men and women, but the associations were stronger for BMD in the femur neck and total hip than in the lumbar spine. A multivariable Cox proportional-hazards model showed that baseline BMD level was a significant independent predictor of increased all-cause mortality for all three skeletal sites in men, and for lumbar spine and total hip in women. Furthermore, faster bone loss of BMDs, as shown by the decline in BMD in the lumbar spine, femur neck, and total hip, was significantly related to increased risk of mortality after adjusting for all covariates in men. Faster BMD loss at femur neck was also related to the increased risks of mortality in women. Conclusively, both a lower baseline values and greater decline in BMD were associated with excess morality in community-dwelling elderly population; there associations were stronger in men than in women. This study emphasizes the importance of skeletal health for healthy aging, revealing lower bone mass and faster bone loss may be markers of poorer health that are driving excess mortality.
KEYWORDS:
Bone loss; Bone mineral density; Elderly; Mortality

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Associations of nutrient intakes with obesity and diabetes mellitus in the longitudinal medical surveys of Japanese-Americans.
Sugihiro T, Yoneda M, Ohno H, Oki K, Hattori N.
J Diabetes Investig. 2019 Jan 21. doi: 10.1111/jdi.13010. [Epub ahead of print]
PMID: 30663246
https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.13010
Abstract
INTRODUCTION:
Our previous survey of two Japanese populations, with different lifestyles but identical genetic dispositions, revealed that Japanese-Americans had different dietary intakes and higher prevalences of obesity and diabetes mellitus, compared to the native Japanese population. This study examined whether Westernized dietary habits could affect the development of obesity or diabetes.
MATERIALS AND METHODS:
This study included 765 individuals with normal glucose tolerance at baseline medical examinations (1986 or 1989 in Los Angeles and in 1988 or 1992 in Hawaii) who subsequently completed follow-up medical examinations several years later. The subjects were categorized at baseline as "lean" (576 individuals, body mass index of <25 kg/m2 ) or "obese" (189 individuals, body mass index of ≥25 kg/m2 ). Nutrient intakes were analyzed for associations with the development of obesity or diabetes using Cox's proportional hazard model.
RESULTS:
Forty-one lean subjects developed diabetes, which was not associated with any nutrient intakes (mean follow-up: 10.8 ± 6.6 years). Thirty-six obese subjects developed diabetes, which was positively associated with intakes of animal protein, animal fat, and saturated fatty acid (mean follow-up: 10.7 ± 6.3 years). Eighty-five lean subjects became obese, which was positively associated with intakes of simple carbohydrates, sugar, and fructose, as well as inversely associated with intakes of vegetable protein and complex carbohydrates (mean follow-up: 10.4 ± 6.5 years).
CONCLUSIONS:
In the Japanese-Americans, different nutrient intakes affected the development of obesity and diabetes. Moreover, the associations of nutrient intakes with diabetes development varied according to the presence or absence of obesity.
KEYWORDS:
diabetes mellitus; nutrient intake; obesity

Central adiposity in relation to risk of liver cancer in Chinese adults: A prospective study of 0.5 million people.
Pang Y, Kartsonaki C, Guo Y, Chen Y, Yang L, Bian Z, Bragg F, Millwood IY, Yu C, Lv J, Chen J, Li L, Holmes MV, Chen Z.
Int J Cancer. 2019 Jan 21. doi: 10.1002/ijc.32148. [Epub ahead of print]
PMID: 30665257
Abstract
Central adiposity is associated with liver cancer risk beyond general adiposity in Western populations. However, there is little prospective evidence in East Asian populations who are more likely to have central adiposity at given BMI levels. The prospective China Kadoorie Biobank recruited 512,713 adults aged 30-79 years from 10 diverse areas. During 10 years follow-up, 2847 incident cases of liver cancer were identified. Cox regression was used to estimate adjusted hazard ratios (HR) for liver cancer associated with central adiposity, excluding individuals with cancers and liver diseases at baseline and the first five years of follow-up (1049 incident liver cancer cases). Overall, mean waist circumference (WC) was 82.2 (SD 9.8) cm in men and 79.1 (9.5) cm in women. Central adiposity showed positive associations with liver cancer risk. Associations were strongest for WC and waist-to-hip ratio (WHR), with adjusted HRs per 1-SD of 1.09 (95%CI 1.01-1.18) and 1.12 (1.02-1.23), respectively. The positive associations became stronger when simultaneously adjusting for BMI (1.26 [1.09-1.46] and 1.14 [1.02-1.28]). The positive association of central obesity (WC ≥90 cm in men and ≥80 cm in women) with liver cancer increased progressively with the number of other presenting metabolic risk factors (physical inactivity, diabetes, and hypertension), with HRs of 1.07 (0.90-1.28), 1.17 (1.00-1.38), and 1.91 (1.40-2.59) in those with one, two, and three factors (p for trend 0.006). In this relatively lean Chinese population, there were positive associations of central adiposity with risk of liver cancer, with WHR and WC showing the strongest associations.
KEYWORDS:
Chinese; central adiposity; cohort study; liver cancer

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Glucose & energy homeostasis: Lessons from animal studies.
Giridharan NV.
Indian J Med Res. 2018 Nov;148(5):659-669. doi: 10.4103/ijmr.IJMR_1737_18. Review.
PMID: 30666991
http://www.ijmr.org.in/temp/IndianJMedRes1485659-3718431_101944.pdf
Abstract
Glucose in our body is maintained within a narrow range by the humoral control and a 'lipostat' system regulated by leptin from adipose tissues, which keep our accumulated fat stores in check. Any disturbance in this delicately poised homeostasis could be disastrous as it can lead to obesity and its associated metabolic manifestations. Laboratory animals, especially rodents, have contributed to our knowledge in understanding this physiological mechanism through an array of genetic and non-genetic animals developed over the years. Two rat mutant obese models-Wistar inbred at National Institute of Nutrition (WNIN)/Ob-obese rats with normal glucose levels and WNIN/GR-Ob-obese with impaired glucose tolerance were developed in the National Centre for Laboratory Animal Sciences (Now ICMR-National Animal Resource Facility for Biomedical Research) at Hyderabad, India. These animals are unique, as, unlike the earlier models, they show all types of degenerative disorders associated with obesity, within a single system. Thus they show impairment in all the major organs of the body - liver, pancreas, kidney, bones, muscles, gonads, brain, eyes, and are sensitive to diet manipulations, have compromised immunity, often develop tumours and have reduced life span. One may argue that there are limitations to one's interpretations from animal studies to human application, but then one cannot shut one's eyes to the new lessons they have taught us in modifying our life styles.
KEYWORDS:
Animal models; energy; glucose; homeostasis; immunity obesity; leptin; obesity genes; retinal disorders

DNA methylation GrimAge strongly predicts lifespan and healthspan.
Lu AT, Quach A, Wilson JG, Reiner AP, Aviv A, Raj K, Hou L, Baccarelli AA, Li Y, Stewart JD, Whitsel EA, Assimes TL, Ferrucci L, Horvath S.
Aging (Albany NY). 2019 Jan 21. doi: 10.18632/aging.101684. [Epub ahead of print]
PMID: 30669119
https://s3-us-west-1.amazonaws.com/paperchase-aging/pdf/W8jwg5cHAzptsYSEH.pdf
Abstract
It was unknown whether plasma protein levels can be estimated based on DNA methylation (DNAm) levels, and if so, how the resulting surrogates can be consolidated into a powerful predictor of lifespan. We present here, seven DNAm-based estimators of plasma proteins including those of plasminogen activator inhibitor 1 (PAI-1) and growth differentiation factor 15. The resulting predictor of lifespan, DNAm GrimAge (in units of years), is a composite biomarker based on the seven DNAm surrogates and a DNAm-based estimator of smoking pack-years. Adjusting DNAm GrimAge for chronological age generated novel measure of epigenetic age acceleration, AgeAccelGrim.Using large scale validation data from thousands of individuals, we demonstrate that DNAm GrimAge stands out among existing epigenetic clocks in terms of its predictive ability for time-to-death (Cox regression P=2.0E-75), time-to-coronary heart disease (Cox P=6.2E-24), time-to-cancer (P= 1.3E-12), its strong relationship with computed tomography data for fatty liver/excess visceral fat, and age-at-menopause (P=1.6E-12). AgeAccelGrim is strongly associated with a host of age-related conditions including comorbidity count (P=3.45E-17). Similarly, age-adjusted DNAm PAI-1 levels are associated with lifespan (P=5.4E-28), comorbidity count (P= 7.3E-56) and type 2 diabetes (P=2.0E-26). These DNAm-based biomarkers show the expected relationship with lifestyle factors including healthy diet and educational attainment.Overall, these epigenetic biomarkers are expected to find many applications including human anti-aging studies.
KEYWORDS:
DNA methylation; epigenetics; mortality; proteomics

Risk of all-cause and CHD mortality in women versus men with type 2 diabetes: a systematic review and meta-analysis.
Xu G, You D, Wong L, Duan D, Kong F, Zhang X, Zhao J, Xing W, Li L, Han L.
Eur J Endocrinol. 2019 Jan 1. pii: EJE-18-0792.R1. doi: 10.1530/EJE-18-0792. [Epub ahead of print]
PMID: 30668524
Abstract
OBJECTIVE:
Previous studies have shown sex-specific differences in all-cause and CHD mortality in type 2 diabetes. We performed a systematic review and meta-analysis to provide a global picture of the estimated influence of type 2 diabetes on the risk of all-cause and CHD mortality in women versus men.
METHODS:
We systematically searched PubMed, Embase, and Web of Science for studies published from their starting dates to 7 Aug 2018. The sex-specific hazard ratios (HRs) and their pooled ratio (women vs. men) of all-cause and CHD mortality associated with type 2 diabetes were obtained through an inverse-variance weighted random-effects meta-analysis. Subgroup analyses were used to explore potential sources of heterogeneity.
RESULTS:
The 35 analyzed prospective cohort studies included 2,314,292 individuals, among whom 254,038 all-cause deaths occurred. The pooled women vs. men ratio of the HRs for all-cause and CHD mortality were 1.17 (95% CI 1.12-1.23, I2=81.6%) and 1.97 (95% CI 1.49-2.61, I2=86.4%), respectively. The pooled estimate of the HR for all-cause mortality was approximately 1.30 in articles in which the duration of follow-up longer than 10 years, and 1.10 in articles in which the duration of follow-up less than 10 years. The pooled HRs for all-cause mortality in patients with type 2 diabetes was 2.33 (95% CI 2.02-2.69) in women and 1.91 (95% CI 1.72-2.12) in men, compared with their healthy counterparts.
CONCLUSIONS:
The effect of diabetes on all-cause and CHD mortality is approximately 17% and 97% greater, respectively, for women than for men.

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Objective versus Self-Reported Energy Intake Changes During Low-Carbohydrate and Low-Fat Diets.
Guo J, Robinson JL, Gardner CD, Hall KD.
Obesity (Silver Spring). 2019 Jan 22. doi: 10.1002/oby.22389. [Epub ahead of print]
PMID: 30672127
Abstract
OBJECTIVE:
This study aimed to compare self-reported with objective measurements of energy intake changes (∆EI) during a 1-year weight-loss intervention with subjects randomized to low-carbohydrate versus low-fat diets.
METHODS:
Repeated body weight measurements were used as inputs to an objective mathematical model to calculate ∆EIModel and to compare with self-reported energy intake changes assessed by repeated 24-hour recalls (∆EIRecall ).
RESULTS:
∆EIRecall indicated a relatively persistent state of calorie restriction of ~500 to 600 kcal/d at 3, 6, and 12 months with no significant differences between the diets. ∆EIModel demonstrated large early decreases in calorie intake > 800 kcal/d followed by an exponential return to ~100 kcal/d below baseline at the end of the year. Accounting for self-reported physical activities did not materially affect the results. Discrepancies between ∆EIModel and ∆EIRecall became progressively greater over time. The low-carbohydrate diet resulted in ∆EIModel that was 162 ± 53 kcal/d lower than the low-fat diet over the first 3 months (P  =  0.002), but no significant diet differences were found thereafter.
CONCLUSIONS:
Self-reported ∆EI measurements were inaccurate. Model-based calculations of ∆EI found that instructions to follow the low-carbohydrate diet resulted in greater calorie restriction than the low-fat diet in the early phases of the intervention, but these diet differences were not sustained.

Postprandial Effects of Blueberry (Vaccinium angustifolium) Consumption on Glucose Metabolism, Gastrointestinal Hormone Response, and Perceived Appetite in Healthy Adults: A Randomized, Placebo-Controlled Crossover Trial.
Stote K, Corkum A, Sweeney M, Shakerley N, Kean T, Gottschall-Pass K.
Nutrients. 2019 Jan 19;11(1). pii: E202. doi: 10.3390/nu11010202.
PMID: 30669469
https://www.mdpi.com/2072-6643/11/1/202/htm
Abstract
The consumption of blueberries, as well as the phenolic compounds they contain, may alter metabolic processes related to type 2 diabetes. The study investigated the effects of adding 140 g of blueberries to a higher-carbohydrate breakfast meal on postprandial glucose metabolism, gastrointestinal hormone response, and perceived appetite. As part of a randomized crossover design study, 17 healthy adults consumed a standardized higher-carbohydrate breakfast along with 2 treatments: (1) 140 g (1 cup) of whole blueberries and (2) a placebo gel (matched for calories, sugars, and fiber of the whole blueberries). Each subject participated in two 2-h meal tests on separate visits ≥8 days apart. Venous blood samples and perceived appetite ratings using visual analog scales were obtained prior to and at 30, 60, 90, and 120 min after consuming the breakfast meals. Results show that glucose metabolism, several gastrointestinal hormones, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY) concentrations and perceived appetite did not change significantly with blueberry consumption. However, pancreatic polypeptide (PP) concentrations were statistically significantly higher (p = 0.0367), and the concentrations were higher during 30, 60, 90, and 120 min after consumption of the blueberry breakfast meal than the placebo breakfast meal. Additional research is needed to determine whether blueberries and other flavonoid-rich foods reduce type 2 diabetes risk by modifying gastrointestinal hormones and perceived appetite.
KEYWORDS:
anthocyanins; blueberries; gastrointestinal hormones; glucose metabolism; perceived appetite
[K.S., M.S. and K.G.-P. received grant support from the Wild Blueberry Association of North American.]

Red meat, processed meat, and other dietary protein sources and risk of overall and cause-specific mortality in The Netherlands Cohort Study.
van den Brandt PA.
Eur J Epidemiol. 2019 Jan 23. doi: 10.1007/s10654-019-00483-9. [Epub ahead of print]
PMID: 30673923
https://link.springer.com/content/pdf/10.1007%2Fs10654-019-00483-9.pdf
Abstract
Processed meat and red meat have been associated with increased mortality, but studies are inconsistent and few have investigated substitution by other protein sources. The relationship of overall and causes-specific mortality with red meat, processed meat, and other dietary protein sources was investigated in The Netherlands Cohort Study. In 1986, 120,852 men and women aged 55-69 years provided information on dietary and lifestyle habits. Mortality follow-up until 1996 consisted of linkage to statistics Netherlands. Multivariable case-cohort analyses were based on 8823 deaths and 3202 subcohort members with complete data on diet and confounders. Red meat (unprocessed) intake was not associated with overall and cause-specific mortality. Processed meat intake was significantly positively related to overall mortality: HR (95% CI) comparing highest versus lowest quintile, 1.21 (1.02-1.44) with Ptrend = 0.049. Significant associations were observed for cardiovascular [HR Q5 vs. Q1, 1.26 (1.01-1.26)] and respiratory [HR = 1.79 (1.19-2.67)], but not cancer mortality [HR = 1.16 (0.97-1.39)]. Adjustment for nitrite intake attenuated these associations which became nonsignificant: HRs Q5 versus Q1 (95% CI) were: 1.10 (0.77-1.55) for total, 1.09 (0.71-1.67) for cardiovascular, 1.44 (0.68-3.05) for respiratory, and 1.11 (0.78-1.58) for cancer mortality. Nitrite was significantly associated with overall, CVD and respiratory mortality. Poultry intake was significantly inversely related to cancer and overall mortality. While fish intake showed positive associations, nut intake showed inverse associations with all endpoints. Replacing processed meat with a combination of poultry, eggs, fish, pulses, nuts and low-fat dairy was associated with lower risks of overall, cardiovascular and respiratory mortality. Processed meat was related to increased overall, CVD and respiratory mortality, potentially due to nitrite. Substituting processed meat with other protein sources was associated with lower mortality risks.
KEYWORDS:
Cardiovascular diseases; Cohort studies; Mortality; Neoplasms; Processed meat; Protein sources; Red meat; Respiratory diseases

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Prospects of Pharmacological Interventions to Organismal Aging.
Hillson O, Gonzalez S, Rallis C.
Biomol Concepts. 2018 Dec 31;9(1):200-215. doi: 10.1515/bmc-2018-0018.
PMID: 30676997
https://sci-hub.tw/10.1515/bmc-2018-0018
Abstract
Intense research in the areas of cellular and organismal aging using diverse laboratory model systems has enriched our knowledge in the processes and the signalling pathways involved in normal and pathological conditions. The field finds itself in a position to take decisive steps towards clinical applications and interventions not only for targeted age-related diseases such as cardiovascular conditions and neurodegeneration but also for the modulation of health span and lifespan of a whole organism. Beyond nutritional interventions such as dietary restriction without malnutrition and various regimes of intermittent fasting, accumulating evidence provides promise for pharmacological interventions. The latter, mimic caloric or dietary restriction, tune cellular and organismal stress responses, affect the metabolism of microbiome with subsequent effects on the host or modulate repair pathways, among others. In this mini review, we summarise some of the evidence on drugs that can alter organismal lifespan and the prospects they might offer for promoting healthspan and delaying age-related diseases.
KEYWORDS:
TOR; Torin; aspirin; insulin growth signalling pathway; lifespan; metformin; rapalogs; rapamycin

Association of fried food consumption with all cause, cardiovascular, and cancer mortality: prospective cohort study.
Sun Y, Liu B, Snetselaar LG, Robinson JG, Wallace RB, Peterson LL, Bao W.
BMJ. 2019 Jan 23;364:k5420. doi: 10.1136/bmj.k5420.
PMID: 30674467
https://sci-hub.tw/10.1136/bmj.k5420
Abstract
OBJECTIVE:
To examine the prospective association of total and individual fried food consumption with all cause and cause specific mortality in women in the United States.
DESIGN:
Prospective cohort study.
SETTING:
Women's Health Initiative conducted in 40 clinical centers in the US.
PARTICIPANTS:
106 966 postmenopausal women aged 50-79 at study entry who were enrolled between September 1993 and 1998 in the Women's Health Initiative and followed until February 2017.
MAIN OUTCOME MEASURES:
All cause mortality, cardiovascular mortality, and cancer mortality.
RESULTS:
31 558 deaths occurred during 1 914 691 person years of follow-up. For total fried food consumption, when comparing at least one serving per day with no consumption, the multivariable adjusted hazard ratio was 1.08 (95% confidence interval 1.01 to 1.16) for all cause mortality and 1.08 (0.96 to 1.22) for cardiovascular mortality. When comparing at least one serving per week of fried chicken with no consumption, the hazard ratio was 1.13 (1.07 to 1.19) for all cause mortality and 1.12 (1.02 to 1.23) for cardiovascular mortality. For fried fish/shellfish, the corresponding hazard ratios were 1.07 (1.03 to 1.12) for all cause mortality and 1.13 (1.04 to 1.22) for cardiovascular mortality. Total or individual fried food consumption was not generally associated with cancer mortality.
CONCLUSIONS:
Frequent consumption of fried foods, especially fried chicken and fried fish/shellfish, was associated with a higher risk of all cause and cardiovascular mortality in women in the US.

Effect of maternal pre-pregnancy BMI and weekly gestational weight gain on the development of infants.
Li C, Zeng L, Wang D, Dang S, Chen T, Watson V, Yan H.
Nutr J. 2019 Jan 23;18(1):6. doi: 10.1186/s12937-019-0432-8.
PMID: 30674315
https://nutritionj.biomedcentral.com/track/pdf/10.1186/s12937-019-0432-8
Abstract
OBJECTIVE:
The aim of the present study is to identify the average effect across different time points and to specify the time effects of maternal pre-pregnancy BMI and weekly gestational weight gain on the mental development and physical growth of infants.
METHODS:
The present cohort study used a repeated measures study design that began in 2004 with follow up at 3, 6, 12, 18, and 24 months of age. The participants were a subset from a controlled, cluster-randomized, double-blind trial. Bayley Scales of Infant Development (BSID) were used to estimate the mental development of infants. A generalized estimating equation linear model was used to estimate the effects of maternal BMI and weight gain.
RESULTS:
The average effect of maternal BMI and weight gain on the weight for age Z scores (WAZ), length for age Z scores (LAZ) and mental development index (MDI) across the different time points of infants was significant. In addition, the maternal BMI and weight gain were positively and significantly associated with the WAZ and LAZ in infants of different ages. However, the effect of weekly gestational weight gain was significant only during the earlier period of life (3 months, Coefficient: 11.15, 95%CI: 4.89-17.41).
CONCLUSIONS:
Our results indicate positive effects of pre-pregnancy and prenatal nutrition on the physical growth of infants. Weekly gestational weight gain of the pregnant women had a positive effect on the mental development of the infants, but this effect appears to decline over time.
KEYWORDS:
Development of infants; Maternal pre-pregnancy BMI; Weekly gestational weight gain

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Magnesium and health outcomes: an umbrella review of systematic reviews and meta-analyses of observational and intervention studies.
Veronese N, Demurtas J, Pesolillo G, Celotto S, Barnini T, Calusi G, Caruso MG, Notarnicola M, Reddavide R, Stubbs B, Solmi M, Maggi S, Vaona A, Firth J, Smith L, Koyanagi A, Dominguez L, Barbagallo M.
Eur J Nutr. 2019 Jan 25. doi: 10.1007/s00394-019-01905-w. [Epub ahead of print]
PMID: 30684032
Abstract
PURPOSE:
To map and grade all health outcomes associated with magnesium (Mg) intake and supplementation using an umbrella review.
METHODS:
Umbrella review of systematic reviews with meta-analyses of observational studies and randomized controlled trials (RCTs) using placebo/no intervention as control group. We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their p values, 95% prediction intervals, heterogeneity, small-study effects and excess significance. For meta-analyses of RCTs, outcomes with a random-effect p value < 0.005 and a high-GRADE assessment were classified as strong evidence.
RESULTS:
From 2048 abstracts, 16 meta-analyses and 55 independent outcomes were included (36 in RCTs and 19 in observational studies). In RCTs of Mg versus placebo/no active treatment, 12 over 36 outcomes reported significant results (p < 0.05). A strong evidence for decreased need for hospitalization in pregnancy and for decreased risk of frequency and intensity of migraine relapses in people with migraine was observed using the GRADE assessment. In observational studies, 9/19 outcomes were significant (p < 0.05). However, only one outcome presented highly suggestive evidence (lower incidence of type 2 diabetes in people with higher Mg intake at baseline) and one suggestive (lower incidence of stroke associated with higher Mg intake at baseline).
CONCLUSION:
Strong evidence according to the GRADE suggests that Mg supplementation can decrease the risk of hospitalization in pregnant women and reduce the intensity/frequency of migraine. Higher Mg intake is associated with a decreased risk of type 2 diabetes and stroke with highly suggestive and suggestive evidence, respectively, in observational studies.
KEYWORDS:
Diabetes; Magnesium; Meta-analysis; Pregnancy; Stroke; Umbrella review

Vegetable Nitrate Intakes Are Associated with Reduced Self-Reported Cardiovascular-Related Complications within a Representative Sample of Middle-Aged Australian Women, Prospectively Followed up for 15 Years.
Jackson JK, Patterson AJ, MacDonald-Wicks LK, Forder PM, Blekkenhorst LC, Bondonno CP, Hodgson JM, Ward NC, Holder C, Oldmeadow C, Byles JE, McEvoy MA.
Nutrients. 2019 Jan 22;11(2). pii: E240. doi: 10.3390/nu11020240.
PMID: 30678264
https://www.mdpi.com/2072-6643/11/2/240/htm
Abstract
Nitric oxide (NO) facilitates anti-atherosclerotic effects. Vegetables are a major source of dietary nitrate. Experimental data indicates that dietary nitrate can significantly reduce major risk factors for atherosclerosis and subsequent cardiovascular disease (CVD), as nitrate can be metabolized to produce NO via the nitrate-nitrite-NO pathway. The purpose of this study was to prospectively investigate the association between habitual dietary nitrate intakes and the incidence of self-reported CVD-related complications within a representative sample of middle-aged Australian women (1946⁻1951 cohort of the Australian Longitudinal Study on Women's Health). Women free from disease at baseline who had completed the food frequency questionnaire data were included. Generalized estimating equations were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) across quartiles for nitrate intakes. Of the 5324 women included for analysis, there were 1951 new cases of CVD-related complications over 15-years of follow-up. Women reporting higher total dietary nitrate intakes (Q4 > 78.2 mg/day) and vegetable nitrate intakes (Q4 > 64.4 mg/day) were 25% and 27% reduced risk of developing CVD-related complications respectively, compared with women reporting low total (Q1 < 45.5 mg/day) and vegetable nitrate intakes (Q1 < 34.8 mg/day). Our findings were consistent with other observational data indicating that dietary nitrate may explain some of the cardiovascular benefits of vegetable consumption.
KEYWORDS:
cardiovascular disease; dietary nitrate; heart disease; hypertension; non-vegetable nitrate; stroke; thrombosis; vegetable nitrate

Dietary intake of fish, n-3 polyunsaturated fatty acids, and risk of inflammatory bowel disease: a systematic review and meta-analysis of observational studies.
Mozaffari H, Daneshzad E, Larijani B, Bellissimo N, Azadbakht L.
Eur J Nutr. 2019 Jan 24. doi: 10.1007/s00394-019-01901-0. [Epub ahead of print] Review.
PMID: 30680455
Abstract
PURPOSE:
Fish consumption and dietary intake of n-3 polyunsaturated acids (PUFAs) may be associated with inflammatory bowel disease (IBD). We aimed to conduct a systematic review and summarize published articles on the association between fish consumption and dietary intake of n-3 PUFAs with the risk of IBD.
METHODS:
PubMed, Scopus, and Web of Science databases were used to conduct a comprehensive search and identify eligible literature published prior to January 2019. Fixed-effects model or random-effects models (DerSimonian-Laird method) were applied to pool the effect sizes. Cochrane Q test was used to trace the potential source of heterogeneity across studies.
RESULTS:
12 studies (5 prospective and 7 case-control) were included in the systematic review, which ten of them were eligible for inclusion in the meta-analysis. Studies were included a total sample size of 282610 participants which 2002 of them were cases of IBD [1061 Crohn's disease (CD) and 937 ulcerative colitis (UC)]. A negative association was found between fish consumption and the incidence of CD (pooled effect size: 0.54, 95%CI: 0.31-0.96, P = 0.03). There was no relationship between total dietary n-3 PUFAs intake and IBD (pooled effect size: 1.17, 95%CI: 0.80-1.72, P = 0.41). A significant inverse association was observed between dietary long-chain n-3 PUFAs and the risk of UC (pooled effect size: 0.75, 95%CI: 0.57-0.98, P = 0.03). Moreover, no association was found between α-Linolenic acid (ALA) and IBD (pooled effect size: 1.17, 95%CI: 0.63-2.17, P = 0.62).
CONCLUSIONS:
Findings showed a negative association between fish consumption and the risk of CD. Moreover, there was a significant inverse association between dietary long-chain n-3 PUFAs and the risk of UC.
KEYWORDS:
Fish; Inflammatory bowel disease; Meta-analysis; Omega-3

High ankle-brachial index and risk of cardiovascular or all-cause mortality: A meta-analysis.
Gu X, Man C, Zhang H, Fan Y.
Atherosclerosis. 2019 Jan 2;282:29-36. doi: 10.1016/j.atherosclerosis.2018.12.028. [Epub ahead of print] Review.
PMID: 30682724
Abstract
BACKGROUND AND AIMS:
Studies on high ankle-brachial index (ABI) to predict mortality risk have yielded conflicting results. This meta-analysis aimed to evaluate the association between abnormally high ABI and risk of cardiovascular or all-cause mortality.
METHODS:
Pubmed and Embase databases were systematically searched for relevant articles published up to August 15, 2018. Longitudinal observational studies that evaluated the association between abnormally high ABI at baseline and risk of cardiovascular or all-cause mortality were included. Pooled results were expressed as risk ratio (RR) with 95% confidence intervals (CI) for the abnormal high versus the reference normal ABI category.
RESULTS:
Eighteen studies enrolling 60,467 participants were included. Abnormally high ABI was associated with an increased risk of all-cause mortality (RR 1.50; 95% CI 1.27-1.77) and cardiovascular mortality (RR 1.84; 95% CI 1.54-2.20). The pooled RR of all-cause mortality was 1.45 (95% CI 1.16-1.82) for the general population, 1.67 (95% CI 1.03-2.71) for chronic kidney disease (CKD)/hemodialysis patients, and 1.55 (95% CI 1.10-2.20) for suspected or established cardiovascular disease (CVD) patients, respectively. The pooled RR of cardiovascular mortality was 1.84 (95% CI 1.43-2.38) for the general population, 4.28 (95% CI 2.18-8.40) for CKD/hemodialysis patients, and 1.58 (95% CI 1.22-2.05) for suspected or established CVD patients, respectively.
CONCLUSIONS:
Abnormally high ABI is independently associated with an increased risk of all-cause mortality. However, interpretation of the association between abnormally high ABI and cardiovascular mortality should be done with caution because of the likelihood of publication bias.
KEYWORDS:
All-cause mortality; Ankle-brachial index; Cardiovascular mortality; Meta-analysis

Lifestyle factors and visceral adipose tissue: Results from the PREDIMED-PLUS study.
Galmes-Panades AM, Konieczna J, Abete I, Colom A, Rosique-Esteban N, Zulet MA, Vázquez Z, Estruch R, Vidal J, Toledo E, Babio N, Fiol M, Casas R, Vera J, Buil-Cosiales P, de Paz JA, Goday A, Salas-Salvadó J, Martínez JA, Romaguera D; PREDIMED-Plus investigators.
PLoS One. 2019 Jan 25;14(1):e0210726. doi: 10.1371/journal.pone.0210726. eCollection 2019.
PMID: 30682078
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210726
Abstract
BACKGROUND:
Visceral adipose tissue (VAT) is a strong predictor of cardiometabolic health, and lifestyle factors may have a positive influence on VAT depot. This study aimed to assess the cross-sectional associations between baseline levels of physical activity (PA), sedentary behaviours (SB) and adherence to the Mediterranean diet (MedDiet) with VAT depot in older individuals with overweight/obesity and metabolic syndrome.
METHODS:
Baseline data of the PREDIMED-Plus study including a sample of 1,231 Caucasian men and women aged 55-75 years were used. Levels of leisure-time PA (total, light, and moderate-to-vigorous, in METs·min/day) and SB (total and TV-viewing, in h/day) were evaluated using validated questionnaires. Adherence to the MedDiet was evaluated using a 17-item energy-restricted MedDiet (erMedDiet) screener. The chair-stand test was used to estimate the muscle strength. VAT depot was assessed with DXA-CoreScan. Multivariable adjusted linear regression models were used to evaluate the association between lifestyle factors and VAT. For the statistics we had used multiadjusted linear regression models.
RESULTS:
Total leisure-time PA (100 METs·min/day: β -24.3g, -36.7;-11.9g), moderate-to-vigorous PA (β -27.8g, 95% CI -40.8;-14.8g), chair-stand test (repeat: β -11.5g, 95% CI -20.1;-2.93g) were inversely associated, and total SB (h/day: β 38.2g, 95% CI 14.7;61.7) positively associated with VAT. Light PA, TV-viewing time and adherence to an erMedDiet were not significantly associated with VAT.
CONCLUSIONS:
In older adults with overweigh/obesity and metabolic syndrome, greater PA, muscle strength, and lower total SB were associated with less VAT depot. In this study, adherence to an erMedDiet was not associated with lower VAT.

Androgen receptor and soy isoflavones in prostate cancer.
Sivoňová MK, Kaplán P, Tatarková Z, Lichardusová L, Dušenka R, Jurečeková J.
Mol Clin Oncol. 2019 Feb;10(2):191-204. doi: 10.3892/mco.2018.1792. Epub 2018 Dec 11. Review.
PMID: 30680195
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327222/pdf/mco-10-02-0191.pdf
Abstract
Androgens and androgen receptor (AR) play a critical role not only in normal prostate development, but also in prostate cancer. For that reason, androgen deprivation therapy (ADT) is the primary treatment for prostate cancer. However, the majority of patients develop castration-resistant prostate cancer, which eventually leads to mortality. Novel therapeutic approaches, including dietary changes, have been explored. Soy isoflavones have become a focus of interest because of their positive health benefits on numerous diseases, particularly hormone-related cancers, including prostate and breast cancers. An important strategy for the prevention and/or treatment of prostate cancer might thus be the action of soy isoflavones on the AR signaling pathway. The current review article provides a detailed overview of the anticancer potential of soy isoflavones (genistein, daidzein and glycitein), as mediated by their effect on AR.
KEYWORDS:
androgen receptor; daidzein; genistein; glycitein; prostate cancer; soy isoflavones; steroids

Nutrients mediate bioavailability and turnover of proteins in mammals.
Nie C, Xie F, Ma N, Bai Y, Zhang W, Ma X.
Curr Protein Pept Sci. 2019 Jan 24. doi: 10.2174/1389203720666190125111235. [Epub ahead of print]
PMID: 30678625
Abstract
As a major component of biologically active compounds in the body, proteins contribute to the synthesis of body tissues, for the renewal and growth of the body. The high level of dietary protein and the imbalance of amino acid (AA) composition in mammals result in metabolic disorders, inefficient utilization of protein resources and increased nitrogen excretion. Fortunately, nutritional interventions can be an effective way of attenuating the nitrogen excretion and increasing protein utilization, which include, but are not limited to, formulating the AA balance and protein-restricted diet supplementing with essential AAs, and adding probiotics in the diet. This review highlights recent advances in the turnover of dietary proteins and mammal's metabolism for health, in order to improve protein bioavailability through nutritional approach.
KEYWORDS:
amino acid balance; bioavailability; dietary protein; gut microbiota; turnover

This season's flu shot far more effective than last year's, Canadian team finds Vaccine's effectiveness in preventing H1N1 comparable to that found in Australia
The Canadian Press · Posted: Jan 24, 2019
https://www.cbc.ca/news/health/flu-vaccine-1.4991431

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Systematic review of modifiable risk factors for kidney cancer.
Al-Bayati O, Hasan A, Pruthi D, Kaushik D, Liss MA.
Urol Oncol. 2019 Jan 24. pii: S1078-1439(18)30502-7. doi: 10.1016/j.urolonc.2018.12.008. [Epub ahead of print] Review.
PMID: 30685335
https://sci-hub.tw/10.1016/j.urolonc.2018.12.008
Abstract
To perform a systematic review of modifiable risk factors associated with the incidence of renal cell cancer (RCC). A systematic search of the literature was conducted using PubMed, Cochrane, and Web of Science databases from January 1996 until August 2017. We also extracted articles from the reference lists of identified studies and reviews. We targeted modifiable risk factors for RCC to include exercise, smoking, alcohol, diet, obesity, hypertension, and diabetes. We utilized predefined inclusion criteria and the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. We identified a total of 464 relevant articles and excluded 209 via title and 130 after abstract review. We thoroughly reviewed a total of 125 manuscripts. Seven supplementary tables describe (a) case controls and (b) prospective cohort studies. We summarize the tables in figures to visualize the overall impact of these studies association (beneficial, harmful, or null) with RCC. Total physical activity if beneficial (10/12 studies), smoking is harmful (13/14 studies), alcohol was protective (i.e., beneficial, 13/16 studies), diet was indeterminate (13 beneficial, 13 harmful, and 9 nulls), obesity and hypertension were overwhelmingly harmful (36/36 studies and 17/18, respectively), and diabetes was detrimental (23/27 studies). Modifiable risk factors play an essential role in the development of RCC, and we should develop targeted RCC prevention strategies in at-risk individuals.
KEYWORDS:
Alcohol; Diabetes; Diet; Epidemiology; Hypertension; Kidney cancer; Modifiable risk; Obesity; Outcomes; Smoking
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A prospective study of alcohol consumption and renal cell carcinoma risk.
Karami S, Daugherty SE, Purdue MP.
Int J Cancer. 2015 Jul 1;137(1):238-42. doi: 10.1002/ijc.29359. Epub 2014 Dec 10.
PMID: 25431248 Free PMC Article
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405442/
Abstract
Recent epidemiological studies suggest that alcohol consumption may reduce renal cell carcinoma (RCC) risk, although inconsistent findings have been reported by sex and alcoholic beverage type. To better understand the relationship between alcohol consumption and RCC risk, we conducted an analysis within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We followed up participants in the analytic cohort (N = 107,998) through 2010 for incident RCC (N = 408), and computed hazard ratios (HRs) and 95% confidence intervals (CIs) for alcohol intake using Cox regression with adjustment for age, sex, race, study center, hypertension, body mass index, and smoking status. In this study population increasing alcohol consumption was associated with reduced RCC risk compared to non-drinkers (>9.75 g day(-1) : HR, 0.67; 95%CI, 0.50 to 0.89; p trend = 0.002). We observed similar patterns of association for men and women as well as by alcohol beverage type. In analyses stratified by smoking status, the inverse association with consumption was apparent for ever smokers (HR, 0.51; 95%CI, 0.36 to 0.73; p trend<0.0001) but not among never smokers (HR, 1.08; 95%CI, 0.66 to 1.76; P trend = 0.78; p interaction = 0.01). Our study findings offer further support that alcohol consumption is associated with reduced RCC risk, regardless of sex or alcoholic beverage type. The finding of interaction with smoking is novel and requires confirmation.
KEYWORDS:
alcohol intake; cohort; kidney cancer

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Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial.
SPRINT MIND Investigators for the SPRINT Research Group, Williamson JD, Pajewski NM, Auchus AP, Bryan RN, Chelune G, Cheung AK, Cleveland ML, Coker LH, Crowe MG, Cushman WC, Cutler JA, Davatzikos C, Desiderio L, Erus G, Fine LJ, Gaussoin SA, Harris D, Hsieh MK, Johnson KC, Kimmel PL, Tamura MK, Launer LJ, Lerner AJ, Lewis CE, Martindale-Adams J, Moy CS, Nasrallah IM, Nichols LO, Oparil S, Ogrocki PK, Rahman M, Rapp SR, Reboussin DM, Rocco MV, Sachs BC, Sink KM, Still CH, Supiano MA, Snyder JK, Wadley VG, Walker J, Weiner DE, Whelton PK, Wilson VM, Woolard N, Wright JT Jr, Wright CB.
JAMA. 2019 Jan 28. doi: 10.1001/jama.2018.21442. [Epub ahead of print]
PMID: 30688979
Abstract
IMPORTANCE:
There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia.
OBJECTIVE:
To evaluate the effect of intensive blood pressure control on risk of dementia.
DESIGN, SETTING, AND PARTICIPANTS:
Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke. Randomization began on November 8, 2010. The trial was stopped early for benefit on its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. The final date for follow-up of cognitive outcomes was July 22, 2018.
INTERVENTIONS:
Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683).
MAIN OUTCOMES AND MEASURES:
The primary cognitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia.
RESULTS:
Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cognitive assessment. The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio


, 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97).
CONCLUSIONS AND RELEVANCE:
Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point.

Single injection of rapamycin blocks post-food restriction hyperphagia and body-weight regain in rats.
Kenny TE, Hebert M, MacCallum P, Whiteman J, Martin GM, Blundell J.
Behav Neurosci. 2019 Feb;133(1):98-109. doi: 10.1037/bne0000287.
PMID: 30688487
Abstract
Given the increasing prevalence of and severity of complications associated with obesity, there is great need for treatments resulting in prolonged weight loss. Long-term maintenance of weight loss requires sustained changes in food-intake and energy-expenditure strategies, which are unfortunately often taxing, resulting in a return to predieting weight. Therefore, drug therapies may facilitate greater adherence to a restricted diet and prolong weight loss. One such drug is rapamycin (RAP), a mechanistic target of rapamycin (mTOR) inhibitor. Here, we show that a single injection of RAP dampens the hyperphagic response in calorically restricted rats when they are returned to free feed immediately or 10 days after injection. Moreover, we demonstrate that a single injection of RAP given to calorically restricted rats prevents body-weight regain when animals are returned to free feed either immediately or 10 days after injection. Furthermore, we extend our previous findings that RAP does not produce malaise or illness and show that RAP does not produce any behavioral deficits that may inhibit an animal from eating. Thus, we suggest that mTOR may be a useful target in obesity research, given that its inhibition may decrease the hyperphagic response following caloric restriction. 

Associations of Monounsaturated Fatty Acids from Plant and Animal Sources with Total and Cause-Specific Mortality in Two US Prospective Cohort Studies.
Guasch-Ferre M, Zong G, Willett WC, Zock P, Wanders AJ, Hu FB, Sun Q.
Circ Res. 2019 Jan 28. doi: 10.1161/CIRCRESAHA.118.313996. [Epub ahead of print]
PMID: 30689516
Abstract
RATIONALE:
Dietary monounsaturated fatty acids (MUFAs) can come from both plant and animal sources with divergent nutrient profiles that may potentially obscure the associations of total MUFAs with chronic diseases.
OBJECTIVE:
To investigate the associations of cis-MUFA intake from plant (MUFA-P) and animal (MUFA-A) sources with total and cause-specific mortality.
METHODS AND RESULTS:
We followed 63,412 women from the Nurses' Health Study (1990-2012) and 29,966 men from the Health Professionals Follow-Up Study (1990-2012). MUFA-Ps and MUFA-As were calculated based on data collected through validated food frequency questionnaires administered every 4-years and updated food composition databases. During 1,896,864 person-years of follow-up, 20,672 deaths occurred. Total MUFAs and MUFA-Ps were inversely associated with total mortality after adjusting for potential confounders, whereas MUFA-As were associated with higher mortality. When MUFA-Ps were modeled to iso-calorically replace other macronutrients, hazard ratios [HRs, 95% confidence intervals (95%CIs)] of total mortality were 0.84 (0.77, 0.92;P<0.001) for replacing saturated fatty acids (SFAs; 5% of energy); 0.86 (0.82, 0.91;P<0.001) for replacing refined carbohydrates (5% energy); 0.91 (0.85, 0.97;P<0.001) for replacing trans fats (2% energy), and 0.77 (0.71, 0.82; P<0.001) for replacing MUFA-As (5% energy). For iso-calorically replacing MUFA-As with MUFA-Ps, HRs (95% CIs) were 0.74 (0.64, 0.86; P<0.001) for cardiovascular mortality; 0.73 (0.65, 0.82; P<0.001) for cancer mortality, and 0.82 (0.73, 0.91; P<0.001) for mortality due to other causes.
CONCLUSIONS:
Higher intake of MUFA-Ps was associated with lower total mortality, and MUFA-As intake was associated with higher mortality. Significantly lower mortality risk was observed when SFAs, refined carbohydrates, or trans fats were replaced by MUFA-Ps, but not MUFA-As. These data suggest that other constituents in animal foods, such as SFAs, may confound the associations for MUFAs when they are primarily derived from animal products. More evidence is needed to elucidate the differential associations of MUFA-Ps and MUFA-As with mortality.
KEYWORDS:
animal fat; cause-specific mortality; monounsaturated fatty acids; plant fat

Association between Serum Selenium Level and the Presence of Diabetes Mellitus: A Meta-Analysis of Observational Studies.
Kim J, Chung HS, Choi MK, Roh YK, Yoo HJ, Park JH, Kim DS, Yu JM, Moon S.
Diabetes Metab J. 2019 Jan 2. doi: 10.4093/dmj.2018.0123. [Epub ahead of print]
PMID: 30688047
https://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-43-e1.pdf
Abstract
BACKGROUND:
Epidemiological studies have suggested an association between selenium (Se) and diabetes mellitus (DM). However, different studies have reported conflicting results. Therefore, we performed a comprehensive meta-analysis to clarify the impact of Se on DM.
METHODS:
We searched the PubMed database for studies on the association between Se and DM from inception to June 2018.
RESULTS:
Twenty articles evaluating 47,930 participants were included in the analysis. The meta-analysis found that high levels of Se were significantly associated with the presence of DM (pooled odds ratios [ORs], 1.88; 95% confidence interval [CI], 1.44 to 2.45). However, significant heterogeneity was found (I²=82%). Subgroup analyses were performed based on the Se measurement methods used in each study. A significant association was found between high Se levels and the presence of DM in the studies that used blood (OR, 2.17; 95% CI, 1.60 to 2.93; I²=77%), diet (OR, 1.61; 95% CI, 1.10 to 2.36; I²=0%), and urine (OR, 1.49; 95% CI, 1.02 to 2.17; I²=0%) as samples to estimate Se levels, but not in studies on nails (OR, 1.24; 95% CI, 0.52 to 2.98; I²=91%). Because of significant heterogeneity in the studies with blood, we conducted a sensitivity analysis and tested the publication bias. The results were consistent after adjustment based on the sensitivity analysis as well as the trim and fill analysis for publication bias.
CONCLUSION:
This meta-analysis demonstrates that high levels of Se are associated with the presence of DM. Further prospective and randomized controlled trials are warranted to elucidate the link better.
KEYWORDS:
Antioxidants; Diabetes mellitus; Selenium; Trace elements

Diet and risk of glioma: combined analysis of three large prospective studies in the UK and USA.
Kuan AS, Green J, Kitahara CM, Berrington de González A, Key T, Reeves G, Floud S, Balkwill A, Bradbury K, Liao LM, Freedman ND, Beral V, Sweetland S; collaborators of the Million Women Study; NIH-AARP Study; PLCO Study.
Neuro Oncol. 2019 Jan 23. doi: 10.1093/neuonc/noz013. [Epub ahead of print]
PMID: 30690490
Abstract
BACKGROUND:
Available evidence on diet and glioma risk comes mainly from studies with retrospective collection of dietary data. To minimise possible differential dietary recall between those with and without glioma, we present findings from three large prospective studies.
METHODS:
Participants included 692,176 from (UK) Million Women Study, 470,780 from (US) NIH-AARP Study, and 99,148 from (US) PLCO Study. Cox regression yielded study-specific adjusted relative risks for glioma in relation to 15 food groups, 14 nutrients, and 3 dietary patterns, which were combined, weighted by inverse-variances of the relative risks. Separate analyses by <5 and ≥5 years follow-up assessed potential biases related to changes of diet before glioma diagnosis.
RESULTS:
The 1,262,104 participants, mean age 60.6 (SD5.5) at baseline, were followed for 15.4 million person-years (mean 12.2 years/participant), during which 2,313 incident gliomas occurred, at mean age 68.2 (SD6.4). Overall, there was weak evidence for increased glioma risks associated with increasing intakes of total fruit, citrus fruit, and fibre, and healthy dietary patterns, but these associations were generally null after excluding the first 5 years of follow-up. There was little evidence for heterogeneity of results by study or by sex.
CONCLUSIONS:
The largest prospective evidence to date suggests little, if any, association between major food groups, nutrients, or common healthy dietary patterns, and glioma incidence. With the statistical power of this study and the comprehensive nature of the investigation here, it seems unlikely we have overlooked major effects of diet on risk of glioma that would be of public health concern.

Serum Sex Hormones and the Risk of Fracture across the Menopausal Transition: Study of Women's Health Across the Nation.
Cauley JA, Ruppert K, Lian Y, Finkelstein JS, Karvonen-Gutierrez CA, Harlow SD, Lo JC, Burnett-Bowie SM, Karlamangla A, Greendale GA.
J Clin Endocrinol Metab. 2019 Jan 23. doi: 10.1210/jc.2018-02047. [Epub ahead of print]
PMID: 30690517
Abstract
CONTEXT:
Sex steroid hormones have been linked to fractures in older women.
OBJECTIVE:
To test the hypothesis that hormones measured over the menopausal transition predict fractures.
SETTING:
7 US clinical centers.
SUBJECTS AND MEASUREMENTS:
2960 women (average age 46.4 ± 2.7 years) who had at least two repeat hormone measures and prospective information on fractures. Fasting serum was collected annually for hormone assays. Estradiol (E2) was measured with a modified direct immunoassay. Follicle-stimulating hormone (FSH) and sex hormone binding globulin (SHBG) were measured with 2 site chemiluminescence immunoassays. Hormones were lagged (visit year -1) and transformed using log base 2. Incident fractures were ascertained at each annual visit. All medications including hormone therapy (HT) were time varying covariates. Discrete survival methods were used.
RESULTS:
508 (17.1%) women experienced an incident fracture over an average follow-up of 8.8 ± 4.4 years. Women who experienced an incident fracture were more likely to be White, report high alcohol intake and diabetes and less likely to report premenopausal status at baseline. A woman whose log E2 was twice that of another had a 10% lower risk of fracture independent of covariates, relative risk (95% confidence intervals) = 0.90 (0.82, 0.98). Neither FSH or SHBG were associated with fractures.
CONCLUSIONS:
Serum E2 levels may help to identify women at higher risk of fractures over the menopausal transition. However, hormone assays must be standardized across laboratories for clinical implementation and further work is needed to define E2 thresholds.

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Analysis of the Association Between TERC and TERT Genetic Variation and Leukocyte Telomere Length and Human Lifespan-A Follow-Up Study.
Scarabino D, Peconi M, Pelliccia F, Corbo RM.
Genes (Basel). 2019 Jan 25;10(2). pii: E82. doi: 10.3390/genes10020082.
PMID: 30691026
[See https://www.mdpi.com/2073-4425/10/2/82 for pdf.]
Abstract
We investigated the possible influence of TERC and TERT genetic variation and leukocyte telomere length (LTL) on human lifespan. Four polymorphisms of TERT and three polymorphisms of TERC were examined in a sample of elderly subjects (70⁻100 years). After nine years of follow-up, mortality data were collected, and sub-samples of long-lived/not long-lived were defined. TERT VNTR MNS16A L/L genotype and TERT rs2853691 A/G or G/G genotypes were found to be associated with a significantly higher risk to die before the age of 90 years, and with a significantly lower age at death. The association between lifespan and LTL at baseline was analyzed in a subsample of 163 subjects. Age at baseline was inversely associated with LTL (p < 0.0001). Mean LTL was greater in the subjects still living than in those no longer living at follow-up (0.79 T/S ± 0.09 vs 0.63 T/S ± 0.08, p < 0.0001). Comparison of age classes showed that, among the 70⁻79-year-olds, the difference in mean LTL between those still living and those no longer living at follow-up was greater than among the 80⁻90-year-olds. Our data provide evidence that shorter LTL at baseline may predict a shorter lifespan, but the reliability of LTL as a lifespan biomarker seems to be limited to a specific age (70⁻79 years).
KEYWORDS:
TERC; TERT; genetic variation; human lifespan; leukocyte telomere length

Frailty, transition in frailty status and all-cause mortality in older adults of a Taichung community-based population.
Wang MC, Li TC, Li CI, Liu CS, Lin WY, Lin CH, Yang CW, Yang SY, Lin CC.
BMC Geriatr. 2019 Jan 28;19(1):26. doi: 10.1186/s12877-019-1039-9.
PMID: 30691410
Abstract
BACKGROUND:
Previous studies have reported the associations of frailty phenotype or its components with mortality. However, studies that explored the effects of transition in frailty status on mortality were far less in Asian or Chinese. The aim of this study was to evaluate baseline frailty status and one-year change of frailty status in relation to all-cause mortality in Taiwanese community-dwelling older adults who participated in the Taichung Community Health Study for Elders.
METHODS:
We conducted a community-based prospective cohort study. A total of 921 community-dwelling elderly men and women aged 65-99 years in Taichung City were enrolled in 2009-2010 and were followed up through 2016. We adopted the definition of frailty proposed by Fried et al., including five components: shrinking, weakness, poor endurance and energy, slowness, and low physical activity. Cox proportional hazards models were used to determine adjusted hazard ratios (HRs) of mortality with 95% confidence intervals (CIs) for frailty at baseline and one-year change in frailty status.
RESULTS:
There were 160 deaths during the follow-up period. The mortality rates in groups of robust and frail were 20.26 and 84.66 per 1000 person-years respectively. After multivariate adjustment, the HR (CIs) for baseline frailty was 2.67 (1.73-4.12). Poor endurance and energy [1.88 (1.03-3.42)], slowness [2.60 (1.76-3.83)] and weakness [1.65 (1.16-2.33)] were found to be predictors of mortality. Increased risks in mortality for subgroups of robust-to-frail [2.76 (1.22-6.27)], frail-to-robust [3.87 (1.63, 9.19)], and frail-to-frail [4.08 (1.92-8.66)] over one-year period were observed compared with those remaining robust.
CONCLUSION:
Baseline frailty status and one-year change in frailty status are associated with 6-year all-cause mortality among Taiwanese elderly adults. Frailty may be useful for identifying older adults at high risks for mortality prevention.

Protein timing has no effect on lean mass, strength and functional capacity gains induced by resistance exercise in postmenopausal women: A randomized clinical trial.
de Branco FMS, Carneiro MAS, Rossato LT, Nahas PC, Teixeira KRC, de Oliveira GN Jr, Orsatti FL, de Oliveira EP.
Clin Nutr. 2019 Jan 17. pii: S0261-5614(19)30010-X. doi: 10.1016/j.clnu.2019.01.008. [Epub ahead of print]
PMID: 30691866
Abstract
BACKGROUND & AIMS:
Short-term studies have shown that protein intake immediately post-exercise increases muscle protein synthesis. However, the effect of protein timing (comparing protein intake post-exercise vs. several hours after exercise) on lean mass and strength gains in long-term studies is still not fully elucidated. Thus, the aim of our study was to evaluate the effect of protein timing on lean mass, strength and functional capacity gains induced by resistance exercise in postmenopausal women.
METHODS:
Thirty-four postmenopausal women (60.9 ± 6.7 years) participated in this double-blind, parallel-group, randomized clinical trial. All individuals performed the same resistance training protocol in the morning, 3 times a week, at 70% of 1-maximum repetition (1-RM), over 8 weeks. Participants were randomly assigned to protein-carbohydrate group (PC) (n = 17), that ingested 30 g of whey protein immediately after exercise and 30 g of maltodextrin in the afternoon; and to carbohydrate-protein group (CP) (n = 17), that ingested 30 g of maltodextrin immediately after exercise and 30 g of whey protein in the afternoon. Lean mass was assessed using dual-energy X-ray absorptiometry, handgrip strength by a dynamometer, and strength was evaluated by 1-RM of bench press and leg extension. One mile walk test was performed to assess the functional capacity.
RESULTS:
Both the PC group (37.3 [35.0-39.7] to 38.1 [35.9-40.5] kg) and the CP group (38.2 [36.0-40.5] to 38.8 [36.5-41.3] kg) increased the total lean mass (p < 0.001). An increase was also observed in both groups for 1-RM bench press, 1-RM leg extension and handgrip strength (p < 0.001). In addition, the time of 1-mile walk test decreased in both groups (p = 0.019). No differences were noted for group and time interaction for these variables (p > 0.05).
CONCLUSION:
Protein timing has no effect on lean mass, strength and functional capacity gains induced by resistance exercise in postmenopausal women. This trial was registered at ClinicalTrials.gov as NCT03372876.
KEYWORDS:
Anabolic window; Body composition; Muscle mass gain; Older adults; Protein timing

B-vitamins in Relation to Depression in Older Adults Over 60 Years of Age: The Trinity Ulster Department of Agriculture (TUDA) Cohort Study.
Moore K, Hughes CF, Hoey L, Ward M, Cunningham C, Molloy AM, Strain JJ, McCarroll K, Casey MC, Tracey F, Laird E, O'Kane M, McNulty H.
J Am Med Dir Assoc. 2019 Jan 25. pii: S1525-8610(18)30699-6. doi: 10.1016/j.jamda.2018.11.031. [Epub ahead of print]
PMID: 30692033
Abstract
OBJECTIVES:
Mental health disorders are major contributors to disease burden in older people. Deficient status of folate and the metabolically related B vitamins may be implicated in these conditions. This study aimed to investigate folate, vitamin B12, vitamin B6, and riboflavin in relation to depression and anxiety in aging and also considered the role of fortified foods as a means of optimizing B-vitamin status and potentially reducing the risk of these mental health disorders.
DESIGN:
The Trinity Ulster Department of Agriculture (TUDA) aging study was a cross-sectional cohort study.
SETTING AND PARTICIPANTS:
Community-dwelling adults (n = 5186; ≥60 years) recruited from 2 jurisdictions within the island of Ireland from 2008 to 2012.
MEASURES:
Depression and anxiety were assessed using the Centre for Epidemiological Studies Depression (CES-D) and the Hospital Anxiety and Depression (HAD) scales, respectively. The following B-vitamin biomarkers were measured: red blood cell folate, serum total vitamin B12, plasma pyridoxal-5-phosphate (PLP; vitamin B6), and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin).
RESULTS:
Biomarker values in the lowest 20% of status for folate (odds ratio [OR] 1.79; 95% CI 1.23-2.61), vitamin B6 (OR 1.45, 95% CI 1.01-2.06), or riboflavin (OR 1.56, 95% CI 1.10-2.00), but not vitamin B12, were each associated with an increased risk of depression (CES-D score ≥16). Correspondingly, B vitamin-fortified foods if consumed daily were associated with a reduced risk of depression (OR 0.54, 95% CI 0.41-0.70). A deficient status of vitamin B6 (OR 1.73, 95% CI 1.07-2.81), but not other vitamins, was associated with increased anxiety.
CONCLUSIONS/IMPLICATIONS:
Better B-vitamin status may have a role in impacting positively on mental health in older adults. Regular intake of fortified foods can provide a means of optimizing B-vitamin status and thus could contribute to reducing depression. If confirmed by a randomized trial, these results may have implications for nutrition and mental health policy, and thus quality of life, in older people.
KEYWORDS:
B vitamins; aging; anxiety; depression; folate; food fortification

Adiposity in relation to risks of fatty liver, cirrhosis and liver cancer: a prospective study of 0.5 million Chinese adults.
Pang Y, Kartsonaki C, Turnbull I, Guo Y, Chen Y, Clarke R, Bian Z, Bragg F, Millwood IY, Yang L, Huang Y, Yang Y, Zhang X, Chen J, Li L, Holmes MV, Chen Z.
Sci Rep. 2019 Jan 28;9(1):785. doi: 10.1038/s41598-018-36460-7.
PMID: 30692555
https://www.nature.com/articles/s41598-018-36460-7.pdf
Abstract
Adiposity is an increasing public health problem in China. We aimed to examine the associations of adiposity with non-alcoholic fatty liver disease (NAFLD) and other chronic liver diseases in Chinese adults. The prospective China Kadoorie Biobank recruited 512,891 adults aged 30-79 years from 10 areas. During 10 years of follow-up, 7,386 incident liver disease cases were recorded among 503,991 participants without prior cancer or chronic liver disease at baseline. The mean body mass index (BMI) (SD) was 23.7 (3.3) kg/m2 and mean waist circumference (WC) 80.3 (9.8) cm, with 33% having BMI ≥25 kg/m2. Throughout the range examined (BMI 15-50) BMI showed a log-linear positive association with NAFLD (n = 1,298), with adjusted HR per 5 kg/m2 of 2.81 (95% CI 2.63-3.01), adjusting for regression dilution. There were also positive associations of percent body fat, WC, and waist-to-hip ratio with NAFLD, with HRs per 1-SD of 2.27 (2.14-2.41), 2.60 (2.44-2.76), and 1.84 (1.76-1.92). BMI was unrelated to viral hepatitis (n = 1,477), and had a U-shaped association with cirrhosis (n = 2,082) and an inverse association with liver cancer (n = 2,568), which disappeared after excluding the first 5 years of follow-up. Among Chinese adults, adiposity was a major risk factor for NAFLD but not other chronic liver diseases.

Total nut, tree nut, peanut, and peanut butter intake and the risk of prostate cancer in the Netherlands Cohort Study.
Boudewijns EA, Nieuwenhuis L, Geybels MS, van den Brandt PA.
Prostate Cancer Prostatic Dis. 2019 Jan 28. doi: 10.1038/s41391-019-0131-8. [Epub ahead of print]
PMID: 30692586
https://sci-hub.tw/10.1038/s41391-019-0131-8
Abstract
BACKGROUND:
The consumption of nuts has been associated with a reduction of cancer risk, but only a few studies have examined the effects of nuts on prostate cancer risk. The current study prospectively investigated the association between the consumption of total nuts, tree nuts, peanuts, and peanut butter and the risk of total, advanced, and non-advanced prostate cancer.
METHODS:
The association between nuts and prostate cancer was evaluated in the Netherlands Cohort Study, which was conducted among 58,279 men aged 55-69 year at baseline. A case-cohort approach was used for data processing and analyses. After 20.3 years of follow-up, 3868 incident prostate cancer cases and 1979 subcohort members were available for multivariable Cox regression analyses.
RESULTS:
For total, advanced, and non-advanced prostate cancer, no significant associations were found for total nuts (total prostate cancer: hazard ratio (HR) (95%CI) for 10+ g/day vs. non-consumers = 1.09 (0.92-1.29), Ptrend = 0.409). No significant associations were observed for tree nuts and peanuts for total, advanced, and non-advanced prostate cancer risk. Peanut butter consumption was associated with a significantly increased risk of non-advanced prostate cancer (HR (95%CI) for 5+ g/day vs. non-consumers = 1.33 (1.08-1.63), Ptrend = 0.008), but not with total or advanced prostate cancer.
CONCLUSIONS:
No significant associations were found between total nut, tree nut, and peanut consumption and total, advanced, and non-advanced prostate cancer. Peanut butter might be associated with an increased non-advanced prostate cancer risk.

Fiber Intake and the Risk of Head and Neck Cancer in the prostate, lung, colorectal, and ovarian (PLCO) cohort.
Kawakita D, Lee YA, Gren LH, Buys SS, La Vecchia C, Hashibe M.
Int J Cancer. 2019 Jan 29. doi: 10.1002/ijc.32162. [Epub ahead of print]
PMID: 30693489
Abstract
Although the protective role of dietary fiber on cancer risk has been reported in several epidemiological studies, the association of fiber intake on head and neck cancer (HNC) risk is still unclear. We investigated the association between fiber intake and the risk of HNC using data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. Among 101,700 participants with complete dietary information, 186 participants developed HNC during follow-up (January 1998 to May 2011). Dietary data were collected using a self-administered food-frequency questionnaire (1998-2005). We estimated hazard ratios (HRs) and the corresponding 95% confidence intervals (CI), using the Cox proportional hazards model. Higher intake of total fiber, insoluble fiber and soluble fiber was associated with decreased HNC risks, with a significant trend. The HRs of highest versus the lowest tertile of intake were 0.43 (95%CI: 0.25-0.76) for total fiber, 0.38 (95%CI: 0.22-0.65) for insoluble fiber, and 0.44 (95%CI: 0.25-0.79) for soluble fiber. These inverse association were consistent in oral cavity and pharyngeal cases, but the impact of fiber intake was weaker in laryngeal cases. We did not observe any significant interaction of potential confounders, including smoking and drinking, with total fiber intake on HNC risk. These findings support evidence of a protective role of dietary fiber on HNC risk.
KEYWORDS:
Dietary fiber; Head and Neck Cancer; Insoluble fiber; Prospective Cohort Study; Soluble fiber

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Evidence that Jeanne Calment died in 1934, not 1997.
Zak N.
Rejuvenation Res. 2019 Jan 30. doi: 10.1089/rej.2018.2167. [Epub ahead of print]
PMID: 30696353
Abstract
I present a body of data that, I argue, cumulatively casts serious doubt on the validity of Jeanne Calment's accepted world record of human lifespan. First, I assess the plausibility of the record based on the lifespans of other centenarians in the International Database of Longevity (IDL) and critique some arguments put forward previously in support of this record, including the longevity of Calment's ancestors. Second, I review the literature dedicated to Calment and discuss multiple contradictions in her interviews, biographies, photos, and documents. I argue that the evidence from these sources motivates renewed consideration of the previously rejected hypothesis that Jeanne's daughter Yvonne acquired her mother's identity after her death in order to avoid paying inheritance tax and that Jeanne Calment's death was reported as Yvonne's death in 1934. Finally I discuss the importance of reconsidering the principles of validation, due to the possibility of similar problems regarding other exceptionally long-lived people and the mistaken inferences that researchers may draw from flawed datasets. The phenomenon of Jeanne Calment may prove to be an instructive example of the uncertainty of seemingly well-established facts.

Validated Living Worldwide Supercentenarians 112+, Living and Recently Deceased: February 2019.
Young RD, Kroczek WJ.
Rejuvenation Res. 2019 Jan 30. doi: 10.1089/rej.2019.2179. [Epub ahead of print]
PMID: 30696356
Abstract
By definition, a validated supercentenarian is a properly documented centenarian who has lived to be at least the age of 110 years. The tables presented here, based on records maintained by members of the Gerontology Research Group (GRG), continue the series published in Rejuvenation Research in past years1,2 - giving the latest list of living supercentenarians, currently with a cutoff age of 112+. It should be emphasized that this list cannot include all living supercentenarians, only those whose claim can be validated to the required standard bsed on information available to us; we estimate the true population worldwide to be in the range 600-900. For more details, or to submit a claim, please contact us at www.grg.org. As of January 24, 2019, there were 35 living supercentenarians on our list (all females).

Growth differentiation factor-15 and the risk of cardiovascular diseases and all-cause mortality: A Meta-analysis of Prospective Studies.
Xie S, Lu L, Liu L.
Clin Cardiol. 2019 Jan 29. doi: 10.1002/clc.23159. [Epub ahead of print]
PMID: 30697778
Abstract
BACKGROUND AND AIM:
Previous studies have documented that the association between growth differentiation factor-15(GDF-15) the risk of patients with cardiovascular diseases. In this meta-analysis, our main objective is to explore the associations between growth differentiation factor-15 and the risk of cardiovascular diseases (CVD) or all-cause mortality.
METHODS:
PubMed and ISI Web of Science (up to January 2018) electronic databases were browsed for eligible studies. The studies provided relevant data depicted as hazard ratio (HR) with 95% confidence interval (CI), with regard to the association between GDF-15 levels and subsequent risk of cardiovascular diseases or all-cause mortality. A random-effect model was applied to pool the HR and 95% CI.
RESULTS:
Thirty-one prospective studies met the eligibility criteria involving 53706 subjects with 7020 adverse outcome events. It was concluded that GDF-15 levels were associated with an incremental risk of cardiovascular diseases or all-cause mortality. Highest GDF-15 category was associated with greater risk of cardiovascular mortality (HR, 2.66;95% CI, 1.69 -3.63), all-cause mortality (HR, 2.52; 95% CI, 2.06 -2.97), and complex adverse outcome (HR, 1.81; 95% CI, 1.42 - 2.21) .As each log-unit increment in GDF-15 concentration ,the corresponding risk of adverse events also escalated, cardiovascular mortality (HR, 2.11 ; 95% CI, 1.57 -2.66), all-cause mortality (HR, 2.70; 95% CI, 2.29 - 3.12), and complex adverse outcome (HR, 1.96; 95% CI, 1.64 - 2.29).
CONCLUSIONS:
Judging from the results of the data analysis, GDF-15 levels may increase the risk of cardiovascular diseases or all-cause mortality.
KEYWORDS:
All-cause mortality; Cardiovascular diseases; Growth differentiation factor-15; Meta-analysis

Association of All-Cause and Cardiovascular Mortality With High Levels of Physical Activity and Concurrent Coronary Artery Calcification.
DeFina LF, Radford NB, Barlow CE, Willis BL, Leonard D, Haskell WL, Farrell SW, Pavlovic A, Abel K, Berry JD, Khera A, Levine BD.
JAMA Cardiol. 2019 Jan 30. doi: 10.1001/jamacardio.2018.4628. [Epub ahead of print]
PMID: 30698608
Abstract
IMPORTANCE:
Few data are available to guide clinical recommendations for individuals with high levels of physical activity in the presence of clinically significant coronary artery calcification (CAC).
OBJECTIVE:
To assess the association among high levels of physical activity, prevalent CAC, and subsequent mortality risk.
DESIGN, SETTING, AND PARTICIPANTS:
The Cooper Center Longitudinal Study is a prospective observational study of patients from the Cooper Clinic, a preventive medicine facility. The present study included participants seen from January 13, 1998, through December 30, 2013, with mortality follow-up through December 31, 2014. A total of 21 758 generally healthy men without prevalent cardiovascular disease (CVD) were included if they reported their physical activity level and underwent CAC scanning. Data were analyzed from September 26, 2017, through May 2, 2018.
EXPOSURES:
Self-reported physical activity was categorized into at least 3000 (n = 1561), 1500 to 2999 (n = 3750), and less than 1500 (n = 16 447) metabolic equivalent of task (MET)-minutes/week (min/wk). The CAC scores were categorized into at least 100 (n = 5314) and less than 100 (n = 16 444) Agatston units (AU).
MAIN OUTCOMES AND MEASURES:
All-cause and CVD mortality collected from the National Death Index Plus.
RESULTS:
Among the 21 758 male participants, baseline mean (SD) age was 51.7 (8.4) years. Men with at least 3000 MET-min/wk were more likely to have prevalent CAC of at least 100 AU (relative risk, 1.11; 95% CI, 1.03-1.20) compared with those accumulating less physical activity. In the group with physical activity of at least 3000 MET-min/wk and CAC of at least 100 AU, mean (SD) CAC level was 807 (1120) AU. After a mean (SD) follow-up of 10.4 (4.3) years, 759 all-cause and 180 CVD deaths occurred, including 40 all-cause and 10 CVD deaths among those with physical activity of at least 3000 MET-min/wk. Men with CAC of less than 100 AU and physical activity of at least 3000 MET-min/wk were about half as likely to die compared with men with less than 1500 MET-min/wk (hazard ratio {HR}, 0.52; 95% CI, 0.29-0.91). In the group with CAC of at least 100 AU, men with at least 3000 MET-min/wk did not have a significant increase in all-cause mortality (HR, 0.77; 95% CI, 0.52-1.15) when compared with men with physical activity of less than 1500 MET-min/wk. In the least active men, those with CAC of at least 100 AU were twice as likely to die of CVD compared with those with CAC of less than 100 AU (HR, 1.93; 95% CI, 1.34-2.78).

CONCLUSIONS AND RELEVANCE:
This study suggests there is evidence that high levels of physical activity (≥3000 MET-min/wk) are associated with prevalent CAC but are not associated with increased all-cause or CVD mortality after a decade of follow-up, even in the presence of clinically significant CAC levels.

Dairy Product Intake and Cardiometabolic Diseases in Northern Sweden: A 33-Year Prospective Cohort Study.
Johansson I, Esberg A, Nilsson LM, Jansson JH, Wennberg P, Winkvist A.
Nutrients. 2019 Jan 28;11(2). pii: E284. doi: 10.3390/nu11020284.
PMID: 30696081
[pdf availed from https://www.mdpi.com/2072-6643/11/2/284 site.]
Abstract
Dairy products are important constituents of most diets, and their association with adverse health outcomes remains a focus. We characterized dairy food intake and examined associations with the incidence of type 2 diabetes (T2D), myocardial infarction (MI) or stroke among 108,065 Swedish men and women. Hazard ratios (HRs) and 95% CIs were estimated using the multivariable Cox proportional hazards models in a population characterized by high milk tolerance. During a mean follow-up of 14.2 years, 11,641 first-time events occurred. Non-fermented milk intake decreased, whereas butter intake increased over the period. For high intake of non-fermented milk, the HR (95% CI) for developing T2D and MI was 1.17 (1.03, 1.34) and 1.23 (1.10, 1.37), respectively, in men. A greater intake of butter, fermented milk, and cheese tended to be associated with a reduced risk of T2D and/or MI. Non-consumers and those who chose low-fat variants of the targeted dairy products had increased risk for T2D, MI, or stroke compared to those in the non-case group. Generally, effect-sizes were small. This prospective study found that non-fermented milk was associated with an increased risk for developing T2D and MI and that subjects abstaining from dairy products or choosing low-fat variants were at greater risk. However, the overall cardiometabolic risk of non-fermented milk intake was judged as low, since the effect sizes were small.
KEYWORDS:
cardiovascular disease; dairy products; milk; myocardial infarction; stroke; type 2 diabetes

A Prospective Association of Nut Consumption with Cognitive Function in Chinese Adults aged 55+ _ China Health and Nutrition Survey.
Li M, Shi Z.
J Nutr Health Aging. 2019;23(2):211-216. doi: 10.1007/s12603-018-1122-5.
PMID: 30697633
Abstract
OBJECTIVES:
We aimed to investigate the association of nut intake with cognitive function in Chinese adults aged 55 and over.
DESIGN:
This was a prospective open cohort study with repeated measurements of diet and cognition scores. Participants/settings: 4822 adults aged 55 and over participating in the China Health Nutrition Survey during 1991-2006.
MEASUREMENTS:
Global cognitive function measured repeatedly in 1997, 2001, 2004, and 2006 using a subset of modified Telephone Interview for Cognitive Status; poor cognitive function was defined as cognition score<7. Nut consumption was collected using 3-day 24 recall method in 1991, 1993, and at surveys of cognition assessment.
STATISTICAL ANALYSES PERFORMED:
Multilevel mixed effect linear regression and logistic regression analysis were conducted to assess the association with cognitive function.
RESULTS:
The unadjusted cognitive score decreased by 0.29 (95% CI 0.22-0.28) with one-year aging during 1997-2006. Nut intake of more than 10g/d was associated with higher cognition score by 0.63 points (95% CI 0.15-1.12) or 40% less likely to have poor cognitive function (OR 0.60, 95% CI 0.43-0.84) after adjusted for demographic, lifestyle behavioural, BMI, and energy intake.
CONCLUSIONS:
Nut consumption was inversely associated with cognition decline.
KEYWORDS:
China Nutrition and Health Survey; Nut consumption; cognition function; prospective association

Edited by AlPater

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Intestinal permeability after Mediterranean diet and low-fat diet in non-alcoholic fatty liver disease.
Biolato M, Manca F, Marrone G, Cefalo C, Racco S, Miggiano GA, Valenza V, Gasbarrini A, Miele L, Grieco A.
World J Gastroenterol. 2019 Jan 28;25(4):509-520. doi: 10.3748/wjg.v25.i4.509.
PMID: 30700946
https://www.wjgnet.com/1007-9327/full/v25/i4/509.htm
Abstract
BACKGROUND:
In non-alcoholic fatty liver disease (NAFLD), a high-fat or high-fructose diet increases intestinal permeability and promotes derangement of the gut-liver axis. We hypothesize that, diet could be able to modulate intestinal permeability in patients with NAFLD.
AIM:
To detect diet-induced modification of intestinal permeability in patients with NAFLD undergoing a Mediterranean diet or a low-fat diet.
METHODS:
The current study was a dietary intervention for non-diabetic, patients with biopsy-verified NAFLD and increased transaminases. A crossover design was employed: participants underwent 16 weeks of Mediterranean diet, 16 wk of free wash-out, and 16 weeks of low-fat diet. Both diets were hypocaloric and no consumption of supplements was allowed. All patients were followed bimonthly by a dietitian. Evaluations of clinical and metabolic parameters were completed at baseline and at the end of each dietary period. Intestinal permeability was assessed by chromium-51 ethylene diamine tetraacetate excretion testing (51Cr-EDTA).
RESULTS:
Twenty Caucasian patients, 90% male, median age 43 years, body mass index (BMI) 30.9, with biopsy-verified NAFLD were enrolled. At the end of 16 weeks of a Mediterranean diet, a significant reduction in mean body weight (-5.3 ± 4.1 kg, P = 0.003), mean waist circumference (-7.9 ± 4.9 cm, P = 0.001), and mean transaminase levels [alanine aminotransferase (ALT) -28.3 ± 11.9 IU/L, P = 0.0001; aspartate aminotransferase (AST) -6.4 ± 56.3 IU/L, P = 0.01] were observed. These benefits were maintained after 16 wk of wash-out and also after 16 wk of low-fat diet, without further improvements. Fourteen of the 20 patients had intestinal permeability alteration at baseline (mean percentage retention of 51Cr-EDTA = 5.4%), but no significant changes in intestinal permeability were observed at the end of the 16 wk of the Mediterranean diet or 16 wk of the low-fat diet.
CONCLUSION:
Mediterranean diet is an effective strategy for treating overweight, visceral obesity and serum transaminase in patients with NAFLD. If the Mediterranean diet can improve intestinal permeability in patients with NAFLD, it deserves further investigation.
KEYWORDS:
Gut-liver axis; Liver steatosis; Nutrition; Personalized medicine; Visceral obesity

[I always thought that the difference beteen the experimental and placebo data were the important thing.]
Blueberries Improve Pain, Gait Performance, and Inflammation in Individuals with Symptomatic Knee Osteoarthritis.
Du C, Smith A, Avalos M, South S, Crabtree K, Wang W, Kwon YH, Vijayagopal P, Juma S.
Nutrients. 2019 Jan 29;11(2). pii: E290. doi: 10.3390/nu11020290.
PMID: 30699971
https://www.mdpi.com/2072-6643/11/2/290/htm
Abstract
Osteoarthritis (OA) is the most common joint disorder in the world and is the most frequent cause of walking related disability among older adults in the US, which brings a significant economic burden and reduces quality of life. The initiation and development of OA typically involves degeneration or progressive loss of the structure and function of articular cartilage. Inflammation is one of the major drives of the progression of OA. Dietary polyphenols have been studied for their anti-inflammatory properties and potential anabolic effects on the cartilage cells. Blueberries are widely consumed and are high in dietary polyphenols, therefore regular consumption of blueberries may help improve OA. The purpose of the present study was to examine the effect of freeze dried whole blueberries on pain, gait performance, and inflammation in individuals with symptomatic knee OA. In a randomized, double-blind trial, adults age 45 to 79 with symptomatic knee OA, were randomized to either consume 40 g freeze-dried blueberry powder (n = 33) or placebo powder (n = 30) daily for four months. Blood draws and assessment of pain and gait were conducted at baseline, two months, and four months. Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaires were used to assess pain and GAITRite® electronic walkway was used to evaluate gait spatiotemporal parameters. WOMAC total score and sub-groups, including pain, stiffness, and difficulty to perform daily activities decreased significantly in the blueberry treatment group (p < 0.05), but improvement of WOMAC total score and difficulty to perform daily activities were not observed in the placebo group. Normal walking pace single support percentage for both limbs increased (p = or < 0.007), while double support percentage for both limbs decreased in the blueberry treatment group (p = or < 0.003). No significant changes were observed in plasma concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-10, IL-13, matrix metalloproteinases (MMP)-3, MMP-13, and monocyte chemoattractant protein-1 (MCP-1) in both treatment groups. However, an increasing trend for IL-13 concentration and a decreasing trend in MCP-1 concentration were noted in the blueberry group. The findings of this study suggest that daily incorporation of whole blueberries may reduce pain, stiffness, and difficulty to perform daily activities, while improving gait performance, and would therefore improve quality of life in individuals with symptomatic knee OA.
KEYWORDS:
blueberry; gait; inflammation; knee osteoarthritis; pain; polyphenols

Body mass index and risk of intestinal metaplasia: A cohort study.
Ryu S, Kim K, Chang Y, Ahn J, Yang HJ, Jung JY, Kim S, Sohn CI.
Cancer Epidemiol Biomarkers Prev. 2019 Jan 30. pii: cebp.0733.2018. doi: 10.1158/1055-9965.EPI-18-0733. [Epub ahead of print]
PMID: 30700447
Abstract
BACKGROUND:
We examined the association between body mass index (BMI) and development of endoscopic intestinal metaplasia (IM).
METHODS:
This retrospective cohort study included 142,832 Korean adults free of endoscopic IM and atrophic gastritis (AG) who underwent upper endoscopy at baseline and subsequent visits and were followed for up to 5 years. A parametric proportional hazards model was used to estimate the adjusted hazard ratio with 95% confidence interval (CI) for incident IM.
RESULTS:
Over 444,719.1 person-years of follow-up, 2281 participants developed endoscopic IM (incidence rate, 5.1 per 1,000 person-years). Increased BMI categories were associated with increased risk of new-onset IM in a dose-response manner. After adjustment for age, sex, center, year of screening exam, smoking status, alcohol intake, exercise, total calorie intake, history of diabetes and hypertension, and history of Helicobacter pylori infection, the multivariable adjusted hazard ratios (95% CIs) for incident IM comparing BMIs of <18.5, 23-24.9, 25.0-29.9 and >30 with a BMI of 18.5-22.9 kg/m2 were 0.84 (0.64-1.09), 1.03 (0.93-1.16), 1.07 (0.96-1.20) and 1.48 (1.20-1.83), respectively. These associations did not differ by clinically relevant subgroups. Risk of endoscopic AG also increased as baseline BMI category increased.
CONCLUSIONS:
In a large cohort of Korean men and women, obesity was independently associated with increased incidence of endoscopic AG and IM.
IMPACT:
Excessive adiposity appears to play a role in development of stomach precursor lesions of stomach cancer, requiring further studies to determine that whether strategies to reduce obesity will also help reduce precancerous lesions and, in turn, gastric cancer.

Inflammation markers and risk of developing hypertension: a meta-analysis of cohort studies.
Jayedi A, Rahimi K, Bautista LE, Nazarzadeh M, Zargar MS, Shab-Bidar S.
Heart. 2019 Jan 30. pii: heartjnl-2018-314216. doi: 10.1136/heartjnl-2018-314216. [Epub ahead of print]
PMID: 30700522
Abstract
OBJECTIVE:
To systematically assess the association of circulating inflammation markers with the future risk of hypertension.
METHODS:
We did a systematic literature search of PubMed and Scopus, from database inception to July 10, 2018. Prospective and retrospective cohort studies evaluating the association of circulating C reactive protein (CRP), high-sensitive CRP (hs-CRP), interleukin 6 (IL-6) and IL-1β to the risk of developing hypertension in the general population were included. The relative risks (RRs) for the top versus bottom tertiles of circulating biomarkers were calculated using a fixed-effects/random-effects model. A potential non-linear dose-response association was tested.
RESULTS:
Fourteen prospective cohort studies, two retrospective cohort studies and five nested case-control studies involving 142 640 participants and 20 676 cases were identified. The RR for the third versus first tertiles of circulating CRP was 1.23 (95% CI 1.11 to 1.35; I2=59%, n=12). The association remained unchanged after adjustment for body mass index. The RRs for other biomarkers were as follows: hs-CRP (RR 1.20, 95% CI 1.02 to 1.37; I2=74%, n=7), IL-6 (RR 1.51, 95% CI 1.30 to 1.71; I2=0%, n=5), and IL-1β (RR 1.22, 95% CI 0.92 to 1.51; I2=0%, n=3). A non-linear dose-response meta-analysis demonstrated that the risk of hypertension increased linearly with increasing circulating inflammation markers, even within the low-risk and intermediate-risk categories.
CONCLUSIONS:
Higher levels of circulating CRP, hs-CRP and IL-6, but not IL-1β, were associated with the risk of developing hypertension. The association persisted in subgroups of studies defined by major sources of heterogeneity.
KEYWORDS:
hypertension; inflammatory markers; meta-analysis

The Effects of Three Different Doses of Caffeine on Jumping and Throwing Performance: A Randomized, Double-Blind, Crossover Study.
Sabol F, Grgic J, Mikulic P.
Int J Sports Physiol Perform. 2019 Jan 31:1-25. doi: 10.1123/ijspp.2018-0884. [Epub ahead of print]
PMID: 30702372
Abstract
PURPOSE::
To examine the acute effects of three doses of caffeine on upper- and lower-body ballistic exercise performance, and to explore if habitual caffeine intake impacts the acute effects of caffeine ingestion on ballistic exercise performance.
METHODS::
Twenty recreationally active male participants completed medicine ball throw and vertical jump tests under four experimental conditions (placebo, 2, 4, and 6 mg·kg-1 of caffeine).
RESULTS::
One-way repeated measures ANOVA with subsequent post hoc analyses indicated that performance in the medicine ball throw test improved, compared to placebo, only with a 6 mg·kg-1 dose of caffeine (P=0.032). Effect size, calculated as the mean difference between the two measurements divided by the pooled standard deviation, amounted to 0.29 (+3.7%). For the vertical jump test, all three caffeine doses were effective (compared to placebo) for acute increases in performance (P values ranged from 0.022 to 0.044; effect sizes from 0.35 to 0.42; percent changes from +3.7% to +4.1%). A two-way repeated measures ANOVA indicated that there was no significant group x condition interaction effect, suggesting comparable responses between low (≤100 mg·day-1) and moderate-to-high (>100 mg·day-1) caffeine users to the experimental conditions.
CONCLUSIONS::
Caffeine doses of 2, 4, and 6 mg·kg-1 seem to be effective for acute enhancements in lower-body ballistic exercise performance in recreationally trained male individuals. For the upper-body ballistic exercise performance, only a caffeine dose of 6 mg·kg-1 seems to be effective. The acute effects of caffeine ingestion do not seem to be impacted by habitual caffeine intake; however, this requires further exploration.

Inadequate fat or carbohydrate intake was associated with an increased incidence of type 2 diabetes mellitus in Korean adults: a 12-year community-based prospective cohort study.
Ha K, Joung H, Song Y.
Diabetes Res Clin Pract. 2019 Jan 28. pii: S0168-8227(18)31244-0. doi: 10.1016/j.diabres.2019.01.024. [Epub ahead of print]
PMID: 30703429
Abstract
AIMS:
Few studies have focused on the relationship between long-term fat intake and type 2 diabetes mellitus (T2D) risk in Asia where fat intake is relatively lower than the Western countries. We examined association of dietary fat and carbohydrate intake with incidence of T2D among Korean adults.
METHODS:
Based on the data from the Korean Genome and Epidemiology Study, a total of 5,595 adults aged 40-69 years without diabetes, cardiovascular diseases or any cancer at baseline were included. Dietary intake was measured by the validated semi-quantitative food frequency questionnaire. Cox proportional hazards regression analysis was used to calculate multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs).
RESULTS:
During a median follow-up of 138-months, 1,010 cases of T2D were newly determined. The proportion of participants with fat intake less than 15% of total energy and with carbohydrate intake more than 65% of total energy was 59.0% and 88.9%, respectively. After adjusting for confounders, a very-low-fat intake was associated with an increased risk of T2D (RR of Quartile 1 vs Quartile 4, 1.74; 95% CI, 1.18-2.57; p for trend=0.0058) in women. A very-high-carbohydrate intake was associated with an increased risk of T2D in men (RR of Quartile 4 vs Quartile 1, 1.54; 95% CI, 1.03-2.30; p for trend=0.0124) and women (RR of Quartile 4 vs Quartile 1, 1.69; 95% CI, 1.08-2.67; p for trend=0.0376).
CONCLUSIONS:
A very-low-fat or very-high-carbohydrate intake may increase the T2D risk and might be associated with lower intake of various nutrients and unbalanced macronutrient composition.
KEYWORDS:
Korea; high-carbohydrate diet; low-fat diet; type 2 diabetes mellitus

Effects of seafood consumption and toenail mercury and selenium levels on cognitive function among American adults: 25 y of follow up.
Mao X, Chen C, Xun P, Daviglus M, Steffen LM, Jacobs DR Jr, Van Horn L, Sidney S, Zhu N, He K.
Nutrition. 2018 Nov 24;61:77-83. doi: 10.1016/j.nut.2018.11.002. [Epub ahead of print]
PMID: 30703573
Abstract
OBJECTIVES:
The aim of this study was to examine the longitudinal association between seafood and intake of long-chain ω-3 polyunsaturated fatty acids (LCω-3 PUFA) and cognitive function and to explore the possible effect modifications owing to mercury (Hg) and selenium (Se) levels.
METHODS:
Participants (N = 3231) from the CARDIA (Coronary Artery Risk Development in Young Adults) study underwent baseline examination and were reexamined in eight follow-up visits. Diet was assessed at baseline and in exam years 7 and 20. Toenail Hg and Se were measured at exam year 2. Cognitive function was measured at exam year 25 using three tests: Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and the Stroop test. The general linear regression model was used to examine cumulative average intakes of LCω-3 PUFA and seafood in relation to the cognitive test scores; and to explore the possible effect modifications caused by Hg and Se.
RESULTS:
LCω-3 PUFA intake was significantly associated with better performance in the DSST test (quintile 5 versus quintile 1; mean difference = 1.74; 95% confidence interval, 0.19-3.29; Ptrend, 0.048]), but not in the RAVLT and Stroop tests. Similar results were observed for intakes of eicosapentaenoic acid, docosahexaenoic acid, and non-fried seafood. The observed associations were more pronounced in participants with body mass index ≥25 kg/m2, but not significantly modified by toenail Hg or Se.
CONCLUSION:
This longitudinal study supported the hypothesis that LCω-3 PUFA or non-fried seafood intake is associated with better cognitive performance in psychomotor speed among US adults, especially those who are overweight or obese.
KEYWORDS:
Cognitive function; Hg; LCω-3 PUFA; Se; Seafood consumption

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Omega-3 fatty acids, cardiovascular risk, and the resolution of inflammation.
Bäck M, Hansson GK.
FASEB J. 2019 Feb;33(2):1536-1539. doi: 10.1096/fj.201802445R.
PMID: 30703872
Abstract
Although a high marine food intake is considered cardioprotective, randomized trials of ω-3 fatty acids initially generated conflicting results in terms of the role of ω-3 supplementation in cardiovascular prevention. This work demonstrates the results of the 3 most recent clinical trials with ω-3 fatty acids are put into the context of possible mechanisms mediating their beneficial cardiovascular effects. In particular, the randomized Reduction of Cardiovascular Events with EPA Intervention Trial (REDUCE-IT) showed that icosapent ethyl, which is the ethyl ester form of the ω-3 fatty acid eicosapentaenoic acid (EPA), induced a significant reduction of cardiovascular events. Importantly, EPA serves as a substrate for the formation of the specialized proresolving mediator resolvin E1 (RvE1), which stimulates the resolution of inflammation. RvE1 reduces atherosclerosis and intimal hyperplasia by means of its specific receptor ERV1/ChemR23. The decreased levels of proinflammatory and proatherosclerotic leukotrienes by ω-3 fatty acids may further contribute to a beneficial inflammatory balance. Consequently, the Rv/leukotriene ratio is emerging as a marker of nonresolving vascular inflammation. Recent experimental studies have shown that anti-inflammatory and proresolving effects of lipid mediators derived from ω-3 fatty acids inhibit atherosclerosis independently of cholesterol and triglyceride levels. The results of the 3 most recent clinical trials of ω-3 fatty acid supplementation indicate an importance of the type and dose of ω-3 supplementation and highlight the need for risk stratification in the patient selection for ω-3 supplementation for either primary or secondary prevention of cardiovascular disease.-Bäck, M., Hansson, G. K. Omega-3 fatty acids, cardiovascular risk, and the resolution of inflammation.
KEYWORDS:
atherosclerosis; leukotrienes; resolvins

Breakfast consumption and the risk of depressive symptoms: The Furukawa Nutrition and Health Study.
Miki T, Eguchi M, Kuwahara K, Kochi T, Akter S, Kashino I, Hu H, Kurotani K, Kabe I, Kawakami N, Nanri A, Mizoue T.
Psychiatry Res. 2019 Jan 24;273:551-558. doi: 10.1016/j.psychres.2019.01.069. [Epub ahead of print]
PMID: 30710811
Abstract
Breakfast consumption has been suggested to influence mood, but prospective evidence on this issue is limited. We prospectively investigated the association between the frequency of breakfast consumption and the risk of depressive symptoms in Japanese employees. Participants were 716 employees aged 19-68 years who were free from depressive symptoms and mental disorders at baseline and who attended the 3-year follow-up survey. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. The frequency of breakfast consumption was categorized into "daily", "5-6 times/week", "3-4 times/week", "1-2 times/week", or "≤1 times/week". Logistic regression was used to estimate odds ratios of depressive symptoms according to breakfast consumption adjusted for dietary and lifestyle factors. Participants who consumed breakfast ≤1 times/week had an increased risk of depressive symptoms compared to those who ate breakfast every day, even after adjusting for other dietary factors (multivariable-adjusted odds ratio 2.92; 95% confidence interval, 1.37-6.22) The risk of depressive symptoms tended to increase with decreasing frequency of breakfast consumption (P for trend = 0.02). The omission of breakfast is related to increased risk of depressive symptoms among Japanese employees, independently of other dietary and non-dietary factors.
KEYWORDS:
Breakfast; Depression risk; Japanese; Prospective studies

Effect of salt intake reduction on nocturia in patients with excessive salt intake.
Matsuo T, Miyata Y, Sakai H.
Neurourol Urodyn. 2019 Feb 1. doi: 10.1002/nau.23929. [Epub ahead of print]
PMID: 30706965
Abstract
AIMS:
To assess the efficacy of salt reduction for improving nocturia in patients with high salt intake.
METHODS:
Changes in lower urinary symptoms and frequency volume chart by salt intake (men: 8 g/day; women: ≥7 g/day) were analyzed in this prospective study. Patients were instructed to use a brochure for salt intake restriction via interview once every four weeks. The daily salt intake was estimated by using spot urine samples.
RESULTS:
Two-hundred twenty-three (69.5%) patients were successful in reducing their daily salt intake (S group), whereas 98 (30.5%) patients failed to reduce their salt intake (F group). In the S group, nocturia improved from 2.3 ± 0.9 to 1.4 ± 1.0, and nocturnal polyuria index (NPi) improved from 30.2 ± 7.5 to 27.7 ± 7.3% (P < 0.001). In the Core Lower Urinary Tract Symptom Score (CLSS) of the S group, Q3 (urgency) improved from 1.0 ± 1.0 to 0.9 ± 1.0 (P = 0.001); Q1 (diurnal frequency) (P < 0.001), and Q2 (nocturia) also improved (P < 0.001). Moreover, the quality of life parameter improved significantly (P < 0.001). The patients in the F group did not have improvements in any symptom during the study period.
CONCLUSIONS:
Patients with nocturia who also have high salt intake should be advised to reduce their salt intake, as a lifestyle modification. Our results support the importance of randomized clinical trials with larger populations and the appropriate inclusion/exclusion criteria to conclude the clinical usefulness of salt reduction in this patient cohort.
KEYWORDS:
lower urinary tract symptoms; nocturia; salt intake reduction; treatment

Fasting ramp up human metabolism, study
Quantification of blood metabolites from 4 volunteers during fasting.
By Pranjal Mehar - January 31, 2019
https://www.techexplorist.com/fasting-ramp-up-human-metabolism-study/20547/
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Diverse metabolic reactions activated during 58-hr fasting are revealed by non-targeted metabolomic analysis of human blood.
Teruya T, Chaleckis R, Takada J, Yanagida M, Kondoh H.
Sci Rep. 2019 Jan 29;9(1):854. doi: 10.1038/s41598-018-36674-9.
PMID: 30696848 Free PMC Article
https://www.nature.com/articles/s41598-018-36674-9.pdf
Abstract
During human fasting, metabolic markers, including butyrates, carnitines, and branched-chain amino acids, are upregulated for energy substitution through gluconeogenesis and use of stored lipids. We performed non-targeted, accurate semiquantitative metabolomic analysis of human whole blood, plasma, and red blood cells during 34-58 hr fasting of four volunteers. During this period, 44 of ~130 metabolites increased 1.5~60-fold. Consistently fourteen were previously reported. However, we identified another 30 elevated metabolites, implicating hitherto unrecognized metabolic mechanisms induced by fasting. Metabolites in pentose phosphate pathway are abundant, probably due to demand for antioxidants, NADPH, gluconeogenesis and anabolic metabolism. Global increases of TCA cycle-related compounds reflect enhanced mitochondrial activity in tissues during fasting. Enhanced purine/pyrimidine metabolites support RNA/protein synthesis and transcriptional reprogramming, which is promoted also by some fasting-related metabolites, possibly via epigenetic modulations. Thus diverse, pronounced metabolite increases result from greatly activated catabolism and anabolism stimulated by fasting. Anti-oxidation may be a principal response to fasting.

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Before evening falls: Perspectives of a good old age and healthy ageing among oldest-old Swedish men.
Carstensen G, Rosberg B, Mc Kee KJ, Åberg AC.
Arch Gerontol Geriatr. 2019 Jan 19;82:35-44. doi: 10.1016/j.archger.2019.01.002. [Epub ahead of print]
PMID: 30711841
Abstract
The late life experiences of men in the oldest-old age group have been under-researched, and their perspectives on ageing successfully neglected. This study explored the perspectives of oldest-old Swedish men on what a 'good old age' and ageing successfully meant to them. A purposive sample of 17 men, aged 85-90 years, was drawn from the Uppsala Longitudinal Study of Adult Men. An interview guide explored participants' perspectives on their ageing experiences and how they viewed ageing successfully. Participants were interviewed twice, with 1-2 weeks between interviews, and both interviews were recorded and transcribed. Content analysis identified four themes: i) Adaptation, concerning the ability to adapt to growing old with increasing limitations; ii) Sustaining Independence, related to financial resources and good health as the foundation for independence; iii) Belongingness, representing close relationships, established friendships, and the significance of the spouse; and iv) Perspectives of Time, also a common thread in all themes, in which past life experiences create an existential link between the past, the present and the future, establishing continuity of the self and enhancing life satisfaction. The participants presented themselves as active agents involved in maintaining meaning and achieving life satisfaction; a process related to the ability to manage changes in life. Our findings have resonance with models of healthy or successful ageing, but also diverge in important ways, since such models do not consider the significance of an individual's life history for their present well-being, and primarily conceptualise health as an outcome, rather than as a resource.
KEYWORDS:
Adaptation; Belongingness; Continuity; Independence; Life satisfaction; Men; Older audults; Time; healthy aging

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A Nested Case-Control Study on Plasma Vitamin E and Risk of Cancer: Evidence of Effect Modification by Selenium.
Wang J, Guo H, Lin T, Song Y, Zhang H, Wang B, Zhang Y, Li J, Huo Y, Wang X, Qin X, Xu X.
J Acad Nutr Diet. 2019 Jan 31. pii: S2212-2672(18)30852-9. doi: 10.1016/j.jand.2018.11.017. [Epub ahead of print]
PMID: 30713028

Abstract
BACKGROUND:
Evidence from epidemiologic studies has been inconsistent regarding the role of vitamin E in cancer incidence risk.
OBJECTIVE:
The aim of this study was to evaluate the prospective association between baseline plasma vitamin E levels and subsequent cancer risk in Chinese adults with hypertension, and to identify effect modifiers.
DESIGN:
A nested, case-control study was conducted from 20,702 hypertensive participants in the China Stroke Primary Prevention Trial, a randomized, double-blind, controlled trial, conducted from May 2008 to August 2013.
PARTICIPANTS:
The current study included 229 new cancer cases and 229 controls matched for age (±1 year), sex, treatment group, and study site.
MAIN OUTCOME MEASURES:
Plasma vitamin E was measured by liquid chromatography with tandem quadrupole mass spectrometers and plasma selenium was measured by inductively coupled plasma mass spectrometry using Thermo Fisher iCAP Q ICP-MS.
STATISTICAL ANALYSES:
Odds ratios (OR) of cancer in relation to plasma concentrations of vitamin E were calculated using conditional logistic regression models.
RESULTS:
Median follow-up duration was 4.5 years. Overall, vitamin E was not associated with subsequent risk of total cancer (per 1-mg/L [2.3 μmol/L] increase: OR 1.01, 95% CI 0.93 to 1.09) and non-gastrointestinal cancer (OR 1.10, 95% CI 0.98 to 1.24). However, there was a significant, inverse association between vitamin E and gastrointestinal cancer (OR 0.86, 95% CI 0.75 to 0.99), particularly esophageal cancer (OR 0.67, 95% CI 0.48 to 0.95). Moreover, high vitamin E decreased the risk of total cancer (OR 0.91, 95% CI 0.84 to 0.99) and gastrointestinal cancer (OR 0.83, 95% CI 0.73 to 0.95) among patients with high selenium levels (median≥83.7 μg/L [1.1 μmol/L]), and increased the risk of total cancer (OR 1.13, 95% CI 1.00 to 1.26) and non-gastrointestinal cancer (OR 1.25, 95% CI 1.03 to 1.50) among those with low selenium levels (<83.7 μg/L [1.1 μmol/L]).
CONCLUSIONS:
This study suggests that higher levels of plasma vitamin E are associated with reduced risk of gastrointestinal cancer. High vitamin E decreased the risk of total cancer among patients with high selenium levels, but increased the risk of total cancer among those with low selenium levels.
KEYWORDS:
Antioxidant; Cancer incidence; Hypertension; Selenium; Vitamin E


Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta-analysis, and network meta-analysis of randomized trials with 94,283 participants.
Yebyo HG, Aschmann HE, Kaufmann M, Puhan MA.
Am Heart J. 2019 Jan 10;210:18-28. doi: 10.1016/j.ahj.2018.12.007. [Epub ahead of print] Review.
PMID: 30716508
Abstract
The current guidelines of statins for primary cardiovascular disease (CVD) prevention were based on results from systematic reviews and meta-analyses that suffer from limitations.
METHODS:
We searched in PubMed for existing systematic reviews and individual open-label or double-blinded randomized controlled trials that compared a statin with a placebo or another, which were published in English until January 01, 2018. We performed a random-effect pairwise meta-analysis of all statins as a class and network meta-analysis for the specific statins on different benefit and harm outcomes.
RESULTS:
In the pairwise meta-analyses, statins as a class showed statistically significant risk reductions on non-fatal MI (risk ratio [RR] 0.62, 95% CI 0.53-0.72), CVD mortality (RR 0.80, 0.71-0.91), all-cause mortality (RR 0.89, 0.85-0.93), non-fatal stroke (RR 0.83, 0.75-0.92), unstable angina (RR 0.75, 0.63-0.91), and composite major cardiovascular events (RR 0.74, 0.67-0.81). Statins increased statistically significantly relative and absolute risks of myopathy (RR 1.08, 1.01-1.15; Risk difference [RD] 13, 2-24 per 10,000 person-years); renal dysfunction (RR 1.12, 1.00-1.26; RD 16, 0-36 per 10,000 person-years); and hepatic dysfunction (RR 1.16, 1.02-1.31; RD 8, 1-16 per 10,000 person-years). The drug-level network meta-analyses showed that atorvastatin and rosuvastatin were most effective in reducing CVD events while atorvastatin appeared to have the best safety profile.
CONCLUSIONS:
All statins showed statistically significant risk reduction of CVD and all-cause mortality in primary prevention populations while increasing the risk for some harm risks. However, the benefit-harm profile differed by statin type. A quantitative assessment of the benefit-harm balance is thus needed since meta-analyses alone are insufficient to inform whether statins provide net benefit.

Cognitive ageing trajectories and mortality of Chinese oldest-old.
Hu X, Gu S, Sun X, Gu Y, Zhen X, Li Y, Huang M, Wei J, Dong H.
Arch Gerontol Geriatr. 2019 Jan 29;82:81-87. doi: 10.1016/j.archger.2019.01.018. [Epub ahead of print]
PMID: 30716682
https://sci-hub.tw/https://linkinghub.elsevier.com/retrieve/pii/S0167494319300202
Abstract
OBJECTIVE:
This study aims to identify distinctive cognitive trajectories jointly with mortality probabilities and to explore factors related to the particular trajectories of cognitive ageing in China.
METHOD:
6842 individuals aged 80 years and above from 7 waves of the Chinese Longitudinal Healthy Longevity Survey were assessed with the Mini-Mental State Examination for up to 16 years. A group-based trajectory model was used to jointly estimate cognitive ageing and mortality trajectories; and to explore the factors related to membership of the trajectory groups.
RESULTS:
A four-group model best fit the data. For all groups, the cognitive function declined with age according to different rates. Group 4, 3, 2, and 1 showed slow (prevalence 52.8%), moderate (31.1%), progressive (12.6%) and rapid (3.5%) cognitive decline, respectively. Mortality probability trajectories followed a hierarchy in consistence with cognitive trajectories approximately. Females, illiteracy, and those born in rural areas were less likely to belong to the most favorable trajectory group.
CONCLUSIONS:
The heterogeneity of cognitive ageing was identified among Chinese oldest-old. Childhood socioeconomic status, especially education, was associated with the rate of cognitive decline.
KEYWORDS:
China; Cognition; Group-based trajectory model; Heterogeneity; Mini Mental State examination

Pure fruit juice and fruit consumption and the risk of CVD: the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) study.
Scheffers FR, Boer JMA, Verschuren WMM, Verheus M, van der Schouw YT, Sluijs I, Smit HA, Wijga AH.
Br J Nutr. 2019 Feb;121(3):351-359. doi: 10.1017/S0007114518003380. Epub 2018 Nov 15.
PMID: 30428938
https://sci-hub.tw/10.1017/S0007114518003380
Abstract
Dietary guidelines for pure fruit juice consumption differ between countries, regarding the question whether pure fruit juice is an acceptable alternative for fruit. Currently, little is known about pure fruit juice consumption and the risk of CVD. In this prospective cohort study, we studied the association of pure fruit juice and fruit consumption with the incidence of fatal and non-fatal CVD, CHD and stroke and investigated the differences in association with pure fruit juice consumption between low and high fruit consumers. A validated FFQ was used to estimate dietary intake of 34 560 participants (26·0 % men and 74·0 % women) aged 20-69 years from the European Prospective Investigation into Cancer and Nutrition-Netherlands study. Adjusted hazard ratios (HR) were estimated using Cox regression after average follow-up of 14·6 years. Compared with no consumption, pure fruit juice consumption up to 7 glasses/week - but not consumption of ≥8 glasses - was significantly associated with reduced risk of CVD and CHD, with HR from 0·83 (95 % CI 0·73, 0·95) to 0·88 (95 % CI 0·80, 0·97). Consumption of 1-4 and 4-8 glasses/week was significantly associated with lower risk of stroke with HR of 0·80 (95 % CI 0·64, 0·99) and 0·76 (95 % CI 0·61, 0·94), respectively. Associations did not differ considerably between low and high fruit consumers. The highest three quintiles of fruit consumption (≥121 g/d) were significantly associated with lower incidence of CVD, with HR of 0·87 (95 % CI 0·78, 0·97) and 0·88 (95 % CI 0·80, 0·98). In conclusion, although we observed favourable associations of moderate pure fruit juice consumption with CVD, for now consumption of whole fruit should be preferred because the evidence of the health benefits of fruit is more conclusive.
KEYWORDS:
DHD15-index Dutch Healthy Diet index 2015; EPIC-NL European Prospective Investigation into Cancer and Nutrition–Netherlands; HR hazard ratio; ICD International Classification of Diseases; MORGEN Monitoring Project on Chronic Disease Risk Factors; TC total cholesterol; CHD; CVD; Dietary guidelines; European Prospective Investigation into Cancer and Nutrition–Netherlands; Fruit; Pure fruit juice; Stroke

Edited by AlPater

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How Effective Are Dietitians in Weight Management? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Williams LT, Barnes K, Ball L, Ross LJ, Sladdin I, Mitchell LJ.
Healthcare (Basel). 2019 Feb 1;7(1). pii: E20. doi: 10.3390/healthcare7010020. Review.
PMID: 30717197
Abstract
Effective, evidence-based strategies to prevent and treat obesity are urgently required. Dietitians have provided individualized weight management counselling for decades, yet evidence of the effectiveness of this intervention has never been synthesized. The aim of this study was to examine the effectiveness of individualized nutrition care for weight management provided by dietitians to adults in comparison to minimal or no intervention. Databases (Cochrane, CINAHL plus, MedLine ovid, ProQuest family health, PubMed, Scopus) were searched for terms analogous with patient, dietetics and consultation with no date restrictions. The search yielded 5796 unique articles, with 14 randomized controlled trials meeting inclusion criteria. The risk of bias for the included studies ranged from unclear to high. Six studies found a significant intervention effect for the dietitian consultation, and a further four found significant positive change for both the intervention and control groups. Data were synthesized through random effects meta-analysis from five studies (n = 1598) with weight loss as the outcome, and from four studies (n = 1224) with Body Mass Index (BMI) decrease as the outcome. Groups receiving the dietitian intervention lost an additional 1.03 kg (95% CI:-1.40; -0.66, p < 0.0001) of weight and 0.43 kg/m2 (95% CI:-0.59, -0.26; p < 0.0001) of BMI than those receiving usual care. Heterogeneity was low for both weight loss and BMI, with the pooled means varying from 1.26 to -0.93 kg and -0.4 kg/m² for weight and BMI, respectively, with the removal of single studies. This study is the first to synthesize evidence on the effectiveness of individualized nutrition care delivered by a dietitian. Well-controlled studies that include cost-effectiveness measures are needed to strengthen the evidence base.
KEYWORDS:
dietetic consultation; dietitian; nutrition care; nutritional management; primary health care; workforce

Body Mass Index, Intensive Blood Pressure Management, and Cardiovascular Events in the Systolic Blood Pressure Intervention Trial (SPRINT).
Oxlund CS, Pareek M, Rasmussen BSB, Vaduganathan M, Biering-Sørensen T, Byrne C, Almarzooq Z, Olsen MH, Bhatt DL.
Am J Med. 2019 Feb 2. pii: S0002-9343(19)30133-0. doi: 10.1016/j.amjmed.2019.01.024. [Epub ahead of print]
PMID: 30721655
https://sci-hub.tw/10.1016/j.amjmed.2019.01.024
Abstract
BACKGROUND:
It is unclear whether intensive blood pressure management is well-tolerated and affects risk uniformly across the body mass index (BMI) spectrum.
METHODS:
The randomized, controlled Systolic Blood Pressure Intervention Trial (SPRINT) included 9,361 individuals ≥50 years at high cardiovascular risk, without diabetes mellitus, and a systolic blood pressure 130-180 mmHg. Participants were randomized to intensive versus standard antihypertensive treatment and evaluated for the primary composite efficacy endpoint of acute coronary syndromes, stroke, heart failure, or cardiovascular death. The primary safety endpoint was serious adverse events. We used restricted cubic splines to determine the relationship between BMI, response to intensive blood pressure lowering, and clinical outcomes in SPRINT.
RESULTS:
BMI measurements could be calculated for 9,284 (99.2%) individuals. Mean BMI was similar between the two treatment groups (intensive group 29.9±5.8 kg/m2 vs. standard group 29.8± 5.7 kg/m2; P=0.39). Median follow-up was 3.3 years (range 0-4.8 years). BMI had a significant, J-shaped association with risk of all-cause mortality, stroke, and serious adverse events (P<0.05 for all), but these were no longer significant after accounting for key clinical factors (P>0.05 for all). Intensive blood pressure lowering reduced the primary efficacy endpoint and increased the primary safety endpoint compared with standard targets, consistently across the BMI spectrum (Pinteraction>0.05).
CONCLUSION:
The overall efficacy and safety of intensive blood pressure lowering did not appear to be modified by baseline BMI among high-risk older adults.
KEYWORDS:
blood pressure; body mass index; hypertension; safety

Association of flavonoids and flavonoid-rich foods with all-cause mortality: The Blue Mountains Eye Study.
Bondonno NP, Lewis JR, Blekkenhorst LC, Bondonno CP, Shin JH, Croft KD, Woodman RJ, Wong G, Lim WH, Gopinath B, Flood VM, Russell J, Mitchell P, Hodgson JM.
Clin Nutr. 2019 Jan 17. pii: S0261-5614(19)30006-8. doi: 10.1016/j.clnu.2019.01.004. [Epub ahead of print]
PMID: 30718096
Abstract
BACKGROUND:
Higher intakes of flavonoids provide health benefits, however, the importance of each flavonoid class and which population groups may receive the greatest protection from higher flavonoid intake warrants further investigation.
OBJECTIVE:
To explore the associations of flavonoid and flavonoid-rich wholefood intakes with all-cause mortality and the moderating effects of early mortality risk factors.
DESIGN:
The study included 2349 participants of The Blue Mountains Eye Study, with a mean ± SD age at baseline of 64.7 ± 9.2 years. Flavonoid intake was calculated from baseline food frequency questionnaires using US Department of Agriculture food composition databases. Associations were examined using adjusted Cox proportional hazards models.
RESULTS:
After 14 years of follow-up, 677 participants died. There was a flavonoid threshold effect with the greatest risk reduction seen between low and moderate intakes of total flavonoids, flavonoid classes and flavonoid-rich foods. Amongst the whole cohort, participants in the highest tertile of anthocyanidin intake had a significantly lower risk of all-cause mortality [multivariable adjusted HR (95%CI): 0.76 (0.61, 0.94)] when compared to those in the lowest tertile. Amongst participants with at least one early mortality risk factor (smoking, high alcohol consumption, no regular exercise or obesity), risk of all-cause mortality was lower in those in the highest intake tertile for total flavonoids [adjusted HR: 0.77 (0.59, 1.00)], flavan-3-ols [0.75 (0.58, 0.98)], anthocyanidins [0.70 (0.54, 0.92)], and proanthocyanidins [0.69 (0.52, 0.92)], compared to those in the lowest tertile. No similar associations were observed among those without any risk factors. Similarly, consumption of apples, tea and the individual flavonoid compounds, quercetin and epicatechin, were associated with a lower risk of all-cause mortality among participants with at least one risk factor, but not amongst other participants.
CONCLUSION:
Moderate to high intakes of flavonoids and certain flavonoid subclasses may provide health benefits, particularly for individuals with at least one early mortality risk factor.
KEYWORDS:
All-cause mortality; Flavonoid-rich foods; Flavonoids; Prospective cohort study

Dietary Niacin Intake Predicts the Decrease of Liver Fat Content During a Lifestyle Intervention.
Linder K, Willmann C, Kantartzis K, Machann J, Schick F, Graf M, Kümmerle S, Häring HU, Fritsche A, Stefan N, Wagner R.
Sci Rep. 2019 Feb 4;9(1):1303. doi: 10.1038/s41598-018-38002-7.
PMID: 30718741
https://www.nature.com/articles/s41598-018-38002-7.pdf
Abstract
Niacin inhibits fatty acid flux from adipose tissue to liver, reduces hepatic triglyceride synthesis and increases hepatic lipid oxidation. Thus, niacin may have a role in the regulation of liver fat content in humans. We tested if dietary intake of niacin predicts change of liver fat content during a lifestyle intervention. To this end, we estimated the composition of diet from diaries of 202 healthy subjects at risk of type 2 diabetes undergoing lifestyle intervention comprising physical activity and diet counselling. Total-, subcutaneous- and visceral adipose tissue mass were measured by magnetic resonance (MR) tomography and liver fat content by 1H-MR spectroscopy at baseline and after 9 months of follow-up. Among fat compartments, liver fat content showed the largest decrease (-32%, p < 0.0001). High baseline niacin intake predicted a larger decrease of liver fat (p = 0.004). Subjects in the highest quartile of niacin intake at baseline also had the largest decrease of liver fat (1st:-10%; 2nd:-27%; 3rd:-35%; 4th:-37%). Among 58 subjects with nonalcoholic fatty liver disease (NAFLD) at baseline, NAFLD resolved in 23 subjects during the lifestyle intervention. For one standard deviation increase in niacin intake, the odds ratio for resolution of NAFLD was 1.77 (95% CI, 1.00-3.43). High dietary niacin intake may have a favorable effect on the reduction of liver fat during lifestyle intervention.

Soy intake and vasomotor menopausal symptoms among midlife women: a pooled analysis of five studies from the InterLACE consortium.
Dunneram Y, Chung HF, Cade JE, Greenwood DC, Dobson AJ, Mitchell ES, Woods NF, Brunner EJ, Yoshizawa T, Anderson D, Mishra GD.
Eur J Clin Nutr. 2019 Feb 4. doi: 10.1038/s41430-019-0398-9. [Epub ahead of print]
PMID: 30718804
Abstract
BACKGROUND/OBJECTIVES:
Phytoestrogen rich-foods such as soy may be associated with less frequent/severe vasomotor menopausal symptoms (VMS), although evidence is limited. We thus investigated the associations between the consumption of soy products and soy milk and the frequency/severity of VMS.
SUBJECTS/METHODS:
We pooled data from 19,351 middle-aged women from five observational studies in Australia, UK, USA, and Japan that contribute to the International Collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on soy consumption, VMS and covariates were collected by self-report. We included 11,006 women who had complete data on soy consumption, VMS and covariates at baseline for the cross-sectional analysis. For the prospective analysis, 4522 women who were free of VMS at baseline and had complete data on VMS at follow-up were considered. Multinomial logistic regression and binary logistic regression models were used.
RESULTS:
No statistically significant evidence of an association was found between soy products (relative risk ratio (RRR): 0.92, 95% CI: 0.76-1.11) or soy milk (RRR: 1.24, 95% CI: 0.93-1.65) and the likelihood of reporting frequent or severe VMS cross-sectionally. Prospective results indicated that frequent consumption of soy products (odds ratio (OR): 0.63, 95% CI: 0.45-0.89) but not soy milk (OR: 1.11, 95% CI: 0.85-1.45) was associated with lower likelihood of reporting subsequent VMS, after adjustment for socio-demographic and reproductive factors.
CONCLUSIONS:
These are the first ever findings from pooled observational data of association between consumption of soy products and VMS.

Plant-Based Diet, Cholesterol, and Risk of Gallstone Disease: A Prospective Study.
Chang CM, Chiu THT, Chang CC, Lin MN, Lin CL.
Nutrients. 2019 Feb 4;11(2). pii: E335. doi: 10.3390/nu11020335.
PMID: 30720747
https://www.mdpi.com/2072-6643/11/2/335/htm
Abstract
Vegetarian diets may lower symptomatic gallstone disease via cholesterol lowering. This study aimed to examine the risk of symptomatic gallstone disease (GSD) in Taiwanese vegetarians vs. nonvegetarians in a prospective cohort and to explore if this association is related to cholesterol concentration. We prospectively followed 4839 participants, and in the 29,295 person-years of follow-up, 104 new incident GSD cases were confirmed. Diet was assessed through a validated food frequency questionnaire. Symptomatic GSD was ascertained through linkage to the Taiwan National Health Insurance Research Database. Blood cholesterol profiles were measured at recruitment. Cox regression was applied to assess the effect of diet on symptomatic GSD, adjusting for age, education, smoking, alcohol, physical activities, diabetes, kidney diseases, body mass index, lipid-lowering medication, and hypercholesterolemia. Vegetarian diet was associated with a decreased risk of symptomatic GSD compared with nonvegetarian diet in women (hazard ratio {HR}, 0.52; 95% confidence interval [CI], 0.28⁻0.96) but not in men. In women, nonvegetarians with hypercholesterolemia had 3.8 times the risk of GSD compared with vegetarians with normal cholesterol (HR, 3.81, 95% CI, 1.61⁻9.01). A vegetarian diet may therefore protect against GSD independent of baseline hypercholesterolemia. A nonvegetarian diet and hypercholesterolemia may have an additive effect in increasing GSD risk in women.
KEYWORDS:
cholesterol; gallstone disease; prospective cohort; vegetarian diet

Edited by AlPater

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Dietary restriction of iron availability attenuates UPEC pathogenesis in a mouse model of urinary tract infection.
Bauckman KA, Matsuda R, Higgins CB, DeBosch BJ, Wang C, Mysorekar IU.
Am J Physiol Renal Physiol. 2019 Feb 6. doi: 10.1152/ajprenal.00133.2018. [Epub ahead of print]
PMID: 30724105
Abstract
Iron is a critical nutrient required by hosts and pathogens. Uropathogenic Escherichia coli (UPEC), the principal causative agent of urinary tract infections (UTIs), chelate iron for their survival and persistence. Here, we demonstrate that dietary modulation of iron availability limits UPEC burden in a mouse model of UTI. Mice on a low iron diet exhibit reduced systemic and bladder mucosal iron availability, harbor significantly lower bacterial burden, concomitant with dampened inflammation. Hepcidin is a master regulator of iron that controls iron-dependent UPEC intracellular growth. Hepcidin deficient mice ( Hamp1-/- ) exhibit accumulation of iron deposits, persistent bacterial burden in the bladder, and a heightened inflammatory response to UTI. However, a low iron dietary regimen reverses the iron overload and increased bacterial burden phenotypes in Hamp1-/- mice. Thus, modulation of iron levels via diet can reduce UPEC infection and persistence, which may have significant implications for clinical management of UTI.
KEYWORDS:
Ferritin; IL-6; hepcidin; uropathogenic E. coli; urothelium

Meta-regression analysis of the effects of dietary cholesterol intake on LDL and HDL cholesterol.
Vincent MJ, Allen B, Palacios OM, Haber LT, Maki KC.
Am J Clin Nutr. 2019 Jan 1;109(1):7-16. doi: 10.1093/ajcn/nqy273.
PMID: 30596814
Abstract
BACKGROUND:
Elevated low-density lipoprotein (LDL) cholesterol is a major risk factor for cardiovascular disease. Dietary guidance recommends reducing saturated fatty acid, trans fatty acid, and cholesterol intakes to reduce circulating LDL cholesterol. Cholesterol intake may also affect high-density lipoprotein (HDL)-cholesterol concentrations, but its impact has not been fully quantified.
OBJECTIVES:
The aims of this study were to investigate the dose-response relation between changes in dietary cholesterol intake and changes in lipoprotein-cholesterol markers for cardiovascular disease risk and to provide a reference for clinicians on how changes in dietary cholesterol intake affect circulating cholesterol concentrations, after accounting for intakes of fatty acids.
METHODS:
We used a Bayesian approach to meta-regression analysis, which uses Markov chain Monte Carlo techniques, to assess the relation between the change in dietary cholesterol (adjusted for dietary fatty acids) and changes in LDL and HDL cholesterol based on the use of data from randomized dietary intervention trials.
RESULTS:
Fifty-five studies (2652 subjects) were included in the analysis. The nonlinear Michaelis-Menten (MM) and Hill models best described the data across the full spectrum of dietary cholesterol changes studied (0-1500 mg/d). Mean predicted changes in LDL cholesterol for an increase of 100 mg dietary cholesterol/d were 1.90, 4.46, and 4.58 mg/dL for the linear, nonlinear MM, and Hill models, respectively.
CONCLUSIONS:
The change in dietary cholesterol was positively associated with the change in LDL-cholesterol concentration. The linear and MM models indicate that the change in dietary cholesterol is modestly inversely related to the change in circulating HDL-cholesterol concentrations in men but is positively related in women. The clinical implications of HDL-cholesterol changes associated with dietary cholesterol remain uncertain.

Effect of folate supplementation on insulin sensitivity and type 2 diabetes: a meta-analysis of randomized controlled trials.
Lind MV, Lauritzen L, Kristensen M, Ross AB, Eriksen JN.
Am J Clin Nutr. 2019 Jan 1;109(1):29-42. doi: 10.1093/ajcn/nqy234.
PMID: 30615110
Abstract
BACKGROUND:
Various mechanisms link higher total homocysteine to higher insulin resistance (IR) and risk of type 2 diabetes (T2D). Folate supplementation is recognized as a way to lower homocysteine. However, randomized controlled trials (RCTs) show inconsistent results on IR and T2D outcomes.
OBJECTIVE:
The aim of this study was to examine the effect of folate supplementation on IR and T2D outcomes.
DESIGN:
We conducted a systematic literature search in PubMed, Web of Science, and EMBASE and prior systematic reviews and meta-analyses and identified 29 RCTs (22,250 participants) that assessed the effect of placebo-controlled folate supplementation alone or in combination with other B vitamins on fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), or risk of T2D. The meta-analysis was conducted using both random- and fixed-effects models to calculate weighted mean differences (WMDs) or risk ratios with 95% CIs. Subgroup analyses were conducted based on intervention type (folate alone or in combination with other B vitamins), as well as analysis based on population characteristics, duration, dose, and change in homocysteine.
RESULTS:
When compared with placebo, folate supplementation lowered fasting insulin (WMD: -13.47 pmol/L; 95% CI: -21.41, -5.53 pmol/L; P < 0.001) and HOMA-IR (WMD: -0.57 units; 95% CI: -0.76, -0.37 units; P < 0.0001), but no overall effects were observed for fasting glucose or HbA1c. Heterogeneity was low in all meta-analyses, and subgroup analysis showed no signs of effect modification except for change in homocysteine, with the most pronounced effects in trials with a change of >2.5 µmol/L. Changes in homocysteine after folate supplementation correlated with changes in fasting glucose (β = 0.07; 95% CI: 0.01, 0.14; P = 0.025) and HbA1c (β = 0.46; 95% CI: 0.06, 0.85; P = 0.02). Only 2 studies examined folate supplementation on risk of T2D, and they found no change in RR (pooled RR: 0.91; 95% CI: 0.80, 1.04; P = 0.16).
CONCLUSION:
Folate supplementation might be beneficial for glucose homeostasis and lowering IR, but at present there are insufficient data to conclusively determine the effect on development of T2D.

High iron intake is associated with poor cognition among Chinese old adults and varied by weight status-a 15-y longitudinal study in 4852 adults.
Shi Z, Li M, Wang Y, Liu J, El-Obeid T.
Am J Clin Nutr. 2019 Jan 1;109(1):109-116. doi: 10.1093/ajcn/nqy254.
PMID: 30649164
Abstract
BACKGROUND:
High body iron status has been shown to be associated with adverse health outcomes. However, the relation between high body iron status, body mass index (BMI), and cognition is still understudied.
OBJECTIVE:
This study aimed to examine the association between iron intake and cognitive function in Chinese adults and tested the interaction effect of iron intake and BMI on cognition.
DESIGN:
Longitudinal study data from a nationwide sample (n = 4852; age ≥55 y) from the China Health and Nutrition Survey during 1991-2006 were used. Of the participants, 3302 had completed cognitive screening tests in ≥2 surveys. Cognitive function was assessed in 1997, 2000, 2004, and 2006. Dietary iron intake was obtained from a 3-d food record during home visits in 1991, 1993, 1997, 2000, 2004, and 2006. Multivariable mixed linear regression and logistic regression were used.
RESULTS:
The cumulative mean ± SD iron intake in 1997 of tested subjects was 23.7 ± 11.3 mg/d (25.4 mg/d in men and 22.2 mg/d in women). High iron intake was associated with poor cognition. In fully adjusted models, across the quartiles of iron intake the regression coefficients (95% CIs) were 0, -0.39 (-0.77, -0.01), -0.55 (-0.95, -0.15), and -0.90 (-1.33, -0.47), respectively. Comparing extreme quartiles of iron intake (high), the OR (95% CI) for poor cognitive function was 1.30 (1.04, 1.64). There was a significant interaction between iron intake and BMI. The association between high iron intake and poor cognition was stronger among those with a high BMI than those with a low BMI. Among those with a BMI (kg/m2) >24, across quartiles of iron intake the ORs (95% CIs) for poor cognitive function were 1.00, 1.27 (0.91, 1.78), 1.41 (0.97, 2.04), and 2.04 (1.38, 3.01), respectively.
CONCLUSION:
Higher iron intake is associated with poor cognition in Chinese adults, especially among those with a high BMI.

Efficacy of Methionine-Restricted Diets on Cancers In Vivo.
Hoffman RM, Hoshiya Y, Guo W.
Methods Mol Biol. 2019;1866:75-81. doi: 10.1007/978-1-4939-8796-2_7.
PMID: 30725409
Abstract
Methionine (MET) dependence is the elevated requirement of cancer cells for MET. Cancer cells are arrested when MET is restricted in late S/G2 phase of the cell cycle. MET dependence may be the only known general metabolic defect in cancer. This chapter reviews the in vivo efficacy of dietary MET restriction (MR) to arrest human-cancer cell-line tumors and mouse tumors in nude mice. Human cancer xenografts in nude mice, when fed a MET-free diet, had greatly inhibited tumor growth. The body weight of mice on the MET-free diet was found to be maintainable by once-per-week administration of MET. These results suggested that MET dependence can be an important target for human cancer treatment. Yoshida sarcoma in nude mice on a MET-depleted diet regressed. MET depletion resulted in the extended survival of the tumor-bearing mice. These experiments are a prelude to further clinical studies of the efficacy of MR diets on cancer patients.
KEYWORDS:
Cell lines; Human cancer; Methionine dependence; Methionine-free diet; Nude mice; Sarcoma; Tumor growth inhibition; Yoshida sarcoma

Dietary Methionine Restriction-Based Cancer Chemotherapy in Rodents.
Hoffman RM, Stern PH.
Methods Mol Biol. 2019;1866:83-94. doi: 10.1007/978-1-4939-8796-2_8.
PMID: 30725410
Abstract
The elevated methionine (MET) requirement for the growth of tumors, first observed by Sugimura in 1959, termed MET dependence, is a potentially highly effective therapeutic target. Proof of this principle is that when MET restriction (MR) was initially established in co-cultures of cancer and normal cells, MET dependence could be exploited to selectively kill cancer cells without killing co-cultured normal cells. MET-dependent cells become reversibly blocked in the late S/G2 phase of the cell cycle under MR enabling selective and effective S-phase chemotherapy against these blocked cancer cells. Subsequent MET repletion with an anti-mitotic drug was totally effective at selectively eliminating the MET-dependent cancer cells enabling the normal MET-dependent cells to take over the culture. We have also observed that the MET analog ethionine (ETH) is synergistic with MR in arresting the growth of the Yoshida sarcoma both in vitro and eliminating metastasis when transplanted to nude mice. MR increased the efficacy of cisplatinum (CDDP) against the MX-1 human breast carcinoma cell line when grown in nude mice. MR increased 5-fluorouracil (5-FU) efficacy on a human gastric cancer xenograft, SC-1-NU, in nude mice. MET-restricted total parenteral nutrition (MR TPN) was effective in Yoshida sarcoma-bearing rats. MR TPN with doxorubicin (DOX) and vincristine (VCR) resulted in significant tumor suppression and prolonged survival of Yoshida-sarcoma-bearing rats. These results were the basis of subsequent studies that used methioninase to effect MR for effective cancer therapy.
KEYWORDS:
Cancer; Cell cycle; Cell cycle arrest; Chemotherapy; Diet; Methionine dependence; Methionine restriction; S/G2 phase; Total parenteral nutrition (TPN)

Clinical Studies of Methionine-Restricted Diets for Cancer Patients.
Hoffman RM.
Methods Mol Biol. 2019;1866:95-105. doi: 10.1007/978-1-4939-8796-2_9.
PMID: 30725411
Abstract
Methionine (MET) restriction (MR) has been shown to arrest cancer growth and sensitizes tumors to chemotherapy. MR total parenteral nutrition (MR TPN) with a chemotherapy-containing amino acid solution ("AO-90") (lacking both MET and L-cysteine[CYS]) showed synergistic effects with 5-fluorouracil (5-FU) in tumor-bearing rats and in a Phase I clinical trial with gastrointestinal tract cancers compared to 5-FU in a MET-containing TPN. All gastric cancer patients underwent gastrectomy. Resected tumors in the AO-90 group showed significant reduction of cancer histologically, while almost no effect was seen in the control group. A Phase II clinical trial of dietary MR combined with cystemustine treatment for melanoma or glioma was carried out. Twenty-two patients (20 with metastatic melanoma and 2 with recurrent gloma) received a median of four cycles of the combination of a 1-day MR diet with cystemustine (60 mg/m2) every 2 weeks. This combination was well tolerated (toxicity and nutritional status). The median disease-free survival was 1.8 months and the median survival was 4.6 months, with two long-duration stabilizations. MET depletion in plasma was 40%. In another study, eight patients with a variety of metastatic solid tumors were enrolled in a Phase I clinical trial of a commercially available MR medical food. Participants remained on the experimental diet for an average of 17.3 weeks. Plasma methionine levels fell from 21.6 to 9 μm within 2 weeks, a 58% decline. The only side effect was weight loss of approximately 0.5 kg per week. A feasibility study combining dietary MR with a FOLFOX regimen in patients with metastatic colorectal cancer was carried out. The plasma MET concentration was reduced by dietary MR by 58% on the first day of the MR diet. Among the four patients evaluable for response, three experienced a partial response and one patient had disease stabilization. The results of the above-described clinical trials indicate the clinical potential of MR.
KEYWORDS:
5-FU; 5-Fluorouracil; Cancer; Clinical trial; Gastric cancer; Histological response; MET-restricted TPN; Methionine (MET) dependence; Methionine restriction; Resection; Total parenteral nutrition (TPN)

Total Methionine Restriction Treatment of Cancer.
Hoffman RM, Kokkinakis DM, Frenkel EP.
Methods Mol Biol. 2019;1866:163-171. doi: 10.1007/978-1-4939-8796-2_13.
PMID: 30725415
Abstract
This chapter reviews how total methionine (MET) restriction (MR) of a human brain tumor xenograft, effected by the combination of recombinant L-methionine-α-deamino-γ-lyase (rMETase) and a MET-free diet, greatly potentiates standard chemotherapy for brain tumors in mouse models. The growth of human brain tumor Daoy, SWB77, and D-54 xenografts in nude mice was arrested after the depletion of mouse plasma methionine (MET) with a combination of an MR diet and rMETase and homocysteine to rescue normal cells and tissues. MET was depleted to below 5 μm by this treatment. MR for 10-12 days inhibited tumor growth, but did not prevent tumor regrowth after treatment cessation. A single dose of N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU), which was ineffective alone, was administered at the end of the MR regimen, and caused a more than 80-day growth delay for Daoy and D-54 and a 20-day growth delay for SWB77. The total MR treatment regimens also increased the efficacy of temozolomide (TMZ) against the SWB77 xenograft when administered at the end of the MET regimen.
KEYWORDS:
BCNU; Cancer; Choline; Combination; Homocysteine; Methionine; Methionine dependence; Nude mice; Recombinant methioninase; Rescue; Restriction; Temozolomide

Methionine Restriction and Life-Span Extension.
Hoffman RM.
Methods Mol Biol. 2019;1866:263-266. doi: 10.1007/978-1-4939-8796-2_19.
PMID: 30725421
Abstract
It has been known for almost a century that caloric restriction can extend the life span of rodents and many other types of animals. Approximately 25 years ago, it was found that a methionine-restricted (MR) diet could replace a caloric-restricted diet with the result of extending the life span of animals. This chapter summarizes the effects of MR on the reversal of diabetes, obesity, and other aspects of the metabolic syndrome, as well as extending the normal life span. The most effective way to restrict methionine in the body, using orally-delivered methioninase, is also explored.
KEYWORDS:
Aging; Diabetes; Life-span extension; Methioninase; Methionine restriction; Obesity; Oral delivery

Self-rated health (SRH) in young people and causes of death and mortality in young adulthood. A prospective registry-based Norwegian HUNT-study.
Vie TL, Hufthammer KO, Meland E, Breidablik HJ.
SSM Popul Health. 2019 Jan 23;7:100364. doi: 10.1016/j.ssmph.2019.100364. eCollection 2019 Apr.
PMID: 30723772
https://reader.elsevier.com/reader/sd/pii/S2352827318301587?token=039BB6292DFFA8AB8C04EAD52B00941B15B0CD9DF980E8F15596EDA6525676C69AF46A0E5B3B2B07AAB6CE93FF34CA9A
Abstract
BACKGROUND:
Self-rated health (SRH), which is frequently used in epidemiological research, has consistently been shown to be a strong predictor of morbidity and mortality, even after controlling for demographic, social and medical risk factors. However, less is known about the relationship between SRH and all-cause and cause-specific mortality in young adulthood.
OBJECTIVE:
To investigate SRH in young people (13-35 years-old) as a predictor of all-cause mortality in young adulthood (deaths before age 54) and examine the associated causes of death.
METHODS:
We used data from two large population-based cohort studies (N = 23,679): Young-HUNT1 (1995-1997, persons 13 to 20 years old, participation rate = 90%) and HUNT2 (1995-1997, persons 20 to 35 years old, participation rate = 70%). These data were linked to the Norwegian Cause of Death Registry up to 2014, and 247 deaths were identified. Other predictors we examined included age, gender, baseline smoking, physical activity and physical and mental disability.
RESULTS:
Participants reporting 'not so good'/'poor' SRH had approximately twice the risk of death compared to those reporting 'good' or 'very good' SRH at baseline. The association between low SRH and risk of death was attenuated when the models were adjusted for other predictors, but remained statistically significant. The causes of death differed somewhat between SRH levels. Most of the deaths for people reporting 'very good' SRH at baseline were mostly due to neoplasms (34%) and other external causes (30%). The causes of death were more varied for people reporting 'not so good'/'poor' SRH, with suicide (23%), other external causes (21%) and other/unknown causes of death (17%) being the most frequent causes.
CONCLUSION:
SRH predicts all-cause mortality in young adulthood, with poor SRH being associated with death in young adulthood. The findings also indicate different causes of death for different SRH. This knowledge is important for identifying groups at risk for later disease, which can potentially be used to prevent morbidity in the adult population.
KEYWORDS:
epidemiology; mortality; registry study; self-rated health; subjective health; young adulthood

Resolution of Hypothyroidism Restores Cold Induced Thermogenesis in Humans.
Maushart CI, Loeliger R, Gashi G, Christ-Crain M, Betz MJ.
Thyroid. 2019 Feb 6. doi: 10.1089/thy.2018.0436. [Epub ahead of print]
PMID: 30724123
Abstract
Objective Hypothyroidism is a frequent endocrine disorder with common symptoms of increased cold sensitivity and unintended weight gain, indicating changes in energy expenditure (EE) and response to cold exposure. Thyroid hormones (TH) play an important role for proper function of brown adipose tissue (BAT) and cold induced thermogenesis (CIT) in rodents, but the role of hypothyroidism on CIT in humans is uncertain. Methods This was a prospective observational study. We recruited 42 patients presenting with subclinical or overt hypothyroidism in whom TH replacement was planned. 33 patients completed the study. Thermogenesis was measured by indirect calorimetry during warm conditions and after a mild cold stimulus of 90 minutes, both during the hypothyroid state and after at least 3 months of sufficient TH replacement. CIT was determined as the difference between EE during mildly cold and warm conditions. The primary endpoint was the change of CIT between the hypothyroid and euthyroid state. Results EE during warm conditions increased from a median of 1330 (IQR 1251-1433) kcal/24h in the hypothyroid state to a median of 1442 (1294-1579) kcal/24h in the euthyroid state (+8.5%), p = 0.0002. EE during mild cold exposure increased from 1399 (1346-1571) kcal/24h to 1610 (1455-1674) kcal/24h (+15%), p <0.0001. The median CIT was 55 (1-128) kcal/24h at the baseline visit, after restoration of euthyroidism CIT increased by 102% to a median CIT of 111 (15.5-200) kcal/24h, p = 0.011. Serum levels of free thyroxine at the respective visit and mean outdoor temperature during the preceeding 30 days were significantly associated with CIT (p=0.021 and p=0.001, respectively). Conclusion Restoring euthyroidism significantly increases CIT in hypothyroid humans.

Disentangling the Effects of Monounsaturated Fat From Other Components of a Mediterranean Diet on Serum Metabolite Profiles: A Randomized Fully Controlled Dietary Intervention in Healthy Subjects at Risk of The Metabolic Syndrome.
Michielsen CCJR, Hangelbroek RWJ, Feskens EJM, Afman LA.
Mol Nutr Food Res. 2019 Feb 6:e1801095. doi: 10.1002/mnfr.201801095. [Epub ahead of print]
PMID: 30725537
https://sci-hub.tw/10.1002/mnfr.201801095
Abstract
SCOPE:
The Mediterranean (MED) diet is considered to be beneficial, however the contribution of the MUFA component in these beneficial effects is unclear. Therefore, we wanted to disentangle the effects of MUFA from the other components in a MED diet.
METHODS AND RESULTS:
We performed a randomized fully controlled parallel trial to examine the effects of the consumption of a saturated fatty acid (SFA)-rich diet, a MUFA-rich diet, or a MED diet for eight weeks on serum metabolome, in 47 subjects at risk of the metabolic syndrome. We assessed 162 serum metabolites before and after the intervention, by using a targeted NMR platform. 52 metabolites were changed during the intervention (FDR p<0.05). Both MUFA and MED diet decreased exactly the same fractions of LDL, including particle number, lipid, phospholipid and free cholesterol fraction (FDR p <0.05). The MED diet additionally decreased the larger subclasses of VLDL, several related VLDL fractions, VLDL-triglycerides, and serum-triglycerides (FDR p<0.05).
CONCLUSION:
Our findings clearly demonstrate that the MUFA component is responsible for reducing several LDL subclasses and fractions, and therefore causes a more anti-atherogenic lipid profile. Interestingly, consumption of the other components in the MED diet show additional health effects.
KEYWORDS:
circulating biomarkers; clinical trial; human; lipoprotein composition; metabolomics

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Breakfast Skipping and Type 2 Diabetes: Where Do We Stand?
Mekary RA.
J Nutr. 2019 Jan 1;149(1):1-3. doi: 10.1093/jn/nxy284. No abstract available.
PMID: 30624661
https://sci-hub.tw/10.1093/jn/nxy284

Breakfast Skipping Is Associated with Increased Risk of Type 2 Diabetes among Adults: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.
Ballon A, Neuenschwander M, Schlesinger S.
J Nutr. 2019 Jan 1;149(1):106-113. doi: 10.1093/jn/nxy194.
PMID: 30418612
Abstract
BACKGROUND:
Epidemiologic studies have indicated that breakfast skipping is associated with risk of type 2 diabetes. However, the shape of the dose-response relation and the influence of adiposity on this association have not been reported.
OBJECTIVE:
We investigated the association between breakfast skipping and risk of type 2 diabetes by considering the influence of the body mass index (BMI).
METHODS:
In this systematic review and meta-analysis, PubMed and Web of Science were searched up to August 2017. Prospective cohort studies on breakfast skipping and risk of type 2 diabetes in adults were included. Summary RRs and 95% CIs, without and with adjustment for BMI, were estimated with the use of a random-effects model in pairwise and dose-response meta-analyses.
RESULTS:
In total 6 studies, based on 96,175 participants and 4935 cases, were included. The summary RR for type 2 diabetes comparing ever with never skipping breakfast was 1.33 (95% CI: 1.22, 1.46, n = 6 studies) without adjustment for BMI, and 1.22 (95% CI: 1.12, 1.34, n = 4 studies) after adjustment for BMI. Nonlinear dose-response meta-analysis indicated that risk of type 2 diabetes increased with every additional day of breakfast skipping, but the curve reached a plateau at 4-5 d/wk, showing an increased risk of 55% (summary RR: 1.55; 95% CI: 1.41, 1.71). No further increase in risk of type 2 diabetes was observed after 5 d of breakfast skipping/wk (P for nonlinearity = 0.08).
CONCLUSIONS:
This meta-analysis provides evidence that breakfast skipping is associated with an increased risk of type 2 diabetes, and the association is partly mediated by BMI.

The Historical Context and Scientific Legacy of John O. Holloszy.
Hagberg JM, Coyle EF, Baldwin KM, Cartee GD, Fontana L, Joyner MJ, Kirwan JP, Seals DR, Weiss EP.
J Appl Physiol (1985). 2019 Feb 7. doi: 10.1152/japplphysiol.00669.2018. [Epub ahead of print]
PMID: 30730811
Abstract
John O. Holloszy, as perhaps the world's pre-eminent exercise biochemist/physiologist, published >400 papers over his 50+ year career and they have been cited >41,000 times. In 1965 Holloszy showed for the first time that exercise training in rodents resulted in a doubling of skeletal muscle mitochondria, ushering in a very active era of skeletal muscle plasticity research. He subsequently went on to describe the consequences of and the mechanisms underlying these adaptations. Holloszy was first to show that muscle contractions increase muscle glucose transport independent of insulin and he studied the mechanisms underlying this response throughout his career. He published important papers assessing the impact of training on glucose and insulin metabolism in healthy and diseased humans. Holloszy was at the forefront of rodent studies of caloric restriction and longevity in the 1980's, following these studies with important cross-sectional and longitudinal caloric restriction studies in humans. Holloszy was influential in the discipline of cardiovascular physiology, showing that older healthy and diseased populations could still elicit beneficial cardiovascular adaptations with exercise training. Holloszy and his group made important contributions to exercise physiology on the effects of training on numerous metabolic, hormonal, and cardiovascular adaptations. Holloszy's outstanding productivity was made possible by his mentoring of ~100 postdoctoral fellows and substantial NIH grant funding over his entire career. Many of these fellows have also played critical roles in the exercise physiology/biochemistry discipline. Thus, it is clear that exercise biochemistry and physiology will be influenced by John Holloszy for numerous years to come.
KEYWORDS:
aging; caloric restriction; diabetes; exercise training; skeletal muscle
>>>>>>>>>>>>>>>>>>>>>>>>>>>>
Obituary: John O. Holloszy, former director of applied physiology, 85
Considered the father of modern exercise biochemistry
by Jim Dryden
July 25, 2018
https://medicine.wustl.edu/news/obituary-john-o-holloszy-former-director-of-applied-physiology-85/

Low-Carbohydrate Diet Score and Macronutrient Intake in Relation to Survival After Colorectal Cancer Diagnosis.
Song M, Wu K, Meyerhardt JA, Yilmaz O, Wang M, Ogino S, Fuchs CS, Giovannucci EL, Chan AT.
JNCI Cancer Spectr. 2018 Nov;2(4):pky077. doi: 10.1093/jncics/pky077. Epub 2019 Jan 28.
PMID: 30734025
https://sci-hub.tw/10.1093/jncics/pky077
Abstract
BACKGROUND:
A low-carbohydrate diet may improve cancer survival, but relevant clinical evidence remains limited.
METHODS:
We followed 1542 stages I to III colorectal cancer (CRC) patients who completed a validated food frequency questionnaire between 6 months and 4 years after diagnosis. We calculated overall, animal-, and plant-rich, low-carbohydrate diet scores and examined their associations with CRC-specific and overall mortality using Cox proportional hazards regression after adjusting for potential predictors for cancer survival. We also assessed the intake and changes of macronutrients after diagnosis. Statistical tests were two-sided.
RESULTS:
Although no association was found for overall and animal-rich low-carbohydrate diet score, plant-rich, low-carbohydrate diet, which emphasizes plant sources of fat and protein with moderate consumption of animal products, was associated with lower CRC-specific mortality (hazard ratio {HR} comparing extreme quartiles = 0.37, 95% confidence interval [CI] = 0.25 to 0.57, P trend < .001). Carbohydrate intake was associated with higher CRC-specific mortality, and this association was restricted to carbohydrate consumed from refined starches and sugars (HR per one-SD increment = 1.36, 95% CI = 1.14 to 1.62, P trend < .001). In contrast, replacing carbohydrate with plant fat and protein was associated with lower CRC-specific mortality, with the HR per one-SD increment of 0.81 (95% CI = 0.69 to 0.95, P trend = .01) for plant fat and 0.77 (95% CI = 0.62 to 0.95, P trend = .02) for plant protein. Similar results were obtained for overall mortality and when changes in macronutrient intake after diagnosis were assessed.

CONCLUSION:
Plant-rich, low-carbohydrate diet score was associated with lower mortality in patients with nonmetastatic CRC. Substituting plant fat and protein for carbohydrate, particularly that from refined starches and sugars, may improve patients' survival.

Total cholesterol and all-cause mortality by sex and age: a prospective cohort study among 12.8 million adults.
Yi SW, Yi JJ, Ohrr H.
Sci Rep. 2019 Feb 7;9(1):1596. doi: 10.1038/s41598-018-38461-y.
PMID: 30733566
https://www.nature.com/articles/s41598-018-38461-y.pdf
Abstract
It is unclear whether associations between total cholesterol (TC) levels and all-cause mortality and the optimal TC ranges for lowest mortality vary by sex and age. 12,815,006 Korean adults underwent routine health examinations during 2001-2004, and were followed until 2013. During follow-up, 694,423 individuals died. U-curve associations were found. In the TC ranges of 50-199 and 200-449 mg/dL, each 39 mg/dL (1 mmol/L) increase in TC was associated with 23% lower (95% CI:23%,24%) and 7% higher (6%,7%) mortality, respectively. In the age groups of 18-34, 35-44, 45-54, 55-64, 65-74, and 75-99 years, each 1 mmol/L higher TC increased mortality by 14%, 13%, 8%, 7%, 6%, and 3%, respectively (P < 0.001 for each age group), for TC ≥ 200 mg/dL, while the corresponding TC changes decreased mortality by 13%, 27%, 34%, 31%, 20%, and 13%, respectively, in the range < 200 mg/dL (P < 0.001 for each age group). TC had U-curve associations with mortality in each age-sex group. TC levels associated with lowest mortality were 210-249 mg/dL, except for men aged 18-34 years (180-219 mg/dL) and women aged 18-34 years (160-199 mg/dL) and 35-44 years (180-219 mg/dL). The inverse associations for TC < 200 mg/dL were stronger than the positive associations in the upper range.

Effect of coenzyme Q10 supplementation on clinical features of migraine: a systematic review and dose-response meta-analysis of randomized controlled trials.
Parohan M, Sarraf P, Javanbakht MH, Ranji-Burachaloo S, Djalali M.
Nutr Neurosci. 2019 Feb 6:1-8. doi: 10.1080/1028415X.2019.1572940. [Epub ahead of print]
PMID: 30727862
Abstract
OBJECTIVE:
Coenzyme Q10 is an antioxidant and an essential mitochondrial cofactor which has been suggested to improve the clinical features of migraine. Several randomized clinical trials have examined the effects of Coenzyme Q10 on migraine with inconclusive results. The aim of this systematic review and meta-analysis was to evaluate the impact of Coenzyme Q10 supplementation on the frequency, severity, and duration of migraine attacks.
METHODS:
A systematic review of the literature was conducted using ISI Web of Science, PubMed, Cochrane library and Scopus to identify eligible studies up to April 2018. Studies included were randomized clinical trials of Coenzyme Q10 supplementation that reported the frequency, severity, or duration of migraine attacks as a primary outcome. A meta-analysis of eligible studies was performed using the fixed effects model or the random effects model to estimate pooled effect size.
RESULTS:
Four randomized clinical trials with 221 participants were included. Coenzyme Q10 supplementation significantly reduced the frequency of migraine attacks (weighted mean difference: -1.87 attacks/month, 95% CI: -2.69 to -1.05, p < 0.001) without significant heterogeneity among the studies (I2 = 36.6%, p = 0.192). Coenzyme Q10 supplementation had no significant effect on severity (weighted mean difference: -2.35 visual analog scale score, 95% CI: -5.19 to 0.49, p = 0.105) and duration of migraine attacks (weighted mean difference: -6.14 h, 95% CI: -13.14 to 0.87, p = 0.086) with high heterogeneity.
CONCLUSION:
Pooled analyses of available randomized clinical trials suggest that Coenzyme Q10 supplementation may reduce the frequency of migraine attacks per month without affecting the severity or duration of migraine attacks.
KEYWORDS:
Coenzyme Q10; meta-analysis; migraine; systematic review

Menopausal Hormone Therapy and Risk of Diverticulitis.
Jovani M, Ma W, Joshi AD, Liu PH, Nguyen LH, Cao Y, Tam I, Wu K, Giovannucci EL, Chan AT, Strate LL.
Am J Gastroenterol. 2019 Feb;114(2):315-321. doi: 10.14309/ajg.0000000000000054.
PMID: 30730324
Abstract
INTRODUCTION:
Diverticulitis is a significant cause of morbidity among older women, and little attention has been paid to understanding its etiology. We have shown that menopausal hormone therapy (MHT) is associated with the risk of inflammatory bowel disease. In this study, we prospectively examined the association between MHT and the risk of incident diverticulitis.
METHODS:
We studied 65,367 postmenopausal women enrolled in the Nurses' Health Study who provided detailed information on hormone use and other medical and lifestyle factors biennially, and on diet every 4 years. Between 2008 and 2014, participants reported any episodes of diverticulitis that required antibiotics and the date of occurrence. We used Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).
RESULTS:
Over 24 years encompassing 1,297,165 person-years of follow-up, we documented 5,425 incident cases of diverticulitis. We observed an increased risk of diverticulitis among both current (HR 1.28; 95% CI 1.18-1.39) and past (HR 1.35; 95% CI 1.25-1.45) MHT users compared to never users. The increased risk was observed among participants using estrogen only (HR 1.30; 95% CI 1.20-1.41) and those using combined estrogen and progesterone (HR 1.31; 95% CI 1.21-1.42) compared to nonusers. The risk did not increase with longer duration of use (P-trend = 0.76). The association between MHT and diverticulitis was not modified by age, body mass index, past oral contraceptive use, or fiber intake (all P-interaction >0.11).
CONCLUSIONS:
Menopausal hormone therapy was associated with an increased risk of diverticulitis. Further studies are needed to understand the potential mechanisms that may underlie this association.

Edited by AlPater

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Docosahexaenoic acid reduces resting blood pressure but increases muscle sympathetic outflow compared to eicosapentaenoic acid in healthy men and women.
Lee JB, Notay K, Klingel S, Chabowski A, Mutch DM, Millar PJ.
Am J Physiol Heart Circ Physiol. 2019 Feb 8. doi: 10.1152/ajpheart.00677.2018. [Epub ahead of print]
PMID: 30735073
Abstract
Supplementation with monounsaturated or omega-3 polyunsaturated fatty acids (n-3 PUFA) can lower resting blood pressure (BP) and reduce the risk of cardiovascular events. The independent contributions of n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on BP, and mechanisms responsible, are unclear. We tested whether EPA, DHA, and olive oil (OO), a source of monounsaturated fat, differentially affect resting hemodynamics and muscle sympathetic nerve activity (MSNA). Eighty-six healthy young men and women were recruited to participate in a 12-week, randomized, double-blind trial examining the effects of orally supplementing ~3g/day of EPA (n=28), DHA (n=28), or OO (n=30) on resting hemodynamics, and in a subset (n=31), MSNA. Both EPA and DHA supplements increased the Omega-3 Index ( P<0.01). Reductions in systolic BP were greater (adjusted intergroup mean difference [95% CI]) following DHA (-3.4 mmHg [-0.9,-5.9], p=0.008) and OO (-3.0 mmHg [-0.5,-5.4], P=0.01) compared to EPA, with no difference between DHA and OO ( P=0.74). Reductions in diastolic BP were greater following DHA (-3.4 mmHg [-1.3,-5.6], p=0.002) and OO (-2.2 mmHg [0.08,-4.3], P=0.04) compared to EPA. EPA increased heart rate compared to DHA (4.2 beats/min, [-0.009,8.4], P=0.05) and OO (4.2 beats/min, [0.08,8.3], P=0.04). MSNA burst frequency was higher following DHA (4 bursts/minute [0.5,8.3], p=0.02) but not OO (-3 bursts/minute [-6,0.6], P=0.2) compared to EPA. Overall, DHA and OO evoked similar responses in resting BP; however, DHA but not OO increased peripheral vasoconstrictor outflow. These findings may have implications for fatty acid supplementation in clinical populations characterized by chronic high BP and sympathetic over-activation.
KEYWORDS:
Blood pressure; Dietary Supplement; Omega-3 polyunsaturated fatty acids; Sympathetic nerve activity

Seasonal variation of diet quality in a large middle-aged and elderly Dutch population-based cohort.
van der Toorn JE, Cepeda M, Kiefte-de Jong JC, Franco OH, Voortman T, Schoufour JD.
Eur J Nutr. 2019 Feb 8. doi: 10.1007/s00394-019-01918-5. [Epub ahead of print]
PMID: 30734846
https://sci-hub.tw/10.1007/s00394-019-01918-5
Abstract
PURPOSE:
Several studies have reported seasonal variation in intake of food groups and certain nutrients. However, whether this could lead to a seasonal pattern of diet quality has not been addressed. We aimed to describe the seasonality of diet quality, and to examine the contribution of the food groups included in the dietary guidelines to this seasonality.
METHODS:
Among 9701 middle-aged and elderly participants of the Rotterdam Study, a prospective population-based cohort, diet was assessed using food-frequency questionnaires (FFQ). Diet quality was measured as adherence to the Dutch dietary guidelines, and expressed in a diet quality score ranging from 0 to 14 points. The seasonality of diet quality and of the food group intake was examined using cosinor linear mixed models. Models were adjusted for sex, age, cohort, energy intake, physical activity, body mass index, comorbidities, and education.
RESULTS:
Diet quality had a seasonal pattern with a winter-peak (seasonal variation = 0.10 points, December-peak) especially among participants who were men, obese and of high socio-economic level. This pattern was mostly explained by the seasonal variation in the intake of legumes (seasonal variation = 3.52 g/day, December-peak), nuts (seasonal variation = 0.78 g/day, January-peak), sugar-containing beverages (seasonal variation = 12.96 milliliters/day, June-peak), and dairy (seasonal variation = 17.52 g/day, June-peak).
CONCLUSIONS:
Diet quality varies seasonally with heterogeneous seasonality of food groups counteractively contributing to the seasonal pattern in diet quality. This seasonality should be considered in future research on dietary behavior. Also, season-specific recommendations and policies are required to improve diet quality throughout the year.
KEYWORDS:
Diet quality; Dietary guidelines; Food frequency questionnaire; Food groups; Seasonality

Physical activity modifies the effect of calcium supplements on bone loss in perimenopausal and postmenopausal women: subgroup analysis of a randomized controlled trial.
Nakamura K, Saito T, Kobayashi R, Oshiki R, Kitamura K, Watanabe Y.
Arch Osteoporos. 2019 Feb 8;14(1):17. doi: 10.1007/s11657-019-0575-4.
PMID: 30734085
https://sci-hub.tw/10.1007/s11657-019-0575-4
Abstract
We aimed to determine whether the effect of calcium supplements on bone metabolism is modified by physical activity (PA) through a subgroup analysis of an RCT. PA may be a favorable effect modifier of the association between calcium intake and bone loss in perimenopausal and postmenopausal women.
PURPOSE:
Physical exercise can potentially modify bone metabolism. Here we aimed to determine whether the effect of calcium supplements on bone metabolism is modified by physical activity (PA) through a subgroup analysis of a randomized, double-blind, placebo-controlled trial.
METHODS:
The trial was conducted over the course of 2 years, and participants were 450 healthy women between 50 and 75 years of age who were randomly assigned to three equally-sized (N = 150 each) groups (500 mg calcium, 250 mg calcium, and placebo). Levels of PA at baseline were evaluated by quantifying moderate (4 METs) and vigorous (6 METs) activities based on a 7-day activity recall, and the total MET-hours per week was calculated. Follow-up BMD examinations were conducted 2 years later. Two-year changes in BMD were compared between the intention-to-treat higher PA subgroup (≥ 10 MET-hours/week) and the lower PA subgroup (< 10 MET-hours/week).
RESULTS:
Of the 450 participants, 418 underwent follow-up BMD measurements. Regarding the lower PA subgroup, spinal BMD in the 500 mg/day calcium supplement group decreased significantly less (- 0.029 g/cm2, P = 0.042) than in the placebo group (- 0.045 g/cm2), and femoral neck BMD in the 500 mg/day calcium supplement group decreased significantly less (- 0.027 g/cm2, P = 0.049) than in the placebo group (- 0.038 g/cm2). In contrast, changes in neither spinal nor femoral neck BMD significantly differed between the three treatment groups in the higher PA subgroup.
CONCLUSIONS:
PA is a favorable effect modifier of the association between calcium intake and bone loss in perimenopausal and postmenopausal women with low calcium intake.
KEYWORDS:
Bone density; Calcium; Physical activity; Postmenopause; Randomized controlled trial

Coffee, tea, caffeine, and risk of non-melanoma skin cancer in a Chinese population: The Singapore Chinese Health Study.
Oh CC, Jin A, Yuan JM, Koh WP.
J Am Acad Dermatol. 2019 Feb 4. pii: S0190-9622(19)30195-1. doi: 10.1016/j.jaad.2019.01.084. [Epub ahead of print]
PMID: 30731173
Abstract
BACKGROUND:
While epidemiological studies in populations of European-descent suggest possible chemo-protective effect of caffeine against non-melanoma skin cancer (NMSC), data in Asian populations are lacking.
OBJECTIVES:
We examined the relations between coffee, tea and caffeine consumption, and NMSC risk among Chinese in Singapore.
METHODS:
We used data from the Singapore Chinese Health Study, a prospective cohort of 63,257 men and women aged 45-74 years at recruitment from 1993 to 1998. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazard models.
RESULTS:
Coffee drinking was associated with reduced NMSC risk in a dose-dependent manner (P trend<0.0001); compared with those who drank coffee less than weekly, in those who drank ≥3 cups/day, HRs (95% CIs) were 0.54 (0.31-0.93) for risk of basal cell carcinoma, and 0.33 (0.13-0.84) for risk of squamous cell carcinoma. Compared with non-drinkers, daily drinkers of black tea also had reduced NMSC risk (HR=0.70; 95% CI=0.52-0.94). Caffeine intake reduced NMSC risk in a stepwise manner (P trend=0.0025); subjects with caffeine intake ≥400 mg/day had the lowest risk (HR=0.59; 95% CI=0.34-1.04).
CONCLUSION:
Consumption of caffeinated drinks such as coffee and black tea may reduce the risk of NMSC among Chinese.
KEYWORDS:
Chinese; caffeine; coffee; non-melanoma skin cancer; tea

Comparative analysis of the gut microbiota in centenarians and young adults shows a common signature across genotypically non-related populations.
Tuikhar N, Keisam S, Labala RK, Imrat, Ramakrishnan P, Arunkumar MC, Ahmed G, Biagi E, Jeyaram K.
Mech Ageing Dev. 2019 Feb 6. pii: S0047-6374(18)30205-7. doi: 10.1016/j.mad.2019.02.001. [Epub ahead of print]
PMID: 30738080
Abstract
Gut microbiota is among the factors that may be involved in healthy aging. Broader and geographically spread studies on gut microbiota of centenarians can help in identifying a common signature of longevity. We identified an endogamous Indian population with high centenarian prevalence. Here, we compared the gut microbiota composition and fecal metabolites of a centenarians group (˜100 years) with young people (25-45 years) of the region with the high centenarian prevalence and the nearby region of low centenarian prevalence to decipher microbial-related longevity signatures. Also, we compared our results with publicly available datasets of similar groups including 125 centenarians from three countries (Italy, Japan, China). Our comparative analysis resulted in higher biodiversity within Ruminococcaceae in centenarians, with respect to younger adults, irrespective of their nationality. We observed bacterial signatures that are common among extremely old people of different nationality. Comparative metabolites profiling identified the fecal metabolic signature of extreme aging in the Indian study population. Our analysis of the co-occurrence network and bimodal distribution of several taxa suggested the establishment of a pervasive change in the gut ecology during extreme aging. Our study might pave the way to develop gut microbiota based biomarkers for healthy aging.
KEYWORDS:
Butyrate; Centenarians; Faecal metabolites; Gut microbiota; Longevity; Naga community; Ruminococcaceae

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Low-carbohydrate diets differing in carbohydrate restriction improve cardiometabolic and anthropometric markers in healthy adults: A randomised clinical trial.
Harvey CJDC, Schofield GM, Zinn C, Thornley SJ, Crofts C, Merien FLR.
PeerJ. 2019 Feb 5;7:e6273. doi: 10.7717/peerj.6273. eCollection 2019.
PMID: 30740270
https://peerj.com/articles/6273/
Abstract
BACKGROUND:
Low-carbohydrate, high-fat (LCHF) diets are useful for treating a range of health conditions, but there is little research evaluating the degree of carbohydrate restriction on outcome measures. This study compares anthropometric and cardiometabolic outcomes between differing carbohydrate-restricted diets.
OBJECTIVE:
Our hypothesis was that moderate carbohydrate restriction is easier to maintain and more effective for improving cardiometabolic health markers than greater restriction.
DESIGN:
A total of 77 healthy participants were randomised to a very low-carbohydrate ketogenic diet (VLCKD), low-carbohydrate diet (LCD), or moderate-low carbohydrate diet (MCD), containing 5%, 15% and 25% total energy from carbohydrate, respectively, for 12-weeks. Anthropometric and metabolic health measures were taken at baseline and at 12 weeks. Using ANOVA, both within and between-group outcomes were analysed.
RESULTS:
Of 77 participants, 39 (51%) completed the study. In these completers overall, significant reductions in weight and body mass index occurred ((mean change) 3.7 kg/m2; 95% confidence limits (CL): 3.8, 1.8), along with increases in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, (0.49 mmol/L; 95% CL; 0.06, 0.92; p = 0.03), and total cholesterol concentrations (0.11 mmol/L; 95% CL; 0.00, 0.23; p = 0.05). Triglyceride (TG) levels were reduced by 0.12 mmol/L (95% CL; -0.20, 0.02; p = 0.02). No significant changes occurred between groups. The largest improvements in high density lipoprotein cholesterol (HDL-c) and TG and anthropometric changes occurred for the VLCKD group.
CONCLUSIONS:
Low-carbohydrate, high-fat diets have a positive effect on markers of health. Adherence to the allocation of carbohydrate was more easily achieved in MCD, and LCD groups compared to VLCKD and there were comparable improvements in weight loss and waist circumference and greater improvements in HDL-c and TG with greater carbohydrate restriction.
KEYWORDS:
Adherence; Carbohydrate restriction; Cardiometabolic health; Diet; Ketogenic; LCHF; Low-carbohydrate; Nutrition

Associations of specific dietary protein with longitudinal insulin resistance, prediabetes and type 2 diabetes: The Rotterdam Study.
Chen Z, Franco OH, Lamballais S, Ikram MA, Schoufour JD, Muka T, Voortman T.
Clin Nutr. 2019 Jan 31. pii: S0261-5614(19)30040-8. doi: 10.1016/j.clnu.2019.01.021. [Epub ahead of print]
PMID: 30739809
https://sci-hub.tw/10.1016/j.clnu.2019.01.021
Abstract
BACKGROUND & AIMS:
High protein intake has been linked to increased type 2 diabetes (T2D) risk. However, if this association differs by protein from specific food sources, and if a habitual high protein intake affects insulin resistance and prediabetes risk are largely unknown. We aimed to investigate associations between protein intake from different food sources with longitudinal insulin resistance, and risk of prediabetes and T2D.
METHODS:
Our analyses included 6822 participants aged ≥45 years without diabetes at baseline in three sub-cohorts of the prospective population-based Rotterdam Study. We measured protein intake at baseline using food-frequency questionnaires. Data on longitudinal homeostatic model assessment of insulin resistance (HOMA-IR), and incidence of prediabetes and T2D were available from 1993 to 2014.
RESULTS:
During follow-up, we documented 931 prediabetes cases and 643 T2D cases. After adjusting for sociodemographic, lifestyle, and dietary factors, higher total protein intake was associated with higher longitudinal HOMA-IR and with higher risk of prediabetes and T2D (per 5% increment in energy from protein at the expense of carbohydrate, for HOMA-IR: β = 0.10, (95%CI 0.07, 0.12); for prediabetes: HR = 1.34 (1.24 1.44); for T2D: HR = 1.37 (1.26, 1.49)). These associations were mainly driven by total animal protein (for HOMA-IR: 0.10 (0.07, 0.12); for prediabetes: 1.35 (1.24, 1.45); for T2D: 1.37 (1.26; 1.49)). The harmful associations of total animal protein were contributed to by protein from meat, fish, and dairy (e.g. for HOMA-IR: protein from meat, 0.13 (0.10, 0.17); from fish, 0.08 (0.03, 0.13); from dairy, 0.04 (0.0003, 0.08)). After additional adjustment for longitudinal waist circumference, associations of total protein and total animal protein with longitudinal HOMA-IR and prediabetes risk were attenuated, but remained statistically significant. Total plant protein, as well as protein from legumes and nuts, from grains, from potatoes, or from fruits and vegetables, was not associated with any of the outcomes.
CONCLUSIONS:
Higher intake of animal protein, from meat, dairy and fish food sources, is associated with higher longitudinal insulin resistance and risk of prediabetes and T2D, which may be partly mediated by obesity over time. Furthermore, plant protein from different sources is not related to insulin resistance, and risk of prediabetes and T2D. Our findings highlight the importance of specific protein food sources and that habitual high animal protein intake may already in early stages be harmful in the development of T2D.
KEYWORDS:
Animal protein intake; Insulin resistance; Plant protein intake; Prediabetes; Protein intake; Type 2 diabetes

Stage 1 hypertension, but not elevated blood pressure, predicts 10-year fatal and non-fatal CVD events in healthy adults: the ATTICA Study.
Critselis E, Chrysohoou C, Kollia N, Georgousopoulou EN, Tousoulis D, Pitsavos C, Panagiotakos DB; ATTICA Study group.
J Hum Hypertens. 2019 Feb 11. doi: 10.1038/s41371-019-0169-z. [Epub ahead of print]
PMID: 30742050
https://sci-hub.tw/10.1038/s41371-019-0169-z
Abstract
The study evaluated the extent to which high normal blood pressure (HNBP), elevated BP, and Stage 1 hypertension predict 10-year incidence of cardiovascular disease (CVD). A population-based, prospective cohort study was conducted among 3042 randomly selected Greek adults, aged 18-89 years. Following 10-years follow-up (2002-2012), incidence of non-fatal and fatal CVD (ICD-10) was achieved in 2020 participants. The analytic sample (n = 1403) excluded hypertensive patients. At baseline, the prevalence rate of HNBP, elevated BP, and Stage 1 hypertension was 44.6% (n = 626), 29.0% (n = 408), and 15.5% (n = 218), respectively. During follow-up, the 10-year combined (fatal or non-fatal) CVD incidence rates in HNBP, elevated BP, and Stage 1 hypertensive individuals were 15.6% (n = 98), 12.0% (n = 49), and 22.5% (n = 49), respectively, as compared to 6.3% (n = 49) in normotensives (all p's < 0.0001). As compared to normotensives (and following the adjustment for known demographic, lifestyle and clinical confounding factors), HNBP participants had a 1.5-fold (Adjusted Hazard Ratio, Adj. HR: 1.49; 95% CI: 1.00-2.20) increased risk of 10-year CVD events. Similarly, Stage 1 hypertensive participants had an approximately twofold (Adj. HR: 1.90; 95% CI: 1.16-3.08) increased risk for 10-year CVD, particularly among males (Adj. HR: 2.03; 95% CI: 1.08-3.83). However, individuals with elevated BP did not exhibit a differential risk for developing 10-year CVD events (Adj. HR: 1.28; 95% CI: 0.82-2.02). Therefore, since HNBP and Stage 1 hypertension individuals exhibit a notable increased risk of 10-year fatal and non-fatal CVD, the implementation of targeted primary and secondary prevention interventions may deter both CVD and related adverse health outcomes.

Association Between Ultraprocessed Food Consumption and Risk of Mortality Among Middle-aged Adults in France.
Schnabel L, Kesse-Guyot E, Allès B, Touvier M, Srour B, Hercberg S, Buscail C, Julia C.
JAMA Intern Med. 2019 Feb 11. doi: 10.1001/jamainternmed.2018.7289. [Epub ahead of print]
PMID: 30742202
https://sci-hub.tw/10.1001/jamainternmed.2018.7289
Abstract
IMPORTANCE:
Growing evidence indicates that higher intake of ultraprocessed foods is associated with higher incidence of noncommunicable diseases. However, to date, the association between ultraprocessed foods consumption and mortality risk has never been investigated.
OBJECTIVE:
To assess the association between ultraprocessed foods consumption and all-cause mortality risk.
DESIGN, SETTING, AND PARTICIPANTS:
This observational prospective cohort study selected adults, 45 years or older, from the French NutriNet-Santé Study, an ongoing cohort study that launched on May 11, 2009, and performed a follow-up through December 15, 2017 (a median of 7.1 years). Participants were selected if they completed at least 1 set of 3 web-based 24-hour dietary records during their first 2 years of follow-up. Self-reported data were collected at baseline, including sociodemographic, lifestyle, physical activity, weight and height, and anthropometrics.
EXPOSURES:
The ultraprocessed foods group (from the NOVA food classification system), characterized as ready-to-eat or -heat formulations made mostly from ingredients usually combined with additives. Proportion (in weight) of ultraprocessed foods in the diet was computed for each participant.
MAIN OUTCOMES AND MEASURES:
The association between proportion of ultraprocessed foods and overall mortality was the main outcome. Mean dietary intakes from all of the 24-hour dietary records available during the first 2 years of follow-up were calculated and considered as the baseline usual food-and-drink intakes. Mortality was assessed using CépiDC, the French national registry of specific mortality causes. Hazard ratios (HRs) and 95% CIs were determined for all-cause mortality, using multivariable Cox proportional hazards regression models, with age as the underlying time metric.
RESULTS:
A total of 44 551 participants were included, of whom 32 549 (73.1%) were women, with a mean (SD) age at baseline of 56.7 (7.5) years. Ultraprocessed foods accounted for a mean (SD) proportion of 14.4% (7.6%) of the weight of total food consumed, corresponding to a mean (SD) proportion of 29.1% (10.9%) of total energy intake. Ultraprocessed foods consumption was associated with younger age (45-64 years, mean [SE] proportion of food in weight, 14.50% [0.04%]; P < .001), lower income (<€1200/mo, 15.58% [0.11%]; P < .001), lower educational level (no diploma or primary school, 15.50% [0.16%]; P < .001), living alone (15.02% [0.07%]; P < .001), higher body mass index (calculated as weight in kilograms divided by height in meters squared; ≥30, 15.98% [0.11%]; P < .001), and lower physical activity level (15.56% [0.08%]; P < .001). A total of 602 deaths (1.4%) occurred during follow-up. After adjustment for a range of confounding factors, an increase in the proportion of ultraprocessed foods consumed was associated with a higher risk of all-cause mortality (HR per 10% increment, 1.14; 95% CI, 1.04-1.27; P = .008).
CONCLUSIONS AND RELEVANCE:
An increase in ultraprocessed foods consumption appears to be associated with an overall higher mortality risk among this adult population; further prospective studies are needed to confirm these findings and to disentangle the various mechanisms by which ultraprocessed foods may affect health.

Fitness and Body Mass Index During Adolescence and Disability Later in Life: A Cohort Study.
Henriksson P, Henriksson H, Tynelius P, Berglind D, Löf M, Lee IM, Shiroma EJ, Ortega FB.
Ann Intern Med. 2019 Feb 12. doi: 10.7326/M18-1861. [Epub ahead of print]
PMID: 30743265
Abstract
BACKGROUND:
Low physical fitness, obesity, and the combination of the two in adolescence may be related to risk for disability in adulthood, but this has rarely been studied.
OBJECTIVE:
To examine individual and combined associations of cardiorespiratory fitness and obesity in male adolescents with later receipt of a disability pension due to all and specific causes.
DESIGN:
Population-based cohort study.
SETTING:
Sweden.
PARTICIPANTS:
1 079 128 Swedish adolescents aged 16 to 19 years who were conscripted into the military between 1972 and 1994.
MEASUREMENTS:
Cardiorespiratory fitness and body mass index (BMI) were measured at conscription and were related to information on later receipt of a disability pension obtained from the Social Insurance Agency.
RESULTS:
Over a median follow-up of 28.3 years, 54 304 men were granted a disability pension. Low cardiorespiratory fitness was strongly associated with later receipt of a disability pension due to all causes (hazard ratio, 3.74 [95% CI, 3.55 to 3.95] for lowest vs. highest fitness decile) and specific causes (psychiatric, musculoskeletal, injuries, nervous system, circulatory, and tumors). Obesity was associated with greater risk for receipt of a disability pension due to all and specific causes, with the greatest risks observed for class II and III obesity. Compared with being unfit, being moderately or highly fit was associated with attenuated risk for receipt of a disability pension across BMI categories.
LIMITATION:
The cohort did not include women, had data on smoking and alcohol intake only in a subsample, and lacked repeated measures of exposures and covariates.
CONCLUSION:
Low cardiorespiratory fitness, obesity, and the combination of the two were strongly associated with later chronic disability due to a wide range of diseases and causes. Although additional well-designed studies are required, these findings support the importance of high cardiorespiratory fitness and healthy body weight during adolescence to prevent later chronic disease.

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Redox parameters as markers of the rate of aging and predictors of lifespan.
Martínez de Toda I, Vida C, Garrido A, De la Fuente M.
J Gerontol A Biol Sci Med Sci. 2019 Feb 11. doi: 10.1093/gerona/glz033. [Epub ahead of print]
PMID: 30753310
Abstract
Oxidative stress has been reported to increase with aging and although several age-related changes in redox parameters have been described, none of them have been verified as markers of the rate of aging and lifespan. Therefore, antioxidant (catalase, glutathione peroxidase and reductase activities and reduced glutathione) and oxidant (oxidized glutathione, basal superoxide anion and malondialdehyde concentrations) parameters were studied in whole blood cells from humans divided into different age groups (adult, mature, elderly, nonagenarian and centenarian) in a cross-sectional study. Moreover, the same parameters were investigated in peritoneal leukocytes of mice at the analogous human ages (adult, mature, old, very old and long-lived) in a longitudinal study as well as in adult prematurely aging mice (PAM). The results reveal that the age-related alterations of these markers are similar in humans and mice, with decreased antioxidants and increased oxidants in old subjects whereas long-lived individuals show similar values to those in adults. Additionally, adult PAM showed similar values to those in chronologically old mice and had a shorter lifespan than non-prematurely aging mice. Thus, these parameters could be proposed as markers of the rate of aging and used to ascertain biological age in humans.

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Conjugated Linoleic Acid Effects on Cancer, Obesity, and Atherosclerosis: A Review of Pre-Clinical and Human Trials with Current Perspectives.
den Hartigh LJ.
Nutrients. 2019 Feb 11;11(2). pii: E370. doi: 10.3390/nu11020370. Review.
PMID: 30754681
[pdf availed from https://www.mdpi.com/2072-6643/11/2/370 site.]
Abstract
Obesity and its comorbidities, including type 2 diabetes and cardiovascular disease, are straining our healthcare system, necessitating the development of novel strategies for weight loss. Lifestyle modifications, such as exercise and caloric restriction, have proven effective against obesity in the short term, yet obesity persists because of the high predilection for weight regain. Therefore, alternative approaches to achieve long term sustainable weight loss are urgently needed. Conjugated linoleic acid (CLA), a fatty acid found naturally in ruminant animal food products, has been identified as a potential anti-obesogenic agent, with substantial efficacy in mice, and modest efficacy in obese human populations. Originally described as an anti-carcinogenic fatty acid, in addition to its anti-obesogenic effects, CLA has now been shown to possess anti-atherosclerotic properties. This review summarizes the pre-clinical and human studies conducted using CLA to date, which collectively suggest that CLA has efficacy against cancer, obesity, and atherosclerosis. In addition, the potential mechanisms for the many integrative physiological effects of CLA supplementation will be discussed in detail, including an introduction to the gut microbiota as a potential mediator of CLA effects on obesity and atherosclerosis.
KEYWORDS:
atherosclerosis; cancer; conjugated linoleic acid (CLA); diabetes; gut microbiota; obesity

The Role of the Microbiome in Cancer Initiation and Progression: How Microbes and Cancer Cells Utilize Excess Energy and Promote One Another's Growth.
Whisner
Curr Nutr Rep. 2019 Feb 13. doi: 10.1007/s13668-019-0257-2. [Epub ahead of print] Review.
PMID: 30758778
https://sci-hub.tw/10.1007/s13668-019-0257-2
Abstract
PURPOSE OF REVIEW:
We use an ecological lens to understand how microbes and cancer cells coevolve inside the ecosystems of our bodies. We describe how microbe-cancer cell interactions contribute to cancer progression, including cooperation between microbes and cancer cells. We discuss the role of the immune system in preventing this apparent 'collusion' and describe how microbe-cancer cell interactions lead to opportunities and challenges in treating cancer.
RECENT FINDINGS:
Microbiota influence many aspects of our health including our cancer risk. Since both microbes and cancer cells rely on incoming resources for their survival and replication, excess energy and nutrient input from the host can play a role in cancer initiation and progression. Certain microbes enhance cancer cell fitness by promoting proliferation and protecting cancer cells from the immune system. How diet influences these interactions remains largely unknown but recent evidence suggests a role for nutrients across the cancer continuum.
KEYWORDS:
Caloric restriction; Cancer; Cell proliferation; Diet; Ecology; Immune system; Inflammation; Metastasis; Microbe; Microbiome; Microbiota; Neoplasms; Neoplastic processes; Nutrition; Western diet

Meals with Similar Fat Content from Different Dairy Products Induce Different Postprandial Triglyceride Responses in Healthy Adults: A Randomized Controlled Cross-Over Trial.
Hansson P, Holven KB, Øyri LKL, Brekke HK, Biong AS, Gjevestad GO, Raza GS, Herzig KH, Thoresen M, Ulven SM.
J Nutr. 2019 Feb 13. doi: 10.1093/jn/nxy291. [Epub ahead of print]
PMID: 30759235
https://sci-hub.tw/10.1093/jn/nxy291
Abstract
BACKGROUND:
Postprandial lipemia is a risk factor for cardiovascular disease. Dairy products differ in nutrient content and food matrix, and little is known about how different dairy products affect postprandial triglyceride (TG) concentrations.
OBJECTIVE:
We investigated the effect of meals with similar amounts of fat from different dairy products on postprandial TG concentrations over 6 h in healthy adults.
METHODS:
A randomized controlled cross-over study was performed on 47 subjects (30% men), with median (25th-75th percentile) age of 32 (25-46) y and body mass index of 23.6 (21.0-25.8) kg/m2. Meals included 1 of butter, cheese, whipped cream, or sour cream, corresponding to 45 g of fat (approximately 60 energy%). Serum concentrations of TGs (primary outcome), and total cholesterol (TC), low density lipoprotein cholesterol (LDL cholesterol), high density lipoprotein cholesterol (HDL cholesterol), insulin, glucose, non-esterified fatty acids, and plasma glucose-dependent insulinotropic polypeptide (secondary outcomes) were measured before the meal and 2, 4, and 6 h postprandially. Incremental AUC (iAUC) was calculated for the responses, and data were analyzed using a linear mixed model.
RESULTS:
Sour cream induced a 61% larger TG-iAUC0-6 h compared to whipped cream (P < 0.001), a 53% larger TG-iAUC0-6 h compared to butter (P < 0.001), and a 23% larger TG-iAUC0-6 h compared to cheese (P = 0.05). No differences in TG-iAUC0-6 h between the other meals were observed. Intake of sour cream induced a larger HDL cholesterol-iAUC0-6 h compared to cheese (P = 0.01). Intake of cheese induced a 124% larger insulin iAUC0-6 h compared to butter (P = 0.006). No other meal effects were observed.
CONCLUSIONS:
High-fat meals containing similar amount of fat from different dairy products induce different postprandial effects on serum TGs, HDL cholesterol, and insulin in healthy adults. The potential mechanisms and clinical impact of our findings remain to be further elucidated.

Dietary total antioxidant capacity and mortality from all causes, cardiovascular disease and cancer: a systematic review and dose-response meta-analysis of prospective cohort studies.
Parohan M, Anjom-Shoae J, Nasiri M, Khodadost M, Khatibi SR, Sadeghi O.
Eur J Nutr. 2019 Feb 11. doi: 10.1007/s00394-019-01922-9. [Epub ahead of print] Review.
PMID: 30756144
Abstract
PURPOSE:
No conclusive information is available about the association between dietary total antioxidant capacity (DTAC) and risk of mortality. Current meta-analysis of prospective cohort studies was done to summarize available findings on the association between DTAC and risk of death from all-cause, cancer and cardiovascular diseases (CVDs).
METHODS:
Online databases were searched to detect relevant publications up to January 2018, using relevant keywords. To pool data, either fixed-effects or random-effects model was used. Furthermore, linear and non-linear dose-response analyses were also done.
RESULTS:
In total, five prospective studies were included in the current systematic review and meta-analysis. In a follow-up period of 4.3-16.5 years, there were 38,449 deaths from all-cause, 4470 from cancer and 2841 from CVDs among 226,297 individuals. A significant inverse association was found between DTAC and all-cause mortality (combined effect size: 0.62, 95% CI 0.60-0.64). Such finding was also seen for cancer (combined effect size: 0.81, 95% CI 0.75-0.88) and CVD (combined effect size: 0.71, 95% CI 0.63-0.82) mortality. Findings from linear dose-response meta-analysis revealed that a 5 mmol/day increment in DTAC based on ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) was associated with 7% and 15% lower risk of all-cause mortality, respectively. Based on findings from non-linear dose-response meta-analysis, a significant reduction in risk of all-cause mortality was seen when increasing FRAP from 2 to 12 mmol/day (P-nonlinearity = 0.002) and ORAC from 5 to 11 mmol/day (P-nonlinearity < 0.001).
CONCLUSIONS:
Adherence to diet with high total antioxidant capacity was associated with decreased risk of death from all-cause, cancer and CVDs.
KEYWORDS:
Antioxidants; Cancer; Cardiovascular; Dose–response; Meta-analysis; Mortality

Folic acid supplementation enhances arsenic methylation: results from a folic acid and creatine supplementation randomized controlled trial in Bangladesh.
Bozack AK, Hall MN, Liu X, Ilievski V, Lomax-Luu AM, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV.
Am J Clin Nutr. 2019 Feb 1;109(2):380-391. doi: 10.1093/ajcn/nqy148.
PMID: 30590411
Abstract
BACKGROUND:
Arsenic exposure through drinking water persists in many regions. Inorganic As (InAs) is methylated to monomethyl-arsenical species (MMAs) and dimethyl-arsenical species (DMAs), facilitating urinary excretion. Arsenic methylation is dependent on one-carbon metabolism, which is influenced by nutritional factors such as folate and creatine.
OBJECTIVE:
This study investigated the effects of folic acid (FA) and/or creatine supplementation on the proportion of As metabolites in urine.
DESIGN:
In a 24-wk randomized, double-blinded, placebo-controlled trial, 622 participants were assigned to receive FA (400 or 800 μg per day), 3 g creatine per day, 400 μg FA + 3 g creatine per day, or placebo. The majority of participants were folate sufficient; all received As-removal water filters. From wk 12-24, half of the participants receiving FA received placebo.
RESULTS:
Among groups receiving FA, the mean decrease in ln(%InAs) and %MMAs and increase in %DMAs exceeded those of the placebo group at wk 6 and 12 (P < 0.05). In the creatine group, the mean decrease in %MMAs exceeded that of the placebo group at wk 6 and 12 (P < 0.05); creatine supplementation did not affect change in %InAs or %DMAs. The decrease in %MMAs at wk 6 and 12 was larger in the 800 µg FA than in the 400 µg FA group (P = 0.034). There were no differences in treatment effects between the 400 µg FA and creatine + FA groups. Data suggest a rebound in As metabolite proportions after FA cessation; at wk 24, log(%InAs) and %DMAs were not significantly different than baseline levels among participants who discontinued FA supplementation.
CONCLUSIONS:
The results of this study confirm that FA supplementation rapidly and significantly increases methylation of InAs to DMAs. Further research is needed to understand the strong cross-sectional associations between urinary creatinine and As methylation in previous studies.

The effect of nuts on markers of glycemic control: a systematic review and meta-analysis of randomized controlled trials.
Tindall AM, Johnston EA, Kris-Etherton PM, Petersen KS.
Am J Clin Nutr. 2019 Feb 1;109(2):297-314. doi: 10.1093/ajcn/nqy236.
PMID: 30722007
Abstract
BACKGROUND:
Observational evidence suggests higher nut consumption is associated with better glycemic control; however, it is unclear if this association is causal.
OBJECTIVES:
We aimed to conduct a systematic review and meta-analysis of randomized controlled trials to examine the effect of tree nuts and peanuts on markers of glycemic control in adults.
METHODS:
A systematic review and meta-analysis of randomized controlled trials was conducted. A total of 1063 potentially eligible articles were screened in duplicate. From these articles, 40 were eligible for inclusion and data from these articles were extracted in duplicate. The weighted mean difference (WMD) between the nut intervention and control arms was determined for fasting glucose, fasting insulin, glycated hemoglobin (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR) using the DerSimonian and Laird random-effects method. For outcomes where a limited number of studies were published, a qualitative synthesis was presented.
RESULTS:
A total of 40 randomized controlled trials including 2832 unique participants, with a median duration of 3 mo (range: 1-12 mo), were included. Overall consumption of tree nuts or peanuts had a favorable effect on HOMA-IR (WMD: -0.23; 95% CI: -0.40, -0.06; I2 = 51.7%) and fasting insulin (WMD: -0.40 μIU/mL; 95% CI: -0.73, -0.07 μIU/mL; I2 = 49.4%). There was no significant effect of nut consumption on fasting blood glucose (WMD: -0.52 mg/dL; 95% CI: -1.43, 0.38 mg/dL; I2 = 53.4%) or HbA1c (WMD: 0.02%; 95% CI: -0.01%, 0.04%; I2 = 51.0%).
CONCLUSIONS:
Consumption of peanuts or tree nuts significantly decreased HOMA-IR and fasting insulin; there was no effect of nut consumption on HbA1c or fasting glucose. The results suggest that nut consumption may improve insulin sensitivity. In the future, well-designed clinical trials are required to elucidate the mechanisms that account for these observed effects.

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The exceptional longevity of the naked mole-rat may be explained by mitochondrial antioxidant defenses.
Munro D, Baldy C, Pamenter ME, Treberg JR.
Aging Cell. 2019 Feb 15:e12916. doi: 10.1111/acel.12916. [Epub ahead of print]
PMID: 30768748
Abstract
Naked mole-rats (NMRs) are mouse-sized mammals that exhibit an exceptionally long lifespan (>30 vs. <4 years for mice), and resist aging-related pathologies such as cardiovascular and pulmonary diseases, cancer, and neurodegeneration. However, the mechanisms underlying this exceptional longevity and disease resistance remain poorly understood. The oxidative stress theory of aging posits that (a) senescence results from the accumulation of oxidative damage inflicted by reactive oxygen species (ROS) of mitochondrial origin, and (b) mitochondria of long-lived species produce less ROS than do mitochondria of short-lived species. However, comparative studies over the past 28 years have produced equivocal results supporting this latter prediction. We hypothesized that, rather than differences in ROS generation, the capacity of mitochondria to consume ROS might distinguish long-lived species from short-lived species. To test this hypothesis, we compared mitochondrial production and consumption of hydrogen peroxide (H2 O2 ; as a proxy of overall ROS metabolism) between NMR and mouse skeletal muscle and heart. We found that the two species had comparable rates of mitochondrial H2 O2 generation in both tissues; however, the capacity of mitochondria to consume ROS was markedly greater in NMRs. Specifically, maximal observed consumption rates were approximately two and fivefold greater in NMRs than in mice, for skeletal muscle and heart, respectively. Our results indicate that differences in matrix ROS detoxification capacity between species may contribute to their divergence in lifespan.
KEYWORDS:
Heterocephalus glaber ; antioxidants; mitochondria; reactive oxygen species; skeletal muscle heart

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Influence of Eating Schedule on the Postprandial Response: Gender Differences.
Masihy M, Monrroy H, Borghi G, Pribic T, Galan C, Nieto A, Accarino A, Azpiroz F.
Nutrients. 2019 Feb 14;11(2). pii: E401. doi: 10.3390/nu11020401.
PMID: 30769861
https://www.mdpi.com/2072-6643/11/2/401/htm
Abstract
Ingestion of a meal induces conscious sensations depending of the characteristics of the meal and the predisposition of the eater. We hypothesized that the eating schedule plays a conditioning role, specifically, that an extemporaneous meal is less rewarding than when eaten at the habitual schedule. We conducted a randomized parallel trial in 10 women and 10 men comparing the responses to a consistent savoury lunch-type meal (stewed beans) eaten at the habitual afternoon schedule or at an unconventional time in the morning. Schedule and gender differences were analyzed by repeated measures analysis of covariance. In women, the sensory experience induced by the probe meal, particularly postprandial satisfaction, was weaker when eaten at an unconventional time for breakfast. Men were resilient to the schedule effect and experienced the same sensations regardless of the timing of ingestion; the effect of the eating schedule was significantly more pronounced in women for fullness (F(1,55) = 14.9; p < 0.001), digestive well-being (F(1,36.8) = 22.3; p < 0.001), mood (F(1,12.4) = 13.8; p < 0.001), and anxiety (F(1,11.9) = 10.9; p = 0.001). No differences in the physiological responses induced by the afternoon and morning meals were detected either in women or men. Our data indicate that women are more susceptible to changes in meal schedule than men.
KEYWORDS:
eating habits; gender differences; hedonic response; homeostatic responses; meal ingestion; meal schedule; postprandial sensations

Searching Tardigrades for Lifesaving Secrets
Researchers are drawing inspiration from the proteins that they think let hearty water bears cheat time by decelerating their biology.
Tardigrades have special proteins that scientists believe help them achieve suspended animation.
By Steph Yin
Feb. 15, 2019
https://www.nytimes.com/2019/02/15/health/tardigrades-suspended-animation.html

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Influence of genetic polymorphisms and habitual caffeine intake on the changes in blood pressure, pulse rate, and calculation speed after caffeine intake: A prospective, double blind, randomized trial in healthy volunteers.
Yoshihara T, Zaitsu M, Shiraishi F, Arima H, Takahashi-Yanaga F, Arioka M, Kajioka S, Sasaguri T.
J Pharmacol Sci. 2019 Feb 1. pii: S1347-8613(19)30011-8. doi: 10.1016/j.jphs.2019.01.006. [Epub ahead of print]
PMID: 30773300
https://reader.elsevier.com/reader/sd/pii/S1347861319300118?token=186FBFAA7DE77CAE70F8110EF18B9BB41E8DB1583DDB42B5439CB6D1A3BBE6FC8DE780979B1B0DA274292395896C2BA2
Abstract
The aim of this study was to investigate the contribution of gene polymorphisms, in combination with habitual caffeine consumption, to the effect of caffeine intake on hemodynamic and psychoactive parameters. A double-blind, prospective study was conducted with 201 healthy volunteers randomly allocated 2:1 to the caffeinated group (150 mL decaffeinated coffee with additional 200 mg caffeine) or decaffeinated group (150 mL decaffeinated coffee). We measured the changes in blood pressure (BP) and calculation speed upon coffee intake, stratifying with gene polymorphisms, e.g., those in adenosine A2A receptor (ADORA2A) and cytochrome P450 (CYP) 1A2, and daily caffeine consumption (≤90 mg/day and >90 mg/day). Overall, caffeine intake independently increased BP and calculation speed (p-values < 0.05), irrespective of the polymorphisms. In stratified analysis, a statistical significance within the caffeinated group was observed for the change in systolic BP in the stratum of CYP1A2 polymorphism with daily caffeine consumption ≤90 mg/day: change in systolic BP in the CYP1A2 rs762551 CC group (mean ± SD = 11.8 ± 5.9) was higher than that in the AA/CA group (4.1 ± 5.5). Gene polymorphisms may limitedly modify the effect of caffeine intake on hemodynamic parameters in combination with habitual caffeine consumption.
KEYWORDS:
ADORA2A; Blood pressure; CYP1A2; Caffeine; Polymorphism

Dietary exposure to polychlorinated biphenyls and risk of heart failure - A population-based prospective cohort study.
Åkesson A, Donat-Vargas C, Berglund M, Glynn A, Wolk A, Kippler M.
Environ Int. 2019 Feb 15;126:1-6. doi: 10.1016/j.envint.2019.01.069. [Epub ahead of print]
PMID: 30776745
Abstract
BACKGROUND:
Beneficial effects of fish consumption on heart failure (HF) may be modified by contaminants in fish. Polychlorinated biphenyls (PCBs) are of particular concern as they have been associated with well-established risk factors of HF, but current data are limited.
OBJECTIVES:
We aimed to assess the association between dietary PCB exposure and risk of HF, accounting for dietary intake of long-chain omega-3 fish fatty acids.
DESIGN:
We used the prospective population-based research structure SIMPLER (previously the Swedish Mammography Cohort and Cohort of Swedish Men) comprising 32,952 women and 36,546 men, free from cancer, cardiovascular disease and diabetes at baseline in 1997. Validated estimates of dietary PCBs and long-chain omega-3 fish fatty acids [eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)] were obtained via a food frequency questionnaire at baseline. Incident cases of HF were ascertained through register linkage.
RESULTS:
During an average of 12 years of follow-up, we ascertained 2736 and 3128 incident cases of HF in women and men, respectively. In multivariable-adjusted models, mutually adjusted for PCBs and EPA-DHA, the relative risk (RR) for dietary PCB exposure was 1.48 (95% CI 1.12-1.96) in women and 1.42 (95% CI 1.08-1.86) in men, comparing extreme quintiles. Corresponding RRs for EPA-DHA intake were 0.71 (95% CI 0.54-0.93) and 0.82 (95% CI 0.63-1.07), respectively.
CONCLUSIONS:
Dietary exposure to PCBs was associated with an increased risk of HF in both women and men. EPA-DHA intake was associated with a lower risk of HF in women, with a similar tendency in men.
KEYWORDS:
Fish; Heart failure; Long-chain omega-3 fish fatty acids; Polychlorinated biphenyls

Primary and secondary prevention of preterm birth: a review of systematic reviews and ongoing randomized controlled trials.
Matei A, Saccone G, Vogel JP, Armson AB.
Eur J Obstet Gynecol Reprod Biol. 2019 Jan 25. pii: S0301-2115(18)31153-9. doi: 10.1016/j.ejogrb.2018.12.022. [Epub ahead of print] Review.
PMID: 30772047
Abstract
BACKGROUND:
Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality. Interventions aimed at preventing PTB can be classified as primary, secondary, or tertiary prevention.
OBJECTIVE:
To conduct a review of systematic reviews on the effectiveness and safety of primary and secondary preterm birth prevention interventions.
SEARCH STRATEGY:
A systematic literature search of the Cochrane, PubMed/Medline, EMBASE and CINAHL databases was conducted on 2 September 2015, and updated on 21 November 2016.
SELECTION CRITERIA:
We included any published systematic review of randomized controlled trials (RCTs) or individual patient data (IPD) of RCTs related to primary or secondary prevention of PTB, published between 2005-2016 where gestational age at birth (of any interval) was a pre-specified outcome. Individual trials and non-systematic reviews were not eligible.
DATA COLLECTION AND ANALYSIS:
The population of interest was all pregnant women, regardless of PTB risk. The primary outcome was PTB < 37 weeks.
MAIN RESULTS:
In total, 112 reviews were included in this study. Overall there were 49 Cochrane and 63 non-Cochrane reviews. Eight were individual participant data (IPD) reviews. Sixty reviews assessed the effect of primary prevention interventions on risk of PTB. Positive effects were reported for lifestyle and behavioural changes (including diet and exercise); nutritional supplements (including calcium and zinc supplementation); nutritional education; screening for lower genital tract infections. Eighty-three systematic reviews were identified relating to secondary PTB prevention interventions. Positive effects were found for low dose aspirin among women at risk of preeclampsia; clindamycin for treatment of bacterial vaginosis; treatment of vaginal candidiasis; progesterone in women with prior spontaneous PTB and in those with short midtrimester cervical length; L-arginine in women at risk for preeclampsia; levothyroxine among women with tyroid disease; calcium supplementation in women at risk of hypertensive disorders; smoking cessation; cervical length screening in women with history of PTB with placement of cerclage in those with short cervix; cervical pessary in singleton gestations with short cervix; and treatment of periodontal disease.
CONCLUSION:
The overview serves as a guide to current evidence relevant to PTB prevention. Only a few interventions have been demononstrated to be effective, including cerclage, progesterone, low dose aspirin, and lifestyle and behavioural changes. For several of the interventions evaluated, there was insufficient evidence to assess whether they were effective or not.
KEYWORDS:
Neonatal; Obstetrics; Prematurity; Preterm birth; Prevention

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Nutrient Sensing, Signaling and Ageing: The Role of IGF-1 and mTOR in Ageing and Age-Related Disease.
Johnson SC.
Subcell Biochem. 2018;90:49-97. doi: 10.1007/978-981-13-2835-0_3.
PMID: 30779006
Abstract
Nutrient signaling through insulin/IGF-1 was the first pathway demonstrated to regulate ageing and age-related disease in model organisms. Pharmacological or dietary interventions targeting nutrient signaling pathways have been shown to robustly attenuate ageing in many organisms. Caloric restriction, the most widely studied longevity promoting intervention, works through multiple nutrient signaling pathways, while inhibition of mTOR through treatment with rapamycin reproducibly delays ageing and disease through specific inhibition of the mTOR complexes. Although the benefits of reduced insulin/IGF-1 in lifespan and health are well documented in model organisms, defining the precise role of the IGF-1 in human ageing and age-related disease has proven more difficult. Association studies provide some insight but also reveal paradoxes. Low serum IGF-1 predicts longevity, but IGF-1 decreases with age and IGF-1 therapy benefits some of age-related pathologies. Circulating IGF-1 has been associated both positively and negatively with risk of age-related diseases in humans, and in some cases both activation and inhibition of IGF-1 signaling have provided benefit in animal models of the same diseases. Interventions designed modulate the nutrient sensing signaling pathways positively or negatively are already available for clinical use, highlighting the need for a clear understanding of the role of nutrient signaling in ageing and age-related disease. This chapter examines data from model organisms and human genetic association studies, with a special emphasis on IGF-1 and mTOR, and discusses potential models for resolving the paradoxes surrounding IGF-1 data.
KEYWORDS:
Ageing; IGF-1; Nutrient signaling; PI3K; mTOR

Nutrition and Ageing.
Malcomson FC, Mathers JC.
Subcell Biochem. 2018;90:373-424. doi: 10.1007/978-981-13-2835-0_13.
PMID: 30779016
Abstract
The ageing trajectory is plastic and can be slowed down by lifestyle factors, including good nutrition, adequate physical activity and avoidance of smoking. In humans, plant-based diets such as the Mediterranean dietary pattern are associated with healthier ageing and lower risk of age-related disease, whereas obesity accelerates ageing and increases the likelihood of most common complex diseases including CVD, T2D, dementia, musculoskeletal diseases and several cancers. As yet, there is only weak evidence in humans about the molecular mechanisms through which dietary factors modulate ageing but evidence from cell systems and animal models suggest that it is probable that better dietary choices influence all 9 hallmarks of ageing. It seems likely that better eating patterns retard ageing in at least two ways including (i) by reducing pervasive damaging processes such as inflammation, oxidative stress/redox changes and metabolic stress and (ii) by enhancing cellular capacities for damage management and repair. From a societal perspective, there is an urgent imperative to discover, and to implement, cost-effective lifestyle (especially dietary) interventions which enable each of us to age well, i.e. to remain physically and socially active and independent and to minimise the period towards the end of life when individuals suffer from frailty and multi-morbidity.
KEYWORDS:
Dietary energy restriction; Dietary patterns; Hallmarks of ageing; Mediterranean diet; Plant-based diets

Midlife moderation-quantified healthy diet and 40-year mortality risk from CHD: the prospective National Heart, Lung, and Blood Institute Twin Study.
Dai J, Krasnow RE, Reed T.
Br J Nutr. 2016 Jul;116(2):326-34. doi: 10.1017/S0007114516001914. Epub 2016 May 18.
PMID: 27188259 Free PMC Article
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5897114/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5897114/pdf/nihms931460.pdf
Abstract
It is unknown whether influences of midlife whole diet on the long-term CHD mortality risk are independent of genetic and common environmental factors or familial predisposition. We addressed this question prospectively using data from the National Heart, Lung, and Blood Institute Twin Study. We included 910 male twins who were middle-aged and had usual diet assessed with nutritionist-administered, cross-checked dietary history interview at baseline (1969-1973). Moderation-quantified healthy diet (MQHD), a dietary pattern, was created to evaluate a whole diet. Primary outcome was time-to-CHD death. Hazard ratios (HR) were estimated using frailty survival model. Known CHD risk factors were controlled. During the follow-up of 40 years through 31 December 2009, 113 CHD deaths, 198 total cardiovascular deaths and 610 all-cause deaths occurred. In the entire cohort, the multivariable-adjusted HR for the overall association (equivalent to a general population association) was 0·76 (95 % CI 0·66, 0·88) per 10-unit increment in the MQHD score for CHD, and the multivariable-adjusted HR for a twin with a MQHD score ten units higher than his co-twin brother was 0·79 (95 % CI 0·64, 0·96, P=0·02) for CHD independent of familial predisposition. Similar results were found for a slightly more food-specified alternative moderation-quantified healthy diet (aMQHD). The between-pair association (reflecting familial influence) was significant for CHD for both MQHD and aMQHD. It is concluded that associations of MQHD and aMQHD with a lower long-term CHD mortality risk are both nutritionally and familially affected, supporting their use for dietary planning to prevent CHD mortality.
KEYWORDS:
CHD; DZ dizygotic; Diets; HR hazard ratio; MQHD modified Mediterranean-style diet; MZ monozygotic; Mortality; Twin studies; aMQHD alternative modified Mediterranean-style diet

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