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Anthropometric changes and risk of diabetes: are there sex differences? A longitudinal study of Alberta's Tomorrow Project.
Ye M, Robson PJ, Eurich DT, Vena JE, Xu JY, Johnson JA.
BMJ Open. 2019 Jul 19;9(7):e023829. doi: 10.1136/bmjopen-2018-023829.
PMID: 31326923
https://bmjopen.bmj.com/content/bmjopen/9/7/e023829.full.pdf
Abstract
OBJECTIVES:
To characterise the sex-specific difference in the association between anthropometric changes and risk of diabetes in the general population in Canada.
SETTING AND PARTICIPANTS:
From 2000 to 2008, Alberta's Tomorrow Project (ATP) invited Alberta's residents aged 35-69 years to a prospective cohort study. A total of 19 655 diabetes-free ATP participants having anthropometrics measured at the baseline and follow-ups were included.
DESIGN AND OUTCOME MEASURES:
A longitudinal study design was used to examine the association between anthropometric changes and risk of diabetes and the sex difference in this association. Changes in weight, body mass index (BMI), waist circumference (WC) and waist-hip-ratio (WHR) were calculated as the difference between baseline and follow-up measures. Diabetes cases were identified using the Canadian National Diabetes Surveillance System algorithm with administrative healthcare data (2000-2015) linked to the ATP cohort. The sex-specific association between anthropometric changes and incidence of diabetes were examined by multivariable Cox regression models.
RESULTS:
Changes in weight, BMI, WC and WHR over time were positively associated with incidence of diabetes in both men and women. The sex difference in risk of diabetes associated with 1 standard deviation (SD) increase in anthropometrics was 0.07 (95% CI -0.02 to 0.14) for weight, 0.08 (95% CI -0.03 to 0.17) for BMI, 0.07 (95% CI -0.02 to 0.15) for WC and 0.09 (95% CI 0.03 to 0.13) for WHR. Similar results were found in sex difference in the associations with changes per 5% and changes per categories (5% loss, ±5%, 5% gain).
CONCLUSIONS:
The positive association between anthropometric changes and risk of diabetes was generally stronger in men than in women. However, this sex-specific difference of approximately 10% of the total risk associated with anthropometric changes had limited significance. For population-based public health programmes aiming to control obesity and incidence of diabetes, it may not be necessary to set up sex-specific goals for anthropometric reduction.
KEYWORDS:
Alberta’s Tomorrow Project; anthropometric changes; diabetes; longitudinal study; sex difference

Substitution of dietary protein sources in relation to colorectal cancer risk in the NIH-AARP cohort study.
Liao LM, Loftfield E, Etemadi A, Graubard BI, Sinha R.
Cancer Causes Control. 2019 Jul 20. doi: 10.1007/s10552-019-01210-1. [Epub ahead of print]
PMID: 31327110
https://sci-hub.tw/10.1007/s10552-019-01210-1
Abstract
PURPOSE:
To evaluate the substitution effect of plant for animal protein with risk of CRC in the large prospective National Institutes of Health-AARP cohort study.
METHODS:
Protein intake was assessed at baseline using a food frequency questionnaire. HRs and 95% CIs were estimated using multivariable adjusted hazard ratios from Cox proportional hazards models. We used a substitution model with total protein intake held constant, so that an increase in plant protein was offset by an equal decrease in animal protein.
RESULTS:
Among 489,625 individuals, we identified 8,995 incident CRCs after a median follow-up of 15.5 years. Substituting plant protein for animal protein was associated with a reduced risk of CRC (HR for highest vs. lowest fifth 0.91; 95% CI 0.83-0.99). This reduction in CRC risk appeared to be primarily due to substituting plant protein for red meat protein (HR 0.89; 95% CI 0.81-0.97), not white meat protein (HR 0.96; 95% CI 0.88-1.05) or other animal protein (HR 0.94; 95% CI 0.86-1.03). When further evaluated by source, reduction in CRC risk was limited to the substitution of protein from bread, cereal, and pasta for red meat protein (HR 0.86; 95% CI 0.80-0.93); this association was stronger for distal colon (HR 0.78; 95% CI 0.67-0.90) and rectal cancer (HR 0.79; 95% CI 0.68-0.91) but null for proximal colon (HR 0.99; 95% CI 0.88-1.11).
CONCLUSIONS:
This study shows that substituting plant protein for animal protein, especially red meat protein, is associated with a reduced risk of CRC, and suggests that protein source impacts CRC risk.

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Association Between Plant-Based Dietary Patterns and Risk of Type 2 Diabetes: A Systematic Review and Meta-analysis.
Qian F, Liu G, Hu FB, Bhupathiraju SN, Sun Q.
JAMA Intern Med. 2019 Jul 22. doi: 10.1001/jamainternmed.2019.2195. [Epub ahead of print]
PMID: 31329220
https://sci-hub.tw/10.1001/jamainternmed.2019.2195
Abstract
IMPORTANCE:
Accumulating epidemiologic evidence has suggested favorable associations between plant-based dietary patterns and risk of type 2 diabetes, although there is a lack of a quantitative summary of evidence substantiating this important association.
OBJECTIVE:
To quantitatively synthesize available prospective observational evidence on the association between plant-based dietary patterns and risk of type 2 diabetes.
DATA SOURCES:
A systematic search of PubMed and MEDLINE, Embase, Web of Science, and reference lists through February 15, 2019, was conducted. Data analysis was conducted between December 2018 and February 2019.
STUDY SELECTION:
All prospective observational studies that examined the association between adherence to plant-based dietary patterns and incidence of type 2 diabetes among adults 18 years or older were identified.
DATA EXTRACTION AND SYNTHESIS:
Meta-analysis of Observational Studies in Epidemiology guidelines for data abstraction and reporting were followed, and a National Heart, Lung, and Blood Institute assessment tool was used to evaluate study quality. Two authors independently conducted full-text assessments and data abstraction. Meta-analysis was conducted using the random-effects method to calculate the overall relative risk (RR) and 95% CI.
MAIN OUTCOMES AND MEASURES:
Level of adherence to a plant-based diet and incidence of type 2 diabetes.
RESULTS:
A total of 9 studies were identified, totaling 307 099 participants with 23 544 cases of incident type 2 diabetes. A significant inverse association was observed between higher adherence to a plant-based dietary pattern and risk of type 2 diabetes (RR, 0.77; 95% CI, 0.71-0.84) in comparison with poorer adherence, with modest heterogeneity across studies (I2 = 44.5%; P = .07 for heterogeneity). Similar findings were obtained when using the fixed-effects model (RR, 0.80; 95% CI, 0.75-0.84). Consistent associations were observed across predefined subgroups. This association was strengthened when healthy plant-based foods, such as fruits, vegetables, whole grains, legumes, and nuts, were included in the definition of plant-based patterns (RR, 0.70; 95% CI, 0.62-0.79). Most studies were deemed to have good quality in terms of dietary assessment, disease outcomes, and statistical adjustment for confounding factors. Using restricted cubic splines, a significant inverse linear dose-response association was identified between plant-based dietary indices and risk of type 2 diabetes.
CONCLUSIONS AND RELEVANCE:
Plant-based dietary patterns, especially when they are enriched with healthful plant-based foods, may be beneficial for the primary prevention of type 2 diabetes.

Dietary fats, blood pressure and artery health.
DiNicolantonio JJ, OKeefe J.
Open Heart. 2019 Jun 25;6(1):e001035. doi: 10.1136/openhrt-2019-001035. eCollection 2019. No abstract available.
PMID: 31328005
https://openheart.bmj.com/content/openhrt/6/1/e001035.full.pdf

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Solving the mystery of the weight-loss plateau
Releasing the brakes on fat burning in humans without altering many other functions an important question
Kelly Crowe · CBC News · Posted: Jul 23, 2019
https://www.cbc.ca/news/health/second-opinion190720-1.5220887

Heterogeneity of healthy aging: comparing long-lived families across five healthy aging phenotypes of blood pressure, memory, pulmonary function, grip strength, and metabolism.
Marron MM, Wojczynski MK, Minster RL, Boudreau RM, Sebastiani P, Cosentino S, Thyagarajan B, Ukraintseva SV, Schupf N, Christensen K, Feitosa M, Perls T, Zmuda JM, Newman AB; Long Life Family Study.
Geroscience. 2019 Jul 22. doi: 10.1007/s11357-019-00086-y. [Epub ahead of print]
PMID: 31332674
Abstract
Five healthy aging phenotypes were developed in the Long Life Family Study to uncover longevity pathways and determine if healthy aging across multiple systems clustered in a subset of long-lived families. Using blood pressure, memory, pulmonary function, grip strength, and metabolic measures (body mass index, waist circumference and fasting levels of glucose, insulin, triglycerides, lipids, and inflammatory markers), offspring were ranked according to relative health using gender-, age-, and relevant confounder-adjusted z-scores. Based on our prior work, families met a healthy aging phenotype if ≥ 2 and ≥ 50% of their offspring were exceptionally healthy for that respective phenotype. Among 426 families, only two families met criteria for three healthy aging phenotypes and none met criteria for four or more healthy aging phenotypes. Using Spearman correlation, the proportion of offspring within families with exceptionally healthy pulmonary function was correlated with the proportion of offspring within families with exceptional strength (r = 0.19, p = 0.002). The proportion of offspring within families meeting the healthy blood pressure and metabolic phenotypes were also correlated (r = 0.14, p = 0.006), and more families were classified as meeting healthy blood pressure and metabolic phenotypes (Kappa = 0.10, p = 0.02), as well as the healthy pulmonary and blood pressure phenotypes than expected by chance (Kappa = 0.09, p = 0.03). Other phenotypes were weakly correlated (|r| ≤ 0.07) with low pairwise agreement (Kappa ≤ 0.06). Among these families selected for familial longevity, correspondence between healthy aging phenotypes was weak, supporting the heterogeneous nature of longevity and suggesting biological underpinnings of each individual phenotype should be examined separately to determine their shared and unique determinants.
KEYWORDS:
Familial longevity; Healthy aging

Intake of fibre and plant foods and the risk of abdominal aortic aneurysm in a large prospective cohort study in Sweden.
Bergwall S, Acosta S, Sonestedt E.
Eur J Nutr. 2019 Jul 22. doi: 10.1007/s00394-019-02054-w. [Epub ahead of print]
PMID: 31332505
Abstract
PURPOSE:
The purpose of this study was to investigate fibre, and plant foods, and its association with AAA risk.
METHODS:
In this prospective cohort study, Malmö Diet and Cancer Study, baseline data collection was carried out 1991-1996. The study participants' (n = 26,133) dietary habits were extensively recorded at baseline. The specific diagnosis of AAA in the in-hospital registry was found valid in 95%. The association between plant foods, such as cereals and types of vegetables, and AAA was assessed by using Cox regression analysis expressed as hazard ratios (HR) with 95% confidence intervals (CI).
RESULTS:
A high intake of fibre was independently associated with AAA risk (HR per quintile 0.87, 95% CI 0.79-0.97). High intake of vegetables (HR 0.91, 95% CI 0.84-0.98), specifically leaf vegetables (HR 0.87, 95% CI 0.81-0.94), and fruits and berries (HR 0.89, 95% CI 0.82-0.96), citrus (HR 0.91, 95% CI 0.85-0.98) and non-citrus fruits (HR 0.87, 95% CI 0.81-0.95) were independently associated with a decreased AAA risk.
CONCLUSIONS:
A high intake of fruits and berries and vegetables, in particular leaf vegetables, are associated with a decreased risk of developing AAA.
KEYWORDS:
Abdominal aortic aneurysm; Diet; Fibre; Fruits; Prospective study; Vegetables

Citrus Consumption and Risk of Cutaneous Malignant Melanoma in the Women's Health Initiative.
Melough MM, Wu S, Li WQ, Eaton C, Nan H, Snetselaar L, Wallace R, Qureshi AA, Cho E, Chun OK.
Nutr Cancer. 2019 Jul 23:1-8. doi: 10.1080/01635581.2019.1644353. [Epub ahead of print]
PMID: 31335211
Abstract
Citrus products are rich sources of furocoumarins, a class of photoactive compounds. Certain furocoumarins combined with ultraviolet radiation can induce skin cancer. We examined the relationship between citrus consumption and cutaneous melanoma risk among 56,205 Caucasian postmenopausal women in the Women's Health Initiative. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of melanoma by citrus intake level. During a mean follow-up of 15.7 years, 956 incident melanoma cases were documented. In multivariable adjusted models, the HR (95% CI) for melanoma was 1.12 (0.91, 1.37) among the highest citrus consumers (1.5+ servings/day of fruit or juice) versus the lowest (<2 servings/week), 0.95 (0.76, 1.20) among the highest citrus fruit consumers (5+ servings/week) versus non-consumers, and was 1.13 (0.96, 1.32) for the highest citrus juice consumers (1+ servings/day) versus the lowest (<1 serving/week). In stratified analyses, an increased melanoma risk associated with citrus juice intake was observed among women who spent the most time outdoors in summer as adults; the HR for the highest versus lowest intake was 1.22 (1.02, 1.46) (p trend = 0.03). Further research is needed to explore the association of melanoma with citrus juices among women with high sun exposure.

Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study.
Lipnicki DM, Makkar SR, Crawford JD, Thalamuthu A, Kochan NA, Lima-Costa MF, Castro-Costa E, Ferri CP, Brayne C, Stephan B, Llibre-Rodriguez JJ, Llibre-Guerra JJ, Valhuerdi-Cepero AJ, Lipton RB, Katz MJ, Derby CA, Ritchie K, Ancelin ML, Carrière I, Scarmeas N, Yannakoulia M, Hadjigeorgiou GM, Lam L, Chan WC, Fung A, Guaita A, Vaccaro R, Davin A, Kim KW, Han JW, Suh SW, Riedel-Heller SG, Roehr S, Pabst A, van Boxtel M, Köhler S, Deckers K, Ganguli M, Jacobsen EP, Hughes TF, Anstey KJ, Cherbuin N, Haan MN, Aiello AE, Dang K, Kumagai S, Chen T, Narazaki K, Ng TP, Gao Q, Nyunt MSZ, Scazufca M, Brodaty H, Numbers K, Trollor JN, Meguro K, Yamaguchi S, Ishii H, Lobo A, Lopez-Anton R, Santabárbara J, Leung Y, Lo JW, Popovic G, Sachdev PS; for Cohort Studies of Memory in an International Consortium (COSMIC).
PLoS Med. 2019 Jul 23;16(7):e1002853. doi: 10.1371/journal.pmed.1002853. eCollection 2019 Jul.
PMID: 31335910
Abstract
BACKGROUND:
With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups.
METHODS AND FINDINGS:
We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife.
CONCLUSIONS:
These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.

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Early Time-Restricted Feeding Reduces Appetite and Increases Fat Oxidation But Does Not Affect Energy Expenditure in Humans.
Ravussin E, Beyl RA, Poggiogalle E, Hsia DS, Peterson CM.
Obesity (Silver Spring). 2019 Aug;27(8):1244-1254. doi: 10.1002/oby.22518.
PMID: 31339000
Abstract
OBJECTIVE:
Eating earlier in the daytime to align with circadian rhythms in metabolism enhances weight loss. However, it is unknown whether these benefits are mediated through increased energy expenditure or decreased food intake. Therefore, this study performed the first randomized trial to determine how meal timing affects 24-hour energy metabolism when food intake and meal frequency are matched.
METHODS:
Eleven adults with overweight practiced both early time-restricted feeding (eTRF) (eating from 8 am to 2 pm) and a control schedule (eating from 8 am to 8 pm) for 4 days each. On the fourth day, 24-hour energy expenditure and substrate oxidation were measured by whole-room indirect calorimetry, in conjunction with appetite and metabolic hormones.
RESULTS:
eTRF did not affect 24-hour energy expenditure (Δ = 10 ± 16 kcal/d; P = 0.55). Despite the longer daily fast (intermittent fasting), eTRF decreased mean ghrelin levels by 32 ± 10 pg/mL (P = 0.006), made hunger more even-keeled (P = 0.006), and tended to increase fullness (P = 0.06-0.10) and decrease the desire to eat (P = 0.08). eTRF also increased metabolic flexibility (P = 0.0006) and decreased the 24-hour nonprotein respiratory quotient (Δ = -0.021 ± 0.010; P = 0.05).
CONCLUSIONS:
Meal-timing interventions facilitate weight loss primarily by decreasing appetite rather than by increasing energy expenditure. eTRF may also increase fat loss by increasing fat oxidation.

Associations of self-reported stair climbing with all-cause and cardiovascular mortality: The Harvard Alumni Health Study.
Rey-Lopez JP, Stamatakis E, Mackey M, Sesso HD, Lee IM.
Prev Med Rep. 2019 Jun 28;15:100938. doi: 10.1016/j.pmedr.2019.100938. eCollection 2019 Sep.
PMID: 31338282
https://reader.elsevier.com/reader/sd/pii/S2211335519301123?token=00842E7CBB1794206AC1E241F0221349782F39F300DE2AB5832444F7B2CFE32798AB174FFE1C1C3744A9EBF5662E6DC9
Abstract
To evaluate the association between numbers of floors climbed (per week) and all-cause and cardiovascular (CVD) mortality in men. A prospective study was conducted in 8874 men (Median [interquartile range] age: 65 years [60-71.6 years]) from the Harvard Alumni Health Study. Participants reported the number of floors habitually climbed, physical activity in their leisure time, other health related behaviours and any physician diagnosed disease in 1988. Men were followed for mortality through December 2008. Multivariate Cox hazard models to examine the association between weekly number of floors climbed and all-cause and CVD mortality adjusted for participation in total physical activity and other confounders. During a median follow-up of 12.4 years, 4063 men died (1195 from CVD). After adjusting for confounders (age, walking, sports/recreation, body mass index, alcohol intake, and smoking, diagnoses of hypertension or diabetes or high cholesterol) number of stairs habitually climbed was inversely associated with all-cause mortality (p trend <0.001). Compared with the group who climbed <10 floors/week, the hazard ratio (HR) for the ≥35 floors/week group was 0.84 95% confidence interval (CI) (0.78-0.91). In contrast, we found no evidence for an association between stair climbing and CVD mortality risk (p trend = 0.38), in the ≥35 floors/week group: HR = 0.94 95%CI (0.81-1.09). In this cohort of older men, stair climbing was associated with a lower risk of mortality from any causes. Further insights may be gained from future observational studies utilizing emerging pattern recognition of stair climbing from objective measurements of physical activity.
KEYWORDS:
Epidemiology; Exercise; Movement; Physical activity; Prospective

Association of Normal-Weight Central Obesity With All-Cause and Cause-Specific Mortality Among Postmenopausal Women.
Sun Y, Liu B, Snetselaar LG, Wallace RB, Caan BJ, Rohan TE, Neuhouser ML, Shadyab AH, Chlebowski RT, Manson JE, Bao W.
JAMA Netw Open. 2019 Jul 3;2(7):e197337. doi: 10.1001/jamanetworkopen.2019.7337.
PMID: 31339542
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2738622
Abstract
IMPORTANCE:
Current public health guidelines for obesity prevention and control focus on promoting a normal body mass index (BMI), rarely addressing central obesity, which is reflected by high waist circumference (WC) and common in the general population. Studies of the association of normal-weight central obesity with long-term health outcomes are sparse.
OBJECTIVE:
To examine associations of normal-weight central obesity with all-cause and cause-specific mortality in postmenopausal women in the United States.
DESIGN, SETTING, AND PARTICIPANTS:
A nationwide prospective cohort study of 156 624 postmenopausal women enrolled in the Women's Health Initiative at 40 clinical centers in the United States between 1993 and 1998. These women were observed through February 2017. Data analysis was performed from September 15, 2017, to March 13, 2019.
EXPOSURES:
Different combinations of BMI (calculated as weight in kilograms divided by height in meters squared; normal weight: BMI, 18.5-24.9; overweight: BMI, 25.0-29.9; and obesity: BMI, ≥30) and WC (normal: WC, ≤88 cm and high: WC, >88 cm).
MAIN OUTCOMES AND MEASURES:
Mortality from all causes, cardiovascular disease, and cancer.
RESULTS:
Of the 156 624 women (mean [SD] age, 63.2 [7.2] years), during 2 811 187 person-years of follow-up, 43 838 deaths occurred, including 12 965 deaths from cardiovascular disease (29.6%) and 11 828 deaths from cancer (27.0%). Compared with women with normal weight and no central obesity and adjusted for demographic characteristics, socioeconomic status, lifestyle factors, and hormone use, the hazard ratio for all-cause mortality was 1.31 (95% CI, 1.20-1.42) among women with normal weight and central obesity, 0.91 (95% CI, 0.89-0.94) among women with overweight and no central obesity, 1.16 (95% CI, 1.13-1.20) for women with overweight and central obesity, 0.93 (95% CI, 0.89-0.94) for women with obesity and no central obesity, and 1.30 (95% CI, 1.27-1.34) for women with obesity and central obesity. Compared with normal weight without central obesity, normal-weight central obesity was associated with higher risk of cardiovascular disease mortality (hazard ratio, 1.25; 95% CI, 1.05-1.46) and cancer mortality (hazard ratio, 1.20; 95% CI, 1.01-1.43).
CONCLUSIONS AND RELEVANCE:
Normal-weight central obesity in women was associated with excess risk of mortality, similar to that of women with BMI-defined obesity with central obesity. These findings underscore the need for future public health guidelines to include the prevention and control of central obesity, even in individuals with normal BMI.

The Relationship between Vitamin C and Periodontal Diseases: A Systematic Review.
Tada A, Miura H.
Int J Environ Res Public Health. 2019 Jul 11;16(14). pii: E2472. doi: 10.3390/ijerph16142472. Review.
PMID: 31336735
Abstract
Vitamin C is important for preventing and slowing the progression of many diseases. There is significant evidence linking periodontal disease and vitamin C. We aimed to systematically review the studies addressing the relationship between vitamin C and periodontal disease, and the preventive ability of vitamin C against periodontal disease. Electric searches were performed using PubMed, EMBASE, Cochrane Library, and Web of Science. Studies addressing the relationships between periodontal disease and vitamin C in adults aged over 18 years were included. Quality assessment was done using the Critical Appraisal Skills Program guideline and GRADE-CERQual. There were 716 articles that were retrieved and 14 articles (seven cross-sectional studies, two case-control studies, two cohort studies, and three randomized controlled trials (RCT)) were selected after reviewing all of the articles. The vitamin C intake and blood levels were negatively related to periodontal disease in all seven cross-sectional studies. The subjects who suffer from periodontitis presented a lower vitamin C intake and lower blood-vitamin C levels than the subjects without periodontal disease in the two case-control studies. The patients with a lower dietary intake or lower blood level of vitamin C showed a greater progression of periodontal disease than the controls. The intervention using vitamin C administration improved gingival bleeding in gingivitis, but not in periodontitis. Alveolar bone absorption was also not improved. The present systematic review suggested that vitamin C contributes to a reduced risk of periodontal disease.
KEYWORDS:
Vitamin C; ascorbic acid; gingivitis; periodontal disease; periodontitis

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Association of dietary fiber intake with hyperuricemia in U.S. adults.
Sun Y, Sun J, Zhang P, Zhong F, Cai J, Ma A.
Food Funct. 2019 Jul 25. doi: 10.1039/c8fo01917g. [Epub ahead of print]
PMID: 31342970
Abstract
Current evidence on the relationship between dietary fiber intake and risk of hyperuricemia is limited. The aim of the present study was to examine their associations in the U.S. general adult population. Data from the National Health and Nutrition Examination Survey (NHANES) 2009 to 2014 were used. Dietary fiber intake was extracted through two 24 h dietary recall interviews. Hyperuricemia was defined by cut-off values of 7.0 mg dL-1 for men and 6.0 mg dL-1 for women. Multivariable logistic regression models and restricted cubic spline models were applied to explore the associations between dietary intakes of total, cereal, fruit and vegetable fiber and the risk of hyperuricemia. A total of 12 869 participants aged 20 years or older were included in the present study. The multivariable odds ratio (OR) and 95% confidence interval (CI) of hyperuricemia for the highest vs. lowest quartile intake of total fiber were 0.58 (0.46-0.74), 0.61 (0.52-0.74) for cereal fiber, 0.94 (0.76-1.16) for fruit fiber and 0.95 (0.76-1.18) for vegetable fiber. The inverse associations between dietary intakes of total fiber and cereal fiber and the risk of hyperuricemia were observed in men. In stratified analysis by age (<45 years, ≥45 years), the inverse association between total fiber intake and the risk of hyperuricemia was consistent, while cereal fiber intake was only inversely associated with hyperuricemia among participants <45 years old. Dose-response analyses showed that the risk of hyperuricemia was associated with dietary intake of total fiber in a nonlinear manner, whereas the relationship was linear for cereal fiber intake. In conclusion, dietary intakes of total fiber and cereal fiber were inversely associated with the risk of hyperuricemia in the U.S. adult population.

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The metabolomic signature of extreme longevity: naked mole rats versus mice.
Viltard M, Durand S, Pérez-Lanzón M, Aprahamian F, Lefevre D, Leroy C, Madeo F, Kroemer G, Friedlander G.
Aging (Albany NY). 2019 Jul 24. doi: 10.18632/aging.102116. [Epub ahead of print]
PMID: 31346149
https://s3-us-west-1.amazonaws.com/paperchase-aging/pdf/t75osaahJ8agHpMtC.pdf
Abstract
The naked mole-rat (Heterocephalus glaber) is characterized by a more than tenfold higher life expectancy compared to another rodent species of the same size, namely, the laboratory mouse (Mus musculus). We used mass spectrometric metabolomics to analyze circulating plasma metabolites in both species at different ages. Interspecies differences were much more pronounced than age-associated alterations in the metabolome. Such interspecies divergences affected multiple metabolic pathways involving amino, bile and fatty acids as well as monosaccharides and nucleotides. The most intriguing metabolites were those that had previously been linked to pro-health and antiaging effects in mice and that were significantly increased in the long-lived rodent compared to its short-lived counterpart. This pattern applies to α-tocopherol (also known as vitamin E) and polyamines (in particular cadaverine, N8-acetylspermidine and N1,N8-diacetylspermidine), all of which were more abundant in naked mole-rats than in mice. Moreover, the age-associated decline in spermidine and N1-acetylspermidine levels observed in mice did not occur, or is even reversed (in the case of N1-acetylspermidine) in naked mole-rats. In short, the present metabolomics analysis provides a series of testable hypotheses to explain the exceptional longevity of naked mole-rats.
KEYWORDS:
antioxidants; autophagy; catabolism; meta-organism; microbiota; spermidine

The relationship between all-cause mortality sarcopenia and sarcopenic obesity among hospitalized older people.
Atmis V, Yalcin A, Silay K, Ulutas S, Bahsi R, Turgut T, Mut Sürmeli D, Selvi Öztorun H, Yaman S, Çoşarderelioğlu Ç, Aras S, Varli M.
Aging Clin Exp Res. 2019 Jul 26. doi: 10.1007/s40520-019-01277-5. [Epub ahead of print]
PMID: 31350700
Abstract
BACKGROUND AND AIM:
Sarcopenia and sarcopenic obesity (SO) are associated with adverse health outcomes in older people. Data on sarcopenia- and SO-related mortality are insufficient for hospitalized older people. The aim of this study was to evaluate the relationship between sarcopenia, SO and mortality among hospitalized older people.
METHODS:
Two-centered prospective observational study was conducted among 350 hospitalized older people in geriatric units of two university hospitals. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People. Obesity was defined according to fat mass percentage. Medical history, cognitive status, nutritional status and functionality and laboratory tests were assessed. All-cause mortality rate was recorded at 2 years.
RESULTS:
The prevalence of SO was 21.1%. The prevalence of sarcopenia was 11.4%. Both sarcopenia (log rank p < 0.001) and SO (log rank p < 0.001) were associated with all-cause mortality at 2 years. There was no difference between sarcopenia and SO for mortality. SO (HR 5.23, p < 0.001), sarcopenia (HR 9.26, p < 0.001), male gender (HR 2.25, p = 0.035), Lawton IADL (HR 0.77, p = 0.02), heart failure (HR 3.25, p = 0.02) and chronic obstructive lung disease (HR 5.16, p = 0.01) were independently related to all-cause mortality.
DISCUSSION AND CONCLUSIONS:
Both sarcopenia and SO showed an independent relationship for 2-year all-cause mortality after hospital discharge. These results suggest that preventive and treatment options should be taken to decrease mortality associated with these conditions among hospitalized older people.
KEYWORDS:
Mortality; Obesity; Older people; Sarcopenia

Quality of dietary fat and genetic risk of type 2 diabetes: individual participant data meta-analysis.
Merino J; CHARGE Consortium Nutrition Working Group.
BMJ. 2019 Jul 25;366:l4292. doi: 10.1136/bmj.l4292.
PMID: 31345923
https://www.bmj.com/content/bmj/366/bmj.l4292.full.pdf
Abstract
OBJECTIVE:
To investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes.
DESIGN:
Individual participant data meta-analysis.
DATA SOURCES:
Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and February 2017 through electronic searches in major medical databases (Medline, Embase, and Scopus) and discussion with investigators.
REVIEW METHODS:
Data from cohort studies or multicohort consortia with available genome-wide genetic data and information about the quality of dietary fat and the incidence of type 2 diabetes in participants of European descent was sought. Prospective cohorts that had accrued five or more years of follow-up were included. The type 2 diabetes genetic risk profile was characterized by a 68-variant polygenic risk score weighted by published effect sizes. Diet was recorded by using validated cohort-specific dietary assessment tools. Outcome measures were summary adjusted hazard ratios of incident type 2 diabetes for polygenic risk score, isocaloric replacement of carbohydrate (refined starch and sugars) with types of fat, and the interaction of types of fat with polygenic risk score.
RESULTS:
Of 102 305 participants from 15 prospective cohort studies, 20 015 type 2 diabetes cases were documented after a median follow-up of 12 years (interquartile range 9.4-14.2). The hazard ratio of type 2 diabetes per increment of 10 risk alleles in the polygenic risk score was 1.64 (95% confidence interval 1.54 to 1.75, I2=7.1%, τ2=0.003). The increase of polyunsaturated fat and total omega 6 polyunsaturated fat intake in place of carbohydrate was associated with a lower risk of type 2 diabetes, with hazard ratios of 0.90 (0.82 to 0.98, I2=18.0%, τ2=0.006; per 5% of energy) and 0.99 (0.97 to 1.00, I2=58.8%, τ2=0.001; per increment of 1 g/d), respectively. Increasing monounsaturated fat in place of carbohydrate was associated with a higher risk of type 2 diabetes (hazard ratio 1.10, 95% confidence interval 1.01 to 1.19, I2=25.9%, τ2=0.006; per 5% of energy). Evidence of small study effects was detected for the overall association of polyunsaturated fat with the risk of type 2 diabetes, but not for the omega 6 polyunsaturated fat and monounsaturated fat associations. Significant interactions between dietary fat and polygenic risk score on the risk of type 2 diabetes (P>0.05 for interaction) were not observed.
CONCLUSIONS:
These data indicate that genetic burden and the quality of dietary fat are each associated with the incidence of type 2 diabetes. The findings do not support tailoring recommendations on the quality of dietary fat to individual type 2 diabetes genetic risk profiles for the primary prevention of type 2 diabetes, and suggest that dietary fat is associated with the risk of type 2 diabetes across the spectrum of type 2 diabetes genetic risk.

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Canned food intake and urinary bisphenol a concentrations: a randomized crossover intervention study.
Peng CY, Tsai EM, Kao TH, Lai TC, Liang SS, Chiu CC, Wang TN.
Environ Sci Pollut Res Int. 2019 Jul 27. doi: 10.1007/s11356-019-05534-y. [Epub ahead of print]
PMID: 31352597
Abstract
Bisphenol A (BPA) is an endocrine disruptor. To evaluate the effect of canned food consumption on internal BPA dose, urinary BPA concentrations were measured before and after intake of canned foods. This study applied a randomized crossover design, recruited 20 healthy volunteers, and divided them into two groups. One group consumed canned food; the other group consumed fresh food. After a 1-day washout, the dietary interventions were reversed. In each period, urine samples were collected immediately before meals and then 2 h, 4 h, and 6 h after meals. A mixed-effects model was used to assess BPA changes over time. Our results showed urinary BPA concentrations increased after consumption of canned food. Specifically, urinary BPA concentrations significantly differed between consumption of canned food and fresh food at 2 h, 4 h, and 6 h after intake (p values of 0.001, < 0.001, and < 0.001, respectively). Mean BPA concentrations at 2 h, 4 h, and 6 h after meals were 152%, 206%, and 79% higher, respectively, than mean BPA concentrations before meals. Urine concentration profiles of canned food intake showed that peaks were at 4 h, the increase diminished at 6 h, and returned to baseline levels at 24 h after intake. Therefore, dietary intervention and a 1-day washout period are effective for limiting internal BPA burden. This study provides convincing evidence of a human exposure route to BPA and a basis for designing interventions to mitigate exposure.
KEYWORDS:
Bisphenol A; Canned foods; Crossover study; Exposure route; Intervention

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Lifespan extension drug interventions affect adipose tissue inflammation in aging.
Mau T, O'Brien M, Ghosh AK, Miller RA, Yung R.
J Gerontol A Biol Sci Med Sci. 2019 Jul 29. pii: glz177. doi: 10.1093/gerona/glz177. [Epub ahead of print]
PMID: 31353414
Abstract
The National Institute on Aging (NIA)-sponsored Interventions Testing Program (ITP) has identified a number of dietary drug interventions that significantly extend lifespan, including rapamycin, acarbose, and 17-α estradiol. However, these drugs have diverse downstream targets, and their effects on age-associated organ-specific changes are unclear (1). Potential mechanisms by which these drugs extend life could be through their effect on inflammatory processes often noted in tissues of aging mice and humans. Our study focuses on the effects of three drugs in the ITP on inflammation in gonadal white adipose tissue (gWAT) of HET3 mice-including adiposity, adipose tissue macrophage (ATM) M1/M2 polarization, markers of cellular senescence and endoplasmic reticulum stress. We found that rapamycin led to a 56% increase of CD45+ leukocytes in gWAT, where the majority of these are ATMs. Interestingly, rapamycin led to a 217% and 106% increase of M1 (CD45+CD64+CD206-) ATMs in females and males, respectively. Our data suggest rapamycin may achieve lifespan extension in part through adipose tissue inflammation. Additionally, HET3 mice exhibit a spectrum of age-associated changes in the gWAT, but acarbose and 17-α estradiol do not strongly alter these phenotypes-suggesting that acarbose and 17- α estradiol may not influence lifespan through mechanisms involving adipose tissue inflammation.
KEYWORDS:
ITP; adipose tissue; aging; lifespan; macrophage

A Hazelnut-Enriched Diet Modulates Oxidative Stress and Inflammation Gene Expression without Weight Gain.
Di Renzo L, Cioccoloni G, Bernardini S, Abenavoli L, Aiello V, Marchetti M, Cammarano A, Alipourfard I, Ceravolo I, Gratteri S.
Oxid Med Cell Longev. 2019 Jul 4;2019:4683723. doi: 10.1155/2019/4683723. eCollection 2019.
PMID: 31354906
Abstract
INTRODUCTION:
Inflammation is associated with obesity condition and plays a pivotal role in the onset and progression of many chronic diseases. Among several nutraceutical foods, hazelnuts (Corylus avellana L.) are considered an excellent anti-inflammatory and hypolipidemic food being the second richest source of monounsaturated fatty acids among nuts and because they are rich in vitamins, minerals, and phenolic compounds.
MATERIALS AND METHODS:
A prospective pilot clinical trial on 24 healthy volunteers who consumed daily, as a snack, 40 g of hazelnuts (261.99 kcal/1096.17 kJ) for six weeks was conducted. Anthropometric measurements, body composition analysis, and nutrigenomic analysis on 12 anti-inflammatory and antioxidant genes were evaluated at baseline (T0) and after hazelnut intervention (T1).
RESULTS:
No significant changes were detected on body composition analysis after hazelnut consumption. Conversely, significant upregulation was detected for SOD1 (2-ΔΔCt = 2.42), CAT (2-ΔΔCt = 2.41), MIF (2-ΔΔCt = 4.12), PPARγ (2-ΔΔCt = 5.89), VDR (2-ΔΔCt = 3.61), MTHFR (2-ΔΔCt = 2.40), and ACE (2-ΔΔCt = 2.16) at the end of the study.
CONCLUSIONS:
According to emerging evidences, hazelnut consumption does not lead to weight gain probably due to the improvement of the body's antioxidant capacity by the upregulation of genes implied in oxidant reactions and inflammation.

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Preventable Cancer Burden Associated With Poor Diet in the United States.
Zhang FF, Cudhea F, Shan Z, Michaud DS, Imamura F, Eom H, Ruan M, Rehm CD, Liu J, Du M, Kim D, Lizewski L, Wilde P, Mozaffarian D.
JNCI Cancer Spectr. 2019 May 22;3(2):pkz034. doi: 10.1093/jncics/pkz034. eCollection 2019 Jun.
PMID: 31360907
Abstract
BACKGROUND:
Diet is an important risk factor for cancer that is amenable to intervention. Estimating the cancer burden associated with diet informs evidence-based priorities for nutrition policies to reduce cancer burden in the United States.
METHODS:
Using a comparative risk assessment model that incorporated nationally representative data on dietary intake, national cancer incidence, and estimated associations of diet with cancer risk from meta-analyses of prospective cohort studies, we estimated the annual number and proportion of new cancer cases attributable to suboptimal intakes of seven dietary factors among US adults ages 20 years or older, and by population subgroups.
RESULTS:
An estimated 80 110 (95% uncertainty interval [UI] = 76 316 to 83 657) new cancer cases were attributable to suboptimal diet, accounting for 5.2% (95% UI = 5.0% to 5.5%) of all new cancer cases in 2015. Of these, 67 488 (95% UI = 63 583 to 70 978) and 4.4% (95% UI = 4.2% to 4.6%) were attributable to direct associations and 12 589 (95% UI = 12 156 to 13 038) and 0.82% (95% UI = 0.79% to 0.85%) to obesity-mediated associations. By cancer type, colorectal cancer had the highest number and proportion of diet-related cases (n = 52 225, 38.3%). By diet, low consumption of whole grains (n = 27 763, 1.8%) and dairy products (n = 17 692, 1.2%) and high intake of processed meats (n = 14 524, 1.0%) contributed to the highest burden. Men, middle-aged (45-64 years) and racial/ethnic minorities (non-Hispanic blacks, Hispanics, and others) had the highest proportion of diet-associated cancer burden than other age, sex, and race/ethnicity groups.
CONCLUSIONS:
More than 80 000 new cancer cases are estimated to be associated with suboptimal diet among US adults in 2015, with middle-aged men and racial/ethnic minorities experiencing the largest proportion of diet-associated cancer burden in the United States.

Associations of dietary choline intake with risk of incident dementia and with cognitive performance: the Kuopio Ischaemic Heart Disease Risk Factor Study.
Ylilauri MPT, Voutilainen S, Lönnroos E, Virtanen HEK, Tuomainen TP, Salonen JT, Virtanen JK.
Am J Clin Nutr. 2019 Jul 30. pii: nqz148. doi: 10.1093/ajcn/nqz148. [Epub ahead of print]
PMID: 31360988
Abstract
BACKGROUND:
Moderate egg intake has been associated with better cognitive performance in observational studies. This association may be due to the rich content of choline, especially phosphatidylcholine, in eggs because choline has been suggested to have a role in the prevention of cognitive decline.
OBJECTIVES:
We investigated the associations of dietary choline intake with the risk of incident dementia and with cognitive performance in middle-aged and older men in the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study.
METHODS:
A population-based sample of 2497 dementia-free men aged 42-60 y was examined in 1984-1989. A subset of 482 men completed 5 different cognitive performance tests 4 y later. Dementia and Alzheimer disease diagnoses were retrieved from Finnish health registers. Dietary intakes were assessed with the use of 4-d food records at baseline. Cox regression and ANCOVA were used for the analyses. All analyses were also stratified by the apolipoprotein E phenotype (APOE-ε4 compared with other phenotypes). These data were available for 1259 men.
RESULTS:
The mean ± SD total choline intake was 431 ± 88 mg/d, of which 188 ± 63 mg/d was phosphatidylcholine. During a 21.9-y follow-up, 337 men were diagnosed with dementia. Those in the highest compared with the lowest phosphatidylcholine intake quartile had 28% (95% CI: 1%, 48%; P-trend = 0.02 across quartiles) lower multivariable-adjusted risk of incident dementia. Total choline intake had no association with the risk of incident dementia. However, both total choline and phosphatidylcholine intakes were associated with better performance in cognitive tests assessing frontal and temporal lobe functioning. For example, higher intakes were associated with better performance in verbal fluency and memory functions. The APOE phenotype had little or no impact on the associations.
CONCLUSION:
Higher phosphatidylcholine intake was associated with lower risk of incident dementia and better cognitive performance in men in eastern Finland. This trial was registered at clinicaltrials.gov as NCT03221127.
KEYWORDS:
Alzheimer disease; apolipoprotein E4; choline; cognitive function; cognitive performance; dementia; eggs; men; phosphatidylcholine; population study

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Scientists Just Released a New Playbook for Engineering Longer, Healthier Lives
By Shelly Fan - Jul 30, 2019
https://singularityhub.com/2019/07/30/scientists-just-released-a-new-playbook-for-engineering-longer-healthier-lives/
>>>>>>>>>>>
From discoveries in ageing research to therapeutics for healthy ageing
Judith Campisi, Pankaj Kapahi, Gordon J. Lithgow, Simon Melov, John C. Newman & Eric Verdin 
Naturevolume 571, pages183–192 (2019)
https://www.nature.com/articles/s41586-019-1365-2
Abstract
For several decades, understanding ageing and the processes that limit lifespan have challenged biologists. Thirty years ago, the biology of ageing gained unprecedented scientific credibility through the identification of gene variants that extend the lifespan of multicellular model organisms. Here we summarize the milestones that mark this scientific triumph, discuss different ageing pathways and processes, and suggest that ageing research is entering a new era that has unique medical, commercial and societal implications. We argue that this era marks an inflection point, not only in ageing research but also for all biological research that affects the human healthspan.

Low Protein Diets with Fixed Carbohydrate Content Promote Hyperphagia and Sympathetically Mediated Increase in Energy Expenditure.
Zapata RC, Singh A, Pezeshki A, Avirineni BS, Patra S, Chelikani PK.
Mol Nutr Food Res. 2019 Jul 31:e1900088. doi: 10.1002/mnfr.201900088. [Epub ahead of print]
PMID: 31365786
Abstract
SCOPE:
Dietary protein restriction elicits hyperphagia and increases energy expenditure; however, less is known of whether these responses are a consequence of increasing carbohydrate content. We determined the effects of protein diluted diets with fixed carbohydrate content on energy balance, hormones, and key markers of protein sensing and thermogenesis in tissues.
METHODS AND RESULTS:
Obesity-prone rats (n = 13-16/group) were randomized to diets containing fixed carbohydrate (52% calories) and varying protein concentrations: 15% (control), 10% (mild protein restriction), 5% (moderate protein restriction) or 1% (severe protein restriction) protein calories, or protein-matched to 5% protein, for 21 days. Propranolol and ondansetron were administered to interrogate the roles of sympathetic and serotonergic systems, respectively, in diet-induced changes in energy expenditure. We found that mild to moderate protein restriction promoted transient hyperphagia, whereas severe protein restriction induced hypophagia, with alterations in meal patterns. Protein restriction enhanced energy expenditure that was partly attenuated by propranolol, but not ondansetron. Moderate to severe protein restriction decreased gains in body weight, lean and fat mass, decreased postprandial glucose and leptin, but increased fibroblast growth factor-21 concentrations. Protein-matching retained lean mass suggesting that intake of dietary protein, but not calories, was important for preserving lean mass. Notably, protein restriction increased the protein and/or transcript abundance of key amino acid sensing molecules in liver and intestine (PERK, eIF2α, ATF2, CHOP, 4EBP1, FGF21), and upregulated thermogenic markers (β2AR, Klotho, HADH, UCP-1) in brown adipose tissue.
CONCLUSION:
Low protein diets promoted hyperphagia and sympathetically mediated increase in energy expenditure, prevented gains in tissue reserves, and concurrently upregulated hepatic and intestinal amino acid sensing intermediaries and thermogenic markers in brown adipose tissue. This article is protected by copyright. All rights reserved.
KEYWORDS:
energy balance; hormones; protein restriction; sympathetic signaling

Fruit and vegetable intake and liver cancer risk: a meta-analysis of prospective cohort studies.
Guo XF, Shao XF, Li JM, Li S, Li KL, Li D.
Food Funct. 2019 Jul 31. doi: 10.1039/c9fo00804g. [Epub ahead of print] Review.
PMID: 31364650
https://sci-hub.tw/10.1039/c9fo00804g
Abstract
The associations of vegetable and fruit intake with liver cancer risk have been inconsistent based on epidemiological studies. The present study aimed to quantitatively evaluate these associations with prospective cohort studies. A systematic literature search was performed with PubMed and Scopus databases up to June 2019. Multivariate-adjusted relative risks (RRs) with a corresponding 95% confidence interval (CI) for the highest versus lowest category were pooled by using a random-effects model. Pre-specified subgroup and univariate meta-regression analyses were performed to identify the sources of heterogeneity. Dose-response analysis was conducted by using the variance weighted least squares regression model. Nine independent prospective cohort studies with 1703 liver cancer events and 1 326 176 participants were included for data synthesis. The summary estimates showed that higher vegetable intake was associated with a 39% (95%CI: 0.50, 0.75) reduction in liver cancer risk, with no significant between-study heterogeneity (P = 0.057). Dose-response analysis indicated that the risk of liver cancer was reduced by 4% (95%CI: 0.97, 0.95; P for trend <0.001) with a 100 gram per day increment of vegetable intake. Subgroup analysis showed that higher intakes of vegetables were associated with a 50% (95%CI: 0.35, 0.72) reduction of liver cancer risk in males, but not in females. However, a non-significant association was found between fruit intake and liver cancer risk. The present study provides strong evidence that higher intakes of vegetables would have beneficial effects on the prevention of liver cancer, especially for males.

Metabolic phenotypes of obese, overweight, and normal weight individuals and risk of chronic kidney disease: a systematic review and meta-analysis.
Alizadeh S, Esmaeili H, Alizadeh M, Daneshzad E, Sharifi L, Radfar H, Radaei MK.
Arch Endocrinol Metab. 2019 Jul 29. pii: S2359-39972019005006103. doi: 10.20945/2359-3997000000149. [Epub ahead of print]
PMID: 31365625
Abstract
OBJECTIVE:
Chronic kidney disease (CKD) risk is inconsistent in the normal-weight, overweight, and obese individuals due to the heterogeneity of metabolic status. This meta-analysis aimed to examine the combined effects of body mass index (BMI) and metabolic status on CKD risk.
MATERIALS AND METHODS:
The MEDLINE, EMBASE, and Web of Knowledge databases were systematically searched up to March 2019 to identify all eligible studies investigating the CKD risk (defined as GFR < 60 mL/min per 1.73 m2 and/or microalbuminuria or proteinuria) associated with the body size phenotypes which are known as metabolically unhealthy normal-weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight, metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO). The classification of subjects in included studies as metabolically unhealthy was based on the presence of three components of metabolic syndrome. BMI categorization was based on the criteria of included studies. The risk estimates and 95% confidence intervals (CIs) were extracted and pooled using random effects analysis.
RESULTS:
A total of 9 prospective cohort studies with 128773 participants and 4797 incident cases were included in the meta-analysis. Compared with healthy normal-weight individuals as reference, MUNW and MHO subjects showed an increased risk for CKD events with a pooled RR of 1.58 (95% CI = 1.28-1.96) in MUNW and 1.55 (95% CI = 1.34-1.79) in MHO persons. Also, MHOW was at increased risk for CKD (RR = 1.34, 95% CI = 1.20-1.51). MUHO individuals were at the highest risk for the development of CKD (RR = 2.13, 95% CI = 1.66-2.72).
CONCLUSIONS:
Individuals with metabolic abnormality, although at normal-weight, have an increased risk for CKD. Healthy overweight and obese individuals had higher risk; refuting the notion that metabolically healthy overweight and obese phenotypes are benign conditions.

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Hypothalamic leptin sensitivity and health benefits of time-restricted feeding are dependent on the time of day in male mice.
Boucsein A, Rizwan MZ, Tups A.
FASEB J. 2019 Jul 31:fj201901004R. doi: 10.1096/fj.201901004R. [Epub ahead of print]
PMID: 31366239
Abstract
Synchronization between biologic clocks and metabolism is crucial for most species. Here, we examined the ability of leptin, important in the control of energy metabolism, to induce leptin signaling at the molecular as well as the behavioral level throughout the 24-h day in mice fed either a control or a high-fat diet (HFD). Furthermore, we investigated the effects of time-restricted feeding (TRF; a limitation of HFD access to 6 h each day) on energy metabolism during different periods throughout the 24-h day. In control mice, molecular leptin sensitivity was highest at zeitgeber time (ZT)0 (lights on), declining during the light phase, and increasing during the dark phase. Surprisingly, leptin resistance in HFD-fed mice was only present from the middle of the dark to the middle of the light period. Specifically, when TRF occurred from ZT21 to ZT3 (when leptin resistance in HFD-fed mice was most profound), it resulted in a disruption of the daily rhythms of locomotor activity and energy expenditure and in increased plasma insulin levels compared with other TRF periods. These data provide evidence that leptin sensitivity is controlled by the circadian rhythm and that TRF periods may be most efficient when aligned with the leptin-sensitive period.
KEYWORDS:
biological clock; daily rhythm; diet; energy metabolism; periodic fasting

Circulating Selenium and Cardiovascular or All-Cause Mortality in the General Population: a Meta-Analysis.
Xiang S, Dai Z, Man C, Fan Y.
Biol Trace Elem Res. 2019 Jul 31. doi: 10.1007/s12011-019-01847-8. [Epub ahead of print] Review.
PMID: 31368032
Abstract
The association of circulating selenium level with mortality remains controversial. This meta-analysis investigated the association between elevated circulating selenium level and cardiovascular or all-cause mortality in the general population. PubMed and Embase databases (up to January 20, 2019) were searched for observational studies or post hoc analyses of randomized controlled trials that evaluated the association between elevated circulating selenium level and cardiovascular or all-cause mortality in the general population. Twelve observational studies (ten cohort and two case-control studies) with a total of 25,667 individuals were included. Comparison with the lowest and the highest circulating selenium level showed that the pooled risk ratio (RR) values of all-cause mortality and cardiovascular mortality were 1.36 (95% confidence intervals [CI] 1.18-1.58) and 1.35 (95% CI 1.13-1.62), respectively. When analyzed selenium level as a continuous variable, each standard deviation selenium increase significantly reduced 20% all-cause mortality risk. However, the lowest circulating selenium level was not associated with a high risk of coronary mortality (RR 1.43; 95% CI 0.93-2.19). This meta-analysis indicated that low circulating selenium level was associated with higher risk of cardiovascular or all-cause mortality in the general population. Low circulating selenium level did not confer significant effect on coronary death.
KEYWORDS:
All-cause mortality; Cardiovascular mortality; Coronary death; Meta-analysis; Selenium

Sex differences in the association of risk factors for heart failure incidence and mortality.
Sillars A, Ho FK, Pell GP, Gill JMR, Sattar N, Gray S, Celis-Morales C.
Heart. 2019 Jul 31. pii: heartjnl-2019-314878. doi: 10.1136/heartjnl-2019-314878. [Epub ahead of print]
PMID: 31366573
Abstract
BACKGROUND:
There are known risk factors associated with the development of heart failure (HF), but it is not fully understood whether these differ by sex.
OBJECTIVES:
To investigate sex differences in risk factors for HF incidence and mortality.
METHODS:
468 941 participants (55.9% women, age range 37-73 years) were included. Established CVD risk factors (hypertension, hypercholesterolaemia, diabetes type 1 and 2, adiposity, smoking, physical activity and poor diet) and novel risk factors (grip strength, fitness, TV viewing and sleep duration) were the exposures of interest. HF incidence and mortality were the outcomes.
RESULTS:
Over a mean follow-up of 9.0 years, 1812 participants developed HF and 763 died due to HF. Women with type 1 diabetes (T1DM), type 2 diabetes (T2DM), hypertension, hypercholesterolaemia, low levels of physical activity and fitness, low strength, high levels of TV viewing, sleep duration <7 hours/day, smokers; those who were underweight and who were obese, had high body surface area and those who drink >14 units of alcohol were at higher risk of HF incidence. However, in women T2DM, hypercholesterolaemia, >3 hours/day of TV and sleep <7 hours/day, low level of physical activity and high level of TV viewing were more strongly associated with HF incidence compared with men.
CONCLUSION:
Several modifiable risk factors (in particular diabetes) appear more strongly associated with HF in women compared with men. The relevance of these findings to HF characteristics and future outcomes needs to be established.
KEYWORDS:
epidemiology; heart failure; obesity

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Global Incidence of Frailty and Prefrailty Among Community-Dwelling Older Adults: A Systematic Review and Meta-analysis.
Ofori-Asenso R, Chin KL, Mazidi M, Zomer E, Ilomaki J, Zullo AR, Gasevic D, Ademi Z, Korhonen MJ, LoGiudice D, Bell JS, Liew D.
JAMA Netw Open. 2019 Aug 2;2(8):e198398. doi: 10.1001/jamanetworkopen.2019.8398.
PMID: 31373653
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2740784
Abstract
IMPORTANCE:
Frailty is a common geriatric syndrome of significant public health importance, yet there is limited understanding of the risk of frailty development at a population level.
OBJECTIVE:
To estimate the global incidence of frailty and prefrailty among community-dwelling adults 60 years or older.
DATA SOURCES:
MEDLINE, Embase, PsycINFO, Web of Science, CINAHL Plus, and AMED (Allied and Complementary Medicine Database) were searched from inception to January 2019 without language restrictions using combinations of the keywords frailty, older adults, and incidence. The reference lists of eligible studies were hand searched.
STUDY SELECTION:
In the systematic review, 2 authors undertook the search, article screening, and study selection. Cohort studies that reported or had sufficient data to compute incidence of frailty or prefrailty among community-dwelling adults 60 years or older at baseline were eligible.
DATA EXTRACTION AND SYNTHESIS:
The methodological quality of included studies was assessed using The Joanna Briggs Institute's Critical Appraisal Checklist for Prevalence and Incidence Studies. Meta-analysis was conducted using a random-effects (DerSimonian and Laird) model.
MAIN OUTCOMES AND MEASURES:
Incidence of frailty (defined as new cases of frailty among robust or prefrail individuals) and incidence of prefrailty (defined as new cases of prefrailty among robust individuals), both over a specified duration.
RESULTS:
Of 15 176 retrieved references, 46 observational studies involving 120 805 nonfrail (robust or prefrail) participants from 28 countries were included in this systematic review. Among the nonfrail individuals who survived a median follow-up of 3.0 (range, 1.0-11.7) years, 13.6% (13 678 of 100 313) became frail, with the pooled incidence rate being 43.4 (95% CI, 37.3-50.4; I2 = 98.5%) cases per 1000 person-years. The incidence of frailty was significantly higher in prefrail individuals than robust individuals (pooled incidence rates, 62.7 [95% CI, 49.2-79.8; I2 = 97.8%] vs 12.0 [95% CI, 8.2-17.5; I2 = 94.9%] cases per 1000 person-years, respectively; P for difference < .001). Among robust individuals in 21 studies who survived a median follow-up of 2.5 (range, 1.0-10.0) years, 30.9% (9974 of 32 268) became prefrail, with the pooled incidence rate being 150.6 (95% CI, 123.3-184.1; I2 = 98.9%) cases per 1000 person-years. The frailty and prefrailty incidence rates were significantly higher in women than men (frailty: 44.8 [95% CI, 36.7-61.3; I2 = 97.9%] vs 24.3 [95% CI, 19.6-30.1; I2 = 8.94%] cases per 1000 person-years; prefrailty: 173.2 [95% CI, 87.9-341.2; I2 = 99.1%] vs 129.0 [95% CI, 73.8-225.0; I2 = 98.5%] cases per 1000 person-years). The incidence rates varied by diagnostic criteria and country income level. The frailty and prefrailty incidence rates were significantly reduced when accounting for the risk of death.
CONCLUSIONS AND RELEVANCE:
Results of this study suggest that community-dwelling older adults are prone to developing frailty. Increased awareness of the factors that confer high risk of frailty in this population subgroup is vital to inform the design of interventions to prevent frailty and to minimize its consequences.

The effects of age and fasting models on blood pressure, insulin/glucose profile and expression of longevity proteins in male rats.
Badreh F, Joukar S, Badavi M, Rashno M, Dehesh T.
Rejuvenation Res. 2019 Aug 2. doi: 10.1089/rej.2019.2205. [Epub ahead of print]
PMID: 31373257
Abstract
Intermittent fasting can be effective in reducing metabolic disorders and age-related diseases. However, there remain questions about the effects of fasting with respect to the age in which fasting begins, the fasting models and the mechanisms involved. We investigated the effects of age of beginning fasting and chronic mild and severe fasting models on blood pressure, insulin/glucose profile and expression of klotho, SIRT1 and SIRT3 in male Wistar rats. Young (3 months), middle-aged (12 months) and old (22 months) animals were randomly divided into three subgroups and fed as ad libitum (AL), ad libitum with fasting 1 day per week (FW), and ad libitum with fasting every other day (EOD) respectively for three months. The FW reduced the weight gain in young animals (P<0.001 vs. AL), while EOD induced weight loss in all three age categories (P<0.001). Aging was associated with high blood pressure, high glucose and insulin levels. Both FW and EOD feeding decreased blood pressure and blood glucose level (P<0.001) and EOD decreased insulin level (P<0.05 vs. AL) in old animals. Parallel to aging the expression of SIRT1 and klotho significantly decreased in plasma and EOD feeding recovered this defect. Both FW and EOD feedings increased the expression of SIRT3 in middle-aged and old rats. Age is a determining factor for the effectiveness of fasting and old animals respond more desirably to fasting. The effect of EOD fasting is more effective than FW fasting in improving the metabolic factors, partly through the recovery of SIRT1 and klotho.

Cumulative intake of artificially sweetened and sugar-sweetened beverages and risk of incident type 2 diabetes in young adults: the Coronary Artery Risk Development In Young Adults (CARDIA) Study.
Hirahatake KM, Jacobs DR, Shikany JM, Jiang L, Wong ND, Steffen LM, Odegaard AO.
Am J Clin Nutr. 2019 Aug 2. pii: nqz154. doi: 10.1093/ajcn/nqz154. [Epub ahead of print]
PMID: 31374564
Abstract
BACKGROUND:
Epidemiological evidence has demonstrated a positive association between artificially sweetened beverage (ASB) and sugar-sweetened beverage (SSB) consumption and type 2 diabetes (T2D) risk. However, research informing this topic in young adults is limited.
OBJECTIVE:
This study examined the association between ASB, SSB, and total sweetened beverage (TSB; combined ASB and SSB) consumption and T2D risk in young adults.
METHODS:
A prospective analysis of 4719 Black and White men and women aged 18-30 y at baseline was conducted from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Each participant's beverage intake was assessed using the CARDIA Diet History at baseline and at study Years 7 and 20. Multivariable Cox proportional hazards regression models were used to examine cumulative average ASB, SSB, and TSB intakes and risk of T2D.
RESULTS:
During the 30-y follow-up period, 680 participants developed T2D. ASB consumption was associated with a 12% greater risk of T2D per serving/day (HR 1.12, 95% CI 1.04-1.20) in a model adjusted for lifestyle factors, diet quality, and dieting behavior. Further adjustments for baseline BMI (HR 1.07, 95% CI 0.99-1.14) and weight change during follow-up (HR 1.04, 95% CI 0.97-1.12) attenuated the association. SSB and TSB consumption as continuous variables per 1 serving/day of intake were associated with 6% and 5% increased risks of T2D, respectively (HRSSB 1.06, 95% CI 1.01-1.10; HRTSB 1.05, 95% CI 1.01-1.09), in the model accounting for lifestyle factors, dieting behavior, baseline BMI, and weight change. Results were consistent when the exposures were modeled in categories of consumption and quintiles.
CONCLUSIONS:
In young adults, long-term ASB, SSB, and TSB consumption were associated with increased risks of T2D. However, the estimates for ASB were attenuated when accounting for weight changes.
EYWORDS:
CARDIA; Coronary Artery Risk Development in Young Adults; artificially sweetened beverage; diabetes; diet; sugar-sweetened beverage

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A Randomised Controlled Trial on the Effectiveness and Adherence of Modified Alternate-day Calorie Restriction in Improving Activity of Non-Alcoholic Fatty Liver Disease.
Johari MI, Yusoff K, Haron J, Nadarajan C, Ibrahim KN, Wong MS, Hafidz MIA, Chua BE, Hamid N, Arifin WN, Ma ZF, Lee YY.
Sci Rep. 2019 Aug 2;9(1):11232. doi: 10.1038/s41598-019-47763-8.
PMID: 31375753
https://www.nature.com/articles/s41598-019-47763-8.pdf
Abstract
Currently, there is no effective therapy for non-alcoholic fatty liver disease (NAFLD), although intensive calorie restriction is typically recommended but dietary adherence is an issue. The current study aimed to determine the effectiveness and adherence of eight weeks of modified alternate-day calorie restriction (MACR) in the control of NAFLD activity. This was a randomized controlled trial with MACR as the intervention and normal habitual diet as control. The outcome measures were body mass index (BMI), blood lipids, fasting blood sugar (FBS), liver enzymes (ALT and AST), and ultrasonographic measurements of liver steatosis and shear wave elastography (SWE). Per-protocol (PP) and intention-to-treat (ITT) analysis were performed within and between-groups with P < 0.05 as significant. 43 individuals with NAFLD satisfied study entry criteria, 33 were randomized to MACR and 10 to control group, and, 30 from MACR and 9 from control group completed PP. In between-group analysis of MACR vs. control, BMI were reduced in PP (P = 0.02) and ITT (P = 0.04). Only ALT was reduced in between-group analysis of MACR vs. control, both PP and ITT (P = 0.02 and 0.04 respectively). No reductions in all lipid parameters and FBS were found in between-group analyses (PP and ITT, all P > 0.22). Both liver steatosis grades and fibrosis (SWE) scores were reduced in between-group analyses of MACR vs. controls (PP and ITT, all P < 0.01). Adherence level remained between 75-83% throughout the study. As conclusion, 8 weeks of MACR protocol appears more effective than usual habitual diet in the control of NAFLD activity and with good adherence rate.

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Relevance of physical function in the association of red and processed meat intake with all-cause, cardiovascular, and cancer mortality.
Argyridou S, Zaccardi F, Davies MJ, Khunti K, Yates T.
Nutr Metab Cardiovasc Dis. 2019 Jun 27. pii: S0939-4753(19)30248-0. doi: 10.1016/j.numecd.2019.06.019. [Epub ahead of print]
PMID: 31377183
https://sci-hub.tw/10.1016/j.numecd.2019.06.019
Abstract
BACKGROUND AND AIMS:
Intake of red and processed meat has been associated with a higher risk of morbidity and mortality; it is unknown whether these associations are modified by overall physical health. This study examined the associations of red and processed meat consumption with all-cause, cardiovascular, and cancer mortality and investigated whether markers of physical function modified the associations.
METHODS AND RESULTS:
This observational cohort study used UK Biobank data derived from 419,075 participants free from cancer and cardiovascular disease. Cox models assessed the association of red and processed meat consumption (obtained from a baseline food frequency questionnaire) with mortality, adjusted for potential confounders. Objectively measured handgrip strength and self-reported walking pace were used as interaction terms. The median age was 57 (interquartile range, 49-63) years and 54.9% were women. Over 7 years of follow-up, 8586 all-cause, 1660 cardiovascular, and 4812 cancer deaths occurred. Each additional serving per week of red and processed meat was associated with a hazard ratio (HR) of 1.037 (95% CI: 1.028-1.047) for all-cause; 1.030 (1.009-1.051) for cardiovascular; and 1.029 (1.016-1.042) for cancer mortality. The association of red and processed meat consumption was modified by walking pace, with brisk walkers having the lowest risk per additional serving for all-cause and cancer mortality (HR 1.025; 1.006-1.045 and 1.015; 0.990-1.040, respectively); no interaction was observed for handgrip strength.
CONCLUSION:
The known risk of mortality associated with red and processed meat consumption may be lower in those with high physical function.
KEYWORDS:
Handgrip strength; Mortality; Processed meat; Red meat; Walking pace

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Relevance of physical function in the association of red and processed meat intake with all-cause, cardiovascular, and cancer mortality.
Argyridou S, Zaccardi F, Davies MJ, Khunti K, Yates T.
Nutr Metab Cardiovasc Dis. 2019 Jun 27. pii: S0939-4753(19)30248-0. doi: 10.1016/j.numecd.2019.06.019. [Epub ahead of print]
PMID: 31377183
https://sci-hub.tw/10.1016/j.numecd.2019.06.019
Abstract
BACKGROUND AND AIMS:
Intake of red and processed meat has been associated with a higher risk of morbidity and mortality; it is unknown whether these associations are modified by overall physical health. This study examined the associations of red and processed meat consumption with all-cause, cardiovascular, and cancer mortality and investigated whether markers of physical function modified the associations.
METHODS AND RESULTS:
This observational cohort study used UK Biobank data derived from 419,075 participants free from cancer and cardiovascular disease. Cox models assessed the association of red and processed meat consumption (obtained from a baseline food frequency questionnaire) with mortality, adjusted for potential confounders. Objectively measured handgrip strength and self-reported walking pace were used as interaction terms. The median age was 57 (interquartile range, 49-63) years and 54.9% were women. Over 7 years of follow-up, 8586 all-cause, 1660 cardiovascular, and 4812 cancer deaths occurred. Each additional serving per week of red and processed meat was associated with a hazard ratio (HR) of 1.037 (95% CI: 1.028-1.047) for all-cause; 1.030 (1.009-1.051) for cardiovascular; and 1.029 (1.016-1.042) for cancer mortality. The association of red and processed meat consumption was modified by walking pace, with brisk walkers having the lowest risk per additional serving for all-cause and cancer mortality (HR 1.025; 1.006-1.045 and 1.015; 0.990-1.040, respectively); no interaction was observed for handgrip strength.
CONCLUSION:
The known risk of mortality associated with red and processed meat consumption may be lower in those with high physical function.
KEYWORDS:
Handgrip strength; Mortality; Processed meat; Red meat; Walking pace

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Phosphatidylcholine Extends Lifespan via DAF-16 and Reduces Amyloid-Beta-Induced Toxicity in Caenorhabditis elegans.
Kim SH, Kim BK, Park S, Park SK.
Oxid Med Cell Longev. 2019 Jul 11;2019:2860642. doi: 10.1155/2019/2860642. eCollection 2019.
PMID: 31379987
Abstract
Phosphatidylcholine is one of the major phospholipids comprising cellular membrane and is known to have several health-promoting activities, including the improvement of brain function and liver repair. In this paper, we examine the in vivo effect of dietary supplementation with phosphatidylcholine on the response to environmental stressors and aging in C. elegans. Treatment with phosphatidylcholine significantly increased the survival of worms under oxidative stress conditions. However, there was no significant difference in response to stresses caused by heat shock or ultraviolet irradiation. Oxidative stress is believed to be one of the major causal factors of aging. Then, we examined the effect of phosphatidylcholine on lifespan and age-related physiological changes. Phosphatidylcholine showed a lifespan-extending effect and a reduction in fertility, possibly as a tradeoff for long lifespan. Age-related decline of motility was also significantly delayed by supplementation with phosphatidylcholine. Interestingly, the expressions of well-known longevity-assuring genes, hsp-16.2 and sod-3, were significantly upregulated by dietary intervention with phosphatidylcholine. DAF-16, a transcription factor modulating stress response genes, was accumulated in the nucleus by phosphatidylcholine treatment. Increase of the ROS level with phosphatidylcholine suggests that the antioxidant and lifespan-extending effects are due to the hormetic effect of phosphatidylcholine. Phosphatidylcholine also showed a protective effect against amyloid beta-induced toxicity in Alzheimer's disease model animals. Experiments with long-lived mutants revealed that the lifespan-extending effect of phosphatidylcholine specifically overlapped with that of reduced insulin/IGF-1-like signaling and required DAF-16. These findings showed the antioxidant and antiaging activities of phosphatidylcholine for the first time in vivo. Further studies focusing on the identification of underlying cellular mechanisms involved in the antiaging effect will increase the possibility of using phosphatidylcholine for the development of antiaging therapeutics.

Coffee Consumption and Risk of Atrial Fibrillation in the Physicians' Health Study.
Bodar V, Chen J, Gaziano JM, Albert C, Djoussé L.
J Am Heart Assoc. 2019 Aug 6;8(15):e011346. doi: 10.1161/JAHA.118.011346. Epub 2019 Aug 5.
PMID: 31378120
Abstract
Background Although coffee consumption is often reported as a trigger for atrial fibrillation (AF) among patients with paroxysmal AF, prospective studies on the relation of coffee consumption with AF risk have been inconsistent. Hence, we sought to assess the association between coffee consumption and risk of AF in men. Methods and Results We prospectively studied men who participated in the Physicians' Health Study (N=18 960). Coffee consumption was assessed through self-reported food frequency questionnaires. The incidence of AF was assessed through annual questionnaires and validated through review of medical records in a subsample. Cox proportional hazard models were used to calculate hazard ratios and 95% CIs of AF. The average age was 66.1 years. A total of 2098 new cases of AF occurred during a mean follow-up of 9 years. Hazard ratios (95% CI) of AF were 1.0 (reference), 0.85 (0.71-1.02), 1.07 (0.88-1.30), 0.93 (0.74-1.17), 0.85 (0.74-0.98), 0.86 (0.76-0.97), and 0.96 (0.80-1.14) for coffee consumption of rarely/never, ≤1 cup/week, 2 to 4 cups/week, 5 to 6 cups/week, 1 cup/day, 2 to 3 cups/day, and 4+ cups/day, respectively; adjusting for age, smoking, alcohol intake, and exercise (P for nonlinear trend=0.01). In a secondary analysis the multivariable adjusted hazard ratio (95% CI) of AF per standard deviation (149-mg) change in caffeine intake was 0.97 (0.92-1.02). Conclusions Our data suggest a lower risk of AF among men who reported coffee consumption of 1 to 3 cups/day.
KEYWORDS:
atrial fibrillation; caffeine; cardiovascular disease; coffee; epidemiology and Nutrition

Can regular long-term breakfast cereals consumption benefits lower cardiovascular diseases and diabetes risk? A longitudinal population-based study.
Xu X, Parker D, Inglis SC, Byles J.
Ann Epidemiol. 2019 Jul 11. pii: S1047-2797(19)30041-9. doi: 10.1016/j.annepidem.2019.07.004. [Epub ahead of print]
PMID: 31378560
Abstract
PURPOSE:
Studies indicate breakfast cereals may reduce the risk of overweight, cardiovascular diseases, and diabetes, but a limited number of longitudinal studies have explored these relationships, indicating the need for further assessment.
METHODS:
We used 45 and Up Study data to examine the longitudinal association between breakfast cereals (and different categories of cereals) and heart disease, stroke, and diabetes. Dietary consumption was assessed by a short food frequency questionnaire. Diagnosed heart disease, stroke, and diabetes were self-reported. Generalized estimating equation models were used to examine the longitudinal associations.
RESULTS:
Of a total of 142,503 participants (aged 45 years and older), people in the older age group (aged 80 or older) had significantly higher breakfast cereal consumption (P < .001) than those in the younger age group (aged 45-64 years). A significantly inverse association was found between breakfast muesli and heart disease, stroke, and diabetes across all age groups. Associations between other categories of breakfast cereals (biscuit, bran, and oat cereals) and these three diseases differed by age groups. A positive association was found between oat cereals and diabetes for people in the younger age groups (aged 80 years and younger), but not for people in the older age group (aged 80 years and older).
CONCLUSIONS:
The benefit of breakfast muesli consumption was highlighted in prevention of these three diseases. The result suggests that age-specific dietary guidelines, with a particular focus on the types of breakfast cereals consumption in prevention of chronic diseases for older people need to be developed.
KEYWORDS:
Breakfast cereals; Cardiovascular diseases; Diabetes risk; Longitudinal data analysis; Survey data

Impact of different types of olive oil on cardiovascular risk factors: A systematic review and network meta-analysis.
Schwingshackl L, Krause M, Schmucker C, Hoffmann G, Rücker G, Meerpohl JJ.
Nutr Metab Cardiovasc Dis. 2019 Jul 8. pii: S0939-4753(19)30266-2. doi: 10.1016/j.numecd.2019.07.001. [Epub ahead of print]
PMID: 31378629
Abstract
BACKGROUND AND AIM:
This network meta-analysis (NMA) compares the effects of different types of olive oil (OO) on cardiovascular risk factors.
METHODS AND RESULTS:
Literature search was conducted on three electronic databases (Medline, Web of Science, and Cochrane Central).
INCLUSION CRITERIA:
Randomized controlled trials (RCTs) (≥3 weeks duration of intervention) comparing at least two of the following types of OO: refined OO (ROO), mixed OO (MOO), low phenolic (extra) virgin OO (LP(E)VOO), and high phenolic (extra) virgin OO (HP(E)VOO). Random-effects NMA was performed for seven outcomes; and surface under the cumulative ranking curve (SUCRA) was estimated, using an analytical approach (P-score). Thirteen RCTs (16 reports) with 611 mainly healthy participants (mean age: 26-70 years) were identified. No differences for total cholesterol, HDL-cholesterol, triacylglycerols, and diastolic blood pressure were observed comparing ROO, MOO, LP(E)VOO and HP(E)VOO. HP(E)VOO slightly reduce LDL-cholesterol (LDL-C) compared to LP(E)VOO (mean difference [MD]: -0.14 mmol/L, 95%-CI: -0.28, -0.01). Both, HP(E)VOO and LP(E)VOO reduces SBP compared to ROO (range of MD: -2.99 to -2.87 mmHg), and HP(E)VOO may improve oxidized LDL-cholesterol (oxLDL-C) compared to ROO (standardized MD: -0.68, 95%-CI: -1.31, -0.04). In secondary analyses, EVOO may reduce oxLDL-C compared to ROO, and a dose-response relationship between higher intakes of phenolic compounds from OO and lower SBP and oxLDL-C values was detected. HP(E)VOO was ranked as best treatment for LDL-C (P-score: 0.83), oxLDL-C (0.88), and SBP (0.75).
CONCLUSIONS:
HP(E)VOO may improve some cardiovascular risk factors, however, public health implications are limited by overall low or moderate certainty of evidence.
KEYWORDS:
Cardiovascular risk factors; Extra virgin olive oil; Network meta-analysis; Olive oil; Phenolic compounds; Ranking

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A serum protein signature of APOE genotypes in centenarians.
Sebastiani P, Monti S, Morris M, Gurinovich A, Toshiko T, Andersen SL, Sweigart B, Ferrucci L, Jennings LL, Glass DJ, Perls TT.
Aging Cell. 2019 Aug 5:e13023. doi: 10.1111/acel.13023. [Epub ahead of print]
PMID: 31385390
https://onlinelibrary.wiley.com/doi/pdf/10.1111/acel.13023
Abstract
The discovery of treatments to prevent or delay dementia and Alzheimer's disease is a priority. The gene APOE is associated with cognitive change and late-onset Alzheimer's disease, and epidemiological studies have provided strong evidence that the e2 allele of APOE has a neuroprotective effect, it is associated with increased longevity and an extended healthy lifespan in centenarians. In this study, we correlated APOE genotype data of 222 participants of the New England Centenarian Study, including 75 centenarians, 82 centenarian offspring, and 65 controls, comprising 55 carriers of APOE e2 , with aptamer-based serum proteomics (SomaLogic technology) of 4,785 human proteins corresponding to 4,137 genes. We discovered a signature of 16 proteins that associated with different APOE genotypes and replicated the signature in three independent studies. We also show that the protein signature tracks with gene expression profiles in brains of late-onset Alzheimer's disease versus healthy controls. Finally, we show that seven of these proteins correlate with cognitive function patterns in longitudinally collected data. This analysis in particular suggests that Baculoviral IAP repeat containing two (BIRC2) is a novel biomarker of neuroprotection that associates with the neuroprotective allele of APOE. Therefore, targeting APOE e2 molecularly may preserve cognitive function.
KEYWORDS:
APOE; SomaLogic; centenarian; cognitive function; genotypes; protein

The Effects of Beetroot Juice on Blood Pressure, Microvascular Function and Large-Vessel Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Pilot Study in Healthy Older Adults.
Jones T, Dunn EL, Macdonald JH, Kubis HP, McMahon N, Sandoo A.
Nutrients. 2019 Aug 2;11(8). pii: E1792. doi: 10.3390/nu11081792.
PMID: 31382524
Abstract
: Dietary nitrate (NO3-) has been reported to improve endothelial function (EF) and blood pressure (BP). However, most studies only assess large-vessel EF with little research on the microvasculature. Thus, the aim of the present pilot study is to examine NO3- supplementation on microvascular and large-vessel EF and BP. Twenty older adults (63 ± 6 years) were randomized to a beetroot juice (BRJ) or placebo (PLA) group for 28 (±7) days and attended three laboratory visitations. Across visitations, blood pressure, microvascular function and large-vessel EF were assessed by laser Doppler imaging (LDI) with iontophoresis of vasoactive substances and flow-mediated dilatation (FMD), respectively. Plasma NO3-concentrations, BP and the presence of NO3- reducing bacteria were also assessed. Plasma NO3- increased following two weeks of BRJ supplementation (p = 0.04) along with a concomitant decrease in systolic and diastolic BP of approximately -6 mmHg and -4 mmHg, respectively (p = 0.04; p = 0.01, respectively). BP remained unchanged in the PLA group. There were no significant differences in endothelium-dependent or endothelium-independent microvascular responses between groups. FMD increased by 1.5% following two weeks of BRJ (p = 0.04), with only a minimal (0.1%) change for the PLA group. In conclusion, this pilot study demonstrated that medium-term BRJ ingestion potentially improves SBP, DBP and large-vessel EF in healthy older adults. The improvements observed in the present study are likely to be greater in populations presenting with endothelial dysfunction. Thus, further prospective studies are warranted in individuals at greater risk for cardiovascular disease.
KEYWORDS:
blood pressure; dietary nitrate; endothelial dysfunction; endothelial function; large-vessels; microvessels

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Association between meat consumption and risk of breast cancer: Findings from the Sister Study.
Lo JJ, Park YM, Sinha R, Sandler DP.
Int J Cancer. 2019 Aug 6. doi: 10.1002/ijc.32547. [Epub ahead of print]
PMID: 31389007
Abstract
Meat consumption has been postulated to increase the risk of breast cancer, but this association has not been consistently seen. We examined the association between consumption of different types of meat, meat mutagens and incident invasive breast cancer. Information on consumption of different meat categories and meat cooking practice behaviors was obtained from 42,012 Sister Study participants who completed a Block 1998 Food Frequency Questionnaire at enrollment (2003-2009) and satisfied eligibility criteria. Exposure to meat type and meat mutagens was calculated, and associations with invasive breast cancer risk were estimated using multivariable Cox proportional hazards regression. During follow-up (mean, 7.6 years), 1,536 invasive breast cancers were diagnosed at least 1 year after enrollment. Increasing consumption of red meat was associated with increased risk of invasive breast cancer (HRhighest vs. lowest quartile :1.23, 95% CI: 1.02-1.48, ptrend = 0.01). Conversely, increasing consumption of poultry was associated with decreased invasive breast cancer risk (HR highest vs. lowest quartile : 0.85; 95% CI: 0.72-1.00; ptrend = 0.03). In a substitution model with combined red meat and poultry consumption held constant, substituting poultry for red meat was associated with decreased invasive breast cancer risk (HR highest vs. lowest quartile of poultry consumption: 0.72, 95% CI: 0.58-0.89). No associations were observed for cooking practices, estimated heterocyclic amines or heme iron from red meat consumption with breast cancer risk. Red meat consumption may increase the risk of invasive breast cancer, whereas poultry consumption may be associated with reduced risk. Substituting poultry for red meat could reduce breast cancer risk.
KEYWORDS:
breast cancer; poultry; red meat

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Association of ideal cardiovascular health at age 50 with incidence of dementia: 25 year follow-up of Whitehall II cohort study.
Sabia S, Fayosse A, Dumurgier J, Schnitzler A, Empana JP, Ebmeier KP, Dugravot A, Kivimäki M, Singh-Manoux A.
BMJ. 2019 Aug 7;366:l4414. doi: 10.1136/bmj.l4414.
PMID: 31391187
https://www.bmj.com/content/bmj/366/bmj.l4414.full.pdf
Abstract
OBJECTIVES:
To examine the association between the Life Simple 7 cardiovascular health score at age 50 and incidence of dementia.
DESIGN:
Prospective cohort study.
SETTING:
Civil service departments in London (Whitehall II study; study inception 1985-88).
PARTICIPANTS:
7899 participants with data on the cardiovascular health score at age 50.
EXPOSURES:
The cardiovascular health score included four behavioural (smoking, diet, physical activity, body mass index) and three biological (fasting glucose, blood cholesterol, blood pressure) metrics, coded on a three point scale (0, 1, 2). The cardiovascular health score was the sum of seven metrics (score range 0-14) and was categorised into poor (scores 0-6), intermediate (7-11), and optimal (12-14) cardiovascular health.
MAIN OUTCOME MEASURE:
Incident dementia, identified through linkage to hospital, mental health services, and mortality registers until 2017.
RESULTS:
347 incident cases of dementia were recorded over a median follow-up of 24.7 years. Compared with an incidence rate of dementia of 3.2 (95% confidence interval 2.5 to 4.0) per 1000 person years among the group with poor cardiovascular health, the absolute rate differences per 1000 person years were -1.5 (95% confidence interval -2.3 to -0.7) for the group with intermediate cardiovascular health and -1.9 (-2.8 to -1.1) for the group with optimal cardiovascular health. Higher cardiovascular health score was associated with a lower risk of dementia (hazard ratio 0.89 (0.85 to 0.95) per 1 point increment in the cardiovascular health score). Similar associations with dementia were observed for the behavioural and biological subscales (hazard ratios per 1 point increment in the subscores 0.87 (0.81 to 0.93) and 0.91 (0.83 to 1.00), respectively). The association between cardiovascular health at age 50 and dementia was also seen in people who remained free of cardiovascular disease over the follow-up (hazard ratio 0.89 (0.84 to 0.95) per 1 point increment in the cardiovascular health score).
CONCLUSION:
Adherence to the Life Simple 7 ideal cardiovascular health recommendations in midlife was associated with a lower risk of dementia later in life.

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Variation of all-cause and cause-specific mortality with body mass index in one million Swedish parent-son pairs: An instrumental variable analysis.
Wade KH, Carslake D, Tynelius P, Davey Smith G, Martin RM.
PLoS Med. 2019 Aug 9;16(8):e1002868. doi: 10.1371/journal.pmed.1002868. eCollection 2019 Aug.
PMID: 31398184
Abstract
BACKGROUND:
High body mass index (BMI) is associated with mortality, but the pervasive problem of confounding and reverse causality in observational studies limits inference about the direction and magnitude of causal effects. We aimed to obtain estimates of the causal association of BMI with all-cause and cause-specific mortality.
METHODS AND FINDINGS:
In a record-linked, intergenerational prospective study from the general population of Sweden, we used two-sample instrumental variable (IV) analysis with data from 996,898 fathers (282,407 deaths) and 1,013,083 mothers (153,043 deaths) and their sons followed up from January 1, 1961, until December 31, 2004. Sons' BMI was used as the instrument for parents' BMI to compute hazard ratios (HRs) for risk of mortality per standard deviation (SD) higher parents' BMI. Using offspring exposure as an instrument for parents' exposure is unlikely to be affected by reverse causality (an important source of bias in this context) and reduces confounding. IV analyses supported causal associations between higher BMI and greater risk of all-cause mortality (HR [95% confidence interval (CI)] per SD higher fathers' BMI: 1.29 [1.26-1.31] and mothers' BMI: 1.39 [1.35-1.42]) and overall cancer mortality (HR per SD higher fathers' BMI: 1.20 [1.16-1.24] and mothers' BMI: 1.29 [1.24-1.34]), including 9 site-specific cancers in men (bladder, colorectum, gallbladder, kidney, liver, lung, lymphatic system, pancreas, and stomach) and 11 site-specific cancers in women (gallbladder, kidney, liver, lung, lymphatic system, ovaries, pancreas, stomach, uterus, cervix, and endometrium). There was evidence supporting causal associations between higher BMI in mothers and greater risk of mortality from kidney disease (HR: 2.17 [1.68-2.81]) and lower risk of mortality from suicide (HR: 0.77 [0.65-0.90]). In both sexes, there was evidence supporting causal associations between higher BMI and mortality from cardiovascular diseases (CVDs), stroke, diabetes, and respiratory diseases. We were unable to test the association between sons' and mothers' BMIs (as mothers' data were unavailable) or whether the instrument was independent of unmeasured or residual confounding; however, the associations between parents' mortality and sons' BMI were negligibly influenced by adjustment for available confounders.
CONCLUSIONS:
Consistent with previous large-scale meta-analyses and reviews, results supported the causal role of higher BMI in increasing the risk of several common causes of death, including cancers with increasing global incidence. We also found positive effects of BMI on mortality from respiratory disease, prostate cancer, and lung cancer, which has been inconsistently reported in the literature, suggesting that the causal role of higher BMI in mortality from these diseases may be underestimated. Furthermore, we expect different patterns of bias in the current observational and IV analyses; therefore, the similarities between our findings from both methods increases confidence in the results. These findings support efforts to understand the mechanisms underpinning these effects to inform targeted interventions and develop population-based strategies to reduce rising obesity levels for disease prevention.

Co-ingestion of Black Tea Reduces the Indispensable Amino Acid Digestibility of Hens' Egg in Indian Adults.
Kashyap S, Shivakumar N, Varkey A, Preston T, Devi S, Kurpad AV.
J Nutr. 2019 Aug 1;149(8):1363-1368. doi: 10.1093/jn/nxz091.
PMID: 31127832 Free PMC Article
Abstract
BACKGROUND:
Tea, a commonly consumed beverage, contains high amounts of polyphenols that can impair protein digestibility, as demonstrated in vitro. There are no human studies examining the inhibitory influence of tea polyphenols (TPP) on high-quality protein digestibility.
OBJECTIVE:
The aim of this study was to determine the effect of black tea on the true indispensable amino acid (IAA) digestibility of whole boiled egg protein, in healthy adult humans, through use of a dual isotope tracer approach.
METHODS:
The effect of black TPP (4.6 mg/mL, ingested as a beverage with the meal) on 2H-labeled whole boiled egg protein, administered with ghee rice and tomato curry, was measured with reference to 13C-spirulina protein in healthy Indian adults aged 20-27 y of both sexes with BMI of 22.0 ± 2.8 kg/m2. The results were then compared to previously determined whole egg mean IAA digestibility measured by the same method, without black tea, in the same subjects (n = 5). To correct for any independent effect of TPP on spirulina protein (used as a standard protein), the true IAA digestibility of 13C-spirulina protein was independently measured with reference to a 2H-amino acid mixture, with and without co-ingestion of black tea, in 3 of the same subjects.
RESULTS:
The true IAA digestibility of whole boiled egg protein significantly decreased by 17% when co-ingested with black tea. However, there was no significant reduction in the true IAA digestibility of spirulina protein when co-ingested with black tea.
CONCLUSIONS:
TPP protein interactions reduced whole egg digestibility in healthy Indian adults but had minimal effect on spirulina protein digestibility. In populations who are at risk of dietary quality protein inadequacy, the consumption of tea during or after a meal can further increase the risk of inadequacy.
KEYWORDS:
black tea; dual isotope tracer technique; intrinsically labeled egg; tea polyphenol; true indispensable amino acid digestibility

Intake of Dietary Fiber, Fruits, and Vegetables and Risk of Diverticulitis.
Ma W, Nguyen LH, Song M, Jovani M, Liu PH, Cao Y, Tam I, Wu K, Giovannucci EL, Strate LL, Chan AT.
Am J Gastroenterol. 2019 Aug 7. doi: 10.14309/ajg.0000000000000363. [Epub ahead of print]
PMID: 31397679
Abstract
OBJECTIVES:
Although low fiber intake has been considered a risk factor for diverticulitis, prospective evidence is limited in women despite having a disproportionate burden of disease, with little known about variation in the protective effects according to food sources. We assessed the associations of intakes of fiber and major food sources of fiber including fruits and vegetables with risk of diverticulitis in a large cohort of women.
METHODS:
We followed 50,019 women in the Nurses' Health Study (1990-2014) who were aged 43-70 years and free of diverticulitis, cancer, and inflammatory bowel disease at baseline. Incident diverticulitis was identified through self-report with validity confirmed by review of medical records.
RESULTS:
We documented 4,343 incident cases of diverticulitis, encompassing 1,106,402 person-years of follow-up. Compared with participants in the lowest quintile, the multivariable hazard ratio of diverticulitis in the highest quintile of total fiber intake was 0.86 (95% confidence interval: 0.78-0.95; P-trend = 0.002). Fiber from fruits and cereals, but not vegetables, was associated with a decreased risk of diverticulitis. Furthermore, intake of total whole fruit intake and specific fruits such as apples/pears and prunes were associated with reduced risk of diverticulitis with a multivariable hazard ratio for diverticulitis of 0.95 (0.92-0.98; P-trend < 0.001) for every serving increase of total whole fruit intake per day.
DISCUSSION:
Higher intake of dietary fiber and fiber from different food sources, except for vegetable fiber, are associated with a lower risk of diverticulitis in women. A greater intake of whole fruit is also associated with reduced risk.

Chronic Consumption of a Commercial Energy Drink Reduces Blood Pressure in Normotensive Wild-Type Mice.
Graneri L, D'Alonzo Z, Lam V, Mamo J, Dhaliwal S, Takechi R.
Front Nutr. 2019 Jul 23;6:111. doi: 10.3389/fnut.2019.00111. eCollection 2019.
PMID: 31396518
Abstract
Objective: Studies report that acute consumption of energy drinks transiently increases blood pressure (BP). However, few studies report the effect of chronic energy drink consumption on BP. In this study, we investigated the effects of long-term energy drink ingestion on BP in C57BL/6J normotensive wild-type mice. Research Methods and Procedures: Groups of mice were randomized to no treatment (water) (Control group), or to Mother™ provided as a decarbonated 30% (v/v) drinking solution (Energy Drink group), sugar-free Mother™ at 30% (Sugar-free group), Coca Cola™ at 30% (Coke group) for a total intervention period of 13 weeks. Results: After 13 weeks of intervention, the control mice showed a modest increase in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) by 7.1 ± 8.8, 5.8 ± 9.4, and 6.3 ± 9.1 mmHg, respectively. However, the Energy Drink significantly decreased the DBP and MAP by 18.8 ± 9.9 and 15.3 ± 9.8 mmHg, respectively. Similarly, Sugar-free group mice showed significant decrease of the SBP, DBP, and MAP by 10.85 ± 5.6, 18.7 ± 6.7, and 15.6 ± 6.1 mmHg, respectively. The SBP, DBP, and MAP in Coke mice showed no significant changes. The estimated cumulative intake of caffeine, taurine, and vitamin B3 and B5 was significantly higher in the mice of Energy Drink and Sugar-free groups compared to the Control and Coke mice. Conclusion: Collectively, the data suggest that the long-term chronic consumption of energy drinks may significantly lower the BP in normotensive mice through the actions of caffeine, taurine, and/or B-vitamins. The study findings do not support consideration of energy drinks for BP management, but rather demonstrate no long-term amplification of BP in normotensive preclinical models.
KEYWORDS:
blood pressure; caffeine; coke; energy drink; sugar free energy drink; taurine; vitamin B

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Association of BMI, smoking and alcohol with multiple myeloma mortality in Asians: a pooled analysis of more than 800,000 participants in the Asia Cohort Consortium.
Ugai T, Ito H, Oze I, Saito E, Rahman MS, Boffetta P, Gupta PC, Sawada N, Tamakoshi A, Shu XO, Koh WP, Gao YT, Sadakane A, Tsuji I, Park SK, Nagata C, You SL, Pednekar MS, Tsugane S, Cai H, Yuan JM, Xiang YB, Ozasa K, Tomata Y, Kanemura S, Sugawara Y, Wada K, Chen CJ, Yoo KY, Chia KS, Ahsan H, Zheng W, Inoue M, Kang D, Potter JD, Matsuo K.
Cancer Epidemiol Biomarkers Prev. 2019 Aug 9. pii: cebp.0389.2019. doi: 10.1158/1055-9965.EPI-19-0389. [Epub ahead of print]
PMID: 31399476
Abstract
BACKGROUND:
To date, few epidemiological studies have been conducted to elucidate lifestyle-related risk factors for multiple myeloma (MM) in Asia. We investigated the association of body mass index (BMI), smoking, and alcohol intake with the risk of MM mortality through a pooled analysis of more than 800,000 participants in the Asia Cohort Consortium.
METHODS:
The analysis included 805,309 participants contributing 10,221,623 person-years of accumulated follow-up across Asia Cohort Consortium cohorts. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between BMI, smoking and alcohol at baseline and the risk of MM mortality were assessed using a Cox proportional hazards model with shared frailty.
RESULTS:
We observed a statistically significant dose-dependent association between BMI categories and the risk of MM mortality (<18.5 kg/m2: HR=0.80, 95% CI: 0.52-1.24; 18.5 to 24.9 kg/m2: reference; 25.0 to 29.9 kg/m2: HR=1.17, 0.94-1.47; ≥30 kg/m2: HR=1.61, 0.99-2.64, p for trend=0.014). By sex, this association was more apparent in women than in men (P for heterogeneity between sexes=0.150). We observed no significant associations between smoking or alcohol consumption and risk of MM mortality.
CONCLUSION:
This study showed that excess body mass is associated with an increased risk of MM mortality among Asian populations. In contrast, our results do not support an association between smoking or alcohol consumption and the risk of MM mortality in Asian populations.
IMPACT:
This study provides important evidence on the association of BMI, smoking and alcohol with the risk of MM mortality in Asian populations.

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Trajectories of body mass index in adulthood and all-cause and cause-specific mortality in the Melbourne Collaborative Cohort Study.
Yang Y, Dugué PA, Lynch BM, Hodge AM, Karahalios A, MacInnis RJ, Milne RL, Giles GG, English DR.
BMJ Open. 2019 Aug 10;9(8):e030078. doi: 10.1136/bmjopen-2019-030078.
PMID: 31401610
https://bmjopen.bmj.com/content/9/8/e030078.long
https://bmjopen.bmj.com/content/bmjopen/9/8/e030078.full.pdf
Abstract
OBJECTIVE:
Limited research has assessed the association between patterns of body mass index (BMI) change across adulthood and mortality. We aimed to identify groups of individuals who followed specific group-based BMI trajectories across adulthood, using weight collected on three occasions and recalled data from early adulthood, and to examine associations with all-cause and cause-specific mortality.
DESIGN:
Prospective cohort study.
SETTING:
Melbourne, Australia.
PARTICIPANTS:
Adults (n=29 881) enrolled in the Melbourne Collaborative Cohort Study, who were aged from 40 to 70 years between 1990 and 1994, and had BMI data for at least three time points.
OUTCOME:
Deaths from any cause before 31 March 2017 and deaths from obesity-related cancers, cardiovascular diseases (CVDs) and other causes before 31 December 2013.
RESULTS:
We identified six group-based BMI trajectories: lower-normal stable (TR1), higher-normal stable (TR2), normal to overweight (TR3), chronic borderline obesity (TR4), normal to class I obesity (TR5) and overweight to class II obesity (TR6). Generally, compared with maintaining lower-normal BMI throughout adulthood, the lowest mortality was experienced by participants who maintained higher-normal BMI (HR 0.90; 95% CI 0.84 to 0.97); obesity during midlife was associated with higher all-cause mortality even when BMI was normal in early adulthood (HR 1.09; 95% CI 0.98 to 1.21) and prolonged borderline obesity from early adulthood was also associated with elevated mortality (HR 1.16; 95% CI 1.01 to 1.33). These associations were stronger for never-smokers and for death due to obesity-related cancers. Being overweight in early adulthood and becoming class II obese was associated with higher CVD mortality relative to maintaining lower-normal BMI (HR 2.27; 95% CI 1.34 to 3.87).
CONCLUSION:
Our findings highlight the importance of weight management throughout adulthood to reduce mortality.
KEYWORDS:
epidemiology; preventive medicine; public health

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General and Abdominal Adiposity and Mortality in Mexico City: Prospective Study of 150 000 Adults.
Gnatiuc L, Alegre-Díaz J, Wade R, Ramirez-Reyes R, Tapia-Conyer R, Garcilazo-Ávila A, Chiquete E, Gonzáles-Carballo C, Solano-Sanchez M, Clarke R, Collins R, Herrington WG, Hill M, Lewington S, Peto R, Emberson JR, Kuri-Morales P.
Ann Intern Med. 2019 Aug 13. doi: 10.7326/M18-3502. [Epub ahead of print]
PMID: 31404923
Abstract
BACKGROUND:
Some reports suggest that body mass index (BMI) is not strongly associated with mortality in Hispanic populations.
OBJECTIVE:
To assess the causal relevance of adiposity to mortality in Mexican adults, avoiding reverse causality biases.
DESIGN:
Prospective study.
SETTING:
2 Mexico City districts.
PARTICIPANTS:
159 755 adults aged 35 years and older at recruitment, followed for up to 14 years. Participants with a hemoglobin A1c level of 7% or greater, diabetes, or other chronic diseases were excluded.
MEASUREMENTS:
BMI, waist-to-hip ratio, waist circumference, and cause-specific mortality. Cox regression, adjusted for confounders, yielded mortality hazard ratios (HRs) after at least 5 years of follow-up and before age 75 years.
RESULTS:
Among 115 400 participants aged 35 to <75 years at recruitment, mean BMI was 28.0 kg/m2 (SD, 4.1 kg/m2) in men and 29.6 kg/m2 (SD, 5.1 kg/m2) in women. The association of BMI at recruitment with all-cause mortality was J-shaped, with the minimum at 25 to <27.5 kg/m2. Above 25 kg/m2, each 5-kg/m2 increase in BMI was associated with a 30% increase in all-cause mortality (HR, 1.30 [95% CI, 1.24 to 1.36]). This association was stronger at ages 40 to <60 years (HR, 1.40 [CI, 1.30 to 1.49]) than at ages 60 to <75 years (HR, 1.24 [CI, 1.17 to 1.31]) but was not materially affected by sex, smoking, or other confounders. The associations of mortality with BMI and waist-to-hip ratio were similarly strong, and each was weakened only slightly by adjustment for the other. Waist circumference was strongly related to mortality and remained so even after adjustment for BMI and hip circumference.
LIMITATIONS:
Analyses were limited to mortality.
CONCLUSION:
General, and particularly abdominal, adiposity were strongly associated with mortality in this Mexican population.

Heart rate and premature atrial contractions at 24hECG independently predict atrial fibrillation in a population-based study.
Persson AP, Fedorowski A, Hedblad B, Persson M, Juul-Möller S, Engström G, Johnson LSB.
Heart. 2019 Aug 12. pii: heartjnl-2019-315119. doi: 10.1136/heartjnl-2019-315119. [Epub ahead of print]
PMID: 31405897
Abstract
BACKGROUND:
Low resting heart rate and premature atrial contractions (PACs) predict incident atrial fibrillation (AF) and could be interdependent, since PACs occur in the gaps between normal beats.
OBJECTIVE:
To study the association between low heart rate at 24hECG, PACs and incident AF in a prospective population-based cohort.
METHODS:
In the Malmö Diet and Cancer study, 24hECGs were performed in 377 AF-free subjects. The endpoint was clinical AF retrieved from national hospital (mean follow-up 17 years). The interaction between increased supraventricular activity (SVA) top quartile of either PACs/hour or supraventricular tachycardias/hour) and mean heart rate (mHR) as regards AF risk was assessed in multivariable Cox regression analyses adjusted for age, sex, height, BMI, systolic blood pressure, antihypertensive medication, smoking and homeostasis model assessment of insulin resistance.
RESULTS:
There were 80 (21%) incident cases of AF. Below median mHR (80 bpm/75 bpm for women/men) was associated with increased AF incidence (HR: 1.89, 95% CI 1.18 to 3.02, p=0.008). There was no correlation between mHR and SVA (p=0.6) or evidence of a multiplicative interaction between these factors for AF risk (p for interaction=0.6) In the group with both increased SVA and below median mHR (17% of the population) the relative risk of AF was very high (HR 4.5, 95% CI 2.2 to 9.1, p=0.001).
CONCLUSION:
Low mHR at 24hECG independently predicts AF, but there is no association between mHR and SVA, and these factors are independent as regards AF risk. Subjects with both low mHR and increased SVA have high AF risk.
KEYWORDS:
24h-electrocardiogram; atrial fibrillation; heartrate; population; supraventricular ectopy, premature atrial contraction

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Postprandial Responses of Serum Bile Acids in Healthy Humans After Ingestion of Turmeric Before Medium /High-Fat Breakfasts.
Ghaffarzadegan T, Zanzer YC, Östman E, Hållenius F, Essén S, Sandahl M, Nyman M.
Mol Nutr Food Res. 2019 Aug 14:e1900672. doi: 10.1002/mnfr.201900672. [Epub ahead of print]
PMID: 31411373
https://sci-hub.tw/10.1002/mnfr.201900672
Abstract
SCOPE:
Bile acids (BAs) are known to regulate a number of metabolic activities in the body. However, very little is known about how BAs are affected by diet. This study aimed to investigate whether a single-dose of turmeric-based beverage (TUR) before ingestion of medium- (MF) or high-fat (HF) breakfasts would improve the BA profile in healthy subjects.
METHODS AND RESULTS:
Twelve healthy subjects were assigned to a randomized crossover single-blind study. The subjects received iso-caloric MF or HF breakfasts after a drink containing flavored water with or without an extract of turmeric with at least one-week wash-out period between the treatments. Postprandial BAs were measured using protein precipitation followed by ultra-high-performance liquid chromatography-mass spectrometry analysis (UHPLC-MS). The concentration of BAs was generally higher after HF than MF breakfasts. Ingestion of TUR before MF breakfast increased the serum concentrations of free and conjugated forms of cholic and ursodeoxycholic acids, as well as the concentrations of chenodeoxycholic acid and its taurine-conjugated form. However, the concentration of conjugated forms of deoxycholic acid decreased when TUR was taken before HF breakfast.
CONCLUSION:
TUR ingestion before MF and HF breakfasts improved BA profiles and may therefore have potential health-promoting effects on BA metabolism.
KEYWORDS:
Curcumin; mass spectrometry; postprandial bile acids; turmeric; ultra-high-performance liquid chromatography

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Polyphenols and Metabolites Enhance Survival in Rodents and Nematodes-Impact of Mitochondria.
Dilberger B, Passon M, Asseburg H, Silaidos CV, Schmitt F, Schmiedl T, Schieber A, Eckert GP.
Nutrients. 2019 Aug 13;11(8). pii: E1886. doi: 10.3390/nu11081886.
PMID: 31412639
https://www.mdpi.com/2072-6643/11/8/1886/htm
Abstract
(1) Background: Polyphenols (PP) play an important role in the prevention of non-communicable diseases and may contribute to healthy aging. To investigate the molecular and cellular aspects of PP metabolites on longevity with a focus on mitochondrial function, we applied a pre-fermented mixture of polyphenols (Rechtsregulat®, RR) to rodents and nematodes. (2) Methods: The lifespans of Navar Medical Research Institute (NMRI) mice and C. elegans were recorded. The heat-stress resistance (37 °C) of C. elegans N2 was measured using nucleic staining. Respiration and membrane potential (ΔΨm) were measured in isolated mitochondria. The energetic metabolites adenosine triphosphate (ATP), lactate, and pyruvate were determined in lysates. Expression levels of longevity related genes were determined using quantitative real time polymerase chain reaction (qRT-PCR). Phenolic compounds were identified using ultra high performance liquid chromatography-diode array detection-Iontrap-multiple stage mass spectrometry (UHPLC-DAD-Iontrap-MSn). (3) Results: Several phenolic metabolites including protocatechuic acid (PCA) were identified in RR. Feeding of mice with RR resulted in a significantly increased lifespan. Heat-stress resistance (RR *** p = 0.0006; PCA **** p < 0.0001), median lifespan (NMRI: RR ** p = 0.0035; C. elegans RR * p = 0.0279; PCA **** p < 0.0001), and activity of mitochondrial respiratory chain complexes (RR *-** p = 0.0237 - 0.0052; PCA * p = 0.019 - 0.0208) of C. elegans were significantly increased after incubation with RR (10%) or PCA (780 µM). PCA significantly improved nematodes ΔΨm (* p = 0.02058) and ATP levels (* p = 0.029). RR significantly up-regulated lactate levels, indicating enhanced glycolysis. The expression levels of longevity related genes daf-16, sir-2.1, and skn-1 were significantly upregulated after PCA, and partially after RR administration. (4) Conclusion: Phenolic metabolites such as PCA have the potential to enhance health and lifespan and mitochondrial function, and thus may contribute to healthy aging.
KEYWORDS:
caenorhabditis elegans; longevity; mitochondria; polyphenol; protocatechuic acid; respiration

Improvement of cognitive functions by oral intake of Hericium erinaceus.
Saitsu Y, Nishide A, Kikushima K, Shimizu K, Ohnuki K.
Biomed Res. 2019;40(4):125-131. doi: 10.2220/biomedres.40.125.
PMID: 31413233
Abstract
Hericium erinaceus has been recognized as medical mushroom since ancient time, but its scientific evidence for human health has been still uncertain. In this study, we tested a randomized, double-blind, placebo-controlled parallel-group comparative study to evaluate the improvement of the cognitive functions by taking supplements containing fruiting body of H. erinaceus for 12 weeks. We performed three kinds of tests: Mini Mental State Examination (MMSE), Benton visual retention test, and Standard verbal paired-associate learning test (S-PA). MMSE alone showed that oral intake of H. erinaceus significantly improved cognitive functions and prevented from the deterioration. We speculate that various chemical compounds, including hericenones, in the mushroom have multiple effects to the brain neural networks and improve cognitive functions. Oral intake of H.erinaceus is safe and convenient method for dementia prevention so far.
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https://www.crsociety.org/topic/11801-als-papers-citations-and-possibly-links-and-excerpts-or-my-synopses/?page=7&tab=comments#comment-20947

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