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

[AlPater]

The importance of stroke as a risk factor of cognitive decline in community dwelling older and oldest peoples: the SONIC study.
Srithumsuk W, Kabayama M, Gondo Y, Masui Y, Akagi Y, Klinpudtan N, Kiyoshige E, Godai K, Sugimoto K, Akasaka H, Takami Y, Takeya Y, Yamamoto K, Ikebe K, Ogawa M, Inagaki H, Ishizaki T, Arai Y, Rakugi H, Kamide K.
BMC Geriatr. 2020 Jan 22;20(1):24. doi: 10.1186/s12877-020-1423-5.
PMID: 31969126
Abstract
BACKGROUND:
Cognitive impairment is a major health concern among older and oldest people. Moreover, stroke is a relevant contributor for cognitive decline and development of dementia. The study of cognitive decline focused on stroke as the important risk factor by recruiting older and oldest is still lagging behind. Therefore, the aim of this study was to investigate the importance of stroke as a risk factor of cognitive decline during 3 years in community dwelling older and oldest people.
METHODS:
This study was longitudinal study with a 3-year follow-up in Japan. The participants were 1333 community dwelling older and oldest people (70 years old = 675, 80 years old = 589, and 90 years old = 69). Data collected included basic data (age, sex, and history of stroke), vascular risk factors (hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, and current smoking), and social factors (educational level, frequency of going outdoors, long-term care (LTC) service used, and residential area). The Japanese version of the Montreal Cognitive Assessment (MoCA-J) was decline of ≥2 points was defined as cognitive decline. Multiple logistic regression analysis was used to investigate the association between stroke and other risk factors with cognitive decline during a 3-year follow-up.
RESULTS:
The fit of the hypothesized model by multiple logistic regression showed that a history of stroke, advanced age, and greater MoCA-J score at the baseline were important risk factors, while the presence of dyslipidemia and a higher educational level were protective factors that were significantly correlated with cognitive decline during the 3-year follow-up.
CONCLUSIONS:
The cognitive decline after the 3-year follow-up was influenced by the history of stroke and advanced age, while greater MoCA-J score at the baseline was positively associated with subsequent 3 years cognitive decline. The protective factors were the presence of dyslipidemia and a higher educational level. Therefore, these factors are considered important and should be taken into consideration when searching for creative solutions to prevent cognitive decline after stroke in community dwelling older and oldest people.
KEYWORDS:
Cognitive decline; Older and oldest people; Stroke

Metabolites associated with walking ability among the oldest old from the CHS All Stars study.
Marron MM, Wendell SG, Boudreau RM, Clish CB, Santanasto AJ, Tseng GC, Zmuda JM, Newman AB.
J Gerontol A Biol Sci Med Sci. 2020 Jan 23. pii: glaa030. doi: 10.1093/gerona/glaa030. [Epub ahead of print]
PMID: 31970383
Abstract
BACKGROUND:
Low walking ability is highly prevalent with advancing age and predicts major health outcomes. Metabolomics may help to better characterize differences in walking ability among older adults, providing insight into potentially altered molecular processes underlying age-related decline in functioning. We sought to identify metabolites and metabolic pathways associated with high versus low walking ability among 120 participants ages 79-95 from the CHS All Stars study.
METHODS:
Using a nested case-control design, 60 randomly selected participants with low walking ability were matched one-to-one on age, gender, race, and fasting time with 60 participants with high walking ability. High versus low walking ability was defined as being in the best versus worst tertiles for both gait speed (≥0.9 versus <0.7m/s) and the Walking Ability Index (7-9 versus 0-1). Using liquid chromatography-mass spectrometry, 569 metabolites were identified in overnight-fasting plasma.
RESULTS:
Ninety-six metabolites were associated with walking ability, where 24% were triacylglycerols. Triacylglycerols that were higher among those with high walking ability consisted mostly of polyunsaturated fatty acids, whereas triacylglycerols that were lower among those with high walking ability consisted mostly of saturated or monounsaturated fatty acids. Body composition partly explained associations between some metabolites and walking ability. Proline and arginine metabolism was a top pathway associated with walking ability.
CONCLUSION:
These results may partly reflect pathways of modifiable risk factors, including excess dietary lipids and lack of physical activity, contributing to obesity and further alterations in metabolic pathways that lead to age-related decline in walking ability in this older adult cohort.
KEYWORDS:
Gait speed; Lipids; Metabolomics; Triacylglycerols

Yogurt Intake Reduces All-Cause and Cardiovascular Disease Mortality: A Meta-Analysis of Eight Prospective Cohort Studies.
Gao X, Jia HY, Chen GC, Li CY, Hao M.
Chin J Integr Med. 2020 Jan 22. doi: 10.1007/s11655-020-3085-8. [Epub ahead of print]
PMID: 31970674
Abstract
OBJECTIVE:
To assess the relationship between yogurt intake and mortality risk from prospective cohort studies.
METHODS:
The PubMed, EMBASE, and Web of Science databases were searched for all records related to yogurt intake and mortality risk [all-cause or cardiovascular disease (CVD) or cancer mortality] before October 1, 2018. The Newcastle-Ottawa Quality Scale was used to estimate the quality of all eligible articles. The results of the highest and lowest categories of yogurt intake in each study were collected and the effect size was pooled using a random effects model. The dose-response analysis was calculated using the generalized least squares trend estimation model.
RESULTS:
Eight eligible cohort studies were included in this meta-analysis. There were 235,676 participants in the 8 studies, and the number of deaths was 14,831. Compared with the lowest category, the highest category of yogurt intake was not significantly related with all-cause mortality [hazard ratio (HR)=0.93; 95% confidence interval (CI): 0.85, 1.01], CVD mortality (HR=0.92; 95% CI: 0.81, 1.03) and cancer mortality (HR=0.97; 95% CI: 0.83, 1.12). These studies were homogenous, since the homogeneity test showed that I2 was 28.7%, 15.1% and 11.8%, respectively. However, yogurt intake ⩾200 g/d was significantly associated with a lower all-cause mortality (HR=0.88; 95% CI: 0.80, 0.96) and CVD mortality (HR=0.87; 95% CI: 0.77, 0.99) in the subgroup analysis. The dose-response analysis showed that yogurt intake of 200 g/d was inversely associated with all-cause mortality (P=0.041, HR=0.95, 95% CI: 0.92, 1.00) and CVD mortality (P=0.009, HR=0.92, 95% CI: 0.86, 0.98), and all of which were linear relationship (P>0.05).
CONCLUSIONS:
This review provided the evidence regarding yogurt intake can reduce all-cause and CVD mortality. Although some positive findings were identified, more high-quality cohort studies and randomized controlled trials are warranted on a possible protective effect of yoghurt on health.
KEYWORDS:
cancer; cardiovascular disease; meta-analysis; mortality; yogurt

The Effect of High Carbohydrate-to-fat Intake Ratios on Hypo-HDL-cholesterolemia Risk and HDL-cholesterol Levels over a 12-year Follow-up.
Lee HA, An H.
Sci Rep. 2020 Jan 22;10(1):913. doi: 10.1038/s41598-020-57931-w.
PMID: 31969639
Abstract
Considering the strong correlation between carbohydrate and fat intake, we defined and assessed the association of the carbohydrate-to-fat ratio with the high-density lipoprotein cholesterol (HDL-c) level using 12-year follow-up data from the community-based cohort of the Korean Genome Epidemiology Study. We evaluated the long-term changes in HDL-c levels according to quartiles of carbohydrate-to-fat ratio using a mixed model. We also assessed the effect of the carbohydrate-to-fat ratio on the prevalence and incidence of hypo-HDL-cholesterolemia. Of 6,627 subjects, the prevalence of undiagnosed hypo-HDL-cholesterolemia at baseline was 35.3% (n = 2,339). Among the disease-free subjects, 56.8% developed hypo-HDL-cholesterolemia (incidence = 92/1,000 person-years). The prevalence and incidence of hypo-HDL-cholesterolemia were higher in females than in males. The highest carbohydrate-to-fat ratio quartile, which was characterized by high and low intake of carbohydrate and fat, was consistently associated with a lower HDL-c level during the 12-year follow up. Moreover, those in the highest quartile had a 1.14-fold greater risk of incident hypo-HDL-cholesterolemia than those in the lowest quartile, with a significant dose-response relationship. We found that high and low intake of carbohydrate and fat, respectively, was consistently associated with a low HDL-c level over a prolonged period. More research is needed to promote appropriate intake of macronutrients.

Association of egg intake with blood lipids, cardiovascular disease, and mortality in 177,000 people in 50 countries.
Dehghan M, Mente A, Rangarajan S, Mohan V, Lear S, Swaminathan S, Wielgosz A, Seron P, Avezum A, Lopez-Jaramillo P, Turbide G, Chifamba J, AlHabib KF, Mohammadifard N, Szuba A, Khatib R, Altuntas Y, Liu X, Iqbal R, Rosengren A, Yusuf R, Smuts M, Yusufali A, Li N, Diaz R, Yusoff K, Kaur M, Soman B, Ismail N, Gupta R, Dans A, Sheridan P, Teo K, Anand SS, Yusuf S.
Am J Clin Nutr. 2020 Jan 21. pii: nqz348. doi: 10.1093/ajcn/nqz348. [Epub ahead of print]
PMID: 31965140
Abstract
BACKGROUND:
Eggs are a rich source of essential nutrients, but they are also a source of dietary cholesterol. Therefore, some guidelines recommend limiting egg consumption. However, there is contradictory evidence on the impact of eggs on diseases, largely based on studies conducted in high-income countries.
OBJECTIVES:
Our aim was to assess the association of egg consumption with blood lipids, cardiovascular disease (CVD), and mortality in large global studies involving populations from low-, middle-, and high-income countries.
METHODS:
We studied 146,011 individuals from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. Egg consumption was recorded using country-specific validated FFQs. We also studied 31,544 patients with vascular disease in 2 multinational prospective studies: ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global End Point Trial) and TRANSCEND (Telmisartan Randomized Assessment Study in ACEI Intolerant Subjects with Cardiovascular Disease). We calculated HRs using multivariable Cox frailty models with random intercepts to account for clustering by study center separately within each study.
RESULTS:
In the PURE study, we recorded 14,700 composite events (8932 deaths and 8477 CVD events). In the PURE study, after excluding those with history of CVD, higher intake of egg (≥7 egg/wk compared with <1 egg/wk intake) was not significantly associated with blood lipids, composite outcome (HR: 0.96; 95% CI: 0.89, 1.04; P-trend = 0.74), total mortality (HR: 1.04; 95% CI: 0.94, 1.15; P-trend = 0.38), or major CVD (HR: 0.92; 95% CI: 0.83, 1.01; P-trend = 0.20). Similar results were observed in ONTARGET/TRANSCEND studies for composite outcome (HR 0.97; 95% CI: 0.76, 1.25; P-trend = 0.09), total mortality (HR: 0.88; 95% CI: 0.62, 1.24; P-trend = 0.55), and major CVD (HR: 0.97; 95% CI: 0.73, 1.29; P-trend = 0.12).
CONCLUSIONS:
In 3 large international prospective studies including ∼177,000 individuals, 12,701 deaths, and 13,658 CVD events from 50 countries in 6 continents, we did not find significant associations between egg intake and blood lipids, mortality, or major CVD events.
KEYWORDS:
blood lipids; cardiovascular disease; dietary cholesterol; egg intake; mortality

Associations of n-3, n-6 Fatty Acids Intakes and n-6:n-3 Ratio with the Risk of Depressive Symptoms: NHANES 2009-2016.
Zhang R, Sun J, Li Y, Zhang D.
Nutrients. 2020 Jan 16;12(1). pii: E240. doi: 10.3390/nu12010240.
PMID: 31963375
Abstract
Many studies have explored the association between n-3 fatty acids and depression, but research on the associations of n-6 fatty acids and n-6:n-3 ratio with depression is more scarce, and the results are controversial. Therefore, we conducted this cross-sectional study to explore the associations of n-3 and n-6 fatty acid intakes and n-6:n-3 ratio with the risk of depressive symptoms using data from National Health and Nutrition Examination Survey (NHANES) 2009-2016. Dietary data on n-3 and n-6 fatty acids were obtained through two 24-h dietary recall interviews, and were adjusted by energy. Depressive symptoms were measured by PHQ-9 (nine-item Patient Health Questionnaire). We applied logistic regression and restricted cubic spline models to assess the relationships of n-3 and n-6 fatty acids intake and n-6:n-3 ratio with the risk of depressive symptoms. A total of 17,431 individuals over 18 years old were enrolled in this study. In the multivariate-adjusted model 2, compared with the lowest category, the highest odd ratios (ORs) with 95% confidence intervals (CIs) for n-3 fatty acid intake and n-6:n-3 ratio were 0.71 (0.55-0.92) and 1.66 (1.10-2.50), and middle OR (95% CI) for n-6 fatty acid intake was 0.72 (0.56-0.92), respectively. Our study suggests that n-3 and n-6 fatty acids intake were inversely associated with the risk of depressive symptoms, while the n-6:n-3 ratio was positively associated with the risk of depressive symptoms.
KEYWORDS:
depressive symptoms; dose-response; n-3 fatty acids; n-6 fatty acids; n-6:n-3 ratio

Association of Blood Pressure Patterns in Young Adulthood With Cardiovascular Disease and Mortality in Middle Age.
Yano Y, Reis JP, Lewis CE, Sidney S, Pletcher MJ, Bibbins-Domingo K, Navar AM, Peterson ED, Bancks MP, Kanegae H, Gidding SS, Muntner P, Lloyd-Jones DM.
JAMA Cardiol. 2020 Jan 22. doi: 10.1001/jamacardio.2019.5682. [Epub ahead of print]
PMID: 31968050
Abstract
IMPORTANCE:
Determining blood pressure (BP) patterns in young adulthood that are associated with cardiovascular disease (CVD) events in later life may help to identify young adults who have an increased risk for CVD.
OBJECTIVE:
To determine whether the long-term variability of BP across clinical visits and the rate of change in BP from young adulthood to midlife are associated with CVD and all-cause mortality by middle age, independently of mean BP during young adulthood and a single BP in midlife.
DESIGN, SETTING, AND PARTICIPANTS:
This prospective cohort study included a community-based sample of 3394 African American and white participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, enrolled from March 1985 through June 1986. Patterns of systolic BP (SBP) were evaluated with measurements at year 0 (baseline) and 2, 5, 7, and 10 years after baseline. Visit-to-visit SBP variability was estimated as BP variability independent of the mean (VIM). Data were collected from March 1985 through August 2015 and analyzed from June through October 2019.
MAIN OUTCOMES AND MEASURES:
Cardiovascular disease and all-cause mortality experienced through August 2015 were adjudicated. The associations of each SBP pattern with CVD events and all-cause mortality were determined using Cox proportional hazards regression models.
RESULTS:
At year 10, the mean (SD) age of the 3394 participants was 35.1 (3.6) years; 1557 (45.9%) were African American; 1892 (55.7%) were women; and 103 (3.0%) were taking antihypertensive medication. During a median follow-up of 20.0 (interquartile range, 19.4-20.2) years, 162 CVD events and 181 deaths occurred. When all BP pattern measurements were entered into the same model including a single SBP measurement at the year 10 examination, the hazard ratios for CVD events for each 1-SD increase in SBP measures were 1.25 (95% CI, 0.90-1.74) for mean SBP, 1.23 (95% CI, 1.07-1.43) for VIM SBP, and 0.99 (95% CI, 0.81-1.26) for annual change of SBP. The VIM for SBP was the only BP pattern associated with all-cause mortality (hazard ratio, 1.24; 95% CI, 1.09-1.41).
CONCLUSIONS AND RELEVANCE:
The results of this study suggest that the assessment of visit-to-visit SBP variability may help identify young adults at increased risk for CVD and all-cause mortality later in life.

Yogurt consumption in relation to mortality from cardiovascular disease, cancer, and all causes: a prospective investigation in 2 cohorts of US women and men.
Schmid D, Song M, Zhang X, Willett WC, Vaidya R, Giovannucci EL, Michels KB.
Am J Clin Nutr. 2020 Jan 22. pii: nqz345. doi: 10.1093/ajcn/nqz345. [Epub ahead of print]
PMID: 31968071
Abstract
BACKGROUND:
Although a link between regular yogurt consumption and mortality appears plausible, data are sparse and have yielded inconsistent results.
OBJECTIVES:
We examined the association between regular yogurt consumption and risk of all-cause and cause-specific mortality among US women and men.
METHODS:
A total of 82,348 women in the Nurses' Health Study and 40,278 men in the Health Professionals Follow-Up Study without a history of cardiovascular disease (CVD) and cancer in 1980 (women) or 1986 (men) were followed up until 2012. Yogurt consumption was assessed by updated validated FFQs.
RESULTS:
During 3,354,957 person-years of follow-up, 20,831 women and 12,397 men died. Compared with no yogurt consumption, the multivariable-adjusted HRs (95% CIs) of mortality were 0.89 (0.86, 0.93), 0.85 (0.81, 0.89), 0.88 (0.84, 0.91), and 0.91 (0.85, 0.98) for ≤1-3 servings/mo, 1 serving/wk, 2-4 servings/wk, and >4 servings/wk in women (P-trend = 0.34), respectively. For men, the corresponding HRs (95% CIs) were 0.99 (0.94, 1.03), 0.98 (0.91, 1.05), 1.04 (0.98, 1.10), and 1.05 (0.95, 1.16), respectively. We further noted inverse associations for cancer mortality (multivariable-adjusted HR comparing extreme categories: 0.87; 95% CI: 0.78, 0.98; P-trend = 0.04) and CVD mortality (HR: 0.92; 95% CI: 0.79, 1.08; P-trend = 0.41) in women, although the latter was attenuated in the multivariable-adjusted model. Replacement of 1 serving/d of yogurt with 1 serving/d of nuts (women and men) or whole grains (women) was associated with a lower risk of all-cause mortality, whereas replacement of yogurt with red meat, processed meat (women and men), and milk or other dairy foods (women) was associated with a greater mortality.
CONCLUSIONS:
In our study, regular yogurt consumption was related to lower mortality risk among women. Given that no clear dose-response relation was apparent, this result must be interpreted with caution.

Red and Processed Meats and Health Risks: How Strong Is the Evidence?
Qian F, Riddle MC, Wylie-Rosett J, Hu FB.
Diabetes Care. 2020 Feb;43(2):265-271. doi: 10.2337/dci19-0063.
PMID: 31959642
Abstract
Prevailing dietary guidelines have widely recommended diets relatively low in red and processed meats and high in minimally processed plant foods for the prevention of chronic diseases. However, an ad hoc research group called the Nutritional Recommendations (NutriRECS) consortium recently issued "new dietary guidelines" encouraging individuals to continue their current meat consumption habits due to "low certainty" of the evidence, difficulty of altering meat eaters' habits and preferences, and the lack of need to consider environmental impacts of red meat consumption. These recommendations are not justified, in large part because of the flawed methodologies used to review and grade nutritional evidence. The evidence evaluation was largely based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria, which are primarily designed to grade the strength of evidence for clinical interventions especially pharmacotherapy. However, the infeasibility for conducting large, long-term randomized clinical trials on most dietary, lifestyle, and environmental exposures makes the criteria inappropriate in these areas. A separate research group proposed a modified and validated system for rating the meta-evidence on nutritional studies (NutriGRADE) to address several limitations of the GRADE criteria. Applying NutriGRADE, the evidence on the positive association between red and processed meats and type 2 diabetes was rated to be of "high quality," while the evidence on the association between red and processed meats and mortality was rated to be of "moderate quality." Another important limitation is that inadequate attention was paid to what might be replacing red meat, be it plant-based proteins, refined carbohydrates, or other foods. In summary, the red/processed meat recommendations by NutriRECS suffer from important methodological limitations and involve misinterpretations of nutritional evidence. To improve human and planetary health, dietary guidelines should continue to emphasize dietary patterns low in red and processed meats and high in minimally processed plant foods such as fruits and vegetables, whole grains, nuts, and legumes.

Effect of Sunscreen Application on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial.
Matta MK, Florian J, Zusterzeel R, Pilli NR, Patel V, Volpe DA, Yang Y, Oh L, Bashaw E, Zineh I, Sanabria C, Kemp S, Godfrey A, Adah S, Coelho S, Wang J, Furlong LA, Ganley C, Michele T, Strauss DG.
JAMA. 2020 Jan 21;323(3):256-267. doi: 10.1001/jama.2019.20747.
PMID: 31961417
Abstract
IMPORTANCE:
A prior pilot study demonstrated the systemic absorption of 4 sunscreen active ingredients; additional studies are needed to determine the systemic absorption of additional active ingredients and how quickly systemic exposure exceeds 0.5 ng/mL as recommended by the US Food and Drug Administration (FDA).
OBJECTIVE:
To assess the systemic absorption and pharmacokinetics of the 6 active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate) in 4 sunscreen products under single- and maximal-use conditions.
DESIGN, SETTING, AND PARTICIPANTS:
Randomized clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) was conducted in 48 healthy participants. The study was conducted between January and February 2019.
INTERVENTIONS:
Participants were randomized to 1 of 4 sunscreen products, formulated as lotion (n = 12), aerosol spray (n = 12), nonaerosol spray (n = 12), and pump spray (n = 12). Sunscreen product was applied at 2 mg/cm2 to 75% of body surface area at 0 hours on day 1 and 4 times on day 2 through day 4 at 2-hour intervals, and 34 blood samples were collected over 21 days from each participant.
MAIN OUTCOMES AND MEASURES:
The primary outcome was the maximum plasma concentration of avobenzone over days 1 through 21. Secondary outcomes were the maximum plasma concentrations of oxybenzone, octocrylene, homosalate, octisalate, and octinoxate over days 1 through 21.
RESULTS:
Among 48 randomized participants (mean [SD] age, 38.7 [13.2] years; 24 women [50%]; 23 white [48%], 23 African American [48%], 1 Asian [2%], and 1 of unknown race/ethnicity [2%]), 44 (92%) completed the trial. Geometric mean maximum plasma concentrations of all 6 active ingredients were greater than 0.5 ng/mL, and this threshold was surpassed on day 1 after a single application for all active ingredients. For avobenzone, the overall maximum plasma concentrations were 7.1 ng/mL (coefficient of variation [CV], 73.9%) for lotion, 3.5 ng/mL (CV, 70.9%) for aerosol spray, 3.5 ng/mL (CV, 73.0%) for nonaerosol spray, and 3.3 ng/mL (CV, 47.8%) for pump spray. For oxybenzone, the concentrations were 258.1 ng/mL (CV, 53.0%) for lotion and 180.1 ng/mL (CV, 57.3%) for aerosol spray. For octocrylene, the concentrations were 7.8 ng/mL (CV, 87.1%) for lotion, 6.6 ng/mL (CV, 78.1%) for aerosol spray, and 6.6 ng/mL (CV, 103.9%) for nonaerosol spray. For homosalate, concentrations were 23.1 ng/mL (CV, 68.0%) for aerosol spray, 17.9 ng/mL (CV, 61.7%) for nonaerosol spray, and 13.9 ng/mL (CV, 70.2%) for pump spray. For octisalate, concentrations were 5.1 ng/mL (CV, 81.6%) for aerosol spray, 5.8 ng/mL (CV, 77.4%) for nonaerosol spray, and 4.6 ng/mL (CV, 97.6%) for pump spray. For octinoxate, concentrations were 7.9 ng/mL (CV, 86.5%) for nonaerosol spray and 5.2 ng/mL (CV, 68.2%) for pump spray. The most common adverse event was rash, which developed in 14 participants.
CONCLUSIONS AND RELEVANCE:
In this study conducted in a clinical pharmacology unit and examining sunscreen application among healthy participants, all 6 of the tested active ingredients administered in 4 different sunscreen formulations were systemically absorbed and had plasma concentrations that surpassed the FDA threshold for potentially waiving some of the additional safety studies for sunscreens. These findings do not indicate that individuals should refrain from the use of sunscreen.

The Putative Caloric Restriction Mimetic Resveratrol has Moderate Impact on Insulin Sensitivity, Body Composition and the Metabolome in Mice.
Günther I, Rimbach G, Mack C, Weinert C, Danylec N, Lüersen K, Birringer M, Bracher F, Soukup ST, Kulling SE, Pallauf K.
Mol Nutr Food Res. 2020 Jan 21:e1901116. doi: 10.1002/mnfr.201901116. [Epub ahead of print]
PMID: 31962371
Abstract
SCOPE:
Data on resveratrol-(trans-3,5,4'-trihydroxystilbene)-induced caloric-restriction-(CR)-mimicking effects in mice receiving a high-fat diet (HFD) are contradictory. We hypothesized that this could possibly stem from different bioactivities of resveratrol (RSV) microbial metabolites.
METHODS AND RESULTS:
We fed C57BL/6Rj mice an ad-libitum HFD supplemented with RSV or its metabolites, dihydroresveratrol (DHR) and lunularin (LUN) (approximately 28 mg (dihydro)stilbene/kg mouse*day) and included a 40% CR group in our study. While the CR mice showed robust changes in bodyweight and composition, hormone levels and mRNA expression, we found slight changes (more muscle, less adipose tissue) in body composition, leptin and insulin levels in RSV-supplemented mice compared to the ad-libitum controls. LUN hardly and DHR did not change the hormone levels measured. Metabolome analysis of serum showed changes in CR mice but only slight, if any, changes in RSV-, DHR- or LUN-supplemented mice compared to the controls. Evaluating the capability of RSV and its metabolites to inhibit carbohydrate-hydrolyzing enzymes in vitro, we found that RSV reduced α-glucosidase activity to a stronger extent than DHR and LUN.
CONCLUSION:
Decelerated carbohydrate breakdown by RSV might have contributed to the moderate impact of dietary RSV supplementation on mouse insulin sensitivity (lowered fasting and post-glucose-bolus insulin levels).
KEYWORDS:
Dihydroresveratrol; gut metabolites; lunularin; metabolomics; α-glucosidase

Association of Low-Carbohydrate and Low-Fat Diets With Mortality Among US Adults.
Shan Z, Guo Y, Hu FB, Liu L, Qi Q.
JAMA Intern Med. 2020 Jan 21. doi: 10.1001/jamainternmed.2019.6980. [Epub ahead of print]
PMID: 31961383
https://sci-hub.tw/10.1001/jamainternmed.2019.6980
Abstract
IMPORTANCE:
It is crucial to incorporate quality and types of carbohydrate and fat when investigating the associations of low-fat and low-carbohydrate diets with mortality.
OBJECTIVE:
To investigate the associations of low-carbohydrate and low-fat diets with total and cause-specific mortality among US adults.
DESIGN, SETTING, AND PARTICIPANTS:
This prospective cohort study used data from the US National Health and Nutrition Examination Survey from 1999 to 2014 from 37 233 adults 20 years or older with 24-hour dietary recall data. Data were analyzed from July 5 to August 27, 2019.
EXPOSURES:
Overall, unhealthy, and healthy low-carbohydrate-diet and low-fat-diet scores based on the percentage of energy as total and subtypes of carbohydrate, fat, and protein.
MAIN OUTCOMES AND MEASURES:
All-cause mortality from baseline until December 31, 2015, linked to National Death Index mortality data.
RESULTS:
A total of 37 233 US adults (mean [SD] age, 49.7 [18.3] years; 19 598 [52.6%] female) were included in the present analysis. During 297 768 person-years of follow-up, 4866 total deaths occurred. Overall low-carbohydrate-diet and low-fat-diet scores were not associated with total mortality. The multivariable-adjusted hazard ratios for total mortality per 20-percentile increase in dietary scores were 1.07 (95% CI, 1.02-1.11; P = .01 for trend) for unhealthy low-carbohydrate-diet score, 0.91 (95% CI, 0.87-0.95; P < .001 for trend) for healthy low-carbohydrate-diet score, 1.06 (95% CI, 1.01-1.12; P = .04 for trend) for unhealthy low-fat-diet score, and 0.89 (95% CI, 0.85-0.93; P < .001 for trend) for healthy low-fat-diet score. The associations remained similar in the stratification and sensitivity analyses.
CONCLUSIONS AND RELEVANCE:
In this study, overall low-carbohydrate-diet and low-fat-diet scores were not associated with total mortality. Unhealthy low-carbohydrate-diet and low-fat-diet scores were associated with higher total mortality, whereas healthy low-carbohydrate-diet and low-fat-diet scores were associated with lower total mortality. These findings suggest that the associations of low-carbohydrate and low-fat diets with mortality may depend on the quality and food sources of macronutrients.

Edited January 25, 2020 by AlPater

[AlPater]

Psychosocial work stressors and risk of mortality in Australia: analysis of data from the Household, Income and Labour Dynamics in Australia survey.
Taouk Y, LaMontagne AD, Spittal MJ, Milner A.
Occup Environ Med. 2020 Jan 23. pii: oemed-2019-106001. doi: 10.1136/oemed-2019-106001. [Epub ahead of print]
PMID: 31974285
Abstract
OBJECTIVE:
To examine the association between exposures to psychosocial work stressors and mortality in a nationally representative Australian working population sample.
METHODS:
18 000 participants from the Household, Income and Labour Dynamics in Australia survey with self-reported job demands, job control, job security and fair pay psychosocial work stressors exposures at baseline were followed for up to 15 waves. Cox proportional hazards regression models were used to examine the association between psychosocial work stressors and mortality. Models were serially adjusted for each subgroup of demographic, socioeconomic, health and behavioural risk factors.
RESULTS:
Low job control was associated with a 39% increase in the risk of all-cause mortality (HR 1.39; 95% CI 1.04 to 1.85), controlling for demographic, socioeconomic, health and behavioural factors. A decreased risk of mortality was observed for workers with exposure to high job demands (HR 0.76; 95% CI 0.60 to 0.96, adjusted for gender and calendar), but the risk was attenuated after serially adjusting for socioeconomic status, health (HR=0.84; 95% CI 0.65 to 1.08) and behavioural (HR=0.79; 95% CI 0.60 to 1.04) factors. There did not appear to be an association between exposure to job insecurity (HR 1.03; 95% CI 0.79 to 1.33) and mortality, or unfair pay and mortality (HR 1.04; 95% CI 0.80 to 1.34).
CONCLUSIONS:
Low job control may be associated with an increased risk of all-cause mortality. Policy and practice interventions that reduce the adverse impact of low job control in stressful work environments could be considered to improve health and decrease risk of mortality.
KEYWORDS:
epidemiology; longitudinal studies; mortality studies; statistics; workload

Trends in alcohol consumption in relation to cause-specific and all-cause mortality in the United States: a report from the NHANES linked to the US mortality registry.
Ricci C, Schutte AE, Schutte R, Smuts CM, Pieters M.
Am J Clin Nutr. 2020 Jan 24. pii: nqaa008. doi: 10.1093/ajcn/nqaa008. [Epub ahead of print]
PMID: 31978218
Abstract
BACKGROUND:
Excessive alcohol use is the third leading cause of mortality in the United States, where alcohol use consistently increased over the last decades. This trend is currently maintained, despite regulatory policies aimed to counteract it. While the increased health risks resulting from alcohol use are evident, some open questions regarding alcohol use and its consequences in the US population remain.

OBJECTIVES:
The current work aims to evaluate the relation between alcohol consumption trends over a period of 15 y with all-cause and cause-specific mortality. In addition, we evaluate the adequacy of the current alcohol recommended limits according to the 2015-2020 US Dietary Guidelines for Americans (USDGA).
METHODS:
This was a prospective population-based study defined by the NHANES conducted over the period 1999-2014 linked to US mortality registry in 2015.
RESULTS:
The sample, composed of 34,672 participants, was observed for a median period of 7.8 y, totaling 282,855 person-years. In the present sample, 4,303 deaths were observed. Alcohol use increased during the period 1999-2014. Alcohol use above the current US recommendations was associated with increased all-cause and cause-specific mortality risk, ranging from 39% to 126%. A proportion of these deaths, ranging from 19% to 26%, could be theoretically prevented if US citizens followed current guidelines, and 13% of all-cause deaths in men could be avoided if the current US guidelines for women (1 standard drink/d) were applied to them.
CONCLUSIONS:
The present study provides evidence in support of limiting alcohol intake in adherence to the USDGA recommendations.
KEYWORDS:
NHANES; US guidelines; alcohol use; alcohol use trend; mortality

Short-term time-restricted feeding is safe and feasible in non-obese healthy midlife and older adults.
Martens CR, Rossman MJ, Mazzo MR, Jankowski LR, Nagy EE, Denman BA, Richey JJ, Johnson SA, Ziemba BP, Wang Y, Peterson CM, Chonchol M, Seals DR.
Geroscience. 2020 Jan 23. doi: 10.1007/s11357-020-00156-6. [Epub ahead of print]
PMID: 31975053
https://sci-hub.tw/10.1007/s11357-020-00156-6
Abstract
Chronic calorie restriction (CR) improves cardiovascular function and several other physiological markers of healthspan. However, CR is impractical in non-obese older humans due to potential loss of lean mass and bone density, poor adherence, and risk of malnutrition. Time-restricted feeding (TRF), which limits the daily feeding period without requiring a reduction in calorie intake, may be a promising alternative healthspan-extending strategy for midlife and older adults; however, there is limited evidence for its feasibility and efficacy in humans. We conducted a randomized, controlled pilot study to assess the safety, tolerability, and overall feasibility of short-term TRF (eating <8 h day-1 for 6 weeks) without weight loss in healthy non-obese midlife and older adults, while gaining initial insight into potential efficacy for improving cardiovascular function and other indicators of healthspan. TRF was safe and well-tolerated, associated with excellent adherence and reduced hunger, and did not influence lean mass, bone density, or nutrient intake. Cardiovascular function was not enhanced by short-term TRF in this healthy cohort, but functional (endurance) capacity and glucose tolerance were modestly improved. These results provide a foundation for conducting larger clinical studies of TRF in midlife and older adults, including trials with a longer treatment duration.
KEYWORDS:
Aging; Calorie restriction; Healthspan; Intermittent fasting

[AlPater]

Benefits of pulse consumption on metabolism and health: A systematic review of randomized controlled trials.
Ferreira H, Vasconcelos M, Gil AM, Pinto E.
Crit Rev Food Sci Nutr. 2020 Jan 25:1-12. doi: 10.1080/10408398.2020.1716680. [Epub ahead of print]
PMID: 31983216
https://sci-hub.tw/10.1080/10408398.2020.1716680
Abstract
Pulses are nutrient-dense foods that have for a long time been empirically known to have beneficial effects in human health. In the last decade, several studies have gathered evidence of the metabolic benefits of pulse intake. However, it remains unclear at what amounts these effects may be attained. This study aimed to systematically review the scientific outputs of the last two decades regarding health benefits of pulse consumption and the amounts necessary for positive outcomes to be achieved. A PubMed search including keywords [("dietary pulses", "pulses", "legumes", "grain legumes", "bean", "chickpea", "pea", "lentil", "cowpea", "faba bean", "lupin") and ("inflammation", "inflammatory markers", "C-reactive protein", "blood lipids", "cholesterol", "cardiometabolic health", "cardiovascular disease", "diabetes", "glycaemia", "insulin", "HOMA-IR", "body weight", "body fat", "obesity", "overweight", "metabolome", "metabolic profile", "metabolomics", "biomarkers", "microbiome", "microbiota", "gut")] was performed. Only English written papers referring to human dietary interventions, longer than one day, focusing on whole pulses intake, were included. Most of the twenty eligible publications reported improvements in blood lipid profile, blood pressure, inflammation biomarkers, as well as, in body composition, resulting from pulse daily amounts of 150 g (minimum-maximum: 54-360 g/day; cooked). Concerns regarding methodological approaches are evident and the biochemical mechanisms underlying such effects require further investigation.
KEYWORDS:
Biomarkers; cardiovascular risk factors; ingestion; legume grains; well-being

Association between adiposity measures and COPD risk in Chinese adults.
Li J, Zhu L, Wei Y, Lv J, Guo Y, Bian Z, Du H, Yang L, Chen Y, Zhou Y, Gao R, Chen J, Chen Z, Cao W, Yu C, Li L; China Kadoorie Biobank Collaborative Group.
Eur Respir J. 2020 Jan 24. pii: 1901899. doi: 10.1183/13993003.01899-2019. [Epub ahead of print]
PMID: 31980495
Abstract
Bodyweight and fat distribution may be related to Chronic obstructive pulmonary disease (COPD) risk. Limited prospective evidence linked COPD to abdominal adiposity. We investigated the association of body mass index (BMI) and measures of abdominal adiposity with COPD risk in a prospective cohort study.The China Kadoorie Biobank (CKB) recruited participants aged 30-79 years from ten areas across China. Anthropometric indexes were objectively measured at the baseline survey during 2004-2008. After exclusion of participants with prevalent COPD and major chronic diseases, 452 259 participants were included and followed up through the end of 2016. We used Cox models to estimate adjusted hazard ratios relating adiposity to risk of COPD hospitalisation or death.Over an average of 10.1-year follow-up, 10 739 COPD hospitalisation events and deaths were reported. Compared with normal BMI (BMI 18.5 to <24.0 kg·m-2), underweight (BMI<18.5 kg·m-2) individuals had increased risk of COPD, with adjusted HR (95% CI) to be 1.78 (1.66-1.89). Overweight (BMI 24.0 to <28.0 kg·m-2) and obesity (BMI≥28.0 kg·m-2) were not associated with an increased risk after adjustment for waist circumference. A higher waist circumference (≥85 cm for men and ≥80 cm for women) was positively associated with COPD risk after adjustment for BMI. Waist-to-hip ratio and waist-to-height ratio were also positively related to COPD risk.Abdominal adiposity and underweight were risk factors for COPD in Chinese adults. Both BMI and measures of Abdominal adiposity should be considered in the prevention of COPD.
 

[AlPater]

Psychological distress and mortality among US adults: prospective cohort study of 330 367 individuals.
Yang L, Zhao M, Magnussen CG, Veeranki SP, Xi B.
J Epidemiol Community Health. 2020 Jan 28. pii: jech-2019-213144. doi: 10.1136/jech-2019-213144. [Epub ahead of print]
PMID: 31992611
http://www.midss.org/sites/default/files/k6_self_admin_updated_08-08-11.pdf
Abstract
BACKGROUND:
Previous studies have shown inconsistent findings on the association between psychological distress and risk of mortality. This study aimed to address this inconsistent association using a large US population-based cohort.
METHODS:
This study used data from 1997 to 2009 US National Health Interview Survey, which were linked with National Death Index through 31 December 2011. Psychological distress was measured using Kessler-6 scale and was categorised into six groups based on scores as 0, 1-3, 4-6, 7-9, 10-12 and ≥13. Main outcomes were all-cause, cancer-specific and cardiovascular disease (CVD)-specific mortality. Analyses were completed in 2019. Cox proportional hazards models were used to determine the association between psychological distress and mortality.
RESULTS:
A total of 330 367 participants aged ≥18 years were included. During a mean follow-up of 8.2 years, 34 074 deaths occurred, including 8320 cancer-related and 8762 CVD-related deaths. There was a dose-response association between psychological distress and all-cause mortality. Compared with the 0 score category, adjusted HRs (95% CIs) for other categorical psychological distress scores, that is, 1-3, 4-6, 7-9, 10-12 and ≥13, were 1.09 (1.05 to 1.12), 1.22 (1.17 to 1.27), 1.38 (1.31 to 1.46), 1.49 (1.40 to 1.59) and 1.57 (1.47 to 1.68), respectively. Corresponding values for cancer-specific mortality were 1.06 (0.99 to 1.12), 1.13 (1.04 to 1.23), 1.27 (1.14 to 1.42), 1.38 (1.22 to 1.57) and 1.32 (1.15 to 1.51), respectively; those for CVD-specific mortality were 1.11 (1.05 to 1.18), 1.22 (1.12 to 1.32), 1.30 (1.17 to 1.45), 1.38 (1.20 to 1.58), and 1.46 (1.27 to 1.68), respectively.
CONCLUSIONS:
We found a dose-response relationship between psychological distress and all-cause and cause-specific mortality, emphasising the need for early prevention strategies among individuals with potential psychological distress.

The Effects of Different Feeding Routines on Welfare in Laboratory Mice.
Feige-Diller J, Krakenberg V, Bierbaum L, Seifert L, Palme R, Kaiser S, Sachser N, Richter SH.
Front Vet Sci. 2020 Jan 14;6:479. doi: 10.3389/fvets.2019.00479. eCollection 2019.
PMID: 31993444
Abstract
The accepted norm in most laboratories around the globe is feeding laboratory mice an ad libitum diet, although several health impairments are well-established. In contrast, reducing the animals' body weight by feeding them less food once per day (referred to as 24 h schedule) has been shown to enhance life span and reduce disease susceptibility. Against this background, this study aimed at systematically investigating the effects of different feeding routines. Therefore, three feeding routines were compared to the standard ad libitum feeding and effects on body weight development and welfare were investigated in male C57BL/6J mice. In particular, a 24 h schedule group, an AUTO group, characterized by an automated supply of small pieces of food all over the day, and a 4 h removal group, characterized by daily removal of food for 4 h, were studied. While the removal of food for 4 h per day did not lead to a reduction of body weight, and hence is unlikely to prevent negative effects of overfeeding, both the 24 h schedule group and the AUTO group led to the aspired body weight reduction. In the AUTO group, however, higher levels of corticosterone metabolites and stereotypies were observed, implying a rather negative impact on welfare. By contrast, no distinct negative effects of a 24 h schedule were found. Studies like this underline the general need for evidence-based severity assessments of any procedure involving living animals.
KEYWORDS:
anxiety-like behavior; body weight; corticosterone metabolites; feeding routines; laboratory mice; welfare

Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials.
Keum N, Lee DH, Greenwood DC, Manson JE, Giovannucci E.
Ann Oncol. 2019 May;30(5):733-743. doi: 10.1093/annonc/mdz059. Epub 2019 Dec 4. Review.
PMID: 31987340
Abstract
BACKGROUND:
Previous meta-analyses of randomized controlled trials (RCTs) of vitamin D supplementation and total cancer incidence and mortality found inconsistent results, and most included trials administered generally low doses of vitamin D (≤1100IU/day). We updated the meta-analysis by incorporating recent RCTs that have tested higher doses of vitamin D supplements.
MATERIALS AND METHODS:
PubMed and Embase were searched from the inception to November 2018. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a random-effects model.
RESULTS:
For total cancer incidence, 10 trials were included [6537 cases; 3-10years of follow-up; 54-135nmol/l of attained levels of circulating 25(OH) vitamin D [25(OH)D] in the intervention group]. The summary RR was 0.98 (95% CI, 0.93-1.03; P = 0.42; I2 = 0%). The results remained null across subgroups tested, including even when attained 25(OH)D levels exceeded 100nmol/l (RR, 0.95; 95% CI, 0.83-1.09; P = 0.48; I2 = 26%). For total cancer mortality, five trials were included [1591 deaths; 3-10years of follow-up; 54-135nmol/l of attained levels of circulating 25(OH)D in the intervention group]. The summary RR was 0.87 (95% CI, 0.79-0.96; P = 0.005; I2 = 0%), which was largely attributable to interventions with daily dosing (as opposed to infrequent bolus dosing). No statistically significant heterogeneity was observed by attained levels of circulating 25(OH)D (Pheterogeneity = 0.83), with RR being 0.88 (95% CI, 0.78-0.98; P = 0.02; I2 = 0%) for ≤100nmol/l and 0.85 (95% CI, 0.70-1.03; P = 0.11; I2 = 0%) for >100nmol/l.
CONCLUSIONS:
In an updated meta-analysis of RCTs, vitamin D supplementation significantly reduced total cancer mortality but did not reduce total cancer incidence.
KEYWORDS:
cancer incidence; cancer mortality; circulating 25(OH)D; meta-analysis; randomized controlled trial; vitamin D supplements

Dietary fiber intake and total and cause-specific mortality: the Japan Public Health Center-based prospective study.
Katagiri R, Goto A, Sawada N, Yamaji T, Iwasaki M, Noda M, Iso H, Tsugane S.
Am J Clin Nutr. 2020 Jan 28. pii: nqaa002. doi: 10.1093/ajcn/nqaa002. [Epub ahead of print]
PMID: 31990973
Abstract
BACKGROUND:
An inverse association has been shown between dietary fiber intake and several noncommunicable diseases. However, evidence of this effect remains unclear in the Asian population.
OBJECTIVE:
We examined the association between dietary fiber intake and all-cause and cause-specific mortality, as well as the association between fiber intake from dietary sources and all-cause mortality.
METHODS:
We conducted a large-scale population-based cohort study (Japan Public Health Center-based prospective study). A validated questionnaire with 138 food items was completed by 92,924 participants (42,754 men and 50,170 women) aged 45-74 y. Dietary fiber intake was calculated and divided into quintiles. HR and 95% CI of total and cause-specific mortality were reported.
RESULTS:
During the mean follow-up of 16.8 y, 19,400 deaths were identified. In multivariable adjusted models, total, soluble, and insoluble fiber intakes were inversely associated with all-cause mortality. The HRs of total mortality in the highest quintile of total fiber intake compared with the lowest quintile were 0.77 (95% CI: 0.72, 0.82; Ptrend <0.0001) in men and 0.82 (95% CI: 0.76, 0.89; Ptrend <0.0001) in women. Increased quintiles of dietary fiber intake were significantly associated with decreased mortality due to total cardiovascular disease (CVD), respiratory disease, and injury in both men and women, whereas dietary fiber intake was inversely associated with cancer mortality in men but not women. Fiber from fruits, beans, and vegetables, but not from cereals, was inversely associated with total mortality.
CONCLUSION:
In this large-scale prospective study with a long follow-up period, dietary fiber was inversely associated with all-cause mortality. Since intakes of dietary fiber, mainly from fruits, vegetables, and beans were associated with lower all-cause mortality, these food sources may be good options for people aiming to consume more fiber.
KEYWORDS:
Asian population; beans; cohort study; dietary fiber intake; food source; fruits and vegetables; mortality; noncommunicable disease

[AlPater]

Metabolic and Immunological Effects of Intermittent Fasting on a Ketogenic Diet Containing Medium-Chain Triglycerides in Healthy Dogs.
Leung YB, Cave NJ, Heiser A, Edwards PJB, Godfrey AJR, Wester T.
Front Vet Sci. 2020 Jan 8;6:480. doi: 10.3389/fvets.2019.00480. eCollection 2019.
PMID: 31998762
Abstract
In several species, intermittent fasting (IF) has been shown to have beneficial effects, including delayed aging, increased lifespan, increased insulin sensitivity, reduced ischemic tissue damage, delayed onset of neurodegenerative disease and improved neuronal repair following injury. However, the metabolic and immunological effects of IF have not been well-established in dogs. The aim of this study was to examine the effects of a 48 h IF regimen using a low fat and a high fat diet in healthy dogs by quantifying the metabolic, hormonal, and immunological changes. We hypothesized that IF dogs would have higher blood ketone and ghrelin concentrations, lower blood leptin, insulin and glucose concentrations, and signs of immunosuppression compared to dogs eating daily. Ten healthy adult dogs were randomized into three group and underwent three feeding regimes in a 3 × 3 Latin square design: twice a day feeding on a low fat (23% energy from fat; LF) diet, 48 h fasting on a low fat diet, and 48 h fasting on a high fat enriched with medium-chain triglycerides (68% energy from fat; HF) diet. Body weight, food intake, activity, blood glucose, β-hydroxybutyrate, leptin, ghrelin, and insulin were measured. Lymphocyte proliferation and neutrophil/macrophage phagocytosis and respiratory burst were measured as markers of immune function. Nuclear magnetic resonance spectroscopy was used to relatively quantify plasma metabolites. When the dogs were IF on a HF diet, they had the highest concentration of blood ketones (mean 0.061 mmol/L, SD 0.024), whereas they had the lowest concentration (mean 0.018 mmol/L, SD 0.004) when fed daily. Blood glucose and insulin concentrations were lower in IF dogs on a HF diet compared to daily feeding or IF on a LF diet. There was an increase in plasma β-hydroxybutyrate concentrations, and a reduction in glucose and insulin concentrations when dogs were IF on a HF diet. There was only a decline in the immune parameters studied when the dogs were IF on a LF diet, which was not seen when on the HF diet. The results of this study indicate the potential of IF to be further investigated as a potential beneficial feeding regime for dogs.
KEYWORDS:
beta-hydroxybutyrate; diet; dog; fasting; immunity; ketogenic; ketone; medium-chain

Lycopene and bone: an in vitro investigation and a pilot prospective clinical study.
Russo C, Ferro Y, Maurotti S, Salvati MA, Mazza E, Pujia R, Terracciano R, Maggisano G, Mare R, Giannini S, Romeo S, Pujia A, Montalcini T.
J Transl Med. 2020 Jan 29;18(1):43. doi: 10.1186/s12967-020-02238-7.
PMID: 31996227
https://translational-medicine.biomedcentral.com/track/pdf/10.1186/s12967-020-02238-7
Abstract
BACKGROUND:
There are several effective therapies for osteoporosis but these agents might cause serious adverse events. Lycopene intake could prevent bone loss, however studies on its effects on bone are scarce. Our aim was to investigate the effects of lycopene on osteoblast cells as well as bone mineral density and bone turnover markers in postmenopausal women.
METHODS:
We investigated the effect of lycopene on the Wnt/β-catenin and ERK 1/2 pathways, RUNX2, alkaline phosphatase, RANKL and COL1A of Saos-2. We also carried out a pilot controlled clinical study to verify the feasibility of an approach for bone loss prevention through the intake of a lycopene-rich tomato sauce in 39 postmenopausal women.
RESULTS:
Lycopene 10 µM resulted in higher β-catenin and phERK1/2 protein Vs the vehicle (p = 0.04 and p = 0.006). RUNX2 and COL1A mRNA was induced by both 5 and 10 µM doses (p = 0.03; p = 0.03 and p = 0.03; p = 0.05) while RANKL mRNA was reduced (p < 0.05). A significant bone density loss was not detected in women taking the tomato sauce while the control group had bone loss (p = 0.002). Tomato sauce intake resulted in a greater bone alkaline phosphatase reduction than the control (18% vs 8.5%, p = 0.03).
CONCLUSIONS:
Lycopene activates the WNT/β-catenin and ERK1/2 pathways, upregulates RUNX2, alkaline phosphatase, COL1A and downregulates RANKL Saos-2. These processes contributed to prevent bone loss in postmenopausal women.
KEYWORDS:
Bone metabolism; Bone mineral density; Lycopene; Nutraceutical; Osteoporosis

Insulin-like growth factor-1, insulin-like growth factor binding protein-3 and the incidence of malignant neoplasms in a nested case-control study.
Adachi Y, Nojima M, Mori M, Himori R, Kubo T, Yamano HO, Lin Y, Wakai K, Tamakoshi A.
Cancer Prev Res (Phila). 2020 Jan 29. pii: canprevres.0375.2019. doi: 10.1158/1940-6207.CAPR-19-0375. [Epub ahead of print]
PMID: 31996369
Abstract
Insulin-like growth factor (IGF)-1 is a potent mitogen, but IGF binding protein (IGFBP)-3 inhibits IGF1. To elucidate the relationship between both (IGF)-1 and IGFBP and the risk of tumorigenesis, the association between IGF1 and IGFBP3 serum levels and of malignant tumor incidence was investigated in a prospective case-control study nested in the Japan Collaborative Cohort (JACC) Study. A baseline survey was started in 1988-1990, 110,585 subjects were enrolled, and 35% of participants donated blood samples. Those who had been diagnosed with malignant tumors by 1997 were considered cases. The analysis involved 1,349 cases and 4,012 controls. Conditional logistic regression was used to estimate odds ratios (ORs) for cancer incidence associated with IGF-related molecules. After controlling for alcohol intake, BMI, and smoking, participants with high total-IGFBP3 and free-IGFBP3, which is estimated by the molar difference of (IGFBP3 - IGF1), had a risk of future neoplasms (p for trend= 0.014 and 0.009, respectively), but those with IGF1 did not. People in the second to fifth quintiles had a lower risk than those in the first quintile (ORs 0.676-0.736 and 0.657-0.870, respectively). Limiting subjects to those followed for 3 years weakened the negative associations of total- and free-IGFBP3, whereas a positive relationship of free-IGF1, which was estimated by the molar ratio of IGF1/IGFBP3, was seen (p for trend= 0.0016, 0.012, and 0.013, respectively). After controlling for alcohol intake, smoking, BMI, and diabetes mellitus, the results were confirmed. These findings suggest that serum IGF1 and IGFBP3 are related to future risk of malignant neoplasms.

Association of soy and fermented soy product intake with total and cause specific mortality: prospective cohort study.
Katagiri R, Sawada N, Goto A, Yamaji T, Iwasaki M, Noda M, Iso H, Tsugane S; Japan Public Health Center-based Prospective Study Group.
BMJ. 2020 Jan 29;368:m34. doi: 10.1136/bmj.m34.
PMID: 31996350
https://www.bmj.com/content/bmj/368/bmj.m34.full.pdf
Abstract
OBJECTIVE:
To investigate the association between several types of soy products and all cause and cause specific mortality.
DESIGN:
Population based cohort study.
SETTING:
Japan Public Health Centre-based Prospective Study, which includes 11 public health centre areas in Japan.
PARTICIPANTS:
92 915 participants (42 750 men and 50 165 women) aged 45 to 74 years.
EXPOSURES:
Intake of total soy products, fermented soy products (natto and miso), non-fermented soy products, and tofu from a five year survey questionnaire.
MAIN OUTCOME MEASURES:
All cause and cause specific mortality (cancer, total cardiovascular disease, heart disease, cerebrovascular disease, respiratory disease, and injury) obtained from residential registries and death certificates.
RESULTS:
During 14.8 years of follow-up, 13 303 deaths were identified. In the multivariable adjusted models, intake of total soy products was not significantly associated with total mortality. Compared with the lowest fifth of total soy product intake, the hazard ratios in the highest fifth were 0.98 (95% confidence interval 0.91 to 1.06, Ptrend=0.43) in men and 0.98 (0.89 to 1.08, Ptrend=0.46) in women. Intake of fermented soy products was inversely associated with all cause mortality in both sexes (highest versus lowest fifth: 0.90 (0.83 to 0.97), Ptrend=0.05 in men, and 0.89 (0.80 to 0.98), Ptrend=0.01 in women). Natto showed significant and inverse associations with total cardiovascular disease related mortality in both sexes.
CONCLUSIONS:
In this study a higher intake of fermented soy was associated with a lower risk of mortality. A significant association between intake of total soy products and all cause mortality was not, however, observed. The findings should be interpreted with caution because the significant association of fermented soy products might be attenuated by unadjusted residual confounding.

[AlPater]

Cardiorespiratory Fitness Is Associated with Early Death Among Healthy Young and Middle-aged Baby Boomers and Generation Xers.
Cao C, Yang L, Cade WT, Racette SB, Park Y, Cao Y, Friedenreich CM, Hamer M, Stamatakis E, Smith L.
Am J Med. 2020 Jan 29. pii: S0002-9343(20)30054-1. doi: 10.1016/j.amjmed.2019.12.041. [Epub ahead of print]
PMID: 32006474
Abstract
BACKGROUND:
Increased mortality associated with low cardiorespiratory fitness has shown to take effect during late adulthood in previous generations. A recent rise in early death was observed in the US. We investigated the impact of low cardiorespiratory fitness during young and middle adulthood on premature death in healthy adults from recent generations.
METHODS:
A prospective cohort study of a nationally representative sample of US Baby Boomers and Generation Xers (born 1945-1980). Between 1999-2004, 3242 adults aged 20 to 49 years (weighted N=59 888 450; mean age, 33.8 ± 0.2 years) underwent submaximal treadmill exercise test in the National Health and Nutrition Examination Survey study. Weighted Cox proportional hazards regression were used to evaluate the association of cardiorespiratory fitness with premature death at 65 years or younger RESULTS: During a mean follow-up of 13.8 years, 104 deaths (weighted deaths N =1 326 808) occurred. Low cardiorespiratory fitness was associated with an increased risk of premature death due to all-cause (Hazard ratio , low vs. high: 2.26; 95% CI, 1.10 to 4.64, p for trend=.036) and cancer mortality (HR: low vs. moderate/high: 6.53; 95% CI, 2.38 to 17.9). Further, this association was stronger in adults aged 35 to 49 years at baseline (HR, 4.17 [95% CI, 1.19 to 9.11]).

CONCLUSION:
We observed an inverse association between cardiorespiratory fitness during middle adulthood and premature death, which was not detected in proceeding generations. These findings suggested that low cardiorespiratory fitness might be emerging to a new risk factor for early death among US Baby Boomers and Generation Xers.
KEYWORDS:
Baby Boomers; Cardiorespiratory fitness; Generation Xers; early death; middle-aged adults; young adults

The risk of urinary tract infection in vegetarians and non-vegetarians: a prospective study.
Chen YC, Chang CC, Chiu THT, Lin MN, Lin CL.
Sci Rep. 2020 Jan 30;10(1):906. doi: 10.1038/s41598-020-58006-6.
PMID: 32001729
Abstract
Urinary tract infection (UTI) is caused principally by ascending Escherichia coli infection via an intestine-stool-urethra route. Recent studies found that the strains of E. coli causing UTIs, called extra-intestinal pathogenic E. coli (ExPEC), were distinct from the intestinal pathogenic strains and normal commensal strains. Further analysis found the meat including poultry and pork is the major reservoir for ExPECs. Vegetarians avoid meat and should theoretically have less exposure to ExPEC. However, no study thus far has examined whether vegetarian diets reduce the risk of UTI. Our aim was to examine the association between vegetarian diet and UTI risk in a Taiwanese Buddhist population. We prospectively followed 9724 Buddhists free of UTI from 2005 to 2014. During the 10-year follow-up, 661 incident UTI cases were confirmed. Diet was assessed through a food frequency questionnaire. Cox regression was used to evaluate the prospective association between a vegetarian diet on risk of UTI while adjusting for age, sex, educational level, alcohol-drinking, smoking, hypertension, diabetes mellitus, hyperlipidemia, and disease conditions predisposing to UTIs. Overall, vegetarian diet was associated with 16% lower hazards (hazard ratio

---

: 0.84, 95% confidence interval [CI]: 0.71-0.99). In subgroup analysis, the protective association between vegetarian diet and UTI is observed mainly in the female (HR: 0.82, 95% CI: 0.69-0.99), never smokers (HR: 0.80, 95% CI: 0.67-0.95), and for uncomplicated UTI (HR: 0.81, 95% CI: 0.68-0.98).

The alternate-day fasting diet is a more effective approach than a calorie restriction diet on weight loss and hs-CRP levels.
Razavi R, Parvaresh A, Abbasi B, Yaghoobloo K, Hassanzadeh A, Mohammadifard N, Clark CCT, Morteza Safavi S.
Int J Vitam Nutr Res. 2020 Jan 31:1-9. doi: 10.1024/0300-9831/a000623. [Epub ahead of print]
PMID: 32003649
Abstract
Background and Objective: The aim of present study was to compare, and determine, the effects of a modified alternate-day fasting diet vs. calorie restriction on inflammatory indices and coagulation factors. Methods: This was a randomized clinical trial consisting of 80 metabolic syndrome patients, who were enrolled and randomly dichotomized into a modified alternate-day fasting diet or calorie restriction group for 4 months. We measured weight, body mass index (BMI), waist circumstance (WC), waist-hip-ratio (WHR) and fat mass as primary outcomes and assessed high sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and coagulation factors levels as secondary outcomes before and after intervention. Results: Compared to the calorie restriction diet, following a modified alternate-day fasting diet led to a greater reduction in body weight (kg) (-6.43 ± 4.34 vs -4.11 ± 4.27; P = 0.02), BMI (kg/m2) (-3.19 ± 2.90 vs -1.43 ± 2.72; P = 0.01), fat mass (kg) (-4.88 ± 2.09 vs -3.72 ± 2.43; P = 0.03), WC (cm) (-5.57 ± 5.64 vs -2.32 ± 5.95; P = 0.01) and WHR (-0.05 ± 0.06 vs -0.02 ± 0.07; P = 0.04). Furthermore, a greater change was found in hs-CRP levels (mg/L) (-2.06 ± 1.18 vs -0.97 ± 0.82; P = 0.03), prothrombin time (s) (1.41 ± 2.34 vs -0.41 ± 2.17; P < 0.001), activated partial thromboplastin time (s) (0.26 ± 3.70 vs -1.78 ± 3.56; P = 0.04) in modified alternate-day fasting diet when compared to calorie restriction diet. However, there was no difference in TNF-α or IL-6 and fibrinogen between groups (P > 0.05). Conclusions: These findings suggest that a modified alternate-day fasting diet can be a beneficial alternative for the management of body weight, fat mass and WC as well as hs-CRP and coagulation factors levels among metabolic syndrome patients.
KEYWORDS:
Alternate-day fasting diet; energy restriction; inflammation; metabolic syndrome

Edited February 2, 2020 by AlPater

[AlPater]

Association of trajectory of body mass index with knee pain risk in Japanese middle-aged women in a prospective cohort study: the Japan Nurses' Health Study.
Ito A, Hayashi K, Suzuki S, Ideno Y, Kurabayashi T, Ogata T, Seichi A, Akai M, Iwaya T.
BMJ Open. 2020 Feb 6;10(2):e033853. doi: 10.1136/bmjopen-2019-033853.
PMID: 32034025 Free Article
Abstract
OBJECTIVES:
To investigate whether body mass index (BMI) trajectory, lifestyle and reproductive factors are associated with knee pain risk among middle-aged women.
DESIGN:
Prospective study of the Japan Nurses' Health Study (JNHS).
SETTING:
The JNHS investigates the health of female nurses in Japan. Biennial follow-up questionnaires are mailed to the participants.
PARTICIPANTS:
The 7434 women aged over 40 years who responded to the 10-year self-administered follow-up questionnaire.
PRIMARY OUTCOME MEASURE:
Self-reported knee pain at the 10-year follow-up was the primary outcome. We analysed BMI (normal or overweight) trajectory data from a baseline survey to the 10-year follow-up survey using group-based trajectory modelling. Exposure measurements were BMI trajectory, BMI at age 18 years, lifestyle variables and reproductive history.
RESULTS:
BMI trajectories from baseline to the 10-year follow-up were divided into four groups: remained normal, remained overweight, gained weight or lost weight. At the 10-year follow-up, 1281 women (17.2%) reported knee pain. Multivariable logistic regression analysis revealed that compared with the remained normal group, multivariable-adjusted ORs (95% CI) of knee pain were 1.93 (1.60 to 2.33) for the remained overweight group, 1.60 (1.23 to 2.08) for the gained weight group and 1.40 (0.88 to 2.21) for the lost weight group. The attributable risk percent (95% CI) of the remained overweight group was 48.1% (37.3% to 57.0%) compared with the reference group of remained normal. Alcohol intake at baseline was significantly associated with knee pain.
CONCLUSIONS:
The lost weight group had a lower risk than the remained overweight group and the gained weight group and did not carry statistically significant risks for knee pain. Weight reduction and maintaining a normal BMI in middle age was important for preventing knee pain in women.
KEYWORDS:
epidemiology; knee; musculoskeletal disorders; public health

Dietary Nonheme, Heme, and Total Iron Intake and the Risk of Diabetes in Adults: Results From the China Health and Nutrition Survey.
He J, Fang A, Yu S, Shen X, Li K.
Diabetes Care. 2020 Feb 7. pii: dc192202. doi: 10.2337/dc19-2202. [Epub ahead of print]
PMID: 32033991
Abstract
OBJECTIVE:
Excessive iron intake has been linked to diabetes risk. However, the evidence is inconsistent. This study examined the association between dietary heme and nonheme iron intake and diabetes risk in the Chinese population.
RESEARCH DESIGN AND METHODS:
We included 17,026 adults (8,346 men and 8,680 women) who were part of the China Health and Nutrition Survey (1991-2015) prospective cohort. Dietary intake was measured by three consecutive 24-h dietary recalls combined with a household food inventory. Diabetes cases were identified through a questionnaire. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs.
RESULTS:
A total of 547 men and 577 women developed diabetes during 202,138 person-years of follow-up. For men, the adjusted HRs (95% CIs) for quintiles of nonheme iron intake were 1.00, 0.77 (0.58-1.02), 0.72 (0.54-0.97), 0.63 (0.46-0.85), and 0.87 (0.64-1.19) (P-nonlinearity = 0.0015). The corresponding HRs (95% CIs) for women were 1.00, 0.63 (0.48-0.84), 0.57 (0.43-0.76), 0.58 (0.43-0.77), and 0.67 (0.49-0.91) (P-nonlinearity < 0.0001). The dose-response curves for the association between nonheme iron and total iron intake and diabetes followed a reverse J shape in men and an L shape in women. No significant associations were observed between heme iron intake and diabetes risk.
CONCLUSIONS:
Total iron and nonheme iron intake was associated with diabetes risk, following a reverse J-shaped curve in men and an L-shaped curve in women. Sufficient intake of nonheme or total iron might be protective against diabetes, while excessive iron intake might increase the risk of diabetes among men.

Paternal Folate Status and Sperm Quality, Pregnancy Outcomes and Epigenetics; A Systematic Review and Meta-Analysis.
Hoek J, Steegers-Theunissen RPM, Willemsen SP, Schoenmakers S.
Mol Nutr Food Res. 2020 Feb 7:e1900696. doi: 10.1002/mnfr.201900696. [Epub ahead of print] Review.
PMID: 32032459
Abstract
SCOPE:
The effectiveness of maternal folate in reducing the risk of congenital malformations during pregnancy is well established. However, the role of the paternal folate status is scarcely investigated. The aim of this study is to investigate the evidence of associations between the paternal folate status and sperm quality, sperm epigenome and pregnancy outcomes.
METHODS AND RESULTS:
Databases were searched up to December 2017 resulting in 3682 articles, of which 23 were retrieved for full-text assessment. 4 out of 13 human and 2 out of 4 animal studies showed positive associations between folate concentrations and sperm parameters. An additional meta-analysis of 4 randomized controlled trials in subfertile men showed that the sperm concentration increases (3.54 95%CI (-1.40 to 8.48)) after 3-6 months of 5 mg folic acid use per day compared to controls. Moreover, 2 out of 2 animal and 1 out of 3 human studies showed significant alterations in the overall methylation of the sperm epigenome. 1 animal and 1 human study showed associations between low folate intake and an increased risk of congenital malformations.
CONCLUSIONS:
This systematic review and meta-analysis shows evidence of associations between the paternal folate status and sperm quality, fertility, congenital malformations and placental weight. This article is protected by copyright. All rights reserved.
KEYWORDS:
embryonic growth and congenital malformations; epigenetics; fertility; folate; folic acid; one-carbon metabolism; placenta; sperm

Supplemental one-carbon metabolism related B vitamins and lung cancer risk in the Women's Health Initiative.
Brasky TM, Ray RM, Navarro SL, Schenk JM, Newton AM, Neuhouser ML.
Int J Cancer. 2020 Feb 6. doi: 10.1002/ijc.32913. [Epub ahead of print]
PMID: 32030745
Abstract
We and others have reported associations between B vitamins principally involved in one-carbon metabolism and increased lung cancer risk; however results for women have been inconsistent. Here we report on the association of supplemental vitamins B6 , folic acid, and B12 intake and lung cancer risk using data from the Women's Health Initiative (WHI) study of postmenopausal women. Between 1993 and 1998, 161,808 women were recruited to participate in the WHI at 40 clinical centers in the US. After exclusions, 159,232 women were available for analysis and followed prospectively for an average of 18.3 years. Among them, 3,836 incident lung cancer cases were diagnosed. At baseline, supplemental B vitamins from multivitamins, vitamin mixtures, and individual supplements were assessed. Adjusted Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between supplemental B vitamin intake and lung cancer risk. Relative to no intake, women who took ≥50 mg/d of vitamin B6 had 16% (HR 0.84, 95% CI: 0.71-0.99) reduced lung cancer risk. Associations did not differ significantly by smoking status or lung cancer histology. Intakes of folic acid and vitamin B12 were not associated with risk. There is a need for replication of our findings from other large, prospective studies with similar high-quality measurement of supplement intakes before any recommendations can be made at present on B6 supplementation for lung cancer prevention in women.

Processed meat intake and incidence of colorectal cancer: a systematic review and meta-analysis of prospective observational studies.
Händel MN, Rohde JF, Jacobsen R, Nielsen SM, Christensen R, Alexander DD, Frederiksen P, Heitmann BL.
Eur J Clin Nutr. 2020 Feb 6. doi: 10.1038/s41430-020-0576-9. [Epub ahead of print] Review.
PMID: 32029911
Abstract
The objective was to use accumulated evidence to explore the association between processed meat intake and risk of colorectal cancer (CRC) and to investigate the reliability of associations by evaluating patterns of risk by study population characteristics and research quality parameters. We included 29 observational prospective cohort studies with relative risk estimates and 95% confidence intervals for CRC according to various levels of processed meat consumption. Risk of bias was assessed using Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) tool. Data sources were PubMed and Embase up to January 2017. The summary relative risks for high versus low processed meat consumption and risk of CRC, colon, and rectal cancer were 1.13 (95% CI: 1.01, 1.26), 1.19 (95% CI: 1.09, 1.31), and 1.21 (95% CI: 0.98, 1.49), respectively. Similar estimates were observed for the dose-response analyses. Heterogeneity across studies was detected in most analytical models. The overall judgment showed that two out of 29 studies had a moderate risk of bias, 25 had a serious risk of bias, and 2 had a critical risk of bias. The bias domains most often rated critical were bias due to risk of confounding, bias due to missing data, and selective outcome reporting bias. Although this meta-analysis indicates a modest association between processed meat intake and an increased risk of CRC, our assessment of internal validity warrants a cautious interpretation of these results, as most of the included studies were judged to have serious or critical risks of bias.

Effect of green tea supplementation on blood pressure: A systematic review and meta-analysis of randomized controlled trials.
Xu R, Yang K, Ding J, Chen G.
Medicine (Baltimore). 2020 Feb;99(6):e19047. doi: 10.1097/MD.0000000000019047.
PMID: 32028419 Free Article
https://journals.lww.com/md-journal/FullText/2020/02070/Effect_of_green_tea_supplementation_on_blood.36.aspx
Abstract
BACKGROUND:
Although evidence from animal and observational studies has supported the beneficial effects of green tea intake for lowering blood pressure (BP), randomized placebo-controlled trials (RCTs) have yielded conflicting results. In this meta-analysis of RCTs, we aimed to assess the effects of green tea supplementation on measures of BP control.
METHODS:
The PubMed, Embase, and Cochrane Library databases were electronically searched from inception to August 2019 for all relevant studies. The results were pooled using the generic inverse-variance method with random-effects weighting and expressed as mean differences (MDs) with 95% confidence intervals (CIs). The quality of studies was assessed using the Jadad score. Publication bias was evaluated using funnel plots, Egger test, and Begg test.
RESULTS:
Twenty-four trials with 1697 subjects were included in the meta-analysis. The pooled results showed that green tea significantly lowered systolic BP (SBP; MD: -1.17 mm Hg; 95%CI: -2.18 to -0.16mm Hg; P = .02) and diastolic BP (DBP; MD: -1.24 mm Hg; 95%CI:-2.07 to -0.40mm Hg; P = .004). Significant heterogeneity was found for both SBP (I = 43%) and DBP (I = 57%). In addition, no evidence of significant publication bias was found from funnel plots or Egger test (P = .674 and P = .270 for SBP and DBP, respectively).
CONCLUSION:
Overall, green tea significantly reduced SBP and DBP over the duration of the short-term trials. Larger and longer-term trials are needed to further investigate the effects of green tea supplementation on BP control and clinical events.

Association of Red Meat Usual Intake with Serum Ferritin and the Risk of Metabolic Syndrome in Chinese Adults: A Longitudinal Study from the China Health and Nutrition Survey.
Huang LN, Wang HJ, Wang ZH, Zhang JG, Jia XF, Zhang B, Ding GQ.
Biomed Environ Sci. 2020 Jan 20;33(1):19-29. doi: 10.3967/bes2020.003.
PMID: 32029055 Free Article
Abstract
OBJECTIVE:
The present study aimed to investigate the association of red meat usual intake with metabolic syndrome (MetS), and explore the contribution of red meat usual intake to serum ferritin.
METHODS:
Based on the data from the longitudinal China Health and Nutrition Survey (CHNS), 2,797 healthy adults aged 18-75 years without hypertension, diabetes, and MetS were selected in 2009 as subjects and follow-up studies were carried out till 2015. We used the National Cancer Institute (NCI) method to estimate the usual intake of foods. Multivariable logistic regressions were performed to evaluate the association between red meat usual intake and the risk of MetS. Quantile regression analysis was used to study the relationship between red meat consumption and serum ferritin levels.
RESULTS:
After adjusting for potential confounders, red meat, and fresh red meat were positively associated with the risk of MetS ( RR = 1.41, 95% CI: 1.05-1.90 and RR = 1.37, 95% CI: 1.02-1.85, respectively). These relationships showed increasing trend ( P < 0.05). The level of serum ferritin increased significantly with the number of MetS components ( P < 0.05). The quantile regression analysis showed that red meat and fresh red meat usual intake had a significant positive association with serum ferritin levels across the entire conditional serum ferritin distribution ( P < 0.05). Processed red meat did not exhibit a similar association.
CONCLUSION:
Higher red meat usual intake was associated with an increased risk of MetS and elevated serum ferritin levels.
KEYWORDS:
Metabolic syndrome; Red meat; Serum ferritin; Usual intake

Dietary intake of polyunsaturated fatty acids alleviates cognition deficits and depression-like behaviour via cannabinoid system in sleep deprivation rats.
Wang T, Niu K, Fan A, Bi N, Tao H, Chen XT, Wang HL.
Behav Brain Res. 2020 Feb 6:112545. doi: 10.1016/j.bbr.2020.112545. [Epub ahead of print]
PMID: 32035867
Abstract
Sleep deprivation (SD) is a common feature in modern society. Prolonged sleep deprivation causes cognition deficits and depression-like behavior in the model of animal experiments. Endocannabinoid system are key modulators of synaptic function, which were related to memory and mood. Although the underlying mechanism remains unknown, several studies indicated the benefits of polyunsaturated fatty acids (PUFAs, linolenic acid, 39.7%; linoleic acid, 28%; and oleic acid, 22%) on brain function through the endocannabinoid system. The present study aimed to evaluate the influence of dietary PUFAs on cognition deficits induced by sleep deprivation in Sprague Dawley rats. The rats were sleep deprivation continuously for 7 days and fed with PUFAs at three different dosages (2, 4 and 8 μl/g body weight) at the meantime. The effect of PUFAs on cognition was investigated by object recognition test while depressive-like behavior were detected using sucrose preference test and forced swim test. The mechanism of PUFAs was elucidated by hippocampal synaptic transmission analyses. The resluts revealed that SD led to the disorder of cognition and mood which was improved by the supplement of PUFAs. SD significantly increased the mEPSC frequency, and decreased the protein level of cannabinoid type-1 receptors (CB1R). These changes were restored by supplement of PUFAs, which showed a similar level to the control group. Behaviour tests showed that the positive effects on repairing cognition and anxiety disorders were almost completely abolished when the CB1R receptor antagonist rimonabant was applied to the SD rats. These findings indicated that PUFAs are a factor regulating cognition deficits and depression induced by SD via cannabinoid type-1 receptors.
KEYWORDS:
anxiety; cannabinoid type-1 receptor; cognition; polyunsaturated fatty acids; sleep deprivation

The effect of coffee consumption on insulin sensitivity and other biological risk factors for type 2 diabetes: a randomized placebo-controlled trial.
Alperet DJ, Rebello SA, Khoo EY, Tay Z, Seah SS, Tai BC, Tai ES, Emady-Azar S, Chou CJ, Darimont C, van Dam RM.
Am J Clin Nutr. 2020 Feb 1;111(2):448-458. doi: 10.1093/ajcn/nqz306.
PMID: 31891374
Abstract
BACKGROUND:
In observational studies, coffee consumption has been consistently associated with a lower risk of type 2 diabetes mellitus. Trials examining the effect of coffee consumption on glucose metabolism have been limited by the use of surrogate insulin sensitivity indices, small sample sizes, lack of blinding, and short follow-up duration.
OBJECTIVES:
We aimed to overcome limitations of previously conducted coffee trials in a randomized placebo-controlled trial of the effect of coffee consumption on insulin sensitivity.
METHODS:
We conducted a 24-wk randomized placebo-controlled trial in 126 overweight, non-insulin sensitive (HOMA-IR ≥1.30), Chinese, Malay, and Asian-Indian males and females aged 35-69 y. Participants were randomly assigned to receive 4 cups of instant regular coffee (n = 62) or 4 cups of a coffee-like placebo beverage (n = 64) per day. The primary outcome was the amount of glucose metabolized per kilogram of body weight per minute (Mbw) assessed during steady-state conditions with a hyperinsulinemic euglycemic clamp. Secondary outcomes included other clamp-based insulin sensitivity measures, biological mediators of insulin sensitivity, and measures of fasting glucose metabolism.
RESULTS:
Coffee consumption did not significantly change insulin sensitivity compared with placebo (percentage mean difference in Mbw = 4.0%; 95% CI: -8.3, 18.0%; P = 0.53). Furthermore, no significant differences in fasting plasma glucose (2.9%; 95% CI: -0.4, 6.3%; P = 0.09) or biological mediators of insulin resistance, such as plasma adiponectin (2.3%; 95% CI: -1.4, 6.2%; P = 0.22), were observed between coffee and placebo groups over 24 wk of intervention. Participants in the coffee arm experienced a loss of fat mass (FM) (-3.7%; 95% CI: -6.3, -1.1%; P = 0.006) and reduction in urinary creatinine concentrations (-21.2%; 95% CI: -31.4, -9.5%; P = 0.001) compared with participants in the placebo arm over 24 wk of intervention.
CONCLUSIONS:
Consuming 4 cups/d of caffeinated coffee for 24 wk had no significant effect on insulin sensitivity or biological mediators of insulin resistance but was associated with a modest loss of FM and reduction in urinary creatinine concentrations.This trial was registered at clinicaltrials.gov as NCT01738399. Registered on November 28, 2012. Trial sponsor: Nestlé Research, Lausanne, Switzerland. Trial site: National University of Singapore.
KEYWORDS:
adult-onset diabetes mellitus; coffee; humans; hyperinsulinemic euglycemic clamp; insulin resistance; insulin sensitivity; metabolic health; type 2 diabetes

Red and processed meat consumption and the risk of esophageal and gastric cancer subtypes in The Netherlands Cohort Study.
Keszei AP, Schouten LJ, Goldbohm RA, van den Brandt PA.
Ann Oncol. 2012 Sep;23(9):2319-2326. doi: 10.1093/annonc/mdr615. Epub 2019 Dec 4.
PMID: 32018704
Abstract
BACKGROUND:
Prospective data on red and processed meat in relation to risk of subtypes of esophageal and gastric cancer are scarce. We present analyses of association between red and processed meat and the risk of esophageal and gastric cancer subtypes within The Netherlands Cohort Study on Diet and Cancer.
DESIGN:
120852 individuals aged 55-69 years were recruited in 1986, and meat intake was assessed using a 150-item food frequency questionnaire. After 16.3 years of follow-up, 107 esophageal squamous cell carcinomas, 145 esophageal adenocarcinomas, 163 gastric cardia adenocarcinomas, 489 gastric non-cardia adenocarcinomas, and 3923 subcohort members were included in a case-cohort analysis.
RESULTS:
Processed as well as red meat intake was positively associated with esophageal squamous cell carcinoma in men. Hazard ratios for highest versus lowest quintile of processed and red meat were 3.47 [95% confidence intervals (CI): 1.21-9.94; P for trend: 0.04] and 2.66 (95% CI: 0.94-7.48; P for trend: 0.06), respectively. No association was seen for adenocarcinomas or gastric cancer subtypes or for any of the four subtypes among women.
CONCLUSION:
Our findings suggest that red and processed meat consumption is associated with increased risk of esophageal squamous cell carcinoma in men but not with cancers of other esophageal and gastric subtypes.
KEYWORDS:
cohort studies; esophageal neoplasms; processed meat; red meat; stomach neoplasms

Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and risk of liver and biliary tract cancers in Western Europeans.
Fedirko V, Lukanova A, Bamia C, Trichopolou A, Trepo E, Nöthlings U, Schlesinger S, Aleksandrova K, Boffetta P, Tjønneland A, Johnsen NF, Overvad K, Fagherazzi G, Racine A, Boutron-Ruault MC, Grote V, Kaaks R, Boeing H, Naska A, Adarakis G, Valanou E, Palli D, Sieri S, Tumino R, Vineis P, Panico S, Bueno-de-Mesquita HBA, Siersema PD, Peeters PH, Weiderpass E, Skeie G, Engeset D, Quirós JR, Zamora-Ros R, Sánchez MJ, Amiano P, Huerta JM, Barricarte A, Johansen D, Lindkvist B, Sund M, Werner M, Crowe F, Khaw KT, Ferrari P, Romieu I, Chuang SC, Riboli E, Jenab M.
Ann Oncol. 2013 Feb;24(2):543-553. doi: 10.1093/annonc/mds434. Epub 2019 Dec 4.
PMID: 32018434
Abstract
BACKGROUND:
The type and quantity of dietary carbohydrate as quantified by glycemic index (GI) and glycemic load (GL), and dietary fiber may influence the risk of liver and biliary tract cancers, but convincing evidence is lacking.
PATIENTS AND METHODS:
The association between dietary GI/GL and carbohydrate intake with hepatocellular carcinoma (HCC; N = 191), intrahepatic bile duct (IBD; N = 66), and biliary tract (N = 236) cancer risk was investigated in 477 206 participants of the European Prospective Investigation into Cancer and Nutrition cohort. Dietary intake was assessed by country-specific, validated dietary questionnaires. Hazard ratios and 95% confidence intervals were estimated from proportional hazard models. HBV/HCV status was measured in a nested case-control subset.
RESULTS:
Higher dietary GI, GL, or increased intake of total carbohydrate was not associated with liver or biliary tract cancer risk. For HCC, divergent risk estimates were observed for total sugar = 1.43 (1.17-1.74) per 50 g/day, total starch = 0.70 (0.55-0.90) per 50 g/day, and total dietary fiber = 0.70 (0.52-0.93) per 10 g/day. The findings for dietary fiber were confirmed among HBV/HCV-free participants [0.48 (0.23-1.01)]. Similar associations were observed for IBD [dietary fiber = 0.59 (0.37-0.99) per 10 g/day], but not biliary tract cancer.
CONCLUSIONS:
Findings suggest that higher consumption of dietary fiber and lower consumption of total sugars are associated with lower HCC risk. In addition, high dietary fiber intake could be associated with lower IBD cancer risk.
KEYWORDS:
biliary tract neoplasms; dietary carbohydrate; dietary fiber; glycemic index; hepatocellular carcinoma; liver neoplasms

A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study.
Chajès V, Assi N, Biessy C, Ferrari P, Rinaldi S, Slimani N, Lenoir GM, Baglietto L, His M, Boutron-Ruault MC, Trichopoulou A, Lagiou P, Katsoulis M, Kaaks R, Kühn T, Panico S, Pala V, Masala G, Bueno-de-Mesquita HB, Peeters PH, van Gils C, Hjartåker A, Standahl Olsen K, Borgund Barnung R, Barricarte A, Redondo-Sanchez D, Menéndez V, Amiano P, Wennberg M, Key T, Khaw KT, Merritt MA, Riboli E, Gunter MJ, Romieu I.
Ann Oncol. 2017 Nov;28(11):2836-2842. doi: 10.1093/annonc/mdx482. Epub 2019 Dec 4.
PMID: 32014218
https://watermark.silverchair.com/mdx482.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAmIwggJeBgkqhkiG9w0BBwagggJPMIICSwIBADCCAkQGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMYavWBvDZ10sIxgZhAgEQgIICFaPcWHtdhmmgHHbK50gvNpLRe8fK30A9NCyiWW_acVhTlofb1kUySrgptYg3L9eH6PGzYBnB8bTHeTKH4vvaZ2pmHO1DbjXRXjcVl0DmNGY5gs4qMK6FFSV-PLXSB3yFPiUFmk-TkFatKcyGTVgK70Y0WO4wnW9u5NKuxWlr_3TJAht6oYnsFF1oWdFokC8dM3ZW1HPrXLdqNyfcnUUmTk-4a_lqWdMGf5z_GqPvqCTItQJFMM8W49dJ5vHqHGS-I3ZD7hysQoyXwnjiD_fluKDNMmofwd8VOfRyCoJ125Q2piC3AyboDpBLXkw9Hv-CqzDhNbjcMv9z7jG4jYJ7x7SSffd9z8cYvrddlBC9KSmeJTTZeUabwdDBv02fsxD5UgmyM6s7q4xI7Pc_htL0nAiYXPaSqGeWJEouSwjgKV-33euc8a78UU3vfeQ1lbzX7LZosxIFPwX-6x22S4gEPp_8CheHg7bNmeNvJunipa17eICfG3NceqMf7kghvNleA5oBR8-iw1RmFkC8UJkiIxk23nfxbe0Xc97xdY-F7K1EKajyggyaAo4BOJgjOzqtAXQfvYhtdR8HSQrhXyUK1fr4T0EkA3HKcw_pDIyjeMW1i4-1ly2COcn_OZ9UuQeGwKtmQ7StkBA88MLG1-4Edv2BUfhRhLz5mUBIMQYDBK2UxMVqIsXZBAGaLnf8fNi1FuF0Y465
Abstract
BACKGROUND:
Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting.
MATERIALS AND METHODS:
We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours.
RESULTS:
A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend=0.0001, q value=0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend=0.002, q value=0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend=0.047], whereas no association was found for ER-positive tumours (P-heterogeneity=0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor.
CONCLUSION:
These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.
KEYWORDS:
EPIC; biomarkers; breast cancer; epidemiology; fatty acids

Separating the effects of 24-hour urinary chloride and sodium excretion on blood pressure and risk of hypertension: Results from PREVEND.
van der Leeuw J, de Borst MH, Kieneker LM, Bakker SJL, Gansevoort RT, Rookmaaker MB.
PLoS One. 2020 Feb 5;15(2):e0228490. doi: 10.1371/journal.pone.0228490. eCollection 2020.
PMID: 32023312 Free Article
Abstract
OBJECTIVE:
Research into dietary factors associated with hypertension has focused on the sodium component of salt. However, chloride has distinct physiological effects that may surpass the effect of sodium on blood pressure. This study aims to separate the specific effects of chloride and sodium intake on blood pressure.
METHODS:
We studied 5673 participants from the Prevention of Renal and Vascular End-Stage Disease(PREVEND) study. Urinary chloride(uCl) and sodium(uNa) were measured in two 24-hour collections. We used generalized-linear-regression to evaluate the relation of uCl and uNa with baseline blood pressure and Cox-proportional-hazards-analysis to assess the association with hypertension. Multicollinearity was assessed with Ridge regression.
RESULTS:
Baseline 24-hour uCl was 135±39mmol and uNa was 144±54mmol. The correlation between uCl and uNa was high (Pearson's r = 0.96). UCl and uNa had similar non-significant positive and linear associations with blood pressure. In 3515 normotensive patients, 1021 patients developed hypertension during a median follow-up of 7.4 years. UCl and uNa had a comparable but non-significant J-shaped effect on the risk of hypertension. Adding both uCl and uNa to the same model produced instability, demonstrated by Ridge coefficients that converged or changed sign. The single index of uNa minus uCl showed a non-significant higher risk of hypertension of 2% per 10mmol/24-hour difference (HR1.02, 95%CI 0.98-1.06).
CONCLUSION:
UCl and uNa had similar positive but non-significant associations with blood pressure and risk of hypertension and their effects could not be disentangled. Hence, the alleged adverse effects of high salt intake could be due to sodium, chloride or both. This encourages further study into the effect of chloride in order to complement dietary recommendations currently focused on sodium alone.

Fasting Serum Levels of Potassium and Sodium in Relation to Long-Term Risk of Cancer in Healthy Men.
Falk RS, Heir T, Robsahm TE, Tretli S, Sandvik L, Erikssen JE, Paulsen JE.
Clin Epidemiol. 2020 Jan 9;12:1-8. doi: 10.2147/CLEP.S216438. eCollection 2020.
PMID: 32021466 Free PMC Article
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959139/pdf/clep-12-1.pdf
Abstract
PURPOSE:
To examine whether serum levels of potassium and sodium were associated with long-term cancer risk in initially healthy men.
PATIENTS AND METHODS:
A cohort of 1994 initially healthy men with no use of medication, aged 40-59 years, was followed for cancer during 40 years of follow-up. Associations between fasting electrolyte levels and cancer risk were assessed with incidence rates and Cox proportional hazards models.
RESULTS:
Potassium, but not sodium, was linearly associated with cancer risk. This association remained significant after adjustment of several potential confounding factors, and also after excluding the first 10 years of follow-up. The age-adjusted risk of all-site cancer increased with 16% for each SD increase in potassium level. Men with hyperkalemia showed an incidence rate that was 40% higher than for men with normal potassium levels.
CONCLUSION:
Fasting serum potassium level in healthy men was positively associated with long-term cancer risk. Potassium or potassium ion channels may have a role in cell proliferation or differentiation. These findings might imply future cancer strategies for targeting individuals with high serum potassium levels.
KEYWORDS:
cancer incidence; cell proliferation; electrolyte levels; epidemiology; prospective cohort study

Skipping breakfast before and during early pregnancy and incidence of gestational diabetes mellitus: the Japan Environment and Children's Study.
Dong JY, Ikehara S, Kimura T, Cui M, Kawanishi Y, Kimura T, Ueda K, Iso H; Japan Environment and Children's Study Group.
Am J Clin Nutr. 2020 Feb 5. pii: nqaa014. doi: 10.1093/ajcn/nqaa014. [Epub ahead of print]
PMID: 32020171
Abstract
BACKGROUND:
There is little evidence linking breakfast skipping to the incidence of gestational diabetes mellitus (GDM).
OBJECTIVES:
We aimed to evaluate the prospective association of breakfast consumption with the incidence of GDM.
METHODS:
A total of 103,099 pregnancies were registered during study enrollment (January 2011 to March 2014), involving 97,454 pregnant women from 15 areas across Japan. Singleton pregnant women free of GDM, stroke, heart disease, cancer, and type 1 or type 2 diabetes at the study enrollment were eligible for analysis. We used a self-administered questionnaire to obtain data on demographic information, socioeconomic status, self-rated health status, disease history, lifestyle, and dietary habits of each woman at study enrollment. A semiquantitative FFQ was used for dietary assessment. We used logistic regression to obtain the OR of GDM in relation to breakfast consumption.
RESULTS:
Among 84,669 pregnant women for analysis, 1935 cases of GDM were documented. After adjustment for potential confounding factors including prepregnancy BMI, the multivariable-adjusted ORs of GDM for women who consumed breakfast 5-6 times/wk, 3-4 times/wk, and 0-2 times/wk were 1.09 (95% CI: 0.93, 1.27), 1.14 (95% CI: 0.96, 1.34), and 1.21 (95% CI: 1.05, 1.41), respectively, compared with daily breakfast eaters. The association appeared to be dose dependent (P-trend = 0.006) and was not significantly modified by prepregnancy BMI.
CONCLUSIONS:
Breakfast consumption ❤️ times/wk before and during early pregnancy, compared with daily consumption, was associated with an increased odds of developing GDM.
KEYWORDS:
breakfast; cohort study; gestational diabetes; pregnancy; prevention

Dietary intake and biomarkers of linoleic acid and mortality: systematic review and meta-analysis of prospective cohort studies.
Li J, Guasch-Ferré M, Li Y, Hu FB.
Am J Clin Nutr. 2020 Feb 5. pii: nqz349. doi: 10.1093/ajcn/nqz349. [Epub ahead of print]
PMID: 32020162
Abstract
BACKGROUND:
Current evidence on associations between intakes of linoleic acid (LA), the predominant n-6 (ω-6) fatty acid, and mortality is inconsistent and has not been summarized by a systematic review and meta-analysis.
OBJECTIVE:
The aim was to perform a systematic review and meta-analysis of prospective cohort studies to examine associations between LA intake and mortality.
METHODS:
We conducted a comprehensive search of MEDLINE and EMBASE databases through 31 July 2019 for prospective cohort studies reporting associations of LA (assessed by dietary surveys and/or LA concentrations in adipose tissue or blood compartments) with mortality from all causes, cardiovascular disease (CVD), and cancer. Multivariable-adjusted RRs were pooled using random-effects meta-analysis.
RESULTS:
Thirty-eight studies reporting 44 prospective cohorts were identified; these included 811,069 participants with dietary intake assessment (170,076 all-cause, 50,786 CVD, and 59,684 cancer deaths) and 65,411 participants with biomarker measurements (9758 all-cause, 6492 CVD, and 1719 cancer deaths). Pooled RRs comparing extreme categories of dietary LA intake (high vs low) were 0.87 (95% CI: 0.81, 0.94; I2 = 67.9%) for total mortality, 0.87 (95% CI: 0.82, 0.92; I2 = 3.7%) for CVD mortality, and 0.89 (95% CI: 0.85, 0.93; I2 = 0%) for cancer mortality. Pooled RRs for each SD increment in LA concentrations in adipose tissue/blood compartments were 0.91 (95% CI: 0.87, 0.95; I2 = 64.1%) for total mortality, 0.89 (95% CI: 0.85, 0.94; I2 = 28.9%) for CVD mortality, and 0.91 (95% CI: 0.84, 0.98; I2 = 26.3%) for cancer mortality. Meta-regressions suggested baseline age and dietary assessment methods as potential sources of heterogeneity for the association between LA and total mortality.
CONCLUSIONS:
In prospective cohort studies, higher LA intake, assessed by dietary surveys or biomarkers, was associated with a modestly lower risk of mortality from all causes, CVD, and cancer. These data support the potential long-term benefits of PUFA intake in lowering the risk of CVD and premature death.
KEYWORDS:
biomarkers; cardiovascular disease; dietary polyunsaturated fatty acid; linoleic acid; mortality

15-Year lipid profile effects on cardiovascular events adjusted for cardiovascular risk factors: a cohort study from Middle-East.
Sadeghi M, Golshahi J, Talaei M, Sheikhbahaei E, Ghodjani E, Mansouri M, Mansouri P, Sarrafzadegan N, Roohafza H.
Acta Cardiol. 2020 Feb 5:1-6. doi: 10.1080/00015385.2020.1717096. [Epub ahead of print]
PMID: 32019473
https://sci-hub.tw/https://www.tandfonline.com/doi/full/10.1080/00015385.2020.1717096
Abstract
Background: Dyslipidaemia is a risk factor for cardiovascular disease (CVD); however, there are only a few long-term cohort studies. The aim of this unique study is to evaluate the effects of several lipid markers on cardiovascular outcomes during a 15-year follow-up from the Isfahan cohort study (ICS).Methods: This ongoing cohort study was started in 2001 in three cities of Iran. The study population includes 5432 individuals older than 35 years and with Iranian citizenship. All of the patients were evaluated every 2 years by telephone and a full medical examination with blood sampling was conducted every 5 years. The data were recorded in our checklists. Dyslipidaemia was defined according to the ATPIII criteria. Our endpoints in this study were any cardiovascular events such as stroke, sudden cardiac death, unstable angina or myocardial infarction (MI).Results: cardiovascular events were significantly higher in males, older people, diabetics, smokers, patients with higher BMIs, higher blood pressure, dyslipidaemia and less educational level, physical activity index and global dietary index. Our adjusted multivariable analysis (for cardiovascular risk factors and demographic factors) revealed that dyslipidaemia could increase the risk of 15-year cardiovascular events by 1.59 times (HR = 1.59 [1.23-2.06], p value  < .001) adjusted for demographic factors and baseline cardiovascular risk factors.Conclusions: Dyslipidaemia, as an independent risk factor, was associated with future cardiovascular events. In this regard, serum lipid screening can help to decrease the risk of long-term cardiovascular events.
KEYWORDS:
Lipid; cardiovascular diseases; cardiovascular events; cohort studies; dyslipidaemias; risk factor

Urinary Albumin, Sodium, and Potassium and Cardiovascular Outcomes in the UK Biobank: Observational and Mendelian Randomization Analyses.
Zanetti D, Bergman H, Burgess S, Assimes TL, Bhalla V, Ingelsson E.
Hypertension. 2020 Feb 3:HYPERTENSIONAHA11914028. doi: 10.1161/HYPERTENSIONAHA.119.14028. [Epub ahead of print]
PMID: 32008434
Abstract
Urinary biomarkers are associated with cardiovascular disease, but the nature of these associations is not well understood. We performed multivariable-adjusted regression models to assess associations of random spot measurements of the urine sodium-potassium ratio (UNa/UK) and urine albumin adjusted for creatinine with cardiovascular risk factors, cardiovascular disease, and type 2 diabetes mellitus (T2D) in 478 311 participants of the UK Biobank. Further, we assessed the causal relationships of these kidney biomarkers, used as proxies for kidney function, with cardiovascular outcomes using the 2-sample Mendelian randomization approach. In observational analyses, UNa/UK showed significant inverse associations with atrial fibrillation, coronary artery disease, ischemic stroke, lipid-lowering medication, and T2D. In contrast, urine albumin adjusted for creatinine showed significant positive associations with atrial fibrillation, coronary artery disease, heart failure, hemorrhagic stroke, lipid-lowering medication, and T2D. We found a positive association between UNa/UK and albumin with blood pressure (BP), as well as with adiposity-related measures. After correcting for potential horizontal pleiotropy, we found evidence of causal associations of UNa/UK and albumin with BP (β systolic BP ≥2.63; β diastolic BP ≥0.85 SD increase in BP per SD change in UNa/UK and urine albumin adjusted for creatinine; P≤0.04), and of albumin with T2D (odds ratio=1.33 per SD change in albumin, P=0.02). Our comprehensive study of urinary biomarkers performed using state-of-the-art analyses of causality mirror and extend findings from randomized interventional trials which have established UNa/UK as a risk factor for hypertension. In addition, we detect a causal feedback loop between albumin and hypertension, and our finding of a bidirectional causal association between albumin and T2D reflects the well-known nephropathy in T2D.
KEYWORDS:
blood pressure; cardiovascular diseases; coronary artery disease; heart failure; type 2 diabetes mellitus

Associations of serum uric acid with total and cause-specific mortality: Findings from individuals and pooling prospective studies.
Mazidi M, Katsiki N, Mikhailidis DP, Banach M; Lipid and Blood Pressure Meta-Analysis Collaboration (LBPMC) Group.
Atherosclerosis. 2019 Jul 20;296:49-58. doi: 10.1016/j.atherosclerosis.2019.07.019. [Epub ahead of print] Review.
PMID: 32032905
Abstract
BACKGROUND AND AIMS:
There is considerable controversy regarding the link between serum uric acid (SUA) and mortality. We prospectively evaluated the association between SUA and risk of total and cause specific (coronary heart disease [CHD], cerebrovascular and cancer) mortality by using the National Health and Nutrition Examination Surveys (NHANES, 1999-2010). Furthermore, a systematic review and meta-analysis of cohort studies was performed to investigate pooled associations of SUA with all-cause and cause-specific mortality.
METHODS:
Vital status through December 31, 2011 was ascertained. PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched (up to April 2018). Adjusted Cox proportional hazard regression models were used to determine the association between SUA and mortality. The DerSimonian-Laird method and generic inverse variance methods were used for quantitative data synthesis.
RESULTS:
Overall, 21,025 individuals were included (mean age = 47.6 years, 48.7% men) and 3520 deaths occurred during the 144 months of follow-up. In adjusted models, individuals in the highest quartile of SUA had 10 and 8% greater risk of CHD and stroke mortality, whereas there was no link between SUA, all-cause and cancer mortality. The associations of CHD and stroke mortality with SUA were more pronounced in women and, among women, in those aged >50 years. Furthermore, all-cause mortality was positively and significantly related to SUA concentrations only in women. In the meta-analysis, SUA was shown to predict the risk of total (21%), CHD (24%) and stroke (29%) mortality. Furthermore, participants with a higher level of central adiposity had a greater risk of mortality from CHD and stroke for the same level of SUA.
CONCLUSIONS:
Our results highlight the adverse impact of SUA on mortality, particularity in older (>50 years) women. The clinical implications of these findings remain to be established in future trials.
KEYWORDS:
Coronary heart disease; Meta-analysis; Mortality; Serum uric acid; Stroke

Meta-analytic evidence for the anti-aging effect of hormesis on Caenorhabditis elegans.
Sun T, Wu H, Cong M, Zhan J, Li F.
Aging (Albany NY). 2020 Feb 7;12. doi: 10.18632/aging.102773. [Epub ahead of print]
PMID: 32031985
Abstract
Mild stress-induced hormesis, as a promising strategy to improve longevity and healthy aging, meets both praise and criticism. To comprehensively assess the applicability of hormesis in aging intervention, this meta-analysis was conducted focusing on the effect of hormesis on Caenorhabditis elegans. Twenty-six papers involving 198 effect size estimates met the inclusion criteria. Meta-analytic results indicated that hormesis could significantly extend the mean lifespan of C. elegans by 16.7% and 25.1% under normal and stress culture conditions (p < 0.05), respectively. The healthspan assays showed that hormesis remarkably enhanced the bending frequency and pumping rate of worms by 28.9% and 7.0% (p < 0.05), respectively, while effectively reduced the lipofuscin level by 15.9% (p < 0.05). The obviously increased expression of dauer formation protein-16 (1.66-fold) and its transcriptional targets, including superoxide dismutase-3 (2.46-fold), catalase-1 (2.32-fold) and small heat shock protein-16.2 (2.88-fold) (p < 0.05), was one of the molecular mechanisms underlying these positive effects of hormesis. This meta-analysis provided strong evidence for the anti-aging role of hormesis, highlighting its lifespan-prolonging, healthspan-enhancing and resistance-increasing effects on C. elegans. Given that dauer formation protein-16 was highly conservative, hormesis offered the theoretical possibility of delaying intrinsic aging through exogenous intervention among humans.
KEYWORDS:
Caenorhabditis elegans; aging; anti-aging; hormesis; meta-analysis

Consequences of physical inactivity in older adults: A systematic review of reviews and meta-analyses.
Cunningham C, O' Sullivan R, Caserotti P, Tully MA.
Scand J Med Sci Sports. 2020 Feb 4. doi: 10.1111/sms.13616. [Epub ahead of print] Review.
PMID: 32020713
https://sci-hub.tw/10.1111/sms.13616
Abstract
BACKGROUND:
Globally, populations are ageing. Typically, physical activity levels decline and health worsens as we age; however, estimates of the impact of physical inactivity for population health often fail to specifically focus on older adults.
METHODS:
Multiple databases were searched for systematic reviews and/or meta-analyses of longitudinal observational studies, investigating the relationship between physical activity and any physical or mental health outcome in adults aged ≥60 years. Quality of included reviews was assessed using AMSTAR.
RESULTS:
Twenty-four systematic reviews and meta-analyses were included. The majority of reviews were of moderate or high methodological quality. Physically active older adults (≥60 years) are at a reduced risk of all-cause and cardiovascular mortality, breast and prostate cancer, fractures, recurrent falls, ADL disability and functional limitation and cognitive decline, dementia, Alzheimer's disease, and depression. They also experience healthier ageing trajectories, better quality of life and improved cognitive functioning.
CONCLUSION:
This review of reviews provides a comprehensive and systematic overview of epidemiological evidence from previously conducted research to assess the associations of physical activity with physical and mental health outcomes in older adults.
KEYWORDS:
ageing; exercise; health; physical activity; systematic review

Vitamin D status, cognitive decline and incident dementia: the Canadian Study of Health and Aging.
Duchaine CS, Talbot D, Nafti M, Giguère Y, Dodin S, Tourigny A, Carmichael PH, Laurin D.
Can J Public Health. 2020 Feb 3. doi: 10.17269/s41997-019-00290-5. [Epub ahead of print]
PMID: 32016921
https://sci-hub.tw/10.17269/s41997-019-00290-5
Abstract
OBJECTIVE:
Vitamin D could prevent cognitive decline because of its neuroprotective, anti-inflammatory and antioxidant properties. This study aimed to evaluate the associations of plasma 25-hydroxyvitamin D (25(OH)D) concentrations with global cognitive function and incident dementia, including Alzheimer's disease (AD).
METHODS:
The Canadian Study of Health and Aging is a 10-year cohort study of a representative sample of individuals aged 65 years or older. A total of 661 subjects initially without dementia with frozen blood samples and follow-up data were included. Global cognitive function was measured using the validated Modified Mini-Mental State (3MS) examination. A consensus diagnosis of all-cause dementia and AD was made between the physician and the neuropsychologist according to published criteria. Cognitive decline for a 5-year increase in age at specific 25(OH)D concentrations was obtained using linear mixed models with repeated measures. Hazard ratios of incident dementia and AD were obtained using semi-parametric proportional hazards models with age as time scale.
RESULTS:
Over a mean follow-up of 5.4 years, 141 subjects developed dementia of which 100 were AD. Overall, no significant association was found between 25(OH)D and cognitive decline, dementia or AD. Higher 25(OH)D concentrations were associated with an increased risk of dementia and AD in women, but not in men.
CONCLUSION:
This study does not support a protective effect of vitamin D status on cognitive function. Further research is needed to clarify the relation by sex.
KEYWORDS:
25-hydroxyvitamin D; Alzheimer disease; Cognitive impairment; Prospective study

Association of Vitamin D Levels with Incident All-Cause Dementia in Longitudinal Observational Studies: A Systematic Review and Meta-analysis.
Kalra A, Teixeira AL, Diniz BS.
J Prev Alzheimers Dis. 2020;7(1):14-20. doi: 10.14283/jpad.2019.44.
PMID: 32010921
Abstract
BACKGROUND:
The role of vitamin D is not only limited to bone health and pathogenesis of chronic diseases. Evidence now suggests that it is also involved in the development of various dementias and Alzheimer's disease (AD).
OBJECTIVE:
To carry out a systematic review and meta-analysis to evaluate the association between vitamin D levels and increased risk of incident all-cause dementia in longitudinal studies.
DESIGN:
We conducted a systematic review and meta-analysis using the electronic bibliographic databases PubMed and Scopus.
SETTING:
Prospective cohort studies.
PARTICIPANTS:
Community-dwelling older adults.
MEASUREMENTS:
Vitamin D serum concentrations were categorized in three groups: normal levels (>50 nmol/L), insufficient levels (25 - 49.9 nmol/L), and deficient levels (<25 nmol/L). We performed a meta-analysis using the general inverse variance method to calculate the pooled risk of AD and all-cause dementia according to vitamin D levels. Random-effects or fixed-effect model were used to calculate the pooled risk based on the heterogeneity analysis.
RESULTS:
Five studies were included in the meta-analysis. The pooled risk of all-cause dementia and AD was significantly higher in those with deficient serum vitamin D level compared to those with normal level (1.33, CI95% [1.15, 1.54], and 1.87, CI95% [1.03, 3.41], respectively). Those with insufficient level also had a higher pooled risk of all-cause dementia and AD, but the strength of association was less robust (1.14 CI95% [1.02, 1.27] and 1.25, CI95% [1.04 - 1.51], respectively).
CONCLUSION:
We found a gradient effect for the risk of all-cause dementia and AD according to the vitamin D level, with higher risk in those in the deficient levels group and intermediate risk in those with insufficient levels. Our findings were limited by the relatively small number of studies included in the meta-analysis and their geographic restriction.
KEYWORDS:
Alzheimer’s disease; Vitamin D ; all-cause dementia; risk factor

Association Between Insomnia And Mortality Is Only Evident Among Long Sleepers.
Hedström AK, Bellocco R, Ye W, Trolle Lagerros Y, Åkerstedt T.
Nat Sci Sleep. 2019 Nov 13;11:333-342. doi: 10.2147/NSS.S222049. eCollection 2019.
PMID: 32009823 Free PMC Article
Abstract
BACKGROUND:
Previous studies investigating the relationship between insomnia and mortality have been inconsistent.
PURPOSE:
We aimed to assess whether nocturnal insomnia symptoms and non-restorative sleep are associated with all-cause mortality and whether they modify the associations between short and long sleep duration and all-cause mortality.
PATIENTS AND METHODS:
The present report is based on a prospective cohort study of 39,139 participants with a mean follow-up time of 19.6 years. Cox proportional hazard models with attained age as timescale were used to estimate overall mortality hazard ratios (HRs) with 95% confidence intervals (CI) for different categories of sleep duration and insomnia symptoms.
RESULTS:
Both difficulty initiating sleep and daytime sleepiness were independently associated with increased mortality among those with sleep duration of 9 hrs or more (HR 1.51, 95% CI 1.11-2.07 and HR 1.37, 95% CI 1.03-1.82). Mortality increased with increasing severity of difficulties initiating sleep (p for trend 0.04) and daytime sleepiness (p for trend 0.01) among the long sleepers. None of the insomnia symptoms were associated with mortality among those who reported sleep duration of 8 hrs or less.
CONCLUSION:
Long sleep in combination with difficulties initiating sleep and daytime sleepiness, possibly due to psychiatric or physical disorders, was thus associated with increased mortality, whereas long sleep without difficulties falling asleep or daytime sleepiness was not associated with mortality. Our study emphasizes the need to take nocturnal insomnia symptoms and daytime sleepiness into consideration when assessing the influence of sleep duration on mortality. Additional research is needed to elucidate the relationship between long sleep, insomnia and related psychiatric and physical disorders.
KEYWORDS:
prospective cohort study; sleep duration; sleep quality

The association between habitual sleep duration and mortality according to sex and age: the Japan Public Health Center-based Prospective Study.
Svensson T, Inoue M, Saito E, Sawada N, Iso H, Mizoue T, Goto A, Yamaji T, Shimazu T, Iwasaki M, Tsugane S.
J Epidemiol. 2020 Feb 1. doi: 10.2188/jea.JE20190210. [Epub ahead of print]
PMID: 32009104 Free Article
https://www.jstage.jst.go.jp/article/jea/advpub/0/advpub_JE20190210/_pdf/-char/en
Abstract
BackgroundShort and long sleep durations are associated with mortality outcomes. The association between sleep duration and mortality outcomes may differ according to sex and age.MethodsParticipants of the Japan Public Health Center-based prospective study (JPHC Study) were aged 40-69 years and had completed a detailed questionnaire on lifestyle factors. Sex- and age-stratified analyses on the association between habitual sleep duration and mortality from all-causes, cardiovascular diseases (CVD), cancer and other causes included 46,152 men and 53,708 women without a history of CVD or cancer. Cox proportional hazards regression models, adjusted for potential confounders, were used to determine hazard ratios and 95% confidence intervals.ResultsMean follow-up time was 19.9 years for men and 21.0 years for women. In the multivariable sex-stratified models, and compared with 7 hours, some categories of sleep durations ≥ 8 hours were positively associated with mortality from all-causes, CVD, and other causes in men and women.The sex- and age-stratified analyses did not reveal any major differences in the association between sleep duration and mortality outcomes in groups younger and older than 50 years of age. The only exception was the significant interaction between sleep duration and age in women for mortality from other causes.ConclusionsSleep durations ≥8 hours are associated with mortality outcomes in men and women. Age may be an effect modifier for the association between sleep duration and mortality from other causes in women.
KEYWORDS:
CVD mortality; Japan; all-cause mortality; cancer mortality; general population; sleep duration

The association between habitual sleep duration and mortality according to sex and age: the Japan Public Health Center-based Prospective Study.
Svensson T, Inoue M, Saito E, Sawada N, Iso H, Mizoue T, Goto A, Yamaji T, Shimazu T, Iwasaki M, Tsugane S.
J Epidemiol. 2020 Feb 1. doi: 10.2188/jea.JE20190210. [Epub ahead of print]
PMID: 32009104 Free Article
Abstract
BackgroundShort and long sleep durations are associated with mortality outcomes. The association between sleep duration and mortality outcomes may differ according to sex and age.MethodsParticipants of the Japan Public Health Center-based prospective study (JPHC Study) were aged 40-69 years and had completed a detailed questionnaire on lifestyle factors. Sex- and age-stratified analyses on the association between habitual sleep duration and mortality from all-causes, cardiovascular diseases (CVD), cancer and other causes included 46,152 men and 53,708 women without a history of CVD or cancer. Cox proportional hazards regression models, adjusted for potential confounders, were used to determine hazard ratios and 95% confidence intervals.ResultsMean follow-up time was 19.9 years for men and 21.0 years for women. In the multivariable sex-stratified models, and compared with 7 hours, some categories of sleep durations ≥ 8 hours were positively associated with mortality from all-causes, CVD, and other causes in men and women.The sex- and age-stratified analyses did not reveal any major differences in the association between sleep duration and mortality outcomes in groups younger and older than 50 years of age. The only exception was the significant interaction between sleep duration and age in women for mortality from other causes.ConclusionsSleep durations ≥8 hours are associated with mortality outcomes in men and women. Age may be an effect modifier for the association between sleep duration and mortality from other causes in women.
KEYWORDS:
CVD mortality; Japan; all-cause mortality; cancer mortality; general population; sleep duration

Cruciferous vegetables consumption and the risk of female lung cancer: a prospective study and a meta-analysis.
Wu QJ, Xie L, Zheng W, Vogtmann E, Li HL, Yang G, Ji BT, Gao YT, Shu XO, Xiang YB.
Ann Oncol. 2013 Jul;24(7):1918-1924. doi: 10.1093/annonc/mdt119. Epub 2019 Dec 4.
PMID: 32018634
Abstract
BACKGROUND:
Epidemiological studies evaluating the association between cruciferous vegetables (CVs) intake and female lung cancer risk have produced inconsistent results.
PATIENTS AND METHODS:
This study followed 74 914 Chinese women aged 40-70 years who participated in the Shanghai Women's Health Study. CV intake was assessed through a validated food-frequency questionnaire (FFQ) at baseline and reassessed during follow-up. Hazard ratios (HRs) and 95% confidence interval (CIs) were estimated by using Cox proportional hazards models. Furthermore, we carried out a meta-analysis of all observational studies until December 2011.
RESULTS:
After excluding the first 2 years of follow-up, 417 women developed lung cancer over a mean of 11.1 years of follow-up. An inverse association of borderline statistical significance was observed between CV consumption and female lung cancer risk, with HR for the highest compared with the lowest quartiles of 0.73 (95% CI 0.54-1.00, P trend = 0.1607). The association was strengthened in analyses restricting to never smokers, with the corresponding HR of 0.59 (95% CI 0.40-0.87, P trend = 0.0510). The finding of an inverse association between CV intake and lung cancer risk in women was supported by our meta-analysis of 10 included studies.
CONCLUSIONS:
Our study suggests that CV consumption may reduce the risk of lung cancer in women, particularly among never smokers.
KEYWORDS:
cruciferous vegetable; lung cancer; meta-analysis; prospective study; women

Dairy products and colorectal cancer risk: a systematic review and meta-analysis of cohort studies.
Aune D, Lau R, Chan DSM, Vieira R, Greenwood DC, Kampman E, Norat T.
Ann Oncol. 2012 Jan;23(1):37-45. doi: 10.1093/annonc/mdr269. Epub 2019 Dec 4.
PMID: 32018382
Abstract
BACKGROUND:
Previous studies of the association between intake of dairy products and colorectal cancer risk have indicated an inverse association with milk, however, the evidence for cheese or other dairy products is inconsistent.
METHODS:
We conducted a systematic review and meta-analysis to clarify the shape of the dose-response relationship between dairy products and colorectal cancer risk. We searched the PubMed database for prospective studies published up to May 2010. Summary relative risks (RRs) were estimated using a random effects model.
RESULTS:
Nineteen cohort studies were included. The summary RR was 0.83 (95% CI [confidence interval]: 0.78-0.88, I2 = 25%) per 400 g/day of total dairy products, 0.91 (95% CI: 0.85-0.94, I2 = 0%) per 200 g/day of milk intake and 0.96 (95% CI: 0.83-1.12, I2 = 28%) per 50 g/day of cheese. Inverse associations were observed in both men and women but were restricted to colon cancer. There was evidence of a nonlinear association between milk and total dairy products and colorectal cancer risk, P < 0.001, and the inverse associations appeared to be the strongest at the higher range of intake.
CONCLUSIONS:
This meta-analysis shows that milk and total dairy products, but not cheese or other dairy products, are associated with a reduction in colorectal cancer risk.
KEYWORDS:
colorectal cancer; dairy products; diet; meta-analysis

Konjac glucomannan polysaccharide and inulin oligosaccharide enhance the colonic mucosal barrier function and modulate gut-associated lymphoid tissue immunity in C57BL/6J mice.
Changchien CH, Han YC, Chen HL.
Br J Nutr. 2020 Feb 14;123(3):319-327. doi: 10.1017/S000711451900285X.
PMID: 31699162
Abstract
Both konjac glucomannan (KGM) and inulin oligosaccharide have been shown to improve bowel function, but their effects on the mucosal barrier function and immunity are not fully understood. The aim of the present study was to determine the effects of a low-level supplementation of dietary fibres on the colonic mucosal barrier function, antioxidant enzyme defence and immunity. C57BL/6J mice (6 weeks of age, eight per group) were randomly assigned to consume one of the following diets: control or control diet supplemented with 2 % (w/w) of KGM, inulin oligosaccharide (degree polymerisation = 😎 or KGM+inulin (1 %, w/w each (K+I)). Fresh faeces were collected on days 19-21. Mice were killed on day 22 after fasting. Segments of colon tissues were processed for histological procedure and stained for acidic mucins and tight junction protein marker zona occludin-1 (ZO-1). The remaining tissues were processed to determine the gene expression of mucin 2, tight junction proteins, antioxidant enzymes and cytokines. The plasma cytokines were measured. Results indicated that KGM, inulin and K+I significantly increased the mucosal layer thickness, mucin density (granule number/crypt) and gene expression of Muc2 as compared with the control. All fibre treatments increased the gene expressions of ZO-1, occludin, glutathione peroxidase, glutathione S-transferase π, catalase and IL-10. In addition, all fibre treatments increased faecal butyrate and probiotics, and plasma IL-10 concentrations. In conclusion, supplementation of low-level, 2 % (w/w), of K+I was sufficient to enhance the mucosal barrier function and anti-inflammatory status.
KEYWORDS:
Immunity; Inulin; Konjac glucomannan; Mucosal barrier; Tight junctions

Mobilization-based transplantation of young-donor hematopoietic stem cells extends lifespan in mice.
Guderyon MJ, Chen C, Bhattacharjee A, Ge G, Fernandez RA, Gelfond JAL, Gorena KM, Cheng CJ, Li Y, Nelson JF, Strong RJ, Hornsby PJ, Clark RA, Li S.
Aging Cell. 2020 Feb 3:e13110. doi: 10.1111/acel.13110. [Epub ahead of print]
PMID: 32012439
Abstract
Mammalian aging is associated with reduced tissue regeneration and loss of physiological integrity. With age, stem cells diminish in their ability to regenerate adult tissues, likely contributing to age-related morbidity. Thus, we replaced aged hematopoietic stem cells (HSCs) with young-donor HSCs using a novel mobilization-enabled hematopoietic stem cell transplantation (HSCT) technology as an alternative to the highly toxic conditioning regimens used in conventional HSCT. Using this approach, we are the first to report an increase in median lifespan (12%) and a decrease in overall mortality hazard (HR: 0.42, CI: 0.273-0.638) in aged mice following transplantation of young-donor HSCs. The increase in longevity was accompanied by reductions of frailty measures and increases in food intake and body weight of aged recipients. Young-donor HSCs not only preserved youthful function within the aged bone marrow stroma, but also at least partially ameliorated dysfunctional hematopoietic phenotypes of aged recipients. This compelling evidence that mammalian health and lifespan can be extended through stem cell therapy adds a new category to the very limited list of successful anti-aging/life-extending interventions. Our findings have implications for further development of stem cell therapies for increasing health and lifespan.
KEYWORDS:
Aging; age-associated health deficit; hematopoietic stem cell transplantation; longevity; mobilization-based conditioning; mouse

[AlPater]

Pan-mammalian analysis of molecular constraints underlying extended lifespan.
Kowalczyk A, Partha R, Clark NL, Chikina M.
Elife. 2020 Feb 11;9. pii: e51089. doi: 10.7554/eLife.51089.
PMID: 32043462
https://elifesciences.org/articles/51089
Abstract
Although lifespan in mammals varies over 100-fold, the precise evolutionary mechanisms underlying variation in longevity remain unknown. Species-specific genetic changes have been observed in long-lived species including the naked mole-rat, bats, and the bowhead whale, but these adaptations do not generalize to other mammals. We present a novel method to identify associations between rates of protein evolution and continuous phenotypes across the entire mammalian phylogeny. Unlike previous analyses that focused on individual species, we treat absolute and relative longevity as quantitative traits and demonstrate that these lifespan traits affect the evolutionary constraint on hundreds of genes. Specifically, we find that genes related to cell cycle, DNA repair, cell death, the IGF1 pathway, and immunity are under increased evolutionary constraint in large and long-lived mammals. For mammals exceptionally long-lived for their body size, we find increased constraint in inflammation, DNA repair, and NFKB-related pathways. Strikingly, these pathways have considerable overlap with those that have been previously reported to have potentially adaptive changes in single-species studies, and thus would be expected to show decreased constraint in our analysis. This unexpected finding of increased constraint in many longevity-associated pathways underscores the power of our quantitative approach to detect patterns that generalize across the mammalian phylogeny.
KEYWORDS:
RERconverge; computational biology; evolution; genetics; genomics; longevity; mammals; phylogenomics; systems biology

Nut Consumption and Risk of Cancer: A Meta-analysis of Prospective Studies.
Long J, Ji Z, Yuan P, Long T, Liu K, Li J, Cheng L.
Cancer Epidemiol Biomarkers Prev. 2020 Feb 10. doi: 10.1158/1055-9965.EPI-19-1167. [Epub ahead of print]
PMID: 32041895
Abstract
BACKGROUND:
Epidemiologic studies have investigated the association between nut intake and risk for multiple cancers. However, current findings are inconsistent and no definite conclusion has been drawn from prospective studies. We therefore conducted this meta-analysis to evaluate the relationship between nut consumption and risk of cancer.
METHODS:
Prospective studies reporting associations between nut intake and risk for all types of cancer were identified by searching Web of Science and PubMed databases up to June 2019. Risk ratios (RR) and 95% confidence intervals (CI) were extracted and then pooled across the studies using a random-effect model. A dose-response analysis was modeled by performing restricted cubic splines when data were available.
RESULTS:
Thirty-three studies that included more than 50,000 cancer cases were eligible for the analysis. When comparing the highest with the lowest category of nut intake, high consumption of nuts was significantly associated with decreased risk of overall cancer (RR = 0.90; 95% CI, 0.85-0.95). The protective effect of nut consumption was especially apparent against cancers from the digestive system (RR = 0.83; 95% CI, 0.77-0.89). Among different nut classes, significant association was only obtained for intake of tree nuts. We also observed a linear dose-response relationship between nut consumption and cancer: Per 20 g/day increase in nut consumption was related to a 10% (RR = 0.90; 95% CI, 0.82-0.99) decrease in cancer risk.
CONCLUSIONS:
Our analysis demonstrated an inverse association of dietary nut consumption with cancer risk, especially for cancers from the digestive system.
IMPACT:
This study highlights the protective effect of nuts against cancer.

Alcohol consumption in later life and reaching longevity: the Netherlands Cohort Study.
van den Brandt PA, Brandts L.
Age Ageing. 2020 Feb 9. pii: afaa003. doi: 10.1093/ageing/afaa003. [Epub ahead of print]
PMID: 32037449
https://watermark.silverchair.com/afaa003.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAnowggJ2BgkqhkiG9w0BBwagggJnMIICYwIBADCCAlwGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMNXNpsMbgK2ntdnUUAgEQgIICLfPkuil8MaHYwyiZHxqYvI_2qMk-jvBvJuRjAOC6bNKO1vJZBjoawr6epVitkYqQsBXo53KCwsX9mz_tmOX6cnHiuBMyLeTjwMm3t_rxwwNft5fDXOX7R0ayuenOk0rG1Bpyz3JfIMIrDapNyPNw_qPySPKED6Xu0ec8o2FWywy_XxEWFP8qQtaWLPfdxW9bVeoujeuhdoJVN4Kvg1rsdFntbSLAR3k4XKwpBESdsIFZYUBa4jJgW5ZNdKZftR7MhTIEyTleTzR78esC1oudwrmA_Jy6tOhHAll0Gq508JYx3NY-rZR305IlVsjqHXl3M08KMPwVmfgmbuqPYMSZRuys7CjemkrCZhKEyTYTEWdUklsguiOVPa7UlHnoam1kl6Duor1x36INBb9VmUF208rzA4nygTFszjpj8fc2Qoky8naKf0BhOJ9EcfGwv-SFmPocH_MmXF-MYaJT4J9TPqRt8xiSwMj0pnufpnxRImFKQP0T2zSOaJYlc5pq9zwT0sx72PPJG2l7Srta3wzQ9pB7S6V9eU3NaLuyswhkW3LbjWmjajHNqXBO5HdVNMOlLExMhywe2Wd-eJYjbe2GkQe06oQVzJEvgpEdniSHuaBUShuu_Mtu-dXnMgazp1Bbk5-2dwGZZ-5Ml-rBcH5tN3funDKSWVl5qNQU7MCNA2XEJyeyIeuJxPp1BvdG_9O6AtMpt4DVHkc8FPhBnJJdVxQXilp8tSgPJdHzvlWs
Abstract
BACKGROUND:
whether light-to-moderate alcohol intake is related to reduced mortality remains a subject of intense research and controversy. There are very few studies available on alcohol and reaching longevity.
METHODS:
we investigated the relationship of alcohol drinking characteristics with the probability to reach 90 years of age. Analyses were conducted using data from the Netherlands Cohort Study. Participants born in 1916-1917 (n = 7,807) completed a questionnaire in 1986 (age 68-70 years) and were followed up for vital status until the age of 90 years (2006-07). Multivariable Cox regression analyses with fixed follow-up time were based on 5,479 participants with complete data to calculate risk ratios (RRs) of reaching longevity (age 90 years).
RESULTS:
we found statistically significant positive associations between baseline alcohol intake and the probability of reaching 90 years in both men and women. Overall, the highest probability of reaching 90 was found in those consuming 5- < 15 g/d alcohol, with RR = 1.36 (95% CI, 1.20-1.55) when compared with abstainers. The exposure-response relationship was significantly non-linear in women, but not in men. Wine intake was positively associated with longevity (notably in women), whereas liquor was positively associated with longevity in men and inversely in women. Binge drinking pointed towards an inverse relationship with longevity. Alcohol intake was associated with longevity in those without and with a history of selected diseases.
CONCLUSIONS:
the highest probability of reaching 90 years was found for those drinking 5- < 15 g alcohol/day. Although not significant, the risk estimates also indicate to avoid binge drinking.
KEYWORDS:
aging; alcohol; cohort studies; dose–response relationship; longevity; mortality; older people

[AlPater]

Long-term effects of alcohol consumption on cognitive function: a systematic review and dose-response analysis of evidence published between 2007 and 2018.
Brennan SE, McDonald S, Page MJ, Reid J, Ward S, Forbes AB, McKenzie JE.
Syst Rev. 2020 Feb 13;9(1):33. doi: 10.1186/s13643-019-1220-4.
PMID: 32054517
Abstract
BACKGROUND:
Understanding the long-term health effects of low to moderate alcohol consumption is important for establishing thresholds for minimising the lifetime risk of harm. Recent research has elucidated the dose-response relationship between alcohol and cardiovascular outcomes, showing an increased risk of harm at levels of intake previously thought to be protective. The primary objective of this review was to examine (1) whether there is a dose-response relationship between levels of alcohol consumption and long-term cognitive effects, and (2) what the effects are of different levels of consumption.
METHODS:
The review was conducted according to a pre-specified protocol. Eligible studies were those published 2007 onwards that compared cognitive function among people with different levels of alcohol consumption (measured ≥ 6 months prior to first follow-up of cognition). Major cognitive impairment was excluded. Searches were limited to MEDLINE, Embase and PsycINFO (January 2007 to April 2018). Screening, data extraction, and risk of bias assessment (ROBINS-I) were piloted by three authors, then completed by a single author and checked by a second. Analyses were undertaken to identify and characterise dose-response relationships between levels of alcohol consumption and cognition. Certainty of evidence was assessed using GRADE.
RESULTS:
We included 27 cohort studies (from 4786 citations). Eighteen studies examined the effects of alcohol consumption at different levels (risk of bias 16 serious, 2 critical). Ten studies provided data for dose-response analysis. The pooled dose-response relationship showed a maximum standardised mean difference (SMD) indicating slightly better cognition among women with moderate alcohol consumption compared to current non-drinkers (SMD 0.18, 95%CI 0.02 to 0.34, at 14.4 grams/day; 5 studies, very low certainty evidence), and a trivial difference for men (SMD 0.05, 95% CI 0.00 to 0.10, at 19.4 grams/day; 6 studies, very low certainty evidence).
CONCLUSIONS:
Major limitations in the design and reporting of included studies made it impossible to discern if the effects of 'lower' levels of alcohol intake are due to bias. Further review of the evidence is unlikely to resolve this issue without meta-analysis of individual patient data from cohort studies that address biases in the selection of participants and classification of alcohol consumption.
KEYWORDS:
Alcohol; Cognition dose-response; Meta-analysis; Systematic review

A circadian rhythm-related MTNR1B genetic variant (rs10830963) modulate body weight change and insulin resistance after 9 months of a high protein/low carbohydrate vs a standard hypocaloric diet.
de Luis DA, Izaola O, Primo D, Aller R.
J Diabetes Complications. 2020 Jan 13:107534. doi: 10.1016/j.jdiacomp.2020.107534. [Epub ahead of print]
PMID: 32057567
Abstract
BACKGROUND & AIMS:
The risk allele (G) of rs10830963 in the melatonin receptor 1 B (MTNR1B) gene presents an association with biochemical parameters and obesity. We study the effect of this SNP on insulin resistance and weight loss secondary to two hypocaloric diets.
METHODS:
270 obese subjects were randomly allocated during 9 months (Diet HP: a high protein/low carbohydrate vs. Diet S: a standard severe hypocaloric diets). Anthropometric parameters, fasting blood glucose, C-reactive protein (CRP), insulin concentration, insulin resistance (HOMA-IR), lipid profile and adipocytokines levels were measured. Genotype of MTNR1B gene polymorphism (rs10830963) was evaluated.
RESULTS:
All adiposity parameters, systolic blood pressure and leptin levels decreased in all subjects after both diets. This improvement of adiposity parameters was higher in non-G allele carriers than G allele carriers. After weight loss with Diet HP, (CC vs. CG + GG at 9 months); total cholesterol (delta: -9.9 ± 2.4 mg/dl vs. -4.8 ± 2.2 mg/dl:p < 0.05), LDL-cholesterol (delta: -8.3 ± 1.9 mg/dl vs. -5.1 ± 2.2 mg/dl: p < 0.05), insulin (delta: -4.7 ± 0.8 UI/L vs. -0.9 ± 1.0 UI/L: p < 0.05), triglycerides (delta: -17.7 ± 3.9 mg/dl vs. -6.1 ± 2.8 mg/dl: p < 0.05) and HOMA IR (delta: -0.8 ± 0.2 units vs. -0.2 ± 0.1 units: p < 0.05) improved only in no G allele carriers. After weight loss with Diet S in non G allele carriers, insulin levels (delta (CC vs. CG + GG): -3.4 ± 0.6 UI/L vs. -1.2 ± 0.4 UI/L: p < 0.05), triglycerides (delta: -29.2 ± 3.4 mg/dl vs. -8.2 ± 3.8 mg/dl: p < 0.05), HOMA-IR (delta (CC vs. CG + GG): -1.1 ± 0.2 units vs. -0.1 ± 0.1 units: p < 0.05), total cholesterol (delta: -15.9 ± 7.4 mg/dl vs. -5.8 ± 2.9 mg/dl:ns) and LDL-cholesterol (delta: -13.7 ± 5.9 mg/dl vs. -6.0 ± 2.9 mg/dl: ns) decreased, too.
CONCLUSIONS:
our study detected a relationship of rs10830963 variant of MTNR1B gene with adiposity changes, cholesterol changes and insulin resistance modification induced by two different hypocaloric during 9 months.
KEYWORDS:
High protein diet; MTNR1B; Standard diet; rs10830963

Eating and healthy ageing: a longitudinal study on the association between food consumption, memory loss and its comorbidities.
Xu X, Ling M, Inglis SC, Hickman L, Parker D.
Int J Public Health. 2020 Feb 12. doi: 10.1007/s00038-020-01337-y. [Epub ahead of print]
PMID: 32052084
https://sci-hub.tw/https://link.springer.com/article/10.1007/s00038-020-01337-y
Abstract
OBJECTIVES:
To explore the longitudinal association between food groups and memory loss and comorbid heart disease and diabetes (both Type 1 and 2) for people living in New South Wales, Australia.
METHODS:
We assessed 139,096 adults (aged 45 years and over) from the 45 and Up Study who completed both baseline (2006-2009) and follow-up (2012-2015) surveys. Mixed linear and generalized estimating equation models were used to examine the longitudinal associations.
RESULTS:
High consumption of fruit, vegetable and protein-rich food associated with lower odds of memory loss. High consumption of fruit and vegetables also associated with lower odds of comorbid heart disease (p ≤ 0.001). People who aged ≥ 80 years with low consumption of cereals had the highest odds of memory loss and comorbid heart disease than people in other age groups (p < 0.01).
CONCLUSIONS:
The results highlighted the longitudinal association of fruit and vegetable in relation to memory loss and comorbid heart disease. Age effects on cereals consumption which have an influence on memory loss and comorbid heart disease.
KEYWORDS:
Comorbidities; Food groups; Heart disease; Longitudinal study; Memory loss

Relationship between Inflammatory Food Consumption and Age-Related Hearing Loss in a Prospective Observational Cohort: Results from the Salus in Apulia Study.
Sardone R, Lampignano L, Guerra V, Zupo R, Donghia R, Castellana F, Battista P, Bortone I, Procino F, Castellana M, Passantino A, Rucco R, Lozupone M, Seripa D, Panza F, De Pergola G, Giannelli G, Logroscino G, Boeing H, Quaranta N.
Nutrients. 2020 Feb 7;12(2). pii: E426. doi: 10.3390/nu12020426.
PMID: 32046004
Abstract
Age related hearing loss (ARHL) affects about one third of the elderly population. It is suggested that the senescence of the hair cells could be modulated by inflammation. Thus, intake of anti- and pro-inflammatory foods is of high interest.
METHODS:
From the MICOL study population, 734 participants were selected that participated in the 2013 to 2018 examination including hearing ability and from which past data collected in 2005/2008 was available. ARHL status was determined and compared cross-sectionally and retrospectively according to clinical and lifestyle data including food and micronutrient intake.
RESULTS:
ARHL status was associated with higher age but not with education, smoking, relative weight (BMI), and clinical-chemical blood markers in the crossectional and retrospective analyses. Higher intake of fruit juices among ARHL-participants was seen cross-sectionally, and of sugary foods, high-caloric drinks, beer, and spirits retrospectively. No difference was found for the other 26 food groups and for dietary micronutrients with the exception of past vitamin A, which was higher among normal hearing subjects.
CONCLUSIONS:
Pro-inflammatory foods with a high-sugar content and also beer and spirits were found to be assocated with positive ARHL-status, but not anti-inflammatory foods. Diet could be a candidate for lifestyle advice for the prevention of ARHL.
KEYWORDS:
age-related hearing loss; alcohol; diet; food; inflammation; population studies; presbycusis; sugar

Low-energy total diet replacement intervention in patients with type 2 diabetes mellitus and obesity treated with insulin: a randomized trial.
Brown A, Dornhorst A, McGowan B, Omar O, Leeds AR, Taheri S, Frost GS.
BMJ Open Diabetes Res Care. 2020 Jan;8(1). pii: e001012. doi: 10.1136/bmjdrc-2019-001012.
PMID: 32049634
https://drc.bmj.com/content/bmjdrc/8/1/e001012.full.pdf
Abstract
OBJECTIVES:
The management of patients with long-standing type 2 diabetes and obesity receiving insulin therapy (IT) is a substantial clinical challenge. Our objective was to examine the effect of a low-energy total diet replacement (TDR) intervention versus standardized dietetic care in patients with long-standing type 2 diabetes and obesity receiving IT.
RESEARCH DESIGN AND METHODS:
In a prospective randomized controlled trial, 90 participants with type 2 diabetes and obesity receiving IT were assigned to either a low-energy TDR (intervention) or standardized dietetic care (control) in an outpatient setting. The primary outcome was weight loss at 12 months with secondary outcomes including glycemic control, insulin burden and quality of life (QoL).
RESULTS:
Mean weight loss at 12 months was 9.8 kg (SD 4.9) in the intervention and 5.6 kg (SD 6.1) in the control group (adjusted mean difference -4.3 kg, 95% CI -6.3 to 2.3, p<0.001). IT was discontinued in 39.4% of the intervention group compared with 5.6% of the control group among completers. Insulin requirements fell by 47.3 units (SD 36.4) in the intervention compared with 33.3 units (SD 52.9) in the control (-18.6 units, 95% CI -29.2 to -7.9, p=0.001). Glycated Hemoglobin (HbA1c) fell significantly in the intervention group (4.7 mmol/mol; p=0.02). QoL improved in the intervention group of 11.1 points (SD 21.8) compared with 0.71 points (SD 19.4) in the control (8.6 points, 95% CI 2.0 to 15.2, p=0.01).
CONCLUSIONS:
Patients with advanced type 2 diabetes and obesity receiving IT achieved greater weight loss using a TDR intervention while also reducing or stopping IT and improving glycemic control and QoL. The TDR approach is a safe treatment option in this challenging patient group but requires maintenance support for long-term success.
KEYWORDS:
insulin; low calorie diet; obesity; type 2 diabetes

[AlPater]

Protein Type, Protein Dose, and Age Modulate Dietary Protein Digestion and Phenylalanine Absorption Kinetics and Plasma Phenylalanine Availability in Humans.
Gorissen SHM, Trommelen J, Kouw IWK, Holwerda AM, Pennings B, Groen BBL, Wall BT, Churchward-Venne TA, Horstman AMH, Koopman R, Burd NA, Fuchs CJ, Dirks ML, Res PT, Senden JMG, Steijns JMJM, de Groot LCPGM, Verdijk LB, van Loon LJC.
J Nutr. 2020 Feb 18. pii: nxaa024. doi: 10.1093/jn/nxaa024. [Epub ahead of print]
PMID: 32069356
Abstract
BACKGROUND:
Dietary protein ingestion stimulates muscle protein synthesis by providing amino acids to the muscle. The magnitude and duration of the postprandial increase in muscle protein synthesis rates are largely determined by dietary protein digestion and amino acid absorption kinetics.
OBJECTIVE:
We assessed the impact of protein type, protein dose, and age on dietary protein digestion and amino acid absorption kinetics in vivo in humans.
METHODS:
We included data from 18 randomized controlled trials with a total of 602 participants [age: 53 ± 23 y; BMI (kg/m2): 24.8 ± 3.3] who consumed various quantities of intrinsically l-[1-13C]-phenylalanine-labeled whey (n = 137), casein (n = 393), or milk (n = 72) protein and received intravenous infusions of l-[ring-2H5]-phenylalanine, which allowed us to assess protein digestion and phenylalanine absorption kinetics and the postprandial release of dietary protein-derived phenylalanine into the circulation. The effect of aging on these processes was assessed in a subset of 82 young (aged 22 ± 3 y) and 83 older (aged 71 ± 5 y) individuals.
RESULTS:
A total of 50% ± 14% of dietary protein-derived phenylalanine appeared in the circulation over a 5-h postprandial period. Casein ingestion resulted in a smaller (45% ± 11%), whey protein ingestion in an intermediate (57% ± 10%), and milk protein ingestion in a greater (65% ± 13%) fraction of dietary protein-derived phenylalanine appearing in the circulation (P < 0.001). The postprandial availability of dietary protein-derived phenylalanine in the circulation increased with the ingestion of greater protein doses (P < 0.05). Protein digestion and phenylalanine absorption kinetics were attenuated in older when compared with young individuals, with 45% ± 10% vs. 51% ± 14% of dietary protein-derived phenylalanine appearing in the circulation, respectively (P = 0.001).
CONCLUSIONS:
Protein type, protein dose, and age modulate dietary protein digestion and amino acid absorption kinetics and subsequent postprandial plasma amino acid availability in vivo in humans.
KEYWORDS:
healthy aging; muscle mass maintenance; muscle protein synthesis; sarcopenia; splanchnic extraction

The effect of psyllium supplementation on blood pressure: a systematic review and meta-analysis of randomized controlled trials.
Clark CCT, Salek M, Aghabagheri E, Jafarnejad S.
Korean J Intern Med. 2020 Feb 19. doi: 10.3904/kjim.2019.049. [Epub ahead of print]
PMID: 32066221
Abstract
BACKGROUND/AIMS:
Global incidence of hypertension is estimated to be, in excess of, one billion people, and given the efficacy of soluble dietary fibers, in particular, Psyllium, to positively impact blood pressure in patients with hypertension, it is of clinical importance that consensus on its supplementation be established. Therefore, the aim of the study was systematically review and meta-analyze the effect of psyllium supplementation on blood pressure of hypertensive patients in randomized controlled trials.
METHODS:
We searched six universal databases including; Pubmed/Medline, Ovid, Cochrane Library, Google Scholar, Embase, and Scopus until November 2018. Both combined and stratified analyzes were conducted. A fixed-effects or random- effects model was used to assess the mean effect sizes.
RESULTS:
An eventual 11 trials with 592 participants were considered as eligible for inclusion in the present meta-analysis. The meta-analysis revealed a significant reduction of 2.04 mmHg in systolic blood pressure (weighted mean difference, -2.04; 95% confidence interval, -2.82 to -1.63; p < 0.001). Whilst meta-regression highlighted that the hypotensive effect of psyllium was stronger in subjects with higher baseline blood pressure.
CONCLUSIONS:
Given the overarching benefits and lack of reported side effects, particularly for hypertensive patients, health care providers and clinicians should consider the use of psyllium supplementation for the treatment or abatement of hypertension, or hypertensive symptoms.
KEYWORDS:
Blood pressure; Dietary fiber; Meta-analysis; Psyllium

Risk factors for primary lung cancer among never-smoking women in South Korea: a retrospective nationwide population-based cohort study.
Ko YH, Kim SJ, Kim WS, Park CK, Park CK, Suh YG, Eom JS, Cho S, Hur JY, Hwang SH, Myong JP.
Korean J Intern Med. 2020 Feb 19. doi: 10.3904/kjim.2019.283. [Epub ahead of print]
PMID: 32066220
Abstract
BACKGROUND/AIMS:
We performed a large-scale, retrospective, nationwide, cohort study to investigate the risk factors for lung cancer among never-smoking Korean females.
METHODS:
The study data were collected from a general health examination and questionnaire survey of eligible populations conducted between January 1, 2003 and December 31, 2004; the data were acquired from the tailored big data distribution service of the National Health Insurance Service. After a 1-year clearance period, 5,860,922 of 6,318,878 never-smoking female participants with no previous history of lung cancer were investigated. After a median follow-up of 11.4 years, 43,473 (0.74%) participants were defined as "newly diagnosed lung cancer".
RESULTS:
After adjusting for all variables at baseline, the variables older age, lower body mass index (BMI), less exercise, frequent alcohol drinking, meat-based diet, rural residence, and previous history of cancer were associated with a higher incidence of lung cancer. Low BMI (< 18.5 kg/m2: hazard ratio, 1.33; 95% confidence interval [CI], 1.27 to 1.40) was a significant independent risk factor; as BMI decreased, HR increased. Negative associations between BMI and lung-cancer development were also observed after controlling for age (p for trend < 0.001). Drinking alcohol one to two times a week (HR, 1.25; 95% CI, 1.21 to 1.28) and eating a meat-based diet (HR, 1.08; 95% CI, 1.01 to 1.15) were associated with lung-cancer incidence.
CONCLUSIONS:
Modifiable baseline characteristics, such as BMI, exercise, alcohol consumption, and diet, are risk factors for lung-cancer development among never- smoking females. Thus, lifestyle modifications may help prevent lung cancer.
KEYWORDS:
Cohort studies; Lung neoplasm; Never-smoking women; Risk factor

Association between saturated fatty acid intake and depressive symptoms in midlife women: A prospective study.
Li D, Liang H, Tong Y, Zheng H, Li Y.
J Affect Disord. 2020 Jan 29;267:17-22. doi: 10.1016/j.jad.2020.01.173. [Epub ahead of print]
PMID: 32063568
Abstract
BACKGROUND:
This prospective investigation examined relations between baseline dietary saturated fatty acid (SFA) intake of women at midlife and prevalence of depressive symptoms 4 years later.
METHODS:
Women enrolled in the Study of Women's Health Across the Nation (SWAN) had measures of CES-D depression scores 4 years later and SFA intake at baseline. Logistic regression models were used to study prospective associations between SFA intake and depressive symptoms.
RESULTS:
A total of 2400 women aged 42-52 years were included in the present study. The ORs of depressive symptoms in model 1 adjustment for baseline CES-D score indicated that baseline SFA intake was positively associated with depressive symptoms. After additional adjustment for age, race/ethnicity, education, financial strain, physical activity, smoking currently, BMI, menopausal status, VMS, chronic stress and use of antidepressant in model 2, the results were similar to those of the model 1. This association remained statistically significant and changed little when additional controlling for SHBG and FSH in fully adjusted model 3. The fully adjusted OR of depressive symptoms in model 3 was 2.423 (1.142-5.143) in quartile 4 (the highest) versus quartile 1 (the lowest) of the baseline SFA intake.
LIMITATIONS:
Assessment of depression and SFA intake was based on a self-report scale.
CONCLUSIONS:
Baseline SFA intake is a predictor for depressive symptoms assessed 4 years later in midlife women. This underlines the importance of targeting SFA intake in the prevention of major depression in midlife women.
KEYWORDS:
Depressive symptoms; Epidemiology; Midlife women; Prospective; Saturated fatty acid

[Frequency of bowel movements and risk of Parkinson's disease: a prospective cohort study in adults in China].
Yang SC, Fan MY, Yu CQ, Guo Y, Bian Z, Pei P, Chen JS, Chen ZM, Lyu J, Li LM; China Kadoorie Biobank Collaborative Group.
Zhonghua Liu Xing Bing Xue Za Zhi. 2020 Jan 10;41(1):48-54. doi: 10.3760/cma.j.issn.0254-6450.2020.01.010. Chinese.
PMID: 32062942
Abstract
Objective: To evaluate the association between the frequency of bowel movement (BMF) and the risk of Parkinson's disease (PD). Methods: In this study, 510 134 participants from the China Kadoorie Biobank (CKB) were included after excluding those who reported to had been diagnosed with cancer at baseline survey. The baseline survey was conducted from 2004 to 2008. The study used the data from the baseline survey and follow-up until December 31, 2016. Cox proportional hazards regression models were used to estimate the HRs and the 95%CIs of risk of PD diagnosis with BMF. Results: During an average follow-up period of (9.9±1.9) years, 808 participants were diagnosed with PD. Compared with participants who had bowel movements every day, the multivariable-adjusted HR (95%CI) for those who had bowel movements<3 times/week, once every 2-3 days, and>1 time/day were 3.62 (2.88-4.54), 2.13 (1.74-2.60), and 0.81 (0.63-1.05), respectively. The linear trend test results of the association between BMF and risk of PD diagnosis was significant (P<0.001). Compared with the participants who had bowel movements ≥1 time/day, the multivariable-adjusted HR (95%CI) for those who had bowel movements<1 time/day was 3.13 (2.32-4.23) within the 5 years of follow- up and was 2.48 (2.05-3.01) beyond the 5 years of follow-up. The gender specific results were similar. The association of BMF<1 time/day with risk of PD diagnosis was stronger in older participants. Conclusions: The participants with low BMF at baseline survey would have higher risk for PD diagnosis in the subsequent 10 years on average. Since abnormal decrease of BMF is easy to be found, programs could be set up for the early screening of PD in older people, along with other early symptoms of PD.
KEYWORDS:
Cohort studies; Defecation; Parkinson disease

Dose-Response Relationships Between Body Composition Indices and All-Cause Mortality in Older Japanese Adults.
Seino S, Kitamura A, Abe T, Taniguchi Y, Yokoyama Y, Amano H, Nishi M, Nofuji Y, Narita M, Ikeuchi T, Fujiwara Y, Shinkai S.
J Am Med Dir Assoc. 2020 Feb 14. pii: S1525-8610(19)30827-8. doi: 10.1016/j.jamda.2019.11.018. [Epub ahead of print]
PMID: 32067890
https://sci-hub.tw/10.1016/j.jamda.2019.11.018
Abstract
OBJECTIVES:
We examined the dose-response relationships of body composition indices with mortality and identified the best predictor.
DESIGN AND SETTING:
Kusatsu Longitudinal Study and Hatoyama Cohort Study, Japan.
PARTICIPANTS:
In total, 1977 community-dwelling Japanese adults age ≥65 years (966 men and 1011 women) participated.
MEASUREMENTS:
Body mass index (BMI), fat mass index (FMI), fat-free mass index (FFMI), and skeletal muscle mass index (SMI) were determined by segmental multifrequency bioelectrical impedance analysis. The main outcome was all-cause mortality. We determined multivariate-adjusted hazard ratios for mortality relative to sex-specific medians of each body composition index and examined the association shapes.
RESULTS:
During the median follow-up of 5.3 years, 128 (13.3%) men and 75 (7.4%) women died. Compared with median BMIs (23.3 kg/m2 in men and 22.8 kg/m2 in women), a BMI >23.3 and ≤26.1 kg/m2 was associated with significantly lower mortality risk in men, and a BMI <22.8 kg/m2 was associated with significantly higher mortality risk in women. The inverse dose-response relationship with mortality was clearer for FFMI [hazard ratios (95% confidence interval) of 10th and 90th percentiles: 1.58 (1.23-2.03) and 0.58 (0.44-0.79), respectively, in men and 1.56 (1.12-2.16) and 0.68 (0.51-0.91), respectively, in women] and SMI [1.57 (1.22-2.01) and 0.60 (0.45-0.80), respectively, in men and 1.45 (1.05-2.01) and 0.77 (0.61-0.96), respectively, in women] than for BMI [1.30 (0.92-1.83) and 0.65 (0.41-1.03), respectively, in men and 1.87 (1.18-2.95) and 0.88 (0.54-1.42), respectively, in women]. FMI was not associated with mortality in either sex.
CONCLUSIONS AND IMPLICATIONS:
FFMI and SMI were more definitive predictors of mortality than were BMI and FMI. The lower mortality risk with higher FFMI, regardless of FMI, may explain the age-related weakening of the association between higher BMI and mortality (the "obesity paradox"). FFMI and SMI evaluation should be introduced to clinical assessments of older adults because mortality risk might be reduced by maintaining muscle mass.
KEYWORDS:
Body composition; body mass index; fat mass; fat-free mass; mortality; muscle mass

Dietary creatine intake and depression risk among U.S. adults.
Bakian AV, Huber RS, Scholl L, Renshaw PF, Kondo D.
Transl Psychiatry. 2020 Feb 3;10(1):52. doi: 10.1038/s41398-020-0741-x.
PMID: 32066709
https://www.nature.com/articles/s41398-020-0741-x.pdf
Abstract
Creatine monohydrate is actively being researched for its antidepressant effects, yet little is known about the link between dietary creatine and depression risk. This study examines the association between dietary creatine and depression in U.S. adults, using data from the 2005 to 2012 National Health and Nutrition Examination Survey (NHANES). Patient health questionnaire, dietary creatine intake and covariates were obtained on 22,692 NHANES participants ≥20 years of age. Depression prevalence was calculated within quartiles of dietary creatine intake. Adjusted logistic regression models were formulated to determine the relationship between dietary creatine intake and depression risk. Additional covariates included income to poverty ratio, race/ethnicity, sex, age, education level, body mass index, healthcare access, smoking status, physical activity, and antidepressant/anxiolytic medication use. Models were further stratified by sex, age group, and antidepressant/anxiolytic medication use. Depression prevalence was 10.23/100 persons (95% CI: 8.64-11.83) among NHANES participants in the lowest quartile of dietary creatine intake compared with 5.98/100 persons (95% CI: 4.97-6.98) among participants in the highest quartile (p < 0.001). An inverse association was measured between dietary creatine and depression (adjusted odds ratio (AOR) = 0.68, 95% CI: 0.52-0.88). Dietary creatine's negative association with depression was strongest in females (AOR = 0.62, 95% CI: 0.40-0.98), participants aged 20-39 years (AOR = 0.52, 95% CI: 0.34-0.79) and participants not taking antidepressant/anxiolytic medication (AOR = 0.58, 95% CI: 0.43-0.77). Study results indicate a significant negative relationship between dietary creatine and depression in a nationally representative adult cohort. Further research is warranted to investigate the role creatine plays in depression, particularly among women and across the lifespan.

Effect of Low-Dose Vitamin K2 Supplementation on Bone Mineral Density in Middle-Aged and Elderly Chinese: A Randomized Controlled Study.
Zhang Y, Liu Z, Duan L, Ji Y, Yang S, Zhang Y, Li H, Wang Y, Wang P, Chen J, Li Y.
Calcif Tissue Int. 2020 Feb 14. doi: 10.1007/s00223-020-00669-4. [Epub ahead of print]
PMID: 32060566
https://sci-hub.tw/10.1007/s00223-020-00669-4
Abstract
Previous studies indicated a positive effect of vitamin K2 (VK2) supplementation on bone turnover biomarkers and bone mineral density (BMD), but the doses varied, and few studies have focused on the difference between VK2 supplementation alone and in combination with calcium and vitamin D3. The aim of this study was to explore a low and effective dose of VK2 for improving BMD, and to examine whether the co-supplementation of VK2, calcium and vitamin D3 would bring greater effects. In this trial, a total of 311 community-dwelling men and postmenopausal women aged 50 and 75 years were randomly assigned to four groups, receiving placebo, 50 µg/day, 90 µg/day or co-supplementation with calcium (500 mg/day) and vitamin D3 (10 µg/day) for 1 year. At the endpoint, the bone loss of femoral neck was significantly lower in postmenopausal women in the two 90 µg groups (treatment × time, p = 0.006) compared with placebo, but no effects in men. Serum biomarkers cOC/ucOC ratio increased in the intervention groups (treatment × time, p < 0.001). VK2 supplementation in dose of 90 µg/day performed a significant effect on reducing bone loss in postmenopausal women, but in combination with calcium and vitamin D3 brought no additional effects.Trial registration This trial was registered at http://www.chictr.org.cn as chiCTR1800019240.
KEYWORDS:
Bone mineral density; Menaquinone-7; Osteoporosis; Postmenopausal women; Vitamin K2

Edited February 19, 2020 by AlPater

[AlPater]

Dietary protein intake and all-cause and cause-specific mortality: results from the Rotterdam Study and a meta-analysis of prospective cohort studies.
Chen Z, Glisic M, Song M, Aliahmad HA, Zhang X, Moumdjian AC, Gonzalez-Jaramillo V, van der Schaft N, Bramer WM, Ikram MA, Voortman T.
Eur J Epidemiol. 2020 Feb 19. doi: 10.1007/s10654-020-00607-6. [Epub ahead of print]
PMID: 32076944
https://link.springer.com/content/pdf/10.1007/s10654-020-00607-6.pdf
Abstract
Evidence for associations between long-term protein intake with mortality is not consistent. We aimed to examine associations of dietary protein from different sources with all-cause and cause-specific mortality. We followed 7786 participants from three sub-cohorts of the Rotterdam Study, a population-based cohort in the Netherlands. Dietary data were collected using food-frequency questionnaires at baseline (1989-1993, 2000-2001, 2006-2008). Deaths were followed until 2018. Associations were examined using Cox regression. Additionally, we performed a highest versus lowest meta-analysis and a dose-response meta-analysis to summarize results from the Rotterdam Study and previous prospective cohorts. During a median follow-up of 13.0 years, 3589 deaths were documented in the Rotterdam Study. In this cohort, after multivariable adjustment, higher total protein intake was associated with higher all-cause mortality [e.g. highest versus lowest quartile of total protein intake as percentage of energy (Q4 versus Q1), HR = 1.12 (1.01, 1.25)]; mainly explained by higher animal protein intake and CVD mortality [Q4 versus Q1, CVD mortality: 1.28 (1.03, 1.60)]. The association of animal protein intake and CVD was mainly contributed to by protein from meat and dairy. Total plant protein intake was not associated with all-cause or cause-specific mortality, mainly explained by null associations for protein from grains and potatoes; but higher intake of protein from legumes, nuts, vegetables, and fruits was associated with lower risk of all-cause and cause-specific mortality. Findings for total and animal protein intake were corroborated in a meta-analysis of eleven prospective cohort studies including the Rotterdam Study (total 64,306 deaths among 350,452 participants): higher total protein intake was associated with higher all-cause mortality [pooled RR for highest versus lowest quantile 1.05 (1.01, 1.10)]; and for dose-response per 5 energy percent (E%) increment, 1.02 (1.004, 1.04); again mainly driven by an association between animal protein and CVD mortality [highest versus lowest, 1.09 (1.01, 1.18); per 5 E% increment, 1.05 (1.02, 1.09)]. Furthermore, in the meta-analysis a higher plant protein intake was associated with lower all-cause and CVD mortality [e.g. for all-cause mortality, highest versus lowest, 0.93 (0.87, 0.99); per 5 E% increment, 0.87 (0.78, 0.98), for CVD mortality, highest versus lowest 0.86 (0.73, 1.00)]. Evidence from prospective cohort studies to date suggests that total protein intake is positively associated with all-cause mortality, mainly driven by a harmful association of animal protein with CVD mortality. Plant protein intake is inversely associated with all-cause and CVD mortality. Our findings support current dietary recommendations to increase intake of plant protein in place of animal protein.
KEYWORDS:
All-cause mortality; Cardiovascular mortality; Cause-specific mortality; Cohort study; Dietary protein intake

A Novel Micronutrient Blend Mimics Calorie Restriction Transcriptomics in Multiple Tissues of Mice and Increases Lifespan and Mobility in C. elegans.
Serna E, Mastaloudis A, Martorell P, Wood SM, Hester SN, Bartlett M, Prolla TA, Viña J.
Nutrients. 2020 Feb 14;12(2). pii: E486. doi: 10.3390/nu12020486.
PMID: 32075050
Abstract
BACKGROUND:
We previously described a novel micronutrient blend that behaves like a putative calorie restriction mimetic. The aim of this paper was to analyze the beneficial effects of our micronutrient blend in mice and C. elegans, and compare them with calorie restriction.
METHODS:
Whole transcriptomic analysis was performed in the brain cortex, skeletal muscle and heart in three groups of mice: old controls (30 months), old + calorie restriction and old + novel micronutrient blend. Longevity and vitality were tested in C. elegans.
RESULTS:
The micronutrient blend elicited transcriptomic changes in a manner similar to those in the calorie-restricted group and different from those in the control group. Subgroup analysis revealed that nuclear hormone receptor, proteasome complex and angiotensinogen genes, all of which are known to be directly related to aging, were the most affected. Furthermore, a functional analysis in C. elegans was used. We found that feeding C. elegans the micronutrient blend increased longevity as well as vitality.
CONCLUSIONS:
We describe a micronutrient supplement that causes similar changes (transcriptomic and promoting longevity and vitality) as a calorie restriction in mice and C. elegans, respectively, but further studies are required to confirm these effects in humans.
KEYWORDS:
aging; longevity; micronutrient; nutrition; transcriptome

Impact of flaxseed supplementation on plasma lipoprotein(a) concentrations: A systematic review and meta-analysis of randomized controlled trials.
Hadi A, Askarpour M, Ziaei R, Venkatakrishnan K, Ghaedi E, Ghavami A.
Phytother Res. 2020 Feb 19. doi: 10.1002/ptr.6640. [Epub ahead of print] Review.
PMID: 32073724
Abstract
The aim of the study was to investigate the impact of supplementation with flaxseed on plasma lipoprotein(a) [Lp(a)] levels through a systematic review and meta-analysis of eligible randomized placebo-controlled trials. PubMed, Scopus, Cochrane Library, and ISI Web of Science were searched for randomized controlled trials (RCTs) which have been published up to November 2019. RCTs that investigated the effect of flaxseed supplementation on plasma Lp(a) levels in adults were included for final analysis. The random effects model was used for calculating the overall effects. Meta-analysis of 7 selected RCTs with 629 individuals showed significant lowering effect of flaxseed supplementation on Lp(a) (MD -2.06 mg/dl; 95% CI: -3.846, -0.274, p = .024), without considerable heterogeneity between studies (p = .986, I2 = 0%). Subgroup analysis also revealed that longer duration only showed significant lowering effect of flaxseed supplementation on Lp(a). This meta-analysis has shown that flaxseed supplementation might significantly decrease plasma Lp(a) levels. Future well-designed and long-term clinical trials are required to confirm these results.
KEYWORDS:
flaxseed; lipoprotein(a); meta-analysis; systematic review

Dose-Response Relation between Tea Consumption and Risk of Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis of Population-Based Studies.
Chung M, Zhao N, Wang D, Shams-White M, Karlsen M, Cassidy A, Ferruzzi M, Jacques PF, Johnson EJ, Wallace TC.
Adv Nutr. 2020 Feb 19. pii: nmaa010. doi: 10.1093/advances/nmaa010. [Epub ahead of print]
PMID: 32073596
Abstract
Tea flavonoids have been suggested to offer potential benefits to cardiovascular health. This review synthesized the evidence on the relation between tea consumption and risks of cardiovascular disease (CVD) and all-cause mortality among generally healthy adults. PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Food Science and Technology Abstracts, and Ovid CAB Abstract databases were searched to identify English-language publications through 1 November 2019, including randomized trials, prospective cohort studies, and nested case-control (or case-cohort) studies with data on tea consumption and risk of incident cardiovascular events (cardiac or peripheral vascular events), stroke events (including mortality), CVD-specific mortality, or all-cause mortality. Data from 39 prospective cohort publications were synthesized. Linear meta-regression showed that each cup (236.6 mL)  increase in daily tea consumption (estimated 280 mg  and 338 mg  total flavonoids/d for black and green tea, respectively) was associated with an average 4% lower risk of CVD mortality, a 2% lower risk of CVD events, a 4% lower risk of stroke, and a 1.5% lower risk of all-cause mortality. Subgroup meta-analysis results showed that the magnitude of association was larger in elderly individuals for both CVD mortality (n = 4; pooled adjusted RR: 0.89; 95% CI: 0.83, 0.96; P = 0.001), with large heterogeneity (I2 = 72.4%), and all-cause mortality (n = 3; pooled adjusted RR: 0.92; 95% CI: 0.90, 0.94; P < 0.0001; I2 = 0.3%). Generally, studies with higher risk of bias appeared to show larger magnitudes of associations than studies with lower risk of bias. Strength of evidence was rated as low and moderate (depending on study population age group) for CVD-specific mortality outcome and was rated as low for CVD events, stroke, and all-cause mortality outcomes. Daily tea intake as part of a healthy habitual dietary pattern may be associated with lower risks of CVD and all-cause mortality among adults.
KEYWORDS:
Camellia sinensis ; all-cause mortality; cardiovascular disease; systematic review; tea

The Clinical Significance of the Failure to Perceive Vertigo in the Postcaloric Period Despite a Robust Caloric Response.
Piker EG, Jacobson GP, Romero D, Wang Y, Smith K.
Am J Audiol. 2020 Feb 11:1-9. doi: 10.1044/2019_AJA-19-00036. [Epub ahead of print]
PMID: 32073288
Abstract
Purpose The purpose of this project was to explore the association between the perception of motion during caloric testing and two tasks associated with central vestibular processing: postural stability and visuospatial memory. Method This was a prospective study of 25 patients who were found to have nonvestibular etiologies of their symptoms and normal vestibular function test results and who underwent caloric testing with a mean maximum slow phase eye velocity for each irrigation of 15° or greater. Following each caloric irrigation, patients were asked whether they had any sensation of movement. Patients were grouped based on the presence or absence of motion during the caloric exam (motion perception vs. absent perception). Postural stability was assessed using computerized dynamic posturography, and visuospatial memory was assessed using a memory match card game application. Results There were no significant differences between groups on any measures of peripheral vestibular function. However, the Absent Perception Group showed greater postural instability during Condition 5 of posturography and performed significantly worse on a task of visuospatial working memory. Both age and absence of motion perception predicted abnormal performance on measures of postural stability and visuospatial working memory. Conclusions There appears to be clinical implications to a lack of motion perception during the caloric exam in patients with an otherwise normal peripheral vestibular system. Based on the current findings, we are unable to determine whether differences in postural stability and visuospatial memory were due to age or a central vestibular processing deficit.

Waist Circumference and Risk of Liver Cancer: A Systematic Review and Meta-Analysis of over 2 Million Cohort Study Participants.
Rahmani J, Kord Varkaneh H, Kontogiannis V, Ryan PM, Bawadi H, Fatahi S, Zhang Y.
Liver Cancer. 2020 Jan;9(1):6-14. doi: 10.1159/000502478. Epub 2019 Oct 8. Review.
PMID: 32071905
Abstract
PURPOSE:
Liver cancer is the sixth most common type of cancer worldwide, and waist circumference (WC) is associated with its risk beyond body mass index (BMI). This dose-response meta-analysis was performed to investigate the association between WC and the risk of incident liver cancer using prospective cohort studies.
METHODS:
A comprehensive systematic search was conducted in MEDLINE/PubMed, Web of Science databases, Scopus, and Coch-rane from inception to May 2019. Studies with retrospective or prospective cohort design that reported hazard ratio (HR), risk ratio, or odds ratio, and the corresponding 95% confidence intervals (CI) for liver cancer based on WC categories were included in this meta-analysis. Combined HRs with 95% CIs was estimated by DerSimonian and Laird random-effects models.
RESULTS:
Associations between WC and liver cancer were reported in 5 articles with 2,547,188 participants. All studies were published between 2013 and 2019. Pooled results showed a strong significant association with minimum heterogeneity between WC and risk of liver cancer (HR 1.59, 95% CI 1.38-1.83, p_{heterogeneity} = 0.42: I² = 0%). Moreover, a dose-response model indicated a significant positive association between WC and risk of liver cancer (exp(b) = 1.018, p < 0.001).
CONCLUSIONS:
This systematic review and dose-response meta-analysis highlights WC as a significant risk factor related to the incidence of liver cancer.
KEYWORDS:
Central obesity; Liver cancer; Waist circumference

[AlPater]

Association between employment status and risk of all-cause and cause-specific mortality: a population-based prospective cohort study.
Nie J, Wang J, Aune D, Huang W, Xiao D, Wang Y, Chen X.
J Epidemiol Community Health. 2020 Feb 21. pii: jech-2019-213179. doi: 10.1136/jech-2019-213179. [Epub ahead of print]
PMID: 32086372
Abstract
BACKGROUND:
Unemployment has been reported to be associated with an increased risk of mortality. While most available studies focused on the effects of temporary unemployment on mortality, it remains unclear whether similar trends can be found in subjects who were never employed or are retirement. Therefore, this study examined the associations between temporary unemployment, never employed and retirement, integrating the risk of all-cause and cause-specific mortality in US adults.
METHODS:
Data from the National Health Interview Survey from 2001 to 2013 Linked Mortality files through 31 December 2015 were used. A total of 282 364 participants aged 18 to 65 years were included. Their employment status was categorised into four groups: employed, never employed, temporary unemployed and retired.
RESULTS:
During the mean follow-up time of 8.2 years, 12 645 subjects died from a variety of causes. Compared with employed participants, temporary unemployed, never employed or retired participants faced an increased risk of mortality for all-cause (temporary unemployed HR 1.76, 95% CI 1.67 to 1.86; never employed HR 1.63, 95% CI 1.47 to 1.81; retired HR 1.27, 95% CI 1.17 to 1.37). Cause-specific mortality analysis showed that compared with employed participants, temporary unemployed or never employed participants faced a significantly increased risk of mortality from cancer, cardiovascular disease, chronic lower respiratory disease, diabetes and kidney disease.
CONCLUSION:
This study showed that retired, temporary unemployed and never employed participants aged 18 to 65 years were strongly associated with higher mortality, indicating that both temporary and long-term unemployment are associated with a higher risk of mortality and adversely affect longevity.
KEYWORDS:
cohort studies; mortality; unemployment

Dairy and related nutrient intake and risk of uterine leiomyoma: a prospective cohort study.
Orta OR, Terry KL, Missmer SA, Harris HR.
Hum Reprod. 2020 Feb 22. pii: dez278. doi: 10.1093/humrep/dez278. [Epub ahead of print]
PMID: 32086510
Abstract
STUDY QUESTION:
Is there an association between consumption of dairy foods and related nutrients and risk of uterine leiomyoma?
SUMMARY ANSWER:
While dairy consumption was not consistently associated with uterine leiomyoma risk, intake of yogurt and calcium from foods may reduce risk of uterine leiomyoma.
WHAT IS KNOWN ALREADY:
Two studies have examined the association between dairy intake and uterine leiomyoma risk with inconsistent results. Dairy foods have been inversely associated with inflammation and tumorigenesis, suggesting that vitamins and minerals concentrated in these dietary sources may influence uterine leiomyoma risk.
STUDY DESIGN, SIZE, DURATION:
A prospective cohort study was carried out using data collected from 81 590 premenopausal women from 1991 to 2009 as part of the Nurses' Health Study II cohort.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
Diet was assessed with a validated food frequency questionnaire every 4 years. Cases were restricted to self-reported ultrasound or hysterectomy-confirmation uterine leiomyoma. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CI.
MAIN RESULTS AND THE ROLE OF CHANCE:
Eight thousand one hundred and forty-two cases of ultrasound or hysterectomy-confirmed uterine leiomyoma were diagnosed over an 18-year period. When compared to participants who consumed two servings a week of total dairy foods, participants who consumed four or more servings had a borderline significant 8% reduced risk of uterine leiomyoma (HR = 0.92, 95% CI = 0.85, 1.00; ptrend = 0.19). When the association between specific dairy foods and uterine leiomyoma was examined, the relation between dairy-food intake and uterine leiomyoma appeared to be driven primarily by yogurt consumption (HR for 2+ servings/day = 0.76; 95% CI = 0.55, 1.04 compared to <=4 servings/week; ptrend = 0.03); however, there was a small number of cases in the 2+ servings/day group (n = 39). Of the nutrients examined, the association was strongest for calcium from foods (HR fifth quintile = 0.92, 95% CI = 0.86, 0.99; ptrend = 0.04).
LIMITATIONS, REASONS FOR CAUTION:
Some cases of uterine leiomyoma were likely misclassified, particularly those that were asymptomatic. It is possible that dairy product constituents reduce uterine leiomyoma symptomology rather than development, giving the appearance of a protective effect on leiomyoma development: no data on uterine leiomyoma symptomology were available. We did not have vitamin and mineral concentrations from actual blood levels. Similarly, there is the potential for misclassification of participants based on predicted 25(OH)D, and changes in vitamin D supplementation over time may have impacted prediction models for 25(OH)D. Further, some error in the self-reporting of dietary intake is expected. Given our prospective design, it is likely that these misclassifications were non-differential with respect to the outcome, likely biasing estimates toward the null.
WIDER IMPLICATIONS OF THE FINDINGS:
While no clear association between overall dairy consumption and uterine leiomyoma risk was observed, our findings suggest that intake of yogurt and calcium from foods may reduce risk of uterine leiomyoma.
STUDY FUNDING/COMPETING INTEREST(S):
This work was supported by research grant HD081064 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The Nurses' Health Study II is supported by the Public Health Service grant UM1 CA176726 from the National Cancer Institute, NIH, U.S. Department of Health and Human Services. H.R.H. is supported by the National Cancer Institute, National Institutes of Health (K22 CA193860). There are no conflicts of interest to declare.
KEYWORDS:
calcium; dairy foods; diet; fibroids; uterine leiomyoma; vitamin D; yogurt

Is Our Diet Turning Our Gut Microbiome Against Us?
Heidenreich PA, Mamic P.
J Am Coll Cardiol. 2020 Feb 25;75(7):773-775. doi: 10.1016/j.jacc.2019.12.023. No abstract available.
PMID: 32081287
https://sci-hub.tw/10.1016/j.jacc.2019.12.023
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Long-Term Changes in Gut Microbial Metabolite Trimethylamine N-Oxide and Coronary Heart Disease Risk.
Heianza Y, Ma W, DiDonato JA, Sun Q, Rimm EB, Hu FB, Rexrode KM, Manson JE, Qi L.
J Am Coll Cardiol. 2020 Feb 25;75(7):763-772. doi: 10.1016/j.jacc.2019.11.060.
PMID: 32081286
Abstract
BACKGROUND:
A gut-microbial metabolite, trimethylamine N-oxide (TMAO), has been associated with coronary atherosclerotic burden. No previous prospective study has addressed associations of long-term changes in TMAO with coronary heart disease (CHD) incidence.
OBJECTIVES:
The purpose of this study was to investigate whether 10-year changes in plasma TMAO levels were significantly associated with CHD incidence.
METHODS:
This prospective nested case-control study included 760 healthy women at baseline. Plasma TMAO levels were measured both at the first (1989 to 1990) and the second (2000 to 2002) blood collections; 10-year changes (Δ) in TMAO were calculated. Incident cases of CHD (n = 380) were identified after the second blood collection through 2016 and were matched to controls (n = 380).
RESULTS:
Regardless of the initial TMAO levels, 10-year increases in TMAO from the first to second blood collection were significantly associated with an increased risk of CHD (relative risk [RR] in the top tertile: 1.58 [95% confidence interval (CI): 1.05 to 2.38]; RR per 1-SD increment: 1.33 [95% CI: 1.06 to 1.67]). Participants with elevated TMAO levels (the top tertile) at both time points showed the highest RR of 1.79 (95% CI: 1.08 to 2.96) for CHD as compared with those with consistently low TMAO levels. Further, we found that the ΔTMAO-CHD relationship was strengthened by unhealthy dietary patterns (assessed by the Alternate Healthy Eating Index) and was attenuated by healthy dietary patterns (p interaction = 0.008).
CONCLUSIONS:
Long-term increases in TMAO were associated with higher CHD risk, and repeated assessment of TMAO over 10 years improved the identification of people with a higher risk of CHD. Diet may modify the associations of ΔTMAO with CHD risk.
KEYWORDS:
coronary heart disease; diet; gut-microbial metabolites; prospective cohort study; risk factors

Atrial fibrillation in the elderly general population: a 30-year follow-up from 70 to 100 years of age.
Lernfelt G, Mandalenakis Z, Hornestam B, Lernfelt B, Rosengren A, Sundh V, Hansson PO.
Scand Cardiovasc J. 2020 Feb 21:1-7. doi: 10.1080/14017431.2020.1729399. [Epub ahead of print]
PMID: 32079431
Abstract
Objectives. There is limited knowledge of atrial fibrillation (AF) incidence among the very old. Data from longitudinal cohort studies may give us a better insight. The aim of the study was to investigate the incidence rate and prevalence of AF, as well as the impact of AF on mortality, in the general population, from 70 to 100 years of age. Design. This was a population-based prospective cohort study where three representative samples of 70-year-old men and women (n = 2,629) from the Gerontological and Geriatric Populations Studies in Gothenburg (H-70) were included between 1971 and 1982. The participants were examined at age 70 years and were re-examined repeatedly until 100 years of age. AF was diagnosed according to a 12-lead electrocardiogram (ECG) recording at baseline and follow-up examinations, from the Swedish National Patient Register (NPR), or from the Cause of Death Register. Results. The cumulative incidence of AF from 70 to 100 years of age was 65.6% for men and 52.8% for women. Mortality was significantly higher in participants with AF compared with those without, rate ratio (RR) 1.92 (95% CI 1.73-2.14). In a subgroup analysis comprising only participants with AF diagnosed by ECG at screening, the RR for death was 1.29 (95% C.I: 1.03-1.63). Conclusions. Among persons surviving to age 70, the cumulative incidence of AF was over 50% during follow-up. Mortality rate was twice as high in participants with AF compared to participants without AF. Among participants with AF first recorded at a screening examination, the increased risk was only 29%.
KEYWORDS:
Atrial fibrillation; incidence; mortality; prevalence

Association of the Intensive Lifestyle Intervention With Total Knee Replacement in the Look AHEAD (Action for Health in Diabetes) Clinical Trial.
Richey PA, Johnson KC, Neiberg RH, Bahnson JL, Singhal K, Coday M, Thomas F, Lewis CE, Mihalko WM; Look AHEAD Research Group.
J Arthroplasty. 2020 Feb 18. pii: S0883-5403(20)30094-2. doi: 10.1016/j.arth.2020.01.057. [Epub ahead of print]
PMID: 32085906
Abstract
BACKGROUND:
Evidence has established obesity as a risk factor for total knee replacement (TKR) due to osteoarthritis. Obesity is a risk factor for TKR. Randomized trials such as Look AHEAD (Action for Health in Diabetes) have shown long-term successful weight loss with an intensive lifestyle intervention (ILI). It is unknown, however, if intentional weight loss can reduce the risk of TKR.
METHODS:
Look AHEAD randomized persons aged 45-76 with type 2 diabetes who had overweight or obesity to either an ILI to achieve/maintain 7% weight loss or to standard diabetes support and education (DSE). Reported knee pain was assessed using the Visual Analog Scale and Western Ontario McMaster University Osteoarthritis Index questionnaire in 5125 participants without previous TKR. Cox proportional hazard regression was used to model differences in risk of TKR in relation to randomization group assignment (ILI vs DSE) along with baseline body mass index category and baseline knee pain as potential confounders from baseline through Look AHEAD-Extension.
RESULTS:
Baseline mean ± SD Western Ontario McMaster University Osteoarthritis Index knee pain scores did not differ by treatment assignment (ILI: 3.6 ± 2.9, DSE: 3.9 ± 3.0, P = .08); as expected due to randomization. During follow up, the 631 (12%) participants who reported having a TKR were more likely to have been heavier (P < .001) and older (P < .001) at enrollment, but risk of TKR did not differ by treatment group assignment (hazard ratio {HR} 1.07, 95% confidence interval [CI] 0.91-1.25, P = .43). Heterogeneity of treatment effect was observed according to baseline knee pain (interaction P = .02). In persons without knee pain at baseline, there was a 29% reduced risk of TKR in ILI compared to DSE (HR 0.71, 95% CI 0.52-0.96). However, in persons with knee pain at baseline, there was no statistically significant association of treatment assignment with respect to subsequent TKR incidence (HR 1.11, 95% CI 0.92-1.33).

CONCLUSION:
Findings suggest that intensive lifestyle change including physical activity, dietary restriction and behavioral changes to achieve weight loss for prevention of TKR may be most effective in preventing TKR prior to the development of knee pain.
KEYWORDS:
arthroplasty; knee; obesity; osteoarthritis; physical activity; weight loss

Edited February 23, 2020 by AlPater

[AlPater]

Associations of C-reactive protein and fibrinogen with mortality from all-causes, cardiovascular disease and cancer among U.S. adults.
Liu J, Zhang Y, Lavie CJ, Tabung FK, Xu J, Hu Q, He L, Zhang Y.
Prev Med. 2020 Feb 22:106044. doi: 10.1016/j.ypmed.2020.106044. [Epub ahead of print]
PMID: 32097752
Abstract
C-reactive protein (CRP) and fibrinogen are associated with an increased risk of death with suggested differences by gender, diet quality and race/ethnicity. However, the current evidence is limited. We used data including 8646 men and 9880 women from the National Health and Nutrition Examination Survey (NHANES) Linked Morality cohort (1999-2011) to investigate the associations of CRP and fibrinogen with mortality overall and by gender, race/ethnicity and diet quality. Cox-proportional hazard model was used to quantify the associations. With a median follow-up of 6 years, a strong dose-response relationship was observed between CRP levels and mortality risk in men after multivariable adjustment. For subjects who survived the first two years, the adjusted hazard ratios (HRs) for total mortality across quartiles (from lower to higher) of CRP were 1.97 (95% CI: 0.62-6.33), 1.89 (0.59, 6.06) and 6.34 (2.28-17.7) (P for trend <0.001). For cardiovascular disease (CVD) mortality, its association with CRP varied by diet quality. For cancer mortality, its association differed by history of cancer, and positive associations were observed only among subjects with history of cancer. In contrast, no such association of CRP with mortality was found in women. For fibrinogen, we observed its positive association with total mortality and the HRs across quartiles of fibrinogen (from lower to higher) were 1.21 (0.88, 1.67), 1.49 (1.22, 1.82) and 1.99 (1.56, 2.55). The association with CVD mortality differed by diet quality whereas no association was found with cancer mortality. Our findings suggest that higher levels of CRP and fibrinogen were associated with lower survival from total and CVD; the associations of CRP with mortality were more pronounced in men than women. Diet quality is an effect modifier for the association of CRP and fibrinogen with CVD mortality.
KEYWORDS:
C-reactive protein; Cancer; Cardiovascular disease; Diet quality; Fibrinogen; Mortality

Dairy, soy, and risk of breast cancer: those confounded milks.
Fraser GE, Jaceldo-Siegl K, Orlich M, Mashchak A, Sirirat R, Knutsen S.
Int J Epidemiol. 2020 Feb 25. pii: dyaa007. doi: 10.1093/ije/dyaa007. [Epub ahead of print]
PMID: 32095830
Abstract
BACKGROUND:
Associations between soy, dairy intakes and breast cancer risk are inconsistent. No studies exist with large numbers of dairy consumers and soy consumers to assess mutual confounding.
METHODS:
The study cohort contains 52 795 North American women, initially free of cancer, followed for 7.9 years (29.7% were Black). Dietary intakes were estimated from food frequency questionnaires and, for 1011 calibration study subjects, from six structured 24-h dietary recalls. Incident invasive breast cancers were detected mainly by matching with cancer registries. Analyses used multivariable proportional hazards regression.
RESULTS:
The participants (mean age of 57.1 years) experienced 1057 new breast cancer cases during follow-up. No clear associations were found between soy products and breast cancer, independently of dairy. However, higher intakes of dairy calories and dairy milk were associated with hazard ratios (HRs) of 1.22 [95% confidence interval (CI): 1.05-1.40] and 1.50 (95% CI 1.22-1.84), respectively, comparing 90th to 10th percentiles of intakes. Full fat and reduced fat milks produced similar results. No important associations were noted with cheese and yogurt. Substituting median intakes of dairy milk users by those of soy milk consumers was associated with HR of 0.68 (95% CI: 0.55-0.85). Similar-sized associations were found among pre- and post-menopausal cases, with CIs also excluding the null in estrogen receptor (ER+, ER-), and progesterone receptor (PR+) cancers. Less biased calibrated measurement-error adjusted regressions demonstrated yet stronger, but less precise, HRs and CIs that still excluded the null.
CONCLUSIONS:
Higher intakes of dairy milk were associated with greater risk of breast cancer, when adjusted for soy intake. Current guidelines for dairy milk consumption could be viewed with some caution.
KEYWORDS:
Soy isoflavones; Western population; breast cancer; meat analogues; soy intake; soy milk; tofu

High Consumption of Soft Drinks Is Associated with an Increased Risk of Fracture: A 7-Year Follow-Up Study.
Chen L, Liu R, Zhao Y, Shi Z.
Nutrients. 2020 Feb 19;12(2). pii: E530. doi: 10.3390/nu12020530.
PMID: 32092922
Abstract
(1) Background: Fracture causes a substantial burden to society globally. Some studies have found that soft drinks consumption was associated with the risk of fractures. We aimed to assess the association in the Chinese population; (2) Methods: Data from 17,383 adults aged 20 to 75 years old attending the China Health and Nutrition Survey (CHNS) between 2004 and 2011 were analyzed. Soft drinks consumption and fracture occurrence were self-reported. The cross-sectional and longitudinal associations between soft drink and fracture was assessed using multivariable mixed-effect logistic regression and Cox regression; (3) Results: After adjusting for sociodemographic and lifestyle factors and dietary patterns, compared with those who did not consume soft drinks, participants with daily consumption of soft drinks had an odds ratio (95%CI) of 2.72 (95%CI: 1.45-5.09) for fracture. During a mean 5-year follow-up, there were 569 incident fracture cases. Compared with non-consumers, those with daily soft drinks consumption had a hazard ratio (95%CI) of 4.69 (95%CI: 2.80-7.88) for incident fracture; (4) Conclusions: Soft drinks consumption is directly associated with the risk of fracture. Reducing soft drinks consumption should be considered as an important strategy for individual and population levels to maintain bone health.
KEYWORDS:
China Health and Nutrition Survey; epidemiology; fracture; longitudinal study; soft drinks

The effect of zinc supplementation on blood pressure: a systematic review and dose-response meta-analysis of randomized-controlled trials.
Mousavi SM, Mofrad MD, do Nascimentoe IJB, Milajerdi A, Mokhtari T, Esmaillzadeh A.
Eur J Nutr. 2020 Feb 24. doi: 10.1007/s00394-020-02204-5. [Epub ahead of print] Review.
PMID: 32090294
Abstract
PURPOSE:
Despite previous investigations on the effects of zinc supplementation on blood pressure, inconsistent findings are available in this regard. Therefore, we conducted a systematic review and meta-analysis of randomized clinical trials on the effects of zinc supplementation on blood pressure (BP) in adults.
METHODS:
Relevant studies published up to September 2019 were searched through PubMed/Medline, Scopus, ISI Web of Science, and Google Scholar using suitable keywords. All randomized clinical trials (RCTs) that examined the effect of oral zinc supplementation on systolic blood pressure (SBP) or diastolic blood pressure (DBP) in adults were included.
RESULTS:
Overall, nine trials were included in our study. Zinc supplementation significantly reduced SBP compared to the control [weighted mean differences (WMD) - 1.49 mmHg; 95% CI - 2.85 to - 0.13; P = 0.03]. However, zinc supplementation had no significant effects on DBP (WMD - 0.88 mmHg; 95% CI - 2.04 to 0.29; P = 0.14). Nonlinear analysis failed to indicate a significant influence of supplementation dosage or duration on both SBP and DBP. Sensitivity analysis showed that no individual study had a significant impact on our final results. In addition, we found no evidence for the presence of small-study effects among studies for both SBP and DBP.
CONCLUSION:
We found a significant reduction in SBP following zinc supplementation. However, zinc supplementation had no significant effect on DBP. In addition, no nonlinear association was found between supplementation dosage and duration with changes in both SBP and DBP. Further RCTs using different dosages of zinc in various durations are required to confirm our conclusion.
KEYWORDS:
Blood pressure; Diastolic blood pressure; Meta-analysis; Systolic blood pressure; Zinc

The associations of major foods and fibre with risks of ischaemic and haemorrhagic stroke: a prospective study of 418 329 participants in the EPIC cohort across nine European countries.
Tong TYN, Appleby PN, Key TJ, Dahm CC, Overvad K, Olsen A, Tjønneland A, Katzke V, Kühn T, Boeing H, Karakatsani A, Peppa E, Trichopoulou A, Weiderpass E, Masala G, Grioni S, Panico S, Tumino R, Boer JMA, Verschuren WMM, Quirós JR, Agudo A, Rodríguez-Barranco M, Imaz L, Chirlaque MD, Moreno-Iribas C, Engström G, Sonestedt E, Lind M, Otten J, Khaw KT, Aune D, Riboli E, Wareham NJ, Imamura F, Forouhi NG, di Angelantonio E, Wood AM, Butterworth AS, Perez-Cornago A.
Eur Heart J. 2020 Feb 24. pii: ehaa007. doi: 10.1093/eurheartj/ehaa007. [Epub ahead of print]
PMID: 32090257
Abstract
AIM:
To investigate the associations between major foods and dietary fibre with subtypes of stroke in a large prospective cohort.
METHODS AND RESULTS:
We analysed data on 418 329 men and women from nine European countries, with an average of 12.7 years of follow-up. Diet was assessed using validated country-specific questionnaires which asked about habitual intake over the past year, calibrated using 24-h recalls. Multivariable-adjusted Cox regressions were used to estimate hazard ratios (HRs) for ischaemic and haemorrhagic stroke associated with consumption of red and processed meat, poultry, fish, dairy foods, eggs, cereals, fruit and vegetables, legumes, nuts and seeds, and dietary fibre. For ischaemic stroke (4281 cases), lower risks were observed with higher consumption of fruit and vegetables combined (HR; 95% CI per 200 g/day higher intake, 0.87; 0.82-0.93, P-trend < 0.001), dietary fibre (per 10 g/day, 0.77; 0.69-0.86, P-trend < 0.001), milk (per 200 g/day, 0.95; 0.91-0.99, P-trend = 0.02), yogurt (per 100 g/day, 0.91; 0.85-0.97, P-trend = 0.004), and cheese (per 30 g/day, 0.88; 0.81-0.97, P-trend = 0.008), while higher risk was observed with higher red meat consumption which attenuated when adjusted for the other statistically significant foods (per 50 g/day, 1.07; 0.96-1.20, P-trend = 0.20). For haemorrhagic stroke (1430 cases), higher risk was associated with higher egg consumption (per 20 g/day, 1.25; 1.09-1.43, P-trend = 0.002).
CONCLUSION:
Risk of ischaemic stroke was inversely associated with consumption of fruit and vegetables, dietary fibre, and dairy foods, while risk of haemorrhagic stroke was positively associated with egg consumption. The apparent differences in the associations highlight the importance of examining ischaemic and haemorrhagic stroke subtypes separately.
KEYWORDS:
Diet; Fibre; Fruit; Haemorrhagic stroke; Ischaemic stroke; Vegetables

[AlPater]

Vegetarian diet and incidence of total, ischemic, and hemorrhagic stroke in 2 cohorts in Taiwan.
Chiu THT, Chang HR, Wang LY, Chang CC, Lin MN, Lin CL.
Neurology. 2020 Feb 26. pii: 10.1212/WNL.0000000000009093. doi: 10.1212/WNL.0000000000009093. [Epub ahead of print]
PMID: 32102976
Abstract
OBJECTIVE:
To determine how a vegetarian diet affects stroke incidence in 2 prospective cohorts and to explore whether the association is modified by dietary vitamin B12 intake.
METHODS:
Participants without stroke in the Tzu Chi Health Study (cohort 1, n = 5,050, recruited in 2007-2009) and the Tzu Chi Vegetarian Study (cohort 2, n = 8,302, recruited in 2005) were followed until the end of 2014. Diet was assessed through food frequency questionnaires in both cohorts at baseline. Stroke events and baseline comorbidities were identified through the National Health Insurance Research Database. A subgroup of 1,528 participants in cohort 1 were assessed for serum homocysteine, vitamin B12, and folate. Associations between vegetarian diet and stroke incidences were estimated by Cox regression with age as time scale, adjusted for sex, education, smoking, alcohol, physical activities, body mass index (only in cohort 1), hypertension, diabetes, dyslipidemia, and ischemic heart diseases.
RESULTS:
Vegetarians had lower serum vitamin B12 and higher folate and homocysteine than nonvegetarians. In cohort 1, 54 events occurred in 30,797 person-years follow-up. Vegetarians (vs nonvegetarians) experienced lower risk of ischemic stroke (hazard ratio {HR}, 0.26; 95% confidence interval [CI], 0.08-0.88). In cohort 2, 121 events occurred in 76,797 person-years follow-up. Vegetarians (vs nonvegetarians) experienced lower risk of overall stroke (HR, 0.52; 95% CI, 0.33-0.82), ischemic stroke (HR, 0.41; 95% CI, 0.19-0.88), and hemorrhagic stroke (HR, 034; 95% CI, 0.12-1.00). Our explorative analysis showed that vitamin B12 intake may modify the association between vegetarian diet and overall stroke (p interaction = 0.046).
CONCLUSION:
Taiwanese vegetarian diet is associated with a lower risk of ischemic and hemorrhagic strokes.

A high consumption of tomato and lycopene is associated with a lower risk of cancer mortality: results from a multi-ethnic cohort.
Mazidi M, Ferns GA, Banach M.
Public Health Nutr. 2020 Feb 27:1-7. doi: 10.1017/S1368980019003227. [Epub ahead of print]
PMID: 32102720
https://sci-hub.tw/10.1017/S1368980019003227
Abstract
OBJECTIVE:
We investigated the association between the consumption of tomato and lycopene and cancer mortality among US adults.
DESIGN:
Prospective.
SETTING:
The National Health and Nutrition Examination Survey (1999-2010).
PARTICIPANTS:
Participants with estimated dietary data on tomato and lycopene consumption were included. Outcome data up until 31 December 2011 were also ascertained. Cox proportional hazard regression models were used to relate baseline tomato and lycopene consumption with cancer mortality. We conducted a competing-risk survival analysis to account for deaths from other causes.
RESULTS:
Adjusted Cox models showed that tomato and lycopene intake were inversely related (hazard ratio (95 % CI)) to cancer mortality: 0·86 (0·81, 0·92) and 0·79 (0·74, 0·82), respectively. In the adjusted competing-risk models, the sub-hazard ratios (95 % CI) were 0·89 (0·83, 0·94) and 0·82 (0·78, 0·86) for cancer mortality for tomato and lycopene intake, respectively. No significant interaction was found for the association between tomato and lycopene consumption and cancer mortality while comparing older (aged >50 years) v. younger adults (Pinteraction > 0·173 for all) and obese v. non-obese (Pinteraction > 0·352 for all).
CONCLUSIONS:
Our results demonstrate the potential beneficial effects of a high dietary intake of tomato and lycopene on cancer death. Further prospective studies are needed to explore the association.
KEYWORDS:
Cancer; Lycopene; Mortality; Tomato

A high consumption of tomato and lycopene is associated with a lower risk of cancer mortality: results from a multi-ethnic cohort.
Mazidi M, Ferns GA, Banach M.
Public Health Nutr. 2020 Feb 27:1-7. doi: 10.1017/S1368980019003227. [Epub ahead of print]
PMID: 32102720
Abstract
OBJECTIVE:
We investigated the association between the consumption of tomato and lycopene and cancer mortality among US adults.
DESIGN:
Prospective.
SETTING:
The National Health and Nutrition Examination Survey (1999-2010).
PARTICIPANTS:
Participants with estimated dietary data on tomato and lycopene consumption were included. Outcome data up until 31 December 2011 were also ascertained. Cox proportional hazard regression models were used to relate baseline tomato and lycopene consumption with cancer mortality. We conducted a competing-risk survival analysis to account for deaths from other causes.
RESULTS:
Adjusted Cox models showed that tomato and lycopene intake were inversely related (hazard ratio (95 % CI)) to cancer mortality: 0·86 (0·81, 0·92) and 0·79 (0·74, 0·82), respectively. In the adjusted competing-risk models, the sub-hazard ratios (95 % CI) were 0·89 (0·83, 0·94) and 0·82 (0·78, 0·86) for cancer mortality for tomato and lycopene intake, respectively. No significant interaction was found for the association between tomato and lycopene consumption and cancer mortality while comparing older (aged >50 years) v. younger adults (Pinteraction > 0·173 for all) and obese v. non-obese (Pinteraction > 0·352 for all).
CONCLUSIONS:
Our results demonstrate the potential beneficial effects of a high dietary intake of tomato and lycopene on cancer death. Further prospective studies are needed to explore the association.
KEYWORDS:
Cancer; Lycopene; Mortality; Tomato

Habitual Fish Consumption, n-3 Fatty Acids, and Nuclear Magnetic Resonance Lipoprotein Subfractions in Women.
Amigó N, Akinkuolie AO, Chiuve SE, Correig X, Cook NR, Mora S.
J Am Heart Assoc. 2020 Mar 3;9(5):e014963. doi: 10.1161/JAHA.119.014963. Epub 2020 Feb 27.
PMID: 32102617
Abstract
Background Supplementation with omega-3 (n-3) fatty acid or dietary fish may protect against atherosclerosis, but the potential mechanisms are unclear. Prior studies found modest triglyceride-lowering effects and slight increases in LDL (low-density lipoprotein) cholesterol. Limited evidence has examined n-3 effects on more detailed lipoprotein biomarkers. Methods and Results We conducted a study of 26 034 healthy women who reported information on fish and n-3 intake from a 131-item food-frequency questionnaire. We measured plasma lipids, apolipoproteins, and nuclear magnetic resonance spectroscopy lipoproteins and examined their associations with dietary intake of fish, total n-3, and the n-3 subtypes (eicosapentaenoic, docosahexaenoic, and α-linolenic acids). Top- versus bottom-quintile intake of fish and n-3 were significantly associated with lower triglyceride and large VLDL (very-low-density lipoprotein) particles. Fish intake, but not total n-3, was positively associated with total cholesterol, LDL cholesterol, apolipoprotein B, and larger LDL size, but only α-linolenic acid was associated with lower LDL cholesterol. Total n-3, docosahexaenoic acid, and α-linolenic acid intake were also positively associated with larger HDL (high-density lipoprotein) size and large HDL particles. High eicosapentaenoic acid intake was significantly associated with only a decreased level of VLDL particle concentration and VLDL triglyceride content. The n-3 fatty acids had some similarities but also differed in their associations with prospective cardiovascular disease risk patterns. Conclusions Higher consumption of fish and n-3 fatty acids were associated with multiple measures of lipoproteins that were mostly consistent with cardiovascular prevention, with differences noted for high intake of eicosapentaenoic acid versus docosahexaenoic acid and α-linolenic acid that were apparent with more detailed lipoprotein phenotyping. These hypothesis-generating findings warrant further study in clinical trials.
KEYWORDS:
fish; nuclear magnetic resonance lipoprotein subfractions; n‐3

Association between C reactive protein and all-cause mortality in the ELSA-Brasil cohort.
Maluf CB, Barreto SM, Giatti L, Ribeiro AL, Vidigal PG, Azevedo DRM, Griep RH, Matos SMA, Ji C, Cappuccio FP, Miller MA.
J Epidemiol Community Health. 2020 Feb 26. pii: jech-2019-213289. doi: 10.1136/jech-2019-213289. [Epub ahead of print]
PMID: 32102838
Abstract
BACKGROUND:
High-sensitivity C reactive protein (hsCRP) has been proposed as a marker of incident cardiovascular disease and vascular mortality, and may also be a marker of non-vascular mortality. However, most evidence comes from either North American or European cohorts. The present proposal aims to investigate the association of hsCRP with the risk of all-cause mortality in a multiethnic Brazilian population.
METHODS:
Baseline data (2008-2010) of a cohort of 14 238 subjects participating in the Brazilian Longitudinal Study of Adult Health were used. hsCRP was assayed with immunochemistry. The association of baseline covariates with all-cause mortality was calculated by Cox regression for univariate model and adjusted for different confounders after a mean follow-up of 8.0±1.1 years. The final model was adjusted for age, sex, self-rated race/ethnicity, schooling, health behaviours and prevalent chronic disease.
RESULTS:
The risk of death increased steadily by quartiles of hsCRP, from 1.45 (95% CI 1.05 to 2.01) in quartile 2 to 1.95 (95% CI 1.42 to 2.69) in quartile 4, compared with quartile 1. Furthermore, the persistence of a significant graded association after the exclusion of deaths in the first year of follow-up suggests that these results are unlikely to be due to reverse causality. Finally, the HR was unaffected by the exclusion of participants who had self-reported medical history of diabetes, cancer and chronic obstructive pulmonary disease.
CONCLUSIONS:
Our study shows that hsCRP level is associated with mortality in a highly admixed population, independent of a large set of lifestyle and clinical variables.
KEYWORDS:
cohort studies; epidemiology; mortality

The Impact of Health Promotion Interventions on Telomere Length: A Systematic Review.
Qiao S, Jiang Y, Li X.
Am J Health Promot. 2020 Feb 27:890117120906958. doi: 10.1177/0890117120906958. [Epub ahead of print]
PMID: 32103672
Abstract
OBJECTIVES:
The aim of this study was to evaluate the effectiveness of health promotion interventions in delaying telomere shortening (a biomarker for aging).
DATA SOURCE:
PubMed, PsychINFO, EMBASE, CINAHL, and Cochrane Library databases.
STUDY INCLUSION AND EXCLUSION CRITERIA:
Inclusion criteria: (1) empirical studies involving human subjects; (2) health promotion intervention studies including both randomized control trials (RCTs) and non-RCTs.; (3) measured telomere length as an intervention outcome; and (4) were written in English. Exclusion criteria: (1) observational studies without any health promotion intervention practices and (2) did not report intervention effects.
DATA EXTRACTION:
Data extraction was performed by two reviewers following the preferred reporting items for systematic reviews and meta-analysis guidelines.
DATA SYNTHESIS:
Substantial heterogeneity in intervention type and study design in the included studies precluded a meta-analysis. We conducted a narrative synthesis instead.
RESULTS:
Thirty studies were included in the review, of which 16 were RCTs. One-third of the included studies reported significant intervention impacts in delaying telomere shortening, with relatively consistent significant results emerged from weight-loss interventions and interventions involving multiple lifestyle modification components (eg, diet and exercise). Most of supplement intervention studies observed null effects in telomere length.
CONCLUSIONS:
Weight-loss and comprehensive lifestyle intervention strategies show encouraging impacts in delaying telomere shortening. More rigorous studies targeting populations at different age stages through life span are needed.
KEYWORDS:
health promotion intervention; systematic review; telomere length

Magnesium intake and primary liver cancer incidence and mortality in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.
Zhong GC, Peng Y, Wang K, Wan L, Wu YQ, Hao FB, Hu JJ, Gu HT.
Int J Cancer. 2020 Feb 27. doi: 10.1002/ijc.32939. [Epub ahead of print]
PMID: 32105342
Abstract
Epidemiological studies on magnesium intake and primary liver cancer (PLC) are scarce, and no prospective studies have examined the associations of magnesium intake with PLC incidence and mortality. We sought to clarify whether higher magnesium intake from diet and supplements was associated with lower risks of PLC incidence and mortality in the US population. Magnesium intake from diet and supplements was evaluated through a food frequency questionnaire in a cohort of 104,025 participants. Cox regression was employed to calculate hazard ratios for PLC incidence and competing risk regression was employed to calculate sub-distribution hazard ratios for PLC mortality. Restricted cubic spline regression was employed to test nonlinearity. We documented 116 PLC cases during 1,193,513.5 person-years of follow-up and 100 PLC deaths during 1,198,021.3 person-years of follow-up. Total (diet + supplements) magnesium intake was found to be inversely associated with risks of PLC incidence (hazard ratiotertile 3 vs 1 : 0.44; 95% confidence interval: 0.24, 0.80; Ptrend  = 0.0065) and mortality (sub-distribution hazard ratiotertile 3 vs 1 : 0.37; 95% confidence interval: 0.19, 0.71; Ptrend  = 0.0008). Similar results were obtained for dietary magnesium intake. Non-linear inverse dose-response associations with PLC incidence and mortality were observed for both total and dietary magnesium intakes (all Pnon-linearity  < 0.05). In summary, in the US population, a high magnesium intake is associated with decreased risks of PLC incidence and mortality in a non-linear dose-response manner. These findings support that increasing the consumption of foods rich in magnesium may be beneficial in reducing PLC incidence and mortality.
KEYWORDS:
incidence; magnesium; mortality; primary liver cancer

Tomato consumption and intake of lycopene as predictors of the incidence of prostate cancer: the Adventist Health Study-2.
Fraser GE, Jacobsen BK, Knutsen SF, Mashchak A, Lloren JI.
Cancer Causes Control. 2020 Feb 25. doi: 10.1007/s10552-020-01279-z. [Epub ahead of print]
PMID: 32100191
Abstract
PURPOSE:
Studies have controversially suggested that prostate cancer, the most common cancer among Western men, is less common among those with a high intake of tomato products and lycopene. We examine multivariable associations between the intake of tomatoes and lycopene, and risk of prostate cancer.
METHODS:
In a prospective study of 27,934 Adventist men without prevalent cancer, Cox proportional hazard regression analyses were used to address the objectives. Dietary measurement error was partially corrected with regression calibration.
RESULTS:
1226 incident cases of prostate cancer, 355 of them aggressive, were identified during 7.9 years of follow-up. Consumption of canned and cooked tomatoes more than four times a week was associated with a HR = 0.72 (95% CI 0.55, 0.94, P = 0.02) comparing to risk in those never consuming this food. Treating this as a continuous variable, adjusting for confounders, produces a similar result, HR = 0.86 (95% CI 0.75, 0.99), comparing 64 g/day with zero intakes (questionnaire data). Regression calibration, although less precise, suggests a yet stronger and statistically significant inverse relationship, comparing a 24-h dietary recall intake of 71 g/day canned and cooked tomato product, with zero intake. Uncalibrated multivariable-adjusted competing risk analyses do not find differences in tomato associations between aggressive and non-aggressive prostate cancers although power for aggressive cancers is limited.
CONCLUSION:
Consumption of canned and cooked tomatoes may reduce the risk of prostate cancer. These products contain more available lycopene. However, an observational study cannot exclude confounding by some unidentified, prostate cancer preventive factor.
KEYWORDS:
Cohort study; Lycopene; Prostate cancer; Seventh-day adventists; Tomatoes

Association of Leukocyte Telomere Length With Mortality Among Adult Participants in 3 Longitudinal Studies.
Arbeev KG, Verhulst S, Steenstrup T, Kark JD, Bagley O, Kooperberg C, Reiner AP, Hwang SJ, Levy D, Fitzpatrick AL, Christensen K, Yashin AI, Aviv A.
JAMA Netw Open. 2020 Feb 5;3(2):e200023. doi: 10.1001/jamanetworkopen.2020.0023.
PMID: 32101305
Abstract
IMPORTANCE:
Leukocyte telomere length (LTL) is a trait associated with risk of cardiovascular disease and cancer, the 2 major disease categories that largely define longevity in the United States. However, it remains unclear whether LTL is associated with the human life span.
OBJECTIVE:
To examine whether LTL is associated with the life span of contemporary humans.
DESIGN, SETTING, AND PARTICIPANTS:
This cohort study included 3259 adults of European ancestry from the Cardiovascular Health Study (CHS), Framingham Heart Study (FHS), and Women's Health Initiative (WHI). Leukocyte telomere length was measured in 1992 and 1997 in the CHS, from 1995 to 1998 in the FHS, and from 1993 to 1998 in the WHI. Data analysis was conducted from February 2017 to December 2019.
MAIN OUTCOMES AND MEASURES:
Death and LTL, measured by Southern blots of the terminal restriction fragments, were the main outcomes. Cause of death was adjudicated by end point committees.
RESULTS:
The analyzed sample included 3259 participants (2342 [71.9%] women), with a median (range) age of 69.0 (50.0-98.0) years at blood collection. The median (range) follow-up until death was 10.9 (0.2-23.0) years in CHS, 19.7 (3.4-23.0) years in FHS, and 16.6 (0.5-20.0) years in WHI. During follow-up, there were 1525 deaths (482 [31.6%] of cardiovascular disease; 373 [24.5%] of cancer, and 670 [43.9%] of other or unknown causes). Short LTL, expressed in residual LTL, was associated with increased mortality risk. Overall, the hazard ratio for all-cause mortality for a 1-kilobase decrease in LTL was 1.34 (95% CI, 1.21-1.47). This association was stronger for noncancer causes of death (cardiovascular death: hazard ratio, 1.28; 95% CI, 1.08-1.52; cancer: hazard ratio, 1.13; 95% CI, 0.93-1.36; and other causes: hazard ratio, 1.53; 95% CI, 1.32-1.77).
CONCLUSIONS AND RELEVANCE:
The results of this study indicate that LTL is associated with a natural life span limit in contemporary humans.

Longitudinal Maintenance of Cognitive Health in Centenarians in the 100-plus Study.
Beker N, Sikkes SAM, Hulsman M, Tesi N, van der Lee SJ, Scheltens P, Holstege H.
JAMA Netw Open. 2020 Feb 5;3(2):e200094. doi: 10.1001/jamanetworkopen.2020.0094.
PMID: 32101309
Abstract
IMPORTANCE:
Some individuals who reach ages beyond 100 years in good cognitive health may be resilient against risk factors associated with cognitive decline. Exploring the processes underlying resilience may contribute to the development of therapeutic strategies that help to maintain cognitive health while aging.
OBJECTIVE:
To identify individuals who escape cognitive decline until extreme ages and to investigate the prevalence of associated risk factors.
DESIGN, SETTING, AND PARTICIPANTS:
The 100-plus Study is a prospective observational cohort study of community-based Dutch centenarians enrolled between 2013 and 2019 who were visited annually until death or until participation was no longer possible. The centenarians self-reported their cognitive health, as confirmed by a proxy. Of the 1023 centenarians approached for study inclusion, 340 fulfilled the study criteria and were included in analyses. Data analysis was performed from April 2019 to December 2019.
MAIN OUTCOMES AND MEASURES:
Cognition was assessed using the Mini-Mental State Examination (MMSE). To identify centenarians who escape cognitive decline, this study investigated the association of baseline cognition with survivorship and cognitive trajectories for at least 2 years of follow-up using linear mixed models, adjusted for sex, age, and education. This study investigated the prevalence of apolipoprotein E (APOE) genotypes and cardiovascular disease as risk factors associated with cognitive decline.
RESULTS:
At baseline, the median age of 340 centenarians was 100.5 years (range, 100.0-108.2 years); 245 participants (72.1%) were female. The maximum survival estimate plateaued at 82% per year (95% CI, 77% to 87%) across centenarians who scored 26 to 30 points on the baseline MMSE (hazard ratio, 0.56; 95% CI, 0.42 to 0.75; P < .001), suggesting that an MMSE score of 26 or higher is representative of both cognitive and physical health. Among the 79 centenarians who were followed up for 2 years or longer, those with baseline MMSE score less than 26 experienced a decline in MMSE score of 1.68 points per year (95% CI, -2.45 to -0.92 points per year; P = .02), whereas centenarians with MMSE scores of 26 or higher at baseline experienced a decline of 0.71 point per year (95% CI, -1.08 to -0.35 points per year). For 73% of the centenarians with baseline MMSE scores of 26 or higher, no cognitive changes were observed, which often extended to ensuing years or until death. It is estimated that this group is representative of less than 10% of Dutch centenarians. In this group, 18.6% carried at least 1 APOE-ε4 allele, compared with 5.6% of the centenarians with lower and/or declining cognitive performance.
CONCLUSIONS AND RELEVANCE:
Most centenarians who scored 26 or higher on the MMSE at baseline maintained high levels of cognitive performance for at least 2 years, in some cases despite the presence of risk factors associated with cognitive decline. Investigation of this group might reveal the processes underlying resilience against risk factors associated with cognitive decline.

Edited February 28, 2020 by AlPater

[AlPater]

Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease.
Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KH, Summerbell CD, Worthington HV, Song F, Hooper L.
Cochrane Database Syst Rev. 2020 Feb 29;3:CD003177. doi: 10.1002/14651858.CD003177.pub5. Review.
PMID: 32114706
Abstract
BACKGROUND:
Omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3)), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha-linolenic acid (ALA)) may benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this.
OBJECTIVES:
To assess the effects of increased intake of fish- and plant-based omega-3 fats for all-cause mortality, cardiovascular events, adiposity and lipids.
SEARCH METHODS:
We searched CENTRAL, MEDLINE and Embase to February 2019, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to August 2019, with no language restrictions. We handsearched systematic review references and bibliographies and contacted trial authors.
SELECTION CRITERIA:
We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation or advice to increase LCn3 or ALA intake, or both, versus usual or lower intake.
DATA COLLECTION AND ANALYSIS:
Two review authors independently assessed trials for inclusion, extracted data and assessed validity. We performed separate random-effects meta-analysis for ALA and LCn3 interventions, and assessed dose-response relationships through meta-regression.
MAIN RESULTS:
We included 86 RCTs (162,796 participants) in this review update and found that 28 were at low summary risk of bias. Trials were of 12 to 88 months' duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most trials assessed LCn3 supplementation with capsules, but some used LCn3- or ALA-rich or enriched foods or dietary advice compared to placebo or usual diet. LCn3 doses ranged from 0.5 g a day to more than 5 g a day (19 RCTs gave at least 3 g LCn3 daily). Meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.93 to 1.01; 143,693 participants; 11,297 deaths in 45 RCTs; high-certainty evidence), cardiovascular mortality (RR 0.92, 95% CI 0.86 to 0.99; 117,837 participants; 5658 deaths in 29 RCTs; moderate-certainty evidence), cardiovascular events (RR 0.96, 95% CI 0.92 to 1.01; 140,482 participants; 17,619 people experienced events in 43 RCTs; high-certainty evidence), stroke (RR 1.02, 95% CI 0.94 to 1.12; 138,888 participants; 2850 strokes in 31 RCTs; moderate-certainty evidence) or arrhythmia (RR 0.99, 95% CI 0.92 to 1.06; 77,990 participants; 4586 people experienced arrhythmia in 30 RCTs; low-certainty evidence). Increasing LCn3 may slightly reduce coronary heart disease mortality (number needed to treat for an additional beneficial outcome (NNTB) 334, RR 0.90, 95% CI 0.81 to 1.00; 127,378 participants; 3598 coronary heart disease deaths in 24 RCTs, low-certainty evidence) and coronary heart disease events (NNTB 167, RR 0.91, 95% CI 0.85 to 0.97; 134,116 participants; 8791 people experienced coronary heart disease events in 32 RCTs, low-certainty evidence). Overall, effects did not differ by trial duration or LCn3 dose in pre-planned subgrouping or meta-regression. There is little evidence of effects of eating fish. Increasing ALA intake probably makes little or no difference to all-cause mortality (RR 1.01, 95% CI 0.84 to 1.20; 19,327 participants; 459 deaths in 5 RCTs, moderate-certainty evidence),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25; 18,619 participants; 219 cardiovascular deaths in 4 RCTs; moderate-certainty evidence), coronary heart disease mortality (RR 0.95, 95% CI 0.72 to 1.26; 18,353 participants; 193 coronary heart disease deaths in 3 RCTs; moderate-certainty evidence) and coronary heart disease events (RR 1.00, 95% CI 0.82 to 1.22; 19,061 participants; 397 coronary heart disease events in 4 RCTs; low-certainty evidence). However, increased ALA may slightly reduce risk of cardiovascular disease events (NNTB 500, RR 0.95, 95% CI 0.83 to 1.07; but RR 0.91, 95% CI 0.79 to 1.04 in RCTs at low summary risk of bias; 19,327 participants; 884 cardiovascular disease events in 5 RCTs; low-certainty evidence), and probably slightly reduces risk of arrhythmia (NNTB 91, RR 0.73, 95% CI 0.55 to 0.97; 4912 participants; 173 events in 2 RCTs; moderate-certainty evidence). Effects on stroke are unclear. Increasing LCn3 and ALA had little or no effect on serious adverse events, adiposity, lipids and blood pressure, except increasing LCn3 reduced triglycerides by ˜15% in a dose-dependent way (high-certainty evidence).
AUTHORS' CONCLUSIONS:
This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and low-certainty evidence suggests that increasing LCn3 slightly reduces risk of coronary heart disease mortality and events, and reduces serum triglycerides (evidence mainly from supplement trials). Increasing ALA slightly reduces risk of cardiovascular events and arrhythmia.

Drink types unmask the health risks associated with alcohol intake - Prospective evidence from the general population.
Schutte R, Papageorgiou M, Najlah M, Huisman HW, Ricci C, Zhang J, Milner N, Schutte AE.
Clin Nutr. 2020 Feb 15. pii: S0261-5614(20)30057-1. doi: 10.1016/j.clnu.2020.02.009. [Epub ahead of print]
PMID: 32111522
Abstract
BACKGROUND & AIMS:
Uncertainty still exists on the impact of low to moderate consumption of different drink types on population health. We therefore investigated the associations of different drink types in the form of beer/cider, champagne/white wine, red wine and spirits with various health outcomes.
METHODS:
Over 500,000 participants were recruited to the UK Biobank cohort. Alcohol consumption was self-reported as pints beer/cider, glasses champagne/white wine, glasses of red wine, and measures of spirits per week. We followed health outcomes for a median of 7.02 years and reported all-cause mortality, cardiovascular events, ischemic heart disease, cerebrovascular events, and cancer.
RESULTS:
In continuous analysis after excluding non-drinkers, beer/cider and spirits intake associated with an increased risk for all-cause mortality (beer/cider: hazard ratio, 1.56; 95% confidence interval, 1.45-1.68; spirits: 1.47; 1.35-1.60), cardiovascular events (beer/cider: 1.25; 1.17-1.33; spirits: 1.25; 1.16-1.36), ischemic heart disease (beer/cider:1.12; 0.99-1.26 [P = 0.056]; spirits: 1.17; 1.02-1.35), cerebrovascular disease (beer/cider: 1.63; 1.32-2.02; spirits: 1.59; 1.25-2.02) and cancer (beer/cider: 1.14; 1.05-1.24; spirits: 1.14; 1.03-1.26), while both champagne/white wine and red wine associated with a decreased risk for ischemic heart disease only (champagne/white wine: 0.84; 0.72-0.98; red wine: 0.88; 0.77-0.99).
CONCLUSIONS:
Our findings do not support the notion that alcohol from any drink type is beneficial to health. Consuming low levels of beer/cider and spirits already associated with an increased risk for all health outcomes, while wine showed opposite protective relationships only with ischemic heart disease.
KEYWORDS:
Alcohol; Drink types; General population; Health outcomes

The road ahead for health and lifespan interventions.
Gonzalez-Freire M, Diaz-Ruiz A, Hauser D, Martinez-Romero J, Ferrucci L, Bernier M, de Cabo R.
Ageing Res Rev. 2020 Feb 25:101037. doi: 10.1016/j.arr.2020.101037. [Epub ahead of print] Review.
PMID: 32109604
https://www.sciencedirect.com/science/article/pii/S1568163718302435?via%3Dihub
Abstract
Aging is a modifiable risk factor for most chronic diseases and an inevitable process in humans. The development of pharmacological interventions aimed at delaying or preventing the onset of chronic conditions and other age-related diseases has been at the forefront of the aging field. Preclinical findings have demonstrated that species, sex and strain confer significant heterogeneity on reaching the desired health- and lifespan-promoting pharmacological responses in model organisms. Translating the safety and efficacy of these interventions to humans and the lack of reliable biomarkers that serve as predictors of health outcomes remain a challenge. Here, we will survey current pharmacological interventions that promote lifespan extension and/or increased healthspan in animals and humans, and review the various anti-aging interventions selected for inclusion in the NIA's Interventions Testing Program as well as the ClinicalTrials.gov database that target aging or age-related diseases in humans.
KEYWORDS:
aging; frailty; healthspan; lifespan; longevity; translation; “anti-aging”

[AlPater]

Intake of starch and sugars and total and cause-specific mortality in a Japanese community: the Takayama Study.
Nagata C, Wada K, Yamakawa M, Konishi K, Goto Y, Koda S, Mizuta F, Uji T.
Br J Nutr. 2019 Oct 14;122(7):820-828. doi: 10.1017/S0007114519001661.
PMID: 32124712
Abstract
Studies on the intake of different types of carbohydrates and long-term mortality are sparse. We examined the association of starch, total and each type of sugar and free sugars with the risk of total and cause-specific mortality in a cohort of the general population in Japan. Study subjects were 29 079 residents from the Takayama Study, Japan, who responded to a self-administered questionnaire in 1992. Diet was assessed by a validated FFQ at the baseline. Mortality was ascertained during 16 years of follow-up. We noted 2901 deaths (974 cancer related and 775 cardiovascular related) in men and 2438 death (646 cancer related and 903 cardiovascular related) in women. In men, intake of starch was inversely associated with total mortality after controlling for covariates (hazard ratio (HR) for the highest quartile v. lowest quartile: 0·71; 95 % CI 0·60, 0·84; Ptrend < 0·001). Intakes of total sugars, glucose, fructose, sucrose, maltose and free and naturally occurring sugars were significantly positively associated with total mortality in men (HR for the highest v. lowest quartile of total sugar: 1·27; 95 % CI 1·12, 1·45; Ptrend < 0·0001). Similar relations were observed for cardiovascular mortality and non-cancer, non-cardiovascular mortality in men. In women, there was no significant association between any type of carbohydrates and mortality except that intake of free sugars was significantly positively associated with total and non-cancer, non-cardiovascular mortality. Data suggest that the high intake of starch reduces mortality, whereas the high intake of sugars, including glucose, fructose and sucrose, increases mortality in Japanese men.
KEYWORDS:
Cohort studies; Fructose; Japanese; Mortality; Starches; Sucrose; Sugars

The Association between Health Insurance and All-Cause, Cardiovascular Disease, Cancer and Cause-Specific Mortality: A Prospective Cohort Study.
Song L, Wang Y, Chen B, Yang T, Zhang W, Wang Y.
Int J Environ Res Public Health. 2020 Feb 27;17(5). pii: E1525. doi: 10.3390/ijerph17051525.
PMID: 32120888
Abstract
The purpose of this study was to evaluate the association of insurance status with all-cause and cause-specific mortality. A total of 390,881 participants, aged 18-64 years and interviewed from 1997 to 2013 were eligible for a mortality follow-up in December 31, 2015. Cox proportional hazards models were used to calculate the hazards ratios (HR) and 95% confidence intervals (CI) to determine the association between insurance status and all-cause and cause-specific mortality. The sample group cumulatively aged 4.22 million years before their follow-ups, with a mean follow-up of 10.4 years, and a total of 22,852 all-cause deaths. In fully adjusted models, private insurance was significantly associated with a 17% decreased risk of mortality (HR = 0.83; 95% CI = 0.80-0.87), but public insurance was associated with a 21% increased risk of mortality (HR = 1.21; 95% CI = 1.15-1.27). Compared to noninsurance, private coverage was associated with about 21% lower CVD mortality risk (HR = 0.79, 95% CI = 0.70-0.89). In addition, public insurance was associated with increased mortality risk of kidney disease, diabetes and CLRD, compared with noninsurance, respectively. This study supports the current evidence for the relationship between private insurance and decreased mortality risk. In addition, our results show that public insurance is associated with an increased risk of mortality.
KEYWORDS:
cohort; health insurance; mortality

Delivery method matters: omega-3 supplementation by restricted feeding period and oral gavage has a distinct impact on corticosterone secretion and anxious behavior in adolescent rats.
Raymond J, Morin A, Plamondon H.
Nutr Neurosci. 2020 Mar 3:1-11. doi: 10.1080/1028415X.2020.1733813. [Epub ahead of print]
PMID: 32124679
Abstract
Objectives: Oral gavage and time-restricted feeding are common delivery methods for dietary supplementation to rodents. However, the stress associated with selected feeding regimens could represent a confounding variable. In rodents, the adolescence period is particularly vulnerable to stressful events, in part related to ongoing maturation of the brain. In this context, omega-3 dietary supplementation has shown beneficial effects on neuronal growth, cognitive performance and stress regulation, while high-fat diet (HVF) has been associated with enhanced stress and anxiety. Therefore, this study has two aims: (1) evaluate the influence of 21-day supplementation with soybean oil (control group; CSO), fish oil (FO) or hydrogenated vegetable fat (HVF) fatty acids (FA) during the adolescence period on corticosterone secretion and anxiety-like behavior and, (2) compare the impact of dietary supplementation using oral gavage or time-limited feeding on these measures.Methods: Oral gavage or restricted feeding were used to daily feed adolescent rats (PND28-47; n = 49). On supplementation days 1, 7, 14 and 21, droplets of blood were collected for corticosterone (CORT) assessments. The Open Field (OFT) and the Elevated-Plus Maze (EPM) tests served to assess anxiety-like behavior on PND50.Results: Our findings indicate increased CORT secretion in restricted-(R) compared to gavage-fed animals on DAY7 and DAY14, suggesting heightened HPA-axis reactivity. Notably, CORT secretion diminished in FO-R-rats (DAY21), suggesting improved coping/adjustment. Consistent with CORT assessments, findings in the OFT and EPM supported attenuated anxiety in gavage versus restricted groups. FO and CSO supplementation reduced anxiety compared to HVF intake.Conclusions: Our findings uncover a significant impact of feeding methods on anxiety-like behavior and physiological stress response in rodents, supporting oral gavage as a less stressful option during the adolescent developmental stage. Supplement-specific effects on CORT secretion further indicated an influence of fish oil in regulating the stress response.
KEYWORDS:
Omega-3; anxiety-like behavior; corticosterone; fish oil; gavage; high-fat diet; stress response

Energy Restriction Enhances Adult Hippocampal Neurogenesis-Associated Memory after Four Weeks in an Adult Human Population with Central Obesity; a Randomized Controlled Trial.
Kim C, Pinto AM, Bordoli C, Buckner LP, Kaplan PC, Del Arenal IM, Jeffcock EJ, Hall WL, Thuret S.
Nutrients. 2020 Feb 28;12(3). pii: E638. doi: 10.3390/nu12030638.
PMID: 32121111
Abstract
Adult neurogenesis, the generation of new neurons throughout life, occurs in the subventricular zone of the dentate gyrus in the human hippocampal formation. It has been shown in rodents that adult hippocampal neurogenesis is needed for pattern separation, the ability to differentially encode small changes derived from similar inputs, and recognition memory, as well as the ability to recognize previously encountered stimuli. Improved hippocampus-dependent cognition and cellular readouts of adult hippocampal neurogenesis have been reported in daily energy restricted and intermittent fasting adult mice. Evidence that nutrition can significantly affect brain structure and function is increasing substantially. This randomized intervention study investigated the effects of intermittent and continuous energy restriction on human hippocampal neurogenesis-related cognition, which has not been reported previously. Pattern separation and recognition memory were measured in 43 individuals with central obesity aged 35-75 years, before and after a four-week dietary intervention using the mnemonic similarity task. Both groups significantly improved pattern separation (P = 0.0005), but only the intermittent energy restriction group had a significant deterioration in recognition memory. There were no significant differences in cognitive improvement between the two diets. This is the first human study to investigate the association between energy restriction with neurogenesis-associated cognitive function. Energy restriction may enhance hippocampus-dependent memory and could benefit those in an ageing population with declining cognition. This study was registered on ClinicalTrials.gov (NCT02679989) on 11 February 2016.
KEYWORDS:
adult hippocampal neurogenesis; ageing; cognition; energy restriction; intermittent fasting; pattern separation; randomized controlled trial; recognition memory

Diet modulates brain network stability, a biomarker for brain aging, in young adults.
Mujica-Parodi LR, Amgalan A, Sultan SF, Antal B, Sun X, Skiena S, Lithen A, Adra N, Ratai EM, Weistuch C, Govindarajan ST, Strey HH, Dill KA, Stufflebeam SM, Veech RL, Clarke K.
Proc Natl Acad Sci U S A. 2020 Mar 3. pii: 201913042. doi: 10.1073/pnas.1913042117. [Epub ahead of print]
PMID: 32127481
Abstract
Epidemiological studies suggest that insulin resistance accelerates progression of age-based cognitive impairment, which neuroimaging has linked to brain glucose hypometabolism. As cellular inputs, ketones increase Gibbs free energy change for ATP by 27% compared to glucose. Here we test whether dietary changes are capable of modulating sustained functional communication between brain regions (network stability) by changing their predominant dietary fuel from glucose to ketones. We first established network stability as a biomarker for brain aging using two large-scale (n = 292, ages 20 to 85 y; n = 636, ages 18 to 88 y) 3 T functional MRI (fMRI) datasets. To determine whether diet can influence brain network stability, we additionally scanned 42 adults, age < 50 y, using ultrahigh-field (7 T) ultrafast (802 ms) fMRI optimized for single-participant-level detection sensitivity. One cohort was scanned under standard diet, overnight fasting, and ketogenic diet conditions. To isolate the impact of fuel type, an independent overnight fasted cohort was scanned before and after administration of a calorie-matched glucose and exogenous ketone ester (d-β-hydroxybutyrate) bolus. Across the life span, brain network destabilization correlated with decreased brain activity and cognitive acuity. Effects emerged at 47 y, with the most rapid degeneration occurring at 60 y. Networks were destabilized by glucose and stabilized by ketones, irrespective of whether ketosis was achieved with a ketogenic diet or exogenous ketone ester. Together, our results suggest that brain network destabilization may reflect early signs of hypometabolism, associated with dementia. Dietary interventions resulting in ketone utilization increase available energy and thus may show potential in protecting the aging brain.
KEYWORDS:
beta-hydroxybutyrate; brain; glucose; ketone; neural

Chronic and acute effects of cocoa products intake on arterial stiffness and platelet count and function: A systematic review and dose-response Meta-analysis of randomized clinical trials.
Jafari Azad B, Daneshzad E, Meysamie AP, Koohdani F.
Crit Rev Food Sci Nutr. 2020 Mar 4:1-23. doi: 10.1080/10408398.2020.1733484. [Epub ahead of print]
PMID: 32126803
Abstract
The findings of trials investigating the effect of cocoa products consumption on vascular stiffness and platelet are controversial. The aim of this study is to summarize the findings on the acute and chronic effects of different forms of cocoa on the risk factors of cardiovascular disease. We searched SCOPUS, Pub Med and Web of Science from inception to Jan 2020. Finally, the random-effect model was used to report the pooled effect sizes. Results are expressed as weighted mean difference (WMD) with 95% confidence intervals (CI).Overall, 41 trials were included, of which only 14 studies met the eligibility criteria for analysis, including 11 long-term RCTs (more than a week was considered as a chronic phase) and 7 short-term RCTs (less than a week was considered as an acute phase). According to the result of 11 long-term RCTs, cocoa products had a negative significant effect on pulse wave velocity; PWV (WMD: -0.33 m/s, P < 0.0001), Augmentation index; AIx (WMD: -4.50%, P = 0.001) but had no significant effect on platelet count (WMD: -10.41 109/L, P = 0.053). Also, according to the results of 7 short-term RCTs, cocoa products had a negative significant effect on PWV (WMD: -0.27 m/s, P = 0.019), AIx (WMD: -4.47%, P = 0.003).Current study indicated the beneficial effect of acute and chronic consumption of cocoa-based products ingestion on platelet function and arterial stiffness in healthy adult regardless of age especially in male and for consumption (≤4 weeks) in the chronic intake and (≤120 minutes) in acute intake, but did not affect on platelet count. However, further studies are required to shed light on this issue.
KEYWORDS:
Arterial stiffness; Chocolate; Cocoa; Meta-analysis; Platelet

[AlPater]

Dietary polyunsaturated fat intake in relation to head and neck, esophageal, and gastric cancer incidence in the NIH-AARP Diet and Health Study.
Zamani SA, McClain KM, Graubard BI, Liao LM, Abnet CC, Cook MB, Petrick JL.
Am J Epidemiol. 2020 Mar 6. pii: kwaa024. doi: 10.1093/aje/kwaa024. [Epub ahead of print]
PMID: 32141493
Abstract
n-3 polyunsaturated fatty acids (PUFAs) express anti-inflammatory properties and prevent tumor progression. Conversely, n-6 PUFAs exhibit carcinogenic properties. Recent epidemiologic studies have examined the association of fish with upper gastrointestinal cancer risk, but the associations with n-3 and n-6 PUFA subtypes remain unclear. Utilizing the NIH-AARP Diet and Health Study (1995-2011), we prospectively investigated the associations of PUFA subtypes, ratios, and fish with the incidence of head and neck (HNC, n=2,453), esophageal (n=855 adenocarcinoma, EA, and n=267 squamous cell carcinoma, ESCC), and gastric (n=603 cardia, GCA, and n=631 non-cardia, NCGA) cancers among 468,952 participants (median follow-up 15.5 years). A food frequency questionnaire assessed diet. Multivariable-adjusted HRs and 95% CIs were estimated using Cox proportional hazards regression. A Benjamini-Hochberg (BH) procedure was used for false-discovery control. Long-chain n-3 PUFAs were associated with a 20% decreased HNC and EA risk (quintile5vs.1 HR=0.81, 95% CI: 0.71-0.92, BH-adjusted P-trend=0.001 and HR=0.79, 95% CI: 0.64-0.98, BH-adjusted P-trend=0.1, respectively). Similar associations were observed for non-fried fish, but only for high intake. Further, the ratio of long-chain n3:n6 was associated with a decreased HNC and EA risk. No consistent associations were observed for gastric cancer. Our results indicate that dietary PUFA and non-fried fish intake is associated with lower HNC and EA risk.
KEYWORDS:
esophageal cancer; food frequency questionnaire; gastric cancer; head and neck cancer; polyunsaturated fatty acids

The effects of testosterone on bone health in males with testosterone deficiency: a systematic review and meta-analysis.
Zhang Z, Kang D, Li H.
BMC Endocr Disord. 2020 Mar 7;20(1):33. doi: 10.1186/s12902-020-0509-6.
PMID: 32145741
Abstract
BACKGROUND:
Testosterone deficiency (TD) may induce a series of clinical symptoms. Studies have shown that testosterone supplementation may prevent these unfavourable symptoms and improve patients' quality of life. Given the conflicting findings across studies, this systematic review aims to evaluate the effects and risks associated with testosterone supplementation in middle-aged or aging males with TD.
METHODS:
Electronic databases (MEDLINE, EMBASE, PubMed, and Cochrane. Library were searched to December 2019. The risk of bias of individual included studies and the quality of the aggregate evidence were assessed using the GRADE approach. Our primary outcome was bone mineral density (BMD). Meta-analyses were performed. This systematic review was reported according to the PRISMA statement.
RESULTS:
A total of 52 randomized controlled trials (RCTs) were included. When compared with placebo, testosterone supplementation did not increase total BMD (short-term: 1081 participants, MD - 0.01 g/cm2, 95% CI - 0.02 g/cm2 to 0.01 g/cm2; long-term: 156 participants, MD 0.04 g/cm2, 95% CI - 0.07 g/cm2 to 0.14 g/cm2), lumbar spine, hip, or femur neck BMD. Furthermore, testosterone supplementation did not decrease the risk of falling or fracture. Lastly, it was found that testosterone supplementation did not increase the risk of cardiovascular events (1374 participants, RR 1.28, 95% CI 0.62 to 2.64), all-cause mortality (729 participants, RR 0.55, 95% CI 0.29 to 1.04), or prostatic events. However, testosterone supplementation may improve sexual function and quality of life (1328 participants, MD -1.32, 95% CI - 2.11 to - 0.52).
CONCLUSIONS:
The effect of testosterone supplementation on BMD and the risk of falls or fracture remains inconclusive. However, supplementation may benefit patients in the areas of sexual function and quality of life without increasing the risk of cardiovascular events, all-cause mortality, or prostatic events. RCTs with a longer follow-up period are still required.
KEYWORDS:
Aging; Males; Systematic review; Testosterone; Testosterone deficiency

Association of sulfur amino acid consumption with cardiometabolic risk factors: Cross-sectional findings from NHANES III.
Dong Z, Gao X, Chinchilli VM, Sinha R, Muscat J, Winkels RM, Richie JP Jr.
EClinicalMedicine. 2020 Feb 3;19:100248. doi: 10.1016/j.eclinm.2019.100248. eCollection 2020 Feb.
PMID: 32140669
https://www.thelancet.com/pdfs/journals/eclinm/PIIS2589-5370(19)30257-3.pdf
Abstract
BACKGROUND:
An average adult American consumes sulfur amino acids (SAA) at levels far above the Estimated Average Requirement (EAR) and recent preclinical data suggest that higher levels of SAA intake may be associated with a variety of aging-related chronic diseases. However, there are little data regarding the relationship between SAA intake and chronic disease risk in humans. The aim of this study was to examine the associations between consumption of SAA and risk factors for cardiometabolic diseases.
METHODS:
The sample included 11,576 adult participants of the Third National Examination and Nutritional Health Survey (NHANES III) Study (1988-1994). The primary outcome was cardiometabolic disease risk score (composite risk factor based on blood cholesterol, triglycerides, HDL, C-reactive protein (CRP), uric acid, glucose, blood urea nitrogen (BUN), glycated hemoglobin, insulin, and eGFR). Group differences in risk score by quintiles of energy-adjusted total SAA, methionine (Met), and cysteine (Cys) intake were determined by multiple linear regression after adjusting for age, sex, BMI, smoking, alcohol intake, and dietary factors. We further examined for associations between SAA intake and individual risk factors.
FINDINGS:
Mean SAA consumption was > 2.5-fold higher than the EAR. After multivariable adjustment, higher intake of SAA, Met, and Cys were associated with significant increases in composite cardiometabolic disease risk scores, independent of protein intake, and with several individual risk factors including serum cholesterol, glucose, uric acid, BUN, and insulin and glycated hemoglobin (p < 0.01).
INTERPRETATION:
Overall, our findings suggest that diets lower in SAA (close to the EAR) are associated with reduced risk for cardiometabolic diseases. Low SAA dietary patterns rely on plant-derived protein sources over meat derived foods. Given the high intake of SAA among most adults, our findings may have important public health implications for chronic disease prevention.
KEYWORDS:
BUN, blood urea nitrogen; CRP, C-reactive protein; Cardiometabolic diseases; Cys, cysteine; Cysteine; Diabetes; Dietary sulfur amino acids; EAR, estimated average requirement; IR, insulin resistance; MEC, mobile examination center; Met, methionine; Methionine; NHANES III, Third National Examination and Nutritional Health Survey; RDA, recommended dietary allowance; SAA, sulfur amino acids; SAAR, sulfur amino acid restriction; Sulfur amino acids restriction; eGFR, estimated glomerular filtration rate

Caffeinated coffee consumption and risk of atrial fibrillation in two Spanish cohorts.
Bazal P, Gea A, Navarro AM, Salas-Salvadó J, Corella D, Alonso-Gómez A, Fitó M, Muñoz-Bravo C, Estruch R, Fiol M, Lapetra J, Serra-Majem L, Ros E, Rekondo J, Muñoz MA, Basora J, Sorlí JV, Toledo E, Martínez-González MA, Ruiz-Canela M.
Eur J Prev Cardiol. 2020 Mar 4:2047487320909065. doi: 10.1177/2047487320909065. [Epub ahead of print]
PMID: 32131628
Abstract
AIMS:
The association between caffeinated coffee consumption and atrial fibrillation remains unclear. Recent studies suggest an inverse association only between a moderate caffeinated coffee consumption and atrial fibrillation, but others have reported no association. The aim of our study was to prospectively assess the association between caffeinated coffee consumption and atrial fibrillation in two Spanish cohorts, one of adults from a general population and another of elderly participants at high cardiovascular risk.
METHODS AND RESULTS:
We included 18,983 and 6479 participants from the 'Seguimiento Universidad de Navarra' (SUN) and 'Prevención con Dieta Mediterránea' (PREDIMED) cohorts, respectively. Participants were classified according to their caffeinated coffee consumption in three groups: ≤3 cups/month, 1-7 cups/week, and >1 cup/day. We identified 97 atrial fibrillation cases after a median follow-up of 10.3 years (interquartile range 6.5-13.5), in the SUN cohort and 250 cases after 4.4 years median follow-up (interquartile range 2.8-5.8) in the PREDIMED study. No significant associations were observed in the SUN cohort although a J-shaped association was suggested. A significant inverse association between the intermediate category of caffeinated coffee consumption (1-7 cups/week) and atrial fibrillation was observed in PREDIMED participants with a multivariable-adjusted hazard ratio = 0.53 (95% confidence interval 0.36-0.79) when compared with participants who did not consume caffeinated coffee or did it only occasionally. No association was found for higher levels of caffeinated coffee consumption (>1 cup per day), hazard ratio = 0.79 (95% confidence interval 0.49-1.28). In the meta-analysis of both PREDIMED and SUN studies, the hazard ratio for intermediate consumption of caffeinated coffee was 0.60 (95% confidence interval 0.44-0.82) without evidence of heterogeneity. Similar findings were found for the association between caffeine intake and atrial fibrillation risk.
CONCLUSION:
Intermediate levels of caffeinated coffee consumption (1-7 cups/week) were associated with a reduction in atrial fibrillation risk in two prospective Mediterranean cohorts.
KEYWORDS:
Atrial fibrillation; Mediterranean diet; caffeine; coffee

Effects of garlic supplementation on liver enzymes: A systematic review and meta-analysis of randomized controlled trials.
Panjeshahin A, Mollahosseini M, Panbehkar-Jouybari M, Kaviani M, Mirzavandi F, Hosseinzadeh M.
Phytother Res. 2020 Mar 5. doi: 10.1002/ptr.6659. [Epub ahead of print] Review.
PMID: 32135032
Abstract
Current evidence on the beneficial effects of garlic on liver enzymes is contradictory. Therefore, the aim of this systematic review and meta-analysis is to evaluate the effect of garlic supplementation on human liver enzymes, such as Alanine Transaminase (ALT/SGPT) and Aspartate Transaminase (AST/SGOT). To collect the required data, PubMed, Scopus, ISI Web of Science, and Google scholar databases were systematically searched from inception to June 2019. A meta-analysis was conducted using the random-effects model to evaluate the effects of garlic supplementation on ALT and AST levels. The Cochran's Q-test and inconsistency index were also used to evaluate heterogeneity among the studies. Among a total of 15,514 identified articles, six studies (containing 301 participants) met the inclusion criteria. Results of the meta-analysis showed that garlic supplementation significantly decreased AST level (Hedges' g = -0.36, 95% confidence interval [CI]: -0.72, -0.004, p = .047); whereas, it had no significant effect on ALT level (Hedges' g = -0.22, 95% CI: -0.64, 0.20, p = .310). Results showed that garlic supplementation reduced AST levels significantly; however, had no significant effect on ALT levels. Further studies are still needed to confirm the results.
KEYWORDS:
ALT; AST; garlic; liver enzyme; meta-analysis; systematic review

Omega-3 and -6 Fatty Acid Intake and Colorectal Cancer Risk in Swedish Women's Lifestyle and Health Cohort.
Shin A, Cho S, Sandin S, Lof M, Oh MY, Weiderpass E.
Cancer Res Treat. 2020 Mar 6. doi: 10.4143/crt.2019.550. [Epub ahead of print]
PMID: 32138465
Abstract
PURPOSE:
We aimed to assess the association between the dietary intake of fish-derived omega-3 polyunsaturated fatty acids and the risk of colorectal cancer among Swedish women.
MATERIALS AND METHODS:
A total of 48,233 women with information on dietary intake were included in the analysis. Participants were followed for incident colorectal cancer until 31 December 2012. Cox proportional hazard models were used to assess the association between baseline fatty acid intake and colorectal cancer risk. All analyses were stratified by colon and rectal cancers.
RESULTS:
During a median of 21.3 years of follow-up, a total of 344 colorectal cancer cases were ascertained. Although there was no overall association between omega-3 fatty acid intake and colorectal cancer risk, high intake of fish-derived docosahexaenoic acid was associated with reduced risk of rectal cancer (hazard ratios for the third and the highest quartiles were 0.59 (95% confidence interval [CI], 0.37 to 0.96) and 0.62 (95% CI, 0.39 to 0.98), respectively).
CONCLUSION:
In conclusion, we found only limited support for an association between omega-3 polyunsaturated fatty acids and colorectal cancer in a large Swedish cohort of middle-aged women.

Egg consumption and risk of cardiovascular disease: three large prospective US cohort studies, systematic review, and updated meta-analysis.
Drouin-Chartier JP, Chen S, Li Y, Schwab AL, Stampfer MJ, Sacks FM, Rosner B, Willett WC, Hu FB, Bhupathiraju SN.
BMJ. 2020 Mar 4;368:m513. doi: 10.1136/bmj.m513.
PMID: 32132002 Free Article
Abstract
OBJECTIVE:
To evaluate the association between egg intake and cardiovascular disease risk among women and men in the United States, and to conduct a meta-analysis of prospective cohort studies.
DESIGN:
Prospective cohort study, and a systematic review and meta-analysis of prospective cohort studies.
SETTING:
Nurses' Health Study (NHS, 1980-2012), NHS II (1991-2013), Health Professionals' Follow-Up Study (HPFS, 1986-2012).
PARTICIPANTS:
Cohort analyses included 83 349 women from NHS, 90 214 women from NHS II, and 42 055 men from HPFS who were free of cardiovascular disease, type 2 diabetes, and cancer at baseline.
MAIN OUTCOME MEASURES:
Incident cardiovascular disease, which included non-fatal myocardial infarction, fatal coronary heart disease, and stroke.
RESULTS:
Over up to 32 years of follow-up (>5.54 million person years), 14 806 participants with incident cardiovascular disease were identified in the three cohorts. Participants with a higher egg intake had a higher body mass index, were less likely to be treated with statins, and consumed more red meats. Most people consumed between one and less than five eggs per week. In the pooled multivariable analysis, consumption of at least one egg per day was not associated with incident cardiovascular disease risk after adjustment for updated lifestyle and dietary factors associated with egg intake (hazard ratio for at least one egg per day v less than one egg per month 0.93, 95% confidence interval 0.82 to 1.05). In the updated meta-analysis of prospective cohort studies (33 risk estimates, 1 720 108 participants, 139 195 cardiovascular disease events), an increase of one egg per day was not associated with cardiovascular disease risk (pooled relative risk 0.98, 95% confidence interval 0.93 to 1.03, I2=62.3%). Results were similar for coronary heart disease (21 risk estimates, 1 411 261 participants, 59 713 coronary heart disease events; 0.96, 0.91 to 1.03, I2=38.2%), and stroke (22 risk estimates, 1 059 315 participants, 53 617 stroke events; 0.99, 0.91 to 1.07, I2=71.5%). In analyses stratified by geographical location (P for interaction=0.07), no association was found between egg consumption and cardiovascular disease risk among US cohorts (1.01, 0.96 to 1.06, I2=30.8%) or European cohorts (1.05, 0.92 to 1.19, I2=64.7%), but an inverse association was seen in Asian cohorts (0.92, 0.85 to 0.99, I2=44.8%).
CONCLUSIONS:
Results from the three cohorts and from the updated meta-analysis show that moderate egg consumption (up to one egg per day) is not associated with cardiovascular disease risk overall, and is associated with potentially lower cardiovascular disease risk in Asian populations.

Blood pressure in frail older adults: associations with cardiovascular outcomes and all-cause mortality.
Masoli JAH, Delgado J, Pilling L, Strain D, Melzer D.
Age Ageing. 2020 Mar 5. pii: afaa028. doi: 10.1093/ageing/afaa028. [Epub ahead of print]
PMID: 32133525
Abstract
BACKGROUND:
Blood pressure (BP) management in frail older people is challenging. An randomised controlled trial of largely non-frail older people found cardiovascular and mortality benefit with systolic (S) BP target <120 mmHg. However, all-cause mortality by attained BP in routine care in frail adults aged above 75 is unclear.
OBJECTIVES:
To estimate observational associations between baseline BP and mortality/cardiovascular outcomes in a primary-care population aged above 75, stratified by frailty.
METHODS:
Prospective observational analysis using electronic health records (clinical practice research datalink, n = 415,980). We tested BP associations with cardiovascular events and mortality using competing and Cox proportional-hazards models respectively (follow-up ≤10 years), stratified by baseline electronic frailty index (eFI: fit (non-frail), mild, moderate, severe frailty), with sensitivity analyses on co-morbidity, cardiovascular risk and BP trajectory.
RESULTS:
Risks of cardiovascular outcomes increased with SBPs >150 mmHg. Associations with mortality varied between non-frail <85 and frail 75-84-year-olds and all above 85 years. SBPs above the 130-139-mmHg reference were associated with lower mortality risk, particularly in moderate to severe frailty or above 85 years (e.g. 75-84 years: 150-159 mmHg Hazard Ratio (HR) mortality compared to 130-139: non-frail HR = 0.94, 0.92-0.97; moderate/severe frailty HR = 0.84, 0.77-0.92). SBP <130 mmHg and Diastolic(D)BP <80 mmHg were consistently associated with excess mortality, independent of BP trajectory toward the end of life.
CONCLUSIONS:
In representative primary-care patients aged ≥75, BP <130/80 was associated with excess mortality. Hypertension was not associated with increased mortality at ages above 85 or at ages 75-84 with moderate/severe frailty, perhaps due to complexities of co-existing morbidities. The priority given to aggressive BP reduction in frail older people requires further evaluation.
KEYWORDS:
blood pressure; frailty; hypertension

Associations of habitual fish oil supplementation with cardiovascular outcomes and all cause mortality: evidence from a large population based cohort study.
Li ZH, Zhong WF, Liu S, Kraus VB, Zhang YJ, Gao X, Lv YB, Shen D, Zhang XR, Zhang PD, Huang QM, Chen Q, Wu XB, Shi XM, Wang D, Mao C.
BMJ. 2020 Mar 4;368:m456. doi: 10.1136/bmj.m456.
PMID: 32131999 Free Article
Abstract
OBJECTIVES:
To evaluate the associations of habitual fish oil supplementation with cardiovascular disease (CVD) and mortality in a large prospective cohort.
DESIGN:
Population based, prospective cohort study.
SETTING:
UK Biobank.
PARTICIPANTS:
A total of 427 678 men and women aged between 40 and 69 who had no CVD or cancer at baseline were enrolled between 2006 and 2010 and followed up to the end of 2018.
MAIN EXPOSURE:
All participants answered questions on the habitual use of supplements, including fish oil.
MAIN OUTCOME MEASURES:
All cause mortality, CVD mortality, and CVD events.
RESULTS:
At baseline, 133 438 (31.2%) of the 427 678 participants reported habitual use of fish oil supplements. The multivariable adjusted hazard ratios for habitual users of fish oil versus non-users were 0.87 (95% confidence interval 0.83 to 0.90) for all cause mortality, 0.84 (0.78 to 0.91) for CVD mortality, and 0.93 (0.90 to 0.96) for incident CVD events. For CVD events, the association seemed to be stronger among those with prevalent hypertension (P for interaction=0.005).
CONCLUSIONS:
Habitual use of fish oil seems to be associated with a lower risk of all cause and CVD mortality and to provide a marginal benefit against CVD events among the general population.

The anti-osteoporostic effects of Natto on Bone Mineral Density in Perimenopausal Women.
Liu Y, He Y, Baorong H, Lingbo K.
Curr Med Chem. 2020 Mar 6. doi: 10.2174/0929867327666200306123140. [Epub ahead of print]
PMID: 32141414
Abstract
OBJECTIVE:
To conduct a systematic review and meta-analysis of prospective studies investigating the improvement effects of natto on bone mineral density in perimenopausal women. Design Systematic review and meta-analysis.Data sources PubMed, EMBASE and Cochrane database searched up to February 2019.
REVIEW METHODS:
This study was carried out according to the PRISMA guidelines10 for systematic reviews. The protocol of the review was registered in the PROSPERO registry (CRD42019133183).
RESULTS:
The review identified 3 unique prospective studies comprising 1658 non-overlapping participants. Meta-analysis showed that natto could significantly improve lumbar bone mineral density (BMD) (P=0.002, WMD=0.26). 95% CI:0.09-0.43) in cohort studies. However, the randomized controlled study showed no statistical difference between the two (P=0.31, WMD=0.05; 95% CI:-0.05-0.15). In addition natto significantly improve the BMD of femoral neck in cohort study and randomized control study (P=0.03, WMD=0.42). 95% CI:0.05-0.79, I2= 72%); (P < 0.0001, WMD=0.16; 95% CI:0.08-0.24), respectively. However, all studies demonstrated that natto has no improvement effects on hip joint BMD. In that the cohort study showed no statistical significance between the natto intake group and the control group (P=0.21, WMD=0.10). 95% CI:-0.06-0.25, I2= 18%) and the randomized controlled study also showed no statistical significance between the natto intake group and the control group (P=0.09, WMD=-0.06). 95% CI:-0.13-0.01).
CONCLUSION:
Through systematic review and meta-analysis for prospective studies of natto on BMD, we could speculate the dietary intake natto has the improvement effects on BMD of the femoral neck, but not the hip joint. Such results may be related to differences in the anatomical structure of tissues. The results of the RCT study and cohort study on the lumbar spine were not the same, which may be related to the fact that participants in the RCT study were Caucasian and participants in the cohort study were Asian. Therefore, more large-sample and high-quality RCT studies are needed to further clarify the improvement effect of natto on osteoporosis.
KEYWORDS:
Natto; Osteoporosis; bone mineral density (BMD)

[AlPater]

Association of the Duration of Ideal Cardiovascular Health Through Adulthood With Cardiometabolic Outcomes and Mortality in the Framingham Offspring Study.
Corlin L, Short MI, Vasan RS, Xanthakis V.
JAMA Cardiol. 2020 Mar 11. doi: 10.1001/jamacardio.2020.0109. [Epub ahead of print]
PMID: 32159731
Abstract
IMPORTANCE:
The American Heart Association ideal cardiovascular health (CVH) score is associated with the risk of cardiovascular disease (CVD) and mortality. However, it is unclear whether the number of years spent in ideal CVH is associated with morbidity or with mortality.
OBJECTIVE:
To evaluate whether living longer with a higher CVH score in midlife is associated with lower risk of hypertension, diabetes, chronic kidney disease, CVD and its subtypes (coronary heart disease, stroke, congestive heart failure, and peripheral artery disease), or all-cause mortality in later life.
DESIGN, SETTING, AND PARTICIPANTS:
This prospective cohort study used data from 1445 participants from 1991 to 2015 who participated in the community-based Framingham Heart Study Offspring investigation conducted in Massachusetts. The CVH scores of participants were assessed at examination cycles 5, 6, and 7 (1991-1995; 1995-1998; and 1998-2001, respectively). Individuals were excluded from analyses of the association between duration of CVH score and outcomes if they had the outcome of interest at the seventh examination. The median follow-up was approximately 16 years. Data were analyzed from April 2018 to October 2019. The CVH score categories were poor for scores 0 to 7, intermediate for scores 8 to 11, and ideal for scores 12 to 14. A composite score was derived based on smoking status, diet, physical activity, resting blood pressure levels, body mass index, fasting blood glucose levels, and total serum cholesterol levels.
MAIN OUTCOMES AND MEASURES:
Number of events and number at risk for each main outcome, including incident hypertension, diabetes, chronic kidney disease, CVD, and all-cause mortality, after the seventh examination.
RESULTS:
Of 1445 eligible participants, the mean (SD) age was 60 (9) years, and 751 (52%) were women. Number of events/number at risk for each main outcome after the seventh examination were 348/795 for incident hypertension, 104/1304 for diabetes, 198/918 for chronic kidney disease, 210/1285 for CVD, and 300/1445 for all-cause mortality. At the seventh examination, participants mostly had poor (568 [39%]) or intermediate (782 [54%]) CVH scores. For each antecedent (before examination cycle 7) 5-year duration that participants had intermediate or ideal CVH, they were less likely to develop adverse outcomes (hazards ratios of 0.67 [95% CI, 0.56-0.80] for incident hypertension, 0.73 [95% CI, 0.57-0.93] for diabetes, 0.75 [95% CI, 0.63-0.89] for chronic kidney disease, 0.73 [95% CI, 0.63-0.85] for CVD, and 0.86 [95% CI, 0.76-0.97] for all-cause mortality) relative to living the same amount of time in poor CVH (referent group). No effect modification was observed by age or by sex.
CONCLUSIONS AND RELEVANCE:
These results suggest that more time spent in better CVH in midlife may have salutary cardiometabolic benefits and may be associated with lower mortality later in life.

Maintenance of liver glycogen during long-term fasting preserves energy state in mice.
López-Soldado I, Bertini A, Adrover A, Duran J, Guinovart JJ.
FEBS Lett. 2020 Mar 11. doi: 10.1002/1873-3468.13770. [Epub ahead of print]
PMID: 32159852
https://sci-hub.tw/https://febs.onlinelibrary.wiley.com/doi/abs/10.1002/1873-3468.13770
Abstract
Glycogen shortage during fasting coincides with dramatic changes in hepatic adenine nucleotide levels. The aim of this work was to study the relevance of liver glycogen in the regulation of the hepatic energy state during food deprivation. To this end, we examined the response of mice with sustained increased liver glycogen content to prolonged fasting. In order to increase hepatic glycogen content, we generated mice that overexpress protein targeting to glycogen (PTG) in the liver (PTGOE  mice). Control and PTGOE  mice were fed ad libitum or fasted for 36 h. Upon fasting, PTGOE  mice retained significant hepatic glycogen stores and maintained hepatic energy status. Furthermore, we show that liver glycogen controls insulin sensitivity, gluconeogenesis, lipid metabolism and ketogenesis upon nutrient deprivation.
KEYWORDS:
AMPK; Energy state; Fasting; Gluconeogenesis; Glycogen; Liver

Differential Impact of Calcium and Vitamin D on Body Composition Changes in Post-Menopausal Women Following a Restricted Energy Diet and Exercise Program.
Kerksick CM, Roberts MD, Campbell BI, Galbreath MM, Taylor LW, Wilborn CD, Lee A, Dove J, Bunn JW, Rasmussen CJ, Kreider RB.
Nutrients. 2020 Mar 7;12(3). pii: E713. doi: 10.3390/nu12030713.
PMID: 32156010
Abstract
Vitamin D and calcium supplementation have been posited to improve body composition and different formulations of calcium may impact bioavailability. However, data are lacking regarding the combinatorial effects of exercise, diet, and calcium and/or vitamin D supplementation on body composition changes in post-menopausal women. Herein, 128 post-menopausal women (51.3 ± 4.5 years, 36.4 ± 5.7 kg/m2, 46.2 ± 4.5% fat) were assigned to diet and supplement groups while participating in a supervised circuit-style resistance-training program (3 d/week) over a 14-week period. Diet groups included: (1) normal diet (CTL), (2) a low-calorie, higher protein diet (LCHP; 1600 kcal/day, 15% carbohydrates, 55% protein, 30% fat), and (3) a low-calorie, higher carbohydrate diet (LCHC; 1600 kcal/day, 55% carbohydrates, 15% protein, 30% fat). Supplement groups consisted of: (1) maltodextrin (PLA), (2) 800 mg/day of calcium carbonate (Ca), and (3) 800 mg/day of calcium citrate and malate and 400 IU/day of vitamin D (Ca+D). Fasting blood samples, body composition, resting energy expenditure, aerobic capacity, muscular strength and endurance measures were assessed. Data were analyzed by mixed factorial ANOVA with repeated measures and presented as mean change from baseline [95% CI]. Exercise training promoted significant improvements in strength, peak aerobic capacity, and blood lipids. Dieting resulted in greater losses of body mass (CTL -0.4 ± 2.4; LCHC -5.1 ± 4.2; LCHP -3.8 ± 4.2 kg) and fat mass (CTL -1.4 ± 1.8; LCHC -3.7 ± 3.7; LCHP -3.4 ± 3.4 kg). When compared to LCHC-PLA, the LCHC + Ca combination led to greater losses in body mass (PLA -4.1 [-6.1, -2.1], Ca -6.4 [-8.1, -4.7], Ca+D -4.4 [-6.4, -2.5] kg). In comparison to LCHC-Ca, the LCHC-Ca+D led to an improved maintenance of fat-free mass (PLA -0.3 [-1.4, 0.7], Ca -1.4 [-2.3, -0.5], Ca+D 0.4 [-0.6, 1.5] kg) and a greater loss of body fat (PLA -2.3 [-3.4, -1.1], Ca -1.3 [-2.3, -0.3], Ca+D -3.6 [-4.8, -2.5]%). Alternatively, no significant differences in weight loss or body composition resulted when adding Ca or Ca+D to the LCHP regimen in comparison to when PLA was added to the LCHP diet. When combined with an energy-restricted, higher carbohydrate diet, adding 800 mg of Ca carbonate stimulated greater body mass loss compared to when a PLA was added. Alternatively, adding Ca+D to the LCHC diet promoted greater% fat changes and attenuation of fat-free mass loss. Our results expand upon current literature regarding the impact of calcium supplementation with dieting and regular exercise. This data highlights that different forms of calcium in combination with an energy restricted, higher carbohydrate diet may trigger changes in body mass or body composition while no impact of calcium supplementation was observed when participants followed an energy restricted, higher protein diet.
KEYWORDS:
dietary supplement; fat loss; training adaptations; weight loss

The Effect of L-Carnitine Supplementation on Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Yarizadh H, Shab-Bidar S, Zamani B, Vanani AN, Baharlooi H, Djafarian K.
J Am Coll Nutr. 2020 Mar 10:1-12. doi: 10.1080/07315724.2019.1661804. [Epub ahead of print]
PMID: 32154768
Abstract
Accumulating evidence of previous experimental studies indicated that L-Carnitine positively ameliorates muscle damage. However, findings from trials vary substantially across studies. Therefore, current meta-analysis aimed to examine the effects of L-Carnitine supplementation on exercise-induced muscle damage. An electronic search of the online literature databases (Medline (PubMed), Scopus and Google Scholar) was performed up to November 2018. Either a fixed-effects model or a random-effects model (Diasorin-Liard) was used in order to estimate the effects size. Cochran's Q test and I2 tests were used to assess the heterogeneity among the studies. Funnel plot and Egger's regression test were also employed in order to assess the publication bias. Of 604 studies, seven eligible randomized controlled trials (RCTs) were included in this meta-analysis. Pooled data from seven studies showed that L-Carnitine resulted in significant improvements in muscle soreness (MS) at the five follow-up time points (0, 24, 48, 72 and 96 hours (h)) compared to placebo. Also, pooled data indicated that L-Carnitine significantly reduced creatine kinase (CK), myoglobin (Mb), and lactate dehydrogenase (LDH) levels at one follow-up period (24 h). However, no effects have been observed beyond this period. Our outcomes indicate that L-Carnitine supplementation improves delayed-onset muscle soreness (DOMS) and markers of muscle damage. Further research is needed to clarify impacts of L-Carnitine on DOMS after different types of mechanical or chemical damages. Key teaching pointsThe effect of L-Carnitine supplementation on exercise-induced muscle damage has come under scrutiny over many years.This systematic review and meta-analyses study investigated the effects of L-Carnitine supplementation on exercise-induced muscle damage.Overall, summary results indicate that L-Carnitine supplementation improves muscle soreness and markers of muscle damage (CK, LDH, and Mb).Overall, L-carnitine supplementation ameliorated muscle damage only in resistance training groups and untrained population.
KEYWORDS:
L-carnitine; Muscle soreness; meta-analysis; muscle damage; supplementation

A prospective study of coffee and tea consumption and the risk of glioma in the UK Biobank.
Creed JH, Smith-Warner SA, Gerke TA, Egan KM.
Eur J Cancer. 2020 Mar 6;129:123-131. doi: 10.1016/j.ejca.2020.01.012. [Epub ahead of print]
PMID: 32151942
Abstract
BACKGROUND:
Coffee and tea have been hypothesised to reduce the risk of some cancers; however, their impact on glioma is less well studied.
METHODS:
We examined associations between self-reported intake of tea and coffee in relation to glioma risk in the UK Biobank. We identified 487 incident glioma cases among 379,259 participants. Hazard ratios (HR) and 95% confidence intervals (CI) for glioma according to caffeinated beverage consumption were calculated using Cox proportional hazards regression with adjustment for age, gender, race and education; daily cups of tea or coffee were included in models considering the other beverage.
RESULTS:
Consuming 4 or more cups of tea was associated with reduced risk of glioma when compared to no tea consumption (HR = 0.69; 95% CI, 0.51-0.94). A significant inverse association was observed for glioblastoma (HR = 0.93 per 1 cup/d increment; 95% CI, 0.89-0.98) and among males for all gliomas combined (HR = 0.95 per 1 cup/d increment; 95% CI, 0.90-1.00). A suggestive inverse association was also observed with greater consumption of coffee (HR = 0.71; 95% CI, 0.49-1.05 for >4 versus 0 cups/d). Results were not materially changed with further adjustment for smoking, alcohol and body mass index. Associations were similar in 2-year and 3-year lagged analyses.
CONCLUSIONS:
In this prospective study, we found a significant inverse association between tea consumption and the risk of developing glioma, and a suggestive inverse association for the consumption of coffee. Further investigation on the possible preventive role of caffeine in glioma is warranted.
KEYWORDS:
Caffeine; Coffee; Cohort; Glioblastoma; Glioma; Tea; UK Biobank

Circulating liver enzymes and risks of chronic diseases and mortality in the prospective EPIC-Heidelberg case-cohort study.
Katzke V, Johnson T, Sookthai D, Hüsing A, Kühn T, Kaaks R.
BMJ Open. 2020 Mar 8;10(3):e033532. doi: 10.1136/bmjopen-2019-033532.
PMID: 32152162
Abstract
OBJECTIVES:
Elevated liver enzyme concentrations in blood are indicative of liver diseases and may provide an early signal for being at risk for other chronic diseases. Our study aimed to assess the relationships of alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate transaminase (AST) and the De Ritis ratio (AST/ALT) with incidence and mortality of cardiovascular diseases (CVD) and the four most common cancers, that is, breast, prostate, colorectal and lung.
SETTING, PARTICIPANTS AND OUTCOME MEASURES:
We analysed a case-cohort sample of the prospective European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort, including cancer (n=1632), cancer mortality (n=761), CVD (n=1070), CVD mortality (n=381) and a random subcohort (n=2739) with an average follow-up duration of 15.6 years. Concentrations of liver enzymes were measured in prediagnostic blood samples and Prentice-weighted Cox regression models were used to estimate HRs with 95% CIs.
RESULTS:
High ALP levels were associated with increased risk for lung cancer and all-cause mortality (highest vs lowest quartile, multivariable adjusted HR=2.39 (95% CI 1.30 to 4.39), HR=1.31 (95% CI 1.02 to 1.67)), high AST levels with all-cause mortality (HR=1.45 (95% CI 1.15 to 1.82)), and a high De Ritis ratio with prostate cancer risk, all-cause and cancer mortality (HR=1.61 (95% CI 1.10 to 2.36), HR=1.60 (95% CI 1.25 to 2.04), HR=1.67 (95% CI 1.26 to 2.23)). Using cut-points for liver enzyme levels above normal, we observed positive associations for all-cause mortality with ALP, GGT and AST, and assigning a combined risk score resulted in positive associations with all-cause and cause-specific mortality.
CONCLUSIONS:
Measurements of serum liver enzymes, as routinely performed in health check-ups, may support the identification of individuals at increased risk for all-cause mortality. Further prospective studies are needed to verify our first results on individual cancers and on a combined risk score.
KEYWORDS:
EPIC; cancer; cardiovascular diseases; case-cohort; liver enzymes

Vegan diet reduces neutrophils, monocytes and platelets related to branched-chain amino acids - A randomized, controlled trial.
Lederer AK, Maul-Pavicic A, Hannibal L, Hettich M, Steinborn C, Gründemann C, Zimmermann-Klemd AM, Müller A, Sehnert B, Salzer U, Klein R, Voll RE, Samstag Y, Huber R.
Clin Nutr. 2020 Feb 24. pii: S0261-5614(20)30059-5. doi: 10.1016/j.clnu.2020.02.011. [Epub ahead of print]
PMID: 32147197
Abstract
BACKGROUND:
Vegan diet (VD) has improved inflammatory activity in patients with rheumatoid arthritis (RA) in several small controlled trials. The underlying mechanism remains widely unclear. We investigated the effect of a VD in comparison to a meat-rich diet (MD) on markers of inflammation (which have been shown to be relevant in patients with RA) in healthy volunteers.
METHODS:
53 healthy, omnivore subjects were randomized to a controlled VD (n = 26) or MD (n = 27) for 4 weeks following a pre-treatment phase of a one week controlled mixed diet. Primary parameters of interest were sialylation of immunoglobulins, percentage of regulatory T-cells and level of interleukin 10 (IL10). Usual care immune parameters used in patients with RA and amino acid serum levels as well as granulocytes and monocytes colony stimulating factor (GM-CSF) serum levels were secondary parameters.
RESULTS:
In the VD group, total leukocyte, neutrophil, monocyte and platelet counts decreased and after four weeks they were significantly lower compared to the MD group (ANCOVA: leukocytes p = 0.003, neutrophils p = 0.001, monocytes p = 0.032, platelets p = 0.004). Leukocytes, neutrophils, monocytes, and platelets correlated with each other and likewise conform with serum levels of branched-chain amino acids, which were significantly lower in the VD compared to the MD group. The primary parameters did not differ between the groups and BMI remained stable in the two groups.
CONCLUSION:
Four weeks of a controlled VD affected the number of neutrophils, monocytes and platelets but not the number or function of lymphocytes. The relation with branched-chain amino acids and GM-CSF suggests a mode of action via the mTOR signaling pathway.
KEYWORDS:
GM-CSF; Granulocytes; Immunoglobulin glycosylation; Inflammation; Leukocytes; Lymphocytes; Nutrition; Rheumatoid arthritis; mTOR

[AlPater]

Drinking frequency modifies an association between salt intake and blood pressure: A cohort study.
Yoshimura R, Yamamoto R, Shinzawa M, Tomi R, Ozaki S, Fujii Y, Ito T, Tanabe K, Moriguchi Y, Isaka Y, Moriyama T.
J Clin Hypertens (Greenwich). 2020 Mar 16. doi: 10.1111/jch.13844. [Epub ahead of print]
PMID: 32175653
Abstract
Salt sensitivity is one of the crucial risk factors of hypertension. The aim of the present prospective cohort study was to assess the clinical impact of alcohol drinking on an association between salt intake and blood pressure. The present study included 451 employees at a pharmaceutical company in Japan who underwent annual health checkups in both 2017 and 2018. The main exposure of interest was self-reported drinking frequency at their first checkups: rarely, occasionally, and daily. To assess the association between the change of salt intake estimated from single-spot urine specimens and that of blood pressure, the differences in systolic/diastolic blood pressure and salt intake between 2017 and 2018 were calculated for each subject. Multivariable-adjusted linear regression models adjusting for clinically relevant factors clarified a drinking frequency-dependent association between Δsalt intake and Δsystolic blood pressure (per 1 g/d of Δsalt intake adjusted β [95% confidence interval] 0.19 [-0.73, 1.12], 0.84 [0.14, 1.53], and 1.78 [0.86, 2.69] in rare, occasional, and daily drinkers). A similar association between Δsalt intake and Δdiastolic blood pressure was also observed (-0.24 [-1.02, 0.54], 0.67 (0.18, 1.16), 0.95 [0.38, 1.51], in rare, occasional, and daily drinkers). The interactions between drinking frequency and Δsalt intake were found to be statistically significant (P for interaction = .028 and .006 for ∆systolic blood pressure and ∆diastolic blood pressure, respectively). The present study identified enhanced salt sensitivity in the subjects who drink at a higher frequency, suggesting that the reduction in alcohol consumption may improve salt sensitivity in higher frequency drinkers.
KEYWORDS:
alcohol drinking; cohort study; salt sensitivity

Effects of eicosapentaenoic acid and docosahexaenoic acid versus α-linolenic acid supplementation on cardiometabolic risk factors: a meta-analysis of randomized controlled trials.
Chen H, Deng G, Zhou Q, Chu X, Su M, Wei Y, Li L, Zhang Z.
Food Funct. 2020 Mar 16. doi: 10.1039/c9fo03052b. [Epub ahead of print] Review.
PMID: 32175534
Abstract
Previous randomized controlled trials (RCTs) made direct comparisons between EPA/DHA versus ALA on improving cardiovascular risk factors and have reached inconsistent findings. The aim of this meta-analysis was to compare the effects of EPA/DHA vs. ALA supplementation on cardiometabolic disturbances. Databases including MEDLINE, Embase, PubMed and Cochrane Trials were searched until December 2019. The pooled effects (weighted mean difference, WMD) of outcomes with moderate and high heterogeneity were calculated with a random-effects model, while low heterogeneity was calculated with a fixed-effect model. Fourteen RCTs with 1137 participants who met the eligibility criteria were pooled. Compared with participants supplemented with ALA, those who received EPA/DHA supplementation experienced a greater reduction in triglycerides (TG) (WMD -0.191 mmol l-1; 95% CI -0.249, -0.133) but a greater increase in high-density lipoprotein (HDL) (WMD 0.033 mmol l-1; 95% CI 0.004, 0.062), low-density lipoprotein (LDL) (WMD 0.130 mmol l-1; 95% CI 0.006, 0.253) and total cholesterol (TC) (WMD 0.179 mmol l-1; 95% CI 0.006, 0.352). In subgroup analyses, the WMD for TG was much lower in trials with participants >40 years old (-0.246 mmol l-1; 95% CI -0.325, -0.167). When DHA and EPA were separately administered, modest increases in HDL were observed in trials that used DHA as a supplement (0.161 mmol l-1; 95% CI 0.017, 0.304), but not in trials using EPA (0.040 mmol l-1; 95% CI -0.132, 0.212). In conclusion, dietary EPA/DHA supplementation improved the TG and HDL status but increased LDL levels in comparison with ALA.

VLDL/LDL serves as the primary source of cholesterol in the adrenal glucocorticoid response to food deprivation.
van der Sluis RJ, Depuydt MAC, Van Eck M, Hoekstra M.
Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Mar 10:158682. doi: 10.1016/j.bbalip.2020.158682. [Epub ahead of print]
PMID: 32169652
Abstract
The contribution of individual lipoprotein species to the generation of the adrenal cholesterol pool used for the synthesis of anti-inflammatory glucocorticoid species remains unknown. Here we examined the impact of specific lowering of very low-density lipoprotein (VLDL) and low-density (LDL) levels on adrenal cholesterol and glucocorticoid homeostasis. Hereto, lethally-irradiated hypercholesterolemic apolipoprotein E (APOE) knockout mice received APOE-containing bone marrow from wild-type mice (n = 6) or APOE knockout control bone marrow (n = 10) and were subsequently fed a regular chow diet. Transplantation with wild-type bone marrow was associated with a 10-fold decrease in VLDL/LDL-cholesterol levels. No changes were observed in adrenal weights, adrenal cholesterol content, or basal plasma corticosterone levels. However, food deprivation-induced corticosterone secretion was 64% lower (P < 0.05) in wild-type bone marrow recipients as compared to APOE knockout bone marrow recipients, in the context of similar plasma adrenocorticotropic hormone (ACTH) levels. A parallel 19-29% decrease in adrenal relative mRNA expression levels of ACTH-responsive genes SR-BI (P < 0.01), STAR (P < 0.05), and CYP11A1 (P < 0.05) was detected. In support of relative glucocorticoid insufficiency, blood lymphocyte and eosinophil concentrations were respectively 2.4-fold (P < 0.01) and 8-fold (P < 0.001) higher in wild-type bone marrow recipients under food deprivation stress conditions. In conclusion, we have shown that a selective lowering of VLDL/LDL levels in APOE knockout mice through a transplantation with APOE-containing wild-type bone marrow is associated with a decreased maximal adrenal glucocorticoid output. Our studies provide experimental support for the hypothesis that, in vivo, VLDL/LDL serves as the primary source of cholesterol used for glucocorticoid synthesis during food deprivation stress.
KEYWORDS:
Adrenal; Apolipoprotein E; Bone marrow transplantation; Cholesterol; Glucocorticoid; Lipoprotein

Accelerometer-measured physical activity and sedentary time in a cohort of US adults followed for up to 13 years: the influence of removing early follow-up on associations with mortality.
Tarp J, Hansen BH, Fagerland MW, Steene-Johannessen J, Anderssen SA, Ekelund U.
Int J Behav Nutr Phys Act. 2020 Mar 14;17(1):39. doi: 10.1186/s12966-020-00945-4.
PMID: 32169059
Abstract
BACKGROUND:
Observational studies linking physical activity with mortality are susceptible to reverse causation bias from undiagnosed and prevalent diseases. Researchers often attempt to deal with reverse causation bias by excluding deaths occurring within the first 1 or 2 years from the analysis, but it is unclear if excluding deaths within this time-frame is sufficient to remove bias.
METHODS:
We examined associations between total and intensity-specific physical activity and sedentary time with all-cause mortality in a prospective cohort of 3542 individuals from the 2003-2006 NHANES cycles. In order to yield measures of association hypothesized as minimally influenced by reverse causation bias the primary analysis excluded individuals with < 5 years of follow-up. Accelerometer-measured physical activity was linked with recently updated vital status from the National Death Index with a median follow-up of 10.8 years.
RESULTS:
Hazard ratios (95% confidence intervals) were 0.74 (0.53, 1.04), 0.52 (0.37, 0.73), and 0.61 (0.38, 1.01) for ascending quartiles of total physical activity against the least active reference. Hazard ratios for ascending moderate-to-vigorous physical activity quartiles against the reference were 0.67 (0.47, 1.96), 0.67 (0.47, 0.95), and 0.68 (0.39, 1.18). Associations for light intensity physical activity and sedentary time were smaller in magnitude and all confidence intervals included unity. Total activity and moderate-to-vigorous physical activity hazard ratios from analyses only excluding deaths within the first 2 years were inflated by 13 and 26% relative to analysis restricted to ≥5 years of follow-up.
CONCLUSIONS:
The pattern of associations suggested total physical activity and moderate-to-vigorous physical activity were associated with lower mortality after more than 10 years of follow-up and excluding the first 5 years of observation time to minimize the impact of reverse causation bias. Excluding deaths within the first 2 years appeared insufficient to minimize the impact of reserve causation bias.
KEYWORDS:
Cohort study; Epidemiology; Exercise; Leisure activity

Dietary advanced glycation end-products (AGEs) and risk of breast cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO).
Omofuma OO, Turner DP, Peterson LL, Merchant AT, Zhang J, Steck SE.
Cancer Prev Res (Phila). 2020 Mar 13. pii: canprevres.0457.2019. doi: 10.1158/1940-6207.CAPR-19-0457. [Epub ahead of print]
PMID: 3216988
Abstract
Advanced glycation end-products (AGEs) are implicated in the pathogenesis of several chronic diseases including cancer. AGEs are produced endogenously but can also be consumed from foods. AGE formation in food is accelerated during cooking at high temperatures. Certain high fat or highly processed foods have high AGE values. The objective of the study was to assign and quantify NƐ-carboxymethyl-lysine (CML)-AGE content in food and investigate the association between dietary AGE intake and breast cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). The study included women enrolled in the intervention arm who were cancer-free at baseline and completed a baseline questionnaire and food frequency questionnaire (DQX). CML-AGE values were assigned and quantified to foods in the DQX using a published AGE database. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs of breast cancer among all women, and stratified by race/ethnicity, invasiveness of disease, and hormone receptor status. After a median 11.5 years of follow-up, 1,592 women were diagnosed with breast cancer. Higher CML-AGE intake was associated with increased risk of breast cancer among all women (HRQ5 VS Q1:1.30, 95% CI: 1.04-1.62; P-trend: 0.04) and in non-Hispanic white women (HRT3 VS T1: 1.21, 95% CI: 1.02-1.44). Increased CML-AGE intake was associated with increased risk of in situ (HRT3 VS T1: 1.49, 95% CI: 1.11-2.01) and hormone receptor positive (HRT3 VS T1: 1.24, 95% CI: 1.01-1.53) breast cancers. In conclusion, high intake of dietary AGE may contribute to increased breast cancer.

Soy food intake and pancreatic cancer risk: The Japan Public Health Center-based Prospective Study.
Yamagiwa Y, Sawada N, Shimazu T, Yamaji T, Goto A, Takachi R, Ishihara J, Iwasaki M, Inoue M, Tsugane S.
Cancer Epidemiol Biomarkers Prev. 2020 Mar 13. pii: cebp.1254.2019. doi: 10.1158/1055-9965.EPI-19-1254. [Epub ahead of print]
PMID: 32169996
Abstract
BACKGROUND:
Although the poor prognosis and increasing incidence of pancreatic cancer highlight the need for prevention strategies, few lifestyle risk factors for pancreatic cancer have yet been identified. Soybeans contain various bioactive compounds. However, the association between soy food intake and pancreatic cancer risk remains unknown.
METHODS:
The Japan Public Health Center-based Prospective Study (JPHC Study) is a cohort study conducted in a general Japanese population. To determine the association of soy food intake and pancreatic cancer incidence, we analyzed 90,185 participants who responded to a questionnaire on medical history and lifestyle factors, including dietary factors based on a food-frequency questionnaire in 1995-1998, using Cox proportional hazards models.
RESULTS:
During a median follow-up of 16.9 years, 577 cases of pancreatic cancer were identified. In the multivariate-adjusted model, total soy food intake was statistically significantly associated with an increased risk of pancreatic cancer (hazard ratio {HR} for the highest versus lowest intake quartile: 1.48; 95% confidence interval [CI]: 1.15-1.92; P-trend = 0.007). Among soy foods, non-fermented soy food intake showed a statistically significant positive association with pancreatic cancer (HR: 1.41; 95% CI: 1.09-1.81; P-trend = 0.008), whereas fermented soy food intake showed no association (HR: 0.96; 95% CI: 0.73-1.26; P-trend = 0.982).
CONCLUSIONS:
Higher intake of soy foods, particularly non-fermented soy foods, might increase pancreatic cancer risk.
IMPACT:
This study is the first to report an association between the intake of various soy foods and pancreatic cancer risk. Further studies are required to confirm our findings.

Associations of egg consumption with incident cardiovascular disease and all-cause mortality.
Xia X, Liu F, Yang X, Li J, Chen J, Liu X, Cao J, Shen C, Yu L, Zhao Y, Wu X, Zhao L, Li Y, Huang J, Lu X, Gu D.
Sci China Life Sci. 2020 Mar 10. doi: 10.1007/s11427-020-1656-8. [Epub ahead of print]
PMID: 32170624
Abstract
Eggs are nutrient-dense while also loaded with abundant cholesterol, thus making the public hesitant about their consumption. We conducted the study to investigate if egg consumption is associated with incident cardiovascular disease (CVD) and all-cause mortality. Using the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China, we included 102,136 adults free of CVD and assessed their egg consumption with food-frequency questionnaires. CVD endpoints and all-cause mortality were confirmed during follow-ups by interviewing participants or their proxies and checking hospital records/death certificates. The HRs (95% CIs) were calculated using the cohort-stratified Cox regression models. During 777,163 person-years of follow-up, we identified 4,848 incident CVD and 5,511 deaths. U-shaped associations of egg consumption with incident CVD and all-cause mortality were observed. Compared with consumption of 3-<6/week, the multivariable-adjusted HRs (95% CIs) of <1/week and ≥10/week for incident CVD were 1.22 (1.11 to 1.35) and 1.39 (1.28 to 1.52), respectively. The corresponding HRs (95% CIs) for all-cause mortality were 1.29 (1.18 to 1.41) and 1.13 (1.04 to 1.24). Our findings identified that both low and high consumption were associated with increased risk of incident CVD and all-cause mortality, highlighting that moderate egg consumption of 3-<6/week should be recommended for CVD prevention in China.
KEYWORDS:
all-cause mortality; cardiovascular disease; cohort study; egg consumption

Edited March 17, 2020 by AlPater

[AlPater]

Dietary intake of choline and phosphatidylcholine and risk of type 2 diabetes in men: The Kuopio Ischaemic Heart Disease Risk Factor Study.
Virtanen JK, Tuomainen TP, Voutilainen S.
Eur J Nutr. 2020 Mar 20. doi: 10.1007/s00394-020-02223-2. [Epub ahead of print]
PMID: 32198672
Abstract
PURPOSE:
To investigate associations of total dietary choline intake and its major dietary form, phosphatidylcholine, with type 2 diabetes risk.
METHODS:
We included 2332 men aged 42-60 years at baseline in 1984-1989 from the Kuopio Ischaemic Heart Disease Risk Factor Study in eastern Finland. Dietary intakes were assessed with 4-d food recording at baseline. Type 2 diabetes diagnosis was based on self-administered questionnaires, fasting and 2-h oral glucose tolerance test blood glucose measurements, or by record linkage to national health registries. Multivariable-adjusted Cox proportional hazards regression models were used for statistical analysis.
RESULTS:
During the mean 19.3-year follow-up, 432 men had type 2 diabetes diagnosis. After multivariable adjustments, those in the highest vs. lowest choline intake quartile had 25% (95% CI 2-43%) lower relative risk (P trend across quartiles = 0.02) and those in the highest vs. lowest phosphatidylcholine quartile had 41% (95% CI 22-55%) lower relative risk (P trend < 0.001) of type 2 diabetes.
CONCLUSIONS:
Higher choline intake, especially phosphatidylcholine, was associated with lower type 2 diabetes risk among men.
KEYWORDS:
Choline; Diet; Phosphatidylcholine; Population study; Prospective study; Type 2 diabetes

Association of magnesium intake with type 2 diabetes and total stroke: an updated systematic review and meta-analysis.
Zhao B, Zeng L, Zhao J, Wu Q, Dong Y, Zou F, Gan L, Wei Y, Zhang W.
BMJ Open. 2020 Mar 19;10(3):e032240. doi: 10.1136/bmjopen-2019-032240.
PMID: 32198298
Abstract
OBJECTIVE:
The detailed associations between type 2 diabetes (T2D) and total stroke and magnesium intake as well as the dose-response trend should be updated in a timely manner.
DESIGN:
Systematic review and meta-analyses.
DATA SOURCES:
PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov were rigorously searched from inception to 15 March 2019.
ELIGIBILITY CRITERIA:
Prospective cohort studies investigating these two diseases were included.
DATA SYNTHESIS:
Relative risk (RR) and 95% CI in random effects models as well as absolute risk (AR) were pooled to calculate the risk of T2D and stroke. Methodological quality was assessed by the Newcastle-Ottawa Scale.
RESULTS:
Forty-one studies involving 53 cohorts were included. The magnitude of the risk was significantly reduced by 22% for T2D (RR 0.78 (95% CI 0.75 to 0.81); p<0.001; AR reduction 0.120%), 11% for total stroke (RR 0.89 (95% CI 0.83 to 0.94); p<0.001; AR reduction 0.281%) and 12% for ischaemic stroke (RR 0.88 (95% CI 0.81 to 0.95); p=0.001; AR reduction 0.246%) when comparing the highest magnesium intake to the lowest. The inverse association still existed when studies on T2D were adjusted for cereal fibre (RR 0.79; p<0.001) and those on total stroke were adjusted for calcium (RR 0.89; p=0.040). Subgroup analyses suggested that the risk for total and ischaemic stroke was significantly decreased in females, participants with ≥25 mg/m2 body mass index and those with ≥12-year follow-up; the reduced risk in Asians was not as notable as that in North American and European populations.
CONCLUSIONS:
Magnesium intake has significantly inverse associations with T2D and total stroke in a dose-dependent manner. Feasible magnesium-rich dietary patterns may be highly beneficial for specific populations and could be highlighted in the primary T2D and total stroke prevention strategies disseminated to the public.
KEYWORDS:
magnesium intake; meta-analysis; stroke; type 2 diabetes

Casein- and pea-enriched high-protein diet can take care of the reprotoxic effects of arsenic in male rats.
Biswas S, Kumar Mukhopadhyay P.
Andrologia. 2020 Mar 20:e13560. doi: 10.1111/and.13560. [Epub ahead of print]
PMID: 32196711
Abstract
Arsenic toxicity is a significant health problem featured with several incidents of male reproductive dysfunctions. We studied the protective effects of a casein- and pea-enriched formulated high-protein diet (FHPD) on arsenic-mediated testicular dysfunctions in rats. Adult male rats sustained on either a benchmark diet (n = 8 or an isocaloric FHPD (n = 8 were gavaged with arsenic trioxide (3mg/kg body wt/rat/day) for 30 consecutive days. A vehicle-fed group (n = 8 maintained on the standard diet served as control. The arsenic-treated group continued on the standard diet had a significantly reduced testicular and accessory sex organs weights. They exhibited decreased count, motility, viability and disrupted plasma membrane integrity of caudal spermatozoa with a higher incidence of gross morphological anomalies and DNA damage. Attenuated steroidogenic enzyme activities and low serum testosterone level vouched for a compromised state of testicular steroidogenesis. An increased testicular malondialdehyde and protein carbonyl contents coupled with impaired activities of antioxidant enzymes and free radical scavengers mirrored a situation of exacerbated testicular oxidative imbalance and disrupted redox homeostasis. FHPD, by and large, countermanded testicular steroidogenesis and antioxidant defence system and revoked the ill effects of arsenic. We conclude that specific protein-enriched diet may serve as prospective weaponry in encountering the arsenic-threatened testicular functions.
KEYWORDS:
Arsenic; DNA damage; casein and pea; spermatozoa; ultrastructure

Sex-specific metabolic responses to 6 hours fasting during the active phase in young mice.
Freire T, Senior AM, Perks R, Pulpitel T, Clark X, Brandon AE, Wahl D, Hatchwell L, Le Couteur DG, Cooney G, Larance M, Simpson SJ, Solon-Biet SM.
J Physiol. 2020 Mar 21. doi: 10.1113/JP278806. [Epub ahead of print]
PMID: 32198893
Abstract
KEY POINTS:
Night time/active phase food restriction for 6 hr impaired glucose intolerance in young male and female mice. Females displayed increased capacity for lipogenesis and triglyceride storage in response to a short daily fast. Females had lower fasting insulin levels and an increased potential for utilizing fat for energy through β-oxidation compared to males. The need for the inclusion of both sexes, and the treatment of sex as an independent variable, is emphasized within the context of this fasting regime.
ABSTRACT:
There is growing interest in understanding the mechanistic significance and benefits of fasting physiology in combating obesity. Increasing the fasting phase of a normal day can promote restoration and repair mechanisms that occur during the post-absorptive period. Most studies exploring the effect of restricting food access on mitigating obesity have done so with a large bias towards the use of male mice. Here, we disentangle the roles of sex, food intake and food withdrawal in the response to a short-term daily fasting intervention, where food was removed for six hours in the dark/active phase of young, 8-week old mice. We showed that the removal of food during the dark phase impaired glucose tolerance in males and females, possibly due to the circadian disruption induced by this feeding protocol. Although both sexes demonstrated similar patterns of food intake, body composition and various metabolic markers, there were clear sex differences in the magnitude and extent of these responses. While females displayed enhanced capacity for lipogenesis and triglyceride storage, they also had low fasting insulin levels and an increased potential for utilizing available energy sources such as fat for energy through β-oxidation. Our results highlight the intrinsic biological and metabolic disparities between male and female mice, emphasizing the growing need for the inclusion of both sexes in scientific research. Furthermore, our results illustrate sex-specific metabolic pathways that regulate lipogenesis, obesity and overall metabolic health. This article is protected by copyright. All rights reserved.
KEYWORDS:
circadian rhythm; food timing; lipogenesis; obesity; sex effects; short daily fasting

Relationship Between Dietary Magnesium Intake and Incident Heart Failure Among Older Women: The WHI.
Wu WC, Huang M, Taveira TH, Roberts MB, Martin LW, Wellenius GA, Johnson KC, Manson JE, Liu S, Eaton CB.
J Am Heart Assoc. 2020 Apr 7;9(7):e013570. doi: 10.1161/JAHA.119.013570. Epub 2020 Mar 20.
PMID: 32192409
Abstract
Background Women represent a large proportion of the growing heart failure (HF) epidemic, yet data are lacking regarding optimal dietary and lifestyle prevention strategies for them. Specifically, the association between magnesium intake and HF in a multiracial cohort of women is uncertain. Methods and Results We included 97 725 postmenopausal women from the WHI (Women's Health Initiative) observational studies and placebo arms of the hormone trial. Magnesium intake was measured at baseline by a 122-item validated food-frequency questionnaire and stratified into quartiles based on diet only, total intake (diet with supplements), and residual intake (calibration by total energy). Incident hospitalized HF (2153 events, median follow-up 8.1 years) was adjudicated by medical record abstraction. In Cox proportional hazards models, we evaluated the association between magnesium intake and HF adjusting for potential confounders. Analyses were repeated on a subcohort (n=18 745; median-follow-up, 13.2 years) for whom HF cases were subclassified into preserved ejection fraction (526 events), reduced ejection fraction (291 events) or unknown (168 events). Most women were white (85%) with a mean age of 63. Compared with the highest quartile of magnesium intake, women in the lowest quartile had an increased risk of incident HF, with adjusted hazard ratios of 1.32 (95% CI, 1.02-1.71) for diet only (P trend=0.03), 1.26 (95% CI, 1.03-1.56) for total intake, and 1.31 (95% CI, 1.02-1.67) for residual intake. Results did not significantly vary by race. Subcohort analyses showed low residual magnesium intake was associated with HF with reduced ejection fraction (hazard ratio, 1.81, lowest versus highest quartile; 95% CI, 1.08-3.05) but not HF with preserved ejection fraction. Conclusions Low magnesium intake in a multiracial cohort of postmenopausal women was associated with a higher risk of incident HF, especially HF with reduced ejection fraction.
KEYWORDS:
heart failure with preserved ejection fraction; heart failure with reduced ejection fraction; residual method; total magnesium

Potato consumption is associated with total and cause-specific mortality: a population-based cohort study and pooling of prospective studies with 98,569 participants.
Mazidi M, Katsiki N, Mikhailidis DP, Pella D, Banach M.
Arch Med Sci. 2020 Feb 11;16(2):260-272. doi: 10.5114/aoms.2020.92890. eCollection 2020.
PMID: 32190135
Abstract
INTRODUCTION:
The long-term effect of potato consumption on mortality and cardiovascular (CV) and cardiometabolic risk factors is still largely unknown. Using the National Health and Nutrition Examination Surveys (NHANES) 1999-2010, we evaluted the long-term impact of potato intake on total and cause-specific (cardiovascular disease (CVD), cerebrovascular disease and cancer) mortality, and the results were next validated in a systematic review and meta-analysis of cohort studies investigating pooled associations of potato consumption with all-cause and cause-specific death.
MATERIAL AND METHODS:
Vital status up to December 31, 2011 was ascertained in NHANES. Cox proportional hazards were applied to determine the hazard ratios (HRs) and 95% confidence intervals (95% CI) of mortality for each quartile of the potato intake, with the lowest quartile (Q1 - with the lowest intake) used as a reference. In the meta-analysis we used adjusted Cox regression to determine the risk ratio (RR) and 95% CI, as well as random effects models and generic inverse variance methods to synthesize quantitative and pooled data, followed by a leave-one-out method for sensitivity analysis.
RESULTS:
Among 24,856 participants included, 3433 deaths occurred during the mean follow-up of 6.4 years. In multivariate adjusted models, total (42%), CVD (65%), cerebrovascular (26%) and cancer (52%) mortality risk was greater in individuals with higher potato consumption than those with the lowest intake (p < 0.001 for all comparisons). However, this link disappeared after adjustment for confounding factors. Results from pooling current prospective studies revealed a non-significant association between total (RR = 1.25, 0.98-1.60, p = 0.066), CVD (RR = 0.99, 0.90-1.08, p = 0.845) and stroke mortality (RR = 0.94, 0.85-1.03, p = 0.214) with potato consumption. Individuals with a higher potato intake had a less favorable profile of cardiometabolic factors, including greater waist circumference (97.2 vs. 99.5 cm, p < 0.001) and a less favorable profile of systolic and diastolic blood pressure, levels of triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C) and TG/HDL-C ratio (p < 0.001 for all comparisons).
CONCLUSIONS:
Our results revealed no significant effects of potato intake on long-term mortality rates, whereas higher potato consumption was adversely related to cardiometabolic risk factors. These findings should be taken into consideration for public health strategies, establishing the position for potatoes in the food pyramid.
KEYWORDS:
cardiometabolic; cardiovascular disease; meta-analysis; mortality; potato; stroke

Hepatic de novo lipogenesis is suppressed and fat oxidation is increased by omega-3 fatty acids at the expense of glucose metabolism.
Green CJ, Pramfalk C, Charlton CA, Gunn PJ, Cornfield T, Pavlides M, Karpe F, Hodson L.
BMJ Open Diabetes Res Care. 2020 Mar;8(1). pii: e000871. doi: 10.1136/bmjdrc-2019-000871.
PMID: 32188593 Free Article
Abstract
OBJECTIVE:
Increased hepatic de novo lipogenesis (DNL) is suggested to be an underlying cause in the development of nonalcoholic fatty liver disease and/or insulin resistance. It is suggested that omega-3 fatty acids (FA) lower hepatic DNL. We investigated the effects of omega-3 FA supplementation on hepatic DNL and FA oxidation using a combination of human in vivo and in vitro studies.
RESEARCH DESIGN AND METHODS:
Thirty-eight healthy men were randomized to take either an omega-3 supplement (4 g/day eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) as ethyl esters) or placebo (4 g/day olive oil) and fasting measurements were made at baseline and 8 weeks. The metabolic effects of omega-3 FAs on intrahepatocellular triacylglycerol (IHTAG) content, hepatic DNL and FA oxidation were investigated using metabolic substrates labeled with stable-isotope tracers. In vitro studies, using a human liver cell-line was undertaken to gain insight into the intrahepatocellular effects of omega-3 FAs.
RESULTS:
Fasting plasma TAG concentrations significantly decreased in the omega-3 group and remained unchanged in the placebo group. Eight weeks of omega-3 supplementation significantly decreased IHTAG, fasting and postprandial hepatic DNL while significantly increasing dietary FA oxidation and fasting and postprandial plasma glucose concentrations. In vitro studies supported the in vivo findings of omega-3 FAs (EPA+DHA) decreasing intracellular TAG through a shift in cellular metabolism away from FA esterification toward oxidation.
CONCLUSIONS:
Omega-3 supplementation had a potent effect on decreasing hepatic DNL and increasing FA oxidation and plasma glucose concentrations. Attenuation of hepatic DNL may be considered advantageous; however, consideration is required as to what the potential excess of nonlipid substrates (eg, glucose) will have on intrahepatic and extrahepatic metabolic pathways.
KEYWORDS:
de novo lipogenesis; fatty acid oxidation; liver fat; omega-3 fatty acids

Associations of fat and carbohydrate intake with cardiovascular disease and mortality: prospective cohort study of UK Biobank participants.
Ho FK, Gray SR, Welsh P, Petermann-Rocha F, Foster H, Waddell H, Anderson J, Lyall D, Sattar N, Gill JMR, Mathers JC, Pell JP, Celis-Morales C.
BMJ. 2020 Mar 18;368:m688. doi: 10.1136/bmj.m688.
PMID: 32188587 Free Article
https://www.bmj.com/content/bmj/368/bmj.m688.full.pdf
Abstract
OBJECTIVE:
To investigate the association of macronutrient intake with all cause mortality and cardiovascular disease (CVD), and the implications for dietary advice.
DESIGN:
Prospective population based study.
SETTING:
UK Biobank.
PARTICIPANTS:
195 658 of the 502 536 participants in UK Biobank completed at least one dietary questionnaire and were included in the analyses. Diet was assessed using Oxford WebQ, a web based 24 hour recall questionnaire, and nutrient intakes were estimated using standard methodology. Cox proportional models with penalised cubic splines were used to study non-linear associations.
MAIN OUTCOME MEASURES:
All cause mortality and incidence of CVD.
RESULTS:
4780 (2.4%) participants died over a mean 10.6 (range 9.4-13.9) years of follow-up, and 948 (0.5%) and 9776 (5.0%) experienced fatal and non-fatal CVD events, respectively, over a mean 9.7 (range 8.5-13.0) years of follow-up. Non-linear associations were found for many macronutrients. Carbohydrate intake showed a non-linear association with mortality; no association at 20-50% of total energy intake but a positive association at 50-70% of energy intake (3.14 v 2.75 per 1000 person years, average hazard ratio 1.14, 95% confidence interval 1.03 to 1.28 (60-70% v 50% of energy)). A similar pattern was observed for sugar but not for starch or fibre. A higher intake of monounsaturated fat (2.94 v 3.50 per 1000 person years, average hazard ratio 0.58, 0.51 to 0.66 (20-25% v 5% of energy)) and lower intake of polyunsaturated fat (2.66 v 3.04 per 1000 person years, 0.78, 0.75 to 0.81 (5-7% v 12% of energy)) and saturated fat (2.66 v 3.59 per 1000 person years, 0.67, 0.62 to 0.73 (5-10% v 20% of energy)) were associated with a lower risk of mortality. A dietary risk matrix was developed to illustrate how dietary advice can be given based on current intake.
CONCLUSION:
Many associations between macronutrient intake and health outcomes are non-linear. Thus dietary advice could be tailored to current intake. Dietary guidelines on macronutrients (eg, carbohydrate) should also take account of differential associations of its components (eg, sugar and starch).

Significant reduction in the LDL cholesterol increases the risk of intracerebral hemorrhage: a systematic review and meta-analysis of 33 randomized controlled trials.
Cheng Y, Qiao L, Jiang Z, Dong X, Feng H, Gui Q, Lu Y, Liang Y.
Am J Transl Res. 2020 Feb 15;12(2):463-477. eCollection 2020.
PMID: 32194896
Abstract
The dose-dependent pleiotropic effects of statin therapy may have unwanted side effects such as increasing the risk of intracerebral hemorrhage (ICH). The relationships among statin therapy, LDL-cholesterol levels, and ICH risk remain controversial. Here, we conduct a systematic review and meta-analysis of dose-dependent statin therapy and ICH risk. Eligible articles were identified by searching MEDLINE from inception up to December 1, 2018. Reference lists of previous meta-analyses were manually searched to retrieve all relevant publications. Statin doses were allocated into one of two groups according to the observed reduction of LDL cholesterol: doses that lowered LDL-cholesterol levels ≥35% were regarded as high-dose statin therapy, whereas those that lowered LDL-cholesterol levels <35% were regarded as low-dose statin therapy. We retrieved 33 studies involving 203,305 subjects. The pooled analysis indicated that high-dose statin treatment significantly increased the risk of ICH [relative risk (RR), 1.35; 95% confidence interval (CI), 1.08-1.68] and reduced the risk of all stroke (RR, 0.85; 95% CI, 0.78-0.92), ischemic stroke (RR, 0.79; 95% CI, 0.72-0.87), and all-cause mortality (RR, 0.94; 95% CI, 0.90-0.98). The analyses did not detect any association between low-dose statin treatment and ICH (RR, 1.05; 95% CI, 0.88-1.25). Low-dose statin therapy significantly reduced the incidence of all stroke (RR, 0.84; 95% CI, 0.79-0.89), ischemic stroke (RR, 0.81; 95% CI, 0.76-0.86), and all-cause mortality (RR, 0.94; 95% CI, 0.92-0.97). Our data indicate that low-dose statin therapy is a safe and effective ICH treatment, whereas high-dose statin therapy is associated with increased ICH risk. Hence, our meta-analysis suggests that the dose-dependent pleiotropic effects of statin therapy are related to the measured reduction in LDL cholesterol.
KEYWORDS:
High-dose statin therapy; intracerebral hemorrhage; low-dose statin therapy; meta-analysis

Effects of dairy products on bone mineral density in healthy postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.
Shi Y, Zhan Y, Chen Y, Jiang Y.
Arch Osteoporos. 2020 Mar 18;15(1):48. doi: 10.1007/s11657-020-0694-y. Review.
PMID: 32185512
Abstract
PURPOSE:
To investigate the effects of dairy products on bone mineral density (BMD) in healthy postmenopausal women.
METHODS:
The EMBASE, Cochrane Library, Medline, and Web of Science databases were systematically searched for relevant studies. The pooled standardized mean difference (SMD) with its 95% confidence interval (CI) was used as the effect size. Subgroup analysis and Begg's test were conducted.
RESULTS:
Six studies with a total of 618 participants were included in the meta-analysis. Milk was the main dairy product used in the trials. There was a significant association between dairy product consumption and BMD of the lumbar spine (SMD 0.21, 95% CI 0.05-0.37, P = 0.009), femoral neck (SMD 0.36, 95% CI 0.19-0.53, P < 0.001), total hip (SMD 0.37, 95% CI 0.20-0.55, P < 0.001), and total body (SMD 0.58, 95% CI 0.39-0.77, P < 0.001). Subgroup analysis suggested that there was a positive effect of dairy product consumption on the BMD of the total hip starting from 12 months and the femoral neck starting from 18 months. There was also a positive association with the BMD in the four sites in people living in low-calcium intake countries.
CONCLUSION:
This meta-analysis provides evidence that dairy products can increase BMD in healthy postmenopausal women. Dairy product consumption should be considered an effective public health measure to prevent osteoporosis in postmenopausal women.
KEYWORDS:
Bone mineral density; Dairy products; Osteoporosis; Postmenopausal women

Beneficial impact of exercise on bone mass in individuals under calorie restriction: a systematic review and Meta-analysis of randomized clinical trials.
Yarizadeh H, Asadi S, Baharlooi H, Setayesh L, Kakavandi NR, Hambly C, Djafarian K, Mirzaei K.
Crit Rev Food Sci Nutr. 2020 Mar 17:1-13. doi: 10.1080/10408398.2020.1739620. [Epub ahead of print]
PMID: 32180431
https://sci-hub.tw/10.1080/10408398.2020.1739620
Abstract
Background: A major therapeutic goal in weight management should be total body fat reduction whereas as preserving lean body mass and bone mass density. It is uncertain if an exercise program reduces the adverse effects of calorie restriction-induced weight loss in adults.Objective: The aim of the present study was to evaluate the differences in bone mass between adults who enrolled in a calorie restriction or an exercise-calorie restriction induced weight loss program.Data sources: Both PubMed and Scopus libraries were searched up to February 2020.Methods: Systematic reviews and a meta-analysis were carried out of randomized clinical trials (published to February 2020) on differences in bone mineral density and content (BMD and BMC) of adults who lost weight by calorie restriction alone (CR) or exercise-calorie restriction (CR-E). The study quality was calculated using the Cochrane scoring system. Retrieved data were pooled when weight mean differences (WMDs) were computed between two groups for BMD and BMC at various sites of the body.Results: Thirteen studies, with a total of 852 participants were included. Available evidence found significantly higher BMD at the hip (WMD: 0.03 g/cm2, 95%CI: 0.01 to 0.04, p < 0.001) and femoral neck WMD: 0.03 g/cm2, 95%CI: 0.01 to 0.05, p < 0.001) and total body BMC (WMD: 0.13 kg/cm2, 95%CI: -0.10 to 0.36, p < 0.001) in the CR-E compared to the CR weight loss group. In contrast, all changes in total body BMD (WMD: 0.00 g/cm2, 95%CI: -0.01 to 0.02, p = 0.57) and lumbar spine BMD (WMD: 0.00 g/cm2, 95%CI: -0.01 to 0.01, p = 0.89) were not statistically significant.Limitations: Little evidence was available for different sexes separately. Most individuals were postmenopausal females and no subgroup analysis could be conducted based on menopausal status.Conclusion: This study suggests that physical training can preserve and even significantly increase the bone mass of the hip and femoral neck during weight reduction. Of note, various exercise modalities affected BMD at different sites. Similar results were not found for lumbar spine and total body BMD.
KEYWORDS:
Exercise; bone; calorie restriction; meta-analysis

Time-of-Day-Dependent Physiological Responses to Meal and Exercise.
Aoyama S, Shibata S.
Front Nutr. 2020 Feb 28;7:18. doi: 10.3389/fnut.2020.00018. eCollection 2020. Review.
PMID: 32181258
Abstract
The mammalian circadian clock drives the temporal coordination in cellular homeostasis and it leads the day-night fluctuation of physiological functions, such as sleep/wake cycle, hormonal secretion, and body temperature. The mammalian circadian clock system in the body is classified hierarchically into two classes, the central clock in the suprachiasmatic nucleus (SCN) of the hypothalamus and the peripheral clocks in peripheral tissues such as the intestine and liver, as well as other brain areas outside the SCN. The circadian rhythm of various tissue-specific functions is mainly controlled by each peripheral clock and partially by the central clock as well. The digestive, absorptive, and metabolic capacities of nutrients also show the day-night variations in several peripheral tissues such as small intestine and liver. It is therefore indicated that the bioavailability or metabolic capacity of nutrients depends on the time of day. In fact, the postprandial response of blood triacylglycerol to a specific diet and glucose tolerance exhibit clear time-of-day effects. Meal frequency and distribution within a day are highly related to metabolic functions, and optimal time-restricted feeding has the potential to prevent several metabolic dysfunctions. In this review, we summarize the time-of-day-dependent postprandial response of macronutrients to each meal and the involvement of circadian clock system in the time-of-day effect. Furthermore, the chronic beneficial and adverse effects of meal time and eating pattern on metabolism and its related diseases are discussed. Finally, we discuss the timing-dependent effects of exercise on the day-night variation of exercise performance and therapeutic potential of time-controlled-exercise for promoting general health.

Edited March 22, 2020 by AlPater

[AlPater]

Association of Daily Step Count and Step Intensity With Mortality Among US Adults.
Saint-Maurice PF, Troiano RP, Bassett DR Jr, Graubard BI, Carlson SA, Shiroma EJ, Fulton JE, Matthews CE.
JAMA. 2020 Mar 24;323(12):1151-1160. doi: 10.1001/jama.2020.1382.
PMID: 32207799
Abstract
IMPORTANCE:
It is unclear whether the number of steps per day and the intensity of stepping are associated with lower mortality.
OBJECTIVE:
Describe the dose-response relationship between step count and intensity and mortality.
DESIGN, SETTING, AND PARTICIPANTS:
Representative sample of US adults aged at least 40 years in the National Health and Nutrition Examination Survey who wore an accelerometer for up to 7 days ( from 2003-2006). Mortality was ascertained through December 2015.
EXPOSURES:
Accelerometer-measured number of steps per day and 3 step intensity measures (extended bout cadence, peak 30-minute cadence, and peak 1-minute cadence [steps/min]). Accelerometer data were based on measurements obtained during a 7-day period at baseline.
MAIN OUTCOMES AND MEASURES:
The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular disease (CVD) and cancer mortality. Hazard ratios (HRs), mortality rates, and 95% CIs were estimated using cubic splines and quartile classifications adjusting for age; sex; race/ethnicity; education; diet; smoking status; body mass index; self-reported health; mobility limitations; and diagnoses of diabetes, stroke, heart disease, heart failure, cancer, chronic bronchitis, and emphysema.
RESULTS:
A total of 4840 participants (mean age, 56.8 years; 2435 [54%] women; 1732 [36%] individuals with obesity) wore accelerometers for a mean of 5.7 days for a mean of 14.4 hours per day. The mean number of steps per day was 9124. There were 1165 deaths over a mean 10.1 years of follow-up, including 406 CVD and 283 cancer deaths. The unadjusted incidence density for all-cause mortality was 76.7 per 1000 person-years (419 deaths) for the 655 individuals who took less than 4000 steps per day; 21.4 per 1000 person-years (488 deaths) for the 1727 individuals who took 4000 to 7999 steps per day; 6.9 per 1000 person-years (176 deaths) for the 1539 individuals who took 8000 to 11 999 steps per day; and 4.8 per 1000 person-years (82 deaths) for the 919 individuals who took at least 12 000 steps per day. Compared with taking 4000 steps per day, taking 8000 steps per day was associated with significantly lower all-cause mortality (HR, 0.49 [95% CI, 0.44-0.55]), as was taking 12 000 steps per day (HR, 0.35 [95% CI, 0.28-0.45]). Unadjusted incidence density for all-cause mortality by peak 30 cadence was 32.9 per 1000 person-years (406 deaths) for the 1080 individuals who took 18.5 to 56.0 steps per minute; 12.6 per 1000 person-years (207 deaths) for the 1153 individuals who took 56.1 to 69.2 steps per minute; 6.8 per 1000 person-years (124 deaths) for the 1074 individuals who took 69.3 to 82.8 steps per minute; and 5.3 per 1000 person-years (108 deaths) for the 1037 individuals who took 82.9 to 149.5 steps per minute. Greater step intensity was not significantly associated with lower mortality after adjustment for total steps per day (eg, highest vs lowest quartile of peak 30 cadence: HR, 0.90 [95% CI, 0.65-1.27]; P value for trend = .34).
CONCLUSIONS AND RELEVANCE:
Based on a representative sample of US adults, a greater number of daily steps was significantly associated with lower all-cause mortality. There was no significant association between step intensity and mortality after adjusting for total steps per day.

Mortality of Japanese Olympic athletes: 1952-2017 cohort study.
Takeuchi T, Kitamura Y, Sado J, Hattori S, Kanemura Y, Naito Y, Nakajima K, Okuwaki T, Nakata K, Kawahara T, Sobue T.
BMJ Open Sport Exerc Med. 2019 Nov 13;5(1):e000653. doi: 10.1136/bmjsem-2019-000653. eCollection 2019.
PMID: 32206340
https://bmjopensem.bmj.com/content/bmjosem/5/1/e000653.full.pdf
Abstract
AIM:
To evaluate mortality among Japanese Olympic athletes compared with the general population and also evaluate their mortality based on total number of Olympics participation and intensity of sports disciplines.
METHODS:
Information on biography, vital status, date of birth, date of death and latest follow-up date on Japanese Olympians was retrieved from six online databases and compared. Standardised mortality ratio (SMR) was estimated according to observation periods and years from last participation in the Olympics. To further evaluate the association between mortality and total number of Olympics participation/intensity of sports disciplines within the study population, rate ratios (RRs) adjusted by sex, observation period and attained age group were estimated by a Poisson regression model.
RESULTS:
A total of 3381 Olympians were included in the analysis. The total person years was 94 076.82. The deaths of 153 (4.53%) Olympians were confirmed, and the overall SMR was 0.29 (95% CI, 0.25 to 0.34). SMRs categorised by years from last participation did not differ significantly. Higher mortality was observed among those who participated in the Olympics twice (RR: 1.52; 95% CI, 1.04 to 2.23) and three times or more (RR: 1.87; 95% CI, 1.08 to 3.25) compared with those who participated just once. Compared with combination of low static and low dynamic intensity category, higher mortality was observed in most combinations of middle-intensity or high-intensity categories.
CONCLUSION:
Japanese Olympians lived longer than the general population. More frequent participation in the Olympics and higher intensity of sports disciplines were associated with higher mortality.
KEYWORDS:
athlete; epidemiology; longevity; olympics

In Contrast to Dietary Restriction, Application of Resveratrol in Mice Does not Alter Mouse Major Urinary Protein Expression.
Pallauf K, Günther I, Chin D, Rimbach G.
Nutrients. 2020 Mar 19;12(3). pii: E815. doi: 10.3390/nu12030815.
PMID: 32204477
Abstract
Resveratrol (RSV) supplementation in mice has been discussed as partly mimicking the beneficial effects of dietary restriction (DR). However, data on putative benefits from resveratrol application in mice and other model organisms including humans is contradictory. Mouse major urinary proteins (MUPs) are a family of proteins that are expressed in rodent liver and secreted via urine. Impacting (mating) behavior and pheromone communication, they are severely down-regulated upon DR. We carried out two studies in C57BL/6Rj mice where RSV was either supplemented via diet or injected intraperitoneally for 8 weeks. Contrary to -40% DR, RSV did not decrease total MUP protein expression or Mup (amongst others Mup3, Mup5, Mup6, Mup15, and Mup20) mRNA levels in mouse liver when compared to ad-libitum (AL)-fed controls. Since inhibitory glucocorticoid response elements can be found in Mup promoters, we also measured glucocorticoid receptor (GR) levels in nuclear hepatic extracts. Consistent with differential MUP expression, we observed more nuclear GR in DR mice than in RSV-supplemented and AL control mice with no difference between RSV and AL. These findings point to the notion that, in mice, RSV does not mimic DR in terms of differential MUP expression.
KEYWORDS:
caloric restriction mimetic; glucocorticoid receptor; longevity

Adult weight gain and the risk of cardiovascular disease: a systematic review and dose-response meta-analysis of prospective cohort studies.
Jayedi A, Rashidy-Pour A, Soltani S, Zargar MS, Emadi A, Shab-Bidar S.
Eur J Clin Nutr. 2020 Mar 18. doi: 10.1038/s41430-020-0610-y. [Epub ahead of print] Review.
PMID: 32203236
Abstract
We aimed to examine the association of weight gain during adulthood with the risk of cardiovascular disease (CVD) in the general population. We performed a systematic search of PubMed and Scopus, from inception to June 2019. Prospective cohort studies investigating the association of weight gain during adulthood with the risk of CVD were included. The relative risks (RRs) were calculated by using random-effect models. Twenty-three prospective cohort studies with 1,093,337 participants were included. The RRs for a 5-kg increment in body weight were 1.11 (95% CI: 1.04, 1.19; I2 = 80%, n = 11) for CVD mortality, 1.18 (95% CI: 1.04, 1.32; I2 = 90%, n = 8) for coronary heart disease (CHD), 1.08 (95% CI: 1.04, 1.12; I2 = 0%, n = 3) for stroke, 1.18 (95% CI: 1.12, 1.25; I2 = 0%, n = 2) for myocardial infarction and 1.05 (95% CI: 0.86, 1.23; I2 = 80%, n = 2) for heart failure. A dose-response analysis demonstrated that the risk of CVD mortality was unchanged with weight gain of 0-5 kg, and then increased sharply and linearly (P for nonlinearity < 0.001). The analysis of CHD indicated a sharp increase in risk from baseline up to weight gain equal to 25 kg (P for nonlinearity = 0.12). Adult weight gain may be associated with a higher risk of CVD. Measuring weight gain during adulthood may be better than static, cross-sectional assessment of weight because it considers trend over time, and thus, can be used as a supplementary approach to predict CVD.

Lemon juice, but not tea, reduces the glycemic response to bread in healthy volunteers: a randomized crossover trial.
Freitas D, Boué F, Benallaoua M, Airinei G, Benamouzig R, Le Feunteun S.
Eur J Nutr. 2020 Mar 23. doi: 10.1007/s00394-020-02228-x. [Epub ahead of print]
PMID: 32201919
Abstract
PURPOSE:
The inhibition of enzymes that hydrolyze starch during digestion could constitute an opportunity to slow down the release, and ultimately the uptake, of starch-derived glucose. Simple dietary approaches consisting in pairing starch-rich foods with beverages that have the capacity to inhibit such enzymes could be an effective and easily implementable strategy. The objective of this work was to test the impact of black tea and lemon juice on the glycemic response to bread and subsequent energy intake in healthy adults.
METHODS:
A randomized crossover study was conducted with equal portions of bread (100 g) and 250 ml of water, black tea or lemon juice. Capillary blood glucose concentrations were monitored during 180 min using the finger-prick method. Ad libitum energy intake was assessed 3 h later.
RESULTS:
Tea had no effect on the glycemic response. Lemon juice significantly lowered the mean blood glucose concentration peak by 30% (p < 0.01) and delayed it more than 35 min (78 vs. 41 min with water, p < 0.0001). None of the tested beverages had an effect on ad libitum energy intake.
CONCLUSION:
These results are in agreement with previous in vitro studies showing that lowering the pH of a meal can slow down starch digestion through premature inhibition of salivary α-amylase. Furthermore, the effect of lemon juice was similar to what has been repeatedly observed with vinegar and other acidic foods. Including acidic beverages or foods in starchy meals thus appears to be a simple and effective strategy to reduce their glycemic impact.
KEYWORDS:
Acidity; Glycemic index; Salivary α-amylase; Satiety; Starch; Vinegar

Ten-year prospective evaluation of whole-body cancer screening with multiple modalities including [18F]fluorodeoxyglucose positron emission tomography in a healthy population.
Nishizawa S, Kojima S, Okada H, Shinke T, Torizuka T, Teramukai S, Fukushima M.
Ann Nucl Med. 2020 Mar 21. doi: 10.1007/s12149-020-01456-9. [Epub ahead of print]
PMID: 32200511
Abstract
PURPOSE:
To prospectively evaluate the value of whole-body cancer screening with multiple modalities including FDG-PET in a healthy population.
METHODS:
The study was conducted in 1197 healthy individuals aged ≥ 35 years at enrollment between August 2003 and July 2004. All participants were scheduled to receive annual whole-body cancer screening five times (screening period) with subsequent long-term follow-up (follow-up period). The endpoints of the study were definitive cancer diagnosis, cancer-related death, and all-cause death.
RESULTS:
The follow-up rate was 99.8% for the screening period and 96.2% for the follow-up period. Forty-five cancers were confirmed during the screening period (August 2003 to July 2009), and 37 of the 45 were detected by the screening. Fourteen of the 45 were PET positive. Sixteen, 5, 4, 9 and 11 cancers were confirmed after the first, the second, the third, the fourth, and the fifth (took 2 years) screening, respectively. Eight participants died, of whom five died of cancer. The rate of cancer incidence (per 100,000) of 628.7 (95% confidence interval [CI] 445.0-812.4) was significantly high, and the rates of cancer mortality and all-cause mortality of 69.9 (95% CI 8.6-131.1) and 111.8 (95% CI 34.3-189.2), respectively, were significantly low, compared with the corresponding rates of 379.3, 138.2 and 354.2, respectively, in the age-rank- and sex-matched general population. During the follow-up period (August 2009 to July 2013), 37 cancers were confirmed and 30 of the 37 were detected. Seven participants died, of whom three died of cancer. The rate of cancer incidence was 809.6 (95% CI 548.7-1070.5). The rates of cancer mortality and all-cause mortality of 65.6 (95% CI 0-139.9) and 153.2 (95% CI 39.7-266.6), respectively, were significantly low compared with 190.1 and 462.3, respectively, in the general population.
CONCLUSION:
Cancer detection by PET alone was limited. While the high cancer incidence was attributed to the extensive screening, the low cancer and all-cause mortality may indicate the potential value of this type of cancer screening. Cancer incidence increases with aging and it has been shown that continuous screening may reduce the risk caused by the cancer progression.
KEYWORDS:
CT; Cancer screening; FDG; MRI; PET; PET/CT

[AlPater]

The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials.
Kuang X, Liu C, Guo X, Li K, Deng Q, Li D.
Food Funct. 2020 Mar 27. doi: 10.1039/c9fo03063h. [Epub ahead of print]
PMID: 32219282
Abstract
BACKGROUND:
Previous studies did not draw a consistent conclusion about the effects of vitamin K combined with vitamin D on human skeletal quality.
METHOD AND FINDINGS:
A comprehensive search on Web of Science, PubMed, Embase and the Cochrane Library (from 1950 to February 2020) and bibliographies of relevant articles was undertaken, with the meta-analysis of eight randomized controlled trials (RCTs) including a total of 971 subjects. Vitamin K combined with vitamin D significantly increased the total bone mineral density (BMD): the pooled effect size was 0.316 [95% CI (confidence interval), 0.031 to 0.601]. A significant decrease in undercarboxylated osteocalcin (-0.945, -1.113 to -0.778) can be observed with the combination of vitamin K and D. Simultaneously, subgroup analysis showed that K2 or vitamin K (not specified) supplement was less than 500 μg d-1, which when combined with vitamin D can significantly increase the total BMD compared with the control group fed a normal diet or the group with no treatment (0.479, 0.101 to 0.858 and 0.570, 0.196 to 0.945).
CONCLUSIONS:
The combination of vitamin K and D can significantly increase the total BMD and significantly decrease undercarboxylated osteocalcin, and a more favorable effect is expected when vitamin K2 is used.

Shotgun Metagenomics of Gut Microbiota in Humans with up to Extreme Longevity and the Increasing Role of Xenobiotic Degradation.
Rampelli S, Soverini M, D'Amico F, Barone M, Tavella T, Monti D, Capri M, Astolfi A, Brigidi P, Biagi E, Franceschi C, Turroni S, Candela M.
mSystems. 2020 Mar 24;5(2). pii: e00124-20. doi: 10.1128/mSystems.00124-20.
PMID: 32209716
Abstract
The gut microbiome of long-lived people display an increasing abundance of subdominant species, as well as a rearrangement in health-associated bacteria, but less is known about microbiome functions. In order to disentangle the contribution of the gut microbiome to the complex trait of human longevity, we here describe the metagenomic change of the human gut microbiome along with aging in subjects with up to extreme longevity, including centenarians (aged 99 to 104 years) and semisupercentenarians (aged 105 to 109 years), i.e., demographically very uncommon subjects who reach the extreme limit of the human life span. According to our findings, the gut microbiome of centenarians and semisupercentenarians is more suited for xenobiotic degradation and shows a rearrangement in metabolic pathways related to carbohydrate, amino acid, and lipid metabolism. Collectively, our data go beyond the relationship between intestinal bacteria and physiological changes that occur with aging by detailing the shifts in the potential metagenomic functions of the gut microbiome of centenarians and semisupercentenarians as a response to progressive dietary and lifestyle modifications.IMPORTANCE The study of longevity may help us understand how human beings can delay or survive the most frequent age-related diseases and morbidities. In this scenario, the gut microbiome has been proposed as one of the variables to monitor and possibly support healthy aging. Indeed, the disruption of host-gut microbiome homeostasis has been associated with inflammation and intestinal permeability as well as a general decline in bone and cognitive health. Here, we performed a metagenomic assessment of fecal samples from semisupercentenarians, i.e., 105 to 109 years old, in comparison to young adults, the elderly, and centenarians, shedding light on the longest compositional and functional trajectory of the human gut microbiome with aging. In addition to providing a fine taxonomic resolution down to the species level, our study emphasizes the progressive age-related increase in degradation pathways of pervasive xenobiotics in Western societies, possibly as a result of a supportive process within the molecular continuum characterizing aging.
KEYWORDS:
aging; extreme longevity; metagenome; microbiome; xenobiotics

Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability.
Matsuno Y, Atsumi Y, Alauddin M, Rana MM, Fujimori H, Hyodo M, Shimizu A, Ikuta T, Tani H, Torigoe H, Nakatsu Y, Tsuzuki T, Komai M, Shirakawa H, Yoshioka KI.
Sci Rep. 2020 Mar 25;10(1):5388. doi: 10.1038/s41598-020-62292-5.
PMID: 32214146
Abstract
Genomic destabilisation is associated with the induction of mutations, including those in cancer-driver genes, and subsequent clonal evolution of cells with abrogated defence systems. Such mutations are not induced when genome stability is maintained; however, the mechanisms involved in genome stability maintenance remain elusive. Here, resveratrol (and related polyphenols) is shown to enhance genome stability in mouse embryonic fibroblasts, ultimately protecting the cells against the induction of mutations in the ARF/p53 pathway. Replication stress-associated DNA double-strand breaks (DSBs) that accumulated with genomic destabilisation were effectively reduced by resveratrol treatment. In addition, resveratrol transiently stabilised the expression of histone H2AX, which is involved in DSB repair. Similar effects on the maintenance of genome stability were observed for related polyphenols. Accordingly, we propose that polyphenol consumption can contribute to the suppression of cancers that develop with genomic instability, as well as lifespan extension.

Habitual tub bathing and risks of incident coronary heart disease and stroke.
Ukai T, Iso H, Yamagishi K, Saito I, Kokubo Y, Yatsuya H, Muraki I, Eshak ES, Sawada N, Tsugane S.
Heart. 2020 Mar 24. pii: heartjnl-2019-315752. doi: 10.1136/heartjnl-2019-315752. [Epub ahead of print]
PMID: 32209614
Abstract
OBJECTIVE:
Tub bathing is considered to have a preventive effect against cardiovascular disease (CVD) by improving haemodynamic function. However, no prospective studies have investigated the long-term effects of tub bathing with regard to CVD risk.
METHODS:
A total of 30 076 participants aged 40-59 years with no history of CVD or cancer were followed up from 1990 to 2009. Participants were classified by bathing frequency: zero to two times/week, three to four times/week and almost every day. The HRs of incident CVD were estimated using Cox proportional hazards models after adjusting for traditional CVD risk factors and selected dietary factors.
RESULTS:
During 538 373 person-years of follow-up, we documented a total of 2097 incident cases of CVD, comprising 328 coronary heart diseases (CHDs) (275 myocardial infarctions and 53 sudden cardiac deaths) and 1769 strokes (991 cerebral infarctions, 510 intracerebral haemorrhages, 255 subarachnoid haemorrhages and 13 unclassified strokes). The multivariable HRs (95% CIs) for almost daily or every day versus zero to two times/week were 0.72 (0.62 to 0.84, trend p<0.001) for total CVD; 0.65 (0.45 to 0.94, trend p=0.065) for CHD; 0.74 (0.62 to 0.87, trend p=0.005) for total stroke; 0.77 (0.62 to 0.97, trend p=0.467) for cerebral infarction; and 0.54 (0.40 to 0.73, trend p<0.001) for intracerebral haemorrhage. No associations were observed between tub bathing frequency and risk of sudden cardiac death or subarachnoid haemorrhage.
CONCLUSION:
The frequency of tub bathing was inversely associated with the risk of CVD among middle-aged Japanese.
KEYWORDS:
acute myocardial infarction; cardiac risk factors and prevention; stroke

Plasma magnesium and the risk of new-onset hyperuricemia in hypertensive patients.
Cao J, Zhang J, Zhang Y, Li H, Jiang C, Lin T, Zhou Z, Song Y, Liu C, Liu L, Wang B, Li J, Zhang Y, Cui Y, Huo Y, Wang X, Zhang H, Qin X, Xu X.
Br J Nutr. 2020 Mar 26:1-22. doi: 10.1017/S0007114520001099. [Epub ahead of print]
PMID: 32213225
Abstract
We aimed to evaluate the relationship of plasma magnesium with the risk of new-onset hyperuricemia, and examine any possible effect modifiers in hypertensive patients. This is a post-hoc analysis of the Uric acid (UA) Sub-study of the China Stroke Primary Prevention Trial (CSPPT). A total of 1685 participants were included in the current study. The main outcome was new-onset hyperuricemia defined as a UA concentration ≥417 μmol/L in men or ≥357 μmol/L in women. The secondary outcome was a change in UA concentration defined as UA at the exit visit minus that at baseline. During a median follow-up duration of 4.3 years, new-onset hyperuricemia occurred in 290 (17.2%) participants. There was a significantly inverse relation of plasma magnesium with the risk of new-onset hyperuricemia (per SD increment; OR, 0.85; 95%CI: 0.74, 0.99) and change in UA levels (per SD increment; β, -3.96 μmol/L; 95%CI: -7.14, -0.79). Consistently, when plasma magnesium was analyzed as tertiles, a significantly lower risk of new-onset hyperuricemia (OR, 0.67; 95%CI: 0.48, 0.95) and less increase in UA levels (β, -8.35μmol/L; 95%CI: -16.12, -0.58) were found among participants in tertile 3 (≥885.5 μmol/L) compared with those in tertile 1 (<818.9 μmol/L). Similar trends were found in males and females. Higher plasma magnesium levels were associated with a decreased risk of new-onset hyperuricemia in hypertensive adults.
KEYWORDS:
Magnesium; hypertensive patients; hyperuricemia; uric acid

The Dose-Response Relationship between Gamma-Glutamyl Transferase and Risk of Diabetes Mellitus Using Publicly Available Data: A Longitudinal Study in Japan.
Zhao W, Tong J, Liu J, Liu J, Li J, Cao Y.
Int J Endocrinol. 2020 Feb 21;2020:5356498. doi: 10.1155/2020/5356498. eCollection 2020.
PMID: 32215009
Abstract
PURPOSE:
The purpose of this study was to examine the association between baseline serum gamma-glutamyl transferase (GGT) and incident diabetes mellitus and to explore their dose-response relationship in a cohort of Japanese adults. Patients and Methods. Data were drawn from the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) study between 2004 and 2015, including hierarchical information on participants ≥18 years of age without diabetes mellitus, preexisting diabetes mellitus, heavy alcohol drinking, or other liver diseases (e.g., hepatitis B/C). The final analytic sample included 15464 participants, 373 of who were diagnosed as diabetes mellitus with a maximum 13-year follow-up. The risk of incident diabetes mellitus according to baseline serum GGT was estimated using multivariable Cox proportional hazards models and a two-piecewise linear regression model was developed to find out the threshold effect.
RESULTS:
Being in the highest quintile versus the lowest quintile of GGT levels was associated with an almost twofold increased risk of incident diabetes mellitus (hazard ratio 1.83 (95% CI 1.06, 3.15)), independent of age, gender, smoking status, alcohol intake, BMI, SBP, triglycerides, fatty liver, ALT, AST, and fasting plasma glucose. Further analysis revealed a positive curvilinear association between GGT and incident diabetes mellitus, with a saturation effect predicted at 24 IU/L. When serum GGT level was less than 24 IU/L, the risk of developing diabetes mellitus increased significantly with an increase in serum GGT levels (HR 1.04 (1.02, 1.07), P=0.0017). Besides, the association was more significant in nonsmoking participants than ex- or current-smokers (P=0.0017). Besides, the association was more significant in nonsmoking participants than ex- or current-smokers (P for interaction = 0.0378).
CONCLUSION:
Serum GGT level was a significant predictor of subsequent risk of diabetes mellitus, which increased by 4% for every 1 IU/L increase in GGT when GGT was less than 24 IU/L.
 

[AlPater]

A Prospective Evaluation of Serum Methionine-Related Metabolites in Relation to Pancreatic Cancer Risk in Two Prospective Cohort Studies.
Huang JY, Luu HN, Butler LM, Midttun Ø, Ulvik A, Wang R, Jin A, Gao YT, Tan Y, Ueland PM, Koh WP, Yuan JM.
Int J Cancer. 2020 Mar 29. doi: 10.1002/ijc.32994. [Epub ahead of print]
PMID: 32222976
Abstract
Deficiencies in methyl donor status may render DNA methylation changes and DNA damage, leading to carcinogenesis. Epidemiological studies reported that higher dietary intake of choline is associated with lower risk of pancreatic cancer, but no study has examined the association of serum choline and its metabolites with risk of pancreatic cancer. Two parallel case-control studies, one nested within the Shanghai Cohort Study (129 cases and 258 controls) and the other within the Singapore Chinese Health Study (58 cases and 104 controls), were conducted to evaluate the associations of baseline serum concentrations of choline, betaine, methionine, total methyl donors (i.e., sum of choline, betaine and methionine), dimethylglycine and trimethylamine N-oxide (TMAO) with pancreatic cancer risk. In the Shanghai cohort, odds ratios and 95% confidence intervals of pancreatic cancer for the highest quartile of choline, betaine, methionine, total methyl donors, and TMAO were 0.27 (0.11-0.69), 0.57 (0.31-1.05), 0.50 (0.26-0.96), 0.37 (0.19-0.73), and 2.81 (1.37-5.76), respectively, compared to the lowest quartile. The corresponding figures in the Singapore cohort were 0.85 (0.23-3.17), 0.50 (0.17-1.45), 0.17 (0.04-0.68), 0.33 (0.10-1.16), and 1.42 (0.50-4.04). The inverse associations of methionine and total methyl donors including choline, betaine and methionine with pancreatic cancer risk in both cohorts support that DNA repair and methylation play an important role against the development of pancreatic cancer. In the Shanghai cohort, TMAO, a gut microbiota-derived metabolite of dietary phosphatidylcholine, may contribute to higher risk of pancreatic cancer, suggesting a modifying role of gut microbiota in the dietary choline-pancreatic cancer risk association.
KEYWORDS:
DNA methylation; Pancreatic cancer; betaine; choline; methionine; microbiota; risk factors; trimethylamine N-oxide

Cytomegalovirus and cancer-related mortality in the national health and nutritional examination survey.
Okedele OO, Nelson HH, Oyenuga ML, Thyagarajan B, Prizment A.
Cancer Causes Control. 2020 Mar 28. doi: 10.1007/s10552-020-01296-y. [Epub ahead of print]
PMID: 32222844
Abstract
PURPOSE:
Cytomegalovirus (HCMV) is a common viral infection that shapes lifelong immunity. A history of infection with HCMV has been associated with many chronic diseases, including cancer. In addition, prospective cohort studies have established that HCMV is associated with all-cause mortality. However, there are limited data regarding HCMV and cancer mortality.
METHODS:
Data were obtained from the National Health and Nutrition Examination Survey (NHANES) III study (1988-1994): subjects aged 18 to 98, who had HCMV serology results, did not report having cancer at baseline, and were eligible for mortality follow-up (n = 14,498). Mortality was ascertained until December 2011 using National Death Index (NDI) linkage.
RESULTS:
The unadjusted risk of all-cancer mortality was higher in HCMV seropositive individuals (HR 2.74, 95% CI 2.05-3.64). This association was attenuated after adjusting for age (HR 1.39, 95% CI 1.02-1.92), and other covariates (age, sex, race/ethnicity, smoking status, BMI, education, and C-reactive protein (CRP); HR 1.21, 95% CI 0.91-1.81). There was a statistically significant interaction between HCMV and sex (p = 0.01): HCMV seropositivity was associated with increased cancer mortality in men (HR 1.65, 95% CI 0.99-2.73) but not in women (HR 0.95, 95% CI 0.59-1.54).
CONCLUSION(S):
Consistent with prior reports, HCMV seropositivity may be associated with an increased risk of cancer-related mortality but the association is partially driven by socioeconomic status and other risk factors. Future research is needed to determine whether HCMV is a risk factor for cancer, as well as identify the specific cancer types where HCMV increases mortality.
KEYWORDS:
Cancer; Cancer mortality; Cytomegalovirus; Mortality; Seropositivity

Plant-based and animal-based low-carbohydrate diets and risk of hepatocellular carcinoma among US men and women.
Liu Y, Yang W, VoPham T, Ma Y, Simon TG, Gao X, Chan AT, Meyerhardt JA, Giovannucci EL, Zhang X.
Hepatology. 2020 Mar 29. doi: 10.1002/hep.31251. [Epub ahead of print]
PMID: 32222996
Abstract
Little is known about the role of low-carbohydrate diets (LCDs) in the development of hepatocellular carcinoma (HCC). We prospectively evaluated the associations between plant-based and animal-based LCDs and risk of HCC in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Dietary intake was assessed every 4 years using validated food frequency questionnaires. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). HRs are shown for a 1-standard deviation (SD) increment with variable modelled as continuous. During 3,664,769 person years of follow-up, there were 156 incident HCC cases. Although there were no associations between overall or animal-based LCD score and risk of HCC, plant-based LCD score was inversely associated with HCC risk (HR: 0.83; 95% CI: 0.70-0.98; Ptrend =0.03). Carbohydrate intake, especially from refined grains (HR: 1.18; 95% CI: 1.00-1.39; Ptrend =0.04) was positively, while plant fat (HR: 0.78; 95% CI: 0.65-0.95; Ptrend =0.01) was inversely associated with HCC risk. Substituting 5% of energy from plant fat and protein for carbohydrate (HR: 0.74; 95% CI: 0.58-0.93; Ptrend =0.01) or refined grains (HR: 0.70; 95% CI: 0.55-0.90; Ptrend =0.006) was associated with lower HCC risk. In conclusion, a plant-based LCD and dietary restriction of carbohydrate from refined grains were associated with a lower risk of HCC. Substituting plant fat and protein for carbohydrate, particularly refined grains, may decrease HCC incidence. Our findings support a potential benefit in emphasizing plant sources of fat and protein in the diet for HCC primary prevention. Additional studies that carefully consider hepatitis B and C virus infections and chronic liver diseases are needed to confirm our findings.
KEYWORDS:
hepatocellular carcinoma; macronutrients; plant-based low-carbohydrate diets; prospective cohort; specific food sources

Association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance in older adults: National Health and nutrition examination Survey (NHANES) 2011-2014.
Dong X, Li S, Chen J, Li Y, Wu Y, Zhang D.
Nutr J. 2020 Mar 28;19(1):25. doi: 10.1186/s12937-020-00547-7.
PMID: 32222145
Abstract
BACKGROUND:
Current evidence on the association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance is inconsistent. Therefore, the aim is to explore the association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance in the U.S. noninstitutionalized population of older adults.
METHODS:
We used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Intakes of ω-3 and ω-6 fatty acids were obtained through two 24-h dietary recalls and were adjusted by energy. Cognitive performance was evaluated by the Consortium to Establish a Registry for Alzheimer's disease (CERAD) Word Learning sub-test, Animal Fluency test and Digit Symbol Substitution Test (DSST). For each cognitive test, people who scored lower than the lowest quartile in each age group were defined as having low cognitive performance. Binary logistic regression and restricted cubic spline models were applied to evaluate the association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance.
RESULTS:
A total of 2496 participants aged 60 years or older were included. In the full-adjusted model, the odds ratios (ORs) with 95% confidence interval (CI) of CERAD test score, Animal Fluency test score and DSST test score were 0.58 (0.38-0.88), 0.68 (0.47-0.99) and 0.59 (0.37-0.92) for the highest versus lowest tertile of dietary ω-3 fatty acids intake, respectively; the ORs with 95% CI of CERAD test score, Animal Fluency test score and DSST test score were 0.48 (0.31-0.75), 0.60 (0.40-0.92) and 0.50 (0.34-0.75) for the highest versus lowest tertile of dietary ω-6 fatty acids intake, respectively. The association between ω-6: ω-3 ratio and cognitive performance was not statistically significant in three tests. In dose-response relationship analysis, L-shaped associations were apparent for ω-3 and ω-6 fatty acids intake with CERAD test score, Animal Fluency test score and DSST test score.
CONCLUSIONS:
Dietary ω-3 and ω-6 fatty acids intake might be inversely associated with low cognitive performance.
KEYWORDS:
Cognitive performance; Dietary ω-3 fatty acids; Dietary ω-6 fatty acids; Dose-response; ω-6: ω-3 ratio

The effect of cinnamon supplementation on blood pressure in adults: A systematic review and meta-analysis of randomized controlled trials.
Hadi A, Campbell MS, Hassani B, Pourmasoumi M, Salehi-Sahlabadi A, Hosseini SA.
Clin Nutr ESPEN. 2020 Apr;36:10-16. doi: 10.1016/j.clnesp.2020.01.002. Epub 2020 Jan 20. Review.
PMID: 32220351
Abstract
BACKGROUND & AIMS:
Several clinical trials have shown that cinnamon can reduce blood pressure, but the results are controversial. Therefore, we conducted a systematic review and meta-analysis to provide a more precise estimate of the overall effects of cinnamon supplementation on blood pressure in adults.
METHODS:
We searched PubMed, Scopus, Cochrane Library, ISI Web of Science, and Google Scholar databases through September 2019 to identify randomized clinical trials (RCTs) investigating the effect of cinnamon supplementation on blood pressure. Data were pooled by using the random-effects model, and weighted mean difference (WMD) was considered as the summary effect size. Sensitivity analysis was conducted using the leave-one-out method.
RESULTS:
Meta-analysis of 9 RCTs with 641 participants showed significant reductions in both systolic (WMD: -5.17 mmHg, 95% CI: -9.35 to -0.99, P = 0.01) and diastolic blood pressure (WMD: -3.36 mmHg, 95% CI: -5.67 to -1.04, P ≤ 0.001) after cinnamon supplementation. Subgroup analyses indicated that these results were significant only when cinnamon was administered at the dosages of ≤2 g/day, for a period longer than 8 weeks, and in participants with a baseline BMI of ≥30 kg/m2.
CONCLUSION:
The present meta-analysis suggests that cinnamon supplementation can improve blood pressure by a modest degree. However, due to limited availability of studies with hypertensive cases and relatively small sample sizes of available studies, well designed trials with adequate sample sizes aimed at hypertensive populations are recommended.

Effect of dark chocolate on flow-mediated dilatation: Systematic review, meta-analysis, and dose-response analysis of randomized controlled trials.
Ebaditabar M, Djafarian K, Saeidifard N, Shab-Bidar S.
Clin Nutr ESPEN. 2020 Apr;36:17-27. doi: 10.1016/j.clnesp.2019.10.017. Epub 2019 Nov 16. Review.
PMID: 32220363
Abstract
BACKGROUND & AIMS:
We aimed to investigate the effect of dark chocolate on flow-mediated dilatation (FMD) using randomized clinical trials.
METHODS:
In order to find relevant papers, PubMed and Scopus were searched up to November 2018. Mean differences of eligible trials were pooled using random-effects models (the Der Simonian-Laird estimator). Subgroup analysis was conducted to assess the potential source of heterogeneity. Fractional polynomial modeling was used to explore dose-response relationships.
RESULTS:
Seventeen studies involving 615 participants assessed the effect of dark chocolate and six included studies involving 179 participants investigated the effect of flavonoids on FMD. Chronic consumption of dark chocolate and flavan-3-ols both increased FMD (0.69, 95% CI 0.22-1.16, p < 0.001, 1.16, 95% CI 0.52-1.80 p = 0.001, respectively). Pooling chronic consumption of dark chocolate and flavonoids improved FMD (p < 0.001) with significant heterogeneity among studies (p < 0.001; I2 = 64.2%). Type of intervention (flavonoid or cocoa, p = 0.230-dark chocolate, p < 0.001) was a source of heterogeneity. Also, we found that acute consumption of dark chocolate (p < 0.001) and both dark chocolate and flavonoids (p < 0.001) had beneficial effects on FMD. Consumption of flavonoids more than 40 g/day increases FMD with the highest mean of FMD in doses around 40-60 g/day. A non-linear dose-response has been also found after the chronic consumption of dark chocolate on FMD with a greater reduction in doses lower than 20 g/day.
CONCLUSION:
Current evidence indicated the beneficial effect of acute and chronic consumption of dark chocolate and flavonoids on FMD. Non-linear associations should be considered when investigating the effects of dietary intakes on FMD.
KEYWORDS:
Dark chocolate; Endothelial function; Flow mediated dilation; Meta-analysis

[AlPater]

Prospective Association between Whole Grain Consumption and Hypertension: The Furukawa Nutrition and Health Study.
Kashino I, Eguchi M, Miki T, Kochi T, Nanri A, Kabe I, Mizoue T.
Nutrients. 2020 Mar 26;12(4). pii: E902. doi: 10.3390/nu12040902.
PMID: 32224906
Abstract
Hypertension has become a major public health issue worldwide. Whole grains contain higher levels and a broader range of nutrients with potential health benefits and may decrease the risk of hypertension. However, no prospective studies have investigated this association in the high-income Asia Pacific region, which has the lowest whole grain intake worldwide. Thus, we examined the prospective association between whole grain consumption and the development of hypertension in Japan. Participants included 944 working Japanese adults aged 19-68 years who had no hypertension at baseline and completed a 3-year follow-up survey. Whole grain consumption was assessed via a self-administered dietary questionnaire. Multivariate logistic regression analysis was carried out to examine the association between whole grain consumption and hypertension, adjusting for potential confounding factors, such as sociodemographic, lifestyle, dietary, and occupational characteristics. After 3 years, 9.4% (86 cases) of the study participants had developed hypertension. More frequent whole grain consumption, classified as an intake frequency of "sometimes or always", was associated with lower odds of hypertension (multivariate-adjusted odds ratio: 0.36; 95% confidence interval: 0.16-0.83; p for trend = 0.04) compared with no consumption. Consuming more whole grains may decrease the risk of developing hypertension.
KEYWORDS:
Asians; Japan; blood pressure; cohort study; epidemiology; hypertension; whole grain

Prospective Associations of Accelerometer-Measured Physical Activity and Sedentary Time With Incident Cardiovascular Disease, Cancer, and All-Cause Mortality.
Dempsey PC, Strain T, Khaw KT, Wareham NJ, Brage S, Wijndaele K.
Circulation. 2020 Mar 31;141(13):1113-1115. doi: 10.1161/CIRCULATIONAHA.119.043030. Epub 2020 Mar 30. No abstract available.
PMID: 32223676
https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.119.043030

Handgrip strength is inversely associated with fatal cardiovascular and all-cause mortality events.
Laukkanen JA, Voutilainen A, Kurl S, Araujo CGS, Jae SY, Kunutsor SK.
Ann Med. 2020 Mar 30:1-25. doi: 10.1080/07853890.2020.1748220. [Epub ahead of print]
PMID: 32223654
Abstract
Purpose: We aimed to assess the associations of handgrip strength (HS) with cardiovascular and all-cause mortality and whether adding data on HS to cardiovascular disease (CVD) risk factors is associated with improvement in CVD mortality prediction.Design: Handgrip strength was assessed in a population-based sample of 861 participants aged 61-74 years at baseline. Relative HS was obtained by dividing the absolute value by body weight.Results: During a median (interquartile range) follow-up of 17.3 (12.6-18.4) years, 116 fatal coronary heart diseases (CHDs), 195 fatal CVDs, and 412 all-cause mortality events occurred. On adjustment for several risk factors, the hazard ratios (95% CIs) for fatal CHD, fatal CVD, and all-cause mortality were 0.59 (0.37-0.95), 0.59 (0.41-0.86), and 0.66 (0.51-0.84) respectively comparing extreme tertiles of relative HS. Adding relative HS to a CVD mortality risk prediction model containing established risk factors did not improve discrimination or reclassification using Harrel's C-index (C-index change: 0.0034; p = 0.65), integrated-discrimination-improvement (0.0059; p = 0.20), and net-reclassification-improvement (-1.31%; p = 0.74); however, there was a significant difference in in -2 log likelihood (p < 0.001).Conclusion: Relative HS is inversely associated with CHD, CVD and all-cause mortality events. Adding relative HS to conventional risk factors improves CVD risk assessment using sensitive measures of discrimination. KEY MESSAGESHandgrip strength assessment is simple, inexpensive and it takes only a few minutes to measure in clinical practice; however, its prognostic role for fatal cardiovascular outcomes on top of traditional risk factors in apparently healthy populations is uncertain.In a population-based prospective cohort study, good handgrip strength adjusted for body weight was associated with lower risk of fatal cardiovascular outcomes and the associations remained consistent across several clinically relevant subgroups.Handgrip strength may be a useful prognostic tool for fatal CHD and CVD events, in the general population.
KEYWORDS:
cardiovascular disease; handgrip strength; mortality; risk prediction

CirculationVol. 139, No. Suppl_1
ORAL ABSTRACT PRESENTATIONS
SESSION TITLE: EPIDEMIOLOGY OF MAJOR CARDIOVASCULAR EVENTS
Abstract 007: Actigraphy-Measured Sleep Regularity and Risk of Incident Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis
Tianyi Huang, Sara Mariani, Susan Redline
Originally published6 Mar 2019https://doi.org/10.1161/circ.139.suppl_1.007Circulation. 2019;139:A007
Abstract
Background: Prior studies have linked rotating night shift work to increased risk of cardiovascular disease (CVD). Irregular sleep schedules, characterized by high day-to-day variability in sleep duration or timing, represent possibly milder but much more common/chronic disruption of circadian rhythms in the general population. However, no prospective study to date has examined the association between sleep regularity and CVD outcomes.
Methods: In the Multi-Ethnic Study of Atherosclerosis, 1,993 participants who were free of CVD completed 7-day wrist actigraphy at home for objective monitoring of sleep duration and quality between 2010 and 2013, and were prospectively followed through 2015. We assessed sleep regularity using the standard deviation (SD) of actigraphy-measured sleep duration and sleep onset timing across 7 days. Incident CVD was defined as total cardiovascular events including coronary heart disease, stroke, congestive heart failure, and cardiovascular death. Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for incident CVD according to SD of sleep duration and timing, adjusted for traditional CVD risk factors (e.g., sociodemographic factors, lifestyles and CVD biomarkers) and other sleep-related factors (e.g., average sleep duration, insomnia symptoms, daytime sleepiness, sleep-disordered breathing, chronotype and work schedules).
Results: During a median follow-up of 4.0 years, 95 participants developed CVD events. Compared to participants with a 7-day sleep duration SD ≤60 min, the multivariable-adjusted HR (95% CI) for CVD was 1.12 (0.61, 2.07) for 61-90 min, 1.71 (0.94, 3.09) for 91-120 min, and 2.20 (1.22, 3.96) for >120 min. Every 1-hour increase in sleep duration SD was associated with 23% higher CVD risk (95% CI: 1.05, 1.45; p-trend=0.01). In contrast to this linear association with sleep duration variability, there appeared to be a threshold pattern for the association with SD of sleep onset timing. Compared to participants with a sleep timing SD ≤30 min, the multivariable-adjusted HR (95% CI) for CVD was 1.13 (0.60, 2.13) for 31-60 min, 1.15 (0.58, 2.31) for 61-90 min, and 2.07 (1.09, 3.94) for >90 min. CVD risk was 87% higher comparing sleep timing SD >90 min versus ≤90 min (95% CI: 1.19, 2.96; p=0.007). These associations did not differ significantly by age, sex, race/ethnicity, sleep duration or work schedules. Exclusion of current shift workers yielded similar results.
Conclusion: Irregular sleep duration and timing may be novel risk factors for CVD, independent of traditional CVD risk factors and sleep quantity/quality. Given the increased prevalence of irregular sleep (e.g., due to mobile device use), our findings have important public health implications for CVD prevention and suggest value in evaluating the impact of sleep hygiene interventions aimed at improving sleep pattern consistency.
>>>>>>>>>>>>>>>>>>
Sleep Irregularity and Risk of Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis.
Huang T, Mariani S, Redline S.
J Am Coll Cardiol. 2020 Mar 10;75(9):991-999. doi: 10.1016/j.jacc.2019.12.054.
PMID: 32138974
Abstract
BACKGROUND:
The cardiovascular system exhibits strong circadian rhythms to maintain normal functioning. Irregular sleep schedules, characterized by high day-to-day variability in sleep duration or timing, represent possibly milder but much more common and chronic disruption of circadian rhythms in the general population than shift work.
OBJECTIVES:
This study aimed to prospectively examine the association between sleep regularity and risk of cardiovascular disease (CVD).
METHODS:
In MESA (Multi-Ethnic Study of Atherosclerosis), 1,992 participants free of CVD completed 7-day wrist actigraphy for sleep assessment from 2010 to 2013 and were prospectively followed through 2016. The study assessed sleep regularity using the SD of actigraphy-measured sleep duration and sleep-onset timing across 7 days. Incident CVD included nonfatal and fatal cardiovascular events. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for incident CVD according to SD of sleep duration and timing, adjusted for traditional CVD risk factors (including CVD biomarkers) and other sleep-related factors (including average sleep duration).
RESULTS:
During a median follow-up of 4.9 years, 111 participants developed CVD events. The multivariable-adjusted HRs (95% confidence intervals) for CVD across categories of sleep duration SD were 1.00 (reference) for ≤60 min, 1.09 (0.62 to 1.92) for 61 to 90 min, 1.59 (0.91 to 2.76) for 91 to 120 min, and 2.14 (1.24 to 3.68) for >120 min (p trend = 0.002). Similarly, compared with participants with a sleep timing SD ≤30 min, the HRs (95% confidence intervals) for CVD were 1.16 (0.64 to 2.13) for 31 to 60 min, 1.52 (0.81 to 2.88) for 61 to 90 min, and 2.11 (1.13 to 3.91) for >90 min (p trend = 0.002). Exclusion of current shift workers yielded similar results.
CONCLUSIONS:
Irregular sleep duration and timing may be novel risk factors for CVD, independent of traditional CVD risk factors and sleep quantity and/or quality.
KEYWORDS:
cardiovascular disease; circadian rhythms; cohort study; risk factor; sleep patterns

[AlPater]

Dietary diversity and all-cause mortality among Chinese adults aged 65 or older: A community-based cohort study.
Tao L, Xie Z, Huang T.
Asia Pac J Clin Nutr. 2020;29(1):152-160. doi: 10.6133/apjcn.202003_29(1).0020.
PMID: 32229454
Abstract
BACKGROUND AND OBJECTIVES:
To evaluate the association between dietary diversity and all-cause mortality in older adults.
METHODS AND STUDY DESIGN:
17,949 community-based elderly participants aged ≥65 years in China were included in this cohort study. The baseline consumption frequencies of nine food groups (meat, vegetables, fish, eggs, fruits, legumes, milk, tea, and nuts) were recorded, and the dietary diversity score (0-9) was calculated. Survival status and death date were collected during follow-up. Cox proportional-hazards models were used to assess the association between dietary diversity and all-cause mortality.
RESULTS:
We identified 8445 death events over 57,685 person-years of follow-up. Compared with participants in the lowest dietary diversity score group (score 0-1), higher dietary diversity scores were associated with lower mortality risk in univariate models. After adjusting for potential confounders, participants in the higher dietary diversity score group had a 9%-30% lower risk in all-cause mortality (p trend <0.001) compared with those in the lowest dietary diversity score group. The inverse relationship between dietary diversity score and all-cause mortality was also significant in four food groups (vegetables, fish, fruits, and nuts). Similar results were observed in sensitivity analyses.
CONCLUSIONS:
Our study showed that dietary diversity was inversely associated with all-cause mortality in the Chinese elderly, especially in the oldest old and men. Therefore, increasing dietary diversity may reduce mortality rates in the older population, and tailored interventions for improving dietary diversity are required to benefit health and survival in them.

Self-rated health and objective health status as predictors of all-cause mortality among older people: a prospective study with a 5-, 10-, and 27-year follow-up.
Wuorela M, Lavonius S, Salminen M, Vahlberg T, Viitanen M, Viikari L.
BMC Geriatr. 2020 Mar 30;20(1):120. doi: 10.1186/s12877-020-01516-9.
PMID: 32228464
Abstract
BACKGROUND:
Despite a non-specific nature of self-rated health (SRH), it seems to be a strong predictor of mortality. The aim of this study is to assess the association of SRH and objective health status (OH) with all-cause mortality in 70-year-old community-dwelling older people in Finland.
METHODS:
A prospective study with 5-, 10- and 27-year follow-ups. SRH (n = 1008) was assessed with a single question and OH (n = 962) by the Rockwood's Frailty Index (FI). To assess the association of SRH and OH with mortality, Cox regression model was used.
RESULTS:
Of the 1008 participants, 138 (13.7%), 319 (31.6%), and 932 deceased (86.3%) during the 5-, 10- and 27-year follow-ups, respectively. In unadjusted models, subjects with poor SRH had almost eightfold risk for mortality compared to those with good SRH during the 5-year follow-up; among those with poor OH, the risk was fourfold compared to those with good OH. In the 10-year-follow up, both poor SRH and poor OH predicted about fourfold risk for mortality compared to those with good health. During the 27-year follow-up, OH was a stronger predictor of mortality than SRH. Poor SRH, compared to good SRH, showed 95% sensitivity and 34% specificity for 5-year mortality; corresponding figures for OH were 54 and 80%, respectively.
CONCLUSIONS:
Single-item SRH seems to be able to capture almost the same as OH in predicting a short-term (less than 10 years) mortality risk among older adults in clinical settings. The use of SHR may also enhance the focus on patient-centered care.
KEYWORDS:
Frailty; Mortality; Objective health; Older people; Self-rated health

Vitamin D and liver cancer risk: A meta-analysis of prospective studies.
Guo XF, Zhao T, Han JM, Li S, Li D.
Asia Pac J Clin Nutr. 2020;29(1):175-182. doi: 10.6133/apjcn.202003_29(1).0023.
PMID: 32229457
Abstract
BACKGROUND AND OBJECTIVES:
The association between circulating vitamin D and liver cancer risk has been controversial on the basis of epidemiological studies. The aim of this study was to quantitatively evaluate this association with prospective studies.
METHODS AND STUDY DESIGN:
A systematic literature search was implemented in PubMed and Scopus databases up to June 2019. Using a random-effects model, the multivariate-adjusted relative risks (RRs) with corresponding 95% confidence interval (CI) were pooled for the highest versus lowest category. Trend estimation was conducted with a two-stage dose-response meta-analysis.
RESULTS:
Six independent prospective studies (992 liver cancer events and 60,811 participants) were included for data synthesis. The summary estimate showed that a higher circulating vitamin D was associated with lower risk of liver cancer (Summary RR=0.78; 95% CI: 0.63, 0.95; I2=53.6%, p=0.035). Dose-response analysis indicated that liver cancer was associated with 8% (95% CI: 0.89, 0.95) lower risk with a 10 nmol/L increment of circulating vitamin D concentration.
CONCLUSIONS:
The present study provides substantial evidence that a higher concentration of circulating vitamin D would have conferred protection against liver cancer.

The Role of Protein Intake and its Timing on Body Composition and Muscle Function in Healthy Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Wirth J, Hillesheim E, Brennan L.
J Nutr. 2020 Mar 31. pii: nxaa049. doi: 10.1093/jn/nxaa049. [Epub ahead of print]
PMID: 32232404
Abstract
BACKGROUND:
Increased protein intake has been suggested to improve gains in muscle mass and strength in adults. Furthermore, the timing of protein intake has been discussed as a margin of opportunity for improved prevention measures.
OBJECTIVE:
This systematic review investigated the effect of protein supplementation on body composition and muscle function (strength and synthesis) in healthy adults, with an emphasis on the timing of protein intake.
METHODS:
Randomized controlled trials were identified using PubMed, Web of Science, CINAHL, and Embase, up to March 2019. For meta-analyses, data on lean body mass (LBM), handgrip strength, and leg press strength were pooled by age group (mean age 18-55 or >55 y) and timing of protein intake. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach.
RESULTS:
Data from 65 studies with 2907 participants (1514 men and 1380 women, 13 unknown sex) were included in the review. Twenty-six, 8, and 24 studies were used for meta-analysis on LBM, handgrip strength, and leg press strength, respectively. The protein supplementation was effective in improving (mean difference; 95% CI) LBM in adults (0.62 kg; 0.36, 0.88) and older adults (0.46 kg; 0.23, 0.70), but not handgrip strength (older adults: 0.26 kg; -0.51, 1.04) and leg press strength (adults: 5.80 kg; -0.33, 11.93; older adults: 1.97 kg; -2.78, 6.72). Sensitivity analyses removing studies without exercise training had no impact on the outcomes. Data regarding muscle synthesis were scarce and inconclusive. Subgroup analyses showed no beneficial effect of a specific timing of protein intake on LBM, handgrip strength, and leg press strength.
CONCLUSION:
Overall, the results support the positive impact of protein supplementation on LBM of adults and older adults, independently of intake timing. Effects on muscle strength and synthesis are less clear and need further investigation. This systematic review was registered on PROSPERO as CRD42019126742.
KEYWORDS:
adults; body composition; elderly; lean body mass; muscle strength; muscle synthesis; obese; protein; timing of intake

Effects of Leucine Administration in Sarcopenia: A Randomized and Placebo-controlled Clinical Trial.
Martínez-Arnau FM, Fonfría-Vivas R, Buigues C, Castillo Y, Molina P, Hoogland AJ, van Doesburg F, Pruimboom L, Fernández-Garrido J, Cauli O.
Nutrients. 2020 Mar 27;12(4). pii: E932. doi: 10.3390/nu12040932.
PMID: 32230954
Abstract
Treating sarcopenia in older individuals remains a challenge, and nutritional interventions present promising approaches in individuals that perform limited physical exercise. We assessed the efficacy of leucine administration to evaluate whether the regular intake of this essential amino acid can improve muscle mass, muscle strength and functional performance and respiratory muscle function in institutionalized older individuals. The study was a placebo-controlled, randomized, double-blind design in fifty participants aged 65 and over (ClinicalTrials.gov identifier NCT03831399). The participants were randomized to a parallel group intervention of 13 weeks' duration with a daily intake of leucine (6 g/day) or placebo (lactose, 6 g/day). The primary outcome was to study the effect on sarcopenia and respiratory muscle function. The secondary outcomes were changes in the geriatric evaluation scales, such as cognitive function, functional impairment and nutritional assessments. We also evaluated whether leucine administration alters blood analytical parameters and inflammatory markers. Administration of leucine was well-tolerated and significantly improves some criteria of sarcopenia in elderly individuals such as functional performance measured by walking time (p = 0.011), and improved lean mass index. For respiratory muscle function, the leucine-treated group improved significantly (p = 0.026) in maximum static expiratory force compared to the placebo. No significant effects on functional impairment, cognitive function or nutritional assessment, inflammatory cytokines IL-6, TNF-alpha were observed after leucine administration compared to the placebo. The use of l-leucine supplementation can have some beneficial effects on sarcopenia and could be considered for the treatment of sarcopenia in older individuals.
KEYWORDS:
elderly; muscle mass; muscle strength; nutrition; respiratory muscles; sarcopenia

Effects of Diet on Sleep: A Narrative Review.
Binks H, E Vincent G, Gupta C, Irwin C, Khalesi S.
Nutrients. 2020 Mar 27;12(4). pii: E936. doi: 10.3390/nu12040936. Review.
PMID: 32230944
Abstract
Many processes are involved in sleep regulation, including the ingestion of nutrients, suggesting a link between diet and sleep. Aside from studies investigating the effects of tryptophan, previous research on sleep and diet has primarily focused on the effects of sleep deprivation or sleep restriction on diet. Furthermore, previous reviews have included subjects with clinically diagnosed sleep-related disorders. The current narrative review aimed to clarify findings on sleep-promoting foods and outline the effects of diet on sleep in otherwise healthy adults. A search was undertaken in August 2019 from the Cochrane, MEDLINE (PubMed), and CINAHL databases using the population, intervention, control, outcome (PICO) method. Eligible studies were classified based on emerging themes and reviewed using narrative synthesis. Four themes emerged: tryptophan consumption and tryptophan depletion, dietary supplements, food items, and macronutrients. High carbohydrate diets, and foods containing tryptophan, melatonin, and phytonutrients (e.g., cherries), were linked to improved sleep outcomes. The authors posit that these effects may be due in part to dietary influences on serotonin and melatonin activity.
KEYWORDS:
adults; dietary supplements; food; nutrients; sleep duration; sleep quality