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AlPater

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  1. Thyroid function and risk of all-cause and cardiovascular mortality: a prospective population-based cohort study. Groothof D, Flores-Guerrero JL, Nolte IM, Bouma HR, Gruppen EG, Bano A, Post A, Kootstra-Ros JE, Hak E, Bos JHJ, de Borst MH, Gans ROB, Links TP, Dullaart RPF, Bakker SJL. Endocrine. 2020 Jul 6. doi: 10.1007/s12020-020-02397-z. Online ahead of print. PMID: 32632723 https://link.springer.com/content/pdf/10.1007/s12020-020-02397-z.pdf Abstract Purpose: Although thyroid hormones are irrefutably implicated in cardiovascular physiology, the impact of within-reference range variations of thyroid function on cardiovascular disease (CVD) remains unclear. Elucidating this is important, since it could foster preventive treatment and reduce global CVD burden. We therefore investigated the impact of within-reference range variations of thyroid function on all-cause and cardiovascular mortality. Methods: We included community-dwelling individuals aged 28-75 years from a prospective cohort study, without known use of thyroid-affecting therapy and with thyrotropin within reference range. Associations of thyroid function with mortality were quantified using Cox models and adjusted for sociodemographic and cardiovascular risk factors. Results: Mean (SD) age of the 6,054 participants (52.0% male) was 53.3 (12.0) years. During 47,594 person-years of follow-up, we observed 380 deaths from all causes and 103 from CVDs. Although higher thyrotropin was not associated with all-cause mortality (adjusted HR 1.02, 95% CI 0.92-1.14), point estimates for cardiovascular mortality diverged toward increased risk in younger (<72 years) participants (1.31, 1.00-1.72) and decreased risk in elderly (≥72 years) (0.77, 0.56-1.06). Higher free thyroxine (FT4) was associated with all-cause mortality (1.18, 1.07-1.30) and with cardiovascular mortality only in elderly (1.61, 1.19-2.18), but not in younger participants (1.03, 0.78-1.34). Higher free triiodothyronine (FT3) was associated with all-cause mortality in females only (1.18, 1.02-1.35). FT3 was not associated with cardiovascular mortality (0.91, 0.70-1.18). Conclusions: Community-dwelling elderly individuals with high-normal thyroid function are at increased risk of all-cause and cardiovascular mortality, reinforcing the need of redefining the current reference ranges of thyroid function. Keywords: Biomarker; Cohort study; Euthyroid; General population; Mortality risk; Thyroid function. Association of Statin Use With All-Cause and Cardiovascular Mortality in US Veterans 75 Years and Older. Orkaby AR, Driver JA, Ho YL, Lu B, Costa L, Honerlaw J, Galloway A, Vassy JL, Forman DE, Gaziano JM, Gagnon DR, Wilson PWF, Cho K, Djousse L. JAMA. 2020 Jul 7;324(1):68-78. doi: 10.1001/jama.2020.7848. PMID: 32633800 Abstract Importance: Data are limited regarding statin therapy for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in adults 75 years and older. Objective: To evaluate the role of statin use for mortality and primary prevention of ASCVD in veterans 75 years and older. Design, setting, and participants: Retrospective cohort study that used Veterans Health Administration (VHA) data on adults 75 years and older, free of ASCVD, and with a clinical visit in 2002-2012. Follow-up continued through December 31, 2016. All data were linked to Medicare and Medicaid claims and pharmaceutical data. A new-user design was used, excluding those with any prior statin use. Cox proportional hazards models were fit to evaluate the association of statin use with outcomes. Analyses were conducted using propensity score overlap weighting to balance baseline characteristics. Exposures: Any new statin prescription. Main outcomes and measures: The primary outcomes were all-cause and cardiovascular mortality. Secondary outcomes included a composite of ASCVD events (myocardial infarction, ischemic stroke, and revascularization with coronary artery bypass graft surgery or percutaneous coronary intervention). Results: Of 326 981 eligible veterans (mean [SD] age, 81.1 [4.1] years; 97% men; 91% white), 57 178 (17.5%) newly initiated statins during the study period. During a mean follow-up of 6.8 (SD, 3.9) years, a total 206 902 deaths occurred including 53 296 cardiovascular deaths, with 78.7 and 98.2 total deaths/1000 person-years among statin users and nonusers, respectively (weighted incidence rate difference [IRD]/1000 person-years, -19.5 [95% CI, -20.4 to -18.5]). There were 22.6 and 25.7 cardiovascular deaths per 1000 person-years among statin users and nonusers, respectively (weighted IRD/1000 person-years, -3.1 [95 CI, -3.6 to -2.6]). For the composite ASCVD outcome there were 123 379 events, with 66.3 and 70.4 events/1000 person-years among statin users and nonusers, respectively (weighted IRD/1000 person-years, -4.1 [95% CI, -5.1 to -3.0]). After propensity score overlap weighting was applied, the hazard ratio was 0.75 (95% CI, 0.74-0.76) for all-cause mortality, 0.80 (95% CI, 0.78-0.81) for cardiovascular mortality, and 0.92 (95% CI, 0.91-0.94) for a composite of ASCVD events when comparing statin users with nonusers. Conclusions and relevance: Among US veterans 75 years and older and free of ASCVD at baseline, new statin use was significantly associated with a lower risk of all-cause and cardiovascular mortality. Further research, including from randomized clinical trials, is needed to more definitively determine the role of statin therapy in older adults for primary prevention of ASCVD. A Comparison of Mortality-related Risk Factors of COVID-19, SARS, and MERS: A Systematic Review and Meta-analysis. Lu L, Zhong W, Bian Z, Li Z, Zhang K, Liang B, Zhong Y, Hu M, Lin L, Liu J, Lin X, Huang Y, Jiang J, Yang X, Zhang X, Huang Z. J Infect. 2020 Jul 4:S0163-4453(20)30460-6. doi: 10.1016/j.jinf.2020.07.002. Online ahead of print. PMID: 32634459 Review. Abstract Objective: Coronavirus Disease 2019 (COVID-19) is a pandemic. This systematic review compares mortality risk factors including clinical, demographic and laboratory features of COVID-19, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The aim is to provide new strategies for COVID-19 prevention and treatment. Methods: We performed a systematic review with meta-analysis, using five databases to compare the predictors of death for COVID-19, SARS and MERS. A random-effects model meta-analysis calculated odds ratios (OR) and 95% confidence intervals (95% CI). Results: 845 articles up through 11/4/2020 were retrieved, but only 28 studies were included in this meta-analysis. The results showed that males had a higher likelihood of death than females (OR = 1.82, 95% CI 1.56-2.13). Age (OR = 7.86, 95% CI 5.46-11.29), diabetes comorbidity (OR = 3.73, 95% CI 2.35-5.90), chronic lung disease (OR = 3.43, 95% CI 1.80-6.52) and hypertension (OR = 3.38, 95% CI 2.45-4.67) were the mortality risk factors. The laboratory indicators lactic dehydrogenase (OR = 37.52, 95% CI 24.68-57.03), C-reactive protein (OR = 12.11, 95% CI 5.24-27.98), and neutrophils (OR = 17.56, 95% CI 10.67-28.90) had stronger correlations with COVID-19 mortality than with SARS or MERS mortality. Consolidation and ground-glass opacity imaging features were similar among COVID-19, SARS, and MERS patients. Conclusions: COVID-19's mortality factors are similar to those of SARS and MERS. Age and laboratory indicators could be effective predictors of COVID-19 mortality outcomes. Keywords: COVID-19; MERS; Meta-analysis; Mortality; Risk factors; SARS. Effect of cinnamon on migraine attacks and inflammatory markers: A randomized double-blind placebo-controlled trial. Zareie A, Sahebkar A, Khorvash F, Bagherniya M, Hasanzadeh A, Askari G. Phytother Res. 2020 Jul 7. doi: 10.1002/ptr.6721. Online ahead of print. PMID: 32638445 Abstract Migraine is the most common type of primary headaches. Increased levels of interleukin-6 (IL-6), calcitonin-gene-related peptide (CGRP) and nitric oxide (NO) lead to inflammation and neurogenic pain. Cinnamon has anti-inflammatory and neuroprotective properties. Thus, the aim of this study was to assess the effect of cinnamon on migraine attacks and inflammatory status. Fifty patients with migraine were randomized to receive either cinnamon powder (three capsules/day each containing 600 mg of cinnamon) or three placebo capsules/day each containing 100 mg of corn starch (control group) for 2 months. Serum levels of IL-6, CGRP and NO were measured at baseline and at the end of the study. The frequency, severity and duration of pain attacks were also recorded using questionnaire. Serum concentrations of IL-6 and NO were significantly reduced in the cinnamon group compared with the control group (p < .05). However, serum levels of CGRP remained unchanged in both groups. The frequency, severity and duration of migraine attacks were significantly decreased in the cinnamon group compared with the control group. Cinnamon supplementation reduced inflammation as well as frequency, severity and duration of headache in patients with migraine. Cinnamon could be regarded as a safe supplement to relieve pain and other complications of migraine. Keywords: calcitonin-gene-related; cinnamon; interleukin-6; migraine; nitric oxide. Dietary Fatty Acids and Colorectal Cancer Risk in Men: A Report from the Shanghai Men's Health Study and a Meta-Analysis. Nguyen S, Li H, Yu D, Cai H, Gao J, Gao Y, Luu H, Tran H, Xiang YB, Zheng W, Shu XO. Int J Cancer. 2020 Jul 7. doi: 10.1002/ijc.33196. Online ahead of print. PMID: 32638381 Abstract Evidence from animal models suggests that dietary fatty acids have both anticancer and tumor-promoting effects. Whether dietary fatty acids are associated with colorectal cancer (CRC) in humans remains inconclusive. We investigated associations between dietary fatty acids and risk of CRC among 59,986 men who participated in the Shanghai Men's Health Study (SMHS), an ongoing population-based prospective cohort study. We identified 876 incident CRC cases in the SMHS during a mean follow-up of 9.8 years. Associations between dietary fatty acid intake and CRC risk were evaluated by Cox proportional hazard regression analyses. Consumption of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids was not significantly associated with CRC risk. Multivariate hazard ratios (HR) and respective 95% confidence intervals (CI) for quartile 4 vs. quartile 1 were 0.92 (0.74-1.14; Ptrend =0.47) for SFA, 0.95 (0.79-1.16; Ptrend =0.74) for MUFA and 1.18 (0.95-1.46; Ptrend =0.21) for PUFA. No significant association was found for total n-6 PUFA and total n-3 PUFA. Additionally, we performed a meta-analysis to summarize results from the present study and 28 reports from 26 additional cohorts, which supported the overall null association between dietary fatty acid intake and CRC risk among men. Docosahexanoic acid (DHA) and eicosapentaenoic acid (EPA) were associated with 11-12% reduced risk, and linoleic acid (LA) a 19% increased risk, of CRC in the meta-analysis of combined sexes. In conclusion, this population-based prospective study and meta-analysis of cohort studies found little evidence that dietary fatty acid intake was associated with risk of CRC in men. Keywords: Colorectal cancer; Dietary fatty acid; Meta-analysis; Prospective cohort study. Hypertension and changes in cognitive function in a Mediterranean population. Razquin C, Menéndez-Acebal C, Cervantes S, Martínez-González MA, Vázquez-Ruiz Z, Martínez-González J, Guillén-Grima F, Toledo E. Nutr Neurosci. 2020 Jul 7:1-9. doi: 10.1080/1028415X.2020.1788773. Online ahead of print. PMID: 32635835 Abstract Background: Severe cognitive decline is one of the major public health problems in developed countries. Finding modifiable risk factors could become essential to develop strategies to prevent or delay dementia progression and stop its rising incidence. Objective: Our aim was to investigate the association between hypertension and cognitive function and to assess whether better adherence to the Mediterranean diet may modify this association. Methods: A subsample of 764 participants from the 'Seguimiento Universidad de Navarra' (SUN) cohort older than 55 years was evaluated with the Spanish Telephone Interview for Cognitive Status (TICS-m) at two-time points, separated by 6 years. Multivariable-adjusted linear regression models were used to prospectively assess the association between hypertension -also according to adherence to the Mediterranean diet- and 6-y changes in cognitive function. Results: The adjusted between-group difference in the 6-year change of the TICS-m score between hypertensive participants and their non-hypertensive counterparts was -0.36 (95% CI -0.70, -0.02). This association was stronger among participants with a lower adherence to the Mediterranean diet [-0.62 (95% CI: -1.09, -0.15)] but the differences between hypertensive and non-hypertensive participants were no longer significant among participants with a higher baseline adherence to the Mediterranean diet. Conclusion: In this Mediterranean cohort, hypertension was inversely associated with cognitive function, but an attenuation of this detrimental association by a moderate/high adherence to the Mediterranean diet was suggested. Keywords: Cognitive decline; Mediterranean diet; SUN cohort; cognitive function; cognitive screening test; dementia; hypertension; primary prevention. C. elegans ACAT regulates lipolysis and its related lifespan in fasting through modulation of the genes in lipolysis and insulin/IGF-1 signaling. Bai J, Farias-Pereira R, Zhang Y, Jang M, Park Y, Kim KH. Biofactors. 2020 Jul 8. doi: 10.1002/biof.1666. Online ahead of print. PMID: 32639091 Abstract Overly active acyl-coenzyme A: cholesterol acyltransferases (ACATs) are known to contribute to the development of atherosclerosis, cancer cell proliferation and de novo lipogenesis. However, the role of ACAT in systemic lipid metabolism and its consequence of aging is unknown. Using avasimibe, a clinically proven ACAT inhibitor, and mboa-1 mutant strain, a homologous to mammalian ACAT, herein, we found that Ava treatment and mboa-1 mutant exhibited a decreased fat accumulation during feeding and increased lipolysis with extended lifespan of C. elegans during fasting. Our study highlights the essential role of ACAT inhibitor and mboa-1 in fat mobilization and the survival of C. elegans in fasting through the modulation of the genes involved in lipolysis and insulin/IGF-1 signaling. Keywords: C. elegans; MBOA-1; avasimibe; fasting; lifespan. Impact of Influenza Vaccination on Mortality in the Oldest Old: A Propensity Score-Matched Cohort Study. Walzer P, Estève C, Barben J, Menu D, Cuenot C, Manckoundia P, Putot A. Vaccines (Basel). 2020 Jul 3;8(3):E356. doi: 10.3390/vaccines8030356. PMID: 32635210 Abstract Influenza remains a major cause of illness and death in geriatric populations. While the influenza vaccine has successfully reduced morbidity and mortality, its effectiveness is suspected to decrease with age. The aim of this study was to assess the impact of influenza vaccination on all-cause mortality in very old ambulatory subjects. We conducted a prospective cohort study from 1 July 2016 to 31 June 2017 in a large unselected ambulatory population aged over 80 years. We compared all-cause mortality in vaccinated versus unvaccinated subjects after propensity-score matching, to control for age, sex and comorbidities. Among the 9149 patients included, with mean age 86 years, 4380 (47.9%) were vaccinated against influenza. In total, 5253 (57.4%) had at least one chronic disease. The most commonly vaccinated patients were those with chronic respiratory failure (76.3%) and the least commonly vaccinated were those suffering from Parkinson's disease (28.5%). Overall, 2084 patients (22.8%) died during the study. After propensity score matching, the mortality was evaluated at 20.9% in the vaccinated group and 23.9% in the unvaccinated group (OR = 0.84 [0.75-0.93], p = 0.001). This decrease in mortality in the vaccinated group persisted whatever the age and Charlson Comorbidity index. In conclusion, nearly a half of this ambulatory elderly population received Influenza vaccine. After adjustment on comorbidities, influenza vaccination was associated with a significant decrease in all-cause mortality, even in the eldest multimorbid population. Improving immunization coverage in this frail older population is urgently needed. Keywords: comorbidities; elderly; flu; influenza; influenza vaccination; mortality; multimorbidity. Nutritional Aspects of Spermidine. Madeo F, Hofer SJ, Pendl T, Bauer MA, Eisenberg T, Carmona-Gutierrez D, Kroemer G. Annu Rev Nutr. 2020 Jul 7. doi: 10.1146/annurev-nutr-120419-015419. Online ahead of print. PMID: 32634331 Abstract Natural polyamines (spermidine and spermine) are small, positively charged molecules that are ubiquitously found within organisms and cells. They exert numerous (intra)cellular functions and have been implicated to protect against several age-related diseases. Although polyamine levels decline in a complex age-dependent, tissue-, and cell type-specific manner, they are maintained in healthy nonagenarians and centenarians. Increased polyamine levels, including through enhanced dietary intake, have been consistently linked to improved health and reduced overall mortality. In preclinical models, dietary supplementation with spermidine prolongs life span and health span. In this review, we highlight salient aspects of nutritional polyamine intake and summarize the current knowledge of organismal and cellular uptake and distribution of dietary (and gastrointestinal) polyamines and their impact on human health. We further summarize clinical and epidemiological studies of dietary polyamines. Integrated metabolomics reveals altered lipid metabolism in adipose tissue in a model of extreme longevity. Darcy J, Fang Y, McFadden S, Lynes MD, Leiria LO, Dreyfuss JM, Bussburg V, Tolstikov V, Greenwood B, Narain NR, Kiebish MA, Bartke A, Tseng YH. Geroscience. 2020 Jul 6. doi: 10.1007/s11357-020-00221-0. Online ahead of print. PMID: 32632845 Abstract Adipose tissue plays an essential role in metabolic health. Ames dwarf mice are exceptionally long-lived and display metabolically beneficial phenotypes in their adipose tissue, providing an ideal model for studying the intersection between adipose tissue and longevity. To this end, we assessed the metabolome and lipidome of adipose tissue in Ames dwarf mice. We observed distinct lipid profiles in brown versus white adipose tissue of Ames dwarf mice that are consistent with increased thermogenesis and insulin sensitivity, such as increased cardiolipin and decreased ceramide concentrations. Moreover, we identified 5-hydroxyeicosapentaenoic acid (5-HEPE), an ω-3 fatty acid metabolite, to be increased in Ames dwarf brown adipose tissue (BAT), as well as in circulation. Importantly, 5-HEPE is increased in other models of BAT activation and is negatively correlated with body weight, insulin resistance, and circulating triglyceride concentrations in humans. Together, these data represent a novel lipid signature of adipose tissue in a mouse model of extreme longevity. Keywords: Aging; Ames dwarf; Beige adipose tissue; Brown adipose tissue; Lipidomics; Metabolomics; Thermogenesis. Health benefits of xylitol. Gasmi Benahmed A, Gasmi A, Arshad M, Shanaida M, Lysiuk R, Peana M, Pshyk-Titko I, Adamiv S, Shanaida Y, Bjørklund G. Appl Microbiol Biotechnol. 2020 Jul 7. doi: 10.1007/s00253-020-10708-7. Online ahead of print. PMID: 32638045 Review. Abstract Many diseases, including caries, chronic inflammatory diseases, diabetes, and obesity, are associated with uncontrolled sugar consumption. Artificial sweeteners are commonly used in food and pharmaceutical industries as sugar substitutes for the prevention of several dental and body diseases; they also have a favorable impact on body weight as they may help to restrict simple sugar consumption. Xylitol is a sugar alcohol that is commonly used as a sweetener. It can be found naturally or artificially prepared mainly from plant materials chemically or by fermentation of hemicelluloses from agricultural biomass by yeast or bacteria strains. This polyol has a significant antiplaque effect on teeth surface and can reduce the gingival inflammation; it is being used as a preventive agent for dental caries due to decreasing the growth levels of pathogenic Streptococcus mutans and Streptococcus sangui at the very early stages. Xylitol can bind with calcium ion leading to consequent remineralization of teeth enamel; it is also able to prevent osteoporosis. This polyol can treat respiratory tract and middle ear diseases due to its antibacterial and anti-inflammatory potential and prevent some diseases which cannot be cured through antibiotics or surgery. Xylitol can reduce constipation, diabetes, obesity, and other body syndromes or illnesses; it has also revealed its stimulating effect on digestion and immune system. However, it can produce some side effects such as irritable bowel syndrome, diarrhea, nephrolithiasis, etc., when consumed in excessive amounts. Different vehicles are used for delivering the xylitol into the human body, but chewing gums occupy a leading position. The present review is devoted to comprehensive analyses of the positive and negative effects of this polyol on human health.Key Points• The health benefits of xylitol are not limited to oral hygiene.• Xylitol efficiently stimulates the immune system, digestion, lipid and bone metabolism.• Xylitol helps in glycemic and obesity control; reduces ear and respiratory infections.• Xylitol treats diseases that cannot be cured through antibiotics or by surgery. Keywords: Artificial sweetener; Caries; Health care; Metabolic disease; Oral microbiota; Preventive effect; Xylitol.
  2. AlPater

    Al's CR updates

    Calorie restriction promotes remyelination in a Cuprizone-Induced demyelination mouse model of multiple sclerosis. Mojaverrostami S, Pasbakhsh P, Madadi S, Nekoonam S, Zarini D, Noori L, Shiri E, Salama M, Zibara K, Kashani IR. Metab Brain Dis. 2020 Jul 7. doi: 10.1007/s11011-020-00597-0. Online ahead of print. PMID: 32638202 Abstract Over the past few decades several attempts have been made to introduce a potential and promising therapy for Multiple sclerosis (MS). Calorie restriction (CR) is a dietary manipulation to reduce calorie intake which has been shown to improve neuroprotection and attenuate neurodegenerative disorders. Here, we evaluated the effect of 33% CR regimen for 4 weeks on the remyelination capacity of Cuprizone (CPZ) induced demyelination in a mouse model of MS. Results showed that CR induced a significant increase in motor coordination and balance performance in CPZ mice. Also, luxol fast blue (LFB) staining showed that CR regimen significantly improved the remyelination in the corpus callosum of CPZ + CR mice compared to the CPZ group. In addition, CR regimen significantly increased the transcript expression levels of BDNF, Sox2, and Sirt1 in the corpus callosum of CPZ mice, while decreasing the p53 levels. Moreover, CR regimen significantly decreased the apoptosis rate. Furthermore, astrogliosis (GFAP + astrocytes) and microgliosis (Iba-1 + microglia) were significantly decreased by CR regimen while oligodendrogenesis (Olig2+) and Sirt1 + cell expression were significantly increased in the corpus callosum of CPZ + CR mice compared to the CPZ group. In conclusion, CR regimen can promote remyelination potential in a CPZ-demyelinating mouse model of MS by increasing oligodendrocyte generation while decreasing their apoptosis. Keywords: Calorie restriction; Cuprizone; Demyelination; Multiple sclerosis; Remyelination. Lifespan Extension Via Dietary Restriction: Time to Reconsider the Evolutionary Mechanisms? Moatt JP, Savola E, Regan JC, Nussey DH, Walling CA. Bioessays. 2020 Jul 8:e1900241. doi: 10.1002/bies.201900241. Online ahead of print. PMID: 32638410 Abstract Dietary restriction (DR) is the most consistent environmental manipulation to extend lifespan. Originally thought to be caused by a reduction in caloric intake, recent evidence suggests that macronutrient intake underpins the effect of DR. The prevailing evolutionary explanations for the DR response are conceptualized under the caloric restriction paradigm, necessitating reconsideration of how or whether these evolutionary explanations fit this macronutrient perspective. In the authors' opinion, none of the current evolutionary explanations of DR adequately explain the intricacies of observed results; instead a context-dependent combination of these theories is suggested which is likely to reflect reality. In reviewing the field, it is proposed that the ability to track the destination of different macronutrients within the body will be key to establishing the relative roles of the competing theories. Understanding the evolution of the DR response and its ecological relevance is critical to understanding variation in DR responses and their relevance outside laboratory environments. Keywords: adaptive plasticity; geometric framework of nutrition; nutrient recycling; resource reallocation; toxic protein; trade-off.
  3. Association of Rapid Eye Movement Sleep With Mortality in Middle-aged and Older Adults. Leary EB, Watson KT, Ancoli-Israel S, Redline S, Yaffe K, Ravelo LA, Peppard PE, Zou J, Goodman SN, Mignot E, Stone KL. JAMA Neurol. 2020 Jul 6. doi: 10.1001/jamaneurol.2020.2108. Online ahead of print. PMID: 32628261 Abstract Importance: Rapid eye movement (REM) sleep has been linked with health outcomes, but little is known about the relationship between REM sleep and mortality. Objective: To investigate whether REM sleep is associated with greater risk of mortality in 2 independent cohorts and to explore whether another sleep stage could be driving the findings. Design, setting, and participants: This multicenter population-based cross-sectional study used data from the Outcomes of Sleep Disorders in Older Men (MrOS) Sleep Study and Wisconsin Sleep Cohort (WSC). MrOS participants were recruited from December 2003 to March 2005, and WSC began in 1988. MrOS and WSC participants who had REM sleep and mortality data were included. Analysis began May 2018 and ended December 2019. Main outcomes and measures: All-cause and cause-specific mortality confirmed with death certificates. Results: The MrOS cohort included 2675 individuals (2675 men [100%]; mean [SD] age, 76.3 [5.5] years) and was followed up for a median (interquartile range) of 12.1 (7.8-13.2) years. The WSC cohort included 1386 individuals (753 men [54.3%]; mean [SD] age, 51.5 [8.5] years) and was followed up for a median (interquartile range) of 20.8 (17.9-22.4) years. MrOS participants had a 13% higher mortality rate for every 5% reduction in REM sleep (percentage REM sleep SD = 6.6%) after adjusting for multiple demographic, sleep, and health covariates (age-adjusted hazard ratio, 1.12; fully adjusted hazard ratio, 1.13; 95% CI, 1.08-1.19). Results were similar for cardiovascular and other causes of death. Possible threshold effects were seen on the Kaplan-Meier curves, particularly for cancer; individuals with less than 15% REM sleep had a higher mortality rate compared with individuals with 15% or more for each mortality outcome with odds ratios ranging from 1.20 to 1.35. Findings were replicated in the WSC cohort despite younger age, inclusion of women, and longer follow-up (hazard ratio, 1.13; 95% CI, 1.08-1.19). A random forest model identified REM sleep as the most important sleep stage associated with survival. Conclusions and relevance: Decreased percentage REM sleep was associated with greater risk of all-cause, cardiovascular, and other noncancer-related mortality in 2 independent cohorts. Helicobacter pylori eradication for the prevention of gastric neoplasia. Ford AC, Yuan Y, Forman D, Hunt R, Moayyedi P. Cochrane Database Syst Rev. 2020 Jul 6;7:CD005583. doi: 10.1002/14651858.CD005583.pub3. PMID: 32628791 Review. Abstract Background: Gastric cancer is the third most common cause of cancer death worldwide. Individuals infected with Helicobacter pylori have a higher likelihood of developing gastric cancer than individuals who are not infected. Eradication of H. pylori in healthy asymptomatic individuals in the general population may reduce the incidence of gastric cancer, but the magnitude of this effect is unclear. Objectives: To assess the effectiveness of eradication of H. pylori in healthy asymptomatic individuals in the general population in reducing the incidence of gastric cancer. Search methods: We identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 1), MEDLINE (1946 to February 2020), and EMBASE (1974 to February 2020). We handsearched reference lists from trials selected by electronic searching to identify further relevant trials. We handsearched published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) between 2001 and 2019. We contacted members of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. Selection criteria: We analysed randomised controlled trials comparing at least one week of H. pylori therapy with placebo or no treatment in preventing subsequent development of gastric cancer in otherwise healthy and asymptomatic H. pylori-positive adults. Trials had to follow up participants for at least two years and needed to have at least two participants with gastric cancer as an outcome. We defined gastric cancer as any gastric adenocarcinoma, including intestinal (differentiated) or diffuse (undifferentiated) type, with or without specified histology. Data collection and analysis: We collected data on incidence of gastric cancer, incidence of oesophageal cancer, deaths from gastric cancer, deaths from any cause, and adverse effects arising due to therapy. Main results: Six trials met all our eligibility criteria and provided extractable data in the previous version. Following our updated search, one new RCT was identified, meaning that seven trials were included in this updated review. In addition, one previously included trial provided fully published data out to 10 years, and another previously included trial provided fully published data out to 22 years of follow-up. Four trials were at low risk of bias, one trial was at unclear risk, and two trials were at high risk of bias. Six trials were conducted in Asian populations. In preventing development of subsequent gastric cancer, H. pylori eradication therapy was superior to placebo or no treatment (RR 0.54, 95% confidence interval (CI) 0.40 to 0.72, 7 trials, 8323 participants, moderate certainty evidence). Only two trials reported the effect of eradication of H. pylori on the development of subsequent oesophageal cancer. Sixteen (0.8%) of 1947 participants assigned to eradication therapy subsequently developed oesophageal cancer compared with 13 (0.7%) of 1941 participants allocated to placebo (RR 1.22, 95% CI 0.59 to 2.54, moderate certainty evidence). H. pylori eradication reduced mortality from gastric cancer compared with placebo or no treatment (RR 0.61, 95% CI 0.40 to 0.92, 4 trials, 6301 participants, moderate certainty evidence). There was little or no evidence in all-cause mortality (RR 0.97, 95% CI 0.85 to 1.12, 5 trials, 7079 participants, moderate certainty evidence). Adverse events data were poorly reported. Authors' conclusions: We found moderate certainty evidence that searching for and eradicating H. pylori reduces the incidence of gastric cancer and death from gastric cancer in healthy asymptomatic infected Asian individuals, but we cannot necessarily extrapolate this data to other populations. Relationships between serum uric acid concentrations, uric acid lowering medications, and vertebral fracture in community-dwelling elderly Japanese men: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Cohort Study. Iki M, Yura A, Fujita Y, Kouda K, Tachiki T, Tamaki J, Sato Y, Moon JS, Hamada M, Kajita E, Okamoto N, Kurumatani N. Bone. 2020 Jul 2:115519. doi: 10.1016/j.bone.2020.115519. Online ahead of print. PMID: 32622874 Abstract Purpose: The association between serum concentrations of uric acid (UA), a potent endogenous antioxidant, and fracture risk has not yet been examined for morphometric vertebral fracture (VF). This study aimed to determine whether serum UA concentrations are associated with risks of clinical osteoporotic fracture (OPF) and morphometric VF after adjusting for confounding factors including UA-lowering medications (ULMs). Materials and methods: A total of 2012 Japanese men aged ≥65 years completed the baseline study, which included serum UA measurement and X-ray absorptiometry-based VF assessment. We conducted a follow-up study five years later to identify incident OPFs and VFs. OPF was identified through interviews. Incident VF was defined as a vertebra which showed reduction in any of its anterior, central, or posterior heights by ≥20% during follow-up, and satisfied grade one or higher fracture criteria in Genant's method on follow-up images. Bone mineral density (BMD) of the hip and spine was measured by dual-energy X-ray absorptiometry at baseline and follow-up. Results: We identified 45 clinical OPFs from 2000 men and 39 VFs from 1530 men during a mean follow-up period of 4.3 years. Hip BMD was significantly higher in higher UA concentration groups after adjusting for age and body mass index. A significantly decreased multivariate-adjusted odds ratio (OR) of incident VF was observed for the highest quartile groups of serum UA concentrations compared with the lowest quartile group (OR: 0.17, 95% confidence interval: 0.05-0.62). This OR remained significant after further adjusting for ULM use. ULM users in the lowest quartile group of serum UA concentrations had a significantly higher incidence rate of VF compared to the other quartile groups. Conclusions: Higher serum UA concentrations were associated with a lower risk of morphometric VF independently of ULM in Japanese elderly men. Excessive reduction of serum UA concentrations by ULM might increase VF risk. Keywords: Gout; Morphometric vertebral fracture; Osteoporotic fracture; Population-based prospective cohort study; Serum uric acid concentration; Uric acid lowering medication. Estimated 24-Hour Urinary Sodium Excretion and Incident Cardiovascular Disease and Mortality Among 398 628 Individuals in UK Biobank. Elliott P, Muller DC, Schneider-Luftman D, Pazoki R, Evangelou E, Dehghan A, Neal B, Tzoulaki I. Hypertension. 2020 Jul 6:HYPERTENSIONAHA11914302. doi: 10.1161/HYPERTENSIONAHA.119.14302. Online ahead of print. PMID: 32623924 https://sci-hub.tw/10.1161/HYPERTENSIONAHA.119.14302 Abstract We report on an analysis to explore the association between estimated 24-hour urinary sodium excretion (surrogate for sodium intake) and incident cardiovascular disease (CVD) and mortality. Data were obtained from 398 628 UK Biobank prospective cohort study participants (40-69 years) recruited between 2006 and 2010, with no history of CVD, renal disease, diabetes mellitus or cancer, and cardiovascular events and mortality recorded during follow-up. Hazard ratios between 24-hour sodium excretion were estimated from spot urinary sodium concentrations across incident CVD and its components and all-cause and cause-specific mortality. In restricted cubic splines analyses, there was little evidence for an association between estimated 24-hour sodium excretion and CVD, coronary heart disease, or stroke; hazard ratios for CVD (95% CIs) for the 15th and 85th percentiles (2.5 and 4.2 g/day, respectively) compared with the 50th percentile of estimated sodium excretion (3.2 g/day) were 1.05 (1.01-1.10) and 0.96 (0.92-1.00), respectively. An inverse association was observed with heart failure, but that was no longer apparent in sensitivity analysis. A J-shaped association was observed between estimated sodium excretion and mortality. Our findings do not support a J-shaped association of estimated sodium excretion with CVD, although such an association was apparent for all-cause and cause-specific mortality across a wide range of diseases. Reasons for these differences are unclear; methodological limitations, including the use of estimating equations based on spot urinary data, need to be considered in interpreting our findings. Keywords: blood pressure; cardiovascular diseases; mortality; risk; sodium. Dietary Potassium Downregulates Angiotensin-I Converting Enzyme, Renin, and Angiotensin Converting Enzyme 2. Vio CP, Gallardo P, Cespedes C, Salas D, Diaz-Elizondo J, Mendez N. Front Pharmacol. 2020 Jun 18;11:920. doi: 10.3389/fphar.2020.00920. eCollection 2020. PMID: 32625100 Free PMC article. Abstract Background: The importance of dietary potassium in health and disease has been underestimated compared with that placed on dietary sodium. Larger effort has been made on reduction of sodium intake and less on the adequate dietary potassium intake, although natural food contains much more potassium than sodium. The benefits of a potassium-rich diet are known, however, the mechanism by which it exerts its preventive action, remains to be elucidated. With the hypothesis that dietary potassium reduces renal vasoconstrictor components of the renin-angiotensin system in the long-term, we studied the effect of high potassium diet on angiotensin-I converting enzyme, renin, and angiotensin converting enzyme 2. Methods: Sprague Dawley male rats on a normal sodium diet received normal potassium (0.9%, NK) or high potassium diet (3%, HK) for 4 weeks. Urine was collected in metabolic cages for electrolytes and urinary volume measurement. Renal tissue was used to analyze angiotensin-I converting enzyme, renin, and angiotensin converting enzyme 2 expression. Protein abundance analysis was done by Western blot; gene expression by mRNA levels by RT-qPCR. Renal distribution of angiotensin-I converting enzyme and renin was done by immunohistochemistry and morphometric analysis in coded samples. Results: High potassium diet (4 weeks) reduced the levels of renin, angiotensin-I converting enzyme, and angiotensin converting enzyme 2. Angiotensin-I converting enzyme was located in the brush border of proximal tubules and with HK diet decreased the immunostaining intensity (P < 0.05), decreased the mRNA (P < 0.01) and the protein levels (P < 0.01). Renin localization was restricted to granular cells of the afferent arteriole and HK diet decreased the number of renin positive cells (P < 0.01) and renin mRNA levels (P < 0.01). High potassium intake decreased angiotensin converting enzyme 2 gene expression and protein levels (P < 0.01).No morphological abnormalities were observed in renal tissue during high potassium diet.The reduced expression of angiotensin-I converting enzyme, renin, and angiotensin converting enzyme 2 during potassium supplementation suggest that high dietary potassium intake could modulate these vasoactive enzymes and this effects can contribute to the preventive and antihypertensive effect of potassium. Keywords: angiotensin converting enzyme 2 (ACE2); angiotensin-I converting enzyme (ACE); dietary potassium intake; immunohistochemistry; renin. Glycemic load, dietary fiber, and added sugar and fecundability in 2 preconception cohorts. Willis SK, Wise LA, Wesselink AK, Rothman KJ, Mikkelsen EM, Tucker KL, Trolle E, Hatch EE. Am J Clin Nutr. 2020 Jul 1;112(1):27-38. doi: 10.1093/ajcn/nqz312. PMID: 31901163 Abstract Background: Glycemic load (GL) reflects the quantity and quality of carbohydrates in the diet; dietary fiber and added sugar are components of GL. Few epidemiologic studies have assessed the association between these dietary factors and fecundability. Objective: We prospectively evaluated the associations of GL, total carbohydrates, dietary fiber, and added sugar with fecundability. Methods: Snart Foraeldre (SF) and Pregnancy Study Online (PRESTO) are parallel web-based prospective preconception cohorts of couples attempting to conceive in Denmark and North America. At baseline, female participants completed a web-based questionnaire on demographic and lifestyle factors and a validated FFQ. We calculated GL, total carbohydrate intake, total dietary fiber, carbohydrate-to-fiber ratio, and added sugar based on reported frequencies for individual foods, standard recipes for mixed foods, and average serving sizes. The analysis included 2709 SF participants and 4268 PRESTO participants. We used proportional probabilities regression models to estimate fecundability ratios (FR) and 95% CIs. Results: Compared with an average daily GL of ≤100, FRs for an average daily GL of ≥141 were 0.89 (95% CI: 0.73, 1.08) in SF and 0.87 (95% CI: 0.77, 0.98) in PRESTO participants. Compared with consuming ≤16 g/d of dietary fiber, FRs for consuming ≥25 g/d were 0.99 (95% CI: 0.81, 1.22) in SF and 1.06 (95% CI: 0.94, 1.20) in PRESTO. Compared with a carbohydrate-to-fiber ratio of ≤8, FRs for a ratio of ≥13 were 0.86 (95% CI: 0.73, 1.01) in SF and 0.87 (95% CI: 0.78, 0.98) in PRESTO. Compared with ≤27 g/d of added sugar, FRs for ≥72 g/d were 0.87 (95% CI: 0.68, 1.10) in SF and 0.86 (95% CI: 0.75, 0.99) in PRESTO participants. Conclusions: Among women attempting to conceive in Denmark and North America, diets high in GL, carbohydrate-to-fiber ratio, and added sugar were associated with modestly reduced fecundability. Keywords: added sugar; carbohydrate; dietary fiber; fecundability; glycemic load; time-to-pregnancy. >>>>>>>>>>>>>>>>>>> Carbohydrates and fertility: just the tip of the (fertility) iceberg. Chavarro JE. Am J Clin Nutr. 2020 Jul 1;112(1):1-2. doi: 10.1093/ajcn/nqaa039. PMID: 32119733 No abstract available. https://sci-hub.tw/10.1093/ajcn/nqaa039
  4. AlPater

    Al's CR updates

    Aerobic capacity modulates adaptive thermogenesis: Contribution of non-resting energy expenditure. Mukherjee SD, Koch LG, Britton SL, Novak CM. Physiol Behav. 2020 Jul 3:113048. doi: 10.1016/j.physbeh.2020.113048. Online ahead of print. PMID: 32628949 https://sci-hub.tw/http://www.sciencedirect.com/science/article/pii/S0031938420303620 Abstract Decreases in energy stores requires negative energy balance where caloric expenditure exceeds energy intake, which can induce adaptive thermogenesisࣧthe reduction of energy expenditure (EE) beyond that accounted for by the weight lost. Adaptive thermogenesis varies between individuals. The component of total daily EE responsible for the interindividual variation in adaptive thermogenesis was investigated in this study, using a rat model that differs in obesity propensity and physical activity. Total daily EE and physical activity were examined before and after 21 days of 50% calorie restriction in male and female rats with lean and obesity-prone phenotypesࣧrats selectively bred for high and low intrinsic aerobic capacity (HCR and LCR, respectively). Calorie restriction significantly decreased EE more than was predicted by loss of weight and lean mass, demonstrating adaptive thermogenesis. Within sex, HCR and LCR did not significantly differ in resting EE. However, the calorie restriction-induced suppression in non-resting EE, which includes activity EE, was significantly greater in HCR than in LCR; this phenotypic difference was significant for both male and female rats. Calorie restriction also significantly suppressed physical activity levels more in HCR than LCR. When VO2max was assessed in male rats, calorie restriction significantly decreased O2 consumption without significantly affecting running performance (running time, distance), indicating increased energy efficiency. Percent weight loss did not significantly differ between groups. Altogether, these results suggest that individual differences in calorie restriction-induced adaptive thermogenesis may be accounted for by variation in aerobic capacity. Moreover, it is likely that activity EE, not resting or basal metabolism, may explain or predict the variation in individuals' adaptive thermogenesis. Keywords: LCR); Non-exercise activity thermogenesis (NEAT); Physical activity; energy expenditure; high- and low-capacity runners (HCR; obesity. Does Calorie Restriction Modulate Inflammaging via FoxO Transcription Factors? Kim SE, Mori R, Shimokawa I. Nutrients. 2020 Jun 30;12(7):E1959. doi: 10.3390/nu12071959. PMID: 32630045 Review. Abstract Calorie restriction (CR) has been shown to extend lifespan and retard aging-related functional decline in animals. Previously, we found that the anti-neoplastic and lifespan-extending effects of CR in mice are regulated by forkhead box O transcription factors (FoxO1 and FoxO3), located downstream of growth hormone (GH)-insulin-like growth factor (IGF)-1 signaling, in an isoform-specific manner. Inflammaging is a term coined to represent that persistent low-level of inflammation underlies the progression of aging and related diseases. Attenuation of inflammaging in the body may underlie the effects of CR. Recent studies have also identified cellular senescence and activation of the nucleotide-binding domain, leucine-rich-containing family, pyrin-domain-containing-3 (NLRP3) inflammasome as causative factors of inflammaging. In this paper, we reviewed the current knowledge of the molecular mechanisms linking the effects of CR with the formation of inflammasomes, particularly focusing on possible relations with FoxO3. Inflammation in the brain that affects adult neurogenesis and lifespan was also reviewed as evidence of inflammaging. A recent progress of microRNA research was described as regulatory circuits of initiation and propagation of inflammaging. Finally, we briefly introduced our preliminary results obtained from the mouse models, in which Foxo1 and Foxo3 genes were conditionally knocked out in the myeloid cell lineage. Keywords: FoxO; NLRP3 inflammasome; calorie restriction; cellular senescence; inflammaging.
  5. Oops, did not notice your post, Gordo, I searched for the authors. Anyway, maybe the below pertains too: Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020 Daniel M. Weinberger, PhD1; Jenny Chen, BS2; Ted Cohen, MD, DPH1; Forrest W. Crawford, PhD3,4; Farzad Mostashari, MD5; Don Olson, MPH6; Virginia E. Pitzer, ScD1; Nicholas G. Reich, PhD7; Marcus Russi, BS1; Lone Simonsen, PhD8; Anne Watkins, BS1; Cecile Viboud, PhD2 Author Affiliations Article Information JAMA Intern Med. Published online July 1, 2020. doi:10.1001/jamainternmed.2020.3391 https://sci-hub.tw/10.1001/jamainternmed.2020.3391 Key Points Question Did more all-cause deaths occur during the first months of the coronavirus disease 2019 (COVID-19) pandemic in the United States compared with the same months during previous years? Findings In this cohort study, the number of deaths due to any cause increased by approximately 122 000 from March 1 to May 30, 2020, which is 28% higher than the reported number of COVID-19 deaths. Meaning Official tallies of deaths due to COVID-19 underestimate the full increase in deaths associated with the pandemic in many states. Abstract Importance Efforts to track the severity and public health impact of coronavirus disease 2019 (COVID-19) in the United States have been hampered by state-level differences in diagnostic test availability, differing strategies for prioritization of individuals for testing, and delays between testing and reporting. Evaluating unexplained increases in deaths due to all causes or attributed to nonspecific outcomes, such as pneumonia and influenza, can provide a more complete picture of the burden of COVID-19. Objective To estimate the burden of all deaths related to COVID-19 in the United States from March to May 2020. Design, Setting, and Population This observational study evaluated the numbers of US deaths from any cause and deaths from pneumonia, influenza, and/or COVID-19 from March 1 through May 30, 2020, using public data of the entire US population from the National Center for Health Statistics (NCHS). These numbers were compared with those from the same period of previous years. All data analyzed were accessed on June 12, 2020. Main Outcomes and Measures Increases in weekly deaths due to any cause or deaths due to pneumonia/influenza/COVID-19 above a baseline, which was adjusted for time of year, influenza activity, and reporting delays. These estimates were compared with reported deaths attributed to COVID-19 and with testing data. Results There were approximately 781 000 total deaths in the United States from March 1 to May 30, 2020, representing 122 300 (95% prediction interval, 116 800-127 000) more deaths than would typically be expected at that time of year. There were 95 235 reported deaths officially attributed to COVID-19 from March 1 to May 30, 2020. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19–reported deaths during that period. In several states, these deaths occurred before increases in the availability of COVID-19 diagnostic tests and were not counted in official COVID-19 death records. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths. Conclusions and Relevance Excess deaths provide an estimate of the full COVID-19 burden and indicate that official tallies likely undercount deaths due to the virus. The mortality burden and the completeness of the tallies vary markedly between states. Excess Deaths From COVID-19 and Other Causes, March-April 2020 Steven H. Woolf, MD, MPH1; Derek A. Chapman, PhD1; Roy T. Sabo, PhD2; et alDaniel M. Weinberger, PhD3; Latoya Hill, MPH1 Author Affiliations Article Information JAMA. Published online July 1, 2020. doi:10.1001/jama.2020.11787 https://jamanetwork.com/journals/jama/fullarticle/2768086?guestAccessKey=a41c1ad0-ef8f-41aa-b478-e3eff3f1e566&utm_source=silverchair&utm_campaign=jama_network&utm_content=covid_weekly_highlights&utm_medium=email https://sci-hub.tw/10.1001/jama.2020.11787
  6. Glycemic index, glycemic load, and risk of coronary heart disease: a pan-European cohort study. Sieri S, Agnoli C, Grioni S, Weiderpass E, Mattiello A, Sluijs I, Sanchez MJ, Jakobsen MU, Sweeting M, van der Schouw YT, Nilsson LM, Wennberg P, Katzke VA, Kühn T, Overvad K, Tong TYN, Conchi MI, Quirós JR, García-Torrecillas JM, Mokoroa O, Gómez JH, Tjønneland A, Sonestedt E, Trichopoulou A, Karakatsani A, Valanou E, Boer JMA, Verschuren WMM, Boutron-Ruault MC, Fagherazzi G, Madika AL, Bergmann MM, Schulze MB, Ferrari P, Freisling H, Lennon H, Sacerdote C, Masala G, Tumino R, Riboli E, Wareham NJ, Danesh J, Forouhi NG, Butterworth AS, Krogh V. Am J Clin Nutr. 2020 Jul 3:nqaa157. doi: 10.1093/ajcn/nqaa157. Online ahead of print. PMID: 32619242 Abstract Background: High carbohydrate intake raises blood triglycerides, glucose, and insulin; reduces HDLs; and may increase risk of coronary heart disease (CHD). Epidemiological studies indicate that high dietary glycemic index (GI) and glycemic load (GL) are associated with increased CHD risk. Objectives: The aim of this study was to determine whether dietary GI, GL, and available carbohydrates are associated with CHD risk in both sexes. Methods: This large prospective study-the European Prospective Investigation into Cancer and Nutrition-consisted of 338,325 participants who completed a dietary questionnaire. HRs with 95% CIs for a CHD event, in relation to intake of GI, GL, and carbohydrates, were estimated using covariate-adjusted Cox proportional hazard models. Results: After 12.8 y (median), 6378 participants had experienced a CHD event. High GL was associated with greater CHD risk [HR 1.16 (95% CI: 1.02, 1.31) highest vs. lowest quintile, p-trend 0.035; HR 1.18 (95% CI: 1.07, 1.29) per 50 g/day of GL intake]. The association between GL and CHD risk was evident in subjects with BMI (in kg/m2) ≥25 [HR: 1.22 (95% CI: 1.11, 1.35) per 50 g/d] but not in those with BMI <25 [HR: 1.09 (95% CI: 0.98, 1.22) per 50 g/d) (P-interaction = 0.022). The GL-CHD association did not differ between men [HR: 1.19 (95% CI: 1.08, 1.30) per 50 g/d] and women [HR: 1.22 (95% CI: 1.07, 1.40) per 50 g/d] (test for interaction not significant). GI was associated with CHD risk only in the continuous model [HR: 1.04 (95% CI: 1.00, 1.08) per 5 units/d]. High available carbohydrate was associated with greater CHD risk [HR: 1.11 (95% CI: 1.03, 1.18) per 50 g/d]. High sugar intake was associated with greater CHD risk [HR: 1.09 (95% CI: 1.02, 1.17) per 50 g/d]. Conclusions: This large pan-European study provides robust additional support for the hypothesis that a diet that induces a high glucose response is associated with greater CHD risk. Keywords: EPIC study; EPIC-CVD study; cohort study; coronary heart disease; glycemic index; glycemic load. Whole grain and dietary fiber intake and risk of colorectal cancer in the NIH-AARP Diet and Health Study cohort. Hullings AG, Sinha R, Liao LM, Freedman ND, Graubard BI, Loftfield E. Am J Clin Nutr. 2020 Jul 3:nqaa161. doi: 10.1093/ajcn/nqaa161. Online ahead of print. PMID: 32619213 Abstract Background: Whole grains and other foods containing fiber are thought to be inversely related to colorectal cancer (CRC). However, whether these associations reflect fiber or fiber source remains unclear. Objectives: We evaluated associations of whole grain and dietary fiber intake with CRC risk in the large NIH-AARP Diet and Health Study. Methods: We used Cox proportional hazard models to estimate HRs and 95% CIs for whole grain and dietary fiber intake and risk of CRC among 478,994 US adults, aged 50-71 y. Diet was assessed using a self-administered FFQ at baseline in 1995-1996, and 10,200 incident CRC cases occurred over 16 y and 6,464,527 person-years of follow-up. We used 24-h dietary recall data, collected on a subset of participants, to evaluate the impact of measurement error on risk estimates. Results: After multivariable adjustment for potential confounders, including folate, we observed an inverse association for intake of whole grains (HRQ5 vs.Q1 : 0.84; 95% CI: 0.79, 0.90; P-trend < 0.001), but not dietary fiber (HRQ5 vs. Q1: 0.96; 95% CI: 0.88, 1.04; P-trend = 0.40), with CRC incidence. Intake of whole grains was inversely associated with all CRC cancer subsites, particularly rectal cancer (HRQ5 vs. Q1: 0.76; 95% CI: 0.67, 0.87; P-trend < 0.001). Fiber from grains, but not other sources, was associated with lower incidence of CRC (HRQ5 vs. Q1: 0.89; 95% CI: 0.83, 0.96; P-trend < 0.001), particularly distal colon (HRQ5 vs. Q1: 0.84; 95% CI: 0.73, 0.96; P-trend = 0.005) and rectal cancer (HRQ5 vs. Q1: 0.77; 95% CI: 0.66, 0.88; P-trend < 0.001). Conclusions: Dietary guidance for CRC prevention should focus on intake of whole grains as a source of fiber. Keywords: colon cancer; colorectal cancer; diet; dietary fiber; epidemiology; rectal cancer; whole grains. Vitamin D status and risk of all-cause and cause-specific mortality in a large cohort: results from the UK Biobank. Fan X, Wang J, Song M, Giovannucci EL, Ma H, Jin G, Hu Z, Shen H, Hang D. J Clin Endocrinol Metab. 2020 Jul 4:dgaa432. doi: 10.1210/clinem/dgaa432. Online ahead of print. PMID: 32620963 https://sci-hub.tw/10.1210/clinem/dgaa432 Abstract Context: Although an inverse association between vitamin D status and mortality has been reported in observational studies, the precise association shape and optimal vitamin D status remain undetermined. Objective: To investigate the association between vitamin D status and risk of all-cause and cause-specific mortality, and estimate optimal serum 25-hydroxyvitamin D [25(OH)D] concentrations. Design: Prospective cohort study. Setting: UK Biobank. Participants: 365,530 participants who had serum 25(OH)D measurements and no history of cardiovascular disease (CVD), cancer, or diabetes at baseline (2006-2010). Main outcome measures: All-cause and cause-specific mortality. Results: During a median follow-up of 8.9 (interquartile range: 8.3-9.5) years, 10,175 deaths occurred, including 1841 (18.1%) due to CVD and 5737 (56.4%) due to cancer. The multivariate analyses revealed non-linear inverse associations, with a decrease in mortality risk appearing to level off at 60 nmol/L of 25(OH)D for all-cause and CVD deaths, and at 45 nmol/L for cancer deaths. Compared to participants with 25(OH)D concentrations below the cutoffs, those with higher concentrations had a 17% lower risk for all-cause mortality (HR: 0.83, 95% CI: 0.79-0.86), 23% lower risk for CVD mortality (HR: 0.77, 95% CI: 0.68-0.86), and 11% lower risk for cancer mortality (HR: 0.89, 95% CI: 0.84-0.95). Conclusions: Higher 25(OH)D concentrations are non-linearly associated with lower risk of all-cause, CVD, and cancer mortality. The thresholds of 45-60 nmol/L might represent an intervention target to reduce the overall risk of premature death, which needs further confirmation in large clinical trials. Keywords: 25-hydroxyvitamin D; cancer; cardiovascular disease; mortality; vitamin D. 24-h ambulatory blood pressure versus clinic blood pressure as predictors of cardiovascular risk: a systematic review and meta-analysis of prospective studies. Fan H, Onakpoya IJ, Heneghan CJ. J Hypertens. 2020 Jun 25. doi: 10.1097/HJH.0000000000002500. Online ahead of print. PMID: 32618886 Abstract Background: There is uncertainty about the usefulness of ambulatory blood pressure (ABP) in predicting cardiovascular disease (CVD) risk. Our objective was to compare the prognostic value of ABP versus clinic blood pressure (BP) in CVD. Methods: We conducted electronic searches on Medline, Embase, and the Cochrane library up to July 2018. We included prospective longitudinal studies that compared 24-h ABP with clinic BP measurement in adults. Our main outcomes were all-cause mortality, CVD mortality, and/or CVD events. We assessed study quality based on four domains and pooled data using a random effects model of STATA for meta-analyses. Results: We included 13 studies comprising 81 736 participants. The overall quality of the studies was moderate. Both systolic and diastolic 24-h ABP as well as systolic clinic BP significantly predicted all-cause mortality, CVD mortality, and CVD events. Systolic 24-h ABP was significantly better than systolic clinic BP at predicting future risk of CVD events: combined hazard ratio for 24-h ABP = 1.27 (95% confidence interval 1.21-1.34) per 10 mmHg increase in SBP compared with 1.13 (1.06-1.21) for clinic BP (interaction test P = 0.02). After adjusting for clinic BP, both systolic and diastolic 24-h ABP measurements were significantly better than their corresponding clinic measurements at predicting all-cause mortality, CVD mortality, and CVD events (P = 0.001 and P = 0.000, respectively). Conclusion: Systolic 24-h ABP is a better predictor of future CVD events than systolic clinic BP. Future studies should incorporate the use of individual patient data to assess the prognostic value of 24-h ABP. Association of Body Mass Index with the Risk of Incident Type 2 Diabetes, Cardiovascular Disease, and All-Cause Mortality: A Community-Based Prospective Study. Bae JC, Cho NH, Kim JH, Hur KY, Jin SM, Lee MK. Endocrinol Metab (Seoul). 2020 Jun;35(2):416-424. doi: 10.3803/EnM.2020.35.2.416. Epub 2020 Jun 24. PMID: 32615726 Abstract Background: Type 2 diabetes and cardiovascular disease (CVD) are the most important sequelae of obesity and the leading cause of death. We evaluated the association between body mass index (BMI) and the risk of incident type 2 diabetes, CVD, and all-cause mortality in a prospective study of a Korean population. Methods: The shapes of the associations were modeled by restricted cubic splines regression analysis. After categorizing all subjects (n=8,900) into octiles based on their BMI levels, we estimated the hazard ratio (HR) for the association of categorized BMI levels with the risk of incident CVD and type 2 diabetes using a Cox's proportional hazard analysis. Results: The mean age of participants was 52 years and 48% were men. Of the subjects at baseline, 39.0% of men and 45.6% of women were classified as obese (BMI ≥25 kg/m2). Over a mean follow-up of 8.1 years, CVD events occurred in 509 participants; 436 died; and 1,258 subjects developed type 2 diabetes. The increased risk of incident diabetes began to be significant at BMI 23 to 24 kg/m2 in both sexes (HR, 1.8). For CVD events, the risk began to increase significantly at BMI 26 to 28 kg/m2 (HR, 1.6). We found a reverse J-shaped relationship between BMI and all-cause mortality, with an increased risk among individuals with BMI values in lower range (BMI &lt;21 kg/m2). Conclusion: These results suggest that the BMI cut-off points for observed risk were varied depending on the diseases and that the BMI classification of obesity need to be revised to reflect differential risk of obesity-related diseases. Keywords: Cardiovascular diseases; Diabetes mellitus; Obesity; Body mass index. Dietary betaine intake is associated with skeletal muscle mass change over three years in middle-aged adults: the Guangzhou Nutrition and Health Study. Long JA, Zhong RH, Chen S, Wang F, Luo Y, Lu XT, Yishake D, Chen YM, Fang AP, Zhu HL. Br J Nutr. 2020 Jul 3:1-21. doi: 10.1017/S0007114520002433. Online ahead of print. PMID: 32616104 Abstract A higher dietary intake or serum concentration of betaine has been associated with greater lean body mass in middle-aged and older adults. However, it remains unknown whether betaine intake is associated with age-related loss of skeletal muscle mass (SMM). We assessed the association between dietary betaine intake and relative changes in SMM after 3 year in middle-aged adults. A total of 1242 participants aged 41-60 years from the Guangzhou Nutrition and Health Study (GNHS) 2011-2013 and 2014-2017 with body composition measurements by dual-energy x-ray absorptiometry were included. A face-to-face questionnaire was used to collect general baseline information. After adjustment for potential confounders, multiple linear regression found that energy-adjusted dietary betaine intake was significantly and positively associated with relative changes (i.e., percentage loss or increase) in SMM of legs, limbs, and appendicular skeletal mass index (ASMI) over 3-year follow-up [β(SE): 0.322 (0.157), 0.309 (0.142), and 0.303 (0.145), respectively; P < 0.05]. The ANCOVA models revealed that participants in the highest betaine tertile had significantly less loss in SMM of limbs and ASMI and more increase in SMM of legs over 3 years of follow-up, compared with those in the bottom betaine tertile (all P-trend < 0.05). In conclusion, our findings suggest that elevated higher dietary betaine intake may be associated with less loss of SMM of legs, limbs and ASMI in middle-aged adults. Keywords: dietary betaine; longitudinal change; prospective cohort study; skeletal muscle index; skeletal muscle mass. Dietary and circulating fatty acids and ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Yammine S, Huybrechts I, Biessy C, Dossus L, Aglago EK, Naudin S, Ferrari P, Weiderpass E, Tjonneland A, Hansen L, Overvad K, Romana Mancini F, Boutron-Ruault MC, Kvaskoff M, Fortner RT, Kaaks R, Schulze MB, Boing H, Trichopoulou A, Karakatsani A, La Vecchia C, Benetou V, Masala G, Krogh V, Mattiello A, Macciotta A, Gram IT, Skeie G, Quiros Garcia JR, Agudo A, Sanchez-Perez MJ, Chirlaque MD, Ardanaz E, Gil L, Sartor H, Drake I, Idahl A, Lundin EA, Aune D, Ward HA, Merritt MA, Allen NE, Gunter MJ, Chajes V. Cancer Epidemiol Biomarkers Prev. 2020 Jul 2:cebp.1477.2019. doi: 10.1158/1055-9965.EPI-19-1477. Online ahead of print. PMID: 32616494 Abstract Background: Fatty acids impact obesity, estrogens and inflammation, risk factors for ovarian cancer. Few epidemiological studies have investigated the association of fatty acids with ovarian cancer. Methods: Within the European Prospective Investigation into Cancer and nutrition, 1,486 incident ovarian cancer cases were identified. Cox Proportional Hazard models with adjustment for ovarian cancer risk factors were used to estimate hazard ratios of ovarian cancer across quintiles of intake of fatty acids. False discovery rate was computed to control for multiple testing. Multivariable conditional logistic regression models were used to estimate odds ratios of ovarian cancer across tertiles of plasma fatty acids among 633 cases and two matched controls in a nested case-control analysis. Results: A positive association was found between ovarian cancer and intake of industrial trans elaidic acid (Hazard Ratio comparing 5th with 1st quintileQ5-Q1=1.29; 95% CI=1.03-1.62; ptrend=0.02, q-value=0.06). Dietary intakes of n-6 linoleic acid (HRQ5-Q1=1.10; 95% CI=1.01-1.21; ptrend=0.03) and n-3 α-linolenic acid (HRQ5-Q1=1.18; 95% CI=1.05-1.34; ptrend=0.007) from deep frying fats were also positively associated with ovarian cancer. Suggestive associations were reported for circulating elaidic (Odds Ratio comparing 3rd with 1st tertileT3-T1 = 1.39; 95% CI=0.99-1.94; ptrend=0.06) and α-linolenic acids (ORT3-T1=1.30; 95% CI=0.98-1.72; ptrend=0.06). Conclusions: Our results suggest that higher intakes and circulating levels of industrial trans elaidic acid, and higher intakes of linoleic acid and α-linolenic acid from deep frying fat, may be associated with greater risk of ovarian cancer. Impact: If causal, eliminating industrial trans fatty acids could offer a straightforward public health action for reducing ovarian cancer.
  7. The Performance Effect of Scheduled Carbohydrate and Caffeine Intake during Simulated Team Sport Match-Play. Keane J, Shovlin A, Devenney S, Malone S, Young D, Coratella G, Collins K, Shortall M. Nutrients. 2020 Jun 29;12(7):E1926. doi: 10.3390/nu12071926. PMID: 32610573 Abstract The aim of the current investigation was to identify the effects of scheduled carbohydrate (CHO) and caffeine (CAF) supplementation on simulated team sport match-play performance. Ten male hurling players completed three hurling match-play simulation protocols (HSP) performed 7 days apart in a double-blind, randomized design. Supplementation included CHO, CHO + CAF, and placebo (PLA). In a randomized order, participants ingested either a 6% CHO solution, a PLA solution of similar taste, or a combined intake of 6% CHO solution + 200 mg CAF capsule. At specific time points (Pre-0 min; half time (HT)-30 min; full time (FT)-60 min), participants completed a repeated sprint protocol (RAST; 12 × 20 m). Physiological [% maximal oxygen uptake (%VO2max), % mean oxygen uptake (%VO2mean), % maximal heart rate (%HRmax), % mean heart rate (%HRmean), respiratory exchange ratio (RER), and blood lactate (BLa)] and performance [(best sprint time (RSAbest), mean sprint time (RSAmean), and rate of perceived exertion (RPE)] variables were monitored throughout each simulation. Non-significant differences were observed between supplement trials (CHO, CHO + CAF, and PLA) for BLa (η2 = 0.001, small), %VO2max (η2 = 0.001, small), %VO2mean (η2 = 0.004, small), %HRmax (η2 = 0.007, small), %HRmean (η2 = 0.018, small), RER (η2 = 0.007, small), RPE (η2 = 0.007, small), and RSAbest (η2 = 0.050, small). RSAmean performance significantly improved in CHO + CAF trials compared to PLA, with sprint times significantly improved from Pre to FT also (η2 = 0.135, medium). A significant difference was observed in BLa between time points (Pre, HT, and FT) (η2 = 0.884, large) in % HRmax (η2 = 0.202, medium), %HRmean (η2 = 0.477, large), and RER (η2 = 0.554, large) across halves and in RPE across time points (η2 = 0.670, large). Our data provide novel data regarding the effects of CHO and CAF supplementation on team sport performance, with co-ingestion of CHO + CAF reducing the decrement in repeated sprint performance compared to PLA. Keywords: aerobic performance; ergogenic aids; internal load; repeated sprint-ability; team sports. Caffeine-Containing, Adaptogenic-Rich Drink Modulates the Effects of Caffeine on Mental Performance and Cognitive Parameters: A Double-Blinded, Placebo-Controlled, Randomized Trial. Boolani A, Fuller DT, Mondal S, Wilkinson T, Darie CC, Gumpricht E. Nutrients. 2020 Jun 29;12(7):E1922. doi: 10.3390/nu12071922. PMID: 32610481 Abstract Using a placebo-controlled, double-blinded, within-participants, randomized, cross-over design, we examined the neurocognitive effects of a: (a) caffeine-containing, adaptogenic herbal-rich natural energy shot (e+ shot), (b) a matched caffeine-containing shot (caffeine), and, (c) a placebo. Participants (n = 30) were low consumers of caffeine without elevated feelings of energy. Before and three times after beverage consumption, a 27-min battery was used to assess motivation to perform cognitive tasks, mood, attention ((serial subtractions of 3 (SS3) and 7 (SS7), the continuous performance task (CPT), and the rapid visual input processing tasks)), heart rate (HR), blood pressure (BP), and motor coordination (nine-hole peg test) with a 10-min break between each post-consumption battery. The procedure was repeated for each beverage for each participant at least 48 h apart and within 30 min the same time of day using a random group assignment with blinding of researchers and subjects. To evaluate for changes in outcomes, a Treatment × Time analysis of covariance controlling for hours of prior night's sleep was used. Analysis of all outcomes and all treatment comparisons indicated that compared to placebo, both e+ shot ( Δ ¯ &nbsp; = 2.60; η2 = 0.098) and caffeine ( Δ ¯ &nbsp; = 5.30, η2 = 0.098) increased systolic BP 30 min post consumption (still within normal healthy ranges). The caffeine beverage also led to an improvement in most cognitive measures and moods 30-min post-consumption with improvements tapering at 69 and 108 min, while e+ shot noted more steady improvements with no significant differences between beverages on most cognitive and mood measures at 69 and 108 min. However, compared to caffeine, e+ shot noted a significant increase in reaction time at 108 min, while caffeine noted a small change in the opposite direction. No side-effects were reported by any intervention. These results suggest that the specific blend of adaptogens in e+ shot may modulate the neurocognitive effects of caffeine on mood, and cognition. Keywords: adaptogens; caffeine; cognition; energy; fatigue; mood. The Influence of Different Foods and Food Ingredients on Acute Postprandial Triglyceride Response: A Systematic Literature Review and Meta-Analysis of Randomized Controlled Trials. Lee DPS, Low JHM, Chen JR, Zimmermann D, Actis-Goretta L, Kim JE. Adv Nutr. 2020 Jul 1:nmaa074. doi: 10.1093/advances/nmaa074. Online ahead of print. PMID: 32609800 Abstract The use of postprandial triglyceride (ppTG) as a cardiovascular disease risk indicator has gained recent popularity. However, the influence of different foods or food ingredients on the ppTG response has not been comprehensively characterized. A systematic literature review and meta-analysis was conducted to assess the effects of foods or food ingredients on the ppTG response. PubMed, MEDLINE, Cochrane, and CINAHL databases were searched for relevant acute (<24-h) randomized controlled trials published up to September 2018. Based on our selection criteria, 179 relevant trials (366 comparisons) were identified and systematically compiled into distinct food or food ingredient categories. A ppTG-lowering effect was noted for soluble fiber (Hedges' giAUC = -0.72; 95% CI: -1.33, -0.11), sodium bicarbonate mineral water (Hedges' gAUC = -0.42; 95% CI: -0.79, -0.04), diacylglycerol oil (Hedges' giAUC = -0.38; 95% CI: -0.75, -0.00), and whey protein when it was contrasted with other proteins. The fats group showed significant but opposite effects depending on the outcome measure used (Hedges' giAUC = -0.32; 95% CI: -0.61, -0.03; and Hedges' gAUC = 0.16; 95% CI: 0.06, 0.26). Data for other important food groups (nuts, vegetables, and polyphenols) were also assessed but of limited availability. Assessing for oral fat tolerance test (OFTT) recommendation compliance, most trials were ≥4 h long but lacked a sufficiently high fat challenge. iAUC and AUC were more common measures of ppTG. Overall, our analyses indicate that the effects on ppTG by different food groups are diverse, largely influenced by the type of food or food ingredient within the same group. The type of ppTG measurement can also influence the response. Keywords: food; ingredient; lipemia; oral fat tolerance test recommendation; postprandial; triglyceride; triglyceridemia. Lifespan-extending interventions enhance lipid-supported mitochondrial respiration in Caenorhabditis elegans. Macedo F, Romanatto T, Gomes de Assis C, Buis A, Kowaltowski AJ, Aguilaniu H, Marques da Cunha F. FASEB J. 2020 Jul 1. doi: 10.1096/fj.201901880R. Online ahead of print. PMID: 32609395 Abstract Dietary restriction and reduced reproduction have been linked to long lifespans in the vast majority of species tested. Although decreased mitochondrial mass and/or function are hallmarks of aging, little is known about the mechanisms by which these organelles contribute to physiological aging or to the effects of lifespan-extending interventions, particularly with respect to oxidative phosphorylation and energy production. Here, we employed the nematode Caenorhabditis elegans to examine the effects of inhibition of germline proliferation and dietary restriction, both of which extend the lifespan of C. elegans, on mitochondrial respiratory activity in whole animals and isolated organelles. We found that oxygen consumption rates and mitochondrial mass were reduced in wild-type (WT) C. elegans subjected to bacterial deprivation (BD) compared with animals fed ad libitum (AL). In contrast, BD decreased the rate of oxygen uptake but not mitochondrial mass in germline-less glp-1(e2144ts) mutants. Interestingly, mitochondria isolated from animals subjected to BD and/or inhibition of germline proliferation showed no differences in complex I-mediated respiratory activity compared to control mitochondria, whereas both interventions enhanced the efficiency with which mitochondria utilized lipids as respiratory substrates. Notably, the combination of BD and inhibition of germline proliferation further increased mitochondrial lipid oxidation compared to either intervention alone. We also detected a striking correlation between lifespan extension in response to BD and/or inhibition of germline proliferation and the capacity of C. elegans to generate ATP from lipids. Our results thus suggest that the ability to oxidize lipids may be determinant in enhanced longevity. Keywords: C. elegans; dietary restriction; lipid oxidation; longevity; mitochondrial metabolism. Dietary Factors and Risk of Chronic Obstructive Pulmonary Disease: a Systemic Review and Meta-Analysis. Seyedrezazadeh E, Moghaddam MP, Ansarin K, Asghari Jafarabadi M, Sharifi A, Sharma S, Kolahdooz F. Tanaffos. 2019 Apr;18(4):294-309. PMID: 32607110 Free PMC article. Review. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309892/pdf/Tanaffos-18-294.pdf Abstract Background: The relationship between dietary pattern and the risk of chronic obstructive pulmonary disease (COPD) has been described; however, the exclusive role of dietary factors remains controversial. Hence, we conducted this systematic meta-analysis to clarify the role of some nutrients and antioxidant vitamins in the risk of COPD. Materials and methods: PubMed, Embase, and Scopus databases were searched for studies evaluating the associations between COPD outcome measures, symptoms, and mortality, and intake of fruits and vegetables, fiber, fish, n-3 or n-6 fatty acids, and antioxidant vitamins in adults. The random-effect model meta-analyses were used to pool the results. Results: Ten cohort, six case-control, and 20 cross-sectional studies were identified. The pooled relative risks (RRs) of the COPD and confidence intervals (CIs) for the highest intake group compared with the lowest intake group were 0.74 (95% CI: 0.65-0.85) for fruit, 0.65 (95% CI: 0.55-0.78) for dietary fiber, 0.71 (95% CI: 0.58-0.85) for fish, and 0.89 (95% CI: 0.76-0.99) for vitamin C. No association was observed between the risk of COPD and the intake of vegetables, n-3 fatty acids, vitamin E, and β-carotene; however, it was associated with n-6 fatty acids 1.06 (95% CI: 0.87-1.30). Conclusion: The results suggested that a higher intake of fruits, probably dietary fiber, and fish reduce the risk of COPD. Keywords: Antioxidant Vitamins; COPD; Dietary Fiber; Fatty Acids; Fruit; Vegetables. Clinical determinants of low handgrip strength and its decline in the oldest old: the Leiden 85-plus Study. Ling CHY, Gussekloo J, Trompet S, Meskers CGM, Maier AB. Aging Clin Exp Res. 2020 Jun 30. doi: 10.1007/s40520-020-01639-4. Online ahead of print. PMID: 32607865 Abstract Background: Age-related decline in muscle strength, dynapenia, is linked to serious adverse health outcomes. Evidence on the determinants of muscle strength decline in the oldest old is lacking. Aims: To identify clinical variables associated with handgrip strength and its change over a 4-year period in an oldest old cohort. Methods: We included 555 participants from the Leiden 85-plus Study, a prospective population-based study of 85-year-old inhabitants of Leiden, the Netherlands. Handgrip strength was assessed at age 85 and 89 years. Anthropometry, mental status, functional performance, and biochemical variables were obtained at baselines. Significant univariates were included into multivariable regression models to extract the final predictive variables. Results: Handgrip strength for men and women at age 85 years was 30.6 kg (SD 8.2) and 18.7 kg (SD, 5.5), respectively. In the cross-sectional analysis, body height and weight were positively associated with handgrip strength in both genders. Higher functional performance was associated with stronger handgrip strength in women. Mean absolute handgrip strength decline over 4 years was greater for men than women (- 6.1 kg (SD, 5.2) vs. - 3.4 kg (SD, 4.1), p < 0.001). Men with better baseline cognitive functioning had smaller decline in handgrip strength. Conclusions: This study further strengthens evidence linking functional and cognitive performances to muscle strength in the oldest old. Future research is needed to ascertain causality and determine if these markers represent potential targets for intervention. Keywords: Cognitive function; Muscle strength; Physical fitness; Sex differences. Dietary Methionine Restriction Ameliorated Fat Accumulation, Systemic Inflammation, and Increased Energy Metabolism by Altering Gut Microbiota in Middle-aged Mice Administered Different Fat Diets. Wu G, Shi Y, Han L, Feng C, Ge Y, Yu Y, Tang X, Cheng X, Sun J, Le GW. J Agric Food Chem. 2020 Jun 27. doi: 10.1021/acs.jafc.0c02965. Online ahead of print. PMID: 32597175 Abstract Diet greatly influences gut microbiota. Dietary methionine restriction (MR) prevents and ameliorates age-related or high-fat induced diseases, and prolongs life-span. This study aimed to reveal the impact of MR on gut microbiota in middle-aged mice with low-, medium-, high-fat diets. C57BL/6J mice were randomly divided into six groups with different MR and fat-content diets. Multiple indicators of intestinal function, fat accumulation, energy consumption, and inflammation were measured. 16S rRNA gene sequencing was used to analyze cecal microbiota. Our results indicated that MR considerably dropped the concentrations of lipopolysaccharides (LPS) and increased short-chain fatty acids (SCFAs) by upregulating the abundance of Corynebacterium and SCFAs-producing bacterium Bacteroides, Faecalibaculum, Roseburia, and downregulating the LPS-producing or pro-inflammatory bacterium Desulfovibrio and Escherichia-Shigella. These variations upon MR irrespective of fat content contributed to reducing fat accumulation, systemic inflammation, heat production, and strengthening the intestinal mucosal immunity barrier by LPS/LBP/CD14/TLR4 signal pathway in middle-aged mice. Omega-3 Fatty Acid Supplements for the Prevention of Cardiovascular Disease. Lan M, Nguyen T, Gray S. Sr Care Pharm. 2020 Jul 1;35(7):318-323. doi: 10.4140/TCP.n.2020.318.. PMID: 32600510 Abstract In the United States, cardiovascular disease (CVD) is the most common cause of death in older people. The use of omega-3 fatty acid supplements (nonprescription) is common in older people, despite the conflicting evidence regarding the benefits of supplements in CVD. The 2017 American Heart Association science advisory on omega-3 fatty acid supplements suggested that it is reasonable to use omega-3 fatty acids for secondary prevention in people with coronary heart disease and heart failure. This article reviewed large meta-analyses and clinical trials published since the science advisory. Two metaanalyses concluded that these supplements were not effective for secondary or primary prevention of CVD. Two large randomized, placebo-controlled clinical trials, one in people with diabetes mellitus, evaluated omega-3 fatty acid supplements for primary prevention and reported no benefit. Taken together, these findings do not support the routine dietary supplementation with omega-3 fatty acids to prevent cardiovascular events.
  8. AlPater

    Al's CR updates

    Sex-Specific Response to Caloric Restriction After Reproductive Investment in Microcebus murinus: An Integrative Approach. Noiret A, Puch L, Riffaud C, Costantini D, Riou JF, Aujard F, Terrien J. Front Physiol. 2020 Jun 16;11:506. doi: 10.3389/fphys.2020.00506. eCollection 2020. PMID: 32612534 Free PMC article Abstract In seasonal environments, males and females usually maintain high metabolic activity during the whole summer season, exhausting their energy reserves. In the global warming context, unpredictability of food availability during summer could dramatically challenge the energy budget of individuals. Therefore, one can predict that resilience to environmental stress would be dramatically endangered during summer. Here, we hypothesized that females could have greater capacity to survive harsh conditions than males, considering the temporal shift in their respective reproductive energy investment, which can challenge them differently, as well as enhanced flexibility in females' physiological regulation. We tackled this question on the gray mouse lemur (Microcebus murinus), focusing on the late summer period, after the reproductive effort. We monitored six males and six females before and after a 2-weeks 60% caloric restriction (CR), measuring different physiological and cellular parameters in an integrative and comparative multiscale approach. Before CR, females were heavier than males and mostly characterized by high levels of energy expenditure, a more energetic mitochondrial profile and a downregulation of blood antioxidants. We observed a similar energy balance between sexes due to CR, with a decrease in metabolic activity over time only in males. Oxidative damage to DNA was also reduced by different pathways between sexes, which may reflect variability in their physiological status and life-history traits at the end of summer. Finally, females' mitochondria seemed to exhibit greater flexibility and greater metabolic potential than males in response to CR. Our results showed strong differences between males and females in response to food shortage during late summer, underlining the necessity to consider sex as a factor for population dynamics in climate change models. Keywords: caloric restriction; non-human primate; oxidative stress; reproductive investment; season; sex.
  9. There was also this report: https://www.cbc.ca/news/politics/coronavirus-pandemic-military-long-term-care-quebec-1.5629067
  10. Body mass index, waist circumference, and risk of hearing loss: a meta-analysis and systematic review of observational study. Yang JR, Hidayat K, Chen CL, Li YH, Xu JY, Qin LQ. Environ Health Prev Med. 2020 Jun 26;25(1):25. doi: 10.1186/s12199-020-00862-9. PMID: 32590951 Review. Abstract Background: Emerging evidence implicates excess weight as a potential risk factor for hearing loss. However, this association remained inconclusive. Therefore, we aimed to systematically and quantitatively review the published observational study on the association between body mass index (BMI) or waist circumference (WC) and hearing loss. Methods: The odds ratios (ORs) or relative risks (RRs) with their 95% confidence intervals (CIs) were pooled under a random-effects model. Fourteen observational studies were eligible for the inclusion in the final analysis. Results: In the meta-analysis of cross-sectional studies, the ORs for prevalent hearing loss were 1.10 (95% CI 0.88, 1.38) underweight, 1.14 (95% CI 0.99, 1.32) for overweight, OR 1.40 (95% CI 1.14, 1.72) for obesity, 1.14 (95% CI 1.04, 1.24) for each 5 kg/m2 increase in BMI, and 1.22 (95% CO 0.88. 1.68) for higher WC. In the meta-analysis of longitudinal studies, the RRs were 0.96 (95% CI 0.52, 1.79) for underweight, 1.15 (95% CI 1.04, 1.27) for overweight, 1.38 (95% CI 1.07, 1.79) for obesity, 1.15 (95% CI 1.01, 1.30) for each 5 kg/m2 increase in BMI, and 1.11 (95% CI 1.01, 1.22) for higher WC. Conclusions: In summary, our findings add weight to the evidence that elevated BMI and higher WC may be positively associated with the risk of hearing loss. Keywords: Adiposity; Body mass index; Hearing loss; Obesity; Overweight; Waist circumference. In-Hospital Use of Statins Is Associated with a Reduced Risk of Mortality among Individuals with COVID-19. Zhang XJ, Qin JJ, Cheng X, Shen L, Zhao YC, Yuan Y, Lei F, Chen MM, Yang H, Bai L, Song X, Lin L, Xia M, Zhou F, Zhou J, She ZG, Zhu L, Ma X, Xu Q, Ye P, Chen G, Liu L, Mao W, Yan Y, Xiao B, Lu Z, Peng G, Liu M, Yang J, Yang L, Zhang C, Lu H, Xia X, Wang D, Liao X, Wei X, Zhang BH, Zhang X, Yang J, Zhao GN, Zhang P, Liu PP, Loomba R, Ji YX, Xia J, Wang Y, Cai J, Guo J, Li H. Cell Metab. 2020 Jun 24:S1550-4131(20)30316-8. doi: 10.1016/j.cmet.2020.06.015. Online ahead of print. PMID: 32592657 Abstract Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression. Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins. Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58. The statin use-associated lower risk of mortality was also observed in the Cox time-varying model and marginal structural model analysis. These results give support for the completion of ongoing prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic. Keywords: ACEi/ARB; COVID-19; SARS-COV-2; mortality; statin. An Insulin-Sensitive Circular RNA that Regulates Lifespan in Drosophila. Weigelt CM, Sehgal R, Tain LS, Cheng J, Eßer J, Pahl A, Dieterich C, Grönke S, Partridge L. Mol Cell. 2020 Jun 19:S1097-2765(20)30396-8. doi: 10.1016/j.molcel.2020.06.011. Online ahead of print. PMID: 32592682 Abstract Circular RNAs (circRNAs) are abundant and accumulate with age in neurons of diverse species. However, only few circRNAs have been functionally characterized, and their role during aging has not been addressed. Here, we use transcriptome profiling during aging and find that accumulation of circRNAs is slowed down in long-lived insulin mutant flies. Next, we characterize the in vivo function of a circRNA generated by the sulfateless gene (circSfl), which is consistently upregulated, particularly in the brain and muscle, of diverse long-lived insulin mutants. Strikingly, lifespan extension of insulin mutants is dependent on circSfl, and overexpression of circSfl alone is sufficient to extend the lifespan. Moreover, circSfl is translated into a protein that shares the N terminus and potentially some functions with the full-length Sfl protein encoded by the host gene. Our study demonstrates that insulin signaling affects global circRNA accumulation and reveals an important role of circSfl during aging in vivo. Keywords: Drosophila; ageing; alternative splicing; backsplicing; circRNA; heparan sulfate; insulin; longevity; non-coding RNAs; sulfateless. Denosumab, raloxifene, romosozumab and teriparatide to prevent osteoporotic fragility fractures: a systematic review and economic evaluation. Davis S, Simpson E, Hamilton J, James MM, Rawdin A, Wong R, Goka E, Gittoes N, Selby P. Health Technol Assess. 2020 Jun;24(29):1-314. doi: 10.3310/hta24290. PMID: 32588816 Abstract Background: Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. Objectives: The objectives were to evaluate the clinical effectiveness, safety and cost-effectiveness of non-bisphosphonates {denosumab [Prolia®; Amgen Inc., Thousand Oaks, CA, USA], raloxifene [Evista®; Daiichi Sankyo Company, Ltd, Tokyo, Japan], romosozumab [Evenity®; Union Chimique Belge (UCB) S.A. (Brussels, Belgium) and Amgen Inc.] and teriparatide [Forsteo®; Eli Lilly and Company, Indianapolis, IN, USA]}, compared with each other, bisphosphonates or no treatment, for the prevention of fragility fracture. Data sources: For the clinical effectiveness review, nine electronic databases (including MEDLINE, EMBASE and the World Health Organization International Clinical Trials Registry Platform) were searched up to July 2018. Review methods: A systematic review and network meta-analysis of fracture and femoral neck bone mineral density were conducted. A review of published economic analyses was undertaken and a model previously used to evaluate bisphosphonates was adapted. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years for a simulated cohort of patients with heterogeneous characteristics. This was done for each non-bisphosphonate treatment, a strategy of no treatment, and the five bisphosphonate treatments previously evaluated. The model was populated with effectiveness evidence from the systematic review and network meta-analysis. All other parameters were estimated from published sources. An NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture® (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX® (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net monetary benefit was estimated using non-parametric regression. A probabilistic sensitivity analysis and scenario analyses were used to assess uncertainty. Results: Fifty-two randomised controlled trials of non-bisphosphonates were included in the clinical effectiveness systematic review and an additional 51 randomised controlled trials of bisphosphonates were included in the network meta-analysis. All treatments had beneficial effects compared with placebo for vertebral, non-vertebral and hip fractures, with hazard ratios varying from 0.23 to 0.94, depending on treatment and fracture type. The effects on vertebral fractures and the percentage change in bone mineral density were statistically significant for all treatments. The rate of serious adverse events varied across trials (0-33%), with most between-group differences not being statistically significant for comparisons with placebo/no active treatment, non-bisphosphonates or bisphosphonates. The incremental cost-effectiveness ratios were > £20,000 per quality-adjusted life-year for all non-bisphosphonate interventions compared with no treatment across the range of QFracture and FRAX scores expected in the population eligible for fracture risk assessment. The incremental cost-effectiveness ratio for denosumab may fall below £30,000 per quality-adjusted life-year at very high levels of risk or for high-risk patients with specific characteristics. Raloxifene was dominated by no treatment (resulted in fewer quality-adjusted life-years) in most risk categories. Limitations: The incremental cost-effectiveness ratios are uncertain for very high-risk patients. Conclusions: Non-bisphosphonates are effective in preventing fragility fractures, but the incremental cost-effectiveness ratios are generally greater than the commonly applied threshold of £20,000-30,000 per quality-adjusted life-year. Keywords: ECONOMIC EVALUATION; FRAGILITY FRACTURE; NETWORK META-ANALYSIS; NON-BISPHOSPHONATE; OSTEOPOROSIS; SYSTEMATIC REVIEW. Effect of glucose and sucrose on cognition in healthy humans: a systematic review and meta-analysis of interventional studies. García CR, Piernas C, Martínez-Rodríguez A, Hernández-Morante JJ. Nutr Rev. 2020 Jun 25:nuaa036. doi: 10.1093/nutrit/nuaa036. Online ahead of print. PMID: 32585003 Abstract Context: Evidence suggests that plasma glucose levels may influence cognitive performance, but this has not been systematically reviewed and quantified. Objective: The aim of this review was to investigate the potential effects of glucose and sucrose, compared with placebo, on cognition in healthy humans. Data sources: The electronic databases PubMed and Web of Science were searched up to December 2019. Reference lists of selected articles were checked manually. Study selection: Randomized controlled trials or crossover trials that compared glucose or sucrose with placebo for effects on cognition were eligible. Data extraction: Potentially eligible articles were selected independently by 2 authors. Risk of bias was assessed through the Cochrane Collaboration tool. Standardized mean differences (SMDs) were obtained from random-effects meta-analyses for a subsample of studies that reported the same outcomes. Results: Thirty-seven trials were identified, of which 35 investigated the effect of glucose consumption compared with placebo on cognition. Two studies found no effect of glucose on cognition, while the others found mixed results. Only 3 of the 37 studies investigated the effects of sucrose intake, reporting mixed results. Meta-analyses revealed a significantly positive effect of glucose compared with control, but only when a verbal performance test (immediate word recall) was used in parallel-design studies (SMD = 0.61; 95%CI, 0.20-1.02; I2 = 0%). Twenty-four studies were classified as having high risk of bias for the selection procedure. Conclusions: A limited body of evidence shows a beneficial effect of glucose in individuals performing immediate verbal tasks. High-quality trials with standardized cognitive measurements are needed to better establish the effect of glucose or sucrose on cognition. Keywords: cognition; executive functions; glucose; sucrose; sugar. Whole milk consumption is associated with lower risk of coronary artery calcification progression: evidences from the Multi-Ethnic Study of Atherosclerosis. Ghosh S, He W, Gao J, Luo D, Wang J, Chen J, Huang H. Eur J Nutr. 2020 Jun 24. doi: 10.1007/s00394-020-02301-5. Online ahead of print. PMID: 32583016 Abstract Purpose: Coronary artery calcification (CAC) progression is a strong predictor of cardiovascular disease (CVD) morbidity and mortality. However, the association between whole milk and CAC progression remains unknown. Recent studies highlighted beneficial effects of short chain fatty acids (SCFA) from whole milk on CVD. In this study, we attempted to investigate the relationship between whole milk consumption and CAC progression, and the potential effect of SCFA in it. Methods: We analyzed a population-based cohort with 5273 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who completed a dietary questionnaire at baseline. CAC was measured at baseline and subsequent follow-up examinations by multi-detector computed tomography (MDCT) scans with Agatston scores. CAC progression was defined as increased CAC scores in the follow-up from the baseline exam. Results: Participants consuming whole milk exhibited lower baseline CAC and CAC progression than those who never/rarely consumed whole milk (P < 0.001 and P = 0.010, respectively). Moreover, multivariable logistic regression analysis demonstrated that whole milk intake was independently associated with lower CAC progression (OR 0.765; 95% CI 0.600-0.977; P = 0.032), especially in males, participants with age ≤ 64 years and with body mass index (BMI) ≤ 25 kg/m2. Mediation analysis further showed that caproic acid, one kind of SCFA, partly mediated protective effects of whole milk on CAC progression. Conclusions: Self-reported whole milk consumption was inversely associated with CAC progression in community-dwelling participants, especially in those at relatively low cardiovascular risks. The beneficial effect was partially mediated by SCFA. Therefore, whole milk can be incorporated into part of a cardio-protective diet. Regarding this, future studies may target SCFA to provide insight into more mechanistic views. Keywords: Cardiovascular disease; Coronary artery calcification; Short chain fatty acids; Whole milk. The Effect of Caffeine on the Risk and Progression of Parkinson's Disease: A Meta-Analysis. Hong CT, Chan L, Bai CH. Nutrients. 2020 Jun 22;12(6):E1860. doi: 10.3390/nu12061860. PMID: 32580456 Abstract Coffee and caffeine are speculated to be associated with the reduced risk of Parkinson's disease (PD). The present study aimed to investigate the disease-modifying potential of caffeine on PD, either for healthy people or patients, through a meta-analysis. The electronic databases were searched using terms related to PD and coffee and caffeinated food products. Articles were included only upon fulfillment of clear diagnostic criteria for PD and details regarding their caffeine content. Reference lists of relevant articles were reviewed to identify eligible studies not shortlisted using these terms. In total, the present study enrolled 13 studies, nine were categorized into a healthy cohort and the rest into a PD cohort. The individuals in the healthy cohort with regular caffeine consumption had a significantly lower risk of PD during follow-up evaluation (hazard ratio (HR) = 0.797, 95% CI = 0.748-0.849, p < 0.001). The outcomes of disease progression in PD cohorts included dyskinesia, motor fluctuation, symptom onset, and levodopa initiation. Individuals consuming caffeine presented a significantly lower rate of PD progression (HR = 0.834, 95% CI = 0.707-0.984, p = 0.03). In conclusion, caffeine modified disease risk and progression in PD, among both healthy individuals or those with PD. Potential biological benefits, such as those obtained from adenosine 2A receptor antagonism, may require further investigation for designing new drugs. Keywords: Parkinson’s disease; caffeine; meta-analysis; progression; risk. Hypertension is associated with oral, laryngeal, and esophageal cancer: a nationwide population-based study. Seo JH, Kim YD, Park CS, Han KD, Joo YH. Sci Rep. 2020 Jun 24;10(1):10291. doi: 10.1038/s41598-020-67329-3. PMID: 32581314 Abstract Several studies have reported an association between hypertension and upper aerodigestive tract cancer, but no large-scale, population-based studies have been conducted to confirm this.The aim of this study was to explore the association between hypertension and risk of upper aerodigestive tract cancer in Koreans. Participants who underwent a national health screening examination from January 1 to December 31, 2009 (n = 9,746,606) were enrolled. We assessed the development of oral, laryngeal, or esophageal cancer until 2016 using records from the Korean Health Insurance claims database during the study period. During the seven-year follow-up period, 6,062, 2,658, and 4,752 subjects were newly diagnosed with oral, laryngeal, and esophageal cancer, respectively. Participants with metabolic syndrome had the highest risk of developing oral cancer (hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.03-1.16), laryngeal cancer (HR 1.27, 95% CI 1.17-1.38), and esophageal cancer (HR 1.11, 95% CI 1.04-1.19). Hypertension was a remarkable risk factor for each cancer (HR 1.11, 95% CI 1.04-1.17 for oral cancer; HR 1.23, 95% CI 1.13-1.33 for laryngeal cancer; HR 1.25, 95% CI 1.18-1.33 for esophageal cancer) after adjusting for age and other variables including gender, smoking status, alcohol intake, exercise, body mass index, and diabetes. Patients with untreated hypertension were at highest risk of developing oral cancer (HR 1.15; 95% CI 1.05-1.26), laryngeal cancer (HR 1.25; 95% CI 1.09-1.44), and esophageal cancer (HR 1.47; 95% CI 1.33-1.63) after adjusting for confounders. Hypertension was associated with the risk of oral, laryngeal, and esophageal cancer, despite of the lack of detailed biochemical information including the cancer cell types (squamous cell carcinoma or adenocarcinoma), cancer stage, physical findings and other medical history. Further studies are warranted to determine the reasons for this association and to establish effective interventions in this vulnerable population.
  11. A mushroom diet reduced the risk of pregnancy-induced hypertension and macrosomia: a randomized clinical trial. Sun L, Niu Z. Food Nutr Res. 2020 Jun 8;64. doi: 10.29219/fnr.v64.4451. eCollection 2020. PMID: 32577117 Free PMC article. Abstract Background: Pregnancy-induced hypertension (PIH) is a disease characterized by high blood pressure detected after 20 weeks of pregnancy, affecting approximately 10% of pregnant women worldwide. Effective strategies are imperatively needed to prevent and treat PIH. Methods: Subjects were required to consume 100 g mushroom daily from pre-pregnancy to the 20th week of gestation. The gestational hypertension and related primary and secondary outcomes of the mushroom diet (MD) group and placebo group were investigated to compare the intervention of a MD on the PIH and preeclampsia-associated maternal and child health conditions. Results: A total of 582 and 580 subjects belonging to the MD group and placebo group were included for the analysis, respectively. Compared to the placebo, the MD significantly reduced the incidence of gestational hypertension (P = 0.023), preeclampsia (P = 0.014), gestational weight gain (P = 0.017), excessive gestational weight gain (P = 0.032) and gestational diabetes (P = 0.047). Stratified analysis showed that the MD lowered the risk of PIH for overweighed women (P = 0.036), along with the percentage of macrosomia (P = 0.007). Conclusion: An MD could serve as a preventative strategy for lowering the risk of PIH and could control newborn birthweight while reducing comorbidities including gestational weight gain, diabetes etc. Keywords: clinical trial; mushroom; non-pharmacological intervention; preeclampsia; pregnancy-induced hypertension. Coffee consumption and risk of hypertension: A prospective analysis in the cohort study. Miranda AM, Goulart AC, Benseñor IM, Lotufo PA, Marchioni DM. Clin Nutr. 2020 Jun 7:S0261-5614(20)30289-2. doi: 10.1016/j.clnu.2020.05.052. Online ahead of print. PMID: 32576389 Abstract Background: Coffee is one of the most widely consumed beverages around the world. Dietary habits, specifically, coffee consumption has long been a suspected cause of hypertension. However, previous findings on coffee consumption and its association with the incidence of hypertension are not homogeneous and still inconsistent. Purpose: To examine the association of habitual coffee consumption with the risk of developing hypertension in a middle-aged Brazilian cohort. Methods: Data were from the multicenter prospective cohort "Brazilian Longitudinal Study for Adult Health - ELSA-Brasil". The cohort comprises 15,105 civil servants, aged 35-74 years at baseline, who were sampled from universities located in six Brazilian cities. For the present study, we analyzed data from 8780 participants initially free of hypertension during a mean follow-up of 3.9 years. The consumption of coffee was obtained at baseline using a previously validated semi-quantitative food frequency questionnaire (FFQ). Subsequently coffee intake was categorized into four categories (cups/day): never/almost never, ≤1, 1-3, and >3. Hypertension status was defined as a systolic blood pressure ≥140 mmHg or a diastolic blood pressure ≥90 mmHg, use of antihypertensive drug treatment, or both. Poisson regression model with a robust variance was performed to estimate relative risk (RR) and confidence interval (95% CI) for hypertension according to baseline coffee consumption. The effect of interaction between coffee consumption and smoking status was assessed. Results: Most participants (90%) drank coffee, and the median total coffee intake was 150 mL/day. A total of 1285 participants developed hypertension. Compared to participants who never or almost never drink coffee, the risk of hypertension was lower for individuals consuming 1-3 cups/day (RR 0.82, 95% CI: 0.68-0.97) (P for interaction=0.018). After stratification by smoking status the analysis revealed a decreased risk of hypertension in never smokers drinking 1-3 cups of coffee per day (RR 0.79, 95% CI: 0.64-0.98), whereas the hypertension risk among former and current smokers was not associated with coffee consumption significantly. Moreover, upper category of coffee drinking (>3 cups/day) the association was not significant for risk of hypertension. Conclusion: The association between coffee consumption and incidence of hypertension was related to smoking status. The beneficial effect of moderate coffee intake (1-3 cups/day) on risk of hypertension was observed only in never smokers. Keywords: Coffee; ELSA-Brasil; Hypertension; Prospective cohort; Smoking. Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial. de Groot S, Lugtenberg RT, Cohen D, Welters MJP, Ehsan I, Vreeswijk MPG, Smit VTHBM, de Graaf H, Heijns JB, Portielje JEA, van de Wouw AJ, Imholz ALT, Kessels LW, Vrijaldenhoven S, Baars A, Kranenbarg EM, Carpentier MD, Putter H, van der Hoeven JJM, Nortier JWR, Longo VD, Pijl H, Kroep JR; Dutch Breast Cancer Research Group (BOOG). Nat Commun. 2020 Jun 23;11(1):3083. doi: 10.1038/s41467-020-16138-3. PMID: 32576828 Abstract Short-term fasting protects tumor-bearing mice against the toxic effects of chemotherapy while enhancing therapeutic efficacy. We randomized 131 patients with HER2-negative stage II/III breast cancer, without diabetes and a BMI over 18 kg m-2, to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and during neoadjuvant chemotherapy. Here we show that there was no difference in toxicity between both groups, despite the fact that dexamethasone was omitted in the FMD group. A radiologically complete or partial response occurs more often in patients using the FMD (OR 3.168, P = 0.039). Moreover, per-protocol analysis reveals that the Miller&Payne 4/5 pathological response, indicating 90-100% tumor-cell loss, is more likely to occur in patients using the FMD (OR 4.109, P = 0.016). Also, the FMD significantly curtails chemotherapy-induced DNA damage in T-lymphocytes. These positive findings encourage further exploration of the benefits of fasting/FMD in cancer therapy. The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan. Yen K, Mehta HH, Kim SJ, Lue Y, Hoang J, Guerrero N, Port J, Bi Q, Navarrete G, Brandhorst S, Lewis KN, Wan J, Swerdloff R, Mattison JA, Buffenstein R, Breton CV, Wang C, Longo V, Atzmon G, Wallace D, Barzilai N, Cohen P. Aging (Albany NY). 2020 Jun 23;12. doi: 10.18632/aging.103534. Online ahead of print. PMID: 32575074 Abstract Humanin is a member of a new family of peptides that are encoded by short open reading frames within the mitochondrial genome. It is conserved in animals and is both neuroprotective and cytoprotective. Here we report that in C. elegans the overexpression of humanin is sufficient to increase lifespan, dependent on daf-16/Foxo. Humanin transgenic mice have many phenotypes that overlap with the worm phenotypes and, similar to exogenous humanin treatment, have increased protection against toxic insults. Treating middle-aged mice twice weekly with the potent humanin analogue HNG, humanin improves metabolic healthspan parameters and reduces inflammatory markers. In multiple species, humanin levels generally decline with age, but here we show that levels are surprisingly stable in the naked mole-rat, a model of negligible senescence. Furthermore, in children of centenarians, who are more likely to become centenarians themselves, circulating humanin levels are much greater than age-matched control subjects. Further linking humanin to healthspan, we observe that humanin levels are decreased in human diseases such as Alzheimer's disease and MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes). Together, these studies are the first to demonstrate that humanin is linked to improved healthspan and increased lifespan. Keywords: aging; humanin; mitochondria; peptides. Synchronization of the circadian clock by time-restricted feeding with progressive increasing calorie intake. Resemblances and differences regarding a sustained hypocaloric restriction. García-Gaytán AC, Miranda-Anaya M, Turrubiate I, López-De Portugal L, Bocanegra-Botello GN, López-Islas A, Díaz-Muñoz M, Méndez I. Sci Rep. 2020 Jun 22;10(1):10036. doi: 10.1038/s41598-020-66538-0. PMID: 32572063 Abstract Circadian rhythms are the product of the interaction of molecular clocks and environmental signals, such as light-dark cycles and eating-fasting cycles. Several studies have demonstrated that the circadian rhythm of peripheral clocks, and behavioural and metabolic mediators are re-synchronized in rodents fed under metabolic challenges, such as hyper- or hypocaloric diets and subjected to time-restricted feeding protocols. Despite the metabolic challenge, these approaches improve the metabolic status, raising the enquiry whether removing progressively the hypocaloric challenge in a time-restricted feeding protocol leads to metabolic benefits by the synchronizing effect. To address this issue, we compared the effects of two time-restricted feeding protocols, one involved hypocaloric intake during the entire protocol (HCT) and the other implied a progressive intake accomplishing a normocaloric intake at the end of the protocol (NCT) on several behavioural, metabolic, and molecular rhythmic parameters. We observed that the food anticipatory activity (FAA) was driven and maintained in both HCT and NCT. Resynchronization of hepatic molecular clock, free fatty acids (FFAs), and FGF21 was elicited closely by HCT and NCT. We further observed that the fasting cycles involved in both protocols promoted ketone body production, preferentially beta-hydroxybutyrate in HCT, whereas acetoacetate was favoured in NCT before access to food. These findings demonstrate that time-restricted feeding does not require a sustained calorie restriction for promoting and maintaining the synchronization of the metabolic and behavioural circadian clock, and suggest that metabolic modulators, such as FFAs and FGF21, could contribute to FAA expression. Leucine-Enriched Protein Supplementation Increases Lean Body Mass in Healthy Korean Adults Aged 50 Years and Older: A Randomized, Double-Blind, Placebo-Controlled Trial. Kang Y, Kim N, Choi YJ, Lee Y, Yun J, Park SJ, Park HS, Chung YS, Park YK. Nutrients. 2020 Jun 18;12(6):E1816. doi: 10.3390/nu12061816. PMID: 32570811 Abstract Early prevention of sarcopenia could be an important strategy for muscle retention, but most studies have focused on subjects aged 65 or older. Therefore, in this study we investigated the effects of leucine-enriched protein supplementation on muscle condition in a sample including late middle-aged adults. A 12-week intervention was performed for 120 healthy community-dwelling adults by providing either leucine-enriched protein supplement [leucine 3 g, protein mixture (casein 50% + whey 40% + soy 10%) 17 g, vitamin D 800IU (20 µg), calcium 300 mg, fat 1.1 g, carbohydrate 2.5 g] or isocaloric carbohydrate supplement twice per day. Appendicular skeletal muscle mass index (ASMI) and lean body mass (LBM) were measured by dual-energy X-ray absorptiometry. A total of 111 participants completed the study, with a dropout rate of 9.2%. LBM normalized by height and body weight (LBM/Wt) was significantly increased (p < 0.001) in the intervention group (0 wk: 633.9 ± 8.5 vs. 12 wk 636.9 ± 8.4 in the intervention group; 0 wk: 638.6 ± 8.3 vs. 12 wk: 632.9 ± 8.1 in the control group). In subgroup analyses, significant differences remained only in subjects between 50 and 64 years of age. We concluded that leucine-enriched protein supplementation can have beneficial effects by preventing muscle loss, mainly for late middle-aged adults. Keywords: lean body mass; leucine; protein; sarcopenia. Age-at-onset-dependent effects of sulfur amino acid restriction on markers of growth and stress in male F344 rats. Nichenametla SN, Mattocks DAL, Malloy VL. Aging Cell. 2020 Jun 22. doi: 10.1111/acel.13177. Online ahead of print. PMID: 32573078 Abstract Trade-offs in life-history traits are clinically and mechanistically important. Sulfur amino acid restriction (SAAR) extends lifespan. But whether this benefit comes at the cost of other traits including stress resistance and growth is unclear. We investigated the effects of SAAR on growth markers (body weight, IGF1, and IGFBP3) and physiological stresses. Male-F344 rats were fed control (0.86% Met) and SAAR (0.17% Met) diets starting at 2, 10, and 20 months. Rats were injected with keyhole-limpet-hemocyanin (KLH) to measure immune responses (anti-KLH-IgM, anti-KLH-IgG, and delayed-type-hypersensitivity [DTH]). Markers of ER stress (FGF21 and adiponectin), detoxification capacity (glutathione [GSH] concentrations, GSH-S-transferase [GST], and cytochrome-P450 -reductase [CPR] activities), and low-grade inflammation (C-reactive protein [CRP]) were also determined. SAAR decreased body weight, liver weight, food intake, plasma IGF1, and IGFBP3; the effect size diminished with increasing age-at-onset. SAAR increased FGF21 and adiponectin, but stress damage markers GRP78 and Xbp1s/us were unchanged, suggesting that ER stress is hormetic. SAAR increased hepatic GST activity despite lower GSH, but CPR activity was unchanged, indicative of enhanced detoxification capacity. Other stress markers were either uncompromised (CRP, anti-KLH-IgM, and DTH) or slightly lower (anti-KLH-IgG). Increases in stress markers were similar across all ages-at-onset, except for adiponectin, which peaked at 2 months. Overall, SAAR did not compromise stress responses and resulted in maximal benefits with young-onset. In survival studies, median lifespan extension with initiation at 52 weeks was 7 weeks (p = .05); less than the 33.5-week extension observed in our previous study with 7-week initiation. Findings support SAAR translational studies and the need to optimize Met dose based on age-at-onset. Keywords: ER stress; cysteine; glutathione; hormesis; lifespan; methionine; trade-offs; translational.
  12. AlPater

    Al's CR updates

    Intermittent fasting promotes adult hippocampal neuronal differentiation by activating GSK-3β in 3xTg-AD mice. Li W, Wu M, Zhang Y, Wei X, Zang J, Liu Y, Wang Y, Gong CX, Wei W. J Neurochem. 2020 Jun 23. doi: 10.1111/jnc.15105. Online ahead of print. PMID: 32578216 Abstract Moderate dietary restriction can ameliorate age-related chronic diseases such as Alzheimer's disease (AD) by increasing the expression of neurotrophic factors and promoting neurogenesis in the brain. Glycogen synthase kinase-3β (GSK-3β) signaling is essential for the coordination of progenitor cell proliferation and differentiation during brain development. The mechanisms by which GSK-3β is involved in dietary restriction induced neurogenesis and cognitive improvement remain unclear. Six-month-old male 3xTg-AD and wild type mice were fed on alternate days (intermittent fasting, IF) or ad libitum (AL) for 3 months. GSK-3β activity was regulated by bilaterally infusing lentiviral vectors carrying siRNA targeting GSK-3β into the dentate gyrus region of the hippocampus. Intermittent fasting promoted neuronal differentiation and maturation in the dentate gyrus and ameliorated recognize dysfunction in 3xTg-AD mice. These effects were reversed by siRNA targeting GSK-3β. After intermittent fasting, the insulin and protein kinase A signaling pathways were inhibited, while the AMP-activated protein kinase and brain-derived neurotrophic factor pathways were activated. These findings suggest that intermittent fasting can promote neuronal differentiation and maturation in the hippocampus by activating GSK-3β, thus improving learning and memory. Keywords: GSK-3β; Intermittent fasting; insulin pathway; neuronal differentiation.
  13. Handgrip strength and health outcomes: Umbrella review of systematic reviews with meta-analyses of observational studies. Soysal P, Hurst C, Demurtas J, Firth J, Howden R, Yang L, Tully MA, Koyanagi A, Ilie PC, López-Sánchez GF, Schwingshackl L, Veronese N, Smith L. J Sport Health Sci. 2020 Jun 18:S2095-2546(20)30075-2. doi: 10.1016/j.jshs.2020.06.009. Online ahead of print. PMID: 32565244 Abstract Purpose: The aim of the present study was to assess both the credibility and strength of evidence arising from systematic reviews with meta-analyses of observational studies on handgrip strength and health outcomes. Methods: An umbrella review of systematic reviews with meta-analyses of observational studies was conducted. We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their p values, 95% prediction intervals, heterogeneity, small-study effects, and excess significance. We graded the evidence from convincing (Class I) to weak (Class IV). Results: From 504 articles returned in a search of the literature, 8 systematic reviews were included in our review, with a total of 11 outcomes. Overall, 9 of the 11 of the outcomes reported nominally significant summary results (p < 0.05), with 4 associations surviving the application of the more stringent p value (p < 10-6). No outcome presented convincing evidence. Three associations showed Class II evidence (i.e., highly suggestive): (1) higher handgrip values at baseline were associated with a minor reduction in mortality risk in the general population (n = 34 studies; sample size = 1,855,817; relative risk (RR) = 0.72; 95% confidence interval (CI): 0.67-0.78), (2) cardiovascular death risk in mixed populations (n = 15 studies; RR = 0.84; 95%CI: 0.78-0.91), and (3) incidence of disability (n = 7 studies; RR = 0.76; 95%CI: 0.66-0.87). Conclusion: The present results show that handgrip strength is a useful indicator for general health status and specifically for early all-cause and cardiovascular mortality, as well as disability. To further inform intervention strategies, future research is now required to fully understand mechanisms linking handgrip strength scores to these health outcomes. Keywords: Handgrip strength; Health outcomes; Meta-analysis; Umbrella review. Systematic review of the prospective association of daily step counts with risk of mortality, cardiovascular disease, and dysglycemia. Hall KS, Hyde ET, Bassett DR, Carlson SA, Carnethon MR, Ekelund U, Evenson KR, Galuska DA, Kraus WE, Lee IM, Matthews CE, Omura JD, Paluch AE, Thomas WI, Fulton JE. Int J Behav Nutr Phys Act. 2020 Jun 20;17(1):78. doi: 10.1186/s12966-020-00978-9. PMID: 32563261 Abstract Background: Daily step counts is an intuitive metric that has demonstrated success in motivating physical activity in adults and may hold potential for future public health physical activity recommendations. This review seeks to clarify the pattern of the associations between daily steps and subsequent all-cause mortality, cardiovascular disease (CVD) morbidity and mortality, and dysglycemia, as well as the number of daily steps needed for health outcomes. Methods: A systematic review was conducted to identify prospective studies assessing daily step count measured by pedometer or accelerometer and their associations with all-cause mortality, CVD morbidity or mortality, and dysglycemia (dysglycemia or diabetes incidence, insulin sensitivity, fasting glucose, HbA1c). The search was performed across the Medline, Embase, CINAHL, and the Cochrane Library databases from inception to August 1, 2019. Eligibility criteria included longitudinal design with health outcomes assessed at baseline and subsequent timepoints; defining steps per day as the exposure; reporting all-cause mortality, CVD morbidity or mortality, and/or dysglycemia outcomes; adults ≥18 years old; and non-patient populations. Results: Seventeen prospective studies involving over 30,000 adults were identified. Five studies reported on all-cause mortality (follow-up time 4-10 years), four on cardiovascular risk or events (6 months to 6 years), and eight on dysglycemia outcomes (3 months to 5 years). For each 1000 daily step count increase at baseline, risk reductions in all-cause mortality (6-36%) and CVD (5-21%) at follow-up were estimated across a subsample of included studies. There was no evidence of significant interaction by age, sex, health conditions or behaviors (e.g., alcohol use, smoking status, diet) among studies that tested for interactions. Studies examining dysglycemia outcomes report inconsistent findings, partially due to heterogeneity across studies of glycemia-related biomarker outcomes, analytic approaches, and sample characteristics. Conclusions: Evidence from longitudinal data consistently demonstrated that walking an additional 1000 steps per day can help lower the risk of all-cause mortality, and CVD morbidity and mortality in adults, and that health benefits are present below 10,000 steps per day. However, the shape of the dose-response relation is not yet clear. Data are currently lacking to identify a specific minimum threshold of daily step counts needed to obtain overall health benefit. Keywords: Accelerometer; Diabetes; Physical activity; Physical activity guidelines; Prevention; Public health; Walking. Contributions of Modifiable Risk Factors to Dementia Incidence: A Bayesian Network Analysis. Liang JH, Lu L, Li JY, Qu XY, Li J, Qian S, Wang YQ, Jia RX, Wang CS, Xu Y. J Am Med Dir Assoc. 2020 Jun 17:S1525-8610(20)30325-X. doi: 10.1016/j.jamda.2020.04.006. Online ahead of print. PMID: 32563753 Review. Abstract Objective: To determine and compare the contributions of modifiable risk factors (RFs) with the prevention of dementia in older adults. Design: A systematic review and Bayesian network meta-analysis (NMA). The observational group was set as a reference to collect all existing RFs and compare them with each other. Setting and participants: An exhaustive and comprehensive literature search strategy was used to identify relevant prospective cohort studies from several online databases from their inception to May 1, 2019. Participants without dementia were adults aged greater than 50 years. Measures: The required data were extracted from the eligible studies to facilitate the Bayesian NMA. Results: Forty-three cohort studies with 277,294 participants were included in this NMA. Using the observation group as the reference, all defined RFs, except for antioxidants, were associated with lower risks of all-cause dementia [no sleep disturbances (odds ratio, OR 0.43, 95% credible interval, CrI 0.24-0.62), a high level of education (OR 0.50, 95% CrI 0.34-0.66), no history of diabetes (OR 0.57, 95% CrI 0.36-0.78), nonobese patients (OR 0.61, 95% CrI 0.39-0.83), no smoking history (OR 0.62, 95% CrI 0.45-0.79), living with family members (OR 0.67, 95% CrI 0.45-0.89), participation in physical exercise (OR 0.73, 95% CrI 0.46-0.94), abstinence from drinking (OR 0.78, 95% CrI 0.56-0.99), and no history of hypertension (OR 0.80, 95% CrI 0.65-0.96)]. Conclusions/relevance: The findings provide reliable support for the hypothesis that modifiable somatic and lifestyle factors are strong predictors of all-cause dementia. Saturated Fats and Health: A Reassessment and Proposal for Food-based Recommendations: JACC State-of -the-Art Review. Astrup A, Magkos F, Bier DM, Brenna JT, de Oliveira Otto MC, Hill JO, King JC, Mente A, Ordovas JM, Volek JS, Yusuf S, Krauss RM. J Am Coll Cardiol. 2020 Jun 16:S0735-1097(20)35687-4. doi: 10.1016/j.jacc.2020.05.077. Online ahead of print. PMID: 32562735 Review. Abstract The recommendation to limit dietary saturated fatty acid (SFA) intake has persisted despite mounting evidence to the contrary. Most recent meta-analyses of randomized trials and observational studies found no beneficial effects of reducing SFA intake on cardiovascular disease (CVD) and total mortality, and instead found protective effects against stroke. Although SFAs increase low-density lipoprotein (LDL)-cholesterol, in most individuals, this is not due to increasing levels of small, dense LDL particles, but rather larger LDL which are much less strongly related to CVD risk. It is also apparent that the health effects of foods cannot be predicted by their content in any nutrient group, without considering the overall macronutrient distribution. Whole-fat dairy, unprocessed meat, eggs and dark chocolate are SFA-rich foods with a complex matrix that are not associated with increased risk of CVD. The totality of available evidence does not support further limiting the intake of such foods. Keywords: cardiovascular disease; diet; food matrix; saturated fat. Personal activity intelligence and mortality - Data from the Aerobics Center Longitudinal Study. Nauman J, Sui X, Lavie CJ, Wen CP, Laukkanen JA, Blair SN, Dunn P, Arena R, Wisløff U. Prog Cardiovasc Dis. 2020 Jun 16:S0033-0620(20)30113-4. doi: 10.1016/j.pcad.2020.05.005. Online ahead of print. PMID: 32560967 Abstract Importance: Personal activity intelligence (PAI) is a novel activity metric that can be integrated into self-assessment heart rate devices, and translates heart rate variations during exercise into a weekly score. Previous studies relating to PAI have been conducted in the same populations from Norway where the PAI metric has been derived, limiting generalizability of the results. Objective: To test whether PAI is associated with total and cause-specific mortality in a large cohort from the United States. Design: Aerobics Center Longitudinal Study (ACLS) - a prospective cohort between January 1974 and December 2002 with a mean follow-up of 14.5 years. Setting: Population-based. Participants: 56,175 relatively healthy participants (26.5% women) who underwent extensive preventive medical examinations at Cooper Clinic (Dallas, TX). Exposure: Personal activity intelligence (PAI) score per week was estimated and divided into 4 groups (PAI scores of 0, ≤50, 51-99, and ≥100). Main outcomes and measures: Total and cause-specific mortality. Results: During a median follow-up time of 14.9 (interquartile range, 6.7-21.4) years, there were 3434 total deaths including 1258 cardiovascular (CVD) deaths. Compared with the inactive (0 PAI) group, participants with a baseline weekly ≥100 PAI had lower risk of mortality: adjusted hazard ratio (AHR), 0.79: 95% CI, 0.71-0.87 for all-cause mortality, and AHR, 0.72: 95% CI, 0.60-0.87 for CVD mortality among men; AHR, 0.85: 95% CI, 0.64-1.12 for all-cause mortality, and AHR, 0.48: 95% CI, 0.26-0.91 for CVD mortality among women. For deaths from ischemic heart disease (IHD), PAI score ≥100 was associated with lower risk in both men and women (AHR, 0.70: 95% CI, 0.55-0.88). Obtaining ≥100 weekly PAI was also associated with significantly lower risk of CVD mortality in pre-specified age groups, and in participants with known CVD risk factors. Participants with ≥100 weekly PAI gained 4.2 (95% CI, 3.5-4.6) years of life when compared with those who were inactive at baseline. Conclusions and relevance: PAI is associated with long-term all-cause, CVD, and IHD, mortality. Clinicians and the general population can incorporate PAI recommendations and thresholds in their physical activity prescriptions and weekly physical activity assessments, respectively, to maximize health outcomes. Key points: Question: What is the association between personal activity intelligence (PAI), a novel activity metric, and mortality in a large cohort from the United States? Findings: In this prospective study of 56,175 healthy participants at baseline, followed-up for a mean of 14.5 years, ≥100 PAI score/week was associated with significant 21% lower risk of all-cause and 30% lower risk of CVD mortality in comparison with inactive people. Participants with ≥100 PAI/week lived on average 4.2 years longer compared with inactive. Meaning: PAI is associated with long-term all-cause and CVD mortality. Clinicians and general population may incorporate PAI recommendations into weekly physical activity assessments to maximize CVD prevention. Keywords: Activity metric; Cardiovascular disease; Exercise; Mortality; Physical activity.
  14. AlPater

    Al's CR updates

    Combined effects of caloric restriction and fish oil attenuated anti-depressant and anxiolytic-like effects of fish oil: association with hippocampal BDNF concentrations. Correa CR, Schena C, Lopes SC, Prediger RD, Silva EL, Venske DKR, Ribeiro LC, Moreira JD. Behav Brain Res. 2020 Jun 16:112770. doi: 10.1016/j.bbr.2020.112770. Online ahead of print. PMID: 32561388 Abstract Omega-3-enriched fish oil (FO) and caloric restriction (CR) are nutritional therapeutic approaches that exert an important impact on brain function, behavior, memory, and neuroprotection. Here, we investigate the synergic effects of both therapeutic approaches combined (CR + FO) on behavior (memory, anxiety-like behavior, antidepressant-like behavior), as well as its association with hippocampal brain-derived neurotrophic factor (BDNF) concentrations. Adult male Wistar rats were divided into four dietary groups: Control group (C) - chow ad libitum; CR group - 30% CR, considering C group food intake; FO group - FO-enriched chow ad libitum; and CR + FO group - FO-enriched 30% CR chow. After 12 weeks of dietary treatment, behavioural analysis set was conducted, and hippocampal BDNF concentrations were measured. FO group presented anxiolytic-like and antidepressant-like behaviors as well as improved memory in the Morris' water maze. These effects were attenuated by the combined CR + FO treatment. FO group also presented higher BDNF concentrations. There was a positive association between the number of entries in the platform quadrant in the MWM and hippocampal BDNF concentrations (β = 0.39; R² = 0.15; p = 0.042) and an inverse association between forced swim immobility time and BDNF concentrations (β = -0.39; R² = 0.15; p = 0.041). Taken together, our data showed that the 12-week FO dietary treatment promoted anxiolytic-like and antidepressant-like behaviors as well as memory improvement, and these effects were associated with BDNF concentrations. Synergic effects of interventions attenuated FO-related behavioral responses and BDNF concentrations and probably reduced hippocampal neuroplasticity. Keywords: Anxiolytic-like behavior; Caloric restriction; Wistar rats; antidepressant-like behavior; fish oil.
  15. Prevalence, correlates and outcomes of multimorbidity among the middle-aged and elderly: Findings from the China Health and Retirement Longitudinal Study. Zhang Y, Zhou L, Liu S, Qiao Y, Wu Y, Ke C, Shen Y. Arch Gerontol Geriatr. 2020 Jun 4;90:104135. doi: 10.1016/j.archger.2020.104135. Online ahead of print. PMID: 32554217 Abstract Background: The multimorbidity associated with ageing has been prevalent worldwide and poses major challenges to the health care system. However, the research about multimorbidity in China is far from sufficient. Additionally, international studies on the influencing factors of multimorbidity and the impact on disability/mortality are still inconsistent. The aim of this study was to examine the prevalence, correlates and outcomes of multimorbidity among the middle-aged and elderly Chinese population. Methods: We used data from the China Health and Retirement Longitudinal Study (CHARLS). Logistic regression was performed to analyze the influencing factors of multimorbidity. The Cox proportional hazard model was used to evaluate the impact of multimorbidity on functional disability and all-cause mortality. Results: The prevalence of multimorbidity was 55.12 % in the whole study population and 65.60 % among people aged ≥ 65 years. Multimorbidity was significantly associated with old age (OR: 2.76, 95 % CI: 2.31-3.30), females (OR: 1.21, 95 % CI: 1.01-1.44), ex-smoker (OR: 2.07, 95 % CI: 1.58-2.72), ex-drinker (OR: 2.18, 95 % CI: 1.66-2.87), obesity (OR: 2.87, 95 % CI: 2.30-3.57), lower education (OR:1.32, 95 % CI: 1.08-1.61), living alone (OR: 1.26, 95 % CI: 1.02-1.55) and unemployment (OR: 1.66, 95 % CI: 1.11-2.48). Moreover, multimorbidity was correlated with disability (HR: 2.27, 95 % CI: 1.93-2.66) and all-cause mortality (HR: 1.95, 95 % CI: 1.36-2.80) after multivariable adjustment. Conclusions: Multimorbidity is highly prevalent in China and possesses significantly negative effects on health outcomes. Identification of the key population and tailored interventions on their modifiable risk factors should be paid much importance. Keywords: All-cause mortality; CHARLS; Multimorbidity; Risk factor. Exploring the effect of loneliness on all-cause mortality: Are there differences between older adults and younger and middle-aged adults? Lara E, Moreno-Agostino D, Martín-María N, Miret M, Rico-Uribe LA, Olaya B, Cabello M, Haro JM, Ayuso-Mateos JL. Soc Sci Med. 2020 May 30;258:113087. doi: 10.1016/j.socscimed.2020.113087. Online ahead of print. PMID: 32554229 Abstract Objective: This study aims to investigate the association between loneliness and all-cause mortality over a six-year follow-up period using the overall sample and by age groups (18-59 years and 60+ years). Method: Data from a longitudinal, prospective study of a nationally-representative sample of the Spanish non-institutionalized adult population were analysed (n = 4467). Mortality was ascertained via linkage to the National Death Index or obtained during the household visits. The UCLA Loneliness Scale was used to measure loneliness. Sex, age, education, physical activity, tobacco consumption, body mass index, disability, depression, living situation, and social participation were also considered as covariates. Multivariable Cox proportional hazard models were carried out. Results: A higher level of loneliness was not associated with mortality risk in fully covariate-adjusted models over the entire population (HR = 1.02; 95% CI = 0.94, 1.12). The interaction term between loneliness and age groups was significant, indicating that the rate for survival of loneliness varied by age (HR = 1.29; 95% CI = 1.02, 1.63 for young- and middle-aged individuals; HR = 0.96; 95% CI = 0.89, 1.04 for older adults). Conclusions: The development of interventions aimed at tackling loneliness among young- and middle-aged adults might contribute to a mortality risk reduction. Future research is warranted to test whether our results can be replicated. Keywords: Age differences; All-cause mortality; Loneliness; Population-based study; Spain. Association of Sedentary Behavior With Cancer Mortality in Middle-aged and Older US Adults. Gilchrist SC, Howard VJ, Akinyemiju T, Judd SE, Cushman M, Hooker SP, Diaz KM. JAMA Oncol. 2020 Jun 18. doi: 10.1001/jamaoncol.2020.2045. Online ahead of print. PMID: 32556069 Abstract Importance: Sedentary behavior is associated with several health outcomes, including diabetes, cardiovascular disease, and all-cause mortality. Less is known about the association between objectively measured sedentary behavior and cancer mortality, as well as the association with physical activity. Objective: To examine the association between accelerometer-measured sedentary behavior (total volume and accrual in prolonged, uninterrupted bouts) and cancer mortality. Design, setting, and participants: A prospective cohort study conducted in the contiguous US included 8002 black and white adults aged 45 years or older enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. The present analysis was performed from April 18, 2019, to April 21, 2020. Exposures: Sedentary time, light-intensity physical activity (LIPA), and moderate- to vigorous-intensity physical activity (MVPA) were measured using a hip-mounted accelerometer worn for 7 consecutive days. Main outcomes and measures: Cancer mortality. Results: Of the 8002 study participants, 3668 were men (45.8%); mean (SD) age was 69.8 (8.5) years. Over a mean (SD) follow-up of 5.3 (1.5) years, 268 participants (3.3%) died of cancer. In multivariable-adjusted models, including MVPA, greater total sedentary time was associated with a greater risk of cancer mortality (tertile 2 vs tertile 1: hazard ratio , 1.45; 95% CI, 1.00-2.11; tertile 3 vs tertile 1: HR, 1.52; 95% CI, 1.01-2.27). Longer sedentary bout duration was not significantly associated with greater cancer mortality risk: after adjustment for MVPA (tertile 2 vs tertile 1: HR, 1.26; 95% CI, 0.90-1.78; tertile 3 vs tertile 1: HR, 1.36; 95% CI, 0.96-1.93). Replacing 30 minutes of sedentary time with LIPA was significantly associated with an 8% (per 30 minutes: HR, 0.92; 95% CI, 0.86-0.97) lower risk of cancer mortality; MVPA was significantly associated with a 31% (per 30 minutes: HR, 0.69; 95% CI, 0.48-0.97) lower risk of cancer mortality. Conclusions and relevance: In this cohort study, greater sedentary time, as measured with accelerometry, appeared to be independently associated with cancer mortality risk. Replacing sedentary time with either LIPA or MVPA may be associated with a lower risk of cancer mortality. These findings suggest that the total volume of sedentary behavior is a potential cancer mortality risk factor and support the public health message that adults should sit less and move more to promote longevity. Preliminary evidence of effects of potassium chloride on a metabolomic path to diabetes and cardiovascular disease. Chatterjee R, Davenport CA, Kwee L, D'Alessio D, Svetkey LP, Lin PH, Slentz CA, Ilkayeva O, Johnson J, Edelman D, Shah SH. Metabolomics. 2020 Jun 18;16(7):75. doi: 10.1007/s11306-020-01696-w. PMID: 32556595 Abstract Introduction: Low potassium intake can affect cardiovascular disease (CVD) risk and cardiometabolic risk factors. Objective: We hypothesize that potassium chloride (KCl) supplementation can improve cardiovascular risk metabolomic profile. Methods: In this secondary analysis of a pilot randomized clinical trial (RCT) of 26 participants with prediabetes randomized to KCl or placebo, we performed targeted mass-spectrometry-based metabolomic profiling on baseline and 12-week (end-of-study) plasma samples. Principal component analysis (PCA) was used to reduce the many correlated metabolites into fewer, independent factors that retain most of the information in the original data. Results: Those taking KCl had significant reductions (corresponding to lower cardiovascular risk) in the branched-chain amino acids (BCAA) factor (P = 0.004) and in valine levels (P = 0.02); and non-significant reductions in short-chain acylcarnitines (SCA) factor (P = 0.11). Conclusions: KCl supplementation may improve circulating BCAA levels, which may reflect improvements in overall cardiometabolic risk profile. Clinical trials registry: Clinicaltrials.gov identifier: NCT02236598; https://clinicaltrials.gov/ct2/show/NCT02236598. Keywords: Branched-chain amino acids; Cardiovascular disease risk; Metabolites; Potassium chloride; Potassium supplements; Prediabetes. Combining a high dose of metformin with the SIRT1 activator, SRT1720, reduces lifespan in aged mice fed a high-fat diet. Palliyaguru DL, Minor RK, Mitchell SJ, Palacio HH, Licata JJ, Ward TM, Abulwerdi G, Elliott P, Westphal C, Ellis JL, Sinclair DA, Price NL, Bernier M, de Cabo R. J Gerontol A Biol Sci Med Sci. 2020 Jun 18:glaa148. doi: 10.1093/gerona/glaa148. Online ahead of print. PMID: 32556267 Abstract SRT1720, a sirtuin1-activator, and metformin (MET), an antidiabetic drug, confer health and lifespan benefits when administered individually. It is unclear whether combination of the two compounds could lead to additional benefits. Groups of 56-week-old C57BL/6J male mice were fed a high-fat diet (HFD) alone or supplemented with either SRT1720 (2 g/kg food), a high dose of MET (1% w/w food), or a combination of both. Animals were monitored for survival, body weight, food consumption, body composition and rotarod performance. Mice treated with MET alone did not have improved longevity, and lifespan was dramatically reduced by combination of MET with SRT1720. Although all groups of animals were consuming similar amounts of food, mice on MET or MET+SRT1720 showed a sharp reduction in body weight. SRT1720+MET mice also had lower percent body fat combined with better performance on the rotarod compared to controls. These data suggest that co-treatment of SRT1720 with MET is detrimental to survival at the doses used and, therefore, risk-benefits of combining lifespan-extending drugs especially in older populations needs to be systematically evaluated. Keywords: Metformin; SRT1720; Sirtuin; combination; lifespan.
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