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  • Birthday 06/09/1947

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  1. Comparing Canada to the US, two countries equidistant from Europe and China, https://www.worldometers.info/coronavirus/#countries indicates Canada, which implemented travel restrictions to hot-spots later than the US, has fewer infections and deaths. I live in Saskatoon, SK, where SK (population 1.1 million) has had as of yesterday, 193 cases, three in hospital, one in the ICU, 30 recovered and three deaths. Saskatoon (population 250,000) has had 94 cases, 3 in hospitals, 0 in the ICU and an unknown number of deaths. Grocery shopping here has been about the same as you describe, Dean. There are plexiglass shields for tellers and markings on the floor for social distancing. Toilet paper, flour, pastas and canned goods were in shorter than normal supply. Government officials have many more messages to the public on TV here than those from the American government on the American TV channels.
  2. Dietary diversity and all-cause mortality among Chinese adults aged 65 or older: A community-based cohort study. Tao L, Xie Z, Huang T. Asia Pac J Clin Nutr. 2020;29(1):152-160. doi: 10.6133/apjcn.202003_29(1).0020. PMID: 32229454 Abstract BACKGROUND AND OBJECTIVES: To evaluate the association between dietary diversity and all-cause mortality in older adults. METHODS AND STUDY DESIGN: 17,949 community-based elderly participants aged ≥65 years in China were included in this cohort study. The baseline consumption frequencies of nine food groups (meat, vegetables, fish, eggs, fruits, legumes, milk, tea, and nuts) were recorded, and the dietary diversity score (0-9) was calculated. Survival status and death date were collected during follow-up. Cox proportional-hazards models were used to assess the association between dietary diversity and all-cause mortality. RESULTS: We identified 8445 death events over 57,685 person-years of follow-up. Compared with participants in the lowest dietary diversity score group (score 0-1), higher dietary diversity scores were associated with lower mortality risk in univariate models. After adjusting for potential confounders, participants in the higher dietary diversity score group had a 9%-30% lower risk in all-cause mortality (p trend <0.001) compared with those in the lowest dietary diversity score group. The inverse relationship between dietary diversity score and all-cause mortality was also significant in four food groups (vegetables, fish, fruits, and nuts). Similar results were observed in sensitivity analyses. CONCLUSIONS: Our study showed that dietary diversity was inversely associated with all-cause mortality in the Chinese elderly, especially in the oldest old and men. Therefore, increasing dietary diversity may reduce mortality rates in the older population, and tailored interventions for improving dietary diversity are required to benefit health and survival in them. Self-rated health and objective health status as predictors of all-cause mortality among older people: a prospective study with a 5-, 10-, and 27-year follow-up. Wuorela M, Lavonius S, Salminen M, Vahlberg T, Viitanen M, Viikari L. BMC Geriatr. 2020 Mar 30;20(1):120. doi: 10.1186/s12877-020-01516-9. PMID: 32228464 Abstract BACKGROUND: Despite a non-specific nature of self-rated health (SRH), it seems to be a strong predictor of mortality. The aim of this study is to assess the association of SRH and objective health status (OH) with all-cause mortality in 70-year-old community-dwelling older people in Finland. METHODS: A prospective study with 5-, 10- and 27-year follow-ups. SRH (n = 1008) was assessed with a single question and OH (n = 962) by the Rockwood's Frailty Index (FI). To assess the association of SRH and OH with mortality, Cox regression model was used. RESULTS: Of the 1008 participants, 138 (13.7%), 319 (31.6%), and 932 deceased (86.3%) during the 5-, 10- and 27-year follow-ups, respectively. In unadjusted models, subjects with poor SRH had almost eightfold risk for mortality compared to those with good SRH during the 5-year follow-up; among those with poor OH, the risk was fourfold compared to those with good OH. In the 10-year-follow up, both poor SRH and poor OH predicted about fourfold risk for mortality compared to those with good health. During the 27-year follow-up, OH was a stronger predictor of mortality than SRH. Poor SRH, compared to good SRH, showed 95% sensitivity and 34% specificity for 5-year mortality; corresponding figures for OH were 54 and 80%, respectively. CONCLUSIONS: Single-item SRH seems to be able to capture almost the same as OH in predicting a short-term (less than 10 years) mortality risk among older adults in clinical settings. The use of SHR may also enhance the focus on patient-centered care. KEYWORDS: Frailty; Mortality; Objective health; Older people; Self-rated health Vitamin D and liver cancer risk: A meta-analysis of prospective studies. Guo XF, Zhao T, Han JM, Li S, Li D. Asia Pac J Clin Nutr. 2020;29(1):175-182. doi: 10.6133/apjcn.202003_29(1).0023. PMID: 32229457 Abstract BACKGROUND AND OBJECTIVES: The association between circulating vitamin D and liver cancer risk has been controversial on the basis of epidemiological studies. The aim of this study was to quantitatively evaluate this association with prospective studies. METHODS AND STUDY DESIGN: A systematic literature search was implemented in PubMed and Scopus databases up to June 2019. Using a random-effects model, the multivariate-adjusted relative risks (RRs) with corresponding 95% confidence interval (CI) were pooled for the highest versus lowest category. Trend estimation was conducted with a two-stage dose-response meta-analysis. RESULTS: Six independent prospective studies (992 liver cancer events and 60,811 participants) were included for data synthesis. The summary estimate showed that a higher circulating vitamin D was associated with lower risk of liver cancer (Summary RR=0.78; 95% CI: 0.63, 0.95; I2=53.6%, p=0.035). Dose-response analysis indicated that liver cancer was associated with 8% (95% CI: 0.89, 0.95) lower risk with a 10 nmol/L increment of circulating vitamin D concentration. CONCLUSIONS: The present study provides substantial evidence that a higher concentration of circulating vitamin D would have conferred protection against liver cancer. The Role of Protein Intake and its Timing on Body Composition and Muscle Function in Healthy Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Wirth J, Hillesheim E, Brennan L. J Nutr. 2020 Mar 31. pii: nxaa049. doi: 10.1093/jn/nxaa049. [Epub ahead of print] PMID: 32232404 Abstract BACKGROUND: Increased protein intake has been suggested to improve gains in muscle mass and strength in adults. Furthermore, the timing of protein intake has been discussed as a margin of opportunity for improved prevention measures. OBJECTIVE: This systematic review investigated the effect of protein supplementation on body composition and muscle function (strength and synthesis) in healthy adults, with an emphasis on the timing of protein intake. METHODS: Randomized controlled trials were identified using PubMed, Web of Science, CINAHL, and Embase, up to March 2019. For meta-analyses, data on lean body mass (LBM), handgrip strength, and leg press strength were pooled by age group (mean age 18-55 or >55 y) and timing of protein intake. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. RESULTS: Data from 65 studies with 2907 participants (1514 men and 1380 women, 13 unknown sex) were included in the review. Twenty-six, 8, and 24 studies were used for meta-analysis on LBM, handgrip strength, and leg press strength, respectively. The protein supplementation was effective in improving (mean difference; 95% CI) LBM in adults (0.62 kg; 0.36, 0.88) and older adults (0.46 kg; 0.23, 0.70), but not handgrip strength (older adults: 0.26 kg; -0.51, 1.04) and leg press strength (adults: 5.80 kg; -0.33, 11.93; older adults: 1.97 kg; -2.78, 6.72). Sensitivity analyses removing studies without exercise training had no impact on the outcomes. Data regarding muscle synthesis were scarce and inconclusive. Subgroup analyses showed no beneficial effect of a specific timing of protein intake on LBM, handgrip strength, and leg press strength. CONCLUSION: Overall, the results support the positive impact of protein supplementation on LBM of adults and older adults, independently of intake timing. Effects on muscle strength and synthesis are less clear and need further investigation. This systematic review was registered on PROSPERO as CRD42019126742. KEYWORDS: adults; body composition; elderly; lean body mass; muscle strength; muscle synthesis; obese; protein; timing of intake Effects of Leucine Administration in Sarcopenia: A Randomized and Placebo-controlled Clinical Trial. Martínez-Arnau FM, Fonfría-Vivas R, Buigues C, Castillo Y, Molina P, Hoogland AJ, van Doesburg F, Pruimboom L, Fernández-Garrido J, Cauli O. Nutrients. 2020 Mar 27;12(4). pii: E932. doi: 10.3390/nu12040932. PMID: 32230954 Abstract Treating sarcopenia in older individuals remains a challenge, and nutritional interventions present promising approaches in individuals that perform limited physical exercise. We assessed the efficacy of leucine administration to evaluate whether the regular intake of this essential amino acid can improve muscle mass, muscle strength and functional performance and respiratory muscle function in institutionalized older individuals. The study was a placebo-controlled, randomized, double-blind design in fifty participants aged 65 and over (ClinicalTrials.gov identifier NCT03831399). The participants were randomized to a parallel group intervention of 13 weeks' duration with a daily intake of leucine (6 g/day) or placebo (lactose, 6 g/day). The primary outcome was to study the effect on sarcopenia and respiratory muscle function. The secondary outcomes were changes in the geriatric evaluation scales, such as cognitive function, functional impairment and nutritional assessments. We also evaluated whether leucine administration alters blood analytical parameters and inflammatory markers. Administration of leucine was well-tolerated and significantly improves some criteria of sarcopenia in elderly individuals such as functional performance measured by walking time (p = 0.011), and improved lean mass index. For respiratory muscle function, the leucine-treated group improved significantly (p = 0.026) in maximum static expiratory force compared to the placebo. No significant effects on functional impairment, cognitive function or nutritional assessment, inflammatory cytokines IL-6, TNF-alpha were observed after leucine administration compared to the placebo. The use of l-leucine supplementation can have some beneficial effects on sarcopenia and could be considered for the treatment of sarcopenia in older individuals. KEYWORDS: elderly; muscle mass; muscle strength; nutrition; respiratory muscles; sarcopenia Effects of Diet on Sleep: A Narrative Review. Binks H, E Vincent G, Gupta C, Irwin C, Khalesi S. Nutrients. 2020 Mar 27;12(4). pii: E936. doi: 10.3390/nu12040936. Review. PMID: 32230944 Abstract Many processes are involved in sleep regulation, including the ingestion of nutrients, suggesting a link between diet and sleep. Aside from studies investigating the effects of tryptophan, previous research on sleep and diet has primarily focused on the effects of sleep deprivation or sleep restriction on diet. Furthermore, previous reviews have included subjects with clinically diagnosed sleep-related disorders. The current narrative review aimed to clarify findings on sleep-promoting foods and outline the effects of diet on sleep in otherwise healthy adults. A search was undertaken in August 2019 from the Cochrane, MEDLINE (PubMed), and CINAHL databases using the population, intervention, control, outcome (PICO) method. Eligible studies were classified based on emerging themes and reviewed using narrative synthesis. Four themes emerged: tryptophan consumption and tryptophan depletion, dietary supplements, food items, and macronutrients. High carbohydrate diets, and foods containing tryptophan, melatonin, and phytonutrients (e.g., cherries), were linked to improved sleep outcomes. The authors posit that these effects may be due in part to dietary influences on serotonin and melatonin activity. KEYWORDS: adults; dietary supplements; food; nutrients; sleep duration; sleep quality
  3. AlPater

    Al's CR updates

    Calorie Restriction Improves Physical Performance and Modulates the Antioxidant and Inflammatory Responses to Acute Exercise. Capó X, Martorell M, Ferrer MD, Sureda A, Pons V, Domingo JC, Drobnic F, Martínez-Rodríguez A, Leyva-Vela B, Sarabia JM, Herranz-López M, Roche E, Tur JA, Pons A. Nutrients. 2020 Mar 27;12(4). pii: E930. doi: 10.3390/nu12040930. PMID: 32230858 Abstract Our aim was to characterize the effects of calorie restriction on the anthropometric characteristics and physical performance of sportsmen and to evaluate the effects of calorie restriction and acute exercise on mitochondria energetics, oxidative stress, and inflammation. Twenty volunteer taekwondo practitioners undertook a calorie restriction of 30-40% on three alternate days a week for one month. Eleven volunteer sportsmen participated as controls. Both groups performed an energy efficiency test to evaluate physical performance, and samples were taken before and after exercise. The total weight of participants significantly decreased (5.9%) after calorie restriction, while the efficiency of work and the contributions of fat to obtain energy were enhanced by calorie restriction. No significant differences induced by acute exercise were observed in individual non-esterified fatty acid percentage or oxidative stress markers. Calorie restriction downregulated the basal gene expression of nitric oxide synthase, antioxidant enzymes, mitochondrial uncoupling proteins, and repairing stress proteins, but it enhanced the expression of sirtuins in peripheral blood mononuclear cells. In conclusion, one month of calorie restriction decreases body weight and increases physical performance, enhancing energy efficiency, moderating the antioxidant and inflammatory basal gene expression, and influencing its response to acute exercise. KEYWORDS: calorie restriction; exercise; fatty acids; oxidative stress; plasma Caloric restriction triggers morphofunctional remodeling of astrocytes and enhances synaptic plasticity in the mouse hippocampus. Popov A, Denisov P, Bychkov M, Brazhe A, Lyukmanova E, Shenkarev Z, Lazareva N, Verkhratsky A, Semyanov A. Cell Death Dis. 2020 Mar 30;11(3):208. doi: 10.1038/s41419-020-2406-3. PMID: 32231202 Abstract Calorie-restricted (CR) diet has multiple beneficial effects on brain function. Here we report morphological and functional changes in hippocampal astrocytes in 3-months-old mice subjected to 1 month of the diet. Whole-cell patch-clamp recordings were performed in the CA1 stratum (str.) radiatum astrocytes of hippocampal slices. The cells were also loaded with fluorescent dye through the patch pipette. CR did not affect the number of astrocytic branches but increased the volume fraction (VF) of distal perisynaptic astrocytic leaflets. The astrocyte growth did not lead to a decrease in the cell input resistance, which may be attributed to a decrease in astrocyte coupling through the gap junctions. Western blotting revealed a decrease in the expression of Cx43 but not Cx30. Immunocytochemical analysis demonstrated a decrease in the density and size of Cx43 clusters. Cx30 cluster density did not change, while their size increased in the vicinity of astrocytic soma. CR shortened K+ and glutamate transporter currents in astrocytes in response to 5 × 50 Hz Schaffer collateral stimulation. However, no change in the expression of astrocytic glutamate transporter 1 (GLT-1) was observed, while the level of glutamine synthetase (GS) decreased. These findings suggest that enhanced enwrapping of synapses by the astrocytic leaflets reduces glutamate and K+ spillover. Reduced spillover led to a decreased contribution of extrasynaptic N2B containing N-methyl-D-aspartate receptors (NMDARs) to the tail of burst-induced EPSCs. The magnitude of long-term potentiation (LTP) in the glutamatergic CA3-CA1 synapses was significantly enhanced after CR. This enhancement was abolished by N2B-NMDARs antagonist. Our findings suggest that astrocytic morphofunctional remodeling is responsible for enhanced synaptic plasticity, which provides a basis for improved learning and memory reported after CR.
  4. “It's the end of the world as we know it and I feel fine (time I had some time alone)”. -- R. E. M.
  5. Prospective Association between Whole Grain Consumption and Hypertension: The Furukawa Nutrition and Health Study. Kashino I, Eguchi M, Miki T, Kochi T, Nanri A, Kabe I, Mizoue T. Nutrients. 2020 Mar 26;12(4). pii: E902. doi: 10.3390/nu12040902. PMID: 32224906 Abstract Hypertension has become a major public health issue worldwide. Whole grains contain higher levels and a broader range of nutrients with potential health benefits and may decrease the risk of hypertension. However, no prospective studies have investigated this association in the high-income Asia Pacific region, which has the lowest whole grain intake worldwide. Thus, we examined the prospective association between whole grain consumption and the development of hypertension in Japan. Participants included 944 working Japanese adults aged 19-68 years who had no hypertension at baseline and completed a 3-year follow-up survey. Whole grain consumption was assessed via a self-administered dietary questionnaire. Multivariate logistic regression analysis was carried out to examine the association between whole grain consumption and hypertension, adjusting for potential confounding factors, such as sociodemographic, lifestyle, dietary, and occupational characteristics. After 3 years, 9.4% (86 cases) of the study participants had developed hypertension. More frequent whole grain consumption, classified as an intake frequency of "sometimes or always", was associated with lower odds of hypertension (multivariate-adjusted odds ratio: 0.36; 95% confidence interval: 0.16-0.83; p for trend = 0.04) compared with no consumption. Consuming more whole grains may decrease the risk of developing hypertension. KEYWORDS: Asians; Japan; blood pressure; cohort study; epidemiology; hypertension; whole grain Prospective Associations of Accelerometer-Measured Physical Activity and Sedentary Time With Incident Cardiovascular Disease, Cancer, and All-Cause Mortality. Dempsey PC, Strain T, Khaw KT, Wareham NJ, Brage S, Wijndaele K. Circulation. 2020 Mar 31;141(13):1113-1115. doi: 10.1161/CIRCULATIONAHA.119.043030. Epub 2020 Mar 30. No abstract available. PMID: 32223676 https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.119.043030 Handgrip strength is inversely associated with fatal cardiovascular and all-cause mortality events. Laukkanen JA, Voutilainen A, Kurl S, Araujo CGS, Jae SY, Kunutsor SK. Ann Med. 2020 Mar 30:1-25. doi: 10.1080/07853890.2020.1748220. [Epub ahead of print] PMID: 32223654 Abstract Purpose: We aimed to assess the associations of handgrip strength (HS) with cardiovascular and all-cause mortality and whether adding data on HS to cardiovascular disease (CVD) risk factors is associated with improvement in CVD mortality prediction.Design: Handgrip strength was assessed in a population-based sample of 861 participants aged 61-74 years at baseline. Relative HS was obtained by dividing the absolute value by body weight.Results: During a median (interquartile range) follow-up of 17.3 (12.6-18.4) years, 116 fatal coronary heart diseases (CHDs), 195 fatal CVDs, and 412 all-cause mortality events occurred. On adjustment for several risk factors, the hazard ratios (95% CIs) for fatal CHD, fatal CVD, and all-cause mortality were 0.59 (0.37-0.95), 0.59 (0.41-0.86), and 0.66 (0.51-0.84) respectively comparing extreme tertiles of relative HS. Adding relative HS to a CVD mortality risk prediction model containing established risk factors did not improve discrimination or reclassification using Harrel's C-index (C-index change: 0.0034; p = 0.65), integrated-discrimination-improvement (0.0059; p = 0.20), and net-reclassification-improvement (-1.31%; p = 0.74); however, there was a significant difference in in -2 log likelihood (p < 0.001).Conclusion: Relative HS is inversely associated with CHD, CVD and all-cause mortality events. Adding relative HS to conventional risk factors improves CVD risk assessment using sensitive measures of discrimination. KEY MESSAGESHandgrip strength assessment is simple, inexpensive and it takes only a few minutes to measure in clinical practice; however, its prognostic role for fatal cardiovascular outcomes on top of traditional risk factors in apparently healthy populations is uncertain.In a population-based prospective cohort study, good handgrip strength adjusted for body weight was associated with lower risk of fatal cardiovascular outcomes and the associations remained consistent across several clinically relevant subgroups.Handgrip strength may be a useful prognostic tool for fatal CHD and CVD events, in the general population. KEYWORDS: cardiovascular disease; handgrip strength; mortality; risk prediction CirculationVol. 139, No. Suppl_1 ORAL ABSTRACT PRESENTATIONS SESSION TITLE: EPIDEMIOLOGY OF MAJOR CARDIOVASCULAR EVENTS Abstract 007: Actigraphy-Measured Sleep Regularity and Risk of Incident Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis Tianyi Huang, Sara Mariani, Susan Redline Originally published6 Mar 2019https://doi.org/10.1161/circ.139.suppl_1.007Circulation. 2019;139:A007 Abstract Background: Prior studies have linked rotating night shift work to increased risk of cardiovascular disease (CVD). Irregular sleep schedules, characterized by high day-to-day variability in sleep duration or timing, represent possibly milder but much more common/chronic disruption of circadian rhythms in the general population. However, no prospective study to date has examined the association between sleep regularity and CVD outcomes. Methods: In the Multi-Ethnic Study of Atherosclerosis, 1,993 participants who were free of CVD completed 7-day wrist actigraphy at home for objective monitoring of sleep duration and quality between 2010 and 2013, and were prospectively followed through 2015. We assessed sleep regularity using the standard deviation (SD) of actigraphy-measured sleep duration and sleep onset timing across 7 days. Incident CVD was defined as total cardiovascular events including coronary heart disease, stroke, congestive heart failure, and cardiovascular death. Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for incident CVD according to SD of sleep duration and timing, adjusted for traditional CVD risk factors (e.g., sociodemographic factors, lifestyles and CVD biomarkers) and other sleep-related factors (e.g., average sleep duration, insomnia symptoms, daytime sleepiness, sleep-disordered breathing, chronotype and work schedules). Results: During a median follow-up of 4.0 years, 95 participants developed CVD events. Compared to participants with a 7-day sleep duration SD ≤60 min, the multivariable-adjusted HR (95% CI) for CVD was 1.12 (0.61, 2.07) for 61-90 min, 1.71 (0.94, 3.09) for 91-120 min, and 2.20 (1.22, 3.96) for >120 min. Every 1-hour increase in sleep duration SD was associated with 23% higher CVD risk (95% CI: 1.05, 1.45; p-trend=0.01). In contrast to this linear association with sleep duration variability, there appeared to be a threshold pattern for the association with SD of sleep onset timing. Compared to participants with a sleep timing SD ≤30 min, the multivariable-adjusted HR (95% CI) for CVD was 1.13 (0.60, 2.13) for 31-60 min, 1.15 (0.58, 2.31) for 61-90 min, and 2.07 (1.09, 3.94) for >90 min. CVD risk was 87% higher comparing sleep timing SD >90 min versus ≤90 min (95% CI: 1.19, 2.96; p=0.007). These associations did not differ significantly by age, sex, race/ethnicity, sleep duration or work schedules. Exclusion of current shift workers yielded similar results. Conclusion: Irregular sleep duration and timing may be novel risk factors for CVD, independent of traditional CVD risk factors and sleep quantity/quality. Given the increased prevalence of irregular sleep (e.g., due to mobile device use), our findings have important public health implications for CVD prevention and suggest value in evaluating the impact of sleep hygiene interventions aimed at improving sleep pattern consistency. >>>>>>>>>>>>>>>>>> Sleep Irregularity and Risk of Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis. Huang T, Mariani S, Redline S. J Am Coll Cardiol. 2020 Mar 10;75(9):991-999. doi: 10.1016/j.jacc.2019.12.054. PMID: 32138974 Abstract BACKGROUND: The cardiovascular system exhibits strong circadian rhythms to maintain normal functioning. Irregular sleep schedules, characterized by high day-to-day variability in sleep duration or timing, represent possibly milder but much more common and chronic disruption of circadian rhythms in the general population than shift work. OBJECTIVES: This study aimed to prospectively examine the association between sleep regularity and risk of cardiovascular disease (CVD). METHODS: In MESA (Multi-Ethnic Study of Atherosclerosis), 1,992 participants free of CVD completed 7-day wrist actigraphy for sleep assessment from 2010 to 2013 and were prospectively followed through 2016. The study assessed sleep regularity using the SD of actigraphy-measured sleep duration and sleep-onset timing across 7 days. Incident CVD included nonfatal and fatal cardiovascular events. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for incident CVD according to SD of sleep duration and timing, adjusted for traditional CVD risk factors (including CVD biomarkers) and other sleep-related factors (including average sleep duration). RESULTS: During a median follow-up of 4.9 years, 111 participants developed CVD events. The multivariable-adjusted HRs (95% confidence intervals) for CVD across categories of sleep duration SD were 1.00 (reference) for ≤60 min, 1.09 (0.62 to 1.92) for 61 to 90 min, 1.59 (0.91 to 2.76) for 91 to 120 min, and 2.14 (1.24 to 3.68) for >120 min (p trend = 0.002). Similarly, compared with participants with a sleep timing SD ≤30 min, the HRs (95% confidence intervals) for CVD were 1.16 (0.64 to 2.13) for 31 to 60 min, 1.52 (0.81 to 2.88) for 61 to 90 min, and 2.11 (1.13 to 3.91) for >90 min (p trend = 0.002). Exclusion of current shift workers yielded similar results. CONCLUSIONS: Irregular sleep duration and timing may be novel risk factors for CVD, independent of traditional CVD risk factors and sleep quantity and/or quality. KEYWORDS: cardiovascular disease; circadian rhythms; cohort study; risk factor; sleep patterns
  6. I wonder how many people with serious underlying conditions such as end stage kidney disease, end stage heart failure, treatment resistant hypertension, etc. who are infected by the virus are described by doctors or coroners to have died from the virus versus other disease. Re the flu -- Covid-19 comparison, I thought that information in https://www.vox.com/science-and-health/2020/3/13/21176735/covid-19-coronavirus-worse-than-flu-comparison pertained.
  7. A Prospective Evaluation of Serum Methionine-Related Metabolites in Relation to Pancreatic Cancer Risk in Two Prospective Cohort Studies. Huang JY, Luu HN, Butler LM, Midttun Ø, Ulvik A, Wang R, Jin A, Gao YT, Tan Y, Ueland PM, Koh WP, Yuan JM. Int J Cancer. 2020 Mar 29. doi: 10.1002/ijc.32994. [Epub ahead of print] PMID: 32222976 Abstract Deficiencies in methyl donor status may render DNA methylation changes and DNA damage, leading to carcinogenesis. Epidemiological studies reported that higher dietary intake of choline is associated with lower risk of pancreatic cancer, but no study has examined the association of serum choline and its metabolites with risk of pancreatic cancer. Two parallel case-control studies, one nested within the Shanghai Cohort Study (129 cases and 258 controls) and the other within the Singapore Chinese Health Study (58 cases and 104 controls), were conducted to evaluate the associations of baseline serum concentrations of choline, betaine, methionine, total methyl donors (i.e., sum of choline, betaine and methionine), dimethylglycine and trimethylamine N-oxide (TMAO) with pancreatic cancer risk. In the Shanghai cohort, odds ratios and 95% confidence intervals of pancreatic cancer for the highest quartile of choline, betaine, methionine, total methyl donors, and TMAO were 0.27 (0.11-0.69), 0.57 (0.31-1.05), 0.50 (0.26-0.96), 0.37 (0.19-0.73), and 2.81 (1.37-5.76), respectively, compared to the lowest quartile. The corresponding figures in the Singapore cohort were 0.85 (0.23-3.17), 0.50 (0.17-1.45), 0.17 (0.04-0.68), 0.33 (0.10-1.16), and 1.42 (0.50-4.04). The inverse associations of methionine and total methyl donors including choline, betaine and methionine with pancreatic cancer risk in both cohorts support that DNA repair and methylation play an important role against the development of pancreatic cancer. In the Shanghai cohort, TMAO, a gut microbiota-derived metabolite of dietary phosphatidylcholine, may contribute to higher risk of pancreatic cancer, suggesting a modifying role of gut microbiota in the dietary choline-pancreatic cancer risk association. KEYWORDS: DNA methylation; Pancreatic cancer; betaine; choline; methionine; microbiota; risk factors; trimethylamine N-oxide Cytomegalovirus and cancer-related mortality in the national health and nutritional examination survey. Okedele OO, Nelson HH, Oyenuga ML, Thyagarajan B, Prizment A. Cancer Causes Control. 2020 Mar 28. doi: 10.1007/s10552-020-01296-y. [Epub ahead of print] PMID: 32222844 Abstract PURPOSE: Cytomegalovirus (HCMV) is a common viral infection that shapes lifelong immunity. A history of infection with HCMV has been associated with many chronic diseases, including cancer. In addition, prospective cohort studies have established that HCMV is associated with all-cause mortality. However, there are limited data regarding HCMV and cancer mortality. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) III study (1988-1994): subjects aged 18 to 98, who had HCMV serology results, did not report having cancer at baseline, and were eligible for mortality follow-up (n = 14,498). Mortality was ascertained until December 2011 using National Death Index (NDI) linkage. RESULTS: The unadjusted risk of all-cancer mortality was higher in HCMV seropositive individuals (HR 2.74, 95% CI 2.05-3.64). This association was attenuated after adjusting for age (HR 1.39, 95% CI 1.02-1.92), and other covariates (age, sex, race/ethnicity, smoking status, BMI, education, and C-reactive protein (CRP); HR 1.21, 95% CI 0.91-1.81). There was a statistically significant interaction between HCMV and sex (p = 0.01): HCMV seropositivity was associated with increased cancer mortality in men (HR 1.65, 95% CI 0.99-2.73) but not in women (HR 0.95, 95% CI 0.59-1.54). CONCLUSION(S): Consistent with prior reports, HCMV seropositivity may be associated with an increased risk of cancer-related mortality but the association is partially driven by socioeconomic status and other risk factors. Future research is needed to determine whether HCMV is a risk factor for cancer, as well as identify the specific cancer types where HCMV increases mortality. KEYWORDS: Cancer; Cancer mortality; Cytomegalovirus; Mortality; Seropositivity Plant-based and animal-based low-carbohydrate diets and risk of hepatocellular carcinoma among US men and women. Liu Y, Yang W, VoPham T, Ma Y, Simon TG, Gao X, Chan AT, Meyerhardt JA, Giovannucci EL, Zhang X. Hepatology. 2020 Mar 29. doi: 10.1002/hep.31251. [Epub ahead of print] PMID: 32222996 Abstract Little is known about the role of low-carbohydrate diets (LCDs) in the development of hepatocellular carcinoma (HCC). We prospectively evaluated the associations between plant-based and animal-based LCDs and risk of HCC in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Dietary intake was assessed every 4 years using validated food frequency questionnaires. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). HRs are shown for a 1-standard deviation (SD) increment with variable modelled as continuous. During 3,664,769 person years of follow-up, there were 156 incident HCC cases. Although there were no associations between overall or animal-based LCD score and risk of HCC, plant-based LCD score was inversely associated with HCC risk (HR: 0.83; 95% CI: 0.70-0.98; Ptrend =0.03). Carbohydrate intake, especially from refined grains (HR: 1.18; 95% CI: 1.00-1.39; Ptrend =0.04) was positively, while plant fat (HR: 0.78; 95% CI: 0.65-0.95; Ptrend =0.01) was inversely associated with HCC risk. Substituting 5% of energy from plant fat and protein for carbohydrate (HR: 0.74; 95% CI: 0.58-0.93; Ptrend =0.01) or refined grains (HR: 0.70; 95% CI: 0.55-0.90; Ptrend =0.006) was associated with lower HCC risk. In conclusion, a plant-based LCD and dietary restriction of carbohydrate from refined grains were associated with a lower risk of HCC. Substituting plant fat and protein for carbohydrate, particularly refined grains, may decrease HCC incidence. Our findings support a potential benefit in emphasizing plant sources of fat and protein in the diet for HCC primary prevention. Additional studies that carefully consider hepatitis B and C virus infections and chronic liver diseases are needed to confirm our findings. KEYWORDS: hepatocellular carcinoma; macronutrients; plant-based low-carbohydrate diets; prospective cohort; specific food sources Association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance in older adults: National Health and nutrition examination Survey (NHANES) 2011-2014. Dong X, Li S, Chen J, Li Y, Wu Y, Zhang D. Nutr J. 2020 Mar 28;19(1):25. doi: 10.1186/s12937-020-00547-7. PMID: 32222145 Abstract BACKGROUND: Current evidence on the association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance is inconsistent. Therefore, the aim is to explore the association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance in the U.S. noninstitutionalized population of older adults. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Intakes of ω-3 and ω-6 fatty acids were obtained through two 24-h dietary recalls and were adjusted by energy. Cognitive performance was evaluated by the Consortium to Establish a Registry for Alzheimer's disease (CERAD) Word Learning sub-test, Animal Fluency test and Digit Symbol Substitution Test (DSST). For each cognitive test, people who scored lower than the lowest quartile in each age group were defined as having low cognitive performance. Binary logistic regression and restricted cubic spline models were applied to evaluate the association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance. RESULTS: A total of 2496 participants aged 60 years or older were included. In the full-adjusted model, the odds ratios (ORs) with 95% confidence interval (CI) of CERAD test score, Animal Fluency test score and DSST test score were 0.58 (0.38-0.88), 0.68 (0.47-0.99) and 0.59 (0.37-0.92) for the highest versus lowest tertile of dietary ω-3 fatty acids intake, respectively; the ORs with 95% CI of CERAD test score, Animal Fluency test score and DSST test score were 0.48 (0.31-0.75), 0.60 (0.40-0.92) and 0.50 (0.34-0.75) for the highest versus lowest tertile of dietary ω-6 fatty acids intake, respectively. The association between ω-6: ω-3 ratio and cognitive performance was not statistically significant in three tests. In dose-response relationship analysis, L-shaped associations were apparent for ω-3 and ω-6 fatty acids intake with CERAD test score, Animal Fluency test score and DSST test score. CONCLUSIONS: Dietary ω-3 and ω-6 fatty acids intake might be inversely associated with low cognitive performance. KEYWORDS: Cognitive performance; Dietary ω-3 fatty acids; Dietary ω-6 fatty acids; Dose-response; ω-6: ω-3 ratio The effect of cinnamon supplementation on blood pressure in adults: A systematic review and meta-analysis of randomized controlled trials. Hadi A, Campbell MS, Hassani B, Pourmasoumi M, Salehi-Sahlabadi A, Hosseini SA. Clin Nutr ESPEN. 2020 Apr;36:10-16. doi: 10.1016/j.clnesp.2020.01.002. Epub 2020 Jan 20. Review. PMID: 32220351 Abstract BACKGROUND & AIMS: Several clinical trials have shown that cinnamon can reduce blood pressure, but the results are controversial. Therefore, we conducted a systematic review and meta-analysis to provide a more precise estimate of the overall effects of cinnamon supplementation on blood pressure in adults. METHODS: We searched PubMed, Scopus, Cochrane Library, ISI Web of Science, and Google Scholar databases through September 2019 to identify randomized clinical trials (RCTs) investigating the effect of cinnamon supplementation on blood pressure. Data were pooled by using the random-effects model, and weighted mean difference (WMD) was considered as the summary effect size. Sensitivity analysis was conducted using the leave-one-out method. RESULTS: Meta-analysis of 9 RCTs with 641 participants showed significant reductions in both systolic (WMD: -5.17 mmHg, 95% CI: -9.35 to -0.99, P = 0.01) and diastolic blood pressure (WMD: -3.36 mmHg, 95% CI: -5.67 to -1.04, P ≤ 0.001) after cinnamon supplementation. Subgroup analyses indicated that these results were significant only when cinnamon was administered at the dosages of ≤2 g/day, for a period longer than 8 weeks, and in participants with a baseline BMI of ≥30 kg/m2. CONCLUSION: The present meta-analysis suggests that cinnamon supplementation can improve blood pressure by a modest degree. However, due to limited availability of studies with hypertensive cases and relatively small sample sizes of available studies, well designed trials with adequate sample sizes aimed at hypertensive populations are recommended. Effect of dark chocolate on flow-mediated dilatation: Systematic review, meta-analysis, and dose-response analysis of randomized controlled trials. Ebaditabar M, Djafarian K, Saeidifard N, Shab-Bidar S. Clin Nutr ESPEN. 2020 Apr;36:17-27. doi: 10.1016/j.clnesp.2019.10.017. Epub 2019 Nov 16. Review. PMID: 32220363 Abstract BACKGROUND & AIMS: We aimed to investigate the effect of dark chocolate on flow-mediated dilatation (FMD) using randomized clinical trials. METHODS: In order to find relevant papers, PubMed and Scopus were searched up to November 2018. Mean differences of eligible trials were pooled using random-effects models (the Der Simonian-Laird estimator). Subgroup analysis was conducted to assess the potential source of heterogeneity. Fractional polynomial modeling was used to explore dose-response relationships. RESULTS: Seventeen studies involving 615 participants assessed the effect of dark chocolate and six included studies involving 179 participants investigated the effect of flavonoids on FMD. Chronic consumption of dark chocolate and flavan-3-ols both increased FMD (0.69, 95% CI 0.22-1.16, p < 0.001, 1.16, 95% CI 0.52-1.80 p = 0.001, respectively). Pooling chronic consumption of dark chocolate and flavonoids improved FMD (p < 0.001) with significant heterogeneity among studies (p < 0.001; I2 = 64.2%). Type of intervention (flavonoid or cocoa, p = 0.230-dark chocolate, p < 0.001) was a source of heterogeneity. Also, we found that acute consumption of dark chocolate (p < 0.001) and both dark chocolate and flavonoids (p < 0.001) had beneficial effects on FMD. Consumption of flavonoids more than 40 g/day increases FMD with the highest mean of FMD in doses around 40-60 g/day. A non-linear dose-response has been also found after the chronic consumption of dark chocolate on FMD with a greater reduction in doses lower than 20 g/day. CONCLUSION: Current evidence indicated the beneficial effect of acute and chronic consumption of dark chocolate and flavonoids on FMD. Non-linear associations should be considered when investigating the effects of dietary intakes on FMD. KEYWORDS: Dark chocolate; Endothelial function; Flow mediated dilation; Meta-analysis
  8. Differential responses of white adipose tissue and brown adipose tissue to calorie restriction during aging. Sheng Y, Xia F, Chen L, Lv Y, Lv S, Yu J, Liu J, Ding G. J Gerontol A Biol Sci Med Sci. 2020 Mar 28. pii: glaa070. doi: 10.1093/gerona/glaa070. [Epub ahead of print] PMID: 32222773 Abstract Age-related adipose tissue dysfunction is potentially important in the development of insulin resistance and metabolic disorder. Caloric restriction (CR) is a robust intervention to reduce adiposity, improve metabolic health, and extend healthy lifespan. Both white adipose tissue (WAT) and brown adipose tissue (BAT) are involved in energy homeostasis. CR triggers the beiging of WAT in young mice, however, the effects of CR on beiging of WAT and function of BAT during aging are unclear. This study aimed to investigate how age and CR impact the beiging of WAT, the function of BAT, and metabolic health in mice. C57BL/6 mice were fed CR diet (40% less than the ad libitum diet) for 3 months initiated in young (3 months), middle-aged (12 months), and old (19 months) stage. We found age-related changes in different types of adipose tissue including adipocyte enlargement, declined beiging of WAT, and declined thermogenic and β-oxidational function of BAT. Moreover, CR attenuated age-associated adipocyte enlargement and prevented the age-related decline in beiging potential of WAT. These protective effects on the beiging potential were significant in iWAT at all three ages, which were significant in eWAT at young and old age. In contrast, thermogenic and β-oxidational function of BAT further declined after CR in the young age group. In conclusion, our findings reveal the contribution of WAT beiging decline to age-related metabolic disorder, and suggest nutritional intervention, specifically targeting WAT beiging, as an effective approach to metabolic healthy during aging. KEYWORDS: BAT; beiging; calorie restriction; eWAT; iWAT
  9. The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials. Kuang X, Liu C, Guo X, Li K, Deng Q, Li D. Food Funct. 2020 Mar 27. doi: 10.1039/c9fo03063h. [Epub ahead of print] PMID: 32219282 Abstract BACKGROUND: Previous studies did not draw a consistent conclusion about the effects of vitamin K combined with vitamin D on human skeletal quality. METHOD AND FINDINGS: A comprehensive search on Web of Science, PubMed, Embase and the Cochrane Library (from 1950 to February 2020) and bibliographies of relevant articles was undertaken, with the meta-analysis of eight randomized controlled trials (RCTs) including a total of 971 subjects. Vitamin K combined with vitamin D significantly increased the total bone mineral density (BMD): the pooled effect size was 0.316 [95% CI (confidence interval), 0.031 to 0.601]. A significant decrease in undercarboxylated osteocalcin (-0.945, -1.113 to -0.778) can be observed with the combination of vitamin K and D. Simultaneously, subgroup analysis showed that K2 or vitamin K (not specified) supplement was less than 500 μg d-1, which when combined with vitamin D can significantly increase the total BMD compared with the control group fed a normal diet or the group with no treatment (0.479, 0.101 to 0.858 and 0.570, 0.196 to 0.945). CONCLUSIONS: The combination of vitamin K and D can significantly increase the total BMD and significantly decrease undercarboxylated osteocalcin, and a more favorable effect is expected when vitamin K2 is used. Shotgun Metagenomics of Gut Microbiota in Humans with up to Extreme Longevity and the Increasing Role of Xenobiotic Degradation. Rampelli S, Soverini M, D'Amico F, Barone M, Tavella T, Monti D, Capri M, Astolfi A, Brigidi P, Biagi E, Franceschi C, Turroni S, Candela M. mSystems. 2020 Mar 24;5(2). pii: e00124-20. doi: 10.1128/mSystems.00124-20. PMID: 32209716 Abstract The gut microbiome of long-lived people display an increasing abundance of subdominant species, as well as a rearrangement in health-associated bacteria, but less is known about microbiome functions. In order to disentangle the contribution of the gut microbiome to the complex trait of human longevity, we here describe the metagenomic change of the human gut microbiome along with aging in subjects with up to extreme longevity, including centenarians (aged 99 to 104 years) and semisupercentenarians (aged 105 to 109 years), i.e., demographically very uncommon subjects who reach the extreme limit of the human life span. According to our findings, the gut microbiome of centenarians and semisupercentenarians is more suited for xenobiotic degradation and shows a rearrangement in metabolic pathways related to carbohydrate, amino acid, and lipid metabolism. Collectively, our data go beyond the relationship between intestinal bacteria and physiological changes that occur with aging by detailing the shifts in the potential metagenomic functions of the gut microbiome of centenarians and semisupercentenarians as a response to progressive dietary and lifestyle modifications.IMPORTANCE The study of longevity may help us understand how human beings can delay or survive the most frequent age-related diseases and morbidities. In this scenario, the gut microbiome has been proposed as one of the variables to monitor and possibly support healthy aging. Indeed, the disruption of host-gut microbiome homeostasis has been associated with inflammation and intestinal permeability as well as a general decline in bone and cognitive health. Here, we performed a metagenomic assessment of fecal samples from semisupercentenarians, i.e., 105 to 109 years old, in comparison to young adults, the elderly, and centenarians, shedding light on the longest compositional and functional trajectory of the human gut microbiome with aging. In addition to providing a fine taxonomic resolution down to the species level, our study emphasizes the progressive age-related increase in degradation pathways of pervasive xenobiotics in Western societies, possibly as a result of a supportive process within the molecular continuum characterizing aging. KEYWORDS: aging; extreme longevity; metagenome; microbiome; xenobiotics Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability. Matsuno Y, Atsumi Y, Alauddin M, Rana MM, Fujimori H, Hyodo M, Shimizu A, Ikuta T, Tani H, Torigoe H, Nakatsu Y, Tsuzuki T, Komai M, Shirakawa H, Yoshioka KI. Sci Rep. 2020 Mar 25;10(1):5388. doi: 10.1038/s41598-020-62292-5. PMID: 32214146 Abstract Genomic destabilisation is associated with the induction of mutations, including those in cancer-driver genes, and subsequent clonal evolution of cells with abrogated defence systems. Such mutations are not induced when genome stability is maintained; however, the mechanisms involved in genome stability maintenance remain elusive. Here, resveratrol (and related polyphenols) is shown to enhance genome stability in mouse embryonic fibroblasts, ultimately protecting the cells against the induction of mutations in the ARF/p53 pathway. Replication stress-associated DNA double-strand breaks (DSBs) that accumulated with genomic destabilisation were effectively reduced by resveratrol treatment. In addition, resveratrol transiently stabilised the expression of histone H2AX, which is involved in DSB repair. Similar effects on the maintenance of genome stability were observed for related polyphenols. Accordingly, we propose that polyphenol consumption can contribute to the suppression of cancers that develop with genomic instability, as well as lifespan extension. Habitual tub bathing and risks of incident coronary heart disease and stroke. Ukai T, Iso H, Yamagishi K, Saito I, Kokubo Y, Yatsuya H, Muraki I, Eshak ES, Sawada N, Tsugane S. Heart. 2020 Mar 24. pii: heartjnl-2019-315752. doi: 10.1136/heartjnl-2019-315752. [Epub ahead of print] PMID: 32209614 Abstract OBJECTIVE: Tub bathing is considered to have a preventive effect against cardiovascular disease (CVD) by improving haemodynamic function. However, no prospective studies have investigated the long-term effects of tub bathing with regard to CVD risk. METHODS: A total of 30 076 participants aged 40-59 years with no history of CVD or cancer were followed up from 1990 to 2009. Participants were classified by bathing frequency: zero to two times/week, three to four times/week and almost every day. The HRs of incident CVD were estimated using Cox proportional hazards models after adjusting for traditional CVD risk factors and selected dietary factors. RESULTS: During 538 373 person-years of follow-up, we documented a total of 2097 incident cases of CVD, comprising 328 coronary heart diseases (CHDs) (275 myocardial infarctions and 53 sudden cardiac deaths) and 1769 strokes (991 cerebral infarctions, 510 intracerebral haemorrhages, 255 subarachnoid haemorrhages and 13 unclassified strokes). The multivariable HRs (95% CIs) for almost daily or every day versus zero to two times/week were 0.72 (0.62 to 0.84, trend p<0.001) for total CVD; 0.65 (0.45 to 0.94, trend p=0.065) for CHD; 0.74 (0.62 to 0.87, trend p=0.005) for total stroke; 0.77 (0.62 to 0.97, trend p=0.467) for cerebral infarction; and 0.54 (0.40 to 0.73, trend p<0.001) for intracerebral haemorrhage. No associations were observed between tub bathing frequency and risk of sudden cardiac death or subarachnoid haemorrhage. CONCLUSION: The frequency of tub bathing was inversely associated with the risk of CVD among middle-aged Japanese. KEYWORDS: acute myocardial infarction; cardiac risk factors and prevention; stroke Plasma magnesium and the risk of new-onset hyperuricemia in hypertensive patients. Cao J, Zhang J, Zhang Y, Li H, Jiang C, Lin T, Zhou Z, Song Y, Liu C, Liu L, Wang B, Li J, Zhang Y, Cui Y, Huo Y, Wang X, Zhang H, Qin X, Xu X. Br J Nutr. 2020 Mar 26:1-22. doi: 10.1017/S0007114520001099. [Epub ahead of print] PMID: 32213225 Abstract We aimed to evaluate the relationship of plasma magnesium with the risk of new-onset hyperuricemia, and examine any possible effect modifiers in hypertensive patients. This is a post-hoc analysis of the Uric acid (UA) Sub-study of the China Stroke Primary Prevention Trial (CSPPT). A total of 1685 participants were included in the current study. The main outcome was new-onset hyperuricemia defined as a UA concentration ≥417 μmol/L in men or ≥357 μmol/L in women. The secondary outcome was a change in UA concentration defined as UA at the exit visit minus that at baseline. During a median follow-up duration of 4.3 years, new-onset hyperuricemia occurred in 290 (17.2%) participants. There was a significantly inverse relation of plasma magnesium with the risk of new-onset hyperuricemia (per SD increment; OR, 0.85; 95%CI: 0.74, 0.99) and change in UA levels (per SD increment; β, -3.96 μmol/L; 95%CI: -7.14, -0.79). Consistently, when plasma magnesium was analyzed as tertiles, a significantly lower risk of new-onset hyperuricemia (OR, 0.67; 95%CI: 0.48, 0.95) and less increase in UA levels (β, -8.35μmol/L; 95%CI: -16.12, -0.58) were found among participants in tertile 3 (≥885.5 μmol/L) compared with those in tertile 1 (<818.9 μmol/L). Similar trends were found in males and females. Higher plasma magnesium levels were associated with a decreased risk of new-onset hyperuricemia in hypertensive adults. KEYWORDS: Magnesium; hypertensive patients; hyperuricemia; uric acid The Dose-Response Relationship between Gamma-Glutamyl Transferase and Risk of Diabetes Mellitus Using Publicly Available Data: A Longitudinal Study in Japan. Zhao W, Tong J, Liu J, Liu J, Li J, Cao Y. Int J Endocrinol. 2020 Feb 21;2020:5356498. doi: 10.1155/2020/5356498. eCollection 2020. PMID: 32215009 Abstract PURPOSE: The purpose of this study was to examine the association between baseline serum gamma-glutamyl transferase (GGT) and incident diabetes mellitus and to explore their dose-response relationship in a cohort of Japanese adults. Patients and Methods. Data were drawn from the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) study between 2004 and 2015, including hierarchical information on participants ≥18 years of age without diabetes mellitus, preexisting diabetes mellitus, heavy alcohol drinking, or other liver diseases (e.g., hepatitis B/C). The final analytic sample included 15464 participants, 373 of who were diagnosed as diabetes mellitus with a maximum 13-year follow-up. The risk of incident diabetes mellitus according to baseline serum GGT was estimated using multivariable Cox proportional hazards models and a two-piecewise linear regression model was developed to find out the threshold effect. RESULTS: Being in the highest quintile versus the lowest quintile of GGT levels was associated with an almost twofold increased risk of incident diabetes mellitus (hazard ratio 1.83 (95% CI 1.06, 3.15)), independent of age, gender, smoking status, alcohol intake, BMI, SBP, triglycerides, fatty liver, ALT, AST, and fasting plasma glucose. Further analysis revealed a positive curvilinear association between GGT and incident diabetes mellitus, with a saturation effect predicted at 24 IU/L. When serum GGT level was less than 24 IU/L, the risk of developing diabetes mellitus increased significantly with an increase in serum GGT levels (HR 1.04 (1.02, 1.07), P=0.0017). Besides, the association was more significant in nonsmoking participants than ex- or current-smokers (P=0.0017). Besides, the association was more significant in nonsmoking participants than ex- or current-smokers (P for interaction = 0.0378). CONCLUSION: Serum GGT level was a significant predictor of subsequent risk of diabetes mellitus, which increased by 4% for every 1 IU/L increase in GGT when GGT was less than 24 IU/L.
  10. AlPater

    Al's CR updates

    Low costs of adaptation to dietary restriction. Moger-Reischer RZ, Snider EV, McKenzie KL, Lennon JT. Biol Lett. 2020 Mar;16(3):20200008. doi: 10.1098/rsbl.2020.0008. Epub 2020 Mar 25. PMID: 32208792 Abstract Dietary restriction (DR) is the most successful and widespread means of extending organismal lifespan. However, the evolutionary basis of life extension under DR remains uncertain. The traditional evolutionary explanation is that when organisms experience DR, they allocate endogenous resources to survival and postpone reproduction until conditions improve. However, this life-extension strategy should be maladaptive if DR continues for multiple generations due to trade-offs between longevity and reproduction. To test this prediction, we subjected the budding yeast Saccharomyces cerevisiae to 1800 generations of evolution on restricted versus non-restricted diets. Adaptation to a non-restricted diet improved reproductive fitness by 57%, but provided a much smaller (14%) advantage on a restricted diet. By contrast, adaptation to DR resulted in an approximately 35% increase in reproductive fitness on both restricted and non-restricted diets. Importantly, the life-extending effect of DR did not decrease following long-term evolution on the restricted diet. Thus, contrary to theoretical expectations, we found no evidence that the life-extending DR response became maladaptive during multigenerational DR. Together, our results suggest that the DR response has a low cost and that this phenomenon may have evolved as part of a generalist strategy that extends beyond the benefits of postponing reproduction. KEYWORDS: adaptation; experimental evolution; longevity; nutrition; yeast
  11. Association of Daily Step Count and Step Intensity With Mortality Among US Adults. Saint-Maurice PF, Troiano RP, Bassett DR Jr, Graubard BI, Carlson SA, Shiroma EJ, Fulton JE, Matthews CE. JAMA. 2020 Mar 24;323(12):1151-1160. doi: 10.1001/jama.2020.1382. PMID: 32207799 Abstract IMPORTANCE: It is unclear whether the number of steps per day and the intensity of stepping are associated with lower mortality. OBJECTIVE: Describe the dose-response relationship between step count and intensity and mortality. DESIGN, SETTING, AND PARTICIPANTS: Representative sample of US adults aged at least 40 years in the National Health and Nutrition Examination Survey who wore an accelerometer for up to 7 days ( from 2003-2006). Mortality was ascertained through December 2015. EXPOSURES: Accelerometer-measured number of steps per day and 3 step intensity measures (extended bout cadence, peak 30-minute cadence, and peak 1-minute cadence [steps/min]). Accelerometer data were based on measurements obtained during a 7-day period at baseline. MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular disease (CVD) and cancer mortality. Hazard ratios (HRs), mortality rates, and 95% CIs were estimated using cubic splines and quartile classifications adjusting for age; sex; race/ethnicity; education; diet; smoking status; body mass index; self-reported health; mobility limitations; and diagnoses of diabetes, stroke, heart disease, heart failure, cancer, chronic bronchitis, and emphysema. RESULTS: A total of 4840 participants (mean age, 56.8 years; 2435 [54%] women; 1732 [36%] individuals with obesity) wore accelerometers for a mean of 5.7 days for a mean of 14.4 hours per day. The mean number of steps per day was 9124. There were 1165 deaths over a mean 10.1 years of follow-up, including 406 CVD and 283 cancer deaths. The unadjusted incidence density for all-cause mortality was 76.7 per 1000 person-years (419 deaths) for the 655 individuals who took less than 4000 steps per day; 21.4 per 1000 person-years (488 deaths) for the 1727 individuals who took 4000 to 7999 steps per day; 6.9 per 1000 person-years (176 deaths) for the 1539 individuals who took 8000 to 11 999 steps per day; and 4.8 per 1000 person-years (82 deaths) for the 919 individuals who took at least 12 000 steps per day. Compared with taking 4000 steps per day, taking 8000 steps per day was associated with significantly lower all-cause mortality (HR, 0.49 [95% CI, 0.44-0.55]), as was taking 12 000 steps per day (HR, 0.35 [95% CI, 0.28-0.45]). Unadjusted incidence density for all-cause mortality by peak 30 cadence was 32.9 per 1000 person-years (406 deaths) for the 1080 individuals who took 18.5 to 56.0 steps per minute; 12.6 per 1000 person-years (207 deaths) for the 1153 individuals who took 56.1 to 69.2 steps per minute; 6.8 per 1000 person-years (124 deaths) for the 1074 individuals who took 69.3 to 82.8 steps per minute; and 5.3 per 1000 person-years (108 deaths) for the 1037 individuals who took 82.9 to 149.5 steps per minute. Greater step intensity was not significantly associated with lower mortality after adjustment for total steps per day (eg, highest vs lowest quartile of peak 30 cadence: HR, 0.90 [95% CI, 0.65-1.27]; P value for trend = .34). CONCLUSIONS AND RELEVANCE: Based on a representative sample of US adults, a greater number of daily steps was significantly associated with lower all-cause mortality. There was no significant association between step intensity and mortality after adjusting for total steps per day. Mortality of Japanese Olympic athletes: 1952-2017 cohort study. Takeuchi T, Kitamura Y, Sado J, Hattori S, Kanemura Y, Naito Y, Nakajima K, Okuwaki T, Nakata K, Kawahara T, Sobue T. BMJ Open Sport Exerc Med. 2019 Nov 13;5(1):e000653. doi: 10.1136/bmjsem-2019-000653. eCollection 2019. PMID: 32206340 https://bmjopensem.bmj.com/content/bmjosem/5/1/e000653.full.pdf Abstract AIM: To evaluate mortality among Japanese Olympic athletes compared with the general population and also evaluate their mortality based on total number of Olympics participation and intensity of sports disciplines. METHODS: Information on biography, vital status, date of birth, date of death and latest follow-up date on Japanese Olympians was retrieved from six online databases and compared. Standardised mortality ratio (SMR) was estimated according to observation periods and years from last participation in the Olympics. To further evaluate the association between mortality and total number of Olympics participation/intensity of sports disciplines within the study population, rate ratios (RRs) adjusted by sex, observation period and attained age group were estimated by a Poisson regression model. RESULTS: A total of 3381 Olympians were included in the analysis. The total person years was 94 076.82. The deaths of 153 (4.53%) Olympians were confirmed, and the overall SMR was 0.29 (95% CI, 0.25 to 0.34). SMRs categorised by years from last participation did not differ significantly. Higher mortality was observed among those who participated in the Olympics twice (RR: 1.52; 95% CI, 1.04 to 2.23) and three times or more (RR: 1.87; 95% CI, 1.08 to 3.25) compared with those who participated just once. Compared with combination of low static and low dynamic intensity category, higher mortality was observed in most combinations of middle-intensity or high-intensity categories. CONCLUSION: Japanese Olympians lived longer than the general population. More frequent participation in the Olympics and higher intensity of sports disciplines were associated with higher mortality. KEYWORDS: athlete; epidemiology; longevity; olympics In Contrast to Dietary Restriction, Application of Resveratrol in Mice Does not Alter Mouse Major Urinary Protein Expression. Pallauf K, Günther I, Chin D, Rimbach G. Nutrients. 2020 Mar 19;12(3). pii: E815. doi: 10.3390/nu12030815. PMID: 32204477 Abstract Resveratrol (RSV) supplementation in mice has been discussed as partly mimicking the beneficial effects of dietary restriction (DR). However, data on putative benefits from resveratrol application in mice and other model organisms including humans is contradictory. Mouse major urinary proteins (MUPs) are a family of proteins that are expressed in rodent liver and secreted via urine. Impacting (mating) behavior and pheromone communication, they are severely down-regulated upon DR. We carried out two studies in C57BL/6Rj mice where RSV was either supplemented via diet or injected intraperitoneally for 8 weeks. Contrary to -40% DR, RSV did not decrease total MUP protein expression or Mup (amongst others Mup3, Mup5, Mup6, Mup15, and Mup20) mRNA levels in mouse liver when compared to ad-libitum (AL)-fed controls. Since inhibitory glucocorticoid response elements can be found in Mup promoters, we also measured glucocorticoid receptor (GR) levels in nuclear hepatic extracts. Consistent with differential MUP expression, we observed more nuclear GR in DR mice than in RSV-supplemented and AL control mice with no difference between RSV and AL. These findings point to the notion that, in mice, RSV does not mimic DR in terms of differential MUP expression. KEYWORDS: caloric restriction mimetic; glucocorticoid receptor; longevity Adult weight gain and the risk of cardiovascular disease: a systematic review and dose-response meta-analysis of prospective cohort studies. Jayedi A, Rashidy-Pour A, Soltani S, Zargar MS, Emadi A, Shab-Bidar S. Eur J Clin Nutr. 2020 Mar 18. doi: 10.1038/s41430-020-0610-y. [Epub ahead of print] Review. PMID: 32203236 Abstract We aimed to examine the association of weight gain during adulthood with the risk of cardiovascular disease (CVD) in the general population. We performed a systematic search of PubMed and Scopus, from inception to June 2019. Prospective cohort studies investigating the association of weight gain during adulthood with the risk of CVD were included. The relative risks (RRs) were calculated by using random-effect models. Twenty-three prospective cohort studies with 1,093,337 participants were included. The RRs for a 5-kg increment in body weight were 1.11 (95% CI: 1.04, 1.19; I2 = 80%, n = 11) for CVD mortality, 1.18 (95% CI: 1.04, 1.32; I2 = 90%, n = 8) for coronary heart disease (CHD), 1.08 (95% CI: 1.04, 1.12; I2 = 0%, n = 3) for stroke, 1.18 (95% CI: 1.12, 1.25; I2 = 0%, n = 2) for myocardial infarction and 1.05 (95% CI: 0.86, 1.23; I2 = 80%, n = 2) for heart failure. A dose-response analysis demonstrated that the risk of CVD mortality was unchanged with weight gain of 0-5 kg, and then increased sharply and linearly (P for nonlinearity < 0.001). The analysis of CHD indicated a sharp increase in risk from baseline up to weight gain equal to 25 kg (P for nonlinearity = 0.12). Adult weight gain may be associated with a higher risk of CVD. Measuring weight gain during adulthood may be better than static, cross-sectional assessment of weight because it considers trend over time, and thus, can be used as a supplementary approach to predict CVD. Lemon juice, but not tea, reduces the glycemic response to bread in healthy volunteers: a randomized crossover trial. Freitas D, Boué F, Benallaoua M, Airinei G, Benamouzig R, Le Feunteun S. Eur J Nutr. 2020 Mar 23. doi: 10.1007/s00394-020-02228-x. [Epub ahead of print] PMID: 32201919 Abstract PURPOSE: The inhibition of enzymes that hydrolyze starch during digestion could constitute an opportunity to slow down the release, and ultimately the uptake, of starch-derived glucose. Simple dietary approaches consisting in pairing starch-rich foods with beverages that have the capacity to inhibit such enzymes could be an effective and easily implementable strategy. The objective of this work was to test the impact of black tea and lemon juice on the glycemic response to bread and subsequent energy intake in healthy adults. METHODS: A randomized crossover study was conducted with equal portions of bread (100 g) and 250 ml of water, black tea or lemon juice. Capillary blood glucose concentrations were monitored during 180 min using the finger-prick method. Ad libitum energy intake was assessed 3 h later. RESULTS: Tea had no effect on the glycemic response. Lemon juice significantly lowered the mean blood glucose concentration peak by 30% (p < 0.01) and delayed it more than 35 min (78 vs. 41 min with water, p < 0.0001). None of the tested beverages had an effect on ad libitum energy intake. CONCLUSION: These results are in agreement with previous in vitro studies showing that lowering the pH of a meal can slow down starch digestion through premature inhibition of salivary α-amylase. Furthermore, the effect of lemon juice was similar to what has been repeatedly observed with vinegar and other acidic foods. Including acidic beverages or foods in starchy meals thus appears to be a simple and effective strategy to reduce their glycemic impact. KEYWORDS: Acidity; Glycemic index; Salivary α-amylase; Satiety; Starch; Vinegar Ten-year prospective evaluation of whole-body cancer screening with multiple modalities including [18F]fluorodeoxyglucose positron emission tomography in a healthy population. Nishizawa S, Kojima S, Okada H, Shinke T, Torizuka T, Teramukai S, Fukushima M. Ann Nucl Med. 2020 Mar 21. doi: 10.1007/s12149-020-01456-9. [Epub ahead of print] PMID: 32200511 Abstract PURPOSE: To prospectively evaluate the value of whole-body cancer screening with multiple modalities including FDG-PET in a healthy population. METHODS: The study was conducted in 1197 healthy individuals aged ≥ 35 years at enrollment between August 2003 and July 2004. All participants were scheduled to receive annual whole-body cancer screening five times (screening period) with subsequent long-term follow-up (follow-up period). The endpoints of the study were definitive cancer diagnosis, cancer-related death, and all-cause death. RESULTS: The follow-up rate was 99.8% for the screening period and 96.2% for the follow-up period. Forty-five cancers were confirmed during the screening period (August 2003 to July 2009), and 37 of the 45 were detected by the screening. Fourteen of the 45 were PET positive. Sixteen, 5, 4, 9 and 11 cancers were confirmed after the first, the second, the third, the fourth, and the fifth (took 2 years) screening, respectively. Eight participants died, of whom five died of cancer. The rate of cancer incidence (per 100,000) of 628.7 (95% confidence interval [CI] 445.0-812.4) was significantly high, and the rates of cancer mortality and all-cause mortality of 69.9 (95% CI 8.6-131.1) and 111.8 (95% CI 34.3-189.2), respectively, were significantly low, compared with the corresponding rates of 379.3, 138.2 and 354.2, respectively, in the age-rank- and sex-matched general population. During the follow-up period (August 2009 to July 2013), 37 cancers were confirmed and 30 of the 37 were detected. Seven participants died, of whom three died of cancer. The rate of cancer incidence was 809.6 (95% CI 548.7-1070.5). The rates of cancer mortality and all-cause mortality of 65.6 (95% CI 0-139.9) and 153.2 (95% CI 39.7-266.6), respectively, were significantly low compared with 190.1 and 462.3, respectively, in the general population. CONCLUSION: Cancer detection by PET alone was limited. While the high cancer incidence was attributed to the extensive screening, the low cancer and all-cause mortality may indicate the potential value of this type of cancer screening. Cancer incidence increases with aging and it has been shown that continuous screening may reduce the risk caused by the cancer progression. KEYWORDS: CT; Cancer screening; FDG; MRI; PET; PET/CT
  12. https://www.worldometers.info/coronavirus/#countries says that of those who were shown to be infected and no longer are 14% died.
  13. Dietary intake of choline and phosphatidylcholine and risk of type 2 diabetes in men: The Kuopio Ischaemic Heart Disease Risk Factor Study. Virtanen JK, Tuomainen TP, Voutilainen S. Eur J Nutr. 2020 Mar 20. doi: 10.1007/s00394-020-02223-2. [Epub ahead of print] PMID: 32198672 Abstract PURPOSE: To investigate associations of total dietary choline intake and its major dietary form, phosphatidylcholine, with type 2 diabetes risk. METHODS: We included 2332 men aged 42-60 years at baseline in 1984-1989 from the Kuopio Ischaemic Heart Disease Risk Factor Study in eastern Finland. Dietary intakes were assessed with 4-d food recording at baseline. Type 2 diabetes diagnosis was based on self-administered questionnaires, fasting and 2-h oral glucose tolerance test blood glucose measurements, or by record linkage to national health registries. Multivariable-adjusted Cox proportional hazards regression models were used for statistical analysis. RESULTS: During the mean 19.3-year follow-up, 432 men had type 2 diabetes diagnosis. After multivariable adjustments, those in the highest vs. lowest choline intake quartile had 25% (95% CI 2-43%) lower relative risk (P trend across quartiles = 0.02) and those in the highest vs. lowest phosphatidylcholine quartile had 41% (95% CI 22-55%) lower relative risk (P trend < 0.001) of type 2 diabetes. CONCLUSIONS: Higher choline intake, especially phosphatidylcholine, was associated with lower type 2 diabetes risk among men. KEYWORDS: Choline; Diet; Phosphatidylcholine; Population study; Prospective study; Type 2 diabetes Association of magnesium intake with type 2 diabetes and total stroke: an updated systematic review and meta-analysis. Zhao B, Zeng L, Zhao J, Wu Q, Dong Y, Zou F, Gan L, Wei Y, Zhang W. BMJ Open. 2020 Mar 19;10(3):e032240. doi: 10.1136/bmjopen-2019-032240. PMID: 32198298 Abstract OBJECTIVE: The detailed associations between type 2 diabetes (T2D) and total stroke and magnesium intake as well as the dose-response trend should be updated in a timely manner. DESIGN: Systematic review and meta-analyses. DATA SOURCES: PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov were rigorously searched from inception to 15 March 2019. ELIGIBILITY CRITERIA: Prospective cohort studies investigating these two diseases were included. DATA SYNTHESIS: Relative risk (RR) and 95% CI in random effects models as well as absolute risk (AR) were pooled to calculate the risk of T2D and stroke. Methodological quality was assessed by the Newcastle-Ottawa Scale. RESULTS: Forty-one studies involving 53 cohorts were included. The magnitude of the risk was significantly reduced by 22% for T2D (RR 0.78 (95% CI 0.75 to 0.81); p<0.001; AR reduction 0.120%), 11% for total stroke (RR 0.89 (95% CI 0.83 to 0.94); p<0.001; AR reduction 0.281%) and 12% for ischaemic stroke (RR 0.88 (95% CI 0.81 to 0.95); p=0.001; AR reduction 0.246%) when comparing the highest magnesium intake to the lowest. The inverse association still existed when studies on T2D were adjusted for cereal fibre (RR 0.79; p<0.001) and those on total stroke were adjusted for calcium (RR 0.89; p=0.040). Subgroup analyses suggested that the risk for total and ischaemic stroke was significantly decreased in females, participants with ≥25 mg/m2 body mass index and those with ≥12-year follow-up; the reduced risk in Asians was not as notable as that in North American and European populations. CONCLUSIONS: Magnesium intake has significantly inverse associations with T2D and total stroke in a dose-dependent manner. Feasible magnesium-rich dietary patterns may be highly beneficial for specific populations and could be highlighted in the primary T2D and total stroke prevention strategies disseminated to the public. KEYWORDS: magnesium intake; meta-analysis; stroke; type 2 diabetes Casein- and pea-enriched high-protein diet can take care of the reprotoxic effects of arsenic in male rats. Biswas S, Kumar Mukhopadhyay P. Andrologia. 2020 Mar 20:e13560. doi: 10.1111/and.13560. [Epub ahead of print] PMID: 32196711 Abstract Arsenic toxicity is a significant health problem featured with several incidents of male reproductive dysfunctions. We studied the protective effects of a casein- and pea-enriched formulated high-protein diet (FHPD) on arsenic-mediated testicular dysfunctions in rats. Adult male rats sustained on either a benchmark diet (n = 8 or an isocaloric FHPD (n = 8 were gavaged with arsenic trioxide (3mg/kg body wt/rat/day) for 30 consecutive days. A vehicle-fed group (n = 8 maintained on the standard diet served as control. The arsenic-treated group continued on the standard diet had a significantly reduced testicular and accessory sex organs weights. They exhibited decreased count, motility, viability and disrupted plasma membrane integrity of caudal spermatozoa with a higher incidence of gross morphological anomalies and DNA damage. Attenuated steroidogenic enzyme activities and low serum testosterone level vouched for a compromised state of testicular steroidogenesis. An increased testicular malondialdehyde and protein carbonyl contents coupled with impaired activities of antioxidant enzymes and free radical scavengers mirrored a situation of exacerbated testicular oxidative imbalance and disrupted redox homeostasis. FHPD, by and large, countermanded testicular steroidogenesis and antioxidant defence system and revoked the ill effects of arsenic. We conclude that specific protein-enriched diet may serve as prospective weaponry in encountering the arsenic-threatened testicular functions. KEYWORDS: Arsenic; DNA damage; casein and pea; spermatozoa; ultrastructure Sex-specific metabolic responses to 6 hours fasting during the active phase in young mice. Freire T, Senior AM, Perks R, Pulpitel T, Clark X, Brandon AE, Wahl D, Hatchwell L, Le Couteur DG, Cooney G, Larance M, Simpson SJ, Solon-Biet SM. J Physiol. 2020 Mar 21. doi: 10.1113/JP278806. [Epub ahead of print] PMID: 32198893 Abstract KEY POINTS: Night time/active phase food restriction for 6 hr impaired glucose intolerance in young male and female mice. Females displayed increased capacity for lipogenesis and triglyceride storage in response to a short daily fast. Females had lower fasting insulin levels and an increased potential for utilizing fat for energy through β-oxidation compared to males. The need for the inclusion of both sexes, and the treatment of sex as an independent variable, is emphasized within the context of this fasting regime. ABSTRACT: There is growing interest in understanding the mechanistic significance and benefits of fasting physiology in combating obesity. Increasing the fasting phase of a normal day can promote restoration and repair mechanisms that occur during the post-absorptive period. Most studies exploring the effect of restricting food access on mitigating obesity have done so with a large bias towards the use of male mice. Here, we disentangle the roles of sex, food intake and food withdrawal in the response to a short-term daily fasting intervention, where food was removed for six hours in the dark/active phase of young, 8-week old mice. We showed that the removal of food during the dark phase impaired glucose tolerance in males and females, possibly due to the circadian disruption induced by this feeding protocol. Although both sexes demonstrated similar patterns of food intake, body composition and various metabolic markers, there were clear sex differences in the magnitude and extent of these responses. While females displayed enhanced capacity for lipogenesis and triglyceride storage, they also had low fasting insulin levels and an increased potential for utilizing available energy sources such as fat for energy through β-oxidation. Our results highlight the intrinsic biological and metabolic disparities between male and female mice, emphasizing the growing need for the inclusion of both sexes in scientific research. Furthermore, our results illustrate sex-specific metabolic pathways that regulate lipogenesis, obesity and overall metabolic health. This article is protected by copyright. All rights reserved. KEYWORDS: circadian rhythm; food timing; lipogenesis; obesity; sex effects; short daily fasting Relationship Between Dietary Magnesium Intake and Incident Heart Failure Among Older Women: The WHI. Wu WC, Huang M, Taveira TH, Roberts MB, Martin LW, Wellenius GA, Johnson KC, Manson JE, Liu S, Eaton CB. J Am Heart Assoc. 2020 Apr 7;9(7):e013570. doi: 10.1161/JAHA.119.013570. Epub 2020 Mar 20. PMID: 32192409 Abstract Background Women represent a large proportion of the growing heart failure (HF) epidemic, yet data are lacking regarding optimal dietary and lifestyle prevention strategies for them. Specifically, the association between magnesium intake and HF in a multiracial cohort of women is uncertain. Methods and Results We included 97 725 postmenopausal women from the WHI (Women's Health Initiative) observational studies and placebo arms of the hormone trial. Magnesium intake was measured at baseline by a 122-item validated food-frequency questionnaire and stratified into quartiles based on diet only, total intake (diet with supplements), and residual intake (calibration by total energy). Incident hospitalized HF (2153 events, median follow-up 8.1 years) was adjudicated by medical record abstraction. In Cox proportional hazards models, we evaluated the association between magnesium intake and HF adjusting for potential confounders. Analyses were repeated on a subcohort (n=18 745; median-follow-up, 13.2 years) for whom HF cases were subclassified into preserved ejection fraction (526 events), reduced ejection fraction (291 events) or unknown (168 events). Most women were white (85%) with a mean age of 63. Compared with the highest quartile of magnesium intake, women in the lowest quartile had an increased risk of incident HF, with adjusted hazard ratios of 1.32 (95% CI, 1.02-1.71) for diet only (P trend=0.03), 1.26 (95% CI, 1.03-1.56) for total intake, and 1.31 (95% CI, 1.02-1.67) for residual intake. Results did not significantly vary by race. Subcohort analyses showed low residual magnesium intake was associated with HF with reduced ejection fraction (hazard ratio, 1.81, lowest versus highest quartile; 95% CI, 1.08-3.05) but not HF with preserved ejection fraction. Conclusions Low magnesium intake in a multiracial cohort of postmenopausal women was associated with a higher risk of incident HF, especially HF with reduced ejection fraction. KEYWORDS: heart failure with preserved ejection fraction; heart failure with reduced ejection fraction; residual method; total magnesium Potato consumption is associated with total and cause-specific mortality: a population-based cohort study and pooling of prospective studies with 98,569 participants. Mazidi M, Katsiki N, Mikhailidis DP, Pella D, Banach M. Arch Med Sci. 2020 Feb 11;16(2):260-272. doi: 10.5114/aoms.2020.92890. eCollection 2020. PMID: 32190135 Abstract INTRODUCTION: The long-term effect of potato consumption on mortality and cardiovascular (CV) and cardiometabolic risk factors is still largely unknown. Using the National Health and Nutrition Examination Surveys (NHANES) 1999-2010, we evaluted the long-term impact of potato intake on total and cause-specific (cardiovascular disease (CVD), cerebrovascular disease and cancer) mortality, and the results were next validated in a systematic review and meta-analysis of cohort studies investigating pooled associations of potato consumption with all-cause and cause-specific death. MATERIAL AND METHODS: Vital status up to December 31, 2011 was ascertained in NHANES. Cox proportional hazards were applied to determine the hazard ratios (HRs) and 95% confidence intervals (95% CI) of mortality for each quartile of the potato intake, with the lowest quartile (Q1 - with the lowest intake) used as a reference. In the meta-analysis we used adjusted Cox regression to determine the risk ratio (RR) and 95% CI, as well as random effects models and generic inverse variance methods to synthesize quantitative and pooled data, followed by a leave-one-out method for sensitivity analysis. RESULTS: Among 24,856 participants included, 3433 deaths occurred during the mean follow-up of 6.4 years. In multivariate adjusted models, total (42%), CVD (65%), cerebrovascular (26%) and cancer (52%) mortality risk was greater in individuals with higher potato consumption than those with the lowest intake (p < 0.001 for all comparisons). However, this link disappeared after adjustment for confounding factors. Results from pooling current prospective studies revealed a non-significant association between total (RR = 1.25, 0.98-1.60, p = 0.066), CVD (RR = 0.99, 0.90-1.08, p = 0.845) and stroke mortality (RR = 0.94, 0.85-1.03, p = 0.214) with potato consumption. Individuals with a higher potato intake had a less favorable profile of cardiometabolic factors, including greater waist circumference (97.2 vs. 99.5 cm, p < 0.001) and a less favorable profile of systolic and diastolic blood pressure, levels of triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C) and TG/HDL-C ratio (p < 0.001 for all comparisons). CONCLUSIONS: Our results revealed no significant effects of potato intake on long-term mortality rates, whereas higher potato consumption was adversely related to cardiometabolic risk factors. These findings should be taken into consideration for public health strategies, establishing the position for potatoes in the food pyramid. KEYWORDS: cardiometabolic; cardiovascular disease; meta-analysis; mortality; potato; stroke Hepatic de novo lipogenesis is suppressed and fat oxidation is increased by omega-3 fatty acids at the expense of glucose metabolism. Green CJ, Pramfalk C, Charlton CA, Gunn PJ, Cornfield T, Pavlides M, Karpe F, Hodson L. BMJ Open Diabetes Res Care. 2020 Mar;8(1). pii: e000871. doi: 10.1136/bmjdrc-2019-000871. PMID: 32188593 Free Article Abstract OBJECTIVE: Increased hepatic de novo lipogenesis (DNL) is suggested to be an underlying cause in the development of nonalcoholic fatty liver disease and/or insulin resistance. It is suggested that omega-3 fatty acids (FA) lower hepatic DNL. We investigated the effects of omega-3 FA supplementation on hepatic DNL and FA oxidation using a combination of human in vivo and in vitro studies. RESEARCH DESIGN AND METHODS: Thirty-eight healthy men were randomized to take either an omega-3 supplement (4 g/day eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) as ethyl esters) or placebo (4 g/day olive oil) and fasting measurements were made at baseline and 8 weeks. The metabolic effects of omega-3 FAs on intrahepatocellular triacylglycerol (IHTAG) content, hepatic DNL and FA oxidation were investigated using metabolic substrates labeled with stable-isotope tracers. In vitro studies, using a human liver cell-line was undertaken to gain insight into the intrahepatocellular effects of omega-3 FAs. RESULTS: Fasting plasma TAG concentrations significantly decreased in the omega-3 group and remained unchanged in the placebo group. Eight weeks of omega-3 supplementation significantly decreased IHTAG, fasting and postprandial hepatic DNL while significantly increasing dietary FA oxidation and fasting and postprandial plasma glucose concentrations. In vitro studies supported the in vivo findings of omega-3 FAs (EPA+DHA) decreasing intracellular TAG through a shift in cellular metabolism away from FA esterification toward oxidation. CONCLUSIONS: Omega-3 supplementation had a potent effect on decreasing hepatic DNL and increasing FA oxidation and plasma glucose concentrations. Attenuation of hepatic DNL may be considered advantageous; however, consideration is required as to what the potential excess of nonlipid substrates (eg, glucose) will have on intrahepatic and extrahepatic metabolic pathways. KEYWORDS: de novo lipogenesis; fatty acid oxidation; liver fat; omega-3 fatty acids Associations of fat and carbohydrate intake with cardiovascular disease and mortality: prospective cohort study of UK Biobank participants. Ho FK, Gray SR, Welsh P, Petermann-Rocha F, Foster H, Waddell H, Anderson J, Lyall D, Sattar N, Gill JMR, Mathers JC, Pell JP, Celis-Morales C. BMJ. 2020 Mar 18;368:m688. doi: 10.1136/bmj.m688. PMID: 32188587 Free Article https://www.bmj.com/content/bmj/368/bmj.m688.full.pdf Abstract OBJECTIVE: To investigate the association of macronutrient intake with all cause mortality and cardiovascular disease (CVD), and the implications for dietary advice. DESIGN: Prospective population based study. SETTING: UK Biobank. PARTICIPANTS: 195 658 of the 502 536 participants in UK Biobank completed at least one dietary questionnaire and were included in the analyses. Diet was assessed using Oxford WebQ, a web based 24 hour recall questionnaire, and nutrient intakes were estimated using standard methodology. Cox proportional models with penalised cubic splines were used to study non-linear associations. MAIN OUTCOME MEASURES: All cause mortality and incidence of CVD. RESULTS: 4780 (2.4%) participants died over a mean 10.6 (range 9.4-13.9) years of follow-up, and 948 (0.5%) and 9776 (5.0%) experienced fatal and non-fatal CVD events, respectively, over a mean 9.7 (range 8.5-13.0) years of follow-up. Non-linear associations were found for many macronutrients. Carbohydrate intake showed a non-linear association with mortality; no association at 20-50% of total energy intake but a positive association at 50-70% of energy intake (3.14 v 2.75 per 1000 person years, average hazard ratio 1.14, 95% confidence interval 1.03 to 1.28 (60-70% v 50% of energy)). A similar pattern was observed for sugar but not for starch or fibre. A higher intake of monounsaturated fat (2.94 v 3.50 per 1000 person years, average hazard ratio 0.58, 0.51 to 0.66 (20-25% v 5% of energy)) and lower intake of polyunsaturated fat (2.66 v 3.04 per 1000 person years, 0.78, 0.75 to 0.81 (5-7% v 12% of energy)) and saturated fat (2.66 v 3.59 per 1000 person years, 0.67, 0.62 to 0.73 (5-10% v 20% of energy)) were associated with a lower risk of mortality. A dietary risk matrix was developed to illustrate how dietary advice can be given based on current intake. CONCLUSION: Many associations between macronutrient intake and health outcomes are non-linear. Thus dietary advice could be tailored to current intake. Dietary guidelines on macronutrients (eg, carbohydrate) should also take account of differential associations of its components (eg, sugar and starch). Significant reduction in the LDL cholesterol increases the risk of intracerebral hemorrhage: a systematic review and meta-analysis of 33 randomized controlled trials. Cheng Y, Qiao L, Jiang Z, Dong X, Feng H, Gui Q, Lu Y, Liang Y. Am J Transl Res. 2020 Feb 15;12(2):463-477. eCollection 2020. PMID: 32194896 Abstract The dose-dependent pleiotropic effects of statin therapy may have unwanted side effects such as increasing the risk of intracerebral hemorrhage (ICH). The relationships among statin therapy, LDL-cholesterol levels, and ICH risk remain controversial. Here, we conduct a systematic review and meta-analysis of dose-dependent statin therapy and ICH risk. Eligible articles were identified by searching MEDLINE from inception up to December 1, 2018. Reference lists of previous meta-analyses were manually searched to retrieve all relevant publications. Statin doses were allocated into one of two groups according to the observed reduction of LDL cholesterol: doses that lowered LDL-cholesterol levels ≥35% were regarded as high-dose statin therapy, whereas those that lowered LDL-cholesterol levels <35% were regarded as low-dose statin therapy. We retrieved 33 studies involving 203,305 subjects. The pooled analysis indicated that high-dose statin treatment significantly increased the risk of ICH [relative risk (RR), 1.35; 95% confidence interval (CI), 1.08-1.68] and reduced the risk of all stroke (RR, 0.85; 95% CI, 0.78-0.92), ischemic stroke (RR, 0.79; 95% CI, 0.72-0.87), and all-cause mortality (RR, 0.94; 95% CI, 0.90-0.98). The analyses did not detect any association between low-dose statin treatment and ICH (RR, 1.05; 95% CI, 0.88-1.25). Low-dose statin therapy significantly reduced the incidence of all stroke (RR, 0.84; 95% CI, 0.79-0.89), ischemic stroke (RR, 0.81; 95% CI, 0.76-0.86), and all-cause mortality (RR, 0.94; 95% CI, 0.92-0.97). Our data indicate that low-dose statin therapy is a safe and effective ICH treatment, whereas high-dose statin therapy is associated with increased ICH risk. Hence, our meta-analysis suggests that the dose-dependent pleiotropic effects of statin therapy are related to the measured reduction in LDL cholesterol. KEYWORDS: High-dose statin therapy; intracerebral hemorrhage; low-dose statin therapy; meta-analysis Effects of dairy products on bone mineral density in healthy postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Shi Y, Zhan Y, Chen Y, Jiang Y. Arch Osteoporos. 2020 Mar 18;15(1):48. doi: 10.1007/s11657-020-0694-y. Review. PMID: 32185512 Abstract PURPOSE: To investigate the effects of dairy products on bone mineral density (BMD) in healthy postmenopausal women. METHODS: The EMBASE, Cochrane Library, Medline, and Web of Science databases were systematically searched for relevant studies. The pooled standardized mean difference (SMD) with its 95% confidence interval (CI) was used as the effect size. Subgroup analysis and Begg's test were conducted. RESULTS: Six studies with a total of 618 participants were included in the meta-analysis. Milk was the main dairy product used in the trials. There was a significant association between dairy product consumption and BMD of the lumbar spine (SMD 0.21, 95% CI 0.05-0.37, P = 0.009), femoral neck (SMD 0.36, 95% CI 0.19-0.53, P < 0.001), total hip (SMD 0.37, 95% CI 0.20-0.55, P < 0.001), and total body (SMD 0.58, 95% CI 0.39-0.77, P < 0.001). Subgroup analysis suggested that there was a positive effect of dairy product consumption on the BMD of the total hip starting from 12 months and the femoral neck starting from 18 months. There was also a positive association with the BMD in the four sites in people living in low-calcium intake countries. CONCLUSION: This meta-analysis provides evidence that dairy products can increase BMD in healthy postmenopausal women. Dairy product consumption should be considered an effective public health measure to prevent osteoporosis in postmenopausal women. KEYWORDS: Bone mineral density; Dairy products; Osteoporosis; Postmenopausal women Beneficial impact of exercise on bone mass in individuals under calorie restriction: a systematic review and Meta-analysis of randomized clinical trials. Yarizadeh H, Asadi S, Baharlooi H, Setayesh L, Kakavandi NR, Hambly C, Djafarian K, Mirzaei K. Crit Rev Food Sci Nutr. 2020 Mar 17:1-13. doi: 10.1080/10408398.2020.1739620. [Epub ahead of print] PMID: 32180431 https://sci-hub.tw/10.1080/10408398.2020.1739620 Abstract Background: A major therapeutic goal in weight management should be total body fat reduction whereas as preserving lean body mass and bone mass density. It is uncertain if an exercise program reduces the adverse effects of calorie restriction-induced weight loss in adults.Objective: The aim of the present study was to evaluate the differences in bone mass between adults who enrolled in a calorie restriction or an exercise-calorie restriction induced weight loss program.Data sources: Both PubMed and Scopus libraries were searched up to February 2020.Methods: Systematic reviews and a meta-analysis were carried out of randomized clinical trials (published to February 2020) on differences in bone mineral density and content (BMD and BMC) of adults who lost weight by calorie restriction alone (CR) or exercise-calorie restriction (CR-E). The study quality was calculated using the Cochrane scoring system. Retrieved data were pooled when weight mean differences (WMDs) were computed between two groups for BMD and BMC at various sites of the body.Results: Thirteen studies, with a total of 852 participants were included. Available evidence found significantly higher BMD at the hip (WMD: 0.03 g/cm2, 95%CI: 0.01 to 0.04, p < 0.001) and femoral neck WMD: 0.03 g/cm2, 95%CI: 0.01 to 0.05, p < 0.001) and total body BMC (WMD: 0.13 kg/cm2, 95%CI: -0.10 to 0.36, p < 0.001) in the CR-E compared to the CR weight loss group. In contrast, all changes in total body BMD (WMD: 0.00 g/cm2, 95%CI: -0.01 to 0.02, p = 0.57) and lumbar spine BMD (WMD: 0.00 g/cm2, 95%CI: -0.01 to 0.01, p = 0.89) were not statistically significant.Limitations: Little evidence was available for different sexes separately. Most individuals were postmenopausal females and no subgroup analysis could be conducted based on menopausal status.Conclusion: This study suggests that physical training can preserve and even significantly increase the bone mass of the hip and femoral neck during weight reduction. Of note, various exercise modalities affected BMD at different sites. Similar results were not found for lumbar spine and total body BMD. KEYWORDS: Exercise; bone; calorie restriction; meta-analysis Time-of-Day-Dependent Physiological Responses to Meal and Exercise. Aoyama S, Shibata S. Front Nutr. 2020 Feb 28;7:18. doi: 10.3389/fnut.2020.00018. eCollection 2020. Review. PMID: 32181258 Abstract The mammalian circadian clock drives the temporal coordination in cellular homeostasis and it leads the day-night fluctuation of physiological functions, such as sleep/wake cycle, hormonal secretion, and body temperature. The mammalian circadian clock system in the body is classified hierarchically into two classes, the central clock in the suprachiasmatic nucleus (SCN) of the hypothalamus and the peripheral clocks in peripheral tissues such as the intestine and liver, as well as other brain areas outside the SCN. The circadian rhythm of various tissue-specific functions is mainly controlled by each peripheral clock and partially by the central clock as well. The digestive, absorptive, and metabolic capacities of nutrients also show the day-night variations in several peripheral tissues such as small intestine and liver. It is therefore indicated that the bioavailability or metabolic capacity of nutrients depends on the time of day. In fact, the postprandial response of blood triacylglycerol to a specific diet and glucose tolerance exhibit clear time-of-day effects. Meal frequency and distribution within a day are highly related to metabolic functions, and optimal time-restricted feeding has the potential to prevent several metabolic dysfunctions. In this review, we summarize the time-of-day-dependent postprandial response of macronutrients to each meal and the involvement of circadian clock system in the time-of-day effect. Furthermore, the chronic beneficial and adverse effects of meal time and eating pattern on metabolism and its related diseases are discussed. Finally, we discuss the timing-dependent effects of exercise on the day-night variation of exercise performance and therapeutic potential of time-controlled-exercise for promoting general health.
  14. The association of outdoor temperature with blood pressure, and its influence on future cardio-cerebrovascular disease risk in cold areas. Yu B, Jin S, Wang C, Yan S, Zhou X, Cui X, Tang Z, Luan Q, Guo Y, Bian Z, Li L, Chen Z, Na L. J Hypertens. 2020 Mar 13. doi: 10.1097/HJH.0000000000002387. [Epub ahead of print] PMID: 32195817 Abstract OBJECTIVES: To explore whether lower outdoor temperature increases cardio-cerebrovascular disease risk through regulating blood pressure and whether indoor heating in winter is beneficial to prevent cardio-cerebrovascular disease in cold areas. METHODS: We analyzed the data of 38 589 participants in Harbin from the China Kadoorie Biobank (CKB) during 2004-2008, with an average of 7.14-year follow-up. Linear regression analysis was performed to estimate the relationship between outdoor temperature and blood pressure. Cox regression analysis and logistic regression analysis were used to analyze the association of blood pressure with cardio-cerebrovascular event risk. Mediation analysis was performed to explore the role of blood pressure in the association between outdoor temperature and cardio-cerebrovascular events risk. RESULTS: There was an increase of 6.7 mmHg in SBP and 2.1 mmHg in DBP for each 10 °C decrease in outdoor temperature when outdoor temperature was higher than 5 °C. There was an inverse association between outdoor temperature and cardio-cerebrovascular event morbidity. The increases in blood pressure and cardio-cerebrovascular event morbidity were attenuated in months when central heating was fully provided. Participants with hypertension have higher risks of cardio-cerebrovascular disease (hazard ratio 1.347; 95% CI 1.281--1.415), CVD (hazard ratio 1.347; 95% CI 1.282--1.416), MACE (hazard ratio 1.670; 95% CI 1.560--1.788) and stroke (hazard ratio 1.683; 95% CI 1.571--1.803). Mediation analysis demonstrated that the association between outdoor temperature and cardio-cerebrovascular events risk was potentially mediated by blood pressure. CONCLUSION: Temperature-driven blood pressure potentially mediates the association between outdoor temperature and cardio-cerebrovascular events risk. Indoor heating in winter is probably beneficial to cardio-cerebrovascular disease prevention by inhibition of blood pressure increase.
  15. AlPater

    Al's CR updates

    Effects of aging and life-long moderate calorie restriction on IL-15 signaling in the rat white adipose tissue. Giovannini S, Carter CS, Leeuwenburgh C, Flex A, Biscetti F, Morgan D, Laudisio A, Coraci D, Maccauro G, Zuccalà G, Caliandro P, Bernabei R, Marzetti E. Eur Rev Med Pharmacol Sci. 2020 Mar;24(5):2738-2749. doi: 10.26355/eurrev_202003_20547. PMID: 32196625 Abstract OBJECTIVE: Phosphorylation of insulin receptor substrate (IRS) 1 by tumor necrosis factor alpha (TNF-α) has been implicated as a factor contributing to insulin resistance. Administration of IL-15 reduces adipose tissue deposition in young rats and stimulates secretion of adiponectin, an insulin sensitizing hormone that inhibits the production and activity of TNF-α. We aimed at investigating the effects of age life-long moderate calorie restriction (CR) on IL-15 and TNF-α signaling in rat white adipose tissue (WAT). MATERIALS AND METHODS: Thirty-six 8-month-old, 18-month-old, and 29-month-old male Fischer344´Brown Norway F1 rats (6 per group) were either fed ad libitum (AL) or calorie restricted by 40%. The serum levels of IL-15 and IL-15 receptor α-chain (IL-15Rα) were increased by CR controls regardless of age. An opposite pattern was detected in WAT. In addition, CR reduced gene expression of TNF-α and cytosolic IRS1 serine phosphorylation in WAT, independently from age. RESULTS: IL-15 signaling in WAT is increased over the course of aging in AL rats compared with CR rodents. Protein levels of IL-15Rα are greater in WAT of AL than in CR rats independently from age. This adaptation was paralleled by increased IRS1 phosphorylation through TNF-α-mediated insulin resistance. Adiponectin decreased at old age in AL rats, while no changes were evident in CR rats across age groups. CONCLUSIONS: IL-15 signaling could therefore represent a potential target for interventions to counteract metabolic alterations and the deterioration of body composition during aging.