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  1. Sleep Duration and the Risk of Dementia: A Systematic Review and Meta-analysis of Prospective Cohort Studies. Fan L, Xu W, Cai Y, Hu Y, Wu C. J Am Med Dir Assoc. 2019 Oct 8. pii: S1525-8610(19)30495-5. doi: 10.1016/j.jamda.2019.06.009. [Epub ahead of print] Review. PMID: 31604673 Abstract OBJECTIVE: Epidemiologic studies have reported inconsistent findings about the association between sleep duration and the risk of dementia. We aimed to clarify this association by method of meta-analysis. DESIGN: Systematic review and meta-analysis of prospective cohort studies. SETTING AND PARTICIPANTS: Community or clinical settings. Participants included patients with dementia or Alzheimer's disease and the general population. MEASURES: We systematically searched the PubMed, EMBASE, and Web of Science for prospective cohort studies investigating the association between sleep duration and all-cause dementia or Alzheimer's disease (AD). Generic inverse-variance method was used to combine the outcomes with a random effects model for the association between sleep duration (short or long vs normal) and all-cause dementia or AD. RESULTS: We identified 7 studies for all-cause dementia and 6 studies for AD. Pooled analyses showed that long sleep duration was associated with a 77% increased risk of all-cause dementia [hazard ratio (HR) = 1.77, 95% confidence interval (CI) = 1.32-2.37] and a 63% increased risk of AD (HR = 1.63, 95% CI = 1.24-2.13). Short sleep duration was not statistically associated with an increased risk of all-cause dementia (HR = 1.20, 95% CI = 0.91-1.59) or AD (HR = 1.18, 95% CI = 0.91-1.54). CONCLUSIONS AND IMPLICATIONS: Only long sleep duration is significantly associated with an increased risk of all-dementia and AD. Future studies are needed to better understand the mechanisms underlying this association. KEYWORDS: Alzheimer's disease; Sleep duration; all-cause dementia; meta-analysis
  2. Fermented Milk Products and Bone Health in Postmenopausal Women: A Systematic Review of Randomized Controlled Trials, Prospective Cohorts, and Case-Control Studies. Ong AM, Kang K, Weiler HA, Morin SN. Adv Nutr. 2019 Oct 11. pii: nmz108. doi: 10.1093/advances/nmz108. [Epub ahead of print] PMID: 31603185 Abstract Milk and milk product consumption is positively associated with bone mineral density (BMD). Emerging evidence suggests that fermented milk products (FMPs) may have specific beneficial effects on skeletal health. We conducted a systematic review and meta-analysis to assess the effect of FMPs on bone health indicators in postmenopausal women given their increased risk for osteoporosis and fragility fractures. Electronic databases were searched for randomized controlled trials (RCTs) and prospective cohort and case-control studies that examined the relation between FMPs and bone health outcomes (fracture incidence, BMD, BMD T-score, and percentage change in bone turnover markers) in postmenopausal women. Two reviewers independently conducted abstract and full-text screenings and data extractions. Risk of bias was assessed using the RoB 2.0 tool and the Newcastle-Ottawa scale for interventional and observational studies. Pooled RRs were obtained using a random-effects model by the DerSimonian-Laird method. Three RCTs, 3 prospective cohorts, and 3 case-control studies met the inclusion criteria. Results of the meta-analysis of 3 cohort studies (n = 102,819) suggest that higher yogurt consumption was associated with reduced hip fracture risk (pooled RR: 0.76; 95% CI: 0.63, 0.92, I2 = 29%), but no difference in hip fracture risk was found between higher and lower cheese consumption (pooled RR: 0.89; 95% CI: 0.73, 1.10, I2 = 0%). Case-control studies revealed that cheese intake had either a null or a protective effect against osteoporosis (BMD T-score ≤-2.5). Daily yogurt or cheese intervention (<2 mo) decreased bone resorption marker concentrations, but had no effect on bone formation markers. In postmenopausal women, of the FMPs studied, only greater yogurt consumption was associated with a reduced risk of hip fracture compared with low or no intake. Daily cheese intake may be associated with higher BMD T-scores, but evidence was limited. Additional and longer-term trials examining these relations are warranted. KEYWORDS: bone mineral density; bone turnover markers; cheese; fermented milk products; fractures; postmenopausal women; yogurt Association of dietary lipid intake with low-density lipoprotein cholesterol levels: analysis of two independent population-based studies. Kwon YJ, Lee HS, Chang HJ, Koh SB, Lee JW. Eur J Nutr. 2019 Oct 10. doi: 10.1007/s00394-019-02104-3. [Epub ahead of print] PMID: 31602495 Slow walking at 45 'a sign of faster ageing' By Philippa Roxby Health reporter, BBC News 12 October 2019 https://www.bbc.com/news/health-50015982 >>>>>>>>>>>>>> October 11, 2019 Association of Neurocognitive and Physical Function With Gait Speed in Midlife Line Jee Hartmann Rasmussen, PhD; Avshalom Caspi, PhD; Antony Ambler, MSc; Jonathan M. Broadbent, PhD; Harvey J. Cohen, MD; Tracy d’Arbeloff, BA; Maxwell Elliott, BS; Robert J. Hancox, MD; HonaLee Harrington, BA; Sean Hogan, BA; Renate Houts, PhD; David Ireland, PhD; Annchen R. Knodt, MSc; Kim Meredith-Jones, PhD; Miriam C. Morey, PhD; Lynda Morrison, BSc; Richie Poulton, PhD; Sandhya Ramrakha, PhD; Leah Richmond-Rakerd, PhD; Maria L. Sison, BS; Kate Sneddon, PhD; W. Murray Thomson, PhD; Ahmad R. Hariri, PhD; Terrie E. Moffitt, PhD open access JAMA Netw Open. 2019; 2(10):e1913123. doi: 10.1001/jamanetworkopen.2019.13123 This 5-decade cohort study of a New Zealand population examines whether slow gait speed in middle age is associated with accelerated biological aging, as well as poor neurocognitive functioning in childhood and cognitive decline from childhood to middle age. https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2752818 Key Points Question Is gait speed measured at age 45 years associated with accelerated biological aging, neurocognitive function, and cognitive decline? Findings In this 5-decade cohort study of 904 participants in New Zealand, physical and biological indicators of accelerated aging, including compromised brain integrity (eg, reduced brain volume and cortical thickness), were associated with slow gait measured at age 45 years. Lifelong compromised brain health—including poor neurocognitive functioning as early as age 3 years and childhood-to-adulthood decline in cognitive functioning—was associated with slower gait at midlife. Meaning Gait speed at midlife may be a summary index of lifelong aging with possible origins in childhood central nervous system deficits. Abstract Importance Gait speed is a well-known indicator of risk of functional decline and mortality in older adults, but little is known about the factors associated with gait speed earlier in life. Objectives To test the hypothesis that slow gait speed reflects accelerated biological aging at midlife, as well as poor neurocognitive functioning in childhood and cognitive decline from childhood to midlife. Design, Setting, and Participants This cohort study uses data from the Dunedin Multidisciplinary Health and Development Study, a population-based study of a representative 1972 to 1973 birth cohort in New Zealand that observed participants to age 45 years (until April 2019). Data analysis was performed from April to June 2019. Exposures Childhood neurocognitive functions and accelerated aging, brain structure, and concurrent physical and cognitive functions in adulthood. Main Outcomes and Measures Gait speed at age 45 years, measured under 3 walking conditions: usual, dual task, and maximum gait speeds. Results Of the 1037 original participants (91% of eligible births; 535 [51.6%] male), 997 were alive at age 45 years, of whom 904 (90.7%) had gait speed measured (455 [50.3%] male; 93% white). The mean (SD) gait speeds were 1.30 (0.17) m/s for usual gait, 1.16 (0.23) m/s for dual task gait, and 1.99 (0.29) m/s for maximum gait. Adults with more physical limitations (standardized regression coefficient [β], −0.27; 95% CI, −0.34 to −0.21; P < .001), poorer physical functions (ie, weak grip strength [β, 0.36; 95% CI, 0.25 to 0.46], poor balance [β, 0.28; 95% CI, 0.21 to 0.34], poor visual-motor coordination [β, 0.24; 95% CI, 0.17 to 0.30], and poor performance on the chair-stand [β, 0.34; 95% CI, 0.27 to 0.40] or 2-minute step tests [β, 0.33; 95% CI, 0.27 to 0.39]; all P < .001), accelerated biological aging across multiple organ systems (β, −0.33; 95% CI, −0.40 to −0.27; P < .001), older facial appearance (β, −0.25; 95% CI, −0.31 to −0.18; P < .001), smaller brain volume (β, 0.15; 95% CI, 0.06 to 0.23; P < .001), more cortical thinning (β, 0.09; 95% CI, 0.02 to 0.16; P = .01), smaller cortical surface area (β, 0.13; 95% CI, 0.04 to 0.21; P = .003), and more white matter hyperintensities (β, −0.09; 95% CI, −0.15 to −0.02; P = .01) had slower gait speed. Participants with lower IQ in midlife (β, 0.38; 95% CI, 0.32 to 0.44; P < .001) and participants who exhibited cognitive decline from childhood to adulthood (β, 0.10; 95% CI, 0.04 to 0.17; P < .001) had slower gait at age 45 years. Those with poor neurocognitive functioning as early as age 3 years had slower gait in midlife (β, 0.26; 95% CI, 0.20 to 0.32; P < .001). Conclusions and Relevance Adults’ gait speed is associated with more than geriatric functional status; it is also associated with midlife aging and lifelong brain health.
  3. AlPater

    Al's CR updates

    Impact of energy turnover on fat balance in healthy young men during energy balance, caloric restriction and overfeeding. Nas A, Büsing F, Hägele FA, Hasler M, Müller MJ, Bosy-Westphal A. Br J Nutr. 2019 Oct 11:1-27. doi: 10.1017/S0007114519002551. [Epub ahead of print] PMID: 31601285 Abstract Body weight control is thought to be improved when physical activity and energy intake are both high (high energy turnover). The aim of this study was to investigate the short-term impact of energy turnover (ET) on fat balance during zero energy balance, caloric restriction and overfeeding. In a randomized crossover study, 9 healthy men (BMI: 23.0 ±2.1 kg/m2, 26.6 ±3.5 y) passed 3x3 days in a metabolic chamber: 3 levels of ET (low, medium and high; physical activity level = 1.3-1.4, 1.5-1.6 and 1.7-1.8) were performed at zero energy balance (EB), caloric restriction (CR), and overfeeding (OF) (100%, 75%, 125% of individual energy requirement). Different levels of ET were obtained by walking (4 km/h) on a treadmill (0, 165, 330 min). 24-h macronutrient oxidation and relative macronutrient balance (oxidation relative to intake) were calculated and free fatty acids, 24-h insulin and catecholamine secretion were analyzed as determinants of fat oxidation. During EB and OF, 24-h fat oxidation increased with higher ET. This resulted in a higher relative fat balance at medium ET (EB: +17%, OF: +14%) and high ET (EB: +23%, OF: +17%) compared to low ET (all p<0.05). In contrast, CR led to a stimulation of 24-h fat oxidation irrespective of ET (no differences in relative fat balance between ET levels, p>0.05). In conclusion, under highly controlled conditions a higher energy turnover improved relative fat balance in young healthy men during overfeeding and energy balance compared to a sedentary state. KEYWORDS: ClinicalTrials.gov as NCT03361566; energy expenditure; energy turnover; fat oxidation; metabolic chamber; physical activity The Effectiveness of Intermittent Fasting to Reduce Body Mass Index and Glucose Metabolism: A Systematic Review and Meta-Analysis. Cho Y, Hong N, Kim KW, Cho SJ, Lee M, Lee YH, Lee YH, Kang ES, Cha BS, Lee BW. J Clin Med. 2019 Oct 9;8(10). pii: E1645. doi: 10.3390/jcm8101645. PMID: 31601019 https://www.mdpi.com/2077-0383/8/10/1645/htm Abstract The effects of an intermittent fasting diet (IFD) in the general population are still controversial. In this study, we aimed to systematically evaluate the effectiveness of an IFD to reduce body mass index and glucose metabolism in the general population without diabetes mellitus. Cochrane, PubMed, and Embase databases were searched to identify randomized controlled trials and controlled clinical trials that compared an IFD with a regular diet or a continuous calorie restriction diet. The effectiveness of an IFD was estimated by the weighted mean difference (WMD) for several variables associated with glucometabolic parameters including body mass index (BMI) and fasting glucose. The pooled mean differences of outcomes were calculated using a random effects model. From 2814 studies identified through a literature search, we finally selected 12 articles (545 participants). Compared with a control diet, an IFD was associated with a significant decline in BMI (WMD, -0.75 kg/m2; 95% CI, -1.44 to -0.06), fasting glucose level (WMD, -4.16 mg/dL; 95% CI, -6.92 to -1.40), and homeostatic model assessment of insulin resistance (WMD, -0.54; 95% CI, -1.05 to -0.03). Fat mass (WMD, -0.98 kg; 95% CI, -2.32 to 0.36) tended to decrease in the IFD group with a significant increase in adiponectin (WMD, 1008.9 ng/mL; 95% CI, 140.5 to 1877.3) and a decrease in leptin (WMD, -0.51 ng/mL; 95% CI, -0.77 to -0.24) levels. An IFD may provide a significant metabolic benefit by improving glycemic control, insulin resistance, and adipokine concentration with a reduction of BMI in adults. KEYWORDS: body mass index; glucose metabolism; insulin resistance; intermittent fasting
  4. A brief diet intervention can reduce symptoms of depression in young adults - A randomised controlled trial. Francis HM, Stevenson RJ, Chambers JR, Gupta D, Newey B, Lim CK. PLoS One. 2019 Oct 9;14(10):e0222768. doi: 10.1371/journal.pone.0222768. eCollection 2019. PMID: 31596866 https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0222768&type=printable Abstract There is strong epidemiological evidence that poor diet is associated with depression. The reverse has also been shown, namely that eating a healthy diet rich in fruit, vegetables, fish and lean meat, is associated with reduced risk of depression. To date, only one randomised controlled trial (RCT) has been conducted with elevated depression symptoms being an inclusion criterion, with results showing that a diet intervention can reduce clinical levels of depression. No such RCTs have been performed in young adults. Young adults with elevated levels of depression symptoms and who habitually consume a poor diet were randomly allocated to a brief 3-week diet intervention (Diet Group) or a habitual diet control group (Control Group). The primary and secondary outcome measures assessed at baseline and after the intervention included symptoms of depression (Centre for Epidemiological Studies Depression Scale; CESD-R; and Depression Anxiety and Stress Scale- 21 depression subscale; DASS-21-D), current mood (Profile of Mood States), self-efficacy (New General Self-Efficacy Scale) and memory (Hopkins Verbal Learning Test). Diet compliance was measured via self-report questionnaires and spectrophotometry. One-hundred-and-one individuals were enrolled in the study and randomly assigned to the Diet Group or the Control Group. Upon completion of the study, there was complete data for 38 individuals in each group. There was good compliance with the diet intervention recommendations assessed using self-report and spectrophotometry. The Diet group had significantly lower self-reported depression symptoms than the Control Group on the CESD-R (p = 0.007, Cohen's d = 0.65) and DASS-21 depression subscale (p = 0.002, Cohen's d = 0.75) controlling for baseline scores on these scales. Reduced DASS-21 depression subscale scores were maintained on follow up phone call 3 months later (p = .009). These results are the first to show that young adults with elevated depression symptoms can engage in and adhere to a diet intervention, and that this can reduce symptoms of depression. The findings provide justification for future research into the duration of these benefits, the impacts of varying diet composition, and their biological basis.
  5. Association between Macronutrient Intake and Excessive Daytime Sleepiness: An Iso-Caloric Substitution Analysis from the North West Adelaide Health Study. Melaku YA, Reynolds AC, Gill TK, Appleton S, Adams R. Nutrients. 2019 Oct 5;11(10). pii: E2374. doi: 10.3390/nu11102374. PMID: 31590356 Abstract Epidemiological evidence on the association between macronutrient intake and excessive daytime sleepiness (EDS) is scarce. Using data from the North West Adelaide Health Study, we aimed to determine the association between iso-caloric substitution of macronutrients and EDS. Data from 1997 adults aged ≥ 24 years were analyzed. Daytime sleepiness was measured using the Epworth Sleepiness Scale, a score ≥ 11 was considered EDS. Dietary intake data were collected using a food frequency questionnaire. We determined absolute and relative energy intake based on consumption of saturated and unsaturated fats, protein, and carbohydrate. Odds ratios (ORs) were used to determine the associations using log-binomial logistic regression with and without iso-caloric substitution methods, and models were adjusted for confounders. The prevalence of EDS in the sample was 10.6%. After adjusting for potential confounders, substituting 5% energy intake from protein with an equal amount of saturated fat (OR = 1.57; 95% CI: 1.00-2.45) and carbohydrate (OR = 1.23; 95% CI: 0.92-1.65) increased the odds of EDS. When carbohydrate was substituted with saturated fat (OR = 1.27; 95% CI: 0.93-1.59), the odds of EDS were increased. The odds of EDS were lower when saturated fat was substituted with unsaturated fat (OR = 0.74; 95% CI: 0.51-1.06), protein (OR = 0.63; 95% CI: 0.41-0.99) or carbohydrate (OR = 0.79; 95% CI: 0.57-1.08). While these results were consistent over different iso-caloric substitution methods, inconsistent results were found with standard regression. While substitution of fat and carbohydrate with protein was inversely associated with EDS, substitution of protein with fat and carbohydrate was positively associated with EDS. Randomized trials are needed to confirm if dietary interventions can be used to improve daytime alertness in those with EDS. KEYWORDS: carbohydrate; excessive daytime sleepiness; fat; protein; saturated fat; sleepiness; substitution analysis; unsaturated fat Heart Histopathology and Mitochondrial Ultrastructure in Aged Rats Fed for 24 Months on Different Unsaturated Fats (Virgin Olive Oil, Sunflower Oil or Fish Oil) and Affected by Different Longevity. Navarro-Hortal MD, Ramírez-Tortosa CL, Varela-López A, Romero-Márquez JM, Ochoa JJ, Ramírez-Tortosa M, Forbes-Hernández TY, Granados-Principal S, Battino M, Quiles JL. Nutrients. 2019 Oct 7;11(10). pii: E2390. doi: 10.3390/nu11102390. PMID: 31591312 [pdf availed by title Google.] Abstract Diet plays a decisive role in heart physiology, with lipids having especial importance in pathology prevention and development. This study aimed to investigate how dietary lipids varying in lipid profile (virgin olive oil, sunflower oil or fish oil) affected the heart of rats during aging. Heart histopathology, mitochondrial morphometry, and oxidative status were assessed. Typical histopathological features associated with aging, such as valvular lesions, endomyocardical hyperplasia, or papillary muscle calcification, were found at a low extent in all the experimental groups. The most relevant finding was that inflammation registered by fish oil group was lower compared to the other treatments. At the ultrastructural level, heart mitochondrial area, perimeter, and aspect ratio were higher in fish oil-fed rats than in those fed on sunflower oil. Concerning oxidative stress markers, there were differences only in coenzyme Q levels and catalase activity, lower in sunflower oil-fed animals compared with those fed on fish oil. In summary, dietary intake for a long period on dietary fats with different fatty acids profile led to differences in some aspects associated with the aging process at the heart. Fish oil seems to be the fat most protective of heart during aging. KEYWORDS: MUFA; PUFA; aging; fibrosis; histology; inflammation; mitochondrial morphology; n-3; n-6 Total Fermented Dairy Food Intake Is Inversely Associated with Cardiovascular Disease Risk in Women. Buziau AM, Soedamah-Muthu SS, Geleijnse JM, Mishra GD. J Nutr. 2019 Oct 1;149(10):1797-1804. doi: 10.1093/jn/nxz128. PMID: 31192363 Abstract BACKGROUND: The relation between fermented dairy consumption and type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in an Australian population remains to be established. OBJECTIVES: The aim of this study was to investigate the association between fermented dairy consumption and T2DM and CVD risk. METHODS: The Australian Longitudinal Study on Women's Health included Australian women (aged 45-50 y) at baseline in 2001, who were followed up through 5 surveys until 2016. Dietary intake was assessed through the use of a validated 101-item FFQ at baseline. Main study outcomes were self-reported physician-diagnosed T2DM and CVD. Logistic regression models adjusted for sociodemographic and lifestyle factors were used to estimate the association between dairy intake and T2DM and CVD risk. RESULTS: Of 7633 women free of diabetes at baseline, 701 (9.2%) developed T2DM during a maximum 15-y follow-up period. Women in the highest tertile of yogurt intake had lower adjusted odds of T2DM than those in the lowest tertile (OR: 0.81; 95% CI: 0.67, 0.99; P = 0.041). This relation became nonsignificant after adjustment for dietary variables and total energy intake (OR: 0.88; 95% CI: 0.71, 1.08; P = 0.21). Of 7679 women free of CVD at baseline, 835 (10.9%) cases of CVD were reported during follow-up. High intake of yogurt and total fermented dairy was associated with lower CVD risk (OR: 0.84; 95% CI: 0.70, 1.00; P = 0.05, 0.80; 0.67, 0.96; 0.017, respectively) than observed in the lowest tertile of dairy product intake. Additional adjustment attenuated the relation (OR: 0.87; 95% CI: 0.72, 1.04; P = 0.13, 0.83; 0.69, 1.00; 0.048, for yogurt and total fermented dairy, respectively). No associations were found with other dairy groups. CONCLUSION: The findings from this population-based study of Australian women suggest an inverse association between total fermented dairy intake and CVD risk, which may partly be accounted for by other dietary components. KEYWORDS: Australia; cardiovascular disease; cheese; coronary heart disease; dairy; fermented dairy; stroke; type 2 diabetes mellitus; women's health; yogurt
  6. AlPater

    Al's CR updates

    Dietary restriction regimens for fighting kidney disease: Insights from rodent studies. Singh G, Krishan P. Exp Gerontol. 2019 Oct 5:110738. doi: 10.1016/j.exger.2019.110738. [Epub ahead of print] Review. PMID: 31593758 Abstract This review critically discusses the research findings on the effects of various dietary restriction regimens in rodent models of kidney disease. Long-term caloric restriction executed at both early and progressive stages of kidney disease was found to exert beneficial effects in rodents. Moreover, some studies have also demonstrated the efficacy of short-term caloric restriction in treating the kidney disease of variable aetiologies possibly by improving mitochondrial dysfunction, autophagy process and suppression of inflammation. However, the mechanisms underlying these short-term caloric restriction mediated protective effects in rodent models of kidney disease are not completely understood. Importantly, few available evidences have also suggested that carbohydrate restriction can exert beneficial effects in aging and experimentally induced renal injury models, but the mechanisms are not explored yet. Interestingly, the benefits of low protein diet in kidney disease models are extensively reported in literature. However, in most of these studies implementation of the low protein dietary regimen was found to associated with increased high carbohydrate and caloric intake (non-isocaloric). Thus, testing the effects of low protein diet under isocaloric conditions might further help to particularly understand the role of dietary protein content in pathology of kidney disease. Moreover, the direct evidences comparing the efficacy of various dietary restriction regimens in rodent models of kidney diseases are also scarce at present. KEYWORDS: Aging kidney disease; Autophagy; Carbohydrate restriction; Chronic renal failure; Diabetic nephropathy; Diet restriction; Low protein diet; Polycystic kidney disease
  7. The effects of omega-3 fatty acids on neuropsychological functioning and brain morphology in mid-life adults: a randomized clinical trial. Leckie RL, Lehman DE, Gianaros PJ, Erickson KI, Sereika SM, Kuan DCH, Manuck SB, Ryan CM, Yao JK, Muldoon MF. Psychol Med. 2019 Oct 4:1-10. doi: 10.1017/S0033291719002617. [Epub ahead of print] PMID: 31581959 Abstract BACKGROUND: The diet of most adults is low in fish and, therefore, provides limited quantities of the long-chain, omega-3 fatty acids (LCn-3FAs), eicosapentaenoic and docosahexaenoic acids (EPA, DHA). Since these compounds serve important roles in the brain, we sought to determine if healthy adults with low-LCn-3FA consumption would exhibit improvements in neuropsychological performance and parallel changes in brain morphology following repletion through fish oil supplementation. METHODS: In a randomized, controlled trial, 271 mid-life adults (30-54 years of age, 118 men, 153 women) consuming ⩽300 mg/day of LCn-3FAs received 18 weeks of supplementation with fish oil capsules (1400 mg/day of EPA and DHA) or matching placebo. All participants completed a neuropsychological test battery examining four cognitive domains: psychomotor speed, executive function, learning/episodic memory, and fluid intelligence. A subset of 122 underwent neuroimaging before and after supplementation to measure whole-brain and subcortical tissue volumes. RESULTS: Capsule adherence was over 95%, participant blinding was verified, and red blood cell EPA and DHA levels increased as expected. Supplementation did not affect performance in any of the four cognitive domains. Exploratory analyses revealed that, compared to placebo, fish oil supplementation improved executive function in participants with low-baseline DHA levels. No changes were observed in any indicator of brain morphology. CONCLUSIONS: In healthy mid-life adults reporting low-dietary intake, supplementation with LCn-3FAs in moderate dose for moderate duration did not affect neuropsychological performance or brain morphology. Whether salutary effects occur in individuals with particularly low-DHA exposure requires further study. KEYWORDS: Cognitive functioning; magnetic resonance imaging; neuropsychological performance; omega-3 fatty acids; randomized clinical trial Changes in Consumption of Sugary Beverages and Artificially Sweetened Beverages and Subsequent Risk of Type 2 Diabetes: Results From Three Large Prospective U.S. Cohorts of Women and Men. Drouin-Chartier JP, Zheng Y, Li Y, Malik V, Pan A, Bhupathiraju SN, Tobias DK, Manson JE, Willett WC, Hu FB. Diabetes Care. 2019 Oct 3. pii: dc190734. doi: 10.2337/dc19-0734. [Epub ahead of print] PMID: 31582428 Abstract OBJECTIVE: We evaluated the associations of long-term changes in consumption of sugary beverages (including sugar-sweetened beverages and 100% fruit juices) and artificially sweetened beverages (ASBs) with subsequent risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: We followed up 76,531 women in the Nurses' Health Study (1986-2012), 81,597 women in the Nurses' Health Study II (1991-2013), and 34,224 men in the Health Professionals' Follow-up Study (1986-2012). Changes in beverage consumption (in 8-ounce serving/day) were calculated from food frequency questionnaires administered every 4 years. Multivariable Cox proportional regression models were used to calculate hazard ratios for diabetes associated with changes in beverage consumption. Results of the three cohorts were pooled using an inverse variance-weighted, fixed-effect meta-analysis. RESULTS: During 2,783,210 person-years of follow-up, we documented 11,906 incident cases of type 2 diabetes. After adjustment for BMI and initial and changes in diet and lifestyle covariates, increasing total sugary beverage intake (including both sugar-sweetened beverages and 100% fruit juices) by >0.50 serving/day over a 4-year period was associated with a 16% (95% CI 1%, 34%) higher diabetes risk in the subsequent 4 years. Increasing ASB consumption by >0.50 serving/day was associated with 18% (2-36%) higher diabetes risk. Replacing one daily serving of sugary beverage with water, coffee or tea, but not ASB, was associated with a 2-10% lower diabetes risk. CONCLUSIONS: Increasing consumption of sugary beverages or ASBs was associated with a higher risk of type 2 diabetes, albeit the latter may be affected by reverse causation and surveillance bias. Effects of Conjugated Linoleic Acid Intake in the Form of Dietary Supplement or Enriched Food on C-Reactive Protein and Lipoprotein (a) Levels in Humans: A Literature Review and Meta-Analysis. Derakhshandeh-Rishehri SM, Rahbar AR, Ostovar A. Iran J Med Sci. 2019 Sep;44(5):359-373. doi: 10.30476/IJMS.2019.44949. Review. PMID: 31582860 Abstract BACKGROUND: C-reactive protein (CRP) and lipoprotein (a) (Lp[a]) play essential roles in cardiovascular disease incidence. This study aimed to review the association between the intake of conjugated linoleic acid (CLA) in the form of dietary supplement or enriched food with different treatment durations and the levels of Lp(a) and CRP in human studies. METHODS: All the articles published in Cochrane Library, ProQuest, Scopus, and Google Scholar from November 2014 to October 2015 were searched and the clinical trials on the effects of CLA on Lp(a) and CRP levels were assessed. Of the 2249 articles initially retrieved, 21 eligible randomized clinical trials were enrolled in this systematic review. The publication dates of the eligible articles ranged from 2005 to 2013. The mean difference and the standard deviation of changes in CRP and Lp(a) levels in intervention and control groups were used as effect-size measures for meta-analysis. The obtained data from the eligible randomized controlled trials were meta-analyzed using Stata, version 13. RESULTS: The intake of CLA as a dietary supplement led to a significant increase in CRP levels (standardized mean difference [SMD]=0.41, 95% CI: 0.28 to 0.54; P=0.001). Subgroup analysis based on the duration of CLA consumption showed that CLA consumption more than 24 weeks resulted in a significant increase in the levels of CRP (SMD=0.52, 95% CI: 0.36 to 0.68; P=0.001) and Lp(a) (SMD=0.24, 95% CI: 0.01 to 0.47; P=0.04). CONCLUSION: The current systematic review and meta-analysis showed that the long-term consumption of CLA increases the levels of CRP and Lp(a). KEYWORDS: C-reactive protein ; Lipoprotein (a) ; Meta-analysis; Conjugated linoleic acid
  8. The Efficacy And Safety Of Aspirin As The Primary Prevention Of Cardiovascular Disease: An Updated Meta-Analysis. Xie W, Luo Y, Liang X, Lin Z, Wang Z, Liu M. Ther Clin Risk Manag. 2019 Sep 24;15:1129-1140. doi: 10.2147/TCRM.S198403. eCollection 2019. PMID: 31576136 [pdf availed from PubMed abstact site.] Abstract PURPOSE: Information regarding the use of aspirin for patients with no known cardiovascular disease remains conflicting. We performed an updated meta-analysis to evaluate the efficacy and safety of aspirin for primary prevention of cardiovascular disease. PATIENTS AND METHODS: PubMed, MEDLINE, and Cochrane library databases were searched for randomized controlled trials comparing aspirin with placebos or no treatment published up until November 1, 2018. The primary efficacy endpoint was all-cause death. The secondary endpoints included cardiovascular death, myocardial infarction, and stroke. The safety endpoints included major bleeding, gastrointestinal bleeding, and hemorrhagic stroke. RESULTS: Fourteen studies were included. Aspirin use was associated with a lower risk of myocardial infarction than placebo use or no treatment (risk ratio [RR], 0.83, 95% confidence interval [CI]: 0.73-0.95, P = 0.005). Additionally, compared with the control groups, aspirin use was not associated with a lower risk of all-cause mortality or cardiovascular mortality. In terms of safety, aspirin use was associated with a higher risk of major bleeding (RR, 1.40, 95% CI: 1.25-1.57, P = 0.000), gastrointestinal bleeding (RR, 1.58, 95% CI: 1.25-1.99, P = 0.000), and hemorrhagic stroke (RR, 1.30, 95% CI: 1.06-1.60, P = 0.011). Furthermore, the treatment effect was not significantly modified by patients' clinical characteristics. No publication bias was present. CONCLUSION: Aspirin use reduced the myocardial infarction risk in patients without known cardiovascular disease, but had no effect in terms of reducing the risk of all-cause death, cardiovascular death, and stroke, and increased the risk of major bleeding, gastrointestinal bleeding, and hemorrhagic stroke. KEYWORDS: aspirin; cardiovascular disease; meta-analysis; primary prevention Cause-specific mortality in the general population with transient dipstick-proteinuria. Nagai K, Yamagata K, Iseki K, Moriyama T, Tsuruya K, Fujimoto S, Narita I, Konta T, Kondo M, Kasahara M, Shibagaki Y, Asahi K, Watanabe T. PLoS One. 2019 Oct 2;14(10):e0223005. doi: 10.1371/journal.pone.0223005. eCollection 2019. PMID: 31577820 Abstract Recently, changes in urinary albumin and in GFR have been recognized as risk factors for the development of end-stage kidney disease and mortality. Though most clinical epidemiology studies of chronic kidney disease (CKD) used renal function and proteinuria at baseline alone, definitive diagnosis of CKD with multiple measurements intensifies the differences in the risk for mortality between the CKD and non-CKD populations. We hypothesized that a transient diagnosis of proteinuria and reduced renal function each indicate a significantly higher mortality compared to definitive non-CKD as the negative control and lower mortality compared with definitive CKD as the positive control. The present longitudinal study evaluated a general-population cohort of 338,094 persons who received annual health checkups, with a median 4.3-year study period. There were 2,481 deaths, including 510 CVD deaths (20.6%) and 1,328 cancer deaths (53.5%), and mortality risk was evaluated for transient proteinuria and for transiently reduced renal function. The hazard ratios (HRs) for all-cause mortality and cancer mortality were not significant, but that for cardiovascular mortality was significantly higher for transient proteinuria (HR, 1.94 [95% confidence interval, 1.27-2.96] in men and 2.78 [1.50-5.16] in women). On the other hand, transiently reduced renal function was not significant for either cardiovascular mortality risk or cancer mortality risk. We surmise that this is the first study of the mortality risk of transient dipstick proteinuria in a large general-population cohort with cause-specific death registration. Transiently positive proteinuria appears to be a significant risk specifically for cardiovascular mortality compared with definitely negative for proteinuria. A prospective analysis of red and processed meat consumption and risk of colorectal cancer in women. Mehta SS, Arroyave WD, Lunn RM, Park YM, Boyd WA, Sandler DP. Cancer Epidemiol Biomarkers Prev. 2019 Oct 1. pii: cebp.0459.2019. doi: 10.1158/1055-9965.EPI-19-0459. [Epub ahead of print] PMID: 31575555 Abstract BACKGROUND: Red and processed meats have been implicated as risk factors in the development of colorectal cancer (CRC) in U.S. women, but associations with cooking practices are less well established. METHODS: Data are from the Sister Study, a cohort of women 35-74 years old from U.S. and Puerto Rico who have a sister diagnosed with breast cancer. Red and processed meat consumption, meat cooking practices, and intake of common meat products were collected at baseline using self-administered questionnaires (N=48,704). Multivariable hazard ratios (HRadj) and 95% confidence intervals (95%CIs) were estimated. RESULTS: During a median 8.7 years follow-up (range <1-12.7 years), 216 CRC cases were diagnosed. In categorical analyses, an increased risk of CRC was seen in the highest quartile of processed meat consumption compared to the lowest [HRadj=1.52 (95%CI: 1.01-2.30); p-trend: 0.02], and for specific meat products, including breakfast sausages (HRadj=1.85 [95%CI: 1.30-2.64]) and bacon (HRadj=1.46 [95%CI: 1.01-2.11]). The adjusted HR for the highest quartile of red meat consumption was 1.04 (95%CI: 0.68-1.60), and little evidence of association was observed for cooking practices or doneness of red meat. We observed positive associations with specific red meat products when cooking methods were considered; e.g., grilled/ barbequed steaks (HRadj=2.23 [95%CI: 1.20-4.14]) and hamburgers (HRadj=1.98 [95%CI: 1.00-3.91]). CONCLUSIONS: Higher reported daily intake of processed meats and consumption of barbecued/grilled red meat products were associated with increased risk of CRC in women. IMPACT: Variability in CRC risk by meat type and cooking method should be considered when evaluating meat consumption. Prospective randomized controlled pilot study on the effects of almond consumption on skin lipids and wrinkles. Foolad N, Vaughn AR, Rybak I, Burney WA, Chodur GM, Newman JW, Steinberg FM, Sivamani RK. Phytother Res. 2019 Oct 1. doi: 10.1002/ptr.6495. [Epub ahead of print] PMID: 31576607 https://onlinelibrary.wiley.com/doi/epdf/10.1002/ptr.6495 Abstract OBJECTIVE: Almonds are a rich source of fatty acids and antioxidants, and their supplementation is known to significantly modulate serum lipids. The effects of almond on the skin's lipid barrier and the appearance of wrinkles have not yet been elucidated. The aim of this study was to investigate the effects of almond consumption on facial sebum production and wrinkles. METHODS: This was a prospective, investigator-blinded, randomized controlled trial in which subjects consumed 20% of their daily energy consumption in either almonds or a calorie-matched snack for 16 weeks. This study was completed at the UC Davis Dermatology clinic. Participants were a volunteer sample of generally healthy postmenopausal females with Fitzpatrick skin types 1 and 2. A facial photograph and image analysis system was used to obtain standardized photographs and information on wrinkle width and severity at 0, 8, and 16 weeks. Measurements of transepidermal water loss and sebum production were also completed at 0, 8, and 16 weeks. RESULTS: Fifty healthy postmenopausal females were recruited, 31 participants were enrolled, and 28 completed the study. Under photographic analysis, the almond group had significantly decreased wrinkle severity and width compared with the control group at 16 weeks (p < .02). Changes in skin barrier function were nonsignificant, measured by the transepidermal water loss (p = .65) between the almond and control groups relative to baseline after 16 weeks. No adverse effects were reported. CONCLUSION: Our study demonstrates that daily almond consumption may reduce wrinkle severity in postmenopausal females to potentially have natural antiaging benefits. KEYWORDS: almonds; fatty acids; lipids; skin barrier; skin physiology/structure; wrinkles
  9. AlPater

    Al's CR updates

    Calorie-Restriction-Induced Insulin Sensitivity Is Mediated by Adipose mTORC2 and Not Required for Lifespan Extension. Yu D, Tomasiewicz JL, Yang SE, Miller BR, Wakai MH, Sherman DS, Cummings NE, Baar EL, Brinkman JA, Syed FA, Lamming DW. Cell Rep. 2019 Oct 1;29(1):236-248.e3. doi: 10.1016/j.celrep.2019.08.084. PMID: 31577953 https://www.cell.com/cell-reports/pdf/S2211-1247(19)31146-5.pdf Abstract Calorie restriction (CR) extends the healthspan and lifespan of diverse species. In mammals, a broadly conserved metabolic effect of CR is improved insulin sensitivity, which may mediate the beneficial effects of a CR diet. This model has been challenged by the identification of interventions that extend lifespan and healthspan yet promote insulin resistance. These include rapamycin, which extends mouse lifespan yet induces insulin resistance by disrupting mTORC2 (mechanistic target of rapamycin complex 2). Here, we induce insulin resistance by genetically disrupting adipose mTORC2 via tissue-specific deletion of the mTORC2 component Rictor (AQ-RKO). Loss of adipose mTORC2 blunts the metabolic adaptation to CR and prevents whole-body sensitization to insulin. Despite this, AQ-RKO mice subject to CR experience the same increase in fitness and lifespan on a CR diet as wild-type mice. We conclude that the CR-induced improvement in insulin sensitivity is dispensable for the effects of CR on fitness and longevity. KEYWORDS: Rictor; adipose; calorie restriction; fitness; frailty; healthspan; insulin sensitivity; lifespan; lipogenesis; mTORC2
  10. Dietary zinc intake, supplemental zinc intake and serum zinc levels and the prevalence of kidney stones in adults. Sun Y, Wang Y, Wang D, Zhou Q. J Trace Elem Med Biol. 2019 Sep 24:126410. doi: 10.1016/j.jtemb.2019.126410. [Epub ahead of print] PMID: 31570252 Abstract OBJECTIVE: The association between zinc intake and the risk of kidney stones remains controversial. We examined the associations between dietary zinc intake, supplemental zinc intake and serum zinc levels and the prevalence of kidney stones in adults. METHODS: Adult participants from the 2007-2016 NHANES were included. Restricted cubic splines were adopted to assess the dose-response relationships. RESULTS: Dietary zinc intake was linearly associated with the prevalence of kidney stones (Pfor non-linearity = 0.50), and the odds ratios (95% confidence intervals) of kidney stones were 0.75 (0.51-1.04) for 10 mg/day, 0.65 (0.39-0.97) for 20 mg/day, 0.53 (0.30-0.94) for 30 mg/day and 0.45 (0.22-0.95) for 40 mg/day. The linear relationship was also observed among women and overweight/obese individuals. No association was found between supplemental zinc intake and the prevalence of kidney stones. A non-linear relationship was found between serum zinc levels and the prevalence of kidney stones (Pfor non-linearity = 0.02), and the odds ratios (95% confidence intervals) of kidney stones were 0.52 (0.33-0.82) for 70 ug/dL, 0.43 (0.24-0.77) for 90 ug/dL, 0.56 (0.32-0.98) for 110 ug/dL and 0.77 (0.37-1.62) for 130 ug/dL. The non-linear relationship was also observed among men and overweight/obese individuals. CONCLUSIONS: Dietary zinc intake and serum zinc levels were inversely associated with the prevalence of kidney stones in adults, and there may be effect modification by participant sex and body mass index. The present analysis is limited in its ability to establish causality. KEYWORDS: Adults; Dietary zinc intake; Kidney stones; National Health and Nutrition Examination Survey; Serum zinc levels; Supplemental zinc intake How risky is eating red meat? New studies provoke controversy The studies do not say red meat and processed meats like hot dogs and bacon are healthy The Associated Press · Posted: Oct 01, 2019 https://www.cbc.ca/news/canada/hamilton/how-risky-is-eating-red-meat-new-studies-provoke-controversy-1.5303941 >>>>>>>>>>>>>>>>>>>>>>>> Effect of Lower Versus Higher Red Meat Intake on Cardiometabolic and Cancer Outcomes: A Systematic Review of Randomized Trials. Zeraatkar D, Johnston BC, Bartoszko J, Cheung K, Bala MM, Valli C, Rabassa M, Sit D, Milio K, Sadeghirad B, Agarwal A, Zea AM, Lee Y, Han MA, Vernooij RWM, Alonso-Coello P, Guyatt GH, El Dib R. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-0622. [Epub ahead of print] PMID: 31569236 https://annals.org/aim/fullarticle/2752326/effect-lower-versus-higher-red-meat-intake-cardiometabolic-cancer-outcomes Abstract BACKGROUND: Few randomized trials have evaluated the effect of reducing red meat intake on clinically important outcomes. PURPOSE: To summarize the effect of lower versus higher red meat intake on the incidence of cardiometabolic and cancer outcomes in adults. DATA SOURCES: EMBASE, CENTRAL, CINAHL, Web of Science, and ProQuest from inception to July 2018 and MEDLINE from inception to April 2019, without language restrictions. STUDY SELECTION: Randomized trials (published in any language) comparing diets lower in red meat with diets higher in red meat that differed by a gradient of at least 1 serving per week for 6 months or more. DATA EXTRACTION: Teams of 2 reviewers independently extracted data and assessed the risk of bias and the certainty of the evidence. DATA SYNTHESIS: Of 12 eligible trials, a single trial enrolling 48 835 women provided the most credible, though still low-certainty, evidence that diets lower in red meat may have little or no effect on all-cause mortality (hazard ratio , 0.99 [95% CI, 0.95 to 1.03], cardiovascular mortality (HR, 0.98 [CI, 0.91 to 1.06]), and cardiovascular disease (HR, 0.99 [CI, 0.94 to 1.05]). That trial also provided low- to very-low-certainty evidence that diets lower in red meat may have little or no effect on total cancer mortality (HR, 0.95 [CI, 0.89 to 1.01]) and the incidence of cancer, including colorectal cancer (HR, 1.04 [CI, 0.90 to 1.20]) and breast cancer (HR, 0.97 [0.90 to 1.04]). LIMITATIONS: There were few trials, most addressing only surrogate outcomes, with heterogeneous comparators and small gradients in red meat consumption between lower versus higher intake groups. CONCLUSION: Low- to very-low-certainty evidence suggests that diets restricted in red meat may have little or no effect on major cardiometabolic outcomes and cancer mortality and incidence. >>>>>>>>>>>>> Patterns of Red and Processed Meat Consumption and Risk for Cardiometabolic and Cancer Outcomes: A Systematic Review and Meta-analysis of Cohort Studies. Vernooij RWM, Zeraatkar D, Han MA, El Dib R, Zworth M, Milio K, Sit D, Lee Y, Gomaa H, Valli C, Swierz MJ, Chang Y, Hanna SE, Brauer PM, Sievenpiper J, de Souza R, Alonso-Coello P, Bala MM, Guyatt GH, Johnston BC. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1583. [Epub ahead of print] PMID: 31569217 https://annals.org/aim/fullarticle/2752327/patterns-red-processed-meat-consumption-risk-cardiometabolic-cancer-outcomes-systematic Abstract BACKGROUND: Studying dietary patterns may provide insights into the potential effects of red and processed meat on health outcomes. PURPOSE: To evaluate the effect of dietary patterns, including different amounts of red or processed meat, on all-cause mortality, cardiometabolic outcomes, and cancer incidence and mortality. DATA SOURCES: Systematic search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and ProQuest Dissertations & Theses Global from inception to April 2019 with no restrictions on year or language. STUDY SELECTION: Teams of 2 reviewers independently screened search results and included prospective cohort studies with 1000 or more participants that reported on the association between dietary patterns and health outcomes. DATA EXTRACTION: Two reviewers independently extracted data, assessed risk of bias, and evaluated the certainty of evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. DATA SYNTHESIS: Eligible studies that followed patients for 2 to 34 years revealed low- to very-low-certainty evidence that dietary patterns lower in red and processed meat intake result in very small or possibly small decreases in all-cause mortality, cancer mortality and incidence, cardiovascular mortality, nonfatal coronary heart disease, fatal and nonfatal myocardial infarction, and type 2 diabetes. For all-cause, cancer, and cardiovascular mortality and incidence of some types of cancer, the total sample included more than 400 000 patients; for other outcomes, total samples included 4000 to more than 300 000 patients. LIMITATION: Observational studies are prone to residual confounding, and these studies provide low- or very-low-certainty evidence according to the GRADE criteria. CONCLUSION: Low- or very-low-certainty evidence suggests that dietary patterns with less red and processed meat intake may result in very small reductions in adverse cardiometabolic and cancer outcomes. >>>>>>>>>>>>>>>>> Reduction of Red and Processed Meat Intake and Cancer Mortality and Incidence: A Systematic Review and Meta-analysis of Cohort Studies. Han MA, Zeraatkar D, Guyatt GH, Vernooij RWM, El Dib R, Zhang Y, Algarni A, Leung G, Storman D, Valli C, Rabassa M, Rehman N, Parvizian MK, Zworth M, Bartoszko JJ, Lopes LC, Sit D, Bala MM, Alonso-Coello P, Johnston BC. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-0699. [Epub ahead of print] PMID: 31569214 https://annals.org/aim/fullarticle/2752321/reduction-red-processed-meat-intake-cancer-mortality-incidence-systematic-review Abstract BACKGROUND: Cancer incidence has continuously increased over the past few centuries and represents a major health burden worldwide. PURPOSE: To evaluate the possible causal relationship between intake of red and processed meat and cancer mortality and incidence. DATA SOURCES: Embase, Cochrane Central Register of Controlled Trials, Web of Science, CINAHL, and ProQuest from inception until July 2018 and MEDLINE from inception until April 2019 without language restrictions. STUDY SELECTION: Cohort studies that included more than 1000 adults and reported the association between consumption of unprocessed red and processed meat and cancer mortality and incidence. DATA EXTRACTION: Teams of 2 reviewers independently extracted data and assessed risk of bias; 1 reviewer evaluated the certainty of evidence, which was confirmed or revised by the senior reviewer. DATA SYNTHESIS: Of 118 articles (56 cohorts) with more than 6 million participants, 73 articles were eligible for the dose-response meta-analyses, 30 addressed cancer mortality, and 80 reported cancer incidence. Low-certainty evidence suggested that an intake reduction of 3 servings of unprocessed meat per week was associated with a very small reduction in overall cancer mortality over a lifetime. Evidence of low to very low certainty suggested that each intake reduction of 3 servings of processed meat per week was associated with very small decreases in overall cancer mortality over a lifetime; prostate cancer mortality; and incidence of esophageal, colorectal, and breast cancer. LIMITATION: Limited causal inferences due to residual confounding in observational studies, risk of bias due to limitations in diet assessment and adjustment for confounders, recall bias in dietary assessment, and insufficient data for planned subgroup analyses. CONCLUSION: The possible absolute effects of red and processed meat consumption on cancer mortality and incidence are very small, and the certainty of evidence is low to very low. >>>>>>>>>>>>>>>>>>>>>>>> Red and Processed Meat Consumption and Risk for All-Cause Mortality and Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Cohort Studies. Zeraatkar D, Han MA, Guyatt GH, Vernooij RWM, El Dib R, Cheung K, Milio K, Zworth M, Bartoszko JJ, Valli C, Rabassa M, Lee Y, Zajac J, Prokop-Dorner A, Lo C, Bala MM, Alonso-Coello P, Hanna SE, Johnston BC. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-0655. [Epub ahead of print] PMID: 31569213 https://annals.org/aim/fullarticle/2752320/red-processed-meat-consumption-risk-all-cause-mortality-cardiometabolic-outcomes Abstract BACKGROUND: Dietary guidelines generally recommend limiting intake of red and processed meat. However, the quality of evidence implicating red and processed meat in adverse health outcomes remains unclear. PURPOSE: To evaluate the association between red and processed meat consumption and all-cause mortality, cardiometabolic outcomes, quality of life, and satisfaction with diet among adults. DATA SOURCES: EMBASE (Elsevier), Cochrane Central Register of Controlled Trials (Wiley), Web of Science (Clarivate Analytics), CINAHL (EBSCO), and ProQuest from inception until July 2018 and MEDLINE from inception until April 2019, without language restrictions, as well as bibliographies of relevant articles. STUDY SELECTION: Cohort studies with at least 1000 participants that reported an association between unprocessed red or processed meat intake and outcomes of interest. DATA EXTRACTION: Teams of 2 reviewers independently extracted data and assessed risk of bias. One investigator assessed certainty of evidence, and the senior investigator confirmed the assessments. DATA SYNTHESIS: Of 61 articles reporting on 55 cohorts with more than 4 million participants, none addressed quality of life or satisfaction with diet. Low-certainty evidence was found that a reduction in unprocessed red meat intake of 3 servings per week is associated with a very small reduction in risk for cardiovascular mortality, stroke, myocardial infarction (MI), and type 2 diabetes. Likewise, low-certainty evidence was found that a reduction in processed meat intake of 3 servings per week is associated with a very small decrease in risk for all-cause mortality, cardiovascular mortality, stroke, MI, and type 2 diabetes. LIMITATION: Inadequate adjustment for known confounders, residual confounding due to observational design, and recall bias associated with dietary measurement. CONCLUSION: The magnitude of association between red and processed meat consumption and all-cause mortality and adverse cardiometabolic outcomes is very small, and the evidence is of low certainty. >>>>>>>>>>>>>>>>>>>>>>>>>>> Dietary components and risk of cardiovascular disease and all-cause mortality: a review of evidence from meta-analyses. Kwok CS, Gulati M, Michos ED, Potts J, Wu P, Watson L, Loke YK, Mallen C, Mamas MA. Eur J Prev Cardiol. 2019 Sep;26(13):1415-1429. doi: 10.1177/2047487319843667. Epub 2019 Apr 11. PMID: 30971126 Abstract AIMS: The optimal diet for cardiovascular health is controversial. The aim of this review is to summarize the highest level of evidence and rank the risk associated with each individual component of diet within its food group. METHODS AND RESULTS: A systematic search of PudMed was performed to identify the highest level of evidence available from systematic reviews or meta-analyses that evaluated different dietary components and their associated risk of all-cause mortality and cardiovascular disease. A total of 16 reviews were included for dietary food item and all-cause mortality and 17 reviews for cardiovascular disease. Carbohydrates were associated with a reduced risk of all-cause mortality (whole grain bread: relative risk (RR) 0.85, 95% confidence interval (CI) 0.82-0.89; breakfast cereal: RR 0.88, 95% CI 0.83-0.92; oats/oatmeal: RR 0.88, 95% CI 0.83-0.92). Fish consumption was associated with a small benefit (RR 0.98, 95% CI 0.97-1.00) and processed meat appeared to be harmful (RR 1.25, 95% CI 1.07-1.45). Root vegetables (RR 0.76, 95% CI 0.66-0.88), green leafy vegetables/salad (RR 0.78, 95% CI 0.71-0.86), cooked vegetables (RR 0.89, 95% CI 0.80-0.99) and cruciferous vegetables (RR 0.90, 95% CI 0.85-0.95) were associated with reductions in all-cause mortality. Increased mortality was associated with the consumption of tinned fruit (RR 1.14, 95% CI 1.07-1.21). Nuts were associated with a reduced risk of mortality in a dose-response relationship (all nuts: RR 0.78, 95% CI 0.72-0.84; tree nuts: RR 0.82, 95% CI 0.75-0.90; and peanuts: RR 0.77, 95% CI 0.69-0.86). For cardiovascular disease, similar associations for benefit were observed for carbohydrates, nuts and fish, but red meat and processed meat were associated with harm. CONCLUSIONS: Many dietary components appear to be beneficial for cardiovascular disease and mortality, including grains, fish, nuts and vegetables, but processed meat and tinned fruit appear to be harmful. KEYWORDS: Diet; epidemiology; systematic review
  11. Efficacy of l-carnitine supplementation for management of blood lipids: A systematic review and dose-response meta-analysis of randomized controlled trials. Askarpour M, Hadi A, Symonds ME, Miraghajani M, Omid Sadeghi, Sheikhi A, Ghaedi E. Nutr Metab Cardiovasc Dis. 2019 Jul 24. pii: S0939-4753(19)30280-7. doi: 10.1016/j.numecd.2019.07.012. [Epub ahead of print] PMID: 31561944 Abstract BACKGROUND AND AIM: l-carnitine has an important role in fatty acid metabolism and could therefore act as an adjuvant agent in the improvement of dyslipidemia. The purpose of present systematic review and meta-analysis was to critically assess the efficacy of l-carnitine supplementation on lipid profiles. METHODS AND RESULTS: We performed a systematic search of all available randomized controlled trials (RCTs) in the following databases: Scopus, PubMed, ISI Web of Science, The Cochrane Library. Mean difference (MD) of any effect was calculated using a random-effects model. In total, there were 55 eligible RCTs included with 58 arms, and meta-analysis revealed that l-carnitine supplementation significantly reduced total cholesterol (TC) (56 arms-MD: -8.53 mg/dl, 95% CI: -13.46, -3.6, I2: 93%), low-density lipoprotein-cholesterol (LDL-C) (47 arms-MD: -5.48 mg/dl, 95% CI: -8.49, -2.47, I2: 94.5) and triglyceride (TG) (56 arms-MD: -9.44 mg/dl, 95% CI: -16.02, -2.87, I2: 91.8). It also increased high density lipoprotein-cholesterol (HDL-C) (51 arms-MD:1.64 mg/dl, 95% CI:0.54, 2.75, I2: 92.2). l-carnitine supplementation reduced TC in non-linear fashion based on dosage (r = 21.11). Meta-regression analysis indicated a linear relationship between dose of l-carnitine and absolute change in TC (p = 0.029) and LDL-C (p = 0.013). Subgroup analyses showed that l-carnitine supplementation did not change TC, LDL-C and TG in patients under hemodialysis treatment. Intravenous l-carnitine and lower doses (>2 g/day) had no effect on TC, LDL-C and triglycerides. CONCLUSION: l-carnitine supplementation at doses above 2 g/d has favorable effects on patients' lipid profiles, but is modulated on participant health and route of administration. KEYWORDS: Lipid profile; Meta-analysis; Systematic review; l-carnitine Alcohol Consumption and Risk of Dementia and Cognitive Decline Among Older Adults With or Without Mild Cognitive Impairment. Koch M, Fitzpatrick AL, Rapp SR, Nahin RL, Williamson JD, Lopez OL, DeKosky ST, Kuller LH, Mackey RH, Mukamal KJ, Jensen MK, Sink KM. JAMA Netw Open. 2019 Sep 4;2(9):e1910319. doi: 10.1001/jamanetworkopen.2019.10319. PMID: 31560382 Abstract IMPORTANCE: Substantial heterogeneity and uncertainty exist in the observed associations between alcohol consumption and dementia. OBJECTIVE: To assess the association between alcohol consumption and dementia and the roles of mild cognitive impairment (MCI) and apolipoprotein E ε4 (APOE E4) genotype in modifying this association. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the Ginkgo Evaluation of Memory Study, conducted from 2000 to 2008 among US community-dwelling participants. This study analyzed 3021 participants aged 72 years and older who were free of dementia. Data analysis was performed from 2017 to 2018. EXPOSURES: Self-reported alcohol consumption, drinking frequency, and quantity. MAIN OUTCOMES AND MEASURES: Using multivariable proportional hazards regression and linear mixed models, the risk of dementia and the rate of change over time in the Modified Mini-Mental State Examination were estimated. RESULTS: Among 3021 participants, the median (interquartile range) age was 78 (76-80) years; 1395 (46.2%) were female. During a median (interquartile range) follow-up of 6.0 (4.9-6.5) years, 512 cases of dementia occurred. For 7.1 to 14.0 drinks per week compared with less than 1.0 drink per week, the hazard ratios for dementia were 0.63 (95% CI, 0.38-1.06) among 2548 participants without MCI and 0.93 (95% CI, 0.47-1.84) among 473 participants with MCI. Among participants with MCI, the hazard ratio for dementia was 1.72 (95% CI, 0.87-3.40) for more than 14.0 drinks per week compared with less than 1.0 drink per week. The association of alcohol intake with dementia differed for participants with and without baseline MCI (P for interaction = .03). Among participants without MCI, daily low-quantity drinking was associated with lower dementia risk than infrequent higher-quantity drinking (hazard ratio, 0.45; 95% CI, 0.23-0.89; P = .02). Findings were consistent when stratified by sex, age, and APOE E4 genotype. Compared with drinking less than 1.0 drink per week, complete abstention (in participants without MCI) and the consumption of more than 14.0 drinks per week (in participants with MCI) were associated with lower Modified Mini-Mental State Examination scores (mean difference at follow-up compared with baseline, -0.46 point [95% CI, -0.87 to -0.04 point] and -3.51 points [95% CI, -5.75 to -1.27 points], respectively). CONCLUSIONS AND RELEVANCE: In this study, complete abstention and consuming more than 14.0 drinks per week (compared with drinking <1.0 drink per week) were associated with lower cognitive scores among participants aged 72 years and older. Particular caution is needed among individuals with MCI who continue to drink alcohol. Why It Was Easier to Be Skinny in the 1980s A study finds that people today who eat and exercise the same amount as people 20 years ago are still fatter. The Atlantic Olga Khazan >>>>>>>>>>>>>>>>>>>>>>> Secular differences in the association between caloric intake, macronutrient intake, and physical activity with obesity. Brown RE, Sharma AM, Ardern CI, Mirdamadi P, Mirdamadi P, Kuk JL. Obes Res Clin Pract. 2016 May-Jun;10(3):243-55. doi: 10.1016/j.orcp.2015.08.007. Epub 2015 Sep 14. PMID: 26383959 Abstract BACKGROUND: To determine whether the relationship between caloric intake, macronutrient intake, and physical activity with obesity has changed over time. METHODS: Dietary data from 36,377 U.S. adults from the National Health and Nutrition Survey (NHANES) between 1971 and 2008 was used. Physical activity frequency data was only available in 14,419 adults between 1988 and 2006. Generalised linear models were used to examine if the association between total caloric intake, percent dietary macronutrient intake and physical activity with body mass index (BMI) was different over time. RESULTS: Between 1971 and 2008, BMI, total caloric intake and carbohydrate intake increased 10-14%, and fat and protein intake decreased 5-9%. Between 1988 and 2006, frequency of leisure time physical activity increased 47-120%. However, for a given amount of caloric intake, macronutrient intake or leisure time physical activity, the predicted BMI was up to 2.3kg/m(2) higher in 2006 that in 1988 in the mutually adjusted model (P<0.05). CONCLUSIONS: Factors other than diet and physical activity may be contributing to the increase in BMI over time. Further research is necessary to identify these factors and to determine the mechanisms through which they affect body weight. KEYWORDS: Body mass index; Energy intake; Epidemiology; Etiology; NHANES
  12. Diet and risk of breast, endometrial and ovarian cancer: UK Women's Cohort Study. Dunneram Y, Greenwood DC, Cade JE. Br J Nutr. 2019 Sep 14;122(5):564-574. doi: 10.1017/S0007114518003665. Epub 2018 Dec 11. PMID: 30526696 Free Article Abstract This study aimed to investigate the association between diet and the risk of breast, endometrial and ovarian cancer in the UK Women's Cohort Study. A total of 35 372 women aged 35-69 years were enrolled between 1995 and 1998 and completed a validated 217-item FFQ. The individual foods were collapsed into sixty-four main food groups and compared using Cox proportional models, adjusting for potential confounders. Hazard ratio (HR) estimates are presented per portion increase in food items. After approximately 18 years of follow-up, there were 1822, 294 and 285 cases of breast, endometrial and ovarian cancer, respectively. A high consumption of processed meat and total meat was associated with an increased risk of breast and endometrial cancer. High intake of tomatoes (HR 0·87, 99 % CI 0·75, 1·00) and dried fruits (HR 0·60, 99 % CI 0·37, 0·97) was associated with a reduced risk of breast and endometrial cancer, respectively. Mushroom intake was associated with a higher risk of ovarian cancer (HR 1·57, 99 % CI 1·09, 2·26). Subgroup analysis by pre- or postmenopausal cancer further demonstrated an association between processed meat intake and both postmenopausal breast cancer and endometrial cancer. Intake of dried fruits was associated with a reduced risk of postmenopausal endometrial cancer (HR 0·55, 99 % CI 0·31, 0·98). Our findings suggest that while some foods may trigger the risk of these cancers, some foods may also be protective; supporting the call for further randomised controlled trials of dietary interventions to reduce the risk of cancer among pre- and postmenopausal women. KEYWORDS: Breast cancer; Diet; Endometrial cancer; Food groups; Ovarian cancer; Postmenopausal women; Premenopausal women Dietary Intake of Riboflavin and Unsaturated Fatty Acid Can Improve the Multi-Domain Cognitive Function in Middle-Aged and Elderly Populations: A 2-Year Prospective Cohort Study. Tao L, Liu K, Chen S, Yu H, An Y, Wang Y, Zhang X, Wang Y, Qin Z, Xiao R. Front Aging Neurosci. 2019 Aug 29;11:226. doi: 10.3389/fnagi.2019.00226. eCollection 2019. PMID: 31555120 Abstract OBJECTIVE: This study was aimed to explore the effects of dietary nutrients on cognitive function among the middle-aged and elderly populations. METHODS: A prospective cohort study of 1,385 middle-aged and elderly people was conducted from January 2014 to December 2017. Dietary nutrients were assessed according to the food frequency questionnaire (FFQ) and China Food Composition Database (CFCD). Montreal cognitive assessment (MoCA) was used to evaluate the participants' global cognitive function. Six other neuropsychological measures [auditory verbal learning test-immediate recall (AVLT-IR), auditory verbal learning test-short recall (AVLT-SR), auditory verbal learning test-long recall (AVLT-LR), logical memory test (LMT), digit span forward (DST-F), and digit span backward (DST-B)] were used to assess the verbal memory domain and the attention domain by principal component analysis (PCA). Multiple linear regressions were conducted to explore associations between nutrients and cognition. Sensitivity analyses were performed to confirm the results. RESULTS: Dietary riboflavin was protective for global cognitive function (β = 1.31, 95% CI: 0.26, 2.35) and the verbal memory domain (β = 0.37, 95% CI: 0.02, 0.71). Unsaturated fatty acid (USFA) played a protective role in global cognitive function (β = 1.15, 95% CI: 0.16, 2.14). The protective effects of riboflavin and USFA on cognitive function were consistent and reliable when different confounders were adjusted during sensitivity analyses. During the follow-up, neuropsychological measure scores revealed a reduced decline in the high-riboflavin group (d-MoCA, P = 0.025; d-AVLT-IR, P = 0.001; d-DST-B, P = 0.004; and d-composite score, P = 0.004) and the high-USFA group (d-AVLT-IR, P = 0.007; d-LMT, P = 0.032; d-DST-B, P = 0.002; and d-composite score, P = 0.008). CONCLUSION: Higher intake of riboflavin and USFA can improve multi-dimensional cognitive functioning in middle-aged and elderly people. These findings were consistent in different models of sensitivity analyses. KEYWORDS: cognitive impairment; dietary nutrients; middle-aged and elderly people; riboflavin; unsaturated fatty acid
  13. Is carrot consumption associated with a decreased risk of lung cancer? A meta-analysis of observational studies. Xu H, Jiang H, Yang W, Song F, Yan S, Wang C, Fu W, Li H, Lyu C, Gan Y, Lu Z. Br J Nutr. 2019 Sep 14;122(5):488-498. doi: 10.1017/S0007114519001107. PMID: 31552816 https://sci-hub.tw/10.1017/S0007114519001107 Abstract Findings of epidemiological studies regarding the association between carrot consumption and lung cancer risk remain inconsistent. The present study aimed to summarise the current epidemiological evidence concerning carrot intake and lung cancer risk with a meta-analysis. We conducted a meta-analysis of case-control and prospective cohort studies, and searched PubMed and Embase databases from their inception to April 2018 without restriction by language. We also reviewed reference lists from included articles. Prospective cohort or case-control studies reporting OR or relative risk with the corresponding 95 % CI of the risk lung cancer for the highest compared with the lowest category of carrot intake. A total of eighteen eligible studies (seventeen case-control studies and one prospective cohort study) were included, involving 202 969 individuals and 5517 patients with lung cancer. The pooled OR of eighteen studies for lung cancer was 0·58 (95 % CI 0·45, 0·74) by comparing the highest category with the lowest category of carrot consumption. Based on subgroup analyses for the types of lung cancer, we pooled that squamous cell carcinoma (OR 0·52, 95 % CI 0·19, 1·45), small-cell carcinoma (OR 0·43, 95 % CI 0·12, 1·59), adenocarcinoma (OR 0·34, 95 % CI 0·15, 0·79), large-cell carcinoma (OR 0·40, 95 % CI 0·10, 1·57), squamous and small-cell carcinoma (OR 0·85, 95 % CI 0·45, 1·62), adenocarcinoma and large-cell carcinoma (OR 0·20, 95 % CI 0·02, 1·70) and mixed types (OR 0·61, 95 % CI 0·46, 0·81). Exclusion of any single study did not materially alter the pooled OR. Integrated epidemiological evidence from observational studies supported the hypothesis that carrot consumption may decrease the risk of lung cancer, especially for adenocarcinoma. KEYWORDS: Cancer prevention; Carrot consumption; Epidemiology; Lung cancer Association of BCG Vaccination in Childhood With Subsequent Cancer Diagnoses: A 60-Year Follow-up of a Clinical Trial. Usher NT, Chang S, Howard RS, Martinez A, Harrison LH, Santosham M, Aronson NE. JAMA Netw Open. 2019 Sep 4;2(9):e1912014. doi: 10.1001/jamanetworkopen.2019.12014. PMID: 31553471 Abstract IMPORTANCE: The BCG vaccine is currently the only approved tuberculosis vaccine and is widely administered worldwide, usually during infancy. Previous studies found increased rates of lymphoma and leukemia in BCG-vaccinated populations. OBJECTIVE: To determine whether BCG vaccination was associated with cancer rates in a secondary analysis of a BCG vaccine trial. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review (60-year follow-up) of a clinical trial in which participants were assigned to the vaccine group by systematic stratification by school district, age, and sex, then randomized by alternation. The original study was conducted at 9 sites in 5 US states between December 1935 and December 1998. Participants were 2963 American Indian and Alaska Native schoolchildren younger than 20 years with no evidence of previous tuberculosis infection. Statistical analysis was conducted between August 2018 and July 2019. INTERVENTIONS: Single intradermal injection of either BCG vaccine or saline placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was diagnosis of cancer after BCG vaccination. Data on participant interval health and risk factors, including smoking, tuberculosis infection, isoniazid use, and other basic demographic information, were also collected. RESULTS: A total of 2963 participants, including 1540 in the BCG vaccine group and 1423 in the placebo group, remained after exclusions. Vaccination occurred at a median (interquartile range) age of 8 (5-11) years; 805 participants (52%) in the BCG group and 710 (50%) in the placebo group were female. At the time of follow-up, 97 participants (7%) in the placebo group and 106 participants (7%) in the BCG vaccine group could not be located; total mortality was 633 participants (44%) in the placebo group and 632 participants (41%) in the BCG group. The overall rate of cancer diagnosis was not significantly different in BCG vaccine vs placebo recipients (hazard ratio, 0.82; 95% CI, 0.66-1.02), including for lymphoma and leukemia. The rate of lung cancer was significantly lower in BCG vs placebo recipients (18.2 vs 45.4 cases per 100 000 person-years; hazard ratio, 0.38; 95% CI, 0.20-0.74; P = .005), controlling for sex, region, alcohol overuse, smoking, and tuberculosis. CONCLUSIONS AND RELEVANCE: Childhood BCG vaccination was associated with a lower risk of lung cancer development in American Indian and Alaska Native populations. This finding has potentially important health implications given the high mortality rate associated with lung cancer and the availability of low-cost BCG vaccines.
  14. How an Ice Bath May Undermine Your Weight Workout Cold water immersion is popular with some athletes, but it may slow the growth of new muscle. https://www.nytimes.com/2019/09/25/well/move/weights-muscles-cold-ice-bath-weightlifting-exercise-recovery.html?fallback=0&recId=1RNg6bFSRSnrmDsHpSiBRa8mENW&locked=0&geoContinent=NA&geoRegion=SK&recAlloc=control&geoCountry=CA&blockId=home-discovery-vi-prg&imp_id=622554476 >>>>>>>>>>>>>>>>> Cold water immersion attenuates anabolic signalling and skeletal muscle fiber hypertrophy, but not strength gain, following whole-body resistance training. Fyfe JJ, Broatch JR, Trewin AJ, Hanson ED, Argus CK, Garnham AP, Halson SL, Polman RC, Bishop DJ, Petersen AC. J Appl Physiol (1985). 2019 Sep 12. doi: 10.1152/japplphysiol.00127.2019. [Epub ahead of print] PMID: 31513450 Abstract Purpose: We determined the effects of CWI on long-term adaptations and post-exercise molecular responses in skeletal muscle before and after resistance training. Methods: Sixteen males (22.9 ± 4.6 y; 85.1 ± 17.9 kg; mean ± SD) performed resistance training (3 d·wk-1) for 7 wk, with each session followed by either CWI (15 min at 10°C, COLD group, n = 8 or passive recovery (15 min at 23°C, CON group, n = 8). Exercise performance [one-repetition maximum (1-RM) leg press and bench press, countermovement jump, squat jump and ballistic push-up], body composition (dual x-ray absorptiometry), and post-exercise (i.e., +1 and +48 h) molecular responses were assessed before and after training. Results: Improvements in 1-RM leg press were similar between groups [130 ±69 kg, pooled effect size (ES): 1.53; ±90% confidence interval (CI) 0.49], while increases in type II muscle fiber cross-sectional area were attenuated with CWI (-1959 µM2; ±1675; ES: -1.37; ±0.99). Post-exercise mTORC1 signalling (rps6 phosphorylation) was blunted for COLD at POST +1 h (-0.4-fold, ES: -0.69; ±0.86) and POST +48 h (-0.2-fold, ES: -1.33; ±0.82), while basal protein degradation markers (FOX-O1 protein content) were increased (1.3-fold, ES: 2.17; ±2.22). Training-induced increases in HSP27 protein content were attenuated for COLD (-0.8-fold, ES, -0.94 ±0.82), which also reduced total HSP72 protein content (-0.7-fold, ES: -0.79, ±0.57). Conclusion: CWI blunted resistance training-induced muscle fiber hypertrophy, but not maximal strength, potentially via reduced skeletal muscle protein anabolism and increased catabolism. Post-exercise CWI should therefore be avoided if muscle hypertrophy is desired.
  15. Some tea bags may shed billions of microplastics per cup 'Silken' bags for premium teas are made of PET or nylon, but it's not known if that poses health risk Emily Chung · CBC News https://www.cbc.ca/news/technology/tea-bags-plastic-study-mcgill-1.5295662 Associations of vigorous physical activity with all-cause, cardiovascular and cancer mortality among 64 913 adults. Rey Lopez JP, Gebel K, Chia D, Stamatakis E. BMJ Open Sport Exerc Med. 2019 Aug 12;5(1):e000596. doi: 10.1136/bmjsem-2019-000596. eCollection 2019. PMID: 31548909 Abstract BACKGROUND: Physical activity recommendations state that for the same energy expenditure, moderate-to-vigorous physical activities (MVPAs) produce similar health benefits. However, few epidemiological studies have tested this hypothesis. DESIGN: We examined whether, compared with moderate, vigorous activity was associated with larger mortality risk reductions. METHODS: Data from 11 cohorts of the Health Survey for England and the Scottish Health Survey, collected from 1994 to 2011 (mean (SD) follow-up, 9.0 (3.6) years). Adults aged ≥30 years reported MVPA and linkage to mortality records. Exposure was the proportion of self-reported weighted MVPA through vigorous activity. Outcomes were all-cause, cardiovascular disease (CVD) and cancer mortality. RESULTS: Among 64 913 adult respondents (44% men, 56% women, mean (SD) age, 49.8 (13.6) years), there were 5064 deaths from all-causes, 1393 from CVD and 1602 from cancer during 435 743 person-years of follow-up. Compared with those who reported no vigorous physical activity, and holding constant the volume of weighted MVPA, vigorous activity was associated with additional reductions in mortality risk. For all-cause mortality, the adjusted HR was HR=0.84 (95% CI 0.71, 0.99) and HR=0.84 (95% CI 0.76, 0.94) among those who reported between >0% and<30%, or ≥30% of their activity as vigorous, respectively. For CVD and cancer mortality, point estimates showed similar beneficial associations yet CIs were wider and crossed unity. CONCLUSION: Vigorous activities were associated with larger reductions in mortality risk than activities of moderate intensity, but no evidence of dose-response effects was found. KEYWORDS: cardio-protection; exercise; longevity; non-communicable diseases; physical activity