Non-occupational physical activity and risk of cardiovascular disease, cancer and mortality outcomes: a dose-response meta-analysis of large prospective studies.

OBJECTIVE: To estimate the dose-response associations between non-occupational physical activity and several chronic disease and mortality outcomes in the general adult population. DESIGN: Systematic review and cohort-level dose-response meta-analysis. DATA SOURCES: PubMed, Scopus, Web of Science and reference lists of published studies. ELIGIBILITY CRITERIA: Prospective cohort studies with (1) general population samples >10 000 adults, (2) ≥3 physical activity categories, and (3) risk measures and CIs for all-cause mortality or incident total cardiovascular disease, coronary heart disease, stroke, heart failure, total cancer and site-specific cancers (head and neck, myeloid leukaemia, myeloma, gastric cardia, lung, liver, endometrium, colon, breast, bladder, rectum, oesophagus, prostate, kidney). RESULTS: 196 articles were included, covering 94 cohorts with >30 million participants. The evidence base was largest for all-cause mortality (50 separate results; 163 415 543 person-years, 811 616 events), and incidence of cardiovascular disease (37 results; 28 884 209 person-years, 74 757 events) and cancer (31 results; 35 500 867 person-years, 185 870 events). In general, higher activity levels were associated with lower risk of all outcomes. Differences in risk were greater between 0 and 8.75 marginal metabolic equivalent of task-hours per week (mMET-hours/week) (equivalent to the recommended 150 min/week of moderate-to-vigorous aerobic physical activity), with smaller marginal differences in risk above this level to 17.5 mMET-hours/week, beyond which additional differences were small and uncertain. Associations were stronger for all-cause (relative risk (RR) at 8.75 mMET-hours/week: 0.69, 95% CI 0.65 to 0.73) and cardiovascular disease (RR at 8.75 mMET-hours/week: 0.71, 95% CI 0.66 to 0.77) mortality than for cancer mortality (RR at 8.75 mMET-hours/week: 0.85, 95% CI 0.81 to 0.89). If all insufficiently active individuals had achieved 8.75 mMET-hours/week, 15.7% (95% CI 13.1 to 18.2) of all premature deaths would have been averted. CONCLUSIONS: Inverse non-linear dose-response associations suggest substantial protection against a range of chronic disease outcomes from small increases in non-occupational physical activity in inactive adults. PROSPERO registration number CRD42018095481.

Is occupational physical activity associated with mortality in UK Biobank?

BACKGROUND: Current physical activity guidelines do not distinguish between activity accumulated in different behavioural domains but some studies suggest that occupational physical activity (OPA) may not confer health benefits and could even be detrimental. The purpose of this study was to investigate associations between OPA and mortality outcomes. METHODS: From baseline (2006-2010), 460,901 UK Biobank participants (aged 40-69 years) were followed for a median 12.0 (IQR: 11.3-12.7) years. OPA was categorised by cross-tabulating degree of manual work and walking/standing work amongst those in paid employment (n = 267,765), and combined with categories of occupational status for those not in paid employment (n = 193,136). Cox proportional hazards models were used to estimate sex-stratified hazard ratios (HR) and 95% confidence intervals (CI) for mortality from all causes, CVD, and cancer by occupational group, and for working hours/week and non-occupational physical activity stratified by occupational group. Models included adjustment for age and a range of lifestyle, socio-economic and health-related covariates. RESULTS: During 5,449,989 person-years of follow-up, 28,740 deaths occurred. Compared to those reporting no heavy manual or walking/standing work (e.g. sedentary office workers) and adjusting for covariates, retirement was associated with lower mortality in women (HR = 0.62, CI: 0.53-0.72) and men (HR = 0.80, CI: 0.71-0.90), whereas unemployment was associated with higher mortality in men only (HR = 1.24, CI: 1.07-1.45). Within the working population, there was no evidence of differences in all-cause, CVD or cancer mortality by OPA group when comparing those reporting higher levels of OPA to the lowest OPA reference group for both women and men. Working < 35 h/week versus 35-40 h/week was associated with lower mortality in women (HR = 0.85, CI: 0.79-0.92) and men (HR = 0.83, CI: 0.78-0.89), with no interaction by OPA. Non-occupational physical activity was associated with lower mortality in working women (HR = 0.89 per 5 kJ/day/kg, CI: 0.84-0.95) and men (HR = 0.87 per 5 kJ/day/kg, CI: 0.84-0.91), with no interaction by OPA group. CONCLUSIONS: Jobs classified as higher levels of OPA may not be as active as reported, or the types of physical activity performed in those jobs are not health-enhancing. Irrespective of OPA category or employment status, non-occupational physical activity appears to provide health benefits.

Postprandial changes in cardiometabolic disease risk in young Chinese men following isocaloric high or low protein diets, stratified by either high or low meal frequency - a randomized controlled crossover trial.

BACKGROUND: Cardio-Metabolic Disease (CMD) is the leading cause of death globally and particularly in Asia. Postprandial elevation of glycaemia, insulinaemia, triglyceridaemia are associated with an increased risk of CMD. While studies have shown that higher protein intake or increased meal frequency may benefit postprandial metabolism, their combined effect has rarely been investigated using composite mixed meals. We therefore examined the combined effects of increasing meal frequency (2-large vs 6-smaller meals), with high or low-protein (40 % vs 10 % energy from protein respectively) isocaloric mixed meals on a range of postprandial CMD risk markers. METHODS: In a randomized crossover study, 10 healthy Chinese males (Age: 29 ± 7 years; BMI: 21.9 ± 1.7 kg/m(2)) underwent 4 dietary treatments: CON-2 (2 large Low-Protein meals), CON-6 (6 Small Low-Protein meals), PRO-2 (2 Large High-Protein meals) and PRO-6 (6 Small High-Protein meals). Subjects wore a continuous glucose monitor (CGM) and venous blood samples were obtained at baseline and at regular intervals for 8.5 h to monitor postprandial changes in glucose, insulin, triglycerides and high sensitivity C-reactive protein (hsCRP). Blood pressure was measured at regular intervals pre- and post- meal consumption. Urine was collected to measure excretion of creatinine and F2-isoprostanes and its metabolites over the 8.5 h postprandial period. RESULTS: The high-protein meals, irrespective of meal frequency were beneficial for glycaemic health since glucose incremental area under the curve (iAUC) for PRO-2 (185 ± 166 mmol.min.L(-1)) and PRO-6 (214 ± 188 mmol.min.L(-1)) were 66 and 60 % lower respectively (both p < 0.05), compared with CON-2 (536 ± 290 mmol.min.L(-1)). The iAUC for insulin was the lowest for PRO-6 (13.7 ± 7.1 U.min.L(-1)) as compared with CON-2 (28.4 ± 15.6 U.min.L(-)1), p < 0.001. There were no significant differences in postprandial responses in other measurements between the dietary treatments. CONCLUSIONS: The consumption of composite meals with higher protein content, irrespective of meal frequency appears to be beneficial for postprandial glycemic and insulinemic responses in young, healthy Chinese males. Implications of this study may be useful in the Asian context where the consumption of high glycemic index, carbohydrate meals is prevalent. TRIAL REGISTRATION: NCT02529228 .

Effect of sprint interval versus continuous cycling on postprandial lipaemia.

The present study compares the effect of a single bout of sprint interval cycling against continuous cycling on postprandial lipaemia. Participants were nine healthy volunteers (five male), aged 20-26 years. Each participant undertook three 2-d trials in a random order. On day 1, participants rested (control), undertook a single 20 minute bout of continuous cycling at 70% of maximum oxygen uptake or completed four 30-second bouts of sprint interval cycling on a cycle ergometer, separated by 4.5 minutes of recovery. On day 2, participants rested and consumed a test meal (75% fat). Triacylglycerol concentrations were measured fasting and for 6 hours after the meal. The total area under the triacylglycerol concentration against time curve was similar among trials (mean (SD): control, 9.51 (3.50) mmol · l(-1) compared with continuous cycling, 8.58 (3.08) mmol · l(-1) compared with sprint interval cycling, 9.28 (1.89) mmol · l(-1); P = 0.517). There was no difference in the pattern of TAG response to the test meal among trials (trial × time interaction, P = 0.637). The present study found no effect of sprint interval or continuous cycling on postprandial lipaemia, with the reason for this finding unclear. Future studies need to more precisely determine the relationship between exercise and postprandial lipaemia across different types of exercise.

Association Between Physical Activity and Risk of Depression: A Systematic Review and Meta-analysis.

Importance: Depression is the leading cause of mental health-related disease burden and may be reduced by physical activity, but the dose-response relationship between activity and depression is uncertain. Objective: To systematically review and meta-analyze the dose-response association between physical activity and incident depression from published prospective studies of adults. Data Sources: PubMed, SCOPUS, Web of Science, PsycINFO, and the reference lists of systematic reviews retrieved by a systematic search up to December 11, 2020, with no language limits. The date of the search was November 12, 2020. Study Selection: We included prospective cohort studies reporting physical activity at 3 or more exposure levels and risk estimates for depression with 3000 or more adults and 3 years or longer of follow-up. Data Extraction and Synthesis: Data extraction was completed independently by 2 extractors and cross-checked for errors. A 2-stage random-effects dose-response meta-analysis was used to synthesize data. Study-specific associations were estimated using generalized least-squares regression and the pooled association was estimated by combining the study-specific coefficients using restricted maximum likelihood. Main Outcomes and Measures: The outcome of interest was depression, including (1) presence of major depressive disorder indicated by self-report of physician diagnosis, registry data, or diagnostic interviews and (2) elevated depressive symptoms established using validated cutoffs for a depressive screening instrument. Results: Fifteen studies comprising 191 130 participants and 2 110 588 person-years were included. An inverse curvilinear dose-response association between physical activity and depression was observed, with steeper association gradients at lower activity volumes; heterogeneity was large and significant (I2 = 74%; P < .001). Relative to adults not reporting any activity, those accumulating half the recommended volume of physical activity (4.4 marginal metabolic equivalent task hours per week [mMET-h/wk]) had 18% (95% CI, 13%-23%) lower risk of depression. Adults accumulating the recommended volume of 8.8 mMET hours per week had 25% (95% CI, 18%-32%) lower risk with diminishing potential benefits and higher uncertainty observed beyond that exposure level. There were diminishing additional potential benefits and greater uncertainty at higher volumes of physical activity. Based on an estimate of exposure prevalences among included cohorts, if less active adults had achieved the current physical activity recommendations, 11.5% (95% CI, 7.7%-15.4%) of depression cases could have been prevented. Conclusions and Relevance: This systematic review and meta-analysis of associations between physical activity and depression suggests significant mental health benefits from being physically active, even at levels below the public health recommendations. Health practitioners should therefore encourage any increase in physical activity to improve mental health.

Estimating the impact of achieving Turkey's non-communicable disease policy targets: A macro-simulation modelling study.

BACKGROUND: The Burden of non-communicable disease (NCDs) has continued to rise globally, particularly in low- and middle-income countries. In Turkey, NCDs account for 89% of all deaths, with nearly one in five deaths occurring before age 70. This study investigates the number of NCD deaths that could be prevented if Turkey met national and international targets for major modifiable NCD risk factors. METHODS: Preventable deaths were estimated using the World Health Organization (WHO) 'Preventable Risk Integrated ModEl' (PRIME), by combining: 1) Baseline exposure data for risk factors, referenced from national surveillance and cohort studies; 2) Aetiological associations from published meta-analyses; and 3) Demographic and mortality statistics obtained from the Turkish Statistical Institute (TurkStat). Confidence intervals were estimated using Monte Carlo simulations. FINDINGS: If Turkey met its NCD risk factor targets for reducing tobacco and salt consumption by 30%, and physical inactivity by 10% in 2017, an estimated 19,859 deaths (95%CI: 12,802 to 26,609) could have been prevented. Approximately two thirds of these preventable deaths were in men, and one in three were in adults below 75 years. A 30% relative reduction in the consumption of alcohol, tobacco, and salt, as well as physical inactivity, would prevent 180 (107 to 259); 4,786 (3,679 to 5,836); 13,112 (5,819 to 19,952); and 7,124 (5,053 to 9,212) deaths, respectively. INTERPRETATION: Among major modifiable NCD risk factors, population-level reductions in salt intake and physical inactivity present the greatest opportunity for reducing NCD mortality in Turkey. These findings can help Turkey prioritise interventions to meet the Sustainable Development Goal target of reducing NCD mortality by one third, by 2030.

Physical activity trajectories and mortality: population based cohort study.

OBJECTIVE: To assess the prospective associations of baseline and long term trajectories of physical activity on mortality from all causes, cardiovascular disease, and cancer. DESIGN: Population based cohort study. SETTING: Adults from the general population in the UK. PARTICIPANTS: 14 599 men and women (aged 40 to 79) from the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort, assessed at baseline (1993 to 1997) up to 2004 for lifestyle and other risk factors; then followed to 2016 for mortality (median of 12.5 years of follow-up, after the last exposure assessment). MAIN EXPOSURE: Physical activity energy expenditure (PAEE) derived from questionnaires, calibrated against combined movement and heart rate monitoring. MAIN OUTCOME MEASURES: Mortality from all causes, cardiovascular disease, and cancer. Multivariable proportional hazards regression models were adjusted for age, sex, sociodemographics, and changes in medical history, overall diet quality, body mass index, blood pressure, triglycerides, and cholesterol levels. RESULTS: During 171 277 person years of follow-up, 3148 deaths occurred. Long term increases in PAEE were inversely associated with mortality, independent of baseline PAEE. For each 1 kJ/kg/day per year increase in PAEE (equivalent to a trajectory of being inactive at baseline and gradually, over five years, meeting the World Health Organization minimum physical activity guidelines of 150 minutes/week of moderate-intensity physical activity), hazard ratios were: 0.76 (95% confidence interval 0.71 to 0.82) for all cause mortality, 0.71 (0.62 to 0.82) for cardiovascular disease mortality, and 0.89 (0.79 to 0.99) for cancer mortality, adjusted for baseline PAEE, and established risk factors. Similar results were observed when analyses were stratified by medical history of cardiovascular disease and cancer. Joint analyses with baseline and trajectories of physical activity show that, compared with consistently inactive individuals, those with increasing physical activity trajectories over time experienced lower risks of mortality from all causes, with hazard ratios of 0.76 (0.65 to 0.88), 0.62 (0.53 to 0.72), and 0.58 (0.43 to 0.78) at low, medium, and high baseline physical activity, respectively. At the population level, meeting and maintaining at least the minimum physical activity recommendations would potentially prevent 46% of deaths associated with physical inactivity. CONCLUSIONS: Middle aged and older adults, including those with cardiovascular disease and cancer, can gain substantial longevity benefits by becoming more physically active, irrespective of past physical activity levels and established risk factors. Considerable population health impacts can be attained with consistent engagement in physical activity during mid to late life.

A phenotypic screening platform to identify small molecule modulators of Chlamydomonas reinhardtii growth, motility and photosynthesis.

Chemical biology, the interfacial discipline of using small molecules as probes to investigate biology, is a powerful approach of developing specific, rapidly acting tools that can be applied across organisms. The single-celled alga Chlamydomonas reinhardtii is an excellent model system because of its photosynthetic ability, cilia-related motility and simple genetics. We report the results of an automated fitness screen of 5,445 small molecules and subsequent assays on motility/phototaxis and photosynthesis. Cheminformatic analysis revealed active core structures and was used to construct a naïve Bayes model that successfully predicts algal bioactive compounds.