ObjectiveTo investigate the association of predicted lean body mass, fat mass, and body mass index (BMI) with all cause and cause specific mortality in men.DesignProspective cohort study.SettingHealth professionals in the United StatesParticipants38 006 men (aged 40-75 years) from the Health Professionals Follow-up Study, followed up for death (1987-2012).Main outcome measuresAll cause and cause specific mortality.ResultsUsing validated anthropometric prediction equations previously developed from the National Health and Nutrition Examination Survey, lean body mass and fat mass were estimated for all participants. During a mean of 21.4 years of follow-up, 12 356 deaths were identified. A J shaped association was consistently observed between BMI and all cause mortality. Multivariable adjusted Cox models including predicted fat mass and lean body mass showed a strong positive monotonic association between predicted fat mass and all cause mortality. Compared with those in the lowest fifth of predicted fat mass, men in the highest fifth had a hazard ratio of 1.35 (95% confidence interval 1.26 to 1.46) for mortality from all causes. In contrast, a U shaped association was found between predicted lean body mass and all cause mortality. Compared with those in the lowest fifth of predicted lean body mass, men in the second to fourth fifths had 8-10% lower risk of mortality from all causes. In the restricted cubic spline models, the risk of all cause mortality was relatively flat until 21 kg of predicted fat mass and increased rapidly afterwards, with a hazard ratio of 1.22 (1.18 to 1.26) per standard deviation. For predicted lean body mass, a large reduction of the risk was seen within the lower range until 56 kg, with a hazard ratio of 0.87 (0.82 to 0.92) per standard deviation, which increased thereafter (P for non-linearity <0.001). For cause specific mortality, men in the highest fifth of predicted fat mass had hazard ratios of 1.67 (1.47 to 1.89) for cardiovascular disease, 1.24 (1.09 to 1.43) for cancer, and 1.26 (0.97 to 1.64) for respiratory disease. On the other hand, a U shaped association was found between predicted lean body mass and mortality from cardiovascular disease and cancer. However, a strong inverse association existed between predicted lean body mass and mortality from respiratory disease (P for trend <0.001).ConclusionsThe shape of the association between BMI and mortality was determined by the relation between two body components (lean body mass and fat mass) and mortality. This finding suggests that the “obesity paradox” controversy may be largely explained by low lean body mass, rather than low fat mass, in the lower range of BMI.

Background: Previous meta-analyses of randomized controlled trials (RCTs) of vitamin D supplementation and total cancer incidence and mortality found inconsistent results, and most included trials administered generally low doses of vitamin D (1100 IU/day). We updated the meta-analysis by incorporating recent RCTs that have tested higher doses of vitamin D supplements.Materials and methods: PubMed and Embase were searched from the inception to November 2018. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a random-effects model. Results: For total cancer incidence, 10 trials were included [6537 cases; 3-10 years of follow-up; 54-135 nmol/l of attained levels of circulating 25(OH) vitamin D [25(OH)D] in the intervention group]. The summary RR was 0.98 (95% CI, 0.93-1.03; P ¼ 0.42; I 2 ¼ 0%). The results remained null across subgroups tested, including even when attained 25(OH)D levels exceeded 100 nmol/l (RR, 0.95; 95% CI, 0.83-1.09; P ¼ 0.48; I 2 ¼ 26%). For total cancer mortality, five trials were included [1591 deaths; 3-10 years of follow-up; 54-135 nmol/l of attained levels of circulating 25(OH)D in the intervention group]. The summary RR was 0.87 (95% CI, 0.79-0.96; P ¼ 0.005; I 2 ¼ 0%), which was largely attributable to interventions with daily dosing (as opposed to infrequent bolus dosing). No statistically significant heterogeneity was observed by attained levels of circulating 25(OH)D (P heterogeneity ¼ 0.83), with RR being 0.88 (95% CI, 0.78-0.98; P ¼ 0.02; I 2 ¼ 0%) for 100 nmol/l and 0.85 (95% CI, 0.70-1.03; P ¼ 0.11; I 2 ¼ 0%) for >100 nmol/l. Conclusions:In an updated meta-analysis of RCTs, vitamin D supplementation significantly reduced total cancer mortality but did not reduce total cancer incidence.

Avoiding adult weight gain itself may confer protection against certain types of cancers, particularly among HRT nonusers.