Vitamin D and Mortality
Vitamin D and Mortality
Objective To investigate the association between serum 25-hydroxyvitamin D concentrations (25(OH)D) and mortality in a large consortium of cohort studies paying particular attention to potential age, sex, season, and country differences.
Design Meta-analysis of individual participant data of eight prospective cohort studies from Europe and the US.
Setting General population.
Participants 26 018 men and women aged 50-79 years
Main outcome measures All-cause, cardiovascular, and cancer mortality.
Results 25(OH)D concentrations varied strongly by season (higher in summer), country (higher in US and northern Europe) and sex (higher in men), but no consistent trend with age was observed. During follow-up, 6695 study participants died, among whom 2624 died of cardiovascular diseases and 2227 died of cancer. For each cohort and analysis, 25(OH)D quintiles were defined with cohort and subgroup specific cut-off values. Comparing bottom versus top quintiles resulted in a pooled risk ratio of 1.57 (95% CI 1.36 to 1.81) for all-cause mortality. Risk ratios for cardiovascular mortality were similar in magnitude to that for all-cause mortality in subjects both with and without a history of cardiovascular disease at baseline. With respect to cancer mortality, an association was only observed among subjects with a history of cancer (risk ratio, 1.70 (1.00 to 2.88)). Analyses using all quintiles suggest curvilinear, inverse, dose-response curves for the aforementioned relationships. No strong age, sex, season, or country specific differences were detected. Heterogeneity was low in most meta-analyses.
Conclusions Despite levels of 25(OH)D strongly varying with country, sex, and season, the association between 25(OH)D level and all-cause and cause-specific mortality was remarkably consistent. Results from a long term randomised controlled trial addressing longevity are being awaited before vitamin D supplementation can be recommended in most individuals with low 25(OH)D levels.
Although vitamin D is obtained from diet and dietary supplements, the main source of vitamin D is its production in skin under the influence of solar ultraviolet B radiation. The most commonly measured vitamin D metabolite is serum 25-hydroxyvitamin D (25(OH)D) because of its greater half life (~3 weeks) and up to 1000-fold higher serum levels compared with the physiologically active metabolite 1,25-dihydroxyvitamin D (half life of a few hours). As ultraviolet B exposure varies with the latitude of regions and during the year, so mean 25(OH)D concentrations of populations also vary accordingly. Furthermore, women are generally more prone to low 25(OH)D concentrations than men (possibly because of a positive correlation of 25(OH)D with testosterone levels), and vitamin D deficiency is especially common among elderly people, who often have less sun exposure (because of reduced outdoor activity) and limited capacity of the skin to produce vitamin D metabolites. However, it is unclear if and to what extent these influences on production and maintenance of sufficient vitamin D metabolite concentrations affect the prognostic association of low 25(OH)D concentrations with mortality.
The objective of this meta-analysis of a consortium of eight prospective cohort studies from different European countries and the United States was to investigate the prognostic association of 25(OH)D measurements with all-cause, cardiovascular, and cancer mortality, paying particular attention to potential differences between countries, sexes, age groups, and seasons of blood draw.
Abstract and Introduction
Abstract
Objective To investigate the association between serum 25-hydroxyvitamin D concentrations (25(OH)D) and mortality in a large consortium of cohort studies paying particular attention to potential age, sex, season, and country differences.
Design Meta-analysis of individual participant data of eight prospective cohort studies from Europe and the US.
Setting General population.
Participants 26 018 men and women aged 50-79 years
Main outcome measures All-cause, cardiovascular, and cancer mortality.
Results 25(OH)D concentrations varied strongly by season (higher in summer), country (higher in US and northern Europe) and sex (higher in men), but no consistent trend with age was observed. During follow-up, 6695 study participants died, among whom 2624 died of cardiovascular diseases and 2227 died of cancer. For each cohort and analysis, 25(OH)D quintiles were defined with cohort and subgroup specific cut-off values. Comparing bottom versus top quintiles resulted in a pooled risk ratio of 1.57 (95% CI 1.36 to 1.81) for all-cause mortality. Risk ratios for cardiovascular mortality were similar in magnitude to that for all-cause mortality in subjects both with and without a history of cardiovascular disease at baseline. With respect to cancer mortality, an association was only observed among subjects with a history of cancer (risk ratio, 1.70 (1.00 to 2.88)). Analyses using all quintiles suggest curvilinear, inverse, dose-response curves for the aforementioned relationships. No strong age, sex, season, or country specific differences were detected. Heterogeneity was low in most meta-analyses.
Conclusions Despite levels of 25(OH)D strongly varying with country, sex, and season, the association between 25(OH)D level and all-cause and cause-specific mortality was remarkably consistent. Results from a long term randomised controlled trial addressing longevity are being awaited before vitamin D supplementation can be recommended in most individuals with low 25(OH)D levels.
Introduction
Although vitamin D is obtained from diet and dietary supplements, the main source of vitamin D is its production in skin under the influence of solar ultraviolet B radiation. The most commonly measured vitamin D metabolite is serum 25-hydroxyvitamin D (25(OH)D) because of its greater half life (~3 weeks) and up to 1000-fold higher serum levels compared with the physiologically active metabolite 1,25-dihydroxyvitamin D (half life of a few hours). As ultraviolet B exposure varies with the latitude of regions and during the year, so mean 25(OH)D concentrations of populations also vary accordingly. Furthermore, women are generally more prone to low 25(OH)D concentrations than men (possibly because of a positive correlation of 25(OH)D with testosterone levels), and vitamin D deficiency is especially common among elderly people, who often have less sun exposure (because of reduced outdoor activity) and limited capacity of the skin to produce vitamin D metabolites. However, it is unclear if and to what extent these influences on production and maintenance of sufficient vitamin D metabolite concentrations affect the prognostic association of low 25(OH)D concentrations with mortality.
The objective of this meta-analysis of a consortium of eight prospective cohort studies from different European countries and the United States was to investigate the prognostic association of 25(OH)D measurements with all-cause, cardiovascular, and cancer mortality, paying particular attention to potential differences between countries, sexes, age groups, and seasons of blood draw.
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