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The most commonly measured vitamin D metabolite is 25-hydroxyvitamin D (25(OH)D) because of its longer half-life (~3 weeks) and higher serum levels (up to 1000-fold higher than the other physiologically active metabolite; 1,25-dihydroxyvitamin D).1 Concentrations of 25(OH)D vary by age, sex, season, education, obesity, physical activity, and smoking. Low levels of the vitamin have been associated with numerous health problems, such as increased risk of death from cardiovascular disease (CVD), higher risk of cognitive impairment in later life and increased risk of asthma among children and patients with cancer.2 Evidence from observational studies do suggest inverse relationship of circulating 25-hydroxyvitamin D and risks of death due to cardiovascular disease, cancer, and other causes.3

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A recently published meta-analysis of prospective cohort studies, which included 26,018 men and women, showed that vitamin D deficiency may be more harmful than we think.4  The study included participants in the US and several European countries including France, Germany, Norway, Poland, the Czech Republic and Lithuania. Follow-up occurred over 4 to 12 years, and there were 6,700 deaths during the study period. Among those who died,  2624 died of CVD and  2227 died of cancer. Mortality was 1.6 times higher in participants with the lowest 20% of vitamin D levels compared to people in the top 20%. Cardiovascular mortality was 1.4 times higher and cancer mortality for people with a history of cancer was 1.7 times higher in those subjects with lowest vitamin D levels. Furthermore, mortality rate decreased as vitamin D levels rose.

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These results suggest that there are lower rates of all-cause mortality in subjects with the highest levels of vitamin D. For cancer deaths, higher vitamin D levels protected against people with a history of cancer. It shall be noted that these results were compiled from epidemiological studies and therefore causation can not be shown. 

1. Zerwekh JE. Blood biomarkers of vitamin D status. Am J Clin Nutr 2008;87:1087S-91S   [PubMed: 18400739]
2. Schöttker B, Haug U, Schomburg L, Köhrle J, et al. Strong associations of 25-hydroxyvitamin D concentrations with all-cause, cardiovascular, cancer, and respiratory disease mortality in a large cohort study. Am J Clin Nutr 2013;97:782-93.   [PubMed: 23446902]
3. Chowdhury R, Kunutsor S, Vitezova A, Oliver-Williams C, et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ 2014;348:g1903 DOI: 10.1136/bmj.g1903
4. Schöttker B, Jorde R, Peasey A, Thorand B, et al. Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States. BMJ 2014;348:g3656 doi: 10.1136/bmj.g3656 (Published 17 June 2014)

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