In Europe and the US, Higher Vitamin D Levels Reduce Risk of Mortality
Just last week, we published a blog on how higher vitamin D levels were associated with better survival rates in women with breast cancer. Now a meta-analysis of 8 studies in Europe and the US by Schöttker et al has also found 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. How did they reach these conclusions?
The authors used individual patient level data for their meta-analysis. This means that information about each individual in each study was pooled, which helps the authors to reduce differences between studies, and allows them to conduct analyses not reported in study-level data. For example, the ages of participants in each study varied, but by using the individual subject data, the authors could restrict the results to subjects aged 50-79, therefore reducing the chance that differences in mortality rates were due to differences in the age range used for each study.
The studies were conducted in the US and several European countries including France, Germany, Norway, Poland, the Czech Republic and Lithuania. In total, around 26,000 participants were included in the analysis, follow-up occurred over 4 to 12 years, and there were 6,700 deaths during the study period. Data from SENECA, NHANES, MONICA/KORA (information in German), Tromsø, and the HAPIEE study were included. International coding was used to establish cause of death in each study.
The authors found that people with the lowest 20% of vitamin D levels had a 1.6 times increased mortality compared to people in the top 20%. Specifically, cardiovascular mortality was 1.4 times higher and cancer mortality for people with a history of cancer was 1.7 times higher in subjects with the lowest vitamin D levels. There appeared to be a dose response, in that the highest mortality was found in people with the lowest vitamin D levels, and mortality rate decreased as vitamin D levels rose. All these results were consistent regardless of the study population used, sex, age, and season of blood draw.
These results are from epidemiological studies. This means that causation cannot be shown. It is possible that factors such as ill health reducing the amount of time spent outside in the sun is the cause of the association. Even so, the consistency of the association is important, especially in light of other articles showing that low vitamin D levels increase mortality risk, such as these meta-analyses from Chowdhury and Yin. Current recommendations make use of evidence showing that vitamin D deficiency is associated with higher risk of osteoporosis and bone fractures. Schöttker and associates showed that deficient levels of vitamin D were additionally associated with increased mortality risk from other causes. The authors stress the public health importance that reducing rates of all-cause mortality can have and recommend that people avoid vitamin D deficiency.
Schöttker B, Jorde R, Peasey A, Thorand B, Jansen EHJM, Groot LD, 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. http://dx.doi.org/10.1136/bmj.g3656
Chowdhury R, Kunutsor S, Vitezova A, et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. 2014 BMJ doi: 10.1136/bmj.g1903
Schöttker B, Haug U, Schomburg L, Köhrle J, Perna L, Müller H, 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 Nutr2013;97:782-93. http://www.ncbi.nlm.nih.gov/pubmed/23446902
Yin L, Ordóñez-Mena JM, Chen T, Schöttker B, Arndt V, Brenner H. Circulating 25-hydroxyvitamin D serum concentration and total cancer incidence and mortality: a systematic review and meta-analysis. Prev Med2013;57:753-64. doi: 10.1016/j.ypmed.2013.08.026