There is a vast quantity of observational vitamin D literature investigating its use in various chronic diseases eg bone mineral disease, autoimmunity, cancer, diabetes, and cardiovascular outcomes. However interpretation of this data is complex and is further complicated by the numerous media reports suggesting it as a panacea for chronic disease.
The BMJ has featured two systematic reviews which attempt to interpret the existing data but using different approaches.
Theodoratou et al (current systematic review) highlight differences between observational data (relating circulating 25-hydroxyvitamin D to outcomes) and RCTs of supplementation. Of 137 different outcomes reportedly linked to 25-hydroxyvitamin D in the literature, only 10 had also been tested in trials, and only one (birth weight) had evidence to suggest benefit from observational studies and trials.
Chowdhury et al provide a new meta-analysis of observational and trial data relating vitamin D (given alone as either the D2 or D3 preparation), to risk of all cause mortality. Their observational analyses confirmed that low 25-hydroxyvitamin D was associated with elevated risk of multiple adverse outcomes. However, their analysis of RCTs found that whereas D2 supplementation did not seem to reduce all cause mortality (relative risk 1.04, 95% CI 0.97 to 1.11), D3 supplementation did (0.89, 0.80 to 0.99). However, this latter analysis was based on 14 trials (n=13, 637) of which six scored a high risk of bias. The four studies (n=10 197) that contributed the most power to the D3 trial meta-analyses were conducted in older people and had fractures as the primary outcome.
In an accompanying commentary, the authors put these data into context and suggest the following take home messages:
“Firstly, healthcare professionals should treat all observational data cautiously, as existing disease and associated risk factors may cause, rather than be a consequence of, low circulating 25-hydroxyvitamin D.”
“Secondly, before widespread supplementation can be considered, new trial data are needed with a focus on potential risks as well as benefits; further reanalysis of existing data will not suffice. Fortunately, new trials are under way—for example, VITAL, which has recruited 26 000 men and women and randomised them to 2000 IU D3, omega-3 fatty acid, or placebo in a two by two factorial design. Its primary outcomes will be cancer, coronary heart disease, and stroke, and it is due to report around 2017. VITAL will also be able to assess whether any benefits of D3 vary by baseline 25-hydroxyvitamin D concentrations. This study alone will therefore substantially increase the available D3 trial evidence base, and, importantly, extend it to younger people.”
“Finally, while we wait for results of major trials, clinicians should avoid costly measurement of 25-hydroxyvitamin D in asymptomatic patients outside of bone disease related conditions. Some may argue that supplementing those who are apparently “deficient” is cheap, but patients may gain false reassurance from prescription of a “protective” tablet. To improve health and prevent chronic disease, we should stick to what is proven: encourage better lifestyles in general and target established risk factors in people at elevated risk.”