No evidence of vitamin D health benefits
There is no convincing evidence that vitamin D helps with many of the diseases previously thought to benefit from vitamin D supplements.
Many small studies have found tentative links between vitamin D levels and a long list of diseases such as heart problems, cancers and infections. Evropi Theodoratou and colleagues reviewed these and larger studies and found little evidence to support the conclusion vitamin D helps people with these diseases.
The researchers suggest previous studies that have found links between low vitamin D and a disease might be a result of the disease itself, rather than vitamin D causing the disease.
- Evropi Theodoratou, research fellow1,
- Ioanna Tzoulaki, lecturer23,
- Lina Zgaga, associate professor4,
- John P A Ioannidis, professor56
Accepted 24 February 2014
Objective To evaluate the breadth, validity, and presence of biases of the associations of vitamin D with diverse outcomes.
Design Umbrella review of the evidence across systematic reviews and meta-analyses of observational studies of plasma 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D concentrations and randomised controlled trials of vitamin D supplementation.
Data sources Medline, Embase, and screening of citations and references.
Eligibility criteria Three types of studies were eligible for the umbrella review: systematic reviews and meta-analyses that examined observational associations between circulating vitamin D concentrations and any clinical outcome; and meta-analyses of randomised controlled trials assessing supplementation with vitamin D or active compounds (both established and newer compounds of vitamin D).
Results 107 systematic literature reviews and 74 meta-analyses of observational studies of plasma vitamin D concentrations and 87 meta-analyses of randomised controlled trials of vitamin D supplementation were identified. The relation between vitamin D and 137 outcomes has been explored, covering a wide range of skeletal, malignant, cardiovascular, autoimmune, infectious, metabolic, and other diseases. Ten outcomes were examined by both meta-analyses of observational studies and meta-analyses of randomised controlled trials, but the direction of the effect and level of statistical significance was concordant only for birth weight (maternal vitamin D status or supplementation). On the basis of the available evidence, an association between vitamin D concentrations and birth weight, dental caries in children, maternal vitamin D concentrations at term, and parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis is probable, but further studies and better designed trials are needed to draw firmer conclusions. In contrast to previous reports, evidence does not support the argument that vitamin D only supplementation increases bone mineral density or reduces the risk of fractures or falls in older people.
Conclusions Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable.
The associations between vitamin D concentrations and various conditions and diseases have been assessed in a large and rapidly expanding literature. In addition to observational studies, numerous randomised trials have examined the effect of vitamin D supplementation on a range of outcomes. Historically, vitamin D had been linked to skeletal disease including calcium, phosphorus, and bone metabolism,1 2 osteoporosis,3 fractures,4 5 muscle strength,6 and falls.7 In the 2000s, growing scientific attention turned to non-skeletal chronic diseases as vitamin D deficiency was linked to cancer,8 cardiovascular diseases,9 10 metabolic disorders,11 infectious diseases,12 and autoimmune diseases,13 14 15 as well as mortality.16 If causal, these associations might be of great importance for public health, as vitamin D deficiency has been found to be highly prevalent in populations residing at high latitudes or leading an indoors oriented lifestyle.17 However, the composite literature is often confusing and has led to heated debates about the optimal concentrations of vitamin D and related guidelines for supplementation.18 19 20
To provide an overview of the breadth and validity of the claimed associations of vitamin D with diverse outcomes, we have done an umbrella review of the evidence across existing systematic reviews and meta-analyses. We aimed to do a comprehensive evaluation of systematic reviews and meta-analyses of observational studies that examined associations of vitamin D concentrations with a range of clinical outcomes, as well as meta-analyses of randomised controlled trials of vitamin D supplementation. We also compared the findings of the observational studies with those from meta-analyses of randomised controlled trials of vitamin D supplementation, whenever these could be juxtaposed. We sought to summarise the health outcomes that have been associated with vitamin D concentrations, evaluate whether evidence exists of biases in this literature, identify health outcomes without evidence of biases, and examine the consistency of inferences from the meta-analyses of observational studies and of randomised controlled trials.