Publications from clinical trials of vitamin D supplementation have increased substantially over the last 15 years. Yet, despite the growing number of randomized controlled trials, meta-analyses of these studies have drawn inconsistent conclusions. Many meta-analyses assume that vitamin D is a pharmacological agent, and give scant consideration of it being a nutrient. This limits their potential to detect beneficial effects in participants with vitamin D deficiency. An increasing body of evidence from both observational studies and clinical trials supports the presence of thresholds in vitamin D status below which disease risk increases and vitamin supplementation has beneficial effects. Future supplementation trials which seek to replicate these findings should recruit sufficient numbers of participants with low vitamin D levels, and not give low-dose vitamin D to the placebo group. If the presence of vitamin D thresholds for beneficial effects is confirmed, this would strengthen the need for vitamin D fortification of foods.
Keywords: dose–response; randomized controlled trials; thresholds; vitamin D supplementation.