Vitamin D – a busy little vitamin often caught in the wrong studies

Interest in vitamin D, which was discovered nearly 100 years ago, has resurged in the past decade as researchers have found a range of health conditions in which vitamin D may play a role. A glance at some of the many recent scientific papers on vitamin D suggests the possibility that it may help to prevent or reduce certain health complications. However, readers should note that many of the studies that the media use to underscore the role of vitamin D in human health are problematic. A major source of this problem is the design of the studies.

Many vitamin D studies are cross-sectional or observational in nature. Such studies are good at finding associations between vitamin D and a range of health conditions, but they cannot prove that a deficiency of vitamin D causes disease or that taking very high doses of vitamin D can prevent or treat a specific condition such as cancer, insulin resistance or heart attacks. Cross-sectional and observational studies are prone to inadvertent bias in their interpretation because of many factors for which they cannot be adjusted.

An example of how an observational study can lead one to draw the wrong conclusions is that at least one study suggested that HIV-positive people who had high levels of vitamin D in their blood also had a high CD4+ cell count. Conversely, people in the same study who had low levels of vitamin D had low CD4+ counts. A simplistic reading of this study would suggest that achieving a high concentration of vitamin D in the blood (by taking large doses) would lead to increased CD4+ cell counts. Yet, to date, two prospective clinical trials—one in HIV-positive adults and the other in HIV-positive children—that tested high doses of vitamin D supplementation have not found any subsequent changes in CD4+ cell counts with vitamin D.

Cross-sectional and observational studies are often faster, cheaper and simpler to conduct than large randomized placebo-controlled clinical trials. Cross-sectional and observational studies can serve as a useful starting point for formulating theories that can be tested in clinical trials of a more robust statistical design. However, cross-sectional and observational studies cannot produce definitive results.

A further complication in understanding the applicability of the results of vitamin D studies is that different studies have used different populations, doses and durations of vitamin D supplementation. Also, emerging research suggests that some people may have certain genes that influence a cell’s ability to respond to vitamin D. All of these factors can affect the outcome of a study. Now, nearly a century since its discovery, in some ways vitamin D research is still in its infancy.

In this issue of TreatmentUpdate we have collected and synthesized important recent data on vitamin D, dosing issues and its potential role for a number of health conditions that can affect people with HIV infection.

—Sean R. Hosein


  1. Holick MF. Vitamin D deficiency. New England Journal of Medicine. 2007 Jul 19;357(3):266-81.