Vitamin D enthusiasts may be disappointed by the results of a clinical trial reported today at the American Diabetes Association meeting in Philadelphia, Pennsylvania. Huge supplemental doses of vitamin D did to not curb type 2 diabetes in people at high risk of the disease.

Vitamin D — a nutrient derived naturally from exposure to sunlight and, to a lesser extent, from certain foods — is the latest rage in the vitamin world. In the United States, sales of vitamin D supplements rose tenfold between 2001 and 2009.

Some doctors and nutritionists recommend that people take high-dose supplements to avoid diabetes, despite the fact that a panel convened by the US Institute of Medicine (IOM) found the evidence lacking in support of a role for the vitamin in non-skeletal health.

To put an end to the debate, Mayer Davidson, a diabetes researcher at Charles R. Drew University in Los Angeles, California, and lead investigator on the trial, gave people at risk of diabetes a placebo or an enormous dose of vitamin D3. In the past, vitamin D advocates have brushed aside studies with negative results by saying that investigators offered too low a dose. “I wanted to do a once-and-for-all trial,” Davidson says.

An ultimate answer?

Once a week for a year, participants in the treatment arm of the study took an average of 88,865 international units (IU) of vitamin D3, so that their circulating blood levels were 70 nanograms per millilitre. That dose is 21 times what the IOM recommended in their 2010 guidelines and three times what they said was safe. But Davidson says he saw no sign of harm, including kidney stones, which have occurred infrequently in other high-dose trials.

Rather than wait for healthy people to acquire type 2 diabetes, Davidson enrolled only those at high risk of the disease. The participants all were either Latinos or African Americans diagnosed with ‘pre-diabetes’ because their blood glucose levels were higher than normal.

Without drugs or behavioural interventions, roughly 10% of people with ‘pre-diabetes’ become diabetic per year, Davidson says. By the time his year-long trial ended, 9% of the participants in the placebo group had acquired the disease, compared to 12% of those in the treatment group. Statistically speaking, that difference was probably due to chance. “What we saw was that vitamin D did not change the natural history of the disease,” Davidson says, adding, “I think vitamin D’s a dead end for diabetes.”

D remains on trial

However, according to some, the case on D and diabetes will remain open because of deficiencies in Davidson’s trial design. Cliff Rosen, director of clinical and translational research at Maine Medical Center Research Institute in Scarborough, points out that only about 100 people completed the trial, and that it lasted only a year. Larger and longer clinical trials would yield more certain results, Rosen says. He and his colleagues have planned a placebo-controlled trial involving 2,200 subjects with pre-diabetes, half of whom would be given 4000 IU a day for three years. That dose is consistent with the IOM’s warning, says Rosen, who served on the IOM panel.

More studies are needed, because the trend isn’t all hype, Rosen says, in the sense that biology makes the diabetes–vitamin D link plausible. Proteins that interact with the active form of vitamin D, 1,25-dihydroxyvitamin D, pepper the beta cells in the pancreas that mediate diabetes. And people with diabetes tend to have low levels of vitamin D circulating in their blood.

Still, these findings don’t prove causation. It’s not clear whether or how vitamin D influences insulin secretion from beta cells, and the nature of the sunshine vitamin makes association studies near impossible to interpret. For example, a person who exercises outside, takes a multivitamin and eats fish as opposed to red meat will obtain more than enough vitamin D. He or she may also have a lower chance of acquiring diabetes, and that may or may not be due to the nutrient.