Vitamin D supplements may lower risk by 15{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac}

A single capsule of a vitamin D supplement and it's shadow on a flat surfaceShare on Pinterest
Vitamin D may be beneficial for adults with prediabetes. MirageC/Getty Images
  • Systemic review and meta-analysis have found that individuals with prediabetes could lower their risk of developing type 2 diabetes by 15{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac} by supplementing with vitamin D.
  • However, the reduction of risk with vitamin D was not as great as the reduction achieved by making intensive lifestyle modifications, another study showed.
  • Other researchers caution that individuals should weigh the benefits and risks of taking vitamin D supplements with their doctors.

Individuals with prediabetes have blood sugar levels higher than what is considered healthy but not high enough to be diagnosed as type 2 diabetes.

It is a common condition — about 1 in 3 American adults have prediabetes, according to the U.S. Centers for Disease Control and Prevention. The good news is individuals with prediabetes can still prevent or delay the onset of type 2 diabetes.

A new systemic review and meta-analysis have found a higher vitamin D intake by individuals with prediabetes was associated with a 15{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac} reduced risk of developing type 2 diabetes.

A paper about the review was published in the Annals of Internal Medicine.

Other studies, including one from 2013, have reported an association between an individual’s blood 25-hydroxyvitamin D, a standard measure of the body’s vitamin D levels, and risk for developing type 2 diabetes.

However, the researchers behind the review and analysis point out in their paper that no study has established whether vitamin D supplements decrease the risk of developing type 2 diabetes in patients with prediabetes.

Other studies have looked at vitamin D supplements in people with prediabetes, the researchers write, but “the observed differences were not statistically significant, and the reported relative risk reductions (10{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac} to 13{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac}) were smaller than each trial was powered to detect (25{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac} to 36{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac}).”

Dr. Anastassios G. Pittas, chief of endocrinology, diabetes, and metabolism at Tufts Medical Center and a co-author of the paper about the review, led the D2D study published in 2019 that followed participants at high risk for developing type 2 diabetes who took 4,000 IU of vitamin D daily. With that study, supplementation did not result in a statistically lower risk of diabetes than placebo.

“It showed a 12{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac} relative risk reduction, which was not statistically significant. And that’s because the result was smaller than our trial was powered to detect, which was 25{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac},” Dr. Pittas told Medical News Today.

Two other studies, one which studied participants from Norway and another out of Japan, both showed similar reductions in the number of prediabetic individuals who developed type 2 diabetes. In both cases, those results were not found statistically significant because the reductions were smaller than the studies were designed to detect.

Because the previous results were not found to be statistically significant, the researchers decided to conduct a systemic review and meta-analysis.

“This is what meta-analysis do, especially in the individual participant data; they increase the statistical power of the study to show benefit or risk actually, as well. And so that’s why we combined the data to see if we would be able to show that this result, which was again, so similar amongst the three studies, whether it was statistically significant,” Dr. Pittas said.

For the current review, the authors conducted a systemic review of the published literature looking for randomized, placebo-controlled diabetes prevention trials of vitamin D supplements in adults with prediabetes. That resulted in 3,835 citations from databases PubMed and Embase and 270 records from

Of these, 44 articles and all 270 records were screened. Three trials met the eligibility criteria. These were the 2019 study led by Pittas and the studies out of Norway and Japan.

The study out of Norway looked at 511 participants. The study out of Japan had 1,256 participants. The 2019 study led by Dr. Pittas had 2,423 participants.

The participants were not given the same vitamin D supplementation because of the different locations where the studies were conducted. Participants in the Norway and U.S. study received cholecalciferol, while the Japanese participants received eldecalcitol.

Of the combined 4,190 participants, 44{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac} were women, 51{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac} identified as white or European, 33{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac} identified as Asian, and 15{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac} identified as Black. The mean age of participants was 61. The mean Body Mass Index was 31, and the mean serum 25-hydroxyvitamin D level was 63 nanomoles per liter. The studies had a median follow-up of three years.

A consortium that included subject matter experts and the principal investigator from each study found eligible for the meta-analysis was formed.

Researchers obtained deidentified data sets from each study and gave the databases unified coding. The researchers then performed an IPD meta-analysis of the data.

When the authors of this review compiled individual participant data, they found vitamin D reduced the risk of developing diabetes by 12{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac} in an unadjusted intention-to-treat analysis and 15{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac} in an adjusted intention-to-treat analysis.

The rate of participants experiencing prespecified events like kidney stones, hypercalcemia, and hypercalciuria was low. In the combined analysis, there were no statistically significant differences between vitamin D and placebo groups of adverse effects.

“We’re not super surprised because. [t]he [three separate] trials were very, very similar in the population they studied, in the outcome they measured and in the result was about the same,” Dr. Pittas told MNT.

“You just never know when you do a study what the final result will be, but we’re not super surprised [b]ecause we essentially increased the statistical power. So meta-analysis is almost like doing original trials, but all of a sudden adding two-thirds more of the population,” he added.

The authors of the review point out that the reduction of risk of developing diabetes is not as great as other diabetes prevention strategies.

Intensive lifestyle modification resulted in a 58{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac} lower risk, and taking the drug metformin resulted in a 31{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac} lower risk of developing diabetes in a 2002 study.

An editorial published in the same issue of Annals of Internal Medicine warns that the highest level of vitamin D intake “that carries no appreciable risk for adverse health effects, is set by all government agencies at 100 mcg (4,000 IU).”

The editorial pointed to two randomized clinical trials, including this one from 2018, where adult participants taking 250 micrograms (10,000 international units) of vitamin D daily for one to three years reported increased risk for adverse effects.

The authors go on to advise that “Very-high-dose vitamin D therapy might prevent type 2 diabetes in some patients but may also cause harm.”

That, Dr. Pittas told MNT, is a “reasonable point.”

However, he added a caveat: “[T]he one message I’d like to make that may not be conveyed by this editorial is that the benefit-risk ratio depends on the population and the condition you’re targeting.”

If an individual is at average risk for bone disease, Dr. Pittas provided as an example, the guidelines likely apply to you, “and it’s safe to no risk.”

“But if you are at risk for diabetes, then the guidelines are not very useful if you’re trying to prevent diabetes. And so, according to this meta-analysis, based on the trials, vitamin D at higher doses than typically recommended for the general population for supplement [to] decrease can reduce your risk of diabetes. In the meta-analysis, we did not find any risk.”
— Dr. Anastassios G. Pittas

Dr. Elena Zamora, assistant professor of medicine with McGovern Medical School at UTHealth Houston, pointed out that four in ten adults are believed to be vitamin D deficient.

“The literature in the past has not reached a consensus regarding vitamin D and the correlation of chronic disease, so I appreciated that scholarly activity and meta-analysis has been devoted to this topic. And I think that it’s important that we continue this area of research given that there are vitamin D receptors in our muscle, heart and brain and immune system,” she told MNT.

Dr. Zamora cautioned, however, that the majority of dietary supplements are not regulated.

“We’ve heard about contamination with microbes, metals that may be found in supplements. And so, as more and more correlations with vitamin D levels and chronic comorbid conditions. [are reported], I think we also need to parallel the regulation of supplements,” she said.

Dr. Pittas plans to undertake research in the future looking at what dose of vitamin D provides the best reduction of risk of developing type 2 diabetes in adults with prediabetes with few adverse effects.