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Vitamin D3 Supplementation Fails to Significantly Lower Diabetes Risk in Patients with Pre-diabetes

Study confirms gold standards of weight loss, nutrition and exercise for diabetes prevention


By Sangeeta Kahsyap, MD


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Vitamin D3 supplementation has minimal—if any—clinic benefit in terms of diabetes prevention in patients with pre-diabetes, according to a report published this afternoon in the New England Journal of Medicine. Cleveland Clinic was one of the 22 academic medical centers in the United States that collaborated in the study, along with the National Institute of Diabetes and Digestive and Kidney Diseases.

Speculative claims without clinical evidence

There has been speculation that low vitamin D levels may increase diabetes risk among patients with pre-diabetes, and that supplementation with vitamin D3 might reduce that risk. Until recently, there hasn’t been much in the way of clinical evidence to support or refute such claims.

Our study randomized 2423 participants, all of whom met at least two of three the glycemic criteria guidelines, established by the American Diabetes Association (ADA), for pre-diabetes:

  • fasting glucose of 100-125 mg/dL;
  • plasma glucose of 140-199 mg/dL two hours after taking a 75-gram dose of oral glucose; and/or
  • HbA1c of 5.7% to 6.4%.

We randomly assigned patients into two groups, regardless of their baseline serum 25-hydroxyvitamin D level. The treatment group (n = 1211) took one soft-gel cap containing 4000 IU per day of vitamin D3. The remaining group (n = 1212) received a placebo. Participants were asked to limit any supplementation outside the study to 1000 IU vitamin D3 and 600 mg of calcium per day. We closely monitored the adherence of participants to study protocol, with follow-up visits three and six months after randomization, and twice per year afterward. We also had interim contact with participants via phone or email to encourage retention and adherence.

Vitamin D levels increased, but without significant impact on diabetes risk

Baseline serum levels were 27.7 ng/mL in the treatment group and 28.2 ng/mL in the placebo group. Not surprisingly, serum 25-hydroxyvitamin D levels increased dramatically in the treatment group. After taking the supplements for 24 months, treatment group serum levels increased to 53.6 ng/mL compared to only 28.8 ng/mL in the placebo group.

In order to determine the effect of vitamin D3 supplementation on diabetes risk, we were looking at the time to diabetes incidence based on the ADA’s glycemic criteria or participant use of a diabetes-specific medication.

By the conclusion of the study, 616 diabetes events occurred. Diabetes events were split roughly evenly between the treatment group (47.6%) and the placebo group (52.4%).


We found that, in a population at high-risk for developing T2D not selected based on baseline serum 25-hydroxyvitamin D levels, vitamin D3 supplementation at 4000 IU per day did not significantly reduce the incidence of diabetes.

As we completed our research, two studies were published that found similar results. One study found that supplementing to 20,000 IU per week lowered diabetes risk, but not to a level of statistical significance. Another study supplemented with eldecalcitol, also finding that the vitamin D analog non-significantly lowered diabetes risk.

The gold standard for diabetes prevention remains weight loss, diet and exercise.


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