Tufts University researcher Beth Dawson-Hughes and her team discovered through a large-scale clinical trial that vitamin D supplements can reduce diabetes risk, but only in individuals with specific genetic variations. This indicates the need for a more personalized approach to diabetes prevention.

Dawson-Hughes and colleagues found that adults with prediabetes carrying a unique mutation in the vitamin D receptor gene had a 19% lower risk of developing diabetes when taking high doses of vitamin D daily.

Dr. Dawson-Hughes and her co-authors analyzed data from the D2d study, a multicenter, randomized, double-blind, placebo-controlled clinical trial conducted from October 1, 2013, to November 28, 2018.

The initial trial investigated the effects of 4,000 units of vitamin D per day versus a placebo on more than 2,000 U.S. adults diagnosed with prediabetes, aiming to assess whether high daily doses of vitamin D could reduce diabetes onset in this high-risk group.

However, no significant decrease in diabetes risk was identified across all participants.

“The D2d results prompt an essential question: Can vitamin D still offer benefits for certain individuals?” explained Dr. Dawson-Hughes.

“Diabetes presents numerous severe complications that develop gradually over many years.”

“If we can delay the duration that an individual lives with diabetes, we can mitigate some of its detrimental effects or lessen their severity.”

Previous analyses by the D2d research team indicated that blood levels of 25-hydroxyvitamin D at 40-50 ng/mL or higher were linked to a significant and steady decrease in the risk of developing diabetes among participants.

Circulating vitamin D is converted into its active form in the body before it interacts with vitamin D receptors, proteins that facilitate cellular responses to the vitamin.

Researchers speculated that genetic variations in the vitamin D receptor could explain why some individuals respond positively to vitamin D supplementation while others do not.

Insulin-producing cells within the pancreas possess vitamin D receptors, leading to hypotheses that vitamin D may influence insulin secretion and blood glucose regulation.

For this latest study, scientists examined genetic data from 2,098 trial participants who consented to DNA testing, categorizing them into two groups: those likely to benefit from vitamin D supplementation and those unlikely to see benefits.

They compared response rates among subgroups based on three common mutations in the vitamin D receptor gene.

The analysis indicated that adults with the AA mutation in the ApaI vitamin D receptor gene (about 30% of the study cohort) showed no response to high daily doses of vitamin D compared to those given a placebo.

Conversely, adults with AC or CC mutations in the vitamin D receptor gene who received the same treatment exhibited a significantly lower risk of developing diabetes compared to those on a placebo.

Anastasios Pittas, a professor at Tufts University School of Medicine, remarked, “These findings could represent a key advancement in creating personalized strategies to lower the risk of type 2 diabetes in high-risk adults.”

“The appeal of vitamin D as a preventive tool stems from its affordability, widespread availability, and ease of use.”

The authors caution that their study’s results do not imply individuals should initiate high doses of vitamin D independently to prevent diabetes.

Current guidelines recommend 600 IU per day for individuals aged 1-70 and 800 IU per day for those over 70.

Excessive vitamin D intake can be detrimental and is associated with an increased risk of falls and fractures in older adults.

Further research is essential to identify who may benefit from augmented daily doses.

“Our findings indicate that we may eventually pinpoint which prediabetic patients are most likely to benefit from additional vitamin D supplementation,” stated Dr. Dawson-Hughes.

“In principle, this could involve a single, relatively inexpensive genetic test.”

Findings are published in the journal JAMA Network Open.

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Beth Dawson-Hughes et al. 2026. Effect of vitamin D supplementation on vitamin D receptor polymorphisms and diabetes risk in prediabetic adults. JAMA Net Open 9 (4): e267332; doi: 10.1001/jamanetworkopen.2026.7332