How safe and well-tolerated is high-dose daily administration of vitamin D3 supplementation in persons with prediabetes?

This study assessed the safety and effectiveness of oral, high-dose daily vitamin D3 for the prevention of diabetes in adults at high risk for type 2 diabetes (T2D). The authors concluded that oral, high-dose daily vitamin D3 at a dose of 4000 IU was safe and well-tolerated in patients with prediabetes that were overweight or obese.

Vitamin D3 (cholecalciferol) may potentially lower the risk of chronic diseases including diabetes, cardiovascular conditions, and cancer. Recently, this interest has extended to clinical trials in which higher than normal doses of vitamin D3 supplementation are administered.

The average, recommended daily allowance (RDA) of vitamin D3 is around 400-800 international units (IU) per day. Since it is a fat-soluble vitamin, excessive use can potentially lead to vitamin D toxicity that can cause side effects like calcium buildup in the blood.

Despite this concern, safety and tolerance have not been adequately investigated to date. There is a need to investigate whether higher doses of vitamin D3 are safe and well-tolerated in patients.

This study included 2423 participants that were overweight or obese and at high-risk for T2D development (prediabetes). 1211 participants were included in the treatment group. They received once-daily, oral vitamin D3 at 4000 IU. 1212 participants were assigned to the placebo group. All study participants were monitored for side effects associated with vitamin D3 supplementation such as high blood calcium levels, high levels of calcium in the urine, kidney stones, and urinary filtration rate (kidney function). Serious side effects were considered as death, life-threatening events, and hospitalizations. Participants were followed for up to 3 years.

After 3 years of follow-up, a total of 8304 side effects occurred. Less frequent side effects were seen in the vitamin D treatment group compared to placebo. Side effects occurred at low frequency and did not differ significantly between the groups. Serious side effects were not significantly different between both groups.

The study showed that vitamin D3 supplementation at 4000 IU daily was safe and well-tolerated, and did not result in an increased risk of side effects in prediabetic persons that were overweight or obese.

The study did not measure other side effects of interest such as reduced bone mineral density and bone strength.