Vitamin D3 supplementation safe, well tolerated in overweight/obese prediabetics

Taking vitamin D₃ supplementation at 4,000 IU per day does not produce any safety concern and is well tolerated among overweight and obese participants who are at risk for diabetes, reports a study.

“In this population, this dose of vitamin D₃ did not increase risk of adverse events (AEs) or serious AEs (SAEs), including those previously associated with vitamin D such as hypercalcaemia, hypercalciuria, or nephrolithiasis,” the researchers said.

A total of 2,423 overweight/obese individuals with prediabetes were randomly assigned to receive either 4,000 IU of vitamin D₃ (the tolerable upper intake level for adults by the National Academy of Medicine) taken daily or matching placebo. All participants were included in the analysis.

The researchers ascertained incident AEs four times a year at in-person visits and interim remote encounters. AEs were defined as untoward or unfavourable medical occurrences, and SAEs included death, life-threatening events, and hospitalizations.

Incident AEs reached a total of 8,304 during 3 years of follow-up and occurred less frequently in the vitamin D group compared to the placebo group (incidence rate ratio [IRR], 0.94, 95 percent confidence interval [CI], 0.90‒0.98). [Eur J Clin Nutr 2022;76:1117-1124]

Overall, there was a low and comparable frequency of protocol-specified AEs of interest, including nephrolithiasis, hypercalcemia, hypercalciuria, or low estimated glomerular filtration rate, between groups. Additionally, no significant between-group differences were observed in total SAEs (IRR, 0.96, 95 percent CI, 0.81‒1.14).

“This finding of no increased risk of AE or SAE in the vitamin D₃ group is reassuring given that the majority of [study] participants began the trial with concentrations of serum 25(OH)D considered sufficient for healthy adults,” the researchers said. [N Engl J Med 2019;381:520-530]

Other trials with vitamin D supplementation found more AEs that were not examined in the present study. For instance, a study in Canada found that vitamin D₃ for 3 years at 4,000 IU or 10,000 IU per day compared with 400 IU per day, resulted in statistically significant lower radial bone mineral density (BMD) among older adults (ages 55‒70 years). [JAMA 2019;322:736-745]

The current study did not assess BMD. Therefore, the researchers cannot provide evidence about the effect of the 4,000 IU per day on BMD and bone strength in overweight/obese people with prediabetes.

In addition, a study in Switzerland tested vitamin D₃ at 60,000 IU per month, compared with 24,000 IU, and found increased risks of falls with the higher dose. [JAMA Intern Med 2016;176:175-183]

In the present study, the researchers did not investigate the participants regarding falls using a validated questionnaire, but the vitamin D group had fewer AEs and SAEs for injury or musculoskeletal events than the placebo group.

“Future trials are warranted to test the efficacy-safety ratio of higher doses of vitamin D supplementation that aim to achieve higher 25(OH)D levels in specific populations at-risk for specific conditions, such as diabetes, osteoporosis, cancer, etc.,” the researchers said.