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Is High-Dose Vitamin D Harmful in Women?

— Significantly more bone loss at year 3 with 10,000 IU/day for women, but not men

Last Updated September 15, 2020
Ƶ MedicalToday

High-dose vitamin D supplementation may have harmful effects on postmenopausal women, a post-hoc analysis of randomized clinical trial data suggested.

Over a 3-year period, women who received 400 IU of vitamin D daily had a -1.8% loss in total bone mineral density (BMD) at the radius, reported Lauren Burt, PhD, of the University of Calgary in Canada, and colleagues.

In contrast, those given 4,000 IU per day had a -3.8% loss in total BMD at the radius, and those receiving 10,000 IU per day had a -5.5% loss, which was statistically significant (P=0.002), she said during the virtual American Society for Bone and Mineral Research meeting.

Vitamin D is commonly prescribed for the prevention of deficiency-related falls and fractures, but during recent years there has been a change in the perspective surrounding vitamin D supplementation. A systematic review suggested that there is little justification to use vitamin D supplementation to maintain or improve musculoskeletal health.

Moreover, Burt and colleagues recently reported in a that treatment of community-dwelling healthy adults with 4,000 or 10,000 IU of vitamin D per day was associated with significantly lower radial BMD compared with 400 mg.

That study did not analyze the data according to sex, and because sex-related differences in BMD are well documented, the investigators conducted an additional exploratory analysis to consider possible differences in effects between men and women who were not vitamin D deficient.

A total of 303 individuals were included. Their average age was 62, 53% were men, and mean BMI was 28. Total hip BMD scores ranged from -0.5 to 0.7, and mean level of 25(OH)D was 78 nmol/L, which indicated vitamin D sufficiency.

The radius and tibia were scanned on high-resolution peripheral quantitative CT to measure total volumetric BMD at baseline and at 6, 12, 24, and 36 months. In addition, fasting C-telopeptide of type 1 collagen (CTx) and amino-terminal propeptide of type 1 collagen (P1NP) were assessed.

Unlike for women, who had a clear dose response, no significant bone loss or difference according to dose at month 36 at the radius was observed for men, with losses of -0.9%, -1.3%, and -1.9% for 400 mg, 4,000 mg, and 10,000 mg/day, respectively.

Similar results were observed at the tibia, though at a smaller magnitude, with women again having a significant dose response relationship. Among women given 400 mg/day, the change at 3 years was -1%, while among those receiving 4,000 or 10,000 mg/day, changes were -2% and -3.2% (P=0.005). For men, again there was no difference, with changes of -0.1%, 0%, and -0.6%, respectively.

Additional findings included a trend for women in the 10,000 IU group to have higher CTx values than those in the 400-mg group as well as a trend for women to have slightly higher P1NP values.

"Our results support those of the recent trial, finding no detectable effect of vitamin D supplementation and sex effects, although the VITAL trial did report a trend for smaller decreases in areal BMD at the spine in women," she said.

"This post-hoc analysis raises the possibility that vitamin D doses at or above the tolerable intake level may be detrimental in healthy postmenopausal women," Burt concluded, adding that the findings are "clinically relevant" because vitamin D supplementation is widely administered to postmenopausal women for osteoporosis prevention.

Disclosures

Burt disclosed no relevant relationships with industry.

Primary Source

American Society for Bone and Mineral Research

Burt L, et al "High-dose vitamin D supplementation affects bone density differently in females than males" ASBMR 2020; Abstract 1019.