ORLANDO – The vitamin that keeps bones strong and protects against colon cancer also can, in large doses, increase the risk of falls and fractures.

Studies of high-dose vitamin D keep turning up the same concerns, Dr. Martin Weinstock said at the annual meeting of the American Academy of Dermatology. The most striking of these findings are the significantly increased risks of falls and fractures associated with vitamin D megadoses, said Dr. Weinstock of Brown University, Providence, R.I. These trials examined very-large intermittent doses of the vitamin given to elderly patients.

For example, a single, annual intramuscular injection of 500,000 IU increased the risk of fracture by 50% over 3 years. And oral doses of 60,000 IU per month, given once a month, increased the chance of both falls and fractures.

That amount of vitamin D, taken all at once, may seem like a therapeutic outlier to clinicians who are used to giving 2,000-4,000 IU/day, as recommended by the 2011 Institute of Medicine report.

Not so fast, said Dr. Weinstock.

“If you do the math, if you’re taking 2,000 IU every day, that’s 60,000 IU per month. That’s a high dose,” he said. However, he noted, daily supplements in that range appear safe. “It seems that this intermittent dosing in these studies might be the problem.”

The IOM report, an exhaustive, 1,000-page article summarizing the extant data on vitamin D – is considered the optimal dosing guide. For healthy patients, it recommends the following as minimum effective and maximum safe doses:

400-1,000 IU/day for infants younger than 6 month.
400-1,500 IU/day for infants aged 6-12 months.
600-2,000 IU/day for children aged 1-3 years.
600-3,000 IU/day for children aged 4-8 years.
600-4,000 IU/day for everyone aged 9 years and older.

But dosing of this fat-soluble vitamin should, in some cases, be individualized. For example, obese patients may have persistently low levels despite supplementation, as fat can sequester the vitamin. Patients with fat-metabolizing disorders may not absorb it well. And patients who have had gastric bypass may face the same issues of malabsorption, but from a mechanical, not a metabolic, standpoint.

Elderly people are particularly susceptible to vitamin D deficiency for a couple of reasons, Dr. Weinstock said. They may be less mobile, so lack exposure to sunlight. Age also can decrease the ability to convert 25-hydroxyvitamin D to the biologically active vitamin.

Mega-dosing has been an attractive method of raising and maintaining levels in this population. But several studies illustrate the risks that come along with this strategy, he noted.

A 2007 study randomized 9,440 men and women 75 years or older to placebo or to a single, 300,000 IU vitamin D intramuscular injection for 3 years. At the end of that time, the rate of falls had not significantly changed, but the rate of hip fractures had increased by 49% (Rheumatology [Oxford] 2007;46:1852-7).

Fractures occurred in 585 subjects, including 110 hip fractures, 116 wrist fractures, and 37 ankle fractures. This represented a 49% increase in any hip fracture and a 22% increase in wrist fracture over the placebo group.

A similar study, published in 2010, randomized 2,225 elderly women to placebo or a single 500,000 oral dose of vitamin D for 4 years. There were 171 fractures in the active group and 135 in the placebo group – a 26% increased risk (JAMA. 2010;303[18]:1815-22).

The fall rate in the active group was 83.4/100 person-years, compared with 72.7/100 person-years in the placebo group. This represented a significant 26% increased fracture risk and 15% increased fall risk.

Interestingly, most of these incidents occurred within the first 3 months after each dose,” Dr. Weinstock said. Those taking vitamin D were 31% more likely to fall in that time period, but no more likely to fall in the subsequent 9 months after each dose.

In 2016, a third study looked at functional status among 200 elderly men and women in a three-armed randomization: a low-dose control group receiving 24,000 IU of vitamin D; 60,000 IU vitamin D₃; or 24,000 IU of vitamin plus 300 mcg calcifediol.

Functional status didn’t differ between the groups at the end of 1 year. But the incidence of falls did differ, with falls occurring in 67% of the 60,000 IU group, 54% of the 24,000 IU/calcifediol group, and 48% of the 24,000 IU control group (JAMA Intern Med. 2016;176[2]:175-83).

This represented a 47% increased fall risk in the high dose group, compared with the two low-dose groups.

Dr. Weinstein had no financial disclosures relevant to his lecture.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

Large, intermittent vitamin D doses may increase fracture, fall risk in elderly