Perils of High-dose Vitamin D Supplementation
By William C. Haas III, MD, MBA
Integrative Medicine Fellow, Department of Family and Community Medicine, University of Arizona, Tucson
Dr. Haas reports no financial relationships relevant to this field of study.
SOURCE: Bischoff-Ferrari H, et al. Monthly high-dose vitamin D treatment for the prevention of functional decline. JAMA Intern Med 2016; doi:10.1001.
- High-dose vitamin D supplementation (~2000 IU daily) increased the risk of falls in elderly patients > 70 years of age without improving physical functioning.
The Endocrine Society recommends that adults ≥ 70 years of age should supplement with 800 IU of vitamin D daily.1 Unfortunately, raising blood levels of 25-hydroxy vitamin D above the level of insufficiency (> 30 ng/mL) often requires at least 1500-2000 IU daily.2 Recent trials also indicate that supplementing with 800 IU daily neither improves physical function nor reduces the risk of injurious falls.3,4
In an attempt to determine whether high-dose vitamin D would lower the risk of functional decline and/or falls, Bischoff-Ferrari et al conducted a 12-month clinical trial involving different levels of vitamin D supplementation. Two-hundred patients > 70 years of age were randomized into three different groups: Group 1 received 24,000 IU of vitamin D3 once per month (equivalent to 800 IU/day), group 2 received 60,000 IU of vitamin D3 once per month (equivalent to 2000 IU/day), and group 3 received 24,000 IU of vitamin D3 + 300 mcg of calcifediol (liver metabolite of vitamin D). The latter two groups represented the high-dose treatment groups. The primary outcome was improvement of lower extremity function, while the secondary outcome was the number of monthly falls. Lower extremity function was assessed using the Short Physical Performance Battery (SPPB), consisting of timed walking speed, successive chair stands, and a balance test.
When compared to the low-dose group, the two high-dose groups did not experience improvements in lower extremity physical performance. In fact, physical performance failed to improve despite the fact that 80% of the high-dose participants achieved 25-hydroxy vitamin D levels of ≥ 30 ng/mL. Of note, approximately 50% of the low-dose group achieved 25-hydroxy vitamin D levels of ≥ 30 ng/mL and also failed to improve physical performance. With regard to secondary outcomes, the high-dose groups experienced a significantly increased overall risk of falls (P = 0.048) compared to the low-dose group (60,000 IU = 66.9%; 95% confidence interval [CI], 54.4%-77.5%; 24,000 IU + 300 mcg calcifediol = 66.1%; 95% CI, 53.5%-76.8%; 24,000 IU = 47.9%; 95% CI, 35.8-60.3). In terms of actual falls during the 12-month follow-up period, the 60,000 IU group experienced an average of 1.47 falls compared to an average of 1.24 and 0.94 for the 24,000 IU + 300 mcg calcifediol and 24,000 IU groups, respectively (P = 0.09).
The present study confirms that much remains to be learned regarding vitamin D supplementation. Additional studies are required to make definitive claims regarding vitamin D supplementation and physical performance/fall risk. Suggestions for follow-up studies include supplementing with the same protocol on a daily basis mirroring typical consumption patterns as well as supplementing at a slighter higher dose (5000 IU/day) mirroring common prescribing patterns.
- Holick M, et al. Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society Clinical Practice guideline. J Clin Endocrinol Metab 2011;96:1911-1930.
- Holick M. Vitamin D deficiency. N Engl J Med 2007;357:266-281.
- Uusi-Rasi K, et al. Exercise and vitamin D in fall prevention among older women: A randomized clinical trial. JAMA Intern Med 2015;175:703-711.
- Hansen KE, et al. Treatment of vitamin D insufficiency in postmenopausal women: A randomized clinical trial. JAMA Intern Med 2015;175:1612-1621.
Bischoff-Ferrari H, et al. Monthly high-dose vitamin D treatment for the prevention of functional decline. JAMA Intern Med 2016; doi:10.1001.
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