A recent randomized controlled trial (RCT) published in Journal of the American Medical Association made headlines throughout the world, with experts being quoted as advising older women to only take 600 to 800 IU/day.
Let’s look at the study in depth: 230 postmenopausal women with baseline 25(OH)D levels between 14 and 27 ng/ml were randomized into one of three groups: placebo, 800 IU/day or 50,000 IU every two weeks. The women received the assigned treatment for one year. The primary end point was total fractional calcium absorption (TFCA) from the intestine. Bone mineral density was a secondary end point as were muscle function, muscle mass, trabecular bone score, bone turnover, pain, functional status, and physical activity.
Contrary to the news stories, that primary endpoint was positive; that is, the women on high dose vitamin D (50,000 IU every two weeks) had better calcium absorption. The study showed TFCA increased 1% in the high-dose arm but decreased 2% in the low-dose arm (P = .005 vs high-dose arm) and decreased 1.3% in the placebo arm (P = .03 vs high-dose arm).
Although this difference is not large, osteoporosis takes decades to develop. Would you rather have improved calcium absorption or worsened calcium absorption for the rest of your life? Remember, this study took place for only one year, not one decade.
However, the only secondary end point that was positive in the high dose group was femoral neck bone mineral density, and that disappeared with adjustment. These findings were indeed disappointing.
It’s important to take a closer look at the study design. The low dose group took 800 IU/day, but the high dose group took 50,000 IU every two weeks. Why? Large doses every two weeks are physiologically different than higher daily dosing. Since the researchers had one group taking vitamin D daily, the other groups should have also received a daily pill. This may explain why the secondary endpoints were not met.
My next observation is that the researchers did not conduct a subgroup analysis. Did the women who had lower baseline 25(OH)D levels respond any differently than the women who had higher baseline levels? The authors could have easily done such an analysis, but did not publish it if they did.
Finally, no one I know says vitamin D alone will prevent or treat osteoporosis. It is a complex disease with many nutrients (and drugs) involved in both its prevention and treatment. For example, a RCT found vitamin K helped bone indices.
Koitaya N, Sekiguchi M, Tousen Y, Nishide Y, Morita A, Yamauchi J, Gando Y, Miyachi M, Aoki M, Komatsu M, Watanabe F, Morishita K, Ishimi Y. Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women. J Bone Miner Metab. 2014 Mar;32(2):142-50.
Likewise, a RCT of magnesium showed it helped bone health.
Carpenter TO, DeLucia MC, Zhang JH, Bejnerowicz G, Tartamella L, Dziura J, Petersen KF, Befroy D, Cohen D. A randomized controlled study of effects of dietary magnesium oxide supplementation on bone mineral content in healthy girls. J Clin Endocrinol Metab. 2006 Dec;91(12):4866-72.