From JAMA Internal Medicine, “Treatment of Vitamin D Insufficiency in Postmenopausal Women: A Randomized Clinical Trial“:
Importance Experts debate optimal 25-hydroxyvitamin D (25[OH]D) levels for musculoskeletal health.
Objective To compare the effects of placebo, low-dose cholecalciferol, and high-dose cholecalciferol on 1-year changes in total fractional calcium absorption, bone mineral density, Timed Up and Go and five sit-to-stand tests, and muscle mass in postmenopausal women with vitamin D insufficiency.
Design, Setting, and Participants This randomized, double-blind, placebo-controlled clinical trial was conducted at a single center in Madison, Wisconsin, from May 1, 2010, through July 31, 2013, and the final visit was completed on August 8, 2014. A total of 230 postmenopausal women 75 years or younger with baseline 25(OH)D levels of 14 through 27 ng/mL and no osteoporosis were studied.
Interventions Three arms included daily white and twice monthly yellow placebo (n=76), daily 800 IU vitamin D3 and twice monthly yellow placebo (n=75), and daily white placebo and twice monthly 50,000 IU vitamin D3 (n=79). The high-dose vitamin D regimen achieved and maintained 25(OH)D levels ≥30 ng/mL.
Main Outcomes and Measures Outcome measures were 1-year change in total fractional calcium absorption using 2 stable isotopes, bone mineral density and muscle mass using dual energy x-ray absorptiometry, Timed Up and Go and five sit-to-stand tests, functional status (Health Assessment Questionnaire), and physical activity (Physical Activity Scale for the Elderly), with Benjamini-Hochberg correction of P values to control for the false discovery rate.
What we have here is a randomized controlled trial of Vitamin D supplementation in 230 postmenopausal women 75 years of age or younger who had diagnosed Vitamin D deficiency but no osteoporosis yet. Seems like this is the population where Vitamin D supplementation would work. There were three arms: placebo, low-dose supplementation, and high-dose supplementation. Women were followed for a year.
Ready for the results? In the high dose arm, calcium absorption went up 1%. It went down 1.3% in the placebo arm. It went down more, or 2%, in the low-dose arm. So… I don’t know.
And in other results? There was no impact in spine, mean total-hip, mean femoral neck, or total-body bone mineral density. There was no effect on trabecular bone score. No effect on muscle mass. No effect on functional tests. There were no changes in falls, number of people who fell, physical activity, or functional status.
So… what are we doing? Maybe we’d see results long after one year, but in what? From the Editor’s note:
Of more clinical importance, neither dose of cholecalciferol improved bone density, strength, muscle mass, functional status, or fall rate. It is possible that treatment beyond 1 year would result in better outcomes, but these data provide no support for use of higher-dose cholecalciferol replacement therapy or indeed any dose of cholecalciferol compared with placebo.
If supplementation with a vitamin for an actual deficiency of that vitamin has no impact on bone measurements and actual outcomes, then what’s the point? Maybe deficiency doesn’t mean what we think it does. Giving people the supplements seems to make no sense. I’m baffled.