Effects of three-monthly oral 150,000 IU cholecalciferol supplementation on falls, mobility, and muscle strength in older postmenopausal women: A randomized controlled trial

Abstract

Daily vitamin D in addition to calcium supplementation reduces falls and fractures in older women. However, poor adherence to therapy is a common clinical problem. To examine the effects of supervised oral 3-monthly vitamin D therapy on falls, muscle strength, and mobility, we conducted a 9-month randomized, double-blind, placebo-controlled trial in 686 community-dwelling ambulant women aged over 70 years. Participants received either oral cholecalciferol 150,000 IU every 3 months (n ¼ 353) or an identical placebo (n ¼ 333). All participants were advised to increase dietary calcium intake. Falls data were collected 3-monthly. At baseline, 3, 6, and 9 months, muscle strength was measured by a handheld dynamometer and mobility by the Timed Up and Go (TUG) test. Serum 25 hydroxyvitamin D (25OHD) was measured in a subgroup of 40 subjects. Mean age at baseline was 76.7 AE 4.1 years. The average serum 25OHD value at baseline was 65.8 AE 22.7 nmol/L. By 3, 6, and 9 months after supplementation, 25OHD levels of the vitamin D group were approximately 15 nmol/L higher than the placebo group. Calcium intake did not change significantly between baseline (864 AE 412 mg/day) and 9 months (855 AE 357 mg/day). Faller rates in the two groups did not differ: vitamin D group, 102 of 353 (29%); placebo group, 89 of 333 (27%). At 9 months, compared to placebo or baseline, muscle strength, and TUG were not altered by vitamin D. In conclusion, oral cholecalciferol 150,000 IU therapy administered 3-monthly had neither beneficial nor adverse effects on falls or physical function. These data together with previous findings confirm that intermittent large doses of vitamin D are ineffective or have a deleterious effect on falls. Thus despite adherence issues with daily vitamin D replacement, an intermittent, high-dose vitamin D regimen cannot be supported as a strategy to reduce falls and fractures. ß

Effect of vitamin D supplementation alone or with calcium on adiposity measures: a systematic review and meta-analysis of randomized controlled trials

“…All studies used vitamin D3, except one that used vitamin D2 60 , and another used alphacalcidiol. 61 Table 2 28, 42, 43, 45, 61, 62, 63, 64, 53, 58, 65, 51, 23, 26, 66, 67, 68, 54, 59, 55, 60, 50, 44, 69, 70, 56 provides an overview of the number of participants, methodological quality, and the baseline and end of intervention values of weight, BMI, or FM in each included trial. Twenty-five studies reported no significant effect of vitamin D alone or vitamin D plus calcium supplementation on weight, BMI, or FM.…”

“…( Table 3 ) Together, vitamin D alone versus placebo and vitamin D plus calcium versus calcium control showed no significant reduction in BMI, weight, or FM. ( Table 3; Supplemental Figures 1-3 42, 43, 45, 61, 62, 63, 64, 53, 58, 65, 51, 23, 26, 66, 67, 68, 54, 59, 55, 60, 50) An analysis for dose-response effect by vitamin D3 dose of < 1000, 1000 to < 2000, 2000 to < 4000, and greater than 4000 IU/day ( Figures 2a-2c 42, 43, 45, 61, 62, 63, 64, 53, 58, 65, 51, 23, 26, 66, 67, 68, 54, 59, 55, 60, 50,) revealed no significant effect of vitamin D in any of the dose groups on any of the adiposity outcomes ( all p>0.05). The highest daily dose in the studies included in this meta-analysis was vitamin D3, 12,695 IU/day.…”

Excess 25-hydroxyvitamin D3 exacerbates tubulointerstitial injury in mice by modulating macrophage phenotype

“…A 3-month oral 150,000 IU VD regimen has neither beneficial nor adverse effects on falls or physical function. 22 high-dose VD has been found to be deleterious. Both annual intramuscular injection of VD at a dose of 300,000 IU and annual oral VD administration at a dose of 500,000 IU increase the risk of fractures.…”

The effects of intermittent vitamin D3 supplementation on muscle strength and metabolic parameters in postmenopausal women with type 2 diabetes: a randomized controlled study

“…In this respect, longer intervals of administration of vitamin D3 doses may not be functionally effective [Glendenning et al 2012]. …”