February 18, 2010 — Weekly treatment with 8400 IU of vitamin D₃ raises serum 25-hydroxyvitamin D [25(OH)D] concentrations in elderly, vitamin D–insufficient individuals, according to the results of a randomized controlled, double-blind trial reported online February 3 in the American Journal of Clinical Nutrition.

"Vitamin D insufficiency, which is prevalent in older individuals, is associated with bone and muscle weakness and falls," write Paul Lips, from Vrije Universiteit Medisch Centrum, Amsterdam, Netherlands, and colleagues. "We examined the effects of a weekly dose of 8400 IU vitamin D₃ on postural stability, muscle strength, and safety."

Participants 70 years or older with 25(OH)D concentrations of 20 ng/mL or less but at least 6 ng/mL were randomly assigned to receive a weekly dose of 8400 IU of vitamin D₃ or placebo. The main endpoint of the study was mediolateral body sway with eyes open, measured with use of the AccuSwayPLUS platform (Advanced Medical Technology Inc, Watertown, Massachusetts). The short physical performance battery and serum 25(OH)D concentrations were secondary outcomes. Safety and tolerability were evaluated, and treatments were compared by use of an analysis of covariance model.

Strength of Randomized Study Design

"An increasing number of studies report on significant associations between low serum levels of 25-hydroxyvitamin D (25-(OH)D) and a multitude of extra-skeletal diseases and pathological conditions," Meinrad Peterlik, PhD, MD, professor emeritus of pathophysiology at Medical University Vienna in Vienna, Austria, told Medscape Nutrition when asked for independent comment.

"However, these mostly observational studies are rarely controlled for potential confounders, and interventional trials that would prove a causative relation between a compromised vitamin D status and disease incidence are rare. The main strength of the study by Lips et al. thus lies in the fact that it was designed as a randomized controlled multicenter trial to evaluate the effect of vitamin D₃ supplementation on a well defined neuromuscular functional parameter, i.e., body sway, in a group of elderly people with sub-optimal vitamin D supply."

In patients treated with 8400 IU of vitamin D₃ (n = 114) but not in patients receiving placebo (n = 112), serum 25(OH)D concentrations increased significantly from 13.9 to 26.2 ng/mL (P < .001). Mediolateral sway and short physical performance battery at 16 weeks were not significantly different between treatment groups.

Treatment with 8400 IU of vitamin D₃ was associated with significantly decreased sway vs treatment with placebo (P = .047) in patients with elevated baseline sway but not in patients with normal baseline sway, based on a post hoc analysis of patients subgrouped by baseline sway (≥ 0.46 vs <>

"Weekly treatment with 8400 IU vitamin D₃ raised 25(OH)D concentrations in elderly, vitamin D–insufficient individuals," the study authors write. "Treatment with 8400 IU vitamin D₃ did not reduce mediolateral sway significantly compared with treatment with placebo in this population, although in post hoc analysis, treatment with 8400 IU vitamin D₃ reduced sway in the subgroup of patients who had elevated sway at baseline. Weekly treatment with 8400 IU vitamin D₃ was well tolerated."

Parathyroid hormone levels decreased significantly in the vitamin D₃ group but not in the placebo group. Both groups had similar adverse events and incidences of hypercalcemia, hypercalciuria, and elevated creatinine levels.

Limitations of the Study

"Although the results are straightforward, their interpretation is hampered by a number of facts, most of which are appropriately addressed by the authors themselves," Dr. Peterlik told Medscape Nutrition. "However, they fail to discuss what impact the optimization of calcium intake in the entire study group could have had on the outcome of the study. It could well be that at high calcium intake levels vitamin D supplementation is only minimally effective. This would not be surprising since a recent study by one of the coauthors (Pfeifer et al., Osteoporosis Int. 20:315-322, 2009) shows a positive effect of combined vitamin D and calcium supplementation on parameters of muscle function in elderly people."

Limitations acknowledged by the study authors include small size and unusually healthy condition of the elderly participants. In addition, a substantial number of participants had mediolateral sway values at baseline that were consistent with participants who did not fall, suggesting that their balance as measured by sway was adequate. There may have been little room for improvement of sway and physical performance with treatment in these patients.

"It is clear that elderly individuals with an increased body sway will benefit from a daily dose of 1200 IU vitamin D₃ in combination with intake of > 1000 mg calcium per day," Dr. Peterlik concluded. "Additional studies with fracture rates as endpoint are necessary to prove that the observed reduction of body sway actually has a substantial impact on the incidence of falls and osteoporotic fractures in elderly people."

Merck & Co Inc supported this study, employs 5 of the study authors, and provided research grants to 4 other study authors. Dr. Peterlik has disclosed no relevant financial relationships.

Am J Clin Nutr. Published online February 3, 2010.