SNOWMASS, COLO. — Serious questions exist about the safety and efficacy of the popular practice of high-dose vitamin D supplementation across a broad swath of the population.
One of these concerns is that not all of the extra calcium absorption promoted by boosting vitamin D is going into bone to prevent fractures. Some of it may actually be taken up by atherosclerotic plaque, increasing the risk of cardiovascular events, Dr. Lenore M. Buckley cautioned at a symposium sponsored by the American College of Rheumatology.
This is of particular concern in patients with known coronary disease and for those at high risk, including individuals with rheumatoid arthritis, systemic lupus erythematosus, diabetes, or psoriasis, added Dr. Buckley, a professor of internal medicine at Virginia Commonwealth University, Richmond.
Discussing findings from a recent cross-sectional study involving 340 African American patients with type 2 diabetes, Dr. Buckley said that serum 25-hydroxyvitamin D levels were positively associated with increased calcified atherosclerotic plaque in the aorta and carotid arteries (J. Clin. Endocrinol. Metab. 2010 Jan. 8 [doi:10.1210/jc.2009-1797
“The effects of supplementing vitamin D to raise the serum 25-hydroxyvitamin D level on atherosclerosis in African Americans are unknown. Prospective trials are needed,” the investigators said.
A recent prospective randomized trial assessed the effects of using calcium supplements on vascular event rates, but it did not involve African Americans. The trial involved 1,471 healthy postmenopausal New Zealand women who were randomized to receive either supplemental calcium or placebo. By 5 years of follow-up, there were a total of 101 myocardial infarctions, strokes, and sudden deaths in 69 women in the supplemental calcium group, and 54 such events in 42 controls (BMJ 2008;336:262-6).
The numbers needed to treat (NNT) were “particularly disturbing,” in Dr. Buckley's view. The NNT required for 5 years of supplemental calcium to cause one additional MI, compared with placebo, was 44. The NNT for one stroke was 56. And the NNT to cause one additional cardiovascular event was 29. In contrast, the NNT to prevent one symptomatic fracture was 50.
The vascular event rate was higher in women with high compliance with calcium supplementation. The event rate was also higher during months 30-60 of follow-up, which is consistent with an initial latent period during which undetected vascular damage may occur.
There is a noticeable, if anecdotal, increase in the number of physicians ordering serum vitamin D tests to screen for deficiency. The vitamin D assay has become one of the most-ordered lab tests in the United States, despite the assay's questionable reliability, its $40-$200 cost, and considerable unresolved debate as to what constitutes an optimal blood level. Medicare is considering denying coverage of vitamin D tests for screening purposes, according to Dr. Buckley.
There is solid evidence that vitamin D supplementation reduces fracture risk in the elderly, especially in those with low serum levels. But the impetus for the upsurge in serum vitamin D screening and supplementation is the hope that it might protect against many chronic diseases, including cancers, dementia, autoimmune diseases, and cardiovascular disease.
However, that hope is driven mostly by epidemiologic data, which must be viewed as hypothesis-generating rather than definitive. The classic example of how misleading epidemiologic associations can be is the expectation that estrogen replacement would reduce cardiovascular risk in postmenopausal women; when the Women's Health Initiative and other prospective trials were eventually carried out, it turned out just the opposite was true, Dr. Buckley noted.
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