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, professor of medicine at Virginia Commonwealth University, Richmond.
Discussing findings from a recent cross-sectional study involving 340 African Americans 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. Endo. Metab. Jan. 8, 2010; Epub ahead of print PMID:20061416).
“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 wrote.
Recently, a large 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 compared to 54 such events in 42 control subjects (Br. Med. J. 2008; 336:262-6).
The numbers needed to treat (NNT) were “particularly disturbing,” said Dr. Buckley. The NNT for 5 years of supplemental calcium to cause one additional MI than 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, consistent with an initial latent period in which silent vascular damage occurs in advance of climbing cardiovascular event rates.
The vitamin D assay has become one of the most-ordered U.S. lab tests, 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 changing policy such that vitamin D tests for screening purposes would not be covered, 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 that's not what's driving the astounding recent growth in serum vitamin D screening and supplementation. The impetus for the upsurge in screening is the hope that it might protect against a broad range of chronic diseases, including cancers, dementia, autoimmune diseases, and cardiovascular disease.
The trouble is, 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.
“The question we have to ask is: What does that low serum vitamin D level mean? Is it the thing that predisposes, or is it somehow a byproduct of illness?” she continued.
There is intriguing evidence to indicate the optimal level of vitamin D to promote bone health, muscle strength, immunity, and other key functions may vary by race. Data from the National Health and Nutrition Examination Survey show that very few white children ages 1–12 years are vitamin D–deficient using the classic threshold of 15 ng/mL. In contrast, about 10% of non-Hispanic black 1- to 6-year-olds are vitamin D–deficient, as are close to 30% in the 7–12 age bracket (Pediatrics Sept. 2009; e362-70; doi:10-1542/peds.2009-0051).
Many observers see this racial disparity as a public health problem reflecting unequal access to services. But there is a conundrum here: If vitamin D deficiency is rampant in black children, why do they have greater bone strength and muscle mass than whites?
“It makes one wonder whether the definition of normal levels should vary by race,” according to the rheumatologist.
Support for this notion comes from studies showing that pushing serum vitamin D levels to 30 ng/mL or higher in whites reduces their parathyroid hormone levels, while pushing levels above 20 ng/mL in African Americans—young or old—does not further decrease parathyroid hormone or increase bone density.