SAN DIEGO — The ability of vitamin D to reduce the risks of cardiovascular disease and cancer are about to be put to the test in a randomized, controlled study.
January will bring the launch of the vitamin D and omega-3 trial (VITAL), a 20,000-participant study that will examine whether daily dietary supplements of vitamin D (about 2,000 IU) or fish oil (about 1 g of omega-3 fatty acids) reduces the risk of developing cancer, heart disease, and stroke.
Speaking at the annual meeting of the North American Menopause Society, Dr. Edward Giovannucci said that observational studies have validated vitamin D status as predictive of cardiovascular disease and cancer risks. The next step is therapeutic intervention with “various ranges of vitamin D. We need to know the dose-response better. We can learn a lot from intermediate end points such as inflammatory markers, but ultimately we need to look at hard end points such as cardiovascular disease and cancer.”
The best studies to date suggest that serum vitamin D levels of 30 ng/mL or more are optimal for reducing the risk of cardiovascular disease and cancer, said Dr. Giovannucci, professor of nutrition and epidemiology at Harvard School of Public Health, Boston.
“There is no credible evidence of any risk associated with this level of intake,” he said, but “we need to weigh benefits and risks” of vitamin D supplementation. Hypothetical associations between vitamin D deficiency and cardiovascular disease include increased levels of vascular calcification, vascular smooth cell proliferation, parathyroid hormone, tumor necrosis factor–alpha, and interleukin-6.
The research also could influence understanding of the pathophysiology of diseases, Dr. Giovannucci said. Elevated parathyroid hormone levels, for example, may contribute to hypertension and left ventricular hypertrophy.
In the Framingham Offspring Study, for example, a vitamin D level of 30 ng/mL or greater was associated with a 50% reduction in risk for a cardiovascular event (Circulation 2008;117:503-11). “The risk flattened off at vitamin D levels of 20-25 ng/mL,” he said.
In the Health Professionals Follow-up Study, a nested case-control study of myocardial infarction or fatal coronary heart disease, Dr. Giovannucci and his associates followed 454 cases and 900 controls for 10 years (Arch. Intern. Med. 2008;168:1174-80). After the investigators controlled for lifestyle factors, cardiovascular disease factors, lipids, and inflammatory markers, the relative risk for MI in those with serum vitamin D levels of 15 ng/mL or less was twice as high as in those with levels of 30 ng/mL or more.
“We also found a very strong association between cases of sudden death and low levels of vitamin D,” Dr. Giovannucci said.
A much larger cohort analysis, the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, found strong associations between vitamin D status and all-cause and cardiovascular mortality (J. Endocrinol. Metab. 2008;93:3927-35). For example, about 35% of patients with vitamin D levels less than 15 ng/mL and 10% of those with levels greater than 30 ng/mL had died after nearly 8 years, he said.
As for vitamin D's effect on cancer risk, the evidence is strongest in colorectal cancer, he said. In breast cancer there have been some negative studies, but the Nurses' Health Study showed a link with borderline significance between vitamin D status andthreast cancer risk in women aged 60 and older (Cancer Epidemiol. Biomarkers Prev. 2005;14:1991-7).
“There could possibly be an age gradient for vitamin D where the level might be more important for older women,” he commented.
Dr. Giovannucci said that he had no relevant financial disclosures.
'There could possibly be an age gradient for vitamin D where the level might be more important for older women.'
Source DR. GIOVANNUCCI