Early Research Points to Link Between Vitamin D and Heart Health
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Early Research Points to Link Between Vitamin D and Heart Health | Vitamin D, cardiovascular health, VITAL trial

First Clinical Trial Set to Begin

Physicians regularly tell their patients that a healthy diet and habitual exercise are keys to cardiovascular health, but a decade from now will proper vitamin D levels be added to the list? A growing body of observational data builds a strong case, but researchers agree that clinical trials are the necessary next step.

“The big money question is that we’ve identified insufficient vitamin D to be a risk factor, but if someone is deficient and we treat them with vitamin D, can we actually prevent heart attacks? That’s the part we don’t know. That takes a clinical trial,” explained Erin D. Michos, MD, MHS, an assistant professor in the Division of Cardiology at Johns Hopkins University.

Last November, Michos and several other researchers presented vitamin D-related studies at the American Heart Association’s Scientific Sessions 2010 in Chicago. The data revealed hopeful links between sufficient vitamin D levels and heart and vascular health. In fact, Michos’ research offers epidemiological evidence that ties low vitamin D levels to high blood pressure, diabetes and obesity, which are all cardiovascular risk factors. “I looked at several populations, looking at the relation of vitamin D with both markers of vascular disease and also the risk of mortality,” she said.

In 2008, Michos co-authored a study with Michal L. Melamed, MD, at Albert Einstein College of Medicine in New York, that correlated the vitamin D levels of 13,000 kidney patients with the National Death Index eight to nine years later. “What we found is that adults who had the lowest levels of vitamin D had a 26 percent increased risk of all-cause mortality,” Michos said. “This was independent of numerous risk factors.”

Vitamin D has long been known to strengthen bone, yet Melamed noted that researchers are linking lack of vitamin D to a host of other maladies. “There’s all this very intriguing data that has not quite been proven yet that low vitamin D levels have been associated with high blood pressure, diabetes, different sorts of cancers and all-cause mortality, and even newer, less rigorous evidence has linked low vitamin D levels to autism and cognitive dysfunctions,” she said. Michos said other researchers have linked low vitamin D levels with increased risk of myocardial infarction and peripheral artery disease in the legs. At the November sessions, she also presented research tying low vitamin D levels to an increased risk of fatal stroke.


Just a fad?

In the medical community, there are vitamin D enthusiasts and then there are skeptics who believe the hoopla surrounding vitamin D is uncalled for. They point to beta carotene, folate and vitamins C and E as examples of supplementation fads that leveled off once clinical trials revealed no measureable health benefits. Yet Alice H. Lichtenstein, DSc, a professor of nutrition science at Tufts University, said the vitamin D debate is different. “The focus is more on nutrient insufficiency as opposed to the nutrient at supplemental levels,” she said, adding, “Although the observational data are interesting, they can be confounded.”

Sylvia Christakos, PhD, is a noted vitamin D researcher at the New Jersey School of Medicine in Newark. Her work has linked vitamin D with inhibiting the growth of breast-cancer cells, with reversing multiple sclerosis effects in mouse models, and with strengthening the immune system. She said vitamin D in its active form (after its trip through the liver and kidneys) “acts like a steroid hormone.” That’s what puts research into vitamin D in a different category than studies of other vitamins. Much of Christakos’ research focuses on mechanisms at the gene level.


Cardiology findings

Put J. Brent Muhlestein, MD, in the category of vitamin D enthusiast. Director of cardiovascular research at Intermountain Medical Center in Utah, he said, “Vitamin D receptors are actually present on all sorts of different tissues in the body, not just in the bone world and in the parathyroid gland.” One small paper piqued his interest in vitamin D’s effect on heart health – research examining offspring from the famed Framingham study. “After adjusting for every other variable they could find, there was a doubling of the risk in general of cardiovascular complications in patients who had low vitamin D,” Muhlestein explained.

That’s when he decided to mine the wealth of data collected by Intermountain’s catheterization laboratory. Muhlestein and his team looked at 1,497 subjects with at least one vitamin D blood measurement from 2000-2009. What they found is that 16.6 percent of that population suffered what he described as “severe vitamin D insufficiency,” a level of 15 nanograms per milliliter or below. There was very little difference when the data were stratified by age or gender. “The prevalence of cardiovascular problems was higher in the patients who had very low vitamin D levels,” he said. In fact, those who were extremely deficient were almost twice as likely to have died or suffered a stroke than those with adequate amounts.

Muhlestein now regularly checks the vitamin D levels of his patients, and he’s finding consistently low levels in his clinic population.

Muhlestein said he was “a little disappointed” with vitamin D and calcium guidelines released on Nov. 30 by the Institute of Medicine. The report said a level of 20 is sufficient for good bone health and estimated the average daily requirement of vitamin D at 400 international units. Muhlestein believes a level of 30 should be an absolute minimum level and, in fact, he maintains his own vitamin D level at 40.

Ravi Thadhani, MD, MPH, an associate professor at Massachusetts General Hospital, presented research at the November AHA meeting. His animal studies have shown that the active form of vitamin D can prevent the progression of cardiac hypertrophy and even induce its regression. Thadhani gives his kidney patients the hormone form of vitamin D for bone health, and now he’s asking the question: does it have an effect on their heart? He’s performing multi-center, randomized trials looking at whether patients with kidney disease who are treated with an active hormone form of vitamin D over time have improved heart structure as well as function. Those studies involve sophisticated imaging techniques like MRI and cardiac echo, and results should be available by mid-year.

The first randomized, controlled clinical trial to determine whether vitamin D supplementation benefits patients with risk of cardiovascular disease is set to begin soon. Called the VITAL (VITamin d and omegA-3 triaL) trial and funded by the National Institutes of Health, it should produce results in six to eight years.

Meanwhile, should people take a vitamin D supplement? Muhlestein takes 5,000 international units a day, Michos takes 1,000 a day and Christakos takes 3,000.



cardiovascular health, VITAL trial, Vitamin D

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