Inadequate levels of vitamin D are associated with an increase in the risk of cardiovascular disease and death, a new observational study has found. Dr Tami L Bair (Intermountain Medical Center, Murray, UT) reported the findings here at the American Heart Association 2009 Scientific Sessions.
Bair and colleagues followed more than 27 000 people 50 years or older with no history of cardiovascular disease for just over a year and found that those with very low levels of vitamin D (<15 ng/mL) were 77% more likely to die, 45% more likely to develop coronary artery disease, and 78% more likely to have a stroke than those with normal levels (>30 ng/mL). Those deficient in vitamin D were also twice as likely to develop heart failure as those with normal levels.
"We concluded that even a moderate deficiency of vitamin D was associated with developing coronary artery disease, heart failure, stroke, and death," said coauthor Dr Heidi May (Intermountain Medical Center). However, "it is not known whether this is a cause and effect relationship," she told heartwire. Because this study was observational, more research is needed "to better establish the association between vitamin D deficiency and cardiovascular disease," she noted.
Evidence so far suggestive of benefit of vitamin D
Vitamin D was the subject of much discussion in a general session on vitamins at the AHA scientific sessions. Although the evidence supporting the benefits of vitamin D in cardiovascular disease is probably stronger than for any other vitamin, there have been only a few randomized clinical trials, and previous observational studies "show no robust effects," said Dr Harald Dobnig (Medical University of Graz, Austria). The latter suffer from limitations, such as doses of vitamin D supplementation that are too low, low compliance rates, and short study duration, he noted.
There are some large randomized trials underway looking at outcomes with vitamin D; it is hoped that they will provide definitive answers in five to seven years, Dr Eric Rimm (Harvard School of Public Health, Boston, MA) explained.
"I think there's promise for vitamin D. We know that most people have insufficient vitamin D levels in their blood," Rimm told heartwire. "So although it will take five years until some of the trials that are adequately powered to look at cardiovascular disease with vitamin D will report, the epidemiology right now is suggestive that people should have 1000 or 2000 IU of vitamin D a day," he said.
Vitamin D: How do we get it, and how much is enough?
Rimm discussed vitamin D at length, explaining that there are two sources: sunlight in the form of UVB rays, and diet (foods and supplementation). "Many tissue types and cells in the body have vitamin D receptors, and the active form of vitamin D is modulated by calcium and parathyroid hormone," he explained, with potential downstream effects on a number of bodily systems—inflammatory markers and the renin angiotensin system to name just two—he said.
People at highest risk of vitamin D deficiency include those with darker skin, those living at high altitudes, the elderly (because there is less of the precursor for vitamin D in the blood as people age and older people tend to spend less time outside), the obese, those who avoid the sun or cover the skin in the sun, those who are the immobilized or institutionalized, and pregnant and breast-feeding women.
Deficiency in vitamin D is generally agreed to be a blood level of <20 ng/mL, he said, with 20-29 ng/mL indicating insufficient vitamin D, 30-60 ng/mL indicating adequate vitamin D, and >150 ng/mL indicating excessive vitamin D.
Data suggest that many people are likely getting inadequate vitamin D, he said, with studies showing that black Americans have blood levels ranging from 6-18 ng/mL and that white Americans have levels ranging from 16-25 ng/mL.
In general, a supplement of 100 IU of vitamin D per day will increase blood levels of vitamin D by 1 ng/mL, Rimm said. Those taking 1000 IU per day should have blood levels in the range of 25-32 ng/mL and those taking 4000 IU should have levels of 40-50 ng/mL.
Diet and sunshine good sources of vitamin D
However, Rimm stressed that vitamin D need not just come from supplements. "I think for vitamin D, it's a shame just to count on supplementation because, during the right times of year, five to 10 minutes a day of sunlight is sufficient is to make enough vitamin D. I do hear the concerns about skin cancer and I think people should wear suntan lotion, but it's probably better to put it on 10 minutes after you've been in the sun."
He cautioned that "in northern climes, even if you go out in the sun in January, you're not going to make much vitamin D, so there you would need supplementation to get adequate levels."
People should remember that diet is an important source of vitamin D, too, he noted. "One of the best dietary sources of vitamin D is fish. We already suggest people eat a couple of servings a week, but having three or four servings a week of fish can get you a fair bit of vitamin D, and would represent an additional 300 to 500 IU of vitamin D. This still might not be sufficient so you might need a little bit of sunlight or to take a vitamin D supplement. It's really a combination of things, that's probably the best approach."
Both Rimm and Dobnig said it is nearly impossible for anyone to suffer adverse effects from too much vitamin D. Those who spend whole days in the sun, such as lifeguards, have vitamin D levels ranging from 45 to 65 ng/mL, said Rimm. "Vitamin D is safe. Hypercalcemia is not a problem, with the rare exception of granulomatous disease," said Dobnig. He added that because vitamin D is a fat-soluble vitamin, it can be given weekly, or even monthly.
Results of two large randomized trials eagerly awaited
Rimm said he hopes ongoing research will inform the vitamin D debate. Data are needed on intermediate end points, such as inflammatory markers and parathyroid hormone, and on "hard" end points, such as coronary artery disease, sudden death, and heart failure, both in primary prevention and in high-risk populations, including those with chronic kidney disease and heart failure.
The results of two large randomized trials are eagerly awaited, he said, including the National Institutes of Health-sponsored VITAL study looking at whether 2000 IU vitamin D and/or 1 g of fish oil (omega-3 fatty-acid supplementation) can reduce the risk of developing heart disease, stroke, or cancer in 20 000 men and women, which is slated to begin in January 2010.
The Thiazolidinedione Intervention with Vitamin D Evaluation (TIDE) study is being coordinated by researchers at McMaster University, Hamilton, ON. This trial is looking at rosiglitazone versus pioglitazone in people with type 2 diabetes at risk of heart disease, but also has a vitamin D versus placebo arm. The primary outcome for the vitamin D arm will be cancer, but there are a number of secondary cardiovascular end points, said Dobnig.
"The evidence for vitamins is not great," Rimm said. "The best thing we can say now is to stop smoking, eat a good diet, and don't be overweight. I think people sometimes lose touch with the most important message of prevention, and jump right to the vitamins thinking that's going to sustain them, so doing what we know first and best is probably the best place to start."
"After that, right now, I think the evidence for vitamin D probably is stronger than the evidence for other vitamins," he concluded.