American College of Physicians: Internal Medicine — Doctors for Adults ®

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Experts debate pros, cons of vitamin D

From the November ACP Internist, copyright 2009 by the American College of Physicians

By Stacey Butterfield

After spending much of its history as an obscure nutrient, vitamin D has been getting sensational news coverage lately. But it’s not just the media who’ve gotten excited; even a quick search of recent medical literature brings up ominous warnings about the relationship between the vitamin and our nation’s health.

Two years ago, nutritionists wrote an editorial for the American Journal of Clinical Nutrition about “the urgent need to recommend an intake of Vitamin D that is effective.” In March 2009, an analysis published in the Archives of Internal Medicine reported a “growing epidemic of vitamin D insufficiency” in the U.S. population. Most recently, a study in Pediatrics concluded that vitamin D deficiency is “common in the general U.S. pediatric population and is associated with adverse cardiovascular risks.”

Illustration by David Cutler

Illustration by David Cutler



Reports such as these seem likely to send physicians rushing out to consume as much D as they can find and revise guidelines and recommendations so that patients do the same. And some nutrition experts would, more or less, advocate that course of action.

But, in the eyes of others knowledgeable in the field, the subject is a little more complicated. They see risks and costs to be considered and evidence to be gathered before the medical establishment goes all out for vitamin D.


“The assay for 25-hydroxyvitamin D is now the most ordered assay in the U.S. Medicare does not condone screening and I must admit, nor do I.”
— Michael F. Holick, MD, PhD


Good associations

Michael F. Holick, MD, PhD, is in the vanguard of the pro-D forces. “We’re now beginning to realize that vitamin D deficiency may be the most common medical condition in both children and adults worldwide, including the U.S.,” said Dr. Holick, a professor of medicine, physiology and biophysics at Boston University School of Medicine who wrote a review on the subject for The New England Journal of Medicine in July 2007.

He offered a long list of medical problems that can be possibly prevented by vitamin D supplementation: schizophrenia; diabetes; multiple sclerosis; colorectal, breast and prostate cancer; heart attack; stroke; even respiratory tract infections. “We believe that being vitamin D sufficient will help improve immune function and help fight infections, including possibly influenza virus,” he said.

That’s in addition to the better-known effects of vitamin D on bone health. A conference convened in September 2007 by the National Institutes of Health concluded that combined calcium and vitamin D supplementation decreases the risk of fracture and increases bone mineral density. See recommended doses of calcium and vitamin D intakes from PIER.

The evidence review assessed at the conference did not endorse any other benefits of vitamin D, however. “The review focused only on bone health because initial evaluation of the literature indicated that the data were insufficient to examine other health outcomes, such as cancer, autoimmune disorders, and immune function,” explained a paper summarizing the conference that appeared in the August 2008 American Journal of Clinical Nutrition.

That’s still the case today, according to Mary Frances Picciano, PhD, a nutritionist from the NIH who co-authored the summarizing paper.

“There are many interesting studies on vitamin D that have recently hit the press, but most of them are observational studies and epidemiological studies and the results are preliminary. In other words, they serve as the basis of a good hypothesis but they haven’t been studied with the kind of rigor that would be required to make a public health recommendation,” she said.

Because the research is observational instead of controlled, there’s potential for confounding variables. “If you have an indoor sedentary lifestyle and you eat garbage instead of a good diet and you don’t take vitamin supplements and you’re obese, you’re likely going to have health problems. All of those things drive down vitamin D levels,” said Barbara Gilchrest, MD, a professor of dermatology at Boston University who has also written about vitamin D.

Put a number on it

Beyond the debate about whether low vitamin D levels actually cause the many health problems with which they have been associated, experts don’t even agree on what constitutes a low level. The Institute of Medicine currently considers a serum 25-hydroxyvitamin D level of 15 nanograms per milliliter (or 37.5 nanomoles per liter) to be the minimum for sufficiency, but an update of its recommendations is under way right now.

“We know if people have less than 27.5 nanomoles per liter [11 ng/mL], they’re at increased risk for rickets and osteomalacia,” said Dr. Picciano. “Above that, some people have said 37.5 [15 ng/mL]. Some people have said 50 [20 ng/mL]. Some people have said 75 [30 ng/mL]. But none of those higher values have been related to clinical health outcomes.”

For example, in concluding that low levels of vitamin D are associated with metabolic syndrome in children, the recent Pediatrics study used 30 ng/mL as the threshold for vitamin D sufficiency. “[That level] has never been established as the desirable criterion of adequacy of vitamin D in children,” said Dr. Picciano.

Conveniently, on a practice level, it doesn’t really matter what the standard for vitamin D insufficiency is, because none of the experts recommend testing for it. Not that anyone is listening to them. “The assay for 25-hydroxyvitamin D is now the most ordered assay in the U.S.,” said Dr. Holick. “Medicare does not condone screening and I must admit, nor do I.”

Not only are the assays expensive, but they can also be inaccurate, said Dr. Picciano. When new reference standards were released in July, she checked many of the currently available assays and concluded that “they’re not that reliable.”

According to the experts, there’s an easier, cheaper way to determine if your patients are vitamin D insufficient talk to them. “I think you would probably get more information by asking about how they eat, whether they go outside,” she said.

According to Stephanie Atkinson, PhD, a professor and associate chair of pediatrics from McMaster University in Canada who has researched vitamin D, there are three categories of people who are at higher risk of insufficiency: those who don’t get sun exposure, those who don’t consume foods containing vitamin D, and those who have any kind of malabsorption disease.

In addition to patients whose skin actually doesn’t see the sun, either because they stay inside or are extremely vigilant about sunscreen, the first category may include blacks and other populations with highly pigmented skin that absorbs less vitamin D. These patients may also be less likely to consume foods fortified with it.

“Unfortunately, vitamin D is more difficult to get from the regular food in the diet than most nutrients, so we have to rely on fortified foods. Milk has been fortified for years. But if you’re lactose-intolerant like many African-Americans and Asians, you won’t drink milk,” said Dr. Atkinson.

Other fortified foods include orange juice, yogurt, and cereals, and the vitamin exists naturally in some fish, such as salmon, tuna and mackerel. Finding out whether patients are already getting vitamin D should be pretty simple, according to Dr. Atkinson. “The physician should ask those questions: How much sun do you get? Do you eat fortified foods?”

How much?

What you do with the answers is another area of controversy. Dr. Holick advocates large doses of supplements for almost all patients. “Unless you have some reason to believe that they can’t take a vitamin D supplement or a vitamin D treatment, you should assume your patient’s vitamin D deficient and treat them appropriately,” he said.

The IOM has set the reference intakes for vitamin D at 200 International Units (IU) for people up to age 50, 400 IU for 51- to 70-year-olds, and 600 IU for those over 70. However, Dr. Holick believes in going significantly higher.

“You need to fill the tank up, so I typically will give my patients a 50,000-unit dose of vitamin D once a week for eight weeks. That’s the equivalent of taking 6,000 units a day. I switch them after two months to 50,000 units twice a month,” he said.

Such high levels of supplementation make some other experts nervous. “Nobody has really ever studied long-term use of vitamin D supplementation at the levels some people are recommending right now. 1,000 is probably all right, but 2,000, 3,000 might be fine for a year, two years, five years, but I don’t know what’s going to happen in 10 years,” said Dr. Picciano.

One possible risk of heavy vitamin D use is kidney stones. The Women’s Health Initiative, which included a controlled trial of vitamin D taken together with calcium, found a 17% increased risk of kidney stones in the women who were taking 1,000 mg of calcium and 400 IU of vitamin D per day.

The IOM set 2,000 IU per day as the tolerable upper intake level in its 1997 report on dietary reference intakes, for which Dr. Atkinson served as the chair. “You could safely take up to 2,000 a day without worry of any toxicity and probably more, but that has to be defined,” she said. The new IOM report on vitamin D, which could change the recommended intakes, is expected to be released in May 2010.

Split over the sun

In the meantime, there is one way to get the nutrient without any risk of vitamin D toxicity, but it is, if anything, more controversial. “I’ve always been recommending that people should take advantage of the beneficial effect of the sun because it is the major source of vitamin D for humans on this earth,” said Dr. Holick.

“It has been well-established that sunlight causes vitamin D precursor to be produced in the skin and results in higher storage levels of vitamin D,” agreed Dr. Gilchrest. But she is concerned about the other effects of sunlight. “Sun exposure causes DNA damage, causes photoaging, causes basal-cell and squamous-cell cancer and melanoma,” she said.

“I find it very regrettable that in many circles it’s been a conclusion that because there’s a question about whether the world has enough vitamin D, therefore everybody should get more sun exposure,” Dr. Gilchrest added.

Other experts contend that the amount of sun exposure being called for is minor. “Just like everything else in life, moderation. If you know you’re going to be out in a bathing suit and you know you’re going to get a slight sunburn after being out there for 30 minutes, then you only need to be out there for 10 to 15 minutes maximum, exposing arms and legs a couple of times a week, followed by good sun protection,” said Dr. Holick.

And if a problem with the case for vitamin D is its basis in associational studies, that’s true of much of the dermatologic argument against the sun, too, according to Dr. Atkinson. “Again, it’s mostly epidemiological, [the] association between sun exposure and different skin cancers,” she said. “In summer, even in Canada, if you just expose 25% of your skin, if you were quite white-skinned, in four minutes you could make the same amount of vitamin D as popping a pill.”

But Dr. Gilchrest worries that the value of four-minute exposures is not the message that’s getting out to the public. “The people who are paying attention to this message are fair-skinned teenagers and young adults who are already getting sun exposure at that level,” she said. “We’re not talking about people carefully getting their two to five minutes of sun and then putting on their sunscreen. We’re talking about people going to tanning booths.”

Dr. Atkinson agreed that the public health message on vitamin D and sun exposure needs refinement. “I think we need to come to some agreement among all health professionals about what safe sun is. We’re not there yet.”

Given the many issues of contention among vitamin D experts, her statement could just as well apply to the entire discussion of this hot-button nutrient.

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