Is widespread vitamin D supplementation advisable for the adult population?
Widespread supplementation of the adult population with vitamin D is advisable because doing so restores the condition; under which human physiology evolved, is efficacious, and is safe.
Let's look first at the physiology. Vitamin D is normally made in the
skin upon exposure to UV-B radiation. Humans evolved in equatorial East Africa wearing no clothes and would have received extensive sun exposure year-round. Data obtained in dark-skinned agricultural workers in the tropics or ethnic groups such as the Maasai in East Africa indicate that primitive serum 25-hydroxyvitamin D (25[OH]D) levels would have ranged from 50 to 80 ng/mL. Pharmacokinetics studies show that maintenance of such levels requires 6,000-10,000 IU vitamin [D.sub.3] per day. These data are consistent with studies showing that a single 15-minute July sun exposure is equivalent to a single oral dose in the range of 10,000-25,000 IU. Even in Third World countries, few individuals get such sun exposure today, because of clothing, latitude, and indoor work.
Providing vitamin D supplements to adults has also been shown to be effective in reducing the risk of a variety of chronic diseases. There are approximately 40 randomized controlled trials of vitamin D supplementation, the vast majority of which show clinically important decreases in health risks.
This extraordinary breadth of effect is explained by two key insights from cell biology. First, most tissues must continuously access the information stored in the genetic code for everyday physiologic functions. Second, 1,25 dihydroxyvitamin D (1,25[[OH.]sub.2]D), synthesized within the cell from serum 25(OH)D, is an essential cofactor for cell access to this stored genetic information. Vitamin D does not so much cause physiological effects (not even calcium absorption); rather, it enables various body tissues to perform their specialized functions under physiologic controls. While a cancer-protective effect may seem surprising, it is helpful to note that there is a solid body of basic science in support: Vitamin D deficiency greatly enhances carcinogenesis in several animal models.
Just as important, vitamin D has been shown to be safe. When any intervention is applied to the general population, there is always the chance of rare reactions or of bad outcomes in some system other than the ones for which supplementation is promoted. But we can provide considerable reassurance by evaluating individuals who naturally have high blood levels.
Both native African populations and outdoor summer workers in temperate latitudes typically have values in the range of what is likely to have been the primitive norm. The Maasai, particularly, have been subject to extensive biomedical study, without revealing evidence of untoward consequences of their vitamin D status. Moreover, there has never been a case of vitamin D intoxication from sun exposure. In cases of reported vitamin D intoxication, there are no instances where the serum 25(OH)D level was below 200 ng/mL, and none where the daily intake was below 30,000 IU Additionally, there is the "Stosstherapie" experience of Eastern Europe in the middle part of the last century where it was common to give infants, population-wide, 600,000 IU vitamin [D.sub.3] three times a year (a dose of approximately 4,000-5,000 IU/day). This regimen, while not recommended today, was nevertheless well tolerated.
Critics who say "Yes, the data look promising, but we need more evidence before supplementing at a population level" seem to be unaware of the massive level 1 evidence showing clearly important benefits. The risk of harm from not supplementing seems far greater than possible risk of harm from a judicious program of supplementation.
No: Caution Is Appropriate.
Extrapolation from the results of vitamin D interventional studies has led some advocates to propose widespread vitamin D supplementation for the U.S. population. This view assumes that the benefit of wide-spread supplementation is significantly greater than the potential risk. Widespread supplementation would reduce the need to check serum 25-hydroxyvitamin D levels periodically in adults, thereby reducing health care costs, and bypass issues related to the accuracy of vitamin D measured in different assays. Advocates argue that the risk of vitamin D toxicity, and potential harm, with supplemental doses of less than 2,000 IU daily, or sometimes more, is very low.
But there are several concerns regarding widespread vitamin D supplementation. First, individuals vary widely in their ability to synthesize, absorb, store, and metabolize vitamin D. Genetic differences affecting vitamin D metabolism require that some individuals must take much higher doses of vitamin D than the average adult to achieve an optimal vitamin D level of 30 ng/mL or greater, and also that others may take less. These interindividual differences make it difficult to select a single dose of vitamin D that will meet the needs of the entire population.
Second, the potential for vitamin D toxicity exists with increased supplemental doses, even though this risk is relatively uncommon. Intermittent dosing with very high doses of vitamin D is increasingly popular, with greater potential for toxicity if high-dose supplementation is continued longer than needed, or not monitored. Vitamin D toxicity takes weeks to months to resolve once it develops, and increases the risk of hypercalcemia, hypercalciuria, renal insufficiency, nephrocalcinosis, or kidney stones.
Third, some individuals treated with increased vitamin D supplementation develop unsuspected hypercalciuria and increased kidney stone risk with-out vitamin D toxicity. Hypercalciuria was seen in some of the early studies of high-dose calcium and vitamin D supplementation in postmenopausal osteoporotic women. The Women's Health Initiative (WHI) calcium and vitamin D intervention study reported a 17% increased risk of kidney stones in subjects advised to take vitamin D 400 IU and elemental calcium 1,000 mg each day over 7 years (N. Engl. J. Med. 2006;354:669-83). The number of subjects developing kidney stones in the WHI was a small percentage of the total number of women treated, but this study suggests that implementation of recommendations for widespread vitamin D supplementation in the U.S. population may cause some individuals to form kidney stones.
Finally, widespread vitamin D supplementation could potentially accelerate coronary artery or other vascular disease in patients with moderate to severe chronic kidney disease, especially when renal insufficiency is not recognized, or in patients with systemic disorders characterized by vascular inflammation, such as rheumatoid arthritis, lupus, or diabetes mellitus. Patients with these disorders may metabolize vitamin D supplements differently than healthy adults.
While optimization of vitamin D levels is likely to have significant benefit for most healthy individuals, proper caution should be exercised before recommending widespread vitamin D supplementation to all adults.
Caution is appropriate because of variation in the way individuals metabolize vitamin D, the small risk of vita min D toxicity with long-term high-dose supplementation, the risk of unsuspected hypercalciuria and consequent decrease in kidney function or development of kidney stones in some patients, and the potential worsening of cardiovascular disease in those with chronic kidney disease or systemic inflammatory disorders.
BY ROBERT P. HEANEY, M.D.
Dr. HEANEY is John A. Creighton University Professor and professor of medicine in the division of endocrinology at Creighton University in Omaha, Neb. He was a member of the Institute of Medicine s Calcium and Related Nutrients Panel of the Food and Nutrition Board, which set the intake recommendations for vitamin D in 1997. He reported no financial disclosures.
BY BART L. CLARKE, M.D.
Dr. Clarke is an Associate Professor of Medicine in the Division of Endocrinology, Diabetes, Metabolism, and Nutrition at the Mayo Clinic in Rochester, Minn. He has done extensive research on osteoporosis. He reported no financial disclosures.
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|Author:||Heaney, Robert P.; Clarke, Bart L.|
|Publication:||Internal Medicine News|
|Date:||Aug 1, 2010|
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