During the past decade it has become clear that vitamin D deficiency is relatively common among the general population. Potential consequences of low vitamin D status include accelerated bone loss, an increased risk of falls among the elderly, decreased resistance against influenza and other types of infection, an possibly an increased risk of developing cancer and certain autoimmune diseases. In addition, evidence has accumulated that the amount of vitamin D needed to prevent a deficiency is higher than previously believed. Whereas 400 IU/day had long been thought to be sufficient for most people, it is now known that 800 IU/day is needed to slow the progression of osteoporosis and to prevent falls.
In recent years, a number of researchers have recommended a redefinition of vitamin D deficiency, and many laboratories have changed their reference range for serum 25-hydroxyvitamin D (25[OH]D) to comply with that recommendation. Historically, the lower limit of normal for 25(OH)D has been 10-15 ng/ml (25-37.5 nmol/L), depending on the laboratory. Many laboratories are now defining vitamin D deficiency as a serum 25(OH)D level < 20 ng/ml (< 50 nmol/L), and vitamin D insufficiency (mild vitamin D deficiency) as a level < 30 ng/ml (< 75 nmol/L).1 It has also been suggested that increasing serum 25(OH)D to an "optimal" level could improve a wide range of health outcomes, including better bone and dental health, fewer falls and fractures, and possible protection against cancer and autoimmune disease. A review article concluded that a protective effect began at a 25(OH)D concentration of 30 ng/ml (75 nmol/L), and that the best outcomes were seen in people with levels of 36-40 ng/ml (90-100 nmol/L).2
If one accepts these new laboratory criteria, then inadequate vitamin D status emerges as a major epidemic, being present in 40-50% of participants in many studies. Moreover, the amount of supplemental vitamin D needed to achieve "adequate" or "optimal" vitamin D status is well above 800 IU/day in many cases. For example, it has been estimated that only 50% of people who take 1,000 IU/day of vitamin D will attain a serum 25(OH)D level of 30 ng/ml (75 nmol/L). The estimated dosage needed to achieve a level of 30-32 ng/ml (75-80 nmol/L) in nearly all healthy adults has ranged from 1,644 IU/day to more than 3,440 IU/day in different studies.3,4 Even larger doses would be needed to achieve an "optimal" level of 36-40 ng/ml (90-100 nmol/L). Based on these findings, some practitioners are recommending long-term supplementation with 2,000, 5,000, or even 10,000 IU/day of vitamin D for many of their patients.
A recurring theme in nutritional medicine is that the dosages of various nutrients needed to promote optimal health are often greater than the amounts needed to prevent a frank deficiency. The same is almost certainly true with respect to vitamin D. However, considering that a substantial minority of the population would need to consume potentially toxic doses of vitamin D in order to achieve a serum 25(OH)D level of at least 30 ng/ml (75 nmol/L), the evidence supporting the benefit and safety of high-dose vitamin D warrants scrutiny.
After reviewing the available research, I have reached several conclusions. First, serum 25(OH)D is not an entirely reliable indicator of vitamin D status. Second, an increase in the lower end of the reference range for serum 25(OH)D may not be appropriate for some populations and some individuals. Third, the evidence supporting the benefit of pushing serum 25(OH)D to an "optimal" level is weak. Fourth, the evidence supporting the long-term safety of vitamin D in doses greater than 2,000 IU/day is weak. Of particular concern is the possibility that long-term use of high doses might promote the development of atherosclerosis or kidney stones. Fifth, the physiological effects of sunlight exposure differ from those of vitamin D supplementation. One implication of that fact is that vitamin D supplementation may not duplicate the beneficial effects of sunlight exposure. Moreover, evidence regarding the safety of vitamin D synthesized in the skin might not apply to orally administered vitamin D.
These conclusions do not negate the observations that large doses of vitamin D have been safe and effective for some patients (such as patients with malabsorption, prostate cancer, or drug-induced vitamin D deficiency). However, routine use more than 2,000 IU/day of vitamin D for the sole purpose of achieving a target 25(OH)D level may be unwarranted. The evidence that has led me to these conclusions is reviewed below.
Assessment of Vitamin D Status
Although 1,25-dihydroxyvitamin D (1,25[OH]2D) is the biologically active form of vitamin D, serum 1,25(OH)2D is not a reliable indicator of vitamin D status. That is because vitamin D deficiency results in a compensatory increase in the concentration of parathyroid hormone, which increases the renal production of 1,25(OH)2D. Consequently, serum 1,25(OH)2D levels are often normal or elevated in people with vitamin D deficiency.5
