Vitamin D in food and supplements

Vitamin D status continues to decline in the United States because of lifestyle factors such as decreased outdoor activity (1). Exposure to sunlight is one of the major determinants of an individual’s vitamin D status. Because the amount of sunlight necessary for optimal vitamin D status varies by individual factors (skin tone, adiposity, age), latitude, season, and time of day, and because of concerns over skin cancer risk, it is difficult to recommend increased exposure to sunlight as a public health strategy to improve vitamin D status in the US population. Therefore, there has been increased interest in improving vitamin D status by either recommending vitamin D supplement use or fortifying foods with vitamin D. Some foods such as meat, fish, and eggs contain vitamin D naturally as the hydroxylated vitamin D metabolite 25-hydroxyvitamin D [25(OH)D3]. However, it is unknown whether 25(OH)D3 found in foods or supplements has the same impact on vitamin D status compared with vitamin D3 (cholecalciferol). For more clarity on this issue, Cashman et al (2), in this issue of the Journal, performed a randomized controlled clinical trial to evaluate the relative potency of oral supplementation with 25(OH)D3 compared with vitamin D3 in raising total serum 25-hydroxyvitamin D [25(OH)D] in adults. They found that supplementation with 25(OH)D3 resulted in 4–5 times higher serum 25(OH)D concentrations compared with supplementation with vitamin D3. The authors concluded that the ability of foods rich in 25(OH)D3 to improve vitamin D status may have been underestimated. These findings not only allow for more accurate assessment of vitamin D activity in specific foods such as meat but also provide an opportunity to evaluate enrichment of meat and dairy products with 25(OH)D3 by supplementing animal feed with vitamin D3 and/or 25(OH)D3. There has been a debate regarding the form of vitamin D that should be used for food fortification or supplements. Vitamin D exists in 2 forms, ergocalciferol or cholecalciferol. Ergocalciferol (vitamin D2) is converted from ergosterol found in fungi or yeast on exposure to UVB light. Similarly, cholecalciferol (vitamin D3) is converted from 7-dehydrocholesterol found in human skin on exposure to UVB light. Early clinical studies have suggested that cholecalciferol is superior to ergocalciferol in sustaining higher serum 25(OH)D concentrations (3, 4). In this issue of the Journal, Tripkovic et al (5) conducted a systematic review and meta-analysis of 10 randomized controlled trials in humans that studied the serum 25(OH)D response to ergocalciferol compared with cholecalciferol. The authors found a significant mean difference of 15 nmol/L change in serum 25(OH)D that favored cholecalciferol compared with ergocalciferol supplementation. When the authors examined studies of bolus dosing of vitamin D, they similarly found a greater increase in serum 25(OH)D concentrations with cholecalciferol compared with ergocalciferol. These results suggest that cholecalciferol may be the preferred form of vitamin D for use in supplements or for use in food fortification. Why has there been debate over the issue of ergocalciferol compared with cholecalciferol? Ergocalciferol was first introduced in 1941 as a prescription drug in the United States for the treatment of rickets (6). Until recently, ergocalciferol (eg, 50,000-IU capsules) has been the only high-dose vitamin D therapy available to physicians in the United States and has been commonly used to treat vitamin D insufficiency (7). However, cholecalciferol has now become available in higher dose strengths both by prescription and over-the-counter as a supplement in the United States. Most of the evidence reviewed by The Endocrine Society in its clinical practice guideline on vitamin D and by the Institute of Medicine in the Dietary Reference Intakes for calcium and vitamin D were based on studies that used cholecalciferol (8–10). Taken together, the data on increased bioavailability of cholecalciferol, coupled with emerging clinical trial evidence, suggest that cholecalciferol may be superior to ergocalciferol for treatment and prevention of vitamin D insufficiency. There remains controversy regarding the magnitude of vitamin D deficiency in the United States and whether vitamin D confers nonskeletal health benefits. The use of a serum 25(OH)D concentration ,50 nmol/L to define vitamin D deficiency places approximately one-third of the US population at risk of vitamin D deficiency (1). Improving vitamin D status by public health policies to increase food fortification or to recommend vitamin D supplements to those at highest risk of vitamin D deficiency seems prudent. Results of ongoing trials of vitamin D supplementation in various chronic health conditions will help to establish the potential roles for vitamin D in the prevention and treatment of disease and thus will guide future supplementation strategies.