Vitamin D is fat-soluble vitamin requiring bile for absorption, and occurs naturally in animal foods such as salmon, sardines, egg yolks, cod liver oil and dairy. It can be acquired either by ingestion or by exposure to sunlight. Vitamin D is found primarily in foods of animal origin, unless they are fortified. Vegetables are usually low in vitamin D, except mushrooms which are significant source of absorbable vitamin D.

Vitamin D2 (ergocalciferol) is obtained from plants. Vegetables are usually low in vitamin D, but leafy dark green vegetables and mushrooms are significant non-animal sources. Vitamin D3 (cholecalciferol) is stable to heat, light, and storage and is derived from animal products.

It is estimated that the RDA can be achieved through the exposure of 30% of a person's skin surface to the sun for 30 minutes at moderate latitudes. The darker the skin, the less vitamin D will be produced (up to 95% of UV light is blocked). If longer exposure times are had, even with the darkest skin color, sufficient levels of vitamin D are produced. Glass blocks UV light, so indoor exposure does not help. The RDA for adults is 200 IU; for children, teens and pregnant or lactating women it is 400 IU; for the elderly or those with poor sunlight exposure or living in high northern or southern latitudes, it is 400 - 800 IU. During the winter months especially, it is advisable to supplement vitamin D if sun exposure is low and dietary sources are in question. The vitamin D in human breast milk varies with sun exposure and vitamin D intake.

Unusually high doses may be suggested in some autoimmune conditions. The "no observed adverse effect level" (NOAEL) for vitamin D appears to be at least 10,000IU per day. The lowest observed adverse effect level (LAOEL) is 40,000IU per day. [ Am J Clin Nutr 1999 (69): pp. 842-856] Thus 10,000IU per day is definitely safe (assuming no hypersensitivity) and 40,000IU per day can be a problem. It would be next to impossible for anyone living in a northern area to get too much vitamin D from sunlight and a 4000IU per day supplement. Thus such a supplementation level is safe for anyone who is not hypersensitive to vitamin D.

Commentary by Alan R. Gaby, M.D.
Vitamin D3 is Preferable to Vitamin D2 as a Nutritional Supplement

Vitamin D3 (cholecalciferol) is the "natural" form of vitamin D for humans, since it is produced in the skin after sunlight exposure and is present in foods such as fish and eggs. However, prescription-strength vitamin D preparations available in North America are made exclusively with vitamin D2, a compound produced by irradiating yeast with ultraviolet light. Vitamin D2 is also the main form of vitamin D used in the fortification of milk and other foods. While vitamin D3 and vitamin D2 are both biologically active, there are important differences between them. A recent review article summarized these differences and concluded that vitamin D2 should no longer be used as a nutritional supplement or in food fortification.1

One of the differences between vitamin D3 and vitamin D2 is that the former is considerably more potent. These two forms of vitamin D have long been considered to be biologically equivalent and of equal potency, but that belief is based on an old and relatively insensitive measure of vitamin D activity: the capacity to prevent rickets in experimental animals. More recently, it has become clear that vitamin D3 is much more effective than vitamin D2 at raising the serum concentration of 25-hydroxyvitamin D (25-(OH)D) which is considered a reliable indicator of vitamin D status. In one study, while both types of vitamin D raised the serum 25-(OH)D concentration by the same amount initially, 25-(OH)D levels continued to rise for 14 days after vitamin D3 supplementation. In contrast, after vitamin D2 supplementation, initially elevated 25-(OH)D levels fell rapidly and were not different from baseline at 14 days. According to calculations based on the area under the serum 25-(OH)D concentration-time curve, vitamin D3 is at least 3.4 times as potent as vitamin D2, and may be as much as 9.4 times as potent. 2

A second difference between vitamin D3 and vitamin D2 is in their metabolism. Vitamin D2 is metabolized in large part to 25-(OH)D2, which does not bind as efficiently to vitamin D binding protein in plasma as does the respective vitamin D3 metabolite, 25-(OH)D3. Consequently, the availability of vitamin D2 to some tissues may be lower than that of vitamin D3. Moreover, because of its reduced affinity for vitamin D binding protein, 25-(OH)D2 has a shorter half-life than 25-(OH)D3 does, which might explain the greater potency of vitamin D3.

In addition to its lower bioactivity, vitamin D2 is less stable than vitamin D3, particularly on exposure to variations in temperature and humidity. Consequently, vitamin D2 has a shorter shelf life than vitamin D3. Because of its poor stability, vitamin D2 preparations might contain relatively high concentrations of toxic degradation products.

Another problem associated with use of vitamin D2 supplements is that commonly used laboratory tests do not detect 25-(OH)D2 in the blood as efficiently as they detect 25-(OH)D3. These laboratory tests may therefore underestimate vitamin D status in patients being treated with vitamin D2, potentially leading to an unwarranted increase in the dosage and subsequent vitamin D toxicity.

Because of the disadvantages associated with the use of vitamin D2, and considering that vitamin D3 is the form of vitamin D that occur naturally in humans, the authors of the review article argued that vitamin D3 should be used for routine vitamin D supplementation. They pointed out, however, that patients with hypoparathyroidism or other vitamin D-responsive conditions who are well controlled on high-dose vitamin D2 should probably not have their regimens changed.

When switching from high-dose vitamin D2 to vitamin D3, it is important to remember that vitamin D3 is considerably more potent than vitamin D2. A 50,000-IU dose of vitamin D2 is roughly equivalent to 5,000 to 15,000 IU of vitamin D3. Failure to consider this difference in potency when using vitamin D3 in place of vitamin D2 could place the patient at risk of developing vitamin D toxicity. Because the relative potency of these two forms of vitamin D may differ substantially from one person to the next, patients being switched from vitamin D2 to vitamin D3 should have their serum 25-(OH)D level monitored until their optimal dosage is determined. That caveat does not apply to vitamin D3 doses of 2,000 IU per day or less, which are considered safe for the general population.

References:
1 Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr 2006;84:694-7.
2 Armas LAG, et al. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab 2004;89:5387-91.