Vitamin D and UV: Risks and Benefits

History

Vitamin D is a fat-soluble prohormone that plays an important role in calcium and phosphorus homeostasis as well as in many organ systems throughout the body. There are two major physiologically relevant forms of vitamin D: D ₂ (ergocalciferol) and D ₃ (cholecalciferol). Vitamin D ₂ , which is present in yeast and mushrooms, is derived from ergosterol, a yeast and plant sterol. Vitamin D ₃ is produced photochemically in the skin from 7-dehydrocholesterol, a cholesterol precursor.

The modern history of vitamin D began in the mid-1800s, when it was noticed that city children were more likely to have rickets than rural children. Half a century later, Palm reported that children raised in sunny climates virtually never developed rickets. McCollum isolated vitamin D, and Windaus its precursors, receiving the Nobel Prize.

Sources and metabolism of vitamin D

In humans, vitamin D is obtained naturally through two sources, diet and sunlight. Very few foods inherently contain significant amounts of vitamin D. Fatty fish like salmon, tuna, and mackerel, as well as fish liver oils are among the best sources, providing 200 to 1600 IU per serving. Beef liver, cheese, and egg yolks provide small amounts of vitamin D – 12 to 20 IU per serving – and some mushrooms contain variable amounts. The majority of dietary vitamin D in countries like the United States and Canada comes from foods such as milk, milk products, juices, and cereal products that are fortified with vitamin D. One 8 ounce serving of fortified milk or orange juice in the United States provides approximately 100 IU of vitamin D ( Table 60.1 ).

The major natural source of vitamin D in humans is from the exposure of skin to sunlight. UVB radiation is absorbed by cutaneous 7-dehydrocholesterol to form pre-vitamin D ₃ ( Fig. 60.1 ). This process largely occurs in the stratum basale and stratum spinosum, where 7-dehydrocholesterol is the most concentrated. Pre-vitamin D ₃ undergoes a temperature-dependent isomerization to form vitamin D ₃ , which is then hydroxylated by the liver to 25-hydroxyvitamin D [25(OH)D] via the 25-hydroxylase enzyme. An additional hydroxylation by the kidney via the 1α-hydroxylase enzyme is necessary to produce the physiologically active vitamin D metabolite, 1α,25-dihydroxyvitamin D [1,25(OH) ₂ D], which is best known for promoting intestinal absorption of calcium and phosphorus, decreasing their clearance from the kidney, and promoting bone mineralization.

In addition to foods and sunlight, vitamin D is also available in supplement form as D ₂ or D ₃ . Comparisons between the two forms have shown D ₂ to have a shorter shelf-life, diminished binding of its metabolites to vitamin D binding protein in plasma, and less efficacy in raising and maintaining serum vitamin D metabolite levels. Given these findings, vitamin D ₃ is preferred to D ₂ for supplementation.

Minimal winter sunlight exposure reaches the lower epidermal layers, and therefore little vitamin D is produced in the wintertime. Melanin, which is produced by melanocytes located in the stratum basale, also affects the quantity of vitamin D produced by absorbing UVB. Melanin concentration determines the amount of UVB that can interact with the 7-dehydrocholesterol in the lower epidermal layers, though it does not change the capacity to produce vitamin D; individuals with darker skin pigmentation may need three to six times longer exposure to produce the same amount of pre-vitamin D as those with fair skin. Skin from older individuals contains less substrate for pre-vitamin D synthesis, and they may produce up to four times less pre-vitamin D than their younger counterparts.

Vitamin D in health and disease

Though 25(OH)D has low biological activity, its serum concentration, which can be measured in commercial laboratories, is the most widely used biomarker for an individual's vitamin D status. 25(OH)D levels have been correlated with important health endpoints ( Table 60.2 ); the levels are commonly reported as either nmol/L or ng/mL ( Table 60.3 ). One complication in determining vitamin D status is that there is variability among the laboratories that conduct the analyses as well as in the various available assays. However, a new standard reference material for 25(OH)D became available in July 2009, which should allow for more standardization across laboratories.