Vitamin D And Hypercalcemia

Calcifediol Supplementation Toxicity

Vitamin D Supplementation: Concerns about Toxicity

Vitamin D (calciferol) is so essential to health that all vertebrates can produce this nutrient endogenously when the skin is exposed to ultraviolet light (Hoffmann, Senior, Mager 2015; Standing Committee et al. 1997). Vitamin D can also be obtained from fish and modern-day fortified food products. When exposed to sunlight, 7-dehydrocholesterol in the skin is converted to previtamin D3 (cholecalciferol) and then vitamin D3, which is then hydroxylated by liver enzymes to form 25-hydroxyvitamin D3 (25(OH)D3; calcifediol). The biologically active form is finally created when calcifediol is hydroxylated once more by a mitochondrial enzyme in the kidneys to form 1,25-dihydroxyvitamin D (1,25(OH)2D; calcitriol).

The two most common forms of dietary vitamin D supplementation are cholecalciferol and calcifediol, but the biological activity of the latter is 5 times that of the former (Standing Committee et al. 1997). The downstream effect of 1,25(OH)2D production is increased absorption and utilization of dietary calcium and phosphorus and increased plasma levels of these minerals. As calcium plasma levels rise, and to a lesser extent phosphorus plasma levels, the same kidney cells will reduce calcitriol production through a parathyroid hormone-dependent feedback loop. Deluca and colleagues (2011) have suggested that vitamin D toxicity is probably the result of high plasma concentrations of calcium and phosphorus, rather than a direct result of excess vitamin D In support of this theory, vitamin D toxicity results in calcification of a number of tissues (hypercalcemia), including the kidneys, heart, major blood vessels, lungs, and skin. Vitamin D toxicity can only occur in healthy people through the excess consumption of fish oils or supplements, not through excess exposure to sunlight.

Since dietary and endogenous sources of vitamin D contribute to calcifediol serum concentrations, physicians interested in monitoring a patient's vitamin D status will quantify this marker (Standing Committee et al. 1997). The normal range for the general population varies depending on the geographic location, with sunnier locations having a higher range; however, a calcifediol concentration below 27.5 nmol/liter (11 ng/ml) in young children and infants represents vitamin D deficiency. The elderly represent another susceptible group and both plasma calcifediol and parathyroid hormone levels are checked for vitamin D deficiency. Current recommendations are for everyone to get sufficient exposure to sunlight, but when this is not possible, the diet should be supplemented with 200 international units (IU) per day for all ages up to 50 years of age. For individuals between the ages of 51 and 70, or above 70 years of age, the diet should be supplemented with 400 or 600 IU per day, respectively.