Interactions with Vitamin D

Antacids that bind phosphate may alter the levels, metabolism, and availability of vitamin D. There is a case report of osteomalacia in a patient that consumed large amounts of antacids (Godsall et al. 1984). Aluminum-containing antacids may also increase the risk of fractures from osteomalacia resistant to the administration of vitamin D; this is of particular concern for people at risk for aluminum toxicity including newborns, elderly, and people with kidney or liver disease (Henning 1989).

Doxorubicin

The hormonal form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), interacted synergistically with doxorubicin by increasing the cytotoxic activity of the drug against breast cancer cells in vitro (Ravid et al. 1999).

Estrogens; Progestins

In one study, both total and free 1,25-(OH)2D concentrations increased in women within 5 years of menopause who were being treated with unopposed estrogen for three cycles (Bikle et al. 1992). With the addition of progestin, the levels of vitamin D returned toward baseline. Progestin may antagonize some of the beneficial effects of estrogen on calcium balance and bone metabolism; it is not clear if vitamin D supplementation will overcome this effect.

Thiazide Diuretics

Thiazide diuretics enhance the biological activity of vitamin D and increase the risk of hypercalcemia (Hines Burnham et al 2000).

Verapamil

Verapamil may induce parathyroid hormone (PTH) resistance accompanied by a decrease in 1,25(OH)D3 levels (Fox 1988). Studies in rats have demonstrated that the negative correlation between PTH and vitamin D levels is significant. However, this interaction does not appear to have long-term effects on calcium homeostasis because of a dose-dependent increase in duodenal absorption of calcium.

References

Bikle DD, Halloran BP, Harris ST, Portale AA. Progestin antagonism of estrogen stimulated 1,25-dihydroxyvitamin D levels. J Clin Endocrinol Metab. 1992;75(2):519-523.

Fox J. Verapamil induces PTH resistance but increases duodenal calcium absorption in rats. Am J Physiol. 1988;255(5):E702-707.

Godsall JW, Baron R, Insogna KL. Vitamin D metabolism and bone histomorphometry in a patient with antacid-induced osteomalacia. Am J Med. 1984;77(4):747-750.

Henning HV. Aluminum toxicity [in German]. Klin Wochenschr. 1989;67(24):1221-1228.

Hines Burnham, et al, eds. Drug Facts and Comparisons. St. Louis, MO:Facts and Comparisons; 2000:9.

Ravid A, Rocker D, Machlenkin A, et al. 1,25-Dihydroxyvitamin D3 enhances the susceptibility of breast cancer cells to doxorubicin-induced oxidative damage. Cancer Res. 1999;59:862-867.

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