D is a well known fat soluble vitamin that is important for maintaining calcium
and phosphate homeostasis, mineralization of the bone, and the modulation of
gene expression, cell growth and differentiation.1-3 As it relates
to calcium absorption from the gastrointestinal (GI) tract, vitamin D in the
body must be activated before it can facilitate or increase GI absorption of
D can come from one of three sources.1-3,5,6 The first occurs when the
skin is exposed to sunlight. Ultraviolet (UV) B radiation is able to
penetrate exposed skin to facilitate the conversion of 7-dehydrocholesterol to
previtamin D3 and then on to vitamin D3 or cholecalciferol. The second
way to get vitamin D is through over-the-counter (OTC) supplementation.
Most OTC products and some vitamin D fortified foods contain the same vitamin
D3 or cholecalciferol formed from sun exposure. The third way to get
vitamin D is naturally through the diet. As mentioned above, many vitamin
D fortified foods will contain cholecalciferol. However, plant based
foods also contain vitamin D2 or what is also known as ergocalciferol. It
is important to note here that regardless of the source of vitamin D, none of
them are active or able to directly modulate the absorption of calcium and thus
must become activated through two more steps within the body. This is
best represented by the figure provided below.
first step in the process of activating either ergocalciferol or
cholecalciferol takes place in the liver and is largely unregulated.4 A
hydroxyl (-OH group) is added to carbon number 25 forming 25-hydroxyvitaminD or
what is also known as calcidiol or 25-hydroxycholecalciferol.4 In the
kidney, the newly formed 25-hydroxyvitamin D undergoes a second hydroxylation
reaction on carbon number 1 to form 1,25-hydroxyvitamin D or what is also known
as calcitriol or 1,25-dihydroxycholecalciferol (the active form of vitamin D).4
Depending on the level of regulation or the need for calcium in the blood, the
25-hydroxyvitamin D can be metabolized by 24-hydroxylase to form
24,25-dihdroxycholecalciferol (the inactive form).4
it relates to patients taking phenytoin, it is known that these patients have
lower levels of 25-hydroxyvitamin D, which can begin to manifest as early as 60
days after starting phenytoin.7,8,9 The mechanism for this reduction in
25-hydroxyvitamin D is due to phenytoin's ability to cause a dose-dependent
inhibition of active calcium transport by intestinal epithelial cells (see
figure provided).10 As such patients being managed long-term on phenytoin
for their epilepsy, should probably take 25-hydroxyvitamin D supplementation to
avoid the risk for developing osteomalacia.8,9
- National Institutes of Health: Office of Dietary Supplements.
Dietary Supplement Fact Sheet: Vitamin D. Last Accessed: June 10,
- Institute of Medicine, Food and Nutrition Board. Dietary
Reference Intakes for Calcium and Vitamin D. Washington, DC: National
Academy Press, 2010.
- Cranney A, Horlsey T, O'Donnell S et al. Effectiveness and
safety of vitamin D in relation to bone health. Evid Rep Technol Assess
(Full Report) 2007;158:1-235.
- DeLuca HF. Metabolis and molecular mechanism of action of vitamin D: 1981. Biochem Soc Trans 1982;10:147-158. PubMed
- Holick MF. Vitamin D deficiency. N Engl J Med 2007;357(3):266-281.
- Calvo MS, Whiting SJ, Barton CN. Vitamin D fortification in the
United States and Canada: current status and data needs. Am J Clin Nutr
- Gough H, Goggin T, Bissessar A et al, A comparative study of the
relative influence of different anticonvulsant drugs, UV exposure and
diet on vitamin D and calcium metabolism in out-patients with epilepsy.
Q J Med 1986;59:569-77.
- Krishnamoorthy G, Nair R, Sundar U et al. Early predisposition
to osteomalacia in Indian adults on phenytoin or valproate monotherapy
and effective prophylaxis by simultaneous supplementation with calcium
and 25-hydroxy vitamin D at recommended daily allowance dosage: a
prospective study. Neurol India 2010;58:213-9.
- Espinosa PS, Perez DL, Abner E et al. Association of
antiepileptic drugs, vitamin D, and calcium supplementation with bone
fracture occurrence in epilepsy patients. Clin Neurol Neurosurg
- Von Borstel Smith M, Crofoot K, Rodriguez-Proteau R et al.
Effects of phenytoin and carbamazepine on calcium transport in Caco-2
cells. Toxicol In Vitro 2007;21:855-62.