High-Dose Oral Vitamin D3 Appears Safe and Well-Tolerated in Epilepsy

Investigators evaluated the safety and tolerability of oral Vitamin D3 5000 IU/d in patients with drug-resistant epilepsy.

Vitamin D3 in high doses was safe and well-tolerated in patients with epilepsy and never exceeded toxic levels, according to study results published in Epilepsy & Behavior.

Researchers sought to examine the tolerability of vitamin D3 in an ongoing trial of vitamin D3 5000 IU/d intended to reduce seizures in drug-resistant epilepsy. Inclusion criteria were that participants should have ≥1 focal onset or generalized tonic-clonic seizure per month and must have been treated with ≥2 antiepileptic drugs (AEDs) alone or in combination at effective doses without becoming seizure-free. Participants were to maintain a seizure calendar, and no changes in AED doses were allowed during the study.

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There was a 4-week baseline period followed by a 12-week treatment period. During the treatment period, participants were administered 1 vitamin D3 5000 IU capsule daily. Blood tests for vitamin D level and blood chemistries (calcium, blood urea nitrogen, and creatinine) were performed at study entry and at each treatment visit.

Blood levels were also obtained at the beginning and end of the study for the major AEDs (ie, carbamazepine, phenytoin, lamotrigine, phenobarbital, or valproic acid) to determine the effect of vitamin D on major epilepsy drugs and their levels. Vitamin D insufficiency was defined as a serum 25-hydroxyvitamin D (25, OH vitamin D) level of <20 ng/mL. Changes in seizure rate/d and vitamin D levels were evaluated at each visit relative to baseline.

A total of 11 participants were enrolled, and 9 completed the treatment period. Vitamin D3 was well-tolerated, and no treatment-related adverse events were reported. Vitamin D3 normalized in all 5 participants with insufficiency by 6 weeks. Median vitamin D3 levels increased from a baseline level of 18.3 (range: 7-39.4) ng/mL to 43.4 (range: 31-80) ng/mL at 6 weeks and 53 (range: 47-87) ng/mL at 12 weeks.

The change in serum 25, OH vitamin D3 levels were significant (P =.0078 at 6 weeks and P =.0039 at 12 weeks). There were no changes in blood chemistry. The median percentage reduction in seizure frequency was 26.9% at 6 weeks and 10.7% at 12 weeks.

Although no toxic levels were reported, vitamin D3 was not associated with a significant reduction in seizures, contrary to reports from preclinical and early clinical studies.

Researchers concluded that vitamin D3 was well-tolerated in epilepsy. Also, as the study is ongoing, further information is anticipated regarding the role of vitamin D3 in epilepsy.


DeGiorgio CM, Hertling D, Curtis A, Murray D, Markovic D. Safety and tolerability of vitamin D3 5000 IU/day in epilepsy. Epilepsy Behav. 2019;94:195-197.