Abstracts

Rationale: Vitamin D3 is a fat soluble steroid hormone, which plays a critical role in cardiac, muscle, bone and brain function. Vitamin D3 affects gene expression via a ligand specific nuclear receptor, and affects calcium and chloride flux across neuronal membranes. Vitamin D3 demonstrates acute anticonvulsant effects in mouse and rat models. Little information is known about the antiepileptic effect of Vitamin D3 in humans. The purpose of this study is to evaluate the safety, tolerability and preliminary efficacy of Vitamin D3 5,000 IU/day. In addition, we explored the effect of Vitamin D3 on RMSSD, a measure of heart rate variability, which is a bio-marker of risk in heart failure and sudden death in epilepsy. Methods: Pilot, open label safety and preliminary efficacy study of Vitamin D3 in patients with drug-resistant epilepsy. At baseline, vitamin D3 levels, vital signs, Heart Rate Variability, mood, and key metabolic indices were evaluated. Subjects returned after a 4-week baseline, and started Vitamin D3 5,000 IU/day, and were evaluated at 6 and 12 weeks. The effect of Vitamin D3 on calcium, vitamin D3 levels, vital signs, Beck Depression Scale, seizure frequency and heart rate variability were evaluated. Results: Eleven subjects have been enrolled to date. Vitamin D3 5,000 IU/day was well tolerated. No adverse events related to supplementation were noted. Vitamin D levels rose substantially after supplementation, but no toxic levels of Vitamin D3 (defined as > 100 ng/ml) were recorded. Vitamin D3 levels after 12--weeks of supplementation ranged from 50 to 77 ng/ml. Preliminary assessment of RMSSD, a biomarker associated with risk of heart SUDEP improved. Conclusions: High-dose Vitamin D3 (5,000 IU/day) was safe and well tolerated. Vitamin D levels after supplementation did not exceed the toxic range (> 100 ng/ml). Vitamin D supplementation was not associated with any adverse effect on blood pressure, vital signs, mood, or chemistry levels.  Vitamin D supplementation was associated with improvements in RMSSD, a potential biomarker of SUDEP. Funding: Supported by grants by Beverly and James Peters, and Linda and Robert Brill to the UCLA School of Medicine for epilepsy research.