Unraveling the nutritional challenges in epilepsy: Risks, deficiencies, and management strategies: A systematic review

Table 1 Quality assessment of randomized controlled trials on vitamin supplementation in epilepsy using the Cochrane risk of bias tool¹

Ref.	Vitamin studied	Sample size (n)	Risk of bias (Cochrane tool)	Main outcome	Statistical findings (P value, 95%CI, etc.)
Holló et al[97], 2012	Vitamin D3	13	Moderate (small sample, no control group)	40% seizure reduction after vitamin D3 supplementation	P = 0.04 (significant reduction in seizure frequency)
Mehvari et al[105], 2016	Vitamin E	65	Low (double-blind, placebo-controlled)	Improved seizure control and EEG findings	P < 0.001 (seizure frequency reduction), P = 0.001 (EEG improvement)
Elmazny et al[96], 2020	Vitamin D	42	Moderate (case-control design)	Lower vitamin D levels correlated with higher seizure frequency	P < 0.001 (vitamin D lower in epilepsy patients), P = 0.004 (seizure frequency correlation)
Nemati et al[59], 2021	Folate (Vitamin B9)	60	Moderate (cross-sectional, no intervention)	Association between low folate and epilepsy in children	Mean folate: 11.60 ± 6.89 nmol/L; correlation with neurodevelopmental delay
Kirik et al[73], 2021	Vitamin B12	26	High (retrospective, small sample)	Seizures in children resolved with vitamin B12 supplementation	No P values reported, high homocysteine levels noted
Portillo et al[75], 2023	Vitamin B12	1 (case report)	Not applicable	Seizures and psychosis improved with B12 supplementation	No statistical data
Specht et al[102], 2020	Vitamin D3 (Neonatal)	403 (cases), 1163 (controls)	Low (large sample, well-controlled)	High neonatal vitamin D levels correlated with increased epilepsy risk	HR adjust 1.86 (95%CI: 1.21-2.86), P trend = 0.004
Leandro-Merhi et al[85], 2023	Vitamin D	93	Moderate (cross-sectional, statistical correlation only)	Low vitamin D associated with worse seizure control in adults	P = 0.048 (seizure control linked to vitamin D levels)

¹This table summarizes the methodological quality and key findings of randomized controlled trials investigating the role of vitamin supplementation in epilepsy. While Vitamin D and Vitamin E showed potential benefits in seizure reduction, findings on Vitamin B12 and Folate are largely observational. Some studies exhibited a moderate-to-high risk of bias, highlighting the need for larger, well-controlled trials to confirm therapeutic efficacy.

EEG: Electroencephalogram; HR: Hazard ratio.