L N Ranganathan1, S Ramaratnam. 1. Institute of Neurology, Madras Medical College, 18 Appa Kannu Lane, 1st floor, "Garuda Sailam", Royapetta, Chennai, Tamil Nadu, India, 600014. ln1@vsnl.com
Abstract
BACKGROUND: Vitamins have been reported to be effective in controlling certain types of seizures and to prevent some of the harmful effects of antiepileptic drugs (AEDs). In this review we will summarize evidence from randomized controlled trials. OBJECTIVES: To assess if vitamins improve seizure control, reduce adverse effects of AEDs or improve the quality of life in people with epilepsy. SEARCH STRATEGY: We searched MEDLINE from 1966 to 2004, the Cochrane Epilepsy Group trials register (December 2004), CENTRAL (the Cochrane Controlled Trials Register) (TheCochraneLibrary Issue 4, 2004), and cross-references from identified studies. SELECTION CRITERIA: Randomized or quasi-randomized studies investigating the effects of one or more vitamins given alone or in addition to AEDs to people of any age with any type of epilepsy. DATA COLLECTION AND ANALYSIS: Both reviewers assessed the trials for inclusion and extracted the data. Outcomes assessed included seizure frequency, gingival hyperplasia, neuropathy, changes in bone mineral content, serum calcium, alkaline phosphatase, hemogram, serum levels of AEDs, neuropsychological and quality of life outcomes. Primary analyses were by intention to treat. MAIN RESULTS: Fifteen studies met our inclusion criteria and were of poor methodological quality. None described randomization methods and most enrolled small numbers of participants. Nine studies (331 participants) investigated folic acid. Two studies (75 participants) found no effect for the outcome 50% or greater reduction in seizure frequency (OR 0.96; 95% CI 0.32 to 2.29). Also, no evidence was found for an effect on gingival health, intelligence, behavior, mental health or personality, or measures of red blood volume and hemoglobin content. Folic acid was not associated with any consistent changes in serum phenytoin or phenobarbitone levels or improvement in the mean motor conduction velocities of peripheral nerves. One small study (72 participants) found that thiamine improves neuropsychological functions related to psychomotor speed, visuospatial abilities, selective attention and verbal abstracting ability. One study (226 participants) found a significantly higher bone mineral content (BMC) among patients with epilepsy taking AEDs with vitamin D supplementation compared to controls who were not given supplementation (OR 3.6; 95% CI 2.48 to 4.72; p < 0.00001). The studies found no significant effects on serum calcium, alkaline phosphatase or general well-being. One small study (24 participants) found a significant decrease in seizure frequency in those treated with vitamin E compared to placebo (p = 0.00005; Peto OR 26.73; 95% CI 5.46 to 130.92). AUTHORS' CONCLUSIONS: In view of methodological deficiencies and limited number of individual studies, we have found no reliable evidence to support the routine use of vitamins in patients with epilepsy. Further trials are needed, especially to assess the utility of vitamin D supplementation to prevent osteomalacia and the role of vitamin E on seizures and thiamine in improving cognitive functions.
BACKGROUND: Vitamins have been reported to be effective in controlling certain types of seizures and to prevent some of the harmful effects of antiepileptic drugs (AEDs). In this review we will summarize evidence from randomized controlled trials. OBJECTIVES: To assess if vitamins improve seizure control, reduce adverse effects of AEDs or improve the quality of life in people with epilepsy. SEARCH STRATEGY: We searched MEDLINE from 1966 to 2004, the Cochrane Epilepsy Group trials register (December 2004), CENTRAL (the Cochrane Controlled Trials Register) (TheCochraneLibrary Issue 4, 2004), and cross-references from identified studies. SELECTION CRITERIA: Randomized or quasi-randomized studies investigating the effects of one or more vitamins given alone or in addition to AEDs to people of any age with any type of epilepsy. DATA COLLECTION AND ANALYSIS: Both reviewers assessed the trials for inclusion and extracted the data. Outcomes assessed included seizure frequency, gingival hyperplasia, neuropathy, changes in bone mineral content, serum calcium, alkaline phosphatase, hemogram, serum levels of AEDs, neuropsychological and quality of life outcomes. Primary analyses were by intention to treat. MAIN RESULTS: Fifteen studies met our inclusion criteria and were of poor methodological quality. None described randomization methods and most enrolled small numbers of participants. Nine studies (331 participants) investigated folic acid. Two studies (75 participants) found no effect for the outcome 50% or greater reduction in seizure frequency (OR 0.96; 95% CI 0.32 to 2.29). Also, no evidence was found for an effect on gingival health, intelligence, behavior, mental health or personality, or measures of red blood volume and hemoglobin content. Folic acid was not associated with any consistent changes in serum phenytoin or phenobarbitone levels or improvement in the mean motor conduction velocities of peripheral nerves. One small study (72 participants) found that thiamine improves neuropsychological functions related to psychomotor speed, visuospatial abilities, selective attention and verbal abstracting ability. One study (226 participants) found a significantly higher bone mineral content (BMC) among patients with epilepsy taking AEDs with vitamin D supplementation compared to controls who were not given supplementation (OR 3.6; 95% CI 2.48 to 4.72; p < 0.00001). The studies found no significant effects on serum calcium, alkaline phosphatase or general well-being. One small study (24 participants) found a significant decrease in seizure frequency in those treated with vitamin E compared to placebo (p = 0.00005; Peto OR 26.73; 95% CI 5.46 to 130.92). AUTHORS' CONCLUSIONS: In view of methodological deficiencies and limited number of individual studies, we have found no reliable evidence to support the routine use of vitamins in patients with epilepsy. Further trials are needed, especially to assess the utility of vitamin D supplementation to prevent osteomalacia and the role of vitamin E on seizures and thiamine in improving cognitive functions.