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Abuknesha, Nada R. (2024) Plasma fatty acids and antioxidant vitamins of patients with drug-resistant epilepsy aged 5-18 year from the Khartoum province, Sudan: implications for seizure frequency? Doctoral thesis, London Metropolitan University.
Thirty percent of patients with epilepsy do not respond to anti-epileptic drug treatment (AEDs) and continue to endure uncontrollable seizures. They are known to have drug-resistant epilepsy (DRE). Neurosurgery and the ketogenic diet offer patients hopeful measures to control their seizures, however are associated with unacceptable health risks. This demonstrates an unmet need for safer treatment options to be considered. The effect of supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFAs): eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, on plasma fatty acid profiles and fat-soluble antioxidant vitamin concentrations in 83 patients with DRE receiving AEDs (11.2 [SD, 7.2] years; 25F/58M) was investigated in a double-blind, placebo-controlled, randomized clinical trial. Patients were screened for eligibility at baseline and randomly assigned to receive 12-months of supplementation with high DHA (417.8mg DHA & 50.8mg EPA), high EPA (81.2mg DHA & 385.6mg EPA) or placebo (high oleic sunflower seed oil). Patients or their carers were given a diary to document the occurrence of seizures. 58 patients completed the intervention: high DHA; n=18, high EPA; n=21, and placebo (oleic acid) group; n=19. Plasma levels ofn-3 PUFAs, α-tocopherol and β-carotene were analysed using gas-liquid and high-performance liquid chromatography, respectively, and measured at both baseline and month 12. Statistical analyses were conducted using IBM SPSS Statistics 25 and parametric-based testing.
In comparison to their healthy counterparts (8.3 [SD, 2.7] years; 13F/18M), there were 75 and 66% significantly lower levels of EPA (0.05±0.06% vs. 0.2±0.08%; p<0.005), DHA (0.4±0.23% vs. 1.16±0.41 %; p<0.005), and 55 and 79% lower concentrations of α-tocopherol (5.91±3.28µmol/L vs. 13.3±2.46µmol/L; p<0.005) and β-carotene (0.06±0.07µmol/L vs. 0.28±0.13µmol/L; p<0.005), respectively in patients at baseline. Vitamin concentrations were below the cut-off level of deficiency, suggesting free-radical overload in patients. Significant negative correlations between EPA (r= -0.23; p<0.05), DHA (r== -0.23; p<0.05), and seizure frequency were detected among all patients. At month 12 patients treated with high EPA and high DHA demonstrated significant increases in EPA (89 and 61.2%), DHA (55 and 59%), α-tocopherol (54 and 55%) and β-carotene (77 and 80%) compared to the placebo (oleic acid) group. Negative correlations were found between EPA, DHA, α-tocopherol, β-carotene and seizure frequency in the high EPA and DHA groups, respectively. However, these associations did not reach a level of statistical significance most likely due to the small sample size. Regardless, the findings are in line with the seizure reduction effect of39% (high DHA) and 42% (high EPA) at month 12 compared to baseline in patients (Ibrahim et al, 2018).
The significant negative correlations of EPA and DHA with baseline seizure frequency support the hypothesis that n-3 deficiency may have implications for seizure frequency in DRE. Supplementation with high EPA or high DHA may correct this deficiency and concurrently mitigate the concentrations of antioxidant vitamins in DRE, which may have had implications for seizure control in the patients. Therefore, the seizure amelioration effect reported in previous studies is likely due to the correction of the deficiency of these nutrients. This thesis documents the efficacy and the safety of long duration n-3 EPA and DHA supplementation as adjunctive therapy for the management of uncontrollable seizures inDRE.
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