The High Atherosclerotic Risk Among Epileptics: the Atheroprotective Role of Multivitamins

Abstract

Abstract. Neurologists have little concern about the high atherosclerotic risk among epileptics. Recent evidences mount that chronic epilepsy and prolonged use of antiepileptic drugs (AEDs) are associated with multiple risk factors that are critically implicated in pathobiology and dysfunction of the vessel wall through complex molecular mechanisms that promote atherogenesis. This review is concerned with three metabolic alterations, which are attributed as major risk factors for atherosclerosis among epileptics: altered metabolism of a) homocysteine (Hcy), b) lipids and lipoproteins, and c) uric acid. Most conventional AEDs reduce folic acid levels, thereby raising Hcy levels. Hyperhomosysteinemia is recently believed to induce endothelial dysfunction and promote atherosclerosis through complex oxidative and excitatory neurotoxic molecular mechanisms. However, Hcy itself is a convulsing substance with increased seizure recurrence and intractability to antiepileptic medications. AEDs can disturb lipid metabolism with resultant hypercholestrolemia and dyslipidemia, common recognized risks for atherosclerosis. Altered uric acid metabolism is common among epileptics. Uric acid has been implicated in endothelial cell damage and decreased endothelial nitric oxide bioavailability. In the presence of atherosclerotic milieu, uric acid interacts with other substrate toxicities and increased reactive oxygen species, accelerating atherosclerosis. The above information forms the rationale for future routine screening and correction of such metabolic alterations in epileptics. A convincing argument now develops that routine polyvitamin supplementation (folic acid, vitamin B12, vitamin B6, vitamin C, vitamin E, and β-carotene) becomes increasingly important for women and men receiving AEDs at all ages. The atheroprotective effect of multivitamins is through their antioxidant and anti-inflammatory effects together with their lipid and Hcy lowering effects.

Early Atherosclerotic Changes in the Patients with Idiopathic Epilepsy: Egyptian Preliminary Study

“…Epilepsy and prolonged antiepileptic drug treatment, particularly enzyme inducer AEDs have been found to induce hypercholesterolemia/dyslipidemia [12,13] and hyperuricemia [14]. It was found in this study that the level of HDL was significantly lower in the patients with epilepsy compared to the control group.…”

Homocysteine and Parkinson's disease: A dangerous liaison?

“…In the field of non-degenerative, neurological disorders, it is noteworthy that chronic epilepsy and prolonged use of antiepileptic drugs are associated with multiple risk factors for atherogenesis; in fact, most conventional antiepileptic drugs reduce folic acid levels, thereby raising homocysteine levels. Hyperhomocysteinemia has been suggested to induce endothelial dysfunction and promote atherosclerosis through complex oxidative and excitatory neurotoxic molecular mechanisms, but homocysteine itself is a convulsing substance and increased levels of the amino acid are associated with increased seizure recurrence and resistance to antiepileptic medications [70]. A negative correlation between homocysteine and folic acid concentrations was found in epileptic patients on therapy, without relation with the duration of treatment but neither with the seizure frequency, suggesting a more probable link with the anti-epileptic drug use rather than with the disease per se [71].…”

Nitric oxide synthase inhibition in rats: Melatonin reduces blood pressure and ischemia/reperfusion-induced infarct size

“…L-NAME (N v -Nitro-L-arginine methyl ester), L-NAME'/MEL (L-NAME'/Melatonin). The atheroprotective effect of multivitamins is through their antioxidant property were determined (24). Several pathological conditions such as hypertension increase production of ROS in the vascular wall (17).…”