Consequences of Moderate Hyperhomocysteinemia in the Internal Medicine

Overview

Homocysteine is an intermediate product in the methionine metabolism, which is catalysed by several enzymes withB2, B6, B12 vitamins and folic acid as cofactors. Moderate hyperhomocysteinemia, defined as total homocysteineconcentration between 12 to 30 µmol/l, represents an independent risk factor for heart disease, vascular brain disease,phlebothrombosis and thromboembolic complications. It is related to placental abruptions, spina bifida and someneuropsychiatric disorders. Hyperhomocysteinemia is a metabolic syndrome based on interaction between geneticfactors (most frequently 677C/T polymorphism of methylentetrahydrofolate reductase), diseases and demographicfactors (smoking, aging, hormonal and nutritional factors). Moderate hyperhomocysteinemia occurs in about 20 to30 % of patients with clinical complications of atherosclerosis. Prospective and genetic studies have shown, thatmoderate hyperhomocysteinemia in healthy persons is only a weak predictor of cardiovascular diseases. Contraryto it, in patients with ischaemic heart disease, renal failure or diabetes mellitus and in thromboembolic disease,hyperhomocysteinemia represents a strong predictor of vascular morbidity and mortality. Toxic effects of hyperhomocysteinemiaon the vascular wall can be explained by a chemical modification of lipoproteins and vascularstructure, oxidative stress, endothelial dysfunction, inadequate endothelial cell regeneration, smooth muscle cellproliferation or by an accumulation of functionally non sufficient connective tissue. Also thrombogenic effects oran increased expression of cholesterol level controlling proteins and fatty acids in the liver can be considered.Treatment of hyperhomocysteinemia is based on the administration of pharmacological doses of folic acid, B6 andB12 vitamines, which can decrease total homocysteine concentration by 25 to 30 %. Such decrease, which is inaverage 3 µmol/l, results in the decrease of relative risk of ischaemic heart disease by 11 to 16 %, phlebothromboseby 25 % and vascular brain diseases by 19 to 24 %.

Key words:
homocysteine, hyperhomocysteinemia, risk of cardiovascular diseases, pharmoconutrition, B2, B6, B12vitamins, folic acid.