Analytic Approaches for the Treatment of Hyperhomocysteinemia and Its Impact on Vascular Disease

• Published in: Cardiovascular drugs and therapy 2018-04, Vol.32 (2), p.233-240
• Main Authors: Kang, Soo-Sang, Rosenson, Robert S.
• Format: Article
• Language: English
• Subjects: Animals; Arteriosclerosis; Atherosclerosis; Betaine; Betaine - adverse effects; Betaine - therapeutic use; Biomarkers - blood; Cardiology; Cardiovascular Diseases - diagnosis; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - prevention & control; Cholesterol; Depletion; Folic acid; Folic Acid - adverse effects; Folic Acid - therapeutic use; Genetic Predisposition to Disease; Genetics; Health risk assessment; Homocysteine; Homocysteine - blood; Humans; Hyperhomocysteinemia; Hyperhomocysteinemia - diagnosis; Hyperhomocysteinemia - drug therapy; Hyperhomocysteinemia - epidemiology; Hyperhomocysteinemia - genetics; Medicine; Medicine & Public Health; Metabolism; Methionine; Phenotype; Review Article; Reviews; Risk analysis; Risk Factors; Tetrahydrofolates - adverse effects; Tetrahydrofolates - therapeutic use; Treatment Outcome; Vascular diseases; Vitamin B
• ISSN: 0920-3206; 1573-7241
• DOI: 10.1007/s10557-018-6790-1

Homocysteine is an intermediary metabolite in the methionine cycle. Accumulation of homocysteine is caused either by mutation of relevant genes or by nutritional depletion of related vitamin(s). This review covers the historical background of hyperhomocysteinemia in which indispensable subjects in relation to underlying pathophysiological processes are discussed with the view of metabolism and genetics of folate and methionine cycles. This review emphasizes the unique role of homocysteine that is clearly distinct from other risk factors, particularly cholesterol in the development of vascular disease. The critical issue in understanding the role of homocysteine is the relation with plasma folic acid. The majority of subjects with homocysteine > 15 μmol/L exhibit plasma folate  15 μmol/L demonstrated a higher prevalence of vascular disease. Analytic approaches to treat hyperhomocysteinemia are discussed in which stepwise administration with nutritional doses of folic acid, 5-methyitetrahydrofolate (5-MTHF), and betaine is provided singly or by combined manner based on clinical and laboratory evaluations. Whether correction of hyperhomocysteinemia is able to prevent the development of homocysteine-associated vascular disease remains an unresolved issue. The review discussed a biochemical and mechanistic approach to resolve questions involved in the relation between homocysteine and the development of atherosclerotic vascular disease.