Homocysteine (Hcy) is a thiol‐containing amino acid produced by the intracellular demethylation of methionine. Total homocysteine (tHcy) represents the sum of all forms of Hcy including forms of oxidized, protein‐bound and free.
Elevated levels of tHcy has emerged as an important risk factor in the assessment of cardiovascular disease. Excess Hcy in the blood stream may cause injuries to arterial vessels due to its irritant nature, and result in inflammation and plaque formation, which may eventually cause blockage of blood flow to the heart.
Elevated tHcy levels are caused by four major factors, including:
1. genetic deficiencies in enzymes involved in Hcy metabolism such as cystathionine beta‐synthase (CBS), methionine synthase (MS), and methylenetetrahydrofolate reductase (MTHFR);
2. nutritional deficiency in B vitamins such as B6, B12 and folate;
3. renal failure for effective amino acid clearance; and
4. drug interactions, such as with nitric oxide, methotrexate and phenytoin that interfere with Hcy metabolism.
Elevated levels of tHcy are also linked with Alzheimer’s disease, neuropsychiatric diseases and Osteoporosis. Guidelines for tHcy determination in clinical laboratories have been established.