Homocysteine is a non-essential, thiol-containing amino acid which is produced from the intracellular de-methylation of dietary methionine . It is exported from the cells into the extracellular fluid at a slow but consistent rate and circulates in the blood mainly in an oxidised form, bound to plasma proteins. There are two major pathways for its further metabolism - trans-sulphuration to cysteine (by a vitamin B6-dependent pathway) or re-methylation to methionine (by a vitamin B12 and folic acid-dependent pathway). Vitamin B2 is also required for homocysteine metabolism on account of its role in the re-cycling and maintenance of folic acid levels. Excess homocysteine accumulates in the plasma when these pathways are not operating at optimum activity. While homocystinuria (homocystine in the urine with elevated plasma homocysteine levels) has been known since 1962, the pathological role of moderate hyper-homocysteinemia has only been generally recognised over the past decade .
Homocysteine is not a component of food or nutritional supplements, so the patient should not fast prior to the test but we do recommend avoiding B vitamin containing supplements for 24-48 hours. The blood sample should ideally be taken at midday, three to four hours after a protein-containing breakfast, so as to ensure an adequate methionine challenge (equivalent to about 0.5 gm of methionine).
The reference interval is less than 12.0 umol/L of plasma homocysteine, but the treatment goal varies (typically less than 7.0 umol/L of plasma homocysteine). An elevation of the plasma homocysteine by 5.0 umol/L has been associated with an increase of 1.7 in the odds ratio risk of cardiovascular disease (the same as an increase of 500 umol/l in plasma cholesterol .Men, on average, have a slightly higher plasma homocysteine level than women . This is thought to be associated with greater muscle mass, which increases the demand on the labile methyl pool for the synthesis of creatine.
Lavender (EDTA) tubes containing a special inhibitor (available from Biolab on request).