Postmethionine-load homocysteine determination for the diagnosis hyperhomocysteinaemia and efficacy of homocysteine lowering treatment regimens

Abstract

Substantial epidemiological evidence supports the vision that moderate hyperhomocysteinaemia is a graded and independent cardiovascular risk factor. The additional value of the methionine loading test for the assessment of hyperhomocysteinaemia continues to be disputed. This overview presents the historical background for the rationale of the methionine loading test and describes determinants and variability of the postmethionine-load homocysteine concentration. The association of postmethionine-load homocysteine concentrations and the risk of cardiovascular events is discussed. Furthermore, the results of homocysteine lowering treatment on postmethionine-load homocysteine are given. Up to 50% of subjects with hyperhomocysteinaemia can only be detected after performing a methionine loading test; these subjects have a normal fasting homocysteine. Both fasting and postmethionine-load homocysteine concentrations are influenced by serum folate and creatinine concentrations and by the methylenetetrahydrofolate reductase genotype, and may be subject to a wide intra-individual variability (approximately 20%). Cross-sectional studies suggest that cardiovascular risk may increase gradually from postmethionine-load homocysteine concentrations above 38 micromol/l. Supplementation with folic acid 0.5 mg daily adequately reduces postmethionine-load homocysteine; addition of pyridoxine appears to have no further homocysteine lowering effect. Prospective studies supporting the clinical significance of the methionine loading test for individual patient counselling are lacking; it seems, therefore, prudent to restrict this test for research purposes.