METHIONINE LOADING TEST IS NECESSARY FOR DETECTION OF HYPERHOMOCYSTEINEMIA

Hyperhomocysteinemia, defined as an elevated concentration of homocyst eine in the fasting state or after methionine loading, is an independe nt risk factor for premature atherosclerosis and venous thrombosis, Th e role of the methionine loading test (MLT) is, however, controversial . To determine the additional value of the MLT for diagnosis of hyperh omocysteinemia, we prospectively studied 281 patients with premature a rterial disease and 148 of their first-degree relatives in the outpati ent clinic of a general hospital, Total plasma homocysteine (fasting a nd 6 hours after methionine loading), folic acid, cobalamin, pyridoxin e, and creatinine concentrations were measured. Hyperhomocysteinemia w as defined as a fasting homocysteine concentration and/or an increase in homocysteine concentration after methionine loading exceeding the 9 5th percentile of a healthy control group, Hyperhomocysteinemia was fo und in 141 (33%) of the 429 subjects: 15% were diagnosed by fasting ho mocysteine concentration and 18% by MLT, Seventy-eight (55%) of the 14 1 hyperhomocysteinemic persons were diagnosed only by the MLT. Folic a cid was lower in the group with an elevated fasting homocysteine conce ntration than in those with only an abnormal MLT result (11 versus 15 nmol/L, p = 0.002). Folic acid was significantly negatively correlated , and creatinine significantly positively correlated, with both fastin g homocysteine concentration and increase in homocysteine concentratio n. Negative correlations of cobalamin and pyridoxine with fasting homo cysteine concentration were found. In conclusion, the MLT is necessary for diagnosis of hyperhomocysteinemia, because a considerable number of hyperhomocysteinemic persons (55%) remain undiagnosed with the dete rmination of a fasting homocysteine concentration alone.