Methionine loading test is necessary for detection of hyperhomocysteinemia

Hyperhomocysteinemia, defined as an elevated concentration of homocysteine in the fasting state or after methionine loading, is an independent risk factor for premature atherosclerosis and venous thrombosis. The role of the methionine loading test (MLT) is, however, controversial. To determine the additional value of the MLT for diagnosis of hyperhomocysteinemia, we prospectively studied 281 patients with premature arterial disease and 148 of their first-degree relatives in the outpatient clinic of a general hospital. Total plasma homocysteine (fasting and 6 hours after methionine loading), folic acid, cobalamin, pyridoxine, and creatinine concentrations were measured. Hyperhomocysteinemia was defined as a fasting homocysteine concentration and/or an increase in homocysteine concentration after methionine loading exceeding the 95th percentile of a healthy control group. Hyperhomocysteinemia was found in 141 (33%) of the 429 subjects: 15% were diagnosed by fasting homocysteine concentration and 18% by MLT. Seventy-eight (55%) of the 141 hyperhomocysteinemic persons were diagnosed only by the MLT. Folic acid was lower in the group with an elevated fasting homocysteine concentration 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 fasting homocysteine concentration and increase in homocysteine concentration. Negative correlations of cobalamin and pyridoxine with fasting homocysteine 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 determination of a fasting homocysteine concentration alone.