Nutritional and racial determinants of the increase in plasma homocysteine levels after methionine loading

Background: Low circulating plasma levels of total homocysteine (tHcy) are associated with a lower prevalence of coronary heart disease among black people than among white people living in Burkina Faso.Objective: The purpose of this study was to provide a rationale for a possible mechanism for the decrease in plasma tHcy levels among black people compared with white people living in Burkina Faso.Methods: Healthy, black, adult, lifelong inhabitants of Burkina Faso and healthy, white adults born in Italy but living in Burkina Faso ≥5 years were eligible for enrollment. Controlled diets were assigned to all subjects for 2 weeks before the study. After an overnight (12-hour) fast, a methionine-loading test was performed in all subjects. Plasma levels of tHcy, cysteine, glutathione, and cysteinylglycine were measured simultaneously using high-performance liquid chromatography after fasting (baseline) and at either 4 and 8 hours (n = 30) or 2, 4, 6, and 8 hours (n = 4) after methionine loading. During the 12 hours after loading, the clinical conditions and adverse events of subjects were monitored. Results were analyzed using the Student t test and Mann-Whitney U test.Results: Seventeen black adults (9 males, 8 females; median age, 21 years) and 17 white adults (8 males, 9 females; median age, 35 years) were enrolled. Mean plasma levels of tHcy, cysteine, and glutathione increased from mean baseline levels more slowly in the black group than in the white group and peaked 8 hours after methionine loading (16.8 ± 3.0 μmol/L, 130.4 ± 25.7 μmol/L, and 68.3 ± 21.2 μmol/L, respectively). In the white group, these levels peaked 4 hours after loading (16.1 ± 4.0 μmol/L, 215.8 ± 18.6 μmol/L, and 38.6 ± 12.4 μmol/L, respectively). Only the mean plasma cysteinylglycine level decreased significantly (from 35.7 ± 11.4 μmol/L to 19.0 ± 6.1 μmol/L; P < 0.01) in the black group after 4 hours. This decrease was followed by an increase after 8 hours (29.6 ± 12.0 μmol/L). In the white group, a less remarkable change in mean cysteinylglycine level was observed, with a peak after 4 hours (16.3 ± 4.3 μmol/L).Conclusions: The findings of this study suggest that, in addition to lower plasma tHcy levels, the metabolism of plasma tHcy is different in black people than in white people after methionine loading. This difference may be due to different alimentary habits associated with a reduced dietary availability of methionine. Moreover, the higher plasma levels of glutathione before and after methionine loading appear to occur exclusively in black people compared with whites and correspond with the variation of cysteinylglycine, suggesting that, in addition to nutritional factors, a racial component may contribute to the difference in plasma levels of tHcy. This difference also might explain, in part, the lower prevalence of coronary heart disease in black people living in Burkina Faso compared with that in other populations.