DETERMINANTS AND VITAMIN RESPONSIVENESS OF INTERMEDIATE HYPERHOMOCYSTEINEMIA (LESS-THAN-OR-EQUAL-TO 40 MU-MOL LITER) - THE HORDALAND HOMOCYSTEINE STUDY/

From 1992-93, we screened 18,043 subjects, aged 40-67 yr, and found 67 cases (0.4%) with total plasma homocysteine (tHcy) greater than or eq ual to 40 mu mol/liter. Compared to 329 controls, the cases had lower plasma folate and cobalamin levels, lower intake of vitamin supplement s, consumed more coffee, and were more frequently smokers, Homozygosit y for the C677T mutation in the methylenetetrahydrofolate reductase ge ne was observed in 73.1% of the cases and 10.2% of the controls, Only seven cases with cobalamin deficiency and one with homocystinuria rece ived specific therapeutic instructions. 2 yr after the screening, 58 s ubjects were reinvestigated. 41 still had tHcy > 20 mu mol/liter, and in 37 of these, intervention with low dose folic acid (0.2 mg/d) was s tarted. Notably, 34 of 37 (92%) had homozygosity for the C677T mutatio n, Plasma tHcy was reduced in all but two after 7 wk, and became norma l within 7 mo in 21 of 37 subjects, Most of the remaining subjects obt ained a normal tHcy level with 5 mg/d of folic acid, We conclude that most subjects with hyperhomocysteinemia greater than or equal to 40 mu mol/liter in the general population have the C677T mutation combined with low folate status, Daily supplement of low dose folic acid will r educe and often normalize their tHcy level.