Serum homocysteine and folate concentrations among a US cohort of adolescents before and after folic acid fortification

Abstract

Objective: We assessed serum homocysteine (tHcy) and folate concentrations among US adolescents before and after fortification of cereal-grain products with folic acid, and associations with demographic, behavioural and physiological factors.

Design: Observational study conducted among participants of a randomized trial.

Setting: The Child and Adolescent Trial for Cardiovascular Health (CATCH) study.

Subjects: Adolescents (n 2445) in grades 8 (pre-fortification, mean age 14 years) and 12 (post-fortification, mean age 18 years).

Results: Average serum concentrations of tHcy, folate and vitamin B6 increased by 17 %, 16 % and 14 %, respectively, while serum concentrations of vitamin B12 decreased by 11 % post-fortification. Folic acid fortification provided, on average, an additional intake of 118 μg folate/d. Male sex (P < 0.0001) and white race (P = 0.0008) were associated with significantly greater increases in tHcy concentration, while increases in BMI (P = 0.006) and serum folate concentration (P < 0.0001) were associated with significant decreases in tHcy concentration. Female sex (P < 0.0001), non-smoking (P < 0.0001), use of multivitamins (P < 0.0001) and higher dietary intake of folate (P = 0.001) were associated with significantly greater increases in serum folate concentrations. From grade 8 to grade 12, the upward age trend in serum tHcy concentration was uninterrupted in its course (P > 0.50); whereas serum folic acid concentration showed a downward trend that incurred a discrete jump upward (17 % higher; P < 0.0001) with fortification. These trends differed significantly for males v. females (P < 0.001 for interaction).

Conclusions: Fortification had a significant impact on improving folate status but not serum tHcy concentrations among US adolescents.

Figure 1

Inverse relation between serum homocysteine (tHcy) and serum folate concentrations in the CATCH cohort before and after national folic acid fortification. From Grade 8 (red, pre-fortification) to Grade 12 (black, post-fortification) the breakpoint of the fitted segmented regression curve shifted rightward, indicating higher folate levels, while the entire curve shifted upward, indicating higher homocysteine levels for a given folate level. Segmented regression curves were fitted to 3,152 available joint measurements of homocysteine and folate concentrations, excluding users of multivitamins or supplements. Symbols represent a 5% random sample of the fitted data.

Figure 2

Trends in serum homocysteine and serum folate concentration in the CATCH cohort, before and after national folate fortification. Upper panel: For both males (black) and females (red), the increase in homocysteine levels from Grade 8 to Grade 12 was a continuation of the within-grade age trend. Lower panel: For both males (black) and females (red), post-fortification folate levels (Grade 12) were significantly higher than would be predicted by continuation of the within-grade age trend at Grade 8 (p<0.0001 for discontinuity between grades). Regression lines were fitted to 4620 measurements for the combined grades, excluding users of multivitamins or supplements. Symbols represent a 5% random sample of the fitted data. For both homocysteine (upper panel) and folate (lower panel), the age trend was significantly steeper for males than females (p<0.0001 for age × sex interaction).