Infant blood concentrations of folate markers and catabolites are modified by 5,10-methylenetetrahydrofolate reductase C677T genotype and dietary folate source

Background: Folate intake and polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene may affect folate metabolism in infants. Objectives: We investigated the association between infant's MTHFR C677T genotype, the dietary folate source, and concentrations of folate markers in the blood. Methods: We studied 110 breastfed infants (reference) and 182 infants who were randomly assigned to receive infant formulas enriched with either 78 mu g folic acid or 81 mu g (6S)-5-methyltetrahydrofolate (5-MTHF) per 100 g milk powder for 12 wk. The blood samples were available at the ages of <1 mo (baseline) and 16 wk. MTHFR genotype and concentrations of folate markers and catabolites [i.e., para-aminobenzoylglutamate (pABG)] were analyzed. Results: At baseline, carriers of the TT genotype (vs. CC) had lower mean (SD) concentrations (all in nmol/L) of red blood cell (RBC) folate [1194 (507) vs. 1440 (521), P 1/4 0.033) and plasma pABG [5.7 (4.9) vs. 12.5 (8.1), P < 0.001] but higher plasma 5-MTHF [33.9 (16.8) vs. 24.0 (12.6), P < 0.001]. Irrespective of the genotype, infant formula with 5-MTHF (vs. folic acid) caused a significant increase in RBC folate concentration [1278 (466) vs. 947 (552), P < 0.001]. In breastfed infants, plasma concentrations of 5-MTHF and pABG increased significantly by 7.7 (20.5) and 6.4 (10.5), respectively, from baseline to 16 wk. Infant formula that complies with the present EU legislation for folate intake increased RBC folate and plasma pABG concentrations at 16 wk (P < 0.001) than formula-fed infants. At 16 wk, plasma pABG concentrations remained similar to 50% lower in carriers of the TT (vs. the CC) genotype among all feeding groups. Conclusions: Folate intake from infant formula according to the present EU legislation increased RBC folate and plasma pABG concentrations in infants to a greater extent than breastfeeding, particularly in carriers of the TT genotype. However, this intake did not completely abolish the between-genotype differences in pABG. Whether these differences have any clinical relevance, however, remains unclear.

Automated summary

This study investigated the association between infant's MTHFR C677T genotype, the dietary folate source, and concentrations of folate markers in the blood. The results showed that the use of infant formula with 5-MTHF increased the concentrations of RBC folate and plasma pABG in infants. Over time, the plasma concentrations of 5-MTHF and pABG also significantly increased in breastfed infants. However, carriers of the TT genotype still had lower pABG concentrations compared to carriers of the CC genotype, and it is unclear whether these differences have any clinical relevance.