Infant blood concentrations of folate markers and catabolites are modified by 5,10-methylenetetrahydrofolate reductase C677T genotype and dietary folate source.
- 2023-03
- The American journal of clinical nutrition 117(3)
- Rima Obeid
- Ines Warnke
- Anja Wittke
- Igor Bendik
- Barbara Troesch
- Rotraut Schoop
- Christina Hecht
- Johann Demmelmair
- Berthold Koletzko
- PubMed: 36872017
- DOI: 10.1016/j.ajcnut.2022.09.002
Study Design
- Type
- Randomized Controlled Trial (RCT)
- Sample size
- n = 182
- Population
- 110 breastfed infants (reference) and 182 infants who were randomly assigned to receive infant formulas enriched with either 78 μg folic acid or 81 μg (6S)-5-methyltetrahydrofolate (5-MTHF) per 100 g milk powder
- Methods
- Randomized assignment to receive infant formulas enriched with either 78 μg folic acid or 81 μg (6S)-5-methyltetrahydrofolate (5-MTHF) per 100 g milk powder for 12 wk; blood samples analyzed at ages <1 mo (baseline) and 16 wk
- Duration
- 12 wk
- Funding
- Unclear
- Large Human Trial
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 μg folic acid or 81 μg (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 = 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 ∼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. This trial was registered at clinicaltrials.gov as NCT02437721.Research Insights
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.
- Effect
- Beneficial
- Effect size
- Moderate
- Dose
- 78 μg per 100 g milk powder
infant formula with 5-MTHF (vs. folic acid) caused a significant increase in RBC folate concentration [1278 (466) vs. 947 (552), P < 0.001]
- Effect
- Beneficial
- Effect size
- Moderate
- Dose
- 78 μg per 100 g milk powder