Obeid Rima, Warnke Ines, Wittke Anja, Bendik Igor, Troesch Barbara, Schoop Rotraut, Hecht Christina, Demmelmair Johann, Koletzko Berthold
Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, Homburg/Saar, Germany.
DSM Nutritional Products Ltd., Kaiseraugst, Switzerland.
Am J Clin Nutr. 2023 Mar;117(3):509-517. doi: 10.1016/j.ajcnut.2022.09.002.
Folate intake and polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene may affect folate metabolism in infants.
We investigated the association between infant's MTHFR C677T genotype, the dietary folate source, and concentrations of folate markers in the blood.
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.
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.
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.
叶酸摄入量和亚甲基四氢叶酸还原酶（MTHFR）基因多态性可能影响婴儿的叶酸代谢。
我们研究了婴儿MTHFR C677T基因型、膳食叶酸来源与血液中叶酸标志物浓度之间的关联。
我们研究了110名母乳喂养的婴儿（对照组）和182名婴儿，这些婴儿被随机分配接受每100 g奶粉中添加78 μg叶酸或81 μg（6S）-5-甲基四氢叶酸（5-MTHF）的婴儿配方奶粉，持续12周。在小于1月龄（基线）和16周龄时采集血样。分析MTHFR基因型以及叶酸标志物和分解代谢产物[即对氨基苯甲酰谷氨酸（pABG）]的浓度。
在基线时，TT基因型携带者（与CC基因型相比）的红细胞（RBC）叶酸平均（标准差）浓度（均以nmol/L为单位）较低[1194（507）对1440（521），P = 0.033]，血浆pABG浓度也较低[5.7（4.9）对12.5（8.1），P < 0.001]，但血浆5-MTHF浓度较高[33.9（16.8）对24.0（12.6），P < 0.001]。无论基因型如何，含5-MTHF的婴儿配方奶粉（与叶酸相比）可使RBC叶酸浓度显著升高[1278（466）对947（552），P < 0.001]。在母乳喂养的婴儿中，从基线到16周，血浆5-MTHF和pABG浓度分别显著升高7.7（20.5）和6.4（10.5）。符合当前欧盟叶酸摄入量立法的婴儿配方奶粉在16周时使RBC叶酸和血浆pABG浓度升高（P < 0.001），高于配方奶喂养的婴儿。在16周时，所有喂养组中TT基因型携带者（与CC基因型相比）的血浆pABG浓度仍低约50%。
根据当前欧盟立法从婴儿配方奶粉中摄入叶酸比母乳喂养在更大程度上提高了婴儿的RBC叶酸和血浆pABG浓度，特别是在TT基因型携带者中。然而，这种摄入量并未完全消除pABG的基因型间差异。然而，这些差异是否具有任何临床相关性仍不清楚。该试验在clinicaltrials.gov上注册，注册号为NCT02437721。
