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Research Article: Human milk oligosaccharide composition following supplementation with folic acid vs (6S)-5-methyltetrahydrofolic acid during pregnancy and mediation by human milk folate forms

Date Published: 2023-12-06

Abstract:
Supplementation with folic acid versus (6S)-5-methyltetrahydrofolic acid (5-MTHF) results in different folate forms in human milk, with folic acid increasing unmetabolized folic acid (UMFA) at the expense of reduced folate forms. It is unknown whether folate forms present in human milk have further effects on human milk composition, such as human milk oligosaccharide (HMO) concentrations. We randomized 60 pregnant women in Canada to 0.6?mg/day folic acid or (6S)-5-MTHF. Human milk folate forms (LC-MS/MS) and nineteen HMOs (HPLC) were quantified at 1 week postpartum. Linear regression and causal mediation analysis were used to evaluate the effect of folate supplementation on HMO concentrations, and possible mediation by concentrations of UMFA and reduced folate forms in human milk (controlling for secretor status and parity). HMO concentrations were not different between groups, with no evidence of mediation by reduced folate forms; however, increased UMFA was associated with reduced concentrations of total HMOs and 3’-sialyllactose.

Introduction:
Human milk oligosaccharides (HMOs) are a group of complex carbohydrates that are highly abundant in human milk and play an important role in supporting infant health [1]. More than 150 different HMO structures have been identified and HMO composition can vary significantly between individuals and over the course of lactation [2]. This variation is driven by both fixed and modifiable factors, including maternal nutrition and supplementation [2, 3]. For example, multiple micronutrient supplementation has been…

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