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

## TL;DR

This study found that folic acid supplementation during pregnancy increases unmetabolized folic acid in breast milk, which may reduce certain milk sugars.

## Contribution

The study is the first to link folate supplementation type to human milk oligosaccharide concentrations via milk folate forms.

## Key findings

- HMO concentrations were not different between folic acid and 5-MTHF groups.
- Increased unmetabolized folic acid was associated with reduced total HMOs and 3’-sialyllactose.
- Reduced folate forms did not mediate the effect on HMO concentrations.

## 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.