Human milk unmetabolized folic acid is increased following supplementation with synthetic folic acid as compared to (6S)-5-methyltetrahydrofolic acid
Abstract Folic acid supplementation is recommended perinatally, but may increase unmetabolized folic acid (UMFA) in human milk; this is concerning as it is an inactive form which may be less bioavailable for the infant. “Natural” (6S)-5-methyltetrahydrofolic acid [(6S)-5-MTHF] is available as an alt...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-38224-4 |
| _version_ | 1797778957887602688 |
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| author | Kelsey M. Cochrane Rajavel Elango Angela M. Devlin Jennifer A. Hutcheon Crystal D. Karakochuk |
| author_facet | Kelsey M. Cochrane Rajavel Elango Angela M. Devlin Jennifer A. Hutcheon Crystal D. Karakochuk |
| author_sort | Kelsey M. Cochrane |
| collection | DOAJ |
| description | Abstract Folic acid supplementation is recommended perinatally, but may increase unmetabolized folic acid (UMFA) in human milk; this is concerning as it is an inactive form which may be less bioavailable for the infant. “Natural” (6S)-5-methyltetrahydrofolic acid [(6S)-5-MTHF] is available as an alternative to folic acid, and may prevent the accumulation of UMFA in human milk. Pregnant women (n = 60) were enrolled at 8–21 weeks of gestation and randomized to 0.6 mg/day folic acid or (6S)-5-MTHF. At ~ 1-week postpartum, participants provided a human milk specimen. Total human milk folate (nmol/L) and concentrations of UMFA (nmol/L) were quantified via LC–MS/MS. Differences between groups were evaluated using multivariable quantile/linear regression, adjusting for dietary folate, weeks supplementing, and milk collection methods. No significant difference in total milk folate was found; however, the median milk UMFA concentration was 11 nmol/L higher in those receiving folic acid versus (6S)-5-MTHF (95% CI = 6.4–17 nmol/L), with UMFA representing 28% and 2% of total milk folate. In conclusion, the form of supplemental folate had markedly differential effects on the human milk folate profile, with folic acid increasing the mean proportion of milk UMFA by ~ 14-fold. Investigation of whether increased UMFA impacts folate-related metabolism and infant health outcomes is required. |
| first_indexed | 2024-03-12T23:24:03Z |
| format | Article |
| id | doaj.art-361cc5c370454cf9a33bc0ab4ed46d0a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T23:24:03Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-361cc5c370454cf9a33bc0ab4ed46d0a2023-07-16T11:13:48ZengNature PortfolioScientific Reports2045-23222023-07-011311910.1038/s41598-023-38224-4Human milk unmetabolized folic acid is increased following supplementation with synthetic folic acid as compared to (6S)-5-methyltetrahydrofolic acidKelsey M. Cochrane0Rajavel Elango1Angela M. Devlin2Jennifer A. Hutcheon3Crystal D. Karakochuk4Food, Nutrition and Health, Faculty of Land and Food Systems, The University of British ColumbiaBC Children’s Hospital Research Institute, Healthy StartsBC Children’s Hospital Research Institute, Healthy StartsBC Children’s Hospital Research Institute, Healthy StartsFood, Nutrition and Health, Faculty of Land and Food Systems, The University of British ColumbiaAbstract Folic acid supplementation is recommended perinatally, but may increase unmetabolized folic acid (UMFA) in human milk; this is concerning as it is an inactive form which may be less bioavailable for the infant. “Natural” (6S)-5-methyltetrahydrofolic acid [(6S)-5-MTHF] is available as an alternative to folic acid, and may prevent the accumulation of UMFA in human milk. Pregnant women (n = 60) were enrolled at 8–21 weeks of gestation and randomized to 0.6 mg/day folic acid or (6S)-5-MTHF. At ~ 1-week postpartum, participants provided a human milk specimen. Total human milk folate (nmol/L) and concentrations of UMFA (nmol/L) were quantified via LC–MS/MS. Differences between groups were evaluated using multivariable quantile/linear regression, adjusting for dietary folate, weeks supplementing, and milk collection methods. No significant difference in total milk folate was found; however, the median milk UMFA concentration was 11 nmol/L higher in those receiving folic acid versus (6S)-5-MTHF (95% CI = 6.4–17 nmol/L), with UMFA representing 28% and 2% of total milk folate. In conclusion, the form of supplemental folate had markedly differential effects on the human milk folate profile, with folic acid increasing the mean proportion of milk UMFA by ~ 14-fold. Investigation of whether increased UMFA impacts folate-related metabolism and infant health outcomes is required.https://doi.org/10.1038/s41598-023-38224-4 |
| spellingShingle | Kelsey M. Cochrane Rajavel Elango Angela M. Devlin Jennifer A. Hutcheon Crystal D. Karakochuk Human milk unmetabolized folic acid is increased following supplementation with synthetic folic acid as compared to (6S)-5-methyltetrahydrofolic acid Scientific Reports |
| title | Human milk unmetabolized folic acid is increased following supplementation with synthetic folic acid as compared to (6S)-5-methyltetrahydrofolic acid |
| title_full | Human milk unmetabolized folic acid is increased following supplementation with synthetic folic acid as compared to (6S)-5-methyltetrahydrofolic acid |
| title_fullStr | Human milk unmetabolized folic acid is increased following supplementation with synthetic folic acid as compared to (6S)-5-methyltetrahydrofolic acid |
| title_full_unstemmed | Human milk unmetabolized folic acid is increased following supplementation with synthetic folic acid as compared to (6S)-5-methyltetrahydrofolic acid |
| title_short | Human milk unmetabolized folic acid is increased following supplementation with synthetic folic acid as compared to (6S)-5-methyltetrahydrofolic acid |
| title_sort | human milk unmetabolized folic acid is increased following supplementation with synthetic folic acid as compared to 6s 5 methyltetrahydrofolic acid |
| url | https://doi.org/10.1038/s41598-023-38224-4 |
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