Supplementation with (6S)-5-methyltetrahydrofolic acid appears as effective as folic acid in maintaining maternal folate status while reducing unmetabolised folic acid in maternal plasma: a randomised trial of pregnant women in Canada
Folic acid supplementation is recommended during pregnancy to support healthy fetal development; (6S)-5-methyltetrahydrofolic acid ((6S)-5-MTHF) is available in some commercial prenatal vitamins as an alternative to folic acid, but its effect on blood folate status during pregnancy is unknown. To ad...
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Veröffentlicht in: | British journal of nutrition 2024-01, Vol.131 (1), p.92-102 |
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description | Folic acid supplementation is recommended during pregnancy to support healthy fetal development; (6S)-5-methyltetrahydrofolic acid ((6S)-5-MTHF) is available in some commercial prenatal vitamins as an alternative to folic acid, but its effect on blood folate status during pregnancy is unknown. To address this, we randomised sixty pregnant individuals at 8–21 weeks’ gestation to 0·6 mg/d folic acid or (6S)-5-MTHF × 16 weeks. Fasting blood specimens were collected at baseline and after 16 weeks (endline). Erythrocyte and serum folate were quantified via microbiological assay (as globally recommended) and plasma unmetabolised folic acid (UMFA) via LC-MS/MS. Differences in biochemical folate markers between groups were explored using multivariable linear/quantile regression, adjusting for baseline concentrations, dietary folate intake and gestational weeks. At endline (n 54), the mean values and standard deviations (or median, inter-quartile range) of erythrocyte folate, serum folate and plasma UMFA (nmol/l) in those supplemented with (6S)-5-MTHF v. folic acid, respectively, were 1826 (sd 471) and 1998 (sd 421); 70 (sd 13) and 78 (sd 17); 0·5 (0·4, 0·8) and 1·3 (0·9, 2·1). In regression analyses, erythrocyte and serum folate did not differ by treatment group; however, concentrations of plasma UMFA in pregnancy were 0·6 nmol/l higher (95 % CI 0·2, 1·1) in those supplementing with folic acid as compared with (6S)-5-MTHF. In conclusion, supplementation with (6S)-5-MTHF may reduce plasma UMFA by ∼50 % as compared with supplementation with folic acid, the biological relevance of which is unclear. As folate is currently available for purchase in both forms, the impact of circulating maternal UMFA on perinatal outcomes needs to be determined. |
doi_str_mv | 10.1017/S0007114523001733 |
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To address this, we randomised sixty pregnant individuals at 8–21 weeks’ gestation to 0·6 mg/d folic acid or (6S)-5-MTHF × 16 weeks. Fasting blood specimens were collected at baseline and after 16 weeks (endline). Erythrocyte and serum folate were quantified via microbiological assay (as globally recommended) and plasma unmetabolised folic acid (UMFA) via LC-MS/MS. Differences in biochemical folate markers between groups were explored using multivariable linear/quantile regression, adjusting for baseline concentrations, dietary folate intake and gestational weeks. At endline (n 54), the mean values and standard deviations (or median, inter-quartile range) of erythrocyte folate, serum folate and plasma UMFA (nmol/l) in those supplemented with (6S)-5-MTHF v. folic acid, respectively, were 1826 (sd 471) and 1998 (sd 421); 70 (sd 13) and 78 (sd 17); 0·5 (0·4, 0·8) and 1·3 (0·9, 2·1). In regression analyses, erythrocyte and serum folate did not differ by treatment group; however, concentrations of plasma UMFA in pregnancy were 0·6 nmol/l higher (95 % CI 0·2, 1·1) in those supplementing with folic acid as compared with (6S)-5-MTHF. In conclusion, supplementation with (6S)-5-MTHF may reduce plasma UMFA by ∼50 % as compared with supplementation with folic acid, the biological relevance of which is unclear. As folate is currently available for purchase in both forms, the impact of circulating maternal UMFA on perinatal outcomes needs to be determined.</description><identifier>ISSN: 0007-1145</identifier><identifier>EISSN: 1475-2662</identifier><identifier>DOI: 10.1017/S0007114523001733</identifier><identifier>PMID: 37649241</identifier><language>eng</language><publisher>Cambridge, UK: Cambridge University Press</publisher><subject>Acids ; Blood ; Canada ; Chromatography, Liquid ; Dietary intake ; Dietary Supplements ; Dihydrofolate reductase ; Erythrocytes ; Female ; Fetuses ; Folic Acid ; Food fortification ; Human and Clinical Nutrition ; Humans ; Informed consent ; Metabolism ; Microbiological assaying ; Physiology ; Plasma ; Pregnancy ; Pregnant Women ; Public health ; Regression analysis ; Supplements ; Tandem Mass Spectrometry ; Vitamin B ; Vitamins ; Womens health</subject><ispartof>British journal of nutrition, 2024-01, Vol.131 (1), p.92-102</ispartof><rights>Crown Copyright - The University of British Columbia, 2023. Published by Cambridge University Press on behalf of The Nutrition Society</rights><rights>Crown Copyright - The University of British Columbia, 2023. Published by Cambridge University Press on behalf of The Nutrition Society. This work is licensed under the Creative Commons Attribution License This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited. (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-f1efc81624de4f26efe05eafd2460a0bdecb592729833608b9b17536d2b895d43</citedby><cites>FETCH-LOGICAL-c416t-f1efc81624de4f26efe05eafd2460a0bdecb592729833608b9b17536d2b895d43</cites><orcidid>0000-0001-5628-2850</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.cambridge.org/core/product/identifier/S0007114523001733/type/journal_article$$EHTML$$P50$$Gcambridge$$Hfree_for_read</linktohtml><link.rule.ids>164,314,780,784,27924,27925,55628</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37649241$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cochrane, Kelsey M.</creatorcontrib><creatorcontrib>Elango, Rajavel</creatorcontrib><creatorcontrib>Devlin, Angela M.</creatorcontrib><creatorcontrib>Mayer, Chantal</creatorcontrib><creatorcontrib>Hutcheon, Jennifer A.</creatorcontrib><creatorcontrib>Karakochuk, Crystal D.</creatorcontrib><title>Supplementation with (6S)-5-methyltetrahydrofolic acid appears as effective as folic acid in maintaining maternal folate status while reducing unmetabolised folic acid in maternal plasma: a randomised trial of pregnant women in Canada</title><title>British journal of nutrition</title><addtitle>Br J Nutr</addtitle><description>Folic acid supplementation is recommended during pregnancy to support healthy fetal development; (6S)-5-methyltetrahydrofolic acid ((6S)-5-MTHF) is available in some commercial prenatal vitamins as an alternative to folic acid, but its effect on blood folate status during pregnancy is unknown. To address this, we randomised sixty pregnant individuals at 8–21 weeks’ gestation to 0·6 mg/d folic acid or (6S)-5-MTHF × 16 weeks. Fasting blood specimens were collected at baseline and after 16 weeks (endline). Erythrocyte and serum folate were quantified via microbiological assay (as globally recommended) and plasma unmetabolised folic acid (UMFA) via LC-MS/MS. Differences in biochemical folate markers between groups were explored using multivariable linear/quantile regression, adjusting for baseline concentrations, dietary folate intake and gestational weeks. At endline (n 54), the mean values and standard deviations (or median, inter-quartile range) of erythrocyte folate, serum folate and plasma UMFA (nmol/l) in those supplemented with (6S)-5-MTHF v. folic acid, respectively, were 1826 (sd 471) and 1998 (sd 421); 70 (sd 13) and 78 (sd 17); 0·5 (0·4, 0·8) and 1·3 (0·9, 2·1). In regression analyses, erythrocyte and serum folate did not differ by treatment group; however, concentrations of plasma UMFA in pregnancy were 0·6 nmol/l higher (95 % CI 0·2, 1·1) in those supplementing with folic acid as compared with (6S)-5-MTHF. In conclusion, supplementation with (6S)-5-MTHF may reduce plasma UMFA by ∼50 % as compared with supplementation with folic acid, the biological relevance of which is unclear. As folate is currently available for purchase in both forms, the impact of circulating maternal UMFA on perinatal outcomes needs to be determined.</description><subject>Acids</subject><subject>Blood</subject><subject>Canada</subject><subject>Chromatography, Liquid</subject><subject>Dietary intake</subject><subject>Dietary Supplements</subject><subject>Dihydrofolate reductase</subject><subject>Erythrocytes</subject><subject>Female</subject><subject>Fetuses</subject><subject>Folic Acid</subject><subject>Food fortification</subject><subject>Human and Clinical Nutrition</subject><subject>Humans</subject><subject>Informed consent</subject><subject>Metabolism</subject><subject>Microbiological assaying</subject><subject>Physiology</subject><subject>Plasma</subject><subject>Pregnancy</subject><subject>Pregnant Women</subject><subject>Public health</subject><subject>Regression analysis</subject><subject>Supplements</subject><subject>Tandem Mass Spectrometry</subject><subject>Vitamin B</subject><subject>Vitamins</subject><subject>Womens health</subject><issn>0007-1145</issn><issn>1475-2662</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>IKXGN</sourceid><sourceid>EIF</sourceid><recordid>eNp1ksmO1DAQQCMEYpqBD-CCLHEZDgEviRNzQy02aSQODeeoEpe7PUrsYDu0-pf5ChymWcSIk6tUr165ZBfFU0ZfMsqaVztKacNYVXNBcy7EvWLDqqYuuZT8frFZy-VavygexXiT05ZR9bC4EI2sFK_Ypvi-W-Z5xAldgmS9I0ebDuRK7l6UdTlhOpzGhCnA4aSDN360A4HBagLzjBAigUjQGByS_YZr8hdiHZnAZq911u1znDA4GFckhyTmgUskx4MdkQTUy7BSi8tDoc-WiPqO7WyYR4gTvCZAAjjtp59sCjaXvCFzwL0Dl8jR57XWxi040PC4eGBgjPjkfF4WX969_bz9UF5_ev9x--a6HComU2kYmqFlklcaK8MlGqQ1gtG8khRor3Hoa8UbrlohJG171bOmFlLzvlW1rsRlcXXrnYP_umBMXb7ggOMIDv0SO97WStKaMZbR5_-gN35ZV8yUoqJRStBVyG6pIfgYA5puDnaCcOoY7daP0N35CLnn2dm89BPq3x2_Xj4D4iyFqQ9W7_HP7P9rfwBtiMHX</recordid><startdate>20240114</startdate><enddate>20240114</enddate><creator>Cochrane, Kelsey M.</creator><creator>Elango, Rajavel</creator><creator>Devlin, Angela M.</creator><creator>Mayer, Chantal</creator><creator>Hutcheon, Jennifer A.</creator><creator>Karakochuk, Crystal D.</creator><general>Cambridge University Press</general><scope>IKXGN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5628-2850</orcidid></search><sort><creationdate>20240114</creationdate><title>Supplementation with (6S)-5-methyltetrahydrofolic acid appears as effective as folic acid in maintaining maternal folate status while reducing unmetabolised folic acid in maternal plasma: a randomised trial of pregnant women in Canada</title><author>Cochrane, Kelsey M. ; Elango, Rajavel ; Devlin, Angela M. ; Mayer, Chantal ; Hutcheon, Jennifer A. ; Karakochuk, Crystal D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-f1efc81624de4f26efe05eafd2460a0bdecb592729833608b9b17536d2b895d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Acids</topic><topic>Blood</topic><topic>Canada</topic><topic>Chromatography, Liquid</topic><topic>Dietary intake</topic><topic>Dietary Supplements</topic><topic>Dihydrofolate reductase</topic><topic>Erythrocytes</topic><topic>Female</topic><topic>Fetuses</topic><topic>Folic Acid</topic><topic>Food fortification</topic><topic>Human and Clinical Nutrition</topic><topic>Humans</topic><topic>Informed consent</topic><topic>Metabolism</topic><topic>Microbiological assaying</topic><topic>Physiology</topic><topic>Plasma</topic><topic>Pregnancy</topic><topic>Pregnant Women</topic><topic>Public health</topic><topic>Regression analysis</topic><topic>Supplements</topic><topic>Tandem Mass Spectrometry</topic><topic>Vitamin B</topic><topic>Vitamins</topic><topic>Womens health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cochrane, Kelsey M.</creatorcontrib><creatorcontrib>Elango, Rajavel</creatorcontrib><creatorcontrib>Devlin, Angela M.</creatorcontrib><creatorcontrib>Mayer, Chantal</creatorcontrib><creatorcontrib>Hutcheon, Jennifer A.</creatorcontrib><creatorcontrib>Karakochuk, Crystal D.</creatorcontrib><collection>Cambridge University Press Wholly Gold Open Access Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cochrane, Kelsey M.</au><au>Elango, Rajavel</au><au>Devlin, Angela M.</au><au>Mayer, Chantal</au><au>Hutcheon, Jennifer A.</au><au>Karakochuk, Crystal D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Supplementation with (6S)-5-methyltetrahydrofolic acid appears as effective as folic acid in maintaining maternal folate status while reducing unmetabolised folic acid in maternal plasma: a randomised trial of pregnant women in Canada</atitle><jtitle>British journal of nutrition</jtitle><addtitle>Br J Nutr</addtitle><date>2024-01-14</date><risdate>2024</risdate><volume>131</volume><issue>1</issue><spage>92</spage><epage>102</epage><pages>92-102</pages><issn>0007-1145</issn><eissn>1475-2662</eissn><abstract>Folic acid supplementation is recommended during pregnancy to support healthy fetal development; (6S)-5-methyltetrahydrofolic acid ((6S)-5-MTHF) is available in some commercial prenatal vitamins as an alternative to folic acid, but its effect on blood folate status during pregnancy is unknown. To address this, we randomised sixty pregnant individuals at 8–21 weeks’ gestation to 0·6 mg/d folic acid or (6S)-5-MTHF × 16 weeks. Fasting blood specimens were collected at baseline and after 16 weeks (endline). Erythrocyte and serum folate were quantified via microbiological assay (as globally recommended) and plasma unmetabolised folic acid (UMFA) via LC-MS/MS. Differences in biochemical folate markers between groups were explored using multivariable linear/quantile regression, adjusting for baseline concentrations, dietary folate intake and gestational weeks. At endline (n 54), the mean values and standard deviations (or median, inter-quartile range) of erythrocyte folate, serum folate and plasma UMFA (nmol/l) in those supplemented with (6S)-5-MTHF v. folic acid, respectively, were 1826 (sd 471) and 1998 (sd 421); 70 (sd 13) and 78 (sd 17); 0·5 (0·4, 0·8) and 1·3 (0·9, 2·1). In regression analyses, erythrocyte and serum folate did not differ by treatment group; however, concentrations of plasma UMFA in pregnancy were 0·6 nmol/l higher (95 % CI 0·2, 1·1) in those supplementing with folic acid as compared with (6S)-5-MTHF. In conclusion, supplementation with (6S)-5-MTHF may reduce plasma UMFA by ∼50 % as compared with supplementation with folic acid, the biological relevance of which is unclear. As folate is currently available for purchase in both forms, the impact of circulating maternal UMFA on perinatal outcomes needs to be determined.</abstract><cop>Cambridge, UK</cop><pub>Cambridge University Press</pub><pmid>37649241</pmid><doi>10.1017/S0007114523001733</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-5628-2850</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Acids Blood Canada Chromatography, Liquid Dietary intake Dietary Supplements Dihydrofolate reductase Erythrocytes Female Fetuses Folic Acid Food fortification Human and Clinical Nutrition Humans Informed consent Metabolism Microbiological assaying Physiology Plasma Pregnancy Pregnant Women Public health Regression analysis Supplements Tandem Mass Spectrometry Vitamin B Vitamins Womens health |
title | Supplementation with (6S)-5-methyltetrahydrofolic acid appears as effective as folic acid in maintaining maternal folate status while reducing unmetabolised folic acid in maternal plasma: a randomised trial of pregnant women in Canada |
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