Folate-Binding Protein in Milk: A Review of Biochemistry, Physiology, and Analytical Methods

Nygren-Babol, Linnéa; Jägerstad, Margaretha

doi:10.1080/10408398.2010.500499

Cited by 37 publications

(28 citation statements)

References 103 publications

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“…The maintenance of breast-milk total folate concentrations in the midst of rising breast-milk FA concentrations implies that FA is displacing reduced folate forms from FRa in breast milk. The high percentage of breast-milk FA (w40%) that arose from the study FA dose may be of concern because some bioavailability studies with milk have suggested that the absorption of FA could be less than that of 5-methyl-THF when bound to FRa (40).…”

Section: Breast-milk Folatementioning

confidence: 98%

Folate-status response to a controlled folate intake in nonpregnant, pregnant, and lactating women

West¹,

Yan²,

Perry³

et al. 2012

The American Journal of Clinical Nutrition

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The consumption of the study folate dose yielded a supranutritional folate status regardless of the physiologic state. Based on urinary folate excretion, folate use was greatest to least: pregnant > lactating > nonpregnant women. Breast-milk folate species were responsive to maternal folate intake, and FA made up ~40% of breast-milk total folate at study end. These findings warrant revisiting prenatal supplement FA formulation in populations exposed to FA-fortification programs.

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Section: Breast-milk Folatementioning

confidence: 98%

Folate-status response to a controlled folate intake in nonpregnant, pregnant, and lactating women

West¹,

Yan²,

Perry³

et al. 2012

The American Journal of Clinical Nutrition

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show abstract

“…The presence of UMFA in breastmilk is concerning because it may impair the bioavailability of folate in milk [35,36]. Folate-binding protein (FBP) in breastmilk has a higher affinity for folic acid than reduced folate forms; after ingestion, folic acid may be less readily released by FBP as it passes through the gastrointestinal tract, reducing subsequent absorption and potentially impacting the infant's folate status [33].…”

Section: Periconceptional Folate Requirementsmentioning

confidence: 99%

Is natural (6S)-5-methyltetrahydrofolic acid as effective as synthetic folic acid in increasing serum and red blood cell folate concentrations during pregnancy? A proof-of-concept pilot study

Cochrane

Mayer

Devlin

et al. 2020

Trials

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Background: North American health authorities recommend 0.4 mg/day folic acid before conception and throughout pregnancy to reduce the risk of neural tube defects. Folic acid is a synthetic form of folate that must be reduced by dihydrofolate reductase and then further metabolized. Recent evidence suggests that the maximal capacity for this process is limited and unmetabolized folic acid has been detected in the circulation. The biological effects of unmetabolized folic acid are unknown. A natural form of folate, (6S)-5-methyltetrahydrofolic acid (Metafolin®), may be a superior alternative because it does not need to be reduced in the small intestine. Metafolin® is currently used in some prenatal multivitamins; however, it has yet to be evaluated during pregnancy. Methods/design: This double-blind, randomized trial will recruit 60 pregnant women aged 19-42 years. The women will receive either 0.6 mg/day folic acid or an equimolar dose (0.625 mg/day) of (6S)-5-methyltetrahydrofolic acid for 16 weeks. The trial will be initiated at 8-21 weeks' gestation (after neural tube closure) to reduce the risk of harm should (6S)-5methyltetrahydrofolic acid prove less effective. All women will also receive a prenatal multivitamin (not containing folate) to ensure adequacy of other nutrients. Baseline and endline blood samples will be collected to assess primary outcome measures, including serum folate, red blood cell folate and unmetabolized folic acid. The extent to which the change in primary outcomes from baseline to endline differs between treatment groups, controlling for baseline level, will be estimated using linear regression. Participants will have the option to continue supplementing until 1 week postpartum to provide a breastmilk and blood sample. Exploratory analyses will be completed to evaluate breastmilk and postpartum blood folate concentrations.

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“…33,34 Presence of UMFA in breastmilk is concerning because it may impair bioavailability of folate in milk. 35,36 Folate binding protein (FBP) in breastmilk has a higher affinity for folic acid than reduced folate forms; after ingestion, folic acid may be less readily released by FBP as it passes through the gastrointestinal tract, reducing subsequent absorption and potentially impacting the infant's folate status. 33 Although total breastmilk folate concentrations are unaffected by maternal folate status (except in cases of severe deficiency) 34,37 , the proportion breastmilk folate as folic acid may be influenced.…”

Section: Periconceptional Folate Requirementsmentioning

confidence: 99%

Is natural (6S)-5-methyltetrahydrofolic acid as effective as synthetic folic acid in increasing serum and red blood cell folate concentrations during pregnancy? A proof-of-concept pilot study

Cochrane

Mayer

Devlin

et al. 2020

Preprint

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Background: North American health authorities recommend 0.4 mg/day folic acid before conception and throughout pregnancy to reduce the risk of neural tube defects. Folic acid is a synthetic form of folate that must be reduced by dihydrofolate reductase and then further metabolized. Recent evidence suggests that the maximal capacity for this process is limited and unmetabolized folic acid has been detected in circulation. The biological effects of unmetabolized folic acid are unknown. A natural form of folate, (6S)-5-methyltetrahydrofolic acid (Metafolin®), may be a superior alternative because it does not need to be reduced in the small intestine. Metafolin® is currently used in some prenatal multivitamins, however it has yet to be evaluated during pregnancy. Methods: This double-blind randomized trial will recruit 60 pregnant women aged 19-42 years. Women will receive either 0.6 mg/day folic acid or an equimolar dose (0.625 mg/day) of (6S)-5-methyltetrahydrofolic acid for 16-weeks. The trial will be initiated at 8-21 weeks gestation (after neural tube closure) to reduce the risk of harm should (6S)-5-methyltetrahydrofolic acid prove less effective. All women will also receive a prenatal multivitamin (not containing folate) to ensure adequacy of other nutrients. Baseline and endline blood samples will be collected to assess primary outcome measures, including serum folate, red blood cell folate and unmetabolized folic acid. The extent to which the change in primary outcomes from baseline to endline differs between treatment groups, controlling for baseline level, will be estimated using linear regression. Participants will have the option to continue supplementing until 1-week postpartum to provide a breastmilk and blood sample. Exploratory analyses will be completed to evaluate breastmilk and postpartum blood folate concentrations. Discussion: This proof-of-concept trial is needed to obtain estimates of the effect of (6S)-5-methyltetrahydrofolic acid compared to folic acid on circulating biomarkers of folate status during pregnancy. These estimates will inform the design of a definitive trial which will be powered to assess whether (6S)-5-methyltetrahydrofolic acid is as effective as folic acid in raising blood folate concentrations during pregnancy. Ultimately, these findings will inform folate supplementation policies for pregnant women.

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Folate-Binding Protein in Milk: A Review of Biochemistry, Physiology, and Analytical Methods

Cited by 37 publications

References 103 publications

Folate-status response to a controlled folate intake in nonpregnant, pregnant, and lactating women

Folate-status response to a controlled folate intake in nonpregnant, pregnant, and lactating women

Is natural (6S)-5-methyltetrahydrofolic acid as effective as synthetic folic acid in increasing serum and red blood cell folate concentrations during pregnancy? A proof-of-concept pilot study

Is natural (6S)-5-methyltetrahydrofolic acid as effective as synthetic folic acid in increasing serum and red blood cell folate concentrations during pregnancy? A proof-of-concept pilot study

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