The relationship between increased folate catabolism and the increased requirement for folate in pregnancy

Higgins, John R.; Quinlivan, Eoin P.; McPartlin, Joseph; Scott, John M.; Weir, Donald G.; Darling, Michael

doi:10.1111/j.1471-0528.2000.tb11115.x

Cited by 53 publications

(45 citation statements)

References 13 publications

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“…Although adult carriers of MTHFR polymorphisms only have a mildly disturbed folate metabolism due to decreased MTHFR activity, our data suggest that the effect of one or more MTHFR mutated alleles may be detrimental during embryogenesis when the folate requirement is high. 29,30 The 677TT/1298AA and 677CT/1298AC genotypes that result in elevated homocysteine in adults 3,19 also tended to be more frequent in the spontaneous abortion group when compared with controls but did not reach statistical significance. However, when combining the observed frequencies of the 677TT/1298AA and 677CT/1298AC genotypes there was a significant difference between the spontaneous abortion and control groups, suggesting that these genotypes are involved in the pathogenesis of spontaneous abortion.…”

Section: Discussionmentioning

confidence: 96%

Increased frequency of combined methylenetetrahydrofolate reductase C677T and A1298C mutated alleles in spontaneously aborted embryos

et al. 2002

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The pathogenesis of spontaneous abortion is complex, presumably involving the interaction of several genetic and environmental factors. The methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms are commonly associated with defects in folate dependent homocysteine metabolism and have been implicated as risk factors for recurrent embryo loss in early pregnancy. In the present study we have determined the prevalence of combined MTHFR C677T and A1298C polymorphisms in DNA samples from spontaneously aborted embryos (foetal death between sixth and twentieth week after conception) and adult controls using solid-phase minisequencing technique. There was a significant odds ratio of 14.2 (95% CI 1.78-113) in spontaneously aborted embryos comparing the prevalence of one or more 677T and 1298C alleles vs the wild type combined genotype (677CC/1298AA), indicating that the MTHFR polymorphisms may have a major impact on foetal survival. Combined 677CT/1298CC, 677TT/1298AC or 677TT/1298CC genotypes, which contain three or four mutant alleles, were not detected in any of the groups, suggesting complete linkage disequilibrium between the two polymorphisms. The present finding of high prevalence of mutated MTHFR genotypes in spontaneously aborted embryos emphasises the potential protective role of periconceptional folic acid supplementation.

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Section: Discussionmentioning

confidence: 96%

Increased frequency of combined methylenetetrahydrofolate reductase C677T and A1298C mutated alleles in spontaneously aborted embryos

et al. 2002

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“…Since BMI is positively associated with RBC folate but inversely associated with serum folate, the observed associations between folate status and pregnancy complications may be overestimated if serum folate is used while underestimated if RBC folate is used. Folate status varies substantially during pregnancy (8) , which can further complicate the accurate assessment of folate status.…”

Section: Discussionmentioning

confidence: 99%

“…It was observed that the peak serum folate concentrations of obese and normal-weight women were statistically different after a single oral dose of folic acid (0·4 mg), but there was no difference in overall area under the curve, indicating that obesity does not impair the absorption of folic acid but may lead to redistribution of folate from circulation into tissue. Folate requirements are higher in pregnancy in order to maintain placental and fetal growth, and accelerated folate catabolism and haemodilution during pregnancy can also result in decreased circulating folate concentrations (8)(9)(10) . Given the potential physiological and pharmacokinetic differences in pregnant v. non-pregnant populations, the association of obesity with serum and RBC folate concentrations may be altered.…”

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confidence: 99%

Serum and red-blood-cell folate demonstrate differential associations with BMI in pregnant women

Shen

Chaudhry

MacFarlane

et al. 2016

Public Health Nutr.

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Objective: To examine the association between BMI and folate concentrations in serum and red blood cells (RBC) in pregnant women. Design: A cross-sectional comparison of folate concentrations in serum and RBC sampled simultaneously from the same individual. Setting: The Ottawa Hospital and Kingston General Hospital, Ontario, Canada. Subjects: Pregnant women recruited between 12 and 20 weeks of gestation. Results: A total of 869 pregnant women recruited from April 2008 to April 2009 were included in the final analysis. Serum folate was inversely associated and RBC folate positively associated with BMI, after adjusting for folic acid supplementation, age, gestational age at blood sample collection, race, maternal education, annual income, smoking and MTHFR 677C→T genotype. In stratified analyses, this differential association was significant in women with the MTHFR CC variant. In women with the CT and TT variants, the differential associations were in the same direction but not significant. Folic acid supplementation during pregnancy did not alter the differential association of BMI with serum and RBC folate concentration. This indicates that the current RBC folate cut-off approach for assessing risk of neural tube defects in obese women may be limited. Conclusions: BMI is inversely associated with serum folate and positively associated with RBC folate in pregnant women, especially for those with the MTHFR CC variant.

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“…In addition, Willoughby and Jewell (55) reported that the minimum dose of folate needed during late pregnancy, in addition to a dietary folate intake of 50 mg per day, was close to 300 mg/d. Increased folate catabolism and urinary folate excretion have been reported (56,57), which also may contribute to increased folate needs in pregnancy. However, these findings are controversial.…”

Section: Folatementioning

confidence: 99%

Urinary Excretion Levels of Water-Soluble Vitamins in Pregnant and Lactating Women in Japan

Shibata

Fukuwatari

Sasaki

et al. 2013

J Nutr Sci Vitaminol

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Dietary habits of pregnant and lactating women have a critical impact on the health of future infants. For this reason, the Japanese Dietary Reference Intakes regarding the amounts of addition of water-soluble vitamins have been set (1). The additional intake amounts for pregnant and lactating women were calculated based on data concerning the changes in the metabolic characteristics of vitamins in pregnant women and the loss of vitamins as a result of lactation. However, there is little information about whether nutritional statuses of water-soluble-vitamins in Japanese pregnant and lactating women are good or not. Therefore, we examined the nutritional status of pregnant and lactating women and speculated about the validity of the additional amount of some water-soluble vitamins in the dietary reference intakes for pregnant and lactating women.A potential approach for determining the validity for the additional amounts is based on the observation that a water-soluble vitamin or its catabolite(s) can be detected in the urine (2-11). Using this approach, the urinary excretion of a water-soluble vitamin or its catabolite(s) occurs when the dietary intake exceeds an individual necessary amount. MATERIALS AND METHODSSubjects. Japanese pregnant (16-40 wk gestation) or lactating women (0-11 mo postpartum) were recruited from a parenting circle in The University of Shiga Prefecture between April 2010 and February 2012. Japanese married non-pregnant, non-lactating women also were recruited as controls through the parenting circle to match the mean ages and heights of the pregnant and lactating women. The purpose and protocol of this study was explained to all participants before joining the study, and written informed consent was obtained from each participant. We excluded participants diagnosed with a cold or influenza, and those who had taken multi-vitamin supplements at least once during the previous month. In addition, we excluded participants whose 24-h urine collection was considered incomplete: a collection time outside the 22-26-h range, urine volume ,250 mL, or extremely low or high energy intake (,500 or .4,000 kcal/d) (12). Twenty-four of the 2nd trimester pregnant (16-27 wk gestation) and 32 of the Bunkyo-ku, Tokyo 113-0033, Japan (Received December 17, 2012) Summary Recent studies have shown that the urinary excretion levels of water-soluble vitamins can be used as biomarkers for the nutritional status of these vitamins. To determine changes in the urinary excretion levels of water-soluble vitamins during pregnant and lactating stages, we surveyed and compared levels of nine water-soluble vitamins in control (non-pregnant and non-lactating women), pregnant and lactating women. Control women (n537), women in the 2nd (16-27 wk, n524) and 3rd trimester of pregnancy (over 28 wk, n532), and early-(0-5 mo, n554) and late-stage lactating (6-11 mo, n549) women took part in the survey. The mean age of subjects was ~30 y, and mean height was ~160 cm. A single 24-h urine sample was collected 1 d after the comple...

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The relationship between increased folate catabolism and the increased requirement for folate in pregnancy

Cited by 53 publications

References 13 publications

Increased frequency of combined methylenetetrahydrofolate reductase C677T and A1298C mutated alleles in spontaneously aborted embryos

Increased frequency of combined methylenetetrahydrofolate reductase C677T and A1298C mutated alleles in spontaneously aborted embryos

Serum and red-blood-cell folate demonstrate differential associations with BMI in pregnant women

Urinary Excretion Levels of Water-Soluble Vitamins in Pregnant and Lactating Women in Japan

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