Folate Intake and Markers of Folate Status in Women of Reproductive Age, Pregnant and Lactating Women: A Meta-Analysis

Abstract

Background. Pregnant and breastfeeding women are at risk for folate deficiency. Folate supplementation has been shown to be associated with enhanced markers of folate status. However, dose-response analyses for adult women are still lacking. Objective. To assess the dose-response relationship between total folate intake (folic acid plus dietary folate) and markers of folate status (plasma/serum folate, red blood cell folate, and plasma homocysteine); to evaluate potential differences between women in childbearing age, pregnant and lactating women. Methods. Electronic literature searches were carried out on three databases until February 2010. The overall pooled regression coefficient (β) and SE(β) were calculated using meta-analysis on a double-log scale. Results. The majority of data was based on nonpregnant, nonlactating women in childbearingage. The pooled estimate of the relationship between folate intake and serum/plasma folate was 0.56 (95% CI = 0.40–0.72, P < 0.00001); that is, the doubling of folate intake increases the folate level in serum/plasma by 47%. For red blood cell folate, the pooled-effect estimate was 0.30 (95% CI = 0.22–0.38, P < 0.00001), that is, +23% for doubling intake. For plasma-homocysteine it was –0.10 (95% = –0.17 to –0.04, P = 0.001), that is, –7% for doubling the intake. Associations tended to be weaker in pregnant and lactating women. Conclusion. Significant relationships between folate intake and serum/plasma folate, red blood cell folate, and plasma homocysteine were quantified. This dose-response methodology may be applied for setting requirements for women in childbearing age, as well as for pregnant and lactating women.

Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects?

“…5-MethylTHF donates a methyl group to homocysteine (Hcy) that is converted into methionine and further to S-adenosylmethionine (SAM), the main methyl donor in the cell. The methylation of Hcy is mediated by the vitamin B 12 -dependent enzyme, methionine synthase. 5-MethylTHF is formed from the reduction of methylene-THF in a nicotinamide adenine dinucleotide phosphate-dependent reaction catalyzed by methylenetetrahydrofolate reductase (MTHFR).…”

“…Moreover, choline via its oxidation product, betaine, is also a methyl donor that is required for Hcy methylation to methionine via betaine homocysteine methyl transferase. Therefore, vitamins B 6 , B 12 , and B 2 , and betaine or choline are nutrients that interrelate to folate metabolism and may affect the NTD risk. Many supplements contain a combination of FA, B 12 , B 6 , and other nutrients.…”

“…A recent meta-analysis quantified the dose-response relationship between folate intake (dietary folate plus FA) and folate biomarkers in young, pregnant, and lactating women [12]. The aim was to establish a recommended intake for optimizing folate biomarkers for women planning for pregnancy.…”

“…In women aged 20-35 years, Wald et al [127] estimated that an increase in folate intake of 100 μg/day would increase serum folate concentrations by 0.94 μg/L (95% confidence interval 0.77-1.10) (2.13 nmol/L per 100 μg/day). Berti et al [12] estimated that a 100 μg/day total intake would increase serum folate level by 3.3 nmol/L. Lamers et al [69] estimated that, for a 100 μg [6S]-5-MTHF supplementation over 24 weeks, plasma folate concentrations increased by 9.6 nmol/L.…”

Folate status and health: challenges and opportunities

“…FA increases serum and red blood cell (RBC)-folate in a dose-, time-, and baseline-dependent manner [1]. The serum concentration of folate mirrors recent folate status, RBC-folate concentration is a long-term marker that reflects folate storage, and total homocysteine (tHcy) represents a surrogate functional markers for folate status [7]. Serum folate is preferred over RBC-folate because it can be reliably measured using immunological or chromatography methods, shows faster response after supplementation, and reflects the amount available for transfer via the placenta.…”