Contemporary Issues Surrounding Folic Acid Fortification Initiatives

Choi, Jeong-Hwa; Yates, Zoë; Veysey, Martin; Heo, Young Ran; Lucock, Mark

doi:10.3746/pnf.2014.19.4.247

Cited by 74 publications

(55 citation statements)

References 171 publications

(195 reference statements)

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“…Our findings are confirmed by the study by Stolen et al [38] reporting similar results. As there is discussion on the safety of high concentrations [38,39,] it deserves due consideration to lower folic acid amounts in AAM. For example, high levels of folic acid have been associated with interference in DNA and histone methylation, decreased natural killer cell toxicity, an increased risk of cognitive impairment in the elderly and facilitating progression of preneoplastic cells and subclinical cancers.…”

Section: Discussionmentioning

confidence: 99%

Micronutrients, Essential Fatty Acids and Bone Health in Phenylketonuria

et al. 2017

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Introduction: In phenylketonuria (PKU), a natural protein-restricted dietary treatment prevents severe cognitive impairment. Nutrient deficiencies may occur due to strict diet. This study is aimed at evaluating the dietary intake and blood concentrations of micronutrients and essential fatty acids (FA), bone mineral density (BMD) and fracture history in patients on long-term dietary treatment. Methods: Sixty early diagnosed Dutch patients (aged 1-39 years) were included in a multi-center cross-sectional study. Their dietary intake, blood concentrations of micronutrients, FA, fracture history and BMD were assessed. Results: Selenium dietary intake and serum concentrations were low in 14 and 46% of patients, respectively. The serum 25-OH vitamin D2 + D3 concentration was low in 14% of patients while 20% of patients had a low vitamin D intake. Zinc serum concentrations were below normal in 14% of patients, despite adequate intake. Folic acid serum concentrations and intake were elevated. Despite safe total protein and fat intake, arginine plasma concentrations and erythrocyte eicosapentaenoic acid were below reference values in 19 and 6% of patients, respectively. Low BMD (Z-score <-2) was slightly more prevalent in patients, but the lifetime fracture prevalence was comparable to the general population. Conclusions: Dutch patients with PKU on long-term dietary treatment have a near normal nutrient status. Supplementation of micronutrients of which deficiency may be deleterious (e.g., vitamin D and selenium) should be considered. BMD warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

Micronutrients, Essential Fatty Acids and Bone Health in Phenylketonuria

et al. 2017

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“…4 Like 5-MTHF, FA is also metabolized to THF; however, it is via a much 'slower' twostep process catalyzed by the enzyme dihydrofolate reductase and producing the intermediate dihydrofolate (DHF). 20 Consequently, human ability to absorb and process FA to biologically active forms of folate is saturated at daily intakes of between 266-400 µg. 21, 22 Folinic acid is another form of folate supplement available and is commonly used after methotrexate treatment for various types of cancers.…”

Section: Types Of Folatementioning

confidence: 99%

“…DHF is the intermediate metabolite in FA metabolism and acts to inhibit key enzymes in the folate cycle, while slowing down the biotransformation of FA to its active forms. 20 The possible consequences may be that non-metabolized FA in the plasma is left to compete with biologically active forms for transport into the central nervous system, and that intracellular folate metabolism is impaired by the FA intermediates. 4, 21 Moreover, the MTHFR gene has been extensively studied due to the observation that carriers of the C677T variant have reduced enzyme function, resulting in both increased levels of Hcy and an increased risk of depression.…”

Section: Future Research Directionsmentioning

confidence: 99%

Effect of Folate Supplementation on Inflammatory Markers in Individuals Susceptible to Depression: A Systematic Review

Barnett¹,

D’Cunha

Georgousopoulou

et al. 2017

Exploratory Research and Hypothesis in Medicine

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Folate has been proposed to be an efficacious treatment strategy for depression. The mandatory fortification of flour with synthetic folic acid (FA) in over 80 countries has yielded improvements in folate intake; however, depression is still a considerable public health concern. While there are established benefits of FA fortification in reducing risk of neural tube defects, the implications regarding depression are unclear, especially in individuals with certain genetic polymorphisms. Therefore, a systematic review was conducted to examine the effects of folate to treat depression. Following PRISMA guidelines, a systematic review was conducted of electronic databases (PUBMED, Scopus, CINAHL, and Cochrane Library) to identify human clinical trials examining the effects of folate (including FA) supplementation in the management or prevention of depression, the impact on inflammatory markers and if genetic polymorphisms were considered. Ten trials met the inclusion criteria. Seven trials examined effects of either adjunctive FA or L-methylfolate (L-MTHF) supplementation with antidepressants in the management of depression and three examined effects of FA supplementation alone for prevention of depression. No benefit of FA was found compared to placebo (all, p > 0.05). The single L-MTHF trial that explored the interplay of genetic polymorphisms and methylation status found benefit in the Hamilton depression rating scale from adjunctive treatment with 15 mg/day of L-MTHF compared with placebo (−6.8 ± 7.2 vs. −3.7 ± 6.5; p = 0.017) and improvement with L-MTHF for most genetic markers. Currently, there is no evidence to support FA supplementation for the management or prevention of depression. More research is required to determine the efficacy of L-MTHF and folinic acid in certain clinical populations.

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“…It is therefore very stable under the majority of conditions (i.e, temperature and pH), and is the vitamer used for supplements and food fortification (8,9). Due to its specific physico-chemical and metabolic characteristics, the initial absorption and metabolism differs from that of natural methylfolate.…”

mentioning

confidence: 99%

Gene-Nutrient Interaction between Folate and Dihydrofolate Reductase in Risk for Adenomatous Polyp Occurrence: A Preliminary Report

Choi¹,

Yates

Martin³

et al. 2015

J Nutr Sci Vitaminol

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Summary Folate and related gene variants are significant risk factors in the aetiology of colorectal cancer. Dihydrofolate reductase (DHFR) is critical in the metabolism of synthetic folic acid (pteroylmonoglutamatamic, PteGlu) to tetrahydrofolate following absorption. Therefore, the 19bp deletion variant of DHFR may lead to the alteration of folate-related colorectal disease susceptibility. This study examined the association between PteGlu and 19bp del-DHFR, and adenomatous polyp (AP) occurrence, an antecedent of colorectal cancer. A total of 199 subjects (162 controls and 37 AP cases) were analysed to determine dietary intake of total folate, natural methylfolate and synthetic PteGlu, level of erythrocyte folate and plasma homocysteine (tHcy), and genotype of 19bp del-DHFR. Dietary folate intake, erythrocyte folate, tHcy and 19bp del-DHFR variants did not independently predict the occurrence of AP. However, a gene-nutrient interaction was observed when subjects were stratified according to dietary folate intake. In subjects with a folate intake above the median value due to significant dietary PteGlu content, the presence of the 19bp-deletion allele decreased the risk for AP (OR50.35, 95% CI: 0.13-0.97). However, such association was not evident in individuals with a folate intake below the median value. In conclusion, the finding suggests that folate nutrition and 19bp del-DHFR variation may interact to modify AP risk.

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Contemporary Issues Surrounding Folic Acid Fortification Initiatives

Cited by 74 publications

References 171 publications

Micronutrients, Essential Fatty Acids and Bone Health in Phenylketonuria

Micronutrients, Essential Fatty Acids and Bone Health in Phenylketonuria

Effect of Folate Supplementation on Inflammatory Markers in Individuals Susceptible to Depression: A Systematic Review

Gene-Nutrient Interaction between Folate and Dihydrofolate Reductase in Risk for Adenomatous Polyp Occurrence: A Preliminary Report

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