Is Folic Acid Good for Everyone?

Oxford Project to Investigate Memory and Ageing, Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 04/2008; 87(3):517-33.
Source: PubMed

ABSTRACT Fortification of food with folic acid to reduce the number of neural tube defects was introduced 10 y ago in North America. Many countries are considering whether to adopt this policy. When fortification is introduced, several hundred thousand people are exposed to an increased intake of folic acid for each neural tube defect pregnancy that is prevented. Are the benefits to the few outweighed by possible harm to some of the many exposed? In animals, a folic acid-rich diet can influence DNA and histone methylation, which leads to phenotypic changes in subsequent generations. In humans, increased folic acid intake leads to elevated blood concentrations of naturally occurring folates and of unmetabolized folic acid. High blood concentrations of folic acid may be related to decreased natural killer cell cytotoxicity, and high folate status may reduce the response to antifolate drugs used against malaria, rheumatoid arthritis, psoriasis, and cancer. In the elderly, a combination of high folate levels and low vitamin B-12 status may be associated with an increased risk of cognitive impairment and anemia and, in pregnant women, with an increased risk of insulin resistance and obesity in their children. Folate has a dual effect on cancer, protecting against cancer initiation but facilitating progression and growth of preneoplastic cells and subclinical cancers, which are common in the population. Thus, a high folic acid intake may be harmful for some people. Nations considering fortification should be cautious and stimulate further research to identify the effects, good and bad, caused by a high intake of folic acid from fortified food or dietary supplements. Only then can authorities develop the right strategies for the population as a whole.

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Available from: Helga Refsum, Mar 29, 2014
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    • "Folate/FA deficiency is linked to anemia, atherosclerosis, NTDs, adverse pregnancy outcomes, psychiatric disorders, and cancers (Bailey et al., 2003; Brito et al., 2012; Giovannucci, 2002; Reynolds, 2014), but FA intervention trials in humans are inconsistent and are not completely supportive of protective effects of FA supplementation except in the case of NTDs (Bønaa et al., 2006; Clarke et al., 2010; Lonn et al., 2006). Therefore, it has been questioned whether extra folic acid through food fortification is really beneficial to the majority of the population (Smith et al., 2008). Foods were fortified in the United States beginning in 1996 after the FDA approved fortification of grains at a dose of 140 ug FA/100 g of food to place approximately 100 ug FA more into the average adult diet (Table 1) (Hoyo et al., 2011a). "
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    ABSTRACT: Epigenetic mechanisms are now recognized to play roles in disease etiology. Several diseases increasing in frequency are associated with altered DNA methylation. DNA methylation is accomplished through metabolism of methyl donors such as folate, vitamin B12, methionine, betaine (trimethylglycine), and choline. Increased intake of these compounds correlates with decreased neural tube defects, although this mechanism is not well understood. Consumption of these methyl donor pathway components has increased in recent years due to fortification of grains and high supplemental levels of these compounds (e.g. vitamins, energy drinks). Additionally, people with mutations in one of the enzymes that assists in the methyl donor pathway (5-MTHFR) are directed to consume higher amounts of methyl donors to compensate. Recent evidence suggests that high levels of methyl donor intake may also have detrimental effects. Individualized medicine may be necessary to determine the appropriate amounts of methyl donors to be consumed, particularly in women of child bearing age. Copyright © 2015. Published by Elsevier Ltd.
    Progress in Biophysics and Molecular Biology 04/2015; 118(1-2). DOI:10.1016/j.pbiomolbio.2015.03.007 · 2.27 Impact Factor
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    • "Folic acid, the synthetic form of folate vitamin, either from supplements or fortification, has been shown to reduce the incidence of neural tube defects in pregnancies (MRC, 1991; Ray et al., 2002). However, an excess of the synthetic form of folate for the population as a whole may not necessarily be beneficial (Smith et al., 2008). There are several studies that seem to indicate a potential risk of excess synthetic folic acid intake (Mason et al., 2007; Wien et al., 2012). "
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    ABSTRACT: A simple separation process was used to fractionate egg yolk into plasma and granule fractions through the use of gravitational separation with laboratory- or pilot-scale centrifuges. The granule fractions at pilot-scale presented with higher protein concentrations (66–69%) and lower lipid contents (20–26%), on a dry basis, as compared to the plasma fraction. The recovery of protein, based on the raw material (egg yolk), was calculated to be 96% and 89% for the laboratory- and pilot-scale fractionation processes, respectively. Good agreement was achieved between the laboratory- and pilot-scale centrifugation processes, in terms of chemical composition and recovery of egg yolk components. The plasma fraction preserved 66–71% of the lipid with the laboratory-scale and 75–77% with the pilot-scale fractionation process. It was confirmed by SDS–PAGE and 2D-gel electrophoresis analysis that each egg yolk fraction incorporated different amount of LDL and HDL. SDS–PAGE and 2D-gel electrophoresis analysis revealed different profile patterns for the plasma and granule fractions. Folate content in plasma and granule fractions was measured using HPLC analysis. Folate analysis revealed that the plasma fraction of egg yolk was devoid of folate (5-CH3-H4folate), whereas the granule fraction was concentrated by a 3-fold factor in comparison to native egg yolk.
    Journal of Food Engineering 11/2014; 141:85–92. DOI:10.1016/j.jfoodeng.2014.05.011 · 2.77 Impact Factor
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    • "Addition of these nutrients to flour appears to have dramatically reduced neural tube defects [1], and deficiencies are also thought to contribute to neuro-cognitive disorders [21]. However, this study adds to a growing number of recent studies suggesting deleterious effects of developmental exposure to high doses of these compounds [2], [22], [23], [24], [25], [26], [27], [28]. For example, mutations in some loci involved in neural tube development are exacerbated (rather than rescued) by excess folic acid [24], and neurons developmentally exposed to high folic acid may be more susceptible to seizure [26]. "
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    ABSTRACT: Folate and other methyl-donor pathway components are widely supplemented due to their ability to prevent prenatal neural tube defects. Several lines of evidence suggest that these supplements act through epigenetic mechanisms (e.g. altering DNA methylation). Primary among these are the experiments on the mouse viable yellow allele of the agouti locus (Avy). In the Avy allele, an Intracisternal A-particle retroelement has inserted into the genome adjacent to the agouti gene and is preferentially methylated. To further test these effects, we tested the same diet used in the Avy studies on wild-derived Peromyscus maniculatus, a native North American rodent. We collected tissues from neonatal offspring whose parents were fed the high-methyl donor diet as well as controls. In addition, we assayed coat-color of a natural variant (wide-band agouti = ANb) that overexpresses agouti as a phenotypic biomarker. Our data indicate that these dietary components affected agouti protein production, despite the lack of a retroelement at this locus. Surprisingly, the methyl-donor diet was associated with defects (e.g. ovarian cysts, cataracts) and increased mortality. We also assessed the effects of the diet on behavior: We scored animals in open field and social interaction tests. We observed significant increases in female repetitive behaviors. Thus these data add to a growing number of studies that suggest that these ubiquitously added nutrients may be a human health concern.
    PLoS ONE 08/2014; 9(8):e104942. DOI:10.1371/journal.pone.0104942 · 3.23 Impact Factor
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