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: 6.92). 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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    • "In humans, excess in FA intake via supplementation has been associated with cognitive decline (Morris et al., 2005), and is suggested as a factor impairing normal folate function (Kim, 2005). Overall, changes in folate status have epigenetic effects by altering DNA methylation in animals and humans with tissue-, site-, and gene-specific pathways (McCabe & Caudill, 2005; Smith et al., 2008), and evidence exists that DNA methylation during fetus development consists of a dynamic process influenced by the maternal folate/methylation status (Smith et al., 2008). Therefore caution should be taken in FA supplementation during pregnancy and each effort for supplement use should be supervised by a physician and accompanied by evaluation of the maternal folate stores. "
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    ABSTRACT: ABSTRACT Background/Aim: Maternal diet is important in the outcome of pregnancy and the health of the children. The present cross-sectional study aimed to assess the use of dietary supplements during pregnancy and define the maternal characteristics associated with supplement use. Methods: The diet of 100 childbearing women was recorded for three consecutive days and micronutrient supplementation was added to the dietary intake and the median values were used in the analyses. Results: The majority of the participants (92%) consumed at least one supplement. Supplementation of folic acid (FA) was significantly lower during the third trimester compared to the second (p ≤ .007). Higher intake of Ca and Fe supplements was observed in the second trimester (p ≤ .001). The use of supplements contributed to an attenuated consumption of all reported micronutrients (Mg, Ca, FA, and Fe, p ≤ .001). The principal components analysis revealed that the most important factor contributing to supplementation was primiparity. Conclusions: Overall, a high prevalence of micronutrient supplementation during pregnancy was observed without ensuring adequacy in the micronutrient intake. The increased rates of supplement users might be the result of an act for balancing diet in unplanned pregnancies.
    Journal of Dietary Supplements 06/2014; 11(2):155-65. DOI:10.3109/19390211.2013.859210
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    • "for the older adult population (Smith et al., 2008) and to those suffering from pernicious anemia, which is quite common (Morris, 2012b). The folic acid will reduce Hcy levels but mask B12 deficiency , which if not treated will result in peripheral neuropathy, tiredness, lack of energy, and permanent cognitive deficits. "
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    ABSTRACT: Few B-vitamin trials to lower homocysteine (Hcy) have reported evidence of beneficial effects on cognition in older adults with cognitive impairment or Alzheimer's disease. This article reviews the role of Hcy in cognitive decline. It also considers some reasons why meta-analyses have failed to find effects of B-vitamin treatment. Findings from the successful VITACOG trial are examined from a new perspective of critical levels of Hcy and brain atrophy that may impact on the efficacy of B-vitamin treatment. It appears that there is a critical level of brain shrinkage, possibly mediated by elevated Hcy, which when reached, results in cognitive decline, especially in episodic memory performance. Supplements, food sources, and effects of folic acid fortification are discussed in relation to B12 deficiency.
    Neurobiology of Aging 05/2014; 35. DOI:10.1016/j.neurobiolaging.2014.03.040 · 4.85 Impact Factor
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    • "High plasma levels of un-metabolized folic acid can lead to a build-up of dihydrofolate in the cell, which has been shown to inhibit MTHFR [42] and thereby inhibiting remethylation of homocysteine. Thus, it has been postulated that high plasma concentrations of folic acid may lead to a " functional " folate deficiency [43] [44]. Folate supplementation in the form of 5- methylTHF has been shown to effectively raise plasma folate levels without leading to an elevation in un-metabolized folic acid [45] [46]. "
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    ABSTRACT: Folate is an essential B vitamin required for the maintenance of AdoMet-dependent methylation. The liver is responsible for many methylation reactions that are used for post-translational modification of proteins, methylation of DNA, and the synthesis of hormones, creatine, carnitine, and phosphatidylcholine. Conditions where methylation capacity is compromised, including folate deficiency, are associated with impaired phosphatidylcholine synthesis resulting in non-alcoholic fatty liver disease and steatohepatitis. In addition, folate intake and folate status have been associated with changes in the expression of genes involved in lipid metabolism, obesity, and metabolic syndrome. In this review, we provide insight on the relationship between folate and lipid metabolism, and an outlook for the future of lipid-related folate research. © 2013 BioFactors, 2013.
    BioFactors 05/2014; 40(3). DOI:10.1002/biof.1154 · 3.00 Impact Factor
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