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


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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    • "High folate levels may also interfere with the anti-folate medications prescribed for a number of conditions (e.g., rheumatoid arthritis, psoriasis, cancer, bacterial infections, malaria) and exert biphasic effects with regards to cancer; conferring protection at lower concentrations but increasing carcinogenesis at higher concentrations. However, to date there is no consensus as to the blood levels of folates that might cause harm[103]. The upper limit for niacin is set at 35 mg (US/Canada), with this predicated simply on its ability to cause temporary flushing of the skin at doses in excess of 100 mg, although nausea, vomiting, diarrhoea and in very rare cases liver damage have been noted following extended consumption of doses of a gram and more[8]. "

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    • "Mandatory food fortification with folic acid is debated in some countries because of the suggested cancer risk in adults (Kim, 2004; Mason et al, 2007; Smith et al, 2008). However, in case–control studies on children, cancer risks (leukemia, brain tumours) were reduced if the mother had been exposed to perigestational maternal folic acid supplementation (Thompson et al, 2001; Milne et al, 2010; Milne et al, 2012; Metayer et al, 2014). "
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    ABSTRACT: Background: We investigated the association between supplemental folic acid in pregnancy and childhood cancer in a nation-wide study of 687 406 live births in Norway, 1999-2010, and 799 children diagnosed later with cancer. Methods: Adjusted hazard ratios (HRs) compared cancer risk in children by approximated periconceptional folic acid levels (folic acid tablets and multivitamins (0.6 mg), only folic acid (0.4 mg), only multivitamins (0.2 mg)) and cancer risk in unexposed. Results: Any folic acid levels were not associated with leukemia (e.g., high-level folic acid HR 1.25; 95% CI 0.89-1.76, PTrend 0.20), lymphoma (HR 0.96; 95% CI 0.42-2.21, PTrend 0.51), central nervous system tumours (HR 0.68; 95% CI 0.42-1.10, PTrend 0.32), neuroblastoma (HR 1.05; 95% CI 0.53-2.06, PTrend 0.85), Wilms' tumour (HR 1.16; 95% CI 0.52-2.58, PTrend 0.76), or soft-tissue tumours (HR 0.77; 95% CI 0.34-1.75, PTrend 0.90). Conclusions: Folic acid supplementation was not associated with risk of major childhood cancers.
    Preview · Article · Jan 2016 · British Journal of Cancer
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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.
    Full-text · Article · Apr 2015 · Progress in Biophysics and Molecular Biology
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