Folate Supplementation: Too Much of a Good Thing?

Cancer Prevention Program, Fred Hutchinson Cancer Research Center, P.O. Box 19024, M4-B402, Seattle, Washington 98109-1024, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 03/2006; 15(2):189-93. DOI: 10.1158/1055-9965.EPI-152CO
Source: PubMed

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    • "Since 1998, countries like USA, Canada and Argentina (2002), have adopted flour fortification programs with extra vitamins to offset nutritional deficiencies (LeBlanc et al., 2010). Even though global public health efforts have focused on folate fortification and supplementation in order to prevent neural tube defects in early pregnancy, many countries have not adopted mandatory folic acid food fortification programs because this chemical form of the vitamin may mask early clinical manifestations of vitamin B12 deficiency (Bailey and Ayling, 2009; Morris and Tangney, 2007), alteration in the activity of the hepatic dihydrofolate reductase enzyme (Bailey and Ayling, 2009) or promote cancer (Baggott et al., 2012; Ulrich and Potter, 2006). Since natural folates, such as 5-methyltetrahydrofolate, that are normally found in foods and produced by microorganisms do not mask B12 deficiency (Scott, 1999), this folate form would be a more efficient and secure alternative than supplementation with folic acid (Lamers et al., 2006). "
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    ABSTRACT: The ability of 55 strains from different Lactobacillus species to produce folate was investigated. In order to evaluate folic acid productivity, lactobacilli were cultivated in the folate-free culture medium (FACM). Most of the tested strains needed folate for growth. The production and the extent of vitamin accumulation were distinctive features of individual strains. Lactobacillus amylovorus CRL887 was selected for further studies because of its ability to produce significantly higher concentrations of vitamin (81.2±5.4μg/L). The safety of this newly identified folate producing strain was evaluated through healthy experimental mice. No bacterial translocation was detected in liver and spleen after consumption of CRL887 during 7 days and no undesirable side effects were observed in the animals that received this strain. This strain in co-culture with previously selected folate producing starter cultures (Lactobacillus bulgaricus CRL871, and Streptococcus thermophilus CRL803 and CRL415) yielded a yogurt containing high folate concentrations (263.1±2.4μg/L); a single portion of which would provide 15% of the recommended dietary allowance. This is the first report where a Lactobacillus amylovorus strain was successfully used as co-culture for natural folate bio-enrichment of fermented milk.
    Full-text · Article · Aug 2014 · International Journal of Food Microbiology
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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.
    Full-text · Article · May 2014 · BioFactors
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    • "Taking into consideration the upper intake level, an adult who consumes two standard multivitamins daily (400 lg each) can easily exceed the daily upper intake level, as can a child who consumes substantial amounts of breakfast cereals which are usually folic acid supplemented. The intake of folic acid from fortified food (100–200 lg/d) together with the use of nutritional supplements creates a state of folate oversupplementation in a significant segment of the population (Ulrich and Potter 2006). This practice is occurring with little knowledge of the potential safety and physiologic consequences of chronic intake of such high doses of folic acid. "
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    ABSTRACT: Folic acid is the key one-carbon donor required for de novo nucleotide and methionine synthesis. Its deficiency is associated with megaloblastic anemia, cancer and various complications of pregnancy. However, its supplementation results in reduction of neural tube defects and prevention of several types of cancer. The intake of folic acid from fortified food together with the use of nutritional supplements creates a state of folate oversupplementation. Fortification of foods is occurring worldwide with little knowledge of the potential safety and physiologic consequences of intake of such high doses of folic acid. So, we planned to examine the effects of acute and chronic folate oversupplementation on the physiology of renal folate transport in rats. Male Wistar rats were procured and divided into two groups. Rats in group I were given semisynthetic diets containing 2 mg folic acid/kg diet (control) and those in group II were given folate-oversupplemented rat diet, i.e., 20 mg folic acid/kg diet (oversupplemented). Six animals from group I and group II received the treatment for 10 days (acute treatment) and remaining six for 60 days (chronic treatment). In acute folate-oversupplemented rats, 5-[(14)C]-methyltetrahydrofolate uptake was found to be significantly reduced, as compared to chronic folate-oversupplemented and control rats. This reduction in uptake was associated with a significant decrease in the mRNA and protein levels of the folate transporters. Results of the present investigation showed that acute oversupplementation led to a specific and significant down-regulation of renal folate uptake process mediated via transcriptional and translational regulatory mechanism(s).
    Full-text · Article · Jan 2014 · Genes & Nutrition
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