Too much folate: a risk factor for cancer and cardiovascular disease? Curr Opin Clin Nutr Metab Care

Vitamins and Carcinogenesis Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 02111, USA.
Current opinion in clinical nutrition and metabolic care 02/2009; 12(1):30-6. DOI: 10.1097/MCO.0b013e32831cec62
Source: PubMed


The intent of this evidence-based review is to analyze the role of folate in chronic diseases, focusing on cancer and cardiovascular disease.
Low folate status has been shown to be a risk factor for cancer and cardiovascular disease. Although epidemiological data suggest an inverse association between folate status and disease risk, intervention studies give equivocal results, suggesting the response to folate intake does not follow a linear continuum. Moreover, recent folate intervention trials raise concern about possible adverse effects of folate supplementation and suggest that too much folate in inopportune settings may be potentially harmful in individuals at higher risk for cardiovascular disease and cancer.
Although folate intake at sufficient levels appears to be an effective cancer chemopreventive strategy, high-dose supplementation of folate has generally not been effective in reducing recurrence of cardiovascular events or colorectal adenomas in clinical intervention trials. Although controversial, high folate status achieved through folate fortification or supplementation may increase the risk of certain chronic diseases among certain individuals, possibly by interfering with the homeostasis of one-carbon metabolism. Further research is urgently needed to accurately define the relationship between supraphysiological intake of folate and chronic diseases.

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    • "Epidemiological and clinical trials suggest that underground workers, particularly the coal miners, are under risk of severe health problems (Kado et al., 2002; Blom et al., 2011; Collin et al., 2010; Sauer et al., 2009). However, there are limited data on biochemical changes in underground workers . "
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    ABSTRACT: Aim: Several studies suggest that coal miners are under risk of severe health problems such as cardiovascular, pulmonary, neurological, renal, hematological and musculoskeletal disorders. However, there are limited data on biochemical changes in underground workers. In our study we aimed to evaluate the association between serum homocysteine (Hcy), vitamin B12, cystatin C and folate levels in the blood of underground coal miners. Materials and methods: Eighty one coal miners who work as underground or surface workers were recruited into our study. The study population was divided into two groups: the surface worker group (control group, n=33) and the underground worker group (n=48). The folate, vitamin B12, Hcy, cystatin C levels and body mass indexes (BMI) of both groups were measured and compared. Serum folate, Hcy and vitamin B12 levels were measured with a competitive chemiluminescence immunassay. Serum levels of cystatin C were determined by the latex particle-enhanced turbidimetric method using a cystatin C kit. Urea values were measured with a kinetic method on an automated analyzer. Results: There were no statistically significant differences between the underground workers and surface workers in the urea, cystatin C and vitamin B12 levels. High serum Hcy levels and low folate levels were found in underground workers compared with those in surface workers. The correlation between Hcy and folate levels was also statistically significant. Similarly, there was also a significant correlation between Hcy and vitamin B12, and between Hcy and cystatin C levels. Conclusions: Elevated Hcy levels may be associated with underground working but further research is necessary to understand the relation between elevated Hcy and increased prevalence of health problems in coal miners.
    Full-text · Article · Jul 2013 · Acta biochimica Polonica
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    • "Circulating folic acid must be metabolized by the tissues and the presence of unmetabolized folic acid could result in the accumulation of cellular dihydrofolate, an inhibitor of methylenetetrahydrofolate reductase [28] and thymidylate synthase [29]. Inhibition of these enzymes has been proposed to decrease methionine and thymidylate synthesis [30]. Consequently, high folic acid intake may, paradoxically, result in a functional folate deficiency, resulting in increased mutation rates and genome instability. "
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    ABSTRACT: To date, fewer than 50 mutagens have been studied for their ability to cause heritable mutations. The majority of those studied are classical mutagens like radiation and anti-cancer drugs. Very little is known about the dietary variables influencing germline mutation rates. Folate is essential for DNA synthesis and methylation and can impact chromatin structure. We therefore determined the effects of folic acid-deficient (0mg/kg), control (2mg/kg) and supplemented (6mg/kg) diets in early development and during lactation or post-weaning on mutation rates and chromatin quality in sperm of adult male Balb/c mice. The sperm chromatin structure assay and mutation frequencies at expanded simple tandem repeats (ESTRs) were used to evaluate germline DNA integrity. Treatment of a subset of mice fed the control diet with the mutagen ethylnitrosourea (ENU) at 8 weeks of age was included as a positive control. ENU treated mice exhibited decreased cauda sperm counts, increased DNA fragmentation and increased ESTR mutation frequencies relative to non-ENU treated mice fed the control diet. Male mice weaned to the folic acid deficient diet had decreased cauda sperm numbers, increased DNA fragmentation index, and increased ESTR mutation frequency. Folic acid deficiency in early development did not lead to changes in sperm counts or chromatin integrity in adult mice. Folic acid supplementation in early development or post-weaning did not affect germ cell measures. Therefore, adequate folic acid intake in adulthood is important for preventing chromatin damage and mutation in the male germline. Folic acid supplementation at the level achieved in this study does not improve nor is it detrimental to male germline chromatin integrity.
    Full-text · Article · Jul 2012 · Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
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    • "Therefore, folate has been implicated in colorectal cancer (CRC) because that the steps of folate metabolism may be involved in distinct biological process. A number of epidemiologic and experimental studies concluded that folate may have an inverse association with risk of CRC, however, the results are not consistent and it is argued that too much folate may be unfavourable for preventing the development of CRC especially in those with precursor lesions such as invisible minor adenoma (Giovannucci 2002; Sharp and Little 2004; Strohle, Wolters et al. 2005; Kim 2006; Sanderson, Stone et al. 2007; Sauer, Mason et al. 2009; Kennedy, Stern et al. 2011). The distinct effects of folate on the development of CRC in populations with diversely genetic background suggest that genetic factors, as well as the interaction with folate intake and other coenzymatical factors, may also play a role in the prevention or promotion of colorectal carcinogenesis (Giovannucci 2002; Sharp and Little 2004; Kim 2006; Arasaradnam, Commane et al. 2008; Hubner and Houlston 2009). "

    Full-text · Chapter · Feb 2012
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