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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

ABSTRACT 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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Available from: Joel B Mason, Aug 30, 2015
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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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    Acta biochimica Polonica 07/2013; · 1.39 Impact Factor
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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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    • "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). "
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