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Nutrients 2013, 5(8), 3235-3256; doi:10.3390/nu5083235
Review

Methoxistasis: Integrating the Roles of Homocysteine and Folic Acid in Cardiovascular Pathobiology

1,2,*  and 2
Received: 6 May 2013; in revised form: 22 July 2013 / Accepted: 1 August 2013 / Published: 15 August 2013
(This article belongs to the Special Issue Folate Metabolism and Nutrition)
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Abstract: Over the last four decades, abnormalities in the methionine-homocysteine cycle and associated folate metabolism have garnered great interest due to the reported link between hyperhomocysteinemia and human pathology, especially atherothrombotic cardiovascular disease. However, clinical trials of B-vitamin supplementation including high doses of folic acid have not demonstrated any benefit in preventing or treating cardiovascular disease. In addition to the fact that these clinical trials may have been shorter in duration than appropriate for modulating chronic disease states, it is likely that reduction of the blood homocysteine level may be an oversimplified approach to a complex biologic perturbation. The methionine-homocysteine cycle and folate metabolism regulate redox and methylation reactions and are, in turn, regulated by redox and methylation status. Under normal conditions, a normal redox-methylation balance, or “methoxistasis”, exists, coordinated by the methionine-homocysteine cycle. An abnormal homocysteine level seen in pathologic states may reflect a disturbance of methoxistasis. We propose that future research should be targeted at estimating the deviation from methoxistasis and how best to restore it. This approach could lead to significant advances in preventing and treating cardiovascular diseases, including heart failure.
Keywords: methionine; homocysteine; folic acid; cardiovascular disease; heart failure; nutrition; pyridoxine; cobalamin; nutrition; redox; methylation methionine; homocysteine; folic acid; cardiovascular disease; heart failure; nutrition; pyridoxine; cobalamin; nutrition; redox; methylation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Joseph, J.; Loscalzo, J. Methoxistasis: Integrating the Roles of Homocysteine and Folic Acid in Cardiovascular Pathobiology. Nutrients 2013, 5, 3235-3256.

AMA Style

Joseph J, Loscalzo J. Methoxistasis: Integrating the Roles of Homocysteine and Folic Acid in Cardiovascular Pathobiology. Nutrients. 2013; 5(8):3235-3256.

Chicago/Turabian Style

Joseph, Jacob; Loscalzo, Joseph. 2013. "Methoxistasis: Integrating the Roles of Homocysteine and Folic Acid in Cardiovascular Pathobiology." Nutrients 5, no. 8: 3235-3256.



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