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Methoxistasis: Integrating the Roles of Homocysteine and Folic Acid in Cardiovascular Pathobiology
Department of Medicine, VA Boston Healthcare System, Boston, MA 02132, USA
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA
* Author to whom correspondence should be addressed.
Received: 6 May 2013; in revised form: 22 July 2013 / Accepted: 1 August 2013 / Published: 15 August 2013
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
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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.
Joseph J, Loscalzo J. Methoxistasis: Integrating the Roles of Homocysteine and Folic Acid in Cardiovascular Pathobiology. Nutrients. 2013; 5(8):3235-3256.
Joseph, Jacob; Loscalzo, Joseph. 2013. "Methoxistasis: Integrating the Roles of Homocysteine and Folic Acid in Cardiovascular Pathobiology." Nutrients 5, no. 8: 3235-3256.