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Somewhat surprising, most of the research looking at the correlation between hyperhomocysteinemia and a wide range of diseases—cardiovascular disease (eg, atherosclerosis and thrombosis), autoimmune disease (eg, type 1 and type 2 diabetes), gastrointestinal disorders (eg, constipation, inflammatory bowel disease, Crohn’s disease, and colorectal cancer), bone density, and neurodegenerative disease (eg, Alzheimer’s disease, depression, and Parkinson’s disease)—actually find significantly stronger associations with aberrant methylation and folate metabolism abnormalities.5 This seems to substantiate the perspective that although homocysteine is directly toxic, more important is that hyperhomocysteinemia is a marker of metabolic dysfunction, primarily methylation disruption
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