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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:e160.)
© 2008 American Heart Association, Inc.

Letters to the Editor

Homocysteine Is Not So Paradoxical

Leslie M. Klevay

Departments of Internal Medicine, and of, Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota, School of Medicine and Health Sciences

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

Rodionov and Lentz¹ summarized the homocysteine paradox. Hyperhomocysteinemia disrupts vascular structure and function in animals and predicts risk of "coronary events, stroke, venous thromboembolism, and death," yet clinical benefit in intervention trials remains unproved. They offer several plausible explanations.

Trials usually involve dietary supplementation with folate and vitamins B-6 and B-12. It also seems plausible that results would have been better if the intervention trials included copper.

High homocysteine concentrations lead to increased homocysteine thiolactone,² an irreversible inhibitor of lysyl oxidase³ which depends on copper to initiate the cross-linking of collagen and elastin in arteries.⁴ Insufficient lysyl oxidase leads to vascular disease.⁴ Thus decreasing homocysteine may not lead to vascular repair without extra copper which also can lower plasma homocysteine.⁵

The Western diet is often low in copper⁶ according to pooled data from several articles on more than 900 adult diets chemically analyzed. Sixty-two percent and 36% of diets of 80 randomly selected adults in Baltimore⁷ were below the recommended dietary allowance and the estimated average requirement for adults, 0.9 and 0.7 mg daily, respectively.⁸ Diets low in copper tend to be low in folate as well and vice versa.⁹

Copper deficiency is the only nutritional insult that elevates cholesterol, blood pressure, homocysteine, isoprostanes, and uric acid, has adverse effects on electrocardiograms and arteries, impairs glucose tolerance and paraoxonase activity, and promotes thrombosis and oxidative damage. More than 80 anatomic, chemical, and physiological similarities between animals deficient in copper and people with ischemic heart disease have been . . . [Full Text of this Article]