Dietary copper and risk of coronary heart disease

US Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, PO Box 9034 Grand Forks, ND 58202-9034

Dear Sir:

Liu et al (1) found that "higher intakes of whole-grain foods were associated with lower risks of both fatal and nonfatal" coronary heart disease among thousands of women studied since 1984. The association was not fully explained by the contribution of whole grains to intakes of dietary fiber, folate, or vitamins B-6 and E. The authors suggested the possibility of "additional protective effects of other constituents." An accompanying editorial (2) mentioned more than a baker's dozen of possibly protective constituents concentrated in whole grains, including copper.

That copper nutriture may affect risk of coronary heart disease first was suggested in the Journal in 1973 (3). The original hypothesis (4) was modified and has evolved into the copper deficiency theory (5, 6) of the etiology and pathophysiology of ischemic heart disease because of numerous, consonant experiments in animals and people. In brief, the Western diet is frequently low in copper. Copper deficiency is the only nutritional insult that elevates cholesterol (7), blood pressure (8), and uric acid; has adverse effects on electrocardiograms (7, 9); impairs glucose tolerance (10), to which males respond differently than do females; and which promotes thrombosis and oxidative damage. More than 75 anatomic, chemical, and physiologic similarities between animals deficient in copper and people with ischemic heart disease have been identified. Copper deficiency is offered as the simplest and most general explanation for ischemic heart disease.

One wonders whether comparison of higher with lower quintiles of whole-grain intake (1) would show higher amounts of copper in the former. Such a result would be compatible with the positive correlation between coronary artery health at angiogram and leukocyte copper (11); a higher leukocyte copper concentration in Japanese people in Okinawa, where the prevalence of heart disease is lower than in Japanese people in Brazil (12); a positive correlation between cardiac output and cardiac copper in patients with coronary heart disease (13); and lower superoxide dismutase activity in angiogram patients with a history of myocardial infarction than in similar patients without such a history (14).

REFERENCES

1. Liu SM, Stampfer MJ, Hu FB, et al. Whole-grain consumption and risk of coronary heart disease: results from the Nurses' Health Study. Am J Clin Nutr 1999;70:412–9.
2. Anderson JW, Hanna TJ. Whole grains and protection against coronary heart disease: what are the active components and mechanisms? Am J Clin Nutr 1999;70:307–8.
3. Klevay LM. Hypercholesterolemia in rats produced by an increase in the ratio of zinc to copper ingested. Am J Clin Nutr 1973; 26:1060–8.
4. Klevay LM. Coronary heart disease: the zinc/copper hypothesis. Am J Clin Nutr 1975;28:764–74.
5. Copper bioavailability and metabolism. Adv Exp Med Biol 1989;258:1–302.
6. Klevay LM. Trace element and mineral nutrition in disease: ischemic heart disease. In: Bogden JD, Klevay LM, eds. Clinical nutrition of the essential trace elements and minerals: the guide for health professionals. 1st ed. Totowa, NJ: The Humana Press Inc (in press).
7. Klevay LM, Inman L, Johnson LK, et al. Increased cholesterol in plasma in a young man during experimental copper depletion. Metabolism 1984;33:1112–8.
8. Lukaski HC, Klevay LM, Milne DB. Effects of dietary copper on human autonomic cardiovascular function. Eur J Appl Physiol 1988; 58:74–80.
9. Reiser S, Smith JC Jr, Mertz W, et al. Indices of copper status in humans consuming a typical American diet containing either fructose or starch. Am J Clin Nutr 1985;42:242–51.
10. Klevay LM, Canfield WK, Gallagher SK, et al. Decreased glucose tolerance in two men during experimental copper depletion. Nutr Rep Int 1986;33:371–82.
11. Kinsman GD, Howard AN, Stone DL, Mullins PA. Studies in copper status and atherosclerosis. Biochem Soc Trans 1990;18:1186–8.
12. Mielcarz GW, Howard AN, Williams NR, et al. Copper and zinc status as a risk factor for ischemic heart disease: a comparison between Japanese in Brazil and Okinawa. J Trace Elem Exp Med 1997; 10:29–35.
13. Oster O, Dahm M, Oelert H. Element concentrations (selenium, copper, zinc, iron, magnesium, potassium, phosphorous) in heart tissue of patients with coronary heart disease correlated with physiological parameters of the heart. Eur Heart J 1993;14:770–4.
14. Wang XL, Adachi T, Sim AS, Wilcken DE. Plasma extracellular superoxide dismutase levels in an Australian population with coronary artery disease. Arterioscler Thromb Vasc Biol 1998;18:1915–21.