Ischemic heart disease, the leading cause of death in the United States, became increasingly common during the 20th century. Its etiology remains obscure. Increased serum cholesterol predicts cardiovascular risk, and thousands of medical articles have described the effects of dietary fat on cholesterol metabolism. However, more than 50 studies of various populations have failed to associate fat intake with risk. Other characteristics predictive of cardiovascular risk include electrocardiographic abnormalities, glucose intolerance, and high blood pressure. Uric acid is so closely associated with risk that the Framingham multivariate analyses corrected for uric acid levels.
However, if the incidence of a disease, in this case heart disease, changes over time, one might expect similar changes in the suspected causal agents. Dietary fat has not changed in the US for a century. In contrast, dietary copper has decreased since the 1930s.
Deficiency diseases, such as beriberi, pellagra, and scurvy, have nearly disappeared in the US. Inspired by the now well-known protective effect of hard drinking water on heart disease, I began to study trace elements and discovered fifty years ago that rats deficient in copper have very high cholesterol levels. This discovery prompted a search for characteristics of animals deficient in copper and relationships between copper metabolism and heart disease. Feeding cholesterol to animals also has produced similarities to heart disease because cholesterol feeding induces copper deficiency.
Recently, more than 30 men and women have been depleted of copper with care. Some people had abnormal blood pressure responses, abnormal heartbeats, high cholesterol, and glucose intolerance. One of the experiments was modified because some men experienced severe tachycardias, heart block, and a heart attack.
At least 80 anatomical, chemical, and physiological similarities exist between people with ischemic heart disease and animals deficient in copper. Coronary artery thrombosis, decreased cardiac copper, hyperuricemia, heart blocks, glucose intolerance, and myocardial infarction are among the more important. Recently, paraoxonase was found decreased in copper deficiency. This enzyme destroys homocysteine thiolactone, which inhibits an enzyme required for the synthesis and repair of arterial connective tissue.
Sugar-sweetened beverages and soft drinks have also been associated with increased heart disease risk. Two-thirds of sugary beverages likely contain “soft” water [1] without copper. While sugars, especially fructose, interfere with copper metabolism in animals, the use of “hard” water in beer and wine may contribute to the protective effect of alcoholic beverages on heart disease risk.
Identifying individuals with low levels of copper can be difficult; serum copper is increased by inflammation, and recent research suggests that serum copper should be corrected for the degree of inflammation present. Newer tests, such as enzyme activity of superoxide dismutase in red blood cells, should be used more widely. This enzyme defends against oxidative stress.
Our daily copper requirements must be determined by depletion studies. For copper, this amount is 0.7mg/day; the recommended dietary allowance (RDA) is 0.9mg/day. Diets with less copper than the RDA for copper are typical. It is unknown if men have a different copper requirement than women.
The copper deficiency theory on the etiology and pathophysiology of ischemic heart disease is the simplest and most general theory on the etiology and pathophysiology of ischemic heart disease that has been proposed because it encompasses the observations of Barker concerning small babies, McCully concerning homocysteine, and Sullivan concerning iron overload.
- Small babies often are born before maternal metabolism supplements them with copper, and small birth weight is associated with heart disease in middle age.
- High levels of homocysteine are associated with injury to the coronary arteries; Copper supplementation lowered plasma homocysteine in men.
- Loss of iron through menstruation may protect women from heart disease. Excess iron can interfere with copper utilization. Iron supplements may well require additional copper.
Tests of this theory need not involve hundreds of patients, as is the case with many current therapeutic studies on heart disease. A small study of septuagenarian patients with chronic heart failure and ischemic heart disease showed that a supplement containing copper improved left ventricular function and quality of life over ten months. More research on copper may lead to the disappearance of ischemic heart disease.
[1] Hard water contains high concentrations of calcium and magnesium. Water softeners replace these elements with sodium.
