Copper and cardiovascular health
Copper seems to be the schizophrenic metal, often thought of as very bad, and yet, very clearly recognized as necessary. Literally, a type of schizophrenia may be due to poor copper control and metabolism. (1) Copper has been recognized as an essential metal for a long time, since 1928. (2) The essential functions pertain to energy production, respiration, cardiovascular health, bones and joints, brain function, cholesterol metabolism, and hormone balance. (3-5)
Yet copper is often considered the cause, even for disorders it protects against, such as peroxidation of lipids, increased cholesterol, decreased HDL, and high LDL. (6-9) There has also been a general failure to recognize that copper deficiency is both common in America and a cause of many disorders. Such statements as “no evidence of copper deficiency” or “copper deficiency is rare” are usual. (10,11)
It is becoming increasingly important for health care providers to recognize the many-faceted role of copper in maintaining physical and mental health and longevity. The involvement of copper in the activity of many different metaloproteins is the reason it is an essential element. It is also the basis for copper deficiency being manifest in various disease states. It is increasingly important that copper deficiency be considered as a major problem and efforts be made to alleviate those disorders through dietary or supplement replacement. Some of the contributing factors to general deficiency include fertilizers and dietary factors such as excess fiber and phytates, iron, or zinc. (12-15)
Linder states that copper deficiency is not uncommon (as many imply). Also, research has shown the American diet to be deficient in copper. (16-18) A broad spectrum of physiology is affected by copper deficiency. Many persons experience problems due to that deficiency. In order to prevent or treat copper deficiency disorders, it is essential that the deficiency symptoms be recognized, and the deficiency be corrected by providing adequate copper in the diet. No other modality can cure or prevent the diseases caused by copper deficiency.
This paper will review the involvement of copper deficiency with respect to several critical conditions that affect cardiovascular health. (16-18) In a general sense, all metabolism eventually affects the cardiovascular system whether directly involved or not. We will consider here the more direct influences including cholesterol metabolism, vascular strength, blood pressure, heart rate, hemoglobin formation, iron transport, thyroid function, and peroxidation.
Other facets of copper metabolism that are not only critical to life and health, but also indirectly affect the heart or vascular system, include energy production, immune response, nervous activity, neuron structure, anti-inflammatory response, glucose metabolism, catecholamine formation, pigment formation, bone synthesis and stability, and joint function.
Much, if not most, of the medical world places the blame for cardiovascular disease on cholesterol. (19-23) This popularly publicized theory is responsible for focusing the blame on only one aspect of potential disease, and that is not entirely defensible. If we were to consider biochemical mechanisms more important than statistics, we might be better served with respect to prevention of cardiovascular incidents and the extension of life. However, since the cholesterol facade prevails, we might do well to consider the multifaceted involvement of copper in maintaining a healthy cholesterol level.
Thyroxine and Cholesterol
We begin our consideration with the thyroid gland function. In earlier times, it was recognized that a sluggish thyroid (hypothyroidism) was associated with hypercholesterolemia. In fact, in the days before all the modern diagnostic tests for thyroid function, physicians used cholesterol levels to judge thyroid activity. The relationship still exists. (18,24)
Consider the influence of copper on the production of thyroxin. Copper is involved in production of thyrotropin (thyroid stimulating hormone) by a protein kinase. Copper is necessary for the enzymes that form thyronine from tyrosine and is essential for the oxidation of iodine for formation of thyroxin from thyronine (iodine peroxidase, tyrosine iodinase, thyroid peroxidase, and many proteinases (names may vary; many papers in development). (25) Without adequate copper, the rate of production of thyroxine is impeded and thus cholesterol levels rise. (18)
One possible association is that thyroxine may inhibit the rate limiting enzyme in the production of cholesterol, hydroxymethyl glutaryl-CoA reductase. Thus, adequate thyroxine will limit cholesterol formation. (26) Therefore, we can correctly conclude that inadequate copper will lead to hypothyroidism which in turn produces hypercholesterolemia. (27)
A second consideration of the influence of copper on cholesterol levels is due to its role in cholesterol degradation and excretion. One means of control of cholesterol involves converting it into bile acids for excretion. This conversion is accomplished in the liver by a copper metalozyme: cholesterol-a-hydroxylase. A deficiency of copper impedes the enzyme, giving rise to hypercholesterolemia. The control of serum cholesterol is a complex biofeedback process.
Cholesterol is needed for normal metabolism, perhaps at least 1 g/day. (28) If it cannot be absorbed from the intestine, the liver will make it. Receptor cites for LDL cholesterol may control this activity. If excess is absorbed, more will be excreted in the bile. Attempting to prevent the synthesis and eliminating cholesterol from the diet may in fact upset the biofeedback system. Cholesterol-a-hydroxylase and hydroxymethyl glutaryl-CoA reductase working together with adequate copper and thyroxine would be expected to be the normal way to control cholesterol.
Some still relate elevated copper and hypercholesterolemia. However, recent research indicates there seems to be a contradiction in evidence presented. Having seen the controlling effects attributed to copper, we also have the research evidence that copper lowers overall cholesterol, increases HDL, and lowers LDL. (33-38)
There is still another concern. Most accept the concept that free radicals produce oxidized lipids that are responsible for plaque formation. (29) Copper is considered by many to be an oxidizing agent in the serum. Therefore copper is the culprit as a participant in atherogenesis. (30,31) Copper, in fact, becomes a part of a very important serum antioxidant, copper-zinc SOD. So perhaps, there are some overlooked mechanisms. A very important consideration is that copper levels in serum generally are associated with ceruloplasmin, albumin, other metaloproteins, and SOD. (32) SOD is perhaps the one of the most important antioxidants. These are mechanisms that control oxidation.
In efforts to study a disorder, there is a tendency to be locked into a single point of consideration. We know physiology does not work that way. Decrease in SOD activity due to copper deficiency promotes oxidation and free radicals. It is true then that insufficient copper will promote peroxidation. Sufficient copper does not cause it. (16-18)
There may be one other consideration in this regard. That is, control over the absorption of excess copper. (39) Some evidence indicates that metalothionines and some hormones, such as corticoids, may in fact control the absorption of copper. This would indicate that excess copper absorption is prevented much in the same way that excess iron absorption is controlled. (40-42) More research is needed. There may be much more physiologic control of the absorption of trace metals than we realize. This may be said with reference to the absorption of zinc, copper, iron, and perhaps even manganese and chromium. The active, dynamic energy requiring physiologic control of iron has been well studied, perhaps to the point of acceptance. (43-46)
Since there is some evidence that copper absorption and serum levels are controlled by corticosteroids, this may lay mute the argument of excess copper due to diet and rather turn toward poor utilization and increased demand on body stores for serum levels. Thus, other nutrients, such as bioflavin, ascorbic acid, and certain B vitamins, may be involved.
Copper and Homocysteine
Many researchers today consider that excess homocysteine due to inadequate excretion is the most likely cause of atherogenesis. (47) If homocysteine levels were adequately controlled, and adequate SOD were available, then the level of cholesterol would be of less consequence. The plaque buildup and the contribution of cholesterol and LDL may be much less significant if the arterial walls were not incompetent. Klevay has shown that low copper levels contribute to elevated homocysteine. (18)
Maintaining adequate hemoglobin is important for cardiovascular health since anemia will certainly cause more stress on the heart. Several copper metalozymes are involved in hemoglobin production. Succinyl-CoA and glycine through several steps requiring copper enzymes form d-aminolevulinic acid from which porphyrin is formed. Porphobilinogen is then formed and from it heme is produced. This process involves several synthase enzymes, transferase, and oxidase enzymes. (48)
Copper is essential for hemoglobin formation and the inclusion of iron in the heme molecule. The whole process of absorption of iron into the endothelial cells of the gut for storage, transfer to transferin in the serum, and storage in the liver or erytheropetic system involves several redox reactions which require copper. Iron is generally stored or utilized in the ferrous state but transported in the ferric state. It is for this reason that microcytic hypochromic anemia may be due to inadequate copper. (43-46)
Facilitates Oxygen Transport
An interesting note with regard to oxygen transport is that oxygen exchange (i.e., the uptake and release of oxygen by the iron in hemoglobin) requires the iron be in the ferrous state. Ferric ([Fe.sup.3+]) iron will not allow this exchange. If the hemoglobin were in an oxidizing milieu, oxygen exchange would not occur. The copper metalozymes are important in this regard.
Elastic tissue formation and repair is critical to cardiovascular health. The arterial walls are made up of elastin in order to have strength and flexibility. Elastin is made from the amino acid lysine, by the enzyme lysil oxidase. The enzyme, which needs copper as a co-factor, deaminates four molecules of lysine and cross-links them to form desmosine, which is further cross-linked to form elastin. (49)
If there is a copper deficiency, the action of lysyl oxydase in the production of elastin will be impeded, and there will be a greater disposition to aortic aneurysms and perhaps vericosities.
Hypertension, which can critically affect the cardiovascular system, may involve copper. (4,50,51) Hypertension, one of the leading causes of death, can lead to stroke, aneurysms, and heart failure. Many who experience idiopathic hypertension may also have inadequate copper levels. There may be several associations with effects of copper deficiency on the vascular system with hypertension, such as loss of elasticity and atherogenesis. Copper may also have a hypertensive effect due to involvement with hormone production. It is possible, even feasible, that many who suffer idiopathic hypertension have copper deficiency. That opens the possibility of treating many with idiopathic hypertension with a simple copper supplement.
Research indicates that the American diet is deficient in copper. A deficiency in copper affects the cardiovascular system in several negative ways. Cardiovascular disease is a leading cause of death in America. It seems to be quite logical that dietary improvement or copper supplements be considered appropriate for preventing copper deficiency disorders which manifest as disorders of the cardiovascular system that lead to death. It also seems to be more appropriate to correct the primary cause of a potential disorder than to treat the symptomatic manifestation with questionable metabolic altering medication. A simple trace metal test for copper in the hair (52-54) will usually indicate the deficiency, showing the need for more copper in the diet. A small copper supplement may be the way not only to save many lives but also to improve the quality of life. (55)
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by C. R. Puckett, MS
About the Author
C. R., Puckett, MS, received his master’s degree in the field of chemistry from Abilene Christian University and did additional studies at the University of New Mexico. He has taught chemistry and biology at Abilene Christian, Oklahoma Christian University, and South Plains College. He did clinical research at Lovelace Foundation and served as the Clinical Chemist at a Veteran’s Administration hospital for 16 years before establishing a laboratory to do trace metal analysis for alternative physicians. He has presented nutrition and trace metal metabolism seminars for chiropractic and integrative medicine groups for more than 27 years. He is the president and technical director of Biochemical Laboratories.
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