Medline Articles in the treatment of Disease

Trace elements Argument in rheumatic conditions.

Trace elements in the treatment of rheumatic conditions.

Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older.

Daily oral magnesium supplementation suppresses bone turnover in young adult males.

Low vitamin D levels increase risk for osteoarthritis.

Arthritis sufferers need more B-6, zinc, magnesium, copper and folic acid.

Boron is essential for healthy bones and joints.

Arthritis sufferers may benefit from selenium supplementation.

Arthritis sufferers may need more vitamin B-6, zinc and magnesium.

Copper, manganese and zinc help preserve bone.

Boron supplementation prevents calcium loss and bone demineralization.

Copper may be an effective anti-inflammatory.

Zinc helps to preserve bone.

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1: Rheum Dis Clin North Am 1999 Nov;25(4):929-35, viii Related Articles, Books, LinkOut

Trace elements in the treatment of rheumatic conditions.

Rosenstein ED, Caldwell JR.

Arthritis and Rheumatic Disease Center, Saint Barnabas Medical Center, Livingston, New Jersey, USA.

The role of trace metallic elements (copper, selenium, zinc, gold) in chronic inflammatory states is of great interest because many of them are co-factors in metabolic processes involving articular tissues and immune system function. Deficiencies of several of these have been documented in patients with rheumatoid arthritis. Other than for the clinically approved gold compounds, there exists only inconsistent evidence for a therapeutic role of trace metallic elements in the management of rheumatoid arthritis.

Publication Types:

Review
Review, tutorial

PMID: 10573767 [PubMed - indexed for MEDLINE]

Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older.

Dawson-Hughes B, Harris SS, Krall EA, Dallal GE.

Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.

BACKGROUND: Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons. METHODS: We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density, biochemical measures of bone metabolism, and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home. They received either 500 mg of calcium plus 700 IU of vitamin D3 (cholecalciferol) per day or placebo. Bone mineral density was measured by dual-energy x-ray absorptiometry, blood and urine were analyzed every six months, and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records. RESULTS: The mean (+/-SD) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows: femoral neck, +0.50+/-4.80 and -0.70+/-5.03 percent, respectively (P=0.02); spine,+2.12+/-4.06 and +1.22+/-4.25 percent (P=0.04); and total body, +0.06+/-1.83 and -1.09+/-1.71 percent (P<0.001). The difference between the calcium-vitamin D and placebo groups was significant at all skeletal sites after one year, but it was significant only for total-body bone mineral density in the second and third years. Of 37 subjects who had nonvertebral fractures, 26 were in the placebo group and 11 were in the calcium-vitamin D group (P=0.02). CONCLUSIONS: In men and women 65 years of age or older who are living in the community, dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck, spine, and total body over the three-year study period and reduced the incidence of nonvertebral fractures.

Publication Types:

· Clinical trial

· Randomized controlled trial

PMID: 9278463 [PubMed - indexed for MEDLINE]

J Clin Endocrinol Metab 1998 Aug;83(8):2742-8

COPPER RESPONSE IN ARTHRITIS

I have come to believe that the disturbance of copper metabolism is the most serious symptom of arthritis. The aspect of copper physiology which is most potentially dangerous is its role in activating lysyl oxidase, the enzyme which cross links collagen and elastin connecting tissue.1 Copper’s effect on elastin is especially important because elastin gains its strength primarily from cross linking and because elastin is the main material of several important organs.

Overall Copper Physiology

Copper, largely tied up as protein, enters the stomach, and there and in the upper intestine, the proteins other than those entering from the bile are degraded (bile proteins are degraded in infant animals when cortisol is low), thus making the bile the means of excretion for adults. The copper is moved across cell walls possibly associated with certain amino acids. The copper moves past a metallothionein barrier inside the cells into the serum, which carries it largely complexed to albumin, to the liver. The liver rapidly removes it and stores it until such time as unknown hormones (which probably don’t include cortisol in any direct way, but may include ACTH) cause the liver to release ceruloplasmin which contains copper for general purposes, as well as free copper when under stress. The ceruloplasmin transporter is destroyed by the target cells including those which make bile proteins for copper excretion. In case of infection, decline of the effect of cortisol and corticosterone (not necessarily concentration itself) shut down unnecessary copper enzymes in order to provide increased copper to the immune system. In case of a potassium wasting intestinal disease, both DOC and cortisol are used for this purpose. If these hormones shut down copper enzymes permanently by an ongoing potassium deficiency, health is degraded. The most serious effects are weakening of the elastin tissue derived arteries by inhibition of the lysyl oxidase system, along with fatty buildup in the arteries. Increased excretion in the presence of marginal copper intake can lower liver stores of copper sufficiently that the immune system can not operate effectively. These two effects, along with heart failure account for most of the mortality of rheumatoid arthritis.

Elastin Connecting Tissue

Elastin makes up the vertebrate disks above the sacroiliac, the blood vessels, much of the skin, the lungs, and the bronchial tubes 2 of all vertebrates except the jawless fishes.3 The blood vessels are the most important because an organism can not remain alive after a large blood vessel bursts. Ruptured blood vessels are second after heart failure in deaths among arthritic people.4 Tough disks are fairly important also, because of their role in guarding the main nerve trunk. Lungs and bronchial tubes are not subject to such extreme stress. However, emphysema can be produced in animals by a copper deficiency, and it is possible that an association will be uncovered in arthritic people, especially men, old women, or young women after a pregnancy. There is no current evidence that hemorrhoids are made worse by a copper deficiency, but limited experience leads me to believe that evidence will one day appear. I also suspect that a tendency to cut oneself while shaving will prove to be correlated. If so, this would serve as a good early warning.

Numerous animal experiments have shown that a copper deficiency can cause diseases affected by elastin tissue strength. Aneurysms of the aorta are the chief cause of death of deficient chickens.5 Emphysema in the absence of smoking has been produced in pigs. The defect is said to be greater than can be explained by weakened elastin alone.6 Dilated superficial veins (varicose veins) are observed in copper deficient organisms.7 Men who die of aneurysms invariably have a low liver content.8 Tissue copper is also low. Men are more susceptible to aneurysms than young women, probably because estrogen increases the efficiency of absorption. However, women can be affected by some of these problems after pregnancy, probably because women must give the liver of their babies large copper stores in order to survive the low milk copper.

Copper Enzymes

Other enzymes than lysyl oxidase require copper to activate them. One is undoubtedly a mechanism behind anemia.9 Tyrosinase incorporates tyrosine into melanin pigment and is the reason why copper deficient sheep fail to pigment.10 It is conceivable that human gray hair is also arrives this way. Low white blood cell count (neutropenia) is the earliest symptom in copper deficient babies.11 The immune system is very sensitive to adequate copper.12 The mechanism has not been elucidated. It is likely that several enzymes are involved, and white blood cells are rich in copper.13 White cell count rises in affected babies within 2 or 3 days after supplement with 2 or 3 mg of copper per day. Supplements or copper rich foods should be used for babies with extreme care, as should be formula made from water out of copper plumbing or brass pots, because babies can not excrete copper. Several brain neurotransmitters such as dopamine 15 and norepinephrine 16 are formed by copper enzymes. It is possible that this is part of the poor muscle tone and motor response sometimes observed in a deficiency.17 A copper deficit causes impairment of glucose tolerance.18 Both insulin and extra copper during a deficit increase fat deposition, 19 but both together have a synergistic effect greater than either one alone.19 There must be a copper catalyzed enzyme somewhere in the process, therefore. One investigator has suggested that buildup of copper in the kidneys of diabetics is responsible for the kidney damage which sometimes appears in diabetics 20. Diabetics absorb copper more readily than normals.21 Diabetics may have a narrow safe range of intake.

Recurrent diarrhea is often observed in a copper deficit.22 This may be related to the known sensitivity of the immune system to copper. Scurvy like bone changes are a long term result, probably caused by failure of bone collagen to cross link.23 It is very unlikely that this can be corrected by future intake because of low bone turnover, so adequate intake is crucial for older babies. The age at which human babies stop degrading bile copper protein is unknown to me, although it probably happens gradually. Collagen does turnover, but very slowly. Bone collagen is so slow that correct intake in childhood is essential. Elastin probably has a high turnover 24 and also may be porous to the enzyme. I feel that improvement in less than a week is reasonable to expect for elastin tissue. This is fortunate in view of the extreme danger of elastin ruptures.

A copper deficiency has the characteristic of increasing cholesterol in the blood stream.25 It has been suggested that a high zinc to copper intake ratio is an important part of this.26 The rise in cholesterol and triglycerides has been attributed to a 40% or more reduction in lipoprotein lipase.27 I do not know whether this is a copper enzyme or not. This may be an adaptation to provide extra cholesterol for lining the arteries with deposits in order to help protect them against rupture by decreasing their internal diameter. Whatever the evolutionary stimulus, copper deficiency is a much more plausible explanation of high serum cholesterol than any difference in cholesterol intake, since the body can synthesize its own cholesterol and average cholesterol intake has not varied more than 5% in the last 100 years.28 No enzyme system has been linked to this phenomenon yet to my knowledge, and, indeed it is more likely to be controlled by hormones in some manner. Non ceruloplasmin copper is said to signal the increase.29

Potassium Deficiency

Some of these symptoms also appear in arthritic people. I believe I now see how potassium deficiency may be disturbing metabolism in order to produce them. Potassium wasting infectious disease is the only likely reason for a severe potassium deficiency in nature, not nutritional failure. I propose that the body uses the electrolyte hormone system to stimulate part of the immune system and to alter the basic physiology in order to mobilize the body’s defenses against a lethal intestinal disease. Infections of the intestinal tract should be difficult to detect, and the diarrheas, including cholera, may be examples of the type of potassium wasting diseases which forced this system to evolve. Even in the modern world diarrhea is a major cause of death in children, especially in the tropics.

Resisting infection is an extremely important function of the body. It is even related to predation because a diseased animal has great difficulty escaping. It is therefore plausible, as I am about to propose, that numerous physiological processes are fundamentally altered in order to more effectively fight off infection, in the above case, diarrhea.

Cross Linking Connective Tissue

The immune system is considerably weakened by inadequate copper as mentioned above. It is therefore logical for the body to attempt to increase the copper available to the white blood cells during disease. It would also be desirable to signal this increase using a hormone system which does it by declining. Otherwise a pathogen could evolve which could consistently overwhelm the immune system simply by making an enzyme which destroyed the hormones. Shutting down enzyme systems which were not immediately essential to immunity is one way to increase availability of copper.

11 Deoxycorticosterone (DOC) is a hormone probably used by the body to regulate sodium and potassium when intake of both of them is high.30 It declines during a deficiency of both potassium and sodium.31 It also stimulates lysyl oxidase activity 32 which we have previously mentioned as responsible for cross linking all connecting tissue. This is not a serious compromise for a short time compared to the monumental importance of defeating an infection. However if there is an inappropriate potassium deficiency which goes on for years, connecting tissue can be badly weakened. The effect is probably accentuated by low sodium.

The effects of muted cross linking are especially serious for elastin tissue because the disordered rubbery organization depends entirely on the cross linking for strength. Lysyl oxidase oxidizes the amino group in lysine 33 which amino acid is common in elastin. The aldehyde which forms spontaneously combines with adjacent amine and aldehyde groups to form strong covalent bonds and thus join together the fairly small protein precursor molecules. The same thing happens for collagen, but collagen has many less cross links, probably made possible by collagen’s greater length and more ordered structure which permits numerous weak hydrogen bonds to be effective. The strength of chick tendon is little affected by copper deficiency, even though the animals are dying of ruptured aortas.34 The lesser number of cross links are desirable, for they permit the tendons to return to their original position after stress is relieved and not to cold flow as polymers held together only by hydrogen bonds do. The number of cross links are probably optimum, because too many would make the tendon brittle. Too few cross links would cause the tendon to become slack with time. Thus the body has a tough material which approaches steel in strength weight for weight and bones which are almost as strong as cast iron. The lesser reliance by collagen on cross linking for strength may be the reason why the body uses collagen to repair lesions in arteries during a deficiency instead of elastin.35 Such a strategy may be a good immediate expedient for survival, but I suspect it results in an intractable hypertension eventually because collagen is less rubbery or elastic than elastin.

Superoxide

It has been proposed that the immune system generates superoxide in order to help kill bacteria.36 Normally the copper catalyzed superoxide dismutase enzyme destroys superoxide radicals as fast as they form. This enzyme declines during infection.37 Thus there would be a double advantage in diverting copper from this enzyme. I do not know yet whether decline of this enzyme is tied to the potassium hormone system or not. Superoxide degrades the joint fluids 38 and possibly collagen as well as bacteria. I suspect that this is an unavoidable compromise, tolerated because of the extreme urgency of fighting disease. Decline of this enzyme has been proposed as one of the mechanisms accounting for some of the symptoms of rheumatoid arthritis,39 which is an indication that this enzyme is indeed tied to the potassium enzyme systems.

Glucocorticoids

I propose that the primary purpose of glucocorticoids (steroids oxygenated in the 17 carbon position) is to mobilize the body to resist infection. They do so by normally altering processes which increase pathogens’ growth or adverse effects and then declining when under attack. As already mentioned this inverse style is much safer for resisting infection. I propose that cortisol is for intestinal disease and corticosterone for serum disease. Glucocorticoid mobilization for fight or flight is an adjunct made possible because most processes which resist infection are an antithesis for fight or flight.40 Release of ceruloplasmin copper transport protein from the liver is useful for both situations and is therefore controlled by a different hormone, epinephrine, for fight or flight.41 Potassium loss is the most serious aspect of intestinal diseases, so the electrolyte capabilities of cortisol, but not corticosterone, are oriented around conserving potassium by migration into the cells upon decline of cortisol.42 Cortisol, but not corticosterone, has its secretion from the adrenal cortex markedly reduced by low serum potassium (in vitro, that is test tube, experiments).43 Sodium, water, glucose, amino acids, chloride, hydrogen ion, white blood cell activity, copper enzymes, and numerous other hormones and enzymes are controlled by cortisol such as to survive during virulent intestinal disease.40 Cortisol works by declining effect, not necessarily declining concentration. Indeed, in most diseases glucocorticoids actually rise. However, at the same time T white blood cells secrete a protein, gluco-corticosteroid response modifying factor (GRMF), and the protein hormone interleuken-1 both of which inhibit the effect of cortisol on white blood cells other than the suppressor cells.44 The effect of GRMF on physiological processes is unknown at present. The husband and wife team working on GRMF were almost murdered and this disrupted current investigations. I suspect that most of cortisol’s effects on copper enzymes will prove to be involved with GRMFs. These two protein factors thus raise the effective set point of cortisol. This system also uses interleukin-1 to stimulate the production of ACTH, and thereby also cortisol, instead of the brain’s corticosteroid releasing factor (CRF) which last is used in the absence of infection. The immune cells thus take over their own regulation.

Cortisol

Cortisol, like DOC, also stimulates lysyl oxidase activity,45 and undoubtedly for the same reason, that is to provide extra copper to white blood cells during infection upon decline. Its action on collagen is exactly the opposite of DOC’s:46 cortisol inhibits collagen formation.47 This is significant because collagen is the most bulk of protein, is inert, and makes relatively non vital structures. This attribute of cortisol would be a desirable attribute if the pathogen were in the serum, because increased synthesis of collagen when cortisol declined would considerably lower free amino acids in the blood stream, and thus slow down bacterial growth. There would be little advantage from this during diarrhea, and this may be why DOC acts in the opposite direction and thus counteracts cortisol’s effect when diarrhea is involved. I submit that potassium would be a lot safer way of increasing cortisol than use of injections. Steroids are hormones, not pharmaceuticals. Their sole purpose is to keep important body functions and concentrations at values optimum for survival. There should be no reason why artificial additions should be necessary under normal conditions and adequate nutrition for anyone free of genetic defects. Quite often a steroid is injected with impunity and seemingly no immediate obvious adverse symptoms. But this is usually because other hormones alter in an attempt to adjust the imbalance and because many of the adverse symptoms such as, for instance, negative feedback which causes reduction in secretory cells of the hormone is a long time in materializing. One medical writer summed it up so: “it is remarkable how effective cortisol is in getting a seemingly hopeless patient on his feet again. Sometimes it is so effective, he can walk all the way to the autopsy table”.

Ceruloplasmin

Ceruloplasmin is higher than normal in the blood serum of arthritic people.49 Ceruloplasmin is almost certainly used as a transport protein to bring copper from the liver to the target cells50 in addition to its other transport uses. Ceruloplasmin is a blood protein which contains 6 51 or 8 52 atoms of copper inside the molecule which are not in equilibrium with the serum.53 Such a transport mechanism would be extremely useful in case of infection, because ceruloplasmin’s copper is not in equilibrium with the serum, and is thus not available to pathogens.55 One of its copper atoms may be exchangeable under reducing (anaerobic) conditions,56 however. The hormone system which regulates creation of ceruloplasmin by the liver is unknown to me. Cortisol is not directly part of it, although ACTH which regulates cortisol may be.57 Cortisol does stimulate the formation of metallothionein, the copper storage protein.58 Thus copper should become more available for ceruloplasmin synthesis inside the liver upon decline of cortisol.

The mortality of chicks from salmonella infections rises significantly from zero if large amounts of copper as copper sulfate is fed, which supports the contention that this is the reason why the body increases ceruloplasmin greatly during infection59 but not equilibrium copper bound to albumin and histadine.60 This concept is reinforced by the fact that chicks in the absence of infection have a very low ceruloplasmin serum content.61 The fact that people with Wilson’s disease are not susceptible to infection even though they cannot synthesize ceruloplasmin does not refute ceruloplasmin’s role proposed above. This is because people with Wilson’s disease can not excrete copper so that their cells are already loaded and even overloaded with copper. The high ceruloplasmin content of mammals may originally have been an adaptation from their immune use to supply extra copper to the embryo by females. Even today human females have a higher ceruloplasmin content than males do.62 There may be a similar advantage keeping free copper from funguses as well, if a limited experiment I tried is an indication. Bacteria could not make use of the copper in ceruloplasmin unless they were to evolve an elaborate mechanism for preferentially binding the ceruloplasmin and then degrading it. This would be an unlikely occurrence.

It is possible then, that the best way to relieve a copper deficiency which is concurrent with a bacterial infection would be by ceruloplasmin injections. Such a procedure would bear investigation in view of the unlikely possibility that people will change their diets and eat enough copper or delete copper physiology poisons which may include tobacco. White blood cell count is very sensitive to copper status. A copper deficiency makes it impossible for an animal to increase the size of the spleen during an infection.63 Such animals took an average of one third as long a time to die as replete animals, and had four times the mortality.64 I believe that the efficacy of adequate copper prior to an infection is established beyond any reasonable doubt. Dietary copper DURING an infection may be disadvantageous, except during a deficiency, when it probably would be best to spread it out across the day complexed to protein. A depleted liver removes free copper from the blood with extreme rapidity,65 however, so the danger is probably not acute.

Since ceruloplasmin is probably used to transport copper to the bile for excretion, excretion may inadvertently rise when ceruloplasmin rises during infection. A similar mechanism may account for the higher ceruloplasmin content in the serum of arthritic people.66 Apparently decline of cortisol is not used for this purpose and the hormones which do are unknown. ACTH can not be used for this because its effect is direct.67 There could be an increased excretion arising from the higher serum content of arthritic people. If this is so, arthritic people may need somewhat more copper than others until their potassium deficiency is relieved. This may be why their liver copper is low, why their whole blood copper does not rise even though the serum is high, and part of the reason why they are much more likely to die from ruptured blood vessels and infection than others.68 Thus rheumatoid arthritis could be viewed as often a multiple deficiency, not all of the symptoms of which can be always removed by supplying only one of them.

Arthritic people also have a higher free copper content in their blood serum.69 This would seem at first glance to be at variance with the concept that arthritis is an inappropriate immune response. However, intestinal diseases should not be affected much by free copper in the serum, so that immune copper responses accentuated by potassium deficiency may have some subtle differences from responses which are involved primarily with serum infections. Free copper may be more useful to an animal when muscle exertion is needed, because when sheep which have been subjected to a copper toxicity hear the bark of a dog, so much free copper can suddenly be released from the liver that it can kill them.70 Therefore this may be additional indication that people who have a serum infection should be guarded from fear. Free serum copper may be useful to someone with intestinal disease so that he can operate optimally. In addition, the vigor of copper’s absorption may even be increased in babies in a diarrhea situation because of the decline in cortisol mentioned previously. Thus diarrhea bacteria would have the use of less copper. I have no assurance that this is the case in adults, and indeed corticosterone works differently in adult rats.71 This may be part of the subtle difference in response suggested earlier in this paragraph, though. Also rats are a poor experimental animal for this concept because they do not secrete cortisol. They probably were able to lose that secretion because they have a marked inhibition of cholera toxin by something in their intestinal fluid72 and because their ascending colon absorbs water under c-AMP stimulation unlike their descending colon and other mammals.73 Rats should not be used for any experiments involving immunity, and perhaps better for none.

Copper in the Diet

A copper deficiency is possible even without the inappropriate requirements of a potassium deficiency proposed. Processing food often lowers copper content. The standard hospital diet is less than 2 mg per day.74 Diets of free choice are consistently less than 2 mg per day.75 The unpopularity of the rich source, liver, and the high cost of shellfish reinforce this situation for poor people not in the military (the military provides occasional shellfish). 2 mg per day is thought to be the minimum daily requirement76 and I suspect that 4 mg per day would be the safest intake.

Lending some support to this contention is the circumstance that underground Utah copper miners had 15.1 accidents per 200,000 man hours with no lost time vs 10.9 accidents with lost time to give a ratio of 1.4. The figures for all underground Utah noncopper miners were 4.4 and 8.4, giving a ratio of 0.5 77 as computed from bureau of mines statistics. This would seem to indicate that copper miners are tougher than other miners, since each injury is less likely to cause lost time for copper miners. Also, the greater number of injuries to copper miners suggests that their greater toughness tends to make them more careless. The figures might have been even further apart if injuries not connected to strength such as eye injuries and burns had been removed from the data. New Jersey copper smelter workers Have 8% of injuries as back injuries vs. 20% for all other occupations.78 Finnish copper miners are said to have much less arthritis and the women miners less anemia then other Finns.79 Finns have a lower copper intake than Americans, and as little as one half the intake of Africans and Asians,80 probably partly because of a high milk intake. Finns have the highest arthritis rate in the world,31 possibly partly because of perspiration losses during saunas. Such figures suggest an environmental cause rather than genetic, and probably not climatic because Laplanders not much further north have a lower rate, while Masai people join the Finns probably because of their milk intake also as well as low vegetation in the diet. Men who suffer from aneurysms always have much lower body and liver copper contents upon autopsy than others.8 Young women are not as affected by copper deficiency as men generally because estrogen enhances absorption.82 I suspect that this is an adaptation to furnish babies with sufficient copper to surmount the low intake while nursing milk. This is evidence that disruption of copper in arthritis is secondary because women have arthritis much more often than men. A pervasive copper deficiency would be suggested from the beneficial effects of copper supplements on such diverse diseases as anemia, rheumatoid arthritis, ulcers, infection, cancer, and seizures as discussed by Sorenson,83 since these diseases are common in our society. Copper supplement has healed slipped disks (in combination with pharmaceuticals).84 If these diseases are related to copper there should be a correlation between them, but I have no information for this. In addition, any problem which is a function of strength of elastin tissue has a high probability of being accentuated by a copper deficiency. Several of these symptoms together would make the probability of a copper deficiency existing very high indeed and anything which would reduce or interfere with copper very dangerous.

Copper Sources

If I am correct in this, there should be very little of these strength of elastin tissue diseases among people who eat a lot of shellfish, especially east coast oysters. Some of the advantage of east coast oysters may have disappeared now that the copper smelters have moved west to be near the mines. Shellfish use a copper pigment instead of iron to transport oxygen. Squid and sour bugs are included for this circumstance. Squid has a fairly large fraction of the copper in the skin.85 It may be that they use the skin for excretion because the skin also contains much of the cadmium. Copper tends to mute the toxic effects of cadmium and silver.86 Even so, it is probably best not to use the skin. The richest source of all is sheep liver, about two times cow liver and duck liver, and about ten times all other livers.87 These other livers range from about 7 to 14 mg per pound. Dog and cat foods are also high in copper because copper is added. I do not know what the averages are for them. However, they are probably a good source for poor people.

Non-leafy vegetables have about 1 mg per pound. Legumes have a range the same as most livers, as do some oil seeds. Cereal grains are about half this. However do not be misled by figures based on weight for food which contains no water. Foods containing water have to be multiplied by the inverse of the water content to be comparable. A dried apricot has exactly the same mineral content as it had directly from the field, for instance, per calorie. Leafy vegetables are probably higher than starchy vegetables, but I have no figures at present. Honey is very low, comparable to milk.88 Drinking water can contribute as much as 0.8 mg per day if it comes through copper pipes. Soft water and acid water contribute the largest amount.89 Copper bracelets are a rather ineffective source, but can have a small measurable effect on arthritis, especially in summer.90 It probably would be significant if a dozen or so wide bracelets were worn in summer, especially if they were corroded. I suppose for people who refuse to gain copper any other way it would be better than no way.

Milk

The poorest unprocessed source is milk. It contains less than ¼ mg per pound. This may be an adaptation to protect the mammary glands or the baby against microorganism growth. Babies solve their copper problem with large stores in their liver. Adults who eat large amounts of milk would be at grave risk if they had no other good source of copper. Milk is the food scientists use when they wish to create a copper deficiency in animals. This low copper content may be part of the large increase in cardiovascular disease which has been statistically associated with milk.91 Milk is a greater risk factor than smoking cigarettes. All the cheeses are included in this category. The necessity of dealing with this circumstance is no doubt the reason for the different handling of copper by women vs men and the strong effect of female hormones on copper physiology. The lesser effects of copper supplements on women with arthritis,92 the much less rate of aneurysms among women, and the tendency for these differences to recede as women get older is probably related to that necessity. What little copper is in milk must be part of its cellular components. Copper must be virtually unavailable to most bacteria attempting to live in milk, and this may be the reason why women evolved the ability to give their babies copper through liver storage rather than by milk content.

Interfering Food Elements

Eating large amounts of zinc interferes with absorption of copper.88 Eating large amounts of vitamin C (ascorbic acid) is thought to interfere with utilization of copper within the body.93 I do not know what the mechanisms are. Gaining carbohydrate in the form of sucrose or fructose will more than triple the mortality from ruptures in the top of the heart in copper deficient rats.94 Phytates which are found in wheat tend to decrease absorption.95 A copper metabolism poison has been found in one of the wild nightshade plants,96 so that it is conceivable that the tame nightshades, tomatoes, potatoes, egg plants, peppers, and tobacco have vestiges of something similar. Sulfide acts to inhibit absorption,97 which might be of interest to those who still take sulfur and molasses. The minimum daily requirement must then be partly a function of the status of one’s other nutrition. I feel that it should be possible to receive enough copper even if all the above interferences are present, although I know of no research which establishes this. Someone who is receiving marginal amounts of copper, however, appears to me to be in grave danger if even a few of the above interferences are present. It may be prudent to cut back on most of them.

Copper Toxicity

Too much copper is toxic. The amounts showing acute toxicity are large. A man sized pig must receive 200 mg to show obvious acute signs.98 About ten times this amount is a favorite way to commit suicide in Bombay, India.99 I suspect that a chronic toxicity for years can cause loss of weight, swollen liver, high blood pressure (salt intolerant), impotence, loss of ability to excrete potassium resulting in nighttime muscle spasms, and lymphedema. Some of these symptoms probably arise from a concurrent zinc deficiency because of interference with absorption. I suspect that swelling of prostrate tissue via a zinc deficiency accounts for some of the above symptoms. Some members of society are or may be at great risk from toxicity. People who have Wilson’s disease (a genetic inability to synthesize ceruloplasmin), one of the three most common forms of schizophrenia.100 and babies head the list. Diabetics are more efficient at absorbing copper,101 and may have a narrow safe range. Two mg per day has been recommended for copper deficient babies,102 but I suspect this is too high. Premature babies are usually born with too small a liver reserve to get safely past the nursing period, but one must use care with supplements. I suspect that a seat of the pants criteria for such babies would be no more totally than what their liver would have contained had they been born normally. A full term baby has 230 parts per million of copper in its liver,103 or 105 mg per pound of liver. I know of no way to determine clinically how much it actually contains although modern ultra sound devices should determine liver size. Some blood cell enzyme activities have been proposed as a good criteria.104 Serum contents are not a reliable indicator since infections, emotional stress, and possibly potassium deficiency have an overriding effect. Liver biopsies are impractical. Hair analysis is ambiguous and subject to contamination.

Copper combined with a wide range of chelating agents have been recommended for rheumatoid arthritis.105 I have no evidence that such a strategy is unusually dangerous. However, I think some caution is in order because when lysyl oxidase activity increases, blood pressure does also.106 I suspect that this is an adaptation to help protect arteries weakened by copper deprivation from rupturing. If massive doses are given it is conceivable that this protection could be defeated before arteries have a chance to strengthen. Elastin has a fairly high turnover107 and lysyl oxidase has a half life of only 16 hours. However strengthening is hardly instantaneous. I suspect one must allow at least a week for sure significant strengthening. Collagen is thought to have a very low108 rate of turnover, so repairs to blood vessels may be especially at risk. A normal body contains only 150 mg of copper,109 so even someone containing only half of normal should be able to correct a deficiency in a reasonable time with a total intake no more than ten mg per day (8 mg supplement), but cutting intake back to 4 or 5 mg total upon repletion.

It is possible that growth of funguses is enhanced by free copper. Growth is certainly enhanced by externally applied copper. That large amounts of copper can be toxic should definitely not make one reluctant to use reasonable copper supplements if you are not in one of the copper abnormal groups mentioned above. For normal people on a marginal diet I suspect that a supplement of 4 mg per day would be adequate and very desirable. People eating unprocessed food devoid of milk and in an active life probably usually need no supplements. However if you have a slow healing spinal disk, varicose veins, shaving cuts, hemorrhoids, or emphysema I would warmly recommend at the very least considering eating shellfish. Elastin diseases are extremely dangerous.

Effect on Society

The degenerative diseases mentioned above are among the most destructive, painful, and numerous in our society. If copper status is the most important parameter affecting them as I suspect, increasing copper intake should have a dramatic effect on our collective health. That copper is below optimum in a large number of people is virtually certain from current evidence. People vary considerably in their genetic makeup, and there are several dozen enzymes and hormones containing or affecting copper, so it should not be surprising that the symptoms of rheumatoid arthritis and the other diseases above should vary greatly or that “spontaneous” remissions are possible. When you further consider that other nutrients and circumstance also vary enormously, especially for those eating processed food, it is not safe to assume that copper is not deficient because all the symptoms are not present. Any symptom should trigger consideration of increased intake from some source. It seems to me that injections of GRMF and interleukin-1 along with other hormones secreted by T-cells would be of considerable value in fighting AIDS if done right. Small amounts injected every ten minutes or so would be the only efficacious way since the half life of the protein hormones is usually low, as little as 6 minutes in the case of cachectin.110 If Tcells prove to be responsible for mobilizing copper but the hormone can not be isolated, I would suspect that ceruloplasmin should be injected also. If secretion of immune hormones responsible for removing cancer in the body such as the synergism which has been demonstrated between interferon and cachectin for breast cancer111 prove to be dependent on copper for maximum production, ceruloplasmin injections may be in order for people who refuse to eat copper as well as injections of those hormones. If injections of these hormones are the only way to resolve the situation many small injections are the way it should be done. Massive injections once a day such as are currently used are both ineffective and dangerous. Frequent injections may seem irritating to the patient and unprofitable to the medical profession, but the main consideration is to get rid of the disease. When the hormone massively injected is insulin, wild swings in other hormones are also created, notably 18 hydroxy deoxycorticosterone (the potassium retaining hormone)112 and probably cortisol also. It is possible that diabetics subjected to such drastic swings have the disadvantages of some of the worst effects of both the high and low states, especially in the case of cortisol. It may be the source of the health problems that diabetics are afflicted with unless the loss of glucagon which is also secreted by the isles of Langerhan is causing the problem.

I would also suspect that if strains of bacterial diarrheas could be developed genetically devoid of their ability to synthesize the c-AMP stimulating enterotoxin and encapsulated in an enteric tablet in overwhelming numbers in order to avoid destruction by stomach acids, it might be possible to prevent most of the potassium loss implied in those diseases by competition of the mutant strain with wild cholera and thus not be hung on the cortisol system to survive. It might also prove to prevent the disease during an epidemic. When the patient goes back to eating food again, it might be a good idea to start with foods low in copper such as milk and honey, and of course oral rehydration salts including potassium.

There is no excuse for humans to have a copper deficiency. Shellfish are excellent sources and have already been part of successful farming procedures (oysters) or have a high probability of being able to be farmed (shrimp). In addition there are vast tonnages in antarctic krill. Furthermore some species of terrestrial snails are considered pests and actually exterminated. For those who have religious or quasi-religious convictions, or taste instincts against eating shellfish or liver, supplements are inexpensive. There is enough copper in one small electric motor to keep a whole town supplied for a long time. Better the copper into supplements than into a motorized wheel chair. Most of the references for this paper are available in Medical Hypotheses, 15;

p. 333, 1984.