Copper is a confusing mineral
Health properties of copper
How much copper do you need?
Factors causing copper deficiency
Tests for copper deficiency
Symptoms of copper deficiency
Cuprous versus cupric copper
Food sources of copper
Copper is a confusing mineral
Many health-aware people think that copper is something we get in excess. Doctors and popular health writers warn us about copper accumulation through copper plumbing and cookware. Some even refer to copper as a toxic mineral. However, the reality is that most people are copper-deficient. This is a critical deficiency because copper is one of the most important trace minerals in our diet. Copper is essential for many processes in the body, including the production of most proteins, enzymes and hormones.
Copper deficiency is a primary cause of many modern diseases such as coronary heart disease, stroke, atherosclerosis, inflammation, anaemia, old skin and rapid ageing, fatigue, grey hair, osteo arthritis, rheumatoid arthritis, cancers and many psychological, brain and nervous disorders.
Why is copper deficiency not widely acknowledged and copper not widely supplemented? The answer is that there are several confounding factors:
- There are no quick and reliable tests for copper deficiency. Worse, some tests are misleading. For example a hair test can show excess copper when the body is copper-deficient. Several blood enzyme tests show sufficiency when more of the enzyme is required for full function.
- The cuprous and cupric forms of copper are opposites. Cuprous (chemical) is toxic and can accumulate in the liver and other parts of the body. Cupric (biological) is essential and healthy, its levels are finely controlled and any excess is completely excreted within hours.
- There are many forms in which copper can be supplemented, each with its own disadvantages. Supplementing copper is not easy. Getting sufficient copper in the diet is also difficult.
- Copper compounds cannot be patented. Copper is one of those cheap, traditional remedies that prevents or heals numerous ailments, with no side-effects. (9, 94) For this reason, it has been ignored or even deliberately discredited by the pharmaceutical industry. There is about 80mg of copper in the body of a healthy man weighing 70 kg. In a pregnant woman, the amount of copper is higher. The liver is the organ that contains the most copper (8mg), with nearly as much in the brain. The kidneys have 1.2mg and the heart 0.9mg. (100) Most of the copper in our bodies is bound to transport proteins (ceruloplasmin and copper-albumin), storage proteins (metallothioneins), or copper-containing enzymes. (64)
Health properties of copper
- Formation of connective tissue. People with a sufficient copper have a younger skin. Their blood vessels, hearts, joints and membranes are strong and flexible. (25, 73, 74, 75, 76, 77, 78, 79, 80, 102, 105)
- Hair, skin and eye pigmentation. Copper is required for natural coloured hair, and it removes grey hair. (101)
- Bone formation. (10)
- Antioxidant. The ability of copper to easily accept and donate electrons explains its important role in oxidation-reduction (redox) reactions and in scavenging free radicals. Copper is an essential cofactor for oxidation-reduction reactions involving copper-containing oxidases. (25) The presence of sufficient copper prevents both cellular oxidation and oxidation of other proteins. (93) In one study, an intake of 7 mg per day for 6 weeks improved antioxidant defence. (44) Superoxide dismutase catalyses the conversion of free radicals (reactive oxygen species) to hydrogen peroxide, which is then reduced to water by other antioxidants. Ceruloplasmin functions as an antioxidant, binding both free copper and iron ions. (44, 106)
- Infections. Copper is an effective remedy for bacterial, protozoan and fungal infections. (This is in addition to its promotion of the immune system.) All copper salts are effective fungicides.
- Cancer. Copper sufficiency lowers the risk of cancers, and is necessary for recovery from cancers. (69) Copper is a remedy for aggressive metastatic cancer, reduces colon cancer, (3) and cures skin cancers. (84) Various copper complexes (such as copper salicylate) decrease tumour growth and increase survival rates. (4) Many copper complexes with superoxide dismutase activity retard the development of cancers. (5) Copper stimulates the production of the tumour-suppressor protein p53, which inhibits the growth of tumours in the body. (6, 7)
- Anti-inflammatory. Copper salicylate has a stronger anti-inflammatory effect than cortisone and none of the side-effects. The therapeutic index (the margin between effectiveness and toxic effects) of copper salicylate is significantly greater than for other anti-inflammatory drugs. (17, 26, 85)
- Repair. Copper promotes rapid healing of wounds, bones and intestines. (4, 8, 9, 10, 11, 12, 13, 14, 15, 90) Copper is necessary for healthy bones. (42)
- Energy production. Copper sufficiency is essential for mitochondrial energy production. It is required for physical and mental energy, and stamina. (68)
- Brain, nerves, neurotransmitters. Many reactions in the brain and nervous system are catalysed by cuproenzymes. A healthy brain, spinal cord and nervous system require sufficient copper.
- Hormone synthesis. Copper sufficiency is required for the production of numerous hormones, including endorphins, serotonin, dopamine, oxytocin, and other brain chemicals. Increased tissue copper has been found to increase brain enkephalins. (16) Copper complexes reduce pain and may activate opioid receptors. (17) A higher-copper diet increases the DHEA level in the body. (18)
- Pregnancy. Copper sufficiency is essential before and during pregnancy. Copper requirements increase during pregnancy. (100) Deficiency can cause brain abnormalities in the child in areas involved in learning, memory, coordination and movement. Foetal copper deficiency reduces free radical defence mechanisms, connective tissue metabolism, and energy production. (19, 20, 21, 22, 23, 24)
- Longevity. Copper is required for numerous anti-ageing processes including increasing the maximum number of cellular generations; repairing cellular DNA damage; and promoting production of various anti-senescence proteins. Animals with higher levels of antioxidant CuZnSOD have longer lifespans. An increased copper intake has been found to reduce protein glycation. (2, 73) Cellular DNA damage is decreased. (50)
How much copper do you need?
One estimate is that 80% of the population in the USA is copper-deficient. (3) The average American gets 0.9 mg of copper per day, a level that studies show causes severe cardiovascular problems in animals. (95)
The current RDI (Recommended Dietary Intake by the US Food and Drug Administration) for copper is 2 mg per day. (43) Most adults excrete about 1.3 mg of copper per day. If they sweat a lot, they can lose an additional 0.34 mg per day. (59) If you are getting less than 2 mg per day, it is easy to become copper-deficient. (60)
One study (61) concluded that to prevent copper deficiency 2.6 mg per day of copper is required. Most nutritionists recommend a daily copper dosage between 1 and 3 mg. (43) Several scientists who have studied copper and its health benefits take 4 mg daily. Other studies have found that 4-7 mg daily supplemental copper has resulted in benefits such as reducing cellular oxidation damage, lowering LDL cholesterol and raising HDL. (93) This level of copper intake may reduce the risk of many degenerative diseases. (95)
The World Health Organization gives 10 mg per day as the tolerable upper limit of copper intake. Most nutritionists recommend not exceeding 10 mg of copper daily. Remember that copper works synergistically with other minerals and nutrients. Copper needs to be taken in the correct ratio with zinc and other minerals like iron in order to maximise absorption. (107) Most scientists suggest that the ideal ratio of zinc to copper in the diet is 5:1. However I have seen recommendations from popular health writers from as low as 1:1 to as high as 9:1. Ageing and sickness is associated with extreme high or low ratios. (110)
If you are supplementing with large amounts of any copper antagonists, your copper needs will increase. For example, consuming large amounts of vitamin C (>800 mg) or zinc (>15 mg) per day will affect on your copper requirement.
Those with genetic disorders affecting copper metabolism (such as Wilson's disease, Indian childhood cirrhosis) should not supplement copper.
Factors causing copper deficiency
- Copper antagonists. Zinc is an antagonist to copper and inhibits its absorption. (81, 107) Other antagonists to copper include vitamin C, (71) iron, (106) manganese and molybdenum. (56, 82) Those who have been supplementing with copper antagonists such as zinc, iron, vitamin C, manganese, molybdenum and possibly selenium may be copper-deficient.
- "White monkey syndrome" is a good example of copper deficiency caused by excessive zinc. This syndrome develops in infant baboons kept in galvanized (zinc-coated) cages. By touching their cages all day, the baboons develop elevated zinc and low copper. In young baboons, this causes loss of pigment in skin and hair (hence the name "white monkey syndrome"), immune deficiency, alopecia, severe dermatitis and several other ailments. (56, 57, 81)
- Diet. The standard American diet (SAD) avoids traditional foods that are usually rich in copper, and is based on sweet and processed foods that are usually copper-deficient. A diet high in fructose, sucrose and other refined sugars will lower your copper level. (2, 58, 103, 104) Those on the SAD prefer muscle meat to other sources of protein. Muscle meat is rich in zinc and iron, but low in copper. Iron and zinc drive out copper from the body. In contrast, most organ meats such as liver and kidney are rich in copper. So those who consume muscle meat as opposed to organ meat and who do not consume enough seafood, tree nuts and legumes, are at severe risk of copper deficiency. A study showed that rats fed a muscle meat based diet had 23% lower bone density compared to the control animals. (42) Most processed foods and multi-vitamin/mineral supplements are high in iron and zinc, and low in copper.
- Pyroluria. Those who suffer from pyroluria are low in zinc, and have to supplement with zinc for the remainder of their lives. This heavy zinc supplementation causes a loss of copper. At first, those with pyroluria (who have not yet been supplementing with zinc) may have high copper levels. However, after they start supplementing zinc, they may go from abnormally high copper levels to abnormally low copper levels, because zinc and copper are antagonists to each other. Those with pyroluria who have been supplementing zinc for a long period are at risk of copper deficiency. Unfortunately, there is virtually no literature on pyroluria and its effects on copper requirements. Please contact me at Grow Youthful if you find research or have experience - Thanks, David Niven Miller.
- Malnutrition or prolonged diarrhoea.
- Celiac disease, cystic fibrosis, malabsorption syndromes.
- Prolonged use of cortisone or cortical steroids. Elevated cortisol. Unresolved stress.
- Pregnant or lactating mothers. The foetus or infant get priority access to the available copper.
- Children fed on cow's milk formula and not breastfed (cow's milk is relatively low in copper).
- Gastric bypass. (91)
- Premature infants.
Tests for copper deficiency
Unfortunately there is no easy and reliable test for copper sufficiency or deficiency. Blood, hair, urine and saliva tests for copper are usually unreliable. (51, 88) Hair tests are often misleading, as it is possible to have a high level of copper in the hair while being copper-deficient in the body. The lack of clear and reliable tests of human copper sufficiency make it difficult to determine how much supplemental copper you need for optimum health or to prevent chronic disease.
One of the most reliable tests is a liver biopsy. This is often used by farmers after the slaughter of their animals, but obviously is it not normally used on humans. It does mean that farm experience with feeding and copper supplementation is often valuable for humans.
Copper deficiency doesn't necessarily lower the level of copper-dependent enzymes, so tests for cuproenzyme levels may not be reliable. However, copper deficiency does significantly lower their activity. For example, lysyl oxidase is the main enzyme involved in the cross-linking of collagen and elastin, vital for the strength and flexibility of connective tissue in our skin, blood vessels, bones and other organs. In a copper-deficient person the level of lysyl oxidase looks normal. However, activity of this enzyme can be reduced by more than 50%. (92)
For the above reasons, the most practical quick test available is simply whether you are showing symptoms of copper deficiency. The hallmarks of copper deficiency are connective tissue disorders (prematurely aged, loose and weak skin), heart disease manifested by weak/distended/damaged blood vessels, and osteoporosis.
Symptoms of copper deficiency
Obvious and severe copper deficiency is not common. Marginal, chronic deficiency causing a variety of long-term chronic ailments is more the norm.
- Rapid ageing. Copper deficiency may be the main reason why our skin and hair lose their health and vitality as we age. Reduced production of various anti-senescence proteins. Hair goes grey or white. Grey hair loses its curls and becomes fine and straight.
- Loose or sagging skin, wrinkles, skin looks older than it should be. The only way to remove wrinkles and tighten skin is with the restoration of collagen synthesis.
- Slow wound healing.
- Antioxidant disruption, causing accelerated ageing and poor immune defence. Copper sufficiency increases the production of antioxidants. Copper protects tissues from reactive oxygen species, reactive carbonyl species, and other oxidants. Copper helps to block the activity of oxidising iron.
- Fatigue and low energy. Copper is required by the oxidative energy metabolism.
- Inflammation. Copper deficiency reduces the production of anti-inflammatory proteins such as ceruloplasmin in serum. Copper deficiency increases the severity of inflammation. (4, 8, 9, 26, 10) Note: an increase in serum copper is a physiological response to inflammation, rather than a cause of inflammation.
- Weak connective tissue. Evidenced by heart and blood vessel problems such as enlarged heart, weak aorta with holes and ruptures, aneurisms, varicose veins, hernia. (102, 105)
- Cardiovascular disease. (33, 95) Increased lipid peroxidation of lipoproteins and cardiovascular tissue. Studies show that copper deficiency increases plasma cholesterol, "bad" LDL cholesterol and blood pressure, (35, 36, 108, 109) while decreasing "good" HDL cholesterol. (37, 38, 39, 40, 41, 93)
- Atherosclerosis. Copper deficiency promotes atherosclerosis. (95) Severe copper deficiency results in heart abnormalities and damage (cardiomyopathy) in animals. (43, 95) A study found that copper supplementation of 3 to 6 mg daily increased the resistance of red blood cells to damaging oxidation, indicating that relatively high intakes of copper protect LDL and red blood cells from oxidation. (44, 93)
- Heart attack. Copper supplementation can minimise damage to the aorta and heart muscle following myocardial infarction. Rats on a copper-deficient diet had a decrease in aortic integrity that eventually produced aortic aneurysms. (6) A prospective cohort study in the US found that deaths from coronary heart disease was higher among those with the highest serum copper levels. (87) However, serum copper largely reflects serum ceruloplasmin and is not a good indicator of copper nutritional status. (88)
- Stroke, increased risk. (95)
- Anaemia. One of the most common signs of copper deficiency is anaemia that is unresponsive to iron supplementation but corrected by copper supplementation. Anaemia is a sign of both iron and copper deficiency. (27) Iron may accumulate in the livers of those who are copper-deficient. Copper-containing ceruloplasmin is required for iron transport to the bone marrow for red blood cell formation. Copper deficiency can lead to ceruloplasmin deficiency and hepatic iron overload and / or cirrhosis. (86)
- Arthritis. Patients with both rheumatoid arthritis (4) and osteoarthritis are often copper-deficient. (8) Dietary studies show they may consume too little zinc, magnesium and especially copper. (29)
- Bone ailments such as osteoporosis, formation of bone spurs, scoliosis, skeletal abnormalities and susceptibility to fractures. A study of elderly people found a decreased loss of bone-mineral density from the lumbar spine after copper supplementation of 3 mg daily for two years. In contrast, healthy adult males on a low-copper intake (0.7 mgs daily) for six weeks exhibited an increased rate of bone breakdown. (9, 30, 31, 32, 42)
- Bone, joint, muscle problems, painful joints and other chronic conditions involving bone and connective tissue.
- Weak muscle. Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength.
- Digestive problems. Copper is a treatment for numerous digestive problems (72) including stomach ulcers. (11) Unlike aspirin and other salicylates which break down stomach wall structure and cause bleeding, copper aspirinate provides the copper for stomach wall strength.
- Intolerance to milk - copper is required to produce lactase, the enzyme used to digest milk.
- Psychological / Neurological ailments.
- ADD / ADHD.
- Pain sensitivity increased.
- Impaired brain development. Young rats with copper-deficient brains exhibited altered behaviour and neurological characteristics. (36, 45, 83) The copper-based enzyme SOD enzyme protects the brain from oxygen free radicals, which brain cells produce in abundance. Low SOD due to insufficient copper causes oxidative brain damage. Copper is essential for a number of other brain enzymes, nerve mediators and hormones. (46)
- Depression. Copper deficiency causes reduction in the pleasure-producing brain enkephalins, and impaired brain function.
- Impaired nerve growth.
- Alzheimer's. There is increasing evidence that copper dietary deficiency may be a primary cause of Alzheimer's disease. (47) Copper-deficient brains are prone to beta-amyloid accumulation. (48, 49, 99)
- Weakened immune system. Increased risk of infections by viruses, bacteria, fungi and parasites. Animals deficient in copper have an increased susceptibility to bacterial pathogens such as salmonella and listeria. (50, 51, 52, 53, 54, 55) Low white blood cell (neutrophil) count. Immune impairment can start as quickly as a week after the removal of copper from the diet. Conversely, the addition of adequate copper to the diet can reverse the immune suppression within a week. (50) The immune system is so sensitive to copper deficiency that decreased immune cell function is an accurate indicator of marginal copper deficiency. (51) Studies show that copper deficiency leads to low interleukin 2, decreased proliferation of T-cells and reduced number of neutrophils and macrophages. (52) Even marginal copper deficiency reduces neutrophil's ability to destroy microorganisms such as Candida albicans.
A study of copper-deficient infants found that the ability of their white blood cells to destroy pathogens significantly increased after one month of copper supplementation. (53)
Another study found that men on a low-copper diet (0.66 mg of copper a day for 24 days, and then 0.38 mg a day for another 40 days) showed a decreased ability of their mononuclear cells to respond to antigens. (54)
A study showed that marginally copper-deficient rats had low white blood cell counts. In both rats and humans copper deficiency causes poor functionality of macrophages. (50, 55)
- Diabetes - increased risk.
- Obesity - increased risk.
- Thyroid - underactive. Hypothyroidism.
- Impaired growth and low weight in infants. (19)
Cuprous versus cupric copper
In this inorganic, unbound, non-biological form, cuprous copper is not efficiently excreted and can accumulate in the body. (72, 89, 97) This is the toxic form of copper which is not normally found in a healthy human body. Nearly all cuprous copper compounds are colourless when in solution in water. They are easily oxidised and less stable than most other copper compounds. Most of them will not dissolve in pure water, but will dissolve in acidic water.
Examples of cuprous copper compounds include:
- Cuprous oxide, a red or reddish-brown crystal or powder.
- Cuprous chloride, a white or grey coloured powder.
- Cuprous bromide, clear or colourless when pure.
- Cuprous iodide, a white powder.
- Cuprous sulphide, a black powder.
Most people get their municipal water through copper pipes. If the copper pipes are in constant use, the build-up of cuprous copper in the water flowing through them is insignificant. However, if the water is slightly acidic and the pipes are not used for many hours or days, then cuprous copper compounds can build up in the water. The presence of other chemicals in the water such as chlorine, for example, may compound the problem.
Another situation in which metallic copper and an acid environment access the human body is with a copper IUD contraceptive device. Copper cookware is yet another situation where acids in food or drink can come into contact with metallic copper. For most people, their tap water is not significantly acid (or alkaline). If you are concerned, the solution is to flush out the pipes before drinking such water. Run the cold tap long enough to flush water from your supply connection (usually by the water meter) to the tap.
Naturally high levels of copper in the sources of municipal water are not common. (89) Water with a copper level of more than 2 mg per litre is usually cloudy or has a blue or green tinge or blue/green particles. You can see the discolouration it if you put a litre of such water in a white bowl or container. If you boil it the water or particles may change colour to brown or black and the particles may float to the surface. If you have this much copper in your water supply, you need to carefully consider how much copper you are getting, and in what form (cuprous or cupric) as there is a risk of copper toxicity. (97)
In this organic, bound, biological form, cupric copper is more precisely controlled and quickly excreted from the body.
Cupric copper compounds dissolve in pure water, and are blue or blue-green colour in solution. They are more stable than other copper compounds. Cupric copper is the bio-available form of copper, which is essentially non-toxic as any excess is quickly excreted from the body. In its organic cupric form, the liver regulates copper with speed and precision. (61, 62) Bile is the major pathway for the excretion of copper.
In a study, scientists tried to create an elevated level of copper in blood plasma by injecting dogs and healthy human volunteers with high doses of cupric copper. All the excess copper in their blood disappeared within hours. In another study, 50 mg of cupric copper (25 times the RDI) was injected into healthy human volunteers. It completely disappeared from their blood in 4 hours. (64)
In another study, researchers gave healthy adults 4-8 mg of cupric copper a day for 1 to 3 months. This moderately high dosage did not change their copper plasma concentration because copper is so quickly and efficiently excreted. (65, 66)
Simple cupric compounds include:
- Cupric oxide, a black powder.
- Cupric chloride, a yellow/brown powder.
- Cupric sulphate, blue-coloured crystals or powder.
- Other examples include cupric sulphate-pentahydrate and cupric chloride-dihydrate.
- Amino acids form stable chelate complexes with cupric forms of copper.
It is virtually impossible to overdose on copper by eating high-copper foods. However, it is possible to get an excess of copper from cuprous forms of copper.
Copper toxicity is rare. Acute copper poisoning has occurred through the contamination of acidic drinks stored in copper-containing containers. Immediate symptoms of severe copper toxicity include abdominal pain, vomiting and diarrhoea (all of which purge the copper). Over time, copper toxicity can cause liver damage, kidney failure, psychosis, coma, and then death. (96)
In healthy adults, doses of up to 10mg of copper per day have not resulted in liver damage, so this level was set as the World Health Organization's upper limit. Those with genetic disorders affecting copper metabolism (such as Wilson's disease or Indian childhood cirrhosis) may be at risk of copper toxicity at significantly lower copper intake levels.
Copper inhibits or opposes zinc, iron, magnesium, manganese and molybdenum, and vitamin C, folic acid, vitamin B1 and vitamin E. Excess copper may cause low levels of all these minerals and vitamins, but particularly a low level of vitamin C (and all the consequences of insufficient vitamin C). (71, 82) On the other hand, it is possible that your copper levels could be abnormally high if you have abnormally low levels of copper antagonists in your body. Low zinc levels can occur with untreated pyroluria, for example.
Many of the symptoms of excess copper are similar to those of insufficient copper: immune problems, hormone upsets, painful joints, psychosis and upsets to brain function, liver damage. (73, 74, 75, 76, 77, 78, 79, 80, 83, 96)
Estrogen dominance (via xenoestrogens) is associated with copper excess. (69)
Food sources of copper
Broadacre and conventional farming strips the copper content from soil. In addition, the use of superphosphate and nitrogenous fertilisers prevent the uptake of copper. A study showed that the copper content in a variety of foods halved between 1942 and 1966. (95) Since then it has only got worse, so most foods that used to provide copper are now severely deficient. Australian soils were generally copper-deficient to start with, even before modern farming.
The richest food sources of copper are liver and other organ meats, oysters and other shellfish, cacao nibs, cocoa and black chocolate and red meat.
Other foods which may include copper depending on the soils and circumstances include apples, apricot kernels, avocado, bananas, barley, bee pollen, beetroot, blackstrap molasses, brewer's yeast, broccoli, buckwheat, burdock, butter, chicken, chickweed, coconut, dandelion greens, echinacea, eyebright, eggs, fennel, fish, garlic, golden seal, green beans, legumes especially lentils, mushrooms, oats, olives, oranges, parsley, peaches, pork, prunes, radish, raisins, red wine, seaweed, sesame seeds (unhulled), soy beans, split peas, sunflower seeds, tomato puree, tree nuts (mainly cashews, and then brazils), wheat bran, wheat germ.
A high quality traditionally-made red wine is usually rich in organic copper, and may be responsible for the "French paradox" (in addition to its beneficial resveratrol content).
In certain regions well water may be a source of copper, but you first need to ascertain what kind of copper. In Grow Youthful I maintain that the best water of all is the outflow from mountain glaciers or previous glacial regions. This water is rich in a wide variety of health-giving minerals, including copper.
Vegetarians may absorb copper less efficiently than non-vegetarians. A study found that lacto-ovo vegetarians averaged 1.45 mg of copper per day of which 0.48 mg was absorbed. In contrast, the non-vegetarians averaged 0.94 mg of copper per day of which 0.39 mg was absorbed. (67)
The best way to get copper is by eating copper-rich foods. If you are pregnant or ill, do not supplement except under your doctor's supervision. Take care to use high quality supplements, and measure quantities carefully.
Symptoms of copper deficiency may be rapidly reversed by copper supplementation. (68) The dose required depends on the problems being treated and the condition of the patient.
Warning: do not apply copper compounds to open cuts, inflamed or very sensitive skin as it may cause irritation and pain. Alternatively, use it very diluted.
Dry skin does not absorb copper very well. Most copper salts do not easily pass through dry skin, but absorption is increased if the skin is damp. Different people may get different results, in particular depending on their skin's acidity. When copper is in contact with the skin, and the skin is not acidic, it forms chelates with components of human sweat and this aids its skin absorption.
Copper is a remedy and a preventative, especially when an ingredient in other medicines. (28)
The most common forms in which copper may be supplemented
Copper gluconate is the most common form in which copper is supplemented. It is less tightly bound than salicylate, so should be used with care and only taken with food. Other amino acid chelates are also used, but gluconate is generally preferred.
Copper salicylate is the most stable form in which to supplement copper, both orally and transdermally. It does not alter liver or blood chemistry as much as other copper compounds do, because it is so stable. (84) Copper salicylate may be directly applied to the skin at the site of the problem - a painful joint, arthritis, skin cancer, ulcer, aged skin or grey hair. To penetrate the skin, it needs to be kept moist for many minutes or longer. After applying the copper salicylate, magnesium oil, aloe vera, MSM or DMSO can also be applied, and then covered with a damp cloth to keep it moist. DMSO is the most effective carrier through the skin.
Copper aspirinate (copper acetyl-salicylic acid, the copper complex of aspirin). This is more effective than normal aspirin, and does not have the harmful side-effects of aspirin, probably because normal aspirin binds to copper in the gut, whereas copper aspirinate provides copper, so there is no deficiency on the gut wall.
Copper ascorbate, which has strong anti-viral properties.
Copper sulphate. Like copper gluconate, it is well utilised but can oxidise if not coated.
Other forms in which copper may be taken include cupric oxide, copper citrate, copper acetate and other copper amino acid chelates. None are as effective as gluconate and salicylate forms.
Copper in drinking water (with the exception of natural mountain mineral water or glacial water) is NOT a good way to supplement copper. One study of rabbits showed that trace amounts of copper in their drinking water harmed their brains. (98) This was confirmed in another study. (99)
Copper bracelets. Another way to supplement copper is with a copper bangle or bracelet, though the amount of copper that you get from a bracelet is relatively low. After years of experience, many people have discovered that copper armbands reduce arthritis and improve both physical and mental health. Copper metal on the skin has a long history of traditional use, with numerous anecdotal reports of effectiveness in the treatment of arthritis and a variety of other ailments, and as a "youthing" supplement.
Most symptoms of copper deficiency can be explained by the ineffective activity of one or more copper-dependent enzymes. For instance, lack of pigmentation can be explained by a tyrosinase deficiency, and the defects of collagen and elastin causing abnormalities in the connective tissue and vascular system can be explained by a lysyl oxidase deficiency.
Copper is required to produce more than a dozen important enzymes (cuproenzymes), including: Cytochrome-c oxydase is required for oxidative mitochondrial energy production within cells. It plays a critical role in cellular energy production by the mitochondria creating the ATP energy-storing molecule. (68) This enzyme also breaks down vitamin C. Myelin requires cytochrome c oxidase for its synthesis.
Lysyl oxidase is needed to produce and cross link collagen and elastin for healthy connective tissue in skin, joints and blood vessels. The copper-containing protein copper-zinc superoxide dismutase (CuZnSOD) provides the primary antioxidant defence in the human body. It is a potent antioxidant for protection against free radicals.
Tyrosinase is required to produce the pigment melanin, essential for skin and hair pigmentation. (101)
Ceruloplasmin-ferrosidase, an antioxidant needed by the iron metabolism and for iron transport.
Dopamine hydroxylase and dopamine-beta-monooxygenase, required for the production of hormones such as dopamine, noradrenaline and adrenalin (epinephrine). Dopamine betahydroxylase catalyses the conversion of dopamine into norepinephrine.
Other copper-based enzymes include amine oxidase, lysine-6 oxidase and peptidylglycine monooxygenase. (1)
Your comments about any of your experiences - positive or negative - with your use of copper are welcome at Grow Youthful. I am always curious about your use of and experience with natural remedies, and your feedback is very welcome.
1. Camakaris, J, I Voskoboinik, JF Mercer.
Molecular mechanisms of copper homeostasis.
Biochem Biophys Res Commun 261, no. 2 (1999): 225-32.
2. Saari JT, AM Bode, GM Dahlen. Defects of copper deficiency in rats are modified by dietary treatments that affect glycation. J Nutr 125, no. 12 (1995): 2925-34.
3. Davis CD, WT Johnson. Dietary copper affects azoxymethane-induced intestinal tumor formation and protein kinase C isozyme protein and mRNA expression in colon of rats. J Nutr 132, no. 5 (2002): 1018-25.
4. Sorenson JR, W Hangarter. Treatment of rheumatoid and degenerative diseases with copper complexes: A review with emphasis on copper-salicylate. Inflammation 2, no. 3 (1977): 217-38.
5. Oberley, LW, SW Leuthauser, RF Pasternack, TD Oberley, L Schutt, JR Sorenson. Anticancer activity of metal compounds with superoxide dismutase activity. Agents Actions 15, no. 5-6 (1984):535-8.
6. Greene, FL, LS Lamb, M Barwick, NJ Pappas. Effect of dietary copper on colonic tumor production and aortic integrity in the rat. J Surg Res 42, no. 5 (1987): 503-12.
7. Narayanan, VS, CA Fitch, CW Levenson. Tumor suppressor protein p53 mRNA and subcellular localization are altered by changes in cellular copper in human Hep G2 cells. J Nutr 131, no. 5 (2001): 1427-32.
8. Sorenson JR. Evaluation of copper complexes as potential anti-arthritic drugs. J Pharm Pharmacol 29, no. 7 (1977): 450-2.
9. Dollwet HH, JR Sorenson. Historic uses of copper compounds in medicine. Trace Elements in Medicine 2, no. 2 (1985): 80-87.
10. Sorenson John R. Roles of copper in bone maintenance and healing. Biol Trace Elem Res 18 (1988): 39-48.
11. Sorenson JR, K Ramakrishna, TM Rolniak. Antiulcer activities of D-penicillamine copper complexes. Agents Actions 12, no. 3 (1982): 408-11.
12. Alzuet, G, S Ferrer, J Borras, JR Sorenson. Anticonvulsant properties of copper acetazolamide complexes. J Inorg Biochem 55, no. 2 (1994): 147-51.
13. Morgant, G, NH Dung, JC Daran, B Viossat, X Labouze, M Roch-Arveiller, FT Greenaway, W Cordes, JR Sorenson. Low-temperature crystal structures of tetrakis-mu-3,5-diisopropylsalicylatobis-dimethylformamidodico pper(II) and tetrakis-mu-3,5- diisopropylsalicylatobis-diethyletheratodicopp er(II) and their role in modulating polymorphonuclear leukocyte activity in overcoming seizures. J Inorg Biochem 81, no. 1-2 (2000): 11-22.
14. Lemoine, P, B Viossat, G Morgant, FT Greenaway, A Tomas, NH Dung, JR Sorenson. Synthesis, crystal structure, EPR properties, and anti-convulsant activities of binuclear and mononuclear 1,10-phenanthroline and salicylate ternary copper(II) complexes. J Inorg Biochem 89, no. 1-2 (2002): 18-28.
15. Viossat, B, FT Greenaway, G Morgant, JC Daran, NH Dung, JR Sorenson. Low-temperature (180K) crystal structures of tetrakis-mu-(niflumato)di(aqua)dicopper(II) N,N-dimethylformamide and N,Ndimethylacetamide solvates, their EPR properties, and anticonvulsant activities of these and other ternary binuclear copper(II)niflumate complexes. J Inorg Biochem 99, no. 2 (2005): 355-67.
16. Bhathena, SJ, L Recant, NR Voyles, KI Timmers, S Reiser, JC Jr Smith, AS Powell. Decreased plasma enkephalins in copper deficiency in man. Am J Clin Nutr 43, no. 1 (1986): 42-6.
17. Okuyama, S, S Hashimoto, H Aihara, WM Willingham, JR Sorenson. Copper complexes of nonsteroidal antiinflammatory agents: Analgesic activity and possible opioid receptor activation. Agents Actions 21, no. 1-2 (1987): 130-44.
18. Klevay, LM, DM Christopherson. Copper deficiency halves serum dehydroepiandrosterone in rats. J Trace Elem Med Biol 14, no. 3 (2000): 143-5.
19. Ebbs, JH, FF Tisdall, WA Scott. The influence of prenatal diet on the mother and child. J Nutr 22, no. 5 (1941): 515-26.
20. Morton, MS, PC Elwood, M Abernethy. Trace elements in water and congenital malformations of the central nervous system in south wales. Br J Prev Soc Med 30, no. 1 (1976): 36-9.
21. Keen, CL, JY Uriu-Hare, SN Hawk, MA Jankowski, GP Daston, CL Kwik-Uribe, RB Rucker. Effect of copper deficiency on prenatal development and pregnancy outcome. Am J Clin Nutr 67, no. 5 Suppl (1998): 1003S-11S.
22. Lonnerdal B. Copper nutrition during infancy and childhood. Am J Clin Nutr 67, no. 5 Suppl (1998): 1046S-53S.
23. Hawk, SN, L Lanoue, CL Keen, CL Kwik-Uribe, RB Rucker, JY Uriu-Adams. Copper-deficient rat embryos are characterized by low superoxide dismutase activity and elevated superoxide anions. Biol Reprod 68, no. 3 (2003): 896-903.
24. Penland, JG, JR Prohaska. Abnormal motor function persists following recovery from perinatal copper deficiency in rats. J Nutr 134, no. 8 (2004): 1984-8.
25. Itoh, S, K Ozumi, HW Kim, O Nakagawa, RD McKinney, RJ Folz, IN Zelko, M Ushio-Fukai, T Fukai. Novel mechanism for regulation of extracellular SOD transcription and activity by copper: Role of antioxidant-1. Free Radic Biol Med 46, no. 1 (2009): 95-104.
26. Giampaolo, V, F Luigina, A Conforti, R Milanino. Copper and inflammation. In Inflammatory diseases and copper: The metabolic and therapeutic roles of copper and other essential metalloelements in humans. Edited by JR Sorenson. Clifton, New Jersey: Humana Press, 1982.
27. Hart, EB, H Steenbock, J Waddell, CA Elvehjem. Iron in nutrition. VII. Copper as a supplement to iron for hemoglobin building in the rat. 1928. J Biol Chem 277, no. 34 (2002): e22.
28. Sorenson John R. Inflammatory diseases and copper: The metabolic and therapeutic roles of copper and other essential metalloelements in humans. Experimental biology and medicine. Clifton, New Jersey: Humana Press, 1982.
29. Kremer JM, J Bigaouette. Nutrient intake of patients with rheumatoid arthritis is deficient in pyridoxine, zinc, copper, and magnesium. J Rheumatol 23, no. 6 (1996): 990-4.
30. Conlan D, R Korula, D Tallentire. Serum copper levels in elderly patients with femoral-neck fractures. Age Ageing 19, no. 3 (1990): 212-4.
31. Jonas J, J Burns, EW Abel, MJ Cresswell, JJ Strain, CR Paterson. Impaired mechanical strength of bone in experimental copper deficiency. Ann Nutr Metab 37, no. 5 (1993): 245-52.
32. Baker, A, L Harvey, G Majask-Newman, S Fairweather-Tait, A Flynn, K Cashman. Effect of dietary copper intakes on biochemical markers of bone metabolism in healthy adult males. Eur J Clin Nutr 53, no. 5 (1999): 408-12.
33. Elsherif, L, RV Ortines, JT Saari, YJ Kang. Congestive heart failure in copper-deficient mice. Exp Biol Med (Maywood) 228, no. 7 (2003): 811-7.
34. Cartwright GE, MM Wintrobe. The question of copper deficiency in man. Am J Clin Nutr 15 (1964): 94-110.
35. Klevay LM. Hypertension in rats due to copper deficiency. Nutr Rep Int 35 (1987): 999-1005.
36. Klevay LM, ES Halas. The effects of dietary copper deficiency and psychological stress on blood pressure in rats. Physiol Behav 49, no. 2 (1991): 309-14.
37. Klevay LM, DM Medeiros. Deliberations and evaluations of the approaches, endpoints and paradigms for dietary recommendations about copper. J Nutr 126, no. 9 Suppl (1996): 2419S-26S.
38. Klevay LM. Trace elements, atherosclerosis, and abdominal aneurysms. Ann N Y Acad Sci 800 (1996): 239-42.
39. Klevay LM. Cardiovascular disease from copper deficiency - a history. J Nutr 130, no. 2S Suppl (2000): 489S-92S.
40. Klevay LM. Dietary copper and risk of coronary heart disease. Am J Clin Nutr 71, no. 5 (2000): 1213-4.
41. Klevay LM. Ischemic heart disease as deficiency disease. Cell Mol Biol (Noisy-le-grand) 50, no. 8 (2004): 877-84.
42. Klevay LM, RE Wildman. Meat diets and fragile bones: Inferences about osteoporosis. J Trace Elem Med Biol 16, no. 3 (2002): 149-54.
43. Trumbo, P, AA Yates, S Schlicker, M Poos. Dietary reference intakes for vitamin A, vitamin K, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. J Am Diet Assoc 101, no. 3 (2001): 294-301.
44. Rock E, A Mazur, JM O'Connor, MP Bonham, Y Rayssiguier, JJ Strain. The effect of copper supplementation on red blood cell oxidizability and plasma antioxidants in middle-aged healthy volunteers. Free Radic Biol Med 28, no. 3 (2000): 324-9.
45. Prohaska JR, RG Hoffman. Auditory startle response is diminished in rats after recovery from perinatal copper deficiency. J Nutr 126, no. 3 (1996): 618-27.
46. Lutsenko S, A Bhattacharjee, AL Hubbard. Copper handling machinery of the brain. Metallomics 2, no. 9 (2010): 596-608.
47. Klevay LM. Alzheimer's disease as copper deficiency. Med Hypotheses 70, no. 4 (2008): 802-7.
48. Hung, YH, EL Robb, I Volitakis, M Ho, G Evin, QX Li, JG Culvenor, CL Masters, RA Cherny, AI Bush. Paradoxical condensation of copper with elevated beta-amyloid in lipid rafts under cellular copper deficiency conditions: Implications for Alzheimer disease. J Biol Chem 284, no. 33 (2009): 21899-907.
49. Cater, MA, KT McInnes, QX Li, I Volitakis, S La Fontaine, JF Mercer, AI Bush. Intracellular copper deficiency increases amyloid-beta secretion by diverse mechanisms. Biochem J 412, no. 1 (2008): 141-52.
50. Bala S, ML Failla. Copper deficiency reversibly impairs DNA synthesis in activated T lymphocytes by limiting interleukin 2 activity. Proc Natl Acad Sci U S A 89, no. 15 (1992): 6794-7.
51. Bonham M, JM O'Connor, BM Hannigan, JJ Strain. The immune system as a physiological indicator of marginal copper status? Br J Nutr 87, no. 5 (2002): 393-403.
52. Percival SS. Copper and immunity. Am J Clin Nutr 67, no. (5 Suppl) (1998): 1064S-68S.
53. Heresi, G, C Castillo-Duran, C Munoz, M Arevalo, L Schlesinger. Phagocytosis and immunoglobulin levels in hypocupremic infants. Nutrition Research 5, no. 12 (1985): 1327-34.
54. Kelley DS, PA Daudu, PC Taylor, BE Mackey, JR Turnlund. Effects of low-copper diets on human immune response. Am J Clin Nutr 62, no. 2 (1995): 412-6.
55. Babu U, ML Failla. Copper status and function of neutrophils are reversibly depressed in marginally and severely copper-deficient rats. J Nutr 120, no. 12 (1990): 1700-9.
56. Klevay LM. Iron overload can induce mild copper deficiency. J Trace Elem Med Biol 14, no. 4 (2001): 237-40.
57. Frost PA, GB Hubbard, MJ Dammann, CL Snider, CM Moore, VL Hodara, LD Giavedoni, R Rohwer, MC Mahaney, TM Butler, LB Cummins, TJ McDonald, PW Nathanielsz, NE Schlabritz-Loutsevitch. White monkey syndrome in infant baboons (papio species). J Med Primatol 33, no. 4 (2004): 197-213.
58. Klevay LM. Metabolic interactions among dietary choletstrol, copper, and fructose. Am J Physiol Endocrinol Metab 298, no. 1 (2010): E138-9.
59. Jacob, RA, HH Sandstead, JM Munoz, LM Klevay, DB Milne. Whole body surface loss of trace metals in normal males. Am J Clin Nutr 34, no. 7 (1981): 1379-83.
60. Williams DM. Copper deficiency in humans. Semin Hematol 20, no. 2 (1983): 118-28.
61. Chambers A, D Krewski, N Birkett, L Plunkett, R Hertzberg, R Danzeisen, PJ Aggett, TB Starr, S Baker, M Dourson, P Jones, CL Keen, B Meek, R Schoeny, W Slob. An exposure-response curve for copper excess and deficiency. J Toxicol Environ Health B Crit Rev 13, no. 7-8 (2010): 546-78.
62. Cabrera A, E Alonzo, E Sauble, YL Chu, D Nguyen, MC Linder, DS Sato, AZ Mason. Copper binding components of blood plasma and organs, and their responses to influx of large doses of (65)Cu, in the mouse. Biometals 21, no. 5 (2008): 525-43.
63. Boal, AK, AC Rosenzweig. Structural biology of copper trafficking. Chem Rev 109, no. 10 (2009):4760-79.
64. Gubler CJ, ME Lahey, GE Cartwright, MM Wintrobe. Studies on copper metabolism. IX. The transportation of copper in blood. J Clin Invest 32, no. 5 (1953): 405-14.
65. Harvey, LJ, G Majsak-Newman, JR Dainty, DJ Lewis, NJ Langford, HM Crews, SJ Fairweather-Tait. Adaptive responses in men fed low and high-copper diets. Br J Nutr 90, no. 1 (2003): 161-8.
66. Turnlund, JR, WR Keyes, SK Kim, JM Domek. Long-term high copper intake: Effects on copper absorption, retention, and homeostasis in men. Am J Clin Nutr 81, no. 4 (2005): 822-8.
67. Hunt JR, RA Vanderpool. Apparent copper absorption from a vegetarian diet. Am J Clin Nutr 74, no. 6 (2001): 803-7.
68. Uauy, R, M Olivares, M Gonzalez. Essentiality of copper in humans. Am J Clin Nutr 67, no. 5 Suppl (1998): 952S-59S.
69. John R. Lee. What Your Doctor May Not Tell You About Breast Cancer. 2002.
70. Aminoff MJ. Pharmacologic management of Parkinsonism and other movement disorders. In: Katzun BG (editor), Basic & Clinical Pharmacology. Prentice Hall International, London. 1995:419-431.
71. Finley EB et al. Influence of ascorbic acid supplementation on copper status on young adult men. American Journal of Clinical Nutrition, 47:96-101, 1988.
72. Knobeloch L, et al. Gastrointestinal upsets and new copper plumbing - is there a connection? WMJ 1998 Jan 97;1, 9-53.
73. Kivirikko K, et al. Abnormalities in copper metabolism and disturbances in the synthesis of collagen and elastin. Med Biol. 60:45-48, 1982.
74. Adam, M, H Pohunkova, O Cech, J Vachal. A. [The effect of collagenous gel on endoprosthesis anchoring]. Acta Chir Orthop Traumatol Cech 62, no. 6 (1995): 336-42.
75. Adam, M, O Cech, H Pohunkova, J Stehlik, Z Klezl. B. The role of collagen implants containing the tripeptide gly-his-lys in bone healing process. Acta Chir Orthop Traumatol Cech 62, no. 2 (1995): 76-85.
76. Ahmed, MR, SH Basha, D Gopinath, R Muthusamy, R Jayakumar. Initial upregulation of growth factors and inflammatory mediators during nerve regeneration in the presence of cell adhesive peptide-incorporated collagen tubes. J Peripher Nerv Syst 10, no. 1 (2005): 17-30.
77. Ehrlich, HP. Stimulation of skin healing in immunosuppressed rats. Presented at the Symposium on collagen and skin repair Reims, France, Sept 12-13 1991.
78. Huang, PJ, YC Huang, MF Su, TY Yang, JR Huang, CP Jiang. In vitro observations on the influence of copper peptide aids for the led photoirradiation of fibroblast collagen synthesis. Photomed Laser Surg 25, no. 3 (2007): 183-90.
79. Maquart, FX, P Gillery, JC Monboisse, L Pickart, M Laurent, JP Borel. Glycyl-l-histidyl-l-lysine, a triplet from the a2 (I) chain of human type I collagen, stimulates collagen synthesis by fibroblast cultures. Ann N Y Acad Sci 580 (1990): 573-75.
80. Maquart, FX, L Pickart, M Laurent, P Gillery, JC Monboisse, JP Borel. Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-l-histidyl-l-lysine-Cu2+. FEBS Lett 238, no. 2 (1988): 343-6.
81. Van Campen DR. Zinc interference with copper absorption in rats. Journal of Nutrition, 91:473, 1967.
82. Van den Berg, GJ et al. Dietary ascorbic acid lowers the concentration of soluble copper in the small intestinal lumen of rats. Br J Nutr. 71(5):701-707, 1994.
83. Walsh W. Zinc deficiency, metal metabolism and behavioural disorders. A report of the health research institute. March 1996.
84. Bland J. Copper Salicylates and Complexes in Molecular Medicine. Int Clin Nutr Review 4, 3, 130-134, 1984.
85. Sorenson John R. Copper Chelates as possible Active Metabolites in the Antiarthritic and Antiepileptic Drugs. J Applied Nutrition 32, 1&2, 4-25, 1980.
86. Thackeray EW, Sanderson SO, Fox JC, Kumar N. Hepatic iron overload or cirrhosis may occur in acquired copper deficiency and is likely mediated by hypoceruloplasminemia. J Clin Gastroenterol. 2011;45(2):153-158.
87. Ford ES, et al. Serum copper concentration and coronary heart disease among US adults. Am J Epidemiol. 2000;151(12):1182-1188.
88. Bertinato J, Zouzoulas A. Considerations in the development of biomarkers of copper status. J AOAC Int. 2009;92(5):1541-1550.
89. Araya, M, MC McGoldrick, LM Klevay, JJ Strain, P Robson, F Nielsen, M Olivares, F Pizarro, LA Johnson, KA Poirier. Determination of an acute no-observed-adverse-effect level (noael) for copper in water. Regul Toxicol Pharmacol 34, no. 2 (2001): 137-45.
90. Downey, D, WF Larrabee, V Voci, L Pickart. Acceleration of wound healing using glycyl-histidyllysine copper (II). Surg Forum 25 (1985): 573-75.
91. Ernst, B, M Thurnheer, B Schultes. Copper deficiency after gastric bypass surgery. Obesity (Silver Spring) 17, no. 11 (2009): 1980-1.
92. Gacheru, SN, PC Trackman, MA Shah, CY O'Gara, P Spacciapoli, FT Greenaway, HM Kagan. Structural and catalytic properties of copper in lysyl oxidase J Biol Chem 265, no. 31 (1990): 19022-7.
93. Klevay LM. Extra dietary copper inhibits LDL oxidation. Am J Clin Nutr 76, no. 3 (2002): 687-8; author reply 88.
94. Sorenson JR, LS Soderberg, MV Chidambaram, DT de la Rosa, H Salari, K Bond, G.L Kearns, RA Gray, CE Epperson, ML Baker. Bioavailable copper complexes offer a physiologic approach to treatment of chronic diseases. Adv Exp Med Biol 258 (1989): 229-34.
95. Raymond A. Schep. Cardiovascular Disease in the Western World - an Overlooked Risk Factor. Rose Croix Journal, 2014, Vol 10, 72-88.
96. Bremner I. Manifestations of copper excess. Am J Clin Nutr. 1998;67(5 Suppl):1069S-1073S.
97. Fitzgerald DJ. Safety guidelines for copper in water. Am J Clin Nutr. 1998;67(5 Suppl):1098S1102S.
98. Sparks DL, Schreurs BG. Trace amounts of copper in water induce beta-amyloid plaques and learning deficits in a rabbit model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2003;100(19):11065-11069.
99. Kitazawa M, Cheng D, Laferla FM. Chronic copper exposure exacerbates both amyloid and tau pathology and selectively dysregulates cdk5 in a mouse model of AD. J Neurochem. 2009;108(6):1550-1560.
100. G. E. Cartwright, M. M. Wintrobe. Copper Metabolism in Normal Subjects. Am J Clin Nutr April 1964 vol. 14 no. 4 224-232.
101. Fatemi Naieni F et al. Serum iron, zinc, and copper concentration in premature graying of hair. Biological Trace Element Research 2012 Apr;146(1):30-4.
102. Pang Y et al. A longitudinal investigation of aggregate oral intake of copper. Journal of Nutrition 2001 Aug;131(8):2171-6.
103. Reiser S, J.C. Smith Jr., W. Mertz, J.T. Holbrook, D.J. Scholfield, A.S. Powell, W.K. Canfield, J.J. Canary. Indices of copper status in humans consuming a typical American diet containing either fructose or starch. The American Journal of Clinical Nutrition 1985 Aug;42(2):242-51.
104. Reiser S et al. Role of dietary fructose in the enhancement of mortality and biochemical changes associated with copper deficiency in rats. The American Journal of Clinical Nutrition 1983 Aug;38(2):214-22.
105. Dembinski K et al. Three distinct cases of copper deficiency in hospitalized pediatric patients. Clinical Pediatrics 2012 Aug;51(8):759-62.
106. Bastian TW et al. Maternal iron supplementation attenuates the impact of perinatal copper deficiency but does not eliminate hypotriiodothyroninemia nor impaired sensorimotor development. The Journal of Nutritional Biochemistry 2011 Nov;22(11):1084-90.
107. Sandstead HH. Requirements and toxicity of essential trace elements, illustrated by zinc and copper. The American Journal of Clinical Nutrition 1995 Mar;61(3 suppl):621S-624S.
108. O.M. Alarcon , Y. Guerrero, M. Ramirez de Fernandez , I. D'Jesus M. Burguera, J.L. Burguera, M.L. Di Bernardo. Effect of copper supplementation on blood pressure values in patients with stable moderate hypertension. Archives Latinoamericans de Nutrition 53(30)(2003): 271-276.
109. Henry C. Lukasaki, Lelsie M. Klevay, D.B. Milne. Effects of dietary copper on human autonomic cardiovascular function. European Journal of Applied Physiology 58 (1988): 74-80.
110. Andrea Mezzetti, Sante D Pierdomenico, Fabrizio Costantini, Ferdinando Romano, Domenico De Cesare, Franco Cuccurullo, Tiziana Imbastaro, Giuseppe Riario-Sforza, Franco Di Giacomo, Giovanni Zuliani, Renato Fellin. Copper/zinc ratio and systemic oxidant load: effect of aging and aging-related degenerative diseases. Free Radical Biology and Medicine, Volume 25, Issue 6, October 1998, 676-681.