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Copper Deficiency May Underlie Osteoporosis, Anemia and Neurodegenerative Disorders

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Copper plays a key role in many physiological processes, including myelination, neutrophil activation, hemoglobin formation, and antioxidant synthesis. Deficiency is very common but often unrecognized. Left uncorrected it can lead to serious conditions including anemia, collagen loss, poor immune function and neurodegenerative symptoms suggestive of multiple sclerosis. Photo: Nytumbleweeds; Agency: Dreamstime.com.

Despite their obviously different appearances, osteoporosis, anemia, neurodegenerative disorders, cardiovascular disease, and impaired cellular immunity may all be manifestations of chronic copper deficiency, an often-overlooked nutritional problem that is more common than many doctors realize.

Copper plays a key role in myelination of neurons, neutrophil activation, collagen synthesis, hemoglobin formation, and endogenous antioxidant synthesis. "It is a mineral that is greatly under-recognized and under-utilized," said Ron Grabowski, RD, DC, Professor of Clinical Practice at Texas Chiropractic College, Houston, and Director of Research for the American Chiropractic Association's Council on Nutrition.

Deficiency can manifest in many different ways including seizures and neurological problems, poor temperature control, connective tissue degeneration, bone mineral loss, pallor, anemia, and poor hair and skin quality. Several recent studies suggest that in addition to the well-recognized neural and hematologic sequelae, copper deficiency also has a role in diabetes and cardiovascular disease.

Copper excess can be problematic too, causing liver damage, neruologic problems, chondroplasia and skeletal abnormalities. But given the way most Americans eat, and the wide use of medications that interfere with copper uptake, deficiency is vastly more common than excess.

Dr. Grabowski contends that many patients diagnosed with iron-deficiency anemia, early-stage multiple sclerosis, and various immunodeficiency disorders actually have unrecognized copper deficiency. Fortunately, this is correctable via supplementation. It may take time, and it requires careful monitoring, but restoring healthy copper levels can greatly improve patients' health status.

Modest Requirements, Often Unmet

"Our daily need for copper is actually quite modest. For most adults, 1.5–3.0 mg/d is sufficient for good health. That doesn't sound like much, but more than 30% of people on a typical American diet are not even getting 1 mg per day. Another third of the population is not even reaching the minimum daily allowance (900 mcg)," said Dr. Grabowski.

The primary dietary sources of copper are shellfish (oysters, mussels, clams, lobster, crab, squid) and organ meats (beef liver, kidneys and heart). With a few exceptions like bananas, grapes, tomatoes, avocados and sweet potatoes, most produce lacks copper. Fortunately for vegetarians, nuts (cashews, filberts, macadamias, pecans, almonds, pistachios) and some legumes (peanuts, navy beans, lentils, soy) are good copper sources.

The rising prevalence of copper deficiency is due in part to the fact that many people are simply not eating as many copper-rich foods as they once did. The high prevalence of digestive disorders, and widespread use of drugs and supplements that deplete or interfere with copper are the other major factors.

Easily Absorbed, Easily Blocked

Copper absorption occurs in the upper portion of the small intestine. In people with a healthy digestive tract, it is absorbed very efficiently compared to other minerals. Any disease that affects digestion may interfere with copper absorption or promote copper loss in the lower GI tract. Think about deficiency in anyone with Crohn's disease, irritable bowel or any other inflammatory GI problem.

Proper copper absorption requires ample stomach acid. Consequently, drugs that block acid secretion impede copper uptake. This includes all proton pump inhibitors and H2 blockers. "In my practice. I see so much copper deficiency and also B12 deficiency in people on these medications," Dr. Grabowski told Holistic Primary Care.

High fructose consumption increases copper excretion in urine, and also increases demand for superoxide dismutase (SOD), an endogenous antioxidant the formation of which requires copper. "This is a big problem because high-fructose corn syrup is ubiquitous in the American food stream."

Be aware that whole grains contain phytates that bind copper, zinc and other minerals. This is not to suggest that people shouldn't eat whole grains, but they shouldn't take minerals at the same time. "People often do not understand that it matters when and with what they take their supplements. Don't take them with whole grain breads or brown rice; you won't get the benefits of the minerals. We need to harmonize supplements with our diets."

Copper & Zinc: A Dynamic Balance



Much like calcium and magnesium, copper and zinc have a sometimes synergistic, sometimes antagonistic relationship. Both are involved in a host of enzymatic and metabolic reactions. When the balance of zinc and copper is right, these processes proceed well. But, like calcium and magnesium, too much of one diminishes the other. Excesses of either zinc or copper can cause problems.

The first report of a pathologic zinc-induced copper deficiency came out 20 years ago. Mayo Clinic physicians described an individual who took high daily doses of zinc for 10 months. The patient presented with hypochromic-microcytic anemia, leukopenia and neutropenia. When iron failed to resolve the abnormalities, the physicians dug deeper and found extreme copper deficiency, correctable only with intravenous infusion of 10 mg cupric chloride for 5 days (Hoffman HH, 2nd, et al. Gastroenterology. 1988; 94(2): 508–512).

Zinc excess with copper deficiency is common, said Dr. Grabowski. "A zinc to copper ratio of 30:1 will really force people into serious copper deficiency. Some researchers say the problem begins at 10:1. When patients show me their multivitamins and I see 30 mg of zinc to 1 mg of copper, it makes me very, very nervous. The supplements they're taking to improve their health may actually be inducing a copper deficiency that increases their risk of disease."

Self-Induced Deficiencies

During the winter cold and flu season, many people unwittingly induce copper deficiency by gobbling zinc lozenges and heavy doses of vitamin C, believing this will enhance immunity and increase antioxidant capacity. But both zinc and vitamin C compete with or interfere with copper absorption. Because copper is essential for production and activation of neutrophils—the first line of defense against pathogens—excess zinc and vitamin C may actually render people more susceptible to the very ailments they're seeking to avoid.

Two recent papers review the role of copper and other trace minerals in both cellular and humoral immunity. Maggini and colleagues illustrate the vicious cycle occurring when micronutrient deficiencies suppress T-cell mediated and adaptive antibody responses, thus increasing susceptibility to infection, which, in turn, increases micronutrient loss, interferes with metabolism of many nutrients, and reduces nutrient intake (Maggini S, et al. Br J Nutr. 2007; 98(Suppl 1): S29–S35).

In the same journal, Munoz and colleagues point out that careful micronutrient supplementation can boost immune function and reduce infection susceptibility. This is particularly important in the elderly, because vaccinations against respiratory infections are only partially effective (Munoz C, et al. Br J Nutr. 2007; 98(Suppl 1): S24–S28).

Copper is essential for synthesis of one form of superoxide dismutase (SOD), and anything that reduces copper also reduces SOD, diminishing overall antioxidant capacity. People who take high dose vitamin C to boost their antioxidants may be surprised to learn they're actually inducing the opposite effect. Anything over 1,000 mg of vitamin C per day interferes with copper.

The best way to increase overall antioxidant capacity is by increasing intake of antioxidant rich foods, rather than amplifying one antioxidant vitamin out of the many, said Dr. Grabowski.

Iron, Copper & Anemia

Many doctors reflexively prescribe iron to any patient with signs and symptoms of anemia without actually testing to see if iron is deficient. According to Dr. Grabowski, many cases of alleged iron-deficiency anemia are actually due to copper deficiency. Like iron, copper is involved in hemoglobin formation. Suspect low copper if a patient's anemia does not resolve with additional iron.

"Copper deficiency can present exactly like iron deficiency and you'll never know the difference unless you test for it," he said. There is one other give-away, though: low neutrophil count. Copper is essential for neutrophil production and phagocytic activation. Copper-deficient people show low neutrophil counts, a feature not seen in iron deficiency anemia.

Of course, someone may be deficient in both iron and copper. "Copper has a part to play in iron uptake in the GI tract. If copper is low, iron absorption tends to be low as well."

In a just-published paper, Cleveland Clinic hematologists show hypocupremia as a cause in 3 cases of cytopenia and bone marrow failure, and suggest it should be added to the differential diagnosis of bone marrow failure syndromes, including myelodysplasia (Haddad AS, et al. Haematologica. 2008; 93(1): 1–5).

This corroborates a 5-case series from Washington University a few months earlier that also points to copper deficiency as a cause of myelodysplasia. In all 5 cases, the problem resolved with copper supplementation (Fong T, et al. Haematologica. 2007; 92(10): 1429–1430).

Copper & CVD

Several recent papers point to lack of copper as a risk factor for cardiovascular disease, but the picture is complex. University of Turin researchers looked at the relationship of dietary copper to a host of metabolic variables in 1,197 individuals. They found clear inverse relationships between copper and diastolic blood pressure, total cholesterol, LDL, blood glucose, uric acid, and total antioxidant status, a clearly high-risk profile. There were linear correlations between copper and both C-reactive protein and nitrotyrosine, a marker of oxidative stress (Bo S, et al. J Nutr. 2008; 138(2): 305–310).

The authors note that, "Marginal copper deficiency is associated with an unfavorable metabolic pattern, but copper supplementation might not be recommended in view of its association with inflammation and markers of oxidative stress."

In a new review article, Dr. Hamid Aliabadi of the Duke University Department of Neurosurgery notes that, "Dietary copper deficiency has been shown to cause a variety of metabolic changes, including hypercholesterolemia, hypertriglyceridemia, hypertension, and glucose intolerance" (Alibadi H. Med Hypotheses. 2008; epub ahead of print).

At the other end of the spectrum, excess copper and iron may contribute to acute myocardial infarction. Researchers at the University of Sindh, Pakistan studied serum and hair levels of zinc, copper and iron in samples from 130 MI patients and 61 healthy age-matched controls. They found consistently low zinc but high iron and copper in the MI patients, particularly those with second and third MIs, and those who died from MI versus those who survived (Kazi TG, et al. Clin Chim Acta. 2008; 389(1–2): 114–119).

Of Copper & Collagen

When people think about osteoporosis, they immediately think of calcium and vitamin D. Both are important for healthy bone. But copper is just as important, said Dr. Grabowski. It is essential for formation of the collagen component in bone, which is necessary for maintaining bone mineral density (BMD).

"I've had people come to me and say that they just had a BMD test done and they were surprised it was low, because they're taking vitamin D and calcium/magnesium. I'll do the tests, and yes, vitamin D, calcium and magnesium are fine. But then we look at copper, and it is very low. By supplementing with copper we may be able to improve BMD by improving bone collagen formation."

As a chiropractor, Dr. Grabowski sees many patients with musculoskeletal injuries. "They're taking all sorts of things: ibuprofen, Aleve (naproxen), high-dose vitamin C. None of these things will help create new collagen. But copper will."

Some people take high-dose vitamin C following physical injuries, believing it speeds tissue healing. But because copper is a key factor in collagen and elastin formation, and vitamin C interferes with copper, the excess vitamin may impede rather than facilitate wound healing.

Copper Deficiency & Demyelination: An MS Mimic?

In addition to collagen formation, copper plays a central role in myelin formation. Prolonged deficiency can result in demyelination and neurodegeneration, which shows up as spastic gait, optic nerve inflammation, peripheral neuropathy, and fatigue. In many ways, it is a near-perfect mimic of multiple sclerosis.

According to Dr. Neeraj Kumar, of the Department of Neurology at the Mayo Clinic, Rochester, MN, unrecognized copper deficiency is a common cause of idiopathic myelopathy in adults. "The clinical picture bears striking similarities to the syndrome of subacute combined degeneration associated with vitamin B12 deficiency," wrote Dr. Kumar, summing up a study of 13 Mayo Clinic patients (Kumar N, et al. Neurology. 2004; 13; 63(1): 33–39).

All had polyneuropathies, with pronounced gait difficulty and sensory ataxia. In addition to measurable copper deficiencies, 7 had high or high-normal zinc. Copper supplements restored circulating levels to normal or near normal in 7 of 12 evaluable patients; parenteral supplementation restored another 3. In all cases, repletion prevented further neurodegeneration; improvement of neurological function was variable.

Copper supplementation fairly easily reverses anemia and neutropenia, but neurologic deficits may be less responsive. "Improvement, when it occurs, is often subjective and preferentially involves sensory symptoms," he noted (Kumar N. Mayo Clin Proc. 2006 Oct; 81(10): 1371–1384).

An earlier paper by University of Oklahoma neurologists details two cases of myelopathy, neutropenia and anemia linked to copper deficiency and zinc excess (Prodan CI, et al. Neurology. 2002; 12; 59(9): 1453–1456). In both cases, "Hematologic recovery followed copper supplementation, both initially and after relapse off copper therapy, while serum zinc levels remained high and the neurologic abnormalities only stabilized."

Dr. Grabowski believes many patients diagnosed with MS actually have copper deficiencies. The idea is not so far-fetched. Neurologists have long recognized the value of vitamin B12 for MS, because the vitamin plays a key role in myelination. Most routinely check B12 in patients suspected of having MS. They tend to overlook copper, though it is just as important in myelination.

"It's not that copper deficiency causes MS. It's that copper deficiency causes demyelination, which can mimic or be mis-diagnosed as MS," Dr. Grabowski explained. "We don't really know if copper deficiency is involved in MS, or if giving copper to MS patients will help. But it is certainly worth thinking about."

Testing for and Treating Copper Deficiency



Copper supplementation requires careful monitoring. Patients should not try it by themselves, as it is easy to over-do it on copper, thus interfering with zinc.

Dr. Grabowski has found that serum testing for copper is not very reliable. Methods and norms often vary from lab to lab, as was pointed out in a recent study from the University of Ipswitch, UK (Twomey PJ, et al. Int J Clin Pract. 2007; epub ahead of print). Further, serum measurements don't show the extent to which copper is actually doing its job at the cellular level.

He told Holistic Primary Care that he much prefers the intracellular copper analysis recently introduced by SpectraCell Laboratories (www.Spectracell.com). This test shows copper levels in lymphocytes, and gives a much more accurate picture of how the mineral is taken up and utilized by cells.

Like all of SpectraCell's tests, the copper assay is based on the fact lymphocytes are the longest-lived cells in circulation, with a typical lifetime of 120 days or more. By way of comparison, neutrophils typically live for several hours to 13 days; platelets have a lifespan of 3–7 days; red blood cells live for 90–100 days. The nutrient content of lymphocytes provides a sort of time-elapsed composite picture of a patient's nutritional status over the last several months.

SpectraCell incorporates the copper test into its comprehensive Functional Intracellular Assessment (FIA) panel, which gives a broad survey of micronutrients and trace minerals. The FIA enables doctors to detect both deficiencies and excesses of various nutrients, and to track them over time. One can use it to assess the impact of supplementation not only on the target nutrient but on all other nutrients with which it interacts. In the case of minerals, the FIA panel details copper levels as well as iron, zinc, and other trace minerals. So one can see whether increasing copper is changing these others.

"When dealing with copper deficiencies, you need to look very closely at zinc. If I give copper supplements to try and correct a deficiency, I can end up throwing the zinc level way off. I have to test them both periodically," said Dr. Grabowski. "It's a balancing act, and one can go back and forth for long periods of time, increasing copper but lowering zinc, then increasing zinc but lowering copper, before one gets it right."

 

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