Hypercupremia - High Copper

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<h1>Hypercupremia - High Copper</h1>

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<div>By Natural Insight</div>

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<p>Hypercupremia is a state of high copper within the body that alters our biochemistry in such a prominent way, increasing the likelihood of neurological/behavioural alterations and mental illness. It can be caused by congenital (copper transfer from mother to baby via placenta), genetic and environmental factors. Genetic alterations result in improper functioning of the metallothionein protein (copper binding protein), with an inabilty of the body to control copper metabolism. The genetically determined condition, Pyroluria, also results in high copper levels, as large quantities of zinc are depleted from the body. Furthermore, xeno-oestrogens, hormone therapy (oestrogen dominance), water supply, cigarette smoking, long term stress (adrenal insufficiency) and nutritional imbalance (Zinc deficiency) all contribute to high copper in the body.

When copper enters the liver, hepatic pathways transform copper into ceruloplasmin (a serum protein). Usually most of the copper in our circulation is bound in the form of ceruloplasmin. In cases of adrenal insufficiency and exhaustion (long term stress), production of ceruloplasmin by the liver is significantly decreased, with a subsequent increase in free and unbound copper levels. High copper levels will actually effect the ability of both copper binding proteins, ceruloplasmin and metallothionein, to completely bind copper, creating a circular issue. Excessive copper results in widespread copper deposits in the body's tissues, and subsequent oxidative and neurological damage. When there is a combined genetic defect caused by pyroluria and/or improper functioning of metallothionein, there will be an increased sensitivity to heavy metals and vaccines, poor immune function, yeast overgrowth, high susceptibility to parasitic infections/viruses, leaky gut syndrome, gluten/casein/salicylate intolerance with an increased risk of developing Autism Spectrum Disorder's in children.

<strong>Hypercupremia - Common Observations</strong>

When high levels of copper are free and unbound in the bloodstream, they can create feelings of extreme fatigue, headache, nausea, irritability, moodiness and depression.High copper personality traits have been observed as soft, gentle, naive, intuitive people with caring, sensitive personalities. They are often youthful in looks and highly artistic. When copper levels are out of control they become excessively emotional, depressed, fearful, angry, violent, spacy with racing thoughts and appear to be living in a dream state. High copper people are often the ones observed as "living on the edge."As copper greatly impacts our biochemistry, it's not difficult to understand why high levels have been associated with the following conditions: allergies, anxiety, fatigue, paranoia, abnormal loss of hair, stuttering, tremour, opaquely white nails, hallucinations, anaemia, arthritis, acne, psoriasis, hypothyroidism, frontal headaches, premenstrual tension, sciatica, post partum psychosis, candida overgrowth, parasitic infections, eclampsia, fibromyalgia, prostatitis, infertility, hypertension, autism, ADHD, tinnitus, hypertension, anorexia, schizophrenia, parkinson's disease, bipolar disorder, depression, insomnia, neuralgia, senility, and functional hypoglycemia.

<strong>Copper and the Nervous System</strong>

Copper is a neurotoxin, and when present in high amounts it alters the levels of neurotransmitters in the body - low dopamine, high noradrenaline and variable changes in histamine levels.What's interesting is how heavily involved copper and histamine are in neurological processes. Histamine acts as a neurotransmitter in the body. It's mostly known for it's role in allergic response, but it also causes tears to flow, regulates sleep, determines pain sensitivity, and sexual libido. Dr. Carl Pfeiffer first discovered copper as a significant causative factor in histapenia (low histamine), a schizophrenic-like disorder, characterized by high serum copper and low serum histamine levels. Although many patients were previously classified as suffering from unresponsive schizophrenia, it was revealed they were suffering from Hypercupremia. Pfeiffer's hypothesis was that histamine is heavily degraded due to abnormally high levels of copper. In his clinical research histamine deficit and copper intoxication have been found to represent 50% of patients labelled as Schizophrenic. Chitre and Puniker also demonstrated significantly higher serum copper levels in diagnosed schizophrenics, with even higher levels seen in parkinson's disease; a condition characterised by low dopamine levels.

Copper functions to maintain the conversion of dopamine into noradrenaline, producing a long lasting "adrenaline rush." It can be challenging to settle down, sleep and turn off one's mind. The physiological result of high noradrenaline and adrenaline levels are mood swings, depression, mental agitation, over-stimulation, restlessness, anxiety, insomnia and racing thoughts.

The first discovery into the stimulant effects of copper were described by Ussing in 1949. He measured an increased electrical potential of a frog skin placed in a copper containing Ringer's solution. Using quantitative EGG, Pfeiffer and Goldstein demonstrated that only five milligrams of copper administered to male volunteers had the same stimulating effects on the central nervous system as 5 milligrams of d-amphetamine; a potent psychostimulant drug.

High copper levels also interfere with the body's most abundant inhibitory neurotransmitter Gamma Amino Butyric Acid (GABA). GABA provides a sense of calm and relaxation in the body and functions together with Glutamate, the body's main excitatory neurotransmitter, to provide a balance between excitation and inhibition of nerve cells. Excessive copper levels disrupt the Vitamin B6 dependant enzyme glutamate decarboxylase, inhibiting the conversion of Glutamate into GABA. This Glutamate/GABA imbalance results in high glutamate levels, resulting in impaired speech, aggressive behaviour, intense irritablity, anxiety, inflammation of the gastrointestinal tract (GIT), and eventually neuronal destruction.

Long term stress is a significant contributing factor in Hypercupremia. During emotional, mental or physical stress, the sympathetic nervous system initiates the "fight or flight" response. Subsequently adrenaline, cortisol and aldosterone are produced from the adrenal glands. This protective mechanism is useful in periods of crisis, where a burst of energy is needed; when a threat is perceived. The release of aldosterone increases retention of copper and sodium to provide this energy. Simultaneously zinc and magnesium (our calming nutrients) are excreted by the kidneys. The problem arises when this biochemical pattern occurs long term, as in cases of post traumatic stress disorder (PTSD), heavy drug use or chronic illness. The body retains excess copper causing further toxicity and degradation of the nervous system. Adrenal weakness, insufficiency and exhaustion are the result of long term stress and PTSD and can be further investigated through salivary cortisol and DHEA-S testing.

<strong>Copper and the Endocrine System</strong>

As seen in many clinical studies, ceruloplasmin and estrogen fluctuate together throughout a women's menstrual cycle and rise during pregnancy. In particular, estrogenic steroids have shown increased copper levels in rodents, chickens and women taking the oral contraceptive pill (OCP). Female patients in remission with schizophrenia, show a complete return of symptoms once resuming the OCP.

The mechanism by which estrogen increases copper levels is through overstimulation of aldosterone receptors in the kidneys, leading to sodium, copper and fluid retention. Both estrogen and copper contribute to raising blood pressure, by retaining fluid and increasing blood volume. An excess of copper is associated with PMS, infertility, miscarriages, post natal depression, polycystic ovarian syndrome, ovarian cysts and sexual dysfunction.

Copper can also accumulate in the thyroid gland, disrupting the conversion of thyroxine (T4) into triiodothyronine (T3). T3 is the active form of thyroid hormone. In situations of long term stress and zinc deficiency T4 is converted into higher levels of the inactive form of T3, known as reverse T3 (rT3). These two hormones, rT3 and T3, compete for uptake creating a vicious cycle that results in higher than normal rT3 and low T3 levels. The result is low T3 syndrome or Hashimoto's (Hypothyroidism).

Estrogen also directly contributes to thyroid disruption, particularly in cases of estrogen dominance. It chemically exhibits a similar structure to T3, able to block thyroid receptors sites on the cell membrane, inducing a form of hypothyroidism. Symptoms associated with hypothyroidism are fatigue, depression, brain fog, constipation, muscle cramps, excessive menstrual flow, intolerance to cold especially extremities, dry skin, dry, thinning hair, weight gain.

Since copper is so closely involved in estrogen, histamine and neurotransmitter metabolism, it's not difficult to see how an imbalance of this mineral has the potential to create havoc.

<strong>Zinc and Copper</strong>

Zinc and copper have a antagonistic relationship and both competitively inhibit one another for absorption. In a healthy body the ideal ratio of serum Copper:Zinc is between 0.7:1 and 1:1. In a recent pilot study undertaken by Stuckey, Walsh, and Lambert, into the effectiveness of targeted nutritional therapy in the treatment of mental illness, serum Copper/Zinc ratio was seen as high as 2:1 in patients clinically diagnosed with mental illness. A balance of the ratio is more important than the amounts of either of these nutrients.

Zinc is crucial for the body when high copper levels are detected. It assists in insulin production, the formation of progesterone, testosterone, cortisol, aldosterone, neurotransmitters, antibodies, hydrochloric acid and digestive enzymes. It helps to protect the GIT lining, preventing intestinal permeability (leaky gut syndrome).

The best way to reduce copper in the body is with Zinc. It functions to promote excretion of copper through bile and inhibits intestinal absorption. Bremner reported up to 40% reduction in liver copper in zinc supplemented sheep. Manganese and Molybdenum have a synergistic action with Zinc in the removal of copper. Vitamin C is another effective copper antagonist demonstrated in clinical studies by Finley and Cerklewski.

A recent study performed by The Children's Institute in Pittsburgh, examined plasma zinc/serum copper ratio as a biomarker for children with autism spectrum disorders (ASD's). 230 children with autistic disorder, pervasive development disorder-NOS and Asperger's syndrome were tested. The entire group of children with ASD's displayed a mean zinc level of 77.2mcg/dl, mean copper level of 131.5mcg/dl, with a Zinc/Copper ratio of 0.608, well below 0.7 which is the cut off for the lowest 2.5% of healthy children. It was concluded that plasma zinc/serum copper may be an important biomarker of heavy metal toxicity in ASD's.

Zinc is also essential for those with the genetic condition known as Pyroluria; characterised by high copper levels, low serotonin, pyridoxal 5 phosphate (activated Vitamin B6), arachidonic acid and zinc. It is caused by a genetic abnormality in haemoglobin synthesis resulting in higher than normal levels of the byproduct hydroxyhemoppyrrolin-2-one (HPL). HPL binds available Zinc and B6, resulting in widespread biochemical imbalances and neurological symptoms.

<strong>Cadmium and Copper</strong>

An interesting speculation by Dr. Paul C Eck, is that high levels of cadmium, found in cigarettes and marijuana, can drive copper back into the body's stores. This might make a person feel better temporarily by reducing unbound copper in the blood.

<strong>Sources of Copper</strong></p>

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<li>Congenital - Copper is passed from mother to baby through the placenta. The developing baby and supportive pregnancy tissues act as chelators for copper, moving high copper from mother to baby. For this reason it's important to regulate copper levels before pregnancy.</li>

<li>Drinking water from copper piping, particularly the combination of easily dissolving copper in soft, acidic water can lead to extremely high concentrations of copper in water. Blue/green stains can often be seen in basins, showers, toilets where there is an excess. Copper sulfate is also added to drinking water in some areas to control algae growth.</li>

<li>Cigarette smoking.</li>

<li>Food sources particularly high in copper are nuts, chocolate, carob, grains particularly wheat, soybeans, coffee, avocado, liver, mushrooms, oysters, wheatgerm.</li>

<li>Food dyes rich in hydrazine (deplete zinc)</li>

<li>Multivitamin formulas often include copper in their formula.</li>

<li>Oral Contraceptive Pill.</li>

<li>Copper Intra-uterine devices.</li>

<li>Xeno-estrogens mimic estrogen due to a similar chemical structure and have the potential to influence copper retention. Examples of xeno-estrogens are: pesticides, plastics (particularly soft plastics like plastic bags and food wrap), volatile organic compounds (VOC's), growth hormones used on animals, and all petrochemical waste products used in the manufacturing of plastic, gasoline and other petrochemical derivatives.</li>

<li>As zinc is copper's natural antagonist, a diet low in zinc, digestive malabsorption of zinc or genetic biochemical influences (Pyroluria) can all contribute to altering the zinc copper ratio, leading to rising copper in the body.</li>

<li>Our soils are becoming widely deficient in trace minerals like zinc, manganese and selenium. These nutrients have the ability to control copper levels in our body.</li>

<li>Long term adrenal stress via increased aldosterone and consequent copper retention. Adrenal insufficiency resulting in lowered ceruloplasmin (copper binding protein).</li>

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<p><strong>Diagnostic Assessment</strong></p>

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<li>Blood - examines levels of ceruloplasmin and serum copper. A diagnosis of Hypercupremia is reached when serum levels rise to over 140mcg/dl, with accompanying low ceruloplasmin. It's important to look at plasma zinc to determine the ratio of copper:zinc.</li>

<li>Urine - patient is given penicillamine, and urine is collected over a 24 hour period.</li>

<li>Hair analysis - non-invasive, easily perfomed and an accurate measure of copper levels in the tissues. Ensure hair samples are from non dyed hair and taken from multiple places on the head.</li>

<li>Liver biopsy - used rarely in cases of Wilson's disease - a genetic disease where copper accumulates in the body.</li>

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<p><strong>Therapeutic Considerations</strong></p>

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<li>Adrenal and nervous system support - Zinc, magnesium, vitamin B complex, avoidance of stimulants (drugs, caffeine, sugar, food additives, glutamate), increase relaxation "switching off" time with meditation, yoga, breathing techniques, relaxation CD's, sauna therapy, exercise, rest, uninterrupted sleep.</li>

<li>Include copper antagonists - zinc, manganese, molybdenum, vitamin C. In particular zinc, folinic acid, pyridoxal 5 phosphate and selenium are also important for the production of metallothionine (copper binding protein). It's important to note that each individual will require differing doses of chelating minerals, depending on laboratory results and any other complications - methylation, pyroluria. Increasing Zinc levels needs to occur slowly to minimise aggravation of an already sensitive system. As zinc levels increase, copper slowly comes down as it's removed from the body. The removal process itself can often cause a temporary flare up of symptoms, which will slowly ease with time. Exacerbation of symptoms varies depending on level of copper in the tissues, number of gut pathogens (yeasts, parasites, bacteria) and overall vitality of the body. Symptoms of copper removal are commonly nausea, loose, frequent stools, headaches, over stimulation, insomnia, brain fog.</li>

<li>Avoid copper sources and in particular avoid copper in your drinking water through an appropriate filtration system.</li>

<li>Chelating agents - Zeolite is a crystalline structure formed from volcanic ash. It attracts and irreversibly binds and removes toxic heavy metals, including copper. Gentle on the liver and kidneys. To be used with extreme caution and under guidance of a qualified practitioner. Depending on one's current health status, chelation therapy may create more harm than good and must be supervised and done slowly when copper levels are very high or there are methylation issues or pyroluria present.</li>

<li>Improve detoxification - sulfur amino acids including cysteine and taurine will increase copper elimination. Note to be careful with these nutrients if you have a methylation issue with Cystathionine Beta Synthase (CBS) enzyme, as these nutrients will cause more probelms.</li>

<li>Increase intake of filtered copper free water.</li>

<li>Dietary considerations - eat lots of fresh, organic seasonal vegetables, opt for small amounts of whole grains (quinoa, buckwheat, brown rice) or better yet try grain free (GAPS or paleo style diet), and small portions of organic (hormone free) meat into your diet. Adjust diet to increase high zinc, low copper foods - red meat, eggs, pumpkins seeds, chicken. Reduce high copper foods - nuts, chocolate, wheat, soybeans, coffee, avocado, liver, mushrooms, oysters, wheatgerm. Ensure protein is eaten with each meal. Use sea salt rather than table salt, particularly in those with adrenal insufficiency, which may first be noticed by excessive sweet and salt cravings.</li>

<li>Digestive Support - Encourage gastrointestinal (GIT) mucosal healing and reestablish healthy levels of intestinal microbiota through probiotics, cultured food, anti-candida diet guidelines. The use of GIT healing supplements like Glutamine, Slippery Elm and DGL may be necessary in cases where food intolerance coexists or heavy damage has occurred from fungi or parasites. Copper imbalance creates an anaerobic environment in the GIT, a perfect breeding ground for yeast, fungi, parasite, bacteria. Anti-fungal/parasitic support may include Saccharomyces boulardii, Caprylic acid,<em>Artemisia absinthium</em>,<em>Tabebuia avellanedae</em>, and Citrus seed extract to clear pathogens from the body and eliminate their toxic metabolites. Long term Zinc deficiency, which occurs as a result of high copper levels, contributes to increased permeability of the gut lining, decreased hydrochloric acid levels and decreased immune function. All of these situations increase the likelihood of leaky gut syndrome, yeast overgrowth, and food intolerance.</li>

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<p>Hypercupremia appears a vital component in the analysis and understanding of the biochemical imbalances involved in behavioural disorders and mental illness. For this reason, investigation would appear essential for any patient exhibiting symptoms of anxiety, depression, chronic debilitating fatigue, stimulation behaviours, panic attacks, suicidal tendencies, paranoia or hallucinations.

A complete program designed by a qualified practitioner for balancing body chemistry, with an integrated nutritional, dietary and lifestyle program is essential. Using copper antagonists and chelates alone may not be enough to reestablish balance. Typical treatment can take a few months and up to 1-2 years in more complex cases where it may be neccesary to use specific nutritional supplements to bypass blockages within the methylation cycle.

<strong>© </strong>Copyright Insight Naturopathy 2012</p>

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<h2>References</h2>

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<li>Wilson, L., 2010, <em>Copper Toxicity Syndrome</em>, The Center for Development, viewed 1st February, 2011.<a href="http://www.drlwilson.com/articles/copper_toxicity_syndrome.htm">http://www.drlwilson.com/articles/copper_toxicity_syndrome.htm</a></li>

<li>Graham, B., <em>Major Mental Illness Biochemical Subtypes</em>, Nutritional Healing, viewed 1st February, 2011.<a href="http://www.nutritional-healing.com.au/content/articles-content.php?heading=Major%20Mental%20Illness%20Biochemical%20Subtypes">http://www.nutritional-healing.com.au/content/articles-content.php?heading=Major%20Mental%20Illness%20Biochemical%20Subtypes</a></li>

<li>Pfeiffer, C, C., Mailloux, R., 1987, <em>Excess Copper as a factor of human diseases</em>, Journal of Orthomolecular Medicine, Vol. 2, No. 3, viewed on 1st February, 2011.<a href="http://www.orthomolecular.org/library/jom/1987/pdf/1987-v02n03-p171.pdf">http://www.orthomolecular.org/library/jom/1987/pdf/1987-v02n03-p171.pdf</a></li>

<li>Taylor, C. J., Moore, G., Davidson, D. C., 1984, <em>The effect of treatment on zinc, copper and calcium status in children with phenylketonuria</em>, PubMed, viewed 1st February, 2011.<a href="http://www.ncbi.nlm.nih.gov/pubmed/6441863">http://www.ncbi.nlm.nih.gov/pubmed/6441863</a></li>

<li>Mathews-Larson, J., <em>Depression Free, Naturally</em>, Ballantine Publishing Group, 2001.</li>

<li>Walsh, W., <em>Commentary on Nutritional Treatment of Mental Disorders</em>, International Guide to the world of Alternative health, viewed 2nd Febraury, 2011.<a href="http://www.alternativementalhealth.com/articles/walsh.htm">http://www.alternativementalhealth.com/articles/walsh.htm</a></li>

<li>Stuckey, R., Walsh, W., Lambert, B., <em>The Effectiveness of Targeted Nutritional Therapy in the treatment of Mental Illness</em>, ACNEM Journal, Vol. 39, No. 3, November 2010.</li>

<li>Faber, S., Zinn, G, M., Kern, J, C., Kingston, H, M., 2009, <em>The plasma zinc/serum copper ratio as a biomarker in children with autism spectrum disorders</em>, PubMed, viewed 5th February, 2011.<a href="http://www.ncbi.nlm.nih.gov/pubmed/19280374">http://www.ncbi.nlm.nih.gov/pubmed/19280374</a></li>

<li>Jackson, J, A., Riordan, N, D., Neathery, S., Revard, C.,<em>Histamine Levels in Health and Disease</em>, Journal of Orthomolecular Medicine, Vol. 13, No. 4, 1998.</li>

<li>Hoffer, A. and Osmond, H., <em>Malvaria: A New Psychiatric Disease,</em> Acta Psychiatrica Scandanivica, 1963.</li>

<li>Pfeiffer, C.C. and Holford, P., <em>Mental Illness and Schizophrenia: the Nutritional Connection</em>, Harper Collins, 1987.</li>

<li>McGinnis, W.R., <em>Discerning the Mauve Factor Part 1 and 2</em>, In Press, 2007.</li>

<li>Hoffer, A., <em>The Discovery of Kryptopyrrole and it's importance in diagnosis of biochemical imbalances in Schizophrenia and in criminal behaviour</em>, Journal of Orthomolecular Medicine, 1995.</li>

<li>Cutler, M.G., Graham, D.J., and Moore, M.R., <em>The Mauve Factor of Porphyria, 3-ethyl-5-hydroxy-4,5-dimethyl-delta-3-pyrrolline-2-one: effects on behaviour of rats and mice,</em>Pharmacology & Toxicology, 1990.</li>

<li>Pfeiffer, C.C., Mailloux, R., and Forsythe, L., <em>The Schizophrenias: ours to conquer</em>, Biocommunications Press, 1988.</li>

<li>Irvine, D.G., <em>Pyrroles in Neuropyschiatric and Porphyric disorders: confirmation of a metabolite structure by synthesis</em>, Life Sci, 1978.</li>

<li>Campbell-McBride.N., <em>Gut and Psychology Syndrome</em>, Medinform Publishing, 2004.</li>

<li>McGinnis, W.R., 2004, <em>Pyroluria -</em> Hidden <em>Cause of Schizophrenia, Bipolar, Depression and Anxiety Symptoms</em>, International Guide to the World of Alternative Health, viewed 24th January 2011.<a href="http://www.alternativementalhealth.com/articles/pyroluria.htm">http://www.alternativementalhealth.com/articles/pyroluria.htm</a></li>

<li>Fredericks, C., <em>Nutrition Guide for the Prevention and Cure of Common Ailments and Diseases</em>, Simon & Schuster, NY, 1982.</li>

<li>Eck, P. and Wilson, L., <em>Toxic Metals in Human Health and Disease</em>, Eck INstutute of Applied Nutritiona and Bioenergetics, Ltd., Phoenix, AZ, 1989.</li>

<li>O Flaherty, E., <em>The Role of Gut in Mental Illness,</em> Irish Medical Times, Blackrock, Dublin.</li>

<li>Xie, X., Smart, T. G., <em>Properties of GABA-mediated synaptic potentials induced by zinc in adult rat hippocampal pyramidal neurones</em>, The Journal of Physiology, London, 1993. Viewed 10th October 2011<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1175226/">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1175226/</a></li>

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Hypercupremia - High Copper

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