ZINC DEFICIENCY, METAL METABOLISM, AND BEHAVIOR DISORDERS

ZINC DEFICIENCY, METAL METABOLISM, AND BEHAVIOR DISORDERS by William J. Walsh INTRODUCTION Most Americans receive all the zinc they need if they have a reasonably well-balanced diet involving the major food groups. However, many persons are born with a metal-metabolism disorder which results in zinc depletion regardless of diet. Zinc is a component of more than 80 enzymes. High concentrations have been found in brain hippocampus, and many medical researchers believe that zinc is a neurotransmitter. Low zinc levels at these sites could reduce the inhibition of neuron activity, thus leading to abnormal behavior. The discovery of zinc "finger proteins" in the past decade has led to a vastly improved understanding of how cells replicate and divide. There role in behavior is not yet clear, but could be involved in the transport or availability of zinc. Recent research has shown zinc to be far more important than previously believed and low levels of zinc are associated with behavior disorders. Many of the patients of the Carl Pfeiffer Treatment Center suffer from behavior disorders. The most common ones are attention deficit hyperactive disorder (ADHD), oppositional defiant disorder (ODD), obsessive compulsive disorder (OCD), and conduct disorder (CD). These patients typically have a history of extensive counseling and multiple medications and many have experienced residential care. They represent a narrow and rather uncharacteristic segment of the general population. A high percentage of behavior disordered persons exhibit abnormal levels of copper, zinc, lead, cadmium, calcium, magnesium and manganese in blood, urine, and tissues, based on chemical analysis results from thousands of patients. With regard to zinc, this condition appears to involve a malfunction of the metal-binding protein metallothionein. Most of these patients have symptoms of zinc deficiency along with depressed levels of zinc in their blood plasma. The high incidence of zinc deficiency in assaultive young males was illustrated in a recent study1 which found elevated serum copper and depressed plasma zinc concentration, compared to normal controls. This study confirmed our clinical observations of zinc depletion in more than 4,000 behavior disordered patients. Our clinical observations and research have indicated that the copper/zinc ratio appears to be more decisively important than either of the individual metals alone. Zinc deficiency often results in elevated blood levels of copper, due to the dynamic competition of these metals in the body. Elevated blood copper has been associated with episodic violence, hyperactivity, learning disabilities, and depression. DIAGNOSIS OF ZINC DEFICIENCY Zinc deficiency is difficult to diagnose since no single laboratory test or combination of tests is decisive in every case. For example, blood levels are sometimes normal in zinc deficient persons due to homeostasis. Urine and hair tissue levels are often elevated in zinc deficiency because of "short circuiting" of zinc through the body and high rates of excretion. The two principal factors which lead our Center's physicians to a diagnosis of zinc deficiency are: 1) depressed plasma zinc, and 2) presence of clinical symptoms of zinc depletion which are alleviated by zinc supplementation2, 3, 4, 5, 6, and 7. Since zinc tolerance tests show plasma levels to be affected for 6 hours following zinc supplementation8 and 9, zinc supplements are avoided for 24 hours prior to sampling of plasma. The clinical symptoms associated with zinc deficiency or depletion include the following: * Eczema, acne, and/or psoriasis10, 11, 12, 13, and 14, * Poor wound healing, including leg ulcers and oral lesions15 and 16, * Lines of Beau on the fingernails17, * Growth retardation18, 19, 20, and 21, * Delayed sexual maturation22, * Hypogeusia or poor taste acuity23 and 24, and * Chronic immunodeficiency and frequent infections25 and 26. A "working diagnosis" of zinc deficiency can be made if clinical symptoms of zinc deficiency are clearly evident from the initial physical examination and medical history. Usually more than one or the above symptoms are present in zinc deficiency. This initial diagnosis is later supported or negated by laboratory analysis for plasma zinc along with observed response (or non-response) to zinc supplementation. The Carl Pfeiffer Treatment Center generally retests plasma zinc and evaluates symptoms after 4-6 months of treatment to determine if dosages need adjustment. TREATMENT OF ZINC DEPLETION Zinc depletion is corrected by supplementation with zinc (picolinate or gluconate) along with augmenting nutrients including L-cysteine, pyridoxine, ascorbic acid, and vitamin E. Manganese is also useful in promoting proper metallothionein function. If copper levels are elevated, effective treatment must also enhance the release of copper from tissues and copper excretion. L-cysteine helps mobilize and excrete copper while enhancing zinc absorption. Correction of zinc deficiency is best accomplished under the care of a physician or nutritionist who is experienced in metal metabolism disorders. Indiscriminant dosages of zinc to persons who do not need it can cause anemia and imbalanced trace metals. Treatment of mild or moderate zinc depletion can take months to complete. Some cases of severe zinc depletion require a year or more to resolve. Achievement of a proper zinc balance is slowed by growth spurts, injury, illness, or severe stress. In addition, persons with malabsorption or Type A blood respond to treatment more slowly. DISCUSSION We find that zinc deficient individuals usually respond well to inexpensive supplementation with zinc and augmenting nutrients. Many patients who previously experienced years of counseling, psychotherapy, aggressive medication programs, and/or residential treatment become greatly improved and respond to less intensive (and less expensive) therapies. Zinc deficiency can be corrected, but not cured. If treatment is discontinued, the prior zinc deficiency will reemerge with all symptoms gradually returning. Zinc deficiency, like diabetes, requires life long treatment. Fortunately, it is a simple, low cost, safe treatment. The Center involves the collaboration of biochemists and medical doctors. We believe that this coupling of disciplines provides an ideal capability for biochemical evaluation and medical treatment. REFERENCES 1. Walsh, W.J., Isaacson, H.R., Rahman, F., Hall, A., and Young, I.J., "Elevated blood copper:zinc ratios in assaultive young males", Neuroscience Annual Meeting, Abstract of Papers, Miami Beach, 1994 (In Print). 2. Cunnane, S.C., Zinc: Clinical and Biochemical Significance, CRC Press, Inc., Boca Raton, FL (1988). 3. Prasad, A.S., "Deficiency of zinc in man and its toxicity", in Trace Elements in Human Health and Disease, Vol. 1, Academic Press, New York, 1976. 4. Prasad, A.S., "Clinical and biochemical spectrum of zinc deficiency in human subjects", in Current Topics in Nutrition and Disease, Vol 6, New York, 1982. 5. Smith, J.C., Holbrook, J.T., and Danford, D.E., "Analysis and evaluation of zinc and copper in human plasma and serum", J. Amer. College of Nutr., 4:627-638 (1985). 6. Kleimola, V., et al, "The zinc, copper, and iron status in children with chronic diseases", in Trace Element Analytical Chemistry in Medicine and Biology, Walter de Gruyter, New York (1983). 7. Reding, P., DuChateau, J., and Bataille, C., "Oral zinc supplementation improves hepatic encephalopathy", Lancet, ii, 493 (1984). 8. Pohit, J., Saha, K.C., and Pal, B., "A zinc tolerance test", Clin. Chim. Acta, 114: 279 (1981). 9. Pecoud, A., Donzel, P., and Schelling, J.L., "Effects of foodstuffs on the absorption of zinc sulphate", Clin. Pharmacol. Ther., 17, 469 (1975). 10. Molokhia, M.M. and Portnoy, B., "Zinc and copper in dermatology", in Zinc and Copper in Medicine, Charles C. Thomas, Springfield, IL (1980). 11. Schmidt, K., et.al., "Determination of trace element concentrations in psoriatic and non-psoriatic scales with special attention to zinc", in Trace Element Analytical Chemistry in Medicine and Biology, Vol. 1, Walter de Gruyter, New York (1980). 12. McMillan, E.M., and Rowe, D., "Plasma zinc in psoriasis. Relation to surface area involvement", Br. J. Dermatol., 108, 301 (1983). 13. Ecker, R.J. and Schroeder, A.L., "Acrodermatitis and acquired zinc deficiency", Arch. Dermatol., 114: 937 (1978). 14. Withers, A.F., Baker, H., and Musa, M, "Plasma zinc in psoriasis", Lancet, ii: 278 (1968). 15. Van Rij, A.M., "Zinc supplements in surgery", in Zinc and Copper in Medicine, Charles C. Thomas, Springfield, IL (1982). 16. Henzel, J.H., et al., "Zinc concentrations within healing wounds: significance of post-operative zincuria on availability and requirements during tissue repair", Arch. Surg., 349: 357 (1970). 17. Weismann, K., "Lines of Beau: Possible markers of zinc deficiency", Acta Dermatol. Venereol., 57: 88 (1977). 18. Collipp, P.J., et al., "Zinc deficiency: Improvement in growth and growth hormone levels with oral zinc therapy", Ann. Nutr. Metab., 26: 287 (1982). 19. Hambridge, K.M., and Walravens, P.A., "Zinc deficiency in infants and preadolescent children", in Trace Elements in Human Health and Disease, Vol. 1, Prasad, A.S. and Oberleas, D., Eds., Academic Press, New York (1976). 20. Golden, B.E. and Golden, M.H.N., "Effect of zinc supplementation on the dietary intake, rate of weight gain and energy cost of tissue deposition in children recovering from severe malnutrition", Am. J. Clin. Nutr., 34: 900 (1981). 21. Laditan, A.O. and Ette, S.I., "Plasma zinc and copper during the acute phase of protein-energy malnutrition (PEM) and after recovery", Trop. Geogr. Med., 34: 77 (1982). 22. Sandstead, H.H., Prasad, A.S., et al., "Human zinc deficiency, endocrine manifestations, and response to treatment", Amer. J. Clin. Nutr., 20:422 (1967). 23. Heinkin, R.I., and Bradley, D.F., "Hypogeusia corrected by nickel and zinc", Life Sci., 9: 701 (1970). 24. Sprenger, K.B.G. et al., "Improvement of uremic neuropathy and hypogeusia by dialysate zinc supplementation: a double-blind study", Kidney Int., Suppl. 16: 5315 (1983). 25. Cunningham-Rundles, C., et al., "Zinc deficiency, depressed thymic hormones and T-lymphocyte dysfunction in patients with hypogammaglobulinemia", Clin. Immunol. Immunopathol., 21: 387 (1981). 26. Good, R.A., et al., "Zinc and immunity", in Clinical, Biochemical, and Nutritional Aspects of Trace Elements, Prasad, A.S. Ed., Alan R. Liss, New York (1982). Health Research Institute Pfeiffer Treatment Center HRI Pharmacy 4575 Weaver Parkway - Warrenville, IL 60555-4039 (630) 505-0300 - (630) 836-0667 fax Questions or Comments:info@HRIPTC.org | Home Page | Services | Pharmacy | Research | Education | Patient Info | Directions | All contents Copyright (c) 2004 Health Research Institute. All rights reserved. HRI is a Not-for-Profit 501c3.