ZINC DEFICIENCY and METABOLISM
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. Zinc deficiency can result in irritability, anger episodes, impaired immune function, acne, stunting of growth, poor taste and smell sensitivity, and impaired wound healing. There is a high incidence of zinc deficiency in people labeled with ADD, autism, depression, schizophrenia, eating disorders and bipolar disorders.
The discovery of zinc “finger proteins” in the past decade has led to a vastly improved understanding of how cells replicate and divide. The role of these proteins in behavior is not yet clarified. Zinc is far more important than often recognized, and low levels of zinc are associated with behavior disorders.
Zinc is found in the highest concentration in the middle ear and cochlea, the eye, the brain, and in the prostate and sperm.
A large percentage of behavior disordered persons exhibit abnormal levels of copper, zinc, lead, cadmium, calcium, magnesium and manganese in blood, urine, and tissues. This 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 found in a study by WJ Walsh presented at the Neuroscience Annual Meeting in 1994. He found elevated serum copper and depressed
plasma zinc concentration, compared to normal controls. This study confirmed the clinical observations of
the Pfeiffer Treatment Center showing zinc depletion in more than 4,000 behavior disordered patients.
Clinical observations and research indicate the copper/zinc ratio appears to be more important than either copper or zinc levels 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. Zinc is antagonistic to cadmium, lead, and mercury.
Zinc deficiency is hard to confirm since no single laboratory test is always low. 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 demand for zinc increases under psychological and physiological stress.
Four principal factors support a diagnosis of zinc deficiency:
Depressed blood level (plasma or red cell) zinc. Since zinc tolerance tests show plasma levels to be affected for six hours following zinc supplementation (Pohit J, “A zinc tolerance test”, Clin. Chim. Acta, 1981;114:279 and Pecoud A “Effects of foodstuffs on the absorption of zinc sulfate”, Clin. Pharmacol. Ther., 1975:17: 469), zinc supplements are avoided for 24 hours prior to sampling of plasma. The optimal range of plasma zinc is 90-150 mcg/dl.
Clinical symptoms compatible with zinc depletion.
* Eczema, acne, and/or psoriasis (Molokhia MM, “Zinc and copper in dermatology”, in Zinc and Copper in Medicine, Charles C. Thomas, Springfield, IL (1980), 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), McMillan EM, “Plasma zinc in psoriasis. Relation to surface area involvement”, Br. J. Dermatol. 1983;108:301, Ecker RJ, “Acrodermatitis and acquired zinc deficiency”, Arch. Dermatol., 1978;114: 937 and Withers AF, “Plasma zinc in psoriasis”, Lancet, 1968;ii)
* Poor wound healing, including leg ulcers and oral lesions (Van Rij AM., “Zinc supplements in surgery”, in Zinc and Copper in Medicine, Charles C. Thomas, Springfield, IL (1982) and Henzel JH, et al., “Zinc concentrations within healing wounds: significance of post-operative zincuria on availability and requirements during tissue repair”, Arch. Surg. 1970;349:357)
* Lines of Beau on the fingernails (Weismann, K., “Lines of Beau: Possible markers of zinc deficiency”, Acta Dermatol. Venereol. 1977;57: 88)
* Growth retardation (Collipp PJ., et al., “Zinc deficiency: Improvement in growth and growth hormone levels with oral zinc therapy”, Ann. Nutr. Metab. 1982;26:287, Hambridge KM, “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), Golden BE, “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.1981;34:900 and Laditan AO, “Plasma zinc and copper during the acute phase of protein-energy malnutrition (PEM) and after recovery”, Trop. Geogr. Med. 1982;34:77).
* Delayed sexual maturation (Sandstead HH, et al., “Human zinc deficiency, endocrine manifestations, and response to treatment”, Amer. J. Clin. Nutr., 1967;20:422 )
* Poor taste acuity/ability (Heinkin, R.I., and Bradley, D.F., “Hypogeusia corrected by nickel and zinc”, Life Sci., 1970; 9:701 and Sprenger KBG. et al., “Improvement of uremic neuropathy and hypogeusia by dialysate zinc supplementation: a double-blind study”, Kidney Int., 1983;Suppl 16: 5315)
* Chronic immunodeficiency and frequent infections (Cunningham-Rundles, C., et al., “Zinc deficiency, depressed thymic hormones and T-lymphocyte dysfunction in patients with hypogammaglobulinemia”, Clin. Immunol. Immunopathology, 1981;21:387 and Good RA, et al., “Zinc and immunity”, in Clinical, Biochemical, and Nutritional Aspects of Trace Elements, Prasad, A.S. Ed., Alan R. Liss, New York (1982).
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. Behavioral problems and pyroluria should also raise suspicion of zinc deficiency.
Laboratory imbalances that are associated with zinc insufficiency such as elevated carnosine/histidine ratio, phosphoserine, and phosphethanolamine or low levels of leucine, isoleucine, valine, and histidine.
Improvement with zinc supplementation. This initial diagnosis is later supported or negated by laboratory analysis for zinc along with observed response (or non-response) to zinc supplementation. Generally a retest for zinc along with clinical evaluation of symptoms is done after 4-6 months of treatment to determine if dosages need adjustment.
Zinc depletion is corrected by supplementation with specific forms of zinc along with supporting nutrients. Correction of zinc deficiency is best accomplished under the care of a physician or nutritionist who is experienced in metal metabolism disorders. Zinc toxicity is associated with gastrointestinal irritation, vomiting, changes in HDL and LDL cholesterol ratios, copper deficiency and impaired immunity. Indiscriminant dosages of zinc to persons who do not need it can cause anemia and imbalanced trace metals.
Absorption of dietary zinc into the bloodstream is usually about 35-45% efficient, but malabsorption syndromes can reduce zinc uptake to about 10-15%. Once in the bloodstream, zinc concentrations are controlled by the metal-binding protein, metallothionein. Many persons with zinc deficiency appear to have a metallothionein disorder. Patients with an overproduction of pyroles (pyroluria) also develop zinc deficiencies.
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.
The average American typically consumes 10mg of zinc a day which is one third less than the RDA.
Zinc deficient individuals usually respond well to supplementation. 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, zinc deficiency usually will reemerge with all symptoms gradually returning. Zinc deficiency, like diabetes, requires life long treatment.
Cunnane, S.C., Zinc: Clinical and Biochemical Significance, CRC Press, Inc., Boca Raton, FL (1988).
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.
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.
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 Nutrition. 1985;4:627-638.
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).
Reding, P., DuChateau, J., and Bataille, C., “Oral zinc supplementation improves hepatic encephalopathy”, Lancet, 1984; ii: 493.