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.
3. 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.
SELECTED
REFERENCES
1. Cunnane, S.C., Zinc: Clinical and
Biochemical Significance, CRC Press, Inc., Boca Raton, FL (1988).
2. 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.
3. 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.
4. 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.
5. 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).
6. Reding,
P., DuChateau, J., and Bataille, C., "Oral zinc supplementation improves
hepatic encephalopathy", Lancet, 1984; ii: 493.
