Zinc is an essential trace element, stored mainly in muscle. Most circulating zinc, some 80%, is present in the red cells. A similar proportion of plasma zinc is albumin bound. Most of the remaining plasma zinc is bound to alpha-2 macroglobin, although a small percentage is present as amino acid complexes.
Zinc is a component of many enzymes and other protein structures (eg the zinc finger, as in transcription activation factors). Thus zinc is crucial for normal growth and maturation; in malnourished children, the rate of recovery of lean body mass is related to dietary zinc intake. Zinc is regulated through its uptake by intestinal mucosa in processes depending on intracellular zinc binding proteins, the mechanisms of which are not fully understood. Significant interactions with other trace elements, especially iron and copper occur. Zinc supplementation can result in copper deficiency and vice versa; the efficiency of absorption of both zinc and iron depend on the ratio in which they are present.
Deficiency
Frank zinc deficiency was originally identified as the cause of anaemia, growth retardation and hypogonadism in deprived populations in the third world. Dramatic loss of zinc may occur during catabolic processes, following operations, or severe infections; acute zinc deficiency may then be precipitated as anabolic processes requiring zinc supervene. This has been well documented in patients on TPN with inadequate supplementation; the symptoms include a characteristic rash, abdominal pain and diarrhoea with depression and lethargy. Acrodermatitis enteropathica is a rare, autosomal, recessive inherited defect of zinc absorption, which presents with similar symptoms shortly after weaning. Lifelong therapy with large doses of zinc is effective. Zinc deficiency (and/or copper deficiency) may occur in premature infants prior to weaning, precipitated by interrupted feeding or increased requirements (such as an infection), when maternal milk concentrations of these elements are low. Premature infants are at risk because they have smaller accumulated stores at birth. The reversal of symptoms on treatment is dramatic. Many situations have been described in which plasma zinc is low and marginal deficiency has been postulated. The exact significance of the findings is not always clear, as plasma zinc is affected by many factors such as diet, diurnal variation, binding properties of albumin, acute phase response, steroid therapy, and pregnancy. Nevertheless, marginal zinc deficiency has been demonstrated in some situations and may be more widespread than is generally thought.
Laboratory Indices of Zinc Status
Serum zinc assay is the simplest means of assessing zinc status, but concentrations vary for many reasons unconnected with zinc nutriture. There is a diurnal variation with peak values about 10.00 h. Large fluctuations occur after meals and fasting leads to an increase. Low values are found in pregnancy, in certain malignancies (e.g. leukaemia), in patients with renal failure, and when the serum albumin concentration is low. In situations of stress or infection, the actions of interleukin and steroids stimulate entry of zinc into cells and increased production of caeruloplasmin by the liver. The degree of any acute phase response expected should be borne in mind when interpreting low serum zinc concentrations; marginally low values are hard to interpret, but a concentration below 7 µmol/L indicates marked deficiency.
Urinary zinc excretion is also difficult to interpret; low excretion may indicate zinc deficiency, but raised or normal values do not exclude the possibility. Zinc is excreted when substances to which it can bind are excreted in the urine, such as organic acids, amino acids, low molecular weight proteins or certain drugs. In catabolic states, large amounts of zinc released from tissues may be excreted in the urine, giving rise to marked depletion at the recovery stage.
When zinc deficiency is present, a relatively low serum alkaline phosphatase activity is indicative, since the enzyme contains zinc; blood ammonia may also be slightly increased. Erythrocyte zinc responds only slowly to changes in zinc status, which are often rapid. This investigation may, however, be useful to differntiate between pre-existing thyrotoxicosis and transient hyperthyroidism during pregnancy. Leucocyte zinc content may offer an improved indication of zinc status as it correlates well with muscle zinc content. The test however, requires a large sample of blood, needing particularly careful handling soon after collection.
Zinc is a common element and precautions against contamination must always be maintained; collection tubes should be checked and kept covered; containers with metal or rubber closures or separating beads must be avoided, as should powder in gloves.
Assessment of altered taste perception by zinc ‘taste tests’ is unfortunately very subjective and is of no value in studies of zinc status.
References:
Lao TTH, Chin RKH, Swaminathan R, Panesar NS, Cockram CS. Erythrocyte zinc in differential diagnosis of hyperthyroidism in pregnancy: a preliminary report. BMJ 1987; 294: 1064-5
Vallee BL, Falchuk KH. The biochemical basis of zinc physiology. Physiol Revs 1993; 73: 79-118
Rhodes D, Kluh A. Zinc fingers. Scientific American February 1993: 56-65
Taylor A. Detection and monitoring for disorders of essential trace elements. Annals of Clinical Biochemistry 1996; 33: 486-510