Zinc depletion can cause dermatological problems, skin lesions, acne and weight loss. Alkaline phosphatase levels are depressed with zinc depletion but levels rise quickly with zinc supplements.
Zinc depletion studies have allowed researchers to piece together the physiological consequences of low zinc intakes. Zinc metabolism is highly complex, and the study of zinc is made more difficult by the wide variety of proteins that it associates with in animals. For example in humans, zinc is known to be a cofactor for more enzymes than all the other essential minerals combined. Zinc has many divergent functions in human nutrition and this includes a role that provide structural rigidity to enzymes, as well as direct participation in reactions through binding at the catalytic site. In this regard zinc represents enzymes from every class including oxidoreductase, hydrolase, lyase, isomerase, transferase and ligase enzymes. One role that is particularly well known for zinc is as a cofactor in synthetic processes. Zinc depletion may therefore be expected to affect protein synthesis, nitrogen retention and cause changes in levels of serum proteins such as albumin, transferrin and retinol binding protein. Further, cells with rapid turnovers such as lymphocytes and hair root cells may also be affected by zinc depletion.
The effects of zinc depletion have been investigated in healthy subjects using controlled conditions in metabolic units. In one study1 subjects were fed a zinc depletion diet of 0.28mg per day zinc to produce plasma levels below 70 μg per 100 g. The zinc depletion period produced mild to severe clinical symptoms in the subjects which included most commonly dermatological changes, diarrhea, sore throat and headaches. In some subjects these were mild, but in others several patches of dry skin and scalp as well as acne developed. One subject had such severe reactions that medical intervention was required but zinc supplementation quickly reversed all symptoms. All subjects began to lose weight and so energy intake was increased to prevent appreciable weight loss. Interestingly, the authors noted that when the subject who received medical attention was repleted with zinc, he gained weight despite his calorie intake decreasing, which the authors thought was important enough to highlight in italics.
Alkaline phosphatase is an enzyme that requires four zinc atoms for its function, which is to remove phosphate groups from a variety of molecules. During zinc depletion levels of alkaline phosphatase decreased significantly in the subjects, and these levels recovered during the repletion phase. The lowering of plasma alkaline phosphatase with zinc depletion has been reported in other studies2, and has been shown to respond well to oral supplements or parenteral nutritional. Supplementation of non-zinc depleted subjects however tends to decrease alkaline phosphatase plasma levels. Alkaline phosphatase may therefore be a good marker for zinc deficiency as increases with supplementation likely define the zinc depleted state. Many animal experiments have shown that depressed levels of plasma alkaline phosphatase are been able to be restored rapidly through zinc supplementation. However, response of bone, leukocyte, intestinal and liver alkaline phosphatase to zinc supplements are not as well understood.
Other effects from zinc depletion have been reported but biochemical individuality seems to determine the exact response of each individual. Inflammation of the buccal cavity which may be related to the development of sore throats, have been reported in cases of zinc depletion. In addition, as shift from the growing anagen phase of hair roots to the resting telogen phase occurs as zinc depletion proceeds. Significant increases in area under the curve for glucose also occurs in some subjects suggesting that insulin sensitivity may deteriorate. Changes is other zinc enzymes are also present in cases of zinc depletion, but the changes are inconsistent between subjects, suggesting that other factors may be involved as the causative agent. Weight loss is also present in many cases of zinc depletion, and a loss of appetite is an often reported and well known symptom of zinc deficiency. The low intakes of zinc in the Western diet suggest that unexplained sub-clinical symptom may be caused in some cases by long term zinc depletion.
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