Nutritional Deficiencies - Health Concerns

Zinc - updated: 01 December 2008

Clinical manifestations of zinc deficiency

Annu Rev Nutr. 1985;5:341-63

Prasad AS.

The essentiality of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, chronic renal diseases, following uses of certain drugs such as penicillamine for Wilson's disease and diuretics in some cases, and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. In pregnancy and during periods of growth the requirement of zinc is increased. The clinical manifestations in severe cases of zinc deficiency include bullous-pustular dermatitis, alopecia, diarrhea, emotional disorder, weight loss, intercurrent infections, hypogonadism in males; it is fatal if unrecognized and untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities, and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss, and hyperammonemia. Zinc is a growth factor. Its deficiency adversely affects growth in many animal species and humans. Inasmuch as zinc is needed for protein and DNA synthesis and for cell division, it is believed that the growth effect of zinc is related to its effect on protein synthesis. Whether or not zinc is required for the metabolism of somatomedin needs to be investigated in the future. Testicular functions are affected adversely as a result of zinc deficiency in both humans and experimental animals. This effect of zinc is at the end organ level; the hypothalamic-pituitary axis is intact in zinc-deficient subjects. Inasmuch as zinc is intimately involved in cell division, its deficiency may adversely affect testicular size and thus affect its functions. Zinc is required for the functions of several enzymes and whether or not it has an enzymatic role in steroidogenesis is not known at present. Thymopoeitin, a hormone needed for T-cell maturation, has also been shown to be zinc dependent. Zinc deficiency affects T-cell functions and chemotaxis adversely. Disorders of cell-mediated immune functions are commonly observed in patients with zinc deficiency. Zinc is beneficial for wound healing in zinc-deficient subjects. In certain zinc-deficient subjects, abnormal taste and abnormal dark adaptation have been noted to reverse with zinc supplementation.

Publication Types:

• Review

Zinc nutrition and growth retardation

Cole CR, Lifshitz F.

Human growth retardation from zinc deficiency was first reported over 40 years ago. More recently marginal zinc deficiency was shown to occur during pregnancy and infancy, and to be prevalent in children throughout the world. Zinc with or without macronutrients and other micronutrient deficits may also occur in patients with gastrointestinal disease. Particular attention must be given to the suboptimal intake of zinc which results in growth retardation. The single most important cause of nutritional growth retardation (NGR) worldwide is poverty related malnutrition involving multiple macro-and-micro nutrient deficits. NGR is an underappreciated entity in pediatric endocrine clinics since these patients do not manifest clinical evidence of malnutrition or overt nutrient deficits. A deceleration in body weight progression and decreased growth rates are the only clinical manifestations of the altered nutrient status. The growth deceleration occurs as an adaptive response to suboptimal nutrition to maintain equilibrium between genetic growth potential and nutritional intake. However the potential effects of suboptimal zinc intake in patients with NGR may be difficult to assess as there are no good clinical markers pertaining to this mineral. Zinc is known to be an essential micronutrient involved in growth, though the mechanism(s) by which zinc deficiency impairs growth has not been elucidated. Several hundred zinc-containing nucleoproteins are involved in gene expression of multiple proteins, many of them are important for growth. Zinc deficiency reduces IGF-I production, and may decrease cellular IGF-responsiveness. This may explain why the zinc status of GH deficient children significantly affects their response to GH treatment. In experimental models mild restriction of energy appeared to be more important in regard to growth retardation than suboptimal zinc intake, and the simultaneous restriction of energy and zinc did not augment the growth deterioration of chronic suboptimal nutrition. The USDA food guide is a simple guideline which should serve the needs of pediatric endocrinologists when evaluating the quality of the dietary intake of a short child and to provide guidelines for food intake to the patients.

Publication Types:

• Review

Zinc involvements in the brain

Rev Med Chir Soc Med Nat Iasi. 2007 Oct-Dec;111(4):981-5

Ciubotariu D, Nechifor M.

Central nervous system (CNS) concentrates almost 10% of total zinc in the human body. Imbalances in zinc concentration are associated with numerous CNS diseases. Zinc deficiency is associated with nervous anorexia, major depression, cognitive impairment, and uncontrolled behavior. Our data reveal that plasma zinc concentration is decreased in major depression and it significantly increases following sertraline or amitriptyline treatment. Also, we found that ZnCl2 administration while inducing morphine-dependence in rats significantly decreases the symptoms of opioid-withdrawal syndrome. Recent data incriminate zinc deficit in the development of encephalopathy following severe impairment of hepatic function. On the other hand, zinc content of certain brain areas in Alzheimer disease is twice that in controls. Parkinson disease is also associated with higher zinc concentrations in the brain than normal. The ratio plasma zinc- other bivalent cations is also important for normal brain function.

Publication Types:

• Review

Zinc in human health: effect of zinc on immune cells

Mol Med. 2008 May-Jun;14(5-6):353-7

Prasad AS.

Although the essentiality of zinc for plants and animals has been known for many decades, the essentiality of zinc for humans was recognized only 40 years ago in the Middle East. The zinc-deficient patients had severe immune dysfunctions, inasmuch as they died of intercurrent infections by the time they were 25 years of age. In our studies in an experimental human model of zinc deficiency, we documented decreased serum testosterone level, oligospermia, severe immune dysfunctions mainly affecting T helper cells, hyperammonemia, neurosensory disorders, and decreased lean body mass. It appears that zinc deficiency is prevalent in the developing world and as many as two billion subjects may be growth retarded due to zinc deficiency. Besides growth retardation and immune dysfunctions, cognitive impairment due to zinc deficiency also has been reported recently. Our studies in the cell culture models showed that the activation of many zinc-dependent enzymes and transcription factors were adversely affected due to zinc deficiency. In HUT-78 (T helper 0 [Th(0)] cell line), we showed that a decrease in gene expression of interleukin-2 (IL-2) and IL-2 receptor alpha(IL-2Ralpha) were due to decreased activation of nuclear factor-kappaB (NF-kappaB) in zinc deficient cells. Decreased NF-kappaB activation in HUT-78 due to zinc deficiency was due to decreased binding of NF-kappaB to DNA, decreased level of NF-kappaB p105 (the precursor of NF-kappaB p50) mRNA, decreased kappaB inhibitory protein (IkappaB) phosphorylation, and decreased Ikappa kappa. These effects of zinc were cell specific. Zinc also is an antioxidant and has anti-inflammatory actions. The therapeutic roles of zinc in acute infantile diarrhea, acrodermatitis enteropathica, prevention of blindness in patients with age-related macular degeneration, and treatment of common cold with zinc have been reported. In HL-60 cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A20 mRNA, which, via TRAF pathway, decreases NF-kappaB activation, leading to decreased gene expression and generation of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-8. We have reported recently that in both young adults and elderly subjects, zinc supplementation decreased oxidative stress markers and generation of inflammatory cytokines.

Publication Types:

• Review

Zinc: mechanisms of host defense

J Nutr. 2007 May;137(5):1345-9

Zinc deficiency in humans decreases the activity of serum thymulin (a thymic hormone), which is required for maturation of T-helper cells. T-helper 1 (Th(1)) cytokines are decreased but T-helper 2 (Th(2)) cytokines are not affected by zinc deficiency in humans. This shift of Th(1) to Th(2) function results in cell-mediated immune dysfunction. Because IL-2 production (Th(1) cytokine) is decreased, this leads to decreased activities of natural-killer cell and T cytolytic cells, which are involved in killing viruses, bacteria, and tumor cells. In humans, zinc deficiency may decrease the generation of new CD4+ T cells from the thymus. In cell culture studies (HUT-78, a Th(0) human malignant lymphoblastoid cell line), as a result of zinc deficiency, nuclear factor-kappaB (NF-kappaB) activation, phosphorylation of IkappaB, and binding of NF-kappaB to DNA are decreased and this results in decreased Th(1) cytokine production. In another study, zinc supplementation to humans decreased the gene expression and production of pro-inflammatory cytokines and decreased oxidative stress markers. In HL-60 cells (a human pro-myelocytic leukemia cell line), zinc deficiency increased the levels of TNF-alpha, IL-1beta, and IL-8 cytokines and mRNA. In these cells, zinc induced A20, a zinc finger protein that inhibited NF-kappaB activation via tumor necrosis factor receptor associated factor pathway, and this decreased gene expression of pro-inflammatory cytokines and oxidative stress markers. We conclude that zinc has an important role in cell-mediated immune functions and also functions as antiinflammatory and antioxidant agent.

Publication Types:

• Review

Zinc and immunity

Mol Cell Biochem. 1998 Nov;188(1-2):63-9

Prasad AS.

Nutritional deficiency of zinc is widespread throughout the developing countries and a conditioned deficiency of zinc is known to occur in many diseased states. Zinc is known to play an important role in the immune system and zinc deficient subjects may experience increased susceptibility to a variety of pathogens. We have studied the effects of a mild deficiency of zinc on T cells in an experimental model of human zinc deficiency. We showed that T cell functions were affected adversely even when the deficiency of zinc was mild in humans. Characteristically during zinc deficiency, the serum thymulin activity (a thymic hormone) was decreased which was restored following zinc supplementation. Our studies also showed that zinc deficiency caused an imbalance between TH1 and TH2 functions. The production of IFN-g, IL-2, TNF-a (products of TH1 cells) were decreased, whereas the production of IL-4, IL-6 and IL-10 (products of TH2) were not affected during zinc deficiency. T cell subpopulation studies revealed that the CD4+ CD45RA+ to CD4+ CD45RO+ ratio was decreased as a result of zinc deficiency, suggesting that zinc may be required for the regeneration of new CD4+ T cells. We further documented that zinc deficiency decreased NK cell lytic activity and caused a decrease in the percentage of CD8+ CD73+ T cells which are known to be predominantly precursors of cytotoxic T cells. In a suitable cell culture model our studies revealed that the gene expression of a DNA synthesizing enzyme TK was affected adversely which resulted in delayed cell cycle and decreased cell growth. The above immunological consequences of zinc deficiency may be responsible for decreased cell mediated immune functions in zinc deficient subjects.

Publication Types:

• Review

Functional consequences of zinc deficiency

Prog Food Nutr Sci. 1985;9(1-2):185-226

McClain CJ, Kasarskis EJ Jr, Allen JJ.

Zinc is an essential trace element necessary for over 200 zinc metalloenzymes and required for normal nucleic acid, protein, and membrane metabolism. During the past two decades there has been a rapid expansion of knowledge concerning zinc metabolism in both normal and disease situations, including mechanisms for zinc absorption, excretion and internal redistribution of zinc after stress or trauma. Acrodermatitis enteropathica has been recognized to be a disease of impaired zinc absorption in man. A host of disease processes now are recognized to be complicated by zinc deficiency including alcoholic liver disease, sickle cell anemia, protein calorie malnutrition, and a variety of intestinal diseases including Crohn's disease, sprue, short bowel syndrome and after jejunal ileal bypass. Zinc has proved to be an extremely interesting mineral to nutritionists and physicians because of its importance in normal physiology and biochemistry and because of the diverse presenting features of zinc deficiency. This paper reviews ten functional consequences of zinc deficiency and emphasizes certain consequences in which there have been new discoveries concerning their mechanism (e.g., anorexia) or their clinical importance (e.g., immune dysfunction).

Publication Types:

• Review

Publication Types:

• Review