Zinc is also important in the production of hormone like substances called prostaglandins (PGs). PGs are vital to numerous body functions including:
• the function of the immune system
• the expression and control of inflammation
• skin and wound healing
• functions of the heart and cardiovascular system
• absorption of various minerals
• body temperature control
• the important functions of fertility, conception, and delivery of the infant.
The way in which zinc influences PG production is by supporting the function of the enzymes which permit the conversion of the polyunsaturated fatty acids into PGs. The action of zinc is very direct in stimulating the normal production of PGs thereby maintaining or restoring normal health and fitness.
Zinc deficiency can result in many symptoms including: loss of appetite, growth retardation, diarrhea, tremor, hair loss, dandruff, a dry skin rash, white lines on fingernails, increased allergic sensitivity, disturbance of menstrual periods, pre-menstrual syndrome, delay of wound healing, loss of taste or smell sensation, dyslexia, poor night vision, photophobia (sensitivity to light), depression, sleep disturbance, hyperactivity, reduced fertility, loss of sex drive, pre-eclampsia (toxemia) of pregnancy and post-natal depression.
It has been observed that those suffering with any of the auto-immune diseases (such as multiple sclerosis, rheumatoid arthritis or psoriasis), atopic problems (allergy, eczema, asthma or migraine), or many of the inflammatory diseases (such as osteoarthritis or irritable bowel syndrome) have a consistent, and often severe, zinc deficiency which is greatly benefited by zinc replacement therapy.
The zinc taste test is used to evaluate this common state of deficiency. This simple and non-toxic test was devised and developed by Professor Derek Bryce-Smith, Professor of Biochemistry at Reading University. Professor Bryce Smith is an established authority on zinc and numerous other biochemical topics.
The test solution is zinc sulfate in purified water at a concentration of 2.5 gm/10ml. The test is based on the knowledge that the functions of taste and smell are dependent upon there being sufficient zinc available in the body. Therefore, if zinc is deficient, then taste function will be diminished. This principle is utilized in the taste test by offering a standard test solution of zinc sulfate for tasting.
The Zinc Taste Test (ZTT) is a valid assessment of patient zinc status with a basis in biochemistry. In 1981 Shatzman and Henkin published results of their research regarding gustin concentration in patients with hypogeusia in the Proc Natl. Acad. Sci., Vol. 78, No 6, pp. 3867-3871, June. Gustin is a zinc dependent polypeptide found in saliva that is thought to be a taste bud growth factor. These researchers found saliva gustin levels in patients with hypogeusia to be as low as 1/5 that of controls! These patients exhibited maximal changes in taste acuity after 12 days of zinc sulfate supplementation. In 1984 information appeared in the Lancet (Aug 11, p. 350; Nov 17, p. 1162) regarding the use of the Zinc Taste Test (ZTT) in patients with anorexia and depression. This test was developed and used because plasma and serum zinc levels were considered unreliable measures of zinc status. Test procedure is given in the Nov 17 letter as well as the finding that patients failing the test may be expected to respond favorably to supplementation with zinc sulfate. Schauss, A., Costin, C., Am J. Nat. Med., Vol. 4, No 10, Dec. 1997. The authors point out that zinc deficiency can directly cause a loss of taste acuity and appetite as was first demonstrated in 1934. Studies have found that gustatory sensitivity (or lack thereof) may be an indicator of the “functional” availability of zinc.
Why Do We Use a Chelated Form of Zinc?
The most efficiently absorbed form of zinc is the chelated form. This is where the zinc is combined with amino acids, which assists in its absorption.
Source: Dr Bruce Bond
Zinc modulates mRNA levels of cytokines.
Bao Bin; Prasad Ananda S; Beck Frances W J; Godmere Michele (Profiled Author: Ananda S Prasad)
American journal of physiology. Endocrinology and metabolism 2003;285(5):E1095-102.
Abstract
Zinc plays an important role in cell-mediated immune function. Altered cellular immune response resulting from zinc deficiency leads to frequent microbial infections, thymic atrophy, decreased natural killer activity, decreased thymic hormone activity, and altered cytokine production. In this study, we examined the effect of zinc deficiency on IL-2 and IFN-gamma in HUT-78 (Th0) and D1.1 (Th1) cell lines and TNF-alpha, IL-1 beta, and IL-8 in the HL-60 (monocyte-macrophage) cell line. The results demonstrate that zinc deficiency decreased the levels of IL-2 and IFN-gamma cytokines and mRNAs in HUT-78 after 6 h of PMA/p-phytohemagglutinin (PHA) stimulation and in D1.1 cells after 6 h of PHA/ionomycin stimulation compared with the zinc-sufficient cells. However, zinc deficiency increased the levels of TNF-alpha, IL-1 beta, and IL-8 cytokines and mRNAs in HL-60 cells after 6 h of PMA stimulation compared with zinc-sufficient cells. Actinomycin D study suggests that the changes in the levels of these cytokine mRNAs were not the result of the stability affected by zinc but might be the result of altered expression of these cytokine genes. These data demonstrate that zinc mediates positively the gene expression of IL-2 and IFN-gamma in the Th1 cell line and negatively TNF-alpha, IL-1 beta, and IL-8 in the monocyte-macrophage cell line. Our study shows that the effect of zinc on gene expression and production of cytokines is cell lineage specific.
Zinc: Mechanisms of Host Defense.
Prasad Ananda S (Profiled Author: Ananda S Prasad)
The Journal of nutrition 2007;137(5):1345-9.
Abstract
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.
Clinical, immunological, anti-inflammatory and antioxidant roles of zinc.
Prasad Ananda S (Profiled Author: Ananda S Prasad)
Experimental gerontology 2008;43(5):370-7.
Abstract
The essentiality of zinc for humans was recognized only 40 years ago. Zinc deficiency was suspected to occur in Iranian patients with growth retardation, hypogonadism in males, hepato-splenomegaly, rough and dry skin, geophagia and severe iron deficiency anemia. Later we documented zinc deficiency in similar patients in Egypt. The diet of these patients consisted of mainly cereal proteins which contained high phytate and this led to decreased availability of iron and zinc. These 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 experimental human model of zinc deficiency, we documented decreased serum testosterone level, oligospermia, severe immune dysfunctions mainly affecting T helper cells, decreased serum thymulin activity hyperammonemia, neuro-sensory disorders and decreased lean body mass. The basic mechanisms of zinc action on immune cells have been reviewed in this paper. Our studies showed that the activation of many zinc dependent enzymes and transcription factors were affected adversely due to zinc deficiency. The gene expression and production of Th1 cytokines were affected adversely due to zinc deficiency. Zinc is also an antioxidant and has anti-inflammatory actions. We have reported decreased plasma zinc, increased plasma oxidative stress markers and increased generation of inflammatory cytokines in the elderly subjects which were corrected by zinc supplementation. In cell culture studies, we have observed that zinc induces A20 which inhibits NF-kappaB activation resulting in decreased generation of inflammatory cytokines.
Zinc Deficiency and Th1 Functions: Molecular Mechanisms
Ananda S Prasad
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
1 August 2002 - 31 January 2007
Abstract
Zinc plays an important role in immune functions in humans. Decreased thymulin activity, decreased production of IL- 2, decreased NK cell lytic activity, decreased cytolytic T cells, anergy, decreased CD4/CD8 and decreased CD4+ CD45RA+/CD4+ CD45RO+ ratios, have been observed in zinc deficient humans and these abnormalities are corrected by zinc supplementation. In order to understand the mechanism of zinc action on IL-2 production, we propose to utilize HUT-78, a ThO human malignant lymphoblastoid cell line for our studies. The human IL-2 gene promoter contains one binding site for genuine Rel/NF-kB factors and binding of NF- kB to DNA is specifically blocked by a zinc chelator and is reconstituted by addition of zinc. NF-kB also binds to the regulatory gene of IL-2 receptor alpha. We hypothesize that in zinc deficient HUT-78 cells, the activation and translocation of NF-kB to nucleus and the gene expression of NF-kB will be decreased and this will lead to decreased gene expression of IL-2 and IL-2 receptor alpha and decreased production of IL-2, sIL-2 receptor alpha and total sIL-2 receptors. The effect of different concentrations of zinc on NF-kB activation in HUT-78 cells will be determined by i) nuclear binding of NF-kB by gel shift assay and confocal imaging ii) gene transfection of cells with luciferase reporter gene vector containing NF-kB enhancer element and iii) assays of phosphorylated, unphosphorylated and ubiquitinated forms of IkB (the inhibitory molecule of the NF-kB complex) in cellular cytosolic fraction. The functional role of NF-kB on transcriptional activation of IL-2 and IL-2 receptor alpha as affected by zinc will be determined by using antisense p105 expression vector in HUT-78 cells. We are also hypothesizing that NF-kB activation, IL-2 production and IL-2 mRNA will be decreased in PHA stimulated zinc deficient human mononuclear cells and that these abnormalities will be corrected by in vivo and in vitro zinc supplementation. For this study we will select appropriate number of healthy ambulatory elderly subjects from a nursing home. Our previous experience indicates that approximately 30 percent of these healthy elderly are zinc deficient.
Zinc deficiency in Mexican American children: influence of zinc and other micronutrients on T cells, cytokines, and antiinflammatory plasma proteins.
Sandstead Harold H; Prasad Ananda S; Penland James G; Beck Frances W J; Kaplan Joseph; Egger Norman G; Alcock Nancy W; Carroll Richard M; Ramanujam V M S; Dayal Hari H; Rocco Carmen D; Plotkin Ruth Ann; Zavaleta Antonio N (Profiled Authors: Ananda S Prasad; Joseph Kaplan)
The American journal of clinical nutrition 2008;88(4):1067-73.
Abstract
BACKGROUND: The Third National Health and Nutrition Examination Survey suggested some Mexican American children are at risk of zinc deficiency. OBJECTIVE: We measured the effects of zinc and micronutrients or of micronutrients alone on indexes of cell-mediated immunity and antiinflammatory plasma proteins. DESIGN: Subjects (n = 54) aged 6-7 y were randomly assigned and treated in double-blind fashion in equal numbers with 20 mg Zn (as sulfate) and micronutrients or with micronutrients alone 5 d/wk for 10 wk. RESULTS: Before treatment the mean +/- SD plasma zinc was 14.9 +/- 1.7 micromol/dL and the range was within the reference; hair zinc was 1.78 +/- 0.52 micromol/g and 41.6% were < or =1.68 micromol/g; serum ferritin was 25.7 +/- 18.6 microg/L and 50.0% were < or =20 microg/L. The zinc and micronutrients treatment increased the lymphocyte ratios of CD4(+) to CD8(+) and of CD4(+)CD45RA(+) to CD4(+)CD45RO(+), increased the ex vivo generation of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), decreased the generation of interleukin-10 (IL-10), and increased plasma interleukin-1 receptor antagonist (sIL-1ra) and soluble tumor necrosis factor receptor 1 (sTNF-R1). Micronutrients alone increased the ratio of CD4(+) to CD8(+) but not of CD4(+)CD45RA(+) to CD4(+)CD45RO(+), increased IFN-gamma but had no effect on IL-2 or IL-10, and increased sIL-1ra but not sTNF-R1. Efficacy of zinc and micronutrients was greater than micronutrients alone for all indexes except the ratio of CD4(+) to CD8(+), which was affected similarly. CONCLUSIONS: Before treatment, concentrations of hair zinc in 41.6%
of subjects and serum ferritin in 50% were consistent with the presence of zinc deficiency. The greater efficacy of the zinc and micronutrients treatment compared with micronutrients alone supports this interpretation.
Zinc enhances the expression of interleukin-2 and interleukin-2 receptors in HUT-78 cells by way of NF-kappaB activation.
Prasad Ananda S; Bao Bin; Beck Frances W J; Sarkar Fazlul H (Profiled Authors: Ananda S Prasad; Fazlul H Sarkar)
The Journal of laboratory and clinical medicine 2002;140(4):272-89.
Abstract
Production of interleukin (IL)-2 is decreased in zinc-deficient human beings, and zinc is essential to IL-2-mediated T-cell activation. We used a human Th(0) malignant lymphoblastoid cell line, HUT-78, to study the effect of zinc on IL-2 production in PHA/PMA activated T-cells. In zinc-deficient cells, the gene expression of IL-2 was decreased by 50% compared with that in zinc-sufficient cells. The effect of zinc was specific and at the transcriptional level. We also showed a significant effect of zinc on the gene expression of IL-2 receptors alpha and beta. Binding of NF-kappaB (a zinc-dependent transcription factor) to DNA was decreased in zinc-deficient cells. Using transfection of expression vectors of anti-sense NF-kappaB p105 (precursor of NF-kappaB p50) in cells, we showed that a decrease in gene expression of IL-2 and IL-2 Ralpha may be partly due to decreased activation of NF-kappaB in zinc-deficient cells. Our studies demonstrate, for the first time, the role of zinc in gene expression of IL-2 and its receptors in HUT-78 cells. We also document that the binding of NF-kappaB to DNA was adversely affected, thereby decreasing the gene expression of IL-2 and IL-2 Ralpha in zinc-deficient HUT-78 cells.
Zinc in Cancer Prevention.
Prasad Ananda S; Beck Frances W J; Snell Diane C; Kucuk Omer (Profiled Author: Ananda S Prasad)
Nutrition and cancer 2009;61(6):879-87.
Abstract
Essentiality of zinc for humans was discovered 45 yr ago. Deficiency of zinc is prevalent world wide in developing countries and may affect nearly 2 billion subjects. The major manifestations of zinc deficiency include growth retardation, hypogonadism in males, cell-mediated immune dysfunctions, and cognitive impairment. Zinc not only improves cell mediated immune functions but also functions as an antioxidant and anti-inflammatory agent. Oxidative stress and chronic inflammation have been implicated in development of many cancers. In patients with head and neck cancer, we have shown that nearly 65% of these patients were zinc deficient based on their cellular zinc concentrations. Natural killer (NK) cell activity and IL-2 generation were also affected adversely. Th2 cytokines were not affected. In our patients, zinc status was a better indicator of tumor burden and stage of disease in comparison to the overall nutritional status. Zinc status also correlated with number of hospital admissions and incidences of infections. NF-kappa B is constitutively activated in many cancer cells, and this results in activation of antiapoptotic genes, VEGF, cyclin DI, EGFR, MMP-9 and inflammatory cytokines. Zinc inhibits NF-kappa B via induction of A-20. Thus, zinc supplementation should have beneficial effects on cancer by decreasing angiogenesis and induction of inflammatory cytokines while increasing apoptosis in cancer cells. Based on the above, we recommend further studies and propose that zinc should be utilized in the management and chemoprevention of cancer.
Don
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