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Department of Nutrition, University of California at Davis, Davis, CA 95616-8669, USA.
Marginal zinc deficiency and suboptimal zinc status have been recognized in many groups of the population in both less developed and industrialized countries. Although the cause in some cases may be inadequate dietary intake of zinc, inhibitors of zinc absorption are most likely the most common causative factor. Phytate, which is present in staple foods like cereals, corn and rice, has a strong negative effect on zinc absorption from composite meals. Inositol hexaphosphates and pentaphosphates are the phytate forms that exert these negative effects, whereas the lower phosphates have no or little effect on zinc absorption. The removal or reduction of phytate by enzyme (phytase) treatment, precipitation methods, germination, fermentation or plant breeding/genetic engineering markedly improves zinc absorption. Iron can have a negative effect on zinc absorption, if given together in a supplement, whereas no effect is observed when the same amounts are present in a meal as fortificants. Cadmium, which is increasing in the environment, also inhibits zinc absorption. The amount of protein in a meal has a positive effect on zinc absorption, but individual proteins may act differently; e.g., casein has a modest inhibitory effect of zinc absorption compared with other protein sources. Amino acids, such as histidine and methionine, and other low-molecular-weight ions, such as EDTA and organic acids (e.g., citrate), are known to have a positive effect on zinc absorption and have been used for zinc supplements. Knowledge about dietary factors that inhibit zinc absorption and about ways to overcome or remove these factors is essential when designing strategies to improve the zinc nutrition of vulnerable groups.
The total content of zinc in the adult human body averages almost 2 g. This is approximately half the total iron content and 10 to 15 times the total body copper. In the brain, zinc is with iron, the most concentrated metal. The highest levels of zinc are found in the hippocampus in synaptic vesicles, boutons, and mossy fibers. Zinc is also found in large concentrations in the choroid layer of the retina which is an extension of the brain. Zinc plays an important role in axonal and synaptic transmission and is necessary for nucleic acid metabolism and brain tubulin growth and phosphorylation. Lack of zinc has been implicated in impaired DNA, RNA, and protein synthesis during brain development. For these reasons, deficiency of zinc during pregnancy and lactation has been shown to be related to many congenital abnormalities of the nervous system in offspring. Furthermore, in children insufficient levels of zinc have been associated with lowered learning ability, apathy, lethargy, and mental retardation. Hyperactive children may be deficient in zinc and vitamin B-6 and have an excess of lead and copper. Alcoholism, schizophrenia, Wilson's disease, and Pick's disease are brain disorders dynamically related to zinc levels. Zinc has been employed with success to treat Wilson's disease, achrodermatitis enteropathica, and specific types of schizophrenia.
Zinc excretion is high in hyperthyroidism, suggesting that the body is trying to get rid of excess zinc. In hypothyroidism, zinc excretion is low.
It is known that patients with hyperthyroidism have a lower zinc content in their erythrocytes, and that this decrement returns to normal after treatment with anti-thyroid drugs. This study was designed to investigate the alteration of body zinc levels in thyroid disorder. Two groups of out-patients associated with hyperthyroidism or hypothyroidism, and a group of normal healthy controls were collected. Zinc contents in the blood, hair and 24-hour urine samples were determined by a flame atomic absorption spectrometer. The results showed that patients with hyperthyroidism had a lower erythrocyte zinc level and an increased urinary zinc excretion (p < 0.05). The hypothyroidism had a higher hair zinc content and a decrement in urinary zinc excretion (p < 0.05). Body zinc levels, excluding the plasma zinc, held a certain correlation to the plasma thyroid hormones levels. The urinary zinc levels showed a more parallel variation in the thyroid disorders (p < 0.05). This data indicates that the alteration of urinary zinc levels might be a useful index for thyroid disorder evaluation. Body zinc could also play a physiological role in the metabolic regulation(s) of a thyroid disorder.
Red blood cell (RBC) zinc (Zn) concentration was measured by atomic absorption spectrophotometry in 28 healthy volunteers, in 46 patients with hyperthyroidism, and in 6 patients with hypothyroidism. The mean (+/- SD) RBC Zn concentration in euthyroid controls was 11.4 +/- 1.5 mg/L RBC, and the normal range defined as the mean +/- 2 SD was 8.5 to 14.3 mg/L RBC. The mean RBC Zn in patients with hyperthyroidism was decreased to 6.4 +/- 1.6 mg/L RBC, and 43 (93%) had low values. The mean RBC Zn in patients with hypothyroidism was not different from that in the controls. There was a significant negative correlation between the concentrations of RBC Zn and those of both plasma thyroxine (T4; r = -0.73) and plasma 3,5,3'-triiodothyronine (T3; r = -0.70). After the treatment of 17 hyperthyroid patients with antithyroid drugs, both mean plasma T4 and T3 levels became normal within 4 weeks, but the normalization of RBC Zn lagged about 2 months behind them. The RBC Zn levels significantly correlated with both the plasma T4 and T3 levels obtained 0, 4, 8, and 12 weeks prior to the RBC sampling, and the highest correlation was observed between the RBC Zn levels and plasma T4 and T3 levels measured 8 weeks previously. These data suggest that RBC Zn concentration in hyperthyroid patients reflects a patient's mean thyroid hormone level over the preceding several months as glycosylated hemoglobin level does in diabetic patients.
Zinc increases the immune response.
Zinc deficiency causes an increase in brain norepinephrine.
Weanling rats were fed a 20% sprayed egg white, zinc-deficient diet for 9 or 10 days. One group (zinc-deficient) was fed ad libitum and given distilled deionized water; a second group was individually pair-fed to rats in the zinc-deficient group; a third group was fed ad libitum; a fourth group was also fed ad libitum, but was fasted overnight prior to slaughter. The latter three groups were given 25 ppm zinc (as zinc acetate) in the water. The brain was excised and the catecholamines were extracted with 0.1 M perchloric acid separated by reverse phase HPLC and measured electrochemically. There did not appear to be a correlation between food intake and brain catecholamine concentrations in any of the groups examined. Brain norepinephrine concentrations in the zinc-deficient rats, however, were significantly higher than in the pair-fed or ad libitum-fed rats.
The following study shows that zinc absorption increased by B-6 and picolinic acid and decreased by dietary iron.
True daily zinc absorption was determined in rats fed a high iron diet (220 ppm Fe; 16.5 ppm Zn), and adequate iron diet (30 ppm Fe) and a high iron diet with varying levels of pyridoxine-HCl (2-40 ppm). Zinc absorption in rats fed the high iron diet was significantly less than in rats fed the adequate iron diet. Zinc absorption in rats fed the high iron diet supplemented with picolinic acid (200 ppm) was markedly increased and did not differ from that in rats fed the adequate iron diet. True, daily zinc absorption increased as the level of dietary vitamin B-6 was increased. Zinc absorption was the least in rats fed 2 ppm vitamin B-6 and was greatest in rats fed 40 ppm vitamin B-6. The concentration of picolinic acid in the pancreas increased as the level of dietary vitamin B-6 was increased. Zinc absorption was significantly elevated in rats fed the high iron diet that contained either 4 or 10 ppm vitamin B-6 and 200 ppm picolinic acid. The turnover rate of 65Zn was determined in rats fed an adequate iron, marginal zinc diet (8.5 ppm Zn) with varying levels of vitamin B-6. The turnover of 65Zn was greatest in rats fed 2 ppm vitamin B-6 and least in rats fed 40 ppm vitamin B-6 or 2 ppm vitamin B-6 + 200 ppm picolinic acid. The results suggest that high levels of dietary iron inhibit zinc absorption via competition for binding with endogenous picolinic acid. The results provide further evidence to support the hypothesis that picolinic acid facilitates absorption of dietary zinc.
Zincdeficiency was produced experimentally in guinea-pigs fed on a diet containing 1.03 mg Zn/kg over a period of 45 days. Clinical signs exhibited in Zn-deficient (ZnD) animals were depression with abnormal posture, scaly skin lesions on various parts of the body, oedematous swelling on hind limbs and marked alopecia. There was no effect on food intake. Serum studies in ZnD group revealed significant decreases in the concentrations of Zn from 20 days onwards, and tri-iodo-thyronine (T3) and thyroxine (T4) from 30 days onwards. Thyroid glands of ZnD animals were smaller in size and pale or whitish pale in colour. Histopathologically, these glands showed changes of atrophy and degeneration in the follicles. It could be concluded that the depletion in serum T3 and T4 due to Zn deficiency was related to thyroid lesions.
The toxicity of zinc ethylene-bis-dithiocarbamate (zineb), a widely used fungicide, was studied in four 4-week-old Friesian calves with immature rumen function. Calves were first subjected to liver biopsy, and thereafter, 3 of them were orally administered 200 mg of zineb/kg of body weight daily for 80 days, whereas the fourth calf served as control and remained untreated. Clinical, hematologic, and pathologic (including ultrastructural) findings were recorded. The distribution in body fluids and tissues of the parent compound and one of its main metabolites, ethylenethiourea (ETU), also was examined. Treated calves had unthrifty appearance and reduction in weight gain. They also had remarkable impairment of thyroid function, as reflected by reduction in serum concentrations of triiodothyronine and thyroxine and increase in weight of the thyroid gland associated with epithelial vacuolization and foci of hyperplasia. Moderate increase in liver glycogen content and impairment in maturation of germ cells were recorded consistently. Whereas zineb was widely distributed in body tissues, ETU accumulated mainly in the liver and the thyroid gland, although noticeable concentrations also were attained in muscle. Data were consistent with involvement of ETU mainly in the pathogenesis of thyroid gland lesions, and indicate that unweaned calves given zineb develop a clinicopathologic syndrome that does not differ qualitatively from that already described in adult cattle exposed to zineb.
In zinc deficient rats, the production of thyroid hormones decreases, but there is a compensatory increase in deiodination activity (the enzymatic conversion of T4 to T3). Interestingly (if my interpretation of this study is correct) the zinc deficient animals were more resistant to the effect of thiouracil, which is an antithyroid similar to PTU which reduces deiodinase activity.
This may relate to humans in this way: if a person with hyperthyroidism is deficient in zinc, then PTU (or Tapazole) may not work well to reduce the thyroid hormone level. Thus in instances when PTU or Tapazole are not reducing the thyroid hormone levels, zinc deficiency should be suspected.
This may explain my personal experience with PTU, which was that I would be relieved of hyper symptoms within 30-60 minutes. I was supplementing zinc and probably had very high body zinc levels. Other hypers have reported that it has taken weeks to obtain benefit from PTU.
Interactive combinations of altered zinc and thyroid states were studied in rats to assess pathophysiologic effects. Clinical signs of zinc deficiency or thyroid alteration were limited to effects on growth rate. Changes in organ and glandular weights and serum thyrotropin levels reflected changes in serum thyroid hormone concentrations. Significantly (probability less than .001), zinc-deficient rats had enhanced hepatic thyroxine-5'-monodeiodinase activity. In addition, the zinc-deficient state was found to be protective against thiouracil-induced suppression of the microsomal-monooxygenase and thyroxine-5'-monodeiodinase enzyme complex. This protective effect was evident by greater thyroxine-5'-monodeiodinase and reduced nicotinamide-adenine dinucleotide phosphate cytochrome c reductase activities, as well as cytochrome P-450 content, in zinc-deficient/thiouracil-treated animals. Thus, the enzyme complex had increased triiodothyronine-generating capacity in conditions of zinc deficiency, which may be important because of the greater biological reactivity of triiodothyronine. Primary zinc deficiency conditions of the magnitude seen in this study and in this-age rat did not appear to alter serum thyroid hormone levels or organ/glandular function. However, concurrent zinc deficiency and altered thyroid status did change thyroid hormone response and disposition, which may be important to populations at risk because of thyroid dysfunctional states.
In the following study, high doses of the zinc compound Zineb caused an increase in thyroid activity in rats.
The effect of zinc ethylenebisdithiocarbamate (zineb) and manganese ethylenebisdithiocarbamate (maneb) has been studied in a chronic experiment (4.5 months) on albino rat thyroid gland and gonads. A complex of biochemical, morphological (histological, histochemical and electronmicroscopic), radiological, functional and biological methods has been employed. Different groups of rats were subjected to inhalatory poisoning with zineb in concentrations 110, 50, 10 and 2 mg.m-3 and maneb in concentrations 135, 12 and 2 mg.m-3. It was established that both compounds provoke toxic irritative changes in the lung and the trachea, more strongly expressed with maneb. A correlation of the dose and the effect was determined. At a zineb dose 0.1 LD50 and 0.01 LD50 applied twice weekly an increased 131l uptake (rebound phenomenon) was found and signs of increased activity of the thyroid gland. At doses 0.1, 0.02 and 0.01 LD50 both for zineb and maneb and an additional dose 0.002 LD50 for maneb, a decrease in the fertile capacity resulting from the damage of the germinative was determined (atrophic changes in Sertoli cells, deserted tubuli seminiferi because of disturbed maturation of the spermatozoa; small number or lack of differentiated forms of spermatogenesis; suppressed ovopoiesis, increased number of atretic follicles, with the domination of the relative part of the growing follicles) and endocrinoactive structures (destruction to disappearing of Leydig's cells; injured cells of Theca interna, granulosa and interstitium). These data as well as the data for teratogenicity give us grounds to recommend a higher security coefficient in hygiene standardization.
Effects on the tissue mineral concentrations of pigs from sows fed four dietary Zn levels were studied. A male and a female from first- and second-parity litters were killed at 1 and 21 d of age. The dams were fed a corn-soybean meal basal diet supplemented with 0, 50, 500 or 5,000 ppm Zn from 30 kg body weight until completion of the second lactation. Pigs from sows fed 5,000 ppm additional zinc had heavier liver, heart, thyroid and adrenal weights relative to their body weight than did pigs from sows on the other treatments. First- and second-parity pigs from sows on the highest Zn supplementation level had higher Fe stores in the liver, higher Zn concentrations in the liver, kidney and pancrease, and higher Cu levels in the kidney compared with pigs from sows on the other treatments. However, Cu concentrations in the liver, heart, pancreas, esophagus, aorta and testes were reduced in pigs from sows on the 5,000 ppm Zn treatment. In first-parity pigs, Ca in the liver was higher for pigs whose dams received 5,000 ppm Zn compared with pigs from sows on all other treatments, and the Mn level was higher compared with pigs from sows receiving 50 or 500 ppm additional zinc. Pigs at 1 d of age from sows on the 0, 50 or 500 ppm treatment had lower hepatic P and Zn concentrations than pigs from sows on the same treatment at 21 d of age. The reverse was true for pigs whose dams received 5,000 ppm Zn.
The following study shows that an iodine deficiency reduces thyroid hormone levels and induces goiter. However a concurrent marginal zinc deficiency does not increase the effects from an iodine deficiency. This indicates that there are no significant zinc and iodine interactions.
The hypothesis tested was that Zn deficiency aggravates impaired thyroid function as induced by I deficiency. In two separate experiments male rats were fed on diets either deficient in Zn or in I, or deficient in both. An identical, restricted amount of food was given to each rat so that body-weight gain of the experimental groups was comparable. Zn deficiency was evidenced by reduced tibial Zn concentrations. I deficiency was evidenced by goitre, reduced urinary I excretion, reduced plasma thyroxine concentrations and reduced absolute amounts and concentrations of thyroxine in the thyroid. Zn deficiency had no effect on the raised thyroid weight as induced by I deficiency. Zn restriction from 184 mumol Zn/kg diet to 31 mumol Zn/kg diet, but not to 92 mumol Zn/kg diet, significantly lowered plasma thyroxine concentration. There were no interrelated effects of Zn and I deficiencies on thyroid hormone levels. These results indicate that marginal Zn deficiency does not influence thyroid hormone metabolism in I deficiency.
Following is an interesting study comparing the effects of zinc supplementation on thyroid hormone levels in genetically obese mice and normal lean mice. Obese mice normally have lower T4, T3, and deiodinase activity than lean mice. While zinc supplementation reduced blood levels of T4 in both groups, only the obese mice had lowered T4, T3, and deiodinase levels in the liver. Interestingly zinc decreased the liver deiodinase activity in all mice.
This study is in contradiction to my conception and the results of other studies which indicate that zinc increases the deiodinase activity. There may be other uncontrolled factors that affected these results, but it's important to look at all studies to try to understand what's going on.
Zinc can get depleted by high phytates, such as in soy, oats, wheat, or other grains. Rapeseed meal (canola oil is made from rapeseeds) has been shown to reduce thyroid function in experimental animals. The following study shows that zinc supplementation can reverse some of these negative effects from rapeseed.
Three groups of 33 90-day-old female Sprague-Dawley rats were fed, ad libitum, the following diets for 2 weeks before breeding. Diet 1 (D1) contained 20% protein from casein, diet 2 (D2) had the same level of protein from Tower rapeseed (Brassica napus) protein concontrate (RPC) and diet 3 (D3) was the same as D2 with a zinc supplement (70 mg/l) in the drinking water. From each group 6 animals were killed before breeding and 5-9 animals were killed at 1 and 2 weeks of gestation and post-partum. From each rat, blood, thyroids, liver and femur were collected for the determination of zinc, copper, iron, manganese, calcium and magnesium. As a measure of the reproductive performance, body weight, number of pups in the uterus or delivered live or dead, and gestations days before parturition were recorded. The pups were examined for obvious deformities and also analysed for the above mineral elements by atomic absorption spectroscopy. In group D2, levels of zinc in maternal serum, liver, femur and in the pups were significantly lower than the comparable levels in the other two groups. The zinc supplemented RPC-fed group did not show the anorexia experienced by the unsupplemented group and there was neither a significant difference between reproductive performances of groups D1 and D3 nor was there any significant difference between the zinc levels determined. It was concluded that the toxic symptoms caused by RPC feeding was attributable to zinc deficiency probably caused by the high phytate level in the RPC.
In the following study zinc was shown to inhibit the T3 binding to rc-erbA beta proteins, indicating "a possible regulatory role for zinc in modulating the intracellular action of thyroid hormone."
The effects of zinc and other divalent metals on the [125I]T3 binding to rat c-erbA alpha and beta recombinant proteins were assessed. The addition of ZnCl2 caused a reversible and dose-dependent inhibition of [125I]T3 binding to rc-erbA beta proteins with half maximum inhibition occurring at 50-100 microM, but no significant effect on [125I]T3 binding to rc-erbA alpha under the same assay conditions. Scatchard analysis revealed a decrease in [125I]T3 binding capacity to beta protein without marked change in Kd values in presence of zinc. Moreover, significant inhibitions of [125I]T3 binding to both alpha and beta proteins were observed in the presence of 100 microM of either MnCl2, CdCl2 or CuCl2, but not MgCl2. Thus, the selective effect of zinc compared to other divalent metals to inhibit T3 binding to rc-erbA beta, but not alpha, proteins was documented and suggest a possible regulatory role for zinc in modulating the intracellular action of thyroid hormone.
The following study shows that zinc increases the immune response in calves to sheep red blood cells, offering evidence that zinc is an immune system stimulant.
Title Serum IgG and IgM responses to sheep red blood cells (SRBC) in weaned calves fed milk supplemented with Zn and Cu.
The following study investigated the effects of zinc and selenium deficiencies on thyroid hormone metabolism. Both zinc and selenium deficiencies decrease the activity of hepatic type I-5'deiodinase and in this study zinc deficiency caused a bigger decrease than selenium deficiency (but the deficiencies may have been uneven).
There were some interesting differences in the effects on zinc and selenium deficiencies on other thyroid hormone values which may help us to determine deficiencies from thyroid tests. Both zinc and selenium deficiencies decrease T3, but zinc deficiency lowers free thyroxin (fT4) but not T4. Selenium deficiency, on the other hand, lowers T4 but not fT4.
48 weaned male Sprague-Dawley rats with an initial average body weight of 41 g were divided into 4 groups of 12 animals (zinc-deficient; zinc-adequate, pair-fed with zinc-deficient group; selenium-deficient; selenium-adequate) for 40 days. All groups were fed a semisynthetic diet with casein being the source of protein. In the selenium-deficient diet, there was a selenium concentration of 0.038 mg/kg. The other diets were supplemented with Na-selenite in order to adjust the selenium concentration to 0.3 mg/kg. In the zinc-deficient diet, there was a zinc concentration of 4.1 mg/kg. The zinc concentrations in the other diets were adjusted to 45 mg/kg by the addition of zinc-sulfate heptahydrate. Zinc-deficient rats were characterized by a markedly reduced alkaline phosphatase activity in their serum, whilst selenium-deficient rats showed a markedly reduced glutathione peroxidase in serum proving their respective zinc-deficient and selenium-deficient states. Zinc deficiency decreased concentrations of triiodothyronine (T3) and free thyroxine (fT4) in serum by approximately 30% when compared with zinc-adequate controls. The concentration of thyroxine (T4) in serum was not affected by zinc deficiency. Selenium-deficient animals had lower concentrations of T3 and T4 than selenium-adequate animals. The concentration of fT4 in serum was not affected by selenium deficiency. The activity of hepatic type I 5'deiodinase was decreased by 67% by zinc deficiency and by 47% by selenium deficiency compared to adequate controls. The study data show that both zinc and selenium deficiency affect the metabolism of thyroid hormones.
Fish erythrocytes were used to elucidate the effect of zinc ions on the cell antioxidant defence system. It was detected that an increase of the Zn2+ concentration (0.01-1 mM) leads to a marked decrease (p < 0.05) in the catalase and the glutathione peroxidase activities. We observed a loss of 14-39% activity of glutathione peroxidase, and 16-20% diminution for catalase. No significant changes were found in case of the superoxide dismutase. Incubation of red blood cells with zinc brought about a decrease of the erythrocyte thiol group content. Treatment of carp erythrocytes with zinc ions also resulted in enhanced hemolysis and in the induction of significant (p < 0.001) changes in the intracellular glucose level. The increase of glucose concentration in the erythrocytes was correlated with increased concentration of metal in the incubation medium. It was proposed that Zn could affect transport systems across the red blood cells and therefore increased the permeability of the membranes to small molecules (e.g. hexose), and led to hemolysis. Zinc ions could act as a potential cell toxicant, leading to disturbances in functions of the antioxidant defence system and to alterations in the erythrocyte membrane properties.
PURPOSE: To determine the effect of moderate zinc deficiency on antioxidant defenses and measures of oxidative stress in the retina and retinal pigment epithelium (RPE) of Brown Norway Rats. METHODS: Twenty-four rats were housed individually and divided into three groups of 8 rats each. Group 1 was fed ad libitum a semipurified control diet formulated to contain 50 parts per million [ppm] total zinc; group 2 was fed ad libitum an identical diet but containing 5 ppm total zinc; and group 3 was pair-fed the control diet but restricted in amount to that consumed by group 2. Food intake was measured daily and the rats weighed weekly. After 6 weeks, the rats were killed and the following measurements were made: serum zinc, serum alkaline phosphatase, retinal zinc, RPE-choroid zinc, RPE-choroid catalase, liver metallothionein (MT), retinal MT, RPE-choroid MT, retinal catalase, and retinal thiobarbituric reactive substances (TBARS). RESULTS: The following showed statistically significant differences between groups 2 and 3, respectively: serum Zn (1216 micro/l versus 1555 microg/l, P < or = 0.01), serum alkaline phosphatase (3.75 U/mg versus 5.10 U/mg, P < or = 0.05), liver MT (4.3 microg/mg protein versus 16.7 microg/mg, P < or = 0.0001), RPE-choroid MT (1.3 microg/mg protein versus 2.2 microg/mg, P < or = 0.02), retinal MT (0.85 microg/mg protein versus 2.8 microg/mg, P < or = 0.05), and retinal TBARS (6.2 nM/mg protein versus 2.2 nM/mg, P < or = 0.05). CONCLUSIONS: The results show that retinal MT and RPE MT concentrations are very sensitive to intake of dietary zinc. The increase in retinal TBARS in group 2 indicates that moderate zinc deficiency increases oxidative stress to the retina. The results also suggest that MT is protective against lipid peroxidation of retinal membranes.
Histidine is an amino acid involved in protein synthesis. In zinc-deficient rats, histidine incorporation into the protein of skin and muscles is decreased. This may have significance in the effects of zinc deficiency on the health of the skin.
The effects of feeding a diet deficient in zinc (Zn) to male rats on histidine metabolism were studied. Results showed that significantly higher percentages of DL-histidine-carboxyl-14C and L-histidine-2-(ring)-14C were oxidized by Zn-deficient rats. The incorporation of L-histidine-2-(ring)-14C into the proteins of skin, muscle, and kidney were significantly reduced in Zn-deficient rats as compared to Zn-supplemented rats. Conversely, the radioactivity of liver protein of Zn-deficient rats was significantly increased. Zn deficiency increased the activities of liver histidase and urocanase but had no effect on the activity of liver histidine-pyruvate transaminase. The increases of enzymatic activities were not due to food intake and can be prevented upon Zn repletion. The liver of Zn-deficient rats contained normal amount of histidine but a reduced quantity of histamine. The results on urinary excretion indicated that Zn-deficient rats discharged the same amounts of one-methyl and three-methyl histidine as Zn-supplemented pair-fed rats. Overall findings support in principle the concept that Zn deficiency results in disturbances of protein metabolism and also indicate that Zn is an important factor in regulating histidine metabolism through the urocanic acid pathway.
Three experiments were conducted with young chicks to investigate the effect of duodenal coccidiosis caused by Eimeria acervulina infection on Zn toxicity, Zn deficiency and the interrelationship between Zn and Cu. The coccidial infection depressed both rate and efficiency of weight gain. Dietary Zn addition at 2000 mg/kg depressed performance only slightly, but the 4000 mg/kg reduced both gain and gain/feed markedly. The coccidial infection appeared to have an ameliorative effect on Zn toxicity as assessed by performance and by hematological parameters. Excess Zn (2000 and 4000 mg/kg) dramatically increased liver, pancreas and bone Zn levels. The coccidial infection, however, decreased tissue Zn levels. Copper toxicity caused by feeding 500 mg Cu per kilogram diet was exacerbated by E. acervulina infection. A Zn-Cu antagonism was observed in both control and in coccidiosis-infected chicks. Excess dietary Zn decreased tissue Cu deposition, but excess Cu did not affect tissue Zn deposition. Copper partially ameliorated Zn toxicity symptoms. The efficacy of Cu in overcoming the Zn-induced depressed hematological parameters, however, was enhanced slightly by coccidiosis. E. acervulina infection did not affect the chick's Zn requirement. Growth data were more reliable as indicators of the Zn requirement than were blood or bone parameters.
Although consequences of zinc deficiency have been recognized for many years, it is only recently that attention has been directed to the potential consequences of excessive zinc intake. This is a review of the literature on manifestations of toxicity at several levels of zinc intake. Zinc is considered to be relatively nontoxic, particularly if taken orally. However, manifestations of overt toxicity symptoms (nausea, vomiting, epigastric pain, lethargy, and fatigue) will occur with extremely high zinc intakes. At low intakes, but at amounts well in excess of the Recommended Dietary Allowance (RDA) (100-300 mg Zn/d vs an RDA of 15 mg Zn/d), evidence of induced copper deficiency with attendant symptoms of anemia and neutropenia, as well as impaired immune function and adverse effects on the ratio of low-density-lipoprotein to high-density-lipoprotein (LDL/HDL) cholesterol have been reported. Even lower levels of zinc supplementation, closer in amount to the RDA, have been suggested to interfere with the utilization of copper and iron and to adversely affect HDL cholesterol concentrations. Individuals using zinc supplements should be aware of the possible complications attendant to their use.zinc toxicity.doc
Mechanisms of zinc (Zn) toxicity are incompletely understood and data regarding potential endocrine alterations in Zn toxicity are scarce. To examine mechanisms of Zn toxicity, day-old chicks were pair-fed diets containing 5280 ppm (Hz) or 73 ppm (CON) Zn. Impaired postnatal growth, independent of feed consumption, and multiple endocrinopathies were observed following short-term (1-2 weeks) exposure to the high Zn diet. Reduced levels of serum cholesterol, high-density lipoprotein cholesterol, and growth hormone were associated with HZ feeding. Depressed levels of circulating thyroid hormones and histological evidence that follicle area of thyroids from HZ birds was 63% less than CON indicated that impaired growth of HZ birds may be caused, in part, by reduced thyroidal function.zinc toxicity effect on thyroid in chicks.doc
The present study indicates that germanium and selenium disturbs bone metabolism in weanling rats, and that this disturbance is reversed by zinc.zinc prevents toxic effects of germanium and selenium.doc
The tumour-localizing abilities of various kinds of porphyrin derivatives in tumour-bearing hamsters were assessed by nitrogen-pulsed laser spectrofluorometry (N2-PLS). On examination of porphine derivatives (from haemoglobin), it was found that the dimer and acetylated and amidated compounds had a high affinity for tumour tissue; the dimer and hydroxylated compound of phorbine derivatives (from chlorophyll) also showed a high affinity. Furthermore, of the metalloporphines (gallium, zinc and indium complexes), those which contained hydrophilic groups showed a high affinity for tumour tissue; of the metallophorbines (gallium, zinc and indium complexes), those which contained hydrophobic groups showed a high affinity. A correlation was found between the side-chain structure of the porphyrins and metalloporphyrins and their affinity for tumour tissue.gallium and porphyrins.doc
Thus, the selective effect of zinc compared to other divalent metals to inhibit T3 binding to rc-erbA beta, but not alpha, proteins was documented and suggest a possible regulatory role for zinc in modulating the intracellular action of thyroid hormone.zinc regulates intracellular action of thyroid hormone.doc
"Zinc Fingers", Daniela Rhodes and Aaron Klug, Scientific American, February 1993
"They play a key part in regulating the activity of genes in many
species, from yeasts to humans. Ten years ago, no one knew they existed."
In order to translate the genetic information in our DNA into amino acids, proteins, messenger RNA, and RNA, certain molecules are required which can read-out the information stored in specific stretches of our DNA. These very specific DNA-reading "transcription factor" molecules can have anywhere from two to 29 "fingers" which fit, like a sophisticated key into a high-precision lock, into highly specific stretches of our DNA.
Transcription factors are made from long strings of amino acids, which are folded into highly specific shapes with many "fingers" - somewhat like we fold a ribbon into loops (or "fingers") to make a Christmas bow.
Now then, and this is the crucial part of the authors' discovery. The 'glue' which forms the straight ribbon of amino acids into finger-like loops is an atom of zinc, at the base of every "finger".
Comments: The conclusions are stunning, powerful, and far-reaching. If there happens to be a zinc deficiency in the organism, the "fingers" of the transcription factors cannot be formed, and although all the genetic information is there, it cannot be transcribed, and used by the organism - be this a yeast cell, a frog, a mouse, or a human. Consequently, the organism will be defective, and its metabolism and immune functions will be severely compromised.
This is the first discovery that the trace elements - there are undoubtedly others than zinc as well - perform a profoundly vital function right at the genetic base of our existence. Hence, the consequences of a zinc deficiency will be very wide-ranging - from many kinds of birth defects to compromised and abnormal metabolic, endocrine and immune functions. Worse, and because of this, a zinc deficiency in the mother can result in faulty genes in her children, due to the sabotaged transcription of her DNA into her offspring's DNA. These children with faulty genes will then pass on their genetic defects to their subsequent offspring and following generations!zinc fingers.doc
Effects on the tissue mineral concentrations of pigs from sows fed four dietary Zn levels were studied. A male and a female from first- and second-parity litters were killed at 1 and 21 d of age. The dams were fed a corn-soybean meal basal diet supplemented with 0, 50, 500 or 5,000 ppm Zn from 30 kg body weight until completion of the second lactation. Pigs from sows fed 5,000 ppm additional zinc had heavier liver, heart, thyroid and adrenal weights relative to their body weight than did pigs from sows on the other treatments. First- and second-parity pigs from sows on the highest Zn supplementation level had higher Fe stores in the liver, higher Zn concentrations in the liver, kidney and pancrease, and higher Cu levels in the kidney compared with pigs from sows on the other treatments. However, Cu concentrations in the liver, heart, pancreas, esophagus, aorta and testes were reduced in pigs from sows on the 5,000 ppm Zn treatment. In first-parity pigs, Ca in the liver was higher for pigs whose dams received 5,000 ppm Zn compared with pigs from sows on all other treatments, and the Mn level was higher compared with pigs from sows receiving 50 or 500 ppm additional zinc. Pigs at 1 d of age from sows on the 0, 50 or 500 ppm treatment had lower hepatic P and Zn concentrations than pigs from sows on the same treatment at 21 d of age. The reverse was true for pigs whose dams received 5,000 ppm Zn.zinc--effects on different mineral concentrations.doc
Zinc deficiency was produced experimentally in guinea-pigs fed on a diet containing 1.03 mg Zn/kg over a period of 45 days. Clinical signs exhibited in Zn-deficient (ZnD) animals were depression with abnormal posture, scaly skin lesions on various parts of the body, oedematous swelling on hind limbs and marked alopecia. There was no effect on food intake. Serum studies in ZnD group revealed significant decreases in the concentrations of Zn from 20 days onwards, and tri-iodo-thyronine (T3) and thyroxine (T4) from 30 days onwards. Thyroid glands of ZnD animals were smaller in size and pale or whitish pale in colour. Histopathologically, these glands showed changes of atrophy and degeneration in the follicles. It could be concluded that the depletion in serum T3 and T4 due to Zn deficiency was related to thyroid lesions.zinc deficiency effects on thyroid in guinea-pigs.doc
Thanks to progress in zinc research, it is now possible to describe in more detail how zinc ions (Zn++) and nitrogen monoxide (NO), together with glutathione (GSH) and its oxidized form, GSSG, help to regulate immune responses to antigens. NO appears to be able to liberate Zn++ from metallothionein (MT), an intracellular storage molecule for metal ions such as zinc (Zn++) and copper (Cu++). Both Zn++ and Cu++ show a concentration-dependent inactivation of a protease essential for the proliferation of the AIDS virus HIV-1, while zinc can help prevent diabetes complications through its intracellular activation of the enzyme sorbitol dehydrogenase (SDH). A Zn++ deficiency can lead to a premature transition from efficient Th1-dependent cellular antiviral immune functions to Th2-dependent humoral immune functions. Deficiencies of Zn++, NO and/or GSH shift the Th1/Th2 balance towards Th2, as do deficiencies of any of the essential nutrients (ENs) - a group that includes methionine, cysteine, arginine, vitamins A, B, C and E, zinc and selenium (Se) - because these are necessary for the synthesis and maintenance of sufficient amounts of GSH, MT and NO. Via the Th1/Th2 balance, Zn++, NO, MT and GSH collectively determine the progress and outcome of many diseases. Disregulation of the Th1/Th2 balance is responsible for autoimmune disorders such as diabetes mellitus. Under Th2, levels of interleukin-4 (II-4), II-6, II-10, leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) are raised, while levels of II-2, Zn++, NO and other substances are lowered. This makes things easier for viruses like HIV-1 which multiply in Th2 cells but rarely, if ever, in Th1 cells. AIDS viruses (HIVs) enter immune cells with the aid of the CD4 cell surface receptor in combination with a number of co-receptors which include CCR3, CCR5 and CXCR4. Remarkably, the cell surface receptor for LTB4 (BLTR) also seems to act as a co-receptor for CD4, which helps HIVs to infect immune cells. The Th2 cytokine II-4 increases the number of CXCR4 and BLTR co-receptors, as a result of which, under Th2, the HIV strains that infect immune cells are precisely those that are best able to accelerate the AIDS disease process. The II-4 released under Th2 therefore not only promotes the production of more HIVs and the rate at which they infect immune cells, it also stimulates selection for the more virulent strains. Zn++ inhibit LTB4 production and numbers of LTB4 receptors (BLTRs) in a concentration-dependent way. Zn++ help cells to keep their LTB4 'doors' shut against the more virulent strains of HIV. Moreover, a sufficiency of Zn++ and NO prevents a shift of the Th1/Th2 balance towards Th2 and thereby slows the proliferation of HIV, which it also does by inactivating the HIV protease. Research makes it look likely that deficiencies of ENs such as zinc promote the proliferation of Th2 cells at the expense of Th1 cells. Zinc deficiency also promotes cancer. Under the influence of Th1 cells, zinc inhibits the growth of tumours by activating the endogenous tumour-suppressor endostatin, which inhibits angiogenesis. The modern Western diet, with its excess of refined products such as sugar, alcohol and fats, often contains, per calorie, a deficiency of ENs such as zinc, selenium and vitamins A, B, C and E, which results in disturbed immune functions, a shifted Th1/Th2 balance, chronic (viral) infections, obesity, atherosclerosis, autoimmunity, allergies and cancer. In view of this, an optimization of dietary composition would seem to give the best chance of beating (viral) epidemics and common (chronic) diseases at a realistic price.zinc what.doc
We have previously reported in patients with hyperthyroidism that the red blood cell (RBC) zinc (Zn) concentration reflects the mean thyroid hormone concentration over the preceding months. In the present study, the concentration of RBC Zn was measured by a simple and easy method with a Zn-test Wako kit. Within-run and between-run precision were 1.4% and 1.3%, respectively. The relationship between RBC concentration and dilution was linear. The average recovery was 103%. A good correlation (r=0.97) was obtained between this method and atomic absorption spectrophotometry. The mean concentration of RBC Zn in 39 euthyroid controls was 12.6 +/- 1.3 mg/l, ranging from 10.4 to 15.1 mg/l. The RBC Zn concentrations in 38 patients with Graves' disease, in 10 patients with silent thyroiditis and in 3 patients with gestational thyrotoxicosis were 7.3 +/- 1.6 (3.2-9.8), 12.0 +/- 1.6 (9.5-14.2) and 11.8 +/- 1.7 (10.5-13.7) mg/l, respectively. The concentration of RBC Zn was able to differentiate hyperthyroid Graves' disease from transient thyrotoxicosis except in 1 case and was a better index than TSH-binding inhibitory immunoglobulin. These results indicate that measuring RBC Zn with the Zinc-test Wako kit is very useful in differentiating hyperthyroid Graves' disease from transient thyrotoxicosis.zinc levels in RBC and Grave's disease.doc
In this study, experimental hyperthyroidism was established and used to investigate possible alterations in the calcium (Ca), magnesium (Mg), and zinc (Zn) homeostasis by assessing their concentrations in plasma and erythrocytes. In the L-thyroxine-induced hyperthyroidism condition, the experimental animals show a significant decrease in erythrocyte Ca, Mg, and Zn concentrations, and a significant decrease in plasma Mg concentration. Significant positive correlations were found for Mg and Zn both in plasma and in erythrocytes. The results suggest that the homeostasis of Ca, Mg, and Zn is altered during experimental hyperthyroidism.zinc and magnesium levels correlate in hyperT.doc