Low Plasma Zinc Research Articles

DiGeorge's Syndrome and Fetal Alcohol Syndrome

Sir.—Four patients with clinical and laboratory features of DiGeorge's syndrome with a history of maternal alcoholism were described by Ammann et al in the article The DiGeorge and the Fetal Alcohol Syndrome (Journal1982;136:906-908). In the article (p 906), Ammann and colleagues stated, Maternal alcoholism may result in the DiGeorge syndrome either as the single causative factor or in conjunction with other as yet unknown teratogens. They made this statement without a specific explanation. I would like to emphasize an important point that was not taken into consideration in their article, ie, the importance of zinc in human intrauterine development.1 In fact, Gordon et al1referred to a possible association between fetal alcohol syndrome and maternal zinc deficiency. In addition, the zinc status of pregnant alcoholic women was analyzed by Flynn et al.2These investigators demonstrated significantly lower plasma zinc levels in both maternal and

Plasma zinc and copper in primary and secondary immunodeficiency disorders

Plasma copper and zinc concentrations were measured in 58 patients with a laboratory-confirmed primary or secondary immunodeficiency. Patients with severe combined immunodeficiency, collagen vascular disease with depressed cell-mediated immunity, and acquired or congenital acrodermatitis enteropathica had mean plasma zinc concentrations substantially below the lower limit of normal. In contrast, patients with primary humoral and polymorphonuclear leukocyte defects had normal plasma zinc concentrations. Patients with primary polymorphonuclear leukocyte defects had a mean plasma copper concentration substantially above the upper limit of normal. Those subjects with primary humoral immunity defects also had significantly elevated plasma copper concentrations in comparison to controls. Plasma copper concentrations in patients with severe combined immunodeficiency or acrodermatitis enteropathica were normal. Cutis laxa patients had low plasma zinc and copper concentrations. These data demonstrate that zinc and copper homeostasis are altered in come immunodeficiency disorders and may be important factors in host defenses. Since it is known that cellular immunity is impaired by zinc deficiency, patients with primary and secondary immunodeficiency states with appropriately documented mild or severe zinc deficiency should receive zinc supplements.

Effect of Zinc Deficiency and Food Restriction on the Plasma Levels of Prostaglandin Metabolites in Male Rats

The pathological signs of zinc and essential fatty acid deficiencies are highly analogous and aspirin, an inhibitor of prostaglandin synthesis, produces similar pathology when fed at toxic levels. To investigate the possibility that impaired prostaglandin biosynthesis is involved in the etiology of zinc deficiency pathology, the plasma concentrations of three prostaglandin metabolites were determined in zinc-deficient and control rats. Immature male rats were fed a purified diet low in zinc (<1 ppm) for 3 weeks. Ad libitum- and pair-fed controls consumed a similar diet supplemented with 100 ppm zinc. The zinc-deficient rats had low plasma zinc and their plasma concentrations of 13,14-dihydro-15-keto PGF2α and 13,14-dihydro-15-keto PGE2 were significantly higher than those of the pair-fed controls. Plasma 6-keto-PGF1α was not different between the zinc-deficient and pair-fed groups, but was significantly lower in deficient rats than in ad libitum-fed controls. The pair-fed controls had significantly lower plasma concentrations of all three metabolites than did the ad libitum-fed control group. The results suggest no impairment of prostaglandin production in zinc-deficient male rats.

Depressed response of plasma iron and zinc to endotoxin and LEM in STZ-diabetic rat.

Laboratory and epidemiological evidence indicate that the enhanced flux of iron and zinc from the plasma to the storage compartments, such as liver, serves as a protective host response to combat infection. Studies were performed to determine the status of this nonspecific immune response in the diabetic animal, since it is commonly held that the diabetic has an increased incidence and susceptibility to infection. Normal rats and rats previously rendered diabetic by streptozotocin (STZ) were injected with either saline or Escherichia coli endotoxin, and plasma levels of zinc, iron, and copper were monitored 8 hr thereafter. Diabetic rats reduced their plasma zinc and iron levels by 35 and 25%, respectively, in response to endotoxin injection whereas control rats had a 70% decrease in zinc and a 46% depression in iron. Insulin administration to the diabetic rats restored the ability to decrease plasma zinc and iron to the same degree as control rats. Plasma copper did not change in any group. Further investigation suggested that the defect in trace metal response occurred after the secretion of leukocytic endogenous mediator (LEM) in the inflammatory response pathway. It is concluded that STZ-diabetic rats have a diminished ability to decrease plasma zinc and iron in response to endotoxin, and that this defect is due to an ineffective response of target tissues to the effects of leukocytic endogenous mediator. Furthermore, it is postulated that the hyperinsulinemia associated with the stress of infection functions to lower plasma zinc and, possibly, iron, thereby allowing the host to better combat infection.

Pica and mineral status in the mentally retarded

A study population consisting of 66 mentally retarded individuals, 60 with and six without pica, was evaluated for iron status, and for plasma and hair zinc, copper, and magnesium levels within a month of known dietary intake. The parameters were all within the normal range for individuals without pica. In contrast, subjects practicing pica had low plasma zinc and elevated plasma copper values as compared to those without pica. Plasma magnesium was in the low normal range for all individuals in the study population. Among the indicators of iron status measured, Hb, hematocrit, plasma iron, total iron-binding capacity, iron saturation, and plasma ferritin, several values were low (p less than 0.001). Depression in plasma zinc level was related to the type and severity of the pica. In plasma, zinc was positively correlated with iron and negatively correlated with copper. No relationships were found between dietary intakes and plasma levels of these minerals. The data suggest that malabsorption of zinc and iron were associated with some types of pica although the individuals received adequate dietary intake of minerals. Zinc, copper, and magnesium concentrations in hair were within normal ranges. Hair was a less sensitive indicator than plasma of trace element status.

Mild Zinc Deficiency and Undernutrition During the Prenatal and Postnatal Periods in Rats: Effects on Weight, Food Consumption, and Brain Catecholamine Concentrations

Rat dams were fed a 20% sprayed egg white diet, containing 10 ppm zinc, during gestation and lactation (ZD) and compared to zinc-adequate pair-fed (PF) and ad libitum fed (AL) control animals. AL dams consumed more food than the ZD group. Throughout gestation AL dams were heavier than PF and ZD dams. During lactation AL dams were heavier than the ZD dams which in turn were heavier than PF dams. Birth weights of ZD pups were less than the PF and AL pups. Postnatal daily weight gains of ZD pups were less than the PF pups which were less than AL pups. After weaning ZD pups fed commercial rat food gained less weight than PF and AL pups, and weight gain of PF and AL pups was similar. ZD dams had lower plasma zinc than control dams at parturition and at the end of lactation. Femur zinc of ZD, PF and AL dams was similar at parturition. ZD dams had lower femur zinc than PF and AL dams after lactation. Femur and liver zinc of ZD pups was lower than in PF and AL pups at birth. Regional brain catecholamine levels were not measured, but whole brain concentrations of catecholamines were not different among the groups. Thus, while mild zinc deficiency adversely affected growth of pups, effects on brain remain to be identified.zinc deficiency food intake weight change brain catecholamines

The importance of dietary protein in the zinc deficiency of uremia

The pathogenesis of zinc deficiency and its relationship to hypogeusia were studied in three chronic dialysis units in Toronto. The difference between low plasma zinc levels at two of the hospitals compared to the normal levels in the third hospital was significantly related to levels of dietary zinc intake which in turn was due to the levels of dietary protein intake. Thus one cause of zinc deficiency in chronic uremia is dietary protein deprivation. In addition, in the hospital with normal plasma levels there was a small but significant rise in plasma zinc postdialysis in contrast to the other two hospitals where there was no change. Thus slight leaching of zinc from dialysis equipment could help prevent zinc deficiency in such patients. Hypogeusia was more common in zinc-deficient patients.

Plasma zinc in hypertension/toxemia and other reproductive variables in adolescent pregnancy

A study was conducted at Charity Hospital, New Orleans, among 272 adolescent pregnant women to ascertain the relationship of pregnancy outcome to plasma zinc level measured once at the time of enrollment. Regression analyses were performed on zinc status versus parameters concerning success of pregnancy corrected for gestational stage at specimen collection. Analysis of variance was performed on groups according to presence or absence of complications, with analyses of covariance used to analyze dichotomous groups. Low, though widely variable, plasma zinc levels were found (mean = 58 +/- 12.6 micrograms/dl). Zinc values differed significantly by gestational stage at collection, the regression coefficient indicating a decline of 0.07 micrograms/dl/day. Plasma zinc level correlated significantly with Hb, red blood cells, ferritin, and folic acid. As to course of pregnancy, women experiencing hypertension/toxemia were found to have significantly lower plasma zinc level. Among infants displaying congenital defects at birth those with undescended testes and metatarsus varus were delivered by mothers whose plasma zinc was well below the mean for the group. These findings indicate the need to investigate the influence of dietary patterns and zinc intake on maternal plasma zinc level and pregnancy outcome, further delineating the role of zinc in human reproduction, particularly hypertension of pregnancy.

Effect of zinc supplementation on the dietary intake, rate of weight gain, and energy cost of tissue deposition in children recovering from severe malnutrition

Children recovering from severe malnutrition on a milk based diet have low plasma zinc concentrations: children recovering on a soya based diet have much lower plasma zinc concentrations, lower rates of weight gain, and higher energy costs of tissue deposition. However, they do not demonstrate the clinical features of anorexia, diarrhea, and skin lesions usually associated with zinc deficiency. We therefore supplemented 16 children with zinc acetate on the basis that a therapeutic response to zinc constitutes the best evidence of a preexisting zinc deficiency. Fourteen of the 16 children had an immediate and definite increase in their rate of weight gain with zinc supplementation. This was associated with a decrease in the energy cost of tissue deposition, regrowth of the thymus, and activation of the sodium pump. We conclude that the children were indeed zinc deficient. We suggest that the anorexia of zinc deficiency is related to an inability to metabolize nitrogen in the zinc deficient state, and that our children did not show an appetitive response because of the relatively low protein content of the diets we used. Based on the premise that the abnormalities seen in our children may have been secondary to mild zinc deficiency, we suggest that limitation of lean tissue synthesis, with resultant obesity, and a propensity to infection are the major features of a mild zinc deficiency. Children undergoing a period of "catch up" weight gain or growth should have supplemental zinc, particularly if they have had diarrhea or if the use of a soya based formula is contemplated.

The vitamin A-zinc connection: a review.

A general summary of typical results involving animal studies is shown in TABLE 7. A consistent and established finding is a reduction of plasma vitamin A concentration in zinc-deficient animals despite diets adequate in vitamin A. However, it appears that the depressed plasma vitamin A is not a result of zinc deficiency per se but rather is nonspecific, resulting from food- and growth-restriction factors associated with zinc deficiency. Food restriction apparently is the critical factor, since both immature and mature nongrowing zinc-deficient animals have exhibited the decreased plasma vitamin A concentration. However, this point needs clarification. Liver vitamin A concentration is usually unaltered by the zinc deficiency, suggesting no defect in absorption or transport to the liver. In regard to retinol-binding protein, it appears from the animal studies that zinc deficiency per se has an effect on both the plasma and liver RBP concentrations. We have hypothesized that zinc deficiency impairs RBP synthesis. It is speculated that only severe zinc deficiency results in a deficit of a sufficient magnitude for impairment of vitamin A metabolism at the cellular level. For example, retinene reductase, an apparent zinc-metallo alcohol dehydrogenase of the retina, appears to be sensitive to a severe zinc deficiency in animal studies. In humans, impaired dark adaptation may be a result of inadequate supplies of the metabolizable zinc necessary to maintain the activity of the enzyme system. Thus, the conversion (dehydrogenation) of vitamin A alcohol to vitamin A aldehyde is impaired, with a resulting abnormality in dark adaptation, i.e., night blindness. Indeed, the limited number of human studies suggest that zinc supplementation may be beneficial to vitamin A metabolism only in conditions where zinc deficiency is prevalent as indicated by low (less than 70 micrograms/100 ml) plasma zinc. Conversely, zinc supplementation is of little benefit in conditions where vitamin A metabolism is altered but zinc status is normal. Therefore, definitive clinical studies involving primary zinc deficiency must be conducted before final conclusions can be made regarding the interrelationships of zinc and vitamin A in health and disease.

Acrodermatitis Enteropathica: Zinc Levels and Cell-Mediated Immunity

Acrodermatitis enteropathica (AE) is a rare vesicobullous skin disorder.1 Genealogic data suggest an autosomal recessive mode of inheritance. The onset of symptoms is generally insidious. In breastfed infants, the disorder may be precipitated on weaning to cow's milk. The frequent occurrence of secondary infections, particularly with opportunistic fungi and bacteria, led to the suspicion that AE is associated with immunodeficiency. "Dysgammaglobulinemia" has been reported in one infant2 and defective chemotaxis in another three patients.3 Limited autopsy observations showed atrophic thymus, tonsils, germinal centers, and Peyer patches.2,4 We report variable impairment of cell-mediated immunity in ten patients with AE of whom eight had low plasma zinc levels.

Plasma zinc and its relationship to clinical symptoms and drug treatment in rheumatoid arthritis.

Total plasma zinc levels in patients with rheumatoid arthritis on different therapeutic treatments were determined in conjunction with total serum proteins, serum albumin and globulin, and articular index of joint tenderness, erythrocyte sedimentation rate, rheumatoid factor, serum copper, and serum iron. There were significantly lower zinc levels in patients with rheumatoid arthritis on nonsteroidal anti-inflammatory drugs than in patients on levamisole and penicillamine. Zinc levels correlated positively with serum albumin, and there was an inverse correlation between zinc levels and both ESR and globulin concentration in all rheumatoid patients. However, the correlation coefficient varied in the different treatment groups. The results of this study support the hypothesis that low plasma zinc level in rheumatoid arthritis is one of the nonspecific features of inflammation.

Plasma zinc concentration in palmoplantar pustulosis.

In 18 ambulant patients with palmoplantar pustulosis low plasma zinc concentrations were observed. During treatment with an all-trans aromatic retinoid (RO-10-9359) the values increased while at the same time the skin condition improved in particular with regard to the pustule formation. The observed low plasma zinc values may in some way be related to pustulosis but not as causal factor.

Plasma zinc and the clinical features of malnutrition

Human protein-energy malnutrition and zinc deficiency have common clinical features. These were related to the plasma zinc concentrations in 42 severely malnourished children. A low plasma zinc concentration was strongly associated with nutritional edema but not with the degree of edema or the plasma albumin concentration. In the absence of edema, there were significant relationships between plasma zinc concentrations and stunting, skin ulceration, and wasting. Infection was not necessarily associated with a lower zinc concentration. From these data, it can be predicted that a malnourished child with edema, skin ulceration, stunting, or severe wasting, will have a low plasma zinc concentration.

Maternal and fetal plasma zinc in pre-eclampsia

Zinc is important for fetal growth and is involved in several important enzyme systems. Maternal and umbilical plasma zinc concentrations were determined in 52 parturient women with mild and severe pre-eclampsia, and were compared with those obtained from 20 women in labor whose pregnancies had progressed normally. A decrease in maternal as well as umbilical plasma zinc concentrations was observed in pre-eclamptic women, and this decrease was statistically significant in severe pre-eclampsia. The causes of these changes in plasma zinc concentrations in pre-eclampsia were discussed, and the possible adverse effects of zinc deficiency on the mother and fetus were mentioned. Low plasma zinc concentrations in pre-eclampsia may be a sign of zinc deficiency, implying possible risks to the mother and her fetus. It is recommended that maintenance of adequate dietary zinc nutrition during pregnancy, and particularly in pre-eclampsia, is important.

Studies of plasma zinc, copper, caeruloplasmin, and growth hormone: With special reference to carcinoma of the bronchus

The levels of plasma zinc, copper, caeruloplasmin, and growth hormone were determined in a group of normal people and in four groups of patients who were suffering from carcinoma of the bronchus, other forms of malignancy, chest illnesses, and diseases other than chest illness or malignancy. The plasma zinc was higher, and the plasma copper lower, in people without malignancy below the age of 30 years than they were in other age groups.It was confirmed that about 66% of patients with carcinoma of the bronchus had plasma zinc levels less than 11.5 mumol/l but low levels were also found in 23% of other cases of malignancy and in 9% of the other patients. In carcinoma of the bronchus the low plasma zinc was found to be associated with epidermoid and anaplastic tumours and was to some extent related to the duration of the disease. In carcinoma of the bronchus the plasma copper was found to be higher than in all other groups, and values higher than 26.5 mumol/l were considered to support a diagnosis of carcinoma of the bronchus. There was, however, no relationship between the increase in the plasma copper and the decrease in the plasma zinc.Raised caeruloplasmin levels above 420 mg/l were found in 65% of cases of carcinoma of the bronchus, and these high levels were usually associated with raised plasma copper. Growth hormone was normal in all groups except six patients with carcinoma of the bronchus with secondary carcinoma of the liver, in whom it was raised. Surgical operations lowered plasma zinc and raised growth hormone but did not affect plasma copper.A plasma zinc below 11.5 mumol/l is helpful in the diagnosis of carcinoma of the bronchus, but by itself it is not sufficiently specific to be considered diagnostic or to form a reliable screening test. A raised plasma copper and a raised plasma caeruloplasmin were useful supportive findings.

Seminal zinc and male infertility

Low seminal plasma zinc is an indication of prostatic secretory dysfunction. We have identified a group of patients referred for infertility evaluation who demonstrated low seminal plasma zinc and decreased sperm motility, in the absence of infection. Treatment of these patients with oral zinc sulfate results in improved sperm motility.

Zinc and the sodium pump in uremia

A defect in sodium transport is known to exist in the leucocytes of uremic patients. Recent work has shown changes in cation flux rates associated with alterations of extracellular zinc concentration. As plasma zinc is known to be low in uremia, the possibility that this might be the cause of the defect in membrane transport was investigated. Plasma zinc was shown to be lower in uremic patients than in normal controls but this was not matched by alterations in leucocyte zinc content. Leucocytes from normal subjects and from patients with uremia have similar increases in the sodium efflux rate constant when exposed to elevated extracellular zinc concentrations. However, the abnormality in leucocyte sodium transport in uremia was not completely corrected by elevation of the extracellular zinc, when compared with normal cells in the same zinc concentrations. Although extracellular zinc is a factor that must be controlled in studies of cellular membrane transport, a low plasma zinc is not the explanation for the defect of sodium transport seen in uremia.

Zinc nutrition and growth in a childhood population

Plasma zinc concentrations are a useful indicator of the zinc nutritional status in humans. This study was designed to evaluate plasma zinc levels in a population stressed by a low-income diet and rapid growth. Plasma zinc concentrations of an inner city childhood population are analyzed by polynominal regression analysis. The resultant age-related plasma zinc curves for male and female subjects are markedly different. Concentrations are lowest during the years of rapid growth, infancy and puberty. The growth velocities (growth indices) of these two populations are calculated and mirror the variation of plasma zinc concentrations. The data suggest that lowered plasma zinc concentrations result from inadequate zinc nutrition during periods of rapid growth.

Effects of copper and zinc status of rats on erythrocyte stability and superoxide dismutase activity.

SummaryErythrocytes from copper deficient rats, which had normal plasma zinc but low plasma copper (high Zn:Cu), were more stable to osmotic stress than those from controls. Erythrocytes from zinc deficient rats, which had low plasma zinc and high plasma copper (low Zn:Cu), were more fragile than those from controls. Addition of Cu2+ and Zn2+ to normal red cells in vitro to provide a low Zn:Cu ratio increased hemolysis and peroxidation. In general erythrocyte membranes are sensitive to the concentrations of extracellular Cu and Zn. The effects are inversely related, zinc exerting a stabilizing and copper a labilizing effect. Ceruloplasmin levels increased in zinc deficiency but RBC superoxide dismutase activity was unaffected. SOD activity is suggested as a clinical index of tissue copper status.