Oral Zinc Therapy Research Articles

Oral zinc therapy for zinc deficiency-related telogen effluvium

Zinc is crucial for maintaining human body homeostasis and is one of the major components of hormones, signal molecules, and enzymes. Zinc deficiency is caused by insufficient uptake of zinc from food, or caused by malabsorption syndromes, increased gastrointestinal and urinary losses, and administration of various medications. In order to test whether oral zinc administration can successfully improve zinc deficiency-related alopecia, we treated five patients with zinc deficiency-related telogen effluvium with oral zinc administration in the form of polaprezinc (Promac®). In all patients, hair loss was cured or improved. The administration of zinc for zinc deficiency-related alopecia may recover appropriate activities of metalloenzymes, hedgehog signaling, and immunomodulation, all of which are required for normal control of hair growth cycle.

Translational Approaches for Pharmacotherapy Development for Acute Diarrhea

Areport is presented of a National Institute of Diabetes and Digestive and Kidney Diseases–sponsored single topic conference designed to determine scientific advances needed to encourage development of pharmacotherapy for diarrheal diseases. Acute diarrheal diseases are a global public health problem in developing and developed countries. They are a leading cause of mortality and morbidity for children under the age of 5 worldwide and have a major economic impact in developed countries. Although oral rehydration solution (ORS) along with oral zinc therapy has reduced mortality owing to acute diarrheal diseases, there are essentially no other approved, safe, and effective drugs to decrease stool volume and prevent fluid loss. On September 25–27, 2011, the National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop on Translational Approaches for Pharmacotherapy Development for Acute Diarrhea to assess current treatments for acute diarrhea, to identify common host pathways targeted by infectious agents associated with acute diarrhea, to evaluate which pathophysiologic mechanisms are most clinically relevant as potential targets, and to identify promising areas for translational research.

Paradigm Shift in Treatment of Alzheimer′s Disease: Zinc Therapy Now a Conscientious Choice for Care of Individual Patients

Breakthrough in treatment of Alzheimer's disease with a shift from irrational dangerous chelation therapy to rational safe evidence based oral zinc therapy. Evidence based medicine: After synthesizing the best available clinical evidence I conclude that oral zinc therapy is a conscientious choice for treatment of free copper toxicosis in individual patients with Alzheimer's disease. Hypothesis 1: Age related free copper toxicosis is a causal factor in pathogenesis of Alzheimer's disease. There are 2 neurodegenerative diseases with abnormalities in copper metabolism: (a) the juvenile form with degeneration in the basal ganglia (Wilson's disease) and (b) the age related form with cortical neurodegeneration (Alzheimer's disease). Initially the hypothesis has been that neurodegeneration was caused by accumulation of copper in the brain but later experiences with treatment of Wilson's disease led to the conviction that free plasma copper is the toxic form of copper: it catalyzes amyloid formation thereby generating oxidative stress, free radicals and degeneration of cortical neurons. Hypothesis 2: Oral zinc therapy is an effective and safe treatment of free copper toxicosis in Alzheimer's disease. Proposed dosage: 50 mg elementary zinc/day. Warning: Chelation therapy is irrational and dangerous in treatment of copper toxicosis in Alzheimer's disease.

Necrolytic acral erythema

Necrolytic acral erythema (NAE) is a recently recognized dermatosis almost exclusively associated with hepatitis C virus (HCV) infection and closely related to a group of necrolytic erythemas and metabolic syndromes. NAE is characterized by pruritic, symmetric, well-demarcated, hyperkeratotic, erythematous-to-violaceous, lichenified plaques with a rim of dusky erythema on the dorsal aspects of the feet and extending to the toes. Based on morphology and histopathologic features, NAE can be difficult to distinguish from certain groups of necrolytic erythemas, which include necrolytic migratory erythema, acrodermatitis enteropathica, biotin deficiency, niacin deficiency, and essential fatty acid deficiencies. The condition is particularly important for clinicians to diagnose because the majority of the patients present to dermatologists without a known history of HCV infection. Thus, NAE can serve as a cutaneous marker for underlying HCV infection. Resolution of NAE can be achieved by treatment of the underlying HCV infection and the use of oral zinc therapy.

Impact of oral zinc therapy on the level of sex hormones in male patients on hemodialysis

Background: Sexual dysfunction in chronic renal failure patients undergoing hemodialysis is common. It is demonstrated that the zinc level is significantly lower in the hemodialysis patients. Objective: In this clinical trial, we investigate the effect of zinc supplement therapy on the serum levels of sexual hormones in hemodialysis male patients. Patients and methods: We carried out a clinical trial study including 100 of our male patients with end-stage renal disease on hemodialysis. Testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and zinc plasma level were measured in all of the patients. The patients received zinc supplement (zinc sulfate, 250 mg/day) for 6 weeks, and sex hormones and zinc plasma level were checked again. Results: Serum level of FSH and prolactin did not have any significant changes before and after intervention, but serum level of testosterone, LH, and zinc increased significantly. Discussion: These results suggest that although zinc administration did not have a definite effect on hemodialysis patients with sexual dysfunction, it can cause increase in the serum level of sex hormones which may improve the sexual function of the patients in some aspects.

Effect of Oral Zinc Therapy on Osteogenesis in Rabbits

Effect of Oral Zinc Therapy on Osteogenesis in Rabbits

Changes in Seminal Quality Following Oral Zinc Therapy

33 subfertile men with idiopathic asthenozoospermia and/or oligozoospermia were treated with oral zinc sulphate. After treatment a significant improvement in the percentage progressive and total sperm motility was noted accompanied by a significant increase in seminal fluid zinc levels.

3 years of continuous oral zinc therapy in 4 patients with Wilson's disease.

A competitive relationship exists between copper and zinc: among other effects, excessive dietary zinc is known to decrease the absorption of copper from the gastro-intestinal tract. The purpose of this study is to investigate the effectiveness of oral zinc therapy in 4 patients with Wilson's disease, who, during a 3-year period, took zinc as their only medication to influence their copper metabolism. Physical examinations, oral 64Cu loading tests, plasma concentrations of copper, zinc and ceruloplasmin, and the urinary copper excretion were used to monitor the effect of therapy. The dosages used ranged from 3 x 100 to 3 x 400 mg zinc sulphate per day. The clinical and biochemical results of the oral zinc therapy were good in all 4 patients and no toxic side-effects were seen. Our conclusion from this study is that oral zinc may well be a low toxic alternative to D-penicillamine in the treatment of Wilson's disease.

A Meta-analysis of the Effects of Oral Zinc in the Treatment of Acute and Persistent Diarrhea

Children in developing countries are at a high risk for zinc deficiency. Supplemental zinc has previously been shown to provide therapeutic benefits in diarrhea. The objective of this study was to examine the efficacy and safety of supplemental oral zinc therapy during recovery from acute or persistent diarrhea. We conducted a meta-analysis of randomized, controlled trials to compare the efficacy and safety of supplementary oral zinc with placebo in children with acute and persistent diarrhea. Results were reported using a pooled relative risk or a weighted mean difference. A total of 22 studies were identified for inclusion: 16 examined acute diarrhea (n = 15,231), and 6 examined persistent diarrhea (n = 2968). Mean duration of acute diarrhea and persistent diarrhea was significantly lower for zinc compared with placebo. Presence of diarrhea between zinc and placebo at day 1 was not significantly different in acute diarrhea or persistent diarrhea trials. At day 3, presence was significantly lower for zinc in persistent diarrhea trials (n = 221) but not in acute diarrhea trials. Vomiting after therapy was significantly higher for zinc in 11 acute diarrhea trials (n = 4438) and 4 persistent diarrhea trials (n = 2969). Those who received zinc gluconate in comparison with zinc sulfate/acetate vomited more frequently. Overall, children who received zinc reported an 18.8% and 12.5% reduction in average stool frequency, 15.0% and 15.5% shortening of diarrhea duration, and a 17.9% and 18.0% probability of reducing diarrhea over placebo in acute and persistent trials, respectively. Zinc supplementation reduces the duration and severity of acute and persistent diarrhea; however, the mechanisms by which zinc exerts its antidiarrheal effect have not been fully elucidated.

Transient zinc deficiency in preterm infants

Zinc is an essential element and necessary for various cellular functions. Preterm infants may have a negative zinc balance and are therefore especially susceptible for symptomatic zinc deficiency. We report on a preterm child with distinct clinical manifestations of zinc deficiency confirmed by histology and laboratory analysis who quickly healed with oral zinc therapy.

Paradigm shift in treatment of Wilson's disease: Zinc therapy now treatment of choice

Zinc therapy has replaced penicillamine as first-line therapy for Wilson's disease. New guidelines reflect the paradigm shift in treatment that has occurred in recent years. In the old paradigm, Wilson's disease was seen as genetic disorder associated with the accumulation of copper in the liver and in other organs once the liver had become overloaded with copper. When left untreated, the disease was regarded as uniformly fatal. The old treatment guidelines advised, ‘decoppering’ with penicillamine because this chelating agent was considered effective in restoring most patients to health. Before the start of treatment, patients were warned that their symptoms could worsen during the first weeks or months of therapy, so as to prevent them from abandoning penicillamine therapy in dismay. In the new paradigm, Wilson's disease is seen as a hereditary disorder associated with copper intoxication. The essence of symptomatic Wilson's disease is poisoning by free copper in the blood, that is, by copper that is not bound to ceruloplasmin. This form of copper is toxic, whereas accumulated copper and copper that is bound to ceruloplasmin or metallothionein is not. The treatment of symptomatic Wilson's disease is no longer aimed at ‘decoppering’, the removal of accumulated copper, but at the normalization of the free copper concentration in blood, to reverse the copper poisoning. This can be achieved safely and effectively with zinc therapy. Zinc induces metallothionein, a highly effective detoxification protein that binds copper. Oral zinc therapy leads to storage of metallothionein-bound copper in the mucosa of the gut and to the excretion of copper via the stools. New treatment guidelines advise against the use of chelating agents as initial treatment because they may aggravate copper intoxication and cause iatrogenic deterioration.

Treatment of Wilson’s disease with zinc from the time of diagnosis in pediatric patients: A single-hospital, 10-year follow-up study

Wilson's disease (WD) is an inherited disorder of copper metabolism characterized by a failure of the liver to excrete copper, leading to its accumulation in the liver, brain, cornea, and kidney, with resulting chronic degenerative changes. It is generally accepted that "presymptomatic" patients--in whom WD is diagnosed in childhood and who are defined as those who, although still asymptomatic, do have liver disease, as indicated by increased serum concentrations of transaminases--should be treated prophylactically. Here we report our results in 22 children treated with continuous oral zinc therapy for 10 years. Zinc sulfate was administered at a dosage of 25 mg elemental zinc twice a day until the age of 6 years, 25 mg three times a day between the ages of 7 and 16 years or until the child attained a body weight of 125 lb, and 50 mg three times a day thereafter. Five years after the start of zinc treatment, we noted highly significant decreases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and urinary copper excretion, but white blood cell counts did not vary significantly. Six of 22 patients continued to demonstrate greater-than-normal ALT concentrations and only 1 patient demonstrated an ALT concentration more than 1.5 times the upper normal limit. Further decreases in ALT, AST, and urinary copper excretion were observed at the end of the 10-year follow-up, but these decreases were not statistically significant. Only 1 patient continued to demonstrate abnormal ALT levels. Again, white blood cells showed no significant variations. All histologic scores (steatosis, inflammation, and fibrosis) were significantly decreased after treatment. Hepatic copper content was also significantly decreased, although it remained higher than normal in all patients. The removal of toxic copper was confirmed by disappearance of Kayser-Fleischer rings in 3 patients. Zinc did not have adverse effects on growth. The efficacy of zinc in WD in presymptomatic pediatric patients has been established in previous studies, and our study adds considerably to the earlier findings because it includes a large number of very young children, as many as 11 younger than 6 years and 20 younger than 10. The excellent clinical results in all patients, coupled with the improvement in hepatic histologic findings in the vast majority, indicate convincingly that zinc treatment can control the disease effectively and safely, preventing its progression over the course of 10 years. Histologic findings reportedly improved in 3 patients treated in an earlier study, but our data are numerically much more relevant. Notably, histologic study of the liver revealed that copper concentration was reduced by treatment, suggesting that oral zinc was able not only to prevent further accumulation of copper but also to promote, at least in part, the depletion of its stores. The lack of adverse effects of zinc on growth suggests that our patients received enough anticopper therapy to prevent damage resulting from copper toxicity but an adequate amount of copper for proper growth and development. In conclusion, our findings indicate that zinc is the treatment of choice in presymptomatic pediatric patients with WD.

Necrolytic Acral Erythema

Recently, necrolytic acral erythema (NAE) has been described as a cutaneous marker for hepatitis C virus (HCV) infection. Only 2 cases have been reported in the United States. Successful remission has been induced only with interferon therapy with or without ribavirin. We describe a 46-year-old, HCV-positive African American woman with well-defined, dusky, erythematous plaques on the dorsa of the feet, Achilles tendons, legs, knees, and elbows. Histologic examination revealed confluent upper epidermal necrosis, acanthosis, papillomatosis, and superficial and deep perivascular inflammation. She was diagnosed as having NAE. We induced successful disease remission with oral zinc administration. This is the third NAE case reported in the United States and the first report of disease remission with oral zinc therapy alone. Since its initial description in Egypt, more cases of NAE are being reported in the United States. Increased awareness of this entity is crucial. Oral zinc might represent a less toxic alternative therapeutic option for patients with NAE.

Oral zinc therapy in patients with supposed mild zinc deficiency--a critical review.

The importance of zinc in many processes of diseases remains unclear up today. Nevertheless many biochemical or clinical studies let support a high clinical relevance of trace elements especially zinc in the therapeutic concepts of diseases. Unfortunately the border between severe (or real) and mild (or subclinical) zinc deficiency is not clear defined. In addition methodical problems in determination of trace elements and misinterpretations of study results lead to unjustified assignment from several diseases in the group of zinc deficiency disorders. Another current problem is the consideration of bioavailability of oral commercial trace element products. Especially the regulation of zinc uptake in human under normal conditions and in case of zinc deficiency is not clear at this time. These problems let become tangled the actual literature for the clinical active physician at the field of zinc. In this mini review there is given an overview about published clinical studies with oral zinc supplementation in the past years.

Acute Hepatitis After Starting Zinc Therapy in a Patient With Presymptomatic Wilson's Disease

HepatologyVolume 32, Issue 4 p. 877-877 CorrespondenceFree Access Acute hepatitis after starting zinc therapy in a patient with presymptomatic Wilson's disease Luis Castilla-Higuero M.D., Ph. D., Luis Castilla-Higuero M.D., Ph. D. Digestive Diseases Unit, Valme University Hospital, Seville, SpainSearch for more papers by this authorManuel Romero-Gomez M.D., Ph. D., Manuel Romero-Gomez M.D., Ph. D. Digestive Diseases Unit, Valme University Hospital, Seville, SpainSearch for more papers by this authorEmilio Suarez M.D., Emilio Suarez M.D. Digestive Diseases Unit, Valme University Hospital, Seville, SpainSearch for more papers by this authorManuel Castro M.D., Ph. D., Manuel Castro M.D., Ph. D. Digestive Diseases Unit, Valme University Hospital, Seville, SpainSearch for more papers by this author Luis Castilla-Higuero M.D., Ph. D., Luis Castilla-Higuero M.D., Ph. D. Digestive Diseases Unit, Valme University Hospital, Seville, SpainSearch for more papers by this authorManuel Romero-Gomez M.D., Ph. D., Manuel Romero-Gomez M.D., Ph. D. Digestive Diseases Unit, Valme University Hospital, Seville, SpainSearch for more papers by this authorEmilio Suarez M.D., Emilio Suarez M.D. Digestive Diseases Unit, Valme University Hospital, Seville, SpainSearch for more papers by this authorManuel Castro M.D., Ph. D., Manuel Castro M.D., Ph. D. Digestive Diseases Unit, Valme University Hospital, Seville, SpainSearch for more papers by this author First published: 30 December 2003 https://doi.org/10.1053/jhep.2000.17917Citations: 12AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat REFERENCES 1 Brewer GJ, Johnson VD, Dick RD, Hedera P, Fink JK, Kluin KF. Treatment of Wilson's disease with zinc. XVII: Treatment during Pregnancy. Hepatology 2000; 31: 364– 370.MEDLINE 2 Brewer GJ, Yuzbasiyan-Gurkan V. Wilson Disease. Medicine 1992; 71: 139– 164.MEDLINE 3 Brewer GJ. Practical recommendations and new therapies for Wilson's disease. Drugs 1995; 50: 240– 249.MEDLINE 4 Lang CJG, Rabas-Kolominsky P, Engelhardt A, Kbras G, Konig HJ. Fatal deterioration of Wilson's disease after institution of oral zinc therapy. Arch Neurol 1993; 50: 1007– 1008.MEDLINE 5 Walshe JM, Munro NAR. Zinc-induced deterioration in Wilson's disease aborted by treatment with penicillamine, dimercaprol, and a novel zero copper diet. Arch Neurol 1995; 52: 10– 11.MEDLINE 6 Mulder TP, Janssens AR, Verpaget HW, van Hattum Lamers CB. Metallothionein concentration in the liver of patients with Wilson's disease, primary biliary cirrhosis, and liver metastasis of colorectal cancer. J Hepatol 1992; 16: 346– 350.MEDLINE 7 Friedman LS. Zinc in the treatment of Wilson's disease: how it works. Gastroenterology 1993; 104: 1566– 1568.MEDLINE Citing Literature Volume32, Issue4October 2000Pages 877-877 ReferencesRelatedInformation

Acrodermatitis enteropathica: Case report analyses of zinc metabolism electron microscopic examination and immune function

Acrodermatitis enteropathica (AE) is a rare autosomal recessive disease that results from an unknown defect in zinc metabolism and usually occurs in the first year of life. Zinc is required for the structure and activity of ∼300 metalloenzymes. Therefore, every system could be affected functionally or structurally by this defect. An 11-year-old girl presented with rashes around mucocutaneous junctions, periorbital and perianal areas, and on the extremities. These clinical signs and symptoms had started when she was 3.5 months old. She was the third child of healthy parents who are second cousins. One of her brothers had died with similar manifestations when he was 3 years old. In the initial physical examination, growth retardation, partial alopecia, squamous skin eruptions around the body orifices, pustular lesions on her knees and hands, dystrophic changes of the finger and toe nails, and taste dysfunction were prominent findings. Laboratory results revealed: haemoglobin: 12.3 gr/dl; WBC: 7,300/mm3; platelet count : 402,000 /mm3; serum iron : 152 μg/dl; total iron binding capacity : 501 μg/dl; transferrin saturation : 25.1 %; serum cu level: 118 μg/dl (123–187 μg/dl); and alkaline phosphatase :18 IU/L (98–279 U/L ). Serum electrolytes, hepatic, and renal function tests were normal. Zinc levels in different body compartments were decreased (plasma Zn: 20 μg/dl; erythrocyte Zn: 5.7μg/ml; hair Zn: 116.6 μg/g) with normal zinc absorption. Zinc 65 absorption and retention test showed initial elevation, but decreased rapidly after the fourth day compared to the controls and her other family members. By electron microscopy, intestinal mucosal biopsy revealed Paneth cell inclusions. Lymphocyte subpopulations and results of neutrophil chemotaxis also showed some abnormalities. Pathological clinical findings and symptoms totally disappeared in a few weeks with oral zinc therapy (ZnSO4, 2 mg/kg/day). J. Trace Elem. Exp. Med. 13:317–325, 2000. © 2000 Wiley-Liss, Inc.

Copper Deficiency Anemia and Prolonged Enteral Feeding

Letters1 September 1994Copper Deficiency Anemia and Prolonged Enteral FeedingJiro Masugi, MD, Masahiko Amano, MD, and Tsuneo Fukuda, MDJiro Masugi, MDSearch for more papers by this author, Masahiko Amano, MDSearch for more papers by this author, and Tsuneo Fukuda, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-5-199409010-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Copper deficiency is a rare disease because of the ubiquitous distribution of copper and low daily requirements. Copper deficiency has been reported in patients who receive total parenteral nutrition [1], who have the short-bowel syndrome [2], and who receive oral zinc therapy [3] and in premature infants [4]. We describe a patient who developed copper deficiency anemia after long-term enteral feeding.A 77-year-old woman was hospitalized in July 1993 because of severe macrocytic anemia. She had an erythrocyte count of 110 × 104/µL, a hemoglobin level of 4.4 g/dL, a hematocrit of 12.8%, and a mean corpuscular ...

Clinical response of alopecia, trichorrhexis nodosa, and dry, scaly skin to zinc supplementation

Two unrelated patients had dry brittle hair, alopecia, trichorrhexis nodosa, dry scaly skin, pigment dyschromia, short stature, and neurosecretory growth hormone deficiency. By means of the zinc tolerance test, patient 1 was shown to have zinc deficiency, whereas no clear zinc deficiency could be demonstrated in patient 2. In both patients, hair and the skin abnormalities responded to oral zinc therapy.

Transient symptomatic zinc deficiency in a full-term breast-fed infant

A full-term 5-month-old breast-fed female infant presented with a 2-month history of diarrhea and a 1 1/2-month history of an acrodermatitis enteropathica-like skin eruption. Her serum zinc level and the maternal milk zinc level were markedly reduced. All symptoms disappeared promptly with oral zinc therapy, after which the patient's serum zinc level returned to normal.

Dangers of Oral Zinc Therapy

Dangers of Oral Zinc Therapy