1. Physiology of Zinc: General Aspects.- 2. An Introduction to the Biochemistry of Zinc.- 3. Intestinal Absorption of Zinc.- 4. Promoters and Antagonists of Zinc Absorption.- 5. Systemic Transport of Zinc.- 6. Systemic Interactions of Zinc.- 7. Biochemistry of Zinc in Cell Division and Tissue Growth.- 8. Zinc in Cell Division and Tissue Growth: Physiological Aspects.- 9. Biochemical Pathologies of Zinc Deficiency.- 10. Zinc and Iron in Free Radical Pathology and Cellular Control.- 11. Zinc Status and Food Intake.- 12. Zinc and Reproduction: Effects of Deficiency on Foetal and Postnatal Development.- 13. A Note on Zinc and Immunocompetence.- 14. Zinc and Behaviour.- 15. Neurobiology of Zinc.- 16. Zinc in Endocrine Function.- 17. Severe Zinc Deficiency.- 18. Mild Zinc Deficiency in Human Subjects.- 19. Putative Therapeutic Roles for Zinc.- 20. The Diagnosis of Zinc Deficiency.- 21. Human Zinc Requirements.- 22. Dietary Pattern and Zinc Supply.- 23. Zinc Excess.- 24. The Biological Significance of Zinc for Man: Problems and Prospects.

Zinc in Human Biology

Zinc is an essential trace element crucial for the function of more than 300 enzymes and it is important for cellular processes like cell division and apoptosis. Hence, the concentration of zinc in the human body is tightly regulated and disturbances of zinc homeostasis have been associated with several diseases including diabetes mellitus, a disease characterized by high blood glucose concentrations as a consequence of decreased secretion or action of insulin. Zinc supplementation of animals and humans has been shown to ameliorate glycemic control in type 1 and 2 diabetes, the two major forms of diabetes mellitus, but the underlying molecular mechanisms have only slowly been elucidated. Zinc seems to exert insulin-like effects by supporting the signal transduction of insulin and by reducing the production of cytokines, which lead to beta-cell death during the inflammatory process in the pancreas in the course of the disease. Furthermore, zinc might play a role in the development of diabetes, since genetic polymorphisms in the gene of zinc transporter 8 and in metallothionein (MT)-encoding genes could be demonstrated to be associated with type 2 diabetes mellitus. The fact that antibodies against this zinc transporter have been detected in type 1 diabetic patients offers new diagnostic possibilities. This article reviews the influence of zinc on the diabetic state including the molecular mechanisms, the role of the zinc transporter 8 and MT for diabetes development and the resulting diagnostic and therapeutic options.

Zinc and diabetes--clinical links and molecular mechanisms.

Objectives
Small intestinal permeability is often increased in patients with Crohn's disease and may be pathogenic for clinical relapses. No effective prophylactic treatment is available for these patients. The aim of this study was to ascertain whether zinc supplementation may improve intestinal permeability.

Methods
We studied 12 patients with quiescent Crohn's disease who had been in remission for at least 3 months and had increased intestinal permeability on two separate occasions within the last 2 months. Patients received oral zinc sulfate supplements (110 mg three times a day) for 8 weeks and were followed-up for 12 months thereafter to monitor relapses.

Results
We found that the lactulose/mannitol ratio was significantly higher before supplementation than after (0.041 ± 0.003 versus 0.026 ± 0.005). During follow-up, 10 patients had normal intestinal permeability and did not relapse; of the remaining two who had increased intestinal permeability, one relapsed.

Conclusions
Our findings show that zinc supplementation can resolve permeability alterations in patients with Crohn's disease in remission. Improving intestinal barrier function may contribute to reduce the risk of relapse in Crohn's disease.

Zinc supplementation tightens “Leaky Gut” in Crohn's disease

A new method has been developed for the study of zinc metabolism in man using the stable isotope 67Zn. The technique involves intravenous infusion of the isotope followed by measurements of the plasma and faecal enrichments over a period of days. A procedure for the analysis of Zn isotopes in plasma and faeces is described which requires the separation of Zn from other elements using the chelator dithizone before analysis by thermal-ionization mass spectrometry. The stable isotope technique has been used in conjunction with a metabolic balance study to obtain measurements of Zn absorption and gastrointestinal secretion in a normal subject. Preliminary measurements of the size of the exchangeable pool of Zn have been made as have estimates of the rates of plasma and whole-body Zn turnover. Following an increase in dietary Zn the body appeared to respond in two ways. The gastrointestinal secretion of Zn increased immediately, but only by a relatively small amount. The absorption of Zn initially increased in proportion to the increase in dietary levels but then decreased within 4 d by an amount sufficient to restore Zn balance.

/pdf/zinc-homeostasis-in-man-studies-using-a-new-stable-isotope-6l12p5jzbl.pdf

Zinc homeostasis in man: studies using a new stable isotope-dilution technique

Use of Alcalase in the production of bioactive peptides: A review.

Zinc deficiency is a potential complication of Crohn's disease and we have searched for evidence of this and assessed the possibility that malabsorption of zinc might be a cause. Serum zinc concentrations in 33 patients suffering from Crohn's disease were significantly lower than in 58 normal control subjects (9 . 18 +/- 2 . 3 mumol compared with 13 . 6 +/- 1 . 73 mumol, P < 0 . 0005). Serum zinc correlated well with serum albumin concentrations and the low serum zinc may simply reflect the low serum albumin. Thus its value as an indicator of zinc deficiency is poor. We studied zinc absorption in seven patients with Crohn's disease and compared it with the results obtained previously in five normal subjects using a new technique involving a short-lived isotope of zinc (69mZn). Plasma appearance curves, constructed after an oral dose of isotope, and disappearance curves, after an intravenous dose, were used in a deconvolution computer programme to calculate zinc absorption. Compared with normal subjects, zinc absorption was considerably impaired in patients with Crohn's disease (range 9--45%, compared with 38--75%). This abnormality is a potential cause of zinc deficiency in patients with Crohn's disease.

https://gut.bmj.com/content/gutjnl/21/5/387.full.pdf

MM Molokhia

Papers

Zinc absorption in Crohn's disease.

A simple method for measuring zinc absorption in man using a short-lived isotope (69mZn).