Zinc is an essential trace element for human health and plays a fundamental role in metabolic, immunological and many other biological processes. The effects of zinc are based on the intra- and extracellular regulatory function of the zinc ion (Zn²⁺) and its interactions with proteins. The regulation of cellular zinc homeostasis takes place via a complex network of metal transporters and buffering systems that react to changes in the availability of zinc in nutrition, chronic diseases, infections and many other processes. Zinc deficiency is associated with impairment of numerous metabolic processes, reduced resistance to infections due to impaired immune functions, changes in skin and its appendages and disorders of wound healing and haemostasis. While ischemic heart attacks (myocardial infarction) occur more frequently with meat-based normal diets, haemorrhagic strokes are more frequently observed with vegetarian/vegan diets. The causes are discussed as deficiencies of various micronutrients, such as vitamin B12, vitamin D, various amino acids and also zinc. In the present review, after a description of the functions of zinc and its resorption, a discussion of daily food intake will follow, with a special focus on the importance of food composition and preparation for the zinc balance. The close interrelationships between proteins, especially albumin and zinc will be discussed. Finally, the possible causes and consequences of a zinc deficiency on the blood vessels and blood coagulation are considered.

Decompensated liver cirrhosis has a dismal prognosis, with patients surviving on average for 2–4 years after the first diagnosis of ascites. Albumin is an important tool in the therapy of cirrhotic ascites. By virtue of its oncotic properties, it reduces the risk of cardiovascular dysfunction after paracentesis. Treatment with albumin also counteracts the development of hepatorenal syndrome and spontaneous bacterial peritonitis. More recently, the positive impact of long-term albumin supplementation in liver disease, based on its pleiotropic non-oncotic activities, has been recognized. These include transport of endo- and exogenous substances, anti-inflammatory, antioxidant and immunomodulatory activities, and stabilizing effects on the endothelium. Besides the growing recognition that effective albumin therapy requires adjustment of the plasma level to normal physiological values, the search for substances with adjuvant activities is becoming increasingly important. More than 75% of patients with decompensated liver cirrhosis do not only present with hypoalbuminemia but also with zinc deficiency. There is a close relationship between albumin and the essential trace element zinc. First and foremost, albumin is the main carrier of zinc in plasma, and is hence critical for systemic distribution of zinc. In this review, we discuss important functions of albumin in the context of metabolic, immunological, oxidative, transport, and distribution processes, alongside crucial functions and effects of zinc and their mutual dependencies. In particular, we focus on the major role of chronic inflammatory processes in pathogenesis and progression of liver cirrhosis and how albumin therapy and zinc supplementation may affect these processes.

Chronic hepatitis C (HCV) infection persists in more than 170 million people worldwide and is one of the major causes of hepatic failure and liver transplantation. Current treatment of chronic HCV, consisting of pegylated interferon and ribavirin, is associated with a wide range of side effects, contraindications and costs, and leads to viral clearance in only 50-55% (genotype 1) to 80% (genotype 3) of cases. Thus, the development of more efficient treatment regimes with fewer side effects and costs is of high priority. It is generally accepted that the cellular immune response plays the most important role in determining the outcome of HCV infection. Moreover, oxidative stress is considered to be an important pathogenic factor. Zinc is an essential nutrient for a broad range of biological activities. It is necessary for normal liver function, and vice versa the liver plays a central role in zinc homeostasis. Zinc ions are crucial for multiple aspects of the immune system, including the normal development, differentiation and function of cells belonging to both innate and acquired immunity. Among the immune cells that are affected by zinc deficiency, T lymphocytes are noted to have the highest susceptibility. Zinc deficiency causes substantial impairment of cellular immunity, oxidation and damage to DNA. Several studies have investigated the effect of zinc supplementation in chronic HCV patients. Following zinc supplementation, decreases in the incidence of gastrointestinal disturbances, body weight loss and hair loss were found in patients with chronic HCV, along with improved fingernail health. In addition, zinc administered in combination with IFN-α was more effective against chronic HCV than treatment with IFN-α alone. Finally, in addition to the effects of zinc on immune functions and viral defence, its role as an antioxidant may be important in HCV. To conclude, the controlled application of zinc, particularly in a deficient state, is recommended as a complementary therapy for chronic hepatitis C.

The association between liver cirrhosis and variations of glucose tolerance has been extensively documented and discussed. Zinc is an essential trace element necessary for normal protein metabolism, for the function of more than 200 zinc metalloenzymes, and for a host of physiologic functions. A poor zinc status is common in both liver cirrhosis and diabetes mellitus. Many of the clinical features of liver cirrhosis and diabetes mellitus have been linked to zinc deficiency. Zinc supplementation improved in patients with liver cirrhosis and hepatic encephalopathy with and without diabetes mellitus neurological symptoms and signs of malnutrition. Furthermore, zinc supplementation increased glucose disposal. Summarising these facts, we hypothesise that zinc deficiency is a link between liver cirrhosis and the "liver" diabetes mellitus.

Copper and zinc are essential trace elements which play an important role in various biological processes. Along with various cytokines, glucocorticoids, glucagon and insulin, the acute-phase protein metallothionein is involved in the regulation of immune cell functions. Metallothionein is the central protein regulating zinc concentration. Zinc deficiency is often found in patients with chronic liver disease, chronic kidney disease and diabetes mellitus, and in those with acute infectious diseases. In contrast, copper deficiency is rarely reported. In order to determine whether there is a correlation between zinc and/or copper and selected immunological parameters in patients with chronic liver disease, we investigated plasma levels of zinc and copper, concentrations of interleukin-6 (IL-6) and interferon-γ (IFN-γ), and the enzymatic activity of dipeptidyl peptidase IV (DP IV, CD26) in patients with chronic hepatitis C and in healthy control subjects. Whereas zinc plasma levels did not differ between patients and control subjects, copper concentrations revealed gender-specific differences. The mean copper concentration was higher in female patients with chronic hepatitis C and in female controls compared with the respective male groups. The immunological parameters of IFN-γ concentration and DP IV activity showed similar levels in the patient and control groups. Of note, the mean IL-6 plasma concentrations were significantly elevated in patients with chronic hepatitis C compared with healthy control subjects. In summary, there was no correlation between either zinc or copper concentrations and the immunological parameters measured (IL-6 and IFN-γ levels and DP IV activity) in patients with chronic hepatitis C and in healthy control subjects.

T cell activation mediates immunity to pathogens. On the flipside, T cells are also involved in pathological immune responses during chronic autoimmune diseases. We recently reported that zinc aspartate, a registered drug with high bioavailability, dose-dependently inhibits T cell activation and Th1/Th2/Th17 cytokine production of stimulated human and mouse T cells. To understand the suppressive effect of zinc on T cell function, we here investigated the influence of zinc aspartate on human T cells focusing on the secretion of immunosuppressive cytokines, induction of apoptosis, and caspase 3/7 activity. To this end, we monitored either freshly stimulated or pre-activated human T cells in the presence of zinc aspartate from 40–140 µM over a period of 72 h. Under both experimental conditions, we observed a dose-dependent suppression of human T cell proliferation. While IL-1ra, latent TGF-β1, and IL-10 were dose-dependently reduced, we, unexpectedly, detected elevated levels of IL-16 upon zinc supplementation. In addition, the number of cells with active caspase 3/7 and, consecutively, the amount of cells undergoing apoptosis, steadily increased at zinc aspartate concentrations exceeding 100 µM. Taken together, our findings suggest that zinc aspartate impairs T cell fitness and might be beneficial for the treatment of T cell-mediated autoimmune diseases.