Zinc. Its Importance for Human Health

Zinc (Zn) is an essential micronutrient for humans and is extensively involved in protein, lipid, nucleic acid metabolism, and gene transcription. Its role within the human body is extensive in reproduction, immune function, and wound repair. At the microcellular level, it has a significant effect on the normal functioning of macrophages, neutrophils, natural killer cells, and complement activity. Despite being one of the most abundant trace elements in the human body, zinc cannot be stored in significant amounts and hence requires regular intake or supplementation.

Zinc is the second most abundant trace element (after iron) essential for all living organisms. Zinc exists as a divalent cation (Zn2) and is not redox active under physiological conditions, which explains why zinc performs multifarious physiological roles in a variety of biological processes. Unlike iron and copper, zinc is redox neutral and is reactive as a Lewis acid in biological reactions. Because of these features, zinc plays key roles as a structural, catalytic, and signaling component.

Within proteins, zinc can be coordinated by nitrogen, oxygen, and sulfur atoms and can have different coordination numbers. The zinc proteome estimates that 9% of proteins are zinc proteins in eukaryotes with the number substantially greater in higher organisms. The number of zinc proteins encoded by humans is 10%.

In addition to the roles of zinc described above, zinc is functional as a signaling mediator, leading to the concept that zinc is the “the calcium of the 21st century”. The signaling functions of zinc occur by increases in zinc (Zn2) concentrations triggered by stimuli. Extracellular release of zinc acts as a signaling mediator in endocrine, paracrine, and autocrine systems. In the central nervous system, zinc, which is released from presynaptic neurons upon excitation into synaptic clefts, modulates synaptic transmission by binding to various transporters and receptor channels on postsynaptic neurons. Zinc, co-released from pancreatic -cells along with insulin by glucose stimuli, can suppress hepatic insulin clearance and reduce insulin secretion from the beta-cells.

Zinc homeostasis in the body

The adult human body contains 2–3 g of zinc. Approximately 60% of zinc is stored in skeletal muscle, 30% in bone, 5% in the liver and skin, and the remaining 2–3% in other tissues. Serum zinc accounts for only 0.1% of the body’s zinc, 80% of which is loosely bound to albumin, and 20% of that is tightly bound to beta2-macroglobulin. In the body, 0.1% of the body's zinc is replenished daily through diet. The absorption of zinc in the duodenum and jejunum is strictly regulated; it increases up to 90% when dietary zinc is limited, whereas zinc release, when in excess, is facilitated by the gastrointestinal secretion, sloughing mucosal cells and integument, and renal excretion. Humans appear to have the capacity to regulate whole-body zinc content over a 10-fold change in intake.

Cellular zinc distribution

In cells, zinc is distributed in the cytoplasm (50%), nucleus (30 – 40%), and membrane (10%). Zinc is, however, bound with a myriad of proteins and sequestered into organelles and vesicles, and thus the cytosolic labile (“free”) zinc ion concentration is very low.

Zinc deficiency states

Zinc deficiency can result from inadequate dietary intake, malabsorption, increased body losses, intravenous feeding, or a combination of several of these predisposing factors.

Inadequate dietary intake
- Protein-calorie deficiency
- Vegetarianism
- Patients on protein-restricted diets
- Synthetic diets
Malabsorption
- Acrodermatitis enteropathica
- Coeliac disease and other enteropathies
- Pancreatic insufficiency
- Chronic inflammatory bowel disease
- Immaturity of absorptive systems
Increased body losses
- Starvation
- Burns
- Diabetes mellitus
- Ketoacidosis
- Diuretic treatment
- Proteinuria
- Hepatic disease
- Intravascular hemolysis (for example, sickle cell anemia)
- Porphyria
- Chelating agent therapy
- Chronic blood loss
- Parasitic infection
- Dialysis
- Exfoliative dermatitis
- Excessive sweating
Intravenous feeding

Zinc deficiency is the most significant pathological state involving metal metabolism abnormalities in the body. The risk of zinc deficiency affects approximately 50% of the world’s population. This state in humans occurs in populations whose diets contain a powerful chelator, high phytate concentration (cereal-based diets), and low protein because these factors result in the binding of biogenic zinc. Zinc deficiency in developing countries affects nearly two billion people, mainly because of the high level of phytate in their diet (beans and bread), which impairs the absorption of this element. The minimum zinc requirements in humans corresponding to health, acceptable growth, and well-being change with climate conditions, the existence of stress imposed by trauma, the type of diet consumed, and parasitic infestations and infections.

Clinical manifestations of zinc deficiency

Due to the multitude of basic biochemical functions of zinc in the cells of the human body, there is a broad range of physiological signs of zinc deficiency. These signs vary depending on the severity of the condition. Organ systems known to be affected clinically by zinc deficiency states include the epidermal, gastrointestinal, central nervous, immune, skeletal, and reproductive systems.

Anorexia
Impaired taste and smell
Pica
Growth retardation
Hypogonadism
Impotence
Depression, mood lability, impaired concentration
Intention tremor
Nystagmus
Dysarthria
Photophobia, night blindness, blepharitis
Skin lesions (digits, perineum, parietal, nasolabial folds)
Paronychiae with monilial superinfection
Nails (growth arrest, loss, Beau's lines)
Hair growth arrest or alopecia
Delayed wound healing
Diarrhea
Wilson’s disease
Alzheimer’s disease
Diabetes mellitus
Cardiovascular diseases (atherosclerosis, heart failure)
Renal diseases

Sources of zinc

The richest food sources of zinc include meat, fish, and seafood. Oysters contain more zinc per serving than any other food, but beef contributes 20% of zinc intake from food in western countries because it is commonly consumed. Eggs and dairy products also contain zinc. Beans, nuts, and whole grains contain zinc, but the bioavailability of zinc from these foods is lower than that from animal foods because these foods contain phytates. Phytates, the storage form of phosphorus in plants, bind some minerals such as zinc in the intestine and form an insoluble complex that inhibits zinc absorption. Fruits and vegetables contain very little zinc.

The amount of zinc absorbed from food ranges from 5% to more than 50%, depending on the amount of plant-based foods (and thus phytate) in the diet. The absorption of zinc from mixed meals or diets containing a combination of animal-based and plant-based foods is lower than from diets or meals containing animal-based foods only.

Treatment

Zinc supplementation has been observed to decrease the risk of infection in various studies. In a study conducted on children over 6 months old who were at risk of zinc deficiency, it was observed that zinc supplementation helped in reducing the duration of diarrhea.

Treatment begins with oral replacement. In adults, 2 to 3 mg/kg per day or 20-40 mg daily dose often cures all clinical manifestations within 1 to 2 weeks.

Recommended daily elemental intake is:

3 mg/day for children less than 4 years
5 mg/day for children between 4 and 8 years
8 mg/day for children between 9 and 13 years
9 mg/day for women (non-pregnant and non-lactating)
11 mg/day for men
11 to 12 mg/day in pregnant and lactating women

Individual requirements for zinc, however, depend upon many factors such as stress, medications, illness, and the type of diet a person is consuming (vegetarians have increased zinc requirements). In patients with severe deficiency because of malnutrition or malabsorption in disorders such as Crohn's disease or short bowel syndrome, higher doses of zinc (more than 50 mg/day) may be acutely needed.

When zinc is given for extended periods of time, particularly at high doses, it is important to monitor the levels of copper in the blood.

Formulations of zinc supplements include:

Zinc sulfate
Zinc acetate
Zinc aspartate
Zinc orotate
Zinc gluconate

Patients should be monitored for response to therapy and serum zinc levels should be checked often after supplementation. If there is an inadequate response, the zinc dose may be increased; however, close monitoring for toxicity should be done on higher doses.

At Diagnostiki Athinon we measure Zinc in various biological materials alone or together with other Trace Elements and Heavy Metals.