Zinc

In its inorganic state, zinc is an easily melted, blue-white, shiny metal, but in the human body it takes on completely different forms. Although only a small amount of it is found there, estimated at only two to three grams (which is why we speak of trace elements), its importance is quite fundamental. It is found in virtually all organs and tissues of the body and is bound to more than 2000 different proteins found in the body, together forming so-called metalloproteins (compounds of protein and metal).

A large part of zinc-containing metalloproteins are enzymes – substances without which no biochemical reaction would take place in the body. And some of them are even enzymes that are necessary for the course of epigenetic reactions – that is, those that regulate the activity of individual genes in our DNA. A lack of zinc in the body can therefore be linked to the development of a number of health problems, including some of the most serious. (2, 3)

History

Zinc in its inorganic, metallic form has been known for a very long time. Brass, an alloy of zinc and copper, was demonstrably used in ancient Egypt around 1400 BC, where it was obtained by smelting copper together with zinc ore. However, pure zinc was not isolated until much later, probably in 13th century India.

The zinc content of living tissue was first detected in plants in 1869 and in animals in 1934. Its importance for humans was first discovered in 1961, when the literature described the case of a 21-year-old Iranian farmer who subsisted exclusively on bread cakes, potatoes and milk and suffered from short stature, underdeveloped reproductive organs and anaemia. Shortly thereafter, the case of Egyptian adolescents who subsisted mainly on bread and beans and suffered similar symptoms was described, and when given a diet rich in animal protein and zinc, both their anaemia and the development of their sexual organs improved (6).

Occurrence and absorption of zinc

In the diet, zinc is much more abundant in foods of animal origin. Oysters are the richest source of zinc, but other seafood, especially crabs and lobsters, also contain high amounts. Meat also contains a lot of zinc – more in beef and pork, slightly less in chicken. Dairy products are also a good source, while eggs and fish contain relatively little zinc. Among plant sources, nuts and legumes such as beans, chickpeas, pumpkin seeds and cashew nuts are particularly useful, but the zinc content is generally lower than in animal foods (6, 14, 15).

Dietary zinc is released in the digestive system as ions, which are absorbed in the small intestine. On average, 33 % of the zinc consumed from a normal solid diet is absorbed into the blood, but if the element is supplied in liquid form on an overnight basis, its absorption increases to over 60 %. Zinc is more readily absorbed from a diet high in zinc. In the body, most of the zinc (about 70 %) circulates in the blood bound to the protein albumin, from which it is released into individual tissues as needed (6).

However, the bioavailability of zinc can be significantly impaired by phytic acid, which is found in many seeds, including cereals and legumes. This binds to zinc in the digestive tract and limits its absorption. However, the phytic acid content of the diet can be reduced by certain types of treatment – soaking, sprouting and fermentation are the most effective, as these processes activate enzymes in the grains that break down phytic acid. Milling of the grains also reduces the content of this substance, while heat treatment results in minimal losses. (7-9) Some studies suggest that zinc absorption may also be affected by high dietary calcium content. Although calcium itself has no effect, it may increase the negative effect of phytic acid. However, some studies have not confirmed this (6).

Dietary supplements are generally well absorbed, but there is also great variation. In general, for all minerals, the organically bound ones are better absorbed, while the inorganically bound ones are less well absorbed. In the case of zinc, the absorption and availability was found as follows (in descending order from the best absorbed): bisglycinate (chelate form) – picolinate – oxide – gluconate. (10) Other possible forms are citrullinate and acetate.

However, even people who have sufficient zinc in their diet can suffer from zinc deficiency. The absorption of zinc can be impaired by certain diseases and disorders, typical examples being inflammatory bowel diseases (such as Crohn’s disease or ulcerative colitis) and malabsorption syndromes. Problems can also occur with any ongoing infection and also with acute diarrhoea, as the natural loss of zinc through faeces is increased. Diabetics, people with chronic liver and kidney disease, excessive alcohol consumption (alcohol increases zinc loss in the urine), pregnant and lactating women, and vegetarians and vegans are also at risk of zinc deficiency (6, 12-13).

Zinc is mainly excreted from the body in urine and faeces.

Effect on health

As we have already mentioned, zinc is essential in the body mainly because it is part of a number of key enzymes in the body. And these include those that influence the course of so-called epigenetic reactions.

The fact that a gene is in the DNA of our cells does not mean anything in principle. To be functional, i.e. to be able to make proteins, it must be switched on. Some genes in DNA are permanently switched on or off, others are switched on and off as needed by several biochemical reactions. These include, in particular, DNA methylation, so-called histone modifications affecting the proteins forming the spatial structure of DNA (in particular acetylation, methylation and ubiquination of histones) and, of course, the reactions opposite to them, i.e. demethylation, deacetylation, deubiquination…).

Zinc is a component of most of the enzymes that are necessary for these reactions. Therefore, if there is a deficiency of zinc in the body, it can seriously interfere with the function of a number of important genes in the body, which can result in an increased risk of a number of diseases and problems (4, 16).

The following lines list the problems in which zinc deficiency can play a very significant role, and it is therefore advisable to think about sufficient supplementation.

Immunity

Zinc deficiency significantly impairs immune function, and this is not only true for a high deficiency of this element – immune problems can occur even with a mild deficiency. Zinc is crucial for the formation and differentiation of T-lymphocytes, but its deficiency also affects other types of immune cells, especially macrophages, neutrophils and NK cells. (18-20)

Colds and respiratory infections

Research suggests that zinc can directly inhibit the binding of viruses in the mucous membranes and their ability to multiply, which is why its use is beneficial for colds and viral infections of the respiratory tract. In several studies, although zinc administration did not alleviate symptoms such as rhinitis, cough or muscle pain, when it was started within 24 hours of the first symptoms, it significantly reduced the duration of illness (20-22).

Several studies have even shown that zinc supplementation can help alleviate the course and symptoms of COVID-19 (29).

Diarrhoea in children

One of the ways that zinc leaves the body is through the stool. Thus, when a person suffers from diarrhea, zinc loss increases. This is very dangerous in infectious diarrhoeal diseases in children, because the zinc deficiency that occurs in these diseases also impairs the body’s ability to cope with the diarrhoea, so that a vicious circle is created. Several clinical studies have shown that dietary zinc supplements reduce the duration and severity of diarrhoeal disease (6).

Macular degeneration

According to some studies, zinc may play a role in the onset and development of age-related macular degeneration, an eye disease that affects the retina and often results in complete blindness. For example, a Dutch population-based study concluded that a high dietary intake of zinc, beta-carotene and vitamins C and E leads to a reduced risk of the disease. In other studies, the administration of zinc to people already suffering from macular degeneration slowed the progression of the disease and in one study even improved visual acuity (20, 23, 24).

Wound healing, tibial ulcers

Zinc is essential for maintaining the integrity of the skin and mucous membranes. Therefore, it is not surprising that people suffering from tibial ulcers very often have low levels of zinc or suffer from abnormal metabolism of this element. Thus, in patients with zinc deficiency, its administration usually leads to an improvement in the condition of tibial ulcers (25-27).

Testosterone, sexuality

Zinc has a direct effect on the testicular cells where the male sex hormone testosterone is produced, and it also blocks the enzyme systems that ensure the conversion of testosterone to estrogen. Thus, its use can increase testosterone levels in the body, but only in men who are zinc deficient (30, 31).

This makes zinc very beneficial for men with erectile dysfunction, where it helps improve both erectile ability and sex drive. However, it can also be useful for premature ejaculation. When zinc deficiency is present in boys during childhood and adolescence, it leads to impaired genital development, called hypogonadism (32- 34, 36).

Fertility

Zinc also has a crucial effect on male fertility, not only due to its influence on testosterone production, but also by promoting the production of seminal fluid, reducing the level of reactive oxygen species and supporting the integrity of the epithelium of the genital organs. The concentration of zinc in the male reproductive organs is significantly higher than in other body tissues, and this element is also essential in several stages of the process of sperm formation and maturation. Thus, zinc deficiency causes a significant reduction in the overall production of sperm and increases the rate of sperm damage. High concentrations of zinc are also found in the “tails” of sperm, where this element is also important for sperm motility. The use of zinc is very effective in smokers with reduced fertility (36).

However, zinc is also important for female fertility – it is necessary for the oocyte, i.e. the germ cell in the ovary, to form and release an egg capable of fertilisation. Zinc deficiency can also seriously impair embryo division and differentiation and cause serious developmental disorders. (37)

Mental performance

Zinc is essential for signal transmission within nerve cells and also between individual nerve cells. It is found in high concentrations especially in the hippocampus, the part of the brain responsible for memory, but also in the cerebral cortex and other areas (38).

Zinc deficiency is very serious in pregnancy, when it can significantly impair the development of the brain and nervous system of the child. In the early stages of pregnancy, it results in severe defects or a reduction in the volume of the cerebellum, while in the last stage (i.e. between 24 and 40 weeks), it tends to result in a deterioration of brain function – the children of these women usually have impaired learning ability, some aspects of memory, but also motor skills. In the last third of pregnancy, the child’s brain undergoes extraordinary structural changes and is very sensitive to zinc deficiency. (38)

Zinc supplementation may also be effective for children with ADHD (attention deficit hyperactivity disorder). Zinc is an essential component of melatonin metabolism, a hormone that (in addition to regulating the sleep cycle) is necessary for the production of the neurotransmitter dopamine, which is usually impaired in ADHD. Moreover, zinc deficiency is common in children with ADHD. (39)

A recent study also suggested that zinc deficiency in early childhood may lead to the development of autism (40).

Weight loss, metabolic syndrome

Another group of people in whom zinc deficiency is extremely common are those who are overweight and obese. One reason for this is probably the relationship between zinc levels and the production of leptin, a hormone produced by adipose tissue that acts on neuropeptide Y (NPY), which in turn regulates food intake in the hypothalamus. However, leptin is also involved in cellular immunity, and its deficiency therefore also increases susceptibility to infection (41).

Zinc is also a good way to prevent metabolic syndrome, a set of factors and changes in the body that significantly increase the risk of cardiovascular disease and diabetes (which includes obesity) (45).

Thyroid gland

Zinc also helps to increase thyroid hormone levels in the body, which is important both in hypofunction of this organ and in weight loss, as thyroid hormones are an important regulator of energy metabolism (42, 43).

Depression

Zinc supplementation has been shown to help reduce depression symptoms (47).

Use and contraindications

The need for zinc varies mainly with age (see table), but may increase in the case of certain health problems, alcoholics, pregnant and lactating women, etc. (17).

On the other hand, taking higher doses is not advisable – one of the reasons is that higher amounts of zinc inhibit the absorption of copper, an element essential for blood formation (on the other hand, higher dietary iron intake inhibits zinc absorption). The use of doses above 60 mg for several weeks has already been shown to reduce the levels of copper-containing enzymes. Longer-term use of doses above 150 mg per day can lead to anaemia, in addition to impaired immunity and a decrease in HDL cholesterol levels. Single doses at 570 mg then even cause severe nausea, diarrhea, vomiting and abdominal cramps. (20)

Possible interactions with certain medications should also be considered when taking zinc. For example, if it is taken with tetracycline or quinolone-based antibiotics, they may interact with each other, resulting in impaired absorption of both zinc and antibiotics. In this case, it is important not to take antibiotics 2 hours before and 4-6 hours after zinc administration. Similarly, zinc reduces the absorption of penicillamine, which is used to treat rheumatoid arthritis – here zinc should be taken no later than two hours before the drug is administered. (20)

On the other hand, increased zinc intake is needed if a person is taking thiazide diuretics, which can increase zinc loss in urine by up to 60% (28).

Suitable combinations

The combination of zinc and magnesium is very suitable, as these two elements mutually increase their absorption and availability, but other combinations are also very effective (46).

Erectile dysfunction, testosterone: zinc + vitamin D3 (35)

Premature ejaculation: zinc + rhodiola + biotin + folic acid (32)

Thyroid: zinc + iodine + selenium (43)

Immunity, colds: zinc + vitamin C (44), zinc + vitamin D3, zinc + EGCG (49), zinc + selenium (51), zinc + magnesium (53)

Metabolic syndrome and diabetes: zinc + ginger (45), zinc + curcumin (48), zinc + magnesium (52)

Depression: zinc + vitamin D3

Weight loss: zinc + curcumin (48)

ADHD: zinc + omega-3 (50)