THE POTENTIAL BENEFITS OF ZINC SUPPLEMENTS

THE POTENTIAL BENEFITS OF ZINC SUPPLEMENTS

Zinc is a trace element that is required for living organisms and their biological processes. Because the body cannot accumulate zinc, it is essential to take this element consistently in the diet ^[1].  In the human body, zinc is found in muscles (60%), bones (30%) and skin (5%). Zinc is involved in the activation of various enzymes and proteins, and it aids in the absorption of vitamins A, E, and folate. Low levels of zinc can be associated with an increased chance of developing infections and degenerative pathologies. Zinc also plays an important role in the psychosocial functioning of human behavior ^[2].

Zinc deficiency defined by a plasmic zinc level below 60 µg/dl, exceeds the regulatory capacity of homeostatic mechanisms, clinical symptoms may arise. Zinc deficiency can occur due to inadequate intake, reduced absorption, increased losses, or increased demand. It can also occur due to genetic disorders such as Acrodermatitis enteropathica and sickle cell disease. Inadequate intakes as a result of a zinc-deficient diet or a phytate rich diet is the most common worldwide cause of zinc deficiency. Individuals most susceptible to zinc deficiency caused by inadequate intake are those with the greatest physiological demand. Due to age-related declines in absorption and poor diet, the elderly is particularly at risk ^[3].

Bullous-pustular dermatitis, alopecia, diarrhea, weight loss, intercurrent infections, and hypogonadism are all symptoms of severe zinc insufficiency in males. Unrecognized severe zinc deficiency is fatal. Growth retardation, delayed puberty, hypogonadism in males, rough skin, poor appetite, delayed wound healing, and abnormalities in gustation, olfaction, and night vision are all symptoms of moderate zinc deficiency. Oligospermia, weight loss, and hyperammonemia are all symptoms of mild zinc deficiency ^[3].

THE BENEFITS OF ZINC SUPPLEMENT

Acne Vulgaris

Since Michaelsson discovered zinc’s beneficial effect on acne in a patient with acrodermatitis enteropathica, and subsequent studies demonstrated low serum zinc in acne patients, zinc has been widely used both topically and systemically for the treatment of acne vulgaris. Oral zinc sulfate is reportedly more effective in the treatment of severe acne than for the treatment of mild to moderate acne but nausea, vomiting, and diarrhea occur frequently. Oral zinc gluconate has also been reported to be effective in the treatment of inflammatory acne, but the initial loading dose is ineffective. However, acne treatment with zinc salts appears to be equal or less effective compared with systemic tetracyclines (minocycline, oxytetracycline). The exact mechanism of zinc in acne treatment remains poorly elucidated and is considered to act directly on microbial inflammatory equilibrium and facilitate antibiotic absorption when used in combination. Another mechanism for zinc’s acne benefit is its antiandrogenic action, which suppresses sebum production ^[4].

Alopecia

Androgenetic alopecia is a prevalent condition in males over the age of 20, with an estimated 90% of males over the age of 20 experiencing some degree of frontal recession. The mainstay of treatment is minoxidil and finasteride, as well as surgical methods like hair transplantation. Zinc has been discovered to have antiandrogen properties and to alter the activities of 5𝛼-reductase types 1 and 2 ^[4].

Immunity

Zinc is a trace element that is required for the activity of several enzymes and transcription factors in humans. It plays a key role in regulating the function of both the adaptive and the innate immune system. Dietary sources of zinc are animal products such as meat, fish, eggs, and dairy, but it is also contained in whole grains, nuts, and legumes. When compared to zinc obtained from plant products, zinc from animal sources has a higher bioavailability. Phytate, some dietary fibers, and lignin are plant ligands that chelate zinc and prevent it from being absorbed ^[5].

Zinc’s effect on the immune system is complex; it can promote and inhibit various immunological activities to achieve a proper balance of pro and anti-inflammatory effects via a variety of methods. A correct intake of zinc is essential to limit the overproduction of inflammatory cytokines: in vitro and human studies show that zinc deficiency is associated with an increased inflammatory response and excessive release of pro inflammatory cytokines such as IL-2, IL-6, and TNF-alfa, regulated through the NF-κB signaling pathway. Zinc also enhances the number of inducible regulatory T cells. Another important role played by zinc is the maintenance of membrane barrier integrity, which is essential in the pulmonary and intestinal epithelia that constitute the first barrier to protect the organism from pathogens. Zinc supplementation has also been proven to have a direct antiviral effect on RSV, Dengue virus, and coronaviruses, as well as reducing oxidative stress and minimizing the duration of cold symptoms in adults. Lastly, some authors suggested that combining chloroquine with zinc would increase the toxicity of chloroquine against viruses ^[5].

Zinc supplementation has also been investigated against acute lower respiratory infection. Two studies found that zinc therapy decreased infection episodes and increased recovery rates from illness and fever, however the latter study’s effect was only significant in boys. Lower respiratory infection may be caused by a variety of bacteria or viruses, the nature of which was not explored in these studies. Hence it can be concluded that zinc treatment reduces the symptoms, but there is no evidence that zinc has an effect on the immune response to the underlying infections based on these findings. A pooled analysis of four trials in which continuous supplementation was investigated confirmed that zinc is efficient for the prevention of pneumonia. In this study, zinc supplementation reduced the incidence of pneumonia in children in developing countries by 41%. Pneumonia is a major cause of childhood mortality; it accounts for approximately 20% of childhood deaths in developing countries, making zinc supplementation a promising approach for a significant reduction in childhood mortality. Furthermore, a recent study suggests that zinc may be beneficial to the elderly. Zinc supplementation was found to be associated with a lower risk of pneumonia in nursing home residents, suggesting that zinc supplementation could be used to prevent pneumonia in the elderly ^[6].

Wound Healing

Zinc, a trace mineral, is found to be in low concentration in tissues and across cell membranes in post-neurosurgical wound-healing patients. As such, zinc is firmly regulated through gene transcription rule, ion carriers, cellular homeostasis, and extracellular supplies. Extracellular vesicles contain a modest amount of zinc during physiological processes. Zinc is normally taken up by the zinc transporter protein (ZIP) in intracellular vesicles. The cytosol contains free zinc ions, which have been identified as secondary messengers capable of targeting proteins to regulate a variety of chemical and physiological pathways. Therefore, the availability of zinc and its regulation are essential components of cellular physiology ^[7].

Zinc shortage has been blamed for delays in wound healing. Zinc deficiency plays a role in inflammation by increasing the inflammatory response and causing damage to the host tissue. Post-neurosurgical and severely ill patients, patients with severe burn injury, hypodermic sore, insignificant surgery, and pressure ulcers have all received zinc supplements ^[7].

INTERACTION

Zinc–Iron

Studies showed that high concentrations of iron can have a negative effect on zinc absorption in human adults when zinc and iron are given in solution and on an empty stomach. It has been suggested that suppression of zinc absorption by iron occurs when given in an aqueous medium because of a competition for common nonspecific pathways. This suppression cannot occur when iron and zinc are given during a meal because zinc can be absorbed via an alternate pathway with the aid of ligands formed during protein digestion ^[8].

Zinc–Vitamins

Finally, the interaction of zinc with some vitamins (A, D, and E) is intriguing because zinc influences the vitamins’ trans-porters, such as retinol-binding protein for vitamin A and tocopherol for vitamin E. The interaction between zinc and vitamin D is suggestive because zinc participates in the constitution of vitamin D (especially D3 isoform) receptor DNA binding domain through two zinc finger-like motifs, favoring the re-absorption of calcium at kidney level and phosphorus at intestinal level. As a result, the interaction of zinc and vitamin D is critical for the proper functioning of a variety of organs and tissues, including the brain and bone ^[8].

Zinc–Calcium

Although different mechanisms of zinc and calcium absorption in small intestine have been proposed through the binding with prostaglandin E and vitamin D, respectively, experiments in rats have however shown that calcium may interfere in intestinal zinc absorption because a competition between zinc and calcium for the same transcellular transporting carriers on the mem-brane surface occurs ^[8].

REFERENCES

1. Sanna A, Firinu D, Zavattari P, Valera P. Zinc Status and Autoimmunity: A Systematic Review and Meta-Analysis. Nutrients. [Internet]. 2018 [cited 2022 Feb 1]; 10: 1-17. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793296/
2. Uwitonze AM, Ojeh N, Murererehe J, Atfi A, Razzaque MS. Zinc Adequacy Is Essential for the Maintenance of Optimal Oral Health. Nutrients. [Internet]. 2020 [cited 2022 Feb 1]; 12: 1-14. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/
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3. Kogan S, Sood A, Garnick MS. Zinc and Wound Healing: A Review of Zinc Physiology and Clinical Applications. Wounds. [Internet]. 2017 [cited 2022 Feb 1]; 29: 102-6. Available form: http://www.hmpgloballearningnetwork.com/site/wounds/
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4. Gupta M, Mahajan VK, Mehta KS, Chauhan PS. Zinc therapy in dermatology: a review. Dermatology Research and Practice. [Internet]. 2014 [cited 2022 Feb 1]; 2014: Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120804/
5. Pecora F, Persico F, Argentiero A, Neglia C, Esposito S. The Role of Micronutrients in Support of the Immune Response against Viral Infections. Nutrients. [Internet]. 2020 [cited 2022 April 21]; 12: 1-45. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589163/
6. Overbeck S, Rink L, Haase H. Modulating the immune response by oral zinc supplementation: a single approach for multiple diseases. Archivum Immunologiae et Therapiae Experimentalis. [Internet]. 2008 [cited 2022 April 21]; 56: 15-30. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079749/
7. Adjepong D, Jahangir S, Malik B. The Effect of Zinc on Post-Neurosurgical Wound Healing: A Review. Cureus. [Internet]. 2020 [cited 2022 April 21]; 12: 1-7. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039353/
8. Mocchegiani E, Romeo J, Malavolta M, Costarelli L, Giacconi R, Diaz LE, Marcos A. Zinc: dietary intake and impact of supplementation on immune function in elderly. Age (Dordr). [Internet]. 2013 [cited 2022 Feb 1]; 35: 839-60. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636409/