Epaned Side Effects & Health Impacts

Low zinc status has been linked to a higher risk and faster progression of age-related macular degeneration (AMD), in part because zinc is concentrated in the retina and supports antioxidant defenses there. In the landmark AREDS trial, a supplement formula containing zinc (80 mg as zinc oxide), along with antioxidants, reduced the risk of progression to advanced AMD by about 25% in people with intermediate disease or advanced disease in one eye over roughly 5 years. Other research has shown that inadequate zinc intake is more common in older adults with AMD, reinforcing the idea that maintaining healthy zinc levels may be an important, and often overlooked, strategy for preserving macular health with age.

Research: Smailhodzic D, van Asten F, Blom AM, Mohlin FC, den Hollander AI, van de Ven JPH, et al. (2014) Zinc Supplementation Inhibits Complement Activation in Age-Related Macular Degeneration. PLoS ONE 9(11): e112682. Lengyel D, Török B. Erworbene vorübergehende Nachtblindheit bei Vitamin-A- und Zinkmangel bei Anorexia nervosa neun Jahre nach Nierentransplantation [Acquired temporary night blindness in vitamin A and zinc deficiency in anorexia nervosa nine years after kidney transplantation]. Klin Monbl Augenheilkd. 2006 May;223(5):453-5. German.Blasiak J, Pawlowska E, Chojnacki J, Szczepanska J, Chojnacki C, Kaarniranta K. Zinc and Autophagy in Age-Related Macular Degeneration. Int J Mol Sci. 2020 Jul 15;21(14):4994. Benjamin P. Nicholson, et al. Chapter 37 - Zinc Deficiency and the Eye. Handbook of Nutrition, Diet and the Eye 2014, Pages 371-376.

Zinc deficiency has been associated with a range of neurological and behavioral changes, including increased irritability, poor attention, and slowed cognitive processing. In children, low zinc status has been linked to poorer performance on tests of attention, memory, and school achievement, and some trials have found that zinc supplementation can modestly improve certain cognitive scores, especially in previously deficient populations. Clinically, even mild zinc deficiency may present with subtle symptoms such as mood changes, reduced stress tolerance, and “brain fog,” which can easily be overlooked but may improve when zinc status is corrected.

Research: de Moura JE, de Moura EN, Alves CX, Vale SH, Dantas MM, Silva Ade A, Almeida Md, Leite LD, Brandão-Neto J. Oral zinc supplementation may improve cognitive function in schoolchildren. Biol Trace Elem Res. 2013 Oct;155(1):23-8. Colombo J, Zavaleta N, Kannass KN, Lazarte F, Albornoz C, Kapa LL, Caulfield LE. Zinc supplementation sustained normative neurodevelopment in a randomized, controlled trial of Peruvian infants aged 6-18 months. J Nutr. 2014 Aug;144(8):1298-305. Lee J, Park S and Jang W (2023) Serum zinc deficiency could be associated with dementia conversion in Parkinson’s disease. Front. Aging Neurosci. 15:1132907. Jung A, Spira D, Steinhagen-Thiessen E, Demuth I, Norman K. Zinc Deficiency Is associated With Depressive Symptoms-Results From the Berlin Aging Study II. J Gerontol A Biol Sci Med Sci. 2017 Aug 1;72(8):1149-1154.

Closely linked to reproductive and hormonal problems in both men and women, zinc deficiency can contribute to hypogonadism, low testosterone, reduced sperm count, and menstrual irregularities. In men, low zinc status has been associated with decreased serum testosterone, reduced sperm density and motility, and poorer overall semen quality, while zinc repletion in deficient individuals has been shown to improve some of these parameters. In women, inadequate zinc intake is tied to more frequent cycle disturbances, dysmenorrhea, and potential impacts on ovulation and fertility, underscoring zinc’s important role in healthy hormonal balance and reproductive function.

Research: Zhao J, Dong X, Hu X, Long Z, Wang L, Liu Q, Sun B, Wang Q, Wu Q, Li L. Zinc levels in seminal plasma and their correlation with male infertility: A systematic review and meta-analysis. Sci Rep. 2016 Mar 2;6:22386. Mohan H, Verma J, Singh I, Mohan P, Marwah S, Singh P. Inter-relationship of zinc levels in serum and semen in oligospermic infertile patients and fertile males. Indian J Pathol Microbiol. 1997 Oct;40(4):451-5. PMID: 9444854. Zečević N, Veselinović A, Perović M, Stojsavljević A. Association Between Zinc Levels and the Impact of Its Deficiency on Idiopathic Male Infertility: An Up-to-Date Review. Antioxidants (Basel). 2025 Jan 29;14(2):165. Dhar S, Yadav R, Tomar A. Serum Zinc Levels in Women with Polycystic Ovarian Syndrome are Lower as Compared to Those without Polycystic Ovarian Syndrome: A Cohort Study. J Hum Reprod Sci. 2024 Jan-Mar;17(1):25-32.

Zinc deficiency impairs immune defenses by reducing T‑cell activity and weakening resistance to infection. Low zinc levels increase susceptibility to recurrent infections, especially respiratory illnesses such as the common cold, bronchitis, and pneumonia. Clinical studies show that zinc supplementation can strengthen immune response and lower mortality when used alongside standard treatment for severe pneumonia. In a placebo‑controlled trial in elderly participants, zinc supplementation decreased the incidence of infections by 66% and improved cell‑mediated immunity.

Research: Shah UH, Abu-Shaheen AK, Malik MA, Alam S, Riaz M, Al-Tannir MA. The efficacy of zinc supplementation in young children with acute lower respiratory infections: a randomized double-blind controlled trial. Clin Nutr. 2013 Apr;32(2):193-9. Prasad AS. Zinc: role in immunity, oxidative stress and chronic inflammation. Curr Opin Clin Nutr Metab Care. 2009 Nov;12(6):646-52. Wang L, Song Y. Efficacy of zinc given as an adjunct to the treatment of severe pneumonia: A meta-analysis of randomized, double-blind and placebo-controlled trials. Clin Respir J. 2018 Mar;12(3):857-864. Marianna K. Baum, Shenghan Lai, Sabrina Sales, J. Bryan Page, Adriana Campa, Randomized, Controlled Clinical Trial of Zinc Supplementation to Prevent Immunological Failure in HIV-Infected Adults, Clinical Infectious Diseases, Volume 50, Issue 12, 15 June 2010, Pages 1653–1660.

Zinc deficiency during childhood and adolescence is strongly linked to impaired linear growth and delayed sexual maturation, and is a recognized contributor to stunting in many low‑ and middle‑income countries. In some population studies, zinc deficiency has been present in over 30–40% of children, and zinc supplementation programs have been associated with modest but meaningful improvements in height gain over time. Clinically, even marginal zinc deficiency can quietly slow growth velocity and pubertal progression, making adequate zinc intake an important, often overlooked pillar of healthy growth and development.

Research: Abdollahi M, Ajami M, Abdollahi Z, Kalantari N, Houshiarrad A, Fozouni F, Fallahrokni A, Mazandarani FS. Zinc supplementation is an effective and feasible strategy to prevent growth retardation in 6 to 24 month children: A pragmatic double blind, randomized trial. Heliyon. 2019 Nov 1;5(11):e02581. Walravens PA, Krebs NF, Hambidge KM. Linear growth of low income preschool children receiving a zinc supplement. Am J Clin Nutr. 1983 Aug;38(2):195-201. Rerksuppaphol S, Rerksuppaphol L. Zinc supplementation enhances linear growth in school-aged children: A randomized controlled trial. Pediatr Rep. 2018 Jan 4;9(4):7294. Zinc deficiency as risk factor for stunting among children aged 2-5 years. (2017). Universa Medicina, 36(1), 11-18.

Zinc deficiency often first shows up on the skin, with acrodermatitis‑like eruptions around the mouth, perineum, and distal extremities, accompanied by alopecia and sometimes nail changes. Characteristic lesions can be erythematous, scaly, or pustular, and both congenital and acquired zinc deficiency states have been reported to improve dramatically within days to weeks of adequate zinc repletion. Clinically, zinc is also crucial for normal collagen synthesis and immune function in the skin, so deficiency is linked to delayed wound healing and weaker scars, whereas restoring zinc status can enhance re‑epithelialization and reduce wound complications.

Research: Kelly S, Stelzer JW, Esplin N, Farooq A, Karasik O. Acquired Acrodermatitis Enteropathica: A Case Study. Cureus. 2017 Sep 8;9(9):e1667. Alwadany MM, Al Wadani AF, Almarri FH, Alyami HS, Al-Subaie MA. Acrodermatitis Enteropathica: A Rare Case With Lifelong Implications. Cureus. 2023 Apr 18;15(4):e37783. Al-Khafaji Z, Brito S, Bin BH. Zinc and Zinc Transporters in Dermatology. Int J Mol Sci. 2022 Dec 18;23(24):16165. Ogawa Y, Kinoshita M, Shimada S, Kawamura T. Zinc and Skin Disorders. Nutrients. 2018 Feb 11;10(2):199.

In many patients, inadequate zinc status affects the gastrointestinal tract, contributing to chronic or recurrent diarrhea, anorexia, and characteristic changes in taste (hypogeusia) and smell (hyposmia) that further suppress intake. Clinical studies in children with acute and persistent diarrhea have shown that zinc supplementation shortens illness duration and reduces subsequent diarrheal episodes, underscoring how low zinc status both results from and perpetuates gut losses. The practical implication is that, when patients present with otherwise unexplained diarrhea, poor appetite, and altered taste or smell, especially in the setting of malabsorption, restrictive diets, or chronic illness, evaluating and correcting zinc deficiency can be an important step in breaking this cycle and restoring nutritional and gastrointestinal health.

Research: Mozaffar B, Ardavani A, Muzafar H, Idris I. The Effectiveness of Zinc Supplementation in Taste Disorder Treatment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Nutr Metab. 2023 Mar 8;2023:6711071. Heckmann SM, Hujoel P, Habiger S, Friess W, Wichmann M, Heckmann JG, Hummel T. Zinc gluconate in the treatment of dysgeusia--a randomized clinical trial. J Dent Res. 2005 Jan;84(1):35-8. Mahajan SK, Prasad AS, Lambujon J, Abbasi AA, Briggs WA, McDonald FD. Improvement of uremic hypogeusia by zinc: a double-blind study. Am J Clin Nutr. 1980 Jul;33(7):1517-21. Aliani M, Udenigwe CC, Girgih AT, Pownall TL, Bugera JL, Eskin MN. Zinc deficiency and taste perception in the elderly. Crit Rev Food Sci Nutr. 2013;53(3):245-50. Tanaka H, Mori E, Yonezawa N, Sekine R, Nagai M, Tei M, Otori N. Efficacy of Normalising Serum Zinc Level for Patients with Olfactory Dysfunction and Zinc Deficiency. ORL J Otorhinolaryngol Relat Spec. 2024;86(2):73-81.