What is it?

Description

Zinc is an essential micronutrient that binds to approximately 2,800 human proteins for catabolic, structural, and regulatory functions. (102) It is involved as a signaling molecule in a vast number of physiological processes and plays a structural role in 10% of all mammalian proteins. It acts as a regulator of gene expression and homeostasis, as well as an anti-inflammatory and anti-oxidative agent. (6)(139) Zinc plays important roles in the growth and health of connective tissues (e.g., bone, hair, skin, tendons, skin), the nervous system, cognition, and immunity. (12)(131)  

Low zinc levels may be associated with various auto-immune disorders, (32)(101)(137)(153) cardiovascular disorders, (71)(97)(175) cognitive and neurodegenerative disorders, (11)(23)(134)(152)(155) connective tissue disorders such as acne (171) and osteoporosis, (29) endocrine disorders including polycystic ovarian syndrome (1) and type II diabetes, (56) and male infertility (176) and prostatitis. (36) 

High levels of exercise, (34) vegetarian diets, and the use of anti-hypertensive medications (22) may lead to low zinc status, and thus supplementation or fortification may be required. (58) The recommended intakes of elemental zinc from the diet are approximately 11 mg for adult males and 8 mg for females, (111) though daily pharmacological doses are much higher, often ranging between 30 to 150 mg. (139) It should be noted that excess intake of zinc may lead to copper deficiencies, (104) making it important for clinicians to be aware of how to recommend zinc for short-term therapeutic purposes versus for maintaining zinc levels.

Please note that this review focuses on the provision of zinc in oral supplementation forms only. Dosing and administration are provided below using the elemental amount of zinc found in supplements and not the total weight of a zinc compound.

For a review of the applications of topical zinc in dermatology, please see Zinc Therapy in Dermatology: A Review. (67)

Main uses

Antioxidation, anti-inflammation
Cardiometabolic health
Immune health, common cold, and infection
Depression
Pediatric diarrhea
Prenatal support and growth
Skin, mucosal lining, and wound healing

Formulations

Form
Characteristics
Zinc bisglycinate
Contains 31% elemental zinc
Zinc bisglycinate was 43.4% more bioavailable than zinc gluconate (61)
Zinc acetate
Contains 30% elemental zinc
Zinc acetate was 43% more bioavailable than zinc oxide and more than 5.8x more bioavailable in states of hypochloridia (75)
Possesses strong astringent taste (163)
Zinc citrate
Contains 34% elemental zinc
Provided equal bioavailability to zinc gluconate, (15) but without the astringent taste and odor, and at a cheaper price. Zinc citrate had a 11% greater absorption than zinc oxide (163)
Zinc picolinate
Contains 21% elemental zinc
Provided greater absorption than zinc citrate or zinc gluconate, but serum zinc did not rise significantly (15)
Zinc gluconate
Contains 14% elemental zinc
Provides equal bioavailability to zinc citrate, (15) but may possess an astringent taste and be higher priced (due to low elemental zinc content)
Zinc gluconate had 8-11% greater absorption than zinc oxide (146)(163)
Zinc methionine
Contains 18% elemental zinc
Zinc methionine was 25% more bioavailable than zinc sulfate (132)
Zinc sulfate
Contains 23% elemental zinc
Zinc sulfate was 26% more bioavailable than zinc oxide (167)
Possesses strong astringent taste, but is inexpensive (163)
Zinc ascorbate
Contains 16% elemental zinc
Zinc ascorbate was equally bioavailable to zinc sulfate (132)
Zinc oxide
Contains 80% elemental zinc
Very low cost, but least absorbable with -11% difference compared to zinc citrate or gluconate (163)
Zinc carnosine
Contains 23% elemental zinc
Also known as Polaprezinc
Zinc aspartate
Contains 20% elemental zinc

Dosing & administration

Adverse effects

The proportion of individuals reporting adverse events from zinc supplementation may be higher in treatment groups than placebos (24-58% higher risk). This may include higher risk for experiencing bad taste (65-130%) and nausea (64-115%), but no difference for abdominal pain, constipation, diarrhea, dry mouth, or oral irritation compared to placebo was reported. (143)(147)(171) However, the use of zinc supplements at normal therapeutic doses is unlikely to cause any long-term harm. (72) In children requiring supplementation for diarrhea reduction, zinc may increase the risk of vomiting (20-94%). (60)(93)(96)(105) Zinc gluconate produced a higher frequency of vomiting than zinc sulfate or acetate in one analysis. (100)

Zinc may reduce copper retention (57) and iron absorption. (116)(117) For copper, case reports of zinc-induced copper deficiencies exist at excessively high doses (e.g., 120-180 mg over seven months to an infant, or up to 600 mg per day in adults). (19)(166) Lower level dosing does not seem to impact copper status. (17)(85)(140)(169) For iron, even modest doses of zinc can reduce iron status. (27)(43)(49) However, the risk for anemia as a result of these micronutrient deficiencies does not appear to increase between zinc doses of 10-20 mg for up to 15 months. (46)

Pharmacokinetics

Absorption

  • Between 26-34% of ingested zinc is absorbed in the small intestine (duodenum and jejunum) via transporters, including Zrt-, Irt-like protein 4 (ZIP4), and zinc transporter 1 (ZnT-1), and via passive diffusion (at high concentrations) (102)(131)
  • Aqueous zinc solutions may be better absorbed (60-70%) than solid foods (102)(131)
  • Zinc may be more efficiently absorbed in states in which greater amounts of zinc are required, such as in states of deficiency, pregnancy and lactation, and infancy (102)(131)
  • Nutritional factors such as the presence of animal proteins or citrate improve absorption, whereas reduced absorption may occur with ingestion of phytate (reduced absorption 45%; found in plant seeds, grains, and legumes), fiber, calcium, and iron (16)(102)(131)

Distribution

  • Post-absorption, zinc is moved into circulation and bound to albumin (60-70%), α-macroglobulin (30%), and transferrin (10%) for transport to various tissues (102)(131)
  • The human body contains approximately 2.6 g of zinc, found in skeletal muscle (50-57%), bone (29-36%), skin (4-6%), liver (3-5%), blood (1.5%), intestines (1.2%), brain (0.6-1.5%), kidneys (0.6-0.7%), lung (0.5%), stomach (0.5%), heart (0.3%), hair and nails (0.1-0.5%), spleen (0.1%), and eyes (<0.01%); however, this is not indicative of biological activity at these sites (102)(139)
  • For example, seminal plasma contains relatively very little zinc (0.08-0.27 mg/mL), but zinc is known to benefit various sperm parameters (48)(139)

Metabolism

  • Homeostatic balance is achieved via quick adjustments to zinc absorption or excretion depending on states of deficiency or excess (102)(131)
  • Intracellularly, zinc is bound to metallothionein proteins, which act as a reservoir to release zinc when needed and prevent cellular toxicity from an excessive presence of zinc (12)
  • Zinc may be removed from the tightly regulated intracellular environment by other ZIP and ZnT transporters (102)

Excretion

  • Approximately 50% of zinc is excreted into the feces (6.0-22.4 mg/day) via biliary and intestinal secretions (131)
  • However, zinc can be excreted in the urine (0.3-6.5 mg/day) or via losses of skin (0.29-0.67 mg/day), hair (30 mcg/day), semen (0.09-0.63 mg/day), menstruation (0.4-0.6 mcg/day), or sweat (0.5 mg/day) (16)(131)
References
  1. Abedini, M., Ghaedi, E., Hadi, A., Mohammadi, H., & Amani, R. (2019). Zinc status and polycystic ovarian syndrome: A systematic review and meta-analysis. Journal of Trace Elements in Medicine and Biology, 52, 216–221. https://doi.org/10.1016/j.jtemb.2019.01.002 
  2. Abioye, A. I., Bromage, S., & Fawzi, W. (2021). Effect of micronutrient supplements on influenza and other respiratory tract infections among adults: A systematic review and meta-analysis. BMJ Global Health, 6(1). https://doi.org/10.1136/bmjgh-2020-003176 
  3. Aggarwal, R., Sentz, J., & Miller, M. A. (2007). Role of zinc administration in prevention of childhood diarrhea and respiratory illnesses: A meta-analysis. Pediatrics, 119(6), 1120–1130. https://doi.org/10.1542/peds.2006-3481 
  4. Akhondzadeh, S., Mohammadi, M.-R., & Khademi, M. (2004). Zinc sulfate as an adjunct to methylphenidate for the treatment of attention deficit hyperactivity disorder in children: A double blind and randomized trial [ISRCTN64132371]. BMC Psychiatry, 4, 9. https://doi.org/10.1186/1471-244X-4-9 
  5. Al-Kaisy, A. A., Salih Sahib, A., & Al-Biati, H. A. H. K. (2006). Effect of zinc supplement in the prognosis of burn patients in iraq. Annals of Burns and Fire Disasters, 19(3), 115–122. https://www.ncbi.nlm.nih.gov/pubmed/21991035 
  6. Anzellotti, A. I., & Farrell, N. P. (2008). Zinc metalloproteins as medicinal targets. Chemical Society Reviews, 37(8), 1629–1651. https://doi.org/10.1039/b617121b 
  7. Appenzeller-Herzog, C., Mathes, T., Heeres, M. L. S., Weiss, K. H., Houwen, R. H. J., & Ewald, H. (2019). Comparative effectiveness of common therapies for Wilson disease: A systematic review and meta-analysis of controlled studies. Liver International: Official Journal of the International Association for the Study of the Liver, 39(11), 2136–2152. https://doi.org/10.1111/liv.14179 
  8. Arbabi-kalati, F., Arbabi-kalati, F., Deghatipour, M., & Ansari Moghadam, A. (2012). Evaluation of the efficacy of zinc sulfate in the prevention of chemotherapy-induced mucositis: A double-blind randomized clinical trial. Archives of Iranian Medicine, 15(7), 413–417. https://doi.org/012157/AIM.008 
  9. Asbaghi, O., Sadeghian, M., Fouladvand, F., Panahande, B., Nasiri, M., Khodadost, M., Shokri, A., Pirouzi, A., & Sadeghi, O. (2020). Effects of zinc supplementation on lipid profile in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials. Nutrition, Metabolism, and Cardiovascular Diseases, 30(8), 1260–1271. https://doi.org/10.1016/j.numecd.2020.03.021 
  10. Azizollahi, G., Azizollahi, S., Babaei, H., Kianinejad, M., Baneshi, M. R., & Nematollahi-mahani, S. N. (2013). Effects of supplement therapy on sperm parameters, protamine content and acrosomal integrity of varicocelectomized subjects. Journal of Assisted Reproduction and Genetics, 30(4), 593–599. https://doi.org/10.1007/s10815-013-9961-9 
  11. Babaknejad, N., Sayehmiri, F., Sayehmiri, K., Mohamadkhani, A., & Bahrami, S. (2016). The relationship between zinc levels and autism: A systematic review and meta-analysis. Iranian Journal of Child Neurology, 10(4), 1–9. https://www.ncbi.nlm.nih.gov/pubmed/27843460 
  12. Baltaci, A. K., Yuce, K., & Mogulkoc, R. (2018). Zinc metabolism and metallothioneins. Biological Trace Element Research, 183(1), 22–31. https://doi.org/10.1007/s12011-017-1119-7 
  13. Bao, B., Prasad, A. S., Beck, F. W. J., Fitzgerald, J. T., Snell, D., Bao, G. W., Singh, T., & Cardozo, L. J. (2010). Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: A potential implication of zinc as an atheroprotective agent. The American Journal of Clinical Nutrition, 91(6), 1634–1641. https://doi.org/10.3945/ajcn.2009.28836 
  14. Barnett, J. B., Dao, M. C., Hamer, D. H., Kandel, R., Brandeis, G., Wu, D., Dallal, G. E., Jacques, P. F., Schreiber, R., Kong, E., & Meydani, S. N. (2016). Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly: A randomized, double-blind, placebo-controlled trial. The American Journal of Clinical Nutrition, 103(3), 942–951. https://doi.org/10.3945/ajcn.115.115188 
  15. Barrie, S. A., Wright, J. V., Pizzorno, J. E., Kutter, E., & Barron, P. C. (1987). Comparative absorption of zinc picolinate, zinc citrate and zinc gluconate in humans. Agents and Actions, 21(1-2), 223–228. https://doi.org/10.1007/BF01974946 
  16. Bel-Serrat, S., Stammers, A.-L., Warthon-Medina, M., Moran, V. H., Iglesia-Altaba, I., Hermoso, M., Moreno, L. A., Lowe, N. M., & EURRECA Network. (2014). Factors that affect zinc bioavailability and losses in adult and elderly populations. Nutrition Reviews, 72(5), 334–352. https://doi.org/10.1111/nure.12105 
  17. Bertinato, J., Simpson, J. R., Sherrard, L., Taylor, J., Plouffe, L. J., Van Dyke, D., Geleynse, M., Dam, Y. Y., Murphy, P., Knee, C., Vresk, L., Holland, N., Quach, H., Mack, D. R., Cooper, M., L’abbé, M. R., & Hayward, S. (2013). Zinc supplementation does not alter sensitive biomarkers of copper status in healthy boys. The Journal of Nutrition, 143(3), 284–289. https://doi.org/10.3945/jn.112.171306 
  18. Bilici, M., Yildirim, F., Kandil, S., Bekaroğlu, M., Yildirmiş, S., Değer, O., Ulgen, M., Yildiran, A., & Aksu, H. (2004). Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 28(1), 181–190. https://doi.org/10.1016/j.pnpbp.2003.09.034 
  19. Botash, A. S., Nasca, J., Dubowy, R., Weinberger, H. L., & Oliphant, M. (1992). Zinc-induced copper deficiency in an infant. American Journal of Diseases of Children , 146(6), 709–711. https://doi.org/10.1001/archpedi.1992.02160180069019 
  20. Brandt, S. (2013). The clinical effects of zinc as a topical or oral agent on the clinical response and pathophysiologic mechanisms of acne: A systematic review of the literature. Journal of Drugs in Dermatology, 12(5), 542–545. https://www.ncbi.nlm.nih.gov/pubmed/23652948 
  21. Braud, A., & Boucher, Y. (2020). Taste disorder’s management: A systematic review. Clinical Oral Investigations, 24(6), 1889–1908. https://doi.org/10.1007/s00784-020-03299-0 
  22. Braun, L. A., & Rosenfeldt, F. (2013). Pharmaco-nutrient interactions - A systematic review of zinc and antihypertensive therapy. International Journal of Clinical Practice, 67(8), 717–725. https://doi.org/10.1111/ijcp.12040 
  23. Bredholt, M., & Frederiksen, J. L. (2016). Zinc in multiple sclerosis: A systematic review and meta-analysis. ASN Neuro, 8(3). https://doi.org/10.1177/1759091416651511 
  24. Brown, K. H., Peerson, J. M., Rivera, J., & Allen, L. H. (2002). Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: A meta-analysis of randomized controlled trials. The American Journal of Clinical Nutrition, 75(6), 1062–1071. https://doi.org/10.1093/ajcn/75.6.1062 
  25. Brown, N., Kukka, A. J., & Mårtensson, A. (2020). Efficacy of zinc as adjunctive pneumonia treatment in children aged 2 to 60 months in low-income and middle-income countries: A systematic review and meta-analysis. BMJ Paediatrics Open, 4(1), e000662. https://doi.org/10.1136/bmjpo-2020-000662 
  26. Capdor, J., Foster, M., Petocz, P., & Samman, S. (2013). Zinc and glycemic control: A meta-analysis of randomised placebo controlled supplementation trials in humans. Journal of Trace Elements in Medicine and Biology , 27(2), 137–142. https://doi.org/10.1016/j.jtemb.2012.08.001 
  27. Carter, R. C., Kupka, R., Manji, K., McDonald, C. M., Aboud, S., Erhardt, J. G., Gosselin, K., Kisenge, R., Liu, E., Fawzi, W., & Duggan, C. P. (2018). Zinc and multivitamin supplementation have contrasting effects on infant iron status: A randomized, double-blind, placebo-controlled clinical trial. European Journal of Clinical Nutrition, 72(1), 130–135. https://doi.org/10.1038/ejcn.2017.138 
  28. Castillo-Durán, C., Marı́n, V. B., Alcázar, L. S., Iturralde, H., & Ruz, M. O. (2001). Controlled trial of zinc supplementation in Chilean pregnant adolescents. Nutrition Research , 21(5), 715–724. https://doi.org/10.1016/S0271-5317(01)00285-8 
  29. Ceylan, M. N., Akdas, S., & Yazihan, N. (2021). Is zinc an important trace element on bone-related diseases and complications? A meta-analysis and systematic review from serum level, dietary intake, and supplementation aspects. Biological Trace Element Research, 199(2), 535–549. https://doi.org/10.1007/s12011-020-02193-w 
  30. Chaffee, B. W., & King, J. C. (2012). Effect of zinc supplementation on pregnancy and infant outcomes: A systematic review. Paediatric and Perinatal Epidemiology, 26 Suppl 1, 118–137. https://doi.org/10.1111/j.1365-3016.2012.01289.x 
  31. Chaitanya, N. C., Shugufta, K., Suvarna, C., Bhopal, T., Mekala, S., Ponnuru, H., Madathanapalle, R., Patel, M., Abhyankar, S., Reddy, C., & Deveneni, P. (2019). A meta-analysis on the efficacy of zinc in oral mucositis during cancer chemo and/or radiotherapy-an evidence-based approach. Journal of Nutritional Science and Vitaminology, 65(2), 184–191. https://doi.org/10.3177/jnsv.65.184 
  32. Chen, M., Sun, Y., & Wu, Y. (2020). Lower circulating zinc and selenium levels are associated with an increased risk of asthma: Evidence from a meta-analysis. Public Health Nutrition, 23(9), 1555–1562. https://doi.org/10.1017/S1368980019003021 
  33. Chi, W. J., Myers, J. N., Frank, S. J., Aponte-Wesson, R. A., Otun, A. O., Nogueras-González, G. M., Li, Y., Geng, Y., & Chambers, M. S. (2020). The effects of zinc on radiation-induced dysgeusia: A systematic review and meta-analysis. Supportive Care in Cancer, 28(12), 1–12. https://doi.org/10.1007/s00520-020-05578-8 
  34. Chu, A., Holdaway, C., Varma, T., Petocz, P., & Samman, S. (2018). Lower serum zinc concentration despite higher dietary zinc intake in athletes: A systematic review and meta-analysis. Sports Medicine , 48(2), 327–336. https://doi.org/10.1007/s40279-017-0818-8 
  35. Cruz, K. J. C., Morais, J. B. S., de Oliveira, A. R. S., Severo, J. S., & Marreiro, D. do N. (2017). The effect of zinc supplementation on insulin resistance in obese subjects: A systematic review. Biological Trace Element Research, 176(2), 239–243. https://doi.org/10.1007/s12011-016-0835-8 
  36. Cui, D., Han, G., Shang, Y., Mu, L., Long, Q., & Du, Y. (2015). The effect of chronic prostatitis on zinc concentration of prostatic fluid and seminal plasma: A systematic review and meta-analysis. Current Medical Research and Opinion, 31(9), 1763–1769. https://doi.org/10.1185/03007995.2015.1072707 
  37. Czlonkowska, A., Gajda, J., & Rodo, M. (1996). Effects of long-term treatment in Wilson’s disease with D-penicillamine and zinc sulphate. Journal of Neurology, 243(3), 269–273. https://doi.org/10.1007/BF00868525 
  38. D’Cruze, H., Arroll, B., & Kenealy, T. (2009). Is intranasal zinc effective and safe for the common cold? A systematic review and meta-analysis. Journal of Primary Health Care, 1(2), 134–139. https://www.ncbi.nlm.nih.gov/pubmed/20690364 
  39. da Silva, L. E. M., de Santana, M. L. P., Costa, P. R. de F., Pereira, E. M., Nepomuceno, C. M. M., Queiroz, V. A. de O., de Oliveira, L. P. M., Machado, M. E. P. da C.-, & de Sena, E. P. (2021). Zinc supplementation combined with antidepressant drugs for treatment of patients with depression: A systematic review and meta-analysis. Nutrition Reviews, 79(1), 1–12. https://doi.org/10.1093/nutrit/nuaa039 
  40. Danesh, A., Janghorbani, M., & Mohammadi, B. (2010). Effects of zinc supplementation during pregnancy on pregnancy outcome in women with history of preterm delivery: A double-blind randomized, placebo-controlled trial. The Journal of Maternal-Fetal & Neonatal Medicine, 23(5), 403–408. https://doi.org/10.1080/14767050903165214 
  41. Darmstadt, G. L., Osendarp, S. J. M., Ahmed, S., Feldman, C., Van Raaij, J. M. A., Baqui, A. H., Hautvast, J. G. A. J., & Fuchs, G. J. (2012). Effect of antenatal zinc supplementation on impetigo in infants in Bangladesh. The Pediatric Infectious Disease Journal, 31(4), 407–409. https://doi.org/10.1097/INF.0b013e318243e232 
  42. Davison, G., Marchbank, T., March, D. S., Thatcher, R., & Playford, R. J. (2016). Zinc carnosine works with bovine colostrum in truncating heavy exercise-induced increase in gut permeability in healthy volunteers. The American Journal of Clinical Nutrition, 104(2), 526–536. https://doi.org/10.3945/ajcn.116.134403 
  43. de Brito, N. J. N., Rocha, É. D., de Araújo Silva, A., Costa, J. B. S., França, M. C., das Graças Almeida, M., & Brandão-Neto, J. (2014). Oral zinc supplementation decreases the serum iron concentration in healthy schoolchildren: A pilot study. Nutrients, 6(9), 3460–3473. https://doi.org/10.3390/nu6093460 
  44. de Carvalho, G. B., Brandão-Lima, P. N., Maia, C. S. C., Barbosa, K. B. F., & Pires, L. V. (2017). Zinc’s role in the glycemic control of patients with type 2 diabetes: A systematic review. Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine, 30(2), 151–162. https://doi.org/10.1007/s10534-017-9996-y 
  45. de Menêses, A. G., Normando, A. G. C., Porto de Toledo, I., Reis, P. E. D., & Guerra, E. N. S. (2020). Effects of oral supplementation in the management of oral mucositis in cancer patients: A meta-analysis of randomized clinical trials. Journal of Oral Pathology & Medicine, 49(2), 117–125. https://doi.org/10.1111/jop.12901 
  46. Dekker, L. H., & Villamor, E. (2010). Zinc supplementation in children is not associated with decreases in hemoglobin concentrations. The Journal of Nutrition, 140(5), 1035–1040. https://doi.org/10.3945/jn.109.119305 
  47. Dhingra, U., Kisenge, R., Sudfeld, C. R., Dhingra, P., Somji, S., Dutta, A., Bakari, M., Deb, S., Devi, P., Liu, E., Chauhan, A., Kumar, J., Semwal, O. P., Aboud, S., Bahl, R., Ashorn, P., Simon, J., Duggan, C. P., Sazawal, S., & Manji, K. (2020). Lower-dose zinc for childhood diarrhea - A randomized, multicenter trial. The New England Journal of Medicine, 383(13), 1231–1241. https://doi.org/10.1056/NEJMoa1915905 
  48. Dissanayake, D., Wijesinghe, P., Ratnasooriya, W., & Wimalasena, S. (2010). Relationship between seminal plasma zinc and semen quality in a subfertile population. Journal of Human Reproductive Sciences, 3(3), 124–128. https://doi.org/10.4103/0974-1208.74153 
  49. Donangelo, C. M., Woodhouse, L. R., King, S. M., Viteri, F. E., & King, J. C. (2002). Supplemental zinc lowers measures of iron status in young women with low iron reserves. The Journal of Nutrition, 132(7), 1860–1864. https://doi.org/10.1093/jn/132.7.1860 
  50. Dreno, B., Amblard, P., Agache, P., Sirot, S., & Litoux, P. (1989). Low doses of zinc gluconate for inflammatory acne. Acta Dermato-Venereologica, 69(6), 541–543. https://www.ncbi.nlm.nih.gov/pubmed/2575335 
  51. Dreno, B., Moyse, D., Alirezai, M., Amblard, P., Auffret, N., Beylot, C., Bodokh, I., Chivot, M., Daniel, F., Humbert, P., Meynadier, J., Poli, F., & Acne Research and Study Group. (2001). Multicenter randomized comparative double-blind controlled clinical trial of the safety and efficacy of zinc gluconate versus minocycline hydrochloride in the treatment of inflammatory acne vulgaris. Dermatology , 203(2), 135–140. https://doi.org/10.1159/000051728 
  52. El Dib, R., Gameiro, O. L. F., Ogata, M. S. P., Módolo, N. S. P., Braz, L. G., Jorge, E. C., do Nascimento, P., Jr, & Beletate, V. (2015). Zinc supplementation for the prevention of type 2 diabetes mellitus in adults with insulin resistance. Cochrane Database of Systematic Reviews, 5, CD005525. https://doi.org/10.1002/14651858.CD005525.pub3 
  53. Ertekin, M. V., Koç, M., Karslioglu, I., & Sezen, O. (2004). Zinc sulfate in the prevention of radiation-induced oropharyngeal mucositis: a prospective, placebo-controlled, randomized study. International Journal of Radiation Oncology, Biology, Physics, 58(1), 167–174. https://doi.org/10.1016/s0360-3016(03)01562-1 
  54. Faghfouri, A. H., Baradaran, B., Khabbazi, A., Khaje Bishak, Y., Zarezadeh, M., Tavakoli-Rouzbehani, O. M., Faghfuri, E., Payahoo, L., Alipour, M., & Alipour, B. (2021). Profiling inflammatory cytokines following zinc supplementation: A systematic review and meta-analysis of controlled trials. The British Journal of Nutrition, 1–10. https://doi.org/10.1017/S0007114521000192 
  55. Farhang, B., & Grondin, L. (2018). The effect of zinc lozenge on postoperative sore throat: a prospective randomized, double-blinded, placebo-controlled study. Anesthesia and Analgesia, 126(1), 78–83. https://doi.org/10.1213/ANE.0000000000002494 
  56. Fernández-Cao, J. C., Warthon-Medina, M., H Moran, V., Arija, V., Doepking, C., Serra-Majem, L., & Lowe, N. M. (2019). Zinc intake and status and risk of type 2 diabetes mellitus: A systematic review and meta-analysis. Nutrients, 11(5). https://doi.org/10.3390/nu11051027 
  57. Festa, M. D., Anderson, H. L., Dowdy, R. P., & Ellersieck, M. R. (1985). Effect of zinc intake on copper excretion and retention in men. The American Journal of Clinical Nutrition, 41(2), 285–292. https://doi.org/10.1093/ajcn/41.2.285 
  58. Foster, M., Chu, A., Petocz, P., & Samman, S. (2013). Effect of vegetarian diets on zinc status: A systematic review and meta-analysis of studies in humans. Journal of the Science of Food and Agriculture, 93(10), 2362–2371. https://doi.org/10.1002/jsfa.6179 
  59. Foster, M., Petocz, P., & Samman, S. (2010). Effects of zinc on plasma lipoprotein cholesterol concentrations in humans: A meta-analysis of randomised controlled trials. Atherosclerosis, 210(2), 344–352. https://doi.org/10.1016/j.atherosclerosis.2009.11.038 
  60. Galvao, T. F., Thees, M. F. R. e. S., Pontes, R. F., Silva, M. T., & Pereira, M. G. (2013). Zinc supplementation for treating diarrhea in children: A systematic review and meta-analysis. Pan American Journal of Public Health, 33(5), 370–377. https://doi.org/10.1590/s1020-49892013000500009 
  61. Gandia, P., Bour, D., Maurette, J.-M., Donazzolo, Y., Duchène, P., Béjot, M., & Houin, G. (2007). A bioavailability study comparing two oral formulations containing zinc (Zn bis-glycinate vs. Zn gluconate) after a single administration to twelve healthy female volunteers. International Journal for Vitamin and Nutrition Research, 77(4), 243–248. https://doi.org/10.1024/0300-9831.77.4.243 
  62. Gebreselassie, S. G., & Gashe, F. E. (2011). A systematic review of effect of prenatal zinc supplementation on birthweight: Meta-analysis of 17 randomized controlled trials. Journal of Health, Population, and Nutrition, 29(2), 134–140. https://www.ncbi.nlm.nih.gov/pubmed/21608422 
  63. Gera, T., Shah, D., & Sachdev, H. S. (2019). Zinc supplementation for promoting growth in children under 5 years of age in low- and middle-income countries: A systematic review. Indian Pediatrics, 56(5), 391–406. https://www.ncbi.nlm.nih.gov/pubmed/30898990 
  64. Ghanizadeh, A., & Berk, M. (2013). Zinc for treating of children and adolescents with attention-deficit hyperactivity disorder: A systematic review of randomized controlled clinical trials. European Journal of Clinical Nutrition, 67(1), 122–124. https://doi.org/10.1038/ejcn.2012.177 
  65. Göransson, K., Lidén, S., & Odsell, L. (1978). Oral zinc in acne vulgaris: A clinical and methodological study. Acta Dermato-Venereologica, 58(5), 443–448. https://doi.org/102340/0001555558443448 
  66. Goudet, S. M., Bogin, B. A., Madise, N. J., & Griffiths, P. L. (2019). Nutritional interventions for preventing stunting in children (birth to 59 months) living in urban slums in low- and middle-income countries (LMIC). Cochrane Database of Systematic Reviews, 6, CD011695. https://doi.org/10.1002/14651858.CD011695.pub2 
  67. Gupta, M., Mahajan, V. K., Mehta, K. S., & Chauhan, P. S. (2014). Zinc therapy in dermatology: A review. Dermatology Research and Practice, 2014, 709152. https://doi.org/10.1155/2014/709152 
  68. Gupta, S., Brazier, A. K. M., & Lowe, N. M. (2020). Zinc deficiency in low- and middle-income countries: Prevalence and approaches for mitigation. Journal of Human Nutrition and Dietetics, 33(5), 624–643. https://doi.org/10.1111/jhn.12791 
  69. Haider, B. A., Lassi, Z. S., Ahmed, A., & Bhutta, Z. A. (2011). Zinc supplementation as an adjunct to antibiotics in the treatment of pneumonia in children 2 to 59 months of age. Cochrane Database of Systematic Reviews, 10, CD007368. https://doi.org/10.1002/14651858.CD007368.pub2 
  70. Hariri, M., & Azadbakht, L. (2015). Magnesium, iron, and zinc supplementation for the treatment of attention deficit hyperactivity disorder: A systematic review on the recent literature. International Journal of Preventive Medicine, 6, 83. https://doi.org/10.4103/2008-7802.164313 
  71. Hashemian, M., Poustchi, H., Mohammadi-Nasrabadi, F., & Hekmatdoost, A. (2015). Systematic review of zinc biochemical indicators and risk of coronary heart disease. ARYA Atherosclerosis, 11(6), 357–365. https://www.ncbi.nlm.nih.gov/pubmed/26862344 
  72. Hemilä, H. (2011). Zinc lozenges may shorten the duration of colds: A systematic review. The Open Respiratory Medicine Journal, 5, 51–58. https://doi.org/10.2174/1874306401105010051 
  73. Hemilä, H., & Chalker, E. (2015). The effectiveness of high dose zinc acetate lozenges on various common cold symptoms: A meta-analysis. BMC Family Practice, 16, 24. https://doi.org/10.1186/s12875-015-0237-6 
  74. Hemilä, H., Petrus, E. J., Fitzgerald, J. T., & Prasad, A. (2016). Zinc acetate lozenges for treating the common cold: An individual patient data meta-analysis. British Journal of Clinical Pharmacology, 82(5), 1393–1398. https://doi.org/10.1111/bcp.13057 
  75. Henderson, L. M., Brewer, G. J., Dressman, J. B., Swidan, S. Z., DuRoss, D. J., Adair, C. H., Barnett, J. L., & Berardi, R. R. (1995). Effect of intragastric pH on the absorption of oral zinc acetate and zinc oxide in young healthy volunteers. Journal of Parenteral and Enteral Nutrition, 19(5), 393–397. https://doi.org/10.1177/0148607195019005393 
  76. Hillström, L., Pettersson, L., Hellbe, L., Kjellin, A., Leczinsky, C. G., & Nordwall, C. (1977). Comparison of oral treatment with zinc sulphate and placebo in acne vulgaris. The British Journal of Dermatology, 97(6), 681–684. https://doi.org/10.1111/j.1365-2133.1977.tb14277.x 
  77. Hoppe, C., Kutschan, S., Dörfler, J., Büntzel, J., Büntzel, J., & Huebner, J. (2021). Zinc as a complementary treatment for cancer patients: A systematic review. Clinical and Experimental Medicine, 21(2), 297–313. https://doi.org/10.1007/s10238-020-00677-6 
  78. Hosseini, R., Ferns, G. A., Sahebkar, A., Mirshekar, M. A., & Jalali, M. (2021). Zinc supplementation is associated with a reduction in serum markers of inflammation and oxidative stress in adults: A systematic review and meta-analysis of randomized controlled trials. Cytokine, 138, 155396. https://doi.org/10.1016/j.cyto.2020.155396 
  79. Iannotti, L. L., Zavaleta, N., León, Z., Shankar, A. H., & Caulfield, L. E. (2008). Maternal zinc supplementation and growth in Peruvian infants. The American Journal of Clinical Nutrition, 88(1), 154–160. https://doi.org/10.1093/ajcn/88.1.154 
  80. Imdad, A., & Bhutta, Z. A. (2011). Effect of preventive zinc supplementation on linear growth in children under 5 years of age in developing countries: A meta-analysis of studies for input to the lives saved tool. BMC Public Health, 11 Suppl 3, S22. https://doi.org/10.1186/1471-2458-11-S3-S22 
  81. Jafari, A., Noormohammadi, Z., Askari, M., & Daneshzad, E. (2020). Zinc supplementation and immune factors in adults: A systematic review and meta-analysis of randomized clinical trials. Critical Reviews in Food Science and Nutrition, 1–19. https://doi.org/10.1080/10408398.2020.1862048 
  82. Jafari, F., Amani, R., & Tarrahi, M. J. (2020). Effect of zinc supplementation on physical and psychological symptoms, biomarkers of inflammation, oxidative stress, and brain-derived neurotrophic factor in young women with premenstrual syndrome: A randomized, double-blind, placebo-controlled trial. Biological Trace Element Research, 194(1), 89–95. https://doi.org/10.1007/s12011-019-01757-9 
  83. Jayawardena, R., Ranasinghe, P., Galappatthy, P., Malkanthi, R., Constantine, G., & Katulanda, P. (2012). Effects of zinc supplementation on diabetes mellitus: A systematic review and meta-analysis. Diabetology & Metabolic Syndrome, 4(1), 13. https://doi.org/10.1186/1758-5996-4-13 
  84. Jiménez-Morán, E., Bacardí-Gascón, M., & Jiménez-Cruz, A. (2013). [Efficacy of zinc on lineal growth on Latin American children younger than 5; systematic review]. Nutricion hospitalaria: organo oficial de la Sociedad Espanola de Nutricion Parenteral y Enteral, 28(5), 1574–1579. https://doi.org/10.3305/nh.2013.28.5.6771 
  85. Kajanachumpol, S., Srisurapanon, S., Supanit, I., Roongpisuthipong, C., & Apibal, S. (1995). Effect of zinc supplementation on zinc status, copper status and cellular immunity in elderly patients with diabetes mellitus. Journal of the Medical Association of Thailand, 78(7), 344–349. https://www.ncbi.nlm.nih.gov/pubmed/7658178 
  86. Karamali, M., Heidarzadeh, Z., Seifati, S. M., Samimi, M., Tabassi, Z., Hajijafari, M., Asemi, Z., & Esmaillzadeh, A. (2015). Zinc supplementation and the effects on metabolic status in gestational diabetes: A randomized, double-blind, placebo-controlled trial. Journal of Diabetes and Its Complications, 29(8), 1314–1319. https://doi.org/10.1016/j.jdiacomp.2015.07.001 
  87. Kewcharoenwong, C., Schuster, G. U., Wessells, K. R., Hinnouho, G.-M., Barffour, M. A., Kounnavong, S., Brown, K. H., Hess, S. Y., Samer, W., Tussakhon, I., Peerson, J. M., Lertmemongkolchai, G., & Stephensen, C. B. (2020). Daily preventive zinc supplementation decreases lymphocyte and eosinophil concentrations in rural laotian children from communities with a high prevalence of zinc deficiency: Results of a randomized controlled trial. The Journal of Nutrition, 150(8), 2204–2213. https://doi.org/10.1093/jn/nxaa037 
  88. Khazdouz, M., Djalalinia, S., Sarrafi Zadeh, S., Hasani, M., Shidfar, F., Ataie-Jafari, A., Asayesh, H., Zarei, M., Gorabi, A. M., Noroozi, M., & Qorbani, M. (2020). Effects of zinc supplementation on cardiometabolic risk factors: A systematic review and meta-analysis of randomized controlled trials. Biological Trace Element Research, 195(2), 373–398. https://doi.org/10.1007/s12011-019-01870-9 
  89. Khazdouz, M., Mazidi, M., Ehsaei, M.-R., Ferns, G., Kengne, A. P., & Norouzy, A.-R. (2018). Impact of zinc supplementation on the clinical outcomes of patients with severe head trauma: A double-blind randomized clinical trial. Journal of Dietary Supplements, 15(1), 1–10. https://doi.org/10.1080/19390211.2017.1304486 
  90. Kim, J., & Ahn, J. (2014). Effect of zinc supplementation on inflammatory markers and adipokines in young obese women. Biological Trace Element Research, 157(2), 101–106. https://doi.org/10.1007/s12011-013-9885-3 
  91. Kurmis, R., Greenwood, J., & Aromataris, E. (2016). Trace element supplementation following severe burn injury: A systematic review and meta-analysis. Journal of Burn Care & Research, 37(3), 143–159. https://doi.org/10.1097/BCR.0000000000000259 
  92. Lai, J., Moxey, A., Nowak, G., Vashum, K., Bailey, K., & McEvoy, M. (2012). The efficacy of zinc supplementation in depression: Systematic review of randomised controlled trials. Journal of Affective Disorders, 136(1-2), e31–e39. https://doi.org/10.1016/j.jad.2011.06.022 
  93. Lamberti, L. M., Walker, C. L. F., Chan, K. Y., Jian, W.-Y., & Black, R. E. (2013). Oral zinc supplementation for the treatment of acute diarrhea in children: A systematic review and meta-analysis. Nutrients, 5(11), 4715–4740. https://doi.org/10.3390/nu5114715 
  94. Lassi, Z. S., Kurji, J., Oliveira, C. S. de, Moin, A., & Bhutta, Z. A. (2020). Zinc supplementation for the promotion of growth and prevention of infections in infants less than six months of age. Cochrane Database of Systematic Reviews, 4, CD010205. https://doi.org/10.1002/14651858.CD010205.pub2 
  95. Lassi, Z. S., Moin, A., & Bhutta, Z. A. (2016). Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months. Cochrane Database of Systematic Reviews, 12, CD005978. https://doi.org/10.1002/14651858.CD005978.pub3 
  96. Lazzerini, M., & Wanzira, H. (2016). Oral zinc for treating diarrhoea in children. Cochrane Database of Systematic Reviews, 12, CD005436. https://doi.org/10.1002/14651858.CD005436.pub5 
  97. Li, Z., Wang, W., Liu, H., Li, S., & Zhang, D. (2019). The association of serum zinc and copper with hypertension: A meta-analysis. Journal of Trace Elements in Medicine and Biology, 53, 41–48. https://doi.org/10.1016/j.jtemb.2019.01.018 
  98. Lin, L.-C., Que, J., Lin, L.-K., & Lin, F.-C. (2006). Zinc supplementation to improve mucositis and dermatitis in patients after radiotherapy for head-and-neck cancers: A double-blind, randomized study. International Journal of Radiation Oncology, Biology, Physics, 65(3), 745–750. https://doi.org/10.1016/j.ijrobp.2006.01.015 
  99. Liu, E., Pimpin, L., Shulkin, M., Kranz, S., Duggan, C. P., Mozaffarian, D., & Fawzi, W. W. (2018). Effect of zinc supplementation on growth outcomes in children under 5 years of age. Nutrients, 10(3). https://doi.org/10.3390/nu10030377 
  100. Lukacik, M., Thomas, R. L., & Aranda, J. V. (2008). A meta-analysis of the effects of oral zinc in the treatment of acute and persistent diarrhea. Pediatrics, 121(2), 326–336. https://doi.org/10.1542/peds.2007-0921 
  101. Ma, Y., Zhang, X., Fan, D., Xia, Q., Wang, M., & Pan, F. (2019). Common trace metals in rheumatoid arthritis: A systematic review and meta-analysis. Journal of Trace Elements in Medicine and Biology, 56, 81–89. https://doi.org/10.1016/j.jtemb.2019.07.007 
  102. Maares, M., & Haase, H. (2020). A guide to human zinc absorption: General overview and recent advances of in vitro intestinal models. Nutrients, 12(3). https://doi.org/10.3390/nu12030762 
  103. Mahmood, A., FitzGerald, A. J., Marchbank, T., Ntatsaki, E., Murray, D., Ghosh, S., & Playford, R. J. (2007). Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes. Gut, 56(2), 168–175. https://doi.org/10.1136/gut.2006.099929 
  104. Maret, W., & Sandstead, H. H. (2006). Zinc requirements and the risks and benefits of zinc supplementation. Journal of Trace Elements in Medicine and Biology, 20(1), 3–18. https://doi.org/10.1016/j.jtemb.2006.01.006 
  105. Mayo-Wilson, E., Junior, J. A., Imdad, A., Dean, S., Chan, X. H. S., Chan, E. S., Jaswal, A., & Bhutta, Z. A. (2014). Zinc supplementation for preventing mortality, morbidity, and growth failure in children aged 6 months to 12 years of age. Cochrane Database of Systematic Reviews, 5, CD009384. https://doi.org/10.1002/14651858.CD009384.pub2 
  106. Merialdi, M., Caulfield, L. E., Zavaleta, N., Figueroa, A., Costigan, K. A., Dominici, F., & Dipietro, J. A. (2004). Randomized controlled trial of prenatal zinc supplementation and fetal bone growth. The American Journal of Clinical Nutrition, 79(5), 826–830. https://doi.org/10.1093/ajcn/79.5.826 
  107. Merialdi, M., Caulfield, L. E., Zavaleta, N., Figueroa, A., Dominici, F., & Dipietro, J. A. (2004). Randomized controlled trial of prenatal zinc supplementation and the development of fetal heart rate. American Journal of Obstetrics and Gynecology, 190(4), 1106–1112. https://doi.org/10.1016/j.ajog.2003.09.072 
  108. Momen-Heravi, M., Barahimi, E., Razzaghi, R., Bahmani, F., Gilasi, H. R., & Asemi, Z. (2017). The effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial. Wound Repair and Regeneration, 25(3), 512–520. https://doi.org/10.1111/wrr.12537 
  109. Mousavi, S. M., Djafarian, K., Mojtahed, A., Varkaneh, H. K., & Shab-Bidar, S. (2018). The effect of zinc supplementation on plasma C-reactive protein concentrations: A systematic review and meta-analysis of randomized controlled trials. European Journal of Pharmacology, 834, 10–16. https://doi.org/10.1016/j.ejphar.2018.07.019 
  110. Mousavi, S. M., Hajishafiee, M., Clark, C. C. T., Borges do Nascimento, I. J., Milajerdi, A., Amini, M. R., & Esmaillzadeh, A. (2020). Clinical effectiveness of zinc supplementation on the biomarkers of oxidative stress: A systematic review and meta-analysis of randomized controlled trials. Pharmacological Research, 161, 105166. https://doi.org/10.1016/j.phrs.2020.105166 
  111. National Institutes of Health. (2021, March 26). Zinc: Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/ 
  112. Nissensohn, M., Sánchez-Villegas, A., Fuentes Lugo, D., Henríquez Sánchez, P., Doreste Alonso, J., Peña Quintana, L., Ruano, C., Lowe, N. L., Hall Moran, V., Skinner, A. L., Warthon-Medina, M., & Serra-Majem, L. (2016). Effect of zinc intake on growth in infants: A meta-analysis. Critical Reviews in Food Science and Nutrition, 56(3), 350–363. https://doi.org/10.1080/10408398.2013.802661 
  113. Nossier, S. A., Naeim, N. E., El-Sayed, N. A., & Abu Zeid, A. A. (2015). The effect of zinc supplementation on pregnancy outcomes: A double-blind, randomised controlled trial, Egypt. The British Journal of Nutrition, 114(2), 274–285. https://doi.org/10.1017/S000711451500166X 
  114. Nowak, G., Siwek, M., Dudek, D., Zieba, A., & Pilc, A. (2003). Effect of zinc supplementation on antidepressant therapy in unipolar depression: A preliminary placebo-controlled study. Polish Journal of Pharmacology, 55(6), 1143–1147. https://www.ncbi.nlm.nih.gov/pubmed/14730113 
  115. O’Connor, S., & Murphy, S. (2014). Chronic venous leg ulcers: Is topical zinc the answer? A review of the literature. Advances in Skin & Wound Care, 27(1), 35–44. https://doi.org/10.1097/01.ASW.0000439173.79541.96 
  116. Olivares, M., Pizarro, F., & Ruz, M. (2007). New insights about iron bioavailability inhibition by zinc. Nutrition, 23(4), 292–295. https://doi.org/10.1016/j.nut.2007.01.006 
  117. Olivares, M., Pizarro, F., Ruz, M., & de Romaña, D. L. (2012). Acute inhibition of iron bioavailability by zinc: Studies in humans. Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine, 25(4), 657–664. https://doi.org/10.1007/s10534-012-9524-z 
  118. Omu, A. E., Al-Azemi, M. K., Kehinde, E. O., Anim, J. T., Oriowo, M. A., & Mathew, T. C. (2008). Indications of the mechanisms involved in improved sperm parameters by zinc therapy. Medical Principles and Practice, 17(2), 108–116. https://doi.org/10.1159/000112963 
  119. Omu, A. E., Dashti, H., & Al-Othman, S. (1998). Treatment of asthenozoospermia with zinc sulphate: Andrological, immunological and obstetric outcome. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 79(2), 179–184. https://doi.org/10.1016/s0301-2115(97)00262-5 
  120. Osendarp, S. J., van Raaij, J. M., Darmstadt, G. L., Baqui, A. H., Hautvast, J. G., & Fuchs, G. J. (2001). Zinc supplementation during pregnancy and effects on growth and morbidity in low birthweight infants: A randomised placebo controlled trial. The Lancet, 357(9262), 1080–1085. https://doi.org/10.1016/s0140-6736(00)04260-4 
  121. Ota, E., Mori, R., Middleton, P., Tobe-Gai, R., Mahomed, K., Miyazaki, C., & Bhutta, Z. A. (2015). Zinc supplementation for improving pregnancy and infant outcome. Cochrane Database of Systematic Reviews, 2, CD000230. https://doi.org/10.1002/14651858.CD000230.pub5 
  122. Patel, A. B., Mamtani, M., Badhoniya, N., & Kulkarni, H. (2011). What zinc supplementation does and does not achieve in diarrhea prevention: A systematic review and meta-analysis. BMC Infectious Diseases, 11, 122. https://doi.org/10.1186/1471-2334-11-122 
  123. Patel, A., Mamtani, M., Dibley, M. J., Badhoniya, N., & Kulkarni, H. (2010). Therapeutic value of zinc supplementation in acute and persistent diarrhea: A systematic review. PloS One, 5(4), e10386. https://doi.org/10.1371/journal.pone.0010386 
  124. Pompano, L. M., & Boy, E. (2021). Effects of dose and duration of zinc interventions on risk factors for type 2 diabetes and cardiovascular disease: A systematic review and meta-analysis. Advances in Nutrition, 12(1), 141–160. https://doi.org/10.1093/advances/nmaa087 
  125. Pories, W. J., Henzel, J. H., Rob, C. G., & Strain, W. H. (1967). Acceleration of wound healing in man with zinc sulphate given by mouth. The Lancet, 1(7482), 121–124. https://doi.org/10.1016/s0140-6736(67)91031-8 
  126. Prasad, A. S., Beck, F. W. J., Bao, B., Fitzgerald, J. T., Snell, D. C., Steinberg, J. D., & Cardozo, L. J. (2007). Zinc supplementation decreases incidence of infections in the elderly: Effect of zinc on generation of cytokines and oxidative stress. The American Journal of Clinical Nutrition, 85(3), 837–844. https://doi.org/10.1093/ajcn/85.3.837 
  127. Rambod, M., Pasyar, N., & Ramzi, M. (2018). The effect of zinc sulfate on prevention, incidence, and severity of mucositis in leukemia patients undergoing chemotherapy. European Journal of Oncology Nursing, 33, 14–21. https://doi.org/10.1016/j.ejon.2018.01.007 
  128. Ranasinghe, P., Wathurapatha, W. S., Ishara, M. H., Jayawardana, R., Galappatthy, P., Katulanda, P., & Constantine, G. R. (2015). Effects of zinc supplementation on serum lipids: A systematic review and meta-analysis. Nutrition & Metabolism, 12, 26. https://doi.org/10.1186/s12986-015-0023-4 
  129. Ranjbar, E., Shams, J., Sabetkasaei, M., M-Shirazi, M., Rashidkhani, B., Mostafavi, A., Bornak, E., & Nasrollahzadeh, J. (2014). Effects of zinc supplementation on efficacy of antidepressant therapy, inflammatory cytokines, and brain-derived neurotrophic factor in patients with major depression. Nutritional Neuroscience, 17(2), 65–71. https://doi.org/10.1179/1476830513Y.0000000066 
  130. Roberts, J. L., & Stein, A. D. (2017). The impact of nutritional interventions beyond the first 2 years of life on linear growth: A systematic review and meta-analysis. Advances in Nutrition, 8(2), 323–336. https://doi.org/10.3945/an.116.013938 
  131. Roohani, N., Hurrell, R., Kelishadi, R., & Schulin, R. (2013). Zinc and its importance for human health: An integrative review. Journal of Research in Medical Sciences, 18(2), 144–157. https://www.ncbi.nlm.nih.gov/pubmed/23914218 
  132. Rosado, J. L., Muñoz, E., López, P., & Allen, L. H. (1993). Absorption of zinc sulfate, methionine, and polyascorbate in the presence and absence of a plant-based rural mexican diet. Nutrition Research , 13(10), 1141–1151. https://doi.org/10.1016/S0271-5317(05)80738-9 
  133. Roth, D. E., Richard, S. A., & Black, R. E. (2010). Zinc supplementation for the prevention of acute lower respiratory infection in children in developing countries: Meta-analysis and meta-regression of randomized trials. International Journal of Epidemiology, 39(3), 795–808. https://doi.org/10.1093/ije/dyp391 
  134. Saghazadeh, A., Mahmoudi, M., Shahrokhi, S., Mojarrad, M., Dastmardi, M., Mirbeyk, M., & Rezaei, N. (2020). Trace elements in schizophrenia: A systematic review and meta-analysis of 39 studies (N = 5151 participants). Nutrition Reviews, 78(4), 278–303. https://doi.org/10.1093/nutrit/nuz059 
  135. Salari, S., Khomand, P., Arasteh, M., Yousefzamani, B., & Hassanzadeh, K. (2015). Zinc sulphate: A reasonable choice for depression management in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled clinical trial. Pharmacological Reports, 67(3), 606–609. https://doi.org/10.1016/j.pharep.2015.01.002 
  136. Salas-Huetos, A., Rosique-Esteban, N., Becerra-Tomás, N., Vizmanos, B., Bulló, M., & Salas-Salvadó, J. (2018). The effect of nutrients and dietary supplements on sperm quality parameters: A systematic review and meta-analysis of randomized clinical trials. Advances in Nutrition, 9(6), 833–848. https://doi.org/10.1093/advances/nmy057 
  137. Sanna, A., Firinu, D., Zavattari, P., & Valera, P. (2018). Zinc status and autoimmunity: A systematic review and meta-analysis. Nutrients, 10(1). https://doi.org/10.3390/nu10010068 
  138. Santos, H. O., & Teixeira, F. J. (2020). Use of medicinal doses of zinc as a safe and efficient coadjutant in the treatment of male hypogonadism. The Aging Male, 23(5), 669–678. https://doi.org/10.1080/13685538.2019.1573220 
  139. Santos, H. O., Teixeira, F. J., & Schoenfeld, B. J. (2020). Dietary vs. pharmacological doses of zinc: A clinical review. Clinical Nutrition, 39(5), 1345–1353. https://doi.org/10.1016/j.clnu.2019.06.024 
  140. Sazawal, S., Jalla, S., Mazumder, S., Sinha, A., Black, R. E., & Bhan, M. K. (1997). Effect of zinc supplementation on cell-mediated immunity and lymphocyte subsets in preschool children. Indian Pediatrics, 34(7), 589–597. https://www.ncbi.nlm.nih.gov/pubmed/9401251 
  141. Sazawal, S., Malik, P., Jalla, S., Krebs, N., Bhan, M. K., & Black, R. E. (2004). Zinc supplementation for four months does not affect plasma copper concentration in infants. Acta Paediatrica, 93(5), 599–602. https://doi.org/10.1111/j.1651-2227.2004.tb18254.x 
  142. Schefft, C., Kilarski, L. L., Bschor, T., & Köhler, S. (2017). Efficacy of adding nutritional supplements in unipolar depression: A systematic review and meta-analysis. European Neuropsychopharmacology, 27(11), 1090–1109. https://doi.org/10.1016/j.euroneuro.2017.07.004 
  143. Science, M., Johnstone, J., Roth, D. E., Guyatt, G., & Loeb, M. (2012). Zinc for the treatment of the common cold: A systematic review and meta-analysis of randomized controlled trials. Canadian Medical Association Journal, 184(10), E551–E561. https://doi.org/10.1503/cmaj.111990 
  144. Sharif, R., Thomas, P., Zalewski, P., & Fenech, M. (2015). Zinc supplementation influences genomic stability biomarkers, antioxidant activity, and zinc transporter genes in an elderly Australian population with low zinc status. Molecular Nutrition & Food Research, 59(6), 1200–1212. https://doi.org/10.1002/mnfr.201400784 
  145. Shuai, T., Tian, X., Shi, B., Chen, H., Liu, X.-L., Yi, L.-J., Chen, W.-Q., & Li, X.-E. (2019). Prophylaxis with oral zinc sulfate against radiation induced oral mucositis in patients with head and neck cancers: A systematic review and meta-analysis of four randomized controlled trials. Frontiers in Oncology, 9, 165. https://doi.org/10.3389/fonc.2019.00165 
  146. Siepmann, M., Spank, S., Kluge, A., Schappach, A., & Kirch, W. (2005). The pharmacokinetics of zinc from zinc gluconate: A comparison with zinc oxide in healthy men. International Journal of Clinical Pharmacology and Therapeutics, 43(12), 562–565. https://doi.org/10.5414/cpp43562 
  147. Singh, M., & Das, R. R. (2015). Zinc for the common cold. Cochrane Database of Systematic Reviews, 4, CD001364. https://doi.org/10.1002/14651858.CD001364.pub5 
  148. Siwek, M., Dudek, D., Paul, I. A., Sowa-Kućma, M., Zieba, A., Popik, P., Pilc, A., & Nowak, G. (2009). Zinc supplementation augments efficacy of imipramine in treatment resistant patients: A double blind, placebo-controlled study. Journal of Affective Disorders, 118(1-3), 187–195. https://doi.org/10.1016/j.jad.2009.02.014 
  149. Solati, Z., Jazayeri, S., Tehrani-Doost, M., Mahmoodianfard, S., & Gohari, M. R. (2015). Zinc monotherapy increases serum brain-derived neurotrophic factor (BDNF) levels and decreases depressive symptoms in overweight or obese subjects: A double-blind, randomized, placebo-controlled trial. Nutritional Neuroscience, 18(4), 162–168. https://doi.org/10.1179/1476830513Y.0000000105 
  150. Song, Y.-P., Wang, L., Yu, H.-R., Yuan, B.-F., Shen, H.-W., Du, L., Cai, J.-Y., & Chen, H.-L. (2020). Zinc therapy is a reasonable choice for patients with pressure injuries: A systematic review and meta-analysis. Nutrition in Clinical Practice, 35(6), 1001–1009. https://doi.org/10.1002/ncp.10485 
  151. Stammers, A. L., Lowe, N. M., Medina, M. W., Patel, S., Dykes, F., Pérez-Rodrigo, C., Serra-Majam, L., Nissensohn, M., & Moran, V. H. (2015). The relationship between zinc intake and growth in children aged 1-8 years: A systematic review and meta-analysis. European Journal of Clinical Nutrition, 69(2), 147–153. https://doi.org/10.1038/ejcn.2014.204 
  152. Sun, H., Liu, X., Ge, H., Wang, T., Wang, Y., & Li, W. (2017). Association between serum zinc levels and the risk of Parkinson’s disease: A meta-analysis. Biological Trace Element Research, 179(1), 45–51. https://doi.org/10.1007/s12011-017-0941-2 
  153. Talebi, S., Ghaedi, E., Sadeghi, E., Mohammadi, H., Hadi, A., Clark, C. C. T., & Askari, G. (2020). Trace element status and hypothyroidism: A systematic review and meta-analysis. Biological Trace Element Research, 197(1), 1–14. https://doi.org/10.1007/s12011-019-01963-5 
  154. Tie, H.-T., Tan, Q., Luo, M.-Z., Li, Q., Yu, J.-L., & Wu, Q.-C. (2016). Zinc as an adjunct to antibiotics for the treatment of severe pneumonia in children <5 years: A meta-analysis of randomised-controlled trials. The British Journal of Nutrition, 115(5), 807–816. https://doi.org/10.1017/S0007114515005449 
  155. Ventriglia, M., Brewer, G. J., Simonelli, I., Mariani, S., Siotto, M., Bucossi, S., & Squitti, R. (2015). Zinc in Alzheimer's disease: A meta-analysis of serum, plasma, and cerebrospinal fluid studies. Journal of Alzheimer’s Disease, 46(1), 75–87. https://doi.org/10.3233/JAD-141296 
  156. Verma, K. C., Saini, A. S., & Dhamija, S. K. (1980). Oral zinc sulphate therapy in acne vulgaris: A double-blind trial. Acta Dermato-Venereologica, 60(4), 337–340. https://doi.org/10.2340/0001555560337340 
  157. Walker, C. L. F., & Black, R. E. (2010). Zinc for the treatment of diarrhoea: Effect on diarrhoea morbidity, mortality and incidence of future episodes. International Journal of Epidemiology, 39 Suppl 1, i63–i69. https://doi.org/10.1093/ije/dyq023 
  158. Wang, L., & Song, Y. (2018). Efficacy of zinc given as an adjunct to the treatment of severe pneumonia: A meta-analysis of randomized, double-blind and placebo-controlled trials. The Clinical Respiratory Journal, 12(3), 857–864. https://doi.org/10.1111/crj.12646 
  159. Wang, L.-J., Wang, M.-Q., Hu, R., Yang, Y., Huang, Y.-S., Xian, S.-X., & Lu, L. (2017). Effect of zinc supplementation on maintenance hemodialysis patients: A systematic review and meta-analysis of 15 randomized controlled trials. BioMed Research International, 2017, 1024769. https://doi.org/10.1155/2017/1024769 
  160. Wang, M. X., Win, S. S., & Pang, J. (2020). Zinc supplementation reduces common cold duration among healthy adults: A systematic review of randomized controlled trials with micronutrients supplementation. The American Journal of Tropical Medicine and Hygiene, 103(1), 86–99. https://doi.org/10.4269/ajtmh.19-0718 
  161. Wang, X., Wu, W., Zheng, W., Fang, X., Chen, L., Rink, L., Min, J., & Wang, F. (2019). Zinc supplementation improves glycemic control for diabetes prevention and management: A systematic review and meta-analysis of randomized controlled trials. The American Journal of Clinical Nutrition, 110(1), 76–90. https://doi.org/10.1093/ajcn/nqz041 
  162. Watari, I., Oka, S., Tanaka, S., Aoyama, T., Imagawa, H., Shishido, T., Yoshida, S., & Chayama, K. (2013). Effectiveness of polaprezinc for low-dose aspirin-induced small-bowel mucosal injuries as evaluated by capsule endoscopy: A pilot randomized controlled study. BMC Gastroenterology, 13, 108. https://doi.org/10.1186/1471-230X-13-108 
  163. Wegmüller, R., Tay, F., Zeder, C., Brnic, M., & Hurrell, R. F. (2014). Zinc absorption by young adults from supplemental zinc citrate is comparable with that from zinc gluconate and higher than from zinc oxide. The Journal of Nutrition, 144(2), 132–136. https://doi.org/10.3945/jn.113.181487 
  164. Wiggelinkhuizen, M., Tilanus, M. E. C., Bollen, C. W., & Houwen, R. H. J. (2009). Systematic review: Clinical efficacy of chelator agents and zinc in the initial treatment of Wilson disease. Alimentary Pharmacology & Therapeutics, 29(9), 947–958. https://doi.org/10.1111/j.1365-2036.2009.03959.x 
  165. Wilkinson, E. A. J. (2014). Oral zinc for arterial and venous leg ulcers. Cochrane Database of Systematic Reviews, 9, CD001273. https://doi.org/10.1002/14651858.CD001273.pub3 
  166. Willis, M. S., Monaghan, S. A., Miller, M. L., McKenna, R. W., Perkins, W. D., Levinson, B. S., Bhushan, V., & Kroft, S. H. (2005). Zinc-induced copper deficiency: A report of three cases initially recognized on bone marrow examination. American Journal of Clinical Pathology, 123(1), 125–131. https://doi.org/10.1309/v6gvyw2qtyd5c5pj 
  167. Wolfe, S. A., Gibson, R. S., Gadowsky, S. L., & O’Connor, D. L. (1994). Zinc status of a group of pregnant adolescents at 36 weeks gestation living in southern Ontario. Journal of the American College of Nutrition, 13(2), 154–164. https://doi.org/10.1080/07315724.1994.10718389 
  168. Wong, W. Y., Merkus, H. M. W. M., Thomas, C. M. G., Menkveld, R., Zielhuis, G. A., & Steegers-Theunissen, R. P. M. (2002). Effects of folic acid and zinc sulfate on male factor subfertility: A double-blind, randomized, placebo-controlled trial. Fertility and Sterility, 77(3), 491–498. https://doi.org/10.1016/s0015-0282(01)03229-0 
  169. Wuehler, S. E., Sempértegui, F., & Brown, K. H. (2008). Dose-response trial of prophylactic zinc supplements, with or without copper, in young Ecuadorian children at risk of zinc deficiency. The American Journal of Clinical Nutrition, 87(3), 723–733. https://doi.org/10.1093/ajcn/87.3.723 
  170. Yakoob, M. Y., Theodoratou, E., Jabeen, A., Imdad, A., Eisele, T. P., Ferguson, J., Jhass, A., Rudan, I., Campbell, H., Black, R. E., & Bhutta, Z. A. (2011). Preventive zinc supplementation in developing countries: Impact on mortality and morbidity due to diarrhea, pneumonia and malaria. BMC Public Health, 11 Suppl 3, S23. https://doi.org/10.1186/1471-2458-11-S3-S23 
  171. Yee, B. E., Richards, P., Sui, J. Y., & Marsch, A. F. (2020). Serum zinc levels and efficacy of zinc treatment in acne vulgaris: A systematic review and meta-analysis. Dermatologic Therapy, 33(6), e14252. https://doi.org/10.1111/dth.14252 
  172. Yosaee, S., Clark, C. C. T., Keshtkaran, Z., Ashourpour, M., Keshani, P., & Soltani, S. (2020). Zinc in depression: From development to treatment: A comparative/ dose response meta-analysis of observational studies and randomized controlled trials. General Hospital Psychiatry. https://doi.org/10.1016/j.genhosppsych.2020.08.001 
  173. Yosaee, S., Soltani, S., Esteghamati, A., Motevalian, S. A., Tehrani-Doost, M., Clark, C. C. T., & Jazayeri, S. (2020). Effects of zinc, vitamin D, and their co-supplementation on mood, serum cortisol, and brain-derived neurotrophic factor in patients with obesity and mild to moderate depressive symptoms: A phase II, 12-wk, 2 × 2 factorial design, double-blind, randomized, placebo-controlled trial. Nutrition, 71, 110601. https://doi.org/10.1016/j.nut.2019.110601 
  174. Young, B., Ott, L., Kasarskis, E., Rapp, R., Moles, K., Dempsey, R. J., Tibbs, P. A., Kryscio, R., & McClain, C. (1996). Zinc supplementation is associated with improved neurologic recovery rate and visceral protein levels of patients with severe closed head injury. Journal of Neurotrauma, 13(1), 25–34. https://doi.org/10.1089/neu.1996.13.25
  175. Yu, X., Huang, L., Zhao, J., Wang, Z., Yao, W., Wu, X., Huang, J., & Bian, B. (2018). The relationship between serum zinc level and heart failure: A meta-analysis. BioMed Research International, 2018, 2739014. https://doi.org/10.1155/2018/2739014
  176. Zhao, J., Dong, X., Hu, X., Long, Z., Wang, L., Liu, Q., Sun, B., Wang, Q., Wu, Q., & Li, L. (2016). Zinc levels in seminal plasma and their correlation with male infertility: A systematic review and meta-analysis. Scientific Reports, 6, 22386. https://doi.org/10.1038/srep22386
  177. Zou, T.-T., Mou, J., & Zhan, X. (2015). Zinc supplementation in acute diarrhea. Indian Journal of Pediatrics, 82(5), 415–420. https://doi.org/10.1007/s12098-014-1504-6

Get more resources for your practice

Blog
Protocols
Practice resources
Webinars
Back to top
Back to ingredient library

The healthiest cookies you’ll choose today

Our website uses cookies to collect useful information that lets us and our partners support basic functionality, analyze visitor traffic, deliver a better user experience, and provide ads tailored to your interests. Agreeing to the use of cookies is your choice. Learn more