Potencial profilático e terapêutico da suplementação de zinco na incidência de distúrbios do paladar e mucosite durante a quimioterapia: revisão sistemática

Michele Beatriz Konzen; Tatiane da Silva Dal Pizzol; Juliana Ebling Brondani; Liziane Maahs  Flores

doi:10.59171/nutrivisa-2024v11e13012

Authors

Michele Beatriz Konzen Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brasil https://orcid.org/0000-0003-2435-2943
Tatiane da Silva Dal Pizzol Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brasil https://orcid.org/0000-0002-7566-7745
Juliana Ebling Brondani Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG), Belo Horizonte, Minas Gerais, Brasil https://orcid.org/0000-0001-5478-6633
Liziane Maahs Flores Universidade Federal de Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brasil. https://orcid.org/0000-0003-2110-2471

DOI:

https://doi.org/10.59171/nutrivisa-2024v11e13012

Keywords:

zinc sulfate; mucositis; dysgeusia; chemotherapy; systematic review

Abstract

Chemotherapy can cause adverse effects such as mucositis and taste disorders, which tend to reduce daily nutrient intake, contributing to a decline in nutritional status, worse quality of life and risk of treatment interruptions. Zinc supplementation has been considered as an option for the prophylaxis and treatment of these conditions. Therefore, this review aims to summarize the available evidence on the prophylactic and therapeutic use of zinc supplementation in mucositis and taste disorders in patients undergoing chemotherapy. Systematic Review of Randomized Clinical Trials considering mucositis and taste disorders as outcomes. The articles were searched in electronic databases: MEDLINE, EMBASE, Cochrane, VHL, Web of Science and in the references of the articles found. Selection, data extraction and assessment of methodological quality were carried out independently by two reviewers. The risk of bias assessment was carried out using the RoB 2 tool. Of a total of 322 studies retrieved in the searches, 3 were eligible. The studies were heterogeneous in relation to participants, intervention (dosage) and outcome assessment measures. Only one study confirmed the hypothesis that zinc supplementation prevents the incidence of mucositis (p<0.05). However, this was the only one among the eligible studies assessed as having a low risk of bias in terms of methodological quality. Although there is a tendency for zinc sulfate to reduce the incidence and/or severity of mucositis, there is insufficient evidence regarding its effectiveness.

References

ARBABI-KALATI, F.; ARBABI-KALATI, F.; DEGHATIPOUR, M.; MOGHADAM, A. A. Evaluation of the efficacy of zinc sulfate in the prevention of chemotherapy-induced mucositis: a double-blind randomized clinical trial. Arch Iran Med. v.15, n.7, p.413-7, 2012.

ARENDS, J.; BARACOS, V.; BERTZ, H.; BOZZETTI, F.; CALDER, P.C.; DEUTZ, N.E.P.; ERICKSON, N.; LAVIANO.; DEPUTADO LISANTI.; LOBO, D.N.; MCMILLAN, D.C.; MUSCARITOLI, M.; OCKENGA, J.; PIRLICH, M.; STRASSER, F.; DE VAN DER SCHUEREN.; VAN GOSSUM.; VAUPEL, P.; WEIMANN, U.N. ESPEN expert group recommendations for action against cancer-related malnutrition. Clin Nutr. v.36, p.1.187-96, 2017. doi: https://doi.org/10.1016/j.clnu.2017.06.017

ATTAR, T. Levels of serum copper and zinc in healthy adults from the west of Algeria. SPC Journal of Environmental Sciences. v.1, p.26-28, 2019. doi: https://doi.org/10.1016/j.mad.2015.01.004

CRUZ, J.B.F.; SOARES, H.F. Uma revisão sobre o zinco. Ensaios e Ciência C Biológicas Agrárias e da Saúde. v.15, n.1, p.207-222, 2011.

CRUZ-JENTOFT, A.J.; BAHAT, G.; BAUER, J.; BOIRIE, Y.; BRUYÈRE, O.; CEDERHOLM, T.; COOPER, C.; LANDI, F.; ROLLAND, Y.; AIHIE SAYER, A.; SCHNEIDER, S.M.; SIEBER, C.C.; TOPINKOVA, E.; VANDEWOUDE, M.; VISSER, M.; ZAMBONI, M. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. v.48, n.1, p.16-31, 2019. doi: https://doi.org/10.1093/ageing/afy169

CURRA, M.; SOARES JUNIOR, L.A.V.; MARTINS, M.D.; SANTOS, P.S.S. Protocolos quimioterápicos e incidência de mucosite bucal. Revisão integrativa. Einstein. v.16, n.1, p.eRW4007, 2018. doi: http://dx.doi.org/10.1590/S1679-45082018RW4007

GHOLIZADEH, N.; MEHDIPOUR, M.; CHAVOSHI, S.H.; KAHANI, D.; SADRZADEH-AFSHAR, M. The Effect of Orally-Administered Zinc in the Prevention of Chemotherapy-Induced Oral Mucositis in Patients with Acute Myeloid Leukemia. Int J Cancer Manag. v.10, n.8, p.e9252, 2017. doi: https://doi.org/10.5812/ijcm.9252

GHOLIZADEH, N.; SHEYKHBAHAEI, N.; SADRZADEH-AFSHAR, M.S. Novas abordagens de tratamento da mucosite oral: uma revisão da literatura. Adv Hum Biol. v.6, p.66–72, 2016. doi: https://doi.org/10.4103/2321-8568.190319

GRATTAN, B.J.; FREAKE, H.C. Zinc and Cancer: Implications for LIV-1 in Breast Cancer. Nutrients. v.4, n.7, p.648–675, 2012. doi: https://doi.org/10.3390/nu4070648

HOPPE, C.; KUTSCHAN, S.; DÖRFLER, J.; BUNTZEL, J.; BUNTZEL, J.; HUEBNER, J. Zinc as a complementary treatment for cancer patients: a systematic review. Clin Exp Med. v.21, n.2, p.297- 313, 2021. doi: https://doi.org/10.1007/s10238-020-00677-6

HOSUI, A.; KIMURA, E.; ABE, S.; TANIMOTO, T.; ONISHI, T.; KUSUMOTO, Y.; SUEYOSHI, Y.; MATSUMOTO, K.; HIRAO, M.; YAMADA, T.; HIRAMATSU, N. Long-Term Zinc Supplementation Improves Liver Function and Decreases the Risk of Developing Hepatocellular Carcinoma. Nutrients. v.10, n.12, p.1955, 2018. doi https://doi.org/10.3390/nu10121955

JESUS, L.G.; CICCHELLI, M.; MARTINS, G.B.; PEREIRA, M.C.C.; LIMA, H.S.; MEDRADO, A.R.A.P. Repercussões orais de drogas antineoplásicas: uma revisão de literatura. RFO UPF. v.21, n.1, 2016. doi: http://dx.doi.org/10.5335/rfo.v21i1.5052

KODAMA, H.; TANAKA, M.; NAITO, Y.; KATAYAMA, K.; MORIYAMA, M. Japan's Practical Guidelines for Zinc Deficiency with a Particular Focus on Taste Disorders, Inflammatory Bowel Disease, and Liver Cirrhosis. Int J Mol Sci. v.21, n.8, p.2941, 2020. doi: https://doi.org/10.3390%2Fijms21082941

MARDAS, M.; MADRY, R.; MARDAS, M. Dietary intake variability in the cycle of cytotoxic chemotherapy. Support Care Cancer. v.24, p.2619-2625, 2016. doi: https://doi.org/10.1007/s00520-015-3072-3

MARÍN CARO, M.M.; CANDELA, C.G.; RABANEDA, R.; NOGUEIRA, T.L.; HUERTA, M.G.; KOHEN, L.; SANZ, M.V.; AUÑÓN, P.Z.; PÉREZ, L.; SÁENZ, P.R.; LÓPEZ-PORTABELLA, C.; MONZÓN, A.Z.; ROJAS, J.E.; BOQUERAS, R.N.; SUÁREZ, L.R.; PÉREZ, C.; MASFERRER, J.P. Nutritional risk evaluation and establishment of nutritional support in oncology patients according to the protocol of the Spanish Nutrition and Cancer Group. Nutrición Hospitalaria. v.23, n.5, p.458-468, 2008.

MARTINEZ, J.M.; PEREIRA, D.; CHACIM, S.; MESQUITA, E.; SOUSA, I.; MARTINS, A.; AZEVEDO, T.; MARIZ, J.M. Care of mucositis in patients with acute leukemia and non-Hodgkin's lymphoma undergoing high-dose chemotherapy. Support Care Cancer. v.22, p.2563–9, 2014. doi: https://doi.org/10.1007/s00520-014-2199-y

MEHDIPOUR, M.; THAGUAVI ZENOZ, A.; KERMANI, A.; HOSSEINPOUR, A. A comparison between zinc sulfate and chlorhexidine gluconate mouthwashes in the prevention of chemotherapy-induced oral mucositis. Daru. v.19, n.1, p.71–3, 2011.

NINSONTIA, C.; PHIBOONCHAIYANAN, P.P.; KIRATIPAIBOON, C.; CHANVORACHOTE, P. Zinc suppresses stem cell properties of lung cancer cells through protein kinase C-mediated beta-catenin degradation. Am. J. Physiol. Cell Physiol. v.312, n.4, p.C487–C499, 2017. doi: https://doi.org/10.1152/ajpcell.00173.2016

PAGE, M.J.; MCKENZIE, J.E.; BOSSUYT, P.M.; BOUTRON, I.; HOFFMANN, T.C.; MULROW, C.D.; SHAMSEER, L.; TETZLAFF, J.M.; AKL, E.A.; BRENNAN, S.E.; CHOU, R.; GLANVILLE, J.; GRIMSHAW, J.M.; HRÓBJARTSSON, A.; LALU, M.M.; LI, T.; LODER, E.W.; MAYO-WILSON, E.; MCDONALD, S.; MCGUINNESS, L.A.; STEWART, L.A.; THOMAS, T.; TRICCO, A.C.; WELCH, V.A.; WHITING, P.; MOHER, D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. n.71, p.372, 2021. doi: https://doi.org/10.1136/bmj.n71

PAN, Z.; CHOI, S.; OUADID-AHIDOUCH, H.; YANG, J.M.; BEATTIE, J.H.; KORICHNEVA, I. Zinc transporters and dysregulated channels in cancers. Front. Biosci, v. 22, n. 4, p. 623–643, 2017. doi: https://doi.org/10.2741/4507OUZZANI, M.; HAMMADY, H.; FEDOROWICZ, Z.; ELMAGARMID, A. Rayyan—a web and mobile app for systematic reviews. Systematic Reviews. v.5, p.210, 2016. Doi: https://doi.org/10.1186/s13643-016-0384-4

PETERSON, D.; BENSADOUN, R.; ROILA, F. Management of oral and gastrointestinal mucositis: ESMO Clinical Practice Guidelines. Ann Oncol. v.22, n.6, p.78–84, 2011. doi: https://doi.org/10.1093/annonc/mdr391

PRASAD, A.S.; BAO, B. Molecular mechanisms of zinc as a proantioxidant mediator: clinical therapeutic implications. Antioxidants. v.8, n.6, 2019. doi: https://doi.org/10.3390/antiox8060164

RAMBOD, M.; PASYAR, N.; RAMZI, M. The effect of zinc sulfate on prevention, incidence, and severity of mucositis in leukemia patients undergoing chemotherapy. Eur J Oncol Nurs. v.33, p.14-21, 2018. doi: https://doi.org/10.1016/j.ejon.2018.01.007

ROAYAEI, M.; ANDALIB, Z.; AKHAVAN, A. The effect of oral zinc sulfate on prevention of chemotherapy-induced oral mucositis in breast cancer patients treated with adriamycin and cyclophosphamide; a double-blind randomized clinical trial. J Nephropharmacol. v.12, n.1, p.e10533, 2023. doi: https://doi.org/10.34172/npj.2022.10533

RODRÍGUEZ CABALLERO, A.; TORRES-LAGARES, D.; ROBLES-GARCÍA, M.; PACHÓN-IBÁÑEZ, J.; GONZÁLEZ-PADILLA, D.; GUTIÉRREZ-PÉREZ, J.L. Cancer treatment-induced oral mucositis: a critical review. Int J Oral Maxillofac Surg. v.41, p.225–38, 2012. doi: https://doi.org/10.1016/j.ijom.2011.10.011

SANTOS, C.; FONSECA, J. Zinco: fisiopatologia, clínica e nutrição. APNEP v.6, n.1, 2012.

SANTOS, H.O.; TEIXEIRA, F.J.; SCHOENFELD, B.J. Dietary vs. pharmacological doses of zinc: a clinical review. Clinic Nut. v.39, p.1345–53, 2020. doi: https://doi.org/10.1016/j.clnu.2019.06.024

SPIJKERVET, F.K.; SAENE, H.K.V.; PANDERS, A.K.; VERMEY,A.; MEHTA,D.M. Scoring irradiation mucositis in head and neck cancer patients. J Oral Pathol Med. v.18, p.170, 1989. doi: https://doi.org/10.1111/j.1600-0714.1989.tb00756.x

STERNE, J.A.C.; SAVOVIC, J.; PAGE, M.J.; ELBERS, R.G.; BLENCOWE, N.S.; BOUTRON, I.; CATES, C.J.; CHENG, H.; CORBETT, M.S.; ELDRIDGE, S.M.; EMBERSON, J.R.; HERNAN, M.A.; HOPEWELL, S.; HRÓBJARTSSON, A.; JUNQUEIRA, D.R.; JUNI, P.; KIRKHAM, J.J.; LASSERSON, T., LI, T.; MCALEENAN, A.; REEVES, B.C.; SHEPPERD, S.; SHRIER, I.; STEWART, L.A.; TILLING, K.; BRANCO, I.R.; WHITING, P.F.; HIGGINS, J.P.T. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. v.366, p.l4898, 2019. doi: https://doi.org/10.1136/bmj.l4898

TAKATANI-NAKASE, T. Zinc Transporters and the Progression of Breast Cancers. Biol. Pharm. Bull. v.41, p.1517–1522, 2018. doi https://doi.org/10.1248/bpb.b18-00086

TIAN, X.; LIU, X.L.; PI, Y.; CHEN, H.; CHEN, W.Q. Oral Zinc Sulfate for Prevention and Treatment of Chemotherapy[1]Induced Oral Mucositis: A Meta-Analysis of Five Randomized Controlled Trials. Front. Oncol. v.8, p.484, 2018. doi: https://doi.org/10.3389%2Ffonc.2019.00165

WANG, Y.; SUN, Z.; LI, A.; ZHANG, Y. Association between serum zinc levels and lung cancer: a meta-analysis of observational studies. World Journal of Surgical Oncology. v.17, n.78, 2019. doi: https://doi.org/10.1186/s12957-019-1617-5

WORLD HEALTH ORGANIZATION - WHO. Handbook for reporting results of cancer treatment. Geneva: World Health Organization. 1979. Acesso em: 13 de junho de 2023. Disponível em: https://apps.who.int/iris/handle/10665/37200.

YU, Z.; YU, Z.; CHEN, Z.B.; YANG, L.; JUN MA, M.; NAN LU, S.; WANG, C.S.; BO TENG, C.; NIE, Y.Z. Zinc chelator TPEN induces pancreatic cancer cell death through causing oxidative stress and inhibiting cell autophagy. J. Cell. Physiol. v.234, p.20648–661, 2019. doi: https://doi.org/10.1002/jcp.28670

ZILIOTTO, S.; OGLE, O.; TAYLOR, K.M. Targeting Zinc(II) Signalling to Prevent Cancer. Met. Ions Life Sci. v.18, p.507–529, 2018. doi: https://doi.org/10.1515/9783110470734-023