Nutraceuticals in Oral Mucositis

by Rajkumar Natekar

Nutraceuticals in Oral Mucositis

by Rajkumar Natekar

by Rajkumar Natekar

The term mucositis applies to the consequences of chemotherapy and radiation therapy in cancer treatment. It pertains to the mucosal damage occurring in the oral cavity, pharyngeal, laryngeal, oesophageal regions, and other gastrointestinal tract areas. About 20% to 40% of patients undergoing conventional chemotherapy and almost all patients who receive head and neck radiation therapy (H&NRT) develop mucositis.[1]

Oral mucositis (OM) results in painful ulcerative lesions that can negatively impact the overall quality of life by restricting essential activities, such as talking, eating, swallowing, and oral hygiene maintenance. OM can trigger an inability to tolerate food or fluids, which leads to malnutrition, dehydration, and weight loss. Immunocompromised patients have a much greater risk because these lesions can get secondarily infected, which may lead to systemic sepsis.

Depending on the severity [2], OM can be classified , as

  1. Tolerable mucositis (grade 1 and 2)
  2. Intolerable mucositis (grade 3 or higher).

A wide variety of molecules have been tried & tested for the OM management – prevention, severity reduction, and symptomatic relief. Naturally occurring compounds have attracted significant attention in this regard since they are perceived to have minimal side effects while helping the mucosa heal faster, which is a much-desired outcome since OM is already an adverse effect.


Zinc is an essential trace element, which is known for its action in tissue repair processes. Zinc induces metallothioneins (zinc-binding proteins) that protect against oxidative damage and inflammatory stress. Metallothionein reduced histological damage and neutrophil infiltration in methotrexate-induced intestinal mucositis in an animal model. [3]

Zinc in OM: [4,5]

Patients who received zinc displayed lower severity, delayed onset, and also had faster healing of OM. The best evidence for zinc comes from a randomized, double-blind, placebo-controlled trial in which zinc supplementation lowered the severity and delayed OM onset in oral cancer patients. Researchers have recommended zinc in oral cancer patients receiving radiation therapy or chemoradiation.

Honey: [6]

Due to its positive effects on wound healing, honey has been studied as a preventive modality in oral mucositis. Honey is recommended for the prevention of intolerable OM due to many of the properties that make it effective – its hygroscopic nature, viscosity, and its acidic pH that prevents bacterial growth on the mucosal surface. Also, honey contains vitamins – ascorbic acid, pantothenic acid, niacin, riboflavin, and minerals such as calcium, copper, iron, magnesium, manganese, phosphorus, potassium, and zinc – that help repair the tissue directly. Other advantages of honey include – being readily available, easy to gargle, non-irritating and sweet, and thus more acceptable to patients, especially children.

Curcumin: [6, 7]

Turmeric or curcumin (Curcuma longa) is a rhizomatous herb often used as a food spice. Curcumin is also traditionally used in oriental medicine to treat several illnesses. A wide range of pharmacological activities of curcumin such as anti-inflammatory, anti-oxidation, lipid-lowering, anti-viral, anti-bacterial, anti-cancer, anticoagulation, anti-fibrosis, anti-atherosclerosis effects, make it a commonly used therapeutic agent, which is further reinforced by low toxicity and minor adverse reactions.

Many studies have found a statistically significant effect of curcumin mouthwash in preventing intolerable OM in cancer patients. [6] However, we still need to determine the safe and tolerable concentration of curcumin mouthwash. Also, we need to determine the efficacy of different concentrations of curcumin mouthwash in oral mucositis prevention.

Chamomilla: [6]

Chamomilla is a commonly used ingredient in a wide variety of health products. It is one of the popular medicinal herbs best-known for its safety and therapeutic properties, such as anti-microbial, anti-inflammatory, antioxidant, and anti-cancer effects. A network analysis published in 2020 found Chamomile to be one of the most effective mouthwashes in the prevention of OM patients.

Glutamine: [8]

Glutamine, a precursor of glutathione, is the most abundant free amino acid in the body, known to play a regulatory role in several cellular processes involved in wound healing and tissue repair. Glutathione is a major intracellular antioxidant that protects cells from damage due to oxidative stress.

A double-blind, randomized, placebo-controlled trial showed that glutamine significantly decreases the severity of chemoradiotherapy-induced mucositis in head and neck cancer patients. [9]

A new study published in 2021 suggested that vitamin E, zinc, and glutamine could effectively prevent and treat OM.[10]

Let us take a look at two meta-analyses published in the year 2020 –

A network meta-analysis [6] published in 2020 compared the preventive effect of ten different types of mouthwashes in the clinical management of intolerable oral mucositis. A literature search was performed, and reports published from 1990 to 2019 focusing on mouthwashes in OM prevention were identified. The authors evaluated thirty-six randomized controlled trials that included a total of 2594 patients. The Bayesian network analysis showed that honey, chamomile, and curcumin-containing mouthwashes were superior to placebo, among the naturally available molecules. The study found that mouthwashes containing these molecules may be the most advantageous in preventing intolerable OM.

The authors of another meta-analysis [11] searched the databases for randomized control trials (RCTs) published from inception until January 2019 on the effects of different oral care solutions in preventing OM.

The network meta-analysis included a total of 28 randomized controlled trials involving 1861 patients. Among the oral care solutions containing natural molecules – honey and curcumin were more effective than placebo. The authors concluded that curcumin and honey might serve as the preferred options for preventing OM and form the basis for its clinical management.



[1] Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, McGuire DB, Migliorati C, Nicolatou-Galitis O, Peterson DE, Raber-Durlacher JE, Sonis ST, Elad S; Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014 May 15;120(10):1453-61. doi: 10.1002/cncr.28592. Epub 2014 Feb 25. Erratum in: Cancer. 2015 Apr 15;121(8):1339. PMID: 24615748; PMCID: PMC4164022.

[2] Rao S, Hegde SK, Rao P, Dinkar C, Thilakchand KR, George T, Baliga-Rao MP, Palatty PL, Baliga MS. Honey Mitigates Radiation-Induced Oral Mucositis in Head and Neck Cancer Patients without Affecting the Tumor Response. Foods. 2017 Sep 6;6(9):77. doi: 10.3390/foods6090077. PMID: 28878156; PMCID: PMC5615289.

[3] Tran CD, Sundar S, Howarth GS. Dietary zinc supplementation and methotrexate-induced small intestinal mucositis in metallothionein-knockout and wild-type mice. Cancer Biol Ther. 2009 Sep;8(17):1662-7. doi: 10.4161/cbt.8.17.9293. Epub 2009 Sep 17. PMID: 19633421.

[4] Lin LC, Que J, Lin LK, Lin FC. Zinc supplementation to improve mucositis and dermatitis in patients after radiotherapy for head-and-neck cancers: a double-blind, randomized study. Int J Radiat Oncol Biol Phys. 2006 Jul 1;65(3):745-50. doi: 10.1016/j.ijrobp.2006.01.015. PMID: 16751063.

[5] Ertekin MV, Koç M, Karslioglu I, Sezen O. Zinc sulfate in the prevention of radiation-induced oropharyngeal mucositis: a prospective, placebo-controlled, randomized study. Int J Radiat Oncol Biol Phys. 2004 Jan 1;58(1):167-74. doi: 10.1016/s0360-3016(03)01562-1. PMID: 14697435.

[6] Zhang X, Sun D, Qin N, Liu M, Zhang J, Li X. Comparative prevention potential of 10 mouthwashes on intolerable oral mucositis in cancer patients: A Bayesian network analysis. Oral Oncol. 2020 Aug;107:104751. doi: 10.1016/j.oraloncology.2020.104751. Epub 2020 May 7. PMID: 32388411.

[7] Nagpal M, Sood S. Role of curcumin in systemic and oral health: An overview. J Nat Sci Biol Med 2013;4:3–7.

[8] Yarom, N., Ariyawardana, A., Hovan, A. et al. Systematic review of natural agents for the management of oral mucositis in cancer patients. Support Care Cancer 21, 3209–3221 (2013).

[9] Tsujimoto T, Yamamoto Y, Wasa M, Takenaka Y, Nakahara S, Takagi T, Tsugane M, Hayashi N, Maeda K, Inohara H, Uejima E, Ito T. L-glutamine decreases the severity of mucositis induced by chemoradiotherapy in patients with locally advanced head and neck cancer: a double-blind, randomized, placebo-controlled trial. Oncol Rep. 2015 Jan;33(1):33-9. doi: 10.3892/or.2014.3564. Epub 2014 Oct 23. PMID: 25351453; PMCID: PMC4254677.

[10] de Sousa Melo A, de Lima Dantas JB, Medrado ARAP, Lima HR, Martins GB, Carrera M. Nutritional supplements in the management of oral mucositis in patients with head and neck cancer: Narrative literary review. Clin Nutr ESPEN. 2021 Jun;43:31-38. doi: 10.1016/j.clnesp.2021.03.030. Epub 2021 Apr 15. PMID: 34024533.

[11] Yu YT, Deng JL, Jin XR, Zhang ZZ, Zhang XH, Zhou X. Effects of 9 oral care solutions on the prevention of oral mucositis: a network meta-analysis of randomized controlled trials. Medicine (Baltimore). 2020 Apr;99(16):e19661. doi: 10.1097/MD.0000000000019661. PMID: 32311938; PMCID: PMC7220734

The article is written by Dr. Chitguppi and is published by Interlink Insight_Vol 20_Issue 2

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