Systematic review of natural and miscellaneous agents for the management of oral mucositis in cancer patients and clinical practice guidelines—part 1: vitamins, minerals, and nutritional supplements

  • Noam YaromEmail author
  • Allan Hovan
  • Paolo Bossi
  • Anura Ariyawardana
  • Siri Beier Jensen
  • Margherita Gobbo
  • Hanan Saca-Hazboun
  • Abhishek kandwal
  • Alessandra Majorana
  • Giulia Ottaviani
  • Monica Pentenero
  • Narmin Mohammed Nasr
  • Tanya Rouleau
  • Anna Skripnik Lucas
  • Nathaniel Simon Treister
  • Eyal Zur
  • Vinisha Ranna
  • Anusha Vaddi
  • Karis Kin Fong Cheng
  • Andrei Barasch
  • Rajesh V. Lalla
  • Sharon Elad
  • On behalf of The Mucositis Study Group of the Multinational Association of Supportive Care in Cancer / International Society of Oral Oncology (MASCC/ISOO)
Special Article



To update the clinical practice guidelines for the use of natural and miscellaneous agents for the prevention and/or treatment of oral mucositis (OM).


A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer / International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible.


A total of 78 papers were identified within the scope of this section, out of which 29 were included in this part, and were analyzed with 27 previously reviewed studies. A new Suggestion was made for oral glutamine for the prevention of OM in head and neck (H&N) cancer patients receiving radiotherapy with concomitant chemotherapy. The previous Recommendation against the use of parenteral glutamine for the prevention of OM in hematopoietic stem cell transplantation (HSCT) patients was re-established. A previous Suggestion for zinc to prevent OM in H&N cancer patients treated with radiotherapy or chemo-radiotherapy was reversed to No Guideline Possible. No guideline was possible for other interventions.


Of the vitamins, minerals, and nutritional supplements studied for the management of OM, the evidence supports a Recommendation against parenteral glutamine in HSCT patients and a Suggestion in favor of oral glutamine in H&N cancer patients for the management of OM.


Oral mucositis Natural Herbal medicine Glutamine Zinc Supersaturated calcium phosphate rinse Guidelines 



The authors are thankful for the medical librarians for their valuable contribution to this project:

Lorraine Porcello, MSLIS, MSIM – Bibby Dental Library, Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA; Daniel A. Castillo, MLIS – Edward G. Miner Library, University of Rochester Medical Center, Rochester, NY, USA.

Compliance with ethical standards

Conflict of interest

Per the MASCC Guidelines Policy, employees of commercial entities were not eligible to serve on this MASCC Guidelines Panel.

The authors disclose no conflict of interest (NY, AH, AA, SBJ, MG, HIH, AK, AM, GO, MP, NMN, TR, ASL, NST, EZ, VR, AV, KF, AB, SE). PB has served an advisory role for AstraZeneca, Helsinn, and Kyowa Kyrin and received grants from Merck, Kyowa Kyrin, and Roche.

RVL has served as a consultant for Colgate Oral Pharmaceuticals, Galera Therapeutics, Ingalfarma SA, Monopar Therapeutics, Mundipharma, and Sucampo Pharma; has received research support to his institution from Galera Therapeutics, Novartis, Oragenics, and Sucampo Pharma; and has received stock in Logic Biosciences.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Noam Yarom
    • 1
    • 2
    Email author
  • Allan Hovan
    • 3
  • Paolo Bossi
    • 4
  • Anura Ariyawardana
    • 5
    • 6
  • Siri Beier Jensen
    • 7
  • Margherita Gobbo
    • 8
  • Hanan Saca-Hazboun
    • 9
  • Abhishek kandwal
    • 10
  • Alessandra Majorana
    • 11
  • Giulia Ottaviani
    • 8
  • Monica Pentenero
    • 12
  • Narmin Mohammed Nasr
    • 13
  • Tanya Rouleau
    • 14
  • Anna Skripnik Lucas
    • 15
  • Nathaniel Simon Treister
    • 16
    • 17
  • Eyal Zur
    • 18
  • Vinisha Ranna
    • 19
  • Anusha Vaddi
    • 20
  • Karis Kin Fong Cheng
    • 21
  • Andrei Barasch
    • 22
  • Rajesh V. Lalla
    • 23
  • Sharon Elad
    • 20
  • On behalf of The Mucositis Study Group of the Multinational Association of Supportive Care in Cancer / International Society of Oral Oncology (MASCC/ISOO)
  1. 1.Oral Medicine UnitSheba Medical CenterTel HashomerIsrael
  2. 2.School of Dental MedicineTel Aviv UniversityTel AvivIsrael
  3. 3.British Columbia Cancer - Vancouver CentreVancouverCanada
  4. 4.Medical Oncology, ASST-Spedali CiviliUniversity of BresciaBresciaItaly
  5. 5.College of Medicine and DentistryJames Cook UniversityCairnsAustralia
  6. 6.Metro South Oral Health, Queensland HealthBrisbaneAustralia
  7. 7.Department of Dentistry and Oral Health, Faculty of HealthAarhus UniversityAarhusDenmark
  8. 8.Division of Oral Medicine and Pathology, Department of Medical, Surgical and Health SciencesUniversity of TriesteTriesteItaly
  9. 9.Al-Maha Cancer foundationBethlehemPalestine
  10. 10.Cancer Research Institute, Himalayan Institute of Medical SciencesSwami Rama Himayalan UniversityDehradunIndia
  11. 11.Department of Medical and Surgical Specialties, Radiological Science and Public HealthDental School University of BresciaBresciaItaly
  12. 12.Department of Oncology, Oral Medicine and Oral Oncology UnitUniversity of TurinTurinItaly
  13. 13.Special Needs Dentistry, Dental Services, Directorate General of Health Services-Muscat GovernorateMinistry of HealthMuscatOman
  14. 14.Dental Oncology Program, Health Sciences NorthNorth East Cancer CenterSudburyCanada
  15. 15.Medical Oncology Service, Department of MedicineNYU Langone Perlmutter Cancer CenterNew YorkUSA
  16. 16.Division of Oral Medicine and DentistryBrigham and Women’s HospitalBostonUSA
  17. 17.Department of Oral Medicine, Infection and ImmunityHarvard School of Dental MedicineBostonUSA
  18. 18.Compounding SolutionsTel-MondIsrael
  19. 19.Department of Oral and Maxillofacial SurgeryThe Mount Sinai HospitalNew YorkUSA
  20. 20.Oral Medicine, Eastman Institute for Oral HealthUniversity of Rochester Medical CenterRochesterUSA
  21. 21.Alice Lee Centre for Nursing Studies, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
  22. 22.Division of OncologyWeill Cornell Medical CollegeNew YorkUSA
  23. 23.Section of Oral MedicineUniversity of Connecticut School of Dental MedicineFarmingtonUSA

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