Supportive Care in Cancer

, Volume 17, Issue 11, pp 1331–1343 | Cite as

Saliva substitutes for the treatment of radiation-induced xerostomia—a review

  • Sebastian HahnelEmail author
  • Michael Behr
  • Gerhard Handel
  • Ralf Bürgers
Review Article



The aim of this review is to summarize the in vitro and in vivo evidence on the performance of contemporary saliva substitutes in the treatment of xerostomia and hyposalivation caused by radiation therapy for head and neck malignancies.


A literature search was conducted during July to September 2008 in PubMed, using the query terms “saliva substitute”, “saliva substitute and xerostomia”, “artificial saliva”, and “artificial saliva and xerostomia”; for clinical studies, only studies in patients suffering from radiation-induced xerostomia have been included in the review.

Results and conclusion

Fifty-two studies met the inclusion criteria and were allotted either to the in vitro topics “viscosity”, “lubrication”, “wetting properties”, “antimicrobial effects”, and “enamel and dentin de- and remineralization”, or to the in vivo topics “clinical acceptance” or “influence on plaque formation and oral mucosa and microflora”. The findings suggest that there are significant differences in the performance of various saliva substitutes concerning the review parameters, yet indicate that further in vitro and in vivo studies on the properties of saliva substitutes are necessary.


Saliva substitute Artificial saliva Xerostomia Radiation therapy 


  1. 1.
    Epstein JB, Stevenson-Moore P (1992) A clinical comparative trial of saliva substitutes in radiation-induced salivary gland hypofunction. Spec Care Dentist 12:21–23. doi: 10.1111/j.1754-4505.1992.tb00401.x CrossRefPubMedGoogle Scholar
  2. 2.
    Visch LL, S-Gravenmade EJ, Schaub RMH, van Putten WLJ, Vissink A (1986) A double-blind crossover trial of CMC- and mucin-containing saliva substitutes. Int J Oral Maxillofac Surg 15:395–400PubMedGoogle Scholar
  3. 3.
    Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12. doi: 10.1016/0197-2456(95)00134-4 CrossRefPubMedGoogle Scholar
  4. 4.
    Hatton MN, Levine MJ, Margarone JE, Aguirre A (1987) Lubrication and viscosity features of human saliva and commercially available saliva substitutes. J Oral Maxillofac Surg 45:496–499PubMedCrossRefGoogle Scholar
  5. 5.
    Mellema J, Holterman HJ, Waterman HA, Blom C, s-Gravenmade EJ (1992) Rheological aspects of mucin-containing solutions and saliva substitutes. Biorheology 29:231–249PubMedGoogle Scholar
  6. 6.
    Park MS, Chung JW, Kim YK, Chung SC, Kho HS (2007) Viscosity and wettability of animal mucin solutions and human saliva. Oral Dis 13:181–186. doi: 10.1111/j.1601-0825.2006.01263.x CrossRefPubMedGoogle Scholar
  7. 7.
    Vissink A, Waterman HA, s-Gravenmade EJ, Panders AK, Vermey A (1984) Rheological properties of saliva substitutes containing mucin, carboxymethylcellulose or polyethylenoxide. J Oral Pathol 13:22–28. doi: 10.1111/j.1600-0714.1984.tb01397.x CrossRefPubMedGoogle Scholar
  8. 8.
    Corcoran RA, Stovell AG, Urquhart D, Chui T, Richardson M (2006) Evaluation of a combined polymer system for use in relieving the symptoms of xerostomia. J Clin Dent 17:34–38PubMedGoogle Scholar
  9. 9.
    Van der Reijden WA, Veerman ECI, Amerongen AVN (1994) Rheological properties of commercially available polysaccharides with potential use in saliva substitutes. Biorheology 31:631–642PubMedGoogle Scholar
  10. 10.
    Olsson H, Axéll T (1991) Objective and subjective efficacy of saliva substitutes containing mucin and carboxymethylcellulose. Scand J Dent Res 99:316–319PubMedGoogle Scholar
  11. 11.
    Christersson CE, Lindh L, Arnebrant T (2000) Film-forming properties and viscosities of saliva substitutes and human whole saliva. Eur J Oral Sci 108:418–425. doi: 10.1034/j.1600-0722.2000.108005418.x CrossRefPubMedGoogle Scholar
  12. 12.
    Aguirre A, Mendoza B, Reddy MS, Scannapieco FA, Levine MJ, Hatton MN (1989) Lubrication of selected salivary molecules and artificial saliva. Dysphagia 4:95–100. doi: 10.1007/BF02407152 CrossRefPubMedGoogle Scholar
  13. 13.
    Vissink A, De Jong HP, Busscher HJ, Arends J, s-Gravenmade EJ (1986) Wetting properties of human saliva and saliva substitutes. J Dent Res 65:1121–1124PubMedGoogle Scholar
  14. 14.
    Reeh ES, Douglas WH, Levine MJ (1996) Lubrication of saliva substitutes at enamel-to-enamel contacts in an artificial mouth. J Prosthet Dent 75:649–656. doi: 10.1016/S0022-3913(96)90251-6 CrossRefPubMedGoogle Scholar
  15. 15.
    Aydin AK, Terzioglu H, Ulubayram K, Hasirci N (1997) Wetting properties of saliva substitutes on acrylic resin. Int J Prosthodont 10:473–477PubMedGoogle Scholar
  16. 16.
    Wolinsky LE, Seto B, Cerveny R (1985) Effect of saliva substitutes upon binding of selected oral bacteria to hydroxyapatite. Caries Res 19:507–511PubMedGoogle Scholar
  17. 17.
    Hahnel S, Rosentritt M, Handel G, Bürgers R (2008) Influence of saliva substitute films on initial Streptococcus mutans adhesion to enamel and dental substrata. J Dent 36:977–983. doi: 10.1016/j.jdent.2008.08.004 CrossRefPubMedGoogle Scholar
  18. 18.
    Sugiura Y, Soga Y, Tanimoto I, Kokeguchi S, Nishide S, Kono K et al (2008) Antimicrobial effects of the saliva substitute, Oralbalance®, against microorganisms from oral mucosa in the hematopoietic cell transplantation period. Support Care Cancer 16:421–424. doi: 10.1007/s00520-007-0391-z CrossRefPubMedGoogle Scholar
  19. 19.
    Ruissen ALA, Groenink J, Lommerse CH, Van’t Hof W, Veerman ECI, Amerongen AVN (2002) Effects of carbohydrate polymers applicable in saliva substitutes on the anti-Candida activity of a histatin-derived peptide. Arch Oral Biol 47:749–756. doi: 10.1016/S0003-9969(02)00063-8 CrossRefPubMedGoogle Scholar
  20. 20.
    Smith G, Smith AJ, Shaw L, Shaw MJ (2001) Artificial saliva substitutes and mineral dissolution. J Oral Rehabil 28:728–731. doi: 10.1046/j.1365-2842.2001.00803.x CrossRefPubMedGoogle Scholar
  21. 21.
    Kielbassa AM, Parichereh Shohadai S, Schulte-Mönting J (2000) Effect of saliva substitutes on mineral content of demineralized and sound dental enamel. Support Care Cancer 9:40–47. doi: 10.1007/s005200000148 CrossRefGoogle Scholar
  22. 22.
    Meyer-Lueckel H, Schulte-Mönting J, Kielbassa AM (2002) The effect of commercially available saliva substitutes on predemineralized bovine dentin in vitro. Oral Dis 8:192–198. doi: 10.1034/j.1601-0825.2002.01762.x CrossRefPubMedGoogle Scholar
  23. 23.
    Shannon IL, Trodahl JN, Starcke EN (1978) Remineralization of enamel by a saliva substitute designed for use by irradiated patients. Cancer 41:1746–1750. doi: 10.1002/1097-0142(197805)41:5<1746::AID-CNCR2820410515>3.0.CO;2-C CrossRefPubMedGoogle Scholar
  24. 24.
    Vissink A, s-Gravenmade EJ, Gelhard TBFM, Panders AK, Franken MH (1985) Rehardening properties of mucin- or CMC-containing saliva substitutes on softened human enamel. Caries Res 19:212–218PubMedCrossRefGoogle Scholar
  25. 25.
    Joyston-Bechal S, Kidd EAM (1987) The effect of three commercially available saliva substitutes on enamel in vitro. Br Dent J 163:187–190. doi: 10.1038/sj.bdj.4806238 CrossRefPubMedGoogle Scholar
  26. 26.
    Van der Reijden WA, Buijs MJ, Damen JJM, Veerman ECI, ten Cate JM, Amerongen AV (1997) Influence of polymers for use in saliva substitutes on de- and remineralization of enamel in vitro. Caries Res 31:216–223PubMedGoogle Scholar
  27. 27.
    Meyer-Lueckel H, Hopfenmuller W, von Klinggraf D, Kielbassa AM (2006) Microradiographic study on the effects of mucin-based solutions used as saliva substitutes on demineralised bovine enamel in vitro. Arch Oral Biol 51:541–547. doi: 10.1016/j.archoralbio.2006.01.006 CrossRefPubMedGoogle Scholar
  28. 28.
    Turssi CP, Lima RQV, Faraoni-Romano JJ, Serra MC (2006) Rehardening of caries-like lesions in root surfaces by saliva substitutes. Gerodontology 23:226–230. doi: 10.1111/j.1741-2358.2006.00117.x CrossRefPubMedGoogle Scholar
  29. 29.
    Gelhard TBFM, Fidler V, s-Gravenmade EJ, Vissink A (1983) Remineralization of softened human enamel in mucin- or CMC-containing artificial salivas. J Oral Pathol 12:336–341. doi: 10.1111/j.1600-0714.1983.tb00345.x CrossRefPubMedGoogle Scholar
  30. 30.
    Meyer-Lueckel H, Umland N, Hopfenmuller W, Kielbassa AM (2004) Effect of mucin alone and in combination with various dentifrices on in vitro remineralization. Caries Res 38:478–483. doi: 10.1159/000079630 CrossRefPubMedGoogle Scholar
  31. 31.
    Meyer-Lueckel H, Tschoppe P, Kielbassa AM (2006) Linseed based saliva substitutes and their effect on mineral dissolution of predemineralized bovine dentin in vitro. J Dent 34:750–756Google Scholar
  32. 32.
    Meyer-Lueckel H, Tschoppe P, Hopfenmuller W, Stenzel WR, Kielbassa AM (2006) Effect of polymers used in saliva substitutes on demineralised bovine enamel and dentin. Am J Dent 19:308–312PubMedGoogle Scholar
  33. 33.
    Meyer-Lueckel H, Chatzidakis AJ, Kielbassa AM (2007) Effect of various calcium/phosphates ratios of carboxymethylcellulose-based saliva substitutes on mineral loss of bovine enamel in vitro. J Dent 35:851–857. doi: 10.1016/j.jdent.2007.08.006 CrossRefPubMedGoogle Scholar
  34. 34.
    Shannon IL, McCrary BR, Starcke EN (1977) A saliva substitute for use by xerostomic patients undergoing radiotherapy to the head and neck. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 44:656–661Google Scholar
  35. 35.
    Shannon IL, Edmonds EJ (1978) Effect of fluoride concentration on rehardening of enamel by a saliva substitute. Int Dent J 28:421–426PubMedGoogle Scholar
  36. 36.
    Meyer-Lueckel H, Kielbassa AM (2006) Influence of calcium phosphates added to mucin-based saliva substitutes on bovine dentin. Quintessence Int 37:537–544Google Scholar
  37. 37.
    Meyer-Lueckel H, Tschoppe P, Kielbassa AM (2006) Effect of various Ca2+/PO43− concentrations of linseed-based saliva substitutes on enamel in vitro. J Oral Rehabil 33:760–766. doi: 10.1111/j.1365-2842.2006.01652.x CrossRefPubMedGoogle Scholar
  38. 38.
    Tschoppe P, Meyer-Lueckel H, Kielbassa AM (2008) Effect of carboxymethylcellulose-based saliva substitutes on predemineralised dentin evaluated by microradiography. Arch Oral Biol 53:250–256. doi: 10.1016/j.archoralbio.2007.10.001 CrossRefPubMedGoogle Scholar
  39. 39.
    Ownby HE (1982) Use of a saliva substitute in postradiation xerostomic patients. Ky Dent J 34(19–20):22–24Google Scholar
  40. 40.
    Nakamoto RY (1979) Use of a saliva substitute in postradiation xerostomia. J Prosthet Dent 42:539–542. doi: 10.1016/0022-3913(79)90249-X CrossRefPubMedGoogle Scholar
  41. 41.
    Jellema AP, Langendijk H, Bergenhenegouwen L, van der Reijden W, Leemans R, Smeele L et al (2001) The efficacy of Xialine® in patients with xerostomia resulting from radiotherapy for head and neck cancer: a pilot-study. Radiother Oncol 59:157–160. doi: 10.1016/S0167-8140(01)00336-X CrossRefPubMedGoogle Scholar
  42. 42.
    Momm F, Volegova-Neher NJ, Schulte-Mönting J, Guttenberger R (2005) Different saliva substitutes for treatment of xerostomia following radiotherapy. Strahlenther Onkol 181:231–236. doi: 10.1007/s00066-005-1333-7 CrossRefPubMedGoogle Scholar
  43. 43.
    Walizer EM, Ephraim PM (1996) Double-blind cross-over controlled clinical trial of vegetable oil versus Xerolube for xerostomia: an expanded study abstract. ORL Head Neck Nurs 14:11–12PubMedGoogle Scholar
  44. 44.
    Vissink A, s-Gravenmade EJ, Panders AK, Vermey A, Petersen JK, Visch LL et al (1983) A clinical comparison between commercially available mucin- and CMC-containing saliva substitutes. Int J Oral Surg 12:232–238. doi: 10.1016/S0300-9785(83)80048-9 CrossRefPubMedGoogle Scholar
  45. 45.
    Johansson G, Andersson G, Attström R, Glantz PO, Larsson K (1994) The effect of Salinum on the symptoms of dry mouth: a pilot study. Gerodontology 11:46–49. doi: 10.1111/j.1741-2358.1994.tb00102.x CrossRefPubMedGoogle Scholar
  46. 46.
    Andersson G, Johansson G, Attström R, Edwardsson S, Glantz PO, Larsson K (1995) Comparison of the effect of the linseed extract Salinum® and a methyl cellulose preparation on the symptoms of dry mouth. Gerodontology 12:12–17. doi: 10.1111/j.1741-2358.1995.tb00124.x CrossRefPubMedGoogle Scholar
  47. 47.
    Regelink G, Vissink A, Reintsema H, Nauta JM (1998) Efficacy of a synthetic polymer saliva substitute in reducing oral complaints of patients suffering from irradiation-induced xerostomia. Quintessence Int 29:383–388PubMedGoogle Scholar
  48. 48.
    Dirix P, Nuyts S, Poorten VV, Delaere P, van den Bogaert W (2007) Efficacy of the BioXtra dry mouth care system in the treatment of radiotherapy-induced xerostomia. Support Care Cancer 15:1429–1436. doi: 10.1007/s00520-006-0210-y CrossRefPubMedGoogle Scholar
  49. 49.
    Warde P, Kroll B, O’Sullivan B, Aslanidis J, Tew-George E, Waldron J et al (2000) A phase II study of Biotene in the treatment of postradiation xerostomia in patients with head and neck cancer. Support Care Cancer 8:203–208. doi: 10.1007/s005200050286 CrossRefPubMedGoogle Scholar
  50. 50.
    Epstein JB, Emerton S, Le ND, Stevenson-Moore P (1999) A double-blind crossover trial of Oral Balance gel and Biotene® toothpaste versus placebo in patients with xerostomia following radiation therapy. Oral Oncol 35:132–137. doi: 10.1016/S1368-8375(98)00109-2 CrossRefPubMedGoogle Scholar
  51. 51.
    Nagy K, Urban E, Fazekas O, Thurzo L, Nagy E (2007) Controlled study of lactoperoxidase gel on oral flora and saliva in irradiated patients with oral cancer. J Craniofac Surg 18:1157–1164CrossRefPubMedGoogle Scholar
  52. 52.
    Shahdad SA, Taylor C, Barclay SC, Steen IN, Preshaw PM (2005) A double-blind, crossover study of Biotène Oralbalance and BioXtra systems as salivary substitutes in patients with post-radiotherapy xerostomia. Eur J Cancer Care (Engl) 14:319–326. doi: 10.1111/j.1365-2354.2005.00587.x CrossRefGoogle Scholar
  53. 53.
    Johansson G, Andersson G, Attstöm R, Edwardsson S (2000) Oral mucous membrane flora in patients using saliva substitutes. Gerodontology 17:87–90. doi: 10.1111/j.1741-2358.2000.00087.x CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Sebastian Hahnel
    • 1
    Email author
  • Michael Behr
    • 1
  • Gerhard Handel
    • 1
  • Ralf Bürgers
    • 1
  1. 1.Department of Prosthetic DentistryRegensburg University Medical CenterRegensburgGermany

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