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Profile in Oral Health: Substances for Targeting Xerostomia by Linda Douglas, RDH

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Nowadays, clinicians encounter increasing numbers of individuals with xerostomia-related problems. According to a recent Hygienetown poll, 73 percent of participants are seeing more patients with xerostomia compared to one year ago.

Salivary lubrication, repair, lavage, antimicrobial and buffering properties contribute significantly to the maintenance of the integrity of the hard and soft oral tissue.1 Saliva also moistens and lubricates the food bolus, and the esophagus. A dry mouth can lead to multiple complications,2 for example: cracked lips, angular cheilitis, fissured tongue, dental hypersensitivity, and caries on roots and cusp tips; plus opportunistic infections such as candidiasis. It can also impair speech, taste, mastication and swallowing. Impaired swallowing (dysphagia) could cause oesophageal damage, and compromise nutritional status; dysphagia might also lead to choking, resulting in pulmonary aspiration of food and pneumonia. These problems require a multifaceted approach to management.

To achieve this, management of salivary gland hypofunction (SGH) and xerostomia can be based on seven main goals:
  1. Hydration (adequate water intake is crucial)
  2. Stimulation of salivary flow
  3. Saliva substitution
  4. Reduce the loss of functional salivary gland tissue
  5. Prevent caries, and promote remineralization
  6. Prevent soft tissue injury and infections
  7. Improve comfort
There are a variety of xerostomia relief preparations available that help to achieve these goals; this article discusses the constituents of dry mouth relief preparations, and the rationales for their use.

Stimulation of Salivary Flow

According to the Commission on Oral Health, Research and Epidemiology, stimulation of secretion has a great advantage of providing the benefits of natural saliva.3 Salivary glands are highly responsive to stimulation of taste, masticatory muscles, and sensory nerves of the oral mucosa and periodontal ligament. Stimulation of salivary flow is valuable for responders, who retain some salivary gland activity; most salivary gland hypofunction cases are responders.

Masticatory stimulation is achieved by chewing sugarfree gum, preferably with xylitol. A regular chewing gum habit also causes a prolonged increase in unstimulated salivary flow rate.4

Gustatory stimulation5 is achieved by using flavorings, sugar substitutes and buffered fruit acids.

Systemic Sialagogues6 might be prescribed, if not contraindicated.

Drug-free options for stimulation of salivary flow include acupuncture,7 electronic stimulation8 and hypnosis.9

Increased salivary secretion aids gastric digestion, as when swallowed, saliva stimulates gastric secretions.

Saliva Substitution

Saliva substitutes are generally formulations that aim to replicate or approximate the composition and functions of natural saliva in order to protect the hard and soft oral tissues, improve comfort, and facilitate speech, mastication and swallowing.

Constituents of Dry Mouth Relief Preparations

  • Most preparations contain a combination of ingredients,10 which work together to achieve the goals of xerostomia management.
  • Water- based products are best, as natural saliva is 99 percent water.
  • Milk proteins and amino acids such as betaine (trimethylglycine) approximate the protein content11 of saliva: they form a protective coating on the hard and soft oral tissue, which lubricates and retains moisture. Mucin-based preparations remain in the mouth for longer than other muco-protective substances, and therefore need to be used less frequently.
  • Oils, for example evening primrose oil, oxygenated glycerol triesters and olive oil also have dry mouth relieving properties: they coat, lubricate and protect the oral mucosa; olive polyphenols may also have plaque inhibiting properties.
  • Folic acid aids healing of trauma and apthous ulcers. Hyaluronic acid12 adds moisture, and may also be beneficial for apthous ulcers.13 Lanolin, beeswax or plant oil products lubricate dry lips.
  • Bicarbonate, calcium and phosphate buffer acids. Calcium and phosphate combined, as in Recaldent, work with fluoride to promote remineralization. Fluoride and Recaldent are also good desensitizing agents, as are potassium nitrate, and Pro-Argin (a complex of arginine and calcium carbonate).
  • Sweeteners, such as anhydrous crystalline maltose,14 buffered fruit acids and various flavorings provide gustatory stimulation of salivary flow. Xylitol15 is a sweetener, which is a valuable component of any protocol for promotion of healthy saliva. It is a non-fermentable crystalline alcohol obtained from birch bark, which, in addition to stimulating salivation, reduces the oral population of Mutans Streptococci. When ingested by Mutans Streptococci, they starve and are rendered unable to replicate. Research on long-term xylitol supplementation has also found that xylitol inhibits growth and inflammatory cytokine expression of porphyromonas gingivalis.16 Xylitol also has a low glycaemic index (7) and has little effect on blood sugar levels.
  • Chamomile tea stimulates salivation, and improves the comfort of a dry mouth. Jaborandi leaf17 is from a plant used in South and Central America to promote saliva production, and green tea polyphenols reportedly reduce free radical damage to the salivary glands.17
  • Hydrophilic, demulcent substances (often with mucilage) such as aloe vera and carrageenan improve comfort. They add moisture, form a protective coating on the oral mucosa, and have a “slippery” feel, which replicates the viscosity of saliva.
  • The enzymes lysozyme, and lactoperoxidase, and an ironbinding protein, lactoferrin, replicate the antimicrobial properties of natural saliva. Peroxidase enhances production of hypothiocyanite, an antibacterial ion present in natural saliva.
  • Synthetic peptides such as Histatin/P-113 have been tested as an antimicrobial component of oral gels.18

Prescription Preparations

The dental surgeon or MD might prescribe the following preparations:

  • Systemic sialagogues such as pilocarpine and cevimeline stimulate salivary flow, and slow the loss of functional salivary gland tissue. These drugs have limitations, due to their contraindications, and side effects, which include flushing, sweating, rhinorrhoea and diarrhea; they are contraindicated for individuals with asthma, acute iritis, acute-angle glaucoma, cardiovascular disease, or a history of kidney or bile stones. In addition, pilocarpine cannot be taken by patients with chronic obstructive pulmonary disease or those taking beta-blockers.
  • Initial research results on cevimeline gargle 19 have been inconsistent.
  • Research is also being conducted on pilocarpine rinses.20 Pilocarpine HCI has been shown to be effective when used as a mouthwash for one minute in healthy individuals. Some clinicians have also prescribed 5mg pilocarpine lollipops for 20 to 30 seconds, approximately every two hours.
  • Amifostine21 is a chemoprotective and radioprotective drug, which is administered intravenously. It acts as a free radical scavenger in the tissues, to reduce the incidence of xerostomia and mucositis resulting from chemotherapy or radiation therapy.
  • Alcohol-free chlorhexidine rinses reduce the oral population of pathogens, cariogenic bacteria and opportunistic micro-organisms.
  • Allopurinol rinse is used for chemotherapy-induced mucositis. It neutralizes uric acid, which is produced as a result of tumor necrosis syndrome.
  • Caphosol is used for for xerostomia and mucositis. It is an electrolyte solution with calcium and phosphate ion. It is anti-inflammatory, and promotes repair of damaged mucosal surfaces by diffusing into intracellular spaces in the epithelium and permeating mucosal lesions.
  • Sucrose sulfate aluminum complex adheres to ulcerated tissue. It is a buffer and is also cytoprotective.

Chronic Candidiasis

This is a common complication of a dry mouth, which can be treated with the following:

  • Systemic anti-fungals - Fluconazole 200mg for three days once per month; this dose reduces the risk of resistance to this medication. Nystatin does not work as well for chronic candidiasis.
  • Oral rinses for burning mouth - Some clinicians prescribe daily prednisone rinses 5mg/5ml for patients with a burning mouth related to chronic candidiasis - this seems counterintuitive, but it can help to control the redness and soreness associated with chronic candidiasis.
    • Flucinomide 0.05% (or various strengths)
    • Clobetasol 0.05%
    • Betamethosone diproprionate 0.05%
    • Tacrolimus 0.01-0.1%
      • absorption
  • Prednisolone 15mg per 5ml
  • Dexamethosone (0.5mg/5ml) presents problems with systemic

The 2011 Cochrane systematic review of topical therapies for dry-mouth management found that there is no strong evidence that any topical therapy is effective for xerostomia relief. Further research utilizing well-designed, randomized controlled trials are required to provide evidence to guide clinical care. However, integrated mouth care systems, for example, combining toothpaste, gel and mouthwash, showed promising results, and chewing gum appears to increase saliva flow in those with residual secretory capacity.22 A multifaceted approach using combinations of the above strategies and substances could be helpful in maintaining oral health and quality of life. There are now many preparations at our disposal. The information in this article could help clinicians and patients to make informed choices.

References
  1. Mandel ID.The role of saliva in maintaining oral homeostasis. J Am Dent Assoc.1989;119:298-304
  2. Dawes C. Physiologic factors affecting salivary flow rate, oral sugar clearance, and the sensation of dry mouth in man. J Dent Res. 1987;66(special issue):648-653
  3. Saliva: its role in health and disease. Working Group 10 of the Commission on Oral Health, Research and Epidemiology (C.O.R.E.) Int Dent J. 1992;42(4 Suppl 2):291-394.
  4. Laurence J. Walsh, Clinical Aspects of salivary biology for the dental clinician:Minim Interv Dent 2008; 1: 7-24
  5. Porter SR, Scully C, Hegarty AM. An update of the etiology and management of xerostomia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:28-46
  6. Fox PC. Salivary enhancement therapies. Caries Res. 2004;38:241-246.
  7. Johnstone PA, Niemtzow RC, Riffenburgh, RH. Acupuncture for xerostomia: clinical update. Cancer. 2002;94:1151-1156
  8. Efficacy and Safety of an Intraoral Electrostimulation Device for Xerostomia Relief: A Multicenter, Randomized Trial; Frank P. Strietzel, Wolff A, et al. J Rheum, Vol. 63, No. 1, January 2011, pp 180-190 DOI 10.1002/art.27766
  9. J Pain Symptom Manage.2009 Jun;37(6):1086-1092.e1. Epub 2009 Jan 31.Hypnosis for postradiation xerostomia in head and neck cancer patients: a pilot study.Schiff E Mogilner JG Sella E Doweck I Hershko O Ben-Arye E Yarom N SourceDepartment of Internal Medicine B, Bnai Zion Medical Center, P.O. Box 4940, Haifa 31048, Israel. eschiff@bezeqint.net
  10. Ship, Mc Cutcheon, Spiivakovsky (2007) Safety and effectiveness of topical dry mouth products containing olive oil, betaine and xylitol in reducing xerostomia for polypharmacy induced dry mouth
  11. Jensdottir et al, J Dent Res 85(3): 226-230, 2006
  12. Yuan J, Tohara H, Mikushi S, et al. The effect of “Oral Wet” for elderly people with xerostomia—the effect of oral rinse containing hialuronan. Kokubyo Gakkai Zasshi. 2005 Mar;72(1):106-10.
  13. Lee JH, Jung JY, Bang D. The efficacy of topical 0.2% hyaluronic acid gel on recurrent oral ulcers: comparison between recurrent aphthous ulcers and the oral ulcers of Behçet’s disease. J Eur Acad Dermatol Venereol. 2008 May;22(5):590-5.
  14. Fox PC, Cummins MJ, Cummins JM. Use of orally administered anhydrous crystalline maltose for relief of dry mouth. J Altern Complement Med. 2001;7:33-43
  15. Linear response of mutans streptococci to increasing frequency of xylitol chewing gum use: a randomized controlled trial [ISRCTN43479664] Kiet A Ly, Peter Milgrom, Marilyn C Roberts, David K Yamaguchi, Marilynn Rothen, and Greg Mueller BMC Oral Health. 2006; 6: 6. Published online 2006 March 24. doi: 10.1186/1472-6831-6-6. PMCID: 1482697
  16. Han SJ, Jeong SY, Nam YJ, Yang KH, Lim HS, Chung J. Xylitol inhibits inflammatory cytokine expression induced by lipopolysaccharide from Porphyromonas gingivalis. Clin Diagn Lab Immunol. 2005 Nov;12(11):1285-91. 11.
  17. Dr. Stephen Hsu, Georgia Health Sciences University College of Dental Medicine. New lozenge clinical trial for dry mouth treatment March 2011
  18. J Clin Periodontol. 2002 Dec;29(12):1051-8. Safety and clinical effects of topical histatin gels in humans with experimental gingivitis. Paquette DW, Simpson DM, Friden P, Braman V, Williams RC.
  19. Y Takagi, Y Kimura, and T Nakamura; Ann Rheum Dis. 2004 June; 63(6): 749. doi: 10.1136/ard.2003.012633. PMCID: 1755032
  20. Bernardi R, Perin C, Becker FI, et al. Effect of pilocarpine mouth wash on salivary flow. Braz J Med Biol Res. 2002; 35(1):105-110
  21. Kouvaris JR, Kouloulias VE, Vlahos LJ. Amifostine: the first selective-target and broad-spectrum radioprotector. Oncologist. 2007 Jun;12(6): 738-47. Review. PMID: 17602063 [PubMed - indexed for MEDLINE]
  22. Cochrane Database Syst Rev.2011 Dec 7;(12):CD008934. doi: 10.1002/14651858.CD008934.pub2. Interventions for the management of dry mouth: topical therapies. Furness S, Worthington HV, Bryan G, Birchenough S, McMillan R, Source Cochrane Oral Health Group, School of Dentistry, The University of Manchester, Coupland III Building, Oxford Rd, Manchester, UK, M13
Author's Bio
Linda Douglas is originally from London, England where she studied dental assisting at the Eastman Dental Hospital and graduated from the Dental Hygiene Program at the Royal Dental Hospital. She has lived and worked in Toronto, Canada for 22 years. Her desire to improve support for xerostomic patients has instigated an in-depth study of saliva and xerostomia management.
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