Saliva
Saliva: A Fountain of Opportunity
Mahvash Navazesh, DMD; Paul Denny, PhD; and Stephen Sobel, DDS
Copyright 2002 Journal of the California Dental Association.
Authors
Mahvash Navazesh, DMD, is an associate professor and chair in the Division of Diagnostic Sciences at the University of Southern California School of Dentistry.
Paul Denny, PhD, is a professor of biochemistry in the Division of Diagnostic Sciences at USC School of Dentistry.
Stephen Sobel, DDS, is an associate professor of clinical dentistry in the Division of Diagnostic Sciences at USC School of Dentistry.
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Saliva continues to demonstrate that it is more complex than generally perceived and has more diagnostic value than is generally appreciated. This article will review some of the components and functions of saliva; discuss its promise as a diagnostic aid; review some of the problems associated with inadequate salivary function; and, it is hoped, enhance oral health care providers’ appreciation of the importance of saliva in everyday clinical practice.
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Saliva, often described as being "99 percent water," mirrors an individual’s health; and the complexity of saliva offers multiple windows of opportunity for monitoring general wellness, assessing oral health and disease, tracking the progression and treatments of systemic disease, assessing risk, and detecting substance abuse.1
Many and various attributes of saliva are routinely referenced in forensic dentistry; but the challenge for exploiting the full potential of saliva for diagnosis, pharmacological monitoring, and risk assessment remains.2
The oral cavity is one of the most important portals into the body. Saliva represents the first line of defense against foreign pathogens as well as commensial residents when high population densities can also be pathogenic. The flow of saliva allows for the constant cleansing of oral tissues with its beneficial properties and provides the fluid current that moves food and microbes out of the oral cavity. The coating property of saliva is complex and can alternatively lubricate tooth surfaces as well as contribute a protective layer to oral soft tissues that protects against desiccation and microbial colonization.2-5
The remineralization capability of saliva depends upon the combination of its uncompromised buffer systems and the systems it employs to maintain calcium and phosphate ions in a supersaturated state relative to the hydroxyapatite of enamel. When the pH of saliva drops to near 5.5 or lower, the equilibrium between the free ions and the mineral shifts to favor demineralization. The antimicrobial properties of saliva depend upon a variety of enzymes and proteins that individually have demonstrated antibacterial, antifungal, and/or antiviral activities. Saliva initiates the general digestive process by the secretion of a variety of digestive enzymes whose role is to degrade food and bacterial remains lingering in the oral cavity. Saliva is also a source of hormones and growth factors.2,6-9
Saliva as a Diagnostic Aid
Saliva is a mixture of ions, small organic molecules, enzymes, and proteins, some in multiprotein complexes and others complexed with other biochemicals.10 Add to this the oral microorganisms and their byproducts, and an ecological system is created that either maintains good oral health or, conversely, contributes to its decline.11
Science is only beginning to recognize the complexity of the ecology and knows even less about how alteration of individual components of the system can affect the whole. The understanding of these interactions may make it possible to manipulate the system in favor of promotion and maintenance of oral health. The type and quantity of oral microbes harbored in the oral cavity may contribute to elevated risk levels for a number of systemic diseases.
Within the past 20 years, more than 2,500 citations have focused on the diagnostic value of oral fluids. Saliva is a fountain of opportunities for innovation and discovery, risk assessment and disease prevention, and pharmacotherapeutic monitoring. The potential is great. Multiple uses for detection of drug abuse and treatment monitoring have been developed. However, exploitation of the full richness of the medium has only begun. Below are some examples of systemic and oral conditions, along with chemotherapeutics, where salivary qualitative and/or quantitative changes have been investigated as potential diagnostic aids.
Systemic Conditions
Saliva has been studied in relation to sundry medical conditions including congenital, autoimmune, endocrine, infectious, and neoplastic disorders. Celiac disease is a congenital disorder of the small intestine that involves malabsorption of gluten. Salivary IgA-AGA measurement has been reported to be a sensitive and specific test for the screening of this disease and monitoring the patient’s adherence to the required gluten-free diet.12,13 Sjögren’s syndrome is a chronic autoimmune disorder that affects many systems, including the salivary and lacrimal glands. Attempts have been made to use xerostomia (dry mouth) and salivary gland hypofunction (reduced saliva flow rate and/or altered sialochemistry) for the clinical diagnosis of this medical condition.14-16 A "yes" response to any of these questions: "Have you had a daily feeling of dry mouth for more than three months?" "Have you had recurrent swollen salivary glands as an adult?" " Do you frequently drink liquid to aid in swallowing dry food?" along with an unstimulated whole saliva flow rate of 0.1 ml/min have been included in the revised European classification criteria for the diagnosis of Sjögren’s syndrome.17 Salivary steroid hormones have been used to assess ovarian function18 and the risk for preterm labor,19,20 to evaluate child health and development,21 and to study mood and cognitive emotional behavior.22
Human immunodeficiency virus infection is one of the best examples for utilizing saliva as a diagnostic aid.23 A saliva test in a self-contained kit is available for HIV screening.24 Saliva is also used for the measurement of other viral pathogens such as hepatitis C, a leading cause of liver cirrhosis;25 hepatitis B surface antigen;26 cytomegalovirus; herpes simplex viruses 6, 7, and 8;27 and epidemiological studies of Epstein Barr virus in schoolchildren.28 Saliva has also received much attention in recent years for its potential role in the diagnosis of Helicobacter pylori, the pathogen associated with peptic ulcer.29 Elevated levels of some salivary markers have been associated with ovarian and breast cancer.30-32 The potential value of saliva as a diagnostic aid for breast cancer detection is under evaluation by FDA.33
Oral Conditions
Saliva can be used to detect oral fungal and periodontal infections, to assess susceptibility to dental caries, and to screen for oral neoplasms. Salivary fungal colony forming units can be used for detection of oral candidiasis.34 The salivary levels of pathogens such as Porphyromonas gingivalis, Streptococcus mutans, and Lactobacillus acidophilus can be utilized in risk assessments for periodontal diseases10 and dental caries.35,36. Elevated levels of some salivary proteins have also been associated with oral squamous cell carcinoma.37 The possibility of oral cancer is also reported to be higher in individuals who have high salivary levels of nitrate and nitrite. Salivary levels of these two factors are significantly associated with the levels of dietary intake.38 The type and quantity of oral microbes harbored in the oral cavity may contribute to elevated risk levels for a number of systemic diseases. Though the evidence rarely extends beyond epidemiological correlation, there is reason to anticipate that there are direct links between uncontrolled oral disease and systemic conditions such as cardiovascular disease, and delivery of low birth weight, premature babies.39-41
Pharmacotherapeutics
Saliva can be used for monitoring the systemic (plasma) levels of medications as well as therapeutic responses to medications. For example, saliva can be used to monitor a patient’s compliance with insulin therapy, psychotherapy,42 and anticancer medications.43 It can also be used for evaluation of illicit drug use, ethanol consumption, recreational drug use, and tobacco consumption.44-47 A comprehensive list of medications easily monitored in saliva is available elsewhere and is not discussed here.2,33
When Production of Saliva Fails
The absence or loss of function of any of the beneficial actions of saliva mentioned above can predispose an individual to oral disease and the systemic cascade that may follow. The importance of saliva is never more clear as when there is too little or none. There is a dramatic impact on oral health as well as a level of discomfort and inconvenience that adversely affects personal freedom and the feeling of well-being.
The quality and quantity of saliva are affected by a broad array of local and systemic conditions as well as by large families of pharmacological agents48-51(Table 1). Bacterial infections, viral infections, sialoliths, and medications may act as local factors in reducing saliva secretion. On the other hand, Sjögren’s syndrome, rheumatoid arthritis, lupus erythematosis, sarcoidosis, cystic fibrosis, Alzheimer’s disease, uncontrolled diabetes, hypertension, strokes, AIDS and HIV infection, and depression are systemic causes for salivary gland hyposecretion.52,53 Some consequences of persistent and severe salivary gland hyposecretion are the onset and rapid progression of dental caries, fungal infection, and intraoral soft tissue changes54,55(Figures 1 through 6). Chronic reduced saliva secretion may lead to depression56 and tooth loss57 and affect an individual’s quality of life.52 Salivary gland hypofunction may go unnoticed by patients and practitioners, because the subjective perception of dry mouth is not always correlated with objective evidence of salivary hypofunction and vice versa. Therefore, it is imperative to include salivary gland assessment as part of everyday practice. Otherwise, practitioners may be faced with the consequences of dry mouth that lead to therapeutic rather than preventive approaches.
The importance of including an oral soft-tissue evaluation and cancer screening when doing a dental examination has long been established and is not questioned by the profession. In view of the effects on one’s quality of life in general, and the potentially disastrous effects on restorative treatment plans in particular, the dental profession must recognize the need and the value of including an evaluation of salivary function with every new dental examination as well as ongoing observations during treatment and recall. Consider as one example the patient with salivary hypofunction who has had extensive full-coverage restorations and is soon found to have severe cervical caries around the restorations. The implications for retreatment, chair time, cost, and possible loss of patient rapport are significant. Table 2 is a flow chart to help practitioners through the logical steps of screening patients for possible salivary gland hypofunction, and the time required is minimal.
This flow chart contains four questions relative to saliva secretion. These questions have been significantly associated with objective evidence of salivary gland hypofunction.58 These questions should be routinely asked of new and recall patients at the time of examination, even if there is no complaint of dry mouth. The clinical changes involving the intraoral and extraoral hard and soft tissues listed in the flow chart have also been successfully utilized for identification of patients with salivary gland hypofunction.55 Practitioners, when performing clinical evaluations, should also observe for objective evidence of salivary hypofunction.
The management of salivary gland hypofunction and its sequelae has been well-documented52,53,59,60 and will not be covered in detail here. The management may include hydration, regular at-home and professional oral prophylaxis and fluoride therapy; medical, nutritional, pharmacotherapeutic, and emotional counseling; and salivary stimulation and substitution as indicated.61-63
Conclusion
The wonders of saliva have recently been appreciated by the media and the health professions.64 Dentistry should support the development and promotion of saliva as a window into wellness and a means for early disease detection that leads to more-effective treatments, risk assessment for future oral and systemic diseases, and a simple, non-invasive alternative to blood and urine tests. The authors envision that a greater understanding of the dynamics of the oral environment mediated by saliva will provide opportunities for developing batteries of multiple analyte tests dedicated to different aspects of oral health, such as an individual’s remineralization potential, caries and periodontal disease risk, and even the types and titers of oral microbes that contribute risk to other diseases or medical procedures.
The value of saliva to humankind will expand during the coming years as more scholars, educators, health care providers, and policy makers come to appreciate its fascinating world.
For more information about saliva, readers are encouraged to visit the following sites:
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To request a printed copy of this article, please contact/Mahvash Navazesh, DMD, USC School of Dentistry, 925 W. 34th St., Room 4320, Los Angeles, CA 90089-0641, or navazesh@usc.edu.
Legends
Figure 1. Fissured and lobulated tongue secondary to salivary gland hypofunction.
Figure 2. Atrophic and erythematous tongue in a patient with dry mouth complaint.
Figure 3. Pseudomembranous candidiasis involving tongue mucosa in a patient with salivary gland hypofunction and uncontrolled diabetes.
Figure 4. Erythematous candidiasis in a patient with salivary gland hypofunction who was on multiple xerogenic medications.
Figure 5. Desiccated mucosa, absence of salivary pool, extensive restorative experience, and recurrent caries in a patient with Sjögren’s syndrome and severe salivary gland hypofunction.
Figure 6. Cervical caries involving multiple maxillary anterior teeth in the patient seen in Figure 5.
Table 1. Common Conditions Associated with Salivary Gland Hypofunction.Systemic Disorders Autoimmune Pharmacotherapeutics Radiotherapy Chemotherapy Medications/Polypharmacy
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