Cortisol and melatonin aberrations In 2008 the
Endocrine Society published diagnostic guidelines for Cushing's syndrome, wherein they recommended midnight salivary cortisol testing on two consecutive days as one possible initial screening tool. A 2009 review concluded that late-night salivary cortisol testing is a suitable alternative to serum cortisol testing for diagnosing Cushing's syndrome, reporting that both sensitivity and specificity exceeded ninety percent. In 2010 Sakihara,
et al., evaluated the usefulness and accuracy of salivary, plasma, and urinary cortisol levels and determined salivary cortisol to be the "method of choice" for Cushing's syndrome screening. In 2008 Restituto,
et al., found early morning salivary cortisol to be "as good as serum" as an
Addison's disease screening technique. In 2010 Bagcim
et al., determined that saliva
melatonin levels "reflect those in serum at any time of the day" and are a reliable alternative to serum melatonin to study the
pineal physiology in newborns. A 2008
review article described saliva melatonin testing as a "practical and reliable method for field, clinical, and research trials".
Reproductive hormone irregularities A 2009 study examined the use of saliva testing to measure
estradiol,
progesterone,
dehydroepiandrosterone (DHEA), and
testosterone levels in 2,722 individuals (male and female). The researchers confirmed the "good validity of [salivary] sex hormone measurements" and concluded that salivary testing was a good method for testing older adults due to the ease of in-home collection. However, other studies suggest that such tests do not represent either the amount of hormones in the
blood, or their
biological activity. Saliva testing is often used as part of
bioidentical hormone replacement therapy, though it has been criticized for being expensive, unnecessary and meaningless.
Female In 2010 a study identified
luteinizing hormone (LH) as an accurate salivary biomarker of
ovulation in females. Researchers measured various hormones in the saliva throughout the menstrual cycle and found that salivary luteinizing hormone was reliably elevated during the ovulatory period and, for that reason, "salivary LH level is a reliable way to determine ovulation." A 1983 study of various salivary steroid assays showed that daily salivary progesterone measurements "provides a valuable means of assessing ovarian function". A 2001 study involved performing daily saliva collection from healthy subjects and plotting these over the entire menstrual cycle. The researchers determined that salivary estradiol and progesterone curves corresponded to the daily profiles normally observed in blood, although of lesser amplitude. In 1999 researchers determined that ELISA-based saliva testing "can serve as a reliable [method] for estriol determination." A 2007 article reported that the free testosterone measurement, including via saliva assay, represents "the most sensitive biochemical marker supporting the diagnosis of PCOS." In 1990 Vuorento, et al., found that luteal phase defects, wherein progesterone levels decline prematurely within the menstrual cycle, were identified with high frequency using salivary progesterone testing among women with unexplained infertility.
Male In 2009 Shibayama, et al., examined the accuracy of salivary androgen measurement for diagnosing
late-onset hypogonadism (age-related decline in
androgens, often called "andropause"). Researchers determined that the accuracy of saliva testosterone and DHEA measurement exceeded 98.5% and that this method "has satisfactory applicability" in the diagnosis of late-onset hypogonadism. A 2007 study reported a sensitivity and specificity of 100% for salivary testosterone in ruling out hypogonadism and concluded that salivary testosterone is a useful biomarker in the diagnosis of male androgen deficiency. The use of salivary testosterone to screen for hypogonadism has been validated by other studies, including one involving 1454 individuals. Those researchers concluded that salivary testosterone is "an acceptable assay for screening for hypogonadism."
Neoplastic conditions Pancreatic cancer A 2010 study by Zhang, et al., demonstrated that researchers were able to detect
pancreatic cancer with high
sensitivity and specificity (90.0% and 95.0%, respectively) by screening saliva for four specific
mRNA biomarkers. In a 2011 review article that examined pancreatic cancer
biomarkers, Hamade and Shimosegawa concluded that clinical application of saliva biomarker testing is "beneficial for the screening and early detection of pancreatic cancer."
Breast cancer In 2008 Emekli-Alturfan, et al., compared saliva from
breast cancer patients to that from healthy individuals and observed, notably, that breast cancer patients' samples contained
dysplastic cells and reduced
lipid peroxides. A 2000 study compared the salivary levels of a breast cancer marker (HER2/neu) in healthy women, women with benign breast lesions, and women with breast cancer. Researchers found that the salivary (as well as serum) level of this marker was significantly higher in women with breast cancer than in healthy women and women with benign breast lesions; they went on to state that the marker may have potential as a tool for diagnosing breast cancer or detecting its recurrence. A separate study corroborated these findings and further demonstrated that another breast cancer marker (CA15-3) was elevated while the
tumor suppressor protein p53 was reduced in the saliva of women with breast cancer compared to healthy controls and women with benign breast lesions.
Oral cancer In 2010 Jou, et al., found that patients diagnosed with oral
squamous cell carcinoma had elevated levels
transferrin in saliva compared to healthy controls and, moreover, that salivary transferrin measurement using ELISA technique was "highly specific, sensitive, and accurate for the early detection of oral cancer." A 2009 study reported that the levels of two biomarkers,
Cyclin D1 (increased compared to controls) and
Maspin (decreased compared to controls), had sensitivities and specificities of 100% for oral cancer detection when measured in saliva. Saliva testing for specific
mRNAs has been found to possess significant potential for
oral cancer diagnosis. In fact, there is evidence to suggest that saliva RNA diagnostics are slightly superior to serum RNA diagnostics, with the comparative
receiver operating characteristic (ROC) value being 95% for saliva but only 88% for serum.
Glucose dysregulation A 2009 study compared the saliva glucose levels of diabetic patients to those of non-diabetic controls. The authors reported that "salivary [glucose] concentration and excretion were much higher in diabetic patients than in control subjects." In 2009 Rao, et al., investigated salivary biomarkers that could aid identification of
type-2 diabetic individuals. Researchers found that sixty-five proteins, the majority of which are involved in regulating metabolism and immune response, were significantly altered in type-2 diabetics. They further observed that the relative increase of these specific proteins was directly proportional to the severity of disease (i.e., they were somewhat elevated in
pre-diabetics and significantly elevated in diabetics). In 2010 Qvarnstrom, et al., conducted a cross-sectional analysis of 500 individuals and found that an increase in salivary
lysozyme was "significantly associated with metabolic syndrome."
Infectious conditions Human immunodeficiency virus The accuracy of saliva anti-HIV antibody testing has been demonstrated in numerous studies; two recent large-scale studies found both sensitivity and specificity to be 100%. The first of these was published in 2008 by Zelin, et al., and compared saliva antibody testing and serum antibody testing using ELISA technique in 820 individuals. The second study, conducted by Pascoe, et al., compared saliva antibody testing to serum antibody testing using ELISA followed by confirmatory Western Blot analysis in 591 individuals. The accuracy of saliva anti-HIV antibody testing has been confirmed by many additional studies, leading to approval of this method by the U.S. Food & Drug Administration in 2004.
Viral hepatitis Several studies have demonstrated diagnostic potential for salivary hepatitis testing. A 2011 study demonstrated that
HBV surface antigen saliva testing using ELISA had a sensitivity and specificity of 93.6% and 92.6%, respectively. Other studies found that saliva assay for anti-HAV antibodies (
IgM and
IgG) was an effective method to identify
HAV-infected individuals.
Hepatitis C has also been identified using salivary detection methods. Yaari, et al., reported in 2006 that saliva testing for anti-HCV antibodies yielded a sensitivity of 100% and a specificity that was "similar or better" when compared to serum testing.
Parasitic infection A 2010 study found that saliva-based detection of the parasite
Entamoeba histolytica was superior to existing fecal detection methods for patients with E. histolytica-associated
liver abscess. In 2004 El Hamshary and Arafa found that salivary anti-E. histolytica
IgA concentration had "predictive diagnostic value of
intestinal amoebiasis…as well as in tissue amoebiasis." A 1990 study that involved saliva testing for E. histolytica in 223 school children demonstrated a sensitivity and specificity of 85% and 98%, respectively. In 2005 Stroehle, et al., determined that saliva detection of IgG antibodies against
Toxoplasma gondii had a sensitivity and specificity of 98.5% and 100%, respectively. A study published in 1990 demonstrated the diagnostic utility of saliva IgG testing in identifying
neurocysticercosis secondary to
Taenia solium.
Helicobacter pylori infection In a 2005 study, researchers investigated the accuracy of
Helicobacter pylori diagnosis in dyspeptic patients using salivary anti-
H. pylori IgG levels. They determined that saliva testing for
H. pylori antibodies "could be used reliably for screening dyspeptic patients in general practice." That same year Tiwari, et al., examined the accuracy of testing saliva for
H. pylori DNA and how well this correlated with presence of
H. pylori detected via gastric biopsy. Based on their results, researchers concluded that saliva testing could serve as a reliable non-invasive detection method for
H. pylori infection.
Periodontitis A 2009 study conducted by Koss, et al., studied salivary biomarkers of
periodontal disease; their findings revealed that three substances (
peroxidase,
hydroxyproline and
calcium) were significantly increased in the saliva of patients with
periodontitis. A 2010 study found that elevation of three saliva biomarkers (MMP-8, TIMP-1, and ICTP), particularly when analyzed using time-resolved immunofluorometric assay, was suggestive of periodontitis.
Cardiovascular disease CRP: a salivary biomarker for cardiovascular risk . In 2011
Punyadeera, et al., studied "the clinical utility of salivary
C-reactive protein levels in assessing coronary events such as
myocardial infarction in a primary health care setting." Researchers found that saliva CRP levels in cardiac patients were significantly higher when compared to healthy controls. Furthermore, they found that saliva CRP correlated with serum CRP in cardiac patients and, thus, could be a useful tool for "large patient screening studies for risk assessment of coronary events." A necessary and obligatory step in the generation of
nitric oxide by the non-nitric oxide synthase or alternative pathway involves the uptake of nitrate by the
salivary gland, excretion in saliva, and subsequent reduction to nitrite by oral commensal bacteria in the mouth. Salivary nitrite is then further chemically reduced in blood and tissue to
nitric oxide resulting in the lowering of
blood pressure, inhibition of platelet aggregation, increasing cerebral blood flow and flow-mediated dilation, and decreasing oxygen cost during exercise. A principal source of dietary inorganic nitrate, which is reduced to nitric oxide in the body, is from leafy green vegetables. The blood pressure lowering effects of leafy green vegetables, in particular,
spinach and
arugula, are abundant in anti-hypertensive diets such as the
DASH diet. Several papers have shown saliva nitrite levels correlate with
blood nitrite levels which both serve as meaningful surrogates for blood pressure lowering effects. Sobko et al. shows that Japanese traditional diets rich in
leafy vegetables elevated both plasma and saliva nitrite levels with a corresponding decrease in
blood pressure. Webb et al. in 2008 reinforced the obligatory role of saliva in humans to generate
nitric oxide. Here, they showed ingestion of beet juice, a nitrate-rich food, by healthy volunteers markedly reduced blood pressure and by disrupting saliva, either by spitting or interrupting the bioconversion of dietary nitrate to nitrite in the mouth with anti-bacterial mouthwash, the chemical reduction of nitrate to nitrite to nitric oxide with an associated decease in blood pressure was abated. By blocking saliva from recirculating or preventing salivary nitrate from being chemically reduced to nitrite, it prevented a rise in plasma nitrite levels, and blocked a decrease in blood pressure as well as abolished nitric oxide-mediated inhibition of
platelets aggregation confirming the cardio-protective effects were attributable to nitric oxide via the conversion of nitrate to nitrite in saliva. In a series of reports by Ahluwalia and colleagues, they showed in a cross over protocol of 14 volunteers who ingested inorganic nitrates, plasma and saliva nitrite level increased 3 hours post ingestion with a significant reduction of
blood pressure. Nitrate extracted from blood by the salivary gland, accumulates in saliva, which is then reduced to nitric oxide to have a direct blood pressure lowering effect. Decreasing saliva nitrite in volunteers that already had elevated levels, a rise in
systolic and
diastolic blood pressure resulted. Furthermore, pre-hypertensives may be more sensitive to the blood pressure lowering effects of the dietary nitrate-nitrite-nitric oxide pathway. Monitoring the bioconversion of plant-derived nitrate into salivary nitrite serves as a surrogate biomarker for total body nitric oxide status. In 2011 Peeters, et al., identified characteristic aberrations in certain salivary metabolites that were associated with
peanut-allergic individuals when compared to peanut-tolerant controls. In 2003 Vojdani, et al., found that individuals exposed to various allergenic molds and
mycotoxins showed "significantly higher levels of salivary IgA antibodies against one or more mold species."
Chemical substances In 2009 Pink, et al., reported that saliva testing had become so widespread that it had begun to replace urine testing as the standard for detecting
illicit drugs and prescription medications. Shin, et al., reported in 2008 that salivary detection of
ethanol and three of its metabolites (
methanol,
ethylene glycol, and
diethylene glycol) had "relatively high sensitivity and specificity" and that such testing facilitates rapid diagnosis of alcohol intoxication. A 2002 study demonstrated that there was good agreement between saliva and breath ethanol analysis, and that chromatographic saliva ethanol assay is "specific…[and] shows good accuracy and precision." In 2011 Vindenes, et al., investigated the viability of drug abuse monitoring using saliva, comparing this method to urine drug detection. Researchers found that several drug metabolites were detected more frequently in saliva than in urine; this was true for
6-monoacetylmorphine,
amphetamine,
methamphetamine, and N-desmethyldiazepam. This same study showed that saliva testing could detect other drug metabolites, as well, although not as frequently as urine testing; this was the case for morphine, other
benzodiazepines,
cannabis, and
cocaine. ==Selected criticism==