Analysis of salivary fluid and chemosensory functions in patients treated for primary malignant brain tumors.

OBJECTIVES: The frequency and causes of chemosensory (taste and smell) disorders in cancer patients remain under-reported. This study examined the impact of cancer therapy on taste/smell functions and salivary constituents in brain tumor patients. MATERIALS AND METHODS: Twenty-two newly diagnosed patients with primary malignant gliomas underwent 6 weeks of combined modality treatment (CMD) with radiation and temozolomide followed by six monthly cycles of temozolomide. Chemosensory functions were assessed at 0, 3, 6, 10, 18, and 30 weeks with paired samples of saliva collected before and after an oral rinse with ferrous-spiked water. Iron (Fe)-induced oxidative stress was measured by salivary lipid oxidation (SLO); salivary proteins, electrolytes, and metals were determined. Parallel salivary analyses were performed on 22 healthy subjects. RESULTS: Chemosensory complaints of cancer patients increased significantly during treatment (p = 0.04) except at 30 weeks. Fe-induced SLO increased at 10 and 18 weeks. When compared with healthy subjects, SLO, total protein, Na, K, Cu, P, S, and Mg levels, as averaged across all times, were significantly higher (p < 0.05), whereas salivary Zn, Fe, and oral pH levels were significantly lower in cancer patients (p < 0.05). Neither time nor treatment had a significant impact on these salivary parameters in cancer patients. CONCLUSIONS: Impact of CMT treatment on chemosensory functions can range from minimal to moderate impairment. Analysis of SLO, metals, and total protein do not provide for reliable measures of chemosensory dysfunctions over time. CLINICAL RELEVANCE: Taste and smell functions are relevant in health and diseases; study of salivary constituents may provide clues on the causes of their dysfunctions.

Characterization of Metallic Off-Flavors in Drinking Water: Health, Consumption, and Sensory Perception.

Characterization of taste- and flavor-producing metals, namely iron and copper, in drinking water is a multifaceted subject. Both metals are essential nutrients, can be toxic, and are known to produce unpleasant tastes and flavor sensations in drinking water. Ingestion of trace metal contaminants through drinking water is a probable source of human exposure. Biochemical mechanisms of metallic flavor perception have been previously described; however, less is known about how variations in salivary constituents might impact individuals' sensitivities to metallic flavors and beverage consumption behaviors. This research presents findings from in vitro experiments, using artificial human saliva, to better understand the role of salivary lipids and proteins on metallic flavor production as measured by biomarkers of metal-induced oxidative stress. The results indicate that metal-induced lipid oxidation, as measured by thiobarbituric acid reactive substances (TBARS), is dominated by salivary proteins, is slightly inhibited in the presence of salivary nitrite, and is detectable by the TBARS method at and above respective concentrations of 9 µM (0.5 mg/L) and 90 µM (5 mg/L), which are both above the aesthetic standards for iron (0.3 mg/L) and copper (1.0 mg/L) in drinking water. Preliminary study with human subjects indicated that reduction in metallic flavor sensitivity, as measured by the best estimate flavor threshold for ferrous iron among 33 healthy adults aged 19-84 years old (22 females), corresponded with reduced drinking water consumption and increased caloric beverage intake among older subjects (>60 years), as determined by a validated self-reported beverage intake questionnaire. These findings provide insights for further research to examine how salivary constituents can impact humans' sensory abilities in detecting metallic off-flavors in water, and how reduced metallic flavor sensitivity may influence beverage choices and drinking water consumption.

Age-associated variation in sensory perception of iron in drinking water and the potential for overexposure in the human population.

Humans interact with their environment through the five senses, but little is known about population variability in the ability to assess contaminants. Sensory thresholds and biochemical indicators of metallic flavor perception in humans were evaluated for ferrous (Fe(2+)) iron in drinking water; subjects aged 19-84 years participated. Metallic flavor thresholds for individuals and subpopulations based on age were determined. Oral lipid oxidation and oral pH were measured in saliva as potential biochemical indicators. Individual thresholds were 0.007-14.14 mg/L Fe(2+) and the overall population threshold was 0.17 mg/L Fe(2+) in reagent water. Average thresholds for individuals younger and older than 50 years of age (grouped by the daily recommended nutritional guidelines for iron intake) were significantly different (p = 0.013); the population thresholds for each group were 0.045 mg/L Fe(2+) and 0.498 mg/L Fe(2+), respectively. Many subjects >50 and a few subjects <50 years were insensitive to metallic flavor. There was no correlation between age, oral lipid oxidation, and oral pH. Standardized olfactory assessment found poor sensitivity for Fe(2+) corresponded with conditions of mild, moderate, and total anosmia. The findings demonstrate an age-dependent sensitivity to iron indicating as people age they are less sensitive to metallic perception.

In Vitro Evaluation of Iron-Induced Salivary Lipid Oxidation Associated with Exposure to Iron Nanoparticles: Application Possibilities and Limitations for Food and Exposure Sciences.

Zerovalent iron nanotechnologies are widely used for groundwater remediation and increasingly considered for advance oxidation treatment in drinking water applications. Iron nanoparticles have been detected in drinking water systems and considered for food fortification; therefore, the potential for human exposure through ingestion can be a concern. This study aimed to assess whether ingestion of iron nanoparticles from drinking water could be detected through flavor perception using in vitro salivary lipid oxidation as an indicator for metallic flavor perception. Ten female subjects, aged 29-59 years, donated saliva samples for use in the in vitro experiments. Test samples consisted of 1:1 mixture of saliva and bottled drinking water (control) and three treatment solutions, spiked with ferrous sulfate, stabilized zerovalent iron nanoparticles (nZVI), and an aggregated/microsized suspension of mixed zerovalent iron and microsized suspension of iron and iron oxide metal powder, (mZVI). Upon mixing, samples were subjected to 15 min incubation at 37 °C to resemble oral conditions. Salivary lipid oxidation (SLO) was measured in all samples as micromoles of thiobarbituric acid reactive substances (TBARS)/mg Fe. Exposure to iron in all three forms induced significant amount of SLO in all treatment samples as compared to the control (p < 0.0001). The mean SLO levels were the highest in the ferrous treatment, followed by nZVI and mZVI treatments; the differences in the mean SLO levels were significant (p < 0.05). The findings indicate that oral exposure to stabilized ZVI nanoparticles may induce sensory properties different from that of ferrous salt, likely predictive of diminished detection of metallic flavor by humans.

Taste and smell disturbances after brain irradiation: a dose-volume histogram analysis of a prospective observational study.

PURPOSE: Radiation-induced taste and smell disturbances are prevalent in patients receiving brain radiation therapy, although the mechanisms underlying these toxicities are poorly understood. We report the results of a single institution prospective clinical trial aimed at correlating self-reported taste and smell disturbances with radiation dose delivered to defined areas within the brain and nasopharynx. METHODS AND MATERIALS: Twenty-two patients with gliomas were enrolled on a prospective observational trial in which patients underwent a validated questionnaire assessing taste and smell disturbances at baseline and at 3 and 6 weeks after commencement of brain radiation therapy. Fourteen patients with glioblastoma, 3 patients with grade 3 gliomas, and 5 patients with low grade gliomas participated. Median dose to tumor volume was 60 Gy (range, 45-60 Gy). Dose-volume histogram (DVH) analysis was performed for specific regions of interest that were considered potential targets of radiation damage, including the thalamus, temporal lobes, nasopharynx, olfactory groove, frontal pole, and periventricular stem cell niche. The %v10 (percent of region of interest receiving 10 Gy), %v40, and %v60 were calculated for each structure. Data from questionnaires and DVH were analyzed using stepwise regression. RESULTS: Twenty of 22 patients submitted evaluable questionnaires that encompassed at least the entire radiation therapy course. Ten of 20 patients reported experiencing some degree of smell disturbance during radiation therapy, and 14 of 20 patients experienced taste disturbances. Patients reporting more severe taste toxicity also reported more severe toxicities with sense of smell (r(2) = 0.60, P < .006). Tumor location in the temporal lobe predicted for increased severity of taste toxicity (F3, 16 = 1.44, P < .06). The nasopharynx was the only structure in which the DVH data predicted the presence of radiation-induced taste changes (r(2) = 0.28, P < .02). CONCLUSIONS: Radiation-induced taste toxicity appears to be more common in temporal lobe tumors, and may be related to the dose received by the nasopharynx.