The Tryptophan/Kynurenine Pathway: A Novel Cross-Talk between Nutritional Obesity, Bariatric Surgery and Taste of Fat.

Diet-induced obesity (DIO) reduces the orosensory perception of lipids in rodents and in some humans. Although bariatric surgery partially corrects this alteration, underlying mechanisms remain poorly understood. To explore whether metabolic changes might explain this fat taste disturbance, plasma metabolome analyses, two-bottle choice tests and fungiform papillae (Fun) counting were performed in vertical sleeve gastrectomized (VSG) mice and sham-operated controls. An exploratory clinic study was also carried out in adult patients undergone a VSG. In mice, we found that (i) the VSG reduces both the plasma neurotoxic signature due to the tryptophan/kynurenine (Trp/Kyn) pathway overactivation and the failure of fat preference found in sham-operated DIO mice, (ii) the activity of Trp/Kyn pathway is negatively correlated to the density of Fun, and (iii) the pharmacological inhibition of the Kyn synthesis mimics in non-operated DIO mice the positive effects of VSG (i.e., decrease of Kyn synthesis, increase of Fun number, improvement of the fat taste perception). In humans, a reduction of the plasma Kyn level is only found in patients displaying a post-surgery improvement of their fat taste sensitivity. Altogether these data provide a plausible metabolic explanation to the degradation of the orosensory lipid perception observed in obesity.

Self-reported Taste and Smell Disorders in Patients with COVID-19: Distinct Features in China.

Last December 2019, a cluster of viral pneumonia cases identified as coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. We aimed to explore the frequencies of nasal symptoms in patients with COVID-19, including loss of smell and taste, as well as their presentation as the first symptom of the disease and their association with the severity of COVID-19. In this retrospective study, 1206 laboratory-confirmed COVID-19 patients were included and followed up by telephone one month after discharged from Tongji Hospital, Wuhan. Demographic data, laboratory values, comorbidities, symptoms, and numerical rating scale scores (0-10) of nasal symptoms were extracted from the hospital medical records, and confirmed or reevaluated by the telephone follow-up. From patients (n=1172) completing follow-up, 199 (17%) subjects had severe COVID-19 and 342 (29.2%) reported nasal symptoms. 20.6% COVID-19 patients had loss of taste (median score=6), while 11.4% had loss of smell (median score=5). Loss of taste scores, but not loss of smell scores, were significantly increased in severe vs. non-severe COVID-19 patients. Interleukin (IL)-6 and lactose dehydrogenase (LDH) serum levels were positively correlated with loss of taste scores. About 80% of COVID-19 patients recovered from smell and taste dysfunction in 2 weeks. In this cohort, only 1 out of 10 hospital admitted patients had loss of smell while 1 out of 5 reported loss of taste which was associated to severity of COVID-19. Most patients recovered smell and taste dysfunctions in 2 weeks.

The prognostic role of IL-10 in non-severe COVID-19 with chemosensory dysfunction.

OBJECTIVES: Olfactory and gustatory dysfunction (OD/GD) are now recognized as typical symptoms of COVID-19 infection. However, their pathogenesis remains unclear and no clear prognostic factors have been identified. We have analyzed a cohort of mild/moderate hospitalized patients to identify possible clinical or immunological predictors of recovery from OD/GD. METHODS: Clinical and biological parameters were reviewed along with associated comorbidities. Chemosensory Complaint Score was administered on admission and 30 days after the first negative swab. Unpaired Wilcoxon and chi-squared tests were used to compare the variables in the patients who recovered versus those who did not. RESULTS: From a cohort of 119 hospitalized patients, 43 (36%) reported OD/GD on admission. 60.6% had a full recovery from OD and 69.2% from GD. Only the concentration of IL-10 on admission emerged as significantly associated with recovery of taste (p = 0.041) while allergic respiratory disease was more prevalent in the group who did not recover from OD (p = 0.049) and GD (p = 0.007). CONCLUSION: These findings suggest that COVID-19 associated OD/GD is an inflammatory-mediated condition and that clinical and immunological parameters could predict the evolution of these symptoms.

Taste and Smell Disorders in COVID-19 Patients: Role of Interleukin-6.

The rapid recovery of smell and taste functions in COVID-19 patients could be attributed to a decrease in interleukin-6 levels rather than central nervous system ischemic injury or viral damage to neuronal cells. To correlate interleukin-6 levels in COVID-19 patients with olfactory or gustatory dysfunctions and to investigate the role of IL-6 in the onset of these disorders, this observational study investigated 67 COVID-19 patients with taste or smell disorders or both, who did not require intensive care admission, admitted at COVID Hospital of Policlinico of Bari from March to May 2020. Interleukin-6 was assayed in COVID-19 patients with taste or smell disturbances at the time of admission and at the time of swab negativization. At the same time, patients have been given a specific survey to evaluate the severity of taste and smell disturbances. Of 125 patients with smell or taste dysfunctions at onset of disease, 67 fulfilled the inclusion criteria, while 58 were excluded because 35 of them required intensive care admission, 5 were unable to answer, 5 died, 7 had finished chemotherapy recently, and 5 refused to participate. The evaluation of taste and smell disorders was carried out using a survey performed at the time of admission and at the time of swab negativization. Sinonasal outcome test 22 (SNOT-22) was used as a reference for olfactory function assessment, and Taste and Smell Questionnaire Section of the US NHANES 2011-2014 protocol (CDC 2013b) was used as reference for gustatory function assessment. A venous blood sample was taken for each patient to measure IL-6 levels upon entry and at swab negativization. Interleukin-6 levels in COVID-19 patients in relation to olfactory or gustatory disorders were correlated from the time of their admission to the time of swab negativization. Statistically significant correlations were obtained between the decrease of interleukin-6 levels and the improvement of smell (p value < 0.05) and taste (p = 0.047) functions at swab negativization. The acquired results demonstrate the key role of interleukin-6 in the pathogenesis of chemosensitive disorders in COVID-19 patients.

Gustatory Function and the Uremic Toxin, Phosphate, Are Modulators of the Risk of Vascular Calcification among Patients with Chronic Kidney Disease: A Pilot Study.

Patients with chronic kidney disease (CKD) have an increased risk of vascular calcification (VC), including aortic arch calcification (AAC). Few investigated the influence of gustatory function on the probability of having VC. We examined whether gustatory function results modulated the probability of having VC in patients with CKD. We prospectively enrolled adults with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2), with their AAC rated semi-quantitatively and gustatory function assessed by objective and subjective approaches. Multiple logistic regression was used to analyze the relationship between gustatory function results and AAC. Those with AAC had significantly better objective gustatory function in aggregate scores (p = 0.039) and categories (p = 0.022) and less defective bitter taste (p = 0.045) and scores (p = 0.037) than those without. Multiple regression analyses showed that higher aggregate scores (odds ratio (OR) 1.288, p = 0.032), or better gustatory function, and higher bitter taste scores (OR 2.558, p = 0.019) were each associated with a higher probability of having AAC among CKD patients; such an association was modulated by serum phosphate levels. In conclusion, better gustatory function was independently correlated with having AAC among CKD patients. A follow-up of VC severity may be an underrecognized component of care for CKD patients with a preserved gustatory function.

The Association Between Taste Impairment and Serum Zinc Concentration in Adult Patients With Type 2 Diabetes.

OBJECTIVES: In this study, we aimed to elucidate the association between taste acuity and serum zinc concentration in patients with type 2 diabetes. METHODS: We enrolled 29 patients who were hospitalized and asked them to attend a 2-week diabetes education program. Fasting blood samples were obtained on the morning of the first day and 2 weeks after hospitalization. The acuity of sweet, salty, sour or bitter taste was evaluated by a filter-paper disc method. Correlations among taste acuity, glycemic control and serum zinc concentration were analyzed using the Spearman rank correlation coefficient. RESULTS: The following parameters (mean ± standard deviation) were improved after 2 weeks' hospitalization: taste acuity (sweet: 3.5±1.0 to 2.9±1.1; salty: 3.3±1.1 to 2.6±1.0; sour: 3.6±1.2 to 2.7±0.8; and bitter: 3.3±1.3 to 2.7±1.1; all p<0.001); glycemic control (fasting plasma glucose, 9.4±3.0 to 7.1±1.8 mmol/L, and glycoalbumin, 26.3±7.7 to 22.7±5.9 %; both p<0.001); and serum zinc concentration (1.2±0.2 to 1.3±0.2 mmol/L; p<0.001). Sour and bitter taste acuity were significantly associated with serum zinc concentration (sour, r=-0.50, p=0.005; bitter, r=-0.40, p=0.033). CONCLUSIONS: Glycemic control, serum zinc concentration and taste acuity were improved after the short-duration education program. Sour and bitter taste acuity were significantly associated with serum zinc concentrations.

Smell and Taste Dysfunction Is Associated with Higher Serum Total Cholesterol Concentrations in Chinese Adults.

Background: Several lipid-related hormones and peptides, such as glucagon-like peptide-1 and leptin, are involved in the regulation of taste and smell function. However, to our knowledge, it remains unknown whether these chemosensory functions are associated with lipid profiles.Objective: We examined the cross-sectional association between taste and smell dysfunction and blood cholesterol concentrations.Methods: With the use of a questionnaire, we assessed chronic smell and taste dysfunction in 12,627 Chinese participants (10,418 men and 2209 women; mean age: 54.4 y) who did not take hypolipidemic agents. Participants were categorized into 3 groups based on the number of smell and taste dysfunctions, ranging from 0 (best) to 2 (worst). A general linear model was used to test differences in serum concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides (TGs) across groups with different smell and taste status after adjusting for age, sex, education, occupation, smoking, drinking, obesity, and history of cardiovascular disease, cancer, and head injury.Results: The prevalence of smell and taste dysfunction was 2.4% and 1.2%, respectively. Worse smell and taste dysfunction was associated with higher total cholesterol concentrations (P-trend = 0.005). No significant differences were observed in LDL cholesterol, HDL cholesterol, and TG concentrations across groups with different numbers of chemosensory dysfunctions (P-trend > 0.1 for all). The associations between chemosensory dysfunction and total cholesterol concentrations were more pronounced in participants aged ≤60 y and in those who were nonsmokers relative to their counterparts (P-interaction < 0.05 for all).Conclusions: In this large cross-sectional study, chemosensory dysfunction was associated with higher serum total cholesterol concentrations among Chinese adults. Prospective studies are needed to investigate the temporal relation between these chemosensory dysfunctions and hypercholesterolemia.

Sweet taste disorder and vascular complications in patients with abnormal glucose tolerance.

BACKGROUND: It remains unknown whether taste disorders can be a risk factor for micro- and macro-vascular diseases in patients with abnormal glucose tolerance. METHODS: A cross-sectional study in a nationally representative samples of 848 and 849 US adults (aged ≥40years) with diabetes or prediabetes who had sweet and salt taste disorders, respectively, from the National Health and Nutrition Examination Survey 2011-2012. RESULTS: Among the study population, 5.7% had sweet taste disorder and 8.6% had salt taste disorder. These data correspond to approximately 1.5 million and 1.8 million individuals with abnormal glucose tolerance aged 40years or older in the US population, respectively. In the adjusted model, sweet taste disorder was significantly associated with complication of ischemic heart disease (adjusted odds ratio [OR], 2.45; 95% confidence interval [CI], 1.03-5.81; P=0.04). Moreover, sweet taste disorder in patients with diabetes was significantly associated with diabetic retinopathy (adjusted OR, 2.89; 95% CI, 1.09-7.69; P=0.03) and diabetic nephropathy (adjusted OR, 3.17; 95% CI, 1.07-9.36; P=0.03). Meanwhile, salt taste disorder was not significantly associated with diabetic retinopathy, diabetic nephropathy, ischemic heart disease, or stroke. Total sugar intake was significantly higher in patients with sweet taste disorder than in those without it, whereas total daily intake of carbohydrate did not differ significantly. No significant association was observed between salt taste disorder and daily intake of sodium after multivariate analysis. CONCLUSIONS: Sweet taste disorder in patients with abnormal glucose tolerance was associated with increased sugar intake and vascular complications.

Validity of the copper/zinc ratio as a diagnostic marker for taste disorders associated with zinc deficiency.

Although zinc (Zn) deficiency is often suspected in patients with taste disorders, it may be difficult to diagnose Zn deficiency, especially in patients without any clear risk factors. Accordingly, the aim of the present study was to detect possible markers for taste disorders or zinc deficiency. To achieve this aim, we analyzed data obtained from 122 Japanese men who were not using medicines and had no diseases requiring treatment. We evaluated the following factors: awareness of dysgeusia; salty taste recognition threshold (SRT); the serum concentrations of Zn, copper (Cu), iron, alkaline phosphatase, and albumin; and the Cu/Zn ratio. The serum Cu/Zn ratio was positively correlated with the both the SRT and the awareness of dysgeusia. The serum Zn concentration was not correlated with the SRT or the awareness of dysgeusia in univariate analyses. However, in multivariate logistic regression, the serum Zn concentration was associated with the awareness of dysgeusia. In conclusion, the serum Cu/Zn ratio is a good diagnostic marker for taste disorders and the value of 1.1 may be a threshold level for detecting taste disorders.

Smell-taste dysfunctions in extreme weight/eating conditions: analysis of hormonal and psychological interactions.

(1) The objective of this study is to analyze differences in smell-taste capacity between females in extreme weight/eating conditions (EWC) and (2) to explore the interaction between smell/taste capacity, gastric hormones, eating behavior and body mass index (BMI). The sample comprised 239 females in EWC [64 Anorexia nervosa (AN) and 80 age-matched healthy-weight controls, and 59 obese and 36 age-matched healthy-weight controls]. Smell and taste assessments were performed through "Sniffin' Sticks" and "Taste Strips," respectively. The assessment measures included the eating disorders inventory-2, the symptom check list 90-revised, and The Dutch Eating Behavior Questionnaire, as well as peptides from the gastrointestinal tract [Ghrelin, peptide YY, cholecystokinin]. Smell capacity was differentially associated across EWC groups. Smell was clearly impaired in obese participants and increased in AN (hyposmia in Obesity was 54.3 and 6.4 % in AN), but taste capacity did not vary across EWC. Ghrelin levels were significantly decreased in obese subjects and were related to smell impairment. EWC individuals showed a distinct smell profile and circulating ghrelin levels compared to controls. Smell capacity and ghrelin may act as moderators of emotional eating and BMI.

Linkages of biomarkers of zinc with cognitive performance and taste acuity in adolescent girls.

A cross-sectional study (n = 403) was conducted to examine the relationship of plasma zinc (PZ) and erythrocyte zinc (EZ) levels with cognitive performance and taste acuity for salt in Indian adolescent girls. PZ, EZ and hemoglobin were estimated in schoolgirls (10-16 years). Cognitive performance was assessed by simple-reaction-time (SRT), recognition-reaction-time (RRT), visual-memory, Raven's Progressive Matrices (RPM) test. Taste acuity was determined by recognition-thresholds-for-salt (RTS) using 10 different salt concentrations. Low PZ (<0.7 mg/l) and EZ (<8 µg/g of packed cells) were observed in 72% and 23.6% of girls, respectively. PZ and EZ were negatively associated with SRT (r = -0.41, -0.34), RRT (r = -0.49, -0.4), and positively with Memory (r = 0.43, 0.34) and RPM (r = 0.39, 0.31; p < 0.05) and remained significant after adjusting for socio-demographic factors and hemoglobin. RTS was impaired in 18.3% girls and significantly correlated with EZ (r = -0.31, p < 0.05). Zinc deficiency in adolescent girls was associated with poor cognition and taste function implying need for improving their dietary zinc intakes.

Albumin-normalized serum zinc: a clinically useful parameter for detecting taste impairment in patients undergoing dialysis.

Patients with renal failure often experience decreased serum zinc that remains uncorrected after dialysis. A complication of this depletion is taste impairment, which can detrimentally influence diet and nutrition. However, because more than half of all serum zinc is bound to albumin, we hypothesized that normalizing serum zinc to albumin levels may be associated with taste impairment. A total of 65 patients undergoing dialysis but not receiving supplementary zinc and 120 control patients not undergoing dialysis (60 malnourished patients and 60 healthy controls) were tested for their receptiveness to saltiness using various salt concentrations. Patients' total protein and albumin levels were measured, and linear regressions were extrapolated between serum zinc levels and total protein or albumin. Patients undergoing dialysis had significantly lower levels of total serum zinc compared with control patients. However, uncorrected zinc levels were not correlated with taste impairment. Normalizing zinc levels against total protein or albumin resulted in extrapolated equations that revealed a significant correlation with taste impairment. Our data suggest a statistical correlation between zinc and albumin in both healthy subjects and patients undergoing maintenance hemodialysis, or protein-energy malnutrition without hemodialysis, allowing for a quantitative measure for taste impairment.

Examination of the taste disorder associated with gynecological cancer chemotherapy.

OBJECTIVE: Taste disturbance is known to occur as one of the adverse events associated with chemotherapy for gynecological cancer, but few studies have attempted to assess it in practical terms. Therefore, a range of taste tests was performed in gynecological cancer patients. METHODS: The patients were 23 women with gynecological cancer being treated with anticancer agents. Subjective symptoms of altered taste were classified, and objective findings were obtained with the following four gustatory tests: serum trace element (zinc, copper, iron) levels, tongue cultures, electrogustometry, and the filter paper disc tests. RESULTS: Of the 23 subjects, 11 perceived taste disturbances. The serum zinc level was consistently below the lower limit of normal. On tongue cultures, indigenous bacteria were seen in all patients during the entire treatment period. Electrogustometry revealed a tendency for the development of hypogeusia in the chorda tympani nerve field. Conversely, hypergeusia tended to develop gradually in the greater petrosal nerve field. The filter paper disc test revealed a tendency for the development of hypergeusia for sweetness, saltiness, and sourness in the chorda tympani nerve field. Hypogeusia for bitterness tended to develop with increasing number of chemotherapy cycles. The glossopharyngeal nerve field exhibited the same tendencies as observed in the chorda tympani nerve field. In the greater petrosal nerve field, there was a tendency for the development of hypergeusia for sweetness, sourness, and bitterness. CONCLUSIONS: Abnormal test results were seen in half of patients after cancer chemotherapy.

The role of zinc in the treatment of taste disorders.

In the 1990s the number of patients diagnosed with taste disorders in the USA and Japan was over one million people each year, and the number is increasing annually. Taste disorders are caused by several factors such as genetic disease, head trauma, structural changes, glossodynia, cancer, change of lifestyle, and more. The role of zinc in the treatment of taste disorders has been studied since the oral administration of zinc by patients was reported to improve their taste disorders. Carbonic anhydrase (CA), a zinc metalloenzyme, has also been studied in association with taste disorders, since the regulation of serum CA levels was shown to influence the effect of orally administrated zinc in the treatment of taste disorders. Zinc is an essential trace element that contributes to the active center of approximately 300 enzymes. Studies have revealed that zinc is involved in various physiological functions. Moreover, some medications have been shown to induce a zinc deficiency, which has been associated with a variety of clinical conditions. Hence, since the relationship between taste disorder and serum zinc concentration has been discussed for long time, taste disorder may be useful in diagnosing zinc deficiency. Moreover, it appears that medicines of the zinc-containing supplement type contribute to the treatment of taste disorders caused by zinc deficiency. Orally administered zinc has been shown to directly stimulate food intake via neuropeptide in the hypothalamus. Therefore, zinc administration may potentially be used to treat taste disorders, as well as several other diseases by stimulating feeding. The article presents some promising patents on the role of zinc in the treatment of taste disorders.

[Examination of taste threshold and serum zinc level change after chemotherapy].

For cancer patients undergoing chemotherapy, there is an onset of a variety of adverse events related to treatment. Among the adverse events at the moment is taste disorder, for which there is no established effective supportive care. We report the measurement and study their relationship across the changes in serum zinc and changes in the taste of patients undergoing chemotherapy. For cancer patients undergoing chemotherapy, taste threshold and serum zinc levels were measured on the day before administration of the therapeutic anti-cancer agent, and after administration of anticancer drugs on day 4 and day 7. Of taste thresholds in the test results, the threshold was salty on day 4 and day 7 after administration of anticancer agents, and a significant difference was found on day 7 after treatment with anticancer drugs on a day prior to administration of anticancer agents on day 1 (p<0. 001, p=0. 007), respectively. The serum zinc level was measured. There was no significant difference on day 7 after administration of anticancer agents and anti-cancer agent before administration on day 1 and day 7 after administration of anticancer drugs on day 4(p<0. 001, p<0. 05), respectively. A negative correlation was shown between the "salt of the fourth day threshold" and "serum zinc levels" (r=-0. 418, p

Carbonic anhydrase I, II, and VI, blood plasma, erythrocyte and saliva zinc and copper increase after repetitive transcranial magnetic stimulation.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been used to treat symptoms from many disorders; biochemical changes occurred with this treatment. Preliminary studies with rTMS in patients with taste and smell dysfunction improved sensory function and increased salivary carbonic anhydrase (CA) VI and erythrocyte CA I, II. To obtain more information about these changes after rTMS, we measured changes in several CA enzymes, proteins, and trace metals in their blood plasma, erythrocytes, and saliva. METHODS: Ninety-three patients with taste and smell dysfunction were studied before and after rTMS in an open clinical trial. Before and after rTMS, we measured erythrocyte CA I, II and salivary CA VI, zinc and copper in parotid saliva, blood plasma, and erythrocytes, and appearance of novel salivary proteins by using mass spectrometry. RESULTS: After rTMS, CA I, II and CA VI activity and zinc and copper in saliva, plasma, and erythrocytes increased with significant sensory benefit. Novel salivary proteins were induced at an m/z value of 21.5K with a repetitive pattern at intervals of 5K m/z. CONCLUSIONS: rTMS induced biochemical changes in specific enzymatic activities, trace metal concentrations, and induction of novel salivary proteins, with sensory improvement in patients with taste and smell dysfunction. Because patients with several neurologic disorders exhibit taste and smell dysfunction, including Parkinson disease, Alzheimer disease, and multiple sclerosis, and because rTMS improved their clinical symptoms, the biochemical changes we observed may be relevant not only in our patients with taste and smell dysfunction but also in patients with neurologic disorders with these sensory abnormalities.

A zinc-containing compound, Polaprezinc, is effective for patients with taste disorders: randomized, double-blind, placebo-controlled, multi-center study.

CONCLUSIONS: The effect of a zinc-containing compound, Polaprezinc, was shown to clinically improve the disease conditions of idiopathic taste disorders with no serious side effects in a well controlled double-blinded clinical study. OBJECTIVES: The purpose of the present study was to evaluate the efficacy and safety of a zinc-containing compound in the treatment of patients with idiopathic taste disorders, including patients with low serum zinc, by a Good Clinical Practice (GCP)-compliant, randomized, placebo-controlled, double-blind, multi-center clinical study. SUBJECTS AND METHODS: A group of 109 patients suffering from taste disorders was assigned into placebo and three treatment groups. Each group of patients was given either placebo (n=28), or 17 mg (n=27), 34 mg (n=26) or 68 mg (n=28) of oral zinc, Polaprezinc preparations, daily for 12 weeks. RESULTS: The group of patients given 68 mg zinc showed a significant improvement in their gustatory sensitivity compared with the placebo group. The most common side effects observed were increase in serum triglyceride and serum alkaline phosphatase, decrease in serum iron, and some gastrointestinal incidents, although they were not serious.

[Involvement of zinc in taste disturbance occurring during treatment for malignant tumor in the chest and the effects of polaprezinc oral disintegrating tablets (a retrospective study)].

We analyzed the correlation between serum zinc levels and taste disturbance, and between patient backgrounds and serum zinc levels or taste disturbance, and evaluated the effects of polaprezinc oral disintegrating tablets on taste disturbance in 29 patients with lung cancer and one patient with malignant pleural mesothelioma who were receiving chemotherapy. Taste disturbance developed in 11 (36.7%) out of 30 patients. Serum zinc levels significantly correlated with taste disturbance (p=0.0227). Serum zinc levels were significantly lower (p=0.0235) and taste disturbance tended to be more frequent (p=0.0625) in males. Polaprezinc improved taste disturbance in 5 of 8 patients.

Leukemia case in patient with taste dysfunction.

A blood examination was carried out in order to assess the serum zinc level in a patient with taste dysfunction. A blood cell count was also performed simultaneously and promyelocytic leukemia was identified. This case provides an example of leukemia being detected at the time of a blood test being given to assess taste dysfunction.