ORIGINAL ARTICLE

Influence of cancer and acute inflammatory disease on tasteperception: a clinical pilot study

P. Schalk1& M. Kohl2 & H. J. Herrmann1

& R. Schwappacher1 & M. E. Rimmele1 &

A. Buettner3 & J. Siebler4 & M. F. Neurath4& Y. Zopf1

Received: 10 July 2017 /Accepted: 11 September 2017 /Published online: 25 September 2017# The Author(s) 2017. This article is an open access publication

AbstractPurpose Cancer patients are at high risk of malnutrition andtumor cachexia further increasing morbidity and mortality.Reasons for cachexia are not clear yet, but inflammatory pro-cesses as well as the occurrence of taste disorders reducingnutrient uptake are discussed to play key roles. The purpose ofthis study was to gain insight into causative factors of tastedisturbance in cancer patients. Does the cancer itself, inflam-matory processes or cancer therapy influence taste disorders?Methods To capture an underlying taste disorder patients withcancer (n = 42), acutely hospitalized inflammatory diseasepatients (n = 57) and healthy controls (n = 39) were examined.To assess the influence of chemotherapy, patients with andwithout chemotherapy were compared. Taste tests were per-formed according to DIN ISO 3972:2011. Inflammation wasrecorded using laboratory parameters. Statistical evaluationwas conducted using the Software R.Results Cancer patients showed significantly increased tastethresholds for sweet, salty, and umami compared to healthycontrols. There were no significant differences in taste detec-tion and recognition between patients with former, current, or

without chemotherapeutical treatment. Patients with an acuteinflammatory disease showed an increased taste threshold forumami compared to healthy controls.Conclusions It could be shown that cancer patients sufferf rom tas te disorders i r respect ive of an exis t ingchemotherapeutical treatment. Cancer-related inflammationappears to have a greater impact on taste perception than anacute inflammatory process. Therefore, an adapted dietary ad-justment should be carried out at an early stage for cancerpatients in order to avoid nutritional disorders caused by ataste disorder.

Keywords Cancer . Taste disturbance . Inflammatorydisease . Cachexia . Malnutrition

Introduction

In the course of malignant and acute inflammatory diseases, abroad range of physical functions is affected, frequently lead-ing to reduced food intake and to significant weight loss [1, 2].The resulting unintended reduction of fat and muscle mass canadversely influence prognosis, morbidity, and mortality of thepatients [3]. Impaired nutrient intake is caused by multiplefactors; one of them is altered taste perception [4–6].

Many different factors can trigger taste disorder. For in-stance, benign acute diseases like gastrointestinal or inflam-matory processes can lead to an impaired sense of taste [7].This link has already been described by Zopf et al. in patientswith inflammatory bowel disease who had a significantly in-ferior sense of taste than healthy controls [8].

Due to the underlying disease and the tumor-specific ther-apy, cancer patients often suffer from anorexia. The resultingmalnutrition contributes to the progression of cancer cachexiaand to a reduced quality of life of the patients [9–11]. Systemic

* Y. Zopfyurdaguel.zopf@uk-erlangen.de

1 Hector Center for Nutrition, Exercise and Sports, Department ofMedicine 1, Friedrich-Alexander-University Erlangen-Nuremberg,Ulmenweg 18, D-, 91054 Erlangen, Germany

2 Department of Medical and Life Sciences, Furtwangen University,Jakob-Kienzle-Str. 17, D-78054, VS-Schwenningen, Germany

3 Department of Chemistry and Pharmacy, Emil Fischer Centre,Friedrich-Alexander-Universität Erlangen-Nuremberg, Henkestr. 9,D-91054 Erlangen, Germany

4 Department of Medicine 1, Friedrich-Alexander-UniversityErlangen-Nuremberg, Ulmenweg 18, D-, 91054 Erlangen, Germany

Support Care Cancer (2018) 26:843–851DOI 10.1007/s00520-017-3898-y

inflammation, enhanced catabolic processes [2, 12], and treat-ment with cytostatics or radiation therapy are discussed toinfluence taste sensation [13–15]. Mucosal damage due tothe anti-cancer therapy is supposed to be one reason for theloss of taste, since healing of the mucosal inflammation hasbeen described to improve taste perception [16, 17]. It is notyet clear, however, whether the underlying tumor disease orthe specific therapy is mainly responsible for the taste disor-der. Due to a high variability in the methods used for tastedetection, the results from investigations with patients on im-paired taste sense are hard to compare [18]. There is a partic-ular lack of studies analyzing the taste detection of cancerpatients versus patients with acute benign inflammatory dis-orders. Also missing are studies comparing cancer patientswith or without chemotherapy. Of special interest is the eval-uation of the impact of influence of a systemic inflammationon taste perceptions versus the impact of an acute mucosaldamage due to tumor-specific therapy.

The aim of the presented study was to gain insight into howcancer disease and acute benign inflammatory disorders affecttaste perception. Moreover, we aimed to achieve further infor-mation on a potential impact of chemotherapeutic treatmenton gustatory sensation, in order to improve future therapyrecommendations.

Material and methods

Selection of patients

In order to detect taste perceptions and assess causal factors,the following three groups were compared: tumor patients,acutely hospitalized patients with non-malignant inflammato-ry diseases, and healthy control study participants. The acqui-sition of patients took place in the in- and outpatient care of theDepartment of Medicine 1 of the University HospitalErlangen. Healthy control participants were recruited fromclinical staff and their circle of acquaintances.

Excludedwere persons < 18 years of age, pregnant women,patients suffering fromCOPD (chronic obstructive pulmonarydisease), taking anti-cholinergic medication or taking medica-tion with a known strong influence on taste perception, as wellas patients on parenteral nutrition. Also excluded were per-sons with a known taste or olfactory disorder.

Patient data

The collected data comprise demographic data (age and gen-der), anamnesis data (underlying diseases, drug intake, knowntaste or olfactory disorders, and nicotine or alcohol consump-tion), inflammation parameters (C-reactive protein (CRP),pathological > 5 mg/l, and leukocytes, pathological < 4.0 or> 10.0 × 103/μl) and albumin (pathological < 35 g/l). All

patients’ assessments were performed within 2 days to guar-antee coherence of taste test results with inflammation status.

Taste sensation test

The study participants were asked to refrain from eating,smoking, or drinking prior to testing. The taste sense wastested with a Bwhole mouth method^ using a pump-actionspray [19] with associated pharyngeal adapters. Using thisapproach, we determined the detection and recognition thresh-olds of the five basic taste-producing substances-herein desig-nated as Btastants^ -sweet, sour, salty, bitter, and umami [20,21].

Preparation of solutions

The tastant solutions were prepared in the Aroma ResearchGroup at the University of Erlangen-Nuremberg. The tastantswere solubilized in water, and sorbic acid was added as apreservative. Sorbic acid is anti-microbial, has no influenceon the organoleptic impact, and is soluble in water [22]. Thesolutions analyzed in the taste tests contained 0.1% sorbicacid. Additionally, the stock solution was boiled twice to min-imize microbial contamination. The solutions were also testedregarding their stability in the Institute for ClinicalMicrobiology of the University Hospital Erlangen. The sameconcentrations of the tastant solutions were tested throughoutthe study. The solutions were kept at 2 to 10 °C in the refrig-erator. Prior to each test, all participants received a new set ofpharyngeal adapters for hygienic reasons. The solutions werebased on the standard BSensory analysis to determine tastesensitivity^ (DIN ISO 3972:2011), which had been developedto monitor the taste sensation of study participants [23]. Whilekeeping the concentration steps as described below, the testsolutions were adapted to the elder and hospitalized studycollective by increasing the starting concentration. Thetastants sweet, salty, and umami were tested in six concentra-tion steps. The tastants bitter and sour were tested in sevenbecause pre-tests had shown that six steps were not sufficient.The highest concentrations contained 1.45 g/l citric acid,0.65 g/l caffeine, 5.83 g/l sodium chloride, 55.56 g/l saccha-rose, and 2.92 g/l monosodium glutamate monohydrate.Sodium chloride-, caffeine- and citric acid solutions were sta-ble for more than a week. Nevertheless, all solutions wereprepared freshly every 5 days.

Performance of taste tests

When conducting the taste tests, the tastant solutions werepresented in a standardized sequence. The study participantsreceived water with the same frequency as the tastant solu-tions. The tastant solutions were offered in increasing concen-trations. Umami was presented at the end in order to avoid a

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possibly intensified taste of subsequent flavors [24]. Beforethe exact tastant can be recognized (recognition threshold), ataste is detected (detection threshold) [25]. The concentrationswere raised until a tastant could be determined correctly twicein a row (ascending method of limits) [26]. The quality of thetastants were established by a forced-choice procedure, theseven options being sweet, sour, salty, bitter, umami, or neu-tral and Bother than water,^ or Bno neutral^ tastant.

One puff of the pump spray equated to 75 μl of solution.Generally, two to three puffs were given per tastant solution inorder to apply sufficient amounts of the respective tastant.

The following comparisons were performed to achieve fur-ther insights into taste perception of cancer patients:

1. Patients who received chemotherapeutics during the studycourse were compared to patients, who were currently nottreated with chemotherapeutics.

2. Patients who were treated with chemotherapeutics in thepast (current included) were compared to patients whowere chemotherapy-naïve.

Olfactory test

With every participant, an olfactory analysis using BurghartSniffin’ Sticks was performed to test for hyposmia.

Statistical evaluation

The Software R was used for statistical evaluation [27]. Forpatient characteristics, the One-way ANOVA according toWelch and the Fisher’s exact test were deployed. The data oftaste detection were described as ordinal. Groups were there-fore compared using the Kruskal-Wallis test (One-wayANOVA on ranks). In addition, the Wilcoxon-MannWhitney was applied as post hoc test to compare the groupsby pairs. When applying the post hoc tests, an adjustment ofp values according to Holm-Bonferroni was performed in or-der to avoid type I errors. A p value or adjusted p value < 0.05was defined as significant.

Results

Patient characteristics

In total, 138 patients participated in the investigation with amean age of 65.2 years. The first group consisted of 42 tumorpatients (14 female, 28 male), who were hospitalized due tothe cancer disease (n = 22) or were summoned for tumor-specific chemotherapy (n = 20). Thirty-one of the tumor pa-tients had chemotherapy already in the past; 26 had currentchemotherapy. The second group included 57 patients (25

females, 32 males) who were hospitalized due to an acuteinflammatory disease without malignant underlying diseases.The third group comprised 39 healthy study participants (21females, 18 males). Mean age and gender did not differ sig-nificantly between groups.

Four patients dropped out of the olfactory and taste tests ontheir own request. One of the acutely hospitalized patients hadfood intolerance for glutamate and was therefore excludedfrom the umami testing.

The tumor entities were mostly gastrointestinal tumors(85.3%), with colorectal (33.3%), cholangiocellular (11.9%),pancreatic (11.9%), esophageal (11.9%), stomach (7.1%), orhepatocellular carcinoma (7.1%). 16.7% of the tumor patientssuffered from other cancer types (mamma (4.8%), prostate(4.8%), lung (2.4%), neuroendocrine carcinoma (2.4%), andmalignant insulinoma (2.4%). The patients with acute inflam-matory diseases were hospitalized due to gastrointestinal(66.7%), cardiopulmonary (14%), nephrological (7%), or un-specified inflammatory processes (10.5%).

The tumor patients underwent different chemotherapeuticaltreatments (Table 1).

Taste tests

The three study groups were tested and compared regardingtheir detection and recognition thresholds for the five basictastants.

Analyzing the complete collectives, a significantly higherdetection threshold of the tastants sweet (p value(adj.) = 0.004), salty (p value (adj.) = 0.021), and umami (pvalue (adj.) < 0.001) could be detected in the tumor groupversus the healthy control group.

When comparing cancer patients with hospitalized patientssuffering from benign inflammatory disease, a significantlyincreased detection threshold could be shown only in the tu-mor group for the tastants sweet (p value (adj.) = 0.004) andsour (p value (adj.) = 0.039). On the other hand, the hospital-ized patients with inflammatory disease exhibited a higherdetection threshold for umami (p value (adj.) = 0.002) com-pared to the control group (Fig. 1).

The recognition threshold (Fig. 2) was significantly elevat-ed in the tumor group in comparison to the healthy controlgroup for the tastants sweet (p value (adj.) = 0.024), salty (pvalue (adj.) = 0.031), and umami (p value (adj.) = 0.007).

The acutely hospitalized group differed significantly fromthe control group only in the recognition of umami (p value(adj.) < 0.001).

Comparative analysis of the recognition of the othertastants between the three groups showed differences belowsignificance or no difference.

Furthermore, we could not see any significant differencebetween cancer patients who were currently receiving

Support Care Cancer (2018) 26:843–851 845

chemotherapy, who had been treated with chemotherapeuticagents in the past, or who were chemotherapy-naïve (Figs. 3and 4).

If the line number of chemotherapeutic interventions thepatients had previously received was taken into account, nosignificant differences between a first-line therapy and addi-tional therapy lines were determined in the detection thresh-olds (pchemotherapy line (pcli) = 0.561, bitter: pcli = 0.117,

sour: pcli = 0.848, salty: pcli = 0.87, umami: pcli = 0.611).Moreover, there was no difference in the detection thresholdscaused by the number of performed chemotherapy cycles.

Regarding the inflammatory parameters CRP and leuko-cytes, we did not observe an effect on the taste perception ofthe tumor patients.

Lower albumin values, however, significantly increasedthe detection threshold for salty (p value = 0.002115). The

Fig. 1 Detection threshold—comparison of the three groups. c controlgroup, h hospitalized group, t tumor group. p values (Kruskal-Wallis ranksum test): pkw. p values (adjusted by Holm-Bonferroni): pch = controlgroup vs. hospitalized group, pct = control group vs. tumor group, pht =hospitalized group vs. tumor group. 1. Sweet: pkw = 0.00151. c vs. h, c vs.t, h vs. t. p values: pch = 0.985, pct = 0.004, pht = 0.004. Numbers ofsubjects taken into account / n value: nc = 63, nh = 57, nt = 38. 2. Bitter:pkw = 0.492. c vs. h, c vs. t, h vs. t. p values: pch = 0.846, pct = 0.846,pht = 0.846. Numbers of subjects taken into account / n value: nc = 63,

nh = 57, nt = 38. 3. Sour: pkw = 0.0249. c vs. h, c vs. t, h vs. t. p values:pch = 0.103, pct = 0.507, pht = 0.039. Numbers of subjects taken intoaccount / n value: nc = 63, nh = 57, nt = 38. 4. Salty: pkw = 0.02. c vs.h, c vs. t, h vs. t. p values: pch = 0.098, pct = 0.021, pht = 0.243. Numbersof subjects taken into account / n value: nc = 63, nh = 57, nt = 38. 5.Umami: pkw = 0.000216. c vs. h, c vs. t, h vs. t. p values: pch = 0.002,pct < 0.001, pht = 0.150. Numbers of subjects taken into account / n value:nc = 63, nh = 56, nt = 38

Table 1 Chemotherapeutictreatment characteristics Current chemotherapeutic drug regimen Number of patients (n = 26)

FOLFIRI ((FOLinic acid, Fluoruracil (5-FU), IRInotecan) 10

FLOT (Fluoruracil, Leucovorin, Oxaliplatin, doxeTaxel) /Cisplatin 4

FOLFOX (FOLinic acid, Fluoruracil (5-FU), OXaliplatin 2

Cisplatin, Trastuzumab 2

Gemcitabine, Cis-/oxaliplatin 2

Oxaliplatin 1

Cisplatin, Etoposide 1

Oxaliplatin, 5-FU, Leucovorin, Irinotecan 1

Gemcitabine, 5-FU, Leukovoril 1

Capecitabine, Lapatinib 1

Others 1

Monoclonal antibodies (Bevacizumab, Panitumumab, Trastuzumab, Lapatinib) 11

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Fig. 2 Recognition threshold—comparison of the three groups. c controlgroup, h hospitalized group, t tumor group. p values (Kruskal-Wallis ranksum test): pkw. p values (adjusted by Holm-Bonferroni): pch = controlgroup vs. hospitalized group, pct = control group vs. tumor group,pht = hospitalized group vs. tumor group. 1. Sweet: pkw = 0.0505. c vs.h, c vs. t, h vs. t. p values: pch = 0.384, pct = 0.024, pht = 0.384. Numbersof subjects taken into account / n value: nc = 39, nh = 57, nt = 38. 2. Bitter:pkw = 0.594. c vs. h, c vs. t, h vs. t. p values: pch = 1.0, pct = 1.0, pht = 1.0.Numbers of subjects taken into account / n value: nc = 39, nh = 57, nt = 38.

3. Sour: pkw = 0.754. c vs. h, c vs. t, h vs. t. p values: pch = 1.0, pct = 1.0,pht = 1.0. Numbers of subjects taken into account / n value: nc = 39,nh = 57, nt = 38. 4. Salty: pkw = 0.0432. c vs. h, c vs. t, h vs. t.p values: pch = 0.243, pct = 0.031, pht = 0.278. Numbers of subjectstaken into account / n value: nc = 39, nh = 57, nt = 38. 5. Umami:pkw = 0.000148. c vs. h, c vs. t, h vs. t. p values: pch < 0.001,pct = 0.007, pht = 0.272. Numbers of subjects taken into account / nvalue: nc = 39, nh = 56, nt = 38

a b

Fig. 3 Detection thresholds. (a) Influence of current chemotherapeuticaltreatment. Detection thresholds of patients receiving currentchemotherapy vs. patients currently not receiving chemotherapy. cccurrent chemotherapy, ncc no current chemotherapy. n value: ncc = 24,nncc = 14. Wilcoxon-Mann-Whitney test: Significance levels: 1. Sweet:pcc/ncc = 0.238,W = 129. 2. Bitter: pcc/ncc = 0.814,W = 160. 3. Sour: pcc/ncc = 0.643,W = 152.5. 4. Salty: pcc/ncc = 0.454,W = 193. 5. Umami: pcc/

ncc = 0.701, W = 155. (b) Influence of chemotherapeutical treatment.Detection threshold of chemotherapeutically treated patients vs. chemo-therapy-naïve patients. c chemotherapy, nc no chemotherapy (chemother-apy-naïve). n value: nc = 28, nnc = 10. Wilcoxon-Mann-Whitney test:Significance levels: 1. Sweet: pc/nc = 0,151,W = 97. Bitter: pc/nc = 0.941,W = 137.5. Sour: p

c/nc= 0.81, W = 147.5. Salty: pc/nc = 0.602, W = 156.

Umami: pc/nc = 0.581, W = 123

Support Care Cancer (2018) 26:843–851 847

median detection threshold ± [interquartile range] was 4 [2](low albumin, < 35 [g/l], (n = 9)) and 3 [1] (normal albumin,> 35 [g/l], (n = 17)).

Regarding the other tastants, there were no differences indetection or recognition thresholds.

Olfactory test

The study participants did not show relevant olfactory or smelldisturbance effects.

Discussion

The objective of this study was to examine the influence ofcancer and inflammatory disease on the taste perception ofpatients. Primarily, we demonstrated that the incidence of tastedisturbance is elevated in cancer patients. Hence, we wereinterested to identify triggering factors for this taste distur-bance. Is the tumor therapy the sole reason for taste perceptionimpairment or is the underlying disease partly involved?Therefore, we compared the taste sense of cancer patientsundergoing chemotherapeutical treatment with the taste senseof patients without chemotherapy.

For the first time, we could demonstrate that the taste dis-turbance in cancer patients might not only be dependent onchemotherapeutical treatment. We determined no significant

d i f f e r enc e s be tween pa t i en t s w i t h o r w i t hou tchemotherapeutical treatment. In addition, the number of per-formed treatment lines and cycles of chemotherapy did notsignificantly influence taste perception.

However, cancer patients and hospitalized patients withinflammatory disease showed a disturbed taste perceptioncompared to healthy controls. Comparing acutely hospitalizedand tumor patients with healthy controls, umami was signifi-cantly less perceived in both patient groups (detection andrecognition thresholds). Cancer patients also had higher detec-tion and recognition thresholds for sweet and salty thanhealthy controls. Regarding the tastants sweet and sour, thetaste disturbances in cancer patients compared to hospitalizedpatients were also significantly more pronounced. Similar cor-relations have not been described before, since a comparativeanalysis of tumor patients and acutely hospitalized patientswith inflammatory diseases has never been performed.

Interestingly, the inflammatory status as recorded withCRP values and the leukocyte count had no influence on tastedisturbance (Table 2). Instead, tumor patients with reducedalbumin values exhibited a diminished detection for salty.

The reason why the detection and recognition of sour andbitter did not differ significantly between cancer patients andhealthy controls can in part be explained by our finding thatthe thresholds for these two tastants are generally high in allgroups. For future studies, it is recommended to examine evenhigher maximal concentrations for these two tastants. In

Influence of current chemotherapeutical treatment Influence of chemotherapeutical treatment a b

Fig. 4 Recogni t ion thresholds. (a ) Inf luence of currentchemotherapeutical treatment. Recognition threshold of patientsreceiving current chemotherapy vs. patients currently not receivingchemotherapy. cc current chemotherapy, ncc no current chemotherapy.n value: ncc = 24, nncc = 14. Wilcoxon-Mann-Whitney test: Significancelevels: 1. Sweet: pcc/ncc = 0.266, W = 131,5. 2. Bitter: pcc/ncc = 0.958,W = 166. 3. Sour: pcc/ncc = 0.661, W = 182.5. 4. Salty: pcc/ncc = 0.687,W = 181.5. 5. Umami: pcc/ncc = 0.922, W = 164.5. (b) Influence of

chemotherapeut ica l t rea tment . Recogni t ion threshold ofchemotherpeutically treated patients vs. chemotherapy-naïve patients. cchemotherapy, nc no chemotherapy (chemotherapy-naïve). n value: n-c = 28, nnc = 10. Wilcoxon-Mann-Whitney test: Significance levels: 1.Sweet: pc/nc = 0.31, W = 109.5. 2. Bitter: pc/nc = 1, W = 139.5. 3. Sour:pc/nc = 0.126, W = 185. 4. Salty: pc/nc = 0.895, W = 144. 5. Umami:pc/nc = 0.786, W = 148.5

848 Support Care Cancer (2018) 26:843–851

contrast to our findings, there is evidence in the literature fordisturbed detection of bitter in cancer patients [14]. Somestudies indicate that bitter taste could potentially be regulatedvia tumor necrosis factor (TNF) signaling pathways. Thus, ahigher concentration of TNF due to inflammatory processesand tumor disease could lead to reduced thresholds for bitter[7].

The fact that there is a taste disturbance in both, cancerpatients and patients with inflammatory disorders, suggeststhat the deterioration of taste perception is due to systemicinflammation. Since cancer-induced inflammatory processesare more complex and more pronounced than the inflamma-tion process in acute benign inflammatory disease, taste dete-rioration is possibly more severe in cancer patients.

It is known that inflammation-related changes in the inter-feron and the toll-like receptor pathway negatively affect therenewal of taste bud cells [28]. Further, lipopolysaccharide(LPS)-induced inflammation leads to a reduced proliferationof taste progenitor cells and shortens the lifespan of taste budcells [29]. Since CRP values and leukocyte count had no im-pact on taste detection, other inflammatory mechanisms arelikely to cause taste disturbances. Since the abovementionedtoll-like receptor pathway is known to affect the course of atumor disease [30], it might also affect taste sensation.However, in the course of a tumor disease, many pro-inflammatory cytokines are released inducing inflammationprocesses that might contribute to taste disturbances bydisrupting various phases of taste cell differentiation ordegradation.

The influence of chemotherapeutics on taste sensation isoften blamed for the reduced dietary intake of cancer patients.Attributed to chemotherapeutics are increased detectionthresholds for sweet, sour, salty, or bitter [18], as well as aconstant perception of a metallic taste [31, 32]. An impairmentof the taste buds by cytotoxic substances and a disturbance ofthe renewal processes of taste bud cells are discussed as pos-sible consequences of chemotherapeutic agents leading totaste disturbances [33, 34].

A remarkable finding of our study is that the taste percep-tion of patients with current or former chemotherapeuticaltreatment did not significantly differ from that of chemother-apy-naïve tumor patients (Figs. 3 and 4).

This means that chemotherapy seems not to have the antic-ipated clinically significant effect on taste, or at least not as

strong as the effect of the tumorous process itself. We con-clude from these data that the massive release of inflammatoryfactors in a cancer disease has probably a more relevant influ-ence on taste perception than drug therapy with chemothera-peutics. This underlines the need for a systematic assessmentof anorexia and weight loss in all cancer patients, regardless ofthe underlying therapy and tumor stage.

We could demonstrate that lower albumin values in tumorpatients increased the detection threshold for salty. These re-sults are supported by data from Lynch et al. showing anassociation between low serum albumin levels, low intake ofsodium and protein, and increase of individual taste alterations[35]. Lowered albumin values originate from decreased syn-thesis in the liver, loss of protein, and malnutrition [36]. Thus,treating malnutrition by replenishing protein and albumin res-ervoirs could potentially improve taste disturbances [37].However, this should be examined in detail in future studies.

The observed increased detection and recognition thresh-olds for umami in the acutely hospitalized as well as the tumorpatients compared to healthy controls are remarkable sinceumami is considered as the signal for nutritious meals orprotein-rich food [38]. The tastant umami develops when veg-etables and meat are cooked or roasted because these process-es release glutamate in food [39]. Foods such as Parmesan,smoked ham, or sundried tomatoes also contain large amountsof monosodium glutamate. As a predictor for the protein in-take of a patient, the testing of glutamate could play an impor-tant role, since for humans umami indicates a nutritious pro-tein source [40]. There might even be a correlation between adecreased umami perception and the reduced meat consump-tion of tumor patients. Since patients suffering from acuteinflammatory diseases or cancer, perceive umami to a lesserextent as important taste modality of roasted or cooked meat,their desire for meat might be reduced as a consequence. Sucha correlation has never been verified in a study. However, it isknown that glutamate has a stimulating effect on appetite andsaliva production [41]. When glutamate is elevated in a meal,the craving for salt and sugar is reduced. Thus, the addition ofglutamate to a dish can not only increase its savory perceptionbut may also contribute to a more healthy nutrition of elderly,ill, and tumor patients [39].

In order to collect data on taste alterations adequately, val-idated testing is inevitable. Established methods to determinetaste senses can be divided into regional and Bwhole mouth

Table 2 Inflammatoryparameters (means ± standarddeviation, Mann-Whitney U test)

Parameter Hospitalized patients (n) Tumor patients (n) Significance p value

CRP [mg/l] 36.93 ± 75.47 (52) 23.01 ± 30.04 (30) 0.363

Leukocytes [10^3/μl] 7.38 ± 2.65 (56) 6.45 ± 2.62 (38) 0.155

Albumin [g/l] – 37.13 ± 5.77 (29) –

n number of patients

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methods^ [42, 43]. Regional methods are applied when tastedisturbances are already established. They allow conclusionsabout the nature of triggers on the neural level [33]. For testsof everyday taste perception, as intended in our study, moregeneral, so called Bwhole-mouth methods^ are suitable. Oneof the well-established Bwhole mouth methods^ is the three-drop forced-choice method from Henkin et al. [42, 44].Another method to detect taste perception in a more generalmanner and easier to apply than regional methods is a methodusing a device to spread tastant solutions around the entiretongue [25].

The DIN ISO 3972:2011 is well suited to standardize thepreparation of tastant test solutions and has been used in otherstudies [9]. We observed that the concentrations for caffeinesolutions could be even higher, since the tumor patients andthe acutely hospitalized patients with inflammatory disease,frequently did not reach the detection thresholds of healthysubjects for bitter (Fig. 2). The application of pump spraysenables a relatively even distribution of tastant solutionsaround the entire tongue thereby avoiding the frequently stren-uous sticking out of the tongue. Sprays have been used alreadyin former screenings and are easy to apply [19].

Prospects

Since taste disturbances appear to have negative effectson appetite, nutrition intake, underlying disease, and onquality of life, early detection and treatment is of greatimportance. A potential approach is the treatment ofprotein malnutrition.

Food enhancement is much needed to treat taste distur-bances before additional problems and complications arise,primarily malnutrition and major weight loss [5, 45]. Thisapplies to tumor patients, acutely ill persons, and patients be-ing malnourished due to other reasons. Besides glutamate,various other flavoring substances could be used to makemeals more palatable to patients. This might increase the per-ception of a meal also through other sensory modalities.

Summary

This study could demonstrate that the capacity of tasting candeteriorate significantly during a tumor disease. This seems tobe due not only to chemotherapeutic treatment but multipleother factors of the disease interacting with each other. Thesefactors include inflammatory reactions, protein metabolismdisturbances, and catabolic processes, which in part also occurin other acute diseases. In conjunction with taste disturbances,these factors can promote the development and maintenanceof malnutrition leading to an impaired prognosis.

Acknowledgements We thank Sarah Vogel for her support in taste testrealization and Yvonne Sauermann for preparation of the tastantsolutions.

Compliance with ethical standards

Ethical approval All participants obtained a detailed description of thetest systems and were enrolled in the study after signing a consent form.The study was approved by the ethics committee of the University ofErlangen and is in accordance with the 1964 Helsinki declaration andits later amendments.

Open Access This article is distributed under the terms of the CreativeCommons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncom-mercial use, distribution, and reproduction in any medium, providedyou give appropriate credit to the original author(s) and the source, pro-vide a link to the Creative Commons license, and indicate if changes weremade.

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