J Nutr Health Aging

Volume 20, Number 10, 2016

MULTIDIMENSIONAL EVALUATION OF ENDOGENOUS

AND HEALTH FACTORS AFFECTING FOOD PREFERENCES, TASTE
AND SMELL PERCEPTION
D. GUIDO1,2, S. PERNA3, M. CARRAI4, R. BARALE4, M. GRASSI1, M. RONDANELLI3
1. University of Pavia, Department of Brain and Behavioral Sciences, Medical and Genomics Statistics Unit, Pavia, Italy; 2. University of Pavia, Department of Public Health,
Experimental and Forensic Medicine, Biostatistics and Clinical Epidemiology Unit, Pavia, Italy; 3. University of Pavia, Department of Public Health, Experimental and Forensic
Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, Pavia, Italy; 4. University of Pisa, Department of Biology, Pisa, Italy.
Corresponding author: Simone Perna, University of Pavia, Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition
Unit, Azienda di Servizi alla Persona, Pavia, Italy, Email: simoneperna@hotmail.it

Abstract: Objective: This study, by taking a holistic approach, investigates the relationships between taste,
smell sensitivity and food preference with prognostic (endogenous and health) factors including age, gender,
genetic taste markers, body mass, cigarette smoking, and number of drugs used. Design: Cross sectional study.
Setting: Northern Italy. Participants: 203 healthy subjects (160 women/43 men; mean age: 58.2±19.8 years)
were examined. Measurements: Individual taste sensitivity was determined by saccharose, sodium chloride,
acetic acid and caffeine solutions and by 6-n-propylthiouracil (PROP) responsiveness test. Olfactory sensitivity
has been assessed by «Sniffin’ Sticks». Four tag Single nucleotide polymorphisms (SNPs) in regions of interest
were genotyped. Factor analysis and multivariate regression were performed for scaling food preferences and
screening prognostic factors, respectively. Results: Increasing age is associated with decreased responsiveness to
NaCl (P=0.001), sweet solutions (P=0.044), and smell perception (P<0.001). Concerning the food preferences,
elderly like the “vegetables” and “fruits” but dislike “spicy” more than younger. Regarding number of drugs
taken, there is a significant negative effect on smell perception (P<0.001). In addition, drugs reduce both the
“vegetables foods” score (P=0.002) and the “milk-product foods” score (P=0.027). With respect to Body Mass
Index (BMI), only a significant effect was shown, on sweet perception (P=0.006). Variation in taste receptor
genes can give rise to differential perception of sweet, acid and bitter tastes. No effect of gender and smoking was
observed. Conclusions: Our study suggested that age, genetic markers, BMI and drugs use are the factors which
affect taste and smell perception and food preferences.

Key words: Taste, smell, food preferences, prognostic factors, genes, aging, sex, smoke, body mass index.

Introduction Within this framework, nutrition is an important element

The study of the role of sensory makers and food preferences
in nutrition is of special interest since the past decade has
witnessed scientific advances in this field. In confirmation
of that, a number of study concerned the identification of
receptors and other key molecules involved in the transduction
mechanisms of taste and smell perceptions (1-9). The
evaluation of age-related changes in taste and smell perception
is particularly intriguing, because taste and smell make food
enjoyable. In that respect, we like the taste of sugar because we
have an absolute requirement for carbohydrates (sugars, etc.).
We get cravings for salt because we must have sodium chloride
(common salt) in our diet. Bitter and sour cause adversities
and avoidance reactions since most poisons are bitter and
battering food becomes sour (acidic). In fact, taste and smell
drive appetite and nutrition, therefore the age-related sensory
decline makes decrease the food intake in people and can
influence the food preferences. Moreover, a reduced sense of
smell is associated with reduced interest in intake of food (10,
11). In addition, subjects with a reduced sense of taste tend to
have a less varied diet and consequently develop micronutrient
deficiencies. Finally, the loss of sense of taste may be caused
by a reduced number of taste buds (12).
Received July 15, 2015
Accepted for publication October 5, 2015
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of health in the population and affects the quality of life.
This underscores the need to develop more positive dietetic
approaches to promote healthy eating behaviors in order
to follow the changes in sense markers and preference, by
preventing nutritional disorders, reduced physical activity and
deficit in body composition (13-15). Knowledge of sense-
related endogenous factors such as gender, age and genetic
markers, health factors such as body mass, smoking, drugs use,
factors, and the management of dynamics induced by them, as
alterations in taste and smell perception, and changes in food
preferences, requires a holistic approach. This matter might
help develop innovative “personalized” dietetic approaches for
maintaining an adequate nutritional status.
Various studies have investigated the specific prognostic
factors associated with reduced perception of taste and smell,
namely age (16-19, 20), gender (17, 19, 21-23), smoking habits
(24-26), drugs used (12), genetic markers (27-34), but the
studies in this field are often contradictory. Another important
question also concerns the association between taster status,
genetic markers and food preferences. The taste of food is
certainly a key component of the preferences. Consumers
report that their food preferences are guided primarily by
taste (35). Moreover, food preference of a population are
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MULTIDIMENSIONAL EVALUATION OF ENDOGENOUS & HEALTH FACTORS

important because they can increase the risk of developing
chronic diseases (36).
The understanding of the actual predictor of age-related
changes in the taste and smell sensation and in food preference
is essential to develop targeted dietary paths.
This study evaluates the relationships of endogenous factors
such as gender, age, and genetic markers, and health factors,
namely body mass, cigarette smoking and drugs use on taste
and smell sensitivity, and food preference.
Materials and methods
Sensory testing
Sensory test was conducted in the sensory laboratories
at Endocrinology and Clinical Nutrition Unit of Azienda di
Servizi alla Persona di Pavia, University of Pavia. For the
threshold test, five concentrations of aqueous solutions of
sucrose, citric acid, caffeine and NaCl were tested, using the
ascending forced-choice trial method, as shown in Table 1, to
find each participant’s detection threshold. All solutions were
presented in identical 35-mL medicine cups, and participants
were instructed to rinse with water before and after tasting the
test solutions.

Subjects Table 1
This was a single-center cross-sectional study. Consecutive The threshold test with five concentrations of aqueous
outpatients, aged between 20-95 years and with Body Mass solutions of NaCl, citric acid, caffeine and sucrose
Index (BMI) between 18-30 kg/m2, who were admitted to
the Endocrinology and Clinical Nutrition Unit of Azienda di Test cups NaCl (mg\ Citric Acid Caffeine Sucrose
Servizi alla Persona di Pavia, University of Pavia (Italy) and ml) (mg\ml) (mg\ml) (mg\ml)
were prospectively enrolled. All subjects had to give complete 1 17.9 12.6 1.4 85.5
medical histories, and all underwent physical examination,
2 35.8 17.9 2.6 137.6
anthropometric assessment and routine laboratory tests.
3 57.6 20.3 4.2 221.4
Figure 1 4 92.7 32.7 6.7 356.3
Flow diagram of the study 5 149.1 43.8 10.0 449.6

Olfactory sensitivity
Olfactory sensitivity was assessed using the 12-item Sniffin’
Sticks olfaction test (Burghart Messtechnik GmbH, Wedel,
Germany). Sniffin’ Sticks (39) are penlike devices filled with
odorants. The cap is simply opened and the patient can sniff at
the tip of the felt. The ‘Screening 12 Test’ is an identification
test with 12 different everyday smells. It can be used to find a
rough answer to the question whether a patient has normal or
diminished olfactory capability. The patient names the smells
using a multiple choice form which offers four definitions for
every pen, only one of which is correct.

Taste Responsiveness to 6-Propylthiouracil (PROP)

Figure 1 shows the flow diagram of the study. Eighty
subjects have been preliminary excluded from the study: fifty-
one refused to participate and twenty-nine had severe cognitive
dysfunction. In addition, subjects with altered glycol and lipid
metabolic control, uncontrolled distyroidism, with mouth
ulcers, affected by severe dysphagia or takening well-known
drugs that reduce the taste and smell (37) were excluded.
Subjects over 65 were eligible if they had the characteristics
shown in Senieur Protocol (38).
The study was performed following approval of the Ethics
Committee of the Department of Internal Medicine and Medical
Therapy, in University of Pavia. Subjects gave their written
consent to the study.
All patients tasted and rated six concentrations of PROP
(Pfaltz and Bauer, Waterbury, CT). The six concentrations
of PROP were 0.05, 0.5, 3.2, 5.5, 16.5 and 55 mmol/L,
respectively. All solutions were prepared at least 1 day before
testing and were stored at 20° C. A dose of 1 ml of solution was
fractionated on a wafer of absorbent material. For the threshold
test, each wafer containing PROP was placed on the tongue,
until the detection of the taste.
Food preferences questionnaire
Participants were administered a food preference
questionnaire, proposed by Catanzaro et al. (40), consisting
of 27 items structured on 5-point scale (1 = ‘‘I hate it’’ to 5
= ‘‘I love it’’). Food preferences were chosen to provide a
comprehensive but non redundant representation of the Italian

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diet. Dietician submitted questionnaire after taste and smell
assessment, and participants were asked not to discuss their
food preferences while completing the questionnaire.
Genetic Markers
Tag Single nucleotide polymorphisms (SNPs) in genes
likely to be involved in the human sweet and bitter taste
receptor system were selected with the use of the Tagger
program within Haploview software (41, 42). The resulting
SNPs captured genetic variability in four chromosome regions
of interest as previously suggested (43-45), namely rs713598 in
the TAS2R38 gene, and rs7792845 (near the gene GNAT3) on
chromosome 7, rs7903146 (TCF7l2 gene) on chromosome 10,
and rs2274333 (CA6 gene) on chromosome 1.
Deoxyribo Nucleic Acid (DNA) was extracted from buccal
swab following the Invisorb® Spin Swab KitIl protocol. The
Invisorb® Spin Swab Kits simple procedure which comprises
following steps: lysis of cells with standard proteinase K,
binding the genomic DNA to the membrane of a Spin Filter,
washing membrane with elimination of ethanol, and then
elution of genomic DNA. All genotyping were carried out
using Kaspar (Kbioscience, Heddesdon, UK) assay PCR plates
and they were read on a ViiA 7 RUO Software, instrument
(Applied Biosystems).
Food preferences scaling
We analyzed the “food preferences” questionnaire by
Factor Analysis with R software (v. 3.0.3: package psych
v.1.4.8.11) (46). Firstly, we used exploratory factor analysis
(EFA) to investigate a food preference patterns. Secondly, we
used confirmatory factor analysis (CFA) to validate the factor
structure provided by EFA.
EFA was performed on the polychoric correlation
matrix of the 27 ordinal (5-point) food preference items. To
determine the number of factors to be retained, we considered
a combination of criteria: factor eigenvalues greater than
1, screeplot inspection, Horn’s Parallel Analysis (47) and
Velicer’s Minimum Average Partial (MAP) criterion (48),
looking for the optimal number of factors to retain at the curve
break point, and factor interpretability (49). We applied a non-
orthogonal (oblimin) rotation to the factor loading matrix to
obtain a simpler structure and improve interpretability. The
derived “food preference” patterns were quantitatively labeled
according to those item that loaded mainly on the respective
factors (50).
CFA was performed on the polychoric correlation matrix
to validate the overall factor structure obtained by EFA. CFA
parameters were estimates by diagonally weighted least square
(DWLS) method. Goodness-of-fit indices, i.e. comparative fit
index (CFI) and Tucker-Lewis index (TLI)bigger than 0.9 were
considered for an “adequate approximation” fitting of the CFA
model to data. For each factor, indices of unidimensionality
(AVE=average of items variance extracted by construct) (51),
reliability (52) (omega=ratio of variance of the construct
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scores to the scale scores) (52), and construct validity (52)
(rho=correlation of scale scores with construct scores) (52)
were computed to validate the factors. In addition, an item-
factor correlation, i.e. (confirmatory) factor loading (>0.4),
proved high-quality specific validity for each item of the factor.
Last, the continuous factor scores rescaled in preference units
(from 1 to 5), that measures the subject’s food preference
underline to the identified factors, were used for multivariate
analysis.
Multivariate regression analysis
In order to analyze the effects of different endogenous
and health factors (i.e. explanatory variables) on taste and
smell perception and food preference factors returned by
factor analysis (i.e. the outcome variables), we performed
a multivariate multiple regression model (MRA) with R
software (v. 3.0.3) and its package lavaan (v. 0.5.17) (53).
In the response variables set there are PROP concentration,
responsiveness to solutions (NaCl, citric acid, caffeine
and sucrose), the olfactory sensitivity test and the “food
preferences” factor scores obtained from CFA. The explanatory
variable set include: gender, age, BMI, cigarettes smoking
habit (Yes/No), number of drugs, and the genetic markers
(SNPs, additively recoded as 0,1,2), adjusted for a proxy frailty
variable measured by the Charlson Comorbidity Score (without
age score) (54). The residuals of outcome variables are all
correlated, as expected from the model. The effects of the
explanatory variables on the outcome variables (i.e. regression
coefficients=β) are conditional, e.g. expected outcome variation
per unit increase of explanatory variable, keeping fixed the
others in the built-in model, while the residual associations
of the outcome variables (i.e. correlation coefficients=ρ) are
interpreted as marginal pairwise correlations without fixing the
others in the built-in model.
In order to evaluate statistical significance on model
parameters, we carried out z-tests (null hypothesis, H0: β=0 and
H0: ρ=0) with a two-sided P-value<0.05 considered statistically
significant. Huber-White robust standard error were used to
manage non-normality joint distribution.
Results
Subjects
Two hundred and three subjects (160 women and 43 men)
have been evaluated. Concerning the most frequently employed
drugs, 29% of patients were receiving heparin, 22% drugs for
the treatment of osteoporosis (bisphosphonates or denosumab).
The phenotypic and genotypic characteristics of the subjects
are shown in Table 2.
Food Preferences Scaling
The EFA statistics, i.e. eigenvalue >1, Valicer’s MAP=0.02
and Horn’s parallel analysis identified four factors. Table 3
shows the factor loading matrix for the four retained factors
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Table 2
Descriptive statistics of the sample

Women (n=160) Men (n=43) Total (n=203)

Endogenous factors
Age (y), mean ± s.d. 57.9 ± 20.3 59.6 ± 17.8 58.2± 19.8
rs713598 (0=CC / 1=CG / 2=GG) 36/81/43 4/25/14 40/106/57
rs7903146 (0=TT / 1= TC / 2= CC) 21/83/56 7/19/17 28/102/73
rs2274333 (0=GG / 1=GA / 2=AA) 13/82/65 1/27/15 14/109/80
rs7792845 (0=GG/ 1=GA / 2=AA) 43/88/29 19/17/7 62/105/36
Health factors
Body Mass Index, mean ± s.d. 26.4 ± 5.59 27.7 ± 5.72 26.7 ± 5.63
Cigarette smoking habit (Yes/No) 33/127 6/37 39/164
No. drugs, mean ± s.d. 2.36 ± 2.82 2.70 ± 2.85 2.43 ± 2.82
Charlson Comorbidity Score, mean ± s.d. 2.61 ± 2.80 2.72 ± 2.46 2.63 ± 2.73
Outcome variables
Responsiveness to PROP concentration (mmol/L), mean ± s.d. 8.81 ± 14.3 14.6 ± 18.9 10.0 ± 15.5
Responsiveness to NaCl solution (mg\ml), mean ± s.d. 31.6 ± 18.5 33.5 ± 15.4 32.0 ± 17.8
Responsiveness to citric acid solution (mg\ml), mean ± s.d. 14.9 ± 4.78 15.8 ± 5.55 15.1 ± 4.95
Responsiveness to caffeine solution (mg\ml), mean ± s.d. 4.42 ± 2.59 4.94 ± 2.91 4.53 ± 2.66
Responsiveness to sucrose solution (mg\ml), mean ± s.d. 136.5 ± 74.6 123.4 ± 73.8 133.7 ± 74
Olfactory sensitivity (no. wrong responses over 12 items), mean ± s.d. 2.42 ± 2.22 2.82 ± 2.49 2.51 ± 2.28

after the oblimin rotation. The magnitude of each loading
indicates the importance of the corresponding food preference
item to the factor. These factors accounted for about 39% of
the total variance in the original data. The factor structure
was satisfactory, with 13 items having factor loadings (i.e.
item-factor correlations) >0.60, four around 0.50, and six from
0.30 to 0.40. Items with loadings <0.40 (absolute values) were
deleted and excluded from successive CFA. The first factor,
labeled ‘‘vegetable’’ had the greatest loadings on vegetables,
cabbage, artichokes, spinach, garlic, and onion; the second
factor, labeled ‘‘spicy’’ had the greatest loadings on sauces,
ketchup, mustard, chili, and mayonnaise; the third factor,
labeled ‘‘milk products’’ was characterized by the greatest
loadings on fresh cheese, hard cheese, butter, and cream; the
fourth factor, labeled ‘‘fruits’’ had the greatest loadings on
fruits.
Table 4 shows the CFA output for the definitive factors
structure derived by EFA, after deletion of item with
factor loadings < 0.4. Specifically, 17 items over 27 (63%)
of the questionnaire were retained. Overall, fit indices of
CFA (CFI=0.9 and TLI=0.9) were adequate. Indices
of unidimensionality (AVE >0.2) reliability (omega >0.7)
and general factor validity (rho >0.8) for each factor were
satisfactory, and the item-factor correlations (>0.4) proved
high-quality specific factor validity for each food preference
items. We computed the four factor scores (the higher the
scores, the greater the food preferences) interpreted as a
quantitative measure of the preferences to “vegetable foods”,
“spicy foods”, “milk-product foods”, and “fruits foods”, that
we included in the response variable set of next multivariate
regression analysis.
Multivariate regression analysis
In order to achieve a more conservative and interpretable
model, we performed a model selection procedure using a
backward technique where we removed unnecessary
explanatory variables whose regression coefficients returned
P-value>0.1. In this way, smoke habit, gender and one genetic
marker (rs2274333) were deleted from the predictors set. In
particular, because gender coefficient was non significant, the
skewness gender distribution (160 women vs. 43 men) had not
consequences on the selected explanatory variables.
The regression coefficient estimates (effects, β) of the final
multivariate multiple linear regression model are reported in
Table 5: the explanatory variables are reported in rows, and
response variables in columns. All regression coefficients
are interpreted as effects adjusted for all other explanatory
variables include in the model.
Age effects
Age decreases responsiveness to NaCl and sweet solutions,
and smell perception. Specifically, for a 5-year increase of

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Table 3
Exploratory Factor Analysis: standardized loadings (pattern matrix) based upon polychoric correlation matrix
of food preference items

Foods “Vegetable” “Spicy” “Milk-products” “Fruits”

Preferences Factor Preferences Factor Preferences Factor Preferences Factor
Artichokes 0.77 0.01 0.00 0.07
Cabbage 0.75 0.03 -0.08 0.16
Spinach 0.74 -0.01 0.03 0.15
Vegetables 0.68 -0.06 -0.08 0.09
Onion 0.67 -0.04 0.09 -0.19
Garlic 0.63 0.07 0.07 -0.28
Liver 0.32 0.05 0.10 -0.14
Whipped cream -0.32 0.21 0.22 0.03
Sauces -0.03 0.89 -0.10 0.12
Ketchup -0.01 0.83 0.00 -0.03
Mayonnaise -0.12 0.77 0.06 0.05
Mustard 0.14 0.76 0.10 -0.12
Chili 0.23 0.48 0.05 -0.24
Salty snacks 0.12 0.31 0.14 -0.16
Vinegar 0.11 0.31 -0.05 0.13
Balsamic vinegar 0.07 0.25 -0.02 -0.03
Butter -0.05 -0.06 0.84 0.05
Cream 0.01 0.11 0.75 -0.09
Fresh cheese 0.20 -0.03 0.46 0.18
Hard cheese 0.24 -0.10 0.40 0.12
Fruit 0.28 -0.04 -0.03 0.69
Cake -0.31 0.16 0.16 0.52
Citrus fruit 0.33 0.13 -0.01 0.50
Milk chocolates -0.28 0.07 0.16 0.33
Black chocolates 0.01 0.13 -0.03 0.08
Meat -0.01 0.15 0.01 -0.09
Ham, salami etc. 0.04 0.07 0.23 0.03
Proportion of explained variance (%) 0.14 0.12 0.07 0.06
Cumulative explained variance (%) 0.14 0.26 0.33 0.39
Factor loading estimates from an exploratory factor analysis performed on 27 food preferences items. The magnitude of each loading indicates the importance of the corresponding item
to the factor. Loadings greater than 0.40 (in absolute value) are shown in bold.

age, the average responsiveness to NaCl solution decreases of
1.25 mg\ml (P=0.001), the sweet solution decrease of 3.5 mg\
ml (P=0.044) and the olfactory sensitivity decreases, because
the average number of Sniffin’ Sticks errors increases of 0.225
(P<0.001).
Concerning the food preferences, elderly like the
“vegetables” and “fruits” but dislike “spicy” more than younger
subjects. Particularly, for 5-year increase of age, the average
of “vegetables foods” score increase of 0.074 preference units
(p.u.) (P=0.003), as well as “fruits food” score that increased of
0.040 p.u. (P=0.061). Differently, “spicy food” score decreased
of 0.095 p.u. (P<0.001).
Genetic effects
Regarding genetic effects, marker rs713598 is associated
to bitter taste. In fact, this genetic marker has effects both
on PROP concentration and caffeine solution outcome. In
the former, the additional presence of G allele decreases the
PROP responsiveness: the recognition of the taste occurred at
a bigger concentration of 7.13 mg/ml. (P<0.001). Similarly,

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Table 4
Confirmatory Factor Analysis: loadings (item-factor correlations) and indices of the food preferences factors

“FOOD PREFERENCES” FACTORS

“Vegetable” “Spicy” “Milk-products” “Fruits”
Preferences Preferences Preferences Preferences
Factor Factor Factor Factor
Spinach Sauces Cream Citrus fruit
0.79 0.85 0.78 0.76
Artichokes Ketchup Butter Fruit
0.78 0.81 0.77 0.74
Cabbage Mustard Fresh cheese Cake
0.78 0.78 0.51 (removed)
Vegetables Mayonnaise Hard cheese Milk chocolates
0.65 0.78 0.41 (removed)
Onion Chili
0.67 0.50
Garlic Vinegar
0.60 (removed)
Liver Nibbles
(removed) (removed)
Whipped cream
(removed)
AVE 0.51 0.57 0.41 0.57
omega 0.86 0.86 0.72 0.72
rho 0.93 0.93 0.85 0.85
AVE: unidimensionality index; omega: reliability index; rho: factor validity index; Loadings smaller than 0.40 were not shown because the item was removed

but non significantly, responsiveness to caffeine solutions
is 0.436 mg/ml lower (P=0.086). Moreover, also the marker
rs7903146 is linked to PROP concentration test, even if with
C-inverse magnitude: for each additional presence of C allele,
responsiveness occurred at a concentration of 4.04 mg/ml
(P=0.003). Notably, this SNP is suggestively associated with
the responsiveness to sucrose solution: the additional presence
of C allele increase the perception of 12.2 mg/ml (P=0.075).
Last, the marker rs7792845 is linked to sweet and citric
solutions. Both the effects are negative because the additional
presence of A allele decreases the responsiveness by 13.5 mg/
ml (P=0.044) for the sweet solution and 1.227 mg/ml (P=0.021)
for the citric solution. No association of genetic markers with
the food preference scores was observed.
BMI effects
The body composition affects sweet taste and “fruits” score.
For each additional BMI unit (kg/m2) the responsiveness to
sweet solution increases of 2 mg\ml (P=0.006), while “fruits
food” score decreases of 0.017 p.u. (P=0.075); on the other
hand, “milk-products foods” score increased of 0.022 p.u.
(P=0.084). Notably, the last two effects provided only
suggestive significances.
Drug use effects
The number of drugs decreases the olfactory sensitivity:
for each additional unit, the average of smell error numbers
increases of 0.299 (P<0.001). In addition, drugs reduce both the
“vegetables foods” score (-0.111 p.u., P=0.002) and the “milk-
product foods” score (-0.074 p.u, P=0.027), and the “fruits
food” one in suggestive way (-0.058 p.u., P=0.087).
Explained variances and residual correlations
The variability explained of each response variable
by the explanatory variables (Table 6) returned through the
determination coefficients (R2) were, in decreasing order:
42.9% (olfactory sensitivity), 21.1% (sucrose solution), 15.7%
(PROP concentration), 11.8% (“spicy foods” score), 8.0%
(NaCl solution), 7.7% (“vegetables foods” score), 5.9% (citric
acid solution), 5.8% (“milk product” score), 3.5% (“fruits
foods” score) and 2.9% (caffeine solution).
Moreover, the residual correlation (ρ) estimates of the

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Table 5
Regression coefficient estimates (β) of the fitted model (rows=explanatory variables, columns=response variables)

PROP Caffeine Sucrose NaCl Citric acid Olfactory Vegetables Spicy food Milk pro- Fruits
concentration solution solution solution solution sensitivity preferences preferences ducts preferences
score score preferences score
score
Age 0.350 (0.337) -0.115 (0.140) 3.500 (0.044) 1.250 (0.001) 0.015 (0.916) 0.225 0.074 (0.003) -0.095 0.024 (0.345) 0.040 (0.061)
(x5years) [-0.350; 1.100] [-0.265; [0.005; [0.500; [-0.255; (<0.001) [0.028; (<0.001) [-0.024; [-0.006;
0.035] 7.000] 1.950] 0.285] [0.140; 0.121] [-0.141; 0.071] 0.080]
0.315] -0.055]
No. drugs 0.890 (0.222) 0.141 (0.219) 1.000 (0.757) -0.160 0.335 (0.136) 0.299 -0.111 (0.002) -0.005 -0.074 -0.058
[-0.540; 2.310] [-0.084; [-5.100; (0.815) [-0.104; (<0.001) [-0.184; (0.903) (0.027) (0.087)
0.366] 7.000] [-1.480; 0.778] [0.142; -0.040] [-0.084; [-0.138; [-0.124;
1.170] 0.455] 0.074] -0.008] 0.008]
Body Mass 0.010 (0.975) 0.009 (0.742) -2.000 0.140 (0.472) 0.063 (0.262) -0.018 -0.005 0.006 (0.576) 0.022 (0.084) -0.017
Index [-0.440; 0.450] [-0.046; (0.006) [-0.250; [-0.047; (0.435) (0.650) [-0.015; [-0.003; (0.075)
0.065] [-3.400; 0.540] 0.174] [-0.063; [-0.026; 0.028] 0.045] [-0.036;
-0.600] 0.027] 0.017] 0.002]
rs713598 7.130 (<0.001) 0.436 (0.086) 3.600 (0.633) -0.860 -0.623 (0.211) -0.103 -0.016 0.041 (0.656) -0.089 -0.041
[4.260; 10.000] [-0.062; [-11.200; (0.650) [-1.600; (0.581) (0.867) [-0.138; (0.365) (0.584)
0.935] 18.300] [-4.560; 0.354] [-0.467; [-0.205; 0.219] [-0.283; [-0.189;
2.850] 0.262] 0.174] 0.104] 0.107]
rs7903146 4.040 (0.003) 0.283 (0.249) -12.200 0.590 (0.763) 0.576 (0.252) -0.090 -0.137 (0.110) 0.037 (0.698) 0.109 (0.257) 0.001 (0.993)
[1.340; 6.740] [-0.198; (0.075) [-3.270; [-0.408; (0.630) [-0.306; [-0.150; [-0.080; [-0.161;
0.765] [-25.600; 4.460] 1.562] [-0.454; 0.032] -0.223] 0.298] 0.162]
1.200] 0.275]
rs7792845 -0.940 (0.519) 0.104 (0.675) 13.500 -0.550 1.227 (0.021) 0.119 (0.558) 0.062 (0.495) 0.055 (0.579) -0.035 -0.018
[-3.810; 1.920] [-0.384; (0.044) (0.740) [0.180; [-0.279; [-0.115; [-0.138; (0.717) (0.798)
0.593;] [0.300; [-3.780; 2.274] 0.516] 0.239] 0.247] [-0.223; [-0.155;
26.700] 2.690] 0.153] 0.119]
P-values are in round brackets, 95%CIs in square brackets (in bold: P<0.05)

response variables (Table 6) show that PROP residuals are
reversely correlated with “vegetables food” score (-0.153,
P=0.046) and citric acid residuals (-0.095, P=0.047), and they
are positively correlated with olfactory sensitivity residuals
(0.163, P=0.046). In addition, caffeine solution residuals are
positively and consistently correlated with citric acid residuals
(0.235, P=0.011), but they are negatively associated with
sucrose solution residuals (-0.141, P=0.047) and “vegetables
preference” score (-0.140, P=0.085 – suggestive evidence).
Sucrose solution residuals also provided suggestive evidence
of association with olfactory sensitivity (0.166, P=0.076) and
“spicy food” score residuals (0.141, P=0.069). Last, the positive
correlation between “vegetable food” and “fruits” residuals
(0.564, P<0.001), and the correlation between “milk product
food” and “spicy food” residuals (0.289, P<0.001) are worth
noticing.
Discussion
Several considerations could be suggested by the observed
effects of different prognostic factors on food preferences and
taste and smell perception via multivariate multiple regression
model.
Age effects
Responsiveness to NaCl and saccharose solution, and smell
perception significantly decrease with increasing age. As a
consequence, there is a clear decreasing trend for salty taste
perception and olfactory sensitivity. The other taste sensitivity
(citric acid and caffeine solutions) and PROP responsiveness
did not show any significant age-related relationships. These
results are in agreement with Iwamoto et al. 2013, which
stated that a reduced sense of salty is well-known during
normal aging, while the changes of sweet, bitter, and sour
tastes are different among elderly individuals (16). However,
other studies have not confirmed these results (17-19).
Moreover, an age-effect on sweet taste sensitivity has been
found, in line with previous studies (55, 56). A reduced sweet
taste perception may induce elderly people to add excessive
amounts of sugar to their food and beverages and/or prefer
sugar foods and drinks. The possible consequences are poor
adherence to recommended low-sugar diet and a consequently
higher risk of hyperglycemia; the correlation between the
consumption of sugary beverages and systolic and diastolic
blood pressure, might mean a higher risk of hypertension in
normotensive patients and a worsening blood pressure profile
in hypertensive patients (57). Therefore, it is important to
reduce dietary sugar intake to prevent cardiovascular disease
(58). Regarding smell ability, our results are in agreement with
previous cross-sectional studies which suggest that about half

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Table 6
Coefficients of determination (R2) and residual correlations (ρ) of the fitted model

PROP Caffeine Sucrose NaCl Citric acid Olfactory Vegetables Spicy food Milk pro- Fruits
concentration solution solution solution solution sensitivity preferences preferences ducts preferences
score score preferences score
score
PROP 0.157 -0.013 0.001 0.103 -0.095 0.163 -0.153 -0.012 -0.016 -0.003
concentration (<0.001) (0.845) (0.985) (0.100) (0.047) (0.046) (0.046) (0.818) (0.811) (0.965)
Caffeine - 0.029 -0.141 0.103 0.235 -0.079 -0.140 0.058 0.091 -0.037
solution (<0.001) (0.047) (0.152) (0.011) (0.220) (0.085) (0.394) (0.190) (0.585)
Sucrose - - 0.211 0.065 -0.014 0.166 0.040 0.141 -0.008 0.111
solution (<0.001) (0.494) (0.831) (0.076) (0.552) (0.069) (0.892) (0.122)
Nacl solution - - - 0.080 0.068 0.026 -0.087 -0.016 -0.063 -0.070
(<0.001) (0.299) (0.708) (0.303) (0.820) (0.504) (0.419)
Citric acid - - - - 0.059 0.010 0.083 -0.014 -0.016 0.040
solution (<0.001) (0.887) (0.214) (0.866) (0.863) (0.572)
Olfactory - - - - - 0.429 -0.046 -0.034 -0.023 0.041
sensitivity (<0.001) (0.543) (0.703) (0.732) (0.579)
Vegetables - - - - - - 0.077 0.065 -0.006 0.564
preferences (<0.001) (0.371) (0.931) (<0.001)
score
Spicy food - - - - - - - 0.118 0.289 0.117
preferences (<0.001) (<0.001) (0.119)
score
Milk products - - - - - - - - 0.058 0.032
preferences (<0.001) (0.637)
score
Fruits - - - - - - - - - 0.035
preferences (<0.001)
score
R2’s are on the diagonal, residual correlations (ρ) in the upper triangular matrix. P-values are in brackets (in bold: P<0.05).

of the United States population between 65 and 80 years of Gender effects

age has demonstrable smell loss and that, among the subjects
over the age of 80, approximately three-quarters experienced
such loss (60-62). Lower prevalence have been seen in very
healthy cohorts (63, 64) and in some other populations (65,
66), although test methods and criteria for defining dysfunction
vary considerably among studies. These results suggest that
age-related declines in olfaction may occur as a part of the
normal physiological aging process (20 ,67). As described in
recent papers, multiple factors contribute to this age-related
smell loss (20, 68). As shown for the food preferences, we have
demonstrated an effect of age on the choice of vegetables: the
older subject chooses to eat vegetables and dairy products.
Elderly perceive foods differently, and this may influence their
patterns of food consumption, but this topic remains under
study although the issue has been known for a long time (69,
70). Our results are in agreement with the results by Kossioni
et al. which revealed that increasing age was associated with
increased preference for vegetables and dairy products in a
group (71). In addition, we have shown an effect of age on the
choice of sauces: the older subject prefers to avoid sauces. In
summary, people make different food choices as they get older:
most subjects are elderly, more choose with pleasure vegetables
and dairy products and more avoid sauce.
Various studies, although with contradictory results, showed
significant gender differences in taste processing (17, 19,
21-23); however, definite conclusions have not been reached
yet (72). A recent review which considered factors that may
affect olfaction and the ability to perceive smell, reported that
women are superior to men in their ability to identify odours.
(73) Our result indicate that gender difference has no effect on
taste and smell. This discrepancy between a part of literature
and our results may be due to the complex relationships
existing among the functional properties of the human olfactory
system and neuroendocrine factors, in line with the review by
Doty (72).
Genetic effects
We have investigated possible associations between taster
status and four SNPs involved in taste perception. We found
that two tested polymorphisms were associated with taste
perception. For genotypes rs713598 in the TAS2R38 gene and
rs7903146 (TCF7l2 gene), an effect on bitter perception has
been shown; the increase of the G and C alleles corresponds to
a lower sensitivity to the bitter taste. For genotype rs7792845
(near the gene GNAT3), an effect on sweet and acid perception
has been disclosed; the increase of the G allele corresponds
to an increase (responsiveness decrease) of the sensitivity to

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the sweet (responsiveness acid) taste. Our results confirm that
variation in taste receptor genes can give rise to differential
perception of sweet, acid and bitter tastes, as previously
reported (74, 75).
BMI effects
Investigations concerning relationships between taste
perception and obesity have focused mainly on sweet and
bitter tastes. The results of our study suggest that when BMI
increases, the average sweet perception increases. No other
effect of BMI on taste and smell ability has been found. Many
studies have indicated a relationship between taste acuity
for sweet flavors and body mass index - with higher risk of
overweight, obesity and related metabolic and cardiovascular
diseases - but the results are controversial (59). These results
are not in agreement with other studies which demonstrated
that higher BMI is associated with lower perceived sweetness
(76-78), even if the association between body weight and
taste perception, in particular sweet and bitter, has not been
elucidated. (59) The relationship between the PROP taste
phenotypes and obesity has not been observed in our study, but
this relationship is controversial, and some (79, 80), but not all
(70, 81-83) reports, suggested that non-starters have increased
BMI. Previous reports observed that Phenylthiocarbamide
(PTC) tasters tended to be thinner (ectomorphs), whereas
nonstarters tended to have heavier body types (endomorphs)
(84). Other studies in adults (79, 80) and children (84) have
noted moderate-to-weak associations between PROP status
and BMI, suggesting that nontasters may be prone to obesity at
various stages of development. The mechanism linking PROP/
PTC status to body weight is not known, but one suggestion
is that it may influence the discriminability (85, 86) and
palatability (87, 88) of dietary fat.
Smoking effects
This study suggested that the effect of smoking on smell
and taste perception is not statistically significant. Little
is known about the influence of cigarette smoking on the
ability to smell. Our study is in agreement with the research
of Bramerson, conducted on 1387 volunteers in which
logistic regression analysis showed a significant relationship
between impaired olfaction and aging, male gender, and
nasal polyps, but not diabetes or smoking (89). However,
Frye reported a dose-related effects of cigarette smoking
on olfactory function in a group of 638 subjects for whose
detailed smoking histories were available (90). Furthermore,
the study of Katotomichelakis showed that smoking was
adversely associated with the olfactory ability in a dose-related
manner, and also, that smokers had an olfactory deficit six
times greater than non-smokers, depending on the duration
and the amount of cigarettes smoked (91). Regarding the
influence of tobacco smoking on taste sensitivity, the literature
is contradictory. Konstantinidis et al. has shown that taste
function presents significant resistance to smoking, although
changes in morphology of fungiform and filiform papillae have
979
been observed especially in heavy smokers (26). The result
of our study, in agreement with Konstantinidis’s, showed that
the effect of smoking on taste perception was not significant.
However, other studies illustrated that the ability to recognize
four basic types of taste and detection thresholds were lowered
in smokers (24, 25). Probably studies on this topic returned
contradictory findings because a number of them have failed
to take into account smoking dose and duration, and type
of cigarette. Moreover, our study has not evaluate dose and
duration, and type of cigarette dose.
Drug use effects
Our results suggested that for each additional drug, the
average smell error numbers increases. Various studies
showed that the intake of medications adversely affects
the sense of smell in elderly (92), but specifically very few
studies have been performed to evaluate the impact of the
number of medications on the sense of smell (93). Losses
of smell ability in the subjects can reduce appetite and lead
to inadequate dietary intake. Although these chemosensory
deficits are generally not reversible, sensory interventions,
including intensification of taste and odor, can compensate
for perceptual losses. A study illustrated that the flavor and
taste amplification (with MSG, Mono Sodium Glutamate) can
improve food palatability and acceptance, increase salivary
flow and immunity, and reduce oral complaints in both sick and
healthy elderly (93). Flavors increase the number of molecules
that interact with receptors and compensate for chemosensory
losses. Addition of flavors (for example, herbs and spices) at
optimal concentrations for the elderly (i.e., flavor enhancement)
can improve food enjoyment and have a positive effect on food
intake. Moreover, an association was found between number
of drugs used and preference for dairy products, meaning that
more drugs are taken less dairy products are welcome. To date
the drug effects on food preference has not yet been studied.
Study limitations and strengths
Previous results should be evaluated considering that the
main limitation of this study is the relatively low size of the
sample studied and imprecise measures of some predictors
(e.g. smoking and drugs). Regarding drugs use effect, we
have evaluated only the number of drugs and not the types
of drugs, so we are not been able to consider the different
effects of different types of drugs on olfactory performance.
Another limitation concerns the number of factors considered
in the model that might increase the chance for a type 1 error.
In addition, we found a good prediction for the olfactory
sensitivity, and a moderate prediction for the perception of
sweet and bitter (by measuring with PROP), whereas we did
not find predictors (<10% of explained variance) for salty and
sour tastes. Regarding the four “food preferences” factors,
only for the “spicy food” score we found a moderate prediction
(12%); however, a number of residual correlations remain
unexplained. On the other hand, the main strength of this study
relies in the strict inclusion and exclusion criteria applied. The
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MULTIDIMENSIONAL EVALUATION OF ENDOGENOUS & HEALTH FACTORS
choice of these criteria was carried out in order to avoid the
bias of a very heterogeneous population, a common error on
these studies that contributed to the contradictions reported
in this discussion. Further strengths of this study were (i) the
scaling and validation of food preferences scores, and (ii)
the collection of different predictors of the taste and smell
perception, individually studied in the previous literature,
that were included in the multivariate model that tested their
independent effects. These factors combined with rigorous
inclusion and exclusion criteria used improved the quality of
the results obtained with respect to previous literature.
Conclusion
Our study suggested that age has a negative effect on salty
and sweet taste and smell perception and food preferences.
Drug use had a negative effect on smell perception, while BMI
had a positive effect on sweet perception. Last, variations in
taste receptor genes can result in differential perception of
sweet, acid and bitter tastes.
From a clinical point of view, the results of this study
provide new insights on which and how endogenous and
health (prognostic) factors affect on taste and smell, in order
to be include them into an integrated nutritional assessment
linked to a personalized dietary approach. The tests that we
used to evaluate taste and smell are heterogeneous, because
we wanted to choose the tests easier to perform, less expensive
and requiring less time so they could be easily reproduced and
used in everyday clinical practice. Nutritional rehabilitation
does not end with screening the nutritional status, but rather
begins with that. Individual diet has to follow the determination
of personal nutritional guidelines. In fact, it is necessary to
consider that the dietary approach should always be tailored
taking into consideration various endogenous and health
factors that, in turn, determine alterations of taste and smell and
changes in food choices. Therefore, further studies, conducted
with a larger number of subjects and in both women and
men, might be needed to confirm and improve the findings of
our study. For example, confirmatory statistical models, in a
Structural Equation Models framework (94), might be useful
to evaluate the effects of the selected prognostic factors on the
food preferences and specific body composition outcomes (e.g.
android and gynoid fat), mediated and moderated by taste or
smell performance.
Finally, increased awareness concerning the importance
of personalized nutritional care will contribute to further
improvement in care quality among healthcare professionals
and hospital policy makers.
Statement of funding: There was no funding source for this study. The corresponding
author had full access to all the data in the study and had final responsibility for the
decision to submit for publication.
Competing Interest: Disclosures: Dr. Davide Guido reports no disclosures; Dr.
Simone Perna reports no disclosures; Dr. Maura Carrai reports no disclosures; Prof.
Roberto Barale reports no disclosures; Prof Mario Grassi reports no disclosures; Prof.
Mariangela Rondanelli reports no disclosures.
980
Acknowledgement: We thank Dr. Luca Giacomelli, professional scientific English
editor, for his support in the revision of the paper for the English language.
Ethical Standards: Human and Animal Rights. The study was approved by the
regional ethics committee and was therefore performed in accordance with the ethical
standards laid down in the 1964 Declaration of Helsinki and its later amendments.
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