J. Anim. Physiol. a. Anim. Nutr. 86 (2002), 90±96 Eingang des Ms.: 06. 03.

2000
Ó 2002 Blackwell Wissenschafts-Verlag, Berlin
ISSN 0931±2439

1
Faculty of Medicine of Lyon Laennec, University of Lyon, Lyon, France, 2Anthropological
Institute and Museum, University of ZuÈrich-Irchel, ZuÈrich, Switzerland, 3Institute of
Animal Nutrition, University of ZuÈrich-Irchel, ZuÈrich, Switzerland

Gustatory responses of pigs to sixty compounds tasting

sweet to humans
By C. NOFRE1, D. GLASER2, J. -M. TINTI1 and M. WANNER3

Summary
The gustatory responses of pigs to 60 compounds perceived as sweet by humans were
studied via a semi-quantitative behavioural method derived from the Richter two-bottle
preference test. Among the 60 compounds tested 35 are effective in pigs, but with an
effectiveness much lower in pigs than in humans. Lugduname and carrelame, which are the
two most potent sweeteners in humans, are also the most effective compounds in pigs.

Introduction
In a previous study (GLASER et al. 2000) we investigated the gustatory responses of pigs (Sus
scrofa) to 33 compounds (14 carbohydrates, 7 polyols and 12 structurally heterogeneous
organic compounds known to taste sweet to humans) by means of a semi-quantitative
behavioural method specially adapted to pigs and derived from the well-known two-bottle
preference test initially proposed by RICHTER (1942). Comparing the relative effectiveness
of these compounds in pigs (from preference tests) and in humans (from their sweetness
potencies) we observed marked differences between the porcine and human responses: e.g.
D-glucose, saccharin and acesulfame-K were, respectively, 2, 3.3 and 8.4 times less effective
in pigs than in humans, while sodium cyclamate and aspartame, which both taste sweet to
humans, were ineffective in pigs. In a recent work (TINTI et al. 2000) we analysed the
gustatory responses of pigs to various a-amino acids and, similarly, we noted signi®cant
differences between the responses of pigs and humans: e.g. D-phenylalanine, D-asparagine,
L-hydroxyproline and D-tryptophan were, respectively, 3, 4, 4 and 15 times less effective in
pigs than in humans, while L-proline, D-leucine and D-histidine, which are sweet to
humans, were ineffective in pigs. In the present work we carry on our comparative tests on
60 synthetic compounds all known to be intense sweeteners to humans.

Materials and methods

Animals
A total number of 120, 63 male and 57 female, pigs (Sus scrofa domesticus) of `Swiss Large
White' breed of between 2 and 7 months old were used for this study. Experiments were
carried out over a period of two years with 10 successive groups (8±12 pigs/group on
average). Each group of pigs was used during a period of approximately three months.
During this period their weight increased on average from 9 kg to 56 kg for the smallest
animals, and from 15 kg to 103 kg for the biggest ones. Animals were fed with a standard
commercial pelleted food (Hokovit-2150 Natura; Hofmann AG, BuÈtzberg, Switzerland;

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 Gustatory responses of pigs 91

containing: crude proteins: 14±15%; crude fats: 2±3%; crude ®bres: 7±8%; calcium: 0.70±
0.75%; phosphorus: 0.45±0.50%; lysine: 7.2 g/kg; methionine and cysteine: 4.9 g/kg;
vitamin A: 4.000 i.u./kg; vitamin D3: 400 i.u./kg; vitamin E: 12 mg/kg; copper: 23 mg/kg;
total energy: 12.5 MJ/kg). During the tests, pigs were housed in individual cages (2 m ´ 3 m)
with concrete ¯oors and straw; each of them was equipped with an automatic, freely
accessible water supply. Experiments were performed only in the morning (between 8 and 9
a.m.), with the animals in a fasting state. As each trial lasted 1 min, each animal was
maintained in the test pen for a period of only ®ve min once a day; during this period no
more than two trials were carried out on each animal. Immediately after the experiments the
pigs were fed with their usual pelleted food.

Chemicals
Sixty organic compounds were tested in pigs: ®ve belonged to the series of 4-cyanoph-
enylureidopropionic acid (cyanosuosan) (Table 1), 11 to the series of 4-cyanophenylcar-
bamoyl-L-aspartyl-3,4-methylenedioxyphenylamine (condate) (Table 2), seven to the
series of N-(S)-2-methylhexanoyl-L-glutamyl-5-amino-2-pyridinecarbonitrile (MAGAP)
(Table 3), 17 to the series of guanidinoacetic acid derivatives (Table 4), 15 to the series of
N-unsubstituted dipeptide derivatives (or analogues) (Table 5) and 5 to the series of
N-substituted dipeptide derivatives (or analogues) (Table 6). With the exception of aspar-
tame (supplied by Sigma AG, Buchs, Switzerland), all the compounds tested were
synthesized according to standard methods described (or cited) in the references listed in
Tables 1±6. Their sweetness potencies in humans relative to a 58.4 mmol/l (20 g/l) sucrose
solution, as given in Tables 1±6, are based on values previously reported (see their
respective references) which were obtained from paired-comparison (two-sample) tests
(AMERINE et al. 1965); in the present work, sweetness potencies are expressed on a molar
basis for reasons of comparability.

Methods
The methodology is similar to that previously described (GLASER et al. 2000). The method
is based on a Richter-type drinking test specially adapted to pigs (see KARE et al. 1965;
KENNEDY and BALDWIN 1972). Two stainless steel containers attached to a wall of the cage

Table 1. Relative effectiveness in humans and pigs of compounds of the series of cyanosuosan,
of general formula: 4-NC-PhNHCONHCH(R)CH2CO2H

Name or Effectiveness Effectiveness

Cpd Ra acronym Ref.b in humansc in pigsd

1 Ph(3,4-OCH2O) CAMPA 1, 2 15 500 0

2 Ph(3,4-diMe) CADPA 4, 9800 0
3 3-Pyridyl 1, 2 9000 0
4 Ph 1, 2 4500 0
5 H Cyanosuosan 3 450 34
a
Abbreviations: Me: methyl; Ph: phenyl
b
(1) MULLER et al. (1991); (2) NOFRE and TINTI (1996a); (3) TINTI et al. (1982); (4) Nofre and Tinti,
unpublished data
c
Sweetness potency on a molar basis relative to sucrose (58.4 mmol/l). For cpds 1±4, their sweetness
potencies are those of their racemic mixtures; in fact, only the S enantiomers appear to be active
(MULLER et al. 1991)
d Preference on a molar basis relative to sucrose (14.6 mmol/l). The ineffective compounds were

tested up to 0.1 g/l for cpd 2, 0.4 g/l for cpds 1, 3, 4

92 C. Nofre et al.

Table 2. Relative effectiveness in humans and pigs of compounds of the series of condate, of
general formula: 4-NC-PhNHCO-L-Asp-NH-R

Effectiveness Effectiveness
Cpd Ra Name Ref.b in humansc in pigsd

1 Ph(3,4-OCH2O) Condate 1 58 000 72

2 Ph(3,4-diMe) Canabate 1 55 000 55
3 Ph(3-CF3) 2 49 000 0
4 Ph(3-OH,4-OMe) 1 46 500 290
5 Ph(3-Cl) 2 34 000 0
6 Ph(3-Me) 2 32 000 0
7 Ph(3-OMe) 2 22 000 0
8 Ph(3-OH) 2 21 500 0
9 Ph(4-Me) 3 16 000 270
10 Ph(3-CH2OH) 2 11 000 0
11 Ph 3 2050 0
a
Abbreviations: Me: methyl; Ph: phenyl.; b(1) NOFRE and TINTI (1997); (2) NOFRE and TINTI
(1998a); (3) Nofre and Tinti, unpublished data. cSweetness potency on a molar basis relative to
sucrose (58.4 mmol/l). dPreference on a molar basis relative to sucrose (14.6 mmol/l). The
ineffective compounds were tested up to 0.08 g/l for cpd 5, 0.16 g/l for cpds 3, 6±8, 10, 0.35 g/l
for cpd 11

Table 3. Relative effectiveness in humans and pigs of compounds of the series of MAGAP, of
general formula: R-CO-L-aa-NH-R¢ where aa is a 2-aminoacyl residue (Asp or Glu)

Effectiveness Effectiveness
Cpd Ra aa R¢a Acronym Ref.b in humansc in pigsd

1 1-Naphthyl Asp Ph-4-CN NAPC 2 22 600 27

2 (S) BuCH(Me) Glu 2-Pyr-5-CN MAGAP 1 21 000 260
3 (R) PhOCH(Me) Asp Ph-4-CN PAAC 1 20 000 0
4 1-Naphthyl Glu Ph-4-CN 3 17 000 0
5 (S) BuCH(Me) Glu Ph-4-CN 1 9400 26
6 Pe Glu Ph-4-CN 2 1000 0
7 Bu Glu Ph-4-CN 2 150 2
a
Abbreviations: aa: 2-aminoacyl; Bu: butyl; Me: methyl; Pe: pentyl; Ph: phenyl; Pyr: pyridyl
b
(1) NOFRE and TINTI (1993b); (2) TINTI and NOFRE (1996); (3) NOFRE and TINTI (1993c)
c
Sweetness potency on a molar basis relative to sucrose (58.4 mmol/l)
d
Preference on a molar basis relative to sucrose (14.6 mmol/l). The ineffective compounds were
tested up to 0.04 g/l for cpd 3, 0.3 g/l for cpd 4, 0.76 g/l for cpd 6

were presented to the animal during a 1-min exposure, in a random left-right position. One
contained the water control (250 ml) and the other an aqueous solution of the test
compound (250 ml). The consumption of the test solution is then determined in relation to
the water control. In fact, before the testing period, each animal was specially trained
during a training period of 3±5 days to differentiate rapidly between a 100 g/l sucrose
solution and the water control; a trained pig is thus able to detect very quickly a palatable
solution (by using a few licks, without drinking, in order to sample the ¯uid palatability)
and to drink the total volume of the palatable solution in less than 1 min, while the volume
of the water control remains practically unchanged.
Thus, after the training period, each animal knows that one of the two containers may
contain a pleasing substance. Less than 20 s are generally suf®cient for a trained pig to
make a choice between the two options and either to drink the preferred ¯uid or to move
away when a palatable solution has not been detected. The standard duration for each test
 Gustatory responses of pigs 93

Table 4. Relative effectiveness in humans and pigs of compounds of the series of guanidinoacetic
acid derivatives, of general formula: R-N = C(NHR¢)NHCH2CO2H

Name,
acronym or Effectiveness Effectiveness
a a
Cpd R R¢ code number Ref.b in humansc in pigsd

1 4-NC-Ph CH2Ph(2,3-OCH2O) Lugduname 1 230 000 10 300

2 3,5-diCl-Ph CH(Ph)2 Carrelame 1 200 000 10 000
3 4-NC-Ph cNn Sucrononate 2 200 000 2500
4 4-NC-Ph CH2Ph(3-Me) Bernardame 1 188 000 2350
5 4-NC-Ph CH(Ph)2 Sucrodiphenate 4 170 000 1100
6 4-NC-Ph cOc Sucrooctate 2 162 000 960
7 3,5-diCl-Ph CH(Me)Ph (S) DMGA 2 128 000 267
8 4-NC-Ph SO2Ph CPGA 5 47 000 520
9 3,5-diMe-Ph CH(Ph)2 3 45 000 141
10 3,5-diMe-Ph CH(Me)Ph (S) 2 28 500 474
11 4-NC-Ph CH(Me)Ph (S) SC 45647 2 26 000 117
12 4-NC-Ph CH(Me)Ph (R) 2 8500 94
13 3,5-diCl-Ph SO2Ph 3 4800 24
14 4-NC-Ph CN CCGA 5 4700 334
15 4-NC-Ph SO2Me CMGA 2 3500 216
16 4-NC-Ph H CGA 5 1700 52
17 3,5-diCl-Ph CH(Me)Ph (R) 3 1000 20
a
Abbreviations: c: cyclo; Me: methyl; Nn: nonyl; Oc: octyl; Ph: phenyl
b
(1) NOFRE and TINTI (1996a); (2) NOFRE et al. (1990); (3) Nofre and Tinti, unpublished data;
(4) NOFRE and TINTI (1993a); (5) NOFRE et al. (1989)
c
Sweetness potency on a molar basis relative to sucrose (58.4 mmol/l)
d
Preference on a molar basis relative to sucrose (14.6 mmol/l)

was thus ®xed at 1 min. Note that the consumption differences between the water control
and the preferred ¯uid are always important: a few ml for the water control against the
total volume (250 ml) for the preferred ¯uid.
A compound is considered as `ineffective' when all the animals tested have no preference
for the compound at any of the concentrations used. A compound is considered as
`effective' at a given concentration when all the animals of a group (8±12 animals on
average) prefer the compound, at the concentration used, over water. The approximate
relative effectiveness of each active compound with regard to sucrose was obtained by
dividing the lowest molar concentration of sucrose able to induce a preference in all the
pigs tested, i.e. 14.6 mmol/l (GLASER et al. 2000), by the lowest molar concentration
(expressed in mmol/l) of the test compound able to elicit a preference in all the pigs tested
at this concentration.

Results and Discussion

The relative effectiveness (on a molar basis relative to sucrose) in pigs and in humans of the
60 tested compounds are listed in Tables 1±6. From these tables the effective minimal
concentration of a compound can easily be obtained in mmol/l by dividing 14.6 by the
reported relative effectiveness. For example, for lugduname (Table 4, Cpd. 1), the lowest
effective concentration observed was 0.001417 mmol/l (14.6/10 300) [i.e. 0.499 mg/l on a
weight basis (mol. wt. 352.3)] and for carrelame (Table 4, Cpd. 2), 0.00146 mmol/l
(14.6/10 000) [i.e. 0.625 mg/l (mol. wt. 428.3)]. For the ineffective compounds the highest
concentrations at which they were tested in pigs are indicated in the tables as footnotes.
The relative effectiveness (preference) in pigs of the active compounds as compared with
their relative effectiveness (sweetness potency) in humans is also mentioned in these tables.
Note that the evaluation methods are based on preference tests in pigs and on comparison
94 C. Nofre et al.

Table 5. Relative effectiveness in humans and pigs of compounds of the series of N-unsubstituted
dipeptides (or analogues), of general formula: L-Asp-R

Name Effectiveness Effectiveness

Cpd Ra or acronym Ref.b in humansc in pigsd

1 D-Abu-NHCH(Ph)Et (S) Atlantame 1 3800 0

2 D-Ala-NH-3-thietanyl- Alitame 2 1950 48
2,2,4,4-tetraMe
3 D-Ala-NHCH(cPr)2 AADA 2 1050 21
4 L-Cys(S-tBu)-OMe ACYM 3 800 11
5 D-Ser-OPr ASPE 4 250 19
6 L-H6Phe-OMe H6APM 6 175 0
7 L-Phe-OMe Aspartame 5 170 0
8 D-Ala-NHCH(Ph)Et (S) AALA 1 130 0
9 L-Tyr-OMe ATM 7 125 1.5
10 D-Ala-OPr AAPE 6 120 4
11 L-Ser(O-tBu)-OMe ASME 3 120 0
12 NHCH(Me)Ph (R) AMBA 8 70 0
13 NHCH(Me)CH2Ph (R) AMPA 9 37 0
14 D-Ala-NHPr AAPA 10 17 0.7
15 NHCH(CO2Me)2 AADD 8 11.5 0
a
Abbreviations: Abu: 2-aminobutyryl; c: cyclo; Bu: butyl; Et: ethyl; H6: hexahydro; Me: methyl;
Ph: phenyl; Pr: propyl; t: tert-
b
(1) D'ANGELO and SWEENY (1994); (2) BRENNAN and HENDRICK (1983); (3) BRUSSEL et al. (1975);
(4) ARIYOSHI et al. (1974); (5) SCHLATTER (1966); (6) MAZUR et al. (1973); (7) MAZUR et al. (1969);
(8) Nofre and Tinti, unpublished data; (9) MAZUR et al. (1970); (10) SUKEHIRO et al. (1977)
c
Sweetness potency on a molar basis relative to sucrose (58.4 mmol/l)
d
Preference on a molar basis relative to sucrose (14.6 mmol/l). The ineffective compounds were
tested up to 0.2 g/l for cpd 1, 1.5 g/l for 6, 5 g/l for 7, 1 g/l for 8, 3 g/l for 11, 1.8 g/l for 12, 3.6 g/l
for 13, 8.8 g/l for 15

Table 6. Relative effectiveness in humans and pigs of compounds of the series of N-substituted
dipeptides (or analogues), of general formula: R-L-Asp-R¢

Effectiveness Effectiveness
Cpd Ra R¢a Name Ref.b in humansc in pigsd

1 Me3CCH2CH2 L-Phe-OMe Neotame 1, 2 11 000 0

2 4-CN-Ph-NH-CO L-Phe-OMe Superaspartame 3 10 000 0
3 Me3CCH2CH2 D-Abu-NHCH Rhodaname 4 9800 122
(Ph)Et (S)
4 (4-OH,3-OMe) L-Phe-OMe Ararame 1 3300 0
Ph(CH2)3
5 Me3CCH2CH2 D-Ala-NHCH 5 2800 28
(cPr)2
a
Abbreviations: Abu: 2-aminobutyryl; c: cyclo; Et: ethyl; Me: methyl; Ph: phenyl; Pr: propyl.
b
(1) NOFRE and TINTI (1996b); (2) NOFRE and TINTI (2000); (3) NOFRE and TINTI (1987);
(4) NOFRE and TINTI (1998b); (5) NOFRE and TINTI (1995)
c
Sweetness potency on a molar basis relative to sucrose (58.4 mmol/l)
d
Preference on a molar basis relative to sucrose (14.6 mmol/l). The ineffective compounds were
tested up to 4 g/l for cpds 1 and 2, 0.5 g/l for cpd 4

tests in humans, two inherently different methods; as a result, the effectiveness ratios
between humans and pigs must be considered only as simple, but useful, estimates.
Among the 60 compounds tested 25 were ineffective in pigs; only 35 displayed an
effectiveness in pigs, ever lower in pigs than in humans (by a factor of 13 to 1000). Note
 Gustatory responses of pigs 95

Fig. 1. (a) N-(4-Cyanophenyl)-N¢-(2,3-methylenedioxybenzyl)guanidinoacetic acid (lugduname) and

(b) N-(3,5-dichlorophenyl)-N¢-diphenylmethylguanidinoacetic acid (carrelame), the two most active
compounds found to date in humans (230 000 and 200 000 times sucrose, respectively) and pigs
(10 300 and 10 000 times sucrose, respectively). In the above formulae both molecules are represented
under their zwitterionic forms.

that lugduname and carrelame (Fig. 1), which, in humans, are the sweetest compounds
found to date (NOFRE and TINTI 1996a), proved also to be the two most effective molecules
in pigs (Table 4).
The value of these studies on the responses of pigs to various types of sweeteners for an
animal scientist is to enable us to understand that taste in pigs operates in a fundamentally
different way to that of man, contrary to generally held belief. Moreover, from these
studies, it appears to be illusory, for an animal nutritionist, to try to stimulate the pig
appetite (when suppressed after weaning, infection or localization to new holdings), and,
for an animal therapist, to try to conceal the bad tastes (e.g. bitterness of certain drugs for
oral use such as antibiotics) with certain usual arti®cial sweeteners (such as aspartame).
From the results of the present work, we suggest that the guanidinoacetic acid derivatives
(such as lugduname or carrelame) could be the most useful compounds for these
applications.

Acknowledgements
The authors are grateful to Prof. Dr Hans Ulrich Bertschinger and Dr med. vet. Esther BuÈrgi for
making animals available, to Roland Liechti and Helena Ciolarro for assistance in carrying out the
experiments, and to Edith Le Bredonchel for technical assistance. The present research is a
contribution to the EU-project, `The Optimisation of Sweet Taste Quality' (TOSTQ) (PL98.4040),
and was ®nancially supported by the `Bundesamt fuÈr Bildung und Wissenschaft' (BBW Nr. 98.0259),
Bern, Switzerland.

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Author's address: C. NOFRE, 114 Cours Albert Thomas, 69008 Lyon, France. E-mail: cnofre@world-
net.fr