Physiology& Behavior, Vol. 47, pp. 1239-1243. ©Pergamon Press plc, 1990. Printed in the U.S.A.
0031-9384/90 $3.00 + .00
Aspartame Ingested Without Tasting Inhibits Hunger and Food Intake1 P E T E R J. R O G E R S , 2 H A R R I E T C. P L E M I N G A N D J O H N E. B L U N D E L L
Biopsychology Group, Psychology Department, University of Leeds, Leeds, LS2 9JT, United Kingdom R e c e i v e d 5 July 1989
ROGERS, P. J., H. C. PLEMING AND J. E. BLUNDELL. Aspartame ingested without tasting inhibits hunger and food intake. PHYSIOL BEHAV 47(6) 1239-1243, 1990.--The effects on motivation to eat and food intake of administering small amounts of aspartame (234 to 470 rag: lower dose equivalent to the amount of aspartame contained in 1-2 cans of some soft drinks) in capsules to human volunteers were examined in two separate experiments (the second was a replication of the first). The results provided clear evidence of a prominent postingestive inhibitory action of aspartame on appetite: consumed in capsules, aspartame reduced subsequent food intake and, to a lesser extent, motivation to eat. The mechanism underlying this effect has yet to be elucidated. A possibility is that the release of cholecystokinin by phenylalanine, a constituent of aspartame, is involved. A further result was that drinking aspartame-sweetened water did not reliably reduce motivational ratings or food intake (in the first experiment aspartame ingested in capsules significantly reduced food intake compared with the same amount ingested as a sweet drink). One interpretation of these together with previous findings is that the response to consuming aspartame is determined by at least two interacting influences: an inhibitory postingestive effect and a stimulatory effect of its sweet taste. In turn, the relative potency of these influences may be modified by certain other features of the aspartame-sweetened food or drink (e.g., its nutrient content). Another implication of these results is that it cannot be assumed that intense sweeteners will all have equivalent effects on appetite. Aspartame
Food intake
Motivation to eat
Eating behaviour
Sweet taste
Phenylalanine
Cholecystokinin
nin (17), which has been proposed as a physiological mediator of satiety (1,11). Under normal circumstances cholecystokinin is released from the small intestine by the arrival of food (fat and protein) and it inhibits gastric emptying (15), although this may not be the (only) mechanism underlying its satiety effect [e.g., (8)]. Intravenous administration of cholecystokinin reduces food intake in humans [e.g., (18)] and in rhesus monkeys (10). In this latter study intragastric infusions of L-phenylalanine were also given and found to inhibit food intake. A further proposal is that phenylalanine might affect appetitie via its role as a precursor of the neurotransmitters dopamine and noradrenaline (5,26). Their involvement in the control of food intake and feeding patterns is well documented (14); however, it is difficult to predict the direction and the extent of the influence of dietary phenylalanine on the functional activity of central catecholaminergic (and serotonergic) systems [e.g., (9,16)]. Despite these findings, clear evidence of a postingestive effect of aspartame on appetite is lacking. Ryan-Harshman et al. (26) administered large doses (up to 10.08 g) of aspartame and phenylalanine in capsules to human volunteers. Food intake was assessed in a test meal eaten either 1 or 1.75 hours later. There were apparently no statistically reliable effects on food intake, although there were significant changes in plasma amino acid concentrations and ratios. It is worth noting, nonetheless, that in the second of the two experiments food intake was 13% lower than
BECAUSE of its theoretical and practical importance there is currently considerable interest in research investigating the influences of intense sweeteners (e.g., aspartame and saccharin) on appetite and body weight [see (23) for review]. Two issues, the effect of sweetness and the effect of caloric dilution, have been examined in some detail and, for example, several studies suggest that sweetness can stimulate appetite (4, 24, 25). However, in addition to their ability to uncouple sweet taste and caloric content, intense sweeteners may have certain postingestive actions (separate from cephalic-phase responses) with significant consequences for appetite control. Although this possibility has not been widely considered, certain physiological effects of saccharin are consistent with the f'mding of increased food intake following the ingestion of this substance (24). Aspartame, which is a dipeptide (L-aspartyl-L-phenylalanine methyl ester) and is chemically unrelated to saccharin, may also affect postingestive mechanisms. Orally ingested aspartame is rapidly hydrolysed in the intestinal lumen to its primary breakdown products aspartic acid, phenylalanine and methanol (19,21). These compounds are absorbed and enter the general circulation and, for example, significant increases in plasma phenylalanine concentrations occur following the consumption of aspartame-sweetened drinks (28). As far as appetite control is concerned the effects of phenylalanine are likely to be the most important. Evidence indicates that L-phenylalanine is a potent releaser of the hormone cholecystoki-
~This research was partly supported by the Agricultural and Food Research Council (Grant No. FG24/502), and a preliminary report of the results was presented at the Xth International Congress on the Physiology of Food and Fluid Intake, held in Paris, July 1989. 2Requests for reprints should be addressed to Peter J. Rogers at his current address: AFRC Institute of Food Research, Reading Laboratory, Shinfield, Reading, Berkshire, RG2 9AT, UK. 1239
1240
ROGERS, PLEMING AND BLUNDELL
control level after phenylalanine and on average 9.5% lower after aspartame [alanine was used as the control treatment (placebo) in these experiments]. This is similar in magnitude to the suppression of test-meal food intake brought about by 50 g of oral glucose (25) or by acute administration of a potent anorectic drug (22). There is one report that phenylalanine (10 g) significantly reduced subjective hunger (27); however, a follow-up study failed to confirm this finding, and moreover, found no effect on food intake (27). A perhaps crucial, methodological problem in these studies arises from the nature of the experimental manipulation. In RyanHarshman et al.'s study the volunteers were required to swallow up to 24 capsules in some conditions. Many subjects would find this unacceptable, and at the very least the demand characteristics associated with such a procedure are likely to be considerable. Consequently, the variability of their responses may be increased, thereby concealing any effects of aspartame or phenylalanine per se. It is worth mentioning that in the nontechnical literature appetite suppression is considered to be one of the most potent effects of phenylalanine administration (7,13). To what extent is this justified? In the first of the present experiments the effects on food intake of a low dose (234 mg) of aspartame ingested without tasting was examined. This amount of aspartame in 200 ml of water was determined in a previous study to be equivalent in sweetness to a 25% sucrose solution (unpublished data), and is an amount of aspartame that may be consumed in 1-2 servings of a commercial, aspartame-sweetened soft drink. Although the results described above indicated that this amount of aspartame taken in capsules would be unlikely to measurably alter appetite, it was considered that such a study was necessary because, if nothing else, it would help to eliminate one of the mechanisms which might be involved in aspartame's effects on appetite. Moreover, a paradoxical effect was apparent in previous experiments. Aspartame-sweetened drinks increased ratings of hunger (4,25), but there was no corresponding increase in food intake. Indeed a sizeable, although statistically nonsignificant, reduction in food intake was observed (25). In fact, in the first of the present experiments aspartame ingested without tasting produced a clear anorectic effect and, since this was an unexpected finding, the experiment was repeated (with the inclusion of an additional dose level). This second experiment confirmed the result and is also reported here. EXPERIMENT 1 METHOD Subjects The subjects were 12 undergraduate volunteers, 6 men and 6 women, aged 18-26 years. All were of normal weight for height (mean and SD Body Mass I n d e x = 2 0 . 8 - 2 . 1 ) and none of them were currently dieting to lose weight or showed excessive concern with their eating or weight [i.e., they scored low or moderatly low on the Herman restraint scale (12), mean and SD score= 1 0 . 6 - 4.0]. Design and Preloads The experiment was carded out according to a within subjects design. As far as possible, individual subjects were tested on the same day on consecutive weeks. The following preloads were administered in a counterbalanced order: a) 200 ml water plus 2 placebo capsules; b) 234 mg aspartame (13 Canderel tablets, G.D. Searle, High Wycombe, England) dissolved in 200 ml water, plus two placebo capsules;
c) 200 ml water plus 2 capsules containing a total of 234 mg aspartame (13 crushed Canderel tablets). Size 00 gelatin capsules were used. Canderel tablets contain, in addition to aspartame (17% by weight), the vehicles lactose and croscarmellose sodium A. Together the two placebo capsules contained 1.2 g of corn flour, making them equivalent in weight and caloric value to the aspartame-containing capsules. The drinks were served at room temperature and the sweet drink [in (b)] was made up not more than 1 hour before it was consumed. Procedure The subjects were not informed of the purpose of the investigation until after its completion. It was presented as "an investigation of the effects of certain nutrients on taste perception and food choice," and they were told that "one of the nutrients of interest was contained in the capsules because in its pure form it is unpleasant to taste, and therefore you should not bite into the capsules." They were assured that "the nutrients are approved for human consumption." On the morning of each experimental session subjects were required to "eat your normal breakfast," but not to eat after 9:30 a.m. They arrived at the laboratory at 11:50 a.m. and consumed their preload between 11:55 and 12 noon. They first took a sip of the drink to taste and then swallowed the capsules with the remaining drink. Then at 10-minute intervals during the next hour they rated the pleasantness of a 20% sucrose solution (15-ml samples tasted but not swallowed). See (3) for details of this procedure. Food intake was measured in a test meal served at 1:00 p.m. Each subject was presented with a tray containing the following preweighed foods: 20 sandwich quarters containing 2 of a variety of fillings, salad items, biscuits and cakes, fresh fruit and fruit yogurt [see (24) for further details]. Water was available to drink with the meal. Subjects' menus were chosen according to their individual preferences stated at the beginning of the experiment, and they received the same foods on each of the 3 occasions. The amount of food offered (>2,000 kcal) was such that subjects would not be expected to eat it all, and they were invited to "eat to satisfaction." They were tested in groups of 6. Energy intakes were computed with reference to standard food composition tables (20) and manufacturers' data. Statistical analysis was carded out using ANOVA and planned a priori two-sample comparisons were made using Student's t-test (2-tail probabilities). On completion of the study a debriefing session was held in which the subjects were fully informed about its true nature. The study was approved by the Leeds University Department of Psychology Ethics Committee. RESULTS ANOVA revealed a significant effect of preload on test meal food intake, F(2,22)= 4.97, p
0031-9384/90 $3.00 + .00
Aspartame Ingested Without Tasting Inhibits Hunger and Food Intake1 P E T E R J. R O G E R S , 2 H A R R I E T C. P L E M I N G A N D J O H N E. B L U N D E L L
Biopsychology Group, Psychology Department, University of Leeds, Leeds, LS2 9JT, United Kingdom R e c e i v e d 5 July 1989
ROGERS, P. J., H. C. PLEMING AND J. E. BLUNDELL. Aspartame ingested without tasting inhibits hunger and food intake. PHYSIOL BEHAV 47(6) 1239-1243, 1990.--The effects on motivation to eat and food intake of administering small amounts of aspartame (234 to 470 rag: lower dose equivalent to the amount of aspartame contained in 1-2 cans of some soft drinks) in capsules to human volunteers were examined in two separate experiments (the second was a replication of the first). The results provided clear evidence of a prominent postingestive inhibitory action of aspartame on appetite: consumed in capsules, aspartame reduced subsequent food intake and, to a lesser extent, motivation to eat. The mechanism underlying this effect has yet to be elucidated. A possibility is that the release of cholecystokinin by phenylalanine, a constituent of aspartame, is involved. A further result was that drinking aspartame-sweetened water did not reliably reduce motivational ratings or food intake (in the first experiment aspartame ingested in capsules significantly reduced food intake compared with the same amount ingested as a sweet drink). One interpretation of these together with previous findings is that the response to consuming aspartame is determined by at least two interacting influences: an inhibitory postingestive effect and a stimulatory effect of its sweet taste. In turn, the relative potency of these influences may be modified by certain other features of the aspartame-sweetened food or drink (e.g., its nutrient content). Another implication of these results is that it cannot be assumed that intense sweeteners will all have equivalent effects on appetite. Aspartame
Food intake
Motivation to eat
Eating behaviour
Sweet taste
Phenylalanine
Cholecystokinin
nin (17), which has been proposed as a physiological mediator of satiety (1,11). Under normal circumstances cholecystokinin is released from the small intestine by the arrival of food (fat and protein) and it inhibits gastric emptying (15), although this may not be the (only) mechanism underlying its satiety effect [e.g., (8)]. Intravenous administration of cholecystokinin reduces food intake in humans [e.g., (18)] and in rhesus monkeys (10). In this latter study intragastric infusions of L-phenylalanine were also given and found to inhibit food intake. A further proposal is that phenylalanine might affect appetitie via its role as a precursor of the neurotransmitters dopamine and noradrenaline (5,26). Their involvement in the control of food intake and feeding patterns is well documented (14); however, it is difficult to predict the direction and the extent of the influence of dietary phenylalanine on the functional activity of central catecholaminergic (and serotonergic) systems [e.g., (9,16)]. Despite these findings, clear evidence of a postingestive effect of aspartame on appetite is lacking. Ryan-Harshman et al. (26) administered large doses (up to 10.08 g) of aspartame and phenylalanine in capsules to human volunteers. Food intake was assessed in a test meal eaten either 1 or 1.75 hours later. There were apparently no statistically reliable effects on food intake, although there were significant changes in plasma amino acid concentrations and ratios. It is worth noting, nonetheless, that in the second of the two experiments food intake was 13% lower than
BECAUSE of its theoretical and practical importance there is currently considerable interest in research investigating the influences of intense sweeteners (e.g., aspartame and saccharin) on appetite and body weight [see (23) for review]. Two issues, the effect of sweetness and the effect of caloric dilution, have been examined in some detail and, for example, several studies suggest that sweetness can stimulate appetite (4, 24, 25). However, in addition to their ability to uncouple sweet taste and caloric content, intense sweeteners may have certain postingestive actions (separate from cephalic-phase responses) with significant consequences for appetite control. Although this possibility has not been widely considered, certain physiological effects of saccharin are consistent with the f'mding of increased food intake following the ingestion of this substance (24). Aspartame, which is a dipeptide (L-aspartyl-L-phenylalanine methyl ester) and is chemically unrelated to saccharin, may also affect postingestive mechanisms. Orally ingested aspartame is rapidly hydrolysed in the intestinal lumen to its primary breakdown products aspartic acid, phenylalanine and methanol (19,21). These compounds are absorbed and enter the general circulation and, for example, significant increases in plasma phenylalanine concentrations occur following the consumption of aspartame-sweetened drinks (28). As far as appetite control is concerned the effects of phenylalanine are likely to be the most important. Evidence indicates that L-phenylalanine is a potent releaser of the hormone cholecystoki-
~This research was partly supported by the Agricultural and Food Research Council (Grant No. FG24/502), and a preliminary report of the results was presented at the Xth International Congress on the Physiology of Food and Fluid Intake, held in Paris, July 1989. 2Requests for reprints should be addressed to Peter J. Rogers at his current address: AFRC Institute of Food Research, Reading Laboratory, Shinfield, Reading, Berkshire, RG2 9AT, UK. 1239
1240
ROGERS, PLEMING AND BLUNDELL
control level after phenylalanine and on average 9.5% lower after aspartame [alanine was used as the control treatment (placebo) in these experiments]. This is similar in magnitude to the suppression of test-meal food intake brought about by 50 g of oral glucose (25) or by acute administration of a potent anorectic drug (22). There is one report that phenylalanine (10 g) significantly reduced subjective hunger (27); however, a follow-up study failed to confirm this finding, and moreover, found no effect on food intake (27). A perhaps crucial, methodological problem in these studies arises from the nature of the experimental manipulation. In RyanHarshman et al.'s study the volunteers were required to swallow up to 24 capsules in some conditions. Many subjects would find this unacceptable, and at the very least the demand characteristics associated with such a procedure are likely to be considerable. Consequently, the variability of their responses may be increased, thereby concealing any effects of aspartame or phenylalanine per se. It is worth mentioning that in the nontechnical literature appetite suppression is considered to be one of the most potent effects of phenylalanine administration (7,13). To what extent is this justified? In the first of the present experiments the effects on food intake of a low dose (234 mg) of aspartame ingested without tasting was examined. This amount of aspartame in 200 ml of water was determined in a previous study to be equivalent in sweetness to a 25% sucrose solution (unpublished data), and is an amount of aspartame that may be consumed in 1-2 servings of a commercial, aspartame-sweetened soft drink. Although the results described above indicated that this amount of aspartame taken in capsules would be unlikely to measurably alter appetite, it was considered that such a study was necessary because, if nothing else, it would help to eliminate one of the mechanisms which might be involved in aspartame's effects on appetite. Moreover, a paradoxical effect was apparent in previous experiments. Aspartame-sweetened drinks increased ratings of hunger (4,25), but there was no corresponding increase in food intake. Indeed a sizeable, although statistically nonsignificant, reduction in food intake was observed (25). In fact, in the first of the present experiments aspartame ingested without tasting produced a clear anorectic effect and, since this was an unexpected finding, the experiment was repeated (with the inclusion of an additional dose level). This second experiment confirmed the result and is also reported here. EXPERIMENT 1 METHOD Subjects The subjects were 12 undergraduate volunteers, 6 men and 6 women, aged 18-26 years. All were of normal weight for height (mean and SD Body Mass I n d e x = 2 0 . 8 - 2 . 1 ) and none of them were currently dieting to lose weight or showed excessive concern with their eating or weight [i.e., they scored low or moderatly low on the Herman restraint scale (12), mean and SD score= 1 0 . 6 - 4.0]. Design and Preloads The experiment was carded out according to a within subjects design. As far as possible, individual subjects were tested on the same day on consecutive weeks. The following preloads were administered in a counterbalanced order: a) 200 ml water plus 2 placebo capsules; b) 234 mg aspartame (13 Canderel tablets, G.D. Searle, High Wycombe, England) dissolved in 200 ml water, plus two placebo capsules;
c) 200 ml water plus 2 capsules containing a total of 234 mg aspartame (13 crushed Canderel tablets). Size 00 gelatin capsules were used. Canderel tablets contain, in addition to aspartame (17% by weight), the vehicles lactose and croscarmellose sodium A. Together the two placebo capsules contained 1.2 g of corn flour, making them equivalent in weight and caloric value to the aspartame-containing capsules. The drinks were served at room temperature and the sweet drink [in (b)] was made up not more than 1 hour before it was consumed. Procedure The subjects were not informed of the purpose of the investigation until after its completion. It was presented as "an investigation of the effects of certain nutrients on taste perception and food choice," and they were told that "one of the nutrients of interest was contained in the capsules because in its pure form it is unpleasant to taste, and therefore you should not bite into the capsules." They were assured that "the nutrients are approved for human consumption." On the morning of each experimental session subjects were required to "eat your normal breakfast," but not to eat after 9:30 a.m. They arrived at the laboratory at 11:50 a.m. and consumed their preload between 11:55 and 12 noon. They first took a sip of the drink to taste and then swallowed the capsules with the remaining drink. Then at 10-minute intervals during the next hour they rated the pleasantness of a 20% sucrose solution (15-ml samples tasted but not swallowed). See (3) for details of this procedure. Food intake was measured in a test meal served at 1:00 p.m. Each subject was presented with a tray containing the following preweighed foods: 20 sandwich quarters containing 2 of a variety of fillings, salad items, biscuits and cakes, fresh fruit and fruit yogurt [see (24) for further details]. Water was available to drink with the meal. Subjects' menus were chosen according to their individual preferences stated at the beginning of the experiment, and they received the same foods on each of the 3 occasions. The amount of food offered (>2,000 kcal) was such that subjects would not be expected to eat it all, and they were invited to "eat to satisfaction." They were tested in groups of 6. Energy intakes were computed with reference to standard food composition tables (20) and manufacturers' data. Statistical analysis was carded out using ANOVA and planned a priori two-sample comparisons were made using Student's t-test (2-tail probabilities). On completion of the study a debriefing session was held in which the subjects were fully informed about its true nature. The study was approved by the Leeds University Department of Psychology Ethics Committee. RESULTS ANOVA revealed a significant effect of preload on test meal food intake, F(2,22)= 4.97, p
