SACCHARIN CONSUMPTION INCREASES FOOD CONSUMPTION IN RATS

Drinking saccharin increases consumption of simultaneously available food. Hydrational properties of the saccharin solution, learning, and increased

fuel storage all appear to play a role in this increased food intake in rats under these experimental conditions.

The consumption of sweet foods and drinks is common in the American culture and has been held at least partly responsi- ble for many health hazards, including heart disease and dental caries. In particu- lar, consumption of sweet foods and drinks has been seen as contributing to obesity.’ Such an adverse effect of sweet consump- tion could be avoided, however, if either the preference for sweets were decreased or sweets contained no calories.

The former alternative appears unlikely. In nature the sweet taste is usually indica- tive of a concentrated source of calories. During humans’ evolutionary history, when food was scarce, such calorie sources were of high survival value. It is therefore not surprising that there appears to be a large genetic component to the preference for sweet and that it is very difficult to remove this preference.’

However, it has proved possible to pro- duce and market a variety of substances that taste sweet but contain no calories. One of the first and still commonly used ar- tificial sweeteners is saccharin.2 Many peo- ple use it in place of sucrose to sweeten drinks, and it has also been used as a sweetener in a large number of manufac- tured food products.

Nevertheless, the question remains as to whether saccharin consumption actually leads to decreases in total caloric intake. In many situations the body compensates for either decreased intake or increased use of calories. As examples, the following facts are known. 1) If exercise increases, caloric intake increases3 2) If total caloric intake decreases, metabolic rate decreases4 3) If a human subject repeatedly consumes a liquid containing a relatively large number of calories, over time that subject will eat a

smaller meal when food is offered directly after consumption of the l i q ~ i d . ~

Therefore, it cannot simply be assumed that substitution of saccharin for nutritive, sweet substances will result in a weight loss or improved weight maintenance; sac- charin consumption might result in changes in food consumption on either a short- or long-term basis. Tordoff and F r i e d n ~ a n ~ - ~ recently reported an elegant series of experiments that investigated whether saccharin consumption affects short-term food consumption by rats and what mechanism@) might be responsible for such effects. Their major concern in conducting these experiments was to ob- tain information concerning the detection and value of sweet tastes, the physiologic bases of ingestive behavior, and the role of learning in ingestive behavior.

Tordoff and Friedman’s initial experi- ment6 provided rats with either a saccharin solution, a sodium chloride solution, an al- mond extract solution, or a glucose solu- tion during 2-h daily periods when the rats had access to a distinctively flavored food. Food consumption on days when food-so- lution pairs were given to the rats was compared with consumption of a differ- ently flavored food on alternate days when the available liquid was water. In a subse- quent test, the rats were given a choice be- tween the two differently flavored foods. The results showed that, in comparison with food consumption when water was the available liquid, food consumption was 1) increased when the saccharin or sodium chloride solutions were simultaneously available, 2) was not changed when the al- mond extract solution was available, and 3) was decreased when the glucose solution was available. In addition, preference for

NUTRITION REVIEWSIVOL 48, NO 3IMARCH 7 9 9 0 163

the food was increased by previous pairing with saccharin or glucose but was unaf- fected by previous pairing with almond ex- tract or sodium chloride. Therefore, sac- charin increased food intake, and sweetness by itself was insufficient to ex- plain this increase. However, sweetness by itself, when paired with a food, does appear to increase preference for that food.

Tordoff and Friedman's subsequent ex- p e r i m e n t ~ ~ - ~ attempted to determine what was responsible for the increase in food consumption that occurs when it is accom- panied by saccharin consumption. The au- thors first examined the possibility that saccharin increases food consumption due to the hydrational properties of the sac- charin s ~ l u t i o n . ~ In other words, they inves- tigated the hypothesis that saccharin con- sumption exerted its effect because the saccharin solutions used were hyposmotic and that the subjects needed to consume food in order to restore the optimal level of hydration. It has been shown that hydra- tional state and food intake are related. For example, if organisms are deprived of food, they will consume less food.1° Similarly, if organisms are deprived of water, they will consume less water." Animals need to maintain a certain ratio of food to water in their gastrointestinal tracts in order for di- gestion and absorption of nutrients to be normal.'* In their experiments, Tordoff and Friedman' found that the increase in food intake accompanying saccharin consump- tion was contributed to, but not completely accounted for, by the hydrational effects of consumption of hyposmotic saccharin solution. These researchers found that various hyposmotic solutions resulted in increased food intake and that administra- tion of antidiuretic hormone to the rats in- creased the amount of food consumed along with saccharin. However, food con- sumption increased very little when rats were intubated with pure water, a fact indi- cating that hydration by itself is insufficient to explain the increase in food intake that accompanies saccharin consumption.

Tordoff and Friedmans also asked whether learning contributed to the in-

creased food consumption that accompa- nies consumption of saccharin. Once again, learning appears to contribute to, but not entirely account for, the increase in food intake. Rats that repeatedly consumed saccharin together with a distinctively fla- vored food ate more of that food even when it was not accompanied by saccharin. Fur- ther, if the rats were deprived of food and repeatedly given saccharin along with small amounts of distinctively flavored food, they developed an aversion to the food. Thus, the rats learned to associate distinctive tastes with specific metabolic states that would or would not result in in- creased food consumption. However, learning was not a requisite for increased food intake because the increase occurred even when the food did not contain a flavor that had previously been associated with saccharin consumption.

Finally, Tordoff and Friedmang investi- gated whether the increase in food con- sumption that accompanies saccharin con- sumption might be a function of the cephalic-phase reflexes. These reflexes are stimulus-response sequences related to the ingestion and digestion of food; they immediately follow a subject's direct con- tact with f o ~ d . ' ~ . ~ ~ These reflexes include the secretion of insulin in response to food intake and the gag and vomiting reflexes. The cephalic-phase reflexes are involved in the allocation of ingested calories for ei- ther oxidation or storage. Tordoff and Friedmans found that the cephalic-phase insulin reflex was attenuated but not re- moved after hepatic vagotomy (i.e., dener- vation of the liver). However, the rats did not increase their food intake when sac- charin was also consumed, thus indicating that a hepatic mechanism is involved in the usually observed increase in food intake. Tordoff and Friedmang therefore hypothe- sized the following explanation of the in- crease in food intake that accompanies saccharin consumption. They suggested that this increase is due, at least in part, to the cephalic reflexes responding to the taste of sweet. These reflex responses would enhance digestion and increase the

164 NUTRITION REVIEWSIVOL 48, NO 3IMARCH 1990

allocation of metabolic fuels toward stor- age rather than oxidation, and thus de- crease the amount of energy available to the liver for oxidation. The subject in- creases its food consumption to compen- sate for this decrease. Further, consump- tion of food that compensates for this decrease is reinforcing. The signal to con- sume food originates in the liver, so that a denervation of the liver, while not removing the insulin reflex, will decrease the amount of food consumed when saccharin is simul- taneously available.

Taken together, Tordoff and Friedman’s work shows that consumption of saccharin increases consumption of concurrently available food by rats. This increase ap- pears to be partly due to the hydrational properties of the saccharin, partly due to learning, and partly due to the cephalic- phase reflexes which occur in response to the taste of sweet and which result in in- creased fuel storage. Findings consistent with these have been obtained in human^.^ For example, short-term food intake in- creases when human subjects consume nonnutritive sweetener^,'^ and human sub- jects’ food intake decreases when the taste of sweet is blocked using gymnemic acid.16 It is therefore possible that the same mech- anisms which Tordoff and Friedman have identified as operating in rats in response to saccharin consumption may also oper- ate in humans. If so, unless there were ac- companying increased vigilance regarding total caloric intake, humans‘ consumption of saccharin, in substitution for nutritive sweeteners as an attempt to decrease or maintain weight, would be unlikely to suc- ceed. Not only would the body be likely to decrease metabolic rate in order to com- pensate for the decrease in calories, but food consumption might increase as well.

1. Logue AW. The psychology of eating and drink- ing. New York: WH Freeman, 1986

5.

10.

11.

12.

13.

14.

15.

16.

Parham ES, Parham AR. Saccharin use and sugar intake by college students. J Am Diet

Stern JS. Is obesity a disease of inactivity? In: Stunkard AJ, Stellar E, eds. Eating and its dis- orders. New York: Raven Press, 1984:131-9 Keesey RE, Corbett SW. Metabolic defense of the body weight set-point in eating and its disorders. In: Stunkard AJ, Stellar E, eds. New York: Raven Press, 1 984 :87 - 96 Booth DA, Mather P, Fuller J. Starch content of ordinary foods associatively conditions human appetite and satiation, indexed by intake and eat- ing pleasantness of starch-paired flavours. Appe- tite 1982;3:163-84 Tordoff MG, Friedman MI. Drinking saccharin in- creases food intake and preference. I. Compari- son with other drinks. Appetite 1989;12:1-10 Tordoff MG, Friedman MI, Drinking saccharin in- creases food intake and preference. II. Hydra- tional factors. Appetite 1989;12:11-21 Tordoff MG, Friedman MI. Drinking saccharin in- creases food intake and preference. 111. Sensory and associative factors. Appetite 1989;12:23-36 Tordoff MG, Friedman MI. Drinking saccharin in- creases food intake and preference. IV. Cephalic phase and metabolic factors. Appetite 1989;12:

Adolph EF. Water metabolism. Annu Rev Physiol

Kleitman N. The effect of starvation on the daily consumption of water by the dog. Am J Physiol

Lepkovsky S, Lyman R, Fleming D, Nagumo M, Dimick MM. Gastrointestinal regulation of water and its effect on food intake and rate of diges- tion. Am J Physiol 1957;188:327-31 Powley TL. The ventromedial hypothalamic syn- drome, satiety, and a cephalic phase hypothesis. Psycho1 Rev 1977;84:89- 126 Weingarten HP, Powley TL. Ventromedial hypo- thalamic lesions elevate basal and cephalic phase gastric acid output. Am J Physiol

Blundell JE, Hill AJ. Paradoxical effects of an in- tense sweetener (Aspartame) on appetite. Lancet

Brala PM, Hagen RL. Effects of sweetness per- ception and caloric value of a preload on short term intake. Physiol Behav 1983;30:1-9

ASSOC 1980;76:560-3

37-56

1947;9:381-408

1927;81:336-40

1980;239:G221-9

1986;1:1092-3

NUTRlTlON REVIEWSIVOL 48, NO 3IMARCH 1990 165