Artificial Sweetener: Tastes Great, But Unfulfilling

Modern life is a junk food paradise, with a multitude of options for sweet or salty satisfaction available at the corner store. But humans haven’t always lived in such resource-rich environments, and our brains evolved at a time when finding sufficient food was the preeminent struggle in life. That has led some scientists to propose that obesity is a byproduct of our primitive brains struggling to cope with nearly unlimited access to food, with some even proposing that delicious, unhealthy foods can be as addictive to our unsuspecting brains as cocaine or heroin.

“There’s an argument that the reason that we have an obesity epidemic is because we’re hard-wired to consume and store calories to protect against periods of scarcity, but in the modern world, there are no periods of scarcity, so we just get fat,” said Jeff Beeler, research associate (assistant professor) at the University of Chicago Biological Sciences. “Part of that theory people increasingly argue is that dopamine contributes because the tasty, calorie-rich foods we eat are like drugs of abuse: they activate dopamine release and they generate compulsive behaviors.”

But this theory of obesity fails to resolve a key question: is it the delicious taste that is addictive, or the nutritional value of the food? If it’s the taste, products that use artificial sweeteners or fat substitutes should be just as popular as their high-calorie versions — and could be used as effective substitutes to help people lose weight. But real world results demonstrate that most low-calorie or low-fat options remain far less popular. In a study using rodents, a research team led by Beeler, associate professor of neurobiology Xiaoxi Zhuang, and collaborators James McCutcheon and Mitchell Roitman of the University of Illinois at Chicago looked at the brain and behavior to see whether flavor or nutrition is the stronger motivator.

The study, published in the European Journal of Neuroscience, compared normal, caloric sucrose with artificial calorie-free sweeteners, such as sucralose or saccharin, in a series of experiments designed to test which substance rodents preferred, how hard they would work for each option, and how the two sweet tastes affected the release of the neurotransmitter dopamine. Initial experiments confirmed previous studies showing that mice prefer water spiked with either sweetener to plain old flavorless water, and they would also happily press a lever to receive pellets of either option. Sucrose, which combines taste and nutrition, was slightly more popular than its taste-only competitor sucralose in these tests.

“That would leave you with the impression that either taste or nutrition can be reinforcing, and if you put them together, it’s even more so, like an additive effect,” Beeler said. “But even though both artificial taste alone and nutrition can induce preference, we wanted to know if there is a different quality to it. The question was, will both induce compulsive behavior?”

To answer, the researchers needed to look at how appetite for sucrose and sucralose changed over an extended period of time, as the animals learned their respective values. In a progressive ratio lever press experiment (where seven presses are required to receive the first pellet, fourteen presses for the second, twenty-one for the third and so on), mice worked equally hard for sucrose and sucralose at first. But on subsequent days, their enthusiasm for sucrose stayed high, while the appetite for calorie-free sucralose dropped off to lower levels.

The researchers also tested whether nutrition without taste would still be rewarding enough to motivate mice. Because it’s hard to find nutritional food without flavor, the team used a genetic mouse model lacking certain taste receptors and conducted the same experiments. Even for these flavor-challenged mice, sucrose was preferred to water and considered rewarding enough to work for, while sucralose-spiked water was considered no better than water alone — likely because, without the ability to taste sweetness, the two fluids were indistinguishable.

These behavioral choices mirrored changes in the brain, where McCutcheon measured fluctuations in levels of the neurotransmitter dopamine evoked by food pellets containing either sucrose or saccharin. Dopamine levels rise in response to rewarding stimuli, such as sex, drugs, or food, though whether those changes reflect reward, motivation, or another concept in the brain remains a subject of much debate among neurobiologists. Regardless, the dopamine system of rats responded differently to the two substances, with sucrose producing a larger release of the neurotransmitter compared to an artificial sweetener after several days of consuming both.

Together, these results cast doubt on the idea that obesity is the result of an “an addiction to taste” alone, and suggests why few diet foods or drinks become as popular as the high-calorie varieties they’re meant to replace.

“The key thing we would add here is that in order to get compulsive over-eating, you need to have the nutritional value,” Beeler said. “If you think about it, with the exception of Diet Coke (which is caffeinated), why have diet foods not really become popular? Why don’t we have a lot of diet candy bars, diet potato chips and so on. One reason might be because it’s not actually reinforcing. People don’t go back and eat it.”

Which is not to say that taste is a biological non-factor. In those long-ago days of scarce resources, sweet taste was an important cue predicting which foods would contain sugar, and thus nutritional value. When confronted with a red berry that tasted sweet and a red berry that tasted bitter, the choice would be obvious, and could not only direct an individual toward precious calories, but also away from poison. But a taste cue is only as good as its ability to predict this nutritional value, and as the study demonstrates, the importance of taste fades when its link to nutrition is erased.

“Our preference for sweet taste could be innate,” Zhuang said.”It’s very important for survival, because it’s  important to know early on which food is good and which is not good instead of just waiting for digestion and absorption, which will take too long. But if taste is uncoupled from nutrition, eventually this preference will be extinguished.”


Beeler JA, McCutcheon JE, Cao ZF, Murakami M, Alexander E, Roitman MF, Zhuang X. (2012). Taste uncoupled from nutrition fails to sustain the reinforcing properties of food European Journal of Neuroscience DOI: 10.1111/j.1460-9568.2012.08167.x

About Rob Mitchum (525 Articles)
Rob Mitchum is communications manager at the Computation Institute, a joint initiative between The University of Chicago and Argonne National Laboratory.
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