Artificial Sweeteners and the Brain

March 31, 2020

Written by: Nitsan Goldstein


Have you ever opened up a Diet Coke only to have someone ask you “Don’t you know those diet drinks cause cancer?” or “Those make you gain more weight than regular soda?” Everyone knows that consuming high amounts of sugar is unhealthy and can cause weight gain. A significant amount of the sugar we consume comes from beverages like soda, juice, and sweetened coffee. To reduce calorie intake, many people instead consume artificially sweetened beverages. However, the health benefits of switching to artificial sweeteners are controversial. Here, we’ll break down some leading theories regarding how artificial sweeteners influence metabolism and the brain. As you’ll see, while significant progress has been made, a clear conclusion regarding the health benefits of artificial sweeteners has yet to be reached.


What are artificial sweeteners?

You may know their names (aspartame, sucralose, and saccharin are a few commonly used sweeteners), but what exactly are artificial sweeteners, and how are they different from caloric sweeteners? Both caloric and non-caloric sweeteners bind to the same types of receptors in the mouth. The brain interprets the binding of these receptors as the pleasant taste we know as sweet. However, unlike artificial sweeteners, caloric sweeteners (sugars such as glucose and sucrose) are metabolized and used as energy by cells in the body.

Sugars are broken down in the intestine, absorbed by the lining of the intestine, and transported to the blood (see Figure 1). Heightened blood glucose levels signal the pancreas to release insulin, which allows glucose to enter the cells. Insulin, along with other hormones, acts in the brain to reduce hunger and make you feel full. These actions combine to decrease food intake, blood glucose, and insulin release until the next meal. This tightly regulated cycle ensures that blood glucose levels remain within normal ranges. When the balance of blood glucose levels, insulin release, and cellular uptake of glucose is impaired, metabolic diseases such as obesity and diabetes may occur. For example, most of us consume far more sugar that our cells need to properly function. This necessitates storing of glucose as glycogen in muscles or lipids in fat tissue, which causes weight gain. Artificial sweeteners, on the other hand, are not sugars and therefore do not contain calories and can’t be used by the body as energy. So how could they possibly lead to weight gain?

Figure 1. Glucose digestion and metabolism. When sugar is consumed, blood glucose levels rise. Insulin is released in response to act in the body and brain to bring blood glucose levels back down.

A leading hypothesis is that while artificial sweeteners themselves do not contain calories, they cause a dysregulation of sugar metabolism, leaving the body less equipped to properly digest and use food. 


Theory 1: Uncoupling taste from calories

How does dysregulation of glucose metabolism result from consuming artificial sweeteners? Several theories have been proposed to explain this relationship using both animal models and human participants1. One theory is that frequent consumption of artificial sweeteners uncouples the brain’s association between sweet taste and calorie-rich food2. When the brain senses sweet taste in the mouth, it is usually followed by the digestion of sugar. Evidence suggests that the brain learns this association, and can send signals that “prepare” the body for increases in blood glucose levels by secreting insulin, for example. This signal from the brain precedes the digestion of the sugar, and ensures that the glucose is properly absorbed and metabolized when it reaches the blood3.

While artificial sweeteners activate the same sweet receptors in the mouth, they are not followed by any glucose digestion or metabolism. The theory is that when artificial sweeteners are consumed frequently, the brain no longer associates sweet taste with calorie-rich foods, and stops signaling the body to prepare to respond to increased blood glucose levels2. Thus, when you consume sugar the response is less efficient and may result in excess blood glucose and weight gain. Recent work has challenged this theory, however, suggesting that it is not the artificial sweetener alone that is the problem. The dysregulation results from consuming artificial sweeteners together with sugar, even in the form of carbohydrates. Since carbohydrates are present in most meals we eat, it is quite common to simultaneously consume both artificial sweeteners and carbohydrates4.


Theory 2: artificial sweeteners disrupt simultaneous carbohydrate metabolism

A new study published just a few weeks ago offers a new perspective on how artificial sweeteners may dysregulate glucose metabolism4. While the findings do not quite fall in line with the uncoupling theory, the basic premise is the same. Artificial sweeteners, though they do not contain calories themselves, affect your body’s ability to most efficiently process other food. In this study, researchers gave participants a drink flavored with caloric sweetener, a drink flavored with an artificial sweetener, or a drink flavored with an artificial sweetener but containing a caloric, tasteless carbohydrate. The participants drank the beverages over the course of two weeks. The researchers then measured how their bodies responded to ingestion of glucose before and after these two weeks.

They found that the level of insulin released in response to glucose was unchanged or slightly lower after the two weeks than it was before the two weeks for participants that drank the caloric or artificially sweetened beverages alone. The uncoupling theory would predict that after two weeks of drinking artificially sweetened beverages, the insulin released in response to glucose would have been different than if the participants drank beverages with caloric sweetener. Instead, subjects that drank the artificially sweetened beverages in combination with carbohydrates showed changes in their insulin responses. The amount of insulin released after glucose was higher after the two weeks than it was before. This suggests that more insulin was needed to bring the blood glucose levels back down to normal. This decrease in insulin sensitivity is a sign that the glucose is not being processed and metabolized efficiently, which may result in weight gain and other adverse health effects.

The researchers also examined how sweet taste affected brain activity in these subjects before and after the two weeks. Sweet taste is known to increase activity in many regions throughout the brain, including centers that monitor the body’s energy state as well as respond to rewards. They found that brain activity in these areas was reduced in participants who showed decreased insulin sensitivity (those that drank the artificial sweetener with carbohydrate beverage).

How does this relate to insulin, and why might adding carbohydrates to an artificially sweetened beverage result in decreased insulin sensitivity? The answers to these questions are not known, though there are several possible explanations. For example, sweet taste receptors are not only expressed in the mouth. They are also expressed in the gut, and there is evidence that binding to these receptors in the gut can affect the proteins that control sugar absorption into the blood5.

It is unclear if the decreased brain activity observed in this study in response to sweet taste is a result of decreased insulin sensitivity, one of the causes of decreased insulin sensitivity, or just associated with the changes in insulin. In any case, decreased activity in these regions may lead to a decrease in feeling full, increasing food intake, and potentially exacerbating weight gain.


The Bottom Line

We are far from understanding the precise ways in which artificial sweeteners interact with the complex systems in place to digest sugars and other foods we consume. As research continues, it is clear that artificial sweeteners likely have some adverse effects on our metabolism that may lead to weight gain and other adverse consequences. How these consequences compare with those of consuming large amounts of sugar is an important individual and societal consideration that will continue to be informed by studies like those discussed here.




  1. Burke, M.V. & Small, D.M. Physiological mechanisms by which non-nutritive sweeteners may impact body weight and metabolism. Physiol. & Behav. 152, 381-388 (2015).
  2. Swithers, S. E., & Davidson, T. L. A role for sweet taste: Calorie predictive relations in energy regulation by rats. Behavioral Neuroscience 122, 161–173 (2008).
  3. Power, M.L. & Schulkin, J. Anticipatory physiological regulation in feeding biology: Cephalic phase responses. Appetite 50, 194-206 (2008).
  4. Dalenberg J.R., et al. Short-Term Consumption of Sucralose with, but Not without, Carbohydrate Impairs Neural and Metabolic Sensitivity to Sugar in Humans. Cell Metab. 31, 493-502.e7 (2020).
  5. Laffitte, A., Neiers, F., & Briand, L. Functional roles of the sweet taste receptor in oral and extraoral tissues. Curr. Opin. Clin. Nutr. Metab. Care 17, 379-385 (2014).



Cover Image from Wikimedia Commons and Evan-Amos (public domain)

Figure 1 created with BioRender

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