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Artificial Sweetener Sucralose Linked to Increased Appetite, Study Finds
Mounting evidence has increasingly associated diet sodas and other low-calorie foods with weight gain. This connection is so significant that the World Health Organization issued recommendations in May 2023 advising against the use of sugar substitutes for weight loss.
Dr. Francesco Branca, director of the WHO’s department of nutrition and food safety, stated that “replacing free sugars with non-sugar sweeteners does not support long-term weight management.”
A recent study now offers potential explanations for why excessive consumption of the artificial sweetener sucralose could be potentially counterproductive. Contrary to expectations, sucralose, when consumed in beverages, may trigger an increase in appetite instead of signaling the brain to reduce food intake.
“Sucralose activates the area in the brain responsible for regulating hunger, and this activation is correlated with elevated hunger ratings,” explained Dr. Katie Page, the study’s lead author and an associate professor of medicine and pediatrics. Dr. Page also directs the Diabetes and Obesity Research Institute at the University of Southern California’s Keck School of Medicine in Los Angeles.
According to Page, participants who consumed water with sucralose reported an almost 20% surge in appetite compared to those who drank water with table sugar.
In the United States, sucralose is a primary component in certain Splenda sugar alternatives. Within Europe, sucralose is identified as E955 and is present in sugar substitutes marketed under various brand names including Candys, Canderel Yellow, Cukren, Nevella, Splenda, SucraPlus, Sukrana, and Zerocal.
This research focused specifically on the effects of sucralose and did not examine other common artificial sweeteners like aspartame, acesulfame-K, and sodium saccharin.
Dr. David Katz, a specialist in preventive and lifestyle medicine, commented via email that the study is “very high quality, employing advanced methodologies and thorough analysis.” Dr. Katz, who founded the True Health Initiative, a global coalition of experts focused on evidence-based lifestyle medicine, was not involved in the research.
Katz noted that the authors presented their findings cautiously yet convincingly argue that “non-caloric sweeteners, particularly sucralose, disrupt typical appetite regulation, potentially leading to negative consequences for weight control and health.”
A spokesperson for Heartland Food Products Group, the manufacturer of Splenda, asserted that low-calorie and zero-calorie sweeteners are supported by scientific research and expert recommendations.
“Healthcare professionals, food safety experts, and reputable health organizations recommend low- or zero-calorie sweeteners such as sucralose for diabetes and weight management,” the spokesperson stated in an email. “This recommendation is based on reliable scientific research indicating that the influence of low- or zero-calorie sweeteners on body weight is comparable to that of water. Sweet-tasting products have been shown to reduce cravings for additional sweets while aiding individuals in managing weight, decreasing calorie intake from added sugars, and regulating blood sugar levels.”
Study Reinforces Existing Research
The concept that artificial sweeteners might amplify hunger signals from the brain is not novel. A previous study, coauthored by Page, indicated that women and individuals with obesity were especially susceptible.
“Prior animal studies have suggested similar effects,” Katz stated. However, he added, “this study represents, to my knowledge, the most conclusive human research to date on the direct impacts on the appetite center.”
Glucose is essential for energy in all body cells. The brain, being a significant energy consumer, utilizes up to half of the sugars circulating in the bloodstream. However, the brain is naturally designed to respond to natural sugars like glucose found in whole fruits and certain vegetables.
Page suggests that artificial sweeteners seem to confuse the brain by signaling sweetness without providing the necessary calories. Scientists propose that when the anticipated calories do not materialize, the brain may trigger signals to increase food consumption.
Study Design: Three Beverage Types, Same Participants
The recent study, published in Nature Metabolism, involved 75 participants who consumed three different beverages on separate occasions: plain water, water sweetened with table sugar (sucrose), and water sweetened with sucralose.
During each session, researchers measured participants’ fasting blood glucose levels, followed by a brain scan using Functional Magnetic Resonance Imaging (fMRI). fMRI tracks blood flow to monitor activity in various brain regions.
“Participants underwent a brain scan, then consumed one of the three drinks, and subsequently returned for another scan,” Page explained.
One beverage contained 300 milliliters of water and 75 grams (approximately 2.5 ounces) of sugar (sucrose), comparable to a 16-ounce sugary soda, according to Page.
Another beverage was sweetened with sucralose to match the sweetness level of the sugar drink. Sucralose is approximately 600 times sweeter than sugar, according to the US Food and Drug Administration. Plain water served as the control beverage.
Throughout the brain scanning process, Page’s team conducted additional blood tests at 10, 35, and 120 minutes post-drink consumption and asked participants to rate their hunger levels.
Kyle Burger, a scientist at the Monell Chemical Senses Center in Philadelphia, which investigates human taste and smell, noted that the study’s strength lies in “its use of repeated measures within the same participants and the integration of diverse methods such as brain imaging, blood analysis, and subjective assessments to validate their hypothesis.” Burger was not involved in the study.
Possible Explanations for Increased Hunger
In addition to finding that beverages with sucralose increased hunger sensations by approximately 17%, Page and her team observed enhanced connections to other brain areas responsible for regulating motivation.
“Sucralose seems to influence decision-making processes,” Page stated. “For instance, we detected heightened brain connectivity between the hypothalamus and the anterior cingulate cortex, which governs the assessment of risks and rewards in decision-making.”
Furthermore, blood tests showed that sucralose did not impact hormones used by the brain to signal satiety and the cessation of hunger, Page indicated.
“There is no signal, no signal whatsoever,” she emphasized. “While there is a sweetness signal, there is no hormonal signal indicating fullness. Sucralose does not affect these hormones.”
However, Katz noted that the combined effects of sucralose may not be universally experienced.
“Individuals with insulin resistance, for example, might be particularly susceptible to disruptions in normal appetite control due to sucralose,” he suggested.
Recommendations for Managing Sweetener Consumption
Current recommendations on managing bodily responses to artificial sweeteners are complex, according to Page. For instance, the American Diabetes Association advises individuals with insulin resistance and diabetes to consume no-calorie beverages and foods, but in moderation.
“As an endocrinologist treating patients with diabetes and obesity, I would never advise increasing sugar intake,” Page stated.
“Instead, I advise my patients against relying on non-caloric sweeteners as a sugar substitute and encourage reducing overall dietary sweetener consumption,” she explained.
Katz concurred, advocating for a taste bud “rehabilitation” approach to decrease overall sugar consumption, regardless of its form.
“A genuinely healthful diet naturally minimizes added sugar, thereby eliminating the need to ‘replace’ sugar with sucralose and related compounds,” Katz stated.
Similar to reducing salt intake, it is possible to diminish sweetener consumption by retraining taste preferences to desire less sweetness. Research indicates that taste buds adapt, causing previously favored sugary foods to taste excessively sweet, or in the case of sodium, overly salty.
Katz advised initiating this process by identifying hidden sugar sources in unexpectedly sweetened foods, as he mentioned in a prior CNN interview.
“Requesting complete dessert abstinence might provoke resistance or failure,” Katz commented. “However, significant amounts of added sugar and sweeteners are concealed in non-sweet foods such as salad dressings, pasta sauces, bread, crackers, and even salty snacks.”
By opting for unsweetened products, he suggests, individuals can potentially decrease their daily sugar or sweetener intake “by a third, or even half, before even addressing explicitly sweet foods.”
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