Nearly $16.5 billion in low-calorie sweeteners were purchased in 2016, and that number is expected to increase to $20.6 billion in 2025. These sweeteners taste like sugar, don’t contain calories, and can prevent tooth decay while helping to manage diabetes and body weight.

Despite all this, little is known about the impact of low-calorie sweeteners on taste preferences, insulin secretion, adipogenesis, the gut microbiome, glucose absorption, and the risk of cardiometabolic disease, said Michelle Pang, BSc, a PhD candidate at Maastricht University Medical Center in the Netherlands.

Dr. Pang and Richard Mattes, MPH, PhD, RD, Distinguished Professor of Nutrition Science, Purdue University, spoke during the minisymposium Not So Sweet? Low-Calorie Sweeteners, Obesity and Metabolic Health on Friday, June 3. The symposium was livestreamed and can be viewed on-demand by registered meeting attendees at ADA2022.org. If you haven’t registered for the 82nd Scientific Sessions, register today to access the valuable meeting content.

One reason for the dearth of reliable research data on low-calorie sweeteners is that not all of them are the same, yet they are often studied together, resulting in conflicting findings.

Because low-calorie sweeteners are all structured differently, the body metabolizes them differently. Ace-K, saccharin, and sucralose are partly absorbed into the systemic circulation and the rest is excreted in feces, Dr. Pang said. Aspartame and Stevia follow the normal metabolic pathway and are either used for protein synthesis or excreted in urine.

The sweeteners also bind differently to sweet taste receptors in the oral cavity, in the gastrointestinal tract, and in adipose tissue, she added. Those that bind to receptors in the oral cavity impact signals sent to the areas of the brain involved in reward and satisfaction. And only some sweeteners­—sucralose, acesulfame-K and saccharin—are able to reach the sweet taste receptors in adipose tissue or the gut microbiome.

“When sweeteners bind to the receptors, different cellular activity will be activated and our gustation branch will also be activated differently in comparison to sugar,” Dr. Pang said. “This might generate different signals or weaker signals through brain areas involved in reward and satisfaction. And clinical studies using fMRI scans have also shown that there was no difference between your reward response to water in comparison to aspartame. Similar findings were also found upon sucralose consumption, whereas for glucose there was a reward response found.”

Dr. Pang pointed to small studies that indicate short-chain fatty acid counteracts lipopolysaccharide-induced inflammation, which means that some sweeteners could play a protective role in adiposity and insulin resistance.

She cited SWEET, a five-year study by a consortium of 29 pan-European research, consumer, and industry partners looking at the long-term benefits and potential risks involved in using a variety of sweeteners and sweetness enhancers in the context of public health and safety, obesity, and sustainability.

While consumption of low-calorie sweeteners is growing, consumption of sugar is still too high, said Dr. Mattes. He noted how World Health Organization (WHO) dietary guidelines and Healthy People 2020 recommend the intake of added sugars should be less than 10% of a person’s energy. Meanwhile, about 50% of children ages 1 to 3 years, about 75% of those ages 4 to 18 years, and about 60% of adults exceed that threshold.

Average sugar intake is about 13% of energy, and the modeling that was conducted during the WHO Dietary Guidelines Advisory Committee indicated that the 10% figure should be closer to 5% of energy, Dr. Mattes said.

One way to better understand the benefits of low-calorie sweeteners is to understand why sweet taste receptors exist throughout the body.

“If a sweet receptor is on a sweet taste cell and it’s activated by a low-calorie sweetener or a nutritive sweetener, it will release a neurotransmitter that activates the gustatory system. If that receptor is on an endocrine, it will generate the release of a transmitter like GLP-1 (glucagon-like peptide-1), a hormone often found in insufficient levels in type 2 diabetes patients. If it’s on a beta cell, it will result in the release of insulin,” Dr. Mattes said. “So, that receptor is serving the role of activating these different tissues to do what they’re planning to do, rather than actually serving as a taste receptor.”

He presented data from a clinical trial looking at how different commercially available low-calorie sweeteners affect body weight.

“Much to our surprise, we found that there were distinct differences between them,” he said.

Sucralose led to a steady decline in body weight over the 12-week trial, while saccharin did not. The study didn’t find any differences in hunger, fullness, desire to eat, or any other index of appetite, nor did it find a difference in energy intake.

“We’re at a bit of a loss as to the mechanism there, but we think it might be worth exploring, and it may be the basis of some of the confusion in the literature that doesn’t take the type of sweetener into account,” he said.

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