It seems intuitive that because people with type 2 diabetes (T2D) generally need to avoid sugar, clinicians should recommend eating foods and using recipes containing artificial sweeteners such as sucralose instead.
Splenda, which produces sucralose and other non-sugar sweeteners (NSS), is a sponsor of the American Diabetes Association (ADA) Diabetes Food Hub. Earlier this year, the ADA settled a lawsuit regarding its former director of nutrition’s refusal to approve recipes containing sucralose (Splenda), which she believed “flew in the face of the ADA’s mission.”
Experts agree that while artificial sweeteners may help in certain scenarios, they can also be harmful.
“There’s not a lot of evidence that sweeteners like sucralose provide significant benefits, especially over the long term,” Susan Swithers, PhD, professor, Department of Psychological Sciences and associate dean for Faculty Affairs at Purdue University, told Medscape Medical News.
Swithers authored an article several years ago cautioning that consuming nonnutritive sweeteners in beverages not only fails to prevent disease but also is associated with an increase in risks for the same health outcomes associated with sugar-sweetened beverages, including T2D, cardiovascular disease, hypertension, and stroke.
“At this point, we have pretty good evidence that these chemicals that were once touted as being completely inert are, in fact, not inert,” she said. “We know that they’re unlikely to be toxic in the short term, but they are not benign, and they have consequences. Right now, we have little understanding of the outcomes of consumption of these products chronically.”
What the Science Says
In 2023, the World Health Organization (WHO) released a guideline on NSS that recommended against their use for weight control or to reduce the risk for noncommunicable diseases.
The systematic review and meta-analysis upon which the guideline is based found that high intakes of NSS were associated with increases in body mass index and, as Swithers found, risks of developing T2D, cardiovascular events, and any type of stroke, as well as hypertension, bladder cancer, and all-cause mortality.
In a press release announcing the guideline, Francesco Branca, WHO director for Nutrition and Food Safety, said, “NSS are not essential dietary factors and have no nutritional value. People should reduce the sweetness of the diet altogether, starting early in life, to improve their health.”
The “common” NSS named by WHO included sucralose, as well as acesulfame K, aspartame, advantame, cyclamates, neotame, saccharin, stevia, and stevia derivatives.
If NSS consumption can increase T2D risk, what about people who already have T2D?
Some research suggests that NSS may affect people with and without T2D differently, said Swithers. For example, one small study showed that sucralose enhanced glucagon-like peptide 1 release and lowered blood glucose in healthy patients but not in patients with newly diagnosed T2D.
Similarly, Jotham Suez, PhD, an assistant professor in the Department of Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore, told Medscape Medical News that his group “showed for the first time in 2014 that disruption of the microbiome by artificial sweeteners is causally linked to disrupted glycemic control.”
Recently, the team studied the impact of sucralose, aspartame, saccharin, and stevia in healthy adults and “were surprised to discover that all four sweeteners altered gut bacteria and the molecules they secrete,” he said. However, subsequent glucose tolerance tests in healthy humans showed varying results, “suggesting that human microbiome responses to the nonnutritive sweeteners we assessed are highly personalized and may lead to glycemic alterations in some, but not all, consumers depending on their microbes and the sweeteners they consume.”
Nevertheless, a recent review led by researchers in Mexico concluded that sucralose consumption “is associated with various adverse health effects. Despite being considered safe following previous studies, recent research suggests possible links to systemic inflammation, metabolic diseases, disruptions in gut microbiota, liver damage, and toxic effects at the cellular level.”
In addition, they wrote, “It is crucial to highlight the persistence of sucralose in the body, its ability to cross the placenta, and its presence in breast milk, raising concerns about prenatal and neonatal exposure.”
Sabyasachi Sen, MD, a professor of biochemistry and molecular medicine at The George Washington School of Medicine & Health Sciences, Washington, DC, has led and coauthored preclinical and clinical studies demonstrating the potential ill effects of sucralose and other artificial sweeteners. One showed that sucralose and acesulfame potassium–containing diet soda altered microbial taxa in two pilot studies in healthy young adults; another showed a connection between artificial sweeteners and inflammation.
But Sen’s current work is directed at his team’s finding that sucralose promotes the accumulation of reactive oxygen species and adipogenesis in human stem cells, he told Medscape Medical News. “It is essentially an additive that is clearly harmful to cells. Our concern is that stem cells are going to remain in the system for a long period of time. If it is causing inflammation in these cells, then that may lead to adverse outcomes.”
Ruchi Mathur, MD, director of the Diabetes Outpatient Treatment & Education Center at Cedars-Sinai in Los Angeles, is the principal investigator of a recent study suggesting that non-aspartame NSS and aspartame alone may alter the structure and function of the stool and duodenal microbiomes. Levels of circulating inflammatory markers were also altered in participants who consumed artificial sweeteners compared with in control participants who did not.
In addition to these potential adverse effects, “we have to think about the fact that patients with diabetes often have other comorbidities like obesity and are at higher risk for cardiovascular disease and other conditions,” she told Medscape Medical News. “If you’re taking a patient who’s already at risk for those things and you don’t have a detailed discussion with them about pros and cons, you’re doing them a disservice.”
Industry Interests
Addressing the largely negative but varying findings, Swithers said, “One of the difficulties with getting clear answers about the science is that the food and beverage industry has an interest in confusing the picture. If people are selling or using a product, the best thing is for them not have a clear reason to change their behavior. All that needs to happen is for them to be able say, ‘well, it’s not clear, and we don’t really know what’s going on, so I’m just going to keep doing what I’m doing.’ Then the producers and sellers of that product have won.”
“As Upton Sinclair said,” she added, “‘It is difficult to get a man to understand something when his salary depends on his not understanding it.’ When organizations like ADA appear to be promoting a product like sucralose, and they’re not always being clear about disclosing the funding, I think that’s problematic.”
In fact, some recipes in the ADA’s hub that contain Splenda are marked sponsored, such as the four-ingredient peanut butter cookies; others, such as gluten-free brownies, are not — even though the latter contains “1/4 cup plus 1 tbsp” of Splenda Sugar Blend (Splenda produces several nonnutritive sweeteners, not all of which contain sucralose). Splenda is a sponsor of the ADA’s hub.
Consume in Moderation?
Regarding the use of Splenda products, Robert Gabbay, MD, PhD, the ADA’s chief scientific and medical officer, told Medscape Medical News, “Some people with diabetes are accustomed to regularly consuming sugar-sweetened products, which can make management of their diabetes more challenging. As highlighted in the ADA’s Standards of Care, nonnutritive sweeteners (containing few or no calories) may be an acceptable substitute for sweeteners that contain sugar and calories when consumed in moderation. By providing a diabetes-friendly way to prepare foods people are used to eating, we can meet people where they are in offering support to effectively manage their diabetes.”
Of course, “moderation” means different things to different people. “With sucralose in particular, you can bake with it, you can cook with it, and beverages and packaged foods contain it, so it’s easy to end up overconsuming foods that may be fine if they’re occasional treats but aren’t healthy choices to have every single day,” Swithers said. “If you’re having a cookie containing sucralose once a week, it’s not a big deal, but if you’re having a cookie or a brownie every day, that’s something different.”
“I think ‘everything in moderation’ is a very reasonable approach here,” Mathur said. “Anything too much is probably not good, and that includes sweeteners like sucralose and others.”
Suez, whose team is currently exploring the mechanisms through which gut bacteria interact with nonnutritive sweeteners in the pathogenesis of cardiometabolic diseases, was more circumspect.
“We believe that additional, long-term, and non–industry-sponsored studies in humans are needed before we can make a recommendation in favor or against the use of nonnutritive sweeteners,” he said.
“However, our results demonstrating that nonnutritive sweeteners are not inert, when taken together with a growing body of evidence on potential harms of these sweeteners, merit caution until additional studies are completed,” he added. “Our findings do not imply in any way that sugar consumption, shown to be harmful to human health in many studies, is superior to nonnutritive sweeteners. Sugar consumption should be minimized, especially in individuals with obesity or diabetes. Of all the options, unsweetened beverages, specifically water, seem to be the safest and best options.”
Sen, who also “tries to convince patients to have sparkling or cold bottled water,” instead of artificially sweetened soda, agreed. “If a diabetes patient is trying to choose between sugar and sucralose,” he said, “I’m not sure which one is worse.”
Swithers, Mathur, Sen, and Suez declared no competing interests.
Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.
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