Artificial Sweeteners: Still a Matter of Debate

08.15.2018

Questions about benefits and harms remain unanswered

by Judy George
Contributing Writer, MedPage Today

Many people with type 2 diabetes consume artificial sweeteners to control their glucose, but whether this strategy is helpful or harmful is not clear. Moreover, the clinician’s dilemma is how to best advise their patients when pros and cons of using artificial sweeteners seem to change daily.

“The net effect remains a matter of debate because the literature is not decisive, and effects potentially go both ways,” said David Katz, MD, founding director of the Yale-Griffin Prevention Research Center in Connecticut. “It’s not clear that artificial sweeteners actually do reduce sugar and calorie intake over time; they may simply displace them from one source to another.”

No Clear Evidence of Benefit

The FDA has approved six artificial sweeteners: acesulfame-K, aspartame, saccharin, sucralose, neotame, and advantame. About 25% of children and 40% of adults in the U.S. report consuming them on a regular basis, according to Meghan Azad, PhD, of the University of Manitoba.

“This is likely an underestimate because many people consume non-nutritive sweeteners in foods like yogurt and dressings without knowing it,” she added.

“Based on the research done so far, there is no clear evidence for a long-term benefit, but there is evidence of potential harm from the long-term consumption of artificial sweeteners,” Azad said.

In a systematic review of seven clinical trials of artificial sweeteners and cardiometabolic health, Azad and colleagues found that non-nutritive sweeteners had no significant effect on body mass index (BMI). And in 30 observational studies, they found artificial sweeteners were associated with a modest increase in BMI.

Very few studies of artificial sweeteners tracked cardiovascular outcomes like heart disease and stroke, Azad noted, a finding that wouldn’t surprise researcher Per Farup, PhD, of the Norwegian University of Science and Technology. “Most of the favorable effects of non-nutritive sweeteners have been published or sponsored by the producers of the products, and it has been well documented that these publications are heavily biased,” Farup said.

The Azad analysis is by no means the first showing diet sweeteners are not linked to positive outcomes. In 2009, a review of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort demonstrated that consuming diet soda at least once a day was associated with a 36% greater relative risk of incident metabolic syndrome and a 67% greater relative risk of incident type 2 diabetes compared with not consuming diet drinks.

Several reasons could account for these negative associations, observed Susan Swithers, PhD, of Purdue University. One might be cognitive distortions that lead people to overeat. “They think ‘I’m having a diet soda, so it’s okay to have a cookie,’” she said.

But data from pre-clinical models, may offer another explanation.

“Evidence suggests that sweeteners can alter the composition of the gut microbiota, and this can lead directly or indirectly to altered glucose homeostasis,” Swithers noted. “Other data indicate that the sweeteners themselves can trigger release of hormones important in metabolism and glucose regulation, or that experience with consuming the sweeteners can change how the body responds when sugar is consumed.”

Gut Dysbiosis and Beyond

Artificial sweeteners influence the microbial composition of oral mucosa, which may be why dentists view them positively. So in some ways, it’s not surprising they’ve been shown to change gut microbiota in rodents.

“Gut dysbiosis has been mentioned as a causal factor for obesity in humans — it has been proven in animals — and for metabolic syndrome and type 2 diabetes,” said Farup, who currently is studying how artificial sweeteners are associated with disturbed gut microbiota.

In mice, gut microbiota altered by artificial sweeteners has been shown to induce glucose intolerance. And a preliminary study presented at the European Association for the Study of Diabetes (EASD) meeting last year showed that adding sucralose and acesulfame-K to the diets of 27 healthy people was associated with an increase in plasma glucose absorption and altered gut peptides.

While associations do not causation make, clinicians are left with how best to counsel their patients with diabetes and must weigh the risks and benefits of artificial sweetener.

“A ‘sweet tooth’ really is just that — a sweet preference, not a sugar preference,” Katz pointed out. “Artificial sweeteners are intensely sweet and propagate a sweet tooth: they foster and preserve a preference for a sweeter diet overall.”

“The bottom line is that the best data indicate that regular consumption of sweeteners is not linked to improvements in health outcomes,” added Swithers. “Strategies to reduce intake of all sweeteners — whether they have calories or not — are likely to be more beneficial than replacing sugars with sugar substitutes.”