COMMENTARY

Sugar-Free Paradox: Do Artificial Sweeteners Help or Hurt?

David A. Johnson, MD

Disclosures

September 26, 2022

This transcript has been edited for clarity.

Hello. I'm Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.

The use of sugary additives has been an insidious, "sickeningly sweet" component of the Western diet over the past several decades. As an alternative, we often turn to artificial, noncaloric sweeteners. But does the use of these, paradoxically, also represent a negative trend?

What We Know About Traditional Sugar-Based Sweeteners

Caloric beverages are laden with sweeteners, particularly high-fructose corn syrup, a component that is both cheaper and sweeter than cane sugar.

In a previous article, I discussed some of the real concerns we have around the use of high-fructose corn syrup. Animal models looking at colon cancer suggest that there is an association with acceleration of colorectal neoplasia and that fructose actually incorporates itself into the cancer.

In a study from Gut, investigators from the Nurses' Health Study II (1991-2015) showed that the odds of developing early-onset colorectal cancer increased by more than twofold among women who consumed two or more sugary beverages a day. These results have gained a lot of attention, because those levels of sugary beverage consumption are the norm for so many people. Whether that is a cause for concern should be discussed with patients on an individual basis.

The influence of sugary beverages on inflammatory bowel disease (IBD) has also been a significant focus of research. This is because of the concept that sugary beverages may have an inflammatory component. Inflammation also has an association with diverticulitis, the risk for which is increased in those who consume the sugary beverages.

We also now have a recent study analyzing data from the UK Biobank, which includes information on over 500,000 participants. Using a validated dietary assessment tool, investigators found that the intake of more than one unit of sugary beverages a day increases the likelihood of development of IBD (hazard ratio [HR], 1.51; 95% CI, 1.11-2.05) compared with non-consumers, although the trend was not statistically significant.

The comparison between non-consumers and those consuming more than one unit a day revealed a twofold greater risk for Crohn's disease (HR, 2.05; 95% CI, 1.22-3.46) that was significant, and higher but statistically insignificant risk for ulcerative colitis (HR, 1.31; 95% CI, 0.89-1.92).

Collectively, these results highlight the growing concern about the use of caloric sugary beverages and the heightened risk for a variety of conditions, including nonalcoholic fatty liver disease (where there's unquestionably an association), colitis, and colorectal neoplasia.

Artificial Sweeteners' Effects on the Microbiome

Knowing this, should we shift our patients from the caloric sugary beverages to the noncaloric artificial sweeteners? The answer to that question may be no.

Dr Eran Elinav and his group of brilliant investigators at the Weizmann Institute of Science in Israel have previously published data from controlled animal models showing that the use of artificial sweeteners led to a microbial change that actually predisposed to obesity and diabetes.

In their most recent study, which was published in Cell, they now present data from a randomized controlled trial in humans using the four top noncaloric sweeteners: saccharin, sucralose, aspartame, and stevia. Investigators administered two sachets, three times a day, containing these noncaloric sweeteners, glucose, or no supplement to 120 healthy participants, and then monitored changes in their microbiomes.

After 2 weeks of exposure, investigators observed microbiome changes in all of the participants consuming these agents compared with the control population. Saccharin and sucralose in particular led to significant impairment in glycemic indices.

Investigators then transposed the stool from these individuals receiving artificial sweeteners into germ-free mice. The mice actually mirrored the glycemic response of the individual human participants specific to whatever agent they had received.

This tells us that the noncaloric sweeteners may, in and of themselves, cause harmful changes to the microbiome, and that there may be an individualized response based on the microbiome changes in a particular patient.

Now, whether that predisposes them to glycemic alteration remains to be seen in prospective studies. Nonetheless, these data are quite impressive and certainly back up what's already been shown in animal models.

The Current Understanding

Caloric sugary beverages are probably not such a good thing to consume, and I routinely recommend against these as part of my counsel that a Westernized diet should be avoided. The Mediterranean diet really is the way to go.

When it comes to the use of artificial sweeteners, we're still on the learning curve, but this evidence suggests that they may not be the best thing either. Think of the paradox in that. We're using them in patients who are potentially glycemic, predisposed to diabetes, or obese, and who may have a contradictory response by consuming them.

When it comes to my patients and artificial sweeteners, I tell them to avoid them as best they can, and to employ moderation if they absolutely must use them. The best advice is to drink more water. I think that's really a safe option, at least in present time.

When it comes to dietary manipulation and advice, I don't think we do a very good job. We are what we eat — and drink — and certainly I think we should be more proactive in our advice for patients.

Hopefully this has provided you with some better counsel when you talk to your patients going forward.

I'm Dr David Johnson. Thanks for listening.

David A. Johnson, MD, a regular contributor to Medscape, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease.

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