Artificial Sweeteners Like Stevia, Saccharin And Sucralose Causes Glycemic Response Impairment Via Gut Microbiome

A new study led by Dr Kathleen A. Page, a Professor at the Division of Endocrinology, Department of Internal Medicine, Keck School of Medicine of the University of Southern California,-Los Angeles, has found that using artificial sweeteners like stevia, saccharin and sucralose can also cause glycemic response impairment via the gut microbiome and also cause more long term health issues.

The study findings were published in the peer reviewed journal: Cell.
https://www.cell.com/cell/fulltext/S0092-8674(22)00994-1

It is estimated that almost half of adults and 25% of children in the United States depend on NNS for their sweetness cravings. The initial surge in the consumption of these alternative sweeteners was due to their metabolic inertness. However, prospective cohort studies revealed a higher risk of obesity and type 2 diabetes in groups with a higher NNS intake.

However, this correlation has not been unequivocally confirmed by randomized controlled trials (RCTs), which have provided conflicting results. The mechanism of action of these sweeteners on the human gut, as well as their potential to affect human metabolic activity, remains debated.

The current study presents novel insights on how exposure to NNS affects glycemic control in humans through its effects on the gut microbiome. Although previous studies have examined this aspect in rodents, limited studies are available on their impact on humans.

The gut microbiome consists of trillions of microorganisms that are key to human health. When NNS are ingested, they are not digested and, as a result, become available to gut microbes. This subsequently leads to the production of intermediates and byproducts that alter host metabolism.

In the current study, four types of NNS were used to understand how they affected the gut microbiome in 120 healthy adults who had no earlier exposure to these compounds.

This RCT included two arms, one of which involved adults who ingested one of these sweeteners daily for two weeks, with another group ingesting glucose or no sweetener. The dosage was below the acceptable limit.

Study findings
The current study reported specific effects on the microbiome and plasma metabolite profile following ingestion of each type of NNS. In addition, saccharin and sucralose led to poor glycemic responses.

Glucose tolerance was measured using continuous glucose monitoring devices. This allowed the author to understand how glycemic responses varied over the two weeks of the trial in a free-living setting.

Interestingly, the response to sucralose depended on the microbiome profile at baseline.

These findings support the notion that differential human responses to non-nutritive sweetener exposure may be driven by unique host and microbiome features.”

The presence of natural sugars also influenced glycemic responses. Earlier research showed a rapid increase in insulin resistance when sucralose was used with natural carbohydrates.

In the future, potential differences in glycemic responses following NNS intake in individuals with obesity, diabetes, and other metabolic dysregulatory diseases must be measured. The results of this study will heavily impact current advice to substitute NNS for natural sweeteners in such conditions, both for weight loss and to stabilize blood sugar levels.

The changes in gut microbiome composition and function were examined using fecal microbiota transplants from trial subjects who showed the most significant response in germ-free mice with sterile guts. These individuals were classified as responders, indicating that they exhibited poor glycemic responses following NNS ingestion compared to baseline. Conversely, non-responders did not exhibit any change in the glycemic response.

When mice were transplanted with stool samples from responders, they developed impaired glycemic responses. This was unlike those that received fecal samples from non-responders. This indicates that alterations in the gut microbiome underlie the inability to normalize glucose levels when challenged with a glucose load. This condition would otherwise be referred to as glucose intolerance.

Future directions
Shotgun metagenomic sequencing and metabolic pathway analysis were used to examine different species’ structural and functional aspects of the gut microbiome.

Further studies will be needed to correlate these results with insulin and incretin responses alongside glucose levels in response to NNS intake. This will add important information on the hormonal regulation of glucose homeostasis in this situation. In addition, a combination of NNS with natural sweeteners must be used to understand how NNS affects the metabolism of glucose and other natural sugars through the microbiome.

Unraveling mechanisms underlying metabolic consequences of non-nutritive sweetener consumption in humans may enable personalized approaches to nutritional recommendations to improve metabolic health.”