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The surprising literature on artificial sweeteners and their link with obesity and type 2 diabetes

Updated: 8/14/21 8:00 amPublished: 11/10/14

by Emily Regier and Nancy Liu

twitter summary: Artificial sweeteners with zero calories may not be as ‘healthy’ as advertised – new study suggests a link with t2 #diabetes/#obesity

short summary: New research demonstrates a surprising relationship between artificial sweeteners, the microbes that live in your gut, and obesity and type 2 diabetes. How a series of experiments in mice and humans cleverly showed this relationship and what it means for the public...

Read our 2020 article on artificial sweeteners for people with diabetes here.​

The seemingly harmless artificial sweeteners used in diet drinks and “sugar-free” foods (e.g., Sweet N’ Low, Equal, Splenda) may possibly have a connection with high blood glucose levels and an association with obesity and type 2 diabetes. And it may be through a relationship with gut bacteria (“gut microbiome”) – an exciting, emerging field of diabetes and obesity research.

How are artificial sweeteners associated with glucose levels?

In October, the scientific journal Nature published a compelling paper with evidence that eating or drinking non-caloric artificial sweeteners (NAS) like Equal (aspartame), Sweet’N Low (saccharin), and Splenda (sucralose), is associated with glucose intolerance – a condition leading to higher-than-normal blood glucose levels. Glucose intolerance is associated with obesity as well as type 2 diabetes. Strangely enough, these artificial sweeteners – though they have no sugar or calories – may disrupt the body’s ability to regulate blood sugar through changes in the gut microbiome, or the population of bacteria that naturally lives in the digestive system. The study’s results challenge the common assumption of non-caloric sweeteners as a healthy alternative to sugar-sweetened foods and beverages, and present some of the most convincing evidence available on the powerful role of gut bacteria.

What is the evidence?

In a series of carefully controlled experiments, a team of researchers found that adding reasonable doses of artificial sweeteners to drinking water caused significant glucose intolerance in mice. However, these changes were not seen in mice that drank normal sugar-sweetened water, suggesting that developing glucose intolerance may be specifically caused by artificial sweeteners. Next, the researchers cleared the mice’s gut of all bacteria, which reversed the glucose-intolerance effects in the artificial sweetener group. This step demonstrates the crucial role the microbiome has in glucose regulation.

Then, the researchers transplanted feces from the artificial sweetener-fed mice into “germ-free mice” (special mice that have no gut bacteria of their own). The germ-free animals proceeded to develop glucose intolerance from the bacteria transplant, and their new gut microbiome was distinctly different from mice that were fed real sugar instead of artificial sweeteners. Notably, the bacteria involved with carbohydrate digestion and energy storage increased, while bacteria involved with moving glucose decreased, suggesting the animal became more efficient at digestion and storage (which may be related to weight gain).

But what about research in humans?

Many animal studies translate poorly to humans, but a clinical trial of almost 400 people found a signification association between higher artificial sweetener consumption and markers of metabolic dysfunction like higher body weight, A1c, and glucose intolerance. Furthermore, those who consumed higher amounts of artificial sweeteners had a similar microbiome composition as did the mice that consumed artificial sweeteners, showing a consistent pattern between the research in humans and mice.

Finally, in a small trial, the researchers fed artificial sweeteners to people who did not normally consume artificial sweeteners, only to show that those individuals also developed glucose intolerance and a change in their microbiome that mirrored what happened in mice who consumed artificial sweeteners. The researchers conducted several other experiments to eliminate the potential for confounding factors (things that would provide alternative explanations for their results), which made these results particularly compelling.

What does this mean for eating and drinking “sugar free” foods with artificial sweeteners?

These findings are surprising and run counter to popular advice that sugar-free options are a good alternative for people with type 2 diabetes. These experiments were well conducted, but further work is required to confirm that food and drinks with artificial sweeteners contribute to obesity-related conditions by changing bacteria in the gut. But at this stage, this type of research is definitely cause for concern, especially given the high profile journal (Nature) where it was published.          

So what foods should I choose?

  • Overall, diaTribe believes that the best rules of thumb when it comes to choosing foods and drinks are:

  • Choose options with as few ingredients as possible. Be wary of foods with lots of chemical-sounding ingredients that are hard to pronounce.

  • Avoid fast food and highly processed food, and cook at home as much as possible.

  • Eat more fruits and vegetables, aiming for at least five servings per day – see the CDC calculator for more specifics based on your individual needs.

  • Eat in moderation!


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What do you think?