Do Artificial Sweeteners Cause Glucose Intolerance?

Summary and Comment |
October 23, 2014

Do Artificial Sweeteners Cause Glucose Intolerance?

  1. Anthony L. Komaroff, MD

In mice, artificial sweeteners lead to alterations in the microbiome and changes in glucose absorption.

  1. Anthony L. Komaroff, MD

Noncaloric artificial sweeteners, such as saccharine, sucralose, and aspartame, were introduced to control body weight and lower risk for diseases linked to obesity. Yet the epidemic of type 2 diabetes and obesity has coincided with introduction of noncaloric sweeteners. Most of us assume that the epidemic of obesity and type 2 diabetes led to more use of noncaloric sweeteners. However, researchers in Israel report that the opposite might be true: Use of noncaloric sweeteners might have contributed to the epidemic.

Mice that are given noncaloric sweeteners develop glucose intolerance quickly, compared with mice that are given sucrose or glucose. Introduction of dietary noncaloric sweeteners promptly alters the mouse microbiome to favor biochemical pathways that enhance absorption of calorie-rich glucose and short-chain fatty acids. Giving antibiotics to the glucose-intolerant mice eliminated glucose intolerance, and transplanting feces from sweetener–fed animals into germ-free animals produced glucose intolerance in these control animals, whereas feces transplanted from glucose-fed mice into controls didn't produce glucose intolerance.

Seven healthy human volunteers who did not regularly consume noncaloric sweeteners were placed on a diet that contained noncaloric sweeteners. Within 1 week, four participants developed glucose intolerance. Stool from these people, when transplanted to mice, also produced glucose intolerance. Stool from the three humans who did not develop glucose intolerance did not produce glucose intolerance in mice.


This report argues that, although artificial sweeteners lack calories, they can change the gut microbiome in a way that leads to absorption of more calories and that compromises glucose tolerance. That surprising claim surely will be tested.

Editor Disclosures at Time of Publication

  • Disclosures for Anthony L. Komaroff, MD at time of publication Grant / research support Government of Portugal Editorial boards Harvard Medical School: Harvard Health Publications (Editor-in-Chief)


Reader Comments (20)

Sekip Altunkan M.D Physician, Internal Medicine, Ankara, Turkey

Scientific value of the study was too low. I was very strange to publish such a study of the journal Nature. A non-benefit research for clinicians. Looks like a new toy for researchers working in the laboratory.

Peter Cone BSc. Other, Other, Baker Research Inc.,

As a consumer I feel there is little merit to approval of artificial sweeteners by the FDA, or the American Beverage Association. Had either of these bodies done appropriate, (to this topic), clinical research then we would not be discussing it now?
Indeed, a well designed and implemented study which differentiated between the different 'artificial' sweeteners as well as at least one 'natural' low calorie sweetener such as Stevia, would be of significant benefit to the diabetic community.

Laurie Cree, B.Sc, M.Sc., T.C. Rtd.

How is it that a respected journal such as Nature can publish a study with such apparent deficiencies?

Fernando Almeida, MD, PhD Physician, Nephrology, Faculdade de Ciências Médicas e da Saúde, PUC-SP, Sorocaba -Brazil

Very provocative study. Although we have a good body of scientific evidence that sweeteners have no risk for obese and diabetic patients, it is interesting that it could be in contrary. What we know about intestinal microbiome? Let us give a chance to be wrong. The epidemic of type 2 diabetes and obesity deserves it. But no alarm!

Bruce Ammons, Ph.D. Other Healthcare Professional, Private practice, Montana

I remember my fellow grad student working in a taste lab at Duke University in 1980 showing me the differences in cortical taste neuron firing rates when he applied sucrose vs various artificial sweeteners. The latter were so sweet we often heard the neurons ramp up their firing rate until it was a tone and then ... die. I was convinced even then that our neurons didn't know the difference between natural sucrose and artificially produced sweeteners and that the latter, being so overstimulating, had to overdrive our insulin system as well. I figured that they could cause metabolic/diabesity problems even faster. Appears this may indeed be true.

Andy COREN, MD Physician, Family Medicine/General Practice, Office

Interesting. Needs much more research to flush this out. However, one of my patients asked me about this last week. It took only 1 minute of his appointment to acknowledge my ignorance. But 2-3' conversation re web based information, information "overload" and reliable evidence-based recommendations. There went 20% of his appointment. Maybe there should be a disclosure that journalist & websites could be encouraged to use which would help avoid this time waste & sometimes misinformation. Most people automatically give more credibility to research findings than clinicians do.

Pete Other, Other

Andy, given that about 50% of your fellow respondents consider this subject worthy of further investigation, I dont expect it is a time-waste for patients to ask the question. Nor is it a time-waste for you to give them the only advice which is meaningful at this point in time. The studies are very small, may not translate into humans, but nonetheless raise legitimate concerns which coincide with other observations. Diabetes patients can wing it, or if concerned enough restrict their use of artificially-sweetened beverages until further research is undertaken. After all, artificially-sweetened diet soda is not an essential food and if the need is great enough can be replaced by H20.

michael reinstein m.d. Physician, Psychiatry, retired

As a diabetic physician who was addicted to diet soda I have had much better diabetic control by limiting my diet soda

Debra Judelson MD Physician, Cardiology, Cardiovascular Medical Group of Souther California
Competing Interests: Consultant for the Calorie Control Council

As a consultant for the Calorie Control Council, I read this entire study. I was underwhelmed by the authors' conclusion in the human study suggesting adverse results since there was only a 1 person difference in the outcome. This study goes against what we know as clinicians as well as what our patients tell us.

Rob Armbruster Physician, Internal Medicine, Tucson, AZ

Another much better randomized study in humans recently showed favorable results for artificial sweeteners. 200 obese patients were randomized into 2 groups for 1 year. Both groups were given a closely supervised diet and exercise program, but one group could drink all the diet drinks they wanted, and the other group were told not to. Both groups lost weight, but the diet drink group lost even more weight than the other group. So I doubt the artificial sweeteners caused any glucose intolerance.

People, let us pay more attention to the higher quality studies in humans.

maryse gershoni Physician, Pediatric Subspecialty, israel

as far as I remember this article when the controlled study stopped patients who continued with diet soda(S)gained back more weight than patients who got used to drink just water R8

eugene nicholson Kaiser Permanente NW

Would you mind sending me a citation of the study you mentioned? As a pediatrician with a diabetes specialty, this topic interests me. Many thanks! Gene

Antonio Mattos Other Healthcare Professional, Epidemiology/Statistics, Dante Pazzanese Institute of Cardiology

Typical not conclusive results that need more attention when is sharing with population.

Malik Ibrahim Physician, Neurology, TN

Scientifically speaking , this is a pilote study which answered the possibility of simple question. Further larger well designed study is required for more accurate scientific answer. Having said that, I have seen the conclusion rather than pilote study it selfto assess its validity. In another ward there is nothing approved or disapproved

Tor Ole Kjellevand, MD

Very interesting, and in line with my own theories.

American Beverage Association, ABA Communications

This study fails to debunk the vast body of science, including numerous human studies, which establish that low-calorie sweeteners do not adversely impact blood glucose control or uniquely cause obesity. Among its many limitations, this research is largely focused on rodents, and its results are based on small sample sizes. Moreover, leading health organizations such as the Academy of Nutrition and Dietetics (AND), the American Diabetes Association (ADA) and the American Heart Association (AHA) maintain that low-calorie sweeteners are beneficial for weight control and diabetes management. This position is based on the available body of scientific evidence, and the approval of these sweeteners by regulatory agencies around the globe. In sum, these “findings” are inconclusive to say the least, and consumers can continue to enjoy low-calorie sweeteners with confidence.
-American Beverage Association

Leng- Chee Kee Physician, Family Medicine/General Practice

It was not surprising to my relative, a well acknowledged immunologist with both medical and science degrees.

Filip Zemek Other Healthcare Professional, Pharmacology/Pharmacy

Presented findings are very serious and effort to clarify this issue should be made. Many physicians and particularly patients feel that using noncaloric artificial sweeteners is beneficial and are inclined to over use them.

CHARLES DE SOCARRAZ Physician, Internal Medicine

Voila un article utile

Hulki Meltem Sönmez Other, Internal Medicine, A. Menderes Univercity

This is an interesting and serious problem that might be investigated and cleared out.

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