The Skinny on Sweeteners

As someone who became weight-conscious just as Splenda® was coming on the market with the slogan, "it takes like sugar because it is made with sugar," I ate up the promise of no guilt sodas and sweets, literally. And I have been a loyal customer ever since, always carrying a few packets, in various forms of disintegration, in my purse, just in case. So needless to say I approached the recent warnings on the potential harmful side effects of artificial sweeteners with much interest, and I should add, skepticism. Previous studies have shown mixed results and often were conducted with very small sample sizes. That said I found the study published in Nature last week, “Artificial Sweeteners induce glucose intolerance by altering gut microbiota”, intriguing, albeit not without it’s drawbacks (Suez et al., 2014).

First off, the authors look at the effects of three common non-caloric artificial sweeteners (NACs) on glucose tolerance in mice. Glucose tolerance is a test that measures clearance of glucose from the bloodstream, usually two hours after ingesting glucose. Elevated levels are an indicator for insulin resistance and pre-diabetes. Sucralose (in Splenda®), aspartame (in Equal®), and saccharin (in Sweet’N Low) all led to higher glucose levels in mice, although by the final two hour time-point, the difference to the control group became less significant. For the rest of the studies, they focus on saccharin and show that there is still a significant effect on glucose levels when lower doses, corresponding to the FDA’s maximum acceptable daily intake (ADI) dose are given for five weeks.

In recent years, the importance of commensal bacteria living in the gut (the gut microbiota) in immunity and metabolism has become appreciated. Therefore the scientists wanted to determine if gut microflora had an impact on the mice's response to saccharin. Remarkably, saccharin ingestion no longer led to glucose intolerance when broad-spectrum antibiotics were given to mice concurrently with saccharin for four weeks. The author’s measured the composition of the types of bacteria present in the stool of the mice fed both diets and discovered that the composition of the microbiome was distinctly different from the control mice and that it had changed considerably from before the mice were given saccharin.

To determine a causal relationship, the scientists took bacteria-containing stool from saccharin-fed mice and transplanted them to the control mice, which then exhibited glucose intolerance when measured six days later. Stool from control mice cultured in vitro (in culture, outside the body) and then transplanted to non-sweetener-fed mice also had glucose tolerance impairment, providing strong evidence that saccharin changes the type of bacteria present in the gut, which in turn negatively effects the metabolism in mice.

But what about humans? Here they look at 381 non-diabetic people and using questionnaires about food intake, including sweetener use, they find a positive correlation between long-term sweetener use and several parameters of metabolic impairment, including glucose intolerance tests. In the final, and perhaps most startling part of the study, seven individuals with no history of sweetener use were given the FDA ADI dose of saccharin for six days, glucose tolerance was measured, and stool samples were taken for analysis of the gut microflora. Four out of the seven showed impaired glucose tolerance. Interestingly these “responders'” microbiome was very different from the “non-responders'” (those whose glucose levels did not change significantly after being given saccharin) and the microbiome of the responders changed after treatment while the non-responders did not. Finally, stool from responders was able to induce glucose intolerance when transplanted to mice while non-responders’ did not.

These final results are very intriguing but the sample size is so small as to make it hard to make definitive conclusions. In case you are curious as to whether the doses given (360 mg) were comparable to what an average user may ingest, 360 mg of saccharin would be the equivalent of 10 packets of SweetN’ Low® (so maybe 5 cups of coffee with 2 packets each). Most sodas stopped using saccharin awhile ago, but Tab soda, where available, contains 64 mg of saccharin, so 5 to 6-12 oz. cans of Tab everyday are needed to reach the levels in the study. 

Still, the study is important and deserves its publication in the prestigious journal, Nature. It is not the first study to discover a change in microflora with sweeteners. It appears, that Splenda® leads to changes in gut microbiota in mice as well (Mohamed et al., 2008) and led to increased glucose levels in the blood and humans (Pepino et al., 2013), although only seventeen people were tested in the latter study. Of course, it makes me interested to know if I am a responder or not and if we can eventually take stool samples and predict whether a persons’ microbiome will be negatively affected by sweeteners? While I would not advocate for others to change their sweetening habits based on this study, I would strongly suggest for similar studies with larger population sizes and perhaps lower, more normal doses, over longer periods of time. 

References:

Mohamed B., et al. (2008). Splenda Alters Gut Microflora and Increases Intestinal P-Glycoprotein and Cytochrome P-450 in Male Rats. J. Tox & Env Health, 71. doi: 10.1080/15287390802328630.

Pepino M. Y., et al. (2013). Sucraolse affects glycemic and hormonal response to an oral glucose load. Diabetes Care. doi: 10.2337/dc12-2221.

Suez, J., et al. (2014). Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. doi:10.1038/nature13793