How Artificial Sweeteners Wreak Havoc on Your Gut | Chris Kresser

How Artificial Sweeteners Wreak Havoc on Your Gut

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From soft drinks to yogurt, artificial sweeteners have become commonplace in the food and beverage industry and are recognized as safe by the FDA. Yet a 2014 study found that artificial sweeteners are able to alter your gut microbes, and your health as a result. Read on to learn exactly what the researchers found and how artificial sweeteners might be contributing to the modern epidemic of metabolic disease.

Artificial sweetners are considered safe by the mainstream, when in fact they negatively effect the gut. istock.com/celsopupo

A little over two years ago, I wrote a post titled “The Unbiased Truth about Artificial Sweeteners.” At the time of writing, the scientific literature did not really suggest any significant negative effects of artificial sweeteners. A few studies had found negative effects, but many others showed no correlation at all. While I urged caution in the consumption of these sugar substitutes, there was really no solid evidence at the time to recommend their strict avoidance.

Fast forward to today, and enter the gut microbiota. The trillions of bacteria that inhabit your gastrointestinal tract have received a tremendous amount of attention in recent years. A comprehensive research study has now shown (almost unequivocally) that artificial sweeteners can in fact impact health via altering gut microbes. (1).

Non-Caloric Artificial Sweeteners

A sugar substitute is any food additive that provides a sugary taste but has significantly less associated calories, or food energy. Some sugar substitutes are natural, like stevia, while others are synthetic, termed “artificial sweeteners.”

In the United States, six artificial sweeteners have been approved for use: aspartame, sucralose, neotame, acesulfame potassium (Ace-K), saccharin, and advantame. All have been deemed Generally Recognized as Safe (GRAS) by the FDA (2).

As high-fructose corn syrup continues to receive opposition from consumers and health organizations alike, the food and beverage industry is increasingly turning to artificial sweeteners instead. According to BCC Research, the global market for high-intensity sweeteners is expected to reach almost $1.9 billion in 2017, with the non-nutritive category growing particularly rapidly (3). The most commonly used non-caloric artificial sweeteners (NASs) are saccharin (Sweet’n Low), aspartame (Equal, NutraSweet and Canderel), and sucralose (Splenda).

Did you know artificial sweeteners can cause glucose intolerance?

Most NASs pass through the human GI tract without being digested by the human host. They therefore come in direct contact with microbes in the colon. As we’ll see from the results of this study, this has dramatic implications for the health of the host.

Prolonged Consumption of Non-Caloric Artificial Sweeteners Makes Mice Glucose Intolerant

In the first part of the study, described in Nature, researchers from the Weizmann Institute of Science in Israel added saccharin, sucralose, or aspartame to the drinking water of three different groups of lean 10-week-old mice. They also had several control groups, including mice drinking only water or mice drinking water supplemented with glucose or sucrose, to see how the artificial sweeteners compared to normal sugars.

The researchers then performed a glucose tolerance test. As this is a crucial aspect of the study, I’m going to briefly describe how this is done. All of the mice are given only water for six hours prior to the test so that they are in a fasted state (and the NAS, glucose, and sucrose mice do not continue to eat sweeteners). They are then given 40 mg of glucose orally. Blood from the tail vein is used to measure glucose immediately before and at 15, 30, 60, 90, and 120 minutes after the glucose is given. From these data, the researchers can create a glucose tolerance curve to determine (a) fasting glucose levels, (b) how high the blood glucose spikes, and (c) how quickly glucose is cleared from the bloodstream.

So what did they find?

At week 11 of feeding, the three control groups (water, water+glucose, water+sucrose) had comparable glucose tolerance curves, whereas all three NAS groups (water+saccharin, water+sucralose, water+aspartame) had developed significant glucose intolerance.

Saccharin had the largest effect. They duplicated the experiment, this time in mice with diet-induced obesity, and observed the same result: NAS made the obese mice more glucose intolerant.

Treating Mice with Antibiotics Abolished Glucose Intolerance

The researchers next wanted to see if the microbiota was responsible for the glucose intolerance. One of the simplest methods for determining if the microbiota plays a role in a particular trait or condition is to administer antibiotics and observe any changes. They did exactly this: the researchers treated mice with a combination of ciprofloxacin and metronidazole or vancomycin alone for four weeks and found that antibiotic treatment abolished glucose intolerance in both the lean and obese models.

This suggests that NAS induction of glucose intolerance is very likely mediated by the gut microbiota. However, there is always the slight possibility that off-target effects of the antibiotics on the host abolished the glucose intolerance, rather than the changes in microbiota composition. To rule this out and confirm the causality of the relationship, the researchers turned to germ-free mice.

Transferring NAS Microbiota to Germ-Free Mice Transfers the Glucose-Intolerant Phenotype

I’ve written about germ-free (GF) mice before in several of my blog articles on the microbiota (4, 5, 6, 7). Raised in sterile conditions, GF mice lack any microbes at all but can be selectively recolonized for experiments. Researchers can therefore perform an intervention in normal mice, take their fecal material, and transplant it into GF mice to determine if a particular effect of the intervention is mediated by the microbiota. If it is, the simple act of transferring the fecal material will elicit the effect in the recipient mice.

In this case, the researchers had two groups of mice that would serve as their fecal donors for the experiment, both of which were kept in normal (non-sterile) housing. One group was fed normal mouse chow + saccharin, and the other was fed normal mouse chow + glucose as a control. The amount of saccharin given was the mouse equivalent of the acceptable daily intake (ADI) of saccharin in humans (5 mg/kg, suggested by the FDA).

Fecal pellets from these two groups of mice were then transplanted into two groups of naïve GF mice. The GF recipient mice were therefore colonized by microbes from saccharin-fed or glucose-fed donors but were maintained on normal chow themselves. Six days after the transfer, the researchers performed a glucose tolerance test on the recipients. They found that those mice that received the saccharin-fed microbiota had developed significant glucose intolerance compared to those that received the glucose-fed (control) microbiota. This confirmed the findings in the antibiotic model, suggesting that alterations in the microbiota were in fact responsible for the differential glucose tolerance.

NAS Alters Microbiota Composition and Function

The most pressing research question then was, how had the microbiota been altered? Using 16S sequencing technology, they characterized the microbiota of each group. They found that mice consuming saccharin had a distinct microbiota composition from all three control groups. The authors reported over 40 operational taxonomic units (groups of bacteria) that were significantly altered in abundance, an indication of considerable dysbiosis.

Which bacteria changed? In the saccharin group, the Bacteroides genus increased, while Lactobacillus reuteri and Akkermansia muciniphila (two microbes generally considered to be beneficial) decreased. Several members of the Clostridiales order increased, while other Clostridiales decreased.

They next wanted to look at microbial function, and this is where the technology gets really cool.  The researchers performed shotgun metagenomic sequencing, which allows for mass sequencing the genome of virtually every microbe in the gut. They did this sequencing on fecal samples collected before and after the 11 weeks for all of the groups of mice. The results showed that saccharin-fed mice had a strong increase in genes associated with glycan degradation pathways, which have been linked to enhanced energy harvest and metabolic disease (8, 9).

As if their prior findings in mice weren’t robust already, the researchers also cultured naïve mouse fecal material with NAS. They then transferred the NAS-exposed fecal material, or control fecal material, into GF mice. Recipients of the NAS-exposed fecal material showed increased glucose intolerance compared to GF mice given the control culture and similar alterations in microbial composition to the previous experiment.

What about Humans? NAS Consumption in Humans Is Associated with Impaired Glucose Intolerance

I discussed many of the human studies looking at NAS consumption in my previous article. When that was published, most human studies had shown mixed results with NAS. After finding such robust effects on the microbiota and glucose intolerance in mice, Suez and colleagues decided to see if the findings would translate to humans in their hands. They first performed a cross-sectional study, using a food frequency questionnaire to determine approximate NAS consumption, and also looked at several measures of metabolic disease.

Contrary to previous studies, they found significant positive correlation between NAS consumption and a number of clinical parameters related to metabolic syndrome: weight, waist-to-hip ratio, fasting blood glucose, hemoglobin A1c, glucose tolerance test, and ALT.

You might be thinking: well, sure, it’s correlated because people with excess weight and metabolic syndrome are the most likely to use NAS in place of sugar as a means of losing weight. Luckily, the researchers took this into account and the effect still remained after correcting for BMI.

More Human Evidence

Correlations are great and all, but that’s all they are: correlations. We can’t infer causation from simple associations between consumption of a substance and outcomes. Fortunately, Suez et al. took it to the next level and performed a longitudinal study. Seven healthy volunteers who do not normally consume NAS or NAS-containing foods were followed for one week. On days two through seven, participants consumed the FDA’s maximal acceptable daily intake of saccharin (5 mg/kg body weight) as three divided daily doses. They were monitored by continuous glucose measurements and daily glucose tolerance tests.

Astoundingly, in just this short week-long period, four out of seven individuals had already developed significantly poorer glycemic responses (NAS responders) and pronounced changes in microbiota composition. The remaining three individuals had no change (NAS non-responders). Transfer of NAS-responders’ day seven stool into GF mice resulted in glucose intolerance (compared to day 1 stool transfer), while transfer of NAS-non-responder day 7 stool did not.

Takeaways from This Study

Phew. Hopefully you stayed with me through all that! This was an extremely robust study with lots of different components, but it provides an incredible wealth of evidence against the use of NAS. If you glazed over some of the details, here are the main takeaways:

  1. NAS consumption in both mice and humans increases the risk of developing glucose intolerance and metabolic disease.
  2. The adverse metabolic effects are mediated by alterations in the composition and function of the microbiota.
  3. This study calls for a serious need to reassess the ubiquitous and ever-increasing use of NAS in the food and beverage industry.
  1. Looking forward to an answer to the questions re erythritol & Xylitol – I am also interested in finding out about these sweeteners.

    • I don’t know think I can reference the studies I have correctly here and now where I am. But from what I have read Xylitol and Erythritol feed gut bacteria due to the fact they are seldom properly absorbed or processed and can lead to an “osmotic” situation where they pull water into the bowel.

      Some people that have approached me with a request for a resolve of gut issues and/or flatulence problems, I have found were consuming these sugar alternatives, particularly xylitol, often mixed with vegetable gums added to the processed foods they were consuming.

      Removal of these sugars and gums alleviated symptoms of gastro-intestinal inconvenience.

      This study, https://www.ncbi.nlm.nih.gov/pubmed/17995737

      Although not one of those studies that I have read earlier, this one suggested a level of degradation by bacteria in butyrate of xylitol.

      Does one prefer flatulence and butyrate over a more stable gut?

      There are possibly better ways to induce butyrate into the body.

      • Ooo …. I thought to return to check.

        So many grammar mistakes and missing pieces of logic that I was thinking of at the time. May it be the last time I type something while doing something else at the same time.

        The whole mention of vegetable gums could have been avoided, I added it it in because certain gums also act as prebiotics.

      • Ninety percent of Erythritol is absorbed from the gut and excreted in the urine, it is the least likely of any sugar alcohol to produce flatulence.

        Butyrate is essential for colon health. The colon uses the short chain fatty acids butyrate, propionate, isobutyrate and acetate as its major energy sources. These fatty acids come from bacterial fermentation of fibre and other unabsorbed dietary components. This is why fibre is good for you. Any prebiotic that produces butyrate in your large intestine is great. The colon produces ketone bodies from butyrate, again good for both your gut and you. Butyrate is also found in butter. What the article is saying is that Xylitol is good for colon health! Small amounts of Xylitol are unlikely to produce flatulence. As Xylitol has the same sweetness as sucrose, it is usually available in pure form.

        However, other sugar alcohols like sorbitol and maltitol will produce amazing amounts of gas and make you feel ill, a good way to experience the symptoms of IBS. “Vegetable gums” could quite easily be the culprit too.

  2. Recently my nurse practictitioner informed me of the link found between NAS use and glucose intolerance. After reading your article I realize it may be a factor in my digestive issues and problems with weight control. I have severe SIBO with constipation and have regularly consumed diet sodas over the years. Thanks so much for sharing this. It gives me the motivation to strive for giving them up.

  3. With respect tolow-calorie sweeteners, the body of science debunks the claim that these ingredients uniquely cause weight gain. For instance, a randomized clinical trial published in the American Journal of Clinical Nutrition concluded that those who consumed diet beverages in place of caloric ones consumed fewer calories than other control groups, including those who consumed only water: http://bit.ly/Ik4zjC. Moreover, the rodent study referenced here that alleges diet soda adversely impacts gut microbes fails to prove its bold claims, as discussed in some detail here: http://bit.ly/1tSQDo5. As the Academy of Nutrition and Dietetics has said: “consumers can safely enjoy a range of nutritive and nonnutritive sweeteners when consumed within an eating plan that is guided by current federal nutrition recommendations, such as the Dietary Guidelines for Americans and the Dietary Reference Intakes, as well as individual health goals and personal preference.”

    • Sounds like typical commercial BS, to me. I think it’s interesting that so many “industry spokespersons” seem to think that their industry is just as capable as God, when it comes to ‘creating’ some ‘new’ artificial “food” substances. That ignores the fact “God loves us”, while these commercial interests apparently only ‘love’ our money. As long as profit is the main goal, I predict that businesses will continue to sell ‘poison’ as “safe and effective” alternatives.

      • ABSOLUTELY Jay!
        And I wonder, how such a “comment” could even appear on Chris Kresser’s blog? Is he being watched by a “representative” of the establishment?

  4. Thank you for your article. I consumed 4-6 packets of sweet and low for 15-20 years. I have been on a no-low sugar diet for over a year. I do not eat pasta, bread or minimal rice/grains. No dairy, corn or peanuts.
    I take a probiotic.
    I still have bloating, gas, and stomach pains at least once a week. I haven’t been able to pinpoint the issue, but after reading your article-maybe it is past damage.
    Is my gut flora damaged forever? Is there anything one can do to reverse the affects and how long do you wait to know if it is working?
    What would you suggest for healing gut flora or leaky gut?
    Thank you.

    • I am also wondering if it’s reversible. I am in a similar boat, as you, in which I have overdone it on artificial sweeteners. It’s hard to find anything which explains whether the distortion of the microbiome is reversible.

  5. The first study is on mice. So it can be thrown away.
    The second study is correlational. So it can be thrown away.
    The third study is on 7 people. So…
    It lasted one week. So…
    There was no effect on almost half the volunteers. As there were only 7 people (!), we’re talking about 3 non-responders here. (These numbers are ridiculously low to try to find a population-generalisable effect).
    They took in 5mg per kilo of bodyweight. So, anywhere between 250g-1000g of saccharin, per day, every day. And these were people who don’t usually consume any NAS.

    So what we learn from that study is that: if you don’t consume NAS, suddenly consuming VAST amounts of saccharin every day, might (4-in-7 chance) produce changes (not-specificed good or bad changes) in microbiota composition and significantly (is that statistical significance, or real life human effects significance?) poorer glycemic response, in the very short-term.

    It says nothing about what might happen on day 8; or, what might happen if you only consume normal amounts, not massive amounts; or if your microbiota is already adjusted to NAS; or if your microbiota might adjust to them, perhaps on day 8; or what differentiates the 3 non-responders. There’s not much you can take anyway from a study of just 7 days on just 7 people.

    This is really weak evidence.

    • Your numbers are way off. 5 mg for every kilo is nowhere near that much. I’m 208 lbs, or roughly 94 kilos. So for me, 5 x 94 = 470 milligrams, less than half a gram. That’s really not that much and people who consume NAS regularly could easily exceed that.

      But I agree with you in that mice studies and a human study of 7 participants isn’t nearly enough research to make conclusions yet.

        • I am thinking to make a batch of Sauerkraut and put a bit of NAS in there, better repeat their experiment and instead swap the mice for Sauerkraut.

  6. Thanks, Chris, for a very comprehensive article. I’d seen a brief synopsis of this finding in the popular press, so I appreciate your providing all the technical details of the procedures (yes, I’m a science nerd). I haven’t used fake sweeteners in 15 years because of other concerns I’d had about them. The more fake sweeteners, fake fats and fake-whatever-foods are studied, the more prudent a whole foods/real foods/species-appropriate diet is shown to be.

    • As always happens, the safest template (real food) is the only one that really works.
      Nature is about billions of variables working at the same time.
      It’s really naive and arrogant thinking that we can do better and improve nature.
      Whenever we introduce a new chemical approach that has little to do with what nature meant through eons of evolution, we get burned!
      And sistematically, we don’t learn the lesson.

    • I think that the evolutionary template is the most powerful tool because the approach “innocent until opposite proof” is not good when we talk about novel foods. While it’s true that at first research may not support that X is bad, it’s also true all the other way around.
      I would rather choose the cautionary approach “guilty until opposite proof”, and the evolutionary tool is very good at predicting what may reveal bad for our health.
      Given the interest of food companies to push new stuff for their interest, we need a very cautios approach.

  7. What about xylitol and erythritol? Xylitol effects mouth bacteria and it has limited absorption so probably effects bowel. I understand erythritol is absorbed higher in the digestion and passed via urine, so is it less likely to cause the problem?

    • I struggled through the article , and there is no mention of XYLITOL. As a contributor observed it’s good for the teeth. but is it unbalancing our microbiome when we take it.

      • I don’t think we can definitively say that, unless you know of some studies that have looked into sugar alcohols and their effects on the microbiome.

  8. I have both Fructose Malabsorption and Lactose Intolerance – Verfied with Hyrdogen Breath Tests. I had been a long-term Diet Coke (Caffeine Free) drinker which I stopped around 2007ish. I am very interested in hearing more about this – I hope there is a way to reverse my gut symptoms. I also have been diagnosed with Hashimoto’s Thyroiditis which I think is all connected.

  9. Very interesting. One’s gut feeling about these ghastly sweeteners confirmed.

    Interesting too that one of the main deficits caused was in L. reuteri – low levels of which may be linked to autism symptoms.

    One wonders if autistic symptoms (along with many other things) are worsened by these sweeteners.

  10. You must be very lean. Was your data higher before you used stevia? Are you low carb or keto? Did you start working out?
    I am trying to lean down by fasting and I find fake sugar makes me have cravings and I immediately have weight loss stalls and gains. I can’t touch fake sugars or real sugars without ruining everything. The only sweet I can do is a tiny, tiny bit of fruit.

    • jujjee – what you describe sounds like an “insuline issue” and that you might need more HEALTHY fats in your diet, especially if you want to lose weight.
      Check out Dr. Mark Hyman’s books/blog on this…also his FAT Summit 2 (free on the internet until 14 Nov) where he and experts discuss many aspects related to the topic. He interviewed Chris Kresser as well!

  11. Please explain if the harmful effects and alterations in gut flora from using NAS in the past can be reversed by healthier eating(more natural sweeteners, kefir, fermented foods, etc) or if antibiotics are necessary (followed by reinoculation, I suppose).

    Thanks!

  12. Love this and now, perhaps my 7 year mystery may be solved.

    The big question is…does anyone know how to cure it? If it takes antibiotics, and only those, how in the heck do I convince my doc to give me some? They already think I’m crazy!!!

  13. Unfortunately this study mainly focused on saccharin which as far as I can see is rarely used today. Much more useful would be similiar regarding AceK, aspartame and sugar alcohols. Please redirect me if I’ve missed those studies. Ty,
    Dr B.

  14. What about stevia, specifically NuNaturals liquid stevia (which tastes much less chemical like than other stevia for some reason). Any thoughts on this?

  15. “To determine the effects of NAS on glucose homeostasis, we added commercial formulations of saccharin, sucralose or aspartame to the drinking water of lean 10-week-old C57Bl/6 mice”

    If commercial formulations means they used the saccarin AND the anticaking maltodextrin, then the rats were given the NAS AND maltodextrin. For anyone who doesn’t know, maltodextrin is a simple sugar that could have tampered with the result of these studies.

  16. Gosh, I used sweet and low for a lot of my life in my iced tea. Then I got on the diet coke, thank goodness during my pregnancies it made me sick and couldn’t drink it so my babies didn’t have to digest it. I had no idea. I have so many immune problems, I have so so many food intolerances and I do attribute it do artificial sweeteners and a super low fat diet for many years. I ruined my gut flora for so long and added 2 surgeries. I only use 100% stevia and real maple syrup any other sugar makes me hurt all over my body, same with sweet wine. I sure wish I knew all of this, I am still paying for it.

    • Sounds a lot like me. Have you had the Hydrogen Breath Test? I have both Fructose Malabsorption and Lactose Intolerance. Check out the Low Fodmap Diet – And look up Fructose Malabsorption. Good luck.