Several years ago, I covered the popular artificial sweeteners sucralose, acesulfame-k, aspartame, and saccharin, finding mixed results and little to confirm the widely-held view that they provoke an insulin response. I also wrote about diet soda in general, coming out generally against them while acknowledging the lack of hard evidence either way. But artificial sweeteners may be interfering with our metabolic response to food by an entirely different avenue: the gut biome. According to a new study (PDF) that has nothing at all to do with the cephalic-phase insulin response, artificial sweeteners induce glucose intolerance by altering the composition of our gut microbiota.
There were a few different stages to the study:
1. In mice, adding any of the artificial sweeteners (AS) – the researchers tried saccharin, sucralose, and aspartame – to their drinking water for ten weeks induced glucose intolerance. Mice in the water, water + sucrose, or water + glucose control groups all maintained normal glucose tolerance over the same period. The changes were sweetener-specific, with saccharin having the most pronounced effect.
2. Given previous studies showing alterations to the gut biome with AS consumption, the researchers wondered if these changes were involved with the glucose intolerance. They dosed the mice with various antibiotics. If changes to the gut bacteria were causing or involved with the glucose intolerance, eliminating the bacteria should have an effect. It did; antibiotic treatment abolished the glucose intolerance.
3. To confirm that the microbiota alterations were causing (and not simply associated with) the glucose intolerance, researchers performed fecal transplantations, transferring the gut biome from AS-consuming mice or glucose-consuming control mice into germ-free mice on a regular chow diet. Mice who received a transplant from the AS group developed glucose intolerance; mice receiving a transplant from the control group did not. It was settled, then. Saccharin-induced changes to the microbiota were causing the glucose intolerance.
I hear the cries already: “Ah, but those are just mice, Sisson. I ain’t no mouse and I only have one diet soda a day! Okay, maybe two.” Valid points. Luckily, the study also had a human component.
The last part of the study dealt with human subjects. The participant cohort was non-diabetic, 44% male, and 56% female. Each participant filled out a food frequency questionnaire and underwent various clinical tests to measure glucose tolerance, body weight, waist size, and other indices of metabolic health. Then, researchers scoured the results for connections between artificial sweetener intake (from diet drinks and other sugar-free substitute foods) and metabolic health markers. As it turns out, there were associations between AS intake and increased waist-to-hip ratio (a marker of central obesity), higher body weight, greater glucose intolerance after an oral challenge, higher fasting glucose, and elevated liver enzymes (which might indicate non-alcoholic fatty liver). And when they compared a subgroup of people who ate the most AS to people who ate none at all, the differences were exaggerated.
Okay, but it says it right there: people who ate the most AS were also the fattest. Couldn’t it be reverse causation? In other words: Overweight/obese people are more likely to use artificial sweeteners in an attempt to lose weight. They were already unhealthy and near diabetic to begin with; the AS are just along for the ride. AS consumption could just be a symptom of the obesity and metabolic syndrome. The researchers planned for that, actually, controlling for body weight and finding that the “increase remained significant.”
The researchers then chose a group of participants at random and analyzed their gut bacteria populations. They found that AS consumption in humans predicted certain shifts in the gut biota, similar to the changes seen in AS mice. And when body weight was controlled, the associations remained.
Later, they actually placed seven healthy volunteers who were not habitual AS consumers on a week-long diet containing the FDA’s maximal acceptable daily intake of saccharin. Oral glucose tolerance tests were given before and after the experiment. In 4 of 7 subjects, glucose intolerance worsened after the AS diet; the other three didn’t get worse, but they didn’t improve either.
This isn’t the first paper to show AS-induced disturbances of carbohydrate metabolism. It’s not even the first one to explore the effect of AS on the gut biome. Let’s take a look at some of older evidence supporting this most recent study’s findings.
Second, there’s a wealth of epidemiological evidence linking type 2 diabetes and artificial sweeteners. One study found that daily consumption of diet soda was associated with a 36% greater relative risk of metabolic syndrome and a 67% relative risk of type 2 diabetes. The San Antonio Heart study noted strong associations between diet soda intake and body weight, with the latter increasing in step with the former. And among middle-aged Japanese men, regular consumption of diet soda was linked to a significant increase in type 2 diabetes. Plus, overweight people who drink diet sodas consistently eat more total food/calories than overweight people who drink regular sodas. If the results of this study hold out, those links may be causal, not just correlative.
Third, other studies have found that artificial sweetener consumption can affect the metabolic response to subsequently eating food with actual calories. One small study looked at the effect of sucralose consumption on glucose metabolism in obese patients who don’t have diabetes and don’t use artificial sweeteners on a regular basis. They either drank water or sucralose mixed into water, then drank a glucose solution. If a patient drank sucralose, they released more insulin and their blood glucose spiked higher in response to the glucose drink than patients who drank water. Moreover, sucralose caused insulin to stay elevated longer than water.
Fourth, we’ve known for awhile that artificial sweeteners can affect the gut biome. A famous 2008 paper found that 12 weeks of sucralose had negative effects on the gut bacteria in male rats, including reduced beneficial bacteria, increased fecal pH, and inhibition of pharmaceutical bioavailability.
While the science is far from settled, I think there’s enough that we can start making some decisions about whether or not to consume artificial sweeteners. And this is sweet (pun absolutely intended) vindication for all the people who’ve reported gaining weight or binging or seeing higher postprandial blood glucose spikes after incorporating artificial sweeteners only to be ridiculed for their “anti-scientific beliefs,” their delusions and their conspiracy theories.
Researchers are finally teasing out what many of you have known all along: individuals have individual reactions to artificial sweeteners. What’s good for the lean, CrossFitting goose may not work for the pre-diabetic gander. And it’s probably our highly individualized gut biomes that determine our highly individualized responses to artificial sweeteners.
Lab mice are a homogenous bunch. They live in the same environments, eat the same foods, feel the same stressors, and presumably have very similar gut biota profiles. Everything is controlled. If a dietary change has an effect, it’ll happen across the board. Humans are a bit rangier. We lead different lives from one another. We eat different foods, have different personal and medical histories, carry different microbial auras, and house different microbial populations in our guts. Some of us – and our bacteria – will respond poorly to artificial sweeteners. Some won’t notice a thing. Some will even lose weight.
But if you’re one of the people to respond poorly, if your postprandial blood sugar is getting worse even though the “science” says it’s impossible, you’re not crazy. And you’re not alone.
There’s more to come on this topic. This study was just a preliminary taste, albeit an important one. Stay tuned.
Let’s hear from you guys. What’s been your experience with artificial sweeteners and glucose tolerance?
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About the Author
Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.