Non-nutritive sweeteners (NNS from here on out) can be a very emotionally heated and controversial topic in the health and fitness space.
Die-hards against them will tell you to stay away at all costs, offering such claims that they might foster obesity and destroy gut health. On the opposite side of the spectrum, you may see proponents slamming an energy drink in the morning, a couple diet cokes throughout the day, a scoop of pre-workout, and several scoops of protein powder, resulting in a hefty dose of NNS.
If we were to believe the former camp, where are all the obese bodybuilders? Then again, if we listen to the latter camp, I also think we’re missing a good bit of nuance here.
When we look at NNS, really what we have to determine is: Is there a potential use case for this product for this client, relative to their current health and physiological status quo? This post will help you determine that.
We’re going to be examining the data today around NNS. Here’s a basic summary or layout of the post:
- Intro to artificial/non-nutritive sweeteners – Different kinds, highlighting their different metabolisms
- Health effects: bodyweight effects, metabolic effects like insulin sensitivity and microbiome effects
- Summary and existing questions
- Conclusion and framing on artificial sweeteners vs. sugar in the obesity epidemic today
What we Know:
- When substituted for sugars to reduce energy density of foods and drinks, NNS reduces net energy intake and assists weight management.
- Intervention studies have shown that beverages containing NNS have at least a similar effect on appetite and energy intake to water.
- The collective evidence supports the conclusion that NNS have no adverse effect on blood glucose and insulin regulation in individuals with, and without, diabetes, although more research needs to be done on specific compounds combined with food, as well as looking at responders vs. non-responders (talked about in detail in this post).
- Confounding by adiposity, and reverse causality can explain the positive association between NNS and type 2 diabetes and other cardiometabolic diseases, reported in some observational studies.
- Regarding effects involving the human gut microbiota, data are limited and do not provide adequate evidence that NNS influence gut health at doses relevant to human use, although with the presence of responders vs. non-responders more research needs to be done here as well.
A few existing questions:
- Evaluate responders vs. non-responders in respect to both microbiota and glucose control and what may be going on there.
- Studying NNS in different contexts: hypercaloric vs hypocaloric diets, form of NNS like liquid or solid, NNS consumption with different foods or macronutrients, or studying NNS blends, for example.
- Comparing different demographics of people and assessing effects: Fit and athletic populations, or comparing sexes, different age groups, ethnicities, etc.
Different Types of Artificial Sweeteners
Let’s start with examining a few different types of NNS. I’m referring to them as NNS because as you’ll see here in a minute, some are “artificial” in that they’re synthesized in a lab, while others are natural, or extracted from plants.
In terms of artificial, we have things like sucralose, saccharin, acesulfame potassium, aspartame, and in terms of the natural non-nutritive or low cal: Stevia, monkfruit, and sugar alcohols (xylitol, erythritol, etc).
Not all of these are the same, and each is processed differently in the body, and therefore may have different health effects. Many of the health effects do overlap, but some may have unique effects apart from others that we’ll be discussing as we go along.
For some examples of differences in metabolism, acesulfame potassium is fully absorbed in the small intestine and excreted by the kidneys, so theoretically none of it reaches the large intestine to impact the microbiome there – theoretically, anyway. There are one or two studies that show mild changes which we’ll talk about later.
Some amounts of aspartame and stevia are broken down into separate components BEFORE they get absorbed into the body, and then the smaller components are absorbed, while fully intact molecules that remain travel into the large intestine, so we may have some potential microbiome effects there.
Saccharin also has a bit of absorption, but also some makes it to the large intestine, while others, like sucralose, have no absorption at all, so all of it goes to the large intestine to be excreted later. This is an important point to remember because sucralose is one of the more unique situations we’ll talk about later.
With the above knowledge you might surmise that some of these, like sucralose, are going to be exerting their effects almost all the way through the microbiome (since none is absorbed), while others may be exerting any effects that they have with a mix of being absorbed and by affecting the large intestine’s microbiome.
Bodyfat, Insulin Sensitivity, and Metabolic Health
Let’s go ahead and lead with the elephant in the room here. One of the more well known bits of controversy surrounding NNS are these types of questions: Do they worsen insulin sensitivity? Can they cause bodyfat gain or prevent bodyfat loss?
Many coaches are of the belief that they all destroy insulin sensitivity and you’d be better off consuming a regular coke instead of that diet coke, and on the other end of the spectrum you have fitness enthusiasts and coaches alike downing them at every meal like they’re a foundational dietary staple.
If we look at early data, the idea that artificial sweeteners negatively impacted insulin sensitivity and might increase risk for metabolic disease mostly came from early observational studies, and we know correlation does not equal causation. These are mainly done through surveys asking people how many NNS containing things they’re consuming, i.e. How many diet cokes do you drink per day?
Alot of the original results lack a precise degree of control – Meaning they might be able to be explained by the other components of diet, instead of the NNS. Some people may just switch their regular coke for diet coke, but the rest of their eating patterns are basically the standard american diet. Some might make mental justifications like “Oh well I drank a diet coke with dinner, so I can definitely have those cookies afterwards”.
When we actually look at RCTs and reviews of RCTs, which, remember, are amongst the highest quality of evidence, we mainly see the opposite – That they don’t affect insulin sensitivity and glucose control, except for one or two very interesting studies I’ll be touching on a little bit later.
Bodyweight and BMI
Now that we know they don’t affect insulin sensitivity on the whole, let’s take a look at BMI. Yes, BMI has some serious limitations, and is basically useless amongst fit and athletic folks with above average muscle mass. On the population level, however, where the vast majority of individuals are overweight and undermuscled, BMI can still be a useful tool.
First let’s take a look at a systematic review on over 13,000 pieces of data that were collected from 56 studies, with about half of them being observational, and the other half being RCTs. The results were simple: NNS did not increase body fat. In fact, many trials show a decrease in body weight when compared to consuming water. This could be because artificial sweeteners and carbonated beverages help to enhance satiety and maybe help with hunger and cravings.
Next we have a review study solely on RCTS, so a higher level of evidence. 20 RCTs were included with about 3000 participants. The main thing they looked at was BMI/bodyweight reduction, which can be a sort of proxy of glucose control because we know if glucose control got worse, bodyweight probably wouldn’t come down.
Some of the studies controlled energy intake – Meaning they were calorie restricted, whereas others had folks that were previously consuming mostly sugar-containing drinks switch to diet drinks but left the rest of their diet unrestricted.
Here’s a quote from the study; the results are pretty clear: “When comparing non-nutritive sweeteners (NNS) vs sucrose, significant weight/BMI differences appeared favoring NNS. Consumption of NNS led to significantly reduced weight/BMI differences in unrestricted energy diets, but not in calorie-controlled weight-reduction diets. Participants with obesity and adults showed significant favorable weight/BMI differences with NNS. Data suggest that replacing sugar with NNS leads to weight reduction, particularly in participants with overweight/obesity under an unrestricted diet.”
“… particularly in participants with overweight/obesity under an unrestricted diet” – This is going to be the majority of Americans. Yet another data point for the favorable use of non-nutritive sweeteners.
Insulin Sensitivity and Metabolic Health
Now that the bodyweight piece has been settled, let’s look a bit deeper at glucose control and insulin sensitivity. There’s a great, newer 2021 review that looks at 25 randomized RCTS in humans specifically looking at glucose control – They included studies on stevia, aspartame, acesulfame potassium, saccharin, and sucralose.
As far as duration, the studies ranged from being acute in nature all the way up to 18 weeks. 23 out of the 25 studies found no significant differences in glucose levels or insulin sensitivity compared with a control, so for the most part, there were no differences at all. But we need to talk about those last two studies and an additional study not included in this review.
The Outlier Studies
When you’re doing an RCT, you want to minimize the variables as much as possible, so in general, when there’s a treatment arm with a NNS, it’s generally ONLY the sweetener consumed without the presence of other food or compounds versus whatever control they’re using, which is also consumed without anything else.
Interestingly, the 2 RCT’s that found a decrease in insulin sensitivity had a treatment arm where they combined sucralose with maltodextrin at the same time, so the NNS and a carb source.
One study saw an 18% decrease in insulin sensitivity, while the other study didn’t report an exact % decrease, but did see higher insulin levels and glucose levels at the studies end. Quite interesting, and to further this, we’ll take a look at a very well done RCT that is NOT included in this review study that looks at sucralose and maltodextrin that shows the same thing – So we have 3 RCTs to my knowledge that sucralose paired with calories or carbs may impact insulin sensitivity negatively.
In the study that wasn’t included in that review, they actually did parallel studies, one in adolescents and one in adults. There were three treatments compared – sucralose beverage only, sugar beverage only, and sucralose plus maltodextrin. It lasted two weeks. They looked at insulin sensitivity as well as MRI imaging of the brain to look at the brain response to sweet taste perception.
The reason they did this is because if there was a decreased response to the sweet taste perception in the brain, this could potentially cause people to consume more sweet things potentially containing sugar, because they don’t get enough of the brain response indicating “this is enough sweetness”.
The results: In the sucralose only and sugar only groups, there was no difference in insulin sensitivity and postprandial glucose levels after an oral glucose tolerance test at the end of the study.
However, when sucralose was consumed with maltodextrin, insulin resistance and therefore higher glucose levels was observed at the end of the 2 weeks, along with a decreased brain response to sweet taste, which was also not found in sucralose alone or sugar alone.
In the adolescent study, the effect was so strong that the researchers discontinued that part of the study halfway through because they found it unethical to continue.
Why Might Co-Consumption of Carb + Sucralose Worsen Insulin Sensitivity?
These results may be through microbiome effects, but it’s also been observed that sucralose transiently increases the amount of glucose transporters in the intestine, which may mean that glucose gets absorbed significantly more rapidly when combined with sucralose – And the quicker you absorb glucose, the faster your glucose levels rise, and the higher the spike you have.
All in all, the weight of the evidence indicates decreases in BMI and no effect on insulin sensitivity, but I think this is a really interesting line of research that needs to be explored more – combining non nutritive sweeteners with other foods in studies to see what happens.
However, the majority of people reading this post probably have all their health and fitness ducks in a row so to speak, and are most likely pretty insulin sensitive to begin with. The question here is would it affect this population the same way?
We don’t know; it’s hard to tell. In all honesty, it’s probably fine to consume with carbs/food every now and then, but if you want to hedge your bets and be quite careful – Consume that sucralose-sweetened 0 calorie beverage at least an hour apart from other foods.
Effects on the Microbiome
One of the bigger claims within the space is that they negatively affect the microbiome. When most people hear the word “microbiome” they instantly think of the gut – But there are other microbiomes on our body too! So let’s start out with our mouths.
This is good news to your dental hygiene and I’m sure dentists out there will appreciate this, but most NNS has positive effects on the oral microbiome, reducing cavity-associated bacteria populations in the mouth. Sucralose actually has this effect the strongest followed closely behind by stevia; preventing deleterious bacteria from growing. But since it’s quite obvious they have bacteria-altering properties in the mouth, it would follow they’re also altering things in the gut.
I’m going to give you a bit of perspective on the body of research concerning artificial sweeteners and the microbiome. It’s important to understand this to evaluate future studies you may hear of that might be trying to fear-monger you.
When you’re going through the entire body of artificial sweetener/microbiome literature, nearly every study you open is “In mice, this happens..” and “In rats, that happens…” and then a ton of cell culture and even computer model prediction studies, which is called “in silico” in studies. A lot of these studies do not indicate they’re mouse or animal studies in the title, either.
The data in mice is extremely compelling. We can do tons of things to mice, including easily taking samples from the interior of their actual intestines to see actual composition within, instead of just going off of fecal samples.
We can make mice completely germ-free, meaning they don’t have a microbiome at all, and then do microbiota transplants from another mouse to assess health effects. There’s just a lot more we can do to study these things that aren’t available to do at the moment in humans, or not available to do ethically, easily, or inexpensively.
Effects in Animals
In mice you see things like NNS increasing the Firmicutes to Bacteroidetes ratio, which is a more obesogenic ratio. We can easily induce experimental insulin resistance and metabolic issues by giving certain artificial sweeteners like saccharin and sucralose, and we can transmit those microbiomes to germ-free mice and they develop the same metabolic issues, so its confirmed in mice that the microbiome is eliciting these metabolic effects.
We see reduced short chain fatty acid production, which are normally gut-protective, we see increases in inflammatory molecules like quinolinic acid, and we see decreases in molecules that normally suppress reactive oxygen species.
Basically, if you were a mouse and you were reading those studies, you should be scared. If we were all mice in a country of mice, these things would certainly come with warnings about all the terrible effects they cause and maybe even outlawed.
However, surprise: We’re not mice or rats. So this huge body of literature may not even apply to us, and spoiler alert: the vast majority of it doesn’t seem to.
In humans, we have important end-measures and health outcomes, so even if these bacterial changes are occurring, then they’re not having even close to the same effects in humans that they are in mice.
Couple that with the fact that it’s really hard to assess accurate microbial changes throughout the gut in humans. Most of the human microbiome studies go off fecal samples, which may only give a decent representation of the microbiome at the end of the colon, missing out on the proximal intestine. Fecal short chain fatty acid levels also do not exemplify the amount of short chain fatty acids produced in the intestine. Short chain fatty acids are largely absorbed in the intestine by a tightly regulated mechanism. So we can see the amount of limitations on human microbiome studies. All that said, however, if we filter out the stuff that may not matter as much, we still do have some things to talk about.
Effects in Humans
So far, in humans, we can see that acesulfame potassium, saccharin, sucralose, and stevia affect the microbiome composition of humans. The interesting thing about more emerging research is that there seems to be “responders” and “non-responders” to changes in microbiome and glucose homeostasis for a couple of these. We’ll talk more about that in a bit.
Ace K – At the time of a 2020 review, only two studies had shown alterations in the microbiome of humans with Ace K; there was a bit of reduced overall diversity, but these were deemed to be non-functional changes.
Saccharin – Saccharin is one of those that has been shown to have responders and non-responders, but this has only been specifically highlighted by one 2014 study which had 7 study subjects who did not regularly consume artificial sweeteners. 4 out of the 7 subjects had significant changes in microbiome status, and the same 4 had altered glucose homeostasis. I would question this, because since then, significantly more human trials have come out showing no changes in the microbiome and no alterations in glucose tolerance.
However, something to consider is that these studies have larger sample sizes than the first one I talked about, and all studies report average results. Studies aren’t obligated to report on outliers or individual responses. It’s possible there could have been a few outliers in these other studies that were “responders” or had altered microbiomes and glucose homeostasis, but on the whole, the majority did not, so there was no statistically significant changes.
Sucralose – Another NNS that has more recently shown to have responders and non-responders. For example, a 2019 study tested 34 volunteers, comparing sucralose capsules to control over 7 days. On the whole, they report glycemic control and insulin resistance were not affected during the 7-d period. At the phylum level, the gut microbiome was not modified in any group. However, this study also chose to highlight outliers – There were responders who had higher firmicutes and lower bacteroidetes after the study, and these people did have a higher glycemic and insulin response after the study was completed as well. Even though the authors of this study conclude that there are “no significant changes in glycemic control and insulin resistance” because the majority did not have that occur, they also conclude that there needs to be significantly more research specifically into the area of responders vs. non-responders and what could be going on there, because as of this moment we have no idea why this is happening.
Stevia – The only study we have looking at stevia and human microbiome doesn’t have the most powerful design. Different extracts of stevia were basically incubated with bacterial populations from the poop of healthy volunteers and then the changes were assessed, so in other words we’re not actually looking at stevia that was consumed by people.
There were changes in the microbial populations, but they were deemed non-functional and neutral. Not to mention that stevia has been identified in other studies to have numerous other beneficial effects across the body: It may actually help with insulin sensitivity, and it has anti-cavity, antioxidant, anti-hypertensive, anti-inflammatory and antitumor activities.
A note on IBS and Gut Health
You’ve probably heard from many gut gurus to avoid artificial sweeteners when IBS is present. Interestingly, there are nearly no human studies looking at artificial sweeteners and IBS or other gut issues. There’s a plethora of cell culture and mouse data on intestinal permeability, IBS, etc, but these have not been replicated in humans.
We do have numerous anecdotes in the health space about discontinuing artificial sweeteners and IBS symptoms residing, and avoiding artificial sweeteners is still considered to be part of an elimination protocol for IBS/SIBO/etc by most gut health experts, but human data specifically looking at artificial sweeteners and IBS outcomes aren’t there.
The sentiment is more along the lines of, “Okay, we know artificial sweeteners may impact the microbiome, and we know changes in the microbiome happen in IBS, sooo…” A lot of the studies use this logic. If you have gut issues, it might still be good to minimize or avoid these, but I just wanted to let you know human data here is very scarce.
As you can see, on the whole, non nutritive sweeteners can certainly act as a viable sugar substitute and have positive effects in most populations or individuals.
A lot of people will focus in on the tiny details or very small negative changes that might occur, but in the age of the obesity epidemic, I can guarantee you if every single obese person in America right now switched out ALL sugar for non nutritive sweeteners, we’d see reductions in obesity and weight loss.
Yes, there are some things that still need to be worked out and potentially to be careful about, like that study with sucralose combined with maltodextrin altering insulin sensitivity, and the non-responders vs. responders. However, as far as the literature goes so far, the great benefits that NNS’ have in potential weight reduction when substituting for sugar far outweighs any small evils that may be present there, especially in today’s age of obesity.
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