Aidan:
Hello, and welcome to the Ideal Nutrition Podcast. My name is Aidan Muir, and I’m here with my co-host Leah Higl. This is episode 114, where we are going to be talking about whether artificial sweeteners raise insulin or impact blood glucose levels. To be clear about what we are talking about in this episode, we are specifically talking about artificial sweeteners. I always give that clarification to be like, we’re not talking about natural sweeteners such as stevia, although there is a lot of overlap. We’re also not talking about sugar alcohols, which should be a completely separate topic, partly also because a lot of sugar alcohols, not all, but a lot of them also contain calories, which should put them in a separate category. We’re going to be going through whether it raises insulin, and blood glucose levels and if so, how much that would matter as well.
Leah:
First thing we’re going to start off by talking about is more in regards to the mechanisms or proposed mechanisms that go along with this topic from both an acute, and chronic perspective. Looking at the acute mechanisms, one example of the logic that we see quite often, and also in one particular paper that we will link in the show notes is that the ingestion of artificial sweeteners results in the release of insulin from the pancreas due to the sweet taste of the sweetener being mistaken for glucose. This increases the levels of insulin in the blood, eventually leading to decreased receptor activity due to insulin resistance. This logic stems from a known mechanism called the cephalic phase insulin response, and this is basically where there is oral exposure of sugar or carbohydrates that triggers an early low-level rise in insulin.
Aidan:
Yeah. Basically, even before glucose levels are raising in the blood, insulin is already released. When you think about it, that’s not actually that absurd to think if anything sweet consumed leads to that response, that mechanism doesn’t seem too wild when you think of it like that.
Leah:
The logic makes sense, so I can see where that mechanism or proposed theory comes from, because we know that our body does do this thing, where there are receptors orally, it does have a certain response on insulin, so that is something that does exist. But that is just a mechanistic theory like, that is going to be… Obviously, we always talk about mechanisms versus outcomes in the literature and how… Maybe they don’t always line up or maybe they do, but they are separate things in discussing them. That is just a mechanistic theory, and we will go over research actually assessing the outcomes on both blood glucose levels, and insulin from the intake of artificial sweeteners. However, there are some things to briefly consider when talking about this topic and I think one of the more interesting ones is, if somebody’s insulin was raised from having a non-calorie, non-glucose containing sweetener, would this lead to a hypo, because you have the presence of insulin but not the presence of glycogen coming or glucose coming in?
Aidan:
Specifically, if glycogen levels were low to start off, if you had low levels of glycogen, so you didn’t have this reserve of glycogen or anything like that, insulin raised and there’s not much glucose available under those circumstances, would this lead to a hypo? And then the next thought process on that is, is it dose-dependent? If that were to be true, for example, if one can of Coke led to a meaningful increase in insulin, which could be a risk if somebody was in this low glycogen state, what would five cans of Coke do? If we had more of these artificial screeners, would it lead to a bigger outcome that could potentially be more dangerous? One thing that we don’t see is we don’t see that.
Leah:
We don’t see people going into hypos from having cans of soft drink, because that is a very dangerous thing. The symptoms are very clear of a hypo. It is something that will land you in hospital, and we know that we don’t really see those outcomes occurring.
Aidan:
Yeah. If we’re looking at that cephalic phase response, that mechanism can be ruled out, because we don’t see these hypos or anything like that occurring. The only way that this mechanism would potentially even be possible is if blood glucose levels also increase for some mechanism as well, alongside the artificial sweeteners too. Yeah. Those are chronic mechanisms, because that was very short-term focus. Looking at the chronic mechanisms, it is a little bit more complex. But one example that you touched on at the start there was that if somebody did have increased levels of insulin in the blood… This was part of that logic that you referred to at the start. If somebody did have increased levels of insulin in the blood for a long period of time, that theoretically could lead to a decrease in receptor activity. This theory that some people were pointing to is like, what if somebody had artificial sweat every day that led to an increase in insulin every single day, and then that led to an increase in insulin resistance, because of this decrease in receptor activity.
The quick rebuttal to that is that high insulin levels don’t necessarily cause insulin resistance. That is a very complex thing that I’ve really simplified down. But to provide a bit of evidence for what I’m saying when I say that, because it is a nuanced topic, is we don’t really see high carbohydrate intake as an isolated variable being linked to diabetes. What I mean by that is, if there’s massive amounts of people, and half of them get put into a higher-carbohydrate group, the other half get put into a lower-carbohydrate group, but the same total calorie intake, so they have more fat most likely, the same body weight, the same exercise levels, the same age, the same everything else, we see similar rates of the progression of diabetes. It’s not like higher carbohydrates leading to higher insulin leading to diabetes. It’s a much more complex thing than that.
That’s another fact that I’ve been like, even if it did increase insulin, does that necessarily mean it’s going to increase insulin resistance down the line? There’s a lot more variables that matter significantly more in that kind of argument. But another mechanism that’s a bit more complicated than even that is the microbiome stuff. If artificial sweeteners change the gut microbiome, that could play a role in insulin resistance, if these bacteria happen to be more associated with insulin resistance, and everything like that. That’s more complex than what I want to talk about now, but we’ll probably cover that later too.
Leah:
Moving on to looking more at the outcomes rather than just the potential mechanisms and the theory, we’re going to go through a few studies. I’m going to start off with looking at ones that have shown a difference from an acute perspective, because there is a small handful that have shown a difference in blood glucose levels, and insulin. There was some small scale research. One example of this is a 2013 study, where they gave 17 subjects either water or sucralose prior to an oral glucose tolerance test, and that was in a crossover design. Basically, what they found is that blood glucose levels increase slightly more after the sucralose, then the water, so 4.8 millimoles for the sucralose compared to 4.2 for the water. And then they also found that insulin was around 20% higher after the ingestion of the sucralose.
Aidan:
That was an increase of 4.8 versus 4.2 as well, so they might’ve started like five, just for context in terms of how higher it would go. That study is not an isolated study. We have seen other examples of this. I once saw a doctor on TV do an example of one day they had just soft drink by itself, the equivalent of a can of soft drink, or it was actually an oral glucose tolerance test, so they had the 75 grams of carbohydrate by itself. And then the next day they came back and did the test, but they had a front load of sucralose before that, and they measured their blood glucose levels, and the second day it went higher than the first day.
Leah:
Yeah, it’s interesting.
Aidan:
It does seem interesting, and we’ll talk about larger sample size stuff, but there’s many reasons we wouldn’t read too much into that, although it does make a compelling argument when you see that like that.
Leah:
When you see that data you’re like, “Mm-hmm. There is some data suggesting there may be something happening here, and we’ll go onto more larger-scale research.” But there is this stuff out there. I think one thing that you noted in the notes is that you personally wouldn’t read into it too much, just because of the small sample size, and also the fact that blood glucose levels do fluctuate a lot. Looking at a small sample size, there may just be differences in the groups, just based off the fact that blood glucose levels fluctuate normally a lot.
Aidan:
Yeah. At least with that first study versus the doctor example, in that doctor example, you could be like, “What if just repeating the test would’ve changed it anyway, at least in that first study there was a crossover design?” When certain scientists have looked at this, and tried to explain why this happens, people have talked about that cephalic phase response and everything like that. But if that’s true, why do blood glucose levels also theoretically increase alongside that? Going back to the sample size issue, because blood glucose levels do just fluctuate, I truly believe that you could redo that test, and use placebo versus placebo, and you’ll see a difference.
Leah:
You’ll see a difference between the two?
Aidan:
Yeah. I was even just, earlier today, reading some research about zinc lozenges and the effect of like, do they make it so that illness duration is shorter? Fun fact is inconclusive, it’s a bit all over the place. But there’s multiple studies that you’ll see cited that are showing that it does shorten the duration. But then there’s one rogue like 1984 or 1987 study that basically said it extended the duration by five days, people’s duration of illness went from seven days to 12 days. It’s like if you only saw that one study in isolation with that small sample size, you would think that having a zinc lozenge was bad.
Leah:
It wasn’t going to be bad for you. Yeah.
Aidan:
Whereas if you looked at these other three studies that showed positive, you would be like, “Oh, this is a really helpful thing.” You put it all together, and it just looks really mixed.
Leah:
Yeah. I think moving on to research finding no impact on insulin or blood glucose levels, because there does seem to be a bit more there, one smaller study where there was 22 subjects trialing 400 milligrams of aspartame, 135 milligrams of saccharin or an unsweetened drink, and that level of aspartame and saccharin is the normal amount in a soda, or any artificially sweetened beverage, so it’s an equivalent. There was no difference in insulin, or blood glucose levels found. Looking at something a little bit more compelling and getting past that sample size issue, there was a 2020 systematic review involving 26 studies, so it’s usually a lot better than one, and including thousands of participants. That found no acute difference in blood glucose levels or insulin, overall.
Aidan:
Yeah. I think that’s a pretty big nail in the coffin for the acute stuff, just being like if you get average person, get them to have a can of diet soft drink, it’s probably not doing anything to their blood glucose levels or insulin. This even makes sense, looking mechanistically at stuff like aspartame. If you have aspartame, it breaks down into the aspartic acid, and phenylalanine, and there’s a byproduct of methanol which comes alongside that. But the amount of aspartame is such a small amount, this is like a 100 times sweeter than sugar. It might even be a little bit more than that, which means it’s a very, very tiny amount that’s used in these products, like those numbers you talked about that like 400 milligrams. The aspartic acid, and phenylalanine are amino acids, and they’re just in such tiny amounts. If we’re thinking about amino acids in the context of a lot of people having over 100 grams of protein per day, and we’re looking at these 200 milligram amounts of these amino acids.
It’s really nothing. The methanol thing people might be more concerned about, but there’s this more methanol in a tomato than there is in… It’s these tiny amounts of things. Yeah. When you think of it like that, you’re like, “Okay. How would this be spiking blood glucose levels or anything like that, apart from mechanisms like the cephalic response in relation to the sweet taste and everything?” Going onto that more complex area of the gut microbiome, the obvious logic here is that theoretically, regular use of artificial sweeteners could change the balance of our gut bacteria, and this could make our cells resistant to the insulin that we produce, leading to both increased blood sugar and insulin levels, over time. That logic doesn’t seem too farfetched. If it was changing the gut microbiome, then we could see that, potentially, that is a reasonable piece of logic. There was a 2020 study that had 120 participants who consumed very high dosages of artificial sweeteners including saccharin every day for two weeks, and they found some changes in the microbiome via stool samples.
Keep in mind that stool samples aren’t 100% perfect, because that’s what is excreted, not necessarily what is in our microbiome. But it’s one of the best simple ways we have of testing things, and they found that it looks like there was some impaired glucose tolerance. Although multiple sweeteners were tested in that study, saccharin was the one that had the largest difference. They also did specify that the dosage used was lower than what had been considered acceptable daily intake, even though it was higher than what we’d normally consider a normal intake. I don’t think this is common knowledge, but saccharin’s acceptable daily intake is really low in comparison to other artificial sweeteners. Everybody’s heard people talk about how the acceptable daily intake of aspartame is the equivalent of 21 cans of Diet Coke.
Leah:
Just a ridiculous amount.
Aidan:
Ridiculous amount, and people give different numbers, right? But it’s a really high amount. The acceptable daily intake for saccharin is 3.7 cans. It’s the equivalent of 3.7 cans of diet soft drink. It’s actually quite low. When I give these guidelines, artificial sweeteners are safe when used in normal amounts and stuff like that. When you put it into that context, the normal amount for something like aspartame, you’ve got a big margin.
It is quite low, and the combination… I should mention that that study that I was talking about, where they did see these changes in glucose tolerance and also the microbiome, they used less than that 3.7 which I touched on, so it’s like there, even below the acceptable daily intake, this study did notice some changes. But once again, I wouldn’t read too much into that, because the entire body of evidence hasn’t consistently had findings like that.
We also have saccharine studies that haven’t found changes in glucose tolerance too, so it’s not this clear-cut thing, but studies like that one, and the acceptable daily intake being so low is part of why saccharin has lost popularity. Even though I’m talking about this, in Australia, saccharin is not very popular. In the US, there’s a sweetener called Sweet’N Low, which is the equivalent of table sugar. It’s one of their alternatives, basically. Even that’s lost a lot of popularity. I was on ChatGPT earlier being like, “What products in Australia use saccharin?” It listed a few things like Pepsi Max, Diet Coke, and Diet Lemonade was another one from Schweppes. But when you look at those, they actually, those don’t even contain saccharin as well. I don’t know if it’s just because ChatGPT was like, it’s only able to go up until about 2021.
Leah:
Really outdated.
Aidan:
Yeah. But saccharin in Australia is sweetener 954, so that’s something to look for on labels and those products don’t contain it. It’s a very rare thing. I think it’s useful to know, and be aware of sweetener 954, but it’s also not really heavily in our food supply, and this is largely a factor why. In terms of stuff that we have evidence for changing our microbiome, as I talked about with aspartame, even mechanistically, it wouldn’t really make sense for it to do that, because it’s so small of these common things that we’re consuming through food anyway. But sucralose, and saccharin, obviously, as we’ve talked about, have a little bit of evidence for altering the microbiome.
On the one hand, it seems that this is unlikely to have a large impact, because when we look at a lot of long-term very controlled data, we don’t really see much of a link with many health outcomes and artificial sweeteners. We do, in a lot of uncontrolled research though. But if it was having a huge impact with the microbiome stuff, we’d probably see more of an impact. But I also wouldn’t completely rule out any level of impact whatsoever either, so I have a bit of an open mind on that kind of thing, which is why I say the microbiome stuff is a bit complex too.
Leah:
Yeah. I think, in any regard, the microbiome stuff is always really complex under any topic. But just as a little bit of summary for this episode, so artificial sweeteners definitely do not impact blood glucose levels or insulin in the short-term. I think that’s pretty safe to say, or at least it doesn’t do it to a significant level that we can see, and that can be said with a fair amount of confidence. The longer-term stuff, however, is a little less clear. It’s unlikely to have a large impact if at all, since otherwise, we would see different outcomes in that 2021 systematic review. But we’re both not saying 100% confidence, there is definitely zero impact at this point, because we’d like to see more research, we’d like to see what the outcomes of that are. There’s definitely more to be investigated there, but I would say that I’m not giving it up just yet.
Aidan:
This has been episode 114. As always, if you could please leave a rating or review, that would be massively appreciated.