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Hey everybody, Mikki here. You're listening to another mini mikkipedia on a Monday. And today I want to chat about aspartame, insulin, and weight loss, and what the science actually shows. Now, this has been inspired by Dr. Lane Norton's podcast a couple of weeks ago, which I sometimes go into. He does some pretty good breakdowns, and this was quite a detailed breakdown he did on this meta-analysis. And I thought, well, an hour is quite a long time to listen to this.

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which is what Lane's podcast was. I really appreciated it. But I did just want to pull out some of the highlights for you, for anyone who is interested in this topic, and many people are. And I will say that this is one of the most controversial topics in nutrition, that of artificial sweeteners, particularly aspartame. And a lot of very smart people have varying opinions. One of the narratives that you'll hear is something like this. Artificial sweeteners trick your brain. Your body tastes something sweet.

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It releases insulin, but there's no sugar coming in. And this makes you hungrier, causes you to overeat, disrupts your metabolism, and ultimately makes you gain weight. Plus, artificial sweeteners like aspartame might cause cancer, cardiovascular disease, and type 2 diabetes. And it does sound pretty compelling. And I do have a lot of people who completely avoid diet drinks or sugar-free foods because of these concerns. And I completely understand why.

01:31
In addition to that, they may choose a full sugared variety over the artificial sweetener because of the potential for harm. But one of the first things to talk about, which we will, is that this narrative is built largely on observational studies in rodent research using absurdly high doses. When we look at what actually happens in human randomized controlled trials, which is the gold standard of research, we see a really different picture. And

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Today we're going to go through a comprehensive meta-analysis which was published in the Advances in Nutrition that analyzed over 100 human studies on aspartame specifically. We're going to look at what happens to your blood glucose, your insulin levels and your hunger hormones and your actual calorie intake when you consume aspartame. And what I will say is that the findings are quite different from what you might see on social media. So let's start with the basics of what is aspartame.

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because understanding what aspartame actually is will help us understand why the concerns about it don't really hold up physiologically. Aspartame is what's called a low calorie sweetener. It isn't no calorie, as it technically has four calories per gram, which is the exact same as sugar, but it is 200 times sweeter than sugar gram for gram. And because it is so much sweeter, you need such tiny amounts that beverages can essentially be

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you know, zero calories. So a 355 ml can of Diet Coke contains 184 mg of aspartame, and that's about 0.74 calories. Compare that to a regular Coke, which has about 140 calories, which is around 200 times more calories than the Diet Coke, which makes sense given the sweetness difference. Now, aspartame is made up of two amino acids, aspartic acid and phenylalanine.

03:23
with a methyl ester group attached. And here's a critical point that you need to be mindful of, is that aspartame doesn't enter your bloodstream intact. It never gets to your tissues as aspartame. Instead, it rapidly and completely is broken down in our GI tract before it's even absorbed into those three components. That's 50 % phenylalanine, 40 % aspartic acid, and 10 % methanol.

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This is crucial to understand because it means that any effects from aspartame must come from these breakdown products, not from the aspartame itself. And as we'll discuss, these breakdown products are found in much higher amounts in regular foods, especially protein sources and fruits. So let's discuss the insulin hypothesis. This is a theory that's been driving the fear around artificial sweeteners. I want you to understand the logic because it does sound reasonable at first.

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So the claimed mechanism is you consume something sweet tasting, your brain detects that taste, your brain anticipates glucose coming in, and in anticipation, your pancreas releases insulin. This is the sivalic phase insulin response. This is typical. But with the SPA team, there's no actual glucose coming into your bloodstream. This insulin spike without glucose makes your blood sugar drop. Low blood sugar triggers intense hunger. You overeat to compensate.

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and those extra calories make you gain weight. Over time, the repeated insulin secretion leads to insulin resistance, and insulin resistance progresses to type 2 diabetes. So these are the proposed mechanisms, and it does sound logical. However, it doesn't match what happens in human studies. And if you think about it from a basic physiology standpoint, this theory has a fatal flaw. If aspartame triggered significant insulin release without providing glucose,

05:15
People would go into a hypoglycemic state every single time they drank a diet soda. That doesn't happen to me. Or you, probably. Or anyone that I've talked to. They'd feel shaky, dizzy, and confused, which are classic symptoms of low blood sugar. The only way this theory could work without causing hypoglycemia is if the insulin response was offset by an equal and opposite glucagon response. Glucagon is the hormone that raises blood sugar.

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But if that's happening, then you don't need to worry about insulin because glucagon is countering all of its effects. So let's look at what the research shows. This meta-analysis from advances in nutrition is pretty robust. So typically a meta-analysis is when researchers take multiple studies looking at similar questions and statistically combine them to get an overall answer. It's more powerful than any single study because you're pulling data from hundreds or thousands of participants.

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And this review is particularly strong because the inclusion criteria was really specific. They only used human studies. They only use those randomized controlled trials. So they were gold standard. They weren't observational. They used any age, any sex, any ethnicity and BMI. And they included people with type 2 diabetes, type 1 diabetes or pre-diabetes. And they excluded people with other chronic diseases to avoid confounding.

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They looked at studies using aspartame in any form, in water, as part of beverages, combined with food, in tablets, at any dose, and whether consumed once or repeatedly. They analyzed 101 studies in total, conducted four separate meta-analyses on acute responses, and systematically reviewed medium and long-term studies. And this is important because if we're discussing what the research shows,

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Again, appreciation, this isn't talking about just one cherry-picked study. It's talking about a consensus from over 100 human trials. Essentially, let's start with the blood glucose responses that the meta-analysis found, because it is fundamental. If aspartame affects your metabolism negatively, we should see changes in blood glucose. And when they compared in the first meta-analysis, aspartame alone versus a control, such as water, they found no effect on blood.

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on blood glucose, meaning aspartame by itself doesn't raise or lower your blood sugar. When comparing aspartame to other low calorie sweeteners like stevia or monk fruit, they found no difference in blood glucose, meaning that these non-nutritive sweeteners all behave similarly. There is no glucose impact. Now, when they compared aspartame to actual sugars and carbohydrates, obviously there were differences, but this does tell us something important. When aspartame was

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compared against sweet tasting carbohydrates, you got a significantly lower blood glucose response with aspartame. And the effect size was large, meaning there's a clinically meaningful change in blood glucose with sugar compared to aspartame alone. And the reason for this is quite clear is because aspartame doesn't contain glucose, or the sugars do. Now, when they compared aspartame against other non-sweet carbohydrates,

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they found again significantly lower blood glucose with aspartame and the effect size was also large. And this is for the same reason that aspartame doesn't provide glucose, which is the byproduct of all carbohydrate foods. And when they compared aspartame versus mixed meals or meals that had other nutritive components like other proteins and fats, they found significantly lower blood glucose with aspartame and the effect size was large. Now, when they looked at

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aspartame versus food alone, so they looked at just food or aspartame with food, they wanted to address the question, does aspartame change how your body handles carbohydrates when they're consumed together? And when they compared food and aspartame versus the same food alone, there was no difference in blood glucose response, which means that adding aspartame to food doesn't change how your body processes that food's carbohydrate. And when comparing food and aspartame versus food and sugar,

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you got a lower blood glucose with the aspartame version. And that's because you're taking away, when they compared a food and aspartame to food and sugar, they got a lower blood glucose response with the aspartame version. And that is because they subtracted that sugar's glucose load. So the takeaway is clear. Aspartame is metabolically inert when it comes to blood glucose. It doesn't raise it, it doesn't lower it, it doesn't change how your body.

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handles actual carbohydrates. Now what about insulin? Again, they did another meta-analysis looking at insulin response to aspartame alone. And when they compared aspartame to placebo, they found no effect on blood insulin, which meant that in the human clinical trials, aspartame does not trigger insulin release. So therefore, we can say the supposed mechanism driving all the metabolic harm doesn't actually exist.

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When comparing aspartame to sweet tasting sugars, you found as expected aspartame produced far lower insulin responses because sugars naturally trigger insulin while aspartame does not. And this was at a large effect size. When they compared aspartame to non-sweet tasting carbohydrates, you got the same response. Lower insulin with aspartame because carbohydrates trigger insulin as part of a normal glucose metabolism and aspartame does not.

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And when comparing aspartame to other nutritive components like meals, again you got a much lower insulin response with aspartame. Now here is something interesting that did come up. When they compared aspartame to other low calorie sweeteners like stevia or monk fruit, there was a slightly higher insulin level with aspartame. And this is important. The sub analysis only included four studies. The difference was very small and aspartame still didn't increase insulin compared to baseline. And this...

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Interpretation could be just due to random chance because of a small sample, or it might be that stevia in monk fruit might actually slightly decrease insulin, which would be interesting. We know this can happen with allulose, but the key point here was that aspartame alone still showed no insulin increase versus placebo. And then their fourth and final meta-analyses was aspartame combined with food. So what happens to insulin here? When you combine food and aspartame versus the food alone,

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No difference in insulin. When you looked at food in aspartame versus food with other low calorie sweeteners, there was no difference in insulin. And this in fact contradicts that small finding I just mentioned from meta-analysis three. So potentially suggesting that that was a finding due to chance with regards to stevia and monk fruits effect on insulin. When they looked at food plus aspartame and food plus sugars, you got a significantly lower insulin with aspartame.

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And then finally, when you got looked at food in aspartame versus food and other carbohydrates, again, you got that lower insulin response with aspartame. So really this whole meta analysis found that the mechanism that supposedly makes aspartame metabolically harmful, treating insulin without providing glucose, simply doesn't happen in human studies. So if aspartame doesn't spike insulin,

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What about the claim that it makes you hungrier and causes you to overeat? And this is really interesting for anyone concerned with weight management. When you're comparing a Spartame to placebo or other low calorie sweeteners, there is no difference in subjective appetite ratings. There's no difference in energy intake or the total calories consumed. And when comparing a Spartame to sugar or nutritive components, you get better appetite control with a Spartame and lower total energy intake with a Spartame.

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Interestingly, several studies have compared aspartame sweetened beverages to plain water as a replacement for sugar sweetened beverages. And the aspartame group often reported less hunger than the water group, consumed fewer total calories than the water group, and lost more weight than the water group. And the most likely explanation for why aspartame sweetened beverages would perform better than water is that the

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Sweet taste provides satisfaction that helps people avoid seeking that sweetness elsewhere. If you're just drinking water, you might end up finding cookies or other sweet foods later. The aspartame sweetened beverage gives you that sweet taste without the calories. It doesn't appear in that randomized controlled trial level to initiate more cravings for sweet food. They also looked at appetite regulating hormones like GLP-1,

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GIP, is glucose-dependent insulin tropic peptide, glucagon, and leptin. And the findings were really consistent. Few to no effects on these hormones. In the case where there were changes, they were generally in a favorable direction, like an increased GLP-1 response, which as you should know, by now, given all of the talk of GLP-1s, this does suppress appetite. And they also looked at some medium or long-term responses.

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The responses I just went through were acute responses. And these medium-term studies are over two to 30 days. The results were pretty much exactly the same. And the researchers looked at studies with a daily aspartame intake ranging from 15 to 45 milligrams per kilogram of body weight. To put that into perspective, for someone who weighs around 80 kilograms, that's equivalent to about seven to 20 diet cokes per day, which is well above

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what most people would consume. There were no effects on blood glucose, insulin, no increase in adverse events compared to placebo. These were consistent in both healthy people and those people with type 2 diabetes. And there was more variation in these long-term studies, but the overall pattern was clear. No difference in HbA1c, no effect on fasting blood glucose, no effect on fasting insulin, no negative effects on insulin sensitivity, and in fact,

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There were some improvements in these markers when aspartame replaced sugar. Most studies also reported either no difference or a reduction in hunger and total calorie intake. And there were no changes in leptin, GLP-1, GIP or glucagon. So I did say that aspartame itself, we don't digest it as a whole dipeptide or as a whole product and instead it's broken down into different breakdown products.

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and that if there was going to be harm from these products, we would see it. And it would be through either the phenylalanine or the methanol or the aspartic acids. Let's examine each one. Methanol. Methanol is where a lot of people focus their concerns because it is toxic at high doses. However, the danger is in the dose. Your baseline methanol exposure is roughly around

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maybe 1600 milligrams a day. Your body produces 300 to 600 milligrams. Naturally, you consume up to a thousand milligrams per day through normal diet from fruits and vegetables. And many fruits and vegetables contain significantly more methanol than aspartame sweetened beverages. uh A 355 mil can of Diet Coke contains about 18.4 milligrams of methanol. Even if you drank 10 Diet Cokes, that's 184 milligrams, that's still less than what your body produces naturally.

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And in fact, one study did test this by giving people 4,800 milligrams of Aspartame over eight hours, which is equivalent to 26 cans of Diet Coke. And the result was no abnormal increases in methanol or its breakdown product formate. The body handled it just fine. And while there are toxic effects of methanol, this requires doses a thousands of times more than you'd get from Aspartame sweetened products. What about phenylalanine and aspartic acids? These are the other two breakdown products.

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Fenylalanine is an essential amino acid found in all dietary protein. A can of Coke contains 92 milligrams of phenylalanine. A serving of chicken breast contains about 2000 milligrams, more than 20 times as much. Yes, very high doses, equivalent to over 100 diet Cokes consumed at once, can cause a small insulin increase, but it's offset by glucagon, has no effect on blood sugar. And at normal intakes of aspartame, there's no meaningful effect.

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What about aspartic acid, the other amino acid? Diet Coke contains about 74 milligrams. Serving of chicken has about 1800 milligrams, roughly 25 times more. And like phenylalanine, massive doses may cause a tiny insulin response, but at physiological levels from aspartame, there are no meaningful effects. So if you're worried about the amino acids in aspartame, you need to be equally worried about eating chicken, fish, beef.

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eggs or any protein source. And we know these foods don't cause metabolic problems attributed to aspartame, like an increased risk of insulin resistance. Of course, the one exception is that people with phenylketonuria, PKU, a rare genetic condition where you can't metabolize phenylalanine properly, do need to be concerned. And that's why there is a warning on diet Coke cans. This affects one in 10,000 people and it's picked up at birth and they're already

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following a very specialized low protein diet for life. So if the randomized control trials show aspartame do not do these negative things that are suggested, I'll just point out that the reason we keep hearing that it's harmful is because the evidence lies in epidemiological or observational studies, which are never set up to find cause and effect. Observational studies find people who consume more artificial sweeteners tend to be more obese, tend to have higher rates of type 2 diabetes, they tend to have...

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or a diet quality overall, they tend to consume more total calories. But of course the headlines will say artificial sweeteners are linked to obesity and diabetes. But what came first, chicken or the egg? And this is the problem, it's the reverse causality. People who typically use artificial sweeteners, they may be people who are trying to lose weight. They may be people who have already gained weight and are attempting to diet. They may be people who struggle with their weight.

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There may be people with metabolic issues who've been told to reduce their sugar, and there may be people who diet frequently. So when researchers find that artificial sweetener uses way more, it's likely because people who struggle with their weight are more likely to use artificial sweeteners as a weight loss tool, not because the sweeteners cause the weight gain. And this is what's called reverse causality, and it is a massive problem in nutritional epidemiology. And that's why there is such an advantage to the randomized controlled trial in this point.

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Based on this research, what we can determine is that aspartame sweetened beverages do not interfere with your metabolic health. They don't spike insulin, they don't worsen insulin sensitivity, they don't trigger the metabolic cascade that you may have heard about. They can be a useful tool if you're trying to manage your calorie intake while still enjoying sweet tasting foods. And the research shows people who use them often consume fewer calories. And if cravings are an issue,

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Aspartame sweetened beverage may actually help satisfy that sweet tooth without derailing your nutrition goals. They won't sabotage your weight loss efforts. And multiple studies in women with metabolic issues showed no negative effects on markers like HbA1c or fasting insulin. And for people who are, for example, at a normal healthy weight for them, who might love a lot of training like I do, based on this research, aspartame doesn't impair metabolic flexibility. It doesn't affect your insulin signaling.

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doesn't change how your body processes carbohydrates, doesn't interfere with fat oxidation pathways. Daily use doesn't affect glucose metabolism. Even if you were to have 15 to 20 diet drinks a day, not that I'm saying you should, um it doesn't affect glucose metabolism. And for those following any sort of periodized nutrition approach like train low strategies, using a Spartan sweetened beverages during low carb training phases won't trigger an insulin response that would interfere with intended metabolic adaptations. And

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The research shows no interference with insulin sensitivity or glucose handling, which are important for recovery and training adaptations. So they're fine for you to have in your recovery. So general takeaways then, individual variation exists. While average response shows no metabolic harm, some people may genuinely feel better avoiding artificial sweeteners for reasons that don't show up in these metabolic markers. So I do wanna acknowledge that, just trust your body and how you feel if you have this. But don't confuse,

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those effects with metabolic harm. If you're using aspartame sweetened products to replace sugar sweetened ones, that's likely a net positive. The quality of your overall diet matters. These aspartame sweetened products, they're not health foods, but they're not metabolic poison either. So just focus on the quality of your whole diet rather than obsessing over individual ingredients. And then also just don't believe that fear mongering. When you see alarming headlines about artificial sweeteners,

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Ask yourself, is this from a human randomized controlled trial or observational data? Is the dose used anywhere near what humans actually consume? Are there confounding variables? So just so you know, I'm not trying to convince you to drink diet coke, but what I am trying to do is give you some accurate information about what the research has shown versus what gets amplified on social media. So the specific metabolic concerns about aspartame, spikes insulin, increases hunger,

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causes insulin resistance and leads to weight gain simply don't hold up when we look at human randomized controlled trials. The mechanism that supposedly makes it harmful doesn't exist. And this didn't look specifically at gut microbiome effects, but remember the predicted metabolic effects that would result from microbiome disruption like insulin resistance, weight gain, increased appetite don't show up in these human studies. So while this wasn't investigated here,

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the manifestation of microbiome disruption certainly wasn't seen. So I think that's worth considering as well. So it doesn't mean that aspartame is a health food, but it does mean in the context of your otherwise awesome diet, your diet coke habit a day is probably okay. And you're not going to be sabotaging your metabolic health in the way that you might have otherwise thought. All right, team, that's it from me. And as I said, there was a much, much deeper dive on the Dr. Layne Norton podcast a couple of weeks ago.

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go check that out. I'll pop a link in the show notes to the study in question and also to that podcast. uh I have my webinar this week, Wednesday. Don't forget that. think I've got an ad for that actually in this episode as well. Any questions, comments, whatever you like, head over to Instagram thread and X @mikkiwilliden, Facebook @mikkiwillidennutrition, or head to my website, mikkiwilliden.com.

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a one on one call with me there, sign up to my webinar. Alright guys, you have a great week. See you later.