00:05
Hey everyone, it's Mikki here. You're listening to Mini Mikkipedia on a Monday. And today I want to chat about whether or not sucralose, which is a widely used artificial sweetener, whether it hijacks the brain. And by that I mean, does it impact our appetite and our satiety hormones to the point where our body cannot recognize its hunger or satiety cues and can lead to subsequent

00:35
overeating. So what I will say is that the science in this area is not settled and will never be settled. And in fact, I did a mini Wikipedia episode on a spa team maybe a year ago now, and it sort of just impact on health perspective. But the question as to whether these products are harmful or helpful is a super interesting one. And this has been studied, sucralose particularly has been studied

01:02
a number of times with regards to questions around appetite signaling. And what prompted me to do this little quick mini episode for you is that I just had an email pop into my inbox from someone I follow who's very smart and she's very mechanistic and gets into the weeds. And it highlighted the idea that in fact, yes, sucralose does hijack the brain. And so I just want to go through the, and I will link the

01:29
article with which this was referring to. I want to go through the mechanisms and what the study found, but also what the totality of the evidence says to date, because one study will neither make or break a particular area of interest. So this study was published in Nature, which is a really great journal, and the study itself was non-caloric sweetener effects on brain appetite regulation in individuals across varying body weights. And I think that is important because

01:57
We know just looking at research that body weight or body fatness can impact on appetite signaling. In this study, sucralose consumption leads to a 7.9 % increase in blood flow to the hypothalamus, and that's an area of the brain which is central to appetite control. This is compared to both sugar and water. This rise in the hypothalamic activity is a neural marker that is typically associated with increased hunger.

02:27
which matched participants' reported hunger ratings. The researchers also observed stronger connections between the hypothalamus and brain areas involved in reward and sensory processing, suggesting that sucralose may enhance food-seeking behavior. In contrast, when these participants consumed sugar-sweetened drinks, such as, you know, whatever it was, juice or soda, they experienced a higher glucose, insulin, and GLP-1 levels,

02:56
which were hormone signals that promoted satiety. These changes were associated with reduced hypothalamic activity and decreased hunger, aligning with the body's natural response to energy intake. And this study also found that these results were especially pronounced in women and people categorized with obesity and with those with lower insulin sensitivity who appeared more sensitive to sucralose effect in the brain.

03:23
This study was 75 adults aged 18 to 35, and it was an acute study. So it happened across three time periods or three sessions where they had a sugar sweetened drink with 75 grams of sugar, a sucralose sweetened drink, which had the same perceived sweetness as the sugar, or they just had water. And they used MRI imagery to look at the brain activity. And they also measured glucose, insulin, and GLP-1.

03:53
So while sucrose led to these 21 predictable metabolic changes with increases in the glucose insulin GLP-1, sucralose had no such effect. And that makes sense, right? Because sucralose is an artificial sweetener. It is several hundreds to thousands times sweetener than sugar. And so in essence, it's calorie free. Now, what was interesting here was that sucralose triggered an increased hypothalamic activity, especially in our hunger center.

04:22
of the hypothalamus, but the response varied by body weight. Individuals that fell within the normal BMI showed sucralose-induced activation in areas typically associated with fullness. Individuals with obesity showed activation in the hunger-related areas, suggesting a heightened drive to eat. Hunger ratings were higher after sucralose than sucrose, but were not significantly different from water. So this points to a key finding.

04:51
The authors suggest that calorie containing sugar suppressed appetite, a response that isn't seen with sucralose. Sucralose also was found to strengthen communication between the hypothalamus and the brain areas involved in reward, motivation, and sensory processing, including the ventral striatum and the prefrontal cortex. Sugar did not enhance these connections to the same extent. Therefore, the authors posit that this explains why the sweet taste without calories could increase the desire for food.

05:20
because the brain receives a sensory signal that interprets it as energy intake, but when the expected metabolic feedback doesn't follow, it stays on alert, increasing motivation to seek more food. So the body is primed for food, doesn't get it, it wants more, so that increases our drive. So while sucralose is calorie free, what the authors of this study suggest is that it isn't metabolically inert, at least not in the brain. So it may activate hunger-related

05:48
pathways and reward circuits in a way that sugar doesn't. Now these are acute effects and long-term implications do remain uncertain, but the author suggests this challenges the assumption that non-caloric sweeteners are neutral substitutes for sugar. In short, sweetness without the calories can confuse the brain. Sucralose may be able to trick taste receptors, but without the metabolic response that normally follows. The brain may ramp up hunger and reward signals instead of turning them down.

06:17
This was sort of the premise, I suppose, of the email that came in this morning. And it did prompt me to just have a bit of a dive because one study should not be the basis of your conclusion on an area or your thoughts on an area. Because sucralose, as I've said, has been studied extensively across the course of its history, if you like, as have a lot of the artificial sweeteners because of their

06:44
I'm going to say chemical nature and I just mean that their inclusion in foods that would otherwise be sweet. And this question as to whether or not sweetness hijacked the brain has been studied a number of times. While there are some limitations to the study, what I will totally acknowledge is that, you know, there is this idea that a sweet taste without accompanying energy may in fact confuse the body's regulatory system. So this study was just sort of confirming

07:13
other studies that have shown this because of the mechanisms I've suggested that the body expects energy. It's not coming in our appetite hormones or post ingestive metabolic signals. Insulin gel P1 doesn't follow and this may blunt our body's predictive responses over time. It did use the MRI.

07:36
which is a really great way to determine sort of what's going on in the brain. So that was super interesting. And we do know that changes to appetite response can differ by BMI status with people with obesity showing greater reward related activity. So they may be susceptible to food cues and dysregulated appetite control. However, some important caveats and what we still don't know.

08:04
This is an acute study versus chronic. So this study shows acute brain and hunger effects, but those long-term implications do remain uncertain. And we do know that there are randomized controlled trials and meta-analyses do show neutral or even modestly beneficial effects on non-nutritive sweeteners, which sucralose is on weight when you use to replace sugar, especially when part of energy reduced diets. So.

08:31
If sucralose was really causing a huge issue with food intake and energy intake, you wouldn't expect to see a favorable impact on weight. Yet, of the meta-analyses do show this. The concern that non-nutritive sweeteners may increase appetite and food intake later on does seem to be context dependent and isn't consistently seen across all trials. To my point, you do not see people gaining weight when they use sucralose instead of sugar.

09:00
So we do not really know yet the real world effects when we're looking at sucralose in the context of broader dietary patterns, i.e. a pattern that is sort of set up for a calorie deficit in a nutrient-dense diet that has all of the features of good dietary practice, as I talk about a lot on this podcast and everywhere, basically. So I don't think that we can determine that sucralose is categorically

09:30
most randomized controlled trials which last sort of weeks to months show that non-nutritive sweeteners do not increase energy intake and often reduce total calorie consumption as I mentioned. So when we look at nutritive sweeteners as a straight swap for sugar, you do see a reduction in body weight because those calories aren't replaced. Potentially if you're layering on non-nutritive sweeteners to a calorie dense diet,

10:00
potentially that could drive an appetite response. And I remember seeing actually someone talk about this, that when you have a sweetener in the context of, let's just say like a diet Coke or a low fat food, like sucralose is often used in yogurt. If you have the sweetener in context of low fat, it actually is better for the appetite and doesn't drive the same appetite signaling.

10:26
as it does if it's combined with fat. So that's an important thing to sort of consider, albeit the study found that the sweetener alone caused those changes in appetite responses. But I just thought it was worth noting that potentially the context of the food it's in could change the appetite response. So while we need to think about context and we need to think about overall dietary patterns and what else is going on, it is interesting that if I do look at

10:54
other research that looks beyond brain imaging studies. There was an article published last year that looked at sucralose on metabolism and its role in shaping obesity trends. That's the article name and I will pop that also in the show notes. And interesting, extended beyond, as I said, the brain imaging and looked at other ways with which sucralose could

11:23
potentially impact on metabolism and overall body fatness. So it reinforced a lot of the findings of that brain imaging study, but it also broadened the context. it suggested that sucralose, this particular review, sucralose could alter gene expression in hypothalamic neurons, like our sweet taste receptor, T1R2, which could influence long-term appetite signaling.

11:53
So might impact more than just short-term hunger markers. Some studies have shown that sucralose reduces beneficial gut bacteria, such as bifidobacteria, lactobacilli, and increases pro-inflammatory species. And this gut dysbiosis has been linked to metabolic syndrome, increased adiposity, insulin resistance, and inflammation, and even depression-like behavior in animal models.

12:22
So this is an important extension because microbiota disruption can indirectly influence brain hunger signaling via the gut brain axis, reinforcing that brain imaging studies findings, but just from another angle. And there was a study that was a double blind randomized controlled trial that showed chronic sucralose consumption for 10 weeks, which is a pretty long period of time, increases insulin levels and reduces insulin sensitivity, even in healthy young

12:51
adults, which suggests not only acute disruption and hunger signaling, but potential long-term impairment in glucose metabolism. And that is something that you can't really see in that brain imaging study because it was an acute study. So this review article sort of contributes to some of that body of knowledge that sucralose may have negative impacts on appetite signaling, but it could be dose and context dependent.

13:18
particularly in individuals already with obesity or insulin resistance, women as the brain imaging studies showed, and people with disrupted microbiota. And it really does just call for long-term human studies and refinement potentially of acceptable daily intake levels is what they've suggested. But again, if I look at this review article, then I just look at the context with which sucralose is actually consumed in. Often it is consumed in people

13:47
who are with obesity, who may have insulin resistance, and in the context of a calorie controlled diet, there are no obvious harmful effects. So it's a super interesting area and I'm not, I've been very much down the rabbit hole of extremely avoiding artificial sweeteners, but I've also been absolutely the opposite and going gung ho on them like back in my early years. And now I'd say I'm somewhat more moderate on

14:16
what I think about these artificial sweeteners. And sucralose being one of the most available one that you find in protein powders and yogurts, just, you know, everywhere. So in conclusion then, what I think we've got are several mechanisms to show that in certain populations, there may be an alteration in brain appetite signaling and also the gut microbiota. To what extent this impacts long-term on health is yet to be determined.

14:46
And I think in practice, I know that there are some people who find that they can't switch their hunger off with artificial sweeteners, that they don't actually help them. And in fact, they make them crave more food. So for those people, and not just artificial sweeteners, I've seen this with stevia and monk fruit and stuff as well, then you're better off sort of eliminating them or moderating them in your diet.

15:10
And for others, I think they can be a really valuable tool, but I do think it's all about dietary context. if I'm honest, I'm not a huge fan of being like I used to be back in the, you know, sort of early 2000s when I would have everything was artificially sweetened. You know, now I'm, as I said, more moderate, but I think you've got to think about it in the context of your own diet and how you use them and just notice how they may affect you.

15:38
think that that sweet taste plus the fat together, I do think there's something there. And if I can find the reference to what I'm talking about, I will include it in the show notes. But I've included the link to the article I'm referring to, that randomized controlled trial with the young adults with the elevation in insulin, and that larger sort of review article looking more mechanistically at both gut and brain, which I think you'll find interesting if you're interested in this sort of thing. Anyway, so.

16:07
You did another thing to ponder really on artificial sweeteners and health. Leave that there. Ask me any questions if you've got them. I'm over on Instagram threads and X @mikkiwilliden, Facebook @mikkiwillidenNutrition. Head to my website, mikkiwilliden.com. hey, this week I'm coming out with Monday's Matter Accelerated. This is only on sale for five days. If you've wanted to.

16:33
dip your toe into Monday's matter, but haven't wanted to commit to the full thing. I 100 % recommend this. Great little reset. Lots of learning goes on in that 28 days. Not an overwhelming shopping list to buy. Not a meal plan. It's not even a meal plan. Jump on my website, check it out. I'll be sending you an email anyway, if you're on my list. All right, team, you have the best week. See you later.