00:11
Hey everyone, it's Mikki here. You're listening to another Mini Mikkipedia on a Monday. And this week I wanted to share with you the take homes from a recent aspartame critique and review that I listened to on another podcast. And the podcast I listened to was over five hours long. So it was almost like a mini audio book, but it was super helpful and it was done in a really digestible way.

00:40
to be able to understand better the literature around aspartame. And the podcast hosts, which it was a Stronger by Science podcast, put it together because of the most recent World Health Organization sort of categorization of aspartame, which is an artificial sweetener, found in numerous foods and beverages. They had recently categorized aspartame as being probably carcinogenic.

01:09
And of course, this is going to raise a whole ton of concerns and queries around the use of Aspartame in foods and beverages. And most notably, you're going to find this in diet soft drink. So five hours was a long time, but it was incredibly insightful, as I said, and it wasn't at all boring. I listened to it over several gym sessions and runs. And I thought that the take homes would be really interesting for me to share.

01:38
because I appreciate that not everyone has the time or inclination to listen to an in-depth history related to a food chemical, despite you may well be on the spectrum of being wildly interested to extremely invested into the results of this independent review. And that's what this is. There is no investment from the podcast hosts that put together these hours and hours of research. They've got no skin in the game. They're literally just looking at independently at the research, the reports, and the media.

02:07
coverage of aspartame across time and then giving their view on it. To be honest though if you do have an opinion on the subject because I know many of people do and I certainly did, it would be worth a listen and I'm gonna put it down in the show notes where I listen to the podcast so you do so you can take the time and you know listen to my take homes from the recording you may have different ones.

02:33
given your history and what you're truly sort of looking for. And then if you've got any feedback on what I say, get in contact with me. So the first caveat to this is that I have been on both sides of the coin when it comes to artificial sweetener consumption. I wouldn't have a bar of it and warned people against it about a decade ago. Can't believe it was that long to be honest. Whereas two decades ago, didn't give them a second thought and was totally heavy handed about how I use them.

03:00
Now it'd be fair to say I'm much more moderate about it. For some people, especially people who are looking to lose weight or who have blood sugar regulation issues that require a low calorie or low carbohydrate approach, these are actually great to be able to lower calories and to that end have been found to be positively associated with fat loss. Some choose to get their calories elsewhere, like me. So I enjoy a diet soft drink. So weight loss doesn't have to be the goal for you to enjoy.

03:30
having these sweeteners. However, some people are sensitive to artificial sweeteners and don't tolerate them, so they aren't a great choice. And this is something you will not find in the research literature or any sort of World Health Organization report or anything like that. But if you know already that you are sensitive to these sweeteners, they're not a good choice for you. And then others are better not consuming foods or beverages that encourage a sweet palate, which will then trigger overeating.

04:00
There are a range of individual factors here and you'll have a good gauge on where you sit on it if you have any sort of insight into your own sort of body cues which most of you do. I do also encourage that you do have an open mind about these diet issues. That is something that I've learned and continue to learn to do over my years and it's been over 20 years as a clinician especially coming from a very fixed mindset around food. This isn't to say that you have to like them or drink them.

04:30
It's just, you know, you're losing nothing by avoiding them if that's what you choose to do. But it's really good practice not to be so judgmental of others that enjoy them. And also to be well informed about it if you are the person that likes to share your opinions around these topics. The take homes that I got from the podcast are likely because these are questions around aspartame that I've had in the past. And it was good to have these addressed in one place. If you are like me like that, again, listen to the podcast in full

05:00
So aspartame, it's a dipeptide, a chemical compound made up of two amino acids and a methyl group. The amino acids are phenylalanine and aspartate. Phenylalanine is abundant in the diet of people who eat protein-based foods. People consume around 3-3.5 grams if you have around 80 grams of protein a day, which is a pretty low protein intake actually. You might consume around 8 grams a day if you have a higher protein intake.

05:29
Aspartate is around the same. Methanol is generated from the methyl group when aspartame is consumed and is structurally similar to ethanol, alcohol, but is much more toxic. However, if you consume fruit and vegetables and digest and ferment fiber also, this equates to around one gram of methanol that you're consuming in your diet each day, especially if you consume alcohol also.

05:57
If you consumed the maximum amount of aspartame that the current guidelines allow for when consuming aspartame, that's around 40 mg per kg of body weight, you would end up having 1.16 grams of phenylalanine, 1.36 grams of aspartate and 130 mg of methanol, amounts far lower than what we typically have in our diet. Now remember I said

06:26
People who eat 80 grams of protein, a pretty low protein intake, have around three to 3.5 grams, whereas the upper daily limit of Aspartame, the artificial sweetener, suggests that you can have an upper limit of 1.16 grams. Now, bear in mind that this is the amount that you might have in nine to 14 cans of Diet Coke each day if you weighed around 70 kilos.

06:52
People generally consume around 4 mg per kg body weight a day, around 1 tenth of the allowable limit. So this is always really good to have in context because when you see an upper limit of a certain amount it's hard to quantify how much this is. This is only in reference to aspartame and I did want to mention the naturally occurring amounts that you find in fruits and vegetables and protein foods because you are getting well above what that acceptable daily allowance is.

07:21
just naturally through a good whole food diet. Anyway, another reason why people sort of freak out I think about aspartame is because they see the warning on diet soft drinks that says contains phenylalanine and get a little bit freaked out from it because it is a warning. However, this is for the one in fifteen thousand people, one in fifteen thousand, who have a condition called phenylketonuria.

07:49
which would be determined at birth. Very soon, as soon as a baby is born, there is a test that they do to determine whether or not the baby has phenylketonuria. However, it does give the impression that phenylalanine itself should be avoided, which makes sense, right? Because if you see a warning sign, even if you don't understand the little bit that says it's for phenylketonuria, which is a name for people who have phenylketonuria.

08:19
you look at that warning sign and go, this must be bad. But it is only a bad choice in this context for people with that actual medical condition. And just so you know, phenylketonuria or PKU is caused by a change in the phenylalanine hydroxylase gene. And this gene helps create an enzyme needed to break down phenylalanine. And it's a rare genetic condition present from birth where the body is unable to break that down.

08:46
If you are unable to break it down, then this can lead to brain damage, intellectual disabilities, behavioural symptoms or seizures. So the treatment is a strict diet with limited protein for these reasons and as I said, this is why they test for it at birth. Another reason why people freak out about diet sweeteners is because the earlier studies on sweeteners done on saccharin, not aspartame, they're different, found that rats developed bladder cancer from the intake of that substance.

09:16
This then led to warnings being placed on food labels in the 1980s that contained saccharin. However, interestingly, the mechanism with which saccharin led to bladder cancer is not a physiological pathway in humans, so therefore it isn't a risk. So the bladder cancer, it's due to the way that the saccharin is metabolized and it forms toxic microscopic crystals in the bladders of rats.

09:46
have this pathway in our body to be able to do this. So it's not relevant to human carcinogenesis. Despite that though, the warnings were placed on the labels and the amounts used in the trials for saccharin just FYI, were well above the acceptable daily limit of that sweetener. Another study that they talked about in the podcast, and like I said, this is just my little cliff notes, my take homes, was called the Nutrisante study.

10:15
and it found that 3.24 mg of aspartame was associated with an increase in cancer of 12%. However, if this was actually the case, then the podcast hosts talking about the topic said that this would mean it would be one of the most toxic substances on the planet. Because 3.24 mg is so low compared to what we naturally find in the diet. Remember I said people who consume protein have about 3-3.5 grams.

10:45
And this is 3.24 milligrams. So it's like 1,000th of what you would otherwise find. And then looking further, this risk, though in the Nutrisante study, even though they found this association, increased risk by 12%, when looking further, the risk didn't increase as the amount of aspartame consumes go up, i.e. there is no dose-response relationship found. Now there is a fundamental pillar in science of what is required

11:15
as to whether we can confidently say something is a proven causal factor. And that is the Bradford Hill criteria. And the Bradford Hill criteria says that a dose response relationship for any association needs to be present in order for something to be a proven causal factor. So whilst there was this very mild association found, when the dose of aspartame went up, the risk did not go up. So...

11:42
you know, this may be spurious, it may be nothing at all. And that's certainly what would be suggested if you test the findings of the study against the Bradford Hill criteria. Another take home I got from the study was that the whole World Health Organization sort of report came from the International Agency for Research on Cancer classification, which is the one that deemed that aspartame was a probable carcinogenic.

12:10
The IARC classification uses hazards ratios to determine a hazard. And it's the idea that something can do something bad. A risk is the potential outcome of a hazard, given appropriate circumstances and level of exposure. A good way to think about this is that a hazard ratio is like the mere existence of traffic presents a potential hazard. Your risk of getting run over in traffic though, depends on several things.

12:40
How you behave in traffic. Do you run out in front of cars that are moving? Do you look both ways before stepping out onto a road? What is the weather like? Do you use traffic lights? You know, a truck will kill you if it runs you over and it's going fast enough. That's a hazard. Your risk of this happening though, is determined on all of these other variables. Are you near the truck? Are you looking both ways for the truck? All of those things. And it cannot be determined by the existence of the hazard itself.

13:08
The IARC assesses hazards and not risk and cannot give details of circumstances and magnitude of that risk. So it doesn't consider the mode of exposure or ingestion either. So even just the mere sort of knowing that should really tell you a little bit of something about risk because risk is the thing that we're interested in. Just the mere sort of determination of hazard is not enough to give us insight into this.

13:36
A second point on the classification is actually the categorizing of aspartame into 2B, which is the category that it was in, possibly carcinogenic. This is a third of four categories. There used to be five categories, but the last group, that it doesn't cause cancer, was scrapped, as after 20 years there was only one agent that was classified. That might tell you a little something about the things that are either tested or how things are categorized. Just to go through that though.

14:06
Group 1 requires strong evidence in humans that something causes cancer. Think asbestos. All this strong evidence in animals and there is mechanistic plausibility that the agent could cause cancer. Epstein-Barr virus, UV rays from the sun, silica, diesel exhaust, processed meat, wood dust, these are all examples of things that fall into group 1. So there's strong evidence in animals and there is mechanistic plausibility.

14:36
plausibility that their agent causes cancer in humans. There have been no randomized control trials here. Group 2a is something is probably carcinogenic. There is strong evidence in animals, but there is weaker evidence in humans, limited epidemiological evidence. Think anabolic steroids, nitrates and nitrites, high temperature frying, red meatballs here, a hot mate, which is a traditional South American beverage, night shift work.

15:04
and just hot beverages in general, which interestingly are above 65 degrees. Group 2b is something that studies have found limited carcinogenicity in humans and less insufficient in animal trials, or inadequate evidence in humans, yet sufficient evidence in animals. But it's unclear that it is possible for mechanistic plausibility. Therefore, it will go into group 2b. Or

15:29
If there is limited evidence across human and animal studies but strong mechanistic data in a petri dish for example, then it can also go into 2b. This is where aspartame is. It is in there with ginkgo biloba, cell phones, saffron from spices and sarsaparilla which is something I haven't heard of in a while but man I remember it being delicious, aloe vera, fermented vegetables are also in this group.

15:57
So you've got group one, strong evidence in humans or strong evidence in animals and mechanistic plausibility. You've got group two A, strong evidence in animals but weaker evidence in humans, limited epidemiological evidence. And group two B, limited carcinogenic in humans and less than sufficient in animal trials or inadequate evidence in humans yet sufficient evidence in animals. But...

16:25
unclear that it is possible from a mechanistic plausibility perspective. Isn't that interesting? So something can be categorized as probably or possibly carcinogenic, yet there's very little evidence to even suggest that that's the case. And this is again based on hazard ratios, so not a relative risk, so just is there a hazard? And it's from the International Agency of Research on Cancer. So hopefully you...

16:52
You can see that despite the classification that aspartame has earned, there is no context here with regards to risk. This classification is just about hazard, but press releases and the general population can easily misinterpret this meaning and thus misrepresent the data. Also the other thing to note, it's not that the IRRC are doing this and trying to do a number on us, but essentially they're not a group that makes recommendations on intake.

17:19
They are set up to direct future research, so it is more for scientists to therefore do it. And that is something else that is another point that is missed by the sort of social media representation on the topic. The IARC have rated aspartame as insufficient evidence for all cancer types, however, based their human evidence on hepatic cellular carcinoma cancer.

17:46
HCC. It's a type of liver cancer. Very rare, very nasty. Three cohort studies, which this is epidemiological research. However, chance, bias, and confounding couldn't be ruled out in these three highly controlled and well-designed studies for all cancers, including the HCC subtype. So as I said, HCC is a serious cancer. It has a five year survival rate of below 20%.

18:14
However, it's very rare with a 0.04% prevalence rate in the studies that were reported. There was a 6% increased risk, making this 0.04% risk to 0.042% risk. If you consumed 10 diet soft drinks each day, this risk increases to 0.06%. There were some confounding issues. It was self-reported data, as is the nature of epidemiological research.

18:43
There were mutual associations with metabolic syndrome, non-alcoholic fatty liver disease, obesity, and type 2 diabetes. It's worth noting this. One of the studies only found this association in people with type 2 diabetes in the first place. One of the papers also was no longer significant when BMI was adjusted for. There may also be residual confounding from factors that haven't been accounted for, such as physical activity, amount of sleep someone has, sedentary behavior.

19:12
we can't account for everything and they didn't measure these things. And then what does cause cancer mechanistically? If we think about the big picture, cancer falls under the following umbrellas. Things that directly damage DNA that cause little areas in your proteins that can predispose you to developing cancer. Things that directly affect the expression of genes that either cause or suppress cancer cell growth. Things that affect cell turnover proliferation.

19:39
is every time DNA replicates, there is a risk, there is a small transcription errors in the DNA, and that the more they replicate, the more likelihood of damage over time. And within these three sort of major subgroups of how we develop cancer, there's no good evidence for aspartame to act mechanistically in any of these ways. High doses in animal models can increase inflammatory pathways that are biomarkers of cancer growth, and that is basically the extent of it.

20:09
So those were my major take homes from the Stronger by Science podcast. If anyone else did listen to it, obviously, like they spent five hours. I really gave you just some broad overview. There were so many other things that I could talk about. They go into depth of sort of media analysis. It was awesome. They did a massive sort of dive into those studies like the Nutrisante study. And they also talked about saccharin as well as a sweetener. Like they did a huge sort of deep dive into that.

20:38
sort of to kick things off. But ultimately, the IARC report that called it possibly carcinogenic was never designed to be recommendations for intake. It really is a recommendation to scientists to do future research on these findings. And you can see just how weak the evidence actually is for anything in that group. Super interesting, particularly because we know that fermented vegetables

21:07
also in the same group, are always recommended with regards to gut health and our gut microbiome, yet these also fall under that sort of 2B category. So hopefully this gives you a little bit of perspective and context sort of based on what I got from the podcast. I will link to the podcast in the show notes, so you can go and listen to it, and then you can give me your feedback if you like as to what you found really interesting. And look, like I said, you don't have to like aspartame. You don't have to love.

21:36
diet soft drinks. They're still rubbish right? Like it's not like they're a health food but they're probably not gonna kill you and I think there's a lot of guilt attached and associated to different foods and beverages and there's virtue signaling that goes on when you avoid them and I think we just need to drop the judgment of people who consume this stuff and let people do what people do. If they don't agree with you you do not have to drink them and you do not have to like them. Anyway so I hope you enjoyed

22:04
listening to my take homes. You can catch me over on threads, Instagram and Twitter @mikkiwilliden, Facebook @MikkiwillidenNutrition, head to my website mikkiwilliden.com. Alright team, you have a great week.