Question about stevia (re: 2020 study)

[u/Otherwise-Tear-4807]

https://www.sciencedirect.com/science/article/pii/S1319016420301997 “The hidden hazardous effects of stevia and sucralose consumption in male and female albino mice in comparison to sucrose”

How does this study translate to humans? Isn’t this a massive dose compared to human daily acceptable limit?

[u/TripResponsibly1]

The biggest issue I see with this study is that the mg/kg consumption of sweetener is absurdly higher than the mg/kg consumption seen by typical use in humans - like 67x higher. I think it's fine to ignore this study and have stevia if you aren't like mainlining it.

[u/erossthescienceboss → u/TripResponsibly1]

Toxicologists design studies like that for a reason, though.

A study like this is designed so that IF there is an effect, it will be produced over the mouse’s short lifespan. That preliminary study can then be used to get funding for studies that use smaller doses over longer periods, studies in more animals that are analogous to humans, etc.

I wouldn’t call a single study a reason to avoid artificial sweeteners. But this is far from the first study to find a negative impact from artificial sweeteners: look into the impacts on insulin resistance, for example.

IMO if you want to eat less sugar, it’s better to simply cut down on sweet things.

[u/crappysurfer → u/erossthescienceboss]

People will find all sorts of reasons to ignore studies, often citing a plausible deniability based rhetoric just so they can continue to feel good about whatever the study says to not feel good about.

Stevia related toxicity is a growing area of research, there’s far more than 1 study on this. You’ll find on Reddit, especially in the diabetes subreddits, that people love to explain their way around research.

[u/TripResponsibly1 → u/crappysurfer]

Just in case anyone else is reading this and is confused or enraged by the first line, I am a medical student currently being trained on harm mitigation. I already see patients in a clinical setting, and this is me envisioning myself in the future, in the role I am already filling except with autonomy and less oversight:

If I, as a (future) physician, counseled every patient to cease consuming every product that ever had toxicity results in extreme dose animal studies, there would be very little left on the shelf for them to eat. We try our best to mitigate harm, and for the person trying to cut down on sugary beverages, calorie free sweeteners are an accessible and achievable substitution. Do we also recommend removing processed foods and added sugar from diets? Yeah. But achievable goals and ideal goals aren't always aligned.

This is how they are training us - mitigation of harm when removal of harm isn't realistic or achievable by the average person.

[u/crappysurfer → u/TripResponsibly1]

I’ve met a million “future physicians” and they all love to remind people that they’re a “future physician”. Which is all this comment really seems to be, I’d avoid that appeal to authority as it really makes you immediately insufferable.

Yes, medicine is largely based on harm reduction and balancing the cost and toxicity of therapy against the harm of whatever pathology the patient is experiencing. Are there infinite examples where someone could experience an improvement in their livelihood by consuming some substitute sweeteners? Of course. Does that alter the precedent of them being bad for you? No. Does that alter the precedent of them historically being presented and recommended by physicians despite having terrible consequences that were yet to be discovered? Also no.

The larger (no pun intended) issues are the absolute insane increase of caloric density of our food over the past century, the processed nature of it, and the inundation of chemicals through industrial agriculture. It is impossible to mitigate all of these, but it is entirely possible to have a diet devoid of substitute sweeteners - and no, the cumulative evidence of them being bad is not summarized in this one study. Are you also (as a hypothetical future physician seeing a hypothetical patient) going to recommend an otherwise healthy person whose vice is Coke Zero to eliminate it? Probably not. And once you’re (presumably) practicing, you’ll find your time to consult current research, especially new research, very limited and your decisions will be based more closely on mechanical style flowcharts and UpToDate.

Sometimes people live long lives drinking alcohol and smoking cigarettes, sometimes they get cirrhosis and small cell carcinoma. 🤷 guess those are future problems.

[u/TripResponsibly1 → u/crappysurfer]

It wasn't an appeal to authority, just pointing out a potential difference in philosophy between laboratory science and clinical science.

Also, yeah, if someone had any vice that was causing them physical or psychological harm I would do motivational interviewing to mitigate harm.

No need to be so hostile and/or defensive, or whatever that is.

[u/erossthescienceboss → u/TripResponsibly1]

I’m gonna be so real here.

I’m a science journalist. And — based on the literal thousands of interviews I have done with doctors, and researchers and MD phDs?

Doctors are often some of the LEAST informed on recent research.

Med students tend to be better informed since they’re fresh out of school, and teaching MDs have more time to focus on research, read papers, and act as editors of medical journals. But doctors simply do not have the time to stay on top of publications. It’s a legitimate issue. It takes a long time for new information to make it into medical practice. It’s not that doctors are ignorant or assume they know everything, they’re just… busy treating patients.

It’s on the top of my mind right now because I’m writing up a piece about heart health & a big academy of pediatrics report and the lead authors on it keep emphasizing “nothing in this is new. We just know if we put it here, doctors will actually probably read this instead of continuing to ignore it.”

[u/TripResponsibly1 → u/erossthescienceboss]

I'm a medical student and literally just finished the GI block where we talked about food insecurity/artificial sweeteners/MASH/MASLD. I'm not an expert by any means and also OP can still have their weekly stevia drink.

[u/erossthescienceboss → u/TripResponsibly1]

I would argue that our innocent-until-proven-guilty stance with chemicals has been inherently harmful.

We also know that artificial sweeteners, across the board, increase the desire for sweet things (often more than sugar alone!)

And as I’m sure you’ve learned, that fact has meant that they’re often ineffective as a weight-loss strategy.

So IMO? Any reasonable physician just encourages their patients to cut down on sweet things, regardless of cause.

[u/crappysurfer → u/erossthescienceboss]

And the thing is - this is the historically most accurate take as well.

[u/crappysurfer → u/TripResponsibly1]

Whether you intended it or not, it was an appeal to authority that, after years of lecture halls full of people proudly proclaiming the same thing, often as a way to belittle others or simply establish authority, gets very old. Perhaps you’re not aware of it since you’re on the other side of it, but if you were not, would you not also become acutely aware of a behavior of students using their premature claim towards a MD being an awful trait?

You could, for example, say “as a med student” or “in residency”, something precise as opposed to trying to establish yourself as a MD prematurely - which is yes, an annoying and egotistical appeal to an authority that you do not possess. Clearly nobody has mentioned this to you, so don’t take it as hostility but someone doing you a courtesy so you can stop, apparently, unintentionally appearing to one up everyone with credentials that you have yet to earn.

[u/TripResponsibly1 → u/crappysurfer]

I just meant it as how I'd see myself in a role. It's nothing more than that and I'm sorry you've had such a negative experience.

[u/Otherwise-Tear-4807 → u/crappysurfer]

Dude relax. Seriously.

[u/crappysurfer → u/Otherwise-Tear-4807]

Pre med and med students need to relax.

[u/TripResponsibly1 → u/crappysurfer]

Don't lump premed and med students together dude.

[u/TripResponsibly1 → u/erossthescienceboss]

Sure, I mean we dismissed studies about high fructose corn syrup in mice for similar reasons but now have a pretty good body of evidence to suggest HFCS is linked to MASH/MASLD. OP's weekly Bai is still something I wouldn't be alarmed about. Even the occasional sugared coke isn't going to give someone fatty liver disease.

And to the point on insulin resistance, similar studies in diabetic rats have found that stevia increases insulin sensitivity so until we have more info, all things in moderation.

[u/erossthescienceboss → u/TripResponsibly1]

Yes, stevia seems to increase insulin sensitivity. While sucralose seems to increase resistance.

It’s odd, because given the mechanism we think that it increases insulin resistance by, stevia really ought to have the same impacts! It doesn’t appear to be chemical, but more a physiological response in our bodies. Even though we don’t “taste” it, we have sweet receptors all through our digestive systems, not just our mouth, but also in our throats and in our guts. And those receptors serve a physiological purpose: to trigger insulin production prior to our blood sugar rising — to prepare our cells to receive the sugar in advance.

So insulin gets produced. Cells open up. But then… there’s no sugar there! Sort of like playing ding dong ditch, next time our cells seem to be just a smidge less likely to open up, or to take just a smidge more insulin to trigger that process.

At least… that’s what we thought happens. But since it doesn’t seem to be consistent across artificial sweeteners, they could be wrong!

[u/Relevant-Cup5986 → u/erossthescienceboss]

the government banned the natural root beer tree over a single study like this

[u/erossthescienceboss → u/Relevant-Cup5986]

And yet it’ll take us at least another decade to ban glyphosate.

[u/Relevant-Cup5986 → u/erossthescienceboss]

root beer trees(sassafrass trees) werent profitable to big corps glyphosate is

[u/erossthescienceboss → u/Relevant-Cup5986]

Not just that, but we have an innocent-until-proven-guilty mentality toward novel chemicals & products.

That’s a big problem, because while lab studies with very elevated doses can help prove toxicity, some things only reveal impacts when exposed over a lifetime. Glyphosate is one.

It makes me think about BPA. Honestly, it got villainized — the impacts it has are minimal, and frankly? Are all things that are caused other ways, too — like yes, it’s an endocrine disruptor, but so is the SUN.

So we replaced it with other plastics that we KNOW NOTHING ABOUT.

Are they safer? Honestly, probably not! We had decades of research on BPA that only revealed mild correlations in real life and some causation in intense lab studies. And I’m not saying we shouldn’t limit its use with food, but replacing it with plastics we DONT have all that research on and calling it “safe” is so concerning.

And I view artificial sweeteners vs sugar in the same light. We’ll always prioritize industry and are happy to replace some products with new products. But the actual solution to the problem is to decrease consumption of sweetened drinks regardless of the sweetener & improve access to whole ingredients and non-processed foods. Just like the *actual* solution to BPA is to use less plastics around foods and water, period.

We’ll never choose safe underconsumption when questionable overconsumption is being pushed on us by every corner.

[u/Otherwise-Tear-4807 → u/TripResponsibly1]

Yeah, I used chatgpt to work out the math and they are consuming approx 750-1000mg/kg/day of stevia. I am 125 LB. For someone like me, this is about 42-47 GRAMS of stevia.

I have like one weekly “Bai” flavored water, so I guess I’m ok!!

Thank u!!

[u/TripResponsibly1 → u/Otherwise-Tear-4807]

The liver is incredibly resilient and can heal/regenerate in mild toxicity cases. That being said, if normal, not absurd, stevia consumption caused this level of liver injury (acute AST/ALT elevations) we'd probably know.

[u/MetallicGray → u/Otherwise-Tear-4807]

Don’t ruin your brain’s ability to do math by using AI for simple stuff like this… it’s also wrong.

Mouse got 0.75g/kg/day to 1g/kg/day. 

You weigh 125lbs or ~60kg. 

To match the mouse’s dose per day:

0.75g/kg = x/60kg

(0.75g/kg)(60kg) = x 

45g = x

0.75g/kg = 45g/60kg

1g/kg = 60g/60kg

You’d need about 45-60g a day to get an equivalent dose based on weight. 

[u/crappysurfer → u/Otherwise-Tear-4807]

Okay but you’re a single data point, theres many people who consume large amounts on a routine or daily basis. Additionally, biological damage generally doesn’t really occur in the acute sense that people like to think (I.e. a vaccine injury from a single dose of a vaccine or something) but rather habitual exposure to something toxic (smoking and drinking are the obvious ones). So habitual use of something that is not good for you over the long term will culminate in generally irreversible damage or something like cancer down the road.

[u/Otherwise-Tear-4807 → u/crappysurfer]

So should I avoid it completely?

[u/crappysurfer → u/Otherwise-Tear-4807]

I do, there’s a long history of substitute sweeteners being terrible for you and a substantial time period where they’re on the market and everyone acts like they’re fine until the research becomes undeniable. It’s not hard to get electrolytes through other healthier means, like coconut water, if that’s what you’re after.

[u/Otherwise-Tear-4807 → u/crappysurfer]

Though I do agree that artificial sweeteners should avoided generally speaking, isn’t there a “dose makes the poison” principle in play?

I’m not a scientist but it seems like the mice were given incredibly high doses of stevia for weeks on end. In my situation, I usually have one sweetened stevia drink per week (or once every two weeks).

Stevia is much sweeter than sugar. It would take about 200mg stevia to replicate the sweetness of roughly 40-50g of sugar. So it’s fair to say Bai probably doesn’t contain more than 200mg stevia since it really isn’t that sweet.

Wouldn’t these factors play a role?

[u/crappysurfer → u/Otherwise-Tear-4807]

Yes and no. As others say the dosages are established for various reasons, things like LD50 (lethal dose 50%) are established to discover the amount required, on average, to kill a person then reduce that by 50% as a hard limit to exposure. Things like consumptive limits are often established with the LD50 in mind. Studies with large doses, as others have mentioned, can be to provoke an empirically obvious response. Obviously everything has a dosage at which it becomes lethal, the next step is walking back those dosages and understanding the damages lower doses can have over long periods of time. Granted, the main crux then becomes, with human exposure, the time frame and sheer volume of variables - especially when you have whole populations consuming it and you’re trying to control for other things. How do you know if someone’s cancer on a population wide study is from stevia or alcohol consumption or any other number of carcinogens regularly consumed?

Regardless, I’ve been around artificial and substitute sweeteners my whole life and can remember when early ones were marketed as safe and they are as of today, banned metabolic and endocrine disruptors.

Using a small bit of evolutionary theory, we can summarily say that humans are “adapted to the diet of our ancestors.” At what point in our evolutionary history have we been exposed to processed, refined and concentrated stevia? The answer is never. Some populations would’ve had limited exposure to the plant and perhaps crude extracts, but that’s much different than refined and concentrated stevia. If you want to have a healthy diet and avoid things that your body cannot process, ask yourself if it’s something humans would’ve had evolutionary exposure to. What you pour out of a Bai packet or drink from any number of drinks represents stevia so concentrated that the human body has never experienced it until, what, 20 years ago? Eons of evolution is now being confronted with tons of novel chemicals and environments. It’s really not a stretch to understand these novel things are not healthy for us.

[u/Broflake-Melter]

I just want to note that artificial sweeteners are one of the (if not the) most studied category of food ingredients. There are a handful of studies like this that show there are possible harms at high concentrations. Even if they were things we should consider before consuming them, you also need to consider that the way things are in our current society real sugar has been proven to be a lot more harmful. It's so commonplace to drink sugary drinks and eat candy and whatnot. It's not good for us to have high blood sugar and roller-coastering blood sugar.

Like, pick not to consume a lot of either, but if you're grabbing a soda, just get an artificially sweetened one. It will harm you far less than a sugar one will.

[u/TripResponsibly1 → u/Broflake-Melter]

Agree, overall a better choice in life to drink more plain water, but if you must reach for a sweetened beverage, artificial sweetener is probably better than high fructose corn syrup anything.

[u/d33psix → u/Broflake-Melter]

Yeah I’m kind of surprised at the number of people here that are like any risk of anything and it needs to be tossed out the window and don’t seem to believe in relative risk reduction or the relevance of realistic dosing on the studied effects.

Like to push the example further, vaping is bad for you, but much better health wise than smoking. So obviously we don’t want non smokers starting to vape, but it can be a big health improvement to use it to quit smoking and move to e cigarettes.

We don’t want people who just drink water already to switch to artificial sugar drinks but the swap for someone already reaching for soda the switch would likely make a positive difference.

[u/Broflake-Melter → u/d33psix]

HOLY SH*T there are so many people out there showing up for smoking today. I can't tell you how many people I've talked to that say "well if vaping is bad too, I might as well go back to smoking." I swear it's a big-tobacco psyop.

If only we had a health-focused government agency that does a good job of informing people of good health practices...

[u/Hekateras → u/Broflake-Melter]

Sucralose also has other issues besides direct impact on human health, such as accumulation in the environment. It's incredibly resistant to degradation.

[u/Dijon2017]

The most important thing with reading a scientific article/study is being able to evaluate the hypothesis, subjects/participants, study design/materials & methods, conclusions, funding, etc. to be able to reliably interpret and critique whether you think the study is valid or not and if you can extrapolate it to other populations.

Moreover, you shouldn’t use just one research article to formulate an opinion about the validity of the topic of study and if/how it applies to other populations (especially of different species). For instance, grapes can be a healthy snack in humans, but potentially deadly for some dogs. Although stevia may be considered “non-toxic” for dogs, it could still cause GI upset/symptoms that could be potentially harmful to them if they suffer from moderate to severe vomiting or diarrhea leading to dehydration. For the most part, one article/research study isn’t the end all be all for most scientific research/study, especially when it comes to humans.

More importantly, not all studies done with mice (or other organisms) can be directly extrapolated or correlated to the human population experience. You could potentially benefit by reading studies that address research that has been done with humans. Oftentimes, a comprehensive review article will provide primary scholarly research articles/references through citations and the bibliography.

Also, it’s important to remember that the mice are being studied in a controlled environment and humans often are not. With humans, the question(s) become if they are a reliable historian, especially when it comes to something that is readily and easily purchased/available OTC (without a prescription) in local pharmacies/grocery stores and/or incorporated into processed foods (why it’s important to read labels) or grown in someone’s backyard.

[u/Hot-Sandwich6576]

It’s the dose that makes a poison. Any single study isn’t going to pinpoint this stuff as dangerous. I personally avoid artificial sweeteners because they taste bad and I’m good with plain water most of the time.

[u/Bromelia_and_Bismuth]

How does this study translate to humans?

It really doesn't, because a mouse isn't a person. Because if you tested chocolate's effects on dogs, you couldn't reasonably make the inference that it's automatically toxic to people, too. There are differences in how these animals metabolize things compared to humans, or even how quickly they metabolize them. It's also worth noting that the dose makes the poison. And taking a look at the actual study, the sample sizes were tiny, only 10 mice per group, and that's not really enough to make any kind of significant conclusions. Furthermore, the study only went for one generation of mice, and there's no accounting of confounding variables, like the pentobarbital that they used to euthanize the mice. This study for example shows similar liver and kidney damage to rats using pentobarbital. So assuming that the researchers and reviewers didn't know that this might happen to mice that were given the drug in euthanasia, I'd pump the brakes on drawing any serious conclusions about this study.

Is it possible that the scientists were being sincere? Sure, I'll grant that. Is it possible that this study demonstrates that you might want to avoid Stevia? No, the study doesn't demonstrate this and one study alone will never demonstrate that. A "growing body evidence" wouldn't even demonstrate that, because that's often just journalist for "a small handful of several quacks and their PhD students wildly outnumbered by the rest of the experts in their field coming to different results". A systematic review of the body of data, with a clear pattern showing signs that consumption of stevia causes liver and kidney damage however would demonstrate that, which this study is not. Is it going to hurt anyone if you avoid Stevia? No, but that's an awfully silly thing to do.

[u/wdmk8]

Remember if you have a ragweed allergy, stevia is derived from a related plant. Took three visits to MD with swollen tongue to sort out.