Zero calorie sweetener linked to blood clots and heart disease, study finds | Hacker News Reader

Zero calorie sweetener linked to blood clots and heart disease, study finds

cnn.com

46 pointsprmph64 comments

This study really annoys me. I'm doing keto and its helped tremendously including consuming a TON of erythitol. The amount of bad press low carb diets and artificial sugars get don't account for the simple fact that - if they didn't exist people like myself would be WAY worse off. I'll keep taking my chances with these sweeteners vs going back to my old eating ways which would 100% send me to the ER from a heart attack or similar.

I wouldn't get annoyed at the study—they're trying to discover objective facts about the world, and it is very important to know that a commonly-accepted sugar substitute causes a drastic and long-lasting increase in clotting behavior after consumption. What you do with that information is up to you.

To add to that, they seem to have anticipated the OP's reaction since it was mirrored by the Calorie Control Council (industry cartel?) and are literally saying: if the study is sound and if you are worried about clotting or heart disease you need to watch your intake. This is because they claim the amount that was used was the same amount in common sugar-free sodas.

If the OP is saying their intake is way higher than that and that the only way they can reduce that is to return to their old sugar habit and become clinically obese, then yeah, without additional information I guess it's better to stay on sweeteners. But if you're escaping a burning building and are in danger of getting hit by a car when doing so, the course of action is to avoid getting hit by the car -- not run back into the burning building or wait till the car hits you.

If you live in a place with accessible healthcare (easy access, fast appointments, or cheap, depending on your criteria) you should just keep tabs on your heart at least.

You're almost certainly right that consuming artificial sweeteners is orders of magniture healthier for you than it would be to consume the sweetness-equivalent dosage of sugar. The interesting question is whether not consuming artificial sweeteners nor sugar would be significantly healthier than consuming artificial sweeteners in such an amount.

I don't know, erythritol is the one where they found this alarming association when they weren't even expecting it. Couple that with new research showing that the effect occurred *in every subject* and I personally think there's enough evidence to say that there is no known safe amount of erythritol to consume. These studies look extremely different than your typical "hur dur, XYZ is toxic or ABC is a superfood!!!" garbage studies.

I'm both diabetic and have a clotting disorder (among other problems life throws us) and, while I often get annoyed at the press on medical reporting, I don't nearly as often get annoyed at the studies themselves. While it's important to weight the benefits vs the downsides (the piece most media reporting is missing when talking about these matters) we really on studies like this to do that weighing.

Exactly. I'm not annoyed that it might be found to be bad, like that would be great to know. But I want to know, is it worse for me than the alternative (sugar, lets be real).

I don't think there is a way to answer that question beyond indirectly via findings of the ways things are bad from studies like these. E.g. how bad real sugar is for me is going to look like an answer from another planet compared to the same question for my wife.

Why would you need to consume any erythitol at all to be on a keto diet anyway? Doesn't keto mean no or few carbs or no simple carbs or something like that? You can just focus on eating animal proteins, fats, fiber (vegetables) etc. Not sure where sweetener comes into it?

You keep linking "low carb" with "artificial sugars" but I don't think it takes any particular self control to just cut sweeteners of both the natural and artificial kind out.

I can understand if you have some specific recipes that are sweet that you loved from before keto and wanted to just recreate them, but why bother? Why not just switch to recipes that don't need it at all and avoid the hassle? Eat beans, cabbage, beef, eggs, yogurt, the list is endless.

A delicious nutritious varied diet is easy to accomplish without resorting to junk food, processed food, or weird modern chemicals invented recently, so I really don't know why anyone bothers messing around instead of just sticking to the tried and true.

What exactly is so disgusting to you about a nice steak with a side of sauteed green beans and pinto beans? Or an omelette made with cream and avocado and tomato and onion and bacon? Can you really just not stand a nice chicken soup with peas, carrots, onions, garlics, and leeks? Maybe a roasted sweet potato if that isn't too carby for your personal understanding of keto? Mmmmm how about a salad from one of those fast casual salad places with lots of veggies and some roasted chicken, beans, and a good fatty dressing and avocado? I'm getting so hungry!

I've never done keto but I've tried cutting all sweeteners and simple carbs out many times (allowing whole complex grains and tubers like corn, brown rice, potatos) and it's always been easy and required no more will power than the will power needed to actually cook for yourself (with some takeout as feasible, but that depends on your finances and your location-- much of the USA is tough for eating healthy outside of your kitchen)

I'm just baffled by this idea that sweeteners are a necessity. I don't think you have a very broad palate and need to expand it.

> I don't think it takes any particular self control to just cut sweeteners of both the natural and artificial kind out

It does.

I'm going to give this (rather hostile and dismissive) comment the benefit of the doubt, and answer it with the idea that you really don't understand this and that you want to.

>>> Why would you need to consume any erythitol at all to be on a keto diet anyway?

Because making lifestyle changes often involves finding ways to make those changes tolerable within your own levels of motivation and stress-tolerance.

>>> I don't think it takes any particular self control to just cut sweeteners of both the natural and artificial kind out.

It may not for you, but I think it is fair to say that the vast majority of the population wants to eat sweet things sometimes. They would consider it a major quality-of-life loss to not be able to do so.

>>> Why not just switch to recipes that don't need it at all and avoid the hassle?

Perhaps they've tried and haven't found ones they like. Perhaps they're not a skilled cook, or lack the appropriate facilities for good home cooking. Perhaps they don't have a lot of time to cook for themselves, or money to eat out, and they just eat what they've got around.

>>> What exactly is so disgusting to you about a nice steak with a side of sauteed green beans and pinto beans?

Well, speaking for myself: I don't like green beans or pinto beans.

I'd also point out that there is excellent health evidence to suggest the consumption of red meat is detrimental to health. So why aren't you cutting out the steak? (Perhaps because you enjoy the steak and are willing to make some trade-offs of optimum health for personal life enjoyment?)

>>> but I've tried cutting all sweeteners and simple carbs out many times and it's always been easy

Yes, nothing says "it's easy" like "I've tried it many times".

That aside, though: something that is easy for you may not be easy for me or for someone else, and vice-versa. How hard something is is not an objective quantity conserved across all people. The most obvious example of that is physical disability ("going up stairs is so easy? why can't you just stand up and climb?"), but motivational and hedonic needs also vary dramatically from one person to another.

Well no one replying to this thread is a doctor. Maybe the question is, why not go ask a doctor for what to do about diet and exercise related health problems?

I just lost about 130 pounds over the past two years (328 -> 196). It wasn't because I learned something new. It was because I figured out how to actually do the things that I already knew that I should. I didn't even do anything as dramatic as keto. I just ate less and exercised more (and spent time at high altitude, which seems to be a massive factor for me). But the "just" there is doing a lot of work, because actually doing that was really really hard and was the result of nearly a decade of growth and self-improvement in my ability to manage my own behavior.

Nutritional advice is pretty simple, at its basics. Eat a reasonable number of calories, minimize saturated fat and sugar intake, eat red meat sparingly, get some vegetables in there. There's more detail than that (obviously, that's what this thread is about), but that's sufficient for basic health. There's almost no one in the developed world who couldn't give that advice. But we have an obesity epidemic anyway. People know what to do. They just don't do it, and that's a different category of problem.

>People know what to do. They just don't do it, and that's a different category of problem.

Most people dont understand weight loss isn't about Food or Nutrition. It is actually 99% mental model changes. Not to mention the possible depression etc you get while you are at it.

It is like people who want to do Gym and figuring out which Exercise is best for muscle growth etc. But actually getting into the gym is 99% of the job. Without it, you get nothing.

I personally have and am dieting in accordance with my doctor who signed off on my meal plans which include these sweeteners.

That’s the best information to hear. If the goal is weight loss, it is interesting what the conversation could be like today, since GLP-1s are more in the zeitgeist.

The doctor will tell you to eat less calories overall, and reduce your consumption of sugar, by replacing it with better alternatives like calorie-free sweeteners.

honest question, people who use zero calorie sweeteners might also be people who were otherwise engaging in unhealthy habits. For example, fast food workers will tell you that regulars order unhealthy items along with "diet coke" typically. I haven't read this research but do they account for biases like this?

There has been previous observational studies for erythritol, but this was not was not an observational study.

It was straight forward experiment.

They gave small group of people drink with erythritol and observed (P<0.0001) in everyone really big increase in markers for TRAP6 that activates thrombin receptors responsible for the coagulation.

erythritol -> coagulation link was direct. When you combine it with observational studies in larger populations. It harder to explain them away with other habits and conditions.

>The present studies suggest that following ingestion of an artificially sweetened food harboring typical levels of erythritol as artificial sweetener, plasma levels of erythritol remain elevated for many days, well above the thresholds necessary to enhance stimulus-dependent platelet reactivity, even among healthy volunteers. . .This is of concern given that the very subjects for whom artificial sweeteners are marketed (patients with diabetes, obesity, history of CVD and impaired kidney function) are those typically at higher risk for future CVD events https://www.science.org/content/blog-post/trouble-erythritol

Thanks for explaining that. Hard to argue against direct evidence I guess.

Here's [1] a biochemist talking about an erythritol study (didn't check if it's the same one, but it's the same claimed symptom). They controlled for the obvious risk factors (though with the usual caveats that controlling for things is hard), and they have a claimed mechanism of action:

> But we seem to have spotted a toxic effect now. This latest paper shows that plasma erythritol levels actually make a good predictor of major cardiovascular trouble (heart attack/MI, stroke, CV-associated deaths). In 1,157 patients volunteers undergoing three-year longitudinal evaluation, the patients in the highest quartile of plasma erythritol concentration were very strong outliers for CV events. That correlation holds up after controlling for all sorts of other dietary and physical variables (weight, age, gender, known cardiovascular risk factors, and more). And on top of that, the authors demonstrate a surprising but extremely plausible explanation for these findings: erythritol, in both in vitro and in vivo assays, enhances platelet aggregation.

> ...I myself will be studiously avoiding it from here on until someone can convince me it’s safe. You may feel similarly after looking at the evidence.

There are also other studies (same chemist in [2]) claiming the same effect for xylitol, another related sugar alcohol.

-----

[1] https://www.science.org/content/blog-post/trouble-erythritol

[2] https://www.science.org/content/blog-post/and-now-xylitol

They do the best they can, but it’s actually impossible to do the real scientific method with human participants without going all Frankenstein crazy.

Keep in mind these are relatively minor effects, kind of like how not walking for at least an hour a day will shorten your total lifespan by a measurable bit, but people are living so long that only a small number care.

I'm not sure if the premise holds. Most of the people I know who use sugar replacements or consume products with them are from the fitness crowd.

Sure, they might, but I think it could be equally likely that many people who drink it just want to lose weight or not have so much actual sugar, not that they're necessarily already engaging in unhealthy habits.

Choose your poison: sugar is worse, and no sugar is miserable. You'll die anyway, enjoy whatever you want, however you want, whenever you can. It makes no difference in the grand scheme of things.

> no sugar is miserable.

Few weeks. After that steamed carrots taste really sweet. If you drink soft drinks that are extremely sour and sweet, then eat chips for maximum salt and fat taste, you are essentially blinding your taste buds. Everything else tastes bland.

Everyone can habituate. People have lived long time with eating less sweets than we do today and they were not miserable.

> no sugar is miserable

This is very subjective

> You'll die anyway

But you better avoid cancer, dementia etc. Regular consumption of sugar and/or HFCS likely increases the risks.

You don't think there's a medium to be found here?

Sure, denying yourself all pleasures isn't a lot of fun. But living entirely in response to those urges is a great way to feel sick and unhealthy all the time. I feel physically way healthier and better at 196 pounds than I did at 328. That's not just because it's likely added many years to my lifespan. It's because I don't have to check the sturdiness of a chair before sitting down, because I don't want to collapse after climbing a staircase, because I can share my body with a sexual partner and not feel ashamed.

Self-control does not have to mean self-denial. It means making the trade-offs between different things you want (which often conflict with one another) deliberately and consciously instead of accidentally.

Artificial sweeteners are like methadone. Methadone might be less worse for you than heroin, but it’s still something you should avoid if you can.

Yes, mainlining pure sugar all day is an awful habit and a fast path to an ugly death. Yes, kicking that habit with an artificial substitute can be effective. But it’s still a short-term solution.

The food industry isn’t interested in you kicking any habits, though, just transitioning to another of their products. Unfortunately for us all no food is as magnetic to humans as sugar.

I saw this news last year: https://www.nature.com/articles/s41392-023-01504-6

I use a mix of erythritol and xylitol (there is evidence of synergistic effects) to brush my teeth, I use it as a home made mouth wash without swallowing. Not sure how good they are as sweeteners. They are not very sweet and are not suited for baking. Most other artificial sweeteners, except stevia, disrupt your gut microbiome. I think it was this study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10144565/

You say not suited for baking but baked goods is one of the most common use of erythritol and des pretty decent at it IMO.

Never head about this. At least, it won't do much for the taste, except sweetness. You need a reducing sugar to make bread. Cooking is nothing but chemistry!

https://en.wikipedia.org/wiki/Maillard_reaction

Usually you don't replace sugar 1:1 with sweeteners like Erythritol for these kinds of reasons. Sometimes you mix it with other sweeteners to bulk them up and other times you include other non-sweetening agents combined with recipe adjustments to compensate for the lack of certain effects. In general you usually include more erythritol than you would sugar, even with these other things accounted, to get the same level of sweetness (but not a ridiculous amount more, like 40% or so depending on what else you change). That said it's often impossible to get something people like more than real sugar no matter what you use/do ;).

E.g. a Cleveland Clinic article about it which headlines "Erythritol is a common artificial sweetener found in baked goods, beverages, gum and candy" https://newsroom.clevelandclinic.org/2024/08/08/cleveland-cl...

You definitely don't need any added sugar to make bread.

Flour, water, salt, yeast.

I reserve the right to be spectacle about Big Sugar having something to do with funding this kind of research, BUT if it is true, this does kind of suck. Erythritol seems to be THE non-sugar sweetener atm. They put it in everything. So much so, that 90% of specifically otherwise labeled sweeteners, i.e. stevia, monk fruit, allulose etc, are usually "blends" that are mostly erythritol. Check your labels, even brands like Purevia/Truvia which heavily imply that they are "pure - (ste)via" or "true - (ste)via", have erythritol as their primary ingredient. The same is true for the bigger brands like equal/splenda etc. It's hard to find actual stevia or other sweeteners without erythritol.

Consuming a drink with erythritol — an artificial sweetener used to add bulk to stevia and monk fruit and to sweeten low-carb keto products — more than doubled the risk of blood clotting in 10 healthy people, according to a new pilot study.

10 people. not exactly convincing. It reminds me that earlier study about a purported cure for colon cancer which had 8 participants, which no one talks about anymore.

You're ignoring most of the data and mischaracterizing what you did mention.

Is this more convincing?

> That study also analyzed the blood of more than 4,000 people in the United States and Europe and found that those with the highest levels of erythritol were twice as likely to experience a heart attack or stroke.

This is not more convincing because the human body produces erythritol endogenously so high erythritol blood levels may be another effect of the health problems that cause heart attacks and strokes, rather than the cause. To prove causation they would have to track each subjects consumption of erythritol rather than their blood levels.

The referenced study's methods did NOT account for the fact that overweight people are more likely to be consuming erythritol and/or on a keto diet. Highly likely to be confounding.

How does one measure "double the risk"? Does that mean if one person in a control group happened to have a stroke in that time period, and now it's two people, that counts as double? Out of 4000? Surely that can't be right.

n=1 can be important if the effect size is good. What makes this n=10 (per group) is interesting and not insignificant is that there is 100% response for blood platelets "enhanced stimulus-dependent release of the platelet dense granule marker serotonin (P<0.0001 for TRAP6 [thrombin activator peptide 6] and P=0.004 for ADP) and the platelet α-granule marker CXCL4 (C-X-C motif ligand-4; P<0.0001 for TRAP6 and P=0.06 for ADP)"

There are other studies n = 1,157, n = 2,149, n = 833 and article links to some of them.

See my other comment to see better discussion and links to studies.

That person could have other unknown problems though... I find it hard to believe that 1 person can ever be enough to quantify anything.

If you give one person rare substance X and that person dies 40 minutes later, it's enough. P < 0.000001 or at least, because people dying in 40 min time period for unrelated reason is really rare.

This study was an experiment (P<0.0001) that directly observed blood coagulation markers. Drink -> coagulation.

It's still an improvement on top of studies that just used serum levels (your body can generate some sugar alcohols, so may not be as closely related to consumption as one would think).

Wait, so they added 30g of erythritol and observed negative impacts? Most the time I see it around 7g plus other sweeteners. It’s almost never alone now.

I bet they need to look at 30-45g sugar harder now. Maybe uncover some of that (big sugar suppressed) research that it causes heart disease.

Note that this is about erythritol specifically. The actual study: https://www.ahajournals.org/doi/10.1161/ATVBAHA.124.321019

If true, this is extremely frustrating. While on the Keto diet I researched a whole bunch of “bad” sweeteners based on sugar alcohols that affected your blood sugar level, and erythritol always came out as one of the good guys.

Allulose is looking better every day, so many more upsides with very few negatives (mainly expensive)

https://www.youtube.com/watch?v=4SCaRG3jqS0

Discussion of this topic from the most balanced and nuanced source I've seen.

Here is good discussion about sweeteners from Derek Lowe:

Trouble With Erythritol https://www.science.org/content/blog-post/trouble-erythritol

Sugar Substitutes Surprise https://www.science.org/content/blog-post/sugar-substitutes-...

And Now Xylitol https://www.science.org/content/blog-post/and-now-xylitol

It seem that most artificial sweeteners have issues. But interestingly aspartame is probably the least harmful, if not for other reason than being so sweet that you need much less of the molecule, and get always low dose.

> .... At any rate, I would regard these studies as reason enough to avoid both of these compounds as sweeteners, and I would extend the caution to the other sugar alcohols as well (maltitol, mannitol, sorbitol, etc.) We really need to understand more about these things, and ditching the sugar-free gummy candies and the like seems like a prudent move.

>Naturally, the question comes up about the effects of other artificial sweeteners. I also wrote last year about a study that showed that saccharin and sucralose seem to have unexpected effects on glucose tolerance, but aspartame and stevia did not show this. One difference between some of these and the sugar alcohols is that things like aspartame (and acesulfam-K) are far, far sweeter than sugar and are thus used in much lower amounts. You don't have the gut-fermentation aspect the way you do with the quantities of sugar alcohols that are needed.

>Note that I am discounting the years of hyperventilating messages about aspartame (in particular) leading to supposedly sweeping epidemics of cancer, autism, seizures and what have you. These are not based on any solid evidence, and after the original trials and forty years on the worldwide market, there would be solid evidence by now if any such things were happening.

>No, for bad effects coming from artificial sweeteners, I would look to just kinds of things we're talking about now: slight impairments or increases in trouble in areas that many likely customers for lower-calorie foods already would be experiencing trouble with (glucose tolerance, cardiovascular effects). This makes such things harder to spot in a population; you need a good amount of effort in well-powered trials to believe that they're there at all (the glucose tolerance results are in need of this for more validation, I should add). Let's find out what's going on.

Sucralose is also extremely potent, for what it’s worth, so that you only have to use a tiny amount of it.

It’s one thing you have to look out for in studies on the health effects of a lot of artificial sweeteners, particularly in animals. The doses might look reasonable at first glance, but are often orders of magnitude greater than anyone would actually consume.

(This doesn’t apply to sugar alcohols, mind you, which tend to have a similar or even lesser sweetness to sugar.)

> saccharin and sucralose significantly impaired glycemic response,

> each bulked out with glucose to an equivalent size

Meaning that the packets were more or less pure glucose.

No.

Yes. Read the actual study. And ask yourself, why on earth, with all the possible vehicles out there, someone would choose 20% of the typical RDI of glucose for a study on the effect of a sweetener on glucose tolerance. If they were going out of their way to find the most confounding vehicle possible, they’d have been hard pressed to find a better choice.

> aspartame is probably the least harmful

I'm not doubting you, but it's interesting because this is the only one that gives me noticeable problems, although for decades I had no issue with it. Then one day it just started where any time I try to drink a diet soda (with aspartame), I now get massive headaches... no idea why.

Oh wow, me too! I thought I was the only one. I can't drink a diet coke without getting a mild headache.

I also get headaches after consuming aspartame, and they are more severe than a normal headache, and come on about 30 minutes after drinking it, consistently.

now if only neotame was mass produced.. (100x aspartame's potency but requires more synthetic steps to reach)

You can get neotame online, including on Amazon. I really dislike it though. Its sweetness has a very strange attack and decay, if that makes sense, so that there isn’t really a right amount to use where it won’t taste some combination of too sweet and not sweet enough over the course of a bite or sip.

Neotame is cool stuff, I bought a packet online and it's wild. Ultimately, I went back to stevia which is fine for my purposes.

Does it pose any risk to people with healthy cardiovascular systems (perfect BMI)?

n = 10, these links probably warrant more research and a larger cohort.

That’s disappointing because zero calorie sweeteners and products that use them are a game changer for those who need to manage calorie intake or glucose levels.

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