Erythritol linked to brain cell damage and stroke risk | Hacker News Reader

Erythritol linked to brain cell damage and stroke risk

sciencedaily.com

94 pointsOutOfHere91 comments

This is a study done on cell cultures. It should NOT be used to influence behaviors regarding human health. The article linked makes a lot of leaps not supported by the study itself.

Link to actual study: https://journals.physiology.org/doi/full/10.1152/japplphysio...

>It should NOT be used to influence behaviors regarding human health.

It's not like erythritol is hard for a consumer to avoid. P(serious problems like brain cell damage) does not need to get very high for it to start to make sense to avoid it, and it seems to me that studies done on cell culture can raise P high enough.

The test setup ignores the digestive system. There are going to be a lot of substances you can pour on a culture of brain cells with negative affect that your body produces or happily consumes. That’s the point of the parent.

Add milk, an alcoholic beverage, or some lemon juice and those cells are unlikely to survive. Meanwhile the standard path of consumption handles the situation just fine before your brain is ever involved in metabolism.

Alcoholic beverage, just fine ? I disagree.

Learn about hormesis then and don't succumb to the yt's med-bros click-bait hype

Jeez, what a dismissive (and handwaivy) response.

Alcohol is a carcinogen, and even small amounts are linked to increased cancer rates[1][2].

The only thing the WHO, CDC, and US Surgeon General have in common with the “YouTuber med bros click bait hype” you try to wholly discredit is that they probably all do have YouTube channels…

[1]https://www.hhs.gov/sites/default/files/oash-alcohol-cancer-...

[2]https://www.who.int/europe/news/item/04-01-2023-no-level-of-...

Jeez, learn to read and learn and stop with this BS already:

From your first article:

> The amount of alcohol a person drinks affects their risk of cancer. An important factor is the overall amount of alcohol consumed consistently over time.

That, sure as hell, means that you can drink small amounts sometimes, not 0, as there is no such thing. Again, read about hormesis. Here it is for you:

https://en.wikipedia.org/wiki/Hormesis#Alcohol

How about Kombucha? Vanilla extract? Sourdough bread? Mouth wash? Oral medicines? There are more sources to alcohol than the bar, including many incidental sources we don’t think about and happily feed to children as soon as they can handle solid foods.

Like anything there’s nuance here. I’m not saying being drunk, an alcoholic, or having a single alcoholic beverage will have no negative affects. I’m discussing the difference between a culture (cells on agar) and the entirety of the human body. You are not going to reproduce the same results they had because your digestive tract, kidneys, and liver are inline.

This is really important because our food contains so many things naturally including the Erythritol in the original article.

Let’s talk about another example. Would you find Fish acceptable? How about mercury? How would you square exposure to mercury due to eating fish?

OK. Thanks for explaining.

To the reader, I strongly urge not listening to some rando on the internet (as opposed to the scientists) who asks you to dismiss a study, simply because the risk-reward calculus here is strongly in favor of not taking the unnecessary risk of brain damage.

> It's not like erythritol is hard for a consumer to avoid.

How many ingredients with negative effects on the order of erythritol are in my foods, cosmetic products, homecare products, food packaging, etc that I need to be aware of? Not how hard is it to avoid erythritol -- but how hard is it to avoid every substance that is at least similarly bad for me?

Well, you're always welcome to be reckless and kill yourself faster if that's your goal. Just don't expect others to be equally reckless.

To answer your question, no, it is not hard to avoid the labeled harmful substances that one knows are harmful.

Friends who have (genuine, medically diagnosed) health problems with gluten or soy would disagree.

It actually is. If you're shopping low carb/keto marketed stuff, they put it in almost everything. Even other sweeteners like stevia, monkfruit, allulose often are cut with majority erythritol. You have to really scour the packaging to make sure you're buying "stevia" and not a "stevia blend" etc. Erythritol sucks too. It gives a weird cooling sensation on your tongue like menthol, I have no idea why they mix it into everything.

Because it has no calories. Xylitol is nicer but gets metabolized. Erythritol is one of the few sweeteners that are reasonable to use at home (like, you can dose it like sugar unlike aspartame), tastes reasonable on its own (you don’t need the blend you have in coke zero for example) and will not spike glucose levels so diabetics can actually use it.

Like, I can bake a cheese cake just like any other cheese cake as long as I replace the flour for the bottom with almond flour and the sugar with erythritol.

We do a lot of keto cooking here. Erythritol is the bottom of the barrel. They have monkfruit/allulose blends that are very comparable to sugar in taste and how they interact with heat - caramelization or melting in granular or powdered. I've read erythritol is more "immediately" sweet on your tongue, but for it's "potential" health detriment, as well as the overpowering "cooling" effect it's really not worth it. I guess if you're doing low cal as well you need to make additional concessions but most of those that don't get processed, really turn your GI upside down as well.

In vitro studies demonstrate potential mechanisms but cannot establish causality in humans due to differences in metabolism, bioavailability, and the blood-brain barrier's protective effects.

Aka: https://xkcd.com/1217/

If you poured distilled water on cells in culture they'd also all die.

Drinking distilled water will also kill oneself, just slowly. This is because it is demineralized and it can become acidic. It also risks leeching and dissolving heavy metals from foods, risking their increased absorption.

This sounds like a smart comment, but the main reason you shouldn't take in vitro studies as indicative of real medical outcomes is largely due to unknown bio availability when consuming realistic doses. However, this study shows that the concentration of erithritol is well above the concentration where they see negative effects in vitro when consuming a realistic dose.

In addition epidemiological studies have found associations between higher plasma erythritol and clotting/cardiovascular events. So, regular disclaimers about difficulty of establishing health science aside, I would disagree this should 'not influence behaviors'.

> However, this study shows that the concentration of erithritol is well above the concentration where they see negative effects in vitro when consuming a realistic dose.

Are you saying that when you eat a normal/largish amount of erithritol (say 1-10g), the concentration of erithritol in your brain is similar to what they tested on brain cells in vitro here?

Also, how can they make a link to stroke when testing in vitro?

The study used a concentration of 6mM erythritol. This would be the mean (“bulk”) concentration found in the body after drinking 2-3 erythritol-sweetened soft drinks. I can find several with 10+ grams of it per bottle/can.

Erythritol Concentration: 6 mM (0.006 mol/L)

Molar Mass of Erythritol: 122.12 g/mol

Water in human body: 42 Liters

Calculated Total Mass: 30.77 grams (0.006 * 122.12 * 42)

You're assuming that:

A) all of the erithritol consumed ends up in serum (blood)

B) is equally distributed throughout all the blood in the body

C) entirely bypasses the blood brain barrier

These are huge assumptions. A) is certainly wrong.

A) Erythritol has ~90% bioavailability. See note at bottom.

B) Is a reasonable assumption. See same note at bottom.

C) Erythritol damages the microvascular endothelial cells, which form the BBB. So it doesn't need to cross the BBB, because that's what it damages directly. The name of TFA's study is "The non-nutritive sweetener erythritol adversely affects brain microvascular endothelial cell function"[0].

N.B. Erythritol is known to pass through the BBB via diffusion, though that's somewhat limited by its partition coefficient (logP) of -2.3. It's a small molecule, so it's not blocked based on size.

Also, this study isn't "just one study". There's a large corpus of research accumulating data both in vivo and in vitro showing both that erythritol causes these problems, and demonstrating how. This was a very thoughtful and reasonable study. The main point of the study was to measure oxidative stress, nitric oxide (NO), endothelin (ET)-1, and tissue-type plasminogen activator (t-PA). Their dysregulation is already well-known to be directly linked to the health of brain blood vessels and shown to be quite relevant in the development of stroke.

Epidemiological studies involving thousands of patients first established a strong, independent link between higher blood levels of erythritol and an increased risk for events like heart attack and stroke[1]. Subsequent mechanistic studies then showed that erythritol makes blood platelets hyper-reactive and more prone to clotting, providing a direct link to thrombosis[2]

Also in response to:

> A) is certainly wrong.

A previous study gave participants 30g of erythritol orally and their serum concentration rose from 4 µM to 6,480 µM [3]. That's why this study chose 6mM - they didn't just do some napkin math and YOLO it - previous studies pointed the way after showing that "(A) is certainly right".

[0] https://journals.physiology.org/doi/full/10.1152/japplphysio...

[1] https://pubmed.ncbi.nlm.nih.gov/36849732/

[2] https://www.ahajournals.org/doi/10.1161/ATVBAHA.124.321019

[3] https://consultqd.clevelandclinic.org/evidence-mounts-that-s...

Because we are not composed of cells, right? (in jest)

To the reader, I strongly urge not listening to some rando on the internet (in opposition to the scientists) who asks you to dismiss a study, because the risk-reward calculus here is strongly in favor of not taking the unnecessary risk of brain damage.

It's a bit of Pascal's Wager, isn't it?

Seeing as this is an in vitro study, they fall back on a specific human study (Witkowski et al., 2023) for many of the human effect claims. However the referenced study has a few issues:

- All study subjects had a "high prevalence of CVD [cardiovascular disease] and risk factor burden"

- Erythritol occurs naturally in the body and and this was not accounted for

- The study subjects were already suffering from cardiovascular disease and were likely to be consuming more artificial sweeteners than a general population, but this was not recognized or accounted for

- Erythritol's presence after a cardiovascular incident could be from consumption or from natural production but only baseline was measured despite data showing dramatic fluctuations after consumption

Another one of the studies cited for evidence of human claims (Khafagy et al., 2024) directly contradicts them. It stated said "we did not find supportive evidence from MR that erythritol increases cardiometabolic disease".

There are two more human studies referenced but I didn't read them.

”Erythritol occurs naturally in some fruit and fermented foods." https://en.wikipedia.org/wiki/Erythritol

The German Wikipedia article says it appears naturally in cheese, funghi, plums, strawberries and pistachios. So maybe the lab experiment might be a bit artifial, or the dose much higher than from normal consumption if the above?

The concern is more unnatural consumption. Some use it as a sugar replacement in drinks and foods.

There is also the topic of erythritol-induced diarrhea in higher consumption.

Its almost like these days people are desperately grasping for anything that will deliver weight loss, apart from changing their longterm unhealthy fucking eating habits. US is a long term champion but it has slowly crept into most cultures, just not at that scale yet.

Food portion size, its composition and breaking some sweat regularly works wonders but nobody ain't got time or willpower for that.

Going on a tangent, another natural sugar alternative called allulose also induces diarrhea in higher doses.

So does the Vitamin C. Not sure what is your point.

The mechanism by which alternative sweeteners work induces diarrhea or other abdominal issues.

Note that erithritol has a much lower laxative effect than other sugar alcohols.

Migrants who move to the US skinny on average gain weight, and these are people who have good eating habits and willpower. When 30% are obese and 60% overall are overweight, willpower and individual responsibility are not the tools for the job.

I'd be looking at breaking up food conglomerates first personally.

Ah, the "willpower" myth.

No study has been able to objectively define "willpower" in such a way that doesn't include eating habits, but does correlate with body fat percentage. IOW: If you define "willpower" as the ability to avoid obesity, then yes, it is related to obesity, but otherwise it is not.

See also addiction.

Anecdotally, I have not experienced diarrhea with consumption up to 100g of erythritol in a day. I also do not consume it for weight loss purposes but as a sugar replacement because sugar causes inflammatory immune system reactions in my body.

In natural foods, there are other substances that balance out the harm, making it healthy overall. These other substances are absent when it's used as an additive.

Can you go into detail about these substances?

Maybe the fiber helps?

Fiber is great for gut health but it's actually works against nutrient absorption. Increasing fiber intake requires increasing intake of certain vitamins, possibly with supplementation.

It's better to eat things in moderation and know what antinutrients are in what foods. There are tradeoffs.

Exactly. Fiber sucks up some nutrients so they are either pooped out due to limited digestibility of the colon, or get consumed by gut bacteria.

Fruits have fiber, polyphenols, and rare sugars. I don't know which of these helps control the risk.

You are invoking a fallacy known as 'begging the question' in that statement because you never establish that any of those things control the risk, just that they exist in fruit.

No, I'm sorry but that's not correct. "Natural" is a meaningless health and wellness buzzword that handwaves away the details that each food comes with benefits and disadvantages. There are variable amounts of anti-nutrients almost every "natural" ingredient, some of which we process or cook to lessen them.

Indigenous people processed acorns to remove tanins.

Kidney beans (and many other legumes to variably lesser degree) naturally contain phytohaemagglutinins (PHA-E) which cause red blood cells to clump together. These can be reduces several orders of magnitude by repeated cooking, washing, and draining.

Men shouldn't eat too much soy or chia seeds. Small amounts of chia seeds are fine.

Most adults are lactose intolerant unless they have lactase persistence genes.

Spinach, pepper (the spice kind), rhubarb, almonds, and more contain oxalate that can lead to kidney stone formation. Excess vitamin C does also. Increasing citrate intake helps prevent calcium kidney stone formation, but doesn't help with oxalate kidney stones as much.

The list of antinutrients is long. Don't overdo eating one "natural" ingredient or another because that's the greatest risk of becoming a Chubbyemu video subject.

Exactly. Nature is there mostly to kill you, that is only natural, and thinking otherwise is basically resorting to divine. No living being wants to be food. There can be symbiotic behavior and plants can produce certain chemicals that attract animals that do some things for them like helping reproduction, but its huge stretch to claim that evolution optimizes for health by proxy. Most off beneficial effects of plant chemicals are due to shared pathways and hormesis.

I was referring to the fruits which may contain a tiny amount of erythritol, not to your random list.

The dose people use for sweetener can be 1,000x - 10,000x the amount you'd find in fruit. There's micro to milligrams of it in some foods, people eat anywhere between 3g to 20g+ if they're eating goods baked with it as a sugar replacement.

Erithritol is also produced endogenously from glucose in the lower intestine of humans.

I'm struggling to find a good source on this right now but I remember reading that it could be as high as 10% of all glucose is converted this way.

>We report a previously unrecognized metabolism of glucose to erythritol, and given the association between erythritol and weight gain, research is needed to understand whether and how this pathway contributes to weight gain risk.

Erythritol is a pentose-phosphate pathway metabolite and associated with adiposity gain in young adults | PNAS https://www.pnas.org/doi/full/10.1073/pnas.1620079114

Arsenic appears naturally in many foods. It's a heavy metal that occurs in varying amounts in the environment; albeit almost never at toxic levels.

Dosage is still a thing.

I've consumed large amounts of erythritol for probably 10+ years. What should I watch for? Blood pressure?

Unless you're a cell, this study isn't super relevant to you.

* It does not show human harm, only cellular disruption.

* It uses an unnatural exposure method.

* It builds on epidemiological correlations that may be reverse causality.

* It does not account for systemic factors, metabolism, or adaptive responses.

Yes the conclusion is baffling.

As you say I believe the correlation is reverse causality. It's much more likely that people who consume stuff with "artificial" sweetener are already at risk for stroke than the other way around.

If you don't have weight/cardio problems it is weird to consume "sugar-free" stuff and associated because they are almost always worse tasting than the real deal.

To have any importance they would need a big population sample and correct for already existing risks for stroke and I believe they would find that this stuff has very little impact, if any.

But as always, it doesn't cost much to limit consumption, so why not?

This doesn't apply to a study done in cell cultures.

To the reader, I strongly and vehemently urge not listening to some rando on the internet (as opposed to the scientists) who asks you to dismiss a study, because the risk-reward calculus here is strongly in favor of not taking the unnecessary risk of brain damage. The rando will not be around to look after you after you get brain damage.

I also urge the reader to not assume a lab experiment produces solid nutritional guidance.

Lots of things kill cancer cells in petri dishes that have proven to be useless as medicines.

And your repeated ad hominim "rando on the internet" is counter to good dialectic.

The stroke risk alone is sufficient to not take it.

Unlike with treating cancer, there is no meaningful reward here. As I noted, the risk-reward favors not taking it.

The possible truth is less important here than the possible consequence.

I would discontinue it immediately, then focus on optimizing overall health, just as everyone else.

blood clots: https://www.nature.com/articles/s41591-023-02223-9.

Evidence in vitro suggests enhanced platelet activity. Plasma levels of erythritol are sustained for >2d above thresholds associated with platelet hyper-reactivity after consumption of realistic doses.

I use artificial sweeteners, but prefer sucralose or anything else to erythritol. I actually don't understand why people still use it (often in 'health food' because it's seen as 'natural'), there are much safer options.

Anecdotally, I have preferred it to sucralose, because sucralose leaves an aftertaste akin to gargling with liquid plastic.

That's not even an anecdote; it's a taste preference, and that's fine.

I can not speak to this study, just my own anecdotal experience. I consumed sugar free monsters erythritol for a long time and it now causes pain level 2 in my left temple and visual auras in my left eye if I consume more than two cans in a day its not the 142mg of caffeine before someone suggests it. There is a coconut water at the grocery store that has 20G of erythritol and that will quickly give me a powerful kaleidoscope visual aura that lasts for a couple hours. I can make it go away faster if I lay down in a cool dark room.

Not dismissing your experience, in fact, quite the opposite:

I think you should talk to some doctors about this; I've never heard of anything like this before, and I know that when odd vision/eye-stuff is concerned, it can sometimes warrant a visit to a neurologist.

I appreciate the input. I just avoid having hard amounts of erythritol as do many others like me. In my experience doctors just give me blank stares, talk fast and send me away. I am pretty much done with the medical business. I will be fine.

My point being that it might not be purely due to erythritol itself, and they're might be something else underlying that only (currently) manifests clearly when exposed to it.

I get it. In my experience with the medial business and especially with the "doctors" in my area this is how it would play out:

- They ask a series of questions trying to determine if the issues are a risk to myself or others.

- If it's serious enough they may do a series of the wrong scans.

- They prescribe me some drugs and send me on my way.

Even if by some bizarre chance I had real neurologists and lets say they find something, then what? Statistically my chances of mortality go up the moment I enter the OR and that is even before they attempt to fix something. If the issue is not getting worse I prefer to accept the risk rather than compounding it by letting people confidently act like they know what they are doing. Now if some day it starts getting worse and especially if it gets in the way of normal daily life then I might consider it but even then I would likely leave the country to get better treatment and reduced risk of mortality. In the mean time I keep an eye on the sub-set of people with the same condition the numbers appear to be growing and see how it plays out for them. As of now I suspect it will play out like tinnitus; in that, it will be loosely studied but nobody will know what to do with it or ever fully understand it.

I know that I sound jaded. I am. That train has left the station. I've been abused by the medical business far too long. In my unwavering opinion the entire thing needs to be completely wiped and re-created by entirely different people but that is a 42 volume set of books for another day.

Your experience deserves a proper evaluation by a neurologist, including several tests/scans. You don't want to risk seizures down the road - they can cause significant damage and even kill. A proper course of memantine for up to three months probably also won't hurt.

Oddly erythritol is one of the few things I'm allergic to - it causes me to break out in hives.

Since I have to watch out for it, I've noticed it's becoming more and more common as a sweetener.

I find it flare IBS. Which means anything with Stevia I can't have as it appears erythritol is used, I think, as a bulking agent

I found a Stevia product, White Stevia, in my local organic market. It has maltodextrin added, but that's it. The downside is it's not measure-for-measure with sugar (1/6 tsp vs 1 tsp sugar).

https://www.nunaturals.com/products/stevia-white-stevia-powd...

There are plenty of pure stevia powder products. They don't need to be 1:1 for sugar. I am okay with using the tiniest fractional teaspoons to dispense pure stevia.

Hmm, the dose seems odd.

Would the whole drink amount really all be given to those cells?

I could be off, my molar math is pretty rusty, but a back of the envelope stab seems like 6mM concentration would be _way_ below the 30g "serving" in a drink so assume their "equivalent of" is taking into account the concentrations estimated in the body after consumption or some such.

Right but, what are the odds you aren't all that healthy to begin with if you decide to swap normal sweeteners for chemicals?

Plenty of "fit" products like Quest protein bars use them

https://www.samsclub.com/p/quest-protein-bar-variety-chocola...

and specifically in that high risk group, those chemicals are correlated with an even higher rate of cardiovascular issues than baseline

https://www.nature.com/articles/s41392-023-01504-6

“Normal” sweeteners are also chemicals.

"Normal sweeteners" are, in fact, chemicals.

For example erythritol itself occurs naturally in some fruit and fermented foods, making it a "normal sweetener".

It's only present in miniscule amounts in fruit and other produce. As a sweetener it's 1000x to 10000x more concentrated, which puts it in a completely different context.

Probably a significant majority of Americans use sugar substitutes.

Of course, a significant majority of Americans aren't all that healthy - I guess I'm not sure what your point is.

Using traditional sugar as a sweetener is well established as having negative effects, including inflammation. Many of the alternative sweeteners have a much lower glycemic index, so are thought to be healthier than ordinary sugar in that respect.

If you regularly consume ordinary sugar, you may be in the “not that healthy to begin with” category yourself.

Are you trying to justify erythritol on the basis of inflammation from sugar -- because you can't.

Stevia is a wholly suitable alternative, although its taste and dosing takes some getting used to. Good quality honey in moderation is also fine if the HbA1c stays optimal.

I wasn't trying to justify erythritol specifically, I was responding to this statement:

> "you aren't all that healthy to begin with if you decide to swap normal sweeteners for chemicals?"

I'm pointing out that there are health issues for everybody with "normal sweeteners", so choosing to substitute them doesn't imply that "you aren't all that healthy to begin with".

> erythritol is a sugar alcohol

From https://news.ycombinator.com/item?id=43299867 :

>> "Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming" (2016) https://www.science.org/doi/10.1126/scitranslmed.aad6100

>> "Powdered Booze Could Fix Your Clogged Arteries" (2016) https://www.popsci.com/compound-in-powdered-alcohol-can-also...

> FWIU, beta-cyclodextrin is already FDA approved, and injection of betacyclodextrin reversed arterio/atherosclerosis; possibly because our arteries are caked with sugar alcohol and beta-cyclodextrin absorbs alcohol

How would you compare it with alpha-cyclodextrin? Are these available in good quality on Amazon?

Have you been taking beta-cyclodextrin for a while? In what dose?

I have never taken beta cyclodextrin for any indication. I thought I would relay the study and that it's already approved for human use.

FWIU when the sugar industry maligned fat in the US in the TODO, food manufacturers replaced fat in "reduced fat" foods with fake sugar substitutes which each have harms, high fructose corn syrup, or molasses.

What percentage of cardiovascular "plaque" is sugar alcohol and thus apparently treatable with β or α cyclodextrin, in controls and patients with conditions like Arteriosclerosis and Atherosclerosis?

But you need some brain damage a priori to even consider drinking sugary waters or consuming sweeteners etc. How else are you going to risk a stroke?

I used to inadvertently get erythritol from Quest protein bars, even though I never desired the sweetener. I now regret it.

no regrets, never too late to change the diet :) all the things I would have to regret ... here listen to jamnadas and judge for yourself:

https://www.youtube.com/watch?v=RuOvn4UqznU

Reply on news.ycombinator.com