duffpkg 19 hours ago

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...

  • casualscience 14 hours ago

    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'.

    • esperent 13 hours ago

      > 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?

      • nerdsniper 11 hours ago

        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)

        • esperent 10 hours ago

          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.

          • nerdsniper 9 hours ago

            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...

  • hollerith 18 hours ago

    >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.

    • Moto7451 16 hours ago

      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.

      • hollerith 10 hours ago

        OK. Thanks for explaining.

      • bestouff 16 hours ago

        Alcoholic beverage, just fine ? I disagree.

        • Moto7451 6 hours ago

          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?

        • majkinetor 14 hours ago

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

    • pull_my_finger 5 hours ago

      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.

    • nerdsniper 8 hours ago

      > 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?

  • ethan_smith 18 hours ago

    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.

  • aatd86 13 hours ago

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

jcynix 19 hours ago

”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?

  • heavyset_go 17 hours ago

    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.

    • esperent 12 hours ago

      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.

      • jcynix 8 hours ago

        >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

  • MichealCodes 19 hours ago

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

    • jajko 15 hours ago

      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.

      • MichealCodes 4 hours ago

        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.

      • chownie 11 hours ago

        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.

      • esperent 13 hours ago

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

      • chaostheory 15 hours ago

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

        • majkinetor 14 hours ago

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

  • OutOfHere 18 hours ago

    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.

    • burnt-resistor 16 hours ago

      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.

      • majkinetor 14 hours ago

        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.

      • OutOfHere 10 hours ago

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

    • Eisenstein 18 hours ago

      Can you go into detail about these substances?

      • oarla 18 hours ago

        Maybe the fiber helps?

        • burnt-resistor 16 hours ago

          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.

          • majkinetor 14 hours ago

            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.

MichealCodes 19 hours ago

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

  • ryanmerket 19 hours ago

    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.

    • seec 17 hours ago

      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?

      • amanaplanacanal 8 hours ago

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

  • Bender 10 hours ago

    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.

    • 0_gravitas 7 hours ago

      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.

  • casualscience 15 hours ago

    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.

    • bshacklett 10 hours ago

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

  • OutOfHere 18 hours ago

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

aeze 12 hours ago

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.

  • niffydroid 12 hours ago

    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

mediumsmart 8 hours ago

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?

IcyWindows 20 hours ago

Hmm, the dose seems odd.

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

  • abeyer 17 hours ago

    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.

Eisenstein 18 hours ago

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.

mixwpl0j 19 hours ago

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

  • antonvs 13 hours ago

    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.

  • ben_w 18 hours ago

    "Normal sweeteners" are, in fact, chemicals.

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

    • leptons 14 hours ago

      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.

  • sharifhsn 18 hours ago

    “Normal” sweeteners are also chemicals.

  • hilux 17 hours ago

    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.

westurner 9 hours ago

> 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