Too bad this is behind a paywall:
https://www.nature.com/articles/s41591-023-02223-9
Most of the first part of the abstract is correlation, but they get to in vivo (in people) studies of “heightened platelet reactivity and thrombosis potential”. Not sure what those are, though, since it’s behind a paywall.
Thanks. They let you look at it, but not download it. Interesting
Also interesting that their “in vivo” studies were in vitro (whole blood) or in mice. What the actual cr*p is this? That’s not “in vivo”.
And all of fig. 2 can be assume to be correlation, not causation. And if you look at fig. 1, Q1, Q2, and Q3 are all basically the same, while Q4 is way worse. This means to me that the action of erythritol is not linear and in fact the people eating the highest amount of erythritol are probably doing so because they are the worst off. That is, people trying to lose a lot of weight and probably with not great habits.
If I understand the (convoluted) Abstract’s recap of the hazard ratio findings, the lowest quartile vs the highest quartile had an elevated frequency of a cardiac event as follows: 1.80% (lowest quartile of consumption) vs 2.21% (highest quartile of consumption).
These results were obtained from subjects enrolled in voluntary heart monitoring clinics - i.e., likely with pre-existing metabolic/CVD issues.
I interpret this as follows:
98.20% (= 100.00% - 1.80% HR) of those with CVD concerns consuming the least (quartile) amount of erythritol did so without CVD incident.
Whereas, 97.79% (= 100.00% - 2.21% HR) of those with CVD concerns consuming the most (quartile) erythritol did so without incident.
As such, among those who consume erythritol while accessing heart disease-oriented health centers, there was minimal change in CVD event risk across the full range of artificial sweetener consumption levels.
In short, the vast majority of subjects at either extreme of consumption had no cardiac incident - i.e., approx 98% regardless of consumption level.
PLEASE CORRECT ME IF I’M MISSING SOMETHING HERE: Unfortunately, this study doesn’t appear to compare the risks of consuming erythritol against the alternative - that of consuming NONE of the sweetener. This would presumably be a more relevant comparison? (Especially if the hypothesis is that erythritol is not safe for heart health?)
To extend @ctviggen’s suggestion above: For those trying to lose significant weight in the face of CVD concerns, if replacing refined sugar with this artificial sweetener helps achieve meaningful weight loss, this study appears to support the notion that the CVD risk of doing so would be fairly minuscule compared to the broader known health risks of sugar/obesity.
I also wonder since the difference between 2.21% and 1.8% is only .41%, wouldn’t difference most likely be in the noise?
This is now what happens in science today generally speaking. They publish before it’s debated amongst their peers and then it gets picked up by some news org. as being the gospel. I am not saying this is the case with this study but, the study has revealed only a correlation, not causation. The lead author Dr. Stanley Hazen is very good and I have read a few of his papers and have viewed some of his YouTube videos. He published more than 400 peer-reviewed articles and he has over 50 patents from his pioneering discoveries in atherosclerosis and inflammatory disease. Dr. Hazen made the discovery linking microbial pathways to the pathogenesis of cardiovascular disease.(Gut microbiome)
That’s the main problem with a lot of these studies: even when the difference is statistically significant, the clinical effect is usually minimal. I don’t know if Dr. Bradford-Hill actually said it or not, but he is quoted as saying that unless the hazard ratio is at least 2.0, it’s not worth getting out of bed for.
The hazard ratio for Q4 is between 2-3, but the problem is that the HR for the others (Q1-Q3) are basically one. So, what’s different about those people in Q4?
I guess it’s possible that you have to get to a certain amount of Erythritol before an effect happens, but the lack of a dose-response relationship is concerning.
And if you measure blood levels of Erythritol in humans based on tests done in blood in a test tube or mice, I think you need more information. And even if it’s based on the people in Q4, that’s correlational data, not causational.
Then consider someone like me. I almost never eat Erythritol, but sometimes I do. I’ve been eating a little more lately, but it’s really not a lot. If I’m in Q1-Q3, I seem to be OK. It’s only Q4 where (the correlational data appears to indicate) it’s bad.
Indeed. The 95% confidence limits (high and low range) surrounding each of these two averages are wide enough to include both of these averages.
As @PaulL notes, statistical significance is different from meaningful practical world results.
E.g., if we could reduce fender bender car accidents by a very statistically meaningful precise amount of 0.001% by lowering all speed limits by 15 MPH, this would arguably not be a wise idea - for lots of reasons.
In this example, given how minimal the benefits would be - while deemed to be statistically significant - lowering the speed limit would be a poor risk/benefit trade-off by most measures.
As such, I see this study as validation for folks who are earnest about addressing obesity and metabolic syndrome by losing weight… they would be WELL advised to substitute erythritol for refined sugar and HFCS because the real benefits are well-documented and the associated risks are shown by this study to be de minimis. Science! 
I’ve always been suspicious of Erythritol. Has a chemical like taste me. I’m not surprised it’s all over the news now. Just asking for blast ass if you consume it.
As I think I’ve said here before that I pretty much detest what I call the “he-who” studies we see all the time. (He-who eats whatever gets bad thing). I also tend to take a quick look at the results and dismiss them because the effect is too small. If not, a look at how the test was done, food frequency recall tests get a lot of other studies thrown out.
This morning I saw this study in the news that got my attention. It associates consumption of erythritol with cardiovascular events. That link allowed me to read the study but not to save it as a pdf to read at my leisure. I haven’t read the whole thing word for word.
As far as this kind of study goes, it’s pretty well done. It’s only about 3,000 subjects, 2,149 US and 833 in EU, but instead of a result like a few percent or maybe 20% relative risk increase, it shows almost double the risk for Major Adverse Cardiovascular Events (MACE - I’ve never seen that term) such as heart attack (fatal or non-fatal) or stroke. It doesn’t say anything about recall surveys.
Maybe most importantly (as a study) there were experiments done on much smaller groups of people that seem to be controlled, if not actual RCTs (I can’t tell from my skimming).
They specifically say it’s association and can’t prove causation, and they try to show the make up of the groups: things like age, BMI, history of heart disease, diabetes and more.
I use erythritol, typically 3 teaspoons in a day. Seeing basically a 2x risk for these things makes me wonder if there’s a dose response, and there are tests done with “Platelet-Rich Plasma” that do show a dose dependent response; that is, the more erythritol consumed the stronger the response.
I’m not sure if I’m going to change my use of erythritol just based on this, but I thought I’d post it to see what others thought of this. I know some of you are really good at this sort of question.
@CFLBob I moved this post into the other thread. You might want to take a quick read through, to see if what’s already been posted is helpful.
That was my first thought. You can’t just say something had a double chance without the dose 
I eat erythritol, xylitol and a few nice tasting sugars. On my normal, carnivore(-ish) day the amount is zero, on a very very erythritol-rich day (quite rare) it’s maybe 5g… I probably will have less than 1g per month longer term (now I am a bit higher, no idea where exactly though) and it surely isn’t the same as eating it galore all the time
I’m mostly confused how I didn’t find it when I was looking to see if there was already a conversation on this topic. It’s not like it’s an old conversation. I didn’t use the search tool, just looked under Show Me the Science and the Food headings.
The link at the top of this page has “/t” before the thread title. Taking the title off the URL, so it just ends in /t doesn’t allow me to see a page. What subgroup is this under?
Thanks for that. I hadn’t figured out what the different quartiles were for just yet.
Too much talking, not enough studying. Also, as you point out, it can be read online but not downloaded or printed.
It was just in the regular chat forum. But that’s a good idea, putting it under “Show me the science,” so I moved it! 
My only question is, why didn’t they measure the platelet reactivity before & after administering erythritol to the 8 healthy individuals? Why only measure their blood erythritol levels? The former would have been much more convincing to me.
Instead, they only measured blood erythritol levels & then said "these people must be at increased risk because when we added high amounts of erythritol to blood samples of mice and humans, we saw increased platelet reactivity’
Or maybe I am reading it wrong.
The abstract states that they’ve analysed three studies, involving a total of 4139 people, showing an association between the use of erythritol and other polyols and major cardiovascular problems. They also cite data showing that erythritol does bad things to platelets in vitro and causes blood clots in vivo. The pilot study you mention, with 8 participants, merely shows that when they ate erythritol, the level of erythritol went up to a level shown to be hazardous in the in vitro and in vivo studies.
I thought it might be useful to quote the funding and ethics sections of the paper:
This work is supported by grants from the NIH and Office of Dietary Supplements P01 HL147823, R01 HL103866 (S.L.H.), the Leducq Foundation 17CVD01 (S.L.H. and U.L.) and the Deutsche Forschungsgemeinschaft WI 5229/1-1 (M.W.). A.H. is a participant in the BIH-Charité Advanced Clinician Scientist Program funded by the Charité—Universitätsmedizin Berlin and the Berlin Institute of Health. The LipidCardio Study was partially funded by the Sanofi-Aventis Deutschland GmbH (I.D. and U.L.). P.P.S. was supported in part by an AHA postdoctoral grant 20POST35210937
Hazen reports being named as co-inventor on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics, being a paid consultant formerly for Procter and Gamble and currently with Zehna Therapeutics. He also reports having received research funds from Procter and Gamble, Zehna Therapeutics and Roche Diagnostics, and being eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Cleveland HeartLab, a wholly owned subsidiary of Quest Diagnostics, Procter and Gamble and Zehna therapeutics. Tang reports being a consultant for Sequana Medical A.G., Owkin Inc., Relypsa Inc. and PreCardiac Inc., having received an honorarium from Springer Nature for authorship/editorship and American Board of Internal Medicine for exam writing committee participation—all unrelated to the subject and contents of this paper. The other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
I assume that neither Deutsche Forschungsgemeinschaft, Sanofi-Aventis, nor Procter & Gamble make products containing erythritol, but rather have competing non-sugar sweeteners.
