Trouble with Erythritol

I wrote a few months ago about a surprising finding with some food sweeteners. Sucralose and saccharin (but not aspartame or stevia) seemed to bring on impaired glucose tolerance, which is not something that you would have expected from molecules with none of sugar’s metabolic and nutritional effects. That was certainly worth thinking about, but now there are more disturbing results to add to it.

This new paper reports that another widely used non-nutritional sweetener (erythritol) appears to be associated with cardiovascular problems. That’s quite a surprise, because erythritol itself has been considered very safe indeed. It’s been used for decades as a sweetener, and is approved for that use in over sixty countries. To the tongue, it’s about 60% as sweet as sucrose (table sugar), which makes it easier to substitute than some of the far-sweeter alternatives, which then need to be bulked up to keep recipes from being thrown off (and those fillers themselves often cause the recipes to be adjusted). But it has basically no caloric value for the human diet.

Chemically, it’s part of a group of “sugar alcohols”, open-chain polyhydroxy compounds that can be thought of as reduced forms of the simple sugars (where their aldehyde or ketone groups have been taken down to yet another OH group). Erythritol, which is (2R, 3S) 1,2,3,4-tetrahydroxybutane is in fact produced in small amounts in normal human metabolism, and is found naturally in some fruits and other foods. It’s make industrially by breaking down corn starch to glucose and then using fermentation with engineered yeast stains to convert that to erythritol.

But unlike sugars like glucose, we humans have no metabolic pathways that really use erythritol, so when it’s consumed in food it gets taken up almost entirely in the small intestine and excreted unchanged in the urine. This lack of metabolism is another reason it’s been considered safe and more or less biologically inert. It’s not even used by most species of bacteria, which has led to erythritol being a preferred sweetener in things like sugar-free gum, since it’s not associated with tooth decay. The only strike against the sugar alcohols in general (you also see sorbitol and others in foods) has been gastrointestinal upset and diarrhea if larger quantities are consumed. You can see vivid and heartfelt accounts of this on product review sites from people who have consumed too many sugar-free candies in once sitting.

Now, there have been studies that showed that erythritol is apparently toxic to fruit flies. Drosophila seem to like it quite well (they’re very attracted to sweet fermentation products), but it impaired their flight and reduced their lifespan. That last effect may have partly been due to starvation, honestly, and it is also believed to cause osmotic imbalance in them. But nothing like that had ever been seen with humans; it has no such effects even in honeybees.

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.

That’s bad news, and it had never been suspected until now, Platelets are of course key players in blood clot formation, and that activity is normally held in check until there’s been some sort of bleeding injury. Increasing the chances of blood clot formation is the most direct route you can imagine for increasing the risks of stroke and cardiac events through blocking blood vessels - if your clotting behavior is normal to start with, you really, really, do not want to go around activating your platelets. That seems to be a risk under normal erythritol consumption, as determined by separate blood level measurements:

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

No, that’s not good. I would expect these results to set off a flurry of clinical and regulatory interest, and if this holds up I would certainly expect to see it removed from the market. And to be honest, since erythritol is not exactly an essential part of the human diet, 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.

from Hacker News https://ift.tt/el8LY15