Erythritol, and the More Artful Avoidance of Excess Sugar

Erythritol is commonly used as a sugar substitute.

Readers of this column (thank you!) have no doubt encountered the extensive media coverage of a recent study implicating an artificial sweetener- erythritol- in potential crimes against our vasculature (i.e., increased risk of “MACE,” or major adverse cardiovascular events: heart attack, stroke, and cardiovascular death). Those paying attention to the prevailing media patterns in general, and nutrition coverage in particular, have good cause to ask: does the study of a compound the FDA regards as generally safe really warrant all this drama? 

The question is always justified, because the media mantra is - whether confessed or concealed by a given source - “comfort the afflicted, afflict the comfortable.” If you are comfortably convinced that sugar alcohols are safe, it’s time to afflict you with doubt. As for nutrition coverage, it is notoriously skewed toward the contrarian and dramatic. If 9,999 studies all reach the same conclusion and one diverges, then the one- no matter how dubious- gets all the headlines.

So, a deep breath and a moment of reflection were certainly warranted when the allegations against erythritol were levied. But in this case, the comprehensive elegance of the study does seem to support the charges, and the media attention to them.

The study, published in the prestigious Nature Medicine, played out in four interrelated parts. First, the team conducted what they call a “metabolomics discovery” phase: they examined blood samples in over a thousand patients undergoing cardiac assessment, looking for associations. In this phase, which might reasonably be considered a fishing expedition (i.e., they weren’t looking for anything in particular, they were just looking to see what they would find), they found a surprisingly strong and dose-responsive association between erythritol levels in the blood and MACE.

They took this information with them into two distinct “validation” cohorts, one of over 2,000 adults in the U.S., another of nearly one thousand in Europe, both undergoing cardiac evaluation. This time, they were testing the established hypothesis that cardiac events would correlate with blood levels of erythritol- and they did, again with considerable statistical strength, and again in a dose-responsive fashion.

This sequence is important, because an initial exploration of data will naturally elevate the strongest associations, no matter their validity. The risk of a statistically robust “fluke” is high, in other words. The follow-up validation tests, however, are no longer random explorations of data; they are targeted, testing the specific hypothesis that the association found initially at random will now recur because it is physiologically meaningful. Erythritol passed through both filters.

The investigators then went looking for mechanism, testing erythritol in cell culture and in mice. They found that it markedly increased the tendency of human platelets to stick together- a hallmark of cardiovascular events- and accelerated blood clot formation in mice. Collectively, the study components thus far suggest both that high levels of erythritol in blood predict high risk of MACE, and that the association makes clear, mechanistic sense.

Finally, the researchers tested the effects of erythritol intake on blood levels in a small group of healthy, human volunteers. They found that levels of the sweetener used commonly in food products (notably, a wide array of recently introduced products designed expressly to help people have their ketogenic diet and feed their sweet tooth, too) resulted in rapid, extreme surges in blood levels (i.e., a thousand-fold increase) with marked elevations persisting for more than two days.

This is not quite the definitive evidence of cause-and-effect that a randomized, intervention trial with erythritol would be, in which those getting erythritol had more cardiac events than those getting matched placebo. The authors note this themselves, saying only that the association warrants such study (of note: the ethics of an intervention study in the aftermath of this paper are suspect; would you like to be randomly assigned to high-dose erythritol?). But the compilation of findings here is a compelling tale of caution at the very least. The findings were consistent, strong, and robust across a wide array of statistical adjustments. Of note, however, the researchers were not able to adjust for overall diet quality; if reliance on a sugar substitute tracks generally with more highly processed foods and lower diet quality, some, or conceivably all, of the adverse influence observed here might be due to factors other than direct effects of erythritol. (There are, in other words, other fish of concern in the metabolomic sea.)

That is conjecture, and in the meantime, you have a choice to make: do you consume products with erythritol, or avoid them? The precautionary principle argues clearly for the latter, and for what it’s worth- I have been unenthusiastic about so-called “artificial sweeteners” all along, and personally avoid them entirely. There have, in my view, long been reasons to be wary, and there is- in my view- a much better way to minimize your sugar intake. Back to that momentarily, but first, a quick word about erythritol.

The compound is a sugar alcohol (among the exclusions on a low FODMAPs diet), essentially a fermented derivative of naturally occurring sugars. There is low-level fermentation of fructose in fruits, and thus, very low levels of naturally occurring erythritol there. Some forms naturally in the human body for related reasons. But levels used in commercial foods are typically a thousand-fold more concentrated, essentially delivering a pharmacologic dose never seen in Nature. As Paracelsus warned, “the dose makes the poison.” In the case of erythritol, it is its concentration that is genuinely “artificial,” not its composition.

What is the basis for my long-standing misgivings about artificial sweeteners?* 

My original concern was simply that our innate predilection for sweet (a.k.a, a “sweet tooth”), known to be willfully exploited by food manufacturers, is exactly that: a “sweet” tooth, not a “sugar” tooth. In other words, any compound that registered as “sweet” in the brain would propagate the same cravings for ever-more-sweet as seen with sugar. There is some evidence that artificial sweeteners do this.

There is also a relative lack of evidence that artificial sweeteners confer the intended benefits, namely reducing total sugar and calorie intake, and facilitating weight control and metabolic health. Some short-term studies suggest that such products as diet sodas do help with reductions in calories, total sugar, and weight management - but other studies suggest they do not. The sugar and calories displaced from one part of the diet exploit the unaddressed sweet tooth to sneak back in elsewhere.

Recent studies have gone further, implicating at least some artificial sweeteners in disruption of the microbiome, and the propagation of resistance to insulin- among the very liabilities they are intended to obviate. Stated bluntly, via harm to our resident bacteria, these contrived chemicals may break the very metabolic pathways they are touted to fix.

We might append as a closing argument that the indictments against ultraprocessed foods are piling up fast; such foods are directly implicated in everything from weight gain and obesity, to all-cause mortality.  Artificial sweeteners show up in such foods, and as noted above, may be one among the causes of their harms, or may just be along for the ride. Either way, the case for eating real food, rather than ingestible junk masquerading as food, is strong.

First, there is a great deal of “stealth sugar” in the typical, modern diet – sugar added to foods by manufacturers as a goad to appetite, often foods not even recognized as sweet. This includes everything from salad dressings and pasta sauces, to salty snacks. Yes, where Frankenfoods roam, even your French Fries and potato chips are a source of added sugar.

This matters for two reasons: (1) sugar in diverse foods increases total daily intake, and it is the dose that matters; and (2) the addictive nature of sugar includes “tolerance,” meaning the more you get, the more you need to feel satisfied (a cardinal feature of all addiction). The unrecognized stealth sugar consumed every day drives up the threshold for satisfaction from foods and drinks that you do register as sweet, thus increasing total daily intake even more. A grim, positive feedback loop ensues, in which a sweet tooth is generously fed into a sweet fang, that hangs menacingly over your every dietary choice.

Fortunately, this can all be reverse-engineered by cutting out stealth sugar. No one needs marinara sauce or salty snacks with added sugar- so read food labels, and avoid it. Yes, choosing products free of added sugar means more work at the grocery store at first; but not for long. Once you’ve identified those preferable products at comparable price points and established that you and your family are just as happy with them- just keep buying them instead. This small, brief investment of effort yields large, lasting returns- because you can cut out gram after gram of daily sugar intake this way, without yet having even touched the foods where sweetness actually matters.

Those come next, and it’s easier than you think (really; I’ve been through this with countless patients over a span of 30 years or so). 

What tastes ‘good’ is whatever our brains tell us tastes good; there is no ‘universal good’ or ‘universal bad’ taste chemical. The only evidence we need of this is the beautiful variety of cultural diets, featuring florid variation in every taste category from sweet and salty, to spicy and umami.

Perception is reality, and taste is mostly learned perception. There are, simply, many chemical compounds that stimulate receptors on our tongues (and in our nasal passages), that convey electrical messages to our brains. Our brains then decide “good,” or “bad,” based ever so slightly on the innate orientation of our DNA (and the urgencies of evolutionary biology), and to a much greater degree- on our personal history. The single greatest, and most malleable determinant of taste preference is…familiarity. Taste buds are adaptable little fellas, and readily learn to love the foods they’re with.

That’s why, if you eat like most people in the modern world, you have a taste for junk where food ought to be. You’ve had decades of habituation to such junk (marketed with gusto to you, and especially, your children), and the egregious surfeit of sugar, salt, all the wrong fats, and chemicals it ushers down your gullet. But taste bud adaptation works just as well in the other direction; incremental improvements in food choice and diet quality reliably translate cravings to aversions, aversions to cravings. Junk can start to taste like junk; food, like food. Your brain’s assessment of what tastes “good” can undergo a 180; and with it, your health, your weight, and much of what ails you.

I have long labeled this process “taste bud rehab,” and it is highly effective and as best I can tell, universal. Trade up your food choices with a bit of patience, and you can come to prefer and love the foods that love you back. The culmination of this process is an abiding preference for real, unadulterated food, mostly plants (the “not too much” tends to take care of itself, because whereas ultraprocessed foods sabotage satiety by design, among the many virtues of wholesome foods direct from Nature is their capacity to fill us up on far fewer calories)- and a very high quality diet. There is a place in this dietary pattern for sugar, but it is a very small place.  Put sugar in its limited place in a healthful diet to derive maximal pleasure from its minimal dose. There is no place, nor need, for artificial sweeteners.

Summing up, the best-case scenario for erythritol- and by extension, other sugar substitutes- is that they are not, in fact, directly responsible for the various ills with which they are associated. The worst-case scenario is that they are directly and entirely responsible. Nowhere in that range is there even the remote possibility that these compounds are in any way directly “good” for us. Perhaps our dietary aspirations should aim higher than “possible avoidance of overt harm”? Food should actually nourish us. We can titrate down our sugar intake, and dial up our diet quality, in ways that honor this basic principle.

Efforts to improve diet and health one nutrient or ingredient at a time are, inevitably, prone to the law of unintended consequences. Reducing saturated fat? Beware its replacement with trans fat. Reducing all fat? Beware its replacement with sugar and salt, to say nothing of tossing out the baby (i.e., healthful fats) with the bathwater. Replacing sugar? Beware the introduction of chemical compounds that - probably- damage the microbiome, injure blood vessels, potentially propagate a sweet tooth, and displace calories temporarily without favorably affecting satiety or longer-term energy balance.

The alternative, of course, is the converse: address any given nutrient or ingredient of concern by improving the pattern and quality of your overall diet. This, too, has potentially unintended effects- all favorable. Seeking to lower your blood pressure by reducing sodium intake? Achieve that by eating fewer ultraprocessed foods and more foods direct from Nature, and you will succeed- while also improving your blood lipids, blood sugar, cardiometabolic health, brain health, and so on. So, too, for any other such nutrient adjustment.

The more artful avoidance of excess sugar is achieved not by hoping for the harmlessness of any given chemical compound contrived as its substitute, but by looking past a single ingredient and its potential alternates, to the overall pattern and quality of your diet. Let taste bud rehab work its magic, and come to love the very foods that love your health back. Let a rising tide of overall diet quality lift every boat, and deal not merely with erythritol- but with anything else metabolomic fishing happens to haul in next time.

-fin

*Note: my misgivings about sugar substitutes have not been uncompromising opposition. Whatever the harms of sugar substitutes, they may be less than the harms of the copious sugar they are meant to replace. Accordingly, and at least, they might play a useful transitional role, as in swapping diet soda for regular, before moving on to unsweetened teas, seltzers, or that time honored remedy for thirst: water.

Dr. David L. Katz is a board-certified specialist in Preventive Medicine/Public Health, past president of the American College of Lifestyle Medicine, and the founder and CEO of Diet ID, Inc.