Mar 02, 2023

Does the Zero Calorie Sweetener Erythritol Cause Cardiovascular Disease? A Review of the Nature Medicine Study

Unless you’re living under a rock, I’m sure by now you’ve heard at least something about the new erythritol study. I am not the biggest consumer of social media content so I often miss the trends on social media but this study has made such a splash that I had three different colleagues contact me separately to talk about it. Couldn’t avoid it if I tried!

The reason why this study has gotten so big is because it has led to sensational headlines such as: Zero-calorie sweetener linked to heart attack and stroke, study finds. This has obviously led to a huge uproar with members of the low carb community calling the study rubbish and everyone else pointing a finger saying, “I told you so!” Even worse is the number of “experts” using this study to suggest that sugar is better than erythritol. Not so fast y'all!

In this article, I’m going to break it all down covering what the study did, what they found, what they concluded, what experts are saying, and my take on the whole thing. Hold on to your butts.

Before we get into the new study, let’s talk briefly about what erythritol is for anyone who doesn’t know.

What is Erythritol?

Erythritol is a sugar alcohol that is naturally occurring in some fruits and fermented foods but is primarily produced commercially through a fermentation process. Erythritol is about 70% as sweet as table sugar but contains almost no calories and has a low glycemic index, which means it does not significantly raise blood sugar levels which is why it is so popular in the low carb/keto world.

While erythritol is most popular in the keto space, its original purpose as a sweetener was for type 2 diabetics and its history actually goes back much further. Erythritol was first discovered in 1848 by Scottish chemist John Stenhouse, who isolated it from the lichen Roccella tinctoria. However, it was not until the 1990s that erythritol began to be produced commercially as a low-calorie sweetener.

The commercial production of erythritol involves the fermentation of glucose or cornstarch with a yeast called Moniliella pollinis. The resulting product is then purified and dried to form a white crystalline powder that is, again, about 70% as sweet as sugar.

Today, erythritol is GRAS certified by the FDA and is widely used as a sugar substitute in a variety of food and beverage products, as well as in dental products like toothpaste and mouthwash. It is approved for use as a food additive by regulatory agencies in the United States, Europe, and many other countries around the world.

While erythritol is most commonly known as sweetener, many don’t know that erythritol is actually produced in the body as well! The human body produces erythritol from glucose via the pentose phosphate pathway and research has shown that production is increased under conditions of elevated oxidative stress. Hold onto that piece of information because it will serve you here in a bit.

Let’s get into the study.

The Study: The artificial sweetener erythritol and cardiovascular disease

The study (1) that everyone is up in arms about was published in Nature Medicine on February 27th, 2023 and is titled: The artificial sweetener erythritol and cardiovascular event risk.

In this study, researchers started by analyzing the blood of nearly 1,200 study participants looking at different compounds that could be linked to cardiovascular disease. In this part of the study they found that erythritol had one of the strongest correlations to cardiovascular disease risk.

The next thing the researchers did was analyze the blood of nearly 3,000 participants from the United States and Europe and found that circulating erythritol levels were higher in individuals with cardiovascular disease. In fact, they found that individuals in the top 25% of blood erythritol levels were 2.5 - 4.5 times more likely to have a cardiovascular event compared to the 25% with the lowest levels. The study even went as far as reporting that with each micromole increase in erythritol levels there was a 16-21% increase in cardiovascular disease risk.

Next, the researchers set out to determine how exactly erythritol could be causing cardiovascular disease. Here they found that high erythritol levels correlated with higher blood clotting risks and thrombosis.

The final part of the study involved the researchers giving 30g of erythritol to 8 subjects and assessing their blood erythritol levels. Here they found that blood erythritol levels increased 1,000 fold compared to baseline and levels remained elevated for days after consumption.

All of this led to the researchers concluding that erythritol is associated with risk of thrombosis and major adverse cardiovascular events.

Is their conclusion valid?

What the Experts are Saying

According to the mainstream media, it is. From CNN to The Washington Post to The New York Times, headlines about the link between the sugar substitute erythritol and heart attacks and strokes have been popping up like pharmaceutical patents when new treatments are discovered (sorry, had to use the opportunity to take a shot at them). Even health information providers that are often considered reputable like the Cleveland Clinic (not sure if I agree) are posting these headlines. Though it’s worth pointing out that despite the headlines, many of the individuals quoted in these articles are giving much more reasonable conclusions like Dr. Stanley Hazen, the co-head of Preventive Cardiology at Cleveland Clinic, who said, “It is important that further safety studies are conducted to examine the long-term effects of artificial sweeteners in general, and erythritol specifically, on risks for heart attack and stroke, particularly in people at higher risk for cardiovascular disease” Nothing wrong with that statement.

There has been no shortage of health experts on social media posting about this study saying that erythritol is dangerous and should be avoided. Some even suggesting that it is better to just eat sugar. All while other experts are saying that the study is bogus, flawed, and there is no reason for concern.

Who’s right?

Our Take on the Study

For starters, I want to say that this is actually a pretty strong study. Despite many people dismissing it because the researchers only used 8 participants in the final part of the study, I actually think it was conducted very well because the researchers did what they are supposed to do.

In this study, the researchers started with epidemiology to find correlations that they could then investigate further. Instead of just publishing those correlations without further investigation, like researchers have done so many times for topics like meat and cholesterol, they actually went a step further and investigated in real humans. Yes, the sample size was small but this is typical for an initial trial. Studies are expensive so smaller trials are needed to determine whether or not there is enough evidence to warrant a larger study. The researchers did a great job of pointing this out in their conclusion where they simply say that erythritol is, “associated with” these cardiovascular events and that “studies assessing the long-term safety of erythritol are warranted.” A very proper and mature conclusion based on what the study found.

So my problem isn’t with the study. My problem is with the mainstream media’s interpretation of it. Here is a great take from Mike Mutzel of High Intensity Health:

The first thing to come back to here is the fact that the body produces erythritol naturally. Thus, when we look at the blood samples in this study, we have to understand that this isn’t blood levels of erythritol being elevated because of erythritol consumption, but rather from endogenous erythritol production.

This is important because there is a certain sub population of people that produce more erythritol naturally….individuals with obesity and poor metabolic health. The reason this matters is because we should actually expect individuals who are more likely to have cardiovascular disease to have higher erythritol levels. But that doesn’t mean the erythritol levels caused the cardiovascular disease.

This is a similar narrative to what we have historically seen in research on cholesterol/LDL and cardiovascular disease risk. Individuals with poor cardiovascular health typically have higher LDL levels but as research has now pointed out, this doesn’t mean LDL is the cause (2). Even though we have jumped to that conclusion and stayed there for several decades.

What we are seeing in this study is misinterpretation of positive correlation. Positive correlation is when two variables in a data set are related so that when one is elevated so is the other and vice versa. In this case, we are seeing that when erythritol is high so is the risk of cardiovascular disease. But this is where the increasingly popular adage, “correlation does not equal causation” comes in. Just because there is a correlation does not mean we can automatically infer cause and effect.

Still, the researchers did a great job of attempting to identify how erythritol could be related to cardiovascular disease and isolated that the mechanism is through blood clots and thrombosis so we aren’t out of the woods yet. Let’s look at that part of the story.

How Erythritol Could Cause Heart Attacks and Strokes

This is where things get a little more interesting. Like many others businesses, BioCoach has been leveraging new A.I. tools like ChatGPT to help scale some of our marketing efforts. To help me aggregate some information, I asked Chat GPT to come back with a breakdown on the mechanisms behind erythritol causing blood clots and thrombosis. This is what it came back with:

“I'm sorry, but it is not accurate to state that erythritol causes blood clots and thrombosis. Erythritol is actually considered to have antithrombotic properties, meaning it can help prevent blood clots from forming. This is because erythritol has been shown to inhibit platelet aggregation, which is an important step in the formation of blood clots. In fact, some studies have suggested that erythritol may have potential therapeutic applications in preventing thrombosis in certain conditions, such as heart disease and stroke. However, it is important to note that more research is needed to fully understand the effects of erythritol on blood clotting and thrombosis.”

In case you aren’t familiar with what ChatGPT does, it scours the internet, including research to give itself a knowledge base to help answer the questions and requests it is given. I have used ChatGPT quite a bit and often on topics where I am very familiar with the science, like keto, and 99% percent of the time it comes back with very accurate information.

Regardless, I treated this response with skepticism and decided to continue digging. Turns out if you dig deep enough you do find some potential mechanisms where erythritol could contribute to heart disease risk such as this study that found erythritol can make our platelets “stickier” pointed out by Harvard data scientist and MD/PhD Adrian Soto-Mota.

How can ⬆️erythritol cause ⬆️🧠🫀 infarctions?

How can we address the possibility of the ⬆️CVDrisk mileu raising ⬆️🩸[erythritol] instead?

Study 3: Platelet studies.

Does erythritol make your platelets "stickier"?

Yeah, it looks like it does. pic.twitter.com/phb0OSliOP
— Adrian Soto-Mota (@AdrianSotoMota) March 1, 2023

As you keep digging, you see a lot of compelling information for platelet aggregation from high erythritol levels which is why these researchers came to the conclusion that there was indeed a mechanism at play that could explain the higher risk of cardiovascular disease when plasma erythritol levels are high.

However, there is a little more to that story. As Robb Wolf did a great job pointing out in his newsletter, research has also shown that normal glucose levels do not pose the same risk of platelet aggregation and blood clotting (3). This is something this study did not account for. In general, they did not account for the difference between metabolically healthy and unhealthy individuals and from the research I have read so far, this may make all the difference.

Should I Cut Out Erythritol?

This should be your next logical question. What does it mean? Does it mean I should keep eating erythritol or cut it out? To answer this, let's return to the last part of the study.

If you recall, the last part of the study involved giving 8 participants 30g of erythritol and found that this led to a 1,000 fold increase in plasma erythritol levels and those levels remained elevated even two days after consumption. Since the increase was considered to be beyond the threshold associated with “platelet reactivity and thrombosis potential”, the researchers concluded that the consumption of erythritol was leading to an increase in risk factors of clot formation.

Now you may be thinking, “30g is a lot. Sounds like those studies that say that aspartame is bad but are giving it in higher doses then any human would consume.” Not so fast.

If we look at common “keto-friendly” foods, in particular ice cream, we find that a full pint contains exactly 30g of erythritol. Of course, we likely shouldn’t be eating a full pint of keto ice cream but by a show of hands, who here has done that?

Despite this, we still have to consider how accurate the threshold is that the researchers are using to determine whether or not erythritol is thrombotic. Plus, we have to consider how that changes when someone has healthy plasma glucose and insulin levels. None of which has really been evaluated in the research.

Another aspect we have to consider is the research out there that actually shows erythritol could be cardioprotective (4)(5). That’s right, that research does exist. Dr. Ryan Lowery did a great job highlighting some of it in his response to this study:

That clears it up right?! LOL, probably not. If anything, it makes it more confusing. One side of the story is saying erythritol causes cardiovascular disease and the other says it prevents it. What are we supposed to think?

You should think what most sensible people have thought. We need more research. To really understand what is going on here, we need to continue studying erythritol and study it in larger clinical trials with more health diverse populations to understand how different factors can influence erythritol’s action. Maybe the poison is in the dose. Maybe the poison is dependent on your metabolic health. Maybe the poison is based on what the rest of your diet looks like. Maybe there is no poison.

To answer your original question,”should I cut out erythritol?”, my answer is nah. I haven’t seen anything here that makes me concerned about moderate erythritol consumption. Especially in the context of a low carb/low processed food diet where blood sugar, insulin, and inflammation levels are in check. Plus, I’ve seen too many people dramatically improve their metabolic health and reduce cardiovascular disease risk factors on a low carb diet while consuming erythritol. I do, however, think that it is warranted to be mindful of how much we are consuming. If there is any truth in this study, it would tell us that consuming too much erythritol in a single setting and too frequently, could be the real cause for concern.

Conclusion

To wrap it up, the story is the same as it usually is. It depends and don’t believe everything media headlines tell you. The evidence that erythritol is dangerous just isn’t there right now so there is no reason to freak out and denounce your keto diet.

It’s worth pointing out that I have had many individuals respond to my posts on social media saying things like, “just eat whole foods and don’t worry about it”.

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A post shared by Chris Irvin (@theketologist)

While I totally agree that this is the best approach, I think we need to be mindful of the fact that different people are at different stages of their health journey. For some, a sugar alternative like erythritol could be what allows them to take the first step towards better health. The majority of our population is addicted to sugar and if something like erythritol is going to help more people get off of sugar, then you are looking at a net positive. Regardless of what those health “experts” are telling you.

Despite all of that, if you are still concerned you can always opt for other low calorie sweeteners like stevia or monk fruit.

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