There was a paper that recently got published in the British Medical Journal (BMJ) looking at a sweetener called xylitol and its potential to cause cardiovascular disease.
This is a study published by the same lab using very similar techniques and very similar methods with xylitol.
The first thing to point out is that they were not measuring xylitol intake. Now, what's xylitol? Xylitol is a sweetener that basically has a one-to-one sweetness to glucose, so it's used as a sweetener in many keto-friendly and low-carb products because it doesn't impact blood glucose nearly as much as regular sugar. It still has calories and slightly raises blood glucose but not to the same extent as regular sugar. So, it is a good sweetener to use for people who want to keep their postprandial blood glucose down. I question how important that is, as we've talked about before, but that's neither here nor there. The nice thing about xylitol is that, unlike things like sucralose, which is 600 times sweeter than sugar, you don't need very much of it, so you have to add bulking agents to it, and it just doesn't have the same consistency as sugar. Xylitol is one-to-one the same sweetness as sugar, so you can use it in any recipe that calls for sugar.
In this study, they were looking at the incidence of major cardiovascular events (MACE) and its association with xylitol levels in the blood. They did what's called a metabolomics panel, where they ran a bunch of different metabolites in the blood and looked at whether they had any association with the incidence of major cardiovascular disease events.
Why is that important? Well, it's important because we're not talking about people who are taking in xylitol. They didn't measure their xylitol intake or anything like that. Your body naturally produces xylose, which is converted to xylitol as part of the metabolic process. So, they showed these people had higher levels of xylitol, but they were not measuring their xylitol intake.
I also want to point out that the cohort they used were very, very sick people. We're talking about people with an average age of 64, over 20% had diabetes, over 70% had hypertension, over 75% had a history of cardiovascular disease, over 75% had a history of coronary artery disease, almost half had a history of a heart attack (myocardial infarction), almost 20% had a history of heart failure, over 70% were using ACE inhibitors, which are prescribed to patients at risk for heart attacks, and half of them were taking aspirin to thin their blood to lower their risk of having a heart attack. So, we're talking about a very, very sick cohort.
They did the metabolomics assessment. What did they find in terms of association? They found about an 80% risk increase in people who had higher levels of xylitol in their blood compared to those who had lower levels. There are different ways to do statistics when it comes to associations. When they used xylitol in the blood as a continuous variable and adjusted for levels of CRP (a marker of inflammation) and other traditional cardiovascular disease risk factors, the risk increase went down to 6% per standard deviation of xylitol. That's a lot different from 80%, okay? It still remains statistically significant. When we're talking about relative risk, it's important to understand that it sounds more alarming than it is. If a population has a 10% absolute risk of something, and that risk is increased by 80%, it means the risk goes from 10% to 18%, not from 10% to 90%.
Now, a 6% risk increase would be the difference between going from 10% to 10.6% absolute risk. It sounds sexy in the news, but it's not nearly as significant in terms of absolute numbers. You don't want to do things that drastically raise your risk. For reference, something like regular smoking raises your risk of cancer and cardiovascular disease by 300-900%, depending on dosage and type.
There is an association between not xylitol intake but the levels of xylitol in the blood and the risk of major cardiovascular disease events. Once they controlled for confounding variables, it wasn't nearly as alarming as reported. They also gave subjects a 30g dose of xylitol, comparable to some keto ice creams that use xylitol. They found that postprandially, it increased xylitol levels by a thousandfold. This sounds scary, but xylitol is cleared out of the bloodstream very quickly. Its half-life is a couple of hours, and after 24 hours, there is no detectable xylitol in the urine.
Here's the important point: when they did these metabolomics, they were not measuring xylitol intake. People with higher blood levels of xylitol might not have high intake, because xylitol is back to baseline after an overnight fast. High levels of xylitol are more reflective of endogenous metabolism. If you're healthy, you metabolize it quickly. If you're unhealthy, with high blood pressure or metabolic syndrome, your metabolism is dysregulated, causing higher levels of these sugar alcohols in your blood. This is likely reverse causation.
The study also looked at platelet aggregation and thrombosis, important factors in cardiovascular events. They found that xylitol significantly accelerated platelet aggregation and thrombosis in a model using mice predisposed to have carotid injuries. They also saw increased platelet aggregation in humans after xylitol intake. However, this was done in a lab setting and may not reflect real-life scenarios.
So, what's the takeaway? If you have a risk of cardiovascular disease, maybe you should avoid xylitol if it does indeed induce platelet aggregation. But based on this study, I'm not sure it does. The study shows association but likely reverse causation. No studies show that xylitol intake is a risk factor for cardiovascular disease. If you're healthy, xylitol is metabolized quickly.
I'm not saying you should take xylitol, but I'm not ready to freak out over this study. If it helps you control your overall calorie intake, it can be a useful tool. But the study measured blood levels, not intake, so it's just as likely reverse causation.