This article, published in Nature Medicine on February 27th, has drawn a lot of attention. I’m
going to try to explain it simply, without taking a stance. First some background.
Erythritol is a popular artificial sweetener that has become more widely used in recent years due to
its 0 calorie content and low glycemic index. It is called an artificial sweetener because although
our bodies produce small amounts of it, and it’s present in small amounts in fruits and vegetables,
humans have learned to produce it in large amounts artificially. Erythritol has 70% the sweetness
of sugar and doesn’t have a lingering aftertaste like some other sugar substitutes. It also tends
to have less of a laxative effect than other sugar alcohols. Hence, it’s become a popular choice for
weight loss and to improve glycemic control for those struggling with type 2 diabetes. It has been
predicted that erythritol’s market share in the sweetener sector will double in the next 5 years!
The authors of the Nature paper discuss how, while artificial sweeteners are generally
considered safe by the FDA and European Union, there has not been much research into their
long-term health effects with randomized clinical trials examining long-term safety of consumption.
There have been short term animal toxicity studies of erythritol’s safety and reported human clinical
studies with ingestion up to 4 weeks. Early animal diabetes model studies implied that erythritol has
some benefits like antioxidant potential, and a study showed improved endothelial function after
4 weeks of consuming erythritol-containing drinks in patients with diabetes.
These studies, along with the knowledge that the human body produces erythritol naturally on its
own (though admittedly at 1000x lower levels than those found in processed food additives)
are the reason why erythritol was generally recognized as safe by regulatory agencies.
However, other studies have shown that plasma levels of erythritol were associated with 9-month
central adiposity weight gain and that erythritol levels were associated with type 2 diabetes onset.
The authors of this article originally weren’t focused on erythritol. They were trying to
find chemicals in blood that could predict a person’s risk for a major cardiovascular event,
which includes stroke, heart attack, or death. Between 2004 and 2011, they analyzed blood samples
from 1157 people at risk for heart disease. The researchers found that erythritol was
among the molecules that were the highest major cardiovascular event risk predictors. To further
investigate this association, the researchers took blood samples from 2149 people in the US and 833
people in Europe. Among the three sample groups, over half of the people were male and in their 60s
and 70s. Three quarters had coronary disease or high blood pressure. A fifth had diabetes.
This study suggests that, in people with EXISTING risk factors for heart disease, levels of
erythritol circulating in blood are associated with 3-year risk for major cardiovascular events.
After adjustment for cardiovascular risk factors, the study found that being in the top 25% of
erythritol blood levels vs in the bottom 25% was significantly associated with risk
of major cardiovascular events in both the US and European groups, and this applied to
both males and females. Factoring in coronary artery disease did not substantially change the
association of erythritol levels with the incidence of major cardiovascular events.
Since a positive association between circulating erythritol levels and major cardiovascular event
risk had been observed, the authors investigated a potential mechanism behind this association.
They decided to look at erythritol’s impact on platelet function in humans, and in live mouse
models of arterial injury. Platelets are a component of blood that react to bleeding
from an injured blood vessel by clumping together, resulting in clot formation. While blood clots are
important to stop bleeding when you get injured, inappropriately formed blood clots can block blood
flow, and they can break off and travel to the heart, where they can cause a heart attack. If
they travel to the brain, they can cause a stroke. While glucose did not have an effect on platelet
aggregation, erythritol was found to enhance it in samples of platelet-rich plasma from healthy
volunteers. Following exposure to dietary erythritol, the researchers found that it’s
possible that a prolonged period of potentially heightened clotting risk may occur. The
researchers also looked at how erythritol impacted clotting potential in live mice in a carotid
artery injury model. They found that higher levels of circulating erythritol resulted in a higher
rate of clot formation and a decrease in time till blood flow stopped following arterial injury.
Finally, the researchers loo¬ked at what the physiological range in circulating erythritol
levels would be after dietary exposure to foods and beverages containing erythritol. They examined
erythritol plasma levels in 8 healthy participants after they consumed an erythritol-sweetened drink
containing 30 grams. This amount of erythritol is comparable to the amount that would be consumed
by drinking a commercial can of an artificially sweetened beverage or a pint of keto ice cream.
The researchers found that erythritol plasma levels were 1000-fold higher for hours after
ingestion and stayed elevated for over 2 days in all participants. These concentrations were well
above the thresholds of erythritol observed to cause significant increases in platelet function.
Before making any conclusions from this study, remember that the subjects of this
study were people already at risk for major cardiovascular events. And in this group,
the researchers had ONLY established correlation, not causation! Hence,
these results should not be extrapolated to the general population. However, the researchers state
that we need further safety studies to examine the long-term effects of artificial sweeteners, and
erythritol specifically, especially for patients at increased risk of cardiovascular disease.
We need to do more trials with appropriate follow-up duration and establish reporting
requirements, safety profiles and margins of daily intake amount. Especially since
artificial sweeteners are marketed towards patients with diabetes and obesity,
and those with a history of CVD or impaired kidney
function – which is the population already at a heightened risk for major cardiac events.