Sweeteners Linked to Blood Vessel Inflammation, But Experts Urge Caution
The new mouse study suggests a link between aspartame consumption, insulin levels and blood vessel inflammation.
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Diet sodas and other zero-sugar alternatives owe their sweet taste to artificial sweeteners, such as aspartame.
While these drinks are often positioned as the health-conscious option, some studies have suggested that artificial sweetener consumption may be a potential risk factor for cardiovascular disease (CVD). However, the molecular mechanisms underpinning artificial sweeteners’ association with CVD have remained unclear.
A new animal study suggests that ingesting aspartame causes an insulin spike in mice which can induce or exacerbate atherosclerosis — a build-up of fatty plaque in the arteries. This in turn can lead to higher levels of blood vessel inflammation and an increased risk of heart attack or stroke. The research was published in Cell Metabolism.
Aspartame tricks mice into releasing more insulin
Over a period of 12 weeks, the researchers administered ApoE-/-mice with aspartame orally using a dropper and a solution of 0.15% aspartame in water. At the end of the study period, mice that were given aspartame had developed larger and more fatty plaques in their arteries compared to control mice. The aspartame-fed mice also appeared to exhibit higher levels of blood vessel inflammation, which is another measure of poor cardiovascular health.
Blood analysis revealed that the aspartame consumption had resulted in a large spike in the animals’ insulin levels which may have altered insulin sensitivity.
As a rodent’s response to aspartame might differ significantly from other types of animals, the researchers repeated this feeding study with Cynomolgus monkeys. Again, the consumption of aspartame was found to correlate with a temporary spike in insulin secretion.
To investigate this response, the researchers isolated primary aorta endothelial cells from wild-type C57BL/6J mice and stimulated them with insulin in vitro for 8 hours. Whole-genome expression profiling by mRNA-sequencing revealed that the chemokine CX3CL was upregulated in the insulin-stimulated endothelial cells. When the researchers specifically deleted the Cx3cr1 gene from their C57BL/6J mice, they saw that plaque build-up ceased to occur after aspartame feeding.
These results point to CX3CL1’s role in aspartame’s effects on the arteries, the researchers say. They believe that this could then become a potential therapeutic target for cardiovascular disease and other conditions where blood vessel inflammation is seen, such as stroke and diabetes.
What does this mean for your health?
On the face of things, these results may seem rather scary. However, it is important to take a look at these findings in context.
Several recent reviews and meta-analyses of studies conducted in humans suggest that ingesting aspartame has no significant effects on cholesterol, blood glucose levels or insulin levels.
“This seems like worrying findings but of course, before it can taken seriously, the findings have to be replicated in man,” said Naveed Sattar, PhD, a professor of cardiometabolic medicine at the University of Glasgow, in a statement to the Science Media Centre (SMC). “There is no good evidence from trials that exogenous insulin increases cardiovascular risks in people with prior cardiovascular disease and in people with type 1 [diabetes], by improving glucose levels, exogenous insulin lowers many risks.”
“For now, I remain happy to take sweeteners and related diet beverages instead of sugar-filled drinks, as the former limits excess calorie intake,” Sattar said.
Oliver Jones, PhD, a professor of chemistry at RMIT University also expressed his reservations about the study design in comments to the SMC.
“The main one is that the authors used a particular type of lab mouse called an ApoE mouse, which is bred to be prone to heart disease. They also fed it a high-fat, high-cholesterol diet, which itself increases the risk of heart disease,” Jones said.
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“To my mind, the authors’ admission that feeding mice that are already genetically susceptible to heart disease with a high-fat, high-cholesterol diet that is known to cause heart disease ‘diminishes clinical relevance’ is somewhat of an understatement.”
“They also don’t seem to have measured how much of the aspartame water the mice drank, or the aspartame level in the blood, so it is unknown what the mice actually received,” Jones added.
In addition to its study in academic literature, aspartame has also been subject to extensive analysis from regulatory bodies as part of the need to receive approval before a compound can be used as a food additive.
The US Food and Drug Administration claims that aspartame is “one of the most studied food additives in the human food supply,” having first issued approval for its use in 1974. In Europe, aspartame was fully re-evaluated and approved by the European Food Safety Authority in 2013, with re-evaluations of two related additives — the salt of aspartame-acesulfame (E 962) and neotame (E 961) — currently underway.
“In short, I don’t think this study itself gives us more reason to worry about diet drinks or aspartame,” Jones concluded.
Reference: Wu W, Sui W, Chen S, et al. Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation. Cell Metab. 2025. doi: 10.1016/j.cmet.2025.01.006
