A disturbing study had sparked more confusion about the potential ill-health effects of consuming one of the most common artificial sweeteners.

The study – a combined effort by Sweden’s Karolinska Institute in Stockholm and Chinese colleagues – looked at the effect on mice of aspartame – an artificial sweetener commonly used in diet soft drinks and baked goods.

The research, published in the Cell Press journal Cell Metabolism on Wednesday, found that aspartame triggers increased insulin levels in animals. In turn, that contributed to atherosclerosis– buildup of fatty plaque in the arteries, which can lead to higher levels of inflammation and an increased risk of heart attacks and stroke over time.

The research was inspired by a can of diet soft drink during a project meeting.

“One of my students was sipping on this sugar-free drink, and I said, ‘Why don’t you look into that?’,” senior author Yihai Cao, from Stockholm’s Karolinska Institute, said.

The researchers fed mice daily doses of food containing 0.15 per cent aspartame for 12 weeks – an amount equivalent to a person drinking about three cans of soft drink a day.

Aspartame-fed mice developed larger and more fatty plaques in their arteries and exhibited higher levels of inflammation. Both are are hallmarks of compromised cardiovascular health.

When the team analysed the mice’s blood, they found a surge in insulin levels after aspartame entered their system. The aspartame, which is 200 times sweeter than sugar, seemed to trick the receptors into releasing more insulin.

They then demonstrated that the mice’s elevated insulin levels fuelled growth of fatty plaques in the mice’s arteries, suggesting that insulin may be a link between aspartame and cardiovascular health.

Next, they investigated how exactly elevated insulin levels led to arterial plaque buildup and identified an immune signal called CX3CL1, which was especially active under insulin stimulation.

“Because blood flow through the artery is strong and robust, most chemicals would be quickly washed away as the heart pumps,” Cao said. “Surprisingly, not CX3CL1. It stays glued to the surface of the inner lining of blood vessels. There, it acts like a bait, catching immune cells as they pass by.”

Cao and his team plan to try to repeat the findings in humans. Cao also predicts CX3CL1 could be a potential target for chronic conditions beyond cardiovascular disease, given that blood vessel inflammation is involved in stroke, arthritis, and diabetes.

“Artificial sweeteners have penetrated almost all kinds of food, so we have to know the long-term health impact,” he said.

However, some Australian experts were sceptical about the findings.

“The authors would appear to think little work has been done on safety testing in aspartame; this is just not true,” RMIT University chemistry professor Oliver Jones said.

“Aspartame is one of the most researched ingredients in the world. It is just that a lot of the data is in safety assessments for regulatory approval, not the academic literature.”

He said even if aspartame had caused an increase in cardiovascular risk, “then that risk would likely be very small compared to things like high-fat/high-sugar diets and lack of exercise”.

“In short, I don’t think this study itself gives us more reason to worry about diet drinks or aspartame,” Jones said.

Dr Ian Musgrave, from the University of Adelaide, said the potential health effects of artificial sweeteners were controversial. However, the genetically-engineered mice in the study were unlikely to replicate the biology and dietary situation of most humans.

“Importantly, in the blood vessel experiments, the effects of an equivalently sweet dose of sugar was not studied, nor the effect of the reduction in calorie intake by the amount of aspartame consumed,” Musgrave said.

“While the study may have given us a new target for treating plaque build-up in one of the body’s inflammatory molecules, it does not suggest people should give up their artificially sweetened drinks.”

However, Dr Yutang Wang from Federation University Australia, was more cautious.

“Artificial sweeteners are often considered a healthier alternative to sugar and are commonly found in a variety of foods and drinks, including soft drinks, baked goods, and frozen desserts,” he said.

“Many people turn to these sugar substitutes to cut down on calories, avoid blood sugar spikes, or prevent tooth decay … This new research provides compelling evidence that these sweeteners directly cause cardiovascular disease.”

Wang acknowledged the study’s limitations, but warned it might be time to reconsider consuming artificially sweetened products.

“Reducing their intake could be a simple yet powerful step to protect ourselves from heart attacks and strokes,” he said.

Professor Mark Wahlqvist, the former head of medicine at Monash University and and a past president of the International Union of Nutritional Sciences, agreed. He said the finding that aspartame can adversely affect arterial health was disturbing.

“Evidence that [aspartame’s] substitution for sugar in the prevention and management of obesity has been unconvincing, as for similar substitutions,” said.

“We should stop the inappropriate use of sugar substitutes.”