The suspected health harms of artificial sweeteners are piling up – and now a new study has linked one kind of sugar substitute to higher risks of heart health problems.

Physician-scientist Stanley Hazen and colleagues at the Cleveland Clinic's Lerner Research Institute wanted to see if they could find any signs that could warn people they were at greater risk of heart attack and stroke.

They found it in blood levels of organic compounds used as sweeteners, specifically erythritol; a sweetener commonly used in low sugar, sugar-free, and no-carb foods.

Among a group of 1,157 patients undergoing tests at a cardiovascular clinic, those with the highest levels of these compounds in their blood had twice the risk of dying from or experiencing a major cardiovascular event in the three years that followed.

To be clear, the study didn't show that erythritol was coming from artificial sweeteners, or that it was directly causing any of the cardiovascular issues.

And some nutritional scientists not involved in the research have been critical of the study, saying its lab experiments are "unrealistic" and its observational findings are limited because they didn't account for how erythritol can be produced in the body.

But the researchers say their findings are enough to warrant additional investigation.

"Our findings suggest the need for further safety studies examining the long-term effects of artificial sweeteners in general, and erythritol specifically, on risks for heart attack and stroke, particularly in patients at higher risk for CVD," the researchers write in their published paper.

Artificial sweeteners are thought to be chemically inert, but scientists are finding these low-calorie compounds are not necessarily free from health consequences.

While naturally present in very small amounts in fruit and vegetables, levels of sweeteners like erythritol can be 1,000-fold higher in processed foods.

Research shows artificial sweeteners can muck with the microbes in our gut in a way that leads to weight gain and diabetes, and may increase the risk of developing cancer.

Part of the problem is that while artificial sweeteners have fewer calories than the sugars they are replacing – and that may help some people cut down their intake – they taste sweeter and encourage our bodies to want even more of the sugary taste.

"There is an ongoing discussion of the safety of sweeteners – partly because some studies show an increased risk for chronic diseases among those who consume sweeteners, especially in soft drinks," explains Gunter Kuhnle, a professor of nutrition and food science at the University of Reading in the UK.

This new study found a link between levels of erythritol in the blood and future risk of heart attack or stroke – an association that also appeared in two other cohorts of nearly 3,000 people, combined, from the US and Denmark.

This led Hazen and colleagues to investigate potential mechanisms by which erythritol might increase risk, with lab studies using blood samples from a small group of eight healthy volunteers.

Blood erythritol levels peaked and remained high for two to three days after volunteers downed an erythritol-sweetened drink, before returning to normal. Adding erythritol to whole blood samples also increased blood stickiness and other measures linked to blood clotting, with similar effects seen in animal studies.

It goes some way to showing how consuming high levels of artificial sweeteners could possibly trigger a cascade of changes in the blood that may lead to a cardiovascular event.

"[T]his paper effectively shows multiple pieces of a jigsaw exploring the effects of erythritol," says Aston University dietitian Duane Mellor.

But he says the study does not rule out other sources of erythritol in the blood, which can also be made from other sugars inside our bodies, particularly if we eat lots and move little.

The amount of added erythritol that volunteers consumed was also significantly higher than quantities permitted in store-bought drinks in the UK. But the study authors argue their chosen amount reflects the daily intake of some Americans.

Regulatory agencies are alert to the potential health risks of artificial sweeteners; their job is to figure out what levels of food additives are safe to consume based on the available evidence.

Just last year, a study involving more than 100,000 volunteers from France flagged an increased risk of heart disease with greater dietary intake of artificial sweeteners, which participants recorded daily.

Observational studies such as this better reflect people's usual diets, but aren't without their shortcomings. The challenge is sifting through the many other lifestyle factors that also affect heart health in big ways, such as physical activity, and trying to isolate the possible effects of one particular food or food additive from entire diets.

Nutritional epidemiologist Nita Forouhi of the University of Cambridge says the latest study extends previous research on the potential health harms of artificial sweeteners and its findings warrant further investigation.

However, because people in the study already had a lot of cardiovascular risk factors, it's hard to generalize the study findings to healthy populations. Three-quarters of the study participants had high blood pressure or coronary artery disease, and one-fifth had diabetes.

Until we know more about the long-term health effects of erythritol and other artificial sweeteners, it's probably best to stick to what we know is good for our general health: reducing our sugar intake by cutting down on sweetened drinks and highly processed foods of all varieties.

"Individual artificial sweeteners are not currently reported upon which makes their tracking difficult as well as limit the ability to readily research their health impacts," says Forouhi.

The research has been published in Nature Medicine.

Editor's note (1 March 2023): Paragraphs five and six have been added to the article to highlight criticism over the study earlier in the piece.