Artificial sweeteners linked to higher CV event risk

Health concerns about the consumption of artificial sweeteners could be heightened by the publication of a new study linking their consumption to an increased risk of heart disease and stroke.

In this latest large-scale prospective study of French adults, total consumption of artificial sweeteners from all sources was associated with an overall increased risk of cardiovascular and cerebrovascular disease.

The study was published online in the BMJ September 7.

The current study differs from those done previously in that it includes intake of artificial sweeteners from both food and beverages, whereas previous studies have primarily focused on the artificial sweetener content of beverages alone. .

“Here, we have quantified for the first time the global exposure to artificial sweeteners. It is not just about beverages, but also the use of table-top sweeteners and other foods containing artificial sweeteners such as yogurts and desserts. This is the first time this information has been correlated with heart disease risk,” said lead author Mathilde Touvier, MD, Sorbonne University Paris Nord, France. | Medscape Cardiology.

Just over half of artificial sweetener consumption in the study came from beverages, with the rest from table-top sweeteners and food.

“We included severe cardiovascular and cerebrovascular clinical endpoints such as heart attack or stroke, and our results suggest that the amount of artificial sweetener in less than a can of soda may increase the risk of such events” , noted Touvier.

“This is a large and statistically significant association that shows the robustness of all models after adjusting for many other possible confounders,” she said.

“There is now a growing body of evidence linking artificial sweeteners to weight gain and heart disease,” she concluded. “My advice would be that we should all try to limit sugar intake, but we shouldn’t consider artificial sweeteners as safe alternatives. Instead, we should try to reduce our need for sweetness in our diets.”

But another leading researcher in the field urges caution in interpreting these results.

John Sievenpiper, MD, Departments of Nutritional Sciences and Medicine, University of Toronto, Canada, commented | Medscape Cardiology: “This paper shows the same relationship observed by many other large prospective cohorts that model artificial sweetener consumption as baseline or prevalent exposures.

“These observations are well recognized as having a high risk of residual confounding due to behavioral clustering and reverse causation in which cardiovascular disease risk drives people to consume artificial sweeteners as a strategy to mitigate that risk, as opposed to ‘reverse.”

Risk increased by 9%

The present study included 103,388 French adults from the NutriNet-Santé cohort, 37.1% of whom reported having consumed artificial sweeteners. The sweeteners assessed were primarily aspartame (58% of sweetener intake), acesulfame potassium (29%) and sucralose (10%), with the remaining 3% consisting of various other sweeteners including cyclamates and saccharin.

The results showed that over an average follow-up of 9 years, the consumption of artificial sweeteners was associated with a 9% increased risk of cardiovascular or cerebrovascular events, including myocardial infarction, acute coronary syndrome, angioplasty, angina pectoris, stroke or transient ischemic attack, with a risk ratio of 1.09 (95% CI, 1.01 to 1.18; P = .03).

The average consumption of artificial sweeteners among those who reported consuming them was 42.46 mg/day, which corresponds to approximately one individual sachet of table-top sweetener or 100 ml of diet soda.

“We don’t have enough evidence to determine a harmful amount of artificial sweetener, but we showed a dose-response association, with a higher risk of cardiovascular events with higher consumption,” Touvier said.

“The higher consumption in this study was an average of 77mg/day of artificial sweetener, or about 200ml of soda – just slightly less than a standard can of soda,” she added.

The absolute incidence rate of cardiovascular or cerebrovascular events among heavy users was 346 per 100,000 person-years versus 314 per 100,000 person-years among non-users.

Further analysis suggested that aspartame consumption was particularly associated with an increased risk of cerebrovascular events, while acesulfame potassium and sucralose were associated with an increased risk of coronary heart disease.

Study Highlights

Touvier acknowledged that dietary studies, which typically rely on individuals self-reporting their food and beverage intake, are always difficult to interpret. But she said this study used a more reliable dietary assessment method, with repeated 24-hour dietary records, which were validated by interviews with a trained dietitian and against blood and urine biomarkers.

And while residual confounding cannot be ruled out entirely, she pointed out that the models were adjusted for a wide range of potential sociodemographic, anthropometric, dietary and lifestyle confounders.

Touvier also noted that cases of cardiovascular disease in the first 2 years of follow-up were excluded to minimize bias caused by people who may have switched to artificial sweeteners due to a cardiovascular issue.

“While this study has many strengths, it alone cannot prove a causal relationship between artificial sweetener and increased cardiovascular risk,” she added. “We need health agencies to review all the literature in the area. This is another important piece of evidence, however.”

Touvier says that while observational studies have their problems, they will form the evidence base on the health effects of artificial sweeteners.

“Randomized studies in this area can only really look at short-term outcomes such as weight gain or biomarker changes. So we’ll have to use observational studies along with experimental research to establish the evidence. That’s what happened with smoking and lung cancer.This link has not been established by randomized trials, but by the accumulation of observational and experimental data.

Different artificial sweeteners may be better?

Commenting on the study of | Medscape CardiologyKim Williams Sr, MD, University of Louisville, Kentucky, pointed out that this study included artificial sweeteners that increase insulin or decrease insulin sensitivity, and insulin spikes increase obesity, resistance to insulin, hypertension and atherosclerosis.

“There are safer artificial sweeteners, which do not raise insulin much or at all, such as erythritol, yacon/yacon root syrup, stevia root, but they have not been included in the analysis,” added Williams.

Also commenting for | Medscape CardiologySievenpiper explained that most studies of artificial sweeteners look at their consumption in isolation without considering how they compare to intake of the sugars they are meant to replace.

“The comparator is important because no food is eaten in a vacuum,” he said.

To address this issue, Sievenpiper and colleagues recently published a systematic review and meta-analysis of prospective cohort study evidence that shows that if exposure to artificially sweetened beverages is modeled as a replacement for sugary beverages, they are therefore associated with less coronary heart disease. , cardiovascular mortality and all-cause mortality.

On the other hand, if the exposure to artificially sweetened beverages is compared to water, no difference in these results was observed.

“These observations are more biologically plausible, robust and reproducible and consistent with evidence for the effect of artificial sweeteners on intermediate risk factors in randomized trials,” notes Sievenpiper.

His group also recently published a review of randomized studies showing that, compared to sugary drinks, drinking artificially sweetened drinks was associated with small improvements in body weight and cardiometabolic risk factors without evidence of harm.

“I think the context provided by these studies is important, and taken together, the totality of the evidence suggests that artificial sweeteners are likely to be a useful tool in sugar reduction strategies,” Sievenpiper concludes.

This study was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme, the French National Cancer Institute, the French Ministry of Health, the IdEx Université de Paris Cité, the 2021 Bettencourt-Schueller Foundation Research Prize. The authors have not disclosed any relevant financial relationships.

BMJ 2022. 2022;378:e071204. Full Text

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