Study strengths
Dr. Touvier acknowledged that dietary studies, which generally rely on individuals self-reporting food and drink intake, are always hard to interpret. But she said this study used a more reliable method of dietary assessment, with repeated 24-hour dietary records, which were validated by interviews with a trained dietitian and against blood and urinary biomarkers.
And whereas residual confounding cannot be totally excluded, she pointed out that models were adjusted for a wide range of potential sociodemographic, anthropometric, dietary, and lifestyle confounders.
Dr. Touvier also noted that cases of cardiovascular disease in the first 2 years of follow-up were excluded to minimize the bias caused by individuals who maybe have switched to artificial sweeteners because of a cardiovascular issue.
“While this study has many strengths, it cannot on its own prove a causal relationship between artificial sweetener and increased cardiovascular risk,” she added. “We need health agencies to examine all the literature in the field. This is however another important piece of evidence.”
Dr. Touvier says that although observational studies have their issues, they will form the basis of the evidence on the effects of artificial sweeteners on health.
“Randomized studies in this area can only really look at short-term outcomes such as weight gain or biomarker changes. So, we will have to use observational studies together with experimental research to build the evidence. This is what happened with cigarette smoking and lung cancer. That link was not established by randomized trials, but by the accumulation of observational and experimental data.”
Different artificial sweeteners may be better?
Commenting on the study, Kim Williams Sr., MD, University of Louisville (Ky.), pointed out that this study included artificial sweeteners that increase insulin or decrease insulin sensitivity, and that insulin spikes increase obesity, insulin resistance, hypertension, and atherosclerosis.
“There are some safer artificial sweeteners that do not increase insulin much or at all, such as erythritol, yacon root/yacon syrup, stevia root, but they weren’t included in the analysis,” Dr. Williams added.
Dr. Sievenpiper explained that most studies on artificial sweeteners look at their consumption in isolation without considering how they compare to the intake of the sugars that they are intended to replace.
“The comparator matters as no food is consumed in a vacuum,” he said.
To address this, Dr. Sievenpiper and colleagues have recently published a systematic review and meta-analysis of the prospective cohort study evidence that shows if exposure to artificially sweetened beverages is modeled in substitution for sugar-sweetened beverages, then they are associated with less coronary heart disease, cardiovascular mortality, and all-cause mortality.
On the other hand, if exposure to artificially sweetened beverages is compared with water, then no difference in these outcomes was seen.
“These observations are more biologically plausible, robust, and reproducible and agree with the evidence for the effect of artificial sweeteners on intermediate risk factors in randomized trials,” Dr. Sievenpiper notes.
His group has also recently published a review of randomized studies showing that when compared with sugar-sweetened beverages, intake of artificially sweetened beverages 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,” Dr. Sievenpiper concludes.
The current study was funded by the European Research Council under the European Union’s Horizon 2020 research and innovation program, French National Cancer Institute, French Ministry of Health, IdEx Université de Paris Cité, Bettencourt-Schueller Foundation Research Prize 2021. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.