Artificial Sweetener Intake Linked to Increased Risk of CVD in Large, Population-based Analysis

High intake of artificial sweeteners may increase risk of cardiovascular, cerebrovascular, and coronary heart disease, according to new research findings.

Authors of the web-based study, which drew on data from more than 100 000 individuals, also report a differential impact on cardio- and cerebrovascular health based on type of sweetener, with total intake linked to higher risk of cardiovascular disease (CVD0 and cerebrovascular disease, aspartame intake with increased risk of cerebrovascular events, and acesulfame potassium and sucralose associated with increased coronary heart disease (CHD) risk.

Charlotte Debras, a PhD candidate at Sorbonne Paris Nord University, and colleagues from the University of Paris and French Network for Nutrition and Cancer Research write that although the replacement of sugar with the nonnutritive sweeteners was originally met with enthusiasm by consumers and health care professionals alike, numerous studies have investigated early markers of CV health, eg, weight status, hypertension, inflammation, and vascular dysfunction, in association with their use in food and beverages. Despite mixed results, the authors say, the body of evidence supports a role for the additives in CV health as well as “plausible mechanisms.”

The objective of their research, a large-scale, prospective, population-based study, was to leverage quantitative data to better explore potential links between artificial sweetener intake (mg/day) from all dietary sources overall, by type (aspartame, acesulfame potassium, sucralose), and by risk of CVD (overall, coronary, and cerebrovascular).

The objective of their research, a large-scale, prospective, population-based study, was to leverage quantitative data to better explore potential links between artificial sweetener intake (mg/day) from all dietary sources overall, by type (aspartame, acesulfame potassium, sucralose), and by risk of CVD (overall, coronary, and cerebrovascular).

The research team tapped the French web-based NutriNet-Santé e-cohort that contains data from more than 170 000 adults aged ≥15 years who provided details about diet, health, anthropometrics, lifestyle and sociodemographic features, and physical activity at enrollment. The e-cohort also includes granular information on commercial brands of food consumed. Using NutriNet-Santé data from 2009 to 2021, Debras and colleagues examined a total of 103 388 participants for the analysis, a cohort that was 79.8% women and had a mean age of 42.2 years at baseline. The final sample comprised 904 206 person-years of follow-up data.

Participants were stratified according to intake of artificial sweetener into 3 groups:
•higher consumers 77.62 mg daily (18.51%)
•lower consumers 7.46 mg daily (18.59%)
•non-consumers 0 mg daily (62.9%)

FINDINGS

The investigators found overall that 37.1% of the cohort reported consumption of artificial sweeteners, with an average daily intake of 15.76 mg among all participants and 42.46 mg among consumers only. Among the participants who consumed artificial sweeteners, mean intake was 7.46 mg/day for lower and 77.62 mg/day for higher consumers.

The associations between use of sweeteners and cardiovascular risk were estimated using multivariable-adjusted Cox hazard models, according to the study.

Total artificial sweetener intake, report Debras and colleagues, was linked to an increased risk of cardiovascular disease (HR, 1.09 [95%CI, 1.01-1.18]; P=.03) with absolute incident rates per 100 000 person years recorded as 346 and 314 for higher consumers and lower consumers, respectively.

The investigators found that among participants who consumed higher amounts of artificial sweetener, risk for developing cerebrovascular disease was significantly greater than among non-consumers (HR = 1.18; 95% CI, 1.06 to 1.31). When they analyzed consumption of individual sweeteners, the researchers found that aspartame consumption was associated with an increased risk of cerebrovascular events (HR, 1.17 [95% CI, 1.03-1.33]; P=.02) while higher intake of acesulfame potassium (HR, 1.40 [95% CI, 1.06-1.84]; P=.02) and sucralose (HR, 1.31 [95% CI, 1.00-1.71]; P=.05) were associated with increased risk of CHD.

The authors state that the study’s large sample size was a strength as was the assessment of artificial sweetener consumption at the individual level in a population-based cohort. Residual confounding cannot be completely excluded, they add, nor can causal relations be established from an observational study. Thus, they caution against generalizing to the French population, or any population at large.

“These findings suggest that higher artificial sweetener consumption might be associated with increased risk of CVDs,” the team writes in conclusion. “Further well-designed, large-scale prospective studies need to confirm these results and experimental studies should be conducted to clarify biological pathways.

“In the meantime, this study provides key insights into the context of artificial sweetener re-evaluation by the EFSA [European Food Safety Authority], WHO, and other health agencies worldwide,” investigators added.

Reference: Debras C, Chazelas E, Sellem L, et al. Artificial sweeteners, and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort. BMJ. 2022;378:e071204. doi:10.1136/bmj-2022-071204