A new meta-analysis and systematic review finds mixed evidence to support use of artificial sweeteners for weight loss and suggests routine consumption may be associated with long-term weight gain and an increased risk of cardiometabolic disease^[1].

“People are generally consuming nonnutritive sweeteners (NNS) believing they are a ‘healthy choice,’ but this may not be true,” study author Dr Meghan Azad (University of Manitoba, Winnipeg) told theheart.org | Medscape Cardiology in an email.

“More important, our results send a strong message to researchers and research funding bodies that more studies are needed to understand the long-term health impacts of artificial sweeteners.”

The lack of studies looking at long-term effects is surprising, given that more than 40% of adult Americans regularly consume NNS, such as aspartame, sucralose, and stevia, she said. In addition, studies measuring NNS in blood and urine show that many people who report not using NNS are unknowingly consuming these sweeteners in foods.

The study, published July 17, 2017 in CMAJ, pooled results from seven randomized controlled trials with 1003 participants (median follow-up 6 months) and 30 cohort studies with 405,907 participants (median follow-up 10 years).

In participants who were obese or overweight, two longer trials showed significant weight loss with NNS over 16 to 24 months and three shorter trials showed no effect with NNS use over 6 months. Both of the longer-term trials, however, were industry sponsored, and all five trials were at high risk of bias, the authors noted.

Two trials involving mildly hypertensive patients who were taking stevioside capsules and one in overweight participants showed no significant effect on BMI over 6 to 24 months (mean difference -0.37 kg/m²; 95% CI -1.10 to 0.36).

Large cohort studies with longer follow-up, however, showed that high NNS intake was significantly associated with modest long-term gains in body weight, BMI, and waist circumference.

In addition, high NNS intake was associated with higher risks of hypertension (hazard ratio [HR] 1.13, 95% CI 1.06–1.20), stroke (risk ratio [RR] 1.14, 95% CI 1.04–1.26), cardiovascular events (RR 1.32, 95% CI 1.15–1.52), and incident type 2 diabetes (RR 1.14, 95% CI 1.05–1.23).

Notably, there were no data from the trials to confirm these observations, and the increased risk for type 2 diabetes found in nine cohort studies was attenuated (RR 1.07, 95% CI 0.97–1.18) after imputing missing studies, suggesting potential publication bias, the authors write.

Dr Lawrence Cheskin (Johns Hopkins Weight Management Center, Baltimore, MD) said, “Even though they point to some observational studies and say there is more diabetes, there’s no experimental evidence that that occurs in humans. Nor heart disease.”

He feels it is unlikely  that artificial sweeteners directly cause heart disease. “It may be associated with people who have somewhat higher risks of heart disease because they’re heavier and have bad habits and are drinking diet soda to make up for the other things they’re doing that aren’t so good,” he speculated.

In addition to the confounding factor of selection bias, Cheskin pointed out that the seven randomized trials were in small numbers of people followed for relatively short periods of time and looked only at certain types of sweeteners available at the time and in beverages, not in other foods. In four of the trials, participants using NNS were also on a weight-loss program.

For its part, the Academy of Nutrition and Dietetics, the largest organization of food and nutrition professionals in the US, says NNS play a role in weight and blood glucose control.