The consumption and use in the United States food supply of nonnutritive sweeteners (NNS) is widespread and increasing. Data indicate that more than 40% of adult Americans consume NNS daily, a percentage that is likely higher with studies measuring NNS in blood and urine having showed that many people who report not consuming NNS are actually doing so unknowingly. However, the long-term health impacts of NNS—including aspartame, sucralose, and stevioside—are not well known.

Synthesizing Current Evidence

For a study published in the Canadian Medical Association Journal, Meghan Azad, PhD, and colleagues synthesized current evidence regarding the long-term impact of the consumption of NNS seen in the general population on a range of cardiometabolic outcomes. “Previous systematic reviews had not addressed this specific question,” says Dr. Azad. “For example, some didn’t focus on long-term associations and effects, or they looked only at obesity but not other cardiometabolic outcomes like diabetes or heart disease. Also, there had been new studies published that were not captured in previous reviews and meta-analyses.”

Dr. Azad and colleagues identified 37 eligible studies, consisting of seven randomized trials and 30 observational studies. Trials looking at the issue at hand averaged only 6 months long and only enrolled overweight or obese participants, not reflecting the general population consuming NNS regularly for many years. On the other hand, observational studies averaged 10 years long and enrolled people from the general population, but these studies were subject to self-reporting bias and did not distinguish between sources of NNS (food vs beverage) or type of NNS, explains Dr. Azad.

Pooled Results

While the researchers found no clear evidence for a long-term benefit from NNS, they did find evidence of potential harm from the long-term consumption of NNS. This evidence was not found in the randomized trials the team analyzed, as none showed a significant effect of NNS on the outcomes examined, including BMI, weight, waist circumference, and cardiometabolic risk. However, in cohort studies, there were significant associations between higher NNS intake and some of these outcomes (Table). “For example, there was a 14% increased risk of type 2 diabetes in people who consumed higher amounts of artificial sweeteners,” says Dr. Azad.

Although the study team did not review studies addressing biological mechanisms, Dr. Azad highlights three theories that may help explain why NNS may be associated with increased BMI and cardiometabolic risk:

  1. “Gut bacteria partially determine how much energy is absorbed from food, and research has shown that certain combinations of gut bacteria promote excess weight gain.  Recent studies show that artificial sweeteners (at least in rats and adult humans) can disrupt the gut microbiome. Routinely consuming artificial sweeteners may be selecting for an ‘obesogenic’ microbiome.
  2. The body is programmed to respond to sugar in a specific way, and some of these responses are triggered by the perception of sweet taste. With artificial sweeteners, people get the perception of sweetness without having actual sugar to metabolize. There is some evidence that routine consumption of artificial sweeteners may confuse and ‘reprogram’ metabolism in a way that favors increased weight gain, high blood sugar, and insulin resistance.
  3. Consuming artificial sweeteners may promote a ‘sweet tooth’, leading to higher consumption of high-calorie foods. Consuming low or no-calorie sweeteners may also give people a sense of ‘permission’ to eat higher-calorie foods because they ‘saved’ on calories with their diet soda, for example.

Important Implications

“Overall, we found there is a lack of evidence on this topic,” stresses Dr. Azad. “Our results send a strong message to researchers and research funding bodies that more studies are needed to understand the long-term health impact of artificial sweeteners.” She adds that more accurate measures of NNS intake are needed—such as better survey questions and biological measurements—as are approaches to better distinguish between the types and sources of sweeteners. “How NNS impact health needs to be better studied,” she continues. “By understanding the mechanisms, whether or not the associations between NNS and cardiometabolic outcomes are causal can be better evaluated, hopefully leading to the development of alternative strategies.”

In the meantime, Dr. Azad suggests that physicians counsel their patients to think carefully about consuming NNS, particularly on a regular basis. “People are generally consuming NNS believing they are a ‘healthy choice,’ but this may not be true,” she concludes.