In these studies, people are randomly assigned to either an experimental group – which receives the experimental substance, such as a nonsugar sweetener – or a control group – which receives a placebo or different substance. Participants in both groups are then tracked for a period of time, typically weeks or months. The majority of studies involving randomized controlled trials on nonsugar sweeteners to date involve this type of comparison, with nonsugar sweeteners replacing consumption of natural sugar-sweetened beverages.

The analysis of almost 50 randomized controlled trials on which the WHO based its recommendation found modest benefits of using nonsugar sweeteners for weight loss and determined that the habitual use of those nonsugar sweeteners did not lead to diabetes symptoms or indicators of cardiovascular disease. But it did find that the use of nonsugar sweeteners was associated with a higher ratio of total cholesterol to HDL, short for high-density lipoprotein, which is considered the "good cholesterol.”

That means that habitual consumers of artificial sweetener had more of the low-density lipoprotein, or LDL version, in their system. That form of “bad cholesterol” is a risk factor for heart disease.

However, other potential adverse consequences of consuming nonsugar sweeteners may take more time to appear than can be identified in the limited time frame of a randomized controlled trial.

The authors also evaluated what are called prospective cohort studies. Those studies track participants’ self-reported use of sweeteners alongside health outcomes, oftentimes over many years. They also took into account case-control studies, which identify people with or without a certain health issue, such as cancer, and then use available health records and interviews to determine the extent of nonsugar sweetener use in their past.

Examination of the cohort and case-control studies found that regular consumption of nonsugar sweetener was associated with increased fat accumulation, higher body mass index and increased incidence of Type 2 diabetes. Those findings differ from the outcomes of the randomized control studies.

Analysis of the cohort and case-control studies also concluded that a history of regular nonsugar sweetener use was linked to increased frequency of stroke, hypertension, other adverse cardiovascular events and, in pregnant people, an increased risk for premature birth. The frequency of cancer in nonsugar sweetener consumers was very low in general, though saccharin, an FDA-approved sweetener found in many food products, was associated with a bladder cancer.

On the face of it, these results are alarming, but they need to be taken with a grain of salt. As the WHO report points out, these studies have significant limitations that need to be considered.

Take, for example, in the cohort and case-control studies, that higher body mass index, or BMI, was associated with greater nonsugar sweetener intake and poorer health outcomes. One possibility is that people with obesity used nonsugar sweeteners to help cut calories more than others without obesity. This makes it difficult to determine whether the disease is caused by sustained artificial sweetener use or by the other underlying conditions associated with obesity.

Additionally, the way nonsugar sweeteners are consumed is not controlled in these types of studies. So negative health outcomes could be associated with other affiliated harmful behaviors, such as more sugar or fat in the diet.

The picture is very mixed on both the benefits of nonsugar sweeteners for weight loss and their ties to adverse health issues. The WHO’s recommendation seems to have weighed the cohort and case-control studies over the randomized controlled ones, a decision that we found puzzling in light of the limitations of these studies for assessing whether nonsugar sweeteners have a causal role in disease.

As with all health-related choices, the science is complex. In our view, grabbing a diet drink to offset the calories in a slice of chocolate cake every once in a while will likely not be harmful for your health or lead to a significant weight change.

This article is republished from The Conversation, an independent nonprofit news site dedicated to sharing ideas from academic experts. The Conversation is trustworthy news from experts, from an independent nonprofit. Try our free newsletters.

Read more:
What’s the difference between sugar, other natural sweeteners and artificial sweeteners? A food chemist explains sweet science

Sweeteners may be linked to increased cancer risk – new research

Lindsey Schier receives funding from the National Institutes of Health (NIDCD).

Scott Kanoski receives funding from the National Institutes of Health.