If you think that consuming drinks and foods sweetened with low-calorie sugar substitutes like aspartame, saccharin, or stevia will help you lose weight, you might want to think again.

According to an analysis published Monday in the Canadian Medical Association Journal, these compounds may actually contribute more to weight gain than weight loss.

In one of the most comprehensive reviews to date, of research that has been notoriously muddy, scientists from the University of Manitoba's George & Fay Yee Centre for Healthcare Innovation examined 37 previously published studies that involved a total of 406,910 subjects. Their analysis exposed several gaps in our understanding of how low-calorie sweeteners work and what their effects are in both the short and long term. 

The findings come at a time when curbing sugar consumption is increasingly viewed as the quickest path to a trimmer waistline and better overall health. They serve as a reminder that when it comes to diet and nutrition, there are few easy answers and no real shortcuts.

A Puzzling Paradox

The authors evaluated both clinical trials (which allow scientists to test cause-and-effect relationships) and observational studies (which help them examine health impacts in real-life settings). They also looked at a wide range of outcomes: not just weight, but also stroke, hypertension, and cardiovascular disease.

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The clinical trials (which tended to be small, short, and focused on people who were obese and using low-calorie sweeteners in an effort to lose weight) failed to show a consistent link between low-calorie sweetener consumption and weight loss metrics such as body mass index (BMI), waist circumference, or pounds lost.

The observational studies (larger, longer, and focused on healthy people consuming these substances in their regular diet) found that people who used low-calorie sweeteners were actually more likely to gain weight and to see an increase in their BMI and waist circumference. They were also more likely to suffer from hypertension, cardiovascular disease, and strokes.

“Ultimately, we found no consistent proof that the sweeteners help reduce weight,” says Meghan Azad, a scientist at the Children’s Hospital Research Institute of Manitoba, and the study’s lead author. “And we found at least some evidence that they do the opposite.”

The American Beverage Association (ABA), a trade group, disputed the study's conclusions. “Low- and no-calorie sweeteners are among some of the most exhaustively researched ingredients in the world and have been approved as safe for consumption by government regulatory agencies worldwide, including the FDA [Food and Drug Administration],” says William M. Dermody, the ABA’s vice president of policy. “Nothing in this study shows otherwise.”

A Growing National Habit

With sugar now replacing fat as the chief villain in our daily diets, consumers are flocking to low-calorie replacements in droves. The current options include artificial sweeteners like aspartame (Equal, NutraSweet), saccharin (SugarTwin, Sweet'N Low), and sucralose (Splenda), sugar alcohols such as sorbitol and xylitol, and plant-based chemicals such as stevia (Pure Via, Truvia).

According to a 2017 study in the Journal of Academy of Nutrition and Dietetics, use of these sugar substitutes increased by 200 percent between 1999 and 2012, and about 41 percent of Americans now use them on a regular basis.

Some research suggests that the compounds are becoming so common that people may consume them without even realizing it. For example, another 2017 study, in the American Journal of Clinical Nutrition, detected traces of low-calorie sweeteners even in the urine of people who said they never consumed them.

“These compounds used to be just in beverages,” says Allison Sylvetsky Meni, an exercise and nutrition scientist at George Washington University and that study's lead author. “Now they're in everything from yogurt to salad dressing to sauces. Even cocoa almonds have low-calorie sweeteners. They pop up in lots of places you wouldn't expect.”

More Research Needed

While the current analysis was rigorous, its conclusions are still a long way from certain, Azad says. In fact, she says one of her team's biggest findings was just how many gaps remain in the research on low-calorie sweeteners. 

For example, the scientists were not able to compare different types of low-calorie sweeteners, or say whether the effects of consuming them in food is different than the effects of consuming them in beverages, because no such experiments have yet been conducted.

“When these longer-term studies first began, consumption patterns were very different and a lot of the sweeteners that we have now weren't available,” Azad says. “So we don’t really know yet what the impact will be of the way people are consuming these products today.”

And even if the link between low-calorie sweeteners and adverse outcomes like weight gain and hypertension holds, scientists will still have to figure out the underlying biology. That is, they will have to explain how, exactly, something low-calorie contributes to higher weight.

To be sure, they already have some hypotheses: It's possible that these sweeteners somehow stimulate the appetite so that people end up eating more. It's also possible that they alter the gut microbiome in ways that imperil fat metabolism. But it will take time to map those details out. 

Eat (and Drink) Smart

In the meantime, while there’s no cause to panic, it's important to think about what you're replacing your sugar with, and whether there's a healthier choice to make—especially if you are trying to lose weight. 

Read food labels. Most products that boast “no sugar added” are apt to contain sweeteners like the ones in the current study. But even products without those labels can be suspect. Amy Keating, a registered dietitian and Consumer Reports food tester, says that an increasing number of products contain both regular sugar and low-calorie sweeteners. Because the product doesn't in any way indicate that it's a low-calorie food, you might not think to check whether it contains low-calorie sweeteners.  

Skip the sugary drinks. An occasional soda or diet soda is probably fine. But generally speaking, you want to avoid them. They offer little nutritional benefit, and they have been known to cause headaches and may also trigger overeating“Water is best,” says Ralph L. Sacco, a professor of neurology at Miami Miller School of Medicine who has conducted numerous studies on artificial sweeteners. “Everything else in moderation.”

Stick with what works. Foods that contain low-calorie sweeteners may also contain a lot of other chemicals with uncertain health and safety profiles. By opting for whole foods such as fruits and vegetables, legumes, and whole grains—foods the U.S. Dietary Guidelines already recommend you eat more of—you will not only avoid these sweeteners, you may well avoid whatever the next flawed ingredient turns out to be.