Are sugar substitutes healthy? Research doesn't yet offer comforting answers.

To satisfy the public's craving for sweetness and concern about the health effects of sugar, food companies have increasingly turned to sugar substitutes. Natural and artificial sweeteners are added to everything from sodas to toothpaste, lip balm to snack items.

Now, studies are raising concerns about the health effects of these substitutes.

Late last month, a study associated the sugar substitute erythritol with an increased risk of stroke. Although the research was far from definitive, it raised the question of what sugar substitute – if any – is healthiest.

Unfortunately, that's not an easy question to answer.

All sweeteners on the market have met the government's standard of being "generally recognized as safe," meaning research has shown they are not toxic.

But just because something isn't toxic doesn't mean it's healthy – or that it's helpful for weight management or disease prevention, said Allison Sylvetsky, an associate professor at The Milken Institute School of Public Health at the George Washington University.

"There has been more and more research showing that these low-calorie sweeteners are not inert and they do have health effects," she said.

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Concerns about sugar substitutes

The long-term effects of sugar substitutes are largely unknown. Most of the safety studies done are short-term because it is difficult and costly to do yearslong trials.

Each sugar substitute has different chemical structures and needs to be considered separately, said Dr. Walter Willett, a nutrition researcher at the Harvard T.H. Chan School of Public Health.

"We can’t generalize, and for most of these we have very limited data on the effects of long-term use," he said via email.

But studies have suggested that some sweeteners may exacerbate diabetes risk and disturb the balance of good and bad microbes in the gut, Sylvetsky and other researchers said.

It's hard to tell what's cause and what's effect, though, because people who consume more low-calorie sweeteners might already be vulnerable or have an illness such as diabetes, which is why they're eating "diet" or "no sugar added" products in the first place, said Sylvetsky.

A 2017 paper from Canadian researchers concluded that sweeteners consumed for weight management might actually lead to weight gain.

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British physiology researcher Havovi Chichger said her studies suggest that chemicals our bodies perceive as "sweet" can activate receptors throughout the body, including in the heart, the lung and the lining of the blood vessels.

"They're doing something very significant but we don't fully understand what," said Chichger, an associate professor in biomedical science at Anglia Ruskin University in England.

So far, her research shows aspartame, sucralose and saccharine all activate these sensors and in high doses can cause glucose intolerance, the first step toward diabetes.

In a study published last August in Cell, 120 volunteers were randomly assigned to consume aspartame, saccharin, sucralose or stevia over two weeks at doses below what's generally considered acceptable. Each substitute changed the participant's gut microbes, but in different ways. Saccharine and sucralose significantly altered their glucose tolerance, suggesting they can contribute longer term to metabolic disease, including diabetes.

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Chichger and others worry that these sweeteners have now become so ubiquitous that they're hard to avoid.

"In smaller quantities, as they were originally meant to be had, I think sweeteners can be a useful weight-loss tool, which is good for people," she said.

But while "everyone thought they were perfectly fine to have," Chichger said, "I think we now understand that's not the case."

No, sugar probably isn't better

Decades of research supports the idea that sugar can damage human health. Experts say sugary drinks are the worst, but replacing these drinks with artificially sweetened ones isn't the answer.

Too much sugar clearly disrupts the body's metabolism, potentially leading to diabetes, high blood pressure, cholesterol and an increased risk for heart attack and stroke.

"It is very well validated, that sugar is at least as metabolically harmful as any of the sweeteners, so our results and conclusions with sweeteners are by no means any sort of recommendations to revert to sugar," said Dr. Eran Elinav, head of the systems immunology department at the Weizmann Institute of Science in Israel, and a leading researcher on artificial sweeteners.

Sodas are particularly harmful, he said, because they add calories but no nutrients.

"Our recommendation is to stick with water as much as possible," Elinav said.

Tea and coffee probably offer some modest health benefits and are worth drinking along with water, Willett said.

For people who have a hard time giving up sweet drinks, Willett said, "using an artificially sweetened beverage can be like a nicotine patch is to smoking: Better than the real thing but best considered as a bridge to water, tea, or coffee."

It's also best to avoid foods with a lot of added sugar, such as most desserts, Willett said, and "not worry about adding a teaspoon or two of natural sugar when desired." 

The current Dietary Guidelines for Americans advise that sugar should account for less than 10% of total calories. The American Heart Association recommends even less added sugar: no more than 100 calories per day, or about 6 teaspoons, for most children and adult women, and no more than 150 calories per day, or about 9 teaspoons, for most men.

Each teaspoon of sugar has 16 calories and there are about 10 teaspoons in one 12-ounce can of Coke, for example.

"Reducing added sugar is absolutely necessary," Sylvetsky said, "but we need to be at least cognizant of the potential unintended consequences related to widespread replacement of added sugars with low-calorie sweeteners."

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Pros and cons of sweeteners

Not surprisingly, the food and beverage industry supports the availability and safety of sugar substitutes.

"Low- and reduced-calorie ingredients including sweeteners and dietary fiber offer consumers healthy alternatives and a greater variety of products from which to choose," said Robert Rankin, executive director of Calorie Control Council, an industry group, in an emailed statement.

“Evidence shows that low- and no-calorie sweeteners are a safe and effective alternative to added sugars and can be used as part of a balanced diet to help consumers achieve dietary goals, whether it be managing body weight or diabetes, reducing the consumption of added sugars, or reducing total caloric intake,” he said.

The International Sweeteners Association, an international nonprofit representing suppliers of low/no calorie sweeteners, added that "sweeteners are one of the most thoroughly researched ingredients in the world and have been proven safe by global regulatory bodies for decades."

The sweeteners are also accepted as safe in Europe and by the World Health Organization, association spokeswoman Alexandra Barnoux said via email. "At a time when obesity and non-communicable diseases, including diabetes, remain major global health challenges, low/no calorie sweeteners provide consumers choice with safe alternatives to reduce sugar and calorie intake."

But longtime industry critic Marion Nestle, an emeritus professor at New York  University, said the food industry underplays the health concerns around sweeteners.

"The makers and commercial users of sugar substitutes want us to keep buying their products and do everything they can to convince you the sweeteners are delicious, harmless, and good for you, regardless of what critics say," she said via email. "The new studies coming out that associate these chemicals with chronic disease are not good for corporate bottom lines, which is why they so actively cast doubt on inconvenient research."

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Bottom line

In a half-dozen interviews and requests for comment, researchers called for more study of sugar substitutes.

Sylvetsky said she's particularly concerned about low-calorie sweeteners being added to products marketed to children – on boxes decorated with cartoon characters and pictures of fruit –  often with claims of "reduced sugar."

"It's really confusing to parents," she said, adding that there's been very little research on the health effects of low- and no-calorie sweeteners in children.

Because of the lack of research, Willett said, regularly eating sweeteners "is signing up for a long-term uncontrolled experiment."

Studies are underway to finally answer the question of what's the healthiest way to sweeten foods, Chichger said. This is an area of "massive interest" among researchers, she said, and "in the next few years, we should be able to answer a lot of the questions."

In the meantime, people who want to cut down on artificial sweeteners can read labels and make choices.

"I wouldn't say we need to avoid sweetness all the time," Sylvetsky said. "But simply replacing sugary drinks with diet drinks or replacing sugar with low-calorie sweeteners may not be effective for improving diet and health."

Contact Karen Weintraub at kweintraub@usatoday.com.

Health and patient safety coverage at USA TODAY is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Healthcare. The Masimo Foundation does not provide editorial input.

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This article originally appeared on USA TODAY: Sweetener safety: Are sugar substitutes bad for you? What science says