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There’s mounting evidence that artificial sweeteners may be linked to heart disease and other possible health risks. Scientists say the findings are far from definitive, however, with some leading researchers calling for better-designed clinical trials investigating the long-term health effects of sugar substitutes.

That’s why, in separate trials, researchers are actively working to get a clearer understanding of how artificial sweeteners affect blood glucose levels, gut microbiome health and the cardiovascular system. Some studies are beginning to compare the alternatives against each other, while others hope to learn how they affect the body compared to sugar.

As it is, it’s difficult for consumers to determine which sugar alternative carries the fewest health risks. Most of the research is observational, meaning it doesn’t prove cause and effect. In some cases, researchers looked at people who ate nonsugar sweeteners, analyzed their incidence of certain health risks like heart attacks or diabetes, then noted associations between the two.

All the widely consumed alternatives such as saccharin, aspartame, sucralose, stevia, xylitol and erythritol are approved by the Food and Drug Administration. They’re found in countless products including sports drinks, energy bars, yogurts, cereals, beverages, candies, baked goods and syrups.

Even with FDA approval, Dr. Dariush Mozaffarian, a cardiologist and professor of nutrition science and policy at Tufts University, said “they’re all potentially worrisome and all understudied.”

In recent research, cardiologist Dr. Stanley Hazen at the Cleveland Clinic found that the high concentrations of the sugar alcohol sweeteners xylitol and erythritol may cause the platelets in the blood to become more sticky and prone to clotting, in turn raising the risk of heart attack and stroke. The phenomenon is similar to what happens with high cholesterol, Hazen said. If they get big enough, the clots can block blood flow through crucial veins and arteries.

Some experts say that instead of trying to pinpoint the safest nonsugar sweetener, better studies need to determine whether there’s a benefit to swapping out sugar in the first place.

After publishing research finding a connection between erythritol and increased risk of heart attack and stroke, Hazen and his colleagues conducted the first head-to-head human trial comparing the effects of consuming erythritol versus sugar on the blood platelets that control clotting. The results of that study are pending publication.

Vasanti Malik, an assistant professor of nutritional sciences at the University of Toronto, meanwhile, is conducting a study of more than 500 people directly comparing the health effects of drinking sugar-sweetened beverages, noncaloric sweeteners or water. Malik and her colleagues plan to measure obesity and heart health over time.

At Virginia Tech, registered dietitian Valisa Hedrick is working with the National Institutes of Health on another study comparing the effects of four different artificial sweeteners versus sugar on blood glucose levels and gut microbiome health. The study, which focuses on people with prediabetes, is a controlled feeding trial, meaning participants only eat the meals that NIH provides them, and nothing more.

This is important, Hedrick said, because one of the growing concerns with nonsugar sweeteners is that the products trick the brain in such a way that they increase sugar cravings. People may then end up eating more sugar throughout the day, spiking their blood glucose.

With a controlled study, the researchers can answer whether the sweeteners themselves raise blood glucose directly — not the sugar people could otherwise eat later.

The limits of sweetener studies

A research bias called reverse causation can make it difficult to draw decisive conclusions from prior studies, Malik said.

People often change their diets after they start developing diabetes or putting on weight, Malik said. These people, generally, are most likely to switch from sugar to nonsugar sweeteners. This is where the reverse causation comes into play.

“You get a spurious association between the intake of nonsugar sweeteners and the risk for diabetes,” she said. That is, the data ends up suggesting that these sweeteners are causing health problems that already existed.

Many studies also rely on people to report whether they’ve consumed nonsugar substitutes, which can be unreliable. Names like xylitol can be buried in a long list of ingredients.

Other studies, meanwhile — like Hazen’s erythritol and xylitol studies — may focus directly on what happens in the body after someone consumes one of these sweeteners, but they tend to enroll small numbers of people and track them only for a short time.

“A lot of these studies are really hard to interpret,” said Dr. Michelle Pearlman, a gastroenterologist and the CEO and co-founder of the Prime Institute in Miami. “And the problem is that there’s no head-to-head trials of people eating candy bars versus xylitol, so I can’t make any blanket statements recommending one or the other.”

Both Hedrick and Malik hope to share results from their respective studies in the next several years.

“We need experimental science alongside more rigorous observational research,” Malik said. “There are trials underway, and I think in the next five years we’ll have more clarity on the topic. We’re just not quite there.”

In a statement, the Calorie Control Council, an industry trade group representing more than two dozen sweetener manufacturers, said studies linking alternative sweeteners to health risks are based on flawed research and that the products are safe.

“It is irresponsible to amplify faulty research to those who look to alternative sweeteners to reduce overall sugar intake as well as the millions who use it as a tool to manage their health conditions, including obesity and diabetes,” Carla Saunders, the trade group’s president, said in the statement.

Why it’s important to know

Most low-calorie and sugar-free foods contain at least one sugar substitute, and many contain several. These products are growing more popular, especially in the U.S. By 2033, market research suggests sugar substitutes could be worth more than $28.57 billion.

“They’re ubiquitous,” Mozafarrian said. “And they’re proliferating because people have become so obsessed with avoiding sugar.”

Mozaffarian said these sweeteners soared in popularity following changes to U.S. nutrition labeling requirements in 2016.

The change required manufacturers to list added sugars on a separate line beneath total sugars. The idea was to help consumers differentiate between foods with naturally occurring sugars, like fruit and plain Greek yogurt, and foods that had sugars mixed in.

“Now, the food industry has a big incentive to make that ‘added sugars’ number as small as possible,” he said. “So you’re seeing these compounds in everything, and we still don’t have enough information on them.”

Some products are labeled as “artificial sweeteners” or “natural sweeteners” based on whether they’re derived from natural sources or chemically engineered.

Even natural sweeteners go through heavy chemical processing, said Dr. Maria Carolina Delgado-Lelievre, a cardiologist at the University of Miami.

For example, stevia comes from processed stevia plant extract, monk fruit sweetener comes from processing a chemical in a gourdlike fruit grown in China, and sucralose is a chemically altered version of sugar about 600 times sweeter, according to the FDA.

Aspartame and saccharin are from human-made fusions of amino acids and chemicals.

Many of these sweeteners are so potent in tiny quantities that they’re mixed with xylitol or erythritol to bulk them up and fill a packet, said the Cleveland Clinic’s Hazen.

Given this label confusion, Hedrick said researchers are increasingly using the term “nonsugar sweeteners.”

Health risks of added sugars

Sugar, of course, is one of the country’s most pressing public health problems. Especially in soda and juice, excess sugar fuels the ongoing obesity epidemic, contributing to heart disease, liver disease, cancer and diabetes.

However, there’s a big difference between processed, concentrated sugars like high-fructose corn syrup and the natural sugars found in fruits, Pearlman, the Miami gastroenterologist, said. Processed sugars are highly addictive.

“Anything with high-fructose corn syrup stimulates the same reward centers in our brain as cocaine and heroin,” she said. “Natural sugars from fruit act differently in the body.”

Sugar’s bad rap has much more to do with the quantity people consume than any intrinsically bad property, experts agree.

“Added sugar is nuanced,” Mozaffarian said. “When you try to take that very real nuance and turn it into a simple message, you get the industry misleading consumers that foods are ‘not good.’”

A little bit of added sugar in otherwise healthy foods, he said — such as lightly sweetened whole-grain cereals — is usually OK.

“The harms of these different nonsugar sweeteners have been greatly underemphasized and the harms of small amounts of added sugar have been overemphasized,” he argued.

Sugar substitutes for children?

The U.S. government’s Dietary Guidelines for Americans recommend that anyone over the age of 2 consume less than 10% of their daily calories from added sugar, or the equivalent of roughly 12 teaspoons of added sugar. In reality, as of 2018, people in the U.S., including children, were consuming about 17 teaspoons of added sugar per day, on average.

Recently, the U.S. Department of Agriculture implemented a new rule limiting added sugars in public school lunches. Michael Goran, a professor of pediatrics at the University of Southern California’s Keck School of Medicine, said he worries that schools will replace sugary foods with artificially sweetened foods to comply with the new rules.

“There’s this general perception that these sweeteners are safe alternatives, but if they’re broadly applied to children, I unfortunately think that’s very risky,” he said.

Mozaffarian said that at their current levels of added sugar, most yogurts would no longer be allowed in school lunches once the new rule goes into effect.

“They’re just above the new limit, so it’s likely these yogurts are now going to be made with a series of sweeteners with uncertain health effects,” Mozaffarian said.

In the meantime, Pearlman said, it’s easy to see they haven’t helped the population become healthier on the whole.

“We have more chronic disease, more diabetes today than we’ve ever had before,” she said. “That shows that despite the diet industry being worth billions of dollars, we’re clearly missing the ball.”

A confusing body of limited research, coupled with the lack of clarity on food labels, puts consumers in a tough position when it comes to selecting the healthiest choices, the experts concluded.

All agreed on the best solution:

  • Eat as many whole, unprocessed foods as you can.
  • The less processed a food, the less likely it is to be loaded with added sugars or nonsugar sweeteners.

“If I had the choice of eating a store-bought cookie with a lot of sweeteners in it, a store-bought cookie with monk fruit, or a homemade cookie with sugar, I would choose the homemade cookie,” Goran said. “You can still enjoy the cookie, but maybe put a little less sugar in there.”

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