Which sugar substitute is best for you? Here’s how they compare

When you pick up a low-sugar or low-calorie food, chances are it contains an artificial or plant-derived sweetener. Marketed as healthier swaps for sugar, these compounds aren’t just neutral stand-ins—they interact with the body in complex ways that go far beyond cutting calories.

With ordinary sugar, enzymes in the small intestine split it into glucose and fructose, and the glucose rapidly enters the bloodstream. “Glucose is the brain’s preferred fuel source,” says Marion Nestle, a professor of nutrition at New York University. “It’s only excess sugar intake that causes problems,” because the hormones that maintain glucose levels can’t handle large amounts without being secreted excessively, which disrupts metabolism.

Too much sugar can raise disease risk through weight gain, inflammation, and insulin resistance. That’s why health experts often encourage cutting back—and why so many people turn to substitutes. But researchers are learning that these substitutes are “not inert,” says Susie Swithers, a professor of behavioral neuroscience at Purdue University. “They don’t just wash through us.”

Sweeteners can change more than taste. Evidence suggests they can affect weight, gut microbiome, and metabolism. The catch: it’s hard to pin down which sweetener does what. Many studies group them together or mix healthy people and those with chronic conditions, as well as longtime sweetener users with those who’ve barely had any, says Yanina Pepino, a nutrition professor at the University of Illinois Urbana-Champaign.

So, we broke them apart. Here’s how four of the most common sugar substitutes move through the body—and what that could mean for your health.

Aspartame

First approved by the U.S. Food and Drug Administration in 1981, aspartame is a synthetic compound made by linking two amino acids—phenylalanine and aspartic acid—with methyl ester. It’s about 200 times sweeter than sugar, so only a tiny amount is needed. You’ll find it under brand names like NutraSweet or Equal, in everything from diet sodas to sugar-free gum.

Once consumed, aspartame is broken down in the small intestine into its building blocks. Because it’s fully digested before reaching the colon, scientists generally don’t expect effects on the gut microbiota, though some studies have reported subtle shifts.

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In the short term, aspartame doesn’t seem to affect body weight, unlike ordinary sugar, which led to weight gain in a 12-week trial comparing sweeteners. It also produces smaller blood-sugar spikes after meals. But when stacked against other sweeteners—or even plain water—the differences are minimal. Some studies even suggest it may trigger more hunger than its rivals.

Animal studies have found that high doses can increase insulin secretion and worsen atherosclerosis—the fatty deposits in arteries. But studies on mice often use larger amounts than usual, says Graham Finlayson, a professor of psychobiology at the University of Leeds. “You have to be really careful trying to extrapolate that to people.”

Large observational studies, tracking cohorts over several decades, have linked higher intakes of aspartame to greater body weight and fat, or increased risks of certain cancers. Those findings led the International Agency for Research on Cancer to classify aspartame as “possibly carcinogenic,” though other regulators have kept intake limits unchanged.

Sucralose

Sold under the brand name Splenda, sucralose hit U.S. shelves in the 1990s, and at the time, it most closely resembled the taste of sugar compared to other sweeteners, says Pepino.. It is made by chemically altering sucrose by swapping out three hydroxyl groups for chlorine atoms. That transformation makes it roughly 600 times sweeter than sugar and also makes it resistant to digestion—meaning most of it passes through the gut and is excreted in poop.

Some trials in healthy adults show that sucralose doesn’t affect glucose and hormone responses when it’s consumed before carbohydrate intake. But other research has found the opposite, showing it can impair healthy people’s ability to manage glucose.

“People with obesity may be more sensitive to some of these effects,” says Pepino, because their metabolism is already misaligned. In one trial, people with obesity who had sucralose before a glucose test showed slightly higher blood sugar, greater insulin release, and reduced insulin sensitivity compared to when they did the test without having the sucralose.

In one 12-week trial, people who consumed sucralose ate fewer calories, reported eating less often, and saw a slight drop in weight compared to those given aspartame or other sweeteners. But some evidence has found that sucralose increases blood flow in the hypothalamus, which might affect appetite control.

Stevia

Derived from a South American plant, stevia is often seen as a “natural” alternative to lab-made sweeteners—but that doesn’t make it automatically better, says Swithers. Stevia’s sweetness comes from compounds called steviol glucosides, which are extracted and concentrated to create a product about 300 times sweeter than sugar.

Unlike aspartame or sucralose, stevia reaches the colon intact, where gut bacteria break it down into steviol. This compound is then absorbed and processed by the liver until it’s ultimately excreted in urine. Some studies suggest this process could benefit the gut microbiome, though others have found little effect.

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When used in place of sugar, stevia lowers glucose and insulin responses to food, particularly in people with obesity. In one study, snacks sweetened with either aspartame or stevia reduced daily calorie intake, and stevia also blunted the blood sugar and insulin spikes after the meal. Another found that people consuming stevia maintained their weight, while a control group gained. The reason isn’t entirely clear, since other research shows it doesn’t affect appetite.

Not all forms of stevia are approved worldwide. In the U.S. and European Union, purified steviol glycosides are allowed, but whole-leaf stevia and crude extracts remain unapproved due to insufficient safety data.

Monk fruit

Like stevia, monk fruit is marketed as a “natural” sweetener—this one derived from a small fruit native to Southeast Asia. Its sweetness comes from a compound called mogroside V, which is roughly 200 times sweeter than sugar. The FDA granted various forms of monk fruit extract “generally recognized as safe” status since 2010; it now shows up in a variety of pantry foods, including chocolates, cereals, and beverages.

Because it’s relatively new, human studies on monk fruit are limited. A small trial comparing monk fruit and other sweeteners with sucrose found almost no difference between the no-calorie sweeteners in daily energy intake, post-meal glucose levels, or insulin responses. There was no difference between ordinary sugar and monk fruit in a 24-hour glucose monitoring study. In fact, whether the sweetness came from an artificial compound or a natural one didn’t change the results.

Animal research suggests possible metabolic and health benefits. Some studies indicate that mogroside extracts may improve fasting glucose and insulin sensitivity, while others report anti-inflammatory effects or even the potential to inhibit cancer cell growth. But so far, those effects haven’t been confirmed in people.

Are artificial sweeteners healthier than sugar?

Sweeteners—natural or artificial—all share the property of tasting sweet, says Pepino, which could potentially activate sweet taste receptors. And those receptors aren’t just on the tongue—they’re scattered throughout the body, influencing metabolism, appetite, and insulin responses, Swithers explains.

(Should we switch to eating more sugar?)

Still, the science isn’t settled on exactly whether specific sweeteners are harmful, harmless, or even helpful. For those trying to swap out sugar in their diet, there’s evidence that it can be beneficial, especially for chronic conditions like type 2 diabetes.

But the bigger lesson may be simpler: aim for less sweetness overall. “It doesn’t matter if it’s with sugars or with some artificial sweeteners,” says Pepino. But acknowledge that these chemicals are not inert, sweetness has physiological effects, she says.