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Recent research has painted a pretty bleak picture for sugar-lovers, linking excessive sugar consumption to obesity, diabetes, and heart disease. So you might be tempted to switch to artificial sweeteners or any of the myriad of high-intensity sweeteners available today.

At first glance, that seems like it would let you have your cake and eat it too, giving you the sweetness of sugar without so many calories. And that’s about where things were in 2013, when we talked about sweeteners in our episode on “The Science of Sweetness.” But since then, scientists have been hard at work studying the potential impacts of switching from sugar to things like Sweet ‘n Low or Splenda— and a fierce debate about the effects of sweeteners has emerged. One thing seems certain, though: they aren’t going to fix all the things sugar broke.

Several large epidemiological studies in humans—some containing nearly half a million participants—have basically eliminated fears raised in the 1970s that artificial sweeteners like saccharin cause cancer. But in the past couple decades, studies have started to suggest that they and other high-intensity sweeteners might still have negative effects on the body. Some of the strongest evidence against these sweeteners centers around the idea that they help with weight loss.

They’re used in things like diet sodas or low-calorie snacks because they can replace sugar’s sweetness with way fewer calories. Some, like the steviol glycosides found in the natural sweetener Stevia, aren’t processed in our guts the same way as sugars, so they don’t have any calories of their own. And even those that do are tens to thousands of times sweeter than sugar, so they can be used to make low-calorie substitutes for our favorite sweets.

But in 2014, a large meta-analysis of randomized controlled trials—the gold standard for health research—found that using artificial sweeteners instead of sugar resulted in weight loss of just 0.8 kg on average. And individual results in studies vary from tons of weight loss to weight gain. The lack of a clear weight-loss benefit might come down to what sweetness does to mammal brains.

Normally, a sweet taste means that the body receives a bunch of calories—the food energy we need to survive. So some scientists think tasting sweetness without getting an energy boost confuses the parts of the brain that regulate hunger and fullness. This confusion could mean we don’t know when to stop eating, so we actually end up eating more overall.

Though this phenomenon hasn’t been conclusively demonstrated in people, studies in animals suggest it can happen. In one study, rats fed sugary food ate much less of a sweet yogurt when offered it than rats only fed saccharin-sweetened food before. And there might be other factors at play as well that explain why lowering sweet calories doesn’t translate into weight loss.

We used to think that because high-intensity sweeteners aren’t digested like sugars, they just pass through our guts unnoticed. But several recent studies in rodent models have suggested that they can affect intestinal bacteria, which play a big role in how we process food. For example, a paper published in Nature in 2014 found that mice fed saccharin developed changes in their gut microbiome and symptoms of prediabetes.

Scientists then transferred gut bacteria from these mice into germ-free mice—animals that are born by Caesarean section and raised in totally sterile conditions. And those mice also developed prediabetes symptoms, which is strong evidence that sweetener-induced changes to the microbes were to blame. But similar studies haven’t been conducted on people, and I know we say this a lot, but it’s worth repeating: rats aren’t people.

In fact, that’s a common theme in sweetener research. Since, for ethical reasons, most studies on humans are observational, it’s difficult to determine cause and effect. And studies finding strong negative effects on sweeteners in animal models have created a rift of sorts in the scientific community.

One camp thinks that sweeteners actually cause harm, and that the animal studies show us what’s really going on. They point to observational studies in humans as further proof— like a 2017 study of over 64,000 women which found that heavy consumers of any type of artificial sweetener were about 21% more likely to develop type 2 diabetes. The other camp says the the rodent studies aren’t realistic—the rodents are fed way too much of a sweetener, for example—and so those researchers think something else explains human study findings: reverse causation.

As the name implies, that’s when two observed things are indeed correlated, but the cause and effect are flipped from what you think. In other words: yes, sweetener consumption is linked to diabetes, but not because the sweeteners are causing diabetes. Instead, it could be people knowing they have a higher risk for diabetes that drives their sweetener use.

And that’s what scientists in a 2011 study of more than 40,000 men concluded. While there was an irrefutable link between sugary drinks and type 2 diabetes in their data, the link between diet drinks and diabetes disappeared when they corrected for other potential factors like the participants’ starting weight. The scientists in the 2017 study of women did similar statistical analyses to control for BMI and several other major risk factors for diabetes—and the connection between sweeteners and diabetes remained significant.

But the statistics are very complicated, and many scientists, including those involved in the 2017 study, argue the math isn’t always able to completely remove the influence of other risk factors, a concept known as residual confounding. For example, it’s possible the significant increase in diabetes risk from sweetened drinks in the 2017 study was driven by participants that were obese at the beginning of the study. Because of the difficulties of conducting nutritional science in people, the scientific debate about high-intensity sweeteners isn’t going to be resolved any time soon.

But there is something everyone seems to agree on, and that’s that high-intensity sweeteners aren’t a magic bullet. So if you really want to improve your overall health, you might want to limit both sugar and sweeteners in your diet. Thanks for watching this episode of SciShow.

If you want to learn more about why people like sugar and how all these different sweeteners work, you might want to check out that video I mentioned called The Science of Sweetness. [OUTRO ♪].