Americans who think they are doing the healthy thing, as they pour no-calorie sweetener instead of sugar into their cup of morning coffee, may be fooling themselves, but they aren't fooling their brains, according to a recent Yale University study. Eating low-calorie sweetened foods can actually lead people to reach for higher calorie alternatives later on.

Over the last few years, many health professionals are discovering that the negative effects of artificial sweeteners are greater than had been previously thought. Artificial sweeteners reduce the body’s ability to regulate calorie intake, and in one study actually caused some human subjects to gain weight.

It seemed impossible. No one understood why a no-calorie sugar substitute could actually cause an increase in weight. A new study shows why this happens.

Neuroscientists at Yale's School of Medicine found that artificial sweeteners do not "fool" the brain into thinking its sugar. Instead, they leave the brain craving high-calorie foods even more.

In a series of experiments on mice, the scientists discovered a specific physiological brain signal that influences whether an animal prefers sugars to sweeteners. This signal controls the release of dopamine — “the reward chemical” — in an area of the brain called the dorsal striatum, the brain’s reward center.

To study the reinforcing effects of sugars vs. sweeteners, the scientists injected the mice with a drug that prevented the breakdown of sugars to glucose. This manipulation kept the mice from "using" the sugars that they consumed, and was accompanied by a reduction of dopamine release in the striatum.

When placed in front of a solution containing artificial sweetener, these "glucose-deprived" mice consumed less than half as much sweetener. And, instead, they significantly preferred another solution containing pure, glucose-containing sugar.

In a second study, the researchers kept mice hungry with a low-sugar diet (much as a dieter would be). These mice also dramatically preferred pure sugars over artificial sweetener, even though the sweetener tasted much sweeter than the pure sugar solution.

The studies showed that the consumption of artificial sweeteners causes a change in the brain (by reducing dopamine levels) that actually leaves it intensely craving real sugar.

According to the researchers, the results suggest that humans fed low-calorie foods during states of hunger or exhaustion might be more inclined to "relapse" and seek high calorie alternatives in the future.

This may lead some dieters to reconsider using artificial sweeteners in their morning coffee or cereals. Certain artificial sweeteners, such as Splenda®, have already been linked to increases in blood sugar levels and reduced insulin sensitivity.

In other words, artificial sweeteners are not the complete answer. But, then again, neither is sugar. So what is?

The scientists propose a solution: both sweeteners and pure sugar could be combined in precise quantities — so that overall glucose metabolism doesn’t drop but caloric intake is still kept to a minimum.

For now, that exact combination of sugar and sweetener still needs to be developed and tested in the lab before it becomes available for public consumption.

“We believe that the discovery is important because it shows how physiological states may impact on our choices between sugars and sweeteners,” Ivan de Arujo, associate professor of Psychiatry at Yale University School of Medicine and lead author of the study said in a statement.

This study is published online in the Journal of Physiology.