Researchers have claimed that our brains can distinguish real from fake, when it comes to calorie-free artificial sugars claiming to be as sweet as actual sugar.
Saccharin, the first of the industrially manufactured artificial sweeteners, was discovered late in the 19th century and soon became popular.
Since then, a parade of sweeteners has come on stream, including cyclamate, aspartame, the sucrose-like (and very sweet) sucralose, and several others, including one called Rebiana, derived from a South American herb.
A handful of studies, starting in the 1980s, suggested that regular use of artificial sweeteners might even make people eat more, rather than less, by stimulating their appetites without satisfying them.
And recently, Guido Frank, a psychiatrist at the University of Colorado in Denver who has a particular interest in eating disorders, compared how the brain responds to sucralose and sucrose.
Thus, he fed the sweetener and the sugar to 12 women, adjusting the concentrations so that the sweetness of the two matched.
"They consciously could not distinguish them," New Scientist quoted Frank as saying.
But, when he looked at their brain responses with functional magnetic resonance imaging (fMRI), he saw clear differences.
Sucrose produced stronger activation in the "reward" areas of the brain that light up in response to pleasurable activities such as eating and drinking.
Sucralose didn't activate these areas as strongly, but it synchronised the activity in a whole constellation of taste-associated brain areas - and it did this more strongly than sucrose did.
Frank suggested that sucralose activates brain areas that register pleasant taste, but not strongly enough to cause satiation.
"That might drive you to eat something sweet or something calorific later on," he said.
Similar results emerged from brain-scanning experiments by Paul Smeets, a neuroscientist at Utrecht University Medical Center in the Netherlands, in which he fed volunteers two versions of an orangeade drink.
All these results suggest the brain has some way of detecting calories while food is still in the mouth.
While this discovery might seem like bad news for zero-calorie drinks, it could be the beginning of real progress in finding ways to help people reduce their calorie intake.