A study which showed that rats fed on artificial sweetener still put on weight has baffled researchers.
Artificial sweeteners instead of sugar are widely used to lose weight
Scientists from Purdue University in the US now believe that a sweet taste followed by no calories may make the body crave extra food.
Their research, published in the journal Behavioral Neuroscience, found that rats fed sugar subsequently had lower appetites.
But nutritionists say that low-calorie sweeteners are still best for health.
Conventional wisdom says that, as part of a calorie controlled diet, artificial sweeteners can help people lose weight or keep it off.
But the Purdue study turns that wisdom on its head.
They gave different yoghurt to different groups of rats, some sweetened with sugar, and some with saccharin.
They were then given a plentiful supply of food, and the researchers observed the results.
The saccharin-fed mice ate more calories, put on more fat, and gained more weight than their sugar-fed counterparts.
They did not make any attempt to cut back on their food later to regulate their weight.
The researchers wrote in the journal: "The data clearly indicate that consuming a food sweetened with no-calorie saccharin can lead to greater body-weight gain and adiposity than would consuming the same food sweetened with higher calorie sugar."
One theory, they said, was that, in normal conditions, the arrival of a sweet taste in the mouth helped prime the metabolism for the arrival of a calorie-heavy, sweet meal into the digestive system.
When the meal does not arrive, they said, the body may get confused and have more trouble regulating its appetite when other food is around.
They said that if this were the case, other low-calorie sweeteners such as aspartame, sucralose and acesulfame could have a similar effect.
A spokesman for the British Nutrition Foundation, which receives funds from the food industry, said the study findings were "interesting", but did not prove that artificial sweeteners could be counterproductive in dieting humans.
"This needs far more research - as studies in humans have shown that low-calorie sweeteners can help people lose weight."