Researchers in America say artificial sweeteners make it harder for people to regulate their intake of food and may therefore lead to overeating.
The findings come from Purdue University, Indiana, where rats given low-calorie yogurt gained more weight and body fat than those given a sugary version.
Susan Swithers and Terry Davidson, who wrote the study, said the results may explain why obesity levels and the use of artificial sweeteners have risen simultaneously.
They said sweet foods provide an "orosensory stimulus" which tells the body that a lot of calories are about to be consumed.
When that does not happen, the body becomes confused, leading people to eat more to compensate for the food's low calorie content.
"Digestive reflexes gear up for that intake, but when false sweetness isn't followed by lots of calories, the system gets confused," they said. "Thus, people may eat more or expend less energy than they otherwise would."
The findings will be a blow to the millions who use low-calorie artificial sweeteners to help them lose weight.
In America, the number of people who eat foods containing sugar-free sweeteners has doubled from 20 years ago to about 160 million. Changing lifestyles mean that more Britons are also opting for low-calorie drinks. According to the British Soft Drinks Association, they now command 61% of the market.
The study, published in the Behavioral Neuroscience journal, follows research last year which said that giving children low-calorie food and diet drinks may increase their risk of becoming obese.
A team of researchers in Canada suggested that children may just eat more to compensate for the lack of calories. The scientists concluded that it was better for children to eat healthy, well-balanced diets with sufficient calories for their daily activities rather than low-calorie snacks or meals.
Carina Norris, a registered nutritionist and author of You Are What You Eat: Total Health Overhaul, said she would encourage people to wean themselves off artificial sweeteners. "They can be useful as part of a calorie controlled diet, but people tend to rely on them too much, even though they do not address the root cause, which is that a person has a sweet tooth.
"People who are keen to shed pounds should try to retrain their palate so that they enjoy foods without a lot of sugar. That's not easy, of course, but is possible."
From the February 18, 2008, Prepared Foods e-Flash