"Contains zero calories!" Countless soft drinks are emblazoned with that slogan as a come-on for those of us locked in a never-ending battle to rein in a spreading waistline. Calorie-free sweeteners certainly have a lot to offer. Food and drink manufacturers have become so good at blending sugar substitutes into their products that it can be almost impossible to tell them apart from the real thing - sucrose - in taste tests.
But while artificial sweeteners may be able to confuse our taste buds, the suspicion is growing that our brain is not so easily fooled. Could it be that our cravings for sugary foods run deeper than a liking for sweetness? If so, a whole bunch of weight-loss strategies may need rethinking. Non-sugar sweeteners have come a long way. One of the first, and perhaps the worst, was lead. Romans boiled grapes in lead pots, leaching the sweet-tasting metal into their food. The practice outlived the Roman empire by many centuries, and is thought to have led to the deaths of a number of notables, including Pope Clement II in 1047.
Saccharin, the first of the industrially manufactured artificial sweeteners, was discovered late in the 19th century and soon became popular. It does, however, have a potent aftertaste. Not for nothing has it earned itself a place in the English lexicon as the epitome of sickly sweetness. Since then, a parade of sweeteners has come on stream, including cyclamate, aspartame, the sucrose-like (and very sweet) sucralose, and several others.
Even as manufacturers get better at blending these agents to avoid peculiar tastes, their ability to help us cut down on calories and keep our weight in check is coming into question. A handful of studies, starting in the 1980s, suggest that regular use of artificial sweeteners might even make people eat more, rather than less, by stimulating their appetites without satisfying them. Though the methodology of some of these studies was questionable, the doubts continued.
More recently, the hunt has been joined by Guido Frank at the University of Colorado in Denver who has a particular interest in eating disorders. To compare how the brain responds to sucralose and sucrose, 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," Dr Frank said. Yet when he looked at their brain responses with functional magnetic resonance imaging, he saw clear differences. Dr Frank suggests 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.
A study that goes beyond brain mapping, published in July by Edward Chambers of the University of Birmingham, UK, adds weight to the idea that there is more to the appeal of sugary foods than sweetness. Chambers made eight cyclists perform 60-minute workouts on a stationary bike while measuring their work rate. A glucose mouth rinse improved the cyclists' performance by a small but consistent amount compared to saccharin.
The really surprising result came later, however, when Dr Chambers had the cyclists rinse their mouths with either saccharin alone or saccharin plus a calorific - but non-sweet - sugar called maltodextrin. The cyclists did slightly better when they rinsed their mouths with maltodextrin - even though both carried identical saccharin tastes. All these results suggest the brain has some way of detecting calories while food is still in the mouth. "It's an unconscious response," says Dr Chambers - and it is independent of sweetness perception. When Dr Chambers performed scans on his athletes, he got a glimpse of that unconscious response. The combination of saccharin and maltodextrin activated two reward-associated brain areas - the striatum and anterior cingulated - which saccharin alone failed to touch.
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. One approach focuses on information that has come in over the past decade describing the role of the receptor proteins on our taste buds. It is these receptors that detect the flavour molecules in our foods. While we seem to have about 30 different receptors for bitter tastes, there seems to be just one receptor for sweetness, formed by a pair of proteins called T1R2 and T1R3. It sits on taste buds near the tip of the tongue and, not surprisingly, binds to both sugars and artificial sweeteners.
These receptors have become the focus of efforts to create better sugar stand-ins - and could solve the problem of aftertaste that has long plagued artificial sweeteners - but they tell us little about the brain's apparent ability to discriminate between sugar and artificial sweeteners. Instead, it may be texture that is the key factor says Jayaram Chandrashekar, a neuroscientist at Howard Hughes Medical Institute in Janelia Farm, Virginia, who helped identify many taste receptors.
Because saccharin is several hundred times sweeter than sugar, Dr Chambers used far less of it - with the result that the glucose and maltodextrin drinks were more viscous than the saccharin-only drink. The brain may take these subtle texture cues into account, Dr Chandrashekar says. "When you eat something sweet you may activate two pathways, one for sweetness and one for texture," Dr Chandrashekar says. "Together they give you a better feeling than just the sweet pathway alone."
A non-calorific bulking agent to thicken up the zero-calorie drink might solve the problem. Such bulkers are already used in a variety of products, from smoothies to enchiladas. An alternative approach is under investigation at Senomyx in San Diego, California. The company has developed a tasteless molecule called S6973 that does not activate the sweet receptor directly, but changes it in a way that makes it bind more tightly to sucrose.
"This will cause the sugar molecule to stay on the receptor maybe two times as long," says Grant DuBois, a flavour chemist at The Coca-Cola Company in Atlanta, Georgia, which has financed research at Senomyx. "You can take a beverage that may normally contain 10 per cent sugar and make it with five per cent sugar, and it tastes the same." S6973 might still disappoint those of us who like to compensate for a million-calorie festive meal by drinking zero-calorie sodas - after all, drinks with sweetener enhancers will still contain as much as half the sugar of regular drinks. But that could actually be a plus if, unlike their zero-calorie cousins, these drinks manage to convince the brain that it is getting the calories it craves.
Nevermind the taste test; they might even pass the brain-scan test. @Email:www.newscientist.com