There is nothing new about controversy over artificial sweeteners. German research chemist Constantin Fahlberg discovered a calorie-free artificial sweetener in 1879 and called it “Saccharin.” The first commercial manufacture began in 1903 at the Hermes Company, and by 1906 it was already put on the defensive, with President Theodore Roosevelt coming staunchly to its defense: “Anybody who says saccharin is injurious to health is an idiot!”

A recent study by Dana Small, a neuroscientist at Yale University, has found evidence that artificial sweeteners do in fact come with inherent dangers, but in unexpected ways: rather than potential danger from carcinogens and other harmful chemicals, Small’s research indicates that the real danger is that of metabolic confusion – the body cannot metabolize properly when there is a mismatch between calories and taste, specifically sweetness. The study was published last Thursday in the journal Current Biology.

Like many discoveries, serendipity played a part in Small’s findings: her initial research was not about the metabolic effects of artificial sweeteners, but rather to answer the question of whether sweet foods are so appealing to humans because of their calorie content.

In her initial test, Small created five beverages, all tasting equally sweet – about as sweet as a beverage containing 75 calories of sugar. However, the calorie content of each drink varied, from 0 to 150 calories, including one beverage with 75 calories. After subjects consumed these drinks according to the experimental design schedule, Small checked to see how each drink affected the brain reward circuits, using fMRI brain scanning.

If her original prediction had been correct, then the more calories consumed, the greater the reward would be.

However, it turned out that the brain’s reward circuits were most active when subjects consumed the 75-calorie drink. This meant that the brain wasn’t happy simply when it got more calories – but it didn’t explain why one of the drinks that tasted the same as the others produced a stronger response in the reward circuitry.

Small worked on the problem with more experiments and analysis for two years before managing to make sense of these results. One experiment involved measuring the body’s metabolic response, in terms of how much energy it expended to process calories after consuming a low-, medium-, or high-calorie drink. One would expect more energy to be spent on the high-calorie drink, but stunningly, the response to the high-calorie drink was lower than it was for the medium-calorie drink.

Eventually, Small realized that taste signals the body how to respond to food. “It regulates the metabolic signal,” Small says.

The result was that when the sweet taste matched the calories, the experimental outcomes were as expected: the 75-calorie drink produced the greatest reward in the brain as well as the higher metabolic response. It is in the mismatch between taste and calories, that the reward, and more importantly, the metabolic response, was subdued. In this confusion, calories don’t get metabolized, and thus are probably stored in muscle, liver, or fat, all undesirable outcomes.

The findings have grave consequences for the food industry. “If sweeteners are disrupting how carbohydrates are being metabolized, then this could be an important mechanism behind the metabolic dysfunction we see in diets high in processed foods.” says Small. The results also suggest a context dependency – a diet drink by itself presents little harm, but when consumed with chips or other snack foods, the carbohydrates are not properly metabolized. Food companies may be undermining their customers’ efforts to lose weight when they produce products that blend sweeteners and carbohydrates.

“Taste,” Small says, “can change the metabolic fate of calories.”

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