Eventually, she pieced it all together. Sweetness, she realized, plays a role in how the body responds to food. "It regulates the metabolic signal," Small says.
When sweetness and calories were matched, it all ran as expected: the 75-calorie drink produced not only the largest metabolic response but also the largest brain response — because the calories matched the taste.
But when there was a "mismatch" between sweetness and calories, the response was strangely muted. "It's like the system threw up its hands and didn't know what to do," Small explains.
The findings present certain troubling questions. For example, what happens to all those "mismatched" calories that don't get metabolized? "We know it's not being used as a fuel" Small says. "What's happening to it?"
Those extra calories, she says, are probably being stored, either in muscle, in the liver, or in fat, none of which is desirable. "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."
The findings also suggest that whatever benefit or harm there may be to artificial sweeteners is context dependent. A diet drink consumed by itself and on an empty stomach may be far less harmful than one consumed with carbohydrates — with a sandwich, say, or a bag of chips.
But what's troubling is that in an effort to reduce added sugars, food companies are now designing all sorts of products that contain blends of sweeteners and carbohydrates that could be disrupting the body's metabolic response. The sports drink Powerade, Small notes in her paper, contains the sugars glucose and fructose alongside the artificial sweeteners sucralose and Acesulfame K. A yogurt product made by Chobani called Simply 100 similarly contains 14 grams of carbohydrate (six of which are from sugars) as well as stevia leaf extract.
This may also explain why the existing body of research on artificial sweeteners is so mixed. For example, a study published in The New England Journal of Medicinein 2012 found that Dutch children who consumed a single artificially sweetened beverage each day for 18 months gained less weight and less fat than children who drank a single sugar-sweetened beverage each day.
And yet, in much of the observational research — in which scientists look at large populations — people who consume artificially sweetened drinks, especially those who consume them a lot, appear to be at an alarmingly high risk for obesity, Type 2 diabetes, and cardiovascular disease.
Defenders of artificial sweeteners attribute this to "reverse causation." Obese people, they point out, are already at a higher risk for obesity and metabolic disease. And since obese people are likely to turn to artificial sweeteners to lose weight, these studies just make it appear as though the artificial sweeteners are putting them at higher risk. (These studies, in other words, can make correlations look like causes.) Critics of artificial sweeteners counter that they still look bad even when you adjust for BMI, and that rats fed artificial sweeteners have been found to gain more weight than rats who are not.
In the Dutch study, when the children consumed their beverages at school, it was during morning break. The paper does not indicate whether or not food was consumed alongside them, and if so what kind of food.
Small's research suggests this could be an important variable. Similarly, habitual users who drink, say, three or more artificially sweetened beverages a day may be more likely to consume them in combinations with food that are problematic.