If you are using artificial sweeteners to control your weight, take heed. While past studies in both animals and humans have suggested they can lead to weight gain, scientists have identified how this can happen.

In a series of sophisticated lab experiments, scientists found that lab animals regularly fed a diet containing the popular artificial sweetener sucralose (Splenda) ate 30 percent more (yikes!) relative to when they consumed a naturally sweetened diet. The researchers directly related the boost in appetite and eating behavior observed in the lab mice fed the artificially sweetened chow to changes in an area of the brain’s reward center. This specialized area of the brain is responsible for integrating sweet taste and energy (calorie) density. From the beginning of time if we consumed a natural food, the sweeter the food the more calories it contained, and this important connection was duly registered in the area of the brain mentioned above.

But with zero calorie sugar substitutes, there is no relationship between sweet taste and calories, and this is where things get dicey. According to the researchers, what results is a recalibration in this special part of the brain that ultimately signals to the body that more calories are needed, thus boosting appetite and eating. As an additional consequence of this recalibration, sweetened foods taste even better, further promoting a sweet tooth and driving up excess calorie intake. Ironically, the neuronal pathway involved in this study’s findings is an ancient remnant from our early history that makes nutritious foods taste better when we are starving.

In addition to stimulating appetite, the researchers also noted that sucralose triggered hyperactivity, increased insomnia, and diminished sleep quality—all features common in a semi-starved state. I have never recommended the routine use of sugar substitutes for a host of reasons, and this report certainly adds to my list of concerns.

(Cell Metabolism, 2016; 24 (1): 75 DOI: 10.1016/j.cmet.2016.06.010)

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