Fructose may be the ultimate driver of obesity

Numerous hypotheses attempt to explain obesity‘s meteoric rise over the past few decades. There’s the energy balance hypothesis, which states that weight gain is due to consuming more calories than the amount expended. There’s the carbohydrate-insulin hypothesis, which argues that excess consumption of carbohydrates stimulates an insulin response that drives cells to accumulate fat. Then there’s the protein-leverage hypothesis, which suggests that we don’t eat enough protein, driving incessant hunger. Now, researchers have put forth a new hypothesis that places the blame on a sugar ubiquitous in modern food: fructose.

Commonly known as “fruit sugar,” fructose is a simple, monosaccharide sugar found in many plants. But the compound that sweetens your watermelon, apples, and oranges can mess with your cells’ energy metabolism, Richard Johnson, a professor of medicine at the University of Colorado, and his co-authors Laura G. Sánchez-Lozada and Miguel A. Lanaspa explain in a paper published October 17 in the journal Obesity.

“We suggest that obesity is not a disease of energy excess but rather a disease of energy crisis,” they wrote.

The fructose hypothesis

As studies in rodents have elucidated, fructose uniquely suppresses the function of mitochondria compared to other nutrients. When these cellular powerhouses are slowed, the cells get stuck in a low-energy state, triggering hunger and thirst. Eating nutrients including fats and protein eventually restores cellular energy levels, but not before we’ve eaten more calories than we need. This excess gets stored as fat.

In the long term, frequent fructose exposure can damage mitochondria and reduce the amount of mitochondria in cells, the researchers say, locking people in a low-energy state which drives chronic overeating.

High-fructose corn syrup in processed foods is a common source of fructose, but many other sugars such as honey and cane sugar also contain the compound. Due to our body’s metabolism, refined carbohydrates, salty foods, and alcohol (particularly beer) also generate fructose. As already mentioned, fruits contain fructose, but Johnson and his colleagues say that they are still quite healthy to eat. The amount of fructose inside whole fruits is far less than what is inside juices or candy. Moreover, the fibers present counteract fructose’s negative metabolic effects.

Obesity’s “theory of everything”

Like physicists attempting to combine general relativity and quantum mechanics with a “theory of everything,” the researchers behind the fructose-survival hypothesis say that it unifies the other obesity-explaining hypotheses rather than competes with them. Fructose’s energy-reducing effect underlies all of them.

With food in abundance, the metabolic changes driven by fructose result in obesity and poor health today, but they would have aided our survival in the deep past, when food was scarcer. For example, finding a fruit tree would likely have been a rare, fortuitous event for our ancestors. It would have been in their interest to eat as much as possible before the fruits fell off and rotted or were eaten by another animal. These calories could then be stored as fat to provide energy when food was not as plentiful.

But in much of the world today, food scarcity is not a problem, and fructose can be found in a great many of the things we eat, particularly those that are processed. So what can be done?

In a book published last year, Johnson recommended avoiding soft drinks, fruit juices, and other super sugary foods, watching salt intake, and limiting red meat and alcohol consumption, among other basic dietary tips. He also urged regular exercise as it stimulates mitochondrial activity and growth.

Johnson’s ultimate goal is to bring a drug that inhibits fructose metabolism to market. He’s working on formulating and testing one now, and hopes that his efforts will bear fruit in the next five years or so.