The small intestine, not the liver, is the first stop for processing fructose

When it comes to processing fructose, the liver is a pinch hitter for the small intestine.

To use fructose for energy, the body needs to convert it into another type of simple sugar called glucose or into other smaller molecules. Scientists knew fructose could be metabolized in both the liver and the small intestine, but believed the liver was mainly responsible for the process. A new study in mice suggests otherwise, showing that moderate doses of fructose — a sugar found in honey and fruit as well as such corn syrup‒sweetened products as soda — are transformed in the small intestine. The liver steps in only when the small intestine gets inundated, researchers report February 6 in Cell Metabolism.

In that way, the small intestine shields the liver from dangerously high doses of fructose, says Joshua Rabinowitz, a metabolism researcher at Princeton University. In humans, too much fructose puts the liver at risk for conditions such as fatty liver disease, and raises the overall risk of obesity and type 2 diabetes (SN: 10/5/13, p. 18).  

But how much fructose is too much is still up in the air (SN Online: 5/26/15). Rabinowitz and colleagues fed mice a mixture of equal parts glucose and fructose (the ratio in basic table sugar), in which certain carbon atoms had been swapped out for a slightly heavier form of carbon. That allowed researchers to track which sugars were being transformed and where their by-products, or metabolites, were ending up. The researchers collected samples from different mouse organs, and identified the molecules with heavier carbon when separating out the metabolites by weight.

At lower sugar doses, researchers found metabolites from labeled fructose molecules abundant in the small intestine, and only small amounts in the liver and in the vein that connects the small intestine to the liver. Lots of glucose molecules were found in this vein, though, with labels showing some had been chemically transformed from fructose molecules in the small intestine. 

At high sugar doses, the small intestine couldn’t keep up: The vein connecting the intestine and liver had a much higher ratio of fructose to glucose than at lower sugar doses. That suggests the small intestine was passing some fructose along to the liver.

The study’s focus on how the body handles fructose at different doses shows the workload breakdown between the two organs and suggests a protective role for the small intestine, says Gilles Mithieux, a nutrition researcher at the French National Institute of Health and Medical Research in Lyon who wasn’t part of the study.

But translating these findings into dietary recommendations for people could be challenging, cautions  Luc Tappy, a physiologist at the University of Lausanne in Switzerland who wasn’t part of the study. It’s hard to compare sugar doses between humans and mice, which expend more energy relative to body weight than humans. So scaling up the dose of sugar by body weight would be “meaningless,” he says.  

Scaling up by the animal’s body surface area — another common way of comparing doses between species — might be more appropriate, he says. By that measure, the regular dose given to mice in the study corresponds to about 5 grams of sugar for people — about as much as is found in a quarter of an apple. Most people probably eat much more than that in a day, Tappy says.

Plus, scientists don’t know whether the small intestine is a safer place to process fructose than the liver, Rabinowitz says. His lab plans to research that next.

If these results do translate to humans, it could be good news. “This argues for sweets in moderation being okay,” Rabinowitz says. So keep eating apples, but maybe cut back on the Big Gulps.