A recent study found that most dietary fructose is metabolized in the small intestine instead of the liver as previously understood. The study, performed in mice, also revealed that the small intestine becomes overwhelmed by large doses of fructose and that the excess spills over into the liver and into the colon. The study findings were published in Cell Metabolism.
Fructose is a sweet tasting hexose sugar with the same molecular formula (C6H12O6) as its non-sweet counterpart, glucose. High fructose consumption is known to be linked to metabolic disease with a strong correlation to obesity, non-alcoholic fatty liver disease, type 2 diabetes, kidney dysfunction, and cardiovascular disease.
Using isotope tracers and metabolomics, the researchers examined how much the different digestive organs—small intestine, liver and colon—contribute to sugar metabolism. Mice were given a fructose:glucose mixture which included a 13C label on one of the molecules and sugar metabolism was followed and analyzed by liquid chromatography mass spectrometry (LC-MS). The mice were also given labeled sucrose and labeled free fructose and similar metabolism experiments were performed.
The metabolism studies demonstrated that the small intestine can only process a limited amount of fructose and unabsorbed excess continues down to the colon where it encounters the large intestine’s natural microflora. The authors recommend further studies be performed to determine the impact of fructose on the microbiome.
"The microbiome is designed to never see sugar," Rabinowitz says. "One can eat an infinite amount of carbohydrates, and there will be nary a molecule of glucose that enters the microbiome. But as soon as you drink the soda or juice, the microbiome is seeing an extremely powerful nutrient that it was designed to never see."
The research also revealed that fructose is more quickly metabolized in the small intestine after eating a meal compared to a fasting state. The team observed that feeding the mice before fructose ingestion enhanced small intestine absorption. In a practical sense, eating a meal before having a sugary snack or drink may protect the liver and microbiome from the impact of fructose overflow.
Image: This graphical abstract depicts the findings of Jang et al., which show that it is actually the small intestine that clears most dietary fructose, and this is enhanced by feeding. High fructose doses spill over to the liver and to the colonic microbiota for metabolism, courtesy of Jang et al./Cell Metabolism 2018.