Food and Behaviour Research

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The Small Intestine Converts Dietary Fructose into glucose and organic acids

Jang C, Hui S, Lu W, Cowan AJ, Morscher RJ, Lee G, Liu W, Tesz GJ, Birnbaum MJ, Rabinowitz JD (2018) Cell Metab Feb 2018; 27, 2: 351–361.e3, 

Web URL: Read the research on here


Excessive consumption of sweets is a risk factor for metabolic syndrome. A major chemical feature of sweets is fructose.

Despite strong ties between fructose and disease, the metabolic fate of fructose in mammals remains incompletely understood. Here we use isotope tracing and mass spectrometry to track the fate of glucose and fructose carbons 
in vivo, finding that dietary fructose is cleared by the small intestine. Clearance requires the fructose-phosphorylating enzyme ketohexokinase.

Low doses of fructose are ∼90% cleared by the intestine, with only trace fructose but extensive fructose-derived glucose, lactate, and glycerate found in the portal blood.

High doses of fructose (≥1 g/kg) overwhelm intestinal fructose absorption and clearance, resulting in fructose reaching both the liver and colonic microbiota. Intestinal fructose clearance is augmented both by prior exposure to fructose and by feeding.

We propose that the small intestine shields the liver from otherwise toxic fructose exposure.


It has long been known that high intakes of the simple sugar fructose have more damaging effects on health than glucose - leading to fatty liver disease, obesity, Type 2 diabetes and other metabolic conditions.  

Fructose is found naturally only in fruits and sweet vegetables. However, compared with any type of traditional, pre-industrial diet, modern, western-type diets provide very high intakes - as fructose makes up 50% of table sugar (the rest of which is glucose), and a fairly similar proportion of high fructose corn syrup - both of which are used extensively in ultra-processed foods and drinks.

This study shows that while small amounts of fructose are absorbed via the small intestine, larger amounts overwhelm this system, and as a result, excess fructose is either diverted to the liver (which converts it to fat) or passes through to the large intestine, where it can disrupt normal gut microbial balance.

These findings are important, as they help to explain why fructose - when consumed in more than the small quantities found naturally in fruits and some vegetables - is linked with both physical and mental health disorders via these toxic effects on the liver and the gut microbiome.  

See the associated news article and FAB comment, which give further details of the practical implications of these findings:

And for further information on how sugar affects gut health, please see the following lists, which are regularly updated.