Trehalose to treat fatty liver?

A new study in mice suggests that the sugar trehalose could be useful in reversing obesity-associated, nonalcoholic fatty liver disease as it stimulates liver cells into autophagy (self eating) and so cleans them up of the problematic excess fat. The accumulation of lipids (fats) in hepatocytes (liver cells) that occurs in NAFLD can lead to liver failure or liver cancer, so it sounds like a good thing to find a simple compound readily available in lots of foods that might reverse the harm.

“In general, if you feed a mouse a high-sugar diet, it gets a fatty liver,” explains DeBosch. “We found that if you feed a mouse a diet high in fructose plus provide drinking water that contains three percent trehalose, you completely block the development of a fatty liver. Those mice also had lower body weights at the end of the study and lower levels of circulating cholesterol, fatty acids and triglycerides.”


So, where can you get plenty of trehalose in your diet? Well, trehalose is essentially two glucose molecules stuck together, a disaccharide, joined by a glucoside bond, which will presumably be broken by digestive enzymes releasing nothing more than glucose. It’s present in ergot of rye (a mould) and in so-called trehala manna made by weevils. It’s also the sugar in bee and butterfly blood (also found in the marginally more palatable grasshoppers and locusts and is thought to be the chemical responsible for allowing dessicated tardigrades (water bears) to spring back into life when immersed in water). It’s also found in shrimp and shiitake (Lentinula edodes, which similarly spring back into shape when water is added) mushrooms (also in oyster, king oyster, golden needle, maitake (Grifola fondosa), nameko (Pholiota nameko), and Judas’s ear (Auricularia auricula-judae). (I feel a stir-fry coming on). Trehalose is also present in yeast (both wine and baker’s). It is also present in sunflower seeds, moonwort, Selaginella plants and marine algae.

There was earlier research that suggested the autophagy triggered by trehalose might lead to a reduction in the damaged, misfolded proteins that accumulate in the brain in Parkinson’s disease and Huntington’s disease and tauopathies, such as Alzheimer’s disease. I wouldn’t be surprised therefore if there aren’t companies already flogging trehaolose as some kind of elixir of youth. Indeed, in the paper cited below, author Brian DeBosch of Washington University at St Louis (WUSTL) and colleagues say that trehalose:

may be a 'silver bullet' for treating diseases resulting from inadequate cellular degradative metabolism.

Trehalose inhibits solute carrier 2A (SLC2A) proteins to induce autophagy and prevent hepatic steatosis,  Brian J. DeBosch, Monique R. Heitmeier, Allyson L. Mayer, Cassandra B. Higgins, Jan R. Crowley, Thomas E. Kraft, Maggie Chi, Elizabeth P. Newberry, Zhouji Chen, Brian N. Finck, Nicholas O. Davidson, Kevin E. Yarasheski, Paul W. Hruz, and Kelle H. Moley, Sci. Signal. 2016, 9, ra21 DOI: 10.1126/scisignal.aac5472

Technical details from the paper offer an explanation as to mode of action of trehalose in reversing NAFLD:

“trehalose inhibited members of the SLC2A (also known as GLUT) family of glucose transporters. Trehalose-mediated inhibition of glucose transport induced autophagy and regression of hepatic steatosis in vivo and a reduction in the accumulation of lipid droplets in primary murine hepatocyte cultures.”

However, there are at least two enzymes, trehalase in the intestine and threhalase in the liver, that break down trehalose to glucose, so eating it neat is, one would think, unlikely to have any therapeutic effect. But…I asked De Bosch about this and confessed that they simply “don’t know yet!” adding that the necessary research is under way. “We do measure it [by mass spectrometry] at 1-5 micromolar in the peripheral blood after it escapes intestinal and portal circulation!” he told me.

Of course, before you go rushing out to find that trehalose supplement, remember this trial was done only in mice, we don’t yet know whether it will reverse fatty liver in people, how much would be needed to do so and whether or not there are side effects of dosing up on this sugar. However, there’s nothing stopping you from increasing your intake of arthropods and fungi. Indeed, here’s a nice recipe for stir-fried prawns and shiitake mushrooms and I’m sure you could substitute locusts for those prawns if you wanted to.