Trehalose Sugar May Treat Fatty Liver Disease

Image: Wikipedia

Trehalose, a natural sugar prevents fatty liver disease in mice, suggests a new study. Researchers discovered that trehalose prevents the sugar fructose -- thought to be a major contributor to nonalcoholic fatty liver disease.


First author Brian J. DeBosch, MD, PhD, a pediatric gastroenterologist from St. Louis Children's Hospital in Missouri said:

"In general, if you feed a mouse a high-sugar diet, it gets a fatty liver.”

"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."


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When ingested, trehalose enters the liver and triggers a cellular housekeeping process that cleans up excess fat buildup inside liver cells, said the researchers at Washington University School of Medicine in St. Louis.

Nonalcoholic fatty liver disease (NAFLD) occurs when fat is deposited (steatosis) in the liver due to causes other than excessive alcohol use. In developed countries, it is the most common liver disorder. A recent study using the National Health and Nutrition Examination Survey (NHANES) found a 30% prevalence of NAFLD in the United States between 2011 and 2012.

Fructose is thought to be a majorcontributor to the disease. Corn syrup, used in soft drinks and many processed foods is high in fructose. Studies have shown that NAFLD develops as the liver strives to process dietary sugar.

There is no drug treatment for the disease, although weight loss can reduce the buildup of fat in the liver.

Excess fructose is stored in the liver as triglycerides, a kind of fat that can ultimately reach toxic levels, potentially necessitating a liver transplant.


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Trehalose is a natural sugar found in plants and insects and consists of two glucose molecules bound together. While it is approved by the Food and Drug Administration (FDA) for human consumption, DeBosch cautions that more research is required before trehalose could be tested in people with NAFLD as part of a clinical trial.

Dr. DeBosch and colleagues previously discovered that GLUT8, a protein on the surface of liver cells, is needed for mice to develop fatty livers in response to a high-fructose diet.

"We knew that GLUT8 carries large amounts of fructose into liver cells," DeBosch said.

"So we looked for things that block GLUT8. We were interested in investigating trehalose because it has been studied in models of neurodegenerative disorders such as prion disease or amyotrophic lateral sclerosis -- Lou Gehrig's disease. In mice, trehalose appears to cause brain cells to swallow up abnormal proteins that accumulate in these conditions. We wondered if it would do the same for fat buildup in liver cells."


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To examine this further, they fed mice a high-fructose diet plus drinking water that contained 3% trehalose.

DeBosch and his colleagues found evidence that trehalose blocks the transport of energy in the form of sugar into liver cells, causing the cells to behave as if they're starving.

At the end of the study, the mice had a lower body weight, and the circulating levels of cholesterol, fatty acids and triglycerides had fallen.


When a cell is in a state of starvation, it triggers a process called autophagy, or self-eating. Researchers describe autophagy as a kind of "house-cleaning" process, which may occur in response to the stress of too much fat or protein buildup, or a lack of energy. This process begins to consume the fat already stored in the cell. 

Human liver (Image: Pixabay)

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Dr. DeBosch believes this treatment strategy could have potential beyond neurodegenerative and metabolic diseases, and he expects that other researchers may turn their attention to trehalose in order to understand exactly how this sugar hijacks cell signaling pathways.

He explained:

"Autophagy plays numerous roles in the body, ranging from healthy development to involvement in cancer and autoimmunity. The hope is that by studying this 'nutraceutical' and its actions, we can uncover and then leverage its important cellular activities to halt or reverse disease."

But the process is not specific to fat and can drain cells of proteins, sugars and other waste.

Dr. DeBosch cautioned:

"I can't recommend it to my patients yet. We know the mice that received drinking water with 3% trehalose lost weight, and we suspect that weight loss was due to loss of fat, but we can't be certain that's the only effect. We need more studies to make sure they were not losing bone or muscle mass."


The researchers emphasized the need for more research prior to carrying out clinical trials of trehalose in people with NAFLD.

In the meantime, DeBosch advises his patients to avoid foods with added fructose, especially sugar-sweetened beverages.

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The study was published in the journal Science Signaling.


NAFLD at a glance

• When the liver contains 5-10% or more fat it is described as "fatty liver"
• Not only obesity and diabetes, but rapid weight loss and poor diet can also cause NAFLD
• NAFLD can cause swollen liver, liver cancer and liver failure.
• It is very common and increasing in prevalence.
• Symptoms can be fatigue, weight loss, general weakness and an ache in the upper right part of the belly.
• Fatty liver is also associated with type II diabetes, obesity, and high triglyceride levels in the blood, celiac disease, and Wilson's disease (abnormality of copper metabolism).

·         There is no drug treatment for the disease, although weight loss can reduce the buildup of fat in the liver.