Right now, there are limited pharmacological therapies available for people with nonalcoholic steatohepatitis (NASH). Rather, treatment options focus on healthy diet and exercise, weight loss, alcohol avoidance, lower cholesterol, and diabetes control. However, pharmacological therapies could help improve patient outcomes. Developing these therapies requires a deeper understanding of the underlying molecular mechanisms of NASH. According to an article published in Medical XPress, a Duke-NUS Medical School research and scientist team have not only identified a disrupted pathway that contributes to NASH, but a potential solution that could help treat patients.

The Research

So what exactly is this compound? It’s called spermidine. A research paper unrelated to this study explains that spermidine is: 

a polyamine present in our diet that is essential for the proper function of many metabolic processes…[and] also involved in most cellular functions, including the activation of autophagy, DNA stability, transcription, translation, and apoptosis. A part of the tissue polyamines has its origin in the diet or their production by the intestinal microbiome.

Foods with high spermidine content include certain types of mushrooms, soybeans, wheat germ, and pine nuts. 

Within this study, published in Nature Communications, researchers first began by evaluating liver enzymes in healthy individuals and individuals with nonalcoholic fatty liver disease (NAFLD). Next, the research team utilized preclinical NASH models to continue their work. Findings from the study include:

• The DOHH-EIF5AH pathway is disrupted in patients with NASH. This causes lower levels of an enzyme called deoxyhypusine hydroxylase (DOHH) in the body. Normally, this enzyme binds hypusine residue (created from spermidine) to a protein called EIF5A. 
• When the body does not have enough DOHH, and this process cannot occur, the pathway is disrupted. This leads to other issues, such as lowered fatty acid metabolism, mitochondrial activity, and protein synthesis within the mitochondria. 
• When spermidine was added to cell cultures, it improved fatty acid metabolism and mitochondrial function. Additionally, spermidine helped reduce fibrosis (scarring and scar tissue formation) and liver inflammation in models of nonalcoholic steatohepatitis. 

While these findings are promising, additional research is needed in the future to better understand this pathway and the potential use of spermidine as a therapeutic option for this patient population.

Nonalcoholic Steatohepatitis (NASH): An Overview

As the name suggests, nonalcoholic steatohepatitis is an advanced form of fatty liver disease that occurs in non-drinkers or people who drink very little. In NASH, fat accumulates in the liver, causing inflammation, scarring, and damage. This is a variable condition. Some individuals may not experience any symptoms, and in others, their condition also does not worsen. For others, NASH can cause liver dysfunction and failure. This condition affects up to 25% of people within the United States. Risk factors include type 2 diabetes, high cholesterol, metabolic syndrome, and obesity. Symptoms can, but do not always, include:

• Jaundice (yellowing of the skin, eyes, and mucous membranes)
• Nausea and vomiting
• Appetite loss
• Unintended weight loss
• Fatigue and general weakness
• Pruritus (intense itchiness)
• Abdominal pain
• Swelling of the lower extremities
• Confusion
• Spider-like blood vessels