- Non-alcoholic steatohepatitis (NASH) is an aggressive form of fatty liver disease that can cause severe liver damage and have a significant impact on overall health.
- Currently, there is no effective treatment for NASH, but a recent study found that vitamin B12 and folate may help reduce inflammation and scarring in human subjects and animal models.
- Future studies are needed to better understand why NASH develops so that treatments can help counter the underlying mechanisms.
Liver problems can occur for a variety of reasons, but they are not always caused by drinking alcohol.
Non-alcoholic fatty liver disease (NAFLD) is a term that describes a range of conditions caused by an accumulation of fat in the liver. Unrelated to alcohol consumption, NAFLD is caused by other factors and usually results in inflammation and liver damage.
In more severe or aggressive cases, NAFLD can be diagnosed as non-alcoholic steatohepatitis (NASH).
Currently, no drug can treat non-alcoholic steatohepatitis. But one recent study published in the Journal of Hepatology examined the mechanisms of NASH and discovered that a specific protein, syntaxin 17was prevented from doing its job of removing dead and unhealthy cells.
Additionally, researchers found that vitamin B12 and folate increased levels of syntaxin 17 and helped reverse fibrosis (thickening or scarring) and inflammation of the liver.
Some people with NAFLD may develop further liver damage and inflammation, leading to nonalcoholic steatohepatitis (NASH).
NASH can cause scarring and permanent liver damage, increasing the risk of liver cancer. Currently, no drug can effectively
Dr. Jude Obenconsultant gastroenterologist and hepatologist at Guy’s and St. Thomas’ NHS Foundation Trust in London, explained the following to MNT:
“Non-alcoholic fatty liver disease [NAFLD] is a disease that affects approximately 25% of the world’s population. It is mainly associated with obesity. Its most severe stage, non-alcoholic fatty steatohepatitis (NASH) affects approximately 5% of the world’s population. NASH can lead to cirrhosis of the liver, the need for liver transplantation and liver cancer. – Dr. Jude Oben, gastroenterologist and hepatologist
Further studies are needed to understand why NASH develops so that treatments can help counteract the underlying mechanisms.
The authors of the current study examined the actions that occur in the development of NASH using human subjects, mouse models and primates. They found that increases in the amino acid homocysteine (Hcy) were present alongside liver inflammation and fibrosis.
They also found that high levels of homocysteine in the liver induced and worsened NASH. Homocysteine also impacted a specific protein, Syntaxin 17, which is essential for removing damaged cells from the body, a process called autophagy.
The researchers used mice and cell cultures to examine how vitamin B12 and folate might help.
They found that vitamin B12 and folate helped restore syntaxin 17 expression and the autophagy process. Ultimately, vitamin B12 and folate helped reduce NASH inflammation and fibrosis.
Dr. Oben was interested in the information provided by this study on NASH and non-alcoholic fatty liver disease. He noted to MNT:
“…The detailed experimental paper just published by Tripathi and colleagues (Journal of Hepatology, July 2022) provides a new perspective on these diseases. Using non-human models, they clearly showed that vitamin B12 and folate reduced liver inflammation and liver scarring (fibrosis) in NASH. These agents appear to act by affecting the homocysteine pathway. This is not a well-studied path. Homocysteine appears to be elevated in NASH with its metabolism reduced in NASH…” – Dr. Oben, study author
Author of the study Dr. Paul M. Yenprofessor of medicine and fellow at the Duke Molecular Physiology Institute in Durham, North Carolina, told MNT:
“…Remarkably, we found that vitamin therapy could prevent and reverse fat accumulation, inflammation, and fibrosis in two different mouse models of NASH. Our preclinical results suggest that vitamin therapy could be a therapy for first line, especially in patients with low serum B12 and folate levels and high serum homocysteine levels.
The study provided excellent data in an area of research where information is limited.
However, since much of the research involved mouse models, more studies are needed to confirm the findings and determine how best to treat people with NASH.
The researchers suggest that vitamin B12 and folate could be useful, especially as a preventive treatment or as a first-line treatment for NASH.
Further clinical studies may examine how vitamin B12 and folate can help people with NASH. Dr Yen told MNT:
“Our preclinical studies suggest that patients with NASH who have pernicious anemia, gastritis, history of gastric bypass surgery, diabetes, and who are taking metformin, or who are vegetarians with low folate/B12 intake, are several populations at potential risk for worsening NASH and most likely should be screened for serum B12, folate and homocysteine levels as they may benefit from treatment with vitamin B12 and folate Further clinical studies are needed to confirm whether vitamin therapy improves NASH in these patients – Dr. Paul M. Yen, study author