- Nonalcoholic steatohepatitis (NASH) is an aggressive form of fatty liver disease that can cause severe liver damage and greatly impact overall health.
- Currently, there are no effective treatments for NASH, but a recent study found that vitamin B12 and folate could 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 to counteract underlying mechanisms.
Liver problems can occur for a variety of reasons but are not always caused by alcohol consumption.
Nonalcoholic fatty liver disease (NAFLD) is a term that describes a range of conditions caused by a buildup of fat in the liver. Unrelated to alcohol consumption, NAFLD is caused by other factors and commonly leads to inflammation and liver damage.
In more severe or aggressive cases, NAFLD may be diagnosed as nonalcoholic steatohepatitis (NASH).
Currently, there are no medications that can treat nonalcoholic steatohepatitis. But a recent study published in the Journal of Hepatology examined the mechanisms of NASH and discovered that a specific protein, syntaxin 17, was prevented from doing its job of removing dead and unhealthy cells.
What’s more, researchers found that vitamin B12 and folate worked to increase the levels of syntaxin 17 and helped reverse the fibrosis (thickening or scarring) and inflammation of the liver.
Impact of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
The National Institute of Diabetes and Digestive Kidney Diseases (NIDDK) identifies fat buildup in the liver as a defining characteristic of nonalcoholic fatty liver disease (NAFLD).
Certain health conditions increase a person’s risk of developing NAFLD, such as:
- overweight and obesity
- type 2 diabetes
- insulin resistance
- metabolic syndrome
- high blood pressure
- high cholesterol
Some people with NAFLD can further develop liver damage and inflammation, leading to nonalcoholic steatohepatitis (NASH).
NASH can cause scarring and permanent liver damage, increasing the risk for liver cancer. Currently, there are no medications that can effectively treat NASH.
Dr. Jude Oben, a consultant 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 condition that affects about 25% of the global population. It is mostly associated with obesity. Its more severe stage, nonalcoholic fatty steatohepatitis (NASH) afflicts about 5% of the global population. NASH may lead to liver cirrhosis, a 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 to counteract the underlying mechanisms.
B vitamins reverse liver inflammation and fibrosis in NASH
The current study’s authors examined the actions that occur in the development of NASH utilizing human subjects, mouse models, and primates. They found that increases in the amino acid homocysteine (Hcy) were present at the same time as hepatic inflammation and fibrosis.
They also found that high levels of homocysteine in the liver induced and worsened NASH. Homocysteine further impacted a specific protein, syntaxin 17, which is critical for removing damaged cells from the body, a process called autophagy.
Researchers used mice and cell cultures to examine how vitamin B12 and folate could help.
They found that vitamin B12 and folate helped to restore the expression of syntaxin 17 and the autophagy process. Ultimately, vitamin B12 and folate helped to reduce NASH inflammation and fibrosis.
Dr. Oben was interested in the information this study provided about 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) brings a novel view to these diseases. Using non-human models, they showed clearly 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 pathway. Homocysteine appears to be raised in NASH with its metabolism reduced in NASH…” – Dr. Oben, study author
Study author Dr. Paul M. Yen, professor of medicine and member of the Duke Molecular Physiology Institute in Durham, North Carolina, explained to MNT:
“…Remarkably, we found vitamin therapy could prevent and reverse fat accumulation, inflammation, and fibrosis in two different mouse models of NASH. Our preclinical findings suggest that vitamin therapy could be a first-line therapy, particularly in patients with low serum B12 and folate levels and elevated serum homocysteine levels.”
Areas for further research
The study provided excellent data in an area of research where there is limited information.
However, since much of the research involved mice models, further studies are needed to confirm the findings and to determine how best to treat people diagnosed with NASH.
Researchers suggest that vitamin B12 and folate might be useful, particularly as a preventive treatment or first-line therapy for NASH.
Further clinical studies can look at how vitamin B12 and folate can help people with NASH. Dr. Yen explained to MNT:
“Our preclinical studies suggest that NASH patients who have pernicious anaemia, gastritis, prior gastric bypass surgery, diabetes and taking metformin, or are vegetarians with low folate/B12 intake are several populations that may be at potential risk for worsened NASH. They most likely should be screened for serum B12, folate, and homocysteine levels since they could benefit from vitamin B12 and folate therapy. Further clinical studies need to be performed to confirm whether vitamin therapy improves NASH in these patients.” – Dr. Paul M. Yen, study author
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