These findings research which was published in the Journal of Hepatology could help people with non-alcoholic fatty liver disease, an umbrella term for a range of liver conditions affecting people who drink little to no alcohol, which affects 25 percent of all adults globally, and four in 10 adults in Singapore.
A mechanism that causes an advanced form of fatty liver disease has been discovered by researchers at Duke-NUS Medical School in Singapore. It turns out that vitamin B12 and folic acid supplements can stop this mechanism.
Fat accumulation in the liver is a symptom of non-alcoholic fatty liver disease, which is the main reason for liver transplants globally. Due to its link to diabetes and obesity—two serious public health issues in Singapore and other developed nations—it has a high prevalence. Non-alcoholic steatohepatitis is the term used when the disorder proceeds to inflammation and the production of scar tissue (NASH).
“While fat deposition in the liver is reversible in its early stages, its progression to NASH causes liver dysfunction, cirrhosis and increases the risk for liver cancer,” said Dr. Madhulika Tripathi, first author of the study, who is a senior research fellow with the Laboratory of Hormonal Regulation at Duke-NUS’ Cardiovascular & Metabolic Programme.
NASH has no pharmaceutical therapy at this time since researchers don’t fully comprehend how the illness works.
The significance of homocysteine in the development of NASH remains unknown, despite the fact that it is known that the illness is linked to high blood levels of this amino acid. The relationship between homocysteine and the development of NASH in preclinical models and people was validated by Dr. Tripathi, research co-author Dr. Brijesh Singh, and their associates in Singapore, India, China, and the US.
Additionally, they discovered that as homocysteine concentrations in the liver rose, the amino acid linked to different liver proteins, altering their composition and impairing their functionality. In particular, homocysteine prevented a protein called syntaxin 17 from carrying and digesting fat in fatty acid metabolism, mitochondrial turnover, and the suppression of inflammation.
This caused NASH to develop and progress from fatty liver disease.
Importantly, the researchers discovered that adding vitamin B12 and folic acid to the preclinical models’ diets raised the levels of syntaxin 17 in the liver and restored its function in autophagy. Additionally, it stopped the progression of NASH and treated liver fibrosis and inflammation.
“Our findings are both exciting and important because they suggest that a relatively inexpensive therapy, vitamin B12, and folic acid, could be used to prevent and/or delay the progression of NASH,” said Dr. Singh. “Additionally, serum and hepatic homocysteine levels could serve as a biomarker for NASH severity.”
Professor Paul M. Yen, Head of the Laboratory of Hormonal Regulation at Duke-NUS’ Cardiovascular & Metabolic Disorders Programme, and senior author of the study, said, “The potential for using vitamin B12 and folate, which have high safety profiles and are designated as dietary supplements by the US Food and Drug Administration, as first-line therapies for the prevention and treatment of NASH could result in tremendous cost savings and reduce the health burden from NASH in both developed and developing countries.”
Professor Patrick Casey, Senior Vice-Dean for Research at Duke-NUS, said, “Currently, the only treatment for patients with end-stage liver disease is to receive a transplant. The findings by Dr. Tripathi and her colleagues demonstrate that a simple, affordable, and accessible intervention could potentially halt or reverse the damage to the liver, bringing new hope to those suffering from fatty liver diseases. The team’s findings underscore the value of basic scientific research, through which the scientific community continues to have a major positive impact on the lives of patients.”
Finding out whether liver proteins may also be impacted similarly by homocysteine is one of the team’s future research priorities. They anticipate that additional study will result in the creation of anti-NASH treatments.