B vitamins can potentially be used to treat advanced non-alcoholic fatty liver disease

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Scientists at Duke-NUS Medical School in Singapore have discovered a mechanism that leads to an advanced form of fatty liver disease – and it turns out that vitamin B12 and folic acid supplements could reverse this process.

These findings could help people with non-alcoholic fatty liver disease, an umbrella term for a range of liver conditions affecting people who drink little or no alcohol, which affects 25% of all adults worldwide and four adults out of 10 in Singapore.

Non-alcoholic fatty liver disease involves fatty buildup in the liver and is one of the leading causes of liver transplants worldwide. Its high prevalence is due to its association with diabetes and obesity, two major public health problems in Singapore and other industrialized countries. When the disease progresses to inflammation and the formation of scar tissue, it is called non-alcoholic steatohepatitis (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 of liver cancer,” said Dr. Madhulika Tripathi, first author of the study, who is a Principal Investigator in the Hormone Regulation Laboratory of the Cardiovascular and Metabolic Program at Duke-NUS.

Currently, there is no pharmacological treatment for NASH because scientists do not understand the mechanisms of the disease. Although scientists know that NASH is associated with high blood levels of an amino acid called homocysteine, they were unsure what role, if any, it plays in the development of the disease.

Dr. Tripathi, study co-author Dr. Brijesh Singh, and their colleagues from Singapore, India, China, and the United States confirmed the association of homocysteine ​​with NASH progression in preclinical models and in humans. They also found that as homocysteine ​​levels increased in the liver, the amino acid attached to various liver proteins, changing their structure and impairing their function. In particular, when homocysteine ​​is attached to a protein called syntaxin 17, it prevents the protein from performing its role of transporting and digesting fats (known as autophagy, an essential cellular process by which cells eliminate fats). malformed proteins or damaged organelles) in fatty acid metabolism, mitochondrial turnover and prevention of inflammation. This induced the development and progression of fatty liver to NASH.

Importantly, researchers found that supplementing the diet in preclinical models with vitamin B12 and folic acid increased levels of syntaxin 17 in the liver and restored its role in autophagy. It also slowed the progression of NASH and reversed liver inflammation and fibrosis.

“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 liver homocysteine ​​levels could serve as a biomarker of NASH severity.”

Homocysteine ​​may similarly affect other liver proteins, and finding out what they are is a future research direction for the team. They hope that further research will lead to the development of anti-NASH therapies.

Professor Paul M. Yen, head of the Hormone Regulation Laboratory in the Cardiovascular and Metabolic Disorders Program at Duke-NUS and lead author of the study, said: “The potential for use of vitamin B12 and folate, which have high safety profiles and are designated as dietary supplements by the United States Food and Drug Administration, as first-line therapies for the prevention and treatment of NASH, could result in huge cost savings and reduce the health burden of NASH in developed and developing countries.

Professor Patrick Casey, Senior Associate Dean for Research at Duke-NUS, said: “Currently, the only treatment for patients with end-stage liver disease is to receive a transplant. Dr Tripathi’s findings and colleagues demonstrate that a simple, affordable and accessible intervention could potentially halt or reverse liver damage, bringing new hope to people with fatty liver disease The team’s findings highlight the value of basic scientific research, through which the scientific community continues to have a major positive impact on the lives of patients.”

The research was published in the Journal of Hepatology.

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