Homocysteine (Hcy) is an important amino acid in your blood that helps create proteins. Hyperhomocysteinemia (HHcy) is a metabolic disorder mainly due to improper removal or accumulation of homocysteine most commonly arising from low dietary intake of Folate (Fol) or Vitamin B12 (B12), those last two vitamin can break down the levels of homocysteine and maintain the homeostasis.
The term nonalcoholic steatohepatitis (NASH) is used to describe a unique entity characterized by fatty changes with lobular hepatitis in the absence of a history of alcoholism. The main lesions described are steatosis, liver cell injury, and fibrosis.
Several recent clinical studies showed that serum Hcy levels were positively associated with NASH, and B12 and Folic levels were negatively correlated with NASH severity. However, it is not known whether HHcy has a pathogenic role in NASH.
How do vitamin B and folic acid help to slow NASH progression?
Brijesh Singh, PhD, with Duke-NUS Medical School in Singapore, and colleagues confirmed the association of homocysteine with NASH progression in preclinical models (mouse and primates) and humans.
They also observed that as hepatic homocysteine levels increase, the amino acid attaches to various liver proteins, changing their structure and impeding their functioning.
In particular, when homocysteine attaches to the syntaxin 17 (Stx17) protein, it blocks the protein from transporting and digesting fat (a process known as autophagy), which in turn induces the development and progression of fatty liver disease to NASH, they noted.
In the preclinical models, supplementing the diet with vitamin B12 and folic acid increases hepatic Stx17 levels, restores its role in autophagy, and slows NASH progression and reverses liver inflammation and fibrosis,
These findings 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.
Madhulika Tripathi, Brijesh Kumar Singh, Jin Zhou, Keziah Tikno, Anissa Widjaja, Reddemma Sandireddy, Kabilesh Arul, Siti Aishah Binte Abdul Ghani, George Goh Boon Bee, Kiraely Adam Wong, Ho Jia Pei, Shamini Guna Shekeran, Rohit Anthony Sinha, Manvendra K. Singh, Stuart Alexander Cook, Ayako Suzuki, Teegan Reina Lim, Chang-Chuen Cheah, Jue Wang, Rui-Ping Xiao, Xiuqing Zhang, Pierce Kah Hoe Chow, Paul Michael Yen, (July 8, 2022). Vitamin B12 and folate decrease inflammation and fibrosis in NASH by preventing Syntaxin 17 homocysteinylation. Journal of Hepatology. Retrieved from: https://www.journal-of-hepatology.eu/article/S0168-8278(22)02932-4/fulltext
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