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Vitamin D supplementation reduces liver inflammation and fibrosis
Last reviewed: 03.08.2025
Chronic liver disease (CLD) is a major global health problem affecting approximately 1.5 billion people. This life-threatening disease often develops without symptoms and can eventually lead to cirrhosis or liver cancer. Currently, the only treatment for CLD is liver transplantation.
Vitamin D is widely used to improve bone health. However, this study opens up exciting prospects for repurposing this inexpensive nutrient as an adjunctive therapy for liver disease. Professor Hyo-Joon Kwon from the College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea, and colleagues studied the underlying mechanisms and therapeutic value of vitamin D in liver disease.
“In this study, we examined the effects of vitamin D on ductular response and chronic liver disease, and investigated the underlying molecular mechanisms. Our data show that vitamin D supplementation attenuates ductular response and reduces liver inflammation and fibrosis, mainly through the involvement of TXNIP,” comments Professor Kwon.
The ductular reaction is the proliferation of ductular cells (primarily cholangiocytes) in response to liver injury. Although initially protective, excessive or prolonged ductular reaction promotes inflammation and fibrosis. In a study, researchers found that low plasma vitamin D levels were associated with greater ductular reaction in patients with CKD.
Vitamin D promotes increased expression of TXNIP (thioredoxin-interacting protein). This was confirmed in a mouse experiment, in which deletion of the Txnip gene in cholangiocytes resulted in an increased ductular reaction and even worsened liver inflammation and fibrosis. In vitro analysis identified the vitamin D/TXNIP molecular axis.
“Moreover, TXNIP deficiency increases the secretion of TNF-α and TGF-β by cholangiocytes, which stimulates Kupffer cells and hepatic stellate cells, resulting in inflammation and collagen deposition,” adds Professor Kwon.
Research that facilitates early diagnosis and more effective treatment of CKD is not only warranted, it is urgently needed.
“Our preclinical data reveal a novel mechanism by which vitamin D ameliorates the course of chronic liver diseases and support the hypothesis that the vitamin D/TXNIP axis may be a promising therapeutic target in the clinical management of ductular reaction and CKD,” emphasizes Professor Kwon.
Further study is required to confirm the clinical utility of vitamin D as a standard maintenance therapy for CKD.
Ultimately, this work could improve the prognosis and quality of life of millions of people worldwide by offering safer and more personalized therapies for liver disease.
The study is published in the journal Nature Communications.