Study links low vitamin D to severe liver damage in cholestasis
Vitamin D3 metabolites measured to assess levels as liver damage biomarker

Low levels of vitamin D by-products, or metabolites, in the blood are indicative of more severe liver damage in cholestasis, according to a small study in China.
“The results suggest that the reduction of [vitamin D] metabolites levels might serve as potential indicators for the presence and severity of liver injury in cholestatic liver diseases,” wrote the study’s researchers, who noted that larger studies are needed to confirm their findings. The study, “Decoding liver injury: Vitamin D3 metabolite fingerprints in cholestatic liver disease diagnosis,” was published in Clinica Chimica Acta.
Cholestasis refers to a slowing down of the flow of bile, a fluid made in the liver and shipped to the intestines where it helps with the breakdown and absorption of fats and fat-soluble vitamins. When bile can’t flow properly, it builds up in the liver and can lead to liver damage. By preventing bile from reaching the intestines as it should, cholestasis limits the absorption of fat-soluble vitamins like vitamin D.
Vitamin D and liver damage
Scientists in China investigated whether blood vitamin D levels could be a biomarker of liver damage and its severity in cholestasis and measured levels of several metabolites of vitamin D3, a form of the vitamin that’s naturally produced in the body with sunlight exposure and found in animal-based foods.
The study included 22 healthy people (median age, 46), 26 people with cholestasis and moderate liver damage (median age, 59), and 21 cholestasis patients with severe liver damage (median age, 68). Blood vitamin D metabolite levels were significantly different between the groups and showed a downward trend from the healthy group to the cholestasis group with severe liver damage.
There was a “decrease of [vitamin D3] metabolites along with liver injury,” the researchers wrote.
Most cholestasis patients had lower than normal levels of vitamin D3 metabolites and vitamin D metabolite ratio (VMR), a biomarker of vitamin D status.
“The results suggest that the reduction of serum [vitamin D3] metabolites levels might serve as potential indicators for the presence and severity of liver injury in cholestatic liver diseases,” they wrote.
Linking metabolite levels, disease severity
The researchers then used statistical models to assess the diagnostic ability of vitamin D3 metabolites and VMR for cholestasis-related liver damage and its severity. They found that the vitamin D metabolite 24,25-(OH)2-D3 showed the highest diagnostic potential and allowed cholestasis patients to be distinguished from healthy controls with a 99.4% accuracy. Blood levels of this metabolite also let researchers discriminate between moderate and severe liver damage with an accuracy of 87%. These accuracy levels were similar to some conventional liver damage biomarkers and greater than others.
“These findings indicate that vitamin D3 metabolites, particularly 24,25-(OH)2-D3, offer greater diagnostic specificity for [cholestatic liver disease] and liver injury severity than any single conventional marker,” the researchers wrote.
Available data from six patients with moderate liver damage and six with severe liver injury showed an increase in vitamin D3 metabolite levels and a decrease in liver damage markers after treatment. This was only seen in the moderate liver damage group.
“While drug treatment can rapidly confer [liver protective] effects in patients with mild liver injury (MLI), its efficacy may be limited in patients with severe liver injury (SLI) and may not achieve comparable outcomes to those observed in MLI patients,” wrote the researchers, who took note that the small number of patients limited their ability to detect statistically meaningful effects. “This study highlights the clinical potential of vitamin D3 metabolites, particularly 24,25-(OH)2-D3 and 25-(OH)-D3, as valuable biomarkers for the diagnosis and monitoring of cholestatic liver diseases.”
“Compared with conventional [liver damage] indicators … these metabolites offer comparable or superior diagnostic performance in specific contexts, while also providing a simpler, more objective means of assessing [liver] metabolic function,” they wrote, adding larger studies should further validate “the clinical utility of these metabolites as specific indicators for liver injury and treatment effect.”