Bilirubin May Have Protective Role Against Vitiligo

A new study suggests that there may be a causal relationship between elevated bilirubin levels and an increased risk of vitiligo.

Danfeng Xu, of Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China, and colleagues conducted a Mendelian randomization (MR) analysis in an attempt to better define the underlying molecular mechanisms between bilirubin and vitiligo.

“Bilirubin, the end product of heme metabolism in mammals, is traditionally considered a lipophilic waste that requires elimination from the body due to its potential cytotoxicity. While high concentrations can induce cytotoxic effects, including brain damage, recent studies in both in vivo and in vitro models have demonstrated that bilirubin, at physiological levels, possesses significant antioxidant properties,” the researchers explained. “In addition to its role as an antioxidant in conditions like diabetes, obesity, and cardiovascular diseases, bilirubin levels have been found to decrease in certain skin disorders characterized by oxidative stress.”

In this study, Xu and colleagues used genome-wide association study data to better understand bilirubin’s function in relation to vitiligo. The MR analysis showed a significant causal relationship between elevated levels of total bilirubin (TBIL) and reduced risk of vitiligo (P=0.038); elevated levels of direct bilirubin (DBIL) were also linked with a reduced risk of vitiligo (P=0.013).

According to the researchers, this suggests that both TBIL and DBIL act as protective factors against vitiligo. There was no causal effect of vitiligo on direct bilirubin, suggesting a unidirectional relationship.

A bioinformatics analysis that used microarray datasets to identify differentially expressed genes (DEGs) revealed 136 DEGs in generalized vitiligo, 32 in segmental vitiligo, and nine in non-segmental vitiligo. This analysis found “enrichment in oxidative stress pathways and differential gene expression patterns across vitiligo subtypes, aligning with bilirubin’s proposed mechanism of action.”

The researchers acknowledged limitations in sample diversity and emphasized the need for further research, specifically focusing on “functional studies to translate these genetic insights into clinical applications.”

Xu D, et al. Clin Cosmet Investig Dermatol. 2025 May 6;18:1107–1119. doi:10.2147/CCID.S522604