Key takeaways on new research about hydroquinone-induced ochronosis
- Hydroquinone-induced ochronosis is caused by tyrosinase metabolism, not HGD inhibition.
- Long-term hydroquinone use produces reactive compounds that damage dermal tissue.
- True tyrosinase inhibitors like Thiamidol offer safer alternatives for hyperpigmentation.
- Findings reshape cosmetic ingredient development and dermatology best practices.
A study from Fujita Health University, published in the British Journal of Dermatology, reveals that exogenous ochronosis caused by hydroquinone is driven by tyrosinase metabolism, not inhibition of homogentisate dioxygenase (HGD), as previously thought.
Exogenous ochronosis is a rare but serious condition marked by bluish-black pigmentation, linked to long-term hydroquinone use for hyperpigmentation. For decades, it was believed to result from HGD inhibition, an enzyme absent in human skin.
Hydroquinone risks: why tyrosinase is the real culprit
Researchers found that hydroquinone is metabolised by tyrosinase into reactive compounds that accumulate in the dermis, forming ochronotic pigments. This explains why the condition occurs only in skin with active melanocytes and highlights the need for safer, true tyrosinase inhibitors.
Hydroquinone has long been the gold standard for hyperpigmentation, but its association with ochronosis has raised safety concerns. The study confirms HGD is not expressed in skin and cannot be inhibited by hydroquinone. Instead, tyrosinase rapidly oxidises hydroquinone into harmful intermediates that diffuse into the dermis, especially in sun-damaged areas.
As Dr Shosuke Ito explains, “To investigate the underlying mechanisms of exogenous ochronosis, we examined both the potential inhibition of HGD and the metabolism of hydroquinone catalysed by tyrosinase.”
Next-gen hyperpigmentation care: tyrosinase inhibitors take the lead
The findings have major implications for ingredient development. True tyrosinase inhibitors, such as Thiamidol®, butylresorcinol, hexylresorcinol, and kojic acid, are considered safe. In contrast, compounds acting as tyrosinase substrates, like rhododendrol and raspberry ketone, carry similar risks and should be avoided, according to the research.
“Compounds that act as substrates for tyrosinase should be avoided in topical products, while highly effective and selective tyrosinase inhibitors are considered safe for use,” said Dr Ito.
By identifying tyrosinase, not HGD, as the key driver of hydroquinone-induced ochronosis, this research provides a foundation for designing next-generation skincare ingredients that reduce pigmentation without risking long-term dermal damage.