In 2009, a team in Bradford showed that grey hair follicles are drowning in hydrogen peroxide. Catalase activity is 40–60% lower. The enzyme that makes hair colour is oxidised into inactivity. Here is what that means.
Hair colour is produced by melanocytes — specialised cells in the hair follicle bulb that synthesise melanin and transfer it to the growing hair shaft. The enzyme at the centre of this process is tyrosinase, which converts L-tyrosine to dopaquinone, the first step in the melanin synthesis pathway. When tyrosinase fails, melanin production stops and the hair grows out colourless.
The question of why tyrosinase fails with age has been debated for decades. The catalase hypothesis, developed primarily by Karin Schallreuter's group at the University of Bradford, provides the most mechanistically detailed answer currently available.
In a 2009 paper in the FASEB Journal, Wood, Schallreuter, and colleagues analysed grey and white hair shafts from human donors. They found that grey and white hair follicles accumulate hydrogen peroxide (H₂O₂) in millimolar concentrations — concentrations that are almost entirely absent in pigmented follicles. Alongside this, they found near-complete loss of catalase protein expression and near-complete loss of methionine sulfoxide reductase A and B (MsrA/B) — enzymes that repair oxidised proteins.
The causal chain is precise. H₂O₂ oxidises methionine residues in tyrosinase. Oxidised tyrosinase cannot catalyse the conversion of L-tyrosine to dopaquinone. Without dopaquinone, melanin synthesis stops. The hair grows out grey. Normally, MsrA/B would repair the oxidised methionine residues, restoring tyrosinase function. But in greying follicles, MsrA/B expression is also lost — so the repair mechanism fails simultaneously with the damage mechanism activating.
Grey hair follicles exhibit 40–60% reduced catalase activity. H₂O₂ accumulates in millimolar concentrations. Methionine sulfoxide repair is functionally lost. The result is irreversible oxidative inactivation of tyrosinase.
— Wood JM et al., FASEB Journal, 2009
The decline in catalase activity in hair follicles with age is not fully explained. Several contributing factors have been proposed: reduced expression of the catalase gene (CAT) in aged follicles, post-translational modification of catalase protein by oxidative damage (a self-reinforcing loop), and reduced availability of the haem cofactor required for catalase activity. The relative contribution of each factor is not established.
What is established is that the decline is progressive and appears to be self-reinforcing: as catalase activity falls, H₂O₂ accumulates; as H₂O₂ accumulates, it oxidises and inactivates remaining catalase; as catalase is inactivated, H₂O₂ accumulates further. This positive feedback loop may explain why greying, once started in a follicle, tends to be progressive rather than fluctuating.
Schallreuter's group identified a second mechanism operating in parallel. Tetrahydrobiopterin (BH4) is a cofactor required for the synthesis of L-tyrosine from phenylalanine — the substrate for tyrosinase. H₂O₂ oxidises BH4 to dihydrobiopterin (BH2), which is inactive. In greying follicles, BH4 levels are depleted by the same H₂O₂ accumulation that inactivates tyrosinase. The melanin synthesis pathway is therefore blocked at two points simultaneously.
One of the more striking findings from the Wood et al. paper is that the H₂O₂-induced oxidative damage affects the entire hair follicle — not just the melanocytes. The hair shaft itself, the keratinocytes, and the surrounding dermal papilla all show evidence of oxidative damage in grey follicles. This suggests that greying is not simply a melanocyte-specific failure but a broader follicular oxidative crisis. It also raises the possibility that the melanocyte stem cell depletion described in the Ito lab's 2023 Nature paper (reviewed in the companion article on white hair reversibility) may be a downstream consequence of this oxidative environment rather than an independent cause.
Vitaei verdict
The catalase hypothesis is the most mechanistically detailed explanation for hair greying currently available. The evidence is strong at the mechanistic level (human hair follicle data, not just animal models). The intervention implications are limited: oral catalase supplements have not been shown to reach the hair follicle at meaningful concentrations. The most rational approach to slowing the process is reducing systemic oxidative stress broadly — through sleep, exercise, dietary antioxidants, and UV protection — rather than targeting the follicle directly.
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