pH buffering in muscle

Hard exercise makes muscle acidic. Hydrogen ions build up as the muscle breaks down glucose without enough oxygen. Buffers take those ions up and slow the fall in pH.

Carnosine’s imidazole ring has a pKa of 6.83 (HMDB). That value sits inside the pH range of working muscle, which falls from about 7.1 towards 6.5, so the ring can take up hydrogen ions over the range where it matters (Open Heart review 2014).

How much buffering

Estimates differ. Mannion et al. 1992 put carnosine at 10 to 20 per cent of total muscle buffering. Stellingwerff 2020 estimates 6 to 7 per cent at normal levels, rising to about 15 per cent after beta-alanine loading.

Evidence across species

Animals built for sprinting hold more carnosine. Harris and colleagues measured muscle buffering in horses, greyhounds and humans and related it to carnosine content (Harris 1990). In Thoroughbred horses, type II fibres held about five times more carnosine than type I (Sewell 1992).

In human trials

The human evidence comes from beta-alanine trials, which raise muscle carnosine and then measure performance. Harris 2006 and Hill 2007 showed the rise in muscle carnosine. A 2017 meta-analysis of 40 studies found a small benefit for exercise lasting 30 seconds to 10 minutes and none for shorter or longer efforts (Saunders 2017). Whether the effect is from buffering alone or also from calcium handling is not settled. See Exercise and muscle.