Anti-glycation and carbonyl quenching

The hypothesis

Reactive carbonyl compounds form when sugars and fats break down: methylglyoxal from glucose, 4-hydroxynonenal and acrolein from lipid oxidation. They react with proteins to form advanced glycation end products (AGEs) and advanced lipoxidation end products (ALEs), which accumulate with age and in diabetes.

In 1995 Hipkiss proposed that carnosine acts as a sacrificial target: the carbonyls react with carnosine instead of with proteins (Hipkiss 1995). He developed the idea in later reviews (Hipkiss 1998; Hipkiss 2009).

Laboratory evidence

Aldini and colleagues showed that carnosine quenches 4-hydroxynonenal (Aldini 2002). Hobart and colleagues studied carnosine’s reaction with carbonyl groups on proteins (Hobart 2004). Aldini’s 2021 review brings this work together (Free Radical Research 2021).

Animal evidence

In Zucker obese rats, carnosine reduced markers of carbonyl stress (Aldini 2011). In db/db diabetic mice, carnosine affected glucose metabolism and kidney markers (Sauerhöfer 2007; Peters 2012). Rodents lack serum carnosinase, so oral carnosine reaches their tissues in a way it does not in people.

Human evidence

Human trials in prediabetes and type 2 diabetes have measured glycation markers alongside glucose and insulin. They are small and short. See Metabolic health and the meta-analyses at Matthews 2021 and Menon 2020.