History

1900: discovery

Vladimir Gulevich (also spelled Gulewitsch) and his student Semen Amiradžibi isolated carnosine from meat extract at the University of Kharkiv. Gulevich had noticed that the known constituents of meat extract could not account for all of its nitrogen. The 1900 paper in Berichte der Deutschen Chemischen Gesellschaft described carnosine as a new organic base from meat extract (Gulewitsch and Amiradžibi 1900). Gulevich’s laboratory went on to find carnitine in 1905 and anserine in 1928 (Wikipedia: Vladimir Gulevich).

1950s onward: muscle

Sergei Severin’s group in Moscow studied carnosine in muscle. A 1956 Nature letter records the group’s synthesis of carnosine phosphate and its study as a phosphate donor in muscle extract (Nature 1956). Severin’s student Alexander Boldyrev published widely on carnosine from the 1980s, including a 1990 review with Severin on its distribution and biological significance (Boldyrev and Severin 1990) and, with Aldini and Derave, the 2013 Physiological Reviews article that is the standard reference (Boldyrev, Aldini and Derave 2013).

Work on muscle buffering in horses, greyhounds and people followed from the late 1980s (Harris 1990; Sewell 1992). In 2006 Harris and colleagues showed that beta-alanine supplementation raises human muscle carnosine (Harris 2006), which started the modern sports-supplement literature.

1990s: anti-glycation

In 1995 Alan Hipkiss proposed that carnosine protects proteins from glycation by acting as a sacrificial target for reactive sugars (Hipkiss 1995). He followed with papers on protein carbonyls and ageing (Hipkiss 1998; Hipkiss 2009).

1994: a medicine in Japan

Zinc-L-carnosine (polaprezinc) was invented by Hamari Chemicals and developed with Zeria Pharmaceutical. The first patent application was filed in 1989. Japan approved Promac granules for gastric ulcer on 1 July 1994, and the product launched on 3 October 1994. A tablet form followed in 2006 (PMDA interview form, in Japanese). China approved a generic in 2012 (Experimental and Therapeutic Medicine 2021).

1996 onward: eye drops

Mark Babizhayev proposed N-acetylcarnosine as a carnosine prodrug for the eye in 1996 and published trials in cataract from 2001 (Babizhayev 2002). Those trials have not been confirmed by independent groups. A 2017 Cochrane review found no convincing evidence that N-acetylcarnosine reverses or slows cataract and excluded the Babizhayev studies because the reviewers could not confirm that they used methods appropriate for clinical trials (Dubois and Bastawrous 2017).

2010s onward: clinical trials

Trials of oral carnosine in autism (Chez 2002), schizophrenia (Chengappa 2012), prediabetes and obesity (de Courten 2016) and type 2 diabetes (Houjeghani 2018) appeared from the 2000s. Most are small. The Humans section lists them by topic.