Carnosine

What it is

Carnosine is two amino acids: β-alanine and histidine. The β-alanine is the unusual part — it is not one of the twenty protein amino acids, and its position means the molecule is not built by ribosomes but assembled by a dedicated enzyme. Human skeletal muscle and brain tissue contain carnosine at millimolar concentrations, so this is a major endogenous metabolite, not a trace signal.

Its close relative anserine (a methylated form) is abundant in poultry and fish muscle, and most of the human cognitive studies have used an anserine/carnosine mixture derived from chicken extract rather than pure carnosine.

What it does in the body

Carnosine has several well-characterised chemical properties: it buffers protons, which matters during intense exercise when muscle acidifies; it chelates metals; it scavenges reactive aldehydes and reactive carbonyl species; and it inhibits glycation — the non-enzymatic sugar damage to proteins that accumulates in diabetes and ageing. Reviews describe this combination as anti-inflammatory, antioxidant, antiglycating, anticarbonylating, calcium-regulatory, immunomodulatory and chelating.

And then there is the enzyme that spoils the plan. In 2003, researchers identified the genes for human carnosinase. CN1 is a homodimeric dipeptidase with narrow specificity for Xaa-His dipeptides, including carnosine. The twist is a species difference with direct consequences for how the literature should be read: human CN1 messenger RNA and protein are brain-specific, while in mouse and rat the orthologue is detectable only in kidney. Humans also carry serum carnosinase activity that rodents largely lack.

The practical result: swallowed carnosine is substantially hydrolysed in human circulation, which is why the sports-nutrition field loads β-alanine instead. β-alanine is the rate-limiting precursor, it survives to reach muscle, and muscle then builds carnosine from it.

What the human evidence shows

Glucose metabolism. A double-blind randomised pilot trial gave 2 g of carnosine daily or placebo for 12 weeks to 30 non-diabetic people with overweight or obesity. Urinary carnosine rose, confirming the dose was taken. The expected rise in fasting insulin and insulin resistance over the study period was blunted in the carnosine group, and remained so after adjusting for age, sex and weight change (p=0.02 and p=0.04). In participants with impaired glucose tolerance, two-hour glucose and insulin were both lower than placebo. The authors called it a possible strategy for preventing type 2 diabetes — in a pilot of 30 people.

Cognition in older adults. In a double-blind randomised trial, 39 healthy volunteers aged 60 to 78 completed three months of an anserine/carnosine formula at 1 g/day or placebo. Delayed recall verbal memory on the Wechsler Memory Scale was significantly preserved versus placebo (p=0.013). Blood analysis showed reduced secretion of the inflammatory cytokines CCL-2 and IL-8, and arterial spin labelling MRI showed suppression of the age-related decline in blood flow in the posterior cingulate cortex (p=0.025). The authors reported the verbal memory finding replicated in a second randomised trial (p=0.020). A separate 13-week randomised trial in 56 people aged over 65 using chicken meat extract found significant improvement on two of six Senior Fitness Test items and on some subscores of a mental status test, with a reduction in BMI.

Exercise, via β-alanine. A systematic review and meta-analysis covering 40 studies, 65 exercise protocols and 1,461 participants found a significant but small overall effect of β-alanine supplementation (effect size 0.18, 95% CI 0.08–0.28). Exercise duration moderated the effect: benefit concentrated in tasks lasting roughly half a minute to ten minutes, and was larger for exercise capacity than for performance. Training status, continuous versus intermittent exercise and total dose did not moderate it. Co-supplementation with sodium bicarbonate produced the largest effect.

As a licensed medicine. Polaprezinc — a zinc complex of L-carnosine — was developed by two Japanese pharmaceutical companies and first approved in Japan in 1994 as a gastric mucosal protective agent for gastric ulcer. It remains in use there, and has been studied as an adjunct for Helicobacter pylori eradication. This is a genuine regulatory approval for a carnosine derivative, in one country, for one indication.

Claims and what backs them

Risks and unknowns

Low risk, well tolerated. Carnosine and β-alanine have been used in gram quantities in trials without significant safety signals. The one reliable, dose-related effect of β-alanine is paraesthesia — a harmless but genuinely unpleasant tingling or flushing of the face, scalp and hands that appears within an hour of larger doses and is the main reason split dosing and sustained-release forms exist.

Zinc is not nothing. Polaprezinc delivers zinc, and sustained high zinc intake interferes with copper absorption and can cause copper deficiency. A prescription gastric drug used under supervision in Japan is a different proposition from indefinite self-directed use.

The species problem cuts both ways. Many encouraging carnosine findings come from rodents whose circulating enzyme profile does not match ours. Treat animal carnosine results with more caution here than usual, not less.

Inconclusive areas. A 2023 narrative review reported beneficial impacts on sarcopenia prevention, cognition, neurodegenerative disorders, diabetes parameters, oral mucositis, post-chemotherapy oesophagitis and taste disturbance, gastrointestinal mucosal protection and H. pylori eradication support — while describing the evidence for senile cataracts, cardiovascular disease, schizophrenia and autistic disorders as inconclusive. That is a wide spread of quality under one heading.

Where regulators stand

The bottom line

Carnosine is a useful illustration that “endogenous and abundant” does not mean “supplementable”. Your muscles are full of it; your blood contains an enzyme that destroys the version you swallow; the field worked around this decades ago by giving the precursor instead, and that workaround has a meta-analysis behind it with a small, honest effect size.

Beyond exercise, the interesting signals — insulin resistance, verbal memory — come from small randomised trials that deserve replication rather than confidence. And the one place a carnosine compound is genuinely an approved medicine is a zinc complex, for stomach ulcers, in Japan, since 1994. That is a long way from how carnosine is marketed.

References

1. Teufel M, Saudek V, Ledig JP, et al. Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase. J Biol Chem. 2003;278(8):6521–6531 PMID 12473676
2. Boldyrev AA, Aldini G, Derave W. Physiology and pathophysiology of carnosine. Physiol Rev. 2013;93(4):1803–1845 PMID 24137022
3. de Courten B, Jakubova M, de Courten MP, et al. Effects of carnosine supplementation on glucose metabolism: pilot clinical trial. Obesity. 2016;24(5):1027–1034 PMID 27040154
4. Hisatsune T, Kaneko J, Kurashige H, et al. Effect of anserine/carnosine supplementation on verbal episodic memory in elderly people. J Alzheimers Dis. 2016;50(1):149–159 PMID 26682691
5. Szcześniak D, Budzeń S, Kopeć W, Rymaszewska J. Anserine and carnosine supplementation in the elderly: effects on cognitive functioning and physical capacity. Arch Gerontol Geriatr. 2014;59(2):485–490 PMID 24880197
6. Saunders B, Elliott-Sale K, Artioli GG, et al. β-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis. Br J Sports Med. 2017;51(8):658–669 PMID 27797728
7. Cesak O, Vostalova J, Vidlar A, Bastlova P, Student V Jr. Carnosine and beta-alanine supplementation in human medicine: narrative review and critical assessment. Nutrients. 2023;15(7):1770 PMID 37049610
8. Li M, Sun Z, Zhang H, Liu Z. Recent advances on polaprezinc for medical use (review). Exp Ther Med. 2021;22(6):1445 PMID 34721687