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Peptide

Carnosine

An antioxidant and anti-glycation dipeptide (beta-alanine + histidine); for muscle it is usually taken as beta-alanine, which is its precursor.
Category
Scientific evidence
Moderate
Number of findings
1
Sources
Our own summaries · Cited studies
Recommended dose and how to use
As carnosine, absorption is limited; for performance, beta-alanine is more efficient.

Regulatory status

Not approved

FDA (U.S.): Not approved as a drug; sold as a dietary supplement.

EMA (EU): Not approved as a drug; food supplement.

How to take it

As carnosine, absorption is limited; for performance, beta-alanine is more efficient.

Safety

Well tolerated.

Effect by goal · level of evidence

Performance

improves (modest) Low-moderate RCT (AA)
Small effect

Mainly through beta-alanine.

View the study (meta-analysis) →

Anti-glycation / anti-aging

association Low meta-analysis (AAA)
Preclinical

Meta-analysis of 20 studies (4 in humans and 16 in rodents): carnosine or beta-alanine lowered HbA1c, fasting glucose and insulin resistance (HOMA-IR). In humans the studies are few and small.

View the study (meta-analysis) →

In depth

⏱ 3 min read

Carnosine is a dipeptide formed by two amino acids (beta-alanine and histidine) present in very high concentrations in the skeletal muscle and brain of mammals, especially in type II fast-twitch muscle fibers, where it reaches millimolar concentrations; its biological functions are multiple and peculiar: it acts as an intracellular pH buffer (especially important during anaerobic exercise, when muscle accumulates hydrogen ions), as a selective endogenous antioxidant, as an antiglycation agent (it inhibits the formation of advanced glycation end products, or AGEs), and as a modulator of calcium homeostasis in myocytes.

As an oral supplement, carnosine presents a major pharmacokinetic challenge: after ingestion it is rapidly hydrolyzed by the plasma enzyme carnosinase into its constituent amino acids (beta-alanine and histidine), which significantly reduces its availability as an intact dipeptide and limits its usefulness as a supplement; most studies showing increases in muscle carnosine after oral supplementation do so by administering beta-alanine (the rate-limiting amino acid for muscle synthesis), not carnosine directly, a pharmacologically important distinction.

Oral supplementation: beta-alanine vs. carnosine

To raise muscle carnosine concentrations, oral supplementation with beta-alanine (3–6 g/day for weeks) is significantly more effective and economical than direct oral carnosine, because it bypasses the problem of plasma hydrolysis and supplies the rate-limiting amino acid for endogenous muscle carnosine synthesis; most of the clinical evidence on "carnosine" in sports performance actually comes from studies with beta-alanine, an important nuance that the commercial marketing of carnosine supplements usually omits.

Antiglycation and cellular aging

Carnosine's antiglycation mechanism is one of its most interesting aspects for aging research: glycation (the irreversible formation of advanced glycation end products, or AGEs, between sugars and proteins) is one of the central processes of cellular aging and of the chronic complications of diabetes; carnosine inhibits the formation of AGEs in vitro and in some animal models, a property that has generated sustained interest in anti-aging research and in diabetic complications.

Cataracts and eye health

A specific application with some clinical support is N-acetylcarnosine in eye drops for early senile cataracts: several small Russian studies and a meta-analysis have documented modest improvements in visual acuity and reduced cataract progression with topical application of 1 percent eye drops over months; the data are interesting, but most come from the same research group and require robust independent replication before the indication can be considered well established.

Cognitive function in older adults

In older adults, several small studies have documented modest improvements in cognitive markers and quality of life with carnosine or anserine (an analogous dipeptide) supplementation over months; the data are preliminary and the magnitude of the effect is modest.

How to take it and precautions

For muscle performance indications, beta-alanine (3–6 g/day divided into several doses over 4–12 weeks) is more effective and economical than oral carnosine; for other indications where a systemic antiglycation or antioxidant effect is sought, oral carnosine at 500–1,500 mg/day divided may provide some modest benefit despite plasma hydrolysis; for early cataracts, specific eye drops with 1 percent N-acetylcarnosine applied according to the product's directions.

Generally well tolerated at the doses used; the adverse effects described are rare and mild (digestive discomfort, occasionally headache); beta-alanine produces a characteristic effect called paresthesia (a tingling sensation, skin itching) that depends on the acute dose and disappears within 30–60 minutes, with no pathological clinical significance but bothersome for some people; to minimize paresthesia, divide the daily dose into several smaller doses and use sustained-release formulations; people with histidine hypersensitivity may have reactions; in pregnancy and breastfeeding, specific data as a supplement are limited and avoidance is recommended as a precaution; commercial products with "pure carnosine" without beta-alanine are usually less effective than the equivalent alternatives with beta-alanine for the goal of raising muscle carnosine.

References

  1. Hipkiss, A.R. (2009). Carnosine and its possible roles in nutrition and health. Adv Food Nutr Res 57. doi:10.1016/S1043-4526(09)57003-9
  2. Boldyrev, A.A.; Aldini, G.; Derave, W. (2013). Physiology and pathophysiology of carnosine. Physiol Rev 93, 4. doi:10.1152/physrev.00039.2012
  3. Babizhayev, M.A. et al. (2009). N-acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision. Drugs R D 10, 3. doi:10.2165/11536820-000000000-00000
  4. Hill, C.A. et al. (2007). Influence of beta-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity. Amino Acids 32, 2. doi:10.1007/s00726-006-0364-4
  5. Caruso, J. et al. (2012). Carnosine and exercise performance: a comprehensive review. J Strength Cond Res 26, 9. doi:10.1519/JSC.0b013e31824f2104

Information, not medical advice. Scientific evidence reflects the quality of the studies.

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