Carnosine: 299 participants, 12 weeks at 2 grams a day and two significant results out of 126 comparisons

Carnosine is a dipeptide that buffers acid in muscle; it and beta-alanine are sold as supplements to fight “acid build-up”. The largest RCT to date (JISSN, 2026) found no difference from placebo in any of seven tests across the whole group. An effect surfaced in only two subgroups. We explain why that is weaker than it sounds, and what beta-alanine does that carnosine does not.

Carnosine: 299 participants, 12 weeks at 2 grams a day and two significant results out of 126 comparisons

Many people who search for “carnosine” actually mean zinc carnosine, a remedy for the stomach lining. It has nothing to do with endurance. This article is about a different product — L-carnosine as a sports supplement. In June the largest randomised trial to date on how it affects endurance was published, and its conclusions sound louder than the data allow.

What carnosine is and why people take it

Carnosine is a dipeptide made of beta-alanine and histidine. There is a lot of it in skeletal muscle, the heart and the brain. Its main role in sport is as an intracellular buffer: it binds hydrogen ions and stops muscle from “acidifying” quickly during intense work.

The logic of the supplement is straightforward: more carnosine in muscle means you can hold high power for longer. But the direct route has an obstacle.

Why carnosine from a capsule barely reaches muscle

Human blood contains an enzyme, serum carnosinase, that breaks carnosine down. In an experiment by de Jager and colleagues (Scientific Reports, 2023), the plasma half-life of carnosine was 1.2 minutes. According to Oppermann and colleagues (IJMS, 2021), after oral intake carnosine cannot be detected in serum, although it is excreted unchanged in the urine for up to five hours — probably because part of it hides in red blood cells.

So sports nutrition took a detour long ago: instead of carnosine, athletes are given its bottleneck, beta-alanine, from which muscle synthesises carnosine itself. The position of the International Society of Sports Nutrition (ISSN): 4–6 g of beta-alanine a day for at least 2–4 weeks markedly raises muscle carnosine and improves performance, most of all in efforts lasting 1 to 4 minutes. More in our article on beta-alanine.

What the new RCT did

Timothy O'Toole and colleagues from the University of Louisville (Journal of the International Society of Sports Nutrition, 2026) analysed secondary outcomes of the NEAT trial, which was originally designed to test whether carnosine protects the heart and blood vessels from polluted air.

  • 299 people were randomised; 283 completed baseline testing.
  • Mean age was about 45 years, 57% women; participants were recruited regardless of activity level, so these are not athletes.
  • 2 g of carnosine a day (0.5 g × 2 capsules twice a day) or a corn-starch placebo for 12 weeks.
  • Tests at 6 and 12 weeks: grip strength and holding 50% of maximum, heel raises to failure, a two-minute step-in-place test and gait speed over 4 metres.

The supplement really was absorbed: carnosine in red blood cells roughly doubled, and in urine it rose roughly sevenfold. Muscle carnosine was not measured.

What they found

Across the whole group — nothing. At neither 6 nor 12 weeks did any of the seven measures differ from placebo. Models adjusted for age and sex showed no difference either.

In subgroups — two signals:

  • in participants under 40, the number of heel raises at 6 weeks was 10.2% higher than in the placebo group (95% CI 1.6–18.9%; p = 0.018);
  • in men over 40, the number of steps in the step test at 12 weeks was 7.4% higher (95% CI 1.6–13.2%; p = 0.01).

The authors conclude that “carnosine improves muscular and cardiorespiratory endurance, with the effect limited to men”. Let us see whether the data can bear that wording.

Why it is too early to believe it

Many comparisons make chance findings inevitable. Nine groups (everyone, men, women, under and over 40, and their combinations) × seven tests × two visits add up to 126 comparisons with no correction for multiplicity. At a threshold of p < 0.05, around six of them should come out “significant” by chance alone. Two did.

The signal does not hold over time. The gain in heel raises among younger participants is there at 6 weeks, but by week 12 no significant effect is reported in that subgroup — even though blood carnosine had long since reached a plateau by then.

Per-protocol rather than intention-to-treat analysis. The carnosine group excluded not only those who skipped capsules but also “non-responders” whose urinary carnosine rose by less than 10%. No such selection is possible in the placebo group. Dropout was 38% in the carnosine group versus 26% in the placebo group — an asymmetry capable of shifting the result.

The tests are not sport-specific. The step test and heel raises are clinical assessments for the general population. No time trial, no VO₂max, no lactate.

The study does have strengths: for a supplement trial the sample is genuinely large, the funding is public (NIH) and there are no conflicts of interest. And its main — null — result is informative: 2 g of carnosine a day for 12 weeks does not change functional endurance in ordinary adults.

How to apply this

  • Need a muscle buffer for efforts of 1–4 minutes? The working tool is beta-alanine, not carnosine: the dose and effect are well documented, and the delivery mechanism is understood.
  • For the marathon and long-course triathlon a buffering supplement makes almost no difference: what limits you there is fuel and thermoregulation, not acidosis.
  • Already have carnosine in the cupboard? Do not expect harm at 2 g: in a safety study by Ali and colleagues (Nutrients, 2025), single doses of up to 10 g were well tolerated. But do not count on getting any faster either.
  • Do not confuse it with zinc carnosine — that is a stomach medication, and it has not been studied for endurance.
  • Check strength endurance with tests, not feelings — if you are trying any supplement, compare the same strength tests before and after the course.

The bottom line

  • Carnosine is rapidly broken down by a blood enzyme (plasma half-life about 1.2 minutes), so the sports standard is beta-alanine, from which muscle makes carnosine itself.
  • The 2026 RCT: 299 people, 2 g/day, 12 weeks — across the whole group, not a single difference from placebo in seven tests.
  • The two positive subgroup results (+10.2% heel raises in under-40s, +7.4% in the step test in men over 40) came out of 126 comparisons, with no multiplicity correction and with asymmetric dropout.
  • There is no reason to buy carnosine for endurance; beta-alanine makes sense only for efforts of 1–4 minutes.

Sources: O'Toole T.E., Wingard C.J., Bariess S.K., Crandell C.E., Amraotkar A.R., Gao H., Bhatnagar A. “Effects of carnosine supplementation on physical endurance: a placebo-controlled randomized clinical trial”. Journal of the International Society of Sports Nutrition, 2026;23(1):2679716. DOI: 10.1080/15502783.2026.2679716 · de Jager S., Vermeulen A., De Baere S. et al. “Acute balenine supplementation in humans as a natural carnosinase-resistant alternative to carnosine”. Scientific Reports, 2023;13:6484. DOI: 10.1038/s41598-023-33300-1 · Oppermann H., Elsel S., Birkemeyer C., Meixensberger J., Gaunitz F. “Erythrocytes Prevent Degradation of Carnosine by Human Serum Carnosinase”. International Journal of Molecular Sciences, 2021;22(23):12802. DOI: 10.3390/ijms222312802 · Trexler E.T., Smith-Ryan A.E., Stout J.R. et al. “International society of sports nutrition position stand: Beta-Alanine”. Journal of the International Society of Sports Nutrition, 2015;12:30. DOI: 10.1186/s12970-015-0090-y · Ali A.N., Su L., Newton J. et al. “Dietary Carnosine Supplementation in Healthy Human Volunteers: A Safety, Tolerability, Plasma and Brain Concentration Study”. Nutrients, 2025;17:2130. DOI: 10.3390/nu17132130