The AtlasAmino acidsPositively charged

HistidineHis · H

The amino acid whose side chain changes charge at almost exactly the pH of a cell, which makes it the body’s buffer, its catalyst and its grip on metals.

Status Reference · not yet an episodeSources 35Reviewed October 2026

Open in the Atlas Find it on the map

Skeletal formula — every corner and every line end is a carbon, and the hydrogens on carbon are left implied.

Molecule · His · 11 heavy atoms

Histidine

C₆H₉N₃O₂155.16 g/mol

The amino acid whose side chain changes charge at almost exactly the pH of a cell, which makes it the body’s buffer, its catalyst and its grip on metals.

Built fromthe charted ones open their own entry

C6CarbonH9Hydrogen N3Nitrogen O2Oxygen

Codes: His · H
Formula: C₆H₉N₃O₂
Molar mass: 155.16 g/mol
Systematic name: (2S)-2-amino-3-(1H-imidazol-5-yl)propanoic acid
Side chain: Imidazol-4-ylmethyl: an aromatic five-membered ring with two nitrogens; partly protonated at the pH of a cell.
Class: Positively charged
In the diet: Essential
Carbon skeleton: Glucogenic
pKa: α-COOH 1.82 · α-NH₃⁺ 9.17 · side chain 6.00
Isoelectric point: pH 7.59
Hydropathy: -3.2 (Kyte–Doolittle)
Codons: CAU CAC
Main transporters: SLC7A5 (LAT1, with CD98)

pKa and isoelectric point: Nelson and Cox, Lehninger Principles of Biochemistry, table of amino acid properties (free amino acid, 25 °C). Hydropathy: Kyte and Doolittle, J Mol Biol 1982. Essentiality: Reeds, J Nutr 2000. Formula and mass computed from the structure.

In brief

What it is

An essential amino acid with an imidazole ring for a side chain. The imidazole’s pKa is about 6, close to the pH of a cell, so histidine can carry or drop a proton with very little push ^1,2.

Why it matters

That makes it the working part of many enzymes, the main proton buffer of hemoglobin, and the grip by which proteins hold copper, zinc and heme iron ^1,2,3. It is also the precursor of histamine and of carnosine, the buffer of muscle ^1,4.

Where it runs short

Adults need it too. Men fed a histidine-free diet for five weeks slowly went into negative nitrogen balance, lost a quarter of their hematocrit and developed scaly skin, all of which reversed when histidine was restored ⁵.

Where it turns

Histidinemia, the inherited inability to break histidine down, keeps blood levels high from birth, and most people with it turn out to be well ^6,7.

Too little is a real deficiency. Too much, at least the inherited kind, mostly is not.

The molecule

Histidine’s side chain is imidazole, a flat five-membered ring with two nitrogens. One of them can take up a proton and the other can give one, and the pKa that governs this is about 6, close to the pH inside cells. No other amino acid side chain sits so near neutral, which is why histidine shows up wherever a protein needs to move a proton or to respond to small changes in acidity ^1,2.

The same nitrogens bind metals. In hemoglobin and myoglobin a histidine below the heme holds the iron; without that electron-donating ligand, model heme compounds simply oxidize in water ⁸. In proteins linked to neurodegeneration, the prion protein, amyloid-β and tau, imidazole nitrogens are the primary binding sites for copper and zinc ³.

Charge · pHHistidine carries almost no net charge at the pH of blood.

Move across the chart to read the charge at any pH.

Computed from its pKa values (α-carboxyl 1.82, α-amino 9.17, side chain 6.00) by the Henderson–Hasselbalch equation, for the free amino acid in water at 25 °C. Inside a folded protein the same groups can shift by a unit or more. The faint lines are the other amino acids.

HydropathyHistidine scores -3.2: the 7th most water-loving of the twenty.

Kyte–Doolittle hydropathy index: positive values avoid water and tend to be buried inside a folded protein, negative values sit on its surface. Each letter is an amino acid; choose one to open it.

The genetic codeHistidine has 2 codons. The code is redundant, so most single-letter changes at the third position still write histidine.

The 64 codons of the standard genetic code. Codons for histidine are marked.
1st ↓ 2nd →	U	C	A	G	3rd
U	UUUPhe	UCUSer	UAUTyr	UGUCys	U
	UUCPhe	UCCSer	UACTyr	UGCCys	C
	UUALeu	UCASer	UAAStop	UGAStop	A
	UUGLeu	UCGSer	UAGStop	UGGTrp	G
C	CUULeu	CCUPro	CAUHis	CGUArg	U
	CUCLeu	CCCPro	CACHis	CGCArg	C
	CUALeu	CCAPro	CAAGln	CGAArg	A
	CUGLeu	CCGPro	CAGGln	CGGArg	G
A	AUUIle	ACUThr	AAUAsn	AGUSer	U
	AUCIle	ACCThr	AACAsn	AGCSer	C
	AUAIle	ACAThr	AAALys	AGAArg	A
	AUGMet	ACGThr	AAGLys	AGGArg	G
G	GUUVal	GCUAla	GAUAsp	GGUGly	U
	GUCVal	GCCAla	GACAsp	GGCGly	C
	GUAVal	GCAAla	GAAGlu	GGAGly	A
	GUGVal	GCGAla	GAGGlu	GGGGly	G

Where it comes from

Humans cannot make histidine. The adult requirement is 10 mg per kilogram a day ¹. Histidine was long treated as essential only for infants; a 1975 depletion study in four healthy and three uremic men showed that adults on a histidine-free diet slowly lose nitrogen, albumin and red cells ⁵.

The decline is gradual. In that study plasma histidine fell by 82% and muscle histidine by 62% over about five weeks, while nitrogen balance drifted rather than fell off a cliff ⁵.

EssentialCannot be made in humans; the adult requirement is 10 mg per kilogram a day ¹. Its essentiality in adults was shown in 1975 by depletion in a metabolic unit ⁵.

How much

10 mg per kilogram a day for adults ¹.

Where it is in food

Any protein; meat also carries histidine in carnosine ⁴.

In the bottle · fermentedIndustrial histidine is made by fermentation in Corynebacterium glutamicum ⁹. It is the same molecule as in food.

What the body does with it

Histidine is the precursor of histamine, made by histidine decarboxylase in mast cells, the acid-controlling enterochromaffin-like cells of the stomach, and neurons of the brain ¹.

It is also half of carnosine, β-alanyl-L-histidine, a dipeptide discovered in meat in 1900 and abundant in muscle and other excitable tissues, where it buffers acid, binds metals and quenches reactive aldehydes ⁴. Carnosine synthase joins the two using ATP; the supply of β-alanine, not histidine, limits how much is made ^4,10.

Proteins rich in histidine have their own jobs. Histidine-rich glycoprotein in plasma binds heparin, heme, zinc, plasminogen and immune molecules ¹¹. Filaggrin, the skin-barrier protein, is rich in histidine; when it is broken down in the outer skin, the released histidine and its product urocanic acid become part of the skin’s natural moisturizing factor ^12,13.

Histidine's two ring nitrogens make it a good handle for a metal, and that is now a licensed drug rather than only a piece of biochemistry. In Menkes disease a faulty copper transporter means copper cannot be absorbed from the gut at all; copper histidinate delivers it by daily subcutaneous injection, and the FDA approved it for children in January 2026 ¹⁴. The amino acid is not the treatment — it is what makes the metal deliverable, which is the same trick hemoglobin has been doing with a histidine under the heme since long before anyone named it.

In three sentences each

A proton on a hair trigger

The imidazole ring gains or loses a proton near pH 6, so small shifts in acidity flip its charge; histidine side chains carry much of hemoglobin’s buffering and its release of oxygen in acid tissue, the Bohr effect ².

The catalyst in the middle

In serine proteases such as trypsin, a histidine sits between serine and aspartate in the catalytic triad and shuttles the proton that makes the serine reactive ¹.

A grip on metals

The imidazole nitrogens are the main binding sites for copper and zinc in proteins such as the prion protein, amyloid-β and tau, and a histidine holds the iron of heme in myoglobin and hemoglobin ^3,8.

How it is made, moved and broken down

Histidine’s breakdown begins with histidase, in the liver and in the skin, which makes trans-urocanic acid. In the skin, ultraviolet light converts trans- to cis-urocanate ¹, which suppresses immune responses; blocking it reduced UV-induced immune suppression and skin cancer in animals ¹⁵. In the liver the pathway runs on to formiminoglutamate and then glutamate, a last step that needs folate ¹.

Some of the histidine that is eaten never becomes anything the body chose. Gut bacteria convert it to imidazole propionate, which interferes with insulin signaling, and in 4,632 US Hispanic/Latino adults followed about 12 years the two ran in opposite directions: serum histidine was associated with LOWER incident type 2 diabetes (HR 0.75, 95% CI 0.64 to 0.86), and serum imidazole propionate and the imidazole propionate-to-histidine ratio with higher (HR 1.17 and 1.33 comparing top to bottom tertile) ¹⁶. Histidine intake raised serum imidazole propionate only in people whose gut flora were set up to make it, and higher fiber intake lowered it, partly through those same bacteria. Whether eating more histidine helps or harms may depend on who is in the gut to meet it.

Carbon skeleton · glucogenicBroken down in the liver to glutamate, which can make glucose; the last step needs folate ¹.

Into histamine and carnosineTwo small molecules with large jobs ^1,10.

Histidine
Histidine decarboxylaseHDC · vitamin B6
Histamine
Carnosine synthaseCARNS1 · ATP
Carnosine

Breakdown, which needs folateEvery enzyme on this pathway has a known inborn error ¹.

Histidine
HistidaseHAL
trans-Urocanate
Urocanase, then imidazolonepropionaseUROC1, AMDHD1
Formiminoglutamate (FIGLU)
Glutamate formiminotransferaseFTCD · folate (THF)
Glutamate

How it crosses membranes

SLC7A5 · LAT1, with CD98blood–brain barrier and placenta — in reconstituted human LAT1, histidine was the preferred substrate ¹⁷

Where it matters most

Blood: Hemoglobin’s histidines carry much of its proton buffering and the Bohr effect ².
Muscle: Holds a reserve of histidine and of carnosine ^4,5.
Skin: Filaggrin releases histidine and urocanic acid into the outer layer; histidase works here as well as in the liver ^1,12.
Mast cells, stomach and brain: Where histidine is made into histamine ¹.

When it goes wrong

Inherited

Histidinemia

HAL · autosomal recessive

High histidine and low urocanic acid in blood and skin from loss of histidase; the commonest inborn error found by screening in Japan. Early reports linked it to intellectual disability, but most people identified by newborn screening have normal intelligence ⁶.

How it is foundPlasma histidine, low skin and blood urocanic acid, HAL sequencing ⁶.

Too little

Histidine deficiency

Seen experimentally on histidine-free diets: negative nitrogen balance, falling albumin and hematocrit, rising serum iron and a scaly skin rash, reversed by repletion ⁵.

How it is foundPlasma histidine with the clinical picture ⁵.

Biomarker

Folate deficiency, by FIGLU

FTCD

Without folate the last step of histidine breakdown stalls and formiminoglutamate appears in urine. In the original reports, giving histidine for the test produced a blood response in folate-deficient patients but not in B12-deficient ones ¹⁸.

How it is foundUrine FIGLU after a histidine load; now superseded ¹⁸.

Association

Atopic dermatitis and filaggrin

FLG

Filaggrin variants predispose to eczema, and the skin’s levels of histidine and its breakdown products track both the genotype and the severity of the disease ^12,13.

How it is foundResearch measures from tape-stripped skin ¹³.

How it is measured

Plasma histidine is part of any amino acid panel, but the measurements that have mattered clinically are its products: urocanic acid, low in histidinemia ⁶; formiminoglutamate, high in folate deficiency ¹⁸; and 3-methylhistidine, a research marker of muscle breakdown and meat intake ^19,20,21.

Urine FIGLU after a histidine loadHistidine’s breakdown needs folate at its last step, so in folate deficiency the intermediate formiminoglutamate spills into urine after a histidine dose; this was the old FIGLU test ^1,18.Historical; replaced by direct folate and B12 measurement.Separated folate deficiency from B12 deficiency and controls in the original reports ¹⁸.
3-MethylhistidineHistidine methylated in the actin and myosin of muscle is released when muscle protein is broken down, so urinary 3-methylhistidine has been used as a marker of muscle breakdown ^19,22.It also comes from meat in the diet, so it tracks meat intake as well, and as a muscle marker it has not found wide clinical use ^19,20.

Food, supplements and the evidence

Establishedreplicated in people, for a named outcome

Histidine is essential in adults as well as children ^1,5.
To raise muscle carnosine, the limiting ingredient is β-alanine: 3.2 to 6.4 g a day for four weeks raised it by 42 to 64% ^23,24.

Uncertainsmall, short, mixed, surrogate or preclinical

Histidine for insulin resistance: one 12-week trial of 4 g a day in 100 Chinese women with the metabolic syndrome improved insulin resistance and waist size; it has not been replicated ²⁵.
Histidine for eczema: a 24-person adult pilot and a small children’s pilot reported falls in severity scores; the author is associated with a company developing the supplement ^12,26.
β-Alanine for exercise: benefits are mainly in efforts lasting one to four minutes, with tingling skin as the common side effect; several position-stand authors have industry ties ²⁴.
Histidine and diabetes risk, where the association is strong and the causation is not. In 205,208 UK Biobank participants including 14,066 with type 2 diabetes, histidine was inversely associated with the disease alongside glutamine and glycine, while alanine and valine ran the other way — and the Mendelian randomization, which is the part that tests causation, supported glutamine and glycine as protective and did NOT single out histidine ²⁷. A marker that tracks a disease without causing it is still useful; it is just not a reason to take it.

Sold asthe claim on the label, against the evidence

“β-alanine for sprint performance.” β-alanine raises muscle carnosine, carnosine buffers acid, and the inference is that it should help repeated sprints. A 2026 multilevel meta-analysis of 17 randomized trials found no effect on mean repeated-sprint performance (SMD −0.018, 95% CI −0.207 to 0.170), peak performance or fatigue decrement, and no moderation by dose, duration, exercise mode or training status ²⁸. The buffering is real; the event it was supposed to help is limited by phosphocreatine, not by acid.
“Carnosine for endurance and for the aging brain.” The largest performance trial gave 2 g a day to 299 people for twelve weeks and found a calf-raise difference in the under-40s at six weeks, a step-test difference in men over 40 at twelve, and nothing on grip strength or anything else ²⁹. In women specifically, a meta-analysis of 11 trials and 312 participants found a pooled effect on time to exhaustion (SMD 0.49, 95% CI 0.20 to 0.79) and imprecise estimates for everything else, with certainty rated very low across all outcomes ³⁰. For cognition, a 2026 review of 13 studies rated the strength of evidence LOW and noted that the pooled improvement came from three trials by a single research team ³¹; an earlier meta-analysis of 10 trials found one of six cognitive measures moved — delayed recall — and five did not ³². The nearest thing to a real signal is mood: 18 trials and 776 participants gave a reduction in Beck Depression Inventory score of 0.79 at moderate certainty, in studies the authors themselves describe as small, short and at moderate to high risk of bias ³³.
“Anserine, balenine and ergothioneine” — the compounds being sold now that carnosine has been tested. A 2025 narrative review of all three concludes that the diversity and limitations of the available studies do not allow their ergogenic properties to be confirmed ³⁴. That sentence is the product's own evidence base, written by people sympathetic to it.

What is strange about it

Histidinemia was screened for in newborns for years and treated with diet, until follow-up showed that most of those found had normal intelligence; a million-baby screening program found no benefit for conditions like it that turned out to be benign ^6,7,35.

Most animals carry methylated versions of carnosine, anserine or balenine, in their muscle. Humans are the exception ⁴.

In the men fed no histidine, serum iron rose as the hematocrit fell; when histidine was restored the iron fell abruptly and a burst of new red cells followed ⁵.

Where it connects

In the Atlas

TrpTryptophanAromatic AlaAlanineNonpolar, aliphatic GluGlutamateNegatively charged CuCopperElement ZnZincElement FeIronElement

Topics on the map

On the map

A star in The essential amino acids, one of 14. Essential in adults too, not only infants: adults on a histidine-free diet slowly lose nitrogen, albumin and red cells.

Find it on the map

Sources

35 sources, numbered as they are cited. Every one was checked against PubMed or its publisher before it was cited here; the note under each says what it shows and what it does not.

1
Brosnan ME, Brosnan JT. Histidine metabolism and function.J Nutr · 2020 · 150(Suppl 1):2570S–2575Sdoi:10.1093/jn/nxaa079 · PMID 33000155
Requirement, catalytic triad, histidase, urocanate, FIGLU, carnosine, histamine.
2
Berenbrink M. Evolution of vertebrate haemoglobins: histidine side chains, specific buffer value and Bohr effect.Respir Physiol Neurobiol · 2006 · 154(1–2):165–184doi:10.1016/j.resp.2006.01.002 · PMID 16481225
Histidines and hemoglobin buffering across 77 species.
3
Sóvágó I, Várnagy K, Kállay C, Grenács Á. Interactions of copper(II) and zinc(II) ions with the peptide fragments of proteins related to neurodegenerative disorders: similarities and differences.Curr Med Chem · 2023 · 30(36):4050–4071doi:10.2174/0929867329666220915140852 · PMID 36111758
Imidazole nitrogens as the primary copper and zinc binding sites.
4
Boldyrev AA, Aldini G, Derave W. Physiology and pathophysiology of carnosine.Physiol Rev · 2013 · 93(4):1803–1845doi:10.1152/physrev.00039.2012 · PMID 24137022
Carnosine’s discovery, roles and the human lack of anserine.
5
Kopple JD, Swendseid ME. Evidence that histidine is an essential amino acid in normal and chronically uremic man.J Clin Invest · 1975 · 55(5):881–891doi:10.1172/JCI108016 · PMID 1123426
Seven men in a metabolic unit; about 35 days without histidine.
6
Kawai Y, Moriyama A, Asai K, et al. Molecular characterization of histidinemia: identification of four missense mutations in the histidase gene.Hum Genet · 2005 · 116(5):340–346doi:10.1007/s00439-004-1232-5 · PMID 15806399
50 screened cases; most with normal intelligence.
7
Wilcken B, Smith A, Brown DA. Urine screening for aminoacidopathies: is it beneficial? Results of a long-term follow-up of cases detected by screening one million babies.J Pediatr · 1980 · 97(3):492–497doi:10.1016/s0022-3476(80)80216-2 · PMID 7411317
No benefit for conditions that proved benign.
8
Kitagishi H, Kano K. Synthetic heme protein models that function in aqueous solution.Chem Commun (Camb) · 2021 · 57(2):148–173doi:10.1039/d0cc07044k · PMID 33346275
The proximal histidine’s role, shown by its absence in model compounds.
9
Reiter A, Wesseling L, Wiechert W, Oldiges M. Rapid exometabolome footprinting combined with multivariate statistics: a powerful tool for bioprocess optimization.Eng Life Sci · 2024 · 25(2):2300222doi:10.1002/elsc.202300222 · PMID 39990767
Corynebacterium glutamicum as the industrial platform for L-histidine.
10
Drozak J, Veiga-da-Cunha M, Vertommen D, et al. Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1).J Biol Chem · 2010 · 285(13):9346–9356doi:10.1074/jbc.M109.095505 · PMID 20097752
The enzyme that makes carnosine.
11
Poon IKH, Patel KK, Davis DS, et al. Histidine-rich glycoprotein: the Swiss Army knife of mammalian plasma.Blood · 2011 · 117(7):2093–2101doi:10.1182/blood-2010-09-303842 · PMID 20971949
Its many ligands and roles.
12
Gibbs NK. L-histidine supplementation in adults and young children with atopic dermatitis (eczema).J Nutr · 2020 · 150(Suppl 1):2576S–2579Sdoi:10.1093/jn/nxaa200 · PMID 33000160
Pilot data; filaggrin and natural moisturizing factor. Author has commercial ties.
13
Kezic S, O’Regan GM, Yau N, et al. Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity.Allergy · 2011 · 66(7):934–940doi:10.1111/j.1398-9995.2010.02540.x · PMID 21261659
Skin histidine and urocanic acid track genotype and severity.
14
Blair HA. Copper histidinate: pediatric first approval.Paediatr Drugs · 2026 · 28(4):441–445doi:10.1007/s40272-026-00750-9 · PMID 42018271
The amino acid as a carrier rather than as a nutrient: January 2026, for Menkes disease.
15
Ullrich SE. Sunlight and skin cancer: lessons from the immune system.Mol Carcinog · 2007 · 46(8):629–633doi:10.1002/mc.20328 · PMID 17443748
cis-Urocanic acid in UV immune suppression. Largely animal work.
16
Yang H, Luo K, Peters BA, et al. Diet, gut microbiota, and histidine metabolism toward imidazole propionate production in relation to type 2 diabetes.Diabetes Care · 2025 · 48(7):1225–1232doi:10.2337/dc24-2816 · PMID 40343485
What the gut does with histidine mattered more than how much was eaten.
17
Scalise M, Galluccio M, Console L, et al. The human SLC7A5 (LAT1): the intriguing histidine/large neutral amino acid transporter and its relevance to human health.Front Chem · 2018 · 6:243doi:10.3389/fchem.2018.00243 · PMID 29988369
Histidine is LAT1’s preferred substrate in reconstituted protein.
18
Cooperman JM, Lopez R. The role of histidine in the anemia of folate deficiency.Exp Biol Med (Maywood) · 2002 · 227(11):998–1000doi:10.1177/153537020222701107 · PMID 12486209
The FIGLU test and its history.
19
Keller U. Nutritional laboratory markers in malnutrition.J Clin Med · 2019 · 8(6):775doi:10.3390/jcm8060775 · PMID 31159248
3-Methylhistidine as a muscle breakdown marker has not found wide use.
20
Said MY, Rodriguez-Niño A, Post A, et al. Meat intake and risk of mortality and graft failure in kidney transplant recipients.Am J Clin Nutr · 2021 · 114(4):1505–1517doi:10.1093/ajcn/nqab185 · PMID 34091671
Urinary 1- and 3-methylhistidine as markers of meat intake.
21
Yin X, Gibbons H, Rundle M, et al. Estimation of chicken intake by adults using metabolomics-derived markers.J Nutr · 2017 · 147(10):1850–1857doi:10.3945/jn.117.252197 · PMID 28794208
Plasma 3-methylhistidine as a marker of chicken intake.
22
Aguilera JA, Tinline-Goodfellow CT, Lees MJ, et al. Dileucine-supplemented essential amino acids support whole-body anabolism after resistance exercise and serum-stimulated cell-based anabolism.J Int Soc Sports Nutr · 2025 · 22(1):2590090doi:10.1080/15502783.2025.2590090 · PMID 41321015
Uses urinary 3-methylhistidine to creatinine to estimate muscle breakdown.
23
Harris RC, Tallon MJ, Dunnett M, et al. The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis.Amino Acids · 2006 · 30(3):279–289doi:10.1007/s00726-006-0299-9 · PMID 16554972
Four weeks of β-alanine raised muscle carnosine 42–64%.
24
Trexler ET, Smith-Ryan AE, Stout JR, et al. International Society of Sports Nutrition position stand: beta-alanine.J Int Soc Sports Nutr · 2015 · 12:30doi:10.1186/s12970-015-0090-y · PMID 26175657
Doses, effects and paraesthesia; several authors with industry ties.
25
Feng RN, Niu YC, Sun XW, et al. Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial.Diabetologia · 2013 · 56(5):985–994doi:10.1007/s00125-013-2839-7 · PMID 23361591
100 women, 4 g/day, 12 weeks; single center.
26
Tan SP, Brown SB, Griffiths CEM, et al. Feeding filaggrin: effects of L-histidine supplementation in atopic dermatitis.Clin Cosmet Investig Dermatol · 2017 · 10:403–411doi:10.2147/CCID.S146760 · PMID 29042806
24 adults; SCORAD −34% at four weeks.
27
Yang J, Wu Z, Fang J, et al. The association between amino acids and the onset and progression of type 2 diabetes mellitus: a comprehensive analysis based on UK Biobank database.J Diabetes Res · 2026 · 2026:8033429doi:10.1155/jdr/8033429 · PMID 41531546
205,208 people, 14,066 with diabetes, and a Mendelian randomization that did not confirm histidine as causal.
28
Liang W, Kong D, Wang Y, et al. No ergogenic effect of β-alanine on repeated sprint ability: a systematic review and multilevel meta-analysis of randomized controlled trials.Front Nutr · 2026 · 13:1818755doi:10.3389/fnut.2026.1818755 · PMID 41971372
Seventeen trials, three outcomes, nothing — and the null was not moved by dose, duration or training status.
29
O'Toole TE, Wingard CJ, Bariess SK, et al. Effects of carnosine supplementation on physical endurance: a placebo-controlled randomized clinical trial.J Int Soc Sports Nutr · 2026 · 23(1):2679716doi:10.1080/15502783.2026.2679716 · PMID 42308284
299 people, four performance tests, twelve weeks: two scattered subgroup findings and nothing else.
30
Gu J, Wei Y, Huang J, Bu Y, Xie S. Effects of beta-alanine supplementation on exercise performance and related physiological outcomes in women: a systematic review and meta-analysis.Front Nutr · 2026 · 13:1857513doi:10.3389/fnut.2026.1857513 · PMID 42370349
312 women, because almost everything else was men. One outcome moved, at very low certainty.
31
Hsiao YF, Fan Z, Fan YY, Chung M. The effects of carnosine on cognitive function and mental health — a systematic review and meta-analysis.Nutrients · 2026 · 18(9):1385doi:10.3390/nu18091385 · PMID 42123986
Thirteen studies to June 2025, GRADE-rated low — and the pooled positive result rests on three trials from one research team.
32
Bell SM, Hariharan R, Laud PJ, Majid A, de Courten B. Histidine-containing dipeptide supplementation improves delayed recall: a systematic review and meta-analysis.Nutr Rev · 2024 · 82(10):1372–1385doi:10.1093/nutrit/nuad135 · PMID 38013229
One test out of six moved. The other five are in the paper, which is why it is worth citing.
33
Kabthymer RH, Saadati S, Lee M, et al. Carnosine/histidine-containing dipeptide supplementation improves depression and quality of life: systematic review and meta-analysis of randomized controlled trials.Nutr Rev · 2025 · 83(2):e54–e64doi:10.1093/nutrit/nuae021 · PMID 38545720
776 participants across 18 trials, moderate certainty for depression and the authors' own warning about study size and bias.
34
Jędrejko M, Kała K, Muszyńska B. Anserine, balenine, and ergothioneine: impact of histidine-containing compounds on exercise performance — a narrative review.Nutrients · 2025 · 17(5):828doi:10.3390/nu17050828 · PMID 40077698
The compounds being sold after carnosine, reviewed before the evidence for them exists.
35
Brosco JP, Sanders LM, Dharia R, et al. The lure of treatment: expanded newborn screening and the curious case of histidinemia.Pediatrics · 2010 · 125(3):417–419doi:10.1542/peds.2009-2060 · PMID 20156889
History of screening for a benign condition.

This is education, not medical advice. Nothing on this page is written with knowledge of your history, your medications or your risks, and nothing here is a dose. Do not start or stop any treatment on the basis of it — talk to your own physician. Read the full medical disclaimer.