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His8.5
L-Histidine Research
Likely helpsHigh safety
28 peer-reviewed studies
What the evidence says
Likely helps
L-Histidine appears to help in 7 of 7 studies with measurable effects — the evidence leans clearly favourable.
Most evidence is from high-quality meta-analyses and randomised trials published 1975–2026 with a typical study size of 31 participants.
Based on 28 studies · 1 meta-analysis · 13 RCTs · 7,983 total participants
Confidence
High
What the studies found
7helped· 21 more without graded effect data
By outcome
Endurance & exercise performance
Likely helps7 studies
Therapeutic & clinical
Mostly mechanism / observational6 studies
InflammationReduced oxidative stress via carnosine · 4-8 weeks
Mostly mechanism / observational6 studies
Recovery
Mostly mechanism / observational5 studies
Glucose & metabolic
Mostly mechanism / observational4 studies
Sleep & insomnia
Mostly mechanism / observational4 studies
Skin health
Mostly mechanism / observational3 studies
Cognitive function
Mostly mechanism / observational3 studies
Anemia & hematology
Too few graded studies2 studies
Heart & blood pressure
Too few graded studies2 studies
Depression & mood
Too few graded studies1 study
Digestive health
Too few graded studies1 study
Safety profile
Too few graded studies1 study
By the numbers
Pulled from 24 studies with measurable effects
Likely real effects
50%
across studies
People studied
7,983
typical study: 31 people
Strongest designs
14
1 pooled, 13 randomised
Showed benefit
100%
7/7 studies
How long studies ran
1–3 months
2
Populations Studied
Athletes2
Breast cancer patients and mouse models1
Patients with histamine intolerance1
Patients with various conditions and liver disease1
Steady research
5 studies in the last 5 years · Latest meta-analysis: 2026
197520002026
1Anti-cancer activity in breast cancerSystematic ReviewCited 12×2023
Despite this evidence, more preclinical and clinical studies are needed to better understand carnosine's anti-tumoral activity, especially in the context of breast cancer.
Maugeri S et al. · Cells (2023)
Among the different types of cancer, breast cancer represents the most common non-skin cancer among women, accounting for an estimated 15% of all cancer-related deaths in women.
When tested in mice with induced breast cancer, carnosine proved to be non-toxic to healthy cells and exhibited chemopreventive activity by reducing tumor growth.
Some evidence has also been reported at the clinical level.
The purpose of this review is to build an extraordinarily specific method of histamine cycle assessment in regard to non-allergic intolerance and its possible dire consequences that can be suffered.
Shulpekova YO et al. · Nutrients (2021)
Most cases of clinical manifestations of histamine intolerance are non-specific due to tissue-specific distribution of different histamine receptors and the lack of reproducible and reliable diagnostic markers.
The diagnosis of histamine intolerance is fraught with difficulties, in addition to challenges related to the selection of a proper treatment strategy, the regular course of recovery, and reduced amelioration of chronic symptoms due to inappropriate treatment prescription.
The purpose of this review is to build an extraordinarily specific method of histamine cycle assessment in regard to non-allergic intolerance and its possible dire consequences that can be suffered.
Of concern should be findings of hepatic enlargement and increases in ammonia and glutamine and of decrease in branched-chain amino acids (valine, leucine, and isoleucine) in blood plasma indicating that HIS supplementation is inappropriate in patients with liver disease.
Holeček M · Nutrients (2020)
Several decades of experience have confirmed the effectiveness of HIS as a component of solutions used for organ preservation and myocardial protection in cardiac surgery.
Further studies are needed to elucidate the effects of HIS supplementation on neurological disorders, atopic dermatitis, metabolic syndrome, diabetes, uraemic anaemia, ulcers, inflammatory bowel diseases, malignancies, and muscle performance during strenuous exercise.
Signs of toxicity, mutagenic activity, and allergic reactions or peptic ulcers have not been reported, although HIS is a histamine precursor.
4Carnosine effects in brain-related disordersSystematic ReviewCited 76×2019
In this review, we aim to provide a comprehensive overview of the role of carnosine in neurological, neurodevelopmental, neurodegenerative, and psychiatric disorders, summarizing current evidence from cell, animal, and human cross-sectional, longitudinal studies, and randomized controlled trials.
Schön M et al. · Nutrients (2019)
Neurological, neurodegenerative, and psychiatric disorders represent a serious burden because of their increasing prevalence, risk of disability, and the lack of effective causal/disease-modifying treatments.
There is a growing body of evidence indicating potentially favourable effects of carnosine, which is an over-the-counter food supplement, in peripheral tissues.
In this review, we aim to provide a comprehensive overview of the role of carnosine in neurological, neurodevelopmental, neurodegenerative, and psychiatric disorders, summarizing current evidence from cell, animal, and human cross-sectional, longitudinal studies, and randomized controlled trials.
This systematic-review examined the effects of L-Histidine.
Harris RC et al. · Medicine and sport science (2012)
Increasing muscle carnosine through increased dietary intake of β-alanine will increase the intracellular buffering capacity, which in turn might be expected to increase high-intensity exercise capacity and performance where this is pH limited.
Atopic dermatitis (AD) is an incurable, inflammatory skin condition that is prevalent (∼20%) in young children.
Gibbs NK · The Journal of nutrition (2020)
Huge benefit
← WorseNo effectBetter →
Likely real
Atopic dermatitis (AD) is an incurable, inflammatory skin condition that is prevalent (∼20%) in young children.
Unlike the placebo, l-histidine reduced AD (34% reduction in SCORing Atopic Dermatitis scores; P < 0.003) after 4 wk.
A survey of adults (n = 98) taking 4 g l-histidine daily reiterated a lack of causal AEs and also reported a 33% reduction in topical corticosteroid use.
8Carnosinase function and substratesSystematic ReviewCited 84×2014
The main substrates of these enzymes, i.e., carnosine, homocarnosine and anserine (β-alanyl-3-methyl-L-histidine) will also be described.
Bellia F et al. · Molecules (Basel, Switzerland) (2014)
For this reason the use of carnosinase levels as a biomarker in cerebrospinal fluid (CSF) has been questioned.
The hydrolysis of imidazole-related dipeptides in prokaryotes and eukaryotes is also catalyzed by aminoacyl-histidine dipeptidases like PepD (EC 3.4.13.3), PepV (EC 3.4.13.19) and anserinase (EC 3.4.13.5).
The review deals with the structure and function of this class of enzymes in physiological and pathological conditions.
9Neutrophil function and influenza treatmentSystematic ReviewCited 9×2014
The data presented in this article, overall, may have implications for global influenza surveillance and planning for pandemic influenza therapeutic prevention with oral forms of non-hydrolized natural L-carnosine as a suitable alternative to the conventional vaccination for various flu ailments.
Babizhayev MA et al. · Current clinical pharmacology (2014)
Carnosine and anserine were also found to reduce apoptosis of human neutrophils.
In this way these histidine-containing compounds can modulate the Influenza virus release from neutrophills and reduce virus dissemination through the body of the organism.
The data presented in this article, overall, may have implications for global influenza surveillance and planning for pandemic influenza therapeutic prevention with oral forms of non-hydrolized natural L-carnosine as a suitable alternative to the conventional vaccination for various flu ailments.
10Carnosine physiology and pathophysiologySystematic ReviewCited 828×2013
However, far more experiments in the fields of physiology and related disciplines (biology, pharmacology, genetics, molecular biology, etc.) are required to gain a full understanding of the function and applications of this intriguing molecule.
Boldyrev AA et al. · Physiological reviews (2013)
Also the pathophysiological relevance of serum carnosinase, the enzyme actively degrading carnosine into l-histidine and β-alanine, is discussed.
The carnosine system has evolved as a pluripotent solution to a number of homeostatic challenges. l-Histidine, and more specifically its imidazole moiety, appears to be the prime bioactive component, whereas β-alanine is mainly regulating the synthesis of the dipeptide.
This paper summarizes a century of scientific exploration on the (patho)physiological role of carnosine and related compounds.
These studies strongly implicate the histaminergic neurons of the TMN to play a critical role in the maintenance of high vigilance state during wakefulness.
Thakkar MM · Sleep medicine reviews (2011)
The cerebrospinal levels of histamine are reduced in diseased states where hypersomnolence is a major symptom.
The histamine deficient L-histidine decarboxylase knockout (HDC KO) mice display sleep fragmentation and increased REM sleep during the light period along with profound wakefulness deficit at dark onset, and in novel environment.
Similar results have been obtained when histamine neurons are lesioned.
12Atopic dermatitis treatment alternativesSystematic ReviewCited 19×n=15 · very small study2019
Future investigative efforts should focus on reproducing some of these studies with a larger sample size whose clinical characteristics and demographics are more reflective of the general AD population, and standardizing the process to produce reliable data.
Shi K et al. · American journal of clinical dermatology (2019)
This update aims to aggregate and review these new data.
The preliminary results for many treatments such as vitamin E, East Indian Sandalwood Oil (EISO), melatonin, L-histidine, and Manuka honey show positive clinical effects, but there is currently not enough evidence to recommend their use in AD therapy.
Future investigative efforts should focus on reproducing some of these studies with a larger sample size whose clinical characteristics and demographics are more reflective of the general AD population, and standardizing the process to produce reliable data.
More high-quality RCTs are needed to verify these findings and to improve the certainty level of this body of evidence.
Hsiao YF et al. · Nutrients (2026)
Overall 58% of included RCTs were rated 'some concerns' for ROB.
Additionally, meta-analysis results showed that L-carnosine combined with anserine or antioxidant supplementation significantly improved the MMSE score compared to placebo (pooled net change = 0.62; 95% CI 0.23, 1.01), with small statistical heterogeneity (I2 = 21.3%).
Most of the studies did not show significant effects in a wide range of mood and depression outcome measures or health-related QOL (data cannot be meta-analyzed).
Because H1 and H2 receptors are discovered previously, the activities through those receptors are investigated relatively well, but as the other two types of receptors have been cloned recently, their involvement in atherosclerotic lesion should be investigated further.
Tanimoto A et al. · Trends in cardiovascular medicine (2006)
We recently observed the histidine decarboxylase-gene knockout mice ameliorates' atherosclerotic region, compared with that of the wild-type control mice.
The source of histamine in atherosclerotic lesion should be clarified in details; however, it could be macrophage, endothelial cells, and mast cells.
All four types of histamine receptors (H1-H4) have the possibilities to be involved in the atherosclerotic regions.
15High-intensity exercise capacityRCTCited 23×n=235 · medium study2014
Acute carnosine supplementation does not improve high-intensity performance.
Baguet A et al. · Journal of applied physiology (Bethesda, Md. : 1985) (2014)
In a subsequent double-blind, placebo-controlled, crossover study, 12 men performed a cycling capacity test at 110% maximal power output (CCT 110%) following acute carnosine (20 mg/kg body wt) or placebo supplementation.
Both male and female explosive athletes had significantly lower CN1 activity (14% and 21% lower, respectively) and content (30% and 33% lower, respectively) than controls.
The CCT 110% performance was not improved after carnosine supplementation, even when accounting for low/high CN1 content.
17Exercise-induced oxidative stressRCTCited 16×n=10 · very small study2020
However, anserine temporal elevated exercise-induced cell-damage, together with enhanced antioxidant activity and haematological responses suggest an augmented exercise-induced adaptative response and recovery.
Alkhatib A et al. · Nutrients (2020)
Huge benefit
← WorseNo effectBetter →
Likely real
Anserine supplementation increased superoxide dismutase (SOD) by 50% (p < 0.001, effect size d = 0.8 for both ANS-LD and ANS-HD), and preserved catalase (CAT) activity suggesting an improved antioxidant activity.
Haematological biomarkers were largely unaffected by anserine, its dose, and without interaction with post exercise time-course.
However, compared with ANS-LD and PLA, ANS-HD increased the mean cell volume (MCV), and decreased the mean corpuscular haemoglobin concentration (MCHC) (p < 0.001).
18Gulf War illness symptomsRCTCited 76×n=25 · very small study2013
Fatigue, pain, hyperalgesia, activity and other outcomes were resistant to treatment.
Baraniuk JN et al. · Global journal of health science (2013)
About 25% of 1990-1991 Persian Gulf War veterans experience disabling fatigue, widespread pain, and cognitive dysfunction termed Gulf War illness (GWI) or Chronic Multisymptom Illness (CMI).
To determine if nutritional supplementation with L-carnosine would significantly improve pain, cognition and fatigue in GWI, a randomized double blind placebo controlled 12 week dose escalation study involving 25 GWI subjects was employed.
Carnosine had 2 potentially beneficial effects: WAIS-R scores increased significantly, and there was a decrease in diarrhea associated with irritable bowel syndrome.
19Intramuscular carnosine content and fatigue attenuationRCTCited 30×2017
Changes in muscle BA following supplementation was unclear in men, likely elevated in women, but unclear between sexes (mean sex difference: 0.03 ± 0.42 mmol·kg-1 ww).
Varanoske AN et al. · Nutrition research (New York, N.Y.) (2017)
Noticeable benefit
← WorseNo effectBetter →
Changes in muscle BA following supplementation was unclear in men, likely elevated in women, but unclear between sexes (mean sex difference: 0.03 ± 0.42 mmol·kg-1 ww).
In conclusion, BA supplementation increased muscle carnosine and attenuated fatigue in men and women similarly but did not reduce muscle l-histidine.
This study suggests that L-carnosine, added to conventional therapy, has beneficial effects on exercise performance and quality of life in stable CHF.
Lombardi C et al. · Nutrition (Burbank, Los Angeles County, Calif.) (2015)
Patients receiving orodispersible L-carnosine had an improvement in 6 MWT distance (P = 0.014) and in quality-of-life (VAS score) (P = 0.039) between baseline and follow-up.
This study suggests that L-carnosine, added to conventional therapy, has beneficial effects on exercise performance and quality of life in stable CHF.
More data are necessary to evaluate its effects on left-ventricular ejection fraction and prognosis in CHF.