His8.5

L-Histidine Research

39 peer-reviewed studies · Evidence score: 8.5/10

Effect of L-Carnosine in children with autism spectrum disorders: a systematic review and meta-analysis of randomised controlled trials

Abraham DA et al. • Amino acids (2021)

Further studies are warranted to know the effect of L-Carnosine for ASD management.

The modified Cochrane risk of bias tool showed a low to high risk of bias.
Current data do not support the use of L-Carnosine in the management of children with ASD due to a low number of studies and sample size available.
Further studies are warranted to know the effect of L-Carnosine for ASD management.

Meta-Analysisn=215

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Solute carrier family 15 member 4, an emerging therapeutic target for systemic lupus erythematosus

Wang L et al. • International reviews of immunology (2025)

This review aims to summarize recent advances in understanding the role of SLC15A4 in disease progression of SLE and the development of SLC15A4-targeted inhibitors as well as discuss its potential as a target for SLE treatment.

Genome-wide association studies have identified SLC15A4 as a new susceptibility locus of SLE.
Further mechanistical studies have demonstrated that SLC15A4 involves in the production of type I IFNs in plasmacytoid dendritic cells (pDCs) and its necessity in B cells for autoantibody production in lupus models.
These studies strongly support the potential of SLC15A4 as a promising therapeutic target for SLE.

Systematic Review

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The Anti-Cancer Activity of the Naturally Occurring Dipeptide Carnosine: Potential for Breast Cancer

Maugeri S et al. • Cells (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.

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.

Systematic Review

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Effects of beta-alanine supplementation on Yo-Yo test performance: A meta-analysis

Grgic J • Clinical nutrition ESPEN (2021)

This meta-analysis found that beta-alanine is ergogenic for Yo-Yo test performance in athletes when the supplementation protocol lasts between 6 and 12 weeks and when using the level 2 variants of the Yo-Yo test.

When considering all available studies, there was no significant difference between the placebo/control and beta-alanine groups (SMD: 0.68; 95% confidence interval [CI]: -0.30, 1.67).
When considering only the studies that used supplementation protocols lasting between 6 and 12 weeks, there was a significant ergogenic effect of beta-alanine (SMD: 1.02; 95% CI: 0.01, 2.05).
When considering only the studies that used the level 2 variants of the Yo-Yo test, there was a significant ergogenic effect of beta-alanine (SMD: 1.41; 95% CI: 0.35, 2.48).

Meta-Analysis

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Gut Microbiota Characteristics of People with Obesity by Meta-Analysis of Existing Datasets

Gong J et al. • Nutrients (2022)

This study identified obesity microbial biomarkers, providing fertile targets for the management of obesity.

The relative abundance of Lachnoclostridium and Faecalitalea were higher in people with simple obesity, while 23 genera, including Christensenellaceae_R-7_group, Akkermansia, Alistipes, and Butyricimonas, etc., were significantly lower.
The random forest model achieved a high accuracy (AUC = 0.83).
The adenine and adenosine salvage pathway (PWY-6609) and the L-histidine degradation I pathway (HISDEG-PWY) were clustered in obese patients, while amino acid biosynthesis and degradation pathways (HISDEG-PWY, DAPLYSINESYN-PWY) were decreased.

Meta-Analysis

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Food Intolerance: The Role of Histamine

Shulpekova YO et al. • Nutrients (2021)

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.

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.

Systematic Review

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Histamine and Scombrotoxins

Hungerford JM • Toxicon : official journal of the International Society on Toxinology (2021)

These include many innovative sensors and several validated commercial test kits, many of them based on a recombinant form of the enzyme histamine dehydrogenase (HD).

Since time-and-temperature abuse is required to produce high levels of histamine in fish, management consists of ensuring proper handling by identifying hazards and critical control points (HACCP) and maintaining a "cold chain" from catch to consumption.
Much progress has been made during the last decade in the development and validation of rapid screening methods for detecting histamine in food and especially in fish products.
These include many innovative sensors and several validated commercial test kits, many of them based on a recombinant form of the enzyme histamine dehydrogenase (HD).

Systematic Review

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Histidine in Health and Disease: Metabolism, Physiological Importance, and Use as a Supplement

Holeček M • Nutrients (2020)

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.

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.

Systematic Review

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The Potential of Carnosine in Brain-Related Disorders: A Comprehensive Review of Current Evidence

Schön M et al. • Nutrients (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.

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.

Systematic Review

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Beta-alanine supplementation in high-intensity exercise

Harris RC et al. • Medicine and sport science (2012)

This systematic-review examined the effects of L-Histidine.

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.
Further research warranted to confirm findings

Systematic Review

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Carnosine and Diabetic Nephropathy

Peters V et al. • Current medicinal chemistry (2020)

In diabetic rodents, carnosine supplementation consistently improved renal histology and function and in most studies, also glucose metabolism.
Even though plasma half-life of carnosine in humans is short, first intervention studies in (pre-) diabetic patients yielded promising results.
The precise molecular mechanisms of carnosine mediated protective action, however, are still incompletely understood.

Systematic Review

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l-Histidine Supplementation in Adults and Young Children with Atopic Dermatitis (Eczema)

Gibbs NK • The Journal of nutrition (2020)

Atopic dermatitis (AD) is an incurable, inflammatory skin condition that is prevalent (∼20%) in young children.

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.

Systematic Review

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Carnosinases, their substrates and diseases

Bellia F et al. • Molecules (Basel, Switzerland) (2014)

The main substrates of these enzymes, i.e., carnosine, homocarnosine and anserine (β-alanyl-3-methyl-L-histidine) will also be described.

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.

Systematic Review

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L-carnosine modulates respiratory burst and reactive oxygen species production in neutrophil biochemistry and function: may oral dosage form of non-hydrolized dipeptide L-carnosine complement anti-infective anti-influenza flu treatment, prevention and self-care as an alternative to the conventional vaccination?

Babizhayev MA et al. • Current clinical pharmacology (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.

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.

Systematic Review

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Physiology and pathophysiology of carnosine

Boldyrev AA et al. • Physiological reviews (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.

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.

Systematic Review

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Histamine in the regulation of wakefulness

Thakkar MM • Sleep medicine reviews (2011)

These studies strongly implicate the histaminergic neurons of the TMN to play a critical role in the maintenance of high vigilance state during wakefulness.

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.

Systematic Review

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Alternative Treatments for Atopic Dermatitis: An Update

Shi K et al. • American journal of clinical dermatology (2019)

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.

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.

Systematic Reviewn=15

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Role of beta-alanine supplementation on muscle carnosine and exercise performance

Artioli GG et al. • Medicine and science in sports and exercise (2010)

In conclusion, beta-alanine supplementation seems to be a safe nutritional strategy capable of improving high-intensity anaerobic performance.

The symptoms, however, are transient and related to the increase in plasma concentration.
They can be prevented by using controlled release capsules and smaller dosing strategies.
No important side effect was related to the use of this amino acid so far.

Systematic Review

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Histamine network in atherosclerosis

Tanimoto A et al. • Trends in cardiovascular medicine (2006)

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.

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.

Systematic Review

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Probiotic Lactobacillus plantarum 299v supplementation in patients with major depression in a double-blind, randomized, placebo-controlled trial: A metabolomics study

Godzien J et al. • Journal of affective disorders (2025)

Observed metabolic changes were linked to mitochondrial dysfunction, inflammation, oxidative stress, and gut microbiota disruption.

Observed metabolic changes were linked to mitochondrial dysfunction, inflammation, oxidative stress, and gut microbiota disruption.
Despite the subtle nature of this alterations, our research successfully detected these differences and connected them to the metabolic disruptions associated with MDD.
Our findings emphasise the intricate relationship between metabolism, gut microbiota, and mental health prompting further research into the mechanisms of action of probiotics in MDD treatment.

RCT

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