Safety Profile
Known Safety Concerns
- Increases histamine -- avoid in histamine intolerance
- May reduce zinc and copper absorption at high doses
- Excess has been associated with neurological symptoms in animals
- Generally safe at typical supplement doses
Contraindications
- Increases histamine -- avoid in histamine intolerance
- May reduce zinc and copper absorption at high doses
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
L-histidine is a conditionally essential amino acid and histamine precursor. It is involved in haemoglobin synthesis and immune function. At standard supplement doses it is well tolerated. Excess histidine increases histamine production — potentially problematic in individuals with histamine intolerance. High doses may reduce zinc and copper absorption.
Biological and Chemical Classification
- Scientific Name
- L-Histidine
Mechanism of Action
Information not yet available for this ingredient profile.
Clinical Evidence of Effectiveness
Information not yet available for this ingredient profile.
Pharmacokinetics
Information not yet available for this ingredient profile.
Recommended Dosage
Information not yet available for this ingredient profile.
SETI — Scientific Evidence Transparency Index
Executive Summary — Ingredient Assessment
- 10 studies reviewed
- 0 high-quality studies (meta-analysis or RCT)
- Main clinical benefit observed: Metabolic
- Evidence consistency: High consistency across studies (100%)
- Increases histamine -- avoid in histamine intolerance
- May reduce zinc and copper absorption at high doses
- Excess has been associated with neurological symptoms in animals
- Generally safe at typical supplement doses
The available scientific evidence for L-Histidine indicates notable safety signals that warrant caution. Use should be considered carefully and monitored, particularly in sensitive populations or alongside other medications.
Total SETI Score
High risk| Evidence quality | 10/40 |
| Evidence consistency | 20/20 |
| Safety signals | 0/20 |
| Study recency | 10/10 |
| Evidence transparency | 10/10 |
Evidence Summary
- 10 studies reviewed
- 0 high-quality studies (meta-analysis or systematic review)
- 0 studies identified benefits or no safety concern (GREEN)
- 10 studies reported limited or advisory safety evidence (YELLOW)
Evidence Policy
Only peer-reviewed scientific literature indexed in PubMed or comparable databases is included in this evaluation. Commercial websites, blogs, and marketing materials are excluded. All references include direct traceable links to source documents.
Last updated: 25 მარ 2026, 12:49
Evidence Distribution
-
Observational / other LOW evidence YELLOWIdentification of plasma biomarkers in a PTZ-induced Sudden Unexpected Death-like model through integrated proteomics and metabolomics methods. ↗Zheng G et al.. Identification of plasma biomarkers in a PTZ-induced Sudden Unexpected Death-like model through integrated proteomics and metabolomics methods.. Front Med (Lausanne). 2026. PMID:41877782.PMID 41877782 ↗Journal Front Med (Lausanne)Year 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41877782/
-
Observational / other LOW evidence YELLOWDiquat-induced central nervous system injury: serum multi-omics and zebrafish evidence for histidine-methylmalonate imbalance and neuroinflammation. ↗Liu Q et al.. Diquat-induced central nervous system injury: serum multi-omics and zebrafish evidence for histidine-methylmalonate imbalance and neuroinflammation.. Chem Biol Interact. 2026. PMID:41865778.PMID 41865778 ↗Journal Chem Biol InteractYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41865778/
-
Observational / other LOW evidence YELLOWUnraveling the biocatalytic mechanism of dipeptide formation using QM/MM and stopped-flow kinetic experiments. ↗Vasudevan SV et al.. Unraveling the biocatalytic mechanism of dipeptide formation using QM/MM and stopped-flow kinetic experiments.. Food Chem. 2026. PMID:41865513.PMID 41865513 ↗Journal Food ChemYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41865513/
-
Observational / other LOW evidence YELLOWActivation of L-histidine biosynthesis as a new antibiotic strategy against Mycobacterium tuberculosis. ↗Hunt DM et al.. Activation of L-histidine biosynthesis as a new antibiotic strategy against Mycobacterium tuberculosis.. Nat Commun. 2026. PMID:41864986.PMID 41864986 ↗Journal Nat CommunYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41864986/
-
Observational / other LOW evidence YELLOWPeptide-Based Block Copolymer Electrolytes as Sustainable Material Platforms for Tunable Ion Transport and Mechanical Reinforcement. ↗Lusha M et al.. Peptide-Based Block Copolymer Electrolytes as Sustainable Material Platforms for Tunable Ion Transport and Mechanical Reinforcement.. ACS Macro Lett. 2026. PMID:41860330.PMID 41860330 ↗Journal ACS Macro LettYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41860330/
-
Observational / other LOW evidence YELLOWBiomimetic smartphone sensor for point-of-care l-dopa monitoring. ↗Cui X et al.. Biomimetic smartphone sensor for point-of-care l-dopa monitoring.. Talanta. 2026. PMID:41831337.PMID 41831337 ↗Journal TalantaYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41831337/
-
Observational / other LOW evidence YELLOWBiomimetic mineralization of chemically modified glucose oxidase from Aspergillus niger in ZIF-8. ↗Staniu0161iu0107 M et al.. Biomimetic mineralization of chemically modified glucose oxidase from Aspergillus niger in ZIF-8.. Biotechnol Lett. 2026. PMID:41831077.PMID 41831077 ↗Journal Biotechnol LettYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41831077/
-
Observational / other LOW evidence YELLOWZycubo (copper histidinate), the first treatment for pediatric Menkes disease. ↗Aktaruzzaman M et al.. Zycubo (copper histidinate), the first treatment for pediatric Menkes disease.. Trends Pharmacol Sci. 2026. PMID:41820156.PMID 41820156 ↗Journal Trends Pharmacol SciYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41820156/
-
Observational / other LOW evidence YELLOWWidely targeted metabolomic and transcriptomic analyses of the effects of blue polarized light and ordinary light on Dendrobium officinale. ↗Li H et al.. Widely targeted metabolomic and transcriptomic analyses of the effects of blue polarized light and ordinary light on Dendrobium officinale.. Front Plant Sci. 2026. PMID:41815419.PMID 41815419 ↗Journal Front Plant SciYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41815419/
-
Observational / other LOW evidence YELLOW[Analysis of urine biomarkers in urothelial carcinoma based on untargeted metabolomics]. ↗Liu S et al.. [Analysis of urine biomarkers in urothelial carcinoma based on untargeted metabolomics].. Se Pu. 2026. PMID:41814906.PMID 41814906 ↗Journal Se PuYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41814906/
Score Transparency
0 of 10 approved references (score saturates at 10). More peer-reviewed studies = stronger evidence base.
Method: Q = number of approved references ÷ 10 (capped at 1.0)
Limited — mostly case reports or animal studies
Method: L = mean study-level weight across approved references. Level 1 (meta-analysis / systematic review) = 1.0; Level 2 (RCT) = 0.8; Level 3 (cohort/case-control) = 0.6; Level 4 (case report) = 0.4; Level 5 (animal / in-vitro) = 0.2.
Mixed or neutral — roughly equal benefit and risk signals
Method: D = (sum of risk-scored references − sum of benefit-scored references) ÷ total evidence score, then scaled from [−1, 1] to [0, 1]. 0.0 = pure benefit; 0.5 = neutral; 1.0 = pure risk.
One or more monitoring-level safety signals active
Method: S = 0.5 (neutral baseline) + sum of active signal severity deltas ÷ 10. Severity deltas: Critical = +2.0, High = +1.5, Moderate = +1.0, Low = +0.5. Capped at 1.0.
Final GIRI Score for L-Histidine. Risk level thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
Full methodology & data sources
The GIRI Score is computed entirely from structured data — no editorial scoring or subjective weighting is applied at any step.
- References: Only approved references are counted. Each reference is assigned an evidence level (L1–L5) and a direction (risk / neutral / benefit) by the reference manager or AI classifier.
- Safety Signals: Sourced from regulatory agencies (FDA, EMA, Health Canada, TGA, and others) and pharmacovigilance databases. Only active signals count toward the score.
- Formula version: GIRI Score v3.7.0 — Q × L × D × S × 10.
- Limitations: The score reflects published evidence and recorded signals as of the last update date. It is not a clinical risk assessment and should not replace advice from a qualified healthcare professional.
Risk Level Classification
Based on available regulatory signals and scientific evidence, this ingredient presents a low safety concern under normal conditions of use.
0–3.0
3.0–5.5
5.5–7.5
7.5–10
The score pin shows exactly where this ingredient falls on the fixed risk scale.
What drove the Low classification for L-Histidine
A score of 3.0 places this ingredient in the Low band. Thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
0 approved references.
Limited — mostly case reports or animal studies (Level 4–5).
Neutral or mixed — benefit and risk signals roughly balanced.
No active signals — S component is at neutral baseline (0.5), contributing no extra risk weight.
No major regulatory restrictions or advisories recorded across monitored jurisdictions (FDA, EMA, Health Canada, TGA, and others).
How are the Low / Moderate / High / Critical thresholds defined?
The four risk levels are fixed score bands. A score is assigned to exactly one level based on where it falls:
| Level | Score | Meaning |
|---|---|---|
| LOW | 0.0 – 2.9 | Sparse or predominantly beneficial evidence. No active safety alerts. |
| MODERATE | 3.0 – 5.4 | Mixed signals — some risk alongside benefit. Caution at high doses or in sensitive groups. |
| HIGH | 5.5 – 7.4 | Multiple studies or regulatory alerts documenting adverse effects. Professional oversight recommended. |
| CRITICAL | 7.5 – 10 | Regulatory restrictions in one or more major jurisdictions. Serious documented harm. Avoid without specialist supervision. |
Thresholds are fixed constants (GIRI_Score_Utils::LEVEL_THRESHOLDS). They do not change per ingredient and are never subject to editorial adjustment.