Safety Profile
Known Safety Concerns
- Pyroglutamic acidosis risk with acetaminophen co-administration
- Metabolic acidosis potential at high doses
- Limited clinical evidence for nootropic claims
Contraindications
- Pyroglutamic acidosis risk with acetaminophen co-administration
- Metabolic acidosis potential at high doses
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
Pyroglutamic acid is a cyclic derivative of glutamic acid involved in the gamma-glutamyl cycle. Marketed for cognitive enhancement. High-dose pyroglutamic acidosis occurs as a clinical syndrome with acetaminophen co-administration.
Biological and Chemical Classification
- Scientific Name
- Pyroglutamic acid (5-oxoproline, pyroglutamate)
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%)
- Pyroglutamic acidosis risk with acetaminophen co-administration
- Metabolic acidosis potential at high doses
- Limited clinical evidence for nootropic claims
The available scientific evidence for Pyroglutamic Acid 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, 23:08
Evidence Distribution
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Observational / other LOW evidence YELLOWEffects of Dietary Peptides From Essence of Chicken on Neuroinflammation and Their Synergism in Neuroprotection. ↗Hu X et al.. Effects of Dietary Peptides From Essence of Chicken on Neuroinflammation and Their Synergism in Neuroprotection.. Int J Vitam Nutr Res. 2026. PMID:41873107.PMID 41873107 ↗Journal Int J Vitam Nutr ResYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41873107/
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Observational / other LOW evidence YELLOWSerum Biomarker Identification of Damp-Heat Pattern in Patients with Chronic Liver Diseases. ↗Pan YQ et al.. Serum Biomarker Identification of Damp-Heat Pattern in Patients with Chronic Liver Diseases.. Chin J Integr Med. 2026. PMID:41843023.PMID 41843023 ↗Journal Chin J Integr MedYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41843023/
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Observational / other LOW evidence YELLOWIntegrative analysis of rhizosphere metabolomics and root anatomical adaptations in wheat under drought stress: comparative insights from DH-11 and PK-13. ↗Ahmed S et al.. Integrative analysis of rhizosphere metabolomics and root anatomical adaptations in wheat under drought stress: comparative insights from DH-11 and PK-13.. Physiol Mol Biol Plants. 2026. PMID:41841140.PMID 41841140 ↗Journal Physiol Mol Biol PlantsYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41841140/
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Observational / other LOW evidence YELLOWMetabolomics reveals early pregnancy serum metabolic changes and predictive biomarkers in gestational diabetes mellitus. ↗Wang F et al.. Metabolomics reveals early pregnancy serum metabolic changes and predictive biomarkers in gestational diabetes mellitus.. Nutr Metab (Lond). 2026. PMID:41832565.PMID 41832565 ↗Journal Nutr Metab (Lond)Year 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41832565/
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Observational / other LOW evidence YELLOW[Application of chromatography-mass spectrometry in the clinical analysis of multiple sclerosis]. ↗Yao ZY et al.. [Application of chromatography-mass spectrometry in the clinical analysis of multiple sclerosis].. Se Pu. 2026. PMID:41814896.PMID 41814896 ↗Journal Se PuYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41814896/
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Observational / other LOW evidence YELLOWExploring the Impact of Eu2011Waste Exposure on Childhood Blood Pressure: Metabolomics Analysis and Risk Prediction. ↗Li MY et al.. Exploring the Impact of Eu2011Waste Exposure on Childhood Blood Pressure: Metabolomics Analysis and Risk Prediction.. Environ Health (Wash). 2026. PMID:41743803.PMID 41743803 ↗Journal Environ Health (Wash)Year 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41743803/
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Observational / other LOW evidence YELLOWGC-MS-based metabolome classification of sturgeon caviar and fish roe samples reveals unique caviar signatures, interspecies and gender variabilities. ↗Ibrahim N et al.. GC-MS-based metabolome classification of sturgeon caviar and fish roe samples reveals unique caviar signatures, interspecies and gender variabilities.. Sci Rep. 2026. PMID:41702960.PMID 41702960 ↗Journal Sci RepYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41702960/
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Observational / other LOW evidence YELLOWAn Unusual Case of 5-Oxoproline Acidosis. ↗Mu00fcller N et al.. An Unusual Case of 5-Oxoproline Acidosis.. Kidney Med. 2026. PMID:41659823.PMID 41659823 ↗Journal Kidney MedYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41659823/
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Observational / other LOW evidence YELLOWMulti-omics study identifies diagnostic metabolic signatures of early Parkinson's disease associated with dysregulated glutathione and TCA cycle metabolism. ↗Wang N et al.. Multi-omics study identifies diagnostic metabolic signatures of early Parkinson's disease associated with dysregulated glutathione and TCA cycle metabolism.. Parkinsonism Relat Disord. 2026. PMID:41643583.PMID 41643583 ↗Journal Parkinsonism Relat DisordYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41643583/
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Observational / other LOW evidence YELLOWMetabolomic insights into associations between adiposity markers and liver cancer risk: Results from a prospective cohort study and Mendelian randomization analysis. ↗Li ZY et al.. Metabolomic insights into associations between adiposity markers and liver cancer risk: Results from a prospective cohort study and Mendelian randomization analysis.. PLoS Med. 2026. PMID:41628182.PMID 41628182 ↗Journal PLoS MedYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41628182/
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 Pyroglutamic Acid. 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 Pyroglutamic Acid
A score of 2.5 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.