Safety Profile
Known Safety Concerns
- Contraindicated in pregnancy -- may stimulate uterine contractions
- Latex cross-reactivity -- avoid in latex-allergic individuals
- Anticoagulant interaction -- enhances warfarin effect
- Occupational asthma documented with prolonged papain exposure
Contraindications
- Contraindicated in pregnancy -- may stimulate uterine contractions
- Latex cross-reactivity -- avoid in latex-allergic individuals
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
Papain is a proteolytic enzyme from unripe papaya latex, used as a digestive supplement. Has been used topically for wound debridement. Allergic reactions occur including occupational asthma in food workers. May interact with warfarin by enhancing anticoagulation. Contraindicated in pregnancy — may cause uterine contractions. Cross-reactivity with latex allergy is documented.
Biological and Chemical Classification
- Scientific Name
- Papain (cysteine protease from Carica papaya)
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%)
- Contraindicated in pregnancy -- may stimulate uterine contractions
- Latex cross-reactivity -- avoid in latex-allergic individuals
- Anticoagulant interaction -- enhances warfarin effect
- Occupational asthma documented with prolonged papain exposure
The available scientific evidence for Papain 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: 24 მარ 2026, 09:13
Evidence Distribution
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Observational / other LOW evidence YELLOWStructural and dynamic characterization of papain-like protease ligand recognition using integrated computational and biochemical approaches. ↗Allemailem KS. Structural and dynamic characterization of papain-like protease ligand recognition using integrated computational and biochemical approaches.. Int J Biol Macromol. 2026. PMID:41861871.PMID 41861871 ↗Journal Int J Biol MacromolYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41861871/
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Observational / other LOW evidence YELLOWImproved antioxidant and anti-melanogenic effects of ovalbumin derived from egg white after enzymatic hydrolysis. ↗Cho HY et al.. Improved antioxidant and anti-melanogenic effects of ovalbumin derived from egg white after enzymatic hydrolysis.. Food Sci Anim Resour. 2026. PMID:41848961.PMID 41848961 ↗Journal Food Sci Anim ResourYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41848961/
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Observational / other LOW evidence YELLOWThe effect of papain on some bacterial pathogens in poultry meat. ↗Khalefa HS et al.. The effect of papain on some bacterial pathogens in poultry meat.. Poult Sci. 2026. PMID:41846087.PMID 41846087 ↗Journal Poult SciYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41846087/
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Observational / other LOW evidence YELLOWSystematic identification of Salmonella T6SS effectors uncovers diverse new families and lipid-targeting activities. ↗Nicastro GG et al.. Systematic identification of Salmonella T6SS effectors uncovers diverse new families and lipid-targeting activities.. PLoS Biol. 2026. PMID:41843574.PMID 41843574 ↗Journal PLoS BiolYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41843574/
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Observational / other LOW evidence YELLOWDevelopment of injectable ibuprofen and resveratrol co-loaded mesoporous silica nanoparticle-based hydrogels for sustained delivery in osteoarthritis management. ↗Dethe MR et al.. Development of injectable ibuprofen and resveratrol co-loaded mesoporous silica nanoparticle-based hydrogels for sustained delivery in osteoarthritis management.. J Pharm Sci. 2026. PMID:41839392.PMID 41839392 ↗Journal J Pharm SciYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41839392/
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Observational / other LOW evidence YELLOWExposure to papain alters the integument morphology of female Rhipicephalus microplus ticks (Acari: Ixodidae). ↗Soares DS et al.. Exposure to papain alters the integument morphology of female Rhipicephalus microplus ticks (Acari: Ixodidae).. Acta Trop. 2026. PMID:41831672.PMID 41831672 ↗Journal Acta TropYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41831672/
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Observational / other LOW evidence YELLOWEnhancing tenderness and flavor of microwave-dried shrimp through ultrasonic-assisted papain pretreatment: Effects and mechanisms. ↗Luo W et al.. Enhancing tenderness and flavor of microwave-dried shrimp through ultrasonic-assisted papain pretreatment: Effects and mechanisms.. Ultrason Sonochem. 2026. PMID:41825365.PMID 41825365 ↗Journal Ultrason SonochemYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41825365/
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Observational / other LOW evidence YELLOWOptimization, Characterization and Antioxidant Activity of Fish Protein Hydrolysate from Payangka (Ophieleotris aporos) using Papain and Bromelain. ↗Fatimah F et al.. Optimization, Characterization and Antioxidant Activity of Fish Protein Hydrolysate from Payangka (Ophieleotris aporos) using Papain and Bromelain.. Pak J Biol Sci. 2026. PMID:41804243.PMID 41804243 ↗Journal Pak J Biol SciYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41804243/
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Observational / other LOW evidence YELLOWCharacterization and screening of a novel octapeptide from protein hydrolysates of Crassostrea gigas and its immunomodulatory effects on RAW264.7 cells. ↗Wang G et al.. Characterization and screening of a novel octapeptide from protein hydrolysates of Crassostrea gigas and its immunomodulatory effects on RAW264.7 cells.. Food Chem X. 2026. PMID:41799616.PMID 41799616 ↗Journal Food Chem XYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41799616/
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Observational / other LOW evidence YELLOWImpact of Plant and Microbial Proteases Treatment on Quality Characteristics of Beef Longissimus Thoracis and Lumborum. ↗Akkaya E et al.. Impact of Plant and Microbial Proteases Treatment on Quality Characteristics of Beef Longissimus Thoracis and Lumborum.. Food Sci Anim Resour. 2025. PMID:41821536.PMID 41821536 ↗Journal Food Sci Anim ResourYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41821536/
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 Papain. 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 Papain
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.