Safety Profile
Known Safety Concerns
- Very limited human supplementation safety data
- Urinary hydroxyproline elevation may confound laboratory collagen turnover tests
- No established UL
- Considered safe at typical supplement amounts
Contraindications
- Very limited human supplementation safety data
- Urinary hydroxyproline elevation may confound laboratory collagen turnover tests
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
L-hydroxyproline is a post-translationally modified amino acid found almost exclusively in collagen. It is not incorporated into proteins directly during synthesis but is formed from proline after incorporation into collagen. Used as a marker of collagen turnover and in collagen supplements. Very limited safety data but considered safe.
Biological and Chemical Classification
- Scientific Name
- (2S,4R)-4-Hydroxy-L-proline
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%)
- Very limited human supplementation safety data
- Urinary hydroxyproline elevation may confound laboratory collagen turnover tests
- No established UL
- Considered safe at typical supplement amounts
The available scientific evidence for L-Hydroxyproline 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, 12:51
Evidence Distribution
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Observational / other LOW evidence YELLOWIntegrating biochemical and computational approaches to identify targeted therapeutic strategies for liver fibrosis: Effects of Telaglenastat (CB-839) on the glutaminase pathway. ↗Fakher HE et al.. Integrating biochemical and computational approaches to identify targeted therapeutic strategies for liver fibrosis: Effects of Telaglenastat (CB-839) on the glutaminase pathway.. Biochem Biophys Res Commun. 2026. PMID:41365161.PMID 41365161 ↗Journal Biochem Biophys Res CommunYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41365161/
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Observational / other LOW evidence YELLOWModulation of the Gut Microbiome and Metabolomes by Fermentation Using a Probiotic Complex in a Dysbiosis-Associated Fecal Model. ↗Kim H et al.. Modulation of the Gut Microbiome and Metabolomes by Fermentation Using a Probiotic Complex in a Dysbiosis-Associated Fecal Model.. J Microbiol Biotechnol. 2025. PMID:41309379.PMID 41309379 ↗Journal J Microbiol BiotechnolYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41309379/
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Observational / other LOW evidence YELLOWDesign and synthesis of novel spirocyclic oxindole based hybrid scaffolds: in silico docking approach towards therapeutic target exploration. ↗Upadhyay RK et al.. Design and synthesis of novel spirocyclic oxindole based hybrid scaffolds: in silico docking approach towards therapeutic target exploration.. RSC Adv. 2025. PMID:41280224.PMID 41280224 ↗Journal RSC AdvYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41280224/
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Observational / other LOW evidence YELLOWL-hydroxyproline-conjugated chitosan based hydrogel integrated with curcumin-loaded PF127 micelles to promote wound healing. ↗Nie L et al.. L-hydroxyproline-conjugated chitosan based hydrogel integrated with curcumin-loaded PF127 micelles to promote wound healing.. Int J Biol Macromol. 2025. PMID:41203164.PMID 41203164 ↗Journal Int J Biol MacromolYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41203164/
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Observational / other LOW evidence YELLOWQuantification and discovery of quality control chemical markers for Shouhui Tongbian capsules by UPLC-MS/MS. ↗Zhang J et al.. Quantification and discovery of quality control chemical markers for Shouhui Tongbian capsules by UPLC-MS/MS.. Anal Methods. 2025. PMID:40832843.PMID 40832843 ↗Journal Anal MethodsYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40832843/
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Observational / other LOW evidence YELLOWDiscovery and optimization of OA amide derivatives containing a trisubstituted l-hydroxyproline fragment as novel Omicron fusion inhibitors. ↗Hong C et al.. Discovery and optimization of OA amide derivatives containing a trisubstituted l-hydroxyproline fragment as novel Omicron fusion inhibitors.. Eur J Med Chem. 2025. PMID:40818298.PMID 40818298 ↗Journal Eur J Med ChemYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40818298/
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Observational / other LOW evidence YELLOWCompositional analysis of archaeological leather and simulated leather and their degradation research based on HRMS. ↗Yang X et al.. Compositional analysis of archaeological leather and simulated leather and their degradation research based on HRMS.. Anal Methods. 2025. PMID:40693405.PMID 40693405 ↗Journal Anal MethodsYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40693405/
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Observational / other LOW evidence YELLOW[Preparation and chromatographic performance evaluation of hydrophilic interaction chromatography stationary phase based on amino acids]. ↗Xu GG et al.. [Preparation and chromatographic performance evaluation of hydrophilic interaction chromatography stationary phase based on amino acids].. Se Pu. 2025. PMID:40610768.PMID 40610768 ↗Journal Se PuYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40610768/
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Observational / other LOW evidence YELLOWSolid-phase chromogenic method combining molecularly imprinted polymer and Simon reaction for discriminating between methamphetamine and structural analogs. ↗Saito K et al.. Solid-phase chromogenic method combining molecularly imprinted polymer and Simon reaction for discriminating between methamphetamine and structural analogs.. Anal Sci. 2025. PMID:40327283.PMID 40327283 ↗Journal Anal SciYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40327283/
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Observational / other LOW evidence YELLOWPreparation of von Hippel-Lindau (VHL) E3 ubiquitin ligase ligands exploiting constitutive hydroxyproline for benzylic amine protection. ↗Soto-Martu00ednez DM et al.. Preparation of von Hippel-Lindau (VHL) E3 ubiquitin ligase ligands exploiting constitutive hydroxyproline for benzylic amine protection.. RSC Adv. 2024. PMID:38808246.PMID 38808246 ↗Journal RSC AdvYear 2024Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/38808246/
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-Hydroxyproline. 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-Hydroxyproline
A score of 2.0 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.