Safety Profile
Known Safety Concerns
- Raises plasma homocysteine at high doses -- cardiovascular risk
- Contraindicated in homocystinuria
- Animal data suggests methionine restriction extends lifespan
- Sulphur breath odour at high doses
Contraindications
- Raises plasma homocysteine at high doses -- cardiovascular risk
- Contraindicated in homocystinuria
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
L-methionine is an essential sulphur-containing amino acid involved in methylation, glutathione synthesis, and creatine production. High supplemental doses raise plasma homocysteine, a cardiovascular risk marker. Contraindicated in homocystinuria. Excess intake in animal models is associated with shortened lifespan.
Biological and Chemical Classification
- Scientific Name
- L-Methionine
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%)
- Raises plasma homocysteine at high doses -- cardiovascular risk
- Contraindicated in homocystinuria
- Animal data suggests methionine restriction extends lifespan
- Sulphur breath odour at high doses
The available scientific evidence for L-Methionine 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
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Observational / other LOW evidence YELLOW[Multi-strategy modification for constructing an engineered strain with efficient production of O-acetyl- l-homoserine]. ↗Niu K et al.. [Multi-strategy modification for constructing an engineered strain with efficient production of O-acetyl- l-homoserine].. Sheng Wu Gong Cheng Xue Bao. 2026. PMID:41873080.PMID 41873080 ↗Journal Sheng Wu Gong Cheng Xue BaoYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41873080/
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Observational / other LOW evidence YELLOWL-Methionine attenuates methotrexate-induced cardiotoxicity by modulating oxidative stress, inflammation, and dyslipidemia in rats. ↗Abdel-Wahab WM et al.. L-Methionine attenuates methotrexate-induced cardiotoxicity by modulating oxidative stress, inflammation, and dyslipidemia in rats.. Toxicol Rep. 2026. PMID:41853660.PMID 41853660 ↗Journal Toxicol RepYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41853660/
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Observational / other LOW evidence YELLOWThe radical SAM enzyme EpeE exhibits distinct site reactivity during the biosynthesis of the RiPP natural product epipeptide. ↗Walls WG et al.. The radical SAM enzyme EpeE exhibits distinct site reactivity during the biosynthesis of the RiPP natural product epipeptide.. Proc Natl Acad Sci U S A. 2026. PMID:41849380.PMID 41849380 ↗Journal Proc Natl Acad Sci U S AYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41849380/
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Observational / other LOW evidence YELLOWGlucose 6-phosphate: the diversity of C-methylation in sugar moieties within natural product biosynthesis. ↗Zou Z et al.. Glucose 6-phosphate: the diversity of C-methylation in sugar moieties within natural product biosynthesis.. Nat Prod Rep. 2026. PMID:41838588.PMID 41838588 ↗Journal Nat Prod RepYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41838588/
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Observational / other LOW evidence YELLOWSpecies-specific effects and trophic transfer of selenium in a freshwater food chain. ↗Lin H et al.. Species-specific effects and trophic transfer of selenium in a freshwater food chain.. Comp Biochem Physiol C Toxicol Pharmacol. 2026. PMID:41796948.PMID 41796948 ↗Journal Comp Biochem Physiol C Toxicol PharmacolYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41796948/
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Observational / other LOW evidence YELLOWEffect of solid-state fermentation on protein content, amino acid digestibility and anti-nutritional components of common beans, lentils and chickpeas. ↗Lux A et al.. Effect of solid-state fermentation on protein content, amino acid digestibility and anti-nutritional components of common beans, lentils and chickpeas.. Food Res Int. 2026. PMID:41794452.PMID 41794452 ↗Journal Food Res IntYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41794452/
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Observational / other LOW evidence YELLOWThe EP424R protein of African swine fever virus functions as a 2'-O-methyltransferase and plays an important role in viral replication. ↗Wang Z et al.. The EP424R protein of African swine fever virus functions as a 2'-O-methyltransferase and plays an important role in viral replication.. mBio. 2026. PMID:41789918.PMID 41789918 ↗Journal mBioYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41789918/
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Observational / other LOW evidence YELLOWGenome-wide identification and functional analysis of the SAMS gene family in peanut reveal the role of Ah6Q1KS5 in resistance to bacterial wilt. ↗Li Y et al.. Genome-wide identification and functional analysis of the SAMS gene family in peanut reveal the role of Ah6Q1KS5 in resistance to bacterial wilt.. BMC Plant Biol. 2026. PMID:41781867.PMID 41781867 ↗Journal BMC Plant BiolYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41781867/
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Observational / other LOW evidence YELLOWHarnessing Methyltransferase-Guided Targeting for Sequence-Specific Proximity Labeling of DNA. ↗Chen X et al.. Harnessing Methyltransferase-Guided Targeting for Sequence-Specific Proximity Labeling of DNA.. Angew Chem Int Ed Engl. 2026. PMID:41766221.PMID 41766221 ↗Journal Angew Chem Int Ed EnglYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41766221/
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Observational / other LOW evidence YELLOW5,10-Methylenetetrahydrofolate Reductaseu2500the Key Allosteric Regulator in One-Carbon Metabolism. ↗Blomgren LKM et al.. 5,10-Methylenetetrahydrofolate Reductaseu2500the Key Allosteric Regulator in One-Carbon Metabolism.. Biochemistry. 2026. PMID:41758688.PMID 41758688 ↗Journal BiochemistryYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41758688/
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-Methionine. 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-Methionine
A score of 3.5 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.