Safety Profile
Known Safety Concerns
- FDA 2022 determination: excluded from supplement definition -- legal grey area
- Anticoagulant effect at high doses -- caution with blood thinners
- May lower blood pressure and blood sugar
- Nausea and GI distress at high doses
Contraindications
- FDA 2022 determination: excluded from supplement definition -- legal grey area
- Anticoagulant effect at high doses -- caution with blood thinners
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
NAC is a precursor to glutathione and a mucolytic agent used as a supplement for liver support, respiratory health, and PCOS. In 2022, the FDA issued warning letters stating that NAC is excluded from the definition of a dietary supplement because it was studied as a drug (IV acetylcysteine for paracetamol overdose) before being marketed as a supplement. It is anticoagulant at high doses and may lower blood pressure.
Biological and Chemical Classification
- Scientific Name
- N-Acetyl-L-cysteine
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%)
- FDA 2022 determination: excluded from supplement definition -- legal grey area
- Anticoagulant effect at high doses -- caution with blood thinners
- May lower blood pressure and blood sugar
- Nausea and GI distress at high doses
The available scientific evidence for NAC (N-Acetyl Cysteine) 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: 23 მარ 2026, 18:49
Evidence Distribution
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Observational / other LOW evidence YELLOWGSDME-mediated pyroptosis is essential for the chemotherapeutic effects achieved by combined treatment of temsirolimus and 5-fluorouracil in ovarian carcinoma cells. ↗Chen Z et al.. GSDME-mediated pyroptosis is essential for the chemotherapeutic effects achieved by combined treatment of temsirolimus and 5-fluorouracil in ovarian carcinoma cells.. Am J Transl Res. 2026. PMID:41868939.PMID 41868939 ↗Journal Am J Transl ResYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41868939/
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Observational / other LOW evidence YELLOWROS-NLRP3 participates in the pyroptosis response of excretory-secretory products from protoscoleces of Echinococcus granulosus in hepatocytes. ↗Cao J et al.. ROS-NLRP3 participates in the pyroptosis response of excretory-secretory products from protoscoleces of Echinococcus granulosus in hepatocytes.. Sci Rep. 2026. PMID:41862686.PMID 41862686 ↗Journal Sci RepYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41862686/
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Observational / other LOW evidence YELLOWNanomolar Cadmium Disrupts Neurotransmitter Release Timing via a ROS-dependent Mechanism at the Mouse Neuromuscular Junction: Modulation by Nanomolar Zn(2). ↗Khaziev AN et al.. Nanomolar Cadmium Disrupts Neurotransmitter Release Timing via a ROS-dependent Mechanism at the Mouse Neuromuscular Junction: Modulation by Nanomolar Zn(2).. Neurochem Res. 2026. PMID:41854772.PMID 41854772 ↗Journal Neurochem ResYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41854772/
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Observational / other LOW evidence YELLOWSafe dosage and potential risks of chlorogenic acid: insights from in vitro and in vivo studies. ↗Pang Y et al.. Safe dosage and potential risks of chlorogenic acid: insights from in vitro and in vivo studies.. Front Pharmacol. 2026. PMID:41815919.PMID 41815919 ↗Journal Front PharmacolYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41815919/
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Observational / other LOW evidence YELLOWSynthesis and characterizations of N-Acetyl-L-Cysteine capped ZnSe core and ZnSe/CdSe core-shell quantum dots: selective sensing of picric acid and phosphor-converted LED applications. ↗Kalita M et al.. Synthesis and characterizations of N-Acetyl-L-Cysteine capped ZnSe core and ZnSe/CdSe core-shell quantum dots: selective sensing of picric acid and phosphor-converted LED applications.. Spectrochim Acta A Mol Biomol Spectrosc. 2026. PMID:41806768.PMID 41806768 ↗Journal Spectrochim Acta A Mol Biomol SpectroscYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41806768/
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Observational / other LOW evidence YELLOWMicrocystin-LR impacts viability, migration, and proliferation of the Atlantic salmon gill epithelial cell line, ASG-10: implications for tissue repair. ↗Ghanizadeh-Kazerouni E et al.. Microcystin-LR impacts viability, migration, and proliferation of the Atlantic salmon gill epithelial cell line, ASG-10: implications for tissue repair.. Comp Biochem Physiol C Toxicol Pharmacol. 2026. PMID:41786110.PMID 41786110 ↗Journal Comp Biochem Physiol C Toxicol PharmacolYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41786110/
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Observational / other LOW evidence YELLOWPolystyrene Nanoplastics and Cadmium Co-Exposure Accelerates Mitochondrial Autophagy Mediated by HSP60-SIRT3-SOD(2) Signaling Pathway in Primary Duck Embryo Hepatocytes. ↗Chen Y et al.. Polystyrene Nanoplastics and Cadmium Co-Exposure Accelerates Mitochondrial Autophagy Mediated by HSP60-SIRT3-SOD(2) Signaling Pathway in Primary Duck Embryo Hepatocytes.. J Agric Food Chem. 2026. PMID:41783983.PMID 41783983 ↗Journal J Agric Food ChemYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41783983/
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Observational / other LOW evidence YELLOWThe ethyl acetate extract of Schefflera kwangsiensis ameliorates oxaliplatin-induced peripheral neuropathic pain via SERCA2b. ↗Li J et al.. The ethyl acetate extract of Schefflera kwangsiensis ameliorates oxaliplatin-induced peripheral neuropathic pain via SERCA2b.. Chin J Nat Med. 2026. PMID:41781120.PMID 41781120 ↗Journal Chin J Nat MedYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41781120/
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Observational / other LOW evidence YELLOWEffects of thiol compounds on DNA-damage detection and in vitro fertilization outcomes in bovine sperm. ↗Takeda K et al.. Effects of thiol compounds on DNA-damage detection and in vitro fertilization outcomes in bovine sperm.. J Reprod Dev. 2026. PMID:41780946.PMID 41780946 ↗Journal J Reprod DevYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41780946/
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Observational / other LOW evidence YELLOWGallic Acid as a Non-cytotoxic Modulator of the ROS-EGFR-ERK-EMT Axis in Xenograft-derived T98G Glioblastoma Cells. ↗Su YF et al.. Gallic Acid as a Non-cytotoxic Modulator of the ROS-EGFR-ERK-EMT Axis in Xenograft-derived T98G Glioblastoma Cells.. Anticancer Res. 2026. PMID:41760275.PMID 41760275 ↗Journal Anticancer ResYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41760275/
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 NAC (N-Acetyl Cysteine). 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 moderate safety concern. Caution is advised, particularly at high doses or in sensitive populations.
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 Moderate classification for NAC (N-Acetyl Cysteine)
A score of 4.0 places this ingredient in the Moderate 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.