Safety Profile
Known Safety Concerns
- 2021 study: NR promoted breast cancer metastasis in animal models (human relevance unresolved)
- FDA has raised concerns about supplement classification -- may be a drug
- No long-term (beyond 12 weeks) human safety data
- Avoid in individuals with breast cancer or at high breast cancer risk until further data available
Contraindications
- 2021 study: NR promoted breast cancer metastasis in animal models (human relevance unresolved)
- FDA has raised concerns about supplement classification -- may be a drug
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
Nicotinamide riboside is an NAD+ precursor available as Niagen and similar products. Short-term human trials (up to 8 weeks) show it raises blood NAD+ levels safely. FDA has questioned whether NR can be marketed as a supplement (similar to NMN concerns). A 2021 study found NR supplementation promoted metastasis of estrogen receptor-positive breast cancer cells in mouse models — a significant and unresolved safety signal requiring further research.
Biological and Chemical Classification
- Scientific Name
- Nicotinamide riboside chloride
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%)
- 2021 study: NR promoted breast cancer metastasis in animal models (human relevance unresolved)
- FDA has raised concerns about supplement classification -- may be a drug
- No long-term (beyond 12 weeks) human safety data
- Avoid in individuals with breast cancer or at high breast cancer risk until further data available
The available scientific evidence for NR (Nicotinamide Riboside) 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, 10:59
Evidence Distribution
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Observational / other LOW evidence YELLOWNicotinamide mononucleotide and nicotinamide riboside attenuate cytokine production in human keratinocytes via suppression of p38 Pathway. ↗Xie C et al.. Nicotinamide mononucleotide and nicotinamide riboside attenuate cytokine production in human keratinocytes via suppression of p38 Pathway.. Mol Biol Rep. 2026. PMID:41779073.PMID 41779073 ↗Journal Mol Biol RepYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41779073/
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Observational / other LOW evidence YELLOWAcetylation of PRDX5 aggravates the oxidative stress and apoptosis of retinal neurons induced by ischemia-reperfusion. ↗Lu S et al.. Acetylation of PRDX5 aggravates the oxidative stress and apoptosis of retinal neurons induced by ischemia-reperfusion.. Tissue Cell. 2026. PMID:41740330.PMID 41740330 ↗Journal Tissue CellYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41740330/
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Observational / other LOW evidence YELLOWHair growth enhancement via mitochondrial activation by Mito-activator complex. ↗Lee IG et al.. Hair growth enhancement via mitochondrial activation by Mito-activator complex.. Int J Cosmet Sci. 2026. PMID:41657103.PMID 41657103 ↗Journal Int J Cosmet SciYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41657103/
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Observational / other LOW evidence YELLOWTargeting SIRT3 to regulate mitophagy-dependent ferroptosis for preventing glucocorticoid-induced osteoporosis. ↗Hu Y et al.. Targeting SIRT3 to regulate mitophagy-dependent ferroptosis for preventing glucocorticoid-induced osteoporosis.. Int J Surg. 2025. PMID:40607908.PMID 40607908 ↗Journal Int J SurgYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40607908/
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Observational / other LOW evidence YELLOWNMRK2 is an efficient diagnostic indicator for Xp11.2 translocation renal cell carcinoma. ↗Feng H et al.. NMRK2 is an efficient diagnostic indicator for Xp11.2 translocation renal cell carcinoma.. J Pathol. 2024. PMID:39092712.PMID 39092712 ↗Journal J PatholYear 2024Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/39092712/
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Observational / other LOW evidence YELLOWMaternal Administration of Acetaminophen Affects Meiosis Through its Metabolite NAPQI Targeting SIRT7 in Fetal Oocytes. ↗Liu F et al.. Maternal Administration of Acetaminophen Affects Meiosis Through its Metabolite NAPQI Targeting SIRT7 in Fetal Oocytes.. Antioxid Redox Signal. 2024. PMID:38062739.PMID 38062739 ↗Journal Antioxid Redox SignalYear 2024Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/38062739/
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Observational / other LOW evidence YELLOWRaising NAD(+) Level Stimulates Short-Chain Dehydrogenase/Reductase Proteins to Alleviate Heart Failure Independent of Mitochondrial Protein Deacetylation. ↗Walker MA et al.. Raising NAD(+) Level Stimulates Short-Chain Dehydrogenase/Reductase Proteins to Alleviate Heart Failure Independent of Mitochondrial Protein Deacetylation.. Circulation. 2023. PMID:37965787.PMID 37965787 ↗Journal CirculationYear 2023Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/37965787/
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Observational / other LOW evidence YELLOWAlterations in Intestinal Brush Border Membrane Functionality and Bacterial Populations Following Intra-Amniotic Administration (Gallus gallus) of Nicotinamide Riboside and Its Derivatives. ↗Kolba N et al.. Alterations in Intestinal Brush Border Membrane Functionality and Bacterial Populations Following Intra-Amniotic Administration (Gallus gallus) of Nicotinamide Riboside and Its Derivatives.. Nutrients. 2022. PMID:35956307.PMID 35956307 ↗Journal NutrientsYear 2022Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/35956307/
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Observational / other LOW evidence YELLOWAcute Treatment with Nicotinamide Riboside Chloride Reduces Hippocampal Damage and Preserves the Cognitive Function of Mice with Ischemic Injury. ↗Cheng YH et al.. Acute Treatment with Nicotinamide Riboside Chloride Reduces Hippocampal Damage and Preserves the Cognitive Function of Mice with Ischemic Injury.. Neurochem Res. 2022. PMID:35585298.PMID 35585298 ↗Journal Neurochem ResYear 2022Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/35585298/
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Observational / other LOW evidence YELLOWDihydronicotinamide riboside: synthesis from nicotinamide riboside chloride, purification and stability studies. ↗Zarei A et al.. Dihydronicotinamide riboside: synthesis from nicotinamide riboside chloride, purification and stability studies.. RSC Adv. 2021. PMID:35479370.PMID 35479370 ↗Journal RSC AdvYear 2021Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/35479370/
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 NR (Nicotinamide Riboside). 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 NR (Nicotinamide Riboside)
A score of 5.0 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.