Safety Profile
Known Safety Concerns
- Hepatotoxicity at doses above 3 g per day -- liver enzyme elevations
- Insulin resistance and blood sugar worsening at high doses
- No flushing (unlike niacin) but same hepatic risk at high doses
- UL applies as with niacin -- 35 mg per day for the no-flush form at the tolerable upper level
Contraindications
- Hepatotoxicity at doses above 3 g per day -- liver enzyme elevations
- Insulin resistance and blood sugar worsening at high doses
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
Niacinamide (nicotinamide) is the amide form of vitamin B3 that does NOT cause the flushing associated with nicotinic acid. Widely used in skincare and supplements. At high doses above 3 g per day, hepatotoxicity risk emerges — liver enzyme elevations have been reported. It also causes insulin resistance at high doses and may worsen blood sugar control. Less cardiovascular risk than niacin but similar hepatic risk at pharmacological doses.
Biological and Chemical Classification
- Scientific Name
- Nicotinamide
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: Vitamin
- Evidence consistency: High consistency across studies (100%)
- Hepatotoxicity at doses above 3 g per day -- liver enzyme elevations
- Insulin resistance and blood sugar worsening at high doses
- No flushing (unlike niacin) but same hepatic risk at high doses
- UL applies as with niacin -- 35 mg per day for the no-flush form at the tolerable upper level
The available scientific evidence for Vitamin B3 (Niacinamide) 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, 07:56
Evidence Distribution
-
Observational / other LOW evidence YELLOWEfficacy and Safety of a Topical Nicotinamide Adenine Dinucleotide Skinbooster for the Treatment of Melasma. ↗Yi KH et al.. Efficacy and Safety of a Topical Nicotinamide Adenine Dinucleotide Skinbooster for the Treatment of Melasma.. Aesthetic Plast Surg. 2026. PMID:41870519.PMID 41870519 ↗Journal Aesthetic Plast SurgYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41870519/
-
Observational / other LOW evidence YELLOWAuthor Response: Letter in Response to the Article: Utility of Extracellular Nicotinamide Phosphoribosyl Transferase as a Novel Biomarker in Predicting Early Severe… ↗Rao S et al.. Author Response: Letter in Response to the Article: Utility of Extracellular Nicotinamide Phosphoribosyl Transferase as a Novel Biomarker in Predicting Early Severe Organ Dysfunction and Mortality in Acute Respiratory Distress Syndrome: A Prospective Observational Study.. Indian J Crit Care Med. 2026. PMID:41868083.PMID 41868083 ↗Journal Indian J Crit Care MedYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41868083/
-
Observational / other LOW evidence YELLOWLetter in Response to the Article: Utility of Extracellular Nicotinamide Phosphoribosyl Transferase as a Novel Biomarker in Predicting Early Severe Organ Dysfunction… ↗Ghatak T et al.. Letter in Response to the Article: Utility of Extracellular Nicotinamide Phosphoribosyl Transferase as a Novel Biomarker in Predicting Early Severe Organ Dysfunction and Mortality in Acute Respiratory Distress Syndrome: A Prospective Observational Study.. Indian J Crit Care Med. 2026. PMID:41868066.PMID 41868066 ↗Journal Indian J Crit Care MedYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41868066/
-
Observational / other LOW evidence YELLOWPANoptosis in Alzheimer's disease: The expanding landscape of programmed cell death mechanisms and therapeutic interventions. ↗Paidlewar M et al.. PANoptosis in Alzheimer's disease: The expanding landscape of programmed cell death mechanisms and therapeutic interventions.. Free Radic Biol Med. 2026. PMID:41864364.PMID 41864364 ↗Journal Free Radic Biol MedYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41864364/
-
Observational / other LOW evidence YELLOWA ketogenic diet reduces hepatic alcohol metabolism and alcohol consumption in rats. ↗Elvig SK et al.. A ketogenic diet reduces hepatic alcohol metabolism and alcohol consumption in rats.. Neuropsychopharmacology. 2026. PMID:41862734.PMID 41862734 ↗Journal NeuropsychopharmacologyYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41862734/
-
Observational / other LOW evidence YELLOWDLK, NMNAT2, and SARM1: Judge, Jury, and Executioner in Axon Degeneration. ↗Hinz FI et al.. DLK, NMNAT2, and SARM1: Judge, Jury, and Executioner in Axon Degeneration.. Annu Rev Biochem. 2026. PMID:41861244.PMID 41861244 ↗Journal Annu Rev BiochemYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41861244/
-
Observational / other LOW evidence YELLOWEvaluation of effectiveness of oleanolic acid in rat testicular ischemia-reperfusion injury model. ↗Wei SM et al.. Evaluation of effectiveness of oleanolic acid in rat testicular ischemia-reperfusion injury model.. Pol J Vet Sci. 2026. PMID:41859995.PMID 41859995 ↗Journal Pol J Vet SciYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41859995/
-
Observational / other LOW evidence YELLOWThe NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation. ↗Berven H et al.. The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation.. iScience. 2026. PMID:41858901.PMID 41858901 ↗Journal iScienceYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41858901/
-
Observational / other LOW evidence YELLOWMolecular and cellular consequences of tumour-autonomous IL-6 signalling in intrahepatic cholangiocarcinoma. ↗Gehl V et al.. Molecular and cellular consequences of tumour-autonomous IL-6 signalling in intrahepatic cholangiocarcinoma.. Gut. 2026. PMID:41856523.PMID 41856523 ↗Journal GutYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41856523/
-
Observational / other LOW evidence YELLOWNicotinamide (Vitamin B3) Deficiency in Follicular Fluid of Patients With Ovarian Ageing. ↗Bocca C et al.. Nicotinamide (Vitamin B3) Deficiency in Follicular Fluid of Patients With Ovarian Ageing.. J Cell Mol Med. 2026. PMID:41853933.PMID 41853933 ↗Journal J Cell Mol MedYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41853933/
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 Vitamin B3 (Niacinamide). 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 Vitamin B3 (Niacinamide)
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.