Nicotinamide
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Nicotinamide: From Vitamin B3 Deficiency (Pellagra) to Werner Syndrome
One-Sentence Summary
Nicotinamide is the amide form of vitamin B3, classically used to prevent and treat niacin deficiency (pellagra) and as an NAD+/NADP+ precursor in general nutrition. The TxGNN model predicts a potential application in Werner Syndrome, a rare premature-ageing disorder linked to cellular NAD+ depletion, with mechanistic and preclinical literature and one relevant RCT of a closely related NAD+-precursor compound currently supporting this direction — but no clinical trials of nicotinamide itself in this indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not specified in the MHRA licence data provided (no current UK marketing authorisation on file); classically indicated for prevention/treatment of niacin (vitamin B3) deficiency (pellagra) |
| Predicted New Indication | Werner Syndrome |
| TxGNN Prediction Score | 88.61% |
| Evidence Level | L3 |
| UK Market Status | Not Marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data for nicotinamide is not available in this evidence pack. Based on well-established pharmacology, nicotinamide is the amide form of vitamin B3 (niacin) and a direct metabolic precursor of nicotinamide adenine dinucleotide (NAD+) and NADP+ — essential cofactors for cellular redox reactions, DNA repair, and mitochondrial energy metabolism. Its role in preventing and treating niacin deficiency is long established, and mechanistically this NAD+-precursor function may extend to conditions characterised by pathological NAD+ depletion.
Werner Syndrome is caused by loss-of-function mutations in the WRN helicase gene, and the literature consistently shows this leads to impaired mitophagy, mitochondrial NAD+ depletion, and oxidative stress, driving the premature-ageing phenotype. This gives a biologically coherent rationale for NAD+ repletion strategies in Werner Syndrome, independent of nicotinamide’s original use.
An important caveat: the strongest clinical evidence identified (a double-blind, randomised, placebo-controlled crossover trial showing benefit in Werner Syndrome patients) used nicotinamide riboside (NR), a different NAD+-precursor molecule, not nicotinamide itself. The two compounds share a common downstream mechanism (NAD+ repletion) but are pharmacologically distinct, so this trial should be regarded as supportive but indirect evidence for nicotinamide.
Clinical Trial Evidence
Currently no related clinical trials registered for nicotinamide specifically in Werner Syndrome.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40459998 | 2025 | RCT (nicotinamide riboside, non-identical analogue) | Aging Cell | Double-blind, randomised, placebo-controlled crossover trial showing NAD+ supplementation benefits patients with Werner Syndrome; supports NAD+ repletion as a therapeutic strategy, though tested compound was nicotinamide riboside, not nicotinamide |
| 31754102 | 2019 | Preclinical/Mechanistic | Nature Communications | NAD+ augmentation restores mitophagy and limits accelerated ageing in Werner Syndrome patient samples and disease models |
| 40179319 | 2025 | Basic/Mechanistic | Aging | Demonstrates decreased mitochondrial NAD+ in WRN-deficient cells, linked to dysfunctional cell proliferation |
| 38184705 | 2024 | Basic/Mechanistic | Cell & Bioscience | WRN loss accelerates abnormal adipocyte metabolism, a further metabolic consequence of NAD+/WRN pathway disruption |
| 24757718 | 2014 | Basic/Mechanistic | Aging Cell | Werner protein downregulation induces a metabolic shift compromising redox homeostasis, reinforcing the NAD+/redox link |
| 34201700 | 2021 | Review | International Journal of Molecular Sciences | Reviews DNA damage-induced neurodegeneration in accelerated ageing syndromes including Werner Syndrome |
| 33353663 | 2021 | Review | Journal of Investigative Dermatology | Reviews skin abnormalities in disorders with DNA repair defects, premature ageing and mitochondrial dysfunction, including Werner Syndrome |
UK Market Information
Nicotinamide currently holds no MHRA marketing authorisation on file in this evidence pack (market status: Not Marketed, 0 licences recorded). No licensed product or approved-indication data is therefore available to summarise in this report.
Safety Considerations
Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
Note: this evidence pack flags the absence of MHRA warning/contraindication data as a blocking gap — this data must be obtained before any formal safety evaluation can proceed (see Conclusion below).
Conclusion and Next Steps
Decision: Hold
Rationale: There is a biologically plausible mechanism (NAD+ depletion in Werner Syndrome, correctable in principle by NAD+ precursors) and a supportive RCT — but that trial used nicotinamide riboside, not nicotinamide itself, so direct clinical evidence for this specific molecule is lacking. Combined with the absence of any UK marketing authorisation and a blocking gap in safety/label data, this candidate is not ready to advance past initial review.
To proceed, the following is needed:
- MHRA/SmPC safety data — key warnings and contraindications (currently missing, blocking)
- Full mechanism of action documentation for nicotinamide (currently missing)
- A direct clinical trial or at minimum pharmacokinetic bridging data comparing nicotinamide to nicotinamide riboside in Werner Syndrome
- Assessment of a UK regulatory/import pathway, given the drug currently has no marketing authorisation on file
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.