Niacinamide (Nicotinamide)
Vitamin B3 amide
Versatile B3 amide for barrier, tone, oil & skin-cancer defense
Evidence tier
Moderate
Research weight
Citations
15 verified / 15
Classification
Vitamin
❝
What the evidence says. Several controlled trials; effects real but modest or context-dependent.
What is Niacinamide (Nicotinamide)?
Niacinamide (Nicotinamide) (Vitamin B3 amide) is a vitamin used for reduces hyperpigmentation & uneven tone. NutriDex grades the human evidence as Moderate. Niacinamide is the amide form of vitamin B3 that replenishes cellular NAD+, supporting DNA repair, barrier (ceramide) synthesis, sebum regulation, and reduced melanosome transfer. In the landmark ONTRAC RCT (Chen 2015, NEJM), oral nicotinamide 500 mg twice daily cut new non-melanoma skin cancers ~23% in immunocompetent high-risk patients. The later phase-3 ONTRANS trial in organ-transplant recipients was negative, so oral chemoprevention benefit appears limited to immunocompetent skin. Topical niacinamide (2–5%) is separately supported for hyperpigmentation, fine lines, redness, barrier function and oiliness, though effects are modest.
Purported Benefits
✓Reduces hyperpigmentation & uneven tone
✓Strengthens barrier, lowers water loss
✓Curbs sebum and pore size
✓Aids UV DNA repair in high-risk skin
Evidence by outcome
The same supplement can be well-proven for one use and unproven for another — here is the human evidence graded outcome by outcome.
| Outcome | Evidence | Effect | Studies |
|---|---|---|---|
| Oral chemoprevention of non-melanoma skin cancer (immunocompetent)ONTRAC RCT cut NMSC ~23% in high-risk immunocompetent skin, but a 2024 meta of 4 RCTs found no significant overall reduction. | Mixed | ↔ mixed · small | 3 |
| Skin-cancer prevention in transplant/immunosuppressedPhase-3 ONTRANS RCT (158 transplant recipients) showed no reduction in keratinocyte cancers (RR 1.0). | Moderate | — no effect · negligible | 1 |
| Topical: hyperpigmentation/melasmaMultiple RCTs show topical niacinamide improves melasma comparably to but numerically below hydroquinone, with better tolerability. | Moderate | ↑ benefit · small | 4 |
| Topical: barrier, wrinkles, redness, textureReview of 4-5% topical reports improved wrinkles, texture and redness over 8-12 wk; mostly small studies, effects modest. | Preliminary | ↑ benefit · small | 1 |
| Type 1 diabetes prevention (oral)Landmark ENDIT RCT (552 high-risk relatives, 5 yr) found no prevention of type 1 diabetes (HR 1.01). | Strong | — no effect · negligible | 1 |
| NAD+ precursors (NMN/NR) for metabolism/muscle/cognitionMeta-analyses show NMN/NR raise NAD+ but yield no benefit on glucose, lipids, muscle or cognition; raised NAD+ != outcomes. | Moderate | — no effect · negligible | 3 |
| Hyperphosphatemia in hemodialysis (oral)NOPHOS RCT (722 pts) lowered phosphate at 24 wk but effect lost by 52 wk with excess harms; unfavorable benefit:risk. | Moderate | ↔ mixed · small | 1 |
Dosing & Compounds
Typical Dose
Oral: 500 mg twice daily (chemoprevention). Topical: 2–5% in serums/creams.
Active Compounds
Safety & Cautions
Well tolerated and, unlike niacin (nicotinic acid), does NOT cause flushing — don't confuse the two. No notable adverse-event excess at 1 g/day in the year-long ONTRAC trial; benefit fades after stopping. Topical 2–5% rarely causes mild irritation. Educational only — always check with your doctor or pharmacist before combining Niacinamide (Nicotinamide) with any medicine.
Key Studies ★ 15 studies
meta-analysis
Mohammadi 2024 (Systematic Review & Meta-Analysis)
✓ PubMed
Pooling 4 RCTs of oral nicotinamide for keratinocyte cancer prevention found no significant reduction in overall non-melanoma skin cancer (RR 0.82, 95% CI 0.61-1.12), SCC (RR 0.81) or BCC (RR 0.88), concluding evidence is insufficient that it meaningfully reduces skin cancers.
meta-analysis
Liao 2025 (Systematic Review & Meta-Analysis of RCTs)
✓ PubMed
Across 12 RCTs (513 adults), oral nicotinamide mononucleotide (NMN) raised blood NAD+ levels but produced no significant improvement in fasting glucose, insulin, HbA1c, HOMA-IR or lipid profile.
meta-analysis
Wang 2025 (Systematic Review & Meta-Analysis of RCTs)
✓ PubMed
Pooling 10 RCTs (6 NMN, 4 NR; ~230 adults aged >60) found no significant effect of NMN or NR on skeletal muscle index, handgrip strength, gait speed or chair-stand performance, not supporting their use to preserve muscle.
meta-analysis
Mainville 2022 (Systematic Review & Meta-Analysis)
✓ Full text
A pooled analysis of nicotinamide trials reported reductions in actinic keratoses and non-melanoma skin cancers with oral nicotinamide while finding adverse events to be rare, supporting a favorable safety profile.
Meta-analysis
Mainville et al. skin-cancer meta-analysis 2022
✓ PubMed
Systematic review and meta-analysis of nicotinamide for skin cancer and actinic keratosis chemoprophylaxis reported a reduction in nonmelanoma skin cancers with oral nicotinamide and a favorable adverse-event profile comparable to placebo, supporting tolerability while noting limited trial numbers.
RCT
Allen 2023 (ONTRANS, Phase 3 RCT)
✓ PubMed
In 158 immunosuppressed organ-transplant recipients, nicotinamide 500 mg BID for 12 months did NOT reduce keratinocyte cancers (rate ratio 1.0, P=0.96).
rct
Brakedal 2024 (Pilot RCT)
✓ PubMed
In a randomized placebo-controlled pilot of 20 older adults with mild cognitive impairment, nicotinamide riboside escalated to 1 g/day for 10 weeks left MoCA and other neurocognitive measures stable, showing no cognitive benefit.
RCT
Ketteler 2023 (NOPHOS, Phase 3 RCT)
✓ PubMed
In 722 hemodialysis patients with hyperphosphatemia (539 nicotinamide vs 183 placebo), modified-release nicotinamide added to phosphate binders lowered serum phosphate at week 24 (5.40 vs 5.79 mg/dL, P<0.001) but the effect was lost by week 52, and excess diarrhea, thrombocytopenia, anemia and herpes zoster gave an unfavorable benefit:risk ratio not supporting routine use.
RCT
Marçon et al. 2024
✓ Full text
In a double-blind RCT (n=49), topical nicotinamide 10% (with magnesium ascorbyl phosphate 5% + hyaluronic acid 5%) reduced mMASI by 32% (95% CI 23-41%) at day 60 versus 43% (95% CI 34-52%) for hydroquinone 4%, i.e. effective for facial melasma but numerically inferior to hydroquinone.
RCT
Hesseler & Shyam 2024 (melasma RCTs)
✓ Source
Double-blind RCT (n=99, conducted 2023-2024) found niosomal and conventional tranexamic acid/niacinamide creams produced significant reductions in melanin index and mMASI comparable to hydroquinone 4% over 3 months in melasma patients.
Guideline
NIH Office of Dietary Supplements (Niacin Fact Sheet, Authoritative Body)
✓ Source
The NIH ODS states the Tolerable Upper Intake Level for niacin in adults is 35 mg/day (based on flushing), and warns that high supplemental nicotinamide can cause nausea, vomiting and signs of liver toxicity at intakes around 3,000 mg/day.
RCT
Chen 2015 (ONTRAC, Phase 3 RCT)
✓ PubMed
In 386 immunocompetent patients with ≥2 prior NMSCs, oral nicotinamide 500 mg BID for 12 months lowered new non-melanoma skin cancers by 23% (P=0.02) and reduced actinic keratoses.
RCT
Navarrete-Solis 2011 (Double-Blind RCT)
✓ PubMed
In 27 women with melasma, topical niacinamide 4% produced good-to-excellent improvement in 44% (vs 55% with hydroquinone 4%) with no significant colorimetric difference between agents but fewer adverse effects (18% vs 29%), supporting niacinamide as a better-tolerated alternative.
RCT
Gale 2004 (ENDIT, Landmark RCT, The Lancet)
✓ PubMed
In 552 islet-cell-antibody-positive first-degree relatives at high risk of type 1 diabetes, 5 years of oral modified-release nicotinamide (1.2 g/m2) did not prevent diabetes onset versus placebo (adjusted hazard ratio 1.01, 95% CI 0.73-1.38, P=0.97).
Review
Boo 2021 (Review)
✓ Full text
Topical niacinamide 4–5% improved wrinkles, texture, hyperpigmentation and redness over 8–12 weeks via slowed melanosome transfer and ceramide synthesis.