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Niacinamide for Health & Longevity

Evidence Review created on 08/26/2026 using AI4L / Grok 4.6

Also known as: Nicotinamide, NAM, 3-Pyridinecarboxamide, Vitamin B3 Amide, Nicotinic Acid Amide

Motivation

Niacinamide is a form of vitamin B3. Unlike ordinary niacin, it does not cause flushing and does not lower blood fats. Cells convert it into a molecule used for energy and repair. Longevity-oriented adults meet it as an inexpensive oral supplement, a leave-on skin product, and a proposed way to lower new common non-melanoma skin cancers and to support the energy of the retina in glaucoma.

It was isolated to treat the niacin-deficiency disease of dermatitis, diarrhea, and dementia. A later year-long trial in people with prior skin cancers found fewer new common non-melanoma skin cancers at one gram per day, while a similar trial in organ-transplant recipients did not. That split, plus debate over whether high doses help or hinder enzymes involved in how cells handle stress, is why the compound sits in both dermatology practice and discussions of related vitamin B3 supplements.

This review examines the human evidence on niacinamide for health and longevity, how it differs from related vitamin B3 forms, and the practical conditions under which people use it.

Benefits - Risks - Protocol - Conclusion

High-level overviews of niacinamide as a vitamin B3 amide, a NAD+ (nicotinamide adenine dinucleotide, the cell’s energy-and-repair cofactor) precursor, and a dermatologic agent.

  • NAD+ - Rhonda Patrick

    Maps niacinamide as a NAD+ precursor and why precursor choice changes longevity-enzyme debates.

  • NMN vs. NAD vs. NR With Dr. Brad Stanfield - Steve Hill

    Compares niacinamide with nicotinic acid, nicotinamide riboside, and NMN (nicotinamide mononucleotide) as NAD+ precursors, emphasizing human trials over mouse claims.

  • Nicotinamide and the skin - Chen & Damian, 2014

    Dermatology narrative review of oral and topical niacinamide for DNA repair, actinic keratoses (sun-damaged precancerous lesions), aging skin, acne, and blistering disease.

  • Possible Adverse Effects of High-Dose Nicotinamide: Mechanisms and Safety Assessment - Hwang & Song, 2020

    Reviews high-dose safety: DNA-repair-enzyme and sirtuin (NAD-dependent deacetylase) inhibition, methyl demand, and megadose risk.

Fewer than five qualifying high-level sources were listed; the list was not padded with marginally relevant NAD-booster marketing. No dedicated niacinamide pages were found on Peter Attia, Andrew Huberman, or Chris Kresser sites. Life Extension magazine features on nicotinamide and skin cancer did not resolve to live article URLs.

Grokipedia

  • Niacinamide

    Site overview of niacinamide as a vitamin B3 form used in skincare for barrier support, redness, texture, and pigmentation.

Examine

ConsumerLab

ConsumerLab.com has a B Vitamin Supplements Review that includes niacin/niacinamide product testing, but the full report is members-only and no public page satisfied Section 5.

Systematic Reviews

Systematic reviews and meta-analyses of oral or topical nicotinamide for skin-cancer chemoprevention, adverse effects, dialysis phosphate control, and glaucoma.

Mechanism of Action

Niacinamide is the amide form of vitamin B3. Cells convert it to NAD+ (nicotinamide adenine dinucleotide, a cofactor for energy metabolism and DNA repair) through NAMPT (nicotinamide phosphoribosyltransferase, the rate-limiting salvage enzyme) and then NMNAT (nicotinamide mononucleotide adenylyltransferase, which finishes NAD+ assembly). NAD+ supports redox metabolism and is the substrate for sirtuins (NAD-dependent deacetylases linked to metabolic and longevity pathways) and PARPs (poly(ADP-ribose) polymerases, DNA-repair enzymes that consume NAD+). Ultraviolet (UV) stress depletes cutaneous NAD+; restoring it can enhance repair of UV photolesions and blunt UV immunosuppression.

Competing accounts matter at high dose. In vitro, niacinamide is a product inhibitor of SIRT1 (sirtuin 1) and PARPs, which raised the concern that megadoses could blunt longevity-linked deacetylation. In cells, administered niacinamide is rapidly converted to NAD+, so net sirtuin activity can rise after a brief inhibitory window. A third fate is methylation by NNMT (nicotinamide N-methyltransferase) to 1-methylnicotinamide, which consumes SAM (S-adenosylmethionine, the primary methyl donor) and can perturb methyl metabolism with chronic high intake. Unlike nicotinic acid, niacinamide does not activate GPR109A (the niacin flush receptor) and does not reliably lower lipids.

Plasma half-life is short (about 1–4 hours at usual supplemental doses) and lengthens as methylation and urinary pyridone excretion saturate at gram doses. Distribution is wide, including skin and neural tissue. Metabolism is via NAMPT salvage and NNMT methylation, not a primary cytochrome P450 pathway. Selectivity is low: it is a vitamin precursor, not a receptor-targeted drug.

Historical Context & Evolution

Niacinamide was identified in the 1930s as the pellagra-preventing amide of nicotinic acid. Pellagra (the niacin-deficiency disease of dermatitis, diarrhea, and dementia) responded to either form; the amide avoided flushing. For decades it was treated as a quiet vitamin, not a longevity candidate.

High-dose use entered endocrinology as a proposed shield for pancreatic beta cells. Animal work and small human series led to the European Nicotinamide Diabetes Intervention Trial, which found no delay of type 1 diabetes in antibody-positive relatives (Gale et al., 2004).

Dermatology then drove the modern indication. Work from the Damian and Halliday group showed that niacinamide supports ultraviolet (UV) DNA repair in keratinocytes (the main cells of the outer skin) (Surjana et al., 2013). The publicly funded ONTRAC trial (2015) reported fewer new keratinocyte cancers (basal- and squamous-cell skin cancers) in high-risk immunocompetent adults at 500 mg twice daily (Chen et al., 2015). ONTRANS (2023) found no such reduction in solid-organ transplant recipients (Allen et al., 2023). NAD-longevity interest then focused public attention on nicotinamide riboside and nicotinamide mononucleotide, in part because niacinamide can inhibit sirtuins in vitro. Glaucoma groups (Williams, Crowston, Hui) later tested high-dose oral niacinamide for retinal ganglion energy. A 2025 Veterans Affairs cohort again associated 500 mg twice daily with fewer subsequent skin cancers, strongest when started after a first cancer (Breglio et al., 2025). Scientific opinion has shifted with each large trial; it has not settled on a final chemoprevention or longevity role.

Expected Benefits

High 🟩 🟩 🟩

Keratinocyte Skin-Cancer Chemoprevention ⚠️ Conflicted

A 386-person phase 3 trial found 23% fewer new keratinocyte cancers at 1 g/day in immunocompetent high-risk adults (Chen et al., 2015). Meta-analyses disagree: a five-trial pool was positive (Mainville et al., 2022); a pool that included transplant recipients was not (Tosti et al., 2023). The dedicated transplant trial found no reduction (Allen et al., 2023). A Veterans Affairs cohort reported 14% fewer later cancers, 54% after a first cancer (Breglio et al., 2025). Net reading: a signal in immunocompetent high-risk adults, not after transplant.

Magnitude: ONTRAC: 23% lower new keratinocyte-cancer rate at 12 months (95% CI (confidence interval) 4–38); VA cohort: 14% overall and 54% after a first cancer; Tosti pooled RR (relative risk) 0.82 (95% CI 0.61–1.12, not significant).

Medium 🟩 🟩

Actinic Keratoses

ONTRAC found 11–20% fewer actinic keratoses (sun-damaged precancerous lesions) at 3–12 months versus placebo (Chen et al., 2015). The proposed mechanism is restored NAD+-dependent DNA repair and reduced UV immunosuppression (Surjana et al., 2013). ONTRANS did not reduce actinic keratoses in transplant recipients (Allen et al., 2023). The finding is a secondary endpoint in the landmark immunocompetent trial, not a standalone longevity outcome.

Magnitude: 13% fewer actinic keratoses at 12 months in ONTRAC (P = 0.001); no reduction in ONTRANS.

Topical Appearance of Aging Facial Skin

Leave-on 5% niacinamide improved wrinkling, yellowing, red blotchiness, and hyperpigmented spots versus vehicle in randomized cosmetic trials (Bissett et al., 2004; Bissett et al., 2005). Mechanisms include barrier-lipid synthesis, reduced melanosome transfer, and anti-inflammatory effects. These are appearance endpoints in industry-sponsored studies, not validated healthspan surrogates.

Magnitude: Directionally improved wrinkle and hyperpigmentation scores over 8–12 weeks versus vehicle; the literature report no single pooled effect size across trials.

Low 🟩

Oral Skin-Barrier Function

A randomized analysis nested in the ONTRAC program found oral nicotinamide reduced transepidermal water loss (insensible water loss through skin, a barrier measure) (Chen et al., 2016). The dataset is a secondary letter from one trial program, not an independent outcome series.

Magnitude: Direction of reduced transepidermal water loss on 500 mg twice daily; the literature report no widely replicated numeric effect size.

Acne Lesion Reduction

Topical nicotinamide has been tested for inflammatory acne in randomized dermatology trials. A Cochrane review found only very-low-certainty evidence versus vehicle (Liu et al., 2020). This is a skin-appearance outcome, not a longevity endpoint.

Magnitude: Direction of fewer inflammatory lesions in small topical trials; the literature report no widely replicated pooled effect size for oral niacinamide.

Speculative 🟨

Inner Retinal Function in Glaucoma

A crossover trial found a larger electrical-retina response at gram doses (Hui et al., 2020). Field mean-deviation did not improve in a three-trial review (Sherratt-Mayhew et al., 2026). Unvalidated electrical measure only.

Systemic NAD Restoration for Longevity

Niacinamide can raise NAD+ in cells after a brief SIRT1-inhibitory window (Hwang & Song, 2017). No controlled human study shows lifespan or healthspan gain. The basis is mechanistic only.

Benefit-Modifying Factors

  • Prior keratinocyte-cancer burden: Chemoprevention signal is strongest in immunocompetent adults after a first skin cancer and weaker after many subsequent cancers (Breglio et al., 2025).
  • Immune status: Solid-organ transplant recipients did not gain keratinocyte-cancer reduction in ONTRANS, unlike immunocompetent ONTRAC participants (Allen et al., 2023).
  • Baseline NAD and UV load: Cutaneous NAD depletion from UV and age is the mechanistic rationale; people with high cumulative sun damage are the studied benefit population (Surjana et al., 2013).
  • Sex: Pivotal skin-cancer and glaucoma trials enrolled mixed sexes without a replicated sex-specific efficacy split; women were a small minority in the Veterans Affairs cohort.
  • Age: ONTRAC and the Veterans Affairs cohort were older adults (mean ages in the mid-to-late 70s in the VA set); pediatric efficacy for longevity endpoints is not established.
  • NNMT and methylation status: High NNMT activity shunts niacinamide into 1-methylnicotinamide and consumes SAM, which may blunt NAD salvage and raise methyl demand (Hwang & Song, 2020).

Potential Risks & Side Effects

High 🟥 🟥 🟥

Gastrointestinal Upset at Gram Doses

Nausea, diarrhea, and abdominal discomfort become common as oral doses reach 1.5–3 g/day in glaucoma protocols (Young & Gazzard, 2025; Hui et al., 2020). A chemoprevention meta-analysis found more digestive adverse events versus control (Mainville et al., 2022). At 1 g/day, adverse events matched placebo (Chen et al., 2015). Effects usually reverse with dose reduction.

Magnitude: Digestive adverse events rise at 1.5–3 g/day glaucoma doses and were more common than control in chemoprevention meta-analysis; the literature report no outcome figure for a pooled digestive-event rate at 1 g/day.

Thrombocytopenia in Dialysis and High-Dose Use

Dialysis trials of nicotinamide for phosphate control reported a higher adverse-event rate than control, including thrombocytopenia (low platelet count) (Zhang et al., 2018; Hussain et al., 2020). The WebMD niacinamide monograph lists easy bruising and increased bleeding as common high-dose effects. This is a disease-population, high-dose finding, not a demonstrated risk at 1 g/day in people with normal marrow and kidney function.

Magnitude: Zhang meta-analysis: adverse-event OR (odds ratio) 3.99 (95% CI 1.94–8.23); thrombocytopenia OR 49.00 (95% CI 2.68–897.36) in dialysis trials.

Medium 🟥 🟥

Hepatotoxicity at Very High Doses

Reversible liver-enzyme elevations and rare hepatotoxicity are documented at adult doses above about 3 g/day (Knip et al., 2000). Young and Gazzard note liver dysfunction among dose-dependent effects and that routine monitoring may not be indicated under 1,500 mg/day (Young & Gazzard, 2025). Timed-release nicotinic acid is the more hepatotoxic B3 form; niacinamide is cleaner but not exempt at megadoses.

Magnitude: Toxic potential is described above 3 g/day, with infrequent enzyme abnormalities at diabetes-prevention doses; the literature report no outcome figure for a pooled hepatotoxicity rate at 1 g/day.

Low 🟥

Flushing and Vasodilation

Flushing is characteristic of nicotinic acid via GPR109A, not of niacinamide, but overviews still list occasional flush-type symptoms with oral nicotinamide (Young & Gazzard, 2025). Confusing the two forms is a common sourcing error.

Magnitude: Incidence is substantially lower than with nicotinic acid; the literature report no pooled flush rate for niacinamide at 1 g/day.

Minor Insulin-Resistance Signal

A safety review noted inconsistent glucose kinetics and minor insulin resistance in some high-dose series (Knip et al., 2000). The large diabetes-prevention trial found no effect on first-phase insulin secretion (Gale et al., 2004).

Magnitude: Direction of minor insulin resistance in some high-dose series; the literature report no consistent glycemic effect size in healthy adults.

Speculative 🟨

Sirtuin Inhibition and Longevity Trade-Off

In vitro SIRT1 inhibition (Bitterman et al., 2002) can give way to higher NAD+ and sirtuin activity in cells (Hwang & Song, 2017). No human lifespan harm is shown. Mechanistic only.

Methylation-Sink and Epigenetic Change

High-dose niacinamide increases NNMT flux and 1-methylnicotinamide, consuming SAM (Hwang & Song, 2020). Human epigenetic harm at 1 g/day is not shown. The basis is mechanistic.

Risk-Modifying Factors

  • Dose: Adverse events rise above about 1.5 g/day; Knip et al., 2000 flagged toxic potential above 3 g/day; Young & Gazzard, 2025 suggested monitoring is less clearly indicated under 1,500 mg/day.
  • Kidney failure and dialysis: Phosphate-lowering trials in hemodialysis show thrombocytopenia and higher adverse-event rates; eGFR (estimated glomerular filtration rate) below 30 mL/min/1.73 m² was an exclusion in NAMinG.
  • Baseline liver enzymes: Pre-existing liver disease and AST or ALT (aspartate and alanine aminotransferase, liver enzymes) above 3× the upper limit of normal are exclusions in current high-dose glaucoma trials.
  • Sex: No replicated sex-specific adverse-event split; pregnancy and breastfeeding lack high-dose human data (WebMD).
  • Age: Older adults dominate chemoprevention cohorts; they also have more polypharmacy and lower NAD, which changes both risk and putative benefit.
  • NNMT / methyl status: High NNMT or low methyl-donor status may amplify SAM consumption at gram doses (Hwang & Song, 2020).

Key Interactions & Contraindications

  • Other vitamin B3 forms (nicotinic acid, nicotinamide riboside, NMN (nicotinamide mononucleotide)): Caution — additive NAD+ load, methyl demand, and overlapping gut or liver risk (WebMD niacinamide monograph).
  • Isoniazid (and pyrazinamide): Caution — isoniazid interferes with niacin metabolism and can precipitate pellagra; NAMinG excluded concurrent isoniazid or pyrazinamide (NCT05405868).
  • Enzyme-inducing anticonvulsants (carbamazepine, phenobarbital, primidone): Caution — excluded from NAMinG; potential for altered vitamin B3 handling and additive liver strain.
  • Hepatotoxic over-the-counter agents (high-dose acetaminophen, heavy alcohol): Caution — additive liver injury risk at gram niacinamide doses; Young & Gazzard, 2025 list liver dysfunction among dose-dependent effects.
  • Anticoagulants and antiplatelets (warfarin, apixaban, aspirin): Monitor — high-dose niacinamide is linked to bruising and bleeding in monographs; dialysis trials reported thrombocytopenia (WebMD niacinamide monograph).
  • Methyl-donor supplements (folate, vitamin B12, trimethylglycine): Potentiating for methylation support — may offset NNMT-driven SAM consumption at high niacinamide doses; not an adverse interaction.
  • Tetracyclines (doxycycline, minocycline): Monitor — used with niacinamide in blistering-disease protocols; additive GI (gastrointestinal) effects.

Populations who should avoid Niacinamide:

Risk Mitigation Strategies

  • Chemoprevention-dose ceiling: The 500 mg twice-daily regimen used in ONTRAC had placebo-like adverse events, limiting gut and liver risk versus 3 g glaucoma regimens.
  • Split doses with food: Short half-life supports twice-daily dosing; food reduces nausea reported at gram intakes.
  • Baseline and follow-up liver enzymes: Mitigates missed hepatotoxicity if intake exceeds about 1.5 g/day or liver disease is present.
  • Platelet checks in chronic kidney disease or dialysis: Mitigates thrombocytopenia documented in hemodialysis nicotinamide trials.
  • Form substitution: Keeping the amide, not nicotinic acid, mitigates flush, GPR109A (niacin-flush receptor) effects, and timed-release-niacin liver injury from form mix-ups.
  • Methyl-donor intake at gram doses: Folate, vitamin B12, and choline-rich intake offset NNMT-driven SAM consumption.
  • Stop triggers: Jaundice, dark urine, or unusual bruising flag liver injury or low platelets and were stopping rules in high-dose trials.

Therapeutic Protocol

  • Chemoprevention dose used by dermatology trialists: Damian/Chen ONTRAC protocol is 500 mg orally twice daily in immunocompetent adults with prior keratinocyte cancers (Chen et al., 2015).
  • Competing NAD-precursor approach: Longevity clinics often prefer nicotinamide riboside or NMN (nicotinamide mononucleotide) over niacinamide because of in-vitro SIRT1 inhibition; Hwang & Song, 2017 argue cellular conversion can later raise sirtuin activity.
  • Investigational glaucoma dose: Hui and ongoing NAMinG/TGNT protocols use 1.5 g daily for 6 weeks then 3.0 g daily (Hui et al., 2020; NCT05405868).
  • Topical dermatology: Leave-on 4–5% niacinamide is the concentration in Bissett appearance trials; 10% products exist without matching outcome trials.
  • Time of day: Split morning and evening; short plasma half-life (about 1–4 hours at usual doses) argues against a single daily bolus at gram intakes.
  • Single versus split: Split twice daily matches ONTRAC and reduces peak-related nausea versus one large dose.
  • Genetics: NNMT and NAMPT variants can shift methylation versus salvage; MTHFR (methylenetetrahydrofolate reductase, a folate-processing enzyme) status is a methyl-budget consideration, not a validated dose algorithm.
  • Sex: No established sex-specific oral dose; pregnancy megadoses remain untested.
  • Age: Older adults are the chemoprevention evidence base; trialists used 500 mg twice daily rather than 3 g when the studied goal was skin-cancer risk, not glaucoma research.
  • Baseline biomarkers: Prior keratinocyte-cancer count, liver enzymes, platelets if CKD (chronic kidney disease), and homocysteine if using gram doses.
  • Pre-existing disease: Liver disease, eGFR <30, and transplant immunosuppression change both efficacy (ONTRANS null) and safety.

Discontinuation & Cycling

  • Duration: Chemoprevention in ONTRAC was 12 months; benefit was not evident in the 6 months after stopping, so use is ongoing while the indication remains, not a one-time course.
  • Withdrawal: No nicotinamide withdrawal syndrome is described in Knip et al., 2000, ONTRAC, or Young & Gazzard, 2025.
  • Taper: Abrupt stop is the trial pattern; a taper is not required at 1 g/day.
  • Cycling: No evidence that cycling preserves efficacy; NAD salvage does not show the receptor downregulation that motivates stimulant cycling.
  • After stopping: Skin-cancer rate in ONTRAC returned toward placebo after discontinuation, so any chemoprevention effect appears use-dependent.

Sourcing and Quality

  • Form: The label should read niacinamide or nicotinamide, not nicotinic acid, niacin, inositol hexanicotinate, nicotinamide riboside, or NMN.
  • Third-party testing: USP Verified, NSF, or ConsumerLab-tested products address the B-vitamin label failures ConsumerLab reports in this category.
  • Dose accuracy: Chemoprevention evidence is 500 mg twice daily of the amide; many “NAD booster” blends substitute other B3 forms.
  • Topical vehicles: Leave-on serums at 4–5% match appearance trials; rinse-off cleansers do not.
  • Reputable supply: USP-verified commodity niacinamide from major supplement lines is widely sold; compounding is unnecessary for oral 500 mg units.

Practical Considerations

  • Time to effect: Actinic-keratosis counts moved by 3 months in ONTRAC; keratinocyte-cancer reduction was a 12-month endpoint; topical appearance changes are typically scored at 8–12 weeks.
  • Common pitfalls: Confusing niacinamide with flushing niacin; stacking several NAD precursors; stopping sun protection because of chemoprevention use; assuming ONTRANS-null transplant data apply to immunocompetent adults, or the reverse.
  • Regulatory status: Sold as a dietary supplement and topical cosmetic in the United States; not FDA-approved to prevent skin cancer. ONTRAC used an Australian registry number, not an FDA indication.
  • Cost versus other NAD precursors: Niacinamide is a low-cost commodity relative to nicotinamide riboside and NMN. Insurers and health systems have no documented incentive to prefer one precursor, so payer-driven guideline bias is not established.

Interaction with Foundational Habits

  • Sleep: Direct — none established; niacinamide is not a sedative at chemoprevention doses and was not linked to sleep disruption in ONTRAC adverse-event tables.
  • Nutrition: Potentiating — adequate protein and tryptophan feed de novo NAD synthesis; at gram doses, folate, B12, choline, and betaine support the methyl groups NNMT consumes.
  • Exercise: Potentiating — endurance exercise upregulates NAMPT and NAD salvage; niacinamide is not shown to blunt hypertrophy. Timing relative to workouts is not established.
  • Stress management: Indirect — psychological and inflammatory stress raise NAD+ consumption via PARP and CD38 (an NAD-consuming glycohydrolase); niacinamide does not replace sleep or load management.

Monitoring Protocol & Defining Success

Before chemoprevention or gram-level dosing, baseline tests are liver enzymes; a complete blood count if kidney disease is present; fasting glucose or HbA1c (glycated hemoglobin, a three-month glucose average) at 1.5–3 g/day; and homocysteine if methyl demand is a concern. A skin examination documents prior keratinocyte cancers and actinic keratoses. Whole-blood NAD+ is optional, with no consensus target.

Ongoing labs at 3 months, then every 6–12 months at 1 g/day if enzymes are stable, and sooner above 1.5 g/day, with liver disease, or on dialysis. Dermatology review every 3–12 months if chemoprevention is the goal. Success is fewer new cancers or actinic keratoses versus the person’s recent rate, stable enzymes and platelets, and tolerable digestion.

Biomarker Optimal Functional Range Why Measure It? Context/Notes
ALT / AST Often <25 U/L in functional practice; stop or reduce if >3× ULN Detect hepatotoxicity at high dose Alanine and aspartate aminotransferase (liver enzymes). Conventional upper limit of normal (ULN) ~40 U/L; NAMinG excludes >3× ULN; fasting not required
Platelets Track change from personal baseline; conventional 150–400 ×10⁹/L Dialysis trials reported thrombocytopenia Pair with complete blood count if eGFR is reduced; bruising is a clinical flag
Homocysteine Functional often <8 μmol/L; conventional <15 Proxy for methyl-donor strain from NNMT Fasting preferred; interpret with B12 and folate
HbA1c Functional often 4.8–5.3%; conventional <5.7% High-dose series reported minor insulin-resistance signals NAMinG schedules glucose/HbA1c with liver enzymes
Whole-blood NAD+ No established target; track change from own baseline Confirms precursor engagement Not a validated healthspan surrogate; labs vary by method
Skin examination Individual’s new keratinocyte-cancer and AK counts The ONTRAC clinical endpoint Actinic keratosis (AK) counts; every 3–12 months if chemoprevention is the goal
  • Energy and gut tolerance
  • New or changing skin lesions
  • Easy bruising or prolonged bleeding
  • Visual function if glaucoma is the indication (fields, not NAD+ kits)

Emerging Research

  • NAMinG phase 3 glaucoma: NCT05405868 randomizes recently diagnosed open-angle glaucoma to nicotinamide (1.5 g then 3.0 g) versus placebo for 27 months; primary endpoint is visual-field mean deviation (n = 496, recruiting).
  • The Glaucoma Nicotinamide Trial: NCT05275738 tests 1.5 then 3.0 g nicotinamide versus placebo over two years for field progression (n = 660, recruiting), including a newly diagnosed untreated cohort.
  • Nicotinamide plus pyruvate: NCT05695027 is a phase 2/3 randomized study in primary open-angle glaucoma (n = 250, active, not recruiting).
  • VA chemoprevention cohort: Breglio et al., 2025 associated 500 mg twice daily with fewer subsequent skin cancers, strongest after a first cancer — observational, not randomized.
  • Early Alzheimer disease: Grill et al., 2025 found 3 g/day nicotinamide for 48 weeks did not change cerebrospinal-fluid phosphorylated tau versus placebo (NCT03061474).
  • Topical transplant chemoprevention: NCT07286318 is an early randomized trial of topical 5% niacinamide for skin-cancer prevention in organ-transplant recipients (n = 20, recruiting).

Conclusion

Niacinamide is a non-flushing form of vitamin B3 that cells use to rebuild a core energy and repair molecule. For longevity-oriented adults, the human signal that holds up is not lifespan extension. It is a reduction in new common non-melanoma skin cancers among people with a working immune system and prior skin cancers at one gram per day, a finding that disappeared in organ-transplant recipients and that combined trial analyses do not all confirm. Topical use can change the look of sun-aged facial skin. High-dose oral use can improve an electrical retinal signal in glaucoma, without yet proving slower field loss.

The main practical risks at one gram per day look close to placebo in the large skin-cancer trial. Gut upset, low platelets in dialysis, and liver-enzyme changes appear as the dose climbs toward three grams. Findings that high doses can block certain enzymes, and extra methyl-group use, remain lab-only cautions, not shown as human harms at one-gram doses. Other B3 forms are not interchangeable: nicotinic acid flushes and affects lipids; other B3 supplements are different compounds.

The evidence base is a mix of one large positive prevention trial, one large transplant trial that found no reduction, conflicting combined analyses, a large records cohort, and small glaucoma and cosmetic studies. Industry incentives exist on the skincare side; the large cancer trials were public-grant work. Uncertainty is the honest summary: useful in a narrow high-risk skin setting, unproven as a general longevity drug, and dose-limited by gut and liver, not flushing.

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