Vitamin

Vitamin B3

Niacin / Nicotinic acid

Evidence TierAWADA NOT PROHIBITED

tuneTypical Dose

500–2,000 mg nicotinic acid for lipid therapy, or 500 mg niacinamide BID (skin cancer prevention)

watchEffect Window

4–8 weeks for lipid profile shifts. 12 months for skin cancer chemoprevention assessment

check_circleCompliance

WADA NOT PROHIBITED

Overview

Clinical Summary

Vitamin B3 includes niacin and nicotinamide, supporting NAD-dependent energy metabolism. It is used to prevent pellagra, and pharmacologic niacin doses can modify lipids under clinical supervision.

Niacin prevents pellagra and supports cellular energy through NAD synthesis. Pharmacologic niacin lowers triglycerides and raises HDL, but side effects and limited outcome benefits reduce routine use. Nicotinamide has evidence for reducing certain nonmelanoma skin cancer recurrences in high-risk groups. Minority benefits include acne inflammation improvements in some contexts. Flushing and liver toxicity risk increase with higher doses, affecting net benefit.

Nicotinic acid inhibits hepatic DGAT2, reducing triglyceride synthesis and VLDL/LDL secretion while delaying HDL clearance. Niacinamide inhibits PARP, enhancing DNA repair in UV-damaged cells. Both forms serve as NAD+/NADP+ precursors.

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • Raises HDL and lowers LDL/TG (nicotinic acid)
  • Reduces non-melanoma skin cancer incidence (niacinamide)

Secondary Outcomes

  • NAD+ precursor for cellular energy and DNA repair
  • Niacin + statin does NOT reduce CV events beyond statin alone (negative finding)

Safety

Contraindications and Interactions

Contraindications

  • Active liver disease
  • Active peptic ulcer
  • Severe gout

Side effects

  • Niacin flush (warmth, redness, itching)
  • GI upset/nausea
  • Hepatotoxicity (sustained-release)
  • Hyperglycemia
  • Hyperuricemia

Interactions

  • Statins (no incremental CV benefit)
  • Diabetes medications (may worsen glycemic control)
  • Alcohol (increases flushing and hepatotoxicity risk)

Avoid if

  • Active liver disease
  • Severe gout
  • Unmonitored diabetes with high-dose nicotinic acid

Evidence

Study-level References

vitamin-b3-SRC-001Randomized controlled trial
Sourceopen_in_new

AIM-HIGH Investigators. *Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy.* NEJM. 2011;365(24):2255-2267.

Population: Statin-treated patients with established cardiovascular disease and low HDL-C

Dose protocol: Extended-release niacin 1,500–2,000 mg/day vs placebo, added to simvastatin

Key findings: No incremental clinical benefit of niacin despite improved HDL-C and TG. Trial stopped early for futility.

Notes: Definitive negative trial for niacin + statin CV combination.

Paper content

No incremental clinical benefit of niacin despite improved HDL-C and TG; trial stopped early for futility.

vitamin-b3-SRC-002Randomized controlled trial
Sourceopen_in_new

Chen AC, et al. *A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention.* NEJM. 2015;373(17):1618-1626. (ONTRAC)

Population: High-risk adults (≥2 non-melanoma skin cancers in prior 5 years)

Dose protocol: Nicotinamide 500 mg BID for 12 months

Key findings: 23% relative reduction in new non-melanoma skin cancers. Effect ceased after discontinuation.

Notes: Landmark trial for niacinamide skin chemoprevention.

Paper content

23% relative reduction in new non-melanoma skin cancers; effect ceased after discontinuation.

vitamin-b3-SRC-003Analysis / Trial context
Sourceopen_in_new

Boden WE, et al. *Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy.* (AIM-HIGH extended analysis / HPS2-THRIVE context). 2011.

Population: Statin-treated cardiovascular disease patients

Dose protocol: Extended-release niacin added to statin therapy

Key findings: Confirms no CV event benefit from niacin + statin. HPS2-THRIVE also showed no benefit with increased adverse events.

Notes: Together, AIM-HIGH and HPS2-THRIVE ended the era of routine niacin-statin combination therapy.

Paper content

Confirms no CV event benefit from niacin + statin; HPS2-THRIVE also showed no benefit with increased adverse events.

vitamin-b3-SRC-004Randomized, single-blind comparative trial.
Sourceopen_in_new

Rocio J, Kovylkina N, Cestari T, et al. A novel dermocosmetic routine containing vitamin B3 and 2-mercaptonicotinyl glycine significantly improves melasma after 3 months of daily use. J Cosmet Dermatol. 2025. doi:10.1111/jocd.70476. PMID:41036635.

Population: Women with melasma, mean age 44 years.

Dose protocol: Topical vitamin B3 (niacinamide) dermocosmetic serum applied daily for 6 months

Key findings: Niacinamide-based serum showed comparable melasma improvement to Kligman triple formula with superior tolerability in 91 women.

Notes: Supports topical niacinamide for skin pigmentation. Combination formulation limits attribution to niacinamide alone.

Paper content

This randomized single-blind trial compared a topical vitamin B3 (niacinamide) dermocosmetic serum against the established Kligman triple formula in 91 women with melasma over 6 months. Both treatments significantly improved MASI scores by 3 months, with comparable outcomes at 6 months. The niacinamide-based formulation showed superior tolerability. Quality of life and skin hydration improved in both groups. This study supports niacinamide as a tolerable topical option for melasma management, though the combination formulation makes it difficult to isolate the specific contribution of niacinamide alone.

vitamin-b3-SRC-005Phase 2 randomized controlled trial.
Sourceopen_in_new

Thomas S, Ben-Davies R, Cetinkaya-Fisgin A, et al. Evaluation of nicotinamide riboside in prevention of small nerve fiber axon degeneration and promotion of nerve regeneration. J Peripher Nerv Syst. 2026. doi:10.1111/jns.70101. PMID:41502156.

Population: Healthy adult volunteers in a capsaicin-induced nerve fiber degeneration model.

Dose protocol: Oral nicotinamide riboside versus placebo in a capsaicin-induced nerve degeneration model

Key findings: NR modestly increased skin NAD+ levels but did not prevent nerve fiber degeneration or promote regeneration. Negative finding for neuroprotection.

Notes: Important negative result that tempers enthusiasm for NAD+ precursors as neuroprotective agents at standard doses.

Paper content

This Phase 2 randomized trial tested whether oral nicotinamide riboside (NR), a NAD+ precursor form of vitamin B3, could prevent small nerve fiber degeneration or enhance nerve regeneration using a validated capsaicin-induced model in healthy volunteers. Despite modest increases in skin NAD+ levels, NR failed to prevent nerve fiber degeneration or improve regeneration compared to placebo. The authors concluded that oral NR at the doses used cannot be recommended for neuropathy prevention or nerve regeneration. This is an important negative finding that tempers enthusiasm for NAD+ precursors as neuroprotective agents, at least at standard supplemental doses.

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