Vitamin B3 (Niacin/Niacinamide)

Vitamin B3, known as niacin (nicotinic acid) or its amide form niacinamide (nicotinamide), is a water-soluble vitamin that serves as a precursor for the essential coenzymes NAD⁺ and NADP⁺. These coenzymes are central to cellular energy metabolism, DNA repair, and signaling pathways, making vitamin B3 indispensable for normal cellular function and systemic health.

• Cardiovascular health: Niacin at therapeutic doses (≥1 g/day) lowers LDL-cholesterol, raises HDL-cholesterol, and reduces triglycerides, a benefit documented in the Coronary Drug Project and subsequent meta-analyses.
• Metabolic support: NAD⁺ precursors improve mitochondrial function and insulin sensitivity; clinical trials show modest reductions in fasting glucose and HOMA-IR scores with nicotinamide riboside supplementation.
• Neuroprotection: NAD⁺ repletion protects neurons against oxidative stress; human trials indicate modest cognitive benefits in mild cognitive impairment when combined with lifestyle interventions.
• Dermatology: Topical niacinamide improves barrier function, reduces erythema, and decreases hyperpigmentation; randomized controlled trials show significant improvement in acne and rosacea.
• DNA repair & aging: Elevated NAD⁺ levels activate sirtuins and PARP enzymes, supporting genome stability; animal studies translate to human data showing decreased DNA damage biomarkers with supplementation.

• Conversion: Niacin is converted intracellularly to nicotinamide, then to nicotinamide adenine dinucleotide (NAD⁺) and its phosphorylated form NADP⁺.
• Coenzyme Function: These coenzymes act as electron carriers in glycolysis, the TCA cycle, and oxidative phosphorylation, enabling ATP production.
• Regulatory Roles: NAD⁺ also serves as a substrate for sirtuins (e.g., SIRT1), poly-ADP-ribose polymerases (PARPs), and CD38, regulating gene expression, DNA repair, and calcium signaling.
• Vasodilation: Niacin’s vasodilatory effect comes from the G-protein-coupled receptor GPR109A (HCA2) activation on endothelial cells, causing prostaglandin-mediated vasodilation and flushing.
• Flushing Avoidance: Niacinamide lacks GPR109A activity, thus avoids flushing while still providing NAD⁺.
• Cellular Effects: The increased NAD⁺ pool enhances mitochondrial biogenesis, reduces oxidative stress, and modulates inflammatory pathways (NF-κB inhibition).

• Niacin (nicotinic acid): C₆H₅NO₂ (molecular weight 123.11 g/mol). IUPAC name: 3-pyridinecarboxylic acid.
• Niacinamide (nicotinamide): C₆H₆N₂O (molecular weight 122.12 g/mol). IUPAC name: 3-pyridinecarboxamide.
• Structural Features: Both are aromatic heterocycles containing a pyridine ring with a carboxyl (acid) or amide (amide) functional group at the 3-position.
• Solubility: They are highly water-soluble (≈1 g/100 mL at 25 °C) with pKa values of ~4.8 (acid) and ~3.5 (amide).
• Chemical Properties: Niacin is a weak acid; niacinamide is neutral but can act as a hydrogen-bond donor/acceptor, facilitating enzyme binding.
• Stability: Their stability is pH-dependent: niacin is stable at acidic pH, while niacinamide is more stable at neutral to slightly alkaline pH, influencing formulation choices.

• Natural sources: Meat (especially liver), fish, poultry, legumes, and fortified cereals provide 10–30 mg/serving.
• Extraction: Industrially, niacin is produced via oxidation of 3-methylpyridine (3-picoline) using nitric acid or via catalytic oxidation of 3-pyridinecarboxylic acid. Niacinamide is obtained by reacting niacin with ammonia under high temperature and pressure (amide formation).
• Synthetic vs. natural: Most supplement-grade vitamin B3 is synthetically derived; purity ≥99 % is required for pharmaceutical grade.
• Quality considerations: Look for USP-verified or GMP-certified products, with certificates of analysis confirming absence of heavy metals, residual solvents, and confirming correct polymorphic form (β-nicotinic acid vs. α). Stability testing (e.g., accelerated shelf-life) ensures potency over the product’s shelf-life.