Step by Step
NAD
Niacin forms NAD⁺ and NADP⁺
Niacin (nicotinic acid/nicotinamide) is the precursor for NAD⁺ (nicotinamide adenine dinucleotide) and NADP⁺ (nicotinamide adenine dinucleotide phosphate) — arguably the most important coenzymes in metabolism. NAD⁺: accepts electrons in catabolism (glycolysis, Krebs, beta-oxidation) → NADH → ETC → ATP. NADP⁺: used in anabolism and antioxidant defense → NADPH (from PPP).
Memory trick: Niacin = NAD⁺ = energy metabolism's backbone. Without it, nothing works.
Try
Synthesized from tryptophan — conditionally essential
Niacin can be synthesized from the amino acid tryptophan (60 mg tryptophan → 1 mg niacin). Requires B6, B2, and iron. This means niacin is conditionally essential — adequate protein intake can partially compensate for low dietary niacin. Hartnup disease (impaired tryptophan absorption) can cause pellagra even with adequate niacin intake.
Memory trick: Tryptophan → niacin. Turkey (tryptophan) can save you from pellagra.
Pel
Pellagra — the 4 Ds
Pellagra = niacin deficiency. Classic 4 Ds: Dermatitis (photosensitive rash — Casal's necklace on exposed areas), Diarrhea, Dementia (encephalopathy), Death (if untreated). Common in populations relying on corn (maize) as staple — corn is low in niacin AND tryptophan, and niacin in corn is bound (niacytin) and not bioavailable unless treated with lime (nixtamalization — Mesoamerican tradition that releases niacin).
Memory trick: Pellagra = 4 Ds: Dermatitis, Diarrhea, Dementia, Death.
Pharm
High-dose niacin — pharmacological use
High-dose niacin (1-3 g/day, well above RDA of 14-16 mg) is used as a lipid-lowering agent: raises HDL (most effective agent for this), lowers TGs, lowers LDL. Side effects: cutaneous flushing (prostaglandin-mediated, prevented by aspirin), hepatotoxicity (especially extended-release form), hyperglycemia, hyperuricemia. Less commonly used since statins became standard.
Applied Walkthrough
1
A corn-dependent rural population in 19th-century Southern US develops pellagra — corn provides calories but inadequate niacin (and bound niacytin), leading to endemic pellagra.
2
Classic presentation: farmer develops photosensitive rash on the neck (Casal's necklace), diarrhea, and progressive confusion — the 4 Ds.
3
Traditional Mexican tortillas made with lime-soaked corn (nixtamalization) do NOT cause pellagra — lime releases bound niacin. Populations that adopted corn without this technique developed pellagra.
4
A patient with Hartnup disease (impaired neutral amino acid absorption) cannot absorb tryptophan → cannot synthesize niacin → pellagra-like rash and neurological symptoms despite adequate dietary niacin.
Exam Application
Exams test niacin's coenzyme forms (NAD⁺ for catabolism, NADP⁺ for anabolism/antioxidant), pellagra's 4 Ds, the corn connection (low niacin + bound niacytin), tryptophan as an alternative source, Hartnup disease, and high-dose niacin's pharmacological effects (raises HDL, causes flushing). The NADH vs NADPH distinction carries over from earlier lessons.
⚠ Common Trap
Students forget that niacin can be made from tryptophan — this is why pure protein malnutrition (kwashiorkor) can cause pellagra-like symptoms, and why Hartnup disease causes pellagra. Also: the flushing from pharmacological niacin is mediated by prostaglandins (NOT histamine) and can be prevented by taking aspirin 30 minutes before — this distinction is tested.
✓ Quick Self-Check
1. What coenzymes does niacin (B3) form?
NAD⁺ (used in catabolic reactions — accepts electrons → NADH → ETC) and NADP⁺ (used in anabolic reactions — reduced to NADPH in the pentose phosphate pathway).
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2. What are the 4 Ds of pellagra?
Dermatitis (photosensitive), Diarrhea, Dementia, Death.
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3. Why does a corn-based diet cause pellagra?
Corn is low in both niacin and tryptophan, and its niacin is bound as niacytin (not bioavailable) unless treated with lime (nixtamalization).
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4. What amino acid can be converted to niacin?
Tryptophan — 60 mg tryptophan → 1 mg niacin (requires B6, B2, and iron).
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5. What is the mechanism of flushing from high-dose niacin?
Prostaglandin-mediated cutaneous vasodilation — prevented by taking aspirin 30 minutes before niacin.
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