Niacin B3

Definition: Niacin or vitamin B3 is a water-soluble vitamin used by the body to form the nicotinamide coenzyme, NAD+. The term ‘niacin’ is often used to refer to nicotinic acid (pyridine-3-carboxylic acid) only, although other vitamers with a pyridine ring, including nicotinamide (pyridine-3-carboxamide) and nicotinamide riboside, also contribute to NAD+ formation. None of the vitamers are related to the nicotine found in tobacco, although their names are similar. Likewise, nicotine — but not nicotinic acid — is an agonist of the nicotinic receptors that respond to the neurotransmitter, acetylcholine.

  • The classical symptoms of severe vitamin B3 deficiency (pellagra) are dementia, dermatitis, and diarrhea. Some patients with pellagra present with only 1 or 2 of these symptoms. Other manifestations may include atrophic changes of the tongue, photosensitivity, and nutrient malabsorption. Early signs of vitamin B3 deficiency may include nervousness, headaches, forgetfulness, apprehension, and functional gastrointestinal disturbances, and may be mistaken for neurosis.
  • Causes of niacin deficiency include inadequate oral intake, poor bioavailability from unlimed grains, defective tryptophan absorption, metabolic disorders, and the long-term use of chemotherapeutic treatments.
  • NAD is the sole substrate for PARP enzymes and sirtuins involved in DNA repair activities; thus, NAD is critical for genome stability. Several studies, mostly using in vitro and animal models, suggest a possible role for niacin in cancer prevention. In a recent phase III trial, a daily pharmacologic dose of nicotinamide was found to reduce the rate of premalignant skin lesions and nonmelanoma cancers in high-risk subjects.
  • Despite promising initial results, nicotinamide administration has failed to prevent or delay the onset of type 1 diabetes mellitus in high-risk relatives of type 1 diabetic patients. Future research might explore the use of nicotinamide in combined therapy and evaluate activators of NAD-dependent enzymes.
  • At pharmacologic doses, nicotinic acid improved lipid profiles of patients with a history of vascular disease yet failed to reduce recurrent cardiovascular events or mortality.

Adverse effects

  • In patients being treated with niacin for hypercholesterolemia, side effects occur frequently and result in discontinuation of therapy in nearly 50% of cases.
  • The most common side effects are skin flushing, itching, and urticaria; these symptoms often improve rapidly despite the continuation of treatment. Niacin has been reported to increase blood glucose levels in some diabetic patients.
  • Other adverse effects of niacin may include hyperuricemia, gastrointestinal distress, reactivation of a pre-existing peptic ulcer, worsening of unstable angina (but no effect on stable angina), macular edema or cystoid maculopathy, myopathy, skin lesions resembling acanthosis nigricans, and blocking of the disulfiram (Antabuse) reaction.
  • Some side effects of niacin can be minimized by starting with low doses (such as 100 mg twice a day) and increasing gradually as tolerated. Gastrointestinal side effects, including activation of a peptic ulcer, may be preventable by using buffered niacin.
  • Hepatotoxicity is the most clinically important adverse effect of niacin, although it is uncommon in patients taking 3 g/day or less.

Drug interactions

  • Pellagra (skin lesions, diarrhea, and disturbances in affect) has been reported as a side effect of long-term anticonvulsant therapy. However, niacinamide in doses of 41–178 mg/kg of body weight per day has also been reported to inhibit the metabolism of primidone and carbamazepine in humans, which could potentially increase the toxicity of these drugs.
  • Administration of 80 or 500 mg of aspirin along with 500 mg of niacin decreased the incidence of niacin-induced warmth and skin flushing but did not prevent niacin-induced itching and tingling. The higher dose of aspirin was more effective than the lower dose. The clinical importance of this finding is unclear.
  • Isoniazid has been reported to cause pellagra in malnourished individuals, which was reversible by supplementation with niacin or niacinamide. Isoniazid presumably interferes with vitamin B3 absorption or metabolism because of its structural similarity to niacinamide.

Nutrient interactions

  • L-Tryptophan. According to one group of investigators, supplementation with niacinamide increases the efficacy of L-tryptophan by inhibiting the enzyme, tryptophan pyrrolase, which breaks down tryptophan in the liver. In the treatment of depression or insomnia, the combination of L-tryptophan and niacinamide may be more effective than either of these nutrients alone.

Food sources

  • Good food sources include meat, chicken, fish, whole grains, legumes, and dairy products.


  • While either niacin or niacinamide can prevent or reverse vitamin B3 deficiency, the therapeutic effects and side effects of these compounds differ substantially. Niacin influences serum lipid levels, but niacinamide does not. Niacin (but not niacinamide) is a component of the glucose tolerance factor and as such, when administered in relatively low doses along with chromium, may improve glucose tolerance. Niacinamide appears to be more effective than niacin in preventing the progression of type 1 diabetes because it is more efficiently taken up by pancreatic islets.
  • With respect to niacin preparations, time-release niacin may be less likely than regular niacin to cause skin flushing, but its greater hepatotoxicity is cause for concern. A newer “extended-release” niacin formulation (Niaspan) is said to cause less flushing than regular niacin and less hepatotoxicity than sustained-release niacin.
  • I typically use niacinamide (because of its lower toxicity profile) for most vitamin B3-responsive conditions. Niacin is used to treat lipid disorders and may be given in low doses (such as 100 mg/day) as a precursor to glucose tolerance factor. In addition, niacin may be tried for vitamin B3-responsive psychiatric disorders that do not improve with niacinamide. Niacinamide from various suppliers contains up to 4% of different impurities, including niacin. The presence of a small amount of niacin may explain the occasional reports from patients that niacinamide causes their skin to flush. Crystallization of niacinamide reduces the impurities to undetectable levels.

Dosage and administration

  • The most frequently used dosages of vitamin B3 are 500–3,000 mg/day. Because of their relatively short half-life, immediate-release niacin and niacinamide preparations should be taken in at least 3 divided doses per day.

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