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Vitamin B3

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Last Update: June 11, 2022.

Continuing Education Activity

Niacin is a medication used in the management and treatment of pellagra and hyperlipidemia. It is part of the B complex vitamins. This activity outlines the indications, action, and contraindications for niacin as a valuable agent in the treatment of pellagra and hyperlipidemia.


  • Outline the indications for niacin.
  • Explain the mechanism of action of niacin.
  • Describe the adverse effects of niacin.
  • Summarize interprofessional team approach to enhance communication and patient care to improve niacin therapy and optimize patient outcomes.
Access free multiple choice questions on this topic.


Niacin, known as vitamin B3, is a water-soluble vitamin of the B complex group of vitamins. Food such as bran, yeast, eggs, peanuts, poultry, red meat, fish, whole-grain cereals, legumes, and seeds are rich sources of the vitamin. As a drug, it has two main indications.

  1. Dyslipidemia(FDA approved use)(types IIa and IIb or primary hypercholesterolemia)
  2. Deficiency of the vitamin, also known as pellagra

Indication for Dyslipidemia

Therapeutic doses of niacin can reduce total cholesterol levels up to 25%, low-density lipoprotein (LDL) up to 10% to 15%, and triglycerides by up to 20% to 50%. Niacin has the highest efficacy to raise high-density cholesterol (HDL), with an increase of 15% to 35%.[1] Niacin is used in moderate to high doses (1000 to 3000 mg per day) for refractory dyslipidemia and cases warranting HDL increase.

With more evaluation, niacin may be in a grouping with hypolipidemic drugs used for patients with[2]

  • Concomitant hypercholesterolemia and statin intolerance
  • Metabolic syndrome
  • Patients unresponsive to hypolipidemic therapy of targeted LDL cholesterol values

Indication for Pellagra

Pellagra is a deficiency of vitamin B3. Niacin is indicated in the treatment of pellagra until the symptoms resolve, most commonly for the relief of skin symptoms.

Mechanism of Action

Niacin is necessary for adequate cellular metabolism and function as a vital component in coenzyme 1 (the oxidized form of nicotinamide adenine dinucleotide [NAD]) and coenzyme 2 (the reduced form of nicotinamide adenine dinucleotide phosphate [NADP]), which either accept or donate hydrogen ions in essential oxidation-reduction reactions. They are important coenzymes for glycolysis, pyruvate metabolism, protein, amino acid metabolism, pentose biosynthesis, glycerol metabolism, synthesis of high energy phosphate bonds, and fatty acid metabolism.[2]

As cellular functions in many organs and tissues are affected by the deficiency of niacin, the clinical expression of pellagra is diverse. Niacin underdosing in vulnerable population groups may result in pellagra, which is characterized by 4 Ds in clinical manifestations, diarrhea, dermatitis, dementia, and death. The diagnosis of dermatitis is challenging in the absence of skin lesions and is more straightforward if characteristic skin lesions are present. Dermatitis begins as erythema, resembles sunburn in the initial stages, but tanning occurs more slowly than typically seen in sunburn. The lesion is a bilaterally symmetrical eruption located at sites of sunlight exposure.[3] 

Cutaneous patches on the neck are known as Casal necklace. It extends as a broad collar around the cervical dermatomes C3 and C4 in the neck. Gastrointestinal disturbances include diarrhea, nausea, vomiting, epigastric discomfort, poor appetite, abdominal pain, and increased salivation. Neurologic manifestation presents as nonspecific symptoms like confusion, hallucinations, irritability, psychomotor unrest, ataxia, and depression. As the disease advances, patients become confused, disoriented, delirious, comatose, and stuporous, and finally die.

Mechanism of action of niacin in dyslipidemia includes inhibition of lipolysis within adipose tissue, reduction in liver triacylglycerol formation, increase in lipoprotein lipase activity, inhibition of synthesis of apo B-100 and hepatic very-low-density lipoprotein (VLDL), impaired cholesterol biosynthesis, and lowering of the fractional catabolic rate of HDL-Apo A-1. Apo A-1, an activator of lecithin cholesterol acyltransferase (LCAT), has a significant role in reverse cholesterol transport.[4] Niacin decreases the risk of cardiovascular disease by exhibiting a plethora of pleiotropic effects, especially by its anti-oxidative and anti-inflammatory actions and by increasing serum adiponectin.[5]


Recommended daily allowance of niacin is as follows:[5]

  • Infants: 5 to 6 mg
  • Children: 9 to 13 mg
  • Adults: 13 to 20 mg
  • Pregnant and lactating mothers: 17 mg and 20 mg, respectively



The adult dose is nicotinamide 100 mg orally, every 6 hours for several days until relief of acute symptoms, followed by 50 mg every 8 to 12 hours until all skin lesions heal. In severe cases (marked neurological or gastrointestinal tract symptoms), 1 g three to four times a day can be given, initially by the parenteral route. For children, one can use 10 to 50 mg orally every 6 hours until symptoms of pellagra resolve. For mild endemic pellagra, smaller doses such as 10 mg per day are acceptable. Therapy should include other B vitamins, magnesium, and zinc, as well as a calorie-rich diet. Topical emollients may reduce discomfort due to skin lesions.[2] Sustained-release (SR) formulations have been developed, which are available over-the-counter. Sustained-release niacin can be administered once daily and is less likely to cause flushing. However, it does not have approval for use in hyperlipidemia, and some studies showed a high likelihood of hepatotoxicity.


The recommended dose for hyperlipidemia is 1 to 6 g daily, initially low doses (100 mg three times per day), increasing at weekly intervals depending upon clinical efficacy and tolerance. Extended-release (ER) niacin in concentrations from 125 to 1000 mg is approved for use in hyperlipidemia and does not have hepatotoxicity compared to regular niacin.[6]

Adverse Effects


Niacin causes vasodilation of small subcutaneous blood vessels mediated by prostaglandin D2, leading to cutaneous flushing, accompanied by an uneasy sensation of pruritus and warmth. Severe flushing may lead to hypotension and dizziness. Flushing appears earlier after dosing with immediate-release (IR) niacin (approximately 30 minutes) and delayed for sustained-release niacin (2 to 4 hours). Patients should avoid hot showers immediately after a dose, and if necessary, pretreatment with aspirin or ibuprofen is helpful. Laropiprant is a selective prostaglandin D2 receptor 1 antagonist that can decrease niacin-induced flushing.[7]

Peptic Ulcer Disease

Niacin therapy may aggravate peptic ulcer disease. Therefore, niacin should be used cautiously with active or chronic gastrointestinal disorders.


The most serious adverse effect is niacin hepatotoxicity. A mild increase in hepatic transaminase levels up to twice the upper limit of the normal range is common.


Decreased glucose tolerance and hyperglycemia can occur in individuals with diabetes and appears to result from insulin resistance consequent to the free fatty acid rebound after moderately-sized doses.


Patients with supraventricular tachycardias (SVTs) may experience unusual chest sensations and palpitations even when the SVTs are under control via concomitant antiarrhythmic therapy.

Eye Symptoms

Reports also exist of retinal edema or toxic amblyopia, resulting in blurred vision.[8]


Niacin is known to cause hyperuricemia. Therefore, niacin is avoided in patients with a history of gout.[9]


  • Peptic ulcer disease
  • Active hepatic disease or elevation in transaminases
  • Hypersensitivity reactions   


Niacin Therapy for Pellagra

  • A combined excretion of pyridone and N-methyl nicotinamide of less than 1.5 mg in 24 hours points toward severe niacin deficiency.

Niacin therapy for Dyslipidemia

  • Recommendations include monitoring of uric acid, blood glucose, and potassium.[10]

Maximum Tolerated Dose of Niacin

  • Immediate-release formulation: 6 g/day in 2 to 3 divided doses,
  • Sustained-release formulation: 2000 mg per day.[6]


Symptoms of toxicity include nausea, vomiting, diarrhea, flushing, dizziness, and palpitations. Treatment of toxicity involves supportive care, including gastric lavage.[11]

Enhancing Healthcare Team Outcomes

Healthcare workers, including nurse practitioners and clinicians, should not empirically encourage patients to take niacin. It is only recommended if there is a deficiency. For hyperlipidemia management, the vitamin often causes intolerable side effects, and its use is declining. The majority of the public should be encouraged to eat fresh fruit and vegetable to obtain their niacin. Reliance on supplements is not recommended because of fake and counterfeit products.[12]

The clinician initiates the therapy with niacin for pellagra or dyslipidemia. Here, excellent communication between clinician, nurse, pharmacist, and dietician is necessary. For dyslipidemia leading to coronary artery disease, a referral to a cardiologist may be necessary. Pharmacists will verify the dosing based on the condition and counsel the patients regarding the adverse drug reactions. For example, It is sometimes recommended to take a baby aspirin before dosing niacin to help prevent flushing. The nurse should counsel the patient on what to expect with niacin therapy and monitor compliance and treatment effectiveness. The clinical dietician can design a patient-centered diet plan to improve dyslipidemia and pellagra. Thus, with an interprofessional collaborative team approach, niacin therapy can deliver optimal therapeutic results with minimal adverse effects to the patient. [Level 5]

Review Questions


Pownall HJ, Jackson RL, Roth RI, Gotto AM, Patsch JR, Kummerow FA. Influence of an atherogenic diet on the structure of swine low density lipoproteins. J Lipid Res. 1980 Nov;21(8):1108-15. [PubMed: 7462806]
Hegyi J, Schwartz RA, Hegyi V. Pellagra: dermatitis, dementia, and diarrhea. Int J Dermatol. 2004 Jan;43(1):1-5. [PubMed: 14693013]
Isaac S. The "gauntlet" of pellagra. Int J Dermatol. 1998 Aug;37(8):599. [PubMed: 9732006]
Kashyap ML. Mechanistic studies of high-density lipoproteins. Am J Cardiol. 1998 Dec 17;82(12A):42U-48U; discussion 85U-86U. [PubMed: 9915662]
Zeman M, Vecka M, Perlík F, Hromádka R, Staňková B, Tvrzická E, Žák A. Niacin in the Treatment of Hyperlipidemias in Light of New Clinical Trials: Has Niacin Lost its Place? Med Sci Monit. 2015 Jul 25;21:2156-62. [PMC free article: PMC4523006] [PubMed: 26210594]
Kashyap ML, McGovern ME, Berra K, Guyton JR, Kwiterovich PO, Harper WL, Toth PD, Favrot LK, Kerzner B, Nash SD, Bays HE, Simmons PD. Long-term safety and efficacy of a once-daily niacin/lovastatin formulation for patients with dyslipidemia. Am J Cardiol. 2002 Mar 15;89(6):672-8. [PubMed: 11897208]
Maccubbin D, Koren MJ, Davidson M, Gavish D, Pasternak RC, Macdonell G, Mallick M, Sisk CM, Paolini JF, Mitchel Y. Flushing profile of extended-release niacin/laropiprant versus gradually titrated niacin extended-release in patients with dyslipidemia with and without ischemic cardiovascular disease. Am J Cardiol. 2009 Jul 01;104(1):74-81. [PubMed: 19576324]
McKenney JM, Proctor JD, Harris S, Chinchili VM. A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients. JAMA. 1994 Mar 02;271(9):672-7. [PubMed: 8309029]
Ben Salem C, Slim R, Fathallah N, Hmouda H. Drug-induced hyperuricaemia and gout. Rheumatology (Oxford). 2017 May 01;56(5):679-688. [PubMed: 27498351]
Schwartz ML. Severe reversible hyperglycemia as a consequence of niacin therapy. Arch Intern Med. 1993 Sep 13;153(17):2050-2. [PubMed: 8357290]
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. National Institute of Diabetes and Digestive and Kidney Diseases; Bethesda (MD): Jul 9, 2020. Niacin. [PMC free article: PMC547852] [PubMed: 31643504]
Barry J. Fake medicines: a global threat. Nurs Manag (Harrow). 2014 Nov 27;21(8):17. [PubMed: 25428316]
Nouh AH, Elshahid AR, Kadah AS, Zeyada YA. Topical niacinamide (Nicotinamide) treatment for discoid lupus erythematosus (DLE): A prospective pilot study. J Cosmet Dermatol. 2023 May;22(5):1647-1657. [PubMed: 36683259]
Van Bergen NJ, Walvekar AS, Patraskaki M, Sikora T, Linster CL, Christodoulou J. Clinical and biochemical distinctions for a metabolite repair disorder caused by NAXD or NAXE deficiency. J Inherit Metab Dis. 2022 Nov;45(6):1028-1038. [PMC free article: PMC9804276] [PubMed: 35866541]

Disclosure: Basil Peechakara declares no relevant financial relationships with ineligible companies.

Disclosure: Mohit Gupta declares no relevant financial relationships with ineligible companies.

Copyright © 2024, StatPearls Publishing LLC.

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Bookshelf ID: NBK526107PMID: 30252363


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