Vitamin B3


Article Author:
Basil Peechakara


Article Editor:
Mohit Gupta


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Phillip Hynes
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Sandeep Sekhon


Updated:
9/30/2019 9:32:37 PM

Indications

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. Deficiency of the vitamin, also known as pellagra
  2. Dyslipidemia

Indication for Pellagra

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

Indication for Dyslipidemia

Therapeutic doses of niacin can reduce the level of total cholesterol 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] Its use is 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

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, and amino acid metabolism, pentose biosynthesis, glycerol metabolism, synthesis of high energy phosphate bonds, and fatty acid metabolism.[3] As cellular functions in many organs and tissues are affected by the deficiency of niacin, the clinical expression of pellagra is diverse.

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, which is 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.[2]

Administration

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

Dosing

Pellagra

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.[3] 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.

Dyslipidemia

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 effect 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

Flushing

Niacin causes vasodilation of small subcutaneous blood vessels mediated by prostaglandin D2 that leads to a cutaneous flush, 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, aspirin or ibuprofen is helpful.

Peptic Ulcer Disease

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

Hepatotoxicity

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.

Hyperglycemia

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

Arrhythmia

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.[7]

Pellagra

Vitamin B3 underdosing in vulnerable population groups may result in pellagra, which is characterized by 4 Ds in clinical manifestations: diarrhea, dermatitis, dementia, and death.

Dermatitis: The diagnosis is challenging in the absence of the 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.[8] 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.

Diarrhea: Gastrointestinal disturbances include diarrhea, nausea, vomiting, epigastric discomfort, poor appetite, abdominal pain, and increased salivation. Stools are typically watery but can be bloody or mucoid occasionally.

Neurologic manifestation: Presents as nonspecific symptoms like confusion, hallucinations, irritability, psychomotor unrest, ataxia, and depression. As the disease advances, patients become confused, disoriented, and delirious, then comatose and stuporous, and finally die.

Contraindications

Contraindications to the use of niacin are as follows:

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

Monitoring

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.[9]

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]

Toxicity

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

Enhancing Healthcare Team Outcomes

Healthcare workers, including nurse practitioners and the primary care provider, should not empirically encourage patients to take niacin. It is only recommended if there is a deficiency. For the management of hyperlipidemia, 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 veggies to obtain their niacin. Reliance on supplements is not recommended because of fake and counterfeit products.[10]

When using niacin, an interprofessional approach is useful, especially depending on why it is necessary. The clinician will initiate therapy; if for pellagra or deficiency, a nurse, pharmacist, and dietician should all work together to resolve the condition. For dyslipidemia, a cardiologist may also be necessary. Pharmacists will verify the dosing based on the condition and can offer counsel to the patients, as can the nurse. For example, it is sometimes recommended to take a baby aspirin before dosing niacin to help prevent the flushing. Of course, this would be with once-daily dosing. The nurse should counsel the patient on what to expect with niacin therapy, and monitor for adverse effects as well as patient compliance and treatment effectiveness. The dietician can review the patient's eating habits to determine where the possible deficiency lies. All these ancillary providers need to keep the treating clinician informed at all times. Thus, with an interprofessional collaborative approach, niacin therapy can deliver optimal therapeutic results with minimal adverse effects to the patient. [Level V]


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Vitamin B3 - Questions

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A patient with pellagra is evaluated in the clinic and prescribed the appropriate therapy. The patient asks what food would help him maintain adequate levels of niacin. What would be an appropriate response?



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A 50-year-old male comes to the clinic with broad hyperpigmented patches around his neck. He is found to have the deficiency of a vitamin. Which is one of the clinical manifestations resulting from its deficiency?



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A 68-year-old patient with a past history of hyperlipidemia controlled on atorvastatin comes to the clinic for a routine checkup. He feels well and has no complaints currently. His blood pressure is 118/70 mm Hg, pulse rate is 88 bpm, respiratory rate is 13 cycles per minute and BMI is 32 kg/m2. The physical exam is unremarkable. After review of his lab reports, he is found to have an HDL level of 30 g/dl. He is advised to take niacin. The patient asks if he should be concerned about a possible side effect of the medication. Which of the following symptoms should prompt caution with its use in the patient?



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A 65-year-old man with a past medical history of diabetes and hypertension for the last seven years is found to have a low HDL level on lab results after a routine clinic visit for preventive measure. The clinician starts him on niacin therapy. What lab test must be routinely done to monitor the development of a common adverse effect due to the medication?



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A 65-year-old man comes to the clinic for a routine check-up. He has a history of hypertension and hyperlipidemia for which he is on losartan and atorvastatin. He has no complaints presently. Family history is insignificant. He has a sedentary lifestyle and eats fast food mostly. There is no history of alcohol or tobacco use. On examination, he is in no distress and has a BMI of 35. Lab reports are as follows: fasting glucose: 98 mg/dl; Total cholesterol 190 mg/dl; LDL: 142 mg/dl; HDL: 20 mg/dl;TSH: 4 microU/mL; serum creatinine: 0.7mg/dl. Apart from lifestyle modifications, which drug can be added for optimal therapy?



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Vitamin B3 - References

References

Isaac S, The     [PubMed]
Park YK,Sempos CT,Barton CN,Vanderveen JE,Yetley EA, Effectiveness of food fortification in the United States: the case of pellagra. American journal of public health. 2000 May     [PubMed]
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. Journal of lipid research. 1980 Nov     [PubMed]
Hegyi J,Schwartz RA,Hegyi V, Pellagra: dermatitis, dementia, and diarrhea. International journal of dermatology. 2004 Jan     [PubMed]
Kashyap ML, Mechanistic studies of high-density lipoproteins. The American journal of cardiology. 1998 Dec 17     [PubMed]
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. The American journal of cardiology. 2002 Mar 15     [PubMed]
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 2     [PubMed]
Schwartz ML, Severe reversible hyperglycemia as a consequence of niacin therapy. Archives of internal medicine. 1993 Sep 13     [PubMed]
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? Medical science monitor : international medical journal of experimental and clinical research. 2015 Jul 25     [PubMed]
Barry J, Fake medicines: a global threat. Nursing management (Harrow, London, England : 1994). 2014 Nov 27;     [PubMed]

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