Approach
Patients with gastrointestinal, dermatological, and/or neurological clinical features of pellagra, as well as those with marginal deficiency, should be treated with niacin in combination with riboflavin and pyridoxine.
Marginal deficiency is suggested by a dietary history indicating that food sources rich in niacin (vitamin B3), riboflavin (vitamin B2), and pyridoxine (vitamin B6) are not frequently eaten. Dietary deficiency may result from the consumption of a corn-based, low-protein diet, or from a vegan diet (no animal products) with few niacin and/or tryptophan sources; or it may occur in very poor, homeless, or displaced people; those with an eating disorder (e.g., anorexia nervosa, bulimia nervosa); and those with chronic alcohol use disorder. General advice on sound dietary practices and good sources of niacin and other B vitamins should be given to all patients.
Treatment of pellagra
Diagnosis of vitamin B3 deficiency in symptomatic patients can be confirmed with a therapeutic trial of niacin, in the form of nicotinamide (niacinamide). In the presence of vitamin B3 deficiency, improvement in cutaneous symptoms and many neurological symptoms usually occurs within 48 hours of treatment.[8] If there is clinical improvement, therapy should be continued for 3 to 4 weeks at a dose appropriate to the severity of the presenting clinical features.[2][9][19][43][50][65][90][91][92]
Nicotinic acid (niacin) replacement therapy should be administered in a multivitamin supplement preparation to ensure that other related vitamins, such as riboflavin (vitamin B2) and pyridoxine (vitamin B6), are also provided.[43][82]
Nicotinamide (niacinamide) is preferred, as large doses of niacin cause nausea and vomiting, and flushing of the skin, as well as numbness and tingling of the tongue and lower jaw.[9][46] Although a timed-release preparation of niacin is available, it is not a recommended treatment due to its associated higher risks of side effects. Generally, the incidences of hepatic and gastrointestinal side effects have been significantly greater with use of timed-release niacin when compared to an immediate-release form.
Adverse effects have been reported in patients taking large pharmacological doses of nicotinic acid (niacin), although preparations with 100 mg of nicotinic acid (niacin) are generally considered safe.[43] Doses above 350 mg/day can lead to nausea, flushing, and diarrhoea. Jaundice has been reported at doses as low as 750 mg/day. Doses above 2500 mg/day have been associated with glucose intolerance and hyperglycaemia, heartburn, increased serum uric acid, flushing, hepatotoxicity, a sore throat, fatigue, hives, and inability to focus the eyes. Patients with documented nicotinic acid (niacin) sensitivity should be treated with time-release formulations, although reduction in the frequency and severity of adverse effects with these preparations has not been well documented.
Treatment of marginal deficiency
The development of pellagra in at-risk, asymptomatic patients of all ages can be prevented with low-dose nicotinic acid (niacin) replacement therapy in the form of nicotinamide (niacinamide).[9] Nicotinamide (niacinamide) is preferred, as large doses of nicotinic acid (niacin) cause nausea and vomiting, and flushing of the skin, as well as numbness and tingling of the tongue and lower jaw.[9][46]
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