What drugs cause niacin deficiency?

October 8, 2025 •

3 min read

While dietary insufficiency is a known cause, several therapeutic drugs can also provoke niacin deficiency, a condition that can lead to pellagra [1.3.1]. Understanding what drugs cause niacin deficiency is crucial for at-risk patients, including those on long-term treatments for tuberculosis or cancer.

Quick Summary

Certain medications can interfere with niacin absorption or metabolism, leading to a deficiency known as pellagra. Key drugs include isoniazid, pyrazinamide, fluorouracil, mercaptopurine, and some anticonvulsants.

Key Points

Causative Drugs: Several medications can cause niacin (vitamin B3) deficiency, a condition known as pellagra [1.3.1].
Isoniazid: The antituberculosis drug isoniazid is a primary cause, as its structure mimics niacin and it interferes with niacin synthesis from tryptophan [1.5.1, 1.5.5].
Chemotherapy Agents: Anticancer drugs like 5-fluorouracil and 6-mercaptopurine can induce deficiency by disrupting metabolic pathways [1.6.1, 1.7.2].
Anticonvulsants: Medications such as phenobarbital and phenytoin have also been linked to drug-induced pellagra [1.2.2, 1.3.4].
Mechanism: These drugs typically work by either inhibiting niacin absorption, acting as a competitive inhibitor, or disrupting the conversion of tryptophan to niacin [1.3.2, 1.5.1].
Pellagra Symptoms: The classic signs of deficiency are the "4 Ds": dermatitis (especially in sun-exposed areas), diarrhea, dementia, and potentially death if untreated [1.9.4].
Treatment: Management involves niacin or nicotinamide supplementation, which typically leads to rapid improvement of symptoms [1.9.4].

The Critical Role of Niacin (Vitamin B3) in the Body

Niacin, also known as vitamin B3, is a water-soluble vitamin essential for hundreds of bodily functions. It is a precursor to the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are vital for cellular metabolism, energy production, and DNA repair [1.5.4, 1.9.5]. The body can obtain niacin through diet from sources like meat, fish, poultry, and fortified grains, or it can synthesize it from the amino acid tryptophan [1.7.1]. A deficiency in niacin leads to a systemic disease called pellagra, classically characterized by the "4 Ds": dermatitis, diarrhea, dementia, and, if left untreated, death [1.9.2, 1.9.4]. While primary pellagra from poor diet is now rare in developed nations, secondary pellagra caused by conditions or medications that interfere with niacin absorption or metabolism persists [1.2.2, 1.2.4].

Primary Medications Implicated in Niacin Deficiency

A number of pharmacological agents have been identified as causes of secondary pellagra by disrupting the body's ability to use or synthesize niacin. This interference can occur through several mechanisms, including competitive inhibition, blocking absorption, or disrupting metabolic pathways [1.3.2, 1.5.1].

Antitubercular Drugs

Isoniazid (INH) is one of the most well-documented drugs to cause niacin deficiency [1.2.3, 1.2.4]. Its structural similarity to niacin allows it to act as a competitive inhibitor [1.3.2]. Isoniazid interferes with the conversion of tryptophan to niacin by binding with vitamin B6 (pyridoxine), an essential cofactor for the enzyme kynureninase in this pathway [1.5.1, 1.5.4]. It may also inhibit the intestinal absorption of niacin directly [1.2.1, 1.5.1]. Pyrazinamide, another antituberculosis drug, also has a structure similar to niacin and can contribute to deficiency [1.2.1, 1.3.2].

Chemotherapeutic Agents

Several drugs used in cancer treatment can induce pellagra by disrupting metabolic processes.

5-Fluorouracil (5-FU): This anticancer agent can lead to niacin deficiency and exacerbate symptoms in patients with low niacin status [1.6.1, 1.6.2]. The mechanism involves the inhibition of the conversion of tryptophan to niacin [1.3.5].
6-Mercaptopurine (6-MP): An immunosuppressant and chemotherapy drug, 6-mercaptopurine is also known to cause pellagra-like dermatitis [1.3.1, 1.7.2]. It is believed to inhibit NAD phosphorylase (Korenberg's enzyme), which interferes with niacin's metabolic function [1.3.5].
Azathioprine: This drug, which metabolizes into 6-mercaptopurine, also carries the risk of inducing pellagra [1.2.2, 1.7.4].

Anticonvulsants

Certain antiepileptic drugs (AEDs) have been linked to drug-induced pellagra, though the exact mechanisms are not always fully understood [1.3.5]. Phenobarbital and phenytoin are among the anticonvulsants cited as potential causes [1.2.2, 1.3.4]. It is hypothesized that they interfere with the tryptophan-niacin metabolic pathway [1.3.5]. Long-term use of these medications may warrant monitoring for signs of nutritional deficiencies.

Other Implicated Medications

Other drugs have also been associated with niacin deficiency, including:

Chloramphenicol: An antibiotic [1.3.1, 1.3.4].
Ethionamide: A second-line antituberculosis drug [1.3.2, 1.3.5].

Comparison of Drugs Causing Niacin Deficiency


Drug Class	Medication(s)	Primary Mechanism of Niacin Depletion
Antitubercular	Isoniazid, Pyrazinamide	Structural analogs of niacin; Isoniazid also depletes the B6 cofactor needed for niacin synthesis from tryptophan [1.2.1, 1.5.1, 1.5.5].
Chemotherapy	5-Fluorouracil	Inhibits the conversion of tryptophan to niacin [1.3.5].
Chemotherapy / Immunosuppressant	6-Mercaptopurine, Azathioprine	Inhibits NAD phosphorylase, interfering with niacin metabolism [1.3.5, 1.7.4].
Anticonvulsants	Phenobarbital, Phenytoin	Thought to interfere with the tryptophan-niacin pathway [1.2.2, 1.3.5].

Recognizing and Managing Drug-Induced Pellagra

Diagnosing drug-induced pellagra relies on recognizing the clinical symptoms in a patient taking an offending medication. The classic sign is a photosensitive dermatitis, often appearing as a symmetric rash on sun-exposed areas like the neck (Casal's necklace), hands, and face [1.9.2, 1.9.4]. Gastrointestinal issues like diarrhea, nausea, and loss of appetite are also common [1.9.1, 1.9.5]. Neurological symptoms can range from anxiety and confusion to dementia and delirium in severe cases [1.9.2].

Diagnosis is typically based on these clinical symptoms, as there are no definitive chemical tests, though low urinary levels of niacin metabolites can be indicative [1.9.5]. The treatment is straightforward: discontinuation of the causative drug if possible and supplementation with niacin or nicotinamide [1.3.3, 1.9.4]. Patients often show rapid improvement within days of starting supplementation [1.9.4]. A high-protein diet and supplementation with other B vitamins are also recommended for full recovery [1.3.6].

Conclusion

While niacin deficiency is uncommon in well-nourished populations, the risk of secondary, drug-induced pellagra is a significant clinical consideration for patients on specific long-term medications. Antitubercular drugs like isoniazid, chemotherapies such as 5-fluorouracil and 6-mercaptopurine, and certain anticonvulsants can all disrupt niacin metabolism and lead to deficiency. Clinicians should be vigilant for the signs of pellagra—dermatitis, diarrhea, and cognitive changes—in patients taking these drugs, particularly those with other risk factors like malnutrition or chronic alcoholism [1.2.4, 1.3.2]. Prompt diagnosis and niacin supplementation are key to reversing the condition and preventing severe complications.

For further reading, see the National Institutes of Health's Health Professional Fact Sheet on Niacin: https://ods.od.nih.gov/factsheets/Niacin-HealthProfessional/

Frequently Asked Questions

Isoniazid, a medication used to treat tuberculosis, is one of the most frequently cited drugs that causes niacin deficiency and pellagra [1.2.3, 1.3.2].

Isoniazid has a similar chemical structure to niacin and interferes with its use. It also binds with vitamin B6, which is a necessary cofactor for the body to produce its own niacin from the amino acid tryptophan [1.5.1, 1.5.4].

Yes, certain chemotherapeutic agents, including 5-fluorouracil, 6-mercaptopurine, and azathioprine, can interfere with niacin metabolism and cause a deficiency [1.3.1, 1.3.4, 1.7.4].

The classic symptoms are known as the '4 Ds': dermatitis (a rash on sun-exposed skin), diarrhea, and dementia (cognitive and neurological issues). If not treated, it can lead to death [1.9.2, 1.9.4].

Yes, some anticonvulsants like phenobarbital and phenytoin have been associated with causing pellagra, likely by interfering with the tryptophan-niacin metabolic pathway [1.2.2, 1.3.5].

Diagnosis is usually based on clinical symptoms in a patient taking a known causative drug. Treatment involves supplementing with niacin (vitamin B3) or nicotinamide and, if possible, stopping the offending medication [1.9.3, 1.9.4].

In the developed world, the most common cause of pellagra is chronic alcoholism, which leads to poor nutrition and malabsorption of niacin [1.2.4, 1.3.2].