Isoniazid, Pyrazinamide, Rifampin & Nutrient Depletion
Also searched as Rifater. What the clinical evidence reports, what it may mean, and what to discuss with your pharmacist.
Isoniazid, Pyrazinamide, Rifampin has been associated with depletion of NIACIN, NIACINAMIDE, VITAMIN B6 and VITAMIN D and 1 more. This does not mean a deficiency will occur — it means these are worth knowing about and, if you take Isoniazid, Pyrazinamide, Rifampin long-term, worth raising with your pharmacist or healthcare provider.
Take more than one medication? Open the checker with Isoniazid, Pyrazinamide, Rifampin pre-loaded and add the rest to see overlapping nutrient signals.
Reported nutrient depletions with Isoniazid, Pyrazinamide, Rifampin
Each record below is shown as published in our licensed clinical database, with its evidence rating and citations. Expand a section for food sources and talking points.
NIACIN
Moderate DepletionISONIAZID
Isoniazid can cause a deficiency of pyridoxine, which is needed for conversion of tryptophan to niacin, resulting in a secondary niacin deficiency. Isoniazid also has structural similarities to niacin and might interfere with niacin's conversion to nicotinamide adenine dinucleotide (NAD). Pellagra can occur in people taking isoniazid chronically, especially if dietary niacin intake is low. It can be prevented or reversed with niacin or niacinamide supplements.
Niacin is a B vitamin your body uses to turn food into energy and keep your skin, nerves, and digestion working properly. Isoniazid is thought to reduce niacin in two ways: it can deplete pyridoxine (vitamin B6), which your body needs to convert the amino acid tryptophan into niacin, and it may also block niacin from being activated into its working form. This is a moderate concern, meaning some long-term users, especially those with low dietary niacin, have developed a deficiency condition called pellagra. If you are taking isoniazid for an extended period, it is worth asking your pharmacist or doctor whether a niacin or niacinamide supplement makes sense for you.
What Vitamin B3 (niacin) does & food sources
Niacin supports energy metabolism, skin health, and nervous system function.
Common food sources:
- Poultry, beef, and fish
- Peanuts and legumes
- Fortified grains
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Deficiency is rare in a typical diet. Discuss with your provider before using niacin as a supplement — at pharmacologic doses it behaves like a medication.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
High-dose niacin causes flushing and can affect the liver, blood sugar, and uric acid — it is not a casual supplement.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Caution: Treat high-dose niacin as a medication decision, not a nutrition one.
Learn more about this nutrient: Niacin — uses, safety & interactions
References (6)
- Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams & Wilkins, 1999.
- Ishii N, Nishihara Y. Pellagra encephalopathy among tuberculous patients: its relation to isoniazid therapy. J Neurol Neurosurg Psychiatry 1985;48:628-34. PubMed
- Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
- Darvay A, Basarab T, McGregor JM, Russell-Jones R. Isoniazid induced pellagra despite pyridoxine supplementation. Clin Exp Dermatol 1999;24:167-9. PubMed
- Stratigos JD, Katsambas A. Pellagra: a still existing disease. Br J Dermatol 1977;96:99-106. PubMed
- Bender DA, Russell-Jones R. Isoniazid-induced pellagra despite vitamin B6 supplementation (letter). Lancet 1979;2:1125-6. PubMed
NIACINAMIDE
Moderate DepletionPYRAZINAMIDE
There have been case reports of pellagra after pyrazinamide use which responded to niacinamide supplementation.
Pyrazinamide, one of the drugs in this combination therapy, appears to block how the body uses niacinamide, a B vitamin that helps convert food into energy and keeps skin and nerves healthy. Rather than simply flushing it out, pyrazinamide seems to interfere with niacinamide's activity at a cellular level, and there are real case reports of patients developing pellagra, a serious niacinamide deficiency, while taking it. Because the rating here is moderate, this is worth paying attention to, especially for anyone on long-term treatment. Ask your pharmacist or doctor whether a niacinamide supplement makes sense for you.
What Vitamin B3 (niacin) does & food sources
Niacin supports energy metabolism, skin health, and nervous system function.
Common food sources:
- Poultry, beef, and fish
- Peanuts and legumes
- Fortified grains
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Deficiency is rare in a typical diet. Discuss with your provider before using niacin as a supplement — at pharmacologic doses it behaves like a medication.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
High-dose niacin causes flushing and can affect the liver, blood sugar, and uric acid — it is not a casual supplement.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Caution: Treat high-dose niacin as a medication decision, not a nutrition one.
Learn more about this nutrient: Niacinamide — uses, safety & interactions
References (1)
- Jorgensen J. Pellagra probably due to pyrazinamide: development during combined chemotherapy of tuberculosis. Int J Dermatol 1983;22:44-5. PubMed
VITAMIN B6
Moderate DepletionISONIAZID
Isoniazid interacts with vitamin B6 to form an inactive hydrazine, which inhibits pyridoxal kinase and increases vitamin B6 excretion in the urine. This depletes body stores of vitamin B6 and can lead to peripheral neuritis. It is rare in people receiving up to 5 mg/kg daily isoniazid. With higher doses of isoniazid, consider vitamin B6 supplements, 40-250 mg daily, especially in people with a history of seizures, and in those with other risk factors for neuropathies, including malnutrition, uremia, diabetes, alcoholism, or liver disease. For information on foods that are rich in vitamin B6, see our chart.
Isoniazid, one of the main drugs in tuberculosis treatment, has a well-known chemical interaction with vitamin B6, a nutrient your nerves and brain depend on to work properly. The drug essentially traps vitamin B6 in a form the body cannot use, then flushes the excess out through the urine, gradually drawing down your body's reserves. This is rated a moderate concern, so while most people on standard doses do fine, those on higher doses or with conditions like diabetes, poor nutrition, or kidney disease may be at greater risk for nerve symptoms. It is worth asking your pharmacist or doctor whether a B6 supplement makes sense for you.
What Vitamin B6 does & food sources
Vitamin B6 is involved in protein metabolism, neurotransmitter production, and red blood cell formation.
Common food sources:
- Poultry and fish
- Potatoes and starchy vegetables
- Bananas
- Fortified cereals
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
With some medications (for example, isoniazid), B6 is intentionally co-prescribed — follow your prescriber's plan. Otherwise, ask whether testing or supplementation is appropriate if you have symptoms like numbness or tingling.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Paradoxically, long-term high-dose B6 can itself cause nerve symptoms — this is a nutrient where more is definitely not better.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Caution: Avoid high-dose B6 without medical guidance; sustained high intakes can cause neuropathy.
Learn more about this nutrient: Vitamin B6 — uses, safety & interactions
References (5)
- Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams & Wilkins, 1999.
- Matsui MS, Rozovski SJ. Drug-nutrient interaction. Clin Ther 1982;4:423-40.
- Bass JB, Farer LS, Hopewell PC, et al. Treatment of tuberculosis and tuberculosis infection in adults and children. Am J Respir Crit Care Med 1994;149:1359-74..
- Pellock JM, Howell J, Kendig EI Jr, et al. Pyridoxine deficiency in children treated with isoniazid. Chest 1985;87:658-61. PubMed
- Snider DE Jr. Pyridoxine supplementation during isoniazid therapy. Tubercle 1980;61:191-6. PubMed
VITAMIN D
Moderate DepletionRIFAMPIN (Rifadin)
Rifampin increases hepatic metabolism of 25-hydroxy-vitamin D, reducing its plasma levels. This can contribute to osteomalacia after prolonged therapy (>1 year), especially if vitamin D intake is low. However, if isoniazid (INH, Nydrazid) is taken concurrently with rifampin there doesn't seem to be any change in vitamin D status. This may be because the enzyme-inducing effects on rifampin are canceled out by the enzyme-inhibiting effects of isoniazid. For information on foods that are rich in vitamin D, see our chart.
Vitamin D is something your bones, muscles, and immune system genuinely depend on, so it is worth keeping an eye on here. Rifampin speeds up the liver's breakdown of vitamin D, which can gradually lower the amount circulating in your body. Interestingly, when isoniazid is taken alongside rifampin, as it often is in tuberculosis treatment, research suggests the two drugs may actually cancel each other out on this effect, leaving vitamin D levels relatively unchanged. Still, because this is rated moderate and long-term therapy can matter, it is a reasonable thing to bring up with your pharmacist or doctor, especially if your diet is low in vitamin D.
What Vitamin D does & food sources
Vitamin D helps the body absorb calcium and supports bone, muscle, and immune health.
Common food sources:
- Fatty fish (salmon, mackerel)
- Fortified milk and cereals
- Egg yolks
- Sunlight exposure (the main natural source)
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
A 25-hydroxyvitamin D blood test is the standard way to assess status — ask whether it is appropriate if you take an associated medication long-term, have limited sun exposure, or have bone concerns.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Vitamin D dosing varies a lot between people; some medications change how vitamin D is processed. Your provider can target a dose to your level instead of guessing.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Caution: Vitamin D is fat-soluble and can accumulate — very high doses over time can cause harm, so follow a clinician-guided plan.
Learn more about this nutrient: Vitamin D — uses, safety & interactions
References (5)
- Williams SE, Wardman AG, Taylor GA, et al. Long term study of the effect of rifampicin and isoniazid on vitamin D metabolism. Tubercle 1985;66:49-54. PubMed
- Kovacs CS, Jones G, Yendt ER. Primary hyperparathyroidism masked by antituberculous therapy-induced vitamin D deficiency. Clin Endocrinol (Oxf) 1994;41:831-8. PubMed
- Perry W, Erooga MA, Brown J, Stamp TC. Calcium metabolism during rifampicin and isoniazid therapy for tuberculosis. J R Soc Med 1982;75:533-6. PubMed
- Shah SC, Sharma RK, Hemangini, Chitle AR. Rifampicin induced osteomalacia. Tubercle 1981;62:207-9. PubMed
- Brodie MJ, Boobis AR, Hillyard CJ, et al. Effect of rifampicin and isoniazid on vitamin D metabolism. Clin Pharmacol Ther 1982;32:525-30. PubMed
VITAMIN K
Moderate DepletionRIFAMPIN (Rifadin)
There are occasional reports of vitamin K deficiency associated with rifampin therapy, leading to prolonged clotting times and, in one case, a cerebral bleed. Suggested mechanisms include reduced intestinal absorption of vitamin K, destruction of vitamin K-producing intestinal bacteria, and interference with enzymes that regenerate vitamin K from its inactive metabolite. Symptomatic vitamin K deficiency is most likely to occur in people with poor dietary intake or other contributory factors. For information on foods that are rich in vitamin K, see our chart.
Rifampin, one of the antibiotics in this combination, can interfere with vitamin K, the nutrient your body uses to form blood clots and stop bleeding. It may do this in a few ways: reducing how well your gut absorbs vitamin K, disrupting the intestinal bacteria that naturally produce it, and interfering with the enzymes that recycle vitamin K back into its active form. Most people do well, but if your diet is low in vitamin K or you have other risk factors, your doctor or pharmacist may want to keep a closer eye on your clotting function during treatment.
What Vitamin K does & food sources
Vitamin K is required for normal blood clotting and contributes to bone health.
Common food sources:
- Leafy green vegetables (spinach, kale, broccoli)
- Vegetable oils
- Fermented foods like natto
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
If you take warfarin, vitamin K intake is a central part of your therapy — consistency matters more than avoidance. Discuss any planned change in vitamin K intake (diet or supplements) with the clinic that manages your INR.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Never start or stop a vitamin K supplement on your own if you take warfarin — it directly changes how the medication works.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Caution: Vitamin K interacts with warfarin: keep intake consistent and involve your anticoagulation clinic in any change.
Learn more about this nutrient: Vitamin K — uses, safety & interactions
References (2)
- Kobayashi K, Haruta T, Maeda H, et al. Cerebral hemorrhage associated with vitamin K deficiency in congenital tuberculosis treated with isoniazid and rifampin. Pediatr Infect Dis J 2002;21:1088-90. PubMed
- Van Steenbergen W, Vermylen J. Reversible hypoprothrombinemia in a patient with primary biliary cirrhosis treated with rifampicin. Am J Gastroenterol 1995;90:1526-8.
This tool is educational and is not a substitute for professional medical advice. An association is not a diagnosis and does not mean a deficiency will occur. Always talk to your pharmacist or healthcare provider before starting, stopping, or changing any medication or supplement.
Disclaimer: This checker finds which nutrients might be depleted by prescription or over-the-counter medications. Each nutrient depletion issue is rated based on clinical significance. Use your own professional judgment prior to making clinical decisions.© 2026 Therapeutic Research Center Licensed records refresh weekly · last updated July 3, 2026.
More about Isoniazid, Pyrazinamide, Rifampin
What drug-induced nutrient depletion means
Some medications can, over time, lower the levels of certain vitamins, minerals, or other nutrients — through reduced absorption, increased loss, or changes in how the body uses them.
Association is not deficiency
An entry here means a depletion has been reported or studied — not that it happens to everyone, or that you are deficient. Dose, duration, diet, and your own health all matter.
Evidence varies by pair
Some drug–nutrient links (like metformin and vitamin B12) are well studied; others rest on limited or preliminary research. Each entry shows the evidence rating from our licensed clinical database.
When to ask about labs
If you take an associated medication long-term, ask your healthcare provider whether monitoring is appropriate for you. Not everyone needs testing — your provider can weigh your dose, duration, and symptoms.
Don't self-supplement blindly
Supplements are not risk-free: some can interact with medications, and some (like potassium or magnesium) can be risky with kidney disease. Talk to your pharmacist before adding anything.
Never stop a medication over this
These medications are prescribed for good reasons, and the benefit usually far outweighs a manageable nutrient consideration. Any change belongs in a conversation with your prescriber.
Food first, usually
For many nutrients, a varied diet covers the gap. Each entry lists common food sources; a supplement is a decision to make with your pharmacist or provider, not a default.
Isoniazid, Pyrazinamide, Rifampin & nutrients: FAQs
Does Isoniazid, Pyrazinamide, Rifampin deplete NIACIN?
Should I take a supplement because I take Isoniazid, Pyrazinamide, Rifampin?
Should I stop taking Isoniazid, Pyrazinamide, Rifampin?
Where does this information come from?
Questions about Isoniazid, Pyrazinamide, Rifampin and your nutrition?
Ask a licensed pharmacist — free, no appointment needed.
Sources & How We Checked
Nutrient depletion records for Isoniazid, Pyrazinamide, Rifampin are evidence-graded and sourced from the Natural Medicines database, and are displayed as published with their citations.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for drug-induced nutrient depletions, supplements, and interactions — the basis for this page.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for medication overviews across the site.
Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.