Sulfasalazine & Nutrient Depletion
Also searched as SAS, Azulfidine EN-Tabs, Azulfidine. What the clinical evidence reports, what it may mean, and what to discuss with your pharmacist.
Sulfasalazine has been associated with depletion of FOLIC ACID. This does not mean a deficiency will occur — it means these are worth knowing about and, if you take Sulfasalazine long-term, worth raising with your pharmacist or healthcare provider.
Take more than one medication? Open the checker with Sulfasalazine pre-loaded and add the rest to see overlapping nutrient signals.
Reported nutrient depletions with Sulfasalazine
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.
FOLIC ACID
Moderate DepletionSULFASALAZINE (Azulfidine)
Sulfasalazine competitively inhibits absorption of folic acid in the intestine. It also interferes with the breakdown of dietary folate to its absorbable form, and can cause hemolysis, which increases folate requirements for formation of new red blood cells. Long-term sulfasalazine therapy can cause reduced serum and red blood cell folate levels and hyperhomocysteinemia. Occasionally, megaloblastic anemia develops, usually with high doses of sulfasalazine ( >2 grams/day), and when there are other factors contributing to folate deficiency. Reduced folate levels might contribute to the increased risk of colon cancer and colonic mucosal dysplasia seen in people with ulcerative colitis. Advise patients on chronic sulfasalazine therapy to increase their dietary folate intake, and to take a supplement if they have any other condition which could also contribute to deficiency. For information on foods that are rich in folate, see our chart.
Folic acid is a B vitamin your body needs to build healthy red blood cells and keep your DNA working properly. Sulfasalazine works against folate in two ways: it blocks absorption of folic acid in the gut, and it also interferes with the step that converts dietary folate into a form your intestine can actually take in. For people on long-term or higher-dose therapy, this is a real enough concern that some patients end up needing a supplement, though not everyone will. If you have been taking sulfasalazine for a while, it is worth asking your doctor or pharmacist whether your folate levels should be checked.
What Folic acid (folate) does & food sources
Folate is needed for cell division, red blood cell formation, and healthy fetal development.
Common food sources:
- Leafy green vegetables
- Beans, lentils, and peas
- Fortified grains and cereals
- Citrus fruits
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Ask your provider whether folate monitoring or supplementation is appropriate for you — this matters most before and during pregnancy, and with long-term use of certain seizure or arthritis medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Folate needs are individual. With some medications (for example, methotrexate), folic acid is often prescribed deliberately on a specific schedule — follow your prescriber's instructions rather than adding your own.
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: High-dose folic acid can mask vitamin B12 deficiency, so the two are often evaluated together.
Learn more about this nutrient: Folic Acid — uses, safety & interactions
References (10)
- Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams & Wilkins, 1999.
- Krogh-Jensen M, Ekelund S, Svendsen L. Folate and homocysteine status and haemolysis in patients treated with sulphasalazine for arthritis. Scand J Clin Lab Invest 1996;56:421-9. PubMed
- Zimmerman J. Drug interactions in intestinal transport of folic acid and methotrexate. Further evidence for the heterogeneity of folate transport in the human small intestine. Biochem Pharmacol 1992;44:1839-42. PubMed
- Halsted CH, Gandhi G, Tamura T. Sulfasalazine inhibits the absorption of folates in ulcerative colitis. New Engl J Med 1981;305:1513-7. PubMed
- Longstreth GF, Green R. Folate status in patients receiving maintenance doses of sulfasalazine. Arch Int Med 1983;143:902-4. DOI
- Logan EC, Williamson LM, Ryrie DR. Sulphasalazine associated pancytopenia may be caused by acute folate deficiency. Gut 1986;27:868-72. PubMed
- Grieco A, Caputo S, Bertoli A, et al. Megaloblastic anemia due to sulphasalazine responding to drug withdrawal alone. Postgrad Med J 1986;62:307-8.
- Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs 1985;30:145-55. PubMed
- Prouse PJ, Shawe D, Gumpel JM. Macrocytic anemia in patients treated with sulfasalazine for rheumatoid arthritis. BMJ 1986;293:1407.
- Lashner BA, Heidenreich PA, Su GL, et al. Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. Gastroenterology 1989;97:255-9. DOI
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 Sulfasalazine
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.
Sulfasalazine & nutrients: FAQs
Does Sulfasalazine deplete FOLIC ACID?
Should I take a supplement because I take Sulfasalazine?
Should I stop taking Sulfasalazine?
Where does this information come from?
Questions about Sulfasalazine and your nutrition?
Ask a licensed pharmacist — free, no appointment needed.
Sources & How We Checked
Nutrient depletion records for Sulfasalazine 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.