Sulfamethoxazole, Trimethoprim & Nutrient Depletion
Also searched as Bactrim, Bactrim DS, Cotrim DS. What the clinical evidence reports, what it may mean, and what to discuss with your pharmacist.
Sulfamethoxazole, Trimethoprim has been associated with depletion of BIOTIN, FOLIC ACID, RIBOFLAVIN and THIAMINE and 3 more. This does not mean a deficiency will occur — it means these are worth knowing about and, if you take Sulfamethoxazole, Trimethoprim long-term, worth raising with your pharmacist or healthcare provider.
Take more than one medication? Open the checker with Sulfamethoxazole, Trimethoprim pre-loaded and add the rest to see overlapping nutrient signals.
Reported nutrient depletions with Sulfamethoxazole, Trimethoprim
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.
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BIOTIN
Insignificant DepletionANTIBIOTIC DRUGS
Interference with the normal gastrointestinal flora by antibiotics may reduce bacterial synthesis of biotin. Although some bacterially-synthesized biotin can be absorbed from the lower intestine, this appears to contribute less than 20% of a person's daily requirement for biotin. Therefore it's unlikely that antibiotics would contribute to biotin deficiency.
Biotin is a B vitamin your body uses to convert food into energy and keep your hair, skin, and nails healthy. The thinking here is that antibiotics like sulfamethoxazole-trimethoprim can disrupt the normal bacteria living in your gut, and those bacteria do produce a small amount of biotin. That said, clinical research has not shown that this actually leads to any meaningful drop in biotin levels, and the rating for this combination is insignificant. Most people taking this antibiotic do not need to worry about biotin, but if you have questions your pharmacist is always a good place to start.
Learn more about this nutrient: Biotin — uses, safety & interactions
References (4)
- Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams & Wilkins, 1999.
- Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev 1997;6:S43-5. 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
- Grundy WE, Freed M, Johnson H.C., et al. The effect of phthalylsulfathiazole (sulfathalidine) on the excretion of B-vitamins by normal adults. Arch Biochem. 1947 Nov;15:187-94.
FOLIC ACID
Insignificant DepletionANTIBIOTIC DRUGS
Antibiotic therapy can disrupt the normal gastrointestinal (GI) flora, interfering with enterohepatic recirculation (reabsorption) of folic acid. The normal GI flora also synthesizes and consumes folic acid, which may also be disrupted by antibiotics. Folic acid synthesized by GI bacteria can be absorbed in the large intestine, but the amount synthesized and absorbed is variable. For instance, it can depend on dietary fiber intake and gastric pH; hypochlorhydria causes bacterial overgrowth and increased folate synthesis. In most people it's unlikely that a course of antibiotics will reduce folic acid levels significantly, and therefore supplements are unnecessary. For information on foods that are rich in folate, see our chart.
Folic acid is a B vitamin your body uses to make new cells and keep your DNA in good shape. Trimethoprim-sulfamethoxazole works partly by blocking folate pathways in bacteria, and there is also a theoretical concern that antibiotics can disturb the gut bacteria that normally help recycle folate in the intestines. In practice, though, the evidence rates this as insignificant for most people taking a standard course, so supplements are not routinely needed. If you have questions about your diet or a longer treatment, it is always fine to check in with your pharmacist.
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 (5)
- Gorbach SL. Bengt E. Gustafsson memorial lecture. Function of the normal human microflora. Scand J Infect Dis Suppl 1986;49:17-30.
- Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams & Wilkins, 1999.
- Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev 1997;6:S43-5. 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
- Russell RM, Krasinski SD, Samloff IM, et al. Folic acid malabsorption in atrophic gastritis: possible compensation by bacterial folate synthesis. Gastroenterology 1986;91:1476-82. PubMed
RIBOFLAVIN
Insignificant DepletionANTIBIOTIC DRUGS
Interference with the normal gastrointestinal flora by antibiotics may reduce bacterial synthesis of riboflavin. However, this synthesis doesn't seem to significantly contribute to the body's supply of riboflavin, which is primarily obtained from dietary sources. Riboflavin supplements aren't necessary during antibiotic therapy.
Riboflavin, sometimes called vitamin B2, helps your body turn food into energy and keeps your skin and nervous system healthy. Trimethoprim-sulfamethoxazole is an antibiotic, and antibiotics can disrupt the helpful bacteria living in your gut that normally produce small amounts of riboflavin. That said, your gut bacteria contribute very little to your overall riboflavin supply since most of it comes straight from the foods you eat, so this interaction is considered insignificant for the vast majority of people. No extra riboflavin is needed during a typical course of this antibiotic, but feel free to ask your pharmacist if you have questions.
What Vitamin B2 (riboflavin) does & food sources
Riboflavin helps the body produce energy and process other B vitamins.
Common food sources:
- Dairy products and eggs
- Lean meats
- Fortified grains
- Green vegetables
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Deficiency is uncommon with a varied diet; ask your provider if you have persistent mouth-corner cracking, sore tongue, or unexplained fatigue on a long-term associated medication.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Riboflavin is water-soluble and excess is excreted (it turns urine bright yellow — harmless).
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.
Learn more about this nutrient: Riboflavin — uses, safety & interactions
References (3)
- Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev 1997;6:S43-5. 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
- McCormick DB. Riboflavin. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams & Wilkins, 1999. pg.391-9.
THIAMINE
Insignificant DepletionANTIBIOTIC DRUGS
Interference with the normal gastrointestinal flora by antibiotics may reduce bacterial synthesis of thiamine. However, the majority of the daily thiamine requirement is obtained from the diet, rather than synthesis by the GI flora. Therefore this isn't likely to be clinically significant, and thiamine supplements aren't necessary.
Thiamine is a B vitamin your body uses to turn food into energy and keep your nerves working properly. The thinking here is that antibiotics like sulfamethoxazole/trimethoprim can shift the normal bacteria living in your gut, and those bacteria do produce small amounts of thiamine. In practice, though, your diet supplies the vast majority of the thiamine your body needs, so any effect from the medication is considered insignificant. Most people taking this antibiotic have nothing to worry about on this front, but if you have questions about your nutrition while on any medication, your pharmacist or doctor is a great first stop.
What Vitamin B1 (thiamine) does & food sources
Thiamine helps convert food into energy and is essential for nerve and heart function.
Common food sources:
- Whole grains and fortified cereals
- Pork
- Beans and lentils
- Nuts and seeds
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Ask about thiamine if you take an associated medication (for example, a long-term loop diuretic in heart failure) and have symptoms like fatigue or worsening heart failure control — this is an area your care team can weigh.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Thiamine is water-soluble and generally low-risk, but supplementing to treat a suspected problem should still be clinician-guided so the real cause is not missed.
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.
Learn more about this nutrient: Thiamine — uses, safety & interactions
References (1)
- Goldin BR, Lichtenstein AH, Gorbach SL. Nutritional and metabolic roles of intestinal flora. In: Shils ME, Olson JA, Shike M, eds. Modern Nutrition in Health and Disease, 8th ed. Malvern, PA: Lea & Febiger, 1994.
VITAMIN B12
Insignificant DepletionANTIBIOTIC DRUGS
Disruption of the normal gastrointestinal (GI) flora may interrupt enterohepatic recirculation of vitamin B12 and increase fecal excretion. Vitamin B12 is also synthesized by the GI flora, but mainly in the colon where absorption is poor. The majority of bacterially-synthesized vitamin B12 is therefore excreted in the feces and does not significantly contribute to the body's store of vitamin B12. The effects of antibiotics on gastrointestinal bacteria are unlikely to have clinically significant effects on vitamin B12 levels. In people with bacterial overgrowth of the small bowel, antibiotics such as metronidazole (Flagyl) can actually improve vitamin B12 status. An increased bacterial load can bind significant amounts of vitamin B12 in the gut, preventing its absorption.
Vitamin B12 keeps your nerves working properly and helps your body make healthy red blood cells. Sulfamethoxazole-trimethoprim is an antibiotic, and antibiotics can shift the balance of bacteria living in your gut. In theory, that shift might slightly reduce how much B12 your body recycles, but for most people taking this medication the real-world effect on B12 levels is considered insignificant. No extra B12 is needed for the average course of treatment, though if you have questions about your own situation your pharmacist is a great place to start.
What Vitamin B12 does & food sources
Vitamin B12 supports red blood cell formation, nerve function, and DNA synthesis.
Common food sources:
- Meat, poultry, and fish
- Eggs and dairy products
- Fortified cereals and nutritional yeast
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
If you take an associated medication long-term, ask your healthcare provider whether checking a vitamin B12 level (sometimes with methylmalonic acid) is appropriate — especially if you notice fatigue, numbness, tingling, or memory changes.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
B12 status is easy to check and low levels are usually straightforward to address, so testing before supplementing is often the sensible order. High-dose folic acid can mask a B12 deficiency, which is one reason B12 and folate questions are best sorted out together with your provider.
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: B12 deficiency can look like other conditions — do not self-diagnose from symptoms alone.
Learn more about this nutrient: Vitamin B12 — uses, safety & interactions
References (3)
- Gorbach SL. Bengt E. Gustafsson memorial lecture. Function of the normal human microflora. Scand J Infect Dis Suppl 1986;49:17-30.
- Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev 1997;6:S43-5. PubMed
- Goldin BR, Lichtenstein AH, Gorbach SL. Nutritional and metabolic roles of intestinal flora. In: Shils ME, Olson JA, Shike M, eds. Modern Nutrition in Health and Disease, 8th ed. Malvern, PA: Lea & Febiger, 1994.
VITAMIN B6
Insignificant DepletionANTIBIOTIC DRUGS
Some sources suggest that destruction of the normal gastrointestinal flora by antibiotics can decrease production and plasma levels of vitamin B6. However, there is no evidence that the gastrointestinal flora is a significant source of vitamin B6 in humans. Supplementation with vitamin B6 is not necessary during antibiotic therapy. For information on foods that are rich in vitamin B6, see our chart.
Vitamin B6 is something your body uses to turn food into energy and keep your nervous system running smoothly. There has been a theoretical idea that antibiotics like sulfamethoxazole/trimethoprim could reduce B6 by disrupting the bacteria that live in your gut, since those bacteria can produce small amounts of the vitamin. The catch is that gut bacteria are not actually considered a meaningful source of B6 for people, so this concern has not held up. For most folks taking this antibiotic, this is a non-issue and no extra B6 is needed.
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 (3)
- Gorbach SL. Bengt E. Gustafsson memorial lecture. Function of the normal human microflora. Scand J Infect Dis Suppl 1986;49:17-30.
- Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev 1997;6:S43-5. PubMed
- Goldin BR, Lichtenstein AH, Gorbach SL. Nutritional and metabolic roles of intestinal flora. In: Shils ME, Olson JA, Shike M, eds. Modern Nutrition in Health and Disease, 8th ed. Malvern, PA: Lea & Febiger, 1994.
VITAMIN K
Moderate DepletionANTIBIOTIC DRUGS
Vitamin K produced by intestinal bacteria is absorbed from the ileum. This contribution to overall vitamin K status is unclear, and likely varies. Destruction of vitamin K-producing bacteria by antibiotics can sometimes lead to vitamin K deficiency, prolonging clotting times and increasing bleeding risk. It's suggested that antibiotics such as cefamandole that are secreted into the bile in large amounts have a greater effect on vitamin K-producing bacteria. Also, some cephalosporins have a methylthiotetrazole side chain that may interfere with vitamin K activity, directly inhibiting clotting factor production in the liver. These cephalosporins include cefamandole, cefoperazone, cefmetazole, and cefotetan. This interaction is most likely to occur with prolonged antibiotic therapy (10 days or more) in people with poor dietary vitamin K intake. Vitamin K supplements aren't necessary for otherwise healthy people taking short courses of antibiotics. For information on foods that are rich in vitamin K, see our chart.
Vitamin K is something your body needs to form blood clots and keep bleeding under control. Sulfamethoxazole-trimethoprim is an antibiotic, and antibiotics can reduce the friendly bacteria living in your gut that naturally produce a portion of your vitamin K supply. For a short course of this medication, that is generally not a concern for healthy people eating reasonably well. If you are on a longer course, say ten days or more, or if your diet is already low in vitamin K-rich foods like leafy greens, it is worth mentioning to your pharmacist or doctor so they can decide whether any monitoring or adjustments make sense for you.
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 (8)
- Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev 1997;6:S43-5. PubMed
- Conly JM, Stein K, Worobetz L, Rutledge-Harding S. The contribution of vitamin K2 (menaquinones) produced by the intestinal microflora to human nutritional requirements for vitamin K. Am J Gastroenterol 1994;89:915-23.
- Goldin BR, Lichtenstein AH, Gorbach SL. Nutritional and metabolic roles of intestinal flora. In: Shils ME, Olson JA, Shike M, eds. Modern Nutrition in Health and Disease, 8th ed. Malvern, PA: Lea & Febiger, 1994.
- Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
- Haubenstock A, Schmidt P, Zazgornik J, Balcke P, Kopsa H. Hypoprothrombobinaemic bleeding associated with ceftriaxone. Lancet 1983;1:1215-6.
- Hooper CA, Haney BB, Stone HH. Gastrointestinal bleeding due to vitamin K deficiency in patients on parenteral cefamandole. Lancet 1980;1:39-40. PubMed
- Bhat RV, Deshmukh CT. A study of Vitamin K status in children on prolonged antibiotic therapy. Indian Pediatr 2003;40:36-40.
- Sattler FR, Weitekamp MR, Ballard JO. Potential for bleeding with the new beta-lactam antibiotics. Ann Intern Med 1986;105:924-31. PubMed
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 Sulfamethoxazole, Trimethoprim
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.
Sulfamethoxazole, Trimethoprim & nutrients: FAQs
Does Sulfamethoxazole, Trimethoprim deplete BIOTIN?
Should I take a supplement because I take Sulfamethoxazole, Trimethoprim?
Should I stop taking Sulfamethoxazole, Trimethoprim?
Where does this information come from?
Questions about Sulfamethoxazole, Trimethoprim and your nutrition?
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Sources & How We Checked
Nutrient depletion records for Sulfamethoxazole, Trimethoprim 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.