NutriStack
Trimethoprim-Sulfamethoxazole and Vitamin B9, a caution.
Trimethoprim is a folate antagonist that can lower host folate stores during prolonged therapy, particularly in patients with marginal folate intake, pregnancy, or hematologic disease. Folic acid (Vitamin B9) supplementation prevents megaloblastic anemia and is recommended in long courses. Trimethoprim's selectivity for bacterial dihydrofolate reductase means folate supplementation does not meaningfully reduce antibacterial activity in most clinical settings.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
From the interaction database
What the row says.
Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.
At a glance
- Substances
- Trimethoprim-Sulfamethoxazole and Vitamin B9
- Pair type
- Caution
- Evidence (highest tier)
- Moderate
- Source citations
- 2 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Moderate evidence
Caution
What is happening. Trimethoprim is a folate antagonist that can lower host folate stores during prolonged therapy, particularly in patients with marginal folate intake, pregnancy, or hematologic disease. Folic acid (Vitamin B9) supplementation prevents megaloblastic anemia and is recommended in long courses. Trimethoprim's selectivity for bacterial dihydrofolate reductase means folate supplementation does not meaningfully reduce antibacterial activity in most clinical settings.
Mechanism. Trimethoprim inhibits bacterial dihydrofolate reductase preferentially but can affect host folate metabolism over time. Folic acid (or folinic acid) replenishes host folate stores and prevents megaloblastic anemia.
Recommendation. Consider folic acid supplementation during prolonged TMP-SMX therapy, in pregnancy, or in patients with hematologic disease. Standard supplemental doses (400 to 1000 mcg per day) are appropriate. Folinic acid is preferred if a significant deficiency develops.
Stack Score
How this pair moves the number.
Effect on the composite score
If both Trimethoprim-Sulfamethoxazole and Vitamin B9 are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
Check your full routine
One pair was the worked example. NutriStack runs every pair in your stack at once.
Drop in your supplements and prescriptions and the public database surfaces every interaction, synergy, timing rule, and contraindication, every one linked to its primary source.