NutriStack
Methylfolate and Trimethoprim-Sulfamethoxazole, a caution.
Trimethoprim inhibits dihydrofolate reductase and can cause folate deficiency with prolonged use, particularly in people with marginal folate status, pregnancy, or chronic illness. Methylfolate supplementation can correct this deficiency without interfering with the antibiotic's antibacterial activity, since trimethoprim is highly selective for bacterial dihydrofolate reductase. However, very high folate intake near antibiotic dosing has theoretical potential to reduce antibacterial efficacy in some infections.
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.
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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
- Methylfolate and Trimethoprim-Sulfamethoxazole
- 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 inhibits dihydrofolate reductase and can cause folate deficiency with prolonged use, particularly in people with marginal folate status, pregnancy, or chronic illness. Methylfolate supplementation can correct this deficiency without interfering with the antibiotic's antibacterial activity, since trimethoprim is highly selective for bacterial dihydrofolate reductase. However, very high folate intake near antibiotic dosing has theoretical potential to reduce antibacterial efficacy in some infections.
Mechanism. Trimethoprim selectively inhibits bacterial dihydrofolate reductase but can also weakly affect host folate metabolism in long courses. Methylfolate bypasses the dihydrofolate reductase step entirely by providing the active 5-methyltetrahydrofolate form.
Recommendation. Methylfolate supplementation is generally safe during trimethoprim-sulfamethoxazole therapy and is recommended for prolonged courses, pregnancy, or pre-existing folate deficiency. Separate doses by at least 2 hours to be conservative.
Minimum separation. 120
Stack Score
How this pair moves the number.
Effect on the composite score
If both Methylfolate and Trimethoprim-Sulfamethoxazole 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.
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