NutriStack
Methotrexate and Vitamin B9, a synergy.
Vitamin B9 supplementation reduces common methotrexate side effects such as mouth sores, nausea, elevated liver enzymes, and blood-count problems in rheumatologic use. Methotrexate is an antifolate drug, so folate support is often part of safe long-term therapy. The benefit applies to low-dose weekly methotrexate regimens, not high-dose oncology protocols unless the oncology team directs it.
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
- Methotrexate and Vitamin B9
- Pair type
- Synergy
- Evidence (highest tier)
- Strong
- Source citations
- 2 sources
- Stack Score effect
- +2 to your Stack Score (per scored synergy row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Synergy · Strong evidence
Synergy
What is happening. Vitamin B9 supplementation reduces common methotrexate side effects such as mouth sores, nausea, elevated liver enzymes, and blood-count problems in rheumatologic use. Methotrexate is an antifolate drug, so folate support is often part of safe long-term therapy. The benefit applies to low-dose weekly methotrexate regimens, not high-dose oncology protocols unless the oncology team directs it.
Mechanism. Methotrexate inhibits folate-dependent pathways including dihydrofolate reductase-linked one-carbon metabolism. Supplemental folate replenishes normal-cell folate pools and reduces mucosal, hepatic, and hematologic toxicity while generally preserving methotrexate's anti-inflammatory benefit in rheumatoid arthritis.
Recommendation. Use Vitamin B9 only in the schedule your prescriber recommends, commonly daily folic acid or a weekly folate dose away from methotrexate. Do not use folate to self-treat severe mouth sores, fever, bruising, or shortness of breath; those symptoms need urgent clinical review. Keep routine blood-count and liver-test monitoring.
Sources (2)
- Shea B, Swinden MV, Tanjong Ghogomu E, Ortiz Z, Katchamart W, Rader T, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev. 2013;2013(5):CD000951. PMID 23728635
- van Ede AE, Laan RF, Rood MJ, Huizinga TW, van de Laar MA, van Denderen CJ, et al. Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2001;44(7):1515-1524. PMID 11465701
Stack Score
How this pair moves the number.
Effect on the composite score
If both Methotrexate and Vitamin B9 are in the same stack, this pair applies +2 to your Stack Score (per scored synergy 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.