Drug & supplement interaction

Lentinan + Methotrexate

Methotrexate brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 13, 2026
The bottom line No known interaction

We found no known interaction between Lentinan and Methotrexate in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

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Interaction report

Lentinan and Methotrexate

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Methotrexate and Lentinan in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Lentinan safety at a glance

Lentinan overall Use caution Oral mushroom extracts are generally well tolerated, but the injectable medical form should only be used under a doctor's care.
Pregnancy Avoid There is not enough reliable safety information, so it is best to avoid use during pregnancy.
Breastfeeding Avoid Safety while breastfeeding is unknown, so avoiding it is the safer choice.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Methotrexate and Lentinan? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Methotrexate

Interactions in our licensed database are recorded against drug classes, not just single drug names. Methotrexate is filed under 6 classifications — including organic anion-transporting polypeptide substrates (oatp), organic anion transporter 3 (oat3) substrates, hepatotoxic drugs. Lentinan has documented interactions with 8 drug classes — the most serious being cytochrome p450 1a2 (cyp1a2) substrates (moderate), cytochrome p450 2c19 (cyp2c19) substrates (moderate) and cytochrome p450 2d6 (cyp2d6) substrates (moderate) — and none of Methotrexate’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Lentinan Does Interact With Other Medications

Lentinan has 814 moderate known drug interactions in our database — Methotrexate isn’t one of them. If you take anything else, check it against the full list below.

Moderate 814 No known interaction 2,016 (incl. Methotrexate)
Taking anything else?

Check Another of Your Medications Against Lentinan

Covers the 2,830 medications we’ve checked against Lentinan. Pick one to open its full report.

What to actually watch for

No Interaction Found — But Data Suggests Lentinan and Methotrexate May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do. 2 of them are worth acting on rather than waiting out — marked below.

  • Chest pain Worth acting on Additional detail

    Lentinan

    “Parenterally and orally, lentinan seems to be well tolerated. Orally, lentinan has been rarely reported to cause rash, diarrhea, and constipation. Parenterally, lentinan has been reported to cause gastrointestinal cramping, rash, myalgia, and fatigue. Mild thrombocytopenia has also been reported in clinical trials (6).”

    Lentinan · Natural Medicines adverse-effect record, reported in constipation.

    5 sources cited
    1. 96863. Wang H, Cai Y, Zheng Y, Bai Q, Xie D, Yu J. Efficacy of biological response modifier lentinan with chemotherapy for advanced cancer: a meta-analysis. Cancer Med. 2017;6(10):2222-2233. PubMed
    2. 34779. Hazama, S., Watanabe, S., Ohashi, M., Yagi, M., Suzuki, M., Matsuda, K., Yamamoto, T., Suga, Y., Suga, T., Nakazawa, S., and Oka, M. Efficacy of orally administered superfine dispersed lentinan (beta-1,3-glucan) for the treatment of advanced colorectal c
    3. 1107. Gordon M, Guralnik M, Kaneko Y, et al. A phase II controlled study of a combination of the immune modulator, lentinan, with didanosine (ddI) in HIV patients with CD4 cells of 200-500/mm3. J Med 1995;26:193-207.
    4. 6. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
    5. 1111. Wada T, Nishide T, Hatayama K, et al. [A comparative clinical trial with tegafur plus lentinan treatment at two different doses in advanced cancer]. Gan To Kagaku Ryoho 1987;14:2509-11.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • A low platelet count Worth acting on Additional detail

    Lentinan

    “Parenterally, lentinan has been reported to cause mild thrombocytopenia (6).”

    Lentinan · Natural Medicines adverse-effect record, reported in thrombocytopenia.

    1 source cited
    1. 6. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • Joint pain reported in 22.2% of FDA reports for Methotrexate Additional detail

    Lentinan

    “Parenterally, lentinan has been reported to cause joint pain and myalgia.”

    Lentinan · Natural Medicines adverse-effect record, reported in myalgia.

    2 sources cited
    1. 1107. Gordon M, Guralnik M, Kaneko Y, et al. A phase II controlled study of a combination of the immune modulator, lentinan, with didanosine (ddI) in HIV patients with CD4 cells of 200-500/mm3. J Med 1995;26:193-207.
    2. 7267. Gordon M, Bihari B, Goosby E, et al. A placebo-controlled trial of the immune modulator, lentinan, in HIV-positive patients: a phase I/II trial. J Med 1998;29:305-30.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

  • Chills / Fever Additional detail

    Lentinan

    “Parenterally, lentinan has been reported to cause chills, fever, and lymph node swelling.”

    Lentinan · Natural Medicines adverse-effect record, reported in fever.

    1 source cited
    1. 7267. Gordon M, Bihari B, Goosby E, et al. A placebo-controlled trial of the immune modulator, lentinan, in HIV-positive patients: a phase I/II trial. J Med 1998;29:305-30.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • Muscle pain Additional detail

    Lentinan

    Recorded for Lentinan in the same Natural Medicines adverse-effect record shown under Chest pain above.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • Tiredness / A skin rash reported in 6.7% of FDA reports for Methotrexate Additional detail

    Lentinan

    Recorded for Lentinan in the same Natural Medicines adverse-effect record shown under Chest pain above.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

  • Nausea reported in 5.9% of FDA reports for Methotrexate Additional detail

    Lentinan

    “Orally and parenterally, lentinan has been rarely reported to cause diarrhea, nausea, vomiting, and constipation.”

    Lentinan · Natural Medicines adverse-effect record, reported in constipation.

    2 sources cited
    1. 7267. Gordon M, Bihari B, Goosby E, et al. A placebo-controlled trial of the immune modulator, lentinan, in HIV-positive patients: a phase I/II trial. J Med 1998;29:305-30.
    2. 34779. Hazama, S., Watanabe, S., Ohashi, M., Yagi, M., Suzuki, M., Matsuda, K., Yamamoto, T., Suga, Y., Suga, T., Nakazawa, S., and Oka, M. Efficacy of orally administered superfine dispersed lentinan (beta-1,3-glucan) for the treatment of advanced colorectal c

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

  • Diarrhea Additional detail

    Lentinan

    Recorded for Lentinan in the same Natural Medicines adverse-effect record shown under Chest pain above.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

Showing the 10 most notable of 12 shared effects — ranked by how unusual each one is, not just whether both lists mention it.

Reported for Lentinan but not commonly for Methotrexate: constipation and swelling.

Effects for Methotrexate come from the ADVERSE REACTIONS section of its FDA label; effects for Lentinan come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 489,806 voluntary FDA FAERS reports for Methotrexate that mention that effect — a reporting proportion, not an incidence rate and not evidence the drug caused it. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

Overlapping uses

What Methotrexate Is Prescribed For, and What Lentinan Has Been Studied For

These two come up together because they touch the same health topic — not because they do the same job. Methotrexate is a prescription medicine with approved uses on its FDA label. Lentinan is a supplement: what follows is what researchers have looked at it for, and how strong that evidence is.

Methotrexate is prescribed for: Methotrexate treats a wide range of serious conditions. In cancer care, it is used for acute lymphoblastic leukemia, non-Hodgkin lymphoma, osteosarcoma, breast cancer, head and neck cancer, and gestational trophoblastic neoplasia (a rare tumor related to pregnancy). It is also used to prevent and treat meningeal leukemia (cancer affecting the lining of the brain and spinal cord). Outside of cancer, methotrexate is prescribed for adults with rheumatoid arthritis (RA), children with polyarticular juvenile idiopathic arthritis (a form of childhood arthritis), and adults with severe psoriasis that hasn't responded well to other treatments.

Lentinan has been studied for:

  • Lung cancer studied, not established Lentinan has been studied for this. Natural Medicines rates the evidence: Insufficient Reliable Evidence To Rate Read what the research shows

    Lentinan for lung cancer

    Meta-analyses of preliminary clinical research shows that lentinan injection increases the efficacy of chemotherapy in patients with lung cancer. In patients with non-small cell lung cancer, the objective response rate was improved by 31% over chemotherapy alone. However, lentinan did not improve the response to navelbine with cisplatin in a sub-group analysis.

    2 sources cited
    1. 96863. Wang H, Cai Y, Zheng Y, Bai Q, Xie D, Yu J. Efficacy of biological response modifier lentinan with chemotherapy for advanced cancer: a meta-analysis. Cancer Med. 2017;6(10):2222-2233. PubMed
    2. 96865. Yin X, Ying J, Li L, Zhang H, Wang H. A meta-analysis of lentinan injection combined with chemotherapy in the treatment of nonsmall cell lung cancer. Indian J Cancer. 2015;52 Suppl 1:e29-31. PubMed

Effectiveness ratings and the research summaries above are the verbatim record from the Natural Medicines database, which grades evidence from “Effective” down to “Insufficient Reliable Evidence To Rate”. A rating below the top of that scale means researchers have looked at it — not that it works, and never that it can stand in for a prescribed medicine. Do not stop or replace Methotrexate on your own; if you are taking Lentinan for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

From our Q&A

Questions About Lentinan or Methotrexate

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Lentinan or Methotrexate, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Methotrexate

This page covers Lentinan only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Methotrexate page lists 82 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Apple (major), Beer (major), Grapefruit (major) and Siberian Cocklebur (major).

By severity: 7 major · 60 moderate · 15 minor.

From our pharmacist’s overview on the Methotrexate page

“The liver is where methotrexate and supplements clash most. Methotrexate (Rheumatrex, Otrexup, Rasuvo), used for rheumatoid arthritis, psoriasis, and certain cancers, can strain the liver on its own, and 38 of the 82 interacting ingredients on this list add liver risk of their own, alcohol included, which makes this a list to approach…”

Reviewed by 2 · Jul 18, 2026

Open the Methotrexate interaction page

One more smart check

Taking Lentinan as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1 real supplement products containing Lentinan, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Lentinan. Even though Lentinan itself has no known interaction with Methotrexate, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Lentinan and Methotrexate Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Lentinan
Top half

#667 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Methotrexate
Top 5%

#49 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Lentinan reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Lentinan and Methotrexate records this page draws on were last updated July 10, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Supplement

About Lentinan

What is Lentinan?

Lentinan
  • Immune support
  • Used alongside cancer treatment
  • Anti-inflammatory
  • General wellness/tonic
  • Antimicrobial support

Lentinan is a beta-glucan polysaccharide from shiitake mushrooms that is studied mainly as an immune-modulating add-on to cancer chemotherapy, where it is given by injection in a few countries. Evidence for oral supplements is limited, and quality varies widely between products. Talk with your pharmacist or doctor before using it, especially if you have a health condition or are pregnant or breastfeeding.

Lentinula edodes · Marasmiaceae · Fruiting body of the shiitake mushroom (the polysaccharide is extracted from it) · Injection (used in some countries under medical supervision), capsules, tablets, powdered mushroom extracts, oral liquid

An interaction check asks whether these two react with each other — it does not ask whether Lentinan is a good idea for someone in your situation. Here is what our Lentinan record says about it on its own.

Lentinan: dosing

There is no well-established standard dose for oral lentinan or shiitake supplements. Products differ a lot in how much actual beta-glucan they contain, so amounts on labels are not always comparable.If you choose to take an oral supplement, follow the directions on the product label and do not exceed them. The injectable medical form has its own dosing that is determined by a doctor as part of cancer treatment and is not something to manage at home.

From our Lentinan monograph — the full record covers uses, side effects and every documented interaction.

Read the full Lentinan monograph & all interactions
Medication

About Methotrexate

What Is Methotrexate Used For?

Brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex

Methotrexate treats a wide range of serious conditions. In cancer care, it is used for acute lymphoblastic leukemia, non-Hodgkin lymphoma, osteosarcoma, breast cancer, head and neck cancer, and gestational trophoblastic neoplasia (a rare tumor related to pregnancy). It is also used to prevent and treat meningeal leukemia (cancer affecting the lining of the brain and spinal cord).

Outside of cancer, methotrexate is prescribed for adults with rheumatoid arthritis (RA), children with polyarticular juvenile idiopathic arthritis (a form of childhood arthritis), and adults with severe psoriasis that hasn't responded well to other treatments.

Most-Reported Side Effects for Methotrexate

From FAERS, the FDA’s public side-effect reporting system (489,806 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Rheumatoid arthritis 42,798 reports
Arthralgia 40,830 reports
Fatigue 33,049 reports
Nausea 28,999 reports
Joint swelling 25,026 reports
See full Methotrexate drug information
Keep checking

Other Drugs & Lentinan

Browse every other medication we’ve checked against Lentinan — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
814Moderate
0Minor
2,015No known interaction
814 Moderate 2,015 No interaction
Moderate

814 interactions

Showing 60 of 814 moderate interactions — see all 814 on the Lentinan page.

No interaction 2,015 drugs checked — show the list

We also checked Lentinan against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,015 medications checked with no known interaction — see the full Lentinan list.

See the full Lentinan interactions page
See every supplement checked against Methotrexate, ranked by severity
Evidence & sources

Lentinan References

The 19 references that drive our Lentinan monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  2. Gordon M, Guralnik M, Kaneko Y, et al. A phase II controlled study of a combination of the immune modulator, lentinan, with didanosine (ddI) in HIV patients with CD4 cells of 200-500/mm3. J Med 1995;26:193-207.
  3. Yoshiyuki T, Onda M, Tokunaga A, et al. [Treatment for peritoneal dissemination of gastric cancer by intraperitoneal administration of CDDP through Infuse-a-Port]. Gan To Kagaku Ryoho 1994;21:2323-5.
  4. Tari K, Satake I, Nakagomi K, et al. [Effect of lentinan for advanced prostate carcinoma]. Hinyokika Kiyo 1994;40:119-23.
  5. Nishihira T, Akimoto M, Mori S. [Anti-cancer effects of BRMs associated with nutrition in cancer patients]. Gan To Kagaku Ryoho,1988;15:1615-20.
  6. Wada T, Nishide T, Hatayama K, et al. [A comparative clinical trial with tegafur plus lentinan treatment at two different doses in advanced cancer]. Gan To Kagaku Ryoho 1987;14:2509-11.
  7. Taguchi T. Clinical efficacy of lentinan on patients with stomach cancer: end point results of a four-year follow-up survey. Cancer Detect Prev Suppl 1987;1:333-49.
  8. Gordon M, Bihari B, Goosby E, et al. A placebo-controlled trial of the immune modulator, lentinan, in HIV-positive patients: a phase I/II trial. J Med 1998;29:305-30.
  9. Hazama, S., Watanabe, S., Ohashi, M., Yagi, M., Suzuki, M., Matsuda, K., Yamamoto, T., Suga, Y., Suga, T., Nakazawa, S., and Oka, M. Efficacy of orally administered superfine dispersed lentinan (beta-1,3-glucan) for the treatment of advanced colorectal c
  10. Zhang D, Zheng J, Ni M, et al. Comparative efficacy and safety of Chinese herbal injections combined with the FOLFOX regimen for treating gastric cancer in China: a network meta-analysis. Oncotarget. 2017;8(40):68873-68889. PubMed
  11. Wang H, Cai Y, Zheng Y, Bai Q, Xie D, Yu J. Efficacy of biological response modifier lentinan with chemotherapy for advanced cancer: a meta-analysis. Cancer Med. 2017;6(10):2222-2233. PubMed
  12. Yoshino S, Nishikawa K, Morita S, et al. Randomised phase III study of S-1 alone versus S-1 plus lentinan for unresectable or recurrent gastric cancer (JFMC36-0701). Eur J Cancer. 2016;65:164-71. PubMed
  13. Yin X, Ying J, Li L, Zhang H, Wang H. A meta-analysis of lentinan injection combined with chemotherapy in the treatment of nonsmall cell lung cancer. Indian J Cancer. 2015;52 Suppl 1:e29-31. PubMed
  14. Wang JL, Bi Z, Zou JW, Gu XM. Combination therapy with lentinan improves outcomes in patients with esophageal carcinoma. Mol Med Rep. 2012;5(3):745-8. PubMed
  15. Lin Y, Wei Y, Hu X, et al. Evaluation of lentinan effects on cytochrome P450 activity in rats by a cocktail method. Iran J Basic Med Sci. 2019;22(3):296-301.

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Lentinan and Methotrexate Together: Common Questions

Is it safe to take Lentinan with Methotrexate?
We do not list a known interaction between Lentinan and Methotrexate. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Do Lentinan and Methotrexate have any of the same side effects?
Yes — our sources link each of them separately to 10 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.
Are Lentinan and Methotrexate used for the same thing?
They overlap in purpose, which usually means the real question is whether you need both rather than whether they are safe together. This page lists the shared uses and how strong the evidence is for Lentinan in each. That is a conversation for your prescriber, especially if Methotrexate is being adjusted to a target.
How was the Lentinan and Methotrexate combination checked?
Interactions in our licensed database are recorded against drug classes. Methotrexate is filed under 6 classifications, and Lentinan has documented interactions with 8 drug classes — none of Methotrexate's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does Lentinan interact with any other medications?
Yes. Lentinan has 814 documented drug interactions in our database — Methotrexate is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Methotrexate interact with any supplements?
Yes. Methotrexate has documented interactions with 82 supplements in our database — Lentinan is not one of them. The Methotrexate interaction page linked on this page lists every one, ranked by severity.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Where next

Keep Exploring

Lentinan monograph Uses, safety profile, and every drug interaction in one place Methotrexate drug information The full plain-English guide to this medication Methotrexate supplement interactions Every supplement checked against Methotrexate, ranked by severity Supplement interaction checker Check any supplement or product against your medications Browse medications A–Z Every drug we’ve checked against herbs & supplements References The 19 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Methotrexate and Lentinan?

Our pharmacists answer your medication & supplement questions — free.

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.