Rheumatoid Arthritis and Natural Treatment: What Was Measured, and What About Methotrexate

Rheumatoid arthritis (RA) is the only autoimmune disease in which one of the four mushrooms we grow — reishi (Ganoderma lucidum, the lingzhi of Chinese medicine) — has been tested in a randomized human trial. The honest answer: that trial, 65 patients over 24 weeks, missed its primary endpoint — 15% versus 9.1% on placebo, not significant — and the reishi was given together with a separate herbal formula. With methotrexate, adalimumab (Humira) or tofacitinib (Xeljanz), the combination has never been measured in humans.

The kinds of evidence that do exist, from closest to a person to furthest away: one randomized trial in RA patients, plus a second, immunological publication from the same trial; human trials on fatigue, fitness and immune stimulation — in other populations; Cochrane reviews of the drugs themselves, and one study that shows what a measured interaction with a JAK inhibitor looks like; and rodents pointing in both directions — mice in which a molecule from reishi eased arthritis, and mice in which a different beta-glucan set it off. On the combination “mushroom × RA drug” there is no human measurement; with methotrexate there are 3 co-administration studies — in mice and cells only. This page is built around what you are actually asking: what is allowed with your drug, and what was measured on the pain and fatigue you live with.

Do medicinal mushrooms help with rheumatoid arthritis — and what exactly was tested?

One thing was tested: reishi together with the Chinese formula San Miao San, in 65 patients, for 24 weeks. The primary endpoint — ACR20, a 20% improvement by the ACR criteria — was reached by 15% versus 9.1% on placebo, a non-significant difference. Not one immune or inflammatory marker moved. Lion’s mane, cordyceps and turkey tail have not been tested in RA patients at all.

That is not nothing, and it is not much. Of the 13 autoimmune diseases we searched, this is the only randomized human trial with one of the four mushrooms we grow — which makes rheumatoid arthritis the only disease where we can write “tested in humans”. But what was tested missed the endpoint the researchers themselves had set, and the preparation was not reishi alone. We gathered the broader picture across all autoimmune diseases on the medicinal mushrooms and autoimmune disease page, and the general question about joints on do mushrooms help with arthritis. Here we deal with the narrow intersection: RA, the drug you take, and the symptoms you live with.

And the most important thing, before anything else: rheumatoid arthritis is treated with drugs that prevent joint damage that cannot be reversed. A Cochrane review of methotrexate alone versus placebo — 7 trials, 732 participants — found that 15 more out of every 100 patients reached a 50% improvement (ACR50) at one year, and that radiographic progression of damage was lower (RR 0.31). That is what the bar for “works” looks like. None of our four mushrooms has come anywhere near it, and nothing on this page is a reason to change your treatment.

What was measured, in which system — and what came out?

The table sorts your questions by what was measured on them and in which organism. Only one row is a randomized trial of a mushroom in RA patients — and it is negative on the primary endpoint. The drug rows contain no mushroom studies. And the rows that do hold many randomized trials in RA patients belong to omega-3 and diet — which we do not sell.

What exactly did the trial in 65 RA patients find — and why is “reishi is proven against arthritis” wrong?

It found that the primary endpoint was not reached, that no immune marker changed, and that pain and self-assessment improved only in the herbal group — as a secondary measure, against baseline. The authors wrote that the preparation “may have an analgesic effect”, but no anti-inflammatory or immunomodulatory effect was demonstrated. And all of this is reishi together with San Miao San.

What the market claims. “A clinical trial showed that reishi reduces pain in rheumatoid arthritis”, “reishi regulates the immune system in RA patients”. Both sentences cite the same trial, and both skip three facts.

What exactly was measured. In 2007, 65 patients with RA that was active despite DMARD drugs were randomized: 32 received 4 grams of reishi and 2.4 grams of San Miao San a day, 33 received placebo, all in addition to the drugs they were already taking, for 24 weeks; 89% completed. ACR20 — the standard measure of “a 20% improvement” — was reached by 15% versus 9.1%. The immunological publication from the same trial, from 2006, examined CD4, CD8, NK and B cell counts and plasma IP-10, MCP-1, MIG, RANTES, IL-8 and IL-18 at 8 and 24 weeks — no difference between the groups. The only change: IL-18 induced in a test tube from blood cells, outside the body. Side effects: 22 mild events in 13 patients — 8 in the herbal group and 14 on placebo.

Why it does not carry over automatically to “reishi helps”. First: the formula. San Miao San is a separate herbal blend, and neither the improvement in pain nor the absence of side effects can be attributed to reishi alone. Second: the pain that improved is described in the abstract as improving “in the herbal group only” — that is, against baseline within the group, not as a reported difference between the groups — and that is exactly where the placebo effect lives. Third: the same formula was tested in 2008 in rats with induced joint inflammation; injected into the abdominal cavity it reduced pain sensitivity, but swallowed — the way people actually take it — it reduced swelling and redness, and on histology there was less immune-cell infiltration and less cartilage erosion; pain sensitivity it did not reduce.

What can be known today. That in patients who took the preparation for half a year on top of their drugs, no more side effects were seen than on placebo — a small, unplanned safety data point, but a real one. And that there is no evidence at all that reishi changes the course of the disease. What to ask the rheumatologist. Not “does reishi help RA” — the trial answered that — but “is there a reason, in my case and with my drugs, to avoid any supplement”.

Taking methotrexate — can you take medicinal mushrooms with it?

In humans — not measured: 0 interaction or pharmacokinetic studies between methotrexate and any of the four mushrooms; in mice and cells — 3 co-administration studies, none in a patient. What is known concerns the liver: methotrexate requires liver-enzyme monitoring, folic acid reduced enzyme elevation by 76.9% in relative terms, and drinking above 21 units of alcohol a week raised the risk. And reishi has two reports of liver injury. A question for the rheumatologist, with the data in hand.

What was tested on methotrexate itself. A 2014 Cochrane review found that methotrexate at 5–25 mg a week works — and that it is not free of side effects: 16% of patients stopped because of side effects versus 8% on placebo, and 45% versus 15% reported some side effect in the first 12 weeks. Another Cochrane review, from 2013, of 6 trials and 624 patients, found that low-dose folic or folinic acid reduced gastrointestinal side effects by 26% in relative terms, transaminase elevation by 76.9% in relative terms, and treatment discontinuation — without reducing efficacy. That is the right example of “a supplement with methotrexate”: a supplement tested in randomized trials on people who take the drug, and one the rheumatologist prescribes personally.

What was measured alongside methotrexate — in mice and cells. 3 studies, and none of them asked your question. In 2011, an oral reishi polysaccharide (100–200 mg/kg) reversed in mice the damage that injected methotrexate caused to the lining of the small intestine, and the drop in serum IgA — a model of gut toxicity from chemotherapy, not of RA. In 2003, a water extract of cordyceps given together with methotrexate to mice with metastatic melanoma: body weight did not fall the way it did with methotrexate alone, and survival was longer — 6–7 mice per group. And in 2018, in a test tube, the culture fluid of cordyceps mycelium restored the proliferation of mouse spleen cells that methotrexate had suppressed — more on that in the chapter “Mushrooms boost the immune system”. All three are co-administration; none measured drug levels in blood, and none was in a patient.

The liver, and alcohol. In 2017, an observational study of 11,839 RA patients in the UK who started methotrexate found 530 episodes of liver enzymes rising threefold or more; above 21 units of alcohol a week — HR 1.85, and below 14 units — no association was found. A British unit is 8 grams of ethanol, so 14 units are 112 grams a week. Our extract contains 32% alcohol; a daily serving of about 1.4 ml provides about 0.35 grams of ethanol — arithmetic on the spec, not a measurement. We write it because anyone told to limit alcohol on methotrexate should know about it, and decide with the doctor.

And the mushrooms and the liver. Reishi has two reports worth knowing: in 2023, a 47-year-old man developed acute hepatitis after reishi powder taken with alcohol, and recovered within two weeks; in 2007, two patients were described — a Hong Kong case from 2004 and a Thai case from 2005 — both of whom were also taking other therapeutic agents, and in whom liver injury appeared one to two months after switching from boiled reishi to powder; one of them died of fulminant hepatitis. The NIH’s LiverTox database grades reishi D — a “possible rare cause” of liver injury; cordyceps and lion’s mane — E. None of this is evidence that the combination with methotrexate is dangerous — the combination simply was not measured. But anyone whose liver enzymes are checked every few months needs the doctor to know about anything new, so that a rise is not blamed on the wrong cause. We expanded on this on the mushrooms and the liver page.

And with Humira, Enbrel, Xeljanz or Olumiant?

0 studies that we found with our four mushrooms — for TNF blockers, rituximab, IL-6 blockers and JAK inhibitors. The difference between them lies in the theoretical axis: biologic drugs are proteins, broken down differently from chemical drugs, so an interaction through liver enzymes is less expected; Xeljanz is broken down mainly by the enzyme CYP3A4 — which reishi inhibited in rat liver. In humans — not measured.

Humira and Enbrel. Adalimumab and etanercept are proteins given by injection. The pathway through which a supplement changes a drug’s blood level — liver enzymes — is barely relevant to them. But “less expected” is not “tested”: there is not a single study. And the real question here is not pharmacokinetic but immunological — covered in the next chapter.

Xeljanz and Olumiant. Here there is a number, so it is worth knowing. In 2014 Pfizer, the maker of tofacitinib (Xeljanz), published two trials in 12 healthy volunteers each: ketoconazole — a strong CYP3A4 inhibitor — raised the area under the curve of tofacitinib by 103%, and fluconazole by 79%; the authors wrote that the combination “may require dose adjustment or restriction”. That is the bar for “interaction”. What exists on reishi: in 2007, a reishi polysaccharide inhibited, dose-dependently, CYP3A, CYP1A2 and CYP2E1 — in rat liver microsomes. A test-tube concentration cannot be compared with what reaches the blood when a supplement is swallowed — that was not measured — and MSKCC states explicitly that the clinical relevance “is not known”. There is no clinical human CYP study for any of the four mushrooms.

The wording we can stand behind: reishi inhibited, in rat liver, the enzyme family that breaks down Xeljanz; in humans this was not tested — so it is a question for the pharmacist. Not “reishi raises Xeljanz levels”, not “dangerous to combine”, not “safe to combine”. The full list of what was and was not measured is on the drug interactions page.

“Mushrooms boost the immune system” — what does that mean when your drug suppresses it?

It is a real question that was tested once — in mouse spleen cells, in a test tube. In healthy adults, beta-glucan from reishi raised CD3, CD4, CD8 and NK cells versus placebo; in cancer patients the rise was between 2.02% and 3.91%. RA drugs restrain that same system. What happens when the two directions meet in an RA patient — not measured. That is not evidence of danger, and it is not evidence of safety.

What the market claims. “Mushrooms don’t boost — they balance, so they are safe for autoimmune disease”. The claim sounds reassuring, but it does not rest on a measurement: the 2023 randomized trial in healthy adults — of purified beta-glucan from reishi, not of the mushroom extract — found an increase in CD3, CD4, CD8, the CD4/CD8 ratio and NK cells, and a significant difference in IgA and in NK-cell cytotoxicity whose direction the abstract does not state — one direction in everything that was reported. In the Cochrane review of cancer patients: CD3 rose by 3.91%, CD4 by 3.05% and CD8 by 2.02%, from studies whose quality was described as “generally insufficient”. On the language itself — “modulation” versus “boosting” — we wrote in reishi and the immune system: modulating or boosting?

The only direct test we found — in a test tube. In 2018 exactly this meeting was tested, in a dish: the culture fluid of cordyceps mycelium (not fruiting body) was added to mouse spleen cells that methotrexate had suppressed — and cell proliferation came back, and so did the secretion of IL-2, IFN-γ and TNF-α. In other words, in the dish, the mushroom worked against the direction of the drug. Some of the authors are employed by a Korean pharmaceutical company, and the animal part of the same study was done with cyclophosphamide, not methotrexate. What that means for an RA patient taking both — not measured, and from a dish one can conclude neither “dangerous” nor “safe”.

Why it does not carry over automatically to an RA patient. A rise of a few percent in a cell count in a healthy person is not a flare, and it says nothing about what happens when methotrexate or adalimumab is working in the background. And in RA patients themselves, in the only trial, not one immune marker moved — in either direction. What can be known today. We searched specifically for a report of an autoimmune flare after reishi, lion’s mane, cordyceps or turkey tail — and found none. What does exist is a 2004 series of three patients who flared — pemphigus and dermatomyositis — around the time they took echinacea and spirulina, other immune-stimulating supplements. And even the absence of reports on mushrooms is limited: adverse-event reporting for supplements is partial and far looser than for drugs, and a rheumatologist whose patient flares will usually not suspect a supplement. What to ask the doctor. “My drug restrains my immune system — is there a reason to avoid something that was measured as raising immune markers?”

“Beta-glucan worsens arthritis” or “reishi calms it” — what exactly was seen in mice?

Both, in different models. Molecules from reishi — ganoderic acid A and spore powder — eased collagen-induced arthritis in mice. And in genetically susceptible mice, a single injection of other beta-glucans — from yeast, from seaweed, from a bacterium and from a mushroom that is not ours — set off chronic arthritis. None of the models is a human, and none of them is swallowing an extract.

The “protective” side. In 2025, ganoderic acid A — a molecule isolated from reishi — was given at 20 or 40 mg/kg to 40 mice with induced arthritis; at the higher dose the arthritis score fell, and so did blood IL-6 and TNF-α. The same year, reishi spore powder taken by mouth eased joint destruction and pain hypersensitivity in mice, through an effect on neutrophils. And in cells from 12 RA patients, cordycepin — a molecule isolated from cordyceps — inhibited cartilage-degrading enzymes, in a test tube. That is what the sales pages quote.

The other side. In 2005, in SKG mice — mice with a spontaneous mutation that serve as an RA model — a single injection into the abdominal cavity of zymosan, curdlan or laminarin set off severe chronic arthritis; in ordinary mice — only a transient one; blocking the Dectin-1 receptor prevented it. The same year, the same Japanese group injected DBA/1 mice with Candida beta-glucan as an adjuvant to collagen — and got more severe arthritis than with complete Freund’s adjuvant; the authors wrote that fungal metabolites such as beta-glucans “are able to induce and aggravate autoimmune diseases such as RA”. In 2007, in SKG mice, beta-glucan from Candida and schizophyllan — a beta-glucan from another mushroom, a registered drug in Japan — caused more severe arthritis than laminarin; there the conclusion was more cautious: “fungal infection may be a factor” in the induction and aggravation of diseases such as RA. A 2018 study added the same direction.

Why none of them carries over to a person. The protective side was tested on isolated molecules and in induced models; the worsening side — by injection, which bypasses the gut and the liver, in mice built to fall ill, and not on even one of our four mushrooms. The conclusion we can stand behind: the molecule is not “gentle” by nature, and the outcome depends on genetics, route of administration and dose. What can be known today: that in real RA patients, taking it by mouth, the only thing measured showed no inflammatory effect in either direction. On the broader inflammatory mechanism — see does reishi affect the inflammatory response?

And with Plaquenil, prednisone or anti-inflammatories — does reishi “thin the blood”?

Plaquenil and prednisone — 0 interaction studies with our four mushrooms. On anti-inflammatories and bleeding there are two contradictory human studies: in an uncontrolled trial from 1990, 3 grams of reishi a day inhibited platelet aggregation by up to 31.49 percent; in a randomized trial from 2005, 1.5 grams a day did not change a single clotting measure. Both are true — and neither is the answer.

Plaquenil and prednisone. A search for mushroom polysaccharides with hydroxychloroquine returns 0 results. Prednisone appeared as background therapy in both arms of transplant trials with cordyceps, so nothing can be inferred from it about an interaction. “Not tested” — not “safe” and not “dangerous”.

Anti-inflammatories and bleeding. Many RA patients take an NSAID, so the question “does reishi increase bleeding” is relevant. The 1990 study: 33 patients with atherosclerotic disease, 1 gram three times a day, two weeks (plus 15 healthy volunteers whose blood was tested in vitro only) — maximal aggregation inhibition of 31.49 percent, and in-vitro thrombus length shortened from 30.05 to 20.4 mm; no control group. The 2005 study: 40 healthy volunteers, half of them on 1.5 grams of reishi a day for 4 weeks — no difference in clotting, fibrinogen, PFA-100 or thromboelastography; the authors wrote that use “is not expected to increase the risk of surgical bleeding in healthy people”. The differences: double the dose, patients versus healthy people, platelet aggregation versus overall clotting, and no control versus a randomized trial. What to do with this: before surgery or on an anticoagulant — tell the surgeon and the doctor about every supplement.

What was measured on the pain and fatigue you live with?

Not in RA patients. Fatigue fell by 28.3% from baseline on reishi — and by 20.1% on placebo — in 132 neurasthenia patients. In fibromyalgia, 6 grams of reishi a day improved endurance and flexibility — against carob flour, not placebo, and pain was not the endpoint. And on reishi and sleep there is not a single randomized human trial.

Fatigue is one of the hardest complaints in RA, and one of the least understood: a 2023 review of 134 reviews on fatigue in rheumatic diseases found that it has no agreed definition, that its 25 measurement instruments are all self-reported, and that non-drug interventions achieved a “negligible to small” effect. That is the background against which the reishi data should be read. Fatigue. The large trial, from 2005: 1,800 mg three times a day, 8 weeks; the sense of fatigue fell by 28.3% versus 20.1% on placebo, and 51.6% versus 24.6% improved “more than minimally”. The net difference is about 8 percentage points, in neurasthenia — a condition that is not autoimmune. A 2012 pilot in 48 breast cancer patients found an improvement on the fatigue scale after 4 weeks of spore powder. Pain. In the RA trial pain improved against baseline, in the group that also received San Miao San. In fibromyalgia, 64 women, 6 weeks: aerobic endurance, flexibility and speed improved — against carob flour, which is a comparator and not an inert placebo; pain was not measured as an outcome. On chronic pain in general we wrote on the chronic pain page, and on fibromyalgia — on the fibromyalgia page.

And sleep. “Reishi for sleep” is the most common Google completion for “reishi for…” in Hebrew — six out of fifteen. And there is not a single randomized human trial that has tested reishi and sleep; the dedicated search returns one record, and it is the fibromyalgia fitness study. We laid it out on the reishi for sleep page. What to ask the doctor. Fatigue in RA can come from disease activity, anemia, drugs or depression — each of which is checked differently. That is the place to start, before any supplement.

Can reishi actually make symptoms worse?

It was measured once, in a different population: in 29 men with Gulf War illness — a condition of chronic fatigue, pain and a neuroinflammatory component — at the high dose of reishi symptom severity was higher than on placebo (p=0.012); at the low dose — no change. That is not rheumatoid arthritis and not an autoimmune flare. It is the only trial we found in which symptom severity was higher on reishi than on placebo.

What exactly was measured. A 2021 pseudo-randomized crossover trial: each participant went through 30 days of baseline, 30 days of placebo, 30 days of low dose and 30 days of high dose, for three botanicals — reishi, stinging nettle and epimedium. At the low dose reishi did not differ from placebo (p=0.603); at the high dose severity was higher than on placebo. The authors: “reishi may exacerbate symptoms in some sufferers”, and alongside that — “small sample, preliminary results”. High-dose nettle, for comparison, reduced symptoms (p=0.048).

Why it is relevant, and why it is not. Gulf War illness is not RA, and it involves no inflamed joint. What they share is the experience — persistent fatigue, pain, and an involved immune system — in other words, outside the RA trial itself, the human population closest to an RA patient in which reishi was measured against placebo over time. And what it teaches: “natural” does not point in one direction, and dose matters. What can be known: anyone who starts a supplement and feels worse — fatigue, pain, swelling — stops, writes it down, and tells the rheumatologist. That data point of yours is worth more than any average.

What was actually measured in “natural treatment” for RA — that we do not sell?

Omega-3 and diet. In 22 trials in RA patients, fish oil reduced pain by an SMD of −0.21 — a small effect, with “moderate” quality of evidence; a later meta-analysis of 23 trials found −0.16, not significant. On diet, a Cochrane review of 14 randomized trials plus one controlled trial, 837 patients, concluded: “still uncertain”. We sell none of them.

“Arthritis natural treatment” and “rheumatoid arthritis diet” are what people search for, so it is worth knowing what was actually tested. Omega-3. A 2017 meta-analysis of 42 trials of marine oils in arthritis: in RA, 22 trials, a small reduction in pain (SMD −0.21); in OA — not significant. A 2012 meta-analysis of 10 trials, 183 patients versus 187 on placebo, at a dose of at least 2.7 grams a day for at least 3 months: anti-inflammatory drug use fell (p=0.011), but tender joints, swollen joints and morning stiffness — not significant. And a meta-analysis of 23 placebo-controlled trials, published in 2024, found pain −0.16, not significant, CRP down by only 0.21 mg/dl, certainty “low to very low”, and suggested that the drop in anti-inflammatory use in earlier studies may have stemmed from inadequate blinding. Diet. A 2009 Cochrane review: fasting followed by 13 months of vegetarian diet — pain fell by 1.89 on a 0–10 scale, in a single trial; a Cretan Mediterranean diet for 12 weeks — a reduction of 14.00 on a 0–100 scale, in a single trial; function and stiffness — no change; and in the diet groups dropout was 10% higher and weight fell by 3.23 kg. Psychological therapy. A 2020 Cochrane review of 75 studies and 9,401 participants — most with fibromyalgia, back pain or RA — found that CBT versus usual care reduced pain (SMD −0.22) and distress (−0.34): “a small or very small effect”, but a measured one.

Why this chapter is here: because this is what evidence on “natural treatment” looks like when it is measured — dozens of trials, small effects, disagreement. Our four mushrooms do not have even that. And choosing a supplement of this kind, if at all, belongs with the rheumatologist and the dietitian.

Rheumatoid, osteoarthritis, gout or psoriatic — why does the distinction matter when reading the studies?

Because each is a different disease, with a different research model. The only human trial of one of our four mushrooms was in RA. In osteoarthritis (OA) there is a molecule from reishi in mice and in cartilage cells only. In psoriatic arthritis a mushroom search returns 0 results. And gout is a metabolic disease of uric acid. Anyone who cites a study on one as proof for another is mixing them up.

In OA, the closest record is from 2022: ganoderic acid A in mice with an induced knee injury lowered cartilage-damage scores, alongside a test in human cartilage cells in culture. That is what there is. In psoriatic arthritis — the disease that links skin and joints — a dedicated search of the four mushrooms returns 0 results; on psoriasis itself and its biologic drugs we wrote on the psoriasis page. Gout is joint inflammation caused by uric acid crystals, not by an immune system attacking itself, and what was tested on it is entirely different — on the mushrooms and gout page. And when you read “mushrooms for arthritis” on any website — first ask which one.

What we actually measure in our bottle

After a page that says “not measured” in almost every row, you deserve to know what was measured — and about what exactly. We grow the mushrooms ourselves, on a farm in the Galilee: fresh fruiting body, not mycelium grown on grain and not imported powder whose history cannot be known. The mushroom goes from harvest straight to extraction, with no drying step in between; as far as we know, we are among the few in the world who work this way. The extraction is triple, and its alcohol stage runs for 7 weeks. The extraction ratio of the reishi is 1:3, and of the cordyceps 1:2.5, on a fresh-mushroom basis. Alcohol in the finished extract: 32% — the figure we wrote about in the methotrexate chapter, and one worth bringing to the rheumatologist together with your list of drugs.

And the numbers are not ours to set. We sent the finished extracts for testing at TÜV Austria, and what came back is the beta-glucan percentage on a dry-matter basis — and alongside it alpha-glucan, meaning starch, which was not detected in any of them. Alpha-glucan not detected is the chemical proof that there is no grain in the bottle. To understand why that matters, it helps to know the market’s three-step ladder: mycelium grown on grain, where beta-glucan is usually below 7% and most of the weight is starch; imported dried fruiting body, whose quality depends on who dried it and when; and fresh fruiting body from the farm, which is what we do. On a page that has dealt so much with beta-glucan and the immune system, it should also be said: this number describes what is in the bottle, not what it does in the body. Why beta-glucan and not “total polysaccharides” — we explained separately.

All our tests are public, and anyone who wants to read the report themselves will find our explanation of how to read a COA. Kosher certification — Mateh Yehuda Rabbinate, Rabbi Gad Atias. That is what we know how to measure and prove about what is in the bottle. What it will do for rheumatoid arthritis was not measured — so it is not written.

What this page does not say — and what we do not claim

We do not claim that reishi, cordyceps, lion’s mane or turkey tail improve rheumatoid arthritis, ease joint pain, reduce inflammation or “balance the immune system” — the only trial missed its primary endpoint, and the rest of the evidence is rodents and cells. Nor do we claim the opposite — that the mushrooms worsen RA: the worsening studies were done by injecting other beta-glucans into mice, and the Gulf War illness trial is a different population. We do not claim that the combination with methotrexate, Humira, Enbrel, Xeljanz, Olumiant, Plaquenil or prednisone is safe — it was not measured in humans; nor that it is dangerous — that was not measured either. We do not claim that omega-3 or diet are “proven” — the effects are small and the studies contradict each other, and we do not sell them. And we do not deal here with disability benefits, disability ratings or entitlements — we have no expertise in those and no sources on them. What we do say: rheumatoid arthritis is treated by a rheumatologist, and its drugs prevent irreversible damage. Do not stop, reduce or change them on your own, and anyone adding any supplement — including ours — tells the doctor before, not after. Under DSHEA, a dietary supplement may not claim to diagnose, treat, cure or prevent any disease. We sell mushroom extracts, and we are telling you explicitly not to buy them for arthritis.

The bottom line

Rheumatoid arthritis is the only autoimmune disease in which one of the four mushrooms we grow has been tested in a randomized human trial — reishi together with a herbal formula, 65 patients, half a year — and the trial missed its primary endpoint, with no change in plasma inflammatory or immune markers. With methotrexate, the biologic drugs, JAK inhibitors, Plaquenil and prednisone — no combination has been measured in humans; with methotrexate there are 3 studies in mice and cells, and what is known in humans concerns the liver, alcohol, and the enzyme that breaks down Xeljanz. On fatigue and pain there are data — in other populations, with a placebo that did almost the same. And there is one trial, in a different population, in which at a high dose symptom severity was higher on reishi than on placebo. If someone sells you a mushroom “for arthritis” — send them this page, and talk to your rheumatologist.

Frequently asked questions

Does reishi help with rheumatoid arthritis?

It was tested once in humans: 65 patients, 4 grams of reishi and 2.4 grams of San Miao San a day, 24 weeks, on top of their usual drugs. The primary endpoint, ACR20, was reached by 15% versus 9.1% on placebo — not significant. Immune and inflammatory markers did not change. Pain and self-assessment improved only as a secondary measure, against baseline.

Can I take medicinal mushrooms with methotrexate?

In humans the combination has not been tested — 0 interaction studies; in mice and cells there are 3 co-administration studies, none in a patient. Methotrexate requires monitoring of liver enzymes; reishi has two reports of liver injury, and our extract contains 32% alcohol — about 0.35 grams in a daily serving, by arithmetic on the spec. These are data for the rheumatologist, not a decision to make alone. The supplement that was tested with methotrexate is folic acid — and the doctor prescribes it.

And what about Humira or Enbrel?

0 studies with our four mushrooms. They are protein drugs, broken down differently from chemical drugs, so an interaction through liver enzymes is less expected — but “less expected” is not “tested”. The open question is immunological: purified beta-glucan from reishi raised immune-cell counts in healthy adults, and the drug restrains them. What happens when the two meet — not measured.

And what about Xeljanz or Olumiant?

Not measured. Xeljanz is broken down mainly by the enzyme CYP3A4, and a drug that strongly inhibits it — ketoconazole — raised its level by 103% in volunteers. Reishi inhibited CYP3A in rat liver microsomes; in humans that has never been tested. A question for the pharmacist, with the name of the drug and the name of the supplement in hand.

Mushrooms “boost immunity” — is that dangerous in an autoimmune disease?

Unknown. In healthy adults, beta-glucan from reishi raised CD3, CD4, CD8 and NK cells versus placebo; in RA patients, in the only trial, not one marker moved. No report of an autoimmune flare from the four mushrooms was found — but adverse-event reporting for supplements is partial and far looser than for drugs. “Not measured” is neither “safe” nor “dangerous”.

Can reishi help with fatigue in RA?

In RA patients — not measured. In neurasthenia, 132 patients, fatigue fell by 28.3% on reishi versus 20.1% on placebo — a difference of about 8 points. And in Gulf War illness, at a high dose symptom severity was higher on reishi than on placebo; at a low dose — no change. Fatigue in RA deserves a work-up with the doctor before any supplement.

Which natural treatment was actually tested in rheumatoid arthritis?

Omega-3 — in 22 trials, a small reduction in pain, and not significant in a later meta-analysis; vegetarian or Mediterranean diet — single trials with less pain, and Cochrane concludes “still uncertain”; CBT — a small but measured effect. We sell none of them, and the choice belongs with the rheumatologist.

Reishi thins the blood — can I take it with anti-inflammatories?

Two contradictory studies. In an uncontrolled trial, 3 grams a day inhibited platelet aggregation by up to 31.49 percent; in a randomized trial, 1.5 grams a day did not change a single clotting measure in 40 healthy volunteers. The differences: dose, population and measure. Before surgery, or on an anticoagulant — tell your doctor about every supplement.

Scientific sources (peer-reviewed)

• The only randomized trial: 65 RA patients (32/33), reishi 4 grams + San Miao San 2.4 grams a day on top of DMARDs, 24 weeks, 89% completed: ACR20 15% versus 9.1% (P>0.05); immune cells and cytokines unchanged; pain and global assessment — improvement in the herbal group only; 22 mild adverse events (8 versus 14) — Li EK, et al. Arthritis and Rheumatism, 2007. View on PubMed
• The same trial, immunological publication: CD4/CD8/NK/B, plasma IP-10, MCP-1, MIG, RANTES, IL-8, IL-18 — no difference at 8 and 24 weeks; only ex vivo induced IL-18 — Bao YX, et al. Immunopharmacology and Immunotoxicology, 2006. View on PubMed
• The same formula in rats with induced arthritis: injected — less allodynia, swelling and redness; swallowed — swelling and redness, not allodynia; on histology, by both routes — less cell infiltration and cartilage erosion — Lam FF, et al. Journal of Ethnopharmacology, 2008. View on PubMed
• Ganoderic acid A, 20 or 40 mg/kg, in 40 mice (including controls) with collagen-induced arthritis: arthritis score, IL-6 and TNF-α fell at the higher dose — Guzel Erdogan D, et al. Scientific Reports, 2025. View on PubMed
• Oral reishi spore powder in mice with collagen-induced arthritis: less joint destruction and pain hypersensitivity, through neutrophils — Huang S, et al. Frontiers in Immunology, 2025. View on PubMed
• Cordycepin inhibited MMP-1 and MMP-3 in synovial fibroblasts from 12 RA patients — in a test tube — Noh EM, et al. Rheumatology (Oxford), 2009. View on PubMed
• OA: ganoderic acid A in mice with induced knee injury and in human cartilage cells — damage scores and MMP-13 fell — Wu W, et al. Chemical Biology & Drug Design, 2022. View on PubMed
• SKG mice: a single intraperitoneal injection of zymosan, curdlan or laminarin set off severe chronic arthritis; Dectin-1 blockade prevented it — Yoshitomi H, et al. The Journal of Experimental Medicine, 2005. View on PubMed
• SKG mice: beta-glucan from Candida and schizophyllan — more severe arthritis than laminarin, high IL-6; “fungal infection may be a factor” — Hida S, et al. Biological & Pharmaceutical Bulletin, 2007. View on PubMed
• Candida beta-glucan as an adjuvant in DBA/1 mice — more severe arthritis than complete Freund’s adjuvant; fungal beta-glucans “are able to induce and aggravate autoimmune diseases such as RA” — Hida S, et al. Journal of Autoimmunity, 2005. View on PubMed
• Nod2-deficient SKG mice exposed to beta-glucan — aggravated arthritis, Th17 expansion — Napier RJ, et al. Journal of Immunology, 2018. View on PubMed
• Purified beta-glucan from reishi in healthy adults aged 18–55, 84 days, double-blind: increase in CD3, CD4, CD8, CD4/CD8 ratio and NK; a significant difference in IgA and NK cytotoxicity (direction not stated in the abstract) — Chen SN, et al. Foods, 2023. View on PubMed
• Cochrane, reishi in cancer patients: CD3 +3.91%, CD4 +3.05%, CD8 +2.02%; quality “generally insufficient” — Jin X, et al. Cochrane Database of Systematic Reviews, 2016. View on PubMed
• Three patients — pemphigus and dermatomyositis — who flared around the time of taking echinacea and spirulina (not mushrooms) — Lee AN, Werth VP. Archives of Dermatology, 2004. View on PubMed
• A reishi polysaccharide inhibited CYP2E1, CYP1A2 and CYP3A dose-dependently in rat liver microsomes — Wang X, et al. Biological & Pharmaceutical Bulletin, 2007. View on PubMed
• Tofacitinib (Xeljanz) — mainly CYP3A4; 12 volunteers per study: ketoconazole raised AUC by 103%, fluconazole by 79%. Pfizer — Gupta P, et al. Clinical Pharmacology in Drug Development, 2014. View on PubMed
• Cochrane, methotrexate versus placebo: 7 trials, 732; ACR50 — 15 more per 100; radiographic progression RR 0.31; withdrawal for side effects 16% versus 8% — Lopez-Olivo MA, et al. Cochrane Database of Systematic Reviews, 2014. View on PubMed
• Cochrane, folic/folinic acid with methotrexate: 6 trials, 624; transaminase elevation — 76.9% relative reduction; gastrointestinal effects — 26%; no loss of efficacy — Shea B, et al. Cochrane Database of Systematic Reviews, 2013. View on PubMed
• 11,839 RA patients on methotrexate: more than 21 units of alcohol a week — HR 1.85 for liver-enzyme elevation; under 14 — no association. Observational — Humphreys JH, et al. Annals of the Rheumatic Diseases, 2017. View on PubMed
• Mice: an oral reishi polysaccharide (100–200 mg/kg) reversed the small-intestinal mucosal damage and the drop in serum IgA caused by injected methotrexate; a gut-toxicity model, not RA — Chen LH, et al. Acta Pharmacologica Sinica, 2011. View on PubMed
• Mice with metastatic melanoma, 6–7 per group: a water extract of cordyceps together with methotrexate — without the weight loss methotrexate alone caused, and longer survival than controls; no interaction measured — Nakamura K, et al. Receptors & Channels, 2003. View on PubMed
• In a test tube: culture fluid of cordyceps mycelium restored the proliferation of mouse spleen cells suppressed by methotrexate, and the secretion of IL-2, IFN-γ and TNF-α; the animal part — with cyclophosphamide; some authors from a Korean pharmaceutical company — Shin JS, et al. Phytotherapy Research, 2018. View on PubMed
• A 47-year-old man, acute hepatitis after reishi powder with alcohol; recovery within two weeks — Guedikian R, et al. Cureus, 2023. View on PubMed
• Two patients (Hong Kong 2004, Thailand 2005), both also on other therapeutic agents: liver injury 1–2 months after switching from boiled reishi to powder; one — fatal fulminant hepatitis — Wanmuang H, et al. Journal of the Medical Association of Thailand, 2007. View on PubMed
• Reishi 3 grams a day, two weeks, 33 atherosclerotic patients, no control (plus 15 healthy donors — in vitro only): platelet aggregation inhibited by up to 31.49 percent; in-vitro thrombus 30.05 → 20.4 mm — Tao J, Feng KY. Journal of Tongji Medical University, 1990. View on PubMed
• Randomized trial, 40 healthy volunteers, reishi 1.5 grams a day for 4 weeks: zero change in clotting, fibrinogen, vWF, PFA-100, thromboelastography — Kwok Y, et al. Anesthesia and Analgesia, 2005. View on PubMed
• 29 men with Gulf War illness, pseudo-randomized crossover: low-dose reishi — like placebo (p=0.603); high dose — greater symptom severity (p=0.012). “Small sample, preliminary” — Younger J, et al. International Journal of Environmental Research and Public Health, 2021. View on PubMed
• 132 neurasthenia patients, 1,800 mg ×3 a day, 8 weeks: fatigue −28.3% versus −20.1% on placebo; “more than minimal improvement” 51.6% versus 24.6% — Tang W, et al. Journal of Medicinal Food, 2005. View on PubMed
• 64 women with fibromyalgia, 6 grams of reishi a day, 6 weeks, versus carob flour (not placebo): endurance, flexibility and speed improved; pain not an endpoint — Collado Mateo D, et al. Nutrición Hospitalaria, 2015. View on PubMed
• Pilot, 48 breast cancer patients on endocrine therapy, spore powder for 4 weeks: improvement on the fatigue scale — Zhao H, et al. Evidence-Based Complementary and Alternative Medicine, 2012. View on PubMed
• Cochrane, reishi for cardiovascular risk factors: risk of an adverse event RR 1.67 (0.86–3.24) — not significant, not serious — Klupp NL, et al. Cochrane Database of Systematic Reviews, 2015. View on PubMed
• A review of 134 reviews on fatigue in rheumatic diseases: no agreed definition; 25 measurement instruments, all self-reported; non-drug interventions — negligible to small effect — Beckers E, et al. RMD Open, 2023. View on PubMed
• Marine oils in arthritis, 42 trials: in RA (22) pain SMD −0.21, moderate quality; in OA — not significant — Senftleber NK, et al. Nutrients, 2017. View on PubMed
• Omega-3 in RA, 10 trials (183 versus 187), ≥2.7 grams a day for ≥3 months: NSAID use fell (p=0.011); joints and stiffness — not significant — Lee YH, et al. Archives of Medical Research, 2012. View on PubMed
• Omega-3 in RA, 23 placebo-controlled trials: pain −0.16, not significant; CRP −0.21 mg/dl; certainty low to very low — Gkiouras K, et al. Critical Reviews in Food Science and Nutrition, 2024. View on PubMed
• Cochrane, diet in RA: 14 randomized trials plus one controlled trial, 837 patients; vegetarian after fasting — pain −1.89 (0–10); Mediterranean — −14.00 (0–100); single trials; “still uncertain” — Hagen KB, et al. Cochrane Database of Systematic Reviews, 2009. View on PubMed
• Cochrane, psychological therapy for chronic pain: 75 studies, 9,401 participants; CBT versus usual care — pain −0.22, distress −0.34; “small or very small” — Williams ACC, et al. Cochrane Database of Systematic Reviews, 2020. View on PubMed

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This page is educational and does not constitute medical advice, diagnosis or a substitute for professional care. Medicinal mushroom extracts are dietary supplements, not drugs, and are not intended to treat rheumatoid arthritis or any other medical condition. Rheumatoid arthritis requires diagnosis and follow-up by a rheumatologist. Do not stop, replace or change the dose of methotrexate, a biologic drug, a JAK inhibitor, steroids or any other medication without your physician’s guidance. It describes what published trials and case reports recorded — and what was not recorded; it is not a prediction of what any individual will experience, and it is not a recommendation to start, stop or combine any supplement with any medication — those decisions belong with your physician, especially if you take regular medication, are pregnant or breastfeeding, have surgery planned, or have liver or kidney disease. *These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.*