Lupus, Natural Treatment and Supplements: What Was Measured, and What About Plaquenil

Lupus (systemic lupus erythematosus, SLE) is a systemic autoimmune disease, and anyone searching for a “natural treatment” for it mostly meets reishi (Ganoderma lucidum, the lingzhi of Chinese medicine) and cordyceps. The honest answer: none of our four mushrooms has been tested in people with lupus — only in mice. No study has tested a mushroom alongside hydroxychloroquine (Plaquenil) or prednisone. And in one of the two controlled trials of reishi in a fatigued population, the direction was reversed: at a high dose, symptom severity was higher than on placebo.

The kinds of evidence that do exist, from closest to a person to furthest away: on lupus itself — randomized trials of Plaquenil, meta-analyses on sleep, fatigue, exercise and vitamin D, and the 2023 EULAR recommendations; on the mushrooms and the immune system — trials in healthy people and in cancer patients in which immune markers rose; on the drugs — liver enzymes in a test tube, and trials in kidney transplant recipients in which cordyceps changed the dose of the immunosuppressant; and on lupus with a mushroom — two studies in mice and one molecule in a dish. This page sits at the crossroads: lupus, the drug, and the fatigue. We gathered the general picture of mushrooms and autoimmune disease on the medicinal mushrooms and autoimmune disease page.

Lupus and natural treatment — have medicinal mushrooms been tested in lupus?

Not in humans. We found not a single trial of reishi, cordyceps, lion’s mane or turkey tail in people with lupus. What exists: lupus mice given reishi with a Chinese herbal formula, mice given a different Ganoderma species, and an isolated cordyceps molecule tested on patients’ blood cells in a dish. That is a hypothesis in rodents — not evidence.

Across the whole autoimmune field, out of 13 diseases we screened, there is one randomized human trial with one of our four mushrooms — reishi in rheumatoid arthritis — and it missed its primary endpoint. In lupus there is not even that. So this page is not built around the question “does a mushroom help lupus”, whose answer is short, but around what you actually live with: Plaquenil you take for years, prednisone you are trying to taper, fatigue that does not lift, nights without sleep, and one question hovering over all of it — is a supplement that “boosts the immune system” even a good idea when the immune system is the problem?

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

The table sorts the questions you ask by what was measured on them and in which organism. The mushroom-in-lupus rows hold mice or nothing. The drug rows hold a test tube, or people who do not have lupus. And the only rows with trials in lupus patients themselves belong to things we do not sell: exercise and vitamin D.

Can you take medicinal mushrooms with Plaquenil?

Not measured — so it is a question for the pharmacist, with one fact in hand: hydroxychloroquine (Plaquenil) is broken down in the liver by three enzymes — CYP3A4, CYP2D6 and CYP2C8. Reishi inhibited CYP3A in rat liver microsomes. In humans the combination was never tested, either way. On cordyceps, lion’s mane and turkey tail versus these enzymes — no data.

Why this is the right question. Plaquenil is the anchor of lupus treatment, and the figure that explains why comes from a 1991 Canadian trial: 47 patients with stable lupus were randomized to continue the drug or switch to placebo for 24 weeks. In the placebo group 16 of 22 flared; in the group that continued — 9 of 25. A relative risk of 2.5, and the flare came sooner. At 42 months of follow-up, 50% of the placebo group versus 28% had a major flare — a difference that no longer reached significance, but the direction held. The 2023 EULAR recommendations set hydroxychloroquine for all lupus patients, at a target of 5 mg per kg of actual body weight a day.

Why the blood level matters in both directions. “Plaquenil eyes” is one of the top searches on the drug, and rightly so: among 2,361 patients who took it for at least 5 years, 7.5% developed retinal damage. At a dose of 4–5 mg/kg the prevalence stayed below 2% in the first ten years — and rose to almost 20% after 20 years; above 5 mg/kg the odds ratio was 5.67. From the other side, in an Italian study of 83 patients, those with higher blood levels of the drug flared less — and the blood level did not match the prescribed dose. In other words, the Plaquenil dose is calibrated between the eye and the flare, and whatever changes the blood level changes that balance.

What is known about the mushrooms and the enzymes. In 2023, in human liver microsomes, researchers in Helsinki found that CYP2D6 and CYP3A4 break down hydroxychloroquine in almost equal shares, and CYP2C8 to a smaller extent. In 2007, a reishi polysaccharide inhibited, in liver microsomes from rats (in a liver-injury model) and dose-dependently, CYP3A, CYP1A2 and CYP2E1; the authors write that drug pharmacokinetics “may be altered”. The cancer center MSKCC cites the same finding and adds: “the clinical relevance is unknown”. We found no study that tested one of our four mushrooms against CYP2D6 or CYP2C8, and none that measured Plaquenil blood levels in someone taking a mushroom.

The wording we can stand behind: reishi inhibited, in rat liver, an enzyme that takes part in breaking down Plaquenil; in humans that was not tested — so it is a question for the pharmacist, not a decision to make alone. Not “dangerous to combine”, not “safe to combine”. What to bring to the pharmacist: the name and dose of the drug, the name of the supplement, and the list of your other medications. The wider list — on the drug interactions page.

And with prednisone, or with tacrolimus in lupus nephritis?

Prednisone — not tested as an interaction with any of our four mushrooms. Cyclosporine and tacrolimus are the only pairing we found in which a mushroom and an immunosuppressive drug were measured together in humans with the drug dose reported: in kidney transplant recipients given cordyceps, the drug doses and blood levels were lower. That is not lupus — and in that measurement something changed; what caused the change was not measured.

Prednisone. “Plaquenil steroids” is one of Google’s top completions for the drug’s name. The 2023 EULAR recommendations define steroids as a “bridge” for active periods, and for maintenance — 5 mg a day or less, stopping when possible. A 2022 meta-analysis of 635 patients who stopped steroids found that taking Plaquenil at the same time tended to reduce flares (OR 0.50) — a trend that did not reach significance. On mushrooms: prednisone appeared as background therapy in both arms of the transplant trials with cordyceps, and nobody measured an interaction.

Tacrolimus and cyclosporine. In lupus nephritis, EULAR recommends considering the addition of calcineurin inhibitors — tacrolimus or voclosporin. And it is precisely on this family that there is human data. In a trial of 202 kidney transplant recipients, those given cordyceps 1 gram three times a day needed lower cyclosporine doses in months 2–6, and blood trough levels were lower in months 3–6. In a retrospective analysis of 67 transplant recipients (25 on a cordyceps mycelium preparation, 42 without), the cyclosporine or tacrolimus dose after 12 weeks was significantly lower in the cordyceps group. A Cochrane review of 5 studies and 447 participants rated the evidence “limited and of low quality”. In all of them cordyceps was given within a study and under close medical follow-up, and according to that review only one of them was designed around a deliberately low cyclosporine dose; what lowered the doses was not measured. Someone taking tacrolimus for lupus who adds cordyceps off the shelf has no such follow-up. What to ask: not “is cordyceps safe”, but “do I need a tacrolimus level check if I start a supplement”. On methotrexate, mycophenolate and biologics — 0 human interaction studies with our four mushrooms.

Mushrooms that “boost immunity” — why is this the most sensitive question in lupus?

Because in lupus the immune system is the problem and the drugs calm it, while reishi in humans was measured raising immune markers — not balancing them. A 2025 review listed reishi among the 15 herbs with the best-documented immunostimulatory properties. Yet we found not one report of a lupus flare from one of our four mushrooms. A data void — not an alarm, not reassurance.

What was measured. In 2023, a purified reishi beta-glucan — not a reishi extract — given to healthy adults for 84 days, in a double-blind trial, raised CD3, CD4 and CD8 cells, the CD4/CD8 ratio and NK cells; in IgA and NK cytotoxicity there was a significant difference whose direction the abstract does not state. A 2016 Cochrane meta-analysis found in cancer patients a rise of 3.91% in CD3, 3.05% in CD4 and 2.02% in CD8. One direction — up. We went into more depth on the medicinal mushrooms and the immune system page.

What the physicians wrote. In 2025 a group from the University of Pennsylvania published, in a lupus journal, a scoping review that screened 11,819 papers and found 227 herbs and supplements with immunostimulatory properties. 15 of them were supported by all three kinds of evidence — test tube, animal and human — among them alfalfa, echinacea, astragalus, spirulina, ginseng and reishi mushroom. The purpose of the list, in their words: to help physicians counsel patients with autoimmune skin diseases. It matters to read it correctly: this is a list of properties — receptor activation, inflammatory cytokines — not of flares observed after reishi. The same researcher described in 2004 three cases of autoimmune skin disease flaring in close proximity to echinacea and spirulina — not mushrooms.

What is not known. We searched explicitly for a case report of an autoimmune flare after reishi, cordyceps, lion’s mane or turkey tail — and found none. And that does not prove safety: reporting of side effects from supplements is largely voluntary, and a rheumatologist whose patient flared will usually not suspect a supplement. Whoever writes “mushrooms are dangerous in lupus” is making it up, and whoever writes “mushrooms balance the immune system and so suit lupus” is making it up too. What to ask the rheumatologist: in my situation — active or quiet disease, on which drugs — is there a reason to avoid any supplement that stimulates the immune system?

Is there a supplement already linked to lupus? This is what a real signal looks like

Yes — alfalfa. In 1982, monkeys fed alfalfa sprouts developed a lupus-like syndrome, and the amino acid L-canavanine they contain reactivated the syndrome. A volunteer who developed lupus-like autoimmunity while taking alfalfa seeds was also described. In humans taking alfalfa tablets the link remains “controversial”. For our four mushrooms we found not even a signal like that.

This chapter exists to give a sense of scale. When people talk about “a supplement that may worsen lupus”, this is what the strongest evidence there is looks like: a trial in macaque monkeys published in Science, in which the food triggered blood and antibody abnormalities resembling human lupus, and in which re-exposure to the single component triggered the disease again. A 2006 review sums it up: in susceptible lupus mice L-canavanine worsened the disease, in a normal mouse strain — it did not; in humans there are few reports, and they are controversial; epidemiological studies — almost none. Alfalfa also appears on the 2025 list of 15 herbs. Reishi is on the same list on the strength of mechanism studies — but without monkeys, without a volunteer who fell ill and without re-exposure. The difference between “an immunostimulatory property” and “a clinical signal” is exactly the difference between these two rows.

What happened when reishi was tested in a population with chronic fatigue?

At the high dose, symptom severity was higher than on placebo (p=0.012); at the low dose — no change (p=0.603). That was in 2021, in a placebo-controlled, pseudo-randomized crossover trial in 29 men with Gulf War illness. This is not lupus and not an “autoimmune flare” — but it is one of the two controlled trials in which reishi was measured on symptoms in a fatigued population, and here the direction was the opposite of the neurasthenia trial.

Gulf War illness is a multisystem condition of chronic fatigue, pain and a neuroinflammatory component in soldiers who served in that war. It is not an autoimmune disease. We bring it because the overlap in symptoms — persistent fatigue, pain, an inflammatory component — is exactly what lupus patients describe, and because apart from the arthritis trial discussed below we found no closer study. The design: 30 days of baseline, 30 days of placebo, 30 days of low dose and 30 days of high dose. The authors’ conclusion, word for word: “reishi may exaggerate symptoms in some GWI sufferers”. And in the same breath: the results come from a small sample and are preliminary.

What this does not say: that reishi worsens lupus — that was not tested. What it does say: that the sentence “at worst a mushroom simply won’t help” does not stand up to the data. Of the two controlled trials that measured symptoms in a fatigued population — neurasthenia in 2005 and Gulf War illness in 2021 — in the second the direction was reversed and dose-dependent. And in lupus, where it is hard to tell a flare from “a bad day”, this is worth remembering: if you started a supplement — any supplement — and felt worse, that is a data point you are measuring on yourself. Stop, and tell your doctor.

“Reishi lowered antibodies in lupus mice” — what exactly was measured?

In 2016, lupus mice given reishi together with the Chinese formula San Miao San — 7 days by mouth, then 7 days by injection into the abdominal cavity — showed a drop in anti-dsDNA antibodies and a rise in regulatory T and B cells. 10 mice per group. That is not reishi alone, not by mouth alone, and not a human.

What the market claims. “Reishi regulates the immune system in lupus”, “reishi lowers antibodies”. The sentence rests on two mouse studies and one molecule. What exactly was measured. The 2016 study from Hong Kong used female MRL/lpr mice, a strain that develops lupus on its own: 500 mg/kg a day by mouth, then 50 mg/kg by injection. Anti-dsDNA antibodies fell significantly in moderate and severe lupus, Treg cells rose in the spleen, thymus and blood and Breg cells in the spleen and thymus, and some cytokines fell. The 2001 study from Taiwan fed NZB/NZW mice an extract of Ganoderma tsugae — a different Ganoderma species, not the one in our bottle — from two months of age, alongside a prednisolone group; survival improved, and urine protein and antibodies fell. And in 2025, cordycepin — a molecule isolated from cordyceps mushrooms — suppressed type I interferon in blood cells from lupus patients in a dish and in genetically engineered mice.

Why it does not carry over automatically to a person. A two-ingredient formula does not let you know what worked; injection into the abdominal cavity bypasses the digestive system; 14 days in a mouse are not years of disease in a person; a different Ganoderma species is a different mushroom; and an isolated molecule in a dish is not a swallowed extract. What can be known today: that there is an interesting direction in rodents, and that nobody has tested it in a single patient. What to ask the doctor: not “does reishi lower antibodies”, but “which of my markers — antibodies, complement, urine — would show whether something is changing, and when are they checked”.

Fatigue in lupus — what was measured on it?

On mushrooms in lupus — nothing. On reishi for fatigue in other populations — one large randomized trial: 132 neurasthenia patients, fatigue fell 28.3% versus 20.1% on placebo; and one small randomized pilot in breast cancer. In lupus itself, what was measured is exercise: in a meta-analysis informing the EULAR recommendations — an SMD of −0.54; in a 2023 Cochrane review — low certainty. We sell neither.

Reishi. The largest and cleanest trial of reishi and fatigue, from 2005: 132 patients with neurasthenia, 1,800 mg of polysaccharide three times a day, 8 weeks, double-blind. The sense of fatigue fell by 28.3% — and on placebo by 20.1%. The real difference is about 8 percentage points, and whoever writes “28% less fatigue” is leaving out the placebo. 51.6% versus 24.6% were reported as “more than minimally improved”. In 2012, in a randomized pilot of 48 breast cancer patients on hormone therapy, reishi spore powder for 4 weeks improved the fatigue questionnaire — the nature of the control group is not specified in the abstract. None of these populations is lupus, and none of them takes Plaquenil.

What was measured in lupus patients. A systematic review of 82 randomized trials, 55 of them in the meta-analysis, that informed the 2023 EULAR fatigue recommendations found that exercise reduced fatigue in lupus — an SMD of −0.54, with a confidence interval that almost touches zero; psycho-educational interventions in lupus — did not reach significance. A Cochrane review from the same year, of 13 studies and 540 participants, is more cautious: against usual care, training had “little or no effect” on fatigue, and the comparison against relaxation showed perhaps a slight reduction — at low certainty. A 2017 meta-analysis of 11 studies and 469 participants added what matters to patients: training did not worsen disease activity. If the fatigue comes with widespread muscle pain — the fibromyalgia page may be relevant to you.

Reishi for sleep with lupus — is there any research on it?

No. There is not a single randomized human trial of reishi and sleep — in lupus or at all. A dedicated PubMed search returned one result: a fitness study in fibromyalgia. This is exactly where demand and the gap meet: 59.7% of adults with lupus have a sleep disorder, and “reishi for sleep” is the most common reishi search in Israel.

What the market claims. Six of Google’s fifteen Hebrew completions for “reishi for…” are about sleep: “before sleep”, “reishi drops for sleep”, “reishi extract for sleep”. The whole market sells reishi for sleep. What exactly was measured. In the 2005 fatigue trial, fatigue and well-being were measured — not sleep. And in the fibromyalgia fitness trial — fitness, against carob and not against placebo. What was measured on sleep in lupus. A 2021 meta-analysis of 18 studies — 1,086 lupus patients versus 2,866 controls — found that the Pittsburgh Sleep Quality Index was worse by 3.45 points in the patients, and the leading complaints were daytime dysfunction, subjective sleep quality and sleep efficiency. A 2024 meta-analysis of 203 studies found that sleep disorder is the most common mental health condition in lupus: 59.7%.

Why it does not carry over, and what can be known. There is nothing to carry over: there is not one randomized trial that measured reishi on sleep, not in lupus and not in any other population — and in the 2016 Cochrane review, insomnia actually appears on the list of mild side effects reported. And in that same 2021 meta-analysis, lupus patients with fibromyalgia did not sleep worse than lupus patients without it — meaning poor sleep is not explained by widespread pain alone, and it belongs in the conversation with the rheumatologist. What to ask: what is hurting my sleep — pain, mood, disease activity or one of the drugs — and what has been tested on each of these. Everything that was and was not tested on reishi and sleep is gathered on the reishi for sleep page.

What was measured in lupus that we do not sell — vitamin D?

Vitamin D was tested in randomized trials in lupus patients, and the results conflict. A 2019 meta-analysis of 5 trials and 490 participants: fatigue fell (in two trials, 79 participants), disease activity did not fall significantly. A 2025 meta-analysis of 21 studies and 3,177 participants: a one-point drop on the SLEDAI activity index. We do not sell vitamin D.

In Hebrew, “lupus diet” returns no completion, and “lupus natural treatment” returns lists of herbs. So it is worth knowing what was actually tested on a supplement in lupus patients themselves. The 2019 meta-analysis found that vitamin D raised its level in the blood and reduced fatigue (SMD −1.179) — but only in two trials — and did not significantly change the activity index (p=0.070) or anti-dsDNA antibodies; serious side effects — none reported. The 2025 meta-analysis, far broader, counted 12 positive studies and 9 with no effect, and in the pooled analysis found a one-point drop in SLEDAI versus placebo. Two meta-analyses, two answers — and neither of them includes a mushroom. We write these numbers because they are what was measured, not to recommend; the vitamin level is checked in the blood, and the dose is set by the doctor.

Lupus anticoagulant and blood thinners — what about reishi?

“Lupus anticoagulant” is not a drug — it is a marker of antiphospholipid syndrome (APS), which accompanies some people with lupus and may mean years on an anticoagulant. On reishi and platelets, two human studies contradict each other: up to 31.49% inhibition at 3 grams a day, and zero difference at 1.5 grams a day.

In 1990, 33 patients with atherosclerosis — not lupus — given reishi 3 grams a day for two weeks, with no control group, showed a maximum inhibition of 31.49% in ADP-induced platelet aggregation (at 2 micromol per liter). In 2005, a double-blind trial in 40 healthy volunteers, 1.5 grams a day for 4 weeks, found no difference on any clotting measure. Double the dose, patients versus healthy people, a different measure — and both studies are correct. On cordyceps there is one case report of increased bleeding after a tooth extraction. Anyone who has antiphospholipid syndrome alongside lupus and takes an anticoagulant or aspirin will find the full detail on the blood thinners and medicinal mushrooms page — including the difference between the two trials, number against number.

Joint pain in lupus — what about the one trial of one of our mushrooms in arthritis?

It is the only randomized trial of one of our mushrooms in any autoimmune disease: 65 rheumatoid arthritis patients, reishi 4 grams plus a herbal formula, 24 weeks. The primary endpoint — 15% versus 9.1% on placebo, not significant. Immune cells and cytokines did not move. That is not lupus, and the preparation was not reishi alone.

Joint pain is common in lupus, and so anyone searching for a “natural treatment” for the joints reaches this 2007 trial. What improved in it was the pain score and the patient’s own assessment — secondary outcomes — and in the same breath the authors wrote that no anti-inflammatory or immunomodulatory effect was demonstrated. If your lupus comes with arthritis, the full detail — including what was measured with methotrexate and with biologics — is on the rheumatoid arthritis and natural treatment page. And if the pain has become chronic and widespread, the chronic pain page lays out what was measured there. One thing concerns everyone: anyone taking methotrexate or mycophenolate is looking after their liver, and reishi has a case report of liver injury after powder taken with alcohol and a “possible rare cause” rating in the LiverTox database; in the 2015 Cochrane review of reishi taken for 4 months, the risk ratio for an adverse effect was 1.67 — not significant, and none serious. We laid it out on the medicinal mushrooms and the liver page.

What we actually measure in our bottle

After a whole page of “not measured”, 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 origin cannot be verified. 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. Extraction ratios on a fresh-mushroom basis: reishi 1:3 and cordyceps 1:2.5. Alcohol in the finished extract: 32% — a figure worth bringing to the pharmacist together with the name of your drug, especially if you take a drug that puts a load on the liver.

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. And on a page that talks about the immune system, it should also be said: beta-glucan is precisely the component that was measured raising immune markers in healthy people. We measure how much of it is in the bottle — not what it does in lupus. 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 lupus 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 lower antibodies, calm lupus, prevent flares or replace Plaquenil, prednisone or any other drug — none of them has been measured in people with lupus. We do not claim that they change Plaquenil blood levels — that was not measured; and we do not claim that they do not change them — that was not measured either. We do not claim they are dangerous in lupus, nor that they are safe in it. We do not claim that reishi eases fatigue or improves sleep in lupus — the fatigue trial was done in another population, and on sleep there is no randomized trial at all. We do not claim that vitamin D or exercise are “proven” in lupus — the data on them are mixed, and we do not sell them. And we do not deal here with disability benefits, disability ratings, pregnancy or cutaneous lupus — we have no expertise in those and no sources on them. What we do say: lupus is diagnosed and monitored by a rheumatologist; anyone taking Plaquenil, prednisone, tacrolimus or any immunosuppressant talks to the doctor or pharmacist before any supplement, including ours. 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 lupus.

The bottom line

Our four mushrooms have not been tested in people with lupus; what exists is mice — with a combined formula, with a different Ganoderma species — and one molecule in a dish. They have not been tested alongside Plaquenil or prednisone, and in kidney transplant recipients given cordyceps the cyclosporine and tacrolimus doses were lower — meaning that in at least one measured pairing, cordyceps and cyclosporine, the dose changed; on the other pairings there is no data. What was measured for reishi in humans is a rise in immune markers, and in another fatigued population, at a high dose of reishi, symptom severity was higher than on placebo. On sleep there is not one randomized trial. What was tested in lupus patients — exercise and vitamin D — gives modest, mixed results, and we do not sell those either. And if someone sells you a mushroom “to balance immunity in lupus” — send them this page, and go to a rheumatologist.

Frequently asked questions

Is there a natural treatment for lupus?

Lupus treatment rests on hydroxychloroquine for all patients, and on steroids and immunosuppressants as needed — and no supplement has been tested as a substitute. Our four mushrooms have not been tested in lupus patients at all — only in mice. What was tested in patients themselves is exercise and vitamin D, and there the results are modest and mixed.

Can I take reishi with Plaquenil?

Not tested — no study has tested a mushroom alongside hydroxychloroquine. It is known that the drug is broken down by the liver enzymes CYP3A4, CYP2D6 and CYP2C8, and that reishi inhibited CYP3A in a test tube, in rat liver. In humans — not measured. It is a question for the pharmacist, and especially for the rheumatologist who calibrates the dose by weight.

Why does Plaquenil harm the eyes, and what does that have to do with supplements?

Among 2,361 patients who took Plaquenil for at least 5 years, 7.5% developed retinal damage; at 4–5 mg/kg — under 2% in the first ten years and almost 20% after 20 years. The dose is calibrated between the eye and the flare, so anything that might change the drug’s blood level is a question for the doctor.

Mushrooms boost the immune system — isn’t that dangerous in lupus?

Unknown. In healthy people (a purified reishi beta-glucan) and in cancer patients (reishi), immune markers such as CD4, CD8 and NK cells rose, and a 2025 review listed reishi among the best-documented immunostimulatory herbs. On the other hand, we found not a single report of a lupus flare after one of our four mushrooms. It is a data void — a question for the rheumatologist, neither “safe” nor “dangerous”.

Does reishi help with lupus fatigue?

Not tested in lupus. In one trial of 132 neurasthenia patients, fatigue fell 28.3% versus 20.1% on placebo — a different population. And in a trial of 29 men with Gulf War illness, a chronic fatigue condition, high-dose reishi was actually associated with more severe symptoms. In lupus itself, exercise was measured, at low to moderate certainty.

Reishi for sleep with lupus — does it work?

There is not a single randomized human trial on it, not in lupus and not at all. Poor sleep is very common in lupus — a sleep disorder in 59.7% of adults — and it is worse on average by 3.45 points on the Pittsburgh index than in people without lupus. The causes are checked with the doctor, not with an extract.

I’m on prednisone — what about medicinal mushrooms?

Not tested as an interaction. Prednisone appeared as background therapy in transplant trials with cordyceps, without any measurement of the combination. What was measured: in kidney transplant recipients given cordyceps, the cyclosporine and tacrolimus doses were lower — with no mechanism measured — so anyone taking an additional immunosuppressive drug for lupus should ask the doctor before any supplement.

Are there supplements known to worsen lupus?

The best-documented example is alfalfa: monkeys fed alfalfa sprouts developed a lupus-like syndrome, and its component L-canavanine reactivated it. In humans the link is controversial. A 2025 review listed 15 herbs with the best-documented immunostimulatory properties, among them echinacea, spirulina and reishi — a list of properties, not of observed flares.

Scientific sources (peer-reviewed)

• 47 patients with stable lupus, randomized double-blind, 24 weeks: stopping hydroxychloroquine — a flare in 16 of 22 versus 9 of 25 who continued; relative risk 2.5; severe exacerbation 5 of 22 versus 1 of 25 — Canadian Hydroxychloroquine Study Group. The New England Journal of Medicine, 1991. View on PubMed
• The same 47 patients, 42 months: major flare in 50% on placebo versus 28%; relative risk 0.43 — not significant — Tsakonas E, et al. Lupus, 1998. View on PubMed
• 83 patients, 24 months: higher hydroxychloroquine blood levels — fewer flares; the blood level did not match the prescribed dose — Fasano S, et al. Lupus Science & Medicine, 2023. View on PubMed
• Human liver microsomes: hydroxychloroquine is broken down by CYP3A4, CYP2D6 and CYP2C8, and inhibits CYP2D6. Test tube — Paludetto MN, et al. Drug Metabolism and Disposition, 2023. View on PubMed
• 2,361 patients on hydroxychloroquine for at least 5 years: retinopathy 7.5%; above 5 mg/kg — OR 5.67; at 4–5 mg/kg — under 2% at 10 years, almost 20% after 20 years — Melles RB, Marmor MF. JAMA Ophthalmology, 2014. View on PubMed
• EULAR recommendations for lupus, 2023 update: hydroxychloroquine for all patients at a target of 5 mg/kg; maintenance steroids — 5 mg a day or less; calcineurin inhibitors in lupus nephritis — Fanouriakis A, et al. Annals of the Rheumatic Diseases, 2024. View on PubMed
• Meta-analysis, 635 patients who stopped steroids: concurrent hydroxychloroquine — OR 0.50 for a flare, a non-significant trend — Ji L, et al. Lupus Science & Medicine, 2022. View on PubMed
• A reishi polysaccharide dose-dependently inhibited CYP3A, CYP1A2 and CYP2E1 in rat liver microsomes — not in humans — Wang X, et al. Biological & Pharmaceutical Bulletin, 2007. View on PubMed
• 202 kidney transplant recipients, open-label trial, cordyceps 1 gram ×3 a day: lower cyclosporine doses in months 2–6 and lower trough levels in months 3–6; mechanism not measured. Not lupus — Li Y, et al. Transplantation Proceedings, 2009. View on PubMed
• Retrospective analysis, 67 kidney transplant recipients (25 on a cordyceps mycelium preparation, 42 without): cyclosporine or tacrolimus dose at 12 weeks lower in the preparation group. Not a trial, not lupus — Ding CG, et al. Chinese Journal of Integrated Traditional and Western Medicine, 2009. View on PubMed
• Cochrane, cordyceps in kidney transplant recipients: 5 studies, 447 participants; “limited, low-quality evidence” — Hong T, et al. Cochrane Database of Systematic Reviews, 2015. View on PubMed
• MRL/lpr lupus mice, reishi + San Miao San, 7 days by mouth and 7 by injection, 10 mice per group: anti-dsDNA fell, Treg and Breg rose. Rodents only — Cai Z, et al. Chinese Medicine, 2016. View on PubMed
• NZB/NZW lupus mice, an extract of Ganoderma tsugae — a different species: survival rose, urine protein and antibodies fell. Rodents only — Lai NS, et al. Lupus, 2001. View on PubMed
• Isolated cordycepin suppressed type I interferon in blood cells from lupus patients in a dish and in engineered mice. Not an extract, not a clinical trial — Yang D, et al. British Journal of Pharmacology, 2025. View on PubMed
• Purified reishi beta-glucan (not an extract), healthy adults, 84 days, double-blind: a rise in CD3, CD4, CD8, the CD4/CD8 ratio and NK cells; a significant difference in IgA and NK cytotoxicity — direction not stated — Chen SN, et al. Foods, 2023. View on PubMed
• Cochrane, reishi in cancer patients: CD3 +3.91%, CD4 +3.05%, CD8 +2.02%; study quality “not sufficient” — Jin X, et al. Cochrane Database of Systematic Reviews, 2016. View on PubMed
• Scoping review: 11,819 papers, 227 herbs with immunostimulatory properties; 15 with the strongest evidence, among them reishi, alfalfa, echinacea and spirulina — a list of properties, not of flares — Weiner JD, et al. Lupus Science & Medicine, 2025. View on PubMed
• 3 cases of autoimmune skin disease flaring in proximity to echinacea and spirulina — not mushrooms — Lee AN, Werth VP. Archives of Dermatology, 2004. View on PubMed
• Macaque monkeys fed alfalfa sprouts developed a lupus-like syndrome; L-canavanine reactivated it — Malinow MR, et al. Science, 1982. View on PubMed
• L-canavanine and autoimmunity — a review: the link in humans is “controversial”; epidemiological studies sparse — Akaogi J, et al. Autoimmunity Reviews, 2006. View on PubMed
• 29 men with Gulf War illness, placebo-controlled, pseudo-randomized crossover: low-dose reishi — no change (p=0.603); high dose — higher 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, reishi polysaccharide for 8 weeks: fatigue −28.3% versus −20.1% on placebo. Not lupus — Tang W, et al. Journal of Medicinal Food, 2005. View on PubMed
• Randomized pilot, 48 breast cancer patients on hormone therapy: reishi spore powder for 4 weeks improved the fatigue questionnaire. Nature of the control group not specified in the abstract; not lupus — Zhao H, et al. Evidence-Based Complementary and Alternative Medicine, 2012. View on PubMed
• 64 women with fibromyalgia, reishi 6 grams a day for 6 weeks: improved fitness — against carob, not against placebo — Collado Mateo D, et al. Nutrición Hospitalaria, 2015. View on PubMed
• Informing the EULAR fatigue recommendations: 82 trials included, 55 in the meta-analysis; exercise in lupus SMD −0.54; psycho-educational intervention in lupus — not significant — Santos EJF, et al. RMD Open, 2023. View on PubMed
• Cochrane, exercise training in lupus: 13 studies, 540 participants; versus usual care — little or no effect on fatigue; low certainty — Frade S, et al. Cochrane Database of Systematic Reviews, 2023. View on PubMed
• 11 studies, 469 participants: training did not worsen lupus activity, and reduced fatigue and depression — O’Dwyer T, et al. Seminars in Arthritis and Rheumatism, 2017. View on PubMed
• Meta-analysis, 18 studies: 1,086 lupus patients versus 2,866 controls — Pittsburgh index worse by 3.45 points — Wu L, et al. Clinical Rheumatology, 2021. View on PubMed
• Meta-analysis, 5 studies: every component of sleep worse in women with lupus — Zhao Q, et al. Psychology, Health & Medicine, 2018. View on PubMed
• 203 studies: sleep disorder — the most common mental health condition in adults with lupus, 59.7% — Liu X, et al. Rheumatology (Oxford), 2024. View on PubMed
• Vitamin D in lupus, 5 trials, 490 participants: fatigue fell (2 trials); disease activity — not significant (p=0.070) — Zheng R, et al. The American Journal of the Medical Sciences, 2019. View on PubMed
• Vitamin D in lupus, 21 studies, 3,177 participants: 12 positive, 9 with no effect; SLEDAI fell by one point — El Kababi S, et al. Nutrients, 2025. View on PubMed
• Reishi 3 grams a day for two weeks, 33 atherosclerosis patients, no control: maximum inhibition of 31.49% in ADP-induced platelet aggregation (2 micromol per liter) — Tao J, Feng KY. Journal of Tongji Medical University, 1990. View on PubMed
• 40 healthy volunteers, reishi 1.5 grams a day for 4 weeks, double-blind: no difference on any clotting measure — Kwok Y, et al. Anesthesia and Analgesia, 2005. View on PubMed
• The only randomized trial of one of our mushrooms in an autoimmune disease: 65 rheumatoid arthritis patients, reishi + San Miao San, 24 weeks — 15% versus 9.1%, not significant — Li EK, et al. Arthritis and Rheumatism, 2007. View on PubMed
• Case report: a 47-year-old man, acute hepatitis after reishi powder with alcohol, full recovery within two weeks — Guedikian R, et al. Cureus, 2023. View on PubMed
• Cochrane, reishi for 4 months: a risk ratio of 1.67 for an adverse effect — not significant, not serious — Klupp NL, et al. Cochrane Database of Systematic Reviews, 2015. View on PubMed

Read next

• Medicinal mushrooms and autoimmune disease — the full picture
• Blood thinners and supplements — medicinal mushrooms and platelets
• Rheumatoid arthritis and natural treatment
• Fibromyalgia and supplements
• Chronic pain and medicinal mushrooms
• Medicinal mushrooms and the liver
• Reishi for sleep — what was measured and what was not
• Reishi and the immune system: modulation or boosting?
• How mushrooms modulate the immune system
• Drug interactions
• Do medicinal mushrooms have side effects?
• Who shouldn’t take reishi
• Who shouldn’t take cordyceps
• Medicinal mushrooms by goal — the hub
• Lab results — beta-glucan
• How to read a certificate of analysis (COA)

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 lupus (SLE), antiphospholipid syndrome or any other medical condition. Lupus requires diagnosis and follow-up by a rheumatologist, including periodic blood and urine tests, and eye examinations for anyone taking hydroxychloroquine. Do not stop, replace or change the dose of hydroxychloroquine, prednisone, immunosuppressants, anticoagulants 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 or any existing medical condition. *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.*