Mushroom Supplement Reduced COVID Vaccine Side Effects and Boosted Antibodies

Within hours of a COVID-19 jab, your immune system is already overreacting. Inflammatory signals flood the injection site, white blood cells pile in, and the result is that familiar catalogue of misery: sore arm, fatigue, fever, chills. For roughly 30 percent of Americans surveyed during the initial vaccine rollout, those side effects were reason enough to skip the needle altogether. The immune system, it turns out, doesn’t always know when to stop shouting.

A small clinical trial now suggests that a supplement made from the root-like networks of two mushroom species could dial down that inflammatory noise without weakening the body’s actual defences. If anything, it might strengthen them.

The study, published in BMC Immunology, tested a four-day course of capsules containing freeze-dried mycelium from Fomitopsis officinalis (agarikon, a polypore fungus with a long folk-medicine pedigree) and Trametes versicolor (turkey tail, already studied in cancer trials). Ninety adults in San Diego received the supplement or a visually identical rice-flour placebo starting on the day of their COVID-19 vaccination, eight capsules three times daily. That is a hefty dose, some 12 grams of fungal material a day, though the regimen lasted only four days. Gordon Saxe, the study’s principal investigator and a professor of family medicine at UC San Diego, said the team was determined to get clean data on a product class that usually trades on anecdote. “Natural products are widely used, but they are rarely tested at this level,” he said. “We wanted objective data.”

The headline finding is specific to one subgroup: people who had never been exposed to COVID-19 before, either through infection or vaccination. The researchers called them “COVID-naïve.”

In those participants, the mushroom supplement significantly cut the number of side effects reported on days three and five after the jab compared with placebo. Participants who had previous COVID exposure showed no such benefit, which the researchers attribute to the different immunological dynamics at play when the body has already encountered the virus’s antigens. “In this group, we saw a significant decrease in vaccine side effects while, remarkably, antibody levels continued to increase up to the six-month mark,” Saxe said.

That antibody trajectory is the more intriguing part of the results. Normally, antibody levels climb after vaccination, peak at roughly one month, then gradually fall off. In the COVID-naïve group taking the mushroom supplement, receptor-binding domain antibodies kept rising from day 14 through to the six-month endpoint. The COVID-naïve placebo group, and both groups of previously exposed participants, did not show the same pattern.

The proposed mechanism leans on what immunologists already know about fungal biology. Polypore fungi contain compounds, particularly beta-glucans and polysaccharopeptides, that human immune cells recognise through receptors called dectins. Earlier mouse studies found that a mushroom extract given alongside an H5N1 bird flu vaccine boosted antibody production and, perhaps more importantly, induced cross-protection against variant strains the mice had never encountered. The thinking is that fungal compounds may increase production of IL-1 receptor antagonist, a molecule that tamps down the acute inflammatory spike while still allowing the slower, more durable work of germinal centre B-cell maturation and memory formation to proceed. Less inflammation up front; better long-term memory. In theory, anyway.

There are some significant caveats worth lingering on. The trial enrolled 90 people total, and the COVID-naïve subgroup where all the interesting results appeared was small: 19 people on the supplement, 11 on placebo. The study measured binding antibodies only, not neutralising antibodies, so we don’t know for certain that the immune response it detected would actually stop infection. And Fungi Perfecti, the company that manufactures the supplement, provided both financial support and the capsules used in the trial, with three of the paper’s co-authors listed as company employees (though the authors declare no competing interests, and Fungi Perfecti staff contributed only to mycology literature review and writing, not to data analysis).

Saxe frames the work as a proof of concept rather than a finished product. “With emerging infectious threats such as H5N1 avian influenza on the horizon, we need affordable and rapidly scalable tools that can strengthen vaccines without increasing their side effects,” he said. Fungal mycelium can be cultivated using solid-state fermentation at industrial scale, which makes it considerably cheaper and faster to produce than synthetic adjuvants; and agarikon mycelium has already shown antiviral activity against H5N1 in lab studies, though that is a long way from demonstrating clinical benefit in people.

The broader idea here, using fungi as a kind of immune tuning fork rather than a blunt amplifier, is genuinely interesting. A vaccine adjunct that reduced side effects while preserving or extending antibody durability could, in principle, chip away at the hesitancy problem that dogged COVID-19 vaccination campaigns worldwide. It could also mean fewer boosters. Could.

But 30 participants in a subgroup analysis is not the foundation you build clinical guidelines on. What this trial really demonstrates is that the concept is safe, feasible, and worth testing properly, in a larger cohort, with neutralising antibody assays, and ideally with some measure of the inflammatory and memory-cell markers that would confirm whether the proposed mechanism actually holds up. Whether mushrooms can genuinely tune the immune system is still, for now, an open question with a promising first data point.

Study link: https://link.springer.com/article/10.1186/s12865-026-00809-9