Researchers at University California San Diego School of Medicine have found that a natural fungal supplement taken at the time of COVID-19 vaccination reduced short-term vaccine side effects and helped antibodies — the body's natural immune defenders — last longer in people who had not previously been exposed to the virus.
The study, a randomized, double-blind, placebo-controlled clinical trial, was published March 3, 2026, in BMC Immunology. It tested a four-day oral supplement, "FoTv," made from the mycelium — the root-like network — of two types of medicinal fungi: Fomitopsis officinalis and Trametes versicolor (FoTv). Participants began taking the supplement on the same day they received their vaccine.
Natural products are commonly used around the world but are rarely studied in large, carefully controlled clinical trials. "Natural products are widely used, but they are rarely tested at this level. We wanted objective data," said Gordon Saxe, MD, PhD, MPH, the study's principal investigator and a professor in the Department of Family Medicine at UC San Diego School of Medicine.
Many modern vaccines use substances called immune adjuncts to help the body produce a stronger antibody response. Most of these adjuncts are synthetic. They boost antibody production, but they can also increase side effects such as fever, chills, fatigue and muscle aches. Scientists have long been searching for an immune adjunct that can strengthen vaccine protection without increasing short-term side effects.
"Our goal was to see whether FoTv, a possible natural immune regulator, could decrease vaccine side effects while preserving or increasing antibody levels and helping vaccine protection last longer," Saxe said. "The results suggest that it may have done both."
The study included 90 adults receiving a COVID-19 vaccine who were randomly assigned to take either FoTv or placebo capsules by mouth for four days, starting on the day of vaccination. Researchers measured safety, short-term vaccine side effects and antibody levels at intervals up to six months. FoTv was found to be safe and no adverse events were reported.
The strongest results were seen in participants who were "COVID-naïve," meaning they had never had COVID-19 and had not been vaccinated before joining the study. In this group, those who took FoTv had significantly fewer side effects after vaccination compared with those taking the placebo. In addition, antibody levels in COVID-naïve participants who took the supplement continued to increase over the six months of the study.
"Antibody levels usually rise, peak about one month after vaccination, and then slowly decrease," Saxe said. "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."
The researchers noted that a natural supplement that decreased side effects while improving antibody durability might help reduce vaccine hesitancy and possibly reduce the need for frequent booster shots.
Because fungal mycelium can be grown using standardized, scalable and medical-grade production methods, researchers believe this approach could play a role in preparing for future infectious disease outbreaks including activity against influenza A strains such as H5N1 ("bird flu").
"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," Saxe said. "This study shows that FoTv, a carefully tested natural immune modulator, may help support that goal. Humans and fungi are evolutionarily descended from a common ancestor and human immune cells have receptors that bind and are activated by compounds found in fungi. In fact, fungi such as FoTv may have an array of compounds and potential medical uses that we are only now beginning to understand."
Saxe emphasized that additional studies are needed to confirm the findings and better understand how the supplement works.
Link to full study: https://link.springer.com/article/10.1186/s12865-026-00809-9
Additional co-authors on the study include: Christine N. Smith from UC San Diego School of Medicine and UC Irvine; Shahrokh Golshan, Tatyana Shekhtman, Lauray MacElhern, Daniel Slater and Phoebe Senowitz from UC San Diego School of Medicine; Zolton J. Bair and Chase Beathard from Fungi Perfecti, LLC; Renee A. Davis from Fungi Perfecti, LLC and University of Washington; Andrew Shubov and Lan K. Kao from UCLA; and Stephen Wilson from Botnar Institute of Immune Engineering.
The study was funded, in part, by a grant from the University of California San Diego Krupp Endowed Fund; Jonathan and Kathleen Altman Foundation; Fungi Perfecti, LLC; Sacharuna Foundation; Jesy Foundation and Texas Instruments Foundation.
Mushroom mycelium of Agarikon and Turkey Tail (FoTv) used in this study was provided by Fungi Perfecti, LLC of Olympia, Washington.
The authors declare no competing interests. Saxe serves on the board of the Krupp Endowed Fund, but was recused from decision-making regarding this grant award.
