Fungal supplement linked to fewer COVID vaccine side effects, enduring antibodies

A randomised clinical trial at the University of California San Diego School of Medicine has reported that a short course of a medicinal fungal mycelium supplement taken alongside COVID-19 vaccination reduced short-term side effects and supported sustained antibody responses in people with no prior exposure to the virus

Researchers at the University of California San Diego School of Medicine, California, USA, have reported that a natural fungal supplement taken at the time of COVID-19 vaccination reduced short-term vaccine side effects and supported sustained antibody responses in individuals who had not previously encountered the virus.

The investigation took the form of a randomised, double-blind, placebo-controlled clinical trial designed to assess both safety and immune responses associated with a short course of a medicinal fungal product.

The supplement – referred to in the study as FoTv – consists of mycelium derived from two medicinal fungi, Fomitopsis officinalis and Trametes versicolor. Mycelium forms the root-like structural network that supports fungal growth and contains numerous bioactive compounds that researchers believe may influence immune signalling pathways. Participants began to take the oral supplement on the same day they received their COVID-19 vaccination and continued to take capsules for four days.

Natural products have long formed part of traditional medical practice in many regions of the world. Despite widespread use, rigorous clinical evaluation under controlled trial conditions has remained relatively uncommon. Investigators in this study sought to address that gap by subjecting a fungal-derived supplement to the same methodological standards used to assess pharmaceutical agents.

“Natural products are widely used but they are rarely tested at this level. We wanted [to gather] objective data,” said Dr. Gordon Saxe, the study’s principal investigator and professor in the Department of Family Medicine at the University of California San Diego School of Medicine.

Many modern vaccines contain substances known as immune adjuncts – or ‘adjuvants’ – which stimulate the immune system to produce a stronger antibody response. The most currently used adjuvants are synthetic compounds. Although effective at boosting immune activation, these substances may also contribute to short-term reactions such as fever, chills, fatigue and muscle pain. For several decades, immunologists have attempted to identify agents capable of strengthening vaccine responses while limiting these undesirable effects.

“Our goal was to see whether FoTv, a possible natural immune regulator, could decrease vaccine side effects while preserve or increase antibody levels and help vaccine protection last longer. The results suggest that it may have done both,” Saxe said.

The clinical trial included 90 adults who received a COVID-19 vaccine. Participants were randomly assigned to receive either FoTv capsules or placebo capsules taken orally for four days beginning on the day of vaccination. Researchers evaluated safety outcomes, recorded short-term post-vaccination symptoms and measured antibody responses at multiple intervals extending to six months after immunisation.

Investigators reported that the supplement appeared safe. No adverse events occurred during the study period among participants who received FoTv.

The most pronounced effects appeared among participants described as ‘COVID-naïve’ – individuals who had neither previously contracted the virus nor received any earlier vaccination against it. Within this group, those who received the fungal supplement experienced significantly fewer post-vaccination side effects compared with individuals who received placebo.

Researchers also observed a striking difference in antibody dynamics. In most vaccinated individuals antibody levels rise after immunisation, reach a peak approximately one month later and then gradually decline over time. Among COVID-naïve participants who received the fungal supplement, antibody concentrations continued to increase throughout the six-month monitoring period.

“Antibody levels usually rise, peak about one month after vaccination, and then slowly decrease.

“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.

If confirmed in larger trials, the investigators suggested that a supplement capable of reducing short-term vaccine reactions while strengthening long-term immune protection could offer practical public health advantages. Reduced side effects may increase acceptance among individuals who remain hesitant to receive vaccines. At the same time, more durable antibody responses could potentially reduce reliance on repeated booster immunisations.

Fungal mycelium also offers advantages from a manufacturing perspective. Mycelial cultures can grow under highly controlled conditions and scale readily through established fermentation techniques. Such characteristics may allow rapid production of standardised biological products in response to emerging infectious threats.

The research team proposed that the approach could prove relevant for preparedness efforts against future outbreaks, including strains of influenza A such as H5N1 avian influenza.

“With emerging infectious threats such as H5N1 avian influenza on the horizon, we need affordable and rapidly scalable tools that can strengthen vaccines without increase in 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 activate in response to 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,” he concluded.

The investigators emphasised that the findings remain preliminary. Larger and more diverse clinical trials will be required to confirm the observed effects and to clarify the biological mechanisms that may underpin the immune responses associated with fungal mycelium supplementation.

Nonetheless, the study has added to a growing body of research that explores how biologically derived compounds – particularly those produced by fungi – may influence human immunity.

For further reading please visit: 10.1186/s12865-026-00809-9