Fungal Supplement May Reduce COVID-19 Vaccine Adverse Effects and Extend Antibody Protection

A natural fungal supplement taken concurrently with a COVID-19 vaccine significantly reduced common adverse effects and helped antibody levels persist for up to 6 months in previously unexposed individuals, according to results of a randomly assigned, double-blind, placebo-controlled clinical trial (NCT04951336) published in BMC Immunology. The findings, led by investigators at UC San Diego School of Medicine, may have meaningful implications for vaccine tolerability, hesitancy reduction, and future pandemic preparedness.^1,2

Study Design and Intervention

The study enrolled 90 adults scheduled to receive a COVID-19 vaccine and randomly assigned them to receive either a 4-day course of “FoTv,” a proprietary mycelium-based oral supplement derived from Fomitopsis officinalis (agarikon) and Trametes versicolor (turkey tail), or matching placebo capsules beginning on the day of vaccination. Researchers assessed safety, reactogenicity, and serum antibody levels at multiple intervals over 6 months. No adverse events were reported, and the supplement was well tolerated throughout the study period.^1,3

The most pronounced effects were observed among "COVID-naive" participants, who are those with no prior SARS-CoV-2 infection or vaccination at enrollment. In this subgroup, those receiving FoTv reported significantly fewer postvaccination adverse effects, including fatigue and myalgia, compared with placebo recipients. Antibody levels in this group continued to rise throughout the 6-month observation window, in contrast to the typical pattern of a peak at approximately 1 month followed by gradual decline.¹

Fungi as Natural Immune Modulators

Turkey tail is among the most extensively studied medicinal fungi in modern pharmacognosy. Its primary bioactive constituents, polysaccharopeptide and polysaccharide-K (PSK), have demonstrated significant immunomodulatory properties in preclinical and clinical settings. In vitro research has shown that turkey tail mycelium triggers robust upregulation of the CD69 activation marker on lymphocytes and monocytes, suggesting direct stimulation of innate immune pathways. The National Cancer Institute has noted that PSK-based preparations derived from T versicolor have been used as immunotherapeutic adjuncts in Japan and China for decades.^4,5

"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,” Gordon Saxe, MD, PhD, MPH, principal investigator and professor in the Department of Family Medicine at UC San Diego, said in a news release.¹

This molecular compatibility may underpin the supplement's ability to modulate, rather than simply amplify, the immune response, potentially explaining why adverse effects decreased while antibody durability improved.¹

Implications for Vaccine Hesitancy and Pandemic Preparedness

Concerns about vaccine adverse effects remain a primary driver of COVID-19 vaccine hesitancy and suboptimal booster uptake. A national survey found that concerns about adverse effects were cited by more than 42% of unboosted US adults as a primary reason for not receiving additional COVID-19 doses. A complementary analysis of US booster reluctance found that concerns about adverse effects ranked second among the most frequently reported barriers to bivalent booster receipt. An intervention that demonstrably reduces reactogenicity without compromising immunogenicity could directly address one of the most stubborn obstacles to COVID-19 vaccination programs.^6,7

The researchers also highlighted scalability as a potential advantage. Because fungal mycelium can be cultivated through standardized, medical-grade fermentation processes, FoTv or similar preparations could theoretically be rapidly produced and deployed in outbreak scenarios. Saxe specifically noted the looming threat of H5N1 avian influenza as a context in which affordable, rapidly scalable immune adjuncts would be particularly valuable.^1,3

For pharmacists, this study adds to a growing body of evidence that mycelium-based natural products warrant serious consideration in integrative and preventive care contexts. Although FoTv is not commercially available as an adjunct therapy, patients may ask about turkey tail and agarikon supplements in the context of vaccine preparation. Counseling should acknowledge the preliminary but promising clinical evidence, the generally favorable safety profile demonstrated in this trial, and the need for further confirmatory research before these agents can be formally recommended alongside vaccination.¹

REFERENCES

1. Saxe G, Smith CN, Golshan S, et al. Polypore mushroom mycelia as an adjunct to COVID-19 vaccination: a randomized clinical trial. BMC Immunol. Published online January 31, 2026. Updated March 3, 2026. https://link.springer.com/article/10.1186/s12865-026-00809-9

2. RCT of mushroom based natural product to enhance immune response to COVID-19 vaccination (MACH19). ClinicalTrials.gov. Updated August 17, 2025. Accessed March 9, 2026. https://clinicaltrials.gov/study/NCT04951336

3. Study finds natural fungal supplement improves COVID-19 vaccine response. News release. University of California San Diego. March 3, 2026. Accessed March 9, 2026. https://www.eurekalert.org/news-releases/1118566

4. Benson KF, Stamets P, Davis R, et al. The mycelium of the Trametes versicolor (turkey tail) mushroom and its fermented substrate each show potent and complementary immune activating properties in vitro. BMC Complement Altern Med. 2019;19(1):342. doi:10.1186/s12906-019-2681-7

5. Medicinal mushrooms (PDQ): health professional version. National Cancer Institute. Updated November 6, 2024. Accessed March 9, 2026. https://www.cancer.gov/about-cancer/treatment/cam/hp/mushrooms-pdq

6. Haeder SF. Assessing past and future COVID-19 vaccine hesitancy in the United States in light of federal policy changes. Health Aff Sch. 2023;1(6):qxad073. doi:10.1093/haschl/qxad073

7. Jacobs ET, Cordova-Marks FM, Farland LV, et al. Understanding low COVID-19 booster uptake among US adults. Vaccine. 2023;41(42):6221-6226. doi:10.1016/j.vaccine.2023.08.080