Can Reishi Prevent Colds and Flu? Clinical Evidence

Reishi & Immune Defense

CD56+ ↑

In a double-blind placebo-controlled trial, Ganoderma lucidum extract increased CD56+ natural killer cell counts in healthy volunteers, the immune cell type most critical for early viral defense.

Wicks et al., Int Immunopharmacol, 2007

CD3+ CD4+ CD8+

all increased in children receiving reishi beta-glucan yogurt for 12 weeks

0 Trials

have measured cold or flu incidence as a primary endpoint with reishi

Dectin-1

the innate immune receptor that recognizes reishi beta-glucans

Wicks et al., Int Immunopharmacol, 2007

View as image ↗

Reishi (Ganoderma lucidum) is the most widely studied medicinal mushroom for immune function, with a research history spanning decades and extending from cell culture through animal models to human clinical trials. The evidence shows that reishi polysaccharides, primarily beta-glucans, modulate multiple arms of the immune system: they increase natural killer cell activity, boost T lymphocyte populations, enhance dendritic cell function, and shift cytokine profiles toward immune activation. What the evidence does not show is whether any of this translates to fewer colds or less severe flu infections. No randomized controlled trial has measured cold or flu incidence as a primary endpoint with reishi supplementation. The immune modulation is real. The clinical consequence for respiratory infections remains an inference, not a measurement. For the comprehensive review, see reishi and the immune system: a comprehensive research review.

Key Takeaways

In a double-blind RCT, Ganoderma lucidum extract increased CD56+ NK cell counts in 16 healthy volunteers over 10 days, though the increase did not reach statistical significance due to small sample size and high variability (Wicks et al., 2007)
Children aged 3-5 receiving reishi beta-glucan-enriched yogurt for 12 weeks showed significantly higher circulating CD3+, CD4+, and CD8+ T lymphocytes than placebo, with over 90% treatment adherence (Henao et al., 2018)
G. lucidum polysaccharides promote innate immune function, humoral immunity, and cellular immunity through effects on B cells, T cells, dendritic cells, macrophages, and NK cells (Wang et al., 2019)
A separate beta-glucan clinical trial found that 900 mg/day of yeast beta-glucan reduced common cold episodes in 162 adults with recurring infections compared to placebo (Auinger et al., 2013)
Yeast beta-glucan at 250 mg/day for 16 weeks reduced the severity of upper respiratory tract infections in healthy adults in a double-blind RCT (Dharsono et al., 2019)
No trial has tested reishi specifically for cold/flu prevention; the evidence gap between immune cell modulation and clinical respiratory protection remains unfilled

The NK Cell Data: Reishi's Most Direct Antiviral Evidence

Natural killer cells are the immune system's first responders against viral infections. They detect and destroy virus-infected cells within hours, before adaptive immunity (T cells, antibodies) has time to activate. NK cell count and cytotoxic activity are strong predictors of susceptibility to viral respiratory infections: people with lower NK cell function get more colds and recover more slowly.

Wicks et al. (2007) conducted the most relevant safety and tolerability trial. Sixteen healthy volunteers received either 2 grams of G. lucidum extract or placebo twice daily for 10 consecutive days in a double-blind design.^[1] No adverse effects were observed. While CD4, CD8, and CD19 (B cell) counts showed no obvious changes, CD56+ cell counts (the marker for NK cells) increased during reishi supplementation and returned to baseline 10 days after stopping.

The NK cell increase did not reach statistical significance, a finding the authors attributed to high inter-individual variability and the small sample size (n=16). This is the critical limitation of the reishi-NK cell literature: the biological signal is present but underpowered. A larger trial with adequate statistical power to detect a meaningful NK cell increase has not been conducted with G. lucidum specifically.

The clinical relevance of an NK cell count increase depends on magnitude and functional consequence. A modest increase in circulating NK cells does not automatically translate to better viral defense. NK cells must also be functionally active (capable of degranulation and cytokine secretion), properly trafficked to mucosal surfaces where respiratory viruses enter, and sustained over the time period of exposure. The Wicks study measured count, not cytotoxic function.

The Pediatric RCT: Beta-Glucans in Children

Henao et al. (2018) conducted a randomized, double-blinded, placebo-controlled trial in 3-5 year old children from Medellin, Colombia, testing yogurt enriched with beta-glucans from G. lucidum.^[2] The primary outcomes were circulating CD8+ T lymphocyte and natural killer cell counts. Secondary outcomes included total lymphocytes, CD3+ and CD4+ T cell counts, serum immunoglobulin A concentrations, cytokine levels, and hematological parameters.

After 12 weeks of daily supplementation, children receiving the beta-glucan yogurt showed significantly higher absolute counts of peripheral blood CD3+, CD4+, and CD8+ T cells compared to placebo. Treatment adherence exceeded 90%, and no safety concerns emerged (no abnormal increases in creatinine or hepatic enzymes).

This is the strongest human RCT evidence for reishi beta-glucan immune modulation. The T lymphocyte increases are directly relevant to adaptive antiviral immunity: CD8+ cytotoxic T cells are responsible for killing virus-infected cells after adaptive immunity activates, and CD4+ helper T cells coordinate the entire adaptive immune response. Higher baseline counts of these cells would theoretically enable faster and stronger responses to viral challenge.

The study did not measure respiratory infection incidence. Whether the T cell increases led to fewer illnesses in these children is unknown. The 12-week duration is sufficient to detect immune cell changes but may not be long enough to accumulate enough infection events to detect a difference in illness rates, particularly in a healthy pediatric population.

The Mechanistic Reviews: How Reishi Modulates Immunity

Wang et al. (2019) published a comprehensive review of Ganoderma's immunomodulating effects, covering both preclinical and clinical evidence.^[3] The immunomodulation spans multiple cell types and pathways:

Macrophages: increased phagocytic activity and cytokine production (TNF-alpha, IL-1, IL-6)
Dendritic cells: enhanced maturation and antigen-presenting capacity
NK cells: increased cytotoxic activity against target cells
T cells: promotion of Th1 differentiation (cellular immunity) and in some contexts Th2 responses
B cells: enhanced antibody production
Regulatory T cells: modulation of immune tolerance

The review acknowledged a critical gap: "evidence-based clinical trials are also needed" to translate these mechanistic findings into clinical outcomes.

Lin et al. (2005) detailed the cellular and molecular mechanisms, identifying that G. lucidum polysaccharides signal through Toll-like receptor 4 (TLR4), Dectin-1, and complement receptor 3 (CR3), the same pathogen recognition receptors that detect bacterial and fungal cell wall components.^[4] This molecular pathway explains why the immune system responds to reishi polysaccharides as if responding to a pathogen: the beta-glucan structure mimics microbial cell wall components, triggering innate immune activation without actual infection. For how this connects to the broader immunology of mushroom beta-glucans, see reishi beta-glucans and immune cell activation.

Beyond Immune Cell Counts: Gut-Immune Axis Effects

Guo et al. (2021) demonstrated that G. lucidum polysaccharides modulate gut microbiota and immune cell function in a colitis model, revealing an indirect pathway through which reishi might affect systemic immunity.^[5] The gut houses approximately 70% of the body's immune cells, and changes in gut microbiota composition directly influence systemic immune tone. If reishi polysaccharides shift the gut microbiome toward compositions that promote anti-inflammatory or immune-enhancing states, the effect on respiratory infection susceptibility could operate through the gut-lung axis rather than through direct immune cell stimulation.

Cai et al. (2017) showed that Ganoderma polysaccharides attenuate microglia-mediated neuroinflammation and modulate microglial phagocytosis, demonstrating that the immunomodulatory effects extend to tissue-resident immune cells beyond the circulation.^[6]

Chen et al. (2024) reviewed Ganoderma's broader therapeutic potential, including its documented antioxidant, anti-inflammatory, immunomodulatory, and anti-aging effects across multiple organ systems, confirming that the immune effects are embedded within a wider pharmacological profile.^[7]

The Yeast Beta-Glucan Bridge: Cold Prevention Data That Exists

While no reishi-specific cold prevention trial exists, structurally similar beta-glucans from baker's yeast (Saccharomyces cerevisiae) have been tested for respiratory infection outcomes.

Auinger et al. (2013) conducted a double-blind, randomized, placebo-controlled, multicentric trial in which 162 healthy adults with a history of recurring infections received 900 mg/day of yeast (1,3)-(1,6)-beta-D-glucan or placebo.^[8] The study found that beta-glucan supplementation reduced the number of common cold episodes and helped "maintain the body's defence against pathogens."

Dharsono et al. (2019) tested 250 mg/day of yeast (1,3)-(1,6)-beta-glucan versus placebo for 16 weeks in a double-blind RCT of healthy adults.^[9] The beta-glucan group experienced reduced severity of upper respiratory tract infections compared to placebo.

These yeast studies are the closest available evidence to what a reishi cold prevention trial might show. Yeast (1,3)-(1,6)-beta-glucans and G. lucidum beta-glucans share structural motifs and bind the same receptors (Dectin-1, CR3). However, they differ in molecular weight, branching patterns, and accompanying bioactive compounds (reishi also contains triterpenoids, proteins, and other immunomodulatory molecules absent from purified yeast beta-glucan). Whether reishi supplementation would replicate, exceed, or fall short of the yeast beta-glucan respiratory infection data is unknown. For how the beta-glucan differences between species affect immune activation, see how reishi modulates innate and adaptive immunity.

The Ganopoly Trial: Safety in a Clinical Setting

Tang et al. (2005) conducted a randomized, double-blind, placebo-controlled study of Ganopoly (a G. lucidum polysaccharide extract) in 132 patients with neurasthenia.^[10] While the primary outcome was fatigue and well-being rather than immune function or infection, the trial provides important safety and tolerability data for reishi polysaccharide supplementation at doses used in clinical settings. The extract was well-tolerated with no serious adverse events, supporting the feasibility of longer-duration trials that could measure respiratory infection outcomes.

What the Evidence Supports and What It Does Not

Evidence type	Finding	Confidence
NK cell increase	CD56+ cells rose with reishi in healthy adults (non-significant, n=16)	Low
T cell increase	CD3+, CD4+, CD8+ significantly increased in children over 12 weeks	Moderate
Immune mechanism	Polysaccharides activate macrophages, DCs, NK cells via TLR4/Dectin-1/CR3	Moderate to high
Cold prevention (reishi)	No trial has measured this	None
Cold prevention (yeast beta-glucan)	Reduced cold episodes and URI severity in two RCTs	Moderate
Safety	Multiple RCTs confirm tolerability with no serious adverse events	Moderate to high

For related immune research across other mushroom species, see Agaricus blazei for immune-compromised patients and reishi for immune support during chemotherapy.

The Bottom Line

Reishi polysaccharides increase NK cell counts, T lymphocyte populations, and dendritic cell function in human clinical trials, with the strongest RCT evidence coming from a pediatric study showing significant T cell increases over 12 weeks. No trial has measured whether these immune changes reduce cold or flu incidence. Yeast beta-glucan (structurally similar) reduced common cold episodes and URI severity in two RCTs, providing indirect support for the hypothesis. The gap between measured immune modulation and clinical respiratory protection remains the central unanswered question.

Frequently Asked Questions

No clinical trial has tested reishi supplementation specifically for cold or flu prevention. Reishi beta-glucans increase NK cell counts and T lymphocyte populations in RCTs (Wicks et al., 2007; Henao et al., 2018), and these immune cells are critical for antiviral defense. Structurally similar yeast beta-glucans reduced common cold episodes in a separate RCT (Auinger et al., 2013). Whether reishi would produce the same clinical benefit is plausible but unconfirmed.

G. lucidum polysaccharides activate innate immune cells (macrophages, dendritic cells, NK cells) through pattern recognition receptors including Dectin-1, TLR4, and complement receptor 3 (Lin et al., 2005). This activation promotes phagocytosis, cytokine production, and antigen presentation, which in turn enhances adaptive immune responses including T cell activation and antibody production (Wang et al., 2019).

Clinical trials have used 2-4 grams of G. lucidum extract daily (Wicks et al., 2007; Tang et al., 2005). The pediatric trial used beta-glucans delivered in yogurt form (Henao et al., 2018). Doses and preparations vary substantially between studies, making it difficult to establish a standardized recommendation. Beta-glucan content, extraction method, and whether fruiting body or spore preparations are used all affect bioactivity.

Multiple randomized controlled trials have evaluated reishi safety. Wicks et al. (2007) found no adverse effects from 4 grams daily for 10 days in healthy volunteers. Tang et al. (2005) demonstrated tolerability in 132 patients over a longer treatment period. Henao et al. (2018) confirmed safety in children over 12 weeks with no abnormal laboratory values. No serious adverse events have been attributed to reishi in published clinical trials.

Both share (1,3)-(1,6)-linked glucose polymer structures that bind Dectin-1 and other immune receptors. They differ in molecular weight, branching patterns, solubility, and accompanying bioactive compounds. Reishi contains triterpenoids, proteins, and other immunomodulatory molecules not present in purified yeast beta-glucan. Whether the cold prevention effects demonstrated with yeast beta-glucan (Auinger et al., 2013; Dharsono et al., 2019) translate directly to reishi is unknown.

Wicks et al. (2007) observed an increase in CD56+ NK cell counts in healthy volunteers taking G. lucidum extract for 10 days, though the increase did not reach statistical significance due to small sample size (n=16) and high inter-individual variability. Preclinical studies consistently show enhanced NK cell cytotoxic activity with reishi polysaccharides (Wang et al., 2019). A larger, adequately powered human trial measuring both NK cell count and functional cytotoxicity is needed.

Sources & References

1RTHM-00123·Wicks, Sheila M et al. (2007). “Safety and tolerability of Ganoderma lucidum in healthy subjects: a double-blind randomized placebo-controlled trial..” The American journal of Chinese medicine.Study breakdown →PubMed →↩
2RTHM-00512·Henao, Sandra Lorena Duque et al. (2018). “Randomized Clinical Trial for the Evaluation of Immune Modulation by Yogurt Enriched with β-Glucans from Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), in Children from Medellin, Colombia..” International journal of medicinal mushrooms.Study breakdown →PubMed →↩
3RTHM-00594·Wang, Xin et al. (2019). “Immunomodulating Effect of Ganoderma (Lingzhi) and Possible Mechanism..” Advances in experimental medicine and biology.Study breakdown →PubMed →↩
4RTHM-00084·Lin, Zhi-Bin (2005). “Cellular and molecular mechanisms of immuno-modulation by Ganoderma lucidum..” Journal of pharmacological sciences.Study breakdown →PubMed →↩
5RTHM-00690·Guo, Cuiling et al. (2021). “Ganoderma lucidum polysaccharide modulates gut microbiota and immune cell function to inhibit inflammation and tumorigenesis in colon..” Carbohydrate polymers.Study breakdown →PubMed →↩
6RTHM-00462·Cai, Qing et al. (2017). “Polysaccharides from Ganoderma lucidum attenuate microglia-mediated neuroinflammation and modulate microglial phagocytosis and behavioural response..” Journal of neuroinflammation.Study breakdown →PubMed →↩
7RTHM-00871·Chen, Xu-Jia et al. (2024). “Therapeutic potential of the medicinal mushroom Ganoderma lucidum against Alzheimer's disease..” Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.Study breakdown →PubMed →↩
8RTHM-00278·Auinger, Annegret et al. (2013). “Yeast (1,3)-(1,6)-beta-glucan helps to maintain the body's defence against pathogens: a double-blind, randomized, placebo-controlled, multicentric study in healthy subjects..” European journal of nutrition.Study breakdown →PubMed →↩
9RTHM-00550·Dharsono, Tanita et al. (2019). “Effects of Yeast (1,3)-(1,6)-Beta-Glucan on Severity of Upper Respiratory Tract Infections: A Double-Blind, Randomized, Placebo-Controlled Study in Healthy Subjects..” Journal of the American College of Nutrition.Study breakdown →PubMed →↩
10RTHM-00088·Tang, Wenbo et al. (2005). “A randomized, double-blind and placebo-controlled study of a Ganoderma lucidum polysaccharide extract in neurasthenia..” Journal of medicinal food.Study breakdown →PubMed →↩