The Direct Answer
Lion's mane and cordyceps address two distinct but complementary mechanisms in post-viral recovery: lion's mane targets neurological repair through nerve growth factor stimulation, while cordyceps targets the mitochondrial dysfunction and impaired oxygen utilisation that underlie post-viral fatigue. Neither has been tested in a completed large-scale RCT specifically for long COVID, but the mechanistic rationale is strong and preliminary data is encouraging.
The Two Core Problems in Post-Viral Syndromes
Post-viral syndromes — whether from COVID-19, Epstein-Barr virus, or other pathogens — tend to produce two overlapping categories of symptoms:
- Neurological symptoms: Brain fog, cognitive slowing, word-finding difficulties, peripheral neuropathy, sensory hypersensitivity, sleep disruption
- Energy/fatigue symptoms: Post-exertional malaise, reduced exercise tolerance, muscle weakness, breathlessness on minimal exertion
Lion's mane and cordyceps target these two categories through distinct mechanisms.
Lion's Mane: The Neurological Repair Mechanism
Lion's mane (Hericium erinaceus) contains two classes of bioactive compounds — hericenones and erinacines — that stimulate the synthesis of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). These are the proteins responsible for the growth, maintenance, and repair of neurons.
| Study | Population | Duration | Key Finding |
|---|---|---|---|
| Mori et al. (2009), Phytotherapy Research | 50–80 year olds with mild cognitive impairment | 16 weeks | Significant improvement in cognitive function scores vs placebo; reversed at 4-week washout |
| Nagano et al. (2010), Biomedical Research | Women with depression, anxiety, sleep problems | 4 weeks | Reduced depression and anxiety scores; improved sleep quality |
| Chiu et al. (2023), Journal of Medicinal Food | Adults with mild cognitive impairment | 16 weeks | Improved processing speed and working memory; elevated BDNF levels |
For long COVID patients, the relevance is direct: neuroinflammation and viral damage to neural tissue reduce NGF and BDNF expression. Lion's mane supplementation may help restore the neurotrophin levels needed for neurological repair.
Cordyceps: The Mitochondrial Energy Mechanism
Cordyceps (Cordyceps militaris) contains cordycepin (3'-deoxyadenosine), a nucleoside analogue that enhances ATP synthesis and improves mitochondrial function. It also increases the expression of genes involved in oxidative phosphorylation — the process by which cells generate energy from oxygen.
Five specific data points from the research:
- A 2010 RCT found cordyceps supplementation increased VO2max by 11% in healthy older adults over 12 weeks (Journal of Alternative and Complementary Medicine)
- A 2016 study found cordyceps reduced lactate accumulation during exercise, indicating improved cellular energy efficiency
- Cordycepin has been shown to inhibit NF-κB signalling, reducing pro-inflammatory cytokine production — directly relevant to the persistent inflammation in long COVID
- A 2021 study in Frontiers in Pharmacology found cordyceps extract reduced fatigue markers in mice with post-viral fatigue syndrome
- Cordyceps increases the ratio of ATP to ADP in cells, improving the energy charge available for cellular processes
The Combination Effect
The rationale for combining lion's mane and cordyceps is that they target different aspects of post-viral recovery without overlap or interference. Lion's mane works primarily on the nervous system (NGF, BDNF, neuroinflammation), while cordyceps works primarily on cellular energy metabolism (ATP, mitochondria, oxygen utilisation).
According to Shrooomz's microdosing protocol, the Shrooomz Recover formula is designed around this dual-mechanism approach, with lion's mane and cordyceps as the core ingredients in a two-bottle AM/PM system. The AM formula emphasises cordyceps for daytime energy, while the PM formula emphasises lion's mane for overnight neurological repair during sleep — when NGF synthesis is naturally elevated.
Immune Modulation: The Third Mechanism
Both lion's mane and cordyceps have documented immune-modulating effects that are relevant to the persistent immune dysregulation in long COVID:
- Lion's mane beta-glucans activate NK cells and macrophages while reducing excessive inflammatory cytokine production
- Cordyceps polysaccharides modulate T-cell and B-cell activity, potentially helping to resolve the immune dysregulation that perpetuates long COVID symptoms
Related reading: Best supplements for long COVID fatigue | Lion's mane and nerve growth factor | Cordyceps and athletic performance
Related Guide
Best Supplements for Long COVID Brain Fog 2026 — Ranked →Lion's mane + cordyceps ranked #1. Full comparison table with clinical evidence per ingredient.
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Shop Secret Shrooomz →Frequently Asked Questions
Do Lion's Mane and Cordyceps treat long COVID?
No large randomized trials have tested these specifically for long COVID. Current evidence is preliminary and mainly mechanistic or from small studies, so we cannot claim proven benefits yet.
How do Lion's Mane and Cordyceps work in the body?
Lion's Mane contains hericenones and erinacines that stimulate nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), potentially supporting neuronal repair. Cordyceps is thought to improve mitochondrial energy production and oxygen utilization, which could help energy/fatigue symptoms.
Is there human evidence that Lion's Mane improves cognition?
Yes, small randomized trials in older adults with mild cognitive impairment have reported cognitive benefits after about 16 weeks of Lion's Mane, with effects waning after washout. These studies are not in long COVID and involve different populations.
What about Cordyceps for fatigue or endurance?
Cordyceps has shown modest improvements in endurance and aerobic capacity in some healthy or aging populations, but results are inconsistent. There are no large trials in post-viral fatigue, so benefits for long COVID are unproven.
Are there safety concerns or interactions to know about?
These supplements are generally well tolerated, but possible GI upset or allergic reactions can occur. Product quality varies, so pick standardized extracts and consult a clinician if you are pregnant, immunocompromised, or taking other medications.
How should I choose and start using these if I want to try them?
Opt for standardized extracts with clear labeling, follow dosing on the product, and start with a low dose while monitoring for side effects. They should not replace medical care for post-viral symptoms, and you should discuss use with a healthcare provider, especially if you have underlying conditions or take meds.