Cordyceps militaris | Supplementopedia

Overview

Cordyceps militaris is a parasitic fungus that naturally infects insects such as moth larvae and forms a striking orange‑brown fruiting body. In modern nutraceuticals, it is cultivated on grain or liquid media and used primarily as a dietary supplement aimed at supporting energy metabolism, immune function, and exercise performance.

Benefits

Aerobic Capacity and Perceived Exertion: Can improve aerobic capacity and reduce perceived exertion in healthy adults, likely through enhanced oxygen utilization.
Glucose Homeostasis: Supports glucose homeostasis by modestly lowering fasting glucose and improving insulin sensitivity in pre-diabetic subjects.
Antioxidant Defenses: Enhances antioxidant defenses, limiting oxidative damage in both animal models and humans.
Immune Modulation: Modulates immune parameters, increasing natural-killer-cell activity and cytokine balance in healthy volunteers.
Neuroprotection: Protects neuronal cells against oxidative stress, suggesting potential neuro-protective effects that may translate to improved cognitive processing speed.
Effect Size and Duration: Across trials, typical effect sizes are modest (Cohen’s d ≈ 0.3–0.5) and benefits are most pronounced with daily supplementation for ≥ 8 weeks.

How It Works

Principal Bioactive Constituents: The principal bio‑active constituents of Cordyceps militaris are the nucleoside analogue cordycepin (3′‑deoxyadenosine) and a suite of polysaccharides (β‑glucans), ergosterol, and cordycepic acid (d‑mannitol).
Cordycepin Action: Cordycepin enters cells via nucleoside transporters and is phosphorylated to cordycepin‑5′‑triphosphate, which inhibits adenosine‑dependent signaling, leading to AMP‑activated protein kinase (AMPK) activation and downstream enhancement of mitochondrial biogenesis via PGC‑1α.
β-Glucan Action: The β‑glucans bind dectin‑1 and Toll-like receptors on immune cells, triggering NF-κB modulation and increasing cytokine production (e.g., IFN‑γ, IL‑12).
Ergosterol Action: Ergosterol and related sterols act as precursors for endogenous steroid synthesis, contributing to anti‑inflammatory and hormone‑modulating effects.
Overall Effects: Collectively, these pathways increase ATP production, improve oxidative stress handling, and modulate immunity.

Dosage

Typical Dosages: Clinical trials have used 1 g to 3 g of dried fruiting‑body powder or 200–600 mg of standardized extract (≥ 10 % cordycepin) per day.
Administration: A typical regimen is once‑daily, preferably with a meal to improve absorption of the polysaccharides.
Aerobic Performance: For aerobic‑performance enhancement, 1.5 g/day for 8–12 weeks has shown consistent benefits.
Metabolic Control: In metabolic‑control studies, 2 g/day for 12 weeks modestly lowered fasting glucose.
Immune Support: For immune support, 500 mg twice daily of a high‑cordycepin extract is commonly recommended.
Dosage Adjustments: Adjustments (e.g., 500 mg‑1 g) may be needed for athletes seeking rapid ergogenic effects, while lower doses (200 mg) may suffice for general wellness.
Long-Term Use: Continuous use beyond 6 months has not shown cumulative toxicity, but cycling 2–3 months on/1 month off is often advised to prevent tolerance.

Safety & Side Effects

General Tolerance: Cordyceps militaris is well‑tolerated; reported adverse events are mild (gastro‑intestinal upset, mild headache).
Contraindications: Contraindications include autoimmune disease (potential immune stimulation) and pregnancy/lactation, where data are insufficient.
Cautions: Caution is warranted for individuals on immunosuppressants (e.g., corticosteroids, cyclosporine) due to possible additive immunostimulation, and for patients taking anticoagulants (e.g., warfarin) because the polysaccharides may mildly prolong clotting time.
Hypoglycemia: Individuals with hypoglycemia should monitor blood glucose as additive glucose‑lowering effects may occur.
Drug Interactions: No serious drug–herb interactions have been documented, but a 2‑week wash‑out is advisable before major surgery.
Pediatric Use: Children under 12 years have not been studied; avoid use in this group.

Chemistry

Cordycepin (3′‑deoxyadenosine): C₁₀H₁₃N₅O₃, IUPAC: 9‑(2‑deoxy‑β‑D‑ribofuranosyl)adenine. It lacks a 3′‑hydroxyl group, conferring resistance to adenosine‑degrading enzymes.
Cordycepic acid (D‑mannitol): C₆H₁₄O₆, a sugar alcohol that contributes to osmotic balance.
β‑glucans: High‑molecular‑weight polysaccharides (β‑1,3/1,6 linkages) with molecular weights 10⁴–10⁶ Da.
Ergosterol: C₂₈H₄₄O, a sterol precursor for vitamin D₂ synthesis.
Solubility: These molecules are water‑soluble (cordycepin) and partially soluble (β‑glucans), allowing extraction by hot water, ethanol, or super‑critical CO₂ methods.
Interaction: Their structures enable interaction with nucleotide‑binding enzymes and pattern‑recognition receptors.

Sources & Quality

Cultivation Locations: Cordyceps militaris is cultivated primarily in China, Japan, and Korea.
Cultivation Conditions: Cultivated on sterilized grains (e.g., rice, soy) under controlled temperature (20–25 °C) and humidity (70–80 %).
Extraction Methods: Commercial extracts are produced via hot‑water extraction for polysaccharides and ethanol/macroporous resin chromatography for cordycepin enrichment.
Premium Extraction: Premium products employ super‑critical CO₂ for sterol‑rich fractions, preserving bio‑activity.
Quality Criteria: Quality criteria include ≥10 % cordycepin (HPLC‑validated) and low microbial contamination (<10³ CFU/g).
Contamination Control: Certified organic, GMP‑certified farms that use substrate‑free, fungal‑only cultures reduce contamination from host insects.
Testing: Third‑party testing for heavy metals, pesticides, and mycotoxins is essential to ensure safety and potency.