Adaptogenic Mushrooms and Stress: Cortisol, the HPA Axis & Reishi
Adaptogenic mushrooms for stress: how reishi, cortisol and the HPA axis actually connect — and what the human evidence does and doesn't show about resilience.
10/6/20266 min read
KNOWLEDGE SERIES
Adaptogenic Mushrooms and Stress: Cortisol, the HPA Axis and What the Science Actually Supports
The word "adaptogen" appears on a remarkable number of wellness products. It implies something specific and appealing: a substance that helps the body adapt to stress, normalise its responses, and build resilience over time.
The term is now used so broadly, and applied to so many ingredients, that its original meaning has been substantially diluted. To assess whether functional mushrooms genuinely qualify — and if so, which ones and through what mechanism — requires going back to where the concept came from.
What an Adaptogen Actually Is
The term was coined in 1947 by Soviet pharmacologist Nikolai Lazarev, who was studying substances that could increase the body's nonspecific resistance to adverse influences across a wide range of physical, chemical, and biological stressors.
The formal criteria were established two decades later by Brekhman and Dardymov in a landmark paper published in the Annual Review of Pharmacology in 1969. Three conditions must be met (¹):
First, non-toxicity. The substance must not significantly disturb normal physiological function. It should be safe for extended use.
Second, a non-specific response. It must increase resistance to multiple different categories of stress, not just one. A compound that helps only with cold exposure, or only with exercise fatigue, is not an adaptogen — it is a specific agent for a specific stressor.
Third, a normalising effect. It must move the organism toward homeostasis in a bidirectional manner — reducing what is excessive and supporting what is deficient, rather than simply pushing in one direction.
These are demanding criteria. Many substances marketed as adaptogens meet one or two of them at best.
Of the eight varieties in the mitovito range, Reishi most directly satisfies the formal definition. And even for Reishi, the human evidence base is thinner than the marketing language across this industry typically implies.
The HPA Axis: The Central Stress System
To understand what an adaptogen is supposed to do, you need to understand the system it acts on.
The hypothalamic-pituitary-adrenal axis is the body's primary stress-response machinery. When the brain perceives a stressor — whether physical, like cold or injury or exercise, or psychological, like work pressure or conflict — the hypothalamus releases corticotropin-releasing hormone. That signals the pituitary gland to release adrenocorticotropic hormone. ACTH travels to the adrenal glands, where it triggers production and release of cortisol (²).
Cortisol is not the villain it is often portrayed as. In the short term it does essential work: mobilising glucose for immediate energy, sharpening sensory attention, temporarily suppressing non-urgent processes including digestion and immune activity, and preparing the body for action. These are appropriate, adaptive responses to genuine threat.
The problem is chronic activation. When the HPA axis remains engaged for extended periods without adequate recovery, sustained cortisol elevation is associated with suppressed immune function, disrupted sleep architecture, impaired memory consolidation, elevated inflammatory markers, and metabolic dysregulation (³).
A true adaptogen acting on the HPA axis would help restore the normal diurnal cortisol rhythm — supporting the morning cortisol awakening response, which should be high, while facilitating the evening decline, which should be low enough to permit melatonin release and sleep onset. Bidirectional. Normalising. Not simply suppressive.
Reishi and the HPA Axis
Reishi's ganoderic acid triterpenes are the most studied functional mushroom compounds in this context.
Animal studies have demonstrated that ganoderic acids interact with corticotropin-releasing factor receptors and modulate ACTH secretion — the second step in the HPA cascade. They also interact with GABA-A receptor complexes, providing a plausible neurological mechanism for the calming and sleep-facilitating effects reported in human trials (⁴).
The human clinical evidence is limited but directionally consistent. The Tang 2005 trial in patients with neurasthenia showed significant fatigue reduction and improved subjective wellbeing over eight weeks. The Zhao 2012 study in cancer-related fatigue showed significant improvements in fatigue, anxiety, and sleep quality. The Chu 2023 systematic review found consistent directional evidence for improved sleep quality across ten controlled studies (⁵).
Here is what the human evidence has not yet established: a direct, measured cortisol-lowering effect in healthy adults with blood cortisol as the primary outcome.
The HPA mechanism is supported primarily by animal research and in vitro work. The human trials measure downstream consequences — fatigue scores, sleep quality, anxiety ratings — rather than cortisol itself.
Those downstream outcomes are clinically meaningful. People care about sleeping better and feeling less exhausted far more than they care about a hormone measurement. But "Reishi lowers your cortisol" remains, in humans, an inference rather than a demonstrated finding, and we would rather you knew which one you were reading.
Lion's Mane and Stress: A Different Mechanism
Lion's Mane is not a classical adaptogen under the Brekhman-Dardymov criteria. But it has produced stress-relevant results in human research through what appears to be an entirely different route.
The Docherty 2023 trial measured subjective stress alongside cognitive performance and found a trend toward reduced stress scores that narrowly missed conventional statistical significance (p=0.051) — a result worth reporting honestly as a trend rather than a finding.
A 2010 Japanese study by Nagano and colleagues published in Biomedical Research examined 30 female university students consuming Lion's Mane cookies daily for four weeks. Compared to placebo, the Lion's Mane group showed significant reductions in anxiety and irritation scores (⁶).
The mechanism here is likely distinct from Reishi's HPA pathway. Lion's Mane's NGF-stimulating compounds may support the neuroplasticity that underlies stress resilience — the brain's capacity to adapt to difficult experiences without being structurally reshaped by them.
Chronic stress is associated with hippocampal atrophy. Compounds that support neuronal growth factor synthesis operate on precisely the tissue that chronic cortisol elevation damages. That is a coherent and interesting mechanism, and it is complementary to rather than duplicative of the Reishi pathway.
Cordyceps and Physical Stress Adaptation
Cordyceps fits the classical adaptogen criteria most clearly in the domain of physical stress — specifically exercise and hypoxia.
The capacity to improve VO₂ max, support mitochondrial ATP synthesis, and reduce exercise-induced oxidative stress represents genuine non-specific physical stress adaptation. The traditional use of Cordyceps by Tibetan herders working at altitude — where oxygen availability is the defining physiological stressor — is entirely consistent with this profile (⁷).
It is a narrower form of adaptogenic activity than Reishi's, confined largely to physical rather than psychological stress. But within that domain it is arguably the best-evidenced adaptogenic claim in the range.
What This Means Practically
If your primary concern is stress and sleep, Reishi is the variety with the most direct mechanistic and clinical support. Evening, in warm oat milk, consistently.
If your concern is stress-related cognitive difficulty — the mental fog and impaired concentration that accompany sustained pressure — Lion's Mane addresses a different part of the same problem through neuroplasticity rather than cortisol.
If your stress is primarily physical — training load, altitude, physical demand — Cordyceps has the strongest case.
Many people find that stress presents across more than one of these domains simultaneously, which is why the cognitive stack described in our ritual article pairs FOCUS in the morning with SERENITY in the evening.
The Honest Picture
Functional mushrooms — particularly Reishi, Lion's Mane, and Cordyceps — have credible biological mechanisms and directionally consistent human evidence for stress resilience.
The evidence is most robust for downstream outcomes and less firmly established for cortisol as a measured biomarker in healthy adults.
They are not acute anxiolytics. They do not produce the immediate calming effect of pharmaceutical anxiety medication, and anyone expecting that will be disappointed.
Their benefit appears to be the gradual establishment of a more regulated baseline stress response across weeks of consistent use — which is, in fact, exactly what the original 1969 adaptogen definition described. The concept was built for substances that work this way.
If you are experiencing significant, persistent stress or anxiety that interferes with your daily functioning, please speak with a healthcare practitioner. Functional mushrooms are food ingredients that may support resilience. They are not a treatment for a clinical condition, and no honest brand should suggest otherwise.
Sources
(1) Brekhman II, Dardymov IV. (1969). New substances of plant origin which increase nonspecific resistance. Annual Review of Pharmacology, 9, 419–430.
(2) Tsigos C, Chrousos GP. (2002). Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress. Journal of Psychosomatic Research, 53(4), 865–871.
(3) Sapolsky RM. (2004). Why Zebras Don't Get Ulcers. Henry Holt and Company.
(4) Tang W et al. (2012). Ganoderic acids and their immunomodulating activities. Journal of Ethnopharmacology, 144(1), 208–215.
(5) Tang W et al. (2005). Journal of Medicinal Food, 8(1), 53–58; Zhao H et al. (2012). Evidence-Based Complementary and Alternative Medicine, 2012, 809614; Chu QP et al. (2023). Frontiers in Pharmacology, 14, 1207940.
(6) Nagano M et al. (2010). Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake. Biomedical Research, 31(4), 231–237.
(7) Hirsch KR et al. (2017). Journal of Dietary Supplements, 14(1), 42–53.
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