Medicinal Mushroom Blend Shows Clinical Promise for Stress and Sleep

Can Medicinal Mushrooms Revolutionize Stress and Sleep?

Medicinal mushroom blend Restake demonstrates significant stress reduction and sleep improvements in clinical trial

A new clinical trial has revealed that Restake, a proprietary blend of five medicinal mushrooms, significantly reduces stress biomarkers and improves sleep quality in adults experiencing moderate to severe stress symptoms. The 12-week, double-blind, randomized, placebo-controlled study conducted in Malaysia demonstrated notable reductions in cortisol and adrenocorticotropic hormone (ACTH) levels, alongside improvements in anxiety, depression, fatigue, and sleep parameters.

How Was the Study Designed to Validate Restake?

The study, involving 50 participants aged 22-55 with stress-related symptoms, tested a standardized blend containing Lion's Mane (Hericium erinaceus), Cordyceps militaris, Reishi (Ganoderma lucidum), Shiitake (Lentinula edodes), and Maitake (Grifola frondosa) mushrooms. The formulation was standardized to contain more than 30% β-glucan, a polysaccharide known for its immunomodulatory and anti-inflammatory properties. Participants received either 500mg Restake capsules or identical-looking placebo twice daily. The trial measured both objective biomarkers and subjective questionnaire responses at baseline, 6 weeks, and 12 weeks.

Results showed the Restake group experienced significant reductions in serum cortisol (5.5% decrease) and ACTH (8.1% decrease) compared to minimal changes in the placebo group. Anxiety scores measured by the State-Trait Anxiety Inventory and Hamilton Anxiety Scale decreased by 8.7% and 33.5%, respectively. The Beck Depression Inventory showed a 16.8% improvement in the treatment group compared to a 4.1% worsening in the placebo group. Notably, these stress-reducing effects were observed as early as 6 weeks into the intervention.

Sleep quality, assessed using the Pittsburgh Sleep Quality Index (PSQI), improved by 11.1% in the Restake group versus just 1.0% in the placebo group. Physical fatigue showed the most significant improvement among fatigue measures, with a 9.2% reduction compared to 2.1% in the placebo group. The researchers also noted significant changes in C-reactive protein (CRP) and norepinephrine levels, suggesting anti-inflammatory effects and autonomic nervous system modulation.

Key Study Results: In a 12-week clinical trial, Restake—a blend of five medicinal mushrooms standardized to >30% β-glucan—demonstrated significant benefits for adults with moderate to severe stress:
  • Stress biomarkers: 5.5% decrease in cortisol and 8.1% decrease in ACTH
  • Mental health: Anxiety reduced by 8.7-33.5%; depression improved by 16.8% (vs. 4.1% worsening in placebo)
  • Sleep quality: 11.1% improvement on Pittsburgh Sleep Quality Index (vs. 1.0% in placebo)
  • Physical fatigue: 9.2% reduction compared to 2.1% in placebo group
  • Safety: No significant adverse events reported, with excellent participant adherence (>80%)

What Do the Experts Say About Restake?

"The findings demonstrate Restake's adaptogenic potential in modulating the hypothalamic-pituitary-adrenal axis, a key regulator of the body's stress response," the researchers noted. "The improvement in inflammatory markers supported by significant sleep quality enhancement indicates the effectiveness of Restake in managing moderate to severe fatigue and sleep disturbances."

What Are the Mechanisms and Safety Outcomes of Restake?

The study points to the β-glucans in Restake as potential key active compounds, which may work by interacting with dectin-1 receptors on immune cells, reducing NF-κB signaling and inflammatory cytokine production. Individual mushroom components may contribute specific benefits – Lion's Mane promoting neural health by stimulating nerve growth factor, Maitake supporting glucose metabolism and immune health, and Reishi potentially improving sleep via gut microbiota modulation.

The researchers employed a comprehensive array of validated assessment tools, including the Perceived Stress Scale (PSS), Visual Analog Scale for Fatigue (VAS-F), and Multidimensional Fatigue Inventory (MFI) to evaluate various dimensions of participant wellbeing. Participants were required to demonstrate moderate to severe chronic fatigue symptoms with MFI scores of 7 or higher in the subscales for general, physical, or mental fatigue to qualify for the study. The trial excluded individuals with significant medical conditions, pregnant or breastfeeding women, those taking medications that could interfere with sleep or stress biomarkers, and people with diagnosed sleep disorders.

Safety assessments revealed no significant adverse events, with all measured parameters remaining within normal reference ranges throughout the study. The researchers noted high adherence rates, with 90% of participants consuming more than 80% of the provided capsules.

Important: Restake contains five medicinal mushrooms with complementary mechanisms of action: Lion's Mane (neural health via nerve growth factor stimulation), Cordyceps militaris, Reishi (sleep improvement through gut microbiota modulation), Shiitake, and Maitake (immune and glucose metabolism support). The formulation's β-glucans work by interacting with dectin-1 receptors on immune cells, reducing inflammatory signaling and cytokine production. This multi-targeted approach offers a natural alternative to conventional pharmaceuticals for managing stress, anxiety, and sleep disturbances—conditions affecting approximately 27-28% of the global population.

This trial adds to growing interest in adaptogens and natural supplements for stress management. Unlike conventional pharmaceuticals for anxiety and depression, which often come with significant side effects, Restake offers a natural approach with multiple mechanisms of action. The researchers suggest future studies should explore long-term effects and applications in clinical populations with chronic stress-related disorders.

The study comes amid increasing consumer demand for natural stress management solutions and rising healthcare costs associated with stress-related conditions. According to the World Health Organization, stress-related disorders affect a significant proportion of the global population, with prevalence rates of 28.0% for depression, 26.9% for anxiety, and 27.6% for sleep disturbances. The adaptogenic supplement market has been expanding rapidly, with projections suggesting continued growth as more consumers seek alternatives to conventional medications.

Industry Context: This study represents part of a broader trend in the nutraceutical and functional food industry toward evidence-based natural products. While traditional herbal adaptogens like ashwagandha and rhodiola have dominated the market, medicinal mushrooms are gaining significant attention for their multiple bioactive compounds and comprehensive health benefits. The positive results from this controlled trial may accelerate interest in fungal-based adaptogenic formulations, particularly as consumers increasingly seek natural solutions for stress, sleep, and immune support in the post-pandemic landscape.

Summary

A 12-week clinical trial conducted in Malaysia has demonstrated that Restake, a proprietary blend of five medicinal mushrooms, significantly reduces stress biomarkers and improves sleep quality in adults experiencing moderate to severe stress. The double-blind, randomized, placebo-controlled study involving 50 participants aged 22-55 tested a standardized formulation containing Lion's Mane, Cordyceps militaris, Reishi, Shiitake, and Maitake mushrooms, standardized to more than 30% β-glucan content. Results showed the Restake group experienced a 5.5% decrease in serum cortisol and an 8.1% decrease in adrenocorticotropic hormone compared to minimal changes in the placebo group. Anxiety scores decreased by 8.7% to 33.5% depending on the assessment tool used, while depression scores improved by 16.8% in the treatment group compared to a 4.1% worsening in the placebo group. Sleep quality, measured by the Pittsburgh Sleep Quality Index, improved by 11.1% in the Restake group versus just 1.0% in placebo, with physical fatigue showing a 9.2% reduction. The study also noted significant changes in C-reactive protein and norepinephrine levels, suggesting anti-inflammatory effects and autonomic nervous system modulation. Researchers attribute these benefits to β-glucans interacting with immune cell receptors and individual mushroom components contributing specific effects, such as Lion's Mane promoting neural health and Reishi potentially improving sleep via gut microbiota modulation. Safety assessments revealed no significant adverse events, with all parameters remaining within normal ranges and participant adherence exceeding 80%. The findings add to growing evidence for natural adaptogens as alternatives to conventional pharmaceuticals for stress management, particularly as consumer demand for such solutions continues to rise amid increasing prevalence of stress-related disorders affecting approximately 27-28% of the global population.

PMCID
12808922