There were also significant reductions in physical fatigue.
The mix, commercially available under the name Restake, consists of five medicinal mushrooms: Hericium erinaceus (Lion’s Mane), Cordyceps militaris, Ganoderma lucidum (Reishi), Lentinula edodes (Shiitake), and Grifola frondosa (Maitake).
These mushrooms have been reported to produce stress-relieving benefits. Lion’s Mane and Maitake, for example, were able to alleviate stress or depressive‑like behaviors by modulating BDNF expression.
Writing in Brain and Behavior, researchers from Malaysia said this was the first study to evaluate this combination of medicinal mushrooms as a potent and safe solution for stress, fatigue and sleep improvement.
Study design
Fifty participants aged 22 to 55 years with stress, anxiety, and sleep issues - including symptoms like headaches, palpitations at rest, frequent sleep disturbances - were recruited for the study, which took place in Malaysia.
The participants also had moderate to severe levels of anxiety and stress based on the State Trait Anxiety Inventory (STAI) and Perceived Stress Scale (PSS).
During the 12-week clinical trial, they were randomized to take two capsules each containing 500mg Restake or a placebo daily.
Every 500mg of Restake includes 25% of proprietary mushroom blend extract and is standardized with over 30% β‐glucan and over 30% total polysaccharides. The study materials were manufactured by Nexus Wise Sdn Bhd, which also funded the study.
To assess the effects of the mushroom mix, blood samples were taken to measure the levels stress hormones like cortisol, adrenocorticotropic hormone (ACTH) and inflammatory biomarkers like c‐reactive protein (CRP).
Questionnaires like Pittsburgh Sleep Quality Index (PSQI), Visual Analog Scale for Fatigue (VAS‐F) and Multidimensional Fatigue Inventory (MFI) were also used to assess levels of stress and anxiety in respondents.
Serum cortisol down
One of the key benefits of the mushroom mix was the significant reduction in serum cortisol and ACTH.
For example, serum cortisol levels were down by 4.4% in the intervention group by week six and further reduced by 5.5% by week 12 of the study in the intervention group.
In contrast, serum cortisol increased slightly by 0.7% and 0.8% in week six and week 12 of the study in the placebo group.
In the same vein, ACTH levels also showed significant reductions in the intervention group, down by 10.5% at week six and 8.1% at week 12.
The placebo group, on the other hand, reported a 0.3% increase in ACTH levels at week six and a 0.2% reduction at week 12.
Like serum cortisol, measuring ACTH levels is one of the common methods to assess psychological stress associated with the HPA axis system.
“When the human body perceives stress, ACTH will trigger the production of cortisol to prepare the body for a fight or flight response. A persistently elevated serum cortisol level throughout the day can be considered an alarming condition; a high level of cortisol could lead to hypothalamic‐pituitary‐adrenal (HPA) axis overactivation and circadian rhythm imbalance, consequently causing sleep disruption and chronic fatigue,” the researchers wrote.
With significant reductions in cortisol and ACTH levels, the mushroom blend has shown to modulate the HPA axis, a key regulator of the body’s stress response.
“The significant reductions in cortisol and ACTH levels further support the adaptogenic potential of the mushroom blend in modulating the hypothalamic‐pituitary‐adrenal (HPA) axis, a key regulator of the body’s stress response," they wrote.
Reduction in CRP levels
Another key finding is the significant reduction in CRP levels, which was down 6.3% in the intervention group, while the placebo group reported a significant increase of 4.9% by week 12 of the study.
Higher CRP levels can increase the release of pro‐inflammatory cytokines, such as IL‐6 and TNF‐α, both of which affect central nervous system signaling, leading to fatigue, mood changes, and reduced motivation.
“Treatment with Restake significantly reduced serum CRP level at 12 weeks (p= 0.042), suggesting anti‐inflammatory effects, supporting its role in mitigating inflammation‐associated, persistent fatigue," the researchers wrote. “Therefore, the present study provides a clear mechanistic approach to reducing the stress‐induced fatigue through anti‐inflammatory activities and the HPA system."
They highlighted that existing studies have shown how shiitake - one of the mushrooms used in the mix - has been reported to reduce inflammation linked to chronic stress.
Maitake, on the other hand, supports glucose metabolism and immune health, while β‐glucan - the key active compound in the mushroom mix could stabilize energy levels and reduce cortisol levels.
Questionnaire findings
Both groups showed significant improvements in anxiety levels based on the questionnaire results; however, the improvements in the intervention group were consistently greater than those of the placebo group.
For example, anxiety levels reported by the intervention group went down by 8.7%, while a reduction of 4.9% was seen in the placebo group based on STAI scores.
Similarly, a greater reduction in PSS was seen in the intervention group, down by 17.8% by week 12, while that of the placebo group fell by only 10.1%.
“These results suggest that the mushroom blend offers a natural and effective intervention for managing stress‐related health issues, particularly those involving dysregulated stress hormones. Future studies should explore its long‐term effects and applicability in clinical populations with chronic stress or related disorders," the researchers concluded.
Source: Brain and Behavior, 2026 Jan;16(1):e71193. doi: 10.1002/brb3.71193. “Adaptogenic Effects of Mushroom Blend Supplementation on Stress, Fatigue, and Sleep: A Randomised, Double-Blind, and Placebo-Controlled Trial.” Authors: Hisamuddin AS et al.
