Written by Tabish Mehraj, PhD. In this study, the Y10M group showed a significant improvement in cognition according to the MoCA-J score compared with the placebo and C5304 groups. Natural killer cell activity was increased in the Y10M group, and there was a positive correlation with the MoCA-J score. This study showed that consumption of maitake mushrooms improves cognition in healthy older adults.

Maitake mushroom (Grifola frondosa) is an edible mushroom that has attracted scientific interest because of its potential effects on immune and cognitive health. There are bioactive components, such as ergosterol and β-glucans, that contribute to its biological activities. Although pre-clinical research on cognitive function remains limited, maitake may influence cognition. Age-related changes in cognitive function are a significant concern, making it valuable to investigate dietary approaches to help maintain cognitive health in older adults. This study evaluated the safety and effects of consuming bread containing two different maitake mushroom strains on cognitive function and natural killer (NK) cell activation in healthy older Japanese adults.

This randomized, double-blind, placebo-controlled trial evaluated 47 healthy Japanese adults aged 60-85 years over 18 weeks. Participants were assigned to one of three groups: bread containing 50 g of maitake mushroom strain Y10M (n = 16), bread containing 50 g of strain C5304 (n = 17), or placebo bread without maitake mushrooms (n = 14). Cognitive function was assessed using the Japanese version of the Mini-Mental State Examination (MMSE), Hasegawa’s Montreal Cognitive Assessment (MoCA-J), and the Dementia Scale (HDS-R). NK cell activation was assessed by measuring CD69 expression using flow cytometry. Blood biochemical parameters, dietary intake, and serum ergosterol concentrations were also evaluated.

Results/Key Findings

• Cognitive function: Participants consuming bread containing the Y10M strain demonstrated significant improvements in MoCA-J total and memory scores versus placebo after 18 weeks, whereas the C5304 strain did not produce significant cognitive benefits (p = 0.045, p = 0.024, respectively). C5304 showed no significant benefit, and neither MMSE nor HDS-R scores differed significantly between groups.
• NK cell activation: Y10M increased CD69 expression in total NK cells and CD56^dim NK cells. Changes in CD69 expression correlated positively with MoCA-J scores (p = 0.027 and p = 0.026, respectively), suggesting a possible link between immune activation (via NK cell activation) and cognitive performance. Adherence and absorption: Serum ergosterol levels increased significantly in both maitake groups versus placebo (p < 0.001), supporting exposure to mushroom-derived constituents. Adherence was high (96–98%).
• Safety: No participants discontinued due to adverse effects. Liver and kidney markers, blood pressure, and most hematological parameters remained within standard ranges, with no clinically concerning changes attributed to maitake.

The randomized, double-blind, placebo-controlled design reduced the risk of selection and assessment bias. The use of two maitake strains enabled comparison of potentially strain-specific effects. Multiple validated cognitive assessment tools were employed, and biochemical confirmation of intake strengthened the assessment of intervention adherence. The study also evaluated immune markers and safety parameters alongside cognitive outcomes, providing preliminary evidence of potential efficacy and tolerability. However, there are a few limitations to the study, including the small, geographically restricted population of healthy older Japanese adults used as subjects, which limits generalizability to other populations and to individuals with cognitive impairment. The 18-week intervention was relatively short, and the study did not establish whether the observed cognitive changes persist. Dietary intake was not strictly controlled, and genetic background and several lifestyle factors were not comprehensively assessed, leaving potential residual confounding. Immune assessment was limited primarily to NK cell activation, and the mechanisms underlying the differing effects of the two mushroom strains remain unclear.

Daily consumption of bread containing 50 g of maitake mushroom strain Y10M for 18 weeks was associated with improvements in MoCA-J scores and increased NK cell activation in healthy older Japanese adults. The findings suggest that the Y10M strain of maitake mushroom may help support cognitive health in healthy older adults. However, confirmation in larger and longer-duration clinical trials is needed, and the underlying mechanisms remain to be clarified. However, the lack of consistent benefits across cognitive tests and mushroom strains, together with the small sample size and short intervention duration, warrants confirmation in larger, longer-term clinical trials.

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Posted November 2, 2026.

Dr. Tabish Mehraj is a pharmaceutical scientist with expertise in pharmaceutics, drug delivery, and formulation development. She earned her PhD in Pharmaceutical Sciences from the University of Mississippi, where her research focused on the formulation, optimization, and characterization of lipid-based nanocarriers for targeted liver delivery of antimalarial therapeutics. Dr. Mehraj has also served as an ORISE Fellow at the U.S. Food and Drug Administration (FDA), where she evaluated the effects of formulation and process design on the quality and performance of intravaginal drug delivery systems and developed bio-relevant in vitro drug release testing methods. She has teaching experience in pharmaceutical and life sciences courses and has authored peer-reviewed publications, book chapters, and conference presentations. Dr. Mehraj is an active member of the American Association of Pharmaceutical Scientists and has been recognized by honor societies including Rho Chi and Gamma Beta Phi.

Reference:

1. Jogi, E. M., Kato, M. C., Masuda, Y., Konishi, M., Kuwabara, N., Sato, S., … & Hashimoto, M. (2026). Maitake Mushroom (Grifola frondosa) Enhances Cognitive Function in Healthy Older Japanese: A Randomized, Double-Blind, Placebo-Controlled Trial. Journal of Nutritional Science and Vitaminology, 72(2), 163-175.