January 27, 2015
Immune-modulating Effects of Maitake Mushroom Extract
Deng G, Lin H, Seidman A, et al. A phase I/II trial of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients: immunological effects. J Cancer Res Clin Oncol. 2009;135(9):1215-1221.
Phase I/II dose escalation trial
Thirty-four postmenopausal breast cancer patients (≥18 y) with resected stage I, II, or III breast cancer who were free of disease after initial treatment were enrolled sequentially in 5 cohorts.
Grifola frondosa (Maitake) liquid extract was taken orally at 0.1, 0.5, 1.5, 3, or 5 mg/kg twice daily for 3 weeks. Peripheral blood was collected at days −7, 0 (before the first dosing), 7, 14, and 21 for ex vivo analyses. The primary endpoints were safety and tolerability. In addition and of more interest, dose-response curves were calculated for 20 immunological endpoints.
Researchers found that oral administration of Maitake medicinal mushroom extract during a 3-week period is well tolerated. No dose-limiting toxicity was experienced up to 10 mg/kg per day. The intermediate dose (5-7 mg/kg per day) was associated with the most prominent functional changes, such as increased production of interleukin (IL)-2, IL-10, tumor necrosis factor-α and interferon-γ by subsets of T cells.
Another notable finding is that this agent appears to be associated with the production of both stimulatory (IL-2) and suppressive (IL-10) cytokines. This is contrary to the usual public perception that medicinal mushroom extracts boost immune function.
The clinical effect of the balance of these cytokines is unknown. In general, the immunological changes observed were moderate. No immunological parameters increased more than 100% from the pretreatment baseline.
Among the 20 immunological parameters, there was variability in the dose response curves: Some parameters showed a smooth decrease or increase in response to ascending doses of Maitake; others showed the greatest effect at an intermediate dose and less effect at higher dose. The variation in the shape of dose response curves illustrates that Maitake has a different influence on various aspects of the immune system, such as CD+ T cells and granulocytes.
This study illustrates the fact that the effects of botanical extracts are complex. Substances such as water-based extracts or ethanolic extracts or whole Maitake are considered immunostimulatory, but this study suggested mixed actions. The suppressive cytokines are involved with downregulating inflammatory responses. The meaning of these results are not entirely clear; more investigation is needed to see if these multiple actions of Maitake have an amphoteric (overall balancing) effect or in fact an adverse effect on those with certain low levels of cytokines. What this most clearly illustrates for practice is that we should not look at these substances clearly as immune upregulators. In many clinical conditions, we may want simultaneous decreases in inflammation and increased action of some defensive infection or tumor-fighting cytokines. As the authors point out, “immunomodulator” is perhaps a more appropriate term for this medicinal fungus than “immunostimulator.”
In this trial, no apparent clinical changes were observed, but the study was not designed to look for clinical efficacy endpoints. It is clearly a small sample size (34) that is divided into 5 groups. Nevertheless, as an in vivo study done on a patient population that often consumes immune-enhancing dietary supplements, the fact that the pharmacological actions and the dose-response curves are so variable from 1 extract and dose to another suggests further queries are necessary to see what the biological effects truly are.