A scientific first: Reishi-Shiitake-Maitake combination has synergistic immune benefits

By Stephen Daniells

- Last updated on GMT

The product tested contained a combination of Reishi (pictured above), Shiitake, and Maitake mushroom extracts.  Image © Getty Images / Songsak Paname
The product tested contained a combination of Reishi (pictured above), Shiitake, and Maitake mushroom extracts. Image © Getty Images / Songsak Paname

Related tags mushrooms reishi Shiitake Maitake immune function

A combination of Reishi, Shiitake, and Maitake mushroom extracts may synergistically stimulate immune cells responses, says a new study from Australia.

The study describes – for the first time – that while individual extracts from the three mushrooms increased levels of cytokines involved in immune stimulation, the combination produced a far greater effect on cytokine expression than could have been predicted based on the effects of the individual mushrooms.

“A synergistic formula with a specific ratio of Maitake, Reishi and Shiitake mushroom extracts provides an increase in immune stimulation compared to the additive effect of the three individual extracts,” ​said the study’s lead researcher, associate professor Joe Tiralongo from Griffith University’s Institute for Glycomics.

“This now forms the basis for further studies focussed on elucidating the exact nature of this synergistic effect and potentially identifying additional synergistic formulations based on mushroom beta-glucans.”

The work was performed by researchers at Griffith University in Australia, in collaboration with scientists from Integria Healthcare, which also sponsored the study. Integria Healthcare and MediHerb was named as the 2015 winner of the American Botanical Council’s Varro E. Tyler Commercial Investment in Phytomedical Research Award​.

The Maitake:Reishi:Shiitake formulation analyzed in this study resulted in the development of MediHerb Mushroom Forte, ​a patent-pending product currently available in Australia and New Zealand via the practitioner product. While MediHerb products are distributed in the US by Wisconsin-based Standard Process, the synergistic mushroom product is not yet available in the US.

Study details

Tiralongo and his co-workers analyzed nine commercially available preparations from three mushroom species: Reishi (Ganoderma lucidum​), Shiitake (Lentinula edodes​) and Maitake (Grifola frondosa​), for beta-glucan and alpha-glucan content, and based on these data, combined three extracts into a formula.

Testing the extract individually or in combination on the expression of certain cytokines (small proteins excreted by immune cells important in cell signaling) in human white blood cells revealed that all extracts were potent immuno-stimulators. 

The combination was much more potent than the individual extracts, suggesting a synergistic effect, they reported.

“Even though synergistic immunomodulatory effects between plant natural products have been reported, to our knowledge this is the first report of synergistic immunomodulatory activity between defined mushroom preparations,”​ wrote the researchers in the journal PLoS One​.

“Specifically, this study revealed the first observation of a synergistic effect of a mushroom formula on the expression of the IL1-alpha, IL-6 and TNF-alpha, and an antagonistic effect on the expression of IL-10.”

Hans Wohlmuth, PhD, head of R&D at Integria and co-author on the new paper, told NutraIngredients-USA that Integria is continuing to collaborate with Griffith University on this. “We have recently applied for a large government grant to continue work on medicinal mushrooms. This would expand the work to look at other species and gain a better understanding of the structural requirements for beta-glucans to exert immune stimulating activity,”​ Dr Wohlmuth told us.

“We have recently completed a very small in-house pilot trial in humans. It won’t be published but it did yield some interesting results. A larger clinical trial may be on cards for later,” ​he added.


Commenting in a press release from Griffith University, Professor Mark von Itzstein AO, Founder and Director of the Institute for Glycomics, said the results were impressive.

“This is an excellent example of academia and industry working together to generate outcomes that not only inform the scientific community but importantly the general public who consume these products,”​ he said.

Source: PLoS One
Published online, doi: 10.1371/journal.pone.0224740
“Synergistic immuno-modulatory activity in human macrophages of a medicinal mushroom formulation consisting of Reishi, Shiitake and Maitake”
Authors: B. Mallard, D.N. Leach, H. Wohlmuth, J. Tiralongo

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