Part 2 Edible Fungi & Exercise-Induced Immunosuppression - by Ricardo Adamo

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The ‘open window’ in stress-induced immunosuppression due to exercise may be beneficial to the athlete (5,18-21). Acute stress can induce a beneficial immune trafficking response, while chronic stress can induce a state in which certain cytokines are down-regulated and pro-inflammatory cytokines are up-regulated beyond the ‘open window’ (5,9).

An athlete who presents with long-term weakened cellular immunity, and longer recovery times and abnormalities in metabolic functions, may have functionally impaired performance and/or recovery that could even equate to chronic fatigue syndrome (CFS) (5,18-21). Excessive effort also requires increased metabolism, which at a cellular level, can be pathological, protective or regulatory depending on the stress response to the exercise, environment and length of time (18-21). However, some of the underlying cellular responses are well-maintained, which may assist with targeted therapeutic strategies if metabolic states can be recognised by known underlying metabolites (Figure 1 in Part 1) (2,18-21).

Factors such as adenosine depletion play a role in stress-induced immunosuppression. Glutamine is one of many currencies to these signal transduction pathways, as growing mammalian cells use glutamine as a nitrogen source for TCA cycle metabolites. Reactions that replenish TCA cycle intermediates occur due to the breakdown of glutamine when glucose levels are too low to maintain TCA cycle energy production.

BCAAs, glutamine and glutamic acid are abundant in edible mushroom protein content and are needed for human physiological functions (6, 14). Therefore, once the tough chitinous cellular walls of fungi are broken down, they provide BCAAs to regulate mTOR-mediated protein, regulate and activate cytokines, and modulate the uptake of glutamine and glutamic acid for chitinase (enzyme) activation (6,12,13,16). If extracted, products are incorporated and β-glucans and secondary metabolites for immunomodulatory and immunostimulatory activity are then acquired (See Figure 4).

Fig 2 Part 2 mushroom

Figure 4 - Typical supplementation levels (11)

However, the quality of fungi products is based on different measurements between species, powders vs extracts and fruit body vs mycelium-based products (Figures 4 and 5). There are no unambiguous rules to grade mushroom product quality. Mycelium is the actual living organism, while the fruit body is a reproductive structure that produces spores to continue the life cycle (Figure 3 in Part 1). Cultivating mushrooms commercially is difficult. Medicinal species are even more complex. Some species take up to three months to harvest and have a range of quality measurements, scaling to genomics-assisted breeding.

The extractions and methods used are what set the bioactivity of the final product apart (15, 16). β-glucan can exist as polysaccharide-protein complexes, having an assortment of proteins and sugars that are needed to fully activate immune cascades (4,15). Ethanol extraction is needed to obtain most of these protein compounds. The inhibitory and antioxidant activities can be significantly lower in hot-water extracts than cold-water extracts (6,17). Cold-water extraction before hot-water or ethanol extraction can yield higher antioxidant and inhibitory activity stronger than in singular extracts (16, 17). For other immunomodulatory compounds in fungi, see Figure 5. An under-recognised measurement of mushroom extractions in all species is nucleoside content, as this gives edible fungi their distinct umami (savoury taste) flavour (13).

To conclude, although the difference in bio-active ingredients mean that characterising product quality is not a singular reference or microparticulate aspect of β-glucan percentage, nucleotide content, or phenolic activity, these provide certainty to the practitioner/consumer. What matters in this rapidly growing industry is a company’s product acquisition or development methods. Due to the lack of regulation, it is essential to know your supplier and the methods they use when assessing the quality and safety of consumption of mushrooms and related products.

Note: As some fungi display an incredible ability to bio-remediate (process used to treat contaminated media such as heavy metals/toxic molecules), finding 100% organic products is crucial.

Figure mushroom blog 2

Figure 5 - The mushroom life cycle

References (continued from Part 1):

  1. Geng P et al (2017). Antifatigue Functions and Mechanisms of Edible and Medicinal Mushrooms. Biomed Res Int. 2017: 9648496.
  2. Phan CW et al (2017). A review on the nucleic acid constituents in mushrooms: nucleobases, nucleosides, and nucleotides. Critical Reviews in Biotechnology.
  3. Hoxhaj G (2017). The mTORC1 signaling network senses changes in cellular purine nucleotide levels. Cell Rep. 21(5):1331–1346.
  4. Elder M et al (2017). β-Glucan Size Controls Dectin-1-Mediated Immune Responses in Human Dendritic Cells by Regulating IL-1β Production. Front Immunol. 8:791.
  5. Zhu F et al (2015). Beta-glucans from edible and medicinal mushrooms: Characteristics, physicochemical and biological activities. Journal of Food Composition and Analysis. 41:165-173.
  6. Chen P et al (2016). Extraction temperature affects the activities of antioxidation, carbohydrate-digestion enzymes, and angiotensin-converting enzyme of Pleurotuscitrinopileatus extract. Journal of Food and Drug Analysis. 24(3):548-555. [online].
  7. Campbell J & Turner J (2018). Debunking the Myth of Exercise-Induced Immune Suppression: Redefining the Impact of Exercise on Immunological Health Across the Lifespan. Front Immunol. 9:648.
  8. Naviauz R et al (2017). Metabolic features of chronic fatigue syndrome. PNAS. 113(37):E5472-E5480.
  9. Vogt H et al (2016).Metabolic features of chronic fatigue syndrome revisited. Proc Natl Acad Sci U S A. 113(46):E7140-E7141.
  10. Naviaux R et al (2016). Reply to Vogt et al: Metabolomics and chronic fatigue syndrome. Proc Natl Acad Sci U S A. 113(46):E7142-E7143.