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Medicinal Mushroom Preparations as Functional Food for Multiple
Sclerosis: A Review
Abstract
Multiple Sclerosis (MS) is a devastating autoimmune demyelinating disease of the central nervous system for
which there is no cure. Because the approved medications offer only a modest benefit, are very expensive,
and often have unbearable side-effects, many patients seek to influence the course of their disease using
diet, supplements, or unapproved therapies. Evidence indicating that edible mushrooms have great potential
to help maintain health and ameliorate illness is rapidly emerging. The scientific literature has been
reviewed; a few medicinal mushrooms are leading candidates for further MS research: species of the genus
Hericium, including Hericium erinaceus, species of the genus Cordyceps, including Cordyceps sinensis,
Cordyceps militaris, Cordyceps ophioglossoides, and Cordyceps pruinosa, Ganoderma species including
Ganoderma lucidum and Ganoderma tsugae, and Poria cocos. Not all medicinal mushrooms can be
recommended to those who suffer from MS; some may be detrimental to the MS patient by over-stimulating
the immune system. Impetuous consumption of any and all medicinal mushrooms is not advisable. A
scientific rationale exists for these species. The proposed mechanisms of actions are: the induction of
neurotrophic factors such as nerve growth factor (NGF), direct neurotrophic action of pharmacologically
active constituents, prevention of neuronal apoptosis, improvement in noradrenergic functioning in the locus
coeruleus system, catecholamine modulation, cholinergic action, cyclooxygenase (Cox-1/Cox-2) inhibition,
modulation of cytokine expression, competition with myelin autoantigens on immune cell receptor sites, nonsteroidal anti-inflammatory action, pro-steroidal endocrine modulation, antimicrobial action (viral and bacterial
microbes may contribute to Multiple Sclerosis manifestation as co-factors or even as the sole cause of MS[i]
[ii] [iii] [iv] [v]), sedative, analgesic and anti-nociceptive action, improvement in intestinal flora, improvements
in cardiovascular, hepatic, and renal functioning, antioxidant status, supplementation of conditionally
essential saccharides (CESs), and increasing the overall sense of health and well-being.
Skylar Saveland; David Porter, PhD; Edward Novey, MD; John Holliday, PhD
BioRevival, a Non-Profit Corporation, Marietta, GA
Poria cocos (Indian Tuckahoe)
Poriatin, derived from Poria cocos (Pc), reduced the severity of EAE.[i] Poria is commonly prescribed
in Asia for autoimmune diseases and is said to ameliorate these conditions by upregulating IL-10 and
suppressing Th-1 overactivity.[ii] Pc demonstrated significant immune-supressing activity in a heart
transplant model.[iii] Antioxidant activity suppressed free-radical-induced cytolysis.[iv] Poria markedly
inhibits HIV-1.[v] A traditional Asian preparation containing Pc reduced immune-mediated inflammation
in cultured astrocytes.[vi] Another Korean mixture containing Pc also displayed neuroprotective
effects[vii] and rescued neurons from nitric oxide induced damage, preventing the accumulation of
disability.[viii] A different traditional preparation of Pc and two other traditional Chinese medicines
demonstrated neuroprotective effects, in vitro and in vivo, reducing the production of NO and
preserving cognitive function in distinct animal models of neurological damage.[ix] Another mixture
containing P. cocos significantly inhibited cyclooxygenase-mediated inflammation.[x] Cyclooxygenase
(Cox-1/Cox-2) inflammation has recently been implicated in neurodegeneration.[xi] [xii] Traditional
Korean herbs used to protect the brain were screened to assess the different anti-cholinesterase
activities of each. P. cocos demonstrated 27.8% inhibition in the model.[xiii] Cholinergic intervention
has demonstrated great potential in the development of future MS therapeutics.[xiv] The reputed
ability of P. cocos to improve cognition was supported by another experimental model.[xv] Poria may
benefit individuals with MS through immune-modulation and multiple forms of neuro-protection.
Because of the pervasive use of alternative therapies by those who suffer from MS and marketing
campaigns promoting the use of preparations of questionable efficacy, an aggressive research program is
warranted, in order to further assess the potency of a medicinal mushroom preparation as a treatment for
Multiple Sclerosis. Anecdotal reports of significant relief of symptoms and relapses further indicate the need
for comprehensive scientific analysis.
Cordyceps sinensis, C. militaris, C. ophioglossoides, and C. pruinosa
Cordyceps sinensis (Cs) may be able to alter the course of various kinds of autoimmune diseases by
muting immune over-response to lipopolysaccharide (LPS).[i] Relapse in MS models can be induced by
introducing LPS into the spinal cord, causing an inflammatory cascade.[ii] [iii] Anti-inflammatory and
antinociceptive activities, and related antioxidant, anti-angiogenic, and nitric oxide (NO) inhibiting
activities of C. sinensis and C. militaris have been demonstrated.[iv] [v] Data show that Cs has been
effective in lupus models[vi] [vii] and human trials.[viii] Interferon-β, the reference drug for MS, may
benefit lupus patients, as well.[ix] Though marketed as an agent that can ‘boost’ immune response, Cs
has shown great potential for producing immunosuppressive agents[x] and possibly ameliorating
diseases like autoimmune nephropathy.[xi] Cs has potential as an immunoceutical for the treatment of
Th-1 mediated autoimmune diseases,[xii] of which MS is a member.[xiii]
Cs is widely used as a dietary supplement to increase strength and endurance. However, in competitive
male cyclists, no appreciable improvement was found.[xiv] Positive effects on endurance, fatigue and
objective stress measures have been recorded in experimental models.[xv] [xvi] In addition to increasing
endurance, researchers have noted an anti-inflammatory effect.[xvii] Researchers who assume the
clinical effectiveness of C. sinensis in relieving fatigue and increasing endurance, in the elderly, offer data
showing increases in hepatic adenosine triphosphate levels.[xviii] Many believe that C. sinensis may not
confer much benefit in increasing the strength and endurance of those who are near peak conditioning,
but greatly benefits the chronically fatigued.[xix] This belief is apparently supported by a randomized,
double-blind, placebo-controlled clinical trial that has not been published in English.[xx] Subjective
improvements in mood and energy are often felt by the consumer. Cs stimulates corticosteroid
production, in vitro,[xxi] and in vivo.[xxii] Corticosteroids, possessing substantial anti-inflammatory and
immunosuppressive activity, are approved for the treatment of relapsing/remitting MS. Production of
other endogenous steroids appears to be increased by Cs as well.[xxiii] The Cordyceps genus is a
known source of anti-viral,[xxiv] [xxv] antibacterial,[xxvi] and immune-modulating compounds that hold
promise for future discovery of therapeutic agents.[xxvii] Cyclosporine, the reference immunesuppressing drug for transplant surgery, is derived from the anamorph of C. subsessilis.[xxviii] The
potential beneficial actions of C. sinensis are immune-modulating, immune-suppressing, pro-steroidal,
non-steroidal anti-inflammatory, anti-oxidant, anti-fatigue, and anti-microbial. Improvement in hepatic and
renal functioning may also be of note.
Ganoderma lucidum (Reishi, Ling Zhi) & Ganoderma tsugae
Ganoderma lucidum (Gl) has been shown to inhibit forms of inflammation that are
implicated in MS such as inducible nitric oxide synthase (iNOS)[i] [ii] and histamine,[iii]
and has immune-modulating effects including the promotion of interleukin-10 (IL-10)
expression.[iv] IL-10 upregulation is an approach to MS and other autoimmune
conditions.[v] Ganoderma tsugae alleviated immune-mediated inflammation in an
allergic asthma model.[vi] A protein (LZ-8) from Gl suppressed autoimmune disease in
an animal model,[vii] showing extraordinary immunosuppressive potential comparable
to prednisolone and cyclosporine without toxic effects.[viii] Prednisone, a prednisolone
precursor, approved for use in remitting/relapsing MS because of the desired
immunosuppressive and anti-inflammatory action, has important side-effects. Gl
demonstrated neuroprotective potential by dramatically suppressing apoptosis of PC12
cells.[ix] Ganoderma species have unique immune-modulating, immune-suppressing
and neuroprotective potential that may be significant for MS treatment.
Cordyceps ophioglossoides (Co) prevented neuronal cell death in in vitro and in vivo models of amyloidbeta induced damage.[xxix] The role of amyloid in MS, damaging the actual axons and causing the
accumulation of disability, has been well described.[xxx] [xxxi] C. ophioglossoides also contains a novel
anti-fungal agent, ophiocordin.[xxxii] Co is not as well studied as other species of medicinal mushrooms.
Co may exert actions on many different systems. At this time, the proposed action of Co is neuro-specific
antioxidation, preventing amyloid-beta induced damage.
Hericium erinaceus (Yamabushitake, Hou Tou, Pom Pom, Lion’s Mane)
Hericium erinaceus (He) produces molecules, known as the erinacines, which have been shown to be
strong inducers of NGF, in vitro.[i] Intra-cerebral NGF infusion significantly reduced the manifestation of
experimental autoimmune encephalomyelitis (EAE) in a primate model.[ii] Erinacine A was confirmed as a
strong inducer of NGF, in vivo, with some specificity toward the locus coeruleus, a system that can further
neurotrophic activity, in a secondary manner, and induce other neurotrophic factors such as NT-3.
Interestingly, catecholamine production was significantly induced by the compound, indicating great
potential for the relief of Parkinson’s and other neurological disorders as well.[iii] The noradrenergic locus
coeruleus/lateral tegmentum system influences the functioning of large areas of the brain and spinal cord
and has been successfully targeted as a means to ameliorate Multiple Sclerosis.[iv] H. erinaceus extract
promoted myelination with no toxic effects, in vitro. Myelination was faster and began earlier than the
controls, while normal development was otherwise maintained.[v] An exo-polysaccharide, derived from
He, chemically unrelated to the erinacines, was found to promote adrenal neurite growth, differentiation,
and arborization more rapidly and with greater potency than brain-derived nerve factor (BDNF) or NGF.
Neuronal apoptosis was drastically reduced (from 50% to 20%) by the polymer, as well.[vi] Whole He
was found to be safe and effective against Alzheimer’s dementia in Japanese clinical trials.[vii]
A methanol extract of Cordyceps pruinosa inhibited important inflammatory mediators of Multiple
Sclerosis in vitro and in vivo: IL-β, TNF-α, NO, prostaglandin, Cox-2, and NF-κB.[xxxiii] This finding,
though preliminary and solitary, offers great hope for the future amelioration of Multiple Sclerosis.
Conclusions
Much remains to be learned about MS and future therapeutic interventions. There is
certainly reason to believe that dietary supplementation of these traditional products
can benefit the MS patient. However, further understanding of the active constituents,
optimum dosage, production styles, media construction, growth parameters, and the
distinct phases of the fungal lifecycle producing unique molecules is necessary to
ascertain whether ingesting a preparation of full-spectrum, unrefined natural product is
objectively and markedly useful in reducing the symptoms and inhibiting the
progression of Multiple Sclerosis. Second generation products such as extracts or
synthetic derivatives may prove advantageous.
Anti-microbial activities of He have been demonstrated. A novel laccase was isolated from He mushroom
with inhibitory activity toward HIV-1 reverse transcriptase.[viii] Herical, another derivative of He, inhibits a
large spectrum of bacteria and fungi.[ix] Cases of methicillin-resistant Staphylococcus aureus in humans
were cured during a Japanese clinical trial evaluating the merit of He as a therapeutic agent for
Alzheimer’s dementia. The anti-MRSA compounds were subsequently identified as two of the
erinacines.[x] In vitro, Hericium has a sedative effect on hippocampal neurons with no toxic effect,
apparently supporting the researcher’s view that H. erinaceus is promising for the treatment of diseases
such as MS, Alzheimer’s, etc.[xi] Erinacine E has been declared a kappa opioid agonist with analgesic
potential.[xii] Thus, the main proposed actions of Hericium erinaceus are neurotrophic, antiapoptotic,
adrenergic, catecholaminergic, antimicrobial, sedative and analgesic. Other beneficial effects may include
antioxidation, hepatoprotection, and immune-modulation. Hericium also contains important compounds
that incorporate xylose, galactose, fucose, and other CESs.
Photos courtesy of: Hericium erinaceus, David Porter; Cordyceps, clockwise from upper left: unremembered species, David Porter; C. ophioglossoides, Northwest Alliance for Computational Science and Engineering; C. militaris, [email protected]; C. pruinosa, Japanese Cordyceps Society; Ganoderma, David Porter; Ganoderma lucidum, George Barron; Poria cocos, David Porter; Cordyceps sinensis, special thanks to earthgrown.net.