Food as medicine, maitake mushroom, grifola frondosa,composition, nutrient and medicinal properties, immune system, maitake MD fraction, maitake SX fraction,antihyperglycemic, antilipidemic, anticancer, umami flavor.

1. MAITAKE MUSHROOM
GRIFOLA FRONDOSA
HEN OF THE WOODS
By
Kevin KF Ng, MD, PhD
Former Associate Professor of Medicine
Division of Clinical Pharmacology
University of Miami, Miami, FL. USA
Email: kevinng68@gmail.com
A slide presentation for HealthCare Provider Seminar Jan 2019

2. Lecture Outline
▪ History of maitake (Grifola frondosa) mushroom culture.
▪ Scientific classification of maitake mushroom.
▪ Sales of mushrooms in US.
▪ Anatomy and life cycle of maitake mushrooms.
▪ Nutritional and medicinal properties of maitake mushrooms.
▪ Health benefits of maitake mushrooms.
▪ In vitro, animal and human studies of MD and SX fractions of maitake mushrooms.
▪ Flavor of maitake mushrooms; delicious cuisines.
▪ Summary

3. History of Maitake mushroom (Grifola frondosa) culture

4. Scientific classification of maitake mushroom

5. Category share of mushrooms sales in the United States in
2018, by mushroom type
https://www.statista.com/statistics/191390/fresh-mushroom-category-share-in-2011/
Button
Maitake

6. What is Maitake (Grifola frondosa) mushroom?
▪ Maitake (Grifola frondosa) is the Japanese name for an
edible fungus with a large fruiting body characterized by
overlapping caps.
▪ In Japanese, mai means dance and take means mushroom,
thus “dancing mushroom.”

7. What is Grifola frondosa ?
The scientific name Grifola frondosa is
derived from :
• griffin, the beast from Greek
mythology with the head and wings of an
eagle and the body of a lion and
• frondosa, meaning leaflike.

8. Other popular names of Maitake Mushroom
▪ Champignon Dansant
▪ Champignon Maitake
▪ Dancing Mushroom
▪ Hen Of The Woods
▪ Hongo Maitake
▪ King Of Mushrooms
▪ Monkey's Bench
▪ Ram's Head
▪ Sheep's Head
▪ Shelf Fungi

9. Native Habitat of the Maitake Mushroom
▪ In the wild, maitake grows on the base of oak
trees.
▪ It is native to the forests of northern regions in
North America, Europe, and Asia.
▪ Maitake grows from small spores, but expand in
size over time. A single maitake is able to grow up
to 100 pounds!
▪ In nature, maitake is found in the fall from
September through October.

10. Anatomy and life cycle of a mushroom
https://www.pinterest.com/pin/227431849908632708/?lp=true

11. Structure of a mushroom cell wall
Adapted from https://www.sciencedirect.com/science/article/pii/S2405805X16300230
cytoplasm
nucleus
http://www.nammex.com/redefining-medicinal-mushrooms/

12. Nutrient composition in Maitake mushroom
Adapted from https://www.nutritionvalue.org/Mushrooms%2C_raw%2C_maitake_nutritional_value.html

13. Bioactive compounds in Maitake (Grifola frondosa) mushroom
▪ Many fractions have been prepared.
▪ 47 compounds have been isolated.
▪ 2 fractions have been widely studied:
• MD fraction
• SX fraction

14. Composition of MD fraction (β-glucans/polysaccharides) in
Maitake mushroom

15. Timeline of studies on the biological effects of Maitake:
Grifola frondosa polysaccharide (GFP).
http://www.discoverymedicine.com/Yanli-He/2018/04/grifola-frondosa-polysaccharide-antitumor-and-other-biological-
activity-studies-in-china/
SFDA=State FDA of China

16. Classification of Bioactive Compounds in Maitake mushroom:
47 had been isolated
only β-glucans are widely studied
Adapted from https://www.researchgate.net/publication/315775118_Polysaccharides_in_Grifola_frondosa_mushroom_and_their_health_promoting_properties_A_review

17. Pharmacological Effects of MD and SX Fractions of Maitake Ᏸ-glucans
Mol. Wt. 1,000,000 Daltons
Mol. wt. 20,000 Daltons

18. What is the Immune System?
system
• Immune system
organs
• Primary organs
• Secondary organs
cells
• Inborn immunity
• Acquired immunity

19. Components of the immune system

20. The components of the immune system:
Cell derived and plasma derived chemical mediators
20

21. Components of the immune system

22. Functions of the immune system:
Biologic response
Inflammation
Acute

23. Functions of the immune system
Inflammation
(Non-specific)
Specific inflammation
Acute

24. Timeline in evolution of
Inborn (innate) and Acquired (adaptive) immunity
Innate immunity adaptive immunity
specific inflammation
Non-specific

25. Functions of the Immune System
▪ Removal of dead cells by phagocytosis.
▪ Destruction of cancer cells by lysis.
▪ Generation and release of cytokines.
▪ Communication with immune cells.
▪ Protection from fungi, bacteria and virus

26. What is a polysaccharide?
▪ A long chain of carbohydrate consisting of a number of sugar
molecules bonded together, e.g. starch, cellulose or glycogen.
▪ The polysaccharide from maitake mushroom (grifola frondosa)
is called beta-glucan.
starch

27. What is a beta-glucan?
▪ Beta (Ᏸ) refers to the orientation of the linkage bond.
▪ Glucan molecule is a polysaccharide of D-glucose monomers, linked by glycosidic
bonds.
https://www.nutramunity.com/what-is-nutramunity/compare-beta-glucans/

28. What is a Beta-1, 3 and Beta-1,6 Glucan?
▪ Beta refers to the structural configuration of
the molecule.
▪ Glucan refers to a polysaccharide of D-glucose
monomers, linked by glycosidic bonds
▪ The number 1,3 and 1,6 refers to the glycosidic
linkage and bonding of the glucose molecule

29. Cellular and hormonal effects of β-Glucans on the
immune system
Adapted from Medicina (Kaunas) 2007; 43(8) and
https://jhoonline.biomedcentral.com/articles/10.1186/1756-8722-2-25

30. Absorption of soluble Ᏸ-glucans in the intestine
https://en.wikipedia.org/wiki/Peyer%27s_patch https://www.pinterest.com/pin/354165958170035412/https://vet.uga.edu/ivcvm/courses/vpat5215/
digestive/week04/diarrhea/diarr4.htm
30

31. Beta 1,3/1,6 Glucan and the immune system
https://www.action-inter.net/beta-1316-glucan-and-the-immune-system.html
31

32. The uptake and fate of
insoluble β-glucan on immune cells
https://openi.nlm.nih.gov/detailedresult.php?img=PMC2704234_1756-8722-2-25-2&req=4

33. Pharmacokinetics, pharmacodynamics and
bioavailability of Ᏸ-glucans
▪ The bioavailability of Ᏸ-glucans in humans has not been clearly established.
▪ Intravenously administered (1,3)-β-glucans have similar half-lives.
▪ 70% of (1,3)-β-glucans are deposited in the liver and spleen.
▪ Glucan derived from Grifola frondosa is reported to have a T1/2 of 6.4 h following
systemic administration in normal mice.
▪ In rabbits, intravenous administration of a 92-kDa radio labelled (1,3)-β-glucan
isolated from Candida albicans showed a distribution T1/2 of less than 5 min.
▪ Most of the radio labelled (1,3)-β-glucan (>97%) was associated with cell-free
plasma, while radioactivity associated with blood cells was initially found in platelets
and later (2 h) distributed to polymorphonuclear leukocytes and red blood cells.
https://www.sciencedirect.com/topics/immunology-and-microbiology/grifola-frondosa

34. Pharmacological Effects of MD and SX Fractions of Maitake Ᏸ-glucans
Mol. Wt. 1,000,000 Daltons
Mol. wt. 20,000 Daltons

35. Health benefits of maitake mushroom
grifola frondosa Polysaccharides
▪ Anti-cancer activity
▪ Immune regulation
▪ Liver protection
▪ Cardiovascular disease protection
▪ Anti-hyperglycemic
▪ Anti-hypertensive activity
▪ Anti-hyperlipidemic activity
▪ Anti-radiation activity
http://www.discoverymedicine.com/Yanli-He/2018/04/grifola-frondosa-
polysaccharide-antitumor-and-other-biological-activity-studies-in-china/

36. The structure of maitake D-fraction
http://www.discoverymedicine.com/Yanli He/files/2018/05/discovery_medicine_no_138_lijuan_zhang_figure_1.jpg.jhtml?id=2|attachment_6
Xyloglucan, (1-6)-β-D-glucan with
(1-3)-β-D-glucan side chains (MD fraction)

37. Conceptual model for the interaction between β-glucans and receptors of the
innate immune system (macrophages)
Interaction between Dectin-1 and toll-like receptors (TLRs) results in synergistic effects. ROS, reactive oxygen species.
https://www.sciencedirect.com/topics/food-science/glucans

38. The human beta-glucan receptor is widely expressed in
immune cells
▪ Monocyte
▪ Macrophage
▪ Dendritic cells
▪ Neutrophils
▪ Eosinophils
▪ B cells
▪ Subpopulation T cells
https://www.ncbi.nlm.nih.gov/pubmed/15816015
β-glucan

39. Effects of SX-fraction (SXF) on fasting blood glucose in
seven type 2 diabetic patients after 2-4 weeks
Adapted from https://www.researchgate.net/figure/Hypoglycemic-effects-of-SX-fraction-SXF-on-type-2-diabetic-patients-25_tbl1_315775118

40. Mechanism of action of SX-fraction from
Maitake mushroom
▪ SX-fraction has hypoglycemic activity in diabetic mice and type 2 patients.
▪ SX-fraction is a glycoprotein having a protein to saccharide ratio ranging from about 75:25 to
about 90:10; its average molecular weight is 20,000.
▪ The saccharide portion of SX-fraction was found to have Galactose, Mannose, Glucose, N-
acetylglucosamine and Fucose.
▪ Evidences suggested that SX-fraction target the insulin receptor and insulin receptor
substrate therein that trigger the subsequent signaling events.
▪ The hypoglycemic action of SX-fraction was associated with the activation of impaired insulin
signal transduction pathway, thereby ultimately facilitating glucose uptake.
▪ Clinical study showed that all seven diabetic patients demonstrated over 30% (30%–63%)
decline in their fasting blood Glucose levels under a SX-fraction regimen of 2–4 weeks.
https://www.researchgate.net/publication/315775118_Polysaccharides_in_Grifola_fr
ondosa_mushroom_and_their_health_promoting_properties_A_review

41. Effects of Grifola frondosa on serum lipid levels of rats
https://www.frontiersin.org/articles/10.3389/fmicb.2016.01186/full

42. Anti-angiogenesis effect of Maitake Pro 4x on blood vessel
density in breast tumor in mice
https://www.researchgate.net/publication/305213822_Maitake_Pro4X_has_anti-
cancer_activity_and_prevents_oncogenesis_in_BALBc_mice

43. Inhibition of liver metastasis in mice after 30 days of treatment
with Maitake D-fraction (2001)
http://archive.foundationalmedicinereview.com/publications/6/1/48.pdf

44. Beta-Glucans Derived from D-Fraction of Maitake (Grifola frondosa)
Mushroom prevent Mammary Carcinogenesis in mice
https://www.intechopen.com/books/breast-cancer-from-biology-to-medicine/immunotherapeutic-
and-preventive-role-of-purified-extract-rich-in-beta-glucans-derived-from-d-fraction

45. Reduction of Chemotherapeutic Side-Effects by
D-Fraction (n=455).
http://archive.foundationalmedicinereview.com/publications/6/1/48.pdf

46. Summary of Actions of maitake mushroom D-fraction
▪ The auseful parts of maitake mushroom are the fruiting body and mycelium. Maitake
mushroom contains beta-glucan, which has been shown to possess antitumor activity. The
"D-fraction" of beta-glucan appears to be the most active form.
▪ Maitake mushroom has immunostimulant effects and activates natural killer cells, cytotoxic
T-cells, interleukin-1, and superoxide anions.
▪ Preliminary research suggests that maitake mushroom can prevent metastasis of
experimentally induced tumors as well as prevent tumor occurrence in normal cells.
▪ Researchers are particularly interested in maitake mushroom and its extracts because they
appear to be active orally. Other research suggests that maitake mushroom can lower blood
pressureand improve the lipid profile in experimental hyperlipidemia.
▪ Polysaccharides from the fruiting bodies in maitake mushroom also appear to have a
hypoglycemic effect, possibly by activating insulin receptors. Since insulin resistance occurs
in women with polycystic ovary syndrome (PCOS), there is also interest in using maitake
mushroom for PCOS.
http://naturaldatabase.therapeuticresearch.com/(X(1)S(l3j1ybyyg15t1k45mgwiwiyl))/nd/PrintVersion.aspx?id=560&AspxAutoDetectCookieSu
pport=1

47. Maitake MD-Fraction on cancer patients : Literature Review (2002)
▪ Maitake mushroom (Grifola frondosa) MD-fraction containing beta-1,6 glucan with
beta-1,3 branched chains has anticancer property.
▪ A combination of MD-fraction and whole maitake powder was investigated to
determine its effectiveness for 22- to 57-year-old cancer patients in stages II-IV.
▪ Cancer regression or significant symptom improvement was observed in 58.3
percent of liver cancer patients, 68.8 percent of breast cancer patients, and 62.5
percent of lung cancer patients.
▪ The trial found less than 10-20 percent improvement for leukemia, stomach cancer,
and brain cancer patients.
▪ When maitake was taken in addition to chemotherapy, immune-competent cell
activities were enhanced 1.2-1.4 times, compared with chemotherapy alone.
▪ Animal studies supported the use of maitake MD-fraction for cancer.
https://www.researchgate.net/publication/11253855_Maitake_MD-Fraction_aid_cancer_patients

48. Review of efficacy of Maitake Mushroom (Grifola frondosa) by the
Natural Standard Research Collaboration using the level of evidence grade (2009):
Evidence Grade Source
▪ A (strong scientific evidence) ▪10 data bases
▪ B (good scientific evidence) ▪20 additional journals
▪ C (unclear or conflicting scientific evidence) ▪50 secondary references
▪ D (fair negative scientific evidence)
▪ F (strong negative scientific evidence)
▪ Summaries of findings and grade of effectiveness of Maitake Mushroom:
Cancer C
Diabetes C
Immunostimulation C
▪ Conclusion: more research is needed.
https://www.researchgate.net/publication/26248013_Maitake_mushroom_Grifola_frondosa_Systematic_review_by_the_natural_standard_research_collaboration

49. Commercial products from Maitake (Grifla frondosa) mushroom
▪ Raw mushrooms
▪ Dried mushrooms
▪ Power extract
▪ Tincture extract
▪ Tablets
▪ Capsules

50. Flavor: equivalent umami concentration in mushrooms
umami=fifth taste
Adapted from https://www.researchgate.net/publication/240299750_The_Umami_Taste_of_Edible_and_Medicinal_Mushrooms

51. Some delicious maitake mushroom cuisine

52. Summary
▪ Maitake mushroom is scientifically known as Grifola frondosa.
▪ Its nutrient and medicinal properties are known from time immemorial.
▪ The high molecular weight polysaccharides have been widely studied in
the last 40 years.
▪ Known as β-glucans, the polysaccharides have been analyzed into fractions.
▪ MD-fraction has been found to have anti-cancer, immuno-modulatory
and anti-inflammatory properties.
▪ SX-fraction has been found to have anti-hyperglycemic property.
▪ The umami flavor of maitake makes it a highly sought after mushroom.

53. ANY QUESTION?
Please contact
Kevin KF Ng, MD, PhD
Email: kevinng68@gmail.com