Food as medicine; white button mushroom; agaricus bisporus; super food; beta-glucans; immune modulatory, antioxidant; anti-inflammatory, anti-cancer, anti-diabetic, anti-hyperlipidemic.

1. FOOD AS MEDICINE:
WHITE BUTTON MUSHROOM
AGARICUS BISPORUS
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 Dec. 2018

2. Lecture Outline
▪ Milestones in white button mushroom culture.
▪ Scientific classification of white button mushroom: Agaricus bisporus
▪ Global production and consumption of button mushroom in US.
▪ Anatomy and life cycle of button mushrooms.
▪ Nutritional and medicinal properties of white button mushroom.
▪ Immune-modulation and anti-inflammation.
▪ In vitro, animal and human studies of bioactive compounds of button mushroom.
▪ Controversy over mutagenic agaritine.
▪ Summary.

3. Number of publications on Agaricus Bisporus (Button Mushroom)
in PubMed from 1960 – 2017
https://www.ncbi.nlm.nih.gov/pubmed/?term=agaricus+bisporus

4. Milestones in Cultivation of Buttton Mushroom (Agaricus bisporus)
White button mushroom
Shiitake mushroom
Enokitake mushroom
Chinese black mushroom

5. Meaning of Agaricus bisporus: white button mushroom and
microscopic images
▪ Agaricus means gilled mushroom
▪ Bisporus refers to the two-spored basidia lining the gills

6. World population (billion) vs. total world
Mushroom production (billion kg)
http://www.wsmbmp.org/1/01.pdf

7. World population (billion) vs. total world
Mushroom production (billion kg)
Estimated production of Agaricus bisporus in
selected countries in 2010
http://www.wsmbmp.org/1/01.pdf

8. Top Mushroom Consuming Countries in the World (2015)

9. 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

10. What do Button, Cremimi and Portobello mushroom
have in common?
White button
Cremimi
Portobello
Agaricus bisporus

11. Modern Taxonomy and Classification of white button mushroom:
Agaricus bisporus
AAG
https://slideplayer.com/slide/10578130/
Agaricus bisporus

12. Anatomy of white button mushroom:
agaricus bisporus
http://mrtbiologyclass.blogspot.com/2013/11/basidiomycetes-fungal-fruiting-body.html

13. White mushroom and Portobello Mushrooms of
Species Agaricus bisporus
http://bio.pisceswebdesign.com/species/agaricus-bisporus
white button mushrooms portobello mushrooms spore forming gills

14. Microscopic images of spores of white button mushroom:
Agaricus bisporus
https://www.youtube.com/watch?reload=9&v=tUjBv8WUEso
mushroom gills spores on gills two spores attached to gills

15. Life cycle of Agaricus bisporus
https://www.researchgate.net/publication/289984781

16. Composition of Nutrients in Fresh White Button Mushroom:
Agaricus bisporus
Macronutrients
g/100g
Micronutrients: minerals
mg/100g
Micronutrients: vitamins
mg/100g
adapted from J Nat Sci Med 2018;1:4-9

17. Essential amino acids in white Button Mushroom:
Total protein in fresh mushroom is 3 g/100g

18. Fatty Acids in white button mushroom
Total lipids 2.7 mg/100 g dry weight
https://content.sciendo.com/view/journals/pjfns/67/3/article-p173.xml

19. Bioactive compounds of white button mushroom:
agaricus bisporus
Bioactive compounds
▪ Polysacharrides: (1,6), (1,4)-linked α-glucan----------- 20.4%
(1,6)-linked Ᏸ-glucan------------------------23.7%
mannogalactan e.g. fucogalactan--55.8%
▪ Phenolic compounds (e.g. myricetin, caffeic acid)
▪ Ergothioneine (sulfur-containing amino acid)
▪ Indole compounds (e.g. serotonin, kynurenic acid)
▪ Lectins (carbohydrate binding proteins)
▪ Tyrosinase (enzyme for melanin synthesis)
▪ Lovastatin (HMG-CoA reductase inhibitor)
https://content.sciendo.com/view/journals/pjfns/67/3/article-p173.xml
Foods 2016, 5, 80; doi:10.3390/foods5040080
Ᏸ-glucan

20. Bioactive compounds of white button mushroom:
agaricus bisporus
Fresh mushroom contains Ᏸ-glucan 0.2 g/100g mushroom
Bioactive compounds Function
▪ Polysacharrides: (1,6), (1,4)-linked α-glucan----------- 20.4% energy metabolism
(1,6)-linked Ᏸ-glucan------------------------23.7% immuno-modulatory
mannogalactan e.g. fucogalactan--55.8% anti-inflammatory
▪ Phenolic compounds (e.g. myricetin, caffeic acid) antioxidant
▪ Ergothioneine (sulfur-containing amino acid) antioxidant
▪ Indole compounds (e.g. serotonin, kynurenic acid) intracellular signaling
▪ Lectins (carbohydrate binding proteins) intracellular signaling
▪ Tyrosinase (enzyme for melanin synthesis) protein synthesis
▪ Lovastatin (HMG-CoA reductase inhibitor) anti-cholesterol synthesis
https://content.sciendo.com/view/journals/pjfns/67/3/article-p173.xml
Foods 2016, 5, 80; doi:10.3390/foods5040080

21. Nutritional and medicinal benefits of white button mushroom:
Summary
Medicinal
bioactives
ODA=10-oxo-trans-8-decenoic acid
Nutrient
Benefit Compound
Adapted from https://content.sciendo.com/view/journals/pjfns/67/3/article-p173.xml

22. Immune modulation:
Components of the immune system
system
• Immune system
organs
• Primary organs
• Secondary organs
cells
• Inborn immunity
• Acquired immunity

23. Components of the immune system

24. The components of the immune system
Cell derived and plasma derived mediators
24

25. Components of the immune system

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

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

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

29. The Immune-Enhancing Benefits of Beta Glucans
▪ beta glucans act as immunomodulator agents, meaning they trigger a cascade of
events that help regulate the immune system, making it more efficient.
▪ beta glucans stimulate the activity of macrophages, which are versatile immune cells
that ingest and demolish invading pathogens and stimulate other immune cells to
attack.
▪ Macrophages also release cytokines, chemicals that when secreted enable the
immune cells to communicate with one another.
▪ In addition, beta glucans stimulate lethal white blood cells (lymphocytes) that bind
to tumors or viruses, and release chemicals to destroy it.
https://www.lifeextension.com/magazine/2009/12/the-immune-enhancing-benefits-of-beta-glucans/page-01

30. 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

31. β-glucan is one of the key components of the mushroom cell wall
https://www.researchgate.net/publication/26281450_The_effects_of_-glucan_on_human_immune_and_cancer_cells

32. β-glucan is one of the key components of the fungal cell wall
https://www.researchgate.net/publication/26281450_The_effects_of_-glucan_on_human_immune_and_cancer_cells

33. 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

34. 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.
https://www.sciencedirect.com/topics/food-science/glucans
ROS=reactive oxygen species
NO=nitric oxide

35. Immuno-modulatory actions of button mushrooms
Button mushrooms strengthen the immune system by enhancing the
• actions of White blood cells: ▪ Neutrophils
▪ Macrophages
▪ NK cells
• and reducing the release of inflammatory cytokines e.g.
▪ TNF-α
▪ iL-1Ᏸ
Inflammation
Phagocytosis Lysis

36. Phagocytosis of bacteria by a Neutrophil
https://www.researchgate.net/figure/Phagocytosis

37. NK cell-initiated immune responses are sustained by T cells
https://www.immunooncologyhcp.bmsinformation.com/antitumor-immunity/pathways/SLAMF7-pathway

39. Pain Swelling Heat Redness
The body’s immune response to tissue injury

40. Mechanism of inflammation: chemical mediators
Release of preformed mediators
Newly synthesized mediators
Phospholipase A₂
Inducible COX-2
Inducible 5-LOX

41. Actions of inflammatory chemical mediators

42. Timeline of Inborn (innate) and Acquired (adaptive) immunity
http://pharmrev.aspetjournals.org/content/66/1/80
Inborn immunity Acquired immunity
insect sting
rheumatoid arthritis
Time

43. How drugs or chemical mediators work?
https://hubpages.com/education/How-drugs-act-tyrosine-kinase-receptors-hormone-receptors

44. Mechanism of receptor blockade
Antagonist (drug)
Agonist (chemical mediator)
receptor
response No response
cell membrane
cell membrane

45. Mechanism of Anti-inflammation by Ᏸ-glucans
steroids
Aspirin; NSAIDS; Ᏸ-glucans
*zileuton
*=discontinued 2008 Thromboxane synthase inhibitor
Receptor blocker
?

46. β-glucan is one of the key components of the fungal cell wall
https://www.researchgate.net/publication/26281450_The_effects_of_-glucan_on_human_immune_and_cancer_cells

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

48. Effect of 1,3/1,6 Beta-glucan on NK cells in humans for 3 months
Adapted from http://slideplayer.com/slide/4371502/
increaseinNKcellactivity

49. White button mushroom (Agaricus bisporus) lowers blood glucose and
cholesterol levels in diabetic and hypercholesterolemic rats (2009)
•Plasma glucose, TC, TG, and liver enzyme (ALT/AST) levels in diabetic rats.
•Nondiabetic (normal) and STZ-induced diabetic rats (control)
were fed saline and diabetic rats were fed saline with ABP (200 mg/kg BW) daily for 3 weeks.
•Plasma glucose, TC, and TG (A) and ALT and AST (B) levels were measured using commercial
kits after the 3-week feeding period.
•Each value on the figure represents means ± SEM of 6 rats.
•Comparisons between groups were performed by 1-way analysis of variance. Means for
each variable with no common letters differ (P b .05).
http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.472.3619&rep=rep1&type=pdf
ABP=A. bisporus powder
Glucose, cholesterol, triglycerides Liver enzymes

50. Cholesterol lowering effect of Lovastatin
Lovastatin

51. Polysaccharides from Agaricus bisporus and Agaricus brasiliensis show
similarities in their structures and their immunomodulatory effects on
human monocytic THP-1 cells
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158557/
Negative control (PBS)
positive control (LPS)
A. bisporus extract (ABS),
B. α-amylase treated A. bisporus extract (ABSE)
C. A. blazei extract (ABL).

52. Bioactive compounds/extracts from edible
mushroom with analgesic effect
Wang H, Liu Y, Han C. The analgesic effect of several edible mushrooms. OA Alternative Medicine
2013 Oct 01;1(3):22.

53. Anti-inflammatory and anti-nociceptive properties of the fucogalactans
EPF-Ab and EPF-Ah from Agaricus muschrooms
Anti-inflammatory and anti-nociceptive
fucogalactans
EPF-Ab (Mw =19.4 x 10³ g/mol)
EPF-Ah (Mw= 31.1 x 10² g/mol)
Wang H, Liu Y, Han C. The analgesic effect of several edible mushrooms. OA Alternative Medicine
2013 Oct 01;1(3):22.
Agaricus brasiliensis
A. bisporus var. hortensis

54. α-Amylase inhibitory activity of polysaccharides from A. bisporus:
in vitro study using pancreatic α-amylase
https://scialert.net/fulltext/?doi=rjphyto.2018.14.20
(acarbose)

55. Anti-Cancer Activity of Phytochemicals in White Button
Mushrooms (Agaricus bisporus) 2006
Samples treated with 10× mushroom extract
(total 10×) and aqueous extract (Aq) mushroom
MA, myristic acid; PA, palmitic acid; SA, stearic acid;
OA, oleic acid; LA, linoleic acid; LN, linolenic acid. *,
fatty acids
mushroom extract (total 10×)
and aqueous extract (Aq)
https://www.ncbi.nlm.nih.gov/pubmed/17178902

56. Mechanism of action of Anti-cancer compound in
white mushrooms: Aromatase Inhibitors
https://www.researchgate.net/figure/Mechanism-of-action-of-Aromatase-Inhibitor
Mushroom Fatty acids

57. The effect of replacing 20% of high-energy lean ground beef in the diet
with 20% of low-energy ground white button mushrooms
http://www.mdpi.com/2304-8158/5/4/80/htm
A mushroom-containing reduced calorie meal served over 4 days did not negatively affect satiety. Adapted from Cheskin, et al.

58. Weight loss diet substituting white button mushrooms for beef
with no change in caloric content (2016).
http://www.mdpi.com/2304-8158/5/4/80/htm
Weight loss phase
0-6 months
Maintenance phase
(after 1 year)
Additional blood factors
after weight loss phase
Weight loss diet substituting white button mushrooms for beef
with no change in caloric content. Based on data from Poddar, et al

59. Eating mushrooms daily may cut breast cancer risk by two thirds
▪ Scientists found that women consuming at least a third of an ounce of fresh
mushrooms every day were 64 per cent less likely to develop a tumour.
▪ Dried mushrooms had a slightly less protective effect, reducing the risk by around
half.
▪ The study, carried out in China, also showed women who combined a mushroom
diet with regular consumption of green tea saw an even greater benefit. The risk
among women in this group was reduced by almost 90 per cent.
▪ Some evidence suggests mushrooms act in a similar way to breast cancer drugs
called aromatose inhibitors, which blocks the body's production of the hormone
oestrogen, which can encourage the development of cancer
https://www.telegraph.co.uk/news/health/news/5000582/Eating-
mushrooms-daily-may-cut-breast-cancer-risk-by-two-thirds.html

60. Reduction of breast cancer risk by white button mushroom
Agaricus bisporus
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0104-42302017000400371
button mushroom button mushroom

61. Dietary Mushroom Intake May Reduce the Risk of Breast Cancer:
Evidence from a Meta-Analysis of Observational Studies (2014)
• The results from this meta-analysis
suggested that greater edible mushroom
consumption may be associated with a
lower risk of breast cancer.
• The research provided a perspective that
oral administration of mushrooms perhaps
contribute to breast cancer primary
prevention.
• However, available data are still sparse, the
findings need to be updated and confirmed
with well-designed prospective studies in
future.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972098/

62. Putative pathways of the bioactivation of agaritine in
white button raw mushroom
Adapted from https://www.researchgate.net/publication/13943221
(mutagenic)
(weakly mutagenic)

63. Influence of storage and household processing on the
agaritine content of Agaricus mushrooms
https://www.slideshare.net/SUZANNEVENEZIAITALY/hydrazinearticletousda
76
12
52
35
0
10
20
30
40
50
60
70
80
Drying Boiling Deep frying microwave heat
%agaritineremaininginmushroom

64. Controversy on button mushroom safety
▪ Currently available evidence indicates that the consumption of A. bisporus
mushrooms poses no toxicologic risk to humans.
▪ Fresh mushrooms contain 2-5 µg agaritine/g fresh weight, an aromatic hydrazine-
derivative mycotoxin.
▪ High amounts of chemically synthesized and chemically modified hydrazine
compounds, including agaritine, were reported to have carcinogenic effects in mice.
▪ However, these effect could not be replicated in a later study.
▪ Review of these studies by others concluded that the studies were not performed in
accordance with approved protocols for carcinogenicity studies, such as those
outlined by the International Conference on Harmonization.
The Journal of Nutrition
Supplement: Mushrooms and Health Summit Proceedings

65. Some delicious white mushroom cuisine

66. Summary
▪ Agaricus bisporus, the edible white button mushroom is a super food because of its
nutritional values and bioactive compounds.
▪ The button mushroom is low in calories but rich in essential amino acids, minerals
and fiber.
▪ The bioactive compounds are immuno-modulatory, antioxidant, anti-inflammatory,
anti-cancer, anti-microbial, anti-hyperglycemic and anti-hyperlipidemic.
▪ The mycotoxin hydrazine and its metabolites are carcinogenic in mice. However, the
results could not be replicated in later studies.

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