Shiitake Mushrooms: Anti-Cancer, Anti-Aging, and More

Shiitake mushroom (Lentinus edodes), once little-known outside of East Asia, is a frequent sight these days in the produce section of Western supermarkets. While prized for its texture and flavor, it is shiitake’s health benefits that render this fungus priceless.

Why Supplement with Mushrooms?

“It is estimated that approximately 50% of the annual 5 million metric tons of cultivated edible mushrooms contain functional ‘nutraceutical’ or medicinal properties,” R. Chang noted in Nutrition Reviews. “In order of decreasing cultivated weight in tons, Lentinus (shiitake), Pleurotus (oyster), Auricularia (mu-err), Flammulina (enokitake), Tremella (yin-er), Hericium, and Grifola (maitake) mushrooms have various degrees of immunomodulatory, lipid-lowering, antitumor, and other beneficial or therapeutic health effects without any significant toxicity.”1

Shiitake has become a popular mushroom due to its smoky, savory taste and versatile texture. The recently confirmed benefits of this “Queen of Mushrooms” in mice and humans add evidence to centuries of traditional use. “Shiitake mushrooms are currently one of the five most cultivated edible mushrooms in the world,” note Kuo-Hsiung Lee and colleagues in the Journal of Traditional and Complementary Medicine. “They have been used medicinally and as healthy food for thousands of years in Japan, China, and Korea, and are now becoming popular in nutritional and medicinal products throughout Europe and North America.”24

The Health Benefits of Shiitake Mushrooms

In Advances in Applied Microbiology, S. C. Jong and J. M. Birmingham mention that “The shiitake mushroom is the second most popular edible mushroom in the global market. The shiitake mushroom contains proteins, fats, carbohydrates, vitamins, and minerals. Hypolipidemic and antithrombotic substances have been identified; the nucleic acids induce interferon production.”2

Early research uncovered an ability of shiitake to lower blood cholesterol when added to the diet of rats.3 A study involving an essential oil of shiitake found an inhibitory effect against platelet aggregation, which the researchers involved in the study attributed to a sulfur-containing compound known as lenthionine.4 Other research uncovered an ability of shiitake to modulate adhesion molecule expression, indicating a potential protective effect against cardiovascular disease.5

Shiitake Mushroom is Beneficial for Oral Health

Fluid in which shiitake mycelium was cultured has shown an antimicrobial effect when pitted against Streptococcus pyogenes, Staphylococcus aureus and Bacillus megaterium.6Lenthionine was suggested as the component responsible for the effect.

In a comparison of shiitake extract to chlorohexidine (the active component in the leading gingivitis mouthwash), pathogenic bacteria were reduced by shiitake while bacteria associated with health were not affected. 7 In contrast, chlorhexidine’s effect on all varieties of oral bacteria evaluated was limited. Another experiment found that an extract of shiitake mushroom prevented or reduced the induction of gene expression of the periodontal pathogens Prevotella intermedia and Actinomyces naeslundii.8In a study that compared the effects of an oral rinse that contained shiitake extract to Listerine or water in human participants, shiitake was associated with less plaque and a decrease in specific oral pathogen counts in comparison with water and less gingival inflammation compared to water or Listerine.9 The authors of the report concluded that shiitake could prove beneficial in controlling dental caries and/or gingivitis/periodontitis. A randomized, double-blind trial of a rinse containing shiitake concluded that shiitake extract has anticariogenic potential.10

The Anticancer Properties of Shiitake Mushroom

One of shiitake’s most promising areas of use is in cancer therapy. In two human breast carcinoma cell lines and two myeloma cell lines, an ethyl acetate fraction of shiitake induced apoptosis (programmed cell death) in 50% of the population of the tumor cell lines, whereas nonmalignant cells exhibited less sensitivity to the fungus.11 The authors of the report suggest that apoptosis may be the reason for shiitake’s growth-inhibitory effect in tumor cells. In another study, water extracts of shiitake inhibited the proliferation of a breast adenocarcinoma cell line and demonstrated an immunostimulatory effect in rat thymocytes.12

In addition to enhanced immunity, antitumor mechanisms of newly identified shiitake polysaccharides SLNT1, SLNT2, JLNT1, JLNT2, and JLNT3 include a tumoricidal effect and the induction of apoptosis.13

The immune-enhancing effect of shiitake was explored in a study in which MPSSS, a polysaccharide derived from the fungus, was administered to myeloid-derived suppressor cells, which inhibit T cell activity and promote tumor growth.14 Researchers demonstrated that MPSSS reversed immunosuppressive functions of myeloid-derived suppressor cells. Treatment with the compound also inhibited the growth of tumor cells in mice, which was correlated with a 38% lower percentage of myeloid-derived suppressor cells in the blood of treated animals compared to a control group.

In mice inoculated with lymphoma or human colon cancer cells, oral pretreatment with lentinan, a high molecular weight beta glucan isolated from shiitake, showed an antitumor effect.15 In another mouse study, animals injected with liver cancer cells and treated with the chemotherapy 5-fluorouracil (5-FU), the addition of polysaccharides derived from shiitake was associated with a greater reduction in tumor weight and volume than chemotherapy alone. This was accompanied by an increase in spleen and serum immune factors.16

In a study involving 8 patients with advanced gastrointestinal cancer who received a course of chemotherapy alone followed by a course of chemotherapy plus an extract of shiitake, 6 patients experienced chemotherapy-related adverse effects after the first course, but no adverse effects were reported following the second course that included shiitake.17

In a similar study, which included 7 patients undergoing postoperative chemotherapy to treat breast or gastrointestinal cancer or to prevent gastrointestinal cancer recurrence, quality of life and immune function improved following a second course of chemotherapy combined with shiitake extract, whereas an initial course of chemotherapy alone was associated with no changes.18 Among 10 patients who received 4 weeks of cancer immunotherapy followed by 4 weeks of immunotherapy plus shiitake mycelia extract, quality of life scores and immunity improved during the period in which shiitake was administered compared to the period in which the participants received immunotherapy alone.19

The Antiaging Potential of Shiitake Mushrooms

Research suggests that shiitake could have antiaging effects. In one study, shiitake mycelia zinc polysaccharides showed antioxidant activities in vitro and, in mice, upregulated total antioxidant capacity and the antioxidant enzymes glutathione peroxide and superoxide dismutase (SOD), and decreased malondialdehyde, a marker of oxidative stress.20 In a study involving aged mice, the heteropolysaccharide L2 from shiitake restored the aging-related decline in immune response and partially reversed the age-related alteration in intestinal microbiota.21 A study of aged mice inoculated with colon carcinoma found that pretreatment shiitake extract retarded tumor growth, which was accelerated in older mice compared to younger mice.22

The Bottom Line

Shiitake, commonly consumed as a food, appears to be safe when used medicinally by nonallergic individuals. A phase I trial that evaluated the effects of an extract of shiitake known as active hexose correlated compound (AHCC, which contains alpha-glucan and beta-glucan from shiitake mycelia) in healthy men and women found no significant laboratory parameter abnormalities and few adverse effects at a dose that was higher than that routinely used in humans, adding evidence to its safety.23

“As part of the Traditional Chinese Medicine and other folk medicine systems, many plant and fungal species are used as foods and dietary supplements to promote good health, as well as to prevent or treat many diseases,” they conclude. “Modern scientific methodology and medicinal chemistry approaches will continue to identify and evaluate the bioactive components found in Traditional Chinese Medicine prescriptions, and validate their use as sources of new, effective, and safe world-class new medicines and dietary supplements.”24

References

  1. Chang R. Nutr Rev. 1996 Nov;54(11 Pt 2):S91-3.
  2. Jong SC et al. Adv Appl Microbiol. 1993;39:153-84.
  3. Kaneda T et al. J Nutr. 1966 Dec;90(4):371-6.
  4. Shimada S et al. Biofactors. 2004;22(1-4):177-9.
  5. Martin KR. Nutr J. 2010 Jul 16;9:29.
  6. Hatvani N et al. Int J Antimicrob Agents. 2001 Jan;17(1):71-4.
  7. Ciric L et al. J Biomed Biotechnol. 2011;2011:507908.
  8. Canesi L et al. J Biomed Biotechnol. 2011;2011:230630.
  9. Signoretto C et al. J Biomed Biotechnol. 2011;2011:857987.
  10. Lingström P et al. J Biomed Biotechnol. 2012;2012:217164.
  11. Fang N et al. J Altern Complement Med. 2006 Mar;12(2):125-32.
  12. Israilides C et al. Phytomedicine. 2008 Jun;15(6-7):512-9.
  13. Wang KP et al. J Agric Food Chem. 2013 Oct 16;61(41):9849-58.
  14. Wu H et al. PLoS One. 2012;7(12):e51751.
  15. Ng ML et al. J Altern Complement Med. 2002 Oct;8(5):581-9.
  16. Ren M et al. J Tradit Chin Med. 2014 Jun;34(3):309-16.
  17. Okuna K et al. Asian Pac J Cancer Prev. 2011;12(7):1671-4.
  18. Yamaguchi Y et al. Am J Chin Med. 2011;39(3):451-9.
  19. Tanigawa K et al. Gan To Kagaku Ryoho. 2012 Nov;39(12):1779-81.
  20. Wang L et al. BMC Complement Altern Med. 2015 Apr 9;15:111.
  21. Xu X et al. Food Funct. 2015 Aug;6(8):2653-63.
  22. Ishikawa S et al. Cancer Immunol Immunother. 2016 Aug;65(8):961-72.
  23. Spierings EL et al. J Nutr Sci Vitaminol (Tokyo). 2007 Dec;53(6):536-9.
  24. Lee KH et al. J Tradit Complement Med. 2012 Apr-Jun; 2(2): 84–95.

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