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Sunday, April 3, 2016

Mega List: Is Cordyceps a safe and effective supplement?


DISCLAIMER: Cordyceps is classed as a nutrional supplement in the US and as such no research is required as to the safety or effectiveness of Cordyceps. USE AT YOUR OWN RISK. 

NOTE: Not all NIH links contain a link to the full study. But look in the upper right corner of the NIH page and you might see a link to an EPUB or PDF which should contain the full study.

Name: Cordyceps sinensis

Common names: Cordyceps , aweto , caterpillar fungus , Cs-4 , Dong Chong Xia Cao , keera jhar , keeda ghas , semitake , tochukaso , XinGanBao , yarshagumba , yartsa gunbu , yatsa gunbu , Zhiling.

Cordyceps sinensis is the fungus found in Tibet above the altitude of 3800m. It's also called "Yarsa gumba" and "Yarcha gumba". It's the one that takes over caterpillars, and fetches a VERY high price in Asian markets. Traditional folk medicine uses Cordyceps to treat 21 illnesses such as asthma, erectile dysfunction, cancer, TB, cough and cold, diabetes. It is said to give people increased health and vitality and energy by acting as an anti-inflammatory.

Cordyceps shows promise, but more studies need to be done. Cordyceps is currently harvested non-sustainably from the wild. I know of no commercial production of Cordyceps.

Medical Health Guide gives more details such as dosage (5-10g daily) and side effects (no major problems have been reported yet.)

NOTE: I try to get a free link to the full study. Failing that, I link to what I can. 

- Study on treatment vs pulmonary fibrosis
Accordingly, HSM reduces inflammatory cell accumulation in bronchoalveolar lavage fluid and proinflammatory cytokines levels in lung tissues.
Huang TT, Lai HC, Ko YF, Ojcius DM, Lan YW, Martel J, Young JD, Chong KY. Hirsutella sinensis mycelium attenuates bleomycin-induced pulmonary inflammation and fibrosis in vivo. Sci Rep. 2015 Oct 26; 5:15282. doi: 10.1038/srep15282. Link to NIH.

- As anti-inflammatory

Huang TT, Chong KY, Ojcius DM, Wu YH, Ko YF, Wu CY, Martel J, Lu CC, Lai HC, Young JD. Hirsutella sinensis mycelium suppresses interleukin-1β and interleukin-18 secretion by inhibiting both canonical and non-canonical inflammasomes. Sci Rep. 2013; 3:1374. doi: 10.1038/srep01374. Link to NIH.

- Info from Drugs.com.
  • 60+ studies on this page alone. See footnotes in the actual link.
  • Dosing supported by product quality data is unavailable, and many herbal supplements on the market contain varying undefined levels of this product. Cordyceps 3 to 6 g/day has been used in patients with chronic renal failure for periods ranging from days to years.
  • Possible reactions: Mild GI discomfort, including diarrhea, dry mouth, and nausea, has been reported.
  • Animal experiments suggest a protective role for cordyceps in radiation- and chemotherapy-induced injury, with increased survival times demonstrated in mice. 
  • A vasodilatory action has been reported in anesthetized dogs, and hypotensive (lowering blood pressure) and vaso-relaxant effects have been demonstrated in rats. 
  • Long-term, open-label clinical studies in cardiac failure have described cordyceps' effect in improving cardiac function, arrhythmias, and overall quality of life, but are yet to be substantiated by large, high-quality clinical trials.  
  • Clinical studies conducted in asthma, chronic obstructive pulmonary disease, and bronchitis have suggested efficacy for cordyceps.  
  • Action on steroidogenesis and testosterone have been shown.
  • One report of hypersensitivity with use of cordyceps exists. 4 Mild GI discomfort, including diarrhea, dry mouth, and nausea, has been reported in clinical studies.
  • Cordyceps is considered to be safe; an oral median lethal dose could not be defined. Doses in mice of 80 g/kg body weight did not cause death.
The studies from this link are reproduced here:

1. Sung GH, Hywel-Jones NL, Sung JM, Luangsa-Ard JJ, Shrestha B, Spatafora JW. Phylogenetic classification of Cordyceps and the clavicipitaceous fungi. Stud Mycol . 2007; 57:5-59.

2. Zhu JS, Halpern GM, Jones K. The scientific rediscovery of an ancient Chinese herbal medicine: Cordyceps sinensis : part I. J Altern Complement Med . 1998; 4(3):289-303. Link to online PDF.

3. Li SP, Yang FQ, Tsim KW. Quality control of Cordyceps sinensis , a valued traditional Chinese medicine. J Pharm Biomed Anal . 2006; 41(5):1571-1584. Link to online PDF.

4. Holliday JC, Cleaver MP. Medicinal value of the caterpillar fungi species of the genus Cordyceps (Fr.) Link (Ascomycetes). A review. Int J Med Mushr . 2008; 10(3):219-234. Abstract from Bioresearch Update. This page has a link to the full study as a PDF on Springer.

5. Zhu JS, Halpern GM, Jones K. The scientific rediscovery of a precious ancient Chinese herbal regimen: Cordyceps sinensis : part II. J Altern Complement Med . 1998; 4(4):429-457. Link to full study PDF on Gano-Therapy.

6. Huang LF, Liang YZ, Guo FQ, Zhou ZF, Cheng BM. Simultaneous separation and determination of active components in Cordyceps sinensis and Cordyceps militarris by LC/ESI-MS. J Pharm Biomed Anal . 2003; 33(5):1155-1162. Link to NIH abstract.

7. Paterson RR. Cordyceps: a traditional Chinese medicine and another fungal therapeutic biofactory? Phytochemistry . 2008; 69(7):1469-1495. Link to NIH abstract. Full study as PDF.

8. Ng TB, Wang HX. Pharmacological actions of Cordyceps, a prized folk medicine. J Pharm Pharmacol . 2005; 57(12):1509-1519. NIH abstract. Link to JPP, on right click "get pdf" for full study.

9. Wojcikowski K, Johnson DW, Gobé G. Medicinal herbal extracts—renal friend or foe? Part two: herbal extracts with potential renal benefits. Nephrology (Carlton) . 2004; 9(6):400-405. Full study on Wiley. On right side of webpage click "get pdf".

10. Ji DB, Ye J, Li CL, Wang YH, Zhao J, Cai SQ. Antiaging effect of Cordyceps sinensis extract. Phytother Res . 2009; 23(1):116-122. Full study on Wiley. On right side of webpage click "get pdf". Full study from ResearchGate.

11. Wang Y, Wang M, Ling Y, Fan W, Wang Y, Yin H. Structural determination and antioxidant activity of a polysaccharide from the fruiting bodies of cultured Cordyceps sinensis . Am J Chin Med . 2009; 37(5):977-989. Link to abstract on WorldScientific.

12. Won KJ, Lee SC, Lee CK, et al. Cordycepin attenuates neointimal formation by inhibiting reactive oxygen species-mediated responses in vascular smooth muscle cells in rats. J Pharmacol Sci. 2009; 109(3):403-412. Abstract from NIH.

13. Nishizawa K, Torii K, Kawasaki A, et al. Antidepressant-like effect of Cordyceps sinensis in the mouse tail suspension test. Biol Pharm Bull. 2007; 30(9):1758-1762. Full study PDF.

14. Rao YK, Fang SH, Tzeng YM. Evaluation of the anti-inflammatory and anti-proliferation tumoral cells activities of Antrodia camphorata , Cordyceps sinensis, and Cinnamomum osmophloeum bark extracts. J Ethnopharmacol. 2007; 114(1):78-85. Abstract from ScienceDirect. Link to NIH full study contains links to epub and PDF.

15. Zhang W, Li J, Qiu S, Chen J, Zheng Y. Effects of the exopolysaccharide fraction (EPSF) from a cultivated Cordyceps sinensis on immunocytes of H22 tumor bearing mice. Fitoterapia. 2008; 79(3):168-173. Full study at NIH.

16. Chen Y, Guo H, Du Z, Liu XZ, Che Y, Ye X. Ecology-based screen identifies new metabolites from a Cordyceps-colonizing fungus as cancer cell proliferation inhibitors and apoptosis inducers. Cell Prolif. 2009; 42(6):838-847.

17. Wu WC, Hsiao JR, Lian YY, Lin CY, Huang BM. The apoptotic effect of cordycepin on human OEC-M1 oral cancer cell line. Cancer Chemother Pharmacol. 2007; 60(1):103-111.

18. Lee SJ, Kim SK, Choi WS, Kim WJ, Moon SK. Cordycepin causes p21WAF1-mediated G2/M cell-cycle arrest by regulating c-Jun N-terminal kinase activation in human bladder cancer cells. Arch Biochem Biophys. 2009; 490(2):103-109.

19. Zhang G, Huang Y, Bian Y, Wong JH, Ng TB, Wang H. Hypoglycemic activity of the fungi Cordyceps militaris , Cordyceps sinensis , Tricholoma mongolicum , and Omphalia lapidescens in streptozotocin-induced diabetic rats. Appl Microbiol Biotechnol. 2006; 72(6):1152-1156. Link to NIH abstract.

20. Matsuda H, Akaki J, Nakamura S, et al. Apoptosis-inducing effects of sterols from the dried powder of cultured mycelium of Cordyceps sinensis . Chem Pharm Bull (Tokyo). 2009; 57(4):411-414.

21. Liu WC, Chuang WL, Tsai ML, Hong JH, McBride WH, Chiang CS. Cordyceps sinensis health supplement enhances recovery from taxol-induced leukopenia. Exp Biol Med (Maywood). 2008; 233(4):447-455. Link to abstract on Europepmc. For full article look for PDF link on right.

22. Liu WC, Wang SC, Tsai ML, et al. Protection against radiation-induced bone marrow and intestinal injuries by Cordyceps sinensis , a Chinese herbal medicine. Radiat Res. 2006; 166(6):900-907. Full study from BioOne.org.

23. Chiou WF, Chang PC, Chou CJ, Chen CF. Protein constituent contributes to the hypotensive and vasorelaxant activities of Cordyceps sinensis. Life Sci. 2000; 66(14):1369-1376.

24. Li HP, Hu Z, Yuan JL, et al. A novel extracellular protease with fibrinolytic activity from the culture supernatant of Cordyceps sinensis : purification and characterization. Phytother Res . 2007; 21(12):1234-1241.

25. Cho HJ, Cho JY, Rhee MH, Park HJ. Cordycepin (3'-deoxyadenosine) inhibits human platelet aggregation in a cyclic AMP- and cyclic GMP-dependent manner. Eur J Pharmacol . 2007; 558(1-3):43-51.

26. Koh JH, Kim JM, Chang UJ, Suh HJ. Hypocholesterolemic effect of hot-water extract from mycelia of Cordyceps sinensis . Biol Pharm Bull . 2003;26(1):84-87.

27. Lo HC, Hsu TH, Tu ST, Lin KC. Anti-hyperglycemic activity of natural and fermented Cordyceps sinensis in rats with diabetes induced by nicotinamide and streptozotocin. Am J Chin Med . 2006;34(5):819-832.

28. Lo HC, Tu ST, Lin KC, Lin SC. The anti-hyperglycemic activity of the fruiting body of Cordyceps in diabetic rats induced by nicotinamide and streptozotocin. Life Sci . 2004;74(23):2897-2908.

29. Zhang G, Huang Y, Bian Y, Wong JH, Ng TB, Wang H. Hypoglycemic activity of the fungi Cordyceps militaris , Cordyceps sinensis , Tricholoma mongolicum , and Omphalia lapidescens in streptozotocin-induced diabetic rats. Appl Microbiol Biotechnol . 2006;72(6):1152-1156.

30. Zhao CS, Yin WT, Wang JY, et al. CordyMax Cs-4 improves glucose metabolism and increases insulin sensitivity in normal rats. J Altern Complement Med . 2002;8(3):309-314.

31. Balon TW, Jasman AP, Zhu JS. A fermentation product of Cordyceps sinensis increases whole-body insulin sensitivity in rats. J Altern Complement Med . 2002;8(3):315-323.

32. Hockaday TD. Two herbal preparations, Cordyceps Cs4 and Cogent db: do they act on blood glucose, insulin sensitivity, and diabetes as “viscous dietary fibers?” J Altern Complement Med . 2002 ; 8(4):403-405.

33. Ko WS, Hsu SL, Chyau CC, Chen KC, Peng RY. Compound Cordyceps TCM-700C exhibits potent hepatoprotective capability in animal model. Fitoterapia . 2010; 81(1):1-7.

34. Li Y, Xue WJ, Tian PX, et al. Clinical application of Cordyceps sinensis on immunosuppressive therapy in renal transplantation. Transplant Proc . 2009; 41(5):1565-1569.

35. Liu YK, Shen W. Inhibitive effect of Cordyceps sinensis on experimental hepatic fibrosis and its possible mechanism. World J Gastroenterol . 2003;9(3):529-533.

36. Kuo CF, Chen CC, Lin CF, et al. Abrogation of streptococcal pyrogenic exotoxin B-mediated suppression of phagocytosis in U937 cells by Cordyceps sinensis mycelium via production of cytokines. Food Chem Toxicol . 2007;45(2):278-285.

37. Yoon TJ, Yu KW, Shin KS, Suh HJ. Innate immune stimulation of exo-polymers prepared from Cordyceps sinensi s by submerged culture. Appl Microbiol Biotechnol . 2008; 80(6):1087-1093.

38. Zhou X, Luo L, Dressel W, et al. Cordycepin is an immunoregulatory active ingredient of Cordyceps sinensis . Am J Chin Med . 2008; 36(5):967-980.

39. Jordan JL, Hirsch GM, Lee TD. C. sinensis ablates allograft vasculopathy when used as an adjuvant therapy with cyclosporin A. Transpl Immunol . 2008;19(3-4):159-166.

40. Cheung JK, Li J, Cheung AW, et al. Cordysinocan, a polysaccharide isolated from cultured Cordyceps, activates immune responses in cultured T-lymphocytes and macrophages: signaling cascade and induction of cytokines. J Ethnopharmacol . 2009;124(1):61-88.

41. Jordan JL, Sullivan AM, Lee TD. Immune activation by a sterile aqueous extract of Cordyceps sinensis : mechanism of action. Immunopharmacol Immunotoxicol . 2008;30(1):53-70.

42. Kuo MC, Chang CY, Cheng TL, Wu MJ. Immunomodulatory effect of exo-polysaccharides from submerged cultured Cordyceps sinensis: enhancement of cytokine synthesis, CD11b expression, and phagocytosis. Appl Microbiol Biotechnol . 2007;75(4):769-775.

43. Kuo YC, Tsai WJ, Wang JY, Chang SC, Lin CY, Shiao MS. Regulation of bronchoalveolar lavage fluids cell function by the immunomodulatory agents from Cordyceps sinensis . Life Sci . 2001:68(9):1067-1082.

44. Kim HG, Shrestha B, Lim SY, et al. Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-ΚB through Akt and p38 inhibition in RAW 264.7 macrophage cells. Eur J Pharmacol . 2006;545(2-3):192-199.

45. Wu Y, Sun H, Qin F, Pan Y, Sun C. Effect of various extracts and a polysaccharide from the edible mycelia of Cordyceps sinensis on cellular and humoral immune response against ovalbumin in mice. Phytother Res . 2006; 20(8):646-652.

46. Siu KM, Mak DH, Chiu PY, Poon MK, Du Y, Ko KM. Pharmacological basis of 'Yin-nourishing' and 'Yang-invigorating' actions of Cordyceps, a Chinese tonifying herb. Life Sci . 2004; 76(4):385-395.

47. Park DK, Choi WS, Park PJ, et al. Immunoglobulin and cytokine production from mesenteric lymph node lymphocytes is regulated by extracts of Cordyceps sinensis in C57Bl/6N mice. J Med Food. 2008; 11(4):784-788.

48. Leu SF, Chien CH, Tseng CY, Kuo YM, Huang BM. The in vivo effect of Cordyceps sinensis mycelium on plasma corticosterone level in male mouse. Biol Pharm Bull . 2005;28(9):1722-1725.

49. Kuo CF, Chen CC, Luo YH, et al. Cordyceps sinensis mycelium protects mice from group A streptococcal infection. J Med Microbiol . 2005;54(pt 8):795-802.

50. Chen JL, Chen YC, Yang SH, Ko YF, Chen SY. Immunological alterations in lupus-prone autoimmune (NZB/NZW) F1 mice by mycelia Chinese medicinal fungus Cordyceps sinensis -induced redistributions of peripheral mononuclear T lymphocytes. Clin Exp Med. 2009; 9(4):277-284.

51. Ka Wai Lee S, Kwok Wong C, Kai Kong S, Nam Leung K, Wai Kei Lam C. Immunomodulatory activities of HERBSnSENSES Cordyceps—in vitro and in vivo studies. Immunopharmacol Immunotoxicol. 2006; 28(2):341-360.

52. Herda TJ, Ryan ED, Stout JR, Cramer JT. Effects of a supplement designed to increase ATP levels on muscle strength, power output, and endurance. J Int Soc Sports Nutr . 2008;5:3.

53. Earnest CP, Morss GM, Wyatt F, et al. Effects of a commercial herbal-based formula on exercise performance in cyclists. Med Sci Sports Exerc . 2004;36(3):504-509.

54. Colson SN, Wyatt FB, Johnston DL, Autrey LD, FitzGerald YL, Earnest CP. Cordyceps sinensis - and Rhodiola rosea-based supplementation in male cyclists and its effect on muscle tissue oxygen saturation. J Strength Cond Res . 2005;19(2):358-363.

55. Parcell AC, Smith JM, Schulthies SS, Myrer JW, Fellingham G. Cordyceps Sinensis (CordyMax Cs-4) supplementation does not improve endurance exercise performance. Int J Sport Nutr Exerc Metab . 2004;14(2):236-242.

56. Shahed AR, Kim SI, Shoskes DA. Down-regulation of apoptotic and inflammatory genes by Cordyceps sinensis extract in rat kidney following ischemia/reperfusion. Transplant Proc . 2001;33(6):2986-2987.

57. Li CY, Chiang CS, Tsai ML, et al. Two-sided effect of Cordyceps sinensis on dendritic cells in different physiological stages. J Leukoc Biol . 2009;85(6):987-995.

58. Yue GG, Lau CB, Fung KP, Leung PC, Ko WH. Effects of Cordyceps sinensis , Cordyceps militaris and their isolated compounds on ion transport in Calu-3 human airway epithelial cells. J Ethnopharmacol . 2008;117(1):92-101.

59. Ji DB, Ye J, Li CL, Wang YH, Zhao J, Cai SQ. Antiaging effect of Cordyceps sinensis extract. Phytother Res . 2009;23(1):116-122.

60. Huang YL, Leu SF, Liu BC, Sheu CC, Huang BM. In vivo stimulatory effect of Cordyceps sinensis mycelium and its fractions on reproductive functions in male mouse. Life Sci . 2004;75(9):1051-1062.

61. Wong KL, So EC, Chen CC, Wu RS, Huang BM. Regulation of steroidogenesis by Cordyceps sinensis mycelium extracted fractions with (hCG) treatment in mouse Leydig cells. Arch Androl . 2007;53(2):75-77.

62. Hsu CC, Tsai SJ, Huang YL, Huang BM. Regulatory mechanism of Cordyceps sinensis mycelium on mouse Leydig cell steroidogenesis. FEBS Lett . 2003;543(1-3):140-143.

63. Hsu CC, Huang YL, Tsai SJ, Sheu CC, Huang BM. In vivo and in vitro stimulatory effects of Cordyceps sinensis on testosterone production in mouse Leydig cells. Life Sci . 2003; 73(16):2127-2136.

64. Mizuha Y, Yamamoto H, Sato T, et al. Water extract of Cordyceps sinensis (WECS) inhibits the RANKL-induced osteoclast differentiation. Biofactors . 2007; 30(2):105-116.

65. Vogel JH, Bolling SF, Costello RB, et al. Integrating complementary medicine into cardiovascular medicine. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents (Writing Committee to Develop an Expert Consensus Document on Complementary and Integrative Medicine). J Am Coll Cardiol . 2005;46(1):184-221.

66. Wong EL, Sung RY, Leung TF, et al. Randomized, double-blind, placebo-controlled trial of herbal therapy for children with asthma. J Altern Complement Med . 2009;15(10):1091-1097.



- This page on Examine.com rates each study with a grade. 
The studies are also grouped by effect that was studied.
Really good page! If you go into each section by by effect, the link to the full study is there.

- University of Michigan page on Cordyceps.

- Zhang HW, Lin ZX, Tung YS, Kwan TH, Mok CK, Leung C, Chan LS. Cordyceps sinensis (a traditional Chinese medicine) for treating chronic kidney disease. Cochrane Database of Systematic Reviews 2014, Issue 12. Art. No.: CD008353. DOI: 10.1002/14651858.CD008353.pub2.  Abstract and full study from Wiley.




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