J Nutr Health.  2019 Jun;52(3):258-267. 10.4163/jnh.2019.52.3.258.

Effects of Cordyceps militaris supplementation on the immune response and upper respiratory infection in healthy adults: a randomized, double-blind, placebo-controlled study

• Jung SJ
• Hwang JH
• Oh MR
• Chae SW

• KMID: 2450423
• DOI: http://doi.org/10.4163/jnh.2019.52.3.258

Abstract

PURPOSE
Upper respiratory tract infections are major causes of the common cold throughout the world. Cordyceps militaris (C. militaris) is a well-known functional food for its anti-fatigue and immunomodulating activities. On the other hand, there are no reports on the protective effect against upper respiratory tract infections (URI). This study was a 12 week randomized, double-blind, and placebo-controlled trial in healthy volunteers.
METHODS
A total of 100 subjects 20 ~ 70 years of age with a history of at least two colds in the year were enrolled in the study. The participants were required to record any adverse events and rate any cold-related incidents in a diary during the investigation period. The efficacy end point was the symptoms and incidence of URI, and changes in cytokines, IgA and natural killer (NK) cell activity.
RESULTS
The Cordyceps militaris group over 12 weeks showed no significant impact on the incidence and symptomatology of URI compared to the placebo group. On the other hand, the experimental group showed significantly higher NK cell activity (p = 0.047) and IgA level (p = 0.035) compared to the placebo group. The NK-cell activity and IgA level were increased significantly by Cordyceps militaris over 12 weeks.
CONCLUSION
The results suggest the possible beneficial immunomodulating effects, but the protective effects on URI could not be demonstrated under these conditions. Additional research will be needed to determine the efficacy and mechanisms of Cordyceps militaris function.

Keyword

Cordyceps militaris; immune; upper respiratory tract infection; NK-cell; IgA

MeSH Terms

Adult*
Common Cold
Cordyceps*
Cytokines
Functional Food
Hand
Healthy Volunteers
Humans
Immunoglobulin A
Incidence
Killer Cells, Natural
Respiratory Tract Infections
Cytokines
Immunoglobulin A

Figure

• 

  Fig. 1 CONSORT diagram showing the study flow

Reference

1. Heikkinen T, Järvinen A. The common cold. Lancet. 2003; 361(9351):51–59.

2. Fendrick AM, Monto AS, Nightengale B, Sarnes M. The economic burden of non-influenza-related viral respiratory tract infection in the United States. Arch Intern Med. 2003; 163(4):487–494.

3. Eccles R. Understanding the symptoms of the common cold and influenza. Lancet Infect Dis. 2005; 5(11):718–725.

4. Johnston S, Holgate S. Epidemiology of viral respiratory tract infections. In : Myint S, Taylor-Robinson D, editors. Viral and Other Infections of the Human Respiratory Tract. London: Chapman & Hall;1996. p. 1–38.

5. National Health Insurance Service (KR). Classifieds disease compensation and health care costs [Internet]. Wonju: National Health Insurance Service;2014. cited 2018 August 20. Available from: http://kosis.kr/statHtml/statHtml.do?orgId=350&tblId=DT_35001_A071111.

6. Kim JA, Park JH, Kim BY, Kim DS. The trend of acute respiratory tract infections and antibiotic prescription rates in outpatient settings using health insurance data. Korean. Korean J Clin Pharm. 2017; 27(3):186–194.

7. Hung YF, Thomason MJ, Rhys-williams W, Lloyd AW, Hanlon GW. Chiral inversion of 2-phenylpropionic acid by cordyceps militaris. J Appl Bacteriol. 1996; 81(3):242–250.

8. Iwashima A, Kawasaki Y, Nosaka K, Nishimura H. Effect of thiamin on cordycepin sensitivity in Saccharomyces cerevisiae. FEBS Lett. 1992; 311(1):60–62.

9. Lee H, Yang M, Park T. Inhibitory effect of Cordyceps Militaris water extracts on sarcoma-180 cell-induced ascities tumor in ICR mice. Korean J Nutr. 2003; 36(10):1022–1029.

10. Shin S, Moon S, Park Y, Kwon J, Lee S, Lee CK, et al. Role of cordycepin and adenosine on the phenotypic switch of macrophages via induced anti-inflammatory cytokines. Immune Netw. 2009; 9(6):255–264.

11. Yue K, Ye M, Lin X, Zhou Z. The artificial cultivation of medicinal Caterpillar fungus, Ophiocordyceps sinensis (ascomycetes): a review. Int J Med Mushrooms. 2013; 15(5):425–434.

12. Guan YJ, Hu Z, Hou M. Effect of Cordyceps sinensis on T-lymphocyte subsets in chronic renal failure. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1992; 12(6):338–339. 323

13. Bao ZD, Wu ZG, Zheng F. Amelioration of aminoglycoside nephrotoxicity by Cordyceps sinensis in old patients. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1994; 14(5):271–273. 259

14. Kuo YC, Tsai WJ, Shiao MS, Chen CF, Lin CY. Cordyceps sinensis as an immunomodulatory agent. Am J Chin Med. 1996; 24(2):111–125.

15. Kim GY, Ko WS, Lee JY, Lee JO, Ryu CH, Choi BT, et al. Water extract of Cordyceps militaris enhances maturation of murine bone marrow-derived dendritic cells in vitro. Biol Pharm Bull. 2006; 29(2):354–360.

16. Lee HH, Park H, Sung GH, Lee K, Lee T, Lee I, et al. Anti-influenza effect of Cordyceps militaris through immunomodulation in a DBA/2 mouse model. J Microbiol. 2014; 52(8):696–701.

17. Kang IS, Kim HJ, Lee TH, Kwon YS, Son MW, Kim CK. Effects of Cordyceps militaris on immune activity. Yakhak Hoeji. 2014; 58(2):81–90.

18. Kang HJ, Baik HW, Kim SJ, Lee SG, Ahn HY, Park JS, et al. Cordyceps militaris enhances cell-Mediated immunity in healthy Korean men. J Med Food. 2015; 18(10):1164–1172.

19. Nan JX, Park EJ, Yang BK, Song CH, Ko G, Sohn DH. E\Antifibrotic effect of extracellular biopolymer from submerged mycelial cultures of Cordyceps militaris on liver fibrosis induced by bile duct ligation and scission in rats. Arch Pharm Res. 2001; 24(4):327–332.

20. Stone EA, Quartermain D. Greater behavioral effects of stress in immature as compared to mature male mice. Physiol Behav. 1997; 63(1):143–145.

21. Won SY, Park EH. Anti-inflammatory and related pharmacological activities of cultured mycelia and fruiting bodies of Cordyceps militaris. J Ethnopharmacol. 2005; 96(3):555–561.

22. Kiho T, Hui J, Yamane A, Ukai S. Polysaccharides in fungi. XXXII. Hypoglycemic activity and chemical properties of a polysaccharide from the cultural mycelium of Cordyceps sinensis. Biol Pharm Bull. 1993; 16(12):1291–1293.

23. Kiho T, Yamane A, Hui J, Usui S, Ukai S. Polysaccharides in fungi. XXXVI. Hypoglycemic activity of a polysaccharide (CS-F30) from the cultural mycelium of Cordyceps sinensis and its effect on glucose metabolism in mouse liver. Biol Pharm Bull. 1996; 19(2):294–296.

24. de Vrese M, Winkler P, Rautenberg P, Harder T, Noah C, Laue C, et al. Probiotic bacteria reduced duration and severity but not the incidence of common cold episodes in a double blind, randomized, controlled trial. Vaccine. 2006; 24(44-46):6670–6674.

25. Kurugöl Z, Akilli M, Bayram N, Koturoglu G. The prophylactic and therapeutic effectiveness of zinc sulphate on common cold in children. Acta Paediatr. 2006; 95(10):1175–1181.

26. Roll S, Nocon M, Willich SN. Attenuation of common cold symptoms by encapsulated juice powder concentrate. Eur J Integr Med. 2010; 2(4):213.

27. Jawad M, Schoop R, Suter A, Klein P, Eccles R. Safety and efficacy profile of Echinacea purpurea to prevent common cold episodes: a randomized, double-blind, placebo-controlled trial. Evid Based Complement Alternat Med. 2012; 2012:841315.

28. Vitetta L, Coulson S, Beck SL, Gramotnev H, Du S, Lewis S. The clinical efficacy of a bovine lactoferrin/whey protein Ig-rich fraction (Lf/IgF) for the common cold: a double blind randomized study. Complement Ther Med. 2013; 21(3):164–171.

29. Predy GN, Goel V, Lovlin R, Donner A, Stitt L, Basu TK. Efficacy of an extract of North American ginseng containing poly-furanosyl-pyranosyl-saccharides for preventing upper respiratory tract infections: a randomized controlled trial. CMAJ. 2005; 173(9):1043–1048.

30. Barrett B, Locken K, Maberry R, Schwamman J, Brown R, Bobula J, et al. The Wisconsin Upper Respiratory Symptom Survey (WURSS): a new research instrument for assessing the common cold. J Fam Pract. 2002; 51(3):265.

31. Orange JS, Ballas ZK. Natural killer cells in human health and disease. Clin Immunol. 2006; 118(1):1–10.

32. Watters RJ, Liu X, Loughran TP Jr. T-cell and natural killer-cell large granular lymphocyte leukemia neoplasias. Leuk Lymphoma. 2011; 52(12):2217–2225.

33. Bar-On Y, Seidel E, Tsukerman P, Mandelboim M, Mandelboim O. Influenza virus uses its neuraminidase protein to evade the recognition of two activating NK cell receptors. J Infect Dis. 2014; 210(3):410–418.

34. Sato N, Kikuchi S, Sato K. Quantifying the stress induced by distress in patients with lumbar disc herniation in terms of natural killer cell activity measurements: chromium release assay versus multiparameter flow cytometric assay. Spine. 2002; 27(19):2095–2100.

35. Culley FJ. Natural killer cells in infection and inflammation of the lung. Immunology. 2009; 128(2):151–163.

36. Macpherson AJ, McCoy KD, Johansen FE, Brandtzaeg P. The immune geography of IgA induction and function. Mucosal Immunol. 2008; 1(1):11–22.

37. Rai A, Nast C, Adler S. Henoch-Schönlein purpura nephritis. J Am Soc Nephrol. 1999; 10(12):2637–2644.

38. Müller WE, Weiler BE, Charubala R, Pfleiderer W, Leserman L, Sobol RW, et al. Cordycepin analogues of 2′,5′-oligoadenylate inhibit human immunodeficiency virus infection via inhibition of reverse transcriptase. Biochemistry. 1991; 30(8):2027–2033.

39. Delacroix DL, Dive C, Rambaud JC, Vaerman JP. IgA subclasses in various secretions and in serum. Immunology. 1982; 47(2):383–385.