Reishi

Reishi (Ganoderma lucidum) is a fungus from the family of Ganodermataceae. In nature, the medicinal mushroom mainly colonizes living and dead deciduous woods. As a wood-dwelling Saprobiont or rot inhabitant, it is to be found in particular in moist dark forests of the subtropical and temperate climate zones of Asia, Europe as well as North and South America (1). In Japan „Rei Shi“, in China „Ling Zhi“ and in Korea „Youngzhi“ called, Ganoderma lucidum, with a history of more than 4000 years, counts to one of the longest used medicinal mushrooms of the East Asian region (2). Once reserved for only a few people, it was successfully cultivated more than 30 years ago. By its cultivation and the effects verified in studies Reishi gains as Mykotherapeutikum also beyond the asiatic area ever more popularity. On the meta-database of biomedical articles PubMed alone, 1036 hits on the topic “Reishi“ can be found as of 24.09.2019. The current research focus is on the oncological, cardiological and immunological fields as well as its application as a natural tonic (1).
 

Reishi provides a broad spectrum of substances. Currently more than 400 bioactive compounds have been described by analyses – including triterpenes, polysaccharides, nucleotides, enzymes, sterols, proteins, fatty acids, vitamins and minerals (3). The most important pharmacologically active compounds are triterpenes and polysaccharides, but the fungus should not be reduced to individual active substances. It is the interaction of its components that makes it such a valuable medicinal mushroom. In addition to the immunomodulating effect of Reishi, studies have also described anti-inflammatory, antiatherosclerotic, antioxidant, antidiabetic, antiviral (v. a. antiherpale), antimicrobial and tumor-inhibiting effects (1) (3).  
 

Ethnomedically, Reishi has been used as an anti-aging agent and tonic for thousands of years. Modern studies have confirmed that Reishi does not bear its names “mushroom of immortality“ or “mushroom of long life“ for nothing (2). Aging is a progressive physiological process that gradually leads to the loss of normal organ functions. A number of highly complex mechanisms are responsible for the aging process, many of which are still unexplained, but in which the involvement of oxidative stress is relatively certain (2)(8). In addition to oxidative damage and a decline in cognitive performance, ageing is also closely associated with the development of structural and functional immunodeficiencies. These immunological dysfunctions make older people more susceptible to bacterial and viral infections (2) (9). The bioactive components in Ganoderma lucidum, which mediate the anti-aging effect, are mainly polysaccharides, triterpenes, peptides and polysaccharide peptides, whereby the polysaccharides with their antioxidative and immunomodulatory effects are probably the main actors (2). Studies have shown that Reishi also has neuroprotective effects that are beneficial for cognitive aging (10).  
 

Almost every older man is affected to varying degrees by obstructive micturition symptoms caused by a benign enlarged prostate. The exact etiology of benign prostatic syndrome is still unclear but an interplay of several factors of a hormonal nature hypothesised. In clinical therapy, 5α reductase inhibitors are used for the pharmaceutical treatment of benign prostatic hyperplasia. This enzyme is necessary to convert testosterone in prostate cells into dihydrotestosterone (DHT). DHT is a more potent form of testosterone and is considered a probable factor for the genesis of benign prostate hyperplasia. Reishi (Ganoderma lucidum) is a natural 5α reductase inhibitor, which showed the highest activity in an analytical study of 19 medicinal mushroom extracts (11). Its theoretical effect on the prostate was also confirmed in human studies. In men over 50 years of age affected by benign prostate hyperplasia, treatment over  4-weeks or 8-weeks with Reishi (0.6 mg, 6 mg, 60 mg daily doses) significantly improved IPSS (International Prostate Symptom Score) symptoms compared to placebo, with an optimal dose established as 6 mg/day of  Reishi (12). The soothing effect of Reishi on benign prostate hyperplasia was confirmed in another double-blind, placebo-controlled study with 88 men over 49 years of age. The men took 6 mg Reishi extract or placebo daily for 12 weeks. Again, IPSS improved more than placebo (11). Side effects did not occur in either study (11) (12).
 

Atherosclerosis is a degenerative disease of the arterial vascular walls that leads to a variety of cardiovascular diseases. Atherosclerosis is caused by damage or dysfunction of the endothelium, which results in LDL molecules entering the  subendothelial layers. Oxidative stress and hypercholesterolemia are associated with an increased risk of cardiovascular disease (13). Previous studies have indicated that Reishi has beneficial effects on biomarkers of cardiovascular risk, DNA damage and inflammatory processes (14). In a randomized, double-blind crossover study, Chu et al. investigated the therapeutic effect of Reishi on borderline blood pressure and/or cholesterol elevation in 26 patients. Reishi intake improved insulin resistance, lowered triglyceride levels and increased HDL cholesterol levels compared to placebo. The results suggest that Reishi has a mild antidiabetic effect and improves dyslipidemia (15). The regulating effect of Reishi on lipid levels was also confirmed in an animal study from 2018. An aqueous Reishi extract (200 mg/kg body weight) lowered total cholesterol, triglyceride levels and LDL cholesterol in the animals (13). A study of isolated and perfused rat heart also demonstrated the cardioprotective effect of Reishi after global ischemia (45 minutes) and reperfusion (30 minutes).The administration of 400 mg Reishi extract/kg body weight over 15 days reduced the necrotic death of cardiomyocytes and reduced reperfusion contracture. The authors believe that the cardioprotective properties of Ganoderma-lucidum extract are largely due to its antioxidant properties (16).
 

Research results of recent years have increasingly highlighted Reishi as a protective and anticarcinogenic substance. In an animal model from 2017, rats fed high-fat foods received an aqueous or enzymatically prepared Reishi extract. Both extracts had a beneficial effect on intestinal health and the microbiome by decimating certain types of clostridia and reducing the secondary bile acids in the stool (e.g. intestinal carcinogenic deoxycholic acid and lithocholic acid). At the same time, the fecal mucin and the propionate, which is native to the appendix, increased, as did the fecal IgA in aqueous extracts (17). In the same year, an in vitro study showed that Reishi inhibits the yeast Candida  (18). Another animal model confirmed that Reishi regulates a disturbed intestinal flora and a derailed metabolism: in mice fed a high-fat diet and an aqueous extract of Reishi mycelium, int the intestinal flora the ratio of Firmicutes to Bacteroidetes – two bacterial strains that can influence body weight-improved. At the same time, body weight, inflammatory values, metabolic endotoxemia and insulin resistance decreased. This effect was reproducible by stool transmission to untreated mice fed a high-fat diet. According to the researchers, Reishi has prebiotic effects and can be used to restore a healthy intestinal environment. It is also a mycotherapeutic agent for obese people affected by obesity-related metabolic disorders (19).
 

In traditional Chinese medicine (TCM) Reishi is also used in cancer patients. It is usually recommended as an adjuvant treatment to oncological therapy for support of the immune system. Recent laboratory research and animal studies show promising results (20): Reishi shows both antiproliferative and cytotoxic effects on tumor cells – the latter by inhibiting the tumor cell cycle. Reishi also initiates cancer cell apoptosis and induces the cytotoxic activity of NK cells against different cancer cell lines. Two animal studies also suggest a possible anti-angiogenic effect of Reishi. In an in vitro study, Reishi was also successfully used in prostate cancer cell lines to block VEGF and TGF-β1, which are angiogenic factors. Reishi also achieved similar results in lung cancer cell lines in vitro (21). In 2016, a review examined five relevant randomized controlled human studies with a total of 373 patients. It was found that patients who took Reishi as part of their anti-cancer diet were 1.27 times more likely than patients who did not use the extract to respond to chemotherapy or radiotherapy. Reishi supplementation also significantly increased the host's immune response (CD3, CD4, CD8 lymphocytes). The activity of the natural killer cells, an indicator of the body's own tumor cell defence, was slightly increased. Patients in the Reishi group also showed a slightly better quality of life after mycotherapy than patients in the control group. According to the authors, however, the results of the review are to be regarded with limitations: the quality of the reviewed studies was poor and the study sample originated only from East Asia. According to researchers, the use of Reishi during therapy is inexpensive. In order to be able to make definitive statements, however, further high-quality and worldwide human studies must be awaited (20)(22)(23).

1) Cör, D. et al. 2018. Antitumour, Antimicrobial, Antioxidant and Antiacetylcholinesterase Effect of Ganoderma Lucidum Terpenoids and Polysaccharides: A Review. Molecules. 23(3). pii: E649. 
2) Wang, J. et al. 2017. Emerging Roles of Ganoderma Lucidum in Anti-Aging.Aging Dis. 8(6):691–707.
3) Ahmad, M. F. 2018. Ganoderma lucidum: Persuasive biologically active constituents and their health endorsement. Biomed Pharmacother. 107:507–19.
4) Wachtel-Galor, S. et al. 2011. Ganoderma lucidum (Lingzhi or Reishi): A Medicinal Mushroom. In: Benzie, I. F. F. et al. (Hrgs.). Herbal Medicine: Biomolecular and Clinical Aspects. CRC Press/Taylor & Francis, Boca Raton (FL). 2. Auflage.
5) Ma, C. et al. 2008. Differential protein expression in mouse splenic mononuclear cells treated with polysaccharides from spores of Ganoderma lucidum. Phytomedicine. 15(4):268–76.
6) Chen, S. D. et al. 2008. Effects of fermentation products of Ganoderma lucidum on growth performance and immunocompetence in weanling pigs. Arch Anim Nutr. 62(1):22–32.
7) Zhang, Y. et al. 2008. Effect of Ganoderma lucidum capsules on T lymphocyte subsets in football players on "living high-training low". Br J Sports Med. 42(10):819–22.
8) Zeyfang, A. et al. 2017. Basiswissen Medizin des Alterns und des alten Menschen. Springer Verlag, Berlin, Heidelberg. 3. Auflage.
9) Fuentes, E. et al. 2017 Immune System Dysfunction in the Elderly. An Acad Bras Cienc. 89(1):285–99.
10) Matsuzaki, H. et al. 2013. Antidepressant-like effects of a water-soluble extract from the culture medium of Ganoderma lucidum mycelia in rats. BMC Complement Altern Med. 13:370. doi: 10.1186/1472-6882-13-370.
11) Noguchi, M. et al. 2008. Randomized clinical trial of an ethanol extract of Ganoderma lucidum in men with lower urinary tract symptoms. Asian J Androl. 10(5):777–85.
12) Noguchi, M. et al. 2008. Effect of an extract of Ganoderma lucidum in men with lower urinary tract symptoms: a double-blind, placebo-controlled randomized and dose-ranging study. Asian J Androl. 10(4):651–8.
13) Rahman, M. A. et al. 2018. Evaluation of the Antioxidative and Hypo-cholesterolemic Effects of Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), in Ameliorating Cardiovascular Disease. Int J Med Mushrooms. 20(10):961–9.
14) Wachtel-Galor, S. et al. 2004. Ganoderma lucidum („Lingzhi“), a Chinese medicinal mushroom: biomarker responses in a controlled human supplementation study. Br J Nutr. 91(2):263–9.
15) Chu, T. T. et al. 2012. Study of potential cardioprotective effects of Ganoderma lucidum (Lingzhi): results of a controlled human intervention on trial. Br J Nutr. 107(7):1017–27.
16) Lasukova, T. V. et al. 2015. Cardioprotective Activity of Ganoderma lucidum Extract during Total Ischemia and Reperfusion of Isolated Heart. Bull Exp Biol Med. 158(6):739–41.
17) Yang, Y. et al. 2017. Feeding of the water extract from Ganoderma lingzhi to rats modulates secondary bile acids, intestinal microflora, mucins, and propionate important to colon cancer. Biosci Biotechnol Biochem. 81(9):1796–804.
18) Bhardwaj, A. et al. 2017. Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), Inhibits Candida Biofilms: A Metabolomic Approach. Int J Med Mushrooms. 19(8):685–96.
19) Chang, C. J. et al. 2015. Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nat Commun. 6:7489.
20) Santesso, N., Wieland, L. S. 2016. A Summary of a Cochrane Review: Ganoderma lucidum (Reishi mushroom) for the treatment of cancer. Eur J Integr Med. 8(5):619–20.
21) Unlu, A. et al. 2016. Ganoderma Lucidum (Reishi Mushroom) and cancer. J BUON. 21(4):792–8.
22): https://www.cochrane.org/de/CD007731/g-lucidum-reishi-pilz-glanzender-lackporling-zur-krebsbehandlung, aufgerufen am 04.06.2019.
23) Cheng, S., Silva, D. 2015. Ganoderma lucidum for cancer treatment: we are close but still not there. Integ Cancer Ther. 14(3):249–57.
24) Oka, S. et al. 2010. A water-soluble extract from culture medium of Ganoderma lucidum mycelia suppresses the development of colorectal adenomas. Hiroshima J Med Sci. 59(1):1–6.

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