Concluding Remarks

G. lucidum is a well-regarded Asian herbal remedy with a long and impressive range of applications. Global consumption of G. lucidum is high, and an increasingly large series of patented and commercially available products that incorporate G. lucidum as an active ingredient are available as food supplements. These include extracts and isolated constituents in various formulations and these are marketed worldwide in the form of capsules, creams, hair tonics, and syrups (6,182). The various postulated health benefits of G. lucidum are outlined in Figure 5, and a summary of the experimental studies described in this chapter, with our comments, on the putative therapeutic effects of G. lucidum is presented in Table 2.

In conclusion, studies on G. lucidum composition, cultivation, and reputed effects are still being carried out, and several new studies have been published since this paper was drafted. However, convincing evidence of direct effects of G. lucidum on human health is lacking to date, even though the mushroom is widely promoted and consumed. Observational and anecdotal reports of benefits have not as yet been substantiated by well-controlled clinical trials or reliable scientific data. The G. lucidum preparations used have

Figure 5 Postulated, but as yet unvalidated, health benefits of Lingzhi (G. lucidum).

TABLE 2 Summary of Experimental Studies3 on the Putative Therapeutic Effects of the Lingzhi Mushroom [Ganoderma lucidum)

Effect tested

Type of study

Reported effect

Comment

Ref.

Viral infection

Viral proliferation

Viral infection

Recovery from or progression of viral infection

Bacterial infection

Bacterial proliferation

Cell culture and in vitro

Human intervention trials

In vitro and animal studies

Inhibitory effect against some viruses, particularly herpes simplex; synergistic or additive effects with antiviral drugs reported.

Some isolated triterpenes inhibited (HIV)-I reverse transcriptase and protease.

Promoted recovery from postherpetic neuralgia (n = 4) and reportedly also aided recovery in a small (n = 4) trial on hepatitis B patients. No improvement in quality of life or immune status was seen in HIV patients (n = 68) given a mix of Chinese herbs together with lingzhi.

In vitro inhibitory effect reported against some bacteria; additive or

G. lucidum may have an inhibitory effect on viral proliferation, and the possible synergistic effect with established antiviral drugs is interesting; further in vitro studies are needed.

Only 3 trials published to date; these were small, poorly designed, and uncontrolled studies and do not provide convincing scientific evidence for G. lucidum in promoting recovery from viral infection; well-planned, controlled clinical trials are needed.

No human trials to date; experimental evidence of possible interaction

60,84,86, 112-115

1 19,121

Cancer Tumor growth Animal studies and human clinical trials synergistic effect reported with antibiotic drugs, but indication of some antagonistic effect also seen.

Administration of G. lucidum to animals (i.p or o.p) inhibited growth of implanted/induced tumors (see Table 1). Human studies of acute myeloblasts leukemia and advanced nasopharyngeal carcinoma reported improvement in patients treated with high-dose G. lucidum extract in combination with conventional therapy.

with antibiotics is interesting, as G. lucidum may help lower MIC values of potentially cytotoxic drugs. However, antagonistic effects must be clarified, and testing for possible antibacterial effect against antibiotic resistant strains would be useful.

Antitumor activity appears related to polysaccharide content of mushroom. Only two human trials reported to date; there were small (n = 4 and n = 5) and uncontrolled, involved advanced illness, and G. lucidum was given in conjunction with standard therapy; contribution of G. lucidum to reported improvement in patients is not clear.

46,51-53,70, 121,126-128

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Table 2 Continued

Effect tested

Type of study

Cancer

Growth and activation of cancer and immune cells

Cell culture and cells ex vivo and in vitro

Immune status Immunomodulation Animal studies and cells ex vivo ro ro

Reported effect

Comment

Ref.

Incubation with G. lucidum caused activation of cultured macrophages and T lymphocytes; increase in cytokine production; activated macrophages inhibited growth of cultured cancer cells, promoted apoptosis and differentiation; effects on cancer cells not seen with untreated macrophages or with G. lucidum alone; G. lucidum induced phase II enzymes in cultured cells; terpenes from G. lucidum reported to inhibit DNA polymerase in vitro.

Enhanced lymphocyte proliferation, antibody production, and recovery of the immune system in irradiated

Direct effects on cancer cells may be due to triterpene-mediated inhibition of cell division and inhibition of DNA polymerase. Indirect effects appear to be more pronounced and mediated by polysaccharide-induced effects on immune cells.

Opposing effects-activation and suppression—seen with different constituents. Studies often poorly

CVD Blood pressure and In vitro and cholesterol animal synthesis studies;

human intervention trial mice reported. An isolated protein (LZ-8) and methanolic extracts of G. lucidum showed immunosuppressive effects, such as delaying rejection time of allografts in mice.

Inhibition of cholesterol synthesis and ACE demonstrated in vitro; hypotensive effect seen in some animal studies; hypotensive and small cholesterol-lowering effect reported in human intervention trial of 40 hypertensive subjects treated with G. lucidum for 6 months.

described and appear uncontrolled. Further study is needed.

Some evidence that G. lucidum has potential as a hypotensive and hypocholesterolemic agent; effects on blood pressure may be due to ACE inhibition; effects on cholesterol may be mediated by a combination of inhibition of cholesterol synthesis and blocking of sterol receptors in Gl tract owing to structural similarity between lanosterol-derived terpenes and cholesterol. Further study needed, as only one human trial published to date.

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Table 2 Continued

Effect tested Type of study

CVD Platelet aggregation In vitro and and blood animal clotting studies

CVD Glycemic control Animal studies and human intervention trial

Inflammation Inflammatory In vitro and response animal studies ro

Reported effect

Comment

Ref.

Adenosine, adenosine derivative, and ganodermic acid S isolated from G. lucidum inhibited platelet aggregation; metalloprotease isolated from G. lucidum increased clotting time.

Polysaccharides isolated from G. lucidum shown to have hypoglycemic effect in mice. In a small, poorly controlled clinical trial, G. lucidum supplementation was reported to improve glycemic control in type I (n = 2) and type II (n = 2) diabetes mellitus patients, compared to 4 untreated control diabetic subjects.

Anti-inflammatory properties were shown in induced irritation

No in vivo studies published to date.

110,147-152

Positive hypoglycemic results in animal studies; however, there is a lack of data from well-designed human trials to support this claim.

46,57,61,154

Interesting results; however, no human trials published to date,

32,156,158

Inflammation PLA2 activity In vitro

Allergy Allergic response In vitro and human trials

(edema) in mice after oral and topical application of organic (terpenes-containing) extracts.

Some isolated triterpenes showed inhibitory effects against the enzyme PLA2 isolated from bee venom, hog pancreas, and snake venom. One triterpene (ganoderic acid T) reported to inhibit human recombinant PLA2.

Triterpenes from G. lucidum reported to have inhibited histamine release in vitro. No reports of allergic response to ingestion of G. lucidum, but three reports of aerosensitization in atopic subjects.

and no data on mechanism of antiinflammatory effect of triterpenes presented.

Results indicate that different triterpenes may be active only against certain types of PLA2. Specific triterpenes should be further studied in specific models of PLA2 inhibition and the downstream antiinflammatory effects of this.

No strong evidence of antiallergenic properties; further study needed. However, possible allergic reaction to G. lucidum should be considered, especially in patients with respiratory or allergic disorders or in association with topical application.

158-162

12,77,157, 163-165

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Table 2 Continued

Effect tested

Type of study

Reported effect

Comment

Ref.

Antioxidant

ROS scavenging and antioxidant bioavailability

In vitro and human intervention trial

Liver injury

Induced liver injury Animal studies

G. lucidum found to possess antioxidant properties in in vitro models; reported to scavenge superoxide and hydroxyl radical, to protect DNA from ROS and decrease lipid peroxidation. In a human bioavailability study (n = 10), plasma antioxidant power increased after G. lucidum intake.

G. lucidum reported to show antifibrotic and hepatoprotective effects after CCI4 or ethanol in animal models induced liver injury.

Not yet known which antioxidants from G. lucidum are absorbed or if the absorbed antioxidants have any in vivo protective effect. Further study needed.

169-175

No histological data presented; whether the effect of G lucidum is truly protective, indicates faster recovery from damage, or improved clearing of plasma biomarkers of liver injury should be further investigated.

142,176-180

a The studies summarized in this table are those published in English in at least abstract form.

often not been well defined in terms of the source, growing conditions, means of identification of the mushroom as G. lucidum, contamination, heavy metal content, batch-to-batch variation, method of extraction/preparation, or dosage. Most studies have been performed on animals or in cell culture models, and experimental studies have often been small, poorly designed, and inadequately controlled. The great wealth of chemical data and anecdotal evidence on effects of G. lucidum needs now to be complemented by reliable experimental and clinical data from human trials to clearly establish whether the reported health-related effects are valid and significant. Quality control procedures to define and standardize G. lucidum preparations, in addition to well-designed animal and cell culture studies, are needed to determine mechanisms of action and to help characterize the active component(s) of this putative medicinal mushroom.

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