Abstract
Background:
Ganoderma lucidum (G. lucidum) is one of the most popular edible mushrooms in the world which has various pharmacological components. Recently, some animal studies have investigated the lipid-lowering effects of G. lucidum and have shown contradictory results. This study aims to systematically review the effects of G. lucidum on lipid parameters in animal studies.
Materials and Methods:
A systematic search was conducted in the Medline database (PubMed), Scopus, Web of Science, Cochrane Library, and Google Scholar up to the end of January 2022. Only animal studies and all eligible randomized controlled trials (RCTs), including cluster RCTs and randomized crossover trials were included. The English language studies that assessed the effects of G. lucidum on lipid profiles including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and very low-density lipoproteins (VLDL) were selected.
Results:
Among 358 studies, 49 articles were included in the systematic review and meta-analysis. G. lucidum consumption was associated with decreased levels of TG (standardized mean difference [SMD] = −1.52, 95% CI: −1.79, −1.24), TC (SMD = −1.51, 95% CI: −1.75, −1.27), LDL-C (SMD = −2.03, 95% CI: −2.37, −1.69) and VLDL (SMD =-1.06, 95% CI: −1.638, −0.482). Furthermore, G. lucidum consumption was associated with increased levels of HDL-C (SMD = 1.03, 95% CI: 0.73, 1.33).
Conclusion:
G. lucidum has favorable effects on TG, TC, LDL-C, HDL-C, and VLDL. Different doses of G. lucidum have various degrees of effectiveness on lipid profiles.
Keywords: Agaricales, dyslipidemias, reishi
INTRODUCTION
Lipid metabolism disorders can cause a variety of problems.[1] Hyperlipidemia, which is characterized by elevated levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) and decreased levels of high-density lipoprotein cholesterol (HDL-C), has been considered an important globally public health problem.[2,3] Unhealthy dietary patterns with high-fat and high-calorie foods and drinks, gut microbiota disturbances, and genetic and environmental risk factors can lead to lipid profile abnormalities, atherosclerosis, and cardiovascular diseases.[4,5,6,7] There are various lipid-lowering drugs to prevent or treatment of subsequent diseases related to dyslipidemia.[8,9,10,11] Nowadays, using medicinal plants and traditional medicine have increased for prevention, promotion, and rehabilitation of noncommunicable diseases.[12] There are some functional foods such as some edible mushrooms with some bioactive compounds and antioxidant activities which could be considered as a nutritional strategy for preventing and treatment of hyperlipidemia. Edible mushrooms have high amounts of fiber, protein, micronutrients, and low amounts of fat.[13,14,15]
Ganoderma lucidum (G. lucidum), known commercially as “Lingzhi” or “Reishi,” is one of the most popular edible mushrooms in the world which has various pharmacological components such as triterpenoids, polysaccharides, peptides, ganoderic acids, steroids, and sterols.[16,17] It has been extensively used in traditional Chinese medicine that has a wide range of beneficial effects on improving different diseases including hepatitis, cancer, hypertension, hypercholesterolemia, diabetes, arthritis, and asthma. It has very low toxicity and without side effects.[18,19,20,21] Recently, some animal studies have investigated the lipid-lowering effects of G. lucidum and have shown contradictory results.[22] Some animal studies reported significant lipid-lowering effects of G. lucidum,[15,23] while others did not report any significant beneficial effects.[24]
Due to increasing interest in using G. lucidum as an adjunctive strategy for treatment dyslipidemia, the presence of inconsistent results of previous studies, insufficient human studies, and lack of comprehensive systematic review or meta-analysis, this study was designed to investigate the effects of G. lucidum on lipid parameters in animal studies with RCTs design.
MATERIALS AND METHODS
The current systematic review and meta-analysis study were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA) statement.[25] The protocol was registered on PROSPERO (ID: CRD42021225476)
Search strategy
A comprehensive literature search was conducted in Medline database (PubMed), Scopus, Web of Science, Cochrane Library, and Google Scholar up to the end of January 2022 using the following search terms (“Ganoderma” OR “G. lucidum”) and (“blood lipid” OR “lipid profile” OR “blood cholesterol” OR “dyslipidemia” OR “hypercholesterolemia” OR “LDL-C” OR “LDL” OR “HDL-C” OR “HDL” OR “TC” OR “TG” OR “TG”) The references of related review articles were checked to find undetected appropriate studies. The search strategy for each database is shown in Supplementary Table 1.
Supplementary Table 1:
Search strategy for each database
| Database | Search strategy |
|---|---|
| PubMed | #1 “Ganoderma“ [MeSH Terms] OR “G.lucidum” [ti, ab] OR “ Ganoderma lucidum“ [ti, ab] #2 “blood lipid“ [ti, ab] OR “lipid profile”[ti, ab] OR “blood cholesterol”[ti, ab] OR “dyslipidemia”[MeSH Terms] OR “hypercholesterolemia”[MeSH Terms] OR “low-density lipoprotein cholesterol”[ti, ab] OR “ Cholesterol, LDL”[MeSH Terms] OR “LDL”[ti, ab] OR “high-density lipoprotein cholesterol”[ti, ab] OR “ Cholesterol, HDL”[MeSH Terms] OR “HDL”[ti, ab] OR “total cholesterol”[ti, ab] OR “triglycerides”[MeSH Terms] OR “TG”[ti, ab] #1 AND #2 |
| Scopus | #1 “Ganoderma” [ti, ab, kw] OR “G.lucidum” [ti, ab, kw] OR “ Ganoderma lucidum” [ti, ab, kw] #2 “lipid profile”[ti, ab, kw] OR “blood cholesterol”[ti, ab, kw] OR “dyslipidemia”[ti, ab, kw] OR “hypercholesterolemia”[ti, ab, kw] OR “low-density lipoprotein cholesterol”[ti, ab, kw] OR “LDL”[ti, ab, kw] OR “high-density lipoprotein cholesterol”[ti, ab, kw] OR “HDL”[ti, ab, kw] OR “total cholesterol”[ti, ab, kw] OR “triglycerides”[ti, ab, kw] OR “TG”[ti, ab, kw] #1 AND #2 |
| Cochrane library | #1 “Ganoderma” [ti, ab, kw] OR “G.lucidum” [ti, ab, kw] OR “ Ganoderma lucidum” [ti, ab, kw] #2 “lipid profile”[ti, ab, kw] OR “blood cholesterol”[ti, ab, kw] OR “dyslipidemia”[ti, ab, kw] OR “hypercholesterolemia”[ti, ab, kw] OR “low-density lipoprotein cholesterol”[ti, ab, kw] OR “high-density lipoprotein cholesterol”[ti, ab, kw] OR “total cholesterol”[ti, ab, kw] OR “triglycerides”[ti, ab, kw] #1 AND #2 |
| Web of Science | #1 “Ganoderma” [topic] OR “G.lucidum” [topic] OR “Ganoderma lucidum” [topic] #2 “lipid profile”[topic] OR “blood cholesterol”[topic] OR “dyslipidemia”[topic] OR “hypercholesterolemia”[topic] OR “low-density lipoprotein cholesterol”[topic] OR “high-density lipoprotein cholesterol”[topic] OR “total cholesterol”[topic] OR “triglycerides”[topic] #1 AND #2 |
| Google Scholar | ((“Ganoderma” OR “G.lucidum” OR” Ganoderma lucidum”) AND (“lipid profile” OR “blood cholesterol”OR “dyslipidemia” OR “hypercholesterolemia” OR “low-density lipoprotein cholesterol” OR “high-density lipoprotein cholesterol” OR “total cholesterol” OR “triglycerides”)) |
Inclusion criteria
Animal studies with randomized controlled trials (RCTs) design, including cluster RCTs and randomized cross-over trials, were included. The English language studies that assessed the effects of G. lucidum on lipid profiles including TC, TGs, HDL-C, or LDL-C were selected.
Excluded criteria
Observational studies, human or in vitro studies, duplicated articles, and studies with insufficient data were excluded from the study.
Data extraction
Two independent reviewers (MA and MHB) reviewed and screened the published papers based on title, abstract, and full text. Any disagreement related to eligible records was resolved by the third reviewer (RK).
If the article and data were not available, we emailed the corresponding author and requested to send the article. The following data were extracted from relevant studies: first author's name, year of publication, study design, study duration, species and sex, number of animal in each group, type of G. lucidum, dose of G. lucidum supplementation, and mean of levels of TG, TC, LDL-C, and HDL-C before and after the intervention.
Quality assessment
The quality of included studies was assessed using The Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) tool by two independent reviewers (MA, PGh). Any discrepancy was resolved by third reviewer (MHB). The scale consists of 10 questions. Supplementary Table 2 shows the quality assessment of included studies.
Supplementary Table 2:
Characteristics of included studies
| Study reference year | Animal model | Dose of Ganoderma | Duration | Sex | Sample size | Lipid profile | Result |
|---|---|---|---|---|---|---|---|
| Adeyi A, 2021 | Rats | 26 mg/kg 44 mg/kg 70 mg/kg | 2 weeks | Male | 30 | TG, TC, HDL, LDL | Ganoderma (70 mg/kg body weight) showed, anti-dyslipidemia effects (TG, CHOL, LDL levels reduced dose dependently) were markedly (P<0.05) in a rat model of metabolic syndrome |
| Bach E, 2018 | Wistar rats | 1.00 mg/kg | 4 weeks | Male | 20 | TG, TC | Biochemical analysis also showed an effect of a decrease of total CHOL, triglycerides |
| Chen M, 2019 | Rats | 400 mg/kg | 4 weeks | Male | 16 | TG, TC, HDL, LDL | Ganoderma treatment reduced the levels of serum TC, TG, LDL, in T2DM rats. These results were consistent with a previous GLP administration which reduced serum TC, TG, LDL, levels in HFD-induced obesity mice |
| Elhussainy E, 2016 | Rats | 50 mg/kg 100 mg/kg | 8 weeks | Male | 40 | TG, TC, HDL, LDL | Treatment Ganoderma with low dose in diabetic rats significantly decrease the levels of serum TC, TG, LDL (P<0.01), and significantly increase the levels of HDL (P<0.05) compared to untreated diabetic rats. While with high dose in diabetic rats significantly decrease the levels of serum TC, TG, LDL (P<0.001), and significantly increase the levels of HDL (P<0.001) compared to STZ-induced diabetic rats |
| Eroglu H, 2018 | Wistar rats | 60 mg/kg 120 mg/kg 180 mg/kg | 3 weeks | Male | 60 | TG, TC, HDL, LDL | With the diabetic rats, the dose of 60, 120 and 180 mg/kg of Ganoderma effected in the increase of total TC, TG, VLDL, HDL levels, although it was not a significant change (P>0.05), instead, we observed a statistically significant decrease of LDL level (P<0.05) |
| Guo W, 2020 | Mice | 15 mg/kg 75 mg/kg | 8 weeks | Male | 40 | TG, TC, HDL, LDL | Supplementation with GA markedly reduced serum TG, TC and LDL levels in HFD-fed mice (P<0.05) but did not significantly increase the serum HDL-C level |
| Guo W, 2018 | Wistar rats | 150 mg/kg | 8 weeks | Male | 20 | TG, TC, HDL, LDL | Oral administration of GL95 markedly alleviated the dyslipidemia through decreasing the levels of serum TG, TC and LDL, and inhibiting hepatic lipid accumulation and steatosis. Consumption for 8 weeks significantly elevated the serum HDL level compared with the HFD and Sym groups (P<0.05) |
| Heriansyah T, 2015 | Wistar rats | 50 mg/kg 150 mg/kg 300 mg/kg | 12 weeks | Male/ female | 35 | TG, TC | G. lucidum PsP is beneficial in lowering the levels of lipid profiles TG and TC |
| Hu R, 2018 | Wistar rats | 150 mg/kg | 8 weeks | Male | 32 | TG, TC, HDL, LDL | The investigation of serum TG, TC, LDL, levels demonstrated that GL55 significantly improved these parameters compared with the HFD group |
| Li F, 2011 | Mice | 50 mg/kg 150 mg/kg | 4 weeks | Male | 32 | TG, TC, HDL, LDL | Supplementation resulted in lowering the TC, TG and LDL levels with elevation of HDL levels |
| Meng G, 2011 | Rats | 200 mg/kg 400 mg/kg 800 mg/kg | 16 weeks | Male/ female | 40 | TG, TC | GLP decrease TC and TG in high-fat fed/STZ diabetic rats. In the DC group, TC and TG were increased compared with the NC group. After treatment, TC and TG in the GLP-M or GLP-H group were reversed to the value that was significantly lower than that in DC group |
| Oluba M,2010 | Wistar rats | 100 mg/kg 200 mg/kg | 4 weeks | Male | 60 | TG, TC, HDL, LDL, VLDL | It is observed that the extract produced a significant decrease in serum TG, TC, VLDL and LDL- in normal rats and STZ-diabetic rats. In addition, serum HDL was significantly increased in STZ-diabetic rats given 200 mg/kg of the extract at the end of the 4th week |
| Pan D, 2014 | Mice | 75 mg/kg 250 mg/kg 450 mg/kg | 8 weeks | Male | 60 | TG, TC, HDL, LDL | TG and TC were significantly decreased by 47.8% (P<0.01) and 41.0% (P<0.01) for high dose, compared with those for the control. Furthermore, the serum LDL levels for both middle and high-dosage of FYGL treated mice were significantly (P<0.01) lower than those for control group, whereas the serum HDL level for those nutritional supplement-treated groups were higher (P<0.01) than that for control group |
| Pan R, 2021 | Mice | 100 mg/kg 400 mg/kg | 8 weeks | Male | 24 | TG, TC, HDL, LDL | The concentration of TC, TG, LDL in the wildtype (P<0.001), GLP (P<0.01) and MET groups (P<0.01) were significantly lower compared with the model control group. Additionally, the concentration of HDL in the serum of mice in the wildtype (P<0.001), GLP (P<0.001 or P<0.05) and MET groups (P<0.01) was significantly higher compared with the model control group |
| Sargowo D, 2015 | Rats | 50 mg/kg 150 mg/kg 300 mg/kg | 5 weeks | Male | 25 | TG, TC, HDL, LDL | PsP treatment decreased CHOL total level [Tabel 1] and increased HDL level significantly (P=0.04 and P=0.002 respectively) at PsP dose 50, 150, 300 mg/kg BW, but there is no correlation with LDL and triglyceride level (P=0.129 and P=0.340) |
| Sargowo D, 2017 | Wistar rats | 50 mg/kg 150 mg/kg 300 mg/kg | 12 weeks | Male/ female | 35 | TG, TC, HDL, LDL | The administration of G. lucidum PsP to diabetic model rats provided a significant difference in lowering foam cell (P=0.017; CI 95%). It also gave significant difference between levels of each lipid components (TC, TG, LDL and HDL) in at least two treatment groups (P=0.010; CI 95%) |
| Sarker M, 2015 | Rats | 200 mg/kg 400 mg/kg 600 mg/kg 800 mg/kg | 7 days | Male | 55 | TG, TC, HDL, LDL | With GLPEE (800 mg/kg) significantly reduced TC (P<0.001), TG (P<0.001) and LDL (P<0.001) levels, HDL level was significantly increased (P<0.01) compared to diabetic control rats. Similarly, GL-ME significantly reduced TC, TG and LDL and increased HDL levels compared to untreated diabetic rats. Overall, the effect of GL-PEE was comparatively better than of GL ME |
| Seto S, 2009 | Mice | 0.03 g/kg 0.3 g/kg | 4 weeks | Female | TG, TC, HDL, LDL | There was no apparent difference in TG levels measured between + db/+ m and + db/+ db mice (P>0.05), and G. lucidum consumption failed to alter the TG. In contrast, there was a higher level of TC and LDL (and a lower level of HDL in + db/+ db mice, compared to + db/+ m mice. G. lucidum consumption failed to modify TC, HDL and LDL levels measured in + db/+ m mice. In + db/+ db mice, G. lucidum (0.3 g/kg) reduced the LDL-CHOL level and the atherogenic index TC/LDL, compared to controls (P<0.05) | |
| Sharma P, 2019 | Mice | 50 mg/kg 100 mg/kg 200 mg/kg 500 mg/kg 1000 mg/kg | 1 weeks 90 days | Male/ female | 100 | TG, TC | CR-induced elevated levels of TC, TG were dose dependently reduced with GLAQ and effects were better in comparison to positive control (gallic acid). But with extract treatment the levels of TG, and TC were normalized to control levels |
| Tong C, 2008 | Rats | 0.1% | 6 months | Male | 24 | TG, TC, HDL, LDL | Supplementation of the feed with G. lucidum (0.1%) in rats decreased the TC, TG and LDL level significantly (P<0.05) while further increased the plasma concentration of HDL. In the case of rats fed with diet containing a mixture of 1% CHOL and 0.1% of Ganoderma, the lipid profile showed much higher readings (P<0.05) compared to the chol group. This seemed to indicate the possible hypocholesterolemic effect of G. lucidum in reducing the deposition of CHOL on the wall of the blood vessels |
| Tseng H, 2018 | Mouse | 150 mg/kg 300 mg/kg | 12 weeks | Male | TG, TC, LDL | Ganoderma had beneficial effects on lipid profiles | |
| Wang F, 2015 | Rats | 1 g/day | 4 weeks | Male | 24 | TG, TC, HDL, LDL | Following the therapeutic treatment of GLSP, the blood TG fell significantly by 49.0% and TC reduced by 17.8%, respectively, as compared to the nontreatment group. This study found that G. lucidum intervention could significantly enhance level HDL by 48.6% (P<0.01) compared to the model control. It is interesting to note that there was no significant difference in HDL between normal group and GLSP intervention group (P=0.6850) |
| Wang C, 2012 | Mice | 75 mg/kg 225 mg/kg | 4 weeks | Male | TG, TC, HDL, LDL | TG, TC, LDL and HDL levels were significantly decreased by 52.8% (P<0-01), 65.9% (P<0-001), 75.2% (P<0-001) and 41.7% (P<0-05), respectively, in db/db diabetic mice treated with a high dose of FYGL, compared with those for the diabetic control, and the potency of FYGL was dose-dependent | |
| Wihastuti T, 2016 | Wistar strain | 300 mg/kg/h 600 mg/kg/h 1200 mg/kg/h | 90 days | Male/ female | 80 | TG, TC, HDL, LDL | The examination showed not significant at the lipid profile (TC, TG, HDL, and LDL) and leukocytes |
| Chen, 2008 | Weanling piglets | 0 (control), 50, 100 and 150 mg/kg feed | 2 and 4 weeks | - | 72 | TG, TC | Ganoderma had not significant beneficial effects on lipid profiles |
| Hikino H, 1989 | Mice | 100 mg/kg | 5 h | Male | - | TG, TC | Ganoderma had not significant beneficial effects on lipid profiles |
| Huang, 2020 | SD rats | 1% or 3% freeze-dried G. lucidum | 5 weeks | Male | 48 | TBARS, a marker for lipid peroxidation, were reduced | |
| Lai P, 2020 | Japanese white rabbits | 6, 24, 96 mg/kg G. lucidum spore (EEG) | 4, 8 and 14 weeks | Male | 54 | TG, TC, LDL-C, HDL-C | Significantly reduced serum TG, TC and LDL-CHOL levels. Serum TC/HDL-CHOL values of rabbits were significantly lower |
| Li lu, 2019 | Kunming mice | 25, 50, and 100 mg/kg/day | 4 weeks | Male | 48 | MDA content significantly decreased it suggest that Ganoderma atrum PSG can significantly alleviate STZ-induced lipid peroxidation in the pancreas of diabetic animals | |
| Li NH, 2020 | C57BL/KsJ-db/ db mice and wild-type C57BL6/J mice | 100, 400 mg/kg/day | 8 weeks | Male | 24+6 | TC, TG, LDL-C, HDL-C | Lipid profiles significantly upregulated in db/db mice |
| Liang Z, 2018 | C57BL/6 mice | 200, 400 mg/kg/day | 12 weeks | Male | 100 | TC, TG, LDL-C, HDL-C | Effectively increased HDL-C levels and decreased TG, TC and LDL-C levels in the serum |
| Liu Y, 2019 | SD rats | 0.4 g/kg/BW | 5 weeks | Male | 60 | TC, TG, LDL-C, HDL-C | TC, TG and LDL-C levels of the intervention groups were significantly lower and HDL-C is significantly higher |
| LIU Y, 2015 | Chinese Holstein cows | 33, 67, 100 g/cow/day | 60 days | Female | 40 | TC, TG | TG contents were significantly different between control and the experimental groups but TC was not significantly different between the experimental groups and control |
| Majagi, 2009 | Rats of Wistar strain | 146, 243 mg/kg | 24 h | Male | 30 | TG, TC, HDL, LDL, VLDL | Mycelium product significantly (P<0.05, P<0.01) raised the HDL and significantly (P<0.01) lowered TC, LDL, TG and VLDL. But fruit body product has no significant effect on TG and VLDL |
| Menses, 2016 | C57BL/6 mice | GL low dose (0.5%)/ GL high dose (1.0%) | 43 days | Male | 56 | TC, TG, LDL-C | The addition of GL extracts to the diet significantly reduced serum TC and TG. The reduction in TC was accompanied by a decrease in the LDL-C concentration |
| Rubel R, 2010 | Swiss mice | Basal chow was supplemented with 85, 50, or 10% of G. lucidum CG 144 dried spawn | 12 weeks | Female | 54 | TG, TC, HDL, LDL, VLDL | Except TC G. lucidum is significantly effective on lipid profiles |
| Sakib H, 2018 | Wistar rats | 100 mg/kg BW/day | 28 days | Male | 42 | TC, TG, HDL-C, LDL-C | CF+GL significantly decrease TG but no significant effect on TC, HDL-C, LDL-C |
| Wihastuti, 2019 | Wistar rats | 50 mg/kg BW, 150 mg/kg BW, and 300 mg/kg BW | 30 days | 25 | TG, TC | Significantly decrease TG and TC | |
| Xiao, 2018 | C57BL/6 mice and C57BL/6 db/db mice | 50 mg/kg/day | 6 weeks | Male | 24 | TC, TG, HDL-C, LDL-C | Significant effect on TC, HDL-C, LDL-C and no significant effect on TG level |
| Xiao H, 2020 | SD rats | 0.05, 5 mg/kg rLZ-8 | 12 weeks | Male | 32 | TC, TG | An increase in serum levels of TC, TG and HbA1c in STZ model group was observed |
| Xu Y, 2019 | Kunming mice | 50, 100, 200 mg/kg body weight | 30 days | Male | 70 | TC, TG, HDL-C, LDL-C | Significantly effects on TC, TG, HDL-C, LDL-C |
| Yang BK-2002 | SD rats | 100 mg/kg BW | 4 weeks | Male | 32 | TC, TG, LDL-C | Significantly effects on TC, TG, LDL-C |
| Yang BK, 2004 | SD rats | 100 mg/kg BW | 2 weeks | Male | 32 | TC, TG, LDL-C | Significantly effects on TC, TG, LDL-C |
| Yang Q, 2010 | Wistar rats | 100, 200, or 300 mg/kg | 40 days | 40 | TC, TG | Oral administration of the polysaccharides extract for 40 days resulted in a dose-dependent significant reduction of the levels of fasting blood glucose, TC and TG | |
| Yang Z, 2017 | WT C57BL/6 mice and obese C57BL/6 (ob/ob) mice | 150, 300, 400 mg/kg | 4 weeks | Male | 10+50 | Lipid (Pg/mL) | Serum lipid level was reduced significantly after treatment with FYGL for 4 weeks |
| Zheng J, 2012 Zhong, 2018 | SD rats ob/ob mice on a C57BL6/J genetic background and C57BL6/J wild-type littermates | 200 mg/(kg BW) 100 mg/kg/day | 8 weeks 4 weeks | Male Male | 50 | TC, TG TC, TG, HDL-C, LDL-C | Significantly effects on TC, TG Significant effect on TC, HDL-C, LDL-C and TG |
| Zhu J, 2018 | Mice | 25 or 50 mg/kg/day GAA | 6 weeks | 48 | TC, TG, HDL-C, LDL-C | The serum TC, TG, LDL-C were largely reduced. HDL-C was markedly increased in GAA | |
| Zhu K, 2013 | Wistar rats | 200 mg/kg BW and 400 mg/kg BW | 4 weeks | Male | 60 | TC, TG, HDL-C, LDL-C | Administration of PSG-1 for 4 weeks to type 2 diabetic rats resulted in significant diminution of elevated TC, TG and LDL-C levels. Treatment with PSG-1 at 400 mg/kg BW showed a higher reduction of TC, TG and LDL-C levels in un-treated diabetic rats than PSG-1 at 200 mg/kg BW and 1, 1-dimethylbiguanide hydrochloride. Moreover, treatment of the diabetic rats with PSG-1 produced a significant increase in HDL-C levels |
CHOL: Cholesterol, GAA: Ganoderic acid A, WT: Wild type, SD: Sprague-Dawley, PSG: Polysaccharide, TG: Triglycerides, TC: Total CHOL, LDL: Low-density lipoprotein CHOL, HDL: High-density lipoprotein CHOL, VLDL: Very LDL, EEG: Ethanol extract, HbAIC: Hemoglobin A1c, G. lucidum: Ganoderma lucidum, HFD: High-fat diet, T2DM: Type 2 diabetes mellitus, GLP: Glucagon-like peptide 1, GA: Glycated albumin, PsP: Polysaccharide peptide, DC: Diabetic control, NC: Normal control, BW: Body weight, CI: Confidence interval, GLSP: G. lucidum spore powder, GL: Glycemic load, CF: Carbofuran, TBARS: Thiobarbituric acid-reactive substance, MDA: Malondialdehyde, STZ: Streptozocin, GLPEE: Ganoderma lucidum Petroleum ether extract, GL-ME: Ganoderma lucidum Methanol extract, GLAQ: Aqueous extract of Ganoderma lucidum, FYGL: Fudan-Yueyang- Ganoderma lucidum, MET: Melbine
Statistical analysis
The mean changes in lipid profiles before and after the administration of G. lucidum between groups of treatment and control were extracted from included studies. The effect size of standardized mean difference (SMD) was calculated by dividing the mean difference of lipid profiles between treatment and control groups by its standard deviation. The potential heterogeneity across studies was assessed using Cochran's Q-test and expressed using the I2 index. A random-effects model was used to estimate the SMDs. Subgroup analyses based on disease status (hyperlipidemic, diabetic, and healthy animals), dose of G. lucidum (<75, 75–150, 150–300, > =300 mg/kg), and gender of animals (male, female, and both) were performed to seek the sources of heterogeneity. In addition, meta-regression was used for assessing continuous variables including dose of G. lucidum, mean age, treatment duration, sample size, and year of publication of studies, to find the possible source of heterogeneity. The sensitivity analyses were performed by excluding one or several studies at a time to gauge the robustness of our results. Publication bias was evaluated by Funnel plot and Egger's test. All statistical analyses were conducted using the software STATA 12.0 (STATA Corp, College Station, Texas, USA).
RESULTS
Study selection
The flow diagram for the process of study selection is shown in Figure 1. The initial search recognized 358 articles and 226 of them remained after excluding duplicates. After screening the title and abstracts, 127 articles were excluded, and 99 articles remained for further assessment. The full texts of the remaining studies were reviewed carefully by two researchers. Any discrepancy was resolved by the third reviewer. Finally, 49 articles were included in the systematic review and meta-analysis. Characteristics of included studies are shown in Supplementary Table 2. Quality assessment of included studies is shown in Supplementary Table 3.
Figure 1:
Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart of study selection process
Supplementary Table 3:
Quality assessment of included studies
| Author, year | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
|---|---|---|---|---|---|---|---|---|---|---|
| Adeyi A, 2021 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Bach E, 2018 | Yes | Unclear | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Chen M, 2019 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Elhussainy E, 2016 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Eroglu H, 2018 | Yes | Unclear | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Guo W, 2020 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Guo W, 2018 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Heriansyah T, 2015 | Yes | Unclear | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Hu R, 2018 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Li F, 2011 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Meng G, 2011 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Oluba M, 2010 | Yes | Unclear | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Pan D, 2014 | Yes | Unclear | Unclear | Yes | Yes | Unclear | Unclear | Yes | Yes | No |
| Pan R, 2021 | Yes | Unclear | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Sargowo D, 2015 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Sargowo D, 2017 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Sarker M, 2015 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Seto S, 2009 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Sharma P, 2019 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Tong C, 2008 | Yes | Unclear | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Tseng H, 2018 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Wang F, 2015 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Wang C, 2012 | Yes | Unclear | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Wihastuti T, 2016 | Yes | Unclear | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Chen, 2008 | Yes | Yes | Unclear | Unclear | Unclear | Unclear | Unclear | Yes | Yes | No |
| Hikino H, 1989 | Unclear | Unclear | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Huang, 2020 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Lai P, 2020 | Yes | Yes | Unclear | Yes | Yes | Unclear | Unclear | Yes | Yes | No |
| Li lu, 2019 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Li NH, 2020 | Yes | Yes | Unclear | Yes | Yes | Unclear | Unclear | Yes | Yes | No |
| Liang Z, 2018 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Liu Y, 2019 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| LIU Y, 2015 | Yes | Yes | Unclear | Unclear | Unclear | Unclear | Unclear | Yes | Yes | No |
| Majagi, 2009 | Yes | Unclear | Unclear | Unclear | Yes | Unclear | Unclear | Unclear | Yes | No |
| Menses, 2016 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Unclear | Yes | No |
| Rubel R, 2010 | Yes | Unclear | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Sakib H, 2018 | Yes | Yes | Unclear | Yes | Yes | Unclear | Unclear | Yes | Yes | No |
| Wihastuti, 2019 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Xiao, 2018 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Xiao H, 2020 | Yes | Yes | Unclear | Yes | Yes | Unclear | Unclear | Yes | Yes | No |
| Xu Y, 2019 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Yang BK, 2002 | Yes | No | Unclear | Unclear | Yes | Unclear | Unclear | Unclear | Yes | No |
| Yang BK, 2004 | Yes | Unclear | Unclear | Unclear | Yes | Unclear | Unclear | Unclear | Yes | No |
| Yang Q, 2010 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Yang Z, 2017 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Zheng J, 2012 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Unclear | Yes | No |
| Zhong, 2018 | Yes | Yes | Unclear | Yes | Yes | Unclear | Unclear | Yes | Yes | No |
| Zhu J, 2018 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
| Zhu K, 2013 | Yes | Yes | Unclear | Unclear | Yes | Unclear | Unclear | Yes | Yes | No |
Influence of Ganoderma lucidum on lipid profiles
Table 1 shows estimated pooled SMD and 95% CI for the influence of G. lucidum on TG, TC, LDL-C, HDL-C, and very low-density lipoproteins (VLDL) between treatment and control groups. G. lucidum consumption was associated with decreased levels of TG, TC, LDL-C, and VLDL and was associated with increased levels of HDL-C. The pooled SMD was estimated negative and significant for TG (SMD = −1.52, 95% CI:-1.79, −1.24), TC (SMD = −1.51, 95% CI: −1.75, −1.27), LDL-C (SMD = −2.03, 95% CI: −2.37, −1.69) and VLDL (SMD = −1.06, 95% CI: −1.638, −0.482). Furthermore, the pooled SMD was estimated positive and significant for HDL-C (SMD = 1.03, 95% CI: 0.73, 1.33).
Table 1:
Estimated pooled standardized mean difference and 95% confidence interval for the influence of Ganoderma on lipid profiles
| Lipid profiles (mg/dL) | Number of study | Pooled SMD (95% CI) | P* | I2 (%) | P** | Egger | P*** | Number of filled studies | Pooled SMD (95% CI) |
|---|---|---|---|---|---|---|---|---|---|
| TG | 45 | -1.52 (-1.79-−1.24) | <0.001 | 83.80 | <0.001 | -4.73 | <0.001 | 3 | -1.57 (-1.86-−1.28) |
| TC | 43 | -1.51 (-1.75-−1.27) | <0.001 | 80.60 | <0.001 | -15.93 | <0.001 | 0 | - |
| LDL | 41 | -2.03 (-2.37-−1.69) | <0.001 | 84.60 | <0.001 | -13.67 | <0.001 | 0 | - |
| HDL | 46 | 1.03 (0.73-1.33) | <0.001 | 83.20 | <0.001 | 7.04 | <0.001 | 0 | - |
| VLDL | 6 | -1.06 (-1.638-−0.482) | <0.001 | 66.40 | <0.001 | -4.3 | 0.002 | 0 | - |
*P-value of pooled SMD, **P-value of Cochran's Q-test, ***P-value of egger test. TG: Triglycerides, TC: Total cholesterol, LDL: Low-density lipoprotein cholesterol, HDL: High-density lipoprotein cholesterol, VLDL: Very LDL, SMD: Standardized mean difference, CI: Confidence interval
For all lipid profiles, funnel plots were asymmetry [Supplementary Figures 1 (99.8KB, tif) -5 (89.5KB, tif) ], and Egger's tests were significant (P < 0.001). Therefore, there was publication bias among these studies. Trim and fill analysis was conducted. Only for TG levels, 3 studies were filled to adjust publication bias. The pooled SMD based on filled meta-analysis was estimated negative and significant (SMD = −1.57, 95% CI: −1.86, −1.28) but for other lipids, no study was filled. Hence, the publication bias had a non-significant effect on the results. The heterogeneity between studies was more than 80% for all lipid profiles except VLDL (I2 = 66.40%). Therefore, the subgroup analysis and meta-regression were used to explore the potential sources of heterogeneity. Results of subgroup meta-analysis according to disease status, dose of G. lucidum, and gender are presented in Tables 2-4. The pooled SMD showed G. lucidum was associated with decreased levels of TG, cholesterol, and LDL in hyperlipidemic and diabetic rats. The highest degree of effectiveness of G. lucidum was shown for LDL-C levels (SMD = −2.49, 95% CI: −3.01, −1.98) in diabetic rats. The pooled SMD showed G. lucidum was associated with increased levels of HDL-C levels in hyperlipidemic and diabetic rats. In healthy rats, the pooled SMD was negative and significant for TC and LDL-C. However, there was evidence of heterogeneity between the included studies. The heterogeneity between studies was more than 60% (P < 0.05).
Table 2:
Subgroup meta-analysis of pooled standardized mean difference and 95% confidence interval for the influence of Ganoderma on lipid profiles by disease status
| lipid profiles (mg/dL) | Number of studies | Pooled SMD (95% CI) | P* | I2 (%) | P** |
|---|---|---|---|---|---|
| TG | |||||
| Hyperlipidemic | 13 | -1.86 (-2.42-−1.31) | <0.001 | 81.40 | <0.001 |
| Diabetic | 30 | -2.04 (-2.46-−1.63) | <0.001 | 83.90 | <0.001 |
| Healthy | 12 | -0.31 (-0.63-0.01) | 0.059 | 67.50 | <0.001 |
| TC | |||||
| Hyperlipidemic | 13 | -1.91 (-2.44-−1.37) | <0.001 | 81.40 | <0.001 |
| Diabetic | 29 | -1.82 (-2.19-−1.44) | <0.001 | 81.40 | <0.001 |
| Healthy | 11 | -0.69 (-1.03-−0.35) | <0.001 | 70.40 | <0.001 |
| LDL | |||||
| Hyperlipidemic | 13 | -2.16 (-2.79-−1.53) | <0.001 | 85.10 | <0.001 |
| Diabetic | 20 | -2.49 (-3.01-−1.98) | <0.001 | 84.50 | <0.001 |
| Healthy | 8 | -0.74 (-1.27-−0.21) | 0.006 | 74.50 | <0.001 |
| HDL | |||||
| Hyperlipidemic | 11 | 1.41 (0.68-2.13) | <0.001 | 88.40 | <0.001 |
| Diabetic | 21 | 1.27 (0.89-1.66) | <0.001 | 79.90 | <0.001 |
| Healthy | 7 | 0.06 (-0.40-0.52) | 0.791 | 71.40 | <0.001 |
| VLDL | |||||
| Healthy | 3 | -0.72 (-1.52-0.08) | 0.078 | 64.30 | 0.024 |
*P-value of pooled SMD, **P-value of Cochran's Q-test. TG: Triglycerides, TC: Total cholesterol, LDL: Low-density lipoprotein cholesterol, HDL: High-density lipoprotein cholesterol, VLDL: Very LDL, SMD: Standardized mean difference, CI: Confidence interval
Table 3:
Subgroup meta-analysis of pooled standardized mean difference and 95% confidence interval for the influence of Ganoderma on lipid profiles by dose of Ganoderma
| Number of studies | Pooled SMD (95% CI) | P* | I2 (%) | P** | |
|---|---|---|---|---|---|
| TG (mg/dL) | |||||
| <75 mg/kg | 21 | -1.03 (-1.41-−0.64) | <0.001 | 67.60 | <0.001 |
| 75-150 mg/kg | 24 | -1.70 (-2.23-−1.17) | <0.001 | 82.50 | <0.001 |
| 150-300 mg/kg | 21 | -1.89 (-2.65-−1.13) | <0.001 | 88.30 | <0.001 |
| >300 mg/kg | 12 | -2.22 (-3.01-−1.43) | <0.001 | 88.90 | <0.001 |
| TC (mg/dL) | |||||
| <75 mg/kg | 21 | -1.34 (-1.70-−0.98) | <0.001 | 61.70 | <0.001 |
| 75-150 mg/kg | 23 | -1.80 (-2.30-−1.31) | <0.001 | 79.50 | <0.001 |
| 150-300 mg/kg | 20 | -1.87 (-2.56-−1.19) | <0.001 | 86.30 | <0.001 |
| >300 mg/kg | 11 | -1.86 (-2.55-−1.16) | <0.001 | 86.80 | <0.001 |
| LDL (mg/dL) | |||||
| <75 mg/kg | 15 | -1.72 (-2.32-−1.12) | <0.001 | 80.20 | <0.001 |
| 75-150 mg/kg | 16 | -2.90 (-3.68-−2.12) | <0.001 | 85.00 | <0.001 |
| 150-300 mg/kg | 13 | -1.89 (-2.63-−1.14) | <0.001 | 84.90 | <0.001 |
| >300 mg/kg | 9 | -2.86 (-3.86-−1.85) | <0.001 | 89.00 | <0.001 |
| HDL (mg/dL) | |||||
| <75 mg/kg | 15 | 0.45 (-0.15-1.05) | 0.14 | 83.50 | <0.001 |
| 75-150 mg/kg | 16 | 1.26 (0.69-1.83) | <0.001 | 81.80 | <0.001 |
| 150-300 mg/kg | 13 | 0.87 (0.22-1.52) | 0.009 | 83.60 | <0.001 |
| >300 mg/kg | 9 | 1.92 (1.02-2.81) | <0.001 | 88.20 | <0.001 |
| VLDL (mg/dL) | |||||
| 75-150 mg/kg | 3 | -0.78 (-1.42-−0.13) | 0.018 | 16.40 | 0.31 |
| 150-300 mg/kg | 3 | -1.58 (-3.09-−0.07) | 0.041 | 84.50 | <0.001 |
*P-value of pooled SMD, **P-value of Cochran's Q-test. TG: Triglycerides, TC: Total cholesterol, LDL: Low-density lipoprotein cholesterol, HDL: High-density lipoprotein cholesterol, VLDL: Very LDL, SMD: Standardized mean difference, CI: Confidence interval
Table 4:
Subgroup meta-analysis of pooled standardized mean difference and 95% confidence interval for influence of Ganoderma lucidum on lipid profiles by gender of rats
| lipid profiles (mg/dL) | Number of studies | Pooled SMD (95% CI) | P* | I2 (%) | P** |
|---|---|---|---|---|---|
| TG | |||||
| Male | 40 | -1.67 (-1.98-−1.35) | <0.001 | 82.90 | <0.001 |
| Female | 6 | -0.10 (-0.65-0.45) | 0.733 | 75.30 | <0.001 |
| TC | |||||
| Male | 38 | -1.76 (-2.07-−1.46) | <0.001 | 81.70 | <0.001 |
| Female | 5 | -0.37 (-0.70-−0.03) | 0.033 | 46.60 | 0.018 |
| LDL | |||||
| Male | 32 | -2.27 (-2.66-−1.89) | <0.001 | 85.60 | <0.001 |
| Female | 4 | -0.56 (-1.12-0.00) | 0.051 | 52.50 | 0.04 |
| HDL | |||||
| Male | 16 | 1.16 (0.84-1.49) | <0.001 | 83.30 | <0.001 |
| Female | 3 | -0.03 (-0.89-0.84) | 0.954 | 81.60 | <0.001 |
| VLDL | |||||
| Male | 3 | -1.02 (-1.72-−0.33) | 0.004 | 69.70 | <0.001 |
*P-value of pooled SMD, **P-value of Cochran's Q-test. TG: Triglycerides, TC: Total cholesterol, LDL: Low-density lipoprotein cholesterol, HDL: High-density lipoprotein cholesterol, VLDL: Very LDL, SMD: Standardized mean difference, CI: Confidence interval
The highest degree of effectiveness of G. lucidum was with doses >300 mg/kg (SMD = −2.22, 95% CI: −3.01, −1.43) on TG levels, 150–300 mg/kg (SMD = −1.87, 95% CI: −2.56, −1.19) and 75–150 mg/kg (SMD = −2.90, 95% CI: −3.68, −2.12) on LDL-C levels, >300 mg/kg (SMD = 1.92, 95% CI: 1.02, 2.81) and 150–300 mg/kg (SMD = −1.58, 95% CI: −3.09, −0.07) on VLDL levels. Furthermore, G. lucidum had the highest degree of effectiveness on LDL-C levels in male rats (SMD = −2.27, 95% CI: −2.66, −1.89). However, there was evidence of heterogeneity between the included studies (P < 0.05).
Results of meta-regression showed that there was a positive and significant association between mean age and duration of studies with pooled SMD of LDL-C and explain more than 83% of the heterogeneity between studies. Furthermore, the mean age and year of publication of studies contributed to the heterogeneity between studies related to HDL-C and VLDL levels, respectively [Table 5].
Table 5:
Results of meta-regression analysis for lipid profiles
| β (SE) | P | I2 (%) | |
|---|---|---|---|
| TG (mg/dL) | |||
| Dose (mg/kg) | -0.001 (0.001) | 0.55 | 83.98 |
| Sample size | -0.02 (0.05) | 0.666 | 83.71 |
| Year | 0.01 (0.05) | 0.769 | 83.90 |
| Age mean (weeks) | 0.07 (0.05) | 0.184 | 81.56 |
| Duration of intervention (weeks) | -0.01 (0.05) | 0.873 | 83.56 |
| TC (mg/dL) | |||
| Dose | -0.0003 (0.001) | 0.764 | 80.94 |
| Sample size | 0.07 (0.04) | 0.084 | 80.17 |
| Year | 0.01 (0.04) | 0.766 | 80.72 |
| Age mean (weeks) | 0.06 (0.04) | 0.106 | 76.27 |
| Duration of intervention (weeks) | 0.06 (0.04) | 0.13 | 80.78 |
| LDL (mg/dL) | |||
| Dose (mg/kg) | -0.0002 (0.001) | 0.865 | 84.81 |
| Sample size | -0.02 (0.06) | 0.715 | 84.53 |
| Year | 0.01 (0.07) | 0.841 | 84.76 |
| Age mean (weeks) | 0.13 (0.05) | 0.014 | 83.39 |
| Duration of intervention (weeks) | 0.14 (0.07) | 0.038 | 84.76 |
| HDL (mg/dL) | |||
| Does (mg/kg) | 0.002 (0.001) | 0.173 | 84.11 |
| Sample size | 0.03 (0.04) | 0.438 | 82.73 |
| Year | 0.003 (0.05) | 0.948 | 83.30 |
| Age mean (weeks) | -0.12 (0.06) | 0.046 | 86.04 |
| Duration of intervention (weeks) | -0.08 (0.05) | 0.111 | 83.28 |
| VLDL (mg/dL) | |||
| Dose (mg/kg) | -0.01 (0.01) | 0.22 | 72.05 |
| Sample size | 0.11 (0.07) | 0.128 | 62.46 |
| Year | 0.16 (0.06) | 0.026 | 46.64 |
| Age mean (weeks) | -2.27 (0.89) | 0.062 | 7.62 |
| Duration of intervention (weeks) | -0.07 (0.11) | 0.511 | 64.42 |
TG: Triglycerides, TC: Total cholesterol, LDL: Low-density lipoprotein cholesterol, HDL: High-density lipoprotein cholesterol, VLDL: Very LDL, SE: Standard error
DISCUSSION
The present meta-analysis study investigated the effects of G. lucidum on lipid parameters in animal models. According to our findings, G. lucidum has lowering effects on TG, TC, LDL-C, HDL-C, and VLDL levels. Different doses of G. lucidum have various degrees of effectiveness on lipid profiles.
Some mechanisms were suggested related to the effect of G. lucidum on lipid profiles. G. lucidum inhibits cholesterol synthesis in T9A4 hepatocytes and decreases cholesterol levels. G. lucidum reduces the activity of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase.[26]
G. lucidum influences the expression of some enzymes related to lipids including fatty acid synthase (FAS), acyl-CoA synthetase-1 (ACS1), fatty acid binding protein-4 (FABP4), and fatty acid transport protein-1 (FATP1).[27]
Studies on mice showed that G. lucidum extract could inhibit the increase of cholesterol and LDL levels by the reduction of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation in the liver.[28]
G. lucidum reduces the expression of sterol regulatory element-binding transcription factor 1 (SREBP1c), FAS, and ACC through a farnesoid X receptor and small heterodimer partner (FXR-SHP)-dependent mechanism and finally inhibits fatty acid synthesis and lipid droplets accumulation and the content of TG in the liver cell.[29]
Effect of Ganoderma lucidum on high-density lipoprotein cholesterol levels
Our results showed the beneficial effects of G. lucidum on HDL-C levels. However, some studies did not show any significant effect of G. lucidum on all lipid profiles[30,31,32,33] or only on HDL-C levels.[23,34,35,36,37,38,39] It seems that G. lucidum do not have significant effects on HDL-C levels in low doses and its effect becomes significant by increasing its dose.[40] Hence, it can be concluded that the method of purification is effective. There are different ways to use the active ingredient of G. lucidum. A traditional method of using G. lucidum is infusion with water and its powder. To achieve the maximum effect in this method, the cell walls must be completely destroyed during grinding. The most common method of purification is the use of ethanol and methanol. The use of different methods of consumption and purification, lack of knowledge about the dosage, and different quality of the consumed substance are the reasons of different results of studies.[41] It should be noted that in several articles, the use of G. lucidum, either in powder or purified form did not have significant adverse effects.[42,43]
Effect of Ganoderma lucidumon total cholesterol levels
Six studies reported no significant association between G. lucidum consumption and TC levels.[30,31,33,37,44,45] However, some studies showed significant beneficial effects of G. lucidum on TC levels.[34,35,36]
The reason for the contradiction between the results of the studies can be due to the following reasons. Rats do not have a gall bladder, so the access of the liver to unmodified cholesterol is limited as part of secreted substances to the intestine through bile and bile salt. In addition, high-fat diet was used in several studies which neutralized the effect of G. lucidum.[30]
Effect of Ganoderma lucidumon low-density lipoprotein cholesterol levels
Several studies showed the beneficial effects of G. lucidum on LDL-C levels. Four studies reported that G. lucidum had a non-significant effect on LDL-C along with other lipid profile components.[30,31,44,46]
Different purification methods, dosage and duration of G.lucidum consumption lead to various results in studies. 4 weeks’ intervention with G. lucidum reduced LDL-C by 44% while 8 weeks of intervention reduced LDL-C by 54%.[47]
Effect of Ganoderma lucidumon very low-density lipoproteins levels
Among the studies, only three studies investigated VLDL, one of which explicitly reported a significant effect of G. lucidum on VLDL levels[38] and another reported a significant effect only for mycelium products not fruitbody products of G. lucidum.[48] The third study showed that G. lucidum reduced the levels of VLDL. However, results were not significant.[37] The fruit body and mycelium product had hypoglycemic and hypolipidemic effects. However, it has a synergistic effect when taken together.[48]
Due to the limited number of studies, it is not possible to confidently comment on the effectiveness of G. lucidum and its mechanism on VLDL levels. It requires additional studies.
Effect of Ganoderma lucidumon triglyceride levels
Several studies showed G. lucidum consumption had a significant effect on TG levels.[34,35] Non-significant effect was reported in eight studies.[31,32,33,37,44,46,48,49] In seven of them non-significant effects were reported for other lipid profile components and in one study[49] it was reported only for TG levels.
In various studies, the intervention was done on healthy or unhealthy animals, but most of them reported the beneficial effects of G. lucidum on TG levels.
CONCLUSION
Meta-analysis of animal studies showed that G. lucidum had beneficial effects on lipid profiles. However, there are still many uncertainties about its mechanism and effects on metabolism. It is suggested that due to the absence of significant side effects regarding this type of mushroom and its beneficial effects, it can be used for the prevention or even treatment of abnormal lipid profiles.
Financial support and sponsorship
This study was conducted as the Project number 299201 supported by Isfahan University of Medical Sciences (Research Ethics code: IR.MUI.MED.REC.1399.957).
Conflicts of interest
There are no conflicts of interest.
Funnel plot of the effect of Ganoderma on total cholesterol. TC: Total cholesterol
Funnel plot of the effect of Ganoderma on triglyceride. TG: Triglyceride
Funnel plot of the effect of Ganoderma on low-density lipoprotein cholesterol. LDL: Low.density lipoprotein
Funnel plot of the effect of Ganoderma on high-density lipoprotein cholesterol. HDL: High-density lipoprotein
Funnel plot of the effect of Ganoderma on very low-density lipoproteins. VLDL: Very low-density lipoproteins
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Funnel plot of the effect of Ganoderma on total cholesterol. TC: Total cholesterol
Funnel plot of the effect of Ganoderma on triglyceride. TG: Triglyceride
Funnel plot of the effect of Ganoderma on low-density lipoprotein cholesterol. LDL: Low.density lipoprotein
Funnel plot of the effect of Ganoderma on high-density lipoprotein cholesterol. HDL: High-density lipoprotein
Funnel plot of the effect of Ganoderma on very low-density lipoproteins. VLDL: Very low-density lipoproteins