RESEARCH SHOWS THAT SOME MUSHROOMS MAY ENHANCE OUR DETOXIFICATION SYSTEM.
Our bodies are constantly barraged by environmental pollutants. Plasticizers penetrate our skin, the air we breathe contains dioxins and other carcinogens, halogenated hydrocarbons have been found in mother’s milk, and organic vegetables may contain heavy metals and other chemicals that damage our organs. We are certainly exposed to more toxins today than we were in the past, and sometimes the liver can’t keep up with the toxic load. Scientists are linking a variety of diseases to our chronic exposure to toxins including Alzheimer’s disease, cancer, and cirrhosis of the liver. Fortunately, certain food and supplements such as medicinal mushrooms may amplify the body’s detoxification system.
Reactive oxygen species (ROS) damage DNA and macromolecules including proteins and lipids. ROS cause mutations in DNA that can lead to a change in gene expression and render enzyme complexes useless. They are extremely harmful to cellular components, and many think that aging is largely a result of oxidative damage. To protect cells from ROS and other reactive molecules, certain enzymes are designed by the body to neutralize them. Some of the major antioxidant and detoxifying enzymes include catalase, glutathione-s-transferase, superoxide dismutase, and glutathione peroxidase. These enzymes not only change charged ROS to un-reactive water molecules, but they also neutralize and transform toxic chemicals into soluble molecules that can be excreted from the body. The detoxification system works like a bomb squad that deactivates explosive devices and turns land mines into tourist memorabilia.
If we consume a small amount of pesticide residue on an apple, these enzymes will attempt to neutralize it. Chronic consumption of toxins or exposure to a large dose can deplete these enzymes and make them unavailable to counteract oxidative attack. In fact, certain toxins affect the genes needed to express these enzymes, which limits their presence in the first place. ROS are especially harmful when enzymes are not present to neutralize them. For this reason it is important to maintain high levels of protective enzymes.
Multiple scientific studies have revealed that some varieties of mushrooms can protect the liver and stimulate the production of important detoxifying and antioxidant enzymes. It has been difficult for researchers to pinpoint the exact mechanisms involved, primarily because there are so many bioactive molecules in mushrooms. For instance, there are over 400 known bioactive molecules found in reishi mushrooms alone. Perhaps there is a synergistic effect, but more research is needed to be certain. Nonetheless, scientists have conducted studies with extracts from different fungi and have noticed significant detoxifying effects both in-vitro and in-vivo. Of the 400 bioactive compounds in reishi, a few have been isolated and have been shown to enhance the expression of genes upstream of important enzyme complexes.
According to a study published in the Journal of Food and Chemical Toxicology, a bioactive component of reishi, termed ganodermanondiol, positively influences the Nrf2 pathway to increase protective enzyme levels. Nrf2 has been viewed as one of the major signaling pathways that mediates the production of detoxifying and antioxidant enzymes. It’s like using a match to light a candle in a dark room. The candle is Nrf2 and the match is ganodermanondiol. If you light the candle, then you can find your way through the room. Other studies have been conducted using extracts from oyster and reishi mushrooms, although the researchers did not isolate specific bioactive molecules. A study published in the Journal of Experimental Gerontology demonstrated that oyster mushrooms have a similar effect as reishi mushrooms on the detoxification system. Rats fed with oyster mushrooms were found to have elevated levels of protective enzymes. In fact, aged rats supplemented with oyster mushroom extract were found to possess similar enzyme function when compared to young rats. The process of aging is typically associated with a decline in protective enzymes and increased oxidative stress, yet the consumption of oyster mushrooms was shown to counteract the effects of the typical aging process.
Some species of mushrooms may enhance the body’s ability to eliminate toxins and reduce oxidative stress. More research is required to understand the impact of each bioactive constituent, and there is little known about potential side effects. The consumption of mushrooms to neutralize toxins and ROS is not recommended or approved by the Food and Drug Administration.
Antioxidants: Molecules that undergo a reaction with oxidizing agents such as reactive oxygen species to prevent a reaction with other more-sensitive molecules. Free radicals can damage a cell or cellular components by transferring electrons to target molecules. Antioxidants provide a substrate for this transfer of electrons.
Dioxins: Common toxic pollutants that are produced during the incineration of waste, bleaching of paper, metal smelting, and synthesis of chemicals such as PCBs.
Enzyme: Proteins that catalyze reactions by lowering the amount of energy needed for a reaction to occur. If the reactions that take place in our bodies were to be repeated in the laboratory without the use of enzymes, many of them would require extremely high heat–energy. Enzymes are very efficient, produce no waste, and keep us alive.
Glutathione Peroxidase: A type of enzyme that transforms hydrogen peroxide into water and fatty radicals (lipid hydroperoxides) into soluble alcohols.
Glutathione-S-Transferase: An enzyme capable of changing charged toxins into neutral, soluble molecules. It can detoxify pesticides, herbicides, and a wide range of carcinogens.
Halogenated Hydrocarbons: A class of widespread toxins that are used as flame retardants, refrigerants, propellants, and solvents. They are known to degrade the ozone layer and have been found in mother’s milk. A type of halogenated hydrocarbon is released when depressing a canned-air container upside down.
Heavy Metals: A term generally used to describe metals that are known for their toxic effects. Many metal ions can become charged and become powerful oxidizing agents.
Reactive Oxygen Species: Reactive molecules that contain oxygen. Hydrogen peroxide and superoxides are commonly produced during cellular metabolism. These reactive oxygen species readily react with cellular components and can even lead to the death of a cell. Our immune system uses reactive oxygen species to kill invading microbial cells.
Oxidative stress: The condition that occurs when there is a lack of antioxidant enzymes to counteract the destruction of reactive oxygen species and other oxidizing agents. Maintaining high levels of antioxidant enzymes can prevent the effects of oxidative stress, which include cell death. Many think that aging is in part a result of oxidative stress.
Nrf2: The major pathway involved in expressing antioxidant enzymes. The Nrf2 pathway directly controls the production of protective enzymes and is seen as a potential target for medication designed to slow the aging process and prevent certain diseases. Mushrooms are thought to stimulate this pathway to positively affect the antioxidant defense system.
Plasticizers: Substances used to increase the flexibility and durability of plastics. They are also used in types of concrete and rubber. Phthalate esters are commonly used as plasticizers for the construction of PVC piping. Phthalates are known to be endocrine disruptors that can cause hormonal changes and birth defects.
Superoxide Dismutase: An enzyme that converts superoxides into oxygen and hydrogen peroxide. Functioning synergistically with glutathione peroxidase, these enzymes can effectively stabilize superoxides by converting them to water.
Selected Research and Highlights:
Li, B., Lee, D., Kang, Y., Yao, N., An, R., & Kim, Y. (2013). Protective effect of ganodermanondiol isolated from the Lingzhi mushroom against tert-butyl hydroperoxide-induced hepatotoxicity through Nrf2-mediated antioxidant enzymes. Food Chemistry and Toxicology, 53, 317-324.
“Ganodermanondiol, a biologically active compound, was isolated from the Lingzhi mushroom (Ganoderma lucidum). The present study examined the protective effects of ganodermanondiol against tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity. Ganodermanondiol protected human liver-derived HepG2 cells through nuclear factor-E2-related factor 2 (Nrf2) pathway-dependent heme oxygenase-1 expressions. Moreover, ganodermanondiol increased cellular glutathione levels and the expression of the glutamine-cysteine ligase gene in a dose-dependent manner. Furthermore, ganodermanondiol exposure enhanced the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and its upstream kinase activators, LKB1 and Ca2+/calmodulin-dependent protein kinase-II (CaMKII). This study indicates that ganodermanondiol exhibits potent cytoprotective effects on t-BHP-induced hepatotoxicity in human liver-derived HepG2 cells, presumably through Nrf2-mediated antioxidant enzymes and AMPK.”
“Previous phytochemical studies showed that Lingzhi mushrooms contain more than 400 bioactive compounds, including polysaccharides, triterpenoids, nucleotides, sterols, and steroids, which are generally considered the source of the mushroom’s biological activities and therapeutic uses.” (Boh et al., 2007 and Sanodiya et al., 2009)
“In the present study, we showed that ganodermanondiol significantly increased Nrf2 levels and efficiently promoted the translocation of Nrf2 into the nucleus in HepG2 cells This suggests that ganodermanondiol-induced HO-1 expression may occur via Nrf2 signaling pathway in HepG2 cells. In our previous study, we also demonstrated that sauchinone increases the cellular resistance of HepG2 cells to t-butyl hydroperoxide-induced oxidative injury, presumably through the p38 MAPK pathway-Nrf2/ARE-dependent HO-1 expression.” (Jeong et al., 2010)
Lin, W., & Lin, W. (2006). Ameliorative effect of Ganoderma lucidum on carbon tetrachloride-induced liver fibrosis in rats. World Journal of Gastroenterology, 12(2), 265-270.
“Oral administration of GLE significantly reduces CCl4-incluced hepatic fibrosis in rats, probably by exerting a protective effect against hepatocellular necrosis by its free-radical scavenging ability.”
Lakshmi, B., Ajith, T., Jose, N., & Janardhanan, K. (2006). Antimutagenic activity of methanolic extract of Ganoderma lucidum and its effect on hepatic damage caused by benzo[a]pyrene. Journal of Ethnopharmacology, 107(2), 297-303.
“The results indicated that the methanolic extract of Ganoderma lucidum occurring in South India possessed significant antimutagenic activity. The effect of B[a]P on hepatic enzymes, such as serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphtase (ALP), were also evaluated. The extract prevented the increase of SGOT, SGPT, and ALP activities consequent to B[a]P challenge, and enhanced the levels of reduced glutathione (GSH) and activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT). The extract also profoundly inhibited lipid peroxidation induced by B[a]P. The results revealed that Ganoderma lucidum extract restored antioxidant defense and prevented hepatic damage consequent to the challenge by B[a]P.”
Jayakumar, T., Aloysiusthomas, P., & Geraldine, P. (2007). Protective effect of an extract of the oyster mushroom, Pleurotus ostreatus, on antioxidants of major organs of aged rats. Experimental Gerontology, 42(3), 183-191.
“This study was undertaken to investigate the putative antioxidant activity of the oyster mushroom, Pleurotus ostreatus, on lipid peroxidation and antioxidant status of major organs of aged (24 month old) rats when compared to young (4 month old) rats. Elevated levels of malondialdehyde (MDA) and significantly lowered levels of reduced glutathione (GSH) and of vitamins C and E were observed in the liver, kidneys, heart and brain of aged rats when compared to values in young rats. Quantitative analysis of the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (Gpx) revealed significantly lower values in the liver, kidneys, heart, and brain of aged rats. An analysis of isozyme pattern of these enzymes in aged rats also revealed variations in relative concentration, presumably due to oxidative stress. Administration of the extract of P. ostreatus to aged rats resulted in elevated levels of reduced glutathione and vitamins C and E and in increased activities of CAT, SOD and Gpx so that the values in most of these parameters did not differ significantly from those in young rats. In addition, the level of MDA was lowered on administration of mushroom extract to aged rats. These results suggest that treatment with an extract of P. ostreatus can improve the antioxidant status during aging, therein minimizing the occurrence of age-associated disorders associated with involvement of free radicals.”
Sharma, R., Yang, Y., Sharma, A., Awasthi, S., & Awasthi, Y. (2004). Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis. Antioxidants and Redox Signalling, 6(2), 289-300.
“It has been known that glutathione S-transferases (GSTs) can reduce lipid hydroperoxides through their Se-independent glutathione peroxidase activity and that these enzymes can also detoxify lipid peroxidation end products such as 4-hydroxynonenal (4-HNE). In this article, recent studies suggesting that the Alpha class GSTs provide a formidable defense against oxidative stress are critically evaluated and the role of these enzymes in the regulation of oxidative stress-mediated signaling is reviewed. Available evidence from earlier studies together with results of recent studies in our laboratories strongly suggest that lipid peroxidation products, particularly hydroperoxides and 4-HNE, are involved in the mechanisms of stress-mediated signaling and that it can be modulated by the Alpha class GSTs through the regulation of the intracellular concentrations of 4-HNE.”
Hassan, Z., Elobeid, M., Virk, P., Omer, S., ElAmin, M., Daghestani, M., et al. (2012). Bisphenol A induces hepatotoxicity through oxidative stress in rat model. Oxidative Medicine and Cellular Longevity, 2012. Retrieved January 1, 2013, from http://www.ncbi.nlm.nih.gov/pubmed/22888396
“Reactive oxygen species (ROS) are cytotoxic agents that lead to significant oxidative damage. Bisphenol A (BPA) is a contaminant with increasing exposure to it (what does “it” refer to?) and exerts both toxic and estrogenic effects on mammalian cells. Due to limited information concerning the effect of BPA on liver, this study investigates whether BPA causes hepatotoxicity by induction of oxidative stress in liver. Rats were divided into five groups: The first four groups received oral administration of BPA 0.1, 1, 10, 50 (mg/kg/day) for four weeks. The fifth group was taken water with vehicle.The final body weights in the 0.1 mg group showed a significant decrease compared to control group. Significant decreased levels of reduced glutathione, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, and catalase activity were found in the 50 mg BPA group compared to control groups. A high dose of BPA (50 mg/kg) significantly increased the biochemical levels of ALT, ALP and total bilirubin. The BPA effect on the activity of antioxidant genes was confirmed by real time PCR in which the expression levels of these genes in liver tissue were significantly decreased compared to control. Data from this study demonstrate that BPA generates ROS and reduces the antioxidant gene expression that causes hepatotoxicity.”
Jayakumar, T., Sakthivel, M., Thomas, P., & Geraldine, P. (2008). Pleurotus ostreatus, an oyster mushroom, decreases the oxidative stress induced by carbon tetrachloride in rat kidneys, heart and brain. Chemico-Biological Interactions, 176(2-3), 108-120.
“Thus, the finding of this study shows that the administration of an extract of the oyster mushroom P. ostreatus appeared to protect the kidneys, heart, and brain of Wistar rats from CCl4-induced acute oxidative stress by reducing the intensity of lipid peroxidation and by enhancing the activities of enzymatic and non-enzymatic antioxidants. The observed alterations in the staining intensity of the isozymes of the antioxidant enzymes suggest the possible effect of P. ostreatus on the antioxidant defense system gene.”
“The present investigation is important in presenting data suggesting considerable promise for the mushroom P. ostreatus as a protective agent in an CCl4-induced damage on kidney, heart, and brain tissues.”
Shi, Y., Sun, J., He, H., Guo, H., & Zhang, S. (2008). Hepatoprotective effects of Ganoderma lucidum peptides against D-galactosamine-induced liver injury in mice. Journal of Ethnopharmacology, 117(3), 415-419.
“Ganoderma lucidum (GL), a traditional Chinese medicinal mushroom, has been widely used for the treatment of chronic hepatopathy of various etiologies. The hepatoprotective activity of peptides from Ganoderma lucidum (GLP) was evaluated against d-galactosamine (d-GalN)-induced hepatic injury in mice. GLP was administered via gavage daily for 2 weeks at doses of 60, 120, and 180 mg/kg respectively. Control groups were given the same amount of physiological saline synchronously. Then the mice from d-GalN control and GLP-treated groups were treated with d-GalN (750 mg/kg) suspended in normal saline by intraperitoneal injection. d-GalN-induced hepatic damage was manifested by a significant increase in the activities of marker enzymes (AST, ALT) in serum and MDA level in liver (P < 0.01), and by a significant decrease in activity of SOD and GSH level in liver (P < 0.01). Pretreatment of mice with GLP reversed these altered parameters to normal values. The biochemical results were supplemented by histopathological examination of liver sections. The best hepatoprotective effects of GLP were observed after treatment with the dose of 180 mg/kg as it was evidenced from biochemical parameters and liver histopathological characters, which were similar to those of normal control group. Results of this study revealed that GLP could afford a significant protection in the alleviation of d-GalN-induced hepatocellular injury.”
Mates, J. M., Segura, J. A., Alonso, F. J., & Marquez, J. (2010). Roles of dioxins and heavy metals in cancer and neurological diseases using ROS-mediated mechanisms. Free Radical Biology and Medicine, 49(9), 1328-1341. What do the [__] numbers in this paragraph and the ones following it refer to?
“Phase II enzymes and high intracellular levels of GSH play a prominent role in providing such protection. Hence, expression and induction of enzymes that metabolize xenobiotics, drugs, and carcinogens play an important role in determining the risk of cancer in humans . For instance, an increase in ROS and RNS may be the event that led to the consumption and reduction of salivary antioxidant systems, thus explaining the oxidatively damaged  DNA and proteins and possibly the promotion of oral squamous cell carcinoma in patients . Higher levels of oxidative stress have been also observed in the colorectal epithelium of premalignant adenoma cells , in the pathogenesis of breast cancer  and melanoma , as well as of many other cancer types ,  and .”
“Dioxins are not intentionally produced and have no known use. They are the by-products of various industrial processes (e.g., bleaching of paper pulp and the manufacture of chemicals and pesticides) and combustion activities (e.g., burning household trash, forest fires, and waste incineration). Dioxins are found at low levels throughout the world in air, soil, water, and sediment and in foods such as dairy products, meats, fish, and shellfish . The contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a prototype compound of a whole class of halogenated aromatic hydrocarbons termed dioxin-like contaminants present in food, human tissues, mothers’ milk, and environmental samples .”
“An increase in ROS has been seen when CRL-1439 normal liver cells were exposed to various concentrations of Cd(II). The metabolites GSH, GSSG (oxidized GSH), and total thiols showed a decrease in concentration. Equally, malondialdehyde showed an increase due to lipid peroxidation . In conclusion, cadmium destroys the antioxidant system, which diminishes the activities of SOD, CAT, and GPX, causing an increase in the lipid peroxidation level .”
“GSH inhibits free radical formation by copper ions in the presence of H2O2. Such protective effect was attributed to its ability to stabilize copper in the Cu(I) oxidation state, preventing redox cycling and the generation of ROS . Copper may be of particular importance in the induction of oxidative DNA damage. Cu2+ ions may undergo intercalation as well as complexation to purine bases. Therefore, Cu+ and Cu2+ ions present within cellular DNA may be involved in oxidatively generated DNA damage. Moreover, Cu2+, as a free ion or as part of complexes, generates 1O2 as the predominant reactive species upon reaction with H2O2.”
“Cellular oxidative stress is due to the production of ROS, on the one hand, and weaknesses of the antioxidative defense, on the other. This is particularly true for cells with an active metabolism such as neurons. Factually, the production of radicals is heightened in the brain because of the high oxygen metabolism of neurons  and . Oxidatively damaged DNA is increased in the brains of Parkinson’s patients and in spinal cord tissue of amyotrophic lateral sclerosis (ALS) patients .” “Although evidence supports a pathogenic role for oxidative stress in neurodegenerative diseases, the causes and consequences of ROS that promote oxidatively generated damage have not been directly demonstrated .”
“Some of the key mitochondrial enzymes have shown deficient activity in susceptible neurons, which may lead to increased ROS production . Phase II enzyme induction can prevent cell death in astrocytes exposed to high concentrations of peroxides . Mitochondrial H2O2, which has the ability to pass biological membranes, is not a highly reactive molecule; however, it can react with metals to produce •OH and 1O2 that can become highly detrimental to neurons .”
 Li, B., Lee, D., Kang, Y., Yao, N., An, R., & Kim, Y. (2013). Protective effect of ganodermanondiol isolated from the Lingzhi mushroom against tert-butyl hydroperoxide-induced hepatotoxicity through Nrf2-mediated antioxidant enzymes. Food Chemistry and Toxicology, 53, 317-324.
 Jayakumar, T., Aloysiusthomas, P., & Geraldine, P. (2007). Protective effect of an extract of the oyster mushroom, Pleurotus ostreatus, on antioxidants of major organs of aged rats. Experimental Gerontology, 42(3), 183-191.