Mushrooms & Diabetes

LEARN WHAT CURRENT RESEARCH SAYS ABOUT MUSHROOMS AND DIABETES.

MUSHROOMS AND DIABETES: WHAT RESEARCH REVEALS

According to the Center of Disease Control and Prevention[1], diabetes mellitus is a metabolic disease that affects 8.3% of the U.S. population (25.8 million people) and is the seventh leading cause of death. While type I diabetes is dictated by genetics, type II is acquired and can be prevented. Fats and carbohydrates are important for bodily function, but a diet in excess of either without regular exercise is a recipe for diabetes. Maintaining a healthy diet and exercising are the most important actions you can take to prevent diabetes, but research has also shown that consuming certain varieties of mushrooms can aid in retarding the onset of diabetes and can help by maintaining normal blood sugar levels in patients with diabetes.

It has long been known that type II diabetes is impacted by poor diet, but it was not until a few years ago that scientists uncovered the biochemical mechanism. Type II diabetes is marked by insulin resistance, which is a defense mechanism to prevent the damaging effects of over-nutrition. Insulin is the hormone responsible for regulating the use of fats and carbohydrates for cellular energy production. When we eat a cheeseburger, the chemical components are broken apart by acids and enzymes in our digestive system. The smaller fractions are circulated throughout the blood stream to reach different parts of the body. Insulin allows sugar to be withdrawn from the blood and internalized by cells to be used for energy production. Once inside the cell, simple sugars are fed through a few pathways, the last of which is the electron transport chain (ETC). The pathways prior to the ETC transform the sugars into new molecules, and during the process electrons are stripped and attached to carrier molecules. The electron carriers take the electrons and insert them into the ETC. The electrons are passed from one enzyme to the next, and each time a transfer is made, protons are pumped out across a membrane. Because positive protons are pumped out, the space outside of the membrane becomes positively charged and the space on the inside holds a negative charge. The difference in charge means that there is an electrochemical gradient on either side of the membrane. At the end of the chain, the final enzyme allows three protons to flow back across the membrane. The protons flow in and spin a rotor–mechanically–and this spinning action pushes two molecules together. The two molecules fuse to form ATP, which is the body’s major energy molecule. The process is analogous to a reservoir with a water turbine downstream. Protons are stored in the reservoir and released to spin a turbine that creates energy for the body.

For the ETC to function properly, ATP should be used when it is available, and nutrients (fats and sugars) should be fed into the upstream pathways only when there is a demand. If sufficient ATP is already available and the upstream pathways continue to be flooded with fats and sugars, problems arise. According to researchers at the Metabolic Institute for the Study of Diabetes and Obesity[2], consuming excess fats and sugars without depleting energy stores through exercise leads to the production of radical oxygen species that damage our cells. Overloading the ETC with electron carriers leads to the leaking of electrons from the chain. Electrons leak, bond with oxygen, and melt the intracellular components. Continued over-nutrition leads to the inhibition of the metabolic pathways. It is like a manufacturing assembly line with too many raw materials and not enough workers. If the assembly line is overflowing with materials, and the workers are being injured when the supplies fall off the line, the supervisor will hit the emergency stop button. The only problem is that the supervisor doesn’t stop the shipments from being received, so even though the assembly line stops functioning, the warehouse continues to fill with incoming shipments. Over-nutrition causes the body to ignore insulin; this is insulin resistance. It is a successful strategy for preventing the production of radical oxygen species, but if we continue to eat, our blood will become saturated with sugar (hyperglycemia) because we no longer have a method for processing and withdrawing this sugar from the bloodstream.

Eating less fat and sugar and exercising is without a doubt the best strategy for maintaining insulin sensitivity, but consuming certain mushrooms can help, too. Some species of fungi promote radical scavenging, reduce oxidative damage to cells, and therefore decrease the development of insulin resistance. Studies on mice have shown that the polysaccharides in turkey tail mushrooms promote superoxide dismutase activity, an important enzyme for eliminating superoxide radicals in the mitochondria–where the ETC occurs[3]. Researchers at the Amala Institute of Medical Sciences[4] have also found reishi mushrooms to decrease oxidative stress and ameliorate the functioning of the ETC when damaged by strong oxidants. According to a study published in the Journal of Food Chemistry[5], the ability of the polysaccharides in reishi mushrooms to reduce cellular oxidation can directly or indirectly raise insulin levels and decrease blood sugar. Shiitake mushrooms have also been found to counteract the oxidative effects of high-fat diets[6].

The antioxidant properties of mushrooms are of pharmacological interest because they target the problem at the source: inside of the mitochondria where the ETC is executed. Insulin resistance is in response to oxidative damage, and the polysaccharides in fungi minimize this damage. If insulin resistance ensues, blood sugar levels can reach dangerous levels. Mushrooms should certainly not be used to treat or prevent diabetes, but supplementing with certain species may aid in restoring insulin sensitivity and decreasing the effects of over-nutrition.

Key Terms:

ATP: Formally known as adenosine triphosphate. It plays a lot of different roles but is most commonly referenced as the “energy molecule” for its ability to transport chemical energy.

Blood Sugar Concentration: The amount of glucose in the blood. Glucose is fed into glycolysis to eventually yield large amounts of ATP at the end of the electron transport chain. Low blood sugar levels limit ATP synthesis, but high blood sugar poses its own set of problems.

Diabetes Mellitus Type II: An acquired form of diabetes that is defined by insulin resistance and high blood sugar levels caused by poor nutrition and lack of exercise. Recent research exposed that insulin resistance is actually a defense mechanism to prevent oxidative damage associated with over-nutrition.

Electrochemical gradient: A difference of electrical charge across a membrane.

Electrons: A constituent of atoms that holds a negative charge.

Electron Transport Chain: The pathway that humans rely on for generating ATP (chemical energy). Without the electron transport chain, we would need to rely on glycolysis for energy production, and would need to eat about half our weight in sugar each day. In the electron transport chain, electrons are passed from one enzyme complex to the next, with the final electron acceptor being molecular oxygen. With each transfer, protons are pumped to the other side of a membrane which generates an electrochemical gradient. At the end of the chain, the final enzyme is mechanically driven by allowing a flow-back of protons. The ATP synthase enzyme is the final enzyme, and it has a rotor that spins as the protons flow into the enzyme. The spinning pushes ADP up against a phosphate group and allows for the formation of ATP. The electron transport chain occurs in the inner membrane of the mitochondria.

Enzymes: 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.

Insulin: A hormone produced in pancreas that is responsible for regulating metabolism. The presence of insulin stimulates the transfer of glucose from the blood into the cell to be used for ATP synthesis. In the absence of insulin, glucagon (another enzyme) converts fat into energy. So with insulin, blood sugar is used for energy and without it, we burn fat.

Insulin Resistance: A defense mechanism to protect the mitochondria from oxidative damage. Insulin resistance means that even though insulin is present, blood sugar is not used for metabolism. Blood sugar levels continue to rise as if no insulin is present. Type II diabetes is marked by insulin resistance.

Mitochondria: An intracellular organelle typically referred to as the powerhouse of the cell. This is where we generate most of our energy–through the electron transport chain.

Over-nutrition: Flooding the body with fats and sugars when ATP stores are not being utilized. In other words, eating more calories than are being used.

Polysaccharides: Long chains of sugars. They can be complex and branched, or straight and comprised of one or more type of sugar.

Protons: A constituent of atoms that holds a positive charge.

Reactive Oxygen Species: Reactive molecules that can cause damage to our cells. Oxidative damage is thought by some to be the cause of aging. Superoxides and hydrogen peroxide are examples of reactive oxygen species.

Superoxide Dismutase: An enzyme that can convert highly reactive superoxides into hydrogen peroxide and oxygen. The hydrogen peroxide is then catalyzed further by other enzymes to convert it to water. Superoxide dismutase is an extremely important antioxidant molecule that prevents superoxides from damaging our cells.

Selected Research and Highlights:

Sudheesh, N., Ajith, T., Mathew, J., Nima, N., & Janardhanan, K. (2012). Ganoderma lucidum protects liver mitochondrial oxidative stress and improves the activity of electron transport chain in carbon tetrachloride intoxicated rats. Hepatology research : the official journal of the Japan Society of Hepatology, 42(2), 181-191.

“The mitochondrial reactive oxygen species level was enhanced and mitochondrial membrane potential was declined significantly. Administration of G. lucidum significantly and dose independently protected liver mitochondria.”

“Conclusion: The findings suggest that protective effects of G. lucidum against hepatic damage could be mediated by ameliorating the oxidative stress, restoring the mitochondrial enzyme activities and membrane potential.”

Fatmawati, S., Shimizu, K., & Kondo, R. (2011). Ganoderol B: a potent α-glucosidase inhibitor isolated from the fruiting body of Ganoderma lucidum. Phytomedicine, 18(12), 1053-1055.

“α-Glucosidase inhibitor has considerable potential as a diabetes mellitus type 2 drug because it prevents the digestion of carbohydrates. The search for the constituents reducing α-glucosidase activity led to the finding of active compounds in the fruiting body of Ganoderma lucidum. The CHCl3 extract of the fruiting body of G. lucidum was found to show inhibitory activity on α-glucosidase in vitro.”

“Carbohydrates (e.g. polysaccharides), the major components of our daily foods, are transformed into simple sugars and then absorbed through the intestine. α-Glucosidase (EC 3.2.1.20), an enzyme located in the small intestine epithelium, catalyzes the cleavage of disaccharides and oligosaccharides to glucose. α-Glucosidase inhibitor has been proposed as a treatment for diabetes mellitus type 2, since it works by preventing the digestion of carbohydrates. In actual fact, acarbose, known as α-glucosidase inhibitor, has been shown to inhibit the increase of the blood glucose level after meals and to diminish postprandial hyperglycemia and glycosylated hemoglobin (Martin and Montgomery 1996). In the course of our studies on anti-diabetic compounds made from natural products, we have found that the extract of G. lucidum has potent inhibitory activity against α-glucosidase.”

Ravi, B., Renitta, R., Prabha, M., Issac, R., & Naidu, S. (2013). Evaluation of antidiabetic potential of oyster mushroom (Pleurotus ostreatus) in alloxan-induced diabetic mice. Immunopharmacololgy and Immunotoxicology, 35(1), 101-109.

“The present investigation suggests that the edible mushroom P. ostreatus exhibits significant antihyperglycemic as well as antihyperlipidemic effects. Studies revealed that the ethanolic extract of P. ostreatus can be considered as an important addition to the therapeutic armamentarium for the treatment of diabetes.”

Handayani, D., Chen, J., Meyer, B. J., & Huang, X. F. (2011). Dietary shiitake mushroom (Lentinus edodes) prevents fat deposition and lowers triglyceride in rats fed a high-fat diet. Journal of Obesity, 2011, 1-8.

“This study also revealed the existence of negative correlations between the amount of Shiitake mushroom supplementation and body weight gain, plasma TAG, and total fat masses.”

“This study showed that adding HD-M in a high-energy diet containing 50% fat can significantly prevent total fat deposition and significantly lower plasma TAG in rats compared with no addition of Shiitake mushroom diet. It was also found that the plasma TAG-lowering effect was negatively associated with the amount of Shiitake mushroom supplementations and positively associated with the amount of visceral fat.”

Yang, J. P., Hsu, T., Lin, F., Hsu, W., & Chen, Y. (2012). Potential antidiabetic activity of extracellular polysaccharides in submerged fermentation culture of Coriolus versicolor LH1. Carbohydrate Polymers, 90(1), 174-180.

“Two first purified saponins fractions (ePS-F3-1 and ePS-F4-1) exhibited strong α-glucosidase inhibition and had a higher inhibitory activity than Krestin (PSK) and the crude ePS; ePS-F4-1 showed the best inhibition activity. Although a better structural analysis is required for the polysaccharides present in these fractions, the α-glucosidase inhibition activity may be contributed from the polysaccharides, triterpenoids, or polysaccharide mixture.”

“α-Glucosidase, one of the starch hydrolysis enzymes in our intestine, can hydrolyze starch to glucose and then absorb the glucose into intestinal micromodules. In our study, ePS-F3-1 and ePS-F4-1 from the culture medium of C. versicolor LH1 showed strong inhibition of α-glucosidase. Therefore, ePS-F3-1 and ePS-F4-1 can potentially provide antidiabetic activity after eating.”

Anderson, E. J., Wasserman, D. H., Woodlief, T. L., Boyle, K. E., Lustig, M. E., Neufer, P. D., et al. (2009). Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. Journal of Clinical Investigation, 119(3), 573-581.

“The generation of surplus reducing equivalents would in turn be expected to elevate the redox state of complex I and/or the ubiquinone pool. Under resting conditions, the rate of electron leak from complex I is extremely sensitive to redox state/membrane potential (37–40), such that even a small surplus of reducing equivalents would be predicted to elicit an exponential increase in the rate of superoxide production and H2O2 emission from mitochondria.”

“The implication is that mitochondrial dysfunction, similar to insulin resistance, is a consequence rather than a primary cause of the altered cellular metabolism that develops with nutritional overload.”

“The results of the present study suggest that the biological status of skeletal myofibers, including the degree of insulin sensitivity, is functionally linked to the redox state of the cell. With this mechanism, the reducing potential of the electron transport system provides a means for the cell to sense metabolic imbalance, while the emission of H2O2 from the mitochondria provides a means of initiating an appropriate counterbalance response — shifting the redox state and decreasing insulin sensitivity in an attempt to restore metabolic balance.”

“First, it is important to recognize that pharmacological approaches designed to improve insulin-stimulated glucose uptake without a corresponding increase in metabolic demand may exacerbate the underlying problem, pushing the intracellular redox environment further toward an oxidized state. Second, the present study demonstrates that the use of a mitochondrial-targeted antioxidant represents a potentially effective counterbalance strategy for treating insulin resistance and other diseases associated with chronic metabolic imbalance.”

Wei, W., Tan, J., Guo, F., Ghen, H., Zhou, Z., Zhang, Z., et al. (1996). Effects of Coriolus versicolor polysaccharides on superoxide dismutase activities in mice. Acta Pharmacologica Sinica, 17(2), 174-178.

“CVP exerted the favorable effects on SOD activities in mice. Coriolus versicolor polysaccharides (CVP) exert inhibitory effects on experimental and clinical tumors. These effects are presumed to be mediated mainly by host-defense mechanism, especially immunological responses. Superoxide dismutase (SOD) plays an important role in protecting cells against superoxide radical (O2-.) damages and over-production of O2-. or SOD abnormities (there is a word missing here – “that”?) exist in many diseases. The present study was to investigate if the CVP could exert some favorable effects on SOD activities in vivo.”

Boden, M., Brandon, A., Tid-Ang, J., Preston, E., Wilks, D., Stuart, E., et al. (2012). Overexpression of manganese superoxide dismutase ameliorates high-fat diet-induced insulin resistance in rat skeletal muscle. American Journal of Physiology Endocrinology and Metabolism, 303(6). Retrieved January 1, 2013, from http://www.ncbi.nlm.nih.gov/pubmed/22829583

“The HF diet significantly reduced whole body and TC muscle insulin action, whereas overexpression of MnSOD in HF diet animals ameliorated this reduction in TC muscle glucose uptake by 50% (P < 0.05). Decreased protein carbonylation was seen in MnSOD overexpressing TC muscle in HF-treated animals (20% vs. contralateral control leg, P < 0.05), suggesting that this effect was mediated through an altered redox state. Thus interventions causing elevation of mitochondrial antioxidant activity may offer protection against diet-induced insulin resistance in skeletal muscle.”

Hoehn, K. L., Richardson, A. R., Salmon, A. B., James, D. E., Cooney, G. J., Kraegen, E. W., et al. (2009). Insulin resistance is a cellular antioxidant defense mechanism. Proceedings of the National Academy of Sciences, 106(42), 17787-17792.

“These data place mitochondrial superoxide at the nexus between intracellular metabolism and the control of insulin action potentially defining this as a metabolic sensor of energy excess.

Mitochondrial oxidative species are primarily formed by the escape of high energy electrons from complex I and/or complex III of the electron transport chain (ETC). These electrons reduce molecular oxygen creating O2−. Inhibition of mitochondria superoxide production reverses IR in vitro.

“Findings show that many models of IR are associated with increased mitochondrial O2•−, which if reversed may restore insulin sensitivity.”

“The ratio between nutrient supply and ATP demand is at the center of this mechanism such that when this ratio is imbalanced, a rapid compensatory cellular response can acutely correct energy shortage or surplus by controlling glucose entry into the cell. It is well-accepted that when cellular nutrient supply/ATP demand is low (e.g., exercise or calorie restriction) the concomitant increase in the AMP/ATP ratio leads to activation of AMPK and subsequently the increase in glucose uptake independent of insulin. However, in the opposite situation, when nutrient supply/ATP demand is high (e.g., nutrient oversupply or inactivity) we propose that the ensuing increase in mitochondrial superoxide production is the signal that drives a cellular response to dampen glucose uptake via the antagonism of GLUT4.”

“In summary, the fact that mitochondrial O2− is upstream of IR is of major significance suggesting that IR may be part of the antioxidant defense mechanism to protect cells from further oxidative damage. Thus, IR may be viewed as an appropriate response to increased nutrient accumulation.”

Jia, J., Zhang, X., Hu, Y., Wu, Y., Wang, Q., Li, N., et al. (2009). Evaluation of in vivo antioxidant activities of Ganoderma lucidum polysaccharides in STZ-diabetic rats. Food Chemistry, 115(1), 32-36.

“Decreased level of serum insulin and increased level of blood glucose (BG) were observed in the plasma of untreated diabetic control rats. G. lucidum polysaccharides treatment significantly and dose-dependently increased nonenzymic and enzymic antioxidants, serum insulin level and reduced lipid peroxidation, and blood glucose levels in STZ-diabetic rats. From the present study, it can be concluded that G. lucidum polysaccharides can be considered as a potent antioxidant.”

Xu, C., Haiyan, Z., Jianhong, Z., & Jing, G. (2008). The pharmacological effect of polysaccharides from Lentinus edodes on the oxidative status and expression of VCAM-1mRNA of thoracic aorta endothelial cell In high-fat-diet rats. Carbohydrate Polymers, 74(3), 445-450.

“The result indicates that the administration of polysaccharides from L. edodes significantly reduced serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-c) and enhanced serum antioxidant enzyme activity and thymus and liver index in high-fat rats. In addition, the administration of polysaccharides from L. edodes significantly decreased the increased expression level of VCAM-1mRNA in group (V) (P < 0.05). In conclusion, our data suggest that the administration of polysaccharides from L. edodes could decrease the increased oxidation stress induced by a high-fat diet and decrease expression of VCAM-1mRNA of thoracic aorta endothelial cell in rats.”


[1] http://www.cdc.gov/features/diabetesfactsheet/

[2] Anderson, E. J., Wasserman, D. H., Woodlief, T. L., Boyle, K. E., Lustig, M. E., Neufer, P. D., et al. (2009). Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. Journal of Clinical Investigation, 119(3), 573-581.

[3] Yang, J. P., Hsu, T., Lin, F., Hsu, W., & Chen, Y. (2012). Potential antidiabetic activity of extracellular polysaccharides in submerged fermentation culture of Coriolus versicolor LH1. Carbohydrate Polymers, 90(1), 174-180.

[4] Sudheesh, N., Ajith, T., Mathew, J., Nima, N., & Janardhanan, K. (2012). Ganoderma lucidum protects liver mitochondrial oxidative stress and improves the activity of electron transport chain in carbon tetrachloride intoxicated rats. Hepatology research: the official journal of the Japan Society of Hepatology, 42(2), 181-191.

[5] Jia, J., Zhang, X., Hu, Y., Wu, Y., Wang, Q., Li, N., et al. (2009). Evaluation of in vivo antioxidant activities of Ganoderma lucidum polysaccharides in STZ-diabetic rats. Food Chemistry, 115(1), 32-36.

[6] Handayani, D., Chen, J., Meyer, B. J., & Huang, X. F. (2011). Dietary shiitake mushroom (Lentinus edodes) prevents fat deposition and lowers triglyceride in rats fed a high-fat diet. Journal of Obesity, 2011, 1-8.