Diabetes, as a metabolic disorder caused by a lack of insulin and characterized by hyperglycemia, is nowadays no longer considered a rare, congenital disease, becoming increasingly common and thus a serious problem.
In this article, we will go through Mushrooms of the Genus Ganoderma Used to Treat Diabetes and Insulin Resistance by Wińska, K. et al. in 2019 , a review on perspectives, recent advances, and major challenges of Ganoderma species in the field of diabetes, our focus being on the effects that bioactive compounds found in Ganoderma species have, the review also including a diabetic mice model.
Running short on time? You may prefer to read LingZhi & Diabetes (Summary) that covers the information in this study in clear and concise point form.
This article will cover:
diabetes and the state of treatment at the time of the study's publication;
the experimental data and results of administering Ganoderma extracts to diabetic mice;
the key bioactive compounds of Ganoderma species and their interactions; and
how you might apply the information presented in this review.
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Diabetes & The State Of Its Treatment
This review begins with quoting data published by the International Diabetes Federation in the eighth edition of the Global Diabetes Map. illustrating the rapid deterioration of our populations into a diabetic state:
"...in 2017 the number of adults of diabetes worldwide patients (20–79 years) reached 415 million. It should be noted that in 2000 there were “only” 151 million such patients. Estimates suggest that by 2045 the number of diabetic patients could reach 629 million."
Causes & Types Of Diabetes
Diabetes occurs when blood glucose (blood sugar) remains chronically elevated and results in glucose toxicity in the body. This is usually due to impairment or insufficiency of islet β-cells (beta-cells) in the pancreas that diminishes insulin biosynthesis and gradually deteriorates whole body functions.
Type 1 diabetes primarily involves islet β-cells that have declined in insulin production and high blood glucose arises as a result of lacking sufficient insulin. Autoimmunity of the pancreatic islet β-cells, demonstrated by the presence of corresponding antibodies, is the cause of type 1 diabetes
In type 2 diabetes, insulin resistance also contributes in perpetuating the disorder. This involves cells of the liver and muscles failing to effectively remove glucose from circulating blood and store it as glycogen due to their poor sensitivity to insulin.
Type 1 Diabetes
Type 2 Diabetes
Autoimmunity in which the body attacks pancreatic islet β-cells inhibiting insulin production
Insulin resistance in which the pancreas produces insulin but the body has poor response to insulin
Presence of antibodies that target islet β-cell antigens
Absence of antibodies that target islet β-cell antigens
Current Treatment Of Diabetes & Their Disadvantages
Current treatment involves the use of drugs that influence certain pathways relating to diabetes. These include drugs such as metformin, which help improve insulin sensitivity, to others such as acarbose and miglitol, which inhibit the breakdown of complex sugars into glucose in the small intestine.
However, the use of synthetic drugs is known to come with their drawbacks. Metformin, for example, while safe, inexpensive and effective in treating type 2 diabetes, risks inducing lactic acidosis with prolonged use.
Furthermore, when use of metformin is contraindicated, thiazolidinediones (TZD) such as pioglitazone and rosiglitazone are used which, unfortunately, have many side effects such as weight gain and heart failure thought to be caused by increased fluid retention seen in patients treated with TZD.
Overall, the authors also listed multiple other examples of medication for diabetes as well as their reported side effects.
This has led researchers to seek natural alternatives.
One of many alternatives researchers have turned to is the Ganoderma genus of fungi. Tropical, woody, and inedible, the species comprising this group of fungi numbers about 300 and have been used in various traditional medicinal practices, most prominently in traditional Chinese medicine for chronic diseases such as nephritis, hypertension, arthritis, insomnia, and asthma.
From analyzing results published regarding the use of substances and extracts from genus Ganoderma for anti-diabetic purposes, the authors concluded that two groups of bioactive compounds were most important: polysaccharides and terpenoids, and therefore went on to discuss their anti-diabetic activity for the remainder of their review.
Blood Glucose Reduction Effects of Ganoderma Extracts
As mushrooms of the genus Ganoderma contain both water- (mainly polyssacharides) and alchohol-soluble (mainly triterpenoids) substances, the authors reviewed past research on both water and alcohol extracts of G. lucidum for their ability to reduce blood glucose in rodents with induced diabetes, the results of which are encouraging.
The authors first quote Seto et al.'s research in 2009 with a water extract prepared with the powder of capsules containing 95% G. lucidum. Blood glucose levels were reduced by more than half in normal mice (168.5 mg/dL to 68.5 mg/dL) and obese diabetic mice (668.5 mg/dL to 288.4 mg/dL) after 4 weeks at a dose of 0.3 g/kg body weight of said extract.
Seto et al. have thus successfully demonstrated that Ganoderma extracts, at least in mice, helps to lower blood glucose levels through prolonged use at reasonable dosage (0.3 g/kg is 21 g of extract for a person weighing 70 kg).
This is mirrored closely by yet other researchers who used various extracts prepared with fruiting bodies (the mushroom itself) and water or organic solvents (ethanol, methanol, and petroleum ether).
It is worth noting here that herbal extractions performed on identical batches of fruiting bodies but with different solvents (various organic solvents and water) yield extracts of different nutritional profiles.
The evidence presented suggests that Ganoderma species carry a wide range of bioactive compounds that suppress blood glucose levels, the prime hallmark of diabetes and immediate cause of glucose toxicity.
Polysaccharides Isolated from Ganoderma Species & Their Interactions
Polysaccharides are long chains of at least ten monosaccharides which are in turn single molecules of somple sugars such as glucose, fructose, and so on.
Ranging from being long linear chains to being highly branched, polysaccharides of Ganoderma species are used as both sources of energy and building blocks for growth and repair. Amongst the various polysaccharides, the beta-glucan polysaccharides are of greatest interest to researchers for their medicinal properties and use in many diseases.
When isolating polysaccharides for study, apart from naming and describing their chemical formulae, the shape and structure of each type of polysaccharide is of particular importance as their biological effects depend on their size, degree of branching, water solubility, number of side branches, and length of side chains.
The authors summarised in their Table 2 the enzymes directly or indirectly related to diabetes and whose activities are affected by Ganoderma polysaccharides as demonstrated by other researchers. Particularly noteworthy are the demonstrations of interactions with enzymes of the pancreatic islet, liver, and skeletal muscle which all take part in the body's glucose metabolism.
The following is a summary of the main anti-diabetic interactions between G. lucidum polysaccharides and various biological functions as demonstrated by other researchers and reviewed by the authors:
Reduction in blood glucose levels observed after administering extract, the extract facilitating the transport of calcium ions into pancreatic β cells, raising circulating insulin levels as early as 1 hour after administration;
Significant decrease in fasting blood glucose concentration, excess insulin, and epididymal (a testicular duct) white fatty tissue;
Reduction in levels of enzymes involved in gluconeogenesis (sugar production by the liver);
Protects against alloxan-induced pancreatic islet damage due to free radical capture;
Resensitizing of cells to insulin and reducing insulin resistance;
Low molecular weight polysaccharides regulate the metabolism of anti-apoptosis proteins and related mRNA expression, protecting the body’s pancreas cells against apoptosis and also initiating their regeneration;
Improves wound healing, a major concern in diabetics, by accelerating formation of scar tissue and new blood vessels (angiogenesis);
Oral use of inulin with Ganoderma polysaccharides may have synergistic effects which increase insulin sensitivity.
Following the section on G. lucidum, the authors also reviewed the research on Ganoderma atrum polysaccharides, their effects of pancreatic islet β-cell preservation, insulin resensitisation, and so on being of the same ilk as that of G. lucidum's polysaccharides.
Terpenoids Isolated from Ganoderma Species & Their Interactions
Well-known in research and on the market, terpenes are hydrocarbons consisting of isoprene units in various arrangements. When containing various functional groups, they are known as terpenoids.
Hence, the prefix 'tri-' in triterpenoids indicates that they contain six isoprene units while '-terpenoid' indicates the presence of other functional groups in addition to the main terpene skeleton.
Over 140 triterpenoids have previously been identified and studied in species of the genus Ganoderma, of which as many as 15 of them are derived from G. lucidum.
Triterpenoids exhibit their anti-diabetic effects by inhibiting enzymes that are associated with glucose, cholesterol, and other diabetic hallmarks.
Being structurally reminiscent of steroid hormones, it is speculated that triterpenoids bind with glucocorticoid-responsive elements (GRE), suppressing pro-inflammatory proteins and increasing the expression of anti-inflammatory proteins.
Also, despite being inclined to binding to cell membranes which is said to limit their bioavailability, it has been experimentally found that triterpenoids penetrate both cell membranes and the blood–brain barrier, accumulating in the liver, circulatory system, and other tissues and exerting their beneficial effects.
As with the section reviewing polysaccharides, the authors summarised in their Table 3 the enzymes directly or indirectly related to diabetes and whose activities are affected by Ganoderma terpenoids as demonstrated by other researchers.
The following is a summary of the main anti-diabetic interactions between G. lucidum terpenoids and various biological functions as demonstrated by other researchers and reviewed by the authors:
Inhibits aldose reductase, an enzyme that converts glucose to sorbitol - sorbitol accumulation leading to complications such as neuropathy, nephropathy, cataracts, and retinopathy;;
Inhibits α-glucosidase present in the gut, an enzyme that converts complex sugars into glucose, thus inhibiting glucose uptake into the bloodstream;
Inhibits HMG-CoA reductase enzyme which in turn inhibits LDL cholesterol formation.
Summarized Treatment Mechanisms by Ganoderma
In viewing diabetes mellitus as a disease involving disorder across multiple metabolic pathways, the authors conclude their review by restating the key effects and mechanisms of various bioactive compounds found within Ganoderma species regarding diabetes.
On pancreatic islet β-cells:
Due to impairment or insufficiency of β-cells by autoimmunity or high glucose levels (hyperglycemia), insulin production diminishes, leading to chronic toxicity from high blood glucose levels that gradually deteriorates organ tissues and thus whole body functions;
Ganoderma polysaccharides can inhibit β-cell apoptosis and initiate their regeneration;
Ganoderma peptidoglycans (cell wall fragments, also polysaccharides) raise insulin release by β-cells, improving insulin resistance.
On the liver and digestive system:
Ganoderma polysaccharides increase glycogenesis, the process by which the liver removes glucose from circulation and stores it as glycogen within liver cells.
By inhibiting α-glucosidase in the small intestine, Ganoderma triterpenoids inhibit the conversion of complex sugars into glucose in the gut, thereby reducing the uptake of glucose into circulating blood.
On various bodily functions:
Especially in type 2 diabetes, decreasing insulin secretion commonly coincides with increasing insulin resistance;
Hyperglycemia and glucotoxicity produces excess reactive oxygen species (ROS), compromising the body's antioxidant defence system - Ganoderma polysaccharides modulate the various enzymes involved in antioxidant defence, mitigating the effects of ROS;
By controlling the various factors leading to diabetes, Ganoderma bioactive compounds help to reduce fasting blood glucose levels in a holistic manner;
As a final note, the authors emphasised the satisfactory effect and medical potential of Ganoderma, citing 61 other clinical studies carried out for various indications, not only diabetes.
Adding LingZhi Into Your Schedule For Diabetes
When it comes to chronic illnesses, it is important to remember that thy do not commence on the day of diagnosis as if they did not exist the day before. Rather, they are usually the result of poor lifestyle choices made over many years.
It is therefore just as important to not only make the necessary changes to your daily routine, but to also ensure you can sustain them day after day for them to effect improvement in the long term, keeping in mind that any information given by your doctor or obtained through your own reading should be unpacked and understood and the required changes to your lifestyle formulated before acting upon it.
Whatever your lifestyle changes, here are a few suggestions based on what we have discussed thus far if you are or will be using Ganoderma mushrooms:
Ingest Ganoderma polysaccharides at mealtime to reduce the uptake of glucose into circulating blood by your small intestine;
Ingest Ganoderma polysaccharides and triterpenoids daily for 4 - 8 weeks or longer (emulating mice study);
starting with a lower dose as recommended by your doctor or nutritionist, you may choose to work up to 0.3 grams of Ganoderma extract per kilogram of body weight or a reasonable equivalent under supervision (again, emulating mice study).
Teas are easy to prepare and are a good source of Ganoderma polysaccharides and triterpenoids.
 Wińska, K., Mączka, W., Gabryelska, K., & Grabarczyk, M. (2019); Mushrooms of the Genus Ganoderma Used to Treat Diabetes and Insulin Resistance; Molecules (Basel, Switzerland), 24(22), 4075. https://doi.org/10.3390/molecules24224075
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