Gymnema (Gymnema sylvestre)
Background
Gymnema sylvestre is a member of the Asclepiadaceae family. It has been used in Ayurvedic medicine to treat madhu meha or “honey urine.” Gymnema came to be known as gurmar or the “destroyer of sugar” because Ayurvedic physicians observed that chewing a few leaves suppressed the taste of sugar. It has been used in India for the treatment of diabetes for over 2,000 years.
The medicinally active parts of the plant are the leaves and the roots. Plant constituents include two resins (one soluble in alcohol), gymnemic acids, saponins, stigmasterol, quercitol, and the amino acid derivatives betaine, choline, and trimethylamine.
Pharmacology
The important active ingredient in Gymnema sylvestre is an organic acid called gymnemic acid. This is a triterpene glycoside that suppresses sweetness in humans. From this glycosidic fraction, six triterpene glycosides — gymnemosides a, b, c, d, e, and f — were isolated. There are four triterpenoid saponins and six known gymnemic acids found in G. sylvestre. However, the principal constituents are gymnemic acid and gymnemasaponin. Gurmarin is a polypeptide isolated from the leaves that consists of 35 amino acid residues, including three intramolecular disulfide bonds. It has a molecular weight of 4000 and is inhibitory to neural responses to sweet taste stimuli.
Mechanism of Action
Gymnema sylvestre is a stomachic, diuretic, refrigerant, astringent, and tonic. Its antidiabetic activity is due to a combination of mechanisms. Recent pharmacological studies have shown that gymnema acts on both the taste buds in the oral mucosa and the absorptive surface to the intestines. The structure of the taste buds that detect sugar in the mouth is similar to the structure of the tissue that absorbs sugar in the intestines. The active ingredient, gymnemic acid, acts on both these sites.
Gymnemic acid is made up of molecules whose atom arrangement is similar to that of glucose molecules. Those molecules fill the receptor locations on the taste buds for a period of 1 to 2 hours, thereby preventing the taste buds from being activated by any sugar molecule present in food. Similarly, the glucose-like molecules in the gymnemic acid fill the receptor locations in the absorptive external layers of the intestine, thereby preventing the intestine from absorbing the sugar molecules. Therefore, gymnemic acids from the leaves suppress the elevation of blood glucose level by inhibiting glucose uptake in the intestines. The leaves also contain chlorophyll, xanthophylls, carotene, phytol, and lime salts. Gymnema sylvestre has also been found to reduce the bitter taste of certain foods.
Gymnema increases the activity of enzymes responsible for glucose uptake and utilization, and inhibits peripheral utilization of glucose by somatotrophin and corticotrophin. Extracts of this plant have also been found to inhibit epinephrine-induced hyperglycemia. Gymnema has even been shown to regenerate insulin-producing beta cells of the pancreas, leading to an enhancement in the production of endogenous insulin, further controlling blood sugar. Gymnema inhibits adrenocortical activity and prevents the normal hyperglycemic response of the anterior pituitary gland, which acts in turn by inhibiting peripheral glucose metabolism induced by somatotropin and corticotropin hormones. The extracts from gymnema leaves have been shown to suppress the intestinal smooth muscle contraction, decrease oxygen consumption, inhibit the glucose evoked-transmural potential, and prevent increased blood glucose levels. Studies indicate gymnema inhibits the increase in the blood glucose level by interfering with the intestinal glucose absorption process.
Gymnema is antiviral. It increases oxygen uptake, blood pressure, and secretions of liver and pancreas. The leaves have been found to stimulate the heart, uterus, and circulatory system. It raises urine output. As an agent to promote weight loss, gymnema may help control appetite and carbohydrate cravings.
Gymnema increases the blood’s capacity to take up oxygen, resulting in higher physical and mental performance and increased energy levels. This is beneficial for keeping in shape and staying active. The leaves are used for stomach ailments, constipation, water retention, and liver disease. The leaves are also noted for lowering serum cholesterol and triglycerides.
Clinical Studies
Recent clinical trials have shown that Gymnema sylvestre is useful for treating both insulin-dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM).
Blood Sugar and Insulin Control
The first scientific confirmation of gymnema’s use in diabetes came almost 70 years ago when it was demonstrated that the leaves reduced urine glucose in diabetics. Four years later, it was shown that gymnema had a blood glucose lowering effect when there was residual pancreatic function, but was without effect in animals lacking pancreatic function, suggesting a direct effect on the pancreas.
Another study showed that in diabetic rats, fasting blood glucose levels returned to normal after 60 days of gymnema with oral administration. The therapy led to a rise in serum insulin to levels closer to normal fasting levels. In diabetic rat pancreas, gymnema was able to double the islet number and beta cell number.
In 1981, it was demonstrated that oral administration of the dried leaves of gymnema brings down blood glucose and raises serum insulin levels. In 1988, a study showed a normalization of glycosylated hemoglobin and plasma proteins (indicators of long term glucose control) from gymnema administration. In 1990, it was shown that administration of gymnema extract to diabetic animals was accompanied by a regeneration of beta cells in the pancreas. This brought about glucose homeostasis through increased serum insulin levels provided by repair/regeneration of the pancreas.
A study was conducted on both Type I and II diabetics given a standardized gymnema extract, from the leaves, for a period of 2 years. Twenty-seven patients with IDDM who were on insulin therapy were administered 400 mg/day of gymnema for 6 to 30 months. Insulin requirements were decreased by about one-half and the average blood glucose decreased from 232 mg/dL to 152 mg/dL. Glycosylated plasma protein levels also decreased. Gymnema appeared to enhance endogenous insulin by regeneration of the residual beta cells in IDDM. Serum lipids also returned to normal levels with gymnema therapy, which may help prevent cardiovascular disease. Most impressively, an increase in C-peptide levels were found, which is a strong indication of restoration of insulin production.
Dr Baskaran and Dr Ahamath, at the Department of Biochemistry, Post-Graduate Institute of Basic Medical Sciences in Madras, India, investigated the therapeutic properties of an extract from the leaves of Gymnema sylvestre in controlling hyperglycemia in 22 Type II diabetic patients on conventional oral anti-hyperglycemic agents. Gymnema sylvestre (400 mg/day) was administered for 18 to 20 months as a supplement to the conventional oral drugs. During supplementation, the patients showed a significant reduction in blood glucose, glycosylated hemoglobin, and glycosylated plasma proteins. Conventional drug dosage could be decreased. Five of the 22 diabetic patients were able to discontinue their conventional drug and maintain their blood glucose homeostasis with Gymnema sylvestre alone. These data suggest that the beta cells may be regenerated/repaired in Type II diabetic patients on Gymnema sylvestre supplementation. This is supported by the appearance of raised insulin levels in the serum of patients after gymnema supplementation. Additionally, gymnema significantly improved cholesterol, triglyceride, and free fatty acid levels that were elevated.
Adaptogenic Effect
Some authors are speaking of the “adaptogenic” nature of gymnema, since it increases the body’s ability to adapt to the presence of sugar. The increase in longevity noted above was ascribed to “cardiotonic and adaptogenic characteristics produced by increasing resistance and immunity in diabetic animals.” To be a true adaptogen, it would need to “normalize” function, not just prolong life. Recently, researchers have reported gymnema prevents death due to hypoglycemia in rats injected with beryllium nitrate. That gymnema prevents both rises and falls in blood sugar and causes no significant change in normal blood sugar levels appears to be in full harmony with the concept of an adaptogen.
In other animal studies, gymnema has been found to double the number of insulin-secreting beta cells in the pancreas and return blood sugar to almost normal. Most cases have shown it to lower blood sugar to normal levels and not to a point below normal, as seen with many other antidiabetic drugs. However, studies conducted in India as early as 1930 showed that the leaves could cause hypoglycemia in experimental animals.
The anti-sweet peptide, gurmarin, purified from the leaves of Gymnema sylvestre, is highly specific to sweet taste so that responses to various sweeteners are all suppressed. Gurmarin acts on the apical side of the taste cell, possibly by binding to the sweet taste receptor protein.
In a very thorough animal study, gymnema greatly reduced the blood glucose levels in alloxan-induced diabetic rabbits. It was thought gymnema effects were mediated through stimulation of insulin release resembling what was observed with sulfonylureas, or through inhibition of intestinal absorption of glucose as observed with the biguanides, or through stimulation of one of the insulinogenic signals promoting insulin release.
Gymnema reversed the glycogen and protein depletions and lipid accumulation in the diabetic animals. The theory that gymnema works by increasing the levels of circulating insulin was supported by observations of altered enzyme activities in the liver, kidney, and muscles. Most of the insulin-dependent enzymes (hexokinase, glycogen synthetase, glyceraldehyde-3-phosphate dehydrogrenase, and glucose-6-phosphate dehydrogenase) were significantly more active in the gymnema-treated animals than in control diabetic animals. It also increased the activity of enzymes affecting the utilization of glucose by insulin-dependent pathways: phosphorylase, gluconeogenic enzymes, and sorbitol dehydrogenase. Pathological changes in liver and kidney were reversed by the treatment. The study reports in great detail findings supporting the notion that gymnema corrects the metabolic derangements in diabetic rabbit liver, kidney, and muscle tissues.
Other studies have found similar normalizing effects of various enzymes and chemicals of the kidney, heart, liver and brain, including hexuronic acid, hexoses, hexosamines, non-amino polysaccharides, hyaluronic acid, heparin sulfate, chondroitin sulfates, and sialic acid.
In another study utilizing alloxan diabetic rabbits and one human patient, gymnema brought down the fasting blood glucose levels, together with serum cholesterol and triglyceride levels, while improving serum protein levels. The hypoglycemic action took several weeks to develop. Oral administration in normal rats apparently has no significant effect, but only in rats made hyperglycemic experimentally (alloxan, anterior pituitary-treated, tolbutamide, adrenaline).
While gymnema does not lower blood sugar levels in normal subjects, it does appear to prevent a rise in blood sugar levels in normal subjects. This result has been attributed to a pancreotropic effect due to sensitization of beta cells of islets of Langerhans for secreting larger amounts of insulin in response to glucose. In addition, it markedly inhibited somatotropin- and corticotropin-induced elevations in blood sugar levels.
An interesting finding in clinical tests showed that healthy people with normal insulin levels showed no lowering of blood sugar levels or hypoglycemic effects after taking the herb.
Dosage
Gymnema sylvestre in tea form offers the best results. It has been determined that a daily dose of 200 mg is optimal in order to utilize its effectiveness in the area of weight management. The typical therapeutic dose (for treatment of hyperglycemia), standardized to contain 24% gymnemic acids, is 400 to 600 mg daily. In adult-onset diabetics, ongoing use for periods as long as 18 to 24 months has proven successful. In reducing the symptoms of glycosuria, the dried leaves are used in daily doses of 3 to 4 grams for 3 to 4 months. Because it acts gradually, gymnema extract should be consumed regularly with meals for several days or weeks and can be taken for months or years with no significant side effects.
Drug Interactions
Patients taking gymnema may require dosage adjustments of other antidiabetic drugs. However, in some cases, it may make the treatment more effective. Some patients do develop hypoglycemia when taking gymnema along with other medications. This is because improved insulin production and release during gymnema therapy may decrease the need for other medication and thus lower blood glucose levels, unless the dosage of conventional oral medication or insulin is lowered.
Some of the effects of gymnema may be enhanced by MAOI antidepressant medications, fenfluramine, salicylates, and tetracyclines. Its actions may even be decreased by concomitant use of oral contraceptives, epinephrine, phenothiazines, marijuana, and thyroid hormones. Gymnema has diuretic action that increases the renal excretion of sodium and chloride, and may potentiate the hyperglycemic and hyperuremic effects of glucose elevating agents. Patients using diuretics may require dosage adjustments of antidiabetic drugs.
Certain botanical medications, including antidepressants (St. John’s wort) and salicylates (white willow and aspirin), can enhance the blood sugar-lowering effects of Gymnema sylvestre, whereas certain stimulants, such as ephedra (Ma Huang), may reduce its effectiveness. The antidiabetic ability of this herb may be decreased by concomitant use of acetazolamide, oral contraceptives, corticosteroids, dextrothyroxine, epinephrine, ethanol, glucagon, guanethidine, and marijuana. The antidiabetic effects may also be decreased when used in conjunction with phenothiazines, rifampin, thiazide diuretics, and thyroid hormones.
The antidiabetic action of gymnema may be enhanced when it is used with allopurinol, anabolic steroids, chloramphenicol, clofibrate, fenfluramine, guanethidine, MAOI, phenylbutazone, probenecid, and phenyramidol. This action of gymnema may also be enhanced when used in conjunction with salicylates, sulfinpyrazone, sulfonamides, and tetracyclines. The ability of gymnema to increase insulin production and secretion may be antagonized by heparin.
Adverse Reactions
At typical recommended doses, dietary supplements containing gymnema are not associated with significant adverse side effects. Mild gastrointestinal upset may occur if gymnema is taken on an empty stomach; therefore, consumption with meals is recommended. Caution is urged, however, with extremely high doses, which may have the potential to induce hypoglycemia in susceptible individuals. It can also alter the bitter and sweet taste sensation.
