By Jay Udani, MD, and Mary L. Hardy, MD

Because the ayurvedic herb Gymnema sylvestre is becoming an increasingly popular ingredient in diabetes and weight-loss formulas, it is advisable that health care providers familiarize themselves with its uses and properties.

A venerable history supports the use of this herb for diabetes. Classical Ayurvedic texts recognize a condition similar to diabetes and identify a specific remedy, gymnema, referred to as the "sugar destroyer." This common woody climbing vine has been used for centuries in Indian traditional medicine to treat "honey urine," or what conventional Western medicine calls diabetes, a disease that has been diagnosed in Ayurveda for more than 2,000 years. In fact the concordance between the Ayurvedic diagnosis of madhu meha and the Western disease of diabetes is so close that Ayurveda recognizes both a congenital type of this disease and an acquired type, which correspond to our Type 1 and Type 2 diabetes.1

Gymnema or gurmar, to use its common Hindi name, means sugar destroyer, because it was noted that chewing the fresh leaves temporarily destroyed the taste of sugar in the mouth. Traditional uses for a decoction (water-based extraction process that involves boiling the plant material) of the leaves include the reduction of sugar in the urine, as a remedy for fever and cough, as a uterine tonic, cardiotonic, diuretic, or laxative, and to treat other urinary disorders.2-4 There have even been references for use of the root in the treatment of snakebite.4,5

However, since first studied by the British in India during the 19th century, modern herbal medicine has focused on the use of the gymnema leaf to decrease blood sugar. According to a recent review, gymnema is the herb most frequently studied in human clinical trials of diabetes, either as a single agent or in traditional Ayurvedic formulas.1 Additional information from phytochemical research and animal trials has elucidated a unique set of mechanisms for controlling blood sugar. These data plus a number of clinical trials, largely conducted in India, provide the supportive evidence for gymnema’s use as a hypoglycemic agent.

Constituents

A number of constituents have been isolated from this plant since the first chemical studies were reported at the end of the 19th century. The gymnemic acids, which were first isolated by Hooper in 1889, appear to be the most important constituents for lowering blood sugar.2 These exist in the plant in a complex mixture of at least nine closely related compounds, with the major component being identified as gymnemic acid A1.3,6,7

The "sugar destroying effect" of gymnema, on the other hand (affecting taste), is related to a polypeptide, gurmarin, which consists of 35 amino acids.3 The best-studied extract of gymnema, GS4, contains both the triterpene sapinoids (the gymnemic acids) as well as the polypeptide, gurmarin.

Pharmacokinetics/Mechanism of Action

Indian physicians are strong proponents of the efficacy of gymnema for diabetic patients, and the evidence suggests that this herb can lower blood sugar. Various preparations have been tested clinically including fresh leaves (chewed), dried leaf powder, water-based decoctions, a standardized extract (GS4), and multi-herbal formulas containing minerals and other herbs in addition to gymnema.1 Several pharmacologic actions of gymnema contribute to this herb’s hypoglycemic effects.

Although animals with normal blood sugar are largely unaffected,8-10 gymnema has been shown to cause increased insulin release from isolated islet cells as well as from animals with an intact pancreas.11,12 However, the pancreas is not essential for gymnema’s action as it can still normalize blood sugar in animals without any remaining beta-cell function.11 Actions of the herb have been identified that involve the liver and a variety of hepatic enzymes that regulate glucose production and storage, which favors glucose uptake from blood into cells.13 Some evidence exists for a reduction in absorption of glucose from the small intestine,14 and results of some animal trials have even suggested that gymnema may protect the pancreas from toxins and promote beta-cell regeneration.11,15 These last two actions have not been studied or observed in humans. An additional concern in people with diabetes is dyslipidemia. Gymnema also has been shown to increase fecal excretion of cholesterol but not bile acids in rats.16

The most unique action of gymnema involves its ability to decrease the perception of sweet taste. Traditionally, after chewing the fresh leaf, it was noted that the sense of sweetness was decreased for up to two hours. Bitter tastes also are obscured but not other taste sensations such as salty, pungent, acidic, or astringent.17 The constituents that are most responsible for this effect are the gymnemic acids and gurmarin. This effect is achieved by a direct action on the chordae tympani or sensory efferent nerves responsible for transmitting the sweet perception.18 This may be a clinically significant effect. Subjects who were previously exposed to a gymnema solution ate fewer total calories when offered ad libitum access to typical junk food. The effect was attributed to the change in sweet sensation and accompanying decrease in appetite caused by gymnema.19

Clinical Trials: Diabetes

Human clinical trials studying the effectiveness of gymnema on Type 1 and 2 diabetes mellitus are limited and most are flawed in their methodology. The number of eligible studies is further limited by the fact that many gymnema trials use proprietary multiple herb combinations. The following five studies described are single herb trials of gymnema.

A case series of eight Type 2 diabetic patients given 10 mg of dried Gymnema sylvestre leaf powder for 21 days found a statistically significant reduction in fasting blood glucose of 50.5 mg/dL and reduction in two-hour post-prandial blood glucose levels of 40.5 mg/dL at 21 days (P < 0.05) as compared with the same patients prior to treatment with gymnema.20 The study also found a non-significant increase in body weight of 0.9 kg in the subjects during this same 21-day period. There was no comparison group for this trial.

The same author published a controlled clinical trial in 1992 involving three research arms: Sixteen healthy volunteers received gymnema, and 43 Type 2 diabetic patients received either gymnema or tolbutamide (an oral hypoglycemic agent at a typical therapeutic dose) for a total of 21 days.21 The patients were not assigned to groups randomly and neither the patients nor the investigators were blinded. The non-diabetic patients experienced a significant reduction in fasting blood sugar (FBS, from 80.8 mg/dL to 71.6 mg/dL) at day 7. The diabetic patients in the gymnema treated arm experienced significant reductions in both FBS (152 mg/dL to 133 mg/dL) and post-prandial blood sugar (PPBS, 215 mg/dL to 142 mg/dL) at 21 days. The diabetic patients in the tolbutamide treatment arm also showed significant reductions in both FBS and PPBS at day 7, but not at day 14. Decreases also were reported in total cholesterol for both diabetic and non-diabetic patients (284 mg/dL to 244 mg/dL and 217 mg/dL to 200 mg/dL, respectively). P values were not provided for this short, non-randomized study.

A longer controlled clinical trial followed 47 Type 2 patients for 20 months.15 Each patient was already utilizing oral hypoglycemic agents and was stable on their medications with incomplete control. For half of the patients, their usual treatment continued. For the other half, 400 mg/d of GS4, a specific extract of gymnema, was added to their usual regimen. The average HBA1C in the GS4 group fell from 12% to 8.5%; FBS decreased as well from 174 mg/dL to 124 mg/dL; total cholesterol and triglycerides improved from 260 mg/dL to 231 mg/dL and from 170 mg/dL to 140 mg/dL, respectively. All results were significant at the P < 0.001 level. In the GS4 treatment group 23% of these patients were able to stop all hypoglycemic agents except for the gymnema. There are several cautions in interpreting this study. The patients were not allocated randomly to treatment groups and there were differences in fasting glucose at baseline. They were however fairly well matched for weight and body mass index (BMI).

In a small, short-term study, 10 healthy volunteers and six patients with Type 2 diabetes were given 2 g of an aqueous decoction of the shade-dried leaves of gymnema three times per day.22 Significant reductions in both FBS and PPBS were demonstrated. After 10 days, significant reductions were seen in the FBS of both normal (80.2 mg/dL to 69.2 mg/dL; P < 0.05) and Type 2 (135.7 mg/dL to 110.7 mg/dL, P < 0.02) patients. Significant reductions were also demonstrated in 30-minute PPBS (220 mg/dL to 180.7 mg/dL, P < 0.05) and two-hour PPBS (152.7 mg/dL to 121.1 mg/dL, P < 0.01) in the Type 2 group.

Only one study evaluated the effectiveness of gymnema in Type 1 diabetics (n = 63, 8-30 years old).23 Thirty-seven patients continued on their usual and customary care while 27 insulin-dependent patients added 400 mg/d of gymnema to their usual insulin regimen for eight months. The average insulin requirement in the supplemented group decreased from 60 uNPH/d to 45 uNPH/d. All gymnema patients experienced at least one episode of hypoglycemia that prompted decreases in their insulin dosages. Unfortunately, 40% of the patients dropped out before the end of the study due to persistent hypoglycemia in one patient and logistical difficulty with follow-up for the remainder.

As a group these trials are very suggestive of a positive effect for gymnema on blood sugar in both Type 1 and Type 2 diabetics. This coupled with the positive effect demonstrated on blood lipids is especially encouraging given the propensity for diabetic patients to have dyslipidemias. However, these trials have limitations in design and analysis typical of preliminary data. Well designed, larger clinical trials should be undertaken to confirm the effects seen in the trials from India.

Clinical Trials: Weight Loss

Gymnema was included as an ingredient in a weight-loss formula tested in 60 moderately obese subjects.24 The subjects were randomly allotted to one of three groups and received three times a day before meals either 4,667 mg of a highly bioavailable hydroxycitric acid (HCA-SX), the same amount of HCA-SX combined with 4 mg of niacin-bound chromium and 400 mg of a standardized gymnema extract (containing 25% gymnemic acid), or placebo. All subjects were instructed to eat a 2,000 cal/d diet and exercise regularly. The trial lasted eight weeks and outcomes measured included weight, BMI, and lipids. Both groups taking HCA-SX recorded a decrease in their BMI of 5-6% and the placebo group did not change. Total cholesterol, LDL, and triglycerides decreased for both HCA-SX groups. There was however no difference in response between the two HCA-SX groups, so the effects observed cannot be primarily attributed to the added gymnema. Blood sugar levels were not reported for this trial.

Adverse Reactions/Contraindications

To date, no adverse reactions or toxicities have been associated with the use of gymnema other than hypoglycemia. None of the clinical trials reviewed above reported any side effects. Gymnema may have a temporary blocking effect on the tongue for sweet taste if the leaves are chewed or a gymnema preparation is held in the mouth, but again, this is considered part of its therapeutic properties. Because of the likelihood that gymnema will decrease blood sugar, it should be used with caution in any person already using a hypoglycemic agent.