From the Townsend Letter for Doctors & Patients
Review & Commentary
Gymnema: A Key Herb in the Management of Diabetes
by Kerry Bone, FNIMH, FNHAA
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• Reduction of sweet cravings and appetite.
Dosage & Administration
For sweet-craving and sweet taste depression 1 to 2 mL per day of liquid extract is all that is necessary. This should be applied in divided doses directly to the tongue by dropper and rinsed off after one minute. This can be done at 2- to 3-hour intervals.
Contraindications & Cautions: None known.
Gymnema has been described in Hindu Materia Medica as a stomachic, diuretic and antiperiodic (e.g. to treat a periodic illness such as malaria). In Ayurvedic medicine indications for Gymnema include glycosuria, urinary disorders and diabetes mellitus.2 Gymnema has been used in the treatment of diabetes mellitus in India for over 2000 years.4
Dammarane-type saponins8 and a polypeptide consisting of 35 amino acid residues called gurmarin and other oleanane-type saponins (gymnemasins) have also been isolated.
Sweet Taste Suppression (Antisweet Activity)
In humans and chimpanzees, gymnemic acids suppress the sweet taste of all sweeteners but had no effect on taste receptors sensitive to bitter or salty substances in chimpanzees.15 The sweet suppressing activity of Gymnema extract in humans has been verified by measurement of gustatory evoked potentials.16 In experimental models the degree of suppression produced by gymnemic acid (measured by nerve response) varied from complete abolishment (aspartame, saccharin) to about 50% reduction (xylitol). Gymnemic acid had no effect on the responses to nonsweet (bitter, salty or sour) compounds. These results parallel psychophysical and electrophysical findings in humans.17
A gymnemic acid rinse used by human volunteers reduced the intensities of sucrose and aspartame to 14% of their pre-rinse levels.18 Over a recovery interval of 30 minutes these values increased linearly to 63% of the pre-rinse levels. A study involving human volunteers observed that a period of at least 30 seconds was required after tasting Gymnema infusion for the full sweet suppression effect to appear.19
Pretreatment with Gymnema extracts reduced the sweetness of sweeteners by an average of 77% in volunteers. There was no evidence for a differential effect across the range of sweeteners (3 concentrations each of acesulfame K, aspartame, sodium cyclamate, fructose, glucose, sucrose, stevioside and xylitol). The percentage reduction in sweetness was constant across the low, medium and high concentrations. Such results suggest that a receptor occupancy or blocking mechanism is unlikely. A type of 'mixed' inhibition involving an effect on the breakdown of the stimulus/receptor complex is more likely.20
For further antisweet activity demonstrated in humans see below in Clinical Studies (Weight Loss).21
Gymnema extract and some isolated constituents have inhibited glucose uptake in isolated small intestinal tissue.26,27 Gymnema extract and gymnemic acids inhibited the intestinal absorption of glucose in humans and rats.28,29 In evidence of this, two fractions obtained from Gymnema (containing gymnemic acids) suppressed potassium-induced contraction of isolated ileal longitudinal muscle, interfered with the increase in transmural potential difference induced by glucose and inhibited the elevation of blood glucose in vivo (route unknown).30 Two gymnemic acids suppressed the contraction of smooth intestinal muscle, most likely by inhibiting glucose uptake.28
Oral administration of Gymnema extract reduced post-prandial serum glucose and improved glucose tolerance in mildly diabetic rats. Pancreas weight and content of insulin were not changed.31 Gymnema corrected hyperglycaemia in mild alloxan-diabetic rats and significantly prolonged lifespan in severe alloxan-diabetic rats (i.e. with completely destroyed pancreatic tissue). The authors suggested that the prolonged survival time was due to the adaptogenic activity of Gymnema.32
Feeding with Gymnema leaf powder regulated blood sugar levels in alloxan-diabetic rabbits and increased the activities of enzymes which facilitate the use of glucose by insulin-dependent pathways (phosphorylase, gluconeogenic enzymes and sorbitol dehydrogenase). Uptake of glucose into glycogen was increased in liver, kidney and muscle. Gymnema treatment also increased the incorporation of glucose into the protein components of these tissues.22 The hypoglycaemic activity of Gymnema occurs in a slow and steady manner: in rabbits with mild alloxan-diabetes between 12 and 24 weeks of treatment was required.4
Blood sugar levels in normal and diabetic rats were lowered 2 hours after oral administration of a Gymnema concentrate (50-400 mg/kg, 19.5:1), but Gymnema was 6 times less potent than oral tolbutamide in the diabetic animals.33 Two Gymnema extracts returned fasting blood glucose levels to normal after 20 to 60 days of oral administration to diabetic rats. A rise in serum insulin towards normal fasting levels occurred and the number of beta cells within pancreatic tissue increased.23 This suggests a restorative effect on pancreatic tissue.
The crude saponin fraction of Gymnema and gymnemic acid IV reduced blood glucose levels in streptozotocin-diabetic mice when administered by injection. Gymnemic acid IV also increased plasma insulin levels.34 Gymnemoside b and gymnemic acids III, V and VII (route unknown) produced some inhibitory activity on glucose absorption after oral glucose loading in rats, but gymnemic acid I and gymnemasaponin V were inactive.35
Appetite & Weight Loss
Two fractions of Gymnema extract (containing 160-360 mg/g of gymnemagenin) decreased body weight gain and food intake dose-dependently when given orally (0.05-1.0 g/kg) to rats for 22 days. Administration of a Gymnema fraction (1.0 g/kg) containing 363 mg/g of gymnemagenin increased faecal excretion of cholesterol, total neutral steroids, total bile acids and cholic acid-derived bile acid. These increases correlated with faecal gymnemagenin levels.37
A controlled study on insulin-dependent diabetics found that a water-soluble Gymnema extract (400 mg/day corresponding to about 8 g of starting dried herb) reduced insulin requirements (by about 50%). Over the duration of treatment Gymnema lowered fasting mean blood glucose (by about 35%), glycosylated haemoglobin and glycosylated plasma protein levels from baseline values. Cholesterol was significantly reduced and brought to near normal levels. Triglycerides, free fatty acids and serum amylase were also lowered. The treatment period ranged from 6-30 months. The significant decrease in glycosylated haemoglobin occurred after 6-8 months of Gymnema treatment but remained significantly higher than normal values. None of these reductions were observed in control patients on insulin therapy alone who were studied over a period of 10-12 months. The authors suggested that Gymnema enhanced endogenous insulin production, possibly by pancreatic regeneration, as levels of C-peptide, a by-product of the conversion of proinsulin to insulin, were apparently raised (in comparison to both the insulin alone group and normal subjects).24
A second study by the same research group found that the same Gymnema preparation (400†mg/day) produced similar results for non-insulin-dependent diabetics. Fasting blood glucose, glycosylated haemoglobin and glycosylated plasma protein were significantly reduced compared to baseline values (p<0.001) after 18-20 months of treatment. None of these reductions were observed in patients receiving conventional therapy alone who were studied over a period of 10-12 months. By the end of the treatment period cholesterol, triglycerides, phospholipids and free fatty acid levels were also significantly reduced compared to baseline values in those receiving Gymnema (p<0.001). Control patients receiving only conventional therapy achieved reductions in cholesterol, triglycerides and free fatty acids (p<0.05-p<0.001). Fasting and post-prandial serum insulin levels were significantly increased in the Gymnema group compared to those taking only conventional drugs (p<0.01). Twenty-one of the 22 patients were able to reduce their intake of hypoglycaemic drugs; 5 of these discontinued hypoglycaemic drugs entirely and maintained their blood glucose homoeostasis with Gymnema extract alone. The authors' suggestion of beta cell regeneration or repair facilitated by Gymnema was supported by the higher insulin levels in the serum of patients after Gymnema supplementation. Gymnema administration to healthy volunteers did not produce any acute reduction in fasting blood glucose level.25
A clinical trial recently conducted in the US provides further support for the use of Gymnema in the management of diabetes. Of 65 patients tested over the 90-day trial, Gymnema tablets reduced mean fasting glucose levels by 11%. Average post-meal glucose levels showed a decline of 13% and glycosylated haemoglobin levels dropped 6.8%. In a subset of patients with the poorest control, results were more substantial. Pre-meal readings averaged an 18% decline, with post-meal levels reduced by 28%. Corresponding glycosylated haemoglobin levels declined 10%. Improved glucose control with Gymnema enabled 16% of the participants to decrease their prescription medication usage.43 The tablets used in the trial contained 400 mg of Gymnema extract (equivalent to around 4 g of leaf) standardised to 25% gymnemic acids. The dose used was two tablets per day.
Thirty minutes after the last set of ratings a test meal consisting of snacks was presented in the context of providing refreshment. Participants were told that this was not part of the experiment. The Gymnema group ate less total calories (501 ± 237 vs. 638 ± 333, p<0.006), total carbohydrates (p<0.003), total protein (p<0.018) and total fat (p<0.015) than participants whose taste perception was normal (tea group).
The substantial assistance of Michelle Morgan in preparing this monograph is gratefully acknowledged.
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43. Joffe DJ, Freed SH. Newsletter for Professionals in Diabetes Care. Oct 31, 2001, Issue 76.
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