Gymnema
Gymnema sylvestre R.Br. 1 Family: Asclepiadaceae
Meshashringi , gurmar , merasingi , periploca of the woods
 
Clinical Overview
Uses
The plant has been used in traditional medicine, most notably to control blood glucose. Use as a lipid-lowering agent, for weight loss, and inhibition of caries also has been investigated. However, little to no clinical information is available to support the use of gymnema for any indication.

Dosing
Typically, clinical studies investigating antidiabetic effects have used 200 or 400 mg of an extract standardized to contain 25% gymnemic acids administered twice daily.

Contraindications
Use with caution in patients who have a history of hypoglycemic reactions.

Pregnancy/Lactation
No information on use in pregnancy or lactation was found. Manufacturers of commercial supplements recommend against use during pregnancy.

Interactions
None well documented.

Adverse Reactions
Hypoglycemia may occur.

Toxicology
There are no published reports of human toxicity with the plant.

 
Botany
Gymnema sylvestre is a woody, climbing plant indigenous to the tropical forests of central and southern India. Distribution is worldwide and it is recognized in the traditional medicinal literature of many countries including Australia, Japan, and Vietnam. The leaves are most commonly used, but the stem also appears to have some pharmacologic action. Gymnema has been referred to in some texts as Asclepias geminata Roxb., Gymnema melicida Edg., and Periploca sylvestris Willd.
 
History
Gymnema has played an important role in Ayurvedic medicine for centuries. Its use has been confined primarily to the management of diabetes mellitus and similar hypo/hyperglycemic conditions. As early as 1930, the pharmacologic effect of the plant was investigated. 2 The leaves also have been used for stomach ailments, constipation, water retention, and liver disease. The flowers, leaves, and fruits have been used in the treatment of either high or low blood pressure, tachycardia, and arrhythmias. 3 Chewing the leaves destroys the ability to discriminate the sweet taste, giving it the common Hindi name of gurmar , or “sugar destroyer.” 4
The plant has been used alone and as a component of the Ayurvedic medicinal compound Tribang shila , a mixture of tin, lead, zinc, G. sylvestre leaves, neem ( Melia azadirachta ) leaves, Enicostemma littorale , and jambul ( Eugenia jambolana ) seeds. The plant has become available in a number of commercial otc herbal products in North America and Europe.
 
Chemistry
Gymnemic acids, a group of triterpenoid saponins, are the main class of chemical constituents isolated from G. sylvestre . The quantity of gymnemic acids extracted from the leaves varies according to the location of cultivation and the time of harvesting; concentrations varying between 0.67% and 1.06% have been reported. Multiple gymnemic acid congeners have been identified. Gymnemic acids Ι-VΙ were isolated and characterized from aqueous leaf extracts and gymnemic acids XV-XVΙΙΙ from the saponin fraction of the leaves. Gymnemic acids VΙΙΙ-XΙΙ have been elucidated as glucosideuronic acid derivatives of gymnemagenin. 5 Gymnemic acids are thought to be responsible for the antidiabetic activity of G. sylvestre ; gymnemic acid VΙΙΙ was the major component of an extract shown to stimulate insulin release from the pancreas. 6 Also present in gymnema extracts are gymnemasaponins Ι-V, a group of antisweet principles with a novel D-glucoside structure. The structure of gurmarin, another antisweet agent found in gymnema, has been elucidated as a polypeptide comprising 35 amino acid residues. 7 Gymnemosides A-F have been isolated from alcoholic extracts of the leaves of G. sylvestre ; the structure of gymnemosides A and B have been elucidated. 8 Other constituents include gymnemanol, gymnemasins, gymnemasides, gypenoside, and conduritol, 6 an agent with antidiabetic properties.
 
Uses and Pharmacology
Diabetes   In vivo studies have indicated that extracts of G. sylvestre containing gymnemic acid suppress the elevation of blood glucose levels by inhibiting glucose uptake in the intestine 9 and by increasing insulin release from the pancreas. 6 The major mode of action was proposed to be through increased permeability of the β-cell plasma membranes, leading to unregulated loss of insulin from the cells. The high saponin glycoside content of the extract is thought to be responsible for this action. In addition, a calcium2+ -sensitive component is present; some degree of insulin release may occur through channel-independent calcium2+ influx into the β-cells, perhaps through the pores formed by plasma membrane disruption. 6
Animal data   A number of studies have evaluated the effects of G. sylvestre on blood sugar in animals. 10 In one typical study, diabetic rats received an alcoholic extract of G. sylvestre (100 mg/kg/day) for 1 month. 11 By the second week, the mean blood sugar level was lower among animals receiving the gymnema extract (74 mg/dL) than among the control group (106 mg/dL). This difference was maintained throughout the study. A blood glucose-lowering effect of similar magnitude produced by tolbutamide has been demonstrated. It should be noted that the doses used would be equivalent to a 7 g dose for a typical man. 12 A more dramatic effect was noted when the extract was administered parenterally to rats. 13 Another study showed that on a dose basis (ED50), gymnema was 7- and 6-fold less potent in normal and diabetic rats, respectively, than tolbutamide. 14 Blood glucose was significantly reduced in mice rendered hyperglycemic by daily doses of dexamethasone ( P < 0.05 vs controls). However, no changes in thyroid hormone levels were observed in gymnema-treated mice with corticosteroid-induced diabetes mellitus, suggesting that gymnema may not be effective in thyroid hormone-mediated type 2 diabetes mellitus. 15
Clinical data   Few clinical studies exist; poor reporting of important design features such as blinding or randomization and very high dropout rates reduce the usefulness of their findings. Mean glycosylated hemoglobin (HbA1c ) decreased significantly from baseline (12.8% to 9.5%, P < 0.001) at 6 months in a controlled trial of patients with type 1 diabetes. 16 Study patients received 200 mg gymnema twice daily, in addition to their usual doses of insulin. Insulin dosage and fasting blood glucose were significantly reduced from baseline after 26 to 30 months. Patients receiving placebo had no significant changes from baseline in any of the measured parameters. Significant decreases in HbA1c (12% to 8%, P < 0.001) and fasting blood glucose (174 to 124 mg/dL, P < 0.001) also were observed in a study of 22 patients with type 2 diabetes. 17 Patients received 400 mg/day gymnema in addition to glibenclamide or tolbutamide; 5 patients were able to discontinue sulfonylurea treatment by the end of the study. No significant changes in HbA1c , fasting blood glucose, or lipids were observed in placebo recipients. The use of a gymnema supplement (400 mg leaf extract standardized to 25%) twice daily reduced HbA1c levels in patients with diabetes mellitus type 1 and type 2 in a third study. 18 Mean daily preprandial plasma glucose concentrations were 11% lower (161 vs 144 mg/dL) after 90 days. The greatest glucose-lowering effects were observed in patients with the highest initial HbA1c levels. Mean daily preprandial plasma glucose concentrations in this subset fell by 18% (216 vs 178 mg/dL). A systematic review of herbs and dietary supplements used for glycemic control in diabetes has been conducted. 19 It concluded that the evidence for beneficial effects of G. sylvestre in diabetes is suggestive, although inconclusive given the limited data.
Lipid-lowering
Animal data   A dose-dependent increase in fecal cholesterol and cholic acid-derived bile acid excretion has been demonstrated in rats. 20 A 3-week study showed a decrease in apparent fat digestibility and an increase in excretion of neutral sterols and acidic steroids in rats receiving an extract of G. sylvestre leaves and either a normal or high-fat diet. Total serum cholesterol and triglycerides also were decreased significantly. 21 After 10 weeks, plasma triglycerides were lower in gymnema-fed rats than in controls, but the difference in plasma total cholesterol levels was no longer significant. 22
Clinical data   Reduction in plasma cholesterol, triglycerides, and free fatty acid levels was observed in 2 studies of diabetic patients who received supplements of gymnema in addition to their usual antidiabetic medication (eg, insulin, glibenclamide, or tolbutamide). 16 , 17 In contrast, these levels increased gradually from baseline in the control group patients not taking gymnema. It should be noted that lipid lowering was a secondary endpoint in these studies, which were designed to demonstrate the antidiabetic effects of gymnema.
Weight loss
Animal data   An increase in body weight was significantly suppressed in a long-term study of the administration of G. sylvestre extract in rats fed a high-fat diet. However, in rats receiving a normal diet, no significant suppression of weight gain was observed. 22
Clinical data   Use of a dietary supplement containing G. sylvestre in combination with glucomannan, chitosan, fenugreek, and vitamin C was investigated in obese adults (body mass index 30 kg/m2 or more). 23 Compared with placebo recipients, the treatment group lost significantly more body weight (-2.3 vs 0 kg; P < 0.01), and percentage of body fat and absolute fat mass were significantly reduced ( P < 0.05 and P < 0.001, respectively). Reduction in upper abdominal, waist, and hip circumferences also was demonstrated in patients receiving active treatment.
Suppression of sweet taste   Gymnema extract interferes with the ability of the taste buds to taste sweet and bitter flavors (such as sugar or quinine), but the ability to taste sour, astringent, or pungent substances is maintained.
Animal data   In rats, taste response to sucrose, fructose, lactose, and maltose was markedly suppressed by gurmarin, a protein extracted from G. sylvestre ; response to saccharin sodium was weaker. 24 , 25 Minimal response to sodium chloride, hydrochloric acid, and quinine hydrochloride was noted. 25 Preference for sucrose recovered within 1 or 2 weeks after cessation of gymnema intake. 24
Clinical data   Research reveals no clinical data regarding the use of gymnema for suppression of sweet taste.
Inflammation   Anti-inflammatory properties of gymnema have been demonstrated. Biochemical markers of inflammation, such as γ-glutamyl transpeptidase, superoxide dismutase, and lipid peroxides are enhanced, increasing protection against leukotrienes and free radicals and aiding rapid tissue repair and remodeling.
Animal data   Histamine release from mast cells was inhibited by extracts of G. sylvestre in vitro. 5 Moderate inhibition of carrageenan-induced rat paw edema was induced by an aqueous extract of the leaves of G. sylvestre ; naproxen produced superior inhibition of edema. However, efficacy of gymnema was similar to naproxen in a peritoneal ascites model in mice. Unlike naproxen, gymnema did not inhibit beneficial granuloma formation and the gastric mucosa was not irritated by high doses. 26
Clinical data   Research reveals no clinical data regarding the use of gymnema for inflammation.
Other uses   An alcoholic extract of dried leaves exhibited antibacterial activity against Bacillus pumilis , B. subtilis , Pseudomonas aeruginosa , and Staphylococcus aureus . 27 Gymnemic acids A and B have demonstrated antiviral activity against the influenza virus. Other fractions lacked this activity. 5 A possible application in the prevention of dental plaque formation has been investigated, but systematic studies are lacking to confirm this use. 5
 
Administration & Dosage
Typically, clinical studies investigating antidiabetic effects have used 200 or 400 mg of an extract standardized to contain 25% gymnemic acids administered twice daily.
 
Pregnancy/Lactation
No information on use in pregnancy or lactation was found. Manufacturers of commercial supplements recommend against use during pregnancy. 18
 
Interactions
None well documented.
 
Adverse Reactions
Hypoglycemia may occur.
 
Toxicology
No adverse reactions were reported in a long-term study of insulin-dependent diabetic patients. 16 However, consider the possibility of hypoglycemia. Systolic blood pressure was raised in spontaneously hypertensive rats fed a high sucrose diet. The clinical significance of this finding is unknown. 28
The plant has not been associated with published reports of human toxicity; however, it is possible that as few as 12 tablets of some otc preparations could cause a demonstrable hypoglycemic reaction in humans. Blood urea, uric acid, and hemoglobin levels remained in the normal range in patients receiving gymnema supplements in addition to their usual antidiabetic medication, suggesting the absence of hepato- or nephrotoxicity at normal doses. In an acute toxicity study in mice, no gross behavioral, neurologic, or autonomic effects were observed. The acute LD50 was 3990 mg/kg. The safety ratio (LD50 /ED50 ) was 11 and 16 in normal and diabetic rats, respectively. 14
 
References
 

1. Penso G. Inventory of Medicinal Plants Used In the Different Countries , World Health Organization; 1982.

 

2. Mhaskar KS, Caius JF. Indian Med Res Memoirs . 1930; #16.

 

3. Windholz M, ed. The Merck Index . 10th ed. Rahway, NJ: Merck & Co.; 1983.

 

4. Gymnema sylvestre . Altern Med Rev . 1999;4:46-47. Available at: http://www.thorne.com/pdf/journal/4-1/gymnema_monograph.pdf . Accessed May 12, 2004.

 

5. Porchezhian E, Dobriyal RM. An overview on the advances of Gymnema sylvestre : chemistry, pharmacology and patents. Pharmazie . 2003;58:5-12.  PubMed

 

6. Persaud SJ, Al-Majed H, Raman A, Jones PM. Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability. J Endocrinol . 1999;163:207-212.  PubMed

 

7. Fletcher JI, Dingley AJ, Smith R, Connor M, Christie MJ, King GF. High-resolution solution structure of gurmarin, a sweet-taste-suppressing plant polypeptide. Eur J Biochem . 1999;264:525-533.  PubMed

 

8. Yoshikawa M, Murakami T, Kadoya M, et al. Medicinal foodstuffs. IX. The inhibitors of glucose absorption from the leaves of Gymnema sylvestre R.Br. (Asclepiadaceae): structures of gymnemosides a and b. Chem Pharm Bull . 1997;45:1671-1676.  PubMed

 

9. Shimizu K, Iino A, Nakajima J, et al. Suppression of glucose absorption by some fractions extracted from Gymnema sylvestre leaves. J Vet Med Sci . 1997;59:245-251.  PubMed

 

10. Rahman AU, Zaman K. J Ethnopharmacol . 1989;26:73.

 

11. Gupta SS, et al. Indian J Med Res . 1962;Sep 50:1.

 

12. Gupta SS, Seth CB. Experimental studies on pituitary diabetes. II. Comparison of blood sugar level in normal and anterior pituitary extract induced hyperglycemic rats treated with a few Ayurvedic remedies. Indian J Med Res . 1962;50:708-714.  PubMed

 

13. Gupta SS, Variyar MC. Experimental studies on pituitary diabetes. IV. Effect of Gymnema sylvestre and Coccinia indica against the hyperglycaemic response of somatotropin and corticotropin hormones. Indian J Med Res . 1964;52:200-207.  PubMed

 

14. Chattopadhyay RR. A comparative evaluation of some blood sugar lowering agents of plant origin. J Ethnopharmacol . 1999;67:367-372.  PubMed

 

15. Gholap S, Kar A. Effects of Inula racemosa root and Gymnema sylvestre leaf extracts in the regulation of corticosteroid induced diabetes mellitus: involvement of thyroid hormones. Pharmazie . 2003;58:413-415.  PubMed

 

16. Shanmugasundaram ERB, Rajeswari G, Baskaran K, Rajesh Kumar BR, Radha Shanmugasundaram K, Kizar Ahmath B. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J Ethnopharmacol . 1990;30:281-294.  PubMed

 

17. Baskaran K, Kizar Ahamath B, Radha Shanmugasundaram K, Shanmugasundaram ER. Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J Ethnopharmacol . 1990;30:295-305.  PubMed

 

18. Joffe DJ, Freed SH. The effect of extended release Gymnema sylvestre leaf extract alone or in combination with oral hypoglycemics or insulin regimens for type 1 and type 2 diabetes. Diabetes in Control Newsletter . 2001;76.

 

19. Yeh GY, Eisenberg DM, Kaptchuk TJ, Phillips RS. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care . 2003;26:1277-1294.  PubMed

 

20. Nakamura Y, Tsumura Y, Tonogai Y, Shibata T. Fecal steroid excretion is increased in rats by oral administration of gymnemic acids contained in Gymnema sylvestre leaves. J Nutr . 1999;129:1214-1222.  PubMed

 

21. Shigematsu N, Asano R, Shimosaka M, Okazaki M. Effect of administration with the extract of Gymnema sylvestre R.Br leaves on lipid metabolism in rats. Biol Pharm Bull . 2001;24:713-717.  PubMed

 

22. Shigematsu N, Asano R, Shimosaka M, Okazaki M. Effect of long-term administration with Gymnema sylvestre R. Br on plasma and liver lipid in rats. Biol Pharm Bull . 2001;24:643-649.  PubMed

 

23. Woodgate DE, Conquer JA. Effects of a stimulant-free dietary supplement on body weight and fat loss in obese adults: a six-week exploratory study. Curr Ther Res . 2003;64:248-262.

 

24. Katsukawa H, Imoto T, Ninomiya Y. Induction of salivary gumarin-binding proteins in rats fed gymnema-containing diets. Chem Senses . 1999;24:387-392.  PubMed

 

25. Harada S, Kasahara Y. Inhibitory effect of gurmarin on palatal taste responses to amino acids in the rat. Am J Physiol Regul Integr Comp Physiol . 2000;278:R1513-R1517.  PubMed

 

26. Diwan PV, Margaret I, Ramakrishna S. Influence of Gymnema sylvestre on inflammation. Inflammopharmacology . 1995;3:271-277.

 

27. Satdive RK, Abhilash P, Fulzele DP. Antimicrobial activity of Gymnema sylvestre leaf extract. Fitoterapia . 2003;74:699-701.  PubMed

 

28. Preuss HG, Jarrell ST, Scheckenbach R, Lieberman S, Anderson RA. Comparative effects of chromium, vanadium and Gymnema sylvestre on sugar-induced blood pressure elevations in SHR. J Am Coll Nutr . 1998;17:116-123.  PubMed