Diabetes (type 1 and 2), hypoglycemia, and obesity.
Mechanism of Action
Numerous active phytoconstituents including a group of triterpene saponins1,2 known as gymnemic acids,3 gymnemasaponins, and the polypeptide gurmarin4 have been identified in Gymnema and credited with various antioxidant, hypoglycemic, and beta cell–regenerative effects.
Gymnemic acids are a class of chemical compounds isolated from the leaves that are considered sweetness inhibitors, because after chewing the leaves, solutions sweetened with sugar taste like water.5 These acids suppress the sweetness of most of sweeteners including intense artificial sweeteners such as aspartame and natural sweeteners such as thaumatin. The antisweet activity is reversible, but sweetness recovery on the tongue can take more than 10 minutes.6
More than 20 homologs of gymnemic acid are known, the central structure of which is the aglycone gymnemagenin.7 Gymnenagenins may inhibit the glycation of proteins8 and inhibit sodium-dependent glucose transporters9 that are found in high levels in brush-border membranes of intestinal epithelial cells. Animal studies suggest that the antioxidant effects of Gymnema occur via reduced lipid peroxidation in the serum, liver, and kidneys and support hepatic glutathione peroxidase and serum glutamate pyruvate transaminase levels10, among other effects.
Gymnema extracts may promote the production of insulin in weak or damaged beta cells11,12,13 and possibly increase the number of pancreatic beta cells and islets of Langerhans14,15,16 according to histological assessments in diabetic animals. Conduritol A is one Gymnema constituent credited with beta cell regeneration.17 One mechanism of beta cell function seems to be via an increase in Ca(2+) influx through voltage-gated calcium channels and protein kinase activation,18 leading to an increase in intracellular calcium and thereby insulin secretion.19 Contrary to some hypotheses that insulin secretion is the result of beta cell destruction, no damage to islets was seen.
Modern research has focused on the hypoglycemic, hypolipidemic, metabolism supportive, diuretic, and beta cell–regenerating actions of Gymnema.20 Both animal and a few human studies have shown Gymnema to have antiobesity and antidiabetic properties and to significantly reduce body weight and improve laboratory markers of glycemic control.
Gymnema has been shown to improve numerous biochemical markers of inflammation and glycemic and metabolic control in diabetic animals. Dosages of 120–200 mg/kg of various Gymnema extracts are shown to improve a wide array of metabolic markers in animal models of diabetes in approximately 1 month. In summary, positive effects have been demonstrated on body mass index; blood pressure; heart rate; hemodynamic parameters; serum leptin; insulin; glucose; lipids including lactate dehydrogenase, low-density lipoprotein-C, total cholesterol, triglycerides, and apolipoprotein levels; lipid peroxide levels; myocardial apoptosis; antioxidant enzymes; and organ and visceral fat pad weights. In histopathological studies, cardiac Na(+)/K(+)-ATPase and antioxidant enzymes levels were significantly decreased.21,22,23 Histopathological assessments in these animal studies showed no pathological changes to be associated with the use of Gymnema preparations.
Human pilot studies have shown Gymnema to increase insulin and C-peptide release from human beta cells and to significantly reduces fasting and postprandial blood glucose.24 One pilot study with type II diabetics showed Gymnema to improve polyphagia, fatigue, and blood glucose in both fasting and postprandial situations and normalize glycosylated hemoglobin and lipid profiles at a dose of 500 mg/day.25 Another human pilot investigation dosed medicated diabetic patients with Gymnema at a dose of 400 mg/day in tandem with conventional oral hypoglycemic agents. After 18–20 months a significant reduction in blood glucose, glycosylated hemoglobin, and glycosylated plasma proteins was demonstrated, and 5 of the 22 subjects were able to discontinue their pharmaceuticals altogether, and the majority decreased their dosage of prescription drugs.26
One randomized controlled trial dosed 400 mg of Gymnema to insulin-dependent diabetics and reported that fasting glucose and hemoglobin A1c was reduced, along with significant reductions in serum lipids to near normal levels. No such improvements were seen in a control group receiving insulin alone. Researchers hypothesize that Gymnema may be able to regenerate or revitalize residual beta cells in the pancreas of insulin-dependent diabetics based on the histological findings in animals, combined with the clinical outcomes and laboratory findings in human subjects.27
Safety in Pregnancy and Breastfeeding
There are no published studies specifically investigating Gymnema in pregnancy or lactation.
There has been one anecdotal report associating the use of Gymnema by humans to induce liver injury.28 However, the various human pilot and other studies have not reported any significant toxicity, and there are also reports of hepatoprotection from the triterpenoids saponins.29
An animal toxicity study was conducted wherein Gymnema was determined to be safe when administered at high doses for 1 year.30
Doses between 120 and 500 mg/kg have been used in animal studies; however, some human trials have dosed only 500 mg of total of a quantified Gymnema marker compound.
Gymnema is generally considered safe and is dosed at 400–600 mg/daily, standardized to 24% Gymnemic acids.
Gymnema sylvestre is referred to as gurmar in Hindi. This term translates as “sugar destroyer” because of its ability to abolish the sweet taste of various foods as well as control sugar cravings. It has been used for thousands of years to treat obesity as well as the symptoms of diabetes, arthritis, anemia, osteoporosis, hypercholesterolemia, heart disease, asthma, constipation, microbial infections, indigestion, and general systemic inflammation.31
1 World J Microbiol Biotechnol. 2012;28(2):741–7. Abiotic elicitation of gymnemic acid in the suspension cultures of Gymnema sylvestre. Ch B, Rao K, Gandi S, Giri A.
2 Molecules. 2014;19(8):10956–81. Triterpenoids from Gymnema sylvestre and their pharmacological activities. Fabio GD.
3 J Clin Biochem Nutr. 2007;41(2):77–81. Gymnema sylvestre: A Memoir. Kanetkar P, Singhal R, Kamat M.
4 Biomed Res Int. 2014;2014:830285. Phytochemical and pharmacological properties of Gymnema sylvestre: an important medicinal plant. Tiwari P, Mishra BN, Sangwan NS.
6 Chin J Nat Med. 2014;12(4):300–4. Chemical constituents from the stems of Gymnema sylvestre. Liu Y, et al.
7 Less Common High-Potency Sweeteners. Alternative Sweeteners. 2nd edn., New York: Marcel Dekker; 1991. Kinghorn A, Compadre C.
8 Chin J Nat Med. 2014;12(4):300–4. Chemical constituents from the stems of Gymnema sylvestre. Liu Y, et al.
9 J Agric Food Chem. 2014;62(25):5925–31. Gymnemic acids inhibit sodium-dependent glucose transporter 1. Wang Y, et al.
10 J Agric Food Chem. 2012;60(10):2517–24. Hypoglycemic activity of Gymnema sylvestre extracts on oxidative stress and antioxidant status in diabetic rats. Kang MH, Lee MS, Choi MK, Min KS, Shibamoto T.
11 J Ethnopharmacol. 1990;30:281–94. Use of Gymnema sylvestre leaf extracts in the control of blood glucose in insulin-dependant diabetes mellitus. Shanmugrasundaram ERB, et al.
12 J Ethnopharmcol. 1990;30:295–305. Antidiabetic effect of a leaf extract from Gymnema syvestre in non-insulin dependent diabetes mellitus patients. Baskaran K, et al.
13 Phytother Res. 2013;27(7):1006–11. A novel extract of Gymnema sylvestre improves glucose tolerance in vivo and stimulates insulin secretion and synthesis in vitro. Al-Romaiyan A, King AJ, Persaud SJ, Jones PM.
14 J Ethnopharmacol. 1990;30:265–79. Possible regeneration of the islets of Langerhans in streptozotocin-diabetic rats given Gymnema sylvestre leaf extracts. Shanmugasundaram ERB, et al.
15 Phytomedicine. 2010;17(13):1033–9. In vitro callus and in vivo leaf extract of Gymnema sylvestre stimulate β-cells regeneration and anti-diabetic activity in Wistar rats. Ahmed AB, Rao AS, Rao MV.
16 Morfologiia. 2008;133(1):60–4. Structural alterations in pancreatic islets in streptozotocin-induced diabetic rats treated with of bioactive additive on the basis of Gymnema sylvestre. Snigur GL, Samokhina MP, Pisarev VB, Spasov AA, Bulanov AE.
17 Zhongguo Zhong Yao Za Zhi. 2008;33(24):2961–5. Experimental [corrected] study of hypoglycemic activity of conduritol A of stems of Gymnema sylvestre. Wei JH, Zhen HS, Qiu Q, Chen J, Zhou F.
18 Diabetes Obes Metab. 2012;14(12):1104–13. Investigation of intracellular signalling cascades mediating stimulatory effect of a Gymnema sylvestre extract on insulin secretion from isolated mouse and human islets of Langerhans. Al-Romaiyan A, Liu B, Docherty R, Huang GC, Amiel S, Persaud SJ, Jones PM.
19 Cell Physiol Biochem. 2009;23(1–3):125–32. Characterisation of the insulinotropic activity of an aqueous extract of Gymnema sylvestre in mouse beta-cells and human islets of Langerhans. Liu B, Asare-Anane H, Al-Romaiyan A, Huang G, Amiel SA, Jones PM, Persaud SJ.
20 Molecules. 2013;18(12):14892–919. C-4 gem-dimethylated oleanes of Gymnema sylvestre and their pharmacological activities. Di Fabio G, et al.
21 Indian J Pharmacol. 2012;44(5):607–13. Evaluation of antiobesity and cardioprotective effect of Gymnema sylvestre extract in murine model. Kumar V, Bhandari U, Tripathi CD, Khanna G.
22 Indian J Pharm Sci. 2014;76(4):315–22. Protective effect of Gymnema sylvestre ethanol extract on high fat diet-induced obese diabetic Wistar rats. Kumar V, Bhandari U, Tripathi CD, Khanna G.
23 Drug Res (Stuttg). 2013;63(12):625–32. Anti-obesity effect of Gymnema sylvestre extract on high fat diet-induced obesity in Wistar rats. Kumar V, Bhandari U, Tripathi CD, Khanna G.
24 Phytother Res. 2010;24(9):1370–6. A novel Gymnema sylvestre extract stimulates insulin secretion from human islets in vivo and in vitro. Al-Romaiyan A, et al.
25 J Diet Suppl. 2010;7(3):273–82. An open label study on the supplementation of Gymnema sylvestre in type 2 diabetics. Kumar SN, Mani UV, Mani I.
26 J Ethnopharmacol. 1990;30(3):295–300. Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. Baskaran K, et al.
27 J Ethnopharmacol. 1990;30(3):281–94. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. Shanmugasundaram ER, et al.
28 Am J Med Sci. 2010;340(6):514–7. Toxic hepatitis induced by Gymnema sylvestre, a natural remedy for type 2 diabetes mellitus. Shiyovich A, Sztarkier I, Nesher L.
29 Planta Med. 2013;79(9):761–7. Hepatoprotective phenolic glycosides from Gymnema tingens. Tian J, Ma QG, Yang JB, Wang AG, Ji TF, Wang YG, Su YL.
30 Shokuhin Eiseigaku Zasshi. 2004;45(1):8–18. Gymnema sylvestre leaf extract: a 52-week dietary toxicity study in Wistar rats. Ogawa Y, Sekita K, Umemura T, Saito M, Ono A, Kawasaki Y, Uchida O, Matsushima Y, Inoue T, Kanno J.
31 Biomed Res Int. 2014;2014:830285. Phytochemical and pharmacological properties of Gymnema sylvestre: an important medicinal plant. Tiwari P, Mishra BN, Sangwan NS.