Gymnema

Scientific Name(s): Gymnema inodum, Gymnema montanum, Gymnema sylvestre (Retz.) Schult., Periploca sylvestris
Common Name(s): Gurmar, Gurmarbooti, Kogilam, Madhunashini, Mangala gymnema, Merasingi, Meshashringi, Meshavalli, Miracle plant, Periploca of the woods, Podapatri, Ram’s horn, Sarkaraikolli, Shardunika, Sirukurinja, Small Indian ipecac, Vishani

Medically reviewed by Drugs.com. Last updated on Jan 22, 2024.

Clinical Overview

Use

The plant has been used in traditional medicine, most notably to control blood glucose, which seems to have the strongest evidence of its historical uses. Use as a lipid-lowering agent, for weight loss, and for the inhibition of caries have also been investigated, primarily in rodent studies. However, limited clinical information is available to support the use of gymnema for any indication.

Dosing

Limited controlled studies exist. Clinical studies investigating antidiabetic effects have typically used 200 or 400 mg extract daily standardized to contain 25% gymnemic acids.

Contraindications

None established.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

A case report of hepatotoxicity exists.

Toxicology

Information is lacking.

Scientific Family

• Asclepiadaceae (milkweed)

Botany

G. sylvestre is a woody, climbing plant indigenous to the tropical forests of central and southern India. Distribution of gymnema is worldwide, and it is recognized in the traditional medicinal literature of many countries, including Australia, Japan, and Vietnam. The opposite, elliptic/ovate leaves are most commonly used, but the stem also appears to possess some pharmacologic activity. The plant bears small, yellowish flowers. Gymnema is also known as Asclepias geminata Roxb., Gymnema melicida Edg., and Pinus sylvestris Willd. Gymnema montanum has also been investigated.Kanetkar 2007, Leach 2007, PLANTS 2011

History

Gymnema has played an important role in the traditional Ayurvedic medical system for centuries, primarily confined to the management of diabetes mellitus and similar hypo/hyperglycemic conditions. The leaves have also 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. Chewing the leaves destroys the ability to discriminate sweet taste, giving it the common Hindi name of gurmar or "sugar destroyer." The plant has been used alone and as a component of the Ayurvedic compound Tribang shila, a mixture of tin, lead, zinc, G. sylvestre leaves, neem (Melia azadirachta) leaves, Enicostemma littorale, and jambul (Eugenia jambolana) seeds. As early as 1930, the pharmacologic effect of the plant was investigated. The plant is available in a number of commercial over-the-counter herbal products.Leach 2007, Mhaskar 1930, Windholz 1983

Chemistry

Gymnemic acids, a group of triterpenoid saponins, are the main class of chemical constituents isolated from G. sylvestre and are thought to be responsible for the observed antidiabetic activity. 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, and high performance liquid chromatography methods for standardization have been described.

Also present in gymnema extracts are gymnemasaponins, a group of antisweet principles with a novel D-glucoside structure. The structure of gurmarin, another antisweet agent found in gymnema, has been elucidated. Gymnemosides have been isolated from alcoholic extracts of G. sylvestre leaves. Other constituents include flavones, anthraquinones, chlorophylls, phytin, resins, quercitol, alkaloids, and tannic, formic, and butyric acids.Fletcher 1999, Kanetkar 2007, Porchezhian 2003, Puratchimani 2004, Raju 2006, Yoshikawa 1997, Zhu 2008

Uses and Pharmacology

Anti-inflammatory

Histamine release from mast cells was inhibited by extracts of G. sylvestre in vitro.(Porchezhian 2003) Moderate inhibition of carrageenan-induced rat paw edema occurred with an aqueous extract of G. sylvestre leaves; naproxen produced superior inhibition of edema. However, efficacy of gymnema was similar to that of naproxen in a peritoneal ascites model in mice. Unlike naproxen, gymnema did not inhibit beneficial granuloma formation; gastric mucosa was not irritated by high doses.(Diwan 1995)

Antimicrobial

An alcoholic extract of dried leaves exhibited antibacterial activity against Bacillus pumilis, Bacillus subtilis, Pseudomonas aeruginosa, and Staphylococcus aureus.(Satdive 2003) Gymnemic acids A and B have demonstrated antiviral activity against the influenza virus. Other fractions lacked this activity.(Porchezhian 2003) A possible application in the prevention of dental plaque formation has been investigated, but systematic studies are lacking to confirm this use.(Porchezhian 2003)

Cancer

Radical scavenging and cytotoxic and antigenotoxic effects have been demonstrated for gymnema extracts, possibly due to phenolic and specific saponin content.(Khanna 2009, Ohmori 2005, Ramkumar 2010)

Diabetes

Studies suggest the hypoglycemic effects of gymnema extracts operate through a number of possible mechanisms, including reduced uptake of glucose in the small intestine, improved glycolysis, glucogen synthesis and gluconeogenesis, and stimulation of insulin release from islets of Langerhans.(Leach 2007, Liu 2009, Persaud 1999, Shimizu 1997)

Animal data

A number of studies have evaluated the effects of G. sylvestre on blood sugar in animals, often in comparison with glibenclamide or tolbutamide. Most studies reported decreased blood glucose concentrations in diabetic rats.(Chattopadhyay 1999, Gholap 2003, Gupta 1962, Gupta 1964, Rahman 1989, Ramkumar 2008, Ramkumar 2009, Yadav 2010) Decreased lipid peroxidation and oxidative stress have also been demonstrated in rats.(Ananthan 2004, Ramkumar 2004, Ramkumar 2008, Ramkumar 2009, Ramkumar 2009) In addition, taste response to sucrose, fructose, lactose, and maltose in rats was markedly suppressed by gurmarin, a protein extracted from G. sylvestre.(Harada 2000, Katsukawa 1999)

Clinical data

A good level of evidence (Grade B) for use in type 1 and type 2 diabetics has been noted, however robust clinical trials are still lacking. Few methodologically sound clinical studies exist.(Leach 2007, Pothuraju 2014, Ulbricht 2011) Early, small clinical studies found decreases in mean glycosylated hemoglobin (HbA_1c), fasting blood glucose, and mean daily preprandial plasma glucose for patients with type 1 and 2 diabetes receiving gymnema extracts in addition to their usual medication.(Baskaran 1990, Joffe 2001, Shanmugasundaram 1990)

An open-label, quasi-experimental designed study conducted in 58 type 2 diabetics in India investigated the effects of G. sylvestre leaf extract (250 mg twice daily for 3 months) on hyperglycemia and dyslipidemia when given as an adjuvant to conventional antidiabetic medications. Patients in the control group who received no adjunctive treatment with G. sylvestre experienced worsening of secondary complications, anthropomorphic measurements, fasting blood glucose (FBG), HbA_1c, and insulin resistance, as well as an increase in oral hypoglycemic, antihypertensive, and statin medications, whereas the treatment group did not. In contrast to controls, patients administered G. sylvestre experienced statistically significant improvements from baseline in several biochemical measures including mean FBG (−26 mg/dL; P<0.002), HbA_1c (−1%; P<0.000), and triglycerides (−25 mg/dL; P<0.049), as well as significant improvements in insulin resistance, apolipoprotein B, and kidney function. Additionally, 2 patients (10%) in the treatment group were able to discontinue oral hypoglycemic medications, compared to none in the control group.(Kumar 2010) Administration of a high-molecular weight fresh extract of G. sylvestre leaves (500 mg twice daily for 60 days) administered to 11 type 2 diabetics led to significant reductions in mean FBG and postprandial blood glucose by 43 and 55 mg/dL (P<0.005 and P<0.02), respectively. Correspondingly, significant increases were also observed in mean serum insulin (8 microunits/mL, P<0.001) and C-peptide (149 picomol/L, P<0.05).(Al-Romaiyan 2010)

In overweight and obese patients with untreated impaired glucose sensitivity, results from a 12-week double-blind, randomized, placebo-controlled study (N=30) showed that a significantly higer proportion of patients (46.7%) taking G. sylvestre 300 mg twice daily achieved normal HbA_1c compared to placebo (0%; P=0.003). The significant improvements from baseline seen in the treatment group in 2-hour post-load plasma glucose, low-density lipoprotein-cholesterol, body weight, and insulin sensitivity were not significantly different from changes observed in the placebo group. The prevalence of adverse events was similar between groups with headache and GI complaints reported most commonly.(Gaytán Martínez 2021)

A systematic review identified 10 controlled, interventional studies (N=419) investigating the effect of G. sylvestre supplementation on glycemic control in adults with type 2 diabetes. The studies were published between 1988 and 2017: 2 were randomized, 2 were noted as double-blind, and no indication of the type of control group was provided for any of the included studies. The value of the results are limited as outcomes were reported only for post-treatment compared to baseline; no between-group results were provided. Compared to baseline, the highly heterogenous pooled data from all 10 studies reflected a statistically significant but clinically small improvement in fasting blood sugar (−1.57 mg/dL; P<0.00001) with G. sylvestre. Similarly, statistically significant improvements were reported with gymnema on postprandial blood glucose, HbA_1c, triglycerides, and total cholesterol compared to baseline levels; however, heterogeneity was very high for all comparisons.(Devangan 2021)

A 2014 systematic review of G. sylvestre used for obesity and diabetes identified the Al-Romaiyan, 2010 study plus one additional trial. The latter reported an additive effect of combining G. sylvestre extract with hydroxycitric acid that resulted in improved weight, body mass index, and lipid parameters as well as urinary fatty acid oxidation biomarkers.(Pothuraju 2014)

Lipid-lowering

Animal data

A dose-dependent increase in fecal cholesterol and cholic acid-derived bile acid excretion has been demonstrated in rats.(Nakamura 1999) 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 were also decreased.(Shigematsu 2001) After 10 weeks, plasma triglycerides were lower in gymnema-fed rats compared with controls, but there was no difference in plasma total cholesterol levels.(Shigematsu 2001) In diabetic rats, improved lipid profiles were observed with gymnema extract and gymnemic triacetate.(Daisy 2009, Luo 2007, Ramkumar 2008)

Clinical data

Reduction in plasma cholesterol, triglycerides, and free fatty acid levels was observed in limited studies of diabetic patients who received supplements of gymnema in addition to their usual antidiabetic medication (eg, insulin, glibenclamide, tolbutamide).(Baskaran 1990, Kumar 2010, Shanmugasundaram 1990) Lipid lowering was a secondary end point in these studies, which were designed to demonstrate the antidiabetic effects of gymnema.

Ophthalmic

A combination product containing G. sylvestre extracts was protective against sugar-induced cataracts in rats.(Moghaddam 2005)

Weight loss

Animal data

Increases in body weight were suppressed in a long-term study of the administration of G. sylvestre extract to rats.(Luo 2007, Shigematsu 2001) Conversely, in another rodent study, loss of weight was inhibited by gymnema extracts.(Ramkumar 2009)

Clinical data

Decreased body weight has been demonstrated in studies using combinations of various dietary supplements, including G. sylvestre with chitosan, fenugreek, and vitamin C, and gymnema with niacin-chromium complex. The resultant weight loss cannot be attributed to a single ingredient.(Preuss 2004, Woodgate 2003) In contrast to weight gain experienced by the control group, suppression of weight gain was observed in a quasi-experimental study in type 2 diabetics who received adjunctive use of G. sylvestre extract.(Kumar 2010)

Dosing

Clinical studies investigating antidiabetic effects have typically used 200 or 400 mg extract daily standardized to contain 25% gymnemic acids.Baskaran 1990, Joffe 2001, Preuss 2004, Shanmugasundaram 1990

Diabetes

A total daily dose of 500 to 1,000 mg/day of leaf extract given in twice daily divided doses has been administered for a duration of 2 or 3 months in clinical trials.Al-Romaiyan 2010, Kumar 2010

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.Joffe 2001

Interactions

None well documented.

Adverse Reactions

Taste alteration is known to be a major side effect with gymnema as it tends to reduce the perception of sweetness and increase that of bitterness.Ulbricht 2011 A case report of reversible hepatotoxicity was attributed to the consumption of G. sylvestre as a tea. Toxicity was evident by laboratory indices and histology.Shiyovich 2010 No adverse reactions were reported in 1 long-term clinical study.Shanmugasundaram 1990 Allergic cross-reactivity may theoretically occur in individuals allergic to plants in the milkweed family (Asclepiadaceae).Ulbricht 2011

Systolic blood pressure was raised in spontaneously hypertensive rats fed a high sucrose diet, but the clinical importance of this finding is unknown.Preuss 1998

Toxicology

In a short-term toxicity study in mice, no gross behavioral, neurologic, or autonomic effects were observed. The acute median lethal dose (LD₅₀) was 3,990 mg/kg, and the safety ratio (LD₅₀/median effective dose) was 11 and 16 in normal and diabetic rats, respectively.Chattopadhyay 1999

Index Terms

• Asclepias geminata Roxb.
• Gymnema melicida Edg.
• Pinus sylvestris Willd.

References

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