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Gymnema (Gymnema sylvestre R. Br.) Natural Standard Monograph (www.naturalstandard.com) Copyright © 2008. Synonyms/Common Names/Related Substances: Asclepiadaceae (family), Asclepias geminata Roxb., Gemnema melicida, GS4 (water soluble extract of the leaves), gur-mar, gurmar, gurmarbooti, Gymnema inodum, Gymnema montanum, Gymnema sylvestre, kogilam, madhunashini, mangala gymnema, merasingi, meshashringi, meshavalli, miracle plant, periploca of the woods, Periploca sylvestris, podapatri, Proβeta®, ram's horn, sarkaraikolli, shardunika, sirukurinja, small Indian ipecac, vishani. Brief Background: Gymnema leaves have been used for more than 2,000 years in India to treat madhu meha, or "honey urine." It has been used alone and as a component of the Ayurvedic medicinal compound, "Tribang shila," a mixture of tin, lead, zinc, Gymnema sylvestre leaves, neem leaves (Melia azadirachta), Enicostemma littorale, and jambul seeds (Eugenia jambolana). Preliminary human evidence suggests that gymnema may be efficacious for the management of serum glucose levels in type 1 and type 2 diabetes, as an adjunct to conventional drug therapy, for up to 20 months. Gymnema appears to lower serum glucose and glycosylated hemoglobin (HbA1c) levels following chronic use, but may not have significant acute effects (1). Some of the available research has been conducted by authors affiliated with manufacturers of gymnema products. High-quality human trials are lacking in this area (2;3;4). There is also early evidence suggesting possible efficacy of gymnema as a lipid-lowering agent. Gymnema was shown in one study to possess antimicrobial action against Bacillis pumilis, B. subtilis, Pseudomonas aeruginosa, and Staphylococcus aureus but not against E. coli and Proteus vulgaris (5). Scientific Evidence for Common/Studied Uses: Indication Evidence Grade Type 1 diabetes mellitus B Type 2 diabetes mellitus B Hyperlipidemia C Weight loss C Historical or Theoretical Indications that Lack Sufficient Evidence: Allergy, antioxidant, antimicrobial (5), aphrodisiac, cancer, cardiovascular disease, constipation, cough, dental caries, digestive stimulant, diuresis, gout (13), hepatoprotection, hypertension (14; 15), laxative, liver disease, malaria, metabolic disorders, obesity, rheumatoid arthritis (13), snake venom antidote (16), stomach ailments, uterine stimulant, viral infection. Expert Opinion and Folkloric Precedent: Gymnema leaves have been used for more than 2,000 years in India to treat madhu meha, or "honey urine." It has been used alone and as a component of the Ayurvedic medicinal compound, "Tribang shila," a mixture of tin, lead, zinc, Gymnema sylvestre leaves, neem leaves (Melia azadirachta), Enicostemma littorale, and jambul seeds (Eugenia jambolana). Traditional healers observed that chewing the leaves of gymnema resulted in a reversible loss of sweet-taste perception. The plant has also been used in African healing traditions; for example, Tanzanian healers used it as an aphrodisiac. Other traditional applications include use as an anti-malarial agent, digestive stimulant, laxative, diuretic, and snake venom antidote. Brief Safety Summary: Possibly Unsafe: When used in patients taking other hypoglycemic agents, because of possible potentiation of effects. Hypoglycemic effects associated with gymnema have been noted in both diabetic and non-diabetic individuals (17). When used in patients taking weight loss agents because there may be a potential for additive effects (18). General: Listed doses are based on those most commonly used in available trials, on historical practice, or on manufacturer recommendations. However, with natural products it is often not clear what the optimal doses are to balance efficacy and safety. Preparation of products may vary from manufacturer to manufacturer, and from batch to batch within one manufacturer. Because it is often not clear what the active components of a product are, standardization may not be possible, and the clinical effects of different brands may not be comparable. Standardization: At least one manufacturer offers an extract of gymnema standardized to 25% gymnemic acid, but this extract has not yet been clinically evaluated. An ethanolic acid-precipitated extract from gymnema, labeled GS4, has been used in human trials (1; 19). GS4 has since been patented as the product Proβeta®, by a research team who has conducted some of the research in this area. According to the makers of Proβeta®, the preparation is standardized to possess a specific biological result, as measured by a test developed by the company that evaluates "pancreotropic®" effects. Examples of other standardized commercially available products include Beta Fast GXR (Informulab): 400mg standardized to 25% gymnemic acids; Gymnesyl (Nature's Herbs): extract standardized for 150mg of crude gymnemic acids; and Gymnema (Nature's Way): 260mg standardized to 75% gymnemic acids. Dosing Adult (age ≥18): Oral: Hyperlipidemia: In one study, patients with type 2 diabetes mellitus received 400mg of gymnema extract for 18-20 months (1). Type 1 diabetes: 200mg extract GS4 orally, twice daily (19), under careful continuation of insulin, has been used. Doses of insulin or other concomitant hypoglycemic drugs may have to be adjusted or discontinued under the supervision of a healthcare professional. Type 2 diabetes: 200mg extract GS4 has been taken orally, twice daily (1), or 2mL of an aqueous decoction (10g shade-dried powdered leaves per 100mL), three times daily (17). Doses of insulin or other concomitant hypoglycemic drugs may have to be adjusted or discontinued under the supervision of a healthcare professional. 6-15 drops of Gymnema sylvestre "Q" with 1/4 cup of water, has been taken 2-4 times daily for six months (16). Weight loss: Gymnema sylvestre extract (GSE) 400mg has been studied in combination with a watersoluble, calcium-potassium salt of (-)-hydroxycitric acid (HCA-SX) 4,667mg and niacin-bound chromium (NBC) 4mg (18). Note: The manufacturer PharmaTerra recommends the dose for their product Proβeta® (GS4) to be two 250mg capsules taken twice daily at mealtimes (for adults weighing >100 pounds), or one 250mg capsule taken twice daily at mealtimes (for adults weighing <100 pounds). Children (age <18): Insufficient available evidence. Toxicology: Insufficient available evidence. Allergy: There is a lack of allergy/hypersensitivity to gymnema reported in the available literature. In theory, allergic cross-reactivity may occur to members of the Asclepiadaceae (milkweed) family. Adverse Effects: General: Aside from hypoglycemia and potentiation of the effects of hypoglycemic drugs following chronic use of gymnema, no clinically significant adverse effects have been associated with oral gymnema in the available literature, in studies up to 20 months in duration. Endocrine: Multiple animal studies have reported hypoglycemic effects associated with ingestion of gymnema leaves. Gymnema reduced hyperglycemia in experimentally and spontaneously diabetic rats and rabbits (20;21;22;23;24;25;26), as well as in normal and diabetic humans (1; 16;17;19;23). One subject with brittle diabetes had to discontinue gymnema in a clinical trial due to repeated hypoglycemic episodes (19). Hypoglycemic effects have been noted in both diabetic and non-diabetic individuals (17). Oral (taste effects): Gymnema has been reported to possess a sweet taste-suppressing effect, attributed to the peptide gurmarin (6;7;27;28;29). Historically, this phenomenon has been observed, prompting the Hindi name gurmar or "sugar destroyer." Precautions/Warnings/Contraindications: Use cautiously in diabetic patients using hypoglycemic medications, due to possible potentiation of effects. Serum glucose levels should be monitored, and doses of concomitant hypoglycemic drugs may require adjustment under the supervision of a healthcare professional. Hypoglycemia may also occur in non-diabetic patients (17). Use cautiously in patients taking weight loss agents because there may be a potential for additive affects. Gymnema sylvestre extract (GSE) has been used in combination with other weight loss agents (hydroxycitric acid and niacin-bound chromium), although a mechanism of action is unclear (18). Use cautiously in patients taking antilipemic agents because there may be a potential for additive effects. Reductions in levels of serum triglycerides, total cholesterol, very low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) have been observed in animals following administration of gymnema (30;31). Pregnancy & Lactation: Not recommended due to insufficient available safety information. Gymnema/Drug Interactions: Antidiabetic agents: Gymnema may potentiate the effects of hypoglycemic drugs in diabetic patients (1;19;19). Doses of such medications may therefore need adjustment. Serum glucose levels should be monitored, and doses of concomitant hypoglycemic drugs may require adjustment under the supervision of a healthcare professional. Multiple animal studies have reported hypoglycemic effects associated with the ingestion of gymnema leaves. Gymnema reduced hyperglycemia in experimentally and spontaneously diabetic rats and rabbits (20;21;22;23;24;25;26), as well as in normal and diabetic humans (1;16;17;19;23). Antilipemic agents: Reductions in levels of serum triglycerides, total cholesterol, very low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) have been observed in animals following administration of gymnema (30;31). A study of gymnema in type 2 diabetes patients reported decreased cholesterol and triglyceride levels as a secondary outcome (1). Concomitant use of gymnema with other lipid lowering agents may potentiate these effects. Antiobesity agents: Human study has investigated Gymnema sylvestre extract (GSE) 400mg in combination with other agents for obesity, although a mechanism of action is unclear (18). Gymnema/Herb/Supplement Interactions: Antilipemics: Reductions in levels of serum triglycerides, total cholesterol, very low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) have been observed in animals following administration of gymnema (30;31). A study of gymnema in type 2 diabetes patients reported decreased cholesterol and triglyceride levels as a secondary outcome (1). Concomitant use of gymnema with other lipid lowering agents may potentiate these effects. Antiobesity herbs and supplements: Human study has investigated Gymnema sylvestre extract (GSE) 400mg in combination with other agents for obesity, although a mechanism of action is unclear (18). Appetite suppressants: Human study has investigated Gymnema sylvestre extract (GSE) 400mg in combination with other agents for obesity, although a mechanism of action is unclear (18). Chromium: Human study has investigated Gymnema sylvestre extract (GSE) 400mg in combination with niacin bound chromium, although a mechanism of action is unclear (18). Fat soluble vitamins: In an animal study, absorption of oleic acid (a fatty acid) was decreased by gymnema (32). It is unknown whether gymnema exerts these effects in humans, or affects the absorption of other nutritionally important lipids or fat-soluble vitamins (A,D,E,K). Garcinia: Human study has investigated Gymnema sylvestre extract (GSE) 400mg in combination with hydroxycitric acid, a component of garcinia (18). Hypoglycemics: Gymnema may potentiate the effects of hypoglycemic herbs or supplements in diabetic patients (1;19). Doses of these agents may therefore need adjustment. Serum glucose levels should be monitored, and doses of concomitant hypoglycemic agents may require adjustment under the supervision of a healthcare professional. Multiple animal studies have reported hypoglycemic effects associated with ingestion of gymnema leaves. Gymnema reduced hyperglycemia in experimentally and spontaneously diabetic rats and rabbits (20; 21;22;23;24;25;26), as well as in normal and diabetic humans (1;16;17;19;23). Gymnema/Food Interactions: Fatty foods: In an animal study, absorption of oleic acid (a fatty acid) was decreased by gymnema (32). It is unknown whether gymnema exerts these effects in humans, or affects the absorption of other nutritionally important lipids or fat-soluble vitamins (A,D,E,K). Gymnema/Lab Interactions: Blood glucose, glycosylated hemoglobin (HbA1c): Based on animal research and preliminary human data, ingestion of gymnema may cause hypoglycemia in diabetic patients and reductions over time in HbA1c levels (1; 16;17;19;20;21;22;23;24;25;26). Hypoglycemic effects have been noted in patients without diabetes as well as in patients with diabetes (17). Lipid panel: In a small human study, patients with type 2 diabetes taking gymnema in addition to oral hypoglycemic drugs experienced reductions in cholesterol, triglycerides, and free fatty acids, while subjects taking oral hypoglycemic agents alone did not (1). Serum triglycerides, total cholesterol, very low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) cholesterol-lowering effects have been observed in animals (30;31). The mechanism may by via a decrease in the synthesis or increase in the metabolism of cholesterol, or through decreased fat absorption (32). Pharmacology: Constituents: Few studies have closely evaluated the constituents of Gymnema sylvestre leaf. Proposed active components include gurmarin, conduritol A, and triterpene glycosides (33;34;35). Gymnemoside b (35) gymnema acid V and VII appear to be the key saponin constituents (36). Antimicrobial effects: Gymnema was shown in one study to possess antimicrobial action against Bacillis pumilis, B. subtilis, Pseudomonas aeruginosa, and Staphylococcus aureus but not against E. coli and Proteus vulgaris (5). Hypoglycemic effects: Multiple animal studies have reported hypoglycemic effects associated with the ingestion of gymnema leaves. Gymnema reduced hyperglycemia in experimentally and spontaneously diabetic rats and rabbits (20;21;22;23;24;25;26) as well as in normal and diabetic humans (1; 5;16;17; 19;23;37;38;39;40;41;42). Gymnema may act by enhancing insulin secretion through increased pancreatic β-cell number and through improved cell function (15; 23;23). However, insulin resistance was not improved by gymnema in one animal model of diabetes (26). Other proposed mechanisms include stimulation of the release of endogenous insulin (1; 33) via interactions with insulinotropic enteric hormones, or increases in glucose utilization (21). Such activities may explain the observed hypoglycemic effects in type 2 diabetics. Gymnema has also been reported to restore levels of glycoproteins in diabetic rats to normal, thereby potentially preventing diabetic microangiopathy and other pathological organ changes (43). Lipid effects: Serum triglycerides, total cholesterol, very low-density lipoprotein (VLDL), and lowdensity lipoprotein (LDL) cholesterol-lowering effects have been observed in animals (30;31). The mechanism may by via a decrease in the synthesis or increase in the metabolism of cholesterol, or through decreased intestinal fat absorption (32). Taste effects: Gymnema has been reported to possess a sweet taste-suppressing effect, attributed to the peptide gurmarin (6;27;28). This effect may result from interference with Na+/K+ ATPase activity of taste receptors (29), or from neural inhibition (7). Historically, this phenomenon has been observed, prompting the Hindi name gurmar or "sugar destroyer." Saponin I and the sodium salt of alternoside II (4) from gymnema exhibited antisweet activity (44). Weight loss effects: Human study has investigated Gymnema sylvestre extract (GSE) 400mg in combination with other agents for weight loss; however, the exact mechanism of action involving gymnema is unclear (18). Pharmacodynamics/Kinetics: Absorption: In one small human study, it was reported that oral administration of gymnema did not have acute effects on fasting serum glucose levels (after 45 minutes) (1). Gymnema sylvestre is a woody, climbing plant native to India. The leaves are most commonly used medicinally, although the stem is also believed to possess some pharmacological action. The leaves have been used for over 2,000 years in India to treat madhu meha, or "honey urine." Chewing the leaves was noted to diminish the ability to discriminate sweet tastes, which along with hypoglycemic properties may have prompted the Hindi name gurmar, or "sugar destroyer." Gymnema has a long history of use in individuals with diabetes. Extracts of gymnema are widely used in Australian, Japanese, Vietnamese, and Indian folk medicine. Gymnema preparations modulate taste, particularly suppressing sweet taste sensations, and are used in the treatment of diabetes mellitus and in food additives against obesity and caries. Gymnema has become a popular natural product used in the management of blood sugar levels in individuals with diabetes and is believed by some to play a role in reducing serum lipids (41). Condition Study Design Author, Year N Statistically Quality of Magnitude ARR NNT Significant? Study of Benefit 0-2=poor 3-4=good 5=excellent Comments Type 1 diabetes Controlled trial, Shanmugasundaram, 64 non-randomized, 1990 non-blinded Yes 0 Large 59% 2 GS4 (gymnema) plus insulin vs. insulin alone. 11 dropouts. 40 nondiabetics also studied. Author affiliated with manufacturer. Type 2 diabetes Before and after study, nonrandomized, non-blinded Baskaran, 1990 47 Yes 1 Large 23% 4 GS4 (gymnema) added to oral hypoglycemic drugs improved fasting glucose and HbA1c levels. Type 2 diabetes Case series Kothe, 1997 21 NA 0 NA NA NA Gymnema Type 2 diabetes Case series Khare, 1983 16 Yes 0 Large NA NA 10 days of Hyperlipidemia Before and after study, nonrandomized, non-blinded Baskaran, 1990 47 Yes 1 Large NA NA Plasma lipids was Weight loss Preuss, 2004 60 Yes P P NA NA Moderately obese Randomized, double-blind, placebo controlled Type 1 diabetes mellitus administered over 6-month period. Uncontrolled. Limited reporting of numerical results. gymnema reduced serum glucose levels in both diabetic and non-diabetic patients. a secondary outcome. subjects. Study used a combination of water-soluble, calciumpotassium salt of (-)-hydroxycitric acid 4,667mg, niacin-bound chromium 4 mg and Gymnema sylvestre extract 400mg. Summary: Multiple animal studies have noted gymnema to lower serum glucose levels (5;20;20;21;22; 23;24;25;26;37;38;39;40;41;42). Preliminary evidence from small, methodologically flawed human trials suggest hypoglycemic effects of chronic oral gymnema when used in patients with type 1 or type 2 diabetes, as an adjunct to insulin or oral hypoglycemic drugs. The onset of effect has not been clearly described, although one study noted that oral administration of gymnema did not have acute effects on fasting serum glucose levels (after 45 minutes) (1). The available studies have assessed the effects of gymnema after 10 days, up to 20 months. Although it appears that gymnema may act to lower serum glucose levels, further studies of dosing, safety, and efficacy are merited before a strong recommendation can be made. Multiple drugs are available that have been demonstrated to establish good long-term control of blood glucose levels, and gymnema has not been thoroughly evaluated as a safe or effective alternative or adjunct to these agents. Evidence: Shanmugasundaram et al. conducted a study in 64 individuals with type 1 diabetes (19). All subjects were continued on insulin therapy during the trial, and 27 patients were concurrently started on 200mg twice daily of GS4 (an ethanolic acid-precipitated extract of gymnema). Outcomes measures included fasting glucose levels, glycosylated hemoglobin (HbA1c) levels, and insulin requirements. The gymnema subjects were followed for a period, which varied, from 6-30 months, while the 37 insulin-only controls were tracked for 10-12 months. Eleven subjects dropped out during the initial six months (10 for non-medical reasons, one for brittle diabetes). In the gymnema group, mean insulin requirements were reduced by 50%, accompanied by significant reductions in mean fasting blood glucose levels, from 232mg/dL to 152mg/dL. Glycosylated hemoglobin (HbA1c) levels were also reportedly reduced. The insulin-only group exhibited no significant mean decreases in insulin requirements or blood sugar levels. Subjective measures of well being (alertness, work, and school performance) were also reported to improve with gymnema therapy. A secondary outcome of C-peptide level was measured in the two groups, and compared to values for 40 non-diabetic individuals. A statistically significant lower mean Cpeptide value was found in the gymnema plus insulin group (0.185) vs. insulin alone (0.272), but was higher than the mean value in non-diabetics (0.105). During the study, no adverse effects besides hypoglycemia were observed. Although these results are promising, the lack of blinding allows for the possible introduction of bias, and the lack of randomization may allow for the influence of confounding factors. Baseline patient characteristics and statistical analysis were not well described. The principal author is involved with a company that produces a GS4 product. Type 2 diabetes mellitus Summary: Multiple animal studies have noted gymnema to lower serum glucose levels (5;20;21;22;23; 24;25;26;37;38;39;40;41;42). Preliminary evidence from small, methodologically flawed human trials suggest hypoglycemic effects of chronic oral gymnema when used in patients with type 1 or type 2 diabetes, as an adjunct to insulin or oral hypoglycemic drugs. The onset of effect has not been clearly described, although one study noted that oral administration of gymnema did not have acute effects on fasting serum glucose levels (after 45 minutes) (1). The available studies have assessed effects of gymnema after 10 days, up to 20 months. Although it appears that gymnema may act to lower serum glucose levels, further studies of dosing, safety, and efficacy are merited before a strong recommendation can be made. Multiple drugs are available that have been demonstrated to establish good long-term control of blood glucose levels, and gymnema has not been thoroughly evaluated as a safe or effective alternative or adjunct to these agents. Evidence: Baskaran et al. performed a controlled, non-randomized, non-blinded study in 47 patients with type 2 diabetes (1). GS4 extract (400mg daily) was administered for 18-20 months to 22 patients, in addition to baseline conventional oral hypoglycemic agents. The control group remained on conventional drug therapy alone without GS4, and was followed for 12 months. After 18-20 months, in the gymnema group, fasting glucose levels were reported to be 29% lower than baseline (p<0.001), and mean glycosylated hemoglobin (HbA1c) levels decreased from a baseline value of 11.91% to 8.48% (p<0.001). Insulin responses ware reported as being superior in the gymnema-supplemented group (p<0.01). Five subjects in the gymnema group were able to discontinue hypoglycemic medications. No significant changes in glucose levels or HbA1c were observed in patients continued on oral hypoglycemic medications alone after 8-10 months. As a secondary outcome, blood lipid levels were evaluated. In the GS4 group, there were significant reductions in plasma lipid levels, including cholesterol, triglycerides, and free fatty acids, while lipid levels in patients on conventional drug therapy alone remained elevated. Methodological limitations of this study include the lack of randomization or blinding. Glucose and HbA1c levels were compared to baseline values in each group, rather than compared between groups, making this a "before-and-after" study design (a methodologically weaker design than a between-group comparison). A briefly described case series by Kothe and Uppal examined the use of gymnema in 21 subjects with type 2 diabetes over a six-month period (16). This paper was presented at the Scientific Session of the 9th Annual International Homeopathic Conference of the Asian Homeopathic Medical League, Jaipur, India. All subjects received 6-15 drops of Gymnema sylvestre "Q" with 1/4 cup of water, taken 2-4 times daily, on a sliding scale based on blood sugar measurements. Additional homeopathic remedies were allowed in "complicated" cases. The authors reported that 16 of 21 patients demonstrated "moderate" to "excellent" blood glucose control. Although suggestive, the lack of a control group and vague description of baseline patient characteristics raises questions about whether these results were due to the natural course of disease, rather than a result of gymnema therapy. Details were not provided regarding methodology or data analysis, and glucose levels during the study period were provided only for two patients. Results may have been confounded by the use of additional homeopathic remedies in some patients, which were not described. In a 10-day study described in a letter to the editor, Khare et al. investigated the effects of gymnema on glucose levels in 10 healthy young adults (ages 19-25) and six diabetic adults (age 35-50) with mild-tomoderate baseline hyperglycemia, but without diagnosed diabetic complications (17). Subjects were not receiving diabetes treatment prior to the trial. Glucose tolerance tests were performed before and after administration of gymnema (2 grams, three times daily of a 10g/100mL aqueous decoction of shadedried powdered leaves). Administration of gymnema for 10 days significantly reduced fasting blood sugar levels compared to baseline in both normal and diabetic subjects, and significantly reduced mean glucose levels in diabetics after oral glucose load at both 30 minutes (110.7mg/dL vs. 135.7mg/dL) and 120 minutes (180.7mg/dL vs. 220.0mg/dL). As a case series, this study lacked comparison to controls receiving placebo or a comparison agent. Methodology and statistical analysis were not well described in this brief publication. Hyperlipidemia Summary: Reductions in levels of serum triglycerides, total cholesterol, very low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) have been observed in animals following the administration of gymnema (30;31). The mechanism may by via a decrease in the synthesis or increase in the metabolism of cholesterol, or through decreased intestinal fat absorption (32). One study of gymnema in type 2 diabetes patients reported decreased cholesterol and triglyceride levels as a secondary outcome (1). Further study is warranted in this area before an evidence-based recommendation can be made. Evidence: Baskaran et al. performed a controlled, non-randomized, unblinded study in 47 patients with type 2 diabetes (1). Gymnema extract GS4 (400mg daily) was administered for 18-20 months to 22 patients, in addition to baseline conventional oral hypoglycemic agents. The control group remained on conventional drug therapy alone without GS4, and was followed for 12 months. Although this study was designed to evaluate the effects of gymnema on serum glucose levels, the measurement of plasma lipids was a secondary outcome assessed in this study. In the GS4 group, statistically significant reductions in plasma lipid levels were observed vs. baseline, including cholesterol (18% reduction), triglycerides (16% reduction), and free fatty acids (22% reduction), while lipid levels in patients on conventional drug therapy alone remained unchanged. Methodological limitations of this study include the lack of randomization or blinding. Lipid levels appear to have been compared to baseline values in each group, rather than compared between groups, making this a "before-and-after" study design (a methodologically weaker design than a between-group comparison). Weight loss Summary: Gymnema sylvestre extract (GSE) has been shown to be effective for weight loss when used in combination with other products. The effects of gymnema alone are difficult to determine, and additional high-quality trials using gymnema as a monotherapy are needed to confirm its efficacy. Evidence: Preuss et al. conducted a randomized, double-blind, placebo controlled human study in Elluru, India for eight weeks in 60 moderately obese subjects (ages 21-50, BMI >26kg/m(2)) (45). Subjects were randomly divided into three groups. Group A was administered a water-soluble, calciumpotassium salt of (-)-hydroxycitric acid (HCA-SX) 4,667mg, group B was administered a combination of HCA-SX 4,667mg, niacin-bound chromium (NBC) 4mg and Gymnema sylvestre extract (GSE) 400mg, while group C was given placebo daily in three equally divided doses 30-60 minutes before meals. All subjects received a 2,000kcal diet daily and participated in supervised walking. At the end of eight weeks, body weight and BMI decreased by 5-6% in both groups A and B. Eighty-two subjects completed the study. No significant adverse effects were observed. Food intake, total cholesterol, lowdensity lipoproteins, triglycerides, and serum leptin levels were significantly reduced in both groups, while high-density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal or non-significant effect was observed in all parameters in group C. The present study shows that optimal doses of HCA-SX and, to a greater degree, the combination of HCA-SX, NBC, and GSE can serve as an effective and safe weight-loss formula that can facilitate a reduction in excess body weight and BMI, while promoting healthy blood lipid levels. One limitation of this study is that GSE was used in combination with other therapies. In 2005, Preuss et al. combined data from two previously reported randomized, double-blind, placebo controlled clinical studies in order to achieve a better statistical evaluation based on a larger population (18). The authors concluded that dosage levels, timing of administration, subject compliance, and bioavailability of HCA-SX significantly affect results and that when taken as directed, HCA-SX is a highly effective adjunct to healthy weight control. However, these results also do not directly evaluate gymnema. Brands used in statistically significant clinical trials: Proβeta® (PharmaTerra, Inc; Bellevue, WA): A patented ethanolic acid-precipitated extract from gymnema, also called GS4. According to the makers of Proβeta®, the preparation is standardized to possess a specific biological result, as measured by a test developed by the company, which evaluates "pancreotropic®" effects (1;19;23). Brands shown to contain claimed ingredients through third-party testing: Consumer Lab: NA. Last accessed 7/24/08. Consumer Reports: NA. Last accessed 7/24/08. Natural Products Association: NA. Last accessed 7/24/08. NSF International: NA. Last accessed 7/24/08. US Pharmacopeia: NA. Last accessed 7/24/08. Other: Beta Fast GXR (Informulab): 400mg standardized to 25% gymnemic acids; Gymnesyl (Nature's Herbs): Extract standardized for 150mg of crude gymnemic acids; Gymnema (Nature's Way): 260mg standardized to 75% gymnemic acids. Authors/Editors: Tracee Rae Abrams, PharmD (University of Rhode Island); Ethan Basch, MD (Natural Standard research Collaboration); Theresa Davies-Heerema, PhD (Boston School of Medicine); Ivo Foppa, MD, ScD (University of South Carolina); Paul Hammerness, MD (Harvard Medical School); Erica Seamon, PharmD (Natural Standard Research Collaboration); Shaina Tanguay-Colucci, BS (Natural Standard Research Collaboration); Sarah Taylor, PharmD (University of Pittsburgh); Catherine Ulbricht, PharmD, MBA[c] (Massachusetts General Hospital); Minney Varghese, BS (Northeastern University); Wendy Weissner, BA (Natural Standard Research Collaboration); Jen Woods, BS (Natural Standard Research Collaboration). Blinded Peer Review: Natural Standard Editorial Board. 1. Baskaran, K, Ahamath, BK, Shanmugasundaram, KR, and et all. Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J Ethnopharm 1990;30:295-305. 2. Cicero, A. F., Derosa, G., and Gaddi, A. What do herbalists suggest to diabetic patients in order to improve glycemic control? Evaluation of scientific evidence and potential risks. Acta Diabetol. 2004;41(3):91-98. View Abstract 3. Grover, J. K., Yadav, S., and Vats, V. Medicinal plants of India with anti-diabetic potential. J Ethnopharmacol. 2002;81(1):81-100. View Abstract 4. Shapiro, K. and Gong, W. C. Natural products used for diabetes. J Am Pharm Assoc (Wash.) 2002;42(2):217-226. View Abstract 5. Satdive, R. K., Abhilash, P., and Fulzele, D. P. Antimicrobial activity of Gymnema sylvestre leaf extract. Fitoterapia 2003;74(7-8):699-701. View Abstract 6. Brala, P and Hagen, R. 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