Effect of Gymnema Sylvestre on Metabolic Syndrome and Insulin

• ClinicalTrials.gov Identifier: NCT02370121
• Recruitment Status: Completed
• First Posted: February 24, 2015
• Results First Posted: June 3, 2016
• Last Update Posted: June 18, 2019
• Sponsor: University of Guadalajara
• Information provided by (Responsible Party): Esperanza Martínez-Abundis, University of Guadalajara

Study Description

Brief Summary:

Gymnema sylvestre has demonstrated promising effects in the treatment of obesity, dyslipidemia, hypertension, insulin secretion, among others. The above mentioned findings show that Gymnema sylvestre has an excellent potential for the prevention and treatment of metabolic syndrome.

Condition or disease	Intervention/treatment	Phase
Metabolic Syndrome	Drug: Placebo; Drug: Gymnema Sylvestre	Phase 2

Detailed Description:

A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients with a diagnosis of metabolic syndrome in accordance with the modify International Diabetes Federation criteria. The patients received 300 mg capsules of Gymnema sylvestre or placebo, two times daily before breakfast and dinner for 90 days. Before and after intervention the investigators evaluated: The components of metabolic syndrome (waist circumference, triglycerides, high-density lipoprotein, fasting glucose and blood pressure), body weight, body mass index, total cholesterol, low-density lipoprotein, very-low-density lipoprotein, creatinine, aspartate transaminase and alanine transaminase.

Were calculated: Areas under the curve of glucose and insulin were calculated with de Trapezoidal formula. Total insulin secretion was evaluated with the Insulinogenic index and the insulin sensitivity was estimated using the Matsuda index.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Gymnema Sylvestre Administration on Metabolic Syndrome, Insulin Sensitivity and Insulin Secretion
• Study Start Date: February 2013
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: January 2015

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; 600 mg dose per day. Two capsules of 300 mg, one in the morning with the first meal and the other at dinner during 90 days.	Drug: Placebo; Capsules of 300 mg two times per day before breakfast and dinner a total dose of 600 mg per day. During 90 days.; Other Name: Calcined Magnesia
Experimental: Gymnema Sylvestre; 600 mg dose per day. Two capsules of 300 mg, one in the morning with the first meal and the other at dinner during 90 days.	Drug: Gymnema Sylvestre; Capsules of 300 mg of calcined magnesium two times per day before breakfast and dinner a total dose of 600 mg per day. During 90 days.; Other Name: Gurmar

Outcome Measures

Primary Outcome Measures :

1. Waist Circumference (WC) [ Time Frame: Week 12 ]
   The WC was evaluated after an overnight fast with a flexible tape in the midpoint between the lowest rib and the iliac crest and is expressed in centimeters.
2. Triglycerides (TGs) [ Time Frame: week 12 ]
   The blood sample for determining of TGs, was taken after an overnight fast and was evaluated by spectrophotometry method. The value was expressed on mmol/L.
3. High-density Lipoprotein Cholesterol (HDL-C) [ Time Frame: Week 12 ]
   The blood sample for determining of HDL-C, was taken after an overnight fast and was evaluated by colorimetric method. The value was expressed on mmol/L.
4. Fasting Plasma Glucose (FPG) [ Time Frame: week 12 ]
   The blood sample for determining of FPG, was taken after an overnight fast and was evaluated by spectrophotometry method. The value was expressed on mmol/L.
5. Systolic Blood Pressure (SBP) [ Time Frame: week 12 ]
   The SBP was evaluated with a digital sphygmomanometer with the subject sited down on a chair after a resting period of 5 minutes on three occasions. The mean of the three measures was considered as the value of SBP. The value was expressed on mmHg.
6. Diastolic Blood Pressure (DBP) [ Time Frame: week 12 ]
   The DBP was evaluated with a digital sphygmomanometer with the subject sited down on a chair after a resting period of 5 minutes on three occasions. The mean of the three measures was considered as the value of DBP. The value was expressed on mmHg.
7. Total Insulin Secretion [ Time Frame: Week 12 ]
   The total insulin secretion was calculated by the insulinogenic index (ΔABC insulin / ΔABC glucose).
8. First Phase of Insulin Secretion [ Time Frame: week 12 ]
   The first phase of insulin secretion was estimated using the Stumvoll index (1283+ 1.829 x insulin 30' - 138.7 x glucose 30' + 3.772 x insulin 0').
9. Insulin Sensitivity [ Time Frame: week 12 ]
   The insulin sensitivity was calculated with Matsuda index [10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)].

Secondary Outcome Measures :

1. Body Weight (BW) [ Time Frame: week 12 ]
   The BW was evaluated after an overnight fast, through a bioimpedance digital scale results are reported in kilograms with a decimal.
2. Body Mass Index (BMI) [ Time Frame: week 12 ]
   The BMI was calculated by the square of the body height, and is universally expressed in units of kg/m2, resulting from mass in kilograms and height in metres.
3. Total Cholesterol (TC) [ Time Frame: week 12 ]
   The blood sample for determining of TC, was taken after an overnight fast and was evaluated by spectrophotometry method. The value was expressed on mmol/L.
4. Low-density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Week 12 ]
   The blood sample for determining of LDL-C, was taken after an overnight fast and was calculated by Friedewald formula. The value was expressed on mmol/L.
5. Very-low Density Lipoprotein (VLDL) [ Time Frame: week 12 ]
   The blood sample for determining the VLDL, was taken after an overnight fast and was calculated as triglycerides/5. The value was expressed on mmol/L.
6. 2-hour Postload Plasma Glucose (2-h PG) [ Time Frame: week 12 ]
   The blood sample for determining of 2-h PG, was taken two hours after the ingestion of the drink with 75 g dextrose and was evaluated by spectrophotometry method. The value was expressed on mmol/L.
7. Area Under the Curve of Glucose (AUCG) [ Time Frame: week 12 ]
   The estimation for AUCG was calculated from parameters obtained during the 2 hours oral glucose tolerant test (OGTT) with 75 g dextrose by trapezoidal integration. The value was expressed mmol/L/min.
8. Area Under the Curve of Insulin (AUCI) [ Time Frame: week 12 ]
   The estimation for AUCI was calculated from parameters obtained during the 2 hours oral glucose tolerant test (OGTT) with 75 g dextrose by trapezoidal integration. The value was expressed on pmol/L/min.

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Letter of consent and release signed by each patient
• Body mass index: 25-34.99 kg/m2
• Body weight without variations above or under 5% during the three months prior to the study
• Diagnostic of metabolic syndrome according to the modified International Diabetes Federation definition: Central obesity (defined as waist circumference ≥ 80 cm in women and ≥ 90 cm in men)

Plus any two of the following four factors:

• Triglycerides: 150-499 mg/dL.
• High density lipoprotein: Woman < 50 mg/dL, man < 40 mg/dL.
• Blood pressure systolic:130-139 mmHg and/or Blood pressure diastolic: 85-89 mmHg
• Fasting glucose: 100-125 mg/dL

Exclusion Criteria:

• Type 1 or 2 diabetes mellitus
• Previous pharmacological treatment for components of metabolic syndrome
• Mental or physical illness interfering with the study
• Thyroid or cardiovascular disease
• Pregnant or suspected pregnant women
• Woman breastfeeding
• Index of body mass: ≥ 35 kg/m2
• Treatments known to affect metabolism of glucose, fats and affecting arterial tension
• Patients with hepatic or renal diseases background
• Patients diagnosed with kidneys disease
• Calcined magnesium intolerance
• Gymnema Sylvestre intolerance

Contacts and Locations

Sponsors and Collaborators

University of Guadalajara

Investigators

• Principal Investigator: Esperanza Martínez, PhD; Institute of Experimental and Clinical Therapeutics

More Information

Publications of Results:

Al-Romaiyan A, Liu B, Asare-Anane H, Maity CR, Chatterjee SK, Koley N, Biswas T, Chatterji AK, Huang GC, Amiel SA, Persaud SJ, Jones PM. A novel Gymnema sylvestre extract stimulates insulin secretion from human islets in vivo and in vitro. Phytother Res. 2010 Sep;24(9):1370-6. doi: 10.1002/ptr.3125.

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 Jun;24(6):713-7. doi: 10.1248/bpb.24.713.

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 Oct;30(3):295-300. doi: 10.1016/0378-8741(90)90108-6.

Porchezhian E, Dobriyal RM. An overview on the advances of Gymnema sylvestre: chemistry, pharmacology and patents. Pharmazie. 2003 Jan;58(1):5-12.

Koshu K, Hirota S, Sonobe M, Takahashi S, Takaku A, Saito T, Ushijima T. [Continuous recording of cerebral blood flow by means of thermal diffusion method using Peltier stack]. Neurol Med Chir (Tokyo). 1987 Aug;27(8):724-8. doi: 10.2176/nmc.27.724. No abstract available. Japanese.

Bhansali S, Shafiq N, Pandhi P, Singh AP, Singh I, Singh PK, Sharma S, Malhotra S. Effect of a deacyl gymnemic acid on glucose homeostasis & metabolic parameters in a rat model of metabolic syndrome. Indian J Med Res. 2013 Jun;137(6):1174-9.

Tiwari P, Mishra BN, Sangwan NS. Phytochemical and pharmacological properties of Gymnema sylvestre: an important medicinal plant. Biomed Res Int. 2014;2014:830285. doi: 10.1155/2014/830285. Epub 2014 Jan 6.

Kumar V, Bhandari U, Tripathi CD, Khanna G. Protective Effect of Gymnema sylvestre Ethanol Extract on High Fat Diet-induced Obese Diabetic Wistar Rats. Indian J Pharm Sci. 2014 Jul;76(4):315-22.

Astell KJ, Mathai ML, Su XQ. Plant extracts with appetite suppressing properties for body weight control: a systematic review of double blind randomized controlled clinical trials. Complement Ther Med. 2013 Aug;21(4):407-16. doi: 10.1016/j.ctim.2013.05.007. Epub 2013 Jun 24.

Al-Romaiyan A, King AJ, Persaud SJ, Jones PM. A novel extract of Gymnema sylvestre improves glucose tolerance in vivo and stimulates insulin secretion and synthesis in vitro. Phytother Res. 2013 Jul;27(7):1006-11. doi: 10.1002/ptr.4815. Epub 2012 Aug 21.

Ogawa Y, Sekita K, Umemura T, Saito M, Ono A, Kawasaki Y, Uchida O, Matsushima Y, Inoue T, Kanno J. [Gymnema sylvestre leaf extract: a 52-week dietary toxicity study in Wistar rats]. Shokuhin Eiseigaku Zasshi. 2004 Feb;45(1):8-18. doi: 10.3358/shokueishi.45.8. Japanese.

Okabayashi Y, Tani S, Fujisawa T, Koide M, Hasegawa H, Nakamura T, Fujii M, Otsuki M. Effect of Gymnema sylvestre, R.Br. on glucose homeostasis in rats. Diabetes Res Clin Pract. 1990 May-Jun;9(2):143-8. doi: 10.1016/0168-8227(90)90106-4.

Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999 Sep;22(9):1462-70. doi: 10.2337/diacare.22.9.1462.

Tai MM. A mathematical model for the determination of total area under glucose tolerance and other metabolic curves. Diabetes Care. 1994 Feb;17(2):152-4. doi: 10.2337/diacare.17.2.152.

Renga B, Festa C, De Marino S, Di Micco S, D'Auria MV, Bifulco G, Fiorucci S, Zampella A. Molecular decodification of gymnemic acids from Gymnema sylvestre. Discovery of a new class of liver X receptor antagonists. Steroids. 2015 Apr;96:121-31. doi: 10.1016/j.steroids.2015.01.024. Epub 2015 Feb 7.

Stumvoll M, Mitrakou A, Pimenta W, Jenssen T, Yki-Jarvinen H, Van Haeften T, Renn W, Gerich J. Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care. 2000 Mar;23(3):295-301. doi: 10.2337/diacare.23.3.295.

Izutani Y, Murai T, Imoto T, Ohnishi M, Oda M, Ishijima S. Gymnemic acids inhibit rabbit glyceraldehyde-3-phosphate dehydrogenase and induce a smearing of its electrophoretic band and dephosphorylation. FEBS Lett. 2005 Aug 15;579(20):4333-6. doi: 10.1016/j.febslet.2005.06.070.

Wang Y, Dawid C, Kottra G, Daniel H, Hofmann T. Gymnemic acids inhibit sodium-dependent glucose transporter 1. J Agric Food Chem. 2014 Jun 25;62(25):5925-31. doi: 10.1021/jf501766u. Epub 2014 Jun 10.

Other Publications:

Lann D, LeRoith D. Insulin resistance as the underlying cause for the metabolic syndrome. Med Clin North Am. 2007 Nov;91(6):1063-77, viii. doi: 10.1016/j.mcna.2007.06.012.

Abdul-Ghani MA, Matsuda M, Balas B, DeFronzo RA. Muscle and liver insulin resistance indexes derived from the oral glucose tolerance test. Diabetes Care. 2007 Jan;30(1):89-94. doi: 10.2337/dc06-1519.

Sandeep S, Gokulakrishnan K, Velmurugan K, Deepa M, Mohan V. Visceral & subcutaneous abdominal fat in relation to insulin resistance & metabolic syndrome in non-diabetic south Indians. Indian J Med Res. 2010 May;131:629-35.

• Responsible Party: Esperanza Martínez-Abundis, Researcher Professor, University of Guadalajara
• ClinicalTrials.gov Identifier: NCT02370121
• Other Study ID Numbers: CT-271281-YZ
• First Posted: February 24, 2015
• Results First Posted: June 3, 2016
• Last Update Posted: June 18, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Esperanza Martínez-Abundis, University of Guadalajara:

Gymnema Sylvestre; Insulin Secretion; Insulin Sensitivity; Central Obesity

Additional relevant MeSH terms:

Metabolic Syndrome; Syndrome; Disease; Pathologic Processes; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases