The effect of Irvingia gabonensis seeds on body weight and
Transcription
The effect of Irvingia gabonensis seeds on body weight and
Lipids in Health and Disease BioMed Central Open Access Research The effect of Irvingia gabonensis seeds on body weight and blood lipids of obese subjects in Cameroon Judith L Ngondi, Julius E Oben* and Samuel R Minka Address: Nutrition, HIV and Health Research Unit, Department of Biochemistry, P.O Box 812, Faculty of Science, University of Yaounde I, Cameroon Email: Judith L Ngondi - jngondi@yahoo.com; Julius E Oben* - juliusoben@hotmail.com; Samuel R Minka - sminka@uycdc.uninet.cm * Corresponding author Published: 25 May 2005 Lipids in Health and Disease 2005, 4:12 doi:10.1186/1476-511X-4-12 Received: 26 February 2005 Accepted: 25 May 2005 This article is available from: http://www.lipidworld.com/content/4/1/12 © 2005 Ngondi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Dietary fibres are frequently used for the treatment of obesity. The aim of this study was to evaluate the efficacy of Irvingia gabonensis seeds in the management of obesity. This was carried out as a double blind randomised study involving 40 subjects (mean age 42.4 years). Twenty-eight subjects received Irvingia gabonensis (IG) (1.05 g three time a day for one month) while 12 were on placebo (P) and the same schedule. During the one-month study period all subjects were on a normocaloric diet evaluated every week by a dietetic record book. At the end, the mean body weight of the IG group was decreased by 5.26 ± 2.37% (p < 0.0001) and that of the placebo group by 1.32 ± 0.41% (p < 0.02). The difference observed between the IG and the placebo groups was significant (p < 0.01). The obese patients under Irvingia gabonensis treatment also had a significant decrease of total cholesterol, LDL-cholesterol, triglycerides, and an increase of HDL-cholesterol. On the other hand, the placebo group did not manifest any changes in blood lipid components. Irvingia gabonensis seed may find application in weight lose. Introduction Obesity is of major primary care concern and is targeted as an international health objective in Healthy 2000, which seeks to reduce the prevalence of obesity to less than 20%. In the last 10 years, the number of overweight people has increased from 26 to 34% [1]. Conventional dietary and behavioral treatment have failed in long-term management. Dietary strategies used to manage obesity include the use of high fibre, low carbohydrates and fats diet [2,3]. Beneficial effect of dietary fibre in the management of obesity is not well established, since their mechanism of action is not known. The discovery of new medicinal plants has led to the creation of potential drugs that modify feeding behavior and metabolism and may therefore have application in weight management. The aim of the present study is to investigate the effect of Irvingia gabonensis extract on body weight. Subjects and methods A total of 40 obese subjects aged between 19 and 55 years were selected from a group responding to a radio advertisement. After physical examination and laboratory screening tests, diabetics, pregnant and lactating women were excluded. None of these subjects took any weight reducing medication and none was following any specific diet. The purpose, nature and potential risks of the study were explained to all patients and a written informed consent was obtained before their participation. The local research ethics committee approved the experimental protocol. Page 1 of 4 (page number not for citation purposes) Lipids in Health and Disease 2005, 4:12 http://www.lipidworld.com/content/4/1/12 Table 1: Effect of Irvingia gabonensis crude extract on body weight, body fat, waist and hip circumferences Treatment period (weeks) Weight (kg Active Placebo Active Placebo Active Placebo Active Placebo Body fat (%) Waist (cm) Hip (cm) 0 2 4 105.10 ± 16.98 79.43 ± 9.83 46.11 ± 4.4848 40.58 ± 3.49 112.76 ± 20.5 81.1 ± 7.1 125.69 ± 11.34 122.2 ± 10.7 102.3 ± 17.06 79.43 ± 9.83 46.5 ± 3.68 40.58 ± 3.9 109.7 ± 20.4 81,91 ± 7,91 122.92 ± 10.67 122.2 ± 10.7 101.01 ± 16.63 79.33 ± 10.63 45.34 ± 3.52 40.3 ± 3.8 106.6 ± 20.79 81.25 ± 7.52 121.15 ± 10.39 121.5 ± 10.9 Table 2: Effect Irvingia gabonensis on systolic (SBP) and diastolic (DBP) blood pressure Treatment period (weeks) 0 SBP (mmHg) Active Placebo Active placebo DBP (mmHg) 2 136.41 ± 19.57 134 ± 5.05 98.5 ± 19.52 93.50 ± 10.31 4 132.66 ± 18.48* 121.5 ± 5.89 97.5 ± 22.80 93.83 ± 7.41 132.83 ± 17.97* 123.83 ± 2.92 94.08 ± 11.07 91.5 ± 6.53 Values are means ± sem. Significant differences were at *P < 0.001 by comparison to the placebo group. Table 3: The effect of Irvingia gabonensis on blood total cholesterol (TC), triglyceride (TRI), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c) and glucose. Active Placebo Initial Final Initial Final T-cholesterol TRI HDL-c LDL-c LDL/HDL T-cho/HDL GLUCOSE 215 ± 55.12 130.68 ± 39.5 163.70 ± 25.32 158.36 ± 30.46 162 ± 33.15 89.22 ± 55.63 130.65 ± 37.82 100.52 ± 32.55 61.23 ± 20.36 89.9 ± 28.44 31.38 ± 25.21 121.37 ± 36.3 66.08 ± 34.27 105.06 ± 11.86 98.55 ± 27.99 1.98 ± 1.78 0.735 ± 1.20 5.05 ± 3.94 3.51 ± 2.70 1.45 ± 1.38 6.44 ± 3.37 3.8 ± 1.92 2.57 ± 1.03 3.6 ± 0.41 3.19 ± 1.85 4.51 ± 2.07 3.9 ± 0.74 41.20 ± 19.53 Study design The study was as a randomised, double blind placebocontrolled crossover design, and consisted of a 4-week treatment period. Subjects were given two different types of capsules containing 350 mg of Irvingia gabonensis seed extract (active formulation) or oat bran (placebo). Three capsules were taken three times daily, one-half hour before meals (a total daily amount of 3.15 g of Irvingia gabonensis seed extract) with a glass of warm water. Capsules were identical in shape, colour and appearance, with neither patients nor researchers knowing what capsule they received. During the experimental period, subjects were examined weekly, with their body weight, body fat, waist and hip circumferences recorded each time. Subjective findings such as increased or decreased appetite, feeling of lightness and gastrointestinal pains were individually noted. Side effects of the active extract, if any were also solicited and noted during each visit. The subjects were also interviewed about their physical activity and food intake during the trial, and were instructed to eat a low fat diet (1800 Kcal) as well as keep a record for seven consecutive days (using household measurements). Page 2 of 4 (page number not for citation purposes) Lipids in Health and Disease 2005, 4:12 Anthropometric measurements Anthropometric measurements were done at each visit, with body weight and body fat (impedance measurement using a TANITA™ monitor Scale) measurements on fasted (12 hour) subjects wearing light clothing. Waist and hip circumferences were measured by soft non-stretchable plastic tape on the narrowest and the widest parts of the trunk. Laboratory methods Blood samples were collected after a 12 h overnight fast into heparinized tubes at the beginning of the study, after two weeks and at the end (4 weeks) of treatment. The concentrations of total cholesterol, triacylglycerol, HDL-cholesterol, and glucose, in plasma were measured using a commercial diagnostic kit (Cholesterol infinity, triglycerides Int, EZ HDL™ cholesterol, EZ LDL™ cholesterol, Glucose Trinder, respectively) from SIGMA Diagnostics Statistical Analysis Results are expressed as mean ± SEM except for anthropometric measurements. Paired Student's t-test was carried out on the start and end values of placebo and Irvingia gabonensis capsules and also on the differences between the placebo and Irvingia gabonensis crude extract. Results Effect on body composition Irvingia gabonensis induced a decrease in weight of 2.91 ± 1.48% (p < 0.0001) after two weeks and 5.6 ± 2.7% (p < 0,0001) after one month. Although the percentage of body fat was not significantly reduced with both placebo and IG, the waist circumference (5.07 ± 3.18%; p < 0.0001) and hip circumference (3.42 ± 2.12%; p < 0,0001) were significantly reduced by IG. A reduction of 1.32 ± 0.41% (p < 0.02) and 2.23 ± 1.05% (p < 0.05) was observed with the placebo after two and four weeks respectively of treatment. Effect on blood pressure From the second week of experimentation, the systolic blood pressure was significantly reduced by the active extract (Table 2). http://www.lipidworld.com/content/4/1/12 Discussion The soluble fibre of the seed of Irvingia gabonensis like other forms of water-soluble dietary fibres, are "bulkforming" laxatives. Irvingia gabonensis seeds delay stomach emptying, leading to a more gradual absorption of dietary sugar. This effect can reduce the elevation of blood sugar levels that is typical after a meal [4]. Controlled studies have found that after-meal blood sugar levels are lower in people with diabetes given glucomannan in their food [5] and overall diabetic control is improved with soluble fibre-enriched diets according to preliminary [6] and controlled [7,8] trials. One double-blind study reported that glucomannan (8–13 grams per day) stabilized blood sugar levels in people with the insulin resistance syndrome [9]. Like other soluble fibers, Irvingia gabonensis seed fibre can bind to bile acids in the gut and carry them out of the body in the faeces, which requires the body to convert more cholesterol into bile acids [10]. This can result in the lowering of blood cholesterol as well as other blood lipids. Controlled double-blind [11,12] studies have shown that supplementation with several grams per day of soluble fibre significantly reduced total blood cholesterol, LDL cholesterol, and triglycerides and in some cases raised HDL cholesterol, these being comparable with effects noticed with Irvingia gabonensis. Considering the wide use of Irvingia gabonensis in the preparation of various dishes in Cameroon, its use should be further encouraged for the purposes of control of dietary lipids as well as for weight reduction. References 1. 2. 3. 4. 5. Effect on blood lipids components The plasma total cholesterol cencentration was reduced by 39.21%, triglyerides by 44.9% (p < 0,05) and LDL by 45.58%. This was accompanied by a significant increase in HDL-cholesterol of 46.852%. The CT/HDL ratio (p < 0.05) and the blood glucose level were also reduced (32.36%; p < 0.05). No significant change was observed in the placebo group. 6. 7. 8. 9. 10. Bray GA: Complications of obesity. Ann Int Med 1985, 103:1052-1062. Harris MI: Epidemiological correlates of NIDDM in Hispanics, whites, and blacks in the U.S. population. Diabetes Care 1991, 14(suppl 3):639-648. Weintraub M: Long-term weight control study: conclusions. Clinic Pharmacol Ther 1992:581. Passaretti S, Franzoni M, Comin U, et al. Action of glucomannans on complaints in patients affected with chronic constipation: a multicentric clinical evaluation. Ital J Gastroenterol 1991;23:421-5 Vuksan V, Jenkins DJ, Spadafora P, et al.: Konjac-mannan (glucomannan) improves glycemia and other associated risk factors for coronary heart disease in type 2 diabetes. A randomized controlled metabolic trial. Diabetes Care 1999, 22:913-9. Cesa F, Mariani S, Fava A, et al.: The use of vegetable fibers in the treatment of pregnancy diabetes and/or excessive weight gain during pregnancy. Minerva Ginecol 1990, 42:271-4. [in Italian] Vorster HH, Lotter AP, Odendaal I, et al.: Benefits from supplementation of the current recommended diabetic diet with gel fibre. Int Clin Nutr Rev 1988, 8:140-6. Hopman WP, Houben PG, Speth PA, Lamers CB: Glucomannan prevents postprandial hypoglycaemia in patients with previous gastric surgery. Gut 1988, 29:930-4. Doi K: Effect of konjac fibre (glucomannan) on glucose and lipids. Eur J Clin Nutr 1995, 49(Suppl 3):S190-7. [review] Wu J, Peng SS: Comparison of hypolipidemic effect of refined konjac meal with several common dietary fibers and their mechanisms of action. Biomed Environ Sci 1997, 10:27-37. Arvill A, Bodin L: Effect of short-term ingestion of konjac glucomannan on serum cholesterol in healthy men. Am J Clin Nutr 1995, 61:585-9. Page 3 of 4 (page number not for citation purposes) Lipids in Health and Disease 2005, 4:12 11. 12. http://www.lipidworld.com/content/4/1/12 Walsh DE, Yaghoubian V, Behforooz A: Effect of glucomannan on obese patients: a clinical study. Int J Obes 1984, 8:289-93. Vido L, Facchin P, Antonello I, et al.: Childhood obesity treatment: double blinded trial on dietary fibres (glucomannan) versus placebo. Padiatr Padol 1993, 28:133-6. Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime." Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 4 of 4 (page number not for citation purposes) Lipids in Health and Disease BioMed Central Open Access Research IGOB131, a novel seed extract of the West African plant Irvingia gabonensis, significantly reduces body weight and improves metabolic parameters in overweight humans in a randomized double-blind placebo controlled investigation Judith L Ngondi1, Blanche C Etoundi1, Christine B Nyangono1, Carl MF Mbofung2 and Julius E Oben*1 Address: 1Laboratory of Nutrition and Nutritional Biochemistry, Faculty of Science, University of Yaounde I, Yaounde, Cameroon and 2Department of Food Science and Nutrition, ENSAI, University of Ngaoundere, BP 686 Ngaoundere, Cameroon Email: Judith L Ngondi - jlngondi@yahoo.com; Blanche C Etoundi - blancuca@yahoo.fr; Christine B Nyangono - spfernande@yahoo.fr; Carl MF Mbofung - cmbofung@yahoo.com; Julius E Oben* - juliusoben@hotmail.com * Corresponding author Published: 2 March 2009 Lipids in Health and Disease 2009, 8:7 doi:10.1186/1476-511X-8-7 Received: 7 January 2009 Accepted: 2 March 2009 This article is available from: http://www.lipidworld.com/content/8/1/7 © 2009 Ngondi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: A recent in vitro study indicates that IGOB131, a novel seed extract of the traditional West African food plant Irvingia gabonensis, favorably impacts adipogenesis through a variety of critical metabolic pathways including PPAR gamma, leptin, adiponectin, and glycerol-3 phosphate dehydrogenase. This study was therefore aimed at evaluating the effects of IGOB131, an extract of Irvingia gabonensis, on body weight and associated metabolic parameters in overweight human volunteers. Methods: The study participants comprised of 102 healthy, overweight and/or obese volunteers (defined as BMI > 25 kg/m2) randomly divided into two groups. The groups received on a daily basis, either 150 mg of IGOB131 or matching placebo in a double blinded fashion, 30–60 minutes before lunch and dinner. At baseline, 4, 8 and 10 weeks of the study, subjects were evaluated for changes in anthropometrics and metabolic parameters to include fasting lipids, blood glucose, C-reactive protein, adiponectin, and leptin. Results: Significant improvements in body weight, body fat, and waist circumference as well as plasma total cholesterol, LDL cholesterol, blood glucose, C-reactive protein, adiponectin and leptin levels were observed in the IGOB131 group compared with the placebo group. Conclusion: Irvingia gabonensis administered 150 mg twice daily before meals to overweight and/or obese human volunteers favorably impacts body weight and a variety of parameters characteristic of the metabolic syndrome. This is the first double blind randomized placebo controlled clinical trial regarding the anti-obesity and lipid profile modulating effects of an Irvingia gabonensis extract. The positive clinical results, together with our previously published mechanisms of gene expression modulation related to key metabolic pathways in lipid metabolism, provide impetus for much larger clinical studies. Irvingia gabonensis extract may prove to be a useful tool in dealing with the emerging global epidemics of obesity, hyperlipidemia, insulin resistance, and their co-morbid conditions. Trial registration: ClinicalTrials.gov NCT00645775 Page 1 of 7 (page number not for citation purposes) Lipids in Health and Disease 2009, 8:7 Background Excess adipose tissue increases the workload of the cardiovascular system, adversely alters immune function, and dramatically increases the risk of heart disease, non-insulin-dependent diabetes mellitus, obstructive pulmonary disease, arthritis and a variety of cancers [1]. Although once considered a major health problem isolated to developed countries, obesity is now recognized as a global problem with potentially catastrophic consequences for health economics. In Cameroon, for example, the reported incidence of obesity in urban areas ranges from 17–21% [2]. This dramatic change reflects the social, nutritional, and lifestyle changes involved in rural-urban migration and the urbanization of rural areas. Worthy of note in this context are the changes from traditional high fibre diets and high-activity lifestyles to diets rich in saturated fat and low in fibre, further compounded by reduction in physical activity levels [3,4]. Insulin resistance, caused by the concomitant, complex interaction of environment (e.g. diet, activity level, elevated body mass, excess visceral adiposity) and genetic factors, is a fundamental pathophysiologic cause of the metabolic syndrome, a recognized risk factor for cardiovascular disease [5,6]. Like many other obesity-related conditions, the incidence of the metabolic syndrome is also on the rise in Cameroon [7]. Nutritional management, especially caloric restriction for the purpose of weight reduction, can improve insulin action on target tissues like skeletal muscle, hepatocytes, and peripheral and visceral adipocytes [8,9]. The consumption of Irvingia gabonensis, a fleshy West African fruit, is common in traditional Nigerian and Cameroonian cuisine. Initial observations suggested beneficial changes in metabolic parameters were associated with the high fiber content of Irvingia gabonensis [10]. Results of subsequent analysis suggested that the earlier observations of the beneficial effects of Irvingia gabonensis could not be accounted for by fiber content alone [11]. A recent in vitro study using a validated experimental model (murine 3T3-L1 adipocytes) provides compelling data that Irvingia gabonensis seed extract may inhibit adipogenesis through modulation of PPAR gamma and glycerol-3 phosphate dehydrogenase in addition to beneficial impact upon leptin and adiponectin [12]. The current clinical study was designed to evaluate if the in vitro data could translate into in vivo clinical efficacy in overweight and/or obese human volunteers. Participants and methods Study population Participants for the study were recruited from the city of Yaoundé, Cameroon and surrounding metro region http://www.lipidworld.com/content/8/1/7 through radio and print media advertisement. Inclusion criteria for study participation mandated: (1) men and women ages 19 to 50 years, in general good health free from significant medical illness that, in the opinion of the investigator, could adversely compromise study participation for any reason; (2) stable body weight (+/- 2 kg) for at least three months prior to study randomization without use of medication known or suspected to affect body weight or appetite; (3) no concomitant or recent (within the past three months) bacterial or seasonal viral infection (e.g. influenza); (4) BMI between 26 kg/m2 and 40 kg/m2; (5) no attempts at weight loss through dietary intervention over the three months prior to trial randomization; (6) no participation in a structured weight control program for at least three months prior to study randomization; (7) non-smoker; (8) non-drinkers of sugary fizzy drinks; (9) capability and willingness for multiple blood sampling procedures; and (10) ability to competently understand and sign the consent form. Based on the above criteria, 120 consenting volunteers (62 males and 58 females) were selected to participate in the study. The protocol used was approved by the Cameroon National Ethics Committee; the study was conducted in accord with the Helsinki Declaration (1983 version). Study design/intervention The study was a randomized, double-blind, placebo-controlled design for 10 weeks. The volunteers were randomly divided into two groups – placebo or IGOB131. The participants consumed either one capsule of placebo or one capsule of IGOB131 (containing 150 mg of Irvingia gabonensis extract) 30–60 minutes before lunch and dinner (BID) throughout the study period. Test materials All test materials were supplied by Gateway Health Alliances, Inc. (Fairfield, CA, USA) in individual packets of capsules. The identical-looking placebo and active formulation capsules contained, respectively, maize-based powder consisting of 150 mg maltodextrin, or 150 mg IGOB131. Anthropometric measurements Height was measured with a locally manufactured wallmounted stadiometer, which was calibrated against the Cameroon's Department of National Security identification scale. Body weight and percent body fat, were assessed using a Tanita™ BC-418 Segmental Body Composition Analyzer/Scale that uses bio-electrical impedance analysis for body composition analysis. Body mass index (BMI) was calculated using the weight and height measurements. Waist circumference measurements to the nearest 0.1 cm were taken at the mid-point between the Page 2 of 7 (page number not for citation purposes) Lipids in Health and Disease 2009, 8:7 bottom rib and the hip bone, without restrictive garments using a flexible non expandable tape measure. Dietary Intake Three days before the collection of baseline measurements and three times during the trial, dietary intake of subjects was evaluated by a qualified dietician. Energy and protein intakes were calculated using standard food composition tables based upon the 3-day food intake record. No major dietary intervention or formal physical activity program was instituted during the course of the study; participants were instructed to maintain the current level of physical activity prior to study randomization during the course of the study. Sample collection Fasting blood samples (5 ml of blood) were collected at baseline, and at 4, 8, and 10 weeks. Serum obtained from each blood sample was split into multiple 500 μl aliquots and stored at -20°C until needed for the measurement of total cholesterol, LDL cholesterol, fasting blood glucose, C-reactive protein, adiponectin, and leptin levels. Analytical methods Determination of glucose in blood using glucose oxidase with an alternative oxygen receptor was adopted for this study [13]. Serum total cholesterol was assayed by the cholesterol oxidase method [14] while triglycerides as well as serum glucose levels were assayed following the method described by Buccolo & David [15]. Quantitative determinations of C-reactive protein (CRP) was assessed using a high sensitivity immunoassay (Oxis International, Foster City, CA. USA) while serum leptin was determined in duplicate using an enzyme-linked immunosorbent assay (ELISA) (Diagnostic Systems Laboratory, Webster, TX. USA) technique within the same assay, with an intraassay variance of 3.2%. Serum adiponectin was measured in duplicate using an enzyme immunoassay (APLCO Diagnostics, Salem, NH. USA) within the same assay. Intra-assay variance was ≤ 5%. Statistical analysis Statistical analyses (Student's t-test and ANOVA) were performed using the Statistical Package for the Social Sciences (SPSS) software. Graphical representations of relative changes in measured variables were performed using Sigma Plot statistical package. Results The 120 volunteers (mean age 34, range 19–50) were divided into 2 groups, with 60 randomly assigned to placebo and 60 to IGOB131 (active). Of these initial 120 volunteers, 102 completed the 10 week study; 50 from the placebo group, and 52 from the IGOB131 group. Eighteen http://www.lipidworld.com/content/8/1/7 volunteers [placebo (n = 12) and IGOB131 (n = 6)] dropped out of the study for the following reasons – not experiencing rapid weight loss (n = 10); influenza attack (n = 3); dryness of mouth (n = 3); no reason given (n = 2). Food Intake The mean daily energy intake in the IGOB131 group was 2767 ± 187 kcal of which 56% was from carbohydrate, 29% from protein, and 15% from fat. In the placebo group, the mean daily energy intake was 3156 ± 185 kcal of which 56% was from carbohydrate, 29% was from protein, and 15% was from fat. Seven-day dietary and activity assessment of the subjects at baseline showed similar food intake habits and energy levels. Body weight, waist size and body fat Baseline characteristics of the two groups were wellmatched and without significant differences at baseline (Table 1). There were no significant differences in the baseline body weight, waist circumference and serum leptin measurements between the placebo and experimental group (Table 1). However, by the tenth week, significant differences were observed between the placebo and experimental intervention groups, respectively, for body weight (95.7 kg vs. 85.1 kg, respectively, p < 0.01), waist circumference (101.1 cm vs. 88.1 cm, respectively, p < 0.05). Body fat decreased over time in both groups but the experimental group lost significantly more body fat (6.3%, p < 0.05) compared to the placebo group (1.9%) (Table 1). When corrected for placebo response, the pattern of relative changes in weight and waist circumference was found to be different between the two groups, consistent with a difference in response to the intake of the extract (Figure 1). Total and LDL cholesterol, C-reactive proteins, leptin These variables decreased from baseline, though at different rates and magnitudes associated with duration of the study, with the experimental group showing statistically significant changes compared with the placebo group at week-10 (Table 1). While baseline levels of serum lipids were similar in the two groups, significant differences were observed between the two as the study progressed with the experimental group showing progressively greater improvement. At week-10, significant differences were observed for total cholesterol (placebo: 142.5 mg/dl vs. IGOB131: 111.9 mg/dl, p < 0.05) and LDL cholesterol (placebo: 77.7 mg/ dl vs IGO131: 59.77 mg/dl, p < 0.01). Compared to baseline values, total cholesterol decreased by 1.9% in the placebo group as opposed to 26.2% for the IGOB131 group while LDL cholesterol levels fell by 4.8% in the placebo compared to 27.3% in the IGOB131 group. Correcting for Page 3 of 7 (page number not for citation purposes) Lipids in Health and Disease 2009, 8:7 http://www.lipidworld.com/content/8/1/7 Table 1: Changes* in body weight, waist, leptin, fat, total cholesterol, LDL cholesterol, glucose and adiponectin measurements in the course of the study. Time (weeks) Variables Group Base line 4 8 10 Over change Weight (Kg) Placebo IGOB131 96.4 ± 12.3 97.9 ± 9.1 95.8 ± 8.2 94.3 ± 5.5 a 95.1 ± 10.6 89.7 ± 4.7 a 95.7 ± 15.2 85.1 ± 3.1b -0.7 -12.8 Waist (cm) Placebo IGOB131 106.4 ± 10.8 105.1 ± 6.3 102.7 ± 10.6 98.0 ± 8.4a 101.1 ± 14.8 90.1 ± 8.70a 101.1 ± 15.8b 88.1 ± 7.6 -5.3 -16.19 Leptin (ng/ml) Placebo IGOB131 31.3 ± 1.8 32.9 ± 1.6 29.4 ± 1.4 18.1 ± 1.3a 28.1 ± 1.8 16.8 ± 1.2a 28.4 ± 1.8 16.9 ± 1.3b -2.9 -16.0 Fat (%) Placebo IGOB131 34.7 ± 8.6 34.2 ± 7.9 33.31 ± 10.9 31.6 ± 5.4a 32.9 ± 11.9 28.2 ± 6.6a 32.7 ± 15.7 27.9 ± 5.5a -1.99 -6.3 LDL cholesterol (mg/dL) Placebo IGOB131 77.4 ± 9.2 82.2 ± 8.1 76.5 ± 8.9 71.8 ± 5.9b 74.1 ± 9.3 64.7 ± 8.9b 73.7 ± 8.3 59.8 ± 5.0b -3.75 -22.44 Total cholesterol (mg/dL) Placebo IGOB131 145.2 ± 22.4 151.7 ± 18.5 143.9 ± 12.2 133.7 ± 16.6a 142.1 ± 13.6 120.1 ± 11.9 a 142.4 ± 12.1 111.9 ± 5.8a -2.8 -39.8 C-reactive protein (mg/L) Placebo IGOB131 1.46 ± 0.05 1.49 ± 0.041 1.46 ± 0.04 0.91 ± 0.05a 1.445 ± 0.03 0.71 ± 0.04b 1.455 ± 0.05 0.72 ± 0.05b -0.01 -0.78 81.4 ± 9.6 85.55 ± 5.59 79.5 ± 10.1 76.6 ± 10.3a 77.8 ± 9.4 68.7 ± 9.3a 77.1 ± 7.8 66.3 ± 4.9a -4.3 -19.3 12.1 ± 3.2 12.2 ± 3.0 15.2 ± 3.5 24.8 ± 3.8a 14.6 ± 3.5 31.0 ± 4.0b 14.94 ± 3.9 31.6 ± 3.9a + 2.8 + 19.4 Glucose (mg/dL) Adiponectin (mg/L) aP Placebo IGOB131 Placebo IGOB131 < 0.05; b P < 0.01 compared with Placebo placebo values, the relative change in the total cholesterol and LDL cholesterol was observed to follow a similar pattern (Figure 2) in the experimental group, suggesting a similar response mechanism to IGOB131 intake. Like in the case of the other parameters measured, C-reactive protein and leptin levels decreased over time in both groups. The rate of decrease was however accelerated in the IGOB131 relative to the placebo-group. Serum levels of CRP fell by 1.2% in the placebo group as opposed to 52.0% in the experimental group relative to baseline. On the other hand, leptin levels decreased by 9.3% in the placebo group compared to a 48.6% in the IGOB131 group over the 10-week experimental period. Fasting blood glucose levels Blood glucose levels in the experimental group (85.6 mg/ dl ± 5.6 mg/dl) and in the placebo group (81.4 ± 9.6 mg/ dl) were similar at baseline but decreased to significantly different levels (P < 0.05) at week-10 of the study (Table 1). In relative terms, decreases in placebo and treatment groups were 5.3% vs. 22.5%, respectively (Figure 3). Corrected for the placebo values, the changes in blood glucose levels were similar to that of lipids (Figure 2). Adiponectin levels Baseline serum adiponectin levels were comparable between the two groups (placebo: 12.1 mg/l ± 3.21 mg/l; IGOB131: 12.16 mg/l ± 3.04 mg/l), but increased with time (Table 1). By week-10 of the study adiponectin levels in the placebo group increased by 23.4% compared to 159.8% in the experimental group. Corrected for placebo values, the rate of increase in serum adiponectin levels in IGOB131 group followed an exponential curve (Figure 4). Adverse events Treatment of overweight and obese subjects with IGOB131 was well-tolerated. Adverse events with an incidence >n = 3 included headache (n = 5), sleep difficulty (n = 6), and intestinal flatulence (n = 6). The incidence of all reported side effects was similar in the placebo group as well as in the treatment group. Page 4 of 7 (page number not for citation purposes) Lipids in Health and Disease 2009, 8:7 http://www.lipidworld.com/content/8/1/7 suggests a favorable impact upon adipogenesis associated with IGOB131. 102 Weight Waist size Variation of baseline(%) 100 Insulin resistance is the hallmark of the metabolic syndrome and is strongly associated with excess adiposity [16]. A variety of adipocyte-derived biologically active molecules have been identified, including leptin, resistin, TNF-α, and IL-6, that may contribute to obesity-linked metabolic abnormalities [17]. Since plasma leptin levels are closely correlated with the level of adipose tissue [18], the decreases in plasma leptin level associated with IGOB131 treatment may be attributable to the decrease of adipose tissue induced as a consequence of weight loss. 98 96 94 92 90 88 86 0 2 4 6 8 10 Time (weeks) Figurein1in Changes ments IGOB131 body weight groupand corrected waist circumference for placebo values measureChanges in body weight and waist circumference measurements in IGOB131 group corrected for placebo values. Discussion The present study suggests that IGOB131, a seed extract of Irvingia gabonensis, safely and significantly reduces body weight in overweight and/or obese subjects, and has a favorable impact upon a variety of other metabolic parameters. The current clinical study shows IGOB131 administration is associated with increases in plasma adiponectin levels and decreases in leptin and CRP levels in comparison with the placebo group. These observations support the results of a recent in vitro study [12] which Body fat Total cholesterol LDL Cholesterol Fasting blood glucose Leptin C-reactive protein 100 90 % change 80 y y0 ae bx 70 According to McTernan et al. [17], adipose tissue plays a prominent role in the clinical expression of metabolic syndrome, most likely mediated by the increased release and peripheral tissue action of non-esterified fatty acids and by the dysregulated production of adipocyte-secreted proteins, including leptin, adiponectin, resistin, TNF-α, and IL-6. Adiponectin, known to correlate with endothelial function and vascular health, is exclusively expressed in adipose tissue and abundant in human plasma, and appears to be decreased in individuals with obesity and type 2 diabetes, risk factors for atherosclerosis[19]. The observation of a significant weight loss, as well as an increase in adiponectin is consistent with earlier reports in the literature observing an association between weight loss and an increase in adiponectin levels [20]. IGOB131 is relatively rich in plant-derived protein and antioxidants. A study by Baum et al, [21] had earlier shown a reduction of both total cholesterol and triglycerides levels in a hypercholesterolemic man who was fed a plant protein diet. Other studies have shown metabolic syndrome-preventive activity of antioxidant components (e.g. vitamin C, polyphenols). A number of polyphenols such as epigallocatechin gallate have anti-obesity activity and may improve metabolic disorders via modulation of adipokines and growth factors, including metabolic improvement of leptin function [22-24]. Although the active principles of IGOB131 have not yet been fully identified, it is possible that it contains some of the above mentioned compounds. 60 50 40 0 2 4 6 8 10 Figurefor Changes rected 2inplacebo measured values characteristics in IGOB131 group corChanges in measured characteristics in IGOB131 group corrected for placebo values. In conclusion, Irvingia gabonensis extract administered twice a day to healthy, overweight and obese individuals resulted in both weight reduction (body weight, body fat, waist size) and an improvement in metabolic parameters associated with insulin resistance. The current results suggest that IGOB131 may be a helpful adjunct in the management of overweight and/or obesity, supporting previous suggestions from our laboratory [25]. Page 5 of 7 (page number not for citation purposes) Lipids in Health and Disease 2009, 8:7 http://www.lipidworld.com/content/8/1/7 30 20 10 % Change 0 WT WS FAT TCHOT LDL GLU LEP CRP ADIP Placebo -10 IGOB131 -20 -30 -40 -50 Glucose Figure Percentage 3(GLU), decrease Leptin in (LEP), body weight C-reactive (WT), protein Waist(CRP) size (WS), and Adiponectin Fat (FAT), Total (ADIP) Cholesterol after 10 weeks (TCHOL), of useLDL of extract cholesterol IGO131 (LDL), Percentage decrease in body weight (WT), Waist size (WS), Fat (FAT), Total Cholesterol (TCHOL), LDL cholesterol (LDL), Glucose (GLU), Leptin (LEP), C-reactive protein (CRP) and Adiponectin (ADIP) after 10 weeks of use of extract IGO131. 140 Adiponectin 120 % of change 100 80 y y0 ae(1 e bx ) 60 40 20 0 0 2 4 6 8 10 Time (week) Figure 4in the adiponectin levels in IGOB131 group corrected for placebo Changes Changes in the adiponectin levels in IGOB131 group corrected for placebo. Page 6 of 7 (page number not for citation purposes) Lipids in Health and Disease 2009, 8:7 http://www.lipidworld.com/content/8/1/7 Competing interests 16. Part of the funds for carrying out this study was provided by Gateway Health Alliances Inc., through their "Encouragement of Research in developing countries Initiative". 17. Authors' contributions 18. JEO conceived, designed and coordinated the work, as well as prepared the manuscript; CMFM was involved in the co-design of the work as well as the draft of the manuscript. JLN carried out analytical work, BCE carried out analytical work and contributed in drafting the manuscript; CBN carried out analytical and statistical analysis. All authors read and approved the final manuscript. 19. 20. 21. Acknowledgements The LNNB is grateful to Gateway Health Alliances Inc. (Fairfield, California, USA) for preparing and supplying the Irvingia gabonensis extract (IGOB131). The authors are extremely grateful to Dr. Kenneth Blum of Wake Forest University School of Medicine, North Carolina for reviewing this article. 22. 23. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. Conway B, Rene A: Obesity as a disease: no lightweight matter. Obes Rev 2004, 3:145-51. Pasquet P, Temgoua LS, Melaman SF, Froment A, Rikong AH: Prevalence of obesity and overweight for urban adults in Cameroon. Annal of Human Biology 2003, 30:551-562. Caballero B: Introduction Symposium. Obesity in developing countries, Biological and ecological factors. J Nutr 2001, 131(3):866-870. Lee K, Sobal J: Socio-economic, dietary, activity, nutrition and body weight transitions in South Korea. Public Health Nutr 2003, 6(7):665-674. Reaven GM: Role of insulin resistance in human disease. Diabetes 1989, 37:1595-1607. NCEP – National Cholesterol Education Program: Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002, 106:3143-3121. Mandob DE, Ngondi JL, Fomekong GI, Agbor GA, Oben JE: Prediction and prevalence of metabolic syndrome in overweight and obese subjects in Cameroon. International J of Biomedical and Pharmaceutical Sciences 2008, 2:117-121. Goodpaster BH, Kelley DE, Wing RR, Meier A, Thaete FL: Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes 1999, 48:839-847. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM: Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002, 346:393-403. Ngondi J, Oben J, Minka R: The effect of Irvingia gabonensis seeds on body weight and blod lipids of obese subjects in Cameroon. Lipids in Health & Disease 2005, 4:12. Ngondi JL, Djiotsa EJ, Fossouo Z, Oben J: Hypoglycaemic effect of the methanol extract of Irvingia gabonensis seeds on streptozotocin diabetic rates. Afr J Trad Cam 2006, 3(4):74-77. Oben J, Ngondi JL, Blum K: Inhibition of Irvingigia gabonensis seed extract (OB131) on adipogenesis as mediated via down regulation of the PPARy and Leptin genes and up-regulation of the adiponectic gene. Lipids in Health and Disease 2008, 7:44. Trinder P: Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem 1969, 6:24. Richmond W: Preparation and properties of a cholesterol oxidase from Nocardia sp. and its application to the enzymatic assay of total cholesterol in serum. Clin Chem 1973, 19:1350-1356. Buccolo G, David H: Quantitative determination of serum triglycerides by the use of enzymes. Clin Chem 1973, 19:476-482. 24. 25. Maison P, Byrne CD, Hales CN, Day NE, Wareham NJ: Do different dimensions of the metabolic syndrome change together over time? Evidence supporting obesity as the central feature. Diabetes Care 2001, 24:1758-1763. McTernan CL, McTernan PG, Harte AL, Levick PL, Barnett AH, Kumar S: Resistin, central obesity, and type 2 diabetes. Lancet 2002, 359:46-47. Friedman JM, Halaas JL: Leptin and the regulation of body weight in mammals. Nature 1998, 395:763-770. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA: Hypoadiponectinemia in obesity and type 2 diabetes, close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001, 86:1930-1935. Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsuzawa Y, Chao CL, Chen CL, Tai TY, Chuang LM: Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 2001, 86:3815-3819. Baum JA, Teng H, Erdman JW Jr, Weigel RM, Klein BP, Persky VW, Freels S, Surya P, Bakhit RM, Ramos E, Shay NF, Potter SM: Longterm intake of soy protein improves blood lipid profiles and increases mononuclear cell low-density-lipoprotein receptor messenger RNA in hypercholesterolemic, postmenopausal women. Am J Clin Nutr 1998, 68:545-551. Kao YH, Hiipakka RA, Liao S: Modulation of obesity by a green tea catechin. Am J Clin Nutr 2000, 72(5):1232-1234. Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, Ohashi K, Sakai N, Shimomura I, Kobayashi H, Terasaka N, Inaba T, Funahashi T, Matsuzawa Y: Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 2002, 106:2767-2770. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T: Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002, 8:1288-1295. Ngondi JL, Fossouo Z, Djiotsa EJ, Oben J: Glycaemic variations after administration of Irvingia gabonensis seeds fractions in normoglycemic rats. Afri J Trad Cam 2006, 4:94-10. Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime." Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 7 of 7 (page number not for citation purposes) Online Submissions: wjg.wjgnet.com wjg@wjgnet.com doi:10.3748/wjg.15.3073 World J Gastroenterol 2009 July 7; 15(25): 3073-3085 World Journal of Gastroenterology ISSN 1007-9327 © 2009 The WJG Press and Baishideng. All rights reserved. EDITORIAL A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity Shirin Hasani-Ranjbar, Neda Nayebi, Bagher Larijani, Mohammad Abdollahi Shirin Hasani-Ranjbar, Neda Nayebi, Bagher Larijani, Endocrinology and Metabolism Research Center, and Faculty of Medicine, Tehran University of Medical Sciences, Tehran 1411413137, Iran Mohammad Abdollahi, Faculty of Pharmacy, and Pharmaceutical Sciences Research Centre, Tehran University of Medical Sciences, Tehran 1417614411, Iran Author contributions: Hasani-Ranjbar S completed the bibliography and drafted the paper; Nayebi N carried out the literature search and provided tables; Larijani B read the paper and commented; Abdollahi M supervised, reviewed and edited the paper. Correspondence to: Mohammad Abdollahi, Professor, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran. mohammad.abdollahi@utoronto.ca Telephone: +98-21-66959104 Fax: +98-21-66959104 Received: March 17, 2009 Revised: May 1, 2009 Accepted: May 8, 2009 Published online: July 7, 2009 Abstract This review focuses on the efficacy and safety of effective herbal medicines in the management of obesity in humans and animals. PubMed, Scopus, Google Scholar, Web of Science, and IranMedex databases were searched up to December 30, 2008. The search terms were “obesity” and (“herbal medicine” or “plant”, “plant medicinal” or “medicine traditional”) without narrowing or limiting search elements. All of the human and animal studies on the effects of herbs with the key outcome of change in anthropometric measures such as body weight and waist-hip circumference, body fat, amount of food intake, and appetite were included. In vitro studies, reviews, and letters to editors were excluded. Of the publications identified in the initial database, 915 results were identified and reviewed, and a total of 77 studies were included (19 human and 58 animal studies). Studies with Cissus quadrangularis (CQ), Sambucus nigra , Asparagus officinalis , Garcinia atroviridis , ephedra and caffeine, Slimax (extract of several plants including Zingiber officinale and Bofutsushosan) showed a significant decrease in body weight. In 41 animal studies, significant weight loss or inhibition of weight gain was found. No significant adverse effects or mortality were observed except in studies with supplements containing ephedra, caffeine and Bofutsushosan. In conclusion, compounds containing ephedra, CQ, ginseng, bitter melon, and zingiber were found to be effective in the management of obesity. Attention to these natural compounds would open a new approach for novel therapeutic and more effective agents. © 2009 The WJG Press and Baishideng. All rights reserved. Key words: Animal; Herbal medicine; Human; Obesity Peer reviewers: Cheng Ji, Professor of Research, Department of Medicine, University of Southern California, 2011 Zonal Ave., HMR-101, Los Angeles, CA 90033, United States; Anders E Lehmann, PhD, Associate Professor, Senior Principal Scientist, Bioscience, AstraZeneca R&D Mölndal, Mölndal, Sweden Hasani-Ranjbar S, Nayebi N, Larijani B, Abdollahi M. A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity. World J Gastroenterol 2009; 15(25): 3073-3085 Available from: URL: http://www.wjgnet. com/1007-9327/15/3073.asp DOI: http://dx.doi.org/10.3748/ wjg.15.3073 INTRODUCTION The prevalence of obesity is increasing worldwide [1] resulting in an association with major health problems such as type 2 diabetes, ischemic heart disease, stroke, and cancer. It is necessary to treat obese individuals by both lifestyle interventions and/or pharmacological therapy. Phar macologic treatment and surgical interventions used in some circumstances are not always appropriate[2]. Unfortunately, drug treatment of obesity despite short-term benefits, is often associated with rebound weight gain after the cessation of drug use, side effects from the medication, and the potential for drug abuse[3]. Pharmacologic options include sibutramine, orlistat, phentermine, diethylpropion, and fluoxetine or bupropion. Phentermine and diethylpropion have potential for abuse and are only approved for shortterm use. Approved medications for long term use in the treatment of obesity are sibutramine and orlistat, however, these agents should be used with caution in patients with a history of cardiovascular disorders [4]. The general public uses many other methods for weight www.wjgnet.com 3074 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol loss including herbs, vitamins, nutritional supplements, and meal replacement preparations. Rigorous scientific studies have not been carried out on these products, and in many cases safety and efficacy take a back seat to marketing. Complementary and alternative therapies have long been used in the Eastern world but recently these therapies are being used increasingly worldwide[5]. When conventional medicine fails to treat chronic diseases and conditions such as obesity efficaciously and without adverse events, many people seek unconventional therapies including herbal medicine [6]. Although the number of randomized trials on complementary therapies has doubled every 5 years and the Cochrane library included 100 systematic reviews of unconventional inter ventions [7] , none of these studies specifically mentioned herbal therapy in obesity. This review aimed to evaluate the current science on the efficacy and safety of herbal medicines in the management of obesity. DATA SOURCES AND STUDY SELECTIONS PubMed, Scopus, Google Scholar, Web of Science, and IranMedex databases were searched up to December 30, 2008 for all human and animal studies investigating the effects (both harmful and beneficial) of treating obesity with herbal medicines. The search terms were “obesity” and (“herbal medicine” or “plant”, “plant medicinal” or “medicine traditional”) without narrowing or limiting search elements. Only publications with available abstracts were reviewed. The main outcome measures sought at the end of treatments as anti-obesity effects, were body weight, body fat including fat mass/fat weight or fat percentage/visceral adipose tissue weight, triceps skin fold thickness, waist or hip circumference, and appetite or amount of food intake. Herbal medicines are defined in this review as raw or refined products derived from plants or parts of plants (e.g. leaves, stems, buds, flowers, roots, or tubers) used for the treatment of diseases. The synonyms of herbal medicines are herbal remedies, herbal medications, herbal products, herbal preparations, medicinal herbs, and phytopharmaceuticals, etc. All of the abstracts from human and animal studies with the main outcome of change in anthropometric measures such as body weight and waist-hip circumference, body fat (weight or mass of visceral adipose tissue, fat mass or percent), amount of food intake, and appetite in participants were included. Even studies on other relevant diseases such as diabetes were also reviewed and included if the appropriate outcomes were shown. In vitro studies, review articles, and letters to the editor were excluded. Unpublished data such as theses were also excluded. Two reviewers independently examined the title, abstract and references of each article meeting the inclusion criteria and eliminated duplications and those showing exclusion criteria. July 7, 2009 Volume 15 Number 25 FINDINGS Of the publications identified from the initial database search, 915 results were identified and reviewed for inclusion or exclusion. A total of 77 studies were included (19 human and 58 animal studies). Human studies included 17 randomized clinical trials (RCTs) and two before-after clinical trials[8-26]. RCTs reported random allocation of humans to herbal medicines vs (placebo/another plant/combination of plants) with or without specific dietary and exercise programs outlined in Tables 1 and 2 as weight loss programs. Human subjects were healthy overweight, obese or with impaired glucose tolerance test volunteers. Animal studies included healthy, genetically or experimentally obese or diabetic mice, rats and other rodents. The route of administration of herbs in almost all studies was oral intake with the exception of some animal studies as indicated in Table 2. HUMAN STUDIES Change in human body weight All studies showed loss of body weight except one[21] which seemed to have problems with the study design, and one other study [10] which showed a significant decrease only in body fat. Studies with Cissus quadrangularis (CQ)[26] or combined with Irvingia gabonensis (IG)[15], a combination of Sambucus nigra and Asparagus officinalis[16], calcium hydroxycitrate in Garcinia atroviridis[18], supplements containing ephedra and caffeine[9,13,20], and Slimax as an extract of several plants including Zingiber officinale[8] and Bofutsushosan[14] showed significant decreases in body weight. Body fat A significant decrease in body fat was shown with CQ[26], supplements containing ephedra and caffeine[9,13], a natural compound containing capsicum and some lipotropic nutrients[10], Bofutsushosan[14], and calcium hydroxycitrate in Garcinia atroviridis [18]. These phytopharmaceuticals showed a significant decrease in triceps skin fold thickness indicating significant loss of fat. Waist and hip circumference Efficient decreases in both waist and hip circumferences in trials with a supplement containing ephedra and caffeine[9] and Slimax (extract of several plants including Zingiber officinale [8] were shown whereas Caralluma fimbriata[19] and CQ with or without IG[15] significantly decreased waist size. Food intake Decreases in appetite or amount of food or energy intake with a supplement containing ephedra and caffeine[20] and Caralluma fimbriata[19] were shown (not significant) but hydroxycitric acid (HCA-SX) with or without Gymnema sylvestre[23] decreased the amount of food intake efficiently. A natural compound containing capsicum and other lipotropic nutrients [10] did not significantly change energy intake. www.wjgnet.com Hasani-Ranjbar S et al . Herbal medicines used in the management of obesity 3075 Table 1 Human studies considering the anti-obesity effects of herbal medicines Authors Ignjatovic et al[8] 2000 Boozer et al[9] 2001 Hoeger et al[10] 1998 Target Herbs (scientific name) Healthy Slimax: extract of volunteers several plants: Hordeum vulgare, Polygonatum multiflorum, Dimocarpus longan, Ligusticum sinense, Lilium brownie, and Zingiber officinale Over wt. An herbal supplement: (n = 35 ) (Ma Huang & Guarana) Healthy A natural dietary compound of chromium picolinate, inulin, capsicum, Lphenylalanine, and other lipotropic nutrients Study Dose/duration Groups Main outcome Other relevant effects & complications RCT 6 wk C: Placebo I: Compound Sig. decrease in body wt. & waist & hip Cir. & BMI Modification of lipid metabolism with sig. effect on the accumulation & the release of lipid from adipose tissue RCT (doubleblind) 72 mg (ephedra) 240 mg (caffeine)/8 wk C: Placebo (n = 24) I: Compound (n = 24) RCT (doubleblind) 4 wk C: wt. loss program (n = 67) I: wt. loss program + compound (n = 56) Greater reduction in Sig. decrease in serum TG, potentially body wt. & total treatment-related body fat & sig. greater reduction in dropouts (23%) in the active group and none hip & waist Cir. in the placebo group. Dry mouth, insomnia & headache were reported Sig. decrease in body fat percent, fat mass & FFM, but no sig. difference in body wt. BMI and energy intake Ziauddin et al[11] 2004 Hhyperlip- Terminalia arjuna Roxb idemic (n = 30) Beforeafter CT Abidov et al[12] 2006 Obese non- A compound of Aralia diabetic mandshurica (A) and women Engelhardtia chrysolepis (n = 32) (E) extracts named ARALOX RCT 450 mg (A) & 450 mg (E)/d C: Diet + placebo I: Diet + compound Greenway et al[13] 2004 Human (obese & over wt.) healthy Obese women with IGT (n = 80) Herbal supplement containing caffeine and ephedra RCT (doubleblind) 210 mg (e) & 72 mg (c)/12 wk C: Placebo I: Compound Bofu-tsusho-san containing (Ephedrae Herba, Glycyrrhizae Radix, Forsythiae Fructus, Schizonepetae Spica &…) RCT (doubleblind) Equivalent of (24 mg/ephedrine & 280 mg caffeine/24 wk) C: wt. loss program I: wt. loss program + compound Hioki et al[14] 2004 Oben et al[15] 2008 Human (obese & over wt.) A combination of Cissus quadrangularis (CQ) & Irvingia gabonensis (IG) RCT (doubleblind) 300 mg (CQ) & 500 mg (IG) per day/10 wk C: Placebo I: CQ CQ + IG Chrubasik et al[16] 2008 Healthy (n = 80) A combination of Sambucus nigra (S) and Asparagus officinalis (A) Beforeafter CT (S): 1 mg anthocyanin, 370 mg flavonol, 150 mg hydroxycinnamate (A): 19 mg saponin per day - www.wjgnet.com Sig. improvement Sig. decrease in serum in obesity. total lipid levels. Sig. Reduction in body relief of palpitation, wt. in some cases dyspnea, chest & joint pain. Reduction in BP in some cases Decrease in total Reduction in perilipin body wt. & fat wt. content in adipocytes and plasma TG. Stimulate activity of hormone sensitive lipase Sig. decrease in No differences in lipid body wt. & the levels, or BP were percentage of fat shown. No serious adverse effect No decrease in RMR. Compared to Sig. improvement baseline the I group in insulin resistance lost significantly compared to more body wt. & abdominal visceral week 0. Loose bowel fat & the placebo movements resulted in three withdrawals group lost sig. body wt. & had no sig. change in abdominal visceral fat Sig. decrease in Chol Sig. decrease in & LDL of plasma and body wt. & body fat percent & waist fasting blood glucose levels size in both I groups but the combination group (CQ + IG) resulted in larger reductions Sig. decrease in Sig. improvement mean of the wt. of BP, physical and emotional well-being and quality of life 3076 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol Udani et al[17] 2007 Healthy (n = 25) Proprietary fractionated white bean extract RCT (doubleblind) 2000 mg/14 wk Roongpisu thipong et al[18] 2007 Obese women Calcium hydroxycitrate in Garcinia atroviridis RCT 2 mo Kuriyan et al[19] 2007 Over wt. (n = 50) Caralluma fimbriata RCT 1 g/60 d Hackman et al[20] 2007 Obese & over wt. women (n = 41) Multinutrient supplement containing ephedra (e) and caffeine (c) RCT (doubleblind) 40 mg (e) and 100 mg (c)/9 mo Garrison [21] et al 2006 Over wt. women Proprietary extracts of Magnolia officinalis and phellodendron amurense RCT 750 mg/6 wk Coffey et al[22] 2004 Human (over wt. & obese) (n = 102) Product containing ephedrine, caffeine & other ingredients. RCT (doubleblind) 12 wk [23] Obese (n = 60) Hydroxycitric acid (HCA -SX) and a combination of HCA-SX and niacinbound chromium (NBC) and Gymnema sylvestre extract (GSE) RCT (doubleblind) HCA-SX: 4667 mg GSE: 400 mg NBC: 4 mg/8 wk [24] Obese (n = 24) A proprietary fractionated white bean (Phaseolus vulgaris) RCT (doubleblind) 3000 mg/8 wk Bhatt et al[25] 1995 Healthy (n = 58) Guggulu (Medohar) RCT 1/5, 3 g/30 d Oben et al[26] 2007 Over wt. & obese Cissus quadrangularis RCT (doubleblind) 300, 1028 mg Preuss et al 2004 Udani et al 2004 July 7, 2009 Volume 15 Number 25 C: Placebo + wt. loss program I: Extract + wt. loss program In both groups, There were no decrease in body adverse effect wt. & waist size from baseline was sig. but no sig value between groups C: Diet Sig. decrease in I: Diet + extract body wt. & greater reduction in BMI. Sig. decrease in the triceps skin fold thickness C: wt. loss Sig. decrease in program waist Cir. & hunger I: wt. loss levels. Greater program + decrease in body extract wt., BMI, hip Cir., body fat & energy intake but not sig. C: Control Sig. decrease in Sig. decline in serum supplement body wt. decrease chol, TG, glucose, I: Multinutrient in appetite fasting insulin & leptin supplement levels & minor adverse effects like dry mouth, insomnia, nervousness and palpitation were reported C: Placebo No sig. wt. gain The I groups tended I: Extract for the I group to have lower levels of but sig. wt. gain cortisol in the evening in C. groups C: Placebo Additional wt. loss No difference in pulse, I: Compound (1/5 kg) & greater diastolic & systolic BP reduction in BMI & adverse events & waist Cir. No difference in body fat & fat mass percent was shown C: Placebo 5%-6% decrease in Sig. decrease in serum I1 = HCA-SX body wt. & BMI lipids & leptin & I2 = GSE + NBC & sig. decrease in increase in HDL & + HCA-SX food intake in excretion of urinary All groups both I groups fat metabolites in both had wt. loss I groups. There were program mild adverse effects but not significant between groups C: Placebo Decrease of body Reduction of TG three I: Extract wt. with 129% times greater than difference C. group. No adverse effect was shown C: wt. loss Higher mean wt. program reduction I: wt. loss in I group. program + In I group, all extract patients > 90 kg lost wt. but 3 in C group did not lose wt. C: Placebo Sig. decrease in Sig. decrease in serum I: Two extract body wt & lipids and glucose. formulation: body fat Sig. increase in HDL-C CQR-300, CORE plasma 5-HT and creatinine levels Cir: Circumference; BP: Blood pressure; BMI: Body mass index; sig.: Significant; C: Control; I: Intervention; RCT: Randomized control trial; CT: Clinical trial; TG: Triglyceride; HDL: High density lipoprotein; LDL: Low density lipoprotein; Chol: Cholesterol; IGT: Impaired glucose tolerance. Other effects Anti-hyperlipidemic, antihyperglycemic, and other relevant anti-obesity effects of medicinal plants in human studies are summarized in Table 1. Adverse effects No significant adverse effects compared to controls were mentioned and no mortality was reported, except in studies with supplements containing ephedra and www.wjgnet.com Hasani-Ranjbar S et al . Herbal medicines used in the management of obesity 3077 Table 2 Animal studies on the anti-obesity effects of herbal medicines Authors Target Herbs (scientific name) Dose/duration Groups Main outcome Other relevant effects & complications Wang et al[27] 2000 Rat (obese) (2.5 g/kg) - Sig. decrease in Lee’s index & size of fat cells Did not influence the function of thyroid gland & metabolism of water & salt Jeon et al[28] 2003 Mouse Haidonghua powder: Laminaria japonica Aresch & Benincasa hispida (Thunb.) Cogn. etc Rhus vemiciflua Stokes 8 wk C: HFD I: HFD + extract AlarconAguilar et al[29] 2007 Mouse Hibiscus sabdariffa 120 mg/kg 60 d Urías-Silvas et al[30] 2008 Mouse Fructans extracted from Agave tequilana (TEQ) and Dasylirion spp (DAS) 10% supplement Park et al[31] 2007 Rat Platycodon grandiflorum 150 mg/kg 7 wk Jongwon et al[32] 2005 Rat (obese by HFD) Allium victorialis var. platyphyllum leaves 100 mg/kg 2 wk Kobayashi et al[33] 2001 Rat Evodiamine an alkaloid of a fruit: Evodia rutaecarpa 0/02%, 0/03% of the diet 12 wk Jin et al[34] 1994 Rat Jiang-zhi jian-fei yao: the refined Rhubarb Injected intragastrically Kim et al[35] 2008 Rat Juniperus chinensis 1% supplement /79 d Shih et al[36] 2008 Mouse (obese by HFD) Momordica charantia (bitter melon) 4 wk Pang et al[37] 2008 Rat (obese by HFD) Ilex paraguariensis Bruno et al[38] 2008 Mouse Green tea 0%, 1%, 2% (wt.:wt.)/6 wk Sig. suppression of body wt. gain and lower wt. of subcutaneous adipose tissue C: Healthy & Sig. decrease in body obese (by MSG) + wt. gain in obese mice placebo & increased liquid I: Same groups + intake in both groups extract C: STD Sig. decrease in body I: STD + wt. gain & food intake. Raftilose/ The (TEQ) group had DAS/TEQ the lowest value Lowered plasma TG No sig. change in TG & Chol levels. Increase in ALT levels was shown but was not sig. Lower serum glucose & Chol level but Sig. decrease in TG levels was shown in Raftilose group. Higher concentration of GLP-1 & it's precursor & proglucagon mRNA in I groups C: NLD/HFD Sig. decrease in body Sig. decrease in plasma TG wt & subcutaneous I: Same groups & Chol concentrations, upadipose tissue wt. & + extract regulation of FABP mRNA adipocytes size in I expression induced by HFD group Considerable reduction Sig. decrease in hyperlipidemia of retroperitoneal, and increased lipid content in epididymal and total feces abdominal fat pad wt. C: Control Sig. decrease in Sig. decrease of lipid in liver & serum FFAs. Sig. increase of I: Extract perirenal fat wt. & decrease of epididymal lipolytic activity in perirenal fat tissue & specific GDP fat mass binding in brown adipose tissue mitochondria as the biological index of heat production No sig. increase in Prolongation of stomach body wt. but reduction evacuation time and of food intake. acceleration of intestinal Decreased size of movements abdominal adipose cells C: NLD/HFD Sig. decrease in body Sig. decrease in blood lipid, leptin & insulin levels. Sig. I: HFD + extract wt gain & visceral fat reversal of the down-regulation pad wt. of genes implicated in adipogenesis & increased gene expressions & phosphorylations related to FABO C: Control Sig. decrease in Sig. improvement in blood epididymal white glucose, leptin, and FFA. I: Rosiglitazone/ adipose tissue wt. & Influenced PPARα/ extract visceral fat wt. PPARγ expression Sig. decrease in body Sig. decrease in blood and wt. of visceral fat-pad hepatic lipid, glucose, insulin and leptin levels. Reversed wt. the down-regulation of genes implicated adipogenesis, thermogenesis & enhanced expression of uncoupling proteins in adipose tissue C: Obese/lean Sig. decrease in body In obese I group, sig. decrease in hepatic steatosis was I: Same groups wt. of both I groups observed dose dependently. + extract Liver enzymes decreased. 30%-41% and 22%-33% lower serum ALT and AST activities were shown, respectively www.wjgnet.com 3078 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol Lee et al[39] 2008 Mouse A combination of Morus alba, Melissa officinalis and Artemisia capillaries 12 wk - Choi et al[40] 2008 Mouse (obese by HFD) Cucurbita moschata 500 mg/kg 8 wk _ Huang et al 2008[41] Rat Lemaure et al[42] 2007 Rat (obese) Salacia reticulata 0/5% 8 wk in mice 0/2% 35 d in rats 1 g/kg (A), 500 mg/kg (u) 8 wk C: HFD I: HFD + plant 1% (wt:wt) /12 wk C: HFD I: HFD + extract Lei et al[43] 2007 Mouse Aoki et al[44] 2007 Mouse (obese by HFD) Oluyemi et al[45] 2007 Rat Han et al[46] 2006 Mouse (obese by HFD) Goyal et al[47] 2006 Mouse (obese gold thioglucose) Rat and mouse Kishino et al[48] 2006 Jayaprakasam et al[49] 2006 Mouse July 7, 2009 Volume 15 Sig. decrease in body wt. gain & adipose mass Number 25 Decreased serum levels of TG, Chol & inhibited hepatic lipid accumulation, and increased hepatic mRNA levels of enzymes responsible for FABO Sig. suppression of body wt. & fat storage increase but amount of food intake was not affected Momordira charantia L. 5% C: HFD Sig. decrease in the Sig. decrease in enzymes of (Bitter melon) I1: HFD + plant number of large adipose tissue implicating I2: HFD + adipocytes in both I reduction of insulin resistance thiazolidinedione groups. Sig. decrease in I group as compared to in adipose tissue mass C group in I1 group compared to I2 group Cyperus rotundus 45, 220 mg/kg _ Sig. decrease in wt. L. tubers 60 d gain without affecting food consumption Pomegranate leaf 400/800 mg C: HFD/NLD Sig. decrease in body Sig. decrease in serum TG, per kilogram I: Same groups wt. & energy intake Chol, glucose levels & Chol/ 5 wk + extract and adipose pad wt. HDL ratio, inhibition of percents in I. group. intestinal fat absorption Sig. decrease in appetite of obese mice on NLD was shown Licorice flavonoids 0/5%, 1%, 2% C: Placebo Sig. decrease of Improvement of fatty oil (LFO) 8 wk I: Extract abdominal white degeneration of hepatocytes and adipose tissue & body changes in genes implicating wt. gain with 1% & 2% regulation of lipid metabolism LFO groups, decrease with 2% concentration of adipocyte size Garcinia cambogia 200, 400 mg/kg C: Placebo Sig. decrease in Sig. decrease in TG pool of seed (bitter cola) 5 wk I: Extract body wt. adipose tissue & liver but sig. increase of HDL & decreased LDL Kochia scoparia 1%, 3%/3 d Prevented the Sig. increase the fecal content & increases in body & fecal TG levels in day 3 parametrial adipose tissue wt. Zingiber officinale 250 mg/kg C: Placebo Sig. decrease in Sig. decrease in serum Chol, 8 wk I: Extract body wt. TG, glucose, and insulin Cornelian cherry (cornus mas) (Purified anthocyanins (A) & ursolic acid (u) Arachis hypogaea nutshell Moreno et al[50] 2006 Rat Galisteo et al[51] 2005 Rat (obese) Plantago Ovata Zhao et al[52] 2005 Mouse (obese by hyperalimentation) Phillyrin (Fructose forsythia) Chen et al[53] 2005 Rat Bitter melon (Momordica charantia) 3/5% 25 wk 0/75% or 7/5 g per kilogram 7 wk C: HFD I: HFD + A/A +u Sig. decrease in the Sig. decrease in plasma TG, body wt. and visceral 4 h after ingestion; Sig. decrease fat mass increase in energy efficiency, plasma leptin and adiponectine levels 24% decrease in wt. Elevated insulin levels; Sig. gain in (A) group decrease of liver TG in A + u group Increased fecal lipid excretion. Reduced TG content of liver and serum glucose and insulin C: STD Sig. decrease in body Sig. improvement of lipid I: STD + extract wt. gain profile, FFA & insulin & TNF-α & hypoadinectinemia Sig. decrease in wet Decrease in jejunum microvillus wt. of fat & fat index & area, and serum levels of diameter of fat cells & TG & Chol lee index C: LFD/HFD Lower energy Reduced plasma glucose and I: LFD/HFD efficiency and visceral hepatic TG but higher serum + extract fat mass after 4 wk in FFA after 4 wk; Higher plasma I group catecholamine after 7 wk in I group; Sig. decrease in hepatic TG & steatosis and sig. increase of serum epinephrine & FFA in HFD group of I www.wjgnet.com Sig. decrease in body wt. gain and liver size Hasani-Ranjbar S et al . Herbal medicines used in the management of obesity Han et al[54] 2005 Rat Coleus forskohlii 50 g/kg Han et al[55] 2005 Mouse Chikusetsu saponins isolated from Panax japonicus rhizomes 1%, 3%/9 wk Han et al[56] 2005 Mouse Zingiber officinale Roscoe 1%, 3%/8 wk Cha et al[57] 2004 Mouse Kim et al[58] 2005 Rat Yun et al[59] 2004 Mouse Junbao et al[60] 2004 Kim et al[61] 2004 Rat (obese) Kwon et al[62] 2003 Lu et al[63] 1999 Rat Rodent C: Sham operated/ ovariectomized + control diet I: Same groups + extract C: HFD I: HFD + extract Reduced body wt.& food intake & fat accumulation Prevented body wt. gain & increase of parametrial adipose tissue wt. Sig. decrease in body wt. gain at 2-8 wk with 3% & in final parametrial adipose tissue wt. with 1% concentration HFD group of I had C: NLD/HFD Acanthopanax 0/5 g per lower wt. gain but no I: NLD/HFD senticosus kilogram difference in food + extract 12 wk consumption was shown Reduced body wt., Crude saponin of 200 mg/kg C: NLD/HFD food intake & fat Korean red ginseng 3 wk, ip I: NLD/HFD content in HFD group + extract of I similar to those fed with NLD Wild Ginseng 250, 500 mg/kg C: HFD Sig. inhibition of I: HFD + extract body wt. gain dose dependently. Decrease of white & brown adipocytes diameters Semen cassiae 6% Sig. decrease in body wt. & lee index Sig. decrease in body 50 mg/100 g C1: NLD Adlay seed wt. & food intake of body wt. C2: HFD + saline (CoixLachrymajobi var. & epididymal and (sham group) mayuen) I: HFD + plant peritoneal fat & white adipose tissue size as compared to sham group Dioscorea nipponica 5%/8 wk C: HFD Sig. decrease in body Makino I: HFD + plant wt. & adipose gain Inspissation tea (Guangdong kudingcha) Yoshikawa et al[64] 2002 Rat (obese) Salacia reticulata 125 mg/kg 27 d Xie et al[65] 2002 Mouse Ginseng berry 150 mg/kg 12 d, ip Yamamoto et al[66] 2000 Rat CT-Ⅱ, an extract from Nomame Herba 8 wk, 12 wk, 6 mo Han et al[67] 1999 Mouse Oolong tea 10 wk Sig. increase of the fecal content & TG level in day 3; reduction of plasma TG 2 h after oral lipid intake & inhibition of pancreatic lipase activity C: HFD I: HFD + plant Stronger modulation on lymphocytes hypertrophy and quantity was shown in I1 group Suppression of body wt. and periuterine fat storage increase in female rats but no effect on male rats C: Diabetic/lean Sig. decrease in body wt. as compared to day diabetic 0 in diabetic group of + placebo I: Same groups I. wt. loss in lean mice was shown + extract Sig. inhibition of C: Lean/obese body wt. gain dose + HFD I: Same groups dependently without + HFD + plant affecting food intake in lean rats after 12 wk. Sig. decrease in body wt. gain in obese mice after 24 wk C: HFD No sig. difference I: HFD + extract in food intake but prevented obesity & liver induced by a HFD C: Control I1: Extract I2: Fenfluramine Rat (obese by hyperalimentation) 3079 www.wjgnet.com In HFD group of I, lower serum LDL and restoration of liver TG at the same level as fed by LFD was shown; No alteration in carnitine status Reduction of hypothalamic NPY expression and serum leptin level in HFD group of I Sig. inhibition of FBG, TG, and FFAs dose-dependently; insulin resistance improved Reduction of fasting serum TG, insulin & malondialdehyde Increase of brown adipocytes as compared to NLD group but not significant Suppression of time dependent increase of serum TG level after lipid intake Only fenfluramine showed sig. difference in small intestine villus model Sig. increase in glucose tolerance in diabetic mice but no sig. decrease of FBG in lean mice. Sig. inhibition of TG elevation Enhancement of noradrenalin induced lipolysis & inhibition of pancreatic lipase activity 3080 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol Pusztai et al[68] 1998 Rat Kidney bean (Phaseolus vulgaris) 130, 150, 280 g/kg 10-70 d Nagasawa et al[69] 1991 Mouse (obese) Tree peony root (Paenia suffruticosa) 0/5% 30 wk Wang et al[70] 2008 Mouse Parasitic loranthus from Loranthacea or Viscaceae 20 d Hu et al[71] 2008 Mouse (female) 2%/11 wk Ohkoshi et al[72] 2007 Mouse Escins extracted from Aesculus turbinata Blume (Hippocastanaceae) Nelumbo nucifera Gaertn leaves (Nymphaceae) Kang et al[73] 2004 Rat 6 wk Mary et al[74] 2003 Rabbit PM-F2-OB composed of Lycii Fructus, Rehmanniae Radix, Coicis Semen, Carthami Flos, Hoelen, Angelicae Radix, Nelumbinis Semen, Radix Dioscorea and Aurantii Fructus Caps HT2 A herbal formulation Wu et al[75] 2005 Rat (diabetic by STZ ) Xie et al[76] 2005 Mouse (Genetically obese) Palit et al[77] 1999 Mouse Oi et al[78] 1999 50% July 7, 2009 Volume 15 Number 25 Sig. decrease of body protein in lean I group. Sig. decrease in plasma insulin levels in obese I group. Sig. pancreatic growth after long term feeding in all I groups C: Control Sig. decrease in food Improvement in glucose I: Extract intake and Lee index tolerance. No sig. difference in serum FFA levels Sig. decrease in body High inhibitory ability on FASwt. & food intake Loran thacea was nearly 400 fold stronger than that from the viscaceae Suppressed the increase of liver I: HFD Suppressed the TG content; increased TG in C: HFD + extract increase in body & feces after fat ingestion parametrial adipose tissue wt. Sig. suppression of Exhibition of lipolytic activity C: STD/HFD body wt. gain especially in visceral adipose I: Same groups tissue; β adrenergic receptor + extract pathway was partly involved Sig. decrease in serum Chol/ No sig. difference in C: STD/HFD LDL and total lipids; reduction wt. change if STD I: Same groups of kidney fat wt./FFA/PL & was used but in HFD + plant group of I resulted in TG to levels equal or below the normal diet sig. decrease in body wt. gain but showed no sig. difference in amount of food intake C: Lean/obese + LFD/HFD I: Same groups + extract - 5 mg/kg (iv) 30 d 100/200/300/ 400/mg per kilogram orally 400 mg/kg Astragalus (APS) 5 wk polysaccharide (APS) a component of Astragalus membranaceus roots C: Placebo Total, Ginsenosides in 100, 200 mg/kg I: Extract (ip) 12 wk Chinese ginseng (TG & 150, CG), from leaves and the 300 mg/kg stem of Panax ginseng (oral)/12 wk Galega officinalis 10% (w/w) of C: Diabetic/NL the diet 28 d I: Same groups + plant The growth was retarded dosedependently lower body fat Sig. decrease in body Sig. increase in HDL after oral wt. administration and decrease in atherogenic index in oral administration; Sig. increase of the release of LPL enzyme and sig. hypolipidemic effect in Ⅳ groups Sig. decrease in Sig. decrease in plasma glucose; body wt. improved insulin sensitivity Sig. decrease in body wt. Sig. decrease in body wt. in both I groups, sig. wt. loss in normal mice independent of a reduction in food intake but in diabetic mice wt. loss was with reduced food intake C: HFD Sig. decrease in I: HFD + extract body wt. & perirenal adipose tissue wt. & epididymal fat pad Rat Garlic 8 g/kg of diet 28 d Yoshida et al[79] 1995 Mouse (obese and lean) Bofu-tsusho-san 1/4%, 4/7% of wt. of food 8 wk - He et al[80] 2008 Rat (obese by STZ & HFD Yi-Qi-Yang-Yin-Ye 2, 4, 8 g/kg 4 wk - www.wjgnet.com Sig. decrease in body wt. & retroperitoneal white adipose tissue wt. and no change in food intake Body wt. decreased Sig. decrease in FBG in 200 mg/kg dose after injection Sig. decrease in FBG in 300 mg/kg dose Striking loss of body fat in both groups; Sig. decrease in serum glucose in both groups but Sig. decrease in serum insulin in diabetic mice Sig. decrease in plasma TG levels; sig. decrease in mitochondrial protein and (UCP) in brown adipose tissue, and in urinary noradrenaline and adrenaline excretion Sig. increase in GDP binding dose dependently Decrease in TG/Chol/ LDL/FFA/FBG/insulin; improvement of glucose tolerance Hasani-Ranjbar S et al . Herbal medicines used in the management of obesity Jeong et al[81] 2008 Park et al[82] 2005 Akagiri et al[83] 2008 Kim et al[84] 2005 Attele et al[85] 2002 Rat (fatty) Gyeongshang angjeehwan: Liriope platyphylla F.T./Wang & T. Tang (Liliaceae), Platycodongrandiflorum A. DC. (Campanulaceae). Schisandrachinensis K. Koch (Magnoliaceae). Ephedra sinica Stapf (Ephedraceae) Rat (obese by diet) Platycodon grandiflorum 3081 8 wk C: Placebo I: Compound Sig. decrease in food intake & body wt. gain & abdominal fat Sig. decrease in plasma leptin levels; decrease in circulating TG and inhibition of lipid accumulation in liver; increase of mRNA of genes responsible for FABO 150 mg/kg 7 wk C: Convert to NLD/HFD I: Same groups + extract Sig. decrease in wt. of body & adipose tissues in rats converted to NLD as compared to those remained on HFD The wt. of WAT and increase in size of adipocytes inhibited Sig. decrease in body wt. Sig. decrease in fat cell number & size in both I groups as compared to their state before intervention; decrease of FABP expression in HFD group of I Mouse (obese by HFD) Mouse (diabetic) Bofutsushosan (BOF) 1%/4 wk C: Placebo I: Compound Pine extract (bark and needle) 21 d C: Control I: Extract Mouse (obese diabetic) Panax ginseng berry 150 mg/kg (ip) 12 d C: Control I: Extract Sig. loss of wt. with a sig. reduction in food intake & a very sig. increase in energy expenditure & body temperature Expression of UCP1 mRNA in WAT was found but not sig. Effectively suppressed the increase of postprandial blood glucose level by delaying absorption of diet Sig. improvement in glucose tolerance & sig. reduction in serum insulin levels & plasma chol levels MSG: Monosodium glutamate; FABO: Fatty acid β oxidation; STD: Standard diet; LFD: Low fat diet; NLD: Normal diet; HFD: High fat diet; FABP: Fatty acid binding protein; FFM: Fat free mass; sig.: Significant; AST: Aspartate transaminase; ALT: Alanine transaminase; C: Control; I: Intervention; FAS: Fatty acid synthetase; UCP: Uncoupling protein; GDP: Guanosine 5' diphosphate; FAS: Fatty acid synthetase; TG: Triglyceride; HDL: High density lipoprotein; LDL: Low density lipoprotein; FBG: Fasting blood glucose; ip: Intraperitoneal; iv: Intravenous. Caps HT2 is a herbal formulation containing methanolic extract of selected parts of plants: commiphora mukul; Allium Sativum; Plumbago indica/some carpus anacardium/Hemidesmus indicus/Terminalia arjuna/Tinospora cordifolia/Withania somnifera ocimum sanctum. caffeine[9,20] which caused minor adverse effects such as dry mouth, insomnia, ner vousness, palpitation and headache. Bofutsushosan [14] caused loose bowel movements. ANIMAL STUDIES Change in body weight and body fat The majority of animal studies (41 out of 58) showed significant weight loss or inhibition of weight gain when supplemented with high fat diets containing extracts of plants, with or without an efficient decrease in fat mass[27-85] (Table 2). Food intake Clinical trials with Agave tequilana (TEQ) and Dasylirion spp (DAS)[30], Pomegranate leaf[43], Korean red ginseng[58], Tree peony[69], Gyeongshang angjeehwan containing a variety of plants including platycodongrandiflorum, Magnoliaceae and Ephedra[81], Parasitic loranthus[70], and Panax ginseng berry[85] showed significant reductions in food intake or appetite. In studies with Cucurbita moschata[40], Cyperus rotundus[42], Nomame Herba[66], Acanthopanax senticosus[57] PMF2-OB (a traditional herbal medicine used for the treatment of obesity in Korea composed of Lycii Fructus), and several other plants[73], bofu-tsusho-san[79], Galega officinalis[77], and Oolong tea[67], no change in the amount of food intake or appetite was observed. DISCUSSION In many studies[8-10,12-16,20-23,27,39,73,74,79-81,83], a combination of plants or compounds containing minerals and or chemical extracts of plants were investigated and the scientific names are summarized in Tables 1 and 2. Most of these studies showed anti-obesity effects such as decreasing body weight in humans or body weight gain in animals with or without changes in body fat. Currently available anti-obesity medications attack the body fat dilemma in three different ways. They can stimulate metabolism, suppress appetite, affect serotonin, or they can impede digestion of fat. In this review, we can categorize the target effects of herbal medicines in the same way. Arachis hypogaea[50] decreased body weight gain, liver triglyceride content and liver size in association with increased fecal lipid excretion, suggesting an inhibitory mechanism on lipid absorption. Phillyrin [52], Allium victorialis[32], Pomegranate leaf[43], Kochia scoparia[46], Panax japonicus[55], Oolong tea[67], and Aesculus turbinata Blume[71] also had the same effect. A decrease in food intake as a result of a decrease in appetite and an influence on hormonal status was observed with TEQ and DAS[30], Pomegranate leaf[43], Korean red ginseng [58], Tree peony [69], Gyeongshang angjeehwan containing a variety of plants including platycodon g randif lor um and Magnoliaceae and www.wjgnet.com 3082 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol ephedra[81], and Parasitic loranthus[70], refined Rhubarb[34], Caralluma fimbriata[19] and Panax ginseng berry[85]. Possible stimulation of metabolism has been reported as a mechanism of action for compounds such as Slimax[8], supplements containing ephedra[9,13,14,20] and Terminalia arjuna Roxb [11] which showed modification of lipid metabolism and a reduction in serum lipid levels. Ephedra known as Ma Huang is a well known natural product with amphetamine-like stimulation effects. Although it’s efficacy in weight loss need more investigations, its adverse effects are well established in the literature. In this review, nine studies investigated the effects of ephedra as one of the major components in the combinations with caffeine[9,13,22] or with several other plants[14,20,79,81,83] 5 of which were human studies[9,13,14,20,22]. In one study[13], efficient decreases in body weight and fat were observed with the administration of 210 mg caffeine and 72 mg ephedra per day for 12 wk with an improvement in lipid metabolism and blood pressure without serious adverse effects. In this study, the weight loss at 12-wk was -3.5 ± 0.6 kg with the test compound which was significantly (P < 0.02) higher than that of the placebo. The percentage fat loss shown by DXA was -7.9% ± 2.9% and -1.9% ± 1.1%, respectively (P < 0.05). In another study[20], ephedra at a dose of 40 mg/d and caffeine at a dose of 100 mg/d for a longer time (9 mo) was found to be more efficient than the previous study in lowering body fat and weight, improving lipid metabolism and blood pressure and had no serious adverse effects. The treatment group lost significantly more body weight (-7.18 kg) and body fat (-5.33 kg) than the control group (-2.25 and -0.99 kg, respectively). The difference in data from these two studies possibly resulted from the different dosages and duration of interventions. In a human study[9], a significantly greater weight loss was observed (-4.0 ± 3.4 kg or 3.5% of baseline) in the test group vs (-0.8 ± 2.4 kg or 0.09% of baseline) in the placebo group. Changes were significantly greater for body fat and percentage of body fat in the active group (-3.5 ± 3.3 kg and -2.1% ± 3.0%) in comparison to the placebo group (-0.7 ± 2.9 kg and -0.2% ± 2.3%). The tested product also produced several untoward side effects, leading to some actively treated subjects withdrawing from the study. Additional long-term studies are needed to elucidate the effects of chronic treatment. Thus further examinations in healthy individuals using scientific combinations and dose/duration adjustments are required. Four studies[58,59,65,76] investigated different doses and types of ginseng which is a very popular Chinese herbal medicine. Ginseng significantly decreased weight gain and efficiently improved glucose tolerance[59,76]. It has been reported [58] that hormonal influences can reduce food intake and decrease serum leptin and neuropeptide Y in the brain hypothalamus although not significantly. Thus the anti-obesity effect of this plant requires further investigation. CQ, a succulent vine native to West Africa and Southeast Asia, has been used in traditional African and Ayurvedic medicine for more than a century. Although some studies have examined other uses for CQ, its role in fighting against obesity and for symptoms of July 7, 2009 Volume 15 Number 25 metabolic syndrome has recently attracted interest in other parts of the world, because of its milder adverse effects comparing to ephedra. In this review, two studies focused on this herb [15,26] . CQ in combination with IG[15] induced marked reductions in body weight and fat. In addition, a reduction in waist size of 1.0 cm in the placebo group vs 21.9 cm in the CQ-IG group was observed. As we focused on herbal medicines, all dietary interventions such as the consumption of fruits and vegetables, whole grains, different types of fibers, functional food components including omega three fatty acids or phytochemicals such as flavonoids were omitted. Lifestyle modification is still the safest and efficacious method of inducing a persistent weight loss. In this review, some of the studies were carried out on subjects who simultaneously received diet and exercise programs (mentioned as weight loss programs in Tables). These results demonstrated that specific phytochemical supplements increase the effectiveness of weight loss programs and additional significant anti-obesity effects are observed. Although few studies mentioned adverse effects, it should be noted that many serious adverse events which would have stopped a trial of a pharmaceutical agent would likely not have been identified by the authors’ search methods. Moreover, important safety issues including significant adverse events or supplement-drug interactions relevant to many clinical populations may not be fully addressed by the trials available for review. CONCLUSION Compliance with conventional weight-management programs, which often include increasing energ y expenditure via physical activity, is low. It is not surprising to see the marketing of many new dietary slimming aids aimed at satisfying the need for palatable (as well as safe, effective, and therapeutic) options. In accord with this approach there are numerous investigations on the effectiveness of medicinal plants as natural supplements to reduce body weight. In this paper a variety of herbal supplements had beneficial effects on obesity especially compounds containing ephedra, CQ, ginseng, bitter melon (Momordica charantia), and zingiber. Most of the introduced herbals (Tables 1 and 2) have also been shown to have antioxidant effects, and with regard to the role of oxidative stress in the pathophysiology of some diseases and conditions, their further positive effects may be very promising[86-95]. Attention to these natural compounds and further work on the isolation and characterization of their constituents is highly recommended. REFERENCES 1 2 World Health Organisation. 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