A thermogenic botanical composition containing Citrus aurantifolia fruit rind and Theobroma cacao seed extracts improves body composition in overweight adults: a clinical investigation

Keywords: Body composition, Glucagon-like peptide-1, Resting metabolic rate, Theolim, Thermogenic botanical combination

Abstract

Background and objective: CL19183, or Theolim™, is a novel, proprietary combination of standardized extracts of Citrus aurantifolia fruit rind and Theobroma cacao seeds. Earlier, CL19183 supplementation demonstrated thermogenic activity and weight loss in high-fat diet-induced obese rats. This randomized, double-blind, placebo-controlled, multicenter clinical study (RCT) assessed whether CL19183 supplementation reduced body weight (BW) and improved body composition (BC) in overweight adults.

Methods: The present study recruited 120 overweight male and female subjects (25–55 years) [body mass index (BMI) of 25–29.9 kg/m2] and randomly assigned to receive daily either CL19183 (450 mg; n = 60) or a matched placebo (n = 60) over 16 weeks. The primary efficacy outcome measure was BW reduction in the intention-to-treat (ITT) population. Other efficacy measures included BC using Dual-energy X-ray absorptiometry (DEXA), waist and hip circumferences, resting metabolic rate (RMR) using indirect calorimetry, serum lipid profile, and serum biomarkers utilizing enzyme-linked immunosorbent assay (ELISA). The safety parameters were performed, including complete serum biochemistry, hematology, and urine analysis.

Results: Post-trial, CL19183 supplementation resulted in significant reductions in BW (4.25 ± 1.35 vs. 0.96 ± 1.18 kg; p = 0.0001; CI [confidence interval]: 1.47, 8.59) and BMI (1.57 ± 0.53 vs 0.36 ± 0.46 kg/m2p < 0.0001; CI: 0.87, 2.11), from baseline as compared to placebo. Similarly, total body fat (4.28 ± 1.56 vs. 0.85 ± 1.06 kg; p < 0.0001; CI: 2.35, 7.79) and fat percentage (p < 0.0001) were also reduced from baseline in the CL19183 group vs. placebo. At baseline, after a single dose of CL19183 administration and after 16 weeks, RMR was significantly increased (p < 0.0001 vs. placebo). After 8 and 16 weeks of supplementation, CL19183 significantly increased serum adiponectin and glucagon-like peptide-1 and decreased ghrelin levels vs. baseline and placebo. No major adverse events were reported.

Conclusion: CL19183 supplementation was well-tolerated and led to significant BW reduction and improvements in BC over 16 weeks.

Downloads

Download data is not yet available.

References


1.
Koceva A, Herman R, Janez A, Rakusa M, Jensterle M. Sex- and gender-related differences in obesity: from pathophysiological mechanisms to clinical implications. Int J Mol Sci 2024; 25(13): 7342. doi: 10.3390/ijms25137342

2.
Ohri-Vachaspati P, Leviton L, Bors P, Brennan LK, Brownson RC, Strunk S. Strategies proposed by healthy kids, healthy communities partnerships to prevent childhood obesity. Prev Chronic Dis 2012; 9: E11. doi: 10.5888/pcd9.100292e

3.
Ojulari OV, Lee SG, Nam JO. Beneficial effects of natural bioactive compounds from Hibiscus sabdariffa L. on obesity. Molecules 2019; 24(1): 210. doi: 10.3390/molecules24010210

4.
Hall KD, Sacks G, Chandramohan D, Chow CC, Wang YC, Gortmaker SL, et al. Quantification of the effect of energy imbalance on body weight. Lancet 2011; 378(9793): 826–37. doi: 10.1016/S0140-6736(11)60812-X

5.
Kang JG, Park CY. Anti-obesity drugs: a review about their effects and safety. Diabetes Metab J 2012; 36(1): 13–25. doi: 10.4093/dmj.2012.36.1.13

6.
Williams DM, Nawaz A, Evans M. Drug therapy in obesity: a review of current and emerging treatments. Diabetes Ther 2020; 11(6): 1199–216. doi: 10.1007/s13300-020-00816-y

7.
Heber D. Herbal preparations for obesity: are they useful? Prim Care 2003; 30(2): 441–63. doi: 10.1016/s0095-4543(03)00015-0

8.
Lee YS, Yang WK, Kim HY, Min B, Caturla N, Jones J, et al. Metabolaid® combination of lemon verbena and hibiscus flower extract prevents high-fat diet-induced obesity through AMP-activated protein kinase activation. Nutrients 2018; 10(9): 1204. doi: 10.3390/nu10091204

9.
Apovian CM, Aronne LJ, Bessesen DH, McDonnell ME, Murad MH, Pagotto U, et al. Pharmacological management of obesity: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2015; 100(2): 342–62. doi: 10.1210/jc.2014-3415

10.
Kazemipoor M, Cordell GA, Sarker MM, Radzi CW, Hajifaraji M, En Kiat P. Alternative treatments for weight loss: safety/risks and effectiveness of anti-obesity medicinal plants. Int J Food Properties 2015; 18(9): 1942–63. doi: 10.1080/10942912.2014.933350

11.
Kundimi S, Chinta G, Alluri KV, et al. A synergistic botanical composition increases resting energy expenditure and reduces adiposity in high-fat diet-fed rats. J Am Nutr Assoc 2024; 43(3): 286–95. doi: 10.1080/27697061.2023.2280777

12.
Ammatalli NKR, Kuricheti SSSK, Veeramachaneni S, Koo YK, Ramanathan G, Yalamanchi A. A combination of Citrus aurantifolia fruit rind and Theobroma cacao seed extracts supplementation enhances metabolic rates in overweight subjects: a randomized, placebo-controlled, cross-over study. Food Nutr Res 2024; 68: 10745. doi: 10.29219/fnr.v68.10745

13.
Kou G, Hu Y, Jiang Z, Li Z, Li P, Song H, et al. Citrus aurantium L. polymethoxyflavones promote thermogenesis of brown and white adipose tissue in high-fat diet induced C57BL/6J mice. J Funct Foods 2020; 67: 103860. doi: 10.1016/j.jff.2020.103860
14. Xiong H, Wang J, Ran Q, Lou G, Peng C, Gan Q, et al. Hesperidin: a therapeutic agent for obesity. Drug Des Devel Ther 2019; 13: 3855–66. doi: 10.2147/DDDT.S227499

15.
Tung YC, Chang WT, Li S, Wu JC, Badmeav V, Ho CT, et al. Citrus peel extracts attenuated obesity and modulated gut microbiota in mice with high-fat diet-induced obesity. Food Funct 2018; 9(6): 3363–73. doi: 10.1039/c7fo02066j

16.
Wang X, Li D, Liu F, Cui Y, Li X. Dietary citrus and/or its extracts intake contributed to weight control: evidence from a systematic review and meta-analysis of 13 randomized clinical trials. Phytother Res 2020; 34(8): 2006–22. doi: 10.1002/ptr.6673

17.
Matsui N, Ito R, Nishimura E, Yoshikawa M, Kato M, Kamei M, et al. Ingested cocoa can prevent high-fat diet-induced obesity by regulating the expression of genes for fatty acid metabolism. Nutrition 2005; 21(5): 594–601. doi: 10.1016/j.nut.2004.10.008

18.
Dixit K, Kamath DV, Alluri KV, Davis BA. Efficacy of a novel herbal formulation for weight loss demonstrated in a 16-week randomized, double-blind, placebo-controlled clinical trial with healthy overweight adults. Diabetes Obes Metab 2018; 20(11): 2633–41. doi: 10.1111/dom.13443

19.
Messina C, Albano D, Gitto S, Tofanelli L, Bazzocchi A, Ulivieri FM, et al. Body composition with dual energy X-ray absorptiometry: from basics to new tools. Quant Imaging Med Surg 2020; 10(8): 1687–98. doi: 10.21037/qims.2020.03.02

20.
Atashak S, Peeri M, Jafari A, Azarbayjani MA. Effects of ginger supplementation and resistance training on lipid profiles and body composition in obese men. J Med Plants Res 2011; 5(16): 3827–32. doi: 10.5897/JMPR.9000524

21.
Fullmer S, Benson-Davies S, Earthman CP, Frankenfield DC, Gradwell E, Lee PS, et al. Evidence analysis library review of best practices for performing indirect calorimetry in healthy and non-critically ill individuals. J Acad Nutr Diet 2015; 115(9): 1417–46.e2. doi: 10.1016/j.jand.2015.04.003

22.
De V Weir JB. New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol 1949; 109(1–2): 1–9. doi: 10.1113/jphysiol.1949.sp004363

23.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28(7): 412–19. doi: 10.1007/BF00280883

24.
Shacham S. A shortened version of the profile of mood states. J Pers Assess 1983; 47(3): 305–6. doi: 10.1207/s15327752jpa4703_14

25.
Carmland ME, Kreutzfeldt MD, Holbech JV, Brask-Thomsen PK, Krøigård T, Hansen PN, et al. The effect of lacosamide in peripheral neuropathic paIn: a randomized, double-blind, placebo-controlled, phenotype-stratified trial. Eur J Pain 2024; 28(1): 105–19. doi: 10.1002/ejp.2165

26.
Campbell BI, Colquhoun RJ, Zito G, et al. The effects of a fat loss supplement on resting metabolic rate and hemodynamic variables in resistance trained males: a randomized, double-blind, placebo-controlled, cross-over trial. J Int Soc Sports Nutr 2016; 13: 14. doi: 10.1186/s12970-016-0125-z

27.
Belza A, Frandsen E, Kondrup J. Body fat loss achieved by stimulation of thermogenesis by a combination of bioactive food ingredients: a placebo-controlled, double-blind 8-week intervention in obese subjects. Int J Obes (Lond) 2007; 31(1): 121–30. doi: 10.1038/sj.ijo.0803351

28.
Willoughby D, Hewlings S, Kalman D. Body composition changes in weight loss: strategies and supplementation for maintaining lean body mass, a brief review. Nutrients 2018; 10(12): 1876. doi: 10.3390/nu10121876

29.
Khazem S, Itani L, Kreidieh D, El Masri D, Tannir H, Citarella R, et al. Reduced lean body mass and cardiometabolic diseases in adult males with overweight and obesity: a pilot study. Int J Environ Res Public Health 2018; 15(12): 2754. doi: 10.3390/ijerph15122754

30.
Miller SL, Wolfe RR. The danger of weight loss in the elderly. J Nutr Health Aging 2008; 12(7): 487–91. doi: 10.1007/BF02982710

31.
Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE, Newman AB, et al. Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc 2011; 12(4): 249–56. doi: 10.1016/j.jamda.2011.01.003

32.
McCarthy D, Berg A. Weight loss strategies and the risk of skeletal muscle mass loss. Nutrients 2021; 13(7): 2473. doi: 10.3390/nu13072473

33.
Sudeep HV, Aman K, Jestin TV, Shyamprasad K. Aframomum melegueta seed extract with standardized content of 6-paradol reduces visceral fat and enhances energy expenditure in overweight adults – a randomized double-blind, placebo-controlled clinical study. Drug Des Devel Ther 2022; 16: 3777–91. doi: 10.2147/DDDT.S367350

34.
Campbell WW, Haub MD, Wolfe RR, Ferrando AA, Sullivan DH, Apolzan JW, et al. Resistance training preserves fat-free mass without impacting changes in protein metabolism after weight loss in older women. Obesity (Silver Spring) 2009; 17(7): 1332–9. doi: 10.1038/oby.2009.2

35.
Ryan DH, Deanfield JE, Jacob S. Prioritizing obesity treatment: expanding the role of cardiologists to improve cardiovascular health and outcomes. Cardiovasc Endocrinol Metab 2023; 12(1): e0279. doi: 10.1097/XCE.0000000000000279

36.
Westerterp KR. Control of Energy Expenditure in Humans. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dungan K, Grossman A, Hershman JM, Kaltsas G, McLachlan C, New M, Purnell J, Singer F, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2022.

37.
Ashtary-Larky D, Bagheri R, Abbasnezhad A, Tinsley GM, Alipour M, Wong A. Effects of gradual weight loss v. rapid weight loss on body composition and RMR: a systematic review and meta-analysis. Br J Nutr 2020; 124(11): 1121–32. doi: 10.1017/S000711452000224X

38.
Dubé JJ, Collyer ML, Trant S, Toledo FGS, Goodpaster BH, Kershaw EE, et al. Decreased mitochondrial dynamics is associated with insulin resistance, metabolic rate, and fitness in African Americans. J Clin Endocrinol Metab 2020; 105(4): 1210–20. doi: 10.1210/clinem/dgz272

39.
Zampino M, Semba RD, Adelnia F, Spencer RG, Fishbein KW, Schrack JA, et al. Greater skeletal muscle oxidative capacity is associated with higher resting metabolic rate: results from the Baltimore longitudinal study of aging. J Gerontol A Biol Sci Med Sci 2020; 75(12): 2262–8. doi: 10.1093/gerona/glaa071

40.
Beatty J, Melanson K. Examining changes in respiratory exchange ratio within an 8-week weight loss intervention. J Hum Nutr Diet 2019; 32(6): 737–44. doi: 10.1111/jhn.12664

41.
Dimala CA, Ngu RC, Kadia BM, Tianyi FL, Choukem SP. Markers of adiposity in HIV/AIDS patients: agreement between waist circumference, waist-to-hip ratio, waist-to-height ratio and body mass index. PLoS One 2018; 13(3): e0194653. doi: 10.1371/journal.pone.0194653

42.
Al Hariri M, Al-Sulaiti H, Anwardeen N, Naja K, Elrayess MA. Comparing the metabolic signatures of obesity defined by waist circumference, waist-hip ratio, or BMI. Obesity (Silver Spring) 2024; 32(8): 1494–507. doi: 10.1002/oby.24070

43.
Ramírez-Manent JI, Jover AM, Martinez CS, Tomás-Gil P, Martí-Lliteras P, López-González ÁA. Waist circumference is an essential factor in predicting insulin resistance and early detection of metabolic syndrome in adults. Nutrients 2023; 15(2): 257. doi: 10.3390/nu15020257

44.
Zhang T, Chen J, Tang X, Luo Q, Xu D, Yu B. Interaction between adipocytes and high-density lipoprotein:new insights into the mechanism of obesity-induced dyslipidemia and atherosclerosis. Lipids Health Dis 2019; 18(1): 223. doi: 10.1186/s12944-019-1170-9

45.
Battineni G, Sagaro GG, Chintalapudi N, Amenta F, Tomassoni D, Tayebati SK. Impact of obesity-induced inflammation on cardiovascular diseases (CVD). Int J Mol Sci 2021; 22(9): 4798. doi: 10.3390/ijms22094798

46.
Abdesselam A, Zidoum H, Zadjali F, Hedjam R, Al-Ansari A, Bayoumi R, et al. Estimate of the HOMA-IR cut-off value for identifying subjects at risk of insulin resistance using a machine learning approach. Sultan Qaboos Univ Med J 2021; 21(4): 604–12. doi: 10.18295/squmj.4.2021.030
47. Vladu IM, Forțofoiu M, Clenciu D, Forțofoiu MC, Pădureanu R, Radu L, et al. Insulin resistance quantified by the value of HOMA-IR and cardiovascular risk in patients with type 2 diabetes. Exp Ther Med 2022; 23(1): 73. doi: 10.3892/etm.2021.10996

48.
Kim S, Song K, Lee M, Suh J, Chae HW, Kim H-S, et al. Trends in HOMA-IR values among South Korean adolescents from 2007–2010 to 2019–2020: a sex-, age-, and weight status-specific analysis. Int J Obes (Lond) 2023; 47(9): 865–72. doi: 10.1038/s41366-023-01340-2

49.
Achari AE, Jain SK. Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction. Int J Mol Sci 2017; 18(6): 1321. doi: 10.3390/ijms18061321

50.
Yamauchi T, Iwabu M, Okada-Iwabu M, Kadowaki T. Adiponectin receptors: a review of their structure, function and how they work. Best Pract Res Clin Endocrinol Metab 2014; 28(1): 15–23. doi: 10.1016/j.beem.2013.09.003

51.
Li H, Kim UH, Yoon JH, Ji HS, Park HM, Park HY, et al. Suppression of hyperglycemia and hepatic steatosis by black-soybean-leaf extract via enhanced adiponectin-receptor signaling and AMPK activation. J Agric Food Chem 2019; 67(1): 90–101. doi: 10.1021/acs.jafc.8b04527

52.
Hui X, Gu P, Zhang J, Nie T, Pan Y, Wu D, et al. Adiponectin enhances cold-induced browning of subcutaneous adipose tissue via promoting M2 macrophage proliferation. Cell Metab 2015; 22(2): 279–90. doi: 10.1016/j.cmet.2015.06.004

53.
Sovetkina A, Nadir R, Fung JNM, Nadjarpour A, Beddoe B. The physiological role of ghrelin in the regulation of energy and glucose homeostasis. Cureus 2020; 12(5): e7941. doi: 10.7759/cureus.7941

54.
Tong Y, Xu S, Huang L, Chen C. Obesity and insulin resistance: pathophysiology and treatment. Drug Discov Today 2022; 27(3): 822–30. doi: 10.1016/j.drudis.2021.11.001
55. Popoviciu MS, Păduraru L, Yahya G, Metwally K, Cavalu S. Emerging role of GLP-1 agonists in obesity: a comprehensive review of randomised controlled trials. Int J Mol Sci 2023; 24(13): 10449. doi: 10.3390/ijms241310449

56.
D’Alessio DA, Kahn SE. The development of glucagon-like peptide 1 as a therapeutic: the triumph of the lasker award for obesity is a victory for diabetes research. Diabetes Care 2025; 48(1): 3–5. doi: 10.2337/dci24-0092

57.
Beiroa D, Imbernon M, Gallego R, Senra A, Herranz D, Villarroya F, et al. GLP-1 agonism stimulates brown adipose tissue thermogenesis and browning through hypothalamic AMPK. Diabetes 2014; 63(10): 3346–58. doi: 10.2337/db14-0302

58.
Oliveira FCB, Bauer EJ, Ribeiro CM, Pereira SA, Beserra BTS, Wajner SM, et al. Liraglutide activates type 2 deiodinase and enhances b3- adrenergic-induced thermogenesis in mouse adipose tissue. Front Endocrinol 2022; 12: 803363. doi: 10.3389/fendo.2021.803363

59.
Hropot T, Herman R, Janez A, Lezaic L, Jensterle M. Brown adipose tissue: a new potential target for glucagon-like peptide 1 receptor agonists in the treatment of obesity. Int J Mol Sci 2023; 24: 8592. doi: 10.3390/ijms24108592
Published
2025-06-24
How to Cite
Chaladavada , A., Koo , Y. K., Kim , S., Veeramachaneni , S., Ramanathan , G., & Yalamanchi , A. (2025). A thermogenic botanical composition containing <em>Citrus aurantifolia</em> fruit rind and <em>Theobroma cacao</em&gt; seed extracts improves body composition in overweight adults: a clinical investigation. Food & Nutrition Research, 69. https://doi.org/10.29219/fnr.v69.12159
Section
Original Articles