Antihyperlipidemic Effects of Stevia rebaudiana Bertoni: A Review Tropical Journal of Natural Product Research
Article Sidebar
Main Article Content
Abstract
Stevia rebaudiana, a natural sweetener, has attracted significant attention for its potential antihyperlipidemic effects. This review aims to assess the effectiveness of Stevia in managing hyperlipidaemia with special emphasis on its effect on total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels. A literature review of multiple studies was conducted to explore the antihyperlipidemic properties of Stevia. The findings indicated that Stevia possesses significant antihyperlipidemic properties, largely due to its substantial amount of steviol glycosides, such as stevioside, and rebaudioside A. Studies have shown that Stevia consumption significantly reduces TC, TG, and LDL levels while maintaining or potentially increasing HDL levels. Stevia inhibits the activity of HMG-CoA reductase, leading to reduced cholesterol synthesis in Hep-G2 cells, enhances cholesterol internalization, and also promotes cholesterol storage in lipid droplets. Moreover, it upregulates bile acid excretion and prevents bile acids from being reabsorbed in the small intestine, further lowering cholesterol levels. Furthermore, the expression of adipogenic transcription factors and lipogenic genes are also down-regulated, resulting in decreased lipid accumulation and triglyceride contents. Although, initial results are promising, more in-depth clinical investigations are essential to determine the long-term efficacy and safety of Stevia as an antihyperlipidemic agent. These studies would need to consider various dosages, treatment durations, and individual differences regarding Stevia consumption.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
1. Shattat GF. A review article on hyperlipidemia: Types, treatments and new drug targets. Biomed Pharmacol J. 2014; 7(2):399–409.
2. Asija R, Singh C, Hemlata. A Comprehensive Review on Antihyperlipidemic Activity of Various Medicinal Plants. Int J Curr Pharm Rev Res. 2016; 7(6):405–415.
3. Yao YS, Li T Di, Zeng ZH. Mechanisms underlying direct actions of hyperlipidemia on myocardium: An updated review. Lipids Health Dis. 2020; 19(1):23.
4. Mumthaj P, Natarajan P, Janani A., Vijay J, Gokul V. A Global Review Article on Hyperlipidemia. Int J Pharm Sci Rev Res. 2021; 68(1):104–110.
5. World Health Organization. Noncommunicable diseases: risk factors. The Global Health Observatory [Internet]. 2021 [cited 2024 May 25]. Available from: https://www.who.int/data/gho/data/themes/topics/topic-details/GHO/ncd-risk-factors
6. Ahmad U, Ahmad RS, Arshad MS, Mushtaq Z, Hussain SM, Hameed A. Antihyperlipidemic efficacy of aqueous extract of Stevia rebaudiana Bertoni in albino rats. Lipids Health Dis. 2018; 17(1):175.
7. Karr S. Epidemiology and management of hyperlipidemia. Am J Manag Care. 2017; 23(9 Suppl):S139–S148.
8. Zodda D, Giammona R, Schifilliti S. Treatment Strategy for Dyslipidemia in Cardiovascular Disease Prevention: Focus on Old and New Drugs. Pharm. 2018; 6(1):10.
9. Giuffré L, Romaniuk R, Ciarlo E. Stevia, Ka’aHe’e, wild sweet herb from South America - An overview. Emirates J Food Agric. 2013; 25(10):746–750.
10. Peteliuk V, Rybchuk L, Bayliak M, Storey KB, Lushchak O. Natural sweetener stevia rebaudiana: Functionalities, health benefits and potential risks. EXCLI J. 2021; 20:1412–1430.
11. Sharma N, Mogra R, Upadhyay B. Effect of stevia extract intervention on lipid profile. Stud Ethno-Medicine. 2009; 3(2):137–140.
12. Hossain MS, Alam MB, Asadujjaman M, Islam MM, Rahman MA, Islam MA, Islam A. Antihyperglycemic and Antihyperlipidemic Effects of Different Fractions of Stevia rebaudiana Leaves in Alloxan Induced Diabetic Rats. Int J Pharm Pharm Sci. 2011; 2(7):1722–1729.
13. Singh S, Garg V, Yadav D. Antihyperglycemic and antioxidative ability of Stevia rebaudiana (Bertoni) leaves in diabetes induced mice. Int J Pharm Pharm Sci. 2013; 5(Suppl 2):297–302.
14. Latarissa IR, Barliana MI, Lestari K. A comprehensive review of Stevia rebaudiana Bertoni effects on human health and its mechanism. J Adv Pharm Educ Res. 2020; 10(2):91–95.
15. Gupta E, Purwar S, Sundaram S, Rai GK. Nutritional and therapeutic values of Stevia rebaudiana: A review. J Med Plants Res. 2013; 7(46):3343–3353.
16. Pandey S. Morphology, Chemical Composition and Therapeutic Potential of Stevia Rebaudiana. Indo Am J Pharm Sci. 2018; 05(04):2260–2266.
17. Carrera-Lanestosa A, Moguel-Ordóñez Y, Segura-Campos M. Stevia rebaudiana Bertoni: A Natural Alternative for Treating Diseases Associated with Metabolic Syndrome. J Med Food. 2017; 20(10):933–943.
18. Chatsudthipong V and Muanprasat C. Stevioside and related compounds: Therapeutic benefits beyond sweetness. Pharmacol Ther. 2009; 121(1):41–54.
19. Gaweł-Bȩben K, Bujak T, Nizioł-Łukaszewska Z, Antosiewicz B, Jakubczyk A, Karaś M, Rybczyńska K. Stevia rebaudiana Bert. leaf extracts as a multifunctional source of natural antioxidants. Molecules. 2015; 20(4):5468–5486.
20. Chen J, Xia Y, Sui X, Peng Q, Zhang T, Li J, Zhang J. Steviol, a natural product inhibits proliferation of the gastrointestinal cancer cells intensively. Oncotarget. 2018; 9(41):26299–26308.
21. Singh DP, Kumari M, Prakash HG, Rao GP, Solomon S. Phytochemical and Pharmacological Importance of Stevia: A Calorie-Free Natural Sweetener. Sugar Tech. 2019; 21(2):227–234.
22. Kim IS, Yang M, Lee OH, Kang SN. The antioxidant activity and the bioactive compound content of Stevia rebaudiana water extracts. Lwt - Food Sci Technol. 2011; 44(5):1328–1332.
23. Sunitha V, Irene J, M RA. Biochemical and Phytochemical Activity of Stevia Rebaudiana by Using Ethanol Extract. World J Pharm Sci. 2015 ;3(10):2077–2080.
24. Mali AB, Joshi M, Kulkarni V. Phytochemical Screening and Antimicrobial Activity of Stevia rebaudiana Leaves. Int J Curr Microbiol Appl Sci. 2015; 4(10):678–685.
25. Borgo J, Laurella LC, Martini F, Catalán CAN, Sülsen VP. Stevia genus: Phytochemistry and biological activities update. Molecules. 2021; 26(9):2733.
26. Chouhan ES, Srivastava S, Chawla P. Proximate and Phytochemical Analysis of Stevia. Int Ayuv Med J. 2016; 4(8):2476–2481.
27. Howlader MMS, Ahmed SR, Kubra K, Bhuiyan MKH. Biochemical and phytochemical evaluation of Stevia rebaudiana. Asian J Med Biol Res. 2016; 2(1):121–130.
28. Ahsan F, Bashir S, Shah F ul H. Nutritional and Medicinal Properties of Stevia rebaudiana. Curr Res Diabetes Obes J. 2020; 13(4):47–53.
29. Midmore DJ and Rank AH. A new rural industry-Stevia- to replace imported chemical sweeteners. A report for the Rural Industries Research and Development Corporation [Internet]. Rural Industries Research & Corporation Web Publication. 2002. Available from: https://agrifutures.com.au/wp-content/uploads/publications/W02-022.pdf
30. Ilias AN, Hamzah H, Ismail IS, Ajat M. Stevia: Limiting cholesterol synthesis in hep-G2 cells. Asia-Pacific J Mol Biol Biotechnol. 2020; 28(1):110–119.
31. Ilias AN, Ismail IS, Hamzah H, Mohidin TBM, Idris MF, Ajat M. Rebaudioside A Enhances LDL Cholesterol Uptake in HepG2 Cells via Suppression of HMGCR Expression. Reports Biochem Mol Biol. 2021; 10(3):401–411.
32. Tirawanchai N, Homongkol P, Chansriniyom C, Somkasetrin A, Jantaravinid J, Kengkoom K, Ampawong S. Lipid-lowering effect of Phyllanthus embilica and Alpinia galanga extracts on HepG2 cell line. Pharm Nutr. 2019; 9:100153.
33. Hou Y, Wang P, Liu J, Liu A, Peng X, Wang L, Zhang J. Study of the Extraction and Hypolipidemic Mechanism of Steviosides from Stevia rebaudiana Leaves. Adv J Food Sci Technol. 2016; 12(8):451–456.
34. Akbarzadeh S, Eskandari F, Tangestani H, Bagherinejad ST, Bargahi A, Bazzi P, Daneshi A, Sahrapoor A, O’Connor WJ, Rahbar AR. The Effect of Stevia rebaudiana on Serum Omentin and Visfatin Level in STZ-Induced Diabetic Rats. J Diet Suppl. 2015; 12(1):11–22.
35. Kurek JM, Zielińska-Wasielica J, Kowalska K, Krejpcio Z, Olejnik A. Modulating effects of steviol and steviol glycosides on adipogenesis, lipogenesis, glucose uptake and insulin resistance in 3T3-L1 adipocyte model. J Funct Foods. 2022; 94:105141.
36. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith Jr SC, Sperling L, Virani SS, Yeboah J. Guideline on the Management of Blood Cholesterol. J Am Coll Cardiol. 2018; 73(24):e285–350.
37. Abo Elnaga NIE, Massoud MI, Yousef MI, Mohamed HHA. Effect of stevia sweetener consumption as non-caloric sweetening on body weight gain and biochemical’s parameters in overweight female rats. Ann Agric Sci. 2016; 61(1):155–163.
38. Scaria A, Kamath JV, Chakraborty M. Anti Hyperglycemic, Anti Oxidant, Anti Hyperlipidemic & Nephroprotective Effect of Stevioside in Diabetic Rats. Int J Ayurv Med. 2017; 8(4):169–173.
39. Abdel-Aal RA, Abdel-Rahman MS, Bayoumi S Al, Ali LA. Effect of stevia aqueous extract on the antidiabetic activity of saxagliptin in diabetic rats. J Ethnopharmacol. 2021; 265:113188.
40. Kurek JM, Król E, Krejpcio Z. Steviol glycosides supplementation affects lipid metabolism in high-fat fed STZ-induced diabetic rats. Nutrients. 2021; 13(1):112.
41. Suryadinata ER, Djuang MH, Novriani E, Merry A. Test of Stevia Leaf Ethanol Extract (Stevia Rebaudiana) Administered Orally to Female Wistar Rats (Rattus norvegicus) on a High-Fat Diet to Prevent Dyslipidemia. J Edu Health. 2023; 14(04):149–157.
42. Aissaoui O, Terki L, Ameur SA, Bitam A. In vivo evaluation of antioxydant potential and antihyperglycemic effect of Stevia rebaudiana Bertoni. Agron Res. 2024; 22(1):33–51.
43. Aghajanyan A, Movsisyan Z, Trchounian A. Antihyperglycemic and Antihyperlipidemic Activity of Hydroponic Stevia rebaudiana Aqueous Extract in Hyperglycemia Induced by Immobilization Stress in Rabbits. Biomed Res Int. 2017; 2017:9251358.
44. Kosmas CE, Pantou D, Sourlas A, Papakonstantinou EJ, Uceta RE, Guzman E. New and emerging lipid-modifying drugs to lower LDL cholesterol. Drugs Context. 2021; 10:1–22.
45. Uddin MA, Akter F, Chowdhury IH, Asha UH, Tanny SZ, Sony TA, Neon N, Saha N, Sikder M, Yesmine S. Toxicological Studies of Leaf extract of Stevia rebaudiana Bertoni in Sprague-Dawley Rats. Trop J Nat Prod Res. 2022; 6(5):714–720.
46. Ritu M, Nandini J. Nutritional composition of Stevia rebaudiana, a sweet herb, and its hypoglycaemic and hypolipidaemic effect on patients with non-insulin dependent diabetes mellitus. J Sci Food Agric. 2016; 96(12):4231–4234.
47. Holvoet P, Rull A, García-Heredia A, López-Sanromà S, Geeraert B, Joven J, Camps J. Stevia-derived compounds attenuate the toxic effects of ectopic lipid accumulation in the liver of obese mice: A transcriptomic and metabolomic study. Food Chem Toxicol. 2015; 77:22–33.
48. Rotimi SO, Rotimi OA, Adelani IB, Onuzulu C, Obi P, Okungbaye R. Stevioside modulates oxidative damage in the liver and kidney of high fat/low streptozocin diabetic rats. Heliyon. 2018; 4(5):e00640.
49. Kamal NH, Essmat A, El Askary HI, El Hefnawy HM, Wahab SMA, Meselhy MR. Chemical profile and beneficial effect of standardized extract of Stevia rebaudiana Bertoni leaves on metabolic syndrome in high fat diet streptozotocin-induced diabetic rats. Appl Biol Chem. 2022; 65(55):1–13.
50. Ameer K, Jiang GH, Amir RM, Eun JB. Antioxidant potential of Stevia rebaudiana(Bertoni). Pathology: Oxidative Stress and Dietary Antioxidants. Academic Press Incorporated; 2020. 345–356 p.
51. Galindo M del RP, Housni FE, Martinez-Moreno AG, Castillo ZR, Villalvazo AC, Saenz-Pardo-Reyes E. Effect of stevia and fructose consumption on food intake, body weight gain and metabolic parameters in rat. Indian J AnimReseacrh. 2019; 10:1–4.
52. Bagiana IK, Puspitaningrum I, Kusmita L, Franyoto YD, Mutmainah. Anti-hypercholesterol effects of microencapsulation of leaf extract Stevia rebaudiana. Int J Front Chem Pharm Res. 2022; 2(1):001–006.
53. Chen J and Li X. Hypolipidemic effect of flavonoids from mulberry leaves in triton WR-1339 induced hyperlipidemic mice. Asia Pac J Clin Nutr. 2007; 16(Suppl 1):290–294.
54. Kalaiselvi M. Anti - Hyperglycemic Effects on Stevia rebaudiana on Alloxan Induced Diabetic Rats. Int J Pharm Drug Anal. 2017; 5(8):347–353.
55. Assaei R, Mokarram P, Dastghaib S, Darbandi S, Darbandi M, Zal F, Akmali M, Ranjbar Omrani GH. Hypoglycemic effect of aquatic extract of Stevia in pancreas of diabetic rats: PPARγ-dependent regulation or antioxidant potential. Avicenna J Med Biotechnol. 2016; 8(2):65–74.
56. Jeppesen PB, Gregersen S, Poulsen CR, Hermansen K. Stevioside acts directly on pancreatic β cells to secrete insulin: Actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity. Metabol. 2000; 49(2):208–214.
57. Philippaert K, Pironet A, Mesuere M, Sones W, Vermeiren L, Kerselaers S, Pinto S, Segal A, Antoine N, Gysemans C, Laureys J, Lemaire K, Gilon P, Cuypers E, Tytgat J, Mathieu C, Schuit F, Rorsman P, Talavera K, Voets T, Vennekens R. Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. Nat Commun. 2017; 8:14733.
58. Ahmad U and Ahmad RS. Anti diabetic property of aqueous extract of Stevia rebaudiana Bertoni leaves in Streptozotocin-induced diabetes in albino rats. BMC Complement Altern Med. 2018; 18:179.
59. Melis MS and Sainati AR. Effect of calcium and verapamil on renal function of rats during treatment with stevioside. J Ethnopharmacol. 1991; 33(3):257–262.
60. Melis MS and Sainati AR. Participation of prostaglandins in the effect of stevioside on rat renal function and erterial pressure. Braz J Med Biol Res. 1991; 24(12):1269–1276.
61. Chan P, Xu DY, Liu JC, Chen YJ, Tomlinson B, Huang WP, Cheng JT. The effect of stevioside on blood pressure and plasma catecholamines in spontaneously hypertensive rats. Life Sci. 1998; 63(19):1679–1684.
62. Chan P, Tomlinson B, Chen YJ, Liu JC, Hsieh MH, Cheng JT. A double-blind placebo-controlled study of the effectiveness and tolerability of oral stevioside in human hypertension. Br J Clin Pharmacol. 2000; 50(3):215–220.
63. Hsieh MH, Chan P, Sue YM, Liu JC, Liang TH, Huang TY, Tomlinson B, Chow MSS, Kao PF, Chen YJ. Efficacy and Tolerability of Oral Stevioside in Patients with Mild Essential Hypertension: A Two-Year, Randomized, Placebo-Controlled Study. Clin Ther. 2003; 25(11):2797–2808.
64. Chang JC, Wu M., Liu IM, Cheng JT. Increase of Insulin Sensitivity by Stevioside in Fructose-rich Chow-fed Rats. Horm Metab Res. 2005; 37:610–616.
65. Farhat G, Berset V, Moore L. Effects of stevia extract on postprandial glucose response, satiety and energy intake: A three-arm crossover trial. Nutrients. 2019; 11:3036.
66. Prata C, Zambonin L, Rizzo B, Maraldi T, Angeloni C, Dalla Sega FV, Fiorentini D, Hrelia S. Glycosides from Stevia rebaudiana Bertoni possess insulin-mimetic and antioxidant activities in rat cardiac fibroblasts. Oxid Med Cell Longev. 2017; 2017:3724545.
67. Sánchez-Aceves LM, Dublán-García O, López-Martínez LX, Novoa-Luna KA, Islas-Flores H, Galar-Martínez M, García-Medina S, Hernández-Navarro MD, Gómez-Oliván LM. Reduction of the Oxidative Stress Status Using Steviol Glycosides in a Fish Model (Cyprinus carpio). Biomed Res Int. 2017; 2017:2352594.
68. Chaiyana W, Charoensup W, Sriyab S, Punyoyai C, Neimkhum W. Herbal Extracts as Potential Antioxidant, Anti aging, Anti inflammatory and Whitening Cosmeceutical Ingredients. Chem Biodivers. 2021; 18(7):e2100245.
69. Hayet S, Sujan KM, Mustari A, Miah MA. Antimicrobial activity of Stevia rebaudiana against antibiotic resistant ESBL producing uropathogens and evaluation of its antioxidant activity. Int J Adv Res Biol Sci. 2017; 4(3):110–118.
70. Wang T, Guo M, Song X, Zhang Z, Jiang H, Wang W, Fu Y, Cao Y, Zhu L, Zhang N. Stevioside Plays an Anti-inflammatory Role by Regulating the NF-κB and MAP
Pathways in S. aureus-infected Mouse Mammary Glands. Inflamm. 2014; 37(5):1837–1846.
71. Mostafa AF, Elalfy MM, Shata A, Elhadidy MG. Prophylactic effect of aquatic extract of stevia on acetic acid induced-ulcerative colitis in male rats: A possible role of Nrf2 and PPARγ. J Basic Clin Physiol Pharmacol. 2021; 32(6):1093–1104.
72. Iatridis N, Kougioumtzi A, Vlataki K, Papadaki S, Magklara A. Anti-Cancer Properties of Stevia rebaudiana; More than a Sweetener. Molecules. 2022; 27(4):1362.
73. Gupta E, Kaushik S, Sharma R, Balapure AK, Sundaram S. Anticancer Potential of Steviol in MCF-7 Human Breast Cancer Cells. Pharmacogn Mag. 2017; 13(51):345–350.
74. Mariana MA, Maricruz OA, Marta LS, Ivonne PX, Ada MRC, Sandra LCH. Antibacterial activity of extracts of Stevia rebaudiana Bertoni against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa. J Med Plants Res. 2017; 11(25):414–418.
75. Brambilla E, Cagetti MG, Ionescu A, Campus G, Lingström P. An in vitro and in vivo comparison of the effect of Stevia rebaudiana extracts on different caries-related variables: A randomized controlled trial pilot study. Caries Res. 2014; 48(1):19–23.
76. Usha C, Ramarao S, John BM, Babu ME. Anticariogenicity of Stevia rebaudiana extract when used as a mouthwash in high caries risk patients: Randomized controlled clinical trial. World J Dent. 2017; 8(5):364–369.
77. Takahashi K, Matsuda M, Ohashi K, Taniguchi K, Nakagomi O, Abe Y, Mori S, Sato N, Okutani K, Shigeta S. Analysis of anti-rotavirus activity of extract from Stevia rebaudiana. Antiviral Res. 2001; 49(1):15–24.
78. Ceole LF, Companhoni MVP, Lopes SMS, Oliveira AJB de, Gonçalves RAC, Filho BPD, Nakamura CV, Ueda-Nakamura T. Anti-herpes activity of polysaccharide fractions from Stevia rebaudiana leaves. Nat Prod Res. 2018; 34(11):1558–1562.
79. Ramos-Tovar E, Hernández-Aquino E, Casas-Grajales S, Buendia-Montaño LD, Galindo-Gómez S, Camacho J, Tsutsumi V, Muriel P. Stevia prevents acute and chronic liver injury induced by carbon tetrachloride by blocking oxidative stress through Nrf2 upregulation. Oxid Med Cell Longev. 2018; 2018:3823426.
80. Ramos-Tovar E, Buendia-Montaño LD, Galindo-Gómez S, Hernández-Aquino E, Tsutsumi V, Muriel P. Stevia prevents experimental cirrhosis by reducing hepatic myofibroblasts and modulating molecular profibrotic pathways. Hepatol Res. 2019; 49(2):212–223.
81. Rizwan F, Yesmine S, Banu SG, Chowdhury IA, Hasan R, Chatterjee TK. Renoprotective effects of stevia (Stevia rebaudiana Bertoni), amlodipine, valsartan, and losartan in gentamycin-induced nephrotoxicity in the rat model: Biochemical, hematological and histological approaches. Toxicol Rep. 2019; 6:683–691.
82. Rizwan F, Rashid HU, Yesmine S, Monjur F, Chatterjee TK. Preliminary analysis of the effect of Stevia (Stevia rebaudiana) in patients with chronic kidney disease (stage I to stage III). Contemp Clin Trials Commun. 2018; 12:17–25.