The rising global burden of metabolic disorders has driven increased consumption of non-nutritive sweeteners like stevia as sugar substitutes. While purified steviol glycosides are generally recognised as safe, commercially available stevia products often contain multiple additional ingredients whose combined effects remain inadequately characterised. This study evaluated the subchronic effects of a commercial stevia sweetener on haematological and metabolic parameters in healthy male Wistar rats. Fifteen (15) adult male Wistar (180-200 g) rats were randomly assigned to three groups (n=5 per group): control (distilled water), low-dose stevia (200 mg/kg), and high-dose stevia (400 mg/kg). Treatments were administered daily by oral gavage for eight weeks. Haematological parameters were analysed using an automated haematology analyser, while lipid profile, fasting blood glucose, and insulin were measured spectrophotometrically using standard kits. Stevia supplementation significantly reduced packed cell volume at both doses (p<0.05). The 400 mg/kg dose increased total white blood cell count and reduced platelet count (p<0.05). Monocyte and eosinophil percentages increased at 400 mg/kg and 200 mg/kg, respectively (p<0.05). Metabolically, both doses significantly reduced insulin levels and HOMA-IR values while paradoxically elevating fasting blood glucose (p<0.05). The 400 mg/kg dose significantly increased total cholesterol, triglycerides, and low-density lipoproteins (p<0.05). Evidence from the present study has shown that subchronic commercial stevia supplementation improved insulin sensitivity in healthy rats but concurrently induced haematological and metabolic stress, manifesting as reduced packed cell volume, leukocytosis, hyperglycaemia, and dyslipidaemia. These findings underscore the critical influence of dose and duration context and highlight the need for stevia-based products formulated with fewer potentially harmful additives. The dissociation between improved insulin sensitivity and worsened metabolic control suggests that multiple ingredients may exert opposing effects, warranting further investigation into commercial formulations rather than assuming equivalence to purified steviol glycosides.
| Published in | Journal of Food and Nutrition Sciences (Volume 14, Issue 2) |
| DOI | 10.11648/j.jfns.20261402.17 |
| Page(s) | 162-169 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2026. Published by Science Publishing Group |
Stevia, Stevia Glycosides, Haematological Parameters, Lipid Profile, Blood Sugar, Insulin
Parameters | Control n=5 | 200 mg/kg Stevia n=5 | 400 mg/kg Stevia n=5 |
|---|---|---|---|
Red blood cell count (x1012/L) | 7.80±0.22 | 7.38±0.39 | 7.08±0.34 |
Haemoglobin conc. (g/dI) | 14.14±0.26 | 13.70±0.68 | 13.08±0.18 |
Packed cell volume (%) | 45.00±0.55 | 40.20±1.46* | 39.40±0.68* |
Total white blood cell count (x109/L) | 11.32±1.20 | 11.44±2.88 | 15.08±0.86* |
Neutrophil (%) | 12.60±5.47 | 10.80±5.45 | 10.80±1.80 |
Lymphocytes (%) | 83.60±5.56 | 83.80±7.06 | 83.80±1.80 |
Monocyte (%) | 2.80±0.20 | 3.60±1.33 | 3.80*±0.37 |
Eosinophil (%) | 1.00±0.00 | 1.80±0.37* | 1.60±0.24 |
Platelet (x109/L) | 836.80±31.99 | 780.00±15.84 | 550.79±138.82* |
Parameters | Control n=5 | 200 mg/kg Stevia n=5 | 400 mg/kg Stevia n=5 |
|---|---|---|---|
Total Cholesterol (mmol/L) | 2.92±0.17 | 3.10±0.12 | 3.38±0.10* |
Triglycerides (mmol/L) | 1.15±0.06 | 1.18±0.05 | 1.32±0.02* |
High-Density Lipoprotein (mmol/L) | 1.22±0.06 | 1.28±0.04 | 1.31±0.03 |
Low-Density Lipoprotein (mmol/L) | 1.18±0.11 | 1.29±0.05 | 1.37±0.08* |
Fasting Blood Sugar (mmol/L) | 3.64±0.19 | 4.70±0.19* | 5.02±0.29* |
HOMA-IR | 0.38±0.02 | 0.32±0.02* | 0.31±0.01* |
Insulin (µU/mL) | 2.37±0.02 | 1.53±0.05* | 1.40±0.01* |
HOMA-IR | Homeostatic Model Assessment for Insulin Resistance |
TC | Total Cholesterol |
HDL | High-density Lipoprotein |
LDL | Low-density Lipoprotein |
TG | Triglycerides |
ANOVA | Analysis of Variance |
SEM | Standard Error of the Mean |
PCV | Packed Cell Volume |
CPIR | Cephalic Phase Insulin Release |
STZ | Streptozotocin |
| [1] | Hong Q-Y, Huang Y, Yang J, Su L-T, Dai Z-R, Zhao C-F. Food sweeteners: Angels or clowns for human health? Current Research in Food Science. 2025; 10: 101032. |
| [2] | Pearlman M, Obert J, Casey L. The Association Between Artificial Sweeteners and Obesity. Current Gastroenterology Reports. 2017; 19(12): 64. |
| [3] | Lemus-Mondaca R, Vega-Gálvez A, Zura-Bravo L, Ah-Hen K. Stevia rebaudiana Bertoni, source of a high-potency natural sweetener: A comprehensive review on the biochemical, nutritional and functional aspects. Food Chemistry. 2012; 132(3): 1121-32. |
| [4] | Masoumi SJ, Ranjbar S, Keshavarz V. The effectiveness of stevia in diabetes mellitus: A review. International journal of nutrition sciences. 2020; 5(2): 45-9. |
| [5] | Ahmad J, Khan I, Blundell R, Azzopardi J, Mahomoodally MF. Stevia rebaudiana Bertoni.: an updated review of its health benefits, industrial applications and safety. Trends in Food Science & Technology. 2020; 100: 177-89. |
| [6] | Schiatti-Sisó IP, Quintana SE, García-Zapateiro LA. Stevia (Stevia rebaudiana) as a common sugar substitute and its application in food matrices: an updated review. J Food Sci Technol. 2023; 60(5): 1483-92. |
| [7] | Purkayastha S, Markosyan A, Prakash I, Bhusari S, Pugh Jr G, Lynch B, Roberts A. Steviol glycosides in purified stevia leaf extract sharing the same metabolic fate. Regulatory Toxicology and Pharmacology. 2016; 77: 125-33. |
| [8] | Gasmalla MA, A, Yang R, Hua X. Stevia rebaudiana Bertoni: An alternative sugar replacer and its application in food industry. Food Engineering Reviews. 2014; 6(4): 150-62. |
| [9] | Renwick AG, Tarka SM. Microbial hydrolysis of steviol glycosides. Food Chem Toxicol. 2008; 46 Suppl 7: S70-4. |
| [10] | Goyal SK, Samsher, Goyal RK. Stevia (Stevia rebaudiana) a bio-sweetener: a review. International journal of food sciences and nutrition. 2010; 61(1): 1-10. |
| [11] | Wang L, Chang T, Zhu T, Hu W, Wang X, Dong C, et al. Stevia rebaudiana Bertoni as a sweet herbal medicine: traditional uses, potential applications, and future development. Front Pharmacol. 2025; 16: 1638147. |
| [12] | Kujawska M, Schmeda-Hirschmann G. The use of medicinal plants by Paraguayan migrants in the Atlantic Forest of Misiones, Argentina, is based on Guarani tradition, colonial and current plant knowledge. Journal of Ethnopharmacology. 2022; 283: 114702. |
| [13] | BeMiller JN. 19 - Carbohydrate and Noncarbohydrate Sweeteners. In: BeMiller JN, ed. Carbohydrate Chemistry for Food Scientists (Third Edition): AACC International Press; 2019: 371-99. |
| [14] | Samuel P, Ayoob KT, Magnuson BA, Wölwer-Rieck U, Jeppesen PB, Rogers PJ, et al. Stevia Leaf to Stevia Sweetener: Exploring Its Science, Benefits, and Future Potential. The Journal of Nutrition. 2018; 148(7): 1186S-205S. |
| [15] | Majid H, Masood Q, Khan AH. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR): A Better Marker for Evaluating Insulin Resistance Than Fasting Insulin in Women with Polycystic Ovarian Syndrome. J Coll Physicians Surg Pak. 2017; 27(3): 123-6. |
| [16] | Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab. 2008; 294(1): E15-26. |
| [17] | Díaz L, Zambrano E, Flores ME, Contreras M, Crispín JC, Alemán G, et al. Ethical considerations in animal research: the principle of 3R's. Revista de investigacion clinica. 2021; 73(4): 199-209. |
| [18] | Kiani AK, Pheby D, Henehan G, Brown R, Sieving P, Sykora P, et al. Ethical considerations regarding animal experimentation. Journal of preventive medicine and hygiene. 2022; 63(2 Suppl 3): E255. |
| [19] | Kobylewski S. Toxicology of rebaudioside A: a review. Department of Environmental Health Sciences and Molecular Toxicology, UCLA School of Public Health Los Angeles, California. 2008. |
| [20] | Schierbauer J, Sanfilippo S, Grothoff A, Fehr U, Wachsmuth N, Voit T, et al. Effect of Fluid Intake on Acute Changes in Plasma Volume: A Randomized Controlled Crossover Pilot Trial. Metabolites; 2024: 263. |
| [21] | Drevon L, Maslah N, Soret-Dulphy J, Dosquet C, Ravdan O, Vercellino L, et al. Anemia and hemodilution: analysis of a single center cohort based on 2,858 red cell mass measurements. Haematologica. 2021; 106(4): 1167-71. |
| [22] | Kopytina V, Pascual-Antón L, Toggweiler N, Arriero-País EM, Strahl L, Albar-Vizcaíno P, et al. Steviol glycosides as an alternative osmotic agent for peritoneal dialysis fluid. Front Pharmacol. 2022; 13: 868374. |
| [23] | Lorenz S, Grossklaus R. Risk-benefit analyses of new sugar substitutes: 1. Nutritional-physiological investigations on the osmotic effect and release of glucose in juvenile rats. Nutrition Research. 1984; 4(3): 447-58. |
| [24] | Islam MS, Sakaguchi E. Sorbitol-based osmotic diarrhea: possible causes and mechanism of prevention investigated in rats. World journal of gastroenterology: WJG. 2006; 12(47): 7635. |
| [25] | Hartmann A, Dettmers C, Schott H, Beyenburg S. Cerebral blood flow and rheologic alterations by hyperosmolar therapy in patients with brain oedema. Acta Neurochir Suppl (Wien). 1990; 51: 168-9. |
| [26] | Dallago BS, Braz S, Marçola TG, McManus C, Caldeira DF, Campeche A, et al. Blood Parameters and Toxicity of Chromium Picolinate Oral Supplementation in Lambs. Biol Trace Elem Res. 2015; 168(1): 91-102. |
| [27] | Costa M, Murphy A. Overview of chromium (III) toxicology. The nutritional biochemistry of chromium (III): Elsevier; 2019: 341-59. |
| [28] | Ahmad U, Ahmad RS, Shahbaz M, Imran A, Haseeb M, Siddique F, et al. Hematological and toxicological effects of aqueous leaf extract of Stevia rebaudiana Bertoni in normal rat modals. Pak J Pharm Sci. 2020; 33(5(Supplementary)): 2249-55. |
| [29] | Rashid AH, Mohammed MJ, Hussein FF. The Effect of Dried Stevia Leaves on Some Biochemical Characteristics in the Blood of Diabetic Rats. IOP Conference Series: Earth and Environmental Science, 2024. IOP Publishing: 062011. |
| [30] | Shrivastava R, Nagar R, Ravishankar GA, Upreti RK, Chaturvedi UC. Effect of pretreatment with chromium picolinate on haematological parameters during dengue virus infection in mice. Indian J Med Res. 2007; 126(5): 440-6. |
| [31] | Martínez-Carrillo BE, Rosales-Gómez CA, Ramírez-Durán N, Reséndiz-Albor AA, Escoto-Herrera JA, Mondragón-Velásquez T, et al. Effect of Chronic Consumption of Sweeteners on Microbiota and Immunity in the Small Intestine of Young Mice. Int J Food Sci. 2019; 2019: 9619020. |
| [32] | Chinko BC, Pughikumo DT. Haematological and Hepatorenal Alterations Induced by Potash (Akanwu) on Male Wistar Rats. International Blood Research & Reviews. 2023; 14(1): 38-46. |
| [33] | Pullicin AJ, Glendinning JI, Lim J. Cephalic phase insulin release: A review of its mechanistic basis and variability in humans. Physiol Behav. 2021; 239: 113514. |
| [34] | Pullicin AJ, Lim J. Sweet stimuli induce cephalic phase insulin release to varying degrees in humans. Physiology & Behavior. 2026; 303: 115123. |
| [35] | Dalenberg JR, Patel BP, Denis R, Veldhuizen MG, Nakamura Y, Vinke PC, et al. Short-Term Consumption of Sucralose with, but Not without, Carbohydrate Impairs Neural and Metabolic Sensitivity to Sugar in Humans. Cell Metab. 2020; 31(3): 493-502. e7. |
| [36] | Cefalu WT, Wang ZQ, Zhang XH, Baldor LC, Russell JC. Oral chromium picolinate improves carbohydrate and lipid metabolism and enhances skeletal muscle Glut-4 translocation in obese, hyperinsulinemic (JCR-LA corpulent) rats. J Nutr. 2002; 132(6): 1107-14. |
| [37] | Sahin K, Onderci M, Tuzcu M, Ustundag B, Cikim G, Ozercan IH, et al. Effect of chromium on carbohydrate and lipid metabolism in a rat model of type 2 diabetes mellitus: the fat-fed, streptozotocin-treated rat. Metabolism. 2007; 56(9): 1233-40. |
| [38] | Paiva AN, Lima JG, Medeiros AC, Figueiredo HA, Andrade RL, Ururahy MA, et al. Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study. J Trace Elem Med Biol. 2015; 32: 66-72. |
| [39] | Inyang E, Ijeh II, Oyedemi S. Mixed sweeteners supplemented with chromium picolinate (CrPic) improved some diabetes-related markers and complications in a type 2 diabetic rat model. Nutraceuticals. 2024; 4(4): 658-72. |
| [40] | Edgerton DS, Kraft G, Smith M, Farmer B, Williams PE, Coate KC, et al. Insulin's direct hepatic effect explains the inhibition of glucose production caused by insulin secretion. JCI Insight. 2017; 2(6): e91863. |
| [41] | Lewis GF, Carpentier AC, Pereira S, Hahn M, Giacca A. Direct and indirect control of hepatic glucose production by insulin. Cell metabolism. 2021; 33(4): 709-20. |
| [42] | Jiang S, Young JL, Wang K, Qian Y, Cai L. Diabetic-induced alterations in hepatic glucose and lipid metabolism: The role of type 1 and type 2 diabetes mellitus. Molecular medicine reports. 2020; 22(2): 603-11. |
| [43] | Tsai MJ, Li CH, Wu HT, Kuo HY, Wang CT, Pai HL, et al. Long-Term Consumption of Sucralose Induces Hepatic Insulin Resistance through an Extracellular Signal-Regulated Kinase 1/2-Dependent Pathway. Nutrients. 2023; 15(12). |
| [44] | Romo-Romo A, Sánchez-Tapia M, López-Carrasco MG, Guillén-Pineda LE, Brito-Córdova GX, Martagón AJ, et al. Sucralose consumption modifies glucose homeostasis, gut microbiota, Curli protein, and related metabolites in healthy individuals: A randomized placebo-controlled, triple-blind trial. Clin Nutr ESPEN. 2025; 69: 733-44. |
| [45] | Kurek JM, Król E, Krejpcio Z. Steviol Glycosides Supplementation Affects Lipid Metabolism in High-Fat Fed STZ-Induced Diabetic Rats. Nutrients. 2020; 13(1). |
| [46] | 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. Journal of Functional Foods. 2022; 94: 105141. |
APA Style
Chinko, B. C., Okorodudu, J. E., Nath-Abraham, C., Okafor, A. C., Ikete, P. W., et al. (2026). Evaluation of Subchronic Oral Stevia Supplementation on Haematological Parameters and Serum Metabolic Profile in Male Wistar Rats. Journal of Food and Nutrition Sciences, 14(2), 162-169. https://doi.org/10.11648/j.jfns.20261402.17
ACS Style
Chinko, B. C.; Okorodudu, J. E.; Nath-Abraham, C.; Okafor, A. C.; Ikete, P. W., et al. Evaluation of Subchronic Oral Stevia Supplementation on Haematological Parameters and Serum Metabolic Profile in Male Wistar Rats. J. Food Nutr. Sci. 2026, 14(2), 162-169. doi: 10.11648/j.jfns.20261402.17
@article{10.11648/j.jfns.20261402.17,
author = {Bruno Chukwuemeka Chinko and Juliet Elohor Okorodudu and Chimburuoma Nath-Abraham and Anthonia Chigozie Okafor and Precious Whiskey Ikete and Jennifer Chioma Okeke and Dagbota Dan-Jumbo and Edith Reuben and Price Paul Kwaku Joffa},
title = {Evaluation of Subchronic Oral Stevia Supplementation on Haematological Parameters and Serum Metabolic Profile in Male Wistar Rats},
journal = {Journal of Food and Nutrition Sciences},
volume = {14},
number = {2},
pages = {162-169},
doi = {10.11648/j.jfns.20261402.17},
url = {https://doi.org/10.11648/j.jfns.20261402.17},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jfns.20261402.17},
abstract = {The rising global burden of metabolic disorders has driven increased consumption of non-nutritive sweeteners like stevia as sugar substitutes. While purified steviol glycosides are generally recognised as safe, commercially available stevia products often contain multiple additional ingredients whose combined effects remain inadequately characterised. This study evaluated the subchronic effects of a commercial stevia sweetener on haematological and metabolic parameters in healthy male Wistar rats. Fifteen (15) adult male Wistar (180-200 g) rats were randomly assigned to three groups (n=5 per group): control (distilled water), low-dose stevia (200 mg/kg), and high-dose stevia (400 mg/kg). Treatments were administered daily by oral gavage for eight weeks. Haematological parameters were analysed using an automated haematology analyser, while lipid profile, fasting blood glucose, and insulin were measured spectrophotometrically using standard kits. Stevia supplementation significantly reduced packed cell volume at both doses (p<0.05). The 400 mg/kg dose increased total white blood cell count and reduced platelet count (p<0.05). Monocyte and eosinophil percentages increased at 400 mg/kg and 200 mg/kg, respectively (p<0.05). Metabolically, both doses significantly reduced insulin levels and HOMA-IR values while paradoxically elevating fasting blood glucose (p<0.05). The 400 mg/kg dose significantly increased total cholesterol, triglycerides, and low-density lipoproteins (p<0.05). Evidence from the present study has shown that subchronic commercial stevia supplementation improved insulin sensitivity in healthy rats but concurrently induced haematological and metabolic stress, manifesting as reduced packed cell volume, leukocytosis, hyperglycaemia, and dyslipidaemia. These findings underscore the critical influence of dose and duration context and highlight the need for stevia-based products formulated with fewer potentially harmful additives. The dissociation between improved insulin sensitivity and worsened metabolic control suggests that multiple ingredients may exert opposing effects, warranting further investigation into commercial formulations rather than assuming equivalence to purified steviol glycosides.},
year = {2026}
}
TY - JOUR T1 - Evaluation of Subchronic Oral Stevia Supplementation on Haematological Parameters and Serum Metabolic Profile in Male Wistar Rats AU - Bruno Chukwuemeka Chinko AU - Juliet Elohor Okorodudu AU - Chimburuoma Nath-Abraham AU - Anthonia Chigozie Okafor AU - Precious Whiskey Ikete AU - Jennifer Chioma Okeke AU - Dagbota Dan-Jumbo AU - Edith Reuben AU - Price Paul Kwaku Joffa Y1 - 2026/04/13 PY - 2026 N1 - https://doi.org/10.11648/j.jfns.20261402.17 DO - 10.11648/j.jfns.20261402.17 T2 - Journal of Food and Nutrition Sciences JF - Journal of Food and Nutrition Sciences JO - Journal of Food and Nutrition Sciences SP - 162 EP - 169 PB - Science Publishing Group SN - 2330-7293 UR - https://doi.org/10.11648/j.jfns.20261402.17 AB - The rising global burden of metabolic disorders has driven increased consumption of non-nutritive sweeteners like stevia as sugar substitutes. While purified steviol glycosides are generally recognised as safe, commercially available stevia products often contain multiple additional ingredients whose combined effects remain inadequately characterised. This study evaluated the subchronic effects of a commercial stevia sweetener on haematological and metabolic parameters in healthy male Wistar rats. Fifteen (15) adult male Wistar (180-200 g) rats were randomly assigned to three groups (n=5 per group): control (distilled water), low-dose stevia (200 mg/kg), and high-dose stevia (400 mg/kg). Treatments were administered daily by oral gavage for eight weeks. Haematological parameters were analysed using an automated haematology analyser, while lipid profile, fasting blood glucose, and insulin were measured spectrophotometrically using standard kits. Stevia supplementation significantly reduced packed cell volume at both doses (p<0.05). The 400 mg/kg dose increased total white blood cell count and reduced platelet count (p<0.05). Monocyte and eosinophil percentages increased at 400 mg/kg and 200 mg/kg, respectively (p<0.05). Metabolically, both doses significantly reduced insulin levels and HOMA-IR values while paradoxically elevating fasting blood glucose (p<0.05). The 400 mg/kg dose significantly increased total cholesterol, triglycerides, and low-density lipoproteins (p<0.05). Evidence from the present study has shown that subchronic commercial stevia supplementation improved insulin sensitivity in healthy rats but concurrently induced haematological and metabolic stress, manifesting as reduced packed cell volume, leukocytosis, hyperglycaemia, and dyslipidaemia. These findings underscore the critical influence of dose and duration context and highlight the need for stevia-based products formulated with fewer potentially harmful additives. The dissociation between improved insulin sensitivity and worsened metabolic control suggests that multiple ingredients may exert opposing effects, warranting further investigation into commercial formulations rather than assuming equivalence to purified steviol glycosides. VL - 14 IS - 2 ER -