Natural and Artificial Sweeteners a Blessing or Curse: A Phyto-genotoxic Study in Allium cepa L. Root Tip Cells
DOI:
https://doi.org/10.38211/joarps.2026.07.336Keywords:
Sweeteners, Phytotoxicity, Genotoxicity, Allium cepa L, Oxidative damages, CarcinogenesisAbstract
The study investigated the comparative phyto-genotoxic impacts of natural and artificial sweetener brands using the Allium cepa L. (onion) assay to predict potential phyto-genotoxic associated with long-term intake. Onion bulbs were exposed for 48hours to 1% aaqueous solutions of natural and artificial sweeteners (Honey, Date, Jaggery, Canderel, Sucral, Stiva and Refined sugar) and distilled water was used as the negative control. All the tested sweeteners exhibited significant variations at LSD≤0.05 for all phytotoxicity and genotoxicity parameters. The results phytotoxicity, characterized by a marked failure of root emergence and reduction in root length and Mitotic index (M.I.%). Genotoxic analysis showed that both sweetener categories induced a substantial increase in Abnormality Index (A.I.%), escalating from 14.2% at the lowest concentration to 47.2% at the highest. The most prevalent chromosomal aberration was DNA fragmentation in all the tested sweeteners and while occurrences of sticky metaphase and micronuclei were also recorded in low number. Stiva induced nuclear lesions, and impaired chromosome condensation. These two are checkpoints of carcinogenesis in addition to chromosomal aberrations. The high frequency of nuclear damage and cellular membrane irregularities suggests that exposure to 1% solutions of both natural and artificial sweeteners can induce measurable genetic instability. Overall results suggest that Stiva followed by Canderel, Sucral and refined sugar were severely phyto-genotoxic, while honey was moderately phyto-genotoxic and Dates followed by jaggery were the mild phyto-genotoxic. It is concluded that sweetener intake must be minimized to avoid possible cellular and DNA damages. A dose dependent animal-based study must be conducted to estimate cancer risk to humans. Reactive oxygen species generation, lipid peroxidation profiling is also recommended.
Downloads
References
Abdelbaky, A.S., Tammam, M.A., Ali, M.Y., Sharaky, M., Selim, K., Semida, W.M., Abd El-Mageed, T.A., Ramadan, M.F., Oraby, H.F., Diab, Y.M. (2023). Antioxidant and Anticancer Assessment and Phytochemical Investigation of Three Varieties of Date Fruits. Metabolites, 13 (7), 816. DOI: 10.3390/metabo13070816. DOI: https://doi.org/10.3390/metabo13070816
Arshad, S., Rehman, T, Sail, S., Rajoka, M.S.R., Ranjha, M.M.A.N., Hassoun, A., Cropotova, J., Trif, M., Younas, A. and Aadil, R.N. (2022). Replacement of refined sugar by natural sweeteners: focus on potential health benefits. Heliyon, 8(9), e10711. DOI: org/10.1016/j.heliyon.2022.e10711. DOI: https://doi.org/10.1016/j.heliyon.2022.e10711
Atalay, E.C., Celep, A.G.S., Catanzaro, R. and Marotta F. (2025). Aspartame, saccharin, sucralose, and stevia: Oxidative stress pathways and functional food perspectives. Bioactive Compounds in Health and Disease, 8(11), 474-48. DOI: https://doi.org/10.31989/bchd.v8i11.1804
Banerjee, A., Das, D., Maji, B.K., and Mukherjee, S. (2018). An in vitro cytotoxic activity of Bees’ honey in Huh-7 cell line. Biotechnology and Microbiology, 9 (1), 555751. DOI: 10.19080/AIBM.2018.09.555751. DOI: https://doi.org/10.19080/AIBM.2018.09.555751
Berry, A., Ruzzene, S., Izaias, J., Holzer, J., Stone, M., Orozco-Fersiva, N., Greiner, W.V.J., Garcia V.P. and DeSouza, C.(2025) Erythritol Increases Oxidative Stress and Reduces Nitric Oxide Production in Human Cerebral Microvascular Endothelial Cells. Physiology, 40, (1) https://doi.org/10.1152/physiol.2025.40.S1.1054 DOI: https://doi.org/10.1152/physiol.2025.40.S1.1054
Bezerra, M.D.S., Malaquias, G.D.S., Castro e sousa, J.M.D. and Peron, A.P. (2016). Cytotoxic and genotoxic potential of powdered juices. Food Science and Technology, 36(1), 49-55. DOI: 10.1590/1678-457X.0006. DOI: https://doi.org/10.1590/1678-457X.0006
Cavalli, G. and Misteli, T. (2013). Functional implications of genome topology. Nature Structural and Molecular Biology, 20(3), 290-299. DOI: https://doi.org/10.1038/nsmb.2474
Channar, A.P., Sadaf Tabasum Qureshi1, S.T., Soomro, A.N., Saddar A.N., Sadia (2025). DNA damaging effects of lotion vs electric mosquito repellent assessed via chickpea chromosomal aberration assay. Journal of Applied Research in Plant Sciences, 6 (2), 143-154. https://doi.org/10.38211/joarps.2025.06.323. DOI: https://doi.org/10.38211/joarps.2025.06.323
Debras, C., Chazelas, E., Srour, B., Druesne-Pecollo,N., Esseddik, Y., Edelenyi, F.S.D., Agae, C., Sa, A.D., Lutchia, R., Gigandet, S., Huybrechts, I., Julia, C., Kesse-Guyot, E., Alles, B., Andreeva, V.A., Galan, P., Hercberg, S., Deschasaux-Tanguy, M.l., Touvier, M. (2022). Artificial sweeteners and cancer risk: Results from the NutriNet-Sante´ population-based cohort study. PLoS Medicine, 19 (3), e1003950. DOI: 10.1371/journal.pmed.1003950. DOI: https://doi.org/10.1371/journal.pmed.1003950
EFSA FAF Panel (EFSA Panel on Food Additives and Flavourings . (2021). Scientific opinion on the safety evaluation of steviol glycoside preparations, including rebaudioside AM, obtained by enzymatic bioconversion of highly purified stevioside and/or rebaudioside a stevia leaf extracts. EFSA Journal, 19(8), 6691. DOI:10.2903/j.efsa.2021.6691. DOI: https://doi.org/10.2903/j.efsa.2021.6691
Firbas, P., and Amon, T. (2014). Chromosome damage studies in the onion plant Allium cepa L. International Journal of Cytology, Cytosystematics and Cytogenetics, 67 (1), 25-35. DOI: https://doi.org/10.1080/00087114.2014.891696
Helal, E.G.E. , Abdelaziz, M.A. , El-Gamal, M.S. (2019). Effects Of CANDEREL® and the ameliorative role of stem cell eenhancer on some physiological parameters in male albino rats. The Egyptian Journal of Hospital Medicine,76 (3), 3702-3708. DOI: https://doi.org/10.21608/ejhm.2019.39915
Hirpara, P., Thakare, N., Kele, V.D., and Patel, D. (2020). Jaggery: A natural sweetener. Journal of Pharmacognosy and Phytochemistry, 9(5), 3145-3148.
Ibrahim, E.S., Ragheb, E.M., Yousef, F.M., Abdel-Aziz, M.F., and Alghamd, B.A. (2020). Nutritional value, cytotoxic and antimicrobial activities of Stevia rebaudiana leaf extracts. Journal of Biochemical Technology, 11(12), 108-115.
International Diabetic Federation (I.D.F). 2024, https://idf.org/our-network/regions-and-members/middle-east-and-north-africa/members/pakistan/.
Ismail, I., Zakaria, N.F., Yong, J.H. Y., Ismail, N. (2025). Lessons From Practice: Severe Hyperkalemia and life-threatening events after dates consumption during Ramadan in end-stage renal failure patient. Malaysian Journal of Emergency Medicine, 7(1): 41-43. DOI: https://doi.org/10.64392/5bw7mn71
Kulkarni, A.S., Karkhanis, D., Barve, S.S. and Sharma, S. (2021). Antioxidant and cytotoxic study of extract of vegetative and flowering stages leaves Stevia rebaudiana. Journal of Pharmacognosy and Phytochemistry, 10 (4), 303-306.
Lanctôt, C., Cheutin, T., Cremer, M., Cavalli, G. and Cremer, T. (2007). Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions. Nature Reviews Genetics, 8(2), 104-15.DOI: 10.1038/nrg2041. DOI: https://doi.org/10.1038/nrg2041
Magliano, D.J., Boyko, E.J. (2021). IDF Diabetes Atlas 10th edition scientific committee. 10th edition. Brussels: International Diabetes Federation; 2021. Chapter 3, Global picture. Available from: https://www.ncbi.nlm.nih.gov/books/NBK 581940/.
Meenatchi, M., Vellapandian, C. (2024). Exploring the Long-Term Effect of Artificial Sweeteners on Metabolic Health. Cureus, 16(9), e70043. DOI: 10.7759/cureus.70043. DOI: https://doi.org/10.7759/cureus.70043
Mongi, R.J. and Ruhembe, C.C. (2024). Sugar profile and sensory properties of honey from different geographical zones and botanical origins in Tanzania. Heliyon, 10 (18), e38094. doi: 10.1016/j.heliyon.2024.e38094. DOI: https://doi.org/10.1016/j.heliyon.2024.e38094
Nurcayani, N., Barliana, M.I., Dandan, K.L. (2025). Cytotoxic effects of tea (Camellia sinensis), stevia (Stevia rebaudiana), moringa (Moringa oleifera) leaves, and their potential as functional beverages for cancer patients. Bioactive Compounds in Health and Disease, 8 (8), 292 – 307. Doi.org/10.31989/bchd.v8i8.1690. DOI: https://doi.org/10.31989/bchd.v8i8.1690
Nuryandani, E., Kurnianto, D., Jasmadi, J., Sefrienda, A.R., Novitasari, E., Apriyati, E., Wanita, Y.P., Indrasari, S.D., Sunaryanto, R., Tjokrokusumo, D., Yani, A., Suryaningtyas, I.T., and Andriana,Y. (2024). Phytotoxic and Cytotoxic Effects, Antioxidant Potentials, and Phytochemical Constituents of Stevia rebaudiana Leaves. Scientifica, 2024, 2200993. https://doi.org/10.1155/2024/2200993. DOI: https://doi.org/10.1155/2024/2200993
Ogwu, M.C. and Izah, S.C. (2025). Honey as a Natural Antimicrobial. Antibiotics, 14 (255), 1-29. https://doi.org/10.3390/ antibiotics14030255. DOI: https://doi.org/10.3390/antibiotics14030255
Oliveira, V.A.D., Oliveira, V.M.A.D., Oliveira, T.W.N.D., Damasceno, A.N.C., Silva, C.E.D.O, Medeiros, S.R.A., Soares, B.M., Silva, F.C.C.D., Aguiar, R.P.S.D., Islam, M.T., MeloCavalcante, A.A.D.C., Peron, A.P., and Sousa, J.M.D.C.E. (2017). Evaluation of cytotoxic and mutagenic effects of two artificial sweeteners using eukaryotic test system. African Journal of Biotechnology, 6 (11), 547-551. https://doi.org/10.5897/AJB2016.15695. DOI: https://doi.org/10.5897/AJB2016.15695
Orellana-Paucar, A.M. (2023). Steviol Glycosides from Stevia rebaudiana: An Updated Overview of Their Sweetening Activity, Pharmacological Properties, and Safety Aspects. Molecules, 28, 1258. https://doi.org/10.3390/ molecules28031258. DOI: https://doi.org/10.3390/molecules28031258
Perrier, J.D. Mihalov, J.J., Carlson, S.J. (2018). FDA regulatory approach to steviol glycosides. Food and Chemical Toxicology, 122, 132-142. https://doi.org/10.1016/j.fct.2018.09.062. DOI: https://doi.org/10.1016/j.fct.2018.09.062
Prakash, M.D., Stojanovska, L., Feehan, J., Nurgali, K. , Donald, E.L., Plebanski, FlavelI, M., Kitchen, B., Apostolopoulos, V. (2021). Anti-cancer effects of polyphenol-rich sugarcane extract. PloS One, 16 (3), e0247492. Doi.org/10.1371/journal.pone.0247492. DOI: https://doi.org/10.1371/journal.pone.0247492
Qureshi, S. T., Chandio, P., Noman, A., Parveen, A., and Soomro, Y. (2015). Cytotoxic and genotoxic and oxidative effects of aqueous extract of some frequently used medicinalplants in Pakistan. Botany Research International, 8 (1): 29-35.
Racuciu, M. (2009). Effect of radiofrequency radiation on root tip cells of Zea mays. Romanian Biotechnologycal Letters, 14 (3): 4365–4369.
Sachan, M. and Singh P. (2026). Artificial Sweeteners: Chemistry, Health Impacts and Regulatory Perspectives. Asian Journal of Pharmaceutical Research and Development, 13(5), 39-43. DOI: 10.22270/ajprd.v13i5.1624. DOI: https://doi.org/10.22270/ajprd.v13i5.1624
Sadia, Qureshi, S.T., Soomro. A.N., Malik, S. Punar, Z. (2024). Mutational and carcinogenic potential of Amaltas fruit via oxidation. Journal of Applied Research in Plant Sciences, 5(2), 269-280. https://doi.org/10.38211/joarps.2024.05.276. DOI: https://doi.org/10.38211/joarps.2024.05.276
Selvapriya, S., Priyadharshini, R., Kumar, S.R., and Sinduja, P. (2021). Anti-Inflammatory and Cytotoxic Effect of Stevia and Neem Based Herbal Formulation. Journal of Pharmaceutical Research International, 33(59(A)), 150-160. DOI: 10.9734/JPRI/2021/v33i59A34259. DOI: https://doi.org/10.9734/jpri/2021/v33i59A34259
Tkach V.V., Morozova, T.V., Gaivão, I.O., Gomes de Miranda. N., Ivanushko. Y.G., Martins J.I.F., Barros, A.N. (2025). Sucralose: A review of environmental, oxidative and genomic Stress. Nutrients, 17(13), 2199. doi: 10.3390/nu17132199. DOI: https://doi.org/10.3390/nu17132199
Wisal, A., Asad-Ullah, Khan, B., Sıcak,Y., Öztürk, M., Muhammad, A., Anwar, W., Begum, S., Zafar, S., Carvalho, P.V.S.D., Hassan, S.S., Halim, S.A., Khan, A. (2025). The cytotoxic, antioxidant, and anticholinesterase activity of steviol and isosteviol analogues, together with structure-activity relationships and molecular docking studies. Journal of Molecular Structure, 1345, 43049. DOI: https://doi.org/10.1016/j.molstruc.2025.143049
Xu, X., Wand, Q., Li, B., Liu, C., Cu, C., Yi, M., Zhai, L., Wong, R.M.Y., Zhang. N. and Cheung, W.C. (2025). Effect of artificial sweeteners on the Musculoskeletal system: A systematic review of current evidence. Nutrients, 17(21).3489. http://doi.org/.10.3390/nul17213489. DOI: https://doi.org/10.3390/nu17213489
Zahadi, N.A. Berahim, Z. and Zainuddin, S.L. (2026). Evaluating the effect of Tualang honey on the viability and migration of human gingival fibroblasts. Journal of Orofacial and Health , 7(1), 28-39. https://doi.org/10.31436/ijohs.v7i1.425. DOI: https://doi.org/10.31436/ijohs.v7i1.425
Zink, D., Fischer, A.H. and Nickerson, J.A. (2004). Nuclear structure in cancer cells. Nature Reviews Cancer, 4(9), 677-87.DOI: 10.1038/nrc1430. DOI: https://doi.org/10.1038/nrc1430
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Sadaf Tabasum Qureshi, Sindhu Zahid, Muhammad Ramzan Laghari, Shafique Ahmed Rajper, Shamshad Ali Jarwar, Sooraj Kumar Bheel, Kainat Anwar Arian

This work is licensed under a Creative Commons Attribution 4.0 International License.