Non-caloric artificial sweeteners: A mini-review of current perspectives on health benefits and potential risks

Shahin Khalilipanah; Khosrow  Zamani

doi:10.61882/jcbior.5.3.307

Authors

Shahin Khalilipanah Student Research Committee, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
Khosrow Zamani Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

DOI:

https://doi.org/10.61882/jcbior.5.3.307

Keywords:

Artificial sweeteners, Aspartame, Sucralose, Health, Microbiota

Abstract

Non-caloric artificial sweeteners (NAS) have gained widespread use in food, beverages, and pharmaceuticals due to their intense sweetness and minimal caloric contribution. Initially introduced as sugar substitutes for weight management and glycemic control, their safety profiles have come under renewed scrutiny. This mini-review summarizes current evidence on the health benefits and potential risks associated with NAS. Clinical trials support their short-term benefits, including modest reductions in body weight, improved glycemic indices, and dental health advantages due to their non-cariogenic properties. Additionally, certain NAS exhibit antimicrobial and antioxidant activities, although these may also disrupt beneficial gut microbiota. Notably, some epidemiological studies have paradoxically linked NAS consumption with weight gain, metabolic disturbances, and cardiovascular risk. Alterations in gut microbiota, neuroendocrine signaling, and taste perception are proposed mechanisms for these effects. Emerging data also raise concerns about carcinogenic and genotoxic potential, particularly for aspartame and acesulfame-K, although findings remain inconsistent across studies. Regulatory agencies maintain acceptable daily intake limits based on toxicological assessments; however, individual susceptibility, cumulative exposure, and long-term outcomes warrant further investigation. Overall, NAS offer useful alternatives to sugar but should be consumed with awareness of potential systemic and microbiome-mediated risks. Ongoing research, particularly well-designed longitudinal human studies, is essential to inform future dietary recommendations and regulatory policies.

References

1. Basson AR, Rodriguez-Palacios A, Cominelli F. Artificial Sweeteners: History and New Concepts on Inflammation. Front Nutr. 2021;8:746247. DOI: 10.3389/fnut.2021.746247

PMID: 34631773

2. Shum B, Georgia S. The Effects of Non-Nutritive Sweetener Consumption in the Pediatric Populations: What We Know, What We Don't, and What We Need to Learn. Front Endocrinol (Lausanne). 2021;12:625415. DOI: 10.3389/fendo.2021.625415 PMID: 33868167

3. Liauchonak I, Qorri B, Dawoud F, Riat Y, Szewczuk MR. Non-Nutritive Sweeteners and Their Implications on the Development of Metabolic Syndrome. Nutrients. 2019;11(3):644.

DOI: 10.3390/nu11030644 PMID: 30884834

4. Angelin M, Kumar J, Vajravelu LK, Satheesan A, Chaithanya V, Murugesan R. Artificial sweeteners and their implications in diabetes: a review. Front Nutr. 2024;11:1411560.

DOI: 10.3389/fnut.2024.1411560 PMID: 38988858

5. Del Pozo S, Gómez-Martínez S, Díaz LE, Nova E, Urrialde R, Marcos A. Potential Effects of Sucralose and Saccharin on Gut Microbiota: A Review. Nutrients. 2022;14(8):1682.

DOI: 10.3390/nu14081682 PMID: 35458244

6. Butchko HH, Stargel WW, Comer CP, Mayhew DA, Benninger C, Blackburn GL, et al. Aspartame: review of safety. Regul Toxicol Pharmacol. 2002;35(2 Pt 2):S1-93.

DOI: 10.1006/rtph.2002.1542 PMID: 12180494

7. Roberts A, Renwick AG, Sims J, Snodin DJ. Sucralose metabolism and pharmacokinetics in man. Food Chem Toxicol. 2000;38(Suppl 2):S31-41. DOI: 10.1016/s0278-6915(00)00026-0 PMID: 10882816

8. Magnuson BA, Carakostas MC, Moore NH, Poulos SP, Renwick AG. Biological fate of low-calorie sweeteners. Nutr Rev. 2016;74(11):670-689. DOI: 10.1093/nutrit/nuw032

PMID: 27753624

9. Pang MD, Goossens GH, Blaak EE. The Impact of Artificial Sweeteners on Body Weight Control and Glucose Homeostasis. Front Nutr. 2021;7:598340. DOI: 10.3389/fnut.2020.598340 PMID: 33490098

10. Posta E, Fekete I, Gyarmati E, Stündl L, Zold E, Barta Z. The Effects of Artificial Sweeteners on Intestinal Nutrient-Sensing Receptors: Dr. Jekyll or Mr. Hyde? Life (Basel). 2023;14(1):10. DOI: 10.3390/life14010010 PMID: 38276259

11. de Dios R, Proctor CR, Maslova E, Dzalbe S, Rudolph CJ, McCarthy RR. Artificial sweeteners inhibit multidrug-resistant pathogen growth and potentiate antibiotic activity. EMBO Mol Med. 2023;15(1):e16397. DOI: 10.15252/emmm.202216397 PMID: 36412260

12. Prashant GM, Patil RB, Nagaraj T, Patel VB. The antimicrobial activity of the three commercially available intense sweeteners against common periodontal pathogens: an in vitro study. J Contemp Dent Pract. 2012;13(6):749-52. DOI: 10.5005/jp-journals-10024-1222 PMID: 23403996

13. Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514(7521):181-6.

DOI: 10.1038/nature13793 PMID: 25231862

14. Rogers PJ, Hogenkamp PS, de Graaf C, Higgs S, Lluch A, Ness AR, et al. Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies. Int J Obes (Lond). 2016;40(3):381-94. DOI: 10.1038/ijo.2015.177 PMID: 26365102

15. Toews I, Lohner S, Küllenberg de Gaudry D, Sommer H, Meerpohl JJ. Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies. BMJ. 2019;364:k4718.

DOI: 10.1136/bmj.k4718 PMID: 30602577

16. Anton SD, Martin CK, Han H, Coulon S, Cefalu WT, Geiselman P, et al. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite. 2010;55(1):37-43. DOI: 10.1016/j.appet.2010.03.009

PMID: 20303371

17. Grotz VL, Munro IC. An overview of the safety of sucralose. Regul Toxicol Pharmacol. 2009;55(1):1-5.

DOI: 10.1016/j.yrtph.2009.05.011 PMID: 19464334

18. Pepino MY. Metabolic effects of non-nutritive sweeteners. Physiol Behav. 2015;152(Pt B):450-5.

DOI: 10.1016/j.physbeh.2015.06.024 PMID: 26095119

19. Mäkinen KK. Sugar alcohols, caries incidence, and remineralization of caries lesions: a literature review. Int J Dent. 2010;2010:981072. DOI: 10.1155/2010/981072

PMID: 20339492

20. Janakiram C, Deepan Kumar CV, Joseph J. Xylitol in preventing dental caries: A systematic review and meta-analyses. J Nat Sci Biol Med. 2017;8(1):16-21. DOI: 10.4103/0976-9668.198344 PMID: 28250669

21. Edgar WM. Sugar substitutes, chewing gum and dental caries--a review. Br Dent J. 1998;184(1):29-32.

DOI: 10.1038/sj.bdj.4809535 PMID: 9479811

22. Mickenautsch S, Leal SC, Yengopal V, Bezerra AC, Cruvinel V. Sugar-free chewing gum and dental caries: a systematic review. J Appl Oral Sci. 2007;15(2):83-8. DOI: 10.1590/s1678-77572007000200002 PMID: 19089107

23. Schiffman SS, Rother KI. Sucralose, a synthetic organochlorine sweetener: overview of biological issues. J Toxicol Environ Health B Crit Rev. 2013;16(7):399-451.

DOI: 10.1080/10937404.2013.842523 PMID: 24219506

24. Ruiz-Ojeda FJ, Plaza-Díaz J, Sáez-Lara MJ, Gil A. Effects of Sweeteners on the Gut Microbiota: A Review of Experimental Studies and Clinical Trials. Adv Nutr. 2019;10(suppl_1):S31-S48. DOI: 10.1093/advances/nmy037 PMID: 30721958

25. Yu Z, Guo J. Non-caloric artificial sweeteners exhibit antimicrobial activity against bacteria and promote bacterial evolution of antibiotic tolerance. J Hazard Mater. 2022;433:128840. DOI: 10.1016/j.jhazmat.2022.128840

PMID: 35398799

26. Griebsch LV, Theiss EL, Janitschke D, Erhardt VKJ, Erhardt T, Haas EC, et al. Aspartame and Its Metabolites Cause Oxidative Stress and Mitochondrial and Lipid Alterations in SH-SY5Y Cells. Nutrients. 2023;15(6):1467. DOI: 10.3390/nu15061467 PMID: 36986196

27. Fowler SP, Williams K, Resendez RG, Hunt KJ, Hazuda HP, Stern MP. Fueling the obesity epidemic? Artificially sweetened beverage use and long-term weight gain. Obesity (Silver Spring). 2008;16(8):1894-900. DOI: 10.1038/oby.2008.284

PMID: 18535548

28. Nettleton JA, Lutsey PL, Wang Y, Lima JA, Michos ED, Jacobs DR Jr. Diet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care. 2009;32(4):688-94. DOI: 10.2337/dc08-1799 PMID: 19151203

29. Bian X, Chi L, Gao B, Tu P, Ru H, Lu K. The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice. PLoS One. 2017;12(6):e0178426. DOI: 10.1371/journal.pone.0178426 PMID: 28594855

30. Frankenfeld CL, Sikaroodi M, Lamb E, Shoemaker S, Gillevet PM. High-intensity sweetener consumption and gut microbiome content and predicted gene function in a cross-sectional study of adults in the United States. Ann Epidemiol. 2015;25(10):736-42.e4. DOI: 10.1016/j.annepidem.2015.06.083 PMID: 26272781

31. Mossavar-Rahmani Y, Kamensky V, Manson JE, Silver B, Rapp SR, Haring B, et al. Artificially Sweetened Beverages and Stroke, Coronary Heart Disease, and All-Cause Mortality in the Women's Health Initiative. Stroke. 2019;50(3):555-562.

DOI: 10.1161/STROKEAHA.118.023100 PMID: 30802187

32. Abou-Donia MB, El-Masry EM, Abdel-Rahman AA, McLendon RE, Schiffman SS. Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J Toxicol Environ Health A. 2008;71(21):1415-29.

DOI: 10.1080/15287390802328630 PMID: 18800291

33. Balint IB, Erdodi BT. Is there a promoting role for artificial sweeteners in the evolution of bladder cancer? A meta-analysis of current literature. Minerva Surg. 2024;79(1):92-99.

DOI: 10.23736/S2724-5691.23.10000-1 PMID: 37987752

34. Debras C, Chazelas E, Srour B, Druesne-Pecollo N, Esseddik Y, Szabo de Edelenyi F, et al. Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study. PLoS Med. 2022;19(3):e1003950.

DOI: 10.1371/journal.pmed.1003950 PMID: 35324894

35. Martyn D, Darch M, Roberts A, Lee HY, Yaqiong Tian T, Kaburagi N, et al. Low-/No-Calorie Sweeteners: A Review of Global Intakes. Nutrients. 2018;10(3):357.

DOI: 10.3390/nu10030357 PMID: 29543782