Artificial Sweeteners on Brain Health: Neurovascular Changes and Cognitive Decline in Indian Population
Main Article Content
Abstract
In recent years, artificial sweeteners have gained popularity in India's food and beverage sector, largely due to rising concerns about obesity and diabetes. These sweeteners offer benefits such as reduced calorie intake and better blood sugar management. However, emerging research raises concerns about their long-term effects on brain health. This review explores the neurovascular implications of artificial sweeteners and their impact on cognitive decline, particularly among the Indian population. Given the high rates of diabetes and obesity in India, understanding how these sweeteners affect brain function is crucial. Research indicates that artificial sweeteners like aspartame, sucralose, and saccharin are linked to oxidative stress and neuroinflammation, disruptions to the blood-brain barrier, and changes in cerebral blood flow, which could accelerate cognitive decline. Additionally, they may disrupt the gut microbiome and impair the gut-brain axis, worsening neurocognitive issues. For individuals with conditions like type 2 diabetes and obesity, the effects of artificial sweeteners may be particularly severe, increasing the risk of cognitive impairment and neurodegenerative diseases. In conclusion, while artificial sweeteners may offer immediate metabolic benefits, their potential long-term effects on brain health warrant further investigation. With their widespread use in India amidst rising rates of metabolic and neurodegenerative conditions, there is an urgent need for targeted research to assess their safety. Public health strategies should be developed and implemented to educate consumers about the potential cognitive risks associated with artificial sweeteners and to encourage a balanced approach to their consumption.
Keywords:
Artificial Sweeteners, Cognitive Decline, Neurovascular Health, Blood-Brain Barrier, Neuroinflammation, Metabolic Disorders
Article Details
How to Cite
CHOUDHARY, Arbind Kumar.
Artificial Sweeteners on Brain Health: Neurovascular Changes and Cognitive Decline in Indian Population.
Medical Research Archives, [S.l.], v. 13, n. 4, apr. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6388>. Date accessed: 15 may 2025.
doi: https://doi.org/10.18103/mra.v13i4.6388.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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31. Ali A, More TA, Shaikh Z. Artificial sweeteners and their health implications: a review. Biosciences Biotechnology Research Asia. 2021;18(2):227-237.
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36. Schwarz A, Hernandez L, Arefin S, et al. Sweet, bloody consumption–what we eat and how it affects vascular ageing, the BBB and kidney health in CKD. Gut Microbes. 2024;16(1):2341449.
37. Mrad Y. The role of tryptophan dysregulation in a mouse model of migraine. Université Clermont Auvergne; 2023.
38. Kaur R, Das R, Tanwar S, Sajja J. Aspartame and the brain: a systematic review of neurological effects. International Journal of Research in Medical Sciences. 2024;12(8):2977.
39. Jang JH, Kim HK, Seo DW, et al. Whole-brain mapping of the expression pattern of T1R2, a subunit specific to the sweet taste receptor. Frontiers in Neuroanatomy. 2021;15:751839.
40. Mehat K, Chen Y, Corpe CP. The combined effects of aspartame and acesulfame-K blends on appetite: a systematic review and meta-analysis of randomized clinical trials. Advances in Nutrition. 2022;13(6):2329-2340.
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42. Wilk K, Korytek W, Pelczyńska M, Moszak M, Bogdański P. The effect of artificial sweeteners use on sweet taste perception and weight loss efficacy: a review. Nutrients. 2022;14(6):1261.
43. Martinez-Vega MV, Galván-Menéndez-Conde S, Freyre-Fonseca V. Possible Signaling Pathways in the Gut Microbiota–Brain Axis for the Development of Parkinson’s Disease Caused by Chronic Consumption of Food Additives. ACS Chemical Neuroscience. 2023;14(11):1950-1962.
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45. López-Meza MS, Otero-Ojeda G, Estrada JA, Esquivel-Hernández FJ, Contreras I. The impact of nutritive and non-nutritive sweeteners on the central nervous system: preliminary study. Nutritional neuroscience. 2022;25(8):1623-1632.
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47. Morales-Ríos EI, García-Machorro J, Briones-Aranda A, Gómez-Pliego R, Espinosa-Raya J. Effect of long-term intake of nutritive and non-nutritive sweeteners on metabolic health and cognition in adult male rats. Journal of Medicinal Food. 2022;25(11):1059-1065.
48. Song Z, Song R, Liu Y, Wu Z, Zhang X. Effects of ultra-processed foods on the microbiota-gut-brain axis: The bread-and-butter issue. Food Research International. 2023;167:112730.
49. Babatunde OO, Christiana AB, Sunday OI, et al. Comparative effect of selected caloric and non-caloric sweeteners on some neuroinflammatory indices in brain cortex and hippocampus of scopolamine-induced rat. Nutrire. 2024;49(1):13.
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53. Iizuka K. Is the use of artificial sweeteners beneficial for patients with diabetes mellitus? The advantages and disadvantages of artificial sweeteners. Nutrients. 2022;14(21):4446.
54. Savin M, Vrkatić A, Dedić D, et al. Additives in children’s nutrition—A review of current events. International Journal of Environmental Research and Public Health. 2022;19(20):13452.
55. Sebastian MJ, Khan SK, Pappachan JM, Jeeyavudeen MS. Diabetes and cognitive function: An evidence-based current perspective. World journal of diabetes. 2023;14(2):92.
56. Li H, Ren J, Li Y, Wu Q, Wei J. Oxidative stress: The nexus of obesity and cognitive dysfunction in diabetes. Frontiers in endocrinology. 2023;14:1134025.
57. Jones SK, McCarthy DM, Stanwood GD, Schatschneider C, Bhide PG. Learning and memory deficits produced by aspartame are heritable via the paternal lineage. Scientific Reports. 2023;13(1):14326.
58. Chen C, Lu Z, Wang X, Zhang J, Zhang D, Li S. Sugar-sweetened beverages consumption is associated with worse cognitive functions in older adults: from the national health and nutrition examination survey and food patterns equivalents database. Nutritional Neuroscience. 2023;26(10):1011-1018.
59. Zhang Y, Tang Z, Shi Y, Li L. Associations between artificial sweetener intake from cereals, coffee, and tea and the risk of type 2 diabetes mellitus: A genetic correlation, mediation, and mendelian randomization analysis. PloS one. 2024;19(2):e0287496.
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63. Mohan V, Manasa VS, Abirami K, et al. Effect of replacing sucrose in beverages with nonnutritive sweetener sucralose on Cardiometabolic risk factors among Asian Indian adults with type 2 diabetes: a 12-week randomized controlled trial. Diabetes Therapy. 2024;15(9):2061-2077.
64. Mathur K, Agrawal RK, Nagpure S, Deshpande D. Effect of artificial sweeteners on insulin resistance among type-2 diabetes mellitus patients. Journal of family medicine and primary care. 2020;9(1):69-71.
65. Jan S, Ali S. Awareness and Knowledge of Artificial Sweeteners Among Diabetic Patients in Kashmir. International Journal of Health & Medical Sciences. 2024;10
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2. Pillon NJ, Loos RJ, Marshall SM, Zierath JR. Metabolic consequences of obesity and type 2 diabetes: Balancing genes and environment for personalized care. Cell. 2021;184(6):1530-1544.
3. Gupta P, Pushkala K. Two white enemies: salt and sugar. Journal of Cell and Tissue Research. 2022;22(2):7203-7223.
4. Tang CS, Mars M, James J, De Graaf K, Appleton KM. Sweet talk: a qualitative study exploring attitudes towards sugar, sweeteners and sweet-tasting foods in the United Kingdom. Foods. 2021;10(6):1172.
5. Kumar GS, Kulkarni M, Rathi N. Evolving food choices among the urban Indian middle-class: a qualitative study. Frontiers in nutrition. 2022;9:844413.
6. Wierzbicka E. Sweeteners as sugar substitutes in food industry–conditions of use and consumer safety®. Postępy Techniki Przetwórstwa Spożywczego. 2021;(1):186-196.
7. Brewer-Smyth K. Brain Food: The Impact of Diet, Nutrition, and Nutraceuticals on the Brain and the Microbiota-Gut-Brain Axis. Adverse Childhood Experiences: The Neuroscience of Trauma, Resilience and Healing throughout the Life Course. Springer; 2022:303-357.
8. Feng J, Peng J, Hsiao Y-C, et al. Non/Low-Caloric Artificial Sweeteners and Gut Microbiome: From Perturbed Species to Mechanisms. Metabolites. 2024;14(10):544.
9. Fadaei M, Lahijan ASN, Jahanmehr D, Ahmadi A, Asadi-Golshan R. Food additives for the central nervous system, useful or harmful? An evidence-based review. Nutritional Neuroscience. 2025:1-18.
10. Sanjana F. The Effect of Dietary Added Sugar Intake on Cerebrovascular Function and Brain Health. University of Delaware; 2023.
11. Prabhakaran Sobhana P, Nagaraju R, Naik R, Roy V, Shakappa D. Assessment of knowledge and intake of artificial sweeteners among type II diabetic individuals and perspectives of registered dieticians in India. International Journal of Health and Allied Sciences. 2023;12(4):5.
12. Samreen H, Dhaneshwar S. Artificial sweeteners: perceptions and realities. Current Diabetes Reviews. 2023;19(7):131-144.
13. Lam J, Elmore R, Howard B, Shah RR. Low-calorie sweeteners and health outcomes: an evaluation of rapid versus traditional evidence mapping. BMC Research Notes. 2022;15(1):65.
14. Gallagher AM, Ashwell M, Halford JC, Hardman CA, Maloney NG, Raben A. Low-calorie sweeteners in the human diet: scientific evidence, recommendations, challenges and future needs. A symposium report from the FENS 2019 conference. Journal of nutritional science. 2021;10:e7.
15. Erukulapati RS, Ganguri M, Menon AS, et al. Approach to a Newly Diagnosed Adult with Type 2 Diabetes in the Indian Context: Recommendations by Association of Clinical Endocrinologists Consensus Group. Clinical Diabetology. 2023;12(1):6-37.
16. Fuentes JB, Amidžić M, Banović J, Torović L. Internet marketing of dietary supplements for improving memory and cognitive abilities. PharmaNutrition. 2024;27:100379.
17. Sievenpiper JL, Purkayastha S, Grotz VL, et al. Dietary Guidance, Sensory, Health and Safety Considerations When Choosing Low and No-Calorie Sweeteners. Nutrients. 2025;17(5):793.
18. Gillespie KM, White MJ, Kemps E, Moore H, Dymond A, Bartlett SE. The impact of free and added sugars on cognitive function: a systematic review and meta-analysis. Nutrients. 2023;16(1):75.
19. Rao K, Pagote C. Use of Artificial Sweeteners in Indian Traditional Dairy ProductsṪ. Food Nutr J: FDNJ-177 DOI. 2018;10:2575-7091.
20. Newbould E, Pinto A, Evans S, et al. Accidental consumption of aspartame in phenylketonuria: patient experiences. Nutrients. 2021;13(2):707.
21. Dwivedi RS. Search of Sweeteners, Their General Classification, Synthesis, and Saccharide Sweeteners Plant–Animal Interphases. Alternative Sweet and Supersweet Principles: Natural Sweeteners and Plants. Springer; 2022:29-74.
22. Uçar A, Yilmaz S. Saccharin genotoxicity and carcinogenicity: A review. Adv Food Sci. 2015;37(3):138-142.
23. Cros J, Bidlingmeyer L, Rosset R, et al. Effect of nutritive and non-nutritive sweeteners on hemodynamic responses to acute stress: a randomized crossover trial in healthy women. Nutrition & diabetes. 2020;10(1):1.
24. Azeez OH, Alkass SY, Persike DS. Long-term saccharin consumption and increased risk of obesity, diabetes, hepatic dysfunction, and renal impairment in rats. Medicina. 2019;55(10):681.
25. 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.
26. Thomson P, Santibanez R, Aguirre C, Galgani JE, Garrido D. Short-term impact of sucralose consumption on the metabolic response and gut microbiome of healthy adults. British Journal of Nutrition. 2019;122(8):856-862.
27. Ibi D, Suzuki F, Hiramatsu M. Effect of AceK (acesulfame potassium) on brain function under dietary restriction in mice. Physiology & behavior. 2018;188:291-297.
28. Arumugam B, Subramaniam A, Alagaraj P. Stevia as a natural sweetener: a review. Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Cardiovascular & Hematological Agents). 2020;18(2):94-103.
29. Sukhmani G, Yogesh G, Shalini A, Vikas K, Anil P, Ashwani K. Natural sweeteners: health benefits of stevia. Foods and raw materials. 2018;6(2):392-402.
30. Singh AK. Politics of knowledge in development: The case of sugar as an artificial sweetener. Studies in Indian Politics. 2022;10(1):107-117.
31. Ali A, More TA, Shaikh Z. Artificial sweeteners and their health implications: a review. Biosciences Biotechnology Research Asia. 2021;18(2):227-237.
32. Masoodi L, Nissar J, Ahad T, Gull A. Bakery, Confectionery and Beverages as Functional Foods. Functional Foods and Nutraceuticals: Chemistry, Health Benefits and the Way Forward. Springer; 2024:249-275.
33. Sayas-Barberá E, Paredes C, Salgado-Ramos M, et al. Approaches to enhance sugar content in foods: is the date palm fruit a natural alternative to sweeteners? Foods. 2023;13(1):129.
34. Chattopadhyay S, Raychaudhuri U, Chakraborty R. Artificial sweeteners–a review. Journal of food science and technology. 2014;51:611-621.
35. Fadaei M LA, Jahanmehr D, Ahmadi A, Asadi-Golshan R. An evidence-based review. . Food additives for the central nervous system, useful or harmful? . Nutritional Neuroscience. 2025;7:1-8.
36. Schwarz A, Hernandez L, Arefin S, et al. Sweet, bloody consumption–what we eat and how it affects vascular ageing, the BBB and kidney health in CKD. Gut Microbes. 2024;16(1):2341449.
37. Mrad Y. The role of tryptophan dysregulation in a mouse model of migraine. Université Clermont Auvergne; 2023.
38. Kaur R, Das R, Tanwar S, Sajja J. Aspartame and the brain: a systematic review of neurological effects. International Journal of Research in Medical Sciences. 2024;12(8):2977.
39. Jang JH, Kim HK, Seo DW, et al. Whole-brain mapping of the expression pattern of T1R2, a subunit specific to the sweet taste receptor. Frontiers in Neuroanatomy. 2021;15:751839.
40. Mehat K, Chen Y, Corpe CP. The combined effects of aspartame and acesulfame-K blends on appetite: a systematic review and meta-analysis of randomized clinical trials. Advances in Nutrition. 2022;13(6):2329-2340.
41. Tomczyk M, Locatelli M, Granica S. Food/Diet Supplements From Natural Sources: Current Status and Future Challenges From a Pharmacological Perspective. Frontiers Media SA; 2022.
42. Wilk K, Korytek W, Pelczyńska M, Moszak M, Bogdański P. The effect of artificial sweeteners use on sweet taste perception and weight loss efficacy: a review. Nutrients. 2022;14(6):1261.
43. Martinez-Vega MV, Galván-Menéndez-Conde S, Freyre-Fonseca V. Possible Signaling Pathways in the Gut Microbiota–Brain Axis for the Development of Parkinson’s Disease Caused by Chronic Consumption of Food Additives. ACS Chemical Neuroscience. 2023;14(11):1950-1962.
44. Dar W. Aspartame-induced cognitive dysfunction: Unveiling role of microglia-mediated neuroinflammation and molecular remediation. International Immunopharmacology. 2024;135:112295.
45. López-Meza MS, Otero-Ojeda G, Estrada JA, Esquivel-Hernández FJ, Contreras I. The impact of nutritive and non-nutritive sweeteners on the central nervous system: preliminary study. Nutritional neuroscience. 2022;25(8):1623-1632.
46. Gopalakrishnan NK, Balasubramanian B, Kundapur R, Chaudhary A, Meyyazhagnan A, Pappuswamy M. Unraveling connections with artificial sweeteners and their impact on human health: A comprehensive review. eFood. 2024;5(5):e184.
47. Morales-Ríos EI, García-Machorro J, Briones-Aranda A, Gómez-Pliego R, Espinosa-Raya J. Effect of long-term intake of nutritive and non-nutritive sweeteners on metabolic health and cognition in adult male rats. Journal of Medicinal Food. 2022;25(11):1059-1065.
48. Song Z, Song R, Liu Y, Wu Z, Zhang X. Effects of ultra-processed foods on the microbiota-gut-brain axis: The bread-and-butter issue. Food Research International. 2023;167:112730.
49. Babatunde OO, Christiana AB, Sunday OI, et al. Comparative effect of selected caloric and non-caloric sweeteners on some neuroinflammatory indices in brain cortex and hippocampus of scopolamine-induced rat. Nutrire. 2024;49(1):13.
50. Rekha K, Venkidasamy B, Samynathan R, et al. Short-chain fatty acid: An updated review on signaling, metabolism, and therapeutic effects. Critical Reviews in Food Science and Nutrition. 2024;64(9):2461-2489.
51. Naveh-Benjamin M, Cowan N. The roles of attention, executive function and knowledge in cognitive ageing of working memory. Nature Reviews Psychology. 2023;2(3):151-165.
52. Angelin M, Kumar J, Vajravelu LK, Satheesan A, Chaithanya V, Murugesan R. Artificial sweeteners and their implications in diabetes: a review. Frontiers in Nutrition. 2024;11:1411560.
53. Iizuka K. Is the use of artificial sweeteners beneficial for patients with diabetes mellitus? The advantages and disadvantages of artificial sweeteners. Nutrients. 2022;14(21):4446.
54. Savin M, Vrkatić A, Dedić D, et al. Additives in children’s nutrition—A review of current events. International Journal of Environmental Research and Public Health. 2022;19(20):13452.
55. Sebastian MJ, Khan SK, Pappachan JM, Jeeyavudeen MS. Diabetes and cognitive function: An evidence-based current perspective. World journal of diabetes. 2023;14(2):92.
56. Li H, Ren J, Li Y, Wu Q, Wei J. Oxidative stress: The nexus of obesity and cognitive dysfunction in diabetes. Frontiers in endocrinology. 2023;14:1134025.
57. Jones SK, McCarthy DM, Stanwood GD, Schatschneider C, Bhide PG. Learning and memory deficits produced by aspartame are heritable via the paternal lineage. Scientific Reports. 2023;13(1):14326.
58. Chen C, Lu Z, Wang X, Zhang J, Zhang D, Li S. Sugar-sweetened beverages consumption is associated with worse cognitive functions in older adults: from the national health and nutrition examination survey and food patterns equivalents database. Nutritional Neuroscience. 2023;26(10):1011-1018.
59. Zhang Y, Tang Z, Shi Y, Li L. Associations between artificial sweetener intake from cereals, coffee, and tea and the risk of type 2 diabetes mellitus: A genetic correlation, mediation, and mendelian randomization analysis. PloS one. 2024;19(2):e0287496.
60. Clemente-Suárez VJ, Beltrán-Velasco AI, Redondo-Flórez L, Martín-Rodríguez A, Tornero-Aguilera JF. Global impacts of western diet and its effects on metabolism and health: A narrative review. Nutrients. 2023;15(12):2749.
61. Bai B, Chen H. Metformin: a novel weapon against inflammation. Frontiers in pharmacology. 2021;12:622262.
62. Li N, Zhou T, Fei E. Actions of metformin in the brain: a new perspective of metformin treatments in related neurological disorders. International Journal of Molecular Sciences. 2022;23(15):8281.
63. Mohan V, Manasa VS, Abirami K, et al. Effect of replacing sucrose in beverages with nonnutritive sweetener sucralose on Cardiometabolic risk factors among Asian Indian adults with type 2 diabetes: a 12-week randomized controlled trial. Diabetes Therapy. 2024;15(9):2061-2077.
64. Mathur K, Agrawal RK, Nagpure S, Deshpande D. Effect of artificial sweeteners on insulin resistance among type-2 diabetes mellitus patients. Journal of family medicine and primary care. 2020;9(1):69-71.
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