Short-Term Effects of Sucralose and Saccharin on Blood Sugar and Gut Microbiota in Type 2 Diabetes
- Conditions
- Type 2 Diabetes Mellitus (T2DM)
- Registration Number
- NCT07124585
- Lead Sponsor
- National University of Malaysia
- Brief Summary
This clinical trial investigates the short-term effects of two commonly used non-nutritive sweeteners (NNS), saccharin and sucralose, on blood glucose regulation and the gut microbiota in adults with Type 2 Diabetes Mellitus (T2DM). While NNS are widely promoted as sugar substitutes to aid glycaemic control, emerging evidence suggests that even small doses may influence metabolic health, potentially through interactions with the gut microbial community.
The study is designed as a double-blind, randomized, placebo-controlled, crossover trial involving 33 adults with T2DM. Each participant will receive all three interventions, saccharin, sucralose, and a placebo (calcium carbonate) in random order. Each intervention will be administered once daily in capsule form for 7 consecutive days, with a 4-week washout period between phases to minimize carryover effects.
Throughout the trial, data will be collected on anthropometry, blood-based glycaemic biomarkers, dietary intake, physical activity, and stool samples. Gut microbiota composition will be assessed via 16S rRNA gene sequencing.
The primary aim is to generate evidence on whether short-term exposure to NNS can affect glycaemic outcomes and gut microbial profiles in individuals with T2DM. The findings are expected to support future dietary recommendations on NNS use and improve our understanding of diet-microbiota-host interactions, particularly within Asian populations.
- Detailed Description
Although these sweeteners are generally recognized as safe, emerging studies have raised concerns regarding their potential metabolic effects
\[1\]. In particular, findings on their influence on glycaemic control in humans remain inconsistent \[2\]. One proposed mechanism underlying these effects involves modulation of the gut microbiota, which is increasingly recognised as a critical regulator of host metabolic homeostasis \[3\]. However, current evidence in human studies is limited and inconclusive.
Individuals with T2DM commonly exhibit pre-existing gut dysbiosis \[4\], raising important questions about whether the use of NNS may further impair microbial composition or function. To date, no clinical trial has comprehensively examined the short-term effects of sucralose and saccharin on both glycaemic responses and the gut microbiota in specific T2DM population. Moreover, data from Asian populations whose dietary patterns, gut microbial composition, and metabolic phenotypes differ significantly from Western cohorts are scarce. Given the widespread consumption of NNS in daily diets, especially among individuals seeking glycaemic control, this represents a critical evidence gap with potential implications for dietary recommendations and metabolic health.
This study aims to address these gaps through a clinical trial in adults with T2DM. The crossover design enables within-subject comparisons, thereby reducing inter-individual variability and enhancing statistical power to detect subtle biological effects. Reference to previous studies has shown inconsistencies arising from factors such as inconsistent dosing, varying administration routes (e.g., sachet vs. capsule; pure compound vs. commercial product), differences in intervention duration, and a lack of control for confounding variables such as habitual diet, medication use, and physical activity \[5-10\]. To address these issues, we have incorporated several methodological improvements. Our study will implement a body weight-based individual dosing protocol, oral administration in a standardised pure compound capsule form, and detailed characterisation of participants' dietary intake and lifestyle behaviours.
Additionally, for our study phenotype, we have strictly controlled for patients' diabetes progression, including diagnosis duration (1-5 years), treatment type (oral antidiabetic medication only, no insulin), age group (30-50 years), demographic (male only), ethnicity (single ethnic group), and BMI range (specified). Through these measures, our study aims to minimise variability, particularly in gut microbiota outcomes and generate more robust results.
References
1. Brown, R. J., de Banate, M. A., \& Rother, K. I. (2010). Artificial sweeteners: a systematic review of metabolic effects in youth. International journal of pediatric obesity : IJPO : an official journal of the International Association for the Study of Obesity, 5(4), 305-312. https://doi.org/10.3109/17477160903497027
2. Toews, I., Lohner, S., Küllenberg de Gaudry, D., Sommer, H., \& Meerpohl, J. J. (2019). 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 (Clinical research ed.)\*, \*364\*, k4718. https://doi.org/10.1136/bmj.k4718
3. Wu, J., Wang, K., Wang, X., Pang, Y., \& Jiang, C. (2021). The role of the gut microbiome and its metabolites in metabolic diseases. Protein \& cell, 12(5), 360-373. https://doi.org/10.1007/s13238-020-00814-7
4. Zhou, Z., Sun, B., Yu, D., \& Zhu, C. (2022). Gut Microbiota: An Important Player in Type 2 Diabetes Mellitus. Frontiers in cellular and infection microbiology, 12, 834485. https://doi.org/10.3389/fcimb.2022.834485
5. Méndez-García, L. A., Bueno-Hernández, N., Cid-Soto, M. A., De León, K. L., Mendoza-Martínez, V. M., Espinosa-Flores, A. J., Carrero-Aguirre, M., Esquivel-Velázquez, M., León-Hernández, M., Viurcos-Sanabria, R., Ruíz-Barranco, A., Cota-Arce, J. M., Álvarez-Lee, A., De León-Nava, M. A., Meléndez, G., \& Escobedo, G. (2022). Ten-Week Sucralose Consumption Induces Gut Dysbiosis and Altered Glucose and Insulin Levels in Healthy Young Adults. Microorganisms, 10(2), 434. https://doi.org/10.3390/microorganisms10020434
6. Thomson, P., Santibañez, R., Aguirre, C., Galgani, J. E., \& Garrido, D. (2019). Short-term impact of sucralose consumption on the metabolic response and gut microbiome of healthy adults. The British journal of nutrition, 122(8), 856-862. https://doi.org/10.1017/S0007114519001570
7. Ahmad, S. Y., Friel, J., \& Mackay, D. (2020). The Effects of Non-Nutritive Artificial Sweeteners, Aspartame and Sucralose, on the Gut Microbiome in Healthy Adults: Secondary Outcomes of a Randomized Double-Blinded Crossover Clinical Trial. Nutrients, 12(11), 3408. https://doi.org/10.3390/nu12113408
8. Suez, J., Cohen, Y., Valdés-Mas, R., Mor, U., Dori-Bachash, M., Federici, S., Zmora, N., Leshem, A., Heinemann, M., Linevsky, R., Zur, M., Ben-Zeev Brik, R., Bukimer, A., Eliyahu-Miller, S., Metz, A., Fischbein, R., Sharov, O., Malitsky, S., Itkin, M., Stettner, N., ... Elinav, E. (2022). Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell, 185(18), 3307-3328.e19. https://doi.org/10.1016/j.cell.2022.07.016
9. Serrano, J., Smith, K. R., Crouch, A. L., Sharma, V., Yi, F., Vargova, V., LaMoia, T. E., Dupont, L. M., Serna, V., Tang, F., Gomes-Dias, L., Blakeslee, J. J., Hatzakis, E., Peterson, S. N., Anderson, M., Pratley, R. E., \& Kyriazis, G. A. (2021). High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice. Microbiome, 9(1), 11. https://doi.org/10.1186/s40168-020-00976-w
10. Suez, J., Korem, T., Zeevi, D., Zilberman-Schapira, G., Thaiss, C. A., Maza, O., Israeli, D., Zmora, N., Gilad, S., Weinberger, A., Kuperman, Y., Harmelin, A., Kolodkin-Gal, I., Shapiro, H., Halpern, Z., Segal, E., \& Elinav, E. (2014). Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature, 514(7521), 181-186. https://doi.org/10.1038/nature13793
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Male
- Target Recruitment
- 33
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Primary Outcome Measures
Name Time Method Glycaemic control 6 months The primary outcome of this study is to assess the change in glycaemic control, measured by insulin sensitivity using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), which will be calculated from fasting glucose and insulin levels following NNS consumption
- Secondary Outcome Measures
Name Time Method Gut microbiota composition and diversity 6 months The secondary outcome is to evaluate changes in gut microbiota composition and diversity following NNS consumption. Microbiota outcomes will be assessed via 16S rRNA gene sequencing. Alpha diversity and beta diversity metrics will be used to evaluate within- and between-group microbiota differences. Differential abundance analysis will be conducted to identify specific taxanomy associated with each intervention.
Trial Locations
- Locations (1)
Klinik Kesihatan Setapak
🇲🇾Kuala Lumpur, Malaysia
Klinik Kesihatan Setapak🇲🇾Kuala Lumpur, MalaysiaMedical DoctorContact603 4142 4052suhailinaim@gmail.com