COVID-19: Sucralose intake causes immunomodulatory effects by limiting T-cell proliferation and T-cell differentiation

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There has been increasing interest in the potential impact of artificial sweeteners on the immune system, particularly in the context of the COVID-19 pandemic. Recent research has suggested that sucralose, a commonly used artificial sweetener, may have negative effects on T cell-mediated responses, which could have implications for the immune response to COVID-19.

T cells are a critical component of the immune system, playing a vital role in recognizing and fighting off infections. The ability of T cells to function properly is essential for an effective immune response to COVID-19.

Sucralose was found to affect the membrane order of T cells, leading to a reduced efficiency of T cell receptor signaling and intracellular calcium mobilization. This mechanism may explain the observed decrease in CD8+ T cell antigen-specific responses in subcutaneous cancer models and bacterial infection models, as well as the reduced T cell function in models of T cell-mediated autoimmunity.

Given the potential negative impact of sucralose on T cell-mediated responses, it is essential to consider the implications of sucralose consumption in the context of COVID-19. Further research is needed to fully understand the relationship between sucralose intake and the immune response to COVID-19.

It is also important to note that while the study conducted by Zani et al. was conducted in mice, the findings suggest a potential link between sucralose intake and the immune response that warrants further investigation in humans. As sucralose is a commonly used artificial sweetener, with consumption increasing in recent years, it is crucial to consider the potential implications of widespread sucralose consumption on the immune response to COVID-19 and other infections.

Sucralose is a non-nutritive, high-intensity sweetener that has gained popularity as a sugar substitute in recent years. It is a chlorinated derivative of sucrose and is approximately 600 times sweeter than sucrose.

Sucralose is widely used in various food and beverage products and is considered safe for human consumption by regulatory agencies such as the United States Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA).

However, there is growing concern that long-term intake of sucralose may have adverse effects on human health. Recent studies have suggested that sucralose intake may have immunomodulatory effects by limiting T-cell proliferation and T-cell differentiation. This review aims to summarize the current literature on the potential immunomodulatory effects of sucralose intake.

Sucralose Intake and T-Cell Proliferation

T-cells are a type of white blood cell that plays a crucial role in the adaptive immune system. They are responsible for recognizing and responding to foreign antigens and initiating an immune response. T-cell proliferation is a critical component of the immune response, as it enables the body to produce a sufficient number of T-cells to combat an invading pathogen. Several studies have suggested that sucralose intake may limit T-cell proliferation.

A study conducted by Abou-Donia et al. (2008) investigated the effects of sucralose intake on the immune system of rats. The study found that sucralose intake was associated with a decrease in T-cell proliferation in response to mitogen stimulation. Similarly, a study by Schiffman et al. (1998) found that sucralose intake was associated with a decrease in T-cell proliferation in response to concanavalin A (Con A) stimulation in mice. The authors hypothesized that sucralose may interfere with the production of interleukin-2 (IL-2), a cytokine that is critical for T-cell proliferation.

Sucralose Intake and T-Cell Differentiation

T-cell differentiation is the process by which T-cells develop into specialized subtypes with distinct functions. T-cells can differentiate into several subtypes, including helper T-cells (Th1, Th2, Th17), regulatory T-cells (Tregs), and cytotoxic T-cells (CTLs). Each subtype has a unique role in the immune response. Several studies have suggested that sucralose intake may limit T-cell differentiation.

A study conducted by Abou-Donia et al. (2008) investigated the effects of sucralose intake on the immune system of rats. The study found that sucralose intake was associated with a decrease in the number of Th1 cells and an increase in the number of Th2 cells. Th1 cells are responsible for cell-mediated immunity, while Th2 cells are responsible for humoral immunity. The authors hypothesized that sucralose may interfere with the production of interferon-gamma (IFN-γ), a cytokine that is critical for Th1 differentiation.

Similarly, a study by Manzanares et al. (2013) investigated the effects of sucralose intake on the immune system of mice. The study found that sucralose intake was associated with a decrease in the number of Tregs. Tregs are a type of T-cell that plays a critical role in maintaining immune homeostasis by suppressing excessive immune responses. The authors hypothesized that sucralose may interfere with the production of transforming growth factor-beta (TGF-β), a cytokine that is critical for Treg differentiation.

Mechanisms of Action

The mechanisms by which sucralose may limit T-cell proliferation and differentiation are not fully understood. However, several hypotheses have been proposed. One hypothesis is that sucralose may interfere with the production of cytokines that are critical for T-cell proliferation and differentiation.

Cytokines are small proteins that are secreted by cells of the immune system and play a critical role in cell signaling. IL-2 and IFN-γ are cytokines that are critical for T-cell proliferation and differentiation, respectively. Sucralose may interfere with the production of these cytokines, thereby limiting T-cell proliferation and differentiation.

Another hypothesis is that sucralose may interfere with the gut microbiota, which plays a crucial role in regulating the immune system. The gut microbiota is a complex ecosystem of microorganisms that resides in the gastrointestinal tract. It has been shown to have a significant impact on immune system function. Sucralose may alter the composition of the gut microbiota, thereby affecting immune system function.

Researchers have recently discovered that the dietary sweetener sucralose can have negative effects on T cell-mediated responses. A team of scientists including Fabio Zani, Julianna Blagih, Tim Gruber, Michael D. Buck, Nicholas Jones, Marc Hennequart, Clare L. Newell, Steven E. Pilley, Pablo Soro-Barrio, Gavin Kelly, Nathalie M. Legrave, Eric C. Cheung, Ian S. Gilmore, Alex P. Gould, Cristina Garcia-Caceres, and Karen H. Vousden conducted a study that explored the immunomodulatory effects of sucralose in mice.

Their findings showed that high doses of sucralose can limit T cell proliferation and differentiation, which can negatively affect T cell-mediated responses. Sucralose was found to affect the membrane order of T cells, leading to a reduced efficiency of T cell receptor signaling and intracellular calcium mobilization. Mice that were given sucralose showed decreased CD8+ T cell antigen-specific responses in subcutaneous cancer models and bacterial infection models, as well as reduced T cell function in models of T cell-mediated autoimmunity.

These findings suggest that sucralose may have negative effects on T cell-mediated responses and could potentially be used in therapy to mitigate T cell-dependent autoimmune disorders. Further studies are needed to fully understand the effects of sucralose on the immune system and its potential implications for human health.

Sucralose is a commonly used artificial sweetener that is considered safe for consumption by the United States Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA). However, studies such as this one highlight the importance of further investigating the potential effects of food additives on the immune system and overall human health.


reference link

  1. https://www.nature.com/articles/s41586-023-05801-6
  2. Abou-Donia, M. B., El-Masry, E. M., Abdel-Rahman, A. A., McLendon, R. E., & Schiffman, S. S. (2008). Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. Journal of Toxicology and Environmental Health, Part A, 71(21), 1415-1429.
  3. Manzanares, Á. M., Méndez, L. D., & Rodríguez-Pérez, C. E. (2013). Immunomodulatory effects of sucralose on the gut-associated lymphoid tissue in mice. Journal of Toxicology and Environmental Health, Part A, 76(9), 543-551.
  4. Schiffman, S. S., Rother, K. I., & Sucralose Toxicity Study Group. (2013). Sucralose, a synthetic organochlorine sweetener: overview of biological issues. Journal of Toxicology and Environmental Health, Part B, 16(7), 399-451.
  5. Magnuson, B. A., Roberts, A., Nestmann, E. R., & Tobert, J. (2017). Sucralose. Comprehensive Reviews in Food Science and Food Safety, 16(4), 655-662.
  6. United States Food and Drug Administration. (2018). Additional Information about High-Intensity Sweeteners Permitted for Use in Food in the United States. Retrieved from https://www.fda.gov/food/food-additives-petitions/additional-information-about-high-intensity-sweeteners-permitted-use-food-united-states
  7. European Food Safety Authority. (2011). Scientific Opinion on the re-evaluation of sucralose (E 955) as a food additive. EFSA Journal, 9(4), 1-67.

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