![]() ![]() CFSE, carboxyfluorescein succinimidyl ester. b, Circulating Scrl levels in mice given water containing different Scrl concentrations for 2 weeks. Scrl concentrations are indicated in mg ml −1 throughout. Dashed lines indicate the BSA-adjusted EFSA (black) and FDA (purple) maximum ADI. In box plots, whiskers show the minimum and maximum values, box margins represent the first and third quartile and the central line is the median value. 1a), reaching a plasma concentration of around 1 µM at the highest dose of sucralose, consistent with the levels that can be achieved in humans 8.Ī, Sucralose (Scrl) intake in mice given 0.72 mg ml −1 (blue n = 6) or 0.17 mg ml −1 (aquamarine n = 6) Scrl. As expected, we were able to detect increasing amounts of circulating sucralose corresponding with increased consumption in mice (Fig. By allowing mice ad libitum access to water containing 0.72 mg ml −1 or 0.17 mg ml −1 of sucralose, we calculated-using BSA equivalents-that the consumption of sucralose over 10 weeks was near the equivalent of the ADI recommended by either EFSA (at the 0.72 mg ml −1 dose) or FDA (at the 0.17 mg ml −1 dose) (Fig. Allometric scaling on the basis of body surface area (BSA) equivalents can be used to convert human doses of drugs to mouse doses by adjusting for the increased metabolic rate in mice 9. 8). The maximum acceptable daily intake (ADI) of sucralose for humans has been established as 15 mg per kg (body weight) by the European Food Safety Authority (EFSA) or 5 mg per kg (body weight) by the US Food and Drug Administration (FDA). Despite its limited absorption 7, circulating sucralose can be detected in humans following consumption of sucralose-containing food or drinks 8, with consumption of 250 mg sucralose resulting in plasma sucralose levels of around 1 μM within 90–120 min (ref. Sucralose is a commonly used, calorie-free sweetener that is about 600 times sweeter than sucrose 6. Overall, these findings suggest that a high intake of sucralose can dampen T cell-mediated responses, an effect that could be used in therapy to mitigate T cell-dependent autoimmune disorders. Mice given sucralose show decreased CD8 + T cell antigen-specific responses in subcutaneous cancer models and bacterial infection models, and reduced T cell function in models of T cell-mediated autoimmunity. Mechanistically, sucralose affects the membrane order of T cells, accompanied by a reduced efficiency of T cell receptor signalling and intracellular calcium mobilization. In this study, we show that the intake of high doses of sucralose in mice results in immunomodulatory effects by limiting T cell proliferation and T cell differentiation. Although generally regarded as safe, some concerns have been raised about the long-term safety of the consumption of certain sweeteners 2, 3, 4, 5. Artificial sweeteners are used as calorie-free sugar substitutes in many food products and their consumption has increased substantially over the past years 1. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |