March 15, 2023

expert reaction to study of high sucralose diet and immune response in mice

A study published in Nature looks at the dietary sweetener sucralose and immune response in mice.

Prof Neil Mabbott, Personal Chair in Immunopathology at the Roslin Institute, University of Edinburgh, said:

“This is an interesting study which revealed how prolonged consumption of high doses of the artificial sweetener sucralose can affect the activities of a specific type of T cells in the immune system.  The authors show that feeding mice high doses of sucralose reduced the abilities of their CD8 T cells to respond to tumours and to protect against infection with Listeria monocytogenes bacteria. 

“It is important to note that this study does not suggest that consumption of sucralose will similarly suppress the immune system in humans.  The mice in this study were continually provided for several weeks with much higher levels of sucralose than would typically be reached when used as a dietary sugar substitute.  Reassuringly, the study suggested that these effects may be reversible as the negative effects on the T cell responses began to recover when the sucralose treatment was stopped. 

“Despite these limitations, the study also showed that the effects of high doses of sucralose on T cells delayed the development the autoimmune disease type-1 diabetes.  Further research on how sucralose affects T cell function may identify new methods to treat certain T cell-related autoimmune diseases such as type-1 diabetes.”

Prof Daniel Davis, Head of the Department of Life Sciences at Imperial College London, said:

“This paper is hugely important in showing that sucralose is not a molecule which simply has no action in the human body, as might have been assumed. At high doses, it can lower the ability of T cells to play their part in our immune response. There is evidence that it can do this by subtly changing the normal organisation of molecules in the surface of T cells. Other work has suggested changes in the microbiome can be caused by sucralose but that’s not shown to be important here.

“Overall, this is an important paper for science but much more research is needed to know the importance of this in our everyday lives. The research here focusses on mice and uses experiments designed to highlight any changes in T cell responsiveness. Whether any effects would be seen in human immune reactions to actual infections or in other disease settings remains to be tested. Also, the dose of sucralose used here to affect T cells is achievable in human blood but very high. The effect was reversible, so if further work shows any effects in human health, this would likely be prevented by a change in diet. It is also important that effects were specific to sucralose, and not seen with other sweeteners. Although scientists often say this, my overall view is that more research is sorely needed.”

The following comment was provided by our colleagues at SMC Spain:

Prof África González Fernández, Professor of Immunology, Director of the Centro de Investigaciones Biomédicas (CINBIO) and former president of the Spanish Society of Immunology (SEI), said:

“The study has to be considered with great caution. I notice several elements that I think should be taken into account.

“I find the title misleading, as it implies that sucralose has negative effects on the T-cell immune response, when what has been studied are very high doses—much higher than those of a typical human diet.

“We should keep in mind that the animals in the study did not show any alteration in their immune components, and most of the findings were in in vitro cells cultures.

“On the other hand, I find that the article lacks studies of the immune response against pathogens such as viruses, for example, where the cellular immune response is essential – together with that of B lymphocytes, which differentiate into antibody-producing plasma cells. Instead, the authors have focused on tumour and autoimmunity models.

“They have not determined potential mechanisms underlying this specific effect on T-cells and their cell membranes. This is an avenue worth exploring.

“The novelty that this study brings is very debatable, considering that the study design uses much higher doses than those of a normal human diet, so the practical implications in terms of the human diet are very limited. Everything, absolutely everything, can be toxic in certain doses. The results obtained with such high doses show an exclusive effect on T-cells in specific animal models, with a decrease in the anti-tumoral response and a potentially beneficial effect on autoimmunity (the researchers tested a model of diabetes).

“The study therefore has many limitations. The dose used, which is not physiological; the fact that it is an animal model (mouse); the time of administration, and the fact that the tests are in vitro.

“I believe that these data should be taken with great caution and not be extrapolated directly to what might happen in humans. There are hundreds of studies carried out with this substance and, except for changes in the microbiota, it has not been shown to cause any problems for human health. It is safe, non-carcinogenic and does not affect the immune system.”

‘The dietary sweetener sucralose is a negative modulator of T cell-mediated responses’ by Fabio Zani et al. was published in Nature at 4pm UK time on Wednesday 15 March 2023.

DOI: https://doi.org/10.1038/s41586-023-05801-6

Declared interests

Prof Neil Mabbott: “I have no competing conflicts of interest to declare.”

Prof Daniel Davis: “I am the author of books about the immune system – The Beautiful Cure and The Secret Body.”

Prof África González Fernandez: “I have no conflict of interest. I am a co-cofounder of the company NanoImmunotech, which is not related to this research area”.