Human Immune Cells React to Non-Nutritive Sweeteners

Research |

Non-nutritivesweeteners are sweeteners that have very high sweetening power but contribute little or nothing to energy intake. They play a major role not only in the U.S. but also in Germany - especially among people who love sweets but want to cut calories and sugar.

Scientist analyzes cells using a flow cytometer
Scientist analyzes cells using a flow cytometer/Photo: C. Schranner/Leibniz-LSB@TUM
Working in the cell culture lab
Working in the cell culture lab/Photo: J. Krpelan/Leibniz-LSB@TUM

Diet drinks often contain a mix of non-nutritive sweeteners that also enter the bloodstream after consumption. As a new pilot study shows, even dietary intake levels of saccharin, acesulfame-K and cyclamate are enough to modulate the copy rate of various genes in white blood cells. "Our data suggest that this modulation sensitizes immune cells to certain immune stimuli," says Dietmar Krautwurst of the Leibniz Institute for Food Systems Biology at the Technical University of Munich. He adds: “Likewise, they also suggest that taste receptors may act as sweetener sensors of the cellular immune system.”

Sweeteners don't just affect taste buds

However, sweeteners do not only affect the taste buds in the mouth. Recent studies suggest that they also affect the human immune system, although the underlying molecular relationships are still poorly understood. In order to contribute to their clarification, Dietmar Krautwurst's team was involved in a pilot study with ten healthy test subjects as part of a cooperation with the ZIEL - Institute for Food & Health at the Technical University of Munich.

At the beginning of the study, the participants had to drink 10.7 ml of a sweetener solution per kg of their body weight. The solution contained a beverage-typical mix of approx. 76 mg saccharin, 228 mg cyclamate and 53 mg acesulfame-K per liter. Converted to a 70 kg person, this resulted in a drinking volume of approximately 0.75 liters. The amounts of saccharin, cyclamate and acesulfame K consumed corresponded to approximately 16, 35, and 6 percent, respectively, of the acceptable daily sweetener intake according to the to the European Food Safety Authority (EFSA).

Subsequent blood analyses showed that four hours after drinking the test solution, sweetener concentrations in the blood were at their highest. The team therefore investigated, on the one hand, how the maximum concentrations of the respective sweeteners determined act in vitro on white blood cells, which serve the bacterial defense. On the other hand, the team analyzed ex vivo immune cells taken from the blood of the test subjects before and after the intervention.

Sweeteners influence the transcription of various genes

Both in vitro and in vivo, sweetener administration increased the copy rate of genes containing the blueprint of taste receptors that also commonly respond to sweeteners in the mouth. In addition, the sweeteners modulated the copy profile of genes encoding regulatory proteins of the immune system. According to the team, this does not necessarily lead to altered cell functions. Nevertheless, further study results suggested that the modulated transcriptional profile shifts cells into a state that makes at least isolated immune cells more sensitive to a bacterial stimulus in the presence of the three sweeteners.

"Our results suggest that even an average non-nutritive sweetener intake can affect immune cells in the blood. Of course, we cannot say at this stage whether this is good or bad for health. Further research is needed on this. However, we can deduce from our results the hypothesis that taste receptors serve as sensors for food-related stimuli not only in the mouth, but also on immune cells," explains Dietmar Krautwurst. The Leibniz Institute in Freising will further investigate this assumption.

Skurk, T., Krämer, T., Marcinek, P., Malki, A., Lang, R., Dunkel, A., Krautwurst, T., Hofmann, T.F., and Krautwurst, D. (2023). Sweetener system intervention shifted neutrophils from homeostasis to priming. Nutrients 15, 1260. 10.3390/nu15051260.

The work was funded by a grant of the German Ministry for Education and Research (BMBF) FK#01EA1409A. The preparation of this paper was supported by the enable cluster and is catalogued by the enable Steering Committee as enable 060 (, accessed on 27 February 2023). Tiffany Krautwurst was supported by an ERASMUS fellowship (#403/151201-1) from the Technical University of Munich.

More information:

Sweetener concentrations used in the culture medium of isolated immune cells:

0.7 micromoles/L saccharin; 0.3 micromoles/L acesulfame-K; and 1.0 micromoles/L cyclamate.

ADI values for sweeteners:

Acceptable Daily Intake (ADI) levels were derived for each of the sweeteners in the health assessment:

Why sweetener blends?

Beverage manufacturers use mixtures of non-nutritive sweeteners for taste reasons. This keeps the concentration of the individual sweeteners low, which reduces the occurrence of bitter off-flavors. In contrast to sugar, in high concentrations non-nutritive sweeteners often taste less sweet and also bitter, since in high doses they inhibit the sweet taste receptor and activate some bitter taste receptor types as well. In addition, saccharin and cyclamate, for example, positively influence each other's taste perception.

Sweetener per capita consumption:

Annual per capita consumption of sweeteners in the U.S. averages 80 to 90 grams. In contrast, according to Statista, the average annual consumption in Germany this year is expected to be only 50 grams per person:

General information on non-nutritive sweeteners approved in the EU:


Scientific contact:
PD Dr. Dietmar Krautwurst
Leibniz Institute for Food Systems Biology at TUM
Lise-Meitner-Str. 34
85354 Freising
Tel. +49 8161 71 2634

Dr. Gisela Olias
Leibniz Institute for Food Systems Biology at TUM