New study suggests that increased dietary intake of fructose (fruit sugar) may have negative effect on immunity. This further adds reason to caution dietary intake of fructose, with regard to its effects on the immune system.
Fructose is a simple sugar found in many sources such as fruits, table sugar, honey and most types of syrup. Fructose intake has shown a steady increase, mainly attributed due to consumption of high amounts of high fructose corn syrup, especially in the Western countries. Fructose is known to be associated with obesity, type 2 diabetes and non-alcoholic fatty liver disease1. This is likely due to fructose in the body undergoing different metabolic pathways compared to glucose and which are less regulated than those of glucose; this is believed to lead to an increase in the synthesis of fatty acids leading to negative health outcomes2. Also, anecdotally, humans are more “used to” and adapted to glucose which may suggest poorer handling of fructose.
A recent study shows the mechanisms by which fructose causes dysfunctions in immune cells1. This research explores the effects of fructose on the immune cells, especially monocytes. Monocytes protect humans from microbial invasion and are part of the innate immune system3. The innate immune system prevents pathogens invading the body4. The negative consequences of fructose on immune cells expands the list of well described negative health consequences of fructose, suggesting that dietary fructose consumption may also not be conducive for optimal immune health. However, it is important to state that fructose and fruit are not interchangeable as many fructose sources such as high fructose corn syrup have no useful nutrients, and that there may be certain benefits of consuming specific fruits such as fibre and micronutrient intake which may outweigh the risks of the associated fructose.
Monocytes treated with fructose showed such low levels of glycolysis (a metabolic pathway which derives energy for cells to use) that levels of glycolysis from fructose were almost equivalent to glycolysis in cells treated with no sugar at all1. Furthermore, monocytes treated with fructose had higher levels of oxygen consumption (and therefore demand) than monocytes treated with glucose1. Fructose-cultured monocytes also had a higher dependence on oxidative phosphorylation than glucose-cultured monocytes1. Oxidative phosphorylation generates oxidative stress via the creation of free radicals5.
Fructose-treated monocytes displayed a lack of metabolic adaptation1. Fructose-treatment also increased inflammatory markers such as interleukins and tumour necrosis factor significantly more than glucose-treatment1. This is supported by the finding that dietary fructose increases inflammation in mice1. Furthermore, fructose-treated monocytes were not metabolically flexible and depended on oxidative metabolism for energy1. However, T-cells (another immune cell) were not affected negatively by fructose in terms of inflammatory markers, but fructose is known to contribute to diseases such as obesity, cancer and non-alcoholic fatty liver disease and this new finding expands the list of potential harms of fructose by causing negative effects on the immune system1. This new research also shows the oxidative-stress effects and inflammatory effects of fructose and suggests the vulnerability of the important immune cells: monocytes, when using fructose for energy1. Therefore, this study further adds reason to caution dietary intake of fructose, with regard to its effects on the immune system.
- B Jones, N., Blagih, J., Zani, F. et al. Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation. Nat Commun 12, 1209 (2021). https://doi.org/10.1038/s41467-021-21461-4
- Sun, S.Z., Empie, M.W. Fructose metabolism in humans – what isotopic tracer studies tell us. Nutr Metab (Lond) 9, 89 (2012). https://doi.org/10.1186/1743-7075-9-89
- Karlmark, K. R., Tacke, F., & Dunay, I. R. (2012). Monocytes in health and disease – Minireview. European journal of microbiology & immunology, 2(2), 97–102. https://doi.org/10.1556/EuJMI.2.2012.2.1
- Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Innate Immunity. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26846/
- Speakman J., 2003. Oxidative phosphorylation, mitochondrial proton cycling, free-radical production and aging. Advances in Cell Aging and Gerontology. Volume 14, 2003, Pages 35-68. DOI: https://doi.org/10.1016/S1566-3124(03)14003-5