What is Fructose?

What is Fructose? Fructose is a type of sugar present in fruits that is also often added to processed foods and beverages. However, consuming too much fructose can have harmful effects on the liver, the organ that metabolizes most of the fructose we eat. Studies have shown that high fructose intake can cause toxicity such as fatty liver disease, inflammation, and even liver cancer.

Liver Toxicity

Fructose has been implicated in liver toxicity and the development of metabolic disorders. Indeed, fructose can cause liver ATP depletion (lack of energy) and lipogenesis (fat creation), as it bypasses the key regulated step of glycolysis (sugar destruction to obtain energy) (Jang et al., 2018).

Fructose metabolism in the liver can lead to the accumulation of special sugars, which can cause toxicity to the liver and contribute to liver damage (Ishimoto et al., 2012). Diets containing high quantity of fructose have been shown to induce more damage in the liver and mitochondria compared to diets containing only high fat (García-Berumen et al., 2019). Researchers confirm that fructose-rich diets can cause damage to hepatic mitochondrial integrity and impair mtDNA repair and replication mechanisms, leading to liver toxicity and dysfunction (Cioffi et al., 2017).

Inflammation

Inflammation is a natural defence mechanism that helps the body fight infections and injuries. However, chronic inflammation can damage healthy tissues and organs. Fructose can cause inflammation in the liver by activating immune cells called macrophages, which release pro-inflammatory signalling proteins (Handayani et al., 2021). These proteins can also stimulate the growth of fibrous tissue and scar tissue in the liver, which can reduce blood flow and oxygen delivery to the liver cells, which again reinforces the inflammation process.

The detrimental effects of high fructose on the liver include insulin resistance, enhanced lipogenesis, non-alcoholic fatty liver disease (NAFLD) that is cirrhosis, non-alcoholic steatohepatitis (NASH), and type 2 diabetes (Mai & Yan, 2019). High fructose intake has been associated with increased liver steatosis and inflammation. Fructose can also activate human hepatic stellate cells, which are involved in liver fibrosis (Shakerian et al., 2020). Excessive intake of fructose has been linked to the increasing incidence of non-alcoholic fatty liver, obesity, and diabetes, known to be other forms of systemic inflammation (Xie et al., 2022). It has been shown that fructose disturbs key metabolic pathways in the liver, leading to negative effects on insulin sensitivity, blood pressure, and liver metabolism (Robubi et al., 2014).

Fatty Liver

Fatty liver disease occurs when excess fat accumulates in the liver cells. This can impair the liver’s function and lead to complications such as cirrhosis and liver failure (Bu et al., 2018). Fructose can promote fatty liver disease by damaging the intestinal barrier, which normally prevents bacteria and toxins from entering the bloodstream. As a matter of fact, fructose consumption has been reported to promote liver fibrosis in fatty liver disease and to be associated with fibrosis severity in NAFLD patients (Liu et al., 2018). When the intestinal barrier is compromised, endotoxins from bacteria can trigger an inflammatory response in the liver and increase the production of enzymes that convert fructose into fat.

Liver Cancer

Liver cancer is a serious condition that can be fatal if not detected and treated early. Fructose can increase the risk of liver cancer by inducing oxidative stress, which is an imbalance between free radicals and antioxidants in the body (Keshari et al., 2009). Free radicals are unstable molecules that can damage DNA and cause mutations. Antioxidants are molecules that can neutralize free radicals and protect cells from oxidative damage. Fructose can deplete antioxidants and increase free radicals in the liver, which can lead to DNA damage and cancer formation. Consequently, fructose studies have shown the link between fructose and proinflammatory, fibrogenic, and oncogenic signalling pathways in the liver, which contribute to its deleterious effects and the development of liver cancer (Muriel et al., 2021).

Conclusions

What is Fructose, again? Fructose is not a harmless sugar. It can have toxic effects on the liver and contribute to various diseases. The toxicity of fructose is linked to its necessary liver metabolism. fructose consumption has been linked to the development of fatty liver and liver cancer. It can disrupt normal liver homeostasis, enhance liver fibrosis, and activate oncogenic signaling pathways. Further research is needed to fully understand the mechanisms underlying the detrimental effects of fructose on liver health and its role in liver cancer development. Therefore, it is important to limit fructose intake and choose healthier sources of carbohydrates such as seeds, vegetables, and proteins (meat, fish, and eggs).

Please Visit our YouTube Channel and Subscribe

References - What is Fructose

Bu, P., Chen, K., Xiang, K., Johnson, C., Crown, S. B., Rakhilin, N., … & Shen, X. (2018). Aldolase B-mediated Fructose Metabolism Drives Metabolic Reprogramming Of Colon Cancer Liver Metastasis. Cell Metabolism, 6(27), 1249-1262.e4. https://doi.org/10.1016/j.cmet.2018.04.003

Cioffi, F., Senese, R., Lasala, P., Ziello, A., Mazzoli, A., Crescenzo, R., … & Iossa, S. (2017). Fructose-rich Diet Affects Mitochondrial Dna Damage and Repair In Rats. Nutrients, 4(9), 323. https://doi.org/10.3390/nu9040323

García-Berumen, C. I., Ortiz-Avila, O., Vargas-Vargas, M., Rosario-Tamayo, B. A. d., Guajardo-López, C., Saavedra-Molina, A., … & Cortés-Rojo, C. (2019). The Severity Of Rat Liver Injury By Fructose and High Fat Depends On The Degree Of Respiratory Dysfunction And Oxidative Stress Induced In Mitochondria. Lipids Health Dis, 1(18). https://doi.org/10.1186/s12944-019-1024-5

Handayani, D., Febrianingsih, E., Kurniawati, A. D., Kusumastuty, I., Nurmalitasari, S., Widyanto, R. M., … & Sulistyowati, E. (2021). High-fructose Diet Initially Promotes Increased Aortic Wall Thickness, Liver Steatosis, and Cardiac Histopathology Deterioration, But Does Not Increase Body Fat Index. Journal of Public Health Research, 2(10), jphr.2021.2181. https://doi.org/10.4081/jphr.2021.2181

Ishimoto, T., Lanaspa, M. A., Le, M. T., Garcia, G. E., Diggle, C. P., MacLean, P. S., … & Johnson, R. J. (2012). Opposing Effects Of Fructokinase C and A Isoforms On Fructose-induced Metabolic Syndrome In Mice. Proc. Natl. Acad. Sci. U.S.A., 11(109), 4320-4325. https://doi.org/10.1073/pnas.1119908109

Jang, C., Hui, S., Lu, W., Cowan, A., Morscher, R., Lee, G., … & Rabinowitz, J. (2018). The Small Intestine Converts Dietary Fructose Into Glucose and Organic Acids. Cell Metabolism, 2(27), 351-361.e3. https://doi.org/10.1016/j.cmet.2017.12.016

Keshari, K. R., Wilson, D., Chen, A. P., Bok, R., Larson, P. E. Z., Hu, S., … & Kurhanewicz, J. (2009). Hyperpolarized [2-13c]-fructose: a Hemiketal Dnp Substrate For In Vivo Metabolic Imaging. J. Am. Chem. Soc., 48(131), 17591-17596. https://doi.org/10.1021/ja9049355

Liu, J., Jiang, S., Zhao, Y., Sun, Q., Zhang, J., Shen, D., … & Li, C. (2018). Geranylgeranyl Diphosphate Synthase (Ggpps) Regulates Non-alcoholic Fatty Liver Disease (Nafld)-fibrosis Progression By Determining Hepatic Glucose/fatty Acid Preference Under High-fat Diet Conditions. J. Pathol., 3(246), 277-288. https://doi.org/10.1002/path.5131

Muriel, P., López-Sánchez, P., Ramos-Tovar, E. (2021). Fructose and The Liver. IJMS, 13(22), 6969. https://doi.org/10.3390/ijms22136969

Shakerian, E., Yaghooti, H., Kheirollah, A., Mohammadtaghvaei, N. (2020). Effect Of High Concentrations Of Fructose On the Expression Of Tgf-β And α-Sma Genes In Human Hepatic Stellate Cells. Jentashapir J Cell Mol Biol, 3(11). https://doi.org/10.5812/jjcmb.110136

Xie, J., Shi, S., Liu, Y., Wang, S., Rajput, S. A., Song, T. (2022). Fructose Metabolism and Its Role In Pig Production: A Mini-review. Front. Nutr., (9). https://doi.org/10.3389/fnut.2022.922051