Artificial Sweeteners &Nonalcoholic Fatty Liver Disease

5.1. Artificial Sweeteners and Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a severe complication of obesity, which may present even in childhood. NAFLD is a condition where

 fat accumulates in the liver, due to the

 disruption of de novo lipogenesis (DNL), fatty acid β-oxidation, fatty acid uptake, and 

very-low-density lipoprotein (VLDL) synthesis and secretion mechanisms in the liver [91]. 

Experimental studies in mice have revealed the association between consumption of 

artificially sweetened beverages and

 the development of NAFLD [92]. Also, a recent study that included adults from the U.S. identified a relationship between the consumption of

 AS beverages and the risk of NAFLD development [93]. Furthermore, another paper that included four European studies showed that the consumption

 of low/no-calorie beverages is associated with NAFLD [94]. Inversely, a systematic review and meta-analysis of seven observational studies reported that there is no clear connection between the consumption of artificially sweetened beverages (ASBs) and NAFLD due to insufficient studies in human subjects [95].

Sucralose is the most studied NNS for possible deleterious effects on the liver. Sucralose exerts its effect through various mechanisms, such as the stimulation of hepatic proinflammatory cytokines, the promotion of hepatic lymphocytic infiltration, and the increased hepatic lipogenesis [96,97]. Additionally, sucralose activates the T1R3-ROS-ER stress-dependent pathway [98]. The activation of T1R3 generates reactive oxygen species and triggers lipolysis and endoplasmic reticulum (ER) stress in the liver. ER stress stimulates the production of lipid droplets and interferes with very-low-density lipoprotein (VLDL) metabolism, both enhancing VLDL delivery to hepatocytes and inhibiting VLDL synthesis and export from these cells, which in turn triggers intracellular triglyceride accumulation, which favors the development of NAFLD [99,100]. ER stress also promotes apoptosis and reduces autophagy in the liver, which is connected to the development of NAFLD in mice [101]. In addition, sucralose alters the composition of gut microbiota, thus promoting the production of bile acids that have a proinflammatory effect on hepatocytes [102]. Hence, in order to elucidate any possible association between NNSs and NFALD, longer-term prospective studies in children and adults with objective methods measuring the intake of sweeteners are needed.

Regarding natural sweeteners’ effects on adipogenesis, there are very limited previous studies. Kakleas et al. [21] reported that stevia and trehalose may have a protective effect on NAFLD. An experimental study in db/db mice hepatocytes showed that stevia and stevioside attenuated liver steatosis through the mechanism of PPARa-mediated lipophagy [103].

Thus, most previous studies showed that AS consumption is associated with the development of NAFLD, whereas natural sweeteners, such as stevia, may have a protective effect on NAFLD. Further studies are necessary 

to elucidate these findings

Ref

Nutrients. 2024 Sep 19;16(18):3162. doi: 10.3390/nu16183162

Chronic Use of Artificial Sweeteners: Pros and Cons

Lydia Kossiva 1, Kostas Kakleas 2, Foteini Christodouli 1, Alexandra Soldatou 1, Spyridon Karanasios 1, Kyriaki Karavanaki 1,*

Editor: Xiaohua Pan