5.3 Artificial Sweeteners &,
Insulin Resistance
Prolonged use of artificial sweeteners by healthy
individuals may be associated with the development of insulin resistance and T2DM [104,105] or
the deterioration of glycemic control in patients with diabetes [64]. This seemingly paradoxical association between artificial sweeteners consumption and metabolic disorders has been epidemiologically
observed and explained by the following hypotheses.
One hypothesis is based on the suppression
of the cephalic phase of digestion by the sweet taste
artificial sweeteners [106]. Consumption of artificial sweeteners by mice led to hyperglycemic responses to oral glucose load combined with decreased levels of circulating GLP-1. This was not observed when glucose was infused directly into the stomach, suggesting that altered glucose homeostasis is related to the response to the sweet taste [107].
A second hypothesis supports that consuming artificial sweetener affects the gut microbiota. Artificial sweeteners, such as saccharin, sucralose, aspartame and stevia, resist fermentation by oral bacteria and have bacteriostatic activity [108,109]. They have similar effects on the gut microbiota in both animals and humans [75], impairing digestion and glucose homeostasis.
The third hypothesis supports that sweet taste receptors, including T1R (taste receptor one) and a-gustducin, respond to both caloric sugars, such as sucrose and glucose, and to artificial sweeteners, such as sucralose and acesulfame-k [110,111]. These receptors are also found in the intestinal mucosal secretory L cells, which secrete the peptide GLP-1 [112] and promote insulin excretion. The effect of NNSs on insulin sensitivity can be explained by activation of taste receptor type 1 member 3 (T1R3) and extracellular signal-regulated kinase (ERK1/2) signaling pathway [113]. Studies in mice have revealed that sucralose, through the activation of T1R3, generates reactive oxygen species and triggers lipolysis and endoplasmic reticulum stress in the liver [114]. Endoplasmic reticulum stress results in increased production of proinflammatory cytokines, such as TNF-α and interleukin 6, which further exacerbate inflammation, increase cortisol levels, and promote insulin resistance via the disruption of the insulin signaling pathway [115,116]. Furthermore, studies in trophoblasts treated with aspartame have exhibited cessation of cell proliferation due to increased oxidative stress [117]. Activation of the ERK1/2 pathway in hepatic cells results in decreased expression of adiponectin and increased lipolysis [113]. Consequently, the released free fatty acids from lipolysis can promote the expression of inflammatory cytokines and provoke an inflammatory response, contributing to the development of insulin resistance [118].
Studies in mice also suggest that AS consumption affects the absorption of glucose from the intestinal lumen cells by increasing the expression of the glucose transporter SGLT1 (sodium-dependent glucose transporter isoform 1) and GLUT2 (apical glucose transporter 2) [119,120].
On the other hand, a possible favorable effect of natural sweeteners on glucose metabolism has been reported in animal studies [121]. Specifically, moderate intake of hoodia decreased insulin resistance and inflammatory markers levels [122]. Although the underlying mechanism is still unclear, studies suggest an antidiabetic effect of stevia [123]. In particular, the phenols contained in the leaves of stevia—about 91 mg/g—are the main contributors to the antihyperglycemic activity. Indeed, the leaves of stevia have an antioxidative action, with the highest benefit being found in rats with diabetes [124].
Since only the last two mechanisms have been evaluated in humans, and existing studies’ methodologies vary, further research is needed to determine underlying pathophysiological mechanisms.
Thus, from the above studies, it is concluded that artificial sweeteners use is associated with the development of insulin resistance and T2DM, while, oppositely, natural sweeteners seem to decrease insulin resistance and may be beneficial for chronic use by patients with diabetes
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
No comments:
Post a Comment