Intestinal Metabolism and Bioaccumulation of Sucralose In Adipose Tissue In The Rat

Abstract

The aim of this study was to (1) determine if the organochlorine artificial sweetener sucralose is metabolized in rat intestine with repeated dosing and (2) examine whether sucralose might bioaccumulate in rat adipose tissue. Sucralose was administered to 10 rats by gavage daily for 40 days at an average dosage of 80.4 mg/kg/day. The dosages were within the range utilized in historical toxicology studies submitted for regulatory approval in North America, Europe, and Asia. Feces and urine were collected individually from each animal for every 24-hr period during the 40day dosing period. Analysis of the urine and fecal extracts by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) revealed two new biotransformation products that have not previously been reported. These two metabolites are both acetylated forms of sucralose that are less polar and hence more lipophilic than sucralose itself. These metabolites were present in urine and feces throughout the sucralose dosing period and still detected at low levels in the urine 11 days after discontinuation of sucralose administration and 6 days after sucralose was no longer detected in the urine or feces. The finding of acetylated sucralose metabolites in urine and feces do not support early metabolism studies, on which regulatory approval was based, that claimed ingested sucralose is excreted unchanged (i.e. not metabolized). The historical metabolic studies apparently failed to detect these metabolites in part because investigators used a methanol fraction from feces for analysis along with thin layer chromatography and a low-resolution linear radioactivity analyzer. Further, sucralose was found in adipose tissue in rats two weeks after cessation of the 40-day feeding period even though this compound had disappeared from the urine and feces. Thus, depuration of sucralose which accumulated in fatty tissue requires an extended period of time after discontinuation of chemical ingestion. These new findings of metabolism of sucralose in the gastrointestinal tract (GIT) and its accumulation in adipose tissue were not part of the original regulatory decision process for this agent and indicate that it now may be time to revisit the safety and regulatory status of this organochlorine artificial sweetener ARTICLE HISTORY

Natural and Artificial Sweeteners and High Fat Diet Modify Differential Taste Receptors, Insulin, and TLR4-Mediated Inflammatory Pathways in Adipose Tissues of Rats

“…It is important to point out that even low sucralose concentration (1.5%), used in this study, showed similar effects than 10% sucrose. These results could be in part due to the fact that sucralose is metabolized in rats to compounds that are less polar and more lipophilic than the parent compound and persisted in adipose tissue two weeks after cessation of use [5]. L cells of the gut contain taste receptors that modulate GLP1 secretion in the gut and may play an important role in the development of obesity, diabetes, and changes in gut motility [19].…”

“…However, in the recent years, controversial results have been reported about the consumption of artificial sweeteners that have been associated with a greater risk of being overweight or obese [3]. Besides that, other studies have focused on other monosaccharides, particularly fructose [4], and few studies have focused on other natural complex sweeteners, such as honey, brown sugar, steviol glycosides, or the artificial sweetener sucralose [5]. In conditions of persistent intake of sweeteners, some taste receptors type 1 member 2 (T1R2) or member 3 (T1R3) are activated in tongue, intestine, and adipose tissue [6,7,8].…”

Consumption of Diet Soda Sweetened with Sucralose and Acesulfame‐Potassium Alters Inflammatory Transcriptome Pathways in Females with Overweight and Obesity

“…Indeed, recent studies in rats reveal that sucralose accumulates in adipose tissue and can be detected in adipocytes, urine, and feces 2 weeks after the rats stop receiving sucralose. [ 18 ] These findings and our present in vivo results in humans are particularly noteworthy because adipose tissue is central to whole body metabolism and adipose‐derived immune molecules, such as inflammatory cytokines, are highly expressed in obese individuals. [ 19 ] The contribution of inflammation to the pathogenesis of obesity‐associated cardiometabolic diseases, such as type 2 diabetes (T2D) and cardiovascular disease (CVD) is well‐established.…”

Biological Responses to the Consumption of Non-Nutritional Sweeteners

“…Sugar alcohols can also reach the colonic microbiota and act as prebiotics, with accompanying negative laxative effects [67], particularly in patients with inflammatory bowel syndrome (IBS). Since sucralose can deposit in fat tissue in an acelatyed version (see metabolism section), studies that have looked at the effect of sucralose with less than a week washout period could have to be revisited [68].…”