Sucralose (SPLENDA®) Toxicity - the Scientific Reports

The dietary sweetener sucralose is a negative modulator of T cell-mediated responses - HERE

Nature, Vol 615, 2023

...Overall, these findings suggest that a high intake of sucralose can dampen T cell-mediated responses, an effect that could be used in therapy to mitigate T cell-dependent autoimmune disorders...

Sucralose promotes accumulation of reactive oxygen species (ROS) and adipogenesis in mesenchymal stromal cells - HERE

Stem Cell Research & Therapy ( IF 4.627 ) Pub Date : 2020-06-26 

... Increased ROS accumulation was observed within 72 h of exposure. Increased adipogenesis was also noted when exposed to higher dose of sucralose. Sucralose promotes ROS accumulation and adipogenesis in human adipose tissue derived mesenchymal stromal cells.

(ROS can decrease an organism's fitness because oxidative damage is a contributor to senescence. In particular, the accumulation of oxidative damage may lead to cognitive dysfunction) admin emphasis.

Sucralose vs Sucrose on Appetite and Reward Processing A Randomized Crossover Trial - HERE

JAMA Netw Open. 2021;4(9):e2126313. doi:10.1001/jamanetworkopen.2021.26313

Question  Are adiposity and sex associated with neural, metabolic, and behavioral responses to consumption of nonnutritive sweeteners (NNSs) vs nutritive sugar?

Meaning  These findings suggest that female individuals and those with obesity have greater neural reward responses to NNS vs nutritive sugar consumption, highlighting the need to consider individual biological factors that might influence the efficacy of NNS.

CSPI downgrades sucralose from "caution" to "avoid" - HERE

Center for Science in the Public Interest, February 8, 2016

... The Center for Science in the Public Interest has downgraded its safety rating of sucralose, the artificial sweetener also known by the brand name Splenda, from “caution” to “avoid” in the group’s Chemical Cuisine glossary of food additives. ...

Migraine Triggered by Sucralose--A Case Report - HERE

Headache | 2006 Mar;46(3):515-7.

Abstract
Sucralose is the active compound of the most commonly sold sweetener in the United States. Different than aspartame, sucralose is not considered to be a migraine trigger. Herein we report a patient with attacks of migraine consistently triggered by sucralose. She also suffers from menstrually related migraine that had been well-controlled for several months since she switched her contraceptive from fixed estrogen to triphasic contraceptive pills. Some attacks triggered by sucralose were preceded by aura, and she had never experienced migraine with aura before. Withdrawal of the compound was associated with complete resolution of the attacks. Single-blind exposure (vs. sugar) triggered the attacks, after an attack-free period.

Migraine Triggered by Sucralose—A Case Report (includes downloadable pdf) HERE

April 2006. Headache The Journal of Head and Face Pain 46(3):515-7

... Herein we report the case of a migraineur with attacks consistently triggered by a sweetener containing sucralose. The trigger was identified using headache calendars and trigger questionnaires, and confirmed by prospective singleblinded challenge. ...

Polychlorinated dibenzo-p-dioxins and dibenzofurans formed  from sucralose at high temperatures - HERE

Sci Rep. 2013; 3: 2946. Published online 2013 Oct 15. 

... Our data indicate that sucralose may produce significant amounts of PCDD/Fs when heated in stainless steel utensils or in metal utensils in the presence of rust (Al2O3, Fe2O3, or CuO) at high temperatures. Occupational exposure to PCDD/Fs has attracted concern 27. The improper use of sucralose at high temperatures may result in human exposure to PCDD/Fs. ...

Plasma concentrations of sucralose in children and adults - HERE

Toxicol Environ Chem. 2017; 99(3): 535–542. Published online 2016 Oct 17

... Due to their lower body weight and blood volume, children have markedly higher plasma sucralose concentrations after consumption of a typical diet soda, emphasizing the need to determine the clinical implications of sucralose use in children. ...

Pharmacokinetics of Sucralose and Acesulfame-Potassium in Breast Milk Following Ingestion of Diet Soda - HERE

J Pediatr Gastroenterol Nutr. 2018 Mar; 66(3): 466–470.

... Ace-K and sucralose transfer into breast milk following ingestion of a diet soda. Future research should measure concentrations after repeated exposure and determine whether chronic ingestion of sucralose and acesulfame-potassium via the breast milk has clinically relevant health consequences....

Popular Sweetner Sucralose as a Migraine Trigger - HERE

Headache The Journal of Head and Face Pain, 22 August 2006

... Sucralose (trichlorogalactosucrose, or better known as Splenda) is an artificial sweetener from native sucrose that was approved by the FDA on April 1, 1998 (April Fool's Day). This observation of a potential causal relationship between sucralose and migraines may be important for physicians to remember this can be a possible trigger during dietary history taking. Identifying further triggers for migraine headaches, in this case sucralose, may help alleviate some of the cost burden (through expensive medical therapy or missed work opportunity) as well as provide relief to migraineurs...

Sucralose, A Synthetic Organochlorine Sweetener: Overview Of Biological Issues (full report - no charge to read) HERE

Journal of Toxicology and Environmental Health, Part B Critical Reviews Volume 16, 2013 - Issue 7

... Cooking with sucralose at high temperatures was reported to generate chloropropanols, a potentially toxic class of compounds. Both human and rodent studies demonstrated that sucralose may alter glucose, insulin, and glucagon-like peptide 1 (GLP-1) levels. Taken together, these findings indicate that sucralose is not a biologically inert compound. ...

What made Canada become a country with the highest incidence of inflammatory bowel disease: Could sucralose be the culprit? (important document - full report) HERE

Can J Gastroenterol. 2011 Sep; 25(9): 511.

... As I suggested a decade ago, regarding the possible risk of saccharin on IBD (7), sucralose may have a similar but stronger impact on gut bacteria, digestive protease inactivation and gut barrier function. This may provide a possible explanation for the more pronounced high incidence of IBD observed in Canada. The use of sucralose is soaring, and is now being used in thousands of food products (10). Therefore, it would be worthwhile to investigate whether possible links between sucralose intake and IBD exist, before it is too late. ...

Sucralose decreases insulin sensitivity in healthy subjects:A randomized controlled trial (downloadable free pdf) - HERE

Article in American Journal of Clinical Nutrition · September 2018

... Sucralose may have effects on glucose metabolism, and our study complements findings previously reported in other trials. Further studies are needed to confirm the decrease in insulin sensitivity and to explore the mechanisms for these metabolic alterations. ...

The not-so-sweet effects of sucralose on blood sugar control - HERE

The American Journal of Clinical Nutrition, Volume 108, Issue 3, September 2018, Pages 431–432

... The findings in this homogeneous group of healthy, normal-weight adults, nonregular consumers of LCSs, might not extrapolate to adults with obesity or with diabetes, to children, or even to people who consume LCSs chronically, and additional studies are needed.  ...

A Single 48 mg Sucralose Sip Unbalances Monocyte Subpopulations and Stimulates Insulin Secretion in Healthy Young Adults - HERE

National Library of Medicine, J Immunol Res. 2019

This work demonstrates for the first time that a 48 mg sucralose sip increases serum insulin and unbalances monocyte subpopulations expressing CD11c and CD206 in noninsulin-resistant healthy young adults subjected to an OGTT. The apparently innocuous consumption of sucralose should be reexamined in light of these results...

Toxicity of Sucralose in Humans: A Review - HERE

March 2009 International Journal of Morphology 27(1)

... Various organs can be affected by ingestion of high doses of sucralose. As a result of the rise in global consumption of sweeteners and light- or diet-type products, studies are necessary to evaluate the action of this substance in the human species. ...

[...] However, it highlights the need to address individual responses to sucralose. [...]

Is Splenda, or Sucralose, Causally Linked to Inflammatory Bowel Disease? - HERE

Inflammatory Bowel Diseases, Volume 25, Issue 4, April 2019, Page e33

... Chassaing and Gewirtz comment that this study’s findings “suggest that consumption of this synthetic sweetener may be a specific factor that contributes to the development of IBD [inflammatory bowel disease] in persons genetically prone to this disorder.” ...

Assessment of exposure of Korean consumers to acesulfame K and sucralose using a stepwise approach - HERE

International Journal of Food Sciences and Nutrition Volume 64, 2013 - Issue 6

... Therefore, the sucralose concentration in sweetened beverages should be reduced; this would benefit the health of both high-level consumers and infants. ...

Energy Expenditure, Carbohydrate Oxidation and Appetitive Responses to Sucrose or Sucralose in Humans: A Pilot Study - HERE

National Library of Medicine, Nutrients. 2019 Aug; 11(8): 1782.

... This pilot study provides early findings that the replacement of sugars with NNS during food product formulation, with or without accompanying carbohydrate from maltodextrin, may have implications on human energy balance, especially human energy expenditure and carbohydrate oxidation patterns. Acutely, humans appear to compensate for energy shortfall from NNS but did not promote appetite or overeating beyond that. Findings from this pilot study should be verified and confirmed with bigger clinical trials in the future. ... (NNS - Non-nutritive sweetener)

Short-Term Consumption of Sucralose with, but Not without, Carbohydrate Impairs Neural and Metabolic Sensitivity to Sugar in Humans - HERE (pdf)

Dalenberg et al., 2020, Cell Metabolism 31, 493–502 March 3, 2020 ª 2020 Elsevier Inc

In Brief: Dalenberg et al. show that consuming the low-calorie sweetener sucralose with, but not without, a carbohydrate impairs insulin sensitivity in healthy humans. This effect is associated with a decreased brain response to sweet taste but no change in sweet taste perception. The results suggest that consumption of sucralose in the presence of a carbohydrate dysregulates gut-brain regulation of glucose metabolism

...These findings indicate that consumption of sucralose in the presence of a carbohydrate rapidly impairs glucose metabolism and results in longer-term decreases in brain, but not perceptual sensitivity to sweet taste, suggesting dysregulation of gut-brain control of glucose metabolism.

Effects of Sucralose Ingestion versus Sucralose Taste on Metabolic Responses to an Oral Glucose Tolerance Test in Participants with Normal Weight and Obesity: A Randomized Crossover Trial. HERE

Nutrients. 2019 Dec 20;12(1). pii: E29.

... Our data underscore a physiological role for taste perception in postprandial glucose responses, suggesting sweeteners should be consumed in moderation. ...

Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects - HERE

Environ. Sci. Technol. 2011, 45, 4, 1363-1369 - Publication Date:January 14, 2011

... In conclusion, we have not been able to demonstrate that sucralose given by intragastric infusion stimulates GLP-1 or GIP release in humans or elicits a feedback response to slow gastric emptying. This implies that artificial sweeteners may have no therapeutic benefit in the dietary management of diabetes, other than as a substitute for carbohydrate. ...

Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in patients with type 2 diabetes - HERE

European Journal of Clinical Nutrition volume 69, pages162–166 (2015)

Conclusions: Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in newly diagnosed type 2 diabetic patients.

Toxic emissions resulting from sucralose added to electronic cigarette liquids - HERE

Aerosol Science and Technology Volume 53, 2019 - Issue 10

... Heated sucralose-containing ECIG liquids produce two toxic compounds that can be found in the resulting aerosols. The two chloropropanols, 3-monochloro-1,2-propanediol (3-MCPD), and 1,3-dichloropropanol (1,3-DCP) that were detected under all conditions were found to be correlated significantly with liquid sucralose content. ...

Is sucralose too good to be true? - HERE

Biochemistry and Molecular Biology Education, 13th December 2011

... Student interest in artificial sweeteners can enhance the biochemistry classroom learning experience. This in class, guided‐inquiry activity focuses on sucralose and fits into a 50‐min biochemistry class for undergraduate science majors. ...

Interesting report, I thought that Sucralose was fully excreted by the body yet - (admin)

...Due to the water solubility of sucralose, some is absorbed by the body. A small portion of the absorbed sucralose is glucuronated and thus becomes more water soluble before being eliminated in the urine...

Impaired inactivation of digestive proteases by deconjugated bilirubin: The possible mechanism for inflammatory bowel disease -  HERE (Abstract)

Medical Hypotheses 59(2):159-63

... Sucralose was first approved for use in drinks and foods in Canada in 1991, which was in accordance with the dramatic increase of IBD seen in Alberta [111] and CD in Montreal [112] since early 1990s, as well as the finding in recent studies that Canada suddenly became a country with the highest incidence of IBD [113,114] . After Canada, sucralose was approved in Australia in 1993, in New Zealand in 1996, in the United States in 1998, and in the European Union in 2004, which was again in accordance with the dramatic increase or the record high incidence of IBD in Australia [115] , New Zealand [116] , the United States [117] and Norway [118] (Figure 4) [21] . Currently, sucralose has been approved for use in more than 80 counties [119] , and started to appear in rivers and other surface waters of many countries [120] . ...

Sucralose revisited: Rebuttal of two papers about Splenda safety - HERE

Regulatory Toxicology and Pharmacology, Volume 63, Issue 3, August 2012, Pages 505-508

Sucralose Affects Glycemic and Hormonal Responses to an Oral Glucose Load - HERE

CLINICAL CARE / EDUCATION / NUTRITION / PSYCHOSOCIAL RESEARCH| AUGUST 13 2013

... These data demonstrate that sucralose affects the glycemic and insulin responses to an oral 
glucose load in obese people who do not normally consume NNS. ...

Sucralose-Enhanced Degradation of Electronic Cigarette Liquids during Vaping. - HERE

Chem Res Toxicol. 2019 Jun 17;32(6):1241-1249.

... Quantities of sucralose as low as 0.05 mol % (0.24 wt %) in e-liquids lead to significant production of solvent degradation products. ...

The following reports are the effects on environmental bacteria, wastewater and environmental concerns:

Metabolic Effects of Sucralose on Environmental Bacteria - HERE

J Toxicol. 2013; 2013

... Sucralose is, however, increasing in its concentration due to its inability to be degraded by pH and temperature changes [4]. It is presently in wastewater effluents at levels of several μg/L (ppb). The Swedish Environmental Protection Agency warns that its breakdown is slow and the ecological impact is largely unknown; they emphasize that certain concentration levels may lead to damaging arthropod and cyanobacteria communities [15]...

Differential Bacteriostatic Effects of Sucralose on Various Species of Environmental Bacteria - HERE

International Scholarly Research Notices, Research Article | Open Access | Volume 2013 | Article ID 415070

[...] An unexpected contaminant in our aquatic and costal environments is artificial sweeteners [1]. Due to the human inability to metabolize them, they are passed on to the environment via human excrement. Naturally the highest concentration of artificial sweetener contaminants is in waste water treatment plants’ reservoirs. Artificial sweeteners such as saccharin and cyclamates are detected in lower concentrations and are found 90% degraded by the wastewater treatment process. Sucralose, however, is found in higher concentrations and is minimally degraded. [...]

Artificial Sweetener Sucralose in U.S. Drinking Water Systems - HERE

Environ. Sci. Technol. 2011, 45, 20, 8716–8722 Publication Date:August 31, 2011

The artificial sweetener sucralose has recently been shown to be a widespread of contaminant of wastewater, surface water, and groundwater. [...]

Quantification of four artificial sweeteners in Finnish surface waters with isotope-dilution mass spectrometry - HERE

Author links open overlay panel

Environmental Pollution | Volume 184, January 2014, Pages 391-396

...The artificial sweeteners sucralose (SCL), acesulfame (ACS), saccharin (SAC), and cyclamate (CYC) have been detected in environmental waters in Europe and North America.

Occurrence of the artificial sweetener sucralose in coastal and marine waters of the United States - HERE

Marine Chemistry Volume 116, Issues 1–4, 20 November 2009, Pages 13-17

... The first concentration data for the artificial sweetener sucralose (Splenda®) is presented for North American coastal and open ocean waters. [...]The data presented here suggest the persistence and widespread distribution of sucralose in natural aquatic matrices with subsequent incorporation into a major oceanographic current, the Gulf Stream, where global distribution may take place. ...

Analysis and occurrence of seven artificial sweeteners in German waste water and surface water and in soil aquifer treatment (SAT) HERE (Academia)

The widespread distribution of acesulfame, saccharin, cyclamate, and sucralose in the aquatic environment could be proven. Concentrations in two influents of German sewage treatment plants (STPs) were up to 190 μ g/L for cyclamate, about 40 μ g/L for acesulfame and saccharin, and less than 1 μ g/L for sucralose. Removal in the STPs was limited for acesulfame and sucralose and >94% for saccharin and cyclamate. The persistence of some artificial sweeteners during soil aquifer treatment was demonstrated and confirmed their environ-mental relevance. The use of sucralose and acesulfame astracers for anthropogenic contamination is conceivable. In German surface waters, acesulfame was the predominant artificial sweetener with concentrations exceeding 2 μ g/L. Other sweeteners were detected up to several hundred nanograms per liter in the order saccharin ≈ cyclamate >sucralose.

Sucralose screening in European surface waters using a solid-phase extraction-liquid chromatography–triple quadrupole mass spectrometry method - HERE

Journal of Chromatography A, Volume 1216, Issue 7, 13 February 2009, Pages 1126-1131

... An analytical method was developed for the analysis of sucralose, a persistent chlorinated calorie-free sugar substitute, in surface waters. ...

Development of a quantitative high-performance thin-layer chromatographic method for sucralose in sewage effluent, surface water, and drinking water - HERE

Journal of Chromatography A, Volume 1218, Issue 19, 13 May 2011, Pages 2745-2753

... Sucralose, a persistent chlorinated substance used as sweetener, can already be found in waste water, and various countries focused on the release of sucralose into the aquatic environment. ...

Fate of Sucralose through Environmental and Water Treatment Processes 

and Impact on Plant Indicator Species - HERE

Environ. Sci. Technol. 2011, 45, 4, 1363–1369 Publication Date:January 14, 2011

... Though sucralose does not appear toxic to plant growth, the peristent qualities of sucralose may lead to chronic low-dose exposure with largely unknown consequences for human and environmental health. ...