Artificial Sweeteners Induce Glucose Intolerance by Altering... : Obstetrical & Gynecological Survey

Noncaloric artificial sweeteners (NASs) are popular because of their low caloric intake and perceived health benefits for weight loss and normalization of blood sugar levels. Artificial sweeteners have been increasingly introduced as an additive into common foods as an alternative to high-caloric sugars. However, increased consumption has coincided with a dramatic increase worldwide in obesity and diabetes epidemics. Scientific data supporting the safety and benefits of NAS consumption are sparse and controversial.

Most NASs are not digested in the gastrointestinal tract and directly encounter the intestinal microbiota. The diet modulates microbiota composition and function in the healthy/lean state as well as in obesity and diabetes mellitus. Intestinal dysbiosis has been associated with propensity to metabolic syndrome.

The investigators studied NAS-mediated changes of microbiota composition and function of mice to determine whether chronic NAS consumption exacerbates glucose intolerance in mice. Formulations of saccharin, sucralose, or aspartame were added to the drinking water of mice. The data provide conclusive proof that NAS-mediated intestinal dysbiosis is directly responsible for the development of glucose intolerance in mice. Treating mice with antibiotics eradicated many intestinal bacteria and fully reversed artificial sweeteners' effects on glucose metabolism. Transfer of fecal microbiota from mice that consumed artificial sweeteners to “germ-free” mice resulted in a complete transmission of the glucose intolerance into the recipient mice. Incubating the microbiota anerobically with artificial sweeteners also induced glucose intolerance in the sterile mice. Profound changes in the population of intestinal bacteria have been linked to host susceptibility to obesity, diabetes, and other metabolic diseases in both mice and humans. Similar NAS-induced dysbiosis and glucose intolerance were demonstrated in healthy human subjects.

These findings show that NAS consumption in both mice and humans increases the risk of glucose intolerance through adverse metabolic effects mediated by intestinal dysbiosis. The data suggest that the widespread use of NAS should be reassessed.

Popular artificial sweetener, Sucralose, not so sweet

The study involved an experiment using Sprague-Dawley rats that were
administered the artificial sweetener over a 12-week period. Following a
bacterial analysis of the rats' fecal samples and measurement of fecal
pH, the article concluded that artificial sweetener resulted in various
adverse effects in the rats, including:

• Reduction in beneficial fecal microflora
• Increased fecal pH
• Enhanced expression levels of P-gp, CYP3A4,and CYP2D1, which are known to limit the bioavailability of orally administered drugs

"At concentrations typically used in foods and drinks, sucralose suppresses beneficial bacteria
in the gastrointestinal tract with less effect on pathogenic bacteria,"
article co-author Susan Schiffman, Ph.D said. "Most consumers are
unaware of these effects because no warning label appears on products
containing sucralose." Schiffman also said went onto saythat the change
in balance of gastrointestinal bacteria has been associated with weight
gain and obesity. At elevated levels, sucralose also damages DNA.
These biological effects occur at the levels of sucralose currently
approved by regulatory agencies for use in the food supply.

Related articles

• Biological effects of the popular artificial sweetener sucralose (medicalnewstoday.com)

Biological effects of the popular artificial sweetener sucralose - Medical News Today

Some of the biological effects of sucralose described by Schiffman and Rother include:
alterations in insulin, blood glucose, and glucagon-like peptide 1 (GLP-1) levels,

• metabolism of sucralose in the gastrointestinal tract to metabolites whose identity and safety profile are unknown,
• induction of cyctochrome P450 and P-glycoprotein in the gastrointestinal
  tract to levels that may limit the bioavailability of therapeutic
  drugs,
• reduction in the number and balance of beneficial bacteria in the gastrointestinal tract,
• histopathological findings in gastrointestinal tract including
  lymphocytic infiltrates into epithelium, epithelial scarring, mild
  depletion of goblet cells and glandular disorganization in the colon,
• decomposition and generation of chloropropanols (a potentially toxic
  class of compounds) during baking, and mutagenic alterations using
  several types of biological assays

Sucralose, A Synthetic Organochlorine Sweetener: Overview Of Biological Issues - Journal of Toxicology and Environmental Health

Sucralose is a synthetic organochlorine sweetener (OC) that is a common ingredient in the world's food supply. Sucralose interacts with chemosensors in the alimentary tract that play a role in sweet taste sensation and hormone secretion. In rats, sucralose ingestion was shown to increase the expression of the efflux transporter P-glycoprotein (P-gp) and two cytochrome P-450 (CYP) isozymes in the intestine. P-gp and CYP are key components of the presystemic detoxification system involved in first-pass drug metabolism. The effect of sucralose on first-pass drug metabolism in humans, however, has not yet been determined. In rats, sucralose alters the microbial composition in the gastrointestinal tract (GIT), with relatively greater reduction in beneficial bacteria. Although early studies asserted that sucralose passes through the GIT unchanged, subsequent analysis suggested that some of the ingested sweetener is metabolized in the GIT, as indicated by multiple peaks found in thin-layer radiochromatographic profiles of methanolic fecal extracts after oral sucralose administration. The identity and safety profile of these putative sucralose metabolites are not known at this time. Sucralose and one of its hydrolysis products were found to be mutagenic at elevated concentrations in several testing methods. 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.

Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements

The negative impact of consuming sugar-sweetened beverages on weight and other health outcomes has been increasingly recognized; therefore, many people have turned to high-intensity sweeteners like aspartame, sucralose, and saccharin as a way to reduce the risk of these consequences. However, accumulating evidence suggests that frequent consumers of these sugar substitutes may also be at increased risk of excessive weight gain, metabolic syndrome, type 2 diabetes, and cardiovascular disease. This paper discusses these findings and considers the hypothesis that consuming sweet-tasting but noncaloric or reduced-calorie food and beverages interferes with learned responses that normally contribute to glucose and energy homeostasis. Because of this interference, frequent consumption of high-intensity sweeteners may have the counterintuitive effect of inducing metabolic derangements.

Sucralose Affects Glycemic and Hormonal Responses to an Oral Glucose Load

Nonnutritive sweeteners (NNS), such as sucralose, have been reported to have metabolic effects in animal models. However, the relevance of these findings to human subjects is not clear. We evaluated the acute effects of sucralose ingestion on the metabolic response to an oral glucose load in obese subjects.

RESEARCH DESIGN AND METHODS Seventeen obese subjects (BMI 42.3 ± 1.6 kg/m2) who did not use NNS and were insulin sensitive (based on a homeostasis model assessment of insulin resistance score ≤2.6) underwent a 5-h modified oral glucose tolerance test on two separate occasions preceded by consuming either sucralose (experimental condition) or water (control condition) 10 min before the glucose load in a randomized crossover design. Indices of β-cell function, insulin sensitivity (S_I), and insulin clearance rates were estimated by using minimal models of glucose, insulin, and C-peptide kinetics.

RESULTS Compared with the control condition, sucralose ingestion caused 1) a greater incremental increase in peak plasma glucose concentrations (4.2 ± 0.2 vs. 4.8 ± 0.3 mmol/L; P = 0.03), 2) a 20 ± 8% greater incremental increase in insulin area under the curve (AUC) (P < 0.03), 3) a 22 ± 7% greater peak insulin secretion rate (P < 0.02), 4) a 7 ± 4% decrease in insulin clearance (P = 0.04), and 5) a 23 ± 20% decrease in S_I (P = 0.01). There were no significant differences between conditions in active glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, glucagon incremental AUC, or indices of the sensitivity of the β-cell response to glucose.

CONCLUSIONS 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.

Splenda Causes Cancer Concern

Following the discovery in a new study that mice have a higher risk of developing cancer after eating the popular British-made low-calorie artificial sweetener sucralose (Splenda), a leading cancer scientist calls for urgent research