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Concept: Sweeteners

29

Regulatory authorities worldwide have found the nonnutritive sweetener, sucralose, to be noncarcinogenic, based on a range of studies. A review of these and other studies found through a comprehensive search of electronic databases, using appropriate key terms, was conducted and results of that review are reported here. An overview of the types of studies relied upon by regulatory agencies to assess carcinogenicity potential is also provided as context. Physiochemical and pharmacokinetic/toxicokinetic studies confirm stability under conditions of use and reveal no metabolites of carcinogenic potential. In vitro and in vivo assays reveal no confirmed genotoxic activity. Long-term carcinogenicity studies in animal models provide no evidence of carcinogenic potential for sucralose. In studies in healthy adults, sucralose was well-tolerated and without evidence of toxicity or other changes that might suggest a potential for carcinogenic effects. In summary, sucralose does not demonstrate carcinogenic activity even when exposure levels are several orders of magnitude greater than the range of anticipated daily ingestion levels.

Concepts: Oncology, Energy, In vivo, Toxicology, In vitro, Carcinogen, Mutagen, Sweeteners

28

Compared to simple sugars, complex carbohydrates have been assumed invisible to taste. However, two recent studies proposed that there may be a perceivable taste quality elicited by complex carbohydrates independent of sweet taste. There is precedent with behavioural studies demonstrating that rats are very attracted to complex carbohydrates, and that complex carbohydrates are preferred to simple sugars at low concentrations. This suggests that rats may have independent taste sensors for simple sugars and complex carbohydrates. The aim of this paper is to investigate oral sensitivities of two different classes of complex carbohydrates (a soluble digestible and a soluble non-digestible complex carbohydrate), and to compare these to other caloric and non-nutritive sweeteners in addition to the prototypical tastes using two commonly used psychophysical measures. There were strong correlations between the detection thresholds and mean intensity ratings for complex carbohydrates (maltodextrin, oligofructose) (r = 0.94, P < 0.001). There were no significant correlations between the detection thresholds of the complex carbohydrates (maltodextrin, oligofructose) and the sweeteners (glucose, fructose, sucralose, Rebaudioside A, erythritol) (all P > 0.05). However, moderate correlations were observed between perceived intensities of complex carbohydrates and sweeteners (r = 0.48-0.61, P < 0.05). These data provide evidence that complex carbohydrates can be sensed in the oral cavity over a range of concentrations independent of sweet taste sensitivity at low concentrations, but with partial overlap with sweet taste intensity at higher concentrations.

Concepts: Glucose, Carbohydrate, Sugar, Disaccharide, Monosaccharide, Sucrose, Sweeteners, Sugar substitute

27

Artificial sweeteners are gaining acceptance as tracers of human wastewater in the environment. The 3 artificial sweeteners analyzed in this study were detected in leachate or leachate-impacted groundwater at levels comparable to those of untreated wastewater at 14 of 15 municipal landfill sites tested, including several closed for >50 years. Saccharin was the dominant sweetener in old (pre-1990) landfills, while newer landfills were dominated by saccharin and acesulfame (introduced 2 decades ago; dominant in wastewater). Cyclamate was also detected, but less frequently. A case study at one site illustrates the use of artificial sweeteners to identify a landfill-impacted groundwater plume discharging to a stream. The study results suggest that artificial sweeteners can be useful tracers for current and legacy landfill contamination, with relative abundances of the sweeteners potentially providing diagnostic ability to distinguish different landfills or landfill cells, including crude age-dating, and to distinguish landfill and wastewater sources.

Concepts: Groundwater, Anaerobic digestion, Leachate, Landfill, Land reclamation, Aspartame, Sweeteners, Sucralose

27

The determination of honey authenticity is of importance to ensure its quality and safety. There is an urgent need of effective methods to detect adulterated honey. A simple, rapid, and effective HPLC-DAD method was developed to detect honey adulteration by rice syrup, using a characteristic compound from rice syrup, which is presently difficult to detect by current analytical methods. The characteristic compound was identified as 2-acetylfuran-3-glucopyranoside (AFGP) by MS and NMR. Based on HPLC analyses, the average concentration of AFGP was 92 ± 60 mg/kg in rice syrup. However, AFGP was not detected in any of the natural honey samples, so it could be used as a maker for the detection of honey adulteration by rice syrup. The developed HPLC-DAD method enabled a rapid detection of honey samples adulterated with 10% rice syrup. Using the developed method, 16 out of 186 honey samples from different markets were found to be adulterated with rice syrup.

Concepts: Honey, Rice, Market, Sweeteners, Adulterant, Syrup, Brown rice syrup

26

G protein-coupled receptors mediate responses to a myriad of ligands, some of which regulate adipocyte differentiation and metabolism. The sweet taste receptors T1R2 and T1R3 are G protein-coupled receptors that function as carbohydrate sensors in taste buds, gut and pancreas. Here we report that sweet taste receptors T1R2 and T1R3 are expressed throughout adipogenesis and in adipose tissues. Treatment of mouse and human precursor cells with artificial sweeteners, saccharin and acesulfame K, enhances adipogenesis. Saccharin treatment of 3T3-L1 cells and primary mesenchymal stem cells rapidly stimulates phosphorylation of Akt and downstream targets with functions in adipogenesis such as CREB and FOXO1; however, increased expression of PPARγ and C/EBPα is not observed until relatively late in differentiation. Saccharin-stimulated Akt phosphorylation at T308 occurs within 5 mins, is phosphatidylinositol 3-kinase-dependent, and occurs in the presence of high concentrations of insulin and dexamethasone; phosphorylation of S473 occurs more gradually. Surprisingly, neither saccharin-stimulated adipogenesis nor T308 phosphorylation is dependent on expression of T1R2 and/or T1R3, although S473 phosphorylation is impaired in T1R2/T1R3 double knockout precursors. In mature adipocytes, artificial sweetener treatment suppresses lipolysis even in presence of forskolin, and lipolytic responses are correlated with phosphorylation of hormone sensitive lipase. Suppression of lipolysis by saccharin in adipocytes is also independent of T1R2 and T1R3. These results suggest that some artificial sweeteners have previously uncharacterized metabolic effects on adipocyte differentiation and metabolism, and that effects of artificial sweeteners on adipose tissue biology may be largely independent of the classical sweet taste receptors, T1R2 and T1R3.

Concepts: Signal transduction, Mesenchymal stem cell, Fat, Adipose tissue, Adipocyte, Sugar, Sweeteners, Sucralose

25

Neurobiological and genetic mechanisms underlying increased intake of and preference for nutritive sugars over non-nutritive sweeteners are not fully understood. We examined the roles of subnuclei of the amygdala in the shift in preference for a nutritive sugar. Food-deprived mice alternately received caloric sucrose (1.0 M) on odd-numbered training days and a non-caloric artificial sweetener (2.5 mM saccharin) on even-numbered training days. During training, mice with sham lesions of the basolateral (BLA) or central (CeA) nucleus of the amygdala increased their intake of 1.0 M sucrose, but not saccharin. Trained mice with sham lesions showed a significant shift in preference toward less concentrated sucrose (0.075 M) over the saccharin in a two-bottle choice test, although the mice showed an equivalent preference for these sweeteners before training. No increased intake of or preference for sucrose before and after the alternating training was observed in non-food-deprived mice. Excitotoxic lesions centered in the BLA impaired the increase in 1.0 M sucrose intake and shift in preference toward 0.075 M sucrose over saccharin. Microlesions with iontophoretic excitotoxin injections into the CeA did not block the training-dependent changes. These results suggest that food-deprived animals selectively shift their preference for a caloric sugar over a non-caloric sweetener through the alternate consumption of caloric and non-caloric sweet substances. The present data also suggest that the BLA, but not CeA, plays a role in the selective shift in sweetener preference. (232 words).

Concepts: Glucose, Carbohydrate, Sugar, Honey, Sweeteners, Stevia, Sugar substitute, Sucralose

24

The American public is increasingly concerned about risks associated with food additives like high-fructose corn syrup (HFCS). To promote its product as safe, the Corn Refiners Association (CRA) employed two forms of straw-person arguments. First, the CRA opportunistically misrepresented HFCS opposition as inept. Second, the CRA strategically chose to refute claims that were easier to defeat while remaining ambiguous about more complex points of contention. We argue that CRA’s discursive contributions represented unreasonable yet sustainable use of straw-person arguments in debates surrounding health and risk.

Concepts: Starch, Food additive, Argumentation theory, High-fructose corn syrup, Corn syrup, Sweeteners, Fallacy, Syrup

22

Public health recommendations call for a reduction in added sugars; however, controversy exits over whether all nutritive sweeteners produce similar metabolic effects.

Concepts: Nutrition, Carbohydrate, Sugar, Honey, Fructose, Sucrose, Corn syrup, Sweeteners

20

It has been postulated that fructose-induced triglyceride synthesis is augmented when accompanied by glucose. Chronic elevations could lead to excess fat accumulation in the liver and ectopic fat deposition in muscles, which in turn could contribute to the induction of abnormalities in glucose homeostasis, insulin resistance, and the subsequent development of type 2 diabetes. Our objective was to evaluate the effect of the addition of commonly consumed fructose- and (or) glucose-containing sugars in the usual diet on liver fat content and intramuscular adipose tissue. For 10 weeks, 64 individuals (mean age, 42.16 ± 11.66 years) consumed low-fat milk sweetened with either high-fructose corn syrup (HFCS) or sucrose; the added sugar matched consumption levels of fructose in the 25th, 50th, and 90th percentiles of the population. The fat content of the liver was measured with unenhanced computed tomography imaging, and the fat content of muscle was assessed with magnetic resonance imaging. When the 6 HFCS and sucrose groups were averaged, there was no change over the course of 10 weeks in the fat content of the liver (13.32% ± 10.49% vs. 13.21% ± 10.75%; p > 0.05), vastus lateralis muscle (3.07 ± 0.74 g per 100 mL vs. 3.15 ± 0.84 g per 100 mL; p > 0.05), or gluteus maximus muscle (4.08 ± 1.50 g per 100 mL vs. 4.24 ± 1.42 g per 100 mL; p > 0.05). Group assignment did not affect the result (interaction > 0.05). These data suggest that when fructose is consumed as part of a typical diet in normally consumed sweeteners, such as sucrose or HFCS, ectopic fat storage in the liver or muscles is not promoted.

Concepts: Glucose, Obesity, Muscle, Adipose tissue, Sugar, Fructose, Sucrose, Sweeteners

16

Previous work showed the non-nutritive polyol sweetener Erythritol was toxic when ingested by Drosophila melanogaster (Meigen, 1930). This study assessed whether insect toxicity is a general property of polyols. Among tested compounds, toxicity was highest for erythritol. Adult fruit flies (D. melanogaster) fed erythritol had reduced longevity relative to controls. Other polyols did not reduce longevity; the only exception was a weaker but significant reduction of female (but not male) longevity when flies were fed D-mannitol. We conclude at least some non-nutritive polyols are not toxic to adult D. melanogaster when ingested for 17 days. The longer time course (relative to erythritol) and female specificity of D-mannitol mortality suggests different mechanisms for D-mannitol and erythritol toxicity to D. melanogaster.

Concepts: Insect, Drosophila melanogaster, Drosophila, Flies, Drosophilidae, Sweeteners, Xylitol, Sugar alcohol