Drosophila melanogaster prefers compounds perceived sweet by humans

To understand the functional similarities of fly and mammalian taste receptors, we used a top-down approach that first established the fly sweetener-response profile. We employed the fruit fly Drosophila melanogaster, an omnivorous human commensal, and determined its sensitivity to an extended set of stimuli that humans find sweet. Flies were tested with all sweeteners in 2 assays that measured their taste reactivity (proboscis extension assay) and their ingestive preferences (free roaming ingestion choice test). A total of 21 sweeteners, comprised of 11 high-potency sweeteners, 2 amino acids, 5 sugars, 2 sugar alcohols, and a sweet salt (PbCl2), were tested in both assays. We found that wild-type Drosophila responded appetitively to most high-potency sweeteners preferred by humans, even those not considered sweet by rodents or new world monkeys. The similarities in taste preferences for sweeteners suggest that frugivorous/omnivorous apes and flies have evolved promiscuous carbohydrate taste detectors with similar affinities for myriad high-potency sweeteners. Whether these perceptual parallels are the result of convergent evolution of saccharide receptor-binding mechanisms remains to be determined.     

Artificial sweeteners stimulate horizontal transfer of extracellular antibiotic resistance genes through natural transformation

Antimicrobial resistance has emerged as a global threat to human health. Natural transformation is an important pathway for horizontal gene transfer, which facilitates the dissemination of antibiotic resistance genes (ARGs) among bacteria. Although it is suspected that artificial sweeteners could exert antimicrobial effects, little is known whether artificial sweeteners would also affect horizontal transfer of ARGs via transformation. Here we demonstrate that four commonly used artificial sweeteners (saccharin, sucralose, aspartame, and acesulfame potassium) promote transfer of ARGs via natural transformation in Acinetobacter baylyi ADP1, a model organism for studying competence and transformation. Such phenomenon was also found in a Gram-positive human pathogen Bacillus subtilis and mice faecal microbiome. We reveal that exposure to these sweeteners increases cell envelope permeability and results in an upregulation of genes encoding DNA uptake and translocation (Com) machinery. In addition, we find that artificial sweeteners induce an increase in plasmid persistence in transformants. We propose a mathematical model established to predict the long-term effects on transformation dynamics under exposure to these sweeteners. Collectively, our findings offer insights into natural transformation promoted by artificial sweeteners and highlight the need to evaluate these environmental contaminants for their antibiotic-like side effects.Subject terms: Antibiotics, Public health     

Modulation of T1R chemosensory receptors for sweet nutrients - new paradigms in metabolic regulation

Recent studies have demonstrated that the sweet-sensing receptors T1R2/3, thought to be "taste receptors" specifically expressed in lingual system, are also expressed and involved in the chemo-detection of sweetening molecules circulating in other organs. Researches that focus on their roles in intestinal absorption, metabolic regulation and glucose homeostasis, in particular, are increasing. Indeed, the sweet-sensing receptor could provide a new therapeutic target for certain metabolic disorders and diseases like obesity and diabetes. If the natural and artificial sweeteners agonists are diverse and well known, the "anti-sweeteners" antagonistic molecules are a class of compounds that received very little attention until now. Their potential roles and pharmacological relevance outside the taste system are discussed. Moreover, the recent finding that 2 major classes of compounds belonging respectively to the fields of medicine (fibrates) and agriculture (phenoxy-herbicides) are potent inhibitors of human T1R3 receptor is reported, raising new questions about their potential impact on human metabolism.     

The sweet taste quality is linked to a cluster of taste fibers in primates: lactisole diminishes preference and responses to sweet in S fibers (sweet best) chorda tympani fibers of M. fascicularis monkey

Background

Psychophysically, sweet and bitter have long been considered separate taste qualities, evident already to the newborn human. The identification of different receptors for sweet and bitter located on separate cells of the taste buds substantiated this separation. However, this finding leads to the next question: is bitter and sweet also kept separated in the next link from the taste buds, the fibers of the taste nerves? Previous studies in non-human primates, P. troglodytes, C. aethiops, M. mulatta, M. fascicularis and C. jacchus, suggest that the sweet and bitter taste qualities are linked to specific groups of fibers called S and Q fibers. In this study we apply a new sweet taste modifier, lactisole, commercially available as a suppressor of the sweetness of sugars on the human tongue, to test our hypothesis that sweet taste is conveyed in S fibers.

Results

We first ascertained that lactisole exerted similar suppression of sweetness in M. fascicularis, as reported in humans, by recording their preference of sweeteners and non- sweeteners with and without lactisole in two-bottle tests. The addition of lactisole significantly diminished the preference for all sweeteners but had no effect on the intake of non-sweet compounds or the intake of water. We then recorded the response to the same taste stimuli in 40 single chorda tympani nerve fibers. Comparison between single fiber nerve responses to stimuli with and without lactisole showed that lactisole only suppressed the responses to sweeteners in S fibers. It had no effect on the responses to any other stimuli in all other taste fibers.

Conclusion

In M. fascicularis, lactisole diminishes the attractiveness of compounds, which taste sweet to humans. This behavior is linked to activity of fibers in the S-cluster. Assuming that lactisole blocks the T1R3 monomer of the sweet taste receptor T1R2/R3, these results present further support for the hypothesis that S fibers convey taste from T1R2/R3 receptors, while the impulse activity in non-S fibers originates from other kinds of receptors. The absence of the effect of lactisole on the faint responses in some S fibers to other stimuli as well as the responses to sweet and non-sweet stimuli in non-S fibers suggest that these responses originate from other taste receptors.     

Taste receptor T1R3 is an essential molecule for the cellular recognition of the disaccharide trehalose

Recently, a sweet taste receptor family, the T1R family, that recognizes some carbohydrates including sucrose was identified. Although the T1R3 molecule is known to participate in heterodimers that are used as sweet- and umami-tasting receptors, there is no evidence that T1R3 alone recognizes similar ligands. We demonstrate for the first time that the candidate sweet taste receptor T1R3 is essential for the recognition and response to the disaccharide trehalose. Our system is a valuable tool not only for understanding the relationship between sweeteners and their receptors but also for exploring the diversities of their receptors, resulting in the design of new high-potency sweeteners.     

Sweet taste receptor agonists alter ovarian functions and ovarian cycles in aged mice

Saccharine sodium and rebaudioside A are low-calorie sweeteners, and the biologic effects of these sweeteners in rat ovaries are related to the activity of sweet taste receptors. Data on the impact and regulatory mechanisms underlying such sweeteners on the reproduction of aged animals are currently lacking. In the present study we assessed how the consumption of sweeteners affects the ovarian cycle, ovulation, biochemical indices, and other biologic functions. Thirty-six 1-year-old mice were randomly divided into 3 groups: a control (C) group receiving regular water, a saccharin sodium group receiving a 7.5 mM solution, and the rebaudioside A group receiving a 2.5 mM solution for 30 days. We observed no significant changes in body weights in any group. However, uterine weight in the rebaudioside A group significantly increased in diestrus, and we recorded a significant increase in the percentage of abnormal estrous cycles and the number of corpora lutea in the treatment groups. TUNEL staining and Immunoreactivity for the apoptosis-inducing factor (AIF) confirmed apoptosis in granulosa cells, oocyte, and corpus luteum. Serum glucose increased significantly in both treatment groups and there was a significant increase in cholesterol in the rebaudioside A group. Furthermore, the saccharin sodium-treated group exhibited elevated serum progesterone levels compared with the other groups. In conclusion, sweeteners manifested deleterious effects on reproductive indices in aged mice.     

Genetic signature of differential sensitivity to stevioside in the Italian population

The demand for diet products is continuously increasing, together with that for natural food ingredients. Stevioside and other steviol glycosides extracted from the leaves of the plant Stevia rebaudiana Bertoni are the first natural high-potency sweeteners to be approved for consumption in the United States and the European Union. However, the sweetness of these compounds is generally accompanied by aversive sensations, such as bitter and off-tastes, which may constitute a limit to their consumption. Moreover, consumers’ differences in sensitivity to high-potency sweeteners are well known, as well as difficulties in characterizing their aftertaste. Recently, TAS2R4 and TAS2R14 have been identified as the receptors that mediate the bitter off-taste of steviol glycosides in vitro. In the present study, we demonstrate that TAS2R4 gene polymorphism rs2234001 and TAS2R14 gene polymorphism rs3741843 are functional for stevioside bitterness perception.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-014-0401-y) contains supplementary material, which is available to authorized users.     

Whole nerve chorda tympani responses to sweeteners in C57BL/6ByJ and 129P3/J mice

The C57BL/6ByJ (B6) strain of mice exhibits higher preferences than does the 129P3/J (129) strain for a variety of sweet tasting compounds. We measured gustatory afferent responses of the whole chorda tympani nerve in these two strains using a broad array of sweeteners and other taste stimuli. Neural responses were greater in B6 than in 129 mice to the sugars sucrose and maltose, the polyol D-sorbitol and the non-caloric sweeteners Na saccharin, acesulfame-K, SC-45647 and sucralose. Lower neural response thresholds were also observed in the B6 strain for most of these stimuli. The strains did not differ in their neural responses to amino acids that are thought to taste sweet to mice, with the exception of L-proline, which evoked larger responses in the B6 strain. Aspartame and thaumatin, which taste sweet to humans but are not strongly preferred by B6 or 129 mice, did not evoke neural responses that exceeded threshold in either strain. The strains generally did not differ in their neural responses to NaCl, quinine and HCl. Thus, variation between the B6 and 129 strains in the peripheral gustatory system may contribute to differences in their consumption of many sweeteners.     

Interaction of sweet proteins with their receptor. A conformational study of peptides corresponding to loops of brazzein, monellin and thaumatin.

The mechanism of interaction of sweet proteins with the T1R2-T1R3 sweet taste receptor has not yet been elucidated. Low molecular mass sweeteners and sweet proteins interact with the same receptor, the human T1R2-T1R3 receptor. The presence on the surface of the proteins of "sweet fingers", i.e. protruding features with chemical groups similar to those of low molecular mass sweeteners that can probe the active site of the receptor, would be consistent with a single mechanism for the two classes of compounds. We have synthesized three cyclic peptides corresponding to the best potential "sweet fingers" of brazzein, monellin and thaumatin, the sweet proteins whose structures are well characterized. NMR data show that all three peptides have a clear tendency, in aqueous solution, to assume hairpin conformations consistent with the conformation of the same sequences in the parent proteins. The peptide corresponding to the only possible loop of brazzein, c[CFYDEKRNLQC(37-47)], exists in solution in a well ordered hairpin conformation very similar to that of the same sequence in the parent protein. However, none of the peptides has a sweet taste. This finding strongly suggests that sweet proteins recognize a binding site different from the one that binds small molecular mass sweeteners. The data of the present work support an alternative mechanism of interaction, the "wedge model", recently proposed for sweet proteins [Temussi, P. A. (2002) FEBS Lett.526, 1-3.].     

The history of sweet taste: not exactly a piece of cake

Understanding the molecular bases of sweet taste is of crucial importance not only in biotechnology but also for its medical implications, since an increasing number of people is affected by food-related diseases like, diabetes, hyperlipemia, caries, that are more or less directly linked to the secondary effects of sugar intake. Despite the interest paid to the field, it is only through the recent identification and functional expression of the receptor for sweet taste that new perspectives have been opened, drastically changing our approach to the development of new sweeteners. We shall give an overview of the field starting from the early days up to discussing the newest developments. After a review of early models of the active site, the mechanisms of interaction of small and macromolecular sweet molecules will be examined in the light of accurate modeling of the sweet taste receptor. The analysis of the homology models of all possible dimers allowed by combinations of the human T1R2 and T1R3 sequences of the sweet receptor and the closed (A) and open (B) conformations of the mGluR1 glutamate receptor shows that only 'type B' sites, either T1R2(B) and T1R3(B), can host the majority of small molecular weight sweeteners. Simultaneous binding to the A and B sites is not possible with two large sweeteners but is possible with a small molecule in site A and a large one in site B. This observation accounted for the first time for the peculiar phenomenon of synergy between some sweeteners. In addition to these two sites, the models showed an external binding site that can host sweet proteins.     

Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study

BackgroundThe food industry uses artificial sweeteners in a wide range of foods and beverages as alternatives to added sugars, for which deleterious effects on several chronic diseases are now well established. The safety of these food additives is debated, with conflicting findings regarding their role in the aetiology of various diseases. In particular, their carcinogenicity has been suggested by several experimental studies, but robust epidemiological evidence is lacking. Thus, our objective was to investigate the associations between artificial sweetener intakes (total from all dietary sources, and most frequently consumed ones: aspartame [E951], acesulfame-K [E950], and sucralose [E955]) and cancer risk (overall and by site).Methods and findingsOverall, 102,865 adults from the French population-based cohort NutriNet-Santé (2009–2021) were included (median follow-up time = 7.8 years). Dietary intakes and consumption of sweeteners were obtained by repeated 24-hour dietary records including brand names of industrial products. Associations between sweeteners and cancer incidence were assessed by Cox proportional hazards models, adjusted for age, sex, education, physical activity, smoking, body mass index, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, and baseline intakes of energy, alcohol, sodium, saturated fatty acids, fibre, sugar, fruit and vegetables, whole-grain foods, and dairy products. Compared to non-consumers, higher consumers of total artificial sweeteners (i.e., above the median exposure in consumers) had higher risk of overall cancer (n = 3,358 cases, hazard ratio [HR] = 1.13 [95% CI 1.03 to 1.25], P-trend = 0.002). In particular, aspartame (HR = 1.15 [95% CI 1.03 to 1.28], P = 0.002) and acesulfame-K (HR = 1.13 [95% CI 1.01 to 1.26], P = 0.007) were associated with increased cancer risk. Higher risks were also observed for breast cancer (n = 979 cases, HR = 1.22 [95% CI 1.01 to 1.48], P = 0.036, for aspartame) and obesity-related cancers (n = 2,023 cases, HR = 1.13 [95% CI 1.00 to 1.28], P = 0.036, for total artificial sweeteners, and HR = 1.15 [95% CI 1.01 to 1.32], P = 0.026, for aspartame). Limitations of this study include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.ConclusionsIn this large cohort study, artificial sweeteners (especially aspartame and acesulfame-K), which are used in many food and beverage brands worldwide, were associated with increased cancer risk. These findings provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03335644","term_id":"NCT03335644"}}NCT03335644.

Charlotte Debras and colleagues investigate investigate associations between artificial sweetener intakes and cancer risk in adults from a French population-based cohort.     

POINT: Artificial Sweeteners and Obesity—Not the Solution and Potentially a Problem

ObjectiveNonnutritive sweeteners (NNS) have been widely implemented as replacements for naturally occurring sugars in a wide array of foods, beverages, and non-consumables for the sake of reducing calories. The use of these products, whether naturally occurring or manufactured, have become commonplace and accepted as de facto beneficial. This point argues that rigorous analysis of the available data do not confirm benefit and indeed suggest harm.MethodsA literature review was conducted on all the available NNS supplements that are commonly used in all types of products. There was a focus on studies that evaluated the long-term as well as neurohormonal effects of NNS products. Key words used in the search included artificial sweeteners, nonnutritive sweeteners, saccharin, aspartame, acesulfame, sucralose, stevia, xylitol, and erythritol.ResultsThere was a consistent trend of no to minimal benefit when NNS were used instead of calorie-containing sweeteners particularly in persons with obesity or pre-diabetes risks. There was a consistent finding of detriment to the neurohormonal regulation of satiety, weight, and energy regulation. The only studies that were neutral to positive were biased studies funded by the large food and beverage corporations or done in healthy weight individuals without any underlying health concerns and for a very short time frame.ConclusionAlthough NNS usage has become ubiquitous, there has been very little in the way of rigorous review of the neurohormonal and physiologic effects. The arguments for NNS are purely thermodynamic in nature despite the overwhelming evidence that obesity and adiposity-related diseases are not that simplistic in their pathophysiology. Given that there are differences in how individuals process nutrition signals, very few studies focus on gender or disease predisposition differences and how they affect the outcomes when NNS are used. Studies that controlled these variables showed worsening outcomes when NNS products are used in the fight against adiposity-related diseases, such as hypertension, dyslipidemia, and diabetes. Alterations in the gut microbiome towards a more inflammatory pattern of gut microbiota is a disturbing finding in acute as well as chronic users of NNS regardless of baseline weight or disease. Most importantly, there were numerous studies that found long-term damage to the neurohormonal control of satiety in chronic users of NNS. In the fight against obesity and adiposity-related diseases, we cannot afford to blindly accept their usage based on a broken paradigm of thermodynamics and false assumptions that we are all created equal biologically.     

Artificial Sweeteners in a Large Canadian River Reflect Human Consumption in the Watershed

Artificial sweeteners have been widely incorporated in human food products for aid in weight loss regimes, dental health protection and dietary control of diabetes. Some of these widely used compounds can pass non-degraded through wastewater treatment systems and are subsequently discharged to groundwater and surface waters. Measurements of artificial sweeteners in rivers used for drinking water production are scarce. In order to determine the riverine concentrations of artificial sweeteners and their usefulness as a tracer of wastewater at the scale of an entire watershed, we analyzed samples from 23 sites along the entire length of the Grand River, a large river in Southern Ontario, Canada, that is impacted by agricultural activities and urban centres. Municipal water from household taps was also sampled from several cities within the Grand River Watershed. Cyclamate, saccharin, sucralose, and acesulfame were found in elevated concentrations despite high rates of biological activity, large daily cycles in dissolved oxygen and shallow river depth. The maximum concentrations that we measured for sucralose (21 µg/L), cyclamate (0.88 µg/L), and saccharin (7.2 µg/L) are the highest reported concentrations of these compounds in surface waters to date anywhere in the world. Acesulfame persists at concentrations that are up to several orders of magnitude above the detection limit over a distance of 300 km and it behaves conservatively in the river, recording the wastewater contribution from the cumulative population in the basin. Acesulfame is a reliable wastewater effluent tracer in rivers. Furthermore, it can be used to assess rates of nutrient assimilation, track wastewater plume dilution, separate human and animal waste contributions and determine the relative persistence of emerging contaminants in impacted watersheds where multiple sources confound the usefulness of other tracers. The effects of artificial sweeteners on aquatic biota in rivers and in the downstream Great Lakes are largely unknown.     

A REAPPRAISAL OF THE USE OF MULTIDIMENSIONAL SCALING TO INVESTIGATE THE SENSORY CHARACTERISTICS OF SWEETENERS

Previous investigations of the sensory characteristics of sweeteners using a multidimensional scaling (MDS) approach, have involved sweeteners which were not matched for sweetness. Under such circumstances, part of the estimated distance between sweeteners is attributable to sweetness differences. This detracts from the value of the consequent MDS space, when the main objective is usually to investigate sensory characteristics other than sweetness. In this study, the MDS approach was applied to sweetener solutions which were matched for sweetness with 5% sucrose. The direction of any residual sweetness differences was identified by including 1,3,5 and 7% sucrose solutions, all matched to equal viscosity, in the study. From the resulting three dimensional MDS sweetener space, it was evident that Dimension 1 was almost exclusively due to sweetness differences whereas Dimensions 2 and 3 were devoid of influence from sweetness and hence represent the sweeteners with respect to their other sensory characteristics.     

Quantitative and qualitative evaluation of high-intensity sweeteners and sweetener mixtures

High intensity sweeteners were evaluated for sweetness and bitternessintensity using time-intensity scaling. Mean intensities of50:50 mixtures as well as the single sweeteners were used tocompute predicted scores which were compared to the observedscores as a means of evaluating additivity in the mixtures.Concentration-dependent effects of subadditivity, additivityand hyperadditivity were observed within some sweetener pairs,but these did not follow any consistent pattern across sweeteners.Synergy, a special case of hyperadditivity evaluated by comparingpredicted to observed scores, was seen in mixtures of aspartameand acesulfame-K at all concentrations. Aspartame/saccharinblends were synergistic only at the lowest concentration tested,despite the structural similarity between acesulfame-K and saccharin.Blends of sucrose/aspartame and acesulfame-K/saccharin did notexhibit synergy. Comparisons based on ratings of initial sweetnessrather than the whole time-intensity curve, reflected previousfindings of synergy in some sweetener pairs.     

Sweetener preference of C57BL/6ByJ and 129P3/J mice

Previous studies have shown large differences in taste responses to several sweeteners between mice of the C57BL/6ByJ (B6) and 129P3/J (129) inbred strains. The goal of this study was to compare behavioral responses of B6 and 129 mice to a wider variety of sweeteners. Seventeen sweeteners were tested using two-bottle preference tests with water. Three main patterns of strain differences were evident. First, sucrose, maltose, saccharin, acesulfame-K, sucralose and SC-45647 were preferred by both strains, but the B6 mice had lower preference thresholds and higher solution intakes. Second, the amino acids D-phenylalanine, D-tryptophan, L-proline and glycine were highly preferred by B6 mice, but not by 129 mice. Third, glycyrrhizic acid, neohesperidin dihydrochalcone, thaumatin and cyclamate did not evoke strong preferences in either strain. Aspartame was neutral to all 129 and some B6 mice, but other B6 mice strongly preferred it. Thus, compared with the 129 mice the B6 mice had higher preferences for sugars, sweet tasting amino acids and several but not all non-caloric sweeteners. Glycyrrhizic acid, neohesperidin, thaumatin and cyclamate are not palatable to B6 or 129 mice.     

Nonnutritive sweeteners can promote the dissemination of antibiotic resistance through conjugative gene transfer

Antimicrobial resistance (AMR) poses a worldwide threat to human health and biosecurity. The spread of antibiotic resistance genes (ARGs) via conjugative plasmid transfer is a major contributor to the evolution of this resistance. Although permitted as safe food additives, compounds such as saccharine, sucralose, aspartame, and acesulfame potassium that are commonly used as nonnutritive sweeteners have recently been associated with shifts in the gut microbiota similar to those caused by antibiotics. As antibiotics can promote the spread of antibiotic resistance genes (ARGs), we hypothesize that these nonnutritive sweeteners could have a similar effect. Here, we demonstrate for the first time that saccharine, sucralose, aspartame, and acesulfame potassium could promote plasmid-mediated conjugative transfer in three established conjugation models between the same and different phylogenetic strains. The real-time dynamic conjugation process was visualized at the single-cell level. Bacteria exposed to the tested compounds exhibited increased reactive oxygen species (ROS) production, the SOS response, and gene transfer. In addition, cell membrane permeability increased in both parental bacteria under exposure to the tested compounds. The expression of genes involved in ROS detoxification, the SOS response, and cell membrane permeability was significantly upregulated under sweetener treatment. In conclusion, exposure to nonnutritive sweeteners enhances conjugation in bacteria. Our findings provide insight into AMR spread and indicate the potential risk associated with the presence of nonnutritive sweeteners.Subject terms: Microbial ecology, Water microbiology     

Artificial sweeteners and salts producing a metallic taste sensation activate TRPV1 receptors

Throughout the world many people use artificial sweeteners (AS) for the purpose of reducing caloric intake. The most prominently used of these molecules include saccharin, aspartame (Nutrasweet), acesulfame-K, and cyclamate. Despite the caloric advantage they provide, one key concern in their use is their aversive aftertaste that has been characterized on a sensory level as bitter and/or metallic. Recently, it has been shown that the activation of particular T2R bitter taste receptors is partially involved with the bitter aftertaste sensation of saccharin and acesulfame-K. To more fully understand the biology behind these phenomena we have addressed the question of whether AS could stimulate transient receptor potential vanilloid-1 (TRPV1) receptors, as these receptors are activated by a large range of structurally different chemicals. Moreover, TRPV1 receptors and/or their variants are found in taste receptor cells and in nerve terminals throughout the oral cavity. Hence, TRPV1 activation could be involved in the AS aftertaste or even contribute to the poorly understood metallic taste sensation. Using Ca(2+) imaging on TRPV1 receptors heterologously expressed in the human embryonic kidney (HEK) 293 cells and on dissociated primary sensory neurons, we find that in both systems, AS activate TRPV1 receptors, and, moreover, they sensitize these channels to acid and heat. We also found that TRPV1 receptors are activated by CuSO(4), ZnSO(4), and FeSO(4), three salts known to produce a metallic taste sensation. In summary, our results identify a novel group of compounds that activate TRPV1 and, consequently, provide a molecular mechanism that may account for off tastes of sweeteners and metallic tasting salts.     

Bladder cancer: smoking,beverages and artificial sweeteners

A matched patient-control study of bladder cancer examined the relationship of the disease to occupation, smoking and intake of tea, coffee, cola, alcohol and artificial sweeteners.There was no association of disease with occupation for these patients. Heavy smoking gave relative risks of 6.37 and 4.36 for men and women respectively; there was evidence of a dose-response relationship. Tea and coffee intake did not increase the risk of disease nor did prolonged use of artificial sweeteners. Alcohol and cola intake increased the relative risk of bladder cancer among male smokers. There is some suggestion that smoking interacts with both alcohol and cola intake in the production of bladder cancer.     

Rapid entry of bitter and sweet tastants into liposomes and taste cells: implications for signal transduction

Someamphipathic bitter tastants and non-sugar sweeteners are directactivators of G proteins and stimulate transduction pathways in cellsnot related to taste. We demonstrate that the amphipathic bittertastants quinine and cyclo(Leu-Trp) and the non-sugar sweetener saccharin translocate rapidly through multilamellar liposomes. Furthermore, when rat circumvallate (CV) taste buds were incubated withthe above tastants for 30 s, their intracellular concentrations increased by 3.5- to 7-fold relative to their extracellularconcentrations. The time course of this dramatic accumulation was alsomonitored in situ in rat single CV taste buds under a confocallaser-scanning microscope. Tastants were clearly localized to the tastecell cytosol. It is proposed that, due to their rapid permeation into taste cells, these amphipathic tastants may be available for activation of signal transduction components (e.g., G proteins) directly withinthe time course of taste sensation. Such activation may occur inaddition to the action of these tastants on putative G protein-coupledreceptors. This phenomenon may be related to the slow taste onset andlingering aftertaste typically produced by many bitter tastants andnon-sugar sweeteners.