Artificial sweetener saccharin disrupts intestinal epithelial cells' barrier function in vitro.

SCOPE: Consumption of non-nutritive sweeteners (NNS) is a dietary practice used by those who wish to lose weight or by patients on a sugar-restricted diet such as those with DM2. Although these substances are safe, possible biological interactions with the digestive tract, particularly in relation to intestinal permeability, have not been studied. Thus, the current work sought to investigate the action of different NNS on intestinal permeability using an in vitro Caco-2 cell model. METHODS AND RESULTS: Caco-2 cells were incubated with acesulfame K, aspartame, saccharin, or sucralose at equimolar concentrations. Acesulfame K, aspartame, and sucralose did not disrupt monolayer integrity in the cells. However, saccharin increased paracellular permeability and decreased transepithelial electrical resistance (TEER) via a non-cytotoxic mechanism. The levels of the tight junction protein claudin-1 were reduced in Caco-2 cells that had previously been exposed to saccharin. The inhibition of nuclear factor-κB (NF-κB) was able to prevent the reduction in TEER induced by saccharin treatment. Thalidomide, as an inhibitor of ubiquitin ligase, was able to prevent the decrease in claudin-1 protein expression and the TEER reduction in Caco-2 cells. CONCLUSIONS: Saccharin disrupts monolayer integrity and alters paracellular permeability in a Caco-2 cell monolayer model, via a mechanism involving NF-κB activation, resulting in the ubiquitination of the tight junction protein claudin-1. Saccharin consumption may potentially alter the intestinal integrity in humans.

Noncaloric Sweeteners in Children: A Controversial Theme.

Noncaloric sweeteners (NCS) are food additives used to provide sweetness without adding calories. Their consumption has become more widespread around the world in all age groups, including children. The aim of this study is to show the state of the art about the intake of noncaloric sweeteners in children, as well as their benefits and consumption risk. Scientific searchers were used (PUBMED, Scopus, and Scielo) to analyze articles that included keywords (noncaloric sweeteners/saccharin/cyclamate/acesulfame potassium/aspartame/sucralose/stevia/children) in English, Spanish, and Portuguese. Authors conclude that it is imperative that health professionals judiciously and individually evaluate the overall benefits and risks of NCS use in consumers before recommending their use. Different subgroups of the population incorporate products containing NCS in their diet with different objectives, which should be considered when recommending a diet plan for the consumer. In childhood, in earlier age groups, this type of additives should be used as a dietary alternative when other forms of prevention in obesity are not sufficient.

Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats.

In a previous study, we showed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. We now question whether it could be due to the sweet taste of saccharin per se. We also aimed to address if this weight gain is associated with insulin-resistance and to increases in gut peptides such as leptin and PYY in the fasting state. In a 14 week experiment, 16 male Wistar rats received either saccharin-sweetened yogurt or non-sweetened yogurt daily in addition to chow and water ad lib. We measured daily food intake and weight gain weekly. At the end of the experiment, we evaluated fasting leptin, glucose, insulin, PYY and determined insulin resistance through HOMA-IR. Cumulative weight gain and food intake were evaluated through linear mixed models. Results showed that saccharin induced greater weight gain when compared with non-sweetened control (p = 0.027) despite a similar total caloric intake. There were no differences in HOMA-IR, fasting leptin or PYY levels between groups. We conclude that saccharin sweet taste can induce mild weight gain in Wistar rats without increasing total caloric intake. This weight gain was not related with insulin-resistance nor changes in fasting leptin or PYY in Wistar rats.

Artificial sweetener consumption and urinary tract tumors in Cordoba, Argentina.

OBJECTIVE: To determine the role of the habitual use of the most common artificial sweeteners (AS) in the development of urinary tract tumors (UTT) in Argentina. METHODS: Case-control study of 197 patients with histologically confirmed UTT of transitional varieties, and 397 controls with acute, non-neoplastic, and non-urinary tract diseases, admitted to the same hospitals in Córdoba (Argentina) between 1999 and 2006. All subjects were interviewed about their use of AS and their exposure to other known or suspected risk factors for UTT. RESULTS: Fifty-one UTT patients (26%) and 87 controls (22%) used AS. The risk of UTT was significantly increased in long-term (> or =10 years) AS users compared with none-AS users. The OR (95% CI) for long-term consumers was 2.18 (1.22-3.89) and for short-term users was 1.10 (0.61-2.00) after adjustment for age, gender, BMI, social status. and years of tobacco use. CONCLUSION: Regular use of AS for 10 years or more was positively associated with UTT.

Kindling increases aversion to saccharin in taste aversion learning.

Kindling is a model in which an initially subconvulsive electrical stimulation of certain brain areas eventually develops a generalized seizure that produces behavioral and long term neuronal changes. In the present study we evaluated if kindling can modify conditioning taste aversion (CTA). In this paradigm animals acquire aversion to saccharin when it is presented as the conditioned stimulus (CS) followed by an injection of lithium chloride (LiCl) that induces a gastric irritation as the unconditioned stimulus (US). Male Wistar rats were implanted with bipolar electrodes aimed at the right amygdala (AMG) or at the right insular cortex (IC). The animals were stimulated daily until they reached stages 2-4 (intermediate) or until kindling was fully established (three consecutive stage 5 seizures). At least two weeks after kindling stimulation had ceased the animals were deprived of water for 24 h and given 10-min drinking sessions twice a day for 4 days. On day 5 (morning session) tap water was replaced by saccharin solution (0.1%), 20 min later the animals were injected with LiCl (7.5 ml/kg i.p., 0.2 M) to induce gastric malaise or taste aversion. After three more days of baseline consumption, water was substituted by a fresh 0.1% saccharin solution to test the aversion. AMG-kindling delayed the extinction of CTA. Animals with kindling in the IC had a higher retention than the sham kindling group; that is, they drank significantly less saccharin solution than the other groups. The results of the present experiment show that local modification of brain function induced by kindling stimulation can prolong the aversive effects of CTA.

Uso de adoçantes durante a gravidez e ganho de peso gestacional / Intake of sweeteners during pregnancy and maternal weight gain

Durante a gestaçäo ocorre um período de acelerado crescimento, com diversas mudanças bioquímicas e fisiológicas. Nessa fase a mulher torna-se mais vulnerável aos problemas nutricionais devido ao aumento dos requerimentos de nutrientes, que por sua vez podem näo estar sendo atendidos, se forem utilizados produtos dietéticos. O efeito de uma nutriçäo materna inadequada pode ser prejudicial ao feto e consequentemente acarretar complicaçöes adversas, como baixo peso ao nascer, um fator intimamente relacionado com a mortalidade infantil. Atualmente os assuntos relacionados com qualidade de vida vêm tomando espaço atingido das mais diversas formas todos os segmentos da sociedade. Há também um contexto social onde a estética se tornou um fator de extrema importância, tornando a magreza um parâmetro ideal. O comportamento alimentar das pessoas vem se transformando, existindo uma forte tendência de substituir os alimentos tradicionais por produtos que assegurem menor valor calórico. Com a falta de esclarecimento sobre os produtos dietéticos e a verdadeira onda diet que vive o comércio, ocupando cada vez mais os espaços de prateleiras, foi nossa preocupaçäo verificar o uso de adoçantes (edulcorantes), bem como, de alguns produtos que os contenham, por gestantes, tendo em vista ser este um grupo vulnerável, aliado ao aspecto de faltarem estudos conclusivos a respeito do uso de adoçantes e seus possíveis efeitos durante a gestaçäo

Efecto de la sacarina de sodio en el intestino grueso del raton / Sodium saccharin effect in the mice large intestine

Se ha comprobado que la sacarina de sodio es un promotor tumoral del epitelio de la vegija de rata, propiedad no demostrada en el ser humano y actualmente discutida. En este trabajo se describen las alteraciones que produce este edulcorante en el epitelio del colon descendente de ratones cepa C3H, cuando es adicional al alimento en bajas dosis. Se muestra por microscopia electrónica de transmisión, que la sacarina de sodio produce en las células absortivas del epitelio del colon un pleomorfismo microvellositario constituido por microvellosidades de diferente forma, longitud, diámetro y curvatura.

Efecto de la sacarina de sodio en el intestino grueso del raton / Sodium saccharin effect in the mice large intestine

Se ha comprobado que la sacarina de sodio es un promotor tumoral del epitelio de la vegija de rata, propiedad no demostrada en el ser humano y actualmente discutida. En este trabajo se describen las alteraciones que produce este edulcorante en el epitelio del colon descendente de ratones cepa C3H, cuando es adicional al alimento en bajas dosis. Se muestra por microscopia electrónica de transmisión, que la sacarina de sodio produce en las células absortivas del epitelio del colon un pleomorfismo microvellositario constituido por microvellosidades de diferente forma, longitud, diámetro y curvatura. (AU)

[Sodium saccharin effect on the mice large intestine]. / Efecto de la sacarina de sodio en el intestino grueso del ratón.

Sodium saccharin has found to be a tumoral promoter in the rat's bladder epithelium, property not demonstrated in humans. Nevertheless, at present there's no references on the possible alterations produced by sodium saccharin in the epithelium of the mice colon. In this work we describe the alterations produced by low doses of sodium saccharin in the epithelium of the mice colon. The changer produced by sodium saccharin consist in pleomorphic microvill with variations of form, length diameter and curvature and demonstrate by transmission electron microscopy.

Erupción fija pigmentaria por jugos artificiales / Fixed pigmentary drug eruption due to artificial juices

Se presentan tres pacientes entre siete y once años de edad, que desarrollaron una erupción fija pigmentaria tras al ingesta durante más de tres años de jugos artificiales dietéticos. Se realizó estudio histológico, que fue de compatibilidad en el primer y segundo caso, mostrando un patrón liquenoide en el tercero. Se discute el rol de los edulcorantes contenidos en estos jugos artificiales, como así su asociación con las sulfas

Erupción fija pigmentaria por jugos artificiales / Fixed pigmentary drug eruption due to artificial juices

Se presentan tres pacientes entre siete y once años de edad, que desarrollaron una erupción fija pigmentaria tras al ingesta durante más de tres años de jugos artificiales dietéticos. Se realizó estudio histológico, que fue de compatibilidad en el primer y segundo caso, mostrando un patrón liquenoide en el tercero. Se discute el rol de los edulcorantes contenidos en estos jugos artificiales, como así su asociación con las sulfas (AU)

[Changes in cytomembrane and surface cells of the large intestine resulting from the action of sweetening agents]. / Alteraciones en la citomembrana y células de superficie del intestino grueso por acción de los edulcorantes.

Saccharin and cyclamates have been proved to cause organic damage. This work attempt to describe drug-induced changes brought about by drugs in 1/1000 saccharin and cyclamate-fed rats for 90 days. The ultrastructural findings show: microvilli hypertrophy; membranous mitochondrial increase in absorptive cells; and secretion changes in calciform cells. Such changes are cell-response phenomena to interference or mutagenic action on nuclear DNA or on cytoplasmatic metabolism.

Alteraciones en la citomembrana y celulas de superficie del intestino grueso por accion de los edulcorantes / Changes of cytomembrane and surface cells of the large intestine by sweetening agents action

Se ha demostrado que la sacarina y los ciclamatos provocan lesiones en el organismo. Describimos en este trabajo las alteraciones producidas por estas drogas en ratones alimentados con una solución de sacarina y ciclamato al 1/1000, durante 90 días. El estudio ultraestructural revela: Hipertrofia microvellositaria e incremento membranoso mitocondrial en las células absortivas y alteraciones en la secreción de células calciformes. Estas modificaciones son fenómenos de respuesta celular por interferencia o acción mutágena sobre el ADN nuclear o metabolismo citoplasmático. Los autores agradecen a la señora Carolina S. de Santolaya por el apoyo técnico realizado. Esta investigación fue apoyada financieramente por el Consejo de Investigación de la Unviersidad Nacional de Tucumán

Alteraciones en la citomembrana y celulas de superficie del intestino grueso por accion de los edulcorantes / Changes of cytomembrane and surface cells of the large intestine by sweetening agents action

Se ha demostrado que la sacarina y los ciclamatos provocan lesiones en el organismo. Describimos en este trabajo las alteraciones producidas por estas drogas en ratones alimentados con una solución de sacarina y ciclamato al 1/1000, durante 90 días. El estudio ultraestructural revela: Hipertrofia microvellositaria e incremento membranoso mitocondrial en las células absortivas y alteraciones en la secreción de células calciformes. Estas modificaciones son fenómenos de respuesta celular por interferencia o acción mutágena sobre el ADN nuclear o metabolismo citoplasmático. Los autores agradecen a la señora Carolina S. de Santolaya por el apoyo técnico realizado. Esta investigación fue apoyada financieramente por el Consejo de Investigación de la Unviersidad Nacional de Tucumán (AU)

Tobacco smoking, occupational exposure and bladder cancer in Argentina.

The highest rate for bladder cancer in Latin America has been reported from La Plata, Argentina. A case-control study was carried out to investigate the reasons for this high rate. A total of 117 cases, 117 hospital controls and 117 neighbourhood sex- and age-matched controls were interviewed regarding their smoking and drinking habits and occupational exposures. Cigarette smoking and coffee drinking were identified as the major risk factors, and a significant association was also found for truck and railway drivers and for oil refinery workers. The relative risks for male smokers who ever smoked cigarettes vs. non-smokers was 4.3 (95% Cl: 1.9-10.3). The risk associated with black tobacco cigarettes was 2-3 times higher than that of blond cigarettes. For male ex-smokers the risk after 5 years of no smoking is less than one third of that of current smokers. The RR for drinking coffee was 2.4 (95% Cl: 1.4-4.4) after adjusting for the effects of tobacco smoking, and the risk increased with the number of cups per day. No association was found with the use of saccharin.