RESUMO
SCOPE: The disturbance of the hypothalamic-pituitary-gonadal (HPG) axis, gut microbiota (GM) community, and short-chain fatty acids (SCFAs) is a triggering factor for pubertal onset. The study investigates the effects of the long-term intake of aspartame on puberty and GM in animals and humans. METHODS AND RESULTS: Aspartame-fed female offspring rats result in vaginal opening time prolongation, serum estrogen reduction, and serum luteinizing hormone elevation. , 60 mg kg-1 aspartame treatment decreases the mRNA levels of gonadotropin-releasing hormone (GnRH), Kiss1, and G protein-coupled receptor 54 (GPR54), increases the mRNA level of RFamide-related peptide-3 (RFRP-3), and decreases the expression of GnRH neurons in the hypothalamus. Significant differences in relative bacterial abundance at the genus levels and decreased fecal SCFA levels are noted by 60 mg kg-1 aspartame treatment. Among which, Escherichia-Shigella is negatively correlated with several SCFAs. In girls, high-dose aspartame consumption decreases the risk of precocious puberty. CONCLUSIONS: Aspartame reduces the chance of puberty occurring earlier than usual in female offspring and girls. Particularly, 60 mg kg-1 aspartame-fed female offspring delays pubertal onset through the dysregulation of HPG axis and GM composition by inhibiting the Kiss1/GPR54 system and inducing the RFRP-3. An acceptable dose of aspartame should be recommended during childhood.
Assuntos
Kisspeptinas , Puberdade Tardia , Humanos , Ratos , Feminino , Animais , Kisspeptinas/metabolismo , Kisspeptinas/farmacologia , Aspartame/efeitos adversos , Aspartame/metabolismo , Puberdade Tardia/metabolismo , Ratos Sprague-Dawley , Maturidade Sexual/fisiologia , Hormônio Liberador de Gonadotropina/genética , Hipotálamo/metabolismo , Puberdade , RNA Mensageiro/metabolismoAssuntos
Hemocromatose/induzido quimicamente , Interações Ervas-Drogas , Testes de Função Hepática , Silybum marianum/efeitos adversos , Acetaminofen/efeitos adversos , Acetaminofen/metabolismo , Analgésicos não Narcóticos/efeitos adversos , Analgésicos não Narcóticos/metabolismo , Aspartame/efeitos adversos , Aspartame/metabolismo , Hemocromatose/diagnóstico , Humanos , Silybum marianum/metabolismo , Edulcorantes/efeitos adversos , Edulcorantes/metabolismoRESUMO
The addition of artificial sweeteners to a LAPT (yeast extract, peptone, and tryptone) medium without supplemented sugar increased the growth rate and final biomass of Lactobacillus delbrueckii subsp. bulgaricus YOP 12 isolated from commercial yogurt. Saccharin and cyclamate were consumed during microorganism growth, while the uptake of aspartame began once the medium was glucose depleted. The pH of the media increased as a consequence of the ammonia released into the media supplemented with the sweeteners. The L. delbrueckii subsp. bulgaricus strain was able to grow in the presence of saccharin, cyclamate, or aspartame, and at low sweetener concentrations, the microorganism could utilize cyclamate and aspartame as an energy and carbon source.
Assuntos
Lactobacillus delbrueckii/crescimento & desenvolvimento , Lactobacillus delbrueckii/metabolismo , Edulcorantes/metabolismo , Iogurte/microbiologia , Aspartame/metabolismo , Biomassa , Meios de Cultura/química , Ciclamatos/metabolismo , Relação Dose-Resposta a Droga , Concentração de Íons de Hidrogênio , Cinética , Modelos Biológicos , Sacarina/metabolismoRESUMO
Over 20 years have elapsed since aspartame was approved by regulatory agencies as a sweetener and flavor enhancer. The safety of aspartame and its metabolic constituents was established through extensive toxicology studies in laboratory animals, using much greater doses than people could possibly consume. Its safety was further confirmed through studies in several human subpopulations, including healthy infants, children, adolescents, and adults; obese individuals; diabetics; lactating women; and individuals heterozygous (PKUH) for the genetic disease phenylketonuria (PKU) who have a decreased ability to metabolize the essential amino acid, phenylalanine. Several scientific issues continued to be raised after approval, largely as a concern for theoretical toxicity from its metabolic components--the amino acids, aspartate and phenylalanine, and methanol--even though dietary exposure to these components is much greater than from aspartame. Nonetheless, additional research, including evaluations of possible associations between aspartame and headaches, seizures, behavior, cognition, and mood as well as allergic-type reactions and use by potentially sensitive subpopulations, has continued after approval. These findings are reviewed here. The safety testing of aspartame has gone well beyond that required to evaluate the safety of a food additive. When all the research on aspartame, including evaluations in both the premarketing and postmarketing periods, is examined as a whole, it is clear that aspartame is safe, and there are no unresolved questions regarding its safety under conditions of intended use.
Assuntos
Aspartame/efeitos adversos , Edulcorantes/efeitos adversos , Afeto/efeitos dos fármacos , Animais , Aspartame/administração & dosagem , Aspartame/metabolismo , Aspartame/toxicidade , Comportamento/efeitos dos fármacos , Neoplasias Encefálicas/induzido quimicamente , Cognição/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Hipersensibilidade a Drogas/etiologia , Eletroencefalografia/efeitos dos fármacos , Sistema Endócrino/efeitos dos fármacos , Cefaleia/induzido quimicamente , Humanos , Metanol/metabolismo , Fenilalanina/metabolismo , Vigilância de Produtos Comercializados , Convulsões/induzido quimicamente , Edulcorantes/administração & dosagem , Edulcorantes/metabolismo , Edulcorantes/toxicidade , Redução de Peso/efeitos dos fármacosRESUMO
Since the introduction of aspartame into the American food supply in 1981, it has grown to become the most widely used and accepted artificial sweetener. However, recent published and unpublished reports of headaches, seizures, blindness, and cognitive and behavioral changes with long-term, high-dose aspartame may be cause for concern. Physician awareness of the present clinical and research status of aspartame is important.