Sucralose: From Sweet Success to Metabolic Controversies-Unraveling the Global Health Implications of a Pervasive Non-Caloric Artificial Sweetener.

Sucralose is a food additive initially used to mitigate glycemic peaks and calorie intake in patients with diabetes and obesity. Although sucralose has been considered safe for human consumption, the World Health Organization (WHO) issued a global alert in 2023 concerning the potential health implications of this artificial sweetener. This review aims to comprehensively explore the effects of sucralose intake on human health by understanding sucralose absorption, metabolism, and excretion. We also outline the role of the sweet taste 1 receptor 3 (T1R3) in mediating sucralose-dependent signaling pathways that regulate satiety, incretin release, and insulin response. Finally, we discuss the impact of sucralose on microbiome dysbiosis, inflammatory response origin, liver damage, and toxicity. Gaining a deeper understanding of the manifold effects of sucralose on human physiology will help promote further studies to ensure its consumption is deemed safe for a broader population, including children, adolescents, and pregnant women.

Molecular mechanisms involved in fetal programming and disease origin in adulthood.

Fetal programming occurs during the gestational age when exposure to environmental stimuli can cause long-term changes in the fetus, predisposing it to develop chronic non-communicable diseases (CNCD) in adulthood. Herein, we summarized the role of low-calorie or high-fat diets during pregnancy as fetal programming agents that induce intrauterine growth restriction (IUGR), amplified de novo lipogenesis, and increased amino acid transport to the placenta, which favor the CNCD onset in the offspring. We also outlined how maternal obesity and gestational diabetes act as fetal programming stimuli by reducing iron absorption and oxygen transport to the fetus, stimulating inflammatory pathways that boost neurological disorders and CNCD in the progeny. Moreover, we reviewed the mechanisms through which fetal hypoxia elevates the offspring's risk of developing hypertension and chronic kidney disease in adult life by unbalancing the renin-angiotensin system and promoting kidney cell apoptosis. Finally, we examined how inadequate vitamin B12 and folic acid consumption during pregnancy programs the fetus to greater adiposity, insulin resistance, and glucose intolerance in adulthood. A better understanding of the fetal programming mechanisms may help us reduce the onset of insulin resistance, glucose intolerance, dyslipidemia, obesity, hypertension, diabetes mellitus, and other CNCD in the offspring during adulthood.

Newborns from Mothers Who Intensely Consumed Sucralose during Pregnancy Are Heavier and Exhibit Markers of Metabolic Alteration and Low-Grade Systemic Inflammation: A Cross-Sectional, Prospective Study.

Robust data in animals show that sucralose intake during gestation can predispose the offspring to weight gain, metabolic disturbances, and low-grade systemic inflammation; however, concluding information remains elusive in humans. In this cross-sectional, prospective study, we examined the birth weight, glucose and insulin cord blood levels, monocyte subsets, and inflammatory cytokine profile in 292 neonates at term from mothers with light sucralose ingestion (LSI) of less than 60 mg sucralose/week or heavy sucralose intake (HSI) of more than 36 mg sucralose/day during pregnancy. Mothers in the LSI (n = 205) or HSI (n = 87) groups showed no differences in age, pregestational body mass index, blood pressure, and glucose tolerance. Although there were no differences in glucose, infants from HSI mothers displayed significant increases in birth weight and insulin compared to newborns from LSI mothers. Newborns from HSI mothers showed a substantial increase in the percentage of inflammatory nonclassical monocytes compared to neonates from LSI mothers. Umbilical cord tissue of infants from HSI mothers exhibited higher IL-1 beta and TNF-alpha with lower IL-10 expression than that found in newborns from LSI mothers. Present results demonstrate that heavy sucralose ingestion during pregnancy affects neonates' anthropometric, metabolic, and inflammatory features.

Cord blood levels of interleukin-10 decrease in neonates with increased birth weight: novel implications of the cytokine network in early obesity.

Interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) are associated with body weight alterations in children, adolescents, and adults. However, little is known regarding the role of IL-10 and IFN-gamma in birth weight of neonates. One hundred eighty-two infants were enrolled and divided in groups of normal birth weight (< 95th percentile) or increased birth weight (> 95th percentile) for gestational age. IL-10 and IFN-gamma levels were measured in umbilical cord tissue and blood of newborns by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). The average value of birth weight in infants below and above the 95th percentile was 3.03±0.39 and 3.58±0.37 kg, respectively, and was independent of the mother's pre-gestational body mass index. The Student t test revealed that neonates with birth weights > 95th percentile show a significant 30% decrease in cord blood values of IL-10 as compared to infants with birth weights < 95th percentile (P<0.0001), with no significant changes in IFN-gamma levels (P=0.1661). Cord blood IL-10 was not of maternal origin but produced by umbilical cord tissue that showed less IL-10 expression in neonates with birth weights > 95th percentile than in infants with birth weights < 95th percentile (P=0.0252). Cord blood levels of IL-10 exhibited significant inverse correlations with birth weight (r = - 0.658, P=0.002) and INF-gamma (r = - 0.502, P=0.005).Conclusion: In conclusion, this work demonstrates for the first time that cord blood IL-10 decreases as birth weight increases in infants born at term and might help to improve early recognition of newborns at higher risk of developing obesity in childhood or adulthood. What is Known: • Reduction in interleukin-10 levels has been associated with obesity in adolescents and adults but not newborns. • The number of neonates with excess birth weight has alarmingly increased in the last 30 years. What is New: • We demonstrate that umbilical cord blood levels of interleukin-10 clearly decrease as birth weight increases. • Interleukin-10 and interferon-gamma integrate a cytokine network that might play a role in obesity in infants.