[Non-caloric sweeteners in women of reproductive age - A consensus document]. / Edulcorantes no calóricos en la mujer en edad reproductiva: documento de consenso.

INTRODUCTION: Non-nutritive sweeteners (NNS) are food additives that have been used as a possible tool to reduce energy and sugar intake. There is a scientific debate around the real benefits of their use. NNS are substances widely evaluated in the scientific literature. Their safety is reviewed by international regulatory health agencies. Health professionals and consumers often lack education and objective information about food additives based on the best scientific evidence. NNS have been used as a substitute for sucrose, especially by people with diabetes mellitus and obesity. However, concerns related to their possible association with preterm birth have been raised, and also with their use during pregnancy and lactation because of the possibility of metabolic or other consequences in both the mother and offspring. This analysis of the evidence in gynecology and obstetrics presents a review of the most commonly asked questions regarding this matter by health professionals and their patients. This document evaluates a diversity of scientific publications under the sieve of evidence-based medicine and the regulatory framework for food additives to elucidate whether the use of NNS in women in these critical stages of pregnancy and breastfeeding represents a potential risk.

INTRODUCCIÓN: Los edulcorantes no calóricos (ENC) son aditivos de alimentos que se utilizan para sustituir azúcares y potencialmente para reducir la ingesta energética. Existe un debate científico en torno a los beneficios reales de su uso. Los ENC son sustancias ampliamente evaluadas en la literatura científica. Su seguridad es revisada por las agencias regulatorias internacionales del campo de la salud. Los profesionales de la salud y los consumidores con frecuencia carecen de educación e información rigurosa, objetiva y sustentada en la evidencia científica y el juicio clínico sobre el uso de aditivos en los alimentos. Los ENC se han empleado como sustitutos de la sacarosa, en especial por las personas con diabetes mellitus y obesidad. Sin embargo, se han planteado inquietudes relacionadas con su posible asociación con el parto pretérmino y con su uso durante el embarazo y la lactancia, ante la posibilidad de consecuencias metabólicas o de otra índole en la madre o en el neonato. Este análisis de la evidencia en ginecología y obstetricia presenta una revisión que intenta responder a preguntas que habitualmente se hacen al respecto los profesionales de la salud y sus pacientes. En este documento se evalúan diversas publicaciones científicas bajo el tamiz de la medicina basada en la evidencia y del marco regulatorio para aditivos de alimentos con el fin dilucidar si el uso de ENC en las mujeres durante las etapas críticas del embarazo y la lactancia supone o no un posible riesgo.

The Use of Nonnutritive Sweeteners in Children.

The prevalence of nonnutritive sweeteners (NNSs) in the food supply has increased over time. Not only are more children and adolescents consuming NNSs, but they are also consuming a larger quantity of NNSs in the absence of strong scientific evidence to refute or support the safety of these agents. This policy statement from the American Academy of Pediatrics is intended to provide the pediatric provider with a review of (1) previous steps taken for approved use of NNSs, (2) existing data regarding the safety of NNS use in the general pediatric population, (3) what is known regarding the potential benefits and/or adverse effects of NNS use in children and adolescents, (4) identified gaps in existing knowledge and potential areas of future research, and (5) suggested talking points that pediatricians may use when discussing NNS use with families.

What we know--and don't--about non-nutritive sweeteners.

Here's what's known about the safety of these sweeteners and their effect on weight, appetite, and the risk for type 2 diabetes.

Oral and Systemic Effects of Xylitol Consumption.

Recent results of randomized trials testing the efficacy of xylitol in caries prevention have been conflicting. This narrative review reveals the sources of discrepancy. The following databases were searched for the terms "xylitol" or "artificial sweeteners" restricted to the English language: PubMed, Web of Science, Evidenced-Based Medicine, Scopus, and the Cochrane database. In a separate search, the terms "dental caries" or "cariogenicity" or "glucosyltransferase" or "low glycemic" or "low insulinemic" or "dysbiosis" or "gut microbiome" were used and then combined. In section I, findings regarding the role of xylitol in dental caries prevention, the appropriateness of research methods, and the causes for potential biases are summarized. In section II, the systemic effects of xylitol on gut microbiota as well as low-glycemic/insulinogenic systemic effects are evaluated and summarized. The substitution of a carbonyl group with an alcohol radical in xylitol hinders its absorption and slowly releases sugar into the bloodstream. This quality of xylitol is beneficial for diabetic patients to maintain a constant glucose level. Although this quality of xylitol has been proven in in vitro and animal studies, it has yet to be proven in humans. Paradoxically, recent animal studies reported hyperglycemia and intestinal dysbiosis with artificial sweetener consumption. Upon careful inspection of evidence, it was revealed that these reports may be due to misinterpretation of original references or flaws in study methodology. Any systemic benefits of xylitol intake must be weighed in consideration with the well-established adverse gastrointestinal consequences. The contribution of xylitol to gut dysbiosis that may affect systemic immunity warrants further research.

Metabolic Effects of Low-Calorie Sweeteners: A Brief Review.

Low-calorie sweeteners (LCS) are found in a variety of foods and beverages, yet their role in diet, weight, and obesity-related chronic disease is controversial. This article summarizes proceedings from one of four presentations during a preconference session entitled "Low-Calorie Sweeteners and Weight Management," which took place at the 2017 Obesity Society Annual Meeting in Washington, District of Columbia. The objective of this brief review is to summarize findings of observational and interventional studies of LCS effects on weight and metabolic health and to provide potential explanations for their discrepant results. Key research priorities for advancing the understanding of the role of LCS in weight and chronic disease are also discussed. The existing literature suggests that LCS consumption is consistently associated with obesity, diabetes, and related cardiometabolic conditions in observational studies. Although several plausible mechanisms have been proposed to explain these associations and have received considerable support in cellular and rodent models, the relevance of these mechanisms to humans has yet to be confirmed. Meanwhile, randomized controlled trials demonstrate that NNS may benefit weight loss and weight maintenance. This is the case particularly when LCS are administered in the context of behavioral weight loss support and are consumed knowingly by habitual LCS consumers. Although these findings suggest that LCS may be useful for weight control among those cognitively engaged in weight loss and who are aware of their LCS consumption, LCS administration in these studies does not reflect typical consumption. Furthermore, few interventional studies have assessed the role of LCS on metabolic outcomes other than body weight. Additional factors must be considered before recommending LCS for weight management and chronic disease prevention and further study of LCS effects on a variety of cardiometabolic outcomes, including visceral adiposity and glucose homeostasis is warranted.

Nonnutritive Sweeteners in Weight Management and Chronic Disease: A Review.

OBJECTIVE: The objective of this review was to critically review findings from recent studies evaluating the effects of nonnutritive sweeteners (NNSs) on metabolism, weight, and obesity-related chronic diseases. Biologic mechanisms that may explain NNS effects will also be addressed. METHODS: A comprehensive review of the relevant scientific literature was conducted. RESULTS: Most cross-sectional and prospective cohort studies report positive associations between NNS consumption, body weight, and health conditions, including type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease. Although findings in cellular and rodent models suggest that NNSs have harmful effects on metabolic health, most randomized controlled trials in humans demonstrate marginal benefits of NNS use on body weight, with little data available on other metabolic outcomes. CONCLUSIONS: NNS consumption is associated with higher body weight and metabolic disease in observational studies. In contrast, randomized controlled trials demonstrate that NNSs may support weight loss, particularly when used alongside behavioral weight loss support. Additional long-term, well-controlled intervention studies in humans are needed to determine the effects of NNSs on weight, adiposity, and chronic disease under free-living conditions.

Replacement of glycaemic carbohydrates by inulin-type fructans from chicory (oligofructose, inulin) reduces the postprandial blood glucose and insulin response to foods: report of two double-blind, randomized, controlled trials.

PURPOSE: Inulin-type fructans are recognized as prebiotic dietary fibres and classified as non-digestible carbohydrates that do not contribute to glycaemia. The aim of the present studies was to investigate the glycaemic response (GR) and insulinaemic response (IR) to foods in which sucrose was partially replaced by inulin or oligofructose from chicory. METHODS: In a double-blind, randomized, controlled cross-over design, 40-42 healthy adults consumed a yogurt drink containing oligofructose or fruit jelly containing inulin and the respective full-sugar variants. Capillary blood glucose and insulin were measured in fasted participants and at 15, 30, 45, 60, 90, and 120 min after starting to drink/eat. For each test food, the incremental area under the curve (iAUC) for glucose and insulin was calculated and the GR and IR determined. RESULTS: Consumption of a yogurt drink with oligofructose which was 20% reduced in sugars significantly lowered the glycaemic response compared to the full-sugar reference (iAUC120min 31.9 and 37.3 mmol/L/min, respectively; p < 0.05). A fruit jelly made with inulin and containing 30% less sugars than the full-sugar variant likewise resulted in a significantly reduced blood glucose response (iAUC120min 53.7 and 63.7 mmol/L/min, respectively; p < 0.05). In both studies, the postprandial insulin response was lowered in parallel (p < 0.05). The reduction of postprandial glycaemia was positively correlated to the proportion of sugars replaced by inulin-type fructans (p < 0.001). CONCLUSIONS: In conclusion, the studies confirmed that substitution of glycaemic sugars by inulin or oligofructose from chicory may be an effective strategy to reduce the postprandial blood glucose response to foods.

EffectS of non-nutritive sWeetened beverages on appetITe during aCtive weigHt loss (SWITCH): Protocol for a randomized, controlled trial assessing the effects of non-nutritive sweetened beverages compared to water during a 12-week weight loss period and a follow up weight maintenance period.

BACKGROUND: Acute and medium-term intervention studies suggest that non-nutritive sweeteners (NNS) are beneficial for weight loss, however there is limited human data on the long-term effects of consuming NNS on weight loss, maintenance, and appetite. Further research is therefore required to elucidate the prolonged impact of NNS consumption on these outcome measures. METHODS/DESIGN: A randomized parallel groups design will be used to assess whether regular NNS beverage intake is equivalent to a water control in promoting weight loss over 12-weeks (weekly weight loss sessions; Phase I), then supporting weight maintenance over 40-weeks (monthly sessions; Phase II) and subsequently independent weight maintenance over 52-weeks (Phase III) in 432 participants. A subset of these participants (n=116) will complete laboratory-based appetite probe days (15 sessions; 3 sessions each at baseline, at the start of phase I and the end of each phase). A separate subset (n=50) will complete body composition scans (DXA) at baseline and at the end of each phase. All participants will regularly be weighed and will complete questionnaires and cognitive tasks to assess changes in body weight and appetitive behaviours. Measures of physical activity and biochemical markers will also be taken. DISCUSSION: The trial will assess the efficacy of NNS beverages compared to water during a behavioural weight loss and maintenance programme. We aim to understand whether the impact of NNS on weight, dietary adherence and well-being are beneficial or transient and effects on prolonged successful weight loss and weight maintenance through sustained changes in appetite and eating behaviour. TRIAL REGISTRATION: Clinical Trials: NCT02591134; registered: 23.10.2015.

Sugar replacers: from technological challenges to consequences on health.

PURPOSE OF REVIEW: Dietary sugars play a role in noncommunicable diseases and represent a clear target for reduction. In this context, product reformulation can have a positive impact on health. Several technological solutions are available to replace sugar, all with benefits and limitations. The goal of this review is to describe the main sugar replacement alternatives and discuss their impact on health and product physicochemical properties. RECENT FINDINGS: Although high intensity sweeteners and polyols have been used for a long time to replace sucrose and despite no clear evidence of harm, the trend is today to look for alternatives such as sweet enhancers or alternative sugars such as allulose or tagatose, which are both low caloric. To replace the physical properties of sugars, new trends are to substitute widely used maltodextrins by dietary fibres to confer added health benefits. SUMMARY: A wide range of solutions is currently available to replace dietary sugars and compensate for the impact on bulking properties and sweetness profile of food products.

The paradox of artificial sweeteners in managing obesity.

The role of artificial sweeteners in the management of obesity is controversial. Observational data have suggested that nonnutritive sweeteners (NNSs) may promote weight gain through poorly understood mechanisms of cravings, reward phenomenon, and addictive behavior via opioid receptors. Interventional studies suggest the opposite that substitution of NNS for sugar-sweetened beverages (SSBs) results in reduced caloric intake and modest degrees of weight loss. Whether the use of NNS provides benefit toward weight reduction in the individual patient may depend on the characteristics of their baseline diet, associated changes, or dietary compensation involved with ingestion of NNS, and the degree of compliance with a more complete weight loss program.

Aspartame Administration and Insulin Treatment Altered Brain Levels of CYP2E1 and CYP3A2 in Streptozotocin-Induced Diabetic Rats.

This study demonstrates that aspartame consumption and insulin treatment in a juvenile diabetic rat model leads to increase in cytochrome P450 (CYP) 2E1 and CYP3A2 isozymes in brain. Diabetes mellitus was induced in postweaned 21-day-old Wistar male rat by streptozotocin. Animals were randomly assigned to one of the following groups: untreated control, diabetic (D), D-insulin, D-aspartame, or the D-insulin + aspartame-treated group. Brain and liver tissue samples were used to analyze the activity of CYP2E1 and CYP3A2 and protein levels. Our results indicate that combined treatment with insulin and aspartame in juvenile diabetic rats significantly induced CYP2E1 in the cerebrum and cerebellum without modifying it in the liver, while CYP3A2 protein activity increased both in the brain and in the liver. The induction of CYP2E1 in the brain could have important in situ toxicological effects, given that this CYP isoform is capable of bioactivating various toxic substances. Additionally, CYP3A2 induction in the liver and brain could be considered a decisive factor in the variation of drug response and toxicity.

Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohort studies.

BACKGROUND: Replacement of caloric sweeteners with lower- or no-calorie alternatives may facilitate weight loss or weight maintenance by helping to reduce energy intake; however, past research examining low-calorie sweeteners (LCSs) and body weight has produced mixed results. OBJECTIVE: The objective was to systematically review and quantitatively evaluate randomized controlled trials (RCTs) and prospective cohort studies, separately, that examined the relation between LCSs and body weight and composition. DESIGN: A systematic literature search identified 15 RCTs and 9 prospective cohort studies that examined LCSs from foods or beverages or LCSs consumed as tabletop sweeteners. Meta-analyses generated weighted mean differences in body weight and composition values between the LCS and control groups among RCTs and weighted mean correlations for LCS intake and these parameters among prospective cohort studies. RESULTS: In RCTs, LCSs modestly but significantly reduced all outcomes examined, including body weight (-0.80 kg; 95% CI: -1.17, -0.43), body mass index [BMI (in kg/m²): -0.24; 95% CI: -0.41, -0.07], fat mass (-1.10 kg; 95% CI: -1.77, -0.44), and waist circumference (-0.83 cm; 95% CI: -1.29, -0.37). Among prospective cohort studies, LCS intake was not associated with body weight or fat mass, but was significantly associated with slightly higher BMI (0.03; 95% CI: 0.01, 0.06). CONCLUSIONS: The current meta-analysis provides a rigorous evaluation of the scientific evidence on LCSs and body weight and composition. Findings from observational studies showed no association between LCS intake and body weight or fat mass and a small positive association with BMI; however, data from RCTs, which provide the highest quality of evidence for examining the potentially causal effects of LCS intake, indicate that substituting LCS options for their regular-calorie versions results in a modest weight loss and may be a useful dietary tool to improve compliance with weight loss or weight maintenance plans.

Structure and biological properties of lentztrehalose: a novel trehalose analog.

A new trehalose analog, lentztrehalose [4-O-(2,3-dihydroxy-3-methylbutyl)trehalose], was isolated from an actinomycete Lentzea sp. Lentztrehalose is only weakly hydrolyzed by the trehalose-hydrolyzing enzyme, trehalase, so can be regarded as an enzyme-stable analog of trehalose. Although lentztrehalose does not show apparent toxicity to mammalian cells and microbes, it has antitumor activity in mice bearing S-180 sarcoma and Ehrlich carcinoma cells. In ovariectomized mice, lentztrehalose displayed a bone reinforcement effect in the femur that was superior to trehalose and induced non-morbid suppression of weight gain comparable with trehalose. These results indicate that enzyme-stable analogs of trehalose, such as lentztrehalose, may be more beneficial for human health and thus have potential as substitutes for trehalose as a sweetener.