Effects of Nonnutritive Sweeteners on the BMI of Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies.

The effect of nonnutritive sweeteners (NNSs) on the body mass index [BMI (in kg/m2)] of children and adolescents remains unclear despite rising consumption. Detailed systematic evaluations are warranted. We aimed to summarize evidence on NNS consumption and BMI sex- and age-specific absolute changes (kg/m2) in pediatric populations, by NNS type, study design, duration, analysis type, conflicts of interest (COI), geographical region, age, sex, and baseline BMI. We searched randomized controlled trials (RCTs) and prospective cohort studies in children (2-9 y), adolescents (10-24 y), and young adults (20-24 y). Pooled estimates derived from random-effects meta-analysis for BMI changes, and the evidence quality was evaluated overall and by subgroup. From 2789 results, we included 4 RCTs [n = 1372; mean follow-up = 42.6 wk (standard deviation = 18.4); 2 (50%) with COI], and 8 prospective cohort studies [n = 35,340; median follow-up 2.5 y (interquartile range = 1.7-6.3), 2 (25%) with COI]. No identified studies evaluated NNS in food, NNS beverages compared with water, or participants aged 20-24 y. Random allocation to NNS beverages (25-2400 mg/d, from beverages) showed less BMI gain [mean difference = -0.114 kg/m2 (95% confidence interval [CI]: -0.207, -0.021); I2 = 87.02%] compared with sugar-sweetened beverages (SSBs). Stratified estimates resulted in less BMI gain in adolescents, participants with baseline obesity, consumers of mixed NNS, longer trials, and trials without COI. Pooled estimates from prospective cohorts showed a nonsignificant association between NNS beverages and BMI gain [0.05 kg/m2 (95% CI: -0.03, 0.13); I2 = 75.06%; per daily 355 mL serving]. Stratified estimates remained consistent. Removing studies with COI attenuated estimates. Evidence had low to moderate quality. In summary, pooled results from RCTs comparing NNS beverages compared with SSBs showed less BMI gain in adolescents with obesity. Meta-analyses of long-term cohort studies did not display a significant association between NNS beverages and BMI changes. This trial was registered at PROSPERO as CRD42022352284.

Association between personality traits, eating behaviors, and the genetic polymorphisms FTO-rs9939609 and MAO-A 30 bp u-VNTR with obesity in Mexican Mayan children.

Introduction: Genetic variants that control dopamine have been associated with obesity in children through loss of control of satiety and impulses, the manifestation of addictive eating behaviors, and specific personality traits. The variants include FTO-rs9939609 and the MAO-A 30 pb u-VNTR low-transcription alleles (LTA). Objective: To evaluate the genetic association of FTO-rs9939609 and the MAO-A LTA, along with personality traits and eating behavior with obesity in Mayan children from Mexico. Methods: We cross-sectionally evaluated 186 children (70 with obesity and 116 with normal weight) 6-12 years old from Yucatan, Mexico. Nutritional status was defined with body mass index (BMI) percentiles. Personality traits were evaluated with the Conners and TMCQ tests; eating behavior was evaluated with the CEBQ test. Genotyping with real-time PCR and TaqMan probes was used for FTO-rs9939609, whereas PCR amplification was used for MAO-A u-VNTR. Results: High-intensity pleasure (p = 0.013) and moderate appetite (p = 0.032) differed according to nutritional status. Heterozygous FTO-rs9939609 T/A children showed higher mean scores of low-intensity pleasure (p = 0.002) and moderate appetite (p = 0.027) than homozygous T/T. Hemizygous boys having MAO-A LTA showed significantly higher mean scores of anxiety (p = 0.001) and impulsivity (p = 0.008). In multivariate models, only LTA alleles of MAO-A explained obesity in boys (OR = 4.44; 95% CI = 1.18-16.63). Conclusion: In the present study, MAO-A u-VNTR alleles were associated with obesity in multivariate models only in boys. These alleles might also have a role in personality traits such as anxiety and impulsivity, which secondly contribute to developing obesity in Mayan boys.

Effects of non-nutritive sweeteners on the BMI of children and adolescents: a systematic review and meta-analysis of randomised controlled trials and prospective cohort studies.

BACKGROUND: Considering the biological variation across subgroups during periods of growth, the role of non-nutritive sweeteners in weight-related outcomes among children and adolescents is unclear. We did a systematic review and meta-analysis to summarise the evidence on experimental and habitual consumption of non-nutritive sweeteners and prospective changes in BMI in paediatric populations. METHODS: We searched eligible (ie, lasting a minimum of 4 weeks) randomised controlled trials of the effect of non-nutritive sweeteners versus non-caloric or caloric comparators on BMI change and prospective cohort studies reporting multivariable-adjusted coefficients for non-nutritive sweetener intake and BMI in children (aged 2-9 years) and adolescents (aged 10-24 years). We generated pooled estimates using random effects meta-analysis and did secondary stratified analyses to explore heterogeneity by study-level and subgroup characteristics. We further evaluated the quality of the included evidence and classified industry-funded studies, or those whose authors were related to the food industry, as having potential conflicts of interest. FINDINGS: From 2789 results, we included five randomised controlled trials (n=1498 participants; median follow-up 19·0 weeks [IQR 13·0-37·5]); three [60%] with potential conflicts of interest), and eight prospective cohort studies (n=35 340 participants; median follow-up 2·5 years [IQR 1·7-6·3]; two [25%] with potential conflicts of interest). Random allocation to intake of non-nutritive sweeteners (25-2400 mg/day, from food and beverages) suggested less BMI gain (standardised mean difference -0·42 kg/m2 [95% CI -0·79 to -0·06]; I2=89%) compared with intake of sugar from food and beverages. Stratified estimates were significant only in adolescents, participants with obesity at baseline, consumers of a mixture of non-nutritive sweeteners, longer trials, and trials not found to have potential conflicts of interest. No randomised controlled trials tested beverages containing non-nutritive sweeteners versus water. Prospective cohorts reported a non-significant association between consumption of beverages containing non-nutritive sweeteners and BMI gain (0·05 kg/m2 [95% CI -0·02 to 0·12]; I2=67%; per daily serving of 355 mL), which was accentuated for adolescents, boys, and cohorts with longer follow-ups. Removing studies with potential conflicts of interest attenuated the estimates. Evidence was predominantly classified as of low to moderate quality. INTERPRETATION: Intake of non-nutritive sweeteners versus sugar in randomised controlled trials resulted in less BMI gain in adolescents and participants with obesity. Better designed studies should contrast beverages containing non-nutritive sweeteners with water. Long-term prospective analyses with changes in repeated measures might clarify the effect of intake of non-nutritive sweeteners on BMI changes in childhood and adolescence. FUNDING: None.

Season affects active metabolite composition and cytotoxic effect in Phoradendron wattii methanol extracts.

Plant-derived secondary metabolites are a source of promising bioactive molecules in the search for safer more selective cancer drugs. Mexico's flora is extremely diverse and many species, such as Phoradendron wattii, form part of traditional medicine. Compounds with notable cytotoxic activity have been isolated from P. wattii, but their concentrations may vary seasonally. The aim was to identify any variation in active metabolite concentrations in Phoradendron wattii methanol extracts in response to season. Betulin exhibited the most evident seasonal variations, being most abundant during the midsummer drought. Cytotoxic activity was highest (29 ± 1 µg/mL) in the rainy season methanol extract. Though not the most abundant metabolite in the extracts, 3α,24-dihydroxylup-20(29)-en-28-oic acid is apparently one of the most active among them and is a promising chemotaxonomic biomarker for this species. In summary, secondary metabolite concentrations in P. wattii methanol extracts varied in response to season, and these variations influenced cytotoxic activity.

Tamoxifen side effects: pharmacogenetic and clinical approach in Mexican mestizos.

BACKGROUND: Tamoxifen metabolism is translated into four genetic phenotypes (GP): genetic poor metabolizer (gPM); genetic intermediate metabolizer (gIM); genetic normal metabolizer (gNM); and genetic ultra-rapid metabolizer (gUM). Although CYP2D6 is involved in tamoxifen biotransformation, its association with tamoxifen side effects (TSE) is limited. Therefore, we evaluated CYP2D6 GP and clinical variables as potential predictors of TSE in Mexican Mestizo patients. METHODS: This cross-sectional study evaluated CYP2D6 GP, clinical data, and self-reported TSE in 71 women. Potential predictors were tested in uni- and multivariable models. RESULTS: Hot flashes (57.75%), arthralgia (45.07%), headache (43.66%), and cramps (39.44%) were the most frequent TSE. Three GP were identified: gPM (2.8%); gNM (93.0%); and gUM (4.2%). In the univariate analysis, none of the GP was predictive of TSE. However, the uni- and multivariable models showed contraceptive use and chemotherapy treatment prior to tamoxifen therapy to be predictive. Two alleles were identified for the first time at unusually high frequencies: CYP2D6*34 (13.2%); and *39 (14.7%). CONCLUSIONS: Our findings indicate that CYP2D6 GP were not significantly predictive of TSE, though two clinical descriptors were. The present results are a valuable contribution to pharmacogenetic characterization of Mexican Mestizo populations who, like other Latin-American groups, are poorly represented in the literature.

Development of a high-performance liquid chromatography method with fluorescence detection for the routine quantification of tamoxifen, endoxifen and 4-hydroxytamoxifen in plasma from breast cancer patients.

To date, several methods for the quantification of tamoxifen and its metabolites have been developed, most of which employ liquid chromatography tandem-mass spectrometry (LC-MS/MS). These methods are highly sensitive and reproducible, but are also time-consuming and require expensive equipment; one of their main disadvantages is matrix ionization effects. A more viable option, particularly in developing countries, is high-performance liquid chromatography coupled with UV or fluorescence detection. We developed and validated a method for simultaneous quantification of tamoxifen, endoxifen and 4-hydroxytamoxifen based on high-performance liquid chromatography with fluorescence detection in a reverse-phase column. The method is rapid (16 min plus 5 min of column re-equilibrium), accurate (80-100%) and precise (0.23-6.00%), and does not require any additional irradiation process. Sample pretreatment consists of protein precipitation with acetonitrile under alkaline conditions, employing only 200 µL plasma. The validated method's wide range allowed quantification of steady-state levels in patients under standard tamoxifen treatment (20 mg/day). This assay is ready for application in clinical studies and routine quantification of tamoxifen, endoxifen and 4-hydroxytamoxifen in healthcare institutions.

Healthcare delay in breast cancer patients: a case study in a low-density population region from Mexico.

AIM: To describe delay intervals, their impact on clinical stage and initiation of first oncologic treatment, and evaluate associated factors in breast cancer patients in Yucatan, Mexico, a low-density population region. PATIENTS & METHODS: A retrospective analysis was done of 92 medical records, and bivariate and multivariate models applied to identify associations between healthcare delay and several factors. RESULTS: System delay accounted for most of the delay (median: 86 days; 61% of delay). Socioeconomic status and delivery to tertiary-care hospital predicted delay. Clinical stage determined initiation of first oncologic treatment. CONCLUSION: Delay in treatment was largely due to system delay. Only a few variables explained this delay. Clinical stage had the strongest effect on initiation of first oncologic treatment.