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.