Consumption of aspartame and other artificial sweeteners and risk of cancer in the Spanish multicase-control study (MCC-Spain)

Use of artificial sweeteners (AS) such as aspartame, cyclamate, saccharin and sucralose is widespread. We evaluated the association of use of aspartame and other AS with cancer. In total 1881 colorectal, 1510 breast, 972 prostate and 351 stomach cancer and 109 chronic lymphocytic leukaemia (CLL) cases and 3629 population controls from the Spanish Multicase-Control (MCC-Spain) study were recruited (2008-2013). The consumption of AS, from table-top sweeteners and artificially sweetened beverages, was assessed through a self-administered and validated food frequency questionnaire (FFQ). Sex-specific quartiles among controls were determined to compare moderate consumers (<third quartile) and high consumers (≥ third quartile) vs non consumers (reference category), distinguishing aspartame-containing products and other AS. Unconditional logistic regression models were used to estimate adjusted OR and 95%CI, and results were stratified by diabetes status. Overall, we found no associations between the consumption of aspartame or other AS and cancer. Among participants with diabetes, high consumption of other AS was associated with colorectal cancer (OR = 1.58, 95% CI 1.05-2.41, P trend = .03) and stomach cancer (OR = 2.27 [0.99-5.44], P trend = .06). High consumption of aspartame, was associated with stomach cancer (OR = 2.04 [0.7-5.4], P trend = .05), while a lower risk was observed for breast cancer (OR = 0.28 [0.08-0.83], P trend = .03). In some cancers, the number of cases in participants with diabetes were small and results should be interpreted cautiously. We did not find associations between use of AS and cancer, but found associations between high consumption of aspartame and other AS and different cancer types among participants with diabetes.The study was partially funded by the “Accion Transversal del Cancer”, approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI17CIII/00034), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad [MINECO] through the Instituto de Salud Carlos III [ISCIII] and Red Temática de Investigación del Cáncer [RTICC] del ISCIII [RD12/0036/0036]), by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra), by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the Catalan Government-Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723, 2014SGR850, 2017SGR1085, 2021SGR01354 by the Fundaci on Caja de Ahorros de Asturias and by the University of Oviedo. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. Anna Palomar-Cros is supported by a MINECO (Spanish Ministry of Economy) fellowship (PRE2019-089038). Camille Lassale is supported by a Ramon y Cajal Fellowship RYC2020-029599 funded by MCIN (Spanish Ministry of Science and Innovation) and EI FSE “Invest in your future".Departamento de Física Aplicad

Deep Diving Into the Cardiovascular Health Paradox: A Journey Towards Personalized Prevention

ObjectivesThe Life’s Simple 7 score (LS7) promotes cardiovascular health (CVH). Despite this, some with optimal LS7 develop cardiovascular disease (CVD), while others with poor CVH do not, termed the “CVH paradox.” This paper explores pathways explaining this paradox.MethodsWe examined methodological aspects: 1) misclassification bias in self-reported lifestyle factors (smoking, physical activity, diet); 2) cumulative exposure to risk factors over a lifetime, impacting the CVH paradox. Punctual risk factor assessments are suboptimal for predicting outcomes. We proposed personalized prevention using “novel” elements to refine CVH assessment: 1) subclinical vascular disease markers, 2) metabolic biomarkers in blood and urine, 3) emerging risk factors, 4) polygenic risk scores (PRS), 5) epigenetics, and 6) the exposome.ResultsAddressing the CVH paradox requires a multifaceted approach, reducing misclassification bias, considering cumulative risk exposure, and incorporating novel personalized prevention elements.ConclusionA holistic, individualized approach to CVH assessment and CVD prevention can better reduce cardiovascular outcomes and improve population health. Collaboration among researchers, healthcare providers, policymakers, and communities is essential for effective implementation and realization of these strategies

Overweight, obesity, and individual symptoms of depression : A multicohort study with replication in UK Biobank

Objectives: Obesity is associated with increased risk of depression, but the extent to which this association is symptom-specific is unknown. We examined the associations of overweight and obesity with individual depressive symptoms. Methods: We pooled data from 15 population-based cohorts comprising 57,532 individuals aged 18 to 100 years at study entry. Primary analyses were replicated in an independent cohort, the UK Biobank study (n = 122,341, age range 38 to 72). Height and weight were assessed at baseline and body mass index (BMI) was computed. Using validated self-report measures, 24 depressive symptoms were ascertained once in 16 cross-sectional, and twice in 7 prospective cohort studies (mean follow-up 3.2 years). Results: In the pooled analysis of the primary cohorts, 22,045 (38.3 %) participants were overweight (BMI between 25 and 29.9 kg/m(2)), 12,025 (20.9 %) class I obese (BMI between 30 and 34.9 kg/m(2)), 7,467 (13.0 %) class II-III obese (BMI >= 35 kg/m(2)); and 7,046 (12.3 %) were classified as depressed. After multivariable adjustment, obesity class I was cross-sectionally associated with 1.11-fold (95 % confidence interval 1.01-1.22), and obesity class II-III with 1.31-fold (1.16-1.49) higher odds of overall depression. In symptom-specific analyses, robust associations were apparent for 4 of the 24 depressive symptoms ('could not get going/lack of energy', 'little interest in doing things', 'feeling bad about yourself, and 'feeling depressed'), with confounder-adjusted odds ratios of having 3 or 4 of these symptoms being 1.32 (1.10-1.57) for individuals with obesity class I, and 1.70 (1.34-2.14) for those with obesity class II-III. Elevated C-reactive protein and 21 obesity-related diseases explained 23 %-31 % of these associations. Symptom-specific associations were confirmed in longitudinal analyses where obesity preceded symptom onset, were stronger in women compared with men, and were replicated in UK Biobank. Conclusions: Obesity is associated with a distinct set of depressive symptoms. These associations are partially explained by systemic inflammation and obesity-related morbidity. Awareness of this obesity-related symptom profile and its underlying biological correlates may inform better targeted treatments for comorbid obesity and depression.Peer reviewe

Blood DNA methylation signature of diet quality, and association with cardiometabolic traits

BACKGROUND: Diet quality might influence cardiometabolic health through epigenetic changes, but this has been little investigated in adults. Our aim was to identify Cytosine-phosphate-Guanine (CpG) dinucleotides associated with diet quality by conducting an epigenome-wide association study (EWAS) based on blood DNA methylation (DNAm), and to assess how diet-related CpGs associate with inherited susceptibility to cardiometabolic traits: body mass index (BMI), systolic blood pressure (SBP), triglycerides, type 2 diabetes (T2D) and coronary heart disease (CHD). METHODS: Meta-EWAS including 5,274 participants in four cohorts from Spain, the US and the UK. We derived three dietary scores (exposures) to measure adherence to a Mediterranean diet (MMDS), to a healthy plant-based diet (HPDI) and to the Dietary Approaches to Stop Hypertension (DASH). Blood DNAm (outcome) was assessed with the Infinium arrays Human Methylation 450 K BeadChip and MethylationEPIC BeadChip. For each diet score, we performed linear EWAS adjusted for age, sex, blood cells, smoking and technical variables, and BMI in a second set of models. We also conducted Mendelian randomization analyses to assess the potential causal relationship between diet-related CpGs and cardiometabolic traits. RESULTS: We found 18 differentially methylated CpGs associated with dietary scores (p-value < 1.08 × 10-7; Bonferroni correction), of which 12 were previously associated with cardiometabolic traits. Enrichment analysis revealed overrepresentation of diet-associated genes in pathways involved in inflammation and cardiovascular disease. Mendelian randomization analyses suggested that genetically determined methylation levels corresponding to lower diet quality at cg02079413 (SNORA54), cg02107842 (MAST4), and cg23761815 (SLC29A3) were causally associated with higher BMI, and at cg05399785 (WDR8) with greater SBP; and methylation levels associated with higher diet quality at cg00711496 (PRMT1) with lower BMI, T2D risk and CHD risk, and at cg0557921 (AHRR) with lower CHD risk. CONCLUSIONS: Diet quality in adults was related to differential methylation in blood at 18 CpGs, some of which related to cardiometabolic health.Availability: The R code for the analysis is available in the following Github repository: https://github.com/jorgedb98/B64_DIAMETR.git

Combined Body Mass Index and Waist-To-Height Ratio and Its Association With Lifestyle and Health Factors Among Spanish Children: The PASOS Study

[Abstract] Background and Aims: The World Health Organization recommended simultaneous measurement of body mass index (BMI) and waist circumference (WC) and suggested joint use to predict disease risks. The aim of this study was to assess the prevalence of BMI and waist-toheight ratio (WHtR) categories among Spanish children and adolescents, as well as their associations with several lifestyle factors. Methods: Cross-sectional analysis of 8–16-year-old children and adolescents (n = 3772) were included in the PASOS nationwide representative study. Children/adolescents and their mothers/female caregivers answered a questionnaire on lifestyle and health factors. Child/adolescent anthropometrics were measured. Four combined BMI-WHtR disease risk categories were built. Results: A third of participants showed combined BMI-WHtR categories with high disease risk (12.3% ‘increased risk’, 9.7% ‘high risk’, 14.3% ‘very high risk’). Participants in the ‘very high risk’ group were less likely to be females (odds ratio 0.63; 95% CI: 0.52–0.76) and adolescents (0.60; 95% CI: 0.49–0.72), to practice _60 min/day of moderate-vigorous physical activity (MVPA) (0.73; 95% CI: 0.57–0.93), and to watch <120 min/day of total screen time on weekdays (0.61; 95% CI: 0.49–0.76). Mothers of participants in the ‘very high risk’ group were less likely to have a high educational level, be in the overweight or normal range, have never smoked or were former smokers, and watch <120 min/day of total screen time on weekends. Participants in the ‘increased’ and ‘high risk’ categories had mothers with normal weight and _60 min/day of MVPA. Participants in the ’high risk’ group did not achieve _60 min/day of MVPA and showed lower adherence to the Mediterranean diet. Conclusions: Adherence to a healthy lifestyle in children and adolescents, but also in their mothers/female caregivers during offspring’s childhood and adolescence, is associated with low BMI-WHtR disease risk

Determinants of adherence to the Mediterranean diet in Spanish children and adolescents: the PASOS study

[Abstract]: A progressive shift away from traditional healthy dietary patterns, such as the Mediterranean diet (MedDiet), has been observed in recent decades. The aim of this study was to assess determinants of optimal adherence to the MedDiet in Spanish children and adolescents. A cross-sec-tional analysis was included in the PASOS nationwide representative study in Spain. Participants were 3607 children and adolescents; 8–16 years old. Primary and secondary outcome measures of weight and height were measured. Adherence to the MedDiet, physical activity, and sedentary behavior in children and adolescents, as well as parental physical activity and dietary habits, were assessed. Optimal adherence to the MedDiet was observed in 45.5% of primary school students and 34.8% of secondary school students (OR: 0.65; 95%CI: 0.56–0.75). Optimal adherence to the MedDiet was higher in children/adolescents meeting daily recommended moderate and vigorous physical activity (OR: 2.39, 95%CI: 1.97–2.89) and in those meeting daily recommended screen time on week-days (OR: 2.05, 95%CI: 1.77–2.38) and weekends (OR: 1.76, 95%CI: 1.48–2.10). Participants with optimal adherence to the MedDiet were more likely to have mothers with a high-level education and high-tercile of SDQS, mothers who never smoked or were former smokers, and mothers who met the recommended physical activity and screen time. It can be concluded that a low prevalence of optimal adherence to the MedDiet was found among current Spanish children and adolescents. Optimal adherence to the MedDiet was associated with reaching the recommendations on physical activity and screen time, with the highest maternal educational level, and healthier maternal life-style

Determinants of adherence to the mediterranean diet in Spanish children and adolescents: the PASOS Study

A progressive shift away from traditional healthy dietary patterns, such as the Mediterranean diet (MedDiet), has been observed in recent decades. The aim of this study was to assess determinants of optimal adherence to the MedDiet in Spanish children and adolescents. A cross-sectional analysis was included in the PASOS nationwide representative study in Spain. Participants were 3607 children and adolescents; 8–16 years old. Primary and secondary outcome measures of weight and height were measured. Adherence to the MedDiet, physical activity, and sedentary behavior in children and adolescents, as well as parental physical activity and dietary habits, were assessed. Optimal adherence to the MedDiet was observed in 45.5% of primary school students and 34.8% of secondary school students (OR: 0.65; 95%CI: 0.56–0.75). Optimal adherence to the MedDiet was higher in children/adolescents meeting daily recommended moderate and vigorous physical activity (OR: 2.39, 95%CI: 1.97–2.89) and in those meeting daily recommended screen time on week-days (OR: 2.05, 95%CI: 1.77–2.38) and weekends (OR: 1.76, 95%CI: 1.48–2.10). Participants with optimal adherence to the MedDiet were more likely to have mothers with a high-level education and high-tercile of SDQS, mothers who never smoked or were former smokers, and mothers who met the recommended physical activity and screen time. It can be concluded that a low prevalence of optimal adherence to the MedDiet was found among current Spanish children and adolescents. Optimal adherence to the MedDiet was associated with reaching the recommendations on physical activity and screen time, with the highest maternal educational level, and healthier maternal life-styles.The PASOS study was funded by Fundación PROBITAS and the Gasol Foundation. Additional funds were received from the Barça Foundation, Banco Santander, IFA, Vienna and the Fundación Deporte Joven (no references are applicable). J.A.T., C.B., M.M.G., and M.M.B. were funded by CIBEROBN (CB12/03/30038) of the Institute of Health Carlos III (ISCIII), and co-funded by the European Regional Development Fund

Consumption of aspartame and other artificial sweeteners and risk of cancer in the Spanish multicase‐control study (MCC‐Spain)

[EN] Use of artificial sweeteners (AS) such as aspartame, cyclamate, saccharin and sucralose is widespread. We evaluated the association of use of aspartame and other AS with cancer. In total 1881 colorectal, 1510 breast, 972 prostate and 351 stomach cancer and 109 chronic lymphocytic leukaemia (CLL) cases and 3629 population controls from the Spanish Multicase-Control (MCC-Spain) study were recruited (2008-2013). The consumption of AS, from table-top sweeteners and artificially sweetened beverages, was assessed through a self-administered and validated food frequency questionnaire (FFQ). Sex-specific quartiles among controls were determined to compare moderate consumers (<third quartile) and high consumers (≥ third quartile) vs non consumers (reference category), distinguishing aspartame-containing products and other AS. Unconditional logistic regression models were used to estimate adjusted OR and 95%CI, and results were stratified by diabetes status. Overall, we found no associations between the consumption of aspartame or other AS and cancer. Among participants with diabetes, high consumption of other AS was associated with colorectal cancer (OR = 1.58, 95% CI 1.05-2.41, P trend = .03) and stomach cancer (OR = 2.27 [0.99-5.44], P trend = .06). High consumption of aspartame, was associated with stomach cancer (OR = 2.04 [0.7-5.4], P trend = .05), while a lower risk was observed for breast cancer (OR = 0.28 [0.08-0.83], P trend = .03). In some cancers, the number of cases in participants with diabetes were small and results should be interpreted cautiously. We did not find associations between use of AS and cancer, but found associations between high consumption of aspartame and other AS and different cancer types among participants with diabetes.SIAGAURConsejería de Salud of the Junta de AndalucíaConsejería de Sanidad de la Región de MurciaConselleria de Sanitat of the Generalitat ValencianaFundaci on Caja de Ahorros de AsturiasFundación Marqués de ValdecillaGeneralitat de CatalunyaICGC International Cancer Genome Consortium CLLJunta de Castilla y Leó

Combined body mass index and waist-to-height ratio and its association with lifestyle and health factors among Spanish children: the PASOS study

Background and Aims: The World Health Organization recommended simultaneous measurement of body mass index (BMI) and waist circumference (WC) and suggested joint use to predict disease risks. The aim of this study was to assess the prevalence of BMI and waist-to-height ratio (WHtR) categories among Spanish children and adolescents, as well as their associations with several lifestyle factors. Methods: Cross-sectional analysis of 8–16-year-old children and adolescents (n = 3772) were included in the PASOS nationwide representative study. Children/adolescents and their mothers/female caregivers answered a questionnaire on lifestyle and health factors. Child/adolescent anthropometrics were measured. Four combined BMI-WHtR disease risk categories were built. Results: A third of participants showed combined BMI-WHtR categories with high disease risk (12.3% ‘increased risk’, 9.7% ‘high risk’, 14.3% ‘very high risk’). Participants in the ‘very high risk’ group were less likely to be females (odds ratio 0.63; 95% CI: 0.52–0.76) and adolescents (0.60; 95% CI: 0.49–0.72), to practice ≥60 min/day of moderate-vigorous physical activity (MVPA) (0.73; 95% CI: 0.57–0.93), and to watch <120 min/day of total screen time on weekdays (0.61; 95% CI: 0.49–0.76). Mothers of participants in the ‘very high risk’ group were less likely to have a high educational level, be in the overweight or normal range, have never smoked or were former smokers, and watch <120 min/day of total screen time on weekends. Participants in the ‘increased’ and ‘high risk’ categories had mothers with normal weight and ≥60 min/day of MVPA. Participants in the ’high risk’ group did not achieve ≥60 min/day of MVPA and showed lower adherence to the mediterranean diet. Conclusions: Adherence to a healthy lifestyle in children and adolescents, but also in their mothers/female caregivers during offspring’s childhood and adolescence, is associated with low BMI-WHtR disease risk.The PASOS study was funded by Fundación PROBITAS and the Gasol Foundation. Additional funds were received from the Barça Foundation, Banco Santander, IFA, Vienna and the Fundación Deporte Joven (no references are applicable). J.A.T., C.B., M.M.G., and M.d.M.B. were funded by CIBEROBN (CB12/03/30038) of the Institute of Health Carlos III (ISCIII), and co-funded by the European Regional Development Fund