Does consumption of ultra-processed foods matter for liver health? Prospective analysis among older adults with metabolic syndrome

Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of liver alterations that can result in severe disease and even death. Consumption of ultra-processed foods (UPF) has been associated with obesity and related comorbidities. However, the link between UPF and NAFLD has not been sufficiently assessed. We aimed to investigate the prospective association between UPF consumption and liver health biomarkers. Methods: We followed for 1 year 5867 older participants with overweight/obesity and metabolic syndrome (MetS) from the PREDIMED-Plus trial. A validated 143-item semi-quantitative food frequency questionnaire was used to evaluate consumption of UPF at baseline, 6, and 12 months. The degree of processing for foods and beverages (g/day) was established according to the NOVA classification system. The non-invasive fatty liver index (FLI) and hepatic steatosis index (HSI) were used to evaluate liver health at three points in time. The associations between changes in UPF consumption (percentage of total daily dietary intake (g)) and liver biomarkers were assessed using mixed-effects linear models with repeated measurements. Results: In this cohort, UPF consumption at baseline was 8.19% (SD 6.95%) of total daily dietary intake in grams. In multivariable models, each 10% daily increment in UPF consumption in 1 year was associated with significantly greater FLI (β 1.60 points, 95% CI 1.24;1.96 points) and HSI (0.43, 0.29; 0.57) scores (all p-values < 0.001). These associations persisted statistically significant after adjusting for potential dietary confounders and NAFLD risk factors. Conclusions: A higher UPF consumption was associated with higher levels of NAFLD-related biomarkers in older adults with overweight/obesity and MetS.This work was supported by the European Research Council (Advanced Research Grant 2014–2019; agreement #340918) granted to MÁM-G and the Spanish National Health Institute of Health Carlos III (ISCIII), through CIBEROBN and “Fondo de Investigación para la Salud” (FIS), which is co-funded by the European Regional Development Fund (six coordinated FIS projects led by JS-S and JVi, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332, PI20/01802, PI20/00138, PI20/01532, PI20/00456, PI20/00339, PI20/00557, PI20/00886, PI20/01158, PI21/00465); the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to JS-S; the Recercaixa (number 2013ACUP00194) grant to JS-S; grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, PI0137/2018, RH-0024-2021); the PROMETEO/2017/017 grant from the Generalitat Valenciana; and the SEMERGEN grant; Juan de la Cierva-Incorporación research grant (IJC2019-042420-I) of the Spanish Ministry of Economy, Industry and Competitiveness and European Social Funds to JK; Miguel Servet Tipo 2 research grant (CPII20/00014) of the Spanish National Health Institute of Health Carlos III (ISCIII) to MRBL This work was also partially supported by ICREA under the ICREA Academia programme. None of the funding sources took part in the design, collection, analysis, interpretation of the data, or writing the report, or in the decision to submit the manuscript for publication

Effect of mistimed eating patterns on breast and prostate cancer risk (MCC-Spain Study)

Modern life involves mistimed sleeping and eating patterns that in experimental studies are associated with adverse health effects. We assessed whether timing of meals is associated with breast and prostate cancer risk taking into account lifestyle and chronotype, a characteristic correlating with preference for morning or evening activity. We conducted a population-based case-control study in Spain, 2008-2013. In this analysis we included 621 cases of prostate and 1,205 of breast cancer and 872 male and 1,321 female population controls who had never worked night shift. Subjects were interviewed on timing of meals, sleep and chronotype and completed a Food Frequency Questionaire. Adherence to the World Cancer Research Fund/American Institute of Cancer Research recommendations for cancer prevention was examined. Compared with subjects sleeping immediately after supper, those sleeping two or more hours after supper had a 20% reduction in cancer risk for breast and prostate cancer combined (adjusted Odds Ratio [OR] = 0.80, 95%CI 0.67-0.96) and in each cancer individually (prostate cancer OR = 0.74, 0.55-0.99; breast cancer OR = 0.84, 0.67-1.06). A similar protection was observed in subjects having supper before 9 pm compared with supper after 10 pm. The effect of longer supper-sleep interval was more pronounced among subjects adhering to cancer prevention recommendations (OR both cancers= 0.65, 0.44-0.97) and in morning types (OR both cancers = 0.66, 0.49-0.90). Adherence to diurnal eating patterns and specifically a long interval between last meal and sleep are associated with a lower cancer risk, stressing the importance of evaluating timing in studies on diet and cancer

Consumption of ultra-processed foods and drinks and colorectal, breast, and prostate cancer

Aims: To study whether the consumption of ultra-processed foods and drinks is associated with breast, colorectal, and prostate cancers. Methods: Multicentric population-based case-control study (MCC-Spain) conducted in 12 Spanish provinces. Participants were men and women between 20 and 85 years of age with diagnoses of colorectal (n = 1852), breast (n = 1486), or prostate cancer (n = 953), and population-based controls (n = 3543) frequency-matched by age, sex, and region. Dietary intake was collected using a validated food frequency questionnaire. Foods and drinks were categorized according to their degree of processing based on the NOVA classification. Unconditional multivariable logistic regression was used to evaluate the association between ultra-processed food and drink consumption and colorectal, breast, and prostate cancer. Results: In multiple adjusted models, consumption of ultra-processed foods and drinks was associated with a higher risk of colorectal cancer (OR for a 10% increase in consumption: 1.11; 95% CI 1.04-1.18). The corresponding odds for breast (OR 1.03; 95% CI 0.96-1.11) and prostate cancer (OR 1.02; 95% CI 0.93-1.12) were indicative of no association. Conclusions: Results of this large population-based case-control study suggest an association between the consumption of ultra-processed foods and drinks and colorectal cancer. Food policy and public health should include a focus on food processing when formulating dietary guidelines

Dietary inflammatory index, dietary non-enzymatic antioxidant capacity, and colorectal and breast cancer risk (MCC-Spain Study)

Inflammation and antioxidant capacity have been associated with colorectal and breast cancer. We computed the dietary inflammatory index (DII®), and the total dietary non-enzymatic antioxidant capacity (NEAC) and associated them with colorectal and breast cancer risk in the population-based multi case-control study in Spain (MCC-Spain). We included 1852 colorectal cancer and 1567 breast cancer cases, and 3447 and 1486 population controls, respectively. DII score and NEAC were derived using data from a semi-quantitative validated food frequency questionnaire. Unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95%CI) for energy-adjusted DII (E-DII), and a score combining E-DII and NEAC. E-DII was associated with colorectal cancer risk (OR = 1.93, highest quartile versus lowest, 95%CI:1.60-2.32; p-trend: 0.10). The combined score of high E-DII scores and low antioxidant values were associated with colorectal cancer risk (OR = 1.48, highest quartile versus lowest, 95%CI: 1.26-1.74; p-trend: <0.001), but not breast cancer. This study provides evidence that a pro-inflammatory diet is associated with increased colorectal cancer risk while findings for breast cancer were less consistent

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

Maternal diet during pregnancy and micronuclei frequency in peripheral blood T lymphocytes in mothers and newborns (Rhea cohort, Crete)

Purpose: The study assessed whether diet and adherence to cancer prevention guidelines during pregnancy were associated with micronucleus (MN) frequency in mothers and newborns. MN is biomarkers of early genetic effects that have been associated with cancer risk in adults. Methods: A total of 188 mothers and 200 newborns from the Rhea cohort (Greece) were included in the study. At early-mid pregnancy, we conducted personal interviews and a validated food frequency questionnaire was completed. With this information, we constructed a score reflecting adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention guidelines on diet, physical activity and body fatness. At delivery, maternal and/or cord blood was collected to measure DNA and hemoglobin adducts of dietary origin and frequencies of MN in binucleated and mononucleated T lymphocytes (MNBN and MNMONO). Results: In mothers, higher levels of red meat consumption were associated with increased MNBN frequency [2nd tertile IRR = 1.34 (1.00, 1.80), 3rd tertile IRR = 1.33 (0.96, 1.85)] and MNMONO frequency [2nd tertile IRR = 1.53 (0.84, 2.77), 3rd tertile IRR = 2.69 (1.44, 5.05)]. The opposite trend was observed for MNBN in newborns [2nd tertile IRR = 0.64 (0.44, 0.94), 3rd tertile IRR = 0.68 (0.46, 1.01)], and no association was observed with MNMONO. Increased MN frequency in pregnant women with high red meat consumption is consistent with previous knowledge. Conclusions: Our results also suggest exposure to genotoxics during pregnancy might affect differently mothers and newborns. The predictive value of MN as biomarker for childhood cancer, rather than adulthood, remains unclear. With few exceptions, the association between maternal carcinogenic exposures during pregnancy and childhood cancer or early biologic effect biomarkers remains poorly understood.The Rhea cohort was funded by the following European projects NewGeneris (FP-6-FOOD-CT-2005-016320), ESCAPE (FP7-2007-211250), HiWATE (FP-6-FOOD-CT-2006-036224), Envirogenomarkers (FP7-2008-ENV-1.2.1.4), CHICOS (FP7-2009-GA 241604), and ENRIECO (FP7-2008-GA 226285). COG holds a Sara Borrell postdoctoral fellowship awarded from the Carlos III National Institute of Health (CD13/00072). MP held a Juan de la Cierva postdoctoral fellowship awarded from the Spanish Ministry of Ministry of Economy and Competitiveness (JCI-2011-09479). DFM received support from the Italian Ministry of Health, 5x1000 Grant-2011

Association of time of breakfast and nighttime fasting duration with breast cancer risk in the multicase-control study in Spain

Circadian nutritional behaviors, defined by the daily eating/fasting cycle, have been linked with breast cancer. This study aimed to further disentangle the association of nighttime fasting duration and time of breakfast with breast cancer risk. We analyzed data from 1,181 breast cancer cases and 1,326 population controls from the Spanish multicase-control study (MCC-Spain), 2008-2013. We collected circadian nutritional behaviors at mid-age via a telephonic interview. We applied logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of nighttime fasting duration and time of breakfast with breast cancer risk in all women and stratified by menopausal status. Models were adjusted for age, center, education, family history of breast cancer, age at menarche, number of children, breastfeeding, age at first child, body mass index (BMI), contraceptive use, and hormonal replacement therapy (HRT). A later time of breakfast was associated with a non-significant increased risk of breast cancer (OR = 1.05, 95% CI: 0.95-1.16, per hour increase). This association was stronger among premenopausal women, among whom each hour later, the time of breakfast was associated with an 18% increase in breast cancer risk (OR = 1.18, 95% CI: 1.01-1.40). The association was not observed in postmenopausal women. We did not observe an association between nighttime fasting duration and breast cancer risk after adjusting for the time of breakfast. In this study, late breakfast was associated with increased breast cancer risk, especially among premenopausal women, compared with early breakfast. Aside from nutritional quality, circadian nutritional behaviors should be further studied in relation to cancer.This study was partially funded by the “Accion Transversal del Cancer,” approved on the Spanish Ministry Council on the 11 October 2007, Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01889, PI11/02213, PI12/00488, PI12/01270, PI12/00715, PI14/01219, PI14/0613, and PI17/01388), Fundación Marqués de Valdecilla (API 10/09), the ICGC International Cancer Genome Consortium CLL [The ICGC CLL-Genome Project was 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)], the Junta de Castilla y León (LE22A10-2), the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, and salud201200057018tra), the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), the Recercaixa (2010ACUP 00310), the Regional Government of the Basque Country, the Consejería de Sanidad de la Región de Murcia, by the European Commission grants FOOD-CT-2006-036224-HIWATE, the Spanish Association Against Cancer (AECC) Scientific Foundation, by the Catalan Government—Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723 and 2014SGR850, the Fundación Caja de Ahorros de Asturias, and 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. AP-C was supported by the MINECO (Ministry of Economy in Spain) Grant no. PRE2019-089038, fellowship

Prenatal Phthalate Exposure and Childhood Growth and Blood Pressure: Evidence from the Spanish INMA-Sabadell Birth Cohort Study

BACKGROUND: Human evidence on the effects of early life phthalate exposure on obesity and cardiovascular disease risks, reported by experimental studies, is limited to a few cross-sectional studies. OBJECTIVES: We evaluated the associations between prenatal phthalate exposure and childhood growth and blood pressure in a Spanish birth cohort study. METHODS: We assessed exposure using the average of two phthalate metabolite spot-urine concentrations collected from the mothers in the first and third pregnancy trimesters (creatinine-adjusted, n = 391). Study outcomes were the difference in age- and sex-specific z-scores for weight between birth and 6 months of age; and repeated age- and sex-specific z-scores for body mass index (BMI) at 1, 4, and 7 years; waist-to-height ratio at 4 and 7 years; and age- and height-specific z-scores for systolic and diastolic blood pressure at 4 and 7 years. RESULTS: The sum of five high-molecular-weight phthalate metabolites (ΣHMWPm) was associated with lower weight z-score difference between birth and 6 months (β per doubling of exposure = -0.41; 95% CI: -0.75, -0.06) and BMI z-scores at later ages in boys (β = -0.28; 95% CI: -0.60, 0.03) and with higher weight z-score difference (β = 0.24; 95% CI: -0.16, 0.65) and BMI z-scores in girls (β = 0.30; 95% CI: -0.04, 0.64) (p for sex interaction = 0.01 and 0.05, respectively). The sum of three low-molecular-weight phthalates (ΣLMWPm) was not significantly associated with any of the growth outcomes. ΣHMWPm and ΣLMWPm were associated with lower systolic blood pressure z-scores in girls but not in boys. CONCLUSIONS: This study suggests that prenatal phthalate exposure may be associated with postnatal growth and blood pressure in a sex-specific manner. Inconsistencies with previous cross-sectional findings highlight the necessity for evaluating phthalate health effects in prospective studies.This study was funded by grants from the RecerCaixa (Register no. 2010ACUP00349), the “Instituto Carlos III” (Red INMA G03/176, CB06/02/0041 and predoctoral grant PFIS 2010, Register no. FI10/00399), the Spanish Ministry of Health (FIS-PI041436, FIS-PI081151), the Generalitat de Catalunya-CIRIT (1999SGR 00241), and the Fundació Roger Torn

Neighbourhood walkability and physical activity: moderating role of a physical activity intervention in overweight and obese older adults with metabolic syndrome

Background: While urban built environments might promote active ageing, an infrequently studied question is how the neighbourhood walkability modulates physical activity changes during a physical activity intervention programme in older adults. We assessed the influence of objectively assessed neighbourhood walkability on the change in physical activity during the intervention programme used in the ongoing PREvención con DIeta MEDiterránea (PREDIMED)-Plus trial. Method: The present study involved 228 PREDIMED-Plus senior participants aged between 55 and 75, recruited in Palma de Mallorca (Spain). Overweight/obese older adults with metabolic syndrome were randomised to an intensive weight-loss lifestyle intervention or a control group. A walkability index (residential density, land use mix, intersections density) was calculated using geographic information systems (1 km sausage-network buffer). Physical activity was assessed using accelerometer and a validated questionnaire, at baseline and two follow-up visits (6-months and 1-year later). Generalised additive mixed models were fitted to estimate the association between the neighbourhood walkability index and changes in physical activity during follow-up. Results: Higher neighbourhood walkability (1 z-score increment) was associated with moderate-to-vigorous accelerometer assessed physical activity duration, (β = 3.44; 95% CI = 0.52; 6.36 min/day). When analyses were stratified by intervention arm, the association was only observed in the intervention group (β = 6.357; 95% CI = 2.07;10.64 min/day) (P for interaction = 0.055). Conclusions: The results indicate that the walkability of the neighbourhood could support a physical activity intervention, helping to maintain or increase older adults' physical activity