Olive oil consumption is associated with lower cancer, cardiovascular and all-cause mortality among Italian adults: prospective results from the Moli-sani Study and analysis of potential biological mechanisms.

BACKGROUND: Olive oil consumption has been reportedly associated with lower mortality rates, mostly from cardiovascular diseases, but its potential impact on cancer death remains controversial. Moreover, biological mechanisms possibly linking olive oil consumption to mortality outcomes remain unexplored. METHODS: We longitudinally analysed data on 22,892 men and women from the Moli-sani Study in Italy (follow-up 13.1 y), to examine the association of olive oil consumption with mortality. Dietary data were collected at baseline (2005-2010) through a 188-item FFQ, and olive oil consumption was standardised to a 10 g tablespoon (tbsp) size. Diet quality was assessed through a Mediterranean diet score. Multivariable-adjusted Cox proportional hazard models, also including diet quality, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The potential mediating role of inflammatory, metabolic, cardiovascular and renal biomarkers on the association between olive oil intake and mortality was evaluated on the basis of change-in-estimate and associated p values. RESULTS: Multivariable HRs for all-cause, cancer, cardiovascular and other cause mortality associated with high (>3 tbsp/d) versus low (≤1.5 tbsp/d) olive oil consumption were 0.80 (0.69-0.94), 0.77 (0.59-0.99), 0.75 (0.58-0.97) and 0.97 (0.73-1.29), respectively. Taken together, the investigated biomarkers attenuated the association of olive oil consumption with all-cause and cancer mortality by 21.2% and 13.7%, respectively. CONCLUSIONS: Higher olive oil consumption was associated with lower cancer, cardiovascular and all-cause mortality rates, independent of overall diet quality. Known risk factors for chronic diseases only in part mediated such associations suggesting that other biological pathways are potentially involved in this relationship.

Identifying brain tumor patients' subtypes based on pre-diagnostic history and clinical characteristics: a pilot hierarchical clustering and association analysis.

Introduction: Central nervous system (CNS) tumors are severe health conditions with increasing incidence in the last years. Different biological, environmental and clinical factors are thought to have an important role in their epidemiology, which however remains unclear. Objective: The aim of this pilot study was to identify CNS tumor patients' subtypes based on this information and to test associations with tumor malignancy. Methods: 90 patients with suspected diagnosis of CNS tumor were recruited by the Neurosurgery Unit of IRCCS Neuromed. Patients underwent anamnestic and clinical assessment, to ascertain known or suspected risk factors including lifestyle, socioeconomic, clinical and psychometric characteristics. We applied a hierarchical clustering analysis to these exposures to identify potential groups of patients with a similar risk pattern and tested whether these clusters associated with brain tumor malignancy. Results: Out of 67 patients with a confirmed CNS tumor diagnosis, we identified 28 non-malignant and 39 malignant tumor cases. These subtypes showed significant differences in terms of gender (with men more frequently presenting a diagnosis of cancer; p = 6.0 ×10-3) and yearly household income (with non-malignant tumor patients more frequently earning ≥25k Euros/year; p = 3.4×10-3). Cluster analysis revealed the presence of two clusters of patients: one (N=41) with more professionally active, educated, wealthier and healthier patients, and the other one with mostly retired and less healthy men, with a higher frequency of smokers, personal history of cardiovascular disease and cancer familiarity, a mostly sedentary lifestyle and generally lower income, education and cognitive performance. The former cluster showed a protective association with the malignancy of the disease, with a 74 (14-93) % reduction in the prevalent risk of CNS malignant tumors, compared to the other cluster (p=0.026). Discussion: These preliminary data suggest that patients' profiling through unsupervised machine learning approaches may somehow help predicting the risk of being affected by a malignant form. If confirmed by further analyses in larger independent cohorts, these findings may be useful to create potential intelligent ranking systems for treatment priority, overcoming the lack of histopathological information and molecular diagnosis of the tumor, which are typically not available until the time of surgery.

Food processing and risk of central nervous system tumours: A preliminary case-control analysis from the MEditerranean DIet in relation to CancEr of brAin (MEDICEA) study.

BACKGROUND: The relationship between diet and central nervous system (CNS) tumours was almost exclusively focused on food composition. We evaluated the relationship of different degrees of food processing with risk of CNS tumours. METHODS: The study sample included 44 CNS tumours cases (20 non-malignant and 24 malignant) recruited from the Neurosurgery Department at the IRCCS Neuromed (Italy), and 88 controls matched 1:2 for sex and age± 10 years, identified from the Moli-sani Study. Dietary intake was assessed using a 188-item FFQ. Food items were grouped according to the NOVA classification on the basis of processing as: (1) unprocessed/minimally processed foods; (2) processed culinary ingredients; (3) processed foods; and (4) ultra-processed food (UPF). Conditional logistic regression models were used to estimate odds ratio (OR) and 95% confidence intervals (95%CI) of dietary contributions from each NOVA group (as weight ratio on the total food eaten) and adjusting for potential confounders. RESULTS: In a multivariable conditional to match logistic regression analysis also controlled for overall diet quality, 1% increment in UPF intake was associated with higher odds of all CNS tumours (OR = 1.06; 1.01-1.13), particularly of malignant CNS tumours (OR = 1.11; 1.02-1.22), while no association with non-malignant CNS tumours was found (OR = 1.06; 0.99-1.15). In contrast, only processed food was inversely associated with risk of both CNS tumours overall (OR = 0.94; 0.90-0.98) and of malignant CNS tumours (OR = 0.90; 0.83-0.96). CONCLUSION: Increasing UPF intake was associated with higher risk of CNS tumours, especially malignant ones, independently of the overall diet quality, while only processed food (but not UPF) was inversely related to the risk of this disease.

The Dietary Intake of Polyphenols Is Associated with a Lower Risk of Severe Lumbar Spinal Stenosis: A Case-Control Analysis from the PREFACE Study.

Polyphenols are naturally occurring compounds endowed with antioxidant and anti-inflammatory properties. We sought to examine the association of dietary polyphenols with the risk of severe lumbar spinal stenosis (LSS), a condition possibly characterized by a high inflammatory component. A case-control study included 156 patients with LSS and indication to surgery and 312 controls, matched (1:2) for sex, age (±6 months), and physical activity. The polyphenol intake was calculated by matching food consumption data from a 188-item food frequency questionnaire with the Phenol-Explorer database regarding the polyphenol content of each reported food. In a multivariable-adjusted logistic regression analysis including lifestyles, sociodemographic factors, and the Mediterranean Diet Score, a 1-standard deviation (SD) increase in dietary polyphenols intake was associated with lower odds of LSS (Odds ratio [OR] = 0.65; 95% CI: 0.47-0.89). Analyses of different polyphenol classes showed that a per 1-SD in the consumption of flavonoids and stilbenes was related to lower LSS risk (OR = 0.57; 95% CI: 0.42-0.78; OR = 0.40; 95% CI: 0.27-0.61, respectively). Further adjustment for the total dietary antioxidant capacity did not modify the strength of these associations. A diet rich in polyphenols is independently associated with a lower risk of severe LSS, possibly through mechanisms that include the anti-inflammatory potential of these bioactive compounds.

Incremental monounsaturated to saturated fat ratio and fibre consumption is associated with a reduction in a composite score of modifiable cardiovascular risk factors: Prospective results from the Moli-sani study.

BACKGROUND/OBJECTIVES: Unsaturated fats, fibre-rich foods and polyphenols are distinctive features of a traditional Mediterranean diet and have pleiotropic properties possibly contributing to reduce the long-term risk of non-communicable diseases and mortality associated with this diet. We aimed to evaluate whether changes over time in dietary fats, fibre and polyphenols consumption are associated with modifications in cardiovascular disease (CVD) risk factors. METHODS: The analytic sample consists of a sub-cohort of 2023 men and women enrolled in the Moli-sani Study (n = 24,325). Dietary and health data were obtained both at baseline (2005-2010) and at re-examination (2017-2020). The exposures were changes in dietary fats, fibre and polyphenols consumption measured after 12.7 years (median), and the outcome was change in a composite score including 13 modifiable CVD risk factors (e.g., blood lipids, C-reactive protein), measured both at enrolment and after the 12.7 years period. RESULTS: In multivariable-adjusted analysis including lifestyles, sociodemographic and clinical factors, an incremental intake of the ratio of monounsaturated to saturated fats or of fibre was associated with a reduction in the composite score of CVD risk factors (ß = -0.086; 95%CI -0.150, -0.021 and ß = -0.051; 95%CI -0.091, -0.012, respectively). Change in polyphenol intake was not associated with a substantial variation in the CVD risk score (p = 0.15). CONCLUSIONS: An incremental consumption over time of monounsaturated versus saturated fats and of fibre was associated with an improvement in modifiable CVD risk factors as reflected by a composite score.

Mediterranean diet and other dietary patterns in association with biological aging in the Moli-sani Study cohort.

BACKGROUND & AIMS: Biological age (BA) is the hypothetical underlying age of an organism and has been proposed as a more powerful predictor of health than chronological age (CA). The difference between BA and CA (Δage) reflects the rate of biological aging, with lower values indicating slowed-down aging. We sought to compare the relationship of four a priori-defined dietary patterns, including a traditional Mediterranean diet (MD) and three non-Mediterranean diets, with biological aging (Δage) among Italian adults. We also examined distinctive nutritional traits of these diets as potential mediators of such associations. METHODS: Cross-sectional analysis on a sub-cohort of 4510 subjects (aged ≥35 y; 52.0% women) from the Moli-sani Study (enrolment, 2005-2010). Food intake was recorded by a 188-item semi-quantitative food-frequency questionnaire. A Mediterranean diet score (MDS) was used as exposure and compared with non-Mediterranean dietary patterns, i.e. DASH (Dietary Approaches to Stop Hypertension), Palaeolithic and the Nordic diets. A Deep Neural Network based on 36 blood biomarkers was used to compute BA and the resulting Δage (BA-CA), which was tested as outcome in multivariable linear regressions adjusted for clinical factors, lifestyles and sociodemographic factors. RESULTS: In a multivariable-adjusted model, 1 standard deviation increase in the MDS was inversely associated with Δage (ß = -0.23; 95%CI -0.40, -0.07), and similar findings were observed with the DASH diet (ß = -0.17; 95%CI -0.33, -0.01). High dietary polyphenol content explained 29.8% (p = 0.04) and 65.8% (p = 0.02) of these associations, respectively, while other nutritional factors analysed (e.g. dietary fibre) were unlikely to be on the pathway. No significant associations were found with either the Palaeolithic or the Nordic diets. CONCLUSIONS: Increasing adherence to either the traditional MD or the DASH diet was associated with delayed biological aging, possibly through their high polyphenol content.

Dietary Polyphenol Intake Is Associated with Biological Aging, a Novel Predictor of Cardiovascular Disease: Cross-Sectional Findings from the Moli-Sani Study.

Biological aging, or the discrepancy between biological and chronological age of a subject (Δage), has been associated with a polyphenol-rich Mediterranean diet and represents a new, robust indicator of cardiovascular disease risk. We aimed to disentangle the relationship of dietary polyphenols and total antioxidant capacity with Δage in a cohort of Italians. A cross-sectional analysis was performed on a sub-cohort of 4592 subjects (aged ≥ 35 y; 51.8% women) from the Moli-sani Study (2005-2010). Food intake was recorded by a 188-item food-frequency questionnaire. The polyphenol antioxidant content (PAC)-score was constructed to assess the total dietary content of polyphenols. Total antioxidant capacity was measured in foods by these assays: trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP) and ferric reducing-antioxidant power (FRAP). A deep neural network, based on 36 circulating biomarkers, was used to compute biological age and the resulting Δage, which was tested as outcome in multivariable-adjusted linear regressions. Δage was inversely associated with the PAC-score (ß = -0.31; 95%CI -0.39, -0.24) but not with total antioxidant capacity of the diet. A diet rich in polyphenols, by positively contributing to deceleration of the biological aging process, may exert beneficial effects on the long-term risk of cardiovascular disease and possibly of bone health.

Changes in the consumption of foods characterising the Mediterranean dietary pattern and major correlates during the COVID-19 confinement in Italy: results from two cohort studies.

We investigated the effect of confinement during the COVID-19 pandemic on the consumption of foods characterising the Mediterranean dietary pattern (MDP) and its major correlates in two Italian population-based cohorts comprising 3161 subjects (mean age 57.7 ± 15.4 y). At population level, 38.8% of participants reported an improvement of diet quality during the first nationwide lockdown. Healthful dietary changes were associated with older age (ß = 0.41; 95% confidence interval [CI] 0.08, 0.73 for 56-65 vs. 18-39 y), greater wealth (ß = 0.45; 0.01, 0.89 for >40,000 ≤ 60,000 vs. ≤ 10,000 EUR/y), increased physical activity (ß = 0.52; 0.22, 0.81) and reduced body weight (ß = 0.36; 0.11, 0.62). Switching to healthy eating was also related to increased consumption of organic (ß = 1.24; 0.88, 1.60) and locally-grown food (ß = 0.74; 0.51, 0.96). The first Italian lockdown led, in a substantial part of the population, to higher intake of foods characterising a MDP; this was also accompanied by healthier lifestyle and more sustainable food choices.

Egg consumption and risk of all-cause and cause-specific mortality in an Italian adult population.

PURPOSE: Dietary guidelines recommend to limit egg consumption to 4 servings per week but the relation between egg intake and health outcomes is still controversial. To evaluate the association of egg consumption and mortality risk in Italian adults and to investigate nutritional factors and serum lipids as potentially explaining such associations. METHODS: Longitudinal analysis on 20,562 men and women aged ≥ 35y, free from cardiovascular disease (CVD) and cancer belonging to the Moli-sani Study cohort (enrolled 2005-2010) followed up for a median of 8.2 years. RESULTS: In multivariable-adjusted analysis as compared to low intake (> 0 ≤ 1 egg/week), eating > 4 eggs/week led to an increased risk of all-cause (Hazard ratio [HR] = 1.50; 95%CI 1.13-1.99), CVD (HR = 1.75; 1.07-2.87) and cancer mortality (HR = 1.52; 0.99-2.33). Similarly, an intake of 2-4 eggs/week was associated with higher all-cause (HR = 1.22; 1.01-1.46) and CVD mortality risk (HR = 1.43; 1.03-1.97). An increase of 1 egg per week was associated with higher mortality risk among high-risk individuals, such as those with hypertension and hyperlipidaemia. Dietary cholesterol explained about 43.0% and 39.3% (p values < 0.0001) of the association of eggs with all-cause and CVD mortality, respectively, while serum lipids (e.g., total cholesterol) accounted for a small proportion of egg-mortality relation. CONCLUSIONS: Among Italian adults, high egg consumption leads to an increased risk of all-cause and CVD mortality, with the risk being evident even at the recommended intake of 2-4 eggs per week. A substantial part of this association was likely due to the egg contribution to dietary cholesterol. Our findings suggest limiting the consumption of eggs in the diet and these results should be considered in the development of dietary guidelines and updates.

Daily Coffee Drinking Is Associated with Lower Risks of Cardiovascular and Total Mortality in a General Italian Population: Results from the Moli-sani Study.

BACKGROUND: An inverse relationship between coffee intake and mortality has been observed in several population cohorts, but rarely within Mediterranean countries. Moreover, the biological pathways mediating such an association remain unclear. OBJECTIVES: We assessed the associations between coffee consumption and total and cause-specific mortality and examined the mediating roles of N-terminal pro B-type natriuretic peptide (NTproBNP), high-sensitivity Troponin I, blood glucose, lipid metabolism, and selected biomarkers of inflammation and renal function. METHODS: We longitudinally analyzed data on 20,487 men and women (35-94 years old at baseline) in the Moli-sani Study, a prospective cohort established in 2005-2010. Individuals were free from cardiovascular disease (CVD) and cancer and were followed-up for a median of 8.3 years. Dietary data were collected by a 188-item semi-quantitative FFQ. Coffee intake was standardized to a 30-mL Italian espresso cup size. HRs with 95% CIs were calculated by multivariable Cox regression. RESULTS: In comparison with no/rare coffee consumption (up to 1 cup/d), HRs for all-cause mortality across categories of coffee consumption (>1 to ≤2, >2 to ≤3, >3 to ≤4 and >4 cups/d) were 0.79 (95% CI, 0.65-0.95), 0.84 (95% CI, 0.69-1.03), 0.72 (95% CI, 0.57-0.92), and 0.85 (95% CI, 0.62-1.12), respectively. For CVD mortality, a nonlinear (P for non-linearity = 0.021) J-shaped association was found (magnitude of the relative reduction = 37%; nadir at 3-4 cups/d). Circulating levels of NTproBNP explained up to 26.4% of the association between coffee and all-cause mortality, while systolic blood pressure was likely to be on the pathway between coffee and CVD mortality, although to a lesser extent. CONCLUSIONS: In this large cohort of Italian adults, moderate consumption (3-4 cups/d) of Italian-style coffee was associated with lower risks of all-cause and, specifically, of CVD mortality. Among the known biomarkers investigated here, NTproBNP likely mediates the relationship between coffee intake and all-cause mortality.

Chili Pepper Consumption and Mortality in Italian Adults.

BACKGROUND: Chili pepper is a usual part of a traditional Mediterranean diet. Yet epidemiological data on the association between chili pepper intake and mortality risk are scarce, with a lack of studies from Mediterranean populations. OBJECTIVES: This study sought to examine the association between chili pepper consumption and risk of death in a large sample of the adult Italian general population, and to account for biological mediators of the association. METHODS: Longitudinal analysis was performed on 22,811 men and women enrolled in the Moli-sani Study cohort (2005 to 2010). Chili pepper intake was estimated by the EPIC (European Prospective Investigation Into Cancer) Food Frequency Questionnaire and categorized as none/rare consumption, up to 2 times/week, >2 to ≤4 times/week, and >4 times/week. RESULTS: Over a median follow-up of 8.2 years, a total of 1,236 deaths were ascertained. Multivariable hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality among participants in the regular (>4 times/week) relative to none/rare intake were 0.77 (95% confidence interval [CI]: 0.66 to 0.90) and 0.66 (95% CI: 0.50 to 0.86), respectively. Regular intake was also inversely associated with ischemic heart disease (HR: 0.56; 95% CI: 0.35 to 0.87) and cerebrovascular (HR: 0.39; 95% CI: 0.20 to 0.75) death risks. The association of chili pepper consumption with total mortality appeared to be stronger in hypertension-free individuals (p for interaction = 0.021). Among known biomarkers of CVD, only serum vitamin D marginally accounted for such associations. CONCLUSIONS: In a large adult Mediterranean population, regular consumption of chili pepper is associated with a lower risk of total and CVD death independent of CVD risk factors or adherence to a Mediterranean diet. Known biomarkers of CVD risk only marginally mediate the association of chili pepper intake with mortality.

Association of proinflammatory diet with low-grade inflammation: results from the Moli-sani study.

OBJECTIVES: The association between diet and inflammation is well documented. Yet, no evidence exists on the relationship between the inflammatory potential of the diet and low-grade inflammation (LGI) as measured by a composite score of plasma and cellular biomarkers. The aim of this study was to assess the association between the Dietary Inflammatory Index (DII®) and LGI in a large population-based cohort. METHODS: Cross-sectional analyses were conducted on data from 20 823 adults (age ≥35 y; 48% male) without acute inflammation, who were recruited within the general population of the Moli-sani study from 2005 to 2010. LGI was measured by using a composite score (INFLA-score) including platelet and leukocyte counts, the granulocyte to lymphocyte ratio, and C-reactive protein. DII scores were computed based on dietary intake assessed by the EPIC food frequency questionnaire. Multivariable linear regression models were fit to produce adjusted regression coefficients and 95% confidence intervals (CIs). RESULTS: Higher DII scores were associated with increased LGI (ß = 0.131; 95% CI, 0.089-0.174 for the highest versus lowest quintile of DII) after adjusting for age, sex, lifestyle, prevalence of chronic diseases, and health conditions. A higher DII score also was positively associated with each single biomarker of inflammation included in the INFLA-score, unhealthy behaviors (smoking, sedentary lifestyle), and insulin. CONCLUSIONS: Higher DII scores, indicating greater inflammatory potential of the diet, were directly associated with LGI, as measured by a composite score of plasma and cellular biomarkers of inflammation. These findings are consistent with the contributing role of diet-mediated inflammation in increasing risk for inflammation-related chronic diseases.

Reduced mortality risk by a polyphenol-rich diet: An analysis from the Moli-sani study.

OBJECTIVES: The effect of the polyphenol content of the human diet on mortality risk is not yet fully understood. The aim of this study was to evaluate the association of a polyphenol-rich diet with mortality rate and a possible mediation effect by inflammation, in what we believe to be a novel, holistic approach. METHODS: We analyzed 21 302 participants (10 980 women and 10 322 men, aged ≥35 y) from the Moli-sani cohort. The participants were followed up for a median of 8.3 y. The European Prospective Investigation into Cancer and Nutrition food frequency questionnaire (FFQ) was used for dietary assessment. Flavonol, flavone, flavanone, flavanol, anthocyanin, isoflavone, and lignan intakes were calculated using European Food Information Resource-Bioactive Substances in Food Information Systems and the polyphenol antioxidant content (PAC)-score was constructed to assess the total content of these nutrients in the diet. RESULTS: Participants included in the highest quintile of intake of various polyphenol classes and subclasses presented a significant lower all-cause mortality risk compared with those in the lowest group of consumption (hazard ratio [HR] < 1; P <0.05). Cox regression analyses adjusted for potential confounders indicated that participants in higher quintiles of PAC-score had lower all-cause mortality risk (HR <1; P <0.05). When cause-specific mortality rates were considered, similar effects were observed for cardiocerebrovascular and cancer mortality (HR <1; P <0.05). CONCLUSIONS: The polyphenol content of the diet was associated with reduced mortality risk in a Mediterranean population, possibly through an antiinflammatory mechanism.