Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial

Background: Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk. Methods: We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models. Results: Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids). Conclusions: Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality. Clinical trial registration ISRCTN35739639

Dietary intake and major food sources of polyphenols in a Spanish population at high cardiovascular risk: The PREDIMED study

[Background and aims]: Epidemiological data have shown an inverse association between the consumption of polyphenol-rich foods and the risk of cardiovascular disease or overall mortality. A comprehensive estimation of individual polyphenol intake in nutritional cohorts is needed to gain a better understanding of this association. The aim of this study was to estimate the quantitative intake of polyphenols and the major dietary sources in the PREDIMED (PREvención con DIeta MEDiterránea) cohort using individual food consumption records. [Methods and results]: The PREDIMED study is a large, parallel-group, multicentre, randomised, controlled 5-year feeding trial aimed at assessing the effects of the Mediterranean diet on the primary prevention of cardiovascular disease. A total of 7200 participants, aged 55–80 years, completed a validated 1-year food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the recently developed Phenol-Explorer database on polyphenol content in foods. The mean total polyphenol intake was 820 ± 323 mg day−1 (443 ± 218 mg day−1 of flavonoids and 304 ± 156 mg day−1 of phenolic acids). Hydroxycinnamic acids were the phenolic group with the highest consumption and 5-caffeoylquinic acid was the most abundantly ingested individual polyphenol. The consumption of olives and olive oil was a differentiating factor in the phenolic profile of this Spanish population compared with other countries. [Conclusion]: In Mediterranean countries, such as Spain, the main dietary source of polyphenols is coffee and fruits, but the most important differentiating factor with respect to other countries is the consumption of polyphenols from olives and olive oil.The authors would like to express their gratitude for financial support from CICYT (AGL2009-13906-C02-02 and AGL2010-22319-C03), RETICS-RD06/0045, and PI11/02505 from the Spanish Ministry of Economy and Competitiveness (MEC) and ACOMP/2012/190 from the Generalitat Valenciana. The CIBERobn-CB06/03 is an initiative of the Instituto de Salud Carlos III, Spain. A.T-R would like to thank the ISCIII for granting her a predoctoral fellowship (FI10/00265) and J.P-J would like to thank the ISCIII for a Sara Borrell postdoctoral contract (CD09/00068)

Mediterranean Diet and atherothrombosis biomarkers: a randomized controlled trial

Scope. To assess whether following a Mediterranean diet (MedDiet) improved atherothrombosis biomarkers in high cardiovascular risk individuals. Methods and results. In 358 random volunteers from the PREvención con DIeta MEDiterránea trial, we assessed the 1-year effects on atherothrombosis markers of an intervention with MedDiet, enriched with virgin olive oil (MedDiet-VOO; n=120) or nuts (MedDiet-Nuts; n=119) versus a low-fat control diet (n=119). We also studied whether large increments in MedDiet adherence (≥3 score points, relative to compliance decreases) and intake changes in key food items were associated with 1-year differences in biomarkers. We observed differences between 1-year changes in the MedDiet-VOO intervention and control diet on the activity of platelet activating factor acetylhydrolase in HDLs (+7.5% [95% confidence interval: 0.17; 14.8]) and HDL-bound α1-antitrypsin levels (- 6.1% [-11.8; -0.29]), and between the MedDiet-Nuts intervention and the control arm on non-esterified fatty acid concentrations (-9.3% [-18.1; -0.53]). Large MedDiet adherence increments were associated with less fibrinogen (-9.5% [-18.3; -0.60]) and non-esterified fatty acid concentrations (-16.7% [-31.7; -1.74]). Increases in nut, fruit, vegetable, and fatty fish consumption, and decreases in processed meat intake were linked to beneficial changes in atherothrombosis biomarkers. Conclusion. Following a MedDiet improved atherothrombosis biomarkers in high cardiovascular risk individual

Glycemic index, glycemic load and invasive breast cancer incidence in postmenopausal women: The PREDIMED study

The objective of this study was to evaluate the prospective associations between dietary glycemic index (GI) and glycemic load (GL) and the risk for invasive breast cancer incidence in postmenopausal women at high cardiovascular disease (CVD) risk. This study was conducted within the framework of the PREvención con DIeta MEDiterránea (PREDIMED) study, a nutritional intervention trial for primary cardiovascular prevention. We included 4010 women aged between 60 and 80 years who were initially free from breast cancer but at high risk for CVD disease. Dietary information was collected using a validated 137-item food frequency questionnaire. We assigned GI values using the International Tables of GI and GL values. Cases were ascertained through yearly consultation of medical records and through consultation of the National Death Index. Only cases confirmed by results from cytology tests or histological evaluation were included. We estimated multivariable-adjusted hazard ratios for invasive breast cancer risk across tertiles of energy-adjusted dietary GI/GL using Cox regression models. We repeated our analyses using yearly repeated measures of GI/GL intakes. No associations were found between baseline dietary GI/GL and invasive breast cancer incidence. The multivariable hazard ratio and 95% confidence interval (CI) for the top tertile of dietary GI was 1.02 (95% CI: 0.42–2.46) and for dietary GL was 1.00 (95% CI: 0.44–2.30) when compared with the bottom tertile. Repeated-measures analyses yielded similar results. In sensitivity analyses, no significant associations were observed for women with obesity or diabetes. Dietary GI and GL did not appear to be associated with an increased risk for invasive breast cancer in postmenopausal women at high CVD risk

Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial

Background: Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk. Methods: We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models. Results: Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids). Conclusions: Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality. Clinical trial registration: ISRCTN35739639

A healthful plant-based diet is associated with lower type 2 diabetes risk via improved metabolic state and organ function: A prospective cohort study

BackgroundPlant-based diets are becoming increasingly popular due to favourable environmental footprints and have been associated with lower risk of type 2 diabetes (T2DM). Here, we investigated the potential mechanisms to explain the lower T2DM risk observed among individuals following plant-based diets.MethodsProspective data from the UK Biobank, a cohort study of participants aged 40 to 69 years at baseline, was evaluated. Associations between healthful and unhealthful plant-based indices (hPDI and uPDI) and T2DM risk were analysed by multivariable Cox regression models, followed by causal mediation analyses to investigate which cardiometabolic risk factors explained the observed associations.ResultsOf 113,097 study participants 2,628 developed T2DM over 12 years of follow-up. Participants with the highest hPDI scores (Quartile 4) had a 24% lower T2DM risk compared to those with the lowest scores (Quartile 1) [Hazard Ratio (HR): 0.76, 95% Confidence Interval (CI): 0.68-0.85]. This association was mediated by a lower BMI (proportion mediated: 28%), lower waist circumference (28%), and lower concentrations of HBA1c (11%), triglycerides (9%), alanine aminotransferase (5%), gamma glutamyl transferase (4%), C-reactive protein (4%), insulin-like growth factor 1 (4%), cystatin C (4%) and urate (4%). Higher uPDI scores were associated with a 37% higher T2DM risk [HR: 1.37, 95% CI:1.22- 1.53], with higher waist circumference (proportion mediated: 17%), BMI (7%), and higher concentrations of triglycerides (13%) potentially playing mediating roles.ConclusionHealthful plant-based diets may protect against T2DM via lower body fatness, but also via normoglycaemia, lower basal inflammation as well as improved kidney and liver function

Effects of polyphenol, measured by a biomarker of total polyphenols in urine, on cardiovascular risk factors after a long-term follow-up in the PREDIMED Study.

Several epidemiological studies have shown an inverse association between the consumption of polyphenol-rich foods and risk of cardiovascular diseases. However, accuracy and reliability of these studies may be increased using urinary total polyphenol excretion (TPE) as a biomarker for total polyphenol intake. Our aim was to assess if antioxidant activity, measured by a Folin-Ciocalteu assay in urine, is correlated with an improvement in cardiovascular risk factors (blood pressure and serum glucose, cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations) in an elderly population at high risk. A longitudinal study was performed with 573 participants (aged 67.3 ± 5.9) from the PREDIMED study (ISRCTN35739639). We used Folin-Ciocalteu method to determine TPE in urine samples, assisting with solid phase extraction. Participants were categorized into three groups according to changes in TPE. Multiple linear regression models were used to assess relationships between TPE and clinical cardiovascular risk factors, adjusting for potential confounders. After a 5-year follow-up, significant inverse correlations were observed between changes in TPE and plasma triglyceride concentration (β = -8.563; P = 0.007), glucose concentration (β = -4.164; P = 0.036), and diastolic blood pressure (β = -1.316; P = 0.013). Our results suggest that the consumption of more polyphenols, measured as TPE in urine, could exert a protective effect against some cardiovascular risk factors.This study was supported by CICYT (AGL2013-49083- C3-1-R) from the Spanish Ministry of Economy and Competitiveness (MEC), the Generalitat de Catalunya (GC) 2014 SGR 773 and Instituto de Salud Carlos III, ISCIII (CIBEROBN). CIBEROBN is an initiative of ISCIII, Spain. Xiaohui Guo received support from China Scholarship Council (CSC). Alexander Medina-Remon thanks the ´“Juan de la Cierva” postdoctoral program (JCI-2012-13463) from ME

Polyphenol Levels Are Inversely Correlated with Body Weight and Obesity in an Elderly Population after 5 Years of Follow Up (The Randomised PREDIMED Study)

Overweight and obesity have been steadily increasing in recent years and currently represent a serious threat to public health. Few human studies have investigated the relationship between polyphenol intake and body weight. Our aim was to assess the relationship between urinary polyphenol levels and body weight. A cross-sectional study was performed with 573 participants from the PREDIMED (Prevención con Dieta Mediterránea) trial (ISRCTN35739639). Total polyphenol levels were measured by a reliable biomarker, total urinary polyphenol excretion (TPE), determined by the Folin-Ciocalteu method in urine samples. Participants were categorized into five groups according to their TPE at the fifth year. Multiple linear regression models were used to assess the relationships between TPE and obesity parameters; body weight (BW), body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR). After a five years follow up, significant inverse correlations were observed between TPE at the 5th year and BW (β = −1.004; 95% CI: −1.634 to −0.375, p = 0.002), BMI (β = −0.320; 95% CI: −0.541 to −0.098, p = 0.005), WC (β = −0.742; 95% CI: −1.326 to −0.158, p = 0.013), and WHtR (β = −0.408; 95% CI: −0.788 to −0.028, p = 0.036) after adjustments for potential confounders. To conclude, a greater polyphenol intake may thus contribute to reducing body weight in elderly people at high cardiovascular risk. Nutrients 2017, 9, 452; doi:10.3390/nu905045

Total urinary polyphenol excretion: a biomarker of an anti-inflammatory diet and metabolic syndrome status

Background: Chronic inflammation is associated with noncommunicable diseases, including obesity, metabolic syndrome (MetS), and CVDs. The Mediterranean diet has been shown to have strong anti-inflammatory effects, attributed in part to the polyphenol richness of many of its components. Objectives: This study aimed to assess the value of polyphenols as a urinary biomarker of an anti-inflammatory diet and their influence on MetS status. Methods: A longitudinal analysis was performed in Spain considering 543 participants with high CVD risk in a PREDIMED study. Approximately 52% of the participants were women and 48% were men with a mean age of 67.5 (5.9) y. Total polyphenol excretion (TPE) in urine was determined at baseline and 5 y of intervention using a validated Folin-Ciocalteu spectrophotometric method, and the dietary inflammatory index (DII) was calculated from a validated 137-item food-frequency questionnaire. Three categories were built according to tertiles of change in the DII score. Multivariable linear regression analyses were performed to assess the association of changes in TPE with changes in the DII scores and with MetS status at 5 y. Results: Tertiles 2 and 3 compared with tertile 1 presented a lower anti-inflammatory potential of the diet and were inversely associated with TPE in women [-0.30 mg gallic acid equivalent (GAE)/g creatinine; 95% CI: -0.46, -0.15; P value = 0.006 and -0.29 mg GAE/g creatinine; 95% CI: -0.43, -0.15; P value = 0.005], respectively. The mean changes in TPE were 7.9 (56.1) mg GAE/g creatinine in women and 7.7 (48.2) mg GAE/g creatinine in men. In addition, TPE was inversely associated with changes in MetS status [-0.06 (-0.09; -0.02), P value = 0.009] in both men and women. Conclusions: Urinary polyphenols may be a potential biomarker of anti-inflammatory diet consumption in women and are prospectively associated with improvement in MetS.This research has been supported by the CICYT [AGL2016- 75329-R PID2020-114022RB-I00], CIBEROBN from the Instituto de Salud Carlos III, ISCIII from the Ministerio de Ciencia, Innovación y Universidades, (AEI/FEDER, UE), and Generalitat de Catalunya (GC) [2021-SGR-00334] and NIH “Mediterranean diet, Metabolites, and Cardiovascular Disease” (2R01HL118264-09) funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript