PREvención Con DIeta MEDiterránea Research Articles

Obesity pillars roundtable: Obesity and individuals from the Mediterranean region and Middle East

BackgroundThe rates of obesity in Mediterranean and Middle East regions are increasing. This may be related to worsening physical inactivity, and gravitation away from more healthful nutrition. MethodsThis roundtable discussion includes 4 obesity specialists with experience in the clinical management of obesity. Included in this discussion are citations regarding obesity and populations from the Mediterranean and Middle East regions. ResultsAmong the most studied nutritional dietary pattern having evidence-based data supporting improved cardiometabolic health is the Mediterranean Diet. Prospective studies such as the PREvención con DIeta MEDiterránea (PREDIMED) study support the cardiometabolic benefits of dietary consumption of plant-based, higher fiber foods having a relatively high proportion of unsaturated fats. Cuisine from the Middle East has both similarities and some differences compared to the Mediterranean Diet. Interim analyses of the PREDIMED-Plus study suggest the Mediterranean Diet plus caloric restriction and physical activity intervention reduces body weight and improves cardiometabolic risk factors. As with any dietary intake, Mediterranean and Middle Eastern food choices and preparation affect their nutritional healthfulness. ConclusionThe panelists of this roundtable discussion describe their practical diagnostic processes and treatment plans for patients with obesity from the Mediterranean Region and Middle East.

Cross-Sectional Associations between HDL Structure or Function, Cell Membrane Fatty Acid Composition, and Inflammation in Elderly Adults

BackgroundCell membrane fatty acid composition has been related to inflammation and cardiovascular disease (CVD) risk. Dysregulation of HDL function is also considered a CVD risk factor. ObjectivesWe aimed to investigate whether the content of cell membrane fatty acids and HDL functionality are linked to each other as well as to inflammation. MethodsThis cross-sectional analysis involved 259 participants (mean age: 67.9 y) with overweight/obesity (mean BMI: 29.5 kg/m2) from a coronary artery disease case-control study nested within the PREDIMED (PREvención con DIeta MEDiterránea) trial for which HDL functional parameters [apoA-I, apoA-IV, and apoC-III; cholesterol efflux capacity (CEC); HDL oxidative inflammatory index (HOII); sphingosine-1-phosphate (S1P); serum amyloid A (SAA); and complement-3 (C3) protein] were quantified. We also assessed 22 fatty acids in blood cell membranes using GC and inflammatory markers (IFN-γ and IL-1b, IL-6, IL-8, and IL-10) in serum. Associations of HDL-related variables with cell membrane fatty acids and with inflammatory markers were assessed using multivariable linear regression analyses with elastic net penalty. ResultsApoA-I, apoC-III, CEC, HOII, S1P, and SAA, but not apoA-IV and C3 protein, were associated with membrane fatty acids. S1P and SAA were directly associated with IL-6, whereas apoA-I and C3 protein showed inverse associations with IL-6. Specific fatty acids including myristic acid (14:0) and long-chain n–6 fatty acids being negatively and positively associated with IL-8, respectively, were also found to be positively associated with SAA. ConclusionsThis study suggests interrelations between indicators of inflammation and both blood cell membrane fatty acid composition and HDL structure/functional parameters in a Mediterranean population at high CVD risk.This trial was registered at http://www.isrctn.com www.isrctn.com as ISRCTN35739639.

Chronotype: A Tool to Screen Eating Habits in Polycystic Ovary Syndrome?

Polycystic ovary syndrome (PCOS) is the most common endocrine disorders in women of reproductive age, whose lifestyle approach is an essential part of the treatment. Recently, chronotype, i.e., a trait that determines individual’s circadian preference in behavioral and biological rhythms, has been reported to play a role in determining nutrition preferences and the risk of developing chronic diseases. Thus, the aim of this study was to investigate if chronotype categories (morning, evening, and neither) could be used as tool to screen eating habits in women with PCOS. In this observational cross-sectional study, we assessed anthropometric measurements, lifestyle habits, chronotype categories, adherence to the Mediterranean Diet, dietary pattern, and metabolic parameters in 112 women with PCOS. Chronotype was classified as morning in 27.7%, evening in 42.9%, and neither in 29.5% of subjects. Women with PCOS with evening chronotype showed significantly higher percentages of grade I (p = 0.003) and grade II obesity (p = 0.001), did less regular exercise (p < 0.001), and most of them were smokers (p < 0.001) compared to those with neither and morning chronotypes. Women with PCOS with evening chronotype were significantly more insulin resistant (Homeostatic Model Assessment of Insulin Resistance (HoMA-IR) cut off > 2.5) than other two chronotypes (p < 0.001). Women with PCOS with evening chronotype had the lowest PREvención con DIetaMEDiterránea (PREDIMED) score, consumed more calories (p < 0.001), total (p < 0.001) and simple carbohydrates (p < 0.001), total fat (p < 0.001) and saturated fatty acids (p < 0.001), polyunsaturated fatty acids (p < 0.001) and n-6 polyunsaturated fatty acids (p < 0.001), and less fiber (p < 0.001) than women with PCOS with other chronotypes. In addition, women with PCOS with evening chronotype consumed less extra virgin olive oil (p = 0.001), legumes (p = 0.038), fish/seafood (p < 0.001), and tree nuts (p = 0.041) than women with PCOS of the other two chronotype categories and less red wine (p < 0.001) and more red/processed meat (p < 0.001) than women with PCOS with morning chronotype. In conclusion, in women with PCOS, evening chronotype has been associated with a most severe insulin resistance and unhealthiest eating habits. Thus, chronotype assessment could be an effective tool to screen the eating habits, and more generally the lifestyle, of women with PCOS.

Potential Benefits of the Mediterranean Diet and Physical Activity in Patients with Hidradenitis Suppurativa: A Cross-Sectional Study in a Spanish Population.

There is scarce scientific information regarding the potential benefits of healthy lifestyles in patients with hidradenitis suppurativa (HS). The objective of this study is to explore the potential association between the adherence to a Mediterranean diet (MD), physical activity and HS severity. A cross-sectional study that included patients with HS was conducted. Disease severity was evaluated by the International Hidradenitis Suppurativa Severity Score System (IHS4) and self-reported disease activity using a Numeric Rating Scale (NRS, 0–10). The adherence to a MD was assessed by the PREvención con DIeta MEDiterránea (PREDIMED) questionnaire and the level of physical activity by the International Physical Activity questionnaire. A total of 221 patients with HS were included in our study. The adherence to a MD was average for a Spanish population. A higher adherence to a MD was associated with lower disease activity, lower self-reported Hurley and lower IHS4. The use of extra virgin olive oil as the main culinary lipid was the dietary habit that implied a lower degree of disease activity (p < 0.05). Regarding physical activity, both the self-reported severity and IHS4 presented an inverse association with the intensity of physical activity. The adherence to a MD and the intensity of physical activity were positively associated. The Mediterranean dietary pattern may have an impact on HS. Greater adherence to a MD is related to lower HS severity and more physical activity also correlates to lower disease severity. The MD could be an appropriate dietary pattern for patients with HS due to its anti-inflammatory properties, and combining this with increased levels of physical activity could have additional benefits.

Acilcarnitinas en plasma y riesgo de insuficiencia cardiaca y fibrilación auricular: el estudio Prevención con dieta mediterránea

Introduction and objectivesFatty acid metabolic dysregulation in mitochondria is a common mechanism involved in the development of heart failure (HF) and atrial fibrillation (AF). We evaluated the association between plasma acylcarnitine levels and the incidence of HF or AF, and whether the mediterranean diet (MedDiet) may attenuate the association between acylcarnitines and HF or AF risk. MethodsTwo case-control studies nested within the Prevención con dieta mediterránea (PREDIMED) trial. High cardiovascular risk participants were recruited in Spain: 326 incident HF and 509 AF cases individually matched to 1 to 3 controls. Plasma acylcarnitines were measured with high-throughput liquid chromatography-tandem mass spectrometry. Conditional logistic regression models were fitted to estimate multivariable OR and 95%CI. Additive and multiplicative interactions were assessed by intervention group, obesity (body mass index ≥ 30 kg/m2), and type 2 diabetes. ResultsElevated levels of medium- and long-chain acylcarnitines were associated with increased HF risk (adjusted ORperDE, 1.28; 95%CI, 1.09-1.51 and adjusted ORperDE, 1.21; 95%CI, 1.04-1.42, respectively). A significant association was observed for AF risk with long-chain acylcarnitines: 1.20 (1.06-1.36). Additive interaction of the association between long-chain acylcarnitines and AF by the MediDiet supplemented with extra virgin olive oil (P for additive interaction=.036) and by obesity (P=.022) was observed in an inverse and direct manner, respectively. ConclusionsAmong individuals at high cardiovascular risk, elevated long-chain acylcarnitines were associated with a higher risk of incident HF and AF. An intervention with MedDiet+extra-virgin olive oil may reduce AF risk associated with long-chain acylcarnitines.This trial was registered at controlled-trials.com (Identifier: ISRCTN35739639).Full English text available from:www.revespcardiol.org/en

Adherence to the Mediterranean diet and the impact on clinical features in primary Sjögren's syndrome.

The relationship between dietary patterns, including the Mediterranean diet, and rheumatic and musculoskeletal diseases (RMDs) has been increasingly assessed but data on patients with established primary Sjögren's syndrome (pSS) is lacking. The aim of the study was to explore the adherence to the Mediterranean diet and its relationship with metabolic and inflammatory features in a cohort of patients with pSS. Demographic, clinical and serological data, including anthropometric parameters and cardiovascular (CV) disease risk factors/events among others were collected from 91 pSS patients. Adherence to the Mediterranean diet over the previous 12 months was assessed with the 14-item PREvencion con DIeta MEDiterranea (PREDIMED) tool and the 28-item Mediterranean Lifestyle (MEDLIFE) index. According to the PREDIMED score 29 (31%) patients had a good adherence to the Mediterranean Diet, 57 (61%) a medium adherence and only 7 (8%) a poor adherence. No difference could be identified across groups with regard to demographic data, disease activity, CV risk factors or other parameters. With regard to the MEDLIFE, the total of blocks 1 and 2, that are related to Mediterranean foods and dietary habits, did not correlate with the total of block 3 (related to other healthy habits such as physical activity), meaning that the patients adhering the most to the Mediterranean Diet not necessarily had an overall healthy lifestyle. The PREDIMED score was inversely correlated with disease activity, as measured by ESSDAI (Spearman's rho=-0.27, p=0.009) and ClinESSDAI (Spearman's rho=-0.26, p=0.01). Fish consumption was associated with lower prevalence of hypertension. Adherence to the Mediterranean diet, with particular attention to fish consumption, may be beneficial on various domains in pSS, such as the CV system and the inflammatory environment, and as such should be recommended to patients with this disease.

Plasma acylcarnitines and risk of incident heart failure and atrial fibrillation: the Prevención con dieta mediterránea study

Introduction and objectivesFatty acid metabolic dysregulation in mitochondria is a common mechanism involved in the development of heart failure (HF) and atrial fibrillation (AF). We evaluated the association between plasma acylcarnitine levels and the incidence of HF or AF, and whether the mediterranean diet (MedDiet) may attenuate the association between acylcarnitines and HF or AF risk. MethodsTwo case-control studies nested within the Prevención con dieta mediterránea (PREDIMED) trial. High cardiovascular risk participants were recruited in Spain: 326 incident HF and 509 AF cases individually matched to 1 to 3 controls. Plasma acylcarnitines were measured with high-throughput liquid chromatography-tandem mass spectrometry. Conditional logistic regression models were fitted to estimate multivariable OR and 95%CI. Additive and multiplicative interactions were assessed by intervention group, obesity (body mass index ≥ 30 kg/m2), and type 2 diabetes. ResultsElevated levels of medium- and long-chain acylcarnitines were associated with increased HF risk (adjusted ORperDE, 1.28; 95%CI, 1.09-1.51 and adjusted ORperDE, 1.21; 95%CI, 1.04-1.42, respectively). A significant association was observed for AF risk with long-chain acylcarnitines: 1.20 (1.06-1.36). Additive interaction of the association between long-chain acylcarnitines and AF by the MediDiet supplemented with extra virgin olive oil (P for additive interaction=.036) and by obesity (P=.022) was observed in an inverse and direct manner, respectively. ConclusionsAmong individuals at high cardiovascular risk, elevated long-chain acylcarnitines were associated with a higher risk of incident HF and AF. An intervention with MedDiet+extra-virgin olive oil may reduce AF risk associated with long-chain acylcarnitines.This trial was registered at controlled-trials.com (Identifier: ISRCTN35739639).

Metabolomics of the tryptophan–kynurenine degradation pathway and risk of atrial fibrillation and heart failure: potential modification effect of Mediterranean diet

The tryptophan-kynurenine pathway is linked to inflammation. We hypothesize that metabolites implicated in this pathway may be associated with the risk of heart failure (HF) or atrial fibrillation (AF) in a population at high risk of cardiovascular disease. We aimed to prospectively analyze the associations of kynurenine-related metabolites with the risk of HF and AF and to analyze a potential effect modification by the randomized interventions of the PREDIMED (Prevención con Dieta Mediterránea) trial with Mediterranean diet (MedDiet). Two case-control studies nested within the PREDIMED trial were designed. We selected 324 incident HF cases and 502 incident AF cases individually matched with ≤3 controls. Conditional logistic regression models were fitted. Interactions with the intervention were tested for each of the baseline plasma metabolites measured by LC-tandem MS. Higher baseline kynurenine:tryptophan ratio (OR for 1 SD: 1.20; 95% CI: 1.01, 1.43) and higher levels of kynurenic acid (OR: 1.19; 95% CI: 1.01, 1.40) were associated with HF. Quinolinic acid was associated with AF (OR: 1.15; 95% CI: 1.01, 1.32) and HF (OR: 1.25; 95% CI: 1.04, 1.49). The MedDiet intervention modified the positive associations of kynurenine (Pinteraction=0.006), kynurenic acid (Pinteraction=0.008), and quinolinic acid (Pinteraction=0.033) with HF and the association between kynurenic acid and AF (Pinteraction =0.02). We found that tryptophan-kynurenine pathway metabolites were prospectively associated with higher HF risk and to a lesser extent with AF risk. Moreover, an effect modification by MedDiet was observed for the association between plasma baseline kynurenine-related metabolites and the risk of HF, showing that the positive association of increased levels of these metabolites and HF was restricted to the control group.

Modulation of Telomere Length by Mediterranean Diet, Caloric Restriction, and Exercise: Results from PREDIMED-Plus Study.

Telomere length (TL) has been associated with aging and is determined by lifestyle. However, the mechanisms by which a dietary pattern such as the Mediterranean diet (MedDiet) affects TL homeostasis are still unknown. Our aim was to analyse the effect of an energy-restricted MedDiet with physical activity promotion (intervention group) versus an unrestricted-caloric MedDiet with no weight-loss advice (control group) on TL and 8-hydroxydeoxyguanosine (8-OHdG) plasma levels. In total, 80 non-diabetic participants with metabolic syndrome were randomly selected from the PREDIMED (PREvención con DIeta MEDiterránea)-Plus-Reus study. TL was measured by a hybridisation method and 8-OHdG levels by ELISA at baseline and after one year of intervention. Linear mixed models (LMM)—raw and after adjusting for potential confounders—were used to examine the associations between TL or 8-OHdG plasma levels by intervention group and/or time. A total of 69 subjects with available DNA samples were included in the analyses. A significant β-coefficient was found for time towards increasing values through the year of follow-up for TL (unadjusted β of 0.740 (95% CI: 0.529 to 0.951), and multivariable model β of 0.700 (95% CI: 0.477 to 0.922)). No significant βs were found, neither for the intervention group nor for the interaction between the intervention group and time. Regarding 8-OHdG plasma levels, no significant βs were found for the intervention group, time, and its interaction. Our results suggest that MedDiet could have an important role in preventing telomere shortening, but calorie restriction and exercise promotion did not provide an additional advantage concerning telomere length after one year of MedDiet intervention.

Urinary Tartaric Acid, a Biomarker of Wine Intake, Correlates with Lower Total and LDL Cholesterol.

Postmenopausal women are at higher risk of developing cardiovascular diseases due to changes in lipid profile and body fat, among others. The aim of this study was to evaluate the association of urinary tartaric acid, a biomarker of wine consumption, with anthropometric (weight, waist circumference, body mass index (BMI), and waist-to-height ratio), blood pressure, and biochemical variables (blood glucose and lipid profile) that may be affected during the menopausal transition. This sub-study of the PREDIMED (Prevención con Dieta Mediterránea) trial included a sample of 230 women aged 60–80 years with high cardiovascular risk at baseline. Urine samples were diluted and filtered, and tartaric acid was analyzed by liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Correlations between tartaric acid and the study variables were adjusted for age, education level, smoking status, physical activity, BMI, cholesterol-lowering, antihypertensive, and insulin treatment, total energy intake, and consumption of fruits, vegetables, and raisins. A strong association was observed between wine consumption and urinary tartaric acid (0.01 μg/mg (95% confidence interval (CI): 0.01, 0.01), p-value < 0.001). Total and low-density lipoprotein (LDL) cholesterol were inversely correlated with urinary tartaric acid (−3.13 μg/mg (−5.54, −0.71), p-value = 0.016 and −3.03 μg/mg (−5.62, −0.42), p-value = 0.027, respectively), whereas other biochemical and anthropometric variables were unrelated. The results suggest that wine consumption may have a positive effect on cardiovascular health in postmenopausal women, underpinning its nutraceutical properties.

Validity of the energy-restricted Mediterranean Diet Adherence Screener

Short dietary assessment tools can be useful to estimate food intake and diet quality in large-scale epidemiological studies with time constraints.To determine the concurrent validity of the 17-item energy-restricted Mediterranean Adherence Screener (er-MEDAS) used in the PREDIMED (PREvención con DIeta MEDiterránea)-Plus trial and to analyse its capacity to detect 1-year changes in diet and cardiometabolic risk factors.Validation study nested in the PREDIMED-Plus (n = 6760, 55-75 years). Dietary data were collected by the 17-item er-MEDAS and a 143-item validated semiquantitative food frequency questionnaire (FFQ) at baseline and after 1-year intervention. Cardiometabolic risk markers were measured at both time points. A Mediterranean diet (MedDiet) score was derived from both instruments. Concurrent validity was evaluated by Pearson and intra-class correlation coefficients (ICC) and Bland and Altman limits of agreement. Construct validity was evaluated by assessing 1-year changes in FFQ-reported dietary intake and cardiometabolic profile changes in relation to changes in er-MEDAS.A moderate to good correlation between the MedDiet score calculated by both measurement instruments was found: r = 0.61 and ICC = 0.60 (both p < 0.001). Agreement of each of the er-MEDAS items ranged from 55.4% to 85.0% with a moderate mean concordance (kappa = 0.41). Between baseline and 1-year follow-up, energy intake measured by the FFQ decreased by 242 kcal, while Mediterranean food consumption increased in participants with the highest increase in the er-MEDAS MedDiet score. An increase in the er-MEDAS MedDiet score ratings was associated with a decrease in BMI, waist circumference, triglycerides, fasting glucose, diastolic blood pressure, and triglycerides/HDL-cholesterol ratio (p < 0.001 for all), and with an increase in HDL-cholesterol (p = 0.006).The er-MEDAS shows a modest to good concurrent validity compared with FFQ data. It shows acceptable construct validity, as a greater er-MEDAS score was associated with more favourable dietary and cardiometabolic profiles over time.ISRCTN89898870; registration date, 24 July 2014. https://www.isrctn.com/ISRCTN89898870.

Dairy consumption, plasma metabolites, and risk of type 2 diabetes

Epidemiologic studies have reported a modest inverse association between dairy consumption and the risk of type 2 diabetes (T2D). Whether plasma metabolite profiles associated with dairy consumption reflect this relationship remains unknown. We aimed to identify the plasma metabolites associated with total and specific dairy consumption, and to evaluate the association between the identified multi-metabolite profiles and T2D. The discovery population included 1833 participants from the Prevención con Dieta Mediterránea (PREDIMED) trial. The confirmatory cohorts included 1522 PREDIMED participants at year 1 of the trial and 4932 participants from the Nurses' Health Studies (NHS), Nurses' Health Study II (NHSII), and Health Professionals Follow-Up Study US-based cohorts. Dairy consumption was assessed using validated FFQs. Plasma metabolites (n=385) were profiled using LC-MS. We identified the dairy-related metabolite profiles using elastic net regularized regressions with a 10-fold cross-validation procedure. We evaluated the associations between the metabolite profiles and incident T2D in the discovery and the confirmatory cohorts. Total dairy intake was associated with 38 metabolites. C14:0 sphingomyelin (positive coefficient), C34:0 phosphatidylethanolamine (positive coefficient), and γ-butyrobetaine (negative coefficient) were associated in a directionally similar fashion with total and specific (milk, yogurt, cheese) dairy consumption. The Pearson correlation coefficients between self-reported total dairy intake and predicted total dairy intake based on the corresponding multi-metabolite profile were 0.37 (95% CI, 0.33-0.40) in the discovery cohort and 0.16 (95% CI, 0.13-0.19) in the US confirmatory cohort. After adjusting for T2D risk factors, a higher total dairy intake-related metabolite profile score was associated with a lower T2D risk [HR per 1 SD; discovery cohort: 0.76 (95% CI, 0.63-0.90); US confirmatory cohort: 0.88 (95% CI, 0.78-0.99)]. Total dairy intake was associated with 38 metabolites, including 3 consistently associated with dairy subtypes (C14:0 sphingomyelin, C34:0 phosphatidylethanolamine, γ-butyrobetaine). A score based on the 38 identified metabolites showed an inverse association with T2D risk in Spanish and US populations.

Mediterranean Diet and cardiovascular health: an historical perspective.

The first investigation of dietary intake in the Mediterranean region was undertaken at the initiative of the government of Greece in 1948. Plant foods (cereals, pulses, nuts, potatoes, vegetables and fruits) accounted for 61 % of total energy intake (TEI), animal foods (meat, eggs, fish and dairy products) for 7 % of TEI and olive oil was the main oil used. In 1950s, Ancel Keys undertook studies in USA, Italy, Spain, England, Japan, Australia and Canada leading him to hypothesise that a link could exist between diet, plasma cholesterol and CHD. Between 1958 and 1964, Keys and co-workers carried out the Seven Countries Study, which enrolled men aged 40-59 years in one of sixteen cohorts from seven countries (Finland, Greece, Italy, Yugoslavia, Japan, USA and Italy). After 15-, 25- and 50-year follow-up, a strong positive relation was observed between saturated fat intake and CHD mortality, and a negative one with Mediterranean Dietary Index. In 1975, Keys and his wife published a book entitled: 'How to eat well and stay well. The Mediterranean way', which popularised Mediterranean Diet (MedDiet). After 45-year follow-up, longevity without CHD death was 12·9 years higher in Crete than in Finland. Protecting effect of MedDiet towards CHD incidence and risk is now confirmed by Prevencion con Dieta Mediterranea study and by cohorts' studies gathered in several recent meta-analyses. MedDiet is sustainable and recognised by UNESCO as an intangible cultural heritage, which is the most beautiful homage that can be paid to Ancel Keys and all his co-workers.

The Association between Dietary Inflammatory Index and Sex Hormones among Men in the United States.

This study investigated the association between Dietary Inflammatory Index and sex hormones in a large, nationally representative adult male sample. We utilized data from the 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey. Males aged ≥20 years who provided a 24-hour dietary intake history and underwent serum sex hormone testing were included in analysis. Weighted proportions and multivariable analysis controlling for age, race, energy, smoking status, education level, body mass index and time of venipuncture were used to evaluate the associations between Dietary Inflammatory Index and sex hormones. For 4,151 participants, Dietary Inflammatory Index ranged from -5.05 to 5.48. Mean±SD total testosterone was 419.30±176.27 ng/dl. Mean±SD total testosterone was lower among men in the highest tertile compared with men in the lowest tertile group (410.42±171.97 vs 422.71±175.69, p <0.001). A per unit increase in Dietary Inflammatory Index was related to 4.0% (95% CI 0.5-7.6) higher odds of testosterone deficiency. In the fully adjusted multivariable model, males in Dietary Inflammatory Index tertile 3 (the most pro-inflammatory) had 29.6% (3.1-63.0) higher odds of testosterone deficiency than those in tertile 1 (p trend=0.025). Interaction tests revealed no significant effect of body mass index on the association of Dietary Inflammatory Index with testosterone deficiency and all sex hormone parameters. Men adhering to a more pro-inflammatory diet appear to have a higher risk of testosterone deficiency, indicating the important role of diet in male reproductive health.

Longitudinal changes in adherence to the portfolio and DASH dietary patterns and cardiometabolic risk factors in the PREDIMED-Plus study

The Portfolio and Dietary Approaches to Stop Hypertension (DASH) diets have been shown to lower cardiometabolic risk factors in randomized controlled trials (RCTs). However, the Portfolio diet has only been assessed in RCTs of hyperlipidemic patients. Therefore, to assess the Portfolio diet in a population with metabolic syndrome (MetS), we conducted a longitudinal analysis of one-year data of changes in the Portfolio and DASH diet scores and their association with cardiometabolic risk factors in Prevención con Dieta Mediterránea (PREDIMED)-Plus trial. PREDIMED-Plus is an ongoing clinical trial (Trial registration: ISRCTN89898) conducted in Spain that includes 6874 older participants (mean age 65y, 48% women) with overweight/obesity fulfilling at least three criteria for MetS. Data for this analysis were collected at baseline, six months and one year. Adherence to the Portfolio and DASH diet scores were derived from a validated 143-item food frequency questionnaire. We used linear mixed models to examine the associations of 1-SD increase and quartile changes in the diet scores with concomitant changes in cardiometabolic risk factors. After adjusting for several potential confounders, a 1-SD increase in the Portfolio diet score was significantly associated with lower HbA1c (β [95% CI]:-0.02% [-0.02,-0.01], P<0.001), fasting glucose (-0.47mg/dL [-0.83,-0.11], P=0.01), triglycerides (-1.29mg/dL [-2.31,-0.28], P=0.01), waist circumference (WC) (-0.51cm [-0.59,-0.43], P<0.001), and body mass index (BMI) (-0.17kg/m2 [-0.19,-0.15], P<0.001). A 1-SD increase in the DASH diet score was significantly associated with lower HbA1c (-0.03% [-0.04,-0.02], P<0.001), glucose (-0.84mg/dL [-1.18,-0.51], P<0.001), triglycerides (-3.38mg/dL [-4.37,-2.38], P<0.001), non-HDL-cholesterol (-0.47mg/dL [-0.91,-0.04], P=0.03), WC (-0.69cm [-0.76,-0.60cm], P<0.001), BMI (-0.25kg/m2 [-0.28,-0.26kg/m2], P<0.001), systolic blood pressure (-0.57mmHg [-0.81,-0.32mmHg], P<0.001), diastolic blood pressure (-0.15mmHg [-0.29,-0.01mmHg], P=0.03), and with higher HDL-cholesterol (0.21mg/dL [0.09, 0.34mg/dL, P=0.001]). Similar associations were seen when both diet scores were assessed as quartiles, comparing extreme categories of adherence. Among older adults at high cardiovascular risk with MetS, greater adherence to the Portfolio and DASH diets showed significant favourable prospective associations with several clinically relevant cardiometabolic risk factors. Both diets are likely beneficial for cardiometabolic risk reduction.

Physical Activity and Adherence to the Mediterranean Diet among Spanish Employees in a Health-Promotion Program before and during the COVID-19 Pandemic: The Sanitas-Healthy Cities Challenge.

Physical activity and a healthy diet are key factors for avoiding major noncommunicable diseases. The aim of the present study was to analyze how physical activity (PA) and adherence to the Mediterranean diet among employees participating in the Healthy Cities program have been affected during confinement due to the COVID-19 pandemic. The sample was composed of 297 employees from 40 leading companies based in Spain, who participated in the 5th edition of the Sanitas “Healthy Cities” challenge. The participants (148 women and 149 men), aged between 24 and 63 years old (M = 42.76; SD = 7.79) completed the short form of the International Physical Activity Questionnaire (IPAQ) and the PREDIMED (Prevención con Dieta Mediterránea) questionnaire to measure adherence to the Mediterranean diet before and during the pandemic. Pearson χ2 tests revealed that workers were more likely to show sedentary behaviors during the pandemic than before (83.5% vs. 66.7%). Additionally, they were more likely to reach high levels of PA (51.2% vs. 64%), and Wilcoxon tests revealed that energy expenditure measured in Metabolic Equivalent of Task (MET) was higher during the pandemic (4199.03 METs) than before (3735.32 METs), due to an increase in moderate PA. Lastly, a higher adherence to a Mediterranean diet during the pandemic (76.4%) than before (54.5%) was reported. The findings of this investigation suggest a positive effect of working from home for employees involved in a health-promotion program, and highlight the relevance of this kind of action among this population.

Mediterranean Diet Maintained Platelet Count within a Healthy Range and Decreased Thrombocytopenia-Related Mortality Risk: A Randomized Controlled Trial.

There is little information on the dietary modulation of thrombosis-related risk factors such as platelet count. We aimed to assess the effects of Mediterranean diet (MedDiet) on platelet count and related outcomes in an older population at high cardiovascular risk. In participants of the PREDIMED (PREvención con DIeta MEDiterránea) study, we assessed whether an intervention with a MedDiet enriched with extra-virgin olive oil or nuts, relative to a low-fat control diet, modulated platelet count (n = 4189), the risk of developing thrombocytosis and thrombocytopenia (n = 3086), and the association between these alterations and all-cause mortality (median follow-up time: 3.0 years). Although platelet count increased over time (+0.98·109 units/L·year [95% confidence interval: 0.12; 1.84]), MedDiet interventions moderated this increase, particularly in individuals with near-high baseline count (both MedDiets combined: −3.20·109 units/L·year [−5.81; −0.59]). Thrombocytopenia incidence was lower in the MedDiet interventions (incidence rates: 2.23% in control diet, 0.91% in MedDiets combined; hazard ratio: 0.44 [0.23; 0.83]). Finally, thrombocytopenia was associated with a higher risk of all-cause mortality (hazard ratio: 4.71 [2.69; 8.24]), but this relationship was attenuated in those allocated to MedDiet (p-interaction = 0.018). In brief, MedDiet maintained platelet counts within a healthy range and attenuated platelet-related mortality in older adults at high cardiovascular risk.

Walnut Consumption, Plasma Metabolomics, and Risk of Type 2 Diabetes and Cardiovascular Disease

Walnut consumption is associated with lower risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, it is unknown whether plasma metabolites related to walnut consumption are also associated with lower risk of cardiometabolic diseases. The study aimed to identify plasma metabolites associated with walnut consumption and evaluate the prospective associations between the identified profile and risk of T2D and CVD. The discovery population included 1833 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) study with available metabolomics data at baseline. The study population included 57% women (baseline mean BMI (in kg/m2): 29.9; mean age: 67 y). A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation population. Plasma metabolomics analyses were performed using LC-MS. Cross-sectional associations between 385 known metabolites and walnut consumption were assessed using elastic net continuous regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite weighted models and self-reported walnut consumption in each pair of training-validation data sets within the discovery population. We further estimated the prospective associations between the identified metabolite profile and incident T2D and CVD using multivariable Cox regression models. A total of 19 metabolites were significantly associated with walnut consumption, including lipids, purines, acylcarnitines, and amino acids. Ten-CV Pearson correlation coefficients between self-reported walnut consumption and the plasma metabolite profile were 0.16 (95% CI: 0.11, 0.20) in the discovery population and 0.15 (95% CI: 0.10, 0.20) in the validation population. The metabolite profile was inversely associated with T2D incidence (HR per 1 SD: 0.83; 95% CI: 0.71, 0.97; P=0.02). For CVD incidence, the HR per 1-SD was 0.71 (95% CI: 0.60, 0.85; P<0.001). A metabolite profile including 19 metabolites was associated with walnut consumption and with a lower risk of incident T2D and CVD in a Mediterranean population at high cardiovascular risk.

U-Shaped Association between Dietary Acid Load and Risk of Osteoporotic Fractures in 2 Populations at High Cardiovascular Risk

BackgroundBone contributes to maintaining the acid-base balance as a buffering system for blood pH. Diet composition also affects acid-base balance. Several studies have linked an imbalance in the acid-base system to changes in the density and structure of bone mass, although some prospective studies and meta-analyses suggest that acid load has no deleterious effect on bone. ObjectiveThe aim of this study was to examine the associations between potential renal acid load (PRAL) and net endogenous acid production (NEAP) and the risk of osteoporotic fractures and bone mineral density (BMD) in 2 middle-aged and elderly Mediterranean populations. MethodsWe conducted a longitudinal analysis including 870 participants from the PREvención con DIeta MEDiterranea (PREDIMED) Study and a cross-sectional analysis including 1134 participants from the PREDIMED-Plus study. Participants were adults, aged 55–80 y, either at high cardiovascular risk (PREDIMED) or overweight/obese with metabolic syndrome (PREDIMED-Plus), as defined by the International Diabetes Federation, the American Heart Association, and the National Heart Association. PRAL and NEAP were calculated from validated food-frequency questionnaires. BMD was measured using DXA scans. Fracture information was obtained from medical records. The association between mean PRAL and NEAP and fracture risk was assessed using multivariable-adjusted Cox models. BMD differences between tertiles of baseline PRAL and NEAP were evaluated by means of ANCOVA. ResultsA total 114 new fracture events were documented in the PREDIMED study after a mean of 5.2 y of intervention and 8.9 y of total follow-up. Participants in the first and third PRAL and NEAP tertiles had a higher risk of osteoporotic fracture compared with the second tertile, showing a characteristically U-shaped association [HR (95% CI): 1.73 (1.03, 2.91) in tertile 1 and 1.91 (1.14, 3.19) in tertile 3 for PRAL, and 1.83 (1.08, 3.09) in tertile 1 and 1.87 (1.10, 3.17) in tertile 3 for NEAP]. Compared with the participants in tertile 1, the participants in the top PRAL and NEAP tertiles had lower BMD [PRAL: mean total femur BMD: 1.029 ± 0.007 and 1.007 ± 0.007 g/cm2; P = 0.006 (tertiles 1 and 3); NEAP: mean total femur BMD: 1.032 ± 0.007 and 1.009 ± 0.007 g/cm2; P = 0.017 (tertiles 1 and 3)]. ConclusionsThe results of our study suggest that both high and low dietary acid are associated with a higher risk of osteoporotic fractures, although only high dietary acid was found to have a negative relation to BMD in senior adults with existing chronic health conditions. This trial was registered at http://www.isrctn.com/ as ISRCTN3573963 (PREDIMED) and ISRCTN89898870 (PREDIMED-Plus).

Plasma Metabolomic Profiles of Glycemic Index, Glycemic Load, and Carbohydrate Quality Index in the PREDIMED Study

BackgroundThe quality of carbohydrate consumed, assessed by the glycemic index (GI), glycemic load (GL), or carbohydrate quality index (CQI), affects the postprandial glycemic and insulinemic responses, which have been implicated in the etiology of several chronic diseases. However, it is unclear whether plasma metabolites involved in different biological pathways could provide functional insights into the role of carbohydrate quality indices in health. ObjectivesWe aimed to identify plasma metabolomic profiles associated with dietary GI, GL, and CQI. MethodsThe present study is a cross-sectional analysis of 1833 participants with overweight/obesity (mean age = 67 y) from 2 case-cohort studies nested within the PREDIMED (Prevención con Dieta Mediterránea) trial. Data extracted from validated FFQs were used to estimate the GI, GL, and CQI. Plasma concentrations of 385 metabolites were profiled with LC coupled to MS and associations of these metabolites with those indices were assessed with elastic net regression analyses. ResultsA total of 58, 18, and 57 metabolites were selected for GI, GL, and CQI, respectively. Choline, cotinine, γ-butyrobetaine, and 36:3 phosphatidylserine plasmalogen were positively associated with GI and GL, whereas they were negatively associated with CQI. Fructose-glucose-galactose was negatively and positively associated with GI/GL and CQI, respectively. Consistent associations of 21 metabolites with both GI and CQI were found but in opposite directions. Negative associations of kynurenic acid, 22:1 sphingomyelin, and 38:6 phosphatidylethanolamine, as well as positive associations of 32:1 phosphatidylcholine with GI and GL were also observed. Pearson correlation coefficients between GI, GL, and CQI and the metabolomic profiles were 0.30, 0.22, and 0.27, respectively. ConclusionsThe GI, GL, and CQI were associated with specific metabolomic profiles in a Mediterranean population at high cardiovascular disease risk. Our findings may help in understanding the role of dietary carbohydrate indices in the development of cardiometabolic disorders. This trial was registered at http://www.isrctn.com/ as ISRCTN35739639.