MedDiet Intervention Research Articles

Gut microbial metabolism of bile acids modifies the effect of Mediterranean diet interventions on cardiometabolic risk in a randomized controlled trial

ABSTRACT Bile acids (BAs) undergo extensive microbial metabolism in the gut and exert hormone-like functions on physiological processes underlying metabolic risk. However, the extent to which gut BA profiles predict cardiometabolic risk and explain individual responses to dietary interventions in humans is still unclear. In the DIRECT-PLUS Trial, we conducted a multi-omics analysis of 284 participants randomized into three groups: healthy dietary guidelines and two Mediterranean diet (MedDiet) groups. We longitudinally measured 44 fecal BAs using liquid chromatography-mass spectrometry, the gut microbiome through shotgun metagenomic sequencing, and body adiposity and serum lipids at baseline, 6, and 18 months. Fecal levels of 14 BAs, such as lithocholic acid and ursodeoxycholic acid, were prospectively associated with body mass index (BMI) and serum lipid profiles (false discovery rate [q]<0.05). Baseline fecal BA levels significantly modified the beneficial effects of the MedDiet; for example, BMI reduction induced by MedDiet interventions was more pronounced in individuals with lower 12-dehydrocholic acid levels (q-interaction <0.001). We confirmed that the gut microbiome is a major modifier of the secondary BA pool in humans. Furthermore, the association of fecal BAs with body adiposity and serum lipids varied significantly in individuals with different abundances of gut microbes carrying BA metabolism enzymes, e.g. several Ruminococcus spp. In summary, our study identifies novel predictive biomarkers for cardiometabolic risk and offers new mechanistic insights to guide personalized dietary interventions.

Early Mediterranean-Based Nutritional Intervention Reduces the Rate of Gestational Diabetes in Overweight and Obese Pregnant Women: A Post-Hoc Analysis of the San Carlos Gestational Prevention Study.

Obesity is a risk factor for the development of gestational diabetes mellitus (GDM). However, the most optimal type of nutritional intervention to prevent GDM in high-risk women is not clearly defined. This study investigates if nutritional treatment based on the Mediterranean diet (MedDiet) before the 12th gestational week (GW) in women at high risk due to a body mass index (BMI) ≥ 25 kg/m2 reduces the rate of GDM and metabolic syndrome (MetS) at 3 years postpartum. We performed a post-hoc analysis of the San Carlos Gestational Prevention Study. A total of 735 women with BMI ≥ 25 kg/m2 were evaluated between 2015 and 2018, with 246 in the standard diet control group (CG) and 489 in the MedDiet intervention group (IG). The rate of GDM was significantly lower in IG compared to CG (25.1% vs. 31.7%), relative risk (95% confidence interval), and 0.89 (0.78-0.99); p = 0.037. Postnatal follow-up was completed by 141 women in CG (57%) and 312 women in IG (64%). At 3 years postpartum, we observed a reduction in the rates of impaired fasting glucose (IFG) (0.51 (0.28-0.92); p = 0.019), obesity (0.51 (0.28-0.92); p = 0.041), waist circumference (WC) ≥ 89.5 cm (0.54 (0.31-0.94); p = 0.022), and MetS (0.56 (0.33-0.94); p = 0.003). MedDiet reduces the rate of GDM and postpartum MetS in women with BMI) ≥ 25 kg/m2, suggesting that its implementation should be routinely recommended from the first GWs.

Relationship between sex, APOE genotype, endocannabinoids and cognitive change in older adults with metabolic syndrome during a 3-year Mediterranean diet intervention

BackgroundThe Mediterranean diet (MedDiet) has demonstrated efficacy in preventing age-related cognitive decline and modulating plasma concentrations of endocannabinoids (eCBs) and N-acylethanolamines (NAEs, or eCB-like compounds), which are lipid mediators involved in multiple neurological disorders and metabolic processes. Hypothesizing that eCBs and NAEs will be biomarkers of a MedDiet intervention and will be related to the cognitive response, we investigated this relationship according to sex and apolipoprotein E (APOE) genotype, which may affect eCBs and cognitive performance.MethodsThis was a prospective cohort study of 102 participants (53.9% women, 18.8% APOE-ɛ4 carriers, aged 65.6 ± 4.5 years) from the PREDIMED-Plus-Cognition substudy, who were recruited at the Hospital del Mar Research Institute (Barcelona). All of them presented metabolic syndrome plus overweight/obesity (inclusion criteria of the PREDIMED-Plus) and normal cognitive performance at baseline (inclusion criteria of this substudy). A comprehensive battery of neuropsychological tests was administered at baseline and after 1 and 3 years. Plasma concentrations of eCBs and NAEs, including 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and N-docosahexaenoylethanolamine (DHEA), were also monitored. Baseline cognition, cognitive changes, and the association between eCBs/NAEs and cognition were evaluated according to gender (crude models), sex (adjusted models), and APOE genotype.ResultsAt baseline, men had better executive function and global cognition than women (the effect size of gender differences was − 0.49, p = 0.015; and − 0.42, p = 0.036); however, these differences became nonsignificant in models of sex differences. After 3 years of MedDiet intervention, participants exhibited modest improvements in memory and global cognition. However, greater memory changes were observed in men than in women (Cohen’s d of 0.40 vs. 0.25; p = 0.017). In men and APOE-ε4 carriers, 2-AG concentrations were inversely associated with baseline cognition and cognitive changes, while in women, cognitive changes were positively linked to changes in DHEA and the DHEA/AEA ratio. In men, changes in the OEA/AEA and OEA/PEA ratios were positively associated with cognitive changes.ConclusionsThe MedDiet improved participants’ cognitive performance but the effect size was small and negatively influenced by female sex. Changes in 2-AG, DHEA, the OEA/AEA, the OEA/PEA and the DHEA/AEA ratios were associated with cognitive changes in a sex- and APOE-dependent fashion. These results support the modulation of the endocannabinoid system as a potential therapeutic approach to prevent cognitive decline in at-risk populations.Trial registrationISRCTN89898870.

Mediterranean Diet adherence and wellbeing: a preliminary analysis of the MedWalk trial

Diet and diet quality have been linked to improvements to psychosocial health and wellbeing(1). However, data from national health surveys indicate that most Australian’s have poor diet quality and consume a Western style diet high in saturated fat, discretionary foods and added sugars and salt(2). The Mediterranean Diet (MedDiet), a predominantly plant-based diet rich in bioactive foods and nutrients, has been shown to improve mood and wellbeing. However, long-term effects beyond 6-months have not been thoroughly explored in older adults. MedWalk compares a 12-month MedDiet and Walking intervention with habitual lifestyle (HabDiet) in 160 older adults residing in retirement villages across South Australia and Victoria. Data from the South Australian cohort at baseline (n = 83) and 6-months (n = 74) are presented in this preliminary analysis.To determine dietary compliance, participants completed the 14-point MedDiet Adherence (MEDAS) questionnaire which assesses the intake of key MedDiet foods such as legumes, fish, and extra virgin olive oil; higher scores reflect higher adherence. Wellbeing was assessed using the Flourishing Index, which assesses life satisfaction, relationship satisfaction, happiness, mental and physical health. The total flourishing score includes 10 questions with a maximum of 100 points reflecting highest flourishing, while the secure flourishing score includes two additional questions related to safety, housing, and access to food with a maximum of 120 points to indicate highest flourishing. Group and time interactions for MEDAS and flourishing scores were analysed using linear mixed effects modelling. There were no significant differences between groups for MEDAS score at baseline (MedDiet 5.78 ± 0.34 vs HabDiet 5.74 ± 0.32). At 6 months, the MedDiet group had significantly increased their MEDAS by 4.16 points (P&lt;0.001), (MedDiet 10.0 ± 0.42 vs HabDiet (5.85 ± 0.39). At baseline there were no significant differences between groups for the total 10-point flourishing score (MedDiet 83.5 ± 2.01 vs HabDiet 82.1 ± 2.0) or 12-point secure flourishing score (MedDiet 100.6 ± 2.2 vs HabDiet 100.4 ± 2.2). At 6 months there was a significant between-group difference in total flourishing index scores with a mean difference of 6.97 points in the MedDiet group (MedDiet 85.8 ± 1.9 vs HabDiet 78.8 ± 1.8, P = 0.010). Similarly, the secure flourishing index score was 6.18 points higher in the MedDiet group compared to the HabDiet at 6-months (MedDiet 102.9 ± 2.2 vs HabDiet 96.8 ± 2.07, P = 0.046). Adhering to a MedDiet and walking intervention may lead to positive improvements to wellbeing in an older population. The flourishing index may need to be compared with other wellbeing questionnaires and instruments to better understand the relationship between wellbeing and MedDiet adherence as there was a cross-sectional association but no positive correlation at 6-months.

Intensive Weight-Loss Lifestyle Intervention Using Mediterranean Diet and COVID-19 Risk in Older Adults: Secondary Analysis of PREDIMED-Plus Trial

ObjectivesWe tested the effects of a weight-loss intervention encouraging energy-reduced MedDiet and physical activity (PA) in comparison to ad libitum MedDiet on COVID-19 incidence in older adults. DesignSecondary analysis of PREDIMED-Plus, a prospective, ongoing, multicentre randomized controlled trial. SettingCommunity-dwelling, free-living participants in PREDIMED-Plus trial. Participants6,874 Spanish older adults (55–75 years, 49% women) with overweight/obesity and metabolic syndrome. InterventionParticipants were randomised to Intervention (IG) or Control (CG) Group. IG received intensive behavioural intervention for weight loss with an energy-reduced MedDiet intervention and PA promotion. CG was encouraged to consume ad libitum MedDiet without PA recommendations. MeasurementsCOVID-19 was ascertained by an independent Event Committee until December 31, 2021. COX regression models compared the effect of PREDIMED-Plus interventions on COVID-19 risk. ResultsOverall, 653 COVID-19 incident cases were documented (IG:317; CG:336) over a median (IQR) follow-up of 5.8 (1.3) years (inclusive of 4.0 (1.2) years before community transmission of COVID-19) in both groups. A significantly lowered risk of COVID-19 incidence was not evident in IG, compared to CG (fully-adjusted HR (95% CI): 0.96 (0.81,1.12)). ConclusionsThere was no evidence to show that an intensive weight-loss intervention encouraging energy-reduced MedDiet and PA significantly lowered COVID-19 risk in older adults with overweight/ obesity and metabolic syndrome in comparison to ad libitum MedDiet. Recommendations to improve adherence to MedDiet provided with or without lifestyle modification suggestions for weight loss may have similar effects in protecting against COVID-19 risk in older adults with high cardiovascular risks.

Adherence to a Mediterranean diet may improve serum adiponectin in adults with nonalcoholic fatty liver disease: The MEDINA randomized controlled trial

Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% of adults worldwide, with chronic low-grade inflammation being a key pathophysiological feature of progression. The Mediterranean diet (MedDiet) is recognized for improving metabolic and hepatic outcomes in people with diabetes and NAFLD, in part, via anti-inflammatory properties. The aim of this study was to determine the effect of an ad libitum MedDiet versus low-fat diet (LFD) on inflammatory markers in adults with NAFLD. It was hypothesized that the MedDiet, and its individual components, would improve inflammation. This multicenter, randomized controlled trial, randomized participants to a MedDiet or LFD intervention for 12 weeks. Primary outcomes included change from baseline to 12 weeks for serum high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, adiponectin, leptin, and resistin. Forty-two participants (60% female; age 52.3 ± 12.6 years; body mass index, 32.2 ± 6.2 kg/m²) were randomized to the MedDiet (n=19) or low-fat diet (n=23). At 12 weeks, the LFD showed a greater decrease in leptin compared with the MedDiet (-1.20 ± 3.9 ng/mL vs 0.64 ± 3.5 ng/mL, P=.010). Adiponectin significantly improved within the MedDiet (13.7 ± 9.2 µg/mL to 17.0 ± 12.5 µg/mL, P=.016), but not within the LFD group. No statistically significant changes were observed for other inflammatory markers following the MedDiet or LFD. Adherence to the MedDiet significantly improved in both study arms, although greater improvements were seen in the MedDiet group. Adiponectin significantly improved following a Mediterranean diet intervention, in the absence of weight loss. The low-fat diet did not elicit improvements in inflammatory markers. High-quality clinical trials appropriately powered to inflammatory markers are required in this population.

Mediterranean diet and psychological well-being intervention to reverse metabolic syndrome in Chile (CHILEMED trial)

Psychosocial status and lifestyle are key risk factors of non-communicable diseases (NCDs), which, in turn, are main drivers of healthcare costs and morbimortality worldwide, including Chile. Mediterranean diet (MedDiet) is one of the healthiest dietary patterns under study. However, its impact on high-risk conditions, such as metabolic syndrome (MetS), and NCDs outside the Mediterranean Basin remains mostly unexplored. Even though Central Chile has an environment, food production, and culinary traditions comparable to those present in Mediterranean countries, few studies -some with significant methodological limitations- have evaluated the effect of MedDiet on health and/or disease in Chilean subjects. Importantly, a Mediterranean lifestyle is a modus vivendi that integrates physical health with mental and social well-being. Psychological well-being (PWB) is associated with healthy behaviors, positive health outcomes, and longevity, thereby emerging as a novel healthcare goal. We report here an ongoing randomized controlled clinical trial in Chilean patients with MetS seeking to test whether (1) a PWB theory-based intervention facilitates induction to and increases long-term adherence to a locally adapted MedDiet, and (2) a MedDiet intervention -implemented alone or combined with well-being promotion- is more effective at reversing MetS compared to individuals following a low-fat diet without psychological support. The CHILEan MEDiterranean (CHILEMED) diet intervention study is a 1-year trial including patients with MetS living in Chile. Participants will be assigned randomly by a computer-generated random number sequence to one of the three intervention arms: a) low-fat diet as control group, b) MedDiet alone, and c) MedDiet plus well-being support. Patients will be followed-up by individual and/or group online nutritional sessions or phone cal as well as 6- and 12-month in-person re-assessment of medical history, medication use, food intake, PWB, anthropometrics/physical exam, and blood collection for laboratory analysis. The primary outcome of the trial will be the effect of the MedDiet -with or without PWB intervention- on overall reversal of MetS compared to low-fat diet alone. Based on a statistical superiority trial, expected impact, and patient loss, the estimated study sample is 339 subjects (113 individuals per arm in 3 equal-sized groups). Currently, we have enrolled 179 patients, predominantly women, evenly distributed by age (group means ranging from 45.7 to 48,9 years-old), 3/4 are obese with almost all of them showing abdominal obesity, 70% are hypertensive, whereas <10% exhibit diabetes. If findings turn out as expected (e.g., MedDiet -with or without PWB intervention- is better than the low-fat diet for reversion of MetS at 1-year follow-up), CHILEMED will provide further beneficial evidence of the MedDiet on NCD risk conditions beyond the Mediterranean region.

Barriers and Facilitators to Adherence to a Mediterranean Diet Intervention during Chemotherapy Treatment: A Qualitative Analysis

Patients undergoing chemotherapy are at risk for malnutrition and a high symptom burden, and nutritional interventions can address clinical and supportive care outcomes. Herein, we identified barriers and facilitators to adhering to a Mediterranean Diet (MedDiet) intervention during chemotherapy. Patients with cancer (any type) who were undergoing chemotherapy were enrolled into a clinical trial testing the effects of an 8-week MedDiet intervention on cancer-related fatigue. Participants were randomized 2:1, MedDiet:control. The intervention entailed food provision, education, a cookbook, a session with a nutritionist, and weekly check-ins. Post-intervention, all participants completed semi-structured exit interviews. The interviews were transcribed and open coding was conducted to describe the facilitators and barriers to MedDiet adherence. Participants (n = 29, n = 21 in the intervention group) were 51.0 ± 15.1 years old and 93.1% had breast cancer. Educational materials and convenient food delivery were the highest reported facilitators. Many patients offered that changing their diet gave a sense of control and empowerment. Barriers to adherence were that the frozen food was unappetizing, participants’ (or their spouse/children’s) food preferences did not align with the MedDiet, and chemotherapy-induced side effects that prevented food consumption (eg, mouth sores, lack of appetite). This project helps understand the patient experience within nutritional interventions to optimize dietary programs during chemotherapy treatment.

The diet rapidly and differentially affects the gut microbiota and host lipid mediators in a healthy population

BackgroundBioactive lipids produced by human cells or by the gut microbiota might play an important role in health and disease. Dietary intakes are key determinants of the gut microbiota, its production of short-chain (SCFAs) and branched-chain fatty acids (BCFAs), and of the host endocannabinoidome signalling, which are all involved in metabolic diseases. This hypothesis-driven longitudinal fixed sequence nutritional study, realized in healthy participants, was designed to determine if a lead-in diet affects the host response to a short-term dietary intervention. Participants received a Mediterranean diet (MedDiet) for 3 days, a 13-day lead-in controlled diet reflecting the average Canadian dietary intake (CanDiet), and once again a MedDiet for 3 consecutive days. Fecal and blood samples were collected at the end of each dietary phase to evaluate alterations in gut microbiota composition and plasma levels of endocannabinoidome mediators, SCFAs, and BCFAs.ResultsWe observed an immediate and reversible modulation of plasma endocannabinoidome mediators, BCFAs, and some SCFAs in response to both diets. BCFAs were more strongly reduced by the MedDiet when the latter was preceded by the lead-in CanDiet. The gut microbiota response was also immediate, but not all changes due to the CanDiet were reversible following a short dietary MedDiet intervention. Higher initial microbiome diversity was associated with reduced microbiota modulation after short-term dietary interventions. We also observed that BCFAs and 2-monoacylglycerols had many, but distinct, correlations with gut microbiota composition. Several taxa modulated by dietary intervention were previously associated to metabolic disorders, warranting the need to control for recent diet in observational association studies.ConclusionsOur results indicate that lipid mediators involved in the communication between the gut microbiota and host metabolism exhibit a rapid response to dietary changes, which is also the case for some, but not all, microbiome taxa. The lead-in diet influenced the gut microbiome and BCFA, but not the endocannabinoidome, response to the MedDiet. A higher initial microbiome diversity favored the stability of the gut microbiota in response to dietary changes. This study highlights the importance of considering the previous diet in studies relating the gut microbiome with lipid signals involved in host metabolism.91qzVqRa16ptEbbFa4LH5iVideo

Effects of Supplemented Mediterranean Diets on Plasma-Phospholipid Fatty Acid Profiles and Risk of Cardiovascular Disease after 1 Year of Intervention in the PREDIMED Trial.

Plasma fatty acids (FAs) have been associated with cardiovascular disease (CVD) risk. Diet and endogenous metabolism influence the FA profile of the plasma phospholipid (PL) fraction. In the PREDIMED trial, we examined 1-year changes in the FA profile of plasma PL according to a nutritional intervention with Mediterranean diets, either supplemented with extra-virgin olive oil (MedDiet + EVOO) or mixed nuts (MedDiet + nuts), in a high cardiovascular risk population. We also analyzed if 1-year changes in PL FAs were associated with subsequent cardiovascular risk. We included 779 participants in our case-cohort study: 185 incident cases and 594 participants in the subcohort (including 31 overlapping cases). The end point was the incidence of CVD. We measured the FAs of plasma PL at baseline and after 1 year of intervention. MedDiet + EVOO increased C17:0 and C20:3n9 in linear regression models [β coefficientperSD : 0.215 (95% CI, 0.032-0.399) and 0.271 (0.107-0.434), respectively] and decreased 16:1n7 and C22:4n6 [βperSD: -0.239 (95% CI, -0.416 to -0.061) and -0.287 (95% CI, -0.460 to -0.113), respectively] vs the control group. MedDiet + nuts increased C18:3n3 [βperSD: 0.382 (95% CI, 0.225 - 0.539)], C18:2n6 [βper SD: 0.250 (95% CI, 0.073 - 0.428)], C18:0 [βperSD: 0.268 (95% CI, 0.085-0.452)], and C22:0 [βper SD: 0.216 (95% CI, 0.031-0.402)]; and decreased the sum of six n6 FAs [βper SD: -0.147 (95% CI, -0.268 to -0.027)] vs the control group. The 1-year increase in C18:2n6 was inversely associated with the subsequent CVD risk (HRperSD: 0.64 (95% CI, 0.44-0.92)). MedDiet interventions changed n6 FAs and C16:1n7c; other changes were specific for each group: MedDiet + EVOO increased C17:0 and C20:3n9, and MedDiet + Nuts C18:3n3, C18:2n6, C18:0, and C22:0 FAs.

Adherence to a Mediterranean Diet for 6 Months Improves the Dietary Inflammatory Index in a Western Population: Results from the MedLey Study.

Increasing evidence supports that a higher dietary inflammatory index (DII®) score is associated with inflammation and cardiovascular disease (CVD) risk, events, and mortality. This randomized trial sought to determine if a change to a Mediterranean diet resulted in a reduction in the DII score, and then it evaluated the relationship between the DII and cardiometabolic outcomes following the administration of a traditional Mediterranean diet in older Australian adults. A total of 152 Australian adults (mean age 71 ± 5 years) was randomly allocated either a MedDiet (n = 80) or to continue their habitual diet (HabDiet) (n = 72) for 6 months. Diet and cardiovascular outcomes were measured at baseline and 3 and 6 months of the intervention. DII and energy-adjusted DII (E-DIITM) scores were calculated from 3-day weighed food records. There was a significant reduction in the DII score at 2 and 4 months for the MedDiet group (−1.40 ± 0.20 p < 0.001 and −1.47 ± 0.20 p < 0.001, respectively), which was significantly different from the HabDiet group over time (p < 0.001). The HabDiet DII score did not change significantly at the 2 and 4 months timepoints (0.47 ± 0.21 p = 0.35 and 0.54 ± 0.21 p = 0.21, respectively). The improvement in the DII in the MedDiet group was not related to any cardiometabolic outcome. Baseline cross-sectional analyses identified a positive association between the E-DII score and average BMI, body weight, WHR, abdominal adiposity, and SBP, and a negative association with HDL-C. We demonstrate that a MedDiet intervention significantly reduced DII scores compared with a habitual Australian diet in older Australians. This could be beneficial for healthy ageing and the avoidance of chronic disease in Western populations.

Sex differences in endocannabinoids during 3 years of Mediterranean diet intervention: Association with insulin resistance and weight loss in a population with metabolic syndrome.

Excess circulating endocannabinoids (eCBs) and imbalanced N-acylethanolamines (NAEs) related eCBs abundance could influence dietary weight loss success. We aimed to examine sex differences in the impact of a 3-years Mediterranean diet (MedDiet) intervention on circulating eCBs, NAEs and their precursor fatty acids, and to analyze the interplay between changes in eCBs or NAEs ratios, insulin resistance and the achievement of clinically meaningful weight reductions. Prospective cohort study in a subsample of N = 105 participants (54.3% women; 65.6 ± 4.6 years) with overweight or obesity and metabolic syndrome that underwent a 3-years MedDiet intervention (PREDIMED-Plus study). Plasma eCBs and NAEs, including 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), fatty acids, diet, glycemic homeostasis (including the assessment of insulin resistance-HOMA-IR), and cardiovascular risk markers were monitored (at 0-6-12-36 months). Mediterranean diet adherence increased in both sexes and remained high during the 3 years of follow-up. Reductions in body weight, glycemic and cardiovascular parameters were larger in men than in women. Women presented higher concentrations of NAEs than men throughout the study. In both sexes, AEA and other NAEs (including OEA, and PEA) decreased after 6 months (for AEA: -4.9%), whereas the ratio OEA/AEA increased after 1 year (+5.8%). Changes in 2-AG (-3.9%) and the ratio OEA/PEA (+8.2%) persisted over the 3 years of follow-up. In women, 6-months changes in AEA (OR = 0.65) and the ratio OEA/AEA (OR = 3.28) were associated with the achievement of 8% weight reductions and correlated with HOMA-IR changes (r = 0.29 and r = -0.34). In men, OEA/PEA changes were associated with 8% weight reductions (OR = 2.62) and correlated with HOMA-IR changes (r = -0.32). A 3-years MedDiet intervention modulated plasma concentrations of eCBs and NAEs. Changes in AEA and in the relative abundance of NAEs were associated with clinically meaningful weight reductions. However, marked sex differences were identified in eCBs and NAEs, as well as in the efficacy of the intervention in terms of glycemic and cardiovascular parameters, which could be related to post-menopause alterations in glucose metabolism. These findings support a sex-balanced research strategy for a better understanding of the mechanisms underlying the regulation of body weight loss.

Mid- and long-term changes in satiety-related hormones, lipid and glucose metabolism, and inflammation after a Mediterranean diet intervention with the goal of losing weight: A randomized, clinical trial.

Obesity is produced by the enlargement of the adipose tissue. Functioning as an endocrine organ, it releases and receives information through a complex network of cytokines, hormones, and substrates contributing to a low-chronic inflammation environment. Diet and healthy habits play key roles in the prevention of obesity and its related pathologies. In this regard, there is a need to switch to healthier and more appetizing diets, such as the Mediterranean one. To compare the mid-and long-term effects of two Mediterranean diet (MedDiet) interventions, one energy-reduced plus physical activity promotion versus a non-restrictive diet, on peripheral satiety-related hormones, weight loss, glucose/lipid metabolism, and pro-inflammatory markers in subjects with obesity/overweight and metabolic syndrome. A randomized, lifestyle intervention was conducted in 23 Spanish centers, with a large cohort of patients presenting metabolic syndrome. Our study is a subproject set in IMIM (Hospital del Mar Research Institute). Participants were men and women, aged 55-75 and 60-75, respectively, who at baseline met at least three metabolic syndrome components. Subjects were assigned to two intervention groups: (1) an intensive lifestyle intervention with an energy-reduced MedDiet and physical activity promotion (intervention group) with the aim of weight loss; and (2) a normocaloric MedDiet (control). We quantified in a subsample of 300 volunteers from Hospital del Mar Research Institute (Barcelona), following analytes at baseline, 6 months, and 1 year: glucose, HbA1c, triglycerides, total cholesterol, high-density lipoprotein cholesterol, LDL cholesterol, C-peptide, ghrelin, GLP-1, glucagon, insulin, leptin, PAI-1, resistin, and visfatin. Anthropometric and classical cardiovascular risk factors were also determined. A multivariate statistical model was employed to compare the two groups. Linear mixed-effect models were performed to compare changes in risk factors and biomarkers between intervention groups and over time. Compared to participants in the control group, those in intervention one showed greater improvements in weight, waist circumference, insulin (P < 0.001), glucose metabolism-related compounds (P < 0.05), triglyceride-related lipid profile (P < 0.05), leptin, blood pressure, and pro-inflammatory markers such as PAI-1 (P < 0.001) at mid-and/or long-term. High-sensitivity C-reactive protein, resistin, and vifastin also decreased in both groups. A weight loss intervention employing a hypocaloric MedDiet and physical activity promotion has beneficial effects on adiposity, glucose metabolism, lipid profile, leptin, and pro-inflammatory markers, such as PAI-1 in both mid-and long-term.

Arginine catabolism metabolites and atrial fibrillation or heart failure risk: 2 case-control studies within the Prevención con Dieta Mediterránea (PREDIMED) trial

Arginine-derived metabolites are involved in oxidative and inflammatory processes related to endothelial functions and cardiovascular risks. We prospectively examined the associations of arginine catabolism metabolites with the risks of atrial fibrillation (AF) or heart failure (HF), and evaluated the potential modifications of these associations through Mediterranean diet (MedDiet) interventions in a large, primary-prevention trial. Two nested, matched, case-control studies were designed within the Prevención con Dieta Mediterránea (PREDIMED) trial. We selected 509 incident cases and 547 matched controls for the AF case-control study and 326 cases and 402 matched controls for the HF case-control study using incidence density sampling. Fasting blood samples were collected at baseline and arginine catabolism metabolites were measured using LC-tandem MS. Multivariable conditional logistic regression models were applied to test the associations between the metabolites and incident AF or HF. Interactions between metabolites and intervention groups (MedDiet groups compared with control group) were analyzed with the likelihood ratio test. Inverse association with incident AF was observed for arginine (OR per 1 SD, 0.83; 95% CI: 0.73-0.94), whereas a positive association was found for N1-acetylspermidine (OR for Q4 compared with Q1 1.58; 95% CI: 1.13-2.25). For HF, inverse associations were found for arginine (OR per 1 SD, 0.82; 95% CI: 0.69-0.97) and homoarginine (OR per 1 SD, 0.81; 95% CI: 0.68-0.96), and positive associations were found for the asymmetric dimethylarginine (ADMA) and symmetric dimethlyarginine (SDMA) ratio (OR per 1 SD, 1.19; 95% CI: 1.02-1.41), N1-acetylspermidine (OR per 1 SD, 1.34; 95% CI: 1.12-1.60), and diacetylspermine (OR per 1 SD, 1.20; 95% CI: 1.02-1.41). In the stratified analysis according to the dietary intervention, the lower HF risk associated with arginine was restricted to participants in the MedDiet groups (P-interaction = 0.044). Our results suggest that arginine catabolism metabolites could be involved in AF and HF. Interventions with the MedDiet may contribute to strengthen the inverse association between arginine and the risk of HF. This trial was registered at controlled-trials.com as ISRCTN35739639.

The Effects of a Mediterranean Diet Intervention on Cancer-Related Fatigue for Patients Undergoing Chemotherapy: A Pilot Randomized Controlled Trial.

Simple SummaryCancer-related fatigue affects the majority of people undergoing chemotherapy for cancer. The Mediterranean Diet provides healthy macro- and micronutrients that promote energy production and counter known mechanisms that contribute to fatigue. Thus, we designed a Mediterranean Diet program specifically for patients undergoing chemotherapy that included food provision, education, a cookbook, and weekly telephone check-ins. In a two-arm randomized controlled trial (n = 33), we found that our program was safe and feasible; there was excellent adherence (>70%) to the Mediterranean Diet. The Mediterranean Diet program led to less fatigue to a small-moderate degree at weeks 4 and 8. For those with a lower Mediterranean Diet score before the program, the program had a larger effect. Mitochondria are the cellular organelles that produce ATP energy and, in circulating T cells, fatigue was associated with mitochondrial dysfunction. These data support larger studies testing how and how much a Mediterranean Diet during chemotherapy can alleviate fatigue.Cancer-related fatigue is a common, burdensome symptom of cancer and a side-effect of chemotherapy. While a Mediterranean Diet (MedDiet) promotes energy metabolism and overall health, its effects on cancer-related fatigue remain unknown. In a randomized controlled trial, we evaluated a rigorous MedDiet intervention for feasibility and safety as well as preliminary effects on cancer-related fatigue and metabolism compared to usual care. Participants had stage I–III cancer and at least six weeks of chemotherapy scheduled. After baseline assessments, randomization occurred 2:1, MedDiet:usual care. Measures were collected at baseline, week 4, and week 8 including MedDiet adherence (score 0–14), dietary intake, and blood-based metabolic measures. Mitochondrial respiration from freshly isolated T cells was measured at baseline and four weeks. Participants (n = 33) were 51.0 ± 14.6 years old, 94% were female, and 91% were being treated for breast cancer. The study was feasible, with 100% completing the study and >70% increasing their MedDiet adherence at four and eight weeks compared to baseline. Overall, the MedDiet intervention vs. usual care had a small-moderate effect on change in fatigue at weeks 4 and 8 (ES = 0.31, 0.25, respectively). For those with a baseline MedDiet score <5 (n = 21), the MedDiet intervention had a moderate-large effect of 0.67 and 0.48 at weeks 4 and 8, respectively. The MedDiet did not affect blood-based lipids, though it had a beneficial effect on fructosamine (ES = −0.55). Fatigue was associated with mitochondrial dysfunction including lower basal respiration, maximal respiration, and spare capacity (p < 0.05 for FACIT-F fatigue subscale and BFI, usual fatigue). In conclusion, the MedDiet was feasible and attenuated cancer-related fatigue among patients undergoing chemotherapy, especially those with lower MedDiet scores at baseline.

Development of a Remote Mediterranean Diet Intervention for Patients With Cancer During Chemotherapy Treatment: A Mixed Methods Analysis

ObjectivesThe Mediterranean Diet (MedDiet) is rich in fruit, vegetables, whole grains, and bioactive compounds. Despite emerging research on the benefits of nutrition to complement the efficacy of chemotherapy and reduce symptom burden, there are few structured nutritional programs available for patients with cancer. Herein, we developed a MedDiet intervention for patients undergoing chemotherapy and identified barriers and facilitators to adherence. MethodsThis was a qualitative analysis of the intervention arm of a randomized controlled trial (NCT04534738). Participants were eligible if they had cancer (any type) and had at least 6 weeks of chemotherapy scheduled. The 8-week MedDiet intervention included home food delivery (frozen meals and MedDiet ingredients for the first 4 weeks), education, goal-setting, a cookbook, and weekly phone calls with a nutritionist. MedDiet adherence was measured using the MedDiet Adherence questionnaire at baseline, 4 weeks, and 8 weeks; change from baseline was assessed using paired t-tests at 4 and 8 weeks. After completion of the study, participants underwent a semi-structured interview to provide feedback on the program. Interviews were transcribed and themes were identified using emergent coding. ResultsParticipants (n = 23) were 52.5 ± 13.6 years old, 91% female, and 83% White. Participants had breast (87%) or another type of cancer. MedDiet adherence score increased from 4.0 ± 2.7 at baseline to 6.7 ± 2.8 at 4 weeks and 6.5 ± 2.6 at 8 weeks (both p < 0.001). Interviews were conducted with 21 patients. While most participants (n = 15, 71%) did not actively seek nutritional information before treatment, most (n = 19, 90%) were highly engaged with the MedDiet program. Many (n = 11) volunteered feelings of empowerment and/or a welcomed a sense of control. Facilitators to adherence included accountability, structure, provision of food, palatability, and easy adoption. Barriers included chemotherapy-induced taste changes and mouth sores, others preparing food for the patient, cooking for family members’ preferences, and mental burden. ConclusionsA remote MedDiet intervention was effective and well received by patients undergoing chemotherapy. Future research should investigate how a MedDiet intervention affects clinical outcomes and symptom burden. Funding SourcesNIH National Cancer Institute.

Development of a remote Mediterranean Diet intervention during chemotherapy treatment: A qualitative analysis.

e24033 Background: The Mediterranean Diet (MedDiet) has emerged as an effective health-promoting dietary pattern. It is high in fruit, vegetables, whole grains, fiber, antioxidants, and anti-inflammatory compounds. A cancer diagnosis is often seen as a “window of opportunity” for behavior change, yet there are few structured nutritional programs available for patients undergoing active treatment. Herein, we developed a remote MedDiet intervention and identified barriers and facilitators to adherence. Methods: This was a qualitative analysis of the intervention arm of a clinical trial (NCT04534738). Participants had at least 6 weeks of chemotherapy scheduled. The MedDiet intervention was 8 weeks and included home food delivery (frozen meals and fresh ingredients weekly for the first 4 weeks), education, goal-setting, a cookbook, and weekly phone calls with a nutritionist. MedDiet adherence was measured using the MedDiet Adherence questionnaire at baseline, 4 weeks, and 8 weeks; change was assessed using paired t-tests between baseline and 4 and 8 weeks. After the study, participants underwent a semi-structured interview to provide feedback on the intervention. Interviews were transcribed and emergent coding was used to identify themes. Results: Patients (n = 23) were 52.5±13.6 years old, 2 were male, 83% were White, and 87% had breast cancer. MedDiet adherence was 4.0±2.7 at baseline. It increased 2.1±3.2 points from baseline to 4 weeks and 2.5±3.0 from baseline to 8 weeks (both p &lt; 0.001). Interviews were conducted with 21 patients (example quotes in Table). Although most participants (n = 15, 71%) did not seek nutritional information at the time of their diagnosis, most (n = 19, 90%) were highly engaged with the program. In response to an open-ended question, many (n = 11) expressed a sense of empowerment. Facilitators to adherence included structure, accountability, food provision, palatability, and easy procurement of ingredients. Barriers included chemotherapy-induced taste changes and mouth sores, cooking for family members’ preferences, others preparing food for the patient, and higher priority areas for mental energy expenditure. The majority (n = 13, 62%) preferred a program during vs. after cancer treatment. All (21/21) indicated they would continue to follow at least some aspects of the diet. Conclusions: A remote MedDiet intervention was effective and well received by patients undergoing chemotherapy. Future research should investigate how a MedDiet intervention affects clinical outcomes and symptom burden. Clinical trial information: NCT04534738. [Table: see text]

The Effect of a Mediterranean Diet With or Without Calorie Restriction on Cognition, Lifestyle, and Metabolic Health of Obese, Predominately Non-Hispanic Black Older Adults

ObjectivesTo compare the effect of a Mediterranean Diet with (Med-WL) or without caloric restriction (Med-A) for intentional weight loss (IWL) versus a typical diet control (TDC) on cognition, lifestyle and cardiometabolic health.MethodsA randomized clinical trial of obese, predominately non-Hispanic black, older adults was conducted between June 2017 and December 2020 at community sites in Chicago, Illinois. Participants (n = 185) were randomized (2:2:1) to 1 of 3 groups for 8-months: Med-WL, Med-A, or TDC. The primary outcome was change from baseline to post-intervention in three cognitive composite scores: attention, information & processing; executive function; and learning, memory & recognition. Secondary outcomes included changes in MedDiet adherence, physical activity, body weight, total and regional body fat, blood pressure, fasting blood lipids, glucose, insulin and C-reactive protein (CRP).ResultsParticipants were 85.9% female with a mean (SD) age of 66.3 (6.1) years, and retention was similar across arms (85.3% Med-WL, 87.7% Med-A, 94.6% TDC, p = 0.36). The MedDiet interventions did not affect cognitive composite scores. MedDiet adherence improved significantly more in Med-WL (adjusted mean [95% CI] score change, +6.3 [4.9 to 7.6] points) and Med-A (+4.8 [3.4 to 6.2] points) relative to TDC (+0.6 [−1.3 to 2.4] points, p < 0.05). Weight loss was significantly greater in Med-WL (adjusted mean [95% CI]: −4.6 [(-5.6 to −3.5] kg) than in Med-A (-2.6 [−3.7 to −1.5] kg, p < 0.05) and TDC (−0.6 [−2.1 to 0.8] kg, p < 0.05). Reduction in central body fat was significantly greater in the MedDiet arms (adjusted mean change [95% CI], Med-WL: −147 [−235 to −59] gm; Med-A: −162 [−248 to −76] gm) than in TDC (+91 [−18 to 200] gm, p < 0.05). For cardiometabolic health, only fasting insulin changed significantly in Med-WL (adjusted mean change [95% CI]: −2.2 [−3.2 to −1.2] uIU/mL) relative to Med-A (−0.6 [−1.6 to 0.4] uIU/mL, p < 0.05) and TDC (−0.5 [−1.8 to 0.8] uIU/mL, p < 0.05).ConclusionsAn 8-month MedDiet lifestyle intervention with or without caloric restriction for IWL did not produce superior effects on cognitive function compared to a TDC, but it did produce significant effects on diet quality, total body weight and central body fat.Funding SourcesNational Heart, Lung And Blood Institute; National Cancer Institute; National Institute On Minority Health And Health Disparities.

A randomised controlled trial of a Mediterranean Dietary Intervention for Adults with Rheumatoid Arthritis (MEDRA): Study protocol

BackgroundRheumatoid arthritis (RA) is the most common type of autoimmune arthritis affecting 0.5–1% of the adult population worldwide. While the primary line of treatment of RA includes pharmacological therapies, people living with the condition often seek non-pharmacological therapies such as diet and exercise in an attempt to attenuate their symptoms. Established, evidence-based dietary guidelines for RA are currently lacking. The MEDRA study aims to explore the effectiveness of implementing, via telehealth, a Mediterranean type diet (MedDiet) compared to a standard healthy diet as per the Healthy Eating Guidelines (HEG) in Ireland in terms of differences in physical function and quality of life in adults with RA living in Ireland. MethodsThe MEDRA study is a parallel, randomised controlled trial delivered through telehealth methods. Forty-four eligible participants who have RA will be randomly allocated to either a MedDiet or HEG group for a 12 weeks intervention period. Primary outcome measures include changes in physical function and quality of life, both of which will be measured using validated questionnaires at baseline, six and twelve weeks. Both intervention arms will attend a total five teleconsultations with a Registered Dietitian (RD). The MedDiet intervention arm focuses on recommendations from the traditional Mediterranean diet and HEG intervention arm will use the dietary recommendations as currently advised in Ireland. DiscussionThis study will provide evidence as to whether dietary treatment of RA can improve physical function and quality of life in a small cohort of participants with RA. The results of the study will be disseminated at national scientific conferences and published in peer-reviewed journals. EthicsThis protocol has been approved by the Education and Health Sciences Research Ethics Committee at the University of Limerick (2020_09_05_EHS) and by the Health Service Executive Mid-Western Regional Hospital Research Ethics Committee (REC Ref 103/19). Trial registrationClinicalTrials.gov NCT04262505. Trial registration date: April 2, 2020.

Efficacy, Feasibility and Acceptability of a Mediterranean Diet Intervention on Hormonal, Metabolic and Anthropometric Measures in Overweight and Obese Women with Polycystic Ovary Syndrome: Study Protocol.

Polycystic ovary syndrome (PCOS) is a common endocrine condition in reproductive-aged women associated with metabolic, reproductive and psychological features. Lifestyle modification (diet/physical activity) is considered first-line treatment for PCOS. However, there is limited high-quality evidence to support therapeutic dietary interventions for PCOS beyond general population-based healthy eating guidelines. Adherence to a Mediterranean diet (MedDiet), with or without energy restriction, improves cardiometabolic health in populations including persons with or at high risk of cardiovascular disease and type 2 diabetes. However, there is limited research examining the MedDiet in PCOS. Therefore, this 12 week randomized controlled trial will investigate the efficacy of a MedDiet on cardiometabolic and hormonal parameters and explore its acceptability and feasibility in PCOS. Forty-two overweight and obese women with PCOS (aged 18–45 years) will be randomized to receive dietary advice consistent with Australian Dietary Guidelines or an ad libitum MedDiet intervention. All participants will receive fortnightly counselling to facilitate behaviour change. The primary outcomes will be changes in insulin resistance, glucose, total testosterone and sex hormone-binding globulin. Secondary outcomes include changes in body weight and feasibility and acceptability of the MedDiet intervention. The results of this study will provide further evidence on specific dietary approaches for management of PCOS.