New findings in the metabolism of the saffron apocarotenoids, crocins and crocetin, by the human gut microbiota.

The main constituents of saffron are the apocarotenoids crocins and crocetin, present in the stigmas. Numerous healthy properties, especially those related to the effects on the central nervous system, have been attributed to these compounds but the metabolites responsible for these effects are still unknown. Previous evidences in animal models suggest a role for the gut microbiota in the pharmacokinetics and the neuroprotective effects of these compounds. However, the interaction between these apocarotenoids and the gut microbiota has been poorly studied. In this article, we have thoroughly investigated the batch fermentation of crocin-1 and crocetin (10 µM) with human fecal samples of two donors at different incubation times (0-240 h) using a metabolomic approach. We corroborated a rapid transformation of crocin-1 which looses the glucose molecules through de-glycosylation reactions until its complete transformation into crocetin in 6 hours. A group of intermediate crocins with different degrees of glycosylation were detected in a very short time. Crocetin was further metabolized and new microbial metabolites produced by double-bond reduction and demethylation reactions were identified for the first time: dihydro and tetrahydro crocetins and di-demethyl crocetin. In addition, we detected changes in the levels of the short chain fatty acids valeric acid and hexanoic acid suggesting further structural modifications of crocetin or changes in the catabolic production of these compounds. This research is a pioneering study of the action of the human gut microbiota on the saffron apocarotenoids and goes one step further towards the discovery of metabolites potentially involved in the benefits of saffron.

Exploring the Relationship between Mediterranean Diet Adherence and Subjective Well-Being among Greek and Cypriot Adults.

Associations between subjective well-being (SWB) and dietary habits, employment status, and habitual activities are increasingly capturing the focus of researchers as well as policymakers worldwide. This study aimed to explore these associations in a sample of the population in Greece and Cyprus via an online survey. In total, 936 questionnaires (470: Cyprus, 466: Greece) were analyzed to study the associations between the Mediterranean Diet (MD) (using the 14-item MEDAS score, (14-MEDAS)), subjective well-being (SWB), and several socioeconomic factors. Key remarks of this survey highlight the positive impact of MD adherence on some well-being items. Namely, statistically significant differences were found on the following items: Satisfied with life (p < 0.001), Life worthwhile (p < 0.001), Feeling happy (p < 0.001), worried (p = 0.005), and depressed (p = 0.001), when comparing Low MD adherence (14-MEDAS < 5) to High MD adherence (14-MEDAS > 10). Other lifestyle habits such as spending time with friends and family, spending time in nature, and habitual physical activity were associated with aspects of SWB such as Life satisfaction, Life worthwhile, Feeling happy, and energetic. The findings support adherence to the MD, since it is associated with higher life satisfaction and self-reported happiness in this sample and should be considered when developing health policies on well-being.

Characterizing Factors Associated with Excess Body Weight: A Descriptive Study Using Principal Component Analysis in a Population with Overweight and Obesity.

Obesity is a worldwide epidemic, making it crucial to understand how it can be effectively prevented/treated. Considering that obesity is a multifactorial condition, this article carried out a baseline cross-sectional study of the variables involved in the disorder. Eighty-four subjects with overweight/obesity were recruited. Dietary baseline information was obtained by analysing three 24 h recalls. Resting metabolic rate was measured using indirect calorimetry, physical activity was measured through accelerometry, cardiometabolic parameters were determined in blood samples and body composition via anthropometry and bioimpedance. A univariant and multivariate exploratory approach was carried out using principal component analysis (PCA). Large inter-individual variability was observed in dietetic, biochemical, and physical activity measurements (coefficient of variation ≥ 30%), but body composition was more uniform. Volunteers had an unbalanced diet and low levels of physical activity. PCA reduced the 26 analysed variables to 4 factors, accounting for 65.4% of the total data variance. The main factor was the "dietetic factor", responsible for 24.0% of the total variance and mainly related to energy intake, lipids, and saturated fatty acids. The second was the "cardiometabolic factor" (explaining 16.8% of the variability), the third was the "adiposity factor" (15.2%), and the last was the "serum cholesterol factor" (9.4%).

Association between Mediterranean lifestyle and perception of well-being and distress in a sample population of university Italian students.

We investigated the extent to which adherence to the Mediterranean diet (MD) in combination with Mediterranean lifestyle factors influenced students' perceptions of subjective well-being (SWB) and distress. 939 undergraduates completed a survey to assess sociodemographic and lifestyle characteristics, including adherence to the MD, depression, anxiety, stress, and SWB. Data were analysed with correlation, logistic, and multiple linear regression models. Higher adherence to MD correlated with better SWB. Fruit, red meat, sweet and caffeinated beverages contributed significantly. However, it was the combination of adherence to MD with other factors, including quality of social relationships, income, smoking, sleep, and physical activity that better predicted SWB. Our results confirm the positive influence of MD on SWB. However, they also suggest the need to consider perceptions of well-being by a more holistic approach that considers physical and social factors simultaneously to improve the development of more effective educational and motivational programmes.

Saffron against Neuro-Cognitive Disorders: An Overview of Its Main Bioactive Compounds, Their Metabolic Fate and Potential Mechanisms of Neurological Protection.

Saffron (Crocus sativus L.) is a spice used worldwide as a colouring and flavouring agent. Saffron is also a source of multiple bioactive constituents with potential health benefits. Notably, saffron displays consistent beneficial effects against a range of human neurological disorders (depression, anxiety, sleeping alterations). However, the specific compounds and biological mechanisms by which this protection may be achieved have not yet been elucidated. In this review, we have gathered the most updated evidence of the neurological benefits of saffron, as well as the current knowledge on the main saffron constituents, their bioavailability and the potential biological routes and postulated mechanisms by which the beneficial protective effect may occur. Our aim was to provide an overview of the neuroprotective effects attributed to this product and its main bioactive compounds and to highlight the main research gaps that need to be further pursued to achieve full evidence and understanding of the benefits of saffron. Overall, improved clinical trials and adequately designed pre-clinical studies are needed to support the evidence of saffron and of its main bioactive components (e.g., crocin, crocetin) as a therapeutic product to combat neurological disorders.

Updated Information of the Effects of (Poly)phenols against Type-2 Diabetes Mellitus in Humans: Reinforcing the Recommendations for Future Research.

(Poly)phenols have anti-diabetic properties that are mediated through the regulation of the main biomarkers associated with type 2 diabetes mellitus (T2DM) (fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), insulin resistance (IR)), as well as the modulation of other metabolic, inflammatory and oxidative stress pathways. A wide range of human and pre-clinical studies supports these effects for different plant products containing mixed (poly)phenols (e.g., berries, cocoa, tea) and for some single compounds (e.g., resveratrol). We went through some of the latest human intervention trials and pre-clinical studies looking at (poly)phenols against T2DM to update the current evidence and to examine the progress in this field to achieve consistent proof of the anti-diabetic benefits of these compounds. Overall, the reported effects remain small and highly variable, and the accumulated data are still limited and contradictory, as shown by recent meta-analyses. We found newly published studies with better experimental strategies, but there were also examples of studies that still need to be improved. Herein, we highlight some of the main aspects that still need to be considered in future studies and reinforce the messages that need to be taken on board to achieve consistent evidence of the anti-diabetic effects of (poly)phenols.

An Exploratory Critical Review on TNF-α as a Potential Inflammatory Biomarker Responsive to Dietary Intervention with Bioactive Foods and Derived Products.

This review collects and critically examines data on the levels of tumour necrosis factor-alpha (TNF-α) in lean, overweight and obese subjects, and the effects of intervention with different foods and food products containing bioactive constituents in overweight/obese individuals. We additionally explore the influence of different single nucleotide polymorphisms (SNPs) on TNF-α levels and compare the response to food products with that to some anti-obesity drugs. Our aim was to provide an overview of the variability, consistency, and magnitude of the reported effects of dietary factors on TNF-α, and to envisage the reliability of measuring changes in the levels of this cytokine as a biomarker responsive to food intervention in association with the reduction in body weight. Regarding the circulating levels of TNF-α, we report: (i) a large intra-group variability, with most coefficients of variation (CV%) values being ≥30% and, in many cases, >100%; (ii) a large between-studies variability, with baseline TNF-α values ranging from <1.0 up to several hundred pg/mL; (iii) highly variable effects of the different dietary approaches with both statistically significant and not significant decreases or increases of the protein, and the absolute effect size varying from <0.1 pg/mL up to ≈50 pg/mL. Within this scenario of variability, it was not possible to discern clear differentiating limits in TNF-α between lean, overweight, and obese individuals or a distinct downregulatory effect on this cytokine by any of the different dietary approaches reviewed, i.e., polyunsaturated fatty acids (PUFAs), Vitamin-D (VitD), mixed (micro)nutrients, (poly)phenols or other phytochemicals. Further, there was not a clear relationship between the TNF-α responses and body weight changes. We found similarities between dietary and pharmacological treatments in terms of variability and limited evidence of the TNF-α response. Different factors that contribute to this variability are discussed and some specific recommendations are proposed to reinforce the need to improve future studies looking at this cytokine as a potential biomarker of response to dietary approaches.

Assessment of Subjective Well-Being in a Cohort of University Students and Staff Members: Association with Physical Activity and Outdoor Leisure Time during the COVID-19 Pandemic.

Time spent outdoors and physical activity (PA) promote mental health. To confirm this relationship in the aftermath of COVID-19 lockdowns, we explored individual levels of anxiety, depression, stress and subjective well-being (SWB) in a cohort of academic students and staff members and tested their association with sport practice, PA at leisure time and time spent outdoors. Our cross-sectional study collected data during the COVID-19 outbreak (April−May 2021) on 939 students and on 238 employees, who completed an online survey on sociodemographic and lifestyle features, depression, anxiety, stress, and SWB. Results showed that the students exhibited higher levels of anxiety, depression, and stress, and lower levels of SWB (p < 0.001 for all domains) compared to the staff members. Correlation analysis confirmed that PA and time spent in nature were associated to high mental health scores among staff and, more consistently, among students. Finally, mediation analyses indicated that the time spent in nature, social relationships, and levels of energy play a mediator role in the relationship between sport practice and SWB. Our evidence reinforces the protective role of time spent in nature in improving mental health, and provides support for policymakers to make appropriate choices for a better management of COVID-19 pandemic consequences.

A Systematic Review of the Cardiometabolic Benefits of Plant Products Containing Mixed Phenolics and Polyphenols in Postmenopausal Women: Insufficient Evidence for Recommendations to This Specific Population.

Menopause is characterized by endocrine and physiological changes and is often accompanied by increased body weight and cholesterol, glucose intolerance, and/or hypertension. These alterations are associated with increased risk for cardiovascular diseases (CVDs) and Type II diabetes mellitus (T2DM) that may be moderate by dietary plant phenolic compounds. In this review, we examine the current evidence of the impact of a variety of plant products (foods, extracts, beverages) rich in a mixture of phenolics and polyphenols on: (i) glucose and insulin levels; (ii) lipid profile; (iii) blood pressure; and (iv) biomarkers of inflammation and oxidative stress in postmenopausal women. We critically evaluate both the results of a range of intervention studies conducted in this specific subpopulation and the level of evidence supporting the benefits of consuming those products after the menopause. Overall, the current available evidence does not allow for specific dietary recommendations of these plant products rich in phenolics and polyphenols in this high-risk subpopulation. Our data show rather variable and small effects of the different products examined on the cardiometabolic biomarkers and further support the need to: (1) improve the quality of the study designs and data reporting; and (2) understand the variability in the response of the different biomarkers and establish clear differences between healthy and cardiometabolic disease levels.

Persistent Moderate-to-Weak Mediterranean Diet Adherence and Low Scoring for Plant-Based Foods across Several Southern European Countries: Are We Overlooking the Mediterranean Diet Recommendations?

The Mediterranean diet (MD) has been sponsored worldwide as a healthy and sustainable diet. Our aim was to update and compare MD adherence and food choices across several Southern European countries: Spain (SP), Portugal (PT), Italy (IT), Greece (GR), and Cyprus (CY) (MED, Mediterranean), and Bulgaria (BG) and the Republic of North Macedonia (NMK) (non-MED, non-Mediterranean). Participants (N = 3145, ≥18 y) completed a survey (MeDiWeB) with sociodemographic, anthropometric, and food questions (14-item Mediterranean Diet Adherence Screener, 14-MEDAS). The MED and non-MED populations showed moderate (7.08 ± 1.96) and weak (5.58 ± 1.82) MD adherence, respectively, with significant yet small differences across countries (SP > PT > GR > IT > CY > BG > NMK, p-value < 0.001). The MED participants scored higher than the non-MED ones for most of the Mediterranean-typical foods, with the greatest differences found for olive oil (OO) and white meat preference. In most countries, ≥70% of the participants reported quantities of red meat, butter, sweet drinks, and desserts below the recommended cutoff points, whereas <50% achieved the targets for plant-based foods, OO, fish, and wine. Being a woman and increasing age were associated with superior adherence (p-value < 0.001), but differences were rather small. Our results suggest that the campaigns carried out to support and reinforce the MD and to promote plant-based foods have limited success across Southern Europe, and that more hard-hitting strategies are needed.

Mediterranean Diet Adherence and Subjective Well-Being in a Sample of Portuguese Adults.

The Mediterranean diet (MD) and other lifestyle characteristics have been associated with well-being, a broad multiparameter concept that includes individual's subjective assessment of their own well-being (SWB). Some studies have suggested that diet influences SWB, thus, this work aimed to add novel information on the association of MD and SWB in a sample of Portuguese adults. Data on sociodemographic, economic, lifestyle, diet, and SWB were collected through a self-filled online questionnaire. MD adherence was assessed by the Mediterranean Diet Adherence Screener (MEDAS) score ]. Results showed a moderate adherence to the MD in 490 Portuguese adults (mean MEDAS of 7.4 ± 2.1). A higher MD adherence was found to be significantly positively associated with women, employed individuals, a higher number of meals per day, and those with frequent contact with nature (p-value < 0.0025, using Bonferroni adjustment). As a novelty, this study divided the participants into low SWB, medium SWB, and medium to high SWB profiles (3.9 ± 1.0; 6.2 ± 1.0; 8.2 ± 1.3, respectively; p-value < 0.05), which reported significantly increasing MEDAS scores (6.5 ± 2.1; 7.3 ± 2.1; 7.8 ± 1.9; respectively, p-value < 0.05).

Exploring the Validity of the 14-Item Mediterranean Diet Adherence Screener (MEDAS): A Cross-National Study in Seven European Countries around the Mediterranean Region.

This study provides comprehensive validation of the 14-item Mediterranean Diet Adherence Screener (14-MEDAS) in an adult population from Greece (GR), Portugal (PT), Italy (IT), Spain (SP), Cyprus (CY), Republic of North Macedonia (NMK), and Bulgaria (BG). A moderate association between the 14-MEDAS and the reference food diary was estimated for the entire population (Pearson r = 0.573, p-value < 0.001; Intraclass Correlation Coefficient (ICC) = 0.692, p-value < 0.001) with the strongest correlation found in GR, followed by PT, IT, SP, and CY. These results were supported by kappa statistics in GR, PT, IT, and SP with ≥50% of food items exhibiting a fair or better agreement. Bland-Altman analyses showed an overestimation of the 14-MEDAS score in the whole population (0.79 ± 1.81, 95%Confidence Interval (CI) 0.61, 0.96), but this value was variable across countries, with GR, NMK, and BG exhibiting the lowest bias. Taking all analyses together, the validation achieved slightly better results in the Mediterranean countries but a definitive validation ranking order was not evident. Considering growing evidence of the shift from Mediterranean Diet (MD) adherence and of the importance of culture in making food choices it is crucial that we further improve validation protocols with specific applications to compare MD adherence across countries.

Why interindividual variation in response to consumption of plant food bioactives matters for future personalised nutrition.

Food phytochemicals are increasingly considered to play a key role in the cardiometabolic health effects of plant foods. However, the heterogeneity in responsiveness to their intake frequently observed in clinical trials can hinder the beneficial effects of these compounds in specific subpopulations. A range of factors, including genetic background, gut microbiota, age, sex and health status, could be involved in these interindividual variations; however, the current knowledge is limited and fragmented. The European network, European Cooperation in Science and Technology (COST)-POSITIVe, has analysed, in a systematic way, existing knowledge with the aim to better understand the factors responsible for the interindividual variation in response to the consumption of the major families of plant food bioactives, regarding their bioavailability and bioefficacy. If differences in bioavailability, likely reflecting differences in human subjects' genetics or in gut microbiota composition and functionality, are believed to underpin much of the interindividual variability, the key molecular determinants or microbial species remain to be identified. The systematic analysis of published studies conducted to assess the interindividual variation in biomarkers of cardiometabolic risk suggested some factors (such as adiposity and health status) as involved in between-subject variation. However, the contribution of these factors is not demonstrated consistently across the different compounds and biological outcomes and would deserve further investigations. The findings of the network clearly highlight that the human subjects' intervention studies published so far are not adequate to investigate the relevant determinants of the absorption/metabolism and biological responsiveness. They also emphasise the need for a new generation of intervention studies designed to capture this interindividual variation.

Combined effect of interventions with pure or enriched mixtures of (poly)phenols and anti-diabetic medication in type 2 diabetes management: a meta-analysis of randomized controlled human trials.

PURPOSE: (Poly)phenols have been reported to confer protective effects against type 2 diabetes but the precise association remains elusive. This meta-analysis aimed to assess the effects of (poly)phenol intake on well-established biomarkers in people with type 2 diabetes or at risk of developing diabetes. METHODS: A systematic search was conducted using the following selection criteria: (1) human randomized controlled trials involving individuals with prediabetes and type 2 diabetes; (2) one or more of the following biomarkers: glucose, glycated haemoglobin (HbA1c), insulin, pro-insulin, homeostatic model assessment of insulin resistance (HOMA-IR), islet amyloid polypeptide (IAPP)/amylin, pro-IAPP/pro-amylin, glucagon, C-peptide; (3) chronic intervention with pure or enriched mixtures of (poly)phenols. From 488 references, 88 were assessed for eligibility; data were extracted from 27 studies and 20 were used for meta-analysis. The groups included in the meta-analysis were: (poly)phenol mixtures, isoflavones, flavanols, anthocyanins and resveratrol. RESULTS: Estimated intervention/control mean differences evidenced that, overall, the consumption of (poly)phenols contributed to reduced fasting glucose levels (- 3.32 mg/dL; 95% CI - 5.86, - 0.77; P = 0.011). Hb1Ac was only slightly reduced (- 0.24%; 95% CI - 0.43, - 0.044; P = 0.016) whereas the levels of insulin and HOMA-IR were not altered. Subgroup comparative analyses indicated a stronger effect on blood glucose in individuals with diabetes (- 5.86 mg/dL, 95% CI - 11.34, - 0.39; P = 0.036) and this effect was even stronger in individuals taking anti-diabetic medication (- 10.17 mg/dL, 95% CI - 16.59, - 3.75; P = 0.002). CONCLUSIONS: Our results support that the consumption of (poly)phenols may contribute to lower glucose levels in individuals with type 2 diabetes or at risk of diabetes and that these compounds may also act in combination with anti-diabetic drugs.

Polyphenol-Rich Foods for Human Health and Disease.

Polyphenols are a class of well-known bioactive compounds widely distributed in the plant kingdom and abundant in plant foods and derived food products [...].

The inhibitory effect of flavonoids and their gut-derived metabolites on the replication of Chlamydia abortus in the AH-1 ovine trophoblast cell line.

The obligate intracellular bacterium Chlamydia abortus causes abortion and constitutes a worldwide threat for livestock. Plant-derived flavonoids have antimicrobial effects against veterinary and human pathogens and may be of help in the fight against C. abortus. The anti-infective efficacy against C. abortus of the flavonoids apigenin and naringenin, and of four of their derived metabolites was explored using an in vitro model of ovine trophoblast cells. Overall, the anti-infective effectiveness was apigenin > naringenin > benzoic acid > 3-(4-hydroxyphenyl) propionic acid ~ 4-hydroxyphenyl acetic acid ~ 4-hydroxybenzoic. At the lowest concentration tested (10 µM), apigenin, naringenin and benzoic acid inhibited the formation of C. abortus inclusions by 80%, 67%, and 39%, respectively. The cytotoxicity and anti-proliferative effects on the trophoblast host cells also differed greatly between the tested compounds. Our findings suggest that flavonoids may be of therapeutic value against C. abortus infection but metabolic conversion has a substantial and variable effect on their anti-chlamydial activity. Our results also support the notion that the mechanisms of anti-infective action may involve combined effects of the compounds against the host cells and the bacteria.

Chokeberry Juice Containing Polyphenols Does Not Affect Cholesterol or Blood Pressure but Modifies the Composition of Plasma Phospholipids Fatty Acids in Individuals at Cardiovascular Risk.

Chokeberry polyphenols have been suggested to reduce cholesterol and blood pressure and thus protect against cardiovascular diseases (CVD), but the evidence in humans is limited and inconsistent. This randomized double-blinded three-parallel groups trial investigated the changes in various anthropometric and clinical biomarkers, and in plasma phospholipids fatty acids (PPFA) in volunteers at cardiovascular risk after a four-week intervention with 100 mL/day of (1) chokeberry juice with a high-dose of polyphenols (1177.11 mg gallic acid equivalents, GAE); (2) chokeberry juice with a low-dose of polyphenols (294.28 mg GAE) and; (3) a nutritionally matched polyphenol-free placebo drink. Our results indicate that the intake of chokeberry juice containing either the low or the high dose of polyphenols cannot be linked with a reduction in total- and low-density lipoprotein (LDL)cholesterol or in systolic (SBP) and diastolic (DBP) blood pressure in comparison with the consumption of the placebo drink. However, we found evidence of moderate changes in the PPFA, i.e., increased saturated fatty acids (SFA), mostly palmitic acid, and reduced n-6 polyunsaturated fatty acids (PUFA), principally linoleic acid (LA) with the intake of chokeberry against the placebo. These effects may be associated with the polyphenols but we could not differentiate a clear dose-response effect. Further research is still needed to elucidate the contribution of the polyphenolic fraction to the potential cardiovascular effects of the chokeberry and to build up the evidence of its potential benefit via the modulation of PPFA composition.

An Exploratory Search for Potential Molecular Targets Responsive to the Probiotic Lactobacillus salivarius PS2 in Women With Mastitis: Gene Expression Profiling vs. Interindividual Variability.

Probiotics constitute an attractive alternative in the battle against microbial infections. Oral administration of certain strains of lactobacilli isolated from human milk has resulted in an effective reduction of the bacterial load as well as an improvement of the mastitis-associated symptoms. Nevertheless, little is yet known about the potential molecular mechanisms and specific targets implicated in these effects. Transcriptomic profiling has been used to search for disease-associated and therapy-responsive molecules in different disorders and experimental models. We have applied for the first time a gene expression-based molecular approach to explore for potential targets responsive to intervention with a probiotic in: (i) breast milk somatic cells (n = 17) and (ii) blood leukocytes (n = 19). Women with mastitis ingested a new strain of lactobacilli, Lactobacillus salivarius PS2 (3 × capsules per day, each capsule contained ~9.5 log10 CFU) for 21 days. We applied Affymetrix microarrays and Taqman one-step quantitative reverse transcription PCR (RT-qPCR) to analyze and compare gene expression changes between samples pre- and post-treatment. Our results substantiate the involvement of inflammatory and cell-growth related pathways and genes in the breast milk somatic cells following the intake of L. salivarius PS2. Individual analyses of selected genes: (1) supported the upregulation of STC1 and IL19 and the downregulation of PLAUR and IFNGR1 in the somatic cells of the patients as potential targets responsive to the probiotic, (2) detected a lack of a relationship between the gene expression responses in the two types of cells, and (3) evidenced a substantial interindividual variability in the gene expression changes in both types of cells. Our study provides an insight into the essentiality of incorporating the study of tissue-specific interindividual molecular responsivity into future clinical intervention trials to further understand the complexity of human gene expression responses to therapy and the potentiality of selecting appropriate responsive targets.

Critical Evaluation of Gene Expression Changes in Human Tissues in Response to Supplementation with Dietary Bioactive Compounds: Moving Towards Better-Quality Studies.

Pre-clinical cell and animal nutrigenomic studies have long suggested the modulation of the transcription of multiple gene targets in cells and tissues as a potential molecular mechanism of action underlying the beneficial effects attributed to plant-derived bioactive compounds. To try to demonstrate these molecular effects in humans, a considerable number of clinical trials have now explored the changes in the expression levels of selected genes in various human cell and tissue samples following intervention with different dietary sources of bioactive compounds. In this review, we have compiled a total of 75 human studies exploring gene expression changes using quantitative reverse transcription PCR (RT-qPCR). We have critically appraised the study design and methodology used as well as the gene expression results reported. We herein pinpoint some of the main drawbacks and gaps in the experimental strategies applied, as well as the high interindividual variability of the results and the limited evidence supporting some of the investigated genes as potential responsive targets. We reinforce the need to apply normalized procedures and follow well-established methodological guidelines in future studies in order to achieve improved and reliable results that would allow for more relevant and biologically meaningful results.

Meta-Analysis of the Effects of Foods and Derived Products Containing Ellagitannins and Anthocyanins on Cardiometabolic Biomarkers: Analysis of Factors Influencing Variability of the Individual Responses.

Understanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources of ellagitannins on a range of cardiometabolic risk biomarkers. The potential influence of various demographic and lifestyle factors on the variability in the response to these products were explored. Both anthocyanin- and ellagitannin-containing products reduced total-cholesterol with nuts and berries yielding more significant effects than pomegranate and grapes. Blood pressure was significantly reduced by the two main sources of anthocyanins, berries and red grapes/wine, whereas waist circumference, LDL-cholesterol, triglycerides, and glucose were most significantly lowered by the ellagitannin-products, particularly nuts. Additionally, we found an indication of a small increase in HDL-cholesterol most significant with nuts and, in flow-mediated dilation by nuts and berries. Most of these effects were detected in obese/overweight people but we found limited or non-evidence in normoweight individuals or of the influence of sex or smoking status. The effects of other factors, i.e., habitual diet, health status or country where the study was conducted, were inconsistent and require further investigation.