Polyphenols are bioactive molecules widely distributed in numerous foods such as fruits, vegetables, tea, coffee, cocoa and beverages. Their main classification include flavonoids (i.e. flavonols, flavones, flavanones, flavanols, anthocyanins, and isoflavones), non-flavonoids (i.e. lignans and stilbens) and phenolic acids (i.e. hydroxycinnamic and hydroxybenzoic acids)(1). Caffeic acid (CA) and chlorogenic acid (CGA; an ester of CA and quinic acid) are the major representatives of hydroxycinnamic acids. Accumulating evidence has demonstrated that CA and CGA may exert different biological activities, including antioxidant, anti-inflammatory, antidiabetic, and antihypertensive(2). Despite these promising and diverse anti-atherosclerotic actions, investigations addressing the effect of CA and CGA on atherogenesis are scarce.

The present study evaluated the capacity of CA and CGA to reduce lipid accumulation in macrophages derived from monocytic THP-1 cells. THP-1-derived macrophages were incubated with fatty acids (500 μM oleic/palmitic acid, 2:1 ratio) and different concentrations (from 0.03 to 3 μM) of CA and CGA, alone or in combination. Lipid accumulation was quantified spectrophotometrically (excitation: 544 nm, emission: 590 nm) with the fluorescent dye, Nile red. The fold increase compared to the control (without fatty acids) was calculated. In addition, the expression of several transcription factors including peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein (CEBP), as potential mechanisms involved in the regulation of lipid accumulation, was evaluated by real time PCR.

Analysis of variance (ANOVA) was used to assess the effect of the different concentrations of CA and CGA on lipid accumulation in THP-1 macrophages following stimulation with FA.

The preliminary results obtained have shown a significant increase in lipid accumulation following fatty acid exposure (p < 0.0001). Incubation with CA and CGA did not reduce lipid accumulation in THP-1 derived macrophages, while the combination of CA + CGA at 0.03, 0.3 and 3 μM (p < 0.01) decreased cellular fatty acid uptake at all concentrations tested by -28%, -32%, -23%, respectively. An apparent modulation of the transcriptional activity of PPARγ, but not CEBP, was observed following the combination of phenolic acids.

In conclusion, the incubation of CA + CGA at physiologically relevant concentrations, but not the single compounds, seem to reduce the uptake of fatty acids in THP-1-derived macrophages. Further experiments are ongoing in order to confirm the findings obtained and to better identify the mechanisms of action involved in the reduction of lipid accumulation as a key phenomenon of atherogenesis.

The endocannabinoid system is a lipid signalling system with several regulatory functions throughout the body including regulation of appetite, food intake, macronutrient metabolism, pain sensation, blood pressure, mood, cognition and immunity. It consists of endocannabinoids (ECs), their receptors and enzymes involved in their synthesis and degradation. The two best-characterized endocannabinoids are N-arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). They are ligands of cannabinoid receptors CB1 and CB2 which are located in the central nervous system (CNS) but also in in the enteric nervous system, in the liver and in the adipose tissue.

Several structural congeners of ECs including N-acylethanolamines (NAEs) such as oleoylethanolamine (OEA), linoleyethanolamine (LEA), and palmitoyletahanolamine (PEA), show similar mechanisms of action, tissue distribution as well as pathways of formation and breakdown. They are considered “endocannabinoid-like” molecules acting through receptors that are located both in CNS and in the gastro-intestinal tract mucosa such as the G-protein coupled receptor 119 (GPR119) and peroxisome proliferator-activated receptors (PPARs). NAEs display EC50 values for human GPR119 and PPAR-α between 65 ng/mL and 1000 ng/mL. Some evidence indicated that NAEs, their phosphorylated precursors N-acylphosphatidylethanolamines (NAPEs) and ECs are also present in food. Thus, we developed a food database of these molecules and we calculated the daily dietary intake in a healthy population.

This study aimed to evaluate whether the concentrations of NAPEs, NAEs and ECs in the human intestinal lumen may support their activity through the receptors lining in the gastro-intestinal tract and if they correlated with those in plasma.

The observational study (16/NI/0267, Ulster University) involved 35 ileostomists (18F/17M, aged 18–70 y, BMI 17–40 kg/m2) who collected overnight fasting samples of ileal fluid and plasma. The concentrations of NAEs, NAPEs and ECs in biological samples were determined by LC-HRMS.

Data showed that NAEs and NAPEs were present in ileal fluids and plasma from all subjects ranging between 46851.0–104742.8 ng/mL and 0.3–59.6 ng/mL in ileal samples and 1159.4–3985.7 ng/mL and 0.19–1.24 ng/mL in plasma, respectively. Contrarily, no ECs in ileal fluids were found except 2-AG in two ileal samples whereas they ranged between 1.6–22.3 ng/mL in plasma. Differences between genders and associations of plasma levels with individual energy intakes were found.

Altogether, the data demonstrated that NAEs in the intestinal lumen are sufficient to elicit metabolic responses through the gastro-intestinal receptors.

Apples are a rich source of polyphenols and fiber. Proanthocyanidins (PAs), the largest polyphenolic class in apples, can reach the colon almost intact where they interact with the gut microbiota producing simple phenolic acids. These metabolites have the potential to modulate gut microbiota composition and activity and impact on host physiology. A randomized, controlled, crossover, dietary intervention study was performed to determine the broad effects of whole apple intake on fecal gut microbiota composition and activity. Forty heathy mildly hypercholesterolemic volunteers (23 women, 17 men), with a mean BMI (± SD) 25.3 ± 3.7 kg/m2 and age 51 ± 11 years, consumed 2 apples/day (Renetta Canada, rich in PAs), or a sugar matched control apple beverage, for 8 weeks separated by a 4-week washout period in a random order. Fecal and 24-h urine samples were collected before and after each treatment. The broad effects of apple intake on fecal gut microbiota composition were explored by the high throughput sequencing (HTS) of 16S rRNA gene lllumina MiSeq sequencing (V3-V4 region). Sequencing data analysis was performed using the Quantitative Insight Into Microbial Ecology (QIIME) open-source pipeline version 1.9.1. Specific bacterial groups were also enumerated using the quantitative Fluorescence In Situ Hybridization (FISH). Furthermore, the potential formation of microbial polyphenol metabolites, after apple intake, was explored in urine using Liquid Chromatography (LC) High-Resolution Mass Spectrometry (HRMS) metabolomics. Preliminary analysis showed no changes in gut microbiota abundances measured by Illumina MiSeq, after correction for multiple testing. Apple intake significantly decreased Enterobacteriaceae population (P = 0.04) compared to the control beverage, as determined with FISH. Twenty-four polyphenol microbial metabolites were identified in higher concentrations in the apple group (P < 0.05) compared to the control, including valerolactones, valeric and phenolic acids. In conclusion, preliminary data suggest that the daily intake of 2 Renetta Canada apples significantly decreased Enterobacteriaceae population, a family known for its pathogenic members, in healthy mildly hypercholesterolemic subjects. Moreover, several polyphenol microbial metabolites were identified, suggesting that microbial activity is crucial and a prerequisite for the absorption of apple polyphenols, producing active metabolites with potential health benefits.

Platelet Activating Factor (PAF) is a pro-inflammatory mediator of atherogenesis. Food enriched with PAF inhibitors may have potential cardioprotective properties. In this attempt our group along with a well-known Greek dairy company incorporated bioactive ingredients (BAL) from olive-oil by-products, rich in PAF receptor specific inhibitors, into another typical food of the Mediterranean diet, namely yogurt. The aim of the present study was to evaluate the cardioprotective properties of the enriched yogurt in apparently healthy volunteers.

Ninety two apparently healthy volunteers (35–65 years) were randomly allocated into three groups by block-randomization based on age, sex and BMI. The volunteers in Group A did not consume any yogurt. The volunteers of Group B consumed a non-enriched yogurt daily. The Group C volunteers ate daily an enriched yogurt. The intervention lasted 8 weeks. Volunteers’ adherence to the study protocol was assessed by two 24 h recalls every two weeks conducted by trained personnel. Blood and urine samples were collected at baseline, at 4th week and at 8th week of the intervention and biochemical and inflammatory markers were determined. In addition, platelet aggregation in volunteers’ platelet rich plasma against PAF, ADP and TRAP were measured and the results expressed as the concentration of the agonist that cause 50% of the maximum aggregation (EC50, efficient concentration fifty values).

Among classical anthropometric and biochemical markers, only a decrease of blood pressure (systolic and diastolic) levels was observed (p0–8weeks < 0.05) in group B but with no clinical significance. Reduced levels of IL-10 was observed in group C compared to B both in the meantime (p4weeks = 0.01) and at the end of the intervention (p8weeks = 0.04). Furthermore, platelet sensitivity against PAF was only decreased (higher EC50 PAF,) in group C (p0–4weeks = 0.005 and p0–8weeks = 0.05). A trial effect was observed in the meantime among the three groups (p = 0.03).

The consumption of the enriched yogurt led to attenuation of subclinical inflammation and platelet sensitivity to thrombotic stimuli in apparently healthy volunteers, indicating a potential cardioprotective role of PAF inhibitors.

The work is funded by SYNERGASIA 2011 PROGRAMME. This Programme is co-funded by the European Regional Development Fund and National Resources, Project Code 11SYN-2-652.

A link has recently been underlined between one-carbon metabolism and body weight and body composition, suggesting that folate may account for body mass determination and lipid metabolism. The aim of this study was thus to analyze whether folate intake is associated with body weight, body mass index (BMI), body fat percentage, and liver status.

409 subjects aged 20–40 were enrolled in Poznań, Poland from 2016 to 2018. Food intake was assessed using three-day food records. Folate intake was calculated based on food composition tables using the Diet 5.0 program (National Food and Nutrition Institute, Poland). Weight to 0.1 kg and height to 0.01 m were measured using an electronic scale and a stadiometer, respectively. BMI was calculated as body weight in kilograms divided by height in meters squared. Fat mass and lean body mass were determined using whole-body air-displacement plethysmography (BodPod, Cosmed, Italy). Genotyping of rs1801133 (MTHFR) was performed with TaqMan probes. The following biomarkers of liver steatosis were calculated: NAFLD liver fat score (NAFLD-LFS), fatty liver index (FLI), and hepatic steatosis index (HSI). To analyze the associations between folate intake and the measured parameters, we used multiple regression with adjustments for age, sex, and energy intake.

The mean body weight was 78.57 ± 18.14 kg, BMI 25.96 ± 5.28 kg/m2, and fat percentage 29.20% ± 10.78%. The median folate intake was 299.3 μg/day. Dietary folate intake was negatively associated with body weight, BMI, and body fat percentage (p < 0.05 for all associations). Folate intake was also associated with fatty liver indices—namely HSI (p < 0.05) and FLI (p < 0.05). There was no association between folate intake and NAFLD-LFS. MTHFR rs1801133 polymorphism was not associated with any of the measured parameters.

Our findings suggest that folate intake may affect body weight and composition, as well as liver status. Higher folate intake could have a protective effect against obesity, but further studies are necessary to investigate the mechanism.

The authors declare that they have no conflict of interests.

This work was supported by the Polish National Science Centre

(grants 2014/15/B/NZ9/02134 and 2016/21/N/NZ9/01195).

Chronic stress is associated with impacting eating behavior, namely food choice and energy intake, with a shift towards more palatable and energy dense foods. Additionally, eating behavior is influenced by other psychological factors like mood and emotions. The categorization of people into eating types such as restrained, emotional, and external eaters has gained attraction. Reported changes in eating behavior due to psychological stress are only occasionally accompanied by measures of physiological hunger through ghrelin. The primary objective of this study was to investigate how chronic stress and acute cortisol reactivity affect active ghrelin secretion and how these outcomes account for different eating types. 16 healthy, young males (age: 23 ± 3 years, BMI: 22.5 ± 1.3kg/m2) with low (n = 8) and average-to-high (n = 8) chronic stress level were subjected to the Trier Social Stress Test (TSST) and a control version on two separate days. Active ghrelin, cortisol, glucose, and heart rate were measured throughout the test. Subjects rated their hunger by means of visual analog scale and current mood was assessed with the Positive and Negative Affect Scale (PANAS). In addition, participants filled out the Dutch Eating Behavior Questionnaire (DEBQ) to account for their subjective eating behavior. Overall ghrelin values where higher on the test day compared to the control day. Ghrelin values were also higher during the time leading up to the stress or control test (TSST) than during the conclusion of said tests. On both days, mean values for active ghrelin where higher in individuals with low chronic stress exposure compare to those with average-to-high chronic stress exposure. While values from test to control day decreased for lower stressed participants, they slightly increased for higher stressed participants. Cortisol responders displayed higher ghrelin values on test day than cortisol non-responders, but this association inverted for the control day. Results indicate that chronic stress influences acute stress response and further alters active ghrelin production, which in turn can influence eating behavior. Replication in a greater group of participants of differing weight and sex could yield a greater understanding of stress induced eating. Factors such as relaxation techniques and coping mechanisms could further improve our knowledge and evaluate treatment possibilities.

High diversity is considered a property of gut microbiota that is beneficial for human health. A higher dietary fiber intake has been shown to increase gut microbiota diversity. Similarly, there is preliminary evidence that an excess adiposity relates to low diversity. Our objective was to investigate the relationship between dietary fiber intake and gut microbiota diversity whilst considering the overweight and obesity status. Overweight (n = 52, prepregnancy BMI ≥ 25 kg/m2) and obese (n = 47, BMI ≥ 30 kg/m2) women were studied in early pregnancy (a mean of 13 weeks of gestation). The mean daily fiber intake (g) was calculated from 3-day food diaries by computerized software. To evaluate the gut microbiota α-diversity we determined the divergence-based measure, phylogenetic diversity (PD), and the qualitative and quantitative species-based measures, Chao 1 and Shannon index, from 16S RNA gene sequencing using QIIME pipeline. Dietary fiber intake (mean ± SD: 19.7 ± 6.2 g) correlated directly with PD (rho = 0.33, P = 0.002) and Chao 1 index (rho = 0.31, P = 0.004), but not with Shannon index (rho = 0.20, P = 0.06) in all women. Instead, no correlation between BMI and microbiota diversity indexes were seen, except for obese women in whom the BMI correlated inversely with PD (rho = -0.31, P = 0.04). Interestingly, distinct associations between fiber intake and microbiota diversity were detected in overweight and obese women. Fiber intake correlated directly with PD (rho = 0.34, P = 0.02 vs. rho = 0.32, P = 0.04), the measure depicting the phylogenetic branch length, in both overweight and obese women, the correlation with Chao 1 (rho = 0.35, P = 0.02), which depicts the presence or absence of each taxon i.e. richness, was seen only in obese women. Nevertheless, no correlation was seen between fiber intake and Shannon index (rho = -0.004, P = 0.98 vs. rho = -0.18, P = 0.25), the measure depicting the presence and absence as well as the abundance of each taxon i.e. richness and evenness, either in overweight or obese pregnant women. We found direct correlations between dietary fiber intake and gut microbiota α-diversity but obesity status intervened in this relation. In contrast to overweight women, in obese women, the higher dietary intake was reflected in a higher gut microbiota diversity measured at the level of taxon richness, suggesting that particularly obese pregnant women may benefit from a higher dietary fiber intake.

Bariatric surgery, including Gastric Bypass (GBP) Surgery, is the most efficient modality to manage severe obesity. Resting Energy Expenditure (REE) is an area of interest in the context of weight loss (WL) as it has been postulated to be an independent predictor of WL success following GBP. As such, the aim of this study is to investigate the impact of REE on WL following GBP. 31 GBP patients (77.4% females BMI 45.5 ± 7.0kg/m2 ; 47.3 ± 11.6y) and 32 weight-stable controls (46.9% females; BMI 27.0 ± 4.6kg/m2 ; 41.1 ± 13.5y) were assessed at one-month pre-surgery and at 3 and 12-months post-surgery. Fat mass (FM) and fat-free mass (FFM) were measured using dual energy X-ray absorptiometry (Lunar iDXA, GE Healthcare). REE was measured under standardised conditions using indirect calorimetry (ECAL, Metabolic Health Solutions). Statistical analyses were performed with SPSS v24.0, Armonk, NY. Multiple regression analysis showed that FM (P = 0.001), FFM (P < 0.0001) and gender (P = 0.012) significantly predicted the interindividual variability in REE. Total body weight (TBW) was removed from the model due to collinearity. Adjusted-REE values were then generated using the above predictor variables. Low-REE and high-REE groups were created using within-group adjusted-REE split. At both follow-ups (3- and 12-months post-surgery), patients had a greater reduction in TBW, FM, FFM, measured-REE and adjusted-REE values compared with controls (P < 0.0001). There was also no significant difference between measured and adjusted-REE values at all time-points (P > 0.05). Patients with high REEs at baseline lost more TBW than those in the low-REE group at 3-months post-surgery (-24.9 ± 6.5 kg vs. -16.6 ± 7.0 kg; P = 0.005) and 12-months post-surgery (-41.3 ± 12.5 kg vs. -25.8 ± 10.4.0 kg; P = 0.003). There was no significant difference in mean TBW changes for controls in the low-and high-REE groups at both follow-ups. Patients with high REEs at 3-months post-surgery did not lose more TBW than those in the low-REE group at 12-months post-surgery (-30.1 ± 12.8 kg vs. -38.6 ± 14.4 kg; P = 0.155). Similarly, there was no difference in mean TBW reduction between controls in the low- and high-REE groups (P = 0.115). Thus while patients with a high adjusted-REE value at baseline (> 9746.6kJ/day) lost more weight at 3- and 12-months post-GBP, it is plausible that from the third to the 12th month post-surgery, other key drivers of weight loss, particularly the reduction in energy intake are more important in predicting WL. Further research with a larger sample size is required to increase the chances of detecting a true effect.

The oxidative stress has been considered one of the main aspects related to psoriatic arthritis (PsA), diabetes, hypertension, obesity, dyslipidemia and metabolic syndrome. Based in the premise that there is a close relationship between the metabolic and inflammatory domain in PsA patients, our aim was to evaluate the role of a 12-week nutritional intervention, including hypocaloric diet and antioxidant supplementation, on inflammatory markers and disease activity in patients with PsA.

A total of 97 patients diagnosed with PsA (CASPAR, 2006) were included in this randomized, double-blinded placebo-controlled trial. Patients were distributed in three different groups: control (C) that received placebo (3 g of soybean oil); diet plus supplementation (DS) with hypocaloric diet plus omega 3 supplementation (3g); diet (D) with hypocaloric diet plus placebo supplementation (3 g of soybean oil). It was evaluated skin (PASI and BSA) and joint activity (DAS28-CRP, DAS28-ESR, BASDAI) and biochemical parameters, such as inflammatory markers (CRP, ESR, adiponectin, TBARs) and glucose and fat metabolism serum levels (HbA1c, fasting glucose and insulin, total cholesterol and fractions, triglycerides, AGER, oxidized- LDL, electronegative LDL (-) and anti-LDL (-) autoantibody) at baseline (T0) and after 12-week intervention (T3). Descriptive statistics are expressed as mean, standard deviation and frequency. Results were then compared using Kruskal-Wallis, ANOVA, Wilocoxon, Man-Whitney and T-Student test and multiple regressions. Level of significance was set as p < 0.05.

At baseline there was an increase of inflammatory markers (CRP, ESR, TBARs, AGER, LDL modifications), decrease of anti-inflammatory (adiponectin) and high prevalence of hypercholesterolemia (41.2%) and peripheral insulin resistance (60%). Our data showed a significant correlation between electronegative LDL and PASI and a correlation between AGER and DAS28-ESR, indicating that a decrease of inflammatory parameters could be related to skin and joint improvement. However, after 12-week nutritional intervention there has no improvement of proinflammatory markers in the group. There was only a significant increase of adiponectin serum levels in all 3 groups, suggesting a benefit effect on chronic inflammation. According our results, omega 3 supplementation was not more effective to improve inflammation, oxidative stress and disease activity.

Starch is one of the major sources of carbohydrates (CHO) contributing to about 50–70% of the daily energy intake in human diet. Processed foods contribute to an important part of daily energy intake, especially in occidental countries. During food processing, starch undergoes dramatic changes when heated in the presence of water or high pressure. The objective of this work was to evaluate the impact of controlling food processes on starch digestibility profile in cereal-based foods and the interest of preserving starch in its native, slowly digestible, form on in vivo metabolic fate.

Four different food processes were evaluated: extrusion, dry bread, soft cake and rotary-moulded biscuit. The resulting differences in gelatinization of each product translated to different SDS levels. Imaging techniques (X-ray diffraction, microtomography and electronic microscopy) were used to investigate the changes in SDS structure obtained through the different food processes. For in vivo evaluation, 12 healthy subjects were recruited and consumed a portion of 50 g of available CHOs of each product, in a crossover design. Glycemic and insulin responses were evaluated over 120 minutes in postprandial period.

We showed that rotary molding technology preserved starch in its intact form and provided the highest SDS content (28g/100g) when the three other technologies (dried bread, soft cake and extrusion) led to SDS content below 3g/100 g. In addition, the lowest SDS contents are explained by a higher level of starch structure disruption which translated in a shift from crystalline structure into amorphous one. These data were linked to in vivo results. The global analysis for GI indicated that a significant difference existed among the foods’ mean GI values (p < 0.0001). Rotary product showed the lowest GI values. The soft, the dried bread had medium GI and extruded product had the highest GI with 77. The global analysis for II indicated that a significant difference existed among the foods’ mean II values (p < 0.0001), with the same order as for GI values. In addition, a portion of rotary-molded biscuit decreased significantly the glycemic peak by 1 mM compared to the 3 other products.

Decrease of postprandial glycemia is a meaningful target in the prevention of metabolic diseases. This can be achieved through the modification of dietary factors such as starch digestibility.

The redox state of plasma albumin would reflect albumin synthesis rate, and could be useful to demonstrate the presence of potential protein undernutrition. Aiming to delineate the characteristics of plasma albumin redox state as a nutritional biomarker, adult male Wistar rats were maintained on AIN-93M (14% casein, control diet) or an AIN-93M-based low protein diet (5% casein) ad libitum for 4 weeks, and the two groups were compared by examining plasma albumin redox state, plasma/serum levels of conventional biomarkers for protein nutritional status, and plasma proteome. While no significant difference was seen in body weight at the end of the experimental period, plantaris muscle mass trended lower in the low protein diet group, implicating the manifestation of moderate protein undernutrition. The redox of plasma albumin was shifted to more oxidized state in the low protein diet group, and the shift persisted during the entire experimental period. In contrast, the levels of conventional biomarkers, plasma albumin and prealbumin, were initially decreased in the low protein diet group, and the differences were then dissolved later in the experimental period. Similarly, the levels of other biomarkers, plasma transferrin and serum retinol-binding protein-4, did not differ significantly at the end of the experimental period. Plasma proteomic analysis revealed that the abundances of proteins that constitute high-density lipoprotein (HDL), apolipoprotein A-II and paraoxonase-1, were decreased in the low protein diet group, which were then validated by confirming decreases in plasma HDL level, plasma HDL-cholesterol level, and serum paraoxonase-1 activity in the low protein diet group. According to epidemiological reports, dietary protein intake is positively associated with plasma HDL-cholesterol level, and the risk factors of cardiovascular diseases, including lower HDL-cholesterol level, are closely related to frailty. Thus, it can be conceived that moderate dietary protein insufficiency would increase cardiovascular risks, such as reduction in HDL level and function (paraoxonase-1 activity), which could prime the onset of amyotropic diseases later in life, such as sarcopenia and frailty. Collectively, moderate dietary protein insufficiency would lead to decreased skeletal muscle mass, and also attenuate circulating HDL level and function, which could even aggravate the attenuation of skeletal muscle accretion; the redox state of plasma albumin would be instrumental over conventional biomarkers as an indicator of potentially protein undernourished status.