Effect of Barley and Oat Consumption on Immune System, Inflammation and Gut Microbiota: A Systematic Review of Randomized Controlled Trials.

PURPOSE OF REVIEW: The aim of this systematic review was to investigate the effects of whole grain Avena sativa and Hordeum vulgare L., or their isolated fractions, on immune and inflammatory functions, as well as their influence on gut microbiota. A structured literature search was undertaken in line with PRISMA guidelines. Randomized controlled trials (RCTs) that investigated the effects of oats or barley consumption in adults and reported ≥ 1 of the following: C-reactive protein (CRP), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), IL-2, IL-8, IL-18, lipopolysacharide binding protein (LBP) or gut microbiota-related outcomes, were included. RECENT FINDINGS: A total of 16 RCTs were included, among which 6 studies recruited metabolically at-risk population, including individuals with overweight and obesity, metabolic syndrome or hypercholesterolemia. Additionally, 3 trials involved young healthy population, 5 trials targeted older individuals (aged over 50 years), and 2 studies encompassed populations with other disease states. A total of 1091 individuals were included in the evaluation of short-term (up to 14 days) and long-term (beyond 14 days, up to 90 days) supplementation with oats or barley-based products. 9 studies measured inflammatory biomarkers and 5 of them reported significant reductions, specifically in long-term studies. Notably, no evidence of anti-inflammatory benefits was found in healthy individuals, whereas studies involving metabolically at-risk populations showed promising reductions in inflammation. 13 studies measured the impact on gut microbiota, and collectively suggest that oats and barley food products can influence the composition of gut microbiota, associated in some cases with metabolic improvements. Oats and barley consumption may confer anti-inflammatory effects in metabolically at-risk populations and influence gut microbiota outcomes. However, no anti-inflammatory benefits were observed in healthy individuals. Results from this systematic review suggests caution in interpreting findings due to limited trials and variations in interventions and health conditions.

Bioactive Compounds and Antioxidant Capacity in Pearling Fractions of Hulled, Partially Hull-Less and Hull-Less Food Barley Genotypes.

Three food barley genotypes differing in the presence or absence of husks were sequentially pearled and their fractions analyzed for ash, proteins, bioactive compounds and antioxidant capacity in order to identify potential functional food ingredients. Husks were high in ash, arabinoxylans, procyanidin B3, prodelphinidin B4 and p-coumaric, ferulic and diferulic bound acids, resulting in a high antioxidant capacity. The outermost layers provided a similar content of those bioactive compounds and antioxidant capacity that were high in husks, and also an elevated content of tocols, representing the most valuable source of bioactive compounds. Intermediate layers provided high protein content, ß-glucans, tocopherols and such phenolic compounds as catechins and bound hydroxybenzoic acid. The endosperm had very high ß-glucan content and relative high levels of catechins and hydroxybenzoic acid. Based on the spatial distribution of the bioactive compounds, the outermost 30% pearling fractions seem the best option to exploit the antioxidant capacity of barley to the full, whereas pearled grains supply ß-glucans enriched flours. Current regulations require elimination of inedible husks from human foods. However, due to their high content in bioactive compounds and antioxidant capacity, they should be considered as a valuable material, at least for animal feeds.

Virgin Olive Oil Phenolic Compounds Modulate the HDL Lipidome in Hypercholesterolaemic Subjects: A Lipidomic Analysis of the VOHF Study.

SCOPE: The lipidomic analysis of high-density lipoprotein (HDL) could be useful to identify new biomarkers of HDL function. METHODS AND RESULTS: A randomized, controlled, double-blind, crossover trial (33 hypercholesterolaemic subjects) is performed with a control virgin olive oil (VOO), VOO enriched with its own phenolic compounds (FVOO), or VOO enriched with additional phenolic compounds from thyme (FVOOT) for 3 weeks. HDL lipidomic analyses are performed using the Lipidyzer platform. VOO and FVOO intake increase monounsaturated-fatty acids (FAs) and decrease saturated and polyunsaturated FAs in triacylglyceride (TAG) species, among others species. In contrast, FVOOT intake does not induce these FAs changes. The decrease in TAG52:3(FA16:0) after VOO intake and the decrease in TAG52:5(FA18:2) after FVOO intake are inversely associated with changes in HDL resistance to oxidation. After FVOO intake, the decrease in TAG54:6(FA18:2) in HDL is inversely associated with changes in HDL cholesterol efflux capacity. CONCLUSION: VOO and FVOO consumption has an impact on the HDL lipidome, in particular TAG species. Although TAGs are minor components of HDL mass, the observed changes in TAG modulated HDL functionality towards a cardioprotective mode. The assessment of the HDL lipidome is a valuable approach to identify and characterize new biomarkers of HDL function.

Consumption evaluation of one apple flesh a day in the initial phases prior to adenoma/adenocarcinoma in an azoxymethane rat colon carcinogenesis model.

Colorectal cancer (CRC) is the fourth cancer with the most new cases reported in 2018 worldwide. Consumption of fruit and vegetables is a protective factor against the risk of CRC. Beyond this, flavonoids could orchestrate these healthy effects. Apart from containing the typical apple flavonoids, red-fleshed apples also contain anthocyanins, mainly cyanidin-3-O-galactoside (Cy3Gal). Through an azoxymethane rat carcinogenesis model, a study was carried out in order to assess the possible protective effects of apple polyphenols, with special attention to anthocyanins. In addition, apart from negative and positive controls, a group with chemotherapy with 5-fluorouracil (5FU) was included to compare their performance against the output collected from the animal treatments with white-fleshed apple (WF), red-fleshed apple (RF) and Cy3Gal (AE). Although the 5FU group presented the best performance towards aberrant crypt foci (ACF) inhibition (70.1%), rats fed with white-fleshed apples ('Golden Smoothee') were able to achieve 41.3% ACF inhibition, while none of the challenged treatments (WF, RF and AE) suffered mucin depletion in their colonocytes. Expression changes of 17 genes related to CRC were assessed. In detail, the ACF inhibition phenotype detected in 5FU and WF groups could be explained through the expression changes detected in the apoptosis-related genes of Aurka, p53 and Cox2. Moreover, in the apple consumption groups (WF and RF), a reduced protein expression of matrix metalloproteinases with gelatinase activity (MMP-2 and 9) was detected. Overall, our study suggests an effect of apple polyphenols and apple anthocyanin Cy3Gal against colon carcinogenesis, retarding/diminishing the appearance of the precancerous markers studied.

Berry-Enriched Diet in Salt-Sensitive Hypertensive Rats: Metabolic Fate of (Poly)Phenols and the Role of Gut Microbiota.

Diets rich in (poly)phenols are associated with a reduced reduction in the incidence of cardiovascular disorders. While the absorption and metabolism of (poly)phenols has been described, it is not clear how their metabolic fate is affected under pathological conditions. This study evaluated the metabolic fate of berry (poly)phenols in an in vivo model of hypertension as well as the associated microbiota response. Dahl salt-sensitive rats were fed either a low-salt diet (0.26% NaCl) or a high-salt diet (8% NaCl), with or without a berry mixture (blueberries, blackberries, raspberries, Portuguese crowberry and strawberry tree fruit) for 9 weeks. The salt-enriched diet promoted an increase in the urinary excretion of berry (poly)phenol metabolites, while the abundance of these metabolites decreased in faeces, as revealed by UPLC-MS/MS. Moreover, salt and berries modulated gut microbiota composition as demonstrated by 16S rRNA analysis. Some changes in the microbiota composition were associated with the high-salt diet and revealed an expansion of the families Proteobacteria and Erysipelotrichaceae. However, this effect was mitigated by the dietary supplementation with berries. Alterations in the metabolic fate of (poly)phenols occur in parallel with the modulation of gut microbiota in hypertensive rats. Thus, beneficial effects of (poly)phenols could be related with these interlinked modifications, between metabolites and microbiota environments.

Endothelial Cells Deconjugate Resveratrol Metabolites to Free Resveratrol: A Possible Role in Tissue Factor Modulation.

SCOPE: The antithrombotic effects of resveratrol (RV) and its derivatives remain unknown. The objective is to evaluate the modulatory effects of RV, its glucoside form, piceid, and its biological metabolites (RV-3-O-ß-d-glucuronide, RV-4'-O-d-glucuronide, and RV-3-O-sulfate) on tissue factor (TF). Moreover, the endothelial metabolism of RV is assessed. METHODS AND RESULTS: Human aortic endothelial cells (HAECs) are incubated with trans-piceid, trans-RV, or their biological metabolites and stimulated with tumor necrosis factor-α (TNF-α). TF activity, protein levels, and mRNA expression are determined in cell lysates. Moreover, RV conjugation (phase-II-metabolism) to its sulfated or glucuronidated metabolites and their deconjugation to their parent compound (free RV) are also assessed in cell lysates and culture media. RV decreased TF activity, protein levels, and mRNA expression, whereas piceid and RV metabolites (RVmet) had no effects. RV-3-O-sulfate was the main metabolite generated in the endothelium, while RVmet are deconjugated to free RV. Isomerization of trans-RV and its trans-metabolites to their cis-forms is observed. CONCLUSIONS: RV exerts antithrombotic effects by modulating TF. RVmet and piceid does not exert this effect. However, the capacity of endothelial cells to deconjugate RVmet to free RV indicates that RVmet function as an endothelial reservoir for RV regeneration, thus, contributing to the antithrombotic effects of RV.

Validation of Dried Blood Spot Cards to Determine Apple Phenolic Metabolites in Human Blood and Plasma After an Acute Intake of Red-Fleshed Apple Snack.

SCOPE: The application of dried blood spot (DBS) cards for the study in human blood of dietary polyphenol bioavailability has been poorly studied. METHODS AND RESULTS: An analytical method based on blood sampling with DBS cards combined with LC-MS/MS has been developed and validated. To test the method validation, the phenolic metabolites are determined in human blood and plasma obtained after an acute intake of a red-fleshed apple snack in ten volunteers. Capillary blood by finger prick is compared to venous blood by venipuncture and whole blood is also compared to their corresponding venous plasma samples. Moreover, the venous plasma results using DBS cards are compared to those obtained by microElution solid phase extraction (µSPE). The main phenolic metabolites detected in blood and plasma samples are phloretin glucuronide, dihydroxyphenylpropionic acid sulphate, (methyl) catechol sulphate, catechol glucuronide, and hydroxyphenyl-γ-valerolactone glucuronide. No significant differences are observed between capillary blood, venous blood, and plasma samples using DBS, and neither between plasma samples analyzed by DBS or µSPE. CONCLUSIONS: Finger-prick blood sampling based on DBS appears to be a suitable alternative to the classic invasive venipuncture for the determination of circulating phenolic metabolites in nutritional postprandial studies.

Cardiovascular Benefits of Phenol-Enriched Virgin Olive Oils: New Insights from the Virgin Olive Oil and HDL Functionality (VOHF) Study.

SCOPE: The main findings of the "Virgin Olive Oil and HDL Functionality" (VOHF) study and other related studies on the effect of phenol-enriched virgin olive oil (VOO) supplementation on cardiovascular disease are integrated in the present work. METHODS AND RESULTS: VOHF assessed whether VOOs, enriched with their own phenolic compounds (FVOO) or with those from thyme (FVOOT), improve quantity and functionality of HDL. In this randomized, double-blind, crossover, and controlled trial, 33 hypercholesterolemic subjects received a control VOO (80 mg kg-1 ), FVOO (500 mg kg-1 ), and FVOOT (500 mg kg-1 ; 1:1) for 3 weeks. Both functional VOOs promoted cardioprotective changes, modulating HDL proteome, increasing fat-soluble antioxidants, improving HDL subclasses distribution, reducing the lipoprotein insulin resistance index, increasing endogenous antioxidant enzymes, protecting DNA from oxidation, ameliorating endothelial function, and increasing fecal microbial metabolic activity. Additional cardioprotective benefits were observed according to phenol source and content in the phenol-enriched VOOs. These insights support the beneficial effects of OO and PC from different sources. CONCLUSION: Novel therapeutic strategies should increase HDL-cholesterol levels and enhance HDL functionality. The tailoring of phenol-enriched VOOs is an interesting and useful strategy for enhancing the functional quality of HDL, and thus, it can be used as a complementary tool for the management of hypercholesterolemic individuals.

Hydroxytyrosol: Emerging Trends in Potential Therapeutic Applications.

Hydroxytyrosol (HT) and its derivatives represent the minor components of Virgin Olive Oil (VOO) that are of great interest for their pharmacological properties and among the most widely researched natural antioxidant compounds. In this review, the occurrence and metabolic fate of HT and its precursors are presented prior to discussing its beneficial effects on health. Bioavailability studies show that the metabolites detected in plasma depend on the model used (animal or human), the HT source (simple molecule or complex precursors) and the dose administered. However, in all cases HT sulphate appears to be the most ubiquitous metabolite in biofluids and it seems probable that it is responsible to a great extent for HT biological effects. Epidemiological evidence of HT and its derivatives against such lifestyle-associated pathologies as cancer, cardiovascular and neurodegenerative diseases is reviewed together with the newest perspectives on the mechanisms of action based on in-vitro and animal studies. According to the reviewed data, HT and its precursors could have the potential clinical use in cardiovascular diseases; more epidemiological data is needed to demonstrate their neurodegenerative diseases and cancer prevention.

Phytochemical Profiles of New Red-Fleshed Apple Varieties Compared with Traditional and New White-Fleshed Varieties.

This study is an exhaustive chemical characterization of the phenolic compounds, triterpenes, and organic and ascorbic acids in red-fleshed apple varieties obtained by different breeding programs and using five traditional and new white-fleshed apple cultivars as reference. To carry out these analyses, solid-liquid extraction (SLE) and ultraperformance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) were used. The results showed that the red-fleshed apples contained, in either the flesh or peel, higher amounts of phenolic acids (chlorogenic acid), anthocyanins (cyanidin-3-O-galactoside), dihydrochalcones (phloretin xylosyl glucoside), and organic acids (malic acid) but a lower amount of flavan-3-ols than the white-fleshed apples. These quantitative differences could be related to an up-regulation of anthocyanins, dihydrochalcones, and malic acid and a down-regulation of flavan-3-ols (anthocyanin precursors) in both the flesh and peel of the red-fleshed apple varieties. The reported results should be considered preliminary because the complete phytochemical characterization of the red-fleshed apple cultivars will be extended to consecutive harvest seasons.

Hydroxytyrosol and the Colonic Metabolites Derived from Virgin Olive Oil Intake Induce Cell Cycle Arrest and Apoptosis in Colon Cancer Cells.

After the sustained consumption of virgin olive oil (VOO), the unabsorbed native phenols (mainly hydroxytyrosol (HT)) are transformed into its catabolites in the intestine by microbials. The role of these catabolites in preventing colon cancer has not been sufficiently investigated. This work aims to study the antiproliferative and apoptotic activities in colon (Caco-2; HT-29) cancer cell lines of the main catabolites detected in human feces (phenylacetic, phenylpropionic, hydroxyphenylpropionic, and dihydroxyphenylpropionic acids and catechol), after the sustained VOO intake. Additionally, an assessment of the ability of these colonic cells to metabolize the studied compounds was performed. The results showed that HT and phenylacetic and hydroxyphenylpropionic acids produce cell cycle arrest and promote apoptosis. HT-29 cells were more sensitive to phenol treatments than Caco-2. In synthesis, the results of the present study represent a good starting point for understanding the potential apoptotic and antiproliferative effects of VOO phenolic compounds and their colonic metabolites.

Exploring the Colonic Metabolism of Grape and Strawberry Anthocyanins and Their in Vitro Apoptotic Effects in HT-29 Colon Cancer Cells.

Beneficial properties attributed to the intake of fruit and red wine have been associated with the presence of significant amounts of anthocyanins. However, their low absorption and consequent accumulation in the gut have generated the suspicion that colonic metabolites of anthocyanins are probably involved in these protective effects. Grape pomace and strawberry extracts, rich in malvidin- and pelargonidin-glucoside, respectively, were fermented in vitro using human feces as microbial inoculum. After 8 h of anaerobic incubation, the anthocyanins were almost completely degraded, whereas their microbial metabolite concentrations were highest at 24 h. Syringic acid and tyrosol were the main metabolites of grape and strawberry extracts, respectively. On the basis of the metabolites detected, metabolic pathways of malvidin- and pelargonidin-glucosides were proposed. Anthocyanin-rich grape and strawberry extracts and their generated metabolites such as hydroxyphenylacetic acid showed apoptotic effects in HT-29 colon cancer cells and may suggest their possible contribution as anticarcinogenic agents.

Application of dried blood spot cards to determine olive oil phenols (hydroxytyrosol metabolites) in human blood.

In this study, a fast and simple blood sampling and sample pre-treatment method based on the use of the dried blood spot (DBS) cards and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) for the quantification of olive oil phenolic metabolites in human blood was developed and validated. After validation, the method was applied to determine hydroxytyrosol metabolites in human blood samples after the acute intake of an olive oil phenolic extract. Using the FTA DMPK-A DBS card under optimum conditions, with 20µL as the blood solution volume, 100µL of methanol/Milli-Q water (50/50, v/v) as the extraction solvent and 7 disks punched out from the card, the main hydroxytyrosol metabolites (hydroxytyrosol-3-O-sulphate and hydroxytyrosol acetate sulphate) were identified and quantified. The developed methodology allowed detecting and quantifying the generated metabolites at low µM levels. The proposed method is a significant improvement over existing methods to determine phenolic metabolites circulating in blood and plasma samples, thus making blood sampling possible with the volunteer pricking their own finger, and the subsequent storage of the blood in the DBS cards prior to chromatographic analysis.

Polyphenol rich olive oils improve lipoprotein particle atherogenic ratios and subclasses profile: A randomized, crossover, controlled trial.

SCOPE: Lipoprotein particle measures performed by nuclear magnetic resonance (NMR), and associated ratios, may be better markers for atherosclerosis risk than conventional lipid measures. The effect of two functional olive oils, one enriched with its polyphenols (FVOO, 500 ppm), and the other (FVOOT) with them (250 ppm) and those of thyme (250 ppm), versus a standard virgin olive oil (VOO), on lipoprotein particle atherogenic ratios and subclasses profiles was assessed. METHODS AND RESULTS: In a randomized, double-blind, crossover, controlled trial, 33 hypercholesterolemic individuals received 25 mL/day of VOO, FVOO, and FVOOT. Intervention periods were of 3 weeks separated by 2-week washout periods. Lipoprotein particle counts and subclasses were measured by NMR. Polyphenols from olive oil and thyme modified the lipoprotein subclasses profile and decreased the total LDL particle/total HDL particle (HDL-P), small HDL/large HDL, and HDL-cholesterol/HDL-P ratios, and decreased the lipoprotein insulin resistance index (LP-IR) (p < 0.05). CONCLUSION: Olive oil polyphenols, and those from thyme provided benefits on lipoprotein particle atherogenic ratios and subclasses profile distribution. Polyphenol-enriched olive oil is a way of increasing the olive oil healthy properties while consuming the same amount of fat, as well as a useful and complementary tool for the management of cardiovascular risk individuals.

Stability and metabolism of Arbutus unedo bioactive compounds (phenolics and antioxidants) under in vitro digestion and colonic fermentation.

The natural antioxidants of Arbutus unedo highlight the importance of this fruit as natural source of bioactive compounds. In the present study, to evaluate the stability of phenolic compounds, ascorbic acid and fat-soluble antioxidants (α-tocopherol, ß-carotene and lutein), in vitro gastrointestinal digestion was applied to A. unedo fruit. After that, the non-absorbable fraction was anaerobically incubated with human faeces and the metabolic pathway for gallotannins, ellagitannins, flavan-3-ols and anthocyanins from A. unedo fruit was proposed. The results showed that the presence of pectin from the fruit hampered the solubilization of the phenolic compounds (with exception of gallic and ellagic acids) and fat-soluble vitamins during gastric digestion. Degradation of pectin-gel during the duodenal digestion favored the release of the phenolic compounds and fat-soluble antioxidants to the media. The catabolic activity of human microbiota led to the generation of a wide range of simple phenols, such as p-hydroxybenzoic acid and catechol, derived from the catabolism of gallotannins, ellagitannins, flavan-3-ols and anthocyanins.

Metabolic and Microbial Modulation of the Large Intestine Ecosystem by Non-Absorbed Diet Phenolic Compounds: A Review.

Phenolic compounds represent a diverse group of phytochemicals whose intake is associated with a wide spectrum of health benefits. As consequence of their low bioavailability, most of them reach the large intestine where, mediated by the action of local microbiota, a series of related microbial metabolites are accumulated. In the present review, gut microbial transformations of non-absorbed phenolic compounds are summarized. Several studies have reached a general consensus that unbalanced diets are associated with undesirable changes in gut metabolism that could be detrimental to intestinal health. In terms of explaining the possible effects of non-absorbed phenolic compounds, we have also gathered information regarded their influence on the local metabolism. For this purpose, a number of issues are discussed. Firstly, we consider the possible implications of phenolic compounds in the metabolism of colonic products, such as short chain fatty acids (SCFA), sterols (cholesterol and bile acids), and microbial products of non-absorbed proteins. Due to their being recognized as affective antioxidant and anti-inflammatory agents, the ability of phenolic compounds to counteract or suppress pro-oxidant and/or pro-inflammatory responses, triggered by bowel diseases, is also presented. The modulation of gut microbiota through dietetic maneuvers including phenolic compounds is also commented on. Although the available data seems to assume positive effects in terms of gut health protection, it is still insufficient for solid conclusions to be extracted, basically due to the lack of human trials to confirm the results obtained by the in vitro and animal studies. We consider that more emphasis should be focused on the study of phenolic compounds, particularly in their microbial metabolites, and their power to influence different aspects of gut health.

Faecal microbial metabolism of olive oil phenolic compounds: in vitro and in vivo approaches.

SCOPE: In the present study, the individual colonic metabolism of the main components of the virgin olive oil phenolic fraction was evaluated by an in vitro model using human faecal microbiota. To assess differences in metabolism related to the molecular structure, four phenolic standards were selected, tyrosol, hydroxytyrosol, hydroxytyrosol acetate and oleuropein. After studying the in vitro colonic metabolism pathways of the individual phenols, the presence of their colonic metabolites was investigated in human faecal samples obtained before and after the sustained intake (3 weeks) of a daily dose of 25 mL of a phenol-enriched olive oil. METHODS AND RESULTS: The in vitro colon fermentation of the four individual phenolic compounds revealed (i) an increase in phenolic acids, (ii) the stability of hydroxytyrosol and tyrosol and (iii) the high degradation of hydroxytyrosol acetate and oleuropein. Additionally, a moderate intake of a phenol-rich olive oil raised the concentration in human faeces of free hydroxytyrosol and phenylacetic and phenylpropionic acids. CONCLUSION: The products of colonic catabolism of olive oil phenolic compounds could be good candidates for novel preventive strategies and open a promising line of research into the preventive action of olive oil phenols in colon and other bowel diseases.

Optimisation and validation of analytical methods for the simultaneous extraction of antioxidants: application to the analysis of tomato sauces.

In the present study, simultaneous extraction of natural antioxidants (phenols and carotenoids) in complex matrices, such as tomato sauces, is presented. The tomato sauce antioxidant compounds studied were the phenolics hydroxytyrosol, from virgin olive oil, quercetin and its derivatives, from onions, and quercetin-rutinoside as well as the carotenoid, lycopene (cis and trans), from tomatoes. These antioxidant compounds were extracted simultaneously with n-hexane/acetone/ethanol (50/25/25, v/v/v). The phenolics were analysed by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS), and lycopene (cis- and trans-forms) was analysed using high-performance liquid chromatography coupled to a diode array detector (HPLC-DAD). After studying the parameters of these methods, they were applied to the analysis of virgin olive oil, fresh onion, tomato concentrate and tomato powder, and commercial five tomato sauces. Subsequently, the results obtained in our laboratory were compared with those from the Gallina Blanca Star Group laboratory.

Effect of the co-occurring components from olive oil and thyme extracts on the antioxidant status and its bioavailability in an acute ingestion in rats.

The aim of this work was to examine whether bioactives in thyme could enhance the antioxidant capacity of phenolics in virgin olive oil and their bioavailability in Wistar rats. After acute oral administration of extracts from olive cake (OE), thyme (TE) or their combination (OTE), blood samples were collected from 0 to 360 min. Plasma antioxidant status was analyzed by DPPH and FRAP in plasma and by SOD, CAT and GPx activities in erythrocytes. Plasma pharmacokinetics of the main metabolites of bioactives in olive oil and thyme were characterized. Plasma non-enzymatic antioxidant capacity was significantly modulated by OE, TE, and OTE in a time-, assay, and extract-dependent manner. OE, TE, and OTE all significantly decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity and catalase (CAT) activity was increased. Pharmacokinetic results showed that plasma concentration (Cmax) of the main olive phenolic metabolites in rats fed with OTE were similar to those of OE. These results indicate that an enhanced bioavailability of olive phenolic compounds could occur in the presence of thyme, although any synergistic effect was observed in the antioxidant status when both phenolic extracts were administered. Antioxidant protection by phenolics from olive and thyme against oxidative stress occurs primarily through a direct antioxidant effect and may be related to the phenolic plasmatic metabolites.