No evidence of differential impact of sunflower and rapeseed oil on biomarkers of coronary artery disease or chronic kidney disease in healthy adults with overweight and obesity: result from a randomised control trial.

PURPOSE: The perceived benefits and risks associated with seed oil intake remain controversial, with a limited number of studies investigating the impact of intake on a range of compounds used as cardiometabolic markers. This study aimed to explore the proteomic and cardiometabolic effects of commonly consumed seed oils in the UK, with different fatty acid profiles. METHODS: In a parallel randomised control design, healthy adults (n = 84), aged 25-72 with overweight or obesity were randomised to one of three groups: control (habitual diet, CON); 20 mL rapeseed oil per day (RO), or 20 mL sunflower oil per day (SO). Blood, spot urine and anthropometric measures were obtained at 0, 6 and 12 weeks. Proteomic biomarkers analysis was conducted for coronary arterial disease (CAD) and chronic kidney disease (CKD) using capillary electrophoresis coupled to mass spectrometry (CE-MS). Blood lipids, fasting blood glucose, glycative/oxidative stress and inflammatory markers were also analysed. RESULTS: No differences in change between time points were observed between groups for CAD or CKD peptide fingerprint scores. No change was detected within groups for CAD or CKD scores. No detectable differences were observed between groups at week 6 or 12 for the secondary outcomes, except median 8-isoprostane, ~ 50% higher in the SO group after 12-weeks compared to RO and CON groups (p = 0.03). CONCLUSION: The replacement of habitual fat with either RO or SO for 12 weeks does not lead to an improvement or worsening in cardiovascular health markers in people with overweight or obesity. TRIAL REGISTRATION: Trial registration clinicaltrials.gov NCT04867629, retrospectively registered 30/04/2021.

The role of faecal calprotectin in diagnosis and staging of colorectal neoplasia: a systematic review and meta-analysis.

INTRODUCTION: The presence of inflammation is a key hallmark of cancer and, plays an important role in disease progression and survival in colorectal cancer (CRC). Calprotectin detected in the faeces is a sensitive measure of colonic inflammation. The role of FC as a diagnostic test that may categorise patients by risk of neoplasia is poorly defined. This systematic review and meta-analysis aims to characterise the relationship between elevations of FC and colorectal neoplasia. METHODS: A systematic review was performed using the keywords (MESH terms) and a statistical and meta-analysis was performed. RESULTS: A total of 35 studies are included in this review. CRC patients are more likely than controls to have an elevated FC OR 5.19, 95% CI 3.12-8.62, p < 0.001 with a heterogeneity (I2 = 27%). No tumour characteristics significantly correlated with FC, only stage of CRC shows signs that it may potentially correlate with FC. CONCLUSION: FC levels are significantly higher in CRC, with high sensitivity. Its low specificity prevents it from being used to diagnose or screen for CRC.

The role of faecal calprotectin in the identification of colorectal neoplasia in patients attending for screening colonoscopy.

AIM: Although the relationship between colorectal neoplasia and inflammation is well described, the role of faecal calprotectin (FC) in clinical practice to diagnose or screen patients for colorectal neoplasia is less defined. This prospective study characterizes the relationship between FC and colorectal neoplasia in patients within the faecal occult blood testing (FOBT) positive patients in the Scottish Bowel Screening Programme. METHODS: All FOBT positive patients attending for colonoscopy between February 2016 and July 2017 were invited to participate. Patients provided a stool sample for FC before commencing bowel preparation. All demographics and endoscopic findings were collected prospectively. RESULTS: In all, 352 patients were included. 210 patients had FC > 50 µg. Colorectal cancer (CRC) patients had a higher median FC (138.5 µg/g, P < 0.05), in comparison to those without CRC, and 13/14 had an FC > 50 µg/g (93%). FC had a high sensitivity (92.8%) and negative predictive value (99.3%) for CRC, but with a low specificity (41.7%) and positive predictive value (6.2%). FC sensitivity increased sequentially as neoplasms progressed from non-advanced to malignant neoplasia (48.6% non-advanced adenoma vs. 92.9% CRC). However, no significant relationship was observed between FC and non-cancer neoplasia. CONCLUSION: In an FOBT positive screening population, FC was strongly associated with CRC (sensitivity 92.8%, specificity 41.7% for CRC, at 50 µg/g). However, although sensitive for the detection of CRC, FC failed to show sufficient sensitivity or specificity for the detection of non-cancer neoplasia. Based on these results we cannot recommend routine use of FC in a bowel screening population to detect cancer per se, but it is apparent that, with further optimization, faecal assessments including quantification of haemoglobin and inflammation could form part of a risk assessment tool aimed at refining the selection of patients for colonoscopy in both symptomatic and screening populations.

Socioeconomic position links circulatory microbiota differences with biological age.

Imbalanced nutrition is associated with accelerated ageing, possibly mediated by microbiota. An analysis of the circulatory microbiota obtained from the leukocytes of participants in the MRC Twenty-07 general population cohort was performed. We now report that in this cohort, the most biologically aged exhibit a significantly higher abundance of circulatory pathogenic bacteria, including Neisseria, Rothia and Porphyromonas, while those less biologically aged possess more circulatory salutogenic (defined as being supportive of human health and wellbeing) bacteria, including Lactobacillus, Lachnospiraceae UCG-004 and Kocuria. The presence of these salutogenic bactreria is consistent with a capacity to metabolise and produce Nrf2 agonists. We also demonstrate that associated one carbon metabolism, notably betaine levels, did not vary with chronological age, but displayed a difference with socioeconomic position (SEP). Those at lower SEP possessed significantly lower betaine levels indicative of a poorer diet and poorer health span and consistent with reduced global DNA methylation levels in this group. Our data suggest a clear route to improving age related health and resilience based on dietary modulation of the microbiota.

Dietary Fibres Differentially Impact on the Production of Phenolic Acids from Rutin in an In Vitro Fermentation Model of the Human Gut Microbiota.

Polyphenols are often ingested alongside dietary fibres. They are both catabolised by, and may influence, the intestinal microbiota; yet, interactions between them and the impact on their resultant microbial products are poorly understood. Dietary fibres (inulin, pectin, psyllium, pyrodextrin, wheat bran, cellulose-three doses) were fermented in vitro with human faeces (n = 10) with and without rutin (20 µg/mL), a common dietary flavonol glycoside. Twenty-eight phenolic metabolites and short chain fatty acids (SCFA) were measured over 24 h. Several phenolic metabolites were produced during fibre fermentation, without rutin. With rutin, 3,4-dihydroxyphenylacetic acid (3,4diOHPAA), 3-hydroxyphenylacetic acid (3OHPAA), 3-(3 hydroxyphenyl)propionic acid (3OHPPA) and 3-(3,4-dihydroxyphenyl)propionic acid (3,4diOHPPA; DOPAC) were produced, with 3,4diOHPAA the most abundant, confirmed by fermentation of 13C labelled quercetin. The addition of inulin, wheat bran or pyrodextrin increased 3,4diOHPAA 2 2.5-fold over 24 h (p < 0.05). Rutin affected SCFA production, but this depended on fibre, fibre concentration and timepoint. With inulin, rutin increased pH at 6 h from 4.9 to 5.6 (p = 0.01) but increased propionic, butyric and isovaleric acid (1.9, 1.6 and 5-fold, p < 0.05 at 24 h). Interactions between fibre and phenolics modify production of phenolic acids and SCFA and may be key in enhancing health benefits.

Lower carbohydrate and higher fat intakes are associated with higher hemoglobin A1c: findings from the UK National Diet and Nutrition Survey 2008-2016.

PURPOSE: Evidence of low-carbohydrate, high-fat diets (LCHF) for type 2 diabetes (T2DM) prevention is scarce. We investigated how carbohydrate intake relates to HbA1c and T2DM prevalence in a nationally representative survey dataset. METHODS: We analyzed dietary information (4-day food diaries) from 3234 individuals aged ≥ 16 years, in eight waves of the UK National Diet and Nutrition Survey (2008-2016). We calculated LCHF scores (0-20, higher score indicating lower  %food energy from carbohydrate, with reciprocal higher contribution from fat) and UK Dietary Reference Value (DRV) scores (0-16, based on UK dietary recommendations). Associations between macronutrients and diet scores and diabetes prevalence were analyzed (in the whole sample) using multivariate logistic regression. Among those without diabetes, analyses between exposures and %HbA1c (continuous) were analyzed using multivariate linear regression. All analyses were adjusted for age, sex, body mass index, ethnicity, smoking status, total energy intake, socioeconomic status and survey years. RESULTS: In the overall study sample, 194 (6.0%) had diabetes. Mean intake was 48.0%E for carbohydrates, and 34.9%E for total fat. Every 5%E decrease in carbohydrate, and every 5%E increase in fat, was associated with 12% (95% CI 0.78-0.99; P = 0.03) and 17% (95% CI 1.02-1.33; P = 0.02) higher odds of diabetes, respectively. Each two-point increase in LCHF score is related to 8% (95% CI 1.02-1.14; P = 0.006) higher odds of diabetes, while there was no evidence for association between DRV score and diabetes. Among the participants without diagnosed diabetes (n = 3130), every 5%E decrease in carbohydrate was associated with higher %HbA1c by + 0.016% (95% CI 0.004-0.029; P = 0.012), whereas every 5%E increase in fat was associated with higher  %HbA1c by + 0.029% (95% CI 0.015-0.043; P < 0.001). Each two-point increase in LCHF score is related to higher  %HbA1c by + 0.010% (0.1 mmol/mol), while each two-point increase in the DRV score is related to lower  %HbA1c by - 0.023% (0.23 mmol/mol). CONCLUSIONS: Lower carbohydrate and higher fat intakes were associated with higher HbA1c and greater odds of having diabetes. These data do not support low(er) carbohydrate diets for diabetes prevention.

Factors influencing the cardiometabolic response to (poly)phenols and phytosterols: a review of the COST Action POSITIVe activities.

PURPOSE: Evidence exists regarding the beneficial effects of diets rich in plant-based foods regarding the prevention of cardiometabolic diseases. These plant-based foods are an exclusive and abundant source of a variety of biologically active phytochemicals, including polyphenols, carotenoids, glucosinolates and phytosterols, with known health-promoting effects through a wide range of biological activities, such as improvements in endothelial function, platelet function, blood pressure, blood lipid profile and insulin sensitivity. We know that an individual's physical/genetic makeup may influence their response to a dietary intervention, and thereby may influence the benefit/risk associated with consumption of a particular dietary constituent. This inter-individual variation in responsiveness has also been described for dietary plant bioactives but has not been explored in depth. To address this issue, the European scientific experts involved in the COST Action POSITIVe systematically analyzed data from published studies to assess the inter-individual variation in selected clinical biomarkers associated with cardiometabolic risk, in response to the consumption of plant-based bioactives (poly)phenols and phytosterols. The present review summarizes the main findings resulting from the meta-analyses already completed. RESULTS: Meta-analyses of randomized controlled trials conducted within POSITIVe suggest that age, sex, ethnicity, pathophysiological status and medication may be responsible for the heterogeneity in the biological responsiveness to (poly)phenol and phytosterol consumption and could lead to inconclusive results in some clinical trials aiming to demonstrate the health effects of specific dietary bioactive compounds. However, the contribution of these factors is not yet demonstrated consistently across all polyphenolic groups and cardiometabolic outcomes, partly due to the heterogeneity in trial designs, low granularity of data reporting, variety of food vectors and target populations, suggesting the need to implement more stringent reporting practices in the future studies. Studies investigating the effects of genetic background or gut microbiome on variability were limited and should be considered in future studies. CONCLUSION: Understanding why some bioactive plant compounds work effectively in some individuals but not, or less, in others is crucial for a full consideration of these compounds in future strategies of personalized nutrition for a better prevention of cardiometabolic disease. However, there is also still a need for the development of a substantial evidence-base to develop health strategies, food products or lifestyle solutions that embrace this variability.

Impact of Foods and Dietary Supplements Containing Hydroxycinnamic Acids on Cardiometabolic Biomarkers: A Systematic Review to Explore Inter-Individual Variability.

Plant-based diets rich in bioactive compounds such as polyphenols have been shown to positively modulate the risk of cardiometabolic (CM) diseases. The inter-individual variability in the response to these bioactives may affect the findings. This systematic review aimed to summarize findings from existing randomized clinical trials (RCTs) evaluating the effect of hydroxycinnamic acids (HCAs) on markers of CM health in humans. Literature searches were performed in PubMed and the Web of Science. RCTs on acute and chronic supplementation of HCA-rich foods/extracts on CM biomarkers were included. Forty-four RCTs (21 acute and 23 chronic) met inclusion criteria. Comparisons were made between RCTs, including assessments based on population health status. Of the 44 RCTs, only seven performed analyses on a factor exploring inter-individual response to HCA consumption. Results demonstrated that health status is a potentially important effect modifier as RCTs with higher baseline cholesterol, blood pressure and glycaemia demonstrated greater overall effectiveness, which was also found in studies where specific subgroup analyses were performed. Thus, the effect of HCAs on CM risk factors may be greater in individuals at higher CM risk, although future studies in these populations are needed, including those on other potential determinants of inter-individual variability. PROSPERO, registration number CRD42016050790.

Effect of ß-Glucan and Black Tea in a Functional Bread on Short Chain Fatty Acid Production by the Gut Microbiota in a Gut Digestion/Fermentation Model.

ß-Glucan and black tea are fermented by the colonic microbiota producing short chain fatty acids (SCFA) and phenolic acids (PA). We hypothesized that the addition of ß-glucan, a dietary fiber, and tea polyphenols to a food matrix like bread will also affect starch digestion in the upper gut and thus further influence colonic fermentation and SCFA production. This study investigated SCFA and PA production from locally developed breads: white bread (WB), black tea bread (BT), ß-glucan bread (ßG), ß-glucan plus black tea bread (ßGBT). Each bread was incubated in an in vitro system mimicking human digestion and colonic fermentation. Digestion with α-amylase significantly (p = 0.0001) increased total polyphenol and polyphenolic metabolites from BT bread compared with WB, ßG, and ßGBT. Total polyphenols in ßGBT remained higher (p = 0.016; 1.3-fold) after digestion with pepsin and pancreatin compared with WB. Fermentations containing ßG and ßGBT produced similar propionate concentrations ranging from 17.5 to 18.6 mmol/L and total SCFA from 46.0 to 48.9 mmol/L compared with control WB (14.0 and 37.4 mmol/L, respectively). This study suggests that combination of black tea with ß-glucan in this functional bread did not impact on SCFA production. A higher dose of black tea and ß-glucan or in combination with other fibers may be needed to increase SCFA production.

Impact of Fermentable Fibres on the Colonic Microbiota Metabolism of Dietary Polyphenols Rutin and Quercetin.

Dietary fibre and polyphenols are both metabolised to short-chain fatty acids (SCFAs) and phenolic acids (PA) by the colonic microbiota. These may alter microbiota growth/diversity, but their interaction is not understood. Interactions between rutin and raftiline, ispaghula or pectin were investigated in human faecal batch cultures (healthy participants; 19⁻33 years, 4 males, 6 females, BMI 18.4⁻27.4) after a low (poly)phenol diet three days prior to study. Phenolic acids were measured by gas chromatography-mass spectrometry and SCFAs by gas chromatography-flame ionisation after 2, 4, 6, and 24 h. Rutin fermentation produced Phenyl acetic acid (PAA), 4-Hydroxy benzoic acid (4-OHBA), 3-Hydroxy phenyl acetic acid (3-OHPAA), 4-Hydroxy phenyl acetic acid (4-OHPAA), 3,4-Dihydroxy phenyl acetic acid (3,4-diOHPAA), 3-Hydroxy phenyl propionic acid (3-OHPPA), and 4-Hydroxy phenyl propionic acid (4-OHPPA). 3,4-DiOHPAA and 3-OHPAA were predominant at 6 h (1.9 ± 1.8 µg/mL, 2.9 ± 2.5 µg/mL, and 0.05 ± 0.0 µg/mL, respectively) and 24 h (5.5 ± 3.3 µg/mL, 3.1 ± 4.2 µg/mL, and 1.2 ± 1.6 µg/mL). Production of all PA except 3-OHPPA and 4-OHPPA was reduced by at least one fibre. Inhibition of PA was highest for rutin (8-fold, p < 0.01), then pectin (5-fold, p < 0.01), and ispaghula (2-fold, p = 0.03). Neither rutin nor quercetin had a detectable impact on SCFA production. These interactions should be considered when assessing dietary polyphenols and potential health benefits.

The urinary phenolic acid profile varies between younger and older adults after a polyphenol-rich meal despite limited differences in in vitro colonic catabolism.

PURPOSE: To investigate whether age influences colonic polyphenol metabolism. METHODS: Healthy participants, younger (n = 8; 23-43 years) and older (n = 13; 51-76 years), followed a 3-day low-polyphenol diet (LPD) and a 3-day high-polyphenol diet (HPD). Urinary phenolic acids (PA), short chain fatty acids (SCFA), pH and gas were monitored, alongside selected colonic bacteria. Human faecal in vitro fermentations of rutin with or without raftiline were used to evaluate the gut microbiota capacity in a subset of both groups. RESULTS: Total urinary PA were higher in the older group after HPD compared to the younger group (1.5-fold; p = 0.04), with no difference between groups in terms of a change between diets (Δ high-low diet). While 17 PA were detected in all younger participants after HPD, a narrower range (n = 8 to 16 PA) was detected in most (n = 9/13) older participants, with lower level of benzoic acid (19-fold; p = 0.03), vanillic acid (4.5-fold; p = 0.04) but higher hippuric acid (2.7-fold; p = 0.03). Faecal SCFA concentration did not change after HPD within group, with similar differential excretion (Δ high-low diet) between groups. There were no differences between groups for faecal pH, total, faecal bacteria including Flavonifractor plautii, bifidobacteria, and bacteroides. In human in vitro faecal fermentations, seven PAs were detected in both groups after 24 h of rutin fermentation, with no quantitative and modest qualitative differences between groups. Total SCFA in faecal fermentation did not differ between groups, except for butyric acid (twofold higher in the older group; p = 0.009) when rutin was fermented with raftiline over 24 h. CONCLUSIONS: Urinary phenolic acids were less diverse in older participants despite limited difference in functional capacity of in vitro faecal fermentations.

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.

High Resolution Mass Spectrometric Analysis of Secoiridoids and Metabolites as Biomarkers of Acute Olive Oil Intake-An Approach to Study Interindividual Variability in Humans.

SCOPE: Phenolic compounds are minor components of extra virgin olive oil (EVOO). Secoiridoids are the major components contributing to the phenolic content of EVOO. Information is lacking regarding their potential as biomarkers for EVOO intake. METHODS AND RESULTS: Healthy volunteers (n = 9) ingested 50 mL of EVOO in a single dose containing 322 mg kg-1 total phenolic content (caffeic acid equivalents) and 6 mg 20 g-1 hydroxytyrosol and its derivatives. Plasma is collected before (0 h) and at 0.5, 1, 2, 4, and 6 h after ingestion. Urine samples are collected prior to ingestion (0 h) and at 0-4, 4-8, 8-15, and 15-24 h. Samples are analyzed by UPLC coupled with an Exactive Orbitrap MS. Partial least squares discriminant analysis with orthogonal signal correction is applied to screen for metabolites that allow sample discrimination. Plasma biomarkers and urine biomarkers are selected although individual variability is observed among volunteers. Results are in accordance with in vitro experiments performed (in vitro digestion and hepatic microsomal activity assays). CONCLUSIONS: Plasma (elenolic acid + H2 ; p-HPEA-EA + H2 + glucuronide) and urinary (3,4-DHPEA-EA, 3,4-DHPEA-EA + H2 +glucuronide, methyl 3,4-DHPEA-EA + H2 +glucuronide) secoiridoid compounds are selected as biomarkers to monitor EVOO intake showing good predictive ability according to multivariate analysis.

The Anti-Adhesive Effect of Curcumin on Candida albicans Biofilms on Denture Materials.

The use of natural compounds as an alternative source of antimicrobials has become a necessity given the growing concern over global antimicrobial resistance. Polyphenols, found in various edible plants, offers one potential solution to this. We aimed to investigate the possibility of using curcumin within the context of oral health as a way of inhibiting and preventing the harmful development of Candida albicans biofilms. We undertook a series of adsorption experiments with varying concentrations of curcumin, showing that 50 µg/ml could prevent adhesion. This effect could be further synergized by the curcumin pre-treatment of yeast cells to obtain significantly greater inhibition (>90%, p < 0.001). Investigation of the biological impact of curcumin showed that it preferentially affected immature morphological forms (yeast and germlings), and actively promoted aggregation of the cells. Transcriptional analyses showed that key adhesins were down-regulated (ALS1 and ALS3), whereas aggregation related genes (ALS5 and AAF1) were up-regulated. Collectively, these data demonstrated that curcumin elicits anti-adhesive effects and that induces transcription of genes integrally involved in the processes related to biofilm formation. Curcumin and associated polyphenols therefore have the capacity to be developed for use in oral healthcare to augment existing preventative strategies for candidal biofilms on the denture surface.

Nutritional intervention and impact of polyphenol on glycohemoglobin (HbA1c) in non-diabetic and type 2 diabetic subjects: Systematic review and meta-analysis.

Polyphenols have been extensively studied for their antioxidant and anti-inflammatory properties. Recently, their antiglycative actions by oxidative stress modulation have been linked to the prevention of diabetes and associated complications. This article assesses the evidence for polyphenol interventions on glycohemoglobin (HbA1c) in non-diabetic, pre-diabetic, and type 2 diabetes mellitus (T2DM) subjects. A systematic review of polyphenols' clinical trials on HbA1c in humans was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis. Thirty-six controlled randomized trials with HbA1c values were included. Polyphenols (extracts, supplements, and foods) were supplemented (28 mg to 1.5 g) for 0.7 to 12 months. Combining all subjects (n = 1954, mean baseline HbA1c = 7.03%, 53 mmol/mol), polyphenol supplementation significantly (P < 0.001) lowered HbA1c% by -0.53 ± 0.12 units (-5.79 ± 0.13 mmol/mol). This reduction was significant (P < 0.001) in T2DM subjects, specifically (n = 1426, mean baseline HbA1c = 7.44%, 58 mmol/mol), with HbA1c% lowered by -0.21 ± 0.04 units (-2.29 ± 0.4 mmol/mol). Polyphenol supplementation had no significant effect (P > 0.21) in the non-diabetic (n = 258, mean baseline HbA1c = 5.47%, 36 mmol/mol) and the pre-diabetic subjects (n = 270, mean baseline HbA1c = 6.06%, 43 mmol/mol) strata: -0.39 ± 0.27 HbA1c% units (-4.3 ± 0.3 mmol/mol), and -0.38 ± 0.31 units (-4.2 ± 0.31 mmol/mol), respectively. In conclusion, polyphenols can successfully reduce HbA1c in T2DM without any intervention at glycemia, and could contribute to the prevention of diabetes complications.

Circulating tumour necrosis factor is highly correlated with brainstem serotonin transporter availability in humans.

Preclinical studies demonstrate that pro-inflammatory cytokines increase serotonin transporter availability and function, leading to depressive symptoms in rodent models. Herein we investigate associations between circulating inflammatory markers and brainstem serotonin transporter (5-HTT) availability in humans. We hypothesised that higher circulating inflammatory cytokine concentrations, particularly of tumour necrosis factor (TNF-α), would be associated with greater 5-HTT availability, and that TNF-α inhibition with etanercept (sTNFR:Fc) would in turn reduce 5-HTT availability. In 13 neurologically healthy adult women, plasma TNF-α correlated significantly with 5-HTT availability (rho=0.6; p=0.03) determined by [(123)I]-beta-CIT SPECT scanning. This association was replicated in an independent sample of 12 patients with psoriasis/psoriatic arthritis (rho=0.76; p=0.003). Indirect effects analysis, showed that there was a significant overlap in the variance explained by 5-HTT availability and TNF-α concentrations on BDI scores. Treatment with etanercept for 6-8weeks was associated with a significant reduction in 5-HTT availability (Z=2.09; p=0.03; r=0.6) consistent with a functional link. Our findings confirm an association between TNF-α and 5-HTT in both the basal physiological and pathological condition. Modulation of both TNF-α and 5-HTT by etanercept indicate the presence of a mechanistic pathway whereby circulating inflammatory cytokines are related to central nervous system substrates underlying major depression.

Selected dietary (poly)phenols inhibit periodontal pathogen growth and biofilm formation.

Periodontitis (PD) is a chronic infectious disease mediated by bacteria in the oral cavity. (Poly)phenols (PPs), ubiquitous in plant foods, possess antimicrobial activities and may be useful in the prevention and management of periodontitis. The objective of this study was to test the antibacterial effects of selected PPs on periodontal pathogens, on both planktonic and biofilm modes of growth. Selected PPs (n = 48) were screened against Streptococcus mitis (S. mitis), Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Fusobacterium nucleatum (F. nucleatum) and Porphyromonas gingivalis (P. gingivalis). The antibacterial potential of each compound was evaluated in terms of planktonic minimum inhibitory concentration (PMIC) and planktonic minimum bactericidal concentration (PMBC) using standardized broth microdilution assays. The most active PPs were further tested for their effect on mono-species and multi-species biofilms using a colorimetric resazurin-based viability assay and scanning electron microscopy. Of the 48 PPs tested, 43 showed effective inhibition of planktonic growth of one or more test strains, of which curcumin was the most potent (PMIC range = 7.8-62.5 µg mL(-1)), followed by pyrogallol (PMIC range = 2.4-2500 µg mL(-1)), pyrocatechol (MIC range = 4.9-312.5 µg mL(-1)) and quercetin (PMIC range = 31.2-500 µg mL(-1)). At this concentration, adhesion of curcumin and quercetin to the substrate also inhibited adhesion of S. mitis, and biofilm formation and maturation. While both curcumin and quercetin were able to alter architecture of mature multi-species biofilms, only curcumin-treated biofilms displayed a significantly reduced metabolic activity. Overall, PPs possess antibacterial activities against periodontopathic bacteria in both planktonic and biofilm modes of growth. Further cellular and in vivo studies are necessary to confirm their beneficial activities and potential use in the prevention and or treatment of periodontal diseases.

Impact of a 6-wk olive oil supplementation in healthy adults on urinary proteomic biomarkers of coronary artery disease, chronic kidney disease, and diabetes (types 1 and 2): a randomized, parallel, controlled, double-blind study.

BACKGROUND: Olive oil (OO) consumption is associated with cardiovascular disease prevention because of both its oleic acid and phenolic contents. The capacity of OO phenolics to protect against low-density lipoprotein (LDL) oxidation is the basis for a health claim by the European Food Safety Authority. Proteomic biomarkers enable an early, presymptomatic diagnosis of disease, which makes them important and effective, but understudied, tools for primary prevention. OBJECTIVE: We evaluated the impact of supplementation with OO, either low or high in phenolics, on urinary proteomic biomarkers of coronary artery disease (CAD), chronic kidney disease (CKD), and diabetes. DESIGN: Self-reported healthy participants (n = 69) were randomly allocated (stratified block random assignment) according to age and body mass index to supplementation with a daily 20-mL dose of OO either low or high in phenolics (18 compared with 286 mg caffeic acid equivalents per kg, respectively) for 6 wk. Urinary proteomic biomarkers were measured at baseline and 3 and 6 wk alongside blood lipids, the antioxidant capacity, and glycation markers. RESULTS: The consumption of both OOs improved the proteomic CAD score at endpoint compared with baseline (mean improvement: -0.3 for low-phenolic OO and -0.2 for high-phenolic OO; P < 0.01) but not CKD or diabetes proteomic biomarkers. However, there was no difference between groups for changes in proteomic biomarkers or any secondary outcomes including plasma triacylglycerols, oxidized LDL, and LDL cholesterol. CONCLUSION: In comparison with low-phenolic OO, supplementation for 6 wk with high-phenolic OO does not lead to an improvement in cardiovascular health markers in a healthy cohort.

Utilising polyphenols for the clinical management of Candida albicans biofilms.

Polyphenols (PPs) are secondary metabolites abundant in plant-derived foods. They are reported to exhibit antimicrobial activity that may offer an alternative to existing antimicrobials. The aim of this study was to evaluate the antifungal potential of PPs against Candida albicans biofilms that are commonly recalcitrant to antifungal therapy. The antifungal activity of 14 PPs was assessed in terms of planktonic and sessile minimum inhibitory concentrations (PMICs and SMICs, respectively) against various C. albicans clinical isolates. The most active PPs were further tested for their effect on C. albicans adhesion and biofilm growth using standard biomass assays, microscopy and quantitative gene expression. Of the 14 PPs tested, 7 were effective inhibitors of planktonic growth, of which pyrogallol (PYG) was the most effective (PMIC50=78 µg/mL), followed by curcumin (CUR) (PMIC50=100 µg/mL) and pyrocatechol (PMIC50=625 µg/mL). Both PYG and CUR displayed activity against C. albicans biofilms (SMIC50=40 µg/mL and 50 µg/mL, respectively), although they did not disrupt the biofilm or directly affect the cellular structure. Overall, CUR displayed superior biofilm activity, significantly inhibiting initial cell adhesion following pre-coating (P<0.01), biofilm growth (P<0.05) and gene expression (P<0.05). This inhibitory effect diminished with prolonged CUR exposure, although it still inhibited by 50% after 4h adhesion. Overall, CUR exhibited positive antibiofilm properties that could be used at the basis for development of similar molecules, although further cellular and in vivo studies are required to explore its precise mechanism of action.

Oxidative stress, protein glycation and nutrition--interactions relevant to health and disease throughout the lifecycle.

Protein glycation has been studied for over a century now and plays an important role in disease pathogenesis throughout the lifecycle. Strongly related to diabetic complications, glycation of Hb has become the gold standard method for diabetes diagnosis and monitoring. It is however attracting attention in normoglycaemia as well lately. Longitudinal studies increasingly suggest a positive relationship between glycation and the risk of chronic diseases in normoglycaemic individuals, but the mechanisms behind this association remain unclear. The interaction between glycation and oxidative stress may be particularly relevant in the normoglycaemic context, as suggested by recent epidemiological and in vitro evidence. In that context nutritional and lifestyle factors with an influence on redox status, such as smoking, fruit and vegetable and antioxidants consumption, may have the capacity to promote or inhibit glycation. However, experimental data from controlled trials are lacking the quality and rigour needed to reach firm conclusions. In the present review, we discuss the importance of glycation for health through the lifecycle and focus on the importance of oxidative stress as a driver for glycation. The importance of nutrition to modulate glycation is discussed, based on the evidence available and recommendations towards higher quality future research are made.