Vitamin B6 Pathway Maintains Glioblastoma Cell Survival in 3D Spheroid Cultures.

Glioblastoma (GBM) is a deadly brain cancer. The prognosis of GBM patients has marginally improved over the last three decades. The response of GBMs to initial treatment is inevitably followed by relapse. Thus, there is an urgent need to identify and develop new therapeutics to target this cancer and improve both patient outcomes and long-term survival. Metabolic reprogramming is considered one of the hallmarks of cancers. However, cell-based studies fail to accurately recapitulate the in vivo tumour microenvironment that influences metabolic signalling and rewiring. Against this backdrop, we conducted global, untargeted metabolomics analysis of the G7 and R24 GBM 2D monolayers and 3D spheroid cultures under identical cell culture conditions. Our studies revealed that the levels of multiple metabolites associated with the vitamin B6 pathway were significantly altered in 3D spheroids compared to the 2D monolayer cultures. Importantly, we show that pharmacological intervention with hydralazine, a small molecule that reduces vitamin B6 levels, resulted in the cell death of 3D GBM spheroid cultures. Thus, our study shows that inhibition of the vitamin B6 pathway is a novel therapeutic strategy for the development of targeted therapies in GBMs.

Mixed Tree Nuts, Cognition, and Gut Microbiota: A 4-Week, Placebo-Controlled, Randomized Crossover Trial in Healthy Nonelderly Adults.

BACKGROUND: Beneficial effects of nut supplementation on cognitive function have previously been demonstrated in young and older adults. Alterations to gut microbiota have also been shown following tree nut consumption. However, no data exists on the effects of nuts on cognition and intestinal microbial communities assessed within the same study. OBJECTIVES: The study aimed to examine the effects of daily consumption of tree nuts for 4 wk on cognitive function (primary outcome), mood, metabolomics, and gut microbial species (secondary outcomes) in healthy, nonelderly adults. METHODS: This randomized, placebo-controlled, double-blind, counterbalanced crossover study assessed the effects of 4 wk of supplementation with 30 g/d mixed tree nuts versus placebo on cognition and mood in 79 healthy adults aged 18-49 y. Metabolic responses, gut bacterial community structure, and the potential for these to impact cognition were explored using a multi-omic approach. Bacterial community analysis was conducted in Quantitative Insights Into Microbial Ecology 2 (QIIME2). RESULTS: Mixed model analysis indicated that nut consumption led to significant improvements to accuracy (placebo M = 92.2% compared with NUTS M = 94.5%; P = 0.019) and speed of response (placebo M = 788 ms compared with NUTS M = 757 ms; P = 0.004) on a picture recognition task. No significant changes to bacterial community α or ß diversity were observed when comparing nut consumption to the placebo arm. However, an unclassified Lachnospiraceae amplicon sequence variant (ASV) was significantly enriched in participants when supplemented with nuts (P = 0.015). No correlations were observed between the changes to picture recognition and the changes to the unclassified Lachnospiraceae ASV. There were no significant changes to the urinary metabolome. CONCLUSIONS: These findings indicate a positive effect of nut on cognition following only 4 wk of consumption in a healthy nonelderly sample, as well as upregulation of a microbial taxa associated with gut health. The effects appear to be independent of one another, but further exploration is required in those experiencing cognitive decline and/or gut dysbiosis.

Associations between free sugar intake and markers of health in the UK population: an analysis of the National Diet and Nutrition Survey rolling programme.

Recommendations for free sugar intake in the UK should be no more than 5 % of total energy due to increased health risks associated with overconsumption. It was therefore of interest to examine free sugar intakes and associations with health parameters in the UK population. The UK National Diet and Nutrition Survey rolling programme (2008-2017) was used for this study. Dietary intake, anthropometrical measurements and clinical biomarker data collated from 5121 adult respondents aged 19-64 years were statistically analysed. Compared with the average total carbohydrate intake (48 % of energy), free sugars comprised 12·5 %, with sucrose 9 % and fructose 3·5 %. Intakes of these sugars, apart from fructose, were significantly different over collection year (P < 0·001) and significantly higher in males (P < 0·001). Comparing those consuming above or below the UK recommendations for free sugars (5 % energy), significant differences were found for BMI (P < 0·001), TAG (P < 0·001), HDL (P = 0·006) and homocysteine concentrations (P = 0·028), and significant sex differences were observed (e.g. lower blood pressure in females). Regression analysis demonstrated that free sugar intake could predict plasma TAG, HDL and homocysteine concentrations (P < 0·0001), consistent with the link between these parameters and CVD. We also found selected unhealthy food choices (using the UK Eatwell Guide) to be significantly higher in those that consumed above the recommendations (P < 0·0001) and were predictors of free sugar intakes (P < 0·0001). We have shown that adult free sugar intakes in the UK population are associated with certain negative health parameters that support the necessary reduction in free sugar intakes for the UK population.

Polyphenol-rich tart cherries (Prunus Cerasus, cv Montmorency) improve sustained attention, feelings of alertness and mental fatigue and influence the plasma metabolome in middle-aged adults: a randomised, placebo-controlled trial.

Tart Montmorency cherries (MC) are a particularly rich source of anthocyanins and other polyphenols that have been shown to elicit antioxidant, anti-inflammatory and vasomodulatory actions. The current study aimed to determine the influence of chronic MC supplementation on cognitive function and mood. In a 3-month double-blinded, placebo-controlled parallel study, middle-aged adults (mean ± sd: 48 ± 6 years) were randomly assigned to either 30 ml twice daily of MC (n 25) or the same amount of an isoenergetic placebo (n 25). Cognitive function and mood were assessed before and after supplementation using a computerised cognitive task battery and visual analogue scales. Cerebral blood flow was also monitored by near-infrared spectroscopy during the task battery, and questionnaires were administered to determine subjective sleep and health status and plasma metabolomics were analysed before and after supplementation. After 3 months, the MC resulted in higher accuracy in digit vigilance (mean difference: 3·3, 95 % CI: 0·2, 6·4 %) with lower number of false alarms (mean difference: -1·2, 95 % CI: -2·0, -0·4) compared with the placebo. There was also a treatment effect for higher alertness (mean difference: 5·9, 95 % CI: 1·3, 10·5 %) and lower mental fatigue ratings (mean difference -9·5, 95 % CI: -16·5, -2·5 %) with MC. Plasma metabolomics revealed an increase in a number of amino acids in response to MC intake, but not placebo. These data suggest an anti-fatiguing effect of MC supplementation as well as the ability to improve sustained attention during times of high cognitive demand, this could be related to changes in amino acid metabolism.

Effects of chronic consumption of specific fruit (berries, citrus and cherries) on CVD risk factors: a systematic review and meta-analysis of randomised controlled trials.

PURPOSE: This review aims to compare the magnitude of the effects of chronic consumption of fruits; specifically berries, citrus and cherries on cardiovascular disease (CVD) risk factors. METHODS: PubMed, Web of Science, Scopus, and psycARTICLES were searched from inception until January 2020. Forty-five chronic (≥ 1 week) randomised controlled trials assessing CVD risk factors including endothelial (dys)function, blood pressure (BP), blood lipids and inflammatory biomarkers were included. RESULTS: Investigated interventions reported improvements in endothelial function (n = 8), inflammatory biomarkers and lipid status (n = 14), and BP (n = 10). Berries including juice of barberry, cranberry, grape, pomegranate, powder of blueberry, grape, raspberry and freeze-dried strawberry significantly reduced SBP by 3.68 mmHg (95% CI - 6.79 to - 0.58; P = 0.02) and DBP by 1.52 mmHg (95% CI - 2.87 to - 0.18, P = 0.04). In subgroup analysis, these associations were limited to cranberry juice (SBP by 1.52 mmHg [95% CI - 2.97 to - 0.07; P = 0.05], DBP by 1.78 mmHg [95% CI - 3.43 to - 0.12, P = 0.04] and cherry juice (SBP by 3.11 mmHg [95% CI - 4.06 to - 2.15; P = 0.02]). Berries also significantly elevated sVCAM-1 levels by 14.57 ng/mL (85% CI 4.22 to 24.93; P = 0.02). CONCLUSION: These findings suggest that supplementing cranberry or cherry juice might contribute to an improvement in blood pressure. No other significant improvements were observed for other specified fruits. More research is warranted comparing different classes of fruit and exploring the importance of fruit processing on their cardiovascular-protective effects.

Dietary intake of anthocyanins and risk of cardiovascular disease: A systematic review and meta-analysis of prospective cohort studies.

Accumulating evidence suggests flavonoid intake is associated with reduced risk of non-communicable diseases. We aimed to systematically determine and quantify the potential association between dietary anthocyanin intake and risk of cardiovascular diseases (CVD). A systematic literature search of studies reporting anthocyanin intake and risk of fatal or nonfatal CVD was performed using SCOPUS, MEDLINE, CINAHL and Cochrane Library. The relative risk (RR) or hazard ratio (HR) of highest category of anthocyanin foods were pooled in a random-effects meta-analysis. Subgroup analysis were conducted to determine possible sources of heterogeneity. The meta-analysis suggested intake of dietary anthocyanins and reduced risk of CHD (RR = 0.91, 95% CI: 0.83, 0.99; I2 = 12.0, Ph = 0.337) and CVD mortality (RR = 0.92, 95% CI: 0.87, 0.97; I2 = 0.0, Ph = 0.584). However, there was no relationship between the intake of these compounds and reduced risk of MI, stroke or total CVD. Subgroup analysis determined reduced risk of CHD and CVD mortality was more prominent for anthocyanidin intake, as opposed to anthocyanin or berries. Our systematic review and meta-analysis provides evidence that anthocyanins, specifically anthocyanidins, reduce the risk of CHD and CVD mortality. Further randomized controlled trials on anthocyanin intake and CVD risk factors are needed to support these findings.

Lycopene and tomato and risk of cardiovascular diseases: A systematic review and meta-analysis of epidemiological evidence.

BACKGROUND AND AIMS: Worldwide, cardiovascular diseases (CVDs) remains as the main cause of mortality. Observational studies supports an association between intake of tomato products or lycopene with a reduced CVDs risk. Our aim was to undertake a systematic review and meta-analysis of the evidence on the topic. METHODS: Medline, Web of Science, and Scopus were searched from inception until July 2017. We included longitudinal and cross-sectional studies reporting associations between lycopene and tomato consumption and cardiovascular morbidity and mortality among adult subjects. Random-effects models were used to determine the pooled effect sizes. RESULTS: Twenty-eight publications met our inclusion criteria and 25 studies provided quantitative data for meta-analysis. Results showed that individuals in the highest consumption category of, or with the highest serum concentration of, lycopene had significantly lower risk of stroke (hazard ratio (HR) 0.74, 0.62-0.89, p = 0.02; I2 = 32) and CVDs (HR 0.86, 0.77-0.95, p = 0.003; I2 = 0). In addition, individuals categorised in the highest serum concentration of lycopene also had significantly lower risk of mortality (HR 0.63, 0.49-0.81, p<0.001; I2 = 46). Lycopene was not significantly associated with myocardial infarction, while scarce evidence on the association of lycopene with atherosclerosis, congestive heart failure, or atrial fibrillation was evident. Evidence from three studies suggested that higher intakes of tomato were associated with non-significantly lower stroke, CVDs and CHD. CONCLUSIONS: This comprehensive meta-analysis suggests that high-intakes or high-serum concentration of lycopene are associated with significant reductions in the risk of stroke (26%), mortality (37%) and CVDs (14%).

Methodological Considerations for a Vascular Function Test Battery.

There is a dearth of information regarding the reliability of non-invasive measures of vascular function taken in a single testing session. This study aimed to determine the test-retest reliability of a test battery of vascular function measures: automated blood pressure (BP), laser Doppler imaging with iontophoresis (LDI), digital volume pulse (DVP), pulse wave velocity (PWV), augmentation index (AIx) measured by pulse wave analysis (PWA) and flow-mediated dilation (FMD) taken within and between sessions. Measures were taken in 21 non-smoking males intra-session and again inter-session (one week apart) to determine repeatability and reproducibility, respectively. There was moderate to excellent repeatability (ICC: 0.53-0.93; CV=2.2-18.1%) and reproducibility (ICC: 0.71-0.96; CV 1.9-14.2%) for BP, DVP stiffness index, PWV, AIx, AIx normalised to heart rate (75 bpm), absolute and percentage FMD. Repeatability of the DVP reflection index was moderate (ICC: 0.64; CV=9.5%) but there was poor reproducibility (ICC: 0.17; CV=15.1%). Moreover, the repeatability and reproducibility of the LDI measures ranged from poor to good (ICC: 0.31-0.84; CV=28.4-36.7%). These data indicated that there was considerable variability in the repeatability and reproducibility of measurements of endothelial function and arterial stiffness taken in a battery of measurements, which needs careful consideration in future research designs.

The influence of juicing on the appearance of blueberry metabolites 2 h after consumption: a metabolite profiling approach.

The consumption of berries has been linked to decreased risk of degenerative disease. Berries are regularly processed into juices. It is largely unknown how the juicing process affects the bioavailability of metabolites. As metabolomics has shown to be a valuable nutritional tool to study global metabolite differences, the aim of this study was to investigate the effect of juicing on the relative appearance of blueberry metabolites in humans using metabolomics. Nine healthy subjects consumed 250 g of fresh blueberries either as the whole fruit or after juicing, and provided blood and urine samples before and 2 h after intake in a cross-over design. Samples underwent metabolite profiling using LCMS, and data were mined with multivariate analysis. Overall, <12 % of all ions detected were significantly influenced by blueberry treatment (P<0·05). Partial least-squared discriminant analysis models of post-treatment samples revealed good discrimination. In urinary samples, whole blueberry treatment resulted in 108 ions that were significantly higher compared with juiced treatment (positive and negative mode combined), whereas only eight were significantly higher after juiced treatment. Examples of putative annotations included metabolites of ferulic and caffeic acids, several phenolic metabolites conjugated to sulphate, glycoside or glucuronide and fatty acyl derivatives, which were of higher intensity after whole blueberry treatment. In conclusion, consumption of whole blueberries resulted in a higher range of phenolic and other metabolites in plasma and urine samples 2 h after consumption. Both whole and juiced blueberries resulted in very similar metabolite profiles at 2 h, although this was the only time point measured.

Phytochemical uptake following human consumption of Montmorency tart cherry (L. Prunus cerasus) and influence of phenolic acids on vascular smooth muscle cells in vitro.

PURPOSE: To investigate the phytochemical uptake following human consumption of Montmorency tart cherry (L. Prunus cerasus) and influence of selected phenolic acids on vascular smooth muscle cells in vitro. METHODS: In a randomised, double-blinded, crossover design, 12 healthy males consumed either 30 or 60 mL of Montmorency tart cherry concentrate. Following analysis of the juice composition, venous blood samples were taken before and 1, 2, 3, 5 and 8 h post-consumption of the beverage. In addition to examining some aspects of the concentrate contents, plasma concentrations of protocatechuic acid (PCA), vanillic acid (VA) and chlorogenic (CHL) acid were analysed by reversed-phase high-performance liquid chromatography (HPLC) with diode array for quantitation and mass spectrometry detection (LCMS) for qualitative purposes. Vascular smooth muscle cell migration and proliferation were also assessed in vitro. RESULTS: Both the 30 and 60 mL doses of Montmorency cherry concentrate contained high amounts of total phenolics (71.37 ± 0.11; 142.73 ± 0.22 mg/L) and total anthocyanins (62.47 ± 0.31; 31.24 ± 0.16 mg/L), as well as large quantities of CHL (0.205 ± 0.24; 0.410 ± 0.48 mg/L) and VA (0.253 ± 0.84; 0.506 ± 1.68 mg/L). HPLC/LCMS identified two dihydroxybenzoic acids (PCA and VA) in plasma following MC concentrate consumption. Both compounds were most abundant 1-2 h post-initial ingestion with traces detectable at 8 h post-ingestion. Cell migration was significantly influenced by the combination of PCA and VA, but not in isolation. There was no effect of the compounds on cell proliferation. CONCLUSIONS: These data show new information that phenolic compounds thought to exert vasoactive properties are bioavailable in vivo following MC consumption and subsequently can influence cell behaviour. These data may be useful for the design and interpretation of intervention studies investigating the health effects of Montmorency cherries.

Inter-Individual Responses to a Blueberry Intervention across Multiple Endpoints.

Inter-individual variation exists in response to diet and in the endpoints related to vascular diseases and cognitive impairment. Therefore, the evaluation and characterisation of responses to a dietary intervention targeting these endpoints is important. A dietary intervention with 37 participants has been performed comparing two forms of blueberry, either whole fresh blueberry (160 g), freeze-dried blueberry powder (20 g) or a placebo control (microcrystalline cellulose), in a 1-week single-blinded cross-over randomised controlled trial (RCT) in a healthy population. The response to the intervention was calculated for each endpoint using the percentage change (±%) compared to the baseline. Extensive inter-individual variation was found in vascular health parameters (-141 to +525%) and cognitive domains (-114 to +96%) post-intervention, but there was no consistent response following the two interventions between and within participants for each endpoint measured. No significant putative discriminating urinary metabolites between interventions were found using supervised multivariate analysis. Although several discriminatory metabolites were found between the responder and non-responder groups, it was not possible to identify predictors of the response using receiver operating curve analysis. To conclude, this is the first blueberry intervention applying quartile divisions to characterise individual responses in vascular and cognitive endpoints following a specific dietary intervention; however, we did not find any consistency in the individual responses to the interventions, and we could not identify a predictive urinary metabolite as a potential biomarker for differentiation between responders and non-responders. However, the overall approach of defining a metabolic signature of response could be used in the future for tailored personalised nutritional advice.

Effects of chronic consumption of specific fruit (berries, cherries and citrus) on cognitive health: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: The cognitive-protective effects related to the consumption of a variety of fruits are supported by several intervention studies. This systematic review and meta-analysis compared the magnitude of effects following chronic (≥1 week) consumption of frozen, freeze-dried powder including extracts and juices of fruits, covering berries, cherries and citrus, on cognition and mood in adults. METHODS: PubMed, Web of Science, Scopus, and psycARTICLES were searched from inception until February, 2021. Inclusion criteria were randomised controlled trials assessing memory, executive function, psychomotor speed, mood and mini mental state examination in adult participants ≥18 years of age. Cognition was tested by global or domain specific tasks. RESULTS: Out of 13,861 articles identified, 16 papers were included; 11 studies provided suitable data for meta-analysis. Fourteen studies reported improvement or trend for improvement in cognition, five studies assessed mood and one study supplementing grape juice found trend for mood improvement. From the meta-analysis, cherry juice supplementation was suggested to improve psychomotor speed by -0.37 of standardised mean difference (95% CI [-0.74, 0.01]) in reaction time (P = 0.05). CONCLUSIONS: The meta-analysis did not sufficiently support a role for fruits or fruit forms to improve cognition and mood.

Effects of Blueberry Consumption on Cardiovascular Health in Healthy Adults: A Cross-Over Randomised Controlled Trial.

Blueberries are rich in polyphenols, and their effect on cardiovascular health, including risk factors for endothelial dysfunction and hypertension, has been investigated in interventional studies. However, the difference between blueberry treatments in varied forms for their cardiovascular-protective effect remains poorly understood. The current study assessed the effects of whole blueberry and freeze-dried blueberry powder compared to a control on cardiovascular health in young adults. A cross-over randomised controlled trial (RCT) was implemented with 1 week of treatment for three treatment groups, each followed by 1 week of wash out period. Systolic (SBP) and diastolic blood pressure (DBP), pulse wave velocity (PWV), plasma cholesterol (low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total cholesterol) and triglyceride levels (TAG), and glucose and nitrite (NO2-) concentrations were compared following fresh blueberry, freeze-dried blueberry powder, and control treatments. Thirty-seven participants with a mean age of 25.86 ± 6.81 completed the study. No significant difference was observed among fresh blueberry, blueberry powder, and the control arm. Plasma NO2- levels were improved by 68.66% and 4.34% separately following whole blueberry and blueberry powder supplementations compared to the baseline, whereas the control supplementation reported a decrease (-9.10%), although it was not statistically significant. There were no other effects shown for SBP, DBP, total cholesterol, HDL-C, LDL-C, TAG, or glucose. No difference was shown between whole blueberry and freeze-dried blueberry powder consumption for improving cardiovascular health.

Metabolomics and human nutrition.

The present report summarises a workshop convened by the UK Food Standards Agency (Agency) on 25 March 2010 to discuss the current Agency's funded research on the use of metabolomics technologies in human nutrition research. The objectives of this workshop were to review progress to date, to identify technical challenges and ways of overcoming them, and to discuss future research priorities and the application of metabolomics in public health nutrition research and surveys. Results from studies nearing completion showed that by using carefully designed dietary and sampling regimens, it is possible to identify novel biomarkers of food intake that could not have been predicted from current knowledge of food composition. These findings provide proof-of-principle that the metabolomics approach can be used to develop new putative biomarkers of dietary intake. The next steps will be to validate these putative biomarkers, to develop rapid and inexpensive assays for biomarkers of food intake of high public health relevance, and to test their utility in population cohort studies and dietary surveys.

Determination of selected water-soluble vitamins (thiamine, riboflavin, nicotinamide and pyridoxine) from a food matrix using hydrophilic interaction liquid chromatography coupled with mass spectroscopy.

Water-soluble vitamins are essential dietary components with a multitude of important functions that require quantification from food sources to characterise the nutritional status of food. In this study, we have developed a hydrophilic interaction chromatography (HILIC) based method coupled to single-quadrupole mass spectrometry (MS) for the analysis of selected water-soluble vitamins. Due to their involvement in energy release from macronutrients, the quantification of thiamine (B1), riboflavin (B2), nicotinamide (B3) and pyridoxine (B6) offers significant value in food analysis. A commercially available vegetable soup was selected as the food matrix for this study and utilised to develop an efficient extraction procedure for the vitamins of interest. Vitamins were extracted using meta-phosphoric acid coupled with a reducing agent, DL-dithiothreitol (DTT) to produce the parent compound. The extracted vitamins were then analysed using an LC-MS system with electrospray - atmospheric pressure ionization (ES-API) source, operated in positive single ion monitoring (SIM) mode. The MS provided good linearity within the investigated range from 5 to 400 ng/mL with coefficient of determination (r2) ranging from 0.98 to 0.99. Retention times (0.65-9.04 min) were reproducible and no coelution between vitamins was observed. Limit of detection (LOD) varied from 2.4 to 9.0 ng/mL and limit of quantification (LOQ) was from 8 to 30 ng/mL, comparable to previously published studies. The extraction method provided good intra-day (%CV 1.56-6.56) and inter-day precision (%CV 8.07-10.97). Standard injections were used as part of quality control measures and provided excellent reproducibility (%CV 0.9-3.4). The overall runtime of this method was 19 min, including column reconditioning. Using this method, the quantity of thiamine (67 ±â€¯7 ng/g), riboflavin (423 ±â€¯39 ng/g), nicotinamide (856 ±â€¯77 ng/g) and pyridoxine (133 ±â€¯11 ng/g) was determined from a complex food matrix. In conclusion, we have developed a rapid and reliable, HILIC-single quad MS method utilising SIM for the low-level quantification of four B vitamins in a vegetable soup matrix in under 20 min. This method has shown excellent linearity, intra- and inter-day reproducibility and is directly applicable to other plant-based food matrices.

A pilot feasibility study investigating the impact of increasing sucrose intakes on body composition and blood pressure.

Epidemiological and intervention studies have reported negative health effects of sucrose intake, but many of these studies were not representative of typical dietary habits. In this pilot study, we aimed to test the effect of increasing sucrose intakes for 1 week on body composition and blood pressure and explore the feasibility of consuming high intakes of sucrose in addition to a habitual diet. In a randomised crossover design study, twelve healthy participants (50 % female, age 28⋅4 ± 10 years, BMI 25 ± 3 kg/m2), consumed either 40, 80 or 120 g sucrose in 500 ml water in addition to their habitual diet every day for 1 week, with a 1-week washout between treatment periods. Body composition (assessed using bioelectrical impedance) and blood pressure measurements were taken before and after each intervention phase. All participants reported no issues with consuming the sucrose dose for the intervention period. There was a significant increase in systolic blood pressure following 120 g sucrose intake (P = 0⋅006), however there was no significant changes to blood pressure, body weight, BMI, percentage protein, fat or water (P > 0⋅05) when comparing change from baseline values. There was also no effect of sucrose intakes on energy or macronutrient intakes during the intervention (P > 0⋅05). We show here that varying doses of sucrose over a 1-week period have no effect on body composition or blood pressure. The amounts of sucrose used were an acceptable addition to the habitual diet and demonstrate the feasibility of larger-scale studies of chronic sucrose supplementation.

The Influence of Tart Cherry (Prunus cerasus, cv Montmorency) Concentrate Supplementation for 3 Months on Cardiometabolic Risk Factors in Middle-Aged Adults: A Randomised, Placebo-Controlled Trial.

BACKGROUND: Tart Montmorency cherries (MC) have been shown to be rich in anthocyanins and other phytochemicals known to have anti-inflammatory properties and influence pathways that might improve cardiometabolic health. However, there is limited evidence for the longer-term use of tart cherries on these indices. The aim of the current study was to investigate the influence of MC concentrate on cardiometabolic health indices following a 3-month supplementation period. METHODS: Fifty middle-aged adults (34 males and 16 females; mean ± SD age: 48 ± 6 years and BMI: 27.6 ± 3.7 kg/m2) completed a randomised, placebo-controlled parallel study in which they either received MC or an isocaloric placebo. Participants drank 30 mL of their allocated treatment twice per day for 3 months. Vascular function (blood pressure [BP], heart rate [HR], pulse wave velocity and analysis [PWV/A], and flow mediated dilation [FMD]) as well as indices of metabolic health (insulin, glucose, lipid profiles, and high sensitivity C reactive protein) were measured following an overnight fast before and after the 3 months. RESULTS: No effect of the intervention between the groups was observed for vascular function or metabolic health variables following the intervention (p > 0.05). However, MC concentrate was shown to be safe and well-tolerated and, importantly, did not have any deleterious effects on these outcomes. In conclusion, MC has no influence on cardiometabolic indices in middle-aged adults.

The influence of tart cherries (Prunus Cerasus) on vascular function and the urinary metabolome: a randomised placebo-controlled pilot study.

Montmorency tart cherries (MC) have been found to modulate indices of vascular function with interventions of varying duration. The objective of this preliminary study was to identify the chronic effects of MC supplementation on vascular function and the potential for urinary metabolomics to provide mechanistic evidence. We performed a placebo-controlled, double-blind, randomised study on 23 healthy individuals (18M, 7F) that consumed 30 ml MC or a placebo twice daily for 28 days. Whole body measures of vascular function and spot urine collections were taken at baseline and after supplementation. There were no significant changes to vascular function including blood pressure and arterial stiffness. Urinary metabolite profiling highlighted significant changes (P < 0⋅001) with putative discriminatory metabolites related to tryptophan and histidine metabolism. Overall, MC supplementation for 28 days does not improve indices of vascular function but changes to the urinary metabolome could be suggestive of potential mechanisms.

The Impact of NOD2 Genetic Variants on the Gut Mycobiota in Crohn's Disease Patients in Remission and in Individuals Without Gastrointestinal Inflammation.

BACKGROUND AND AIMS: Historical and emerging data implicate fungi in Crohn's disease [CD] pathogenesis. However, a causal link between mycobiota, dysregulated immunity, and any impact of NOD2 variants remains elusive. This study aims to evaluate associations between NOD2 variants and faecal mycobiota in CD patients and non-CD subjects. METHODS: Faecal samples were obtained from 34 CD patients [18 NOD2 mutant, 16 NOD2 wild-type] identified from the UK IBD Genetics Consortium. To avoid confounding influence of mucosal inflammation, CD patients were in clinical remission and had a faecal calprotectin <250 µg/g; 47 non-CD subjects were included as comparator groups, including 22 matched household [four NOD2 mutant] and 25 non-household subjects with known NOD2 genotype [14 NOD2 mutant] identified by the NIHR BioResource Cambridge. Faecal mycobiota composition was determined using internal transcribed spacer 1 [ITS1] sequencing and was compared with 16S rRNA gene sequences and volatile organic compounds. RESULTS: CD was associated with higher numbers of fungal observed taxonomic units [OTUs] [p = 0.033]. Principal coordinates analysis using Jaccard index [p = 0.018] and weighted Bray-Curtis dissimilarities [p = 0.01] showed Candida spp. clustered closer to CD patients whereas Cryptococcus spp. clustered closer to non-CD. In CD, we found higher relative abundance of Ascomycota [p = 0.001] and lower relative abundance Basidiomycota [p = 0.019] phyla. An inverse relationship was found between bacterial and fungal Shannon diversity in NOD2 wild-type which was independent of CD [r = -0.349; p = 0.029]. CONCLUSIONS: This study confirms compositional changes in the gut mycobiota in CD and provides evidence that fungi may play a role in CD pathogenesis. No NOD2 genotype-specific differences were observed in the faecal mycobiota.