Factors Associated with Low Vitamin D Status among Older Adults in Kuwait.

Low vitamin D levels among older people represent a significant health problem worldwide. This study aimed to examine the factors associated with vitamin D deficiency in older people (aged ≥ 65) in the Kuwaiti population. A cross-sectional study was conducted in seven primary healthcare centers across Kuwait (November 2020 to June 2021). The participants (n = 237) had their serum vitamin D (25(OH)D) concentrations (analyzed using LC-MS) classified as sufficiency 75 nmol/L (30 ng/mL) or deficiency < 75 nmol/L (below 30 ng/mL). The data were collected using self-administered questionnaires and face-to-face interviews with participants in geriatric clinics. Binomial logistic regression analysis was applied to assess factors associated with vitamin D deficiency. Vitamin D deficiency was found to be present in two thirds of the participants (n = 150, 63%), with a higher prevalence of deficiency in participants who did not receive vitamin D supplements, compared to those who did (84% vs. 16%, p = 0.001). The results from the binary logistic regression showed that a low duration of sun exposure (OR = 0.24, 95% C.I. [0.08−0.7], p = 0.011), dark skin pigmentation (OR = 4.46, 95% [1.35−20.49], p = 0.026), and lower caloric intake (OR = 0.9, 95% C.I. [0.85−0.96], p = 0.001) were risk factors for vitamin D deficiency. Furthermore, a significant inverse relationship was found between vitamin D levels and parathyroid hormone (PTH) levels (OR = 1.16, 95% C.I. [1.04−1.31], p = 0.016). These findings support the recommendation that vitamin D supplementation and adequate sunlight exposure are necessary for raising low vitamin D levels in older people in Kuwait.

Grape seed polyphenol extract and cognitive function in healthy young adults: a randomised, placebo-controlled, parallel-groups acute-on-chronic trial.

Grapes are polyphenol-rich, and grape juice intake has shown cognitive benefits in middle-aged females and older adults with mild cognitive impairment. Extracts obtained from grape seeds have similarly been associated with cognitive benefits in older adults. The aim of this research was to investigate whether a highly purified grape seed-derived polyphenol extract was associated with cognitive benefits in healthy young adults following a single acute dose, and chronically following repeated daily dosage over 12 weeks. Following an acute-on-chronic, parallel groups, randomised, double-blind, placebo-controlled design, sixty adults aged 18-30 consumed either a 400 mg grape seed polyphenol extract (GSPE, n = 30) or a placebo (n = 30). Cognitive function was assessed acutely at baseline and 2, 4 and 6 h post consumption, and chronically at 6 and 12 twelve weeks with a computerised battery of multiple cognitive tests. Mood was assessed with the Positive and Negative Affect Schedule. Linear marginal model analysis with baseline included as a covariate did not reveal a consistent pattern of cognitive benefits following the GSPE relative to the placebo either acutely or chronically when considering all outcome measures. GSPE was associated with some improvements in reaction time (acutely) and psychomotor skill (chronically), however the placebo was also associated with some benefits to reaction time and memory. Therefore, a 400 mg GSPE did not consistently improve cognitive function in healthy young adults. These findings suggest that younger, healthy populations are perhaps less sensitive to polyphenol extract doses <400mg relative to older, or cognitively compromised populations.

Anthocyanins Promote Learning through Modulation of Synaptic Plasticity Related Proteins in an Animal Model of Ageing.

Anthocyanin-rich foods, such as berries, reportedly ameliorate age-related cognitive deficits in both animals and humans. Despite this, investigation into the mechanisms which underpin anthocyanin-mediated learning and memory benefits remains relatively limited. The present study investigates the effects of anthocyanin intake on a spatial working memory paradigm, assessed via the cross-maze apparatus, and relates behavioural test performance to underlying molecular mechanisms. Six-week supplementation with pure anthocyanins (2% w/w), administered throughout the learning phase of the task, improved both spatial and psychomotor performances in aged rats. Behavioural outputs were accompanied by changes in the expression profile of key proteins integral to synaptic function/maintenance, with upregulation of dystrophin, protein kinase B (PKB/Akt) and tyrosine hydroxylase, and downregulation of apoptotic proteins B-cell lymphoma-extra-large (Bcl-xL) and the phosphorylated rapidly accelerated fibrosarcoma (p-Raf). Separate immunoblot analysis supported these observations, indicating increased activation of extracellular signal-related kinase (ERK1), Akt Ser473, mammalian target of rapamycin (mTOR) Ser2448, activity-regulated cytoskeleton-associated protein (Arc/Arg 3.1) and brain-derived neurotrophic factor (BDNF) in response to anthocyanin treatment, whilst α-E-catenin, c-Jun N-terminal kinase (JNK1) and p38 protein levels decreased. Together, these findings suggest that purified anthocyanin consumption enhances spatial learning and motor coordination in aged animals and can be attributed to the modulation of key synaptic proteins, which support integrity and maintenance of synaptic function.

Ferulic Acid Derivatives and Avenanthramides Modulate Endothelial Function through Maintenance of Nitric Oxide Balance in HUVEC Cells.

Wholegrain oats contain a variety of phenolic compounds thought to help maintain healthy vascular function, through the maintenance of local levels of the vasodilator nitric oxide (NO). Thus, the full molecular mechanisms involved are not yet clear. With this work we aim to understand the possible cellular mechanisms by which avenanthramides and ferulic acid derivatives, present in oats, may help maintain a healthy vascular function through the modulation of the NO pathway. Primary Human Umbilical Vein Endothelial Cells (HUVEC) were exposed to ferulic acid, isoferulic acid, hydroferulic acid, ferulic acid 4-O-glucuronide, isoferulic acid 3-O-sulfate, dihydroferulic acid 4-O-glucuronide, avenanthramide A, avenanthramide B and avenanthramide C (1 µM) or vehicle (methanol) for 24 h. Apocynin and Nω-Nitro-L-arginine (L-NNA) were additionally included as controls. NO and cyclic GMP (cGMP) levels, superoxide production and the activation of the Akt1/eNOS pathway were assessed. The statistical analysis was performed using one-way ANOVA followed by a Tukey post-hoc t-test. Apocynin and all phenolic compounds increased NO levels in HUVEC cells (increased DAF2-DA fluorescence and cGMP), and significantly reduced superoxide levels. Protein expression results highlighted an increase in the Akt1 activation state, and increased eNOS expression. Overall, our results indicated that the glucuronide metabolites do not enhance NO production through the Akt1/eNOS pathway, thus all compounds tested are able to reduce NO degradation through reduced superoxide formation.

Increased bioavailability of phenolic acids and enhanced vascular function following intake of feruloyl esterase-processed high fibre bread: A randomized, controlled, single blind, crossover human intervention trial.

BACKGROUND & AIMS: Clinical trial data have indicated an association between wholegrain consumption and a reduction in surrogate markers of cardiovascular disease. Phenolics present in wholegrain bound to arabinoxylan fibre may contribute these effects, particularly when released enzymatically from the fiber prior to ingestion. The aim of the present study was therefore to determine whether the intake of high fibre bread containing higher free ferulic acid (FA) levels (enzymatically released during processing) enhances human endothelium-dependent vascular function. METHODS: A randomized, single masked, controlled, crossover, human intervention study was conducted on 19 healthy men. Individuals consumed either a high fibre flatbread with enzymatically released free FA (14.22 mg), an equivalent standard high fibre bread (2.34 mg), or a white bread control (0.48 mg) and markers of vascular function and plasma phenolic acid concentrations were measured at baseline, 2, 5 and 7 h post consumption. RESULTS: Significantly increased brachial arterial dilation was observed following consumption of the high free FA ('enzyme-treated') high fibre bread verses both a white bread (2 h: p < 0.05; 5 h: p < 0.01) and a standard high fibre bread (5 h: p < 0.05). Concurrently, significant increases in plasma FA levels were observed, at 2 h (p < 0.01) after consumption of the enzyme-treated bread, relative to control treatments. Blood pressure, heart rate, DVP-SI and DVP-RI were not significantly altered following intake of any of the breads (p > 0.05). CONCLUSION: Dietary intake of bread, processed enzymatically to release FA from arabinoxylan fiber during production increases the bioavailability of FA, and induces acute endothelium-dependent vasodilation. CLINICAL TRIAL REGISTRY: NO: NCT03946293. WEBSITE: www.clinicaltrials.gov.

Nutrition and the ageing brain: Moving towards clinical applications.

The global increases in life expectancy and population have resulted in a growing ageing population and with it a growing number of people living with age-related neurodegenerative conditions and dementia, shifting focus towards methods of prevention, with lifestyle approaches such as nutrition representing a promising avenue for further development. This overview summarises the main themes discussed during the 3rd Symposium on "Nutrition for the Ageing Brain: Moving Towards Clinical Applications" held in Madrid in August 2018, enlarged with the current state of knowledge on how nutrition influences healthy ageing and gives recommendations regarding how the critical field of nutrition and neurodegeneration research should move forward into the future. Specific nutrients are discussed as well as the impact of multi-nutrient and whole diet approaches, showing particular promise to combatting the growing burden of age-related cognitive decline. The emergence of new avenues for exploring the role of diet in healthy ageing, such as the impact of the gut microbiome and development of new techniques (imaging measures of brain metabolism, metabolomics, biomarkers) are enabling researchers to approach finding answers to these questions. But the translation of these findings into clinical and public health contexts remains an obstacle due to significant shortcomings in nutrition research or pressure on the scientific community to communicate recommendations to the general public in a convincing and accessible way. Some promising programs exist but further investigation to improve our understanding of the mechanisms by which nutrition can improve brain health across the human lifespan is still required.

Composition and content of phenolic acids and avenanthramides in commercial oat products: Are oats an important polyphenol source for consumers?

Oats contain a range of phenolic acids and avenanthramides which may have health benefits. Analysis of 22 commercial oat products (oat bran concentrate, oat bran, flaked oats, rolled oats and oatcakes) using HPLC-DAD detected eleven bound and thirteen free + conjugated phenolic acids and avenanthramides. The oat products (excluding concentrate) provided between 15.79 and 25.05 mg total phenolic acids (9.9-19.33 mg bound, 4.96-5.72 mg free + conjugated) and between 1.1 and 2 mg of avenanthramides in a 40 g portion while an 11 g portion of oat concentrate provided 16.7 mg of total phenolic acids (15.17 mg bound, 1.53 mg free + conjugated) and 1.2 mg of avenanthramides. The compositions and concentrations of the components in the different products were broadly similar, with the major component being ferulic acid (58-78.1%). The results show that commercial oat products are a source of phenolic acids and avenanthramides for consumers.

Synthetic, non-intoxicating 8,9-dihydrocannabidiol for the mitigation of seizures.

There can be a fine line between therapeutic intervention and substance abuse, and this point is clearly exemplified in herbal cannabis and its products. Therapies involving cannabis have been the treatment of last resort for some cases of refractory epilepsy, and this has been among the strongest medical justifications for legalization of marijuana. In order to circumvent the narcotic effects of Δ9-tetrahydrocannabinol (THC), many studies have concentrated on its less intoxicating isomer cannabidiol (CBD). However, CBD, like all natural cannabinoids, is a controlled substance in most countries, and its conversion into THC can be easily performed using common chemicals. We describe here the anticonvulsant properties of 8,9-dihydrocannibidiol (H2CBD), a fully synthetic analogue of CBD that is prepared from inexpensive, non-cannabis derived precursors. H2CBD was found to have effectiveness comparable to CBD both for decreasing the number and reducing the severity of pentylenetetrazole-induced seizures in rats. Finally, H2CBD cannot be converted by any reasonable synthetic route into THC, and thus has the potential to act as a safe, noncontroversial drug for seizure mitigation.

Acute Effects of Hibiscus Sabdariffa Calyces on Postprandial Blood Pressure, Vascular Function, Blood Lipids, Biomarkers of Insulin Resistance and Inflammation in Humans.

BACKGROUND/OBJECTIVES: The acute impact of Hibiscus sabdariffa calyces (HSC) extract on postprandial vascular function and other cardiometabolic risk factors have not been studied previously. This study investigated the acute impact of HSC extract consumption on blood pressure (BP), vascular function and other cardiometabolic risk markers. SUBJECTS/METHODS: Twenty-five men with 1% to 10% cardiovascular disease (CVD) risk (determined by QRISK®2) were randomised to consume either 250 mL of the aqueous extract of HSC or water with breakfast in a randomised, controlled, single-blinded, 2-meal cross-over study (ClinicalTrials.gov, NTC02165553) with a two weeks washout period between study days. BP was measured at baseline and hourly for 4 h. Flow mediated dilatation (FMD) of the branchial artery was measured at baseline, 2 and 4 h post intervention drink consumption. RESULTS: Acute consumption of aqueous extract of HSC caused a significant increase in % FMD (p < 0.001), a non-significant decrease in systolic BP (SBP) and diastolic BP (DBP); non-significant increase in urinary and plasma nitric oxide (NOx) and reduced response of serum glucose, plasma insulin, serum triacylglycerol and C-reactive protein (CRP) levels; significant (p = 0.026) improvement in the area under systemic antioxidant response curve (0 to 2 h); no significant changes in arterial stiffness following the acute consumption of the extract of HSC. Gallic acid, 4-O-methylgallic acid, 3-O-methylgallic acid and hippuric acid reached a maximum plasma concentration at 1 to 2 h post consumption of the extract of HSC. CONCLUSION: The extract of HSC improved postprandial vascular function and may be a useful dietary strategy to reduce endothelial dysfunction and CVD risk, although this requires confirmation.

Oat bran, but not its isolated bioactive ß-glucans or polyphenols, have a bifidogenic effect in an in vitro fermentation model of the gut microbiota.

Wholegrain oats are known to modulate the human gut microbiota and have prebiotic properties (increase the growth of some health-promoting bacterial genera within the colon). Research to date mainly attributes these effects to the fibre content; however, oat is also a rich dietary source of polyphenols, which may contribute to the positive modulation of gut microbiota. In vitro anaerobic batch-culture experiments were performed over 24 h to evaluate the impact of two different doses (1 and 3 % (w/v)) of oat bran, matched concentrations of ß-glucan extract or polyphenol mix, on the human faecal microbiota composition using 16S RNA gene sequencing and SCFA analysis. Supplementation with oats increased the abundance of Proteobacteria (P <0·01) at 10 h, Bacteroidetes (P <0·05) at 24 h and concentrations of acetic and propionic acid increased at 10 and 24 h compared with the NC. Fermentation of the 1 % (w/v) oat bran resulted in significant increase in SCFA production at 24 h (86 (sd 27) v. 28 (sd 5) mm; P <0·05) and a bifidogenic effect, increasing the relative abundance of Bifidobacterium unassigned at 10 h and Bifidobacterium adolescentis (P <0·05) at 10 and 24 h compared with NC. Considering the ß-glucan treatment induced an increase in the phylum Bacteroidetes at 24 h, it explains the Bacteriodetes effects of oats as a food matrix. The polyphenol mix induced an increase in Enterobacteriaceae family at 24 h. In conclusion, in this study, we found that oats increased bifidobacteria, acetic acid and propionic acid, and this is mediated by the synergy of all oat compounds within the complex food matrix, rather than its main bioactive ß-glucan or polyphenols. Thus, oats as a whole food led to the greatest impact on the microbiota.

The Effects of Flavonoids on Cardiovascular Health: A Review of Human Intervention Trials and Implications for Cerebrovascular Function.

Research has suggested a number of beneficial effects arising from the consumption of dietary flavonoids, found in foods such as cocoa, apples, tea, citrus fruits and berries on cardiovascular risk factors such as high blood pressure and endothelial dysfunction. These effects are thought to have a significant impact upon both vascular and cerebrovascular health, ultimately with the potential to prevent cardiovascular and potentially neurodegenerative disease with a vascular component, for example vascular dementia. This review explores the current evidence for the effects of flavonoid supplementation on human endothelial function and both peripheral and cerebral blood flow (CBF). Evidence presented includes their potential to reduce blood pressure in hypertensive individuals, as well as increasing peripheral blood perfusion and promoting CBF in both healthy and at-risk populations. However, there is great variation in the literature due to the heterogeneous nature of the randomised controlled trials conducted. As such, there is a clear need for further research and understanding within this area in order to maximise potential health benefits.

Gut microbiota modulation accounts for the neuroprotective properties of anthocyanins.

High-fat (HF) diets are thought to disrupt the profile of the gut microbiota in a manner that may contribute to the neuroinflammation and neurobehavioral changes observed in obesity. Accordingly, we hypothesize that by preventing HF-diet induced dysbiosis it is possible to prevent neuroinflammation and the consequent neurological disorders. Anthocyanins are flavonoids found in berries that exhibit anti-neuroinflammatory properties in the context of obesity. Here, we demonstrate that the blackberry anthocyanin-rich extract (BE) can modulate gut microbiota composition and counteract some of the features of HF-diet induced dysbiosis. In addition, we show that the modifications in gut microbial environment are partially linked with the anti-neuroinflammatory properties of BE. Through fecal metabolome analysis, we unravel the mechanism by which BE participates in the bilateral communication between the gut and the brain. BE alters host tryptophan metabolism, increasing the production of the neuroprotective metabolite kynurenic acid. These findings strongly suggest that dietary manipulation of the gut microbiota with anthocyanins can attenuate the neurologic complications of obesity, thus expanding the classification of psychobiotics to anthocyanins.

Inhibition of PP2A by hesperetin may contribute to Akt and ERK1/2 activation status in cortical neurons.

Flavonoids and their metabolites are well reported to modulate the activation/phosphorylation of various cellular kinases, such as ERK1/2 and JNK, although the mechanism by which they do so is unclear. In this study, we investigated the impact of flavanones on the activation of PI3K/Akt and ERK1/2 and determine whether this is mediated, in part, by the inhibition of phosphatases. Primary cortical neurons were exposed to physiological concentrations of hesperetin and the phosphorylation status of the kinases PI3K/Akt and ERK1/2 and the phosphatases PP2A and PTEN were assessed by immunoblotting after 30 min. Exposure to 100-300 nM hesperetin led to significant increases in the phosphorylation of ERK1/2 and Akt and significant decreases in PP2A levels and enzyme activity. Using in silico docking, hesperetin was found to fit into the active site of PP2A interacting within the hydrophobic cage of the catalytic unit. These data suggest a potential mechanism by which flavanones may lead to increased activation of ERK1/2 and Akt, commonly observed in cell models. Their interaction with and inhibition of cellular phosphatases counteract normal physiological regulation of signaling pathway activation thus facilitating and/or maintaining the activation status of ERK1/2 and Akt, important regulators of brain functions.

Recommending flavanols and procyanidins for cardiovascular health: Revisited.

The last 8 years have seen significant developments in our understanding of dietary flavanols and procyanidins in the context of human health and nutrition. During the same time, recognition of the importance of nutrition in primary disease prevention and health maintenance has increased. In addition, the concept of dietary bioactives (food constituents that although not essential to human life and procreation, may nevertheless play an important role in disease risk reduction, primary disease prevention, and healthy aging) has been created and developed. Applying assessment criteria specific to health maintenance and primary disease prevention, we aimed at broadly evaluating and discussing currently available data on flavanols and procyanidins, with an eye towards potentially advancing the future development of dietary guidelines and public health recommendations. Novel insights and advancements as well as current gaps and shortcomings in our understanding are identified and discussed. While centered on flavanols and procyanidins, the outcomes of this review may also have broader relevance for the further development of the concept of bioactives, and any future framework for the assessment of their role in human health and nutrition.

Effects of pelargonidin-3-O-glucoside and its metabolites on lipopolysaccharide-stimulated cytokine production by THP-1 monocytes and macrophages.

Epidemiological evidence suggests cardioprotective effects of anthocyanin consumption. This study examined the predominant strawberry anthocyanin, pelargonidin-3-O-glucoside (Pg-3-glc), and three of its plasma metabolites (protocatechuic acid [PCA], 4-hydroxybenzoic acid, and phloroglucinaldehyde [PGA]) for effects on the production of selected cytokines by lipopolysaccharide-stimulated THP-1 monocytes and macrophages. Concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, IL-8 and IL-10 were determined using a cytometric bead array kit. PCA at 0.31, 1.25 and 20 µM and PGA at 5 and 20 µM decreased the concentration of IL-6 in the monocyte cultures, but there were no effects on TNF-α, IL-1ß, IL-8 and IL-10 and there were no effects of the other compounds. In the macrophage cultures, PGA at 20 µM decreased the concentrations of IL-6 and IL-10, but there was no effect on TNF-α, IL-1ß and IL-8 and there were no effects of the other compounds. In conclusion, while the effects of PGA were only observed at the higher, supraphysiological concentration and are thus considered of limited physiological relevance overall, the anti-inflammatory properties of PCA were observed at both the lower, physiologically relevant, and the higher concentrations; however, effects were modest and limited to IL-6 and monocytes. These preliminary data suggest potential for physiologically attainable PCA concentrations to modulate IL-6 production by monocytes.

Poor cognitive ageing: Vulnerabilities, mechanisms and the impact of nutritional interventions.

BACKGROUND: Ageing is a highly complex process marked by a temporal cascade of events, which promote alterations in the normal functioning of an individual organism. The triggers of normal brain ageing are not well understood, even less so the factors which initiate and steer the neuronal degeneration, which underpin disorders such as dementia. A wealth of data on how nutrients and diets may support cognitive function and preserve brain health are available, yet the molecular mechanisms underlying their biological action in both normal ageing, age-related cognitive decline, and in the development of neurodegenerative disorders have not been clearly elucidated. OBJECTIVES: This review aims to summarise the current state of knowledge of vulnerabilities that predispose towards dysfunctional brain ageing, highlight potential protective mechanisms, and discuss dietary interventions that may be used as therapies. A special focus of this paper is on the impact of nutrition on neuroprotection and the underlying molecular mechanisms, and this focus reflects the discussions held during the 2nd workshop 'Nutrition for the Ageing Brain: Functional Aspects and Mechanisms' in Copenhagen in June 2016. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe). CONCLUSION: Coupling studies of cognitive ageing with studies investigating the effect of nutrition and dietary interventions as strategies targeting specific mechanisms, such as neurogenesis, protein clearance, inflammation, and non-coding and microRNAs is of high value. Future research on the impact of nutrition on cognitive ageing will need to adopt a longitudinal approach and multimodal nutritional interventions will likely need to be imposed in early-life to observe significant impact in older age.

Excretion of Avenanthramides, Phenolic Acids and their Major Metabolites Following Intake of Oat Bran.

SCOPE: Wholegrain has been associated with reduced chronic disease mortality, with oat intake particularly notable for lowering blood cholesterol and glycemia. To better understand the complex nutrient profile of oats, we studied urinary excretion of phenolic acids and avenanthramides after ingestion of oat bran in humans. METHODS AND RESULTS: After a 2-d (poly)phenol-low diet, seven healthy men provided urine 12 h before and 48 h after consuming 60 g oat bran (7.8 µmol avenanthramides, 139.2 µmol phenolic acids) or a phenolic-low (traces of phenolics) control in a crossover design. Analysis by ultra-high performance liquid chromatography (UPLC)-MS/MS showed that oat bran intake resulted in an elevation in urinary excretion of 30 phenolics relative to the control, suggesting that they are oat bran-derived. Mean excretion levels were elevated between 0-2 and 4-8 h, following oat bran intake, and amounted to a total of 33.7 ± 7.3 µmol total excretion (mean recovery: 22.9 ± 5.0%), relative to control. The predominant metabolites included: vanillic acid, 4- and 3-hydroxyhippuric acids, and sulfate-conjugates of benzoic and ferulic acids, which accounted collectively for two thirds of total excretion. CONCLUSION: Oat bran phenolics follow a relatively rapid urinary excretion, with 30 metabolites excreted within 8 h of intake. These levels of excretion suggest that bound phenolics are, in part, rapidly released by the microbiota.

Olive Oil Phenolics Prevent Oxysterol-Induced Proinflammatory Cytokine Secretion and Reactive Oxygen Species Production in Human Peripheral Blood Mononuclear Cells, Through Modulation of p38 and JNK Pathways.

SCOPE: The aim of the present study was to investigate the ability of extra virgin olive oil (EVOO) polyphenols to counteract the proinflammatory effects induced by dietary and endogenous oxysterols in ex vivo immune cells. METHODS AND RESULTS: Peripheral blood mononuclear cells (PBMCs), separated from the whole blood of healthy donors, were utilized and were stimulated with an oxysterols mixture, in the presence of physiologically relevant concentrations of the EVOO polyphenols, hydroxytyrosol, tyrosol, and homovanillic alcohol. Oxysterols significantly increased the production of proinflammatory cytokines, interleukin-1ß, regulated on activation, normal T-cell expressed and secreted and macrophage migration inhibitory factor in ex vivo cultured PBMCs. Increased levels of reactive oxygen species (ROS) were also detected along with increased phosphorylation of the p38 and JNK. All phenolic compounds significantly reduced cytokine secretion induced by the oxysterols and inhibited ROS production and mitogen activated protein kinase phosphorylation. CONCLUSIONS: These results suggest that extra virgin olive oil polyphenols modulate the immune response induced by dietary and endogenous cholesterol oxidation products in human immune cells and may hold benefit in controlling chronic immune and/or inflammatory processes.

Effect of simulated gastrointestinal digestion and fermentation on polyphenolic content and bioactivity of brown seaweed phlorotannin-rich extracts.

SCOPE: Unlike other classes of polyphenols, there is a lack of knowledge regarding brown seaweed phlorotannins and their bioactivity. We investigated the impact of in vitro gastrointestinal digestion and colonic fermentation on the bioactivity of a seaweed phlorotannin extract from Ascophyllum nodosum and its high molecular weight (HMW) and low molecular weight (LMW) fractions. METHODS AND RESULTS: The highest phlorotannin and total polyphenol (TP) concentration was observed in the HMW fraction. Antioxidant capacity broadly followed phlorotannin and TP levels, with HMW having the highest activity. Both gastrointestinal digestion (GID) and colonic fermentation (CF) significantly affected phlorotannin and TP levels, and antioxidant capacity of the extract and fractions. Despite this, in HT-29 cells, all GID extracts significantly inhibit cell growth, whereas CF extracts effectively counteracted H2 O2 induced DNA damage. CONCLUSION: Although phlorotannins, TP levels and antioxidant power of the extracts were strongly reduced after in vitro digestion and fermentation, their anti-genotoxic activity and cell growth inhibitory effect in colon HT-29 cells was maintained and enhanced. HMW was the most effective fraction, indicating that the high molecular weight phlorotannins potentially exert a stronger beneficial effect in the colon.