Inhibitory effect of extracts from edible parts of nuts on α-amylase activity: a systematic review.

Elevated blood glucose concentration is a risk factor for developing metabolic dysfunction and insulin resistance, leading to type 2 diabetes and cardiovascular diseases. Nuts have the potential to inhibit α-amylase activity, and so lower postprandial glucose, due to their content of polyphenols and other bioactive compounds. We conducted a systematic literature review to assess the ability of extracts from commonly consumed edible parts of nuts to inhibit α-amylase. Among the 31 included papers, only four utilised human α-amylases. These papers indicated that polyphenol-rich chestnut skin extracts exhibited strong inhibition of both human salivary and pancreatic α-amylases, and that a polyphenol-rich almond skin extract was a potent inhibitor of human salivary α-amylase. The majority of the reviewed studies utilised porcine pancreatic α-amylase, which has ∼86% sequence homology with the corresponding human enzyme but with some key amino acid variations located within the active site. Polyphenol-rich extracts from chestnut, almond, kola nut, pecan and walnut, and peptides isolated from cashew, inhibited porcine pancreatic α-amylase. Some studies used α-amylases sourced from fungi or bacteria, outcomes from which are entirely irrelevant to human health, as they have no sequence homology with the human enzyme. Given the limited research involving human α-amylases, and the differences in inhibition compared to porcine enzymes and especially enzymes from microorganisms, it is recommended that future in vitro experiments place greater emphasis on utilising enzymes sourced from humans to facilitate a reliable prediction of effects in intervention studies.

Effects of (Poly)phenols on Circadian Clock Gene-Mediated Metabolic Homeostasis in Cultured Mammalian Cells: A Scoping Review.

Circadian clocks regulate metabolic homeostasis. Disruption to our circadian clocks, by lifestyle behaviors such as timing of eating and sleeping, has been linked to increased rates of metabolic disorders. There is now considerable evidence that selected dietary (poly)phenols, including flavonoids, phenolic acids and tannins, may modulate metabolic and circadian processes. This review evaluates the effects of (poly)phenols on circadian clock genes and linked metabolic homeostasis in vitro, and potential mechanisms of action, by critically evaluating the literature on mammalian cells. A systematic search was conducted to ensure full coverage of the literature and identified 43 relevant studies addressing the effects of (poly)phenols on cellular circadian processes. Nobiletin and tangeretin, found in citrus, (-)-epigallocatechin-3-gallate from green tea, urolithin A, a gut microbial metabolite from ellagitannins in fruit, curcumin, bavachalcone, cinnamic acid, and resveratrol at low micromolar concentrations all affect circadian molecular processes in multiple types of synchronized cells. Nobiletin emerges as a putative retinoic acid-related orphan receptor (RORα/γ) agonist, leading to induction of the circadian regulator brain and muscle ARNT-like 1 (BMAL1), and increased period circadian regulator 2 (PER2) amplitude and period. These effects are clear despite substantial variations in the protocols employed, and this review suggests a methodological framework to help future study design in this emerging area of research.

Flavonoids and phenolic acids from sugarcane: Distribution in the plant, changes during processing, and potential benefits to industry and health.

Sugarcane (Saccharum sp.) plants are grown in warmer climates throughout the world and processed to produce sugar as well as other useful byproducts such as molasses and bagasse. Sugarcane is rich in (poly)phenols, but there has been no attempt to critically evaluate the published information based on the use of suitable methodologies. The objective of this review is to evaluate the quantitative and qualitative (poly)phenolic profiles of individual parts of the sugarcane plant and its multiple industrial products, which will help develop new processes and uses for sugarcane (poly)phenols. The quantitative analysis involves the examination of extraction, concentration, and analytical techniques used in each study for each plant part and product. The qualitative analysis indicates the identification of various (poly)phenols throughout the sugarcane processing chain, using only compounds elucidated through robust analytical methodologies such as mass spectrometry or nuclear magnetic resonance. In conclusion, sugarcane (poly)phenols are predominantly flavonoids and phenolic acids. The main flavonoids, derivatives of apigenin, luteolin, and tricin, with a substantial proportion of C-glycosides, are consistently found across all phases of sugarcane processing. The principal phenolic acids reported throughout the process include chlorogenic acids, as well as ferulic and caffeic acids mostly observed after hydrolysis. The derivation of precise quantitative information across publications is impeded by inconsistencies in analytical methodologies. The presence of multiple (poly)phenols with potential benefits for industrial applications and for health suggests sugarcane could be a useful provider of valuable compounds for future use in research and industrial processes.

A critical examination of human data for the biological activity of quercetin and its phase-2 conjugates.

This critical review examines evidence for beneficial effects of quercetin phase-2 conjugates from clinical intervention studies, volunteer feeding trials, and in vitro work. Plasma concentrations of quercetin-3-O-glucuronide (Q3G) and 3'-methylquercetin-3-O-glucuronide (3'MQ3G) after supplementation may produce beneficial effects in macrophages and endothelial cells, respectively, especially if endogenous deglucuronidation occurs, and lower blood uric acid concentration via quercetin-3'-O-sulfate (Q3'S). Unsupplemented diets produce much lower concentrations (<50 nmol/l) rarely investigated in vitro. At 10 nmol/l, Q3'S and Q3G stimulate or suppress, respectively, angiogenesis in endothelial cells. Statistically significant effects have been reported at 100 nmol/l in breast cancer cells (Q3G), primary neuron cultures (Q3G), lymphocytes (Q3G and3'MQ3G) and HUVECs (QG/QS mixture), but it is unclear whether these translate to a health benefit in vivo. More sensitive and more precise methods to measure clinically significant endpoints are required before a conclusion can be drawn regarding effects at normal dietary concentrations. Future requirements include better understanding of inter-individual and temporal variation in plasma quercetin phase-2 conjugates, their mechanisms of action including deglucuronidation and desulfation both in vitro and in vivo, tissue accumulation and washout, as well as potential for synergy or antagonism with other quercetin metabolites and metabolites of other dietary phytochemicals.

Short-term effect of a carbon fiber custom dynamic orthosis and integrated rehabilitation on self-reported physical function, pain, speed, and agility in civilians.

BACKGROUND: Ankle-foot orthoses (AFOs) are widely used to restore mobility and reduce pain in individuals with lower extremity pain and disability. The use of a carbon fiber custom dynamic orthosis (CDO) with integrated physical training and psychosocial intervention has been shown to improve outcomes in a military setting, but civilian data are limited. OBJECTIVES: To use existing clinical data to evaluate the initial effectiveness of an integrated CDO and rehabilitative program and identify baseline characteristics that impact patient response to the intervention. STUDY DESIGN: Retrospective cohort. METHODS: Records of 131 adult patients who received a CDO and device specific training were reviewed. Patient-reported measures of pain and lower extremity function and physical measurements of walking and agility were extracted at baseline and on training completion. RESULTS: A majority of patients reported improved or greatly improved physical function (92%), maximum pain (69%), and typical pain (55%) and experienced improved or greatly improved walking speed (92%) and agility (52%) irrespective of age and sex. Regression models for examining short-term improvement in pain and physical function accounted for 52% (p < 0.001) and 26% (p < 0.001) of the outcome variance, respectively. Improvement in typical pain was influenced by baseline typical and maximum pain, and functional improvement was influenced by sex and baseline physical function. CONCLUSIONS: Most patients (92.4%) reported a positive initial outcome after intervention as measured using patient-reported and objective measures.

Predictors of long-term pain and function in individuals who received a custom dynamic orthosis and device-centric care pathway.

INTRODUCTION: Carbon fiber custom dynamic orthoses (CDOs) have been shown to effectively reduce pain and improve function in military service members with lower-limb impairment, but data are limited for civilians. OBJECTIVES: To evaluate the long-term outcomes of individuals who completed a CDO-centric care pathway in a civilian clinic by comparing baseline pain, mobility, and function with outcomes at long-term follow-up. To identify baseline characteristics and postintervention outcomes predictive of outcomes at long-term follow-up. METHODS: Records of 131 adult patients who received a CDO and CDO-centric training were reviewed. Patient-reported measures of pain and physical function and timed assessment of walking and agility collected during routine clinical care were extracted. These patients were contacted on average 4 (±1) years postintervention to complete a survey including measures of pain and physical function. RESULTS: The 63 participants who responded reported improved or greatly improved function, maximum pain, and typical pain on average, irrespective of age or sex (P < 0.001). Change in function from baseline to long-term follow-up was predicted by short-term change in function (35.1% of the variance; P < 0.001). Change in pain from baseline to long-term follow-up was predicted by baseline typical pain and change in four square step test time (63% of variance; P < 0.001). CONCLUSIONS: Most survey respondents reported positive outcomes. Long-term pain reduction and improved function were predicted by baseline status and by short-term changes associated with receiving a CDO and completing an intensive training program.

Systematic Review and Quantitative Data Synthesis of Peripheral Blood Mononuclear Cell Transcriptomics Reveals Consensus Gene Expression Changes in Response to a High Fat Meal.

SCOPE: Metabolic flexibility is essential for a healthy response to a high fat meal, and is assessed by measuring postprandial changes in blood markers including peripheral blood mononuclear cells (PBMCs; lymphocytes and monocytes). However, there is no clear consensus on postprandial gene expression and protein changes in these cells. METHOD AND RESULTS: The study systematically reviews the literature reporting transcriptional and proteomic changes in PBMCs after consumption of a high fat meal. After re-analysis of the raw data to ensure equivalence between studies, ≈85 genes are significantly changed (defined as in the same direction in ≥3 studies) with about half involved in four processes: inflammation/oxidative stress, GTP metabolism, apoptosis, and lipid localization/transport. For meals consisting predominantly of unsaturated fatty acids (UFA), notable additional processes are phosphorylation and glucocorticoid response. For saturated fatty acids (SFA), genes related to migration/angiogenesis and platelet aggregation are also changed. CONCLUSION: Despite differences in study design, common gene changes are identified in PBMCs following a high fat meal. These common genes and processes will facilitate definition of the postprandial transcriptome as part of the overall postcibalome, linking all molecules and processes that change in the blood after a meal.

Plasma measurements of the dual sugar test reveal carbohydrate immediately alleviates intestinal permeability caused by exertional heat stress.

The aim of this set of randomised cross-over studies was to determine the impact of progressive heat exposure and carbohydrate or protein feeding during exertional stress on small intestine permeability using a dual sugar test. In our previous work, and typically in the field, recovery of lactulose and l-rhamnose is measured cumulatively in urine. This follow-up study exploits our novel high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) protocol to accurately quantify the sugars in plasma. Endurance-trained participants completed experimental trial A (ET-A; n = 8), consisting of 2 h running at 60% V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ in temperate, warm and hot ambient conditions, and/or experimental trial B (ET-B; n = 9), consisting of 2 h running at 60% V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ in the heat while consuming water, carbohydrate or protein. Blood samples were collected and plasma lactulose (L) and l-rhamnose (R) appearance, after dual sugar solution ingestion at 90 min of exercise, was quantified by HPAEC-PAD to measure plasma L/R and reveal new information about intestinal permeability immediately post-exercise and during recovery. In ET-A, plasma L/R increased immediately post-exercise in hot compared with temperate and warm conditions, while, in ET-B, carbohydrate alleviated this, and this information was otherwise missed when measuring urine L/R. Consuming carbohydrate or protein before and during exercise attenuated small intestine permeability throughout recovery from exertional heat stress. We recommend using the dual sugar test with quantification of plasma sugars by HPAEC-PAD at intervals to maximise intestinal permeability data collection in exercise gastroenterology research, as this gives additional information compared to urinary measurements. KEY POINTS: Intestinal permeability is typically assessed using a dual sugar test, by administering a drink containing non-metabolisable sugars (e.g. lactulose (L) and l-rhamnose (R)) that can enter the circulation by paracellular translocation when the epithelium is compromised, and are subsequently measured in urine. We demonstrate that our recently developed ion chromatography protocol can be used to accurately quantify the L/R ratio in plasma, and that measuring L/R in plasma collected at intervals during the post-exercise recovery period reveals novel acute response information compared to measuring 5-h cumulative urine L/R. We confirm that exercising in hot ambient conditions increases intestinal epithelial permeability immediately after exercise, while consuming carbohydrate or protein immediately before and during exercise attenuates this. We recommend using our dual sugar absorption test protocol to maximise intestinal epithelial permeability data collection in exercise gastroenterology research and beyond.

Exploring the anti-inflammatory activity of sulforaphane.

Dysregulation of innate immune responses can result in chronic inflammatory conditions. Glucocorticoids, the current frontline therapy, are effective immunosuppressive drugs but come with a trade-off of cumulative and serious side effects. Therefore, alternative drug options with improved safety profiles are urgently needed. Sulforaphane, a phytochemical derived from plants of the brassica family, is a potent inducer of phase II detoxification enzymes via nuclear factor-erythroid factor 2-related factor 2 (NRF2) signaling. Moreover, a growing body of evidence suggests additional diverse anti-inflammatory properties of sulforaphane through interactions with mediators of key signaling pathways and inflammatory cytokines. Multiple studies support a role for sulforaphane as a negative regulator of nuclear factor kappa-light chain enhancer of activated B cells (NF-κB) activation and subsequent cytokine release, inflammasome activation and direct regulation of the activity of macrophage migration inhibitory factor. Significantly, studies have also highlighted potential steroid-sparing activity for sulforaphane, suggesting that it may have potential as an adjunctive therapy for some inflammatory conditions. This review discusses published research on sulforaphane, including proposed mechanisms of action, and poses questions for future studies that might help progress our understanding of the potential clinical applications of this intriguing molecule.

A systematic review of the inhibitory effect of extracts from edible parts of nuts on α-glucosidase activity.

An elevated postprandial glycaemic response is a risk factor for developing type 2 diabetes mellitus (T2DM). Inhibition of digestive enzymes, including membrane-bound brush-border α-glucosidases, leads to slowed carbohydrate digestion and absorption, and reduced postprandial glycaemia. Nuts are eaten widely around the world, and have the potential to inhibit α-glucosidases through their content of polyphenols and other bioactive compounds. We set out to conduct a systematic literature review exploring the inhibitory effect of extracts from edible parts of various nuts on α-glucosidase activity in vitro to ensure, as far as possible, that no papers were missed. After an initial screening, 38 studies were reviewed in full, of which 15 were suitable for the present systematic review. Notably, no studies were found which tested the inhibitory potential of nut extracts against human α-glucosidases. Two studies showed that extracts from almonds and hazelnuts inhibited rat α-glucosidase activity, but the remaining papers reported data on the yeast α-glucosidase enzyme. Where yeast and rat enzymes can be compared, it is clear that nut extracts inhibit yeast α-glucosidase more strongly than mammalian α-glucosidase, which may lead to over-estimation when predicting effects in vivo when using data from the yeast enzyme. In contrast, acarbose is a stronger inhibitor of mammalian α-glucosidase compared to the yeast enzyme. Thus, although the present review indicates that extracts from nuts inhibit yeast α-glucosidase, this cannot be extrapolated to humans in vivo. There is some evidence that extracts from almonds and hazelnuts inhibit rat α-glucosidase, but no information on human enzyme sources. Since most work has been published on the yeast enzyme, future work in vitro must utilise mammalian, and preferably human, α-glucosidases in order to be relevant to human health and disease. This systematic review was registered at INPLASY as INPLASY202280061.

Demonstrating a link between diet, gut microbiota and brain: 14C radioactivity identified in the brain following gut microbial fermentation of 14C-radiolabeled tyrosine in a pig model.

Background: There is a need to better understand the relationship between the diet, the gut microbiota and mental health. Metabolites produced when the human gut microbiota metabolize amino acids may enter the bloodstream and have systemic effects. We hypothesize that fermentation of amino acids by a resistant protein-primed gut microbiota could yield potentially toxic metabolites and disturb the availability of neurotransmitter precursors to the brain. However, these mechanisms are challenging to investigate via typical in vitro and clinical methods. Methods: We developed a novel workflow using 14C radiolabeling to investigate complex nutrient-disease relationships. The first three steps of the workflow are reported here. α-Linolenic acid (ALA) was used as a model nutrient to confirm the efficacy of the workflow, and tyrosine (Tyr) was the test nutrient. 14C-Tyr was administered to male weanling pigs fed a high resistant protein diet, which primed the gut microbiota for fermenting protein. The hypotheses were; (1) that expected biodistribution of 14C-ALA would be observed, and (2) that radioactivity from 14C-Tyr, representing Tyr and other amino acids released from resistant protein following gut microbial fermentation, would be bioavailable to the brain. Results: Radioactivity from the 14C-ALA was detected in tissues reflecting normal utilization of this essential fatty acid. Radioactivity from the 14C-Tyr was detected in the brain (0.15% of original dose). Conclusion: Metabolites of gut-fermented protein and specifically amino acid precursors to neurotransmitters such as tyrosine, are potentially able to affect brain function. By extension, resistant proteins in the diet reaching the gut microbiota, also have potential to release metabolites that can potentially affect brain function. The high specificity of detection of 14C radioactivity demonstrates that the proposed workflow can similarly be applied to understand other key diet and health paradigms.

Citrus polyphenols and risk of type 2 diabetes: Evidence from mechanistic studies.

Citrus fruits are a rich source of (poly)phenols, a group of dietary bioactive compounds that protect against developing type 2 diabetes. Our review critically evaluates how experimental in vitro and animal models have elucidated some of the underlying mechanisms on how citrus (poly)phenols affect the markers of type 2 diabetes. According to animal studies, the beneficial effects derived from consuming citrus compounds appear to be related to long-term effects, rather than acute. There are some notable effects from citrus (poly)phenol metabolites on post-absorptive processes, such as modulation of hepatic glucose metabolism and insulin sensitivity in target tissues, but with a more modest effect on digestion and sugar absorption within the gut. Experimental studies on cells and other systems in vitro have indicated some of the possible mechanisms involved, but ∼70% of the studies utilized unrealistically high concentrations and forms of the compounds, compromising physiological relevance. Future studies should discuss the relevance of concentration used in in vitro experiments, relative to the proposed site of action, and also examine the role of catabolites produced by the gut microbiota. Finally, it is important to examine the relationship between the gut microbiota and bioavailability on the action of citrus (poly)phenols.

Metabolism of phenolics in coffee and plant-based foods by canonical pathways: an assessment of the role of fatty acid ß-oxidation to generate biologically-active and -inactive intermediates.

ω-Phenyl-alkenoic acids are abundant in coffee, fruits, and vegetables. Along with ω-phenyl-alkanoic acids, they are produced from numerous dietary (poly)phenols and aromatic amino acids in vivo. This review addresses how phenyl-ring substitution and flux modulates their gut microbiota and endogenous ß-oxidation. 3',5'-Dihydroxy-derivatives (from alkyl-resorcinols, flavanols, proanthocyanidins), and 4'-hydroxy-phenolic acids (from tyrosine, p-coumaric acid, naringenin) are ß-oxidation substrates yielding benzoic acids. In contrast, 3',4',5'-tri-substituted-derivatives, 3',4'-dihydroxy-derivatives and 3'-methoxy-4'-hydroxy-derivatives (from coffee, tea, cereals, many fruits and vegetables) are poor ß-oxidation substrates with metabolism diverted via gut microbiota dehydroxylation, phenylvalerolactone formation and phase-2 conjugation, possibly a strategy to conserve limited pools of coenzyme A. 4'-Methoxy-derivatives (citrus fruits) or 3',4'-dimethoxy-derivatives (coffee) are susceptible to hepatic "reverse" hydrogenation suggesting incompatibility with enoyl-CoA-hydratase. Gut microbiota-produced 3'-hydroxy-4'-methoxy-derivatives (citrus fruits) and 3'-hydroxy-derivatives (numerous (poly)phenols) are excreted as the phenyl-hydracrylic acid ß-oxidation intermediate suggesting incompatibility with hydroxy-acyl-CoA dehydrogenase, albeit with considerable inter-individual variation. Further investigation is required to explain inter-individual variation, factors determining the amino acid to which C6-C3 and C6-C1 metabolites are conjugated, the precise role(s) of l-carnitine, whether glycine might be limiting, and whether phenolic acid-modulation of ß-oxidation explains how phenolic acids affect key metabolic conditions, such as fatty liver, carbohydrate metabolism and insulin resistance.

Review of factors affecting citrus polyphenol bioavailability and their importance in designing in vitro, animal, and intervention studies.

Evidence from in vitro, animal, and human studies links citrus fruit consumption with several health-promoting effects. However, many in vitro studies disregard bioavailability data, a key factor determining responses in humans. Citrus (poly)phenol metabolism and bioavailability follow specific pathways that vary widely among individuals and are affected by several intrinsic (age, sex, gut microbiota, metabolic state, genetic polymorphisms) and extrinsic (food matrix, co-consumed food, (poly)phenol solubility, dose, food processing, lifestyle) factors. The gut microbiota is crucial to both absorption of citrus (poly)phenols and the production of catabolites, and absorption of both takes place mostly in the colon. Citrus (poly)phenol absorption can reach up to 100% in some individuals when the sum of the gut microbiota products are taken into account. This review emphasizes the importance of understanding citrus (poly)phenol absorption, metabolism, and bioavailability using evidence primarily derived from human studies in designing in vitro, animal, and further human clinical studies.

Measuring key human carbohydrate digestive enzyme activities using high-performance anion-exchange chromatography with pulsed amperometric detection.

Carbohydrate digestion in the mammalian gastrointestinal tract is catalyzed by α-amylases and α-glucosidases to produce monosaccharides for absorption. Inhibition of these enzymes is the major activity of the drugs acarbose and miglitol, which are used to manage diabetes. Furthermore, delaying carbohydrate digestion via inhibition of α-amylases and α-glucosidases is an effective strategy to blunt blood glucose spikes, a major risk factor for developing metabolic diseases. Here, we present an in vitro protocol developed to accurately and specifically assess the activity of α-amylases and α-glucosidases, including sucrase, maltase and isomaltase. The assay is especially suitable for measuring inhibition by compounds, drugs and extracts, with minimal interference from impurities or endogenous components, because the substrates and digestive products in the enzyme activity assays are quantified directly by high-performance anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD). Multiple enzyme sources can be used, but here we present the protocol using commercially available human α-amylase to assess starch hydrolysis with maltoheptaose as the substrate, and with brush border sucrase-isomaltase (with maltase, sucrase and isomaltase activities) derived from differentiated human intestinal Caco-2(/TC7) cells to assess hydrolysis of disaccharides. The wet-lab assay takes ~2-5 h depending on the number of samples, and the HPAE-PAD analysis takes 35 min per sample. A full dataset therefore takes 1-3 d and allows detection of subtle changes in enzyme activity with high sensitivity and reliability.

A single, high-fat meal adversely affects postprandial endothelial function: a systematic review and meta-analysis.

BACKGROUND: Endothelial dysfunction is a predictive risk factor for the development of atherosclerosis and is assessed by flow-mediated dilation (FMD). Although it is known that NO-dependent endothelial dysfunction occurs after consuming a high-fat meal, the magnitude of the effect and the factors that affect the response are unquantified. OBJECTIVES: We conducted a systematic review and meta-analysis exploring the quantitative effects of a single high-fat meal on endothelial function and determined the factors that modify the FMD response. METHODS: Six databases were systematically searched for original research published up to January 2022. Eligible studies measured fasting and postprandial FMD following consumption of a high-fat meal. Meta-regression was used to analyze the effect of moderator variables. RESULTS: There were 131 studies included, of which 90 were suitable for quantitative meta-analysis. A high-fat meal challenge transiently caused endothelial dysfunction, decreasing postprandial FMD at 2 hours [-1.02 percentage points (pp); 95% CI: -1.34 to -0.70 pp; P < 0.01; I2 = 93.3%], 3 hours [-1.04 pp; 95% CI: -1.48 to -0.59 pp; P < 0.001; I2 = 84.5%], and 4 hours [-1.19 pp; 95% CI: -1.53 to -0.84 pp; P < 0.01; I2 = 94.6%]. Younger, healthy-weight participants exhibited a greater postprandial reduction in the FMD percentage change than older, heavier, at-risk groups after a high-fat meal ( P < 0.05). The percentage of fat in the meals was inversely associated with the magnitude of postprandial changes in FMD at 3 hours (P < 0.01). CONCLUSIONS: A single, high-fat meal adversely impacts endothelial function, with the magnitude of the impact on postprandial FMD moderated by the fasting FMD, participant age, BMI, and fat content of the meal. Recommendations are made to standardize the design of future postprandial FMD studies and optimize interpretation of results, as high-fat meals are commonly used in clinical studies as a challenge to assess endothelial function and therapeutics. This trial was registered at PROSPERO as CRD42020187244.

Reduced Growth, Altered Gut Microbiome and Metabolite Profile, and Increased Chronic Kidney Disease Risk in Young Pigs Consuming a Diet Containing Highly Resistant Protein.

High-heat processed foods contain proteins that are partially resistant to enzymatic digestion and pass through to the colon. The fermentation of resistant proteins by gut microbes produces products that may contribute to chronic disease risk. This pilot study examined the effects of a resistant protein diet on growth, fecal microbiome, protein fermentation metabolites, and the biomarkers of health status in pigs as a model of human digestion and metabolism. Weanling pigs were fed with standard or resistant protein diets for 4 weeks. The resistant protein, approximately half as digestible as the standard protein, was designed to enter the colon for microbial fermentation. Fecal and blood samples were collected to assess the microbiome and circulating metabolites and biomarkers. The resistant protein diet group consumed less feed and grew to ~50% of the body mass of the standard diet group. The diets had unique effects on the fecal microbiome, as demonstrated by clustering in the principal coordinate analysis. There were 121 taxa that were significantly different between groups (adjusted-p < 0.05). Compared with control, plasma tri-methylamine-N-oxide, homocysteine, neopterin, and tyrosine were increased and plasma acetic acid was lowered following the resistant protein diet (all p < 0.05). Compared with control, estimated glomerular filtration rate (p < 0.01) and liver function marker aspartate aminotransferase (p < 0.05) were also lower following the resistant protein diet. A resistant protein diet shifted the composition of the fecal microbiome. The microbial fermentation of resistant protein affected the levels of circulating metabolites and the biomarkers of health status toward a profile indicative of increased inflammation and the risk of chronic kidney disease.

Ultraviolet radiation-induced degradation of dermal extracellular matrix and protection by green tea catechins: a randomized controlled trial.

BACKGROUND: Loss and remodelling of the dermal extracellular matrix (ECM) are key features of photodamaged human skin. Green tea catechins (GTCs) have been explored for their anti-inflammatory and chemopreventive properties, but data on the impact of GTCs on ultraviolet radiation (UVR)-induced changes to the dermal ECM are lacking. AIM: To investigate the effect of an inflammatory dose of solar-simulated UVR on human dermal ECM and potential for protection by GTCs in a double-blind randomized controlled trial. METHODS: In total, 50 healthy white (Fitzpatrick skin type I-II) adults aged 18-65 years were randomized to a combination of GTCs 540 mg plus vitamin C 50 mg or to placebo twice daily for 12 weeks. The impact of solar-simulated UVR at 3 × minimal erythema dose on the dermal collagen and elastic fibre networks was assessed by histology and immunohistochemistry in all participants at baseline. The impact of GTC supplementation on UVR-induced effects was compared between the groups post-supplementation. RESULTS: The area of papillary dermis covered by collagen and elastic fibres was significantly lower (P < 0.001) in UVR-exposed skin than in unexposed skin. Significantly lower levels of fibrillin-rich microfibrils (P = 0.02), fibulin-2 (P < 0.001) and fibulin-5 (P < 0.001) were seen in UVR-exposed than unexposed skin, while procollagen-1 deposition was significantly higher in UVR-exposed skin (P = 0.01). Following GTC supplementation, the UVR-induced change in fibulin-5 was abrogated in the active group but not the placebo group, with no difference between the two groups for other components. CONCLUSIONS: Acute UVR induced significant changes in the human dermal collagen and elastic fibre networks, whereas oral GTCs conferred specific UVR protection to fibulin-5. Future studies could explore the impact of GTCs on the effects of repeated suberythemal UVR exposure of human skin.

Effects of Polyphenols on Glucose-Induced Metabolic Changes in Healthy Human Subjects and on Glucose Transporters.

Dietary polyphenols interact with glucose transporters in the small intestine and modulate glucose uptake after food or beverage consumption. This review assesses the transporter interaction in vitro and how this translates to an effect in healthy volunteers consuming glucose. As examples, the apple polyphenol phlorizin inhibits sodium-glucose linked transporter-1; in the intestinal lumen, it is converted to phloretin, a strong inhibitor of glucose transporter-2 (GLUT2), by the brush border digestive enzyme lactase. Consequently, an apple extract rich in phlorizin attenuates blood glucose and insulin in healthy volunteers after a glucose challenge. On the other hand, the olive phenolic, oleuropein, inhibits GLUT2, but the strength of the inhibition is not enough to modulate blood glucose after a glucose challenge in healthy volunteers. Multiple metabolic effects and oxidative stresses after glucose consumption include insulin, incretin hormones, fatty acids, amino acids, and protein markers. However, apart from acute postprandial effects on glucose, insulin, and some incretin hormones, very little is known about the acute effects of polyphenols on these glucose-induced secondary effects. In summary, attenuation of the effect of a glucose challenge in vivo is only observed when polyphenols are strong inhibitors of glucose transporters.

Does timing of phytonutrient intake influence the suppression of postprandial oxidative stress? A systematic literature review.

BACKGROUND: Postprandial oxidative stress markers in blood are generated transiently from various tissues and cells following high-fat and/or high-carbohydrate (HFHC) meals, and may be suppressed by certain phytonutrients, such as polyphenols and carotenoids. However, the transient presence of phytonutrients in circulation suggests that timing of consumption, relative to the meal, could be important. This systematic review investigates the effect of timing of phytonutrient intake on blood markers of postprandial oxidative processes. METHOD: EMBASE, Medline, Scopus and Web of Science were searched up to December 2020. Eligible studies met the criteria: 1) healthy human adults; 2) phytonutrient(s) consumed in solid form within 24 h of a HFHC meal; 3) postprandial measurements of oxidative stress or antioxidants in blood; and 4) controlled study design. Cohen's d effect sizes were calculated to compare studies. RESULTS: Nine studies, involving 256 participants, were included. Phytonutrients were consumed either at the same time, 1 h before, or the day (>12 h) before a HFHC meal. Significant decreases in blood markers - plasma lipid hydroperoxides, plasma malondialdehyde, serum sNox2-dp, serum 8-iso-PGF2α, platelet p47phox phosphorylation, and Keap-1 and p47phox protein levels in mononuclear cells (MNCs) - were observed where the phytonutrient was consumed together with the challenge meal (n = 4). Lack of any effect on oxidative stress markers was observed where phytonutrients were consumed with (n = 1), 1 h before (n = 1), and the day before (n = 2) the HFHC meal. CONCLUSION: Phytonutrients consumed with a HFHC meal significantly suppressed some markers of oxidative stress in blood. Although there were only a limited number of studies, it appears that suppression appeared effective at the time of peak phytonutrient concentration in plasma. However, further studies are required to confirm the observations and systematically optimise the effect of timing.