The role of microbial infection in the pathogenesis of Alzheimer's disease and the opportunity for protection by anti-microbial peptides.

Alzheimer's disease (AD) is the most common cause of dementia. Its pathology is primarily characterized by extracellular deposits of amyloid ß peptide and intracellular neurofibrillary tangles. Current rationales to explain the pathogenesis of AD include amyloid cascade, inflammation, infection defense and anti-microbial protection hypotheses. This review focuses on recent advances in the infection hypothesis, in particular on those pathogenic microbes that act systemically, via periodontal and gastro-intestinal infection routes. It is proposed that the evidence convincingly supports that pathogenic microbial infection is associated with, and is likely a causative trigger for, AD pathology. Microbes can drive AD pathology by two main pathways: either by directly infecting the brain and stimulating amyloid-mediated defence (causative trigger) or indirectly, by stimulating the pro-inflammatory effects of infection. In this context, it follows that anti-microbial/anti-infection therapies could be effective for regulating the pathology and symptoms of AD, depending on the stage of disease. As long-term administration of traditional antibiotic therapy is not recommended, alternative antibiotic agents such as anti-microbial peptides (AMPs), could be preferred for intervention and disease management of AD.

Inhibition of Angiotensin Converting Enzyme, Angiotensin II Receptor Blocking, and Blood Pressure Lowering Bioactivity across Plant Families.

Hypertension is a major risk factor for coronary heart disease, kidney disease, and stroke. Interest in medicinal or nutraceutical plant bioactives to reduce hypertension has increased dramatically. The main biological regulation of mammalian blood pressure is via the renin-angiotensin-aldosterone system. The key enzyme is angiotensin converting enzyme (ACE) that converts angiotensin I into the powerful vasoconstrictor, angiotensin II. Angiotensin II binds to its receptors (AT1) on smooth muscle cells of the arteriole vasculature causing vasoconstriction and elevation of blood pressure. This review focuses on the in vitro and in vivo reports of plant-derived extracts that inhibit ACE activity, block angiotensin II receptor binding and demonstrate hypotensive activity in animal or human studies. We describe 74 families of plants that exhibited significant ACE inhibitory activity and 16 plant families with potential AT1 receptor blocking activity, according to in vitro studies. From 43 plant families including some of those with in vitro bioactivity, the extracts from 73 plant species lowered blood pressure in various normotensive or hypertensive in vivo models by the oral route. Of these, 19 species from 15 families lowered human BP when administered orally. Some of the active plant extracts, isolated bioactives and BP-lowering mechanisms are discussed.

In vitro heme and non-heme iron capture from hemoglobin, myoglobin and ferritin by bovine lactoferrin and implications for suppression of reactive oxygen species in vivo.

Lactoferrin (Lf), present in colostrum and milk is a member of the transferrin family of iron-binding glyco-proteins, with stronger binding capacity to ferric iron than hemoglobin, myoglobin or transferrin. Unlike hemoglobin and myoglobin, iron-bound Lf is reasonably stable to gastric and duodenal digestive conditions. Unlike ferrous iron, ferric iron is not directly reactive with oxygen supporting the capacity of Lf capture of heme iron to suppress reactive oxygen species (ROS) production. We therefore hypothesized that bovine Lf could capture and thereby terminate the cycle of ROS production by heme iron. The transfer of heme iron from either intact or digested forms of hemoglobin and myoglobin and from intact ferritin was demonstrated by in vitro methods, monitoring Fe-saturation status of Lf by changes in absorptivity at 465 nm. The results are discussed in the context of new proposed opportunities for orally administered Lf to regulate oxidative damage associated with heme iron. In addition to potentially suppressing oxidative heme-iron-mediated tissue damage in the lumen, Lf is expected to also reverse the overload of ferritin-bound iron, that accompanies chronic inflammation and aging. These new proposed uses of Lf are additional to known host defense functions that include anti-microbial, anti-viral properties, immune and cancer cell growth regulation. The findings and interpretations presented require clinical substantiation and may support important additional protective and therapeutic uses for Lf in the future.

Exome-informed formulations of food proteins enhance body growth and feed conversion efficiency in ad libitum-fed mice.

Meeting requirements for dietary proteins, especially of essential amino acids (EAAs), is critical for the life-long health of living organisms. However, defining EAA targets for preparing biologically-matched nutrition that satisfies metabolic requirements for protein remains challenging. Previous research has shown the advantages of 'exome matching' in representing the specific requirement of dietary AAs, where the target dietary AA profile was derived from in silico translation of the genome of an organism, specifically responsible for protein expression (the 'exome'). However, past studies have assessed these effects in only one sex, for few parameters (body mass and composition), and have used purified diets in which protein is supplied as a mixture of individual AAs. Here, for the first time, we utilise a computational method to guide the formulation of custom protein blends and test if exome matching can be achieved at the intact protein level, through blending standard protein ingredients, ultimately leading to optimal growth, longevity and reproductive function. Mice were provided ad libitum (ad lib) access to one of the four iso-energetic protein-limited diets, two matched and two mis-matched to the mouse exome target, and fed at a fixed protein energy level of 6.2%. During or following 13-weeks of feeding, the food intake, body growth, composition and reproductive functions were measured. Compared to the two mis-matched diets, male and female animals on the exome-matched diet with protein digestibility correction applied, exhibited significantly improved growth rates and final body mass. The feed conversion efficiency in the same diet was also increased by 62% and 40% over the worst diets for males and females, respectively. Male, not female, exhibited higher accretion of lean body mass with the matched, digestibility-corrected diet. All reproductive function measures in both sexes were comparable among diets, with the exception of testicular daily sperm production in males, which was higher in the two matched diets versus the mis-matched diets. The results collectively demonstrate the pronounced advantages of exome-matching in supporting body growth and improving feed conversion efficiency in both sexes. However, the potential impact of this approach in enhancing fertility needs further investigation.

Regulation of milk protein solubility by a whey-derived proline-rich peptide product.

The effects of a bovine whey peptide product enriched in proline (wPRP) on the solubility of milk proteins were tested under ambient conditions or following heat treatment at 75 and 100 °C, for 1 and 15 min, followed by post-incubation storage at either ambient temperature or 4 °C for up to 7 d. wPRP promoted solubilisation of milk proteins in a concentration-dependent manner without heat treatment and also after heat treatment at 75 and 100 °C, and the effect was enhanced after storage under either ambient or refrigerated storage conditions. Interactions of wPRP and milk proteins were monitored by particle size analysis and tryptic digestion and specifically linked with solubilisation of αS1 casein (αS1-Cn), which supported observed changes in milk protein solubility. The results suggested that wPRP preferably prevented or reversed physical versus covalent protein aggregation, with the relaxation of hydrophobic interactions at 4 °C providing an additive effect. This application of wPRP represents a novel approach to stabilisation of dairy proteins following thermal processing with industrial usefulness yet to be explored.

Comparative yields of antimicrobial peptides released from human and cow milk proteins under infant digestion conditions predicted by in silico methodology.

Mammalian milk proteins are known to encrypt antimicrobial peptides (AMPs) which can be passively released and exert bioactivity in the gastrointestinal and cardiovascular systems pre- or post-absorption, respectively. However, the contribution of 'passive' food-derived AMPs to the pool of endogenous and microbial AMPs has not been differentiated in previous research. Insight into the consequences of protein digestion and peptide bioactivity can be gained using in silico tools. The aim of this investigation was to use in silico methods to characterise the yields of AMPs released from major proteins in human and cow milk under infant digestion conditions, as relevant to early nutrition. The profiles of major proteins in human and cow milk from UniProtKB/Swiss-Prot, were subjected to in silico digestion by ExPASy-PeptideCutter, and the AMP activity of resulting peptides (≥4 amino acids, AAs) evaluated with the CAMPR3-RF predictive tool. The mass yields and counts of absorbing (≤10 AAs) and non-absorbing (>10 AAs) AMPs, as found in human, cow and 'humanised' ratios of cow milk proteins, were quantified. The results indicated that major whey proteins from both human and cow milks displayed a higher degree of hydrolysis than caseins, consistent with their known 'fast' digestion properties. Larger albumin and lactoferrin proteins generated relatively more and/or longer peptides. Yields of AMPs from cow milk were higher than from human milk, even after standardising the ratio of whey to casein and total protein concentration, as practiced in formulations manufactured for human newborn babies. Whereas alpha-lactalbumin (2.65 g L-1) and lactoferrin (1.75 g L-1) provided the major yields of AMPs in human milk whey proteins; beta-lactoglobulin, which is unique to cow milk, released the highest yield of AMPs in cow milk (3.25 g L-1 or 19.9% w/w of total whey protein), which may represent an important and overlooked biological function of this protein in cow milk.

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.

Demonstration of anti-oxidant properties of mustard seed (Brassica juncea) protein isolate in orange juice.

Previous research has shown that formulated and natural beverages containing mixtures of anti-oxidants can produce stable levels of hydrogen peroxide (H2O2). The aim of this study was to demonstrate the ultimate anti-oxidant effects of proteins for suppressing H2O2, using a protein extract from mustard seed (Brassica juncea). The mustard seed protein isolate (MPI) contained âˆ¼51% protein, and 6.4 mg GAe/g TS of total reducible substances, presumably representing secondary metabolites, including polyphenolics. Dose-dependent suppression of H2O2 (present at 110 µM and 550 µM), in fresh and thermally-processed orange juice was complete in the presence of 0.1 mg/mL MPI after 24 hr, with slightly higher anti-oxidant efficacy than the fruit juice-derived reference protein, thaumatin. The combination of thiol-rich amino acid (methionine and cysteine)-containing proteins and other anti-oxidant species in the MPI were highly effective for inhibiting autoxidation-mediated production of H2O2 in orange juice, and may be useful for other manufactured beverages.

Production of hydrogen peroxide in commercial orange juice products is related to proximate composition, processing conditions and storage time.

Based on the observed production of H2O2 in formulated beverages containing artificial or 'non-natural' mixtures of anti-oxidants (AOXs), it was hypothesized that the natural redox-active compounds present in orange juice (OJ) might also produce H2O2. Here, we report the levels of H2O2 found in commercially manufactured OJ products in 'fresh' (4 °C on-shelf storage, N = 9) and 'processed' (ambient on-shelf storage, N = 9) categories. The average concentrations of H2O2 immediately after opening the container (T0) were significantly higher (p < 0.01) in processed (11.15 ± 2.83 µM) versus fresh (3.74 ± 2.02 µM) sample sets. Levels of H2O2 at T0 were uncorrelated with storage time post-manufacture and increased after opening (1 to 4-fold), followed by significant decrease after 24 hr (p < 0.05). Using Pearson's correlation analysis; ascorbic acid, total reducible substances and total sugar were each significantly positively correlated, while total protein, fibre and unsaturated fats were each significantly negatively correlated, with H2O2 levels in OJs.

Formulations of selected Energy beverages promote pro-oxidant effects of ascorbic acid and long-term stability of hydrogen peroxide.

Recently, autoxidation mediated by ascorbic acid (AA) and other ingredients, has been implicated in generation of hydrogen peroxide (H2O2) in so-called Energy beverages. Here, we report the use of cyclic voltammetry and the FOX assay to monitor at short and long incubation times, respectively, the production and stability of H2O2 generated by AA and redox-active ingredients. Levels of H2O2 in Energy drinks (36.5 ± 4.0 µM at 4 °C and 64.2 ± 7.6 µM at 20 °C) were found to be stable or increased (p < 0.05) upon vessel opening. A predictive model for the production of H2O2 as a function of AA concentration, temperature and incubation time, and depending on ingredients present, indicated that H2O2 peaked at 91-726 µM after 1 day and declined to âˆ¼ 42-60 µM (4 °C) or zero after âˆ¼10 days. The research supports that levels of H2O2 in beverages containing anti-oxidant mixtures and dissolved oxygen should be monitored and formulations modified to avoid AA autoxidation.

Relaxation Effects of Essential Oils Are Explained by Their Interactions with Human Brain Neurotransmitter Receptors and Electroencephalography Rhythms.

Inhaled essential oils (EOs) are bioavailable to the brain and are consistently reported to promote relaxation effects. Their mechanisms of action are however not well understood. The aim of this investigation was to assess the neuroactivity of EOs based on their (i) binding interactions to neurotransmitter receptors and (ii) bioelectrical activities in the brain as measured by electroencephalography (EEG). These EO properties were compared to those of reference pharmaceutical compounds with effects also measured by EEG. Relative receptor binding efficacies of 10 reference compounds, 180 EOs, and 9 EO extracts with 7 different neurotransmitter receptors were calculated using in silico molecular docking procedures. Changes in brain EEG rhythms, as standardized changes in absolute power, were determined for the reference compounds and selected EOs and compared to receptor binding efficacy results. The reference compounds had diverse receptor binding patterns, with EEG responses dominated by EEG-delta wave frequencies. In contrast, the receptor binding pattern of the EOs was remarkably consistent and replicated a subclinical affinity pattern corresponding to the inhibitory glycine-α-GLRA3 and dopamine-D2 receptors, producing responses dominated by EEG-alpha wave frequencies. The results support the hypothesis that EOs stimulate neuroactivity by modulating patterns of neurotransmission affecting alpha wave EEG responses.

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.

Micronutrient mineral and folate content of Australian and imported dried fruit products.

A selection of Australian and imported fresh and dried fruit products, including sultanas, Sunmuscats, Carina currants, Zante currants, apricots, and prunes, were analyzed for selected minerals (Ca, Mg, Na, S, B, Al, Fe, Mn, Cu, Zn, Mo, and Se), folate and vitamin C, and the capacity of dried fruits for dietary provision of these micronutrients evaluated. Micro-nutrients were concentrated by a factor of 3-5 in dried fruits compared with their fresh fruit counterparts and were consequently present in nutritionally significant levels, in contrast to fresh fruit. Australian dried sultanas, Carina currant, Zante currant, apricots, and prunes contained Cu, Fe, K, and Mn at levels of >20% of daily Required Dietary Intake (RDI, taken as the average for adult men and women as nominated by the Australian National Health and Medical Research Council) and Sunmuscats contained Cu, Fe, and K at >20% of RDI. All dried fruits studied contained boron in the range of 1.5 to 5.4 mg per 100 g; however, the RDI for boron has not been defined by the NHMRC at the present time. All sultanas and currants studied contained folate at levels of 10-20% of RDI per 100 g. Experimental drying methods significantly affected folate levels with higher folate content in non-ground versus ground-based drying methods. Of the micro-nutrients supplying >20% of RDI, folate represents a particular nutrient for which the mean daily intake of adult Australians is typically inadequate. This study shows that dried fruit consumption, in contrast with fresh fruit, can provide significant proportions of daily requirements of several micronutrients, particularly folate.

Anxiolytic effects of essential oils may involve anti-oxidant regulation of the pro-oxidant effects of ascorbate in the brain.

Essential oils (EOs) absorbed via inhalation are consistently reported to produce anxiolytic effects. The underlying neurochemical mechanisms, however, are not well understood. High concentrations of ascorbate in the human brain (~10 mM in neurons) implicates this compound as a key signaling molecule and regulator of oxidative stress. In this study, we demonstrate the significant in vitro capacity of ascorbate to produce H2O2 in the presence of oxygen at physiological pH values, peaking at ~400 µM for ascorbate levels of 1.0 mg/mL (5.6 mM). In comparison, individual EOs and selected neurotransmitters at similar concentrations produced <100 µM H2O2. Systematic studies with binary and ternary mixtures containing ascorbate indicated that EOs and neurotransmitters could variably enhance (pro-oxidant, POX) or suppress (anti-oxidant, AOX) the production of H2O2 versus the ascorbate control, depending on the concentration ratios of the components in the mixture. Moreover, the AOX/POX chemistry observed with binary mixtures did not necessarily predict effects with ternary mixtures, where the POX ascorbate chemistry tended to dominate. A model is proposed to account for the ability of compounds with electron-donating capacity to catalytically regenerate ascorbate from intermediate oxidized forms of ascorbate, thus driving H2O2 production and exerting a net POX effect; whilst compounds that irreversibly reacted with oxidized forms of ascorbate suppressed the production of H2O2 and produced an overall AOX effect. Since the anxiolytic effects of different EOs, including extracts of Lavendula angustifolia (lavender) and Salvia rosmarinus (rosemary), were associated with AOX regulation of H2O2 production by ascorbate, it can be concluded that these anxiolytic effects are potentially related to the AOX properties of EOs. In contrast, EOs driving POX effects (eg, Junipenus communis (Juniper) berry EO) are proposed to be more useful for their potential anti-microbial or cancer cytotoxic applications.

Production of hydrogen peroxide in formulated beverages is associated with the presence of ascorbic acid combined with selected redox-active functional ingredients.

Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that mediates essential signaling in vivo but may cause irreversible tissue damage under dysregulated or acute exposure conditions. Beverages containing redox-active compounds might produce H2O2 during shelf storage and potentially be consumed. Concentrations of H2O2 in selected 'functional' (including energy, E, n = 28), 'non-functional' flavored, (S, n = 6) and mineral water (W, n = 6) drinks were measured under ambient (i.e., produced in situ) and 'potentiated' conditions (i.e., H2O2 production enhanced by addition of a reducing agent, to simulate availability of reducible substrates in vivo). Under air-saturated conditions, mean H2O2 contents were: 15.60 ± 15.84; 1.39 ± 2.06 and 0.30 ± 0.21 µM in E, S and W drinks, respectively. Under air-saturated, potentiated conditions, mean rates of H2O2 production were 21.7 ± 33.3, 0.98 ± 2.84, and -0.38 ± 1.18 µM/h for E, S and W drinks, respectively. Using multivariate statistics, the ingredient significantly associated with H2O2 production in combination with other ingredients was found to be ascorbic acid.

Dose-related effects of inhaled essential oils on behavioural measures of anxiety and depression and biomarkers of oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Essential oils (EOs) are extracts of organic, volatile metabolites of plants that are typically oily liquids at ambient temperatures. Inhalation of EOs can regulate brain health and functions associated with mood and neurodegeneration, reflecting their bioavailability to brain. The aim was to identify physicochemical properties that influenced EO volatility and pathways of brain uptake by inhalation. MATERIALS AND METHODS: Dose-dependency of effects, determined as: total EO intake (µg/g bodyweight-BW), and rate of EO intake (µg/hr/g-BW), was determined by meta-analysis of data from animal studies (10 studies, 12 EOs), measuring effects on anxiety, depression and selected biomarkers of oxidative stress and inflammation (OSI). RESULTS: Results demonstrated benefits on animal behavior at EO intakes of 1-100 µg/g BW and 1-10 µg/hr/g BW (Elevated Plus Maze and Forced Swimming tests) and <100 µg/g BW and 10-100 g/hr/g BW (Marble Burying). EOs regulated OSI biomarkers at intakes of 10-100 µg/g BW and 1-10 µg/h/g BW, and a dose-dependent elevation of dopamine at >1000 µg/g BW and 100-1000 µg/hr/g BW. CONCLUSION: The results support that EO 'aromatherapy' can promote dose-dependent regulation of anxiety, depression and OSI and that efficacy requires optimization of dose.

Characterising absorption and health-related properties of phytochemicals extracted from Malaysian palm fruit biomass after oil extraction.

After oil extraction, palm fruit biomass contains abundant water-soluble phytochemicals (PCs) with proven bioactivity in regulating oxidative stress and inflammation (OSI). For optimal bioefficacy following oral consumption, the pharmacokinetic plasma peak (Tmax) should be bio-matched with the onset of OSI, which can be predicted from the Phytochemical Absorption Prediction (PCAP) model and methodology. Predicted absorption and potential for regulation of OSI by measures of total phenolic content, antioxidant capacity and hydrogen peroxide production capacity, were applied to characterise eight extracts from mesocarp fibre and kernel shells of oil-depleted palm fruits. Results indicated post-consumption absorption Tmax ranges of 0.5-12 h and 2-6 h for intake in liquid and solid forms, respectively, and generally high antioxidant activity of the extracts. The research supports that PC extracts of palm fruit biomass have broad potential uses for human health as dietary antioxidants in foods, supplements or functional beverages.

Effects of macro-nutrient, micro-nutrient composition and cooking conditions on in vitro digestibility of meat and aquatic dietary proteins.

Animal and aquatic meats represent important sources of dietary protein and micro-nutrients. Although red and processed meats carry some risks for human health, sensory and nutritional advantages drive meat consumption. Therefore, it is important to understand how meat processing and cooking influence healthiness. The research aim was to investigate relationships of meat composition (proximates, amino acids and minerals) and cooking conditions (raw, 90 s microwave, 200 °C oven for 10 or 30 min) on protein digestibility, for a selection of four animal (beef, chicken, pork, kangaroo) and four aquatic meats (salmon, trout, prawn, oyster). Lean meats were minced before cooking followed by in vitro gastro-intestinal digestion and analysed for progress of hydrolysis, and size ranges of peptides using MALDI-TOF-MS. Correlation matrix analysis between compositional and functional parameters indicated that digestibility was significantly linked with protein and metal concentrations, likely reflecting moisture-dependent solubility and inter-mixing of sarcoplasmic metallo-proteins and insoluble myofibrillar proteins.

Effects of chemical composition and baking on in vitro digestibility of proteins in breads made from selected gluten-containing and gluten-free flours.

Breads prepared from cereal grains are a dietary staple, providing a significant proportion of daily energy, but not necessarily of dietary protein. However, good digestibility of proteins in bread is important to avoid potential immunogenic effects of undigested peptides, including for those gluten-intolerant. Four gluten-containing (white wheat, wholemeal wheat, spelt and rye) and four gluten-free (chick pea, lupin, buckwheat, amaranth) flours were used to make yeast-leavened breads standardized for protein. In vitro gastro-intestinal digestion of pre-mixes, doughs and breads baked for 20 and 35min was conducted followed by correlation analysis between fitted parameters of digestion profiles, chemical composition (protein, non-fibre carbohydrates, fibre, ash and total polyphenolics) and amino acid profiles. The results indicated that digestibility generally increased during proofing and decreased during baking. Relatively higher protein digestibility was correlated with ratio of non-fibre carbohydrate to protein and lower digestibility with increasing contents of fibre and total polyphenolics in pre-mixes.

Physicochemical properties of dietary phytochemicals can predict their passive absorption in the human small intestine.

A diet high in phytochemical-rich plant foods is associated with reducing the risk of chronic diseases such as cardiovascular and neurodegenerative diseases, obesity, diabetes and cancer. Oxidative stress and inflammation (OSI) is the common component underlying these chronic diseases. Whilst the positive health effects of phytochemicals and their metabolites have been demonstrated to regulate OSI, the timing and absorption for best effect is not well understood. We developed a model to predict the time to achieve maximal plasma concentration (Tmax) of phytochemicals in fruits and vegetables. We used a training dataset containing 67 dietary phytochemicals from 31 clinical studies to develop the model and validated the model using three independent datasets comprising a total of 108 dietary phytochemicals and 98 pharmaceutical compounds. The developed model based on dietary intake forms and the physicochemical properties lipophilicity and molecular mass accurately predicts Tmax of dietary phytochemicals and pharmaceutical compounds over a broad range of chemical classes. This is the first direct model to predict Tmax of dietary phytochemicals in the human body. The model informs the clinical dosing frequency for optimising uptake and sustained presence of dietary phytochemicals in circulation, to maximise their bio-efficacy for positively affect human health and managing OSI in chronic diseases.