Nearly half of all Australians (42.9%) will experience a mental health disorder during their lifetime (1) . Preliminary research suggests an association between dietary and tissue advanced glycation end-products (AGEs) and mental health conditions, such as depression (2,3) . However, more research is needed to determine the extent to which poor mental health is linked with AGEs (4) . This study examined whether dietary consumption of the AGE carboxymethyl-lysine (CML), tissue accumulation of AGEs, or levels of circulating glycated haemoglobin (HbA1c) were associated with depression or anxiety. Fifty adults participated in a cross-sectional study. Depression and anxiety were assessed using the Centre for Epidemiologic Studies Depression Scale (CES-D) and Spielberger’s State-Trait Anxiety Inventory (STAI). Dietary CML intake was assessed from 3-day food records by matching food items to those in published, validated food AGE databases and adjusting for energy intake (CML/MJ). Tissue accumulation of AGEs was measured as skin autofluorescence (SAF) using an AGE Reader. HbA1c was measured in whole blood using a Capillary 3 HbA1c kit. Spearman’s rank correlations were performed to explore relationships between variables. Participants included 14 males and 36 females, aged (median (range)) 30.6 (18–72) years. Participants were predominantly healthy, with a BMI of 23.3 (18.5–31.1) kg/m 2 and energy intake of 7889 (5452–12568) kJ/day. Depression scores were 8 (0–40) out of 60. State anxiety scores were 26 (20–53) and trait anxiety scores were 33.5 (20–66) out of 80, where higher scores indicated greater symptom severity. Daily intake of CML was 0.6 (0.2–1.9) mg/MJ/day. SAF was 1.8 (1.2–3.3) arbitrary units (AU), similar to previously reported normal reference values (5) . Circulating HbA1c was 5.1% (4.4–6.2%), all within the healthy range (6) . Spearman’s correlation tests indicated no significant associations between any of the independent variables (CML/MJ, SAF, HbA1c) and any of the dependent variables (CES-D, STAI) (all p > 0.05). In this population of predominantly of healthy individuals, there was no association between dietary CML intake, tissue AGE accumulation or circulating HbA1c and increased symptom severity for depression or anxiety. The next step of this research is to investigate metabolomic markers in this population and their association with depression and anxiety. In relatively healthy people, dietary metabolites may be more sensitive to uncover whether a relationship exists between AGEs and depression and anxiety.

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.

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 mismatched 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.

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.

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.

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 ∼51% 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.

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.

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 mu M at 4 C and 64.2 +/- 7.6 mu M at 20 degrees 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 mu M after 1 day and declined to 42-60 mu M (4 degrees C) or zero after-10 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.

The salt content of sausage needed for microbial preservation is typically >2% (w/w); however, it is desirable to decrease the salt content of foods because of associated adverse effects on cardiovascular health. It was hypothesized that high pressure processing (HPP) applied pre-cooking (100-400 MPa at 10 degrees C for 15 min), in combination with lowering the salt content of emulsified sausage (1.4%, w/w), could achieve microbial stability. Effects of HPP/low salt conditions on microbiological, physicochemical, color, texture and sensory properties of beef sausage were studied, and compared with no-HPP control conditions (2.8% salt, w/w, C1) and 1.4% salt, w/ w, C2). Microbiological quality was evaluated by total viable counts (TVCs) and changes in counts of selected micro-organisms. Physicochemical parameters studied included: protein quality, pH, moisture loss after cooking, total volatile basic nitrogen (TVBN), thiobarbituric acid reactive substances (TBARS), colour and texture analyses. Sensory parameters studied included consumer evaluation of flavor and texture. The myofibrillar protein extracted from HPP-treated, pre-cooked sausage was characterized for solubility, carbonyl and total sulfhydryl contents. The results showed that lower salt, in combination with HPP-treatment, produced TVCs equivalent to the C1 conditions. In addition, HPP treatment affected other measured parameters, with treatment at 200 MPa producing physicochemical properties similar to C1 conditions, and achieved textural and sensory attributes preferred by consumers. Sensory and textural properties of sausages decreased for HPP treatments >= 300 MPa. To conclude, HPP shows promise as a processing method for achieving microbial preservation of sausages with lower salt content, and with acceptable sensory properties.

Milk represents a challenging matrix to study and process because of its compositional complexity and variability. Small variations in concentrations of macro- and micro-nutrients are present in raw milk from a given species, while large variations occur between milks from different species. The processing of milk represents the opportunity to standardize its chemical composition and to control, diversify and innovate the functional properties of products. The basis of industrial processing and understanding functional properties is largely derived from researching cow milk. However, the dairy industry increasingly includes mammalian milks from species other than cow. The knowledge for processing cow milk is applicable to other milks but the translation of the broad base of dairy research is inhibited by the lack of reporting of absolute physicochemical measures that can be compared between studies and in particular, between cow and non-cow milks.

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.

Abstract Alzheimer’s disease (AD) is the most common cause of dementia. Its pathology is primarily characterized by extracellular deposits of amyloid β 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.

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.

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.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.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.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.

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-PGF2 alpha, 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.

Abstract Alzheimer’s disease, resulting from the over-expression of amyloid precursor protein (APP) and accumulation of plaques comprising the APP-derived amyloid beta (Aβ), is a diagnostic and pathological brain feature of Alzheimer’s disease (AD). For older, predisposed people, accumulation of Aβ plaque in the brain precedes symptoms of memory loss by decades. There is a growing consensus that over-expression of APP may also reflect a defense response against infection, via the antibiotic effects of Aβ, which becomes toxic when Aβ peptides cannot be cleared from the brain. These scenarios permit two possible pathways of potential intervention from whey proteins mediated by lactoferrin and hydrolyzed whey proteins. In particular, the interference of fibril assembly whey-derived peptides can promote opportunity for clearance of aggregating forms of Aβ, while the anti-microbial activity of whey proteins such as lactoferrin have potential to suppress the activity of microbes (and viruses) and collectively manage the progress of AD. This presentation will explain the individual potential benefits of whey peptides and lactoferrin, based on available evidence. More research is required to determine if a synergistic effect might be possible from this therapeutic combination.

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.

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 mu M 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 mu M/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.