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Aim: Accumulation of circulating branched-chain amino acids (BCAA) is a hallmark feature of impaired insulin sensitivity. As intracellular BCAA catabolism is dependent on glycine availability, we hypothesised that the concurrent measurement of circulating glycine and BCAA may yield a stronger association with markers of insulin sensitivity than either BCAA or glycine alone. This study therefore examined the correlative relationships of BCAA, BCAA and glycine together, plus glycine alone on insulin sensitivity-related markers before and after an 8-week low energy diet (LED) intervention., Methods: This is a secondary analysis of the PREVIEW (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World) Study New Zealand sub-cohort. Eligible participants with pre-diabetes at baseline who achieved ≥8 % body weight loss following an LED intervention were included, of which 167 paired (Week 0 and Week 8) blood samples were available for amino acid analysis. Glycemic and other data were retrieved from the PREVIEW consortium database. Repeated measures linear mixed models were used to test the association between amino acids and insulin sensitivity-related markers (HOMA2-IR, glucose, insulin, and C-peptide)., Results: Elevated BCAA was associated with impaired insulin sensitivity (p < 0.05), with strength of association (ηp2) almost doubled when glycine was added to the model. However, glycine in isolation was not associated with insulin sensitivity-related markers. The magnitude (β-estimates) of positive association between BCAA and HOMA2-IR, and inverse association between glycine and HOMA2-IR, increased when body weight was higher (Body weight∗BCAA, Body weight∗glycine, p < 0.05, both)., Conclusion: Low serum glycine strengthened the association between BCAA and impaired insulin sensitivity. Given that glycine is necessary to facilitate intracellular BCAA catabolism, measurement of glycine is necessary to complement BCAA analysis to comprehensively understand the contribution of amino acid metabolism in insulin sensitivity., Clinical Trial Registration: This study was registered with ClinicalTrials.gov (NCT01777893)., Competing Interests: Conflict of interest SDP was the Fonterra Chair in Human Nutrition during the PREVIEW intervention; AR has received honorariums from Nestle, Unilever and the International Sweeteners Association. Other authors declare no relevant competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: A healthy diet has been proposed to support good mental health, but the addition of either red meat or meat alternatives is nuanced., Objectives: We aimed to determine if psychological and physiological well-being is differentially affected by consuming recommended weekly amounts of either lean red meat or plant-based meat alternatives (PBMAs) supplemented with a plant-rich diet., Methods: The trial was a parallel 2-arm randomized intervention of 10 wk duration. Eighty healthy omnivorous young adults were clustered as 40 cohabitating household pairs. Each pair was randomly assigned to consume 3 weekly servings of either fresh New Zealand beef and lamb or the equivalent PBMA. They maintained an otherwise ovo-lacto vegetarian diet, aided by a weekly meal kit and supported by engaged advice from research dietitians. Psychological measures were well-being (World Health Organization-Five Well-Being Index); depression, anxiety, and stress (depression anxiety stress scales-short form-21); and fatigue (multidimensional fatigue symptom inventory-short form) assessed weekly throughout the trial. Blood biomarkers included neurotransmitter-related compounds, iron status and vitamins B12 and D. Physical activity and sleep were estimated by a fitness wristband. Mixed effect modeling evaluated changes in each outcome over time relative to its baseline and compared the 2 interventions accounting for randomization unit clustering., Results: Thirty-nine household pairs completed the trial. Participants measured as psychologically healthy at baseline. There were no significant differences between groups in the degree of change from baseline for the psychological outcomes, nor for the majority of the circulatory markers. Differences in changes to vitamin B12 status and 3 neurotransmitter-related compounds (adenosine, agmatine, and tyrosine) from baseline to week 10 were observed between groups. Results were similar in all sensitivity analyses when adjusting for physical activity, sleep, and diet quality covariates., Conclusions: There was no effect on the psychological measures and limited change to physiological status when comparing a balanced diet containing either red meat or PBMAs in healthy young adults., Competing Interests: The study was partially funded by industry trade associations that represent companies supplying almost all of New Zealand meat exports. Those organizations did not have influence on the research design, data collection, or write up. The organizations also had no input into the writing of the publication nor did they have a right of refusal concerning publication (authors can provide contractual evidence to any interested party on request). The data analysis was conducted by an independent biostatistician (JH)., (© 2024 The Authors.)

Community screening for sarcopenia is complex, with barriers including access to specialized equipment and trained staff to conduct body composition, strength and function assessment. In the current study, self-reported dietary protein intake and physical activity (PA) in adults ≥65 years was assessed relative to sarcopenia risk, as determined by body composition, strength and physical function assessments, consistent with the European Working Group on Sarcopenia in Older People (EWGSOP) definition. Of those screened ( n = 632), 92 participants (77% female) were assessed as being at high risk of developing sarcopenia on the basis of dietary protein intake ≤1 g∙kg -1 ∙day -1 [0.9 (0.7-0.9) g∙kg -1 ∙day -1 ] and moderate intensity physical activity <150 min.week -1 . A further 31 participants (65% female) were defined as being at low risk, with both protein intake [1.2 (1.1-1.5) g∙kg -1 ∙day -1 ] and PA greater than the cut-off values. High-risk participants had reduced % lean mass [53.5 (7.8)% versus 54.8 (6.1)%, p < 0.001] and impaired strength and physical function. Notably, high-risk females exhibited greater deficits in lean mass and strength, with minimal differences between groups for males. In community-dwelling older adults, self-reported low protein intake and low weekly PA is associated with heightened risk for sarcopenia, particularly in older women. Future research should determine whether early intervention in older adults with low protein intake and PA attenuates functional decline.

Background: Vitamin B inadequacies and elevated homocysteine status have been associated with impaired cognitive and cardiometabolic health with aging. There is, however, a scarcity of research investigating integrated profiles of one-carbon (1C) metabolites in this context, including metabolites of interconnected folate, methionine, choline oxidation, and transsulfuration pathways., Objectives: The study aimed to examine associations between vitamins B and 1C metabolites with cardiometabolic health and cognitive function in healthy older adults, including the interactive effects of Apolipoprotein E-ε4 status., Methods: Three hundred and thirteen healthy participants (65-74 y, 65% female) were analyzed. Vitamins B were estimated according to dietary intake (4-d food records) and biochemical status (serum folate and vitamin B 12 ). Fasting plasma 1C metabolites were quantified by liquid chromatography with tandem mass spectrometry. Measures of cardiometabolic health included biochemical (lipid panel, blood glucose) and anthropometric markers. Cognitive function was assessed by the Computerized Mental Performance Assessment System (COMPASS) and Montreal Cognitive Assessment (MoCA). Associations were analyzed using multivariate linear (COMPASS, cardiometabolic health) and Poisson (MoCA) regression modeling., Results: Over 90% of participants met dietary recommendations for riboflavin and vitamins B 6 and B 12 , but only 78% of males and 67% of females achieved adequate folate intakes. Higher serum folate and plasma betaine and glycine concentrations were associated with favorable cardiometabolic markers, whereas higher plasma choline and homocysteine concentrations were associated with greater cardiometabolic risk based on body mass index and serum lipids concentration values (P< 0.05). Vitamins B and homocysteine were not associated with cognitive performance in this cohort, though higher glycine concentrations were associated with better global cognitive performance (P = 0.017), episodic memory (P = 0.016), and spatial memory (P = 0.027) scores. Apolipoprotein E-ε4 status did not modify the relationship between vitamins B or 1C metabolites with cognitive function in linear regression analyses., Conclusions: Vitamin B and 1C metabolite profiles showed divergent associations with cardiometabolic risk markers and limited associations with cognitive performance in this cohort of healthy older adults., Competing Interests: Conflict of interest The authors declare they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Ectopic lipid accumulation, including intra-pancreatic fat deposition (IPFD), exacerbates type 2 diabetes risk in susceptible individuals. Dysregulated circulating microRNAs (miRNAs) have been identified as correlating with clinical measures of pancreatitis, pancreatic cancer and type 1 diabetes. The aim of the current study was therefore to examine the association between circulating abundances of candidate miRNAs, IPFD and liver fat deposition as quantified using magnetic resonance imaging (MRI) and spectroscopy (MRS). Asian Chinese ( n = 34; BMI = 26.7 ± 4.2 kg/m 2 ) and European Caucasian ( n = 34; BMI = 28.0 ± 4.5 kg/m 2 ) females from the TOFI&#95;Asia cohort underwent MRI and MRS analysis of pancreas (MR-%IPFD) and liver fat (MR-%liver fat), respectively, to quantify ectopic lipid deposition. Plasma miRNA abundances of a subset of circulatory miRNAs associated with IPFD and liver fat deposition were quantified by qRT-PCR. miR-21-3p and miR-320a-5p correlated with MR-%IPFD, plasma insulin and HOMA2-IR, but not MR-%liver fat. MR-%IPFD remained associated with decreasing miR-21-3p abundance following multivariate regression analysis. miR-21-3p and miR-320a were demonstrated to be negatively correlated with MR-%IPFD, independent of ethnicity. For miR-21-3p, this relationship persists with the inclusion of MR-%liver fat in the model, suggesting the potential for a wider application as a specific circulatory correlate of IPFD.

Background: Metabolomic dysregulation following a meal in overweight individuals with the Metabolic Syndrome (MetS) involves multiple pathways of nutrient storage and oxidation., Objective: The aim of the current study was to perform an acute cross-over intervention to examine the interactive actions of meal glycaemic load (GL) on the dynamic responses of the plasma metabolome in overweight females., Methods: Postmenopausal women [63 ± 1.23y; Healthy (n = 20) and MetS (n = 20)] ingested two differing high-carbohydrate test meals (73 g carbohydrate; 51% energy) composed of either low glycemic index (LGI) or high (HGI) foods in a randomised sequence. Plasma metabolome was analysed using liquid chromatography-mass spectrometry (LC-MS)., Results: In the overweight women with MetS, there were suppressed postprandial responses for several amino acids (AAs), including phenylalanine, leucine, valine, and tryptophan, p < 0.05), irrespective of the meal type. Meal GL exerted a limited impact on the overall metabolomic response, although the postprandial levels of alanine were higher with the low GL meal and uric acid was greater following the high GL meal (p < 0.05)., Conclusions: MetS participants exhibited reduced differences in the concentrations of a small set of AAs and a limited group of metabolites implicated in energy metabolism following the meals. However, the manipulation of meal GL had minimal impact on the postprandial metabolome. This study suggests that the GL of a meal is not a major determinant of postprandial response, with a greater impact exerted by the metabolic health of the individual. Trial registration Australia New Zealand Clinical Trials Registry: ACTRN12615001108505 (21/10/2015)., (© 2023. The Author(s).)

Cold water immersion (CWI) following intense exercise is a common athletic recovery practice. However, CWI impacts muscle adaptations to exercise training, with attenuated muscle hypertrophy and increased angiogenesis. Tissue temperature modulates the abundance of specific miRNA species and thus CWI may affect muscle adaptations via modulating miRNA expression following a bout of exercise. The current study focused on the regulatory mechanisms involved in cleavage and nuclear export of mature miRNA, including DROSHA, EXPORTIN-5, and DICER. Muscle biopsies were obtained from the vastus lateralis of young males (n = 9) at rest and at 2, 4, and 48 h of recovery from an acute bout of resistance exercise, followed by either 10 min of active recovery (ACT) at ambient temperature or CWI at 10°C. The abundance of key miRNA species in the regulation of intracellular anabolic signaling (miR-1 and miR-133a) and angiogenesis (miR-15a and miR-126) were measured, along with several gene targets implicated in satellite cell dynamics (NCAM and PAX7) and angiogenesis (VEGF and SPRED-1). When compared to ACT, CWI suppressed mRNA expression of DROSHA (24 h p = 0.025 and 48 h p = 0.017), EXPORTIN-5 (24 h p = 0.008), and DICER (24 h p = 0.0034). Of the analyzed miRNA species, miR-133a (24 h p < 0.001 and 48 h p = 0.007) and miR-126 (24 h p < 0.001 and 48 h p < 0.001) remained elevated at 24 h post-exercise in the CWI trial only. Potential gene targets of these miRNA, however, did not differ between trials. CWI may therefore impact miRNA abundance in skeletal muscle, although the precise physiological relevance needs further investigation., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Understanding the genetic risk and mechanisms through which SARS-CoV-2 infection outcomes and comorbidities interact to impact acute and long-term sequelae is essential if we are to reduce the ongoing health burdens of the COVID-19 pandemic. Here we use a de novo protein diffusion network analysis coupled with tissue-specific gene regulatory networks, to examine putative mechanisms for associations between SARS-CoV-2 infection outcomes and comorbidities. Our approach identifies a shared genetic aetiology and molecular mechanisms for known and previously unknown comorbidities of SARS-CoV-2 infection outcomes. Additionally, genomic variants, genes and biological pathways that provide putative causal mechanisms connecting inherited risk factors for SARS-CoV-2 infection and coronary artery disease and Parkinson's disease are identified for the first time. Our findings provide an in depth understanding of genetic impacts on traits that collectively alter an individual's predisposition to acute and post-acute SARS-CoV-2 infection outcomes. The existence of complex inter-relationships between the comorbidities we identify raises the possibility of a much greater post-acute burden arising from SARS-CoV-2 infection if this genetic predisposition is realised., (© 2023. The Author(s).)

Background: Flexitarian, vegetarian and exclusively plant-based diets are increasingly popular, particularly amongst young adults. This is the first randomised dietary intervention to investigate the health, wellbeing, and behavioural implications of consuming a basal vegetarian diet that additionally includes low-to-moderate amounts of red meat (flexitarian) compared to one containing plant-based meat alternatives (PBMAs, vegetarian) in young adults (ClinicalTrials.gov NCT04869163). The objective for the current analysis is to measure adherence to the intervention, nutrition behaviours, and participants' experience with their allocated dietary group., Methods: Eighty healthy young adults participated in this 10-week dietary intervention as household pairs. Household pairs were randomised to receive either approximately three serves of red meat (average of 390 g cooked weight per individual, flexitarian group) or PBMAs (350-400 g per individual, vegetarian group) per week on top of a basal vegetarian diet. Participants were supported to adopt healthy eating behaviours, and this intervention was developed and implemented using a behaviour change framework. Adherence (eating allocated red meat or PBMA, abstaining from animal-based foods not provided by researchers) was continuously monitored, with total scores calculated at the end of the 10-week intervention period. Eating experiences were measured by the Positive Eating Scale and a purpose-designed exit survey, and a food frequency questionnaire measured dietary intake. Analyses used mixed effects modeling taking household clustering into account., Results: The total average adherence score was 91.5 (SD = 9.0) out of a possible 100, with participants in the flexitarian group scoring higher (96.1, SD = 4.6, compared to 86.7, SD = 10.0; p  < 0.001). Those receiving red meat were generally more satisfied with this allocation compared to those receiving the PBMAs, even though a leading motivation for participants joining the study was an opportunity to try plant-based eating (35% expressed that their interest in taking part was related to trying plant-based eating). Participants in both intervention groups had increased vegetable intake ( p  < 0.001), and reported more positive eating experiences ( p  = 0.020) and satisfaction with eating ( p  = 0.021) at the end of the 10-week intervention relative to baseline values., Conclusion: Methods to encourage engagement with the trial were successful, as participants demonstrated excellent adherence to the intervention. Observed differences in participants' adherence and experiences between flexitarian and vegetarian groups holds implications for the adoption of healthy, sustainable dietary patterns beyond this study alone., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gillies, Worthington, Li, Conner, Bermingham, Knowles, Cameron-Smith, Hannaford and Braakhuis.)

Background: β-cryptoxanthin is a dietary carotenoid for which there have been few studies on the safety and pharmacokinetics following daily oral supplementation., Methods: 90 healthy Asian women between 21 and 35 years were randomized into three groups: 3 and 6 mg/day oral β-cryptoxanthin, and placebo. At 2, 4, and 8 weeks of supplementation, plasma carotenoid levels were measured. The effects of β-cryptoxanthin on blood retinoid-dependent gene expression, mood, physical activity and sleep, metabolic parameters, and fecal microbial composition were investigated., Results: β-cryptoxanthin supplementation for 8 weeks (3 and 6 mg/day) was found to be safe and well tolerated. Plasma β-cryptoxanthin concentration was significantly higher in the 6 mg/day group (9.0 ± 4.1 µmol/L) compared to 3 mg/day group (6.0 ± 2.6 µmol/L) ( p < 0.03), and placebo (0.4 ± 0.1 µmol/L) ( p < 0.001) after 8 weeks. Plasma all-trans retinol, α-cryptoxanthin, α-carotene, β-carotene, lycopene, lutein, and zeaxanthin levels were not significantly changed. No effects were found on blood retinol-dependent gene expression, mood, physical activity and sleep, metabolic parameters, and fecal microbial composition., Conclusions: Oral β-cryptoxanthin supplementation over 8 weeks lead to high plasma concentrations of β-cryptoxanthin, with no impact on other carotenoids, and was well tolerated in healthy women.

Background: Maternal obesity during pregnancy is associated with an increased risk of obesity and metabolic disease in the offspring. Supplementation with fish oil (FO), which is insulin sensitizing, during pregnancy in mothers with overweight or obesity may prevent the development of greater adiposity and metabolic dysfunction in their children., Objectives: To determine the effects of FO supplementation throughout the second half of pregnancy and lactation in mothers with overweight or obesity on infant body composition and metabolism., Methods: A double-blind randomized controlled trial of 6 g FO (3.55 g/d of n-3 PUFAs) compared with olive oil (control) from mid-pregnancy until 3 mo postpartum. Eligible women had singleton pregnancies at 12-20 wk of gestation, and BMI ≥ 25 kg/m 2 . The primary outcome was the infant body fat percentage (DXA scans) at 2 wk of age. Secondary outcomes included maternal metabolic markers during pregnancy, infant anthropometry at 2 wk and 3 mo of age, and metabolic markers at 3 mo., Results: A total of 129 mothers were randomized, and 98 infants had a DXA scan at 2 wk., Primary Outcome: Imputed and nonimputed analyses showed no effects of FO supplementation on infant body fat percentage at age 2 wk., Secondary Outcomes: There were no treatment effects on infant outcomes at 2 wk, but FO infants had a higher BMI z-score (P = 0.025) and ponderal index (P = 0.017) at age 3 mo. FO supplementation lowered maternal triglycerides by 17% at 30 wk of pregnancy (P = 0.0002) and infant triglycerides by 21% at 3 mo of age (P = 0.016) but did not affect maternal or infant insulin resistance. The rate of emergency cesarean section was lower with FO supplementation [aRR = 0.38 (95%CI 0.16, 0.90); P = 0.027]., Conclusions: FO supplementation of mothers with overweight or obesity during pregnancy did not impact infant body composition. There is a need to follow up the offspring to determine whether the observed metabolic effects persist., Clinical Trial Registry Number: This study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617001078347p). In addition, the Universal Trial Number, WHO, was obtained (U1111-1199-5860)., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Evidence is accumulating that intake of animal-based and plant-based proteins has different effects on cardiometabolic health, but less is known about the health effect of isocaloric substitution of animal-based and plant-based proteins. Data from Asian populations are limited., Objectives: This study aimed to evaluate the effects of isocaloric substitution of total plant-based proteins for total and various animal-based protein food groups and to evaluate the effects of substituting protein from legumes and pulses for various animal-based protein food groups on cardiovascular disease (CVD) risk factors and predicted 10-y CVD risk., Methods: We conducted a cross-sectional analysis using data collected from 9211 Singapore residents (aged 21-75 y) from the Singapore Multi-Ethnic Cohort. Data on sociodemographic and lifestyle factors were collected using questionnaires. Dietary intakes were assessed using a validated FFQ. BMI, waist circumference, and blood pressure were measured during a physical examination, and blood samples were collected to measure lipid profiles. Associations were assessed by substitution models using a multiple linear regression analysis., Results: Isocaloric substitution of total plant-based proteins for total and all specific animal-based protein food groups were associated with lower BMI (β: -0.30; 95% CI: -0.38, -0.22), waist circumference (β: -0.85; 95% CI: -1.04, -0.66), and LDL cholesterol concentrations (β: -0.06; 95% CI: -0.08, -0.05) (P < 0.0056). Replacement of processed meat and processed seafood proteins with total plant-based proteins was associated with improvement in most CVD risk factors and predicted 10-y CVD risk. Replacement of oily fish with legume proteins was associated with lower HDL cholesterol and higher TG concentrations., Conclusions: The substitution of plant-based proteins for animal-based proteins, especially from processed meat and processed seafood, was inversely associated with the established CVD risk factors such as BMI, waist circumference, and lipid concentrations and predicted 10-y CVD risk. These findings warrant further investigation in independent studies in other Asian populations., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Purpose: B vitamins are required for the complex regulation of homocysteine and one-carbon (1C) metabolism. Nutritional supplements are frequently used by older adults to counter nutritional inadequacies. However, the postprandial use of B vitamins from supplements in 1C metabolism may be altered with age owing to impaired nutrient absorption and metabolic regulation. Despite implications for health and nutritional status, postprandial 1C metabolite responses have not been characterised in older adults., Methods: Healthy older (n = 20, 65-76 years) and younger (n = 20, 19-30 years) participants were recruited through online and printed advertisements in Auckland, New Zealand. Participants consumed a multivitamin and mineral supplement with a standard breakfast meal. Blood samples were collected at baseline and hourly for 4 h following ingestion. Plasma 1C metabolites (betaine, choline, cysteine, dimethylglycine, glycine, methionine, serine) were quantified using liquid chromatography coupled with mass spectrometry. Serum homocysteine, folate and vitamin B 12 were quantified on a Cobas e411 autoanalyzer., Results: Older adults had higher fasting homocysteine concentrations (older: 14.0 ± 2.9 µmol/L; younger: 12.2 ± 2.5 µmol/L; p = 0.036) despite higher folate (older: 36.7 ± 17.4 nmol/L; younger: 21.6 ± 7.6 nmol/L; p < 0.001) and similar vitamin B 12 concentrations (p = 0.143) to younger adults. However, a similar postprandial decline in homocysteine was found in older and younger subjects in response to the combined meal and supplement. Except for a faster decline of cystathionine in older adults (p = 0.003), the postprandial response of other 1C metabolites was similar between young and older adults., Conclusion: Healthy older adults appear to maintain postprandial responsiveness of 1C metabolism to younger adults, supported by a similar postprandial decline in homocysteine concentrations., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Human brain development starts in the embryonic period. Maternal preconception nutrition and nutrient availability to the embryo may influence brain development at this critical period following conception and early cellular differentiation, thereby affecting offspring neurodevelopmental and behavioural disorder risk. However, studying this is challenging due to difficulties in characterizing preconception nutritional status and few studies have objective neurodevelopmental imaging measures in children. We investigated the associations of maternal preconception circulating blood nutrient-related biomarker mixtures (~15 weeks before conception) with child behavioural symptoms (Child Behaviour Checklist (CBCL), aged 3 years) within the Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) study. The CBCL preschool form evaluates child behaviours based on syndrome scales and Diagnostic and Statistical Manual of Mental Disorders (DSM) oriented scales. These scales consist of internalizing problems, externalizing problems, anxiety problems, pervasive developmental problems, oppositional defiant, etc. We applied data-driven clustering and a method for modelling mixtures (Bayesian kernel machine regression, BKMR) to account for complex, non-linear dependencies between 67 biomarkers. We used effect decomposition analyses to explore the potential mediating role of neonatal (week 1) brain microstructure, specifically orientation dispersion indices (ODI) of 49 cortical and subcortical grey matter regions. We found that higher levels of a nutrient cluster including thiamine, thiamine monophosphate (TMP), pyridoxal phosphate, pyridoxic acid, and pyridoxal were associated with a higher CBCL score for internalizing problems (posterior inclusion probability (PIP) = 0.768). Specifically, thiamine independently influenced CBCL (Conditional PIP = 0.775). Higher maternal preconception thiamine level was also associated with a lower right subthalamic nucleus ODI (P-value = 0.01) while a lower right subthalamic nucleus ODI was associated with higher CBCL scores for multiple domains (P-value < 0.05). One potential mechanism is the suboptimal metabolism of free thiamine to active vitamin B1, but additional follow-up and replication studies in other cohorts are needed., (© 2023. The Author(s).)

Purpose: Mitochondrial dynamics are regulated by the differing molecular pathways variously governing biogenesis, fission, fusion, and mitophagy. Adaptations in mitochondrial morphology are central in driving the improvements in mitochondrial bioenergetics following exercise training. However, there is a limited understanding of mitochondrial dynamics in response to inactivity., Methods: Skeletal muscle biopsies were obtained from middle-aged males (n = 24, 49.4 ± 3.2 years) who underwent sequential 14-day interventions of unilateral leg immobilisation, ambulatory recovery, and resistance training. We quantified vastus lateralis gene and protein expression of key proteins involved in mitochondrial biogenesis, fusion, fission, and turnover in at baseline and following each intervention., Results: PGC1α mRNA decreased 40% following the immobilisation period, and was accompanied by a 56% reduction in MTFP1 mRNA, a factor involved in mitochondrial fission. Subtle mRNA decreases were also observed in TFAM (17%), DRP1 (15%), with contrasting increases in BNIP3L and PRKN following immobilisation. These changes in gene expression were not accompanied by changes in respective protein expression. Instead, we observed subtle decreases in NRF1 and MFN1 protein expression. Ambulatory recovery restored mRNA and protein expression to pre-intervention levels of all altered components, except for BNIP3L. Resistance training restored BNIP3L mRNA to pre-intervention levels, and further increased mRNA expression of OPA-1, MFN2, MTFP1, and PINK1 past baseline levels., Conclusion: In healthy middle-aged males, 2 weeks of immobilisation did not induce dramatic differences in markers of mitochondria fission and autophagy. Restoration of ambulatory physical activity following the immobilisation period restored altered gene expression patterns to pre-intervention levels, with little evidence of further adaptation to resistance exercise training., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Sheep milk (SM) is an alternate dairy source, which despite many similarities, has both compositional and structural differences in lipids compared to cow milk (CM). Studies are yet to examine the apparent digestibility of SM lipids, relative to CM, and the potential impact on the plasma lipidome., Objective: To determine the response of the circulatory lipidome to equal volume servings of SM and CM, in females who avoid dairy products., Method: In a double-blinded, randomized, cross-over trial, self-described dairy avoiding females ( n = 30; 24.4 ± 1.1 years) drank SM or CM (650 mL; 33.4 vs. 21.3 g total lipid content; reconstituted from spray dried milk powders) following an overnight fast. Blood samples were collected at fasting and at regular intervals over 4 h after milk consumption. The plasma lipidome was analyzed by LC-MS and fatty acids were quantified by GC-FID., Results: The overall postprandial triglyceride (TG) response was similar between SM and CM. TG concentrations were comparable at fasting for both groups, however they were higher after CM consumption at 30 min (interaction milk × time p = 0.003), well before any postprandial lipemic response. This was despite greater quantities provided by SM. However, there were notable differences in the postprandial fatty acid response, with SM leading to an increase in short- and medium-chain fatty acids (MCFAs) (C6:0, C8:0, and C10:0) and several long-chain fatty acids (LCFAs) (C18:1 t 11, c 9, t 11-CLA, and C20:0; interaction time × milk p < 0.05). This corresponded to a greater postprandial response for medium chain triglycerides (MCTs) C10:0, including TG(10:0/14:0/18:1), TG(16:0/10:0/12:0), and TG(16:0/10:0/14:0) (interaction time × milk p < 0.05)., Conclusions: Despite a higher fat content, SM ingestion resulted in a greater circulating abundance of MCTs, without increasing total postprandial triglyceride response, when compared to CM. The greater abundance and postprandial appearance of MCTs may provide advantageous metabolic responses in children and adults., Unique Identifier and Registry: U1111-1209-7768; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375324., Competing Interests: FT, LS, AM, MA, and LD were employed by AgResearch Ltd., Grasslands Research Center, Palmerston North, New Zealand. AS is employed by AgResearch Ltd., Lincoln Research Center, Lincoln, New Zealand. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Teng, Samuelsson, Milan, Subbaraj, Agnew, Shrestha, Cameron-Smith and Day.)

Background/objectives: Self-reported digestive intolerance to dairy foods is common. As dairy can be an important source of dietary protein, this study aimed to identify whether milk protein digestion is compromised in individuals with digestive intolerance., Subjects/methods: Adult women (n = 40) were enroled in this double-blinded, randomised cross-over trial, with digestive symptoms characterised using a lactose challenge and self-reported digestive symptom questionnaire. Participants were classified as either lactose intolerant (LI, n = 10), non-lactose dairy intolerant (NLDI, n = 20) or dairy tolerant (DT, n = 10). In a randomised sequence, participants consumed three different kinds of milk (750 ml); conventional milk (CON), a2 Milk™ (A2M), and lactose-free conventional milk (LF-CON). Circulatory plasma amino acid (AA) concentrations were measured at baseline and every 30 min until 3 h post-ingestion., Results: In all participants across all milk types, plasma AA concentrations (AUC 0-180 ) increased after milk ingestion with no significant differences in responses observed between milk types or participants (P > 0.05), with the exception of the suppressed lysine response in the DT group following A2M ingestion, relative to the other two groups and milk types (P < 0.05)., Conclusion: Milk protein digestion, as determined by circulatory AAs, is largely unaffected by dairy- and lactose- intolerances., (© 2022. The Author(s).)

Background: The tryptophan-kynurenine (KYN) pathway is linked to obesity-related systemic inflammation and metabolic health. The pathway generates multiple metabolites, with little available data on their relationships to early markers of increased metabolic disease risk in children. The aim of this study was to examine the association of multiple KYN pathway metabolites with metabolic risk markers in prepubertal Asian children., Methods: Fasting plasma concentrations of KYN pathway metabolites were measured using liquid chromatography-tandem mass spectrometry in 8-year-old children (n = 552) from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) prospective mother-offspring cohort study. The child's weight and height were used to ascertain overweight and obesity using local body mass index (BMI)-for-age percentile charts. Body fat percentage was measured by quantitative magnetic resonance. Abdominal circumference, systolic and diastolic blood pressure, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride, and HDL-cholesterol were used for the calculation of Metabolic syndrome scores (MetS). Serum triglyceride, BMI, gamma-glutamyl transferase (GGT), and abdominal circumference were used in the calculation of the Fatty liver index (FLI). Associations were examined using multivariable regression analyses., Results: In overweight or obese children (n = 93; 16.9% of the cohort), all KYN pathway metabolites were significantly increased, relative to normal weight children. KYN, kynurenic acid (KA), xanthurenic acid (XA), hydroxyanthranilic acid (HAA) and quinolinic acid (QA) all showed significant positive associations with body fat percentage (B(95% CI) = 0.32 (0.22,0.42) for QA), HOMA-IR (B(95% CI) = 0.25 (0.16,0.34) for QA), and systolic blood pressure (B(95% CI) = 0.14(0.06,0.22) for QA). All KYN metabolites except 3-hydroxykynurenine (HK) significantly correlated with MetS (B (95% CI) = 0.29 (0.21,0.37) for QA), and FLI (B (95% CI) = 0.30 (0.21,0.39) for QA)., Conclusions: Higher plasma concentrations of KYN pathway metabolites are associated with obesity and with increased risk for metabolic syndrome and fatty liver in prepubertal Asian children., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Context: The kynurenine pathway generates metabolites integral to energy metabolism, neurotransmission, and immune function. Circulating kynurenine metabolites positively correlate with adiposity in children and adults, yet it is not known whether this relationship is present already at birth., Objective: In this prospective longitudinal study, we investigate the relationship between cord blood kynurenine metabolites and measures of adiposity from birth to 4.5 years., Methods: Liquid chromatography-tandem mass spectrometry was used to quantify cord blood kynurenine metabolites in 812 neonates from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. Fat percentage was measured by air displacement plethysmography and abdominal adipose tissue compartment volumes; superficial (sSAT) and deep subcutaneous (dSAT) and internal adipose tissue were quantified by magnetic resonance imaging at early infancy in a smaller subset of neonates, and again at 4 to 4.5 years of age., Results: Cord blood kynurenine metabolites appeared to be higher in female newborns, higher in Indian newborns compared with Chinese newborns, and higher in infants born by cesarean section compared with vaginal delivery. Kynurenine, xanthurenic acid, and quinolinic acid were positively associated with birthweight, but not with subsequent weight during infancy and childhood. Quinolinic acid was positively associated with sSAT at birth. Kynurenic acid and quinolinic acid were positively associated with fat percentage at 4 years., Conclusion: Several cord blood kynurenine metabolite concentrations were positively associated with birthweight, with higher kynurenic acid and quinolinic acid correlating to higher percentage body fat in childhood, suggesting these cord blood metabolites as biomarkers of early childhood adiposity., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Red meat is a nutrient-dense food and a dietary staple. A new generation of plant-based meat analogs (PBMAs) have been designed to mimic the experience of eating meat, but there is limited evidence about their digestive efficacy and nutritional quality., Objectives: We compared the postprandial digestive response of a single meal containing meat commercially raised in New Zealand, including lamb, on-farm pasture-raised beef (Pasture), or grain-finished beef (Grain) with a PBMA (Beyond Burger; Beyond Meat) sold through consumer retail. The primary outcome was the appearance of amino acids in plasma. Secondary outcomes included glucose and insulin, appetite assessment, and anthropometry., Methods: Thirty healthy men (20-34 y) participated in a double-blinded randomized crossover trial. Each consumed 1 of the 4 test meals on 4 occasions separated by a washout period of at least 1 wk, following an overnight fast. The meal was a burrito-style wrap containing meat or PBMAs, vegetables, salsa, and seasonings in a flour tortilla. The amount of Pasture, Grain, Lamb, or BB was 220 g raw (∼160 g cooked). Venous blood samples were collected over 4 h. Appetite and hunger status was scored with visual analog scales., Results: Pre-meal amino acid concentrations in plasma did not differ by group ( P  > 0.9), although several nonessential amino acids differed strongly according to participant BMI. Postprandial amino acids peaked at 2-3 h in all groups. The BB meal produced significantly lower plasma concentrations of total, essential, branched-chain, and non-proteogenic amino acids than the Lamb, Pasture, or Grain meals, based on AUC. There were no significant differences between meal groups in scores for hunger, fullness, or cravings., Conclusions: Red meat meals exhibited greater bioavailability of amino acids compared with the PBMA (BB). Pasture versus Grain origins of the beef had little influence on participants' responses. This trial was registered at ClinicalTrials.gov as NCT04545398., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Purpose: Cardiovascular diseases and cognitive decline, predominant in ageing populations, share common features of dysregulated one-carbon (1C) and cardiometabolic homeostasis. However, few studies have addressed the impact of multifaceted lifestyle interventions in older adults that combine both nutritional supplementation and resistance training on the co-regulation of 1C metabolites and cardiometabolic markers., Methods: 95 institutionalised older adults (83 ± 6 years, 88.4% female) were randomised to receive resistance training with or without nutritional supplementation (Fortifit), or cognitive training (control for socialisation) for 6 months. Fasting plasma 1C metabolite concentrations, analysed by liquid chromatography coupled with mass spectrometry, and cardiometabolic parameters were measured at baseline and the 3- and 6-month follow-ups., Results: Regardless of the intervention group, choline was elevated after 3 months, while cysteine and methionine remained elevated after 6 months (mixed model time effects, p < 0.05). Elevated dimethylglycine and lower betaine concentrations were correlated with an unfavourable cardiometabolic profile at baseline (spearman correlations, p < 0.05). However, increasing choline and dimethylglycine concentrations were associated with improvements in lipid metabolism in those receiving supplementation (regression model interaction, p < 0.05)., Conclusion: Choline metabolites, including choline, betaine and dimethylglycine, were central to the co-regulation of 1C metabolism and cardiometabolic health in older adults. Metabolites that indicate upregulated betaine-dependent homocysteine remethylation were elevated in those with the greatest cardiometabolic risk at baseline, but associated with improvements in lipid parameters following resistance training with nutritional supplementation. The relevance of how 1C metabolite status might be optimised to protect against cardiometabolic dysregulation requires further attention., (© 2021. The Author(s).)

This study aimed to identify biomarkers of appetite response, modelled using a dose-rising whey protein preload intervention. Female participants (n = 24) with body mass index (BMI) between 23 and 40 kg/m 2 consumed preload beverages (0 g protein water control, WC; 12.5 g low-dose protein, LP; or 50.0 g high-dose protein, HP) after an overnight fast, in a randomised cross over design. Repeated venous blood samples were collected to measure plasma biomarkers of appetite response, including glucose, glucoregulatory peptides, gut peptides, and amino acids (AAs). Appetite was assessed using Visual Analogue Scales (VAS) and ad libitum energy intake (EI). Dose-rising protein beverage significantly changed the postprandial trajectory of almost all biomarkers (treatment*time, p < 0.05), but did not suppress postprandial appetite (treatment*time, p > 0.05) or EI (ANOVA, p = 0.799). Circulating glycine had the strongest association with appetite response. Higher area under the curve (AUC 0-240 ) glycine was associated with lower EI (p = 0.026, trend). Furthermore, circulating glycine was associated with decreased Hunger in all treatment groups, whereas the associations of glucose, alanine and amylin with appetite were dependent on treatment groups. Multivariate models, incorporating multiple biomarkers, improved the estimation of appetite response (marginal R 2 , range: 0.13-0.43). In conclusion, whilst glycine, both alone and within a multivariate model, can estimate appetite response to both water and whey protein beverage consumption, a large proportion of variance in appetite response remains unexplained. Most biomarkers, when assessed in isolation, are poor predictors of appetite response, and likely of utility only in combination with VAS and EI., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The trend of flexitarian eating patterns is on the rise, with young adults among the biggest adopters claiming health and environmental reasons to reduce red meat intake. Nutrient-dense meat and animal products are often the lynchpin of these diets, even when consumed only occasionally and in moderate amounts. Red meat provides forms and concentrations of essential proteins, lipids, and micronutrients that are scarce in exclusively vegetarian regimens., Objective: The aim of this study is to consider the effects of moderate consumption of lean red meat as part of an otherwise vegetarian balanced diet and its impact on biomarkers of sustained health and well-being., Methods: A cohort of healthy, young (20-34 years old, n=80) male and female participants will take part in a 2-arm, parallel randomized controlled trial (RCT) for a duration of 12 weeks, with a 3-month posttrial follow-up. The trial will commence with a 2-week assessment period followed by allocation to the intervention arms. The intervention will include the consumption of red meat or meat alternatives 3 times per week for 10 weeks. Blood samples of the participants will be collected to measure changes in erythrocyte fatty acid distribution, circulating amino acids, neurotransmitters, markers of mineral status, and inflammatory markers. Questionnaires to assess well-being and mental health will be undertaken every 2 weeks. Body composition, physical function, and blood parameters will be assessed at allocation (t 0 ), week 5 into the intervention (t 5 ), and post intervention (t 10 )., Results: The protocol has been developed using the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) checklist and the outcomes will be reported in accordance with the CONSORT (Consolidated Standards of Reporting Trials) guidelines. The trial was approved by the New Zealand Ministry of Health's Health and Disability Ethics Committees (protocol 20/STH/157). The results of this study will be communicated via publication., Conclusions: To our knowledge, this is the first RCT investigating the overarching health consequences of consuming pasture-fed red meat or no meat as part of a healthy diet., Trial Registration: ClinicalTrials.gov NCT04869163; https://clinicaltrials.gov/ct2/show/NCT04869163., International Registered Report Identifier (irrid): PRR1-10.2196/30909., (©Andrea Braakhuis, Nicola Gillies, Anna Worthington, Scott Knowles, Tamlin Conner, Rajshri Roy, Toan Pham, Emma Bermingham, David Cameron-Smith. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 21.12.2021.)

Central fat accumulation is a significant determinant of cardio-metabolic health risk, known to differ between ethnically distinct human populations. Despite evidence for preferential central adiposity in Asian populations, the proportional distribution between the subcutaneous and visceral compartments in Chinese postmenopausal women has not been thoroughly investigated. For this analysis, volumetrically quantified subcutaneous and visceral adipose tissue (SAT, VAT) in the pelvic and abdominal regions of postmenopausal Asian (Chinese-Singaporean) and Caucasian (German) women matched for age and Body Mass Index (BMI) was undertaken, to examine such differences between the two groups. Volumes were calculated from segmentations of magnetic resonance imaging datasets of the abdomen and pelvis. Despite SAT, VAT, and the corresponding total adipose tissue (TAT) being similar between the groups, VAT/SAT and VAT/TAT were higher in the Asian group (by 24.5% and 18.2%, respectively, each p = 0.02). Further, VAT/SAT and VAT/TAT were positively correlated with BMI in the Caucasian group only ( p = 0.02 and p = 0.01, respectively). We concluded that VAT is proportionally higher in the non-obese Asian women, compared to the Caucasian women of matched age and BMI. This conclusion is in agreement with existing literature showing higher abdominal adiposity in Asian populations. Additionally, in the Asian group, BMI did not correlate with visceral adiposity on a significant level. Further analysis is required to examine the extent to which this increased VAT may impact cardio-metabolic health. There is, however, a need to emphasize healthy lifestyle behaviors in non-obese post-menopausal women of Chinese ancestry.

A high protein intake at old age is important for muscle protein synthesis, however, this could also trigger protein oxidation with the potential risk for DNA damage. The aim of this study was to investigate whether an increased protein intake at recommended level or well above would affect DNA damage or change levels of reduced (GSH) and oxidised glutathione (GSSG) in community-dwelling elderly subjects. These analyses were performed in two randomized intervention studies, in Austria and in New Zealand. In both randomized control trials, the mean protein intake was increased with whole foods, in the New Zealand study ( n = 29 males, 74.2 ± 3.6 years) to 1.7 g/kg body weight/d (10 weeks intervention; p < 0.001)) in the Austrian study ( n = 119 males and females, 72.9 ± 4.8 years) to 1.54 g/kg body weight/d (6 weeks intervention; p < 0.001)). In both studies, single and double strand breaks and as formamidopyrimidine-DNA glycosylase-sensitive sites were investigated in peripheral blood mononuclear cells or whole blood. Further, resistance to H 2 O 2 induced DNA damage, GSH, GSSG and CRP were measured. Increased dietary protein intake did not impact on DNA damage markers and GSH/GSSG levels. A seasonal-based time effect ( p < 0.05), which led to a decrease in DNA damage and GSH was observed in the Austrian study. Therefore, increasing the protein intake to more than 20% of the total energy intake in community-dwelling seniors in Austria and New Zealand did not increase measures of DNA damage, change glutathione status or elevate plasma CRP.

Objectives: Dietary strategies to promote successful aging are divergent. Higher-protein diets are recommended to preserve skeletal muscle mass and physical function. Conversely, increased B-vitamin intake, supporting one-carbon (1C) metabolism, reduces the risk of cognitive decline and cardiovascular disease. On the hypothesis that higher protein intake through animal-based sources will benefit 1C regulation by the supply of B vitamins (folate, riboflavin, and vitamins B 6 and B 12 ) and methyl donors (choline) despite higher methionine intake, this study explored the effect of a higher-protein diet on 1C metabolite status in older men compared to current protein recommendations., Methods: Older men (age, 74 ± 3 y) were randomized to receive a diet for 10 wk containing either the recommended dietary allowance (RDA) of protein (0.8 g/kg body weight/d, n = 14), or double that amount (2RDA, n = 15), with differences in protein accounted for by modifying carbohydrate intake. Intervention diets were matched to each individual's energy requirements based on the Harris-Benedict equation and adjusted fortnightly as required depending on physical activity and satiety. Fasting plasma 1C metabolite concentrations were quantified by liquid chromatography coupled with mass spectrometry at baseline and after 10 wk of intervention., Results: Plasma homocysteine concentrations were reduced from baseline to follow-up with both diets. Changes in metabolite ratios reflective of betaine-dependent homocysteine remethylation were specific to the RDA diet, with an increase in the betaine-to-choline ratio and a decrease in the dimethylglycine-to-betaine ratio. Comparatively, increasing folate intake was positively associated with a change in choline concentration and inversely with the betaine-to-choline ratio for the 2RDA group., Conclusions: Adding to the known benefits of higher protein intake in older people, this study supports a reduction of homocysteine with increased consumption of animal-based protein, although the health effects of differential response of choline metabolites to a higher-protein diet remain uncertain., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Myocellular stress with high-frequency blood flow-restricted resistance exercise (BFRRE) was investigated by measures of heat shock protein (HSP) responses, glycogen content, and inflammatory markers. Thirteen participants [age: 24 ± 2 yr (means ± SD), 9 males] completed two 5-day blocks of seven BFRRE sessions, separated by 10 days. Four sets of unilateral knee extensions to failure at 20% of one-repetition maximum (1RM) were performed. Muscle samples obtained before, 1 h after the first session in the first and second block ( acute 1 and acute 2 ), after three sessions ( day 4 ), during the "rest week," and at 3 ( post 3 ) and 10 days postintervention ( post 10 ) were analyzed for HSP70, αB-crystallin, glycogen [periodic acid-Schiff (PAS) staining], mRNAs, miRNAs, and CD68 + (macrophages) and CD66b + (neutrophils) cell numbers. αB-crystallin translocated from the cytosolic to the cytoskeletal fraction after acute 1 and acute 2 ( P < 0.05) and immunostaining revealed larger responses in type I than in type II fibers ( acute 1 , 225 ± 184% vs. 92 ± 81%, respectively, P = 0.001). HSP70 was increased in the cytoskeletal fraction at day 4 and post 3 , and immunostaining intensities were more elevated in type I than in type II fibers at day 4 (206 ± 84% vs. 72 ± 112%, respectively, P <0.001), during the rest week (98 ± 66% vs. 42 ± 79%, P < 0.001), and at post 3 (115 ± 82% vs. 28 ± 78%, P = 0.003). Glycogen content was reduced in both fiber types, but most pronounced in type I, which did not recover until the rest week (-15% to 29%, P ≤ 0.001). Intramuscular macrophage numbers were increased by ∼65% postintervention, but no changes were observed in muscle neutrophils. We conclude that high-frequency BFRRE with sets performed till failure stresses both fiber types, with type I fibers being most affected. NEW & NOTEWORTHY BFRRE has been reported to preferentially stress type I muscle fibers, as evidenced by HSP responses. We extend these findings by showing that the HSP responses occur in both fiber types but more so in type I fibers and that they can still be induced after a short-term training period. Furthermore, the reductions in glycogen content of type I fibers after strenuous frequent BFRRE in unaccustomed subjects can be prolonged (≥5 days), probably due to microdamage.

Obesity is a growing health problem worldwide. The renin-angiotensin system (RAS) is present in adipose tissue, and evidence suggests that it is involved in both diet-induced obesity and the inflammation associated with obesity. The present experiments determined the effect of (1) different angiotensin-converting enzyme (ACE) inhibitors (captopril, perindopril, enalapril) and angiotensin receptor blockers (ARBs: telmisartan, losartan) on adiposity of mice fed a high-fat diet for 28 days (2); acute treatment with the ACE-inhibitor captopril on gene expression of inflammatory markers in mice fed a high-fat diet (HFD); and (3) short-term (2 days) and chronic (28 days) treatment of ACE-inhibition on energy expenditure (EE) and energy balance in mice fed HFD ad libitum (AL), as well as receiving HFD limited to the amount of calories eaten by controls (pair-fed (PF) group). Body weight, food intake, adiposity and plasma leptin were lower in ACE inhibitor or ARB-treated groups over 28 days compared with HFD untreated mice. Short-term treatment with captopril led to increased EE relative to the level in the PF group. After 28 days, EE was lower in both captopril-treated and PF mice compared with AL, but the effect was greater in the captopril-treated group. Adiponectin was elevated in captopril-treated mice, but not in PF mice, after both 2 and 28 days. Additionally, acute RAS blockade in HFD-fed mice reduced mRNA expression for MCP-1, IL-6, TLR4, and leptin in adipose tissue relative to values in untreated groups. These data demonstrate that ACE inhibition and angiotensin receptor blockade reduce food intake to produce weight loss and suggest that the anti-inflammatory effects of ACE inhibition may be independent of weight loss., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mitchell, Premaratna, Bennett, Lambrou, Stahl, Jois, Barber, Antoniadis, Woods, Cameron-Smith, Weisinger and Begg.)

Background: Differing environmental conditions experienced by mother-infant dyads may influence composition of the milk received by the infant. As a consequence, diverse milk compositional profiles may contribute to different postnatal outcomes, especially in infants facing adverse perinatal environments. We investigated whether variability in milk concentrations of key metabolic hormones is associated with different growth outcomes in infants born preterm, a perinatal complication known to impact on infant growth. Methods: Human milk samples were collected from 169 mothers of 191 infants enrolled in the DIAMOND trial, a randomized trial of nutrition for moderate-late preterm infants, at 5 and 10 days postpartum and again at 4 months' corrected age and analyzed for leptin, adiponectin and insulin-like growth factor (IGF)-1. Infant weight and body composition were measured at birth, discharge and 4 months' corrected age. Multiple linear regression models were used to examine correlations between milk hormone concentrations, weight z-scores and body composition at discharge and 4 months' corrected age, and weight gain from birth to 4 months' corrected age. Sex-specific interactions were examined. Results: Higher milk IGF-1 concentrations on day 5 after birth were associated with greater infant fat-free mass at 4 months' corrected age. Milk IGF-1 concentrations at 4 months were positively associated with fat mass and fat-free mass at 4 months in boys but not girls. Milk leptin concentrations on day 5 after birth were positively associated with fat mass at discharge from hospital, but negatively associated with fat mass at 4 months' corrected age. No significant association was found for milk adiponectin concentrations. Conclusion: Milk IGF-1 and leptin concentrations in mothers of moderate-late preterm babies are associated with different growth and body composition through to 4 months' corrected age and these associations are often different in boys and girls. The sex-specific effects of nutrient and hormone exposure during early life in preterm infants warrants further investigation to optimize the nutritional care these infants receive, particularly in hospital, where the same nutrition is provided to boys and girls., Competing Interests: AM was employed by the company AgResearch Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Galante, Reynolds, Milan, Alexander, Bloomfield, Jiang, Asadi, Muelbert, Cameron-Smith, Pundir, Vickers and the DIAMOND study team.)

Background: Infants born moderate to late preterm constitute the majority of preterm births, yet guidelines for their nutritional care are unclear. Maternal milk is the most appropriate nutrition for these infants; however, its composition can be influenced by environmental factors. The present study therefore investigated perinatal predictors of human milk composition in a preterm cohort., Methods: Milk was collected during the DIAMOND trial (DIfferent Approaches to Moderate and late preterm Nutrition: Determinants of feed tolerance, body composition and development) from 169 mothers of 191 infants at three time-points (5 and 10 days post partum and 4 months' corrected age). Leptin, adiponectin and insulin-like growth factor-1 (IGF-1) were analysed by enzyme-linked immunosorbent assay. Generalised mixed models were used to evaluate associations between milk composition and maternal/infant/perinatal factors., Results: Most findings were independent of collection time-point. Gestational diabetes was associated with lower adiponectin. Higher adiponectin and lower leptin were associated with higher socioeconomic status, higher maternal education and ability to fully breastfeed at discharge from hospital. Higher leptin was associated with high perceived stress during hospital admission. Milk IGF-1 displayed sex-specific patterns in association with maternal social deprivation., Conclusion: Maternal, infant and environmental factors during the perinatal period were associated with milk compositional profiles throughout lactation. Further clinical trials should investigate the impact of such changes in terms of long-term infant outcomes., Impact: Human milk is the best nutrition for the infant. However, its composition may be susceptible to alterations determined by pathological conditions mother and infant may face throughout pregnancy and in the perinatal period. This study found that perinatal factors are associated with human milk composition from early to late lactation. If human milk composition throughout lactation is "programmed" during pregnancy or early lactation, infants who were exposed in utero to environmental insults may still be exposed to them during lactation. The impact of human milk compositional alteration on infant growth following perinatal pathological events requires further investigation.

Background: The potential of a ketone monoester (β-hydroxybutyrate; KEβHB) supplement to rapidly mimic a state of nutritional ketosis offers a new therapeutic possibility for diabetes prevention and management. While KEβHB supplementation has a glucose-lowering effect in adults with obesity, its impact on glucose control in other insulin-resistant states is unknown., Objectives: The primary objective was to investigate the effect of KEβHB-supplemented drink on plasma glucose in adults with prediabetes. The secondary objective was to determine its impact on plasma glucoregulatory peptides., Methods: This randomized controlled trial [called CETUS (Cross-over randomizEd Trial of β-hydroxybUtyrate in prediabeteS)] included 18 adults [67% men, mean age = 55 y, mean BMI (kg/m2) = 28.4] with prediabetes (glycated hemoglobin between 5.7% and 6.4% and/or fasting plasma glucose between 100 and 125 mg/dL). Participants were randomly assigned to receive KEβHB-supplemented and placebo drinks in a crossover sequence (washout period of 7-10 d between the drinks). Blood samples were collected from 0 to 150 min, at intervals of 30 min. Paired-samples t tests were used to investigate the change in the outcome variables [β-hydroxybutyrate (βHB), glucose, and glucoregulatory peptides] after both drinks. Repeated measures analyses were conducted to determine the change in concentrations of the prespecified outcomes over time., Results: Blood βHB concentrations increased to 3.5 mmol/L within 30 minutes after KEβHB supplementation. Plasma glucose AUC was significantly lower after KEβHB supplementation than after the placebo [mean difference (95% CI): -59 (-85.3, -32.3) mmol/L × min]. Compared with the placebo, KEβHB supplementation led to significantly greater AUCs for plasma insulin [0.237 (0.044, 0.429) nmol/L × min], C-peptide [0.259 (0.114, 0.403) nmol/L × min], and glucose-dependent insulinotropic peptide [0.243 (0.085, 0.401) nmol/L × min], with no significant differences in the AUCs for amylin, glucagon, and glucagon-like peptide 1., Conclusions: Ingestion of the KEβHB-supplemented drink acutely increased the blood βHB concentrations and lowered the plasma glucose concentrations in adults with prediabetes. Further research is needed to investigate the dynamics of repeated ingestions of a KEβHB supplement by individuals with prediabetes, with a view to preventing new-onset diabetes. This trial was registered at www.clinicaltrials.gov as NCT03889210., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The prevalence of childhood obesity is increasing worldwide, and the children of women who are obese during pregnancy are at greatest risk. This risk may be mediated by exaggeration of the normal insulin resistance of pregnancy. Omega-3 (n-3) fats are insulin sensitizing. Supplementation during pregnancy may reduce metabolic risk and adiposity in the children. Though results from animal studies are encouraging, completed clinical trials have not demonstrated this benefit. However, to our knowledge, previous studies have not targeted women who are overweight or obese while pregnant-the group at greatest risk for insulin resistance and most likely to benefit from n-3. In this narrative review, the importance of performing clinical trials restricted to women who are overweight or obese is discussed, as is the potential importance of n-3 dose, oil source and quality, and the timing of the intervention., (© The Author(s) 2020. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Disuse-induced muscle atrophy is accompanied by a blunted postprandial response of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Conflicting observations exist as to whether postabsorptive mTORC1 pathway activation is also blunted by disuse and plays a role in atrophy. It is unknown whether changes in habitual protein intake alter mTORC1 regulatory proteins and how they may contribute to the development of anabolic resistance. The primary objective of this study was to characterize the downstream responsiveness of skeletal muscle mTORC1 activation and its upstream regulatory factors, following 14 days of lower limb disuse in middle-aged men (45-60 yr). The participants were further randomized to receive daily supplementation of 20 g/d of protein ( n = 12; milk protein concentrate) or isocaloric carbohydrate placebo ( n = 13). Immobilization reduced postabsorptive skeletal muscle phosphorylation of the mTORC1 downstream targets, 4E-BP1, P70S6K, and ribosomal protein S6 (RPS6), with phosphorylation of the latter two decreasing to a greater extent in the placebo, compared with the protein supplementation groups (37% ± 13% vs. 14% ± 11% and 38% ± 20% vs. 25% ± 8%, respectively). Sestrin2 protein was also downregulated following immobilization irrespective of supplement group, despite a corresponding increase in its mRNA content. This decrease in Sestrin2 protein was negatively correlated with the immobilization-induced change in the in silico-predicted regulator miR-23b-3p. No other measured upstream proteins were altered by immobilization or supplementation. Immobilization downregulated postabsorptive mTORC1 pathway activation, and 20 g/day of protein supplementation attenuated the decrease in phosphorylation of targets regulating muscle protein synthesis.

Scope: B vitamers are co-enzymes involved in key physiological processes including energy production, one-carbon, and macronutrient metabolism. Studies profiling B vitamers simultaneously in parent-child dyads are scarce. Profiling B vitamers in parent-child dyads enables an insightful determination of gene-environment contributions to their circulating concentrations. We aimed to characterise: (a) parent-child dyad concordance, (b) generation (children versus adults), (c) age (within the adult subgroup (age range 28-71 years)) and (d) sex differences in plasma B vitamer concentrations in the CheckPoint study of Australian children., Methods and Results: 1166 children (11 ± 0.5 years, 51% female) and 1324 parents (44 ± 5.1 years, 87% female) took part in a biomedical assessment of a population-derived longitudinal cohort study: The Growing Up in Australia's Child Health CheckPoint. B vitamer levels were quantified by UHPLC/MS-MS. B vitamer levels were weakly concordant between parent-child pairs (10-31% of variability explained). All B vitamer concentrations exhibited generation-specificity, except for flavin mononucleotide (FMN). The levels of thiamine, pantothenic acid, and 4-pyridoxic acid were higher in male children, and those of pantothenic acid were higher in male adults compared to their female counterparts., Conclusion: Family, age, and sex contribute to variations in the concentrations of plasma B vitamers in Australian children and adults.

Purpose of Review: Docosapentaenoic acid (DPA) is a minor omega-3 fatty acid (FA) which has been frequently overlooked in lipid research. This review examines the biochemical and physiological outcomes of human trials which have used pure preparations of DPA (n - 3 DPA) and also recent developments in specialized proresolving lipid mediators (SPMs) derived from n - 3 DPA., Recent Findings: There have been only been two human studies and eleven animal studies with pure n - 3 DPA. The doses of n - 3 DPA used in the human trials have been 1-2 g/day. n - 3 DPA abundance is increased in blood lipid fractions within 3-4 days of supplementation. n - 3 DPA has the potential for unique properties, with a greater similarity in biological functioning with docosahexaenoic acid (DHA), than eicosapentaenoic acid (EPA). Despite the typically low levels of n - 3 DPA in most tissue lipids relative to EPA and DHA, unique SPMs, such as resolvins, maresins and protectins of the n - 3 DPA type, are involved in resolution of inflammation and regulating immune function., Summary: We suggest that measurement of blood levels of n - 3 DPA gives no indication of its broad biological roles, but that the true functionality of this enigmatic n - 3 polyunsaturated fatty acid (PUFA) remains obscure until more is known about the properties of the unique DPA-derived SPMs., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Excessive adipose tissue is central to disease burden posed by the Metabolic Syndrome (MetS). Whilst much is known of the altered transcriptomic regulation of adipose tissue under fasting conditions, little is known of the responses to high-fat meals., Methods: Nineteen middle-aged males (mean ± SD 52.0 ± 4.6 years), consumed two isocaloric high-fat, predominately dairy-based or soy-based, breakfast meals. Abdominal subcutaneous adipose biopsies were collected after overnight fast (0 h) and 4 h following each meal. Global gene expression profiling was performed by microarray (Illumina Human WG-6 v3)., Results: In the fasted state, 13 genes were differently expressed between control and MetS adipose tissue (≥1.2 fold-difference, p < 0.05). In response to the meals, the control participants had widespread increases in genes related to cellular nutrient responses (≥1.2 fold-change, p < 0.05; 2444 & 2367 genes; dairy & soy, respectively). There was blunted response in the MetS group (≥1.2 fold-change, p < 0.05; 332 & 336 genes; dairy & soy, respectively)., Conclusions: In middle-aged males with MetS, a widespread suppression of the subcutaneous adipose tissue nutrient responsive gene expression suggests an inflexibility in the transcriptomic responsiveness to both high-fat meals., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Sheep milk (SM) is a possible alternate dairy source for those who experience digestive symptoms with cow milk (CM). While both the milks contain lactose, one of the causes for self-reported intolerance to CM, the composition of SM and CM also differs across proteins and fats, which have been shown to impact digestive processes. Objective: To compare the acute digestive comfort and lactose malabsorption of SM to CM in female dairy avoiders. Method: In a double-blinded, randomized cross over trial, 30 dairy-avoiding females (aged 20-30 years) drank 650 mL of SM or CM (each reconstituted from spray dried powder) following an overnight fast, on two separate occasions at least 1 week apart. Blood samples were collected for glucose and insulin assessment, and single nucleotide polymorphisms of the lactase ( LCT ) gene (C/T 13910 and G/A 22018 ). Breath H 2 and visual analog scale (VAS) digestive symptom scores were recorded at fasting and regular intervals over 4 h after ingestion. Results: Eighty percentage of study participants were lactase non-persistent (LNP; CC 13910 and GG 22018 genotype). Digestive symptoms, including abdominal cramps, distension, rumbling, bloating, belching, diarrhea, flatulence, vomiting, and nausea, were similar in response to SM and CM ingestion (milk × time, P > 0.05). Breath H 2 was greater after CM than SM (72 ± 10 vs. 43 ± 6 ppm at 240 min, P < 0.001), which may be due to greater lactose content in CM (33 vs. 25 g). Accordingly, when corrected for the lactose content breath H 2 did not differ between the two milks. The response remained similar when analyzed in the LNP subset alone ( n = 20). Conclusions: Despite a higher energy and nutrient content, SM did not increase adverse digestive symptoms after ingestion, relative to CM, although there was a reduced breath H 2 response, which could be attributed to the lower lactose content in SM. The tolerability of SM should be explored in populations without lactose intolerance for whom underlying trigger for intolerance is unknown., Competing Interests: AM, LS, and LD are current employees of AgResearch Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shrestha, Samuelsson, Sharma, Day, Cameron-Smith and Milan.)

Background: Translational capacity (i.e. ribosomal mass) is a key determinant of protein synthesis and has been associated with skeletal muscle hypertrophy. The role of translational capacity in muscle atrophy and regrowth from disuse is largely unknown. Therefore, we investigated the effect of muscle disuse and reloading on translational capacity in middle-aged men (Study 1) and in rats (Study 2)., Methods: In Study 1, 28 male participants (age 50.03 ± 3.54 years) underwent 2 weeks of knee immobilization followed by 2 weeks of ambulatory recovery and a further 2 weeks of resistance training. Muscle biopsies were obtained for measurement of total RNA and pre-ribosomal (r)RNA expression, and vastus lateralis cross-sectional area (CSA) was determined via peripheral quantitative computed tomography. In Study 2, male rats underwent hindlimb suspension (HS) for either 24 h (HS 24 h, n = 4) or 7 days (HS 7d, n = 5), HS for 7 days followed by 7 days of reloading (Rel, n = 5) or remained as ambulatory weight bearing (WB, n = 5) controls. Rats received deuterium oxide throughout the study to determine RNA synthesis and degradation, and mTORC1 signalling pathway was assessed., Results: Two weeks of immobilization reduced total RNA concentration (20%) and CSA (4%) in men (both P ≤ 0.05). Ambulatory recovery restored total RNA concentration to baseline levels and partially restored muscle CSA. Total RNA concentration and 47S pre-rRNA expression increased above basal levels after resistance training (P ≤ 0.05). In rats, RNA synthesis was 30% lower while degradation was ~400% higher in HS 7d in soleus and plantaris muscles compared with WB (P ≤ 0.05). mTORC1 signalling was lower in HS compared with WB as was 47S pre-rRNA (P ≤ 0.05). With reloading, the aforementioned parameters were restored to WB levels while RNA degradation was suppressed (P ≤ 0.05)., Conclusions: Changes in RNA concentration following muscle disuse and reloading were associated with changes in ribosome biogenesis and degradation, indicating that both processes are important determinants of translational capacity. The pre-clinical data help explain the reduced translational capacity after muscle immobilization in humans and demonstrate that ribosome biogenesis and degradation might be valuable therapeutic targets to maintain muscle mass during disuse., (© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Healthy aging can be promoted by enhanced metabolic fitness and physical capacity. Mitochondria are chief metabolic organelles with strong implications in aging that also coordinate broad physiological functions, in part, using peptides that are encoded within their independent genome. However, mitochondrial-encoded factors that actively regulate aging are unknown. Here, we report that mitochondrial-encoded MOTS-c can significantly enhance physical performance in young (2 mo.), middle-age (12 mo.), and old (22 mo.) mice. MOTS-c can regulate (i) nuclear genes, including those related to metabolism and proteostasis, (ii) skeletal muscle metabolism, and (iii) myoblast adaptation to metabolic stress. We provide evidence that late-life (23.5 mo.) initiated intermittent MOTS-c treatment (3x/week) can increase physical capacity and healthspan in mice. In humans, exercise induces endogenous MOTS-c expression in skeletal muscle and in circulation. Our data indicate that aging is regulated by genes encoded in both of our co-evolved mitochondrial and nuclear genomes.

Faecal proteomics targeting biomarkers of immunity and inflammation have demonstrated clinical application for the identification of changes in gastrointestinal function. However, there are limited comprehensive analyses of the host faecal proteome and how it may be influenced by dietary factors. To examine this, the Homo sapiens post-diet proteome of older males was analysed at the completion of a 10-week dietary intervention, either meeting the minimum dietary protein recommendations (RDA; n = 9) or twice the recommended dietary allowance (2RDA, n = 10). The host faecal proteome differed markedly between individuals, with only a small subset of proteins present in ≥ 60% of subjects (14 and 44 proteins, RDA and 2RDA, respectively, with only 7 common to both groups). No differences were observed between the diet groups on the profiles of host faecal proteins. Faecal proteins were detected from a wide range of protein classes, with high inter-individual variation and absence of obvious impact in response to diets with markedly different protein intake. This suggests that well-matched whole food diets with two-fold variation in protein intake maintained for 10 weeks have minimal impact on human faecal host proteins., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gathercole, Grosvenor, Lee, Thomas, Mitchell, Zeng, D'Souza, Ramzan, Sharma, Knowles, Roy, Sjödin, Wagner, Milan, Mitchell and Cameron-Smith.)

Introduction: Maternal obesity during pregnancy is associated with adverse changes in body composition and metabolism in the offspring. We hypothesise that supplementation during pregnancy of overweight and obese women may help prevent the development of greater adiposity and metabolic dysfunction in children. Previous clinical trials investigating fish oil supplementation in pregnancy on metabolic outcomes and body composition of the children have not focused on the pregnancies of overweight or obese women., Methods and Analysis: A double-blind randomised controlled trial of fish oil (providing 3 g/day of n-3 polyunsaturated fatty acids) versus an equal volume of olive oil (control) taken daily from recruitment until birth, and in breastfeeding mothers, further continued for 3 months post partum. Eligible women will have a singleton pregnancy at 12-20 weeks' gestation and be aged 18-40 years with body mass index ≥25 kg/m 2 at baseline. We aim to recruit a minimum of 128 participants to be randomised 1:1. Clinical assessments will be performed at baseline and 30 weeks of pregnancy, including anthropometric measurements, fasting metabolic markers, measures of anxiety, physical activity, quality of life and dietary intake. Subsequent assessments will be performed when the infant is 2 weeks, 3 months and 12 months of age for anthropometry, body composition (dual-energy X-ray absorptiometry (DXA)) and blood sampling. The primary outcome of the study is a between-group difference in infant percentage body fatness, assessed by DXA, at 2 weeks of age. Secondary outcomes will include differences in anthropometric measures at each time point, percentage body fat at 3 and 12 months and homeostatic model assessment of insulin resistance at 3 months. Statistical analysis will be carried out on the principle of intention to treat., Ethics and Dissemination: This trial was approved by the Northern A Health and Disabilities Ethics Committee, New Zealand Ministry of Health (17/NTA/154). Results will be published in a peer-reviewed journal., Trial Registration Number: ACTRN12617001078347p; Pre-results., Competing Interests: Competing interests: During the conduct of the study, BBA reports an Australasian Pediatric Endocrine Care Grant, and MH reports grants from Health Research Council of New Zealand, L’Oreal UNESCO FWIS and National Science Challenge–Healthier Lives, outside the submitted work. The study sponsor is the Liggins Institute, University of Auckland., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Dietary intake of iron is known to be associated with impaired glucose metabolism. However, its involvement in derangements of glucose metabolism after acute pancreatitis (AP) is not completely understood. The aim was to investigate the association between dietary iron intake and markers of glucose metabolism in individuals after an attack of AP. Fasting blood samples were collected to analyse markers of glucose metabolism (fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c)). The EPIC-Norfolk food frequency questionnaire was used to determine the habitual intake of dietary iron (total, haem, and non-haem). Multivariable linear regression analyses were conducted and six statistical models were built to adjust for covariates. A total of 109 individuals after AP were studied in a cross-sectional fashion. Total iron (β (95% confidence interval) = -0.19 (-0.35, -0.05); p = 0.01 in the most adjusted model) and non-haem iron (β (95% confidence interval) = -0.19 (-0.33, -0.04); p = 0.03 in the most adjusted model) were significantly associated with FPG, consistently in all adjusted model. Total iron and non-haem iron did not have consistent significant associations with HbA1c. Dietary haem iron intake was not associated with either FPG or HbA1c. Habitual intake of dietary iron is inversely associated with FPG in individuals after an attack of AP and may be involved in the pathogenesis of new-onset diabetes after pancreatitis. Prospective longitudinal studies are now warranted to unveil the specific mechanism underlying the involvement of dietary iron.

Multivitamin and mineral (MVM) supplements are frequently used amongst older populations to improve adequacy of micronutrients, including B-vitamins, but evidence for improved health outcomes are limited and deficiencies remain prevalent. Although this may indicate poor efficacy of supplements, this could also suggest the possibility for altered B-vitamin bioavailability and metabolism in older people. This open-label, single-arm acute parallel study, conducted at the Liggins Institute Clinical Research Unit in Auckland, compared circulatory and urinary B-vitamer responses to MVM supplementation in older (70.1 ± 2.7 y, n = 10 male, n = 10 female) compared to younger (24.2 ± 2.8 y, n = 10 male, n = 10 female) participants for 4 h after the ingestion of a single dose of a commercial MVM supplement and standardized breakfast. Older adults had a lower area under the curve (AUC) of postprandial plasma pyridoxine ( p = 0.02) and pyridoxal-5'phosphate ( p = 0.03) forms of vitamin B 6 but greater 4-pyridoxic acid AUC ( p = 0.009). Urinary pyridoxine and pyridoxal excretion were higher in younger females than in older females (time × age × sex interaction, p < 0.05). Older adults had a greater AUC increase in plasma thiamine ( p = 0.01), riboflavin ( p = 0.009), and pantothenic acid ( p = 0.027). In older adults, there was decreased plasma responsiveness of the ingested (pyridoxine) and active (pyridoxal-5'phosphate) forms of vitamin B 6 , which indicated a previously undescribed alteration in either absorption or subsequent metabolic interconversion. While these findings cannot determine whether acute B 6 responsiveness is adequate, this difference may have potential implications for B 6 function in older adults. Although this may imply higher B vitamin substrate requirements for older people, further work is required to understand the implications of postprandial differences in availability.

Background: Intolerances to bovine dairy are a motivating factor in consumers seeking alternate-or replacement-dairy beverages and foods. Sheep milk (SM) is an alternate dairy source, with greater protein, although similar amino acid composition compared to cow milk (CM). Studies are yet to address the appearance of circulating amino acids following consumption of SM, relative to CM, in humans. Objective: To clinically determine the appearance of branched chain amino acids, and other amino acids, in circulation in response to equal servings of SM and CM, in females who avoid dairy products. Design: In a double-blinded, randomized, cross-over trial, 30 self-described dairy avoiding females (20-40 years) drank 650 mL of SM or CM that were reconstituted from the spray dried powders (30 and 25 g in 180 mL water, respectively) on separate occasions, following an overnight fast. After reconstitution, the energy and protein provided by SM was higher than for CM (2,140 vs. 1,649 kJ; 29.9 vs. 19.4 g protein); content of branched chain amino acids (BCAAs) were 10.5 and 6.5 mg · mL -1 , respectively. Blood samples were collected at fasting and at regular intervals over 5 h after milk consumption. Plasma amino acids were measured by HPLC. Results: 80% of subjects self-identified as lactose intolerant, and the majority (47%) "avoided drinking milk" "most of the time". SM resulted in greater plasma appearance of BCAAs at 60 min (641.1 ± 16.3 vs. 563.5 ± 14.4 μmol·L -1 ; p < 0.001) compared with CM. SM similarly resulted in elevated postprandial concentrations of the amino acids lysine, methionine, and proline, particularly at 240 min (time × milk interactions p = 0.011, 0.017, and p = 0.002, respectively). Postprandial increases in plasma alanine concentrations were sustained to 120 min after CM (time × milk interaction p = 0.001) but not after SM, despite greater quantities provided by SM. Conclusions: SM is a rich source of protein, and relative to CM, provides a greater quantity of BCAAs, with a corresponding elevation of the postprandial circulating BCAA response. SM is therefore a possible dairy alternative of benefit to those who need to increase total protein intake or for individuals with heightened protein requirements. Unique Identifier and Registry : https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375324, identifier U1111-1209-7768., (Copyright © 2020 Milan, Samuelsson, Shrestha, Sharma, Day and Cameron-Smith.)

Context: Levels of ketone bodies are altered in both acute pancreatitis and type 1 and type 2 diabetes. However, the role of ketone bodies in the pathogenesis of abnormal glucose metabolism after pancreatitis is largely unknown. Objective: To investigate the associations between ketone bodies and glucose homeostasis in individuals with post-pancreatitis prediabetes (PPP) versus normoglycaemia after pancreatitis (NAP). Methods: Fasting blood samples were analysed for acetoacetate, β -hydroxybutyrate, and markers of glucose metabolism at a median of 26 months after acute pancreatitis. A series of linear regression analyses were conducted adjusting for patient- and pancreatitis-related characteristics. Results: The study included 27 individuals with PPP and 52 with NAP. β -hydroxybutyrate was significantly associated with fasting plasma glucose ( p = .002) and explained 26.2% of its variance in PPP, but not in NAP ( p = .814; 0%). Acetoacetate was not significantly associated with fasting plasma glucose in both PPP ( p = .681) or NAP ( p = .661). Conclusions: An inverse association between β -hydroxybutyrate and fasting plasma glucose characterises PPP and this may have translational implications.

Human milk (HM) is a complex and dynamic biological fluid, which contains appreciable concentrations of the glucocorticoids, cortisol and cortisone. Experimental studies in non-human primates suggest the HM glucocorticoids' impact on infant growth and body composition. In this current study, analysis is made of the relationships between HM glucocorticoid concentrations and the infant growth and development over the first year of life. HM was collected by lactating healthy women ( n = 18), using a standardized protocol, at 2, 5, 9, and 12 months after childbirth. Cortisol and cortisone concentrations in the HM were measured using liquid chromatography mass spectrometry. Infant weight, length and head circumference were measured by standard protocols and percentage fat mass (% FM) determined by whole body bioimpedance. Cortisol and cortisone concentrations were unaltered over the analyzed lactation period (2-12 months), and were altered by infant sex. Although, HM cortisol was positively associated with infant percentage fat mass (% FM) ( p = 0.008) and cortisone positively associated with infant head circumference ( p = 0.01). For the first 12 months of life, the concentration of HM glucocorticoids levels was positively associated with infant adiposity (%FM) and head circumference. This preliminary evidence provides insight to a possible relationship between ingested HM glucocorticoids and infant body composition. Further studies are required to determine the mechanisms regulating HM glucocorticoids., (Copyright © 2020 Pundir, Gridneva, Pillai, Thorstensen, Wall, Geddes and Cameron-Smith.)

The role of micronutrients such as folate and vitamin B-12 in bone quality has been widely studied with conflicting results. Ethnicity seems to play a large role on nutrient intake, as diet varies across cultures. In this study, we examined the relationships of BMD, proximal femur strength, and bone resorption with plasma folate and vitamin B-12 in a cohort of 93 healthy postmenopausal women of Chinese-Singaporean descent. The parameters examined were areal (aBMD) and volumetric BMD (vBMD) of the proximal femur and the third lumbar vertebra (L3), total body aBMD, proximal femur bending, compressive and impact strength indices (composite strength indices) and circulating levels of C-telopeptide of type I collagen. Eighteen participants (19.4%) had aBMD in the osteoporotic range (osteoporosis group), 59 (63.4%) in the osteopenic range (osteopenia group), and the remaining 16 (17.2%) in the normal range (normal BMD group). Circulating folate levels were significantly higher in the normal BMD group compared with the osteoporosis group. Using linear regression analysis, we found that overall, aBMD and vBMD are positively associated with folate concentrations, whereas composite strength indices were positively associated with vitamin B-12 concentrations. These findings support the existing literature and suggest a link between levels of circulating folate/vitamin B-12 and BMD/bone strength in the cohort examined. Further investigation is needed to examine if individuals with inadequate circulating levels of these nutrients could decrease their risk for fragility fractures through better nutrition or vitamin supplementation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., (© 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

New Findings: What is the central question of this study? Does short-term high-intensity interval training alter the composition of the microbiome and is this associated with exercise-induced improvements in cardiorespiratory fitness and insulin sensitivity? What is the main finding and its importance? Although high-intensity interval training increased insulin sensitivity and cardiovascular fitness, it did not alter the composition of the microbiome. This suggests that changes in the composition of the microbiome that occur with prolonged exercise training might be in response to changes in metabolic health rather than driving exercise training-induced adaptations., Abstract: Regular exercise reduces the risk of metabolic diseases, and the composition of the gut microbiome has been associated with metabolic function. We investigated whether short-term high-intensity interval training (HIIT) altered the diversity and composition of the bacterial community and whether there were associations with markers of insulin sensitivity or aerobic fitness. Cardiorespiratory fitness ( V ̇ O 2 peak ) and body composition (dual energy X-ray absorptiometry scan) were assessed and faecal and fasted blood samples collected from 14 lean (fat mass 21 ± 2%, aged 29 ± 2 years) and 15 overweight (fat mass 33 ± 2%, aged 31 ± 2 years) men before and after 3 weeks of HIIT training (8-12 × 60 s cycle ergometer bouts at V ̇ O 2 peak power output interspersed by 75 s rest, three times per week). Gut microbiome composition was analysed by 16S rRNA gene amplicon sequencing. The HIIT significantly increased the aerobic fitness of both groups (P < 0.001) and improved markers of insulin sensitivity (lowered fasted insulin and HOMA-IR; P < 0.001) in the overweight group. Despite differences in the abundance of several bacterial taxa being evident between the lean and overweight group, HIIT did not affect the overall bacterial diversity or community structure (α-diversity or β-diversity). No associations were found between the top 50 most abundant bacterial genera and cardiorespiratory fitness markers; however, significant associations (P < 0.05) were observed between the abundance of the bacterial species Coprococcus&#95;3, Blautia, Lachnospiraceae&#95;ge and Dorea and insulin sensitivity markers in the overweight group. Our results suggest that short-term HIIT does not greatly impact the overall composition of the gut microbiome, but that certain microbiome genera are associated with insulin sensitivity markers that were improved by HIIT in overweight participants., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)