Artificial intelligence and prediction of cardiometabolic disease: Systematic review of model performance and potential benefits in indigenous populations.

BACKGROUND: Indigenous peoples often have higher rates of morbidity and mortality associated with cardiometabolic disease (CMD) than non-Indigenous people and this may be even more so in urban areas. The use of electronic health records and expansion of computing power has led to mainstream use of artificial intelligence (AI) to predict the onset of disease in primary health care (PHC) settings. However, it is unknown if AI and in particular machine learning is used for risk prediction of CMD in Indigenous peoples. METHODS: We searched peer-reviewed literature using terms associated with AI machine learning, PHC, CMD, and Indigenous peoples. RESULTS: We identified 13 suitable studies for inclusion in this review. Median total number of participants was 19,270 (range 911-2,994,837). The most common algorithms used in machine learning in this setting were support vector machine, random forest, and decision tree learning. Twelve studies used the area under the receiver operating characteristic curve (AUC) to measure performance. Two studies reported an AUC of >0.9. Six studies had an AUC score between 0.9 and 0.8, 4 studies had an AUC score between 0.8 and 0.7. 1 study reported an AUC score between 0.7 and 0.6. Risk of bias was observed in 10 (77 %) studies. CONCLUSION: AI machine learning and risk prediction models show moderate to excellent discriminatory ability over traditional statistical models in predicting CMD. This technology could help address the needs of urban Indigenous peoples by predicting CMD early and more rapidly than conventional methods.

Baseline characteristics of participants in the NAVKIDS2 trial: a patient navigator program in children with chronic kidney disease.

BACKGROUND: Children with chronic kidney disease (CKD) require multidisciplinary care to meet their complex healthcare needs. Patient navigators are trained non-medical personnel who assist patients and caregivers to overcome barriers to accessing health services through care coordination. This trial aims to determine the effectiveness of a patient navigator program in children with CKD. METHODS: The NAVKIDS2 trial is a multi-center, waitlisted, randomized controlled trial of patient navigators in children with CKD conducted at five sites across Australia. Children (0-16 years) with CKD from low socioeconomic status rural or remote areas were randomized to an intervention group or a waitlisted control group (to receive intervention after 6 months). The study primary and secondary endpoints include the self-rated health (SRH) (primary), and utility-based quality of life, progression of kidney dysfunction of the child, SRH, and satisfaction with healthcare of the caregiver at 6 months post-randomization. RESULTS: The trial completed recruitment in October 2021 with expected completion of follow-up by October 2022. There were 162 patients enrolled with 80 and 82 patients randomized to the immediate intervention and waitlisted groups, respectively. Fifty-eight (36%) participants were from regional/remote areas, with a median (IQR) age of 9.5 (5.0, 13.0) years, 46% were of European Australian ethnicity, and 65% were male. A total of 109 children (67%) had CKD stages 1-5, 42 (26%) were transplant recipients, and 11 (7%) were receiving dialysis. CONCLUSION: The NAVKIDS2 trial is designed to evaluate the effectiveness of patient navigation in children with CKD from families experiencing socioeconomic disadvantage. A higher resolution version of the Graphical abstract is available as Supplementary information.

Study protocol for Vascular Access outcome measure for function: a vaLidation study In hemoDialysis (VALID) : A multi-center, multinational validation study to assess the accuracy and feasibility of measuring vascular access function in clinical practice.

BACKGROUND: A functioning vascular access (VA) is crucial to providing adequate hemodialysis (HD) and considered a critically important outcome by patients and healthcare professionals. A validated, patient-important outcome measure for VA function that can be easily measured in research and practice to harvest reliable and relevant evidence for informing patient-centered HD care is lacking. Vascular Access outcome measure for function: a vaLidation study In hemoDialysis (VALID) aims to assess the accuracy and feasibility of measuring a core outcome for VA function established by the international Standardized Outcomes in Nephrology (SONG) initiative. METHODS: VALID is a prospective, multi-center, multinational validation study that will assess the accuracy and feasibility of measuring VA function, defined as the need for interventions to enable and maintain the use of a VA for HD. The primary objective is to determine whether VA function can be measured accurately by clinical staff as part of routine clinical practice (Assessor 1) compared to the reference standard of documented VA procedures collected by a VA expert (Assessor 2) during a 6-month follow-up period. Secondary outcomes include feasibility and acceptability of measuring VA function and the time to, rate of, and type of VA interventions. An estimated 612 participants will be recruited from approximately 10 dialysis units of different size, type (home-, in-center and satellite), governance (private versus public), and location (rural versus urban) across Australia, Canada, Europe, and Malaysia. Validity will be measured by the sensitivity and specificity of the data acquisition process. The sensitivity corresponds to the proportion of correctly identified interventions by Assessor 1, among the interventions identified by Assessor 2 (reference standard). The feasibility of measuring VA function will be assessed by the average data collection time, data completeness, feasibility questionnaires and semi-structured interviews on key feasibility aspects with the assessors. DISCUSSION: Accuracy, acceptability, and feasibility of measuring VA function as part of routine clinical practice are required to facilitate global implementation of this core outcome across all HD trials. Global use of a standardized, patient-centered outcome measure for VA function in HD research will enhance the consistency and relevance of trial evidence to guide patient-centered care. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03969225. Registered on 31st May 2019.

NAVKIDS2 trial: a multi-centre, waitlisted randomised controlled trial of a patient navigator intervention in children with chronic kidney disease - statistical analysis plan and update to the protocol.

BACKGROUND: This update summarises key changes made to the protocol since the publication of the original protocol for the NAVKIDS2 trial of patient navigators for children with chronic kidney disease (CKD) experiencing social disadvantage and provides the statistical analysis plan (SAP) which has not previously been published. METHODS/DESIGN: The original protocol was published in BMC Nephrology ( https://doi.org/10.1186/s12882-019-1325-y ) prior to the commencement of trial recruitment. During the course of the trial, some key methodological changes needed to be made including changes to eligibility criteria (addition of patients with CKD stages 1-2, broadening of financial status eligibility criterion, addition of patients living in rural/remote areas, modification of age eligibility to 0-16 years, addition of limits related to the language spoken by family, guidance regarding families with multiple eligible children), changes to sites, reduction of sample size, addition of virtual options for consent and study procedures in response to the COVID-19 pandemic, removal of staggered recruitment across sites, addition of outcomes, and changes to the timing and number of assessments. This update summarises the changes made and their rationale and provides the detailed plan for statistical analysis of the trial. These changes have been finalised prior to the completion of study follow-up and the commencement of data analysis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618001152213 . Prospectively registered on 12 July 2018.

The effect of an orally-dosed Caralluma Fimbriata extract on appetite control and body composition in overweight adults.

To examine the effect of a Caralluma Fimbriata extract (CFE) on biomarkers of satiety and body composition in overweight adults. A double-blind, randomised, placebo controlled trial to examine the effect of a Caralluma Fimbriata extract (CFE) on biomarkers of satiety and body composition in overweight adults. Eighty-three men and women aged between 20 and 50 years of age completed 16 weeks of daily supplementation with either CFE or placebo. Plasma cardiometabolic (lipid profile, glucose, insulin) and satiety (ghrelin, leptin, neuropeptideY) biomarkers, body composition, diet history and gastrointenstinal function were assessed at baseline, weeks 4, 8, 12 and 16. Subjects in the CFE and placebo groups were well matched and predominatly female 93% and 87.5%, with a mean age of 40.9 ± 6.7 and 39.5 ± 7.5 years and body mass index (BMI) of 30.0 ± 3.1 and 30.2 ± 2.9 kg/m2 respectively. There was a significant difference in plasma leptin concentration change between groups at week 16 (p = 0.04), with the placebo group increasing concentration (2.27 ± 4.80 ng/mL) while the CFE group (0.05 ± 4.69 ng/mL) remained the same. At week 16, the CFE group had significantly reduced their calorie intake from baseline compared to the placebo group (245 cal vs 15.8 cal respectively p < 0.01). The CFE group also had a significant reduction in waist circumference of 2.7 cm compared to an increase of 0.3 cm in the placebo group (p = 0.02). A weight increase from baseline was seen in the placebo group that was not observed in the CFE group (1.33 kg weight gain vs 0.37 kg weight loss respectively; p = 0.03). The placebo group also had a significant increase in fat mass, android fat mass, BMI and leptin compared to the CFE group (p = 0.04, 0.02, < 0.01 respectively). CFE was effective at maintaining bodyweight during a non-calorie controlled diet compared to a placebo. The mechanism responsible for this action is requiring further research and could be due to an increase in satiety receptor sensitivity.

Curcumin Improves Delayed Onset Muscle Soreness and Postexercise Lactate Accumulation.

The efficacy of curcumin supplementation is traditionally limited due to its poor bioavailability. Despite this, curcumin has previously been shown to improve biomarkers of muscle damage. The addition of a novel drug delivery system that improves bioavailability could improve exercise recovery. The purpose of this randomized double-blind placebo-controlled study was to assess the effect of curcumin (combined with LipiSperse) when consumed as a drink on exercise recovery in recreationally trained healthy males aged 18-35 yrs. The study included 28 young healthy males with strength training experience. The participants undertook lower limb resistance exercise to exhaustion. Fourteen participants received curcumin dispersed in water pre and postexercise and 14 received a matched placebo drink. Pain (visual analogue scale), thigh circumference (TC), lactate, creatine kinase, lactate dehydrogenase, high sensitivity C-reactive protein, myoglobin, interleukin-6, interleukin-10, and tumor necrosis factor-alpha were assessed pre, postexercise and 1, 2, 3, 24, 48, and 72 h postexercise. There was less appearance of postexercise capillary lactate in the curcumin group compared to placebo (7.4 vs 8.8 mmol/L). The placebo group rated overall muscle pain as higher compared to the curcumin group at 48- and 72-h postexercise. TC was reduced in the curcumin group compared to the placebo group at 24- and 48-h postexercise. The results suggest curcumin may facilitate a quicker return to exercise training and/or allow a higher training intensity than a placebo by reducing postexercise pain, modulating inflammatory pathways and reducing lactate accumulation in an exercising population.

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and exercise.

Chronic metabolic health diseases are increasing worldwide placing strain on healthcare systems and importantly, impacting individuals' quality of life. It is well established that many chronic diseases are associated with inflammation and oxidative stress. Exercise is a known strategy to manage and treat inflammation in animals and humans. Understanding the mechanisms which cause acute and chronic changes to systems via various exercise protocols may provide insights into how we can better clinically manage patients with inflammatory and oxidative stress associated diseases. Nrf2 is a basic leucine transcription factor which regulates the expression of antioxidant proteins to protect against damage caused by electrophilic or oxidative stress. The aim of this narrative review is to provide an overview of the literature which has investigated the relationship between acute and chronic exercise training and Nrf2 protein, mRNA and Nrf2-ARE binding activity. This narrative review presents analysis of twenty-nine articles presenting studies using animals and humans. Findings from animal models suggest that exercise increases all molecular aspects of the Nrf2-ARE pathway in all tissues studied. It was noted that there seems to be an age-related decline in Nrf2 protein upregulation with exercise training. In humans, however, there is a lack of evidence to support this claim.

High day-to-day and diurnal variability of oxidative stress and inflammation biomarkers in people with type 2 diabetes mellitus and healthy individuals.

Objective: Assess the variability and differences in oxidative stress, antioxidant, and inflammatory biomarkers in people with type 2 diabetes mellitus (T2D) and healthy controls. Methods:: Ten men and women diagnosed with T2D and ten healthy matched controls (CON) were recruited. Participants had venous blood taken at six different time points on different days, three in the morning (after overnight fast) and three in the afternoon. Inflammation (IL-6, 8, 10 and TNF-α), oxidative stress/antioxidant biomarkers (F2-isoprostanes, protein carbonyls, total antioxidant capacity (TAC), glutathione peroxidase activity, IL-6, 8 & 10 and TNF-α) were assessed. Results:: Biomarker concentrations were similar between groups. There was large variability in nearly all biomarkers for both groups. For inflammatory measures, intra-individual coefficients of variation (CV) ranged from 64.0-92.1% and 100.9-259.0% for inter-individual differences. CVs for oxidative stress markers were lower (7.4-31.2% for intra-individual and 8.6-43.0% for inter-individual). TAC had the lowest intra-individual CV - 7% for T2D and 8% for CON. Protein carbonyls were more variable in the afternoon (34% CV) compared to morning (24% CV) in CON. IL-6 intra-individual CV was different between groups for afternoon measurements (93% T2D, 60% CON). Conclusion:: Oxidative stress and inflammatory biomarkers show considerable variation in both T2D and healthy populations. Trial registration: ClinicalTrials.gov identifier: NCT01206725.

Fibre Intake Is Independently Associated with Increased Circulating Interleukin-22 in Individuals with Metabolic Syndrome.

The positive effects of dietary fibre on gut barrier function and inflammation have not been completely elucidated. Mice studies show gut barrier disruption and diet-induced insulin resistance can be alleviated by cytokine interleukin-22 (IL-22). However, little is known about IL-22 in humans and its association with gut-beneficial nutrients like fibre. We investigated whether fibre intake was associated with circulating levels of IL-22 in 48 participants with metabolic syndrome (MetS). Bivariate analysis was used to explore associations between circulating IL-22, fibre intake, MetS factors, body composition, and cardiorespiratory fitness (peak oxygen uptake, V ˙ O2peak). Hierarchical multiple regression (HMR) was used to test the independent association of fibre intake with circulating IL-22, adjusting for variables correlated with IL-22. Circulating IL-22 was positively associated with fibre intake (rs = 0.393, p < 0.006). The HMR-adjusted model explained 40% of circulating IL-22 variability, and fibre intake significantly improved the prediction model by 8.4% (p < 0.022). Participants with fibre intake above median intake of 21.5 g/day had a significantly higher circulating IL-22 than the lower intake group (308.3 ± 454.4 vs. 69.0 ± 106.4 pg/mL, p < 0.019). Fibre intake is independently associated with increased circulating IL-22 in individuals with MetS. Findings warrant further investigations to evaluate whether changes in dietary fibre intake alter circulating IL-22, and its effects on health outcomes.

The association between metabolic syndrome severity and oxidative stress induced by maximal exercise testing - a cross-sectional study.

Purpose: Oxidative stress (OS) has been implicated in the pathogenesis of metabolic syndrome (MetS). The acute change in OS biomarkers due to exercise, known as exercise-induced OS (EIOS), is postulated to be a more appropriate marker of OS compared to spot OS measures. These studies objectives were to investigate EIOS in participants with MetS and compare the associations between EIOS, spot OS measures and MetS severity. Methods: Sixty-three participants with MetS had MetS severity assessed using the MetS Z-score. Participants undertook a cardiorespiratory fitness test ( V O2peak) to volitional exhaustion (∼8-12 minutes). Plasma OS (total F2-isoprostanes (IsoP), protein carbonyls (PCs)) and antioxidant (glutathione peroxidase (GPx), total antioxidant status (TAS)) biomarkers were measured from samples obtained before and five minutes post- V O2peak test. Wilcoxon's signed-rank tests were used to determine changes in OS markers. Results: There were no significant (p > 0.05) changes in OS or antioxidant biomarkers from pre- to post-exercise (median (interquartile range): IsoP -15.5 (-71.8 to 47.8) pg/mL; PC -0.01 (-0.16 to 0.13) nmol/mg protein; GPx 0.76 (-4.94 to 9.82) U/L, TAS 0.03 (0.00-0.05) mmol/L). Conclusions: A V O2peak test to exhaustion failed to induce OS in participants with MetS. There were no associations between MetS severity and spot OS or EIOS biomarkers.

Low-Volume High-Intensity Interval Training Is Sufficient to Ameliorate the Severity of Metabolic Syndrome.

BACKGROUND: High-intensity interval training (HIIT) is superior to moderate-intensity continuous training (MICT) at improving cardiometabolic risk. However, the optimal volume of HIIT to reduce the severity of the metabolic syndrome (MetS) has yet to be investigated. The aim of this study was to examine the impact of different volumes of HIIT and MICT on MetS severity (MetS z-score). METHODS: This was a substudy of the "Exercise in prevention of Metabolic Syndrome" (EX-MET) multicenter trial, reporting data collected at the Brisbane site. Ninety-nine adults diagnosed with MetS were randomized to one of the following 16-week interventions: (1) MICT [n = 34, 30 min at 60%-70% heart rate (HR) peak/session, 150 min/week]; (2) 4HIIT (n = 34, 4 × 4 min bouts at 85%-95% HR peak, interspersed with 3 min active recovery at 50%-70% HR peak, 114 min/week); or (3) 1HIIT (n = 31, 1 × 4 min bout at 85%-95% HR peak, 51 min/week). Z-scores were derived from levels of MetS risk factors before and after the intervention. RESULTS: Eighty-one participants completed post-testing (MICT, n = 26; 4HIIT, n = 28, 1HIIT, n = 27). After excluding 16 participants who had a change in medication dosage or type during the intervention, a total of 65 participants were included in the analysis [MICT, n = 22, age 55 ± 10 years, body mass index (BMI) 32 ± 6 kg/m; 4HIIT, n = 22, 56 ± 10 years, 35 ± 9 kg/m2; 1HIIT, n = 21, 57 ± 8 years, 32 ± 5 kg/m). MetS severity reduced following all interventions (pre- to post-MetS z-score: MICT, 1.80 ± 1.93 to 0.90 ± 1.93; 4HIIT, 2.75 ± 2.56 to 2.17 ± 2.71; 1HIIT, 2.48 ± 3.38 to 0.84 ± 2.98), with no significant differences between groups. There were no reported adverse events that were directly related to the exercise interventions. CONCLUSIONS: Low-volume HIIT (51 min/week) was as effective as high-volume HIIT (114 min/week) and MICT (150 min/week) in ameliorating MetS severity.

Exercise intensity, redox homeostasis and inflammation in type 2 diabetes mellitus.

OBJECTIVES: To compare 12 weeks of exercise training at two intensities on oxidative stress, antioxidants and inflammatory biomarkers in patients with type 2 diabetes (T2D). DESIGN: Randomized trial. METHODS: Thirty-six participants with T2D were randomized to complete either 12 weeks of treadmill based high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT), followed by 40 weeks of home-based training at the same intensities. Plasma inflammation, oxidative stress and antioxidant biomarkers (total F2-isoprostanes, protein carbonyls, total antioxidant capacity, glutathione peroxidase activity, interleukin-10, interleukin-6, interleukin-8 and TNF-α) were measured at baseline, 12-weeks and 1-year. RESULTS: There were no significant changes (p>0.05) in oxidative stress and inflammation biomarkers from baseline to 12-weeks in either intervention. A decrease in total antioxidant capacity in the MICT group from baseline to 1-year by 0.05mmol/L (p=0.05) was observed. There was a significant difference (p<0.05) when groups were separated by sex with females in the MICT group having a 22.1% (p<0.05) decrease in protein carbonyls from baseline to 1-year. CONCLUSIONS: HIIT and MICT had no acute effect on oxidative stress and inflammatory biomarkers in patients with T2D.

The effect of different volumes of high-intensity interval training on proinsulin in participants with the metabolic syndrome: a randomised trial.

AIMS/HYPOTHESIS: The continuous demand for insulin in the face of insulin resistance, coupled with the glucolipotoxic environment associated with the metabolic syndrome (MetS), adversely affects the quality of insulin produced and secreted by the pancreatic beta cells. This is depicted by increased circulating intact proinsulin concentration, which is associated with increased MetS severity and risk of cardiovascular (CV) mortality. High-intensity interval training (HIIT) has been shown to reduce insulin resistance and other CV disease risk factors to a greater degree than moderate-intensity continuous training (MICT). We therefore aimed to investigate the impact of MICT and different volumes of HIIT on circulating intact proinsulin concentration. METHODS: This was a substudy of the 'Exercise in prevention of Metabolic Syndrome' (EX-MET) multicentre trial. Sixty-six individuals with MetS were randomised to 16 weeks of: (1) MICT (n = 21, 30 min at 60-70% peak heart rate [HRpeak], five times/week); (2) 4HIIT (n = 22, 4 × 4 min bouts at 85-95% HRpeak, interspersed with 3 min of active recovery at 50-70% HRpeak, three times/week); or (3) 1HIIT (n = 23, 1 × 4 min bout at 85-95% HRpeak, three times/week). A subanalysis investigated the differential impact of these training programmes on intact proinsulin concentration in MetS individuals with type 2 diabetes (MICT, n = 6; 4HIIT, n = 9; 1HIIT, n = 12) and without type 2 diabetes (MICT, n = 15; 4HIIT, n = 13; 1HIIT, n = 11). Intact proinsulin, insulin and C-peptide concentrations were measured in duplicate via ELISA, following a 12 h fast, before and after the exercise programme. Fasting intact proinsulin concentration was also expressed relative to insulin and C-peptide concentrations. RESULTS: Following the exercise training, there were no significant (p > 0.05) changes in fasting intact proinsulin concentration indices in all participants (pre- vs post-programme proinsulin, proinsulin:insulin, proinsulin:C-peptide: MICT 19% decrease, 6% increase, 4% increase; 4HIIT 19% decrease, 8% decrease, 11% decrease; 1HIIT 34% increase, 49% increase, 36% increase). In participants who did not have type 2 diabetes, only 4HIIT significantly (p < 0.05) reduced fasting intact proinsulin concentration indices from pre to post intervention (pre- vs post-programme proinsulin, proinsulin:insulin, proinsulin:C-peptide: 4HIIT 32% decrease, 26% decrease, 32% decrease, p < 0.05; 1HIIT, 14% increase, 32% increase, 16% increase, p > 0.05; MICT 27% decrease, 17% decrease, 11% decrease), with a group × time interaction effect, indicating a greater reduction in intact proinsulin indices following 4HIIT compared with MICT and 1HIIT. There were no significant (p > 0.05) changes in intact proinsulin concentration indices in participants with type 2 diabetes. CONCLUSIONS/INTERPRETATION: Higher-volume HIIT (4HIIT) improved insulin quality in MetS participants without type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01676870 FUNDING: The study was funded by the Norwegian University of Science and Technology and from an unrestricted research grant from the Coca-Cola company. Funding for the collection of physical activity data was derived from a 'UQ New Staff Start Up' grant awarded to B. Clark.

Variability of oxidative stress biomarkers in hemodialysis patients.

Oxidative stress biomarkers may have a role in the future to assist clinical decisions regarding the use of antioxidant therapies and their efficacy. The aims of this study were to evaluate the within and between-individual variability of plasma oxidative stress biomarkers and investigate factors affecting their variability. Plasma F2-isoprostanes and protein carbonyls were measured in 14 hemodialysis patients every 2 weeks for 10 weeks. Within-individual coefficients of variation (CVs) were isoprostanes = 30.4% (range = 6.1-66.7%) and protein carbonyls = 16.3% (8.4-29.5%). Between-individual CVs were isoprostanes = 34.4% (28.9-40.2%) and protein carbonyls = 19.5% (15.6-24.5%). There were no significant (p > 0.05) relationships between the oxidative stress biomarkers and dietary antioxidant intake, medications, clinical and demographic parameters.

Protein supplements: do they alter dietary intakes?

Effects of protein versus mixed macronutrient supplementation on total energy intake (TEI) and protein intake during an ad libitum diet were examined. Trained males undertook two, 2-week dietary interventions which were randomized, double blinded, and separated by 2 weeks. These were high-protein supplementation (HP: 1034.5 kJ energy, 29.6 g protein, 8.7 g fat and 12.3 g CHO) and standard meal supplementation (SM: 1039 kJ energy, 9.9 g protein, 9.5 g fat, and 29.4 g CHO) consumed daily following a week of baseline measures. Eighteen participants finished both interventions and one only completed HP. TEI (mean ± SD) was not different between baseline (11148 ± 3347 kJ) and HP (10705 ± 3143 kJ) nor between baseline and SM (12381 ± 3877 kJ), however, TEI was greater with SM than HP (923 ± 4015 kJ p = .043). Protein intake (%TEI) was greater with HP (22.4 ± 6.2%) than baseline (19.4 ± 5.4%; p = .008) but not SM (20.0 ± 5.0%). No differences in absolute daily protein intake were found. Absolute CHO intake was greater with SM than HP (52.0 ± 89.5 g, p = .006). No differences in fat intake were found. Body mass did not change between baseline (82.7 ± 11.2 kg) and either HP (83.1 ± 11.7 kg) or SM (82.9 ± 11.0 kg). Protein supplementation increases the relative proportion of protein in the diet, but doesn't increase the absolute amount of total protein or energy consumed. Thus some compensation by a reduction in other foods occurs. This is in contrast to a mixed nutrient supplement, which does not alter the proportion of protein consumed but does increase TEI.