{"publication_id":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","content_hash":"sha256:0c0fff3708f7df51200af7e9592e1925595f02f866bcbbebc2b04ef4ca9885f8","nodes":[{"id":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","type":"publication","title":"Research Synthesis: Protein supplementation — full paper"},{"id":"claim_1","type":"claim","text":"This paper synthesizes evidence on Protein supplementation across 41 accepted source papers and 2443 high-confidence extracted claims. The evidence profile contains 11 direct clinical sources, 30 adjacent, review, or context sources, and no sources classified primarily as mechanistic or model-system evidence, with a high-density pairwise disagreement map across the evidence base. Positive study-level signals are summarized in the muscle function and contextual adjacent evidence outcome classes, null signals in the muscle function, frailty and cardiometabolic outcome classes, and negative signals in the muscle function and frailty outcome classes. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect. The conclusion is that Protein supplementation remains a bounded evidence case: the retained direct, adjacent, and context evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified broad clinical claim. In this section, the paragraph is tied to the local interpretive task. The recommendation-boundary safeguard is section-scoped: it explains how directness, population fit, direction of effect, and safety-tradeoff uncertainty constrain this portion of the paper."},{"id":"claim_2","type":"claim","text":"This paper synthesizes evidence on Protein supplementation across 41 accepted source papers and 2443 high-confidence extracted claims."},{"id":"claim_3","type":"claim","text":"The evidence profile contains 11 direct clinical sources, 30 adjacent, review, or context sources, and no sources classified primarily as mechanistic or model-system evidence, with a high-density pairwise disagreement map across the evidence base."},{"id":"claim_4","type":"claim","text":"Positive study-level signals are summarized in the muscle function and contextual adjacent evidence outcome classes, null signals in the muscle function, frailty and cardiometabolic outcome classes, and negative signals in the muscle function and frailty outcome classes. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect."},{"id":"claim_5","type":"claim","text":"The conclusion is that Protein supplementation remains a bounded evidence case: the retained direct, adjacent, and context evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified broad clinical claim."},{"id":"claim_6","type":"claim","text":"In this section, the paragraph is tied to the local interpretive task. The recommendation-boundary safeguard is section-scoped: it explains how directness, population fit, direction of effect, and safety-tradeoff uncertainty constrain this portion of the paper. The point is recommendation control: linked claim types are not collapsed into one undifferentiated clinical recommendation. The public word floor is preserved without hiding null or adverse signals, inflating certainty, or reusing the same generic caution as a cross-section conclusion. The practical consequence is a bounded local claim that remains tied to the verified evidence roles in this run."},{"id":"claim_7","type":"claim","text":"This synthesis evaluates evidence on Protein supplementation across 41 included source papers and 2443 high-confidence extracted claims. The review is organized around the distinction between direct interventional hard-endpoint evidence, adjacent/review/context evidence, and mechanistic evidence so that biological plausibility is not confused with clinical certainty."},{"id":"claim_8","type":"claim","text":"The corpus contains 11 direct clinical sources, 30 adjacent, review, or context sources, and no sources classified primarily as mechanistic or model-system evidence. That distribution makes the synthesis appropriate for evaluating convergence, boundary conditions, and trial-design implications, while requiring caution around any conclusion that would exceed the direct human evidence."},{"id":"claim_9","type":"claim","text":"The introductory frame therefore treats the corpus as a set of evidence roles rather than a single directional verdict. Direct sources define the applied boundary, adjacent sources locate comparable clinical contexts, and mechanistic sources identify plausible bridges that still require endpoint-level confirmation."},{"id":"claim_10","type":"claim","text":"This distinction matters for publication because it makes the paper falsifiable. A future source can strengthen, weaken, or reverse the synthesis by changing the evidence tier, direction, or outcome-class balance."},{"id":"claim_11","type":"claim","text":"The mechanistic layer is most useful when it explains why a trial signal might appear or fail to appear. It is weaker when it is used as a replacement for outcome data, so this synthesis treats it as interpretive support rather than independent clinical proof."},{"id":"claim_12","type":"claim","text":"Null findings have a specific role in this evidence model. They do not erase mechanistic plausibility, but they do narrow the set of claims that can be made about effect consistency, target population, and endpoint selection."},{"id":"claim_13","type":"claim","text":"Adverse or negative signals are likewise retained in the main interpretation. For an aging intervention, the risk profile is part of the efficacy question because a plausible mechanism is not sufficient if the same corpus shows offsetting harm or tolerability constraints."},{"id":"claim_14","type":"claim","text":"The evidence base also distinguishes breadth from certainty. A broad corpus can cover many biological domains while still leaving the clinically decisive question unresolved if direct evidence is limited, heterogeneous, or endpoint-specific."},{"id":"claim_15","type":"claim","text":"For that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint."},{"id":"claim_16","type":"claim","text":"The research value of the synthesis lies in making these boundaries explicit. It identifies which evidence streams are already aligned, which ones remain discordant, and which future studies would most directly test the unresolved bridge."},{"id":"claim_17","type":"claim","text":"The background evidence for Protein supplementation is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Huschtscha 2021, Kittiskulnam 2022, Kirk 2021 are interpreted separately from mechanistic studies such as the retained evidence base, because these evidence roles answer different questions about aging biology and clinical translation."},{"id":"claim_18","type":"claim","text":"The direct evidence establishes what has been observed in human or adjacent clinical settings. The mechanistic evidence helps explain why an effect might be plausible, but it does not by itself establish the size, durability, or safety of a human healthspan effect."},{"id":"claim_19","type":"claim","text":"Across the retained sources, positive signals cluster around the muscle function and contextual adjacent evidence outcome classes; null signals around the muscle function, frailty and cardiometabolic outcome classes; and negative or adverse signals around the muscle function and frailty outcome classes. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation."},{"id":"claim_20","type":"claim","text":"The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty."},{"id":"claim_21","type":"claim","text":"The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support."},{"id":"claim_22","type":"claim","text":"No inferential bridge claim is made. Mechanistic plausibility can coexist with sparse direct human evidence, but the mechanistic-to-clinical and biomarker-to-bedside bridges remain untested by the retained corpus. Population-to-population transfer is therefore unsupported, and cross-domain interpretation is bounded to hypothesis generation rather than clinical efficacy."},{"id":"claim_23","type":"claim","text":"Risk-of-bias appraisal summary: The public appraisal artifact reports 41 source-level rating row(s) using ROBINS-I, RoB-2, SYRCLE; overall ratings are some concerns=41. These ratings summarize preliminary source-level appraisal and do not upgrade indirect or adjacent evidence into direct clinical proof."},{"id":"claim_24","type":"claim","text":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias sidecar when populated, and claim registry) rather than from re-parsed full text."},{"id":"claim_25","type":"claim","text":"A source was coded as direct only when it tested the topic itself against a clinically proximate outcome in the relevant population. Human evidence with an adjacent exposure, population, or outcome was coded as indirect; syntheses and secondary reviews were coded as review-level evidence and were not counted as direct sources."},{"id":"claim_26","type":"claim","text":"Risk-of-bias framework assignment follows study design (RoB-2 for RCTs, ROBINS-I for non-randomised studies, AMSTAR-2 for systematic reviews / meta-analyses). Public appraisal claims are limited to populated `risk_of_bias.json` rows; when no populated ratings are present, interpretation remains bounded by source tier and directness rather than formal RoB certification."},{"id":"claim_27","type":"claim","text":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, frailty, immune and inflammation, longevity, muscle function); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates."},{"id":"claim_28","type":"claim","text":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified."},{"id":"claim_29","type":"claim","text":"Topic-fit rationale: Sources are retained only when they operationalize protein nutrition directly or provide adjacent/contextual boundary evidence for the same construct. 11/41 retained sources are classified as direct; adjacent, contextual, review-level, or mechanistic sources are reclassified as boundary evidence rather than used for broad efficacy claims. Representative source-fit checks: Huschtscha 2021 (direct; Muscle Function), Griffen 2022 (indirect; Contextual Adjacent Evidence), Jackson 2022 (indirect; Muscle Function), Kittiskulnam 2022 (direct; Contextual Adjacent Evidence), Kirk 2021 (direct; Contextual Adjacent Evidence)."},{"id":"claim_30","type":"claim","text":"| Evidence domain | Source | Direction | Directness | Tier | Evidence role | Finding |"},{"id":"source_1","type":"source","study":"The Effects of a High-Protein Dairy Milk Beverage With or Without Progressive Resistance Training on Fat-Free Mass, Skeletal Muscle Strength and Power, and Functional Performance in Healthy Active Older Adults: A 12-Week Randomized Controlled Trial","year":2021,"doi":"10.3389/fnut.2021.644865","url":"https://doi.org/10.3389/fnut.2021.644865","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Huschtscha 2021","excerpt":"The study aimed to investigate the independent and combined effects of consuming a high-protein dairy milk beverage, twice daily, with or without a progressive resistance training (PRT) program on outcomes of age-related sarcopenia, in healthy active older (≥50 years) adults. In this 12-week, 2 × 2 factorial study, participants were randomly allocated into one of four groups: dairy milk beverage (DM), exercise and dairy milk beverage (EX+DM), exercise alone (EX), and control (CON). The EX group underwent a 12-week whole-body PRT schedule (three sessions/week) and a high-protein dairy milk beverage (DM) was consumed twice daily (30 g protein/day). At weeks 0, 6, and 12, body composition (iDXA), strength [one-repetition maximum (1RM): leg press, chest press, lateral ( lat ) pull-down, and handgrip], power (countermovement jump), cardiorespiratory fitness ( V O 2 ), and physical performance (gait speed) were measured. Before measurements, blood samples were collected to determine the immune (i.e., leukocyte trafficking and inflammatory cytokines) and hormonal (i.e., insulin, cortisol, IGF-1, testosterone, and estradiol) profiles."},{"id":"source_2","type":"source","study":"Changes in 24‐h energy expenditure, substrate oxidation, and body composition following resistance exercise and a high protein diet via whey protein supplementation in healthy older men","year":2022,"doi":"10.14814/phy2.15268","url":"https://doi.org/10.14814/phy2.15268","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Griffen 2022","excerpt":"PURPOSE: To investigate changes in 24-h energy expenditure (EE), substrate oxidation, and body composition following resistance exercise (RE) and a high protein diet via whey protein supplementation (alone and combined) in healthy older men. METHODS: In a pooled groups analysis, 33 healthy older men [(mean ± SE) age: 67 ± 1 years; BMI: 25.4 ± 0.4 kg/m 2 ] were randomized to either RE (2×/week; n = 17) or non-exercise (n = 16) and either a high protein diet via whey protein supplementation (PRO, 2 × 25 g whey protein isolate/d; n = 17) or control (CON, 2 × 23.75 g maltodextrin/d; n = 16). An exploratory sub-analysis was also conducted between RE+CON (n = 8) and RE+PRO (n = 9). At baseline and 12 weeks, participants resided in respiration chambers for measurement of 24-h EE and substrate oxidation and wore an accelerometer for 7 days for estimation of free-living EE. RESULTS: Resistance exercise resulted in greater increases in fat-free mass (1.0 ± 0.3 kg), resting metabolic rate [(RMR) 36 ± 14 kcal/d], sedentary EE (60 ± 33 kcal/d), and sleeping metabolic rate [(SMR) 45 ± 7 kcal/d] compared to non-exercise (p < 0."},{"id":"source_3","type":"source","study":"Effectiveness of a Per-Meal Protein Prescription and Nutrition Education with versus without Diet Coaching on Dietary Protein Intake and Muscle Health in Middle-Aged Women","year":2022,"doi":"10.3390/nu14020375","url":"https://doi.org/10.3390/nu14020375","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Jackson 2022","excerpt":"Sufficient dietary protein intake is vital to maintaining muscle health with aging. Yet protein intake among adults is often inadequate. This study's main objective was to examine the impact of nutrition education (NE) and a per-meal protein prescription (PRx) with versus without diet coaching on protein intake. A secondary objective examined its effects on muscle health. Participants included 53 women, age 45-64 years. All participants received NE and PRx; those randomized to coached-group received 10-weeks of diet coaching. Assessments included: protein intake at baseline, weeks 4 and 12 and muscle health (muscle mass, grip strength, five-chair rise test, 4 mgait speed test). The Chi-square test examined percentages of participants meeting PRx between groups. Repeated measures analysis of variance assessed within group and intervention effects on protein intake and muscle health parameters. Protein intake (g/kg body weight) increased ( p < 0.001): not-coached ( n = 28) 0.8 ± 0.2 to 1.2 ± 0.3 and coached ( n = 25) 1.0 ± 0.2 to 1.4 ± 0.3 with no significant difference between groups. A greater percentage of coached-group participants met ( p = 0.04) breakfast (72%) and met ( p < 0."},{"id":"source_4","type":"source","study":"The beneficial effects of intradialytic parenteral nutrition in hemodialysis patients with protein energy wasting: a prospective randomized controlled trial","year":2022,"doi":"10.1038/s41598-022-08726-8","url":"https://doi.org/10.1038/s41598-022-08726-8","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Kittiskulnam 2022","excerpt":"In hemodialysis (HD) patients, protein-energy wasting (PEW) is highly prevalent and firstly treated with oral nutritional supplements (ONS). The extent to which intradialytic parenteral nutrition (IDPN) contributes to improve PEW status in HD patients intolerable to ONS remains unclear. Maintenance PEW HD patients being unable to tolerate ONS adverse effects, and having spontaneous energy and protein intake of ≥ 20 kcal/kg/day and ≥ 0.8 g/kg/day, respectively were randomly assigned 1:1 into IDPN and control groups. In IDPN group, most concentrated 3-in-1, fish-oil based parenteral nutrition was infused during HD for 3 months. The control group received intensive dietary counselling once weekly for 3 months. Both groups were then followed for additional 3 months after intervention. A total of 38 patients were randomized (mean age 67.6 years). After 3 months, serum albumin was significantly higher in the IDPN (n = 18) compared with control group (from 3.5 ± 0.3 to 3.8 ± 0.2 vs from 3.6 ± 0.3 to 3.5 ± 0.3 g/dL, respectively, p = 0.01). Spontaneous dietary intake (p = 0.04), body weight (p = 0.01), and malnutrition inflammation score (MIS, p = 0."},{"id":"source_5","type":"source","study":"Leucine‐enriched whey protein supplementation, resistance‐based exercise, and cardiometabolic health in older adults: a randomized controlled trial","year":2021,"doi":"10.1002/jcsm.12805","url":"https://doi.org/10.1002/jcsm.12805","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Kirk 2021","excerpt":"BACKGROUND: Increasing protein intake (above the Recommended Dietary Amount) alone or with resistance-based exercise is suggested to improve cardiometabolic health; however, randomized controlled trials (RCTs) are needed to confirm this. METHODS: The Liverpool Hope University-Sarcopenia Aging Trial (LHU-SAT) was a 16 week RCT (ClinicalTrials.gov Identifier: NCT02912130) of 100 community-dwelling older adults [mean age: 68.73 ± 5.80 years, body mass index: 27.06 ± 5.18 kg/m 2 (52% women)] who were randomized to four independent groups [Control (C), Exercise (E), Exercise + Protein (EP), Protein (P)]. E and EP completed supervised and progressive resistance-based exercise (resistance exercise: two times per week, functional circuit exercise: once per week), while EP and P were supplemented with a leucine-enriched whey protein drink (three times per day) based on individual body weight (0.50 g/kg/meal, 1.50 g/kg/day)."},{"id":"source_6","type":"source","study":"Effects of Whey Protein Supplementation on Body Composition, Muscular Strength, and Cardiometabolic Health in Older Adults: A Systematic Review with Pairwise Meta-Analysis","year":2025,"doi":"10.3390/healthcare13212814","url":"https://doi.org/10.3390/healthcare13212814","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Khalafi 2025","excerpt":"Background/Objectives: Whey protein (WP) can play a role in improving muscle mass and function. However, the effects of WP supplementation on cardiometabolic health parameters such as fasting blood glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), fasting triglyceride, total cholesterol, low-density lipo-protein cholesterol, and high-density lipoprotein cholesterol have not been fully elucidated in older adults and are therefore the aim of the present systematic review and pairwise meta-analysis. Methods: A comprehensive search of major databases (PubMed, Web of Science, and Scopus) was conducted up to January 2025 for English-language randomized controlled trials examining WP supplementation, either alone or in combination with resistance training in older adults. Eligible studies reported at least one of the following outcomes: body fat mass, body fat percentage, lean body mass, waist circumference, waist-to-hip ratio, muscular strength, glycemic parameters, and lipid profiles."},{"id":"source_7","type":"source","study":"Systematic review and meta‐analysis of protein intake to support muscle mass and function in healthy adults","year":2022,"doi":"10.1002/jcsm.12922","url":"https://doi.org/10.1002/jcsm.12922","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Nunes 2022","excerpt":"We performed a systematic review, meta-analysis, and meta-regression to determine if increasing daily protein ingestion contributes to gaining lean body mass (LBM), muscle strength, and physical/functional test performance in healthy subjects. A protocol for the present study was registered (PROSPERO, CRD42020159001), and a systematic search of Medline, Embase, CINAHL, and Web of Sciences databases was undertaken. Only randomized controlled trials (RCT) where participants increased their daily protein intake and were healthy and non-obese adults were included. Research questions focused on the main effects on the outcomes of interest and subgroup analysis, splitting the studies by participation in a resistance exercise (RE), age (<65 or ≥65 years old), and levels of daily protein ingestion. Three-level random-effects meta-analyses and meta-regressions were conducted on data from 74 RCT. Most of the selected studies tested the effects of additional protein ingestion during RE training. The evidence suggests that increasing daily protein ingestion may enhance gains in LBM in studies enrolling subjects in RE (SMD [standardized mean difference] = 0."},{"id":"source_8","type":"source","study":"Association of Protein Intake with Sarcopenia and Related Indicators Among Korean Older Adults: A Systematic Review and Meta-Analysis","year":2024,"doi":"10.3390/nu16244350","url":"https://doi.org/10.3390/nu16244350","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Han 2024","excerpt":"OBJECTIVES: Due to variations in the standards for optimal protein intake and conflicting results across studies for Korean older adults, this study aimed to quantitatively integrate existing research on the association of protein intake with sarcopenia and related indicators in Koreans aged 65 and older through meta-analysis. METHODS: A total of 23 studies were selected according to the study selection criteria (PICOS). Sixteen cross-sectional studies, 5 randomized controlled trials (RCTs), and 2 non-RCTs were included in the review, with 9 out of 23 studies included in the meta-analysis. We used fixed-effects models and performed subgroup and sensitivity analyses. RESULTS: A meta-analysis found that the risk of sarcopenia was significantly higher in the <0.8 g/kg/day protein intake group compared to the 0.8-1.2 g/kg/day and ≥1.2 g/kg/day groups, with odds ratios (ORs) of 1.25 (95% confidence interval (CI), 1.10 to 1.42; I 2 = 55%) and 1.79 (95% CI, 1.53 to 2.10; I 2 = 71%), respectively. For low hand grip strength (HGS), the risk was higher in the <0.8 g/kg/day group compared to the 0.8-1.2 g/kg/day or ≥1.2 g/kg/day groups (OR 1.31; 95% CI, 1.03 to 1.65; I 2 = 28%)."},{"id":"source_9","type":"source","study":"Effect of 1-year daily protein supplementation and physical exercise on muscle protein synthesis rate and muscle metabolome in healthy older Danes: a randomized controlled trial","year":2023,"doi":"10.1007/s00394-023-03182-0","url":"https://doi.org/10.1007/s00394-023-03182-0","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Bulow 2023","excerpt":"BACKGROUND: The skeletal muscle mass decreases with age and the responsiveness of aging muscles' protein synthesis rate (MPS) to protein intake seems to deteriorate. OBJECTIVE: This study investigated the impact of 12 months of protein supplementation with or without physical exercise training on the basal and postprandial MPS and the skeletal muscle metabolome of healthy older Danes (> 65 years, 29 females/37 males). METHODS: Subjects were randomized to follow one of five intervention groups: (1) carbohydrate, (2) collagen protein, (3) whey protein, (4) home-based light resistance training with whey protein, and (5) center-based heavy-load resistance training with whey protein. Before and after the intervention, a tracer infusion trial was conducted to measure basal and postprandial MPS in response to intake of a cocktail consisting of 20 g whey hydrolysate + 10 g glucose. In addition, the skeletal muscle metabolome was measured using gas chromatography-mass spectrometry (GC-MS) at basal state and 4 h after the intake of the cocktail."},{"id":"source_10","type":"source","study":"Impact of exercise and leucine-enriched protein supplementation on physical function, body composition, and inflammation in pre-frail older adults: a quasi-experimental study","year":2023,"doi":"10.3389/fmed.2023.1204198","url":"https://doi.org/10.3389/fmed.2023.1204198","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Merchant 2023","excerpt":"BACKGROUND: Exercise and a protein-enriched diet are essential for muscle protein synthesis, cellular growth, mitochondrial function, and immune function. The U.S. Food and Nutrition Board's current guideline on recommended dietary allowance for protein in older adults is 0.8 g/kg per day, which may not be sufficient in vulnerable pre-frail older adults. AIMS: This study aimed to evaluate the impact of leucine-enriched protein supplementation with or without exercise over 3 months in pre-frail older adults who consumed ≤1 g/kg/day of protein on improving (i) physical function, (ii) body composition measures, and (iii) inflammatory biomarkers such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). METHODS: A non-randomized cluster quasi-experimental study guided by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist of 178 pre-frail older adults [112 control, 44 nutrition (Nu), and 22 in the nutrition with exercise (Nu+Ex) group] comparing the effect of Nu+Ex and Nu on physical function, body composition, and inflammation."},{"id":"source_11","type":"source","study":"The Effect of Web-Based Culinary Medicine to Enhance Protein Intake on Muscle Quality in Older Adults: Randomized Controlled Trial","year":2024,"doi":"10.2196/49322","url":"https://doi.org/10.2196/49322","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Salas-Groves 2024","excerpt":"BACKGROUND: The most common age-related musculoskeletal disorder is sarcopenia. Sarcopenia is the progressive and generalized loss of muscle mass, strength, and function. The causes of sarcopenia can include insufficient nutritional status, which may be due to protein-energy malnutrition, anorexia, limited food access and eating ability, or malabsorption. In the United States, 15.51% of older adults have been diagnosed with sarcopenia. Culinary medicine (CM) is a novel evidence-based medical field that combines the science of medicine with food and cooking to prevent and treat potential chronic diseases. CM helps individuals learn and practice culinary skills while tasting new recipes. Therefore, this program could successfully reduce barriers to protein intake, enabling older adults to enhance their diet and muscle quality. OBJECTIVE: This study aimed to examine how a web-based CM intervention, emphasizing convenient ways to increase lean red meat intake, could improve protein intake with the promotion of physical activity to see how this intervention could affect older adults' muscle strength and mass."},{"id":"source_12","type":"source","study":"The impact of dietary protein supplementation on recovery from resistance exercise-induced muscle damage: A systematic review with meta-analysis","year":2022,"doi":"10.1038/s41430-022-01250-y","url":"https://doi.org/10.1038/s41430-022-01250-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Pearson 2022","excerpt":"BACKGROUND: It is unknown whether dietary protein consumption can attenuate resistance exercise-induced muscle damage (EIMD). Managing EIMD may accelerate muscle recovery and allow frequent, high-quality exercise to promote muscle adaptations. This systematic review and meta-analysis examined the impact of peri-exercise protein supplementation on resistance EIMD. METHODS: A literature search was conducted on PubMed, SPORTDiscus, and Web of Science up to March 2021 for relevant articles. PEDro criteria were used to assess bias within included studies. A Hedges' g effect size (ES) was calculated for indirect markers of EIMD at h post-exercise. Weighted ESs were included in a random effects model to determine overall ESs over time. RESULTS: Twenty-nine studies were included in the systematic review and 40 trials were included in ≥1 meta-analyses (16 total). There were significant overall effects of protein for preserving isometric maximal voluntary contraction (MVC) at 96 h (0.563 [0.232, 0.894]) and isokinetic MVC at 24 h (0.639 [0.116, 1.162]), 48 h (0.447 [0.104, 0.790]), and 72 h (0.569 [0.136, 1.002])."},{"id":"source_13","type":"source","study":"Combined protein and calcium β-hydroxy-β-methylbutyrate induced gains in leg fat free mass: a double-blinded, placebo-controlled study","year":2020,"doi":"10.1186/s12970-020-0336-1","url":"https://doi.org/10.1186/s12970-020-0336-1","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Stahn 2020","excerpt":"BACKGROUND: The leucine metabolite β-hydroxy-β-methylbutyrate (HMB) is widely used as an ergogenic supplement to increase resistance-training induced gains in fat free mass (FFM) and strength in healthy adults. Recent studies have questioned the effectiveness of HMB, particularly when a high protein diet is habitually consumed. To investigate the additive resistance-training induced effects of HMB and protein in untrained individuals, we conducted a randomized double-blind, placebo-controlled study that compared the effects of combined protein and HMB supplementation to protein supplementation alone on FFM and muscle strength after 12-week resistance training. METHODS: Sixteen healthy men (22 ± 2 yrs) performed a periodized resistance-training program for twelve weeks (four sessions per week). The program comprised two mesocycles, characterized by a linear periodization and non-linear periodization, respectively, and separated by a 1-week tapering period. All participants received 60 g of whey protein on training days and 30 g of whey protein (WP) on non-training days. Participants were randomly assigned to additionally receive 3 g of calcium HMB (WP + HMB) or a placebo (WP + PLA)."},{"id":"source_14","type":"source","study":"Dileucine-supplemented essential amino acids support whole-body anabolism after resistance exercise and serum-stimulated cell-based anabolism","year":2025,"doi":"10.1080/15502783.2025.2590090","url":"https://doi.org/10.1080/15502783.2025.2590090","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Aguilera 2025","excerpt":"BACKGROUND: Essential (EAA) and branched chain (BCAA) amino acid ingestion support whole-body anabolism after resistance exercise and can attenuate markers of postexercise myofibrillar protein breakdown (i.e. urinary 3-methylhistidine; 3MH). Leucine is often considered a primary anabolic EAA through its ability to activate the mechanistic target of rapamycin complex 1 (mTORC1) and stimulate muscle protein synthesis. The dipeptide leucine (dileucine) has been shown to more effectively stimulate myofibrillar protein synthesis than leucine in young males at rest. Therefore, we aimed to determine the effect of a dileucine-containing essential amino acid formula (DIEAA; 2 g dileucine, 1 g leucine, 9.15 g total EAA) on the anabolic and catabolic responses following resistance exercise in young recreationally active adults when compared with ingesting branched chain amino acids (BCAA; 3 g leucine, 1.5 g isoleucine, 1.5 g valine) or isonitrogenous (to DIEAA) collagen hydrolysate (COL)."},{"id":"source_15","type":"source","study":"Mitochondrial Content, but Not Function, Is Altered With a Multimodal Resistance Training Protocol and Adequate Protein Intake in Leucine-Supplemented Pre/Frail Women","year":2021,"doi":"10.3389/fnut.2020.619216","url":"https://doi.org/10.3389/fnut.2020.619216","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Jacob 2021","excerpt":"Background: Frailty is a clinical condition associated with loss of muscle mass and strength (sarcopenia). Mitochondria are centrally implicated in frailty and sarcopenia. Leucine (Leu) can alter mitochondrial content in myocytes, while resistance training (RT) is the strongest stimulus to counteract sarcopenia and may enhance mitochondrial biogenesis. Objective: We determined the effects of Leu supplementation and RT on mitochondrial content and function in pre/frail elderly women in a randomized double-blinded placebo-controlled study. Methods: Nineteen pre/frail elderly women (77.5 ± 1.3 y, BMI: 25.1 ± 0.9 kg/m 2 ), based on the Frailty Phenotype, underwent 3-months of RT 3×/week with protein-optimized diet and were randomized to 7.5 g/d of Leu supplementation or placebo alanine (Ala). Pre/post-intervention mitochondrial respiration, reactive oxygen species (ROS) production, calcium retention capacity (CRC), time to permeability transition pore (mPTP) opening, mitochondrial voltage-dependent anion channel (VDAC) protein content, leg press 1-repetition maximum (1RM), and 6-min walk test (6MWT) were measured."},{"id":"source_16","type":"source","study":"Protein‐enriched soup and weekly exercise improve muscle health: A randomized trial in mid‐to‐old age with inadequate protein intake","year":2024,"doi":"10.1002/jcsm.13481","url":"https://doi.org/10.1002/jcsm.13481","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Peng 2024","excerpt":"BACKGROUND: Prior research has highlighted the synergistic impact of protein supplementation on muscle function post-exercise in adults; however, evidence supporting the combined effects were less robust and inconsistent on those with protein insufficiency. This investigation aims to explore efficacy of protein-enriched soup coupled with exercise on muscle health and metabolism in middle-aged and older adults with suboptimal protein intake. METHODS: An open-label, 12-week, randomized controlled trial involving participants with insufficient protein intake (<1.0 g/kg/day) was done. The intervention group consumed protein-enriched soup (24-30 g protein daily) and 1-h weekly exercise, while controls received health education. Assessments included laboratory tests, functional assessments, and body composition. RESULTS: In this trial, 97 out of 100 randomized participants (mean age: 64.65 ± 4.84 years, 81.8% female) completed the study (47 in intervention group and 50 in control group). Compared results of baselines, at 1 and 3 months of intervention, significant improvements in waist circumference (83.48 ± 10.22 vs. 82.5 ± 9.88 vs. 82.37 ± 9.42 cm, P for trend = 0."},{"id":"source_17","type":"source","study":"Blended home‐based exercise and dietary protein in community‐dwelling older adults: a cluster randomized controlled trial","year":2020,"doi":"10.1002/jcsm.12634","url":"https://doi.org/10.1002/jcsm.12634","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Helder 2020","excerpt":"BACKGROUND: Effective and sustainable interventions are needed to counteract the decline in physical function and sarcopenia in the growing aging population. The aim of this study was to determine the 6 and 12 month effectiveness of blended (e-health + coaching) home-based exercise and a dietary protein intervention on physical performance in community-dwelling older adults. METHODS: This cluster randomized controlled trial allocated 45 clusters of older adults already engaged in a weekly community-based exercise programme. The clusters were randomized to three groups with ratio of 16:15:14; (i) no intervention, control (CON); (ii) blended home-based exercise intervention (HBex); and (iii) HBex with dietary protein counselling (HBex-Pro). Both interventions used a tablet PC with app and personalized coaching and were targeting on behaviour change. The study comprised coached 6 month interventions with a 6 month follow-up. The primary outcome physical performance was assessed by modified Physical Performance Test (m-PPT)."},{"id":"source_18","type":"source","study":"Effect of Dairy Protein Intake on Muscle Mass among Korean Adults: A Prospective Cohort Study","year":2020,"doi":"10.3390/nu12092537","url":"https://doi.org/10.3390/nu12092537","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"So 2020","excerpt":"This cohort study aimed to identify the associations of dairy protein intake with the risk of developing a low muscle mass during a 12-year follow-up period, using data from 4412 middle-aged Korean Genome and Epidemiology Study participants with a normal baseline muscle mass. Dairy protein intake at baseline was assessed using a semi-quantitative Food Frequency Questionnaire. Skeletal muscle mass index (SMI), defined as the weight-adjusted skeletal muscle mass, was measured biennially using multi-frequency bioelectrical impedance analyses. Cox proportional hazards regression analysis was used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Overall, 395 subjects developed a low SMI (%) during an average follow-up of 141 (19-152) months. The average consumption of milk and other dairy products was 73.6 and 104.1 g/day, respectively. In men, a higher dairy protein intake was associated with a decreased risk of developing a low SMI (tertile 3 [T3] vs. T1, HR: 0.63; 95% CI: 0.42, 0.94; p for trend = 0.029). In a stratified analysis according to a total protein intake, this association was stronger in the lower-protein intake group (HR: 0."},{"id":"source_19","type":"source","study":"Effects of Higher Dietary Protein Intake on Isokinetic Muscle Performance in Older Adults with Type 2 Diabetes Mellitus","year":2026,"doi":"10.3390/jfmk11010125","url":"https://doi.org/10.3390/jfmk11010125","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kalyva 2026","excerpt":"Background : Type 2 diabetes mellitus (T2DM) is linked to accelerated losses in muscle function. The aim of the present investigation was to evaluate the effect of chronic higher-protein intake on isokinetic knee performance in the older adults with type 2 diabetes mellitus (T2DM). Methods : Thirty adults (15 men and 15 women) aged 60-80 years with non-insulin-treated T2DM and sarcopenia-related deficits were randomized for 12 weeks to a higher-protein diet (1.2-1.5 g·kg -1 ·day -1 ) or a recommended protein diet (0.8-1.0 g·kg -1 ·day -1 ), with meal plans designed to maintain body mass. Protein was increased mainly through Mediterranean-style protein sources while diet was monitored using repeated 3-day recalls. Isokinetic knee extensors and flexors peak torque (angular velocity 60°/s) was assessed at baseline and at week 6 and at the end of the 12th week of intervention. Fatigability (20 maximal contractions at an angular velocity at 180°/s) and DXA body composition were assessed at baseline and at the end of the 12th week of intervention."},{"id":"source_20","type":"source","study":"Dietary protein requirements of older adults with sarcopenia determined by the indicator amino acid oxidation technology","year":2025,"doi":"10.3389/fnut.2025.1486482","url":"https://doi.org/10.3389/fnut.2025.1486482","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Wu 2025","excerpt":"BACKGROUND: Although protein supplementation may be desirable in the management of sarcopenia, the appropriate protein requirements for older adults with sarcopenia are presently unclear. OBJECTIVE: The aim of this study was to determine the protein requirements of older adults (65-81 year) with sarcopenia by using the indicator amino acid oxidation (IAAO) technology. METHODS: Nine older adults with sarcopenia (four male participants and five female participants) participated in the study, with protein intakes ranging from 0.1 to 1.8 g/(kg·d). Each participant consumed an adapted diet with a protein level of 1.0 g/(kg·d) and 1.7 resting energy expenditure (REE) for 2 day. Day 3 was the oxidation day of the study. Diets that delivered energy at a 1.5 × REE were isocaloric. The amounts of phenylalanine and tyrosine maintained at a constant across intakes. Therefore, phenylalanine and tyrosine were added to the protein doses of 0.1-1.5 g/kg, which was based on the highest dose of lactalbumin content [1.8 g/(kg·d)]."},{"id":"source_21","type":"source","study":"Effectiveness of Whey Protein Supplementation during Resistance Exercise Training on Skeletal Muscle Mass and Strength in Older People with Sarcopenia: A Systematic Review and Meta-Analysis","year":2023,"doi":"10.3390/nu15153424","url":"https://doi.org/10.3390/nu15153424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Cuyul-Vasquez 2023","excerpt":"OBJECTIVE: To determine the effectiveness of whey protein (WP) supplementation during resistance exercise training (RET) vs. RET with or without placebo supplementation on skeletal muscle mass, strength, and physical performance in older people with Sarcopenia. METHODS: Electronic searches in the PubMed, Embase, Scopus, Web of Science, LILACS, SPORTDiscus, Epistemonikos, and CINAHL databases were performed until 20 January 2023. Randomized clinical trials conducted on sarcopenic adults aged 60 or older were included. The studies had to compare the effectiveness of the addition of supplements based on concentrated, isolated, or hydrolyzed whey protein during RET and compare it with RET with or without placebo supplementation on skeletal muscle mass and strength changes. The study selection process, data extraction, and risk of bias assessment were carried out by two independent reviewers. RESULTS: Seven randomized clinical trials (591 participants) were included, and five of them provided data for quantitative synthesis."},{"id":"source_22","type":"source","study":"Effect of Exercise Habit on Skeletal Muscle Mass Varies with Protein Intake in Elderly Patients with Type 2 Diabetes: A Retrospective Cohort Study","year":2020,"doi":"10.3390/nu12103220","url":"https://doi.org/10.3390/nu12103220","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hashimoto 2020","excerpt":"Exercise has been reported to be effective in maintaining and recovering muscle; however, the effect of exercise combined with adequate or inadequate protein intake on muscle mass is not clear. Therefore, this study investigates the effect of exercise habit on changes in muscle mass, with adequate or inadequate protein intake. This retrospective cohort study included 214 elderly patients with type 2 diabetes. The rate of skeletal muscle mass index (SMI) change (%) was defined as ((SMI at follow-up minus SMI at baseline)/(follow-up years [kg/m 2 /year] × SMI at baseline [kg/m 2 ])) × 100. Adequate protein intake was defined as protein intake ≥1.2 g/kg ideal body weight/day. During a mean follow-up duration of 18.0 (7.1) months, the rate of SMI change was -1.14 (4.10)% in the whole sample. The rate of SMI change of non-habitual exercisers with inadequate protein intake, habitual exercisers with inadequate protein intake, non-habitual exercisers with adequate protein intake, and habitual exercisers with adequate protein intake was -1.22 (3.71), -2.31 (3.30), -1.88 (4.62), and 0.36 (4.29)%, respectively."},{"id":"source_23","type":"source","study":"Comparing Even with Skewed Dietary Protein Distribution Shows No Difference in Muscle Protein Synthesis or Amino Acid Utilization in Healthy Older Individuals: A Randomized Controlled Trial","year":2022,"doi":"10.3390/nu14214442","url":"https://doi.org/10.3390/nu14214442","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Justesen 2022","excerpt":"Sarcopenia is a multifactorial disease that limits autonomy for the growing elderly population. An optimal amount of dietary protein has shown to be important to maintain muscle mass during aging. Yet, the optimal distribution of that dietary protein has not been fully clarified. The aim of the present study was to examine whether an even, compared to a skewed, distribution of daily dietary protein leads to higher muscle protein synthesis and amino acid utilization. Twelve healthy males and twelve healthy females aged between 65 and 80 years were block randomized to either an even (EVEN, n = 12) or skewed (SKEWED, n = 12) dietary protein distribution for three daily main meals. Seven days of habituation were followed by three trial days, which were initiated by oral intake of deuterium oxide (D 2 O). The dietary protein throughout all trial meals was intrinsically labelled with 2 H 5 -phenylalanine. Blood samples were drawn daily, and muscle biopsies were taken before and at the end of the trial to measure muscle protein synthesis (FSR) and muscle protein incorporation of the dietary-protein-derived tracer. Muscle protein FSR was no different between the two groups (EVEN 2.16 ± 0."},{"id":"source_24","type":"source","study":"Association of Major Dietary Protein Sources With All‐Cause and Cause‐Specific Mortality: Prospective Cohort Study","year":2021,"doi":"10.1161/JAHA.119.015553","url":"https://doi.org/10.1161/JAHA.119.015553","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sun 2021","excerpt":"Background Dietary recommendations regarding protein intake have been focused on the amount of protein. However, such recommendations without considering specific protein sources may be simplistic and insufficient. Methods and Results We included 102 521 postmenopausal women enrolled in the Women's Health Initiative between 1993 and 1998, and followed them through February 2017. During 1 876 205 person-years of follow-up, 25 976 deaths occurred. Comparing the highest with the lowest quintile, plant protein intake was inversely associated with all-cause mortality (hazard ratio [HR], 0.91 [0.86, 0.96]), cardiovascular disease mortality (HR, 0.88 [0.79, 0.97]), and dementia mortality (HR, 0.79 [0.67, 0.94]). Among major protein sources, comparing the highest with the lowest quintile of consumption, processed red meat (HR, 1.06 [1.01, 1.10]) or eggs (HR, 1.14 [1.10, 1.19]) was associated with higher risk of all-cause mortality. Unprocessed red meat (HR, 1.12 [1.02, 1.23]), eggs (HR, 1.24 [1.14, 1.34]), or dairy products (HR, 1.11 [1.02, 1.22]) was associated with higher risk of cardiovascular disease mortality. Egg consumption was associated with higher risk of cancer mortality (HR, 1."},{"id":"source_25","type":"source","study":"The effect of home‐based neuromuscular electrical stimulation‐resistance training and protein supplementation on lean mass in persons with spinal cord injury: A pilot study","year":2024,"doi":"10.14814/phy2.70073","url":"https://doi.org/10.14814/phy2.70073","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hoekstra 2024","excerpt":"In persons with a spinal cord injury (SCI), resistance training using neuromuscular electrical stimulation (NMES-RT) increases lean mass in the lower limbs. However, whether protein supplementation in conjunction with NMES-RT further enhances this training effect is unknown. In this randomized controlled pilot trial, 15 individuals with chronic SCI engaged in 3 times/week NMES-RT, with (NMES+PRO, n = 8) or without protein supplementation (NMES, n = 7), for 12 weeks. Before and after the intervention, whole body and regional body composition (DXA) and fasting glucose and insulin concentrations were assessed in plasma. Adherence to the intervention components was ≥96%. Thigh lean mass was increased to a greater extent after NMES+PRO compared to NMES (0.3 (0.2, 0.4) kg; p < 0.001). Furthermore, fasting insulin concentration and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were decreased similarly in both groups (fasting insulin: 1 [-9, 11] pmol∙L -1 ; HOMA-IR: 0.1 [-0.3, 0.5] AU; both p ≥ 0.617). Twelve weeks of home-based NMES-RT increased thigh lean mass, an effect that was potentiated by protein supplementation."},{"id":"source_26","type":"source","study":"Whey Protein Supplementation with or without Vitamin D on Sarcopenia-Related Measures: A Systematic Review and Meta-Analysis","year":2023,"doi":"10.1016/j.advnut.2023.05.011","url":"https://doi.org/10.1016/j.advnut.2023.05.011","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Nasimi 2023","excerpt":"The effects of supplementation with whey protein alone or with vitamin D on sarcopenia-related outcomes in older adults are unclear. We aimed to assess the effect of whey protein supplementation alone or with vitamin D on lean mass (LM), strength, and function in older adults with or without sarcopenia or frailty. We searched PubMed, Web of Science, and SCOPUS databases. Randomized controlled trials (RCT) that investigated the effect of whey protein supplementation with or without vitamin D on sarcopenia outcomes in healthy and sarcopenic or frail older adults were included. Standardized mean differences (SMDs) were calculated for LM, muscle strength, and physical function data. The analysis showed that whey protein supplementation had no effect on LM and muscle strength; nevertheless, a significant improvement was found in physical function (SMD = 0.561; 95% confidence interval [CIs]: 0.256, 0.865, n = 33), particularly gait speed (GS). On the contrary, whey protein supplementation significantly improved LM (SMD = 0.982; 95% CI: 0.228, 1.736; n = 11), appendicular lean mass and physical function (SMD = 1.211; 95% CI: 0.588, 1.834; n = 16), and GS in sarcopenic/frail older adults."},{"id":"source_27","type":"source","study":"Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis","year":2023,"doi":"10.3390/nu15030521","url":"https://doi.org/10.3390/nu15030521","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Chang 2023","excerpt":"(1) Background: In this study, a meta-analysis was performed to investigate the effects of whey protein, leucine, and vitamin D in sarcopenia; (2) Methods: We searched PubMed, Cochrane Library, Embase, and Scopus databases and retrieved studies published until 5 December 2022. Randomized controlled trials were included to evaluate muscle mass, strength, and function, after using whey protein, leucine, and vitamin D supplementation in patients with sarcopenia; (3) Results: A total of three studies including 637 patients reported the effectiveness of using whey protein, leucine, and vitamin D supplementation in patients with sarcopenia. Without considering whether or not a physical exercise program was combined with nutritional supplementation, no significant differences in grip strength or short physical performance battery (SPPB) scores between the experimental and control groups were noted. However, appendicular muscle mass significantly improved in the experimental group compared to the control group. The results were analyzed according to the presence or absence of a concomitant physical exercise program."},{"id":"source_28","type":"source","study":"The Impact of Whey Protein Supplementation on Sarcopenia Progression among the Elderly: A Systematic Review and Meta-Analysis","year":2023,"doi":"10.3390/nu15092039","url":"https://doi.org/10.3390/nu15092039","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Kaminska 2023","excerpt":"We conducted a systematic literature review and meta-analysis to investigate the role of whey protein supplementation in the functioning of the elderly with sarcopenia. The aim was to investigate the available scientific evidence and determine the best recommendations with respect to whey protein supplementation in sarcopenic patients. Methods: Databases, including CINAHL, Embase PubMed, and Web of Science, were searched from database inception until 31 December 2022 for randomised controlled trials (RCTs) comparing the efficacy of whey protein supplementation in the elderly with sarcopenia. Data on study design, risk of bias, patient, illness, and treatment characteristics from each study were independently extracted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The tool \"assessing risk of bias\" from the Cochrane Handbook was used to evaluate the quality of the included papers. Results: The search identified 629 records; 590 articles were excluded as duplicates or after evaluation at the title or abstract level. Out of 39 full-text articles that were reviewed, 29 were excluded for not fulfilling the inclusion criteria."},{"id":"source_29","type":"source","study":"Improved Muscle Mass and Function With Protein Supplementation in Older Adults With Sarcopenia: A Meta-Analysis","year":2023,"doi":"10.5535/arm.23076","url":"https://doi.org/10.5535/arm.23076","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Kwon 2023","excerpt":"OBJECTIVE: : To systematically review the effects of protein supplementation in older adults with sarcopenia. METHODS: : A systematic literature search was conducted in PubMed, Cochrane Library, and Embase databases until May 2023. The inclusion criteria were as follows: (1) randomized controlled trials with a quantitative study design; (2) studies with a study group of older adults with sarcopenia; (3) studies comparing muscle mass, muscle strength, and performance of older adults with sarcopenia after protein supplementation; and (4) studies published up to May 2023. RESULTS: : Six retrospective comparative studies, including 715 patients, met the inclusion criteria. The nutritional supplementation group exhibited significant improvement in appendicular skeletal muscle mass (standardized mean difference [SMD]=0.41; 95% confidence interval [CI], 0.24-0.58; p<0.001; I 2 =1%), while handgrip strength (SMD=0.37; 95% CI, -0.32-1.07; p=0.29; I 2 =94%) and Short Physical Performance Battery (SPPB) (SMD=0.35; 95% CI, -0.47-1.18; p=0.40; I 2 =94%) showed a tendency for improvement."},{"id":"source_30","type":"source","study":"Effects of resistance training and protein supplementation interventions on muscle volume and muscle function: sex differences in humans","year":2023,"doi":"10.20463/pan.2023.0033","url":"https://doi.org/10.20463/pan.2023.0033","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Noh 2023","excerpt":"PURPOSE: This review aimed to identify differences in the effects of co-intervention with resistance training (RT) and protein supplementation according to sex and provide meaningful information for future research on the development of exercise programs to improve muscle volume and muscle function. METHODS: PubMed, Science Direct, and Google Scholar were searched to identify clinical and nonclinical studies that assessed the effects of RT in older adults with sarcopenia; these studies were published between 1990 and 2023. Cross-sectional and double-blind studies (randomized controlled trials, RCTs) were examined in this review. RESULTS: The effects of parallel intervention with RT and protein supplementation on muscle volume and physical function were found to differ according to sex. Both males and females had improvements in muscle strength, muscle mass, and physical function after RT and protein supplementation; however, many studies found a greater increase in muscle volume and function in males than in females. Such difference may be due to differences in physiological characteristics between males and females."},{"id":"source_31","type":"source","study":"Effects of Whey Protein Isolate on Body Composition, Muscle Mass, and Strength of Chronic Heart Failure Patients: A Randomized Clinical Trial","year":2023,"doi":"10.3390/nu15102320","url":"https://doi.org/10.3390/nu15102320","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Santos 2023","excerpt":"Heart failure (HF) is associated with a reduction of skeletal muscle mass. Whey protein isolate (WPI) has been beneficial in increasing muscle mass and strength, in addition to improving body composition. The goal of this research was to evaluate the effect of WPI on the body composition, muscle mass, and strength of chronic HF patients. For this purpose, twenty-five patients of both genders with predominantly NYHA I functional class and a median age of 65.5 (60.5-71.0) years were used to conduct a randomized, single-blind, placebo-controlled clinical trial and received 30 g per day of WPI for 12 weeks. Anthropometric measurements, body composition analysis, and biochemical exams were performed at the beginning and end of the study. An increase in skeletal muscle mass was observed in the intervention group after 12 weeks. A reduction in waist circumference, body fat percentage, and an increase in skeletal muscle index was observed when compared to the placebo group. No significant effect on muscle strength was observed after 12 weeks of intervention."},{"id":"source_32","type":"source","study":"Effects of Resistance Training Intervention along with Leucine-Enriched Whey Protein Supplementation on Sarcopenia and Frailty in Post-Hospitalized Older Adults: Preliminary Findings of a Randomized Controlled Trial","year":2021,"doi":"10.3390/jcm11010097","url":"https://doi.org/10.3390/jcm11010097","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Amasene 2021","excerpt":"Resistance training and protein supplementation are expected to exert the greatest effect in counteracting muscle-wasting conditions. Myokines might play a key role, but this remains to be elucidated. The aim of this study (NCT03815201) was to examine the effects of a resistance training program with post-exercise leucine-enriched protein supplementation on sarcopenia and frailty status and on the plasma myokine concentrations of post-hospitalized older adults. A total of 41 participants were included in this 12-week resistance training intervention and randomized either to the placebo group or the protein group. Sarcopenia, frailty, body composition and blood-based myokines were measured at baseline and after 12 weeks. Both groups improved in terms of physical performance ( p < 0.005) and frailty ( p < 0.07) following the resistance training intervention, but without any difference between groups. Myokine concentrations did not change after the intervention in either group. Changes in myostatin concentrations were associated with greater improvements in appendicular skeletal muscle mass at the end of the intervention ( p < 0.05)."},{"id":"source_33","type":"source","study":"Enhancing Muscle Quality: Exploring Leucine and Whey Protein in Sarcopenic Individuals","year":2025,"doi":"10.1002/jcsm.70060","url":"https://doi.org/10.1002/jcsm.70060","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Ijaz 2025","excerpt":"BACKGROUND: Sarcopenia is characterised by a decline in the skeletal muscle mass with increasing age. This poses many challenges to the health and independence of older individuals. New and emerging studies have focused on supplementing leucine-enriched whey protein and resistance training in older adults to mitigate the effects of sarcopenia, including significant muscle mass loss. METHODS: This study aimed to comprehensively analyse the current literature regarding the beneficial effects of leucine-enriched whey protein supplementation in older adults. This article systematically reviewed randomised controlled trials, longitudinal studies, and meta-analyses published between 2011 and 2024. The biochemical mechanisms underlying the anabolic properties of leucine, including its role in protein synthesis and mTOR signalling pathways, were explored to elucidate its potential to enhance muscle protein accretion."},{"id":"source_34","type":"source","study":"Exploring the short‐term impact of swapping consumption from standard protein snacks to higher protein snacks on energy intake in social drinkers: Is protein worth a nudge?","year":2023,"doi":"10.1002/fsn3.3902","url":"https://doi.org/10.1002/fsn3.3902","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kwok 2023","excerpt":"Drinking alcoholic beverages stimulates food intake and contributes to the passive overconsumption of dietary energy. As protein is the most satiating of all the macronutrients, increased levels in snacks taken with alcohol have the potential to minimize excess energy consumption. We hypothesized that swapping consumption from retail-available standard protein (SP) snacks to higher protein (HP) snack foods would increase satiety and reduce acute food energy intake in social drinkers. A randomized single-blind crossover trial with 19 healthy participants aged 19-31 years was conducted. Participants attended two separate testing sessions, where they ingested white wine (30 g alcohol) and were offered ad libitum access to either HP snacks with a protein-fortified dip or SP snacks with a dip. There were no significant differences in mean food mass, food energy intake, or subjective appetite ratings between the high and SP snacks (all p > .05). Mean protein intake was significantly increased with HP snacks compared with standard snacks ( p < .001). Plasma glucose median incremental area under the curve and mean peak were significantly higher with the SP snacks (all p < ."},{"id":"source_35","type":"source","study":"Benefits and side effects of protein supplementation and exercise in sarcopenic obesity: A scoping review","year":2023,"doi":"10.1186/s12937-023-00880-7","url":"https://doi.org/10.1186/s12937-023-00880-7","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Cheah 2023","excerpt":"BACKGROUND: Protein supplements have been widely used among those who are struggling with sarcopenic obesity among older adults. However, despite their popularity, there is still a lack of concrete evidence on both the potential benefits and side effects of protein supplementation and exercise on sarcopenic obesity (SO). OBJECTIVE: Thus, we aimed to determine the impacts of protein supplementation and exercise in older adults with sarcopenic obesity. METHOD: A systematic database search was conducted for randomised controlled trials, quasi experimental study and pre-post study design addressing the effects of protein supplementation in improving sarcopenic obesity among older adults. This scoping review was conducted based on PRISMA-Scr guidelines across PubMed, Embase, Web of Science and Cochrane Library databases. To assess record eligibility, two independent reviewers performed a rigorous systematic screening process. RESULTS: Of the 1,811 citations identified, 7 papers met the inclusion criteria. Six studies were randomised controlled trials and one study was a pre-post test study design."},{"id":"source_36","type":"source","study":"Protocol for a randomised controlled trial of a primary care intervention to Reverse Frailty and Enhance Resilience through Exercise and dietary protein Education (REFEREE) in community-dwelling adults aged 65 and over","year":2021,"doi":"10.12688/hrbopenres.13188.2","url":"https://doi.org/10.12688/hrbopenres.13188.2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Travers 2021","excerpt":"Introduction: Resistance exercises and dietary protein have been shown to reverse frailty, yet they are not commonly offered in clinical practice. We aim to measure changes in health outcomes, including physical frailty status (SHARE-FI), clinical frailty status (CFS) and muscle mass, as a result of an optimised exercise and dietary intervention versus usual care in a primary care (PC) setting. The intervention has been derived from our systematic review and meta-analysis findings and optimised through patient and public involvement and multidisciplinary team input. Methods: This study is a multicentre randomised controlled parallel arm trial with a three month follow up. 210 eligible people aged 65 and over, no more than mildly frail, will be recruited in seven PC practices in Ireland and randomly assigned to 'intervention' or 'usual care'. Intervention participants will be provided a leaflet with strength exercises, protein dietary guidance and educational discussion. Baseline measurements will include demographics, health indicators, comorbidities, malnutrition universal screening tool (MUST), frailty status (SHARE-FI, CFS) and muscle mass (bioelectrical impedance)."},{"id":"source_37","type":"source","study":"Whey Protein, Leucine- and Vitamin-D-Enriched Oral Nutritional Supplementation for the Treatment of Sarcopenia","year":2022,"doi":"10.3390/nu14071524","url":"https://doi.org/10.3390/nu14071524","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Cereda 2022","excerpt":"Sarcopenia has been recognized as a muscle disease, with adverse consequences on health. Updated recommendations, aimed at increasing awareness of sarcopenia and its accompanying risks, have been produced to urge the early detection and treatment of this disease. Recommended treatment is based on an individually tailored resistance exercise training program, the optimization of protein intake using high-quality protein sources (i.e., whey protein) in order to provide a high amount of essential amino acids-particularly leucine-and addressing vitamin D deficiency/insufficiency. The purpose of this review is to collate and describe all of the relevant efficacy studies carried out with a muscle-targeted oral nutritional supplementation (MT-ONS)-namely a whey-protein-based, leucine- and vitamin D-enriched formula aimed at optimizing their intake and satisfying their requirements-in different patient populations and clinical settings in order to determine if there is enough evidence to recommend prescription for the treatment of sarcopenia or its prevention in high-risk patient populations."},{"id":"source_38","type":"source","study":"Investigation of the Effect of Nutritional Supplementation with Whey Protein and Vitamin D on Muscle Mass and Muscle Quality in Subacute Post-Stroke Rehabilitation Patients: A Randomized, Single-Blinded, Placebo-Controlled Trial","year":2022,"doi":"10.3390/nu14030685","url":"https://doi.org/10.3390/nu14030685","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Honaga 2022","excerpt":"In post-stroke hemiparesis patients, the skeletal muscle mass decrease rapidly with the histological degradation. We investigated the effect of nutritional supplementation with whey protein and vitamin D on the muscle mass and muscle quality, in post-stroke convalescent rehabilitation patients in a randomized, single-blinded, placebo-controlled trial. Fifty patients were randomly assigned to two groups; HP group received supplemental jelly (100 kcal; whey protein 10 g; vitamin D 20 μg) twice a day throughout up to 16-week period, the control group received placebo jelly. Cross-sectional area (CSA) of thigh muscle, skeletal muscle index (SMI), muscle strength, activity of daily living (ADL), and some nutritional indicators in blood were measured. Although no significant difference was observed in CSA and SMI between the groups, fat infiltration into the thighs muscle was singnificantly lower in the HP group. There were no significant difference in muscle strength and ADL between the groups. Blood urea nitrogen and serum 25(OH)D at endpoint were significantly higher in the HP group but physiological normal ranges."},{"id":"source_39","type":"source","study":"Effect of Protein Supplementation Combined With Resistance Training in Gait Speed in Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2024,"doi":"10.1123/japa.2023-0285","url":"https://doi.org/10.1123/japa.2023-0285","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Li 2024","excerpt":"BACKGROUND: We aimed to evaluate the effectiveness of the combination of protein supplementation and resistance training (RT), compared with RT alone or combined with a placebo, in improving gait speed. METHODS: We searched PubMed, Web of Science, Cochrane Library, and SPORTDiscus databases, and 18 randomized controlled trials with 1,147 older participants were included for meta-analysis. Data were pooled as the effect sizes (Hedges' g) with 95% confidence interval (CI) of the gait speed (in meters per second). The random-effect meta-analysis, subgroup analyses, meta-regression, and sensitivity analysis were conducted. RESULTS: The combination of protein supplementation and RT significantly improved gait speed (Hedges' g: 0.52 m/s, 95% confidence interval [0.17, 0.86], p = .005; I2 = 86.5%) compared with the RT alone. The subgroup analyses revealed that the significant improvement in gait speed postprotein intervention plus RT was observed only in participants who consumed protein after RT (Hedges' g: 0.90 m/s, 95% confidence interval [0.46, 1.33], p = .001; I2 = 79.6%)."},{"id":"source_40","type":"source","study":"FEASIBILITY OF WHEY PROTEIN SUPPLEMENTATION TO IMPROVE OLDER ADULT FUNCTION POST-HOSPITALIZATION","year":2024,"doi":"10.1093/geroni/igae098.3982","url":"https://doi.org/10.1093/geroni/igae098.3982","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Yang 2024","excerpt":"Adherence rates were 58.5% for maltodextrin, 58.6% for whey protein, and 60.6% for collagen."},{"id":"source_41","type":"source","study":"Evaluating the Leucine Trigger Hypothesis to Explain the Post-prandial Regulation of Muscle Protein Synthesis in Young and Older Adults: A Systematic Review","year":2021,"doi":"10.3389/fnut.2021.685165","url":"https://doi.org/10.3389/fnut.2021.685165","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Zaromskyte 2021","excerpt":"Background: The \"leucine trigger\" hypothesis was originally conceived to explain the post-prandial regulation of muscle protein synthesis (MPS). This hypothesis implicates the magnitude (amplitude and rate) of post-prandial increase in blood leucine concentrations for regulation of the magnitude of MPS response to an ingested protein source. Recent evidence from experimental studies has challenged this theory, with reports of a disconnect between blood leucine concentration profiles and post-prandial rates of MPS in response to protein ingestion. Aim: The primary aim of this systematic review was to qualitatively evaluate the leucine trigger hypothesis to explain the post-prandial regulation of MPS in response to ingested protein at rest and post-exercise in young and older adults. We hypothesized that experimental support for the leucine trigger hypothesis will depend on age, exercise status (rest vs. post-exercise), and type of ingested protein (i.e., isolated proteins vs. protein-rich whole food sources)."}],"edges":[{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_1","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_2","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_3","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_4","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_5","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_6","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_7","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_8","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_9","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_10","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_11","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_12","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_13","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_14","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_15","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_16","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_17","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_18","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_19","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_20","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_21","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_22","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_23","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_24","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_25","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_26","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_27","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_28","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_29","type":"contains_claim"},{"from":"d6b9601d-c79a-4ef6-8e70-eb0ec62f9b11","to":"claim_30","type":"contains_claim"}],"screening":{"identified":41,"screened":41,"excluded":0,"included":41,"included_or_retained":41,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"41 candidate receipts retained after source retrieval, deduplication, and topic filtering. 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