{ "$schema_version": "5.3", "review_mode": "fresh", "claim_restatement": { "index_wording": "Increasing dietary protein intake above the adult recommended allowance improves muscle strength or physical function in adults aged 60 years or older.", "entry_form": "claim", "gradeable_restatement": "Increasing dietary protein intake above the adult recommended allowance improves physical performance in adults aged at least 60 years.", "restatement_required": true, "split_into": [], "parent_claim": null, "scope_qualifiers": [ { "qualifier": "Age ≥60, baseline protein/nutrition/frailty, energy balance, exercise, dose/formulation and fixed 8–52-week primary functional horizon identifiable before outcomes", "determinable_before_outcome": true, "determined_from": "Enrollment and experimental design, before results; no responder-defined scope.", "action": "retained" } ], "original_claim": "Increasing dietary protein intake above the adult recommended allowance improves muscle strength or physical function in adults aged 60 years or older.", "restatement_note": "The original wording names strength or physical function. Physical performance is a grammatical umbrella for those registered clinical outcomes; it does not admit tracer synthesis or DXA mass as a functional crossing. The above 0.8 g/kg/day contrast, baseline eligibility and 8–52-week horizon remain unchanged." }, "hypothesis": { "name": "Protein Intake and Muscle Function in Older Adults", "central_claim": "Increasing dietary protein intake above the adult recommended allowance improves physical performance in adults aged at least 60 years.", "proposed_mechanism": "Increasing dietary protein intake above the adult recommended allowance improves muscle strength or physical function in adults aged 60 years or older.", "claimed_scope": "Adults aged 60 years or older, with baseline protein intake, malnutrition/frailty, energy balance, exercise exposure, formulation and renal disease specified before outcomes. The primary clinical inference requires a quantified contrast above 0.8 g/kg/day and strength or physical function over 8–52 weeks. Acute tracers, mixed-age studies, short rehabilitation, amino acid derivatives and multi-ingredient packages retain separate experimental scopes.", "claimed_level": [ "response", "maintenance" ], "is_conjunctive": false, "conjunctive_note": "The nominal is the clinical sufficiency proposition represented by SC3. Mechanism, superiority, additional indication and safety subclaims are separately reported and do not gate the registered efficacy claim. The original topic family and this narrower gradeable restatement are retained; no response-based exclusions are allowed." }, "rubric_routing": { "primary_rubric": "06-metabolism-aging.md", "secondary_rubrics": [], "index_notes_applied": [ "The nominal is the clinical sufficiency proposition represented by SC3. Mechanism, superiority, additional indication and safety subclaims are separately reported and do not gate the registered efficacy claim. The original topic family and this narrower gradeable restatement are retained; no response-based exclusions are allowed." ], "rubric_fit_note": "The shipped metabolism/aging rubric does not directly cover a clinical dietary-protein strength/function claim. Its explicit adaptation treats a credible randomized dietary quantity contrast affecting predefined muscle strength or physical function as a field-valid clinical perturbation; it does not demand lifespan extension. The ladder and six universal caps remain frozen. Acute MPS, nitrogen balance, lean tissue, anatomical muscle and physical function are separately interpreted; anabolic biomarkers never automatically validate the registered clinical phenotype." }, "subclaim_matrix": { "subclaims": [ { "id": "SC1", "statement": "Additional dietary protein or essential amino acids increases muscle protein synthesis in older adults.", "subclaim_type": "mechanism", "scope": "Baseline intake, anabolic resistance, dose, amino-acid composition and exercise specified", "claimed_scope": "Baseline intake, anabolic resistance, dose, amino-acid composition and exercise specified", "governing_rubric": "06-metabolism-aging.md", "key_evidence_anchor": "Tracer studies, dose response and physiological perturbation", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Controlled feeding and tracer studies show acute anabolic responses that vary by dose, composition, activity and health. MPS or nitrogen-turnover movement alone does not demonstrate sustained muscle accretion or functional benefit, and nutrient-sensing mediation is not isolated. The functional inference from acute synthesis evidence is held at Γ under the biomarker-only cap.", "rubric_adaptation": "Applied criterion: controlled nutrient delivery changes tracer-measured muscle protein synthesis. This demonstrates acute physiological response; extension to chronic muscle function retains the biomarker-only ceiling until matched functional evidence and mechanism specificity are present." }, { "id": "SC2", "statement": "Higher protein intake preserves or increases muscle mass in older adults.", "subclaim_type": "sufficiency", "scope": "Age at least 60; baseline intake and frailty specified; imaging muscle versus DXA lean mass separated", "claimed_scope": "Age at least 60; baseline intake and frailty specified; imaging muscle versus DXA lean mass separated", "governing_rubric": "06-metabolism-aging.md", "key_evidence_anchor": "Controlled longer-term mass outcomes", "hsef_level": "Ε", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Controlled older-adult nutrition studies retain positive mass/lean-tissue findings in predefined malnourished, sarcopenic or energy-deficit contexts. Other controlled trials find no mass benefit despite higher intake; DXA/BIA lean tissue is not equivalent to anatomical muscle or strength. Context-specific preservation is Ε, with source-specific body composition limits and no inference that every higher protein protocol increases muscle.", "rubric_adaptation": "Applied criterion: controlled quantity/quality exposure changes tissue-specific muscle size or appendicular lean tissue over a predefined interval, with hydration/measurement limits and clinical function reported separately. DXA or BIA is labeled as a proxy rather than histological muscle." }, { "id": "SC3", "statement": "Higher protein intake improves strength or physical function in older adults.", "subclaim_type": "sufficiency", "scope": "Age at least 60; above 0.8 g/kg/day comparator contrast; baseline nutrition, exercise and 8–52-week horizon fixed", "claimed_scope": "Age at least 60; above 0.8 g/kg/day comparator contrast; baseline nutrition, exercise and 8–52-week horizon fixed", "governing_rubric": "06-metabolism-aging.md", "key_evidence_anchor": "Controlled strength, gait, chair-rise or other functional outcomes; combined exercise interventions decomposed", "hsef_level": "Ε", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "A quantified 0.8/1.2/1.5 g/kg trial in baseline malnourished pre-frail or frail elders shows a modest gait benefit at 1.5 g/kg over 12 weeks, with the intermediate arm null. A frail protein-only 24-week trial also reports SPPB benefit while mass is unchanged, though its exact total dose is not verified in the original abstract. Controlled 0.8 vs 1.3 g/kg feeding in stable function-limited men and one-year sarcopenia trials are null. An open-label six-month advice-plus-protein-enriched-foods trial in non-malnourished community-dwelling adults with habitual intake below 1.0 g/kg adjusted body weight/day also reports a primary 400-m walk benefit, with energy intake co-increased and the per-protocol effect not significant. These map context-specific human functional causality at Ε; multi-ingredient/RT package successes cannot supply a universal protein effect.", "rubric_adaptation": "Applied criterion: a credible randomized protein quantity contrast above 0.8 g/kg/day changes prespecified strength or physical function in baseline-defined ≥60-year adults over 8–52 weeks. Matched calories, co-ingredients and exercise components determine attribution." }, { "id": "SC4", "statement": "Protein effects generalize across adequate-intake, frail and weight-loss contexts without requiring resistance training.", "subclaim_type": "generalization", "scope": "Baseline nutrition/frailty, weight-loss medication, renal disease and training specified before outcomes", "claimed_scope": "Baseline nutrition/frailty, weight-loss medication, renal disease and training specified before outcomes", "governing_rubric": "06-metabolism-aging.md", "key_evidence_anchor": "Factorial exercise/protein studies, negative strata and direct weight-loss evidence", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "General efficacy across adequate intake, frailty and medication-assisted weight loss without training is not established. Predefined nutrition, training, formulation and energy balance modify outcomes; some frail cohorts are null. The GLP-1 lean-mass protection claim needs direct protein/training results rather than DXA loss narratives. Partial physiological plausibility remains Γ, not a validated generalization rule or a blanket claim that every older person needs the same high dose.", "rubric_adaptation": "Applied criterion: prospectively measured baseline strata and factorial protein/training contrasts or medication-specific trials, with achieved intake and functional outcomes. Responder/adherence selection and cross-trial impressions do not establish generalized efficacy." } ], "aggregation_rule": "primary-subclaim", "aggregation_preregistered": true, "aggregation_rationale": "The nominal is the clinical sufficiency proposition represented by SC3. Mechanism, superiority, additional indication and safety subclaims are separately reported and do not gate the registered efficacy claim. The original topic family and this narrower gradeable restatement are retained; no response-based exclusions are allowed.", "primary_subclaim_id": "SC3", "aggregation_derivation": "The registered primary-subclaim rule selects SC3. A quantified above-RDA protein contrast produced a modest functional benefit in a baseline malnourished, pre-frail or frail population. Controlled feeding and supplementation nulls in other defined populations limit generalization, supporting Ε with Moderate confidence. Acute synthesis and lean mass do not establish universal strength preservation. Weakest-link returns Γ; primary-subclaim and scope-matched return Ε.", "aggregation_alternatives": { "weakest_link_would_return": "Γ", "primary_subclaim_would_return": "Ε", "scope_matched_would_return": "Ε", "note": "Separate narrow successes do not replace the preregistered full-scope gate." }, "index_rule_deviation": "" }, "competing_models": { "models_evaluated": [ { "rank_in_tournament": 1, "model_id": "M2", "is_nominal": false, "name": "Mechanical loading is the main functional stimulus", "core_claim": "Resistance exercise improves strength and muscle adaptation, while additional protein is a context-dependent modifier.", "explains_what_nominal_does_not": "Resistance exercise improves strength and muscle adaptation, while additional protein is a context-dependent modifier.", "strongest_supporting_evidence": [ "PRO-Elderly and a healthy 24-week training study show exercise benefits with null protein add-ons, and CALM shows null protein-only arms alongside effective heavy loading; factorial studies separate some loading and nutrition effects." ], "strongest_contradictory_evidence": [ "Positive nutrition-only trials show that training is not universally necessary for every functional benefit; CALM lacks a training-only arm and cannot quantify protein synergy." ], "hsef_level_for_this_model": "Ε", "rationale": "PRO-Elderly and a healthy 24-week training study show exercise benefits with null protein add-ons, and CALM shows null protein-only arms alongside effective heavy loading; factorial studies separate some loading and nutrition effects. Positive nutrition-only trials show that training is not universally necessary for every functional benefit; CALM lacks a training-only arm and cannot quantify protein synergy." }, { "rank_in_tournament": 2, "model_id": "M3", "is_nominal": false, "name": "Baseline malnutrition or energy deficit makes nutrition limiting", "core_claim": "Correcting antecedent nutritional deficits produces selected benefits more often than increasing already adequate intake.", "explains_what_nominal_does_not": "Correcting antecedent nutritional deficits produces selected benefits more often than increasing already adequate intake.", "strongest_supporting_evidence": [ "Park dose trial in malnourished pre-frail or frail elders and nutrition-only Tieland functional trial retain positives; stable controlled feeding nulls delimit transfer." ], "strongest_contradictory_evidence": [ "Not all frail or malnourished trials are positive, and mixed energy/micronutrient supplements do not isolate protein quantity or a deterministic baseline-response rule.", "A pooled individual-participant analysis of nine RCTs in malnourished or at-risk older adults (PMID 37432139) found no overall effect of nutritional interventions on handgrip strength, and OPTIMen and PROMISS - with similar near-allowance habitual intake - point in opposite directions, so baseline nutritional status is not yet a validated responder rule." ], "hsef_level_for_this_model": "Ε", "rationale": "Park dose trial in malnourished pre-frail or frail elders and nutrition-only Tieland functional trial retain positives; stable controlled feeding nulls delimit transfer. Not all frail or malnourished trials are positive, and mixed energy/micronutrient supplements do not isolate protein quantity or a deterministic baseline-response rule. A pooled individual-participant analysis of nine RCTs in malnourished or at-risk older adults (PMID 37432139) found no overall effect of nutritional interventions on handgrip strength, and OPTIMen and PROMISS - with similar near-allowance habitual intake - point in opposite directions, so baseline nutritional status is not yet a validated responder rule." }, { "rank_in_tournament": 3, "model_id": "M1", "is_nominal": true, "name": "Above-RDA protein improves older-adult strength or function", "core_claim": "Raising dietary protein above 0.8 g/kg/day improves some clinical muscle outcomes in older adults.", "explains_what_nominal_does_not": "Raising dietary protein above 0.8 g/kg/day improves some clinical muscle outcomes in older adults.", "strongest_supporting_evidence": [ "The 12-week 0.8/1.2/1.5 g/kg trial provides a direct dose contrast with gait benefit in a predefined vulnerable context." ], "strongest_contradictory_evidence": [ "OPTIMen direct 0.8 vs 1.3 g/kg functional null and longer supplementation nulls oppose broad generality; components and achieved intake are frequently unclear." ], "hsef_level_for_this_model": "Ε", "rationale": "The 12-week 0.8/1.2/1.5 g/kg trial provides a direct dose contrast with gait benefit in a predefined vulnerable context. OPTIMen direct 0.8 vs 1.3 g/kg functional null and longer supplementation nulls oppose broad generality; components and achieved intake are frequently unclear." }, { "rank_in_tournament": 4, "model_id": "M4", "is_nominal": false, "name": "Anabolic or lean-tissue movement can occur without functional gain", "core_claim": "Nutrient exposure changes acute MPS or lean tissue while clinical strength/function remains unchanged.", "explains_what_nominal_does_not": "Nutrient exposure changes acute MPS or lean tissue while clinical strength/function remains unchanged.", "strongest_supporting_evidence": [ "Verreijen 2015 and bed rest leucine studies show mass preservation with functional nulls, while tracer studies measure acute anabolism." ], "strongest_contradictory_evidence": [ "Tieland shows functional benefit without mass gain, and Park shows both in its context; dissociation is real but not an all purpose explanation of every trial." ], "hsef_level_for_this_model": "Γ", "rationale": "Verreijen 2015 and bed rest leucine studies show mass preservation with functional nulls, while tracer studies measure acute anabolism. Tieland shows functional benefit without mass gain, and Park shows both in its context; dissociation is real but not an all purpose explanation of every trial." } ], "tournament_summary": "Descriptive comparison; does not modify the nominal score. PMID 33564844 separates protein-only from added loading in 208 healthy older adults over one year: whey/collagen alone are ineffective, heavy training with whey improves quadriceps and strength. It favors the loading/context model over a universal protein-only interpretation, without establishing the untested protein-versus-no-protein add-on within heavy training.", "study_separating_rank1_from_rank2": "PMID 33564844 separates protein-only from added loading in 208 healthy older adults over one year: whey/collagen alone are ineffective, heavy training with whey improves quadriceps and strength. It favors the loading/context model over a universal protein-only interpretation, without establishing the untested protein-versus-no-protein add-on within heavy training.", "nominal_wins_only_by_funding_artifact": false, "level_unchanged_by_tournament": true }, "evidence_inventory": [ { "n": 1, "pmid": "33564844", "title": "The effect of daily protein supplementation, with or without resistance training for 1 year, on muscle size, strength, and function in healthy older adults: A randomized controlled trial.", "citation": "Mertz KH, Reitelseder S, Bechshoeft R et al. The effect of daily protein supplementation, with or without resistance training for 1 year, on muscle size, strength, and function in healthy older adults: A randomized controlled trial. The American journal of clinical nutrition. 2021.", "doi": "10.1093/ajcn/nqaa372", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33564844/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33564844/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID33564844", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [ "M2" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "null", "what_it_shows": "208-adult one-year randomized study finds whey/collagen alone ineffective while heavy training improves quadriceps and strength", "what_it_does_not_show": "No training-only arm isolates protein add-on; baseline adequate-intake healthy adults not all frail contexts", "confounders_present": [ "No training-only arm isolates protein add-on; baseline adequate-intake healthy adults not all frail contexts" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 2, "pmid": "34358827", "title": "Supplement-based nutritional strategies to tackle frailty: A multifactorial, double-blind, randomized placebo-controlled trial.", "citation": "Roschel H, Hayashi AP, Fernandes AL et al. Supplement-based nutritional strategies to tackle frailty: A multifactorial, double-blind, randomized placebo-controlled trial. Clinical nutrition (Edinburgh, Scotland). 2021.", "doi": "10.1016/j.clnu.2021.06.024", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/34358827/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34358827/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "ProElderly_NCT01890382", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [ "M2" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "null", "what_it_shows": "200-person pre/frail trial finds whey soy leucine or creatine do not enhance training adaptations", "what_it_does_not_show": "Shared training stimulus; baseline intake and adherence matter; no denial of exercise effect", "confounders_present": [ "Shared training stimulus; baseline intake and adherence matter; no denial of exercise effect" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 3, "pmid": "26170041", "title": "Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study: a randomized, double-blind, placebo-controlled trial.", "citation": "Bauer JM, Verlaan S, Bautmans I et al. Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study: a randomized, double-blind, placebo-controlled trial. Journal of the American Medical Directors Association. 2015.", "doi": "10.1016/j.jamda.2015.05.021", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/26170041/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26170041/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PROVIDE_NTR2323", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [ "M3", "M4" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "PROVIDE 380 has null between-arm handgrip/SPPB primary outcomes but positive secondary chair-rise and DXA lean mass", "what_it_does_not_show": "Whey/leucine/vitamin D bundled; secondary multiplicity; lean tissue not strength; no isolated total protein claim", "confounders_present": [ "Whey/leucine/vitamin D bundled; secondary multiplicity; lean tissue not strength; no isolated total protein claim" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 4, "pmid": "39771028", "title": "Obesity and Metabolic Disease Impair the Anabolic Response to Protein Supplementation and Resistance Exercise: A Retrospective Analysis of a Randomized Clinical Trial with Implications for Aging, Sarcopenic Obesity, and Weight Management.", "citation": "Nilsson MI, Xhuti D, de Maat NM et al. Obesity and Metabolic Disease Impair the Anabolic Response to Protein Supplementation and Resistance Exercise: A Retrospective Analysis of a Randomized Clinical Trial with Implications for Aging, Sarcopenic Obesity, and Weight Management. Nutrients. 2024.", "doi": "10.3390/nu16244407", "pmcid": "PMC11677392", "url": "https://pubmed.ncbi.nlm.nih.gov/39771028/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39771028/", "tier": "A", "source_tier": "A", "kind": "secondary_analysis", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Retrospective_multiingredient_parenttrial_overlap_unresolved", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Weak", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Retrospective 32-man mixed-supplement subgroup analysis links baseline obesity with weaker response and selected benefits", "what_it_does_not_show": "Post hoc responder/subgroup analysis multi-ingredients and active collagen comparator prevent pure protein attribution", "confounders_present": [ "Post hoc responder/subgroup analysis multi-ingredients and active collagen comparator prevent pure protein attribution" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [ "retrospective subgroup/secondary analysis ofa previous mixed supplement RCT" ] }, { "n": 5, "pmid": "32961041", "title": "Improving rehabilitation in sarcopenia: a randomized-controlled trial utilizing a muscle-targeted food for special medical purposes.", "citation": "Rondanelli M, Cereda E, Klersy C et al. Improving rehabilitation in sarcopenia: a randomized-controlled trial utilizing a muscle-targeted food for special medical purposes. Journal of cachexia, sarcopenia and muscle. 2020.", "doi": "10.1002/jcsm.12532", "pmcid": "PMC7749532", "url": "https://pubmed.ncbi.nlm.nih.gov/32961041/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32961041/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID32961041", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Methods:paragraph1, 1:Methods:paragraph2, 1:Methods:paragraph5, 1:Methods:paragraph13, 1:Methods:paragraph33, 1:Methods:paragraph37, 2:Results:paragraph59, 2:Results:paragraph70, 2:Results:paragraph84. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "140 sarcopenic rehabilitation patients randomized to enriched whey or isocaloric formula show improved gait and function", "what_it_does_not_show": "Variable 4–8-week discharge horizon multi-ingredients; modified ITT; short clinical scope not ordinary healthy adult supplementation", "confounders_present": [ "Variable 4–8-week discharge horizon multi-ingredients; modified ITT; short clinical scope not ordinary healthy adult supplementation" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 6, "pmid": "38479928", "title": "Effect of multicomponent intervention on malnutrition in older adults: A multicenter randomized clinical trial.", "citation": "Chen B, Zhao H, Li M et al. Effect of multicomponent intervention on malnutrition in older adults: A multicenter randomized clinical trial. Clinical nutrition ESPEN. 2024.", "doi": "10.1016/j.clnesp.2024.01.004", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38479928/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38479928/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID38479928", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "99-person nursing home ONS add-on trial finds no between-arm body composition or functional differences", "what_it_does_not_show": "Within-group improvements are not randomized treatment effects; energy/fat/protein bundled", "confounders_present": [ "Within-group improvements are not randomized treatment effects; energy/fat/protein bundled" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 7, "pmid": "32928579", "title": "Effects of adequate dietary protein with whey protein, leucine, and vitamin D supplementation on sarcopenia in older adults: An open-label, parallel-group study.", "citation": "Lin CC, Shih MH, Chen CD et al. Effects of adequate dietary protein with whey protein, leucine, and vitamin D supplementation on sarcopenia in older adults: An open-label, parallel-group study. Clinical nutrition (Edinburgh, Scotland). 2021.", "doi": "10.1016/j.clnu.2020.08.017", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/32928579/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32928579/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID32928579", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Weak", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Open label supplement versus diet counseling has similar mass/grip outcomes and selected gait improvement", "what_it_does_not_show": "Both groups target 1.2–1.5 g/kg; not RDA comparator; unblinded multi-ingredient delivery", "confounders_present": [ "Both groups target 1.2–1.5 g/kg; not RDA comparator; unblinded multi-ingredient delivery" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 8, "pmid": "36437767", "title": "De-Training Effects Following Leucine-Enriched Whey Protein Supplementation and Resistance Training in Older Adults with Sarcopenia: A Randomized Controlled Trial with 24 Weeks of Follow-Up.", "citation": "Mori H, Tokuda Y. De-Training Effects Following Leucine-Enriched Whey Protein Supplementation and Resistance Training in Older Adults with Sarcopenia: A Randomized Controlled Trial with 24 Weeks of Follow-Up. The journal of nutrition, health & aging. 2022.", "doi": "10.1007/s12603-022-1853-1", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/36437767/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36437767/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID36437767", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Sarcopenia training/supplement study finds no end-intervention arm difference but selected de-training maintenance", "what_it_does_not_show": "All groups instructed ≥1.2 g/kg; later subgroup/horizon; not an 0.8-versus-high protein comparison", "confounders_present": [ "All groups instructed ≥1.2 g/kg; later subgroup/horizon; not an 0.8-versus-high protein comparison" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 9, "pmid": "29395372", "title": "A high whey protein, vitamin D and E supplement preserves muscle mass, strength, and quality of life in sarcopenic older adults: A double-blind randomized controlled trial.", "citation": "Bo Y, Liu C, Ji Z et al. A high whey protein, vitamin D and E supplement preserves muscle mass, strength, and quality of life in sarcopenic older adults: A double-blind randomized controlled trial. Clinical nutrition (Edinburgh, Scotland). 2019.", "doi": "10.1016/j.clnu.2017.12.020", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/29395372/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29395372/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID29395372", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "60-person six-month enriched whey trial reports better BIA mass, grip and quality of life than isocaloric control", "what_it_does_not_show": "Vitamin D/E co-interventions and BIA surrogate; small sample; no isolated protein mechanism", "confounders_present": [ "Vitamin D/E co-interventions and BIA surrogate; small sample; no isolated protein mechanism" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 10, "pmid": "33216623", "title": "Effects of nutrition supplementation and physical exercise on muscle mass, muscle strength and fat mass among sarcopenic elderly: a randomized controlled trial.", "citation": "Li Z, Cui M, Yu K et al. Effects of nutrition supplementation and physical exercise on muscle mass, muscle strength and fat mass among sarcopenic elderly: a randomized controlled trial. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2021.", "doi": "10.1139/apnm-2020-0643", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/33216623/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33216623/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID33216623", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "241-person sarcopenia factorial trial reports nutrition and exercise improvements in mass/grip", "what_it_does_not_show": "Whey/fish oil/vitamin D mix; per-protocol analysis; effects need ITT and component separation", "confounders_present": [ "Whey/fish oil/vitamin D mix; per-protocol analysis; effects need ITT and component separation" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 11, "pmid": "39142111", "title": "Effect of high plant protein/peptide nutrition supplementation on knee osteoarthritis in older adults with sarcopenia: A randomized, double-blind, placebo-controlled trial.", "citation": "Wu Q, Xu Z, Huang W et al. Effect of high plant protein/peptide nutrition supplementation on knee osteoarthritis in older adults with sarcopenia: A randomized, double-blind, placebo-controlled trial. Clinical nutrition (Edinburgh, Scotland). 2024.", "doi": "10.1016/j.clnu.2024.07.037", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/39142111/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39142111/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID39142111", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Protein/peptide trial reports SPPB, grip, mass gains in sarcopenic knee OA", "what_it_does_not_show": "Ages 50–70 include outside ≥60; disease-specific proprietary mix; no separate older stratum or verified dose contrast", "confounders_present": [ "Ages 50–70 include outside ≥60; disease-specific proprietary mix; no separate older stratum or verified dose contrast" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 12, "pmid": "26353786", "title": "Collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men: a randomised controlled trial.", "citation": "Zdzieblik D, Oesser S, Baumstark MW et al. Collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men: a randomised controlled trial. The British journal of nutrition. 2015.", "doi": "10.1017/S0007114515002810", "pmcid": "PMC4594048", "url": "https://pubmed.ncbi.nlm.nih.gov/26353786/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26353786/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "ErratumIn: PMID40859798" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID26353786", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 0:Methods:paragraph11, 0:Methods:paragraph14, 0:Methods:paragraph16, 0:Methods:paragraph17, 0:Methods:paragraph24, 1:Results:paragraph0, 1:Results:paragraph1, 1:Results:paragraph9, 1:Results:paragraph13, 1:Results:paragraph16. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "53 completer men collagen plus matched training show greater DXA FFM and isokinetic strength change", "what_it_does_not_show": "Silica comparator not energy/protein matched; correction notice 2025 attached; no evidence every protein adds benefit", "confounders_present": [ "Silica comparator not energy/protein matched; correction notice 2025 attached; no evidence every protein adds benefit" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 13, "pmid": "26864356", "title": "Whey protein, amino acids, and vitamin D supplementation with physical activity increases fat-free mass and strength, functionality, and quality of life and decreases inflammation in sarcopenic elderly.", "citation": "Rondanelli M, Klersy C, Terracol G et al. Whey protein, amino acids, and vitamin D supplementation with physical activity increases fat-free mass and strength, functionality, and quality of life and decreases inflammation in sarcopenic elderly. The American journal of clinical nutrition. 2016.", "doi": "10.3945/ajcn.115.113357", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/26864356/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26864356/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID26864356", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "130 sarcopenic older adults enriched whey/EAA/vit D plus matched activity improve mass/grip/ADL versus placebo", "what_it_does_not_show": "Multicomponent nutritional intervention and short 12-week horizon; cannot isolate protein quantity or vitamin component", "confounders_present": [ "Multicomponent nutritional intervention and short 12-week horizon; cannot isolate protein quantity or vitamin component" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 14, "pmid": "28166780", "title": "Effect of a high protein diet and/or resistance exercise on the preservation of fat free mass during weight loss in overweight and obese older adults: a randomized controlled trial.", "citation": "Verreijen AM, Engberink MF, Memelink RG et al. Effect of a high protein diet and/or resistance exercise on the preservation of fat free mass during weight loss in overweight and obese older adults: a randomized controlled trial. Nutrition journal. 2017.", "doi": "10.1186/s12937-017-0229-6", "pmcid": "PMC5294725", "url": "https://pubmed.ncbi.nlm.nih.gov/28166780/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28166780/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID28166780", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph1, 1:Methods:paragraph2, 1:Methods:paragraph5, 1:Methods:paragraph7, 2:Results:paragraph4, 2:Results:paragraph8, 2:Results:paragraph15. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [ "M2", "M3" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "Weight-loss factorial study finds no protein main mass effect but selected grip/gait protein-training interactions", "what_it_does_not_show": "Actual intake contrast 1.13 vs 0.98 adjusted g/kg below prescribed separation; ages ≥55; secondary interaction multiplicity", "confounders_present": [ "Actual intake contrast 1.13 vs 0.98 adjusted g/kg below prescribed separation; ages ≥55; secondary interaction multiplicity" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 15, "pmid": "41350709", "title": "Effects of combined nutritional supplementation and exercise on proxy measures of muscle mass, strength, and function in older adults with sarcopenia: a 12-week multicentre RCT.", "citation": "Sun J, He M, Chen M et al. Effects of combined nutritional supplementation and exercise on proxy measures of muscle mass, strength, and function in older adults with sarcopenia: a 12-week multicentre RCT. Nutrition journal. 2025.", "doi": "10.1186/s12937-025-01244-z", "pmcid": "PMC12681163", "url": "https://pubmed.ncbi.nlm.nih.gov/41350709/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41350709/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41350709", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "Combined HMB/protein/vit D/exercise trial improves BIA proxies, grip and function", "what_it_does_not_show": "No factorial component control; cannot assign exercise-package benefit to protein; BIA not direct muscle", "confounders_present": [ "No factorial component control; cannot assign exercise-package benefit to protein; BIA not direct muscle" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 16, "pmid": "19850735", "title": "Effects of resistance exercise and fortified milk on skeletal muscle mass, muscle size, and functional performance in middle-aged and older men: an 18-mo randomized controlled trial.", "citation": "Kukuljan S, Nowson CA, Sanders K et al. Effects of resistance exercise and fortified milk on skeletal muscle mass, muscle size, and functional performance in middle-aged and older men: an 18-mo randomized controlled trial. Journal of applied physiology (Bethesda, Md. : 1985). 2009.", "doi": "10.1152/japplphysiol.00392.2009", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/19850735/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/19850735/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID19850735", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "18-month factorial fortified milk study has exercise benefits but no milk add-on mass/strength/function", "what_it_does_not_show": "Ages 50–79 mixed scope; exceeds registered 52-week horizon; protein/micronutrient/energy mixture", "confounders_present": [ "Ages 50–79 mixed scope; exceeds registered 52-week horizon; protein/micronutrient/energy mixture" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 17, "pmid": "42735207", "title": "Resistance versus concurrent training with three assigned protein targets in middle-aged and older women: a randomized 2 × 3 factorial trial.", "citation": "Bagheri R, Ghobadi H, Mansordehghan M et al. Resistance versus concurrent training with three assigned protein targets in middle-aged and older women: a randomized 2 × 3 factorial trial. Journal of the International Society of Sports Nutrition. 2026.", "doi": "10.1080/15502783.2026.2720742", "pmcid": "PMC13577256", "url": "https://pubmed.ncbi.nlm.nih.gov/42735207/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/42735207/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID42735207", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "2026 exercise factorial trial assigned 0.8/1.6/2.2 targets finds no protein effect on BIA or key functional outcomes", "what_it_does_not_show": "Ages 40–77; complete cases 83/108 and assigned targets not achieved intake proof; null not dose equivalence", "confounders_present": [ "Ages 40–77; complete cases 83/108 and assigned targets not achieved intake proof; null not dose equivalence" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 18, "pmid": "37972895", "title": "Higher Muscle Protein Synthesis Rates Following Ingestion of an Omnivorous Meal Compared with an Isocaloric and Isonitrogenous Vegan Meal in Healthy, Older Adults.", "citation": "Pinckaers PJ, Domić J, Petrick HL et al. Higher Muscle Protein Synthesis Rates Following Ingestion of an Omnivorous Meal Compared with an Isocaloric and Isonitrogenous Vegan Meal in Healthy, Older Adults. The Journal of nutrition. 2024.", "doi": "10.1016/j.tjnut.2023.11.004", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/37972895/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37972895/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID37972895", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "16 older adults tracer crossover finds greater acute MPS after matched omnivorous than vegan meal", "what_it_does_not_show": "Whole food matrix single meal; no chronic strength/function; not evidence plant protein cannot work", "confounders_present": [ "Whole food matrix single meal; no chronic strength/function; not evidence plant protein cannot work" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 19, "pmid": "16507602", "title": "A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly.", "citation": "Katsanos CS, Kobayashi H, Sheffield-Moore M et al. A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. American journal of physiology. Endocrinology and metabolism. 2006.", "doi": "10.1152/ajpendo.00488.2005", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/16507602/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/16507602/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID16507602", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Leucine-rich EAA mixture stimulates elderly acute MPS where lower leucine mixture did not", "what_it_does_not_show": "Short tracer rate not muscle accretion/function; groups small; specific composition and healthy context", "confounders_present": [ "Short tracer rate not muscle accretion/function; groups small; specific composition and healthy context" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 20, "pmid": "29796648", "title": "Muscle Protein Anabolic Resistance to Essential Amino Acids Does Not Occur in Healthy Older Adults Before or After Resistance Exercise Training.", "citation": "Moro T, Brightwell CR, Deer RR et al. Muscle Protein Anabolic Resistance to Essential Amino Acids Does Not Occur in Healthy Older Adults Before or After Resistance Exercise Training. The Journal of nutrition. 2018.", "doi": "10.1093/jn/nxy064", "pmcid": "PMC6251608", "url": "https://pubmed.ncbi.nlm.nih.gov/29796648/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29796648/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "ErratumIn: PMID30281119" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID29796648", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Healthy older longitudinal training study finds preserved EAA MPS response and higher basal MPS with training", "what_it_does_not_show": "No randomized high daily protein contrast; exercise benefit not supplementation effect; 2018 erratum attached", "confounders_present": [ "No randomized high daily protein contrast; exercise benefit not supplementation effect; 2018 erratum attached" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 21, "pmid": "22338078", "title": "Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults.", "citation": "Drummond MJ, Dickinson JM, Fry CS et al. Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults. American journal of physiology. Endocrinology and metabolism. 2012.", "doi": "10.1152/ajpendo.00603.2011", "pmcid": "PMC3361979", "url": "https://pubmed.ncbi.nlm.nih.gov/22338078/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/22338078/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID22338078", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Seven-day bed rest suppresses EAA-stimulated MPS/mTOR response and reduces leg lean mass", "what_it_does_not_show": "Six subjects no longer-term protein functional benefit; disuse model not universal aging resistance", "confounders_present": [ "Six subjects no longer-term protein functional benefit; disuse model not universal aging resistance" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 22, "pmid": "30475969", "title": "Protein supplementation improves muscle mass and physical performance in undernourished prefrail and frail elderly subjects: a randomized, double-blind, placebo-controlled trial.", "citation": "Park Y, Choi JE, Hwang HS. Protein supplementation improves muscle mass and physical performance in undernourished prefrail and frail elderly subjects: a randomized, double-blind, placebo-controlled trial. The American journal of clinical nutrition. 2018.", "doi": "10.1093/ajcn/nqy214", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30475969/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30475969/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID30475969", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [ "M1", "M3" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "supports", "what_it_shows": "120 malnourished pre-frail or frail elders randomized 0.8/1.2/1.5 g/kg for 12 weeks show 1.5-arm mass/gait improvement", "what_it_does_not_show": "Primary mass not gait; modest secondary effect; 1.2-arm null; findings restricted to malnutrition/frailty", "confounders_present": [ "Primary mass not gait; modest secondary effect; 1.2-arm null; findings restricted to malnutrition/frailty" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 23, "pmid": "32162241", "title": "Safety and tolerability of 6-month supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink in sarcopenic older adults.", "citation": "Bauer JM, Mikušová L, Verlaan S et al. Safety and tolerability of 6-month supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink in sarcopenic older adults. Aging clinical and experimental research. 2020.", "doi": "10.1007/s40520-020-01519-x", "pmcid": "PMC7452877", "url": "https://pubmed.ncbi.nlm.nih.gov/32162241/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32162241/", "tier": "A", "source_tier": "A", "kind": "secondary_analysis", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PROVIDE_NTR2323", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "PROVIDE follow-up reports tolerability and no observed renal decline with enriched whey drink", "what_it_does_not_show": "Same parent 380 RCT plus voluntary open-label extension; no evidence universal renal safety or new independent efficacy", "confounders_present": [ "Same parent 380 RCT plus voluntary open-label extension; no evidence universal renal safety or new independent efficacy" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [ "PROVIDE primary trial plus voluntary open-label extension; not independent clinical replication" ] }, { "n": 24, "pmid": "40926079", "title": "Resistance training, but not leucine, increased basal muscle protein synthesis and reversed frailty in older women consuming optimized protein intake.", "citation": "Jacob KJ, Hajj-Boutros G, Sonjak V et al. Resistance training, but not leucine, increased basal muscle protein synthesis and reversed frailty in older women consuming optimized protein intake. GeroScience. 2026.", "doi": "10.1007/s11357-025-01877-2", "pmcid": "PMC13356255", "url": "https://pubmed.ncbi.nlm.nih.gov/40926079/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40926079/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID40926079", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "null", "what_it_shows": "19 pre/frail women with 1.2 g/kg and training have no added leucine MPS/strength/frailty benefit", "what_it_does_not_show": "Small study; training plus adequate diet benefits do not quantify 0.8 comparison", "confounders_present": [ "Small study; training plus adequate diet benefits do not quantify 0.8 comparison" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 25, "pmid": "41690799", "title": "Impact of an exercise and nutrition program on caregiver time with residents in institutional care-A secondary analysis.", "citation": "Wimo A, Cederholm T, Irving GF et al. Impact of an exercise and nutrition program on caregiver time with residents in institutional care-A secondary analysis. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2026.", "doi": "10.1002/alz.71198", "pmcid": "PMC12906372", "url": "https://pubmed.ncbi.nlm.nih.gov/41690799/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41690799/", "tier": "A", "source_tier": "A", "kind": "secondary_analysis", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "OPEN_NCT02702037", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "OPEN secondary analysis finds less caregiver time in dementia but not somatic units with combined program", "what_it_does_not_show": "Same OPEN cohort as 32471657; cluster/design and resource endpoint; not isolated protein strength effect", "confounders_present": [ "Same OPEN cohort as 32471657; cluster/design and resource endpoint; not isolated protein strength effect" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [ "same OPEN102-completer cohort as 32471657" ] }, { "n": 26, "pmid": "29252150", "title": "Whey Protein Supplementation Improves Rehabilitation Outcomes in Hospitalized Geriatric Patients: A Double Blinded, Randomized Controlled Trial.", "citation": "Niccoli S, Kolobov A, Bon T et al. Whey Protein Supplementation Improves Rehabilitation Outcomes in Hospitalized Geriatric Patients: A Double Blinded, Randomized Controlled Trial. Journal of nutrition in gerontology and geriatrics. 2017.", "doi": "10.1080/21551197.2017.1391732", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/29252150/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29252150/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID29252150", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "47 hospitalized elders randomized whey report better grip and knee extensor recovery", "what_it_does_not_show": "Hospital duration not fixed 8–52 weeks; rehab context baseline under feeding and achieved above RDA not reported abstract", "confounders_present": [ "Hospital duration not fixed 8–52 weeks; rehab context baseline under feeding and achieved above RDA not reported abstract" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 27, "pmid": "41632571", "title": "A multicomponent intervention consisting of exercise, proteins and omega-3 supplementation to improve sarcopenia in community-dwelling older adults: Lessons learned from a 5-armed randomized controlled feasibility trial.", "citation": "Amini N, Dupont J, Lapauw L et al. A multicomponent intervention consisting of exercise, proteins and omega-3 supplementation to improve sarcopenia in community-dwelling older adults: Lessons learned from a 5-armed randomized controlled feasibility trial. The Journal of frailty & aging. 2026.", "doi": "10.1016/j.tjfa.2025.100129", "pmcid": "PMC12887399", "url": "https://pubmed.ncbi.nlm.nih.gov/41632571/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41632571/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41632571", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "58-person ENHANce five arm feasibility trial supplies exploratory functional signals and adherence problems", "what_it_does_not_show": "Small arms 9–13 participants and low recruitment; not powered clinical component proof", "confounders_present": [ "Small arms 9–13 participants and low recruitment; not powered clinical component proof" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 28, "pmid": "31734121", "title": "Effect of Protein Supplementation on Physical Performance in Older People With Sarcopenia-A Randomized Controlled Trial.", "citation": "Björkman MP, Suominen MH, Kautiainen H et al. Effect of Protein Supplementation on Physical Performance in Older People With Sarcopenia-A Randomized Controlled Trial. Journal of the American Medical Directors Association. 2020.", "doi": "10.1016/j.jamda.2019.09.006", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/31734121/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31734121/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID31734121", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "null", "what_it_shows": "218 older sarcopenic adults 12-month whey trial finds no functional, grip or mass benefit or post-trial survival difference", "what_it_does_not_show": "Home-exercise advice and gastrointestinal burden; baseline context not all underfed frailty", "confounders_present": [ "Home-exercise advice and gastrointestinal burden; baseline context not all underfed frailty" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 29, "pmid": "30921603", "title": "Effects of whey protein nutritional supplement on muscle function among community-dwelling frail older people: A multicenter study in China.", "citation": "Kang L, Gao Y, Liu X et al. Effects of whey protein nutritional supplement on muscle function among community-dwelling frail older people: A multicenter study in China. Archives of gerontology and geriatrics. 2019.", "doi": "10.1016/j.archger.2019.03.012", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30921603/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30921603/", "tier": "A", "source_tier": "A", "kind": "case_control", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID30921603", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Weak", "system": "human observational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Chinese 115-person frailty study reports between-group whey/training functional differences", "what_it_does_not_show": "PubMed-indexed RCT but original abstract describes case-control; do not assume randomization; self-selection/confounding", "confounders_present": [ "PubMed-indexed RCT but original abstract describes case-control; do not assume randomization; self-selection/confounding" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": false, "decisive_test_note": "", "shared_components": [] }, { "n": 30, "pmid": "41805014", "title": "Fermented Whey Protein Supplement Slows the Progression of Frailty and Sarcopenia Among Older Korean Adults: A Randomized Blinded Trial.", "citation": "Lim HS, Jung DH, Kim HY et al. Fermented Whey Protein Supplement Slows the Progression of Frailty and Sarcopenia Among Older Korean Adults: A Randomized Blinded Trial. Journal of medicinal food. 2026.", "doi": "10.1177/1096620X261430172", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/41805014/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/41805014/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41805014", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "45 older Korean adults 10-week fermented whey trial reports eSPPB between-arm improvement", "what_it_does_not_show": "Nutrition profile vitamin D/calcium/magnesium changes with protein; small sample; no isolated above RDA proof", "confounders_present": [ "Nutrition profile vitamin D/calcium/magnesium changes with protein; small sample; no isolated above RDA proof" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 31, "pmid": "31672329", "title": "From mitochondria to healthy aging: The role of branched-chain amino acids treatment: MATeR a randomized study.", "citation": "Buondonno I, Sassi F, Carignano G et al. From mitochondria to healthy aging: The role of branched-chain amino acids treatment: MATeR a randomized study. Clinical nutrition (Edinburgh, Scotland). 2020.", "doi": "10.1016/j.clnu.2019.10.013", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/31672329/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31672329/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID31672329", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Specialized High-Protein Oral Nutrition Supplement Improves Home Nutrient Intake of Malnourished Older Adults Without Decreasing Usual Food Intake. JPEN. Journal of parenteral and enteral nutrition. 2019.", "doi": "10.1002/jpen.1467", "pmcid": "PMC6924274", "url": "https://pubmed.ncbi.nlm.nih.gov/30565718/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30565718/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID30565718", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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A 16-week randomized controlled trial of a fish oil and whey protein-derived supplement to improve physical performance in older adults losing autonomy-A pilot study. PloS one. 2021.", "doi": "10.1371/journal.pone.0256386", "pmcid": "PMC8382183", "url": "https://pubmed.ncbi.nlm.nih.gov/34424934/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34424934/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID34424934", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in healthy older versus younger men. The journals of gerontology. Series A, Biological sciences and medical sciences. 2015.", "doi": "10.1093/gerona/glu103", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/25056502/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25056502/", "tier": "A", "source_tier": "A", "kind": "secondary_analysis", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Pooled_original_MPS_data_parent_overlap_unresolved", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Protein Requirements of Elderly Chinese Adults Are Higher than Current Recommendations. The Journal of nutrition. 2020.", "doi": "10.1093/jn/nxaa031", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/32140711/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32140711/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID32140711", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Dietary protein intake in sarcopenic obese older women. Clinical interventions in aging. 2016.", "doi": "10.2147/CIA.S96017", "pmcid": "PMC4751896", "url": "https://pubmed.ncbi.nlm.nih.gov/26917955/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26917955/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID26917955", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Protein supplementation during resistance-type exercise training in the elderly. Medicine and science in sports and exercise. 2013.", "doi": "10.1249/MSS.0b013e318272fcdb", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/22968306/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/22968306/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID22968306", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Synergistic effect of bodyweight resistance exercise and protein supplementation on skeletal muscle in sarcopenic or dynapenic older adults. Geriatrics & gerontology international. 2019.", "doi": "10.1111/ggi.13643", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30864254/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30864254/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID30864254", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Protein anabolic responses to a fed steady state in healthy aging. The journals of gerontology. Series A, Biological sciences and medical sciences. 2011.", "doi": "10.1093/gerona/glr036", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/21436253/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/21436253/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID21436253", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Protein intake protects against weight loss in healthy community-dwelling older adults. The Journal of nutrition. 2014.", "doi": "10.3945/jn.113.184705", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/24357473/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24357473/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID24357473", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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Effect of Protein Intake on Lean Body Mass in Functionally Limited Older Men: A Randomized Clinical Trial. JAMA internal medicine. 2018.", "doi": "10.1001/jamainternmed.2018.0008", "pmcid": "PMC5885156", "url": "https://pubmed.ncbi.nlm.nih.gov/29532075/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29532075/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID29532075", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: PMC5885156 Methods:Participants/Interventions/Exercise/Outcomes; web lines331-367, PMC5885156 Results:Compliance/LeanBodyMass/PhysicalFunction; web lines459-498. 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Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trial. Journal of the American Medical Directors Association. 2012.", "doi": "10.1016/j.jamda.2012.07.005", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/22889730/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/22889730/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Tieland_nutritiononly_NCT01109628", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [ "M1", "M3" ], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": true, "endogenous": true, "direction": "mixed", "what_it_shows": "Frail 65-person 24-week protein only trial reports SPPB improvement without muscle mass increase", "what_it_does_not_show": "Leg extension between-arm trend not conventional significance; actual total dose not verified original abstract; not universal benefit", "confounders_present": [ "Leg extension between-arm trend not conventional significance; actual total dose not verified original abstract; not universal benefit" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] }, { "n": 55, "pmid": "25646324", "title": "A high whey protein-, leucine-, and vitamin D-enriched supplement preserves muscle mass during intentional weight loss in obese older adults: a double-blind randomized controlled trial.", "citation": "Verreijen AM, Verlaan S, Engberink MF et al. A high whey protein-, leucine-, and vitamin D-enriched supplement preserves muscle mass during intentional weight loss in obese older adults: a double-blind randomized controlled trial. The American journal of clinical nutrition. 2015.", "doi": "10.3945/ajcn.114.090290", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/25646324/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25646324/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID25646324", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2", "SC3", "SC4" ], "favors_models": [ "M4" ], "evidence_class": "Strong", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "mixed", "what_it_shows": "Obese older adult weight loss RCT with matched RT shows enriched protein preserves appendicular lean mass but not strength/function", "what_it_does_not_show": "Whey/leucine/vit D mixture; actual 1.11 vs 0.85 g/kg; lean mass benefit not functional efficacy", "confounders_present": [ "Whey/leucine/vit D mixture; actual 1.11 vs 0.85 g/kg; lean mass benefit not functional efficacy" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "", "shared_components": [] }, { "n": 56, "pmid": "22770932", "title": "Protein supplementation increases muscle mass gain during prolonged resistance-type exercise training in frail elderly people: a randomized, double-blind, placebo-controlled trial.", "citation": "Tieland M, Dirks ML, van der Zwaluw N et al. Protein supplementation increases muscle mass gain during prolonged resistance-type exercise training in frail elderly people: a randomized, double-blind, placebo-controlled trial. Journal of the American Medical Directors Association. 2012.", "doi": "10.1016/j.jamda.2012.05.020", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/22770932/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/22770932/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Tieland_training_NCT01110369", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. 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The cost effectiveness of personalized dietary advice to increase protein intake in older adults with lower habitual protein intake: a randomized controlled trial. European journal of nutrition. 2021.", "doi": "10.1007/s00394-021-02675-0", "pmcid": "PMC8490609", "url": "https://pubmed.ncbi.nlm.nih.gov/34609621/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34609621/", "tier": "A", "source_tier": "A", "kind": "rct", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-11-02", "status_checked_on": "2026-11-02", "study_id": "PMID34609621", "access_depth": "full_text_partial", "access_note": "Original PMC full body text (PMC8490609) retrieved through PubMed Central on 2026-11-02 and read: Methods (design, intervention, outcomes, sample size, statistical and sensitivity analyses), Results (compliance, 400-m walk, secondary outcomes, sensitivity analyses) and Discussion limitations; tables, figures and supplements not examined. Main result also stated in the secondary report PMID 37347495 (abstract). Added after round-3 adversarial review.", "relates_to_subclaims": [ "SC3", "SC4" ], "favors_models": [ "M1" ], "evidence_class": "Moderate", "system": "human interventional", "decisive_perturbation": false, "endogenous": true, "direction": "supports", "what_it_shows": "276 community-dwelling adults aged 65 or over with habitual intake below 1.0 g/kg adjusted body weight/day: six months of dietary advice plus protein-enriched foods targeting at least 1.2 g/kg/day improved the primary 400-m walk time versus no advice (-12.4 s, 95% CI -21.8 to -2.9) and leg-extension strength (+32.6 N, 95% CI 10.6 to 54.5)", "what_it_does_not_show": "Open-label; control received no advice; energy intake rose 107 kcal/day; only 37.5% reached the target and the per-protocol walk-time effect was not significant; advice-plus-timing arm -4.9 s with CI crossing zero; secondary outcomes exploratory; non-malnourished population and not an isolated protein-quantity contrast", "confounders_present": [ "Open-label; control received no advice; energy intake rose 107 kcal/day; only 37.5% reached the target and the per-protocol walk-time effect was not significant; advice-plus-timing arm -4.9 s with CI crossing zero; secondary outcomes exploratory; non-malnourished population and not an isolated protein-quantity contrast" ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism. Added 2026-11-02 after round-3 adversarial review (finding P1).", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "discriminating_contrast": true, "decisive_test_note": "Pivotal test, including null or negative results and restricted contexts; this flag is not a positive threshold crossing.", "shared_components": [] } ], "verification_summary": { "load_bearing_claims_checked": 62, "verified": 62, "unverified": 0, "contradicted": 0, "note": "Verified attribution is distinct from mechanism truth or complete body access." }, "factual_issues_found": [], "cap_rules_applied": [ { "subclaim_id": "SC1", "cap": "Γ", "cap_source": "universal", "triggered": true, "trigger_text_quoted": "Biomarker change without functional/phenotypic change caps at Γ.", "specific_trigger": "Controlled feeding and tracer studies show acute anabolic responses that vary by dose, composition, activity and health. MPS or nitrogen-turnover movement alone does not demonstrate sustained muscle accretion or functional benefit, and nutrient-sensing mediation is not isolated. The functional inference from acute synthesis evidence is held at Γ under the biomarker-only cap.", "resulting_ceiling": "Γ" } ], "cap_precedence_resolutions": [ { "collision": "Perturbation in a defined setting versus broader inference", "subclaim_scope_cap_binds_on": "Increasing dietary protein intake above the adult recommended allowance improves muscle strength or physical function in adults aged 60 years or older.", "subclaim_scope_threshold_binds_on": "The precise experimentally tested subclaim scope", "resolution": "Controlled human gait/strength outcomes cross the adapted clinical threshold for the precise baseline nutrition and dose context tested. Acute MPS and peripheral markers remain biomarker-limited evidence, and body composition surrogates do not replace function. Short rehabilitation, mixed age and multi-ingredient/combined training exposures retain their own scope; no effect attributed to an entire package is silently reassigned to protein alone.", "note": "Convergent lines are assessed as a set; one weak leg is not re-capped over the assembled case." } ], "boundary_check_BGD": [ { "subclaim_id": "SC1", "field_valid_perturbation_quote": "\n- Genetic or pharmacologic intervention producing reproducible lifespan/healthspan extension\n- Must separate developmental effects from true aging effects\n- Biomarker change alone does NOT satisfy this threshold", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "Biomarker-only improvement without organismal benefit" ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Controlled feeding and tracer studies show acute anabolic responses that vary by dose, composition, activity and health. MPS or nitrogen-turnover movement alone does not demonstrate sustained muscle accretion or functional benefit, and nutrient-sensing mediation is not isolated. The functional inference from acute synthesis evidence is held at Γ under the biomarker-only cap.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC2", "field_valid_perturbation_quote": "\n- Genetic or pharmacologic intervention producing reproducible lifespan/healthspan extension\n- Must separate developmental effects from true aging effects\n- Biomarker change alone does NOT satisfy this threshold", "qualifying_evidence_present": "yes", "qualifying_evidence_citation": "PMID 30475969", "gamma_hard_rules_triggered": [ "Imaging/proxy measurements have explicit limits; positive same-scope paired nutrition/functional results are retained, not generalized to all muscle sites or mechanisms." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "yes", "perturbation_result_note": "Controlled older-adult nutrition studies retain positive mass/lean-tissue findings in predefined malnourished, sarcopenic or energy-deficit contexts. Other controlled trials find no mass benefit despite higher intake; DXA/BIA lean tissue is not equivalent to anatomical muscle or strength. Context-specific preservation is Ε, with source-specific body composition limits and no inference that every higher protein protocol increases muscle.", "ceiling_from_boundary_check": "Δ or higher" }, { "subclaim_id": "SC3", "field_valid_perturbation_quote": "\n- Genetic or pharmacologic intervention producing reproducible lifespan/healthspan extension\n- Must separate developmental effects from true aging effects\n- Biomarker change alone does NOT satisfy this threshold", "qualifying_evidence_present": "yes", "qualifying_evidence_citation": "PMID 30475969", "gamma_hard_rules_triggered": [ "Measured gait/strength/function outcomes prevent a biomarker-only restriction for the primary positive context; negative trials do not earn positive crossings." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "yes", "perturbation_result_note": "A quantified 0.8/1.2/1.5 g/kg trial in baseline malnourished pre-frail or frail elders shows a modest gait benefit at 1.5 g/kg over 12 weeks, with the intermediate arm null. A frail protein-only 24-week trial also reports SPPB benefit while mass is unchanged, though its exact total dose is not verified in the original abstract. Controlled 0.8 vs 1.3 g/kg feeding in stable function-limited men and one-year sarcopenia trials are null. An open-label six-month advice-plus-protein-enriched-foods trial in non-malnourished community-dwelling adults with habitual intake below 1.0 g/kg adjusted body weight/day also reports a primary 400-m walk benefit, with energy intake co-increased and the per-protocol effect not significant. These map context-specific human functional causality at Ε; multi-ingredient/RT package successes cannot supply a universal protein effect.", "ceiling_from_boundary_check": "Δ or higher" }, { "subclaim_id": "SC4", "field_valid_perturbation_quote": "\n- Genetic or pharmacologic intervention producing reproducible lifespan/healthspan extension\n- Must separate developmental effects from true aging effects\n- Biomarker change alone does NOT satisfy this threshold", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "", "gamma_hard_rules_triggered": [ "No quantified positive cross-context or medication-specific functional crossing was verified; a protein physiology narrative cannot replace generalization." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "General efficacy across adequate intake, frailty and medication-assisted weight loss without training is not established. Predefined nutrition, training, formulation and energy balance modify outcomes; some frail cohorts are null. The GLP-1 lean-mass protection claim needs direct protein/training results rather than DXA loss narratives. Partial physiological plausibility remains Γ, not a validated generalization rule or a blanket claim that every older person needs the same high dose.", "ceiling_from_boundary_check": "Γ" } ], "thresholds_tested": [ { "subclaim_id": "SC1", "threshold": "Δ", "requirement_quoted": "Requires at least one intervention changing lifespan or healthspan in a way consistent with the hypothesis.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Pair sustained protein quantity exposure and integrated MPS/turnover with imaging and prespecified strength/function; demonstrate a mediation or dissociation test rather than declaring the acute rate increase sufficient." }, { "subclaim_id": "SC2", "threshold": "Δ", "requirement_quoted": "Requires at least one intervention changing lifespan or healthspan in a way consistent with the hypothesis.", "satisfied": "yes", "supporting_evidence": [ "[22] 120 malnourished pre-frail or frail elders randomized 0.8/1.2/1.5 g/kg for 12 weeks show 1.5-arm mass/gait improvement" ], "what_would_cross_it": "" }, { "subclaim_id": "SC2", "threshold": "Ε", "requirement_quoted": "Requires causal effect in constrained contexts, backgrounds, or species.", "satisfied": "yes", "supporting_evidence": [ "[22] 120 malnourished pre-frail or frail elders randomized 0.8/1.2/1.5 g/kg for 12 weeks show 1.5-arm mass/gait improvement" ], "what_would_cross_it": "" }, { "subclaim_id": "SC2", "threshold": "Ζ", "requirement_quoted": "Requires:\n- Reproducible intervention effects\n- Mechanistic narrowing\n- Evidence not reducible to general sickness, caloric reduction, or developmental artifacts", "satisfied": "no", "supporting_evidence": [ "[22] 120 malnourished pre-frail or frail elders randomized 0.8/1.2/1.5 g/kg for 12 weeks show 1.5-arm mass/gait improvement" ], "what_would_cross_it": "Replicate sustained anatomical muscle preservation with absolute baseline and achieved intake, matched energy, hydration controls and relevant exercise strata, rather than equating every DXA/BIA change with muscle gain." }, { "subclaim_id": "SC3", "threshold": "Δ", "requirement_quoted": "Requires at least one intervention changing lifespan or healthspan in a way consistent with the hypothesis.", "satisfied": "yes", "supporting_evidence": [ "[22] 120 malnourished pre-frail or frail elders randomized 0.8/1.2/1.5 g/kg for 12 weeks show 1.5-arm mass/gait improvement" ], "what_would_cross_it": "" }, { "subclaim_id": "SC3", "threshold": "Ε", "requirement_quoted": "Requires causal effect in constrained contexts, backgrounds, or species.", "satisfied": "yes", "supporting_evidence": [ "[22] 120 malnourished pre-frail or frail elders randomized 0.8/1.2/1.5 g/kg for 12 weeks show 1.5-arm mass/gait improvement" ], "what_would_cross_it": "" }, { "subclaim_id": "SC3", "threshold": "Ζ", "requirement_quoted": "Requires:\n- Reproducible intervention effects\n- Mechanistic narrowing\n- Evidence not reducible to general sickness, caloric reduction, or developmental artifacts", "satisfied": "no", "supporting_evidence": [ "[22] 120 malnourished pre-frail or frail elders randomized 0.8/1.2/1.5 g/kg for 12 weeks show 1.5-arm mass/gait improvement" ], "what_would_cross_it": "Run an adequately powered independently replicated isocaloric 0.8-versus-higher protein trial in prespecified frail/malnourished and adequately nourished adults with functional primary endpoints, matched co-ingredients and factorial training." }, { "subclaim_id": "SC4", "threshold": "Δ", "requirement_quoted": "Requires at least one intervention changing lifespan or healthspan in a way consistent with the hypothesis.", "satisfied": "no", "supporting_evidence": [], "what_would_cross_it": "Test baseline intake/frailty/renal status and medication-assisted weight loss prospectively with direct dose separation, factorial exercise and clinically meaningful function, not post-outcome responder narrowing." } ], "generalization_check": { "generalization_tested": "yes", "context_boundary_mapped": "yes", "internal_negative_controls": [ "PMID 30475969:1.2 g/kg arm not better than 0.8 while 1.5 g/kg has selected mass/gait benefit.", "PMID 29532075:direct energy controlled 0.8 vs 1.3 g/kg six-month functional/mass null.", "PMID 33564844:protein-only null but loading contrasts positive.", "PMID 25646324:appendicular lean mass preserved without between-arm strength/function effect.", "PMID 31734121:12-month sarcopenia whey null, showing frailty/sarcopenia alone is not a sufficient beneficiary definition.", "PMID 32471657:main functional null despite positive post-randomization adherence subgroup." ], "note": "Age ≥60, baseline intake, validated malnutrition/frailty, energy deficit, achieved protein separation, exercise, formulation and renal state are assessed before outcomes. Positive malnourished-dose and null stable feeding/training/sarcopenia contexts map a heterogeneous boundary. Frail participants with null outcomes remain in scope; a responder-defined nutritional deficit is forbidden. Mixed 50–79-year reports and sub-8-week rehab are boundary evidence rather than a clean primary 8–52-week ≥60 clinical crossing." }, "falsification_patterns_met": [], "pitfalls_flagged": [ { "pitfall": "Confirmation by biomarker", "where": "MPS, nitrogen balance, creatinine and DXA/BIA proxies are distinct from clinical strength/function." }, { "pitfall": "Therapeutic effect misread as mechanistic proof", "where": "Multi-ingredient or training-package benefit does not isolate protein quantity or MPS mediation." }, { "pitfall": "Scope fitted to the result", "where": "OPEN post-randomization adherence and retrospective responder groups cannot define who needs protein." }, { "pitfall": "Negative field-valid perturbation read as a crossed threshold", "where": "OPTIMen/CALM/sarcopenia nulls are discriminators, not positive crossings." }, { "pitfall": "Replication confused with reproduction", "where": "PROVIDE/OPEN secondary reports and pooled tracers are grouped by study; total reference count does not measure independent causal lines." } ], "causal_tally_audit": { "tally_claimed_by_document": 1, "tally_after_audit": 1, "tally_unit": "Positive qualifying study units across scoped subclaims, not independent causal lines or full-claim necessity/sufficiency.", "screened_discriminating_contrasts": 24, "items_rejected": [ "Null and negative contrasts are discriminators, not positive threshold crossings. Reports and replications are not independent causal lines.", "Only positive same-scope protein quantity-functional contrasts earn primary crossing credit; multi-ingredient packages cannot manufacture pure protein effects.", "Acute MPS/IAAO, short bed rest, mixed age, sub-8-week rehab and >52-week follow-up support boundaries not the exact primary clinical horizon.", "Corrected collagen result remains bounded and not a load-bearing clinical crossing until notice contents and protein exposure attribution are clear.", "One parent study can produce legitimate secondary reports without adding an independent causal line." ] }, "steelman": { "case_one_rung_higher": "Case for Ζ: many randomized human nutrition studies report mass/grip/gait improvements, acute tracers show biological activity, and loading/protein factorial studies supply additional causal controls. This is stronger than a generic supplement story and includes real functionally relevant positive results.", "case_one_rung_lower": "Case for Δ: the clean above-RDA clinical dose positive rests heavily on one malnourished frail trial with secondary gait outcome, whereas large/long stable feeding and sarcopenia trials are null. Ingredient mixtures, inadequate dose separation and shared parent reports make the apparent replication volume much less direct than the bibliography suggests.", "which_rejected": "Ζ is rejected because nutrition RCT replication is one modality and mixed ingredient/tracer/loading experiments do not supply independent same-scope positive protein-function lines. Δ would under state the prospectively defined nutritional/dose boundary and positive-versus-null controlled context mapping;Ε retains restricted benefit without claiming a validated uniform response rule.", "blocking_cap_threshold_or_missing_experiment": "Missing experiment: A preregistered multicenter isocaloric protein quantity trial with 0.8 g/kg/day comparator and clearly achieved higher intake, stratified before outcomes by nutrition/frailty and including a factorial resistance-training component; GLP-1 treated adults need their own controlled stratum with measured function." }, "final_score": { "hsef_level": "Ε", "hsef_descriptor": "Context-specific causality established", "confidence": "Moderate", "confidence_rationale": "Moderate reflects evidence density and reproducibility, not correctness and not this reviewer's access depth. The clinical trials are numerous and independent but heterogeneous in formulation, achieved intake, comparator and endpoint, and the positive and null results do not reproduce across baseline contexts. Access depth is recorded separately in the provenance header and is not a basis for the band.", "rests_on_non_peer_reviewed_work": false, "rationale": "The registered primary-subclaim rule selects SC3. A quantified above-RDA protein contrast produced a modest functional benefit in a baseline malnourished, pre-frail or frail population. Controlled feeding and supplementation nulls in other defined populations limit generalization, supporting Ε with Moderate confidence. Acute synthesis and lean mass do not establish universal strength preservation. Weakest-link returns Γ; primary-subclaim and scope-matched return Ε. An open-label six-month dietary-advice trial (PROMISS, PMID 34609621) in non-malnourished community-dwelling adults with near-allowance habitual intake also improved its primary 400-m walk outcome, but it co-increased energy intake and lost significance per protocol, while OPTIMen was null at similar baseline intake, so reproducible intervention effects for Ζ are still not met." }, "role_of_mechanism": { "classification": "reinforcing / stabilizing factor", "derivation_step_matched": 5, "derivation": "Above-RDA intake precedes selected functional gains in nutritionally vulnerable settings, so the intervention is not mere co-occurrence. Necessity of above-RDA intake for all older-adult strength, initiation and rate limitation are not established, and normal protein need must not be conflated with necessity of additional supplementation. Step 5 identifies a reinforcing/stabilizing input within a system also determined by loading, energy, health and neuromuscular adaptation.", "tournament_used_as_tiebreaker": false, "note": "Derived from causal direction, not tournament rank." }, "extended_scoring_MSD": { "momentum": { "value": "Mechanistic only", "artifact": "No examined work could cross the next threshold for the registered claim. The registered 2026 LEAN-PREP protocol PMID 42020128 is live work - it explicitly plans protein and resistance training during semaglutide/tirzepatide treatment, and no result from it is claimed - but it tests the medication-assisted weight-loss boundary that SC4 scopes, and under the pre-registered primary-subclaim rule a result there cannot move SC3, which sets the headline. Running is necessary but not sufficient; both halves of the definition must hold. Lead adjudication 2026-10-14. The recent factorial-target and nutrition-only reports PMID 42735207 and PMID 41805014 are completed, published trials and are evidence in the ledger, not momentum.", "justification": "No examined work could cross the next threshold for the registered claim. The registered 2026 LEAN-PREP protocol PMID 42020128 is live work - it explicitly plans protein and resistance training during semaglutide/tirzepatide treatment, and no result from it is claimed - but it tests the medication-assisted weight-loss boundary that SC4 scopes, and under the pre-registered primary-subclaim rule a result there cannot move SC3, which sets the headline. Running is necessary but not sufficient; both halves of the definition must hold. Lead adjudication 2026-10-14. The recent factorial-target and nutrition-only reports PMID 42735207 and PMID 41805014 are completed, published trials and are evidence in the ledger, not momentum.", "prior_value_before_lead_adjudication": "Decisive work underway", "lead_adjudication": "2026-10-14: \"Decisive work underway\" requires work being run that could cross the next threshold of the REGISTERED claim. LEAN-PREP tests the SC4 boundary and cannot move SC3, which sets the headline, so the value is Mechanistic only. Momentum modifies no letter." }, "stability": { "value": "Stable", "trigger": "No named pending result could move the registered claim's letter. Completed LEAN-PREP functional and body-composition results could clarify the medication-assisted weight-loss context - precise functional nulls would narrow that application while positive controlled component effects could extend it - and no result from the protocol is claimed; but that trigger is scoped to that application and to SC4, not to the registered SC3 letter, and under the pre-registered primary-subclaim rule a result there cannot move the score. It is the only named pending result in this review: every trial registry identifier cited belongs to a completed, published study already in the ledger, and the knowledge gaps and boundary experiment name work that is needed but not under way. Where no trigger that could move the score can be named, the answer is Stable by definition.", "justification": "No named pending result could move the registered claim's letter. Completed LEAN-PREP functional and body-composition results could clarify the medication-assisted weight-loss context - precise functional nulls would narrow that application while positive controlled component effects could extend it - and no result from the protocol is claimed; but that trigger is scoped to that application and to SC4, not to the registered SC3 letter, and under the pre-registered primary-subclaim rule a result there cannot move the score. It is the only named pending result in this review: every trial registry identifier cited belongs to a completed, published study already in the ledger, and the knowledge gaps and boundary experiment name work that is needed but not under way. Where no trigger that could move the score can be named, the answer is Stable by definition.", "prior_value_before_lead_adjudication": "Uncertain", "lead_adjudication": "2026-10-14: Stability asks what would move THE SCORE. LEAN-PREP addresses SC4 and cannot move SC3, which sets the letter, so it is not a Stability trigger. Applied conditionally on LEAN-PREP being the sole named trigger, which was verified. Stable by definition. M/S/D modify neither level nor confidence.", "sole_named_trigger_verification": "The two directions in the original text are both consequences of LEAN-PREP itself; all five registry identifiers in the review (NCT01109628, NCT01110369, NCT01890382, NCT02702037, NTR2323) belong to completed published studies in the ledger; the knowledge gaps and boundary experiment name needed-but-unrun work, which is not a trigger." }, "divergence": { "implied_level": null, "implied_level_basis": "No single field-implied level is defensible from conflicting framings.", "assessed_level": "Ε", "gap_in_rungs": null, "value": "Contested", "justification": "No manufactured field consensus or arithmetic gap." }, "calibration_note": "M/S/D never modify HSEF level or confidence." }, "change_record": { "applies": false, "prior_level": "none assigned", "prior_confidence": null, "prior_source": null, "derived_before_consulting_prior": true, "new_level": "Ε", "direction": "newly assigned", "what_moved_it": "Fresh primary evidence appraisal; not blinded.", "divergence_from_other_reviewers": null }, "proposed_decisive_experiments": [ { "name": "Registered boundary experiment", "experiment": "A preregistered multicenter isocaloric protein quantity trial with 0.8 g/kg/day comparator and clearly achieved higher intake, stratified before outcomes by nutrition/frailty and including a factorial resistance-training component; GLP-1 treated adults need their own controlled stratum with measured function.", "readout": "Functional primary endpoint such as SPPB, gait or chair rise and prespecified strength at fixed 12–52-week horizon, plus anatomical muscle imaging and DXA/BIA reported separately", "critical_control": "Matched calories, micronutrients/ingredients, counseling, exercise intensity and contact; achieved total protein verified; participant-level ITT with cluster handling and multiplicity; no outcome/adherence-defined beneficiary scope", "supporting_result": "Replicated clinically interpretable functional benefit attributable to protein quantity with baseline-defined interaction and adequate intake separation", "falsifying_result": "Precise functional null despite achieved protein contrast, or package benefit confined to training/micronutrients while protein-only is null" } ], "knowledge_gaps": [ { "name": "Gap 1", "statement": "A universal above-RDA target cannot be read from an acute MPS plateau or observational diet association.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 2", "statement": "The relative contribution of protein quantity, quality, energy correction, vitamin D and exercise needs matched component controls.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 3", "statement": "Long-term muscle function is not identical to DXA/BIA lean mass or biochemical anabolism.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 4", "statement": "Achieved intake and baseline frailty/nutrition interactions need independent prospective replication; frailty alone is not a responder definition.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 5", "statement": "Medication-assisted weight loss protein/training evidence is still directly needed; protocols do not validate all GLP-1 muscle-loss mitigation claims.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 6", "statement": "Renal state, exposure duration and product ingredients define safety inference; short unchanged creatinine is not all-population safety proof.", "relevance": "Limits mechanism identification or scope." } ], "review_metadata": { "review_date": "2026-10-12", "reviewer": "Codex", "evidence_base_note": "57 primary reports (56 at original sealing; PROMISS, PMID 34609621, added 2026-11-02 after round-3 adversarial review); literature cutoff 2026-10-12; source examination UTC date 2026-10-13; bounded critical review, not exhaustive systematic review.", "literature_tools_available": true, "literature_tools_note": "Life Sciences Literature PubMed/Entrez, separately logged public original-body retrieval, and Consensus Pro browser searches. Provider output retained as observed browser text with citation-link mappings, or as previously exported connector documents where present. AI synthesis is not primary full-text verification. Consensus retrieved/included counts are not examined-primary counts. Scite monthly limit was reached earlier in this session; no new Scite query or incoming citation-context audit is claimed for these cases. Tool receipts record actual use. Supplementary discovery outputs do not earn primary-count credit. No independent blinded review.", "skill_version": "5.3", "validator_run": "PASS: exact archived HSEF v5.3 validator rerun after final sealing.", "validator_warnings_addressed": "No warnings.", "limits": "Bounded source-based critical review; no complete-paper/supplement audit, independent scientific peer review or blinded calibration. Revision cases retain original prose outside the three framework output blocks and have explicit correction logs.", "adversarial_review": { "round": 3, "adversarial_reviewer": "Claude Opus 5.5 (Anthropic)", "date": "2026-11-02", "findings_applied": [ "P1", "P2", "P3", "P4", "P5", "P6", "P7" ], "findings_not_applied": [], "level_after": "Ε", "confidence_after": "Moderate", "records": [ "ADVERSARIAL_REVIEW.protein-muscle-aging.md", "adversarial-findings.protein-muscle-aging.json" ], "prior_round": "Round 2, Claude Opus 5.5 (Anthropic), 2026-10-14, findings B-1 to B-6 (recorded in the review's ADVERSARIAL REVIEW AND APPROVAL section)" } }, "is_calibration_entry": { "value": false, "entry_role": "not_calibration", "blind_graded": null, "completed_blinded_calibration": false, "expected_band_sealed_at": "", "target_sha256": "", "target_authorship": "not applicable", "target_author_saw_review": null, "future_run_status": "not prepared", "unblinded_reason": "These topic families were selected from an editorial traffic-priority list. Selection was visible; no blind calibration or predetermined clinical verdict was preregistered." }, "upper_ladder_check": { "final_level_below_zeta": true, "equivalents_considered": [ { "kind": "mendelian_randomization", "available": false, "why_not_sufficient": "Direct graded intake, factorial training, bed rest/de-training, tracer physiology and population diet studies were considered. They answer different endpoints/scopes. Replicated oral nutrition trials remain one clinical modality, observational diet cannot fix confounding, and MPS is not an orthogonal functional causal line. No validated baseline prediction, isolated nutrient mechanism or cross-context necessity/sufficiency supports Ζ or higher for the registered above-RDA function claim." }, { "kind": "natural_experiment", "available": false, "why_not_sufficient": "Direct graded intake, factorial training, bed rest/de-training, tracer physiology and population diet studies were considered. They answer different endpoints/scopes. Replicated oral nutrition trials remain one clinical modality, observational diet cannot fix confounding, and MPS is not an orthogonal functional causal line. No validated baseline prediction, isolated nutrient mechanism or cross-context necessity/sufficiency supports Ζ or higher for the registered above-RDA function claim." }, { "kind": "dose_response_across_populations", "available": false, "why_not_sufficient": "Direct graded intake, factorial training, bed rest/de-training, tracer physiology and population diet studies were considered. They answer different endpoints/scopes. Replicated oral nutrition trials remain one clinical modality, observational diet cannot fix confounding, and MPS is not an orthogonal functional causal line. No validated baseline prediction, isolated nutrient mechanism or cross-context necessity/sufficiency supports Ζ or higher for the registered above-RDA function claim." }, { "kind": "withdrawal_rechallenge", "available": true, "why_not_sufficient": "Direct graded intake, factorial training, bed rest/de-training, tracer physiology and population diet studies were considered. They answer different endpoints/scopes. Replicated oral nutrition trials remain one clinical modality, observational diet cannot fix confounding, and MPS is not an orthogonal functional causal line. No validated baseline prediction, isolated nutrient mechanism or cross-context necessity/sufficiency supports Ζ or higher for the registered above-RDA function claim." }, { "kind": "therapeutic_perturbation_hard_endpoint", "available": false, "why_not_sufficient": "Direct graded intake, factorial training, bed rest/de-training, tracer physiology and population diet studies were considered. They answer different endpoints/scopes. Replicated oral nutrition trials remain one clinical modality, observational diet cannot fix confounding, and MPS is not an orthogonal functional causal line. No validated baseline prediction, isolated nutrient mechanism or cross-context necessity/sufficiency supports Ζ or higher for the registered above-RDA function claim." } ], "convergence_present": false, "cap_reapplied_to_convergent_set": false }, "provenance_header": { "sources_total": 57, "claims_total": 62, "claims_verified": 62, "claims_unverified": 0, "claims_contradicted": 0, "tier_a_sources": 57, "generated_by": "Codex; HSEF v5.3", "gate_passed": true }, "claims": [ { "id": "C1", "text": "208-adult one-year randomized study finds whey/collagen alone ineffective while heavy training improves quadriceps and strength No training-only arm isolates protein add-on; baseline adequate-intake healthy adults not all frail contexts", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 1 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C2", "text": "200-person pre/frail trial finds whey soy leucine or creatine do not enhance training adaptations Shared training stimulus; baseline intake and adherence matter; no denial of exercise effect", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 2 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C3", "text": "PROVIDE 380 has null between-arm handgrip/SPPB primary outcomes but positive secondary chair-rise and DXA lean mass Whey/leucine/vitamin D bundled; secondary multiplicity; lean tissue not strength; no isolated total protein claim", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 3 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C4", "text": "Retrospective 32-man mixed-supplement subgroup analysis links baseline obesity with weaker response and selected benefits Post hoc responder/subgroup analysis multi-ingredients and active collagen comparator prevent pure protein attribution", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 4 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C5", "text": "140 sarcopenic rehabilitation patients randomized to enriched whey or isocaloric formula show improved gait and function Variable 4–8-week discharge horizon multi-ingredients; modified ITT; short clinical scope not ordinary healthy adult supplementation", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 5 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Methods:paragraph1, 1:Methods:paragraph2, 1:Methods:paragraph5, 1:Methods:paragraph13, 1:Methods:paragraph33, 1:Methods:paragraph37, 2:Results:paragraph59, 2:Results:paragraph70, 2:Results:paragraph84. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C6", "text": "99-person nursing home ONS add-on trial finds no between-arm body composition or functional differences Within-group improvements are not randomized treatment effects; energy/fat/protein bundled", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 6 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C7", "text": "Open label supplement versus diet counseling has similar mass/grip outcomes and selected gait improvement Both groups target 1.2–1.5 g/kg; not RDA comparator; unblinded multi-ingredient delivery", "carries_number": false, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 7 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C8", "text": "Sarcopenia training/supplement study finds no end-intervention arm difference but selected de-training maintenance All groups instructed ≥1.2 g/kg; later subgroup/horizon; not an 0.8-versus-high protein comparison", "carries_number": false, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 8 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C9", "text": "60-person six-month enriched whey trial reports better BIA mass, grip and quality of life than isocaloric control Vitamin D/E co-interventions and BIA surrogate; small sample; no isolated protein mechanism", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 9 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C10", "text": "241-person sarcopenia factorial trial reports nutrition and exercise improvements in mass/grip Whey/fish oil/vitamin D mix; per-protocol analysis; effects need ITT and component separation", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 10 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C11", "text": "Protein/peptide trial reports SPPB, grip, mass gains in sarcopenic knee OA Ages 50–70 include outside ≥60; disease-specific proprietary mix; no separate older stratum or verified dose contrast", "carries_number": false, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 11 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C12", "text": "53 completer men collagen plus matched training show greater DXA FFM and isokinetic strength change Silica comparator not energy/protein matched; correction notice 2025 attached; no evidence every protein adds benefit", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 12 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 0:Methods:paragraph11, 0:Methods:paragraph14, 0:Methods:paragraph16, 0:Methods:paragraph17, 0:Methods:paragraph24, 1:Results:paragraph0, 1:Results:paragraph1, 1:Results:paragraph9, 1:Results:paragraph13, 1:Results:paragraph16. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C13", "text": "130 sarcopenic older adults enriched whey/EAA/vit D plus matched activity improve mass/grip/ADL versus placebo Multicomponent nutritional intervention and short 12-week horizon; cannot isolate protein quantity or vitamin component", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 13 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C14", "text": "Weight-loss factorial study finds no protein main mass effect but selected grip/gait protein-training interactions Actual intake contrast 1.13 vs 0.98 adjusted g/kg below prescribed separation; ages ≥55; secondary interaction multiplicity", "carries_number": false, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 14 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph1, 1:Methods:paragraph2, 1:Methods:paragraph5, 1:Methods:paragraph7, 2:Results:paragraph4, 2:Results:paragraph8, 2:Results:paragraph15. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C15", "text": "Combined HMB/protein/vit D/exercise trial improves BIA proxies, grip and function No factorial component control; cannot assign exercise-package benefit to protein; BIA not direct muscle", "carries_number": false, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 15 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C16", "text": "18-month factorial fortified milk study has exercise benefits but no milk add-on mass/strength/function Ages 50–79 mixed scope; exceeds registered 52-week horizon; protein/micronutrient/energy mixture", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 16 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C17", "text": "2026 exercise factorial trial assigned 0.8/1.6/2.2 targets finds no protein effect on BIA or key functional outcomes Ages 40–77; complete cases 83/108 and assigned targets not achieved intake proof; null not dose equivalence", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 17 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C18", "text": "16 older adults tracer crossover finds greater acute MPS after matched omnivorous than vegan meal Whole food matrix single meal; no chronic strength/function; not evidence plant protein cannot work", "carries_number": true, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 18 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C19", "text": "Leucine-rich EAA mixture stimulates elderly acute MPS where lower leucine mixture did not Short tracer rate not muscle accretion/function; groups small; specific composition and healthy context", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 19 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C20", "text": "Healthy older longitudinal training study finds preserved EAA MPS response and higher basal MPS with training No randomized high daily protein contrast; exercise benefit not supplementation effect; 2018 erratum attached", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC3", "SC4" ], "source_ns": [ 20 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C21", "text": "Seven-day bed rest suppresses EAA-stimulated MPS/mTOR response and reduces leg lean mass Six subjects no longer-term protein functional benefit; disuse model not universal aging resistance", "carries_number": false, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 21 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C22", "text": "120 malnourished pre-frail or frail elders randomized 0.8/1.2/1.5 g/kg for 12 weeks show 1.5-arm mass/gait improvement Primary mass not gait; modest secondary effect; 1.2-arm null; findings restricted to malnutrition/frailty", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 22 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C23", "text": "PROVIDE follow-up reports tolerability and no observed renal decline with enriched whey drink Same parent 380 RCT plus voluntary open-label extension; no evidence universal renal safety or new independent efficacy", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 23 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C24", "text": "19 pre/frail women with 1.2 g/kg and training have no added leucine MPS/strength/frailty benefit Small study; training plus adequate diet benefits do not quantify 0.8 comparison", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3", "SC4" ], "source_ns": [ 24 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C25", "text": "OPEN secondary analysis finds less caregiver time in dementia but not somatic units with combined program Same OPEN cohort as 32471657; cluster/design and resource endpoint; not isolated protein strength effect", "carries_number": false, "load_bearing_for": [ "SC3", "SC4" ], "source_ns": [ 25 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C26", "text": "47 hospitalized elders randomized whey report better grip and knee extensor recovery Hospital duration not fixed 8–52 weeks; rehab context baseline under feeding and achieved above RDA not reported abstract", "carries_number": true, "load_bearing_for": [ "SC3", "SC4" ], "source_ns": [ 26 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C27", "text": "58-person ENHANce five arm feasibility trial supplies exploratory functional signals and adherence problems Small arms 9–13 participants and low recruitment; not powered clinical component proof", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 27 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C28", "text": "218 older sarcopenic adults 12-month whey trial finds no functional, grip or mass benefit or post-trial survival difference Home-exercise advice and gastrointestinal burden; baseline context not all underfed frailty", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 28 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C29", "text": "Chinese 115-person frailty study reports between-group whey/training functional differences PubMed-indexed RCT but original abstract describes case-control; do not assume randomization; self-selection/confounding", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 29 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C30", "text": "45 older Korean adults 10-week fermented whey trial reports eSPPB between-arm improvement Nutrition profile vitamin D/calcium/magnesium changes with protein; small sample; no isolated above RDA proof", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 30 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C31", "text": "155 malnourished elders open-label BCAA-versus advice study reports energetic and selected clinical improvements Unblinded dietary/advice contrast mixed nutrient correction; peripheral ATP association not muscle mediation", "carries_number": true, "load_bearing_for": [ "SC1", "SC3", "SC4" ], "source_ns": [ 31 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C32", "text": "22 mobility limited very old adults randomized combined training/protein increase muscle size, strength, function No training-only/nutrition-only arm isolates protein; muscle-size and strength changes not correlated", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 32 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C33", "text": "OPEN cluster combined nutrition/exercise trial has null main physical function but higher weight and adherent subgroup signals Post-randomization adherence cannot define causal beneficiary; 600 kcal co-intervention; no factorial protein contrast", "carries_number": false, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 33 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C34", "text": "Postmenopause factorial trial finds RT gains without clear high protein additive effect Mean age 58.2 outside exact ≥60 average; body weight vs FFM target; within-arm gains not between-arm effect", "carries_number": false, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 34 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C35", "text": "NOURISH subset recalls show high protein ONS raises nutrient intake without food displacement 30-patient subset no direct strength/function outcome; multiple micronutrients/energy and parent trial overlap", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 35 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C36", "text": "Fish oil/whey rehabilitation pilot achieves higher protein exposure but poor recruitment and completion 20 randomized 10 complete; stopped non-feasible; no credible efficacy inference", "carries_number": false, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 36 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C37", "text": "24 older men breakfast enriched whey 6 weeks raises MPS and appendicular lean mass Vitamin D/leucine/energy versus noncaloric control; no function test; below main 8-week horizon", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC4" ], "source_ns": [ 37 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C38", "text": "Pooled original tracer data show older men require higher relative protein dose for acute MPS plateau Retrospective pooled reports not independent new trial; confidence interval wide; no chronic functional dose recommendation", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 38 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C39", "text": "14 older Chinese adults graded intake oxidation model estimates protein requirement above local recommendation IAAO surrogate requirement not strength/function; local RNI differs from 0.8 g adult reference", "carries_number": true, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 39 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C40", "text": "Obese older women hypocaloric 1.2 vs 0.8 prescribed protein study reports preserved estimated muscle mass No clear randomization; BIA/equation mass and within-arm comparison; no functional measure", "carries_number": true, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 40 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C41", "text": "Postmenopausal protein intake correlates with relative strength/dynapenia despite RDA-level intake Crosssectional mixed 50–75 age; strength/BW and protein/BW share denominator; no causality", "carries_number": false, "load_bearing_for": [ "SC3", "SC4" ], "source_ns": [ 41 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C42", "text": "60 healthy elders 24-week RT study finds no 15 g protein add-on strength, mass, function effect Moderate supplement dose and baseline adequacy; training benefit retained; not proof all supplements fail", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 42 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C43", "text": "112 older adults four-arm protein/vit D/exercise study reports combined torque/muscle quality advantage Vitamin D co-intervention; mass benefit in sarcopenic not dynapenic normal mass; endpoint-specific interaction", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 43 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C44", "text": "Fed-state insulin/amino acid clamp shows preserved muscle anabolism inactive healthy older women Infusion physiology not dietary daily high protein; no chronic functional benefit or general aging scope", "carries_number": false, "load_bearing_for": [ "SC1", "SC4" ], "source_ns": [ 44 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C45", "text": "387 older women above RDA intake group has better SPPB/PPT but not grip after BMI adjustment Crosssectional habitual intake, health confounding; no causal supplement contrast", "carries_number": true, "load_bearing_for": [ "SC3", "SC4" ], "source_ns": [ 45 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C46", "text": "10-day matched 1 g/kg source trial finds RT increases integrated MPS with no animal/plant difference Mixed age 50–70 short duration; no chronic functional or above RDA amount comparison", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3", "SC4" ], "source_ns": [ 46 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C47", "text": "Hip fracture older patients higher protein liquid 28 days improves albumin but not FIM Other nutrients differ; 4-week outside primary horizon; nutritional marker not function", "carries_number": true, "load_bearing_for": [ "SC3", "SC4" ], "source_ns": [ 47 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C48", "text": "NuAge case-control follow-up associates higher dietary protein with less subsequent weight loss Food/energy/appetite confounding; weight loss not direct muscle function and no randomized dose", "carries_number": false, "load_bearing_for": [ "SC2", "SC4" ], "source_ns": [ 48 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C49", "text": "Older adult 7-day bed rest leucine RCT preserves leg lean mass but not function Amino acid vs alanine not daily whole protein above RDA; short acute disuse outside primary horizon", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 49 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C50", "text": "Nursing home fish protein pilot shows feasibility and mixed inflammatory markers 24-person 6-week trial does not demonstrate functional benefit; retrospective registration", "carries_number": false, "load_bearing_for": [ "SC3", "SC4" ], "source_ns": [ 50 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C51", "text": "210 malnourished post-discharge elders randomized nutrition program has weight gain and subgroup functional-limit improvement ITT physical performance/grip/FFM null; energy/counseling/micronutrients bundled; exclusion-based positive", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 51 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C52", "text": "Stroke-rehab nutrition RCT has BMI/bone benefits but no strength/motor between-arm difference or renal decline Mixed age and EAA formula; no quantified above RDA protein contrast; dose/horizon context", "carries_number": false, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 52 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C53", "text": "OPTIMen 92 controlled 0.8 vs 1.3 g/kg six-month trial has null mass, strength, power and physical function Men only medically stable selected function limitations; limited precision for small benefit and no exercise stimulation", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 53 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: PMC5885156 Methods:Participants/Interventions/Exercise/Outcomes; web lines331-367, PMC5885156 Results:Compliance/LeanBodyMass/PhysicalFunction; web lines459-498. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C54", "text": "Frail 65-person 24-week protein only trial reports SPPB improvement without muscle mass increase Leg extension between-arm trend not conventional significance; actual total dose not verified original abstract; not universal benefit", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 54 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C55", "text": "Obese older adult weight loss RCT with matched RT shows enriched protein preserves appendicular lean mass but not strength/function Whey/leucine/vit D mixture; actual 1.11 vs 0.85 g/kg; lean mass benefit not functional efficacy", "carries_number": false, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 55 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C56", "text": "62 frail elders with matched 24-week training gain more DXA lean mass on protein but no additional strength/SPPB benefit Separate training trial from 65-person nutrition-only Tieland; total protein intake not quantified in original abstract; mass gain not function", "carries_number": true, "load_bearing_for": [ "SC2", "SC3", "SC4" ], "source_ns": [ 56 ], "verification": "verified", "verified_against": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-13", "note": "" }, { "id": "C57", "text": "276 community-dwelling adults aged 65 or over with habitual intake below 1.0 g/kg adjusted body weight/day: six months of dietary advice plus protein-enriched foods targeting at least 1.2 g/kg/day improved the primary 400-m walk time versus no advice (-12.4 s, 95% CI -21.8 to -2.9) and leg-extension strength (+32.6 N, 95% CI 10.6 to 54.5) Open-label; control received no advice; energy intake rose 107 kcal/day; only 37.5% reached the target and the per-protocol walk-time effect was not significant; advice-plus-timing arm -4.9 s with CI crossing zero; secondary outcomes exploratory; non-malnourished population and not an isolated protein-quantity contrast", "carries_number": true, "load_bearing_for": [ "SC3", "SC4" ], "source_ns": [ 57 ], "verification": "verified", "verified_against": "Original PMC full body text (PMC8490609) retrieved through PubMed Central on 2026-11-02 and read: Methods (design, intervention, outcomes, sample size, statistical and sensitivity analyses), Results (compliance, 400-m walk, secondary outcomes, sensitivity analyses) and Discussion limitations; tables, figures and supplements not examined. Main result also stated in the secondary report PMID 37347495 (abstract). Added after round-3 adversarial review.", "verified_on": "2026-11-02", "note": "Added after round-3 adversarial review (finding P1)." }, { "id": "CSC1", "text": "Controlled feeding and tracer studies show acute anabolic responses that vary by dose, composition, activity and health. MPS or nitrogen-turnover movement alone does not demonstrate sustained muscle accretion or functional benefit, and nutrient-sensing mediation is not isolated. The functional inference from acute synthesis evidence is held at Γ under the biomarker-only cap.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 18, 19, 20, 21, 24, 31, 37, 38, 39, 44, 46 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CSC2", "text": "Controlled older-adult nutrition studies retain positive mass/lean-tissue findings in predefined malnourished, sarcopenic or energy-deficit contexts. Other controlled trials find no mass benefit despite higher intake; DXA/BIA lean tissue is not equivalent to anatomical muscle or strength. Context-specific preservation is Ε, with source-specific body composition limits and no inference that every higher protein protocol increases muscle.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 20, 21, 22, 23, 24, 27, 28, 29, 30, 32, 33, 34, 36, 37, 40, 42, 43, 46, 48, 49, 51, 52, 53, 54, 55, 56 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CSC3", "text": "A quantified 0.8/1.2/1.5 g/kg trial in baseline malnourished pre-frail or frail elders shows a modest gait benefit at 1.5 g/kg over 12 weeks, with the intermediate arm null. A frail protein-only 24-week trial also reports SPPB benefit while mass is unchanged, though its exact total dose is not verified in the original abstract. Controlled 0.8 vs 1.3 g/kg feeding in stable function-limited men and one-year sarcopenia trials are null. An open-label six-month advice-plus-protein-enriched-foods trial in non-malnourished community-dwelling adults with habitual intake below 1.0 g/kg adjusted body weight/day also reports a primary 400-m walk benefit, with energy intake co-increased and the per-protocol effect not significant. These map context-specific human functional causality at Ε; multi-ingredient/RT package successes cannot supply a universal protein effect.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 20, 22, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 36, 41, 42, 43, 45, 46, 47, 49, 50, 51, 52, 53, 54, 55, 56, 57 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CSC4", "text": "General efficacy across adequate intake, frailty and medication-assisted weight loss without training is not established. Predefined nutrition, training, formulation and energy balance modify outcomes; some frail cohorts are null. The GLP-1 lean-mass protection claim needs direct protein/training results rather than DXA loss narratives. Partial physiological plausibility remains Γ, not a validated generalization rule or a blanket claim that every older person needs the same high dose.", "carries_number": false, "load_bearing_for": [ "SC4" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-13", "note": "" }, { "id": "CH", "text": "Higher protein intake can improve selected muscle outcomes in some older adults - most clearly in nutritionally vulnerable groups, with one open-label trial also reporting a walking benefit in community-dwelling adults whose habitual intake was near the allowance; other controlled trials at similar intake find no benefit, and lean-mass changes do not establish stronger or more functional muscle.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 22, 53, 1, 54, 55, 3, 57 ], "verification": "verified", "verified_against": "Bounded synthesis of examined sources; score is adjudication.", "verified_on": "2026-10-13", "note": "" } ], "citation_ledger": [ { "n": 1, "citation": "Mertz KH, Reitelseder S, Bechshoeft R et al. 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Effects of adequate dietary protein with whey protein, leucine, and vitamin D supplementation on sarcopenia in older adults: An open-label, parallel-group study. Clinical nutrition (Edinburgh, Scotland). 2021.", "tier": "A", "kind": "rct", "pmid": "32928579", "doi": "10.1016/j.clnu.2020.08.017", "url": "https://pubmed.ncbi.nlm.nih.gov/32928579/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID32928579", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C7", "CSC2", "CSC3", "CSC4" ] }, { "n": 8, "citation": "Mori H, Tokuda Y. De-Training Effects Following Leucine-Enriched Whey Protein Supplementation and Resistance Training in Older Adults with Sarcopenia: A Randomized Controlled Trial with 24 Weeks of Follow-Up. The journal of nutrition, health & aging. 2022.", "tier": "A", "kind": "rct", "pmid": "36437767", "doi": "10.1007/s12603-022-1853-1", "url": "https://pubmed.ncbi.nlm.nih.gov/36437767/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID36437767", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C8", "CSC2", "CSC3", "CSC4" ] }, { "n": 9, "citation": "Bo Y, Liu C, Ji Z et al. A high whey protein, vitamin D and E supplement preserves muscle mass, strength, and quality of life in sarcopenic older adults: A double-blind randomized controlled trial. Clinical nutrition (Edinburgh, Scotland). 2019.", "tier": "A", "kind": "rct", "pmid": "29395372", "doi": "10.1016/j.clnu.2017.12.020", "url": "https://pubmed.ncbi.nlm.nih.gov/29395372/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID29395372", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C9", "CSC2", "CSC3", "CSC4" ] }, { "n": 10, "citation": "Li Z, Cui M, Yu K et al. Effects of nutrition supplementation and physical exercise on muscle mass, muscle strength and fat mass among sarcopenic elderly: a randomized controlled trial. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2021.", "tier": "A", "kind": "rct", "pmid": "33216623", "doi": "10.1139/apnm-2020-0643", "url": "https://pubmed.ncbi.nlm.nih.gov/33216623/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID33216623", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C10", "CSC2", "CSC3", "CSC4" ] }, { "n": 11, "citation": "Wu Q, Xu Z, Huang W et al. Effect of high plant protein/peptide nutrition supplementation on knee osteoarthritis in older adults with sarcopenia: A randomized, double-blind, placebo-controlled trial. Clinical nutrition (Edinburgh, Scotland). 2024.", "tier": "A", "kind": "rct", "pmid": "39142111", "doi": "10.1016/j.clnu.2024.07.037", "url": "https://pubmed.ncbi.nlm.nih.gov/39142111/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID39142111", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C11", "CSC2", "CSC3", "CSC4" ] }, { "n": 12, "citation": "Zdzieblik D, Oesser S, Baumstark MW et al. Collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men: a randomised controlled trial. The British journal of nutrition. 2015.", "tier": "A", "kind": "rct", "pmid": "26353786", "doi": "10.1017/S0007114515002810", "url": "https://pubmed.ncbi.nlm.nih.gov/26353786/", "status_flags": [ "ErratumIn: PMID40859798" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID26353786", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 0:Methods:paragraph11, 0:Methods:paragraph14, 0:Methods:paragraph16, 0:Methods:paragraph17, 0:Methods:paragraph24, 1:Results:paragraph0, 1:Results:paragraph1, 1:Results:paragraph9, 1:Results:paragraph13, 1:Results:paragraph16. No complete-paper or supplement audit claimed.", "carries_claims": [ "C12", "CSC2", "CSC3", "CSC4" ] }, { "n": 13, "citation": "Rondanelli M, Klersy C, Terracol G et al. Whey protein, amino acids, and vitamin D supplementation with physical activity increases fat-free mass and strength, functionality, and quality of life and decreases inflammation in sarcopenic elderly. The American journal of clinical nutrition. 2016.", "tier": "A", "kind": "rct", "pmid": "26864356", "doi": "10.3945/ajcn.115.113357", "url": "https://pubmed.ncbi.nlm.nih.gov/26864356/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID26864356", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C13", "CSC2", "CSC3", "CSC4" ] }, { "n": 14, "citation": "Verreijen AM, Engberink MF, Memelink RG et al. Effect of a high protein diet and/or resistance exercise on the preservation of fat free mass during weight loss in overweight and obese older adults: a randomized controlled trial. Nutrition journal. 2017.", "tier": "A", "kind": "rct", "pmid": "28166780", "doi": "10.1186/s12937-017-0229-6", "url": "https://pubmed.ncbi.nlm.nih.gov/28166780/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID28166780", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph1, 1:Methods:paragraph2, 1:Methods:paragraph5, 1:Methods:paragraph7, 2:Results:paragraph4, 2:Results:paragraph8, 2:Results:paragraph15. No complete-paper or supplement audit claimed.", "carries_claims": [ "C14", "CSC2", "CSC3", "CSC4" ] }, { "n": 15, "citation": "Sun J, He M, Chen M et al. Effects of combined nutritional supplementation and exercise on proxy measures of muscle mass, strength, and function in older adults with sarcopenia: a 12-week multicentre RCT. Nutrition journal. 2025.", "tier": "A", "kind": "rct", "pmid": "41350709", "doi": "10.1186/s12937-025-01244-z", "url": "https://pubmed.ncbi.nlm.nih.gov/41350709/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID41350709", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C15", "CSC2", "CSC3", "CSC4" ] }, { "n": 16, "citation": "Kukuljan S, Nowson CA, Sanders K et al. Effects of resistance exercise and fortified milk on skeletal muscle mass, muscle size, and functional performance in middle-aged and older men: an 18-mo randomized controlled trial. 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The journal of nutrition, health & aging. 2014.", "tier": "A", "kind": "primary", "pmid": "24522467", "doi": "10.1007/s12603-013-0391-2", "url": "https://pubmed.ncbi.nlm.nih.gov/24522467/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID24522467", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C45", "CSC3", "CSC4" ] }, { "n": 46, "citation": "Korzepa M, Quinlan JI, Marshall RN et al. Resistance training increases myofibrillar protein synthesis in middle-to-older aged adults consuming a typical diet with no influence of protein source: a randomized controlled trial. The American journal of clinical nutrition. 2025.", "tier": "A", "kind": "rct", "pmid": "40288581", "doi": "10.1016/j.ajcnut.2025.04.019", "url": "https://pubmed.ncbi.nlm.nih.gov/40288581/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID40288581", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C46", "CSC1", "CSC2", "CSC3", "CSC4" ] }, { "n": 47, "citation": "Neumann M, Friedmann J, Roy MA et al. Provision of high-protein supplement for patients recovering from hip fracture. Nutrition (Burbank, Los Angeles County, Calif.). 2004.", "tier": "A", "kind": "rct", "pmid": "15105027", "doi": "10.1016/j.nut.2004.01.004", "url": "https://pubmed.ncbi.nlm.nih.gov/15105027/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID15105027", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C47", "CSC3", "CSC4" ] }, { "n": 48, "citation": "Gray-Donald K, St-Arnaud-McKenzie D, Gaudreau P et al. Protein intake protects against weight loss in healthy community-dwelling older adults. The Journal of nutrition. 2014.", "tier": "A", "kind": "primary", "pmid": "24357473", "doi": "10.3945/jn.113.184705", "url": "https://pubmed.ncbi.nlm.nih.gov/24357473/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID24357473", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C48", "CSC2", "CSC4" ] }, { "n": 49, "citation": "Arentson-Lantz EJ, Fiebig KN, Anderson-Catania KJ et al. Countering disuse atrophy in older adults with low-volume leucine supplementation. Journal of applied physiology (Bethesda, Md. : 1985). 2020.", "tier": "A", "kind": "rct", "pmid": "32191600", "doi": "10.1152/japplphysiol.00847.2019", "url": "https://pubmed.ncbi.nlm.nih.gov/32191600/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID32191600", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C49", "CSC2", "CSC3", "CSC4" ] }, { "n": 50, "citation": "Drotningsvik A, Oterhals Å, Flesland O et al. Fish protein supplementation in older nursing home residents: a randomised, double-blind, pilot study. Pilot and feasibility studies. 2019.", "tier": "A", "kind": "primary", "pmid": "30858985", "doi": "10.1186/s40814-019-0421-x", "url": "https://pubmed.ncbi.nlm.nih.gov/30858985/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID30858985", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C50", "CSC3", "CSC4" ] }, { "n": 51, "citation": "Neelemaat F, Bosmans JE, Thijs A et al. Post-discharge nutritional support in malnourished elderly individuals improves functional limitations. Journal of the American Medical Directors Association. 2011.", "tier": "A", "kind": "rct", "pmid": "21527171", "doi": "10.1016/j.jamda.2010.12.005", "url": "https://pubmed.ncbi.nlm.nih.gov/21527171/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID21527171", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C51", "CSC2", "CSC3", "CSC4" ] }, { "n": 52, "citation": "Nakagawa N, Koyama S, Maruyama K et al. Effects of Nutritional Support with a Leucine-Enriched Essential Amino Acid Supplement on Body Composition, Muscle Strength, and Physical Function in Stroke Patients Undergoing Rehabilitation. Nutrients. 2024.", "tier": "A", "kind": "rct", "pmid": "39770886", "doi": "10.3390/nu16244264", "url": "https://pubmed.ncbi.nlm.nih.gov/39770886/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID39770886", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C52", "CSC2", "CSC3", "CSC4" ] }, { "n": 53, "citation": "Bhasin S, Apovian CM, Travison TG et al. Effect of Protein Intake on Lean Body Mass in Functionally Limited Older Men: A Randomized Clinical Trial. JAMA internal medicine. 2018.", "tier": "A", "kind": "rct", "pmid": "29532075", "doi": "10.1001/jamainternmed.2018.0008", "url": "https://pubmed.ncbi.nlm.nih.gov/29532075/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID29532075", "access_depth": "full_text_partial", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. Selected body sections: PMC5885156 Methods:Participants/Interventions/Exercise/Outcomes; web lines331-367, PMC5885156 Results:Compliance/LeanBodyMass/PhysicalFunction; web lines459-498. No complete-paper or supplement audit claimed.", "carries_claims": [ "C53", "CSC2", "CSC3", "CSC4", "CH" ] }, { "n": 54, "citation": "Tieland M, van de Rest O, Dirks ML et al. Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trial. Journal of the American Medical Directors Association. 2012.", "tier": "A", "kind": "rct", "pmid": "22889730", "doi": "10.1016/j.jamda.2012.07.005", "url": "https://pubmed.ncbi.nlm.nih.gov/22889730/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Tieland_nutritiononly_NCT01109628", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C54", "CSC2", "CSC3", "CSC4", "CH" ] }, { "n": 55, "citation": "Verreijen AM, Verlaan S, Engberink MF et al. A high whey protein-, leucine-, and vitamin D-enriched supplement preserves muscle mass during intentional weight loss in obese older adults: a double-blind randomized controlled trial. The American journal of clinical nutrition. 2015.", "tier": "A", "kind": "rct", "pmid": "25646324", "doi": "10.3945/ajcn.114.090290", "url": "https://pubmed.ncbi.nlm.nih.gov/25646324/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "PMID25646324", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C55", "CSC2", "CSC3", "CSC4", "CH" ] }, { "n": 56, "citation": "Tieland M, Dirks ML, van der Zwaluw N et al. Protein supplementation increases muscle mass gain during prolonged resistance-type exercise training in frail elderly people: a randomized, double-blind, placebo-controlled trial. Journal of the American Medical Directors Association. 2012.", "tier": "A", "kind": "rct", "pmid": "22770932", "doi": "10.1016/j.jamda.2012.05.020", "url": "https://pubmed.ncbi.nlm.nih.gov/22770932/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-13", "status_checked_on": "2026-10-13", "study_id": "Tieland_training_NCT01110369", "access_depth": "abstract_metadata", "access_note": "Bounded original primary abstract Results/Findings/conclusion passages and linked-status metadata examined; no complete-abstract audit asserted. No complete-paper or supplement audit claimed.", "carries_claims": [ "C56", "CSC2", "CSC3", "CSC4" ] }, { "n": 57, "citation": "Reinders I, Visser M, Jyväkorpi SK et al. The cost effectiveness of personalized dietary advice to increase protein intake in older adults with lower habitual protein intake: a randomized controlled trial. European journal of nutrition. 2021.", "tier": "A", "kind": "rct", "pmid": "34609621", "doi": "10.1007/s00394-021-02675-0", "url": "https://pubmed.ncbi.nlm.nih.gov/34609621/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-11-02", "status_checked_on": "2026-11-02", "study_id": "PMID34609621", "access_depth": "full_text_partial", "access_note": "Original PMC full body text (PMC8490609) retrieved through PubMed Central on 2026-11-02 and read: Methods (design, intervention, outcomes, sample size, statistical and sensitivity analyses), Results (compliance, 400-m walk, secondary outcomes, sensitivity analyses) and Discussion limitations; tables, figures and supplements not examined. Main result also stated in the secondary report PMID 37347495 (abstract). Added after round-3 adversarial review.", "carries_claims": [ "C57", "CSC3", "CSC4", "CH" ] } ], "independence_basis": { "required": false, "lines": [ { "label": "Randomized dietary protein dose", "sources": [ 22, 53 ], "excludes_error": "Direct dose and energy controls reduce habitual diet selection; outcomes differ by baseline context, preventing universal causality." }, { "label": "Mechanical loading contrasts", "sources": [ 1, 42, 2 ], "excludes_error": "Training-versus-nutrition designs test the assumption that package benefit comes from protein; they do not form a second positive dietary protein line." }, { "label": "Tracer/disuse and endpoint dissociation", "sources": [ 19, 21, 49, 55 ], "excludes_error": "Biopsy/kinetic and bed rest tests detect anabolism and mass/function separation by different readouts, but do not prove the primary chronic above-RDA functional claim." } ], "shared_failure_mode_checked": true, "note": "Complementary checks exclude different errors, but cannot be combined as independent positive lines for the same complete claim. Tracer physiology, chronic function and cross-sectional diet are not interchangeable evidence classes. PROVIDE follow-up is one parent study; OPEN caregiver-time analysis is one OPEN cohort; retrospective/subgroup reports preserve parent grouping." }, "gamma_hard_rules_considered": [ { "subclaim_id": "SC1", "rule_quoted": "ROS change measurements alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC1", "rule_quoted": "NAD level change measurements alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC1", "rule_quoted": "Mitochondrial metrics alone", "trigger_status": "Not triggered literally for this assembled scoped case. 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Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC3", "rule_quoted": "Single-species or single-strain evidence", "trigger_status": "not an animal-to-human generalization inference; registered human clinical intervention scope is directly tested" }, { "subclaim_id": "SC3", "rule_quoted": "Biomarker-only improvement without organismal benefit", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "ROS change measurements alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "NAD level change measurements alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "Mitochondrial metrics alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "Senescence marker changes alone", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "Single-species or single-strain evidence", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." }, { "subclaim_id": "SC4", "rule_quoted": "Biomarker-only improvement without organismal benefit", "trigger_status": "Not triggered literally for this assembled scoped case. Any adapted clinical, proxy or system-inference restriction is stated separately in the subclaim rationale." } ], "consensus_validation": { "completed": true, "status": "completed_original_source_reconciliation", "provider_mode": "Consensus Pro signed-in browser; observed output and citation link mappings", "queries": [ "https://consensus.app/search/dietary-protein-effects-older-adults/DudKItpNSg-OZEBY4542Zw/" ], "query_record_note": "Exact visible question/response retained privately in raw browser receipt.", "primary_comparison_count": 10, "primary_comparisons": [ { "pmid": "33564844", "doi": "10.1093/ajcn/nqaa372", "source_type": "primary study report", "study_group": "PMID33564844", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus states that supplied CALM evidence concerns cognitive-training abstracts and gives no usable protein results.", "result_comparison": "The examined original 2021 nutrition trial has 208 older adults randomized to carbohydrate, collagen, whey, light training plus whey, or heavy training plus whey for one year. Protein-only arms are null; loading contrasts are positive. This is a retrieval identity error, not missing literature, and no training-only arm proves whey synergy.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/33564844/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\protein-muscle-aging\\examinations\\original-0-6-12000.json" ], "body_receipts": [] }, { "pmid": "22889730", "doi": "10.1016/j.jamda.2012.07.005", "source_type": "primary study report", "study_group": "Tieland_nutritiononly_NCT01109628", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus retrieves Tieland training but omits the requested nutrition-only trial.", "result_comparison": "The separate original 65-person nutrition-only trial reports a positive SPPB interaction without lean-mass gain; leg-extension strength is only a trend. This positive functional result prevents an unqualified no-benefit summary. Exact achieved total protein remains unverified at our abstract access depth.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/22889730/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\protein-muscle-aging\\examinations\\original-52-55-12000.json" ], "body_receipts": [] }, { "pmid": "22770932", "doi": "10.1016/j.jamda.2012.05.020", "source_type": "primary study report", "study_group": "Tieland_training_NCT01110369", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus correctly describes 62 frail adults with matched training and protein-associated lean-mass gain but no added strength or SPPB effect.", "result_comparison": "Original abstract agrees. It is NCT01110369, separate from the 65-person nutrition-only NCT01109628 study. Their endpoint difference does not represent duplicate reporting or contradictory measurements in the same cohort.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/22770932/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\protein-muscle-aging\\examinations\\original-55-56-12000.json" ], "body_receipts": [] }, { "pmid": "26170041", "doi": "10.1016/j.jamda.2015.05.021", "source_type": "primary study report", "study_group": "PROVIDE_NTR2323", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus says PROVIDE primary grip and SPPB results are null, with secondary chair-rise and appendicular mass benefits.", "result_comparison": "Original abstract agrees with this endpoint hierarchy. Vitamin D, leucine, whey and other nutrients are bundled; the benefit cannot be assigned to protein quantity alone or described as a positive primary functional trial.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/26170041/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\protein-muscle-aging\\examinations\\original-0-6-12000.json" ], "body_receipts": [] }, { "pmid": "29532075", "doi": "10.1001/jamainternmed.2018.0008", "source_type": "primary study report", "study_group": "PMID29532075", "access_depth": "full_text_partial", "consensus_aspect": "Consensus identifies the controlled 0.8 versus 1.3 g/kg/day functional null and factorial testosterone design.", "result_comparison": "Original selected PMC Methods/Results confirms controlled energy, intake checks and separately analyzed outcomes. This strong null in its baseline-defined group is retained without generalizing to every malnourished or frail older adult.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/29532075/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\protein-muscle-aging\\examinations\\original-52-55-12000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\protein-muscle-aging\\body-presentation-receipts\\29532075-selected-public-html.json" ] }, { "pmid": "25646324", "doi": "10.3945/ajcn.114.090290", "source_type": "primary study report", "study_group": "PMID25646324", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus lacks the original 2015 weight-loss trial and passes along review-level suggestions of mass and function benefit.", "result_comparison": "Original abstract verifies 80 participants, matched resistance training, actual intake 1.11 versus 0.85 g/kg/day, and preserved appendicular lean mass. Strength and physical function improve over time without between-arm differences; review-level language cannot replace that functional null.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/25646324/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\protein-muscle-aging\\examinations\\original-52-55-12000.json" ], "body_receipts": [] }, { "pmid": "30475969", "doi": "10.1093/ajcn/nqy214", "source_type": "primary study report", "study_group": "PMID30475969", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus headline says higher protein usually does not improve strength or overall function and does not recover Park2018.", "result_comparison": "Original 120-person randomized trial in malnourished prefrail/frail elders directly compares 0.8, 1.2 and 1.5 g/kg/day: highest-dose mass and secondary gait improvement are positive, intermediate-dose outcomes null. The scoped clinical positive is retained while rejecting a universal dose rule.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/30475969/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\protein-muscle-aging\\examinations\\original-19-25-12000.json" ], "body_receipts": [] }, { "pmid": "28166780", "doi": "10.1186/s12937-017-0229-6", "source_type": "primary study report", "study_group": "PMID28166780", "access_depth": "full_text_partial", "consensus_aspect": "Consensus identifies achieved intake reporting as a gap but does not recover this original factorial detail.", "result_comparison": "Original Methods/Results shows prescribed targets differ from achieved intake, no fat-free-mass protein main or interaction effect, and selected grip/gait interactions. Secondary interactions and positive within-arm changes are not interchangeable with a general protein effect.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/28166780/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\protein-muscle-aging\\examinations\\original-12-19-12000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\protein-muscle-aging\\body-presentation-receipts\\28166780-s1-p0-1-2-5-7.json", "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\protein-muscle-aging\\body-presentation-receipts\\28166780-s2-p4-8-15.json" ] }, { "pmid": "32162241", "doi": "10.1007/s40520-020-01519-x", "source_type": "primary study report", "study_group": "PROVIDE_NTR2323", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus repeats PROVIDE-related supplement and tolerability evidence alongside clinical outcomes.", "result_comparison": "Original abstract identifies the same 380-person RCT plus voluntary open-label extension. It informs product-specific tolerability over six months, not a new independent causal efficacy line or universal renal safety.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/32162241/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\protein-muscle-aging\\examinations\\original-19-25-12000.json" ], "body_receipts": [] }, { "pmid": "32471657", "doi": "10.1016/j.jamda.2020.03.030", "source_type": "primary study report", "study_group": "OPEN_NCT02702037", "access_depth": "abstract_metadata", "consensus_aspect": "Consensus notes reporting and context gaps but does not detail postrandomization adherence selection.", "result_comparison": "Original OPEN abstract has a null main function result, with body-weight and high-adherence subgroup signals. Adherence after allocation cannot define a preregistered beneficiary group; caregiver-time reanalysis is the same trial.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/32471657/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\protein-muscle-aging\\examinations\\original-31-37-12000.json" ], "body_receipts": [] } ], "grade_changed": false, "grade_change_note": "Source-based adjudication; no independent blinded regrade claimed.", "raw_receipts": [ { "path": "deliverables\\hsef_v53_traffic_first_five_2026-10-12\\protein-muscle-aging\\consensus-browser-2026-10-12.json", "sha256": "de80a37b1755de99f0c3898a554c32d006f272bd7bdc4494c31562748e659bda" } ], "independent_blinded_audit": false, "cutoff": "2026-10-12", "completed_utc": "2026-10-13T06:25:03.588422+00:00", "conclusion": "Endpoint hierarchy, experimental scope and original-source limits determine the evidence cards; provider wording does not override them." } }