{"name":"Amino acid evidence chart","url":"https://impower.life/evidence","publisher":"IMPOWERLIFE™","authors":[{"name":"Kevin Ramirez","role":"Co-founder and supplement formulator","url":"https://impower.life/about"},{"name":"Marianne Boctor","role":"Co-founder and chemical engineer","url":"https://impower.life/about"}],"license":{"name":"Creative Commons Attribution 4.0 International (CC BY 4.0)","url":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},"rubric_version":"0.2-draft","first_published":"2026-09-15","last_modified":"2026-10-22","citations_verified_on":"2026-10-22","independent_review":"pending","methods":[{"title":"What is included","text":"Twenty-five compounds people ask about, each paired with the outcomes it is most often sold for: 68 compound-and-outcome entries resting on 110 citations. Compounds IMPOWERLIFE™ does not sell are included. Null results, mixed results and harm signals about compounds it does sell are included."},{"title":"How citations were found and checked","text":"Every citation was located through PubMed E-utilities and its title, journal, year and PMID recorded from the PubMed record. Effect statements come from the PubMed abstract unless the entry's caveat says otherwise. All PMIDs were re-resolved on 2026-10-22; the GLP-1 entry was also checked against ClinicalTrials.gov that day."},{"title":"How grades are assigned","text":"Five levels, rubric version 0.2-draft, assigned conservatively for the compound, outcome and population studied. The lowest grade covers two different situations, \"not studied in humans\" and \"studied with no effect or conflicting results\"; the direction field on each entry says which. A grade never describes POWER9®: it describes the ingredient at the dose the trial used."},{"title":"Exclusions and study-type mapping","text":"A companion taurine heart-failure paper (Ahmadian 2017, PMID 28118062) is flagged retracted in PubMed and is excluded. Narrative reviews, pooled secondary analyses and preclinical studies are recorded under the nearest schema study type and flagged in the entry's caveat so the mapping is visible."},{"title":"Bubble size","text":"Bubble size = relative interest, not effectiveness: 70% English Wikipedia pageviews (Aug 2025-Aug 2026, user agent only) + 30% PubMed title/abstract mention count, log-scaled 10-100."},{"title":"Review status","text":"Independent review: pending. The grades were assigned by the authors and have not yet been signed by a licensed professional; the reviewer's name and date will appear here when they are."}],"grade_rubric":{"1":"No evidence or conflicting","2":"Slight","3":"Promising","4":"Good","5":"Strong"},"entry_count":68,"entries":[{"id":"leucine-mps-older","url":"https://impower.life/evidence#leucine-mps-older","compound":"Leucine","compound_full":"Leucine","compound_group":"Essential","outcome":"Muscle protein synthesis and lean mass in older adults","situations":"Adults 65+","grade":4,"grade_label":"Good","direction":"Mixed results","population":"Older adults (healthy and sarcopenic)","dose_studied":"Varied across trials; not pooled in abstract","summary":"Meta-analysis of 9 RCTs shows leucine raises muscle protein fractional synthetic rate (SMD 1.08) but no significant gain in lean body mass or leg lean mass; a second meta-analysis (16 studies, n=999) found +0.99 kg lean mass, mainly in sarcopenic subjects, with no strength benefit. Consistent on MPS, inconsistent on body composition.","caveat":"","citation_title":"The effectiveness of leucine on muscle protein synthesis, lean body mass and leg lean mass accretion in older people: a systematic review and meta-analysis.","journal":"British Journal of Nutrition","year":2015,"pmid":"25234223","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/25234223/","study_type":"meta-analysis","sample":"9 RCTs","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"leucine-rt-young","url":"https://impower.life/evidence#leucine-rt-young","compound":"Leucine","compound_full":"Leucine","compound_group":"Essential","outcome":"Muscle mass and strength with resistance training (young adults)","situations":"Building muscle","grade":1,"grade_label":"No evidence or conflicting","direction":"No effect or untested","population":"Healthy untrained young adults","dose_studied":"3 g/day (post-training); 6 g/day in recovery trial","summary":"Free leucine (3 g/day post-training) added to 8 weeks of resistance training produced no additional muscle CSA or strength gain in young adults eating adequate protein; a crossover trial found 6 g/day did not improve recovery either. No positive trials located.","caveat":"","citation_title":"Free leucine supplementation during an 8-week resistance training program does not increase muscle mass and strength in untrained young adult subjects.","journal":"Amino Acids","year":2017,"pmid":"28444456","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/28444456/","study_type":"RCT","sample":"20","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"bcaa-mps-acute","url":"https://impower.life/evidence#bcaa-mps-acute","compound":"BCAAs","compound_full":"BCAAs (leucine, isoleucine, valine)","compound_group":"Essential","outcome":"Acute muscle protein synthesis after resistance exercise","situations":"Building muscle","grade":2,"grade_label":"Slight","direction":"Mixed results","population":"Resistance-trained young men","dose_studied":"5.6 g BCAA post-exercise","summary":"One tracer study (n=10) shows 5.6 g BCAA alone raised myofibrillar MPS 22% after exercise, but the same field's leading review concludes BCAAs alone cannot sustain an anabolic response because the other EAAs must come from muscle breakdown; direct comparison shows EAA > BCAA > leucine for mTORC1 signalling. Mechanistic, small-n, and sub-maximal.","caveat":"Wolfe 2017 is a narrative review recorded under the nearest schema study type (systematic review).","citation_title":"Branched-Chain Amino Acid Ingestion Stimulates Muscle Myofibrillar Protein Synthesis following Resistance Exercise in Humans.","journal":"Frontiers in Physiology","year":2017,"pmid":"28638350","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/28638350/","study_type":"RCT","sample":"10 (crossover)","supporting_citations":2,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"bcaa-hypertrophy","url":"https://impower.life/evidence#bcaa-hypertrophy","compound":"BCAAs","compound_full":"BCAAs (leucine, isoleucine, valine)","compound_group":"Essential","outcome":"Muscle mass and strength gains with resistance training","situations":"Building muscle","grade":1,"grade_label":"No evidence or conflicting","direction":"No effect or untested","population":"Postmenopausal women; adults 50+","dose_studied":"9 g/day","summary":"Adding 9 g/day BCAA to 8 weeks of resistance training in postmenopausal women did not augment muscle mass or strength versus placebo; a BCAA-based multi-ingredient product plus exercise in adults 50+ showed no between-group difference in appendicular muscle mass; the Wolfe review argues BCAAs alone cannot build muscle. Tested and failed for hypertrophy.","caveat":"Peng 2022's title says 'improved muscle mass' but the abstract reports no significant between-group difference in appendicular muscle mass; only an MRI sub-group thigh difference.","citation_title":"Effects of branched-chain amino acid supplementation and resistance training in postmenopausal women.","journal":"Experimental Gerontology","year":2021,"pmid":"33279662","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/33279662/","study_type":"RCT","sample":"30","supporting_citations":2,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"bcaa-doms","url":"https://impower.life/evidence#bcaa-doms","compound":"BCAAs","compound_full":"BCAAs (leucine, isoleucine, valine)","compound_group":"Essential","outcome":"Delayed-onset muscle soreness / exercise-induced muscle damage","situations":"Building muscle","grade":3,"grade_label":"Promising","direction":"Benefit shown","population":"Healthy adults, mostly recreationally active","dose_studied":">200 mg/kg/day for >10 days, taken before damaging exercise","summary":"Meta-analysis reports a large reduction in DOMS (ES 0.73) but pools only 8 studies with 61 total participants; a systematic review of 11 studies finds benefit only when damage is low-to-moderate and dosing is high (>200 mg/kg/day for >10 days). Positive but small evidence base with high heterogeneity.","caveat":"","citation_title":"Effect of branched-Chain Amino Acid Supplementation on Muscle Soreness following Exercise: A Meta-Analysis.","journal":"International Journal for Vitamin and Nutrition Research","year":2019,"pmid":"30938579","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/30938579/","study_type":"meta-analysis","sample":"8 studies, 61 participants","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"eaa-mps","url":"https://impower.life/evidence#eaa-mps","compound":"EAA blend","compound_full":"Essential amino acid blend (EAA)","compound_group":"Essential","outcome":"Muscle protein synthesis / anabolic response to feeding","situations":"Building muscle","grade":4,"grade_label":"Good","direction":"Benefit shown","population":"Healthy young and older adults","dose_studied":"3.2-18 g EAA per dose","summary":"Consistent stable-isotope studies: EAAs alone reproduce the full anabolic effect of a balanced amino acid mix (non-essentials add nothing); an EAA + whey composition was 3-6x more anabolic per gram than a whey-based recovery drink; pooled analysis shows peak plasma EAA concentration is the strongest predictor of MPS. Mechanistically robust, but long-term hypertrophy RCTs of free EAA vs placebo are scarce.","caveat":"Church 2020 is a pooled secondary analysis, recorded as a cohort study for schema compatibility.","citation_title":"Essential amino acids are primarily responsible for the amino acid stimulation of muscle protein anabolism in healthy elderly adults.","journal":"American Journal of Clinical Nutrition","year":2003,"pmid":"12885705","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/12885705/","study_type":"RCT","sample":"14","supporting_citations":3,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"protein-hypertrophy","url":"https://impower.life/evidence#protein-hypertrophy","compound":"Protein (comparator)","compound_full":"Protein supplement (whey/casein/soy; comparator)","compound_group":"Derivative","outcome":"Muscle mass and strength gains with resistance training","situations":"Building muscle","grade":5,"grade_label":"Strong","direction":"Benefit shown","population":"Healthy adults performing resistance training","dose_studied":"Total protein up to ~1.6 g/kg/day","summary":"Meta-analysis of 49 RCTs (n=1863) shows protein supplementation significantly increases 1RM strength (+2.49 kg), fat-free mass (+0.30 kg) and fibre CSA during resistance training; benefit plateaus above ~1.6 g/kg/day and shrinks with age. Large, consistent evidence base.","caveat":"","citation_title":"A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults.","journal":"British Journal of Sports Medicine","year":2018,"pmid":"28698222","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/28698222/","study_type":"meta-analysis","sample":"49 studies, 1863 participants","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"creatine-strength","url":"https://impower.life/evidence#creatine-strength","compound":"Creatine","compound_full":"Creatine","compound_group":"Derivative","outcome":"Strength performance (lower and upper limb)","situations":"Building muscle","grade":5,"grade_label":"Strong","direction":"Benefit shown","population":"Healthy adults of varied age and training status","dose_studied":"Varied; meta-regression found effect independent of dose and loading","summary":"Two large meta-analyses of placebo-controlled RCTs (60 studies lower limb, 53 studies upper limb; >1,100 participants each) show consistent strength gains for efforts under 3 minutes, independent of age, sex, training status or dose.","caveat":"","citation_title":"Creatine Supplementation and Lower Limb Strength Performance: A Systematic Review and Meta-Analyses.","journal":"Sports Medicine","year":2015,"pmid":"25946994","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/25946994/","study_type":"meta-analysis","sample":"60 studies, 1297 participants","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"creatine-lean-older","url":"https://impower.life/evidence#creatine-lean-older","compound":"Creatine","compound_full":"Creatine","compound_group":"Derivative","outcome":"Lean tissue mass and strength with resistance training in older adults","situations":"Adults 65+","grade":5,"grade_label":"Strong","direction":"Benefit shown","population":"Older adults (57-70 y) performing resistance training","dose_studied":"<=5 g/day or >5 g/day, with or without loading; 7-52 weeks","summary":"Meta-analysis of 22 RCTs (n=721, mean age 57-70) shows creatine plus resistance training adds +1.37 kg lean tissue and improves chest- and leg-press strength versus placebo; an updated 2021 meta-analysis confirms the lean-mass effect across dosing strategies.","caveat":"","citation_title":"Effect of creatine supplementation during resistance training on lean tissue mass and muscular strength in older adults: a meta-analysis.","journal":"Open Access Journal of Sports Medicine","year":2017,"pmid":"29138605","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/29138605/","study_type":"meta-analysis","sample":"22 studies, 721 participants","supporting_citations":2,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"creatine-memory","url":"https://impower.life/evidence#creatine-memory","compound":"Creatine","compound_full":"Creatine","compound_group":"Derivative","outcome":"Memory / cognition","situations":"Mood and sleep","grade":3,"grade_label":"Promising","direction":"Mixed results","population":"Healthy adults; benefit confined to 66-76 y subgroup","dose_studied":"~2.2-20 g/day for 5 days to 24 weeks","summary":"Meta-analysis of 8 RCTs finds a small overall memory improvement (SMD 0.29, I2 66%) driven by older adults (SMD 0.88); no effect in younger participants (SMD 0.03). Positive but heterogeneous and age-dependent.","caveat":"","citation_title":"Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials.","journal":"Nutrition Reviews","year":2023,"pmid":"35984306","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/35984306/","study_type":"meta-analysis","sample":"8 RCTs in meta-analysis","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"hmb-athletes","url":"https://impower.life/evidence#hmb-athletes","compound":"HMB","compound_full":"HMB (beta-hydroxy-beta-methylbutyrate)","compound_group":"Derivative","outcome":"Strength and body composition in trained athletes / young adults","situations":"Building muscle","grade":1,"grade_label":"No evidence or conflicting","direction":"No effect or untested","population":"Trained/competitive athletes; young adults 18-45","dose_studied":"Typically 3 g/day (subgroups by dose showed no difference)","summary":"Two meta-analyses agree there is no effect: in trained athletes all effect sizes were trivial and non-significant (6 RCTs, n=193); in 18-45 year-olds HMB did not improve fat-free mass, fat mass or strength during resistance training (11 studies, n=302). Tested and failed in this population.","caveat":"","citation_title":"Effects of beta-hydroxy-beta-methylbutyrate supplementation on strength and body composition in trained and competitive athletes: A meta-analysis of randomized controlled trials.","journal":"Journal of Science and Medicine in Sport","year":2018,"pmid":"29249685","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/29249685/","study_type":"meta-analysis","sample":"6 studies, 193 participants","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"hmb-older","url":"https://impower.life/evidence#hmb-older","compound":"HMB","compound_full":"HMB (beta-hydroxy-beta-methylbutyrate)","compound_group":"Derivative","outcome":"Muscle mass preservation in older adults / bed rest","situations":"Adults 65+","grade":4,"grade_label":"Good","direction":"Benefit shown","population":"Adults 65+; healthy older adults during bed rest","dose_studied":"3 g/day","summary":"Meta-analysis of 7 RCTs in adults 65+ (n=287) shows greater muscle mass with HMB (SMD 0.35) and no change in fat mass; a bed-rest RCT found 3 g/day prevented the ~2 kg lean-mass loss seen with placebo over 10 days. Consistent but modest and small-n; strength/function effects unproven.","caveat":"Borderline grade: consistent direction but modest effects in small samples; strength and function benefits are unproven.","citation_title":"Effect of beta-hydroxy-beta-methylbutyrate supplementation on muscle loss in older adults: a systematic review and meta-analysis.","journal":"Archives of Gerontology and Geriatrics","year":2015,"pmid":"26169182","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/26169182/","study_type":"meta-analysis","sample":"7 RCTs, 287 participants","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"beta-alanine","url":"https://impower.life/evidence#beta-alanine","compound":"Beta-alanine","compound_full":"Beta-alanine","compound_group":"Derivative","outcome":"High-intensity exercise capacity (0.5-10 min efforts)","situations":"Performance","grade":5,"grade_label":"Strong","direction":"Benefit shown","population":"Healthy adults, trained and untrained","dose_studied":"Chronic ingestion; total dose did not moderate effect in meta-regression","summary":"Meta-analysis of 40 double-blind placebo-controlled studies (n=1461) finds a significant overall effect (ES 0.18) that is largest for exercise capacity tests lasting 0.5-10 min (ES 0.50); an individual-participant-data meta-analysis confirms a group effect on time to exhaustion. Effect is real but small and confined to specific exercise durations.","caveat":"The effect is real but small (pooled effect size 0.18) and confined to efforts lasting roughly 30 seconds to 10 minutes. Performance trials used 3.2 to 6.4 g/day.","citation_title":"β-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis.","journal":"British Journal of Sports Medicine","year":2017,"pmid":"27797728","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/27797728/","study_type":"meta-analysis","sample":"40 studies, 1461 participants","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"citrulline-performance","url":"https://impower.life/evidence#citrulline-performance","compound":"Citrulline","compound_full":"Citrulline / citrulline malate","compound_group":"Conditional","outcome":"High-intensity strength and power performance","situations":"Performance","grade":3,"grade_label":"Promising","direction":"Mixed results","population":"Healthy trained men and women","dose_studied":">=3 g citrulline (commonly 8 g citrulline malate) 30-60 min pre-exercise","summary":"Meta-analysis of 12 studies (n=198) finds a small significant benefit (SMD 0.20) with every individual trial's CI crossing zero; a 2021 critical review concludes citrulline malate's efficacy 'remains ambiguous' given equivocal results and product quality problems. Mixed, leaning slightly positive.","caveat":"","citation_title":"Acute Effects of Citrulline Supplementation on High-Intensity Strength and Power Performance: A Systematic Review and Meta-Analysis.","journal":"Sports Medicine","year":2019,"pmid":"30895562","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/30895562/","study_type":"meta-analysis","sample":"12 studies, 198 participants","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"citrulline-bp","url":"https://impower.life/evidence#citrulline-bp","compound":"Citrulline","compound_full":"Citrulline","compound_group":"Conditional","outcome":"Blood pressure","situations":"Heart and circulation","grade":1,"grade_label":"No evidence or conflicting","direction":"No effect or untested","population":"Adults in clinical trials (mixed weight status)","dose_studied":"Not pooled in abstract","summary":"Meta-analysis of 5 clinical trials found no significant change in brachial or aortic systolic or diastolic blood pressure with L-citrulline. Tested; no effect shown.","caveat":"","citation_title":"Effect of L-Citrulline Supplementation on Blood Pressure: a Systematic Review and Meta-Analysis of Clinical Trials.","journal":"Current Hypertension Reports","year":2018,"pmid":"30284051","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/30284051/","study_type":"meta-analysis","sample":"5 interventions","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"arginine-bp","url":"https://impower.life/evidence#arginine-bp","compound":"Arginine","compound_full":"Arginine","compound_group":"Conditional","outcome":"Blood pressure","situations":"Heart and circulation","grade":5,"grade_label":"Strong","direction":"Benefit shown","population":"Adults, normotensive and hypertensive","dose_studied":"4-24 g/day; >=4 g/day effective for SBP","summary":"Two meta-analyses a decade apart agree: 22 RCTs (2022) show SBP -6.4 / DBP -2.6 mmHg with an effective dose >=4 g/day; 11 RCTs (2011, n=387) showed -5.4 / -2.7 mmHg. Consistent direction and magnitude across normotensive and hypertensive adults.","caveat":"","citation_title":"Effect of l-Arginine Supplementation on Blood Pressure in Adults: A Systematic Review and Dose-Response Meta-analysis of Randomized Clinical Trials.","journal":"Advances in Nutrition","year":2022,"pmid":"34967840","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/34967840/","study_type":"meta-analysis","sample":"22 RCTs, 30 effect sizes","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"arginine-endothelial","url":"https://impower.life/evidence#arginine-endothelial","compound":"Arginine","compound_full":"Arginine","compound_group":"Conditional","outcome":"Endothelial function (flow-mediated dilation)","situations":"Heart and circulation","grade":4,"grade_label":"Good","direction":"Mixed results","population":"Adults; benefit limited to those with impaired baseline FMD","dose_studied":"Short-term oral arginine (doses varied)","summary":"Meta-analysis of 12 short-term RCTs (n=492) shows arginine increases FMD by ~2 percentage points, but only in people whose baseline FMD is impaired (<7%); no effect when baseline FMD is normal. Consistent but conditional on baseline dysfunction.","caveat":"","citation_title":"Increase in fasting vascular endothelial function after short-term oral L-arginine is effective when baseline flow-mediated dilation is low: a meta-analysis of randomized controlled trials.","journal":"American Journal of Clinical Nutrition","year":2009,"pmid":"19056561","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/19056561/","study_type":"meta-analysis","sample":"12 studies, 492 participants","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"arginine-post-mi","url":"https://impower.life/evidence#arginine-post-mi","compound":"Arginine","compound_full":"Arginine","compound_group":"Conditional","outcome":"Recovery after acute myocardial infarction (safety signal)","situations":"Heart and circulation","grade":1,"grade_label":"No evidence or conflicting","direction":"Harm signal","population":"Patients after first ST-elevation myocardial infarction","dose_studied":"3 g three times daily (9 g/day) for 6 months","summary":"In a randomized placebo-controlled trial of 153 post-STEMI patients, 9 g/day arginine did not improve vascular stiffness or ejection fraction and 6 patients (8.6%) on arginine died versus none on placebo; the safety board halted enrolment. Tested and harmful in this population.","caveat":"Carry this safety signal onto any arginine claim: enrolment was halted after excess deaths in the arginine arm.","citation_title":"L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial.","journal":"JAMA","year":2006,"pmid":"16391217","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/16391217/","study_type":"RCT","sample":"153","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"arginine-ed","url":"https://impower.life/evidence#arginine-ed","compound":"Arginine","compound_full":"Arginine","compound_group":"Conditional","outcome":"Erectile dysfunction (mild to moderate)","situations":"Other","grade":4,"grade_label":"Good","direction":"Benefit shown","population":"Men with mild to moderate erectile dysfunction","dose_studied":"1,500-5,000 mg/day","summary":"Meta-analysis of 10 RCTs (n=540) finds arginine 1.5-5 g/day improved ED versus placebo (OR 3.37) and raised IIEF erectile-function and satisfaction scores; heterogeneity in dose and duration, and some trials combined arginine with other agents.","caveat":"","citation_title":"The Potential Role of Arginine Supplements on Erectile Dysfunction: A Systemic Review and Meta-Analysis.","journal":"Journal of Sexual Medicine","year":2019,"pmid":"30770070","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/30770070/","study_type":"meta-analysis","sample":"10 RCTs, 540 patients","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"arginine-wound","url":"https://impower.life/evidence#arginine-wound","compound":"Arginine","compound_full":"Arginine (and arginine + HMB + glutamine)","compound_group":"Conditional","outcome":"Wound collagen deposition / healing","situations":"Recovery","grade":3,"grade_label":"Promising","direction":"Benefit shown","population":"Healthy volunteers, including elderly (65+ / 70+)","dose_studied":"17-25 g/day free arginine; or 14 g arginine + 3 g HMB + 14 g glutamine","summary":"Three small randomized trials in healthy volunteers using implanted PTFE catheters consistently show oral arginine (17-25 g/day free arginine) or an arginine/HMB/glutamine mix increases wound hydroxyproline (collagen) deposition; epithelialization was unchanged and outcomes are surrogates, not clinical wound closure.","caveat":"","citation_title":"Arginine stimulates wound healing and immune function in elderly human beings.","journal":"Surgery","year":1993,"pmid":"8342121","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/8342121/","study_type":"RCT","sample":"45","supporting_citations":2,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"immunonutrition-surgery","url":"https://impower.life/evidence#immunonutrition-surgery","compound":"Arginine","compound_full":"Arginine (in immunonutrition formulas with omega-3 and nucleotides)","compound_group":"Conditional","outcome":"Post-surgical infections and length of stay (GI cancer surgery)","situations":"Recovery","grade":4,"grade_label":"Good","direction":"Benefit shown","population":"Patients undergoing elective gastrointestinal cancer surgery","dose_studied":"Commercial immunonutrition formulas (arginine dose varies by product)","summary":"Meta-analysis of 19 RCTs (n=2331) shows perioperative immunonutrition cut infectious complications (RR 0.44) and hospital stay (-2.6 days); an independent systematic review of arginine-supplemented diets reached the same direction. Caveat: formulas are multi-ingredient, so the effect cannot be attributed to arginine alone.","caveat":"Drover 2011 is cited for its metadata only; the PubMed record carries no abstract, so no effect size is attributed to it.","citation_title":"Perioperative immunonutrition for gastrointestinal cancer: a systematic review of randomized controlled trials.","journal":"Surgical Oncology","year":2012,"pmid":"22317969","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/22317969/","study_type":"meta-analysis","sample":"19 RCTs, 2331 patients","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"glutamine-critical-illness","url":"https://impower.life/evidence#glutamine-critical-illness","compound":"Glutamine","compound_full":"Glutamine","compound_group":"Conditional","outcome":"Mortality and recovery in critical illness and severe burns","situations":"Recovery","grade":1,"grade_label":"No evidence or conflicting","direction":"Harm signal","population":"Mechanically ventilated ICU patients with multi-organ failure; severe burn patients","dose_studied":"IV + enteral glutamine (REDOXS); 0.5 g/kg/day enteral (burns)","summary":"Two large NEJM RCTs: in 1223 ICU patients with multi-organ failure, early glutamine was associated with higher in-hospital and 6-month mortality (28-day OR 1.28); in 1200 severe-burn patients, 0.5 g/kg/day enteral glutamine did not shorten time to discharge alive. High-dose glutamine in the critically ill is harmful or ineffective.","caveat":"","citation_title":"A randomized trial of glutamine and antioxidants in critically ill patients.","journal":"New England Journal of Medicine","year":2013,"pmid":"23594003","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/23594003/","study_type":"RCT","sample":"1223","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"glutamine-ibs","url":"https://impower.life/evidence#glutamine-ibs","compound":"Glutamine","compound_full":"Glutamine","compound_group":"Conditional","outcome":"Post-infectious diarrhoea-predominant IBS symptoms","situations":"Gut","grade":3,"grade_label":"Promising","direction":"Benefit shown","population":"Adults with post-infectious IBS-D and increased intestinal permeability","dose_studied":"5 g three times daily for 8 weeks","summary":"One double-blind RCT (n=106 completers) found 5 g three times daily for 8 weeks achieved the primary endpoint in 79.6% vs 5.8% on placebo and normalised intestinal permeability. Striking effect from a single trial that the authors themselves say needs large-RCT validation.","caveat":"A single trial. The authors themselves say the result needs validation in a large RCT before it should change practice.","citation_title":"Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome.","journal":"Gut","year":2019,"pmid":"30108163","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/30108163/","study_type":"RCT","sample":"106 completers","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"glutamine-gut-athletes","url":"https://impower.life/evidence#glutamine-gut-athletes","compound":"Glutamine","compound_full":"Glutamine","compound_group":"Conditional","outcome":"Exercise-induced intestinal permeability (running in heat)","situations":"Gut","grade":2,"grade_label":"Slight","direction":"Benefit shown","population":"Recreationally active men","dose_studied":"0.25, 0.5 or 0.9 g/kg fat-free mass, 2 h pre-exercise","summary":"Single crossover trial in 10 men: acute glutamine (0.25-0.9 g/kg fat-free mass) dose-dependently lowered the lactulose:rhamnose permeability ratio during a 60-min hot run; no effect on GI symptoms. Mechanistic surrogate, very small n.","caveat":"","citation_title":"Glutamine supplementation reduces markers of intestinal permeability during running in the heat in a dose-dependent manner.","journal":"European Journal of Applied Physiology","year":2017,"pmid":"29058112","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/29058112/","study_type":"RCT","sample":"10 (crossover)","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"glutamine-infection-athletes","url":"https://impower.life/evidence#glutamine-infection-athletes","compound":"Glutamine","compound_full":"Glutamine","compound_group":"Conditional","outcome":"Self-reported infections after prolonged exhaustive exercise","situations":"Gut","grade":2,"grade_label":"Slight","direction":"Benefit shown","population":"Marathon/ultramarathon runners and elite rowers","dose_studied":"Two glutamine drinks (immediately and 2 h post-exercise; dose not in abstract)","summary":"One 1996 controlled trial (n=151 questionnaires) reported 81% of glutamine-drink athletes vs 49% of placebo were infection-free in the week after marathons/rowing; outcome was self-reported and the study is old and unreplicated at scale.","caveat":"","citation_title":"Does glutamine have a role in reducing infections in athletes?","journal":"European Journal of Applied Physiology and Occupational Physiology","year":1996,"pmid":"8803512","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/8803512/","study_type":"RCT","sample":"151","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"hmb-arg-gln-cachexia","url":"https://impower.life/evidence#hmb-arg-gln-cachexia","compound":"HMB","compound_full":"HMB + arginine + glutamine","compound_group":"Derivative","outcome":"Fat-free mass in cancer cachexia","situations":"Recovery","grade":3,"grade_label":"Promising","direction":"Benefit shown","population":"Advanced (stage IV) cancer patients with weight loss","dose_studied":"3 g HMB + 14 g arginine + 14 g glutamine per day","summary":"Double-blind RCT in stage IV cancer patients with >=5% weight loss: the HMB/Arg/Gln group gained 1.12 kg fat-free mass at 4 weeks while controls lost 1.34 kg, maintained over 24 weeks by intent-to-treat. Single trial, n=32 evaluable at 4 weeks.","caveat":"","citation_title":"Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine.","journal":"American Journal of Surgery","year":2002,"pmid":"11975938","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/11975938/","study_type":"RCT","sample":"32 evaluable at 4 weeks","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"glycine-sleep","url":"https://impower.life/evidence#glycine-sleep","compound":"Glycine","compound_full":"Glycine","compound_group":"Conditional","outcome":"Sleep quality and next-day fatigue","situations":"Mood and sleep","grade":3,"grade_label":"Promising","direction":"Benefit shown","population":"Healthy adults with sleep complaints or acute sleep restriction","dose_studied":"3 g before bedtime","summary":"A 2026 scoping review identified only 3 glycine sleep trials, all reporting benefit on at least one sleep outcome; the indexed RCT shows 3 g at bedtime reduced fatigue and improved psychomotor vigilance after sleep restriction. Few trials, small samples, authors affiliated with the manufacturer.","caveat":"Few trials, small samples, and authors affiliated with the manufacturer. Two frequently cited glycine sleep trials (2006, 2007) are not indexed in PubMed and are deliberately not used.","citation_title":"The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers.","journal":"Frontiers in Neurology","year":2012,"pmid":"22529837","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/22529837/","study_type":"RCT","sample":"not stated in abstract","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"tryptophan-sleep","url":"https://impower.life/evidence#tryptophan-sleep","compound":"Tryptophan","compound_full":"Tryptophan","compound_group":"Essential","outcome":"Sleep quality","situations":"Mood and sleep","grade":3,"grade_label":"Promising","direction":"Mixed results","population":"Adults (mixed healthy and sleep-disturbed)","dose_studied":">=1 g/day","summary":"Meta-analysis (4 studies quantitatively pooled from 18 identified) shows tryptophan shortens wake-after-sleep-onset, more so at >=1 g/day, but did not affect other sleep components. Positive on one metric only, small evidence base.","caveat":"","citation_title":"The impact of tryptophan supplementation on sleep quality: a systematic review, meta-analysis, and meta-regression.","journal":"Nutrition Reviews","year":2022,"pmid":"33942088","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/33942088/","study_type":"meta-analysis","sample":"4 articles pooled (18 reviewed)","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"tryptophan-mood","url":"https://impower.life/evidence#tryptophan-mood","compound":"Tryptophan","compound_full":"Tryptophan","compound_group":"Essential","outcome":"Mood and anxiety in healthy adults","situations":"Mood and sleep","grade":3,"grade_label":"Promising","direction":"Mixed results","population":"Healthy adults","dose_studied":"0.14-3 g/day","summary":"Systematic review of 11 RCTs: 4 showed reduced negative feelings or increased positive mood with 0.14-3 g/day tryptophan; no effect on aggression; the authors call for better-designed trials. Mixed, leaning positive.","caveat":"","citation_title":"A systematic review of the effect of L-tryptophan supplementation on mood and emotional functioning.","journal":"Journal of Dietary Supplements","year":2021,"pmid":"32272859","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/32272859/","study_type":"systematic review","sample":"11 RCTs","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"5htp-depression","url":"https://impower.life/evidence#5htp-depression","compound":"5-HTP","compound_full":"5-HTP (and tryptophan)","compound_group":"Derivative","outcome":"Depression","situations":"Mood and sleep","grade":2,"grade_label":"Slight","direction":"Benefit shown","population":"Adults with unipolar depression or dysthymia","dose_studied":"Varied; not pooled","summary":"Cochrane found only 2 of 108 trials (n=64) met quality criteria; they favoured 5-HTP/tryptophan over placebo but evidence was 'insufficient quality to be conclusive'. A 2020 meta-analysis reports a 65% remission rate and large effect but rates the studies weak (few placebo controls, I2 76%). Positive signal built on low-quality trials; eosinophilia-myalgia safety history unresolved.","caveat":"","citation_title":"Effects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis.","journal":"Nutrition Reviews","year":2020,"pmid":"31504850","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/31504850/","study_type":"meta-analysis","sample":"13 studies reviewed, 7 pooled","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"theanine-stress","url":"https://impower.life/evidence#theanine-stress","compound":"L-theanine","compound_full":"L-theanine","compound_group":"Derivative","outcome":"Stress and anxiety","situations":"Mood and sleep","grade":3,"grade_label":"Promising","direction":"Benefit shown","population":"Healthy adults exposed to stress","dose_studied":"200-400 mg/day","summary":"Systematic review of 9 RCTs suggests 200-400 mg/day may reduce stress and anxiety in people under stressful conditions; a 4-week crossover RCT (n=30) found lower depression, trait-anxiety and sleep-quality scores. Consistent but small trials and short duration; the review calls for larger, longer studies.","caveat":"","citation_title":"The Effects of Green Tea Amino Acid L-Theanine Consumption on the Ability to Manage Stress and Anxiety Levels: a Systematic Review.","journal":"Plant Foods for Human Nutrition","year":2020,"pmid":"31758301","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/31758301/","study_type":"systematic review","sample":"9 RCTs","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"nac-depression","url":"https://impower.life/evidence#nac-depression","compound":"NAC","compound_full":"N-acetylcysteine (NAC)","compound_group":"Derivative","outcome":"Depressive symptoms (adjunctive, psychiatric populations)","situations":"Mood and sleep","grade":4,"grade_label":"Good","direction":"Benefit shown","population":"Adults with depressive symptoms in bipolar disorder, MDD, trichotillomania, heavy smoking","dose_studied":"Not pooled in abstract","summary":"Meta-analysis of 5 double-blind placebo-controlled RCTs (n=574, 12-24 weeks) shows NAC improved depressive symptoms (SMD 0.37) and global functioning with only minor adverse events. Moderate effect, consistent, but trials were in bipolar/MDD/other psychiatric patients as add-on therapy.","caveat":"","citation_title":"N-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis.","journal":"Journal of Clinical Psychiatry","year":2016,"pmid":"27137430","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/27137430/","study_type":"meta-analysis","sample":"5 RCTs, 574 participants","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"nac-influenza","url":"https://impower.life/evidence#nac-influenza","compound":"NAC","compound_full":"N-acetylcysteine (NAC)","compound_group":"Derivative","outcome":"Influenza-like illness frequency and severity","situations":"Gut","grade":3,"grade_label":"Promising","direction":"Benefit shown","population":"Adults, 78% aged 65+, without chronic respiratory disease","dose_studied":"600 mg twice daily for 6 months","summary":"One randomized double-blind multicentre trial (n=262, mostly 65+) found 600 mg twice daily for 6 months reduced frequency and severity of influenza-like episodes; only 25% of virus-infected NAC subjects became symptomatic vs 79% on placebo. Single, old, unreplicated trial with a large effect.","caveat":"","citation_title":"Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment.","journal":"European Respiratory Journal","year":1997,"pmid":"9230243","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/9230243/","study_type":"RCT","sample":"262","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"nac-acetaminophen","url":"https://impower.life/evidence#nac-acetaminophen","compound":"NAC","compound_full":"N-acetylcysteine (NAC)","compound_group":"Derivative","outcome":"Liver protection after acetaminophen overdose","situations":"Other","grade":5,"grade_label":"Strong","direction":"Benefit shown","population":"Patients with acetaminophen overdose","dose_studied":"140 mg/kg loading then 70 mg/kg every 4 h x17 doses (medical protocol)","summary":"Analysis of 2,540 overdose patients treated with the oral NAC protocol: hepatotoxicity 6.1% when started within 10 h vs 26.4% at 10-24 h, with 0.43% mortality; NAC is the established antidote. Note this is medical treatment at pharmacological doses, not supplement use.","caveat":"Hospital treatment of overdose at pharmacological doses under medical supervision. Not a supplement use and not transferable to supplement doses.","citation_title":"Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985).","journal":"New England Journal of Medicine","year":1988,"pmid":"3059186","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/3059186/","study_type":"cohort","sample":"2540","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"nac-nafld","url":"https://impower.life/evidence#nac-nafld","compound":"NAC","compound_full":"N-acetylcysteine (NAC)","compound_group":"Derivative","outcome":"Liver enzymes in non-alcoholic fatty liver disease","situations":"Other","grade":2,"grade_label":"Slight","direction":"Benefit shown","population":"Adults with NAFLD","dose_studied":"Not stated in abstract","summary":"Single small trial (n=30) comparing NAC with vitamin C found a significant ALT reduction at 3 months; no placebo arm, no histology, short follow-up.","caveat":"","citation_title":"N-acetylcysteine improves liver function in patients with non-alcoholic Fatty liver disease.","journal":"Hepatitis Monthly","year":2010,"pmid":"22308119","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/22308119/","study_type":"RCT","sample":"30","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"glycine-nafld","url":"https://impower.life/evidence#glycine-nafld","compound":"Glycine","compound_full":"Glycine","compound_group":"Conditional","outcome":"Non-alcoholic fatty liver disease","situations":"Other","grade":2,"grade_label":"Slight","direction":"Benefit shown","population":"Mice with diet-induced NASH; human liver tissue (observational)","dose_studied":"Not applicable (preclinical)","summary":"Human liver transcriptomics show suppressed glycine synthesis in NAFLD and a glycine-based tripeptide reversed steatohepatitis in mice, but there is no human supplementation trial; the paper itself says clinical evaluation is warranted. Mechanistic and animal-heavy.","caveat":"Primarily a preclinical, mechanistic study recorded as a cohort for schema compatibility. Not human efficacy evidence.","citation_title":"Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome.","journal":"Science Translational Medicine","year":2020,"pmid":"33268508","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/33268508/","study_type":"cohort","sample":"preclinical plus human tissue","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"bcaa-hepatic-encephalopathy","url":"https://impower.life/evidence#bcaa-hepatic-encephalopathy","compound":"BCAAs","compound_full":"BCAAs (leucine, isoleucine, valine)","compound_group":"Essential","outcome":"Hepatic encephalopathy in cirrhosis","situations":"Other","grade":4,"grade_label":"Good","direction":"Benefit shown","population":"Adults with cirrhosis and overt or covert hepatic encephalopathy","dose_studied":"Oral (10 trials) or intravenous (8 trials) BCAA; doses varied","summary":"2026 Cochrane update of 18 RCTs (n=934) finds BCAAs reduce hepatic encephalopathy (RR 0.79, low-certainty evidence) with no effect on mortality (very low certainty) and possibly more nausea/diarrhoea. A real but low-certainty benefit in a specific clinical population.","caveat":"","citation_title":"Branched-chain amino acids for people with cirrhosis and hepatic encephalopathy.","journal":"Cochrane Database of Systematic Reviews","year":2026,"pmid":"41542879","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/41542879/","study_type":"meta-analysis","sample":"18 trials, 934 participants","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"tyrosine-cognition","url":"https://impower.life/evidence#tyrosine-cognition","compound":"Tyrosine","compound_full":"Tyrosine","compound_group":"Conditional","outcome":"Cognitive performance under acute stress","situations":"Mood and sleep","grade":3,"grade_label":"Promising","direction":"Benefit shown","population":"Healthy adults under acute psychological/physical stress (e.g. military cadets)","dose_studied":"2 g per dose, five daily doses (cadet trial)","summary":"Narrative review concludes tyrosine enhances cognition specifically in short-term stressful or cognitively demanding situations when catecholamines are depleted, with little value for clinical disorders or physical performance; a cadet RCT (n=21) found better memory/tracking performance and lower SBP during combat training. Consistent mechanism, small trials.","caveat":"","citation_title":"Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands--A review.","journal":"Journal of Psychiatric Research","year":2015,"pmid":"26424423","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/26424423/","study_type":"systematic review","sample":"narrative review","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"lysine-herpes","url":"https://impower.life/evidence#lysine-herpes","compound":"Lysine","compound_full":"Lysine","compound_group":"Essential","outcome":"Prevention of herpes simplex labialis (cold sores)","situations":"Other","grade":1,"grade_label":"No evidence or conflicting","direction":"Mixed results","population":"Immunocompetent adults with recurrent herpes simplex","dose_studied":"1 g three times daily (3 g/day) in the positive 1987 trial","summary":"The 2015 Cochrane review of 32 RCTs 'failed to find any evidence of efficacy for lysine' in preventing cold sores. A 1987 trial (n=52) reported fewer and milder recurrences at 3 g/day, and a 2017 review says doses under 1 g/day are ineffective while >3 g/day may improve subjective experience. Conflicting, with the highest-quality synthesis negative.","caveat":"","citation_title":"Interventions for prevention of herpes simplex labialis (cold sores on the lips).","journal":"Cochrane Database of Systematic Reviews","year":2015,"pmid":"26252373","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/26252373/","study_type":"systematic review","sample":"32 RCTs, 2640 participants (all interventions)","supporting_citations":2,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"lysine-anxiety","url":"https://impower.life/evidence#lysine-anxiety","compound":"Lysine","compound_full":"Lysine","compound_group":"Essential","outcome":"Anxiety and stress response","situations":"Mood and sleep","grade":2,"grade_label":"Slight","direction":"Benefit shown","population":"Families in economically weak communities consuming wheat as staple (NW Syria)","dose_studied":"Lysine fortification of wheat flour (dose not in abstract)","summary":"A 3-month randomized double-blind trial of lysine-fortified wheat in low-income Syrian families reduced cortisol stress response (females), sympathetic arousal (males) and trait anxiety (males). Single trial in a lysine-deficient population eating wheat-based diets; not generalisable to supplemented Western adults.","caveat":"","citation_title":"Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria.","journal":"Proceedings of the National Academy of Sciences of the United States of America","year":2004,"pmid":"15159538","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/15159538/","study_type":"RCT","sample":"not stated in abstract","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"taurine-bp","url":"https://impower.life/evidence#taurine-bp","compound":"Taurine","compound_full":"Taurine","compound_group":"Conditional","outcome":"Blood pressure","situations":"Heart and circulation","grade":4,"grade_label":"Good","direction":"Benefit shown","population":"Adults at risk of or with metabolic syndrome; mixed health status","dose_studied":"0.5-6 g/day","summary":"Meta-analysis of 25 RCTs (n=1024) shows SBP -4.0 / DBP -1.5 mmHg with a dose-dependent DBP effect; an earlier meta-analysis of 7 studies (n=103) found ~3 mmHg reductions. Consistent direction; the larger analysis pooled metabolic-syndrome-related trials rather than hypertension trials specifically.","caveat":"","citation_title":"Taurine reduces the risk for metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials.","journal":"Nutrition & Diabetes","year":2024,"pmid":"38755142","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/38755142/","study_type":"meta-analysis","sample":"25 RCTs, 1024 participants","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"taurine-endurance","url":"https://impower.life/evidence#taurine-endurance","compound":"Taurine","compound_full":"Taurine","compound_group":"Conditional","outcome":"Endurance exercise performance","situations":"Performance","grade":3,"grade_label":"Promising","direction":"Benefit shown","population":"Healthy adults, varied training status","dose_studied":"1-6 g single dose or up to 2 weeks","summary":"Meta-analysis of 10 studies shows a moderate improvement in endurance performance (Hedges' g 0.40) including time-to-exhaustion, with no dose or acute-vs-chronic effect. Only one meta-analysis, built on small trials.","caveat":"","citation_title":"The Effects of an Oral Taurine Dose and Supplementation Period on Endurance Exercise Performance in Humans: A Meta-Analysis.","journal":"Sports Medicine","year":2018,"pmid":"29546641","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/29546641/","study_type":"meta-analysis","sample":"10 studies","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"taurine-heart-failure","url":"https://impower.life/evidence#taurine-heart-failure","compound":"Taurine","compound_full":"Taurine","compound_group":"Conditional","outcome":"Heart failure symptoms and function","situations":"Heart and circulation","grade":2,"grade_label":"Slight","direction":"Benefit shown","population":"Patients with congestive heart failure (NYHA II-III)","dose_studied":"500 mg three times daily (2017); 1985 dose not in abstract","summary":"A 1985 double-blind crossover trial in 14 CHF patients improved NYHA class and clinical signs over 4 weeks; a 2017 small RCT showed reduced inflammatory and atherogenic indices with 1.5 g/day. Very small, old, and surrogate-heavy; no outcome trials.","caveat":"A companion paper from the same group (Ahmadian 2017, PMID 28118062) is flagged retracted in PubMed and is excluded from this dataset.","citation_title":"Therapeutic effect of taurine in congestive heart failure: a double-blind crossover trial.","journal":"Clinical Cardiology","year":1985,"pmid":"3888464","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/3888464/","study_type":"RCT","sample":"14 (crossover)","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"taurine-metabolic","url":"https://impower.life/evidence#taurine-metabolic","compound":"Taurine","compound_full":"Taurine","compound_group":"Conditional","outcome":"Glycemic control and lipids in overweight/obesity","situations":"Metabolic","grade":4,"grade_label":"Good","direction":"Benefit shown","population":"Adults with overweight or obesity; adults with metabolic-syndrome risk","dose_studied":"0.5-6 g/day; 3 g/day most effective","summary":"Meta-analysis of 9 RCTs in overweight/obese adults shows lower fasting insulin (-2.15 uU/mL), triglycerides and total cholesterol, with HbA1c (-0.33%) and HOMA-IR improving in obese participants and at 3 g/day; a second meta-analysis (25 RCTs) confirms lower fasting glucose and triglycerides. Consistent, modest effects.","caveat":"","citation_title":"Effect of Long-Term Taurine Supplementation on the Lipid and Glycaemic Profile in Adults with Overweight or Obesity: A Systematic Review and Meta-Analysis.","journal":"Nutrients","year":2024,"pmid":"39796489","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/39796489/","study_type":"meta-analysis","sample":"9 RCTs","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"taurine-aging","url":"https://impower.life/evidence#taurine-aging","compound":"Taurine","compound_full":"Taurine","compound_group":"Conditional","outcome":"Aging / healthspan","situations":"Other","grade":2,"grade_label":"Slight","direction":"Benefit shown","population":"Mice, monkeys; humans observational","dose_studied":"Not applicable to humans (animal dosing)","summary":"The Science 2023 paper shows taurine declines with age and supplementation extended healthspan in mice and monkeys and lifespan in mice; in humans the data are correlational only and the authors say clinical trials are warranted. Animal-heavy; no human intervention outcome.","caveat":"Primarily an animal study with correlational human data, recorded as a cohort for schema compatibility.","citation_title":"Taurine deficiency as a driver of aging.","journal":"Science","year":2023,"pmid":"37289866","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/37289866/","study_type":"cohort","sample":"preclinical plus human observational","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"carnitine-cv","url":"https://impower.life/evidence#carnitine-cv","compound":"L-carnitine","compound_full":"L-carnitine","compound_group":"Derivative","outcome":"Secondary prevention after myocardial infarction","situations":"Heart and circulation","grade":3,"grade_label":"Promising","direction":"Mixed results","population":"Patients with acute myocardial infarction","dose_studied":"Not pooled in abstract","summary":"Meta-analysis of 13 controlled trials (n=3629) found a borderline 27% reduction in all-cause mortality (OR 0.73, p=0.05), fewer ventricular arrhythmias and less angina, but no reduction in heart failure or reinfarction; the authors call for modern large RCTs. Mixed, older trials.","caveat":"","citation_title":"L-carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis.","journal":"Mayo Clinic Proceedings","year":2013,"pmid":"23597877","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/23597877/","study_type":"meta-analysis","sample":"13 trials, 3629 participants","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"carnitine-hf","url":"https://impower.life/evidence#carnitine-hf","compound":"L-carnitine","compound_full":"L-carnitine","compound_group":"Derivative","outcome":"Chronic heart failure (cardiac function and symptoms)","situations":"Heart and circulation","grade":4,"grade_label":"Good","direction":"Benefit shown","population":"Patients with chronic heart failure","dose_studied":"Not pooled in abstract","summary":"Meta-analysis of 17 RCTs (n=1625) shows improved LVEF (+4.1%), stroke volume, cardiac output and lower BNP/NT-proBNP, but no difference in all-cause mortality or 6-minute walk. Consistent surrogate improvements; many trials from Chinese databases, so quality is uncertain.","caveat":"","citation_title":"Efficacy and Safety of L-Carnitine Treatment for Chronic Heart Failure: A Meta-Analysis of Randomized Controlled Trials.","journal":"BioMed Research International","year":2017,"pmid":"28497060","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/28497060/","study_type":"meta-analysis","sample":"17 RCTs, 1625 patients","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"carnitine-weight","url":"https://impower.life/evidence#carnitine-weight","compound":"L-carnitine","compound_full":"L-carnitine","compound_group":"Derivative","outcome":"Body weight and fat mass","situations":"Metabolic","grade":4,"grade_label":"Good","direction":"Benefit shown","population":"Adults, especially with overweight/obesity","dose_studied":"2,000 mg/day (maximum effect in dose-response)","summary":"Meta-analysis of 37 RCTs (n=2292) shows modest reductions in body weight (-1.21 kg), BMI and fat mass, maximal at 2 g/day; only the weight effect survived restriction to high-quality trials. Consistent but small.","caveat":"","citation_title":"Effects of l-carnitine supplementation on weight loss and body composition: A systematic review and meta-analysis of 37 randomized controlled clinical trials with dose-response analysis.","journal":"Clinical Nutrition ESPEN","year":2020,"pmid":"32359762","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/32359762/","study_type":"meta-analysis","sample":"37 RCTs, 2292 participants","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"carnitine-glycemic","url":"https://impower.life/evidence#carnitine-glycemic","compound":"L-carnitine","compound_full":"L-carnitine","compound_group":"Derivative","outcome":"Glycemic control and lipids in type 2 diabetes","situations":"Metabolic","grade":4,"grade_label":"Good","direction":"Benefit shown","population":"Adults with type 2 diabetes","dose_studied":"1-4 g/day (U-shaped BMI effect, largest at 2 g/day)","summary":"Dose-response meta-analysis of 21 RCTs (n=2041) shows each 1 g/day lowers HbA1c by 0.16% (GRADE moderate) and LDL by 0.11 mmol/L (GRADE high), with small glucose and triglyceride reductions; heterogeneity is very high and the authors urge caution. Consistent but small effects.","caveat":"","citation_title":"The Effects of L-Carnitine Supplementation on Weight Loss, Glycemic Control, and Cardiovascular Risk Factors in Patients With Type 2 Diabetes: A Systematic Review and Dose-response Meta-Analysis of Randomized Controlled Trials.","journal":"Clinical Therapeutics","year":2024,"pmid":"38594107","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/38594107/","study_type":"meta-analysis","sample":"21 RCTs, 2041 patients","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"carnitine-fatigue-older","url":"https://impower.life/evidence#carnitine-fatigue-older","compound":"L-carnitine","compound_full":"L-carnitine","compound_group":"Derivative","outcome":"Physical and mental fatigue in the very old","situations":"Adults 65+","grade":2,"grade_label":"Slight","direction":"Benefit shown","population":"Centenarians with fatigue after slight activity","dose_studied":"2 g levocarnitine once daily","summary":"One RCT in 66 centenarians reported 2 g/day reduced physical and mental fatigue, increased muscle mass (+3.8 kg) and improved MMSE versus placebo. Single single-centre trial with implausibly large effects; unreplicated.","caveat":"","citation_title":"L-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial.","journal":"American Journal of Clinical Nutrition","year":2007,"pmid":"18065594","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/18065594/","study_type":"RCT","sample":"66","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"leucine-whey-vitd-sarcopenia","url":"https://impower.life/evidence#leucine-whey-vitd-sarcopenia","compound":"Whey + leucine + vit D","compound_full":"Leucine-enriched whey protein + vitamin D (PROVIDE formula)","compound_group":"Essential","outcome":"Sarcopenia measures in older adults","situations":"Adults 65+","grade":4,"grade_label":"Good","direction":"Mixed results","population":"Sarcopenic, primarily independent-living older adults (SPPB 4-9, low muscle mass index)","dose_studied":"Twice-daily supplement (each serving: leucine-enriched whey protein + vitamin D; product-specific)","summary":"The largest sarcopenia nutrition RCT (n=380, 13 weeks) improved appendicular muscle mass (+0.17 kg) and chair-stand time, but the primary outcomes (handgrip strength and SPPB) improved equally in both groups. Large trial, modest and partly null result; supported by leucine meta-analyses in the elderly.","caveat":"","citation_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.","journal":"Journal of the American Medical Directors Association","year":2015,"pmid":"26170041","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/26170041/","study_type":"RCT","sample":"380","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"eaa-older-lean-mass","url":"https://impower.life/evidence#eaa-older-lean-mass","compound":"EAA blend","compound_full":"Essential amino acid blend (EAA)","compound_group":"Essential","outcome":"Lean body mass and function in older adults (including bed rest)","situations":"Adults 65+","grade":3,"grade_label":"Promising","direction":"Benefit shown","population":"Older adults (67-71 y), including bed-rest and glucose-intolerant subjects","dose_studied":"15 g/day; 11 g EAA + arginine twice daily; 16.5 g EAA + 30 g carbohydrate three times daily","summary":"Three small trials from the same research group: 15 g/day EAA for 3 months increased lean mass and basal MPS in older women (n=14, strength unchanged); EAA+arginine for 16 weeks improved lean mass, strength and gait in glucose-intolerant elderly (n=12, no control group); EAA+carbohydrate preserved lean leg mass and strength during 28 days of bed rest. Consistent direction, small samples.","caveat":"","citation_title":"Amino acid supplementation increases lean body mass, basal muscle protein synthesis, and insulin-like growth factor-I expression in older women.","journal":"Journal of Clinical Endocrinology and Metabolism","year":2009,"pmid":"19208731","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/19208731/","study_type":"RCT","sample":"14","supporting_citations":2,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"protein-guidelines-older","url":"https://impower.life/evidence#protein-guidelines-older","compound":"Protein (comparator)","compound_full":"Dietary protein (expert position papers)","compound_group":"Derivative","outcome":"Recommended protein intake to maintain muscle in adults 65+","situations":"Adults 65+","grade":4,"grade_label":"Good","direction":"Benefit shown","population":"Adults over 65","dose_studied":"1.0-1.2 g protein/kg/day (healthy); 1.2-1.5 g/kg/day (acute or chronic illness)","summary":"Two independent expert groups (PROT-AGE 2013; ESPEN 2014) reviewed the evidence and both recommend 1.0-1.2 g/kg/day for healthy older adults, 1.2-1.5 g/kg/day when ill or malnourished, plus resistance/aerobic exercise; both note evidence is insufficient for specific recommendations on protein quality, timing or supplements.","caveat":"","citation_title":"Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group.","journal":"Journal of the American Medical Directors Association","year":2013,"pmid":"23867520","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/23867520/","study_type":"position paper","sample":"consensus","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"protein-weight-loss-lean-mass","url":"https://impower.life/evidence#protein-weight-loss-lean-mass","compound":"Protein (comparator)","compound_full":"Higher-protein diet (comparator; indirect evidence for the GLP-1 segment)","compound_group":"Derivative","outcome":"Lean-mass preservation during caloric restriction","situations":"Eating less (small appetites)","grade":5,"grade_label":"Strong","direction":"Benefit shown","population":"Adults and older adults undergoing diet-induced weight loss (no GLP-1 therapy)","dose_studied":">=25% energy from protein or >=1.0 g/kg/day; up to 2.4 g/kg/day with intense training","summary":"Meta-analysis of 24 RCTs (n=1063) shows energy-restricted high-protein diets mitigate fat-free-mass loss (+0.43 kg) and REE decline versus standard protein; a meta-analysis of 20 RCTs in adults 50+ finds more lean-mass retention with higher protein; a 4-week RCT with 2.4 vs 1.2 g/kg/day during a 40% deficit plus training produced +1.2 vs +0.1 kg lean mass. Consistent, but none of these trials involved GLP-1 drugs.","caveat":"Indirect evidence for the GLP-1 situation: these are diet-only weight-loss trials with no GLP-1 medication involved.","citation_title":"Effects of energy-restricted high-protein, low-fat compared with standard-protein, low-fat diets: a meta-analysis of randomized controlled trials.","journal":"American Journal of Clinical Nutrition","year":2012,"pmid":"23097268","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/23097268/","study_type":"meta-analysis","sample":"24 trials, 1063 individuals","supporting_citations":2,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"whey-leucine-vitd-weight-loss-older","url":"https://impower.life/evidence#whey-leucine-vitd-weight-loss-older","compound":"Whey + leucine + vit D","compound_full":"Whey protein + leucine + vitamin D supplement","compound_group":"Essential","outcome":"Muscle preservation during intentional weight loss in obese older adults","situations":"Eating less (small appetites)","grade":3,"grade_label":"Promising","direction":"Benefit shown","population":"Obese older adults (mean 63 y, BMI 33) on a hypocaloric diet with resistance training","dose_studied":"21 g protein per serving, 10 servings/week (leucine- and vitamin D-enriched)","summary":"Double-blind RCT (n=80, 13 weeks, -600 kcal/day diet plus resistance training): appendicular muscle mass changed +0.4 kg with the supplement vs -0.5 kg with isocaloric control, with equal weight and fat loss; strength and function did not differ. Single well-run trial; diet-induced, not drug-induced, weight loss.","caveat":"Indirect evidence for the GLP-1 situation: diet-induced weight loss, no GLP-1 medication involved.","citation_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.","journal":"American Journal of Clinical Nutrition","year":2015,"pmid":"25646324","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/25646324/","study_type":"RCT","sample":"80","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"eaa-caloric-restriction-older","url":"https://impower.life/evidence#eaa-caloric-restriction-older","compound":"EAA blend","compound_full":"Essential amino acid blend (EAA) + whey meal replacement","compound_group":"Essential","outcome":"Lean-mass preservation during caloric restriction in obese elderly","situations":"Eating less (small appetites)","grade":2,"grade_label":"Slight","direction":"Mixed results","population":"Elderly obese adults on an 1200 kcal/day diet","dose_studied":"800 kcal/day EAA/whey meal replacements (EAA dose not in abstract)","summary":"Small RCT (n=12, 8 weeks, 7% weight loss): the EAA/whey meal replacement did not significantly preserve lean tissue versus a competitor product but produced greater fat loss and higher acute MPS. Tiny sample; mixed result.","caveat":"Indirect evidence for the GLP-1 situation: caloric restriction without medication, and a tiny sample.","citation_title":"Whey protein and essential amino acids promote the reduction of adipose tissue and increased muscle protein synthesis during caloric restriction-induced weight loss in elderly, obese individuals.","journal":"Nutrition Journal","year":2012,"pmid":"23231757","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/23231757/","study_type":"RCT","sample":"12","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"eaa-glp1-direct","url":"https://impower.life/evidence#eaa-glp1-direct","compound":"EAA blend","compound_full":"Essential amino acids / protein supplementation","compound_group":"Essential","outcome":"Lean-mass preservation during GLP-1 medication","situations":"Eating less (small appetites)","grade":1,"grade_label":"No evidence or conflicting","direction":"No effect or untested","population":"Adults with obesity on GLP-1 medication","dose_studied":"None tested directly yet (two trials registered); reviews suggest 1.2-2.0 g protein/kg/day by extrapolation","summary":"No completed randomized trial of EAA, leucine, or protein supplementation in GLP-1-treated patients with a lean-mass outcome was found on PubMed or ClinicalTrials.gov as of 2026-10-22. Two registered trials will test it: LEAN-PREP (NCT06885736; protein plus resistance exercise during semaglutide or tirzepatide; recruiting, primary completion expected around 2029) and PRESERVE-HMB (NCT07760948; HMB plus vitamin D in older adults starting semaglutide; not yet recruiting). What exists: a 2026 meta-analysis of 7 RCTs (n=821) quantifying lean-mass loss on obesity-dose GLP-1 medication (absolute -1.74 kg; one drug -5.44 kg; lean mass as a proportion of weight actually rises), a 2024 review of mitigation strategies, and a 2025 narrative review recommending protein 1.2-2.0 g/kg/day, creatine and HMB by extrapolation from non-GLP-1 weight-loss trials. Untested, not disproven.","caveat":"Untested, not disproven. The two registered trials named in the summary have no results yet; check the registry entries for status.","citation_title":"Effect of GLP-1 receptor agonists at doses for obesity management on muscle health: systematic review and meta-analysis of randomized controlled trials (RCTs).","journal":"International Journal of Obesity","year":2026,"pmid":"42321502","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/42321502/","study_type":"meta-analysis","sample":"7 RCTs, 821 patients","supporting_citations":3,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"bariatric-protein","url":"https://impower.life/evidence#bariatric-protein","compound":"Protein (comparator)","compound_full":"Protein / amino acid supplementation","compound_group":"Derivative","outcome":"Body composition after bariatric surgery","situations":"After bariatric surgery","grade":3,"grade_label":"Promising","direction":"Mixed results","population":"Adults after metabolic/bariatric surgery","dose_studied":"Daily protein supplement (products and doses varied; pilot reached ~25% of energy from protein)","summary":"Meta-analysis of 10 RCTs: protein supplementation after metabolic bariatric surgery increased muscle mass (+1.33 kg) and fat-free mass (+1.74 kg) with low-certainty evidence, but did not change BMI or lean body mass; a pilot RCT (n=20) showed less lean-mass loss (21% vs 27% of weight lost). Mixed, leaning positive, low certainty.","caveat":"The guideline abstract does not state a protein dose, so none is attributed to it here.","citation_title":"The effects of protein supplementation on body composition after bariatric surgery: a systematic review and meta-analysis of randomized controlled trials.","journal":"Obesity (Silver Spring)","year":2025,"pmid":"40312971","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/40312971/","study_type":"meta-analysis","sample":"10 trials","supporting_citations":2,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"histidine-insulin-resistance","url":"https://impower.life/evidence#histidine-insulin-resistance","compound":"Histidine","compound_full":"Histidine","compound_group":"Essential","outcome":"Insulin resistance and inflammation in obese women with metabolic syndrome","situations":"Metabolic","grade":2,"grade_label":"Slight","direction":"Benefit shown","population":"Obese women (33-51 y) with metabolic syndrome","dose_studied":"4 g/day for 12 weeks","summary":"One randomized double-blind trial (n=100, 92 completers) found 4 g/day for 12 weeks lowered HOMA-IR by 1.09, BMI, waist, fat mass and inflammatory cytokines. Single-centre, unreplicated.","caveat":"","citation_title":"Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial.","journal":"Diabetologia","year":2013,"pmid":"23361591","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/23361591/","study_type":"RCT","sample":"100 (92 completed)","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"methionine","url":"https://impower.life/evidence#methionine","compound":"Methionine","compound_full":"Methionine","compound_group":"Essential","outcome":"Metabolic health (supplementation)","situations":"Metabolic","grade":1,"grade_label":"No evidence or conflicting","direction":"No effect or untested","population":"Obese adults with metabolic syndrome (restriction study)","dose_studied":"Restriction to 2 mg/kg/day vs 35 mg/kg/day (not supplementation)","summary":"No human trial of methionine supplementation for a health outcome was found; the only relevant RCT tests methionine RESTRICTION (n=26), which increased fat oxidation and reduced liver fat without changing insulin sensitivity relative to control. The evidence, such as it is, points away from supplementing.","caveat":"","citation_title":"Dietary methionine restriction increases fat oxidation in obese adults with metabolic syndrome.","journal":"Journal of Clinical Endocrinology and Metabolism","year":2011,"pmid":"21346062","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/21346062/","study_type":"RCT","sample":"26","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"threonine","url":"https://impower.life/evidence#threonine","compound":"Threonine","compound_full":"Threonine","compound_group":"Essential","outcome":"Any health outcome (supplementation)","situations":"Other","grade":1,"grade_label":"No evidence or conflicting","direction":"No effect or untested","population":"Healthy adult men (mean age 43)","dose_studied":"0-12 g/day for 4 weeks (safety only)","summary":"The only recent RCT is a safety/tolerability study establishing a no-observed-adverse-effect level of 12 g/day in healthy men; no efficacy outcomes were measured. No efficacy evidence exists.","caveat":"","citation_title":"Evaluation of safe utilization of L-threonine for supplementation in healthy adults: a randomized double blind controlled trial.","journal":"Amino Acids","year":2025,"pmid":"40419835","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/40419835/","study_type":"RCT","sample":"not stated in abstract (crossover)","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"collagen-joint-pain","url":"https://impower.life/evidence#collagen-joint-pain","compound":"Collagen peptides","compound_full":"Collagen peptides / hydrolysate","compound_group":"Derivative","outcome":"Activity-related joint pain and joint function","situations":"Recovery","grade":4,"grade_label":"Good","direction":"Benefit shown","population":"Recreational and varsity athletes with activity-related joint pain","dose_studied":"10-15 g/day","summary":"Systematic review of 15 RCTs concludes collagen peptides are most beneficial for joint functionality and pain; the founding 24-week RCT in 147 athletes (97 analysed) showed significant reductions in joint pain at rest, walking, standing and lifting with 10 g/day. Consistent across trials, though several are industry-sponsored.","caveat":"","citation_title":"The effects of collagen peptide supplementation on body composition, collagen synthesis, and recovery from joint injury and exercise: a systematic review.","journal":"Amino Acids","year":2021,"pmid":"34491424","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/34491424/","study_type":"systematic review","sample":"15 RCTs","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"collagen-body-comp-older","url":"https://impower.life/evidence#collagen-body-comp-older","compound":"Collagen peptides","compound_full":"Collagen peptides","compound_group":"Derivative","outcome":"Fat-free mass and strength with resistance training in sarcopenic older men","situations":"Adults 65+","grade":3,"grade_label":"Promising","direction":"Benefit shown","population":"Elderly men (mean 72 y) with sarcopenia performing resistance training","dose_studied":"15 g/day post-exercise","summary":"RCT (n=53, 12 weeks of resistance training): 15 g/day collagen peptides increased fat-free mass (+4.2 vs +2.9 kg) and quadriceps strength more than placebo. Single trial with manufacturer co-authorship; in young adults whey outperformed leucine-matched collagen for muscle thickness, and collagen does not raise MPS like higher-quality protein.","caveat":"Single trial with manufacturer co-authorship; a 2025 corrigendum (PMID 40859798) was issued for the primary paper.","citation_title":"Collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men: a randomised controlled trial.","journal":"British Journal of Nutrition","year":2015,"pmid":"26353786","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/26353786/","study_type":"RCT","sample":"53","supporting_citations":1,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"collagen-skin","url":"https://impower.life/evidence#collagen-skin","compound":"Collagen peptides","compound_full":"Hydrolyzed collagen","compound_group":"Derivative","outcome":"Skin hydration, elasticity and wrinkles","situations":"Other","grade":4,"grade_label":"Good","direction":"Benefit shown","population":"Adults 20-70 y, 95% women","dose_studied":"Varied; 90 days of supplementation","summary":"Meta-analysis of 19 randomized double-blind controlled trials (n=1125, 95% women) shows improved hydration, elasticity and wrinkles after ~90 days versus placebo. Consistent, though many trials are manufacturer-funded and outcomes are instrumental skin measures.","caveat":"","citation_title":"Effects of hydrolyzed collagen supplementation on skin aging: a systematic review and meta-analysis.","journal":"International Journal of Dermatology","year":2021,"pmid":"33742704","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/33742704/","study_type":"meta-analysis","sample":"19 studies, 1125 participants","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"gelatin-collagen-synthesis","url":"https://impower.life/evidence#gelatin-collagen-synthesis","compound":"Gelatin","compound_full":"Gelatin / collagen (with vitamin C)","compound_group":"Derivative","outcome":"Collagen synthesis for tendon/ligament injury prevention","situations":"Recovery","grade":2,"grade_label":"Slight","direction":"Benefit shown","population":"Healthy young men","dose_studied":"5 or 15 g gelatin with vitamin C, 1 h before exercise, three times daily","summary":"Crossover trial in 8 men: 15 g vitamin C-enriched gelatin 1 h before rope-skipping doubled a blood marker of collagen synthesis (PINP) and serum improved engineered-ligament mechanics. Mechanistic surrogate in a very small sample; no injury outcomes.","caveat":"","citation_title":"Vitamin C-enriched gelatin supplementation before intermittent activity augments collagen synthesis.","journal":"American Journal of Clinical Nutrition","year":2017,"pmid":"27852613","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/27852613/","study_type":"RCT","sample":"8 (crossover)","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"bcaa-fatigue-markers","url":"https://impower.life/evidence#bcaa-fatigue-markers","compound":"BCAAs","compound_full":"BCAAs (leucine, isoleucine, valine)","compound_group":"Essential","outcome":"Fatigue biomarkers (cortisol, lactate) in exercise recovery","situations":"Performance","grade":2,"grade_label":"Slight","direction":"Mixed results","population":"Trained and untrained adults","dose_studied":"Not pooled in abstract","summary":"Meta-analysis (7 studies for cortisol, n=146; 15 for lactate, n=279) found BCAA lowered post-exercise cortisol and blood lactate, but these are biomarkers rather than performance or endurance outcomes. Surrogate endpoints only.","caveat":"","citation_title":"Peripheral fatigue and hormone responses to branched-chain amino acids ingestion and exercise in recovery: a systematic review and meta-analysis.","journal":"Minerva Endocrinology","year":2024,"pmid":"36177954","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/36177954/","study_type":"meta-analysis","sample":"15 studies, up to 279 participants","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"bcaa-insulin-resistance","url":"https://impower.life/evidence#bcaa-insulin-resistance","compound":"BCAAs","compound_full":"BCAAs (leucine, isoleucine, valine)","compound_group":"Essential","outcome":"Insulin resistance (metabolic safety signal)","situations":"Metabolic","grade":2,"grade_label":"Slight","direction":"Harm signal","population":"Obese vs lean humans (observational); rats (intervention)","dose_studied":"Not applicable (dietary BCAA supplementation in rats)","summary":"Metabolomic profiling links an elevated-BCAA signature to obesity and insulin resistance in humans, and adding BCAA to a high-fat diet made rats as insulin resistant as high-fat alone despite less weight gain. Observational in humans, interventional only in animals; a caution flag, not a proven human harm.","caveat":"","citation_title":"A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance.","journal":"Cell Metabolism","year":2009,"pmid":"19356713","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/19356713/","study_type":"cohort","sample":"human cohort plus rat feeding study","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"},{"id":"arginine-glycemic","url":"https://impower.life/evidence#arginine-glycemic","compound":"Arginine","compound_full":"Arginine","compound_group":"Conditional","outcome":"Glycemic control","situations":"Metabolic","grade":2,"grade_label":"Slight","direction":"Mixed results","population":"Adults in clinical trials (diabetic and non-diabetic)","dose_studied":">6.5 g/day for <=12.8 weeks in the responsive subgroup","summary":"Meta-analysis of 10 RCTs shows statistically significant but tiny reductions in fasting glucose (-3.35 mg/dL) and insulin, with no effect on HOMA-IR or HbA1c; the authors state the clinical importance 'may not be meaningful'. Effect too small to matter.","caveat":"","citation_title":"Effects of l-arginine supplementation on glycemic profile: Evidence from a systematic review and meta-analysis of clinical trials.","journal":"Journal of Integrative Medicine","year":2020,"pmid":"32561357","pubmed_url":"https://pubmed.ncbi.nlm.nih.gov/32561357/","study_type":"meta-analysis","sample":"10 trials","supporting_citations":0,"citations_verified_on":"2026-10-22","rubric_version":"0.2-draft","license":"https://creativecommons.org/licenses/by/4.0/","attribution":"IMPOWERLIFE™, Amino acid evidence chart, https://impower.life/evidence"}]}