The Trial Index
Every study, in the open.
The library cites 363 studies across its deep-dives. This is all of them in one table — design, who was studied, for how long, what was reported, and the tier that row earned. 301 link straight to PubMed.
363Study rows indexed
264In human participants
234Randomised, crossover or pooled
301PMID-linked
Studied in
363study rows
- Human264
- Preclinical34
- Mixed6
- Not stated59
301 PMID-linked · 89/100 compounds
Open the index →Where the evidence was gathered · derived from the cited studies
Library · Evidence Tools
The Trial Index
Every study row cited by a compound deep-dive, gathered into one place. Nothing here is written for this page — each row is lifted from the table on the compound's own page, cell for cell, including the rows that report a null result or a harm.
Read this before the rows
Every cell is verbatim from the compound’s own deep-dive — design, sample size, duration and reported outcome are reproduced as written, and a column a source table never had shows an em-dash rather than being filled in from somewhere else. One thing on screen is derived: the small design class under each authored design, which is TNiC’s classification, not the study’s own label. It falls back to nothing rather than guessing, and a design naming both people and animals is counted as mixed, never as human evidence.
It is not complete, and the gap is stated rather than hidden: 89 of 100 compounds carry an evidence table, so 11 contribute no rows here. Of the rows that do, 264 describe human studies, 34 preclinical work, and 59 do not say — those are labelled not stated, not quietly counted as human. How the grading works
178
Randomised trial
71
Meta-analysis
15
Observational
34
Preclinical
All 363 cited study rows
Showing 363 of 363 study rows
| Study | Design | Studied in | Duration | Reported outcome | Tier |
|---|---|---|---|---|---|
| Kumar 2021 (PMID 33783984)GlyNAC (Glycine + NAC)PMID 33783984 | RCTRandomised trial | Humann=24 | 24 wk | ↑ GSH, ↓ oxidative stress, ↑ mitochondrial function | Tier A |
| Kumar 2023 (PMID 35975308)GlyNAC (Glycine + NAC)PMID 35975308 | RCT extensionRandomised trial | Humann=24 | 36 wk | Sustained GSH, improved insulin sensitivity | Tier A |
| Sekhar 2011GlyNAC (Glycine + NAC) | Pilot RCTRandomised trial | Humann=8 | 2 wk | ↑ GSH in elderly with oxidative stress | Tier B |
| Yi 2022 (36482258)NMN (Nicotinamide Mononucleotide) | RCT, dose-ranging (n=80)Randomised trial | Human | 60 d300 / 600 / 900 mg | ↑ NAD+ dose-dependently; peak effect at 600 mg | Tier A |
| Liao 2021 (34238308)NMN (Nicotinamide Mononucleotide) | RCT, amateur runners (n=48)Randomised trial | Human | 6 wk300 / 600 / 1200 mg | ↑ Aerobic capacity | Tier A |
| Yoshino 2021 (33888596)NMN (Nicotinamide Mononucleotide) | RCT, postmenopausal prediabetic womenRandomised trial | Human | 10 wk250 mg | ↑ Muscle insulin sensitivity | Tier A |
| Rajman 2018 (29514064)NMN (Nicotinamide Mononucleotide) | ReviewReview | Not stated | — | Therapeutic potential of NAD+-boosting molecules: the in vivo evidence | — |
| Martens 2018NR (Nicotinamide Riboside) | NR | Not stated | —1000 mg | ↑ whole-blood NAD+ | Tier A |
| Trammell 2016NR (Nicotinamide Riboside) | NR | Not stated | —100–1000 mg | ↑ NAD+ metabolites | Tier A |
| Yoshino 2021NR (Nicotinamide Riboside) | NMN | Not stated | —250 mg | ↑ Muscle insulin sensitivity | Tier A |
| Harrison 2009 (19587683)Rapamycin (Sirolimus) | Mice (heterogeneous)Preclinical | Preclinical | — | — | Preclinical → B |
| Bjedov 2010 (19587680)Rapamycin (Sirolimus) | MicePreclinical | Preclinical | — | — | Preclinical |
| Mannick 2014 (25540326)Rapamycin (Sirolimus) | Humans (elderly) | Human | — | — | Tier B |
| PEARL trialRapamycin (Sirolimus) | Humans | Human | — | — | Emerging |
| Dog Aging ProjectRapamycin (Sirolimus) | DogsPreclinical | Preclinical | — | — | Emerging |
| PreclinicalTUDCA (Tauroursodeoxycholic Acid) | Mouse neurodegenerationPreclinical | Preclinical | — | — | Tier C |
| PreclinicalTUDCA (Tauroursodeoxycholic Acid) | Cell culturePreclinical | Preclinical | — | — | Tier C |
| HumanTUDCA (Tauroursodeoxycholic Acid) | Cholestatic liver disease | Not stated | — | — | Tier B |
| Human longevityTUDCA (Tauroursodeoxycholic Acid) | — | Not stated | — | — | — |
| Zhang 2016 (PMID 27537554)Grape Seed Extract (95% OPC)PMID 27537554 | 16 RCTs, n=810Randomised trial | Human | — | ↓SBP (WMD −6.08 mmHg, P=0.011) | Tier B |
| Foshati 2022 (*Pharmacological Research* 175:105905)Grape Seed Extract (95% OPC) | 19 trials | Human | — | No significant SBP or FMD effect; ↓DBP and ↓heart rate significant | Tier B |
| Vigna et al. 2003 (*Metabolism* 52:1250–1257)Grape Seed Extract (95% OPC) | n=24, heavy smokers | Not stated | — | ↓TBARS 14.7% vs placebo (LDL oxidation marker) | Tier C(small trial) |
| Fahey / Dinkova-KostovaSulforaphane | MechanisticMechanistic | Not statedn=Cell + human tissue | Acute | KEAP1 modification, NRF2 nuclear translocation | Tier A |
| Riedl et al. airwaySulforaphane | Human ex vivoPreclinical | Mixedn=Epithelial | Hours | Dose-dependent ARE gene induction | Tier A |
| NRF2-NF-κB crosstalkSulforaphane | Review/mechanisticReview | Not stated | — | Inflammatory suppression downstream | Tier A |
| Ziegler 2011 (PMID 21309862)R-Alpha Lipoic Acid (R-ALA)PMID 21309862 | Meta-analysisMeta-analysis | Not statedDiabetic neuropathy | — | ↓ Neuropathy scores, ↓ oxidative stress | Tier B |
| Göçmen 2002R-Alpha Lipoic Acid (R-ALA) | RCTRandomised trial | HumanMetSyn | — | ↓ fasting glucose, ↓ TG | Tier B |
| Hagen 2002R-Alpha Lipoic Acid (R-ALA) | AnimalPreclinical | PreclinicalAged rat mito | — | ↑ mitochondrial activity, ↑ memory | — |
| Reed 2002R-Alpha Lipoic Acid (R-ALA) | MechanisticMechanistic | PreclinicalIn vitro/in vivo | — | Cofactor role for PDH, KGDH established | — |
| Shahmirzadi 2020 (PMID 32877690)Ca-AKG (Calcium Alpha-Ketoglutarate)PMID 32877690 | Controlled feeding | PreclinicalC57BL/6J mice | — | +12% median lifespan (F), ↓ frailty index | Tier A |
| [PMID 34847066] 2024Ca-AKG (Calcium Alpha-Ketoglutarate)PMID 34847066 | Open-label humanOpen-label / pilot | HumanMiddle-aged adults, 12 wk | — | ↑ AKG levels, ↓ inflammatory cytokines, ↓ clock age | Tier B |
| Gibson 2015Ca-AKG (Calcium Alpha-Ketoglutarate) | MechanisticMechanistic | PreclinicalIn vitro | — | TET cofactor role in epigenetic reprogramming | — |
| Su 2019Ca-AKG (Calcium Alpha-Ketoglutarate) | AnimalPreclinical | Preclinical*C. elegans* | — | AKG extends lifespan via AMPK/mTOR signaling | — |
| Baur 2006 (17086191)Trans-Resveratrol | MousePreclinical | Preclinical | Lifespan | Improved health on high-calorie diet | Preclinical |
| Yi 2022 (36482258)Trans-Resveratrol | Human RCTRandomised trial | Humann=300–900 mg | 60 d | NMN ↑ NAD+ (pair rationale) | Tier A(NMN leg) |
| Standalone human RCTsTrans-Resveratrol | Mixed | Not statedn=Varies | 4–12 wk | Inconsistent metabolic endpoints | Tier B/C |
| Singh 2023Taurine | Multi-species + human associationObservational | Mixed | — | Lifespan extension mice; taurine correlates with healthspan | Tier B |
| Animal lifespan studiesSpermidine | Yeast, nematode, fly, mousePreclinical | Preclinical | — | Consistent lifespan extension across four species; mouse cardioprotection and improved diastolic function among the most robust findings | Preclinical |
| Bruneck cohort (Kiechl 2018, PMID 29659968)SpermidinePMID 29659968 | Prospective cohortObservational | Human | — | Higher dietary spermidine intake associated with lower all-cause mortality | Tier B(observational) |
| Spermidine memory pilot (PMID 33932338)SpermidinePMID 33932338 | 3-month RCTRandomised trial | Human | — | Signal toward improved memory in older adults with subjective cognitive decline | Tier B |
| SmartAge (Schwarz 2022, PMID 35594044)SpermidinePMID 35594044 | 12-month RCTRandomised trial | Human | — | **Missed its primary memory endpoint** vs placebo | Tier B |
| Kapetanovic 2011Pterostilbene | Human PK/safetyPharmacokinetic | Human | — | 350 mg/day tolerated; higher exposure vs resveratrol | Tier B |
| PreclinicalPterostilbene | AnimalPreclinical | Preclinical | — | SIRT1/metabolic markers | Tier B/C |
| Yin 2008Berberine HCl | RCT vs metformin, T2D patientsRandomised trial | Human | — | ↓20% fasting glucose, ↓2.0 pts HbA1c | Tier A |
| Meta-analysis, 27 RCTs (PMID 26507383)Berberine HClPMID 26507383 | Mixed populations | Not stated | — | Consistent lipid + glucose improvement | Tier A |
| AMPK mechanism studies (PMID 17298901)Berberine HClPMID 17298901 | AnimalPreclinical | Preclinical | — | Confirmed Complex I inhibition → AMPK activation | Tier B(mechanistic) |
| Ryu 2019 (PMID 31230029)Urolithin APMID 31230029 | Human, middle-aged/older adults | Human | — | First evidence of stimulated mitophagy in skeletal muscle | Tier A |
| Phase 2 RCT (PMID 35391504)Urolithin APMID 35391504 | Human, adults ≥65 | Human | — | Improved gene expression, endurance, muscle strength vs placebo | Tier A |
| *C. elegans* lifespan study (PMID 27400265)Urolithin APMID 27400265 | AnimalPreclinical | Preclinical | — | Mitophagy induction, extended lifespan | Tier B(preclinical) |
| Kirkland lab, in vitro/mouse (PMID 30279143)FisetinPMID 30279143 | — | PreclinicalCell culture, mouse | — | Senescent cell clearance, extended healthspan/lifespan | Tier B(preclinical) |
| Mayo Clinic pilot RCT (PMID 30279143)FisetinPMID 30279143 | — | HumanHuman, older adults | — | ↓p16INK4A/p21, improved physical function | Tier B |
| Ongoing Phase 2 trialsFisetin | — | HumanHuman (NCT03675724, NCT04733534) | — | Results not yet published | — |
| Bioavailability trialsCoQ10 (Ubiquinol) | Ubiquinol vs ubiquinone | Not stated | — | Ubiquinol achieves ~3× higher plasma concentration | Tier A(PK data) |
| Jorat 2016 meta-analysis (17 RCTs)CoQ10 (Ubiquinol) | CoQ10 vs placebo | Not stated | — | ↓hs-CRP, ↓IL-6 | Tier A |
| Statin-depletion study (PMID 22395720)CoQ10 (Ubiquinol)PMID 22395720 | Statin users vs controls | Not stated | — | Documented muscle CoQ10 depletion on statins | Tier A |
| REDUCE-IT (PMID 30145934)Omega-3 (EPA + DHA)PMID 30145934 | — | HumanHigh-CV-risk adults, n=8,179 | — | ↓25% major adverse cardiovascular events | Tier A |
| SPM meta-analysis (PMID 32835509)Omega-3 (EPA + DHA)PMID 32835509 | — | Not statedMixed populations | — | ↓hs-CRP, ↓IL-6 via resolution mediators | Tier A |
| Telomere study (PMID 22245710)Omega-3 (EPA + DHA)PMID 22245710 | — | HumanHealthy older adults | — | Preserved leukocyte telomere length vs placebo | Tier A |
| Sesso 2022 — COSMOS (PMID: 35294962)Cocoa FlavanolsPMID 35294962 | RCTRandomised trial | Humann=21,442 | 3.6 y | Primary total-CVD **not** significant (HR 0.90, P=0.11); CVD death −27% (secondary) | Tier B |
| Baker 2022 — COSMOS-Mind (PMID: 36102337)Cocoa FlavanolsPMID 36102337 | RCTRandomised trial | Humann=2,262 | 3 y | **No** cognitive benefit from cocoa extract | — |
| Mollace 2019 (PMID: 30501605)Citrus BergamotPMID 30501605 | RCT (BPF / phytosome)Randomised trial | Humann=60 | — | Lower fasting glucose, LDL, TG; higher HDL in T2DM + hyperlipidemia | Tier B |
| Gliozzi 2013 (PMID: 24239156)Citrus BergamotPMID 24239156 | RCTRandomised trial | Humann=77 | 30 d | BPF 1000 mg lowered LDL-C and enhanced rosuvastatin's effect | Tier B |
| Cicero 2021 (PMID: 34345932)Citrus BergamotPMID 34345932 | Review / meta of lipid nutraceuticalsMeta-analysis | Not stated | — | Places BPF among effective, well-tolerated lipid-lowering nutraceuticals | Tier B |
| Owen 2008 (PMID: 18681988)L-TheaninePMID 18681988 | RCT, crossoverRandomised trial | Humann=27 | Acute | L-theanine + caffeine improved attention-switching, cut distractibility | Tier B |
| Giesbrecht 2010 (PMID: 21040626)L-TheaninePMID 21040626 | RCT, double-blindRandomised trial | Humann=44 | Acute | 97 mg theanine + 40 mg caffeine improved accuracy and alertness | Tier B |
| Kim 2018 (PMID: 29949889)Collagen PeptidesPMID 29949889 | RCT, double-blindRandomised trial | Humann=64 | 12 wk | 1,000 mg/d low-MW peptide improved hydration, elasticity, wrinkling | Tier B |
| Proksch 2013 (PMID: 23949208)Collagen PeptidesPMID 23949208 | RCT, double-blindRandomised trial | Humann=69 | 8 wk | 2.5–5 g/d improved skin elasticity vs placebo | Tier B |
| Bahadoran 2017 (PMID: 29141968)Beetroot / Dietary NitratePMID 29141968 | Meta-analysis (22 RCTs)Meta-analysis | Humann=~1,248 | 1–60 d | SBP −3.55 / DBP −1.32 mmHg; dose-dependent | Tier B |
| Ashor 2017 (PMID: 28319596)Beetroot / Dietary NitratePMID 28319596 | Meta-analysis (13 RCTs)Meta-analysis | Humann=325 | ≥1 wk | SBP −4.1 mmHg in clinic; **null on 24-h ambulatory** | Tier B |
| Lara 2015 (PMID: 25764393)Beetroot / Dietary NitratePMID 25764393 | Meta-analysis (12 RCTs)Meta-analysis | Humann=246 | 1.5 h–28 d | Endothelial function improved (SMD 0.36) | Tier B |
| Mori 2009 (PMID: 18844328)Lion's ManePMID 18844328 | RCT, double-blindRandomised trial | Humann=30 | 16 wk | Improved cognitive scores (HDS-R) at wk 8–16; **faded 4 wk after stopping** | Tier C |
| Saitsu 2019 (PMID: 31413233)Lion's ManePMID 31413233 | RCT, double-blindRandomised trial | Human | 12 wk | Improved MMSE vs placebo | Tier C |
| Nakazaki 2021 (PMID: 33978188)Citicoline (CDP-Choline)PMID 33978188 | RCT, double-blindRandomised trial | Humann=100 | 12 wk | 500 mg/d improved episodic & composite memory vs placebo in AAMI | Tier B |
| Brown 2012 (PMID: 22974472)Citicoline (CDP-Choline)PMID 22974472 | RCT, double-blindRandomised trial | Humann=60 | 12 wk | Antidepressant signal; better study retention (dual-diagnosis sample) | Tier C |
| Li 2023 (PMID: 39076715)NattokinasePMID 39076715 | Meta-analysis (6 RCTs)Meta-analysis | Humann=546 | — | SBP −3.45 / DBP −2.32 mmHg; lipid effects mixed; slight glucose rise | Tier B |
| Jensen 2016 (PMID: 27785095)NattokinasePMID 27785095 | RCT, double-blindRandomised trial | Humann=79 | 8 wk | 100 mg/d lowered BP and von Willebrand factor (N. American cohort) | Tier B |
| Rossman 2018 (PMID: 29661838)MitoQ (Mitoquinol)PMID 29661838 | RCT, crossoverRandomised trial | Humann=20 | 6 wk | Brachial FMD +42%; lower aortic stiffness & oxidized LDL in older adults | Tier B |
| Ried 2013 (PMID: 23169470)Aged Garlic ExtractPMID 23169470 | RCT, dose-responseRandomised trial | Humann=79 | 12 wk | Systolic BP −11.8 mmHg vs placebo (2-capsule/day) | Tier B |
| Ried 2010 (PMID: 20594781)Aged Garlic ExtractPMID 20594781 | RCTRandomised trial | Humann=50 | 12 wk | Systolic BP −10.2 mmHg in uncontrolled hypertension | Tier B |
| Ahmadi/Budoff 2010 (PMID: 20152239)Aged Garlic ExtractPMID 20152239 | RCT (AGE + supplement)Randomised trial | Humann=60 | 12 mo | Less coronary-artery-calcium progression, better vascular function | Tier B |
| Serrano 2023 (PMID: 37686723)Aged Garlic ExtractPMID 37686723 | RCT, triple-blindRandomised trial | Human | 12 wk | Smaller but significant BP drop with low-dose SAC black-garlic | Tier B |
| UKPDS 34 (PMID 9742977)MetforminPMID 9742977 | Humans, T2D (n=342) | Human | — | ↓ complications & all-cause mortality vs diet | Tier A(glycemic) |
| DPP, Knowler 2002 (PMID 11832527)MetforminPMID 11832527 | Humans, prediabetes | Human | — | ↓ diabetes incidence 31% (lifestyle 58%) | Tier A(prevention) |
| Barzilai 2016 (PMID 27304507)MetforminPMID 27304507 | Review / TAME rationaleReview | Not stated | — | Mechanistic + epidemiologic case; trial not reported | Tier B |
| Martin-Montalvo 2013 (PMID 23900241)MetforminPMID 23900241 | Male micePreclinical | Preclinical | — | 0.1% diet ↑ healthspan & lifespan; 1% dose toxic | Preclinical → B |
| NIA ITP, Strong 2016 (PMID 27312235)MetforminPMID 27312235 | Heterogeneous micePreclinical | Preclinical | — | Metformin **alone did not** extend lifespan; benefit only with rapamycin | Preclinical |
| Konopka 2019 (PMID 30548390)MetforminPMID 30548390 | Humans, older adults (RCT)Randomised trial | Human | — | Metformin **blunted** exercise-induced VO₂max, insulin-sensitivity & mitochondrial gains | Tier B(negative) |
| Chilibeck 2017 (PMID 29138605)Creatine MonohydratePMID 29138605 | Meta-analysis, 22 RCTsMeta-analysis | Humann=721 | 7–52 wk | +1.37 kg lean mass, ↑ upper/lower strength vs placebo + training | Tier A |
| Devries & Phillips 2014 (PMID 24576864)Creatine MonohydratePMID 24576864 | Meta-analysis of RCTsMeta-analysis | Human | ≥6 wk | ↑ muscle mass, strength, functional performance in older adults | Tier A |
| Kreider 2017 ISSN stand (PMID 28615996)Creatine MonohydratePMID 28615996 | Position stand / evidence reviewReview | Not stated | — | 3–5 g/day effective; up to 30 g/day for 5 yr shown safe | Tier A(performance) |
| Prokopidis 2023 (PMID 35984306)Creatine MonohydratePMID 35984306 | Meta-analysis, 8 RCTsMeta-analysis | Human | — | Memory SMD +0.29 overall; large in ages 66–76, null in young | Tier B |
| Xu 2024 (PMID 39070254)Creatine MonohydratePMID 39070254 | Meta-analysis, 16 RCTsMeta-analysis | Humann=492 | — | ↑ memory & processing speed; **no** effect on global/executive function | Tier B |
| Manson 2019 (PMID 30415629)Vitamin D3 (Cholecalciferol)PMID 30415629 | RCT, 2000 IU/dayRandomised trial | Humann=25,871 | 5.3 yr | No ↓ cancer (HR 0.96) or CV events (HR 0.97) | Tier A(null) |
| LeBoff 2022 (PMID 35939577)Vitamin D3 (Cholecalciferol)PMID 35939577 | RCT (VITAL ancillary), fracturesRandomised trial | Humann=25,871 | 5.3 yr | No ↓ total, nonvertebral, or hip fracture | Tier A(null) |
| Neale 2022 (PMID 35026158)Vitamin D3 (Cholecalciferol)PMID 35026158 | RCT, 60,000 IU/monthRandomised trial | Humann=21,315 | 5 yr | No ↓ all-cause mortality; exploratory ↑ cancer death | Tier A(null) |
| Hahn 2022 (PMID 35082139)Vitamin D3 (Cholecalciferol)PMID 35082139 | RCT (VITAL ancillary), autoimmuneRandomised trial | Humann=25,871 | 5.3 yr | ↓ incident autoimmune disease ~22% (HR 0.78) | Tier B |
| Keum 2019 (PMID 30796437)Vitamin D3 (Cholecalciferol)PMID 30796437 | Meta-analysis of RCTsMeta-analysis | Human | 3–10 yr | ↓ cancer *mortality* (RR 0.87) with daily dosing; no ↓ incidence | Tier B |
| Zhang 2016 (PMID 27402922)Magnesium (Glycinate / Threonate)PMID 27402922 | Meta-analysis, 34 RCTsMeta-analysis | Humann=2,028 | ~3 mo median | ↓SBP 2.00 / ↓DBP 1.78 mmHg | Tier B |
| Simental-Mendía 2016 (PMID 27329332)Magnesium (Glycinate / Threonate)PMID 27329332 | Meta-analysis of RCTsMeta-analysis | Humann=Multiple | Varied | ↓HOMA-IR overall; ↓fasting glucose only at ≥4 mo | Tier B |
| Mah & Pitre 2021 (PMID 33865376)Magnesium (Glycinate / Threonate)PMID 33865376 | Meta-analysis, 3 RCTsMeta-analysis | Humann=151 (older adults) | ≤12 wk | Sleep-onset latency ↓17.4 min; low-quality evidence | Tier C |
| Abbasi 2012 (PMID 23853635)Magnesium (Glycinate / Threonate)PMID 23853635 | Double-blind RCT, elderlyRandomised trial | Humann=46 | 8 wk | ↑Sleep time/efficiency, ↓ISI at 500 mg/day | Tier C |
| Liu 2016 / MMFS-01 (PMID 26519439)Magnesium (Glycinate / Threonate)PMID 26519439 | Double-blind RCT, L-threonateRandomised trial | Humann=44 | 12 wk | ↑Overall cognition vs placebo (d=0.91) | Tier C |
| Hu 2022 (PMID 35662923)Magnesium (Glycinate / Threonate)PMID 35662923 | Cross-sectional, NHANESObservational | Humann=4,039 | — | Higher dietary Mg ↔ longer leukocyte telomeres | Tier C(observational) |
| Kuptniratsaikul 2014 (PMID 24672232)Curcumin (Curcuminoids)PMID 24672232 | RCT vs ibuprofenRandomised trial | Humann=367 | 4 wk | Extract 1,500 mg/day ≈ ibuprofen on pain/WOMAC | Tier A(OA symptoms) |
| Feng 2022 meta-analysis (PMID 36261810)Curcumin (Curcuminoids)PMID 36261810 | Meta-analysis of RCTsMeta-analysis | Humann=multiple RCTs | ≤6 mo | Significant ↓VAS pain and ↓WOMAC vs control | Tier A(OA symptoms) |
| Wu 2025 meta-analysis (PMID 40615851)Curcumin (Curcuminoids)PMID 40615851 | Meta-analysis, 21 RCTsMeta-analysis | Humann=1,705 | varied | ↓CRP and ↓TNF-α; no significant change in ESR, IL-1β, IL-6, PGE2 | Tier B |
| Tabrizi 2019 meta-analysis (PMID 30402990)Curcumin (Curcuminoids)PMID 30402990 | Meta-analysis of RCTsMeta-analysis | Humann=multiple RCTs | varied | ↓hs-CRP, ↓IL-6, ↓MDA (oxidative stress) | Tier B |
| Zhu 2015 (PMID 25754370)QuercetinPMID 25754370 | Preclinical (cells + mice)Preclinical | Preclinical | — | First senolytics; D+Q cleared senescent cells, improved function, extended healthspan in mice | Tier B(mechanistic) |
| Hickson 2019 (PMID 31542391)QuercetinPMID 31542391 | Open-label pilot, diabetic kidney diseaseOpen-label / pilot | Not statedn=9 | — | 3-day D+Q reduced adipose senescent-cell burden (p16/p21, SA-β-gal) and some SASP markers within 11 days | Tier C(small, uncontrolled) |
| Justice 2019 (PMID 30616998)QuercetinPMID 30616998 | Open-label first-in-human pilot, IPFOpen-label / pilot | Humann=14 | — | Intermittent D+Q (Q 1250 mg/day) improved 6-min walk, gait speed, chair-stands; lung function unchanged | Tier C(small, uncontrolled) |
| Nambiar 2023 (PMID 36857968)QuercetinPMID 36857968 | Phase I RCT (placebo-controlled), IPFRandomised trial | Humann=12 | — | D+Q feasible and generally well-tolerated; not powered for efficacy | Tier B(Phase I) |
| Serban 2016 (PMID 27405810)QuercetinPMID 27405810 | Meta-analysis, 7 RCTsMeta-analysis | Humann=587 | — | ↓SBP ~3.0 mmHg, ↓DBP ~2.6 mmHg; effect concentrated at >500 mg/day | Tier B |
| Ma 2019 (PMID 31088786)Glucosamine SulfatePMID 31088786 | Prospective cohortObservational | Humann=466,039 | — | ↓ total CVD (HR 0.85), ↓ CVD death (HR 0.78) | Tier B(observational) |
| Li 2020 (PMID 32253185)Glucosamine SulfatePMID 32253185 | Prospective cohortObservational | Humann=495,077 | — | ↓ all-cause (HR 0.85), ↓ CVD (HR 0.82) mortality | Tier B(observational) |
| Weimer 2014 (PMID 24714520)Glucosamine SulfatePMID 24714520 | Nematode + mousePreclinical | Preclinical | — | +5% (worm), +10% (mouse) lifespan | Tier C(preclinical) |
| Clegg/GAIT 2006 (PMID 16495392)Glucosamine SulfatePMID 16495392 | RCT, glucosamine HClRandomised trial | Humann=1,583 | — | No significant pain benefit overall vs placebo | Tier A(for OA, null) |
| Simental-Mendía 2018 (PMID 29947998)Glucosamine SulfatePMID 29947998 | Meta-analysis of RCTsMeta-analysis | Human | — | Modest pain/function benefit for the sulfate form | Tier B(for OA) |
| Knapen 2015 (PMID 25694037)Vitamin K2 (MK-7)PMID 25694037 | RCT, 180 µg/day MK-7Randomised trial | Humann=244 | 3 yr | ↑ carotid distensibility, ↓ inactive MGP | Tier B |
| Knapen 2013 (PMID 23525894)Vitamin K2 (MK-7)PMID 23525894 | RCT, 180 µg/day MK-7Randomised trial | Humann=244 | 3 yr | Slowed BMD decline at spine + femoral neck; ↓ uncarboxylated osteocalcin | Tier B |
| Rønn 2021 (PMID 33030563)Vitamin K2 (MK-7)PMID 33030563 | RCT, 375 µg/day MK-7Randomised trial | Humann=142 | 3 yr | Osteocalcin carboxylation ↑ but **no BMD difference** vs placebo in osteopenic women | Tier B |
| Ma 2022 meta-analysis (PMID 36033779)Vitamin K2 (MK-7)PMID 36033779 | 16 RCTsRandomised trial | Humann=6,425 | Mixed | Significant ↑ lumbar-spine BMD (P=0.006), but pooled MK-4 + MK-7 trials of varying quality | Tier B |
| Geleijnse 2004 (PMID 15514282)Vitamin K2 (MK-7)PMID 15514282 | Prospective cohort (Rotterdam)Observational | Humann=4,807 | ~7–10 yr | Higher dietary menaquinone linked to ↓ CHD mortality + severe aortic calcification | Tier C(observational) |
| Ferracioli-Oda 2013 (PMID 23691095)MelatoninPMID 23691095 | Meta-analysis, 19 RCTsMeta-analysis | Humann=1683 | — | ↓Sleep latency −7.06 min; ↑total sleep time | Tier A |
| Buscemi 2005 (PMID 16423108)MelatoninPMID 16423108 | Meta-analysis, primary sleep disordersMeta-analysis | Not stated | — | ↓Latency (large in DSPS, modest in insomnia) | Tier A |
| Dose-response MA 2024 (PMID 38888087)MelatoninPMID 38888087 | Meta-analysis, 26 RCTsMeta-analysis | Humann=1689 obs | — | Latency benefit peaks ~4 mg/day | Tier A |
| Akbari 2018 (PMID 29907916)MelatoninPMID 29907916 | Meta-analysis, 6 RCTsMeta-analysis | Humann=317 | — | ↓CRP and ↓IL-6; no TNF-α effect | Tier B |
| Lauritzen 2021 (PMID 34370338)MelatoninPMID 34370338 | Meta-analysisMeta-analysis | Not stated | — | Slight ↓fasting insulin; no fasting-glucose change | Tier B |
| Reiter 2002 (PMID 11976199)MelatoninPMID 11976199 | Mechanistic reviewReview | Not stated | — | ↑Mitochondrial respiration; aging effect unproven | Tier C |
| Díaz-Flores 2013 (PMID 24144057)GlycinePMID 24144057 | RCT, metabolic syndromeRandomised trial | Humann=60 | 3 months | ↓ TBARS ~25%, ↓ systolic BP in men | Tier B |
| Bannai 2012 (PMID 22529837)GlycinePMID 22529837 | Crossover, sleep-restrictedCrossover | Humann=10 | Acute | ↓ fatigue/sleepiness, better vigilance next day | Tier B |
| Kumar 2023 — GlyNAC (PMID 35975308)GlycinePMID 35975308 | RCT, older adultsRandomised trial | Humann=24 | 16 wk | ↑ glutathione, ↓ oxidative stress, ↑ mitochondrial function (glycine **+** NAC) | Tier A(for the combination) |
| Miller 2019 — NIA ITP (PMID 30916479)GlycinePMID 30916479 | Mouse lifespanPreclinical | Preclinicaln=~1000+ | Lifelong | 8% glycine diet → +4–6% median lifespan, both sexes | Tier C(preclinical) |
| Kumar 2023 (PMID 35975308)N-Acetylcysteine (NAC)PMID 35975308 | RCT, GlyNAC vs placebo, older adultsRandomised trial | Humann=24 older + 12 young | 16 wk | ↑GSH, ↓oxidative stress/inflammation, ↑gait speed & strength | Tier B(combination) |
| Kumar/Sekhar 2022 (PMID 35821844)N-Acetylcysteine (NAC)PMID 35821844 | RCT, GlyNAC dosing, older adultsRandomised trial | Human | 16 wk | ↑GSH mainly in high-stress/low-GSH subgroup | Tier B(combination) |
| Flurkey 2010 (PMID 20819793)N-Acetylcysteine (NAC)PMID 20819793 | Mouse lifespan (NIA-style)Preclinical | Preclinicaln=Genetically heterogeneous mice | Lifelong | ↑Male median lifespan, but confounded by reduced food/water intake | Tier C(animal, confounded) |
| Berk 2014 (PMID 25004186)N-Acetylcysteine (NAC)PMID 25004186 | RCT, adjunctive NAC in MDDRandomised trial | Humann=252 | 12–16 wk | No week-12 separation; some benefit in severe subgroup | Tier B(mixed) |
| Fernandes/updated meta-analysis 2024 (PMID 39504621)N-Acetylcysteine (NAC)PMID 39504621 | Meta-analysis, 12 RCTsMeta-analysis | Humann=904 | 8–24 wk | Small but significant depression-score reduction; strongest in bipolar | Tier B(modest) |
| Prasad 2007 (PMID 17344507)ZincPMID 17344507 | RCT, adults 55–87Randomised trial | Humann=50 | 12 months | ↓ infection incidence; ↓ TNF-α; ↓ oxidative-stress markers | Tier B |
| Science 2012 meta-analysis (PMID 22566526)ZincPMID 22566526 | Meta-analysis, 17 RCTsMeta-analysis | Humann=2121 | Acute (colds) | Adults ~2.6 days shorter cold duration; no benefit in children; high heterogeneity (I²≈95%) | Tier B |
| Haase & Rink 2009 (PMID 19523191)ZincPMID 19523191 | Mechanistic reviewReview | Not stated | — | Maps zinc-deficiency immune changes onto immunosenescence | Tier B(mechanistic) |
| Mocchegiani 2013 (PMID 22222917)ZincPMID 22222917 | ReviewReview | Not stated | — | Elderly often below RDA; supplementation supports immune function; response varies by IL-6 genotype | Tier B(review) |
| Bettuzzi 2006 (PMID 16424063)EGCG (Green Tea Catechin)PMID 16424063 | RCT, HG-PIN patientsRandomised trial | Humann=60 | — | 600 mg/day GTC: 3% vs 30% one-year prostate cancer incidence | Tier B(single small trial, unreplicated) |
| Khalesi 2014 (PMID 24861099, *Eur J Nutr*)EGCG (Green Tea Catechin)PMID 24861099 | Meta-analysis, 13 RCTsMeta-analysis | Human | — | Green tea catechins: SBP −2.08 mmHg, DBP −1.71 mmHg vs control | Tier B |
| Xu 2020 (PMID 32434539, *Nutrition Journal*)EGCG (Green Tea Catechin)PMID 32434539 | Meta-analysis, 31 RCTsMeta-analysis | Humann=3,321 | — | ↓Total cholesterol and ↓LDL; no significant effect on HDL or triglycerides | Tier B |
| Hursel 2009 (PMID 19597519, *Int J Obesity*)EGCG (Green Tea Catechin)PMID 19597519 | Meta-analysis, weight-loss trialsMeta-analysis | Human | — | Catechin-caffeine mixtures: modest but significant body-weight reduction/maintenance | Tier C(small, caffeine-confounded effect) |
| Zhou 2021 meta-analysis (PMID 34578794)AstaxanthinPMID 34578794 | Meta-analysis, 11 controlled studiesMeta-analysis | Not statedn=pooled | ≤12 wk | ↑elasticity (SMD 0.77), ↑moisture, ↓wrinkles | Tier B |
| Ito 2018 (PMID 29941810)AstaxanthinPMID 29941810 | RCT vs placebo, 4 mg/dayRandomised trial | Humann=23 | 10 wk | ↑UV tolerance (MED), ↓UV-induced TEWL, ↑texture | Tier B |
| Park 2010 (PMID 20205737)AstaxanthinPMID 20205737 | RCT vs placebo, 2 or 8 mg/dayRandomised trial | Humann=young healthy women | 8 wk | ↓DNA-oxidation marker, ↓acute-phase protein, ↑immune response | Tier B |
| Liu 2021 (PMID 34110707)AstaxanthinPMID 34110707 | RCT, 12 mg/day astaxanthin (co-formulated with tocotrienol + zinc) + aerobic training vs training aloneRandomised trial | Humann=42, age 65–82 | 3 mo | ↑fat oxidation, improved exercise efficiency in older males | Tier C(confounded by co-ingredients) |
| 2025 cycling RCT (PMID 40615903, *BMC Sports Sci Med Rehabil* 17:180)AstaxanthinPMID 40615903 | RCT, 28 mg/day, short-term loadingRandomised trial | Humann=10, young male cyclists | 4 days | ↑time-to-exhaustion, blunted CK/LDH rise, blunted MDA rise | Tier C(very small n) |
| Escande 2013 (PMID 23172919)ApigeninPMID 23172919 | Mouse (diet-induced obesity) + in vitroPreclinical | Preclinical | — | ↑ hepatic NAD+, ↑ SIRT1/SIRT3 activity, improved glucose/lipid handling | Tier C(preclinical) |
| Lauritzen 2024 (PMID 39840045, *Front Immunol*)ApigeninPMID 39840045 | Human monocyte/macrophage culturePreclinical | Mixed | — | Apigenin blocked NLRP3-driven IL-1β release, independent of CD38 | Tier C(mechanistic, human cells) |
| Perrott 2017 (PMID 28378188, *GeroScience*)ApigeninPMID 28378188 | Human fibroblast culture, 3 senescence modelsPreclinical | Mixed | — | Suppressed SASP cytokines (esp. CXCL10) via IL-1α/NF-κB pathway | Tier C(mechanistic) |
| Gradolatto 2006 (PMID 16407641, *Ann Nutr Metab*)ApigeninPMID 16407641 | Human PK, n=11, single dosePharmacokinetic | Human | — | Apigenin poorly absorbed from food; plasma Cmax ~127 nmol/L at 7.2h | Tier B(PK only) |
| Amsterdam 2009 (PMID 19593179, *J Clin Psychopharmacol*)ApigeninPMID 19593179 | RCT, n=57, GAD patients, 8 wkRandomised trial | Human | — | Chamomile extract significantly reduced anxiety (HAM-A) vs placebo (P=0.047) | Tier B(chamomile extract, not isolated apigenin) |
| Zick 2011 (PMID 21939549, *BMC Complement Altern Med*)ApigeninPMID 21939549 | RCT, n=34, chronic insomnia, 28 daysRandomised trial | Human | — | No significant improvement in sleep-diary measures vs placebo | Tier B(null result, chamomile extract) |
| Smith 2020 (PMID 31672783)ErgothioneinePMID 31672783 | Prospective cohort (Malmö Diet & Cancer)Observational | Humann=3,236 | 21.4 yr median follow-up | ↓CHD, ↓CV mortality, ↓all-cause mortality per SD plasma ERGO | Tier B(observational, non-causal) |
| Katsube 2024 (PMID 38446314, *GeroScience*)ErgothioneinePMID 38446314 | Lifespan study, male mice, dietary ERGO ~4–5 mg/kg/dayPreclinical | Preclinicaln=cohort study | Lifetime | +16% median lifespan; +29% 90th-percentile survival age; less age-related fat/weight loss | Tier C(animal) |
| Tian 2021 "ErgMS" (PMID 34715934, *Pilot and Feasibility Studies*)ErgothioneinePMID 34715934 | RCT protocol, metabolic syndrome, 3-arm (placebo / 5 mg / 30 mg/day)Randomised trial | Humann=pilot-scale | 12 wk | Protocol publication only — as of this review, outcome data have not been published | Pending |
| Cheah et al. 2025 (*Nutraceuticals* 5(3):15; not yet PubMed-indexed)Ergothioneine | RCT, older adults with subjective memory complaints, 10 mg vs 25 mg vs placeboRandomised trial | Humann=147 | 16 wk | Plasma ERGO rose 6–16× at 25 mg; some within-group cognitive-domain gains and a 25 mg dose-dependent improvement in prospective memory/sleep-onset, but primary composite memory gain at 25 mg was not sustained between groups | Tier C(preliminary) |
| de Courten 2016 (PMID 27040154, *Obesity*)L-CarnosinePMID 27040154 | Pilot RCTRandomised trial | Humann=non-diabetic, some with impaired glucose tolerance | 12 wk | Improved glucose handling in the impaired-glucose-tolerance subgroup (P<0.05) | Tier C(pilot) |
| de Courten 2024 (PMID 38172006, *Nutr Metab Cardiovasc Dis*)L-CarnosinePMID 38172006 | RCT, 2 g/dayRandomised trial | Humann=43 | 14 wk | ↓ OGTT glucose at 90/120 min, ↓ glucose AUC vs placebo | Tier B(single trial) |
| Houjeghani 2018 (PMID 29420997, *Nutrition Research*)L-CarnosinePMID 29420997 | Double-blind RCT, 1,000 mg/dayRandomised trial | Humann=54 (T2D) | 12 wk | ↓ fasting glucose (−13.1 mg/dL), ↓ HbA1c (−0.6%), ↓ triglycerides, ↓ TNF-α, ↓ AGEs | Tier B |
| Meta-analysis (PMID 31987255, *Complement Ther Med*)L-CarnosinePMID 31987255 | Systematic review of long-term RCTsMeta-analysis | Humann=multiple RCTs | varied | ↓ HbA1c; **no significant effect** on fasting glucose, lipids, or insulin resistance | Tier B(mixed) |
| Chez 2002 (PMID 12585724, *Journal of Child Neurology*)L-CarnosinePMID 12585724 | Double-blind RCT, 800 mg/dayRandomised trial | Humann=31 children with ASD | 8 wk | ↑ GARS total score and Behavior/Socialization/Communication subscales vs placebo | Tier C(single small trial, not consistently replicated) |
| Krokowicz 2014 (PMID 24343275)Butyrate (Sodium / Tributyrin)PMID 24343275 | RCT, diverticulosisRandomised trial | Humann=52 completers | 12 months | ↓diverticulitis episodes: 6.7% vs 31.8% controls (p=0.043) | Tier B |
| Banasiewicz 2013 (PMID 22738315)Butyrate (Sodium / Tributyrin)PMID 22738315 | RCT, IBS (adjunct therapy)Randomised trial | Humann=66 | 12 wk | ↓pain on defecation, improved urgency/bowel habit; overall pain-severity change not significant | Tier B |
| Firoozi 2024 (PMID 39003477)Butyrate (Sodium / Tributyrin)PMID 39003477 | Double-blind RCT, active ulcerative colitisRandomised trial | Humann=36 | 12 wk | ↓inflammatory markers, upregulated circadian-clock genes, improved sleep quality and QoL | Tier B |
| Panufnik 2026 (PMID 41974937)Butyrate (Sodium / Tributyrin)PMID 41974937 | RCT, type 2 diabetes with GI symptomsRandomised trial | Humann=52 | 12 wk | ↓abdominal pain/diarrhea/bloating; ↓HbA1c and HOMA-IR vs placebo | Tier B |
| Mitrović 2025 (PMID 40565024)Butyrate (Sodium / Tributyrin)PMID 40565024 | RCT, MASLDRandomised trial | Humann=181 | interventional trial | **No significant change** in primary liver-fat endpoint (CAP); selective subgroup metabolic improvements only | Tier C(null primary) |
| Sato 2020 (PMID 32882837)Butyrate (Sodium / Tributyrin)PMID 32882837 | Animal mechanism, diet-induced obese micePreclinical | Preclinical | 6 wk | Tributyrin ↓weight gain, ↑insulin sensitivity via GPR109A-dependent adipose remodeling | Tier C(preclinical) |
| Chandrasekhar 2012 (PMID 23439798)Ashwagandha (Withania somnifera)PMID 23439798 | RCT vs placeboRandomised trial | Humann=64 | 60 days | ↓Stress-scale scores (P<0.0001); ~28% ↓serum cortisol | Tier B |
| Akhgarjand 2022 meta-analysis (PMID 36017529)Ashwagandha (Withania somnifera)PMID 36017529 | Meta-analysis, 12 RCTsMeta-analysis | Humann=1,002 | ≤12 wk | Pooled ↓anxiety (SMD −1.55), ↓stress (SMD −1.75); high heterogeneity | Tier B |
| Langade 2020 (PMID 32540634)Ashwagandha (Withania somnifera)PMID 32540634 | RCT vs placebo, healthy adultsRandomised trial | Humann=150 | 6 wk | 120 mg/day (Shoden) → 72% self-reported sleep-quality improvement vs 29% placebo | Tier B |
| Wankhede 2015 (PMID 26609282)Ashwagandha (Withania somnifera)PMID 26609282 | RCT vs placebo, resistance-trained menRandomised trial | Humann=57 | 8 wk | 300 mg BID → greater bench-press/leg-extension strength, muscle size, and testosterone gains vs placebo | Tier B |
| Björnsson 2020 (PMID 31991029)Ashwagandha (Withania somnifera)PMID 31991029 | Case series, DILIN + IcelandObservational | Humann=5 | — | Cholestatic/mixed liver injury; 4/5 normalized in 1–5 months, none fatal in this series | Safety signal |
| Rizza 2011 (PMID 21346065)HesperidinPMID 21346065 | RCT, crossover, placebo-controlledRandomised trial | Humann=24, metabolic syndrome | 3 wk | ↑FMD, ↓inflammatory/adhesion markers, in-vitro eNOS activation confirmed | Tier B |
| Morand 2011 (PMID 21068346)HesperidinPMID 21068346 | RCT, crossoverRandomised trial | Humann=24, healthy overweight men 50–65y | 4 wk chronic + acute arm | ↓diastolic BP (chronic); ↑postprandial microvascular reactivity (acute) | Tier B |
| Valls 2021 / CITRUS (PMID 32661681)HesperidinPMID 32661681 | RCT, parallel, double-blind, placebo-controlledRandomised trial | Humann=159, elevated BP / stage-1 hypertension | 12 wk | ↓SBP and pulse pressure, dose-dependent with hesperidin content | Tier B |
| Salden 2016 (PMID 27797708)HesperidinPMID 27797708 | RCT, double-blind, placebo-controlledRandomised trial | Humann=68, overweight/obese | 6 wk | No FMD change in full population; subgroup (baseline FMD ≥3%) showed improved postprandial endothelial function | Tier C(null primary endpoint) |
| Mohammadi 2019 meta-analysis (PMID 30632207)HesperidinPMID 30632207 | Meta-analysis, 10 RCTsMeta-analysis | Humann=577 pooled | ≤12 wk trials | No significant pooled effect on TC, LDL, HDL, TG, SBP, or DBP | Tier B(contradicts positive trials) |
| Sengupta 2008 (PMID 18667054)Boswellia serrata (AKBA)PMID 18667054 | RCT vs placebo, 5-Loxin 100/250 mgRandomised trial | Humann=75 | 90 d | ↓pain/function both doses; effect by day 7 at 250 mg | Tier B |
| Sengupta 2010 (PMID 21060724)Boswellia serrata (AKBA)PMID 21060724 | RCT, 5-Loxin vs Aflapin vs placebo, 100 mg eachRandomised trial | Humann=60 | 90 d | Both extracts beat placebo; Aflapin outperformed 5-Loxin | Tier B |
| Yu 2020 meta-analysis (PMID 32680575)Boswellia serrata (AKBA)PMID 32680575 | Meta-analysis, 7 RCTsMeta-analysis | Humann=545 | ≤90 d | Significant ↓VAS, ↓WOMAC pain/stiffness/function | Tier B |
| Nischang 2025 (PMID 41075523)Boswellia serrata (AKBA)PMID 41075523 | Mechanistic, human macrophagesMechanistic | Human | — | Low-AKBA extract beat high-AKBA extract on lipid mediator class switch | Tier C(mechanistic) |
| Park 2014 (PMID 23804546)Gynostemma pentaphyllum (Jiaogulan)PMID 23804546 | RCT vs. placebo, obese adultsRandomised trial | Humann=80 | 12 wk | ↓abdominal fat area, ↓body weight, ↓BMI at 450 mg/day | Tier B(single trial) |
| Rao 2022 (PMID 34323337)Gynostemma pentaphyllum (Jiaogulan)PMID 34323337 | RCT vs. placebo, overweight adultsRandomised trial | Humann=117 | 16 wk | ↓total fat mass, ↓BMI, ↓gynoid fat; ↓triglycerides, ↓TNF-α at 450 mg/day | Tier B(single trial) |
| Nayyar 2023 (PMID 38004115)Gynostemma pentaphyllum (Jiaogulan)PMID 38004115 | RCT crossover, healthy untrained malesRandomised trial | Humann=16 | 4 wk + washout | ↑20 km time-trial performance, ↑muscle AMPK-Thr172 phosphorylation post-exercise, ↓fasting glucose & leptin | Tier B(mechanistic + performance) |
| Xie 2022 systematic review (PMID 36091752)Gynostemma pentaphyllum (Jiaogulan)PMID 36091752 | Systematic review, 22 RCTsMeta-analysis | Humann=2,407 | Varied | Comparable to n-3 fatty acids / red yeast rice on triglycerides, total cholesterol, HDL; fewer adverse events than statins/fibrates | Tier C(heterogeneous trial quality) |
| Yang 2012 (PMID 22576281)Gynostemma pentaphyllum (Jiaogulan)PMID 22576281 | Preclinical — L6 myotubes + ob/ob micePreclinical | Preclinicaln=Cell/animal | 8 wk (in vivo arm) | Identified damulins A/B as the AMPK-active fraction; ↓body weight gain, ↓liver weight, ↓cholesterol in mice | Tier C(mechanistic/animal) |
| Hsu 2021 (PMID 34203487)Hyaluronic Acid (Oral)PMID 34203487 | RCT, placebo-controlledRandomised trial | Humann=40 | 120 mg/day, 12 wk | ↑hydration (p=0.0003), ↓TEWL (p=0.009), ↓wrinkle volume (p=0.048) | Tier B |
| Dolečková 2025 (PMID 41422283)Hyaluronic Acid (Oral)PMID 41422283 | RCT, dose-ranging (60 vs 120 mg)Randomised trial | Humann=150 | 60/120 mg/day, 12 wk | Dose-dependent: SH120 ↑hydration ~11.5%, ↓TEWL, ↓periorbital wrinkle depth vs placebo | Tier B |
| Zhang 2023 (PMID 38009035)Hyaluronic Acid (Oral)PMID 38009035 | RCT, dose-ranging (100 vs 200 mg)Randomised trial | Humann=129 | 100/200 mg/day, 12 wk | ↑hydration from week 2–8; ↑epidermal thickness at 12 wk; stable dermal density vs placebo decline | Tier B |
| Amin 2025 meta-analysis (PMID 40911749)Hyaluronic Acid (Oral)PMID 40911749 | Meta-analysis, 7 RCTsMeta-analysis | Humann=pooled | varied | Significant ↑hydration, ↑elasticity, ↓wrinkle depth; firmness/TEWL pooled effects not significant | Tier B |
| Concia/FS-HA trial 2020 (PMID 32650511)Hyaluronic Acid (Oral)PMID 32650511 | RCT, placebo-controlled, knee OARandomised trial | Humann=60 | 200 mg/day, 56 d | ↓VAS pain, ↓WOMAC total vs baseline and vs placebo (p<0.05); reduced NSAID use | Tier B |
| Balogh 2008 (PMID 18959406)Hyaluronic Acid (Oral)PMID 18959406 | Tracer/mechanistic, rats & dogsPreclinical | Preclinicaln=animal | single dose | Radiolabeled oral HA taken up systemically, concentrated in joints/vertebrae within 15 min | Tier C(mechanistic, animal) |
| Wang 2019 (PMID 31805963)Inulin / Prebiotic FiberPMID 31805963 | Meta-analysis, 33 RCTsMeta-analysis | Humann=1,346 | ≤6 wk best at ≥10 g/day | ↓FBG −0.60 mmol/L, ↓HbA1c −0.58% (high-quality); ↓insulin, ↓HOMA-IR (low-quality) | Tier B |
| Le Bastard 2020 (PMID 31707507)Inulin / Prebiotic FiberPMID 31707507 | Systematic review, 9 studies (7 RCTs)Meta-analysis | Humann=varied | varied | Most consistent finding: ↑*Bifidobacterium*; SCFA/other taxa changes inconsistent | Tier B |
| Boets 2015 (PMID 26516911)Inulin / Prebiotic FiberPMID 26516911 | Stable-isotope mechanistic studyMechanistic | Not statedn=12 | Single 15 g dose | Direct quantification: ~137 mmol acetate, ~20 mmol butyrate, ~11 mmol propionate produced over 12 h | Tier B(mechanistic) |
| Chambers 2019 (PMID 30971437, *Gut*)Inulin / Prebiotic FiberPMID 30971437 | RCT, crossover vs celluloseRandomised trial | Humann=12 | 42-day periods | Inulin improved insulin sensitivity vs cellulose; unlike its propionate-ester derivative, plain inulin did **not** reduce IL-8 or other inflammatory markers | Tier B |
| Birkeland 2021 (PMID 34589204, *J Nutr Sci*)Inulin / Prebiotic FiberPMID 34589204 | RCT, crossover, T2D patientsRandomised trial | Humann=29 | 6 wk | No effect on ghrelin, hunger, fullness, or energy intake; PYY rose *less* after inulin than after control | Tier B(null result) |
| Micka 2017 (PMID 27492975, *Int J Food Sci Nutr*)Inulin / Prebiotic FiberPMID 27492975 | RCT, crossover, constipated adultsRandomised trial | Humann=44 | 4 wk | Stool frequency ↑ to 4.0 vs 3.0 stools/week on placebo (p=0.038), softer stools | Tier B |
| Lippman 2009 (SELECT), PMID 19066370SeleniumPMID 19066370 | RCT, 200 µg/d selenomethionineRandomised trial | Humann=35,533 | — | No prostate/overall cancer benefit; stopped for futility | Tier A(null) |
| Stranges 2007, PMID 17620655SeleniumPMID 17620655 | RCT (NPC secondary analysis), 200 µg/dRandomised trial | Humann=1,202 | — | ↑ type 2 diabetes incidence, HR 1.55 (95% CI 1.03–2.33) | Tier B |
| Vinceti 2018 meta-analysis, PMID 29974401SeleniumPMID 29974401 | Systematic review/meta-analysisMeta-analysis | Not statedn=Multiple | — | Selenium "may increase the risk of type 2 diabetes" across exposure levels | Tier B |
| Kong 2024 meta-analysis, PMID 38243784SeleniumPMID 38243784 | Meta-analysis of RCTs, Hashimoto'sMeta-analysis | Humann=Multiple RCTs | — | ↓ TSH and ↓ thyroid antibodies (TPOAb) with selenium | Tier B |
| Chowanadisai 2010 (PMID 19861415)PQQ (Pyrroloquinoline Quinone)PMID 19861415 | In vitro / mouse cellsPreclinical | Preclinical | — | CREB→PGC-1α→↑mtDNA, respiration | Tier C(preclinical) |
| Harris 2013 (PMID 24231099)PQQ (Pyrroloquinoline Quinone)PMID 24231099 | Human crossoverCrossover | Humann=10 | — | ↓CRP, ↓IL-6; shifted mito metabolites | Tier C(small pilot) |
| Itoh 2016, BioPQQ (PMID 26782228)PQQ (Pyrroloquinoline Quinone)PMID 26782228 | RCT, elderlyRandomised trial | Humann=41 | — | ↑ selected attention/visuospatial scores | Tier C(small, sponsored) |
| Tamakoshi 2023 (PMID 36807425)PQQ (Pyrroloquinoline Quinone)PMID 36807425 | RCT, adults 20–65Randomised trial | Humann=~66 | — | Age-stratified memory/processing gains | Tier C(small) |
| Dihydro-PQQ mixture 2024 (PMID 38908296)PQQ (Pyrroloquinoline Quinone)PMID 38908296 | RCT, MCI elderlyRandomised trial | Humann=34 | — | ↑BDNF, ↑brain NAA; MMSE n.s. between groups | Tier C(small, combination product) |
| De Jesus Moreno 2003 (PMID 12637119)Alpha-GPC (L-Alpha-Glycerylphosphorylcholine)PMID 12637119 | RCTRandomised trial | Humann=261 | 180 d | ↑ MMSE, ↑ ADAS-Cog in mild–moderate AD | Tier B |
| Amenta ASCOMALVA 2014 (PMID 24525715)Alpha-GPC (L-Alpha-Glycerylphosphorylcholine)PMID 24525715 | RCTRandomised trial | Humann=210 | 12 mo | Adjunct to donepezil beats donepezil alone | Tier B |
| Kawamura 2012 (PMID 22673596)Alpha-GPC (L-Alpha-Glycerylphosphorylcholine)PMID 22673596 | Acute RCTRandomised trial | Humann=8 | Single dose | ~500% GH surge 60 min post-dose | Tier C |
| Ziegenfuss 2008 (PMID 18834505)Alpha-GPC (L-Alpha-Glycerylphosphorylcholine)PMID 18834505 | CrossoverCrossover | Humann=13 | 6 d | ↑ Isometric mid-thigh pull force in trained males | Tier C |
| Crook 1991 (PMID 1876787)Phosphatidylserine (PS)PMID 1876787 | RCT (bovine PS)Randomised trial | Humann=149 | 12 wk | ↑ memory, learning in age-associated impairment | Tier B |
| Starks 2008 (PMID 18662395)Phosphatidylserine (PS)PMID 18662395 | CrossoverCrossover | Humann=10 | 10 d | ↓ Post-exercise cortisol; ↑ testosterone:cortisol ratio | Tier B |
| Hellhammer 2004 (PMID 15512856)Phosphatidylserine (PS)PMID 15512856 | RCTRandomised trial | Humann=60 | 42 d | ↓ ACTH, ↓ cortisol response to mental stress | Tier B |
| Vakhapova 2010 (PMID 20130432)Phosphatidylserine (PS)PMID 20130432 | RCT (soy PS + DHA)Randomised trial | Humann=157 | 15 wk | Modest verbal recall gains in age-related complaint | Tier C |
| Le Bars 1997 (PMID 9343463)Ginkgo Biloba (EGb 761)PMID 9343463 | RCT (EGb 761)Randomised trial | Humann=309 | 52 wk | ↑ ADAS-Cog 1.4 in AD/MID | Tier B |
| Ihl 2011 meta (PMID 21129580)Ginkgo Biloba (EGb 761)PMID 21129580 | Meta-analysisMeta-analysis | Not statedn=2561 | 12–26 wk | ↑ Cognition, behavioral symptoms at 240 mg | Tier B |
| GEM 2008 (PMID 19017911)Ginkgo Biloba (EGb 761)PMID 19017911 | RCT (prevention)Randomised trial | Humann=3069 | 6+ yr | **No prevention** of dementia in healthy elderly | Tier A(neg) |
| Amieva 2013 (PMID 24086148)Ginkgo Biloba (EGb 761)PMID 24086148 | RCTRandomised trial | Humann=2854 | 5 yr | **No slowing** of cognitive decline in memory-complaint elderly | Tier B |
| Herrschaft 2012 (PMID 22591951)Ginkgo Biloba (EGb 761)PMID 22591951 | RCTRandomised trial | Humann=410 | 24 wk | ↑ SKT, NPI in AD/vascular dementia at 240 mg | Tier B |
| Barton 2013 (PMID 23853036)Panax Ginseng (Korean / Asian Ginseng)PMID 23853036 | RCT (P. quinquefolius)Randomised trial | Humann=364 | 8 wk | ↓ Cancer-related fatigue by 2× vs placebo | Tier B |
| Vuksan 2000 (PMID 10796575)Panax Ginseng (Korean / Asian Ginseng)PMID 10796575 | CrossoverCrossover | Humann=10 T2D | Acute | ↓ Postprandial glucose 15–20% | Tier B |
| Reay 2005 (PMID 15982990)Panax Ginseng (Korean / Asian Ginseng)PMID 15982990 | Acute crossoverCrossover | Humann=27 | Single dose | ↑ Cognitive performance + ↓ glucose | Tier B |
| Ellis Meta 2002 (PMID 12203262)Panax Ginseng (Korean / Asian Ginseng)PMID 12203262 | Meta-analysisMeta-analysis | Not statedn=Various | 8–12 wk | Modest cognitive/wellbeing benefit; heterogeneous | Tier C |
| Katzenschlager 2004 (PMID 15489397)Mucuna Pruriens (Velvet Bean, L-DOPA)PMID 15489397 | Crossover RCTRandomised trial | Humann=8 PD | Acute | Comparable to L-DOPA/carbidopa, less dyskinesia | Tier B |
| Cassani 2016 (PMID 27080066)Mucuna Pruriens (Velvet Bean, L-DOPA)PMID 27080066 | RCTRandomised trial | Humann=18 PD | 4 wk | ↑ UPDRS motor score | Tier B |
| Shukla 2010 (PMID 20080417)Mucuna Pruriens (Velvet Bean, L-DOPA)PMID 20080417 | RCT (male infertility)Randomised trial | Humann=60 | 12 wk | ↓ Cortisol, ↑ semen quality | Tier B |
| Manyam 2004 (PMID 15551964)Mucuna Pruriens (Velvet Bean, L-DOPA)PMID 15551964 | PreclinicalPreclinical | Preclinicaln=Rat | — | Neuroprotection in 6-OHDA model | Tier C |
| Usmani 2005 (PMID 15626761)TheobrominePMID 15626761 | CrossoverCrossover | Humann=10 | Acute | ↓ Capsaicin cough > codeine 60 mg | Tier B |
| Baba 2007 (PMID 17324195)TheobrominePMID 17324195 | RCTRandomised trial | Humann=40 | Acute | ↑ Endothelium-dependent vasodilation | Tier C |
| Neufingerl 2013 (PMID 23407310)TheobrominePMID 23407310 | RCTRandomised trial | Humann=152 | 4 wk | ↑ HDL-C 4%; no effect on BP or endothelial function | Tier C |
| Mitchell 2011 (PMID 21159786)TheobrominePMID 21159786 | CrossoverCrossover | Humann=20 | Acute | ↓ SBP 5 mmHg 2h post-dose | Tier C |
| Lv 2015 China Kadoorie (PMID 26232331)Capsaicin (Cayenne / Chili)PMID 26232331 | Prospective cohortObservational | Humann=487,375 | 7.2 yr | 14% ↓ all-cause mortality; ↓ cancer, IHD, respiratory | Tier B |
| Chopan 2017 (PMID 28068423)Capsaicin (Cayenne / Chili)PMID 28068423 | NHANES IIIObservational | Humann=16,179 | 18.9 yr | 13% ↓ all-cause mortality | Tier B |
| Whiting 2012 meta (PMID 22452938)Capsaicin (Cayenne / Chili)PMID 22452938 | Meta of 20 RCTsMeta-analysis | Human | Acute | ↑ Energy expenditure ~50 kcal; ↓ appetite | Tier B |
| Ludy 2011 (PMID 21093467)Capsaicin (Cayenne / Chili)PMID 21093467 | RCTRandomised trial | Humann=25 | 6 wk | ↑ Fat oxidation, ↓ energy intake in habitual users | Tier C |
| Derry 2012 CochraneCapsaicin (Cayenne / Chili) | Meta (topical)Meta-analysis | Not statedn=2,073 | 12 wk | Topical 8% high-conc effective in neuropathic pain | Tier A |
| Vahlensieck 2015 GRANU (PMID 25874948)Pumpkin Seed OilPMID 25874948 | RCTRandomised trial | Humann=476 BPH | 12 mo | ↓ IPSS 5.0 vs 3.8; well-tolerated | Tier B |
| Cho 2014 (PMID 24864154)Pumpkin Seed OilPMID 24864154 | RCTRandomised trial | Humann=76 AGA men | 24 wk | +40% mean hair count vs placebo | Tier B |
| Bach 2000 (PMID 10774316)Pumpkin Seed OilPMID 10774316 | RCT (seed oil)Randomised trial | Humann=60 BPH | 3 mo | Modest IPSS improvement | Tier C |
| Nishimura 2014 (PMID 25017249)Pumpkin Seed OilPMID 25017249 | RCTRandomised trial | Humann=45 OAB women | 6 wk | ↑ Overactive bladder symptom score | Tier B |
| Muth 2004 (PMID 15340389)Superoxide Dismutase (SOD, Oral GliSODin)PMID 15340389 | Open-labelOpen-label / pilot | Not statedn=30 | 30 d | ↑ SOD activity 39%; ↓ MDA 22% | Tier C |
| Skarpańska 2011 (PMID 21437153)Superoxide Dismutase (SOD, Oral GliSODin)PMID 21437153 | RCT (rowers)Randomised trial | Humann=19 | 6 wk | ↓ Post-exercise oxidative markers | Tier C |
| Egoumenides 2014 (PMID 24829546)Superoxide Dismutase (SOD, Oral GliSODin)PMID 24829546 | RCTRandomised trial | Humann=90 metsyn | 12 wk | ↓ Fasting glucose; ↑ oxidative status | Tier C |
| Coudreuse 2016 (PMID 27057260)Superoxide Dismutase (SOD, Oral GliSODin)PMID 27057260 | RCTRandomised trial | Humann=60 dermatology | 3 mo | ↓ Melasma area with GliSODin + BC | Tier C |
| Shoba 1998 (PMID 9619120)Piperine (BioPerine)PMID 9619120 | CrossoverCrossover | Humann=10 | Acute | 20× ↑ curcumin AUC with 20 mg piperine | Tier A(mechanism) |
| Kesarwani 2013 (PMID 24074601)Piperine (BioPerine)PMID 24074601 | PharmacokineticPharmacokinetic | Not statedn=8 | Acute | 15× ↑ resveratrol AUC | Tier B |
| Bano 1991 (PMID 1907260)Piperine (BioPerine)PMID 1907260 | PharmacokineticPharmacokinetic | Not statedn=Healthy | Acute | Piperine ↑ propranolol AUC 2-fold | Warning |
| Volak 2013 (PMID 23386705)Piperine (BioPerine)PMID 23386705 | Human PKPharmacokinetic | Humann=12 | Acute | Piperine modulates UGT, CYP3A4 activity | Tier A(mechanism) |
| Vandenberghe 2017 (PMID 28633094)MCT Oil (Medium-Chain Triglycerides / C8:C10)PMID 28633094 | Dose-response | Not statedn=9 | Acute | C8 MCT 3× ketone response vs coconut oil | Tier B |
| Cunnane 2020 (PMID 32279606)MCT Oil (Medium-Chain Triglycerides / C8:C10)PMID 32279606 | RCT (MCI)Randomised trial | Humann=83 | 6 mo | ↑ Episodic memory, processing speed; ↑ brain ketone uptake on PET | Tier B |
| Henderson 2009 (PMID 19664276)MCT Oil (Medium-Chain Triglycerides / C8:C10)PMID 19664276 | RCT (AD)Randomised trial | Humann=152 | 90 d | ↑ ADAS-Cog in APOE4-negative subgroup | Tier B |
| Mumme 2015 meta (PMID 25636220)MCT Oil (Medium-Chain Triglycerides / C8:C10)PMID 25636220 | MetaMeta-analysis | Not statedn=749 | 3–24 wk | Modest weight reduction; small effect | Tier C |
| St-Pierre 2019 (PMID 31088732)MCT Oil (Medium-Chain Triglycerides / C8:C10)PMID 31088732 | RCT (endurance)Randomised trial | Humann=14 | 2 wk | ↑ Fat oxidation, unchanged performance | Tier C |
| Stough 2001 (PMID 11498727)Bacopa Monnieri (Brahmi)PMID 11498727 | RCTRandomised trial | Humann=46 | 12 wk | ↑ Verbal learning rate; ↓ recall interference | Tier B |
| Morgan meta 2010 (PMID 20590480)Bacopa Monnieri (Brahmi)PMID 20590480 | Meta of 6 RCTsMeta-analysis | Human | 12 wk | Consistent ↑ delayed word recall | Tier B |
| Peth-Nui 2012 (PMID 23320226)Bacopa Monnieri (Brahmi)PMID 23320226 | RCTRandomised trial | Humann=60 | 12 wk | ↑ Working memory; ↑ attention | Tier B |
| Kongkeaw meta 2014 (PMID 24252493)Bacopa Monnieri (Brahmi)PMID 24252493 | Meta of 9 RCTsMeta-analysis | Humann=437 | 8–24 wk | ↑ Attention, cognitive processing speed | Tier B |
| Sathyanarayanan 2013 (PMID 24101720)Bacopa Monnieri (Brahmi)PMID 24101720 | Preclinical ratPreclinical | Preclinical | 12 wk | ↑ Hippocampal BDNF, ↑ CREB | Tier C |
| Chen 2010 (PMID 20804807)Cordyceps (Cordyceps militaris / sinensis)PMID 20804807 | RCT (older adults)Randomised trial | Humann=20 | 12 wk | ↑ VO₂max threshold 10.5% | Tier C |
| Hirsch 2017 (PMID 27408835)Cordyceps (Cordyceps militaris / sinensis)PMID 27408835 | RCT (recreational)Randomised trial | Humann=28 | 1–3 wk | Small trend; not significant | Tier C |
| Nagata 2006 (PMID 16789952)Cordyceps (Cordyceps militaris / sinensis)PMID 16789952 | RCT (male fertility)Randomised trial | Humann=40 | 8 wk | ↑ Sperm motility | Tier C |
| Preclinical (multiple)Cordyceps (Cordyceps militaris / sinensis) | Mouse / cellPreclinical | Preclinical | — | AMPK, PGC-1α, β-glucan immune signals | Tier C |
| Jin 2016 Cochrane (PMID 27272893)Reishi (Ganoderma lucidum)PMID 27272893 | Meta-analysisMeta-analysis | Not statedn=5 RCTs | Various | No survival benefit alone; ↑ response with chemo | Tier C |
| Chu 2012 (PMID 22995673)Reishi (Ganoderma lucidum)PMID 22995673 | RCTRandomised trial | Humann=26 | 4 wk | ↓ Total cholesterol modestly | Tier C |
| Klupp 2016 meta (PMID 26914009)Reishi (Ganoderma lucidum)PMID 26914009 | Meta of RCTs (diabetes)Meta-analysis | Humann=5 RCTs | 12–16 wk | No significant HbA1c or fasting glucose reduction | Tier C |
| Traditional useReishi (Ganoderma lucidum) | — | Not stated | — | Millennia of use as adaptogen and immune support | — |
| Oba 2007 (PMID 17351811)Turkey Tail (Trametes versicolor, PSK / PSP)PMID 17351811 | Meta of 8 RCTs (gastric)Meta-analysis | Humann=Thousands | Years | ↑ 5-year survival OR 0.71 | Tier B |
| Sakamoto 2006 (PMID 16565629)Turkey Tail (Trametes versicolor, PSK / PSP)PMID 16565629 | Meta (colorectal)Meta-analysis | Not statedn=~3,700 | Years | ↓ Mortality ~11% absolute | Tier B |
| Torkelson 2012 (PMID 22690267)Turkey Tail (Trametes versicolor, PSK / PSP)PMID 22690267 | Small RCT (breast)Randomised trial | Humann=34 | 6 wk | ↑ NK/lymphocyte counts post-radiation | Tier C |
| Chay 2017 (PMID 28282800)Turkey Tail (Trametes versicolor, PSK / PSP)PMID 28282800 | RCT (colon adjuvant)Randomised trial | Humann=129 | 2 yr | ↑ Overall survival with PSK adjunct | Tier B |
| Salvador 2016 (PMID 27409352)Astragalus (Astragalus membranaceus)PMID 27409352 | RCT (TA-65)Randomised trial | Humann=63 | 12 mo | Preserved mean telomere length; ↑ NK cells | Tier C |
| Xu 2014 meta (PMID 24548648)Astragalus (Astragalus membranaceus)PMID 24548648 | Meta (chemo tolerability)Meta-analysis | Not statedn=34 RCTs | Various | ↓ Nausea, neutropenia in cancer chemotherapy | Tier C |
| Bernardes 2011 (PMID 22102734)Astragalus (Astragalus membranaceus)PMID 22102734 | Preclinical (mice)Preclinical | Preclinical | Lifespan | Modest healthspan gain | Tier C |
| Piao 2004 (PMID 15462180)Astragalus (Astragalus membranaceus)PMID 15462180 | RCT (CKD)Randomised trial | Humann=154 | 6 mo | Slowed CKD progression in diabetic nephropathy | Tier C |
| Loguercio 2012 (PMID 22240442)Milk Thistle (Silymarin / Silybin)PMID 22240442 | RCT (NAFLD)Randomised trial | Humann=138 | 12 mo | ↓ Steatosis, ↓ ALT, ↑ insulin sensitivity | Tier B |
| Huseini 2006 (PMID 17094080)Milk Thistle (Silymarin / Silybin)PMID 17094080 | RCT (T2D)Randomised trial | Humann=51 | 4 mo | ↓ HbA1c 1.0pp vs placebo | Tier B |
| Anushiravani 2019 meta (PMID 30589427)Milk Thistle (Silymarin / Silybin)PMID 30589427 | Meta of NAFLD RCTsMeta-analysis | Humann=8 studies | 3–12 mo | Modest ALT/AST reduction; heterogeneous | Tier B |
| Ferenci 1989 (PMID 2671116)Milk Thistle (Silymarin / Silybin)PMID 2671116 | RCT (cirrhosis)Randomised trial | Humann=170 | 41 mo | ↓ Mortality in early cirrhosis, but effect lost in later trials | Tier C |
| Kim 2006 (PMID 16309928)MSM (Methylsulfonylmethane)PMID 16309928 | RCT (knee OA)Randomised trial | Humann=50 | 12 wk | ↓ WOMAC pain, function at 6 g/day | Tier B |
| Debbi 2011 (PMID 21708034)MSM (Methylsulfonylmethane)PMID 21708034 | RCT (knee OA)Randomised trial | Humann=49 | 12 wk | ↓ WOMAC 25% vs 4% placebo at 3.4 g/day | Tier B |
| Brien 2011 meta (PMID 21708034)MSM (Methylsulfonylmethane)PMID 21708034 | Meta of OA RCTsMeta-analysis | Humann=6 studies | 12 wk | Modest, consistent pain reduction | Tier B |
| Muizzuddin 2013 (PMID 24127226)MSM (Methylsulfonylmethane)PMID 24127226 | Small RCT (skin)Randomised trial | Humann=20 | 16 wk | ↑ Skin firmness, ↓ wrinkling | Tier C |
| Kalman 2012 (PMID 22908595)MSM (Methylsulfonylmethane)PMID 22908595 | RCT (recovery)Randomised trial | Humann=40 | Acute | ↓ CK, ↓ DOMS post-exercise | Tier C |
| Fransen LEGS 2015 (PMID 25574023)Chondroitin SulfatePMID 25574023 | RCT (knee OA)Randomised trial | Humann=605 | 2 yr | ↓ Joint-space narrowing with glucosamine + CS | Tier B |
| Hochberg MOVES 2016 (PMID 26686842)Chondroitin SulfatePMID 26686842 | RCT (severe OA)Randomised trial | Humann=606 | 6 mo | Chondroitin + glucosamine = celecoxib for pain | Tier B |
| Reginster 2017 (PMID 28379481)Chondroitin SulfatePMID 28379481 | RCTRandomised trial | Humann=604 | 2 yr | Pharma-grade CS 800 mg ↓ pain, JSN | Tier B |
| Wandel 2010 (PMID 20847017)Chondroitin SulfatePMID 20847017 | Network metaMeta-analysis | Not statedn=Various | Various | Small effect; some concluded no clinical benefit | Tier C |
| Crowley 2009 (PMID 19856234)UC-II (Undenatured Type II Collagen)PMID 19856234 | RCT (UC-II vs G+C)Randomised trial | Humann=52 | 90 d | UC-II 33% WOMAC ↓ vs 14% G+C | Tier B |
| Lugo 2016 (PMID 27614638)UC-II (Undenatured Type II Collagen)PMID 27614638 | RCT (placebo + G+C comparator)Randomised trial | Humann=191 | 180 d | UC-II ↓ pain, stiffness, function significantly | Tier B |
| Trentham 1993UC-II (Undenatured Type II Collagen) | RCT (RA)Randomised trial | Humann=60 | 3 mo | Reduced disease activity | Tier C |
| Bagchi 2002 (biomarker)UC-II (Undenatured Type II Collagen) | Human PKPharmacokinetic | Humann=Small | Acute | Demonstrated intact UC-II reaches gut lymphoid | Tier B(mechanism) |
| Kerkhoffs 2004 (PMID 15150435)BromelainPMID 15150435 | RCT (ankle sprain)Randomised trial | Humann=90 | 14 d | Faster pain/swelling resolution | Tier B |
| Guo 2018 meta (PMID 30319719)BromelainPMID 30319719 | Meta (sinusitis)Meta-analysis | Not statedn=Multiple | Various | ↓ Symptom duration + severity | Tier B |
| Braun 2005 (RCT)Bromelain | RCT (knee OA)Randomised trial | Humann=90 | 12 wk | ↓ Pain + stiffness at 240 mg | Tier B |
| Brien 2004 meta (PMID 15140254)BromelainPMID 15140254 | Meta (OA)Meta-analysis | Not statedn=4 RCTs | 4–12 wk | Modest OA pain reduction | Tier C |
| Papakostas 2012 (PMID 22945484)Methylfolate (L-5-MTHF / L-Methylfolate)PMID 22945484 | RCT (depression)Randomised trial | Humann=148 | 60 d | ↑ SSRI response with 15 mg L-MTHF | Tier B |
| Willems 2004 (PMID 15342466)Methylfolate (L-5-MTHF / L-Methylfolate)PMID 15342466 | Crossover (MTHFR)Crossover | Humann=Variant carriers | Weeks | ↓ Homocysteine 20% more than folic acid | Tier B |
| Rimm 1998 (PMID 9459468)Methylfolate (L-5-MTHF / L-Methylfolate)PMID 9459468 | Cohort (Nurses)Observational | Humann=80,000 | 14 yr | Folate + B6 intake → ↓ CV mortality | Tier A |
| MRC Vitamin Study 1991Methylfolate (L-5-MTHF / L-Methylfolate) | RCT (NTD prevention)Randomised trial | Humann=1,817 | Pre-conception | ↓ NTD recurrence 72% | Tier A |
| Kuzminski 1998 (PMID 9694707)Methylcobalamin (Active B12)PMID 9694707 | RCT (oral vs IM)Randomised trial | Humann=33 | 4 mo | Oral 2 mg = IM for serum B12 | Tier A |
| Yamashiki 1992 (PMID 1408468)Methylcobalamin (Active B12)PMID 1408468 | Various | Not stated | Various | Methylcobalamin for diabetic neuropathy — Japanese use | Tier B |
| Bunn 2014 review (PMID 24983358)Methylcobalamin (Active B12)PMID 24983358 | SystematicMeta-analysis | Not stated | — | B12 deficiency prevalence + treatment | Tier A |
| Sun 2022 (PMID 35367082)Methylcobalamin (Active B12)PMID 35367082 | Meta (diabetic neuropathy)Meta-analysis | Not statedn=Various | 12+ wk | Methylcobalamin ↓ neuropathic symptoms | Tier B |
| Merete 2008 (PMID 18606712)P5P (Pyridoxal-5-Phosphate, Active B6)PMID 18606712 | Observational (NHANES)Observational | Humann=2,800 | Cross-sectional | ↓ hs-CRP with higher B6 status | Tier B |
| HOPE-2 (Lonn 2006, PMID 16531614)P5P (Pyridoxal-5-Phosphate, Active B6)PMID 16531614 | RCT (Hcy)Randomised trial | Humann=5,522 | 5 yr | Folate + B12 + B6 ↓ Hcy but not CV events | Tier A |
| VITATOPS (2010, PMID 20807740)P5P (Pyridoxal-5-Phosphate, Active B6)PMID 20807740 | RCT (stroke)Randomised trial | Humann=8,164 | 3.4 yr | Same combo ↓ Hcy but not stroke recurrence | Tier A |
| Vazquez 2020 (PMID 32013204)P5P (Pyridoxal-5-Phosphate, Active B6)PMID 32013204 | Diabetic neuropathy metaMeta-analysis | Not statedn=Various | 8–24 wk | B12 + P5P combo ↓ neuropathic symptoms | Tier B |
| Stracke 2001 (PMID 11289661)Benfotiamine (Fat-Soluble B1)PMID 11289661 | RCT (DPN)Randomised trial | Humann=40 | 3 wk | ↑ Nerve conduction | Tier B |
| Haupt 2005Benfotiamine (Fat-Soluble B1) | RCT (DPN)Randomised trial | Humann=165 | 6 wk | ↓ Neuropathy symptom score | Tier B |
| Stirban 2006 (PMID 16723522)Benfotiamine (Fat-Soluble B1)PMID 16723522 | Acute RCT (T2D)Randomised trial | Humann=13 | Acute | Prevented post-meal endothelial dysfunction | Tier B |
| BENDIP 2008 (PMID 18313522)Benfotiamine (Fat-Soluble B1)PMID 18313522 | RCT (DPN)Randomised trial | Humann=133 | 6 wk | Modest ↓ neuropathy pain | Tier B |
| Alkhalaf 2010 (PMID 20573793)Benfotiamine (Fat-Soluble B1)PMID 20573793 | RCT (early diabetic nephropathy)Randomised trial | Humann=82 | 12 wk | **Negative** for reducing UAE / renal markers | Tier C |
| Berge & Canner 1991 (PMID 2044644)Niacin (Nicotinic Acid, Vitamin B3)PMID 2044644 | RCT (post-MI), CDP niacin armRandomised trial | Humann=3,908 | 6 yr | ↓ Non-fatal MI recurrence | Tier A |
| Canner 1986 (PMID 3782631)Niacin (Nicotinic Acid, Vitamin B3)PMID 3782631 | 15-yr CDP follow-up | Not statedn=8,341 | 15 yr | ↓ All-cause mortality 11% | Tier A |
| AIM-HIGH 2011 (PMID 22085343)Niacin (Nicotinic Acid, Vitamin B3)PMID 22085343 | RCT (statin + niacin)Randomised trial | Humann=3,414 | 3 yr | **No benefit; excess AE** | Tier A |
| HPS2-THRIVE 2014 (PMID 25014686)Niacin (Nicotinic Acid, Vitamin B3)PMID 25014686 | RCT (statin + niacin/laropiprant)Randomised trial | Humann=25,673 | 4 yr | **No benefit; 4× serious AE** | Tier A |
| Padayatty 2004 (PMID 15068981)Vitamin C (Ascorbic Acid)PMID 15068981 | PharmacokineticPharmacokinetic | Not statedn=Small | Acute | Plasma saturation at 200 mg BID oral | Tier A |
| PHS-II 2008 (PMID 18997197)Vitamin C (Ascorbic Acid)PMID 18997197 | RCT (long-term prevention)Randomised trial | Humann=14,641 | 8 yr | **No CV benefit** with 500 mg/day | Tier A(neg) |
| WACS 2007 (PMID 17698683)Vitamin C (Ascorbic Acid)PMID 17698683 | RCT (women CV)Randomised trial | Humann=8,171 | 9.4 yr | **No CV benefit** in women at high CV risk | Tier A(neg) |
| Cochrane 2013 common coldVitamin C (Ascorbic Acid) | MetaMeta-analysis | Not statedn=Various | Various | Modest ↓ duration in athletes/cold-exposed; **no prevention** in general | Tier B |
| Chen 2008 (PMID 18678913)Vitamin C (Ascorbic Acid)PMID 18678913 | Preclinical + case seriesObservational | Mixed | — | IV pharmacologic dose selectively kills cancer cells in vitro | Tier C |
| SELECT 2011 (PMID 21990298)Mixed Tocopherols (Full-Spectrum Vitamin E)PMID 21990298 | RCT (α-tocopherol)Randomised trial | Humann=35,533 | 7 yr | **↑ Prostate cancer risk 17%** | Tier A(harm) |
| HOPE 2000 (PMID 10639539)Mixed Tocopherols (Full-Spectrum Vitamin E)PMID 10639539 | RCT (α-tocopherol)Randomised trial | Humann=9,541 | 4.5 yr | **No CV benefit** | Tier A |
| Miller 2005 (PMID 15537682)Mixed Tocopherols (Full-Spectrum Vitamin E)PMID 15537682 | Meta of 19 RCTsMeta-analysis | Humann=Various | Years | ↑ Mortality with ≥400 IU α-tocopherol | Tier A(harm) |
| Devaraj 2005 (metsyn)Mixed Tocopherols (Full-Spectrum Vitamin E) | RCT (mixed vs α)Randomised trial | Humann=Small | Weeks | Mixed reduced lipid peroxidation; α did not | Tier C |
| Loguercio 2012 NASHMixed Tocopherols (Full-Spectrum Vitamin E) | RCTRandomised trial | Humann=138 | 12 mo | Vitamin E + silybin + phospholipid reduced steatosis | Tier B |
| Zimmermann 2006 (PMID 16648262)IodinePMID 16648262 | RCT (children, mild deficiency)Randomised trial | Humann=310 | 24 wk | ↑ Cognitive performance, IQ | Tier A |
| Bath 2013 (PMID 23706508)IodinePMID 23706508 | Observational (UK pregnancy)Observational | Not statedn=1,040 | 8 yr child f/u | Mild maternal iodine deficiency → ↓ child cognitive scores | Tier A |
| Aguayo 2013 pregnancyIodine | ReviewReview | Not stated | — | Iodine deficiency in pregnancy → neurodevelopmental impact | Tier A |
| Ghent 1993 (fibrocystic)Iodine | RCTRandomised trial | Humann=1,365 | 6 mo | Molecular iodine ↓ fibrocystic breast pain | Tier B |
| Deutz 2013 (PMID 23809521)HMB (β-Hydroxy β-Methylbutyrate)PMID 23809521 | RCT (older adults, bed rest)Randomised trial | Humann=24 | 10 d | HMB fully preserved lean mass vs 2 kg loss | Tier B |
| Wu 2015 meta (PMID 25553771)HMB (β-Hydroxy β-Methylbutyrate)PMID 25553771 | Meta of 7 RCTsMeta-analysis | Humann=287 | Various | ↑ Lean mass, ↑ functional outcomes | Tier B |
| Bear 2019 meta (PMID 31150038)HMB (β-Hydroxy β-Methylbutyrate)PMID 31150038 | Meta (ICU)Meta-analysis | Not statedn=15 RCTs | Various | ↓ ICU-acquired weakness markers | Tier B |
| Kim 2016 (PMID 27019027)HMB (β-Hydroxy β-Methylbutyrate)PMID 27019027 | RCT (sarcopenia)Randomised trial | Humann=155 | 12 wk | ↑ Strength, function with HMB + D + protein | Tier B |
| Rathmacher 2020HMB (β-Hydroxy β-Methylbutyrate) | RCT (older adults + exercise)Randomised trial | Humann=117 | 12 wk | Modest ↑ muscle quality with HMB + training | Tier B |
| Wilson 2013 (young athletes)HMB (β-Hydroxy β-Methylbutyrate) | MetaMeta-analysis | Not statedn=Various | Various | Weak / no consistent hypertrophy effect | Tier C |
| Membrez / Auwerx 2024 (PMID 38286830)Trigonelline (Frontier NAD+ Precursor)PMID 38286830 | Preclinical + PoCPreclinical | Preclinicaln=Aged mice + small human | 12 wk (human) | ↑ Muscle NAD+; ↑ mito respiration; ↑ grip strength | Tier B(frontier) |
| Membrez plasma cohortTrigonelline (Frontier NAD+ Precursor) | Cross-sectional (Sardinia)Observational | Humann=Centenarians vs age-matched | — | ↑ Plasma trigonelline in centenarians | Tier B(observational) |
| Coffee/fenugreek intake epidemiologyTrigonelline (Frontier NAD+ Precursor) | Various | Not statedn=Populations | Years | Trigonelline exposure correlates with metabolic health markers | Tier C(confounded) |
| Ulven 2011 (PMID 21688839)Krill Oil (Phospholipid Omega-3)PMID 21688839 | RCT (comparative)Randomised trial | Humann=113 | 7 wk | Krill = fish oil for omega-3 index despite lower mass | Tier B |
| Bunea 2004 (PMID 15656416)Krill Oil (Phospholipid Omega-3)PMID 15656416 | RCT (hyperlipidemic)Randomised trial | Humann=120 | 3 mo | ↓ LDL 32–39%, ↓ TG 27%, ↑ HDL | Tier B |
| Deutsch 2007 (PMID 17439714)Krill Oil (Phospholipid Omega-3)PMID 17439714 | RCT (arthritis)Randomised trial | Humann=90 | 30 d | ↓ WOMAC pain 28%, ↓ CRP 30% | Tier B |
| Skarpańska 2010 (PMID 20406627)Krill Oil (Phospholipid Omega-3)PMID 20406627 | RCT (dyslipidemia)Randomised trial | Humann=76 | 12 wk | Modest lipid improvements | Tier C |
| Paladini 2016 meta (PMID 26890198)PEA (Palmitoylethanolamide)PMID 26890198 | Meta of 12 RCTsMeta-analysis | Humann=1,484 | Various | ↓ Pain intensity ~2 points on 10-scale | Tier B |
| Gugliandolo 2020 (neuropathic pain review)PEA (Palmitoylethanolamide) | SystematicMeta-analysis | Not statedn=Various | Various | Consistent moderate effect in DPN, PHN, sciatica | Tier B |
| Beggiato 2020 (AD/PD review)PEA (Palmitoylethanolamide) | Preclinical + small humanPreclinical | Mixed | — | Neuroprotection mechanism plausible; human data early | Tier C |
| Cordaro 2020 (PMID 32471043)PEA (Palmitoylethanolamide)PMID 32471043 | Preclinical + reviewPreclinical | Preclinical | — | Anti-inflammatory PPAR-α mechanism characterization | Tier A(mechanism) |
| Skaper 2013 mast cell reviewPEA (Palmitoylethanolamide) | SystematicMeta-analysis | Not stated | — | PEA mast cell stabilization documented | Tier A(mechanism) |
| Chen 1999 (PMID 10404492)L-ArgininePMID 10404492 | RCT (ED)Randomised trial | Humann=50 | 6 wk | ↑ Erectile function | Tier B |
| Bode-Böger 2003L-Arginine | RCT (endothelium)Randomised trial | Humann=Small | Weeks | ↑ FMD in dyslipidemia | Tier B |
| Dong 2011 metaL-Arginine | Meta (BP)Meta-analysis | Not statedn=11 RCTs | Various | ↓ SBP ~5 mmHg | Tier B |
| **VINTAGE-MI 2006 (PMID 16391215)**L-ArgininePMID 16391215 | RCT (post-MI)Randomised trial | Humann=153 | Stopped early | **↑ Mortality in arginine arm** | Tier A(harm) |
| Ochiai 2012 (PMID 22732208)L-ArgininePMID 22732208 | Crossover (arginine vs citrulline)Crossover | Humann=8 | Days | Citrulline raised plasma arg more than arg itself | Tier B |
| Sima 2005 (PMID 15616239)Acetyl-L-Carnitine (ALCAR)PMID 15616239 | RCT (DPN)Randomised trial | Humann=1,257 | 52 wk | ↑ Nerve conduction, ↓ pain, ↓ vibration threshold | Tier B |
| Montgomery 2003 meta (PMID 12766374)Acetyl-L-Carnitine (ALCAR)PMID 12766374 | Meta of 21 RCTs (MCI/AD)Meta-analysis | Humann=Thousands | 3–12 mo | Modest cognitive improvement | Tier B |
| Wang 2014 meta (PMID 24451335)Acetyl-L-Carnitine (ALCAR)PMID 24451335 | Meta (depression)Meta-analysis | Not statedn=9 RCTs | 6–24 wk | Comparable to SSRIs; faster onset | Tier B |
| Balercia 2005Acetyl-L-Carnitine (ALCAR) | RCT (fertility)Randomised trial | Humann=60 | 6 mo | ↑ Sperm motility in oligoasthenozoospermia | Tier C |
| Malaguarnera 2011 (PMID 21159786)Acetyl-L-Carnitine (ALCAR)PMID 21159786 | RCT (fatigue elderly)Randomised trial | Humann=66 | 6 mo | ↓ Fatigue scores | Tier C |
11 compounds contribute no rows
These deep-dives discuss their evidence in prose without an evidence table, so there is nothing here to extract. They are listed rather than omitted — a gap you can see is a review queue; a gap you cannot is a silent claim of completeness.