The graded index
Every intervention this site has graded, in one table. Sort it, filter it, or search it. The letter is not a verdict on the substance: it is a statement about the strength of the evidence for one named endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score., which is why the endpoint column sits next to it. Any two records can also be set side by side on the comparison page.
209 graded entities. 14 of them hold an A, which is the point of the scale rather than a defect in it.
| Grade | Intervention | Endpoint the grade rests on | Evidence | Citations | Reviewed |
|---|---|---|---|---|---|
| A | Aerobic exercise (Zone 2) 150 min/week Protocol | VO2max The most oxygen the body can use during all-out exercise, a standard measure of aerobic fitness., objectively measured | Randomized training trials and a meta-analysis A study that pools the numbers from several trials into one combined estimate. of them (VO2max gain) + prognostic cohort meta-analysis (Kodama, context only) | 18580415 17507344 41543030 | July 2026 |
| A | Creatine Monohydrate Supplement | One-repetition-maximum strength, an instrument-recorded functional endpoint | Meta-analyses + RCT Randomized controlled trial: people are assigned to the treatment or a comparison by chance, so the groups differ only in what they received. It is the design that can show cause and effect. | 12560406 11740307 34199420 | September 2026 |
| A | Mediterranean diet + extra-virgin olive oil Protocol | Major cardiovascular events (PREDIMED) | Randomized controlled trial People are assigned to the treatment or a comparison by chance, so the groups differ only in what they received. It is the design that can show cause and effect. (PREDIMED) | 29897866 38431146 31981007 | July 2026 |
| A | Neuromuscular Electrical Stimulation (NMES) after Knee Replacement Device or modality | Early quadriceps strength and mobility after total knee replacement, compared with usual care (dynamometer strength, timed up-and-go) | Randomized controlled trials + meta-analysis of randomized trials | 22095207 32610358 28610968 | September 2026 |
| A | Photobiomodulation to Prevent Oral Mucositis Device or modality | Severe (grade 3 to 4) oral mucositis during head and neck radiotherapy or chemoradiation and stem cell transplant, graded by blinded clinicians | Randomized controlled trials + meta-analysis of randomized trials | 24044799 22884841 22502814 | September 2026 |
| A | Pneumatic Compression (sequential) Protocol | Venous thromboembolism incidence | Meta-analysis of randomized trials (VTE, hard endpoint An outcome that matters directly to a person and is counted without judgment, such as death, heart attack, stroke or fracture.) | 23852609 41997536 12436430 | July 2026 |
| A | Resistance training 2–3×/week Protocol | Objectively measured muscle size and strength | Meta-analysis of randomized trials | 32740889 35228201 37491419 | October 2026 |
| A | Semaglutide Longevity Rx | Cardiovascular death, heart attack and stroke in people with cardiovascular disease or type 2 diabetes | Randomized controlled trials | 37952131 27633186 33567185 | August 2026 |
| A | SGLT2 inhibitors (empagliflozin, dapagliflozin) Longevity Rx | Cardiovascular death, heart-failure hospitalization and kidney-failure progression | Randomized controlled trials | 26378978 31535829 32970396 | August 2026 |
| A | Stool-based colorectal screening (gFOBT and FIT) Device or modality | Colorectal cancer mortality (hard endpoint), graded separately by test | Randomized trials of the screening strategy, by test | 24047060 42254696 39028667 | September 2026 |
| A | Transcranial Magnetic Stimulation (TMS) for Depression Device or modality | Response and remission in treatment-resistant major depression on blinded clinician-rated scales (HAM-D, MADRS) | Randomized controlled trials + meta-analysis of randomized trials | 17573044 20439832 25655160 | September 2026 |
| A | Transcutaneous Vagus Nerve Stimulation Device or modality | Postoperative cognitive dysfunction in older adults having major surgery, on the Montreal Cognitive Assessment | Randomized sham-controlled trials and meta-analyses, by use | 42339645 42104979 42456197 | July 2026 |
| A | VO₂max training (Zone 2 + intervals) Protocol | VO2max, objectively measured | Randomized training trials and meta-analyses of them (VO2max gain) + prognostic cohort meta-analysis (mortality) | 38878596 41543030 42730846 | July 2026 |
| A | Zone 2 aerobic training Device or modality | VO2max (cardiorespiratory fitness), an objective functional measure | Randomized training trials and a meta-analysis of them | 18580415 17507344 41543030 | July 2026 |
| B | Adequate dietary protein (1.2 to 1.6 g/kg/day) Protocol | Lean mass and strength during resistance training | Meta-analysis of randomized trials (Morton) + supporting review | 28698222 26797090 35187864 | July 2026 |
| B | Aged garlic extract (480 mg/day for blood pressure; 2.4 g/day in plaque trials) Protocol | Blood pressure in people with hypertension | Randomized trials + meta-analysis of randomized trials | 23169470 26764326 26764322 | July 2026 |
| B | Alcohol reduction Protocol | Blood pressure in people drinking more than two drinks a day | Observational Research that watches what people already do rather than assigning a treatment. It can show that two things travel together, not that one causes the other. synthesis for the headline; randomized trials and pooled analyses on blood pressure and atrial fibrillation | 30146330 39631226 31893513 | July 2026 |
| B | Amla (Indian Gooseberry, Emblica officinalis) Supplement | Lipid profile improvement (LDL Low-density lipoprotein cholesterol, the cholesterol fraction most closely tied to plaque in the arteries., triglycerides); modest glycemic and anti-inflammatory (CRP) support; endothelial function in metabolic syndrome | RCT + meta-analysis of randomized trials | 36934568 31060549 | July 2026 |
| B | Ashwagandha (standardized root extract) Supplement | Cortisol and stress or anxiety scores in stressed adults | Randomized controlled trials | 23439798 26609282 31517876 | July 2026 |
| B | Ashwagandha standardized root extract 300 mg twice daily Protocol | Self-reported sleep in adults with insomnia and anxiety | Randomized double-blind Neither the participants nor the people assessing them know who received the real treatment until the trial ends. placebo-controlled trial (self-reported outcomes) | 31728244 34559859 23439798 | July 2026 |
| B | Avoiding ultra-processed food Protocol | Short-term energy intake and body weight | Randomized controlled trial (inpatient metabolic ward) | 31105044 38418082 39267249 | July 2026 |
| B | Berberine 1.0 to 1.2 g/day (with meals) Protocol | HbA1c A blood test that reflects average blood sugar over the previous two to three months. and LDL cholesterol in type 2 diabetes | Randomized controlled trial | 18442638 18397984 36467075 | July 2026 |
| B | Berberine HCl Supplement | HbA1c, fasting glucose and LDL cholesterol in type 2 diabetes and dyslipidemia | RCT + meta-analysis of randomized trials | 18397984 25498346 18442638 | July 2026 |
| B | Beta-Alanine Supplement | High-intensity exercise capacity | Meta-analysis of RCTs | 27797728 22270875 | July 2026 |
| B | Blood Flow Restriction Training Device or modality | Muscle strength / hypertrophy (objective, low-certainty) | Meta-analyses of randomized trials | 36190389 31301034 42428806 | July 2026 |
| B | Boswellia serrata Supplement | Osteoarthritis pain and function | Meta-analysis of RCTs | 32680575 29018060 | July 2026 |
| B | Bright Light Therapy for Depression Device or modality | Depression scores, response and remission in winter seasonal depression and non-seasonal major depression on clinician-rated scales (SIGH-SAD, HAM-D, MADRS) | Randomized controlled trials + meta-analysis of randomized trials | 9783557 9783558 9783559 | October 2026 |
| B | Cinnamon (Cassia / Ceylon) Supplement | Fasting glucose and HbA1c | Meta-analysis of RCTs | 24019277 38917435 | July 2026 |
| B | Coenzyme Q10 (CoQ10) Supplement | All-cause mortality and hospitalization in heart failure (Q-SYMBIO) | Randomized controlled trial (Q-SYMBIO) | 25282031 39462324 35608922 | September 2026 |
| B | Collagen Peptides Supplement | Self-reported activity-related joint pain and instrument-measured skin hydration and elasticity | RCTs + meta-analyses (skin) | 18416885 28177710 37551682 | July 2026 |
| B | Concurrent training sequence: resistance before aerobic (same session) Protocol | Lower-body dynamic strength (1RM) and maximal aerobic capacity (VO2max) under concurrent training | Meta-analysis of randomized trials | 28783467 28917030 36776981 | August 2026 |
| B | Custom Foot Orthotics Device or modality | Chronic low back pain and disability, short term (self-report) | Randomized controlled trials + meta-analysis of randomized trials | 28465224 23327838 34201981 | September 2026 |
| B | DASH dietary pattern Protocol | Systolic and diastolic blood pressure (DASH, DASH-Sodium) | Randomized controlled feeding trials (DASH, DASH-Sodium) + meta-analyses of randomized trials | 9099655 11136953 25149893 | August 2026 |
| B | EGCG (Epigallocatechin Gallate / Green Tea Extract) Supplement | LDL cholesterol | Meta-analyses of randomized trials + 12-month RCT | 21715508 22027055 27324590 | July 2026 |
| B | Extracorporeal Shockwave Therapy (ESWT) Device or modality | Chronic plantar heel pain (plantar fasciitis), self-report | Sham-controlled randomized trials + meta-analyses of randomized trials | 25948515 18832341 23813184 | September 2026 |
| B | Fasting-mimicking diet (FMD, 5-day cycles) Protocol | Blood pressure, HbA1c and IGF-1 against an unrestricted diet | Randomized controlled trials + meta-analysis | 28202779 38378685 39970875 | July 2026 |
| B | Fenugreek (Trigonella foenum-graecum) Supplement | Glycemic markers | Meta-analysis of RCTs | 36837450 37762302 36470549 | July 2026 |
| B | Ginkgo Biloba (EGb 761) Supplement | Cognitive symptoms in mild to moderate dementia | Meta-analyses of randomized trials and a randomized trial | 25114079 25506211 39895346 | October 2026 |
| B | Home blood pressure monitoring Device or modality | Blood pressure reduction (validated surrogate) | Meta-analysis of randomized trials | 21115879 20619448 | July 2026 |
| B | HRV Biofeedback Device or modality | Self-reported anxiety | Meta-analyses of randomized trials and a sham-controlled randomized trial | 32385728 41905438 41310318 | October 2026 |
| B | Hyaluronic Acid (Oral) Supplement | Self-reported knee symptoms and instrument-measured skin hydration, elasticity and wrinkle depth | Randomized controlled trials + skin meta-analysis (manufacturer-run) | 23226979 18208600 38234616 | July 2026 |
| B | Inositol (Myo-inositol) Supplement | PCOS metabolic and reproductive measures | Meta-analysis of RCTs | 36703143 35477841 | July 2026 |
| B | Inspiratory Muscle Training Device or modality | Resting systolic blood pressure | RCT + meta-analysis of randomized trials | 34184544 37803506 36107991 | October 2026 |
| B | Ketogenic diet (very-low-carbohydrate) Protocol | Seizure frequency in children and adolescents with drug-resistant epilepsy; longevity and cardiometabolic markers graded separately | Umbrella review and meta-analyses of randomized trials + epilepsy RCTs | 37231411 39097343 41621647 | July 2026 |
| B | MBSR (Mindfulness-Based Stress Reduction) 8-week program Protocol | Self-reported anxiety, depression and pain | Meta-analysis of randomized trials | 24395196 25818837 33428616 | July 2026 |
| B | Melatonin Supplement | Sleep onset timing in delayed sleep phase disorder (B) and jet lag symptoms after flights across five or more time zones (B). In ordinary adult insomnia the effect on sleep onset is a few minutes and the adult-only pooled analysis is null, so that use is C. The antioxidant claim rests on no randomized clinical trial and carries no letter. | Meta-analyses of randomized trials, with per-use rows | 15649737 23691095 16423108 | July 2026 |
| B | Mindfulness meditation for sleep (weekly group course with daily home practice) Protocol | Self-reported sleep quality | Meta-analyses of randomized trials | 30575050 32590218 40100065 | October 2026 |
| B | Mobility and fall-prevention protocols Protocol | Falls in older adults | Meta-analyses of randomized trials | 41110662 41567791 | October 2026 |
| B | Nattokinase Supplement | Resting blood pressure (systolic and diastolic) | Randomized controlled trials | 18971533 27785095 39076715 | October 2026 |
| B | Oat beta-glucan (3 g/day or more) for LDL-C Protocol | LDL cholesterol | Meta-analyses of randomized trials, with a molecular-weight trial | 25411276 27724985 35631184 | October 2026 |
| B | Omega-3. High-dose EPA (icosapent ethyl, 4 g) Supplement | Cardiovascular events and cardiovascular mortality | Randomized controlled trials (REDUCE-IT, GISSI-P) | 30415628 10465168 39900648 | September 2026 |
| B | Photobiomodulation (musculoskeletal) Device or modality | Neck pain and tendinopathy pain (self-report) | Meta-analysis of randomized trials (Chow et al. Lancet 2009, LLLT neck pain) | 19913903 40437920 32680739 | October 2026 |
| B | Plant sterols or stanols 1.6 to 2 g/day Protocol | LDL cholesterol | Meta-analysis of randomized trials | 24780090 | July 2026 |
| B | Pneumatic Lymphatic Compression Device or modality | Limb volume reduction (clinical lymphedema) | Systematic review A review that searches for every study on a question using a method set in advance, then assesses them together. of randomized trials | 41997536 | July 2026 |
| B | Psyllium husk (10 to 15 g/day) for LDL-C Protocol | Total and LDL cholesterol | Meta-analyses of randomized trials, psyllium-specific and genus-level | 38688104 30239559 41366295 | July 2026 |
| B | REHIT / Sprint Interval Training Device or modality | Cardiorespiratory fitness (measured VO2max) in inactive adults | Randomized trials of REHIT; background meta-analyses of sprint and interval training | 22124524 30736402 40689309 | October 2026 |
| B | RIMSO-50 (Dimethyl Sulfoxide Bladder Instillation) Longevity Rx | Self-reported symptoms of interstitial cystitis | Randomized controlled trials + meta-analysis | 3288775 33580603 40205912 | September 2026 |
| B | Saffron (Crocus sativus) Supplement | Depression symptom scales (HAM-D and similar) | Meta-analysis of RCTs | 30036891 38913392 | July 2026 |
| B | Sleep restriction treatment (CBT-I) Protocol | Insomnia: sleep onset, time awake after sleep onset and sleep efficiency, from sleep diaries | Meta-analysis of randomized trials (CBT-I) | 26054060 20469800 | July 2026 |
| B | Sodium reduction to under 2,300 mg/day Protocol | Systolic and diastolic blood pressure (Cochrane meta-analysis) | Meta-analysis of randomized trials (Cochrane) | 23558162 11136953 32094151 | August 2026 |
| B | Structured exercise program after treatment for non-metastatic cancer Protocol | Disease-free survival and overall survival after curative-intent treatment for non-metastatic cancer, structured exercise program against health education or usual care | Meta-analysis of randomized trials | 40450658 42744658 19079628 | October 2026 |
| B | Vitamin D3 Supplement | Use-specific. Fall prevention in older adults and respiratory infection prevention: Grade C, mixed randomized evidence. Fracture prevention with vitamin D3 alone: Grade D, tested and no benefit, in deficient or older adults and in adults not selected for deficiency. Vitamin D3 with calcium in older adults living in institutions: Grade B, replicated The same finding reproduced by a separate research group. A result seen once can be chance or bias; a replicated one is harder to explain away. hard-endpoint benefit in institutions, null in the large community trials. Cancer and cardiovascular prevention in adults not selected for deficiency: Grade D, tested and no benefit. | RCTs + meta-analyses (use-specific) | 1331788 15886381 19797342 | July 2026 |
| B | Whole-food plant-based diet Protocol | LDL cholesterol (and HbA1c in type 2 diabetes) | Randomized controlled trials and meta-analyses of randomized trials (LDL cholesterol, HbA1c); cohort evidence only for events and mortality | 37226630 26508743 38032644 | October 2026 |
| B | Zinc Supplement | Common-cold duration in adults | Meta-analyses of randomized trials and a randomized trial | 22566526 27378206 25888289 | October 2026 |
| C | 40Hz Gamma Sensory Stimulation Device or modality | Structural brain change; cognition unestablished | Systematic review / meta-analysis of randomized trials | 41381439 38515445 38073386 | July 2026 |
| C | 5-HTP (5-Hydroxytryptophan) Supplement | Mood and fatigue measures | Small randomized trials and two pooled analyses, low quality; one large null trial on fatigue | 35940251 11869656 31504850 | July 2026 |
| C | Acarbose Longevity Rx | Progression from impaired glucose tolerance to type 2 diabetes | Randomized controlled trial | 12086760 28917545 | August 2026 |
| C | Acetyl-L-Carnitine (ALCAR) Supplement | Cognition in mild cognitive impairment and mild Alzheimer's disease, and diabetic neuropathy pain | Meta-analyses + RCT | 12598816 32408706 15616239 | July 2026 |
| C | Akkermansia muciniphila Supplement | Surrogate metabolic endpoints (insulin sensitivity, glucose, lipids); no hard longevity endpoint | Randomized controlled trials (small, metabolic endpoints) | 31263284 39879980 32675291 | July 2026 |
| C | Alpha Lipoic Acid (ALA / R-ALA) Supplement | Symptoms of diabetic peripheral neuropathy | Randomized controlled trial | 17065669 22837391 21666939 | July 2026 |
| C | Alpha-GPC (L-Alpha-Glycerylphosphorylcholine) Supplement | Cognitive scores in diagnosed mild cognitive impairment, Alzheimer's disease or diabetes with cognitive decline | RCT + systematic review + safety-association study | 12637119 36683513 34817582 | July 2026 |
| C | Alpha-Lipoic Acid (racemic) 300–600 mg/day Protocol | Glucose and insulin resistance in type 2 diabetes | Randomized controlled trial | 21666939 22837391 17065669 | July 2026 |
| C | Astaxanthin Supplement | Skin moisture and elasticity | Meta-analyses of randomized trials and randomized trials | 34578794 22428137 29941810 | October 2026 |
| C | Audiovisual / Brainwave Entrainment Device or modality | Self-reported anxiety, sleep and pain; cognitive test scores | Systematic review / meta-analysis of randomized trials | 30073406 35842538 41176178 | August 2026 |
| C | Bacopa monnieri standardized extract 300–450 mg/day Protocol | Objective cognitive test performance | Meta-analysis of randomized trials | 24252493 41678913 23320031 | July 2026 |
| C | Beetroot / Dietary Nitrate Supplement | Blood pressure in hypertension | RCT + meta-analysis of randomized trials | 25421976 23596162 39069465 | July 2026 |
| C | Benfotiamine Supplement | Diabetic neuropathy measures | RCT (limited) | 41571333 23701274 15726875 | July 2026 |
| C | Bitter Melon (Momordica charantia) Supplement | Glycemic markers | RCT (limited) | 32951763 30385422 38784554 | July 2026 |
| C | Boswellia + Celery Seed Extract (RestorCel) Supplement | Knee osteoarthritis pain and stiffness (WOMAC, VAS) | Single randomized controlled trial | 39875757 | September 2026 |
| C | Bovine Colostrum Supplement | Intestinal permeability / immune measures | RCT (limited) | 38361147 22253980 25068884 | July 2026 |
| C | Caloric restriction (sustained ~25%) Protocol | Metabolic markers and pace of aging in healthy non-obese adults | Randomized controlled trial (CALERIE-2) | 26187233 37118425 29424490 | July 2026 |
| C | Carnosine Supplement | Glycemic markers; muscle and metabolic measures | RCT (limited) | 39770949 29420997 38172006 | July 2026 |
| C | Choline Supplement | Offspring cognitive and developmental measures | RCT (limited) | 29217669 34962672 23134891 | July 2026 |
| C | Chondroitin Sulfate Supplement | Osteoarthritis pain and function | Randomized trials and meta-analyses of randomized trials | 28533290 30879253 16495392 | October 2026 |
| C | Chromium (Picolinate) Supplement | Glycemic markers | RCT (limited) | 24635480 32730903 25971249 | July 2026 |
| C | Citicoline (CDP-Choline) Supplement | Memory and behavior in chronic cerebral disorders of the elderly | Cochrane meta-analysis + RCTs | 15846601 36678257 8624220 | July 2026 |
| C | Cold Water Immersion Device or modality | Stress at 12 hours, sleep quality and quality of life (self-report) | Systematic review / meta-analysis of randomized trials | 39879231 27631616 26174323 | July 2026 |
| C | CoQ10 (ubiquinone) 300 mg/day Protocol | Major adverse cardiovascular events in chronic heart failure | Randomized controlled trial (Q-SYMBIO) | 25282031 39462324 | July 2026 |
| C | Cordyceps (Cordyceps sinensis / militaris) Supplement | Exercise performance / VO2 surrogate measures | RCT (limited) | 15118196 20804368 41280379 | July 2026 |
| C | Creatine 3–5 g/day Protocol | Objectively measured memory and cognitive test performance | Meta-analyses of randomized trials + randomized trials | 35984306 36644917 36644912 | July 2026 |
| C | Curcumin (Turmeric Extract) Supplement | Systemic inflammatory markers (hs-CRP High-sensitivity C-reactive protein, a blood marker of low-grade inflammation., IL-6) and knee osteoarthritis pain and function, both graded C. The neuroprotection and gut health uses commonly claimed for curcumin carry no citation on this record. | Randomized controlled trials + review | 23038702 25618800 29065496 | July 2026 |
| C | DIM (Diindolylmethane) Supplement | Hormone-metabolism / tissue biomarkers A measurable sign in the body, such as a blood test value, used to track a condition or the effect of a treatment. | RCTs (surrogate endpoints A lab value or measurement used in place of the outcome that matters, such as LDL cholesterol standing in for heart attacks. Moving a surrogate does not always move the outcome.) | 28560655 22075942 15623462 | July 2026 |
| C | DMSO (Dimethyl Sulfoxide) Not counted as a supplement | Solvent sold as a liquid and a gel, marketed for joint pain and, more recently, taken by mouth for longevity. The randomized trials tested it on the skin for joint and tendon pain, with mixed results, and no trial has tested it against aging. | Randomized controlled trials, mixed | 8529985 19380203 18417375 | September 2026 |
| C | Ergothioneine (L-Ergothioneine) Supplement | Verbal learning in mild cognitive impairment | One randomized pilot + observational studies | 27444382 36139790 34673145 | July 2026 |
| C | Exogenous Ketones (Ketone Esters and Salts) Supplement | Blood glucose after a meal or glucose drink | Randomized trials and meta-analyses; markers positive, performance and clinical outcomes null | 35380602 38483543 33367782 | October 2026 |
| C | Exosome Therapy (extracellular vesicles) Device or modality | Facial skin quality (instrument-measured surrogate; small split-face RCTs) | Small RCTs + meta-analysis (aesthetic/dermatology) | 37377400 42403177 42635327 | July 2026 |
| C | Fucoidan Supplement | Glycated serum protein, inflammatory markers and vaccine antibody response | RCTs (small, different extracts) | 39645105 24005608 30312135 | July 2026 |
| C | GABA (Gamma-Aminobutyric Acid) Supplement | Sleep quality, mood and heart-rate variability (self-report and surrogate) | RCTs (small) + systematic review | 38321713 33041752 29856155 | July 2026 |
| C | Glucosamine Sulfate Supplement | Knee osteoarthritis joint-space narrowing and symptoms | RCT + observational cohorts | 32253185 33219063 16495392 | July 2026 |
| C | Glutathione (Oral) Supplement | Glutathione-status and oxidative-stress markers (mixed small trials) | RCTs (small, mixed) | 24791752 21875351 33740389 | July 2026 |
| C | Glycine Supplement | Next-day fatigue after experimental sleep restriction in healthy volunteers | Randomized controlled trial | 22529837 35975308 42232577 | August 2026 |
| C | GlyNAC (Glycine + N-Acetylcysteine) Supplement | Use-specific. In healthy older adults the primary endpoint The one outcome a trial names in advance as its main test. Results on other outcomes carry less weight. was null in the one trial not run by the originating group, a 2-week trial sponsored by a company that holds patents on and markets glycine plus NAC products. In older adults randomized by the originating group for 16 weeks at a far higher dose, glutathione and downstream markers improved; that population was not selected for high oxidative stress, and the 'elevated demand' subgroup comes from the sponsor trial's post hoc analysis. | Randomized controlled trials | 35975308 33783984 35821844 | July 2026 |
| C | Gymnema sylvestre Supplement | Glycemic markers in impaired glucose tolerance, metabolic syndrome and type 2 diabetes | RCTs (small) + meta-analysis (low quality) | 32460589 36580574 28459647 | July 2026 |
| C | Hesperidin Supplement | Inflammatory and endothelial markers (CRP, VCAM-1) | Meta-analyses of randomized trials + RCTs | 30991044 27797708 39279783 | July 2026 |
| C | HMB (Beta-Hydroxy Beta-Methylbutyrate) Supplement | Muscle mass and strength (instrument-measured; mixed by population) | Meta-analyses of randomized trials + RCTs (mixed by population) | 40248035 41934514 34081113 | July 2026 |
| C | Hyperbaric Oxygen (HBOT) · 60 sessions at 2.0 ATA Protocol | Telomere length, senescent T cells and cognitive measures in healthy older adults | Randomized controlled trial | 33206062 32589613 | July 2026 |
| C | Hyperbaric Oxygen Therapy Device or modality | Cognition / vascular (2.0 ATA or higher, 100% oxygen) | Randomized controlled trial | 32589613 11558483 | July 2026 |
| C | Infrared Sauna Device or modality | Cardiovascular / endothelial (surrogate + functional) | Randomized controlled trials | 27001189 15090706 34954348 | July 2026 |
| C | Intermittent fasting (5:2 / alternate-day energy restriction) Protocol | Weight and cardiometabolic markers, compared with daily calorie restriction | Meta-analyses of randomized trials + one-year RCTs | 30583725 28459931 30475957 | July 2026 |
| C | L-Citrulline Supplement | Blood pressure (surrogate); exercise performance stated separately | Meta-analyses of randomized trials + RCT (surrogates) | 30788274 30284051 28940638 | July 2026 |
| C | L-Theanine 200 mg/day Protocol | Self-reported sleep quality | Randomized controlled trial | 31623400 42410082 40056718 | July 2026 |
| C | L-Tyrosine Supplement | Working memory and reaction measures during acute cold or combat stress | Small randomized and controlled trials under acute stress | 38975711 17585971 10230711 | July 2026 |
| C | Lactoferrin Supplement | Respiratory and systemic symptom scores (self-report) and respiratory infection incidence in adults | RCT (limited) | 37764743 31529448 32151562 | July 2026 |
| C | Lion's Mane 3 g/day fruiting-body powder (as studied) Protocol | A cognitive score (HDS-R) in mild cognitive impairment | Randomized controlled trial | 18844328 31413233 32581767 | July 2026 |
| C | Lion's Mane Mushroom Supplement | Cognitive test scores in older adults with mild cognitive impairment | Small randomized trials on measured cognitive tests | 18844328 31413233 36582308 | July 2026 |
| C | Lithium (Low-Dose / Microdose) Supplement | Cognitive decline in mild cognitive impairment and Alzheimer's disease | RCTs + population studies | 28832877 29103043 1699579 | July 2026 |
| C | Low-Dose Naltrexone (LDN) Longevity Rx | Symptoms in Crohn's disease and fibromyalgia | Randomized trials, pooled analysis, and two pilots | 21380937 23359310 42701992 | July 2026 |
| C | Magnesium Supplement | Use-specific. Sleep quality in primary insomnia: Grade C on three small self-report trials pooled at low to very low certainty. Cardiovascular events and all-cause mortality: Grade D, because no randomized trial has tested it; the evidence is observational dietary data. Deficiency is common and correcting a deficiency is not the same claim as supplementing when replete. | RCT + observational meta-analysis | 33865376 23853635 24259558 | July 2026 |
| C | Magnesium bisglycinate 250 mg elemental at bedtime Protocol | Self-reported insomnia severity in adults with poor sleep | One randomized trial of the glycinate form plus systematic reviews of other salts | 33865376 40918053 42661485 | July 2026 |
| C | Melatonin 0.3 to 0.5 mg (low dose), 30 to 60 minutes before bed Protocol | Sleep onset and sleep efficiency at low doses (0.3 to 0.5 mg) | Meta-analysis of randomized trials | 23691095 11600532 29912983 | July 2026 |
| C | Mesenchymal stem cell therapy (intravenous, allogeneic laromestrocel) Device or modality | 6-minute walk distance and physical function in diagnosed aging frailty | Randomized human trials, one at moderate scale, unreplicated | 41747733 28977399 38679727 | August 2026 |
| C | Methylene Blue (low-dose) Supplement | Memory retrieval and contextual memory after a single oral dose | Two small single-dose randomized trials from one laboratory | 25018057 27351678 27284082 | July 2026 |
| C | Milk Thistle (Silymarin) Supplement | Liver enzymes and NAFLD/NASH markers | Randomized trials and a Cochrane review; surrogate endpoint, very low certainty | 38579127 29245314 40552569 | July 2026 |
| C | MitoQ (Mitoquinone Mesylate) Supplement | Brachial artery flow-mediated dilation in older adults | Small randomized trials; surrogate positive, functional outcomes null | 29661838 35623315 20492507 | July 2026 |
| C | Molecular Hydrogen (Inhaled) Device or modality | Condition-specific endpoints, one small trial each: COPD exacerbation symptom score, NAFLD liver fat, sleep scales | Randomized controlled trials, one small trial per indication; the one hard-endpoint trial null | 33985501 35734974 40826930 | July 2026 |
| C | Molecular Hydrogen Water Device or modality | Total and LDL cholesterol in adults with metabolic disorders (small, sub-threshold changes) | Meta-analyses of small randomized trials, inconsistent | 34601077 41888952 39839806 | July 2026 |
| C | Montmorency Tart Cherry Supplement | Actigraphic and self-reported sleep; recovery of muscle strength after exercise | Small randomized trials; two meta-analyses for exercise recovery | 22038497 36011907 39683518 | July 2026 |
| C | Multi-domain diet and lifestyle program with supplements (8 weeks, as studied) Protocol | DNA methylation age, an epigenetic clock A test that estimates biological age from chemical marks on DNA (DNA methylation). | One pilot randomized controlled trial, maker-funded | 33844651 36947707 38488762 | July 2026 |
| C | NAC (N-Acetyl Cysteine) Supplement | Clinician-rated symptom scores in schizophrenia; COPD exacerbation rate | Randomized trials and meta-analyses, mixed results | 31826654 35975308 37712506 | July 2026 |
| C | NMN (Nicotinamide Mononucleotide) Supplement | Muscle insulin sensitivity in prediabetic postmenopausal women, which is the use the Grade C rests on. Blood NAD+ Nicotinamide adenine dinucleotide, a molecule cells use in energy metabolism. Its level falls with age in some tissues. concentration is also Grade C and is a mechanistic marker, not an outcome. Longevity, healthspan and mortality are Grade D: no human trial has tested them. | Randomized controlled trial, single small trial per use | 33888596 41901064 36482258 | July 2026 |
| C | NMN 250–500 mg/day (morning) Protocol | Insulin sensitivity and blood NAD | Randomized controlled trials (Yoshino; Yi) | 33888596 36482258 | July 2026 |
| C | NR (Nicotinamide Riboside) Supplement | Six-minute walk in peripheral artery disease; blood NAD+; cognition and insulin sensitivity tested without benefit; early Parkinson disease tested with harm found | Randomized trials, mostly null on clinical outcomes; one unreplicated positive | 27721479 27725675 29184669 | July 2026 |
| C | Omega-3 EPA/DHA 2 to 4 g/day (general supplementation) Protocol | Cardiovascular events, including coronary death | Meta-analyses of randomized trials (mixed/modest) | 31567003 32114706 30415628 | July 2026 |
| C | Padma Basic (Tibetan multi-herb formula) Supplement | Pain-free and maximum walking distance in intermittent claudication | Cochrane meta-analysis of randomized trials | 27021597 16600251 | July 2026 |
| C | Panax Ginseng Supplement | Erectile function scores (IIEF), self-reported | Cochrane review of small randomized trials; trivial effect at low to moderate certainty | 33871063 41696741 12394711 | July 2026 |
| C | PEMF (Pulsed Electromagnetic Field) for osteoarthritis symptoms Protocol | Self-reported osteoarthritis pain and function | Meta-analyses of sham-controlled trials, mixed (self-reported outcomes) | 30552258 31583420 42075549 | July 2026 |
| C | Pentadecanoic Acid (C15:0) Supplement | LDL cholesterol and liver enzymes (surrogate) | Two small randomized controlled trials | 38035997 39069269 | September 2026 |
| C | Phosphatidylserine (PS) Supplement | Memory and cognition in older adults, graded separately for the bovine-cortex and soy forms | Randomized controlled trials | 8323999 2027477 21103034 | July 2026 |
| C | Power (high-velocity) resistance training versus traditional strength training Protocol | Physical function in adults 60 and over, power versus traditional strength training | Meta-analyses of head-to-head randomized trials, low certainty | 35544136 37328359 36378500 | July 2026 |
| C | PQQ (Pyrroloquinoline Quinone) Supplement | Cognitive test performance in middle-aged and older adults | Randomized controlled trials | 24231099 27526146 26782228 | July 2026 |
| C | Probiotics Supplement | Gut microbiome diversity, immune regulation, inflammation reduction, Akkermansia support, post-antibiotic restoration | RCT + consensus + meta-analysis | 34256014 24912386 30959049 | July 2026 |
| C | Pulsed Electromagnetic Field (PEMF) Device or modality | Knee osteoarthritis pain, self-reported, short term | Meta-analyses of sham-controlled trials, inconsistent; one 2026 sham A fake version of a procedure or device used as the comparison, so participants cannot tell which one they received. trial | 42075549 31583420 30552258 | July 2026 |
| C | Quercetin Supplement | Blood pressure, with lipids and glycemic markers tested without change | Meta-analyses of small randomized trials; blood pressure mixed, lipids and glucose null | 25897620 30848564 27405810 | July 2026 |
| C | Red Light / Near-Infrared (630–850nm) Protocol | Skin aging, knee osteoarthritis pain, diabetic foot ulcer healing and venous leg ulcer healing, each graded on its own row | Meta-analyses of randomized trials + randomized controlled trials | 28748217 24286286 17566756 | July 2026 |
| C | Red Yeast Rice (Monacolin K) Supplement | Major coronary events (nonfatal myocardial infarction and coronary death) after myocardial infarction, one trial; mortality secondary | Randomized controlled trial (hard clinical endpoints) | 18549841 19602720 32066811 | July 2026 |
| C | Reishi (Ganoderma lucidum) Supplement | Immune cell measures and tumor response as an adjunct A treatment tested on top of standard prescribed therapy rather than in place of it. to cancer treatment; cardiometabolic risk factors tested without benefit | Cochrane reviews of small randomized trials; one placebo-controlled trial | 27045603 25686270 27511742 | July 2026 |
| C | Resveratrol (Trans-Resveratrol) Supplement | Metabolic markers in obese men, mixed; exercise training adaptations in older men, blunted | Small randomized trials, mixed; pooled risk factors null; one training trial with harm | 22055504 23193181 23102619 | July 2026 |
| C | Retatrutide Longevity Rx | Body weight and HbA1c | Randomized controlled trials (phase 2 and phase 3) | 37366315 37385280 42250575 | September 2026 |
| C | Rhodiola Rosea Supplement | Fatigue, by test-based fatigue indices and questionnaires | Small randomized trials, mixed; one independent trial found harm on fatigue | 12725561 11081987 10839209 | July 2026 |
| C | SAM-e (S-adenosyl-L-methionine) Supplement | Methyl donor marketed for depression and for osteoarthritis joint pain. Use-specific: as a stand-alone treatment for depression the pooled randomized trials disagree (Grade C); added to an antidepressant, and for osteoarthritis, the pooled trials did not separate from placebo An inactive substitute made to look like the real treatment, so participants cannot tell which one they received. (Grade D). | Randomized trials and meta-analyses, mixed for monotherapy, negative for add-on use | 27727432 38199136 19821403 | September 2026 |
| C | Selenium (Selenomethionine) Supplement | Thyroid peroxidase antibody levels in autoimmune thyroiditis, lower across several meta-analyses and one 412-patient trial, a surrogate whose fall has not changed thyroid function, levothyroxine dose or quality of life (C). Long-term supplementation in adults who are not deficient was tested in trials of 1,312 to 35,533 people: no cancer benefit and a signal of more type 2 diabetes (D Route 2 Human randomized trials have been run and did not show benefit on the stated outcome. One of the two routes to the lowest letter on EBL's scale.). The trials were not selected for selenium deficiency, and the Cochrane review found no clear influence of baseline status on outcomes. | Randomized controlled trials (mixed results) | 8971064 19066370 22626835 | July 2026 |
| C | Sleep duration & quality (as longevity target) Device or modality | Cardiometabolic markers and energy intake after sleep extension in short sleepers | Randomized trials of sleep extension and a meta-analysis of them; mortality data are observational and carry no grade | 34279625 41564347 34459060 | October 2026 |
| C | Sulforaphane (Broccoli Sprout Extract) Supplement | Glucose control and insulin resistance in type 2 diabetes | Randomized controlled trials, small and short, mixed | 22537070 28615356 21559038 | July 2026 |
| C | Taurine Supplement | Use-specific. Endothelial, vascular and inflammatory markers in type 2 diabetes: Grade C, three randomized trials agree, but the markers are not established stand-ins for a clinical outcome. Glycemic control in type 2 diabetes: Grade C, one null and two positive trials at 3 g/day. Acute 3-km running performance: Grade C, one crossover A trial design in which each participant receives both the treatment and the comparison, one after the other, and serves as their own control.. Aging or longevity: no human randomized trial (Route 1 No human randomized trial has been run, so the record rests on animal or mechanistic evidence only. One of the two routes to the lowest letter on EBL's scale.). | Randomized trials on type 2 diabetes markers; animal and observational for aging | 37289866 19239132 22322924 | August 2026 |
| C | Therapeutic plasma exchange (plasmapheresis for aging) Device or modality | Epigenetic clocks and circulating biomarkers of aging | One small single-blinded trial with entry-date allocation; one trial of a different procedure, unfavorable | 40424097 40592961 | August 2026 |
| C | Therapeutic Ultrasound Device or modality | Temporomandibular disorder pain (mixed: pooled analysis favorable, sham-controlled trials null) | Network meta-analysis of randomized trials plus small sham-controlled trials, mixed | 42332459 29767650 37721730 | July 2026 |
| C | Time-restricted eating (early, 6 to 10 hour window) Protocol | Weight and metabolic markers with calories held equal | Randomized controlled trials | 29754952 31813824 41310471 | July 2026 |
| C | Tirzepatide Longevity Rx | Onset of type 2 diabetes in obesity with prediabetes | Randomized controlled trials | 39536238 41406444 | August 2026 |
| C | TMG (Trimethylglycine / Betaine) Supplement | Plasma homocysteine An amino acid in the blood that rises when vitamin B12, folate or B6 are low. | Randomized controlled trials and meta-analyses of randomized trials | 14652361 36717385 12399266 | July 2026 |
| C | Tongkat Ali (Eurycoma longifolia) Supplement | Total testosterone in men with low testosterone, a hormone level | Small randomized trials and one meta-analysis, heterogeneous | 33541567 36013514 34262417 | July 2026 |
| C | Transcendental Meditation (TM) · secondary CVD prevention Protocol | Death, heart attack and stroke in coronary heart disease | Randomized controlled trial | 23149426 38358047 40177279 | July 2026 |
| C | Transcranial Direct Current Stimulation Device or modality | Depressive symptoms in major depression on blinded clinician-rated scales (HAM-D, MADRS), mixed | Randomized sham-controlled trials and meta-analyses, inconsistent | 42435147 41498282 23389323 | July 2026 |
| C | Transcranial Photobiomodulation Device or modality | Cognition (limited human evidence) | Systematic review of randomized trials | 37843594 | July 2026 |
| C | Turkey Tail (Trametes versicolor / PSK) Supplement | Overall survival after curative resection of colorectal or gastric cancer, PSK added to chemotherapy | Randomized trials and meta-analyses in Japanese surgical patients, mixed | 36445793 16133112 17106715 | July 2026 |
| C | Urolithin A Supplement | Muscle endurance, strength and mitochondrial markers, where the pre-registered primary endpoints were missed | Randomized controlled trials | 32694802 35584623 35050355 | July 2026 |
| C | Vitamin D3 2,000–4,000 IU + K2 MK-7 100 mcg Protocol | Bone loss in postmenopausal women, measured for the MK-7 component alone | Randomized controlled trials (MK-7 bone; D3 epigenetic aging) | 23525894 1331788 30256915 | July 2026 |
| C | Vitamin K2 (MK-7 / Menaquinone-7) Supplement | Arterial stiffness and coronary artery calcification | Randomized controlled trial (3-year, arterial stiffness) | 25694037 15514282 42268593 | July 2026 |
| C | Weekly vigorous exercise volume compressed into one session (weekend warrior pattern) Protocol | Fat mass by DXA (primary) and maximal aerobic capacity, VO2max (secondary), under one weekly session against control | Single randomized controlled trial | 41519797 16874148 39921357 | August 2026 |
| C | WGP Beta-1,3/1,6-D-Glucan Supplement | Incidence and duration of upper respiratory tract infections | Randomized controlled trials | 23378458 23340963 28606567 | July 2026 |
| C | Whole Body Vibration Device or modality | Bone mineral density (surrogate, objective) | Randomized trials and meta-analyses of randomized trials | 22084333 25581217 29289937 | October 2026 |
| D | 2-HOBA (2-Hydroxybenzylamine) Supplement | Atrial fibrillation recurrence after ablation | Randomized controlled trial | 40709466 31907026 36935449 | October 2026 |
| D | Apigenin Supplement | No human randomized trial of standalone apigenin has been run. Route 1: cell, animal and mechanistic work only. Proposed as a CD38 inhibitor that preserves NAD+ by blocking its main degrading enzyme, and taken alongside NMN in some longevity protocols on that reasoning. The reasoning is not the evidence: a PubMed search for randomized human trials of apigenin on its own returned none; the one randomized trial that contains apigenin tested a multi-ingredient product. | Mechanistic / preclinical only (D Route 1) | 21641214 23172919 38302501 | July 2026 |
| D | Arterosil HP (Rhamnan Sulfate) Supplement | No randomized trial has tested rhamnan sulfate on plaque or vascular outcomes; one small randomized trial for constipation found no effect on blood lipids. Route 1: one uncontrolled case series plus preclinical data. | Case series + animal only (D Route 1) | 38404609 36332287 34226572 | July 2026 |
| D | Aspirin (low-dose, primary prevention in healthy older adults) Protocol | Disability-free survival in healthy adults aged 70 and over | Randomized controlled trial | 30221595 30221596 30221597 | July 2026 |
| D | Beta-Carotene (supplemental) Supplement | Tested at scale for cancer prevention in six large trials. Beta-carotene alone raised lung cancer in male smokers (ATBC); beta-carotene with retinyl palmitate raised lung cancer and death in smokers and asbestos workers (CARET, stopped early); in mostly non-smoking physicians and women it did nothing. A harm finding in smokers, a null in everyone else. | Randomized controlled trials (harm found → D Route 2) | 8127329 15572756 8602180 | July 2026 |
| D | Boron Supplement | Bone and steroid-hormone markers | No adequate human trials | 32540741 8508192 7889886 | July 2026 |
| D | BPC-157 (Body Protection Compound 157) Supplement | Tendon, ligament and gut tissue healing. No result of a human randomized controlled trial of the compound has been published; the developer group states a phase II trial in inflammatory bowel disease was run, and no result of it is indexed. | Animal study only (D Route 1) | 40756949 40789979 41966639 | July 2026 |
| D | Bromelain Supplement | Osteoarthritis pain and inflammation markers, bromelain alone | RCT (limited) | 40803821 17121765 27412590 | July 2026 |
| D | C60 (Carbon-60 / Buckminsterfullerene) Supplement | No human trial of oral C60 has been run; the only human randomized trials of fullerene are topical. Route 1: animal and mechanistic data only, and the animal studies disagree with each other. C60 in olive oil extended lifespan in a small 2012 rat study that has not been reproduced; a 2021 mouse study found C60-in-oil mice outlived oil-fed controls but not water-fed controls, pointing at the vehicle; another 2021 mouse experiment reported light-dependent toxicity and no lifespan extension. Sold as an antioxidant with no established human use case. | Animal study only (rat lifespan); no human trial → D Route 1 | 22498298 33123847 41861269 | July 2026 |
| D | Calcium Alpha-Ketoglutarate (Ca-AKG) Supplement | No randomized trial of Ca-AKG on an aging outcome has reported. A placebo-controlled trial of 1 g Ca-AKG on a DNA methylation clock (ABLE) has enrolled and not yet reported; an older trial of 6 g AKG calcium in women with osteopenia measured a bone-turnover marker. Route 1 Grade D: animal lifespan data plus one retrospective, uncontrolled report of customers of a multi-ingredient product, measured by a commercial DNA methylation test and authored from the company that sells it. | Animal + uncontrolled human report (D Route 1) | 32877690 34847066 17896582 | July 2026 |
| D | EEG Neurofeedback Device or modality | ADHD symptoms in children and adolescents (self-report, blinding-sensitive) | Sham-controlled RCTs + meta-analyses of randomized trials | 42358407 39661381 32853703 | July 2026 |
| D | Fisetin Supplement | No randomized trial of fisetin as a senolytic A compound intended to clear senescent cells: older cells that have stopped dividing but remain in tissue. for aging has reported results. Small randomized trials exist in other uses, including a null placebo-controlled crossover in Gulf War illness. Route 1: animal senolytic data only. | Animal study only (D Route 1) | 30279143 33802381 29541713 | July 2026 |
| D | Folic Acid (supplemental, 1 mg/day) Supplement | Tested for colorectal adenoma recurrence in three placebo-controlled trials and a pooled analysis of 2,632 patients. No reduction. The largest trial raised the possibility of more advanced neoplasia, and its long-term follow-up found more sessile serrated lesions with extended use; no overall cancer increase was found across 13 trials. | Randomized controlled trials + pooled analysis (no benefit, D Route 2) | 17551129 19864409 18022173 | July 2026 |
| D | General health checks (multi-organ screening of asymptomatic adults) Protocol | All-cause, cardiovascular and cancer mortality in adults unselected for disease | Cochrane meta-analysis of randomized trials (found no mortality benefit → D) | 30699470 24912589 42414985 | July 2026 |
| D | Genetic testing to choose diet or supplements (nutrigenomic panels) Device or modality | Diet quality and health measures with advice tailored to genotype, compared with personalized advice that does not use genotype | One large randomized trial and a meta-analysis of 11 studies | 27524815 36779907 | October 2026 |
| D | Geranylgeraniol (GG) Supplement | No human randomized trial of the statin-muscle claim has reported, and no registered trial of that claim was located in this pass. Route 1 for the statin-muscle use: mechanistic and animal work. GG has now been tested in humans on other endpoints: a 150-person randomized trial found GG alone had no effect on plasma CoQ10 or on health and vitality questionnaires in healthy adults, and a 34-person fixed-order placebo-then-GG study found no change in testosterone overall. Popularity is not evidence: this is taken as a statin adjunct on the strength of a mechanism, not a trial result. | Mechanistic / preclinical only (D Route 1) | 31491372 29951166 42323079 | July 2026 |
| D | Hormone replacement therapy (combined estrogen + progestin, primary prevention) Protocol | Chronic disease in healthy postmenopausal women, including breast cancer, stroke and blood clots | Randomized controlled trial with extended follow-up + systematic reviews | 12117397 24084921 28898378 | July 2026 |
| D | Luteolin Supplement | Olfactory test performance after COVID-19; tested only inside a palmitoylethanolamide combination | Combination RCT only; luteolin alone untested (D Route 1) | 35450527 33802381 38861957 | July 2026 |
| D | Magnesium Glycinate 300–400 mg Protocol | Insulin resistance | No trial of magnesium glycinate on this endpoint (D Route 1); class evidence from other magnesium salts, mixed, shown as context | 28526383 37922013 42426860 | July 2026 |
| D | Magnesium Glycinate 300–400 mg elemental Protocol | Blood pressure | No trial of magnesium glycinate on this endpoint (D Route 1); class evidence from other magnesium salts shown as context | 27402922 35576873 16856052 | July 2026 |
| D | Metformin (for longevity) Longevity Rx | Muscle and mitochondrial gains from exercise training in healthy older adults | Randomized controlled trials | 31557380 30548390 33071237 | August 2026 |
| D | Multi-cancer early detection blood test (cell-free DNA) Device or modality | Incidence of late-stage (III and IV) cancer at diagnosis, a stage-shift surrogate for cancer mortality | Tested in one large randomized trial; primary endpoint not met | 42776074 42773209 39898371 | October 2026 |
| D | NAD+ (Direct Oral Supplementation) Supplement | No randomized trial has tested oral NAD+ itself on a clinical, functional or validated-scale outcome, and a 2026 systematic review found none for oral or intravenous NAD+. The one randomized trial of oral NAD+ (Kornilov 2026) tested a proprietary formulation for 5 days with blood NAD as its primary endpoint; its authors are linked to the formulation's developer. Route 1. The trials commonly cited for NAD+ supplementation are trials of its precursors, NMN and NR, which are different molecules. | No outcome trial; one randomized pharmacokinetic study of a proprietary formulation (D Route 1) | 33888596 35479740 39044608 | July 2026 |
| D | Niacin (extended-release, for lipids) Supplement | Tested at scale on top of statins. Extended-release niacin alone (AIM-HIGH) and extended-release niacin with laropiprant (HPS2-THRIVE) did not reduce vascular events; the laropiprant combination increased serious adverse events. | Two large randomized outcome trials, no benefit (D Route 2) | 25014686 22085343 28616955 | July 2026 |
| D | Omega-3 DHA 1–2 g/day Protocol | Cognitive function in older adults | Randomized controlled trials + meta-analysis of randomized trials | 20434961 22305186 42000571 | July 2026 |
| D | PectaSol Modified Citrus Pectin (MCP) Supplement | PSA kinetics in biochemically relapsed prostate cancer, from single-arm studies only | Single-arm Phase II studies for the prostate use; two null placebo-controlled trials in other uses | 31683865 14663471 22532035 | October 2026 |
| D | Phosphatidylserine 300 mg/day (soy-derived) Protocol | Memory in older adults with memory complaints | Randomized controlled trial | 8323999 21103034 20523044 | July 2026 |
| D | Piperlongumine Supplement | No human trial has been run, and no human dose or safety data exist. Route 1: preclinical senolytic work only. In cultured human fibroblasts, piperlongumine killed senescent cells by apoptosis, and the cited paper reports that this did not require the induction of reactive oxygen species. The authors filed a patent on piperlongumine and its analogs as anti-aging agents, and two are tied to a senolytic company. | Cell-culture / preclinical only (D Route 1) | 27913811 | July 2026 |
| D | Procyanidin C1 (PCC1) Supplement | No human trial has been published. Route 1: mouse and cell work only. The founding mouse study, now under an Expression of Concern from its journal, reported that PCC1 killed senescent cells, possibly by promoting reactive oxygen species and mitochondrial dysfunction; later mouse studies from other groups, for example in the aged retina, report senolytic effects. Nothing in humans. | Animal study only (mouse senescence); no human trial → D Route 1 | 34873338 41731120 38657052 | July 2026 |
| D | Pterostilbene Supplement | LDL cholesterol in adults with raised cholesterol | Randomized controlled trial | 25057276 23431291 40024751 | July 2026 |
| D | Rapamycin (Sirolimus) Longevity Rx | Visceral adiposity and physical function (chair-stand repetitions) in older adults | Three randomized placebo-controlled trials, null primaries (D Route 2) | 40188830 41985884 41524558 | July 2026 |
| D | Reducing anticholinergic drug burden Protocol | Cognition, falls, quality of life and mortality | Observational harm-association study; no deprescribing Reducing or stopping a medication under a prescriber's supervision. RCT demonstrates benefit | 41761231 38063254 37740900 | July 2026 |
| D | Sermorelin (GHRH 1-29) Supplement | One placebo-controlled trial of GHRH(1-29), in healthy older adults (PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 16399214), is under review. Growth hormone and IGF-1 rose in two tiny studies from one research group, one randomizing only the order of two doses and the other uncontrolled; a hormone level shows the drug acted, not that health changed. Body composition, frailty and mortality have no randomized trial of sermorelin itself. All uses D, Route 1. | No placebo-controlled trial; one dose-order study and uncontrolled studies | 1379256 9005976 7955460 | October 2026 |
| D | Serrapeptase (Serratiopeptidase) Supplement | Postoperative swelling (measured) and pain (self-reported) | Small randomized trials, narrow postoperative indications only | 33653320 6366808 18272344 | October 2026 |
| D | Spermidine Supplement | No randomized trial of spermidine on lifespan or mortality has been run. A 12-month randomized trial in older adults with subjective cognitive decline (SmartAge) found no effect on memory. Route 1: animal lifespan data plus observational epidemiology. | Animal + observational for aging (D Route 1); randomized trial null for memory (D Route 2); pharmacokinetic trials | 27841876 29955838 35616942 | July 2026 |
| D | Trehalose Supplement | Proposed autophagy The process cells use to break down and recycle their own worn-out parts. inducer, untested for that claim in people. The one oral trial in healthy middle-aged and older adults (100 g/day for 12 weeks) found no significant change in its primary vascular measure in the full sample, and an intravenous trial in heart attack survivors found no change in arterial inflammation. | Animal mechanism + small human randomized trials, null on the primary analysis | 26905426 27208415 35045351 | July 2026 |
| D | Vascanox HP (Nitric Oxide / Noxa24) Supplement | No randomized trial has been run. Route 1: one open-label Everyone in the trial knows which treatment they are receiving, so expectations can shape the results, especially for symptoms people report themselves., uncontrolled trial of the branded formula. | Single open-label uncontrolled study; no randomized trial | 37849591 | July 2026 |
| D | Vitamin E (supplemental alpha-tocopherol) Supplement | Tested at scale for cancer prevention with no benefit in any large trial. In SELECT, 400 IU/day of synthetic vitamin E significantly increased prostate cancer in healthy men on extended follow-up; a second large trial in healthy men at 400 IU every other day found no prostate effect either way. | Large randomized trials and pooled reviews, no benefit, harm signal in one trial | 21990298 8127329 19066368 | July 2026 |
| D | Whole-body MRI screening (asymptomatic adults) Device or modality | Cancer mortality or all-cause mortality in asymptomatic screened adults | No randomized outcome trial; pooled observational yield data only | 32393345 30932247 40884613 | August 2026 |
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