A source-linked guide to the evidence grades for 15 supplements and interventions. These grades summarize the strength and limits of the cited research; they are not personal predictions.
What the grades mean
A: strong evidence
B: good evidence
C: early or limited evidence
CoQ10
A
Evidence is strongest for selected heart-failure outcomes; it does not establish a general lifespan benefit.
Key evidence
Systematic review and meta-analysis — Evaluating the efficacy of ubiquinol in heart failure patients (2024): A review of 16 studies in heart-failure patients reported improved exercise capacity and lower heart-failure mortality; this population-specific result does not establish benefit for everyone. PubMed source
Review of clinical trials — Comparison of Coenzyme Q10 (Ubiquinone) and Reduced Coenzyme Q10 (Ubiquinol) (2023): The review compared forms of CoQ10 and summarized cardiovascular research, including studies in people with heart failure. PubMed source
Overview of systematic reviews — Effect of coenzyme Q10 on cardiac function and survival in heart failure (2023): The overview found that existing reviews mainly concern cardiac function and outcomes in heart-failure populations. PubMed source
Systematic review — Coenzyme Q10 Supplementation and Mortality: A Systematic Review and Meta-Analysis (2014): This review found insufficient evidence that CoQ10 supplementation reduces all-cause mortality. PubMed source
Safety: Ask a clinician or pharmacist about interactions, especially if you take warfarin or blood-pressure medicine.
Cardiovascular findings vary by population and formulation; a broad lifespan benefit is not established.
Key evidence
Meta-analysis of randomized trials — Omega-3 Fatty Acids and Cardiovascular Disease: A Updated Meta-Analysis of Randomized Trials (2018): Across 10 randomized trials, this meta-analysis found no significant reduction in coronary heart disease or all-cause mortality. PubMed source
Observational study — The Omega-3 Index: A New Risk Factor for Death from Coronary Heart Disease? (2004): The paper examined an association between blood omega-3 levels and sudden cardiac death risk; an association does not prove supplements prevent deaths. PubMed source
Systematic review and meta-analysis — Association Between Omega-3 Fatty Acid Supplementation and Risk of Major Cardiovascular Disease Events (2012): This review pooled trials of omega-3 supplementation and cardiovascular outcomes, with results that depend on the outcome and study mix. PubMed source
Systematic review and meta-analysis — Effect of omega-3 fatty acids on cardiovascular outcomes (2021): The analysis reported small reductions in some cardiovascular outcomes across trials, not a universal effect across every formulation or population. PubMed source
Safety: Ask your clinician before high-dose use, particularly if you take blood-thinning medicine or have a history of atrial fibrillation.
Dietary associations and blood-pressure trials do not show that supplements extend lifespan in people who are not deficient.
Key evidence
Meta-analysis of prospective cohorts — Dietary Magnesium Intake and the Risk of Metabolic Syndrome: A Meta-Analysis of Prospective Cohort Studies (2016): Higher dietary magnesium intake was associated with lower metabolic-syndrome risk; the observational result does not prove supplements cause the difference. PubMed source
Dose-response meta-analysis of prospective cohorts — Dietary magnesium intake and the risk of cardiovascular disease, type 2 diabetes, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies (2016): This cohort analysis examined dietary magnesium and several health outcomes, including mortality; it cannot establish a supplement effect. PubMed source
Umbrella meta-analysis of randomized trials — Impact of Magnesium Supplementation on Blood Pressure: An Umbrella Meta-Analysis of Randomized Controlled Trials (2024): The review evaluated randomized trials of supplemental magnesium and blood pressure, a risk-factor outcome rather than lifespan. PubMed source
Evidence review — Magnesium Supplementation and Mortality: Insufficient Evidence for Longevity Claims (2012): The review concluded that evidence was insufficient to show magnesium supplements extend lifespan in non-deficient people. PubMed source
Safety: Kidney disease and some medicines affect magnesium safety; ask a pharmacist about spacing it from prescriptions.
Human trials support selected muscle and cognitive outcomes, but have not tested whether creatine extends lifespan.
Key evidence
Systematic review and meta-analysis of randomized trials — Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials (2023): The review found a possible memory benefit in some groups, with evidence varying by age and cognitive measure. PubMed source
Systematic review and meta-analysis — The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis (2024): This review pooled small randomized trials and reported changes in some cognitive tests; it did not measure longevity. PubMed source
Systematic review — Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials (2018): The review evaluated randomized studies of short-term memory and reasoning in healthy adults. PubMed source
Meta-analysis — Effects of creatine supplementation on aging muscle: a meta-analysis (2014): The analysis examined creatine alongside resistance training and muscle outcomes in older adults. PubMed source
Safety: Talk with a clinician before use if you have kidney disease or are being monitored for a medical condition.
Trials in type 2 diabetes report changes in glucose and lipids, while longevity outcomes remain unproven.
Key evidence
Systematic review and meta-analysis of randomized trials — The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (2021): This review pooled randomized trials and found changes in blood-glucose and lipid measures among people with type 2 diabetes. PubMed source
Clinical study — Efficacy of Berberine in Patients with Type 2 Diabetes (2008): The study tested berberine in people with type 2 diabetes and reported lower blood glucose; it was not a longevity trial. PubMed source
Review — Berberine: Gastrointestinal Side Effects and Drug Interactions (2021): The review describes gastrointestinal effects and potential interactions, which are important limits on unsupervised use. PubMed source
Safety: Berberine can interact with diabetes medicines and other drugs; avoid during pregnancy and discuss it with a clinician.
Large trials and reviews do not show a clear general mortality benefit from routine vitamin D supplementation.
Key evidence
Randomized controlled trial — Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease (2019): VITAL found no reduction in cancer incidence or major cardiovascular events from vitamin D in the overall trial population. PubMed source
Systematic review and meta-analysis of randomized trials — Vitamin D Supplementation and Its Impact on Mortality and Cardiovascular Outcomes: Systematic Review and Meta-Analysis of 80 Randomized Clinical Trials (2023): Across 80 randomized trials, the review found no significant reduction in all-cause mortality overall. PubMed source
Systematic review and meta-analysis — Association between Vitamin D Supplementation and Cancer Mortality: A Systematic Review and Meta-Analysis (2022): This review examined cancer mortality across trials; findings for specific cancer outcomes do not establish a general longevity effect. PubMed source
Meta-analysis of randomized trials — Vitamin D Supplementation and Total Mortality: A Meta-analysis of Randomized Controlled Trials (2007): An earlier meta-analysis reported a possible mortality reduction, which later large trials and reviews have not confirmed consistently. PubMed source
Safety: High doses can raise blood calcium; seek clinical guidance with kidney disease, sarcoidosis or thiazide use.
Research covers sleep, skin and animal aging outcomes; human longevity benefits have not been demonstrated.
Key evidence
Randomized controlled trial — The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers (2012): A small study tested glycine before bed and reported improved subjective sleep quality and less fatigue. PubMed source
Systematic review — Oral Collagen Supplementation: A Systematic Review of Clinical Evidence (2019): The review summarized clinical collagen studies, mainly on skin outcomes, and found no evidence for human lifespan extension. PubMed source
Review of mechanisms and animal studies — Glycine and aging: Evidence and mechanisms (2023): This review discusses animal findings and proposed mechanisms; those findings do not demonstrate a longevity effect in people. PubMed source
Systematic review and meta-analysis — Effects of Oral Collagen for Skin Anti-Aging: A Systematic Review and Meta-Analysis (2023): The review pooled trials of collagen and reported improvements in skin hydration and elasticity, not lifespan. PubMed source
Safety: Ask a clinician about glycine if you take clozapine; NAC used in GlyNAC protocols can interact with nitroglycerin.
Aging-related and immune findings are preliminary; human lifespan extension has not been established.
Key evidence
Pilot clinical study — Lactoferrin for the treatment of age-associated inflammation - A pilot study (2021): A pilot study in older adults examined inflammation markers; it was small and did not test lifespan or major clinical outcomes. PubMed source
Systematic review and meta-analysis — Effect of Lactoferrin Supplementation on Inflammation, Immune Function, and Prevention of Respiratory Tract Infections in Humans: A Systematic Review and Meta-analysis (2022): The review synthesized human studies of immune and infection outcomes, which are not direct evidence of longevity. PubMed source
Preclinical animal study — A nutritional supplement containing lactoferrin stimulates the immune system, extends lifespan, and reduces amyloid β peptide toxicity in Caenorhabditis elegans (2017): A nematode study reported lifespan effects in worms; this cannot be assumed to apply to people. PubMed source
Review — The effect of lactoferrin in aging: role and potential (2022): The review discusses proposed aging mechanisms and the limited evidence base, rather than establishing clinical longevity benefits. PubMed source
Safety: Check with a clinician if you have a milk-protein allergy, take medicine or are considering it for a health condition.
Observational findings are inconsistent, and randomized evidence does not establish a general longevity benefit.
Key evidence
Prospective cohort — Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study (2004): This cohort reported an association for combined vitamin C and E supplement use; observational findings cannot establish cause and effect. PubMed source
Meta-analysis of cohort studies — Effect of antioxidant intake patterns on risks of dementia and cognitive decline (2023): The analysis found associations between some antioxidant intake patterns and dementia risk, while combining dietary and supplement data limits causal conclusions. PubMed source
Prospective cohort — Association of vitamin E and C supplement use with cognitive function and dementia in elderly men (2000): This cohort did not find a protective association for Alzheimer's disease from combined supplements, illustrating inconsistent observational results. PubMed source
Randomized controlled trial — Vitamin E, vitamin C, beta carotene, and cognitive function among women with or at risk of cardiovascular disease: The Women's Antioxidant and Cardiovascular Study (2009): The randomized trial found no significant slowing of cognitive decline from antioxidant vitamin supplementation over follow-up. PubMed source
Safety: High-dose vitamin E can affect bleeding risk and supplements can interact with treatment; discuss use with a clinician.
Human trials report changes in NAD-related measures and selected functions, but no human lifespan benefit is demonstrated.
Key evidence
Randomized controlled trial — Ingestion of β-nicotinamide mononucleotide increased blood NAD levels and maintained walking speed in older adults (2024): A small trial in older adults examined blood NAD, walking speed and sleep over 12 weeks; it did not study lifespan.
Review of in vivo evidence — Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence (2018): The review describes animal and mechanistic evidence for NAD precursors, not proof of human longevity effects. PubMed source
Randomized controlled trial — Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners (2021): The trial reported modest aerobic-capacity findings in amateur runners; the clinical significance is uncertain. PubMed source
Randomized controlled trial — The efficacy and safety of β-nicotinamide mononucleotide supplementation in healthy middle-aged adults (2023): A short-term trial examined safety and metabolic markers in middle-aged adults; it did not measure lifespan. PubMed source
Safety: Long-term human safety data are limited; discuss use with a clinician, especially if you have a cancer history.
Small human trials report biomarker or muscle outcomes; no trial has shown that urolithin A extends lifespan.
Key evidence
Randomized controlled trial — Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial (2022): The trial examined muscle endurance and mitochondrial markers in older adults, not lifespan. PubMed source
First-in-human study — The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans (2019): The study assessed tolerability and molecular markers; these are early outcomes, not evidence of longer life. PubMed source
Systematic review — Targeting aging with urolithin A in humans (2024): This review summarized a small set of human studies and found evidence focused on biomarkers and selected functional measures. PubMed source
Randomized controlled trial — Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial (2025): A short trial studied immune-cell measures in adults; the outcome does not establish a lifespan effect. PubMed source
Safety: Long-term outcome data are limited; discuss use with a clinician if you are pregnant, breastfeeding or take medication.
Senolytic findings mainly involve dasatinib plus quercetin; human research is early and does not show longer life.
Key evidence
Animal study — Senolytics improve physical function and increase lifespan in old age (2018): This aged-mouse study tested dasatinib plus quercetin; it does not show that quercetin alone extends human lifespan. PubMed source
Early human pilot study — Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease (2019): A small study in people with diabetic kidney disease examined senescent-cell markers after dasatinib plus quercetin. PubMed source
Phase I randomized trial — Senolytics dasatinib and quercetin in idiopathic pulmonary fibrosis: Phase I RCT on feasibility and tolerability (2023): A small phase I trial focused on feasibility and tolerability of the drug combination, not longevity outcomes. PubMed source
Pharmacokinetic review — Quercetin Bioavailability and Pharmacokinetics: Implications for Efficacy (2003): The review describes absorption and pharmacokinetic questions that complicate translating laboratory findings to oral use. PubMed source
Safety: Quercetin may interact with medicines; ask a clinician or pharmacist before high-dose use or combining it with prescriptions.
Fisetin extended lifespan in a mouse study, but human trials have not demonstrated a longevity benefit.
Key evidence
Animal study — Fisetin is a senotherapeutic that extends health and lifespan (2018): The study reported lifespan and health effects in mice; animal findings do not establish a human benefit. PubMed source
Clinical trial protocol — Senolytics To slOw Progression of Sepsis (STOP-Sepsis) in elderly patients (2024): This paper describes a planned clinical trial; a protocol is not a report of efficacy or safety results. PubMed source
Phase II pilot study — Fisetin for COVID-19: Lessons from a Phase 2 Pilot Study (2023): The pilot did not find a clear clinical benefit versus placebo, underscoring the gap between preclinical and human outcomes. PubMed source
Review — Senolytic drugs: from discovery to translation (2020): The review describes the broader translational challenges and early clinical status of senolytic research. PubMed source
Intervention Testing Program mouse study — Astaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules used (2024): In this genetically diverse mouse study, fisetin did not significantly extend lifespan at the tested doses and schedules, despite earlier positive mouse findings. PubMed source
Safety: High-dose or intermittent senolytic use is not established for people; review medicine interactions with a clinician.
Human research mainly studies skin measures; evidence does not establish an effect on lifespan or aging-related disease.
Key evidence
Randomized controlled trial — Cosmetic benefits of astaxanthin on humans subjects (2012): A small trial in middle-aged women assessed skin hydration, elasticity and wrinkle measures; it did not test longevity. PubMed source
Clinical evidence review — Astaxanthin in Skin Health, Repair, and Disease (2018): The review covers clinical research on skin outcomes and does not establish prevention of disease or longer life. PubMed source
Scope of the cited studies — Scope of the cited studies: The cited astaxanthin studies focus on skin endpoints; they provide no direct human lifespan or mortality result.
Safety: Check with a clinician if you take blood-pressure or blood-thinning medicine, or have a health condition.
Small studies examine blood pressure and cardiovascular markers, but clinical longevity benefit has not been established.
Key evidence
Randomized controlled trial — Effects of nattokinase on blood pressure (2008): A controlled human trial examined blood-pressure changes; it did not assess heart attacks, strokes or lifespan. PubMed source
Clinical study — Effective management of atherosclerosis progress and hyperlipidemia with nattokinase (2022): A multicenter study measured carotid plaque and lipid markers; its design does not establish that nattokinase prevents clinical events. PubMed source
Randomized crossover trial — A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles (2015): A small crossover study measured short-term coagulation markers after one dose, not long-term health outcomes. PubMed source
Randomized controlled trial — Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial (2016): A small North American trial assessed blood pressure and a cardiovascular risk marker over eight weeks. PubMed source
Safety: Nattokinase may affect clotting; do not combine it with anticoagulants or antiplatelet medicines without medical supervision.