Best Longevity Supplements (2026): What Actually Works

The supplement industry will extract $50 billion from consumers this year. Ninety percent of it is garbage dressed in white lab coats and pubmed references that don't say what the marketing claims they say.

You're too smart to buy the hype. You've listened to Huberman and Attia. You know the difference between correlation and causation. You've read enough to know that mouse studies don't translate, that most human trials are underpowered, and that "clinically shown" often means "n=12 in a pilot study funded by the manufacturer."

But you're also too busy to spend 40 hours sorting through 10,000 papers. You have a company to run, decisions to make, and a body that's starting to betray your ambition in ways your doctor dismisses with "everything looks fine" while your energy, recovery, and performance clearly aren't.

This guide uses an evidence-tier system to separate signal from noise in the world of longevity supplements. You'll get specific doses, interaction warnings, and a 90-day starter protocol for building the best longevity supplement stack. No affiliates. No brands. Just the current state of the science for executives who want to optimize lifespan and healthspan without wasting time or money on expensive placebo.

What Are Longevity Supplements?

Longevity supplements are compounds taken to slow biological aging, extend healthspan (years lived in good health), and reduce age-related disease risk. Unlike general wellness supplements, the best longevity supplements target specific aging mechanisms: NAD+ decline, mitochondrial dysfunction, cellular senescence, mTOR dysregulation, and chronic inflammation. The best anti-aging supplements have human clinical trial data, not just mouse studies or mechanistic speculation.

Quick-Reference: Top Longevity Supplements by Evidence Tier

How We Rank Longevity Supplements: The Evidence Tier System

Most supplement articles are written by people with affiliate commissions and biology degrees from Google University. They conflate mouse studies with human data, cite industry-funded research without disclosure, and recommend whatever pays the highest CPM.

Here's the problem: a supplement that extends mouse lifespan by 20% might do nothing in humans. Or worse, it might be actively harmful at the doses people self-prescribe after reading a poorly-interpreted abstract.

The Interventions Testing Program (ITP) has tested 50+ compounds in mice under rigorous conditions. Only 15 extended lifespan. That's a 70% failure rate in an ideal laboratory setting with genetically identical animals eating controlled diets. The translation rate to humans is even worse.

So we need a framework that weighs evidence quality, not just existence.

Evidence Tiers Defined

This system prioritizes safety and evidence quality over novelty and marketing. Tier 1 forms your foundation. Tier 2 gets added once you've optimized T1 and established baseline biomarkers. Tier 3 requires physician supervision. T4 and T5 are generally not worth your money or risk.

Tier 1: Best Longevity Supplements (The Foundation Stack)

These six longevity supplements have the strongest evidence and longest safety records. If you do nothing else, get these right. They form the foundation of any serious longevity supplement stack for anti-aging and healthspan optimization.

Omega-3 (EPA/DHA)

Dose: 2-4g combined EPA/DHA daily

Form: Triglyceride form, EPA-only or EPA-dominant formulations have strongest cardiovascular data

Timing: With largest meal for absorption

Evidence: [T1]

The REDUCE-IT trial (n=8,179) showed 25% relative risk reduction for major cardiovascular events with high-dose EPA (icosapent ethyl 4g daily). This wasn't correction of deficiency, this was pharmacological intervention in statin-treated patients. The effect size rivals many prescription drugs.

Target omega-3 index above 8%. Most people are 4-6%. This requires testing, not guessing.

EPA and DHA modulate inflammatory pathways (reducing arachidonic acid conversion to pro-inflammatory eicosanoids), improve endothelial function, and stabilize cardiac electrical activity. The mechanism is well-understood and the safety profile is excellent across decades of use.

Form matters: Triglyceride form has superior bioavailability versus ethyl ester. Re-esterified triglycerides are the gold standard. Check third-party testing for oxidation (TOTOX score under 26) and heavy metals.

Monitoring: Omega-3 index testing annually. Stop if index above 12% (theoretical bleeding risk, though not demonstrated in trials).

Interactions: Minor additive bleeding risk with anticoagulants. Monitor INR if on warfarin. Generally well-tolerated with other supplements for longevity.

EVOO (Extra Virgin Olive Oil)

Dose: 20-45mL daily as primary dietary fat

Form: High-polyphenol EVOO with at least 5mg/day hydroxytyrosol (EFSA-approved threshold)

Timing: Use for cooking (under 375°F) or as salad dressing

Evidence: [T1]

PREDIMED trial (n=7,447): ~30% cardiovascular risk reduction with Mediterranean diet supplemented with EVOO. Guasch-Ferré et al. 2022 (n=92,383, 28-year follow-up): 19% lower all-cause mortality with EVOO consumption.

This is not "healthy fat" marketing. This is pharmaceutical-grade intervention data rivaling prescription medications.

Oleocanthal (found in EVOO) inhibits COX-1/COX-2 more potently than ibuprofen. Hydroxytyrosol activates Nrf2, SIRT1, and AMPK — the same longevity pathways targeted by expensive supplements. The polyphenol content of quality EVOO delivers anti-inflammatory and mitochondrial benefits that complement your anti-aging supplement stack.

Quality matters: Most supermarket "EVOO" is rancid seed oil. Look for harvest date (within 18 months), dark glass bottles, and third-party polyphenol testing. Expect to pay $15-30 per bottle.

Monitoring: None required. This is food, not supplementation.

Interactions: Synergistic with omega-3. Pairs well with all other longevity supplements in this stack.

Vitamin D3

Dose: 2,000-5,000 IU daily (test-dependent)

Form: D3 (cholecalciferol), not D2

Timing: With fat-containing meal

Evidence: [T1]

The VITAL trial (n=25,871) showed no benefit in vitamin D sufficient individuals. Read that again: supplementation only helps if you're deficient. This is correction of a deficit, not enhancement above normal.

Target serum 25-OH vitamin D: 40-60 ng/mL. Not 20 (deficient), not 100 (potentially toxic).

Most adults are below 30 ng/mL. Sunlight exposure is inconsistent and declines with age. Deficiency is associated with all-cause mortality, but megadosing above sufficiency doesn't provide additional benefit and may increase fall risk in the elderly (likely via muscular weakness from hypercalcemia).

Testing is mandatory. Don't dose blindly. A 25-OH vitamin D test costs $40 and prevents both under- and over-supplementation.

Monitoring: Test baseline, retest at 8 weeks, then annually. Adjust dose to maintain 40-60 ng/mL. If you're below 20, consider 10,000 IU daily for 8 weeks under supervision, then maintenance dosing.

Interactions: Pairs well with K2 (MK-7) if supplementing high-dose D3 long-term (helps direct calcium to bone, not soft tissue). No major interactions with other longevity supplements.

Creatine Monohydrate

Dose: 3-5g daily

Form: Creatine monohydrate (micronized for gastric tolerance)

Timing: Any time, consistency matters more than timing

Evidence: [T1-T2]

Creatine is the most cost-effective supplement in this entire anti-aging supplement guide. Twenty cents per day. Decades of safety data across thousands of athletes, aging adults, and clinical populations.

Marshall et al. (2025) systematic review: cognitive benefits in aging adults. Li et al. (2025): exercise-additive effects on muscle and bone. Mechanism is well-characterized: phosphocreatine buffering maintains ATP availability during high-demand states (cognitive load, physical exertion).

No loading phase needed. Loading (20g × 5 days) saturates stores faster but 3-5g daily achieves the same endpoint in 3-4 weeks.

Creatine may increase intracellular water retention (1-2kg bodyweight increase). This is muscle cell hydration, not bloat. Some individuals are non-responders (already high muscle creatine content, often meat-heavy dieters).

Monitoring: None required. If concerned about kidney function, check creatinine and eGFR at baseline (creatine supplementation raises creatinine slightly without affecting actual kidney function, but establish your baseline).

Interactions: Synergistic with resistance training. Safe with all other supplements for longevity. Avoid combining with nephrotoxic drugs without physician review.

Glycine

Dose: 3-5g daily, evening preferred

Form: Pure glycine powder or as part of GlyNAC protocol (glycine 3g + NAC 600-1,200mg)

Timing: Evening (improves sleep quality)

Evidence: [T1]

ITP-validated lifespan extension in mice (pooled p=0.00004). Kumar et al. 2023 GlyNAC RCT: improved glutathione, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, and physical function — six aging hallmarks improved in just 16 weeks.

Glycine also improves sleep quality at 3g before bed (multiple RCTs). This is rare: a longevity supplement with immediate, subjectively noticeable benefits plus long-term aging mechanism targeting.

Use as GlyNAC protocol for full benefit: Glycine alone works, but combining with NAC (N-acetylcysteine) restores glutathione more effectively. GlyNAC addresses multiple aging hallmarks simultaneously.

Monitoring: None required. Sweet taste makes it easy to add to evening beverage.

Interactions: NAC (standalone) + exercise = blunts hormesis. Use NAC only as part of GlyNAC protocol, not as standalone antioxidant megadose around training. Safe with all other best longevity supplements.

Magnesium (Glycinate or Threonate)

Dose: 200-400mg elemental magnesium

Form: Glycinate for sleep/relaxation, threonate for cognitive emphasis

Timing: Evening (aids sleep)

Evidence: [T1-T2]

Most adults consume insufficient magnesium (under 400mg from diet when RDA is 400-420mg for men). Deficiency is associated with hypertension, insulin resistance, poor sleep quality, and increased all-cause mortality.

Magnesium is a cofactor in more than 300 enzymatic reactions. It regulates calcium channel activity (cardiac rhythm, muscle relaxation), modulates NMDA receptors (neuroprotection), and supports ATP synthesis (every ATP molecule is bound to Mg2+).

Form matters: Oxide has poor bioavailability (~4%). Glycinate is well-absorbed and promotes GABA activity (calming). Threonate crosses the blood-brain barrier more effectively (cognitive/neuroprotective emphasis). Citrate is well-absorbed but can cause loose stools at higher doses (use as a feature if constipated).

Monitoring: Serum magnesium is unreliable (only 1% of total body magnesium is in blood). RBC magnesium is more accurate but rarely tested. Dose based on dietary intake assessment and symptoms (muscle cramps, poor sleep, anxiety often improve with repletion).

Interactions: Take separately from calcium (competitive absorption). Evening dosing avoids interaction with most other anti-aging supplements. Can lower blood pressure additively with antihypertensives.

Tier 2: Advanced Anti-Aging Supplements (The Intermediate Stack)

Add these longevity supplements after your T1 foundation is established and you've obtained baseline biomarkers. These compounds have human RCT data but shorter safety records and higher cost. This is where your longevity supplement stack moves beyond deficiency correction into optimization territory.

NMN/NR (NAD+ Precursors)

Dose: NMN 250mg or NR 300mg daily (studied doses)

Form: Stabilized NMN or NR (nicotinamide riboside)

Timing: Morning (NAMPT circadian peak)

Evidence: [T2]

NAD+ declines 50% between age 40 and 60. NAD+ is required for sirtuin (SIRT1-7) activity, PARP1 DNA repair, and mitochondrial function. Restoring NAD+ is mechanistically compelling for any anti-aging supplement regimen.

Morifuji et al. (2024): NMN 250mg increased blood NAD+ and improved functional outcomes in older adults. The effect size was modest but significant. NR has similar data from earlier trials.

Critical update: NMN FDA-confirmed legal supplement (September 2025). The regulatory uncertainty is resolved.

Important caveat: NMN benefits in meta-analyses show reliable NAD+ elevation but NO significant functional benefit versus placebo in most endpoints. This is NAD supplement reality: the biomarker moves, but translating that to performance, recovery, or longevity markers is less certain.

NMN → NMN → NAD+ via NMNAT. NR → NMN → NAD+ via NRK. Both pathways work. NMN may bypass the NRK bottleneck but requires stabilization (NMN degrades in water). NR is more stable but adds a conversion step.

Pair with TMG (trimethylglycine, 500mg): NAD+ synthesis consumes methyl groups. TMG acts as a methyl donor, preventing homocysteine elevation from chronic NAD+ precursor use.

DO NOT waste money on NAD+ IV infusions. $1,000+ per session. Expert consensus (Paulvin): "We just don't know if there's any benefit." Oral NMN at $40/month achieves measurable NAD+ increase. The IV costs 25x more with T4-T5 evidence.

Monitoring: Homocysteine (quarterly if using high-dose NAD supplement without TMG), otherwise none required. Some users report sleep disruption if dosed in evening.

Interactions: Separate from metformin by 6+ hours (metformin is a weak Complex I inhibitor, which theoretically opposes NAD+ elevation's benefit). No issues with other T1-T2 compounds.

Urolithin A

Dose: 500-1,000mg daily

Form: Direct supplementation (dietary conversion from ellagitannins is inefficient)

Timing: Morning or pre-workout

Evidence: [T2]

Urolithin A activates mitophagy (selective autophagy of damaged mitochondria) via PINK1/Parkin pathway. This is a non-overlapping mechanism with NAD supplement precursors, making it complementary rather than redundant in your longevity supplement stack.

Denk et al. (2025) RCT: improved muscle endurance and mitochondrial function. Mallet et al. (2025): anxiety reduction and mitochondrial rescue in stress models. The human data is recent but growing.

Dietary sources (pomegranate, walnuts, berries) provide ellagitannins, which gut bacteria convert to urolithin A. Problem: only 40% of people have the right microbiome composition for efficient conversion. Direct supplementation bypasses this variability.

Monitoring: None required. Watch for GI upset (rare, usually dose-dependent).

Interactions: Synergistic with exercise (amplifies mitochondrial adaptation). No contraindications with other stack compounds.

Astaxanthin

Dose: 8-12mg daily with fat

Form: Natural astaxanthin from Haematococcus pluvialis

Timing: With largest meal (fat-soluble)

Evidence: [T2]

ITP-validated: 12% lifespan extension in male mice (replicated at all three ITP sites). 6,000x more potent antioxidant than vitamin C in vitro. Unlike beta-carotene, astaxanthin shows no pro-oxidant risk even at high doses.

Multiple RCTs show reduced LDL oxidation, improved skin elasticity, and reduced exercise-induced muscle damage. The antioxidant mechanism is well-characterized: quenches singlet oxygen and peroxyl radicals more effectively than other carotenoids.

Why this belongs in Tier 2: ITP validation gives astaxanthin stronger animal longevity data than most "anti-aging supplements" marketed at 10x the price. At $20/month, it's a high-value addition to the best longevity supplement stack.

Monitoring: None required.

Interactions: Fat-soluble, so take with omega-3 for enhanced absorption. Safe with all other longevity supplements.

CoQ10/Ubiquinol

Dose: 200-300mg daily

Form: Ubiquinol (reduced form, better absorption in older adults)

Timing: With fat-containing meal

Evidence: [T2]

Q-SYMBIO trial (n=420, 2 years): 50% reduction in major adverse cardiac events, 43% lower cardiovascular mortality with CoQ10 supplementation in heart failure patients. KiSEL-10 trial: 53% lower CV mortality persisting at 12-year follow-up.

Mandatory if on statins: Statins deplete CoQ10 by inhibiting the same mevalonate pathway. Statin-induced myopathy correlates with CoQ10 deficiency. If you're on statins, this moves from T2 to T1.

Ubiquinol is the reduced (active) form of CoQ10. Conversion of ubiquinone to ubiquinol declines with age, making ubiquinol the preferred form for anti-aging supplement protocols in people over 40.

Monitoring: None required unless on statins (monitor CK and liver enzymes regardless).

Interactions: Berberine + CoQ10 = CYP3A4 interaction, monitor if combining. Safe with other longevity supplements.

Melatonin

Dose: 0.3-1mg before bed (physiologic dose, not pharmacologic)

Form: Immediate-release or sustained-release based on sleep pattern

Timing: 30-60 minutes before bed

Evidence: [T2]

Pineal melatonin production declines 10-fold from adolescence to old age. This is genuine age-related deficiency, not just "sleep supplement" marketing.

Melatonin concentrates in mitochondria at concentrations 100x higher than blood levels. It scavenges ROS, upregulates SIRT1, SIRT3, and PGC-1α (mitochondrial biogenesis). The anti-aging mechanism extends far beyond sleep improvement.

Dose matters: Most melatonin supplements are 3-10mg (pharmacologic doses causing next-day grogginess). Physiologic replacement is 0.3-1mg. Higher doses don't improve sleep quality and may desensitize receptors.

Monitoring: None required. Adjust dose based on sleep quality and morning grogginess.

Interactions: May enhance effects of sedatives. Safe with all other supplements for longevity. Take 6+ hours after caffeine for maximum effectiveness.

Lutein/Zeaxanthin

Dose: 10mg lutein + 2mg zeaxanthin daily

Form: From marigold extract

Timing: With fat-containing meal

Evidence: [T2]

AREDS2 (n=4,203, Tier 1 evidence): macular degeneration prevention. These are the only carotenoids that accumulate in both retina AND brain tissue.

Hammond 2017: cognitive improvements after 1 year of lutein/zeaxanthin supplementation. The brain deposition is why this belongs in a longevity supplement stack, not just eye health protocols.

Why this matters for executives: Macular degeneration is the leading cause of vision loss over 50. Cognitive decline correlates with macular pigment optical density. This is preventive medicine with dual benefits.

Monitoring: None required.

Interactions: Fat-soluble, take with omega-3 or EVOO. Safe with all other anti-aging supplements.

Spermidine

Dose: 1-6mg daily

Form: Wheat germ extract or synthetic

Timing: Morning

Evidence: [T2-T3]

Spermidine induces autophagy via AMPK activation and EP300 inhibition. This is cellular housekeeping, clearing damaged proteins and organelles — a core longevity mechanism.

Epidemiological data: higher dietary spermidine intake correlates with reduced all-cause mortality. Interventional human data is limited but promising. The mechanism is well-characterized in model organisms.

Dietary sources: wheat germ (highest concentration), aged cheese, mushrooms, soybeans. Most Western diets provide 5-10mg daily. Supplementation adds insurance.

Monitoring: None required.

Interactions: Mechanistically complementary with urolithin A (both promote autophagy via different pathways). No contraindications with other best longevity supplements.

Curcumin (Liposomal or Phytosomal)

Dose: 500-1,000mg curcuminoids

Form: Liposomal, phytosomal (Meriva), or piperine-enhanced

Timing: With food

Evidence: [T2]

Curcumin modulates NF-κB (master inflammatory regulator), activates Nrf2 (antioxidant response), and has been studied in everything from arthritis to Alzheimer's.

The problem is bioavailability. Plain curcumin has ~1% oral bioavailability. Don't buy cheap turmeric powder and expect systemic effects.

Liposomal formulations achieve 8-10x higher bioavailability. Phytosomal (Meriva) uses phosphatidylcholine binding. Piperine (black pepper extract) inhibits curcumin metabolism but has drug interaction concerns.

Monitoring: Liver enzymes if using high-dose long-term (rare hepatotoxicity case reports, causality unclear).

Interactions: CYP3A4 substrate, may interact with statins, anticoagulants. Use caution if on multiple medications. This is one area where a NAD supplement has fewer interaction concerns.

Sulforaphane

Dose: 10-30mg or 1-2 servings broccoli sprouts

Form: Stabilized sulforaphane or fresh sprouts

Timing: Morning

Evidence: [T2]

Sulforaphane activates Nrf2, the master regulator of phase 2 detoxification enzymes. This enhances cellular defense against oxidative stress and xenobiotics — relevant for longevity supplement protocols targeting inflammation.

Broccoli sprouts have 10-100x more glucoraphanin (sulforaphane precursor) than mature broccoli. Myrosinase enzyme (present in raw sprouts, destroyed by cooking) converts glucoraphanin to active sulforaphane.

Supplements work but fresh sprouts are cheaper and more reliable if you'll eat them consistently.

Monitoring: None required.

Interactions: May enhance phase 1 and phase 2 detoxification, potentially affecting drug metabolism. Generally safe but consult physician if on critical-dose medications.

Tier 3: Physician-Supervised Longevity Supplements

Rapamycin

Dose: 2-6mg weekly (pulsed protocol)

Evidence: [T2-T3]

Status: Prescription only

Rapamycin inhibits mTORC1, mimicking some benefits of caloric restriction without the caloric restriction. ITP meta-analysis: 167 animal studies showing consistent lifespan extension. Now 15 ITP-validated molecules (not 12 as previously reported).

But here's the uncomfortable truth: Hands et al. (2025) human review states "limited evidence for longevity benefits in healthy adults." The animal data is strong. The human translation is speculative.

PEARL trial update: Compounded rapamycin has approximately one-third bioavailability of commercial sirolimus. Dosing from compounding pharmacies requires adjustment or therapeutic drug monitoring.

Bryan Johnson (Blueprint protocol, $2M/year spent on longevity) discontinued rapamycin due to glucose dysregulation. Real-world N-of-1 data matters when RCT evidence is sparse.

Side effects:

• Elevated LDL and triglycerides (dose-dependent)
• Mouth sores (aphthous ulcers)
• Glucose dysregulation (mTOR regulates insulin signaling)
• Immunosuppression (it's a transplant anti-rejection drug)

Monitoring (mandatory):

• Fasting glucose and HbA1c quarterly
• Lipid panel quarterly
• CBC quarterly (watch for cytopenias)
• Oral exam (mouth sores are common)

Interactions:

• Do not combine with GH secretagogues (mechanistic antagonism, see Watch List)
• Separate from resistance training by 24h (mTORC1 drives muscle protein synthesis)
• CYP3A4 substrate (grapefruit, statins, many drugs interact)

Who should consider: Individuals with family history of cancer (mTOR inhibition has anti-cancer properties) and willingness to accept metabolic trade-offs under close physician supervision.

Who should avoid: Anyone with active infection risk, uncontrolled diabetes, or poor medication adherence.

Metformin

Dose: 500-1,000mg daily (extended release)

Evidence: [T1 animal NEGATIVE, T3 human pending]

Status: Prescription only (off-label for longevity)

Metformin activates AMPK, mimicking energy scarcity. It's the most-prescribed diabetes drug globally with 60+ years of safety data.

Here's what the longevity community got wrong: meta-analysis of vertebrate studies shows metformin does NOT extend lifespan in non-diabetic animals. Read that again. The foundational assumption is questionable.

Critical correction: The TAME trial (Targeting Aging with Metformin) has NEVER enrolled patients. It's been "forthcoming" for years. Do not cite TAME as evidence. We don't have the answer yet.

Use case: If you're insulin resistant (HOMA-IR above 2.5), metformin is appropriate therapy. If you're metabolically healthy, the risk-benefit is unclear.

Side effects:

• GI distress (dose-dependent, ER formulation helps)
• Vitamin B12 deficiency (long-term use, supplement B12)
• Lactic acidosis (rare but serious, avoid if eGFR is below 30)

Critical interaction: MASTERS trial showed metformin blunts exercise adaptations (strength and VO2max gains). If you train hard, this is a deal-breaker. Avoid on training days or skip metformin entirely.

Monitoring:

• Fasting glucose, insulin, HbA1c quarterly
• Vitamin B12 annually
• Kidney function annually

Interactions:

• Separate from NMN by 6+ hours (Complex I inhibition may oppose NAD supplement benefits)
• Do not take on exercise days (blunts adaptations)
• Contraindicated with iodinated contrast (lactic acidosis risk)

Berberine

Dose: 500mg 2-3x daily with meals

Evidence: [T2]

Status: OTC supplement

Berberine activates AMPK similarly to metformin but via a different pathway. It improves glucose metabolism and lipid profiles in metabolic syndrome patients.

Critical warning: Berberine is a potent CYP3A4 inhibitor. This is the enzyme that metabolizes statins. Combining berberine with atorvastatin or simvastatin increases statin blood levels, raising myopathy and rhabdomyolysis risk.

Monitoring:

• Liver enzymes (AST, ALT) at baseline and quarterly
• Lipid panel quarterly
• Do NOT combine with statins without physician approval and dose adjustment

Interactions:

• CYP3A4 substrates (many drugs)
• Avoid with immunosuppressants, anticoagulants without physician review
• Berberine + CoQ10 = CYP3A4 interaction, monitor

Fisetin

Dose: 500mg × 2-3 consecutive days monthly (pulsed senolytic protocol)

Evidence: [T3]

Status: OTC supplement

Fisetin induces apoptosis in senescent cells (cells that stopped dividing but secrete inflammatory factors). Senescent cell burden increases with age and drives tissue dysfunction.

Mechanism: BCL-xL inhibition (pro-survival protein in senescent cells).

The problem: all human data is preliminary. Animal studies show promise but we lack large-scale human RCTs. The pulsed protocol mimics Kirkland's research but human translation is speculative.

Monitoring: None established. Theoretical concern for apoptosis in healthy cells at high doses.

Interactions: Avoid with anticoagulants during pulse days (senolytics may increase bleeding risk).

Watch List: Anti-Aging Supplements Awaiting Better Evidence

Repair Peptides (BPC-157, TB-500)

Evidence: [T3-T4]

Status: Experimental, physician-supervised

BPC-157 (Body Protection Compound) has compelling preclinical data for tissue repair, gut healing, and injury recovery. TB-500 (Thymosin Beta-4) shows similar promise for wound healing and inflammation reduction. Practitioners working with these peptides report meaningful clinical outcomes, particularly for joint injuries, tendon repair, and GI conditions.

The limitation: large-scale human RCTs don't exist yet. Atria Institute (Peter Attia's research organization) notes "no high-quality, long-term human studies demonstrating improved healthspan or survival." That's fair — but absence of evidence is not evidence of absence. These compounds are earlier in their evidence journey, not debunked.

Key consideration: Source quality matters enormously. Work with a physician who uses reputable compounding pharmacies with third-party testing. Purity and dosing consistency vary wildly across suppliers.

Bottom line: Worth discussing with a knowledgeable longevity physician if you have a specific therapeutic target (injury recovery, gut repair). Not yet justified as a general longevity supplement for everyone.

GH Secretagogues (Ipamorelin, Sermorelin, CJC-1295)

Evidence: [T4]

Status: Context-dependent — longevity trade-offs

Growth hormone secretagogues are popular in the anti-aging clinic circuit, and they deliver real short-term results: improved body composition, better recovery, enhanced sleep quality. The appeal is obvious.

The longevity concern is mechanistic: GH → IGF-1 → PI3K-AKT → mTORC1 activation. This is the opposite direction of rapamycin and caloric restriction, both of which extend lifespan in animal models. Ames dwarf mice (GH deficient) live 50% longer. Humans with Laron syndrome (GH receptor mutations) have dramatically reduced cancer rates.

This doesn't mean GH secretagogues are harmful in all contexts. Short-term use for specific goals (sarcopenia recovery, post-surgical healing) may be reasonable. But chronic use for longevity purposes conflicts with the mTOR inhibition strategy that most current evidence favors.

Cost: $300-500/month from compounding pharmacies.

Bottom line: May have a role for specific, time-limited therapeutic goals. Contraindicated as a long-term longevity strategy, especially if you're pursuing mTOR-targeting interventions like rapamycin.

NAD+ IV Infusions

Evidence: [T4]

Status: Unproven premium over oral alternatives

IV wellness clinics charge $1,000+ per session to drip NAD+ directly into your bloodstream. The pitch sounds compelling: bypass digestion, get NAD+ directly to cells.

The reality: expert consensus is "we don't know if there's any benefit" over oral alternatives (Paulvin, cited by longevity physicians). There are no comparative RCTs of NAD+ IV versus oral NMN. Oral NMN at $40/month produces measurable NAD+ elevation.

Some practitioners report patients feel better acutely after IV NAD+ (likely a combination of hydration, placebo, and acute NAD+ spike). Whether this translates to meaningful long-term benefit over consistent oral NAD supplement use is unknown.

Bottom line: If you're already taking oral NMN and want to experiment, one or two sessions may satisfy your curiosity. As a regular protocol, the cost-benefit ratio doesn't justify it until comparative data exists. Save the money for your best longevity supplements with proven RCT data.

Resveratrol

Evidence: [T3-T4]

Status: Bioavailability challenge

Resveratrol was popularized by David Sinclair's research on sirtuin activation. The mechanism is interesting. The human data has been mixed.

Oral bioavailability is ~10%. Most resveratrol is metabolized before reaching systemic circulation. High-dose studies (1-2g) show some metabolic benefits but the effect sizes are modest compared to other compounds in this article.

Pterostilbene (a methylated analog) has better bioavailability and may be the more practical choice if you're interested in this pathway. But even then, the evidence for longevity-specific outcomes is limited compared to T1-T2 compounds.

Bottom line: Not a priority. If budget and pill count allow after establishing your T1-T2 foundation, pterostilbene is the more rational version of this bet.

Longevity Supplement Stack Interactions

Longevity supplement stacks are not just additive, they're interactive. Some combinations are synergistic. Some are antagonistic. Some are dangerous.

Key principles:

• Don't oppose mechanisms (rapamycin + GH is irrational)
• Separate competing pathways by timing
• Monitor for additive risks (bleeding, drug interactions)
• Start one compound at a time (isolate variables)

The 90-Day Longevity Supplement Protocol

Phased implementation reduces variables, establishes baseline, and builds sustainable habits.

Phase 1: Foundation (Weeks 1-4)

Goal: Establish T1 baseline, get labs, build daily routine.

Morning:

• Omega-3: 2g EPA/DHA with breakfast
• EVOO: 20-45mL as primary dietary fat
• Vitamin D3: 2,000-5,000 IU with breakfast (test-dependent)
• Creatine: 5g (with or without food)

Evening:

• Magnesium glycinate: 200-400mg with dinner
• Glycine: 3-5g before bed

Labs (Week 0):

• 25-OH Vitamin D
• Omega-3 index
• Fasting glucose, insulin (calculate HOMA-IR)
• Lipid panel (LDL, HDL, TG, ApoB if available)
• Creatinine, eGFR
• CBC
• hsCRP
• Liver enzymes (AST, ALT)

Cost: ~$75/month for supplements + $150-300 for labs (one-time baseline)

Assess: Energy, sleep quality, recovery. Most people notice improved sleep (magnesium + glycine) and stable energy within 2-3 weeks.

Phase 2: Intermediate (Weeks 5-8)

Goal: Add T2 compounds, monitor response, optimize dosing.

Add to morning routine:

• NMN: 250mg
• TMG: 500mg
• Urolithin A: 500mg
• Spermidine: 1-3mg
• Astaxanthin: 8-12mg
• CoQ10/Ubiquinol: 200-300mg
• Lutein/Zeaxanthin: 10mg/2mg

Add to evening routine:

• Melatonin: 0.3-1mg before bed

Continue T1 foundation unchanged.

Cost: ~$175/month total

Assess: Note any changes in energy, cognitive clarity, workout recovery. If no sleep disruption, you've confirmed NMN timing works for you.

Phase 3: Advanced (Weeks 9-12, optional)

Goal: Consider T3 interventions if risk-benefit supports it.

Physician consult required. Discuss:

• Rapamycin (if family history of cancer, willing to accept metabolic trade-offs)
• Metformin (if HOMA-IR above 2.5, insulin resistant)
• Berberine (alternative to metformin, requires CYP3A4 interaction review)

Labs (Week 12):

• Repeat all baseline labs
• Compare markers (lipids, glucose, inflammation)
• Adjust doses based on response

Cost: ~$200-250/month (if adding T3 compounds)

Assess: Review quarterly. Longevity is a long game, not a 90-day sprint.

Daily Timing Schedule (Consolidated)

Morning (with breakfast):

• Omega-3, EVOO, Vitamin D3, NMN, TMG, Urolithin A, Spermidine, Creatine, Astaxanthin, CoQ10, Lutein/Zeaxanthin

Evening (with dinner):

• Magnesium, Glycine (before bed), Melatonin (30-60 min before bed)

Weekly (if prescribed):

• Rapamycin (pulsed, typically Monday morning)

Simplicity wins. Twice-daily dosing is sustainable. Eighteen-pill-a-day protocols fail due to adherence.

Biomarker Testing for Your Longevity Supplement Stack

Taking longevity supplements without monitoring is hope, not strategy. Test quarterly. Adjust based on data.

Essential Bloodwork

Red Flags to Watch

• Rising fasting glucose or insulin (pre-diabetes)
• Elevated liver enzymes (supplement toxicity, fatty liver)
• Declining eGFR (kidney dysfunction)
• Persistent elevated hsCRP (chronic inflammation)
• Homocysteine above 15 (cardiovascular risk, B-vitamin deficiency)

Quarterly review cycle keeps you ahead of problems. Annual physicals catch problems. Quarterly monitoring optimizes.

Longevity Supplements FAQ

What's the single best supplement for longevity?

There isn't one. If forced to choose: omega-3. Strongest human data, clearest mechanism, best risk-reward ratio. But the real answer is test your vitamin D, optimize if deficient, get sufficient omega-3, add EVOO as your primary fat, and lift heavy weights. Supplements for longevity augment fundamentals, they don't replace them.

Is rapamycin safe for healthy people?

Unknown. Animal data is strong. Human data is limited. Hands et al. (2025): "limited evidence for longevity benefits in healthy adults." Side effects (glucose dysregulation, immunosuppression, lipid changes) are real. This is not a lifestyle supplement, it's a pharmaceutical intervention with unknown long-term risk in healthy individuals. Physician supervision is mandatory. Many experts are waiting for better human data before recommending it broadly.

NMN vs NR: which is better?

Both raise NAD+. NMN may bypass the NRK1 bottleneck but requires stabilization. NR is more stable but adds a conversion step. Studied doses: NMN 250mg, NR 300mg. Human data exists for both. Pick one, use it consistently, pair with TMG. Don't overthink it. Both are valid NAD supplement options.

How much does a longevity protocol cost?

Phase 1 (T1 foundation): $75/month. Phase 2 (T1 + T2): $175/month. Phase 3 (adding T3): $200-250/month. Labs add $150-300 quarterly. Total annual cost: $2,500-4,000 including monitoring. Compare to one ER visit ($5,000+) or chronic disease management ($10,000+/year). Prevention is cheaper than treatment.

When do I add advanced compounds?

After 6-12 months on T1-T2 foundation with quarterly labs showing stable optimization. Don't jump to rapamycin because a podcast made it sound interesting. Build the foundation, establish monitoring discipline, then consider T3 interventions with physician supervision if your risk profile and goals support it.

What about EVOO for longevity?

EVOO is now Tier 1 based on PREDIMED trial (n=7,447, ~30% CV risk reduction) and JACC 2022 study (n=92,383, 28 years, 19% lower all-cause mortality). Oleocanthal and hydroxytyrosol in high-quality EVOO activate longevity pathways (Nrf2, SIRT1, AMPK) comparable to expensive supplements. Use 20-45mL daily as your primary dietary fat. This is food-based longevity optimization, not supplementation.

The Bottom Line on Longevity Supplements

The uncomfortable truth most supplement articles won't tell you: exercise has stronger longevity evidence than any supplement. Sleep quality matters more than NMN. Maintaining lean mass after 40 predicts survival better than your NAD+ levels.

Longevity supplements are supplements. They augment a strong foundation, they don't replace it. No amount of rapamycin compensates for sedentary lifestyle and sleep deprivation.

But if you've handled the fundamentals, if you're training consistently, sleeping 7-8 hours, managing stress, and eating to support performance, then the best longevity supplements in this evidence-tiered stack represent the current frontier of extending healthspan and lifespan.

Start with T1. Get labs. Build the habit. Add T2 after the foundation is solid. Consider T3 only with physician supervision and clear rationale.

Test quarterly. Adjust based on data. Commit to the long game.

The best longevity supplement stack is a 40-year optimization problem, not a 90-day quick fix. Consistency and evidence-based decision-making beat novelty and hype every time.