Compound Deep-Dives

GlyNAC (Glycine + NAC)

Flagship glutathione restoration — human RCT backbone

Dual-precursor strategy rebuilding the glutathione triad (GSH, cysteine, glycine). Tier A human data for oxidative stres…

NMN (Nicotinamide Mononucleotide)

NAD+ precursor — sirtuin and PARP fuel

Direct NAD+ precursor bypassing NAMPT rate-limiting step. Restores NAD+ pools that decline ~50% between ages 40–60, acti…

NR (Nicotinamide Riboside)

NAD+ precursor alternative — human RCT data, manual stack substitution

Legitimate NAD+ precursor with human trial footprint. TNiC defaults to NMN for stack integration; this module covers whe…

Rapamycin (Sirolimus)

mTORC1 inhibition — strongest preclinical lifespan drug

Educational deep-dive on the most replicated lifespan-extending pharmacological intervention. Prescription-only; immunos…

TUDCA (Tauroursodeoxycholic Acid)

ER stress chaperone — proteostasis & mitochondrial support

Bile acid derivative stabilizing protein folding, reducing ER stress, and supporting mitochondrial membrane integrity. S…

Grape Seed Extract (95% OPC)

A potent OPC antioxidant with real human RCTs behind its blood-pressure and vascular support

Grape Seed Extract standardized to ≥95% OPC (oligomeric proanthocyanidins) is one of the better-studied polyphenol antio…

Sulforaphane

NRF2 master regulator — 200+ cytoprotective genes

Isothiocyanate from broccoli sprouts that covalently modifies KEAP1, releasing NRF2 to drive phase-II detox, proteasome …

R-Alpha Lipoic Acid (R-ALA)

Mitochondrial redox recycler — NRF2 stack completion

Recycles oxidized glutathione, vitamins C and E. Cofactor for pyruvate dehydrogenase in mitochondria. Completes the NRF2…

Ca-AKG (Calcium Alpha-Ketoglutarate)

Epigenetic cofactor & TCA fuel — highest hallmark breadth per gram

TCA cycle intermediate and obligate cofactor for TET, JMJ, and PHD enzymes that reverse age-related DNA and histone meth…

Trans-Resveratrol

SIRT1 activator — caloric restriction mimetic

Phytoalexin activating SIRT1 and AMPK. Synergistic with NAD+ precursors for epigenetic and mitochondrial remodeling. Tie…

Taurine

Age-depleted osmolyte — Science 2023 lifespan signals

Sulfonic amino acid buffering mitochondrial stress and declining ~80% with age. Tier B: strong Singh 2023 Science mechan…

Spermidine

Autophagy polyamine — Madeo 2021 memory RCT

Dietary and supplemental polyamine inducing autophagy via EP300 inhibition. Tier B: human pilot memory outcomes; strong …

Pterostilbene

Methylated resveratrol — 4× bioavailability

Stilbenoid SIRT1 activator with superior human PK vs trans-resveratrol. Tier B: Kapetanovic 2011 safety/PK; compare with…

Berberine HCl

AMPK activator — metformin-equivalent glucose outcomes without a prescription

Isoquinoline alkaloid activating AMPK with RCT-equivalent glucose control vs metformin (500 mg TID, 13-week head-to-head…

Urolithin A

Mitophagy activator — Phase 2 muscle trial, Tier A

Gut-derived metabolite from ellagitannin polyphenols that activates mitophagy — the selective clearance of damaged mitoc…

Fisetin

Senolytic flavonoid — Mayo Clinic pilot, highest potency ranking

Flavonoid with the highest senolytic potency of dietary compounds tested (Kirkland lab, 2018). Mayo Clinic pilot RCT red…

CoQ10 (Ubiquinol)

Electron transport chain cofactor — essential for statin users

Mitochondrial cofactor required at Complex I, II, and III of the electron transport chain. Declines ~50% by age 70. Ubiq…

Omega-3 (EPA + DHA)

REDUCE-IT: 25% CV event reduction — SPM resolution axis

EPA and DHA serve as precursors to specialized pro-resolving mediators (SPMs) — resolvins and protectins — that actively…

Cocoa Flavanols

Among the best-studied nutrients for the aging vascular system — NO, blood pressure, and a cardiovascular-death signal in COSMOS

Cocoa flavanols (chiefly epicatechin) raise nitric-oxide availability, improve flow-mediated dilation, and lower blood p…

Citrus Bergamot

A polyphenol lipid lever with real RCTs lowering LDL and triglycerides — statin-like pathway, no prescription

Citrus bergamot concentrates flavonoids that behave like natural HMG-CoA reductase modulators and activate AMPK. Human R…

L-Theanine

Calm, focused alertness without sedation — the most replicable acute nootropic, and it tames caffeine jitter

The amino acid in green tea that produces alert-but-relaxed focus. Human EEG studies show increased alpha-wave activity …

Collagen Peptides

One of the best-evidenced supplements for skin elasticity, joint comfort, and bone — building blocks that also signal repair

Hydrolyzed collagen delivers bioactive di- and tri-peptides that reach skin, joints, and bone and instruct fibroblasts a…

Beetroot / Dietary Nitrate

A direct, food-based nitric-oxide boost — lower blood pressure and more efficient muscles, backed by consistent RCTs

Dietary nitrate converts to nitric oxide through a route independent of the age-impaired eNOS enzyme — a back-up NO supp…

Lion's Mane

A mushroom that stimulates nerve growth factor — a compelling, low-risk cognition and mood play

Lion's mane hericenones and erinacines stimulate NGF and BDNF, the signals that keep neurons healthy and connected. A do…

Citicoline (CDP-Choline)

Highly bioavailable choline for attention and memory — feeds both acetylcholine and neuronal membrane repair

Citicoline supplies the raw material for acetylcholine (attention, memory) and phosphatidylcholine (neuronal membranes).…

Nattokinase

A fibrinolytic enzyme from natto with human RCTs for blood pressure, clot breakdown, and arterial health

Nattokinase, the enzyme from fermented soy (natto), directly degrades fibrin and supports healthy clotting balance and b…

MitoQ (Mitoquinol)

CoQ10 re-engineered to reach inside mitochondria — a landmark RCT restored older adults' vascular function

A lipophilic cation concentrates ubiquinol several-hundred-fold inside mitochondria, quenching oxidative stress at its s…

Aged Garlic Extract

One of the best-evidenced cardiovascular supplements — lowers blood pressure and slows coronary plaque in imaging trials

Aging converts harsh allicin into stable, bioavailable S-allylcysteine, delivering reliable cardiovascular benefit witho…

Metformin

Prescription biguanide with Tier-A diabetes data and a genuinely unsettled Tier-B geroprotection case.

Metformin inhibits mitochondrial Complex I and activates AMPK, with strong human evidence for glucose control and diabet…

Creatine Monohydrate

Phosphocreatine ATP buffer — Tier A for muscle and strength in aging

The best-evidenced legal amplifier of resistance training for defending against sarcopenia, with a large older-adult RCT…

Vitamin D3 (Cholecalciferol)

Fixing a real vitamin-D deficiency is one of the highest-yield, best-evidenced moves in the stack

Vitamin D3 (cholecalciferol) is a nuclear-hormone precursor acting on hundreds of genes across bone, immune, and muscle …

Magnesium (Glycinate / Threonate)

Essential ATP-Mg2+ cofactor — modest, repletion-shaped RCT wins for BP, insulin sensitivity, and sleep

Cofactor for 300+ enzymes including ATP-Mg2+, DNA repair, and insulin signaling; deficiency is common. Tier B: real meta…

Curcumin (Curcuminoids)

Turmeric polyphenol with Tier-A knee-OA symptom relief, Tier-B systemic inflammation effects, and a defining bioavailability problem

Curcumin suppresses NF-κB and activates Nrf2, with strong human RCT evidence for knee-osteoarthritis pain (as effective …

Quercetin

Founding senolytic flavonoid — strong mechanism, early human outcomes

The 'Q' in the dasatinib + quercetin senolytic protocol. Well-established preclinically with promising but small, mostly…

Glucosamine Sulfate

Large observational cohorts link regular use to lower mortality — associational, not causal.

An aminosaccharide joint supplement with a striking but confounded UK Biobank association to lower cardiovascular and al…

Vitamin K2 (MK-7)

The calcium-routing cofactor: activates MGP and osteocalcin, with mixed 3-year RCT outcomes

MK-7 is the vitamin K2 form that carboxylates matrix Gla protein and osteocalcin, steering calcium away from arteries an…

Melatonin

Circadian hormone and mitochondrial antioxidant — Tier A for sleep, Tier B/C for longevity.

Pineal indoleamine that sets circadian timing and doubles as a mitochondria-concentrated antioxidant; secretion declines…

Glycine

Conditionally-essential amino acid: glutathione substrate, methyl-group buffer, and NMDA-mediated sleep aid — small but real human RCTs, preclinical lifespan signal.

Glycine is the third glutathione residue and a co-limiting substrate with cysteine in aging. Small human RCTs support 3 …

N-Acetylcysteine (NAC)

Cysteine donor that refills glutathione — strong mechanism and safety, thin standalone longevity data (Tier B).

NAC is a plasma-stable cysteine precursor that raises glutathione, with decades of approved mucolytic and acetaminophen-…

Zinc

Essential trace mineral; corrects age-related immune decline in the deficient, with genuine RCT infection data and indirect longevity rationale.

Zinc is a cofactor for ~300 enzymes including antioxidant SOD and thymulin; deficiency is common in older adults and mir…

L-Citrulline

Nitric-oxide support — evidence-graded deep dive

Oral citrulline raises arginine availability and supports nitric-oxide signaling; human evidence focuses on vascular fun…

EGCG (Green Tea Catechin)

AMPK and redox signaling — evidence-graded deep dive

Green-tea catechins influence AMPK and inflammatory signaling, but isolated high-dose extracts can injure the liver and …

Astaxanthin

Membrane antioxidant defense — evidence-graded deep dive

This lipid-soluble carotenoid spans cell membranes and has human studies in skin, oxidative stress, and exercise; direct…

Apigenin

CD38 and inflammatory signaling — evidence-graded deep dive

Apigenin inhibits CD38 and inflammatory pathways in laboratory models, but oral human intervention evidence is sparse an…

Luteolin

Neuroinflammatory signaling — evidence-graded deep dive

Luteolin is a preclinical anti-inflammatory and senotherapeutic candidate; available human work uses small studies or co…

Ergothioneine

OCTN1 cytoprotective transport — evidence-graded deep dive

This diet-derived thiol has a dedicated transporter and strong observational or mechanistic rationale, while supplementa…

L-Carnosine

Carbonyl and glycation defense — evidence-graded deep dive

Carnosine scavenges reactive carbonyls and buffers pH, but oral hydrolysis by carnosinase and small heterogeneous trials…

TMG (Trimethylglycine / Betaine)

BHMT methyl donation — evidence-graded deep dive

Betaine donates methyl groups through BHMT and reliably lowers homocysteine; performance and longevity implications are …

Tocotrienols (Vitamin E)

Lipid redox protection — evidence-graded deep dive

Tocotrienols are vitamin-E isoforms distinct from alpha-tocopherol, with human trials in lipids and metabolic or liver e…

Butyrate (Sodium / Tributyrin)

SCFA and HDAC signaling — evidence-graded deep dive

Butyrate is a colonocyte fuel and HDAC-active microbial metabolite; oral-product evidence is emerging and increasing fer…

Ashwagandha (Withania somnifera)

Stress-response modulation — evidence-graded deep dive

Standardized extracts have human evidence for perceived stress and sleep, while longevity claims are indirect and rare l…

Rhodiola rosea

Stress and fatigue signaling — evidence-graded deep dive

Rhodiola has modest human evidence for fatigue and stress, but study quality varies and lifespan findings are preclinica…

Nicotinamide (NAM)

NAD precursor and DNA repair — evidence-graded deep dive

Nicotinamide is a non-flushing vitamin-B3 form with strong evidence for reducing new non-melanoma skin cancers in high-r…

Hesperidin

Endothelial flavanone signaling — evidence-graded deep dive

This citrus flavanone has human vascular and inflammatory studies, with effects influenced by formulation and individual…

Boswellia serrata (AKBA)

5-LOX inflammatory signaling — evidence-graded deep dive

Standardized boswellic-acid extracts have reasonable evidence for osteoarthritis pain and function, while systemic longe…

Gynostemma pentaphyllum (Jiaogulan)

AMPK-linked metabolic signaling — evidence-graded deep dive

Small human studies suggest metabolic effects from gypenosides, but replication, product standardization, and healthspan…

Low-Dose Lithium

GSK-3 and autophagy signaling — evidence-graded deep dive

Ecological and preclinical signals are hypothesis-generating only; even low exposure can affect thyroid and kidney funct…

Hyaluronic Acid (Oral)

Extracellular-matrix hydration — evidence-graded deep dive

Oral hyaluronic acid has modest trials for skin hydration and knee symptoms, but absorption mechanisms and long-term hea…

Inulin / Prebiotic Fiber

Microbiome SCFA production — evidence-graded deep dive

Inulin-type fructans feed saccharolytic microbes and can improve bowel and selected metabolic outcomes; tolerance is dos…

Acarbose

Post-meal glucose attenuation — evidence-graded deep dive

Acarbose extends mouse lifespan in the NIA Intervention Testing Program and improves postprandial glucose in humans, but…

Canagliflozin (SGLT2 inhibitor)

Renal glucose excretion — evidence-graded deep dive

SGLT2 inhibition has strong cardiorenal outcome data in indicated patients and male-mouse lifespan data, but it is not a…

Tier CRx

17-alpha-Estradiol

Sex-specific metabolic signaling — evidence-graded deep dive

17-alpha-estradiol extends lifespan in male mice in the NIA program, but has no human longevity evidence and should be t…

Tier CRx

Dasatinib

Senolytic tyrosine-kinase inhibition — evidence-graded deep dive

Dasatinib plus quercetin has early human senolytic studies, but dasatinib is a potent leukemia drug with serious hematol…

Selenium

Selenoprotein Redox Defense — evidence-graded deep dive

Tier B for correcting insufficiency, not for general longevity. SELECT found no cancer-prevention benefit in largely rep…

PQQ (Pyrroloquinoline Quinone)

PGC-1alpha Mitochondrial Signaling — evidence-graded deep dive

Tier C: a 10-person crossover reported inflammatory and metabolic-marker shifts (PMID 24231099), while small cognition t…

Alpha-GPC (L-Alpha-Glycerylphosphorylcholine)

The choline form that reaches the brain — cholinergic support with real cognitive-decline RCTs

Bioavailable choline delivery that crosses the blood–brain barrier and raises synaptic acetylcholine. Tier B for cogniti…

Phosphatidylserine (PS)

Neuronal membrane phospholipid — cognitive support and the reproducible post-exercise cortisol lever

Membrane phospholipid essential to synaptic signaling. Crook 1991 age-associated memory RCT and Starks 2008 exercise-cor…

Ginkgo Biloba (EGb 761)

Vascular cognition — real effect in established dementia, negative for prevention (GEM trial)

Standardized EGb 761 (24% flavone glycosides, 6% terpene lactones) reduces cognitive decline in mild-moderate AD/vascula…

Panax Ginseng (Korean / Asian Ginseng)

Adaptogen with real fatigue-reduction and glycemic RCTs — cycle to prevent tachyphylaxis

Ginsenoside-rich root extract that dampens HPA axis output, improves insulin sensitivity, and supports mild cognitive vi…

Mucuna Pruriens (Velvet Bean, L-DOPA)

Natural L-DOPA — dopaminergic support that should be treated as a real drug, not just an herb

Seed cotyledons contain 3.6-6% pharmaceutical-identical L-DOPA. Katzenschlager 2004 Parkinson's crossover showed compara…

Theobromine

Cocoa's cardiovascular fraction — vasodilator, cough suppressant, and 7-hour half-life

The primary methylxanthine in cocoa (~10× more than caffeine by mass). Less CNS-stimulating than caffeine, more peripher…

Capsaicin (Cayenne / Chili)

TRPV1 agonist with a 14% mortality signal in China Kadoorie and topical Tier A for neuropathic pain

Chili-derived alkaloid that activates TRPV1 in brown adipose tissue, gut, and sensory neurons. Lv 2015 (487,375 adults) …

Pumpkin Seed Oil

Weak 5α-reductase modulator with the GRANU BPH trial and a real male-AGA hair-count signal

Lignan- and phytosterol-rich cold-pressed oil from Cucurbita pepo. Vahlensieck 2015 GRANU study (476 BPH men, 12 months)…

Superoxide Dismutase (SOD, Oral GliSODin)

Melon-derived SOD with gliadin coating — an Nrf2 signaling dose, not an enzyme-replacement supplement

Cucumis melo SOD extract complexed with wheat gliadin for GI protection. The mechanism is indirect Nrf2/ARE induction (n…

Piperine (BioPerine)

Black-pepper bioenhancer — 20× curcumin absorption, and a real drug-interaction concern

Piper nigrum alkaloid that inhibits intestinal UGT and P-glycoprotein, dramatically increasing systemic exposure to curc…

MCT Oil (Medium-Chain Triglycerides / C8:C10)

Portal-vein absorbed fats → ketones → the Cunnane MCI cognitive brain-fuel intervention

Medium-chain triglycerides bypass chylomicron packaging and go straight to the liver, where rapid β-oxidation produces k…

Bacopa Monnieri (Brahmi)

Ayurvedic nootropic — real memory consolidation at 8-12 weeks, no acute effect

Bacoside-standardized extract with genuinely delayed cognitive benefit — Stough 2001, Morgan 2010 meta, and Peth-Nui 201…

Cordyceps (Cordyceps militaris / sinensis)

Medicinal mushroom with a plausible mitochondrial mechanism and one honest older-adult VO₂max RCT

Cordycepin- and β-glucan-rich fungal extract with real preclinical mitochondrial-biogenesis story via AMPK/PGC-1α. Chen …

Reishi (Ganoderma lucidum)

"Spirit mushroom" of TCM — genuine immune mechanism, modest human evidence

Dual-extract Ganoderma lucidum captures both β-glucans (immune signaling) and triterpenoids (weak HMG-CoA reductase / st…

Turkey Tail (Trametes versicolor, PSK / PSP)

The best-evidenced medicinal mushroom — PSK is an approved oncology adjunct in Japan and China

Trametes versicolor polysaccharide extracts PSK (Krestin) and PSP have real meta-analytic survival benefit in gastric an…

Astragalus (Astragalus membranaceus)

The cycloastragenol / TA-65 telomere story — real, modest, and expensive

TCM immune tonic whose astragaloside IV / cycloastragenol fraction is the direct compound behind TA-65. Salvador 2016 CM…

Milk Thistle (Silymarin / Silybin)

Flavonolignan hepatoprotection — real NAFLD and diabetic-glycemic RCT evidence

Silybum marianum seed extract standardized to 70-80% silymarin, dominated by silybin. Loguercio 2012 NAFLD RCT (138 pati…

MSM (Methylsulfonylmethane)

Bioavailable sulfur for connective tissue and GSH substrate — modest knee-OA RCT signal

Dimethyl sulfone (oxidized DMSO) that supplies bioavailable sulfur for collagen crosslinks, glutathione synthesis, and p…

Chondroitin Sulfate

Cartilage glycosaminoglycan — MOVES showed non-inferiority to celecoxib for knee OA

Sulfated GAG structural component of cartilage. Fransen 2015 LEGS trial and Hochberg 2016 MOVES trial anchor the evidenc…

UC-II (Undenatured Type II Collagen)

Native chicken-sternum collagen at 40 mg/day — oral tolerance, not substrate; beats G+C in head-to-head RCTs

Undenatured type II collagen dosed intentionally low (40 mg/day) to induce gut-lymphoid oral tolerance to joint-derived …

Bromelain

Pineapple proteolytic enzyme — sports medicine and sinusitis workhorse, real anticoagulant potentiation

Ananas comosus stem thiol protease with genuine Tier B evidence in acute soft-tissue injury (Kerkhoffs ankle sprain), si…

Methylfolate (L-5-MTHF / L-Methylfolate)

The MTHFR bypass — bioactive folate for methylation-dependent variants

L-5-methyltetrahydrofolate bypasses the MTHFR enzyme bottleneck that 677C>T carriers hit with plain folic acid. Papakost…

Methylcobalamin (Active B12)

Direct-active B12 for age-related atrophic gastritis and methylation stacks

Directly-active B12 form used by methionine synthase without cellular reduction of cyanocobalamin. B12 deficiency preval…

P5P (Pyridoxal-5-Phosphate, Active B6)

The direct-active B6 coenzyme — bypass hepatic conversion, cofactor for 150+ enzymes

Pyridoxal-5-phosphate is the enzymatically-active B6 form, cofactor for homocysteine transsulfuration, neurotransmitter …

Benfotiamine (Fat-Soluble B1)

Transketolase activator that blocks all four AGE-formation pathways in hyperglycemia

Fat-soluble thiamine derivative with ~5× the bioavailability of thiamine HCl. Restores transketolase activity, which blo…

Niacin (Nicotinic Acid, Vitamin B3)

The lipid-modifying B3 form — dramatically raises HDL and lowers Lp(a), but AIM-HIGH/HPS2-THRIVE were negative

Nicotinic acid (flushing form of B3) modifies lipids potently: HDL +15-35%, LDL -5-25%, Lp(a) -20-30%. Coronary Drug Pro…

Vitamin C (Ascorbic Acid)

Essential cofactor for collagen and neurotransmitter synthesis; PHS-II negative for CV prevention

Essential water-soluble antioxidant; humans lack GULO gene. Padayatty 2004 established oral saturation at 200 mg BID — h…

Mixed Tocopherols (Full-Spectrum Vitamin E)

Preserve γ-tocopherol — SELECT and Miller meta made isolated α-tocopherol a bad bet

Vitamin E is 8 molecules, not just α-tocopherol. SELECT (17% ↑ prostate cancer) and Miller 2005 (↑ mortality at ≥400 IU …

Iodine

Essential thyroid substrate — deficiency is quietly returning as iodized salt use falls

Essential for T3/T4 synthesis. NHANES data shows median urinary iodine in US women of childbearing age has fallen from 3…

HMB (β-Hydroxy β-Methylbutyrate)

The strongest RCT evidence for preventing muscle loss during bed rest, hospitalization, and sarcopenia

Leucine metabolite (~5% of dietary leucine → HMB) that inhibits ubiquitin-proteasome muscle protein degradation and stab…

Trigonelline (Frontier NAD+ Precursor)

The 2024 NAD+ story — elevated in centenarians, restores muscle mitochondrial function in aged models

Nestlé Research / EPFL's 2024 identification that plasma trigonelline is elevated in Sardinian centenarians vs age-match…

Krill Oil (Phospholipid Omega-3)

Phospholipid-bound EPA/DHA plus astaxanthin — higher bioavailability per mg than fish oil

Antarctic krill (Euphausia superba) oil delivers omega-3s in phospholipid form (mostly PC) with ~50% higher bioavailabil…

PEA (Palmitoylethanolamide)

Endogenous PPAR-α agonist — "endocannabinoid without CB1" with real meta-analytic pain evidence

Naturally-occurring fatty acid amide that activates PPAR-α, stabilizes mast cells, and potentiates endogenous anandamide…

L-Arginine

eNOS substrate for endothelial NO — but VINTAGE-MI is a hard post-MI contraindication

Semi-essential amino acid, the sole substrate for endothelial NO synthase. Real evidence for erectile dysfunction, endot…

Acetyl-L-Carnitine (ALCAR)

Brain-penetrant carnitine — Tier B for DPN, MCI, and depression with a large evidence base

Acetylated carnitine crosses the blood-brain barrier and delivers both mitochondrial fatty-acid transport and acetyl for…