AMPA receptor potentiation
Increased acetylcholine turnover
Membrane fluidity enhancement
Mitochondrial function improvement
NMDA receptor modulation

memory consolidation
verbal learning
cognitive processing speed
neuroprotection

severe renal impairment
hemorrhagic stroke

potentiates stimulants
anticoagulants (slight)

headache (choline deficiency)
brain fog at low choline
insomnia if taken late
irritability

Piracetam

Always stack with choline source (Alpha-GPC or CDP-choline) to prevent headaches and potentiate effects

Alzheimer's research (mixed)
aphasia improvement
cognitive aging
alcoholic cognitive deficit

The original racetam. Good baseline. Effects subtle but real at high doses. Foundational compound.


AMPA receptor positive allosteric modulator

anxiety reduction
holistic/creative thinking
mood enhancement
verbal fluency
memory

headache (choline deficiency)
digestive upset
irritability

Aniracetam

anxiety disorders
ADHD adjunct
cognitive aging
stroke rehabilitation

Best racetam for mood/anxiety + cognition. Popular in creative fields. Short half-life requires multiple doses.


Neuroprotective via membrane phosphatidylcholine

focus
working memory
power output
racetam potentiation
GH pulse

headache at high doses
depression (rare)
fatigue
GI upset

Alpha-GPC

Alzheimer's disease
stroke recovery
age-related cognitive decline
athletic performance

Best choline source for CNS. Superior BBB penetration vs choline bitartrate. Essential companion for racetams.

acetylcholine maximization — use cautiously


Dopamine reuptake inhibition (DAT)
Norepinephrine reuptake inhibition
Orexin/hypocretin system activation
Histamine H3 receptor antagonism
Glutamate enhancement, GABA reduction

wakefulness
executive function
working memory
motivation
fatigue resistance

low — much lower than traditional stimulants

hypersensitivity
left ventricular hypertrophy
Tourette syndrome

CYP3A4 inducer — reduces hormonal contraceptives efficacy

insomnia
headache
nausea
anxiety
appetite suppression
skin reactions (rare SJS)

Modafinil

narcolepsy (FDA approved)
shift work disorder
military cognitive performance
ADHD adjunct

Gold standard for wakefulness and executive function. Non-stimulant mechanism. Avoid daily use to prevent tolerance. Excellent for shift work and demanding cognitive tasks.


NGF (Nerve Growth Factor) stimulation via hericenones

Myelination support via erinacines (cross BBB)

neurogenesis
memory long-term
anxiety reduction
nerve regeneration
gut health

Fruiting body extract > mycelium. Look for >30% beta-glucans, confirmed erinacines content.

autoimmune (theoretical — immunomodulatory)

anticoagulants (theoretical)
immunosuppressants (caution)

GI discomfort (rare)
allergy (mushroom sensitive)
mild stimulation

Lion's Mane (Hericium erinaceus)

MCI improvement 2009 Mori
anxiety/depression
peripheral nerve regeneration
gut microbiome

Only nootropic with credible neurogenesis evidence in humans. Long-term compound — 8+ weeks for full effect. Quality varies enormously between products.

stress resilience + cognitive protection


Protein kinase C activation in hippocampus

Antioxidant — reduces lipid peroxidation

memory consolidation
learning speed
anxiety reduction
neuroprotection

thyroid disorders (may reduce T4)
bradycardia

thyroid medications
sedatives (additive)
CYP450 interactions

nausea
GI cramping
dry mouth
fatigue early on

Bacopa Monnieri

bacosides A & B
bacopasaponins
alkaloids

memory in elderly (multiple)
ADHD children
anxiety
cognitive aging

Best studied natural nootropic for memory. Effect is cumulative — don't judge in first 2 weeks. Nausea common early, take with food.


Neuroprotection via oxidative stress reduction

executive function
working memory
motivation
ADHD symptoms
neuroprotection
stroke rehabilitation

mental health conditions (BDNF implications)

nasal irritation
mild anxiety at high doses
fatigue post-cycle

Semax

ADHD children (Russia)
stroke recovery
cognitive aging
optic nerve disease

Underrated peptide with strong evidence base (mostly Russian). Intranasal is convenient and fast. Stack with Selank for anxiety-free cognitive boost.

anxiety + cognitive combo — 'Russian stack'


Neuroprotection vs glutamate excitotoxicity

memory learning neuroprotection mood focus

irritability
brain fog (paradoxical)
headache
insomnia

very low — 1000x more potent than piracetam by weight

moderate (primarily Russian/Eastern European)

Noopept (Omberacetam)

cognitive impairment
Alzheimer's adjunct
anxiety-cognitive combo

Extremely potent per mg. Start low (10mg). Good value. Cycles recommended to prevent tolerance.


Cortisol reduction (11β-HSD1 inhibition)

Testosterone upregulation (LH potentiation)

stress reduction
anxiety
testosterone
strength/recovery
thyroid function
sleep quality

hyperthyroidism
autoimmune (theoretical)
pregnancy

thyroid medications
immunosuppressants
sedatives

GI upset
drowsiness
thyroid overstimulation

Ashwagandha (KSM-66)

cortisol reduction RCT
testosterone increase
strength performance
anxiety
thyroid function

Best studied adaptogen. KSM-66 > Sensoril for testosterone; Sensoril better for anxiety. Quality varies — check withanolide %. One of most evidence-backed supplements overall.


Dopamine receptor density upregulation
Norepinephrine potentiation
Acetylcholine enhancement
Alpha-adrenergic agonism
Psychomotor stimulation

stimulation
focus
physical performance
cold resistance
cognitive speed

cardiovascular issues
hypertension
anxiety disorders

insomnia
irritability
anxiety
rapid tolerance

Phenylpiracetam

epilepsy adjunct
stroke recovery
cognitive impairment

The stimulant racetam. Banned by WADA. Reserve for demanding days — tolerance develops within 3 consecutive days. More stimulating than modafinil.


VEGF upregulation — promotes angiogenesis

Tendon and ligament healing
Gut healing (IBD, leaky gut, ulcers)
Muscle healing post-injury
Joint repair
Neuroprotection
Systemic anti-inflammation

Poor systemic bioavailability but locally active in GI tract

theoretical due to angiogenesis promotion — not demonstrated in practice

active cancer (VEGF concern theoretical)

NSAIDs may reduce efficacy (competing pathways)

limited formal trials — primarily rodent data + anecdotal human use

growth stimulation concern (theoretical)

very low — no LD50 established in rodents even at extreme doses

extensive — hundreds of studies in rodents

limited formal trials, extensive community reports

One of the most popular research peptides. Exceptional safety profile in animal data. 'The wolverine peptide'. Gut healing at oral doses is well evidenced. Systemic repair requires injection.

comprehensive injury healing — the gold standard combo


Actin sequestering — promotes cell migration

Anti-inflammatory (down-regulates inflammatory cytokines)

Systemic tissue repair
Chronic injury healing
Cardiovascular protection
Anti-fibrotic
Flexibility improvement
Wound healing
Hair regrowth

Phase I/II trials (cardiac repair) — generally well tolerated

injection site pain
head rush (brief)
fatigue
nausea (rare)

Works systemically, not just locally. Excellent for chronic/old injuries that have stopped healing. The BPC-157 + TB-500 combo is considered the biohacking standard for repair.

synthetic fragment of endogenous Thymosin Beta-4

The classic combo — complementary mechanisms, comprehensive healing


No cortisol or prolactin increase (unlike other GHRPs)

GH pulse stimulation
fat loss
muscle preservation
sleep quality
recovery

before bed (strongest GH pulse during sleep)

insulin — timing
glucocorticoids reduce effect

tingling/numbness (carpal tunnel at high GH)

Ipamorelin

Cleanest GHRP — no cortisol/prolactin spike unlike hexarelin or GHRP-2. Best option for long-term GH optimization. Stack with CJC-1295 for 3-5x amplification.

The gold standard GH stack — GHRH + GHRP synergy, 3-5x GH pulse


Sustained GH secretion via DAC (half-life extension)

sustained GH elevation
IGF-1 increase
muscle growth
fat loss
recovery
anti-aging

1-2x per week (due to long half-life from DAC)

CJC-1295 without DAC = Mod GRF 1-29 — very different dosing (2-3x/day)

active cancer
diabetes
acromegaly
pregnancy

water retention
joint pain (GH related)
fatigue
hypoglycemia (rare)

CJC-1295 (with DAC)

Drug Affinity Complex Growth Hormone Releasing Factor

The 'set and forget' GH peptide — once or twice weekly dosing. Always stack with a GHRP for synergistic effect.

Best GH stack — amplified pulsatile release


Enkephalinase inhibition (endorphin preservation)

Dopamine, serotonin, norepinephrine balance

anxiety elimination
cognitive clarity
stress resilience
mood stabilization
memory

mild sedation
nasal irritation (intranasal)

Selank

Non-addictive anxiolytic with cognitive-enhancing properties. Approved in Russia. Used as benzodiazepine alternative.

The 'Russian stack' — anxiety-free cognitive enhancement


Anti-inflammatory gene activation (>4000 genes modulated)

skin repair and anti-aging
wound healing
hair regrowth
anti-inflammation
systemic repair

One of the safest peptides — naturally occurring, declining with age

copper excess at very high doses (theoretical)

strong for topical, moderate for systemic

GHK-Cu (Copper Peptide)

Naturally produced by the body, declines with age. Endocrine disruptor in skin aging. Strong anti-aging profile — modulates thousands of genes.


Telomerase activation (hTERT upregulation)

Pineal gland stimulation → melatonin normalization

telomere lengthening
longevity
sleep normalization
anti-cancer (reported)
immune optimization

active cancer (theoretical — telomerase)

injection site reaction
vivid dreams (melatonin effect)

moderate — Khavinson Institute data (Russia)

Epithalon (Epitalon)

limited formal trials, longitudinal Khavinson studies

The longevity peptide. Most researched peptide for life extension. Khavinson's research spans 40+ years. Annual courses common in longevity protocols.


mTORC1 inhibition via FKBP12 complex
Autophagy induction
Senescent cell burden reduction
Immune system rejuvenation
Translation regulation

Classical transplant-derived approach, higher side effect risk

Explanation: mTORC2 sparing — reduces metabolic side effects

active infection
immunocompromised baseline
pregnancy

CYP3A4 substrate — grapefruit, many drugs

immunosuppression
insulin resistance
hyperlipidemia
mouth sores
impaired wound healing

Rapamycin (Sirolimus)

deregulated nutrient sensing
cellular senescence
stem cell exhaustion
loss of proteostasis

Phase I/II trials in elderly immune function (Stanford, TRIIM-X)

strongest longevity evidence of any compound

AMPK + mTOR — complementary nutrient sensing pathways


Complex I mitochondrial inhibition → AMPK activation

start 500mg, increase slowly to reduce GI side effects

eGFR <30
hepatic failure
IV contrast (hold 48h)
alcoholism

may blunt mitochondrial adaptations from exercise — consider timing

GI upset (nausea, diarrhea) — dose-dependent

lactic acidosis (rare — contraindicated in renal failure)

blunts exercise adaptations (controversial)

Metformin

deregulated nutrient sensing
mitochondrial dysfunction
chronic inflammation
cellular senescence

Some longevity researchers (Peter Attia) suggest metformin may blunt exercise benefits and is not recommended for fit, metabolically healthy individuals. Debate ongoing.

prescription (diabetes / off-label longevity)

epidemiological association with reduced multiple cancers

diabetics on metformin outlive matched non-diabetic controls (Bannister 2014)

modest lifespan extension in some studies

Targeting Aging with Metformin — ongoing FDA trial

counter NAD+ depletion from Complex I inhibition


Direct NAD+ precursor (bypasses rate-limiting NAMPT)

NAD+ feeds cancer cell metabolism (theoretical — not demonstrated as harmful in humans)

nausea at high doses
flushing (less than niacin)
GI upset

NMN (Nicotinamide Mononucleotide)

strong — multiple lifespan and healthspan studies in mice

safety established, efficacy endpoints still emerging

mitochondrial dysfunction
genomic instability
deregulated nutrient sensing
stem cell exhaustion

NMN → NMN transporter (Slc12a8) → intracellular → NMN adenylyltransferase → NAD+

Sinclair protocol — SIRT1 activation + NAD+ substrate

methyl donor — prevents methylation depletion from NMN

Nicotinamide Riboside — must convert to NMN first

ongoing — absorption and tissue distribution differs

Imai 2020 (WUMS) — safe, raises NAD+ in blood


Senescent cell elimination (apoptosis induction)

BCL-2/BCL-XL inhibition in senescent cells

Anti-inflammatory (NF-κB, AP-1 inhibition)

Explanation: senolytic effect — intermittent high dose clears senescent cells

poor oral bioavailability — take with fat, consider liposomal form

Fisetin

strawberries (highest)
apples
persimmons
onions
cucumbers

cellular senescence
chronic inflammation
genomic instability

late-life treatment extended median lifespan 10%, improved healthspan markers


Quercetin

Senolytic (BCL-2 family inhibition — weaker than dasatinib)

quercetin phytosome (better bioavailability)

Quercetin 1000mg + Dasatinib 100mg (prescription)

quinolone antibiotics (spacing required)


Epigenetic — histone deacetylation inhibition

Mitochondrial membrane potential restoration

wheat germ is most concentrated natural source

very low — endogenous compound declining with age

Spermidine

wheat germ (highest)
soybeans
mushrooms
peas
blue cheese

yeast, worms, flies, mice — consistent lifespan extension

Mediterranean diet spermidine intake correlates with longevity

autophagy markers, cardiovascular benefit, cognitive aging


TCA cycle substrate — mitochondrial energy

Prolyl hydroxylase substrate → HIF-1α regulation

Epigenetic regulation via α-KG dependent dioxygenases (TET, JHDM)

Collagen synthesis support (prolyl hydroxylase)

Alpha-Ketoglutarate (AKG)

Maksim Khvorova / UCLA — 12% median lifespan extension, health parameters improved

mitochondrial + epigenetic comprehensive


Mitophagy induction (selective autophagy of damaged mitochondria)

Mitopure (Amazentis) — standardized urolithin A

Only ~40% of people have gut bacteria to produce from food — supplement bypasses this

Urolithin A

Amazentis Phase II — muscle function in elderly, safe and effective

gut microbiome metabolite of ellagitannins (pomegranate, walnuts)


gynecomastia | fatigue | low libido | loss of muscle mass | depression

Testosterone (Total)

SHBG affects free testosterone
LH indicates cause of low T
E2 balance critical

resistance training — compound lifts
sleep 7-9h (GH/T axis)
zinc 30-45mg/day
vitamin D 5000IU/day
ashwagandha KSM-66 600mg
reduce cortisol
body fat <20%
fadogia agrestis (preliminary)
tongkat ali (LJ100 extract)

gynecomastia
fatigue
low libido
loss of muscle mass
depression

fasted, morning (7-9am), no exercise 24h prior


More actionable than total T — bioavailable fraction

Free Testosterone

nettle root extract
optimize insulin sensitivity

boron 10mg/day reduces SHBG
weight loss
avoid excess alcohol


Too low is as bad as too high for males. Critical for bone, libido, cardiovascular.

Estradiol (E2)

water retention
gynecomastia
mood issues
fatigue

joint pain
low libido
brain fog
poor bone density

DIM (diindolylmethane) 200mg — shifts 2-OH pathway

body fat reduction (aromatase reduction)


TENSION: higher IGF-1 = muscle/performance; lower = longevity (mTOR/cancer). Context matters.

GH pulsatility
sleep quality
protein intake
insulin sensitivity
liver health

optimize sleep — deep sleep GH pulse
GHRP peptides (research)
resistance training
adequate protein 1.6-2.2g/kg


Cortisol (AM)

muscle catabolism
insulin resistance
hippocampal shrinkage
immune suppression
T3 conversion inhibition

cold exposure (acute cortisol, chronic adaptation)


Standard range too wide. Optimal is lower end.

TSH (Thyroid Stimulating Hormone)

Free T4
Free T3
Reverse T3
TPO antibodies
thyroglobulin antibodies

fatigue
cold intolerance
weight gain
brain fog
hair loss
constipation

iodine (careful — can worsen autoimmune)


Even 'normal' range upper end associates with increased risk. Optimal is lower.

Fasting Glucose

berberine 500mg 3x/day (comparable to metformin)

resistance training — insulin sensitization


3-month average glucose. Best single metabolic marker for longevity.

CGM monitoring for personalized response


Most labs don't flag until >25. Optimal is <6. Hyperinsulinemia is silent.

Insulin (fasting)

promotes fat storage
mTOR activation
accelerated aging
cancer promotion
cardiovascular risk

time-restricted eating
low-glycemic diet
berberine
resistance training
metformin
avoid snacking — longer fast windows


Best cardiovascular risk predictor — counts all atherogenic particles. Superior to LDL-C alone.

ApoB

statins (if indicated)
pcsk9 inhibitors (aggressive)
low-saturated fat diet
omega-3 high dose 4g EPA/DHA
berberine + RYR
exercise
weight loss


hsCRP (high-sensitivity C-reactive protein)

Key inflammaging marker. Even mildly elevated CRP predicts all-cause mortality.

metabolic syndrome
gut dysbiosis
sleep apnea
dental disease
food sensitivities
hidden infection

omega-3 EPA/DHA 3-4g/day
curcumin + piperine
resolution of gut issues
sleep optimization
exercise
weight loss
dental hygiene
low-AGE diet


Cardiovascular + Alzheimer's risk marker. Very modifiable.

Homocysteine

MTHFR polymorphism
B12 deficiency
folate deficiency
B6 deficiency
renal impairment
hypothyroidism

methylfolate (5-MTHF) 400-800mcg
methylcobalamin B12 1000mcg
P5P (activated B6) 50-100mg
betaine (TMG) 2-3g
riboflavin (B2)


K2 routes calcium to bones not arteries. Magnesium required for D3 activation.

Vitamin D (25-OH)

Vitamin K2 (MK-7) 200mcg
Magnesium 400mg


RBC magnesium is far superior to serum — reflects intracellular stores

Magnesium (RBC)

~45% of population subclinically deficient

poor sleep
muscle cramps
anxiety
insulin resistance
hypertension
migraines


Very low = iron deficiency (energy/cognitive). Very high = oxidative stress, hemochromatosis.

Ferritin

blood donation — most effective
IP6 (inositol hexaphosphate)
reduce heme iron intake
curcumin

iron bisglycinate (gentlest form)
vitamin C with iron
address underlying cause


Omega-3 Index

among strongest supplements for cardiovascular, brain, inflammation


Epigenetic Age (Horvath Clock / DunedinPACE)

dietary restriction / caloric restriction

TruDiagnostic (TruAge)
Elysium Index
Chronomics

Biological age based on methylation patterns at ~350,000 CpG sites


Controversial — high variability between tests. DunedinPACE more actionable.

Telomere Length

exercise
stress reduction
cycloastragenol (TA-65)
epithalon peptide


Peak mental performance, executive function, sustained focus

Morning Cognitive Stack

2-4 weeks for full effect on memory. Immediate effect on focus (modafinil/caffeine).

20-30min exercise before stack (BDNF boost)


Accelerate healing of tendons, ligaments, muscles, gut

Injury Healing Protocol

Blood flow restriction training (BFR) for injured limb

Acute injury: noticeable in 2-4 weeks. Chronic injury: 6-12 weeks.


Maximize endogenous testosterone production without exogenous hormones

Testosterone Optimization (Natural)

20-40% in clinically low individuals. Less in already-optimal.

Compound lifting 4x/week (squats, deadlifts, bench)

Sleep 8h — testosterone peaks in deep sleep

Reduce chronic stress — cortisol antagonizes T

Sauna 3-4x/week (heat shock proteins, testicular cooling after)

Test total T, free T, E2, LH, FSH at baseline and 3 months


Longevity Core Stack (Bryan Johnson inspired)

Comprehensive hallmarks of aging coverage for healthspan extension

may blunt exercise — consider cycling off on training days

Annual bloodwork panel + epigenetic age test

Conservative version — consult physician before rapamycin/metformin


Maximize endogenous GH pulsatility, IGF-1, body composition

3x daily SC — AM, pre-workout, before bed

oral ghrelin mimetic — alternative to injectables

GH Optimization Stack

Sleep optimization — peak GH in first 90min

IGF-1 baseline and monthly
glucose/insulin (MK-677 can raise)
fasting insulin

Research peptides — gray market. Educational purposes.


Deep sleep optimization, HRV improvement, overnight recovery

reduces core body temp, improves deep sleep

lower dose more physiological — avoid 5-10mg

Sleep & Recovery Protocol

Dark room + cold (18°C/65°F) — core body temp reduction

No blue light 2h before bed (or blue-blockers)

Consistent sleep/wake time — circadian anchoring

No alcohol (fragments sleep architecture)


Autophagy induction (16h+ fasting) | Insulin sensitivity improvement | mTOR suppression during fast | Circadian rhythm alignment | Weight management | Reduced inflammation

Autophagy induction (16h+ fasting)
Insulin sensitivity improvement
mTOR suppression during fast
Circadian rhythm alignment
Weight management
Reduced inflammation

5 normal days, 2 days at 500-600 kcal

Time-Restricted Eating (TRE)

Coffee/tea (no calories) allowed in fast

Break fast with protein + fat, not carbs (insulin management)

Adjust protein timing — prioritize post-training

earlier in day (8am-4pm) aligns with circadian biology — superior metabolic outcomes vs late eating

5 normal days, 2 days at 500-600 kcal


Protein Optimization

40g casein = 25-30% better overnight MPS

20-40g protein 1-2h pre improves performance


Ketogenic Diet for Performance & Cognition

Ketone bodies (BHB) — cleaner brain fuel | Reduced neuroinflammation | Metabolic flexibility | Appetite suppression (ghrelin reduction) | mTOR pulsatility vs chronic activation

BHB salts — large sodium load; esters — expensive, strong taste

acute cognitive performance before keto-adaptation

rapid ketone source, GI tolerance required


Omega-3 (EPA/DHA)

anti-inflammatory | cardiovascular | brain structure | insulin sensitivity | cortisol reduction

anti-inflammatory
cardiovascular
brain structure
insulin sensitivity
cortisol reduction

sardines
mackerel
wild salmon
anchovies
fish oil triglyceride form

Western diet EPA:DHA ratio often 1:3 (bad) — target closer to 1:1 or 2:1 EPA:DHA


Creatine Monohydrate

strength +5-15% | cognitive function (esp. vegetarians) | creatine kinase buffering | neuroprotection | anti-aging

strength +5-15%
cognitive function (esp. vegetarians)
creatine kinase buffering
neuroprotection
anti-aging

extremely strong — one of most studied supplements

creatine monohydrate — original, best studied

optional: 20g/day x 5 days then 5g maintenance


Berberine

blood glucose comparable to metformin in T2D | LDL -25% | triglycerides -35% | weight loss

AMPK activation (like metformin)
gut microbiome modulation
PCSK9 inhibition (lipids)
anti-inflammatory

Half-life 4-6h — require multiple doses. Dihydroberberine (DHB) = higher bioavailability, lower dose


Curcumin + Piperine

NF-κB inhibition
COX-2 inhibition
BDNF upregulation
autophagy
epigenetic

strong for inflammation, moderate for other claims

liposomal or phosphatidylcholine complex for best absorption


MTHFR C677T

elevated homocysteine | reduced SAM (methylation) | potential B12/folate deficiency despite 'normal' labs

Methylfolate (5-MTHF) not folic acid | Methylcobalamin not cyanocobalamin | Betaine (TMG) 1-3g/day | Monitor homocysteine

Reduced methylenetetrahydrofolate reductase activity — impaired folate metabolism

Methylfolate (5-MTHF) not folic acid
Methylcobalamin not cyanocobalamin
Betaine (TMG) 1-3g/day
Monitor homocysteine


APOE ε4

saturated fat → higher LDL response | omega-3 even more important | DHA uptake reduced

saturated fat → higher LDL response
omega-3 even more important
DHA uptake reduced

Higher omega-3 DHA supplementation | Reduce saturated fat (stronger response vs non-ε4) | Earlier cognitive interventions | Lion's Mane, Bacopa — neuroprotective priority

Increased Alzheimer's risk, altered lipid metabolism


VDR multiple

Target higher 25-OH D3 levels (80-100ng/mL vs 60-80)

Vitamin D receptor polymorphisms — reduced signaling


CYP1A2 rs762551

Slow metabolizers: limit caffeine to 1-2 cups, no afternoon caffeine

1A allele — caffeine cleared quickly, cardiovascular protective

1F allele — caffeine lingers, increased MI risk at high doses