Every brain is built to keep building.
Your brain keeps building for life: the hippocampus mints new neurons well into old age, and every network rewires around what you feed it. The aim here is simple, and it doesn't change with your age. Add what grows the brain, drop what wears it down, and let the gains stack. Not just more years, but more years with the entire brain fully online.
The encouraging part is that the playbook doesn't change with where you start. A fifteen-year-old protecting a still-developing brain and a seventy-three-year-old sharpening an experienced one run the same logic: stack the behaviors and molecules that help, cut the ones that do damage, and let plasticity do what it's done your whole life. No baseline is too low. No age is too late. Every good input compounds from wherever you stand today.
Give it the right signals and raw materials and the brain answers by building. Deep sleep, movement, clean fuel, fewer toxins, real human contact: feed it those and it lays down new synapses, thickens myelin, and grows fresh neurons in the regions that hold memory. The animation below is that network, wiring itself for as long as you keep feeding it.
First, do no harm: subtract the brain-destroyers before you add anything. Then build, and the order matters: each layer only pays off once the one beneath it holds. Sleep is the foundation everything rests on. The most common mistake is reaching for a supplement before any of that is in place.
Start with two or three changes, not twenty. Protect deep sleep, drop your worst couple of inputs, and build from a base that actually holds. Small habits, kept up, compound across decades. That compounding is the whole game.
This protocol was lived before it was written. Years of self-experimentation tell you what helped one nervous system. They don't tell you which single input did the work, and they're not a clinical trial. Use the citations to check the mechanism, and a qualified provider to check it against your own biology.
Deep sleep is the brain's nightly self-cleaning cycle.
In N3 slow-wave sleep, waste is flushed, growth hormone peaks, and neurons restore. No molecule replaces it. Protect this window first, then build everything else on top of it.
During N3, brain waves slow to delta, noradrenaline bottoms out, and the brain's interstitial space opens by about sixty percent, letting cerebrospinal fluid wash through. That wash is the glymphatic system clearing metabolic waste, including the amyloid-β and tau proteins at the center of Alzheimer's. Almost all of it happens in deep sleep.
The night's biggest burst of growth hormone fires in the same window, driving tissue repair, immune function, and cellular regeneration. N3 only starts once noradrenaline hits its lowest point, which is why anything that keeps you aroused at night quietly steals it.
Deep sleep falls off with age. By your sixties you may have lost sixty to eighty percent of the N3 you had in your twenties. The loss feeds itself: poor sleep lets proteins build up, that buildup damages the circuits that generate deep sleep, and sleep gets worse from there. The cycle can run quietly for decades.
Mixed in water, thirty to sixty minutes before bed. The goal is to deepen slow-wave sleep, not just to sedate. A sedated brain isn't a cleaning brain, so that difference matters.
| Ingredient | What it does | Dose |
|---|---|---|
| Glycine | Lowers core temperature, deepens N3, glutathione precursor | 3–7 g |
| L-theanine | Alpha waves, boosts delta power without sedation | 100–400 mg |
| Magnesium bisglycinate | GABA tone, muscle relaxation, gates NMDA | 200–400 mg |
| Lemon balm extract | Raises GABA; +15% deep sleep in a 2024 trial | 300–600 mg |
Add NAC to the drink, or pair it with your morning NAC, and the glycine-plus-NAC combination becomes GlyNAC: the two-part precursor your body uses to rebuild glutathione, the rate-limiting antioxidant of the whole system.
| Input | Window | Why |
|---|---|---|
| Blue light | 2–3 h before | 446–480 nm light suppresses melatonin and specifically reduces deep sleep. Amber glasses or warm dim light after sunset. |
| Food | 2–4 h before | Active digestion raises core temp, blood sugar, insulin, and sympathetic tone, all working against N3. |
| Alcohol | None within 3–4 h | Speeds onset but suppresses N3 and REM in the second half, gutting the cleaning window. |
| Nicotine | None within 4–6 h | A stimulant that fragments sleep and feeds the same catecholamine load as caffeine. |
| Hard exercise | Finish 4–6 h before | One of the strongest deep-sleep enhancers, but not too late, or arousal blocks onset. |
| Demanding mental work | Cut ~8 PM | A wired brain can't drop into deep sleep on command. Keep screens out of bed. |
Two genes decide how stimulants hit your sleep. CYP1A2 clears caffeine from your blood. COMT clears the noradrenaline and dopamine it set off in your brain. COMT is the one that matters more: even after the caffeine is gone, those stress chemicals still have to clear before noradrenaline can bottom out and N3 can start.
| Profile | What it means | Caffeine cutoff |
|---|---|---|
| Everyone | Check evening teas for hidden caffeine | none after 12–2 PM |
| Slow COMT (Met/Met, ~25%) | Clears catecholamines at ~¼ speed | before 10 AM / none |
| Slow CYP1A2 + COMT | Both pathways compromised | decaf only |
Signs you may be a slow COMT metabolizer: racing thoughts at bedtime despite physical tiredness, a "wired but tired" evening, shallow unrefreshing sleep even with enough hours, low deep sleep on a tracker, caffeine sensitivity out of proportion to the dose, anxiety that builds through the day, and trouble switching off after stress.
A morning coffee can quietly block tonight's deep sleep if you clear catecholamines slowly. When energy flags, the answer for a slow-COMT brain is more sleep, not more drive.
When deep sleep fails, the glymphatic system can't clear misfolded proteins. And every major neurodegenerative disease is, at its core, a buildup of one.
| Protein | Disease | Sleep link |
|---|---|---|
| Amyloid-β + Tau | Alzheimer's | A single night of poor sleep produces measurable amyloid buildup on PET. |
| α-Synuclein | Parkinson's | Enhancing deep sleep reduces α-synuclein in animal models. |
| TDP-43 | ALS | Glymphatic impairment shows up before motor symptoms appear. |
You can't improve what you can't see. A sleep wearable lets you watch your N3 trend night to night and test whether the drink, the cool room, and the caffeine cutoff are actually deepening it. The Oura ring is the one I track with: it estimates deep sleep alongside the overnight HRV and body-temperature shifts that move with recovery and brain restoration. Honest caveat: no finger or wrist wearable matches a sleep lab on any single night, but the trend over weeks is what you act on, and it's good enough to tell whether a change is working.
Referral link, which supports this work at no extra cost to you.
Exercise is the most reliable lever on BDNF.
Movement drives three things at once: brain-derived neurotrophic factor, cerebral blood flow, and mitochondrial health. Those are the raw materials of neuroplasticity. The dose is what matters. Build the aerobic base, add intensity sparingly, and don't let training turn into another stressor.
This tab is the why and the what. The Regenerative Fitness Program™ is the how: the same week above, programmed, timed, and tracked for you. It's a web app built by Matt O'Connor (trained under Mike Boyle), bookmarked to your phone and opened at the gym.
The Regenerative Fitness Program™
One purchase, one link, a lifetime of training. The dose that regenerates instead of grinds.
Physical training builds the hardware; cognitive challenge builds the wiring. The brain keeps what it's forced to use, and novelty is the active ingredient. This is some of the strongest research in the field: the ACTIVE trial found that speed-of-processing training, the format behind apps like BrainHQ, lowered later dementia risk years out. The catch is that it has to be genuinely hard and genuinely new. A crossword you breeze through is maintenance. A skill you're bad at is growth.
Neurons that fire together wire together, and what you don't use, you lose. So the brain needs demand every week, and it has to stay varied, cognitively and physically. Novelty and rising difficulty beat comfortable repetition: the moment something feels easy, it has stopped building.
Brief, controlled stress makes the system adapt and come back stronger. The same logic as training: a dose the body has to rise to meet. Two stand out, with honest weighting on the evidence.
Build the Zone-2 base most days, lift two or three times a week, walk daily, and train the mind on something hard and new. Move the body, then stretch the brain. Consistency beats intensity for both.
Feed the brain stable glucose and the right fats.
Whole-food fuel for a stable, resilient brain: balanced macros, steady glucose, and a few inputs worth pulling forward. What you subtract here often matters as much as what you add.
Barry Sears' framing is simple and durable: balanced macros at every meal for stable glucose to the brain. No glucose spikes, no crashes, no insulin roller-coaster running underneath your cognition all day.
Dr Barry Sears' hand reference for metabolic perfection at every meal:
A handful of inputs reliably push the brain back toward inflammation and instability. Pulling them often matters as much as anything you add. The full mechanisms live in the Subtract tab; here's the short version for the plate.
A few inputs earn their place by actively building, not just by being neutral fuel. Each one has human evidence behind it, with the honest caveats noted.
Two that get more hype than their evidence supports. Therapeutic ketosis is genuinely strong for epilepsy and acute brain injury, but the case for a healthy brain is still emerging and the diet is demanding, so treat it as an advanced experiment, not a baseline. Resveratrol crosses the brain well in theory but absorbs poorly in practice, and human cognitive results have been underwhelming. Neither is a foundation; the daily plate and the greens are.
If you run a large morning vegetable juice, the defensible reasons are hydration, electrolytes, and luteolin, a real anti-inflammatory flavonoid. The stronger evidence sits with luteolin as a compound, not with juice as a cure. Keep the expectation at "clean hydration with a useful flavonoid," and run anything bigger past a provider.
Balanced macros every meal, eat every 4–5 hours, blueberries and cruciferous daily, clean fats, and subtract the six inflammatory inputs. Steady glucose is the quiet baseline that everything cognitive rides on.
What quietly erodes the brain.
Twenty inputs that harm the brain, or that the brain treats as harmful: ten you take in, ten you do or fail to do. Most cause no symptom today. The damage is cumulative.
The strongest evidence here is for sleep loss, alcohol, refined sugar, and head impacts. A few items carry contested or emerging evidence: non-native EMF, mold/CIRS, microplastic harm, A1 casein, amalgam-to-Alzheimer's. Those entries keep their original hedges. Treat the well-settled items as priorities and the contested ones as reasonable precaution, not settled fact.
MechanismGliadin triggers zonulin release, which loosens intestinal tight junctions and allows systemic LPS translocation. Gliadorphin-7, a peptide fragment, has μ-opioid receptor activity and crosses a compromised blood-brain barrier, contributing to neuroinflammation and microglial activation. Found in wheat, rye and barley.
MechanismThe A1 variant of β-casein releases BCM-7 on digestion, an opioid heptapeptide. It promotes gut inflammation, slows intestinal transit, and in BBB-compromised states reaches the CNS, where its receptor activity correlates with cognitive and behavioral effects in animal models. A2-only dairy doesn't produce it. Human cognitive causation here is emerging, not established.
MechanismDirect neurotoxicity to hippocampal and prefrontal neurons, suppressed adult neurogenesis in the dentate gyrus, BBB tight-junction disruption, acetaldehyde adduct formation, and gut dysbiosis driving systemic LPS. Brain volume loss is dose-dependent with no safe threshold in current imaging data.
MechanismDaily high-THC cannabis (modern flower runs 15–25%) produces measurable reductions in cerebral blood flow on SPECT, with hippocampal and posterior cingulate hypoperfusion the most consistent finding. CB1 downregulation alters working memory, verbal learning and motivation. Vaporized flower shows the same pattern as combusted use, so route matters less than chronicity and dose.
ThresholdThe 2% line reflects that low-THC, CBD-dominant profiles don't reproduce the hypoperfusion signal. The mechanism scales with concentration and frequency, not delivery method.
MechanismGlutamate is the brain's primary excitatory neurotransmitter, and free dietary glutamate spikes plasma levels well above what bound protein produces. Chronic NMDA overactivation drives calcium-mediated excitotoxicity, particularly in BBB-compromised states (chronic inflammation, late life). Hides in yeast extract, hydrolyzed protein and "xxx flavor".
MechanismAdenosine antagonism produces cerebral vasoconstriction and reduces baseline blood flow. More important long-horizon: caffeine sustains elevated cortisol, especially in habitual users under stress. Decades of glucocorticoid pressure on hippocampal CA1/CA3 neurons drive measurable volume loss (Sapolsky's cascade).
Genotype · COMT Met/Met (rs4680 A/A)Met/Met carriers clear catecholamines at ~25–30% the speed of Val/Val, leaving prefrontal dopamine and norepinephrine already elevated. For them, stimulants of any kind (caffeine, cacao, green tea, matcha, rhodiola, L-tyrosine) push past the inverted-U optimum, bringing anxiety, jitter, working-memory degradation, and disrupted sleep with no net benefit. The clean play is to skip stimulants and trust the baseline.
MechanismPostprandial glucose spikes drive advanced glycation end-products that crosslink neural proteins. Chronic hyperinsulinemia produces brain insulin resistance, the basis for the "type 3 diabetes" framing of Alzheimer's. Hippocampal volume tracks inversely with average glucose even in non-diabetic ranges.
MechanismMethylmercury (large predatory fish) and elemental mercury vapor (amalgam fillings) cross the BBB and accumulate in the CNS, binding selenoproteins, driving oxidative stress and impairing microtubule formation. The strong mercury-toxicity evidence is well established; the direct amalgam-to-Alzheimer's causal claim is a minority position, so weight the caution toward exposure reduction rather than a settled causal story.
PracticalComposite or ceramic fillings only; remove amalgams via an IAOMT-certified dentist using SMART protocol. Avoid swordfish, shark, king mackerel, tilefish, marlin and large tuna. Wild Alaskan salmon, sardines, anchovies and Atlantic mackerel stay low-mercury. Cookware: cast iron, 18/10 stainless, glass, enameled cast iron. Skip PTFE nonstick.
MechanismMicro- and nanoparticles cross the gut barrier and have been recovered from human brain tissue at rising concentrations. They drive neuroinflammation and microglial activation in animal models. Plasticizers (phthalates, BPA, BPS) bind estrogen and thyroid receptors. Detection in brain tissue is established; the human-harm causation is still emerging.
PracticalGlass or stainless bottles. Filter tap water. Never microwave plastic. Glass food storage. Skip plastic tea bags (billions of particles per cup). Reduce synthetic textiles; avoid handling thermal-paper receipts.
MechanismMycotoxins from water-damaged buildings drive chronic inflammatory response syndrome (CIRS), mitochondrial dysfunction and direct neuroinflammation in affected individuals. They cross the BBB and correlate with executive-function and memory deficits in CIRS patients. CIRS as a diagnostic framework is contested in mainstream medicine; the entry is kept for precaution, not as settled consensus.
PracticalFor environmental mold, place agar plates in the sleeping environment overnight with a control plate elsewhere; compare colony density after 5–7 days. Order ERMI dust testing if it flags. Address visible water damage at source. Common dietary sources: conventional coffee, peanuts, corn, dried fruit, wine. Choose mycotoxin-tested coffee.
MechanismGlymphatic clearance of amyloid and tau happens predominantly during deep NREM sleep. Chronic restriction below seven hours measurably reduces clearance and accelerates deposition. Even one night of restriction raises amyloid in the hippocampus and thalamus on PET. See the full Sleep tab.
PracticalSeven to nine hours nightly. Cool dark room. Last meal three-plus hours before bed. Morning sunlight to anchor rhythm. Consistent wake time, even weekends.
MechanismChronic loneliness elevates IL-6, TNF-α and cortisol, with measurable hippocampal and prefrontal effects. An independent dementia risk factor comparable in magnitude to physical inactivity. The mechanism is biological, not just psychological: loneliness produces a distinct immune-cell gene-expression pattern.
MechanismVariable-ratio reinforcement produces phasic dopamine release indistinguishable from gambling. Over years this downregulates D2 receptor density and raises the threshold to feel engaged by lower-amplitude inputs like reading, conversation, and learning. Working-memory capacity tracks inversely with daily scroll time.
MechanismOn-demand novelty (the Coolidge effect) produces dopamine patterns the reward system didn't evolve to handle. Habitual use correlates with reduced right-caudate gray matter and reduced striatum–prefrontal connectivity on fMRI. Effects appear dose-dependent and reversible with extended abstinence.
MechanismThe same dopaminergic signature as social media and porn, plus competitive variable rewards on a 5–25 minute cycle for hours. Chronic exposure reduces sensitivity to slower, lower-amplitude rewards. Striatal dopamine release during gameplay matches the magnitude seen with stimulant administration.
MechanismDirect retinal exposure to morning light anchors the suprachiasmatic nucleus, which controls cortisol rhythm, melatonin onset and downstream cognition. The photic mechanism has independent effects on mood, sleep architecture and cognition; vitamin D is a secondary downstream factor.
FixTen to thirty minutes of morning sun on skin and eyes within an hour of waking. Midday sun for vitamin D, latitude-dependent. Glass blocks UVB, so the exposure has to be direct.
MechanismTime in green and blue spaces reduces sympathetic activation, lowers cortisol and restores directed attention. Subgenual prefrontal activity, the part tied to rumination, drops after a 90-minute nature walk versus an equivalent urban walk.
MechanismRadiofrequency and extremely-low-frequency fields are proposed to activate voltage-gated calcium channels below thermal thresholds. Pall's hypothesis links VGCC activation to oxidative stress, BBB disruption and neurological symptoms in sensitive individuals. The mechanism remains contested in mainstream literature; precautionary positioning is reasonable.
PracticalHardwired ethernet over Wi-Fi where feasible. Phone on airplane mode at night, away from the bed. Router on a timer overnight. Distance is the cheapest mitigation: intensity drops with the inverse square of it.
MechanismNicotine produces acute cerebral vasoconstriction and chronic endothelial dysfunction. Smoking adds oxidative load, carbon-monoxide oxygen displacement and tar-driven inflammation. An independent dementia risk factor on top of every cardiovascular pathway. Vaping is a milder version of the same vascular mechanism; long-horizon data is still emerging.
MechanismRepeated mechanical force to the head, even sub-injury "dings" that never register as a concussion, transiently disrupts the blood-brain barrier and seeds tau protein in vulnerable cortical regions. The exposure is cumulative with no symptom threshold required for accumulation: the damage adds up whether or not any single hit feels like anything. This entry is forward-looking prevention. The cleanest protection is simply choosing not to accrue the exposure in the first place.
Weigh carefullyCombat sports (boxing, MMA, kickboxing) are the most direct case. Collision sports (American football, rugby, ice hockey) carry repeated impacts as a feature of play, and repetitive soccer heading shows measurable effects in heading-exposure studies. Equestrian / horseback riding is among the higher-risk recreational activities for serious head injury, driven by falls from height and speed.
Blast & vibrationRepetitive blast overpressure (heavy-caliber or muzzle-braked firearms, breaching, artillery) drives neurological change through the pressure wave, not the recoil; the concern scales with frequency and caliber, not occasional target shooting. High-vibration exposure (some motorsport, powerboat racing) is included precautionarily; its evidence base is thinner than impact or blast.
PracticalHelmets reduce skull fracture and severe injury but do not prevent the rotational and subconcussive forces that drive tau accumulation, so "wear a helmet" is not a green light for collision exposure. The Exercise tab favors racket sports, Zone-2 cardio and lifting precisely because they build the brain without trading against it. Hearing and head protection, lower round counts, and non-contact alternatives are the levers.
You don't have to fix all twenty at once. Remove your worst two or three, watch what changes, and let the wins recruit the next change. Subtraction compounds the same way addition does.
A clean stack on a clean substrate.
Subtracting the brain-destroyers usually does more in the first month than any capsule added on top. But once the substrate is clean, a well-sequenced stack compounds across decades. Don't add everything at once. Subtract first, build the foundation, then layer.
None of this is prescriptive. Doses are starting ranges from the literature, not personalized instructions. Several items interact with blood thinners, blood-pressure and psychiatric medication. Review the stack with a qualified provider. And where it depends on your variants (COMT, GSTM1, MTHFR, ApoE), get those read first.
These come first, because food alone usually doesn't get you there. Omega-3, vitamin D, and magnesium run low even on a decent Western diet, across Europe, the US, and Canada, and they stay low without supplementing. Correct these before anything else, and test where you can.
1–2 g/day EPA+DHA · TG or phospholipid formThe brain is ~60% fat by dry weight, and DHA is the dominant structural fatty acid in synaptic membranes, supporting membrane fluidity, BDNF, and the resolution phase of inflammation via resolvins and protectins. Most Western diets run a low omega-3 index; without oily fish several times a week you won't reach sufficiency without a supplement. Low plasma DHA tracks with smaller brain volume and faster decline.
D3 2000–5000 IU to a 25-OH vitamin D of 40–60 ng/mL · K2 (MK-7) 100–200 mcgVitamin D receptors sit throughout the brain, where D regulates neurotrophic factors and dampens neuroinflammation; low levels track with faster decline. Deficiency is widespread, especially at higher latitudes and through winter. Test 25-hydroxy vitamin D and dose to target. K2 directs calcium into bone rather than arteries. The win is correcting the deficit, not pushing past a healthy level.
200–400 mg elemental, eveningMagnesium gates the NMDA receptor and supports GABAergic tone. Subclinical deficiency is widespread because most diets fall short of the RDA. Bisglycinate is well-absorbed and gentle on the gut; evening dosing also supports sleep onset and N3 depth.
5 g monohydrate daily · no loadingCreatine phosphate is the brain's high-speed ATP reserve, regenerating energy in milliseconds during cognitive demand. Supplementation raises brain creatine on MRS and improves rapid working memory. Largest effects in vegetarians, the sleep-deprived, and the elderly, populations starting from a depleted baseline.
B12 500–1000 mcg · methylfolate 400–800 mcg · P5P 25–50 mgThe methylation B-vitamins lower homocysteine, which is directly neurotoxic and accelerates brain atrophy when elevated. B12 builds myelin; folate is required for neurogenesis. In the VITACOG trial, B-vitamins slowed brain shrinkage in people with mild impairment, but the benefit was concentrated in those who started with high homocysteine. Test first and aim under 10 µmol/L; this is a correction for a deficit, not a universal nootropic.
500–1000 mg/day, split with foodThe brain concentrates vitamin C higher than any organ but the adrenals. A cofactor for dopamine β-hydroxylase, it supports BBB integrity and recycles glutathione and tocopherols to active form. Plasma C correlates with cognition across cohorts.
30 mg/day standardized (Affron, Viva+)Crocin and safranal cross the BBB and modulate dopamine, norepinephrine and serotonin. RCTs show antidepressant effects comparable to fluoxetine, plus cognitive benefit in MCI and mild-to-moderate Alzheimer's. No catecholamine-clearance burden, so COMT-safe.
300–600 mg/day standardized (e.g. Cyracos)Melissa officinalis raises GABA tone by slowing its breakdown, taking the edge off the low-grade stress and overstimulation of modern life without sedation. Trials show reduced anxiety and stress, better calm, and steadier attention under load. A daytime option when the nervous system runs hot.
250–500 mg/day · esp. for non-egg-eatersSplits into cytidine and choline, reused for membrane phospholipid synthesis and acetylcholine production. Vegetarians and non-egg-eaters often run low on choline; citicoline closes the gap. Attention and memory benefits in healthy and post-stroke populations.
Canadian practitioner dispensary: friends & family pricing, ships from Canada, billed in CAD.
Keep it boring and keep it small. Get three things sufficient first, the ones diet leaves short: omega-3, vitamin D, magnesium. Then a plain foundation, then a little for mood and calm. Test where you can, add one thing at a time, and remember the stack is the last layer, not the first.
A brain stuck in threat can't do the rest of the work.
Chronic stress load and unresolved trauma keep the brain inflamed and the nervous system locked in defense. These practices shift it back toward parasympathetic safety, the state where everything else in this guide can actually land.
Some load doesn't get down-regulated; it gets processed. Stored trauma keeps the HPA axis lit and the body braced. Two modalities have the strongest evidence base for actually resolving it rather than managing it.
Trauma processing belongs with a licensed professional. This is the one area where a skilled, qualified human matters most. Not a document, not a chatbot, not a protocol. If you're carrying a significant trauma load, the safest and most effective path runs through a trained clinician.
If years of phasic-dopamine inputs (social media, porn, gaming, stimulants) have flattened your baseline drive, motivation, and joy, the fix works upstream: receptor density, dopamine and serotonin tone, and the behavioral substrate that lets the rest of this guide take effect. Built for people who've read the science and now need a structured way to rebuild.
Down-regulate daily, process stored trauma with a professional, protect real human connection, and rebuild reward sensitivity if it's been flattened. A nervous system that feels safe is the precondition for every other gain in this guide.
Check the mechanism, then check it against you.
The references below let you verify the biology behind each claim. They establish mechanism and plausibility. They don't prove that any single input did the work in one person's case, and none of this substitutes for examination by a provider who knows your history.
Strongest support: sleep/glymphatic clearance, alcohol neurotoxicity, refined sugar, head impacts, omega-3, creatine, magnesium. Emerging or modest: NR, astaxanthin, SPM cognitive endpoints. Contested, kept for precaution: non-native EMF, CIRS/mold framework, microplastic harm causation, A1-casein cognition, amalgam-to-Alzheimer's. Where a finding is animal-model or in-vitro only, the entry says so.
Sleep & glymphatic clearance
Xie L, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013;342(6156):373-377.
Shokri-Kojori E, et al. β-Amyloid accumulation in the human brain after one night of sleep deprivation. PNAS. 2018;115(17):4483-4488.
Lee H, et al. The effect of body posture on brain glymphatic transport. J Neurosci. 2015;35(31):11034-11044.
Shechter A, et al. Blocking nocturnal blue light for insomnia: a randomized controlled trial. J Psychiatr Res. 2018;96:196-202.
Neurodegeneration & protein clearance
de la Monte SM. Type 3 diabetes is sporadic Alzheimer's disease: mini-review. Eur Neuropsychopharmacol. 2014;24(12):1954-1960.
Cherbuin N, et al. Higher normal fasting plasma glucose is associated with hippocampal atrophy. Neurology. 2012;79(10):1019-1026.
Topiwala A, et al. Moderate alcohol consumption as risk factor for adverse brain outcomes. BMJ. 2017;357:j2353.
Daviet R, et al. Associations between alcohol consumption and gray and white matter volumes. Nat Commun. 2022;13:1175.
Head impact & blast exposure (prevention)
McKee AC, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain. 2013;136(1):43-64.
Bailes JE, et al. Role of subconcussion in repetitive mild traumatic brain injury. J Neurosurg. 2013;119(5):1235-1245.
Stamm JM, et al. Age of first exposure to football and later-life cognitive impairment in former NFL players. Neurology. 2015;84(11):1114-1120.
Ling H, et al. Mixed pathologies including chronic traumatic encephalopathy in retired soccer players. Acta Neuropathol. 2017;133(3):337-352.
Carr W, et al. Repeated low-level blast overpressure in military personnel: relationship of exposure and neurological symptom reporting. Front Neurol. 2016;7:152. (blast-overpressure mechanism)
Gut–brain, dietary peptides & metals
Fasano A. Zonulin and its regulation of intestinal barrier function. Physiol Rev. 2011;91(1):151-175.
Hadjivassiliou M, et al. Gluten-related neurologic dysfunction. Handb Clin Neurol. 2014;120:607-619.
Pal S, et al. Milk intolerance, β-casein and lactose. Nutrients. 2015;7(9):7285-7297.
Clarkson TW, Magos L. The toxicology of mercury and its chemical compounds. Crit Rev Toxicol. 2006;36(8):609-662.
Nihart AJ, et al. Bioaccumulation of microplastics in decedent human brains. Nat Med. 2025;31:1114-1119. (detection established; harm causation emerging)
Reward pathway & stimulus excess
Kühn S, Gallinat J. Brain structure and functional connectivity associated with pornography consumption. JAMA Psychiatry. 2014;71(7):827-834.
Koepp MJ, et al. Evidence for striatal dopamine release during a video game. Nature. 1998;393:266-268.
Amen DG, et al. Discriminative properties of marijuana use on brain SPECT. J Alzheimers Dis. 2017;56(3):1037-1047.
Bratman GN, et al. Nature experience reduces rumination and subgenual prefrontal cortex activation. PNAS. 2015;112(28):8567-8572.
The stack: supplements
Avgerinos KI, et al. Effects of creatine supplementation on cognitive function: a systematic review of RCTs. Exp Gerontol. 2018;108:166-173.
Small GW, et al. Memory and brain amyloid effects of a bioavailable form of curcumin. Am J Geriatr Psychiatry. 2018;26(3):266-277.
Mori K, et al. Improving effects of Hericium erinaceus on mild cognitive impairment: a double-blind placebo-controlled trial. Phytother Res. 2009;23(3):367-372.
Kumar P, et al. GlyNAC supplementation improves glutathione, oxidative stress, mitochondrial function and cognition in older adults: a pilot trial. Clin Transl Med. 2021;11(3):e372.
Slutsky I, et al. Enhancement of learning and memory by elevating brain magnesium. Neuron. 2010;65(2):165-177.
Serhan CN, Levy BD. Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. J Clin Invest. 2018;128(7):2657-2669.
Akhondzadeh S, et al. Saffron in the treatment of mild-to-moderate Alzheimer's disease. Psychopharmacology. 2010;207(4):637-643.
Martens CR, et al. Chronic nicotinamide riboside supplementation elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9:1286.
Genetics & the contested entries
COMT (rs4680) catecholamine clearance · CYP1A2 caffeine metabolism · GSTM1-null glutathione conjugation · MTHFR methylation · ApoE risk stratification. Verify your own variants before applying genotype-specific guidance.
Pall ML. Electromagnetic fields act via VGCC activation. J Cell Mol Med. 2013;17(8):958-965. (mechanism contested in mainstream literature)
Shoemaker RC, House DE. Sick building syndrome / CIRS framework. (diagnostic framework not accepted by mainstream consensus; kept for precaution)
This guide was written by someone who rebuilt his own cognition through years of self-experimentation. That makes it lived, not proven. Treat the strongly-supported items as priorities, the contested ones as reasonable caution, introduce one change at a time, and run anything significant past a clinician who can examine you. The deciding voice on your health should be a qualified human, not a document.