Neuroprotection Nootropics
41Neuroprotective compounds defend neurons against oxidative damage, inflammation, excitotoxicity, and age-related decline. They support the brain's repair mechanisms and may slow or prevent neurodegenerative processes. Many also promote neurogenesis — the growth of new neurons.
Agmatine Sulfate
A metabolite of L-arginine produced by decarboxylation. Agmatine is an endogenous neuromodulator that acts on multiple receptor systems — it blocks NMDA receptors, activates imidazoline receptors, inhibits nitric oxide synthase, and modulates opioid signaling. This makes it useful for neuropathic pain, mood, stress resilience, and as a complement to other nootropics. Also enhances insulin sensitivity and nitric oxide production.
ALCAR
Acetyl-L-Carnitine is an acetylated form of L-Carnitine that crosses the blood-brain barrier more effectively than regular L-Carnitine. In the brain, it donates its acetyl group for acetylcholine synthesis and supports mitochondrial fatty acid oxidation for energy. Used clinically for age-related cognitive decline, depression, and diabetic neuropathy.
B-Complex
The B vitamins (B1, B2, B3, B5, B6, B9, B12) are essential coenzymes in brain energy metabolism, neurotransmitter synthesis, and methylation reactions. Deficiency in any B vitamin impairs cognitive function. B12 and folate deficiency specifically cause irreversible neurological damage if untreated. A high-quality B-complex is foundational for any nootropic regimen, particularly for vegetarians, older adults, and those under chronic stress.
Bacopa Monnieri
An Ayurvedic herb used for thousands of years as a memory enhancer. Modern research confirms it — Bacopa reliably improves memory formation, recall speed, and information retention. The catch is that benefits require 8-12 weeks of daily use to manifest; it is not an acute cognitive enhancer. The bacosides (active compounds) are also mildly sedating, making evening dosing common.
Black Seed Oil
Extracted from Nigella sativa seeds, black seed oil contains thymoquinone — a compound with potent anti-inflammatory, antioxidant, and neuroprotective properties. Used in traditional Middle Eastern medicine for over 2,000 years, modern research supports cognitive benefits through anti-neuroinflammation, acetylcholinesterase inhibition, and GABA modulation. Also supports metabolic health and immune function.
CDP-Choline
Also known as Citicoline, this is a naturally occurring compound that provides both choline and cytidine (which converts to uridine in the body). This dual action supports both acetylcholine synthesis and cell membrane repair, making it both a cognitive enhancer and a neuroprotectant. Prescribed in many countries for stroke recovery and cognitive decline.
Citicoline (CDP-Choline)
A naturally occurring intermediate in the synthesis of phosphatidylcholine, the primary phospholipid in neuronal cell membranes. Citicoline provides both choline (for acetylcholine and phospholipid synthesis) and cytidine (converted to uridine, supporting RNA and synapse formation). It is prescribed in Europe and Japan for stroke recovery and cognitive decline. Cognizin is the most studied branded form.
CoQ10
Coenzyme Q10 (ubiquinone/ubiquinol) is an essential component of the mitochondrial electron transport chain and a potent lipid-soluble antioxidant. Brain tissue has among the highest CoQ10 demands in the body due to intense mitochondrial activity. Levels decline significantly with age, and supplementation supports cellular energy production, reduces oxidative stress, and may slow neurodegenerative processes.
CoQ10 (Ubiquinol)
Coenzyme Q10 is essential for mitochondrial energy production — it shuttles electrons in the electron transport chain, the final step of ATP synthesis. Brain cells are among the most energy-demanding in the body, making them particularly sensitive to CoQ10 deficiency. Levels decline with age and are depleted by statin medications. Ubiquinol (reduced form) has much better absorption than ubiquinone (oxidized form).
Creatine
Best known as a sports supplement, creatine is increasingly recognized as one of the most effective cognitive enhancers available — particularly for vegetarians, the sleep-deprived, and older adults. It serves as a rapid energy buffer for neurons by recycling ATP, the cell's primary energy currency. The brain consumes enormous amounts of ATP, making creatine supplementation directly relevant to cognitive performance.
Emoxypine (Mexidol)
A vitamin B6 derivative with powerful antioxidant and anxiolytic properties, widely prescribed in Russia and Eastern Europe for anxiety, cognitive impairment, and cerebrovascular disease. Emoxypine inhibits lipid peroxidation, modulates GABA-A and benzodiazepine binding sites, and improves cerebral blood flow. It provides anxiolytic effects similar to benzodiazepines without sedation, tolerance, or addiction.
Forskolin
A diterpene compound from the Coleus forskohlii plant that directly activates adenylate cyclase, increasing intracellular cAMP levels. cAMP is a critical second messenger in neuronal signaling — elevated cAMP enhances long-term potentiation, supports memory consolidation, and increases the sensitivity of neurotransmitter receptors. Also used for thyroid support and body composition.
Ginkgo Biloba
One of the oldest living tree species on Earth, used in traditional Chinese medicine for millennia. Ginkgo extract (EGb 761) is one of the most prescribed herbal medicines in Europe for cognitive decline and cerebrovascular insufficiency. It improves cerebral blood flow, has antioxidant properties, and modulates neurotransmitter systems. Most effective in older adults with declining cognitive function.
Gotu Kola
Centella asiatica is an Ayurvedic and Chinese medicine herb known as the 'herb of longevity.' It has been used for centuries to enhance memory, promote wound healing, and reduce anxiety. Modern research confirms it increases BDNF, enhances collagen synthesis, improves microcirculation, and has anxiolytic effects. Unlike most adaptogens, gotu kola has clinical evidence for improving memory and attention in healthy adults.
Huperzine A
A naturally occurring alkaloid extracted from Chinese club moss (Huperzia serrata). It powerfully inhibits acetylcholinesterase — the enzyme that breaks down acetylcholine — resulting in significantly elevated acetylcholine levels in the brain. Used in Chinese medicine for centuries and now studied worldwide for Alzheimer's disease.
Huperzine A
A sesquiterpene alkaloid extracted from Chinese club moss (Huperzia serrata) that is one of the most potent natural acetylcholinesterase inhibitors known. It crosses the blood-brain barrier readily and provides longer-lasting cholinergic enhancement than most synthetic alternatives. Used in China as a drug for Alzheimer's disease and studied globally for cognitive enhancement. Particularly effective for memory formation and recall.
Lion's Mane
An edible mushroom (Hericium erinaceus) that is the only known natural compound proven to stimulate nerve growth factor (NGF) synthesis in the brain. This makes Lion's Mane uniquely valuable for neurogenesis, nerve repair, and long-term brain health. Effects build over weeks of consistent use rather than being felt acutely. Studied for cognitive decline, neuropathy, and depression.
Magnesium L-Threonate
A form of magnesium specifically designed to cross the blood-brain barrier and increase brain magnesium levels. Developed at MIT, it is the only magnesium form clinically shown to raise CSF magnesium concentrations. Brain magnesium is critical for synaptic plasticity, and deficiency (common in modern diets) impairs learning, memory, and sleep quality. Sold under the brand name Magtein.
Methylene Blue
A synthetic dye first made in 1876 that has remarkable medicinal properties. At low doses (0.5-4 mg/kg), methylene blue acts as a mitochondrial electron carrier, enhancing cellular respiration and ATP production. It is the only known compound that can donate and accept electrons in the mitochondrial electron transport chain, essentially serving as a backup energy pathway when mitochondria are stressed.
Methylene Blue
A synthetic dye with a 130+ year medical history that has recently gained attention as a mitochondrial enhancer and nootropic. At very low doses (0.5-4 mg/kg), methylene blue acts as an alternative electron carrier in the mitochondrial electron transport chain, bypassing dysfunctional complexes and directly increasing ATP production. It is the only compound known to do this. Also being studied for Alzheimer's and traumatic brain injury.
NAC
N-Acetyl Cysteine is a precursor to glutathione — the body's master antioxidant. In the brain, NAC provides potent neuroprotection against oxidative stress and also modulates glutamate signaling through the cystine-glutamate antiporter. It is used clinically for acetaminophen overdose and is studied for OCD, addiction, and neurodegenerative diseases.
NAC (N-Acetyl Cysteine)
The acetylated form of the amino acid L-cysteine and the most effective oral supplement for raising glutathione — the body's master antioxidant. NAC has an unusually broad range of evidence-based applications: it is used as a prescription drug for acetaminophen overdose, as a mucolytic, and as an adjunct treatment for OCD, addiction, and bipolar disorder. In nootropics, it protects neurons from oxidative stress and modulates glutamate.
Nicotine
Nicotine — independent of tobacco — is one of the most potent cognitive enhancers known. It enhances attention, working memory, reaction time, and fine motor skills within minutes. Research shows it is neuroprotective and may reduce the risk of Parkinson's disease. Available as gum, patches, and lozenges for non-smokers seeking cognitive benefits without any tobacco exposure.
NMN (Nicotinamide Mononucleotide)
A direct precursor to NAD+ (nicotinamide adenine dinucleotide), a coenzyme essential for cellular energy production, DNA repair, and sirtuin activation. NAD+ levels decline 50% between ages 40 and 60, contributing to age-related cognitive decline and neurodegeneration. NMN supplementation restores NAD+ levels and improves mitochondrial function, memory, and neuroplasticity in animal models.
Noopept
A synthetic peptide-derived nootropic often grouped with racetams due to similar effects, though it is technically a dipeptide analog of piracetam. Roughly 1000x more potent by weight than piracetam, requiring only 10-30 mg per dose. It provides both immediate cognitive enhancement and long-term neuroprotective benefits through BDNF and NGF upregulation.
Omega-3 (DHA)
DHA (docosahexaenoic acid) makes up approximately 40% of the polyunsaturated fatty acids in the brain and is essential for neuronal membrane structure, fluidity, and signaling. DHA deficiency is associated with cognitive decline, depression, and neuroinflammation. It is one of the few supplements with strong evidence for maintaining brain health across the lifespan.
PEA (Palmitoylethanolamide)
An endogenous fatty acid amide produced naturally in the body in response to pain and inflammation. PEA activates PPAR-alpha receptors and indirectly enhances endocannabinoid signaling without binding to cannabinoid receptors. It has strong evidence for neuropathic pain, neuroinflammation, and neuroprotection. Unlike anti-inflammatory drugs, it resolves inflammation rather than merely suppressing it.
Phosphatidylserine
A phospholipid that constitutes 15% of the brain's total phospholipid pool and is concentrated in neuronal cell membranes. Phosphatidylserine (PS) supports memory, cognitive function, and cortisol regulation. It is the only nootropic with an FDA-qualified health claim: 'consumption may reduce the risk of cognitive dysfunction in the elderly.' Particularly effective for age-related cognitive decline.
Piracetam
The original nootropic, synthesized in 1964 by Corneliu Giurgea who coined the term 'nootropic.' Piracetam modulates glutamate and acetylcholine neurotransmission to enhance memory, learning, and cognitive fluidity. Widely prescribed in Europe for cognitive decline and used globally as a cognitive enhancer. One of the most studied nootropics with decades of clinical data.
Polygala Tenuifolia
Known as Yuan Zhi in Traditional Chinese Medicine, Polygala tenuifolia has been used for thousands of years as a 'will-strengthening' and memory-enhancing herb. Modern research shows it enhances BDNF expression, inhibits acetylcholinesterase, and promotes neurogenesis. Users commonly report improved verbal fluency, dream vividness, and motivation. One of the more noticeable adaptogens with acute effects.
PQQ
Pyrroloquinoline quinone is a redox cofactor that is the only known compound that can stimulate the growth of new mitochondria (mitochondrial biogenesis) in existing cells. Since mitochondrial density and function decline with age, PQQ addresses a root cause of age-related cognitive decline. It also provides potent antioxidant protection — estimated to be 5,000x more efficient at redox cycling than vitamin C.
PQQ (Pyrroloquinoline Quinone)
A redox cofactor that stimulates mitochondrial biogenesis — the growth of new mitochondria. This is unique among supplements; most mitochondrial supports improve existing mitochondria, but PQQ actually increases their number. It activates PGC-1alpha, the master regulator of mitochondrial biogenesis, and provides potent antioxidant protection (5,000 cycles before degradation vs 4 for vitamin C).
SAMe
S-Adenosyl-L-Methionine is a naturally occurring compound involved in over 100 methylation reactions in the body. In the brain, SAMe is essential for neurotransmitter synthesis (dopamine, serotonin, norepinephrine) and myelin maintenance. Used as a prescription antidepressant in Europe and as a supplement in the US. Also supports liver function and joint health.
Sulbutiamine
A synthetic fat-soluble derivative of thiamine (vitamin B1) developed in Japan to treat chronic fatigue and asthenia. Unlike regular thiamine, sulbutiamine crosses the blood-brain barrier and significantly increases thiamine levels in the brain. It modulates dopaminergic, glutamatergic, and cholinergic systems, providing mild stimulation, improved memory, and reduced mental fatigue.
Taurine
An abundant amino acid in the brain that acts as a major inhibitory neuromodulator, antioxidant, and osmolyte (cell volume regulator). Despite its association with energy drinks, taurine is actually calming — it modulates GABA receptors and reduces neural excitability. Recent research has shown taurine supplementation reverses aging markers in multiple organ systems including the brain.
Taurine
An amino sulfonic acid (not technically an amino acid) abundant in the brain, heart, and retina. Taurine is a key neuromodulator — it activates GABA-A and glycine receptors, providing calming effects without sedation. Recent landmark research (Science, 2023) showed taurine supplementation extended healthy lifespan in animal models by improving mitochondrial function and reducing cellular senescence. It also protects neurons from excitotoxicity.
Tianeptine
An atypical antidepressant with unique nootropic properties. Unlike SSRIs which increase serotonin, tianeptine is a mu-opioid receptor agonist and enhances serotonin reuptake. It reduces stress-induced neuronal damage in the hippocampus and amygdala, improving mood, cognition, and stress resilience simultaneously. Prescription medication in many countries but carries abuse potential at high doses.
Uridine
A nucleotide base that plays a critical role in brain cell membrane synthesis, synapse formation, and dopamine receptor expression. Part of the well-known 'Mr. Happy Stack' (Uridine + Fish Oil + Choline) that synergistically supports mood and cognitive function. Uridine monophosphate is the preferred supplemental form for brain bioavailability.
Uridine Monophosphate
A nucleotide base essential for RNA synthesis and a key component of the 'Mr. Happy Stack' — uridine + omega-3 + choline. This combination promotes synaptogenesis (new synapse formation) by providing the building blocks for phosphatidylcholine in neuronal membranes. Uridine alone enhances dopamine release and supports mood. It is one of the few supplements with evidence for promoting new synapse growth in adults.
Vitamin D3
Technically a hormone, not a vitamin. Vitamin D3 (cholecalciferol) receptors are found throughout the brain, particularly in the hippocampus and prefrontal cortex. Deficiency — affecting an estimated 40-75% of adults worldwide — is associated with cognitive impairment, depression, and increased Alzheimer's risk. Supplementation is one of the most impactful interventions for people with low levels.
Zinc
An essential trace mineral concentrated in the brain's hippocampus, where it plays a critical role in synaptic transmission and memory formation. Zinc modulates NMDA and GABA receptors, supports BDNF expression, and is required for proper neurotransmitter release. Deficiency is common (estimated 17-25% of the global population) and directly impairs memory, attention, and mood.