Your memory may decline with age and high-stress lifestyle. In this post, we cover supplements and nootropics that help improve memory, with the mechanisms.
Nootropics That Improve Your Memory
1) Panax Ginseng + Gingko Biloba
Panax Ginseng is a traditional Chinese herb that improves long-term memory.
One study found the ginkgo/ginseng combination to improve memory in healthy adults .
How Panax Ginseng May Improve Memory:
- Reduces oxidative stress by promoting the release of Nitric Oxide (NO), which protects the brain 
- Increases serotonin 
- Increases neurotransmitters (dopamine, epinephrine, and norepinephrine) involved in learning in normal rat brains 
How Ginkgo May Improve Memory:
- Increases acetylcholine, which helps with learning, attention, and memory [4, 5]
- Increases antioxidant enzymes (SOD and catalase) in rat hippocampus 
- Protects the mitochondrial membrane and prevents cytochrome c release, preventing the neurons from self-destruction 
- Protects against amyloid-beta-induced toxicity, which is one of the most important factors in the development of Alzheimer’s disease 
2) Bacopa Monnieri
- Continuity of quality memory 
- Memory and cognitive function based on listening and Stroop task 
- Free memory recall 
- Delayed word call 
- Memory acquisition and retention in older men 
- Decrease rate of newly acquired information forgetfulness 
How Bacopa May Improve Memory:
- Increases acetylcholine (by acetylcholinesterase inhibition and/or choline acetyltransferase activation) and glutamate, which play a large role in learning and memory [13, 5]
- Increases enzymes and transporters that increase serotonin (TPH2, SERT), which is involved in learning and memory enhancement 
- Increases antioxidant enzymes (SOD, catalase, GPx, GSR) and glutathione, protecting the brain from oxidative stress 
- Increases brain blood flow by increasing nitric oxide (NO) production and inhibiting calcium fluctuations. This is vital to memory and brain health 
3) Huperzine A
Parkinson’s and Alzheimer’s disease patients experience degeneration in a region of the brain (nucleus basalis). In an animal model, Huperzine A restored healthy brain electrical activity (EEG). In animals suffering from lesions in this brain region, Huperzine A reduced the decay in cognitive and memory functions caused by the lesions .
Huperzine A enhanced the memory and learning of junior middle school students complaining of memory problems .
Huperzine A holds multiple neuroprotective effects .
How Huperzine A May Improve Memory:
- Increasing acetylcholine by inhibiting acetylcholinesterase .
- Increasing levels of NGF, BDNF, and TGF-Beta. These protect the brain and improve memory and learning ability .
In mice with reduced blood flow to the brain (chronic cerebral hypoperfusion), Huperzine A treatment reduced cognitive impairment by :
- reducing myelin damage
- decreasing inflammation and white matter lesions
- reducing cell death
- improving learning and memory 
- reducing inflammation (TNF-alpha)
- reducing the negative effects of low oxygen, significantly improving cognitive impairment
- Protects against low oxygen (in rats). It promotes neuron survival when the tissue is not receiving enough oxygen .
- Increases selective attention and memory storage .
- Influences the formation of new memories and learning processes .
- Increases selective attention at the moment of receiving information, strengthening and promoting learning abilities .
- Improves memory and attention in healthy men under extreme conditions .
How Semax Improves Memory:
- Increases enkephalins (a natural opiate neurotransmitter), which helps with memory formation, consolidation, and reactivation [23, 24].
- Enhances calcium ion accumulation inside the cells, which helps fight against brain degenerative processes .
- Enhances the production of proteins (immunoglobulin) that protect the brain .
Selank improved memory and brain function in rats with lowered learning abilities. Rats also optimized memory under conditions of high emotional stress .
In rats, injecting 300 μg/kg of Selank increased memory trace stability for one month .
Selank (300 μg/kg) restored cognitive function (memory, learning, and attention to sensory stimuli) in rats with chronic artificial inhibition of the brain (cerebral catecholaminergic system) .
How Selank Improves Memory:
- Activates dopamine D5 receptor (DRD5), which plays a key role in the formation of memory and learning processes .
- Increases BDNF in the hippocampus of rats .
- Increases enkephalins, which plays a role in memory formation, consolidation, and reactivation [23, 24].
Sodium butyrate increases long-term memory by increasing synaptic activity in the hippocampus long-term .
Sodium butyrate also increased memory function in patients with age-related brain diseases .
Moreover, sodium butyrate prevents memory impairment in experimental pneumococcal meningitis .
How Butyrate May Improve Memory:
Creatine‘s main role is recycling energy (ATP), primarily in the brain and muscles.
Creatine is currently in Phase III clinical trials for the treatment of Huntington’s disease .
In elderly patients, creatine supplementation improved cognition and memory in all but one tests, showing that creatine can aid cognitive function in the elderly .
How Creatine Improves Memory:
- Creatine is stored as phosphocreatine, which acts as a high-energy reserve. Phosphocreatine decreases rapidly during brain activity. Supplementing with creatine (2 grams per day for 1 month) increased average brain creatine by 9.7%. It acts as an energy source for the brain to focus on learning tasks, as well as an energy source for storing memories.
- Protects against beta-amyloid toxicity in the hippocampus 
- Protects neurons by maintaining mitochondrial energy production and protecting the mitochondria (by increasing mitochondrial membrane potential, reducing intra-mitochondrial levels of reactive oxygen species, and reducing calcium inside the mitochondria) .
Studies Show Glucose:
- Improved cognitive functions in subjects with different neurodegenerative diseases [41, 42]
- Enhanced learning and memory in healthy young animals and humans 
- Improved verbal memory associated with conditions 
- Glucose levels are lowered following cognitively demanding tasks, supplementing may restore positive effects 
- Significantly improved memory and attention in college students
Impaired blood sugar regulation is linked to cognitive impairments, especially visual memory. This impairment is worse in older individuals .
How Glucose Improves Memory:
- Improves memory consolidation and memory coding when task demand is high 
- Increases insulin levels, which is linked to memory enhancement 
- Increase acetylcholine, which is critical in memory and learning processes 
- Glucose-sensitive neurons in the brain may serve as glucose sensors. Therefore, glucose may induce neural changes that improve memory 
- Prevents cell death 
Benefits for the Brain
- Protects against stress-induced impairment of brain development in rats .
- In older people, long-term supplementation with curcumin significantly improved working memory .
- Prevents learning and memory deficits in rats (treated with Sodium Metabisulfite) .
Helps with Alzheimer’s Disease
- It protects against neuronal self-destruction in rats, thus, improving learning and memory abilities .
- It reduces amyloid-induced spatial memory impairment in rats .
How Curcumin Improves Memory:
- increasing BDNF, CREB, and synapsin I
- reducing oxidative stress
- increasing synaptic plasticity
- protecting against chronic stress
- protecting against glutamate over-excitation
- restoring glutathione levels and insulin receptors 
- inhibiting inflammatory cytokines 
10) Citicoline (CDP-Choline)
- Improve memory and learning, including situations of impoverished environments (animals) [55, 56].
- Improve cognitive control (a frontal lobe function) in humans .
- Reduce memory impairments associated with brain diseases (chronic cerebrovascular disease, dementia, cerebral insufficiency, memory problems, dementia, and ischemic stroke) [58, 59, 60].
How Citicoline Improves Memory:
- Enhances membrane phosphatide synthesis .
- Decrease neuronal self-destruction .
- Increases glutathione, while decreasing oxidized glutathione .
11) Alpha-GPC Improves Memory
In mice, alpha-GPC improved a wide number of memory functions (working memory, verbal memory learning, and maze pathway learning) .
In amnesia-induced rats, alpha-GPC improved learning and memory .
How Alpha-GPC Improves Memory:
Although it is addictive, nicotine is one of the most well-documented drugs to improve memory.
Rather than smoking, there are safer ways to consume it, such as gum, snus, patches, or vaporizing.
Cognitive Benefits of Nicotine
- Makes it easier to consolidate memories in perceptual learning 
- Improves learning tasks (including contextual conditioning) 
- May protect the brain 
- Improves attention 
- Improves dexterity/coordination 
- Reduces cognitive impairment 
- Improves short-term memory 
Nicotine patches successfully helped with cognitive impairment in Alzheimer’s disease, schizophrenia, and ADD/ADHD . Nicotine may be a promising treatment for Parkinson’s disease, Down’s syndrome, and age-related memory impairment [70, 71].
How Nicotine Improves Memory (Mechanisms)
- Increases acetylcholine activity [72, 73]
- Activates the alpha-4 beta-2 nicotinic receptor, implicated in learning 
- Activates the alpha-7 nicotinic receptor, implicated in long-term memory 
- MAO-A (dopamine, serotonin, melatonin, epinephrine, norepinephrine, tyramine)
- MAO-B (phenylethylamine, dopamine, and other amines)
Studies show selegiline:
- Helped memory impairments associated with Alzheimer’s 
- Improved memory/intelligence in Parkinson’s patients vs placebo 
- Improved memory impairments by the cholinergic system associated with dementia 
- Improved long-term memory in aged mice (0.25 mg/kg 3 times a week) 
- Protected against memory impairments from iron in mice 
How Selegiline Improves Memory:
- Prevents prolongation of P300 latency [75, 79, 80]
- Increases dopamine (through inhibiting MAO-B) [81, 82]
- Acts as an antioxidant and protects against glutamate toxicity 
- Inhibits acetylcholinesterase and thus increases acetylcholine [83, 84]
Adult ADD/ADHD patients given modafinil (200 mg/day) showed significant improvements in short-term memory, visual memory, and spatial planning. However, although they responded more accurately on tests, they had slower response .
Modafinil improves working memory in methamphetamine-impaired individuals .
How Modafinil Improves Memory:
- Increases glutamate in the thalamus 
- Prevents glutamate toxicity 
- Increases dopamine, norepinephrine (inhibits dopamine/norepinephrine transporter) and serotonin 
- Increases histamine neurons in multiple parts of the brain 
Racetams, Research Chemicals and Memory
Piracetam improved long-term/short-term memory retrieval in 60 dyslexic boys .
Piracetam displayed a significant improvement in verbal and nonverbal short-term memory and attention in patients undergoing bypass surgery .
How Piracetam Improves Memory:
- Increase the function of muscarinic choline receptors .
- Increases NMDA receptors .
- Improves cell membrane fluidity .
- Enhances the brain’s ability to use glucose.
In Alzheimer’s or multi-infarct dementia patients, 800 mg oxiracetam twice daily improved memory, with no signs of tolerance. However, some cognitive tests were statistically worse than baseline after late-stage follow-up .
In humans, oxiracetam shows greater improvement in memory factors compared to piracetam . In rats and mice, oxiracetam improved memory as well as piracetam. In addition, it also improved learning ability .
In rats, oxiracetam decreased brain injury, and increase the ability of learning, memory, and space cognition rats with traumatic brain injury .
How Oxiracetam Improves Memory:
- Prevents the decrease of acetylcholine in the brain, critical in improving and restoring memory .
17) Coluracetam (BCI-540/Mkc-231)
In rats with brain damage from chemicals, coluracetam reduced the memory impairments with no significant side effects .
Coluracetam also displayed long-lasting (72 hours after the last dose) cognitive function improvement after repeated administration .
How Coluracetam Improves Memory:
Pramiracetam is marketed as a treatment for memory and attention deficits in aging people with brain degenerating diseases and vascular dementia.
In males with brain injuries, pramiracetam (400 mg) improved memory with no tolerance over an 18 month period. The effect was sustained even 1 month after discontinuing treatment .
In rats, pramiracetam (7.5 mg/kg and 15 mg/kg) improved long-term memory but did not significantly improve working memory .
Pramiracetam was able to partially reduce the memory impairment caused by scopolamine in both young and old (18-42 and 55-65 years) patients .
Pramiracetam has a statistically significant effect on improving the memory of patients with lack of oxygen in the brain .
How Pramiracetam Improves Memory:
- Increases nicotinic acetylcholine receptor activity .
- Increases choline uptake in rat hippocampus .
Phenylpiracetam is a Russian drug created in 1983 to combat the prolonged stress of working in space. It is a prescription drug under the name Phenotropil in Russia.
In stroke patients, phenotropil restored daily activities and brain function .
In patients with brain damage (encephalopathy), phenotropil improved brain functions, memory, and counting abilities .
In animals that lack blood flow to the brain, phenotropil retained their memory functions and vitality .
The mechanisms of phenylpiracetam/phenotropil are not clinically clear but should be similar to other drugs in the racetam family.
20) Fasoracetam (NS-105)
Fasoracetam is a racetam drug that is in clinical trials for vascular dementia and ADHD.
The mechanisms of fasoracetam are not clinically clear but should be similar to other drugs in the racetam family.
PRL-8-53 is a nootropic research chemical. Joe thought PRL-8-53 made his cognitive function worse.
In a double-blind study, PRL-8-53 enhanced learning and memory retention in humans .
The Mechanisms of PRL-8-53 are not clinically clear.
Other Ways of Protecting Memory and Avoiding Cognitive Diseases
- Stress-Management 
- Antioxidants 
- Omega-3 Fatty Acids 
- B Vitamins and Folate 
- Medium Chain Triglycerides (Axona and Coconut Oil) 
- Physical Activity 
- Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) 
- Proper Nutrition 
- Mental Exercise 
- Tea intake (Black/Oolong) 
- Statin use associated is with a decreased risk of dementia 
- Lithium may protect against dementia in bipolar patients 
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