Everyone knows what memory feels like. We use it constantly, from knowing the route home to remembering your PIN number at the ATM. But, pinning down a more precise, scientific definition has been more difficult.
A literature review in 2001 consolidated evidence available at the time that showed many molecular mechanisms in the brain which seemed to contribute to memory (1). Even though our understanding has advanced since then, we still group these functions into three separate categories:
- Acquisition describes the process of how we take information from our sensory perceptions and interpret it all to form a solid idea about what is happening to us at a given time. Our brains do this constantly, but most of these concepts will not be solidified as long term memories, being forgotten within a few seconds.
- Consolidation happens shortly afterward and involves storing these working memories on a long-term basis so they can be accessed later.
- Retrieval is the reactivation of these stored memories when they are needed. You use this process every time you access your memories.
Of course, these processes are usually firing all at once, making them hard to separate. Some of the molecular mechanisms underlying them are common to all parts of memory, making them important contributors to memory overall.
- 1 Long-Term Potentiation And Memory
- 2 Nootropics That Aid Memory
- 3 Summary
Long-Term Potentiation And Memory
One key mechanism for memory processes is long-term potentiation (LTP). Over time, neurons can add or subtract connections to their neighbors, strengthening some neural pathways, weakening others and forming new pathways altogether. This quality is called neuroplasticity, and it is the mechanism for LTP (2).
LTP is the process which stores the effects of short-term physiological processes as long-term memories by creating and modifying neural pathways. The diverse processes which interact with LTP include modification of the glutamate neurotransmitter system (3).
These processes are diverse and can be specific to certain sections of the brain. The upshot of this is that finding nootropics that can improve your memory is both a complicated task and one with a lot of potential – more targets mean more different compounds might have an effect.
For example, exercising has been proven to improve the performance of mice in the Morris water maze, a standard laboratory test for evaluating memory. Exercising aids memory by increasing the production of neurotrophins which aid in forming and reworking neural pathways. It also boosts the production of neurotransmitters like serotonin and dopamine, another mechanism that aids memory (4).
Nootropics That Aid Memory
Given the myriad of ways that memory can be supplemented on the molecular level, there are several nootropics that can safely and effectively improve your memory;.
One of the most popular nootropics available today – Piracetam – is known as a do-it-all brain booster that improves memory.
Piracetam increases the fluidity of cellular membranes, aiding a range of processes important for neuroplasticity. These include the recycling of membrane components, communication between neurons and strengthening existing neural pathways (5).
Piracetam also boosts the production of acetylcholine and glutamate, both of which are important in memory formation and recall (6).
Pinning down all the ways Piracetam aids mental function is an ongoing process. It may also increase blood flow to the brain and help neurons to use energy efficiently (7). Whatever the mechanism, Piracetam has been used as a memory enhancer for decades, and it has a proven record of efficacy according to a review of the literature (8).
Ginkgo Biloba + Panax Ginseng
A supplement formulated from the extracts of these two plants has proven effective at improving memory in healthy middle-aged volunteers. In a double-blind, placebo-controlled study of 256 volunteers, this supplement increased performance on standardized memory tests by 7.5% compared to the control group (9).
Ginkgo augments these effects by working on the acetylcholine system. This neurotransmitter has various roles in memory formation and consolidation (12).
By increasing acetylcholine’s availability to neurons, Ginkgo improved the performance of a treatment group on memory-based tasks compared to a control group in a placebo-controlled, double-blind study (13).
Often available together, these two nootropics have synergistic effects. However, they are also effective separately.
This alkaloid is extracted from a moss that has been used in traditional Chinese medicine for centuries. It works to inhibit the enzyme which breaks down acetylcholine – another way of manipulating this system to aid memory functions (14).
In a clinical trial, Huperzine-A supplements improved performance in memory tests in 58% of patients (15). It also increased performance in cognitive and behavioral measures.
As well as being a general memory enhancer, Huperzine-A or any supplement which acts on the acetylcholine system has potential as a treatment for Alzheimer’s and other diseases which affect the patient’s memory.
Not all memory-boosting nootropics work by modulating acetylcholine. Creatine works by increasing the amount of energy available to your brain cells and helping them to use it efficiently.
Creatine is used to recycle ATP, the energy currency of the cell. ATP provides energy to cells by releasing one of its three phosphate groups. Creatine can donate its own attached phosphate groups to quickly restore the ATP molecule so it may be used again (16).
Efficient energy use is especially important in the brain, the organ which has the highest energy needs in the body. So, it is especially sensitive to disruptions in its energy metabolism (16).
Creatine’s memory-boosting effects have mostly been proven in the elderly. 20g of creatine per day over one week boosted a group of 17 elderly volunteers’ performance in a range of standardized memory-based tasks in a placebo-controlled study (17).
Like many nootropics, this herbal medication was in use as a traditional medicine centuries ago. It has been used in Indian Ayurvedic medicine to aid memory, treat anxiety and improve mood (18).
It does this primarily by interacting with the acetylcholine system (18), but it also has antioxidant activities in the prefrontal cortex and hippocampus as shown in studies using rats. These areas of the brain are key for memory formation, processing, and recall (19).
A study of 76 volunteers aged between 40 and 65 showed significant increases in memory ability when given Bacopa monnieri supplements. These effects were shown to last in the long term, as the cohort who were given the supplements also scored better on the same memory tests three months later (20).
A powerful and popular nootropic, the Lion’s Mane mushroom possesses proven benefits for your brain function. It increases the production of two neurotrophins: Brain-derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) (21).
These brain chemicals promote a process called neurogenesis – in which new neurons are created to strengthen existing neural pathways. They also help neurons to create new connections to other cells, aiding in neuroplastic behavior (22).
Neurogenesis improves cognitive functions, including memory-related functions. Extracts of this mushroom are popular in the nootropics community and should be available from most suppliers.
L-Theanine + Caffeine
Many people talk about the clear focus they achieve by drinking green tea. The drink contains a mix of two neuroactive compounds: caffeine and L-Theanine.
L-Theanine works to release neurotransmitters like serotonin and dopamine, and GABA, which may explain how it works as a cognitive enhancer (23).
It can also bind to certain types of receptors in the brain, including glutamate and NMDA receptors that function heavily in memory. Its activity on glutamate receptors, in particular, could have neuroprotective effects that resist the effects of old age and other long-term memory stressors (24).
Caffeine improves memory through its action as an adenosine antagonist. Adenosine is one of the body’s primary central nervous system depressants, and blocking its action increases the concentrations of serotonin and dopamine, in the brain (25).
Nature contains examples of this effect in action. Some flower nectars contain caffeine and honeybees show increased ability to remember their location compared to non-caffeine containing flowers (26).
These nootropics work well together, and are often formulated together in the same supplement due to their synergistic effects.
This semisynthetic compound is derived from a natural alkaloid found in the Periwinkle plant and is formulated as a pharmaceutical to aid in memory disturbance disorders (27).
A 40mg dose given to volunteers in a double-blind, placebo-controlled study produced significant improvements in memory tasks compared to the control group (28).
Like many other memory-boosting compounds, it does this by interacting with the cholinergic system. This was proven by studies in rats, in which scopolamine was used to disrupt this system and cause amnesia. Vinpocetine effectively reversed the damage, restoring memory to affected rats (29).
Tryptophan is an amino acid naturally produced by the body. If you have enough, it won’t necessarily boost your memory beyond where it is already. But, as an essential amino acid, meaning one that must be taken in the diet, it is reasonably common for people to become deficient for it.
Tryptophan deficiencies can impair memory consolidation. Tryptophan is needed in the production pathway for serotonin, an important neurotransmitter for memory functions (30).
Tryptophan deficiency is possible in vegetarians and vegans since non-meat protein sources are incomplete, meaning they can lack tryptophan. Taking supplements is a good way to prevent the negative effects of such a deficiency (31).
The acetylated form of the nutrient carnitine is manufactured by the body for various metabolic purposes unrelated to memory. It is almost surprising that evidence shows it has promise as a memory-enhancing agent when taken as an oral supplement (32).
As we age, oxidative damage from free radicals accumulates in the body, causing permanent damage. The brain is no different. The nucleic acids (DNA and RNA) in our brains accumulate this damage, which can impair our memory. Acetyl L-Carnitine can reduce the buildup through its antioxidant effects (33).
Its mode of action makes it an especially good choice as a preventative measure against memory-related diseases like Alzheimer’s. In a study of 130 Alzheimer’s patients, the group given Acetyl L-Carnitine showed slower declines in memory ability over one year (34).
In Russia and the Ukraine, Semax is an approved pharmaceutical for the treatment of a range of conditions, but it is not regulated in the United States. Despite this, many people use it as a supplement for its memory-boosting and neuroprotective effects.
From studies with rat models, we know that Semax increases the production of BDNF and NGF, neurotrophins that promote neurogenesis and neuroplasticity. It also protects neurons from damage in low oxygen conditions (35).
It also boosts enkephalin production. These neurotransmitters play roles in the processing and storage of new memories (36).
Further clinical studies are needed, but the available evidence shows that Semax benefits the brain, especially by protecting neurons from suffering damage during stressful situations (37).
Another Russian medication used unofficially as a brain-boosting supplement in the United States is Selank. Like Semax, it increases the concentration of neurotrophins like BDNF in the hippocampus (38).
It too boosts the production of enkephalins, helping to form and process new memories (39).
In fact, Selank shows a similar overall profile of effects to Semax. Its highest potential is as a protective agent for brain cells when exposed to damage, resulting in memory improvements.
Selank improved the performance of rats in memory tasks based on maze navigation in rats whose brains were artificially inhibited by blocking acetylcholine (40), and for a cohort of rats with learning deficiencies (41).
Citicoline is a choline donor. This means that it can easily give a molecule of choline to another molecule as a part of a synthetic pathway to produce products the body needs.
Choline is needed to make acetylcholine, the neurotransmitter heavily involved in memory processes. It’s also a component of the cell membranes that surround all neurons. An adequate supply of choline donors protects neurons from degradation and enhances neuroplasticity (42).
In a study of 95 elderly volunteers, those who showed signs of age-related memory decline were supplemented with 1-2g of citicoline per day. At 30, 60, and 90 days, their performances on the same memory tests had significantly improved (43).
A wide spectrum of benefits is provided by the roots of a plant native to Russia and Scandinavia: Rhodiola rosea. It stimulates the central nervous system and increases neurotransmitter levels in the brain, resulting in mood improvements, increased energy, and memory-enhancing effects (44).
At least part of its effects on memory can be put down to its inhibitory effects on acetylcholine esterase – the enzyme which breaks down acetylcholine in the synaptic cleft. By slowing this process down, this neurotransmitter sticks around longer in the synaptic cleft, effectively boosting its function (45).
Some evidence supports the use of this extract as a general memory enhancer. A single dose of 0.10 mL immediately improved rats’ performances on a maze-based memory test (46).
Butyrate is an inhibitor of an enzyme called histone deacetylase, or HDAC. Histones are proteins that our DNA is wrapped around for storage, and acetyl groups are chemical blockers that can be added or removed from histones to regulate gene expression.
Neurotrophin genes are among those regulated by histone acetylation. Sure enough, butyrate supplementation is shown to boost the production of BDNF and NGF through its inhibition of HDAC (47).
It also has other downstream effects. It effectively promotes the growth of new brain cells and enhances neurons’ ability to connect to their neighbors (48).
So, what effects can you expect from taking butyrate supplements? By enhancing Long-Term Potentiation, butyrate aids the formation of long-term memories. This gives it great potential as a study aid, or as a general memory enhancer for all contexts (49).
Another natural compound found in the brain, Alpha-GPC is a natural regulator of the cholinergic system. Taking it as a supplement boosts your brain’s levels of acetylcholine and growth hormone. Acetylcholine has well-established roles in memory functions, while growth hormone facilitates the growth of new neurons (50).
In mice, Alpha-GPC improved performance across a range of standardized memory and cognition tests when compared to a control group who took no supplements. These effects were similar in nature to those observed when giving other choline-modifying compounds like citicoline (51).
There is already a large body of evidence supporting Modafinil’s effects in human volunteers. In a study of 60 healthy volunteers, both 100mg and 200mg single doses of Modafinil improved performances in memory-based and cognitive tests compared to the placebo group (53).
This effect was supported by another study with a similar design, albeit with a smaller test group (54).
The basis of its action is most likely its modulatory effects on a range of neurotransmitters associated with memory and cognition in the brain. These include serotonin, dopamine, and glutamate (55).
It’s plain to see that there is a wealth of nootropics to choose from to enhance memory. Keep in mind that these supplements work best when partnered with a healthy lifestyle. The same mechanisms that nootropics work by – boosting neurotransmitter levels, protecting brain cells from degradation and promoting neurogenesis – are all affected by regular exercise and a healthy diet too.
When you combine supplements and good lifestyle choices, you can give yourself an edge. You’ll improve your working memory for everyday applications while also protecting your brain health in the long term, preserving your neural function against the deleterious effects of old age and neurodegenerative diseases.
Philip Ghezelbash is passionate about nootropics and presenting complex science in an easy to digest manner. As an ex-personal trainer, science graduate, best-selling author, and freelance writer, Philip has helped educate millions of curious people around the world about science-based health, nutrition, and fitness.