- What Is Acetylcholine?
- Acetylcholine Receptors
- Acetylcholine and Alzheimer’s Disease
- Acetylcholine Foods and Supplements
- Roles and Effects of Acetylcholine
- Acetylcholine-Related Health Conditions
- Factors That May Influence Acetylcholine Levels
- 10 Foods to Boost Your Brain Health
- Supplements that Boost Acetylcholine
- Acetylcholine and the Racetams
- Anticholinergic Medications
- Acetylcholine Supplements – The Last Word
What Is Acetylcholine?
Diet might play a role in the production of acetylcholine and a decreased risk of certain diseases.
Acetylcholine is a neurotransmitter produced in the brain that plays an important role in muscle movements, thinking, and working memory.
Working memory is the brain’s ability to hold information in the mind temporarily.
Problems with the production and use of acetylcholine are hallmarks of diseases such as dementia and myasthenia gravis (an autoimmune disease that weakens the muscles).
Acetylcholine receptors are proteins to which acetylcholine binds, allowing signals to flow from one nerve cell to another.
Drugs that work on the acetylcholine receptors have many medical uses, including the treatment of Alzheimer’s disease and myasthenia gravis.
Medications that stimulate acetylcholine receptors are called agonists, while those that inhibit receptors are called antagonists.
Acetylcholine and Alzheimer’s Disease
People with Alzheimer’s disease produce less acetylcholine.
Medications that stop the breakdown of acetylcholine in the brain, called cholinesterase inhibitors, may be prescribed to people with mild to moderate Alzheimer’s symptoms.
These drugs may help delay or prevent behavioral symptoms such as agitation, delusions, or sundowning (a state of confusion and distress late in the day) from becoming worse for a limited period of time.
However, they may lose their effectiveness as the brain produces less and less acetylcholine.
Acetylcholine Foods and Supplements
There are no foods or supplements that contain the chemical acetylcholine, though some foods and supplements may contain the building blocks of acetylcholine.
Choline is an essential nutrient and a building block of acetylcholine. Foods that are naturally high in choline include whole eggs, meats and fish, and whole grains.
Studies in laboratory animals and humans suggest that consuming foods or supplements rich in choline may elevate levels of acetylcholine in the brain.
This means that choline could potentially have a protective effect against certain types of dementia, including Alzheimer’s disease.
However, more research is needed to tease out the complicated relationship between dietary choline and brain function.
Acetylcholine is a hot topic within the realm of memory enhancement. It is a neurotransmitter that is critical for the everyday functioning of the brain: particularly in the areas of movement, learning & memory, and sleep quality. Check out this post to learn how to promote balanced acetylcholine in your body and function at your very best!
Acetylcholine was first discovered in 1914, and was in fact the first of the brain’s major neurotransmitters to be identified .
Acetylcholine was first studied for its role in regulating wakefulness and sleep. However, since its initial discovery it has been associated with a wide variety of different important functions and roles throughout the brain and the rest of the body .
It is believed that choline — the chemical and metabolic precursor to acetylcholine — was originally used by single-celled organisms billions of years ago to create their protective outer cell layers (membranes). Since this earliest biological function, its role has since been expanded over the course of evolution to become involved in a wide range of important functions including muscular control, sleep regulation, and even higher cognitive functions, such as learning and memory .
Acetylcholine is synthesized from acetyl-coenzyme A (which comes from glucose) and choline, with the help of an enzyme called choline acetyltransferase . However, unlike many other neurotransmitters, acetylcholine is created (synthesized) within the connections between neurons (the neural synapses), rather than inside neurons themselves .
One of the central functions of acetylcholine is to trigger muscle movements, which it does by stimulating the synapses where the nervous system connects to the muscular system (neuromuscular junctions, or “NMJs”) .
However, this role is not just limited to controlling the muscles that move the body around: for example, acetylcholine and histamine interact together to contract muscles in the lungs, which enables breathing (respiration) .
While it plays a large and complex variety of roles throughout the brain, acetylcholine is most commonly associated with certain cognitive functions, such as memory and attention. It is also believed to play a role in promoting the phase of sleep associated with dreaming (REM sleep) .
Roles and Effects of Acetylcholine
1) Learning and Memory
Several different lines of scientific evidence suggest that acetylcholine plays a crucial role in learning and memory.
For example, acetylcholine is believed to be critically involved in the development and progression of several common neurodegenerative diseases that involve memory impairments, such as dementia and Alzheimer’s disease. In fact, some of the memory-related symptoms of these disorders appear to correlate with reduced levels and activity of acetylcholine — especially in certain brain regions known to play a key role in memory, such as the hippocampus .
For this reason, drugs that increase acetylcholine are commonly used by medical practitioners to treat patients with Alzheimer’s .
Scopolamine — a drug that is known to block acetylcholine activity — has been reported to impair the acquisition of new information and memories, according to several studies in both humans and animals .
In monkeys, disruption of the brain’s supply of acetylcholine — especially in the cerebral cortex and hippocampus — has been reported to impair the acquisition of factual information (during a discrimination learning task), and also reportedly produces memory impairments comparable to human amnesia .
Although the precise mechanisms involved in acetylcholine’s effects on memory are complex and not yet fully-understood, some researchers believe that it plays a central role in synaptic plasticity, the biological mechanism which allows neurons to store new information and memories by modifying the way they connect to each other .
Due to its potential role in stimulating learning and memory, some researchers have investigated whether using dietary supplements or other compounds to increase acetylcholine levels might influence cognitive functioning.
Although this research is in a relatively early stage, some studies have reported some interesting preliminary findings. For example, according to one observational study in almost 1,400 people, higher dietary intake of choline was associated with slightly better cognitive performance (especially verbal and visual memory) .
Relatedly, one small-scale trial in 24 healthy male volunteers reported that supplementation with 500-1,000mg of CDP-choline may have improved a variety of cognitive processes (including working memory and verbal memory). However, this effect was only observed in people whose normal (“baseline”) cognitive performance was already relatively below-average. By contrast, people with “average” levels of cognitive performance showed no effects from choline supplementation, while high-performing subjects actually got worse !
Based on these initial findings, it is likely that acetylcholine has an important role to play in cognition, learning and memory — although the conflicting evidence suggests that its role is complex, and is not as simple as “more acetylcholine = better”!
2) Controlling the Sleep-Wake Cycle
When acetylcholine was first discovered, it was being studied primarily for its role in the regulation of the sleep-wake cycle . Today, acetylcholine is still one of the main neurotransmitters believed to be responsible for stimulating wakefulness (along with other important neurotransmitters and hormones, such as orexin, histamine, norepinephrine, and dopamine) .
For example, some studies have reported that the activity of acetylcholine neurons is significantly increased during waking, whereas the activity of these same neurons is suppressed during certain stages of sleep (such as slow-wave sleep, or SWS) .
Some researchers have proposed that the wakefulness-promoting effects of acetylcholine may be involved in the “stimulating” effects of certain drugs that increase the activity this neurotransmitter, such as amphetamines and other stimulant drugs like modafinil and cocaine. Conversely, the effects of sleep-promoting (“sedative/hypnotic”) drugs, such as zolpidem (Ambien) and various antihistamines, may partially come from their ability to reduce acetylcholine activity .
Relatedly, animal studies in rats have reported that the sedative/hypnotic drugs zolpidem (Ambien), diazepam, and eszopiclone may induce their effects by stimulating GABA receptors that (in turn) suppress acetylcholine release by the brainstem .
Acetylcholine’s role in sleep- and wakefulness-related behaviors may also tie into its role in learning and memory. For example, while acetylcholine activity is generally suppressed during many stages of sleep, acetylcholine levels have been reported to increase during REM sleep — one of the most important stages of sleep for storing (“consolidating”) new memories .
3) Attention and Alertness
Historically, acetylcholine has been thought to be mainly important in learning and short-term memory functions. However, more recent studies have provided support for acetylcholine’s role in attention and alertness .
For example, one animal study reported that acetylcholine levels in the brain increased significantly when rats were placed into an environment that required high degrees of sustained attention (high attentional effort). Furthermore, increasing the difficulty of the attention task (by adding distracting stimuli) further increased acetylcholine levels. Based on these findings, the authors of this study concluded that acetylcholine may play a direct role in stimulating attention and focus .
Relatedly, one study of 60 healthy adult women aged 40-60 reported improvements in attention after 28 days of supplementation with CDP-choline, a compound that is believed to increase acetylcholine levels throughout the brain .
While these early results are promising, much more research will be needed to confirm whether acetylcholine supplementation can consistently influence memory abilities in healthy human users.
Acetylcholine is also believed to be involved in inflammation. In fact, its influence on inflammation is so significant that it even has a biological pathway named after it, called the “cholinergic anti-inflammatory pathway” .
Pro-inflammatory cytokines are produced by cells of the immune system in response to injury or infection. These cytokines, in turn, initiate a chain of effects that recruit a variety of inflammatory cells to the site of infection in order to contain it.
The cholinergic anti-inflammatory pathway is currently believed to provide a sort of “braking” effect on this immune response. This may protect the body against the tissue damage that can occur if an acute inflammatory response spreads beyond the local tissues to affect the kidney, liver, lungs, or other major organs .
For example, according to one animal study, increased acetylcholine levels were associated with reduced inflammation in the intestinal gut mucosa — possibly due to the activation of alpha-7 nicotinic acetylcholine receptors (α7nAChRs), which inhibit the release of pro-inflammatory cytokines .
Relatedly, according to studies of inflammation-related health conditions (such as IBD), acetylcholine has also been reported to reduce the levels of other pro-inflammatory cytokines, such as IL-6, IL1B, and TNF-a .
Additionally, specific sub-types of acetylcholine receptors — such as alpha-7 nicotinic acetylcholine receptors, or “α7nAChRs” for short — have been reportedly found on a number of different immune system cell types, including macrophages, monocytes, and mast cells. Some researchers have proposed that acetylcholine may reduce inflammation by inhibiting these immune cells .
Other systems involved in anti-inflammatory mechanisms, such as vagus nerve stimulation, are also believed to be activated by acetylcholine . Decreased vagus nerve activity has been reported in studies of inflammatory bowel disease (IBD), and may in part result from reduced anti-inflammatory stimulation from acetylcholine .
However, the precise role of acetylcholine in overall inflammation is not fully clear, and is probably more complex than some of the above findings may suggest. For example, some studies have reported that acetylcholine (again acting via nAChRs) also suppresses the production of antiinflammatory cytokines, such as IL-10. Therefore, more research will still be needed to understand exactly how acetylcholine either increases or decreases the inflammatory response in different contexts.
5) Protecting Against Infections
In addition to its role in inflammation, some preliminary evidence from animal research suggests that acetylcholine may have important interactions with the immune system, and may play a role in how it responds to infections.
For example, one animal study has reported that acetylcholine may inhibit the formation of “biofilms” during certain kinds of infections (such as fungal infections caused by Candida albicans) .
6) Helping Gut Movement
Another important function of acetylcholine is to facilitate the movement of food through the gastrointestinal tract (a process called peristalsis).
More specifically, this function is associated with acetylcholine activity within the “parasympathetic” nervous system — the part of the nervous system that is associated with the “rest-and-digest” functions (which are the counterpart to the “fight-or-flight” responses caused by the sympathetic nervous system) .
Specific types of acetylcholine receptor, called nicotinic acetylcholine receptors (nAChRs), are believed to be particularly involved in this process. These receptors get their name from the fact that they are stimulated by nicotine: and the involvement of nicotine in stimulating these receptors is believed to be why up to 1 in 6 people who quit smoking report (temporary) gastrointestinal symptoms, such as constipation. The idea behind this is that because a chronic smoker’s gastrointestinal acetylcholine system is “used” to getting more nicotine-based stimulation from tobacco, it may become less able to function properly once this extra source of stimulation is removed, thereby resulting in impaired digestive processes (such as constipation symptoms) .
Additionally, some antidepressant drugs (monoamine reuptake inhibitors) that are able to inhibit these nicotinic acetylcholine receptors have been commonly reported to cause constipation as a potential side-effect. Some such antidepressant medications include :
7) Reducing Pain
Some evidence also suggests that acetylcholine may also be involved in mediating the perception of pain, and that targeting this system may potentially help treat pain.
For example, some research has reported that the Alzheimer’s disease medication donepezil — which primarily acts by increasing acetylcholine levels — produces a dose-dependent pain-relieving effect in human patients, and may also have some efficacy as a preventative treatment for the symptoms of migraines .
Relatedly, a systematic review of multiple cell- and animal-based studies concluded that higher levels of acetylcholine in the spinal cord are generally associated with pain relief, whereas reducing acetylcholine activity (such as by blocking its receptors) often results in increased sensitivity to pain .
Although the exact mechanisms behind these potential effects are not fully understood yet, early evidence from various studies in both humans and animals suggests that nicotinic and muscarinic types of acetylcholine receptors are each likely involved in these potential pain-related effects .
8) Improving Blood Flow
According to some early cell-based studies, acetylcholine may play a role in regulating blood circulation — specifically, by stimulating the production of nitric oxide, a compound that controls blood pressure by relaxing the blood vessels (vasodilation) throughout the cardiovascular system .
Some preliminary findings also suggest that muscarinic acetylcholine receptors, in particular, may be especially relevant to the potential cardiovascular functions of acetylcholine .
9) Hormone Balance
Finally, some research also suggests that acetylcholine activity has an influence on the production or secretion of various hormones throughout the body and brain.
For example, some studies have reported that acetylcholine levels are correlated with the secretion of hormones such as prolactin and growth hormone from the pituitary gland. Although the full mechanisms are not known yet, some researchers believe that a significant amount of acetylcholine’s effects on hormones may come from its ability to influence neural activity in the hypothalamus, a brain region that is widely believed to be heavily involved in hormone regulation .
Acetylcholine-Related Health Conditions
Due to its wide range of roles throughout the body and brain, acetylcholine has been implicated in the development, progression, or symptoms of a variety of health conditions.
Although serotonin is the neurotransmitter most commonly associated with depression and other mood disorders, other major neurotransmitters — including acetylcholine — may also play important roles in these psychiatric conditions.
Although the exact role of acetylcholine in depression is not yet fully-understood, a handful of preliminary animal studies have reported that drugs which block nicotinic acetylcholine receptors (nAChRs) — such as mecamylamine — appear to have “antidepressant-like” effects in rodents .
Building on this, according to two early phase-II clinical trials in humans with treatment-resistant depression (TRD), mecamylamine was reported to alleviate some depression symptoms when used in combination with more traditional antidepressants (such as selective serotonin reuptake inhibitors, or SSRIs) .
Nonetheless, while acetylcholine may play some role in depression, it is likely to be only one piece of a much larger and more complex puzzle. In the meantime, most scientific research on the development and treatment of depression will likely continue to focus primarily on the role of other neurotransmitters, such as serotonin, which have relatively much more research behind their role in depression and mood disorders.
Smoking And Depression
Interestingly, some of the preliminary findings described above may account for some of the widespread associations that many studies have reported between smoking and depression .
Specifically, some researchers have proposed that short-term (acute) nicotine exposure can result in a reduction (“down-regulation”) of acetylcholine receptors . This may initially produce an “antidepressant” or “anti-anxiety” effect in relatively new smokers, which could in turn contribute to the development of an addiction to (or dependence on) nicotine.
However, chronic exposure to nicotine may eventually cause nicotinic acetylcholine receptors to actually increase in number, which would reverse these initial effects. Therefore, smoking may actually lead to increased negative moods and anxiety in the long term .
These adverse long-term effects, then, could potentially explain why rates of depression and other mood disorders tend to be higher in people who smoke .
2) Alzheimer’s Disease
Acetylcholine has also been proposed to play a potentially-significant role in the development or symptoms of certain common neurodegenerative diseases, including Alzheimer’s disease and various other forms of dementia .
In Alzheimer’s disease, the so-called “cholinergic” neurons — the brain cells that primarily use acetylcholine — gradually become damaged and destroyed. Additionally, important molecules called acetylcholine transporters may also become impaired as the disease progresses. These molecules are responsible for transporting acetylcholine into neurons: and impairing them can therefore make it more difficult for acetylcholine to fulfill its normal functions throughout the brain. Together, then, these two important acetylcholine-related mechanisms are likely to contribute significantly to some of the hallmark cognitive symptoms of these disorders .
Many (though not all) drugs that are currently used to treat Alzheimer’s disease are acetylcholinesterase inhibitors. As their name suggests, these drugs inhibit the enzyme acetylcholinesterase, which is responsible for breaking down the neurotransmitter acetylcholine throughout the brain. Therefore, inhibiting these enzymes can result in an overall increase of acetylcholine levels and activity, which may potentially compensate for the loss of cholinergic neurons that typically occurs in Alzheimer’s disease .
For example, two common Alzheimer’s medications, galantamine and donepezil, are each acetylcholinesterase inhibitors — and their therapeutic effects in relieving some of the cognitive symptoms of Alzheimer’s are believed to stem primarily from to their ability to stimulate acetylcholine activity throughout the brain .
However, not all Alzheimer’s medications target acetylcholine. For example, the widely-used Alzheimer’s drug memantine targets other mechanisms entirely (specifically, NMDA receptors).
Therefore, acetylcholine is probably only one piece of a much more complex puzzle. Nonetheless, it does appear to play an important role in at least some of the main mechanisms and symptoms of Alzheimer’s disease — and more research will be needed to explore these mechanisms more fully, as well as to potentially develop future medical treatments for these neurodegenerative disorders.
Factors That May Influence Acetylcholine Levels
Many biological processes and pathways are involved in determining the total amount of acetylcholine in the body and brain, as well as its overall degree of activity.
This means that there are many different mechanisms and pathways that can influence acetylcholine, such as:
- Increasing or decreasing the levels of its “ingredients” (metabolic precursors), such as choline
- Activating or inhibiting the enzymes that produce (synthesize) active acetylcholine from its precursors, such as choline acetyltransferase or acetyl-coenzyme A
- Stimulating or suppressing the release of acetylcholine by nervous system cells
- Directly activating acetylcholine receptors, such as by “imitating” natural (“endogenous”) acetylcholine
- Blocking acetylcholine receptors, thereby preventing them from being activated by natural acetylcholine
- Increasing or decreasing the number of acetylcholine receptors
Why Target The Acetylcholine System?
Because acetylcholine is believed to be involved in the development of a variety of diseases and other health conditions, there are many potential uses that have been proposed for substances that can target the acetylcholine system.
Additionally, many people in the “nootropics” community believe that certain compounds and supplements that target this system may have certain “cognitive benefits.” While the evidence for these compounds having significant effects on cognition in healthy human users is currently relatively weak, this is another common reason that people are sometimes interested in finding out more about substances and compounds that can affect this important neurotransmitter system.
In any case, If you believe you have a health condition or other reason to try to influence your acetylcholine levels, it is extremely important to always talk to your doctor about any new supplements or dietary changes you make. This is because these approaches could have negative interactions with any other drugs you are taking, other pre-existing health conditions, and other health-related factors. None of the information in this post should ever be used to replace conventional medical treatment.
It is also important to keep in mind that many of the compounds and substances discussed below have only been tested in animal- or cell-based studies. This means that their effects and overall safety in healthy human users is not known.
Therefore, these compounds should be considered as currently having “insufficient evidence” for any specific use — and much more research will be needed to verify what effects they may have in humans, as well as how safe they may be.
Factors That May Increase Acetylcholine
A large number of different supplements, dietary compounds, and other factors have been proposed to play a role in increasing acetylcholine levels and activity throughout the brain. Once again, because the acetylcholine system is highly complex, there are several different mechanisms and pathways that can be targeted to achieve these effects.
For example, one relatively common approach to increasing acetylcholine levels is to supplement with choline, one of the most important “ingredients” that the nervous system requires in order to produce the active neurotransmitter acetylcholine .
Choline can be acquired naturally through the diet, and is found in a variety of common foods such as eggs and liver . There are also several types of supplements that are based on choline, such as citicoline / CDP-choline and alpha-GPC .
Alternatively, another common way to increase acetylcholine levels is to inhibit acetylcholine esterase (AChE), the enzyme responsible for breaking this neurotransmitter down throughout the brain. Many herbs and other natural plant compounds fall into this category of mechanisms, such as rosemary, huperzine A, bacopa monnieri, and ginkgo biloba .
Other factors, such as hormone levels, may have a less direct — but still potentially significant — effect on acetylcholine activity. For example, some serotonin neurons are believed to be involved in stimulating the release of acetylcholine. According to one animal study, rats whose levels of estrogen were experimentally increased were reported to show a significantly greater release of acetylcholine in response to serotonin activity, suggesting that estrogen might be playing an indirect role in “setting” the sensitivity of the acetylcholine system to other forms of stimulation .
All in all, a large variety of dietary compounds and supplements have been reported to potentially increase the levels of and activity of acetylcholine throughout the brain, and each one may act through one or more of the above mechanisms and pathways. A more comprehensive list of such potential compounds includes:
Once again, it is important to keep in mind that many of the above compounds have only been tested in animal- or cell-based studies, and their effects and overall safety in healthy human users is not fully known. Therefore, we don’t recommend casually experimenting with any of these compounds — especially not without talking to your doctor first!
Factors That May Decrease Acetylcholine
There are also many compounds and drugs that may decrease acetylcholine levels, or reduce its activity.
In general, drugs or other compounds that reduce acetylcholine levels — or otherwise inhibit its activity — are commonly known as “anticholinergics.” (To learn more about these substances and how they work, we recommend checking out our detailed SelfDecode posts on anticholinergics, which you can find here and here.)
Once again, these drugs may exert this effect by targeting one or more of the multiple different potential mechanisms and pathways related to the creation or release of acetylcholine.
Some of the supplements, dietary compounds, and drugs that have been proposed to have some potential anticholinergic effects and mechanisms include:
10 Foods to Boost Your Brain Health
There’s a lot of power in food. It has the ability to make you feel great or terrible, and holds influence over your weight, energy and overall health.
Certain foods are good for organ function and vitality, including your brain. You want to do anything you can to nurture your cognitive abilities, and food is one of the easiest — and most delicious — ways to do just that.
Here are some of the best foods to boost your brain health.
According to a study from Tufts University, blueberries are not only one of the best foods for your brain, but these delicious little fruits can actually improve memory and reverse memory loss. The flavonoids found in blueberries interact with nerve cells, increasing communication among them and stimulating the regeneration of brain cells.
Fish is known for containing omega-3 fats, which help to fight inflammation throughout the body, including the brain. The omega-3 fats EPA and DHA are the most effective and occur naturally in fish. Low DHA levels have been linked to a higher risk of Alzheimer’s disease, while proper levels of EPA and DHA help produce serotonin.
Broccoli is a great source of vitamin K, which has been known to boost cognitive function and brainpower. Research also suggests that the glucosinolates in broccoli help slow the breakdown of the neurotransmitter acetylcholine. Low levels of acetylcholine have been linked to Alzheimer’s disease.
Nuts are rich in vitamin E, which has been known to prevent cognitive decline. Almonds and walnuts are two great sources of vitamin E. Research has suggested walnut consumption may support brain health by increasing inferential reasoning.
5. Olive Oil
Olive oil is high in antioxidants called polyphenols, which aid in reversing memory deficits due to aging. It is also rich in monounsaturated fats, which increase levels of acetylcholine, the brain chemical attributed to memory and learning. Monounsaturated fats can reduce the risk of Alzheimer’s by up to 40 percent.
This nutrient-rich vegetable contains vitamin K and manganese, both known for boosting brain function. Manganese also helps with your brain’s ability to focus on tasks and can be used as a pick-me-up.
Avocado is high in monounsaturated fats that protect brain cells and promote blood flow, which helps increase brain function. It also contains folate, which is essential for brain health and nurtures cognitive function, particularly memory.
This leafy green has many health benefits, including being a brain booster. Studies suggest spinach protects the brain from cognitive decline. Containing folate and beta-carotene, an antioxidant that works to fight heart disease and cancer, spinach is a nutritious and delicious way to improve cognitive function.
9. Pumpkin seeds
Pumpkin seeds are rich in zinc, a mineral that supports brain function by helping to prevent neurodegeneration and the development of Alzheimer’s. It also contains omega-3 and omega-6, which improve mental health, memory and brain development.
Eggs are high in choline, an essential nutrient for healthy brain function. Choline maintains cell membrane structure and is a key element in manufacturing neurotransmitters for brain cell communication.
So there you have it—the top foods for brain health that can improve your memory, overall brain function and prevent cognitive disease later in life. Being healthy is a conscious effort, but in this case, can be fun trying new, healthy recipes. For more ways to stay healthy, subscribe to our blog.
The neurotransmitter Acetylcholine (ACh) plays a leading role in alertness, focus, memory and mood. ACh also contributes to neuroplasticity that supports long-term potentiation needed to form long-term memory. And for a healthy, optimized brain.
ACh deficiency has been linked to ADHD, Alzheimer’s, dementia, Parkinson’s, and multiple sclerosis.
But you can’t take acetylcholine as a supplement. There is no such thing as “acetylcholine pills”, or “acetylcholine tablets”. But certain foods can help boost acetylcholine (ACh) by providing your brain with the choline it needs to synthesize ACh.
Food sources of choline are egg yolks, liver, milk and other dairy products, certain grains like quinoa and amaranth, bacon, edamame and cruciferous vegetables.
Most of us don’t get enough choline in our diet to produce the acetylcholine we need. And this is particularly true if you’re using any one of the racetam nootropics in your stack.
So many neurohackers use one of the choline supplements we discussed in Part 1 – Advanced Guide to Choline in Nootropic Stacks of this series to boost acetylcholine. Including:
- Alpha GPC
- Choline Bitartrate
- Choline Citrate
And from our review, we know these nootropics often do so much more than simply increase acetylcholine in our brain.
But we have several other options available to help increase ACh release in the brain, inhibit its breakdown, encourage reuptake, stimulate ACh neuroreceptors, or provide the ingredients needed to create acetylcholine.
These nootropic supplements are considered cholinergic compounds. The following list is a brief description of both natural and synthetic nootropics that help acetylcholine in your brain.
For a more detailed review of each the following nootropics, simply click on the live link associated with that supplement. And you’ll go to a new page which will provide you with the nootropic’s history, mechanism of action, clinical studies, dosage notes, side effects and recommendations.
You can easily find these acetylcholine supplements on Amazon, GNC, The Vitamin Shoppe, Whole Foods and sometimes even Walmart. And the racetams are available at a few trusted online nootropic vendors.
Table of Contents
Supplements that Boost Acetylcholine
ALCAR boosts acetylcholine. It is a precursor to the synthesis of acetylcholine in the presence of Coenzyme-A. ALCAR donates a “methyl group” to make acetylcholine.
Alpha-Lipoic Acid increases acetylcholine production by activation of choline acetyltransferase and increases glucose uptake. This process supplies more Acetyl-CoA for the production of acetylcholine.
Researchers at Nizam’s Institute of Medical Sciences in Hyderabad, India gave 20 healthy male volunteers 250 mg capsules of standardized Ashwagandha extract for 14 days.
Significant improvements in reaction times were reported at the end of the trial. The study suggests that Ashwagandha extract improves cognitive and psychomotor (physical reaction) performance even when you’re in the best of health.
Bacopa Monnieri (Brahmi) was given to devotees in ancient India to help memorize long passages of text. And enhance cognition.
As an adaptogen, Bacopa helps balance the neurotransmitters acetylcholine, dopamine, and serotonin. And research shows Bacopa inhibits acetylcholinesterase (the enzyme that breaks down acetylcholine). As well as activates choline acetyltransferase. The enzyme that promotes acetylcholine creation.
Researchers searched clinical studies to compare the cognition enhancing effects of Bacopa Monnieri and Ginseng to the popular smart drug Modafinil.
The team found that both Bacopa and Ginseng worked better than Modafinil for improving accuracy, memory and processing speed.
DHA (docosahexaenoic acid) is an omega-3 fatty acid. The highest levels of DHA are found in phosphatidylserine (PS). With lower levels in phosphatidylcholine (PC).
PS and PC are called phospholipids. And make up much of the inner and outer shell of brain cell membranes. Made up largely of DHA, these cellular membranes regulate entry into the cell, and control neuroreceptor function. Which facilitates cellular communication between, and within cells.
Phosphatidylcholine (PC) also contributes the choline needed to synthesize acetylcholine. And DHA regulates calcium oscillations, which are involved in neurotransmitter release, mitochondrial function, gene activation, oxidative stress and brain cell development and growth (BDNF).
A DHA supplement is one of the most important nootropics you can add to your stack. Recommended daily dosage is 1,000 mg of DHA per day.
Ginkgo biloba (Ginkgo or Maidenhair) is known for regulating neurotransmitters, protecting from brain cell degeneration, boosting cerebral circulation and is a potent antioxidant.
Research also shows Gingko’s cognitive enhancing capabilities are due to its effect on the cholinergic system in your brain. It modulates pre-synaptic choline uptake and acetylcholine release, upregulates post-synaptic acetylcholine muscarinic receptors, and has an indirect effect on choline function by modulating the serotonin system.
One study using Cereboost™, a branded form of American ginseng (Panax quinquefolius), which has a high concentration of Rb1 ginsenoside, enhanced the activity of the enzyme choline acetyltransferase (ChAT). ChAT is the enzyme responsible for acetylcholine synthesis.
This ginseng supplement also restored brain microtubule-associated protein 2 (MAP2) as well as acetylcholine concentration. And scientists just discovered that MAP2 is the main “traffic regulator” in neurons in the brain. This neuron traffic signaling system plays a key role in brain diseases like Alzheimer’s.
Gotu Kola (Centella asiatica) is often called “the student herb” in Bali. Because it sharpens the mind. Gotu Kola extract increases dendrite and axon growth in brain cells which helps memory.
Gotu Kola is rich in triterpene saponosides. These triterpenes inhibit acetylcholinesterase (AChE). The enzyme that breaks down acetylcholine. Meaning more acetylcholine is available in your brain.
Huperzine-A is a natural compound extracted from the Chinese club moss huperzia serrata. Huperzine-A is an acetylcholinesterase (AChE) inhibitor. Which means it boosts levels of the neurotransmitter acetylcholine in your brain.
Nootropics users report Huperzine-A provides a boost in mental energy. Without the side effects normally associated with a stimulant. Improved cognition and clear thinking are common when using Hup-A. Many report a boost in short-term memory. Recall is better in the long-term.
Researchers at Walter Reed Army Institute of Research in Washington D.C. found Huperzine-A to be twice as effective in protecting soldiers against the lethal effect of the nerve agent soman, as the leading drug in that role called physostigmine.
Huperzine-A’s effects lasted for six hours compared to only 90 minutes for the drug. Nerve gas used in chemical warfare attack the acetylcholine system in your body and brain.
Iodine is required for the production of thyroid hormones T4 and T3. Thyroid hormone receptors in the brain help regulate the production and use of all important neurotransmitters.
Thyrotrophic-releasing hormone (TRH) increases acetylcholine (ACh) synthesis. One study showed that those with hypothyroidism had significantly decreased acetylcholine in the hippocampus. And that administration of T4 normalized ACh levels. Iodine is required to make T4.
Lemon Balm increases the activity of the neurotransmitter acetylcholine (ACh) in your brain. When your brain sends signals, it uses acetylcholine to keep the signals moving. But once used, your brain removes acetylcholine with an enzyme called acetylcholinesterase (AChE).
The rosmarinic acid in Lemon Balm is an AChE inhibitor. By inhibiting AChE, more acetylcholine is available to boost learning and memory. And Lemon Balm also has cholinergic receptor-binding properties. Which boosts the ability of ACh to bind to its receptors.
Nicotine works primarily by upregulating nicotinic acetylcholine receptors (nAChR) in the brain. Boosting the release of acetylcholine (ACh), dopamine, serotonin, and glutamate. Increasing neural signaling of neurotransmitters and boosting alertness, cognition, memory and mood.
But studies have shown this upregulation of nAChR is dose dependent. And too much nicotine desensitizes these receptors. So low doses of nicotine are key in using nicotine as a nootropic for cognitive benefit.
The National Institute of Drug Abuse conducted a meta-analysis of 41 double-blind, placebo-controlled studies conducted between 1994 and 2008. The analysis found significant positive effects of nicotine on fine motor performance, alertness, attention and accuracy, response time, short-term and working memory.
Phosphatidylcholine serves as a storage pool for the choline needed as a precursor for acetylcholine (ACh) synthesis. ACh is synthesized from choline derived from the degradation of Phosphatidylcholine.
PC performs a 2nd important function in your brain. The hydrolysis of Phosphatidylcholine (by a process called phospholipase A2-catalyzed hydrolysis) is used to make the free fatty acids AA, oleic, linoleic, linolenic and DHA.
These free fatty acids facilitate synaptic transmission by targeting nicotinic ACh receptors using protein kinase C (PKC). This messenger system is needed for long-term potentiation (LTP). Researchers have determined that these fatty acids are critical for learning and memory.
Phosphatidylserine is a phospholipid component of the membrane encasing every one of your brain cells. In fact, Phosphatidylserine is one of the most effective memory boosters known.
PS is an integral part of the flow of crucial neurotransmitters like dopamine and acetylcholine. And phospholipids contain choline which is a precursor to acetylcholine (ACh). So PS will increase ACh levels in your brain. Affecting cognition, memory and mood. And reducing anxiety.
In Russia, Rhodiola Rosea is widely used as a remedy for fatigue, poor concentration, and decreased memory. It’s also believed to make workers more productive.
Rhodiola improves mood by influencing serotonin and norepinephrine levels in your brain. And the ‘feel-good’ opioids like beta-endorphins. It helps repair and grow new brain cells (neurogenesis). Rhodiola activates synthesis and re-synthesis of ATP. And reduces inflammatory C-reactive protein. Protecting your brain cells from oxidative damage.
Researchers at China Pharmaceutical University also found that Rhodiola extract inhibits acetylcholinesterase. Meaning it increases levels of available acetylcholine in your brain.
Supplementing with SAM-e (S-Adenosyl Methionine) to increase muscarinic acetylcholine receptors in your brain can boost neuroplasticity. And increase learning, memory, mood and even smell and vision.
Muscarinic receptors are part of a large family of G-protein-coupled receptors (GPCRs) which are used as an intracellular secondary messenger system.
G proteins work by binding neurotransmitters, hormones, growth factors, cytokine, odorants and photons at the cell surface to the GPCR, and activating that receptor. Everything you see, hear, smell, or taste goes through this signaling process.
SAM-e also has a critical role as a methyl donor (called methylation) in the production and breakdown all the major neurotransmitters in your brain. Including acetylcholine.
Uridine is a precursor to the formation of CDP-Choline which is a precursor to the formation phosphatidylcholine (PC). PC separates into choline and sphingomyelin in your brain. Choline is then available to form acetylcholine (ACh). Optimal ACh levels is crucial for cognitive performance.
Vitamin B1 (Thiamine)
Thiamine contributes to the production of the enzyme PDH (pyruvate dehydrogenase) which is essential for making acetylcholine.
Sulbutiamine is a synthetic derivative of Vitamin B1. It’s simply two Vitamin B1 molecules bonded together. This chemical bond helps thiamine more easily cross the blood-brain barrier. And is often a better alternative in a nootropic stack than just plain Vitamin B1 (thiamine).
Vitamin B5 (Pantothenic Acid)
Vitamin B5 is a precursor in the biosynthesis of Coenzyme-A (CoA). Adding an acetyl group to CoA makes Acetyl-CoA. Choline + Acetyl-CoA go on to produce acetylcholine.
Vitamin B12 (Cobalamin)
Vitamin B12 is a co-factor in the one-carbon cycle that is required for the synthesis of all major neurotransmitters in your brain including acetylcholine, dopamine, GABA, norepinephrine and serotonin.
Typical recommended dosage for nootropic benefit and optimal brain health is 100 mcg or 1 mg of Vitamin B12 (methylcobalamin) per day. Neurohackers older than 40 and those who have a problem with Vitamin B12 absorption should use 100 – 400 mcg or 1-4 mg of B12 per day. See the extended review of B12 for details.
Acetylcholine and the Racetams
Most of the nootropics in the racetam-family of compounds influence acetylcholine (ACh) in one way or another. Your chosen racetam could increase the synthesis of ACh. It could boost acetylcholine receptor density. Or increase the use of acetylcholine through the High Affinity Choline Uptake (HACU) process in parts of your brain. And even modulate the flow of acetylcholine.
This means that use of a racetam in your nootropic stack demands the addition of a quality choline supplement like Alpha GPC or CDP-Choline. To give your brain the ability to make the acetylcholine it requires.
If you neglect to use a choline supplement, you’ll not experience the full benefit of that racetam. And likely end up with a racetam-headache.
Please refer to my Advanced Guide to Choline in Nootropic Stacks for more.
Here are the best racetams for influencing acetylcholine in your brain.
Coluracetam (BCI-540, or MKC-231) is a fat-soluble nootropic in the racetam-class of compounds. And is much more potent than the original racetam, Piracetam.
Coluracetam boosts your brain’s choline conversion to acetylcholine (ACh) through the high affinity choline uptake (HACU) process.
Nefiracetam is a fat-soluble nootropic developed in Japan for the treatment of cerebrovascular disease. This racetam is structurally similar to Aniracetam. And helps modulate GABA levels in the brain which improves memory formation and recall, and provides anti-anxiety and antidepressant benefits.
Nefiracetam also potentiates presynaptic nicotinic acetylcholine receptors in the hippocampus. Which encourages glutamate release and Long-Term Potentiation (LTP).
Noopept is an ampakine nootropic similar in action to the racetam-class of compounds. And considered up to 1000X more potent than Piracetam.
Noopept does not appear in blood samples when taken as a supplement. Instead it elevates concentrations of cycloprolylglycine (CPG) in the brain.
CPG is a dipeptide consisting of proline and glycine which acts as a modulator of acetylcholine transmission, and AMPA receptor function.
Oxiracetam is a water-soluble racetam nootropic. And considerably more potent than Piracetam. Oxiracetam enhances choline-acetyltransferase (ChAT) in your brain. ChAT is the enzyme needed to stimulate acetylcholine (ACh) synthesis.
Oxiracetam also enhances protein kinase C (PKC) which affects M1 acetylcholine receptors. Oxiracetam even demonstrates the ability to repair these receptors when damaged.
And Oxiracetam seems to prevent an imbalance of acetylcholine activity when NMDA receptors are malfunctioning.
Phenylpiracetam is a water-soluble nootropic in the racetam-class of compounds. This racetam increases the density of acetylcholine (ACh), NMDA, GABA and dopamine receptors in the brain.
This translates into more receptors for each of these important neurotransmitters to bind with and boosts their effectiveness.
Phenylpiracetam has a positive effect on physical performance by increasing endurance, and reducing physical and mental fatigue. In fact, these effects are so potent that Phenylpiracetam has been banned from professional sports by the World Anti-Doping Agency.
Piracetam was developed by Romanian chemist, and the godfather of nootropics, Dr. Corneliu E. Giurgea in 1964. This is the first racetam ever developed.
Piracetam potentiates the flow of, and increases the effect of acetylcholine (ACh). And boosts the sensitivity and density of ACh receptors in the brain.
Pramiracetam is a fat-soluble nootropic in the racetam-class of compounds. It has been shown to significantly increase High Affinity Choline Uptake (HACU) in the hippocampus. This action boosts acetylcholine (ACh) use which accounts at least in part for Pramiracetam’s ability to enhance cognition and memory.
Pramiracetam also has a profound effect on the synthesis of the acetylcholine (ACh). Positively affecting encoding of new memories, concentration, cognition and neuroplasticity.
Not using a choline supplement while taking racetams is only one of the ways to you can deplete your brain of acetylcholine. Racetam-headaches happen because your brain will start to literally consume itself to get the building blocks it needs to make acetylcholine.
But what most neurohackers don’t realize is that we have easy access to plenty of anticholinergic medications that will do a great job of depleting your brain of acetylcholine. Drugs that decrease acetylcholine.
Any prescription or over-the-counter medication that blocks the action of acetylcholine is considered an anticholinergic.
These meds include antidepressants, antibiotics, antihypertensives, antipsychotics, and antispasmodics. If it starts with “anti”, it will very likely lower your acetylcholine levels.
Now, I’m not saying don’t use these medications. Just know how critical it is to replace the acetylcholine lost or suppressed while using it, with one or more of the supplements listed in this post.
Acetylcholine Supplements – The Last Word
Optimal levels of acetylcholine are critical for brain optimization and function.
Your diet, medications, some nootropics, and neurological disorders can all contribute to depleted levels of this critical neurotransmitter – acetylcholine.
We have dozens of supplements that can increase the synthesis of acetylcholine (ACh), increase density of ACh receptors, improve how ACh is used, and even amp-up the flow of acetylcholine in your brain.
But the way each of these nootropic supplements work vary from person to person. What works for me may not work as well for you. Experimenting is key to finding the best combination for your unique brain chemistry and genetics.
One final note – if you’re dealing with unusually significant memory loss. Memory loss that feels in your gut like it’s worse than it should be. Don’t take chances on trying every nootropic supplement and hoping for the best. Do yourself and your family a favor. And see a qualified neurologist.
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