Do you notice having trouble remembering names, losing your keys more frequently, or having a lack of motivation? If so, you may need to boost your acetylcholine production, a key neurotransmitter for memory. Plus, new research links acetylcholine to gut health, fatigue, healthy blood pressure, impulse control and other functions throughout the body.

Neurotransmitters

There are 200 recognized neurotransmitters and many different classes or types. These include amino acids (GABA, glycine, etc.), gasotransmitters (nitric oxide, etc.), monoamines (dopamine, serotonin, histamine, norepinephrine, etc.), trace amines (tyramine, etc.), peptides (substance P, etc.), purines (ATP), and others like acetylcholine.

Glutamate (excitatory) is the most prevalent neurotransmitter with function in over 90 percent of brain synapses. GABA, which is an inhibitory neurotransmitter, is the next most prevalent and is present at more than 90 percent of synapses that do not use glutamate. In this eye-opening article, the focus will be on the memory neurotransmitter – acetylcholine.

Acetylcholine

Acetylcholine is our primary memory neurotransmitter, but it does so much more. When the brain is having difficulty with insufficient acetylcholine, several things may occur. Noticeable trouble with remembering names, faces, places, numbers, lists, or instructions may occur. Inability to remember common facts, trouble with understanding verbal or written material, forgetting where you put something, or making simple mistakes may indicate impaired acetylcholine levels or function.

Thinking may be slow. Easily confused, loss of direction or easily lost, social withdrawal or preference to doing things alone may occur. In addition, there may be emotional feelings with lack of joy or passion, loss of creativity and unpredictable feelings with inability to cope.

There may be brain fog, excessive urination, dry mouth, weakness and fatigue especially with physical activity, facial flushing, constipation, gut dysbiosis, gut motility disorders, and gastroparesis. There may be low blood pressure/POTS, or orthostatic hypotension, tachycardia, and large pupil size which may cause light sensitivity.

Acetylcholine Importance

Acetylcholine receptors are found throughout the body and the brain. The brain cells use acetylcholine to help with attention, memory, motivation, alertness, arousal/wakefulness, nerve plasticity, and REM sleep.

In the body, nerves use acetylcholine to communicate to muscle cells in order to contract and function as part of the body’s electrical communication process. It helps with movement of positively charged ions (sodium, potassium, calcium) to cross cell membranes and keep sodium and calcium from building up inside cells. Acetylcholine is also used by the vagus nerve that connects the brain-gut. Choline is needed for metabolism, cholesterol, homocysteine, and methylation.

Acetylcholine and the Gut-Brain Connection

Acetylcholine profoundly influences and plays a crucial role in the gut-brain connection as it works with the vagus nerve or cranial nerve 10. The vagus nerve is the “main nerve highway” that talks to parasympathetic (rest, relax, and digest) and sympathetic (fight, flight, engaged) autonomic nervous system. It is referred to as the cholinergic anti-inflammatory pathway.

Because of its direct function with the parasympathetic and sympathetic nervous system, the vagus nerve helps calm stress, manages inflammation, and dampens immune cell activation within the brain and digestive tract. Acetylcholine is needed for the vagus nerve to do its job to restore homeostasis and reduce intestinal inflammation. When this balance is disrupted, gut health and digestion take a turn for the worse.

Disruption of Acetylcholine in the Gut

Gut motility and flora are greatly impacted by acetylcholine as the neurotransmitter is critical for normal gut function and the digestive tract’s internal or enteric nervous system. Gut flora can activate the vagus nerve via various chemical signals like acetylcholine, which plays a pivotal role in brain and behavior. Depending on the type of gut bacteria (beneficial or non-beneficial) and acetylcholine function, the signals produced by the gut-brain connection may lead to anxiety-producing or anxiety-calming effects.

There are other effects on the gut. Research published March 2018 found that animals that developed disruption in acetylcholine synthesis during prenatal development had significant gut health changes. There was a loss of healthy gut motility or dysmotility, loss of movement within the colon/constipation, intestinal dysbiosis or germ overgrowth, failure to thrive and even death. It led to the conclusion that acetylcholine is necessary for sustained gut motility and survival.

Other research shows us that the choline anti-inflammatory vagus nerve pathway helps the body reduce TNF-alpha affecting the gut-immune system. It does this by regulating the immune system with acetylcholine-producing memory T-cells in the spleen and affects the diversity of gut flora and inflammation.

Scientists found that during excess stress or in a sympathetic/adrenaline state, T-cells were unable to secrete acetylcholine which led to an impaired immune defense system in the gut. Germ overgrowth occurred along with increased TNF-a and gut inflammation.

Neurodegenerative disorders like Parkinson’s disease are impacted by the cholinergic-anti-inflammatory pathway and vagus nerve. In Parkinson’s disease, years before movement problems with gait and balance difficulties and tremors occurs, there is a change in gut health and brain, i.e. constipation and depression.

Research published February 2018 shows a decrease of acetylcholine in the gut, changes in brain dopamine levels and increased pro-inflammatory activity in the animal model of Parkinson’s disease. Study results suggested that acetylcholine dysfunction and inflammation of the gut-brain path may explain the early symptoms of Parkinson’s and increase the vulnerability of dopamine-rich areas to oxidative stress in the brain.

Acetylcholine is also involved with managing impulse control, obsession control, and metabolic function. Research published in the journal Frontiers of Neuropsychiatry February 2017 found that some patients with obesity and type 2 diabetes have been found to have an over-expression of acetylcholine-degrading enzymes. This causes acetylcholine to be broken down too easily. Scientists are also studying this effect in those who have compulsive, food obsession and eating disorders.

How is Acetylcholine Produced?

The body makes acetylcholine through a series of steps and requires several nutrients like choline and B vitamins, i.e. B2, B6, B12, and folate. Acetyl coenzyme A (CoA) together with choline make acetylcholine. The nutrient, pantethine, which is the coenzyme form of pantothenic acid/vitamin B5, fuels the production of CoA. In fact, pantothenic acid deficiency decreases the availability of acetylcholine within the parasympathetic nervous system. Fascinating research shows us that the beneficial bacteria species Lactobacillus produces acetylcholine.

Acetylcholine Needs and Sources

The Standard American Diet lacks adequate choline to reach most adult and children’s needs according to the Linus Pauling Institute. Adequate acetylcholine RDI intake for men is 550 mg and women 425 mg per day. Children need 200 - 350 mg per day.

Foods highest in acetylcholine include beef liver (3 ounces provides 356 mg), wheat germ (1 c = 202 mg), whole egg (large = 147 mg), beef (3 oz = 97 mg), salmon (3 oz = 75 mg), chicken (3 oz = 73 mg), broccoli (1 c = 63 mg), milk (1 c = 38 mg) peanuts (1 oz = 15 mg). Other vegetarian and botanical sources for acetylcholine include bitter orange, common bean, foxglove, mistletoe, mung bean, nettle species, pea, radish, spinach, squash, and wild strawberry.

Think about your diet and what your children or parents eat. Vegetarians, dairy-free, and those who consume the Standard American Diet are likely to not get enough acetylcholine in their diets.

Drugs and Toxins Affect Choline

Several medications are anti-cholinergic and lead to consequences like increased risk for dementia. In addition, drugs that affect folate metabolism like methotrexate may consequently affect metabolism of choline leading to increased choline needs. You may read more about this in the article Dementia Risk Linked with Common Medications. 

Several pesticides and insecticides which contain organophosphates directly impact choline and impair receptor site function and can even trigger a cholinergic crisis in the body. Common insecticides include malathion, parathion, diazinon, fenthion, and trichlorfon and other insecticide types such as carbamate, organochlorine, and pyrethroid insecticides. Heavy metal toxicity from lead, mercury, etc. can also impair and disrupt choline function in the body. EMF exposure such as that from electrical, cell phones, wireless technology, and MRI exposure can cause microleakage of mercury out of dental fillings which can affect acetylcholine. 

Critical functions in the body and brain rely on acetylcholine. The brain-gut vagus nerve connection requires choline to maintain a balance in function, manage homeostasis, and repair. At the same time, numerous chemicals, toxins, medications, and dietary insufficiency can lead to insufficient levels of acetylcholine.

Eggs, a rich source of choline, have gotten a bad reputation over the last few decades, but are now gaining an acceptance as a healthy food. Is the epidemic of gut disorders and cognitive challenges a reflection of impaired acetylcholine? There aren’t any easy ways to lab test acetylcholine levels in the body. Rather, if you are losing your keys, forgetting names and faces, lost interest, and have some underlying gut distress, work on optimizing your support for acetylcholine.