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Neurotransmitters are the messenger chemicals in our brains that dictate how we feel. You can think of them as hormones for the brain. Neurotransmitters were first described in 1921 when German-born pharmacologist Otto Loewi noticed the vagus nerve secreted something when stimulated. That “something” was acetylcholine. It slowed the heartbeat when released. 

Neurotransmitters help make us happy, focused, driven, sleepy, confident, calm, creative, and more. Some are stimulating (“excitatory”), and some are calming (“inhibitory”). Too much of any of these chemical messengers can be just as problematic as too little. The key is maintaining an overall balance while they ebb and flow to adapt to our daily activities and situations. In this article, we’ll talk about acetylcholine.  

What is Acetylcholine? 

As mentioned, acetylcholine (“ACh”) was the first neurotransmitter discovered. Initially, it was researched for its role in the sleep-wake cycle. Now, it’s studied for many other functions in the brain and throughout the body. However, it’s best known for its effects on the brain.  

You can think of acetylcholine as the “mental sharpness” neurotransmitter. Scientists have found that the absence of acetylcholine in the hippocampus (the memory center of the brain) causes forgetfulness. Acetylcholine synthesis begins in nerve terminals with acetyl coenzyme A (“acetyl-CoA,” synthesized from glucose) combined with a molecule called choline.  

Choline is a nutrient that’s a lot like the B complex vitamins. It’s sometimes called vitamin B4; however, it doesn’t technically qualify as a vitamin because we can make small amounts of it in the liver in the form of phosphatidylcholine. Choline is essential for overall human health, growth, and repair.  

Getting enough choline is vital for healthy cell membranes, gene expression, and fat breakdown. It’s super important for brain and nervous system health—After all, acetylcholine depends on it. 

Acetylcholine is the main neurotransmitter of the parasympathetic nervous system, the “rest-and-digest” part of the autonomic nervous system. It’s located at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subtype of sympathetic effector junctions, the motor end plate of vertebrate muscles, and many other sites within the central nervous system (CNS) and peripheral nervous system (PNS).  

It’s stored in small vesicles at the ends of ACh-producing neurons. 

Acetylcholine Terminology 

Whenever you hear or see the word “cholinergic,” it refers to something associated with acetylcholine.  

The “cholinergic system refers to the way acetylcholine works in the body. Cholinergic neurons are cells that produce acetylcholine. The parts of the body that affect or are affected by acetylcholine are dubbed “cholinergic.” ACh receptors are called cholinergic receptors (or ACh receptors). 

There are two types of receptors in the body that respond to acetylcholine: 

  • Nicotinic receptors – Not surprisingly, these are activated by nicotine. They are located in the brain and skeletal muscles. 
  • Muscarinic receptors – These receptors are in the other parts of the body, including the heart, digestive tract, glands, and some places in the brain. 

These two categories of receptors allow acetylcholine to dictate the functioning of those tissues it interacts with. 

Acetylcholine’s Functions 

Acetylcholine has multiple roles within the central nervous system. However, exactly how it works is not well understood. We know it plays a key role in the following: 

  • Learning, memory, and creativity 
  • Movement: muscle contraction 
  • Breathing (acetylcholine and histamine work together) 
  • Promoting peristalsis, the movement of food through the digestive tract. 
  • Blood vessel health  
  • Increasing bodily secretions 
  • Slowing heart rate 
  • Controlling the sleep-wake cycle and impacting sleep quality 

When acetylcholine is at optimal levels, a person feels “on their game” –energetic, youthful, quick-thinking, creative, optimistic, outgoing, adventurous, and open to new experiences. When it becomes imbalanced –either too high or too low—it may lead to exhaustion, depression, paranoia, anxiety, or isolation.  

Low Acetylcholine  

Low acetylcholine levels are particularly associated with symptoms of mental decline. 

Signs, Symptoms, and Conditions 

An acetylcholine decline may appear subtly with brain fog, occasional forgetfulness, and lack of focus. From there, if not addressed, it may progress to neurodegenerative disease. Some signs and symptoms of low acetylcholine levels include:  

These symptoms may also be caused by other things but are a good reason to get your neurotransmitters checked. Without enough acetylcholine, you won’t feel like you’re performing at your highest level. 

What Depletes Acetylcholine? 

Low acetylcholine levels can come from production, uptake, or conversion issues which go back to the usual suspects: trauma, toxins, and thoughts. All three create stress and inflammation in the body, leading to many imbalances, including acetylcholine depletion. Here are a few examples: 

  • Chronic mental stress – Chronic stress depletes acetylcholine levels.  
  • Nutrient deficiencies – Deficiencies in nutrients, especially choline and B-vitamins, can lead to low levels of ACh. 
  • Gut Dysbiosis – This can create nutrient deficiencies by impacting absorption.
  • Traumatic Brain Injury (TBI) – A TBI may lower nicotinic acetylcholine receptors, reducing acetylcholine activity.  
  • Choline deficiency – You cannot make acetylcholine without adequate levels of choline. The liver doesn’t make enough, so we must get it in our diets. A choline deficiency may even lead to a fatty liver or liver damage.
  • Metal toxicity Aluminum and mercury are two toxic metals that may lead to low acetylcholine levels. Certain mercury compounds have a high affinity for acetylcholine receptors. Eventually, this can lead to low acetylcholine levels.  

Often, a combination of these factors disrupts acetylcholine signaling. Over time, these contribute to chronically low acetylcholine levels and all the health effects that go along with that. 

What Can Help Raise Acetylcholine? 

Of course, there are medications out there to raise acetylcholine levels. They work by inhibiting the enzymes that would otherwise break down acetylcholine, so it stays higher longer. That main enzyme is called acetylcholinesterase. The –ase at the end indicates that it serves as an enzyme.  

One strategy for raising acetylcholine levels is increasing choline, which can increase ACh neurotransmission. Other strategies involve keeping acetylcholine active longer in the brain by slowing the breakdown enzyme, cholinesterase, by inhibition. These strategies may include the following dietary and lifestyle changes: 

  • Eating plenty of choline-rich foods – Include beef (especially beef liver and other organ meats), fish roe (caviar), egg yolks, fish, shiitake mushrooms, cruciferous vegetables, and sunflower seeds. 
  • Choline-promoting dietary supplements: These are nootropics like alpha-GPC citicoline (CDP-choline), phosphatidylcholine, and phosphatidylserine. 
  • Organ glandular supplements – These have the constituents naturally found in organ meats in concentrated pill form. You can find excellent quality glandular supplements in our online store.
  • Eating Acetylcholine-containing foods – Eggplant, peas, radishes, spinach, squash, and wild strawberry have all been found to contain acetylcholine.  
  • Herbal supplements  These herbs or herb derivatives may inhibit acetylcholine breakdown, keeping it active in the brain longer: Bacopa, Ginkgo biloba, rosemary, Nettle, and Gotu Kola.  
  • Spices – According to the National Institutes of Health’s Library of Medicine, acetylcholine also naturally occurs in cardamom and black pepper.  
  • Addressing gut health A probiotic strain, Saccharomyces boulardii, was shown to improve cognitive decline associated with gut dysbiosis. 

A lower carbohydrate diet with plenty of healthy fats, including organ meats, can be helpful in optimizing acetylcholine levels.  

High Acetylcholine 

It’s also possible (though rare) to have excessively high levels of acetylcholine.  

Signs, Symptoms, and Conditions 

When acetylcholine rises too high in the synapses between the nerves, or when there’s damage to the receptors, it can lead to “nicotinic” or “muscarinic toxicity.” Some signs and symptoms of higher-than-normal acetylcholine levels include:   

  • Increased salivation 
  • Muscle cramps or twitches 
  • Diarrhea 
  • Blurry vision 
  • Panic, manic, or anxiety disorders 
  • Parkinson’s disease – low dopamine levels allow acetylcholine to rise too high 
  • Neuromuscular paralysis 

What Causes Elevated Acetylcholine? 

One of the leading causes of acetylcholine excess is high levels of free glutamates. These often come from stress, allergies, and inflammation. Another cause is toxic exposure that inactivates the enzyme that breaks acetylcholine down. As a result, it rises to toxic levels. This is called a cholinergic crisis. Causes include: 

  • Exposure to organophosphates – Organophosphates are in pesticides, insecticides, and herbicides. The highest concentrations are residues on apples, grapes, spinach, cucumbers, and potatoes. It’s more likely to get to toxic levels while working with these chemicals than consuming residues on produce.
  • Exposure to nerve gases – Nerve gasses are used in chemical warfare. Those who have served in combat may have high acetylcholine from nerve gas exposure.
  • Black widow spider venom – Leads to excessively high ACh levels, leading to spasms, paralysis, and even death. If you get a black widow spider bite, it’s time to head to the ER. 

Stress and toxins can cause acetylcholine levels to go over the top. That’s where pharmaceutical medications have their place.

What Can Help Lower Acetylcholine? 

In the hospital setting, “firemen” doctors use anticholinergic (acetylcholine-blocking) medications like scopolamine, also called “Devil’s Breath,” to temporarily interrupt acetylcholine transmission. Medical doctors have a variety of medications at their disposal for lowering dangerously high acetylcholine. The interventions do this by either decreasing the release of acetylcholine or promoting acetylcholinesterase. Examples include the following: 

  • Botox – This medication comes from botulinum toxin. It interferes with acetylcholine in the muscles where injected, preventing muscle contraction. This can help minimize the appearance of wrinkles, as the skin is prevented from contracting.
  • AChE (acetylcholinesterase) inhibitor medications – These are pharmaceutical drugs that impact the enzymes used in acetylcholine production. One example is Razadyne (galantamine), a medication used for mild to moderate dementia.  
  • Anticholinergic medications – These medications interfere with acetylcholine and may be used to balance choline and dopamine in Parkinson’s disease. But they are also used to treat a variety of other conditions, including gastrointestinal and respiratory disorders. They have been shown to make learning new information difficult in both human and animal studies.  

It’s very rare to have toxic levels of acetylcholine — It usually occurs with exposure to high levels of synthetic chemicals. In those cases, medical intervention may be necessary.

Don’t Guess, Test! 

Many people turn to questionnaires or quizzes to find out their neurotransmitter levels. While doing so may give you some idea, it’s not accurate, and depending on which one you use, you could be completely off-base. At The Wellness Way, we can test your neurotransmitter levels to determine what the imbalance is, and how the body is being overstimulated or understimulated. Then we can find out where the problem is, and which signals are reaching the brain. We often begin with food allergy testing or stool testing, as imbalances in the gut greatly influence neurotransmitter activity. After assessing your overall situation, we may also opt to test your neurotransmitters directly –if deemed necessary. Once we have the results, we’ll create a customized plan of action for helping your body and brain get back to balance. Contact a Wellness Way Clinic today to start feeling like yourself again. 

Resources/Citations: 

  1. Acetylcholine | Definition, Function, & Facts | Britannica 
  2. Acetylcholine – Neuroscience – NCBI Bookshelf (nih.gov) 
  3. Neuropharmacology of Sleep and Wakefulness – PMC (nih.gov) 
  4. Traumatic brain injury: central and peripheral role of α7 nicotinic acetylcholine receptors – PubMed (nih.gov) 
  5. Oral exposure to aluminum leads to reduced nicotinic acetylcholine receptor gene expression, severe neurodegeneration and impaired hippocampus dependent learning in mice – PubMed (nih.gov) 
  6. Choline | The Nutrition Source | Harvard T.H. Chan School of Public Health 
  7. Highly Simple Deep Eutectic Solvent Extraction of Manganese in Vegetable Samples Prior to Its ICP-OES Analysis – PubMed (nih.gov) 
  8. Microsoft Word – braverman.test.doc (tripod.com) 
  9. Saccharomyces boulardii ameliorates gut dysbiosis associated cognitive decline – PubMed (nih.gov) 
  10. Cholinergic Crisis – StatPearls – NCBI Bookshelf (nih.gov) 
  11. Presentation and Treatment of cholinergic Crisis in the setting of Carbamate poisoning – Nguyen – 2021 – Clinical Case Reports – Wiley Online Library. 
  12. Acetylcholine | C7H16NO2+ – PubChem (nih.gov) 
  13. Dietary Neurotransmitters: A Narrative Review on Current Knowledge – PMC (nih.gov) 
  14. Acetylcholine: What it is, function, and links with health (medicalnewstoday.com) 
  15. Nerve Agent – an overview | ScienceDirect Topics 
  16. The interaction of acetylcholine and histamine on human bronchial smooth muscle contraction – PubMed (nih.gov) 
  17. Interactions of acetylcholine receptors with organic mercury compounds – PubMed (nih.gov) 
  18. Physiology, Acetylcholine – StatPearls – NCBI Bookshelf (nih.gov) 
  19. Acetylcholine – Neuroscience – NCBI Bookshelf (nih.gov) 
  20. Choline’s role in maintaining liver function: new evidence for epigenetic mechanisms – PMC (nih.gov)
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