Acetylcholine: How and Why to Optimize the Synthesis of this Vital Neurotransmitter

10/28/2018

We couldn't live without acetylcholine (ACh). It's an important neurotransmitter within the body and, in fact, was the very first neurotransmitter discovered. The moving title of this article was chosen to impress upon the reader the importance of this neurotransmitter to processes within the body that require movement, from skeletal muscle or smooth muscle. It's also vitally important for brain function, playing a key role in memory, learning and cognition. It functions to relay signals from one neuron to another in the central nervous system and from a neuron to a muscle fiber in the peripheral nervous system. The production of ACh, symptoms and causes of deficiency and how best to treat low ACh will be discussed, but first we'll start with a basic physiology lesson to help you appreciate the function of ACh within the nervous system.

The nervous system is divided into two branches called the autonomic and somatic nervous systems. The autonomic nervous system is our "automatic" nervous system that we cannot voluntarily control. If you get sweaty when nervous or your heart rate increases when you're excited that's your autonomic nervous system controlling your body's response. Your somatic nervous system is your "voluntary" nervous system. This part of the nervous system controls skeletal muscles, like those in my fingers as I type this. You can see from image 1 that ACh is used in both of these branches of the nervous system.

Image 1. Somatic and autonomic nervous system

The autonomic nervous system is further divided into the sympathetic and parasympathetic branches of the nervous system. The parasympathetic nervous system is engaged most of the time in a healthy person. The sympathetic nervous system becomes engaged during times of stress or excitement. The sympathetic branch uses ACh to relay messages but also uses epinephrine and norepinephrine. The parasympathetic nervous system relies solely on ACh to function properly. The parasympathetic nervous system is important for proper digestion, gut motility, salivary flow, lacrimation (tears) and bladder function. The nerve fibers of the parasympathetic nervous system originate from the brain stem and sacral region. The parasympathetic nerve fibers originating from the brain stem are cranial nerves III, VII and IX. Cranial nerve X, the vagus nerve, also contains parasympathetic nerve fibers. A well-functioning vagus nerve is extremely important for all aspects of digestion including stomach acid secretion, pancreatic secretion, bile flow and peristalsis, which is the wave of muscle that moves food through the intestines. (Stakenborg, 2013) The vagus nerve is also very important for regulating heart rate. ACh creates an inhibitory response to cardiac muscle resulting in a slowed heart rate. This is different than other receptors within the parasympathetic system that result in a general increase in activity.

Image 2. Sympathetic and parasympathetic nervous system

By reviewing the different functions of the sympathetic and parasympathetic nervous system in image 2 one can already start to get an idea of what a deficiency in ACh might look like. The symptoms of deficiency are as follows:

Symptoms of Acetylcholine Deficiency

Constipation/gastroparesis
Memory problems
Difficulty with word recall when speaking
Learning difficulties
Dry mouth
Dry eyes
Orthostatic hypotension
Low muscle tone
Depressed mood
Fast heart rate
Chronic inflammation
Emotional instability

Because ACh is so important for nervous system conduction within the brain, a deficiency in ACh has been linked to Alzheimer's disease (AD) and dementia. (Francis, 2005) The enzyme that breaks down acetylcholine is called acetylcholinesterase. Several drugs have been developed for the treatment of Alzheimer's disease that inhibit this enzyme thus increasing ACh levels. These drugs are donepazil, rivastigmie, galantamine. These drugs have not been shown to reverse the effects of AD, they merely stabilize or slow the rate of cognitive decline. As well, some patients don't respond at all to them. (O'Brien, 2010) They also have many side effects due to their systemic effects of increasing ACh levels throughout the body when the goal is to increase ACh in the brain alone. Some of the side effects include nausea, vomiting, diarrhea, muscle cramps, weight loss, headache, insomnia, hallucinations, fatigue, hypertension and frequent urination. (medicine.net)

It's possible that the decline in acetylcholine levels in AD and dementia are due to a deficiency in the precursors needed to make it. So, let's talk about how acetylcholine is made next.

Acetylcholine synthesis

The synthesis of acetylcholine is actually fairly simple as a whole, yet complex in the details. To make acetylcholine we need choline and an acetyl group. The preferred source for the acetyl group is acetyl CoA which is derived from pyruvate, the end product of glycolysis. Research showing this dates as far back as 1936 when scientists incubated animal brain cells in various medium and found that glucose, pryuvate and lactate all equally resulted in an increase in ACh production. Oxygen was needed as well. They stated, "We know now, of course, that acetylCoA (AcCoA) is required for ACh biosynthesis and that it must be the substance produced during the combustion of glucose, lactate or pyruvate in the brain that gives rise to ACh." (Quastel, 1936) Their work was corroborated by researchers in 1979 who stated, "Acetylcholine is synthesized from acetyl CoA and choline in the cytoplasm. Glucose and pyruvate are the preferred precursors of the acetyl carbons of acetylcholine in adult mammalian brain." (Gibson, 1979)

The enzyme that cleaves the acetyl group from acetyl CoA and attaches it to choline is choline acetyltransferase (ChAT) as seen in image 3.

Image 3. Acetylcholine synthesis

So, how do we then get acetyl CoA from glucose and pyruvate? This is where it gets a little more complicated. Those who have studied and understand the Citric Acid Cycle will recognize this information. For those who haven't studied this: the Citric Acid Cycle is a key process involving many steps by which mitochondria make energy. This process is heavily dependent on B vitamins. Image 4 shows the many steps and enzymes involved in this process along with the B vitamins that act as cofactors for those enzymes. The one enzyme I will focus on here is PD that is seen below pyruvate at the top of image 4. PD stands for pyruvate dehydrogenase. It's role is to convert pyruvate into acetyl-CoA.

Image 4. Citric Acid Cycle.

(Image Source: B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review)

I've discussed pyruvate dehydrogenase before in my lecture "Thiamine Deficiency in Children with Special Needs". I've posted the whole lecture below for those who want to know all of the details.

Essentially PD is dependent on adequate levels of thiamine (B1), riboflavin (B2), alpha lipoic acid and niacinamide (B3). In addition, the precursor to coenzyme A (CoA) is pantothenic acid (B5). All of these B vitamins must be present in adequate amounts in order for acetyl CoA to be made. (Stacpoole, 2012) Particularly noteworthy is the role that thiamine plays in ACh production. "The role of thiamine as a crucial coenzyme in neuronal metabolism of carbohydrates and neurotransmitters, especially acetylcholine, has been well elucidated." (Hirsch, 2011) The administration of benfotiamine, a form of thiamine, alone has been shown to reverse the symptoms of Alzheimer's disease, which has been linked to low ACh levels. (Pan, 2016)

Deficiencies in these B vitamin cofactors is most often due to gastrointestinal malabsorption. Yeast overgrowth is a common cause of malabsorpton, especially of B vitamins. The best testing to determine a need for these B vitamins is organic acid testing. Results like the ones seen in image 5, for example, indicate a significant deficiency in B1, B2, B3 and B5. These are results for a child who has Down syndrome and is likely also deficient in ACh due to her B vitamin deficiencies, not her extra chromosome. The deficiencies in this child were due to small intestinal bacterial and fungal/candida overgrowth. Addressing these deficiencies along with the root cause of malabsorption is key to optimizing ACh synthesis.

Image 5. Organic acid vitamin deficiency markers

That leaves us to discuss choline as the other important half of acetylcholine. Choline is an essential nutrient that must be obtained from the diet. Because it is water-soluble the body does not store it, so daily consumption of this nutrient is important for consistent production of acetylcholine to occur. Some choline synthesis within the body is possible, however the production of choline is heavily dependent on a properly functioning methylation cycle. Many genetic and environmental variables exist around methylation.

Foods highest in choline include eggs (yolks) and meat, so vegans and vegetarians are at risk for being low in choline. Supplementation is possible by taking lecithin sourced from soy or sunflower. Lecithin is rich in phosphatidylcholine (PC), which is a precursor to choline. Citicoline and CDP-choline are other forms of choline that have been shown to enhance memory and cogntion. (Gareri, 2015; Fioravanti, 2006) Choline bitartrate should be avoided. It's the most commonly used form because it's the cheapest. It also is the least reliable form for impacting brain levels of choline (Lippelt, 2016) I prefer PC over other sources of choline because the production of PC is the second largest draw on methylation than all other process that require methylation combined. (Bertolo, 2013) Image 5 shows the production of PC from phosphatidylethanolamine via PEMT (phosphatidylethanolamine N-methyltransferase), a process that occurs in the liver. Because cell membranes consist largely of PC the body is required to make it often to keep up with cellular repair and growth. By supplying PC as a supplement this eases up on methylation and allows more methyl groups to be used for other methylation dependent processes.

As well, supplementing with PC has been shown to increase acetylcholine synthesis. Dr. Steven Heizel from the Department of Nutrition, School of Public Health and School of Medicine at the University of North Carolina stated, "Acetylcholine synthesis can be influenced by the availability of choline...its manipulation by changing the diet is likely to be a powerful tool for improving human performance.". (Heizel, 2006)

Image 5. Methylation and choline synthesis

The stage of life that has been shown to be most dependent on dietary choline is fetal development. Dr. Heizel has written, "Choline is critical during fetal development, when it influences stem cell proliferation and apoptosis, thereby altering brain structure and function." (Heizel, 2006) Researchers recently tested two groups of mothers who were in their third trimester of pregnancy. They supplemented one group with 480 mg of choline per day and the second group received 980 mg of choline per day. They then followed up by testing the infants at 4, 7, 10 and 13 months old for processing speed and visuospatial memory. Their results showed "maternal consumption of approximately twice the recommended amount of choline during the last trimester improves infant information processing speed." (Canfield, 2018)

Genetic variations in mothers can alter choline requirements as well. Specifically variations in PEMT and MTHFR1 genes can alter endogenous synthesis of choline. Maternal dietary choline intake can influence global gene methylation and ultimately gene expression in the unborn child. (Bennett, 2016). Because not all mothers know their PEMT or MTHFR1 gene status supplementing with choline during pregnancy at approximately 980 mg per day, as was done in the study above, may help to ensure adequate levels are available for proper infant brain development. In addition, vegans are at high risk for being choline deficient and should definitely consider supplementing. Vegetarians who eat eggs daily are less likely to be deficient. One egg contains about 150 mg of choline.

Natural cholinesterase inhibitors

Because many people are looking to avoid the side effects from pharmaceutical cholinesterase inhibitors, natural cholinesterase inhibitors have grown in popularity in recent years. Using such compounds to address ACh deficiency does not address the root cause. The root cause of ACh deficiency is most often rooted in a deficiency in one or several of the precursors needed to make it. The preferred means to address ACh deficiency is to provide the body with necessary precursors in amounts that have been determined to be individual for each person based on diet, labs, history and symptoms. Using cholinesterase inhibitors can include side effects as it's interfering with the body's ability to naturally eliminate excess ACh when needed. I'll list a few of these compounds below, but want to highlight that root cause should be addressed first. In addition, when working with children it's important to use natural cholinesterase inhibitors with the fewest side effects and highest record for safety.

Image 6. Bacopa monnieri and Gotu Kola supplement

Bacopa monnieri (also known as brahmi, water hyssop, and Herpestis monniera) is one of my favorite nootropic herbs. It has the lowest chance of creating side effects over other forms of cholinesterase inhibitors. "Emerging research demonstrates several mechanisms of action—acetylcholinesterase inhibition, choline acetyltransferase activation, b-amyloid reduction, increased cerebral blood flow, and monoamine potentiation." (Aguiar and Borowski, 2013)

One side effect that is possible with Bacopa is loose stools. This is likely due to increased levels of ACh. The dose can be reduced if this occurs. However, Kumar, et al stated "Bacopa in syrup form, equivalent to 1 gm dried Bacopa daily, for three months in 40 school children aged 6–8 years, showed improvement in immediate memory, perception, and reaction performance without any side effects." (Kumar, 2016).

Gotu Kola (also known as Centella asiatica) is another favorite nootropic herb of mine due to the research supporting it's efficacy and few reported side effects. "Several mechanisms of action of C. asiatica were demonstrated for enhancing cognitive function, such as the inhibition of acetylcholinesterase activity, reduction of phospholipase A2 (PLA2) activity, protection against ß-amyloid formation, and protection from brain damage." (Puttarak, 2017)

Gohil et al report "CA has no known toxicity in recommended doses. Side effects are rare but may include skin allergy and burning sensations (with external use), headache, stomach upset, nausea, dizziness, and extreme drowsiness which tend to occur with high doses of the herb." (Gohil, 2010)

Both Bacopa and Gotu Kola were used in a formula that was tested in children with ADHD. It was not only shown to be effective but "No serious adverse events were reported, and the rate of even mild adverse events among CHP-treated patients was actually less than that of placebo. (Katz, 2010). (CHP is compound herbal preparation.)

Huperzine A is extracted from Huperzia Serrata, a firmoss, which has been used for various diseases in traditional Chinese medicine for fever and inflammation. It has potent cholinesterase inhibition activity. (Wang, 2006) While it has been shown to be effective for improving memory due to mechanisms other than just cholinesterase inhibition (Zhang, 2008), it has not traditionally been used in children and no studies exist reporting it's efficacy or safety in children. Use in children has been deemed "possibly safe" when taken for less than one month. (WebMD)

Potential side effects include nausea, diarrhea, vomiting, sweating, blurred vision, slurred speech, restlessness, loss of appetite, contraction and twitching of muscle fibers, cramping, increased saliva and urine, inability to control urination, high blood pressure, and slowed heart rate. (WebMD)

For these reasons, along with focusing on addressing root cause, I don't typically recommend using Huperzine A in my patients.

Down Syndrome

Because choline has been shown to optimize brain development and methylation is necessary for optimal choline synthesis, choline supplementation in the Down syndrome model has been tested. Dr. Barbara Strupp and her team at Cornell University have done some very important and clinically relevant work in this area. They first wrote about the potential benefit of choline supplementation prenatally in pregnant mothers carrying an infant with Down syndrome in 2016. In this review article they explain the cognitive deficits related to cholinergic pathways in mice that are engineered to have an extra chromosome (Ts65Dn mice) that correlates with that in human trisomy 21. They stated, "Using the Ts65Dn mouse model of DS/AD, our group has identified a putative novel therapeutic intervention that holds great promise for improving cognitive outcome and offering neuroprotection to the cholinergic projection system in DS; namely, supplementing the maternal diet with additional choline during pregnancy and lactation." (Strupp, 2016)

They moved on in 2017 with researching actual maternal choline supplementation (MCS) in the Ts65Dn mouse model. They were able to state, "These results support the lifelong attentional benefits of MCS for Ts65Dn and 2N offspring and have profound implications for translation to human DS and pathology attenuation in AD." (Strupp, 2017)

In 1986 a report of supplementing phosphatidylcholine in a 2.5 year old child with Down syndrome was published. They reported no other supplements given. After 7 months "The child showed a definitive increase in speech and language skills as well as general motor skills which exceeded same aged Down Syndrome peers experiencing like training programs." (Cantor, 1986)

Image 7. Supplement of benfotiamine, a safe and effective form of thiamine

Thiamine supplementation at 50 mg given three times per day has also been shown to improve speech, mood, energy and cognition in adults with Down syndrome. (Reading, 1979) The mechanism behind these changes are likely due to an increase in ACh as well as the many other benefits thiamine supplementation provides.

If you've given your child with Down syndrome a natural cholinesterase inhibitor and seen improvements in gross motor skills, cognition, speech and overall energy levels it's potentially related to an underlying deficiency that has not been properly addressed. This can happen even when giving a multivitamin that contains the cofactors necessary for ACh synthesis if the levels are not high enough for your child's specific needs or malabsorption has not been addressed. If an underlying deficiency goes undetected and untreated other biochemical needs of the body can go unaddressed. Thiamine deficiency, for example, is something I've detected in many of my patients with Down syndrome. It's function in ACh synthesis is just one of many ways thiamine supports brain function and overall health. Thiamine is essential for glucose metabolism, which must be optimized for proper brain function. Optimal glucose metabolism is needed in the brain for more than just ACh synthesis (Mergenthaler, 2013)

Steps to optimize ACh synthesis for your child

Review signs and symptoms of ACh deficiency with their physician. Determine if need to support ACh synthesis exists.
Test for B vitamin deficiencies using organic acid testing. Clues to B vitamin deficiencies can be seen in routine labs as elevated fasting blood sugar, low ferritin, elevated MCV, among others.
Supplement with phosphatidylcholine, especially when eggs and meat are low in the diet
Supplement with phosphatidylcholine if pregnant or breastfeeding, especially if following a vegan or vegetarian diet
Supplement with appropriate levels of B vitamins specific for your child as indicated by test results
Address underlying root cause for malabsorption of B vitamins. Organic acid testing and stool analysis can detect gastrointestinal issues contributing to malabsorption.

Remember, every child with Down syndrome is unique. Some may have a significant need for addressing ACh deficiency and some may not. "With full trisomy, intuitively it might be assumed that expression levels of triplicated genes are 1.5-fold that of the euploid population. However, this is not so." (Strydom, 2016)

27 Comments

Susan Nash

10/31/2018 05:59:13 am

If you have methylation issues, Betaine can help spare your choline. I noticed that if I stopped Betaine I get a kind of anhedonia depression. I was able to trace that back to my impaired methylation chewing up choline.
There are also PEMT mutations that can impact Post menopausal women that are very common in women descended from colonial North Carolina. Women with these mutations get organ disfunction like fatty liver disease if fed a choline deprived diet.
CDP Choline also helped me with a problem where my body would overheat from lack of sweat.

Erica E Peirson

2/6/2019 09:37:57 am

There is one report from 2002 of lithium given with a cholinesterase inhibitor called tacrine. Both of these were given in extremely high doses to lab animals and did cause brain damage. The dose of lithium given was approximately 500 mg/kg per day and was in the form of lithium chloride. This is very different from the OTC form and dose of lithium that most parents are using which is lithium orotate at 5 mg per day. Giving low dose lithium orotate with a non-toxic whole herb cholinesterase inhibitor like Bacopa poses little concern, but you should discuss the use of these two supplements together with your doctor.

Sara Lance link

2/28/2021 10:10:07 am

Dr. Peirson - I just want to thank you so much for posting the information on your website. It has been life changing for me! As a long-term vegan (over 20 years), I started developing a very strange set of symptoms - felt like I was losing my mind! Your list of symptoms for choline deficiency matched perfectly! Almost immediately after I started eating eggs, I was able to poop normally again, and over the following months all my other symptoms improved as well. My heart, GI tract, brain, eyes, liver and whole body thank you whole heartedly!

Erica

2/28/2021 10:54:07 pm

I'm so happy you found some resolution to your health issues!!

Peter

7/1/2021 01:54:27 am

I have never came across such an informative article in regard to my health such as this one..
i believe its a gem which will help even to solve behavioral disorders in us and children.
its purely feels like salvation

Erin

7/16/2021 10:50:42 am

I wish this would become more commonplace knowledge in the medical community. I've been suffering from dysautonomia/POTS for over 7 years. They keep trying to prove Sjogren's, but I come up negative. I am on a cholinergic agonist for extreme dry mouth, dry eyes, dry vagina, anhidrosis, etc. I also have vertigo, orthostatic hypotension, problems emptying my bladder, gastroparesis, insomnia, migraines, chronic, crippling fatigue, muscle weakness, exercise intolerance, and total anhidrosis. I had autonomic testing done and it said I don't have dysautonomia, even with all these symptoms. It also said I could sweat normally, but I have total anhidrosis. It's so bad that my blood pressure went up to 186/169 (after a 20 minute, ice-cold shower) just from being exposed to 80+ degree heat for 10 minutes. They add acetylcholine to the site and I felt that it invalidated the results if I'm lacking it and that is why I can't sweat.

This article has been so exciting to me. I wish it had more information though. I want to know if there are tests that can be run to confirm this.

Francesca ZAMMIT CUTAJAR

7/30/2021 07:33:12 am

THANKS!! Ive just started taking B5 for post appendectomy paralytic ileus...( slowed bowel movements). Its made my digestive system move and gurgle ! I havent had gurgles in years and years. Ive always felt blocked on the motility front....never constipated..but bloating has been an issue..and..i cant go near beans! And I repeat..just no gurgles!. Id be jealous of other peoples gurgles. Im sure I had a grumbling appendix for years. I was paranoid about about eating fats when in my 20s and obsessed with fibre too...prob didnt help, but its been 3 days of 500mg B5 and im blown away by all the gurgling...!! Ive taken Neurorubine forte before ( B1,6,12 which was great for energy snd focus but never 5 on its own. Im also praying that the new gurgling " normal" me is the new me.! For always ( gurgling as I write ;-) age 56 ...life starts Now!
Good health to all of you.

Darla Petersen link

11/4/2021 02:11:55 am

Thankyou for this detailed information. You explain so well the necessity of acetylcholine in all of our systems. I am on a drug that blocks this and am having many of the mean symptoms you have explained. I will talk to my doctor about the reason for this drug and see if it really is necessary. Again, Thankyou for sharing this knowledge!!

Dr Karen Isted

11/28/2021 08:44:10 pm

What a clear and informative set of referenced articles. Thank you.

J Mati

12/11/2021 06:07:36 am

Thanks for your research Dr

Tereze

4/16/2022 11:25:28 pm

Amazing article. Makes a lot of sense and explains many of my symptoms and blood reading that I've been wondering about for years with no answers from mainstream medical practitioners. Thank you so much for posting this. You have no idea how much it helps

Pete

7/16/2022 10:17:01 am

Very thorough and informative article. I’m coming to acetylcholine deficiency as a possible cause for my cognitive and memory decline over the last 2 years from a different angle. I’m a 57 yr old male and investigations by neurologists and haematologists were unable to conclude the root cause of my problems. However, due to a sliding hiatus hernia I have been on medication for this for over 20 years. Since 2007, my prescribed medication has been 20mg twice daily of the Proton Pump Inhibitor Omeprazole. Having recently seen research articles connecting these drugs with Alzheimer’s disease I have spoken to my doctor and 2 weeks ago my dose was halved to 20mg once daily. I think (though it’s too soon to be certain) this has resulted in some cognitive improvement. I have seen somewhere that certain PPIs such as Omeprazole, while very effectively serving their primary purpose of stopping production of stomach acids, also interfere with or arrest the natural production of acetylcholine. Has your research produced any evidence of this, please? If so, is there any likelihood my memory and cognitive problems could be reversed?

Angela Potts

7/27/2022 04:44:26 pm

This article answers so many questions that I've been trying to address for years. I have low vagal nerve functioning, probably from running on adrenaline in my 38 years of nursing, and dysfunctional home life as a child.... which causes all kinds of problems. I have put in much effort in trying to raise my vagal tone, but this is the first time I've read about how acetylcholine in how it supports the parasympathetic NS. I am elated and filled with great hope in addressing this problem, I'm not even going to regret all the other money I've spent on other ways to tone the vagus nerve, since my continued search has brought me to this article! I can't thank you enough!

Dionte Williams

10/6/2022 03:57:53 am

I've been lead here after studying my diagnosis and symptoms.. Diagnosis post ganglionic cholinergic dysautonomia, symptoms: acetylcholine Deficiency ... this dysautonomia occurred after taking a tetracycline antibiotics (doxycycline) ...research lead me here, doxy inhibited protein synthesis & based on diagnosis/symptoms choline is the protein being inhibited

Sound about right to any one?

Symptoms, dry (ears,nose,mouth,eyes,skin) sun sensitivity, ibs, weight loss?

Erica Peirson

10/6/2022 09:01:29 am

Antibiotics alter the gut microbiome in a way that can ultimately alter one's absorption of certain B vitamins, especially thiamine. Antibiotics can also kill off healthy gut bacteria that make thiamine and other B vitamins for us. Choline is not a protein. It's an organic, water-soluble compound. Look up information about thiamine and dysautonomia. Here's an example.

https://www.hormonesmatter.com/artists-decades-long-dysautonomia-treated-with-thiamine/

Elaine Hillberger

10/25/2022 01:02:12 am

Exceptional article. Thank you.
I am a family physician in Sweden looking for answers. Had a full hysterectomy(resection uterus, ovaries) after problematic fibroids in the uterus and I couldn't tolerate any type of hormonal treatment for ovulation, PMS symtoms.
The most debilitating symtom was pelvic weakness which improved after resection of the uterus.
However, On HRT, low dose estradot patch, I developed myastena, successiv muscle weakness with movement/exertion,
from the jaw down to my toes, which is better with rest and in the evenings. But I have 50 % function in total.
I am on full sick leave this past year. And I plough my way through family life and healthcare, looking for solace, knowledge and experience in this matter.
I strongly suspect a connection in the neuromuscukar junction which brought me to this article. I did an EMG this summer which ruled out LEMS (Lambert Eaton) but an autoimmune reaction to the uterine myomas, attacking the healthy NM junction seems to make most sense. My doctors seem to look everywhere else. Blood tests are normal with a slight steady increase CRP, SR (inflammatory parameters)

Sudden onset menopause at 40 years of age after the operation is complex too.

If you have any thoughts, thank you. And again, I'm so impressed and grateful that many more can benefit from your hard work!
Best wishes, Elaine

Deborah Leigh Treadway link

11/6/2022 08:36:54 pm

I'm currently taking metrodonazole for constipation. I just read this article and I am so wondering if this constipation I have is due to Everyday taking Zyrtec or I don't know how long! If I were to take B5 and eat more choline Foods and stop the Zyrtec will my constipation go away?

georgia

12/22/2022 09:35:32 pm

Hello, I was wondering if supplementing with soy lecithin granules to supplement phosphatidylcholine for a strict vegetarian diet (no eggs or dairy) for an adult, what range of doses might be appropriate? One teaspoon a day? Two teaspoons? In one dose or divided? With other foods and supplements or alone?

Thank you for explaining the link to methylation cycles.

Lou Thomas

12/22/2022 10:10:10 pm

Alpha GPC (aka choline alphoscerate) is arguably the most effective source of exogenous acetylcholine, and thus can be a way of optimizing compromised cholinergic function.

Jim

12/23/2022 12:09:04 pm

One thing that stuck out to me about this article was the fact that each of those B vitamins needed to be present to create Acetyl-CoA. So would taking supplemental A-CoA be more efficient than taking B-vitamins? In my mind, this would free up the B-vitamins that would have otherwise be used to form A-CoA and allow them to be used elsewhere, much in the same way that supplemented PC eased the methylation burden. Is this accurate?

Rain Jeppson

1/7/2023 06:25:43 pm

For nearly 4 years I've been dealing with extreme hypersomnia, exercise intolerance and muscles that would fatigue easily. I've been tested for literally everything and they can't find any answers. I have been researching ACH off and on when I had enough energy and mental capacity. I finally ended up on this site and I can't tell you how grateful I am for this information. It's been only a week taking Sunflower Lecithin and Benfotiamine and my muscles are no longer a problem, my mind feels sharp and clear, my napping is much less and my overall sleep time has decreased to near normal levels. I can't wait for spring to come to jump back on my bike that I haven't ridden since June of 2019 (3 1/2 yrs. ago!) Your research and knowledge has literally given me my life back. Thank you!

Erica Peirson

1/7/2023 08:34:51 pm

Thank you so much for sharing your experience, Rain! I'm so happy this information was helpful to you. Working to optimize the production of acetylcholine has helped many of our patients as well. -Dr. Peirson

Jackie

1/30/2023 12:31:00 am

I am a post menopausal woman with a homozygous PEMT gene. Despite eating numerous eggs regularly I seem deficient in acetylcholine. Is this because of PEMT and not being able to convert dietary choline? Would taking CDP choline be my only option? Choline supplementation causes me to be pretty severely depressed so it’s a tough situation. I’ll trial the herbs you mentioned that are cholinesterase inhibitors. Thank you so much for your informative article. :)

Angela

2/19/2023 03:15:57 pm

So if choline is a precursor to acetylcholine, I feel like sunflower lecithin and choline rich foods could be a good idea. Especially with pemt genes, older people, and low estrogen.

This makes me wonder if Dysautonomia is linked to choline deficiency and PEMT genes too.

Cee link

7/30/2023 12:23:25 pm

I am so extremely grateful for you making this avail. I've been using choline (agpc or CDP) for years because of a potential choline issue. I come to this info regularly to reconfirm my understand if PEMT/coline and PPP. YOU ARE SO APPRECITED. May you be blessed with a healthy, long life for your education. Blessings Cee

Jim

6/16/2024 01:49:12 pm

Look up parasites and AchE. Multiple broad spectrum dewormers are needed and will clear the problems, along with copious amounts of kefir. Ref: Dr. Simon Yu, et al. The genetics are of the worms are changing; many, many labs will miss them, so give them as prophylactics. Copper and b12 are commonly depleted (no, the kids are not copper toxic). Modern science and genetic research isn’t applicable when there is an ongoing infection/infiltration, because the control groups haven’t been screened either. You are welcome.

Khin Maw,MD

8/1/2024 12:49:10 pm

Thank you Dr. Pierson.
You explained a complex topic in a very clear and simple manner, easy to understand. Acetyl choline is one of the most important player in memory and focus. That affects health of old and young people.
Not only in memory and focus it also explained the painful muscle spasms and jerking.
My sincere thanks for your sincere scientific article.

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