Acetylcholine/Choline Deficiency in Chronic Illness – The Hunt for the Missing Egg

ucm278430We hear a lot about vitamins and minerals such as B12, folate, magnesium, vitamin C, and so on, but there seems very little talk these days on the importance of dietary lecithin and choline. Are you consuming an adequate amount of acetylcholine, or other phospholipids? The odds are that you are not.

A little bit about choline

The human body produces choline by methylation of phosphatidylethanolamine (from dietary sources such as lecithin and others) to form phosphatidylcholine in the liver by the PEMT enzyme. Phosphatidylcholine may also be consumed in the diet or by supplementation. Choline is oxidized to betaine which acts as an important methyl donor and osmolyte.

For those wanting to see how this relates to the methylation cycle, below is a nice graphic (courtesy of Wikipedia).

Choline metabolism

It is well known that magnesium deficiency is widespread (57% of the population does not meet the U.S. RDA according to the USDA), but the numbers for choline deficiency are even more shocking.

According the National Health and Nutrition Examination Survey (NHANES) in 2003-2004, only about 10% of the population have an adequate intake of choline. This means about 90% of the population consumes a diet deficient in choline. Furthermore, those without an adequate intake of choline may not have symptoms.

Along with folate and B12 deficiency, inadequate consumption of choline can lead to high homocysteine and all the risks associated with hyperhomocysteinaemia, such as cardiovascular disease, neuropsychiatric illness (Alzheimer’s disease, schizophrenia) and osteoporosis. Inadequate choline intake can also lead to fatty liver or non-alcoholic fatty liver disease (NAFLD).

The most common symptoms of choline deficiency are fatty liver and/or hemorrhagic kidney necrosis. Consuming choline rich foods usually relieve these deficiency symptoms. Diagnosing fatty liver isn’t as simple as running  ALT and AST since nearly 80% of people with fatty liver have normal levels of these enzymes according to a population study published in the journal Hepatology. In fact, in an experiment, 10 women were fed a diet low in choline. Nine developed fatty liver and only one had elevated liver enzymes.

For those who are genotyped by 23andMe, there is a SNP (rs7946) related to NAFLD you can look at in the PEMT gene called PEMT G523A (V175M). Caucasians with nonalcoholic fatty liver are more likely to carry the rs7946 (T), with the effect being most pronounced for rs7946(T;T) genotypes. [PMID 16051693]

If you are genotyped by 23andMe, make sure you are logged in to 23andMe and you will see your results for this SNP.

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Choline, the nervous system, and the heart

Despite it’s role in the CNS and stimulating parasympathetic activity, there is very little info about choline and mental illness. However, in a large population-based study published in The American Journal of Clinical Nutrition, people with higher blood levels of choline had lower levels of anxiety – however, levels of choline did not correlate with depressive symptoms.

Despite the lack of studies, it has been clinically observed that supplementing Lecithin or putting patients on a Lecithin rich diet can lower levels of anxiety, help the nervous system by establishing balance between sympathetic and parasympathetic, and even manage cardiac dysrhthmias. The Milner Acetylcholine Protocol (MAP) uses lecithin to manage cardiac dysrhthmias.

Phospholipids and the cell membrane

The fundamental building blocks of all cell membranes are phospholipids. Lecithin consists of phospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, Phosphatidic acid, other minor phospholipids and glycolipids. About 50% of the mass of most cell membranes are composed of phospholipids. The plasma membranes of cells also contain glycolipids and cholesterol – which correspond to about 40% of the total lipid molecules. Adequate intake of phospholipids and glycolipids is important for the integrity of the cell membranes. Lecithin contains a balanced amount of phospholipids and glycolipids.

Phospholipid supplementation has also been shown to help with mitochondrial dysfunction in patients with diseases such as Chronic Fatigue Syndrome, chronic Lyme Disease, Fibromyalgia, and Gulf War Illness. Fatigue reduced about 40% in Chronic Fatigue Syndrome patients after lipid replacement therapy (supplementing phospholipids) according to the Journal of Chronic Fatigue Syndrome.

Adequate intake of choline and choline-rich foods

Adequate intake of choline varies by age. Here is a table by CholineInfo.org.

Adequate Intake (AI) levels for choline are:

Population

Adequate Intake (AI)
of Choline

Infants:(0-6 months)
(7-12 months)
125 milligrams
150 milligrams
Children:(1-3 years)
(4-8 years)
(9-13 years)
200 milligrams
250 milligrams
375 milligrams
Adolescents:(14-18 years)400 milligrams (Females)
550 milligrams (Males)
Adults:(19 and older)425 milligrams (Females)
550 milligrams (Males)
Pregnant women450 milligrams
Breastfeeding women550 milligrams

CholineInfo.org also has a very nice graphic showing the best sources of choline. According to their chart, beef liver and egg are by far the best sources for lecithin with modest amounts in lean beef, chicken breast, cod, wheat germ, and cauliflower.
cholne-chart
Unfortunately, not all nutrition data is the same, and for the sake of comparison, below is what Wikipedia lists as high choline foods.

Animal and plant foodsCholine (mg)Calories
32 gram sunflower lecithin syrup544250
5 ounces (142 g) raw beef liver473192
15 gram soy lecithin granules450120
A cup of wheat germ202432
Half a pound (227 g) cod fish190238
A pound (454 grams) of broccoli182158
A pound (454 grams) of cauliflower177104
Quart of milk, 1% fat173410
Half a pound of chicken150543
Two cups (0.47 liters) firm tofu142353 
A cup of uncooked amaranth135716
30 gram Brewer’s yeast (2 tbsps)120116
A cup of uncooked quinoa119626
100 grams of Soybeans dry116268
Large hardboiled egg11378
A pound of spinach113154
Two cups of cooked kidney beans108450
A cup (146 g) of peanuts77828
A cup (143 g) of almonds74822
Three cups (710 cc) cooked brown rice54649
A grapefruit19103

Since cooking eggs at high temperatures destroys the choline content, it’s best to cook the egg so the yolk is runny to preserve lecithin content. For people without egg allergies, properly cooked eggs is one of the best sources of lecithin.

In presence of an egg allergy, consuming liver or supplementing with sunflower lecithin may be the best options to ensure an adequate intake of choline. Sunflower lecithin may be a better source for lecithin than soy because unlike soy lecithin, sunflower lecithin is never derived from GMO crops. Also, soy is generally more allergenic than sunflower, so soy lecithin could potentially provoke unwanted effects in sensitive individuals.

Acetylcholine, phospholipids, autoantibodies, and a word of caution

Acetylcholine and antiphospholipid autoantibodies are seen in various autoimmune and chronic illnesses. It is well know that with Myasthenia Gravis, patients most commonly have autoantibodies against nicotinic acetylcholine receptor (nAChR). A large number of CFS patients may have acetylcholine receptor antibodies according to a study published in the International Journal of Molecular Medicine.

Dysautonomia and POTS can also be associated with autoantibodies against acetylcholine receptors. Mayo medical laboratories has a very comprehensive Autoimmune Dysautonomia Evaluation lab test that tests for autoantibodies against acetylcholine receptors and much more.

Antiphospholipid Syndrome (or Hughes syndrome) is an autoimmune condition that can lead to hypercoagulation and blood clots. Conditions such as Lupus, Sjogren’s syndrome, Chronic Fatigue Syndrome, and Fibromyalgia are often associated with antiphospholipid antibodies. Antiphospholipid antibodies can even develop in presence of chronic infections such as Hepatitis C, Syphilis, Chlamydia pneumoniae, EBV, HHV-6, Lyme disease, mycoplasma, Q Fever, and many other infections. Antiphospholipid syndrome can be tested for with LabCorp’s Thrombotic Risk Profile.

At this time there is insufficient evidence to determine if supplementing lecithin would be beneficial or harmful for those with acetylcholine receptor autoantibodies or antiphospholipid syndrome. More clinical research is needed to understand how lecithin supplementation influences the various autoimmune processes that may exist in these patients.

Whether you are a health expert with experience utilizing choline rich foods or lecithin supplements to treat chronic illness, or a patient using choline to promote your own health, please share your experience below.

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Melissa
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Melissa

This article was particularly interesting to me as I have been diagnosed with Lyme and CFS in the past and also have Myasthenia Gravis, POTS/Dysautomnia as well as heterozygous for the MTHFR gene, which I’ve begun to suspect plays a role in my diseases and perhaps this as well. Thanks for the valuable info!

Susan
Guest
Susan

Thanks for the good information. You may also want to add some information about cystic fibrosis and choline. There’s been some interesting papers from British Columbia on this topic. Thanks for the reference to the papers on chronic fatigue. Very helpful.

MK
Guest
MK

I have several biggie mutations in the methylation cycle and have been on various vitamins and supplements for several years with mixed results. I started on 1 Tbsp per day of liquid soy lecithin back in the spring, and there was an almost immediate and very noticeable difference in my anxiety level, chronic constipation, and focusing issues. Despite being in the gifted program as a kid and having a high IQ, I have always been frustrated with my attention level and ability to finish what I start (didn’t finish HS on time, dropped out/kicked out of college multiple times 10… Read more »

Shae
Guest

I have Dysautonomia (hyperMCAS POTS and NCS/NMH) plus a host of comorbid conditions. I am a ‘no call’ on this allele. Any suggestions?

Shae
Guest

I love eggs. Unfortunately, I’m a complicated zebra…I can’t take the typical Meds, and have unfortunate comorbidities. Kinda hosed, basically. I’m also hyperMCAS POTS (extremely rare subset of hyper POTS) as well as NCS/NMH, so it gets complicated, indeed. I know several of my COMT SNPs carry mutations.

Tiffany
Guest
Tiffany

I got a prenatal diagnosis of trisomy 21 for my last child and read a study in a mouse model of T21 where pre- and perinatal choline improved symptoms. I started 3 g/day choline at ~20 weeks and my now 8 month old was born with no major health issues and is progressing age appropriately in terms of meeting milestones. We have continued choline during breastfeeding. I would love to find out the level of methylation on my son’s 21st chromosome as I’m sure that the high dose choline has decreased the severity of effects from the additional chromosome.

melvin
Guest
melvin

the snp you named above for pemt is the one my results say is the normal one TT and shows green not red colored like the mthfr.

Why would the wild type normal be a higher risk for fatty liver?

James
Guest
James

Great article but I think there is an error.

We are only interested in the raw egg yolk portion of the egg which would be about 17 grams. This means there is roughly 116 mg of lecithin per raw egg yolk and not 389 mg.

john
Guest
john

I am diagnosed with myasthenia gravis.and undergone post thymectomy. Can I use this lecithin as a supplement. Will I see any improvement in my situation. Thanks in advance.

Kathrynn
Guest
Kathrynn

I have been having some intermittent ptosis (eyelid drooping) and myasthenia gravis was suggested as a possibility. I put together several conversations about myasthenia gravis with a word I remembered from my detox report “acetylation”, so I ran my 23andme results for PEMT and I am +/+ homozygous TT for the rs7946 and also rs4646408 is +/+ TT as well. Of the rest of the PEMT there are 22 heterozygous, 10 normal, and 13 not genotyped. According to my detox report I am probably a slow acetylator since I have NAT2 R197Q rs1799930 AA +/+. Also in the detox report… Read more »

Christi
Guest

I’m hoping to connect the dots between this and BCHE gene rs1799807, cholinesterase inhibitors, nightshade intolerance. Anne Wright has written on it.

I’ve had a decrease in POTS like symptoms, mysthenia gravis like symptoms, CFS/Fibromyalgia, just from eliminating Nightshade foods.

I like eggs but they seem to make me sick to my stomach, I wish I could benefit from a choline supplement I still have anxiety and memory problems.

Dan
Guest
Dan

HI Christi, I’m not a doctor, but a patient like you. I’ve also found that I need to avoid nightshade foods big time or I get muscle cramps, twitching, and just overall overstimulation. High acetylcholine levels can cause anxiety as well due to that overstimulation. I recently found a study that showed a connection between B12 deficiency and low acetylcholinesterase levels, suggesting that perhaps B12 may help increase the breakdown of acetylcholine. The same with l-carnitine. Treatment with l-carnitine helped restore acetylcholinesterase levels in aged rats. Not sure if the same thing occurs in humans, but it’s worth noting that… Read more »

David
Guest

No discussion about choline, phosphatidylcholine or lecithin (or even L-carnitine, betaine or TMG) consumption is complete without a thorough discussion of TMAO (Trimethylamine N-oxide).

There are several studies on this subject. Here is one:

Gut flora metabolism of phosphatidylcholine promotes cardiovascular… – PubMed – NCBI
http://www.ncbi.nlm.nih.gov/pubmed/21475195

As far as popular media, Dr. Oz, who used to recommend L-Carnitine supplements, has retracted that recommendation. When it comes to TMAO, there is little difference between L-Carnitine and choline supplements.

Joel Greene
Guest
Joel Greene

I have acetylcholine esterase deficiency. My C-reactive protein test was “7”. Do I have a higher level of inflammation or does this mean that a serious health telatefevent is imminent?

fd
Guest
fd

well, thank you so much Researcher. The information was a lot and it took me some days to read and study all, but it was worth it.

Terry Lynch
Guest

Thanks so much for the treasure chest of Lecithin and acetycholine interactions and preponderant choline deficiency pathophysiology. Recently a multifocal motor neuropathy(less than 4000 diagnosed US) case showed up in my neigborhood falling over from left sided muscle deterioration. She had been taking IgA twice a month with a present cost presently exceeding $20,000 / month since 1990. Within 6 months on a proper choline rich diet, stress free gardening in a peaceful place, and one tablespoon of granular Lecithin (always purchased direct from manufacturer and kept in the freezer to avoid oxidation!!) her neurologist in NY was flabergasted, astonished,… Read more »

Research
Guest

B Vitamins and Folic Acid cannot replace inadequate Choline, these may increase the volume of Homocysteine recycling into Methionine and it is possible that these are complicating factors. Physiology prefers its energy as Hydride fracked from Choline and Methyl Groups, producing ATP from these. The reason sugar is so pleasing and sweetness of sugar is correlated to Hydride content of sweeteners and molecules. Obtaining meals without adequate Choline results in a net decrease in Choline because Choline is required to produce Digestive Fluids through the activity of MDR2. The answer is choline, protecting PEMT from being in inhibited and the… Read more »

Terry Lynch
Guest

Researcher, I am very grateful or your metabolic treatise! I will be studying your profound observations until my dying day(maybe not so fa of at my age of 67.)

Dan
Guest
Dan

“A Researcher”: The info you have provided (and provided and provided and provided) is OVERWHELMING, and impossible to wade through.

Please try and make it ‘user-friendly’ to the average reader.

Thank you.

Chris
Guest
Chris

For those struggling with B12 deficiency, I recently heard about a new oral prescription alternative to the injections called Eligen B12. I recently read that it works even if you don’t have intrinsic factor (so even if you don’t have normal gut absorption). Apparently it came out a month or two ago. Has anyone heard of it or tried it??

Tomm
Guest
Tomm

It has a lot to do with nicotinic acetylcholine receptors like alpha 7 NAchR. It is involved in inflammatory pathways more than you would think.

Even patents for treating chronic disease with AChEI natural drugs like galantamine exist – http://www.psoriasisdietplan.com/2014/08/patent-application-published-in-2006-describes-effective-treatment-for-many-chronic-diseases/

That’s why smoking may help lose weight, alleviate arthritis, improve cognition, etc… or do right the opposite.

Huperzine A, Galantamine, lecithin, DMAE, …. and B-vitamins due to their importance in making the acetylcholine like B1 – thiamine.

steve
Guest
steve

What about Egg Lecithin?
I use the Capsules from Nature’s Plus

David Clark
Guest
David Clark

I found the site: http://amehsi.org/. And all I have to say is, wow, what a lot of information to take in. I have been having strong symptoms along these lines for a few years (I am 51 now). I also now realize that I may have had milder symptoms since being a child (particularly chronic diarrhea and trouble swallowing certain foods). I have only in the last few days, however, realized that I may be dealing with one of the myasthenic syndromes probably congenital (I am aware of a couple others in my family who have died of symptoms similar… Read more »

Garry
Guest
Garry

The achr-ganglionic autoantibody was found in my blood several years ago. Is there any new news on choline supplementation if you have this condition?

Margie
Guest
Margie

I have primary biliary cirrhosis, nafld, sjogrens , pulmonary fibrosis, hashimotos. Went into remission but developed myasthenia gravis and menieres anyway. Am on mestinon. It is positively affecting my fatty liver, the fat seems to be finally getting better. I have always done better on vitamins with more choline and was in l carnitine while I developed the mg. U believe choline and supporting vitamin supplementation could be an effective treatment for fatty liver. The mestinon also helps with mental clarity. Mestinon increases acetylcholine. Tramadol or a derivative I think will be important also in treating autoimmune diseases because of… Read more »

Alessa
Guest
Alessa

Thank you for this very informative article. I recently had stomach issues and stopped all my supplements. That was two weeks ago and now my symptoms are bad. I have Sjogren’s and Hashimoto’s and I am in a huge amount of pain, have dry eyes, sore throat, and neck feels like it needs a chiropractor every day. I restarted my fish oil supplement yesterday and will restart lecithin today. I didn’t realize how bad things could get without it. As a sidenote, I also have CFS, depression, anxiety, and am extra sensitive to pain. I carry MTHFR but not sure… Read more »

Jade Edward
Guest
Jade Edward
Marcia Lester
Guest
Marcia Lester

I have Myasthenia Gravis, Hashimoto’s thyroiditis, Sjogren’s, and my dysautonomia was finally diagnosed. My infertility was caused by endometriosis(autoimmune), and, an endometrial receptor cell defect. MG is also a receptor cell defect. My neurologist, informed me, that MG with dysautonomia wasn’t unusual. Having trouble swallowing food, doctors diagnosed me with achalasia, related to my MG. I, also have common variable immune deficiency syndrome. Following, a second bout of thrombophlebitis, I was tested for anti-phospholipid syndrome and everything came back normal. Doctors felt the thrombophlebitis was secondary to taking b.c. pills and hormones. My B12 levels became elevated after I took… Read more »

Research
Guest

Get curcumin, Berberine, S Methyl Methionine and Grape Seed Extract. Also cover up the power outlets in your dwellings with tape and purchase EMF protection blankets, curtains and stickers. Focus on making sure that PEMT is function, Sulfur is available, use molybdenum to manage the sulfur if the literature about sulfur toxicity makes you uncomfortable, Methylsulfonyl Methane is beneficial but its usually applied for conditions affecting bones and other conditions. phosphatidylcholine, zinc and 6s 5678 Tetrahydrofolate, and NAD+ as well as nucleotide supplements should put these conditions out of operation. Alway, work these through with your clinician.

Ngasha
Guest
Ngasha

I have Ulcerative Colitis, Fibromyalgia, Asperger’s & MDD. I am presently (3/2017) in a double-blind study for Protect-3 phosphatidylcholine granules from soy lecithin in the treatment of U.C. It’s going good, I think I have the real thing, much improved!

SOCS
Guest
SOCS

Hi. Great info. Thanks all. Wondering the specific test names or test #’s for Labcorp and others you’ve mentioned. It’s so easy to end up w/ the wrong test, they have so many!

Lilac
Guest
Lilac

Choline can also make people very depressed, because it can lead to excess of the neurotransmitter acetylcholine. That is known to cause depression, and new drugs are being developed that block excess acetylcholine in the brain. See for example the work of Yale researcher Marina Picciotti. The body uses dietary choline to make acetylcholine. On the genetic side, some persons have a mutation in the BCHE gene (rs 1799807), which leads to a shortage of the enzyme “Butyrylcholinesterace,” which breaks down acetylcholine as well as other chemicals with choline. Thus this enzyme may lead to having excess acetylcholine, and one… Read more »

DebKlausing
Guest

You need of a supplement with phosphatidylcholine that is not in a pill form so it does not have to be digestive through the distractive digestive system with minimal absorption and therefore minimal effects. Phosphatidylcholine should be in the form of a liposome in order to have a 90% absorption rate for full benefits of phosphatidylcholine via the Liposome technology. Microlife nutritionals was developed by Dr. Emek Blair and became available to purchased January 2017 dklausing.vasayo.com for more information.

Mathew Carnage
Guest
Mathew Carnage

Nice article and thank you for the information. I knew about choline deficiency from here: https://www.xcode.life/23andme-nutrition-raw-data-analysis I didn’t realise that it had so much underlying genetics to it.

OrganisedPauper
Guest
OrganisedPauper

I have several genetic factors that collide. More than one that affect the synnthesis of choline, meaning I’m likely to be deficient, and one that lowers the production of phosphotydilecholine. But, I also have more than one genetic factor which means saturated fat increases obesity and type diabetes and other health problems. Most sources of choline seem to come with a dose of saturated fat. As I need more choline than most people, and possibly betaine I’m not sure what to do. I have found saturated fat makes me feel quite ill. I already have Bipolar, diabetes, Fibromyalgia and possibly… Read more »

teri
Guest
teri

I have hereditary alpha tryptasemia- extra tryptase genes. It lends to MCAS, Dysautonomia, and connective tissue issues. The drugs that help with the MCAS is ketotifen (a mast cell stabilizer)- which is a strong muscarinic receptor antagonist (so I have read) which would be a acetylcholine blocker. Trying to wrap my brain as to how this fits in. I was noticing more Dysautonomia symptoms of shallow breathing, etc, so trying to find alternatives to the ketotifen. Thank you so much for this study….

Research
Guest

Choline deficiency, Hydride Inaquacy, PEMT inhibition and Homocysteine independently enable, cause and exacerbate every nuance of this disease and every other disease

InterestedRsearcher
Guest

According to the empirical data and the Amehsi.com website, each of the health conditions on this web page, including Genetic Conditions, should be considered as deficiency until the primary deficient pathways causal to detrimental Human outcomes are beneficially managed. Review the Amehsi Specification at Amehsi.com The factors to manage are Choline is required at 4mg per KG of Anatomical Mass each day or betwen 800 and 1326 mg per day for Human Adults. The dosage for other organisms or developing Humans should use the mg/mass guideline. Homocysteine whould be managed to below 7 Micromoles per liter. (Dimetylacetothetin, S-methylmethionine, Trimethylglycine, Folate,… Read more »

Jason
Guest
Jason

Does it strike anyone as amazing that the American diet is end loaded with Beef Chicken and Eggs and yet only 10% of the population has adequate choline intake? How is this possible?

Thomas Thibault
Guest
Thomas Thibault

This can’t be true because you would need to eat more than 6eggs everyday, or 800 Gr of meat or 1kg of vegetables.. For have the adequate amount. Wich would be probably more harmful than beneficial. The suggest amount are impossible to get with any normal diet.
I also doubt the amount of lecithin you would need, I found totally other numbers

ursula caballero
Guest
ursula caballero

Hi,
Thank you ALL for such vast information.
I have a gene mutation at the CHRNA 2, 4 and CHRNB2 receptors for acetycholine. It is an autosomal dominant transmission mutation which causes me Nocturnal Frontal Lobe seizures, and many other symptoms related to the vagus nerve.
I would like to try Alpha GPC and L Serine to help with the chronic insomnia. I’m a bit nervous adding something to my brain function, since i react differently to many supplements and medications.
Any thoughts?

Researcher
Guest

Consider every genettic condition as a metabolic syndrome until you get between 4 and 7 mg of choline per kg of anatomical mass, 500 mg of s-methyl methionine using gastromendhp, nad+, 500 mg of methylsulfonylmethane, 300 mg of grapeseed extract, 500 mg of l-arginine, 500 mg of mixed rna/dna nucleotides, 500 mg of ribose, 1/4 tablespoon of pink himalayan sea salt, no typical table salt, only filtered water, amineral supplement including alkali minerals, zinc, molybdenum, all b vitamins with methyl cobalamin. 5678 methyltetrahydrofolate is the best filate to include. You also must cover up the power plugs and outlets in… Read more »

Researcher
Guest

Using the Amehsi Website, you and your provider should be able to determine an effective therapeutic path for any health status.