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.

By geneticgenie | October 21st, 2013 | Posted in Uncategorized |

16 Responses to “Acetylcholine/Choline Deficiency in Chronic Illness – The Hunt for the Missing Egg”

  1. Melissa Says:

    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!

  2. Susan Says:

    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.

  3. geneticgenie Says:

    Susan – If I were to include all info there is about choline, I might as well write a book. But interesting note about cystic fibrosis. A little research shows that they can have high homocysteine and tend to have low glutathione too. And choline can improve homocysteine and glutahtione in cystic fibrosis patients. There is a lot of talk about using B12 and Folate to reduce homocysteine, with not as much talk about how prevalent choline deficiency is. Choline lowers homocysteine. And like folate, it turns into an important methyl donor when it is oxidized into betaine.

  4. geneticgenie Says:

    Interesting history Melissa. Were you ever tested for acetylcholine receptor autoantibodies or antiphospholipid antibodies?

  5. MK Says:

    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 years ago). I am now taking college classes and getting all A’s. In the middle of summer semester I ran out of lecithin and kept meaning to pick some up and didn’t really make it a priority, but for the 2 weeks I was off of it I would just sit in front of the computer, unable to complete the papers I had to write. That spaciness and lack of focus went away as soon as I restarted the supplement. I’ve tried citicoline and a normal choline/inositol supplement, and they both made me nutty. Lecithin doesn’t do that. Tastes like crap and the texture is nasty but I can choke it down if it gets me through school. : )

  6. Shae Says:

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

  7. geneticgenie Says:

    Shae – A no call for that gene probably means that 23andMe had trouble genotyping that part or area of your DNA. So there are no conclusions you can draw from that.

    However, it’s just a single gene and it’s not determinant of fatty liver or choline deficiency. It just increases odds of developing fatty liver which can be caused by choline deficiency.

    I don’t give medical advice, but do you eat eggs? Some may do well with them, some potentially worse depending on autoantibodies and allergies. Nevertheless, most otherwise healthy people do not get enough lecithin as described in the post.

    POTS can be caused by acetylcholine dysregulation and acetylcholine receptor antibodies and many other things. What to do in that case isn’t clear to me, but a good POTS specialist (found at dinet.org) usually knows how to test for these things and what to do about them.

  8. Shae Says:

    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.

  9. Tiffany Says:

    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.

  10. melvin Says:

    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?

  11. geneticgenie Says:

    First, the wild type isn’t always beneficial. Second, it is the wild type for caucasians, but not for most other ethnicities.

    http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=7946

    Digging a bit more before this comment, it doesn’t appear that there is universal agreement that this SNP increases risk of NAFLD. However, caucasians with NAFLD appear to be more likely to be TT. Confusing indeed!

    http://www.fasebj.org/content/19/10/1266.long
    http://www.fasebj.org/content/20/12/2180.long

  12. James Says:

    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.

  13. geneticgenie Says:

    James – thank you for your correction. Will correct the article.

  14. john Says:

    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.

  15. Kathrynn Says:

    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 are CYP1B1 L432V rs1056836 GG +/+ and CYP1B1 N453S rs1800440 CC +/+ but I’m not sure if that has an impact on acetylcholine or not. Myasthenia gravis is an autoimmune disease. In myasthenia gravis, antibodies block, alter, or destroy the receptors for acetylcholine at the neuromuscular junction, which prevents the muscle contraction from occurring. I have autoimmune diseases already which automatically makes me susceptible to others.
    Am I correct in thinking that these gene defects regarding acetylation would mean that I have less acetylcholine in the first place? If so it would seem to me that antibodies further blocking receptors for what little there is might bring on symptoms or exacerbate them.
    I was having an episode of ptosis yesterday and I find it interesting/strange that I had a craving for fried eggs with runny yolks. I ate 5 of them. The ptosis went away later that evening. I hadn’t read your article at that time but now I wonder if it was my body craving the lecithin for the choline? Also, I happen to have choline bitartrate powder… would that be beneficial to take or not?

  16. Christi Says:

    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.

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