Rich van K: Choline sensitivity & Methylation | ProHealth Fibromyalgia, ME/CFS and Lyme Disease Forums

Rich van K: Choline sensitivity & Methylation

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For Rich & any other interested readers:

I've been concerned about the low level of choline in my diet due to various food intolerances & sensitivities. My average intake is about 900 mg/week (incl. 50 mg/day in multivite), while the RDA for women is around 450 mg/day.

While I would not call myself a depressed person under normal circumstances, when I've tried to increase my choline intake w/supps (phosphatidyl choline, choline bitartrate, lecithin), I've found that a single dose leaves me in a fairly severe depressive state that takes the better part of a week to resolve.

FWIW, I have a family hx of major depression, mother does best on anticholinergic ADs, son hasn't done well on any AD tried, but we have discovered he is also extremely choline sensitive -- a small dose of DMAE for example renders him practically catatonic, complete w/waxy posturing.

The biochem charts I've peeked at suggest that choline somehow feeds into or its metabolism is fed by the methylation cycle.

Pfeiffer Treatment Center (son was eval'd there) maintains that undermethylators are choline-sensitive; however son's eval results there were not a slamdunk for undermethylation.

I've tried taking choline with a little 5-MTHF (200 mcg. folinic acid), but no improvement in tolerance.

Any comments or suggestions? Thanks.



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Hi, SnooZQ.

I think you have raised a very interesting subject.

As you probably know, choline comes partly from the diet, and part of it is made in the body. The connection with the methylation cycle is that it is thought that the second largest use of methylation in the body (after the synthesis of creatine, thought to be number one) is the conversion of phosphatidylethanolamine to phosphatidylcholine. Phosphatidylcholine is an important phospholipid, making up the cellular membranes. It is also an important component of bile.

Some of the phosphatidylcholine is broken down, and the choline used for other purposes. A major one is the synthesis of acetylcholine. Acetylcholine serves as a neurotransmitter in parts of the brain, it serves as the neurotransmitter between the nerves and the muscle cells, and it serves as the neurotransmitter for the parasympathetic nervous system in general.

In chronic fatigue syndrome, it is my current hypothesis that choline, phosphatidylcholine, and acetylcholine are depleted. I realize that some of the magnetic resonance spectroscopy studies have concluded that choline is elevated in the brain, but I think this conclusion was based on a faulty assumption. In these studies, the ratio of choline to creatine was found to be higher than normal. It was assumed that creatine was unchanged between normal, healthy people and PWCs, so the conclusion was that choline was elevated. However, because of the partial methylation cycle block, I think we should expect that creatine is depleted in CFS, and if it is depleted more than choline is depleted, the ratio would be higher than normal, even though both these substances were depleted.

I expect that there will be an MRS study coming out soon that will report on absolute measurement of these metabolites, rather than simply ratios, and I expect that it will show that choline and creatine are both below normal in CFS.

I think that low acetylcholine would explain the results of blood flow studies in the forearm reported by Vance Spence's group at the U. of Dundee a few years ago. I think it can also help to explain why the ratio of sympathetic to parasympathetic nervous system activity in CFS is higher than normal, as shown in heart rate variation studies.

The assumption of constant creatine has carried over to the use of creatinine ratios in urine testing of various metabolites. The assumption of constant creatine to creatinine conversion rate has justified this practice for compensating for differences in urine dilution by water. Normally this is fine, and the creatinine production correlates with lean muscle mass, but is otherwise a constant. But in CFS, we see drops in 24-hour creatinine excretion in urine, and I think that is consistent with the partial methylation cycle block.

So that's the situation as I see it in CFS in most cases, and I'm hopeful that it will be borne out by work now underway.

Now, getting to your case, it sounds as though you have an unusual response to choline supplementation. Elevated acetylcholine in the central nervous system can cause depression. My guess is that your body may overproduce acetylcholine, or it may not be able to break acetylcholine down as rapidly as normal, and one or the other of these may account for the depression on supplementing choline. This sounds like a genetic issue, given the experience of your mother and your son as well. The rate-limiting step in the production of acetylcholine in the neurons of the central nervous system is the transport of choline into the neurons. The breakdown of acetylcholine is accomplished by the cholinesterase enzymes.
So I suspect that you may have inherited a genetic polymorphism that speeds up the action of the choline transporters, or a genetic polymorphism that slows the action of one of the cholinesterases.

You asked for suggestions. A couple of things you might consider are having a heart rate variability study run to see how balanced your sypathetic and parasympathetic nervous systems are. This is an easy thing to do. Basically it's an electrocardiograph with a computer associated to analyze the heart rate data over time, and it will tell whether the sympathetic or parasympathetic system is dominant, or whether the autonomic nervous system as a whole is not working well.

Another thing you might consider is to have an analysis run for acetylcholine. I know the Health Diagnostics and Research Institute (formerly Vitamin Diagnostics) runs this test. Taken together, these tests might help you to sort out what's going on.

Beyond that, a genomic analysis, such as is offered by companies like 23andme might reveal polymorphisms in the choline transporters or the cholinesterases.

These sorts of studies might help you to pinpoint what's happening.

As to what can be done if the acetylcholine level is too high, you are probably aware of scopolamine, which blocks muscarinic acetylcholine receptors, including in the central nervous system. I don't know if that would help you or not, but it's something to look into.

I have not been able to reconcile the Pfieffer Center's concept of over- and undermethylation with what is found in people with CFS, so I haven't found it to be useful.

Best regards,

Rich[This Message was Edited on 07/17/2010]


New Member
You've given me a lot to think about, Rich. I had no idea that the tests you mentioned were available.

Since the effects of even a relatively small amt of supplemental choline seem to be so long-lasting, I'm wondering about the acetycholinesterase aspect. Not sure if it's related, but I am very sensitive to nightshades in all forms (including second-hand smoke). It does not appear to be a typical IgE allergy (have been tested). Apparently nightshade plants inhibit acetylcholinesterase.

I'm not sure about my ANS balance, however do know that I am prone to some sort of hypotensive tachycardia, which my doc presumes to be mild AF. From my own observation I conclude that it is more likely adrenal-related, since even a very low dose of hydrocortisone aborts the tachycardia.

Unfortunately we did not find the Pfeiffer TC analysis terribly helpful either, except in one respect. They uncovered our son's extremely low (not detectable) glutathione metabolites, a possible explanation for his lifelong chemical sensitivities & the surface scalloping present on his brain SPECT scan, which is supposedly indicative of either alcoholism (not a factor) or toxic exposure.

Thanks again. I always appreciate your thoughtful insights.
[This Message was Edited on 07/17/2010]


New Member
Have you tried getting choline from foods? Maybe it wouldn't affect you the way a supplement does. 1 egg has about 100 mg of choline. It's in the yolk.


New Member
Thanks for your suggestion. It is a good one for many people.

I know egg yolk is a great choline source, however I have a life-long egg allergy. Certain dairy products contain choline, but have dairy allergy. I am very sensitive to soy, peanut & several other legumes, which are good choline sources. Cauliflower is a good choline sources (for a veg), but if I consume more than an average serving (well-cooked only), my thyroid function is affected & I suffer.

Perhaps if as Rich suggests, my body excels at making its own choline, or if it is very sluggish at breaking down acetylcholine, maybe my choline intake requirements are less than that of the average person ...

[This Message was Edited on 07/19/2010]