Q for George N re PB/choline

Hi George,

Over on another current thread ' Flu, Afib, Lyme Disease, ‘True’ Colloidal Silver', and in response to my posting thereto, Erling stated:

"I followed the PB discussion out of curiosity and ignorance, while puzzling if this anticholinergic would inhibit the potent methyl donor choline, a major player in Dr. Cooney's methylation package. He notes that choline is best taken early in the day if one has difficulty with sleep, because of its part in the neurotransmitter acetylcholine. In other words, would choline be contraindicated for someone with 'vagal' AF?"

In acknowledgement of your invariably knowlegable and incisive thinking, I'd be very interested to know what your take on Erling's statement is George.

Kind regards,

Mike

Hi Mike,

I don't have an immediate answer for you. Will require some study. I'm traveling right now, so may be a bit before I look at this. Interesting question, though.

George

Hi George,

Hope you are enjoying the travelling and look forward to hearing from you when you get back.

Cheers,

Mike

Thanks Mike,

Yes, I was just reflecting on my unusual habits. In addition to a bunch of supplement pills, I have several bags of white powder & crystals that I hope are not questioned at security (taurine and mag chloride). Then I stop by the nearest market and pick up CO2 water and magnesium hydroxide (milk of magnesia), chill the CO2 water and proceed to make some Waller Water. I also make up two liters of mag chloride water, from my crystals.

I've been working on some projects in parts of the world without some of the first world conveniences, along with a bit of additional risk. I've reflected on the fun I'll have, if I end up having to travel to these places. Just adds to the challenge.

Cheers,

George

Hi Mike,

Dr. Cooney's comment was not specific to choline (my memory was off), but rather to methyl supplements in general. It seems reasonable that this overall effect might be attributable specifically to the choline, as precursor to acetylcholine (this is beyond me). In any case, your question specific to choline does seem appropriate. Here is his comment, from Methyl Magic, p. 70:

"In general, methyl supplements tend to increase alertness and wake you up when you may want to sleep. So it's a good idea to take methyl supplements in the morning rather than at night. People who already have trouble sleeping should consider this before taking [methyl] supplements..."

Erling

Mike - check out the function of choline here...many examples with a Google search:
[www.whfoods.com]

Before my ablation, I took fairly large amounts of choline in the form of phosphatidyl choline and I was not aware that it contributed to my afib which was vagally mediated.

Jackie

I just now having checked my cupboard realised that I am, in fact, currently (and have been for the last couple of months - as part of my Hc lowering regimen) taking 'Source Naturals, Inositol & Choline, 800 mg, 100 Tablets'. I take it in the mornings with no problems so far.

Jackie, do you still take the phos choline and, if not, why not?

Regards,

Mike

Mike - Yes - I still do take Phos choline with meals to aid with fat absorption. Jackie

Mike,

One PB question I had relayed to Dr. Reiffel was about PB and dementia caused by anticholinergic meds. In theory, PB doesn't cross the blood brain barrier, so should not be an issue. However, since I have a mother with dementia, it would be a big negative if PB has a causative effect. I've not gotten a response. A google search certainly shows that choline can offset the mental issues caused by anticholinergics.

In my case, I eat 4 large eggs/day. According to some sources, there are 113 mgs of choline/egg, so 452 mg choline/day from this source for me.

I eat them at breakfast. I've not seen any negative effect from this regarding my vagal afib. Quite the contrary - as long as I keep up my high levels of magnesium intake, my heart is quite stable.

One of my more sensitive indicators - even more-so than my recording monitors - is the my very vagal time immediately after sexual climax. I can feel my heart "pounding" and at the same time dramatically slowing down. When my magnesium, potassium and taurine are not optimal, I can feel ectopic beats during this time. When all are optimal, the ectopic beats are nowhere to be found. I can still feel the pounding and slowing, but it is all quite regular. The ectopics can be disconcerting, the regular beat quite comforting.

As background, here is a paper relating acetylcholine and vagal afib.
[www.tsoc.org.tw]. PB is propantheline bromide. Dr. James Reiffel has used a protocol including PB to successfully treat vagal afib. PB is an anticholinergic med. Dr. Reiffel has published on his approach. For more on this topic, here is a search on the last board [www.afibbers.org]

The question Mike is asking is "does intake of choline increase acetylcholine in the system and therefore increase the propensity for vagal afib?"

It is a question I do not have an answer for.

George

So in the referenced paper above, [www.tsoc.org.tw]

... selective specific GIRK channel antagonists could be useful in the treatment of AF. In GIRK4- knockout mice,43 vagal AF is prevented without favoring ventricular arrhythmias or affecting AVN function. Therefore, GIRK blockers are potentially therapeutic without adverse effects on ventricular arrhythmia or conduction. However, the sinus rate might be accelerated by
GIRK antagonists. In a canine study, Hashimoto et al.95 showed that tertiapin-Q, a specific GIRK channel antagonist, prolongs atrial ERP and terminates AF induced by vagal stimulation, without affecting ventricular repolarization. Cha et al.66 showed that a GIRK channel antagonist is effective in an atrial tachyrdia-induced AF model.

[www.ncbi.nlm.nih.gov]
95. Hashimoto N, Yamashita T, Tsuruzoe N. Tertiapin, a selective
IK(ACh) blocker, terminates atrial fibrillation with selective
atrial effective refractory period prolongation. Pharmacol Res.
Apr 1 2006.

Tertiapin, a selective IKACh blocker, terminates atrial fibrillation with selective atrial effective refractory period prolongation.

Hashimoto N, Yamashita T, Tsuruzoe N.

Biological Research Laboratories, Nissan Chemical Industries, Ltd., 1470 Shiraoka, Minamisaitama, Saitama 349-0294, Japan. hashimotot@nissanchem.co.jp
Abstract

It is well known that vagal nerve tone plays a crucial role in atrial fibrillation (AF). Acetylcholine-activated potassium current (IKACh) mediates much of the cardiac response to vagal nerve stimulation (VNS), but the contribution of IKACh to AF remains unknown. We investigated the role of the IKACh channel in canine AF models using tertiapin, a selective IKACh blocker. Tertiapin (4-41 nmol kg(-1), i.v.) terminated AF in the canine VNS-induced and aconitine-induced AF models. The muscarinic M-receptor antagonist AF-DX-116 terminated AF in these models, but the adenosine receptor antagonist DPCPX had no effect. Thus it is likely that IKACh activation via the M-receptor has a crucial role in both models. Tertiapin (12 nmol kg(-1), i.v.) preferentially prolonged the atrial effective refractory period (ERP) but not the ventricular ERP under the VNS condition. This peptide (4-41 nmol kg(-1), i.v.) did not affect PQ, QRS and corrected QT intervals in isoflurane-anaesthetised dogs. These results suggest that a selective IKACh blocker is effective in canine AF models without affecting ventricular repolarisation, and might be useful for the treatment of patients with AF.

Tertiapin source:
[www.ascentscientific.com]

Interesting...

Mike and George:

From the University of Washington School of Medicine

Acetylcholine as a Neurotransmitter [courses.washington.edu]

About ¾ down (ACh=acetylcholine):

“In the second tracing, atrial cells display decreased action potential duration because there is no 'delay' for increasing K permeability of the membrane when the membrane becomes depolarized (K permeability is already increased by ACh action). The effect on action potential duration shortens the atrial refractory period. This is critical in patients who may have atrial flutter or fibrillation.”

Erling,

In the same article, "Note that all of these seemingly diverse effects of ACh are mediated by an increase in membrane permeability to K."

This got me to thinking about acetylcholine, hypokalemia and AERP (Atrial effective refractory period). Haven't answered this question yet. However our friend PC has thought about this, at least in relationship to hypomagnesmia (of course). This article is in our CR archives, [www.afibbers.org].
PC states, "Mg is required for activity by the cholinesterase enzymes(13). One of these, acetyl cholinesterase degrades acetylcholine, the neurotransmitter substance for the PNS and for the first part of the sympathetic nervous system (SNS), specifically the nicotinic receptors of the SNS. In fact, deficiency of magnesium and excess calcium both increase the release of acetylcholine. Deficiency of either magnesium or calcium prolongs the effect of acetylcholine(58). Mg deficiency translates to enhanced vagal tone further augmented by too much or too little Ca."

This may explain why my electrolyte program saves me from ACh vagal issues.

By the way, Mike, thanks for asking the question. As I go along, I keep learning & this was a significant breakthrough for me.

George

[www.ncbi.nlm.nih.gov]

Potentiation by hypokalemia of the effects of acetylcholine on the canine heart in situ.

Bertrix L, Bouzouita K, Lang J, Lakhal M, Chah QT, Faucon G.
Abstract

In the heart in situ of vagotomized dogs, atrioventricular conduction was studied by the His bundle potential recording, sinus rate continuously registered and the effective refractory period (ERP) of the atrial muscle measured by the extrastimulus method. The modifications induced by the acute lowering of plasma potassium concentration from 3.5 to 2.0 mmol/l obtained by hemodialysis appeared to be similar to those due to parasympathetic stimulation and the effects of hypokalemia and acetylcholine (ACh) on the atrioventricular (A-V) and sinoatrial nodes as well as on the atrial contractile tissue gave rise to potentiation. Intraaortically injected near coronary ostia in a dose lower than liminal dose, ACh enhanced to a large extent all the phenomena elicited by hypokalemia, since the variations respectively observed under the influence of hypokalemia alone and the combination of hypokalemia and ACh were as follows: lengthening of conduction time in the A-V node by 100 and 180%, reduction of sinus rate by 10 and 20%, shortening of the atrial ERP by 20 and 40%.


[www.springerlink.com]
"As all these alterations are similar to those due to acetylcholine (ACh) (Varghese et al. 1973; Giles and Noble 1976), the consequences of hypokalemia were presumably more pronounced in the presence of the vagal tone, all the more so as moderate degree of hyperkalemia has been conversely proved to counteract cholinergic effects on the heart, abolishing for instance an ACh-induced A-V block (Fish et al. 1963; Lievre et al. 1980)."

So, if you keep the Mg and K up, you don't need to take the PB or another anticholinergic med.

George and Erling,

Interesting stuff and many thanks for posting!

When I had my Exatest in Jan of this year, my Ca/Mg ration was TWICE over range (Mg 30 and Ca 7.0) and, as such, might well explain my ectopy/arrhythmia issues. What a shame I don't feel confident enough in Exa to get another test done now I've had two courses of IM Mg injections (each course 4mmol twice a week for 5 weeks) AND have supplemented more aggressively with Mg, K and Tau etc. My ectopy remains much the same but just one episode of AF in June (after stupidly binge drinking) terminated in an hour with 200mg Flec.

The bee-venom-derived Tertiapin Q looks very interesting: have any human trials for AF been done with it yet? If not, why not... is the drug quite dangerous in terms of side effects?

Interesting that low K is so similar to parasympathetic stimulation, and, as such, an especially bad thing for vagal AFrs. That said and in my own experiment of one, my own serum K has always been bang-on middle of range, and my Exa IC K was also bang-on middle of range. Nothing to say that keeping the K towards the higher end wouldn't help me nonetheless though...... although THAT said my issue is with low IC mg and the Mg has to be in fairly good shape before one can ramp up the Mg!

Great discussion guys and thanks again.

Cheers,

Mike

Hi Mike,

Haven't seen anything on the Tertiapin & humans.

I posted a while back on a Doctor from Wales suggesting magnesium ingestion with a nebuliser. It is supposed to be as effective as injections. Thought it might interest you. The link is below.

My unsupported opinion is that dietary choline is unlikely to increase ACh.

<[www.afibbers.org];
[drmyhill.co.uk]
<[www.afibbers.org];

[www.google.com]

All of the above convinces me that the Mg/K/taurine is a better way to go than PB, if the supplements can be made to work. My correspondent who has been on a one year trial of PB states it continues it efficacy. The one side effect is mild light sensitivity. He has also adjusted the dose upward slightly over time. I doubt if he would be receptive to the concept, but wonder in light of the above if supplemental Mg & K might enable him to lower his dose.

I'm guessing that PB may work in situation where the supplements do not. For vagal afibbers, I would insert PB before continued flecainide use in the 12 step program. Used in this way, I'd then retry supplements along with the PB & see if the dosage could be reduced. Even though PB does have side effects, it may be a better long-term bet than flecainide, which has its own issues with side effects & long-term efficacy.

Musings for the day.

Cheers,

George

Hi George,

As I've said previously, I do have a packet of PB ready for a trial, but I don't potentially want to rock the boat by trying it at this time of year (fall) when AF has historically struck most of the time for me. I concur with what you say about trying PB before Flec, but for me that's a bit reminiscent of something to do with a stable door and a bolting horse since I've been on 75mg BID Flec for over 2.5 years now. I tend to ramp down in spring to 50mg am and 75mg pm and I might well introduce a small dose of PB to try and get the Flec down to 50mg BID or even 25mg am and 50mg pm. I still have the Flec to fall back on as a PiP whatever - has always worked like a charm within an hour for me.

Thanks for the posts George,

Mike

Hi Mike,

Yes, PIP flec is a wonderful thing. My PB correspondent uses it too. He's recently gone back to modest alcohol consumption, which used to be a certain trigger for him. When questioned - he was unconcerned as PIP flec works well to convert him if the alcohol pushes him past the PB "barrier" to vagal afib.

In my case, it has been a great cofactor with my supplement program. In the last six years it has always worked in an hour or less (8 times) and before that it took 20 hours - (two times). The first converting my 2.5 month episode (which statistically it shouldn't even have done & then the next episode a month later and a month into my supplement program). I'm guessing my atria were stilled "stunned" after the 2.5 month episode.

It is one of the first things I learned about when I started frequenting this forum. A very useful tool indeed!!!!

Cheers,

George

George/ Mike,

I am very interested in this discussion; as you probably remember PB worked well for me, except for the temporary vision impairment.

Lately I have been experimenting with yet another supplement, lecithin, based on a post a while back. Specifically I have been taking GNC Triple Lecithin 1200, which is High Choline Soy Lecithin supplying 420mg Phosphatidyl Choline; taking it twice daily, morning and evening.

Initially there was no (detectable) change in my afib frequency, however after a couple of weeks I began to notice "hard" beats in NSR, especially at night. Then, 3 weeks after I started the regimine I had 3 afib episodes, every other day, for 6 days (worst stretch I have had since my ablation). I stopped the lecithin and both the hard beats and the afib have abated.

So it appears that Choline may be a significant key for me.

I just wish I could find another anticholinergic that doesn't cause the vision problem; my GP and my pharmacist had no suggestions on that.

Would appreciate any comments or suggestions regarding what to try next.

Thanks,

EB

EB,

Thanks for this seeming verification of what I had imagined a possibility for some, that a high dietary intake of choline might possibly raise acetylcholine to the point of a cascade of effects eventuating in shortening of the AERP and dysrhythmia. Besides lowering dietary choline, as you have done, the corrective would be the logical tried and true: maximize cell membrane integrity to maximize functionality while minimizing K leakage, maximize intracellular K while minimizing intracellular Na, resulting in stretching out the refractory period to a point where sufficient coordination between atrial muscle cells is established. All other nutrients and strategies playing into this should be optimized, especially the Awsome Foursome of cardiologist Stephen Sinatra - magnesium, carnitine, CoQ10, taurine - required for cellular energy production and utilization (MgATP). See Jackie's 'The Strategy' [www.afibbers.org].

George's bottom line in a post above: "So, if you keep the Mg and K up, you don't need to take the PB or another anticholinergic med."

Be well!

Erling

E. B.

Has your vision impairment receded and vision back to normal?

It is one thing to have reversible side effects, permanent ones are another thing entirely.

George

George,

I visited my opthamologist 2 weeks ago and my far vision is actually slightly improved. My near vision is slightly worse; the doc said both changes are normal for a 54 year old and he doubts that my prescription changes were a result of taking PB.

He commented that he had seen a number of cases where various anticholinergics caused vision impairment; he said people with glaucoma should totally avoid those drugs. The cases he had seen were always reversable.

So it sounds like good news for some folks; I know that if I didn't have the vision sensitivity issue I would be taking PB right now.

EB

EB,

From what I understand from my one correspondent who has been taking PB for a year, the effective dose is just below the dose with side effects. Also this is very individual.

As I recall, you were on a 3mg/day dose.

One possible option would be to go to a compounding pharmacy and get PB compounded, perhaps in a liquid, where your dose increment could be very small. Then start very low, say 0.5 mg/day and work up till you experience a side effect, then back off & see if you still get the afib benefit. If the side effects are reversible, then experimentation wouldn't seem to be too risky.

There were two other anticholinergics mentioned by Dr. Reiffel, belladonna and urecholine.

George

Also paying attention to Jackie's post here: [www.afibbers.org] regarding your GERD

My GERD problem is pretty much solved by my low carb diet. I am in a maintenance mode right, eating minimal carbs and don't have any GERD symptoms. If I went back to the potatoes and rice, I don't doubt that my GERD would be right back with me.

Looking back with 20/20 hingsight, part of my GERD problem was caused when I went gluten free for about 6 weeks. The gluten free foods I was eating were generally highly glycemic, and this made my GERD worse (which made my afib worse).

But you don't know until you experiment on yourself-

Thanks