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        New Message Board Archives >> Medications, Treatments, Therapies 2003 >> Autonomic Imbalance, N-3 Fats, Choline
        
(Message started by: floridian on Oct 5th, 2003, 2:03pm)
Title: Autonomic Imbalance, N-3 Fats, Choline
Post by floridian on Oct 5th, 2003, 2:03pm
The article below is about autonomic heart disease, but there are remarkable parallels to cluster headaches.  Clusterheads also have low HRV (heart rate variability), a measure that predicts arrythmia and sudden death (low is bad). Clusterheads are also more susceptible to heat and cold stress.  Cluster heads also have low choline - choline improves sympathetic/parasympathetic activity, which is out of whack in CH.  Cluster heads have increased Tumor Necrosis Factor (TNF) and Interleukin-6 (IL-6).  N-3 fats (flax oil and fish oil) and CoQ10 reduce TNF and IL-6.  N-3 fats, Choline and CoQ10 restore some circadian rythms.  

Standard disclaimer: it ain't proven yet. These parallels might be entirely coincidental.  On the other hand, flax oil is an inexpensive nutrient with lots of benefits and is low risk.  CoQ10 isn't exactly cheap, but it is safe and useful in many conditions.  Supplementation with these nutrients takes time (a few weeks) for the effects to show up.



Quote:
Biomed Pharmacother. 2002;56 Suppl 2:257s-265s.       Related Articles,  Brain-heart connection and the risk of heart attack.  Singh RB, Kartik C, Otsuka K, Pella D, Pella J.

   Autonomic functions, such as increased sympathetic and parasympathetic activity and the brain's suprachiasmatic nucleus, higher nervous centres, depression, hostility and aggression appear to be important determinants of heart rate variability (HRV), which is, itself, an important risk factor of myocardial infarction, arrhythmias, sudden death, heart failure and atherosclerosis. The circadian rhythm of these complications with an increased occurrence in the second quarter of the day may be due to autonomic dysfunction as well as to the presence of excitatory brain and heart tissues. While increased sympathetic activity is associated with increased levels of cortisol, catecholamines, serotonin, renin, aldosterone, angiotensin and free radicals; increased parasympathetic activity may be associated with greater levels of acetylecholine, dopamine, nitric oxide, endorphins, coenzyme Q10, antioxidants and other protective factors. Recent studies indicate that hyperglycemia, diabetes, hyperlipidemia, ambient pollution, insulin resistance and mental stress can increase the risk of low HRV. These risk factors, which are known to favour cardiovascular disease, seem to act by decreasing HRV. There is evidence that regular fasting may modulate HRV and other risk factors of heart attack. While exercise is known to decrease HRV, exercise training may not have any adverse effect on HRV. In a recent study among 202 patients with acute myocardial infarction (AMI), the incidence of onset of chest pain was highest in the second quarter of the day (41.0%), mainly between 4.0-8.0 AM, followed by the fourth quarter, usually after large meals (28.2%). Emotion was the second most common trigger (43.5%). Cold weather was a predisposing factor in 29.2% and hot temperature (> 40 degrees celsius) was common in 24.7% of the patients. Dietary n-3 fatty acids and coenzyme Q10 have been found to prevent the increased circadian occurrence of cardiac events in our randomized controlled trials, possibly by increasing HRV. We have also found that n-3 fatty acids plus CoQ can decrease TNF-alpha and IL-6 in AMI which are pro-inflammatory agents. There is evidence that dietary n-3 fatty acids canenhance hippocampal acetylecholine levels, which may be protective. Similarly, the stimulation of the vagus nerve may inhibit TNF synthesis in the liver and acetylecholine, the principal vagal neurotransmitter, significantly attenuates the release of pro-inflammatory cytokines TNF-alpha, interleukin 1,6 and 18, but not the anti-inflammatory cytokine IL-10 in experiments. Therefore, any agent which can enhance brain acetylecholine levels, may be used as a therapeutic agent in protecting the suprachiasmatic nucleus, higher nervous centres, vagal activity and sympathetic nerve activity which are known to regulate the body clock and HRV and the risk of SCD and heart attack.
Title: Re: Autonomic Imbalance, N-3 Fats, Choline
Post by ave on Oct 5th, 2003, 2:56pm
Floridian, far be it from me to doubt you, but where did all this wisdom about the physical make-up of clusterheads come from?

Is there somewhere a general overview of our choline levels and interleukin-6 and TNF and HRV etc.? Please direct me to it.
Or have you combined the results of different research programs? I am not asking for a lit list, just want to know how your data were gathered.

What I now wonder about is, if there's so little known about clusters and sufferers - see the medical encounters reporterd on wthis website - how can there be so much known about it wit? Or was the sample small(ish) and maybe not representational?

Just wondering a lot...
Title: Re: Autonomic Imbalance, N-3 Fats, Choline
Post by Pinkfloyd on Oct 5th, 2003, 11:44pm

on 10/05/03 at 14:03:37, floridian wrote:
 CoQ10 isn't exactly cheap, but it is safe and useful in many conditions.  Supplementation with these nutrients takes time (a few weeks) for the effects to show up.


CoQ10 has been showing some rather remarkable numbers (positive) in migraine treatment. I'm sure that there is some work being done in this area with regards to clusters.
Fish oil has long been thought to have a positive effect on clusters.
Good work Floridian!
Title: Re: Autonomic Imbalance, N-3 Fats, Choline
Post by Pinkfloyd on Oct 5th, 2003, 11:50pm

on 10/05/03 at 14:56:17, ave wrote:
What I now wonder about is, if there's so little known about clusters and sufferers - see the medical encounters reporterd on wthis website - how can there be so much known about it wit? Or was the sample small(ish) and maybe not representational?

Just wondering a lot...


Not to speak for Floridian, but the people here aren't seen by the people doing all the research being done on clusters. There is a great deal known about the make up of cluster sufferers. Far beyond whether or not there are more hazel eyes than blue eyes among them.

PF
Title: Re: Autonomic Imbalance, N-3 Fats, Choline
Post by ave on Oct 6th, 2003, 1:59am
Pink, I was not attacking anybody, just wanted to know where - and why we don't know this research is there...

Not knowing I may get heart attacks sooner than anything else... that sort of thing too.

So I am still wondering where.
Title: Re: Autonomic Imbalance, N-3 Fats, Choline
Post by Pinkfloyd on Oct 6th, 2003, 7:57am

on 10/06/03 at 01:59:18, ave wrote:
Pink, I was not attacking anybody, just wanted to know where - and why we don't know this research is there...


I know you weren't attacking anyone Ave.

As to why most people here don't know of the research, I have my theories and it's not because the research isn't being done.

PF
Title: Re: Autonomic Imbalance, N-3 Fats, Choline
Post by floridian on Oct 7th, 2003, 8:19am
Most of my search/research is done with Pubmed.  For those of you not familiar with it, it is a free, online database from the US National Institutes of Health that indexes over 12 million articles   (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi).

A Pubmed search on "cluster headaches" returns 1615 articles.   Some of these just mention clusters in one sentence (listing all the types of headaches), or are very general articles describing what a cluster headache is.  Some of the articles (especially the older ones) do not include  an abstract or synopsis.  But there are probably a thousand or so abstracts of articles that deal with the causes and treatments of clusters.  A few of these articles try to summarize what is known, but most try to deal with one or two aspects of the disease.

I think there is a fair amount of factual information, but still not a clear understanding of the disease.  If factor X is elevated in clusters, is that a cause, or just a side effect?  In many areas, there are only a few articles, which may not always show the same results.  It's complex stuff, and there is less research for clusters than for 'popular' diseases like migraine.   What I try to do is take something that is known about clusters, and relate it to other research - looking for chains of cause and effect.  There was an article I read in the late 80s about public secrets in the medical literature.  In the article's example, there was little in the way of treatments for meniere's disease.  The author started with what was known about the disease, researched those factors, and worked out, out, and then back to the start to generate hypotheses about possible treatments.  That's what I often do.

Question everything. Everyone can make mistakes.  I'm not too worried about what people say - reality is the harshest critic. The community of cluster heads needs to ask critical questions to make progress and get things right.  
Title: Risk Factor
Post by floridian on Oct 7th, 2003, 9:47am
The idea that cluster headache sufferers have low HRV (which is a risk factor for heart problems) is something of a break with the conventional idea that "clusters won't kill you, even though it may feel like it."  But having a risk factor is not the same as a death sentence - high cholesterol, high blood pressure, or any other similar condition should trigger concern and action, but it needs to be put into perspective.  Right now, it's not really clear what that perspective should be.  

Some general thoughts:

Abortives are not enough.  They ease debilitating pain, but they do not treat the underlying disorder.

The headache is not the disease - cluster headaches are the fruit of a tree that goes much deeper than that painful little spot behind the eye.

The underlying disorder in cluster headaches is more than a nuisance. It disturbs the body in many ways, and over the long run, these stresses can cause other problems.

Title: Choline, Acetylcholine, Nicotine
Post by floridian on Oct 7th, 2003, 10:09am
Alot of research has focused on serotonin, and that has been useful.  The triptans can abort a cluster, and methylsergide is a prophylactic.  But other neurotransmitters deserve more attention, particularly acetlycholine.

Acetylcholine is made in the body from choline. Choline levels are low in clusterheads.  Nicotine is an acetlycholine agonist - it fits in the acetylcholine receptor and triggers those nerves to fire.  The fact that an unusually large percent of people with clusters smoke or did smoke raises some interesting questions.  Is there an underlying problem with acetylcholine in clusterheads?  This might make clusterheads more susceptible to nicotine addiction;  tobacco could serve as a form of self-medication (with high side effects).  Alternatively, nicotine itself might mess up this neurotransmitter system and contribute to clusters.
Title: Re: Autonomic Imbalance, N-3 Fats, Choline
Post by andy on Oct 7th, 2003, 10:14am
Floridian, Thats very interesting, Im hooked bigtime, Keep up the good work   .............andy
Title: Re: Autonomic Imbalance, N-3 Fats, Choline
Post by eyes_afire on Oct 7th, 2003, 5:46pm
I have been very interested in acetylcholine for a while.  Ever since someone appeared on the message board touting Arricept as a possible treatment for CH... that was a while ago.

Anyway, here are a couple of links for the stout of heart.  They have been in my favorites for a long time, just sitting there.  Very technical stuff:

http://www.neurosci.pharm.utoledo.edu/MBC3320/acetylcholine.htm

http://www.neuro.wustl.edu/neuromuscular/mother/acetylcholine.htm

I have no clue if the info is of any practical use, but it will probably tell you all you ever wanted to know about acetylcholine.

FWIW

--- Steve
Title: Re: Autonomic Imbalance, N-3 Fats, Choline
Post by ave on Oct 8th, 2003, 4:31am
Okay, thanks for all the references. I'll study them quietly, though chemistry was never my big thing.

I AM curious however about the innuendo, jiminmil. Is there somebody/something/some hidden power, that keeps us from taking note of this?
Title: Re: Autonomic Imbalance, N-3 Fats, Choline
Post by ozzman on Oct 8th, 2003, 12:10pm
Found a couple of references on the autonomic system imbalance, mainly by Italian researchers, but I think this one is interesting:


Quote:
Br Med J (Clin Res Ed). 1984 Jan 28;288(6413):268-70.  Related Articles, Links  


Erythrocyte choline concentrations and cluster headache.

de Belleroche J, Cook GE, Das I, Joseph R, Tresidder I, Rouse S, Petty R, Clifford Rose FC.

Erythrocyte choline concentrations were measured in patients with cluster headache and age related control subjects. Concentrations were significantly reduced in the patients with headache both during a cluster period and between clusters, being 58% and 55% of the control value, respectively. After two weeks' treatment with lithium, choline concentrations in the patients with cluster headache increased to 78 times the control value (mean 369.2 mumol/l (3840 micrograms/100 ml) compared with 4.7 mumol/l (49 micrograms/100 ml]. The presence of depressed erythrocyte choline concentrations during and between cluster attacks indicates that this may be a predisposing condition which results in a cluster attack only when associated with a trigger factor.



Ozzy
Title: Re: Autonomic Imbalance, N-3 Fats, Choline
Post by floridian on Oct 8th, 2003, 1:01pm
I saw the article on lithium/choline a while back, and posted under a different thread.  This seemed like a promising research line in the early to mid 80s, then nothing ....  

I'm not in cycle now, but have anxiety and palpitations.  Started on Saint Johns Wort two weeks ago, and choline supplements a few days ago.  I'm taking 300-some milligrams choline per day (1 1/2 tablets, 1/2 tablet at each meal). I may ramp up to 1 tablet per meal if I can tolerate the choline and don't see results at the lower dose.  Also taking flax oil (regularly now, instead of 2-3 times per week) and added CoQ10 at 50 mg per day.

I also came across an article on HRV and exercise. In people recovering from heart attacks,  the HRV was improved by 2 ten minute aerobic exercise periods per day (at intensity of 80% of maximal advised heart rate). I think I will go for brisk walks instead of running. I would rather start off gradually than push too hard too fast.  Glad the weather is cooling off here.

Thanks for the acetylcholine links, eyes_afire.  I am digesting the first paper, which is very readable.
Title: Re: Autonomic Imbalance, N-3 Fats, Choline
Post by ave on Oct 9th, 2003, 4:14am
Floridian, you don't mention your age, but if you are anywhere over fifty, (brisk) walking is much, much beter than running.
Running may may cause damage to your joints but in walking you do give your bones enough pressure and excercise to prevent osteoporosis in a large part.

Just thought I'd mention it.
Title: Re: Autonomic Imbalance, N-3 Fats, Choline
Post by floridian on Oct 9th, 2003, 7:30am
Ave,

I am closer to 40 than 50, but agree with you that jogging is jarring, and can damage the cartilage.  Moderation and gradual progress is better than starting strong and dropping out due to over-exertion.  
Title: Re: Autonomic Imbalance, N-3 Fats, Choline
Post by ozzman on Oct 17th, 2003, 1:44pm
Here is a stab in the dark, I just read about this newly approved drug (by the FDA) in the US for the treatment of later stages of Alzheimer's disease, according to the article, the drug works by blocking excess glutamate. Glutamate receptors are involved in CH. Do a search in pubmed on glutamate and CH and you will find a few articles. There is nothing on the drug MEMANTINE for CH. For general info on memantine, look here:

http://www.memantine.com/inhalte/s1.html

Who knows, there may be more stuff that we can add to the arsenal...

Ozzy
Title: Re: Autonomic Imbalance, N-3 Fats, Choline
Post by floridian on Oct 17th, 2003, 2:51pm
Theanine (an amino acid found in tea) blocks NMDA/glutamate nerve signals.  A cup of tea has 25-65 mg of theanine.  Theanine also increases GABA in the brain.  The catechins in tea inhibit TNF and other inflammitory cytokines, and reduce nitric oxide production.  


Quote:
Biol Pharm Bull. 2002 Dec;25(12):1513-8.    Neuroprotective effects of the green tea components theanine and catechins.  Kakuda T.  Central Research Institute, Itoen, Ltd, Shuzuoka, Japan.

   The neuroprotective effects of theanine and catechins contained in green tea are discussed. Although the death of cultured rat cortical neurons was induced by the application of glutamic acid, this neuronal death was suppressed with exposure to theanine. The death of hippocampal CA1 pyramidal neurons caused by transient forebrain ischemia in the gerbil was inhibited with the ventricular preadministration of theanine. The neuronal death of the hippocampal CA3 region by kainate was also prevented by the administration of theanine. Theanine has a higher binding capacity for the AMPA/kainate receptors than for NMDA receptors, although the binding capacity in all cases is markedly less than that of glutamic acid. The results of the present study suggest that the mechanism of the neuroprotective effect of theanine is related not only to the glutamate receptor but also to other mechanisms such as the glutamate transporter, although further studies are needed. One of the onset mechanisms for arteriosclerosis, a major factor in ischemic cerebrovascular disease, is probably the oxidative alteration of low-density lipoprotein (LDL) by active oxygen species. The oxidative alterations of LDL were shown to be prevented by tea catechins. Scavenging of *O(2)(-) was also exhibited by tea catechins. The neuroprotective effects of theanine and catechins contained in green tea are a focus of considerable attention, and further studies are warranted.
Title: Zinc a very potent glutamate-NMDA inhibitor
Post by floridian on Oct 17th, 2003, 3:10pm
Zinc.  Inexpensive.  Essential in low doses, toxic at higher doses.  A very potent inhibitor of the glutamate-NMDA receptor!!


Quote:
Pol J Pharmacol. 2002 Nov-Dec;54(6):681-5.
   Interaction of zinc with antidepressants in the forced swimming test in mice.    Szewczyk B, Branski P, Wieronska JM, Palucha A, Pilc A, Nowak G.   Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343, Krakow, Poland.

   Recent preclinical data have suggested that glutamate NMDA receptor may be involved in the mechanism of action of antidepressant treatments. Functional antagonists of the NMDA receptor complex exhibit an antidepressant-like effect in animal tests that predict antidepressant activity and in animal models of depression. Zinc, a very potent inhibitor of the NMDA receptor, is active in the forced swimming test in rats and mice. The present study investigated the interaction of zinc with antidepressants in the forced swimming test in mice. Mice were injected with imipramine or citalopram alone and in combination with zinc. Low, ineffective per se doses of imipramine and citalopram administered together with low, ineffective doses of zinc were active in this test. The present data support the notion that inhibition of the NMDA receptor participates in an antidepressant action, and further demonstrate particular role of zinc in this activity.
Title: Re: Autonomic Imbalance, N-3 Fats, Choline
Post by wadj on Oct 18th, 2003, 2:49pm
Hello to all of you beautiful people who have shared their knowledge and pain.  I have been a CH sufferer for fifteen years and have had a neck surgery in hopes to clear the problem.  It did correct the neck "on fire" and yet the headaches plague me.  I take 1800 mg of neurontin and it really has deminished the pain and helps me rest better throughout the night.  I feel that my life is always revolving around my headaches.  The quality of life surely has been squelched, but I have a wonderfully understanding husband.  All of our children are raised and we have seventeen grandchildren.  I have a part time job, but for now am mending a broken left arm, the humerus bone.  I did a body slam on the gym floor where I work.  Now I have another pain to add to the already exsisting pain.  I wish I could say I had a solution, but the doctor I see has made sure I have a supply of hydroconone, in case I have a cycle get out of hand.  I take the lowest dose of HMT, estravest for osteo and supplements, calcium, mag, ester C, selenium and vit. E, as I have very poor fingernails and dry skin.  The headaches are just downright debilitating and I appreciate all that you are informing me of.  I felt that I had done enough research and just had to go on living with it, learn to work through the pain.  It is soooo very hard.  Thanks you and keep the faith.  I pray for all of you to never give up.  DJ


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