Marnie
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posted
It appears Bb's toxin is an acid from the breakdown of tryptophan. It is quinolinic acid.
Now, in researching Alzheimer's, I found the Omega 9 called oleic acid in coconut oil can help reverse AD. It appears to increase PPARY (which is deficient in sarcoidosis) too.
Anyway, I simply took the molecular formulas of those 2 acids and this happened:
Neurotransmitter receptor antagonists work by keeping the level of the neurotransmitter higher, longer.
It is only when a neurotransmitter is able to lock on, transmits a message and then is broken down (to be remade) does it really do its job.
This is happening all the time at INCREDIBLE SPEEDS...neurotransmitter made, locks onto a receptor, message sent, neurotransmitter broken down.
Prozac works by keeping the level of serotonin higher, longer by interferring with the receptors.
Follow?
It is my understanding that acetylcholine is the ONLY neurotransmitter present in BOTH the body AND the brain...and I do believe Bb is messing with acetylcholine levels...bigtime.
In a lab, we might not be able to get those 2 acids to structurally combine in the exact way, but can our bodies do that?
Can we use oleic acid to combine with the breakdown product of tryptophan i.e., quinolinic acid and make that polycyclic diterpenoid alkaloid to keep our levels of acetylcholine higher, longer?
[ 08-20-2009, 02:03 AM: Message edited by: Marnie ]
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TerryK
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I found early on through muscle testing that things that helped increase my acetylcholine helped my symptoms, particularly air hunger but also brain fog/function.
In a nutshell: Action of Toxin The action of botulinum (as well as the toxin from the Lyme spirochete) is to prevent, through its action as a proteolytic enzyme, the release of the neurotransmitter acetylcholine.
Nerve endings may be associated with other nerves or muscles (the neuromuscular junction). To understand this mechanism in greater detail, consider the basic principles of nerve physiology described below...
More from the article:
Dietary Supplements in Lyme Disease One of the known actions of the Lyme spirochete toxin is to diminish the release and availability of the neurotransmitter acetylcholine, a simple organic compound (see above for chemical structure).
This substance is biosynthesized by the body as required in nerve activation and transmission. Supplementation by the precursors of acetylcholine synthesis would be of value to Lyme patients since they have a deficiency of this substance. (See Listing 1.)
Listing 1: Dietary Supplements Increasing Acetylcholine Synthesis Improving Neurologic Function
If the inhibition of acetylcholine release were total, Lyme patients and those suffering from food poisoning would not be able to move; they would be completely paralyzed.
Since the blockage is only partial, any increase in the amount of available neurotransmitter would benefit anyone experiencing neurotransmitter blockage. For this reason, dietary supplements increasing the amount of available acetylcholine have been shown to benefit Lyme patients.
......
Acetylcholine Formation In Chart 3, we can see phopsphatidylcholine is a constituent of lecithin, a well- known dietary supplement. Acetylcholine is simply choline to which an acetyl group (CH3CO-) has been attached.
Lecithin is the source of choline, and acetyl-L-carnitine (ALC) is the source of the acetyl group. Carnitine is synthesized by the body and requires several factors, including the amino acid lysine and vitamin C (ascorbic acid). The supplement known as SAM (S-adenosylmethionine) supplies methyl groups (CH3-) to lysine, forming trimethyllysine.
This compound is further processed, requiring additional vitamin C, resulting in carnitine that supplies the necessary acetyl group.8,9
My test results show deranged tryptophan and increased quinolinic acid.
I beleive this is partly why pain levels are so high. Supplementing with tryptophan helps pain greatly (or it did a few years ago) but potentially increases quin so not a good idea.
I've copied part of a thread that I posted (I think this is one of those threads that got deleted - not sure) --------------------------------------------------
In a nutshell, Quinolinic acid is a metabolite of tryptophan and it appears that in the presence of CNS inflammation, tryptophan may be converted to quinolinic acid.
My Notes: (mostly from Buhner's book I think) ROS (reactive oxygen species) are created to kill spirochetes - lyme spirochetes are potent stimulators of ROS.
When borrelia invades the brain and CNS, they create a potent stimulation of Quin.
The two together (Quin and ROS), act synergestically to damage the CNS.
Quin potentiates the effect of free radicals and other ROS on tissues, especially the brain.
Quin also induces the function of nuclear factor-kappa B (NF-kB). NFkB acts as a neurotoxin, exacerbating neuronal death.
Quin's effect on the brain is severe: neurotransmitter intereference damage to the synaptic connections brain atrophy cerebral volume loss neuronal death
major areas of impact are: hippocampus striatum limbic cortex amygdala
The main problems associated with these are impairment of memory related tasks, memory and recall deficits and confusion.
Without specific therapy to protect the brain from Quin and stimulate repair of damaged areas, the damage is unlikely to correct. Abx alone do nothing to protect or help regenerate damaged areas.
Selenium 200 mcg per day zinc picolinate with copper 20-30 mg zinc with copper Melatonin .6 to 3 mg daily take at night, just before bed because it can cause grogginess
I'll try to come back later and post more when I have time to go through my files for more info. You can search here for more too since I've posted a number of times about these issues.
I haven't heard of plycyclic diterpenoid alkaloid but I'll research that when I have a few minutes.
Fourteen patients with Borrelia burgdorferi infection were investigated for possible abnormalities of tryptophan and neopterin metabolism.
Four patients (2 were investigated before therapy, 2 when therapy had been already started) had acute Lyme neuroborreliosis, and 10 patients were investigated months to years after an acute infection.
Increased concentrations of neopterin and of the tryptophan-degradation product, L-kynurenine, were detected in the cerebrospinal fluid of patients with acute Lyme neuroborreliosis; one patient presented with subnormal tryptophan.
Similar but less marked changes were seen in the treated patients and in some of the patients with Lyme encephalopathy. No such abnormalities were seen in the serum of the patients.
The data indicate a role of the immune system and particularly of endogenously formed cytokines, like interferon-gamma and tumour necrosis factor-alpha, effecting tryptophan and neopterin metabolism in patients with acute Lyme neuroborreliosis.
PMID: 7865624 [PubMed - indexed for MEDLINE]
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Cindy Ss
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posted
Hi,
I am so interested in this due to the fact I am taking L-tryptophan to help with my anxiety. According to this research is it the wrong thing to do? Due to the increase in Quin could I be helping the Lyme and hurting my recovery?
This is confusiong to me due to I am so new to this only in treatment for 2 months now.
Sorry but I hope you can explain this in a newbie way:)
Is L-tryptophan the wrong supplement? If so which would be bette for anxiety? I am supposed to take the L-tryptophan along with L-tryosine to level things out in my brain...
I think it is all experimental though so any help from you would be so much appreciated.
Marnie
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posted
I think my sis' (highest level of Prozac) may have prevented "neuro" lyme.
Prozac helps keep the level of serotonin higher longer (preventing the breakdown of it). Serotonin is only broken down once it locks onto the receptors, transmits a message...is it then broken down...and ultimately remade...at ASTOUNDING speeds...all the time.
It did not, however, impact this disease from damaging the rest of her body.
Acetylcholine is needed for REM sleep as I understand it.
I know a lyme patient in Sarasota who was tested in a sleep lab and has NO REM sleep.
ONE of Bb's outer cell walls IS phosphatidylcholine.
"To characterize phospholipids in these organisms, spirochetes were metabolically labeled with [3H]palmitate or [3H]oleate;
B. burgdorferi contained only
phosphatidylglycerol and phosphatidylcholine (lecithin),
while T. pallidum contained phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and cardiolipin.
Relatively more arachidonic acid was incorporated into phosphatidylcholine (Lecithin) and phosphatidylinositol
when magnesium-deficient or EFA-deficient
animals were compared to the control group. PMID: 3152743
It is my understanding that AA (arachidonic acid) comes from the breakdown of the Omega 6s.
Terry K...I really appreciate the exchange of information!
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Cindy Ss
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posted
I'm sorry I don't mean to but in to this what seems to be very important information.
What does this all mean simply put, if you could please share...
Thank you, Cindy
I am under the impression that SSRI may protect our brains from harm? I have read this before...
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Marnie
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posted
We think oleic acid might help...a LOT.
It is an Omega 9 fatty acid. It is one of the things in coconut oil.
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TerryK
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When I took all my research into my N.D. regarding quin and tryptophan, she said that she thought tyrosine would take care of the problem so maybe that's what your doctor is thinking?
Later she told me that based on my research she took all of her patients off tryptophan but I don't know if she changed her mind later or not since I don't see her anymore.
I don't take taurine because I have a CBS upregulation (methylation cycle issue) and taurine is a sulfur based amino acid.
You may be fine with taurine. I haven't looked into how taurine balances tryptophan to keep quinolinic acid from being formed but hopefully your doctor understands it.
I'd bring this up with your doctor and ask for guidance. We aren't doctors here. Marnie has a medical background but I don't have formal training in medicine.
edited to add: For those with a sulfur problem. Sulfur increases ammonia. Borrelia increases ammonia. Increased ammonia = brain swelling and other deleterious effects. - Again, this is based on my research - I'm not a doctor and your doctor may not agree with this. Some doctors who are familiar with lyme do though.
Terry I'm not a doctor
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Marnie
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posted
If you missed this:
In sequence:
Metabolism of the Putative Neurotoxin Quinolinic Acid in Lyme Borreliosis (on the agenda of a lyme conference)
"C7H5NO4 An odorless, crystalline compound with a melting point of 190�C; soluble in water; ***inhibits glucose synthesis***. Also known as quinolinic acid."
A LONG time ago, I remember reading that Bb cannot grow in gelatin (gelatin has all of the amino acids except tryptophan). Indeed, Bb's genetic codes indicate it needs tryptophan (so do we).
Oddly, that double bonded O and single bonded OH is present on the "end" of Oleic acid...an Omega 9.
Marnie
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posted
I PERSONALLY would look at what AD patients are recommending re: dosages and timing of coconut oil.
Google these words:
Alzheimer's coconut oil
Yes...I think Prozac helped prevent NEURO lyme for my sis. She is on the highest doses allowed.
GABA can help with anxiety.
Depression and anxiety are two different "animals"...treated with different things.
This is all so incredibly complex...
To PREVENT lyme in DOGS...Frontline blocks the chloride channels.
GABA A and GABA C look to be chloride channels.
Once lyme IS present, however...
???
If we combine the use of Oleic acid (ultimately to make PPARY2) AND use abx. Will that COMBINATION work to destroy the infection?
I think the cure involves TWO things...taming down the immune response (getting the inflammatory cytokines DOWN) AND hitting Bb.
Terry K...I've wondered about nicotine PATCHES.
The acetylcholine receptors are called the nicotinic receptors...
NH3, Terry...looks like ACZ Zeolite binds it and it is eliminated via the urinary system.
I had an ear infection that didn't want to go away...finally the doc gave me an eardrop that contained a steroid AND an antibiotic. It worked.
I think we have to reduce the inflammation AND hit the pathogens...simultaneously.
Steroids are not good for lyme, but there ARE other things that reduce inflammation...esp. Mg.
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posted
Marnie, Do you think acetylcholine's ability to act as both an excitatory and an inhibitory neurotransmitter, depending on where it is used, could be what makes it susceptible to Bb?
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klutzo
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If I am interpreting this correctly, it is very upsetting.
I tried 5 times with 5 different docs to get help for my depression secondary to Lyme and got no help at all.
Anti-deps. put tons of weight on me and did not help the depression. Studies confirm they are no better than placebo for most people. Look it up yourself.
I am through with shrinks and am very ashamed of what my former profession has turned into since I left. They are nothing but legal drug pushers now.
L-tryptophan in very high doses at night has saved my life. I am so glad I found it. I don't think I could go on without the help it has given me. I take 1.5 grams at bed time and another 1.5 grams when I wake up around 3 am.
The other thing I need for mood is a very small dose of Pregnenolone. I take 5 mgs. 3 times weekly.
My short-term memory is awful, but I thought it was the low dose Xanax I take for muscle spasms that was causing that.
I've taken taurine in the past but not noticed any difference. I do take plenty of Mg and those other acetylcholine raising supps..
So, are you saying that I am choosing between suicidal depression or AZD? Some choice!
Also, if coconut oil is the answer, could we not take Caprylic acid and kill two birds with one stone, since it also kills candida and is made of coconut oil?
klutzo
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When I see these topics, I cannot help but wonder if Marnie has ever taken a college chemistry class. This makes little sense for many reasons. First off, you can't take the molecular formula and just randomly add it to another molecular formula to come up with something else that is meaningful.
That would be psuedochemistry based on molecular formulas that merely illustrate the relative ratios of each atom in a compound. It says little or nothing about the structure or number of atoms, or isomers. Many compounds share the same identical empirical formula, so knowing the empirical formula is relatively useless in the context in which this well-intentioned poster is attempting to use it here. Adding it together to get a new empirical formula, without any understanding of chemistry is also useless.
Marnie forgets the molecular formula: C7H5NO4 also represents dinicotinic acid, dipicolinic acid, lutidinic acid, 2-Nitrobenzoic acid, 3-nitrobenzoic acid, etc...
Before Marnie's supporters chide me for not asking questions because they think I don't understand and can't follow her logic, please understand that I have taken and passed college chemistry, physics, biology, microbiology and anatomy & physiology, as well as some basic pharmacology before I became ill. That background enables me to recognize when things don't add up.
So, when I point out flaws in these topics, it is not because I don't care about the patients in this forum. It is quite the opposite. I do care about the patients in this forum and that is why I sometimes feel compelled to point out the lack of logic and the mistaken conclusions it leads to. The reason I do not ask questions is because it would be a waste of time, her time and my time.
I think it is wonderful how caring and devoted Marnie is on her mission to help her sister until she misinterprets things in a way that can mislead patients here who desperate for real answers. Marnie is kind hearted and well intentioned. I admire the fact that she goes to such great lengths to try to understand this disease in order to help her sick sister. However, I don't want to see patients in this forum mislead or harmed by her erroneous conclusions.
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TerryK
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Lone - Marnie has a nursing degree. Do you have a degree in the medical field?
Terry
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I do not know the extent of Marnie's education, but as Terry pointed out, she does have a nursing degree.
Yes, some of this stuff seems to be a reach, logically speaking, but why not consider it if it turns out to work?
Although I've taken most of the college classes lonestartick lists--and aced them--I know my knowledge is woefully inadequate to think like a biochemist. I do, however, have an open mind and a willingness to learn.
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TerryK
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Marnie - Thanks for your efforts. The nicotine patch is an interesting thought and seems like a possibility.
I am running short on time right now as I need to get ready for a plane trip to my LLMD but I plan to study this further. I found the acetylcholine connection several years ago and don't plan to abandon it as a real issue that could yeild some treatment options. I think we are on the right track with this.
I don't believe I need a degree in chemistry to understand most of this but I can always ask my husband for help since he understands chemistry pretty well.
Terry
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Marnie
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Lonestartick...I made it CLEAR in the subject heading that my combining the molecular formulas is a "no-no".
I admitted I was doing a chemisty "no-no" in the subject heading.
But the results sure made me wonder!!!
To others...if we each have a set if identical building blocks - let's say 25 blue blocks,39 red blocks, 1 green block and 6 yellow blocks and we each use them to design a "structure" ...the stuctures will LOOK different and will FUNCTION differently.
But...the elements in the structure
are identical.
It is how they
are arranged
that determines if they "work" or not.
Repeating...I made it CLEAR in the topic, I did a chemistry "no-no" (!!!) by simply adding the various elements in both of the acids, but I found the results very curious.
It appears quinolinic acid is an agonist (helper) of the NMDA receptors (NMDA/glutamate) and MgSO4 is an antagonist.
To "counter" quinolinic acid, the body appears to upregulate melatonin to reduce oxidative neurotoxicity of quinolinic acid.
Do you need the links?
That makes sense...and WHY fatigue is a symptom of lyme (melatonin is needed for NREM sleep and is needed to
intitate sleep).
[ 08-22-2009, 12:25 AM: Message edited by: Marnie ]
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Marnie
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Klutzo...I don't think coconut oil (Oleic acid) ALONE is the answer.
It might be the combination...
of Oleic acid AND antibiotics.
Tame down the immune system (reducing inflammatory cytokines) AND... at the same time, hitting Bb with abx "help" (since Mg levels are too low).
Take a deep breath Klutzo and say this to yourself to counter your (understandable) anger at the medical community:
"Forgive them Father for they know not what they do."
Forgiveness is good and is necessary...I know, (personally) forgiveness is really hard!
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seekhelp
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posted
This is getting so wild. How about ONE continuing thread from Marnie started proposed ideas with each scientific study summarized in plain English with a point at the end of why it's being shown?
We see endless scattered posts and usually have to ask everytime, "Why is this posted - what does this mean?" We're not scientists here. For the most part, we're sick, intelligent people struggling with physical and neurological setbacks due to an illness. We may not be biochemical majors, but it doesn't mean we weren't good at what we do/did.
Scientists reside at Harvard, Mayo, Duke, Hopkins, and other academic institutions.
At times I feel like every one of these posts are made for the greater good of Lymekind. When one innocent sick person asks a specific question to Marnie, the next post instead of being focused on that person's direct question is another endless citation and two page study. Individuals deserve as much respect as scientists, especially new people here desperately seeking help.
Wanting to help people is commendable. I respect that. Rebutting people's comments, digging up endless threads to justify a post is not IMO. A nursing degree is respectable, but this work is PhD level and above most likely.
I have many super smart friends who took the same classes as Marnie and they wouldn't fathom undertaking this massive task or discovering the cure for Lyme disease w/o proper direction from the brilliant scientists of the world. I know many aren't willing to help, but someone?
Something has to change. We don't need to be blasting each other, but at the same time, guidelines are important. Sick people are down to their last dime and cannot spend money on uknowns anymore. Patient advocates should know this more than anyone. For goodness sake, it's not like we're the President of Vitacost or Iherb.
Let's all get along!
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Marnie
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Dinicotinic acid...same molecular FORMULA as oleic acid forms this complex:
dinicotinic acid-glutathione-chromium complex known as glucose tolerance factor = GTF.
For more information about GTF (to save you time), you can go to these websites:
[ 08-20-2009, 12:29 AM: Message edited by: Marnie ]
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glm1111
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I have a degree in nursing and have studied years of metaphysics and quantum physics and would never post any of those equations that could apply to disease. It would take me another lifetime to actually understand most of it myself anyway.
It would just cause much confusion and be very stressful to the people here looking for answere in laymans terms. I have yet to find any of the info Marnie posts to be of any use to the average person here suffering from this debilitaing disease.
The first paragraph at the beginning of this thread makes it sound like this is some kind of scientific discovery of self importance when it actually means nothing.
I have seen many people angered by your posts because of their confusing nature. Bringing a disagreement from another post to re hash it serves no purpose either.
Bringing clear and concise information that people could understand would be so much more productive towards helping people heal.
Gael
-------------------- PARASITES/WORMS ARE NOW RECOGNIZED AS THE NUMBER 1 CO-INFECTION IN LYME DISEASE BY ILADS* Posts: 6418 | From philadelphia pa | Registered: Jul 2008
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TerryK
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Seek - no one is required to read every post. That is the beauty of this forum. We can pick and choose what we find interesting and helpful.
While educational background is important it is not required to understand some of the more technical posts. Some people are capable of studying and understanding on their own.
I feel that the accusations that were leveled at Marnie are inaccurate and unfair. Put yourself in her position and read what was said in this post and several other posts and think about how you would feel. She has a right to defend herself.
Dawn in VA
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posted
"This is not a medical or scientific forum."
It is (or should be) an EVERYTHING forum. Period.
I feel everything relevant to Lyme and company should be welcome and up for discussion.
That said, however, due to the large volume of emotional responses that have risen here, maybe to cool things off the moderators would consider
adding a separate discussion board for the "scienficially-medically advanced" folks here like Marnie, Terry, etc. Those who want to check in there can, and those who don't won't.
I'm not being sarcastic in any way- I think this might be a good idea.
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Dawn in VA
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TO LIFE, regarding your comments....
Just what I said-- that perhaps the moderators would consider a separate discussion forum for these kinds of posts. They seem to get folks in an upheaval- too much heat.
[ 08-23-2009, 01:52 AM: Message edited by: Dawn in VA ]
-------------------- (The ole disclaimer: I'm not a doctor.) Posts: 1349 | From VA | Registered: Jul 2006
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posted
I see the same pattern every time - Marnie is trying to figure out the biochemistry of what's going on - lots of creative thinking going on based on some facts and some guessing, raising ideas, food for thought.
Then people come on saying they don't understand the scientific complexity, or they don't think it holds up scientifically.
My thoughts: Marnie, if at the end of your biochemistry discussion, to put a conclusion in simple terms so that those of us who have not studied biochem or cannot follow your discussion can understand what you're getting at.
For those who disagree with the science - I do see this as creative thinking, thinking outloud. Trying to figure it out. Interesting thinking.
Sometimes I go ahead and google and study what Marnie's referring to and learn more biochem.
Can we just accept it in that guise, read through it, think about it?
And evaluate the ideas without attacking each other?
Just my thoughts tonite.
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Marnie
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posted
I made a mistake in the original post...I reversed the molecular formulas for oleic acid and Quinolinic acid -
which I corrected above.
Way too much Quinolinic acid is being made. It is coming from macrophages.
My computer just froze...otherwise I would link that info.
Or...you could search for yourself..."Google"
macrophages quinolinic acid
TerryK and others who are interested...stay tuned re: oleic acid benefits.
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posted
Glad you're continuing to share this info with us and not backing down.
Thank you Marnie!
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TerryK
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Marnie - I haven't had a chance to look at all the links yet. Looks like some very good links. One talks about detoxx book. Piques my interest.
Haven't taken brewers yeast but I've been taking chromium picolinate and chromium GTF for over 5 years. Also take acetyl glutathione which so far seems to be the most effective oral glutathione for me. I've been on various forms of glutathione for many years but not the IV's.
I won't have time to really look at oleic acid but it looks like it has some relationship to renin and aldosterone but I haven't sorted through it yet. I am low renin and I *think* oleic acid might lower it even further. Would not be good for me. But again, I don't have a good understanding of oleic acid yet and why it might help.
Also, oleic acid looks like it might be hypotensive. This would not be good for those of us with dysautonomia because we are already hypotensive. The hypotensive effect may tie into renin and aldosterone. Wish I had more time but I don't right now.
Acai is high in oleic acid. I don't know much about it other than I get a ton of junk mail trying to sell me some.
Will be interested to see what you find about oleic acid.
Will keep checking back in here as time permits and will do more research later. Terry
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TO LIFE
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Any intelligent fool can make things bigger and more complex... It takes a touch of genius - and a lot of courage to move in the opposite direction. Albert Einstein
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TerryK
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TO LIFE - I love it when people allow discussion even when they don't agree with the subject and/or with the way it is being discussed.
I love it when people appreciate others even though they are different than themselves.
Edited to add: TO LIFE - I see you edited your post after I posted. You previously said you love that quote - you don't love it anymore? Posts: 6286 | From Oregon | Registered: Jan 2006
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TerryK
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TO LIFE - So glad you are doing better and have hope. We *must* keep looking for answers so we can all have hope.
You asked if anyone knows what RSD is. I assume you are talking about Reflex Sympathetic Dystrophy? I've read of other people on this forum with a similar onset. You don't see this mentioned as a diagnosis much here though.
I see you are up late too. I'm having trouble sleeping lately. I'm going to try to go to sleep now though.
I hope you keep improving just as I hope everyone with lyme disease has the tools they need to get better.
Take care, Terry
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TO LIFE
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Dear Terry,
God is the grestest Physican.
I make sure I sleep about 10 hrs. every night.
Someone with any wisdom at all realize's they know nothing.
Drexel Univerisity only puts people on Ketamine with a RSD DX., Marnie has brought up Drexel, they have sent several people over to GERMANY for a Ketamine Coma no less.
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seekhelp
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posted
Does anyone realize I made a thoughtful comment just looking for feedback? I received none from the direct poster. I was not rude. TerryK did comment. A little compassion maybe for the common folk w/o pharmacology degrees perhaps?
The next direct quote is:
"Dinicotinic acid...same molecular FORMULA as oleic acid forms this complex:"
I'm not going to comment more as I get it. I do think all this info in one thread called 'Marnie's Thoughts about Lyme and Hypothetical Treatment Philosophies' seems very smart though for the sake of us all. It seems like individual questions are not much appreciated.
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TerryK
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Seek said: Does anyone realize I made a thoughtful comment just looking for feedback?
If you want feedback, it's best to address a specific person or persons with a specific question.
Seek said: How about ONE continuing thread from Marnie started proposed ideas with each scientific study summarized in plain English with a point at the end of why it's being shown?
In my opinion, this kind of restriction would discourage interesting information from being posted. I don't feel it would not be practical or desirable.
What applies to one person must apply to all. It would be impossible to enforce. It would make it very time consuming to post anything and one would have to totally understand every study they post before posting it.
Sometimes I post a study that I may not totally understand and I hope for feedback from someone who understands it better than I do. OR maybe I just want feedback or ideas or just to share the parts that I do understand.
Seek wrote: I do think all this info in one thread called 'Marnie's Thoughts about Lyme and Hypothetical Treatment Philosophies' seems very smart though for the sake of us all.
Why should anyone be forced to post differently than anyone else? We all have our own styles which some find useful and appealing and others do not.
We each have the option of reading something or not. Each individual needs to find a way to use this forum to help themselves and to help others in the best way they know how.
There are many different styles and not all will mesh but we all have to try to be accepting of others just like in the real world.
Seek wrote: It seems like individual questions are not much appreciated.
In this forum in general, if the answer is known it will usually be given. If someone makes a comment or a critsism that is not specifically addressed to one person, there may not be a response.
If someone directly asks me a question, I'll respond if I see it with an answer or an "I don't know". I think most people try to do the same.
I often don't get feedback on my posts. I just assume that either no one knew the answer or the post did not interest those who read it.
When someone posts something that they want to discuss, just like in the real world, it is considered inappropriate for others to take over the conversation and disucss something totally different. It's no different here.
I must admit that I'm guilty of it myself at times. Unfortunately, this post has been diverted away from it's original purpose and now hopefully it will be allowed to proceed to the intended discussion.
Terry
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TerryK
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OK, one last post on the subject, then hopefully moving on.
In my view, this forum is like a room full of people all standing around discussing various topics. Not every topic that is being discussed will interest every single person in the room. Not every person in the room will understand every discussion.
This is a forum with thousands of people. Think how boring it would be if discussions were only allowed if we were sure that every person could fully understand the discussion.
Not only would it be impossible to know what subjects could be discussed but it would take tremendous effort to discuss anything. Subjects would be limited and thus learning would be limited.
Terry
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TO LIFE
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Dear Terry,
Alot of people are very sick on this forum.
No one needs to be mislead at all.
Why haven't all you bright people reached out to RSD patients?
You could make better use of your time, and truly be an asset?
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TerryK
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TO LIFE - I'm very sick myself. I don't have all the answsers. I try to help others here at lymenet with information that I am learning for myself and my family and by giving any info that I have found has made a difference in my symptoms/health.
My brother, sisters, their children and my mother are all sick. My brother is literally dieing and fairly fast. I'm trying to figure out how to help them and myself while at the same time, giving back some to the lyme community. I only have so much time and energy. I would help more if I could.
Terry
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TerryK
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I find it confusing when someone posts, people respond to the post and then they come back days later and delete several of their posts.
This is in response to a post from TO LIFE that she subsequently deleted. She said that given that my time was limited, I beg you to stop enabling.
TL - WOW!! It's awfully hard to satisfy some people. I've done my best respond to you and others in a kind and reasonable way. I don't consider that enabling.
Not sure if you've seen this Marnie -
1: Neurology. 1992 Jan;42(1):43-50. Links
Neuroactive kynurenines in Lyme borreliosis.
Halperin JJ, Heyes MP.
Department of Neurology, SUNY, Stony Brook.
Although neurologic dysfunction occurs frequently in patients with Lyme borreliosis, it is rarely possible to demonstrate the causative organism within the neuraxis.
This discordance could arise if neurologic symptoms were actually due to soluble neuromodulators produced in response to infection.
Since immune stimulation is associated with the production of quinolinic acid (QUIN), an excitotoxin and N-methyl-D-aspartate (NMDA) agonist, we measured levels of CSF and serum QUIN, and lymphokines.
Samples were obtained from 16 patients with CNS Borrelia burgdorferi infection, eight patients with Lyme encephalopathy (confusion without intra-CNS inflammation), and 45 controls.
CSF QUIN was substantially elevated in patients with CNS Lyme and correlated strongly with CSF leukocytosis. In patients with encephalopathy, serum QUIN was elevated with corresponding increments in CSF QUIN. Lymphokine concentrations were not consistently elevated.
We conclude that CSF QUIN is significantly elevated in B burgdorferi infection--dramatically in patients with CNS inflammation, less in encephalopathy.
The presence of this known agonist of NMDA synaptic function--a receptor involved in learning, memory, and synaptic plasticity--may contribute to the neurologic and cognitive deficits seen in many Lyme disease patients.
TerryK
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This is an older article but may be useful. I am looking for an article I found a few years ago that was written by a professor about tryptophan and aids. If I find it, I'll post it. It was very good.
A few random thoughts: Low carb intake, less uptake of tryptophan possibly less production of toxic metabolites like quin. Maybe this is partly why people with lyme and fibro type illnesses notice less brain fog with reduced carbs?
Didn't totally understand all the implications in the part where he talks about the synthesis of serotonin but if limited BH4 (Tetrahydrobiopterin) means limited serotonin (in my mind limited serotonin means more depression), this may be significant for some of us with methylation cycle issues and lyme infections.
The reason being - lyme increases ammonia - ammonia uses up BH4. Some methylation cycle defects further lower BH4. Low BH4 also means more severe parasitic infections (babesia too??).
http://www.ceri.com/fftrypto.htm This article originally appeared in the July 1992 issue of ForeFront--Health Investigations. Molecular diagrams are not yet installed.
Medical Forefronts Tryptophan Metabolism in Chronic Disease and AIDS by Steven Wm. Fowkes Tryptophan plays a unique role in defense against infection because of its relative scarcity compared to other amino acids.
During infection, the body induces tryptophan-catabolizing enzymes which increase tryptophan's scarcity in an attempt to starve the infecting organisms [Brown, et al., 1991].
In unresolved chronic infections, tryptophan metabolism remains disturbed. The biological disturbances caused by widespread tryptophan deficiency may be substantially responsible for some of the cognitive deficits, neuroendocrine dysregulation, and immune incompetence associated with AIDS, autoimmune disease, and other chronic disease states.
Tryptophan Catabolism Tryptophan is metabolized in several tissues by different enzyme systems. The primary site of tryptophan catabolism is the liver where tryptophan oxidase metabolizes tryptophan with molecular oxygen as the oxidizing agent. The oxygen is used to split the 5-member nitrogen-containing ring on the tryptophan molecule (see illustration page 4) generating kynurenine (KYN) derivatives.
A little over a decade ago, tryptophan oxidase was widely believed to be the only tryptophan-catabolizing enzyme. Then Japanese researchers discovered indoleamine-2,3-dioxygenase (IDO), also called indole oxidase. In peripheral tissues and in the brain, IDO is the only tryptophan-catabolizing enzyme, using superoxide anion as the oxidizing agent. IDO is a more general enzyme. It has a limited capacity to oxidize a broad class of compounds called indoles (see illustration), which are chemically related to tryptophan. IDO has less specificity for tryptophan than the hepatic tryptophan oxidase enzyme.
Small amounts of tryptophan (approximately 1%) are metabolized by brain tissue into serotonin (a neurotransmitter) and melatonin (a neurohormone). During infection, tryptophan deprivation reduces the activity of these pathways and may influence vital regulatory functions. In addition, tryptophan catabolism in the brain and peripheral tissues produces toxic chemicals which stimulate excitatory neurotransmitter pathways.
NMDA Receptors Modern neuroscientists have come to realize that glutamate (glutamic acid) and aspartate (aspartic acid) play a global role as excitatory neurotransmitters in the brain. The receptors for glutamate and aspartate regulate ion channels which control the flow of sodium, potassium, calcium, magnesium and chloride ions across nerve membranes. They are named NMDA receptors after their natural agonist N-methyl-D-aspartate, the stimulating chemical for which they have affinity.
Some chemicals have extremely high affinity for the NMDA receptor. They are called excitotoxins because of their ability to bind to the NMDA receptor and overstimulate the excitatory nervous system. Overstimulation of the central nervous system is believed to be involved in the development of numerous neurodegenerative conditions like Huntington's disease, cerebral ischemia and hypoxia, and temporal-lobe epilepsy. Such excitatory overstimulation may also be involved in Alzheimer's disease, Parkinson's disease, AIDS dementia, hypoglycemia, schizophrenia, and anxiety disorders [Schwarcz and Du, 1991]. Although glutamate and aspartate are excitatory neurotransmitters and may play a limited role in neurodegeneration, excitotoxins are dramatically more potent. The tryptophan metabolite quinolinic acid, for example, is one hundred times more potent than glutamate in rats.
Another tryptophan metabolite, kynurenic acid (KYNA), is a nonselective blocker of NMDA receptors. Interestingly, it also decreases nervous system susceptibility to excitotoxins, especially quinolinic acid. KYNA and quinolinic acid are both naturally present at concentrations several orders of magnitude lower than glutamate and aspartate. Quinolinic acid levels are similar across species, but KYNA varies substantially. Man has 50 times higher KYNA levels than rats. Although some researchers have suggested that deficiencies of KYNA may be associated with the development of neurodegenerative diseases, the specific roles that quinolinic and kynurenic acids play in chronic infection or degenerative disease remains to be elucidated.
Tryptophan Absorption and Metabolism
In most proteins, tryptophan is the least abundant essential amino acid, comprising approximately 1% of plant proteins and 1.5% of animal proteins. Although the minimum daily requirement for tryptophan is 160 mg for women and 250 mg for men, 500-700 mg are recommended to ensure high-quality protein intake. Actual tryptophan utilization is substantially higher. Men use approximately 3.5 grams of tryptophan to make one days's worth of protein [Peters, 1991]. The balance is obtained by hepatic recycling of tryptophan from used (catabolized) proteins.
Dietary tryptophan is well absorbed intestinally. About 10% of the tryptophan circulating in the bloodstream is free, and 90% is bound to the protein albumin. The tryptophan binding site on albumin also has afinity for free fatty acids (FFAs), so tryptophan is displaced when FFAs rise, as when fasting.
Tryptophan transport into the brain is regulated by an active transport enzyme system which also transports other large neutral amino acids (LNAAs) like phenylalanine, tyrosine, leucine, isoleucine, and valine. Paradoxically -- because of the competitive influence of LNAAs -- brain uptake of tryptophan is inhibited after consumption of tryptophan-rich (and LNAA-rich) high-protein foods.
Carbohydrates and insulin, on the other hand, lower LNAAs and enhance tryptophan transport into the brain.
Although tryptophan is not usually the limiting amino acid in protein synthesis, tryptophan may become insufficient for the normal functioning of other tryptophan-dependent pathways.
Numerous lines of research point to tryptophan's central role in regulation of feeding and other behaviors. Tryptophan is not only typically the least abundant amino acid in the liver's free amino acid pool, but liver tryptophan-tRNA levels fall faster during food deprivation than other indispensable amino acids [Rogers, 1976].
Under fasting conditions, and possibly in wasting syndromes, tryptophan may become the rate-limiting amino acid for protein synthesis [Peters, 1991].
The LNAA transport enzyme responsible for tryptophan transport across the blood-brain barrier also has high affinity for kynurenine and 3-hydroxykynurenine, the two early amino-acid metabolites in the tryptophan catabolic pathway. LNAA-mediated transport of kynurenines concentrates peripheral tryptophan metabolites in the central nervous system.
Neuroendocrine Influences
The changing bio-availability of tryptophan has significant influence on neuroendocrine function. The rate-limiting step in the synthesis of the brain neurotransmitter serotonin is the conversion of tryptophan to 5-hydroxytryptophan by tryptophan hydroxylase (with tetrahydrobiopterin -- a form of folic acid -- as co-factor).
Under normal conditions, tryptophan hydroxylase is not saturated (filled with substrates), so extra tryptophan increases serotonin synthesis. This sensitivity of serotonin production to tryptophan availability appears to be biologically optimized. Under average conditions, a large percentage of the tryptophan hydroxylase is not saturated and therefore available for tryptophan binding.
It has long been recognized that tryptophan-deficient diets lead to depletion of brain serotonin and disturbance in serotonergic neural function, but now it is becoming recognized that normal physiologic variations in plasma tryptophan produce biologically significant variations in serotonin synthesis.
Tryptophan metabolites play other physiologically important roles. Picolinic acid, a product of tryptophan's oxidative metabolism, is involved in the normal intestinal absorption of zinc. Quinolinic acid itself has been reported to be involved in the regulation of gluconeogenesis.
Tryptophan and AIDS
Abnormalities of tryptophan metabolism have been observed in both monkeys with simian retrovirus type-D (SRV-D) and humans with HIV infections.
Simian retrovirus infections are associated with the same immunodepression, T4-cell-count reductions, neoplasms, and opportunistic infections that occur in human AIDS. Heyes et al. [1989] have found that cerebrospinal fluid quinolinic acid concentrations are increased in SAIDS. This observation has been confirmed in human AIDS patients.
The concentration of quinolinic acid present in HIV and SRV-D infections is sufficient for it to function as an excitotoxin to NMDA neuroreceptors.
During opportunistic infections, quinolinic acid levels can rise even further. Overstimulation of NMDA receptors is known to interfere with long-term learning and may account for some of the cognitive deficit seen in AIDS dementia.
Interferon-Gamma
The regulation of tryptophan availability during infection is largely mediated by interferon-gamma (IFN-gamma). IFN-gamma induces IDO in peripheral blood monocytes and their derived macrophages and has an anti-proliferative effect on tumor cells [Ozaki, et al., 1991].
Tryptophan and kynurenine metabolites have been reported to be essential for the IFN-gamma-mediated activation of macrophage tumor-cell killing [Leyko and Varesio, 1989]. Increased IDO may be contributed by mature (differentiated) tissue macrophages rather than from pluripotent (undifferentiated) monocytes (see Forefront #32 for more information).
The actions of type-I IFNs (IFN-alpha and IFN-beta) are antagonistic to IFN-gamma. Modulation of IFN-gamma influence by type-I IFNs may represent feedback control of immune response and an immunoregulatory function of cytokines.
Long-term expression of IFN-gamma and IDO may represent a failure of immune feedback control. Dr. Ozaki and colleagues state, "It is conceivable that the overexpression of IDO and elimination of the least abundant amino acid tryptophan may be more harmful than beneficial to the integrity of macrophages."
IDO increases one hundred fold during viral infection, endotoxin (lipopolysaccharide) shock, or interferon administration. During this stress reaction, tryptophan catabolism is markedly enhanced. Kynurenine and xanthurenic acid increase several-fold.
This negative influence may become critical in unresolved long-term infections.
In cell cultures, tryptophan depletion has been found to be the mechanism by which IFN-gamma acts against replication of such parasites as Toxoplasma gondii, Chlamydia trachomatia and Clamydia psittaci. Supplemental tryptophan reverses this inhibition [Brown, et al., 1991].
The antiproliferative effect of IFN-gamma against several human tumor cells also depends on the tryptophan-deprivation mechanism.
In mice, transplanted tumor cells exhibit a marked increase in IDO induction during rejection from the host. The host cells infiltrating the transplanted tissue show no such increase. The active agent affecting this process is IFN-gamma [Takikawa, 1991].
Tryptophan and Monocytes
While tryptophan deprivation is engineered by IDO induction, there may be other mechanisms involved. Serum tryptophan falls significantly in only 2-4 hours, long before IDO induction is observed in vitro.
Preliminary tryptophan deprivation through absorption into mononuclear cells may be the initial mechanism [Finocchiaro, et al., 1988].
Tryptophan Metabolism in Chronic Diseases
Cancer patients given type-I and II interferons experience a 50-80% decrease in serum tryptophan and a 5-500% increase in urinary kynurenine metabolites.
Tumor cells transplanted into allogeneic (genetically different) mice produce large amounts of IDO when being rejected by the host animal. No such IDO production occurs in the infiltrating host immune cells or when tumor cells are transplanted into syngeneic mice.
Human lung-cancer patients have been reported to have significantly elevated IDO levels in their lung tissue compared to normal tissue [Yasui, et al., 1986].
These observations support the hypothesis that IFN-gamma-induced tryptophan restriction is an in vivo antitumor mechanism [Takikawa, et al. 1991].
Patients with autoimmune disease exhibit increased IFNs and tryptophan metabolites.
Although there is some disagreement in the literature about IFN levels with these diseases, many of the factors known to be associated with IFN production are evident (increased neopterin, elevated serum beta-2-microglobulin, and increased tryptophan metabolites).
Cells isolated from synovia (joint membranes) of rheumatoid arthritis patients have been reported to exhibit increased IDO activity, even though IFNs are not usually detected in general circulation.
Such observations suggest that IFN expression and IDO induction can be extremely localized. Despite localization, this tryptophan depletion likely contributes to the degeneration, wasting and other symptoms of these diseases.
IFNs are also increased in HIV disease; the higher the levels the worse the prognosis [Brown, et al. 1991]. Tryptophan and serotonin are depleted and kynurenine and quinolinic acid are elevated. This excess may account for the cachexia, dementia, diarrhea and some of the immunosuppression of AIDS.
Theoretical Questions about Intervention
In many respects, AIDS resembles classic pellagra caused by niacin/tryptophan deficiency. But is tryptophan supplementation equally appropriate in AIDS?
Is there any long-term survival value in continued tryptophan restriction during unresolved chronic infection or autoimmune disease?
How toxic are tryptophan's metabolites?
How significant are the neuroendocrine deficits caused by long-term tryptophan deprivation?
To Treat or Not to Treat
Given the known adverse influences of some IDO-induced tryptophan metabolites, supplementing tryptophan may be an inappropriate strategy.
Even if tryptophan and its metabolites inhibit IDO, increased substrate availability might result in increased quinolinic acid production.
The possible neuroendocrinological benefit of increasing endogenously produced serotonin and melatonin might be offset by simultaneous increased production of quinolinic acid and exacerbation of the excitatory insult.
Tryptophan Derivatives
As alternatives to tryptophan, 5-hydroxytryptophan (5-HTP), serotonin, N-acetylserotonin and melatonin may be used to fortify the serotonergic nervous system.
These chemicals are not able to function as substrates for IDO and may be able to stabilize neuroendocrine function without excitatory side effects.
Oral use of 5-hydroxytryptophan in humans has been studied. In obese adult women, 300 mg of 5-HTP 30 minutes before eating produced an anorexic influence and early satiety during the meal [Cangiano, et al., 1991]. Nausea was reported in 70% of the women, but this had disappeared 6 weeks into the study.
Despite the unwanted anorexic influence of 5-HTP in patients with wasting syndromes, 5-HTP therapy may be beneficial in patients with elevated IDO activity.
Administration of 5-HTP 30 minutes before eating is designed to optimize its adverse effect on appetite. Administration of 5-HTP 30 minutes after eating may avoid this consequence. Additionally, obese and lean people may react oppositely to serotonergic stimulation.
Melatonin has also been studied in people as a remedy for jet lag. Melatonin is a neurohormone produced from serotonin by the pineal gland, a neuroendocrine gland closely involved in regulation of the biological circadian (daily) rhythm.
Melatonin release is periodic, triggered by environmental factors relating to the cessation of light exposure. In normal, healthy people, melatonin release begins shortly after it gets dark, increases for several hours, peaks in the early hours of the morning and then drops back to minimal levels by sunrise.
Melatonin deficits are known to cause sleep disturbances and may be responsible for some of the cognitive deficit seen in jet lag. Oral melatonin, in 5-10 mg doses, is able to rapidly and efficiently correct jet-lag-induced cognitive impairment.
The same doses in HIV patients have produced anecdotal reports of improved quality of sleep and feelings of well-being. No significant side effects were noted with melatonin use at this dose.
IDO Strategies Inhibition of IDO may also be a good therapeutic strategy. Tryptophan catabolism in the liver is known to be feedback-inhibited by intermediates and products of the tryptophan degradation pathway, like NAD and NADH.
IDO may function similarly. NADH carries hydrogen and perform reducing (anti-oxidizing) functions in cellular metabolism. Perhaps it is the reducing power that NAD and NADH provide which inhibits IDO.
Oxidation reactions are known to trigger immune activation. Oxygen free radicals interact with the FFAs (like arachidonic acid) to produce prostaglandins, tissue hormones which induce inflammation, fever, and immune activation.
Macrophages release oxygen free radicals (superoxide and hydroxyl radicals) when they come in contact with their antigen targets. Antibodies themselves may be more reactive in an oxidizing environment, and the elevated temperature of fever promotes free-radical reactions.
Oxidizing conditions, then, appear to be the on switch for immune activity. Do reducing conditions turn it off?
The best clinical method of supplementing reducing power is intravenous ascorbate (vitamin C) [Cathcart, 1991]. Each ascorbate molecule is capable of donating 2 hydrogen atoms, and doses of up to 200 grams per 24 hours have been given without serious side effects.
Such doses have shown the ability to dramatically arrest the clinical course of several life-threatening autoimmune diseases [Cathcart, 1992].
The maximum tolerated oral dose of ascorbate is limited by intestinal absorption, causing diarrhea when bowel tolerance is exceeded.
Interestingly, the vitamin C bowel-tolerance dose escalates with the severity of the disease: 4-15 grams in healthy people, 30-100 grams in people sick with colds, and 100+ grams in people sick with serious viral illnesses like influenza and mononucleosis [Cathcart, 1985].
Perhaps the bowel tolerance dose of vitamin C directly tracks the degree of oxidation in the body.
Interferon Strategies Because IFN-gamma triggers IDO, antiIFN-gamma agents might be effective in decreasing IDO expression. IFN-gamma antibodies have been used in scientific cell-culture experiments, but they have not yet been investigated in clinical trials with humans.
IFN-alpha and IFN-beta (Type-I IFNs) are known to antagonize IFN-gamma (Type-II IFN) activity in lymphocytes. Several forms of IFN-alpha are available in the world drug market.
Endogenous production of IFN-alpha can also be encouraged. Multi-gram doses of vitamin C are known to stimulate IFN-alpha production.
Conclusion Abnormalities in tryptophan metabolism are widespread in AIDS and autoimmune disease. These abnormalities contribute to neurodegenerative processes, cognitive impairment and immune incompetence.
There are numerous possible interventions which might ameliorate these effects, many of which are of a low order of toxicity. Further research into this area is badly needed.
Click on ``back'' or the home page. References R. R. Brown, Y. Ozaki, S. P. Datta, et al., Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS. In: Kynurenine and Serotonin Pathways, R. Schwarcz, et al., (Eds.), Plenum Press, New York, 1991.
C. Cangiano, F. Ceci, M. Cairella, et al., Effects of 5-hydroxytryptophan on eating behavior and adherence to dietary prescriptions in obese adult subjects. In Kynurenine and Serotonin Pathways, R. Schwarcz, et al., (Eds.), Plenum Press, New York, 1991.
R. F. Cathcart, Vitamin C: the nontoxic, nonratelimited, antioxidant free radical scavenger. Medical Hypotheses 18: 61-7, 1985.
R. F. Cathcart, A unique function for Ascorbate. Medical Hypotheses 35: 32-7, 1991.
Robert Cathcart, M.D., personal communication, February 1992.
L. M. E. Finocchiaro, E. S. Arzt, S. Fernandez-Castelo, et al., Serotonin and melatonin synthesis in peripheral blood mononuclear cells: Stimulation by interferon-gamma as part of an immunomodulatory pathway. Journal of Interferon Research 8: 705-16, 1988.
M. P. Heyes, D. Rubinow, C. Lane, and S. P. Markey, "Cerebrospinal fluid quinolinic acid concentrations are increased in acquired immune deficiency syndrome. Ann Neurology 26: 275-77, 1989.
M. P. Heyes, M. Gravell, M. April, et al., Quinolinic acid concentrations are increased in cerebrospinal fluid of rhesus macques (macaca mulatta) naturally infected with simian retrovirus type D. In: Kynurenine and Serotonin Pathways, R. Schwarcz, et al., (Eds.), Plenum Press, New York, 1991.
M. P. Heyes and B. J. Quearry, Increased L-tryptophan, 5-hydroxyindoleacetic acid, 3-hydroxykynurenine and quinolinic acid concentrations in cerebral cortex following systemic endotoxin administration. In: Kynurenine and Serotonin Pathways, R. Schwarcz, et al., (Eds.), Plennum Press, New York, 1991.
M. A. Leyko and L. Vareso, Role for tryptophan and its metabolites in the activation of macrophage tumor cytotoxicity. FASEB J. 3: A822, 1989.
Y. Ozaki, E. C. Borden, R. V. Smalley, and R. R. Brown, Interferon type I and II antagonism: A novel regulatory mechanism of indoleamine dioxygenase induction in human peripheral blood monocytes and peritoneal macrophages. In: Kynurenine and Serotonin Pathways, R. Schwarcz, et al., (Eds.), Plennum Press, New York, 1991.
J. C. Peters, Tryptophan Nutrition and Metabolism: an Overview. In: Kynurenine and Serotonin Pathways, R. Schwarcz, et al., (Eds.), Plenum Press, New York, 1991.
Q. R. Rogers, The nutritional and metabolic effects of amino acid imbalances. In: Protein Metabolism and Nutrition, D. J. A. Cole (Ed.), Butterworths, London, 1976.
R. Schwarcz and F. Du, Quinolinic acid and kynurenic acid in the mammalian brain. In: Kynurenine and Serotonin Pathways, R. Schwarcz, et al., (Eds.), Plenum Press, New York, 1991.
O. Takikawa, A. Habara-Ohkubo, and R. Yoshida, Induction of indoleamine-2,3-dioxygenase in tumor cells transplanted into allogenic mouse: interferon-gamma is the inducer. In: Kynurenine and Serotonin Pathways, R. Schwarcz, et al., (Eds.), Plenum Press, New York, 1991.
E. R. Werner, G. Bitterlich, D. Fuchs, et al., Human macrophages degrade tryptophan upon induction by interferon-gamma. Life Sci. 41: 273-280, 1987.
E. R. Werner, D. Fuchs, A. Hausen, et al., Tryptophan degradation in patients infected by human immunodeficiency virus. Biol. Chem. HoppeSeyler 369: 337-40, 1988.
H. Yasui, K. Takai, R. Yoshida, and O. Hayaishi, Interferon enhances tryptophan metabolism by inducing pulmonary indoleamine-2,3-dioxygenase: Its possible occurrence in cancer patients. Proc Natl Acad Sci USA 83: 6622-26, 1986.
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TerryK
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Maybe this is partly what happens in those with lyme who go on to develop ALS? More QUIN?? Probably other things too but very interesting.
Implications for the Kynurenine Pathway and Quinolinic Acid in Amyotrophic Lateral Sclerosis
Gilles J. Guillemina, Vincent Meiningerb, Bruce J. Brewc
aCentre for Immunology and University of New South Wales, School of Medicine and School of Medical Sciences, Sydney, Australia;
bCentre SLA Salp�tri�re F�d�ration de Neurologie, l'H�pital de la Piti�-Salp�tri�re, Paris, France; cSt. Vincent's Hospital, Department of Neurology, Sydney, Australia
The kynurenine pathway (KP) is a major route of L-tryptophan catabolism leading to production of several neurobiologically active molecules.
Among them is the excitotoxin quinolinic acid (QUIN) that is known to be involved in the pathogenesis of several major inflammatory neurological diseases.
In amyotrophic lateral sclerosis (ALS) degeneration of motor neurons is associated with a chronic and local inflammation (presence of activated microglia and astrocytes).
There is emerging evidence that the KP is important in ALS. Recently, we demonstrated that QUIN is significantly increased in serum and CSF of ALS patients.
Moreover, most of the factors associated with QUIN toxicity are found in ALS, implying that QUIN may play a substantial role in the neuropathogenesis of ALS.
This review details the potential role the KP has in ALS and advances a testable hypothetical model.
Copyright � 2005 S. Karger AG, Basel
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TO LIFE
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Dear Terry,
If your up for it, maybe you could email Dr. Guillemin and just to see if he even believes in Lyme Disease.
Dr. Gilles Guillemin Centre for Immunology, St. Vincent's Hospital Darlinghurst, NSW 2010 (Australia) Tel. +61 2 8382 2835, Fax +61 2 8382 2391 E-Mail [email protected]
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TerryK
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Thanks for the suggestion TL. I don't have the ALS presentation and I need to concentrate on other things right now.
I think increased QUIN happens in many infections from what I've seen. It could happen in many other situations too for all I know. I see no point or benefit to myself in contacting this person.
Perhaps you should contact him if you are interested?
Terry
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TerryK
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In 1996 I gave a talk on neurological Lyme disease to the Upper Peninsula Michigan Health Department.
A large part of that talk was about quinolinic acid, a neuro-toxin that is produced in both Lyme patients and M.S. patients as a result of macrophage activation in the CNS. (Quinolinic Acid production and myelin destruction is a very specialized form of inflammation in the brain that does not involve lymphocytes as part of the inflammation process. Inflammation in the peripheral system is quite different and involves many more elements including lymphocytes, neutrophils, lymphokines, histamines, vasoactive amines, fibrinogen, bradykinin, prostaglandin synthesis, and other cascade events not often seen in the M.S. or Lyme patient's brain.)
(In acute advanced neuro-Lyme and M.S. the levels of Quinolinic Acid are at similar levels in both patients and about 40x the normal levels. Quin-Acid is the cause of dementia in AIDS patients where levels can exceed 200-400 x normal and result in a comatose state.)
..... There is more but not related to quinolinic acid
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TerryK
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http://tinyurl.com/mtbmkb Inhibitors of the kynurenine pathway, 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilic acid, attenuated [13C6]QUIN formation by macrophages,
LN is one of many infectious and immune mediated pathophysiological processes that contribute to diseases and mental illnesses. This term is an acronym that can be abbreviated as '' IIMPP.''
Although it is clear that Bb. causes considerable neural dysfunction, the exact pathophysiological process is a subject of current research. Proposed pathological mechanisms which contribute to the neural dysfunction associated with LN include vasculitis, direct cell penetration, toxin release, cytokine effects, inflammation and excitotoxicity mediated by quinolinic acid and kynurenine (14).
Adequate conversion of tryptophan into serotonin within the CNS is considered to be highly significant for emotional stability. Depression, suicide, violence, obsessive compulsive disorder and fear and anxiety disorders are associated with reduced serotonin levels. It has also been demonstrated that reduced levels of 5-HIAA (a metabolite of serotonin} in the cerebral spinal fluid is associated a high risk of suicide attempts and impulse control disorders in convicted murderers (34).
There appears to be reduced conversion of tryptophan into serotonin within the CNS in a number of infectious diseases that affect the brain, including LN (35). Instead of converting to serotonin, there is increased conversion of tryptophan into quinolinic acid and kynurenine in LN (36). These two alternative metabolites of tryptophan are excitatory, and can contribute to excitatory neurotoxicity. In an animal model, kynurenine and quinolinic acid caused behavioral shifts associated with aggression, consisting of limb hyperkinesis, emotional strain, malice, fear, aggression with snarling and hissing and attack on provocation. It was suggested by the authors that kynurenines and quinolinic acid can participate in the generation of disorders peculiar for epilepsy (37).
-------------------------------------The article is much larger
THESE ARE MY COMMENTS NOW Seems like at the least, lyme patients should be taking the Buhner supplements that I listed above in order to protect and repair their brain from the effects of quin. I've been taking all but resveratrol for several years.
Bea mentioned in one of her posts that Buhner said that resveratrol blocks the conversion of tryptophan to kynurenines and quin so I think I may start taking that.
My hope is that this would allow tryptophan to be converted to serotonin but at the very least, it should help keep kynerenine and quin at bay until the brain infection is under control.
Based on lab tests I know that kynurenines and quin are high in me. I've read that it is hard to accurately measure quin in the blood so maybe mine is even higher than reported.
According to Buhner, without specific therapy to protect the brain from Quin and stimulate repair of damaged areas, the damage is unlikely to correct. Abx alone do nothing to protect or help regenerate damaged areas.
I'm not a doctor, please check any changes to your supplements with your doctors.
Marnie - I've thought for a long time that getting inflammation down was critical to effective treatment but also keeping the immune system in TH1 mode and dealing with biofilms - then add the abx. I'm ordering magnesium oil to see if that might help as well based on what you've said about magnesium.
So now that I've done what I said was inappropriate and taken the thread off in another direction, I'll go back to oleic acid.
You wrote: Now, in researching Alzheimer's, I found the Omega 9 called oleic acid in coconut oil can help reverse AD. It appears to increase PPARY (which is deficient in sarcoidosis) too.
I'm really interested in this. My mother was diagnosed with atypical sarcoidosis. I've been taking monolaurin off and on for years but have not taken oleic acid as a medicine. Will be back next week when I'm back from LLMD visit to learn more about oleic acid and why it might work.
Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Terry, you and I share similar knowledge/understanding. We have found many of the same puzzle pieces.
Our macrophages metabolize L-Tryptophan to quin., but quin converts to niacin which Bb (and we need).
Since Mg is needed to make all enzymes and Mg is low, does this impact the level of the enzyme to convert quin to niacin?
Our reaction to lyme is almost as if the body downregulates the defense system as it does to preserve a fetus. Pregnancy may -> an even greater downregulation of the immune system (= remission).
Seek...I didn't mean to ignore you...I got "side-tracked" and upset by the other posts.
To Life...I'm positive I do not have lyme as I did Rife (using a $6,000 machine which sends the frequencies thru a light)
as a personal experiment
after doing a LOT of research on it.
I had no reaction (herx) to one minute at 432Hz (Rife lyme frequency). NONE.
Lyme patients have a big reaction to that frequency.
I also did an ozone sauna. I can tell you what it is like to do an ozone sauna from a personal perspective.
Someday I will try hyperbaric...to see what I feel like afterward.
To Life you said, "Marnie has brought up Drexel"
What? Drexel? I have never ever heard of it! Honest.
Klutzo...rebalancing the neurotransmitters in severe depresion is really an "art". The reality is ....very few psychiatrists know how to do that. It involves trying various anti-depressant combinations, modifying doses if needed and/or adjusting the timing.
This doesn't always lead to weight gain (though some people who were very depressed, when treated, will regain the weight he/she lost.
For sure, it is a chemical imbalance and one that can even be SEEN on a MRI (short video):
Once someone suffers severe depression even after they recover, they can slip back easily.
Sometimes people who have had several episodes of depression (periodically over years) need to be put on low dose maintenance anti-depressants ongoing to help prevent the recurrence of a major depressive episode.
I don't know if it would help or not, but when you have a negative thought, write it down and then follow it up with a positive/humorous thought.
Like:
"I hate being fat."
"Well...look at the surgeon general of the U.S. I'm following her example. Being fat apparently IS healthy!"
BTW...over our door which goes out to our pool, I have a sign that reads: "I don't skinny dip. I chunky dunk."
A joke in the current Readers' Digest (Sept. issue) puts normal female weight gain in perspective:
"My sister and I decided to reframe a favorite photograph of our mother and father from when they were dating, some 60 years ago.
After removing the picture from the frame, I turned it over, hoping to find a date. I didn't. Instead, my mother had written, "128 lbs."
[ 08-22-2009, 04:16 AM: Message edited by: Marnie ]
Posts: 9481 | From Sunshine State | Registered: Mar 2001
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Oh...you are right...I didn't recognize "Drexel" and have no idea where it is...actually I had never heard of that college (edu), but was impressed that he is an assoc. professor of the Department of Neurobiology and Anatomy
I figured if he holds the above appointment, he must be quite intelligent.
His animation (photon - energy transfer) is really easy to understand. I commend him for that!
Sorry...I don't know anything about RSD...did a quick search...
I do remember my sis told me she knew of a lyme patient in NY who was so skin sensitive, he couldn't stand to wear clothing. He found anything touching his skin intolerable.
I know absolutely nothing about the validity of this, but do find it curious:
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