B-12 - The Hidden Story

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Since B vitamins are water soluble and stay in your body a short time, you might want to take a low dose B complex 2 or 3 times a day rather than a high dose on once a day.
hmmm. I open the capsules and separate the doses with some other things, maybe I can try that with B vitamins. I hope they don't taste too nasty.
Is there a vitamin B panel which labs can do? I know you can check B12 and folate, but is there a test for the others? That would give a better idea of what I actually need. B6 is the main one I'm suspicious about, since it's related to hair loss and dry skin on the sites I read. Almost a month into using B12 and my hair is still falling out in handfuls whenever I shampoo. So I'm still missing something. Or maybe I'm expecting too much too fast.
As far as safety, if I simply add in a B complex, other than Freddds paradoxical folate deficiency, is there anything to watch out for, or are they pretty non-toxic?
 

Lotus97

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hmmm. I open the capsules and separate the doses with some other things, maybe I can try that with B vitamins. I hope they don't taste too nasty.
Is there a vitamin B panel which labs can do? I know you can check B12 and folate, but is there a test for the others? That would give a better idea of what I actually need. B6 is the main one I'm suspicious about, since it's related to hair loss and dry skin on the sites I read. Almost a month into using B12 and my hair is still falling out in handfuls whenever I shampoo. So I'm still missing something. Or maybe I'm expecting too much too fast.
As far as safety, if I simply add in a B complex, other than Freddds paradoxical folate deficiency, is there anything to watch out for, or are they pretty non-toxic?
B complex doesn't taste too good, but if you're only taking 1/4 of a capsule it shouldn't be bad. The standard tests for folate and B12 won't do you much good. I don't remember the reason why. You're not going to find a B complex without folate. You're better off just dividing up that Swanson's bcomplex into multiple doses. That would be the cheapest solution.
 

EtherSpin

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Chocolate is a funny one. It's commonly written that chocolate cravings mean, one needs magnesium. I still had cravings even when I was taking Mg. I know there are plenty of mood elevating chemicals in chocolate, but, there is also alot of copper. Most of what we read about copper is negative, but the good news about it is that it's important for cardiovascular function, etc.
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I don't follow the idea that cravings are necessarily an indicator of what the body needs (when you don't already consciously know "X" food helps "Y" symptom) - at least not often enough to be reliable, chocolate cravings also come because we are wired for sugar from fruit consumption and wired for fat consumption via evolution during famine and cocoa is rich in cocoa butter - also it contains at least 2 potent stimulants (caffeine and theobromine) and some mood enhancers so we could be seeking all kinds of physical responses via a chocolate craving and in the modern world the sugar and fat are no longer valid cravings for survival . cravings are a mixed bag, hard to rely on I reckon :)
 

Lotus97

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I don't follow the idea that cravings are necessarily an indicator of what the body needs (when you don't already consciously know "X" food helps "Y" symptom) - at least not often enough to be reliable, chocolate cravings also come because we are wired for sugar from fruit consumption and wired for fat consumption via evolution during famine and cocoa is rich in cocoa butter - also it contains at least 2 potent stimulants (caffeine and theobromine) and some mood enhancers so we could be seeking all kinds of physical responses via a chocolate craving and in the modern world the sugar and fat are no longer valid cravings for survival . cravings are a mixed bag, hard to rely on I reckon :)
I usually find dark chocolate very satisfying and have no urge to eat much of it. High fructose corn syrup on the other hand is bad news. BTW, naturally occurring sugar in fruit is levulose not fructose.
http://www.the-healthy-diet-paradise.com/HFCS.html
High Fructose Corn Syrup And Obesity
Our brains do not recognize fructose. High fructose corn syrup confuses ghrelin, which is the hormone that says when you are hungry. HFCS also disrupts leptin production, which is the "I'm full" hormone. When working properly, these hormones in the brain bounce off of each other creating a normal hunger, eating, satisfaction experience. High fructose corn syrup inhibits this process.
This abnormal reaction in your system can create explosive, unceasing hunger pangs and lead to morbid obesity. Fructose consumption increases appetite and body weight. Fructose makes your brain believe that it is starving.
The liver processes fructose very differently than it does glucose and other sugars. When acute fructose is introduced, Dr. Lustig in "Sugar, The Bitter Truth," states, "There's no transporter for fructose on the beta cell that makes insulin."
Since HFCS does not stimulate insulin very much, it confuses the centers of the brain which controls leptin production. The very thing to set the stage for leptin to work is the release of insulin in the first place.
Since insulin is not secreted, our leptin does not go up either. Leptin is a hormone produced by our fat cells that tells us to stop eating. The brain literally cannot read that it has eaten anything. So in a very real sense, fructose stimulates hunger.
 

Lotus97

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Can B12 cause wiredness for reasons other than excitoxicity from overmethylation? If so, what's causing it? If it is excitoxicity does Niacin not always work? Because it doesn't seem to help me.
 

Freddd

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Can B12 cause wiredness for reasons other than excitoxicity from overmethylation? If so, what's causing it? If it is excitoxicity does Niacin not always work? Because it doesn't seem to help me.
Hi Lotus,

I'll take a try on that. It makes all sensory phenomina more intense. It speeds up the nerve transmission speed. It is essential for the nerves to function properly and it appears to turn up the voltage in the nervous system making all of its defects more obvious and intensse. MeCbl protects against neural toxicity, not casue it. The excitotoxicity hypothesis is another one of those words that leads to non-working hypothesis becasue it is misapplied so often. People who have neurologcal brightening are generally those that heal substantially if they follow the clues. It enables us to be aware of anything that increases healing very obvious. Becasue of that trials that might have taken months to even have a hint were often definite in 24 hours. I was able to test multiple items very quickly.
 

Lotus97

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I'm afraid we're going to have to agree to disagree about excitoxicity. Rich warned against taking high doses of methylcobalamin along with high doses of methylfolate since that could overdrive the methylation cycle leading to excitoxicity among other things. There's no need to rehash that argument. I posted my question because I wasn't sure that was what was causing my symptoms.

Many people here are simply fatigued, but many also experience symptoms of physical anxiety or wiredness. In most cases, this is before any methylation supplements are taken. There are several threads devoted to this subject so I know it is not uncommon in this community. We are already suffering from sensory overload so the last thing we want is to increase this. Simply increasing a person's energy does not always translate into more healing. I find it difficult to stay off the computer most of the time yet I know I need to stay in bed for much of the day in order to heal. This isn't an argument against methylation, but different people are going to need to take different approaches.
 

Freddd

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You asked a question. MeCbl causes multiple sensations that might be called wiredness for multiple reasons. This is why I asked you to define the symptoms of "over methyaltion". For that matter, define "excitotoxicity" in terms of the symptoms, what makes it come on and of course how to get rid of it. When a person can make symptoms come and go they understand it in a practical usable sense. Until that it is all theory. If the theory doesn't lead to being able to treat it effectively the theory is usually quite wrong becasue it doesn;'t convey anything useful. "Excitotoxicity" theory doesn't lead to healing but rather prevents it generally. "Overmethylation" theory doesn't lead to healing but sure does prevent healing., in my experiencse and opinion. They lead to choices that don't enable healing as they are typically applied. As these theories are often pushed by a variety of practitioners, often requiring all sorts of visits and treatments that need monitoring. As an "inside man at the skunk works" (group health consulting, working for plan trustees, the members), I got to help detect all the docs that are removed from panels for abusive and fraudelent behavior. As "fraud" per se is almost impossible to prove and the feds don't step in until the amount reachs some millions of dollars, the insurers and groups quietly remove them from the PPO panel and sometimes sur them if the evidence is good. Different standard, fraud doesn't have to be proved, just unearned moneys have to be proved. Their patients might have more second opinions suggested or required in a managed health care situation. One of the things we looked for are the docs who turn patients who never get better, into an annuity with all sorts of dubious treatments that never seem to deliver the suggested results, or at least not very often, and frequently have some preety bad outcomes. I went through all this personally too trying to chase down my problems. I wasted $200,000 over 20 years pursuing every theory in the books. I had all the same ideas suggested. These are not new ideas. They go back 40 to 50 years or longer. Insurance doesn't support total amalgam removal for instance. In fact that is usually considered abusive and the person often gets worse or has no positive changes. Also the way it is done is often in violation of standards of care and standards of safety.

The people that are anxious to start with have a very different set of responses that often trigger all sorts of uncontrollable limbic emotions. Anxiety, panic, fear, rage, anger and others can all be of limbic stimulation results. In the model I am using carnitine or AdoCbl are usually the most extreme. MeCbl to the extent a person converts it to AdoCbl also has these effects. These emotions/moods/personality traits appear to get triggerred when the mitochondria in some part(s) of the limbic sysrtem start producing ATP and affect dopamin. It is hypothecized by researchers looking at all this that limbic system damage accumulates over decades of poor Mito funtioning that elevates MMA in the cerebral spinal fluid while having low cobalamin in the CSF. When a person is deadlocked on carnitine then these emotions are most controllable because of the pharmacodynamics of carnitine. When the deadlock is AdoCbl (MeCbl possilbe) once the AdoCbl enters the mitochondria it stays there for the apparant life of each michondrion so day by day control isn't possible.

At least this hypothesis can be demonstrated and symptoms increased ot decreased by how various supplements are taken. It is a more predictive and useful hypothesis than "excitotoxicity" being caused by MeCbl which is protective against glutatmate toxicity which is actually does over stimulate neurons and can cause neuron death. Also MeCbl prpotects against the toxins released by the nerons when they die that then produces cascading neuron death. Now I didn't just make this up oin the spot for you. It's in the peer reviewed journal articles written in the past 10-20 years when most of the MeCbl research is done. Physiological psychology is very involved in all this. Damage produced by non-functioning mitochondria (causing elevated CSF MMA) has serious consequences when not recognized and stopped. So far there is no known way much less proven way to stop or repair that damage and it keeps getting worse.

I have been reasonably successful at slowing or stopping my CNS neurological damage and even reversing it substantially. The CNS damage I have is not to the limbic system, but to other areas. There sure appear to be some damaging neurological things going on as exemplified in the symptoms and responses to these supplements. You can call it "excitotoxicity" if you like but it won't lead you to anything useful. Semantics and general semantics, meanings of words and meaning of meanings can keep a person trapped. If you wanted a more meaningful description, perhaps it could be called "excitotoxicity" in the limbic system with MMA (from mito failure) as the irritant-footprint and when the damaged/irritated nerves are stimulated by ATP (and dopamine?) the irritated nerves produce all sorts of unendurable symptoms.



MMA symptoms in the body:

Drowsiness
Seizures
Lethargy
Failure to thrive (lack of tissue formation, tissue breakdown)
Recurrent vomiting
Dehydration
Respiratory distress
Reduced muscle tone
Enlarged liver
High levels of methylmalonic acid in blood
High levels of methylmalonic acid in urine
Metabolic acidosis
Increased levels of acetone in blood
Elevated blood ammonia level




acute neurological changes: decreased cognitive performance; confusion; dementia; delirium; myelopathy; and tremor. Only one late-onset patient had pigmentary retinopathy - They may have progressive neurological deficits in spite of appropriate treatment.



Note added by me. “Appropriate treatment” is HyCbl in the references which of course doesn’t work well when AdoCbl/LCF is needed.



Complications:

Low blood sugar, Mental retardation, Chronic kidney disease, Pancreatitis, Coma, Death

So there we have the effects of a toxin. These neurological descriptions are general and are based on children to a large extent and overall body elevated MMA. There is no specific info I can find on purely localized CNS elevated MMA effect but as you see there is still a lot of neurological effect. I would continue the list with some of the adult forms of disease associated elevated CSF MMA; ALS, Parkinson’s.

Clearly ammonia and acetone in excess in the brain is toxic, Clearly MMA is damaging to the brain. Could this be the actual source of neural “Excitotoxicity”?
 

Lotus97

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Rich said if you try to push past excitoxicity you could be damaging neurons. Even if he's wrong, I prefer to be cautious. I do appreciate your explanation. I am trying to better understand this process. I have been taking a lot of ATP supplements for the past few years including everything in your protocol. I do remember you saying though that when you start methylation your supplements become more effective. When I was taking too much methylfolate I couldn't tolerate much coenzyme q10, but before that I was taking 400 mg a day. I think the dopamine angle is also interesting, because dbkita suggested norepinephrine could be part of my problem. The "anxiety" I experience is mostly physical though so I don't think calling it an emotion is accurate. My mind is relatively calm and my mood has been relatively good until recently. I'm sure ammonia is a significant cause of my wiredness since I eat over 100 grams of protein a day.
 

Freddd

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Rich said if you try to push past excitoxicity you could be damaging neurons. Even if he's wrong, I prefer to be cautious. I do appreciate your explanation. I am trying to better understand this process. I have been taking a lot of ATP supplements for the past few years including everything in your protocol. I do remember you saying though that when you start methylation your supplements become more effective. When I was taking too much methylfolate I couldn't tolerate much coenzyme q10, but before that I was taking 400 mg a day. I think the dopamine angle is also interesting, because dbkita suggested norepinephrine could be part of my problem. The "anxiety" I experience is mostly physical though so I don't think calling it an emotion is accurate. My mind is relatively calm and my mood has been relatively good until recently. I'm sure ammonia is a significant cause of my wiredness since I eat over 100 grams of protein a day.

Hi Lotus,

There is quite real excitotoxicity, glutatmate. And it does damage neurons. MeCbl however, protects against that not, causing it. What exact symptoms are you attributing to it?

What kind and how much carnitine are you taking and how are you taking it? That is a major determinant in this.

The "anxiety" I experience is mostly physical though

Can you explain that please.?
 

Lotus97

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Hi Lotus,

There is quite real excitotoxicity, glutatmate. And it does damage neurons. MeCbl however, protects against that not, causing it. What exact symptoms are you attributing to it?

What kind and how much carnitine are you taking and how are you taking it? That is a major determinant in this.

The "anxiety" I experience is mostly physical though

Can you explain that please.?
I think wired is the best way I can describe it. Other people here have used the same word and I think it's appropriate. I don't think my methylation supplements or any of my supplements are a big factor since I'm wired as soon as I get up in the morning. Not necessarily right when I wake up, but once I get out of bed and start doing things. It seems to be my body's way of coping with fatigue. I suspect it has something to do with my adrenals. Although I've had these periods in the past, the most recent one was triggered by B12. I was very tired and fatigued and started taking B12. It went ok at first, but once I raised the dose it was too much. The symptoms died down after stopping B12 for 3 weeks, but didn't go away entirely. After starting up again they haven't gotten much worse.

I am aware that methylcobalamin can protect against excitotoxicity, but it can also cause excitotoxicity. Even if Rich's theory as to why it happens isn't 100% correct both he and I have observed this phenomenon in others.
When people start doing the methylation block treatment, many of them experience an increase in symptoms that appear to be associated with excitotoxicity ("wired" feeling, insomnia, anxiety, hypersensitivity to light, sound and touch). This is associated with more rapid firing of action potentials by neurons that incorporate NMDA receptors. I've wondered for a long time why this gets worse when a person starts to lift the partial methylation cycle block.

O.K., here's what I suggest as the cause:

When a person has a partial methylation cycle block, they experience draining of their sulfur metabolites excessively down the transsulfuration pathway, because homocysteine is not being recycled back to methionine as rapidly as normal. Over the course of time, this depletes methionine somewhat, and PWCs tend to be low in methionine.

But even though this has occurred, there is still some draining down the transsulfuration pathway, and some of this serves to supply cysteine to make some glutathione. Glutathione is somewhat depleted, but some is still being made. If it weren't, the person would not survive.

O.K., now consider what happens when the activity of methionine synthase is increased by raising the availability of methylcobalamin and 5-methyl THF to this enzyme. All of a sudden, more of the homocysteine is recycled back to methionine, and therefore, less is available to the transsulfuration pathway. I suggest that this results in temporarily lowering glutathione even further! Over time, this situation will improve, and we have observed in lab tests that glutathione does come up to normal over a period of some months, on the average. However, initially, I suspect that it goes down, worsening the glutathione depletion temporarily.

Now here's how I think this impacts the excitotoxicity. Further glutathione depletion would increase the state of oxidative stress in the mitochondria of the neurons. This would intensify the partial blocks in the Krebs cycle and the respiratory chain, and that would further lower the rate of production of ATP. ATP is needed to power the membrane ion pumps in the neurons, and they normally maintain the electrical potential across the cell membranes.
This potential in turn determines the firing threshold for action potentials (nerve impulses). When the potential is lowered, the neurons become more sensitive and fire more readily. Thus, this results in increased excitotoxicity.

As you probably know, my views about dosing are somewhat different from Freddd's. In my view, based on the biochemistry and on seeing test results from three people with ME/CFS who have followed Freddd's type of dosing, this type of regimen causes overdriving of the methylation cycle and prevents glutathione from coming up. This is fine for Freddd and for others who may have his particular genetic variations (which I think are unusual), but not so fine for most people who have ME/CFS, in my opinion.

There seem to be more and more people who are exhibiting effects of overdriving the methylation cycle from taking high dosages of methylfolate and methyl B12 together. I do not recommend this approach.

Note that another effect of overdriving the methylation cycle is a further drop in glutathione, as less homocysteine is available to go toward cysteine synthesis.
 

Freddd

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I think wired is the best way I can describe it. Other people here have used the same word and I think it's appropriate. I don't think my methylation supplements or any of my supplements are a big factor since I'm wired as soon as I get up in the morning. Not necessarily right when I wake up, but once I get out of bed and start doing things. It seems to be my body's way of coping with fatigue. I suspect it has something to do with my adrenals. Although I've had these periods in the past, the most recent one was triggered by B12. I was very tired and fatigued and started taking B12. It went ok at first, but once I raised the dose it was too much. The symptoms died down after stopping B12 for 3 weeks, but didn't go away entirely. After starting up again they haven't gotten much worse.

I am aware that methylcobalamin can protect against excitotoxicity, but it can also cause excitotoxicity. Even if Rich's theory as to why it happens isn't 100% correct both he and I have observed this phenomenon in others.

Hi Lotus,

There is a subgroup of persons with "wired and tired". The lack of ATP for powring the cycle is why I suggest AdoCbl at the same time to ATP going. That often aliviates the the "tired" except that there is no more capacity. Both AdoCbl and LCF appear necessary to cause the mitochondria to grow new ones. I would propose that the sustained effect would be by partial mitochondria startup, becasue most other MeCbl effects are gone in a few days. The sustained "energy" appears to be ATP startup. One can top of with AdoCbl and that often has a energy startup that fades slowly. LCF is sometimes the omne that causes a huge startup requiring titration. Some people have a far more extreme startup and can try a microtititration from below any effectivness. Often people sensitive in a certain way are very bothered by ATP startup and call it overmethylation. This is a difficulty in language when this occurs because if the words don't convey what is happening. Also, if one is taking only 100mcg or so of MeCbl that is enough to sustain most healing but just doesn't provide much methyl. AdoCbl doesn't supply any methylation unless methylation was stalled on ATP block.
 
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Hope my post isn't interrupting the flow of your discussion. I just have a quick question...
I completed a month on Freddds protocol (I started with mB12, then a week later added Methylfolate, then few days later added l-car and Dibencozide, along with the multi, etc). Anyway, for the last week and half I've been developing bumps, about fingertip size, on my scalp. Very strange, as it was a symptom I had during a brief period as a child. Well, they are getting worse, I mean there are more of them. There is a sort of buzzy feeling in my scalp today as well.
Anyone know what this means???
 

Freddd

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Hope my post isn't interrupting the flow of your discussion. I just have a quick question...
I completed a month on Freddds protocol (I started with mB12, then a week later added Methylfolate, then few days later added l-car and Dibencozide, along with the multi, etc). Anyway, for the last week and half I've been developing bumps, about fingertip size, on my scalp. Very strange, as it was a symptom I had during a brief period as a child. Well, they are getting worse, I mean there are more of them. There is a sort of buzzy feeling in my scalp today as well.
Anyone know what this means???
Hi Adyia,

You have your clues. In my hypothesis healing has started more widely than can be maintained on the amount of methylfolate you are taking. As one titrates upwards, preferably by increasing number of doses first. At least 3 or 4 a day help maintain serum level. The feeling decreases and the bumps go away pretty quickly when you get enough methylfolate going, at least they do for me. Additional symptoms I get with this are sores at the corners of my mouth and IBS. Many people get mood changes pretty quickly and nausia is common, going towards more body pain, inflammation , asthma, allergies, MCS, etc. If you are taking injectable MeCbl and it has been exposed to light (now spoiled after not many minutes, it could cause the identical bumps just as quickly. See the symptoms lists of methylfolate insufficiency and low potassium becasue a person can have any blend of the two or all one ot the other, alternating until an overall balance is reached to support healing all the way arouind. Other shortages develop to but not quite as quickly. This is all about learning to follow the clues for taking each step. There is no single flow of conversation. There are many intertwined discussions added to branched from etc. Step in where it seems best. If you were to read http://forums.phoenixrising.me/index.php?threads/the-stages-of-methylation-and-healing.21725/ all those symptoms for those things will be near the beginning. Some others organizations of symptoms are near to being added to the end.
 

Lotus97

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Hope my post isn't interrupting the flow of your discussion. I just have a quick question...
I completed a month on Freddds protocol (I started with mB12, then a week later added Methylfolate, then few days later added l-car and Dibencozide, along with the multi, etc). Anyway, for the last week and half I've been developing bumps, about fingertip size, on my scalp. Very strange, as it was a symptom I had during a brief period as a child. Well, they are getting worse, I mean there are more of them. There is a sort of buzzy feeling in my scalp today as well.
Anyone know what this means???
If you are experiencing adverse effects from any type of treatment it is generally recommend to either lower your dose or stop for a few days. This quote from Rich might explain why this is happening to you:
One physician I know gives all his patients the methylation treatment, and then watches the response. If they experience some symptoms that appear to be caused by detox, but they are able to tolerate them, he continues with this treatment. If they have intolerable symptoms that appear to be related to mobilization of toxins, then he stops the methylation treatment and works on improving the status of the gut. When that is working better, he moves on to supporting the liver. His thinking is that the toxins that were being mobilized were being reabsorbed by the gut and sent back to the liver. In order to properly process and excrete the toxins, the gut and liver must both be functioning well enough to handle them.

My guess is that when there is an inflammation response to methylation cycle treatment, there is an infection. If the inflammation continues without resolution, then my guess is that the immune system has been reactivated, but is not capable of defeating an existing infection. In such cases, I think that treating to support the immune system would be one approach. Another would be to test to determine what pathogen is causing the infection, and then treating it with an antibiotic, antiviral or antifungal, depending on the pathogen.

I think it's important to note that a healthy person would not have any reaction to the supplements used in the methylation protocols, because their methylation cycle, detox system and immune system would already be functioning normally. So the fact that there is a response, even though it may seem to be deleterious, means that the methylation cycle was partially blocked and that these supplements were needed. However, the way one should proceed from that point on probably depends on the type of response that the individual person has.

So far, I'm pretty sure that if the following are present, they will need specific treatment, in addition to treating the methylation cycle partial block: biotoxin (including mold) illness, Lyme disease and its coinfections, well-entrenched viral infections, and high body burdens of toxic heavy metals, such as mercury. There may be others of which I'm not aware, but there is some experience with these, at least, which people have reported

I believe that the partial methylation cycle block is the pivotal abnormality in the pathogenesis and pathophysiology. With respect to the root cause or causes (etiology) of ME/CFS, I have suggested that this disorder arises from a combination of a genetic predisposition and some combination of a variety of stressors, which can be physical. chemical, biological, or psychological/emotional. I've suggested that this combination leads to glutathione depletion, which leaves B12 unprotected, which causes a decreased production of methylacobalamin, which inhibits methionine synthase, which forms a vicious circle with glutathione depletion, making ME/CFS a chronic condition. The retroviruses would fit within the biological stressors in my hypothesis, and certainly could be a root cause. If effective treatment of the retroviruses ends up bringing about recovery from ME/CFS, that will be very convincing as to its role as an etiologic agent. I hope that turns out to be the case for at least some of the PWMEs/PWCs. It may not be true for all of them, though, because this population seems to be very heterogeneous.

The reason I have included the variety of stressors as etiologic agents is that I have studied the published "risk factor" studies, and have also queried quite a few PWMEs/PWCs as to the events that preceded their onset, and I've found a variety of precursors. The common factor seems to be that they are all things that would be dealt with by the body's nonspecific stress response systems, and these in turn are known to place demands on glutathione.

In addition to this, there are now many PWMEs/PWCs who have taken the Health Diagnostics methylation pathways panel, and nearly all of them show evidence of a partial methylation cycle block or glutathione depletion, and usually both.

And when treatment was given in our clinical study that is directed toward lifting the partial methylation cycle block, we observed by testing that this does in fact occur, and that glutathione also comes up automatically. This was accompanied by improvement in symptoms in at least two-thirds of those who were treated.

Putting all of this together, I think the GD-MCB hypothesis is consistent with the observations and with known biochemistry and physiology. That doesn't mean that I believe that it is scientifically proven, which is a very high standard to meet, and requires considerable investment in time, money and effort, but that it is a valid working hypothesis. I'm hoping to interest researchers and fundors in this model so that it can be more thoroughly tested.

The methylation cycle is at the beginning of the sulfur metabolism. It is fed by methionine, which comes in as part of protein in the diet. Homocysteine is produced from methionine (via SAMe and SAH) in the methylation cycle, and then methionine synthase "decides" how much should be converted back to methionine, to stay in the methylation cycle. In the liver and kidneys, the BHMT reaction also converts some homocysteine back to methionine. The rest of the homocysteine enters the transsulfuration pathway, which is downstream.

The way that methionine synthase does its "deciding" is that the cobalt ion in the cobalamin that is its cofactor gets oxidized at a rate that depends on the state of oxidative stress in the cells. The more oxidizing this state is, the more often the cobalt ion gets oxidized, and that temporarily shuts down the methionine synthase reaction and diverts the homocysteine flow into the transsulfuration pathway, which helps to make more glutathione, which counters the oxidative stress. Unfortunately, in ME/CFS this delicate mechanism gets overwhelmed, and the oxidative stress becomes more severe, so that glutathione doesn't recover and get control of it. The result is that methionine synthase becomes partially blocked, and the sulfur metabolites drain down the transsulfuration pathway, into sulfoxidation, and get excreted too much as taurine and sulfate, which depletes methionine. The whole sulfur metabolism becomes dysfunctional, and that takes down the cell-mediated immune response as well as the detoxication system. As well, everything that depends on methylation reactions is affected, including gene expression, synthesis of several needed substances, and the neurotransmitter metabolism. Also, this drains the folates from the cells via the methyl trap mechanism, and that affects things that depend on folate, such as synthesis of new RNA and DNA. The latter is what cause the red blood cells to be too big and too few in number.

The methylation cycle is so fundamental to so many parts of the body's biochemistry that when it becomes dysfunctional, it causes a host of problems, and this is why people experience so many symptoms, involving so many body systems and organs, in this disorder.
 
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Lots of info to take in. Thanks for the input Lotus and Freddd.
I went to the doctor today (he is sooooo useless) and I saw my lab results from 3 months ago physical exam.
My hematacrit and hemoglobin are on the very low side (on previous lab tests the cut-offs were higher, and would've shown my HCT and HGB as too low). I've always had this anemia, every lab test all my life. Ferritin is always low for me as well, but this doc didn't test it, so I don't know my current level.
My doc's response to my low levels:
Low Creatinine "nothing to worry about"
Low Calcium "no big deal"
Low Alkaline Phosphatase "not a concern"
um doc, put it all together and maybe there is something going on??? Total waste of my time seeing him. I know all this protocol is supposed to be done under a doctor's supervision, but I can't seem to find a decent doctor who knows anything more than prescribing drugs!
So, after dismissing my poor lab results, the doc proceeds to prescribe an SSRI anti-depressant for my poor sleep, and another SSRI for my IBS type symptoms. I'll call tomorrow and tell them I won't take the drugs...I was too caught off-guard to put up an argument today in his office.
Anyhow, the low Alk Phos was interesting, and together with other symptoms I'm strongly thinking I need to up my B6.
My other symptoms pointing to B6 seem to be: the scalp itching/bumpiness (thanks Wikipedia), hair loss, very dry skin (seems to have gotten worse since starting protocol), dry lips (with cracks a few days ago--also new symptom). When I was younger I had angular cheilitis quite often.
And I'm still trying to decide whether to supplement B6 separately, or take the B-complex (probably Swansons ultra).

I agree with Freddd to keep on for now (seeing as I have improvements in other ways), but with caution. When I did back off the folate before, that same day I began to have sore throat and headache, and asthma type symptoms, so I'm worried about lowering dosage.
However, I also agree with Lotus that there is some missing piece which is still unaccounted for in this process. So I will keep a very careful eye. I think titrating up, I'm not going to go over 2,000 mcg of B12, and whatever folate levels associated with that level.
 

Freddd

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has anyone discussed Dr. Nuebranders protocol for b-12 injections ?

He has treated thousands of people with methyl b12 shots and has learned alot of what works and doesnt

http://www.drneubrander.com/Files/READ ME, Injection Instructions for Methyl-B12 Shots.pdf
HI Vortex,

I adapted and adopted Dr Nuebranders protocol for b12 injections and agree with him on most things. I have extended some things, for adults and for those needing the larger CNS penetrating injections, the necessity of foil wrapped syringes and vials to protect the MeCbl, dnsity needs to be 20mg/ml, not 25mg/ml as he suggests becasue a lot of batches won't dissolve fully and then get filtered out in the 0.2 micron filter. So dose volumes need to be adjusted. And frequency of coures, 3x10mg/day subcutaneous is whag I need to maintain brain and cord healing. This active b12 protocol started with Dr Neubrander's protocol more or less circa 2003 and evolved from there. He was a pioneer of so many essential things for injecting MeCbl for best results.
 

xjhuez

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Reasons B12 doesn't work for a person

  • They take active b12 as an oral tablet reducing absorbtion to below 1%. A 1000mcg active b12 oral tablet might bind as much as 10mcg of b12. Again the b12 has to be squeezed through a keyhole that limits the amount and is subject to binding problems in the person whether genetic or acquired.
Is there an accepted explanation or theory for why this is?

From an evolutionary standpoint, that such an important nutrient would be so poorly bio-available via the gut doesn't make much sense.