B-12 - The Shorter Story?

[sensing progress]

I'm interested in learning more about B-12 but don't dare try to read the 1628 (!) posts in the "B-12 - The Hidden Story" thread. Can someone who has been following it give a synoposis of B-12 and how it's significant to those suffering from ME/CFS? I realize it's a lot of material to summarize, but I would like the abbreviated cliff notes version please

 

[cfs since 1998]

I was just wondering the same thing.

 

[JPV]

Most of the important info is in the first few pages of that thread. I will warn you that it isn't presented in the most clearly explained manner. The basics are, more or less, adequately explained, but there are a ton of variables that are scattered on this forum and all over other sites on the Internet. Digesting it all is a serious task, to say the least.

I've been trying it for a few months and have seen modest improvements until having a severe crash last week. Not sure if the crash was from the protocol or something else, but I'm back on it again. It's definitely working as I have more good days than bad, and my brain fog has cleared up significantly. My sweat has become very toxic smelling too, almost frighteningly so, but it gives tangible proof that something is happening.

 

[richvank]

I'm interested in learning more about B-12 but don't dare try to read the 1628 (!) posts in the "B-12 - The Hidden Story" thread. Can someone who has been following it give a synoposis of B-12 and how it's significant to those suffering from ME/CFS? I realize it's a lot of material to summarize, but I would like the abbreviated cliff notes version please

Hi, sensing.

I'll try to give you my perspective on B12 and ME/CFS. I, of course, think it's an accurate perspective, but I must note that there are some differing views on this subject. I'll try to separate hypothesis from what is currently viewed as scientifically established.

First, vitamin B12 is normally used in the human body to form two coenzymes that do different jobs in the biochemistry of each cell. These are adenosylcobalamin and methylcobalamin. Adenosylcobalamin is formed and used in the mitochondria (little power plants) of the cells. It is involved in helping to metabolize certain amino acids and other substances so that they can be used in the Krebs cycle to produce ATP, which powers many of the biochemical reactions in the cells. So adenosylcobalamin is involved directly in energy production.

The more vital form is methylcobalamin. This form of B12 is used as a coenzyme by the enzyme methionine synthase, which is in the methylation cycle. The methylation cycle plays some vital roles in the cells. One is that it makes methyl (CH3) groups, which are needed by a large number of reactions in the cell, some of which make various needed substances, and some of which involve methylating DNA. The latter is important for controlling the expression of genes, and has wide-ranging effects on the overall operation of the cells. The methylation cycle is also located at the beginning of the overall sulfur metabolism in the cells, and thus controls the formation of several other sulfur-containing species, including cysteine, glutathione, taurine, and sulfate. These in turn play important roles in controlling oxidative stress, removing toxins from the cells, and supporting the immune system. So when there is a problem with vitamin B12, it ends up affecting many important functions in the body.

So far, what I've written is considered to be scientifically established. Now I'm going to talk about my hypothesis for ME/CFS. I have hypothesized, that in ME/CFS, as appears to be true in autism as well, there is a partial block of the enzyme methionine synthase, and this partial block is associated with depletion of glutathione in a vicious circle interaction mechanism, which makes ME/CFS a chronic condition. We have lab test evidence that supports this, but it is not yet considered to be scientifically proven by the ME/CFS community.

I have suggested that this situation comes about in most cases of ME/CFS when glutathione becomes depleted as a result of the action of some combination of a variety of physical, chemical, biological and/or psychological/emotional stressors, the combination being different for each case. For a person who is genomically predisposed by having inherited an appropriate combination of polymorphisms, this leads to the partial block of methionine synthase.

I have suggested that the mechanism by which this occurs is that depletion of glutathione removes the normal protection from vitamin B12 in the cells, and also allows buildup of toxins within the cells. The toxins then react with the B12, hijacking it, so that it cannot be used to make the two coenzymes. The results are that the fuel supply to the Krebs cycle is decreased, and more importantly, methionine synthase becomes partially blocked, and the methylation cycle thus becomes dysfunctional, reflecting dysfunction on the rest of the sulfur metabolism, including the synthesis of glutathione, and producing all the symptoms of ME/CFS.

When methionine synthase becomes partially blocked, it also disrupts the folate metabolism, because one form of folate is a reactant of methionine synthase. Since it is not being used by this reaction, it leaks out of the cells into the blood, by a process called the methyl trap mechanism, and this ends up depleting the folate in the cells.

When it comes to treating this condition, there are differences of opinion about how this should be done. I think that all those involved agree that both B12 and folate must be taken simultaneously, but the exact forms and dosages are debated. I have proposed what I have called the Simplified Treatment Approach, so named because it was extracted from the much more comprehensive treatment program developed by Dr. Amy Yasko, mainly for autism, but also used for other neurological diseases as well as for CFS. This treatment uses sublingual hydroxocobalamin as the B12 form, and uses mainly 5-methyl tetrahydrofolate (aka FolaPro, Metafolin, or Deplin) as the folate form, as well as some folinic acid and some ordinary folic acid. There is also a special multi and a phospholipid supplement included.

Most of the long B12 thread to which you referred describes the treatment advocated by freddd for the whole variety of B12 deficiency conditions, as well as for ME/CFS. He recommends relatively large dosages of both methylcobalamin and adenosylcobalamin, as well as 5-methyl tetrahydrofolate and some other supporting nutrients.

There is also the Vinitsky protocol, which uses sublingual hydroxocobalamin together with relatively large dosages of sublingual ordinary folic acid. There are also some additional nutrients used.

The DAN! project for treating autism has used subcutaneously injected methylcobalamin together with oral folinic acid, primarily, and other supplements are also added.

The protocol recommended by Prof. Martin Pall uses hydroxocobalamin and a form of folate also. Initially he recommended folic acid, but more recently seems to be moving to 5-methyl tetrahydrofolate. His rationale for using them is different, being based on his NO-ONOO model for CFS. He believes that the main role of the hydroxocobalamin in CFS treatment is to scavenge nitric oxide, and the role of the 5-methyl tetrahydrofolate is to scavenge peroxynitrite.

I hope this gives you a place to start. It's probably a little more detailed that Cliff notes, but that's about the best I can do!

Best regards,

Rich

 

[Freddd]

I'd like to add some things to what Rich had to say, not to highlight the differences between various protocol forms advocated. It is my opinion that CFS/ME/FMS are all hidden manifestations of various combinations of the 4 specific b12 deficiencies along with some other substances, most frequently methylfolate. Most of the most common b12 deficiency symptoms also include folate deficiency as a possible cause or co-cause, whether the diagnosis is CFS/ME/FMS or some other diagnosis.

THE MOST DANGEROUS SIDE EFFECT OF PRIMARILY THE ACTIVE B12 PROTOCOL

HYPOKALEMIA - In the various references this is mentioned as an anectdotal possiblity with Hycbl and Cycbl. With the methylb12/adenosylb12 this is much more common and can be very dramatic and happen in a major way in just a few days. The form of this with the b12 protocols is a sudden drop in serum potassium. This is generally considered to me just a blood cell formation effect but actually it can be far more widespread. I had at least 4 bouts of it when I had to increase potassium to deal with it; three days after starting mb12, three days after starting adb12 and the same 3 days after starting l-carnitine fumarate, and 4 days after starting methylfolate. With the mb12 I had widespread healing in general but no blood changes. With the adb12 and carnitine I had large sudden changes in muscle healing and growth and with the methylfolate my blood started normalizing and MCV came down.

This appears to occur more often for people with potassium levels under 4.5 when the person starts. I, and others, start having effects around 4.1 to 4.2. Some labs use 3.5 as the low end of normal so some people can have hypokalemic effects well before it gets that low. Also certain diuretics can increase potassium loss. My symptoms are basically severe leg cramps and spasms in a relaxed state such as in bed at night instead of during activity and contractions. They were severe enough that it took me some while to get into the kitchen to get to my potassium. I could not have driven to the store. Others have mood changes and anxiety triggered by this low potasium state. There are a whole range of possible symptoms. This is potentally FATAL if not treated. You don't have time to make a doctor appointment and wait a week or two for the appointment and labs. I've seen people get into trouble not taking this warning seriously. I suggest that a potassium supplemnt always be started immediately, at a modest dose, except for those with high potassium problems. While this is a potentially dangerous side effect it also confirms that rapid healing is occurring.

Two other cautions.

1. Occult tetanus. The mb12 especially can prevent problems with the neurotoxic effects of tetanus making diagnosis difficult. Most docs won't believe it if they don't see the neurotoxic effects, which can be fatal.
2. Botox reversal. Even a 1mg sublingual mb12 may negate the neurotoxic botulism toxin injected in small amounts as Botox for up to 24 hours. Both botulism and tetanus are clostridium anorobic bacteria that produce neurotoxi toxins.

While tetanus is rare because of vaccinations it does happen and I am aware of an actual case. With the botox I am aware of multiple people who had this happen. Methylb12 appears to be the only thing there is that might be able to save a life from botulism poisoning. It has not been tested for this or confimed in any case I know of in humans. Mb12 and Hycbl have been used for years, very successfully, to treat avian botulism and papers exist about that use.

In any of these protocols cofactors can make a critical difference. The ones I have seen that potentially make a night and day type difference are Metafolin, L-carnitine fumarate, SAM-e, B-complex, magnesium, vitamin D, zinc, and smaller but significant differences with TMG, D-ribose and possibly creatine in some people. Often it is a combination of cofactors with the last missing factor added looking like the big one. Some of these are needed for mb12, some for adb12 and some for both. And don't forget the other basics for healthy tissue formation; A, C, E, calcium and others. The effects with Hycbl may be less clearcut in some cases but just as essential for healing. Almost any of these might be a reason for near total lack of effect of b12 in some circumstances.

 

[sensing progress]

Thanks for the responses, guys. I'm afraid at the moment even the abridged versions are too much for my head to wrap around. :worried:

 

[kurt]

Thanks for the responses, guys. I'm afraid at the moment even the abridged versions are too much for my head to wrap around. :worried:

Hi sensing progress,

Just want to chime in that I am also having some success right now with a combined B12 protocol. The combined approach I am using includes both general methylation support as Rich suggests as well as active forms of B12 and nutrient support for healing as Fred suggests . I also add extra B6 support, much more than is found in a standard B complex, as B6 is important in methylation and energy production, and I believe B6 is making the protocol work better. Several other people are following this approach, and I plan to write more details in another post.

If you just want a basic but thorough understanding of B12 and its role in health and disease in general I highly recommend the book "Could it be B12?" by Sally Pacholok & her husband Jeffrey Stuart. They have dealt with some serious B12 problems and I think present a very readable and easy to follow explanation. That book helped me appreciate the importance of B12 and the severity of diseases caused by B12 problems.

 

[zoe.a.m.]

If you just want a basic but thorough understanding of B12 and its role in health and disease in general I highly recommend the book "Could it be B12?" by Sally Pacholok & her husband Jeffrey Stuart. They have dealt with some serious B12 problems and I think present a very readable and easy to follow explanation. That book helped me appreciate the importance of B12 and the severity of diseases caused by B12 problems.

If I'm not mistaken, there is a newer version coming out next year of this book... has anyone else found this? I wanted to order it but got it through my library and am looking forward to an updated version and what it might contain.

This book really should be in every doctor's office; it's shocking that it took me as long as it did to find it!

 

[JamesK]

Thanks for the responses, guys. I'm afraid at the moment even the abridged versions are too much for my head to wrap around. :worried:

I think it's basically the simplified methylation block lifting protocol that we're talking about here.

Someone correct me if I'm wrong.

 

[Freddd]

I think it's basically the simplified methylation block lifting protocol that we're talking about here.

Someone correct me if I'm wrong.

Hi James,

I would have to disagree with your statement. Methylation is only one aspect of what b12 does. It is an important aspect however. For instance, epithelial tissue problems (skin, lungs, digestive system, vaginal, cervix, bladder etc, basically all tissue having contact with the outside world are dependent upon adequate mb12/methylfolate for cell reproduction (part of methylation). Endothelial tissues such as the heart lining, veins and arteries lining and in fact all cell DNA/RNA transactions invlove methylation and are dependent upon mb12/methylfolate. Without adequate mb12 and methylfolate the transactions don't happen or are faulty and/or delayed. This causes elevated CRP and all sorts of lesions and problems from IBS, to cell abnormalities on a PAP test. Homocystein can be elevated but a multitude of problems develop before homocystein reaches a level indicative of a certain level of breakdown in the methylation system. Blood cells of several varieties are all affected by low mb12/methylfolate; white cells, red cells and platelets at the least. This is also because of lack of effective methylation. However, results based on normalizing blood cells can be misleading as methylfolate by itself may correct that without the necessary b12 for the neurology and the blood can respond adequately to very small amounts of hycbl and/or cycbl each 1-3 months whereas that is not adequate for so much else. Immune system functing is also severely impacted without adequate methylb12/methylfolate. As well as not fighting things off as well it can also become hyper reactive apparantly causing or contributing to the cause of a number of autoimmune diseases. Some of this again is methylation related and some may not be.

Then there is the direct effect of mb12 on the nervous system. It affects the nervous system in many ways and can promote healing of neurology in a way not duplicated by any other form of cobalamin. Cell formation activities of course involve methylation but other aspects do not. For instance the cobalamin itself combines with nitrous oxide and some other toxins, disabling the toxins and the mb12. For other toxins such as mercury the methyl group combines with it to make it excretable but also inactivating the mb12.

Adenosylb12, the other active form of b12 has nothing to do with methylation at all. It has everything to do with mitochondrial function. MMA is one indicator of a severe breakdown in mitochondrial function, but again very late in the game after a lot of damage has already occurred. Neurons have mitochndria as well as muscles. Adb12 also is used in some way in the generation of the myelin sheath around the nerves as is mb12. Omega3 oils also are essential for this purpose.


Considering this to be most a methylation block situatuation is not seeing the forest because all the trees are in the way. Methylation block (or depletion as I described it) is a RESULT of methylb12/methylfolate deficiencies, not a cause. It is one of a multitude of results from mb12/adb12/methylfolate deficiencies.

There are separate noticable and definable and overlapping adb12-body deficiency symptoms. There a separate noticable and definable and overlapping mb12-body deficiency symptoms. There are separate noticable and definable and overlapping adb12-brain/cord deficiency symptoms. There are separate noticable and definable and overlapping mb12-brain/cord deficiency symptoms. There are also separate noticable and definable and overlapping methylfolate-body deficiency symptoms and separate noticable and definable and overlapping methylfolate-brain/cord deficiency symptoms.

As studies have shown that people with FMS/CFS/Alzheimer's have a reduced cerebral spinal fluid cobalamin level, in FMS/CFS it is obvious at doses beyond those that make any difference to the body. Researchers have hypothecized that some people have a problem with the system that gets cobalamin into the CSF in the first place requiring large doses according to Japanese researchers. Other researchers have done intrathecal injections of about 5mg of mb12. In these studies CSF cobalamin levels remained effective for functioning and maybe healing for from less than 3 months to more than 1 year. However as healing was not complete by the time it was elliminated from the CSF the neurology reverted to the damaged condition without additional mb12. My own experience and that of many others is that mb12 and adb12 each has it's own specific noticable neurological effects completely separate from body effects.

 

[Freddd]

I'm interested in learning more about B-12 but don't dare try to read the 1628 (!) posts in the "B-12 - The Hidden Story" thread. Can someone who has been following it give a synoposis of B-12 and how it's significant to those suffering from ME/CFS? I realize it's a lot of material to summarize, but I would like the abbreviated cliff notes version please

Hi Sensing progress,

As far as I can tell various combinations of brain mb12, brain adb12, body adb12, body mb12, brain methylfolate and body methylfolate deficiencies are at the heart of ME/FMS/CFS. 100% of the symptoms of these conditions are consistant and/or identical to the 300 or so mb12/adb12/methylfolate deficiency symptoms, signs and co-correlates. Without these substances healing is random. With these substances there is a large probability of significant healing up to and includin essentially 100% recovery. As there are another dozen or so cofactors that can significantly influence how things look, there are thousands of combinations and permutations of the various deficiencies that appear able to account for all the variations seen. Almost 100% of folks with CFS/FMS respond to adb12/mb12/methylfolate and cofactors. How completely and what remains after 1-7 years of the active b12 protocol can tell one what else is wrong. The situations are almost always simpler after dozens to hundreds of symptoms are reduced or elliminated.


While there appears to be many different things that trigger these deficiencies, such as viruses, bacteria and traumatic injury, and this confuses the picture, it is the resulting aftermath that has become chronic with which we are dealing.

Consider what severe chronic pain, CFS, FMS, depression, post polio syndrome, chronic epstein barr, and quite a few other conditions have in common; 80% overlap in symptoms with a very few specific distinguishing symptoms.

 

[kurt]

Hi Everyone,
Just want to share a thought about how to explain this protocol. And I think we really do need a "B12 Protocol for the Brainfogged", maybe the simplest explanation yet. Here is an attempt at that:

B12 is an essential metabolic substance and also a scavenger molecule. There are numerous problems a person can have with B12 metabolism. This is due to the complexity of B12 absorption, transport, activation, recombination, and recycling in the body, as well as the many uses of B12 in the synthesis of other chemicals in the detox/methylation system. Most of the commonly known B12 problems are related to B12 absorption, transport and activation. CFS appears to be a NOVEL type of B12 problem, namely, hijacking of the B12 by rogue neurotoxins in the body. In essence, the B12's scavenger function makes it a target for being kidnapped when there is a drop in protective glutathione levels. And virtually all of the known CFS triggers can be connected to a drop in glutathione levels. So, the CFS trigger leads to depressed Glutathione, which in the genetically vulnerable victims who happen to have a high neurotoxin load leads to a serious loss of B12 in the middle of its metabolism cycle. This creates a complicated failure of multiple chemical reactions, leading to metabolic problems Rich and others have described in some detail. The details for each CFS case will vary based on genetic polymorphisms and ongoing metabolic stress factors.

How to treat this? There are various trains of thought right now, but I find it best to start with the basics. There is one natural form of B12, Hydroxocobalamin, found in some bacteria, and one artificial form, Cyanocobalamin. Both of these can be converted to the active forms used in the body, which are Methylcobalamin and Adenosylcobalamin. Which form of B12 one needs may depend on where in your personal metabolic system the B12 is being 'hijacked' and which polymorphisms you possess. If you are simply desiring to force your metabolism back into working order, the activated forms may be best, as these are guaranteed to help restart some of your internal biological systems that have been shut-down due to B12 starvation.

There is one additional consideration, which is to support the re-start of the various systems and to help recycle the B12. This requires a group of nutrients that are involved in the methylation cycle, as well as other nutrients that may have become depleted during a prolonged period of CFS.

I believe it is both the novelty and complexity of this problem that has led to the disaster of CFS maltreatment by the medical establishment. So what can we do? Fred and Rich and a few others are paving the way for us, and I am having a low-level but significant positive response myself to a B12 therapy that is based on their recommendations. I believe we need to compare notes and continue working this through and discussing our results, until researchers pay attention to this angle of CFS.

 

[Freddd]

The problem is one of diagnosis and definition. Language plays more of a role than the casual observer might realize. "Vitamin B12" is cyancobalamin by definition. Hydroxycobalamin, methylcobalamin and adenosylcobalamin are all, by definition, "b12 analogs" despite mb12 and adb12 being the actual active forms of cobalamin in the body and hydroxyb12 being more active than cycbl. The official "vitamin" is the least active least effective form of the substance that fails to work for 1/3 of subjects in study after study. It is the worst possible choice.

So, when the "vitamin b12" is tested it has some degree of activity in about 2/3 of people. Vitamin C prevents scurvy in 100% of people. Ricketts, beri-beri and pellagra are also prevented 100% in people by the appropriate vitamin.

Are there any other vitamins that works as poorly as cyano b12? Yes, one; folic acid. I and 50% or more of people can take loads of folic acid and still have folate deficiency symptoms curable by other forms of folate. Cycbl and hycbl both only work on about 1/3 of symptoms that respond to adb12/mb12. In other words people can take loads of cycbl and/or hycbl for years and still develop hundreds of symtoms and signs that respond to or respond better to methyb12 and adenosylb12. The reverse is not true.


So, if b12 deficiency is defined as what cycbl can correct without any cofactors the result is a very different one than if b12 deficiency is defined as what a combination of mb12 & adb12 can correct, assuming that the other needed cofactors are supplied. Defining b12 deficiency in terms of test results rather than correctable symptoms appears to miss about 95% of those who would respond to mb12/adb12 including almost everybody with FMS/CFS. Remember, there are no usual tests yet for cerebral spinal fluid cobalamin deficiencies or definitions of what should be considered deficient.

Many countries have quite different lists of symptoms for b12 deficiency. The countries using cycbl defined as the theraputic form have lists drawing from a somewhat different set of symptoms than those using hycbl. Further Japan, the only country investigating mb12 seriously and for longest and most influenced by it has a low alarm level of 550pg/ml instead of 160-170 pg/ml or so as in the USA and UK with muchj more attention to neurological symptoms. They also have an alzheimer's rate of 20% of the USA's.

I prefer to use definitions that produce the highest probability of the most good results. I don't consider it acceptable to treat the body level deficiency problems and ignor the CNS symptoms as untreatable and permanent just to be able to justify the continued use hycbl and cycbl. This treatment based on the inactive cobalamin cycbl was killing me and condemning my children to a life of failing body and neurology. I am affected worse by the combination folate and cobalamin affecting genetics than most people are but it is a matter of degree only. My results are duplicated over and over by people with different causes of deficiency and different genetics. I'm hypersensitive so I see the differences quicker and harder, but they still exist in others.

 

[Freddd]

Hi Everyone,
Just want to share a thought about how to explain this protocol. And I think we really do need a "B12 Protocol for the Brainfogged", maybe the simplest explanation yet. Here is an attempt at that:

B12 is an essential metabolic substance and also a scavenger molecule. There are numerous problems a person can have with B12 metabolism. This is due to the complexity of B12 absorption, transport, activation, recombination, and recycling in the body, as well as the many uses of B12 in the synthesis of other chemicals in the detox/methylation system. Most of the commonly known B12 problems are related to B12 absorption, transport and activation. CFS appears to be a NOVEL type of B12 problem, namely, hijacking of the B12 by rogue neurotoxins in the body. In essence, the B12's scavenger function makes it a target for being kidnapped when there is a drop in protective glutathione levels. And virtually all of the known CFS triggers can be connected to a drop in glutathione levels. So, the CFS trigger leads to depressed Glutathione, which in the genetically vulnerable victims who happen to have a high neurotoxin load leads to a serious loss of B12 in the middle of its metabolism cycle. This creates a complicated failure of multiple chemical reactions, leading to metabolic problems Rich and others have described in some detail. The details for each CFS case will vary based on genetic polymorphisms and ongoing metabolic stress factors.

How to treat this? There are various trains of thought right now, but I find it best to start with the basics. There is one natural form of B12, Hydroxocobalamin, found in some bacteria, and one artificial form, Cyanocobalamin. Both of these can be converted to the active forms used in the body, which are Methylcobalamin and Adenosylcobalamin. Which form of B12 one needs may depend on where in your personal metabolic system the B12 is being 'hijacked' and which polymorphisms you possess. If you are simply desiring to force your metabolism back into working order, the activated forms may be best, as these are guaranteed to help restart some of your internal biological systems that have been shut-down due to B12 starvation.

There is one additional consideration, which is to support the re-start of the various systems and to help recycle the B12. This requires a group of nutrients that are involved in the methylation cycle, as well as other nutrients that may have become depleted during a prolonged period of CFS.

I believe it is both the novelty and complexity of this problem that has led to the disaster of CFS maltreatment by the medical establishment. So what can we do? Fred and Rich and a few others are paving the way for us, and I am having a low-level but significant positive response myself to a B12 therapy that is based on their recommendations. I believe we need to compare notes and continue working this through and discussing our results, until researchers pay attention to this angle of CFS.

Hi Kurt,

There is one natural form of B12, Hydroxocobalamin, found in some bacteria, and one artificial form, Cyanocobalamin

I must disagree with you on this. There are two "natural" forms of b12 which virtually every animal lifeform higher than the bacteria and molds that makes them use right on up through vertabrates and mammels use; adb12 and mb12. There are an additional handful of "natural" forms found in the human body as temporary or post detox forms including but not limited to hydroxycbl, aqueocbl, glutathionylcbl, cyanocbl and probably a few others. In addition there are another dozen or two "natural" plant-active only cobalamins that might be present in small quantities from diets or supplements. As far as I know all of these various forms are made only by various micro-organisms. While cyanocbl was accidently made in the lab from mb12 to win the Nobel prize, cyanocbl is a natural biologically produced form preferred by the kidneys for excretion as it is a post detox excretion form in humans. I know of no artificial forms.

No human uses anything else than adb12 in the mitochondria. No human uses anything other than mb12 for DNA/RNA transcriptions and neurology etc. No matter what form is the intake form, not a mcg is useful until it is converted to either mb12 or adb12.

 

[kurt]

Hi Kurt,

There is one natural form of B12, Hydroxocobalamin, found in some bacteria, and one artificial form, Cyanocobalamin

I must disagree with you on this. There are two "natural" forms of b12 which virtually every animal lifeform higher than the bacteria and molds that makes them use right on up through vertabrates and mammels use; adb12 and mb12.

I was only talking about non-activated forms in that sentence, and mentioned the activated forms later. But of course the activated forms are also natural. Probably that should be more clear, this is just a first attempt at a simplified explanation.

On this same topic, another problem with people taking either Hydroxo or Cyano form is that both require a healthy liver and nutrient co-factors, for conversion to adb12 and mb12 to take place. Ever met a CFS patient with a healthy liver and good nutrient status?

 

[richvank]

I was only talking about non-activated forms in that sentence, and mentioned the activated forms later. But of course the activated forms are also natural. Probably that should be more clear, this is just a first attempt at a simplified explanation.

On this same topic, another problem with people taking either Hydroxo or Cyano form is that both require a healthy liver and nutrient co-factors, for conversion to adb12 and mb12 to take place. Ever met a CFS patient with a healthy liver and good nutrient status?

Hi, Kurt.

A healthy liver and good nutrient status are certainly important, but as I understand it, the conversion to methylcobalamin and adenosylcobalamin normally takes place in all the cells individually, not just in the liver.

Best regards,

Rich

 

[Wayne]

A healthy liver and good nutrient status are certainly important, but as I understand it, the conversion to methylcobalamin and adenosylcobalamin normally takes place in all the cells individually, not just in the liver.

Best regards, Rich

Hi Rich,

I've long wondered where glutathione is made. Would that be in individual cells as well?

Thanks to you, Fredd and Kurt for all your input on this thread. I too had despaired of ever sorting through the immensely long B-12 thread, and simply gave up. This thread feels like an opportunity to start anew. I hope I can keep up this time around. :worried:

Wayne

 

[richvank]

Hi Rich,

I've long wondered where glutathione is made. Would that be in individual cells as well?

Thanks to you, Fredd and Kurt for all your input on this thread. I too had despaired of ever sorting through the immensely long B-12 thread, and simply gave up. This thread feels like an opportunity to start anew. I hope I can keep up this time around. :worried:

Wayne

Hi, Wayne.

The liver is the main producer of glutathione in the body. It uses some, and exports some to the bile and some to the bloodstream. The red blood cells are net producers and exporters of glutathione, also. But I think most cell types have the capability to produce it to some degree. Those that have a complete transsulfuration pathway, so that they can convert methionine to cysteine, which is usually the rate-limiting amino acid for making glutathione, are in the best position to make glutathione when cysteine becomes scarce. The organs whose cells have a complete transsulfuration pathway are the liver, kidneys, pancreas, intestine, lens of the eye, and to a much smaller extent, cells in the brain.

Best regards,

Rich

 

[kurt]

Hi, Kurt.

A healthy liver and good nutrient status are certainly important, but as I understand it, the conversion to methylcobalamin and adenosylcobalamin normally takes place in all the cells individually, not just in the liver.

Best regards,

Rich

Do you mean all cells in the body? My understanding is that the liver converts and stores more B12 than any other system in the body, about half of the total. So it seems fair to say that B12 conversion will be more problematic when liver health is poor. And most CFS patients have functional liver detox impairments, phase I and phase II imbalances, often quite severe. I don't know exactly how that might alter B12 conversion, but certainly the resulting free radical problems suggest some wasting of B12 by the liver.

This is a little tangental, but I also recall reading somewhere that folate metabolism takes place primarily in the liver. So the liver seems like a major player in the B12 wasting/depletion theory of CFS.

 

[Freddd]

Do you mean all cells in the body? My understanding is that the liver converts and stores more B12 than any other system in the body, about half of the total. So it seems fair to say that B12 conversion will be more problematic when liver health is poor. And most CFS patients have functional liver detox impairments, phase I and phase II imbalances, often quite severe. I don't know exactly how that might alter B12 conversion, but certainly the resulting free radical problems suggest some wasting of B12 by the liver.

This is a little tangental, but I also recall reading somewhere that folate metabolism takes place primarily in the liver. So the liver seems like a major player in the B12 wasting/depletion theory of CFS.

Hi Kurt,

Do you mean all cells in the body?


I'm sure he does. This conversion from one form to another happens with various specific enzymes at the cell level. Some people lack or have reduced amounts of any of the various required enzymes, which is a condition that I appear to have. As the average person has in the body about 2.5mgs (some sources say as high as 5mgs, but I can find no source that specifies by tissue type contents of b12 that adds up to anything near that high. Half of that is said to be stored in the liver awaiting disposal through the bile. This is how the body "refines" the cobalamins, getting rid of the mix of non-active and active cobalamins and then reabsorbing the active ones so excreted at near 100%. The blood has approximately 2-6 mcgs circulating cobalamin (serum level - 200-1200pg/ml), mostly methylb12 according to many researchers. All the rest is in tissues in varying concentrations. Then, it's supposed to be converted to adb12 if needed but everything else uses mb12. If it is in other forms ie hycbl, cycbl, glutcbl then it must be converted. Since only limited amounts can be converted if a person needs more, too bad. If a person can't convert for genetic lack of the needed enzyme, so sad too bad send flowers to the funeral.

The advantage of taking the sublingual active b12s; mb12 and adb12 directly is that the entire complicated system of assumption based on assumptions is bypassed.

ASSUMPTIONS BYPASSED by SUBLINGUAL ACTIVE B12S

1. A person has a fully functional unbypassed digestive system and Intrinsic Factor eating meat, fish, eggs and low b12 content milk.
2. A person has a functional transport system and sufficient methylfolate (NOT folic acid for at least half the people)
3. A person has all the enzymes needed for interconversion from inactive forms to active forms and for converting one active form to another.
4. A person can utilize no more B12 than the transport system can handle, about 6mcg per day. This transport system can be entirely saturated by cyanocbl at doses of 50-100mcg per day according to research, which indicates that cyanocbl demonstrates dose proportionaly in binding to transport system over the range of 1 to 50-100mcg.

Sublinguals put the active b12s requiring no conversion into serum making it directly available to all tissues by diffusion bypassing the most complicated system for any vitamin which can go wrong in any of hundreds of details.

Methylb12 has demonstrated dose proportionality over the range 10mcg to 30,000-50,000 mcg per day. This may partly be demonstrating better tissue penetration, especially brain and cord, by diffusion at higher doses. However, the sudden availablity to almost every cell in the body all at once to both kinds of active b12 they need not limited by absorption, transport and conversion keyholes, can produce sudden onset startup responses.

When one has plenty of serum mb12 and adb12 wastage doesn't matter as most will be excreted anyway. Mb12 and adb12 are both disabled and excreted after they have performed their detox functions, such as combining with cyanide and removing it from the body. Both SAM-e and methylb12 help detox the liver.