B-12 - The Hidden Story

[Dreambirdie]

Thank you Rich. I always appreciate your posts about this.

I haven't yet begun the Simplified Protocol, but will be headed in that direction, once I regain some stability. It's helpful to gather as much info about it before I decide to take that plunge, and you have a wealth of that.

One Question, WHAT IS THE NAME OF THE LAB TEST for DETOX PHASES?
the one that test the Phase 1, Phase 2 ... I keep forgetting to write it down.

 

[richvank]

I took various forms of sublinguals for many months, using both "active forms" and did all sorts of things like keeping them in my mouth for nearly an hour as they slowly dissolved and taking many grams of them per day using all the "right" brands...never felt any different. Hydro injections have made a world of difference and my blood counts finally improved once I switched to them...if it works, stick with it I say.

Hi, Big and Cloud.

I'm glad to hear that you have experienced benefit from hydroxocobalamin injections. Though I favor this form of B12 for the treatment of CFS, I am surprised that the other forms did not help you, also, since the cells can normally utilize any of the forms of B12 and convert them to what they need. This makes me wonder whether your cells might have a problem in removing the alkyl ligands (methyl and adenosyl) and maybe the cyano ligand, also. There is a particular gene product that normally carries out this removal, but mutations in it are thought to be fairly rare. So I'm a little puzzled by this, but glad the hydroxo B12 is working for you both.

Rich

 

[richvank]

Thank you Rich. I always appreciate your posts about this.

I haven't yet begun the Simplified Protocol, but will be headed in that direction, once I regain some stability. It's helpful to gather as much info about it before I decide to take that plunge, and you have a wealth of that.

One Question, WHAT IS THE NAME OF THE LAB TEST for DETOX PHASES?
the one that test the Phase 1, Phase 2 ... I keep forgetting to write it down.

Hi, Dreambirdie.

It's called the Comprehensive Detoxification Profile. It's offered by Genova Diagnostics. It can be found here: http://www.genovadiagnostics.com/files/profile_assets/further_information/detox-1pager.pdf

Best regards,

Rich

 

[Dreambirdie]

Thanks Rich!

 

[Sunday]

Dreambirdie, good luck. I'll be looking for you on the methylation train.

Cloud, it's possible that your lack of response to methylcobalamin has to do with the brands you chose to try. Freddd has done some surveys on brands and there are only a couple that seem to work for most people. This isn't necessarily a reflection on the brand; there's at least one company whose quality is really good, but their SLmb12 doesn't seem to work well for most of us.

You are probably responding more to the hydroxycobalamin because cyanocobalamin is pretty close to totally inactive until our bodies convert it - if they are able to. Some of us could never make the conversion; others (like myself) no longer can. You might want to read the first 3 pages of this thread, where Freddd lays out his understanding of the different types of vitamin b12 and the dosages your body actually receives, as opposed to the dosage on the syringe or bottle. He believes the sublinguals he recommends are actually more effective than hydroxycobalamin injections. Rich thinks differently, or at least that's how I read it. I think we're actually lucky to be a part of Freddd and Rich's debates and the experiments around them; different perspectives allow us to see further, and with more depth.

 

[Freddd]

Dreambirdie, good luck. I'll be looking for you on the methylation train.

Cloud, it's possible that your lack of response to methylcobalamin has to do with the brands you chose to try. Freddd has done some surveys on brands and there are only a couple that seem to work for most people. This isn't necessarily a reflection on the brand; there's at least one company whose quality is really good, but their SLmb12 doesn't seem to work well for most of us.

You are probably responding more to the hydroxycobalamin because cyanocobalamin is pretty close to totally inactive until our bodies convert it - if they are able to. Some of us could never make the conversion; others (like myself) no longer can. You might want to read the first 3 pages of this thread, where Freddd lays out his understanding of the different types of vitamin b12 and the dosages your body actually receives, as opposed to the dosage on the syringe or bottle. He believes the sublinguals he recommends are actually more effective than hydroxycobalamin injections. Rich thinks differently, or at least that's how I read it. I think we're actually lucky to be a part of Freddd and Rich's debates and the experiments around them; different perspectives allow us to see further, and with more depth.

Hi Cloud, dreambirdie et al,

I think it's a good time to go over a few basics of what I did, and did not do, and what is conjecture versus results just to clarify things. I admit that sometimes I get frustrated that I have trouble communicating what I see so clearly see, but that is a probelm I have had for a long time. I sometimes take logical shortcuts that others don't follow.


I and 4 other hypersensitives to active b12s did comparative testing of 10 brands of sublingual methylb12.

Jarrow 5mg and 1mg and Enzynamatic Therapy 1mg came out as 5 stars, superior and able to make a difference over all other brands and no other brands were able to have a differential effect over them. Reporting only the unanamous results, those two were equal. In my experience, unduplicated by the other 4 , the Enzymatic Therapy was very slightly better. During the first year of most rapid healing I took both brands daily just to be sure. Country Life Dibencozide, the only sublingual adenosylb12 tested was fully equal to the 5 star brands of mb12 judging purely on it's dramatic effectiveness by all 5 testers. No other brands of methylb12 exceeded 1.5 stars when considering the size of the performance differences. One brand was ZERO stars, totally indetectable by all 5 testers allowing full and rapid return of all symptoms.

As I inject methylb12, with my doctor's cooperation I did a series of injections titrating for effect. I found that 1-6mg per subcutaneous injection were all about the same except for urine coloration. At 7.5mg something different happened and there was a dramatic central nervous system effect. From 7.5mg to 25mg SC in a single injection there was no additional difference except for urine color. Others have duplicated this.

Furthermore adenosylb12 and methylb12 each had their own specific effectiveness at the 7.5mg dosage. Others have duplicated this.

In adjusting frequency I found that 4x7.5mg sc daily or 3x10mg sc daily maintained maximum CNS effectiveness in causing healing of CNS damage. Others have duplicate this and some have found that 2x15mg works as well for them.

In another series of tests in calibrating subligual absorbtion under lip and/or tongue, 45-120 minutes of tissue contact of 50/51mg of sublingual tablets as a single dose produced the same CNS effectiveness and urine coloration as 7.5mg - 12.5mg injection. This corresponded with 15-25% absorbtion of the sublingual in 45-120 minutes.

For ME. due to the hypothecized rare genetic condition, I find cycbl and hycbl virtually totally ineffective. It only takes a few minutes of light exposure of injectable methylb12 to change enough of it to hycbl that it gives me acne type lesions and allows neurological deterioration to resume reversing previously made gains. Other people have duplicated this. This happens in way too many people to account for it via some hypothetical rare genetic cause

In another situation I recruited persons who were sensitive to b12 but not hypersensitives. They were never tested on any but 5 star methylb12 and adenosylb12 or both. They did no comparitive testing of brands. I gave them free bottles of b12, when needed, which they took for a month and then we tried challange doses of the other variety. There was no control over whether they took cofactors or anything else of the sort. It was done very early in learning about these things and needs to be redone properly.

In dozens of people tested, those having separate responses to methylb12 and to adenosylb12 after equilibrium is reached on the other methylb12 or adenosylb12, in almost 100%. This happens in way too many people, almost everybody, to account for it via some hypothetical rare genetic cause.

In dozens of people tested those trying methylb12 had a differentential effect over hycbl after reaching equilibrium on hycbl, in almost 100%. This happens in way too many people, almost everybody, to account for it via some hypothetical rare genetic cause

In dozens of people tested those trying adenosylb12 had a differentential effect over hycbl after reaching equilibrium on hycbl, in almost 100%. This happens in way too many people, almost everybody, to account for it via some hypothetical rare genetic cause

In dozens of people tested those trying methylb12 had a differentential effect over cycbl after reaching equilibrium on cycbl, in almost 100%. This happens in way too many people, almost everybody, to account for it via some hypothetical rare genetic cause

In dozens of people tested those trying adenosylb12 had a differentential effect over cycbl after reaching equilibrium on cycbl, in almost 100%. This happens in way too many people, almost everybody, to account for it via some hypothetical rare genetic cause

In dozens of people tested those trying cycbl had a differentential effect over methylb12 after reaching equilibrium on methylb12, in 0%. This happens in way too many people, almost everybody, to account for it via some hypothetical rare genetic cause

In dozens of people tested those trying cycbl had a differentential effect over adenosylb12 after reaching equilibrium on adenosylb12, in 0%. This happens in way too many people, almost everybody, to account for it via some hypothetical rare genetic cause

Obviously there is one set not yet tested, looking for differential effectiveness of hycbl over equilibrium mb12 and adb12.

My testers were pretty sick of me and all the setbacks they kept having after trying these other things. They went on strike. I was sick of the setbacks too and out of money. At this point we just set out to elliminate setbacks and keep healing continuous which has not been nearly as easy as it might seem.

I am making the best progress I have ever made on reversing the numbness in my feet the past few months and have had no setbacks in that time for the first time ever. I am controling light exposure all along the course of the mb12 including the draw into the syringes and I am taking oral Metafolin with each injection. Each little increment of improve,ment has made a difference.

Of those who have tried suprathreshold doses of 7.5mg-15mg (50/51mg sublingual), not everybody finds a difference.

Those that do find that it makes a difference in things, find that is is generally in damage that they have generally been told to expect to be "permanent".


In ALL of these various things with all forms of b12, cofactors such as Metafolin can make a huge difference in overall perfomance.

 

[Big]

Fredd, I respect all the information you've provided and appreciate the fact that you've improved your life dramatically following your protocol. All the information you provided though has led myself and others who've tried the brands you've specified and the techniques you've specified to come to the conclusion that something was wrong with us, or the way we were doing things, or the brands we were using when that was not the case. If I had just had hydro injections right off the bat as my doc suggested I would have made a heck of a lot more progress.

Your methods are based on what you've experienced and that means they are valid for you and certainly others as well so it's good you share them. When you start to talk of "5 star brands" (as decided by you) and "sensitives" and "hypersensitives" (again, 2 groups that were decided by you and thus named) and talk about "cns effectiveness" (as decided by you) it makes this stuff so esoteric and uniquely yours that when others try these methods and don't experience the same benefits you seem to infer that there is something wrong. I could just as easily gather a group of people who benefited from hydro injections and subgroup them by the responses they had and the brands of injections they used.

I frankly don't know enough, nor have I researched this enough to make sweeping statements about either method. What I do know is that I came across your posts many months ago on this forum and others and followed your techinques with no result and much discouragement. I literally felt much better the very first day I took a hydro injection.

 

[Freddd]

Fredd, I respect all the information you've provided and appreciate the fact that you've improved your life dramatically following your protocol. All the information you provided though has led myself and others who've tried the brands you've specified and the techniques you've specified to come to the conclusion that something was wrong with us, or the way we were doing things, or the brands we were using when that was not the case. If I had just had hydro injections right off the bat as my doc suggested I would have made a heck of a lot more progress.

Your methods are based on what you've experienced and that means they are valid for you and certainly others as well so it's good you share them. When you start to talk of "5 star brands" (as decided by you) and "sensitives" and "hypersensitives" (again, 2 groups that were decided by you and thus named) and talk about "cns effectiveness" (as decided by you) it makes this stuff so esoteric and uniquely yours that when others try these methods and don't experience the same benefits you seem to infer that there is something wrong. I could just as easily gather a group of people who benefited from hydro injections and subgroup them by the responses they had and the brands of injections they used.


I frankly don't know enough, nor have I researched this enough to make sweeping statements about either method. What I do know is that I came across your posts many months ago on this forum and others and followed your techinques with no result and much discouragement. I literally felt much better the very first day I took a hydro injection.

Hi Big,


It is certainly important to notice diffferences. Elsewhere there is a forum full of people who have found this inforation most helpful as most of them had already found the hycbl and/or cycbl quite ineffective, far more of them than could be accounted for by any rare genetic variations. I would very much like to see some fully controled tests done so we can actually pin down all the variables invloved. The research done to date is terribly inadequate and almost killed me and certainly hindered the life and health of many people. Differences can appear for all sorts of seemingly trivial reasons, and I say seemingly, becasue they are huge to those affected but might seem like little things, like the pH of the mouth for instance in the case of rthe sublingual. We, those of use that did participate did find huge differences from brand to brand, and we speculated as to all sorts of casues. As we all responsed simerlaly across the various brands it did appear to be brand related as opposed to individual variations but in a small N trial, there is no way to no for sure. As all the brands and all the items were completely new to all of us nobody had any expectations at all. We were just trying to figure out why there were such huge differences between brands that were were all aware of. If you were to gather a group together to do your own series of testing and whatever results you came up with, that would be excellent. Repeatability, or not, is an important test in and of itself.

When one does a wine tasting for instance, one attempts to select persons who have the innate ability to sense subtle differences between several wines. In a chili cookoff one wants to use people who can taste the differences in chili. I would make a lousy judge for chili comparisons for instance. If you choose somebody who can't smell or taste the difference the results are going to mean nothing at all. If one at least chooses a person who can sense differences on which to make a distinction, maybe the distinctions will be meaningful. So in choosing a "sensitive", I selected persons who could tell that there was a difference. This was different from hypersensitives by degree; the hypersensitives being far more sensitive to far smaller differences. It was all a relative and comparitive difference. The hypersensitives selected themselves.

As a lot of people, not all of them, but a lot of them, have repeated our results quite often certain things have turned up repeatedly for instance. It is most frequently people taking the active b12s and active folate that find that glutathione (precursors) disable the active b12s and folate. Those taking hycbl don't necessarily have the same results with glutathione (precursors). Why is that? I have no idea. We have way to few people with results tpo give any idea.

So why you had the results you had is quite unknown to me and with the dearth of information given, not likely to be known. As there is a reason for everything, I'm sure it would aid understanding all the way around if that could be pinnded down exactly. At the moment it's all a crap shoot. All anybody can do is try to increase the odds a bit in their favor by controling as many of the factors as they can that might make a difference. For an awful lot of people, what brand used does make a difference but exactly why is not known.

So if you don't like the selection of hypersensitive testers I used, go round up some who respond like you, give them some vitamins and make some tests. Maybe then we would have enough info to say "Eureka" and jump from the batth and run excitedly down the street as did Archemedes.


I could just as easily gather a group of people who benefited from hydro injections and subgroup them by the responses they had and the brands of injections they used.

That would be very useful. What if you found that one brand was tremendously more useful and another didn't work for anybody and you had everybody try every brand you might pin down something that makes a difference for a lot of people. I strongly encourage you to do just that. Maybe the answer is that you have trouble absorbing all brands subligually and that ONLY injections are going to work for you. You wouldn't be the first person for whom that turned out to be the case. Some people just have to have injections. Lack of sufficient information prevents us from knowing why. So a series of injection trials by you might be very informative.


It is my desire to be able to pin down as many variables as possible so that each person could fill out a profile with all their reactions and responses to as many things as possible to help them pick out the things with the best probablity of working based on their individual profile. I know that seems like a long shot but that is what my aim is.

 

[doveman]

Hi RichVank

I thought I'd share my experiences with hydroxycobalamin injections and methyl/adenosylcobalamin sublinguals (taken with Methylfolate and B-Right) in case you find them interesting or you can make any observations.

I've suffered from numerous health problems for years, including fatigue, depression and gut issues (including gluten and lactose intolerance). I started taking a PPI for gastritis in 2006 and some time after that developed pain in my left shoulder/upper back, and also parathesia and burning aches in my ankles. After reading an article linking PPI use to B12 deficiency, I got my serum B12 checked in July 2009 and it was 141ng/L.

I then had 5 "loading" injections of hydroxycobalamin and the shoulder pain, parathesia and burning ankles were relieved, but the shoulder pain returned about a week after the last injection and was not relieved again by monthly injections. My B12 level was checked on the day of the 5th injection (just before it) and it was 1516ng/L.

I then decided to try taking B-Right (1*day), Methylfolate (1 or 2/day) for a week and then adding one Jarrow Methylcobalamin 5000mg sublingual/day (held in mouth for 45-60mins). This did nothing for the shoulder pain, but did result in me feeling refreshed after 6 hours sleep, whereas normally I struggle to drag myself out of bed after any amount of sleep. This persisted whilst I continued taking the Methylcobalamin.

I then added one Country Life Dibencozide 3000 mcg sublingual/day (also held in mouth for 45-60mins) and the morning after taking this for the first time, I felt extremely happy, more so than I can remember feeling since I was a young boy. Unfortunately, this didn't re-occur on subsequent days.

It may be that if I'd been taking B-Right and Methylfolate when I was having the hydroxycobalamin injections, the effects would have been similar to the sublinguals, but I'm unlikely to be able to get my doctor to provide every other day injections again so I'm unable to test that theory.

I had my last hydroxycobalamin injection just before Christmas and haven't used the sublinguals since then. I also stopped the PPIs as my gastritis had settled down. My B12 level was checked on 11th March and it was 512ng/L. I started taking the PPIs again on that date as my gastritis has flared up again. I also found out I was Vitamin D deficient around then (21mmol/L) and judging by my pain probably have osteomalacia, so I'm taking 5000IU/day of D3 to treat that. The D3 has relieved my shoulder pain about as much as the hydroxycobalamin injections did, so perhaps they just allowed my body to better utilise the limited Vitamin D I had.

I finally got to see a haemotologist a couple of days ago and she's taken blood to check my MMA (amongst other things judging by the number of vials taken!) and wants me to return in 3 months, during which she wants me not to take any B12, so that she can check it again. I'm not clear what this is meant to achieve (guess I should've asked!) but my ankles are starting to burn/ache again, so it's going to be hard to resist taking the sublinguals knowing that they'll probably relieve the discomfort. I think she's also referring me to a neurologist and a psychologist to investigate my cognitive and other (possible) neurological problems

I should also mention that I've tried many SSRIs over the years for depression and all they've ever done is make me extremely fatigued, to the extent that I could do little more than sleep on the sofa all day. One of them, Seroxat, made me so irritable that I felt I was a danger to myself and others, so I stopped that abruptly (rather unwisely I've since realised), which caused various complications, some of which seem to have persisted several years later.

 

[Freddd]

Hi Big,

One other thing that I don't mention oftern enough. I suggesrt that people always try at least 3 different variations of things; different forms, different brands different timing, different variations, all that. It's important. The object was to get people off to a start of some kind and then improve and fine tune from there, always looking for that next increment of improvement. I tried to save them from as many bad choices as I could but that is always relative. My internist says it's "too complicated". That is why Rich has a "simplified" form. The full form is complex and yet that is where the best performance comes from. Good luck.

 

[nicola]

CFS vs B12 deficiency - Rich

Hi, freddd.

It really would be good to be able to compare the various protocols on the same basis to see which works the best in CFS. However, I think that in order to do this, we need to make sure that we are dealing with cohorts that are representative of the CFS population.

I understand that there has been considerable success with your protocol, but I continue to wonder how many of the people who have had this success would meet the Fukuda et al. or the Canadian case definitions for CFS. I note that a great deal of the experience with your protocol has been had by people on the B12 deficiency thread of the wrongdiagnosis forum.

I want to reiterate that I do not believe that B12 deficiency is synonymous with CFS. There are many subgroups of B12 deficient people, and I can understand how your protocol would be almost universal for them, because it bypasses the normal absorption, transport and processing of B12, so that whatever problems people might have in those areas, your protocol would leapfrog over them. I think that's wonderful, and I'm glad that your protocol has been able to help these people.

However, as you know, the focus here is CFS, and I think it is necessary to make sure we are talking about people with CFS when we make comparisons of the outcomes of different protocols for the treatment of CFS. So I'm sorry, but I just can't accept your conclusions unless you can show that your cohort actually represents people who have CFS. You may be correct in your conclusions, and I would like to know if you are, but I don't think your argument satisfies the requirements that would make it valid.

One other thing: You've suggested that treatment with the protocol that uses hydroxocobalamin does not help with the neurological or brain-related issues in CFS. However, in our clinical study of people who did meet the Fukuda criteria for CFS, we found that they reported a significant increase in "mental clarity," which I take to mean that this protocol did help their brain function.

Best regards,

Rich

Hi Rich

could you clarify in which way B12 deficiency differs from CFS? I agree with you, and think it may be why so many CFSers experience detox, which is long and difficult rather than a short-lived start-up.

thanks

Nicola

 

[Freddd]

Hi Rich

could you clarify in which way B12 deficiency differs from CFS? I agree with you, and think it may be why so many CFSers experience detox, which is long and difficult rather than a short-lived start-up.

thanks

Nicola

Hi Nicola,

I was going to take a shot at this also. It is really rather more complicated than the simpleness of the question. Part of the problem is in the language itself. First I would lke to define my experience aver a lifetime.

From early childhood until late 20s I had, lets call it X1 for convieninence. I was sick a lot. I had delayed speech as a chid diagnosed as delayed myelination. I was diagnosed hypothyroid at 8 years old. Taking thyroid extract made no difference at all that I could tell but the docs were happy with it. At 24 I was broken in half sideways when a truck ran a red light. A few years later I developed a clear cut case of Fibromyalgia, lets call it X2. That's not unusual, lots of folks develop FMS in a few years following traumatic injury. Only problem was they didn't have such a diagnosis then and I was treated badly then in line with the manner of the times. Approximately 10 years later I had a severe flu like viral illness, along with my wife and a lot of people in the area. She recovered in 6 months. I didn't. I had zero energy and all the usual symptoms of Chronic Fatigue Syndrome and there I sat for 16 years. Let's call that X3. Along the way I developed a whole lot more symptoms than fit into the CFS/FMS pure definitions that were later devloped. I included all the symptoms required for the diagnosis and was eventually given such, several times. It's just that I had a lot more wrong as well which was chalked up to the traumatic injury and other things., including still "I't All In Your head" since I had "too many symptoms to be believable" according to one doc.


The injuries from the car accident caused so much more problem than you might believe. They obscurred everything. All the docs wanted to call it "Chronic Pain Syndrome" etc. What it amounted to was no effective treartment at any time for decades and the various docs playing "blame the patient" with "It's All In Your Head". This is something just about everybody here has been through, being badly treated by the docs and blamed for our illnesses.

It was complicated enough not a single doc of any of the many specialties I went to see had any real idea of how to treat it. I received lots of treatments of many sorts and paid and paid and paid and nothing did any good.

There is a lot of detail I left out here, including a period of being a vegetarian which was likely one of the worst choices I ever made. However, everything put together viewed over a lifetime, coupled with a series of responses to what eventually worked, has allowed me to reasonably define the 4 main variations of b12 deficiencies. These are complicated additional things like inability to convert folic acid to active folates, very common in the CFS/FMS group.

It's no accident that the methylation reactions or lack thereof are such prominent players in this whole things as that is central to our body funtioning. However dividing up the effects by body system afflicted doesn't work for this. So a gastroenterologist, cardiologist and the dermatologist are seeing three different manifestations of the same tissue breakdowns caused by the inability to complete the methylation cycle. And we can add in the specialists involved with all the other tissue breakdowns still casued by lack of methylation. The problem still isn't solved that way. Each specialist misses the boat and treats us in a way that isn't the real solution. Viagra is helpful but it doesn't get at the root of the endothelial tissue dysfunction in the first place.

Rich, with his focus on the methylation breakdown is on the right path because this is at the root of so many different problems. The methylation breakdown however is not the root of the problem but rather the result of even deeper causes.

So in one respect the destruction of my life by so many seemingly inept specialists and decades of lousy treatment that didn't work was a lousy deal, it really sucks. However, it also gives me a lot of data and insight into how they were thinking and where they were going wrong. It clearly points out the institutional therapy and research based blind spot in which I exist, which was going to kill me if I didn't do something about it.

Then in addition to the 4 main groupings, the 8 secondary from ability to convert folic acid or not and a lot of other subgroupings based on other things being present or not present, we end up with a tree like structure such as a "tree of life" representation, with the various named and unnamed disease states branching off in various ways and combinations.

So for instance, a moderate CNS/CSF methylb12 deficiency coupled with a moderately severe body wide adenosylb12 deficiency and mild body methylb12 deficiency with inability to convert folic acid comes up with something that might look an awful lot like CFS/FMS.

I'm not sure of all the details here, so I'm still working on it. Every bit of information people contribute is helpful. The trick is understanding it and seeing how it fits into the overall structure.

Without using the same protocol in comparing length of startup for condition A1 versus condition A2 it becomes an impossible question to answer.

I see plenty of people with CFS/FMS, including myself, have a relatively short (3 month) and intense startup period. Others have longer or shorter, more or less intense startups with similar protocols and very pronounced differences with different protocols.

CFS appears to be a small subset of the much larger set of symptoms that includes all of b12 deficiency. What limits it to that particular subset of symptoms? What makes some people with CFS sicker than others with CFS? What causal factors make it differ from FMS? What causal factors distinguish it from ME? Don't confuse labels with actualities.

What changes that allows somebody having an awful time of it round the corner and suddenly be doing a lot better such as Winston (Lena) has recently reported elsewhere? If we knew the answer to that perhaps it could be made a lot easier for many people.

 

[richvank]

Hi Rich

could you clarify in which way B12 deficiency differs from CFS? I agree with you, and think it may be why so many CFSers experience detox, which is long and difficult rather than a short-lived start-up.

thanks

Nicola QUOTE]


Hi, Nicola.

Please note that I said that I don't "believe" B12 deficiency is synonymous with CFS, not that I have proven it (yet!)

With that understanding, I'll tell you what I think at this point, based on the available evidence of which I'm aware.

I believe that the the hallmark of CFS (and of autism, which I believe is the same disorder, the obvious differences being due to the earlier age of onset) is a chronic vicious circle mechanism that includes a partial block of the enzyme methionine synthase in the methylation cycle, draining of folate metabolites from the cells, and depletion of glutathione.

I also believe that this disorder usually begins with depletion of glutathione by any combination of a variety of physical, chemical, biological and/or psychological/emotional stressors, and in order for it to develop in an individual, there must usually be a genomic predisposition toward development of this vicious circle.

Vitamin B12 deficiency, as freddd alluded to, is a heterogeneous disorder.

Its most common cause is a malabsorption disorder, which can have a variety of causes, including celiac disease, Crohn's disease, or surgeries that have removed the latter part of the small intestine.

The second most common cause is pernicious anemia, which is an autoimmune disorder that destroys the cells in the stomach that produce intrinsic factor, and which is often genetically related.

Low intake of vitamin B12 is another frequent cause, particularly in vegetarians and especially vegans.

Extensive exposure to nitrous oxide anesthesia in dental procedures or surgery oxidizes B12, and can be a cause of B12 deficiency.

Drugs such as proton pump inhibitors, histamine H2 receptor blockers, metformin, and Questran can deplete B12.

Just getting older is also a factor, because the stomach lining tends to degrade as we get older, producing less stomach acid, which is necessary to free B12 from protein in our food, so that it can be absorbed.

There are also inherited genetic issues, such as a deficiency of transcobalamin or inborn errors of metabolism in the intracellular cobalamin-processing enzymes, such as the one freddd has.


If a person has the genetic predisposition toward developing CFS, I believe that the above processes can also be a cause of CFS for that person, as can anything that interferes with they body getting enough folate.
I believe that it is possible to have both B12 deficiency and CFS in such cases, though I suspect that the formal case definitions for CFS would rule this out on the basis that the exclusionary diagnosis requires that other known medical causes for the symptoms must be ruled out before CFS can be diagnosed.

But in my mind, the crucial aspect for defining a case of CFS is that vicious circle mechanism, which is what I believe makes CFS chronic.

Many of the cases of B12 deficiency can be corrected by giving vitamin B12 in a way that it can reach the cells. Conventional doctors do this by injection of cyanocobalamin or hydroxocobalamin, and that corrects most of the cases. I realize that it does not correct cases such as freddd's, because the problem in those cases is inside the cells themselves, not in the absorption into the body or the transport of B12 to the cells.

CFS, on the other hand, cannot be corrected by providing B12 alone, even in large dosages, as was pioneered by Paul Cheney and Charles Lapp several years ago, though it does help to relieve symptoms temporarily.
In order to break the vicious circle, enough folate must also be given, and the chemically reduced forms are best.

I suspect that this stable vicious circle mechanism is not present in most cases of B12 deficiency. If it were, I don't believe that just injecting B12 would correct this disorder.

I would love to see some methylation pathways panel results on people who have ordinary B12 deficiency to test out this hypothesis. It would also be interesting to see such results on people who have the type of inborn errors of metabolism that freddd has, but I would not put them in the same cohort with the other B12 deficiencies that involve low intake, malabsorption, pernicious anemia, transcobalamin deficiency, drugs, or the other causes.

Best regards,

Rich

 

[Freddd]

Hi, freddd.

It really would be good to be able to compare the various protocols on the same basis to see which works the best in CFS. However, I think that in order to do this, we need to make sure that we are dealing with cohorts that are representative of the CFS population.

I understand that there has been considerable success with your protocol, but I continue to wonder how many of the people who have had this success would meet the Fukuda et al. or the Canadian case definitions for CFS. I note that a great deal of the experience with your protocol has been had by people on the B12 deficiency thread of the wrongdiagnosis forum.

I want to reiterate that I do not believe that B12 deficiency is synonymous with CFS. There are many subgroups of B12 deficient people, and I can understand how your protocol would be almost universal for them, because it bypasses the normal absorption, transport and processing of B12, so that whatever problems people might have in those areas, your protocol would leapfrog over them. I think that's wonderful, and I'm glad that your protocol has been able to help these people.

However, as you know, the focus here is CFS, and I think it is necessary to make sure we are talking about people with CFS when we make comparisons of the outcomes of different protocols for the treatment of CFS. So I'm sorry, but I just can't accept your conclusions unless you can show that your cohort actually represents people who have CFS. You may be correct in your conclusions, and I would like to know if you are, but I don't think your argument satisfies the requirements that would make it valid.

One other thing: You've suggested that treatment with the protocol that uses hydroxocobalamin does not help with the neurological or brain-related issues in CFS. However, in our clinical study of people who did meet the Fukuda criteria for CFS, we found that they reported a significant increase in "mental clarity," which I take to mean that this protocol did help their brain function.

Best regards,

Rich

Hi Rich,

I do want to thank you for engaging in a dialog though I'm sure that you may find it as frustrating as I do at times. You help me bring focus to this. I lost my last consulting /software contract in 2002 as I was having too many memory and cognitive difficulties in learning the new programming systems to keep my skills and software up to date. I also wasn't getting around well enough to do the half a dozen conferences a year that I needed to be able to do. About the same time my neurological deterioration had reached the point that I couldn't read on enough days that I could count on being participartory.

we found that they reported a significant increase in "mental clarity," which I take to mean that this protocol did help their brain function.

I continue to wonder how many of the people who have had this success would meet the Fukuda et al. or the Canadian case definitions for CFS. I note that a great deal of the experience with your protocol has been had by people on the B12 deficiency thread of the wrongdiagnosis forum.

The only definition of b12 deficiency we use is that the person has any of a long list of symptoms, usde a lot of such symptoms. The test definitions are near worthless. A responsiveness to a trial is the defining factor, a tiral that uses both active b12s and methylfolate plus other cofactors.

I was in no way limiting this to purely the issue of mental clarity. I include the the hyper-reactivity to stimuli of many varieties, the inability to focus the eyes, loss of visual brightness, loss of auditory brightness, hyper-responsivness to flavor and odor at the same times as loss of aspects of flavor and smell, mood changes, personality changes, auditory, olfactory, visual and multisensory hallucinations, loss of memory, loss of clarity, loss of cognitive abilities, poly neuropathy, in some people outright psychosis, neurological pain in arms and legs, numbness, loss of position sense, loss of vibration sense, llermites, loss of motor control, ataxia, multiple chemical sensitivities and so many more symptoms. These things slide easliy along a whole spectrum of changes and are rarely so neatly divided as somebody drawing a line and saying this is "x" and this is "not x".

Many of the people have CFS AND x and y and z and ?. They are not neatly selected out to fit in this category or another. Many are rejects and writeoffs like I was. They don't fit neaty into a limited pigeonhole having just the specified symptoms and nothing else. When they do get a nice pigeonhole diagnosis the treatment specified didn't work or didn't work well enough.

Most are clearly a superset of CFS/FMS, so much of a superset that the CFS/FMS may hardly be visible it is so obscured by other symptoms. So if they have to be limited to being "pure" cases they certainly don't fit. Many of them have such a diagnosis, CSF/FMS, from some doc or other but it often isn't considered the "main" problem. Some like me are told "You have too many symptoms to be believable". So what are we supposed to do? Willingly take all the psych drugs prescribed to make us accept our fates quietly and go home to die?

How many histories have you actually personally taken? I spent 10 years in the field selling life and health. I took a LOT of histories. I worked a lot of "substandard" cases. I took case histories the underwriters could count on. While this whole debate over healthcare has obscured the insurance business, I worked with companies that would bid competitively for people with medical pre-existing conditions. The catch was that what I put down on the history had to include everything that could possibly turn up, the underwriters had to depend upon it. There couldn't be anything left hiding in the woodwork. They would rather be snowed under with irrelevant things than miss one mortality affecting item. I placed all my cases. When one asks questions based on a questionaire many things don't turn up. For instance, if working on a checklist for a CFS or FMS diagnosis you will get exactly what you are looking for. What you won't get are all the symptoms that 20 years worth of doctors have been telling a person to ignore as "not important". They won't even remember that they have them until something sparks their memory. Diagnosis is a peculiar business, especially in the world of b12.

With b12 what country you live in makes a difference. In the USA with a b12 deficiency symptom list based on ceratin unavoidable things and those things generally responsive to cycbl and a low serum cutoff of 170 or so, more than 100 symptroms including most of the neurological symptoms of b12 deficiency are missed. In the UK with the NHS list based on hycbl and again a serum level avbout 160 or so certain other symptoms are considered important but again more than 100 symptoms are missed entirely, just not part of the definition and not expected to respond to hycbl. There are some differences between these two lists. Then go to Japan with a cutoff of 550pg/ml and scads of neurological symptoms on the b12 deficiency list and methylb12 as the expected theraputic b12. Then you go to India, a vegetarian society and levels so low they become very concerned with reproductive failure. There you find effects on fertility, male and female, on reproductive health, b12 content of ejaculate and how that correlates with serum level and all sorts of information found no where else in the world. In the USA they go to high tech answers for the reproductive failure and Viagra for the endothelieal failure. In india they look into the b12 deficiency causes of reproductive failure. You can buy a years worth of b12 for the cost of a single Vagra.

So in a weird and deadly version of To Tell The Truth will the real b12 deficiency please stand up. They all stand up because every single one of the definitions is a partial defiinition of b12 deficiency. When you include all of them you come up with a comprehensive definition of b12 deficiency that includes hundreds of symptoms, signs and co-correlates, only some of which are culturally important in any given country and limited to validating the specific form of b12 used in a specific administration program used in that country. So in the USA a person typicaly isn't going to find symptoms on the list that are not fixed by one cycbl injection per month. In the UK a person isn't going to find symptoms that are not fixed by a single hycbl injection each 1-3 months. If such symptoms are listed they are generally annotated that "Damage becomes permanent within X months of appearance".

Defining a disease as being that which a specific therapy can fix seems kind of crazy to me. Of course it would since it almost killed me. Since I was taking the theraputic oral dose of cycbl of 1000mcg orally daily whatever I had couldn't possibly be b12 deficiency. There was absolutely zero knowledge of the possiblity that cycbl might not be effective for me. Not 1 of more than 100 doctors knew of any such thing. When I mentioned the possiblity I was told flat out that I was absolutely wrong and that there was absolutely zero possibility of that being the case. I could have copies of the journal papers in my hands and it would not matter. Instead I was kicked out of practices.

In finding that I actually need methylfolate, methylcoblamin and adenosylcobalamin for full effectiveness in healing, along with other cofactors that enhance the effectiveness has to say something. Without the methylfolate, the effectiveness of the two b12s is not complete. This is something we run into over and over. A majority of people I am dealing with need methylfolate, not folic acid, in order for the active b12s to work. The majority need both active b12s for best effect. As you state the presumed genetic condition I have is too rare to account for that. So why do the majority need both active b12s and active folate to correct their problems?

So maybe there is something very wrong in the definition of b12 deficiencies. However, people shouldn't be deprived of life and health because of word and number games. They need to receive proper treatment that works rather than killed as a sacrifice to defintions.

Unlike the "steps" for treating pain there are no such things for b12 deficiencies. So if a minimalistic 1mg injection of cycbl/hycbl per month doesn't work there is no next step of 1mg of mb12 daily or 10mg mb12 3 times daily plus 1mg of adenosylb12 injected weekly or daily or anything else. So instead as the neurological damage gets worse the system gives them antipsychotics and antiseizure meds and antidepressants and send them home to continue deteriorating until they die hopefully without them complaining too loudly and upsetting others. Instead of stepping up the therapy they are redefined to have a different and unsolvable problem.

 

[dolo]

Hi Rich,

What methylation pathways panel test to you recommend? The only one I know about is the Dr. Yasko genetic test, $500, located at her Holistic Health website. I believe that is a swab that I send in to be evaluated. Would it be better or more accurate to have a blood test? My FFC Dr. is interested and was wondering if her office could take my blood for the test. The major progress I have made has been since January. I have been following the Freddd protocol.

I am not sure what grouping I belong to, CFS/Fibro or B12 deficiency or both. I'd be happy to share my results, if you're intrested.

I had been diagnosed with CFS and Fibromyalgia over 10 years ago and I have little to no digestion. My pain slowly became more intense over the years to the point of excruciating. My serum B12 was 607pg/ml in July 2008, after supplementing with the Enzymatic Therapy - Energy Revitalization for 6 months. Last year it was at 1200 pg/ml after continuing the Energy Revitalization supplementation. My pain was unaffected. One year ago, I received a vial of h-b12 and the shots did wonders for me but I ran out (I am located overseas) and the pharmacies don't carry it. It wasn't until I added folate, m-b12 and a-b12, etc. that my pain has finally begun to dissipate.

Thanks,
Dolo

 

[Cloud]

Hi, Big and Cloud.

I'm glad to hear that you have experienced benefit from hydroxocobalamin injections. Though I favor this form of B12 for the treatment of CFS, I am surprised that the other forms did not help you, also, since the cells can normally utilize any of the forms of B12 and convert them to what they need. This makes me wonder whether your cells might have a problem in removing the alkyl ligands (methyl and adenosyl) and maybe the cyano ligand, also. There is a particular gene product that normally carries out this removal, but mutations in it are thought to be fairly rare. So I'm a little puzzled by this, but glad the hydroxo B12 is working for you both.

Rich

Hi Rich, I wouldn't be the least bit surprised if my liver has a hard time pulling the ligands off, but I would suggest that at least in my case it may just have to do with the evolution of my disease process and healing. I have made a lot of changes since I last attempted B12 (Cyano and Methylcobalamin) about 3 years ago. The changes can be for better, or for worse, but they are changes. Plus, I have been involved in several interventions attempting to improve my health since last trying B12. I was on a heavy antiviral medication for all of 2009 which knocked some viral infections back down and allowed for some improvements. I just know from 16 years dealing with this monster that I can never be sure that what worked a year ago, will necessarily work today, and visa versa....that's been my experience anyhow. Maybe the Hydroxycobalamin wouldn't have worked either 3 years ago.

 

[Freddd]

Hi, Big and Cloud.

I'm glad to hear that you have experienced benefit from hydroxocobalamin injections. Though I favor this form of B12 for the treatment of CFS, I am surprised that the other forms did not help you, also, since the cells can normally utilize any of the forms of B12 and convert them to what they need. This makes me wonder whether your cells might have a problem in removing the alkyl ligands (methyl and adenosyl) and maybe the cyano ligand, also. There is a particular gene product that normally carries out this removal, but mutations in it are thought to be fairly rare. So I'm a little puzzled by this, but glad the hydroxo B12 is working for you both.

Rich

Hi Rich,

As somebody with extensive experience of not being able to convert one form of b12 to another, at least not with adequacy, I would loke to say thart it also applies to not being able to have sufficient adb12 from taking mb12 and not enough mb12 from taking adb12. The only time the actual adb12 and mb12 were made inactive was when I was taking glutathione proecursors and for 6 months after until I took a sizablwe dose, 4800mcg, of Metafolin daily thereafter. Within hours after taking the first larger dose of Metafoilin, I had been taking 800mcg, suddenly I had mb12 startup effects all over again when I took a dose of mb12 though Ihad been taking it daily. The same thing occurred later that day again when I had startup responses all over again from adb12 despite taking it reqularly the entire period.

So it is quite possible for other substances to inhibit responses to methylfolate, methylb12 and adenosylb12, and possaibly other forms as well. I find that taking the methylfolate concurrently with my mb12 and adb12 doses to be beneficial in both of their utilization, for reasons quite unknown to me. None of this is quite as cut and dried as we would like it to be.

A separate interaction occurred for me last week as well. I tried Pantethine. It caused a couple of days of a large amount of pain. I had tried doing without TMG and SAM-e a week earlier without ill effect. However, the pain caused by pantethine only occurs when I am not taking TMG and SAM-e. I restarted the TMG and SAM-e and retried the pantethine and it has no effect. This has really puzzled me.

 

[Freddd]

Yep, if it works, don't fix it, lol. But I am curious if I might get a good response with the SL Hydroxycobalamin (like the Perque B12). I have done many vials of IM Cyanocobalamin, and many different brands of SL Methylcobalamin all with no response at all...but the hydroxy form is new to me and since I responded so well to the IM, maybe the SL will be good too....it would certainly be less expensive.

I'm sure this has been discussed already somewhere (and the chemistry is over my head).....If Hydroxy and Methylcobalamin have different functions in the body, is supplementing only one form sufficient? Once in the body, does the Hydroxy B12 change structure to Methyl B12 to meet the methylation needs?

Hi Cloud,

If Hydroxy and Methylcobalamin have different functions in the body, is supplementing only one form sufficient

Adenisylcoblamin has the functions of prodicing ATP in the mitochondria, producing energy in essence. It is also invloved in some fatty acid transactions making the fat for myelin sheathing on the nerves and poor quality fatty acids there allow rapid breakdown. Methylcobalamin is active in the methlation reactions such as homocycgteine to methionine conversion, DNA replication, neurotransmitter generation, nerve functioning and 100% of other b12 functioning within the body. In certain non-b12 functions, such as certain chemical transactions such as detoxifying cyanide, all forms of b12 including hydroxycobalamin work except cyancobalamin. Hydroxycobalamin has no funtion within the body as b12 except to be converted in small quantities to the two active forms of b12.

I find that for most people taking both forms of the active b12s works best. There are some for whom methylb12 does not work at all that have to have adenosylb12. These are two separqate deficiencies in folks unable to convert. There are those for whom adenosylb12 do nothing and have to have methylb12. This occurs because of a lack of certain enzymes that cause the transformations. A person may have shortages of either kind of active b12 in the body and in the cerbral spinal fluid. For those with the shortages in the CSF a high serum level appears to be needed to force the cobalamin into the cerebral spinal fluid. For those people normal sublingual doses don't work because they don't cause a high enough serum peak causing a steep diffusion gradiant forcing the b12 into the CSF. That is the purpose of the large single dose test of the sublingual b12s. This is done with 50/51mg of the sublingual tablets as a single dose made to last for as long as possible, 2 hours if possible. While this is stretched out compared to a 1mg injection it can usually get high enough to make it into the cerebral spinal fluid. This has been tested as compared to 7.5mg mb12 injections SC. The SC injections cause a serum peak about as high as a 1mg IM injection but maintains it about 6 times as long. The 50/51mg SL test also allows a confirmation of absorbtion by being enough to be visible in the urine. Some people appear unable to absorb sublingually for reasons unknown but might be as simple as pH variations in the mouth.

As far as suublingual brands of b12, I tried a lot and only 2 were reaaly good. A few were mediocre and one was a total zero. I found tha there was more than a 100x difference by brand. The odds of finding an effective sublingual b12 by chance is very low.

Further if chewed and swallowed or slurped right down, absorbtion decxreases to the same 1% as oral and does very little. With SL tablets, percent absorbed is proportionate with time in contact with tissues. With the 5 star brqands we tested, 45 to 120 minutes produced urine coloration comparable to 7.5 to 12.5mg of mb12 injected SC, 15-25% absorbed approximately.

 

[jade]

Have there been any recommendations on supporting supplements in regard to forms that are better absorbed or specific Brands for; potassium, zinc, calcium/magnesium, Vitamins A, D, E, C, As well as for TMG and SAM-e?

 

[jade]

Thanks Wildaisy,
I've been on Dibencozide for 2 weeks now. I am mostly exhausted + having my eyes dont want to read for longer than about 10 minutes. I started searching iHerb for these things to order but are different forms etc. Was kinda hoping for maybe something like links to specific products.