B-12 - The Hidden Story

[powertool4]

Well after stopping the mb12 sublingual I improved alot and after stopping the b complex my dizziness is 10% of what is what last week, just to have this break is like heaven. Of course its too early to say if this is a freak occurrence although I doubt it. This leaves me in an awkward position as what to do next when even the b complex bothers me. Whats strange is that prior to the mb12 the b complex never effected me, why would that change? Trying to get my head around this just hurts I am not aware of allergies to any of the fillers all I know is I feel so much better right now.

I was thinking to leave it all for a week and then come back to it slowly. To give you an idea on the days I take the b12 I loose about 60% functionality.

I stuck to the plan for two months and really suffered with it hoping it would reduce in intensity but it just wont let up. Either Ive got to really slow it down this time and really ease into it as I cant go head first again as its literally torture.

The real concern I have is accepting that I am making the right move, even though it makes sense that I would get a reaction from healing I cant help but feel suffering with it is sensible either.

I was and is in the same boat as you. the mb12 helps but seems to aggravate a lot of things. It makes me so emotional, i get really bad brainfog from the mb12 (when im off i dont have brainfog), i get irritable, depressed and other things. Basically my symptoms worsened. but then again, i'm sleeping better and my adrenals are doing better as in i can handle stress better, i dont have heart palpitations anymore, etc. so it's kind of a tradeoff. sometimes i think, wow, this was a good trade off, gotta keep going. and other time i think, wtf i'm worse than i was before. The biggest thing about start the mb12 for me was, whenever i eat especially carbs or sugar i get REALLY REALLY bad brain fog, depressed, anxious and feel derealized. if i get off the mb12, doesnt occur so i dont know what the deal is. and i had to cut down the ab12 because even more than 200mcg for the day i can't sleep.

 

[Freddd]

I was and is in the same boat as you. the mb12 helps but seems to aggravate a lot of things. It makes me so emotional, i get really bad brainfog from the mb12 (when im off i dont have brainfog), i get irritable, depressed and other things. Basically my symptoms worsened. but then again, i'm sleeping better and my adrenals are doing better as in i can handle stress better, i dont have heart palpitations anymore, etc. so it's kind of a tradeoff. sometimes i think, wow, this was a good trade off, gotta keep going. and other time i think, wtf i'm worse than i was before. The biggest thing about start the mb12 for me was, whenever i eat especially carbs or sugar i get REALLY REALLY bad brain fog, depressed, anxious and feel derealized. if i get off the mb12, doesnt occur so i dont know what the deal is. and i had to cut down the ab12 because even more than 200mcg for the day i can't sleep.

Hi Powertool,

A major clue appears to come from the results with the adb12. Adb12 is really limited. It does only one thing in the body. It occupies a place in the mitochondria and participates in the generation of ATP, the body's energy "currancy".

Let's consider what that might mean. Control of metabolism is a multifactored thing. Let's suppose that your mitochondria had a 1% occupancy rate by adb12. If a dose raises that to 5%, that is a huge increase percentage wise. Before, your body was saying produce ATP at 100% rate all the time and still never have enough. So the throttle is set for 100%. Suddenly you take adb12. Now 5% are occupied and that 100% throttle now produces 5x more energy. It interfers in sleep and other things. It takes a while for the body mechanisms to adjust back to having that much energy and adjust the throttle accordingly. Switching from anarobic energy production that produces lactic acid which burns in the muscles to arobic energy production produces 6x more enegy from each reaction.

Coming back to normal is a huge shock to the system and takes a while to adjust. After the mitochiondria are 100% charged up with adb12, and this is where much of the body's working supply of b12 is, in the mitochondria, taking adb12 produces no noticable effect at all. It appears that keeping it high so that it seems like "too much energy" is what it takes to make the body readjust it's settings to take account of the new situation over time so that the body can readjust to the genuine "normal". Having mitochondria producing energy in all mitochondria allows the body to exercise, restores abilty to build up arobic endurance and normal exercise tolerance and to build muscle from exercise and to repair muscles.

When the mitochondria have adb12 in the neurological tissue it also affects how our brains and nerves work. It appears to make differences much more noticable and increases the strengths of emotions and moods. The balance between mb12 and adb12 and methylfolate, as well as b-complex and other factors appears to affect qualitative aspects of moods and emotions.

 

[powertool4]

Hi Powertool,

A major clue appears to come from the results with the adb12. Adb12 is really limited. It does only one thing in the body. It occupies a place in the mitochondria and participates in the generation of ATP, the body's energy "currancy".

Let's consider what that might mean. Control of metabolism is a multifactored thing. Let's suppose that your mitochondria had a 1% occupancy rate by adb12. If a dose raises that to 5%, that is a huge increase percentage wise. Before, your body was saying produce ATP at 100% rate all the time and still never have enough. So the throttle is set for 100%. Suddenly you take adb12. Now 5% are occupied and that 100% throttle now produces 5x more energy. It interfers in sleep and other things. It takes a while for the body mechanisms to adjust back to having that much energy and adjust the throttle accordingly. Switching from anarobic energy production that produces lactic acid which burns in the muscles to arobic energy production produces 6x more enegy from each reaction.

Coming back to normal is a huge shock to the system and takes a while to adjust. After the mitochiondria are 100% charged up with adb12, and this is where much of the body's working supply of b12 is, in the mitochondria, taking adb12 produces no noticable effect at all. It appears that keeping it high so that it seems like "too much energy" is what it takes to make the body readjust it's settings to take account of the new situation over time so that the body can readjust to the genuine "normal". Having mitochondria producing energy in all mitochondria allows the body to exercise, restores abilty to build up arobic endurance and normal exercise tolerance and to build muscle from exercise and to repair muscles.

When the mitochondria have adb12 in the neurological tissue it also affects how our brains and nerves work. It appears to make differences much more noticable and increases the strengths of emotions and moods. The balance between mb12 and adb12 and methylfolate, as well as b-complex and other factors appears to affect qualitative aspects of moods and emotions.

That is very interesting. I have actually done an organic acids test, urinary amino acids test and a metabolism test that showed my entire kreb cycle. My succinic acid was real low (which is explainable in the rupture in the cycle by lack of ab12 to convert methylmalonc into succinic) and because my succinic is low, my malate was non-existent/ZERO. So there is definitely a break in the kreb cycle. However, i had very low lactic acid and pyruvate which is the very beginning of the cycle, and that only come from carbohydrates. So i can only imagine that lack of carbohydrate (through malabsorption, i have gut issues) is also contributing to the energy production so i have low kreb activity to begin with. This explains a lot.

So what you are saying is that the reaction of being wired and unable to sleep, high energy caused by the ab12, is actually a side effect of starting up the mitochrondia at full speed and more? If this is true, how long (based on your exp) does it take for the body to adjust to the startup?

The other thing that does not make sense to me is how most people say that immediately following b12 after being deficient allowed their brain fog to clear and that they feel great. I feel the complete opposite. I feel that my head and mental issues are stable UNTIL i incorporate the b12. I only continue to use the b12 because it helps with other issues and i'm deficient. Maybe the issue in my case is not only b12, but of what forms i use and with what other supplements cause i seem to react differently than the average person out there. The depression and just complete emotional issues that come from the b12 is quite scary for me.

I guess basically, i just wanted to know if someone has sleeping issues from ANY b12 regardless of what it is, that's an indication that it is working and should be pushed through..?

 

[Sunday]

xlynx, the list of symptoms I mentioned is here, on page 3 of this thread. On that page are also some of Freddd's suggestions for titration, which you may find helpful.

My own titration was slow; I'd read about the awful effects and wanted to go easy, because I was already feeling bad.

Working off of Freddd's treatment plan (page 1 of this thread), I started with the "essentials" as a foundation, then started adding things from the "critical minimums" list one at a time. B-Right, then adb12 (seemed to have fewer dire effects, and one of my main problems was and is energy lack). I was going to divide the adb12 but the pills are so small I couldn't physically do it. For me, that was OK, for others, not.

I added mb12 very slowly, since I'd read about its weird (and often none too pleasant) effects on this thread. I started with 1/3 of a 1,000mcg tablet (couldn't cut it smaller). After the dust had settled, I went up to 2/3, then a whole tablet, then 1 1/3. After this I bumped up my dosage by 1mg until I reached 5mg. We're talking months, here. My most recent bumpup has been pretty drastic, testing F's theory that it's the first small doses that cause the greatest commotion. Well, I have felt like serious crap (OK, occasionally amusing crap) for the last week, but it's not as bad as I've known. And yes, a return of dizziness, orthostatic intolerance, PEM, brainfog, neuropathies, the whole shebang. That's what I mean by, it's not a linear process. It seems you have to get worse to get better.

During the process of upping the mb12 I also started the methylfolate. On the suggestion of David and Velha, I recently doubled my dosage on that, a rough ride but I think essential. I will probably be tinkering with this and the "possibly critical cofactors" for some time. It might have been smart to add the methylfolate before the b12s, as its essential to their action.

The thing about using Freddd's list of symptoms is that it can remind you that things are changing. For instance, in my 2-month crash all my symptoms were very bad, except my neuropathies. They'd always kicked up during crashes, but not this time. That told me something different was happening. Now my neuropathies are back, worst they've ever been as far as extent. I just have to trust that this is another level of healing. It's a SLOW process for me. I committed myself to 6 months of it and then a reassessment. I'm sticking with that. I may not see 95% improvement on this, as Freddd did, but methylation feels crucial to me.

 

[Sunday]

powertool4, insomnia's very common with mb12. In a discussion about that earlier in this thread, F suggested taking all your dosage before noon. Personally I can't tell mb12 insomnia from the insomnia I've had since the very beginning (or maybe even before the beginning) of this disease. I use marijuana oil, legal in my state, for a sleep remedy that's reliable and doesn't riddle my liver, which is having a hard enough time. It also helps with nerve pain, nausea, and the depression that's natural when your neurology is all over the place and you feel like crap.

I understand what you mean about the emotional changes and static; I'm going through a serious bout of that right now. In a way, it's a good thing: it's making me do energy work with emotional issues that are held in my body, because they're just so in my face I have to do something. Acupuncture, breathwork, meditation, Taoist energy exercises, are some other ways to work with it. Or let your intuition be your guide to finding ways to let emotions flow healthily. It is scary, but feels necessary.

As far as brain fog, every time I up my mb12, I get another round. The thing I notice, though, is that every time the quality of my brain fog is - lighter, better. And that in between my brain function definitely improves. People are different in how they respond to the mb12. When I had my 2-month starter crash, it was brain fog all the way through.

Freddd says that when we go through healing, our neurology gets rewired. This makes sense to me. I've spent a lot of time studying and working with some esoteric traditions; basically all of them have different methods of rewiring the synaptic pathways of the brain (at least that's how we say it in Western-medicine-speak). I'm doing my best to think of this as an opportunity to, shall we say, update my wiring and get rid of some of those funky rat-chewed old emotions and thought patterns that I don't need any more and which could be a danger to the whole house.

 

[powertool4]

powertool4, insomnia's very common with mb12. In a discussion about that earlier in this thread, F suggested taking all your dosage before noon. Personally I can't tell mb12 insomnia from the insomnia I've had since the very beginning (or maybe even before the beginning) of this disease. I use marijuana oil, legal in my state, for a sleep remedy that's reliable and doesn't riddle my liver, which is having a hard enough time. It also helps with nerve pain, nausea, and the depression that's natural when your neurology is all over the place and you feel like crap.

I understand what you mean about the emotional changes and static; I'm going through a serious bout of that right now. In a way, it's a good thing: it's making me do energy work with emotional issues that are held in my body, because they're just so in my face I have to do something. Acupuncture, breathwork, meditation, Taoist energy exercises, are some other ways to work with it. Or let your intuition be your guide to finding ways to let emotions flow healthily. It is scary, but feels necessary.

As far as brain fog, every time I up my mb12, I get another round. The thing I notice, though, is that every time the quality of my brain fog is - lighter, better. And that in between my brain function definitely improves. People are different in how they respond to the mb12. When I had my 2-month starter crash, it was brain fog all the way through.

Freddd says that when we go through healing, our neurology gets rewired. This makes sense to me. I've spent a lot of time studying and working with some esoteric traditions; basically all of them have different methods of rewiring the synaptic pathways of the brain (at least that's how we say it in Western-medicine-speak). I'm doing my best to think of this as an opportunity to, shall we say, update my wiring and get rid of some of those funky rat-chewed old emotions and thought patterns that I don't need any more and which could be a danger to the whole house.

Hi, thanks for the response.
I actually don't get insomnia from mb12. Mb12 makes me depressed, both mentally and systematically. My entire body feels heavy, i feel tired, mentally i get real depressed. The funny thing is that it doesnt happen immediately. It usually kicks in about 3-5 days after starting mb12. I have tried this over and over at least 5 different times now and it is just the way my body reacts to it. I don't know what it is.

Ab12 AND hydroxyb12 does the opposite, in that i get pretty wired and get insomnia from it. better energy though, and all that but the "wired but tired" feeling. It is really two extremes. When i was testing out the ab12/hydroxyb12 all i wanted to do was switch over to mb12 so i can get some sleep. I didn't take into consideration that my body might need adjusting to the ab12 or hydroxy b12s.

The mental issues with mb12 is very hard to describe. it feels like my brain if frying, with too many neurotransmitters. though this is not widely accepted and still variable, overmethylators tend to not do well on mb12 (shown in CFS and autism patients) for some reasons and one reason being an overload or too many neurotransmitters being produced. That's what my brain feels like right now. Too many neurotransmitters feels different than not having enough, it is very hard to explain. Overmethylators also have a lack of GABA and low histimine. I don't know my histimine levels but my histidine was extremely low and indicates a need for folate. my general tendencies suggest highly overmethylator. Now, i understand this goes against the active b12 protocol but at this point, I myself have to make a judgment call here to see what's going on. Judging from the posters and getting feedback from others, as well as personal research and experience.. my case seems to be different from the average person and i do not tolerate mb12 well at all no matter what i try. I even went in strong and tried to brush it off and added methylfolate, and then switched to folinic to see if that would make a difference and the side effects eventually caught up to me today. I was home alone, crying and bawling and doing things that are DEFINITELY not normal for me. depression is something that is not normal for me. Anxiety, paranoia or a tendency to be more higher energy is more me.

I am thinking about trying either ab12 or hydroxy b12 by itself and push through the "wired" and insomnia feelings and see if my body does infact adjust. I might slip methyl in every once in a while.

 

[Sunday]

I think this disease is different in everyone, and you are the best judge of your own health. I will say that Freddd has repeatedly pointed out that, at least for most people, if you quit taking mb12 before you've gone all the way through the startup effects, the next time you start mb12, you just repeat the same effects. The only way out is through.

Would it make sense to test your methylation, so you have a better idea what's actually going on?

 

[Freddd]

That is very interesting. I have actually done an organic acids test, urinary amino acids test and a metabolism test that showed my entire kreb cycle. My succinic acid was real low (which is explainable in the rupture in the cycle by lack of ab12 to convert methylmalonc into succinic) and because my succinic is low, my malate was non-existent/ZERO. So there is definitely a break in the kreb cycle. However, i had very low lactic acid and pyruvate which is the very beginning of the cycle, and that only come from carbohydrates. So i can only imagine that lack of carbohydrate (through malabsorption, i have gut issues) is also contributing to the energy production so i have low kreb activity to begin with. This explains a lot.

So what you are saying is that the reaction of being wired and unable to sleep, high energy caused by the ab12, is actually a side effect of starting up the mitochrondia at full speed and more? If this is true, how long (based on your exp) does it take for the body to adjust to the startup?

The other thing that does not make sense to me is how most people say that immediately following b12 after being deficient allowed their brain fog to clear and that they feel great. I feel the complete opposite. I feel that my head and mental issues are stable UNTIL i incorporate the b12. I only continue to use the b12 because it helps with other issues and i'm deficient. Maybe the issue in my case is not only b12, but of what forms i use and with what other supplements cause i seem to react differently than the average person out there. The depression and just complete emotional issues that come from the b12 is quite scary for me.

I guess basically, i just wanted to know if someone has sleeping issues from ANY b12 regardless of what it is, that's an indication that it is working and should be pushed through..?

Hi Powertool,

I added methylb12 to what I was already taking, all the basics including omega3 oils. After 9 months I added the adb12. I, like many people here, had a separate reaction to adb12 from mb12. With the mb12 I did get partial mitochondria startup and the burning lactic acid pain went away within 10 days. However, a different kind of muscle pain and spasms and healing and groth did not accur for the entire 9 months. Each day I while taking thew sublingual I had an energetic jolt all over again. It went on and on. After 3 months of that not including the month of going backwards with inferior brands, I wondered what would finally put a stip to it. I started escalating the methylb12. 1-5mg a day just had continued the startup indefinitely. When I went from 5 to 10mg it was a jolt but each day the size of the jolt faded a little. When that was gone an increase to 15mg gave a smaller jolt that faded faster. By the time I reached 25mg there were no more jolts and the startup was over. I had reached an equilibrium with no further change eachg tiome I took a dose.

At 9 months I bought Country Life. I had a sizable jolt all over again, larger than anything I had except those first 3 months of 1-5mg of mb12. The second day on the adb12 the jolt was much smaller. After 5 days it was non existant, even taking 3 or 4 of them. Before that I had been sleeping lightly. I had sleep problems for 25 years before hardly sleeping more than 5 hours most nights. Whe I started in pain management I slept a bit better. After several months on the mb12 I started sleeping great. When I started the methylfolate several years later I started dreaming again for the first time in decades. After the adb12 I was up to almost full energy, my muscles healed and I slept great. And when methgylfolate was started that finished all my sleep problems with restored dreaming. For the years of the deficiency I had a prolonged hypnogogic state and had a difficult time transitioning to full sleep.

 

[xlynx]

I also find my head and brain function is stable until I take the mb12. It causes dizziness, brain fog and mood problems for me too. I also find that it is a mb12 specific brainfog it is different to the other type I get it feels like a lack of blood flow to my head.

Since stopping the mb12 I have come back to my baseline, frustrated that I coudnt continue on but I will titrate now using the guide.

Whats the best way to test my methylation? Is it reliable and worth doing?

 

[richvank]

I also find my head and brain function is stable until I take the mb12. It causes dizziness, brain fog and mood problems for me too. I also find that it is a mb12 specific brainfog it is different to the other type I get it feels like a lack of blood flow to my head.

Since stopping the mb12 I have come back to my baseline, frustrated that I coudnt continue on but I will titrate now using the guide.

Whats the best way to test my methylation? Is it reliable and worth doing?

Hi, xlynx.

In my opinion, the best way to test the operation of the methylation cycle is to get the Vitamin Diagnostics methylation pathways panel. Dr. Nathan and I used it in our clinical study of 30 women, 21 of whom satisfied strict criteria for CFS, and most of whom also met criteria for fibromyalgia. The women were given this panel initially and at 3, 6, and 9 months. The results were consistent with significant improvement over time on the Simplified Treatment Approach (which uses hydroxocobalamin rather than methylcobalamin), and the self-rated symptoms severity also showed significant improvement. The contact information for this panel is posted below. The lab is currently finishing the process of moving to a different building, so is not up in full operation yet, but hopefully will be soon.

It's difficult to tell from symptoms alone how the treatment is going, because detox and die-off of pathogens as a result of improved function of the detox and immune systems can cause symptoms during the treatment.

As you may know, we have had some discussion on this thread in the past about the known ability of methylB12 to react with inorganic mercury to form methyl mercury, which can cross the blood-brain barrier and enter the brain. I have no proof that this actually occurs significantly at the dosages of mb12 used in freddd's protocol and the body burdens of inorganic mercury in PWCs, and he does not believe that it is an important issue. However, it would be interesting to me to know whether you would experience the same type of brain fog if you used hydroxocobalamin rather than methylcobalamin. The Simplified Treatment Approach suggests Perque sublingual hydroxocobalamin at 2 mg.

I will also mention that my position is that a person must be monitored by a physician while on treatment to lift the partial methylation cycle block in CFS in order to make sure that if any serious adverse effects arise, they can be recognized and dealt with promptly. Some of these appeared in a small number of PWCs who first tried the Simplified Treatment Approach in early 2007. Some appeared to be due to the presence of other, comorbid conditions, in addition to CFS.

Best regards,

Rich


Methylation Pathways Panel

This panel will indicate whether a person has a partial methylation cycle block and/or glutathione depletion. I recommend that this panel be run before deciding whether to consider treatment for lifting the methylation cycle block. I am not associated with the lab that offers this panel.

The panel costs $300 and requires an order from a physician or a chiropractor. The best way to order the panel is by fax, on your clinician’s letterhead.


Available from:

Vitamin Diagnostics, Inc.
540 Bordentown Avenue
South Amboy, NJ 08879
USA
Phone:+1 (732) 721-1234


Lab Director: Tapan Audhya, Ph.D.
(usually at the lab on Tues. and Wed. from 1 to 3 p.m., Eastern time)

Dr. Audhya is willing to help clinicians with interpretation of the panel by phone.

 

[markmc20001]

the mb12 helps but seems to aggravate a lot of things. It makes me so emotional, i get really bad brainfog from the mb12 (when im off i dont have brainfog), i get irritable, depressed and other things.

Heya powertool, obviously freddd and rich are the pros here, I'm a struggling patient. But I have had that same type of thing happen in my body. But I have a gut feelign so to speek. But taking antibiotics, antifungals, and MB12 can cause those symtpoms for me too. here is my wild guess hypothesis:

1) Maybe the cells are starting to create energy? but the low glutathione (caused by who knows what) is not allowing the body's cells eliminate the spent fuel and other toxins (exhaust)???? My wild hypothesis!!(based on what I read from rich and others) OSR#1 may help boost the glutathione to get rid of that toxic exhaust in the cells and improve your brain fog associtaed with the toxins being created when the cells create energy ???It probably depends on your body chemistry and diet, and supplements though and your results likely be different from everybody elses, but similar in some ways too

2) metals being relased into the bloodstream, and maybe reabsorbed if not good elimantion (maybe try fiber with a little olive oil on board. and also make sure ones GI tract is functioning. I use Magnesium and vitamin C until things get moving). OSR#1 may help with this too

3) endotoxins from dying fungus and bacteria: (maybe try saunsa, fiber, elimination)

yeah, so that sums it up. stuff not getting out of the cells making us feel bad. :headache:

 

[Sunday]

Freddd, Thanks for putting up your experience with moving into higher doses of mb12. I just spent the last week going from 5mg to 10mg (and for kicks, yesterday I added another 3mg of adb12, for a total of 9mg. Adb12 doesn't seem to have a lot of the heavier startup symptoms for me). You've probably written about this before, but I'm glad you did again as it's encouraging to me; at up to 5 mg I really have felt still pretty much on startup a lot of the time.

My repeated experience with mb12 brainfog is that, after I adjust to the higher levels of mb12, I can think better than before. In fact, this is my experience with other startup symptoms as well: the thing that gets exacerbated is the thing that's getting better.

 

[Sunday]

xlynx, I thought your description of the mb12 brainfog quality was interesting. I wouldn't have described it that way, but I know what you mean: there is a different quality to mb12 brainfog and it does feel a little lightheaded.

 

[Freddd]

Hi Rich,

Do you have easy access to NMR, mass spectrometer etc that could let you distinguish the subtle differences between several samples of mb12 exposed to varying amounts and types of light compared to a sample not so exposed, especially enough to change the biological response?

 

[xlynx]

Hi, xlynx.

In my opinion, the best way to test the operation of the methylation cycle is to get the Vitamin Diagnostics methylation pathways panel. Dr. Nathan and I used it in our clinical study of 30 women, 21 of whom satisfied strict criteria for CFS, and most of whom also met criteria for fibromyalgia. The women were given this panel initially and at 3, 6, and 9 months. The results were consistent with significant improvement over time on the Simplified Treatment Approach (which uses hydroxocobalamin rather than methylcobalamin), and the self-rated symptoms severity also showed significant improvement. The contact information for this panel is posted below. The lab is currently finishing the process of moving to a different building, so is not up in full operation yet, but hopefully will be soon.

It's difficult to tell from symptoms alone how the treatment is going, because detox and die-off of pathogens as a result of improved function of the detox and immune systems can cause symptoms during the treatment.

As you may know, we have had some discussion on this thread in the past about the known ability of methylB12 to react with inorganic mercury to form methyl mercury, which can cross the blood-brain barrier and enter the brain. I have no proof that this actually occurs significantly at the dosages of mb12 used in freddd's protocol and the body burdens of inorganic mercury in PWCs, and he does not believe that it is an important issue. However, it would be interesting to me to know whether you would experience the same type of brain fog if you used hydroxocobalamin rather than methylcobalamin. The Simplified Treatment Approach suggests Perque sublingual hydroxocobalamin at 2 mg.

I will also mention that my position is that a person must be monitored by a physician while on treatment to lift the partial methylation cycle block in CFS in order to make sure that if any serious adverse effects arise, they can be recognized and dealt with promptly. Some of these appeared in a small number of PWCs who first tried the Simplified Treatment Approach in early 2007. Some appeared to be due to the presence of other, comorbid conditions, in addition to CFS.

Best regards,

Rich

Hi Rich,

Thank you for replying.

Can I get this done even though I am in the UK? I have had a cfs profile test from acumen and that had showed that my glutathione was low and I had blocking of active sites etc. Is that enough to confirm a methylation block or do you think I should still look at the test?

From my limited understanding, am I right in saying that Hydroxy b12 has to be converted by the body into either of the active forms, and so then am I presuming the plan behind Freds protocol is to go straight for active b12s and to avoid the possibility that the body cant make the conversion? So if I was to take hydroxy b12 and had no obvious effect after a period of weeks what would be the most likely deduction, that I couldnt make the conversion or that the mb12 was causing an interaction with perhaps mercury binding or another unknown factor or that I was detoxing to heavy? If I did have the same reaction from hydroxy b12 as I did with the mb12 would that then mean?

I know these are hypothetical questions and I appreciate I should just probably do exactly as you suggested and get the test and then take a view, but I never did do anything in the right order.

Many thanks,

Jerry

 

[Freddd]

I also find my head and brain function is stable until I take the mb12. It causes dizziness, brain fog and mood problems for me too. I also find that it is a mb12 specific brainfog it is different to the other type I get it feels like a lack of blood flow to my head.

Since stopping the mb12 I have come back to my baseline, frustrated that I coudnt continue on but I will titrate now using the guide.

Whats the best way to test my methylation? Is it reliable and worth doing?

Hi Xlynx,

When does this happen? Does it happen within 15 minutes of starting a sublingual? Or 1 hour or two hours? Or after several days of taking it daily or after a month? Is it dose related? Does it happen faster if you take more?

Certainly "light headed", dizzy, differently aware, emotional changes, emotional volitility are things that can occur from the first day and extend for some months. Mb12 affects directly many things in the nerves at all levels, peripheral and central, including transmission speeds and changes hormones and neural transmitters. These things can all be found in research that has looked for such. Generally around 3 months a different set of characteristics appears as emotions become more volitile, personality changes, especially if there were personaility changes going into the deficiency, memory improvement, processing of built up unprocessed emotional items from years of shutdown. How things are perceived is directly affected.

For 20 years I was irritable and had terrible memory problems, cognitive problems, personality change (Mr Hyde) and all that. After nearly 7 years, Dr Jeckyl is back, memory is improved and as good or better than most and mostly restored, cognitive functioning is back and the backlog of emotional processing is cleared. Everybody that has had a lot of changes going in has had a lot of these effects coming out. These effects appear to reflect the amount of damage already done.

Generally I have observed that the worse the changes and the longer a person has been ill, the larger and more pronounced are the changes produced by mb12. After the stormy period things improve and the person emerges with many changes. This can also happen following each time some cofactor is added that increases or changes the effectiveness of mb12, such as methylfolate, l-carnitine, zinc, adb12, SAM-e.

What I do know is that many people who have reported similar things in the first months to a year or so have found that it clears and that they have had a lot of healing when it is gotten through. I would offer the possibility that everything you are experiencing is due to changes that will be beneficial when they are done. It could be due to all sorts of things because mb12 does affect immune function, neurolgy, metabolism, hormones and a whole lot else. I was under a doctors care as I went through all of it, an internist, but aside from tests each month he mostly watched. He had me increase potassium at one point. He was very interested to find that after 9-12 months I was able to discontinue in a controled fashion many of the medications I had previouly found necessary to get through the day; valium, lorazapam, dilantin, compazine suppositories, Albuterol, provigil, allowing me not to fall alseep at dinner etc also acted as an antidepressant, the only one that worked.


For instance, methylb12, SAM-e, methylfolate have all been shown to decrease depression. It is my impression that the first one taken has the most effect on depression, the second thing taken has the next most effect and so on. So for me methylfolate, the last critical factor added, made an incremental change, but only on a few things that were unaffected by the mb12/SAM-e/Carnitine/adb12 etc.

I'm not sure what you are experiencing.

Good luck.

 

[richvank]

Hi Rich,

Do you have easy access to NMR, mass spectrometer etc that could let you distinguish the subtle differences between several samples of mb12 exposed to varying amounts and types of light compared to a sample not so exposed, especially enough to change the biological response?

Hi, freddd.

Sorry, no I don't. I think that would be a very interesting thing to do, though.

On another subject, yesterday I was able to spend half the day at the UCSF medical library, and was able to look up the recent literature on a few topics. I may not be telling you anything you don't already know, but here are some things I think I learned there:

1. I looked at the recent papers on the mutations in the intracellular B12 processing enzymes. I learned that there are two labs, worldwide, who have identified most of the reported cases of these various mutations. One of the labs is at McGill University in Canada, and the other is in Switzerland. About 400 cases of these mutations have been found so far, worldwide, as of 2009. Of course, there are no doubt many cases that have not been tested, especially in the underdeveloped countries. Nevertheless, 400 cases worldwide is a very small number compared to an estimated million or so cases of CFS in the U.S. alone. In view of these numbers, I continue to believe that only a small fraction of those with CFS have one of these mutations. This doesn't mean that I think your protocol won't work for people with CFS, which it clearly does. As I've written before, I think your protocol will work for people with a wide variety of B12 issues at various steps of absorption, transport and processing. It's just that I think your case is different from that of most PWCs, and I think these numbers support that.

2. There are eight known proteins or protein complexes that are involved in the intracellular processing of B12, and each is known to be able to have one or several possible genetic mutations, which have been characterized in terms of their effects on the availability of either methylcobalamin or adenosylcobalamin or both, and thus on the levels of residual homocysteine and/or methylmalonate in the urine.

3. I looked at the most recent papers on treatment of these mutations. Even the most recent of them do not discuss use of forms of B12 other than hydroxocobalamin, and the dosages are considerably lower than those you have used and are recommending. In addition, they report that not all cases are helped by these treatments. I think these people would benefit by knowing of your treatment and the success you have had with it. If they did, I think they might be able to help more people, particularly babies, who have the more severe forms of these mutations.

4. The normal processes of absorption, transport and intracellular processing of B12 are becoming better understood. There are still some aspects of the intracellular processing pathways that are not completely explained yet, though. The 8 proteins and the genes that code for them have been identified, but it is not yet understood just how some of them function in the B12 processing.

5. Glutathione, together with a glutathione transferase enzyme, appears to be involved in removing ligands such as methyl- from the cobalamin molecule. You have reported that glutathione or its precursors were detrimental in your case. I suspect that the reason may be that the glutathione assisted in removing the methyl group from methylcobalamin, and that because of your particular genetics, your cells were not able to put the methyl group back onto the cobalamin molecules. This is believed to occur normally after cobalamin binds to methionine synthase, by the action of methionine synthase reductase, which receives a methyl group from SAMe, and which also needs both B2 and NADH. In view of this, and in view of the benefit you also receive from direct supplementation of adenosylcobalamin, I suspect that you have a mutation of the cblC type. This involves the protein complex that removes the beta ligand, such as methyl-, chemically reduces the cobalamin molecule, and then transfers it either to go to methionine synthase or to the mitochondria for the final conversion to the respective coenzyme forms.

5. So far, I have not been able to find any research on how B12 that is not bound to transcobalamin in the blood (as occurs when larger, milligram-level dosages are used) is transported into the cells, and what their pathways are once they are inside the cells. In the normal processing of B12 in the cells, it appears that the B12 comes in via a specific transcobalamin receptor in the cell membrane, and from that point on it appears that the B12 is carefully chaperoned during its processing and transport either to methylmalonyl CoA mutase in the mitochondria or to methionine synthase in the cytosol. But when the B12 comes into the cell by another route (perhaps by diffusion through the cell membrane), its pathways are likely to be different, unless chaperone molecules can bind to them directly. This stuff may be known, but if so, I haven't found it yet. My best guess at this point is that your treatment, with the several-milligram sublingual dosages of both coenzyme forms of B12, just bypassesl the normal absorption and transport pathways for B12, and simply diffuses through the cell membranes into the cells. Once inside, I don't know if chaperones bind to it or not. Based on your experience with glutathione, it appears that it is at least able to react with glutathione once inside the cells, but I just don't know the details of the pathways in this case yet.

Best regards,

Rich

 

[Freddd]

Hi Rich,

Thankyou for all that info. As you are so well aware it brings up more questions than answers as always.

I intend to do a comparison in naked eye biological effects of mb12 injection solution which is exposed to varying amounts of different light sources with intensity and duration of exposure. I know of others with similar responses. This is possible now that I have available a sufficiently large and inexpensive source of mb12 from a single excellent quality batch. If you would be willing to help me with the experimental design I would appreciate that though I have no money to pay consulting fees. This is a question that only arises from use of mb12 injections by those sensitive to those differences. Somebody who has never experienced that would never think to ask the question.

I have been sure that there are multiple variations of severity of these problems. I was able to limp along as long as I ate enough meat. When I tried large amounts of dessicated liver the "lights came on" in a way I had never experienced in my entire life. When I was an infant I received cows milk formula which did include a small amount of natural b12 and had solid foods added early so, aside from delayed myelination, I did not have terribly severe consequances. I was never healthy but also never in severe trouble. People like me would never show up in their statistics on these problems. Before antibiotics I would never have survived infancy but cause of death would have been pneumonia or rheumatic fever most likely.

Most of the folks here and at another forum have definite and different responses to adb12 and mb12, even after sufficiency of one kind. Why?

This includes those who have gotten into trouble via known ways, ie vegetarian, and who do respond well to hydroxyb12. WHY? Even those who respond well to hydroxyb12 have a much larger response to unbound mb12 and unbound adb12.


I looked at the most recent papers on treatment of these mutations. Even the most recent of them do not discuss use of forms of B12 other than hydroxocobalamin, and the dosages are considerably lower than those you have used and are recommending. In addition, they report that not all cases are helped by these treatments. I think these people would benefit by knowing of your treatment and the success you have had with it. If they did, I think they might be able to help more people, particularly babies, who have the more severe forms of these mutations.

Did you happen to note down the correspondence authors and emails? Via Google scholar I found a number of McGill papers connected to cblC which is a place to start if you don't have specific ones in mind. Also, if you have any suggestions on how to approach them in a way that they might find credible I would find that helpful.

With this specific problem, lack of conversion enzymes, why would they even expect hydroxyb12 to work? It seems so obvious that one would use the forms that don't need conversion in that case specifically.


In some of the papers I've read the failure to respond rate was in the 40-66% range for some varietries of the mutations. This is about twice the rate of failure of response in the "normal" population. Why is a 20-40% failure to respond rate to hydroxyb12 normal? What is the failure mechanism? Even when methylb12 is used the failure to respond rate is up to 20% or so at the doses used. Unfortunately I have not seen any study using BOTH active b12s much less with methylfolate. This leads me to hypothecize that there is a separate transport or other mechanism separate from the lack of conversion enzymes that leads to a large scale failure to respond like this.

The glutathione (precursors) appears to affect methylfolate even more than methylb12. What could be the mechanism for that? Again, I have folate deficiency symptoms while taking folic acid. Many people have this response. It is not at all rare and has happened to multiple people on most forums. However, I was the worst affected for the longest time. A year afterwards I still have rapidly displayed deficiency symptom(s) if I decrease my methylfolate dose to 3200-4000mcg a day from 4800mcg. Previously I found 800mcg fully effective for several years.


So far, I have not been able to find any research on how B12 that is not bound to transcobalamin in the blood (as occurs when larger, milligram-level dosages are used) is transported into the cells, and what their pathways are once they are inside the cells. In the normal processing of B12 in the cells, it appears that the B12 comes in via a specific transcobalamin receptor in the cell membrane, and from that point on it appears that the B12 is carefully chaperoned during its processing and transport either to methylmalonyl CoA mutase in the mitochondria or to methionine synthase in the cytosol. But when the B12 comes into the cell by another route (perhaps by diffusion through the cell membrane), its pathways are likely to be different, unless chaperone molecules can bind to them directly. This stuff may be known, but if so, I haven't found it yet. My best guess at this point is that your treatment, with the several-milligram sublingual dosages of both coenzyme forms of B12, just bypassesl the normal absorption and transport pathways for B12, and simply diffuses through the cell membranes into the cells. Once inside, I don't know if chaperones bind to it or not. Based on your experience with glutathione, it appears that it is at least able to react with glutathione once inside the cells, but I just don't know the details of the pathways in this case yet.

There appear to be two distinct levels of this penetration, body and CNS/CSF. I too have favored the diffusion hypothesis. An abundence of methylfolate appears to facilitate/augment this diffusion/penetration in some way. Also, adb12 and mb12 appear to be additive in this diffusion effect at the CNS level.


Several of us were searching for a paper that would explain how it goes outside the HTC mechanism but haven't found one either. This is an example how work with largely inactive cobalamins has affected the assumptions behind the research. I have not found any papers on the effects of an abundence of unbound active cobalamins. The only hints of it appears in papers in which the protocol explores the differences in response between low dose and high dose methylb12 (ie 120mcg and 1500 mcg) and in which a dose proportionality is demonstrated without exploring the "why" of dose proportionality.

I think your protocol will work for people with a wide variety of B12 issues at various steps of absorption, transport and processing. It's just that I think your case is different from that of most PWCs, and I think these numbers support that.

As far as I can tell most of the difference is in severity, but not types of reactions. Everything hits me harder quicker and lasts longer. I am immediately aware, within hours any way, of qualitative differnces between different batches of mb12 injection solution. Before I started injections or after being off them for 3-5 days I can tell the differences between sublingual brands qualitatively within often less than 1 hour.

Here is at least one article that appears to go to the heart of matters. It's too new to be free.
http://www.nature.com/nchembio/journal/v4/n3/abs/nchembio0308-158.html
Nature Chemical Biology 4, 158 - 159 (2008)
doi:10.1038/nchembio0308-158

Delivery of tailor-made cobalamin to methylmalonyl-CoA mutase





Vahe Bandarian1

1. Vahe Bandarian is in the Department of Biochemistry and Molecular Biophysics, 1041 East Lowell Street, Tucson, Arizona 85721, USA. e-mail: vahe@email.arizona.edu

Abstract

Methylmalonyl coenzyme A mutase (MCM) catalyzes the adenosylcobalamin-dependent isomerization of methylmalonyl-CoA to succinyl-CoA. Adenosyltransferase, an enzyme that carries out the final step in biosynthesis of adenosylcobalamin, is shown to be involved in delivery of the cofactor to MCM.


And another article with bearing, this one available as a free download.
http://www.nature.com/jp/journal/v23/n5/pdf/7210955a.pdf
Journal of Perinatology (2003) 23, 384–386. doi:10.1038/sj.jp.7210955
Potential for Misdiagnosis Due to Lack of Metabolic Derangement in Combined Methylmalonic Aciduria/Hyperhomocysteinemia (cblC) in the Neonate

Presented in abstract form at the Annual Meeting, American College of Medical Genetics, March 8–12, 2000, Palm Springs, CA, USA. Published as: Gibson K, Steiner R, Grompe M, et al. Potential for clinical misdiagnosis of combined methylmalonic aciduria/homocysteinemia (MMA/HCYS) due to absence of acute metabolic derangement. Genet Med 2000;2:62.


Cary O Harding MD1,2, De-Ann M Pillers MD, PhD1,2, Robert D Steiner MD1,2, Teodoro Bottiglieri PhD3, David S Rosenblatt MD, PhD4, Jason Debley MD5 and K Michael Gibson PhD1,2

1. 1Department of Pediatrics Oregon Health & Science University, Portland, OR, USA
2. 2Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR, USA
3. 3Institute of Metabolic Disease, Baylor University Medical Center, Dallas, TX, USA
4. 4Departments of Human Genetics, Medicine, and Pediatrics, McGill University, MUHC, Montreal, Quebec, Canada
5. 5Department of Pediatrics, Legacy Emanuel Children's Hospital, Portland, OR, USA

Correspondence: Cary O. Harding, MD, FACMG, Oregon Health & Science University, 707 SW GAINES Road, CDRC-F, Portland, OR 97239-2998, USA.

Top of page Abstract

We report two infants with an inborn error of cobalamin (vitamin B12) metabolism whose clinical presentation in the first month of life strongly suggested bacterial or viral sepsis. The absence of any acute metabolic derangement (acidosis, hyperammonemia, hypoglycemia, or ketosis) in association with clinical features suggesting sepsis (lethargy, obtundation) could impede the correct diagnosis of cobalamin C (cblC) disorder. In addition, this is the first documentation of cerebrospinal fluid hyperhomocysteinemia in cblC defect that was highly increased and is likely to be associated with neurotoxicity in cblC patients.

 

[Freddd]

Hi Rich,

Thank you for replying.

Can I get this done even though I am in the UK? I have had a cfs profile test from acumen and that had showed that my glutathione was low and I had blocking of active sites etc. Is that enough to confirm a methylation block or do you think I should still look at the test?

From my limited understanding, am I right in saying that Hydroxy b12 has to be converted by the body into either of the active forms, and so then am I presuming the plan behind Freds protocol is to go straight for active b12s and to avoid the possibility that the body cant make the conversion? So if I was to take hydroxy b12 and had no obvious effect after a period of weeks what would be the most likely deduction, that I couldnt make the conversion or that the mb12 was causing an interaction with perhaps mercury binding or another unknown factor or that I was detoxing to heavy? If I did have the same reaction from hydroxy b12 as I did with the mb12 would that then mean?

I know these are hypothetical questions and I appreciate I should just probably do exactly as you suggested and get the test and then take a view, but I never did do anything in the right order.

Many thanks,

Jerry

Hi Jerry,

From my limited understanding, am I right in saying that Hydroxy b12 has to be converted by the body into either of the active forms,

Actually you need BOTH forms, and you can have plenty of one while being deficient in the other.

and so then am I presuming the plan behind Freds protocol is to go straight for active b12s and to avoid the possibility that the body cant make the conversion?

The conversion to active is only one of the places for things to go wrong. The entire transport system is filled with hazard with many ways to not work. Conversion is only one of the possible problems.


So if I was to take hydroxy b12 and had no obvious effect after a period of weeks what would be the most likely deduction, that I couldnt make the conversion

That is only one possiblity. Another possibility is that since only 10-30mcg a day can be transported and converted it is possible that 10-30mcg each day just doesn't do the trick for you. The effects of having an abundance of unbound active cobalamins is often 100x as powerful as having a few mcgs of bound cobalamins. It means everything that needs cobalamins gets it rapidly instead of via a bodily triage that stingily doles out the cobalamins one molecule at a time and may take years or a lifetime to fill some needs. Hydroxyb12 only produces ZONE 1 effects typically, without dose proportionality. Picture taking 1mg of pennacillan a day when your body needs 500mg 3x per day to actually kill the bacteria. It heals things slowly, if at all, and rarely completely. Or maybe you can transport the b12 sufficiently. I have never yet seen a single person on inactive cobalamins who has all the need for b12 completely met so that adb12 and/or mb12 (with methylfolate) makes no additional difference. Nobody at all appears to get to b12 sufficiency on hydroxyb12 alone of this ill population at least. There are differring degrees of b12 starvation on the same dose for various people.



or that the mb12 was causing an interaction with perhaps mercury binding or another unknown factor or that I was detoxing to heavy?

Since your reactions are very similar to those who recover if they keep taking the active b12s plus cofactors it means that you are having startup symptoms. Everything affected at startup are usually the things that heal soonest and most completely.

If I did have the same reaction from hydroxy b12 as I did with the mb12 would that then mean?

Look for the choruses of angels hovering around. Somehow your body converts so much hb12 to mb12 and adb12 that you have an abundance of unbound active cobalamins.

However, one must remember that some people have such bad reactions to inactive cobalamins that the negative reactions stir things upin a similar way to the active but that they then come down in the direction of worse rather than better.

Good luck.

 

[xlynx]

Hi Xlynx,

When does this happen? Does it happen within 15 minutes of starting a sublingual? Or 1 hour or two hours? Or after several days of taking it daily or after a month? Is it dose related? Does it happen faster if you take more?

Certainly "light headed", dizzy, differently aware, emotional changes, emotional volitility are things that can occur from the first day and extend for some months. Mb12 affects directly many things in the nerves at all levels, peripheral and central, including transmission speeds and changes hormones and neural transmitters. These things can all be found in research that has looked for such. Generally around 3 months a different set of characteristics appears as emotions become more volitile, personality changes, especially if there were personaility changes going into the deficiency, memory improvement, processing of built up unprocessed emotional items from years of shutdown. How things are perceived is directly affected.

For 20 years I was irritable and had terrible memory problems, cognitive problems, personality change (Mr Hyde) and all that. After nearly 7 years, Dr Jeckyl is back, memory is improved and as good or better than most and mostly restored, cognitive functioning is back and the backlog of emotional processing is cleared. Everybody that has had a lot of changes going in has had a lot of these effects coming out. These effects appear to reflect the amount of damage already done.

Generally I have observed that the worse the changes and the longer a person has been ill, the larger and more pronounced are the changes produced by mb12. After the stormy period things improve and the person emerges with many changes. This can also happen following each time some cofactor is added that increases or changes the effectiveness of mb12, such as methylfolate, l-carnitine, zinc, adb12, SAM-e.

What I do know is that many people who have reported similar things in the first months to a year or so have found that it clears and that they have had a lot of healing when it is gotten through. I would offer the possibility that everything you are experiencing is due to changes that will be beneficial when they are done. It could be due to all sorts of things because mb12 does affect immune function, neurolgy, metabolism, hormones and a whole lot else. I was under a doctors care as I went through all of it, an internist, but aside from tests each month he mostly watched. He had me increase potassium at one point. He was very interested to find that after 9-12 months I was able to discontinue in a controled fashion many of the medications I had previouly found necessary to get through the day; valium, lorazapam, dilantin, compazine suppositories, Albuterol, provigil, allowing me not to fall alseep at dinner etc also acted as an antidepressant, the only one that worked.


For instance, methylb12, SAM-e, methylfolate have all been shown to decrease depression. It is my impression that the first one taken has the most effect on depression, the second thing taken has the next most effect and so on. So for me methylfolate, the last critical factor added, made an incremental change, but only on a few things that were unaffected by the mb12/SAM-e/Carnitine/adb12 etc.

I'm not sure what you are experiencing.

Good luck.

Hi Freddd,

Thank you for spending so much time on the replies to me.

The dizziness usually comes on within 15 minutes of taking the mb12 sublingual and lasts for 2 days even if I dont take any more. I experience more frequent palpitations / arrythmias, OI, swelling in glands under throat. The first month on the B12 I experienced tingling and burning sensations in my hands and feet (the kind you get when you go from cold to hot very quickly) which have finally passed and so I took that as a positive sign and a step forward. Just before I stopped on the second month I had 7 days terrible arrythmias and the most extreme dizziness I have ever experienced since becoming ill. I had to stop

I have only been ill with cfs for around 1 year although the dizzy spells and fatigue had started 1 year before.

I feel positive as since stopping the b12 I have bounced back to my basline within 5 days and appear to be stable. I think that I have come out the 2 month period with some improvments but it has been the hardest 2 months since becoming ill.

I am really interested in this protocol as nothing causes such an effect on me as the mb12 does, I am just finding it difficult to accept that I have to go so badly backwards to go forwards and am concerned I might just be hindering myself.

When you were taking the mb12 did you see any improvments in the first few months to keep yourself going? The problem I have got is I dont seems to show any improvments whilst I am on it, it is just as hard if not worse 2 months in.

Sorry if I am repeating myself I am just caught in the dilemma that is cfs :Retro smile:

Thank you,
Jerry