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B-12 - The Hidden Story

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Cort, Jul 26, 2009.

  1. Cort

    Cort Phoenix Rising Founder

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    I moved Freddd's spectacular post on B-12 from the story section to here in order to focus on it more fully. Many, many people try B12 for ME/CFS but few are cured. Freddd was actually cured when he stumbled upon the right type of B12 for him. This sparked an extensive examination of why one brand of B12 could have such strikingly different results than another.

    He started in on why B12 doesn't always produce good results in ME/CFS.

    Reasons B12 doesn't work for a person

    • They take active b12 as an oral tablet reducing absorbtion to below 1%. A 1000mcg active b12 oral tablet might bind as much as 10mcg of b12. Again the b12 has to be squeezed through a keyhole that limits the amount and is subject to binding problems in the person whether genetic or acquired.
    • They take an inactive b12, either cyanob12 or hydroxyb12. The research “validating” their use was primarily for reducing blood cell size in Pernicious Anemia, keeping the serum b12 level over 300pg/ml at the end of the period between injections. They make a statistically significant effect that can be seen in lab tests in a significant percentage of people compared to placebo. They do not heal most damage done by active b12 deficiencies and have little or no effect on the vast majority of symptoms. They may even block active b12 from receptor sites hindering the effects of real b12. They both cause a keyhole effect of having only a very limited amount (estimated at 10mcg/day) that can actually be bound and converted to active forms. They in no way increase the level of unbound active cobalamins which appear required for most healing.

      They do nothing beneficial in a substantial percentage of people (20-40%) while giving the illusion that the problem is being treated and if it doesn’t work, oh well, that’s the accepted therapy. There is no “dose proportionate” healing with these inactive b12s because it all has to go through this keyhole.
    • Some people are totally incapable of converting these to active forms because they lack the enzyme.
    • They take a sublingual tablet of active b12 and chew it or slurp it down quickly reducing absorbtionback to that same 1% and limited to binding capacity. With sublingual tablets absorbtion is proportionate to time in contact with tissues. I performed a series of absorbtion tests comparing sublingual absorbtion to injection via hypersensitive response and urine colorimetry. (EDITOR - let your sublingual B-12 dissolve in your mouth!)
    • Wrong Brand - Of the many brands of sublingual methylb12 only some are very effective. Some are completely ineffective and some have a little effect.
    • For injectable methylb12, if it is exposed to too much light (very little light actually is too much) it breaks down. Broken down methylb12 is hydroxyb12. It doesn’t work at healing brain/cord problems of those who have a presumed low CSF cobalamin level. That requires a flood of unbound methylb12 and adenosylb12 (2 separate deficiencies) that can enter by diffusion. Adenosyl12from sublinguals can ride along with injected methylb12.
    • They don’t take BOTH active b12s.
    • They don’t take enough active b12s for the purpose, espcially amounts needed to penetrate CSF by diffusion.
    • Lack of methylfolate.
    • Lack of other critical cofactors.
    • Lack of basic cofactors.
    • Taking glutathione or glutathione generating cofactors that induce an active b12 deficiency.
    So why is this the case? First, most people consider b12 deficiency to be a unitary thing. it isn't. There are 4 distinct and different b12 deficiencies each with it's own set of characteristics, and a person can have any combination of the 4. In addition is the definition of "deficiency" itself.

    In CFS/ME/FMS it has been shown that people in some studies had a specific kind of b12 deficiency, they had a cobalamin deficiency in the cerebral spinal fluid, the same as found in Alzheimer's. As it was "cobalamin" specified, there is no definition as to whether it is methylb12 deficiency, adenosylb12 deficiency or some combination of both. Each type of active b12 has it's own deficiency symptoms. The results of shutting down the neuronal mitochondria are different from loosing myelin or slowing down impulses or lacking a wide variety of neural transmitters or who knows what other effects. Unless a CSF draw is done, there is no way to detect these deficiencies. There are no standards of what is "deficient" even if a draw is done. Pragmatically these deficiencies can both be detected and differentiated. For a variety of reasons I won't go into now, I could make a case for ME being a CSF deficiency of largely methylb12 specifically for instance.

    It is not known what mechanism reduces coblamins in CSF to significantly lower levels compared to blood serum levels, in some people, from 50% to 75% lower compared to various control groups in different studies. As all 3 of my children have all the same problems I do chances appear good that it is genetic. Producing healing in this sector is sometimes the most challanging depending upon the other, mostly genetic, challenges a person has.

    Basic Challanges, some causes unknown

    • Can't absorb b12 for a wide variety of reasons including IF insufficiency (Pernicious Anemia) of either genetic or autoimmune causality.
    • Can't bind b12s for transport
    • Genetic Challanges
    • Decreased CSF cobalamin levels - hypothetical cause, confirmed problem
    • Lacking Enzyme to convert methylb12 to adenosylb12 - confimed, named cobalamin letter disease
    • Lacking Enzyme to convert adenosylb12 to methylb12 - confimed, named cobalamin letter disease
    • Lacking Enzyme to convert cyanocobalamin to methylb12 or adenosylb12 - confimed, named cobalamin letter disease
    • Lacking Enzyme to convert hydroxycobalamin to methylb12 or adenosylb12 - confimed, named cobalamin letter disease
    • Lacking Enzyme to convert glutathionylcobalamin to methylb12 or adenosylb12 - hypothetical cause, some evidence for problem
    • Lacking enough enzyme(s) to convert folic acid to sufficient methylfolate, - confirmed cause

    Each of those can be overcome. On top of the genetic reasons, the methylb12 generated by bacteria is not all the same and some bacteria breeds may generate superior methylb12. This is totally unexplored but may account for some brand differences.

    Of 10 brands of methylb12 systematically tested, 2 rated 5 stars with 5 hypersensitive testers. They were Enzymatic Therapy 1mg, and Jarrow Formulas 1 mg and 5mg. In addition Country Life Dibencozide
    (adenosylb12) also rated 5 stars. One brand of 5mg methylb12 rated ZERO stars, completely ineffective in all testers. The other 7 brands rated 1-3 stars.

    The sublingual b12s must be retained under the upper lip or tongue for 45 minutes to two hours for effectiveness with verified absorbtion ranging from 15% to 25% with urine colorimetry and by effect.

    Solgar Metafolin (methylfolate) is one of two brands available and is superior to folic acid in every way.

    Jody, I spent more of the years learning what didn't work than what did. I had some serendipidous events and some outright incredible luck and some terrible setbacks. I don't do things by halves. I personally appear to lack all of those enzymes for interconversion of forms of b12 and folic acid for instance and had all four b12 deficiencies. When I find something that works 5% of the time I find out why it doesn't work 100% of the time. That's engineering. Because my body is hypersensitive to these changes it's very much like debugging software and I can know sometimes in hours or less what takes others weeks or months to find out. Sometimes I'm just too bullheaded to get the message and keep on past all reason until it is clear. The information I am presenting here is a distillation of decades of experience and 6 years of active experimentation on myself and children. And I always do much reading to find why I should try some things or why they worked/didn't work afterwards.


    End of first part of explanation. More to come.
     
  2. Cort

    Cort Phoenix Rising Founder

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    B12 Treatment Plan

    FREDDD on B-12 Treatment

    I have divided up the vitamins and supplements in several categories. When brands are mentioned, they are essential as we have performed effectiveness tests and some brands don't work at all, a few work very well and most are mediocre. Some products are unique. These are for trying to maximize the probability of healing.

    Absolutely critical minimums for basic healing.

    • Jarrow Formulas 5mg Methyl B12, under upper lip or tongue for at least 45 minutes for best effectiveness
    • Country Life Dibencozide (adenosylb12) 3mg under upper lip or tongue for at least 45 minutes for best effectiveness
    • Solgar Metafolin 800mcg
    • Jarrow B-Right b-complex, 1 capsule twice a day
    • Potassium, your choice of brand and form - this is insurance against hypokalemia triggered by sudden healing and potentially fatal - if you have blood tests, potassium is usually checked, midrange, around 4.5 is good. Some people will have problems at bottom of "normal" range, 3.5-4.0 as I do.
    • Omega3 fishoils - essential for myelin sheathing for the nerves, many brands will do, 2-6+ capsules per day, I buy it at Costco, house brand. This is available in many supermarkets.
    Essential, usually needs supplementing

    • Zinc - 50 mg
    • Calcium/magnesium supplement
    • D - 3000-5000 IU total
    • A&D from fish oil, 10,000-(400-800-1000) Vitamin A should be 10,000, D might be any of 3 numbers with additional D to be taken
    • Vitamin E, NOW Foods Gamma E complex
    • Vitamin C – 4000+mg/day

    Possibly Critical Showstopper Cofactors - add after initial stages, any number of these in any combination may be required for maximum effectiveness or in some cases to work at all.

    • SAM-e - 200-400mg/day, makes methylb12 more effective, possibly much more effective, increases energy, improves mood
    • TMG - enhances SAM-e, methylb12, l-carnitine
    • L-carnitine fumarate (acetyl might work better for some), works with adenosylb12, lack can completely prevent effectiveness of adenosylb12, increases energy, aerobic endurance, improves mood
    • Alpha Lipoic Acid - enhances l-carnitine and adenosylb12
    • D-Ribose - enhances adenosylb12, l-carnitine, alpha lipoic acid, improves exercise recovery and energy

    Additional possibly helpful cofactors

    • Selenium
    • Lecithin
    • Chromium GTF
    • many other supplements

    THINGS TO AVOID

    Glutathione and glutathione precursors such as NAC and glutamine, undenatured whey. The glutathione induces immediate active b12 deficiencies, apparently by converting active methylb12 to inactive glutathionylb12 and rapidly excreting it.

    DEEP NEUROLOGICAL HEALING

    The most frequent neurological problems are peripheral neuropathies, often characteristic in stacking-glove distribution. Sublingual methylb12 and adenosylb12 appear quite satisfactory in healing these in a sizable percentage of the time. There exists a class of more severe neurological damage. This is sometimes identified as subacute combined degeneration and takes place in the brain and spinal cord. This can occur in people severely deprived of active b12s by diet or lack of absorbtion by other reasons.

    Another hypothetical cause may occur in people who for unknown reasons have a depressed Cerebral Spinal Fluid cobalamin level compared to their blood serum levels. In addition there may be mood and personality changes, hallucinations, sensory changes, psychosis and an abundance of neuropsychiatric changes. Some of these changes can be corrected with sublingual active b12s but some require much higher levels of active b12s than are usually achieved with sublingual tablets. In these situations usually only injections will help.

    B12 INJECTIONS

    The usual kinds of b12 injections, cyanocobalamin and hydroxycobalamin, are virtually always ineffective on any schedule. The once a month schedule for cyanob12 and the once each three months schedule for hydroxyb12 is useless as well. Daily sublingual active b12s are far superior to these in every way. These occasional injections were developed as a means to prevent people with pernicious anemia from dying. They do not promote neurological healing in any significant way.

    In order to promote neurological healing methylb12 injections of larger than usual size and greater than usual frequency must be used. My own experience is given below and corresponds with the ZONES defined on another posting. All injections are subcutaneous as that produces a slower diffusion into the blood maintaining a steadier serum peak.

    1. Single or multiple injections per day to 5mg methylb12, each injection. ZONE 2, fully equivalent to sublingual tablets, did not stop continued neurological deterioration and progressive numbing of feet of 15 years duration.
    2. Single 7.5mg methylb12 injection per day stopped the progressive numbing of feet of 15 years duration.
    3. Two 7.5mg methylb12 injections per day caused some small reversal of numbing of feet and of neuropsychiatric symptoms.
    4. Four 7.5mg methylb12 injections per day have caused substantial sustained reversal of numbing in feet and of neuropsychiatric symptoms.
     
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  3. Cort

    Cort Phoenix Rising Founder

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    My Case

    I've tried B12 injections twice with poor results; in fact B12 is one of the very few treatments I've tried that I've had negative results from the get-go with. It made me spacey, nauseous, etc.

    One was from Dr. Cheney - that I had to mix two solutions together - and one was in Dr. Holtorf's office. Not sure what kind unfortunately.

    Any ideas?
     
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  4. Tony

    Tony Still working on it all..

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    I had a similar experience with Hydroxy B12. The first injection left me even more exhausted for 3 days. The injection the second week gave no reaction. At week 3 the injection cleared my head a bit.

    Into week four I was injecting twice per week and my head really cleared. It was great! I had my brain back for hours at a time...:) I kept injecting twice per week for 2 weeks, then 3 times per week for 2 weeks, 4 times per week for 2 weeks. (My doc suggested this approach.)

    At about 3 months it was every day, but I couldn't sustain it. It was dragging me down physically. So I backed off to twice per week which I could handle. I learned later that it was probably dragging out toxins like nitric oxide too fast for me to handle.
    My doc suggested folic acid 5 mg and Vitamin E 1000 iu per day. Since I've been doing that I can handle one injection per day and it's good!

    I wouldn't be without it. 5 stars for mine...:)

    Some people can only tolerate a very small amount, like 10% of what I use. Others use a lot more than me. So it's best to start low and go slow IMHO.
     
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  5. jenbooks

    jenbooks Guest

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    IV glutathione has been crucial for me so I don't necessarily think glutathione is bad for those with lyme or CFS. It gives energy, boosts mood, and dampens free-radical induced oxidation and inflammation. Wheezing improves, so do other symptoms. Lasts only a week or so though.

    I'm interested in experimenting with the B12s now.
     
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  6. Tony

    Tony Still working on it all..

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    B12 dose

    I inject 0.1ml of hydroxocobalamin B12 (10mg/ML) each day. This is equivalent of the "Neo-B12" hydroxy available here over the counter.
     
  7. Cort

    Cort Phoenix Rising Founder

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    Honestly that kind of sucks to hear that if I'd just kept on I might have turned around on B12. I did try it twice with Cheney though. Still its something to keep in mind. Thanks for the illuminating story.
     
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  8. Frickly

    Frickly Senior Member

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    Starting B12 again

    I am just starting my third attempt at B12 supplementation. It does give me a very nervous, jittery feeling that can be so difficult to deal with. My last attempt left me naseus and dizzy but I am unsure if this was due to the b12 or running out of antibiotics. It did go away when I stopped all supplements because of feeling so ill. I did not realize it was the B12 but now am sure this is the cause as it goes away when I stop. I just started again today but am adding charcoal at night to see if this helps.
     
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  9. R**

    R** Senior Member

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    Well, I'm happy to hear a hydroxy success story.

    I am confused. I have run the yasko tests and started hydroxy. Was on adenosyl and methyl....

    I am COMT++,++, and COMT+s are supposed to have problems with methyl groups. Sheesh. So confusing.


    Glutathione is a sulfur. So.. Im not supposed to have that either.. too many sulfur groups interfere with something I would now have to look up.

    The point is to get the methylation cycle so glutathione can be naturally produced and too much sulfur can backfire that process.. ??

    Any thoughts on all that?

    Also where do you get cheaper than 35$ a shot shots? Can this be ordered somewhere. The clinic I have started to go to charges 35 a shot and recommends two a week..
     
  10. JanisB

    JanisB Senior Member

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    You can learn to do your own B12 shots. Many on the CFS_Yasko forum do. The cost for a 1 ml vial of B12 at whatever concentration you need is between $1.50 and $2.90, plus the shipping. Syringes cost about 25 cents each at a pharmacy. You do the math.

    I've made some gains on hydroxoB12 as part of the Yasko protocol, but I am wary of getting too much cobalamin to detox and don't take huge amounts.
     
  11. Tony

    Tony Still working on it all..

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    I'm not sure that injecting hydroxyB12 turns many around?... but it helps me and several others I know.
    I have a better quality of life and I only got onto it in March 08. It's also taken some tuning along the way and the benefit is at a plateau now. I wish I'd known about it earlier...still, it's good now and that's what counts!

    I wish I was in the US for the price though...my 5ml vial costs AU$70 (about US$60!)
     
  12. This is interesting reading. I've tried B12 twice so far...once via IM injection and once via sublingual tab. The results were less than spectacular.

    When I received the IM injection, I seemed to feel fine at first and then I noticed that my left eye was starting to itch. I looked in the mirror and my lower eyelid was starting to swell up. It appears that I had an allergy to something in that injection...probably one of the preservatives, I'd guess.

    From there I tried a sublingual form that I picked up at a GNC. This time, I didn't notice any allergic reactions, but I did feel like I was in outerspace for the next day or two. I got this really weird 'brain fog' type of sensation...it was really uncomfortable, but not that unique to me. I get similar symptoms from a variety of different vitamin supplements. It's unbearable though because I can't focus or think straight and just having CFS alone makes it hard enough to do those things now...don't need anymore help in that area, so I stopped it abruptly and never tried it again.

    This thread has me thinking, though. I may just give it one more shot with one of the brand names mentioned here.
     
  13. Michael Dessin

    Michael Dessin Senior Member

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    Methyl B-12

    Methyl B-12 can make folks with ME extremely sick, seen it many times, including myself. The advantage of methyl form it can bypass a lot of our traditional networks in processing B-12. So on the other hand, there is a subgroup of patients who see significant results. USUALLY those who have been ill less than 5 years.

    Autistic kids the same.

    Mike
     
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  14. Lisa

    Lisa Senior Member

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    Jeremy and I tried adding in the b-12s in Freddd's list in early June. The first week we felt better - but much more cloudy every time the sublingual was dissolving. You could feel the confusion cloud descending with in 30 minutes and then leaving again as the lozenge grew really small and then gone. Had some very promising sharpening of vision and a few other changes that first week.

    Then without us being able to tell it was going on we didn't get fully unclouded after the lozenges. Could hardly talk at all some days and life slowed down dramatically for us. About a week ago I stopped listening to my left brain saying that we just had to push through it and started listening to my right brain saying it was time to back way down on them. Thank goodness. Every day regardless of if the lozenge had been used yet or not, had been worse then the day before and was as bad or worse than we had ever been.

    I'm not sure exactly how many days we have been taking about 30% of what we were but I would guess 9 days now. The last few days we have both been coming out of our haze a bit and are starting to get back a small bit of our energy. With the clearer head (comparatively) I am going to see if we keep improving. If we don't come near where we had been before starting them then at some point I will be having us lower the dosage even more.

    I strongly suspect it has to do with the level of toxins dumped into us either from just the B-12's or possibly their kick start of the methylation cycle. Next I will lower the methyl-folate if we seem to still be having trouble in a few weeks but don't want to change too many things too fast as long as we are slowly feeling better.

    Lisa :)
     
  15. R**

    R** Senior Member

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    Thank you, Janis.

    Where do you I get this? Doctor ordered? I doubt the clinic that is trying to sell me shots for 35% a whack is going to order for me. :-( I can ask, though.

    Robin

     
  16. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Not Janis....

    But I saw your post and know the answer. Key Phamacy in Washington state (they supply Dr. Martin Pall's patients) is very up in compounded B12 and will prepare it in whatever dilution a doc orders, and yes, it requires a prescription. Wellness Pharmacy in Birmingham is another good source. I got my first vial from Key and then since have used a local compounding pharmacy.

    I don't think most people find it hard to get the script from docs as many, many patients self-inject. I do too with no problems except that momentary visceral rebellion against intentionally stabbing yourself!:eek: But it doesn't hurt if you do it correctly.

    Some people give them IM but my doc and others prefer subCu as it then is released slowly from the little bubble of B 12 that is injected just under the skin. If you do it subCu, I find that I need to push it in slowly as making that bubble of B12 right under the skin can hurt if you push it in fast.

    Sushi
     
  17. Freddd

    Freddd Senior Member

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    Hi Cort,

    It would help to know exactly what you received. The other helpful thing would be to know exactly what all your reactions were. These things follow certain patterns. Even a single one of the 5 star sublinguals can cause a knock your socks off reaction for a day. This is especially true for folks who have been taking cyanob12 and basically have exhausted their methylation capacity. Much of the same effect could be had from SAM-e or methylfolate. As most people do convert mb12 to adb12 to some degree there is also a rapid effect as adb12 starts populating the mitochondria. I'm working on a detailed titration schedule to try to alleviate some of the startup symptoms which I'll post soon. One of the things that happens is that the nervous system starts working better very quickly. This can make all existing symtoms very much more intense. It is also part of the banishment of brainfog. If a person has difficulty with getting adb12 and/or mb12 into the CSF and difficulty keeping it there. They tend to have a few minutes or hours of clarity and then redescent into fog. This appears to be due to the very short serum halflife of unbound b12s, so they only get a peek out of the fog near serum peak, like the fog of Salt Lake temperature inversions in the winter and sunshine on top of a hill and fog below in the valley.
     
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  18. Freddd

    Freddd Senior Member

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    Hi Sushi,

    I agree completely. Subcutaneous is much superior. An IM injection clears into the blood in 30 minutes. The kidneys rapidly remove the unbound b12 at an initial rate of a 30 minute serum halflife dropping to about 4 hours after 12 hours. An SC injection has a much slow absorbtion, for me by effect the main part lasting 4-6 hours and trailing off for another 12-24 hours. I use 20mg/ml solution from University Pharmacy in SLC at about a cost of under 50 cents per mg. A prescription is required and they ship in styrofoam with icepack. I wrap my vials in foil upon receipt and never unwrap them. I use the 31 gauge short (5/16th inch) insulin syringes marked in units allowing that each unit is 200mcg. I inject 37.5 units at a time (0.375ml) for 7.5mg. I do this 4 times a day as it is what is required to reverse the neurological deterioration. I'd be in a wheelchair now without it. With 4 SC injections per day, or maybe 3 of 10mg, I am able to maintain a a high constant serum level and CSF level which is obvious by effect. The SC allows the consistant level. Let the alcohol dry before injecting to avoid a sting.
     
  19. Freddd

    Freddd Senior Member

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    Hi Chronicallyfatigued,

    I will offer a couple of ideas that could help. Cofactors are needed, in fact critical to effectiveness. With CFS starting with adenosylb12 might work better. It goes directly to the mitochondria. Starting up the neurology without starting the mitochondria for energy causes a shift in symptoms and different set of problems. Also, there is inevitably much startup reaction with mb12 as it affects 600 or so things at once. I'm preparing a titration schedule that may help ease the startup. Startup can go on indefinitely until enough is eventually taken to reach an effective equilibrium and can start up again each time an effective cofactor is added. It's any of these very symptoms that indicate that it is working. Having corresponded with hundreds during startup, some have a rocker startup than others and this is often due to missing cofactors. Good luck.
     
  20. Freddd

    Freddd Senior Member

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    Hi Frickly,

    The nervous jittery feeling is very possibly mb12 startup. Let me explain with an analogy. For years our nervous systems have been out of gas. The output volume control is turned all the way up because the input is almost totally lacking and it's trying to do it's job. When it gets a little active b12 suddenly the input level turns way up and with the output volume turned all the way up the system is over driven. It will come down and adjust over a relatively short period. There are a couple of possible ways to deal with this that will be in my soon to post titration methods. The point is this would not be happening if you were not drasitically short on mb12. People who have normal levels and no deficiency have no reaction at all to any amount of mb12 or adb12; none at all. As amazing as that may seem to those who have dramatic and unpleasant reactions, it all comes from deficiencies. The more severe the multiple deficiencies, the more extreme the reactions. It is this very reaction that leads directly to normal energy. Good luck.
     
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