The Real ME: A Stock Photography Resource for the Media
We’ve all seen them in the news stories about ME/CFS: the guy in a suit at the office, yawning; the beautiful woman sitting at her desk with her immaculate make-up and elegantly coiffed hair, hand to her head and looking slightly pained.
Discuss the article on the Forums.


Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Freddd, Feb 7, 2013.

  1. Linda828


    This was extremely helpful. I increased the potassium gluconate yesterday to about 3 grams as an experiment. This morning I woke up with my legs not aching for the first time since starting B12 injections. On general principles, I was starting to supplement with 1 gram of potassium a day, but that was not enough. I never recognized my symptoms in the list of potassium deficiency symptoms so totally missed the obvious. Thanks for making it so clear. This is a huge piece of the puzzle for me.

    The other symptom that may be due to potassium is brain fog. To me it is a sense of inflammation and pressure in the brain that causes an inability to focus. That is the symptom that I get when I react badly to a supplement. The last ones were Vitamin D and magnesium. It was very interesting to read Fredd say somewhere in this thread that those were some of the common supplements to begin start up reactions for those who don’t have start up with the methyl products. Now I’m experimenting to see if potassium eradicates the brain symptoms. My first impression is that it does.

    How high is it recommend to supplement with potassium before cutting down on methyl products? Doesn't potassium inhibit B12? Does potassium only inhibit absorption of B12 in the gut or does it also affect sublingual and injected B12 absorption?

    Freddd, I was reading back over your first post in response to my questions about the cobalmin lettered diseases. I think in my last post asking about the distribution by diffusion I asked something you already answered back then. In effect you said that this is not the level at which you are concerned with. It is the pragmatics of what happens in practice that you are working out. So I’m sorry to have reiterated something you already addressed. Still, if anyone has any knowledge about the mechanisms of how the Methyl and Adenysol B12 could be distributed by diffusion into cells, I’d really be interested.

  2. Freddd

    Freddd Senior Member

    Salt Lake City
    This is a summary of the informal studies I have done in the last 11 years to solve my problems and come up with the structure as I have been explaining. Everything started with 9 months of saturation reading of essentially all available papers on internet, local libraries and papers sent to me. This is not complete as there are some more recent ones and some of this material is not as recent as some of the individually posted subsections. I am including these as they are. This whole section needs updating to most currwent forms and terminology. I'm trying to standardize terminology on MeCbl and AdoCbl for intance, and l-methylfolate unless I mean Metafolin specifically in terms of trials, as there are now other brands available. So if you compare this to some of the items extracted and updated, the most recent versions carry newer version dates. Constant revision is underway. As with the movie producer who said "movies are never done, they escape" indicates, improvments are always possible.


    1. N=1000 symptoms questionnaire with < 2 hour response to mb12, adb12 and mb12 & adb12.

    2. Mb12 urine colorimetry, 1-10mg sc injection series, 10-25mg series, 10-60mg series. 1-100mg sublingual series, determination of percentage of sublingual absorption. Further the effects of each of these for cofactors on cobalamin excretion in urine is observed and measured.

    a. Folic acid

    b. Folinic acid and vegetable extracted folate

    c. Methylfolate

    d. Glutathione

    3. N=5 mb12 hypersensitives, 10 brand comparison testing.

    4. N=10 glutathione/precursors trial

    5. Titration trials, balance of methylfolate, adb12, mb12, potassium

    6. Light exposure required to ruin mb12

    7. Overcoming Types 1, 2 and 3 paradoxical folate deficiency/insufficiency titration trials

    8. Determination of CNS threshold effectiveness dose for adb12 and mb12 independently, both sublingually and injected SC.

    9. Five batch injectable mb12 comparison testing against 5 star batch of injectable MeCbl.

    10. Composite international list of symptoms

    11. Distinguishing the four specific forms of b12 deficiency and pharmacokinetic modeling.

    12. Family tree of methylfolate, adb12 and mb12 deficiency diseases

    13. Three types CSF/CNS cobalamin deficiencies

    14. Mb12, ADb12 and Methylfolate Insufficiency vs Deficiency

    15. Metanx, Deplin and Cerefolin-NAC and side effects.

    16. CSF/CNS penetrating doses of adb12 and mb12 for those with low CSF cobalamin levels.

    17. ZONES of healing by type and quantities of cobalamin

    18. The reasons why b12 and folate therapies fail

    1 - I had to find out whether my rapid strong response was usual or not before deciding what to do next; and to find out what mattered for a screening questionnaire for health screening of certain sorts. I questioned approximately 1000 people selected by running into them socially in normally healthy circumstances with no selection for health, age or gender. Approximately half the people had a multitude of symptoms on a list that has become very familiar. Given a single dose of either of the two 5 star mecbl tablets identified and/or an adb12 tablet and held under the upper lip for 45+ minutes, approximately 80% of the people with symptoms responded very noticeably within 2 hours, almost all within 1 hour. About 15% of those who claimed no symptoms responded and then said “I had forgotten about those since my doc told me they were nonspecific and didn’t matter years ago.” Later with follow-up, most who have symptoms and don’t respond need another critical item to respond, especially Methylfolate and/or l–carnitine fumarate. People genuinely without symptoms have no noticeable effect at all from these supplements. The most common response is “energized”, brighter mood and perceptions are all brighter. A person who gets to equilibrium with sufficient mb12 and adb12 have no noticeable immediate response to having taken any quantity. Only those with some level of insufficiency or deficiency have any noticeable effect.

    2 – I did the colorimetry (using magenta, yellow and cyan subtractive color printing filters) over a number of years and still pay attention as increased b12 in my urine is my first sign of going into folate insufficiency. Basically what I found was that with folic acid the threshold of visibility is 2.4mg SC, with Metafolin 4.4mg SC, with glutathione the first time was terribly red, and stayed terribly red the whole trial period, like a 100mg injection without any injection prior. I also found that 50mg of sublingual held for 45 minutes to 2 hours or longer of the two 5 star mb12 and an effective adb12 absorb to be excreted at a rate comparable to 7.5mg to 12.5mg sc injection, 15-25% with an extreme of 10% to 33%.

    3- When the one brand I had told people about went out of stock nationally for several months, I had to find another brand as I regressed a full months worth of progress in a week on another brand, I was desperate. So I then recruited 4 others who had a strong response to the first brand and bought 10 brands which we all tried. One more was excellent, 1 was so bad it was nothing at all and the others were all poor. All 5 of us were in 100% agreement on the two 5 star and one zero star brands. Just precisely how bad the others were had minor variation. Later I tested another 20 brands or so and didn’t find any more 5 star brands. This was repeated over and over by many people who have at best nominated 2 brands for perhaps 4 star quality in more than 9 years.

    4 - HOW TO INDUCE SUBACUTE COMBINED DEGENERATION and enlarged MCV in humans in 3 months or less.

    Causing SCD and macrocytic anemia was NEVER our intention, our intention was to induce heakth benefits from glutathione or precursors as claimed these days amongst certain practitioners. This is just how it turned out, 180 degrees from what we expected.

    Individual results will vary but in an N=10 trial, 100% of subjects had the results to varying degrees, perhaps as they used several different precursor combos or infusions. The subjects were all successful with adb12, mb12 and Metafolin. Those not in this group that had never relieved the deficiency symptoms claimed pain relief from the glutathione as their nerves were damaged further into numbness.

    Method 1 - feed subjects 1 gram of l-glutamine and 600mg of time release NAC twice a day for duration (or frequent glutathione infusions, or NAC or whey in some). In 3 hours after first dose most of available b12 in the body will be flushed out in the urine. Then within the next few hours methylfolate is expelled from the cells via the "methyl trap". Widespread body, muscle and joint, inflammation and pain start within hours and gets worse by the day. This is responsive to NSAIDS generally. Folate deficiency symptoms appear the first day, mb12 deficiency symptoms in several days and adb12 deficiency symptoms - 3 months or so.

    Over the next days and weeks, CPR heads for the roof. Hypersensitivity of all sorts starts, MCS, hyper-immune response, hypersensitivity in nerves, etc. In 3 days angular cheilitis starts up in those who are prone to it. In 2 more days IBS starts. At about the same time acne type lesions start up on scalp and face and often infected follicles in other body areas. Oral lesions usually follow. By six weeks centrally mediated numbness and pain of feet and legs, hands, arms, shoulders etc are all spreading and worsening.

    Dr Jeckyl leaves the house and is replaced with Mr Hyde for the duration. Sleep disorders increase. In 3 months macrocytosis is obvious, MCV > 100. MS will be dramatically worsened. If the person is also extremely low on l-carnitine and/or adb12 Parkinson's like symptoms may worsen explosively. Then if l-carnitine is given the subject may go absolutely nuts and a walkthrough of the extreme FFF characteristics of the limbic system will be demonstrated in usually the same order each time, dependent upon rising or falling l-carnitine level.

    Reversal, if SCD is not allowed to go too far is multiple 15mg doses of Metafolin (Deplin) and three 50mg mb12 doses or 10mg SC injections of SUITABLE 5 star mecbl until healed for at least a year, and of adcbl the first few days. On day 3 need for potassium will increase by 2000-3000mg to avoid dramatic sudden onset of Hypokalemia symptoms when backlogged healing starts up. Also on day 3 Metafolin dosage needs increase. In about a month inflammation will be largely gone if all cofactors are present that are needed, CRP <=1.0, multitudes of pains will be fading. Only the remyelination and MCV take about 9 months to correct to the extent that they can but trail on for years as it is an ongoing equilibrium that is either getting better or worse.


    Version 1.1, 10/20/2012 pattern pragmatically correct, numbers are pragmatically correct but are based on considerable timing considerations so twice as much may be needed if dosed only twice a day.

    Generally an adb12 sublingual once a week or so of 10mg or so is sufficient for unchanging equilibrium but a few need it as often as daily. Methylb12 can be titrated from even a crumb to about 15 or 20 mg for most people for maximum rate and extent of healing. The nutrients below may need minor adjustments as rates of healing go up and down. The


    1. PFD0,3 100mcg to 20mg mixed mb12, adb12, 2400mcg methylfolate, 2000-3000mg potassium

    2. PFD 1 100mcg to 20mg mixed mb12, adb12, 7500mcg methylfolate, 2000-3000mg potassium

    3. PFD2 100mcg to 20mg mixed mb12, adb12, 15,000mcg methylfolate, 2000-3000mg potassium


    1. PFD0,3 30mg-150mg sublingual, 30mg sc injection (3x10mg), daily mixed mb12, adb12, 2400mcg methylfolate, 2000-3000mg potassium

    2. PFD1 -150mg sublingual, 30mg sc injection (3x10mg), mixed mb12, adb12, 7500mcg methylfolate, 2000-3000mg potassium

    3. PFD2 30mg-150mg sublingual, 30mg sc injection (3x10mg), daily mixed mb12, adb12, 15,000mcg methylfolate, 2000-3000mg potassium

    6 - It took no more than 10 minutes cumulatively of normal room light to damage injectable mb12 in a clear vial or 2 minutes in a clear syringe to damage the mb12 to such an extent that it was ineffective and caused acne type lesions on scalp and face in 2-3 days. This was repeated unintentionally hundreds of times. Using a deep red photographic safelight (fast ortho film) for preparing solution, drawing injection and injecting or wrapping the vial in foil full time and pre-wrapping each syringe in foil is only prevention. It’s easy enough to draw by feel with a 31 gauge 5/16 insulin syringe and works better for CNS purposed to inject subcutaneously. This has been experienced by most who inject and NOW it is explained and completely prevented.


    1 – Type 0 PFD 2400mcg Metafolin (1600-3200mcg) will support rapid healing with zero folate deficiency or insufficiency symptoms or signs

    2 – Type 1 PFD, folic acid - 7500mcg Metafolin (6000-9000) will support rapid healing with zero folate deficiency or insufficiency symptoms or signs, if folic acid is avoided as much as possible.

    3 – Type 2 PFD. Folic acid AND folinic acid - 15mg Metafolin (12,000-24,000) will support rapid healing with zero folate deficiency or insufficiency symptoms or signs if folic acid and folinic acid is avoided as much as possible. As folinic acid is in most vegetables that is difficult when eating a good diet and appears to be why a higher dose is needed..

    4 – Type 3 PFD. The sudden appearance of folate deficiency symptoms after healing startup with 100mcg+ of mb12/adb12 and a small dose of Metafolin which causes 3rd day potassium need will then require titration of Metafolin until sufficiency is reached. A small dose can start more healing than it can continue and cause onset of folate insufficiency symptoms. Titrate to full effectiveness.

    8 - In a series of injections that went from 1 to 100mg per dose, the body responded strongly starting around 100mcg with rate and quantity of healing increasing in a non-linear dose proportionality. Falloff of increase appears to be logarithmic. Body effective doses were 10mcg to about 3000mcg injected SC. Then no change until about 7.5mg SC and then a one time CNS response, repeatable daily unless maintained as 3x10mg per day, with no further apparent response to 100mg dose.

    9 - Injectable methylb12 prepared by compounding pharmacies is often ruined by too much light exposure while preparing or after. If it isn’t ruined about 1 batch in 10 appears to be 5 star, and the others lesser so. The 5 star is the only kind that heals the CNS so far in my experience when injected in sufficient quantity to force CSF entry by diffusion, an estimated 200,000 pg/ml 24/7, required in a group of diseases. I was able to accumulate half a vial per month of mb12 in the freezer. After a while I had 5 different batches to run a side by side comparison. I also had a full vial of a 6th top notch vial for comparison. One of the 5 vials was 5 star as well as the standard, but none of the rest came close. The difference is evident within 4 hours.

    10 - Each country appears to work from its own list of b12 deficiency symptoms. The list for cyanocbl using countries is different from hydroxycbl using countries. Each country has different inclusions and exclusions on the list due to cultural importance. India is the only country that has a lot of studies concerning the effects of b12 on reproduction, sex and fertility. Tantric practitioners millennia ago had come up with the “Tantric” meal for a vegetarian country. The meal contains methylb12, adenbosylb12, methylfolate, l-carnitine, omega3 oils and high quality protein. It’s effects were “magical” in a vegetarian society, and not because it was a taboo buster as thought but because such a meal can raise serum level from 100ng/ml (nonfunctional sexually, non-reproductive, unhealthy) to over 600ng/ml in a matter of hours providing functionality via a burst of ATP generation within 3 hours. In any case either b12 symptoms are a matter of culture and opinion or they were all drawing from different parts of the same universe. The Japanese list, based on the ONLY country using methylb12 as the official b12 has a far more complete list. When they are all added together and expanded for detail (ie 20 details instead of “peripheral neuropathy”) likely to evoke a response from a subject and those items specifically affected by mb12 and adb12 the list is over 400 items long. The glutathione trial allowed the distinguishing of what are the hard deficiency symptoms of folate deficiency instead of totally and blindly mixed together. For instance, the list as it now stands includes 10 different varieties of muscle pain from different deficiencies that might be all rolled into one that reveals nothing. The specific details tell all.

    11 - So, the question is asked “What is the serum halflife of b12?” Lots of researchers have asked that and there is significant publication. The problem is that the results are confusing and contradictory. That is because the question as it stands is unanswerable. The question treats “b12” as if it were a single compartment model. It isn’t. There needs to be at least 5 compartments, each with its own dynamics, to get rid of the contradictions and confusions. First there are two forms of active b12 in the body, methylb12 which is the main circulating form and is rapidly filtered out by the kidneys and adenosylb12 which gets installed in mitochondria and stays there. We have mb12 with a serum half life following injection of about 30 minutes with symptoms returning in less than 3 days and adenosylb12 with a tissue halflife of perhaps 90 days. Then we have the liver and the entero-hepatic recirculation loop with its own dynamics. Then we have the CNS/CSF which is independent of the body serum level and can have deficiencies even when the body has normal or high levels. Again we have the mb12 that largely disappears from CSF in 12 hours sufficiently for return of symptoms to start and the adb12 which has a tissue halflife of maybe 90 days. The two CSF/CNS deficiencies and the two body deficiencies can each be separately distinguished by questionnaire and demonstrated via an established method.

    I developed a time release and/or regular release blood serum simulator that can take absorption profiles of Oxycodone and Oxycontin, and all sorts of other medications and recalculate the serum level curve with adjustments for serum halflife, liver, kidney, Gut Transit Time and found some real impossibilities in some graphs which appear as if somebody applied Finagale’s Universal variable constant to get the answers the marketing department wanted. That model works on items with a constant serum halflife. That doesn’t appear to be the case with b12. The serum halflife is dependent upon the form of the cobalamin as well as the cobalamin concentration in serum. The formula for this is derivable from the curve. I developed a spreadsheet model of serum mixed cobalamins that matched the data from multiple studies at all the different time intervals used and variations on descriptions.

    By model and calculation, 10mg injected subcutaneously each eight hours works out to 1.25 mg/hr diffusion into serum for all 24 hours. My serum level of cobalamin was modeled and estimated to be in the neighborhood of 125,000 to 200,000 pg/ml. Less than 7.5mg failed to penetrate the CSF sufficiently for me.

    12 - The family tree of low CSF cobalamin could be considered the mix of the 6 main deficiencies so far identified. Research has shown, and is furthering all the time currently, that certain diseases feature CSF deficiencies of these nutrients.

    1. FMS – low CSF cobalamin – pragmatically low mb12 and adb12 in CSF AND low mb12 and adb12 in body.

    2. CFS – Low CSF cobalamin - pragmatically low mb12 and adb12 in CSF AND low mb12 and adb12 in body.

    3. MS – Low CSF cobalamin, elevated HCY (usually indicates low mb12), follows the pattern of cyclical paradoxical folate deficiency , low folate could also be cause of elevated HCY as could low p5p

    4. Subacute Combined Degeneration – Low msb12 AND low adenosylb12 by pragmatic response testing. Also low body levels of mb12 AND adb12 AND low methylfolate possibly with PFD.

    5. ALS – Low CSF cobalamin, elevated HCY, elevated MMA (usually indicates low adb12 or carnitine)

    6. Parkinson’s – Low CSF cobalamin, elevated MMA, and pragmatically low carnitine/adb12 in limbic system causing neuronal mitochondrial malfunction

    7. Supra Nuclear Palsy – low CSF cobalamin

    8. Alzheimer’s – low CSF cobalamin

    9. Autism – low CSF cobalamin

    13 - There appear to be two reasons people have low CSF/CNS cobalamin; difficult slow gain of cobalamin to CSF, rapid loss of cobalamin from CSF and then combination of slow gain AND rapid loss. In a study, in Japan, of 2.5mg intrathecal mb12 injections the duration of maintained high CSF cobalamin level with effectiveness of action ranged from under three months to more than 4 years. On the other side of things are those who require a 7.5mg or more SC injection to penetrate the CFS/CNS and it’s effectiveness may last for < 6 hours to more than a month. For those with both problems, the ranges look more like this. 7.5mg SC QID, 10mg SC TID, 15mg SC BID , and not all 3 dosing patterns work for everybody. I can only use the 7.5mg QID and 10mg TID effectively

    14 - Deficiency vs. Insufficiency - B12 and folate deficiencies manifest in very dose proportionate ways. There are no sharp cutoffs until one gets to 100% needed dose. In the list of the folate deficiency symptoms under many names, some people might have mood effects before they have IBS, some might never have angular cheilitis, but what does happen is that there are several different groupings of symptoms that tend to appear together. So in an extreme deficiency body wide inflammation would be up with lots of joint and muscle pain, MCS. Allergies and asthma come in somewhere but it can vary. So the greater the insufficiency the more symptoms and the worse the symptoms are. While any of the insufficiencies can cause the same symptoms they cause them in different groupings. So it is necessary to remove all the b12 insufficiency symptoms to expose all the remaining methylfolate insufficiency symptoms. That is how it happens in the titrations. Endless time has been wasted disagreeing as to “absolute deficiency” vs “functional deficiency” and what it means, if anything, for therapy. The idea of an absolute deficiency in either of these is ridiculous as the last symptom in the progression is paralysis of the diaphragm followed shortly by death. Everything short of that is a summation of successive insufficiencies.

    15- Metanx, Deplin and Cerefolin-NAC are variations on the theme of active vitamins. So first there is Metanx, a combination of 3mg of Metafolin, 35mg P-5-P and 2mg of methylb12 with one tablet twice a day. Metafolin is well absorbed orally and raises active folate in the blood seven times as much as folic acid at the same trial doses. As methylb12 is absorbed at about 1% if swallowed that is about 20mcg twice a day. This might after a while turn on healing but it won’t be as reliable or rapid in this as 100mcg absorbed combination of sublingual adb12 and 5-star mb12 daily and distributed throughout the body rapidly via diffusion. Metanx occasionally turns on healing as the side effects pattern shows both mild Hypokalemia and perhaps some paradoxical folate deficiency if the symptoms are looked at with the decision tree. Deplin, at 7.5 mg and 15mg once or twice a day says “Metafolin is generally well tolerated with side effects equivalent to placebo”. Basically it might worsen some of the already present symptoms while relieving others until the dose is high enough. 15 and 30mg daily were found far more effective than 7.5mg. Cerefolin-NAC is a whole different ballgame. For a lot of people the NAC triggers “NAC detox” which as another name for severe induced folate deficiency with mb12 and adb12 deficiencies to follow. Again, tracing the symptoms through the decision tree will locate that and the solution. These so-called “detox” syndromes block methylfolate at the cellular level regardless of dose taken. There is no overcoming it while the NAC and/or glutathione are taken.

    16 - This family of diseases has difficulty getting mb12 and adb12 into the CSF in sufficiency or retained in sufficiency. The Japanese found that approximate 50mg a day could cause mb12 penetration to the point of improvement. I and others have pragmatically replicated CNS response up to and including healing. With timing as a consideration we have found that the minimum threshold for CNS effectiveness is between 6 and 7.5mg SC injection, 7.5mg QID, 10mg TID OR 15mg BID generally maintains effectiveness for 24 hours daily. This is duplicated with single sublingual doses of 30-50mg depending upon absorption duration-percentage. Recently, because one brand on which I was dependent changed and no longer worked neurologically and came in 5mg doses, I had to find something that works well enough until I can line up some 5 star mb12. Based on my model indicating that a range of 125,000pg/ml to 200,000pg/ml was needed for sufficient CSF penetration AND that it had to be maintained sufficiently long to allow more healing to occur in 24 hours than deterioration, I had to find a sublingual method of 1mg only tablets but all of 5 star mb12 with no 3 star mb12 for injection to boost the concentration because the lesser amount of 5 star became too diluted. To make a long story short I was able to achieve sufficiently high serum level of 5 star mb12 with 30 1mg tablets daily to reverse once again the CNS neurological deterioration by taking it in 6-7 groups of 4-5 tablets gets the serum level high enough for 15 hours daily to be ok. This again was a titration by effect. Once a week I add 10mg of adb12 across 12 hours of absorption time. Both are needed for neurological healing. Out of that brand handled most carefully I can manage a tested 40+% absorption. I must be squeezing near 1mg/hour so I can get that 100,000pg/ml to 175,000pg/ml for 15 hours or so.

    17 – B12 ZONES – Version 3.0 10/26/2012

    This is the recent re-conceptualization taking recent knowledge into account

    I. ACTIVE TRANSPORT ONLY ZONE - Oral or injected cyanocbl or hydroxcbl, about 10mcg possible absorption via active means per meal and ends up transported by HTCII and subject to the body’s triage methods. Weakly dose proportionate up to doses of 125mcg orally, saturating the active transport system. Limited symptom effectiveness.

    II. DIFFUSION – BODY TRANSPORT ZONE - Sublingual proven effective (5 star) methylb12 and adenosylb12 500mcg (approx 100mcg absorbed) or 100mcg injection. Threshold dose for “turning on healing”. Strongly dose proportionate 1-100mcg absorbed. Moderately dose proportionate 100-3000mcg absorbed, weakly dose proportionate 3000-20,000?mcg absorbed.

    III. DIFFUSION CSF/CNS TRANSPORT ZONE – An estimated serum cobalamin level of 100,000pg/ml to 200,000pg/ml maintained 24/7. 7.5mg QID, 10mg TID or 15mg BID of 5 star mb12 has worked for many trying it. Threshold effect at between 6 and 7.5mg SC injection.

    IV. INTRATHECAL INJECTION 2.5MG METHYLB12– Japanese research has tried this and found effectiveness lasted 3 months to 4 years (latest report)


    Version 2.0 - 03/10/11, Version 2.1 - 05/08/11. Version 3.0 – 10/25/2012, Version 3.1 10/26/2012, Version 11/05/2012 3.2

    1) 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 10-30mcg/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 enzymes or ATP

    2) They take active b12 as an oral tablet reducing absorption 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.3. They take a sublingual tablet of active b12 and chew it or slurp it down quickly reducing absorption back to that same 1% and limited to binding capacity. With sublingual tablets absorption is proportionate to time in contact with tissues. I performed a series of absorption tests comparing sublingual absorption to injection via hypersensitive response and urine colorimetry.

    3) Of the many brands of sublingual methylb12 only some are very effective. Some are completely ineffective and some have a little effect.

    4) 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. Adenosylb12 from sublinguals can ride along with injected methylb12.

    5) They don’t take BOTH active b12s.

    6) They don’t take enough active b12s for the purpose.

    7) Lack of methylfolate

    8) Lack of sufficient Methylfolate, a dose can start more healing than the same dose can complete.

    9) Paradoxical Folate Deficiency - Folic acid is taken which can block at least 10 times as much methylfolate from being active inducing folate deficiency even if methylfolate is also taken. These induced deficiency symptoms are often called "detox" symptoms. Folinic acid is taken which can block at least 10-20 times as much methylfolate from being active inducing folate deficiency even if methylfolate is also taken. These induced deficiency symptoms are often called "detox" symptoms.

    10) Lack of l-carnitine fumarate (rarely ALCAR), the 4th of the Deadlock Quartet

    11) Lack of other critical cofactors.

    12) Lack of basic cofactors

    13) Glutathione, glutathione direct precursors, NAC and /or whey is taken causing what is often called "detox" while actually being induced folate and b12 deficiencies.

    14) Having many additional supplements and herbs of unknown interactions and effects.
  3. Freddd

    Freddd Senior Member

    Salt Lake City

    I speak specifically of MeCbl and L-methylfolate in the body and specific places they function, or not, not how they get into the body. Right now research is going on that may expand the quantity of specialized and temporary cobalamins up to 100 or more, making for seeming much more complexity. It appears however that MeCbl is the starting point for all these variants, at least according to the researchers doing this study. Many are very fragile and last only for seconds as products, by-products and end products of a multitude of reactions. Some ressearchers indicate over 600 specific biochemical reactions are affected by AdoCbl and Mecbl. Nobody knows what forms are created for instance when MeCbl neutralizes Botox or tetanus neurotoxins.
    What it comes down to is that when MeCbl (regardless of source) is low enough where and when it is needed to cause the methyl trap the symptoms that get terribly bad are folate deficiency symptoms regardless of the form of supplemented or quantity. The L-methylfolate needed for the transaction and severe folate deficiency symptoms predominate. If the transactions break because of lack of MeCbl, the symptoms are those of b12 deficiency. If the transactions break because of lack of folate exactly where needed, folate deficiency symptoms predominate. Giving a small amount of MeCbl will cause the folate deficiency symptoms to go away and the b12 deficiency symptoms increase. Then if more l-methylfolate is present and the amount of MeCbl decreases slightly, suddenly severe folate deficiency symptoms again reappear and B12 deficiency symptoms are relatively reduced. This can bounce back and forth with opposite of the expected symptoms alteranting. This is mystifying experience, a repeated experience, of me and plenty of others. My opinion is that these apparently paradoxical seeming symptoms and changes of symptoms are very understandably misunderstood and misinterpreted.

    So now, going from that understanding of the often paradoxical symptoms of the methyl trap, when this occurs while taking HyCbl, the form of folate is irrelevant, HyCbl can’t break methyl trap as more HyCbl is in the extremes dependent on the Deadlock Quartet for conversion to MeCbl and then AdoCbl. CyCbl, folic acid and folinic acid are also all dependent on the Deadlock Quartet for their successful conversion. If one follows back along the pathway of each of the conversion processes, one hits ATP. Following that back one needs some “single carbon” (CH4, methyl) transactions somewhere along the way. Those are directly dependent upon AdoCbl, L-carnitine fumarate, MeCbl and L-methylfolate. There is no escaping these 4. All 4 are mutually dependent upon each other. A sufficient lack of one cripples the others. SAM-e, the “universal methylator” is dependent upon L-methylfolate AND MeCbl. If any other forms are shown in a diagram they also have a side loop showing the conversion of inactive to active forms.

    So when “detox” symptoms happen with MeCbl AND L-methylfolate, the three most likely forms are ATP startup, paradoxical folate deficiency/insufficiency and/or low serum potassium. There appear to be other lower probability branching not yet clearly defined. What does not happen with sufficient MeCbl/AdoCbl (perhaps 250-1000mcg sublingual [perhaps 100-250mcg absorbed] held 45-120 minutes, 15-25% by thousands of iterations) combined MeCbl-AdoCbl) and sufficient L-methylfolate (perhaps 200mcg) is the methyl trap.

    The partial methylation block is not the same thing as the methyl trap. The onset of partial methylation block can be slow and insidious and creep up on one. For me that creep up started by 2 years old and got worse year by year. Methyl trap generally hits pretty heavy and doesn’t generally get better until one does what is needed to get out of it Then there is methyl trap with mitochondrial failure or something of the sort which goes progressively and then falls off a cliff. For me they appeared to happen together and appear self reinforcing. I went from skiing a week earlier to being unable to walk more than 50 feet for 6 months. The first month I sometimes crawled. I stayed in that triple whammy for almost 17 years without break. I’ve been working on this since 1978 or 79.
  4. Freddd

    Freddd Senior Member

    Salt Lake City

    Hi Xara,

    we are guinea pigs experimenting on ourselves and learning from each other.

    Folic acid, HydroxCbl and CyCbl are all experiments on all of us, the population over the last 60 years. There were NEVER and studies done to establish equivalence to the real items. Folic acid became the standard by assumption. CyCbl became the standard by assumption. HyCbl was tested against CyCbl for effectiveness. Oral forms of CyCbl and HyCbl were tested against injectable forms of the same. CyCbl FAILED all atempts to validate it against liver extract. It won the Nobel Prize and was assumed to be correct. Ten years later when the real b12s were identified without a doubt NOBODY went back and validated CyCbl against MeCbl and AdoCbl by direct comparison. If they had somebody would have been saying what I am saying in 1960.

    Absolutely. The medical doctors and research establishment have treated us (ME, CFS, FMS etc) very badly.

    Where I live doctors in regular medicine laugh when the word detox is mentioned,

    doctors in regular medicine point to psychological treatments when confronted with a patient having ME/CFS, and they are being backed by official treatment guidelines (it's the same in the UK, I've read).

    Yes, they laugh and want to give people antipsychotics to keep people quiet. You know "Go away and don't bother us. Here are some drugs to make you sessile and stupid and give you lots of side effects so you can be side tracked dealing with those. Stop complaining, we are treating you". Detox is imaginary, don't you know? Their eyes glaze over and they stop listening. I'm trying to put together a decoding of the word "detox" so the doctors can be useful. Most of the docs don't believe in "methylation” either. I had a female neurologist tell me, will sticking electrified pins into me and watching a meter, "I could diagnose you with FMS but then you would be treated badly by many doctors because you have an imaginary woman's disease". I've been through all this, for decades. It's also why there is so much movement towards practitioners who at least accept that we are, or were at the time, sick. For me it isn’t current any more. I've had the same 2 docs since 2001 and 2003, not possible when I was sick and untreated. I would end up getting kicked out for being in denial of being an alcoholic based on blood work. I couldn't drink. It made me too sick. They would rather insist that Its All In Your Head (IAIYH), alcoholic, conversion disorder and so on. They miss the boat completely.

    For instance when it comes to folinic acid (man has been eating greens for centuries, for me it's hard to believe folinic acid is capable of blocking so much of essential methylfolate), or when it comes to the difference in sensitivity when taking different amounts of methylfolate (no reaction to big amounts, symptoms when getting low amounts).

    Yes, folinic acid is a puzzler. All I can offer is pragmatically derived from myself and some others. We evolved eating veggies. I had IBS, angular cheilitis, allergies, asthma, sleep disorders, sick a lot with certain things, they are in detail on the list of symptoms in childhood, and I share those with a certain percentage of others, and all that as a child. So clearly something was up. Why I can’t use the vegetable folate well? I don’t know and have to assign to a polymorphism or something. When I first got folic acid in foods I got very much sicker. I went from missing 1/5 or 1/6 of the school year to missing 1/3 of the school year. I like vegetables, have nearly 600 sq feet of raised bed organic gardens now, larger gardens when I was younger with children and became a vegetarian, making sure of taking all my vitamins (CyCbl of course in those days). Within 2 years I had to take a sedentary job. Another 5 years and I had CFS/FMS (though totally undiagnosable in 1987, yuppie flu and all the rest of the name calling) with a total systems crash that didn’t get better for almost 17 years. Some tribes ate a lot more meat for a long time. I would expect in countries with millenia of vegetarianism that those genetic lines that can't utilize vegetable folate would be long dead.

    What I am trying to point out is the possibilitythat folinic acid has dose proportionate effectiveness curve similar to folic acid. For folic acid, small amounts are helpful for most people. As the dose increases a maximum effectiveness is reached and then effectiveness declines and goes into negative territory. So studies giving 2.5mg of folic acid find little additional effectiveness, less now that there is so much folic acid in the food supply then when there was no folic acid in the food 30-40 years ago. One of the big puzzles for folic acid is why has its effectiveness appeared to change over time and why isn’t there some kind normal dose proportionate effectiveness. Why doesn’t it work as well as it “should”.

    I did a titration series with folinic acid and a different series with some very expensive vegetable extract b-complex. At the doses of the folinic acid in both the pharmaceutical folinic acid and the natural veggie extract folate in the b-complex, 800mcg specified on the labels, they had the same reaction as folic acid for me. This was in addition to unchanged L-methylfolate in all cases. They threw me into “detox” very rapidly. The folinic/veggies “detox” took longer to wear off before being able to correct it with L-methylfolate. This was after I had come onto these boards and was surrounded by people with “detox” from taking folinic acid under whatever brand names and in whatever mixes. Folinic acid induced “detox” appears to be common here. However, I also think that these disorders we have, FMS, CFS, ME and related mystery diseases with the same universe (set) of symptoms in various mixes.

    Upon closer examination of “detox” experienced as a result of starting methylation via various choices it was clear that there was a distinctive bimodality. With folinic acid the bimodality were the temporary low potassium, Hypokalemia symptoms but not having the tissue deficiency of potassium, so call it either a functional deficiency based on system lag time in buffering the need for potassium or whatever you like. Functionally it acts like Hypokalemia and if maintained as such long enough can become a dangerous issue. Those that appear to have genuine low tissue potassium get in trouble in days because there is no potassium available to put back into serum. Waking up screaming in pain with leg spasms every night can be very convincing when potassium relieves it in 30 minutes and a few tablets at bedtime can often prevent it 100%, assuming that one is close to sufficient with ONLY temporary low serum level. It’s a trial only the person involved can do for themselves when the symptoms show up. The Hypokalemia comes around in those with successful methylation startup. The folate insufficiency is quite paradoxical and is potentially far more confusing for a number of reasons.

    So, assume HyCbl AND Folinic acid. “Detox” starts with symptoms typical of some kind of induced folate deficiency. More folinic acid changes nothing. More HyCbl changes nothing. L-methylfolate changes nothing. What does that say?

    Some of the possibilities.

    1. Methyltrap caused and HyCbl isn’t able to supply sufficient MeCbl to end Methyltrap. Dependencies – HyCbl requires methyl group AND enzyme AND ATP (requires AdoCbl, l-carnitine fumarate, functional methylation (MeCbl AND L-methylfolate AND functional ATP production)) Folinic acid requires methyl group AND enzyme AND ATP (requires AdoCbl, L-methylfolate and functional methylation (requires MeCbl AND L-methylfolate AND functional ATP production

    2. Straight out folate deficiency and HyCbl can’t supply the MeCbl to use it adequately. Dependencies – HyCbl requires methyl group AND enzyme AND ATP (requires AdoCbl, l-carnitine fumarate, functional methylation (MeCbl AND L-methylfolate AND functional ATP production)) .

    3. Paradoxical folate insufficiency with insufficient l-methylfolate delivered where it is needed Dependencies Folinic acid requires methyl group AND enzyme AND ATP (requires AdoCbl, L-methylfolate and functional methylation (requires MeCbl AND L-methylfolate AND functional ATP production)

    Another possibility is more HyCbl changes symptoms or adds symptoms. This is one of the more peculiar occurrences.

    1. HyCbl provides just enough MeCbl to get out of methyltrap. Then lack of MeCbl is most limiting feature and B12 insufficiency symptoms get a lot stronger and folate insufficiency symptoms lessen but don’t go away as ordinary folate insufficiency or paradoxical folate insufficiency take over.

    2. HyCbl provides ample MeCbl and folate insufficiency or paradoxical insufficiency predominate and there is little apparent change even though the situation has changed from blocked methylation to induced deficiency with healing started.

    A problem then with starting with HyCbl and Folinic acid is that it’s is very difficult to know what is happening when “detox” starts. There are too many contradictory possibilities available. After trying to makes adjustments, nothing changes or the changes are difficult at best to interpret. A person doesn’t know what their folate problems are at that point. After getting things started and stable, established in a healing pattern, a person can know in week long A-B trials whether the form of folate makes any difference or not TO THEM. To my thinking it is essential to know what does and doesn’t work for the person at hand. That’s a choice of course.

    All of this is observation and if there are any theories or hypotheses involved. The “methyl trap hypothesis” of the 60s, for instance, is quite well accepted, now, 50 years later. They keep refining and extending the definition. There are 257 references findable on Google Scholar that make for some interesting reading. As MeCbl and L-methylfolate functioning needs to be understood that understanding is barely started.

    This has all been arrived at via close observation of my own body and experiences and those of other volunteers. Rich supplied the identification of the methyl trap, which he indicated is misnamed, and so do I, and he suggested a more suitable name in one of his later posts. The name, methyl trap has been around about 50 years and doesn’t look like it will get changed to a better descriptive name any time soon. The name Rich suggested was something like methylfolate trap, far more descriptive.
  5. Freddd

    Freddd Senior Member

    Salt Lake City

    Hi Linda,

    I'm jumping in to clarify here becaues I think that it is important. The transcobalamin system, TC1 (hapticorin), TC2 and TC3 and the equivalent occupied with cobalamin HTC1, HTC2 and HTC3 and IF were all developed evolutionarily to extract and concentrate natural cobalamins from meat present in parts per trillion or thereabouts and similar foods, protect it from stomach acid, and later in the bloodstream from chemical assault and kidney excretion. The HTC1-IF passes the absorbed cobalamin through the intestine wall and ends up in HTC2 for transport to the cells. There are a lot of fuzzy areas and conflicting assumptions, research results and so on about this end of the system. In the 1930s and before people were dying of Pernicious Anemia. A Nobel Prize was awarded for identifying that 2 liters of raw liver puree (yummy) daily would allow enough cobalamin, in this case, AdoCbl and MeCbl primarily, to be absorbed BY DIFFUSION through the intestine wall. We do the same thing with concentrates of the cobalamins by using them sublingually. They go directly into the blood by diffusion without being attached to TC2 (HTC2, HOLO-transcobalamin 2). In the 40s liver extract was experimented with for the same purpose as they tried to find out the wonder ingredient in liver, “protein mystery factor” as it was sometimes called. Many people choose to die instead of taking the fear factor cure of 2 liters of pureed liver daily, chugged. Liver extract worked as well. When they tried it on those with PA, they got better. When they tried it on schizophrenics, they were released in 3 days from the mental hospitals. Women hospitalized for post partum depression were cured in 1 day by liver extract.

    Liver extract came on hard and fast and worked rapidly. It is reasonable to think that the extract contained the AdoCbl and MeCbl that were later documented as the two major cobalamin forms in liver extract. Further it is reasonable to assume that it contained l-methylfolate, the animal form of folate, as liver is rich in folate as any nutrients list will show. As most all red meat contains various carnitines, liver extract would almost certainly have contained L-carnitine as well as a rich assortment of amino acids. The rapid and extensive action of liver extract containing “protein mystery factor” is, as far as I can tell, fully duplicated by AdoCbl, MeCbl, L-carnitine fumarate and L-methylfolate, the deadlock quartet. Cyanocobalamin, the Nobel Prize winning lab mistake couldn’t duplicate any of the effectiveness of protein mystery factor in liver extract. All it could be documented to do was to lower MCV sometimes. However, Thorazine and other antipsychotics were just coming on the market so the neuropsych problems were conceded to the pharmaceutical companies and the ONLY thing that mattered was Pernicious Anemia.

    Can you point to any papers, research, whatever, that details the “distribution by diffusion” mechanisms?

    That has been completely ignored for 60 years as far as I can tell, in the effort to push the CyCbl and HyCbl solution. The whole effort has been to prove that once HTC2 is saturated, that is the story regardless of the kind of cobalamin started with. It appears to merely embarrass all that ignored the real effectiveness of protein mystery factor and liver extract. They all pretended that didn’t exist. The x-ray crystallography study in 1959 in the UK that finally identified the mistake was totally ignored in practice. They have been too busy gluing paper wings on CyCbl to make that pig fly to find out one of the reasons for the dramatic effectiveness of protein mystery factor in liver extract.

    My assumption is that in this process no conversion of the methyl or adenosylcobalamin would be necessary

    I would be inclined to think that you are 100% correct. It gets rid of a wealth of assumptions, most of which are “traditional” rather than proven. The direct absorption and diffusion (injections too) of active AdoCbl and MeCbl have almost magical effects. Too much CyCbl by injection can cause blindness as cyanide kills the optic nerve in one form of hereditary optic neuropathy. Large injections of HyCbl don’t generally make a qualitative difference. Lots of studies have been done showing the therapeutic equivalence of injected versus oral inactive cobalamins. 10mcg of active MeCbl absorbed via the active system do only a little more than CyCbl and HyCbl. 100mcg of absorbed AdoCbl and MeCbl are 100 to 10,000 times by my best estimations more effective by any of several measures than any amount of HyCbl or CyCbl taken in any way.

    You are saying that all the lettered diseases are essentially utilizing enzymes that would not be necessary if we had an adequate amount of the naturally occurring cobalamins.

    The studies of such started with infants undergoing “failure to thrive” which is deadly if not corrected. A whole lot of this appeared with a switch to formula. As we may create within our bodies 100 or more temporary and byproduct and end product cobalamins there is an extensive evolved mechanisms for forming exactly the cobalamin needed for each task. We end up with CyCbl after HyCbl, AdoCbl or MeCbl are further oxidized by CN and becoming CyCbl. Nitrous oxide does essentially the same thing. Glutathione does the same thing.

    So a paper such as this, that goes into minute detail about the processing of cobalamin in the cell is essentially referring to the “Work around method.” Do I have your thought right so far?

    No. The processing in the cell, the elaborate absorption and all that are the natural and normal processing. Reading Wheatley’s paper, she stated that it appeared that HyCbl handling inflammation poorly and leaving a lot of loose ends, is the work around. She first wrote 3 papers (Scarlet Pimpernel of inflammation papers, I, II and II) on HyCbl and inflammation exploring it in great detail before writing the Giant Gorilla … Adenosylcobalamin paper. AdoCbl handles inflammation radically better and doesn’t leave all the loose ends leading to other diseases. The big thing is that as far as supplying the body with the needed amounts of AdoCbl and MeCbl, being able to recycle CyCbl and HyCbl, common end product cobalamins back to usability via an expensive process that counts on a person not being truly deficient in AdoCbl and MeCbl.

    In reading the paper it is clear that for AdoCbl to deal with inflammation it must be delivered intact in quantities sufficient for each and every cell needing it at the same time. She was also positing the same “supra biological” quantities of HyCbl for the papers she wrote on HyCbl. What I have done is through titration found the approximate lower limit of AdoCbl dosing to produce “radical” inflammation processing. This lower limit is at the top of the biologically achievable amounts of AdoCbl and MeCbl. A large serving of steamed clams or oysters and drinking the broth can likely do it. A concentrated extracted liver concentrate as a soup or stew can do it. My grandfather was kept alive by having the concentrated extract of 5 pounds of liver daily for 30 years after his ALS diagnosis, surprising all his doctors. The case for diffusion distribution was made in the late 30s and 40s with liver extract following 2 liters of pureed raw liver in people with pernicious anemia who would have otherwise died because they could not absorb b12 via the IF and TC/HTC mechanisms.
    junkcrap50 likes this.
  6. dbkita

    dbkita Senior Member

    For me at least when I had to focus on eating almost exclusively for what had high potassium and still was taking lot of supplements so total intake was like 11 grams a day ... that was insane looking back.

    Now I need only 6.5 grams or so total intake (of which maybe 1200-1500 is supplemental using potassium gluconate powder and a few potassium citrate pills).

    I actually feel much better not pushing things so hard that I needed absurd amounts of potassium (which I was excreting like crazy into the toilet).

    This btw is part of the reason that the "new cell growth - healing" theory for explaining high potassium need is totally flawed. The numbers simply do not add up nor do they explain the exorbitant 24 hour excretion numbers. End of story. However, whenever I bring this up, no one says a peep since quite honestly no one really knows what is going on and the cell growth theory has become a sort of dogma on these forums. Sigh.
    jeffrez likes this.
  7. dannybex

    dannybex Senior Member

    My eyes are too fried to read the long posts in this I don't know if you've mentioned them already, but do you mind listing (or reposting) the supps that helped improve the function of your Krebs Cycle?

    Thanks in advance. :)

  8. dbkita

    dbkita Senior Member

    creatine pyruvate, calcium pyruvate, d-ribose, R-ALA, vitamin B1, b2, b3 (niacinamide), b5, biotin, adb12, magnesium malate

    I also had to work to get my ferritin up to a reasonable level.

    Currently trying to relieve body burden of aluminum and cadmium (wtf is that doing there?) since they also disrupt Krebs cycle function
    dannybex likes this.
  9. Freddd

    Freddd Senior Member

    Salt Lake City

    Hi Jorlev,

    With AdoCbl-MeCbl absorption, are you saying that 100mcg (50mcg AdoCbl / 50mcg MeCbl) would be absorbed from taking 1/4 of 1mg (250mcg) sublingual AdoCbl and 1/4 of 1 mg (250 mcg) of MeCbl? Just trying to clarify.

    When the tablets or capsule contensts are of the rested brands, and I have also tested pure crystal pressed into slivers of apple and bread, with about the same results, the key is a long holding at relatively high concentrations. So the amounts used sublingually or under lip even better for less saliva flow meaning higher concentration, the diffusion through the skin, and held for 45-120 minutes or longer typically can yield an absorbtion of 15-25% (range 10-33%) does occur. These smaller amounts can be compared via effectiveness since they are not at all visible in the urine. I am not oriented aroind an amount specificed does. I prefer "titrate to criteria". The criteria for the AdoCbl and MeCbl is an awareness of startup of all varieties, which then each needs to be dealt with while cobalamin dose is on hold. Once one gets enough to turn on healing all day, twice as much makes no difference. In the N=1000 questionair trial with single dose response tests I performed nobody was able to distinguish a difference between a 1mg sublingual and a 5 mg sublingual. There was no difference in perceiving startup or extent. However the MIX of the two cobalamins increased the percentage responding.

    Regarding conversion, are you suggesting that equal amounts of MeCbl and AdoCbl should be taken on the off chance that ones body does not convert well between the two or do you still favor taking more of MeCbl than AdoCbl.

    At these small quantities ratio appears to make no difference at all as long as there is enough of each. Over time as the two reach equilibrium differently, people need to customize their program. The only differences perceived at all, besides not getting enough to reach equilibrium occured with injected doses of 60mg/day or greater of AdoCbl when taking 30mg injected daily of MeCbl. It appeared to casue MeCbl CNS deficiency symptoms. That may just be competition crowding the MeCbl out for the instant it is needed. Injecting 180mg daily of 3 star MeCbl along with 10mg of 5 star MeCbl casued similar MeCbl deficiency symptoms. Injecting 30mg of the same 3 star MeCbl with 10mg of 5 star succeeeded in causing sufficient 5 start MeCbl to enter the CNS to be effecrtive in CNS healing. So the ratio of effective MeCbl to ineffective MeCbl is important to consider. In that context it may just be that AdoCbl is "ineffective MeCbl" in terms of competition.

    As a person heals many things and adjusts doses and adds items to maximize continued effectiveness the ratio will be whatever it is. Some people need daily CNS penetrating doses of AdoCbl. Some people need daily doses of AdoCbl and some people appear to need once a week to once a month doses of AdoCbl. As for me and others who have reported on it, I find that If I take 2.5-5mg of AdoCbl sublingually when I take 10mg of SC injected MeCbl I get adequate CNS penetration by the AdoCbl. They appear to have a joint diffusion gradiant that gets both of them distributed.

    Regarding the Wheatly study, I'm not sure if I got the right take away from it. Was it implying that Adeno helps lessen ONOO while preserving the NO needed for vasodilatation? I've read conflicting things on NO. That it's needed for vasodilatation and that lack of it restrict blood flood and therefore nutrients needed for nerve function / repair. If MeCbl is a NO scavenger aren't you concern that megadoses are depleting too much NO even if AdoCbl is preserving it. How would one know if they have too much or too little NO? Your thoughts appreciated

    Let’s consider some side issues in this. In here paper she cites a paper noting increased penile erectile function in mice with AdoCbl. This is well noted in humans taking AdoCbl (and other needed nutrients) as well. Lack of penile erectile functioning is a common b12 deficiency symptom. Being able to stop needing Viagra or Cialis for erectile functioning would appear to be an indicator that things are working properly. Routine healing of peripheral neuropathies would indicate that the nerves are getting sufficient blood supply. There is a gadget that is a customized TENS unit called the ReBuilder that through electronic stimulation helps restore and rebuild the nerves. It works pretty well in my experience. Also, consider the pharmacodynamics of the various cobalamins. Considered NORMAL is a 20-50 minute serum half life following absorption. All in all 99% is excreted via the kidneys in 24 hours based on an ordinary folic acid fed population. A single suitable sized does of glutathione will cause the dumping from the body of apparently essentially all unbound cobalamins in 3 or 4 hours. At a time when I was taking 10mg 3x per day by injection, the normal 4 hour visible cobalamin in urine was about 5mg with folic acid, 2mg with l-methylfolate and 60mg with glutathione. Six weeks of glutathione can require the startup of Viagra for erectile functioning. Of course it is also damaging the nerve signals from the penis so who knows the actual cause of loss of function. As research indicates 99% of unbound cobalamins are typically excreted UNCHANGED in 24 hours, whatever the MeCbl is doing, it isn’t becoming nitrocobalamin or any variation of that. So it isn’t functioning as a NO mop. In fact that was a criticism of MeCbl by those saying how superior HyCbl was at doing just that, based on Wheatley’s earlier 3 papers. So, small dose, large dose “megadose”, makes no difference in the NO. As I have titrated for effectiveness, if I were doing something that had an adverse effect, it would likely have shown up. Or at least it would have shown up during the several month series of 180mg/day injected MeCbl. Instead, I did have a lessening of CNS effectiveness very similar to what happened when the Jarrow MeCbl became inadequately effective, only the Jarrow didn’t work as well as the 180mg of 3 star MeCbl injected. Much less of it made for much worse effectiveness. The key to all of this is recognizing relative effectiveness and learning as rapidly as possible from each change. Most the really effective trials are obvious within 24 hours and confirmed in some while. For instance, I feel the difference in CNS effectiveness in <24 hours but can’t tell direction for up to 2 weeks if it isn’t clear. Change itself in the CNS is apparent but not necessarily the direction.

    My CRP dropped to < 1.0 in the month following AdoCbl startup. I hope this gives you the info you find helpful. If most everything heals and nothing new goes wrong I use that as evidence that things are working. Most of the new things that go wrong are of the induced deficiency nature. A person not taking all the usual vitamins, minerals, fats, other nutrients will spend years chasing down each new “most limiting factor” as one thing after another stops healing as an induced deficiency. It is an extremely difficult and tedious puzzle to do it that way with only small and slow success.

    As I was already taking the fish oil (Salmon oil first, then omega3), lecithin, fish oil A&D, 5000 iu of fish oil D, all the usual vitamins and minerals and a lot more for decades I can’t tell the effects of adding these later. I didn’t have to chase down any induced deficiencies beyond increasing zinc and potassium, and adding TMG, LCF, l-methylfolate and AdoCbl/MeCbl, SAM- e.

    What ratio and amounts do you take? I know you take 25K MeCbl. Would you take 25K AdoCbl too??

    I currently am taking 10mg Enzy and 3.3mg Anabol in one dose maximized with 3 hours holding yielding an estimated 4mg absorbed. A second dose of 10mg of Enzy, absorbing perhaps 3+mg. Then a third dose of 5mg of ENZY and 40mg (currently experimenting so this amount is changing for trial) of Kirkland 5mg MeCbl to give me a CNS penetrating dose allowing me to maintain CNS function and current degree of damage and more or less tread water. Because of the rapid rate of dissolution the rate of absorption isn’t as high I would like. So lets say I’m getting about 9mg of b12 out of the 45mg I take. So I am getting about 16-18mg more or less of absorbed b12 more or less, total which includes perhaps 1mg of AdoCbl and once a day CNS penetration. I have experimented with as high as 50mg nominal dose, say 10mg absorbed, a day of AdoCbl and as long as I maintain equilibrium, and don’t take glutathione or NAC that clears it all, I have no startup and no difference in effects. Taking that dose every day though DOES make a small noticeable change in inflammation in the only inflammation I am aware of. More makes no additional difference that I can tell.

    I currently am taking 10mg Enzy and 3.3mg Anabol in one dose maximized with 3 hours holding yielding an estimated 4mg absorbed. A second dose of 10mg of Enzy, absorbing perhaps 3+mg. Then a third dose of 5mg of ENZY and 40mg (currently experimenting so this amount is changing for trial) of Kirkland 5mg MeCbl to give me a CNS penetrating dose allowing me to maintain CNS function and current degree of damage and more or less tread water. Because of the rapid rate of dissolution the rate of absorption isn’t as high I would like. So lets say I’m getting about 9mg of b12 out of the 45mg I take. So I am getting about 16-18mg more or less of absorbed b12 more or less, total which includes perhaps 1mg of AdoCbl and once a day CNS penetration. I have experimented with as high as 50mg nominal dose, say 10mg absorbed, a day of AdoCbl and as long as I maintain equilibrium, and don’t take glutathione or NAC that clears it all, I have no startup and no difference in effects. Taking that dose every day though DOES make a small noticeable change in inflammation in the only inflammation I am aware of. More makes no additional difference that I can tell.
  10. Freddd

    Freddd Senior Member

    Salt Lake City

    Hi Dbkita,

    I have a couple of questions along the way here before I dig into this one.

    Do you take Metformin? Do you have insulin disorders of any kind? What about adrenal gland malfunction? Also, your age could help in understanding things. Any chemotherapy type drugs for any reason; even as topical application?

    Do you have Parkinson’s or any reason to think you are heading that way? Do you have chronic anxiety and/or panic attacks? OCD? Abnormal benzo effects sometimes called “tolerance withdrawal” specifically with Klonopin or Valium? Do you have any reason to suspect limbic circuit mood and personality responses are prominent? If you have ANY positive response to this 2nd portion of questions carnitine may hit like 100 tons of bricks. A person trying carnitine who has this situation, might want to start at 100mcg divided in 3 doses a day, and titrate most carefully.

    What I get out of your paragraph is that the Deadlock quartet had you deadlocked on AdoCbl/l-carnitine. You clearly haven’t reached equilibrium or a dose of AdoCbl would have zero noticeable effects. I would suspect that l-carnitine may explain a lot and start with a kick you might not believe. This is where ATP startup, Krebs cycle, becomes a major situation. On the other hand it may make a huge difference but not a hyper effect.
  11. Idie


  12. dbkita

    dbkita Senior Member

    No Metformin or any chemotherapy drugs.

    No insulin disorder I am aware of. Fasting glucose has stabilized in last year at 89-93 (used to be in low 70, high 60s for years which sucked). But .. my LDH is VERY low. So not sure if that is relevant.

    I have a very rare autoimmune disease that target GAD antibodies in the CNS and is known as Stiff Person Syndrome. I also have Celiac's. My doctors believed there was a chance that my Stiff Person Syndrome was being aggravated by ingesting gluten and the ongoing Celiac's. And fortunately I am one of the lucky ones where getting off all gluten seemed to slow progression. However not before massive damage was done to my body as my adrenal output went to nil (not just irregular cortisol but all other adrenal hormones), my reverse T3 was around 800, and I had lost 80 pounds. Norepinephrine and glutamate were out of control for many years and my sympathetic nervous system was on fire. I have no frame of reference to describe how bad 2008-2009 were. A neuroendocrinologist saved my life at the end of 2009 by intervening with hormonal support that at least put somewhat of a brake on the inferno of pain (note painkillers did zilch for me, not fun). But the SPS was not diagnosed until summer 2011, along with the Celiac's.

    Currently I take supraphysiological doses of glucocorticoids, take Cytomel, DHEA, and some minor dose of Klonopin (0.4-0.5 mg)and baclofen (20-30 mg) to help with issues sleeping. By getting off the gluten and the glucocortiocoids I have managed to chop the GAD antibodies back in half (though measurement in the periphery is no guarantee of drop in the CNS, but clinical symptoms are MUCH better).

    I have also been on some form of methylation for 2+ years now and some form of Krebs cycle support for about a year. Other big things that helped was going on Florinef last year (massive improvement) and more recently increasing Cytomel dose and adding adb12. Like I said since around the adb12 was added and some other changes, suddenly supplements that used to bother me like biotin, alpha lipoic acid, b1, and b5 now work well for me. Calcium also. Vitamin D is still a new frontier (I take 2500 IU per day, but my levels of the inactive form are low especially relative to the active form).

    At this point my doctors and I believe I am winning the war on my autoimmune disease, but I am focusing on now fixing the collateral damage. The immune system seems to be in better balance and I have managed to reduce my glucocorticoids by about 25% with no apparent negative effects in the last couple of months.

    One continuing concern is my inability to gain weight. I eat 4000 calories a day and my weight is at best 155 lbs on a 6'2" frame. I used to be about 190 lbs when I was healthy. When I lost my weight in 2008-2009 I was 120lbs for comparison. I eat 200+ grams of protein a day, 130+ grams of fat, and while not Atkins I get like 60-70 grams of carbs (just don't do well on starches).

    No Parkinson's though low dopamine and serotonin are issues for me. For two years dopamine was so low, I was so restless could not sit, and had minor tremors. Going on bromcriptine helped but when real diagnosis came in, weaned off bromcriptine and focused on treating SPS. One theory with the dopamine and serotonin is due to low BH4 (before it was presumed to be low iron but that has been resolved, finally) based on neopterin / biopterin labs.

    No chronic anxiety or panic attacks (though I was on the edge of that all the time in 2009 but even the docs said that was due to the pain (*shudder*)). I don't seem to have much issue with Klonopin, take only at bed time, small dose, started last Spring, titrated down to 0.4-0.5 mg from 1 mg. But not sure how easy it would be to get off, I don't make my own GABA very well.

    What do you mean by "suspect limbic circuit mood and personality responses are prominent"? Don't think I can answer that one yet. I will say in the past when I tried like 250 mg of carnitine I had really bad insomnia and some anxiety. But I have not tried it in 2 years. Everything I tried sucked badly 2 years ago and was unimaginably bad 4-5 years ago.

    What would you suggest then for titrating the L-carnitine? Putting it in liquid and letting it dissolve and use an eye dropper? I suspect carnitine is important. The R-ALA 300 mg that I started taking last month was a big win. I also wonder if CoQ10 would be helpful. Used to take that also but caused me reflux all the time.

    I have managed to string together about six continuous victories (increased T3, zinc carnosine, R-ALA, doubling vitamin E, increasing B1 + B5, biotin 200 mcg) in the last two months with supplements so I am probably due for a disaster lol :)

    Before that adding in Adb12 (now 2.5 grams per day Source Natural) and switching from Jarrows B12 to Enzymatic Therapy B12 tabs were also beneficial (sigh they really messed up the Jarrows didn't they). But I also have to confess getting rid of TMG and SAMe was really important (those two were driving me to high NE states and OCD last spring, hence the klonopin I am stuck with at the moment). Those were the "peak" times when the potassium requirement flipped out of control (rode that wave for many months ... uggh), i.e. hypokalemia on 11 grams intake a day (gah!).

    To review: currently I take 800 mcg methylfolate in one morning dose as FolaPro. I take 25 mg P5p as sublingual (source naturals). I take 2500 mcg methylb12 as Enzymatic Therapy and 2500 mcg Adb12 as Source Naturals. I take plenty of calcium and magnesium and intake of potassium is now 6-7 grams in food and supplements. One key thing is 1500 -2000 mg of sea salt a day. No TMG. Zero folic or folinic acid. No SAMe. Some vegetables but not nearly as much at the meat, nuts, etc. No starches. Low glycemic index.

    Other supplements that may be of less interest: I take 2-3 grams of Na ascorbate per day. 2500 IU vitamin D. Not vitamin A (don't do well on that similar to D). One Iodoral to keep serum iodine up. 800 IU vitamin E. 15 grams D-ribose. 3 grams creatine pyruvate. 200 mcg selenium. 300-450 mcg molybdenum. 32 mg of zinc as zinc carnosine. 2000 mcg biotin, 100 mg b1, 100 mg B5, 100 mg B2, 500 mg B3, 300 mg R-ALA, some borage oil, no fish oil (messes me up inside). No copper (I get enough in nuts).

    If you want I can send you a list of meds and supplements via a private communication. My intent is not to clutter this thread.

    Anyways looking forward to your thoughts.

    And thanks btw for the 1:1 ratio of meb12 and Adb12 and also the one hour time lag of b12 sublinguals to methylfolate. That has seemed to help also. Do note I only take one dose right now in the morning.
    junkcrap50 likes this.
  13. Freddd

    Freddd Senior Member

    Salt Lake City

    Hi Dbkita,

    This btw is part of the reason that the "new cell growth - healing" theory for explaining high potassium need is totally flawed. The numbers simply do not add up nor do they explain the exorbitant 24 hour excretion numbers.

    Let’s examine that. First of all that cell formation hypothesis comes straight out of 60 years of b12 research, such as it is. I have no reason to distrust this part of the studies as it is quite consistent across many kinds of studies. Now it is possible that it is a totally unfounded assumption that has been universally adopted, but there is also nothing to suggest that. In most people it appears to function that way. I have been carefully monitored by my internist for the past 10 years during this entire process. I do not have any abnormal potassium excretion. In fact Lasix, not a potassium sparing diuretic, doesn’t appear to increase my potassium loss. High potassium loss in urine occurs when way more potassium is consumed than is needed. It is part of the homeostasis mechanism. The question is, why do you have what you interpret as Hypokalemia while at the same time dumping large amounts of potassium? I eat 1200-1500 calories a day, total. While potassium is very common throughout our diets, that doesn’t maintain my potassium above 3.6 or so. I have had low potassium spasms since childhood. I always wondered why higher altitude made them so much worse. I only found that answer in the past 8 years. I can repeat that every year if I am only at high altitude seasonally. So it clearly ties to cell formation for me.

    I had to increment my potassium at each of the layers of healing that I have described except CNS. My need for potassium almost stops when paradoxical folate deficiency starts screwing my cell formation and I start to add water at 3 pounds a day. Then when I reverse it and the water pours off at almost the same rate I need more than usual potassium for a few days and then it levels off at lower rates. The rate itself has slowly declined from 3000mg additional I needed a year ago and a few years before, to about 2000mg now and my muscle formation has slowed down as it has become normal. Many of my tissues have been healing and maybe rebuilding for 10 years now. My skin is the best it has ever been and a lot of shallow scar tissue has sloughed off including most of the acne scars on my face.

    It would appear that many if not most of the people have experiences more like mine than like yours. So maybe the question to consider is why are you different? About 20 years ago an honest doctor told me to move on. I say “honest” because instead of playing “blame the patient” and calling me all sorts of names and kicking me out of the practice because my situation didn’t confirm to his understandings of how things were (the usual kicked out experience) he told me “I don’t have any idea what is wrong with your body but clearly something is very wrong and clearly getting worse. My other patients get well or have something clearly at cause. What makes you different in that you never get well? Nothing works and there is no clear reason.” And then he asked the critical question. “What makes you different from all the rest of my patients?” It’s basically the same question I used to find provider fraud in health plans and at a larger scale, insurer misbehavior. We worked for the plan trustees, not the insurance companies.

    So why were you excreting so much potassium while having Hypokalemia symptoms telling you to take more? What makes you different from those of us who reach an equilibrium between 1200 and 3000mg of additional potassium? What else distinguishes you?

    Perhaps too much calcium or other imbalance in minerals can give that effect. We are looking at balance in minerals. I’m just asking questions. I don’t know the answers. Somebody else might notice a match to their patterns that they figured out. In any case starting l-carnitine might tell us a lot. Good luck.
    junkcrap50 likes this.
  14. Freddd

    Freddd Senior Member

    Salt Lake City
    Hi Idie,

    So, you no longer use injections? Is that because they are only 3 star?
    Yes. Three injections a day is a pain in so many ways. If it doesn't give me a clearly superior result there is no point. With the Jarrow and Enzy to a total of 36mg and than 3x10mg of the injections, I was holding my own in the CNS. The when the Jarrow changed I got worse but ony in the MeCbl-CNS compartment. The relapse and progeression made clear that the FMS pain is identical to the pain casued by a certain stage of SACD, with a pure MeCbl-CNS deficiency. My body was fine, my exercise and stamina was great but sleep disorders were back. I had narcoplepsy start again. Then I had some dehydration and over heating on a very hot day and suddenly I lost my balance and it stayed gone for a week. Demyelination would be the guess considering SACD is well established and it can respond to challanges similarly to MS. I bought about 60 bottles of ENZY and discontinued everything else. I had done the discontiunance and then a day later tested with a 30mg dose of ENZY. All the worst was over in 2 days then except the sleep disorders. That took another couple of weeks and a lot Metafolin for a couple of weeks which I had waiting for me at home as this happened on the road. I'm in the subgrouping for which "L-methyfolate has an astonishing neurological effect". It is very much a cofactor for SACD, at least in this subgrouping". The phrase comes out of some of the Deplin or other brand of high dose Metafolin research.

    I can't give the Kirkland a full 5 star effectiveness. but it's effects are complimentary enough with the Enzy that it gives me a decent boost into the CSF, but it isn't good enough to dilute with the 3 star injectable. I've never run into one quite like this one before. It is keeping me in a similar equilibrium zone as far as the best I've done since the glutathione trial trashed my nervous system.

    If I get 5 star I will repeat the 180mg/day injections series to see if quantity does matter beyond the threshold.I wpuld love to push the damage back to where I get enough muscular feeling back again to regrow the muscles. I know from experience that it will hurt like hell for a couple of years at least. I would also probably be able to put an end to the pain along my entire C3 dermatome. So here is hoping to find the good stuff and establish a better equilibrium.
  15. dbkita

    dbkita Senior Member

    Alright fair enough. That is a distinct possibility.

    First the hypokalemia showed up as four CMP labs of serum potassium in the range of 3.1-3.3 over a span of six months. Not severe, but considering how much potassium I was taking .... well you get the idea :) The excretion test was done in the 4th month and was 250 mEQ lost per day with an intake of at that time 10-11 grams for some time. These were fasting values in the morning. Later once I had scaled back on a couple of things as I already discussed, the serum bumped to 3.7 (at an intake of still 10-11 grams) but was observed to reach 4.5 six hours later after the first fasting morning test. Corresponding intracellular RBC potassium reading were 87 in the morning and 82 in the late afternoon on the same day, drawn at same time as the serum samples.

    Note muscle cramps would get progressively worse through the later night and into the morning especially in lower legs and calves and feet and ankles which is consistent with lower potassium. But improve as day went on, etc. I also had other pain symptoms that would be heightened in the back, neck, headaches, shoulders, etc.

    Now I take only 6.5-7 grams per day (both food and supplements) and my fasting serum is 3.5 but I have no muscular cramps (only minor lower limb achiness late at night, minor spine tightness but those can easily be my autoimmune disease). I have yet to get a new timed test over the day but I am sure my better symptoms suggest I am in bounds more often. I suspect though the intracellular concentrations still suck. Hmmm maybe a new excretion test is in order also. Note so far all kidney and liver tests have been fine.

    The other nugget, is a recent hair analysis done by ARL that without telling them anything in terms of symptoms they reported a extremely low Na / K interstitial value. Note I take 1700-2000 mg of sea salt a day, otherwise I have dysautonomia type symptoms. Supposedly the abnormally low ratio suggests catabolism and I cannot gain weight on 3500-4000 calories a day.

    One thing that may distinguish me is high levels of glucocorticoids.

    Now that I think of it during the potassium wasting period I was also not only on stronger methylation support but I was told to increase my prednisone to 15 mg from 10 mg (on top of 4 mg of medrol I always take) to try to manage some of my nastier symptoms. WIth the other aforementioned improvements of recent I have scaled back to 10 mg prednisone + 4 mg medrol (there is also 0.1 mg florinef constant throughout the whole time). Supposedly the low Na / K ratio suggests glucocorticoid excess relative to mineralcorticoid behavior.

    Perhaps I am trapped between higher need for potassium via methylation but at the same time something going on with either my Na-K+ ATPase pumps or 11 beta HSD1 or too much glucocorticoids that is driving me to high excretion.

    Thank you for the info. It is good to get a new perspective from time to time.

    I was not aware that others did not have heightened excretion. At least one other poster had complained about this on the forums. Doesn't matter maybe. I still question though on theoretical grounds why others have to double their total intake (some report 5 grams needed to supplement on top of diet) and yet it is all going to new cell growth for months even years. There would have to be some equilibrium apoptotic turnover otherwise the total body potassium store would be too high. People may heal but total body weight does not lie provided it is all not edema. However, I do agree then that something else must be going on for me if the excretion is an abnormal clinical finding for people on methylation protocols.
  16. adreno

    adreno PR activist

    I have a problem with the "new cell growth" theory of hypokalemia. It makes no logical sense. If this was truly the case, then we would see other people developing hypokalemia from donating blood, after having accidents, surgery or chemotherapy, and in athletes. Also, the hypokalemia isn't a startup effect. For me I lasted the entire 6 months I was on high dose methyl donors. At one point I needed 10 grams of supplemental potassium daily. That cannot be a healthy condition any way you look at it. I had severy arythmias and tachycardia on the protocol. Just felt majorly unstable.

    I do not believe that more is always better when it comes to methylation and healing. I have already posted threads with studies showing problems with excess methylation, and studies showing methylation and healing effects maxing out at certain doses.
    junkcrap50, jeffrez and Lotus97 like this.
  17. Red04

    Red04 Senior Member

    The only potassium my wife had needed during the past year was during pregnancy. She no longer takes ANY potassium outside of her diet. Her diet is probably in the 1000-1500 calorie range on average.

    Early on in the protocol she needeed 900-1200mg daily to subside leg cramps and headaches.

    I don't know when the need completely went away as she took 2-300mgs as a safeguard up until a year ago. Sometime within one year of starting the protocol probably.
  18. UM MAN

    UM MAN Senior Member

    dbkita, how would excess ZONULIN fit into your medical model?
    Leaky gut and blood brain barrier.
  19. Lou

    Lou Senior Member

    southeast US
  20. Freddd

    Freddd Senior Member

    Salt Lake City
    Hi Dbkita,

    Things here and there to start. These are not answers, just possible links or considerations and places to look.
    One more question: What does nitrous oxide do to you?
    In asking the question in this way, “What is different that COULD affect potassium?” A quick and shallow reading points at some possibilities for investigation.
    Adrenal problems can cause increased potassium loss, even stimulating potassium excretion to dangerously low levels. Affects on electrolytes in general can really get things messed up (highly technical like “Doctor, I dropped a f****** anvil on my foot”, Buddy Hacket). A GABA problem can affect the ion channel in cell membranes causing more or LESS uptake of potassium, causing low potassium effects regardless of quantity available.
    The very low LDH may perhaps be because of the GAD antibodies. That would make sense.
    MeCbl can control neurological glutamate toxicity. MeCbl is generally neurologically protective.
    These are very general statements and it is a complicated system.

    Micro-titration of L-carnitine

    While LCF (sometimes ALCAR) works in a predictable way with the other cofactors, it is at least bi-modal. One of the predicable ways it works is in a hyper sensitive response. That is terrible if not expected and it can be managed. This response has been called all sorts of things and lots of names applied. It isn’t “detox”. It isn’t “excitotoxicity”. It is a hypersensitive ATP startup, as the mitochondria come up to speed, in at least one very specific portion of the brain, limbic circuit, which can set off extreme responses to what appears to be dopamine changes in starting up the mitochondria. Recent studies suggest that some decades of these deficiencies, AdoCbl indicated by elevated CSF MMA and decreased CSF cobalamin (the contribution of carnitine is sort of recognized because the attempt to fix it with 3 gram infusions is done) causing malfunction of the mitochondria in parts of the brain, limbic system specifically, can cause Parkinson’s. People who look like they are headed this way appear to often have “Parkinson’s personality” characteristics often from childhood. Whether this indicates anything to do with hyper response to AdoCbl/LCF and dopamine affects from nutritional items and benzos I don’t know. There is a great deal of missing information so it is not terribly clear. There are more questions than answers. This whole branching of CNS-AdoCbl is pretty much unknown because it has never been studied because of the focus on CyCbl, HyCbl and folic acid. This is part of the corruption of the system is caused by 60 years of studies of the inactive and inadequate forms of the vitamins. The main branches by CSF cobalamin studies with low cobalamin and elevated MMA appear to be ALS (other unknown factors too) and Parkinson’s and who knows how many unknown unrecognized variations based on all the many possible permutations and comorbidities.

    How all these things tie in with adrenal problems, potassium, and so on is not known

    While most people can take relatively normal levels of carnitine, sizes available typically range from 125 to 1000mg. In treating Parkinson’s sometimes 3 grams (3,000mg) are given IV.

    One of the mysteries of this whole business is why some people, like perhaps most here, have depressed CSF/CNS levels of cobalamin unaffected by the body level.

    Another mystery is how effects can be very local, much more so than by levels of healing or compartments.

    I am trying to share experiences and observations so that people who are so inclined to experiment. This does not constitute advice to do so. There is very little information on this and I am trying to provide an arrangement of the information for understanding. For me to regress the SACD damage in my brain and cord required getting mitochondria and methylation working. I did not have the limbic responses being described though LCF made as much difference to me as everything else combined and was the needed factor with all others in place to cause the edema to subside and muscles to rebuild. My thigh muscle started out the thickness of my thumb on top of the thigh. It further had a large effect on my mood reducing depression, increasing aerobic capacity rapidly and extensively.

    So, the question is, can this kind of damage be controlled, preventing further damage, can it be regressed to a less damaged state and made more functional or what? I don’t know. In my opinion healing won’t happen if function isn’t restored to the mitochondria. Hundreds of reactions are dependent upon adequate ATP. Such a tiny dose of LCF making such a hyper response has to indicate something. With the MeCbl, AdoCbl and l-methylfolate generally the more and more severe symptoms a person has the stronger the response, if other deadlocking items are present. The more symptoms a person has the broader the response.

    So there is a subgroup here, and anybody could be a member of multiple subgroups, that exhibits mild response to AdoCbl and gangbusters response to L-carnitine fumarate (sometimes ALCAR) or the liquid freebase l-carnitine. Brands made from Sigma Tau carnitine appear to be more consistently effective. When a person has had, by response and symptoms, AdoCbl/LCF deficiency in the brain, and specifically the limbic system, certain neuropsyc symptoms are often present, though it appears to span a range from none to very extreme response, possibly depending upon duration and damage. AdoCbl is not a controllable “accelerator”. You get it into the mitochondria and it stays. It takes months of no AdoCbl to make even a tiny difference. On the other hand LCF can be given in anywhere from tiny to large amounts and in smaller amounts is largely effective for about 36 hours or so before half life does away with it. The limbic neuronal mitochondria have an effect on dopamine. Anxiety, fear, anger and many other mood and personality factors can be affected. Too much LCF can cause an out of control intolerable level of response. To quote one person who had this sequence from “too much” LCF in this case it was about 1mg orally. Over a period of 36 hours the person experienced growing anxiety, fear, panic, rage, homicidal rage, profound depression. And it was completely out of conscious control. It could be made worse by getting wrapped up in it but it just had to be waited out. And it is repeatable by the person. There are of course variations but the pattern itself seems to be similar for the person each time. Holding at a constant level of LCF by dividing the daily dose in 3 prevented the cycling through the moods as LCF level increased and decreased. A total dose of 100mcg had no effect beyond a slight “energized” feeling but coming out of that could produce the tail end of the cycling, the depression. 3x33mcg daily held it level. It takes about a week at that to reach equilibrium. If it becomes too much decrease slowly to prevent “crash”.

    A precise microtitration can be done with the Jarrow liquid freebase l-carnitine. It has 3.3mg per drop. One drop diluted with 32 drops of water yields 100mcg per drop. Diluted with 98 drops each drop then has 33.3mcg. Store in refrigerator, covered. Discard each day and start with a fresh mix each day. That is based on all sorts of unpleasant experiences from unintended decrease of dose by deterioration. Consistency can’t be easily achieved by mixing dry granules as they are of wildly varying size.

    In a person without hypersensitivity, like me, titration needs to be done. One goes to the beginning of “energizing”. Then if maintained there it does become “normal” after some number of days or weeks. When it has decreased to “normal”, increment again in a proportionate way. I started at 500mg and it was way too much. I dropped to 62.5mg and it was energized but not excessively. Over 6 months I increased to 500mg. TMG decreased the energized feeling. After equilibrium and “normal” feeling was achieved more LCF made no additional difference. Others have also experienced this effect of a modest dose of TMG (500mg or so).

    I was tried on any number of antidepressants through the years. None worked. However, Provigil which enhances dopamine in the brain and is given for narcolepsy was totally blow my mind powerful at the starting dose. I found that ¼ of a tablet was fully effective for my narcolepsy and it was an amazing antidepressant. It didn’t compare in the end to MeCbl, AdoCbl, l-methylfolate, LCF, zinc, TMG, SAM-e and even D-ribose. I was able to taper Provigil after 9 months on MeCbl as it no longer was needed or had much effect.

    It’s clear that this deficiency in the brain affects dopamine. One of the effects exhibited is with benzos. The so-called “tolerance-withdrawal”. At doses of Valium of 5mg and above, Klonopin equivalent dose as well, when full tolerance is reached at the dose, the beneficial effects start becoming overridden by a little known side effect of benzos. They can decrease the sensitivity of the dopamine receptors in the brain producing neuropsyc responses. People think of it as withdrawal but it isn’t. It is a side effect. So more benzo is taken to maintain effectiveness and it too fades pretty quickly into “tolerance” again and side effects are worse, the higher the dose goes, and come to predominate. I developed a program starting about 23 years ago for tapering medications, which I have had a great deal of experience with and the doctor provided tapers never worked. I worked it out with a man who taught CME classes on how to get people off of accommodating drugs. It is highly engineered to get rid of many of the causes of not succeeding and works quite well generally. It is usable even by people having “tolerance withdrawal” and can be calculated for any specified rate of tapering. It can also be used “backwards” to do a very precise “percentage” based titration say at 1% per day. It can be very tedious to do because timing is very precise.


See more popular forum discussions.

Share This Page