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Blood Brain Barrier

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Idie, Feb 2, 2012.

  1. Idie

    Idie

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    Fredd,

    Could you provide a perspective on how or if B12 gets through the blood brain barrier. I believe you have said that many people with MS, Alzheimers, etc have low cobalamin levels in their brains. Aren't B12 molecules too large to get through the blood brain barrier?
     
    L'engle likes this.
  2. Freddd

    Freddd Senior Member

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    Hi Idie,

    So far I have no idea how b12 actually is supposed to get into the CSF. It is assumed that there is an active system. Not too many years ago everybody assumed that b12 had too large a molecule to get through the skin. Now there are patches, nasal gels, sublingual tablets etc that all clearly can demonstrate at least a degree of diffusion through the skin. In the mouth there is a clear concentration-time factor to that diffusion.

    In the literature all the research is based on only an assumption of ONLY distribution by the active distribution system. Nobody talks about the b12 diffusion to the tissues that benefits all of us taking more than a few micrograms a day.

    The Japanese 50mg dose research is all based on an assumption of high gradiant diffusion push into the CSF. They demonstrated that direct 2.5mg injection into the CSF has a similar effect to 50mg/day except that it lasts for 3 months to 4 years with a single such injection instead of daily doses lasting one day.

    So taking advantage of that as demonstrated by the Japanese studies, I and others have found that 4x7.5mg and 3x10mg and 2.15mg are all about as effective for at least some people. Further I have done a trials up to 180mg/day (3x 60mg), and at leat with the quality of mb12 I have (3 star) it makes no real difference over 3x10mg.

    I have to assume that the threshold for diffusion through the BBB requires a serum level of cobalamin at the approximate estimated level of 200,000pg/ml, or 200ng/ml, which if maintained 24/7 approximate the effects of a direct mb12 injection into the CSF, which is a much more invasive procedure.

    I hope that I have answered your question to your satisfaction. It's just that there is no good answer at the moment.
     
    L'engle likes this.
  3. Idie

    Idie

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    Dear Fredd,

    Yes, this is really helpful...thank you. Also, I think I remember you saying that when brains of people with MS, Alzheimers, etc were examined many of them had low levels of cobalamin. Is that right? I ask because I often wonder about the levels of cobalamin in my brain. Thanks for indulging me.
     
  4. Freddd

    Freddd Senior Member

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    Hi Idie,

    They did CSF draws and analyzed the fluid for (in various studies) cobalamin level, HCY and MMA. They didn't use the brains like Igor, and didn't use the brain marked "do not use" which was from Abby somebody.
     
  5. Idie

    Idie

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    Dear Fredd,

    Ha! Your sense of humor is much appreciated. My question was worded rather poorly. I laughed when I read it again.
     
  6. Pea

    Pea Senior Member

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    Fredd, will a neurologist draw CSF to test for B12 deficiencies there?
     
  7. Freddd

    Freddd Senior Member

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    I don't know. The other problem is that there is no accepted standards of interpretation, just a few studies worth of results. The other problem is that even if they had standards there is no saying that they would work or be predictive. The body tests are not. Only a trial is considered definitive. Maybe in 50 years there will be answers from that direction. There are not at this time. For a fraction of the cost you can determine that pragmatically. Responding to a one dose trial of suitable size after pre-loading the body is predictive of further response.
     
  8. Rockt

    Rockt Senior Member

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    So what is the way to penetrate the brain re B12? From my decent and relatively fast results physically, I'm sold on the value of the active b12, etc. protocol. But I can't get ANY improvement in terms of cognitive impairment/brain fog. Are injections the answer?
     
  9. Freddd

    Freddd Senior Member

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    Hi Rockt,

    It depends. After body saturation is reached and all cofactors and critical cofactors in place that are needed by trial, then the 50mg test doses can be tried sublingually, on different days. That can deterimine if larger penetrating doses are needed. For me the answer is yes. A single sublingual 60mg dose of adb12 weekly takes care of that for me. But I need the mb12 injections 3x daily. Depending upon what your first and subsequate trials show will determine whether injection is needed or maybe a single CNS penetrating dose a week is suffiient for mb12. It might also be a missing cofactor at this time. I'll go over your whole program with you and help you set up a some trials to answer those questions if you like.
     
  10. Rockt

    Rockt Senior Member

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    Thanks Freddd. I've PM'd you.
     
  11. rydra_wong

    rydra_wong Guest

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    Too bad they didn't look at Abby Somebody's brain. It would have helped me a LOT.

    Abby
     
  12. topaz

    topaz Senior Member

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    Ive been wondering about BBB dysfunction recently too. What needs to bind with B12 to ensure entry into cells (esp BBB) or what happens if the binding cannot take place? ie normal serum B12 but possibly CSF B12 deficiency.

    I have severe brain fog and this is now by far my worst symptom as it cuts to the core of being human - the ability to think. Its like being in a waking coma at times.

    I too have considered having my CSF tested but I do not trust that appropriate testing would be carried out here (Australia) and even if it was, I would most likely have to interpret the results myself. I havent dismissed this entirely but maybe Ill start with an MRI.

    I came across this article recently about neuropharma and crossing the BBB http://drugdiscoverytoday.com/echoice/may2007/pardridge.pdf
     
  13. brenda

    brenda Senior Member

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    Hi topaz

    I have been using Samento which apparently crosses the BBB and have found indeed that it helps with brain fog.
     
  14. Rockt

    Rockt Senior Member

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    Hi Brenda.

    How much has Samento helped you? Has it been significant? I ask because brain fog/fuzzy head is my worst symptom also and though some things have helped a bit, (ie. d-ribose), it's not significant and lasting.
     
  15. brenda

    brenda Senior Member

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    Yes I would say that while I am on it it helps a lot but I keep stopping it as I have Lyme and the bacteria builds resistance.
     
  16. rydra_wong

    rydra_wong Guest

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    Have you checked your thyroid? If TSH >=2.0, you are hypothyroid, which can cause brain fog. (The lab range includes many sick people. Many studies show lots of health issues (heart and raised cholesterol for instance) are caused by TSH >=2.0 (despite that being in the 'normal' range'). Also fog may be caused by hyper thyroid (but I dont know the range for that).

    I keep going hypothyroid and am making it a mission to keep my TSH at 1.9. I started taking tyrosine - I think everything else comes in my multi.

    TSH is not the end of the story because T3 is the active thyroid hormone. You need to look at that too to see if the brain fog might be due to thyroid issues. Lots of people at the other board found their brain fog cleared up when they cleared up their thyroid issues.

    Rydra
     
  17. topaz

    topaz Senior Member

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    Thanks Rydra

    Yes, I had thyroid actively tested last year. TSH, T3 and T4. All normal. I will double check my TSH result tomorrow.

    The only thing thyroid related that came up abnormal was my iodine (via urine test) which was significantly below the reference range. I am on a thyroid supplement - an Australian practitioner brand containing per tablet;

    Iodine (potassium iodide) 145mcg
    Selenium 50 mcg
    Zinc 10 mg
    Plus some amino acids (Tyrosine, cysteine, methionine and taurine) plus small doses of some vitamins.

    I take 3X daily.

    I also take 2 X 500 mg Thorne L-Tyrosine.

    I guess its time for a retest of the thyroid to see it the iodine has had any impact. Interestingly my hair analysis at the time showed high selenium.

    I cannot tell you how disappointed I was to have the thyroid results come in at normal as at least it would be something to target and treat!

    Thanks
     
  18. Pea

    Pea Senior Member

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    Brain fog - make sure you are getting enough magnesium!
     
  19. Freddd

    Freddd Senior Member

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    Hi Topaz,

    Part of the problem is a vast scarcity of information on this topic. There were several Japanese trials with 50mg/day doses with MS and ALS. MS and ALS both have the similar low cerebral spinal fluid cobalamin level as has been found in CFS and FMS. There were also studies involving intentionally damaged rats with crushed sciatic nerves. What was found in that was that when mb12 was increased to a high enough level, neurological healing was "upregulated". Rich has been using "forced" in place of "upregulated". Then when the central neurological functional improvements took place in the 50mg studies, they hypothecized that the same "upregulated" healing was occurring. However, the studies were not maintained long enough to see what healing might have taken place. What I have found in myself is that things that appeared to heal fully over a year or more, at least a few practioners have said 5 years is required for healing to be maintained, and that these things that appear to complete healing don't fall back rapidly.

    I haven't seen any info on how cobalamin normally crosses the BBB so how it is impaired appears unknown. ALso, based on the intrathecal injections the speed at which cobalamin exits the CSF is also a sizable variable.

    I found the 50mg doses of adb12 and mb12, each and both made noticable differences in brain fog. I found that once a week of adb12 50mg was quite sufficient to maintain equilibrium but that I needed 3 doses a day of mb12 to maintain equilibrium. That was what really determined that I needed injections, 50mg 3x per day just isn't practical on sublinguals. The injection of same quality mb12 (10mg sc injection) provided same results as the 50mg sublingual.
     
  20. L'engle

    L'engle moogle

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    I'm taking 20-25mg AOR methyl b12 now. My brain fog is about the same as when I was taking 45mg. I haven't considered injections yet, but I am still looking into how to increase my brain's number of 'working hours', as all these hours where the brain is 'awake' but not 'on' are very debilitating! Increasing magnesium intake has improved the brain fog another small amount over top of the methyl B12 alone. L carntine fumarate has a good effect on body symptoms but seems to offer no improvement in brain fog for me. Still sorting out ways to improve my protocol!
     

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