Severe ME Day of Understanding and Remembrance: Aug. 8, 2017
Determined to paper the Internet with articles about ME, Jody Smith brings some additional focus to Severe Myalgic Encephalomyelitis Day of Understanding and Remembrance on Aug. 8, 2017 ...
Discuss the article on the Forums.

Patent: Method for Treating or Preventing a Functional Vitamin B12 Deficiency

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by adreno, Apr 13, 2012.

  1. adreno

    adreno PR activist

    Messages:
    4,843
    Likes:
    11,028
    Abstract:

    A method and medical composition for the treatment and/or prevention of a functional Vitamin B12 deficiency in an individual that is brought about as a consequence of oxidative stress on biochemical pathways. The functional Vitamin B12 deficiency may eventually present as dementia, other neuropsychiatric abnormality and/or vascular disease. The method involves the administration of a medical composition that supplies a cobalt-sulphur bond in the upper ?-ligand of an intracellular cobalamin molecule thereby facilitating intracellular processing of cobalamin. The cobalt-sulphur bond may he provided directly by administration of a thiolatocohalamin, such as glutathianyl-cobalamin or indirectly by the co-administration of Vitamin B12 (or a derivative thereof) with a sulphur-containing molecule, such as glutathione or a precursor thereof.
    http://www.faqs.org/patents/app/20110077194
     
  2. adreno

    adreno PR activist

    Messages:
    4,843
    Likes:
    11,028
    A novel role for vitamin B(12): Cobalamins are intracellular antioxidants in vitro.

    Free Radic Biol Med. 2009 Jul 15;47(2):184-8. Epub 2009 May 3.
    Affiliation

    Abstract

    Oxidative stress is a feature of many chronic inflammatory diseases. Such diseases are associated with up-regulation of a vitamin B(12) (cobalamin) blood transport protein and its membrane receptor, suggesting a link between cobalamin and the cellular response to inflammation. The ability of cobalamin to regulate inflammatory cytokines suggests that it may have antioxidative properties. Here we show that cobalamins, including the novel thiolatocobalamins N-acetyl-l-cysteinylcobalamin and glutathionylcobalamin, are remarkably effective antioxidants in vitro. We also show that thiolatocobalamins have superior efficacy compared with other cobalamin forms, other cobalamins in combination with N-acetyl-l-cysteine (NAC) or glutathione (GSH), and NAC or GSH alone. Pretreatment of Sk-Hep-1 cells with thiolatocobalamins afforded robust protection (>90% cell survival) against exposure to 30 microM concentrations of the pro-oxidants homocysteine and hydrogen peroxide. The compounds inhibited intracellular peroxide production, maintained intracellular glutathione levels, and prevented apoptotic and necrotic cell death. Moreover, thiolatocobalamins are remarkably nontoxic in vitro at supraphysiological concentrations (>2 mM). Our results demonstrate that thiolatocobalamins act as powerful but benign antioxidants at pharmacological concentrations. Because inflammatory oxidative stress is a component of many conditions, including atherosclerosis, dementia, and trauma, their utility in treating such disorders merits further investigation.

    PMID 19409980

    Full text:
    http://www.brasch-group.com/pdf/Birch et al (2009) FRBM.pdf

    From the full text:

    "The nonthiolatocobalamins cyanocobalamin (CNCbl), hydroxocobalamin (HOCbl), and MeCbl were least effective at protecting against Hcy induced death; their optimized concentrations of 12.517.5?M provided?30% protection. At these concentrations, thiolatocobalamins afforded greater than 80% protection".
     
  3. maryb

    maryb iherb code TAK122

    Messages:
    3,512
    Likes:
    3,096
    UK
    Can someone explain this simply to a foggy brain??
     
  4. nanonug

    nanonug Senior Member

    Messages:
    1,250
    Likes:
    422
    Virginia, USA
    Usually, cobalamin is protected in the cell by glutathione, in the form of glutathionylcobalamin. In cases of persistent oxidative stress, glutathione gets depleted and cobalamin loses its protection, resulting in oxidised cobalamin. Oxidized cobalamin (vitamin B12) doesn't work leading to a functional deficiency. This is at the heart of richvank glutathione depletion/methyl cycle block hypothesis for ME/CFS.

    Here's an article with some additional info:

    "Cobalamin in inflammation III glutathionylcobalamin and methylcobalamin/adenosylcobalamin coenzymes: the sword in the stone? How cobalamin may directly regulate the nitric oxide synthases"
     
  5. justy

    justy Donate Advocate Demonstrate

    Messages:
    5,310
    Likes:
    12,094
    U.K
    Sorry i dont fully understand what is the patent actually for? Who is it that has applied for this patent/ made this discovery?
    Thanks, Justy.
     
  6. adreno

    adreno PR activist

    Messages:
    4,843
    Likes:
    11,028
    "Inventors: Andrew Mccaddon (Wrexham, GB)".
     
  7. adreno

    adreno PR activist

    Messages:
    4,843
    Likes:
    11,028
    Another interesting question: is it possible to get our hands on some thiolatocobalamin, or somehow optimize its synthesis?

    In the patent application, they recommend using a glutathione precursor, along with B12.

    In the study I quoted, B12 plus NAC was indeed more effective than B12 alone, but NAC on its own was actually even more effective. I don't quite know what to make of it.
     
    alex3619 and nandixon like this.
  8. Valentijn

    Valentijn Senior Member

    Messages:
    14,281
    Likes:
    45,822
    It's just a patent, and is completely meaningless at this point. All it means is that someone has a theory or wild guess and wants to claim rights to it before anyone else does. People patent random stuff all the time, and never follow up on developing it.
     
  9. adreno

    adreno PR activist

    Messages:
    4,843
    Likes:
    11,028
    It doesn't change the fact that thiolatocobalamins are vastly more effective at protecting cells than regular forms of cobalamin.

    Anyway, I found it curious that someone is patenting treating a B12 deficiency.
     
  10. maryb

    maryb iherb code TAK122

    Messages:
    3,512
    Likes:
    3,096
    UK
    Thanks nanonug:)
     
  11. Little Bluestem

    Little Bluestem All Good Things Must Come to an End

    Messages:
    4,666
    Likes:
    5,488
    Is MeCbl methylcobalamin?
     
  12. adreno

    adreno PR activist

    Messages:
    4,843
    Likes:
    11,028
    Yes it is. And Hcy is homocysteine.
     
    Little Bluestem likes this.
  13. Freddd

    Freddd Senior Member

    Messages:
    4,941
    Likes:
    1,476
    Salt Lake City
    Hi Justy,

    There are thousands of these patent applications. Somebody spends all day filing patent applications based on optimistic reading of everybody else's research just in case anything actually works. Every form of cobalamin anybody has researched in every possible combination with anything and everything has been patented so that the persons behind it can make billions while the actual discoverer gets the shaft.
     
    Lotus97, Little Bluestem and justy like this.
  14. nandixon

    nandixon Senior Member

    Messages:
    832
    Likes:
    2,083
    Hi Adreno,

    I also came across the same reference you originally posted, and another related dozen or so patents, patent applications and research articles that the Brasch group and their collaborators such as McCaddon and Quadros have written. (http://www.brasch-group.com/research/vitamin-b12)

    I definitely think this is worth testing. It may be that for a subset of people with CFS/ ME, using a preformed thiolactocobalamin such as glutathionylcobalamin or N-acetyl cysteinylcobalamin, might be a better form of vitamin B12. It could give entirely different results than using an ordinary B12 (Ado-, Me- or HO-) with separately supplemented glutathione, for example, which can be bad for some people.

    The two patents that give details for the synthesis of the thiolactocobalamins are here:

    http://www.patentstorm.us/patents/7777046/fulltext.html

    http://www.patentstorm.us/patents/7030105/fulltext.html

    The syntheses are actually very simple - in a laboratory anyway, and we might be able to do a sort of poor man's version at home (I used to be an organic chemist). Hydroxocobalamin ideally needs to first be converted to its equilibrium aquacobalamin form in water using an acid like acetic acid (vinegar) or maybe citric acid (lime or lemon juice) or ascorbic acid (vitamin C). A solution of a slight excess of either glutathione (GSH) or N-acetyl cysteine (NAC) in water (or possibly just as their dry powdered forms) is then added to the aquacobalamin. The tricky issues are trying to keep to a minimum the oxidation of GSH or NAC to their disulfide forms by the action of aquacobalamin, and the destruction of aquacobalamin by excess (reduced) GSH/NAC. The authors of the patents overcome this by using very concentrated solutions or slurries of the reactants (aquacobalamin, & GSH or NAC), and by adding the small excess of GSH or NAC to the aquacobalamin slowly dropwise. Also, since aqueous solutions of thiolactocobalamins are sensitive to light (just like methylcobalamin and adenosylcobalamin), they run the reactions in the dark.

    Since only slightly acidic conditions are used, I think it's conceivable a little thiolactocobalamin could be made, in a very crude way, by simply placing a little (less than 5mg) GSH or NAC under a person's tongue and then adding several drops of Mega Hydroxy-B12 on top of that and doing a sort of in situ sublingual thing. May depend on what sort of fillers are present in the capsules of GSH/NAC (stearic and citric acid might be ok and even helpful; basic/alkaline filler may need to be neutralized).

    I've ordered some GSH and NAC and am going to play around with the idea some. The Brasch group might be willing to sell some of their material as well. There's not very much commercial availability of these thiolactocobalamins right now, it seems. (Note that these patents are only violated if the products are precipitated from solution and isolated as solids. :))
     
    place, alex3619 and adreno like this.
  15. adreno

    adreno PR activist

    Messages:
    4,843
    Likes:
    11,028
    Hi nandixon, I totally missed your post until now. Your idea sounds very interesting! Did you ever try it out?
     

See more popular forum discussions.

Share This Page