Question on antiviral effect of nitric oxide and B12 Dr. Cheney

Discussion in 'Fibromyalgia and ME & Chronic Fatigue Syndrome' started by meganp, Oct 5, 2008.

  1. meganp

    meganp New Member

    I understand that a number of CFS doctors are prescribing high doses of vitamin B12, supposedly to remove the toxic nitric oxide in our bodies, and often at the same time prescribing antivirals such as Valcyte or Nexavir.

    It is with great astonishment then, that after considerable reading of articles on the Pubmed database and other websites, that there seems to be considerable evidence that nitric oxide is itself an antiviral produced by the body's immune system in response to infection. This leaves me with the question then of why we would want to remove it if we are following an antiviral treatment?

    Do any patients of Cheney or Kenny De Mielier (or other CFS doctors) have any idea of how these doctors would respond to this question?

    One example of an article is as follows:
    http://www.ncbi.nlm.nih.gov/pubmed/15479821?ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

    A search in pubmed using the combination or 'nitric oxide HSV', 'nitric oxide EBV' or 'nitric oxide herpes' will reveal countless such articles, although there does not seem to be much on HHV6.

    I am taking B12 injections myself at the moment in line with my doctors advice, but am not yet taking antivirals - though am considering them (but now wonder if I should stop the B12?).

    Megan (very puzzled).
  2. heapsreal

    heapsreal New Member

    Its my understanding that nitric oxide produces peroxynitrate which is an oxidative substance and b12 acts on this not necessarily nitric oxide. Have also read that the Amino acid arginine produces nitric oxide and is used as an immune stimulant, i think it is the byproduct of this that is no good and or people with cfs cant eliminate it properly. B12 also act as an antioxidant seperate to its effects on peroxynitrate and helps protect the myelin sheaths around nerves etc that can be damaged by viruses like ebv, chicken pox, hhv6 etc. i think sometimes nitric oxide is used interchangably with peroxynitrate which it shouldnt.
    I have just pulled this info out the back of my brain after a few years of studying cfs etc, so please dont quote me,
    ta
  3. richvank

    richvank New Member

    Hi, Megan.

    I would like to comment on the use of vitamin B12 in the treatment of CFS. First, some background:

    1. The use of high dosage intramuscular B12 injections in CFS was pioneered by Drs. Paul Cheney and Charles Lapp in the 1990s. They found that significant fractions of PWCs had high homocysteine, high methylmalonate, or both, suggesting low functional B12. They found considerable symptomatic improvement was produced by dosages above 2,000 to 2,500 micrograms per injection. They initially started with cyanocobalamin, but later Dr. Cheney began to advocate use of hydroxocobalamin, and the dosages went quite a bit higher.

    2. Evengard et al. and Regland et al. in Sweden found in the 1990s that significant fractions of the PWCs they studied had low B12 in their cerebrospinal fluid, and Regland et al. also found elevated homocysteine in the cerebrospinal fluid.

    3. Regland et al. in 1998 found that hydroxocobalamin injections were significantly more beneficial in the patients who did not have the most common polymorphism in their MTHFR enzyme. This suggested that the supplemental B12 was acting at methionine synthase in the methylation cycle, but this was not really appreciated or understood by the CFS research and clinical community at that time (including me). Tragically, we all "missed the boat" at that time and lost a few years in figuring out CFS.

    4. Dr. Cheney went on to suggest in 1999 that the B12 was acting to detoxify the brain, since it is known that B12 will bind several known toxins, including cyanide.

    5. Prof. Martin Pall suggested in 2001 that the B12 was binding to nitric oxide, and blocking what he called the NO-ONOO cycle, which he hypothesized to be responsible for the pathogenesis of B12. He continues to maintain today that this is the role of high-dose B12 in the treatment of CFS.

    6. In the early 2000 decade, the doctors on the DAN! project began using methylcobalamin injections in autistic children, and found them to be beneficial.

    7. In 2004, Jill James et al. published a landmark paper in autism research in which they showed that there is a partial block at methionine synthase and a depletion of glutathione in autism, and that treatment with the combination of methylcobalamin, betaine, and folinic acid would lift this block and would restore the level of glutathione.

    8. When I read their paper in Dec. of 2004, it dawned on me that the same biochemical problem must be present in CFS as in autism, since glutathione depletion is a factor in CFS also, and directly supplementing it doesn't restore it to normal. I eventually realized that the work of Regland et al. back in 1998 was pointing toward methionine synthase as the core issue, too. This caused me to begin encouraging PWCs to consider trying the treatments in use by the DAN! project in autism. There was some partial success. I then learned about the approach of Dr. Amy Yasko, also primarily in autism, and I encouraged PWCs to try her treatment approach. Several have done so. However, it is rather complex and expensive. With the help of one of the PWCs who is following this treatment approach (and who posts to this board), I extracted the essential part of the Yasko treatment, which eventually was reduced to 5 nutritional supplements. One of them is sublingual hydroxocobalamin, and two others are active forms of folate (folinic acid and 5-methyltetrahydrofolate aka FolaPro or Metafolin). I called this the "simplified treatment approach." If you want to read about this, check my post of July 18, 2007. At present, at least several hundred PWCs worldwide are using this treatment, including quite a few who post to this board. There are several clinicians using it in their practices. A research study of this treatment is currently underway on 30 women in Springfield, MO, by Dr. Neil Nathan, and the initial results are very encouraging.

    9. Based on all of this, my hypothesis is that the main action of B12 in the treatment of CFS is to provide more methylcobalamin to support methionine synthase and lift the partial methylation cycle block. The folates are important for this enzyme also, and that's why Regland et al. found the MTHFR enzyme polymorphism to affect the treatment. In the Yasko treatment and the simplified treatment approach, this problem is handled by bypassing the MTHFR reaction completely by using FolaPro.

    10. So the bottom line is that hydroxocobalamin does bind toxins, including nitric oxide, cyanide, sulfite, and mercury, as well as many others but these reactions function mainly to deplete the amount of B12 that can support methionine synthase, which is the most important function of B12. The presence of these competing toxins and the absence of sufficient protection of B12 (because of glutathione depletion) are the reasons such high dosages of B12 are needed to see an effect of treatment.

    11. You asked how some of the principal CFS physicians would answer your question about why nitric oxide should be removed in the treatment of CFS. I can't speak for them, but I can tell you that I am in communication with them, and I would say that their views appear to be shifting, based on results of treatment using combined B12 and bioactive folates.

    Rich