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B12 inhibits Retroviruses

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by garcia, Feb 2, 2010.

  1. garcia

    garcia Aristocrat Extraordinaire

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    Inhibition of productive human immunodeficiency virus-1 infection by cobalamins

    Various cobalamins act as important enzyme cofactors and modulate cellular function. We investigated cobalamins for their abilities to modify productive human immunodeficiency virus-1 (HIV-1) infection of hematopoietic cells in vitro. We show that hydroxocobalamin (OH-Cbl), methylcobalamin (Me-Cbl), and adenosylcobalamin Ado-Cbl (Ado-Cbl) inhibit HIV-1 infection of normal human blood monocytes and lymphocytes. The inhibitory effects were noted when analyzing the monocytotropic strains HIV-1-BaL and HIV-1-ADA as well as the lymphocytotropic strain HIV-1-LAI. Cobalamins did not modify binding of gp120 to CD4 or block early steps in viral life cycle, inhibit reverse transcriptase, inhibit induction of HIV-1 expression from cells with established or latent infection, or modify monocyte interferon-alpha production. Because of the ability to achieve high blood and tissue levels of cobalamins in vivo and the general lack of toxicity, cobalamins should be considered as potentially useful agents for the treatment of HIV-1 infection.

    Cobalamin Inhibition of HIV-1 Integrase and Integration of HIV-1 DNA into Cellular DNA


    Our prior studies showed that certain cobalamins inhibit productive HIV-1 infection of primary cultures of blood lymphocytes and monocytes. We demonstrate here that this antiviral activity may be mediated by an inhibition of HIV-1 integrase, an enzyme required for productive infection. Purified recombinant HIV-1 integrase activity was inhibitedin vitroby hydroxocobalamin (OH-Cbl), methylcobalamin (Me-Cbl), adenosylcobalamin (Ado-Cbl), and dicyanocobinamide (CN2-Cbi) with IC50values of approximately 17, 17, 17, and 4 μM, respectively. The agents inhibited HIV-1 infection of cultured monocytes (IC50values for OH-Cbl, Me-Cbl, Ado-Cbl, and CN2-Cbi of 6, 7, 4, and 1 μM, respectively) and of cultured lymphocytes (IC50values of 60, 50, 60, and 11 μM, respectively). Experiments using cultured monocytes or lymphocytes demonstrated that OH-Cbl inhibited integration of HIV-1 DNA into cellular DNA. Thus, cobalamins and cobinamides represent novel inhibitors of HIV-1 integrase. These or related agents may be useful as anti-viral treatments that target HIV-1 integrase.
  2. Hysterical Woman

    Hysterical Woman Senior Member

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    Interesting garcia - cool. Where did you find this?

    Thanks for posting,

    HW
  3. jewel

    jewel Senior Member

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    This is fascinating! Thank you for posting! J.
  4. JT1024

    JT1024 Senior Member

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    By clicking on the titles (they are links):

    The first is from the Journal Blood Volume 86, Issue 4, pp. 1281-1287, 08/15/1995
    Copyright 1995 by The American Society of Hematology

    The second is from: Biochemical and Biophysical Research Communications
    Volume 246, Issue 2, 19 May 1998, Pages 393-397

    You may already know the answer but I thought I could help!

    Julie
  5. garcia

    garcia Aristocrat Extraordinaire

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    Hi maxine,
    the first one someone posted on another list, and the second one I found whilst googling for the first one. The titles are clickable. The first paper is available online for free by following the link.
  6. Hysterical Woman

    Hysterical Woman Senior Member

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  7. Sunday

    Sunday Senior Member

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    My thanks, too.
  8. Carrigon

    Carrigon Senior Member

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    I think I do notice an increase in energy when I take B vitamins, but for me, I've never been able to stay on them because they seem to make my acid reflux alot worse. But the few times I've been able to do it, I do think there was an energy increase.
  9. FernRhizome

    FernRhizome Senior Member

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    My B12 levels are always unnaturally high even when I am not taking B12 at all, even after years of not taking it.....I heard that sometimes gut problems can cause a high B12. At any rate when I did take B12 many years ago, injections & oral, it sometimes helped slightly but then would stop helping & make me worse...very confusing results in my case. ~Fern
  10. richvank

    richvank Senior Member

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    Hi, Fern.

    High serum B12 levels suggest that the body is not able to use B12 effectively. This is common in CFS. The best way to determine whether B12 is functionally deficient is to run a urine organic acids test that includes urine methylmalonic acid, such as the Genova Diagnostics Metabolic Analysis Profile. This is available from some doctors, or you can order it directly without a doctor's order from www.directlabs.com. If methylmalonic acid is elevated in this panel, it indicates that B12 is functionally deficient. If, in addition, Figlu (formiminoglutamic acid) is elevated on this same panel, it is very likely that there is a partial block in the methylation cycle, which requires B12 function as well. Most PWCs appear to have this partial block. The treatment for it includes a form of B12, but it is taken together with an active form of folate (5-methyl tetrahydrofolate, aka FolaPro or Metafolin). B12 alone is not able to correct this problem, though in some cases it gives temporary help.

    A more direct panel to test the methylation cycle, the folate metabolism and the glutathione status (which are linked together biochemically and which all appear to show abnormalities in most cases of CFS) is the Vitamin Diagnostics methylation pathways panel. The contact information for this panel is below. This lab is currently finishing a move to a new building, and is not yet up to full operation, but hopefully will be soon.

    The reason B12 runs high in the serum in CFS, in my hypothesis, is that the cells of the body import B12 but are not able to utilize it because of glutathione depletion and a partial methylation cycle block. They therefore bind it to haptocorrin and export it to the blood. Most of the B12 in the blood, even in normal, healthy people, is in this form, and is not available to the cells in general. Normally, this form stays in the blood a few days, and is then imported into the liver cells. Some is stored and some is exported in the bile to the gut, where it has another chance to be absorbed and sent to the cells again. This appears to be a salvage and storage pathway for B12, to provide it when times are tough and it isn't coming in much from the diet. But in CFS, too much of it is being recycled this way, because the cells can't use it properly.

    If you want to know more about this, check out the B12 thread (which is horrendously long), or check my papers in the Files section of the Yahoo cfs_yasko group's website at http://health.groups.yahoo.com/group/CFS_Yasko/

    Best regards,

    Rich

    Methylation Pathways Panel

    This panel will indicate whether a person has a partial methylation cycle block and/or glutathione depletion. I recommend that this panel be run before deciding whether to consider treatment for lifting the methylation cycle block. I am not associated with the lab that offers this panel.

    The panel costs $300 and requires an order from a physician or a chiropractor. The best way to order the panel is by fax, on your clinician’s letterhead.


    Available from:

    Vitamin Diagnostics, Inc.
    540 Bordentown Avenue
    South Amboy, NJ 08879
    USA
    Phone:+1 (732) 721-1234


    Lab Director: Tapan Audhya, Ph.D.
    (usually at the lab on Tues. and Wed. from 1 to 3 p.m., Eastern time)

    Dr. Audhya is willing to help clinicians with interpretation of the panel by phone.
  11. garcia

    garcia Aristocrat Extraordinaire

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    Fern, was going to post a reply, then saw Rich's great response. Nothing much I can add to that!

    Except to say I was also very very high on the standard B12 test (twice off the range or something). Far from indicating B12-sufficiency, it was actually indicating B12 deficiency for me. I do really well on B12 now.
  12. Sunday

    Sunday Senior Member

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    Very interesting stuff! Thank you. I'm already on the active B12s, and it's nice to know they're doing even more than I thought!
  13. froufox

    froufox Senior Member

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    My experience is identical to Garcia's - the last few times that I have been tested for B12 (just a regular NHS serum test) my levels are way over the range (folic acid was the same) but in my case it was a reflection of a more severe functional deficiency compared to when my levels were just in the normal range. I know this for sure because it was a true reflection of how I felt....since my blood levels increased according to the standard NHS test...in other words the higher blood levels definitely correlated with me feeling worse both mentally & physically. This definitely fits in with Rich's explanation.

    It also just shows once again how inadequate and misleading regular tests can be and how ignorant GPs are in these matters!

    Not surprisingly I also have a marked response to b12 supplementation, notably methylb12 - it either it makes me feel really good or it can induce detox too quickly so I have to be careful not to overdose but it is quite clear that I need the stuff.
  14. natasa778

    natasa778 Senior Member

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    Blood. 1995 Aug 15;86(4):1281-7.
    Inhibition of productive human immunodeficiency virus-1 infection by cobalamins.
    Weinberg JB, Sauls DL, Misukonis MA, Shugars DC.Department of Medicine, VA Medical Center, Durham, NC 27705, USA.
    Various cobalamins act as important enzyme cofactors and modulate cellular function. We investigated cobalamins for their abilities to modify productive human immunodeficiency virus-1 (HIV-1) infection of hematopoietic cells in vitro. We show that hydroxocobalamin (OH-Cbl), methylcobalamin (Me-Cbl), and adenosylcobalamin Ado-Cbl (Ado-Cbl) inhibit HIV-1 infection of normal human blood monocytes and lymphocytes. The inhibitory effects were noted when analyzing the monocytotropic strains HIV-1-BaL and HIV-1-ADA as well as the lymphocytotropic strain HIV-1-LAI. Cobalamins did not modify binding of gp120 to CD4 or block early steps in viral life cycle, inhibit reverse transcriptase, inhibit induction of HIV-1 expression from cells with established or latent infection, or modify monocyte interferon-alpha production. Because of the ability to achieve high blood and tissue levels of cobalamins in vivo and the general lack of toxicity, cobalamins should be considered as potentially useful agents for the treatment of HIV-1 infection. Publication Types: PMID: 7632933

    Full text article http://bloodjournal.hematologylibrary.org/cgi/reprint/86/4/1281



    Med Hypotheses. 1993 Feb;40(2):93-4.
    A novel antiviral strategy for HIV infection.
    May BA.
    The replication of human immunodeficiency virus (HIV) may be modulated in part by host factors such as DNA methylation. Hypermethylation of the HIV provirus may suppress viral replication and play a role in the establishment of latency. HIV seropositive individuals have decreased levels of metabolites involved in methylation. It is proposed that metabolites such as S-adenosylmethionine (SAM), methylcobalamin and methyltetrahydrofolate be explored as potential therapeutic agents in HIV infected individuals. PMID: 8455481


    Biochem Biophys Res Commun. 1998 May 19;246(2):393-7.

    Cobalamin inhibition of HIV-1 integrase and integration of HIV-1 DNA into cellular DNA.

    Weinberg JB, Shugars DC, Sherman PA, Sauls DL, Fyfe JA. VA Medical Center, Durham, North Carolina 27705, USA.

    Our prior studies showed that certain cobalamins inhibit productive HIV-1 infection of primary cultures of blood lymphocytes and monocytes. We demonstrate here that this antiviral activity may be mediated by an inhibition of HIV-1 integrase, an enzyme required for productive infection. Purified recombinant HIV-1 integrase activity was inhibited in vitro by hydroxocobalamin (OH-Cbl), methylcobalamin (Me-Cbl), adenosylcobalamin (Ado-Cbl), and dicyanocobinamide (CN2-Cbi) with IC50 values of approximately 17, 17, 17, and 4 microM, respectively. The agents inhibited HIV-1 infection of cultured monocytes (IC50 values for OH-Cbl, Me-Cbl, Ado-Cbl, and CN2-Cbi of 6, 7, 4, and 1 microM, respectively) and of cultured lymphocytes (IC50 values of 60, 50, 60, and 11 microM, respectively). Experiments using cultured monocytes or lymphocytes demonstrated that OH-Cbl inhibited integration of HIV-1 DNA into cellular DNA. Thus, cobalamins and cobinamides represent novel inhibitors of HIV-1 integrase. These or related agents may be useful as anti-viral treatments that target HIV-1 integrase.

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