1. Patients launch a $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
Patient Experience: "What Bronllys taught me about pacing."
In 2012, Maya, who had tried to cope with ME/CFS on her own for many years, attended a pain management centre in Wales, U.K., and is now able to achieve more through pacing and acceptance, than she had been able to before the course...
Discuss the article on the Forums.

DR. Vank The VDR changes?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by greenshots, Aug 11, 2012.

  1. greenshots

    greenshots Senior Member

    Messages:
    399
    Likes:
    136
    California
    I got this from Yasko's forum. Seems she's changing things around because of the controversy over things? If this isn't typical Yasko I don't know what is. A huge, complicated answer that still really doesn't give you an answer. Dr. Vank, can you make heads or tails of this? I have a friend who got her results last month and has no idea if its + or - or whats what? It would help if she'd just say she doesn't have all the answers but for now, we can read this as positive or that as negative.

    Thank you,
    Angela



    VDR information:

    Recently there has been a barrage of questions related to VDR. The situation with respect to VDR is highly complex which is why I have not tried to thoroughly explain it in the past. I have tried to keep it simple for you and note the observed clinical relationship between those who cannot tolerate higher levels of methyl donors (tt) and those that can handle more methyl donors (TT) in terms of their Taq status. Based on the volume of questions and confusion regarding VDR I will go ahead and explain the complexity of the situation.

    I believe this recent flurry of interest in the genotype designations for the VDR is related to of the use of GcMAF. While initially it was thought that the VDR SNP data played a role in determining the use of that agent, it has since been suggested that simply the use of Vitamin D may be a help. As such this focus on VDR may not be necessary. I had reached a similar conclusion with regard to vitamin D for my program a while ago with the additional caveat that I feel support for the receptors is also important. The bottom line is that I do feel vitamin D support is a positive, and the use of rosemary, sage and resveratrol can also help support healthy vitamin D levels.

    First a quick point of nomenclature before I go in to the complexity of the situation. In general the presence of the restriction site is denoted by a lower case letter and the polymorphism that eliminates the site is denoted by an upper case letter. The situation is more complex in that the Bsm and Taq sites have an inverse relationship. To add to the confusion, studies have found decreased levels of VDR protein with Bsm BB and Taq tt genotypes compared to other genotypes yet vitamin D levels were significantly increased at the same time that levels of VDR protein were significantly decreased. Thus increased 1,25(OH)2 D3 levels, might lead to downregulation of VDR expression. Decreased VDR levels could result in defective VDR signaling.( JOURNAL CLINICAL IMMUNOLOGY Volume 29, Number 4 (2009), 470-478 )

    The situation with Fok is also complex as the polymorphism (FF, loss of site) actually leads to the production of a protein with increased activity. The Fok SNP, situated in exon 2, gives rise to an alteration in the start codon position resulting in a 3 amino acid longer protein produced by the F allele. So the Fok site affects the protein directly such that those who are missing the restriction site (FF) make a shorter protein, but one that is actually more active. While those who do not have a ‘mutation’ and have the restriction site actually make the full length protein but it has less activity.(Nutrition Reviews, What Are the Frequency, Distribution, and Functional Effects of Vitamin D Receptor Polymorphisms as Related toCancer Risk?Nicholas J. Rukin August 2007(II): S96 –S101Vol. 65, No. 8). In conclusion, the Fok polymorphism yields a 424 VDR variant somewhat more active than the 427 variant in terms of its transactivation capacity as a transcription factor. (Uitterlinden et al. / Gene 338 (2004) 143–156)

    The Taq and Bsm situation is even more complicated. Both are in a regulatory portion of the protein and the SNP changes do not affect the protein per se but they both affect a regulatory string of A’s in the sequence. Thus the presence or absence of the Bsm and Taq sites affects the number of A’s in the protein. Since Bsm and Taq have inverse effects both Bt and bT impact the number of A’s. The number of A’s in turn affects the stability of the information to make the VDR protein. As with everything else related to VDR, there is disagreement whether the shorter stretch of A’s (Bt) or the longer stretch of A’s (bT) grants more stability to the protein. Reports regarding which genotype is associated with a range of diseases or health conditions vary depending on the researcher.
    To try to keep things clear, in the future we will use the tt or TT designation to denote VDR Taq and FF and ff for Fok. Those who are tt should consider limited methyl donors. Those who are TT tend to have a greater tolerance for ie methylB12.

    Again, the bottom line is that I do feel low dose vitamin D plus rosemary and sage and resveratrol are a positive for all. This is especially true as there is conflicting literature regarding disease susceptibility and the various VDR SNPS that at times is totally contradictory.
    xrunner likes this.
  2. xrunner

    xrunner Senior Member

    Messages:
    476
    Likes:
    132
    Thanks for posting this Angela. It may have answered something I was asking myself these days.

    However, I read it three times and I'm not sure I understand it all.

    Questions:
    Is she saying that VDR genes are not significant because of conflicting studies on vitamin D metabolism?

    Is vitamin D supplementation more important than any VDR polymorphism? vitamin D making GcMAF working better?

    Does she suggest resveratrol, sage and rosemary as a way to enhance VDR activity?


    I personally noticed that when I add resveratrol and susnhine (Vit D) to the maf I get a much more pronounced effect from the maf, much more than from maf and D alone.
  3. Sparrow

    Sparrow Senior Member

    Messages:
    660
    Likes:
    746
    Canada
    As far as I can get from a quick skim through what's written there:

    She doesn't seem to be changing anything she's said about the VDR genes before, more just explaining why she isn't confident about saying anything about them beyond that.

    She is not necessarily saying that VDR genes are insignificant, just that they don't always provide straightforward simple effects, because there are many different factors involved (whereas for some other gene mutations, the effect might be very clear and predictable). Their effects may also be influenced by vitamin D levels themselves. And she summarizes that not enough research has been done yet to tell for sure whether or how the VDR genes impact people getting diseases (since so far the results of the studies that have been done haven't had consistent results). She does still feel VDR taq is a good indicator for a person's ability to tolerate methyl groups.

    She is suggesting that vitamin D itself might be of greater significance in whether GcMAF will work better, rather than the VDR genes (for a while, some people suspected that you could tell how well you'd respond by checking your VDR genes).

    She is suggesting resveratrol, sage, and rosemary to help with maintaining healthy vitamin D levels.
    xrunner likes this.
  4. greenshots

    greenshots Senior Member

    Messages:
    399
    Likes:
    136
    California
    what Sparrow says makes alotta sense. Also It looks like the VDR taq should read TT is ++ since having the defect has meant more methyls are needed where the VDR Taq tt should be - - since not having a defect means less methyls.

    I still can't make sense of the Fok but it looks like at least one little f might be a defect if you base it on what she says. But who knows?
  5. greenshots

    greenshots Senior Member

    Messages:
    399
    Likes:
    136
    California
    Ok, I think I have the VDR Taq down. The old version was ++ when you needed alotta methyl donors so in this new version the VDR taq TT is a full mutation and you need methyl donors. The tt should be normal, needing less. I was able to compare my husband's with my kid's and two other friends who have them (mine are all whacked so can't compare) and they either have normal or partials so the results were there.

    The Fok I have no idea about since she didn't use ff or FF for ours but my sister has her gene follow up in 2 weeks & I'll know for sure then. I'll update then.
  6. greenshots

    greenshots Senior Member

    Messages:
    399
    Likes:
    136
    California
    The results are in and it looks like having the ff, a downregulation, is a defect but the FF is norml for the VDR FOK. My doc says this flys in the face of what most researchers think but she felt that when it comes down to it, its all about poor pancreatic function.

    The VDR Taq is pretty much the same as above with its TT is a full mutation vs. tt which is no mutation since its really about how many methyl donors you can take. The defect means you tolerate them but the normal reading means you can't have as many.

See more popular forum discussions.

Share This Page