VDR Vitamin D and Lyme

I have never seen any literature on that. I have looked into the Marshall Protocol and I do think they are on to something. I think they are wrong about their conclusions and treatments, but my instincts are telling me there is something to it. I have no references to back that up so it is total speculation. I'm not sure why I think that.

IMO, it is the amount of oxidative stress that determines epigenetic shifts on genes. Oxidative stress is determined by our microbiome and Borrelia is a significant factor in oxidative stress. Not from direct toxins IMO, but because of the bacterial growth that happens when it is present.

hi Georgia

yes, i too believe there is something to the Marshall theory on VDR and lyme - that's, why i would be interested to see if it is actually suppressed/downregulated by 50x as that, is a huge number = most other bacteria that can cause downregulation have only been found to do so by factors of 3-5.

yep - that was the paper i saw referenced most =- but others random ones also
however there is no mention of the VDR in it - there are charts of genes that are downregulated and upregulated - perhaps i am just too ignorant of genetics to spot which is the VDR gene - or perhaps the gene that is downregulated is some steps away in the chain from the VDR and teh claim is misleading / overstated - in that they assume because the upstream gene is downregulated - then so is the VDR expression

i think Marshal has hold of some part of the puzzle - but I don't think the best way through can be 1-4years to v restrictive treatment....light avoidance, no vit D in the diet etc

but it does seem to me like almost everything that helps - first causes herx - and only afterward do you get improvement - something that would fit with removing the brakes of the immune system.

i wonder if we will find in due course that many of the herbs used by people like Buhner - are in fact acting in some way at an epigenetic level by alleviating the VDR block - and restoring some of the innate immune function. (this may not be far fetched as I think the adaptogenic herbs act epigenetically on other systems in the body)

highly significant that the VDR is what is used to help manage homeostasis in the gut microbiome - as just about everyone with Lyme - and especially Bart - have problems there. and this is also where around 70% of our immune system resides - so a huge destabilizing effect on teh whole organism - which is what many of us experience. ALL symptoms flare when gut symptoms flare.

BTW, i have a special interest in this VDR thing, as my own illness and my partners started while taking high dose ( 100,000IU per day for 7 days ) of D3 on the advice of a nutritionist.
if marshall is correct thsi would cause levels of Vitamin D precursor ( 25 D ) to go v high and block the VDR giving intracellular pathogens a free ride,

its a shame we can't seem to validate the 50x less VDR claim

edited to correct my mixup of teh Vitamin D metabolite/precursor

Post Edited (Garzie) : 10/18/2020 1:58:45 PM (GMT-6)

Thank you very much, Dimitry
i had read it and then used the find tool in chrome for VDR and nothing came up - but it is clearly there at the bottom of the table.

so at least in one study Lyme dramatically reduces expression of VDR receptors on cells and hence dramatically interrupted this innate immune pathway.

very interesting.
would certainly fit with my experiences - if we combine the immunosuppressive effect of v high 25 Vitamin D levels (from marshalls theory) with this v high VDR suppression by Lyme.

for instance - if someone were infected with Lyme but their competent immune system was coping - then you dosed heavily with Vit D3 - you could have an immunosuppressed episode - allowing lyme to prosper and then overwhelm your immune system - leading to chronic Lyme.

some gaps exist for sure - so far from proven - but a plausible mechanism - as this happened to both myself and my partner on the same day ( we were both seeing the same nutritionist and on the same Vit D dose)

it's pretty clear we both have Lyme - and had had odd symptoms for around 6month prior to this - but the explanation for why we should both become properly ill on the same day with Lyme was missing.

Post Edited (Garzie) : 10/18/2020 1:59:23 PM (GMT-6)

WBF - i am still undecided about how vitamin D is affecting me now.

there does seem to be evidence that very large doses cause immune suppression - and my doses were 100,000 a day ( due to mistakes in the instructions from the nutritionist ) 5 years ago could well have had a role in my initial illness.

recently (for almost 9 months i think) i have been supplementing with around 5,000IU a day of vitamin D, as its generally needed for immune regulation - and some small trials indicate it could be highly protective of serious effects of COVID - so another reason to ensure levels are at least in the middle of the rang and I have been improving over that time.

5,000IU a day or its equivalent dose averaged out over weeks or months is well within what the body can excrete and so true toxicity is very unlikely indeed.
(in my reading I came across papers saying humans can generate up to something in the region of 20,000IU a day at the equator and if outdoors all day).

however, the VDR blocked by bacterial action hypothesis - if true - puts a slightly different light on this - i am not really at a conclusion with my thinking on this myself at the moment.

the marshall protocol website explains it like this:
++++++++++++++
Although casually referred to as a vitamin by some members of the medical community, molecular biologists have long realized that the precursor form of vitamin D (25-D) is really a secosteroid. Recent molecular modeling research (which has been confirmed by a large amount of clinical data) has shown that levels of 25-D over 20 ng/ml can bind and inactivate the VDR, which subsequently shuts down the innate immune system.

Certain species of bacteria also produce substances that can bind and inactivate the VDR in a manner similar to 25-D. Consequently, people who are infected with the Th1 pathogens and consuming vitamin D are no longer able to produce the AMPs or turn on the innate immune response. This allows their bacteria to proliferate and spread.
++++++++++

so basically, marshall says too much-supplemented vitamin D ( usually referred to in tests as 25 Vitamin D or 25D) and not enough of the active 1-25D made from it in the body, blocks the VDR receptor and nullifies this critical part of the innate immune system ( the bit that deals with small intracellular microbes)

these are the two metabolites that can be tested to see if the balance is out ( i am considering this)

however, as i understand it, even people on the marshall protocol first take the VDR agonist (olmesartan), then reduce vitamin D consumption/production - then finally take ABX - so it seems unblocking the VDR receptors is the key thing.

i am wondering if other courses of action may actually reduce this blocking effect eg things that reduce inflammation, sleep, diet etc - and whether some of the buhner herbs are in fact acting on these pathways.

some plant-derived chemicals are known to act on the VDR receptor for instance - quercetin and curcumin - albeit weekly - the studies also hint at clinical or in vivo effects that are disproportionate to the affinity for the VDR - suggesting some other mechanism is present.

i have a hunch Marshall may be on to something - maybe not all of it - perhaps a nub of something helpful there - but think there needs to be another way through - apart from their current approach.

thanks for the input Dimirty

yes, I had read that various bacteria can decrease VDR expression significantly -
Pseudomonas aeruginosa does the also
and some pathogenic fungi species I think - aspergillus for instance

what I found interesting is the paper we discussed above demonstrated a 50x reduction by exposure to live borrelia - and this is an order of magnitude greater than any of the others i have so far read about.

that is significant to me

interesting idea - thanks Dimitry

actually, i have done the azithromycin (macrolide), Doxycycline ( tetracycline) and rifampicin combo for several months.
I added one at a time starting with doxy - I had herx like symptoms for the first 3-6 weeks after adding each one - then some sustained improvement - but had to stop due to liver enzymes and pain in the liver area after all three for around 4months.

i didn't notice any increased light sensitivity - I gather you mean skin burning/reddening in the sun more easily.

it could have been there - but if it was it wasn't super pronounced.
in the UK strong sun exposure is really only for a few months a year and we are usually pretty pasty and white by the time the summer comes around again so will burn pretty easily, to begin with anyway.

if anything i think my skin has been more easily burned by the sun since getting ill than before. but that could be down to years being less active.
if i do get full-body sun exposure even for 30mins it now typically makes me feel very tired and lacking all energy. it didn't use to do that.

I don't know the answers but let me just throw this out there for discussion. What if we are viewing this incorrectly? Let's focus on the body as a whole instead of the sum of its parts. Let's say that the VDR doesn't get blocked by pathogens. Why would it down regulate?

We consist of a complex series of chemical reactions that no one understands. We can understand this reaction or that reaction but often fail to understand how one reaction affects or interacts with another. When looking at our microbiome, the bacteria present produce biproducts that our body utilizes. We couldn't live without them. So if we are looking at the VDR and what is happening there, what is going on overall in the body? Increase reactive oxygen species and free radicals are produced by our reactions. Our body is designed to handle these free radicals. If we get a toxin producing pathogen like Borrelia that can alter the pH of the intestinal lining, that can affect bacterial growth. It allows some strains to flourish and others to diminish. This alters the percentage of purines and pyrimidines produced in our GI tract. What this does is alter the nucleosides available for mRNA transcription. If we have more purines produced, there will be more adenine and guanine produced. If we have more pyrimidines, then that will mean more thymine, uracil, and cytosine.

Factored into this is the availability of important vitamins like niacin, thiamine, etc. You won't make niacin without purines so these nucleosides must be "shared" to make what we require. This matters because the homozygous epigenetic shift for VDR Taq is AA or two adenines. For that shift to occur, there needs to be excess adenine available. Pyrimidines availability directly influence our innate immune system as well. What bacteria make excess adenine?...........Gram negative. We know that higher percentages of gram negative bacteria in our GI tract increase inflammation. There are studies (I have them somewhere) that show the breakdown of production of each nucleoside with each phylum of bacteria. I just referenced the easy parts, it is much more complex and no one understands it all.

Long story short, all our body wants is lower oxidative stress. If it can't lower the oxidative stress through normal means, it will resort to flipping genes on and off. If you don't kill certain pathogens, you don't have to deal with the oxidative stress that occurs when they die and you have to remove that toxic debris. It's not just the bacteria in the GI tract, they are all over the body for us Lymmies. The integrity of our tight junctions has long since been compromised and we're fighting on all fronts. Just a different angle.