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Vitamin D metabolites as clinical markers in autoimmune and chronic disease

Vitamin D metabolites as clinical markers in autoimmune and chronic disease.

Journal: Ann N Y Acad Sci. 2009 Sep;1173:384-90. Authors: Blaney GP, Albert PJ, Proal AD.

Affiliation: Stillpoint Centre, Vancouver, British Columbia, Canada.

This was e-mailed to me through co-cure, an organization that keeps physicians, researchers and patients in on the latest research for (mostly) Chronic Fatigue Syndrome and fibromyalgia.

For a link to this article on vitamin D deficiency and DYSREGULATION... check out:


Reversing Bacteria-induced Vitamin D Receptor Dysfunction Is Key to Autoimmune Disease:


Dysregulation of the vitamin D nuclear receptor may contribute to the higher prevalence of some autoimmune diseases in women:

33 Responses
Avatar universal
I just had my D level checked.  Surprisingly, it was completely normal.  IMO this rules out my  "official" diagnosis of FMS.
237053 tn?1258828426
My Vit D was normal too.  Hmmm???  
Avatar universal

If I remember right... you vitamin D could be within normal range, but you need your vitamin D 1,25 results to do the math:



Avatar universal
As far as my results... my vitamin D 1.25 hydroxy level was 58  pg/ml and was 3.05 sigma high. I was told that based on population studies, 99. 89% of the population would be expected to have a lower number. It is above the Merck Physicians Guide maximum of 45pg/ml.
Avatar universal
My vitamin D ratio was 2.23... a clear sign of Th1 inflammation.
Avatar universal
"IMO this rules out my  "official" diagnosis of FMS."

It wouldn't until you find out what your vitamin D ratio is. Of course this is the latest research just released, but I can tell you that ALL of us pretty much on the MP had vitamin D dysregulation... due to intracellular bacteria. Of course the MP has chronic lyme disease patients on the protocol and they tend to have the same results.
Avatar universal
I'm not sure all that was done.  I just got a call that said my level was 39 and was normal.
Avatar universal

You might want to consider asking your physician if he/she did a vitamin D 1,25 hydroxy level on your blood. If so... check out the MP link and find out what your vitamin D ratio is. It isn't a definite test obviously, but something that points in the direction to intracellular bacteria.... which is apparently is found in two-thirds of CFS and fibro patients.
428506 tn?1296557399
My ratio was >4 at first (by which I mean when I first saw my LLMD).  My 1,25 level was not unusually high, the other was just unusually low (single digit).

Thanks for bringing up an interesting topic with some links, PG.  I honestly don't understand the role of D in Lyme or other chronic illnesses, but am interested in learning more views and ideas on the subject.
Avatar universal
To make things even more difficult most labs are notoriously unreliable for an accurate measurement of especially 1,25D. I know the Marshall Protocol folks recommend using only Quest labs in California. I got an order from my doc, and then printed out the information from Quest, and gave it to the lab tech at the hospital. Most hospital labs use Quest so it's not a big deal for them to send it there. Here's a link to the test if it passes MH's filter: (Otherwise I'll put it in my journal)


I have to agree with Vitamin D dysregulation being the result of chronic disease that is caused by a successive chronic intra-phagocytic infection of multiple species of CWD bacteria. Mainly because I have Sarcoidosis, the same disease Trevor Marshall had when he discovered the cause of the disease. I'm currently on the Protocol, and am herxing on doses of Minocycline that most doctors would consider laughable. But that's because the MP's primary focus, and goal is to restore innate cellular immunity, when that happens it takes very little abx's to induce a herxheimer reaction. If you give a MP patient a standard dose of tetracycline's it could very well be fatal. But this is all new territory, I just hope it is taken serious by mainstream medicine sooner rather than later. Here's some links to discussions about Vitamin D from the Marshall website: Take care ~Corvin


Avatar universal
Hi everyone,

Hope I can tag on to this discussion without adding too much confusion to the mix...

I've been sick for a few years. Diagnosed several months ago with several autoimmune diseases. Finally found a LLMD and requested to have my blood sent to Igenex in CA. (I've tesed positive w/ELISA tests in the past but have been reactive repeatedly only to 41kd IgM with traditional Western Blot). I also requested to have my D1,25 checked and am awaiting both results.

Here's my question: I've had severe Vitamin D (25-Hydroxy) deficiency many times in the last few years and have always been prescribed the big green 50,000IU pills which bring the number up for a couple of weeks and then it drops again...same goes for most of my other vitamins/minerals/iron etc and this has always been attributed to GI malabsorption problems.


I just received labs from 3 years ago. Turns out my 1,25 was checked then and was 51mg/mL. This was considered normal by the lab, but I've read that according to Merck, it is high. My D,25-Hydroxy was 65 on that day, but this was while I was supplementing 50,000IU Vit. D.

1 month before these tests (and before I'd started supplementing), my D,25-Hydroxy was only 15.

I'm familiar with the value of Vit D ratio and the MP. So...the big question...Which D,25 value should I use to figure out my ratio? The value before I started supplementing (15) or after (65)? Or does it even matter if my 1,25 was high in the range?

Thank you in advance!!!

Avatar universal
Hi Leigh, good to talk to you again ! You have to have them both tested at the same time from the same blood draw you can't calculate old results with new ones. I never had to mess with it myself because with biopsy proven Sarcoidosis, and an elevated ACE it was proof enough of a Th1 disease. I had 25D checked once I had already started the protocol (should be checked pre-MP regardless) to make sure it was where it needed to be for therapeutic range, and I'll continue to check my 25D every so often just to make sure it stays below 12 ng/ml. My 25D was less than 4, or basically undetectable from an Aug 7th blood draw, that's while avoiding exogenous D for four months. I tried to get both checked pre-MP, but they pretended to "forget". Most Pulmonologists have heard about the MP, and are actively opposed to it, but I know they don't take the time to actually understand it because they think the antibiotics are supposed to act as anti-inflammatories. LOL :)
Avatar universal
Hey Corvin!

Good to talk to you, too! I've been trying to keep up with you through the grapevine...sorry to hear you've been herxing but I suppose you were "prepared" (if that's the right word). I truly hope the MP is exactly what you need to get better.

Well, the problem now is that the doc who's checking my 1,25 didn't check the 25D with it! But my OH was checked less than 2 weeks ago and was low again (17). I haven't taken any supplemental D since then. I have a feeling that the Lyme stuff will come back positive, and I'll just have to decide how exactly to move forward. I really do think a bacteria is to blame for all of these problems. But with so many nutritional deficiencies and hormonal issues that aren't in good control, especially Addison's, I'm not sure how my body would handle herxing. I'm worried enough about iron infusions, let alone something like the MP! But at the same time, it's hard to say if wrangling the hormones is even possible when there's "something else" going on...

Anyway, thanks for your post. Sending you lots of good vibes and hoping you turn the corner soon...

Take care,
Avatar universal
Thanks Leigh, I'm hoping I can get through the MP in about three years beings I was never on long term steroids, but it may be closer to five years. Ten days or so your 25 probably isn't going to change that much if none of your habits changed, it's just not going to be as reliable as doing it at the same time, and if it's measured by two different labs I wouldn't trust it to calculate. Doing them together, and using Quest Labs, and the protocol for handling the specimens puts an end to all the confusion, and inaccuracy.

Probably the best test for an occult or hard to culture bacterial infection is a therapeutic probe of broad spectrum abx's like tetracyclines to see if they elicit an immunopathy or herx reaction. I don't think there is anything wrong with a standard abx protocol for acute or chronic stage Lyme Disease except I think pulsed moderate dosing with multiple abx's is better, like mino + azithro, or mino + azithro + x  every other day. That joke I made in my last post about abx's acting as anti-inflammatories actually isn't a joke they use high daily doses of azithromycin for palliating rheumatoid arthritis which is good if you want to feel good, but not so good if your trying to elicit an immune reaction to kill a chronic infection.

But if your D ratio is indicative of Th1 disease then a probe of the MP would be better. In a Th1 patient their innate immunity is compromised, and they can test positive to co-infections that the immune system just can't deal with properly, and Bb (borrelia burgdorferi not B flat) is just one of many that can contribute to the chronic disease state.

Any abx treatment you can modify it to your own tolerability. The MP their concern is taking to much abx, and trying to go to quickly so if it's still intolerable after increasing the ARB dose you just back off the abx's, cause like I said before abx's aren't the foundation of the MP. But they have the dosages worked out pretty good I think, biggest thing is don't ramp to the next dosage before your ready. ~Corvin
Avatar universal
my vitamin d was low.  THe dr. did not tell me what it was but now i am on 55k IU every 5 days for 6 weeks.  I have been tested for RA and lupus both were neg.  I have been tested for hyperthyroid  3 times every time it comes back normal.  I can not take cortisone because it turns me bright red and makes me hurt ten times worse than usual.  I have been diagnosed with Raynauds syndrome and neuropathy in legs and feet.  If my vitamin d is low shouldn't I have abnormal calcium levels.  Oh and my resting heart rate is 110bpm but blood pressure is perfect 90over60.  I am tired of hurting and tired of being tired.  
237053 tn?1258828426
I just got my lab results out and this is what it say:

25-OH Vit D TOT...........39         Reference range 20-100
25-OH Vit D3 ...............39
25-Oh VIT D2................<4

Can someone interpret these for me??  

Avatar universal
Hi skarey,

Those are both inactive 25(OH) readings. So your inactive 25(OH)D3 was 39 at the time your blood was drawn, and tested, but they didn't measure your active 1,25(OH)2D3. When they measure 25(OH)D2, and 1,25(OH)2D2 it can help tell them how much D your getting from diet or supplements because vertebrates don't naturally produce D2. It's more of a matter of the source, but the end result is the same. D3 is made endogenously in humans skin by 7-dehydrocholesterol, and UVB radiation, D2 is not.

Just to clarify (OH) is the chemical acronym for an oxygen, and hydrogen bond, or another words a hydroxy. (OH) represents a single hydroxy, and (OH)2 represents two hydroxyls in a chemical compound. The extra hydroxylation in Carbon 1 is what makes Vitamin D bond to the Vitamin D receptor, and activate it. Saying 25(OH)D3 is just a shorter way of saying 25-hydroxycholecalciferol, and 1,25(OH)2D3 is a shorter way of saying 1-alpha,25-dihydroxycholecalciferol.

In US measurements 25(OH) is measured in nanograms(ng)/milliliter(ml), and 1,25(OH)2 is measured in picograms(pg)/milliliter(ml).

Hi Heather,

I know even the mainstream says when your 1,25D gets pretty high it can lead to hypercalcemia, but according to Dr. Marshall, starting when 1,25D is around >43 pg/ml it can start to remove calcium from the bones, and deposit it in soft tissue even though the serum level of calcium may be normal. That's reason enough right there to have your 1,25D checked along with 25D. Osteopenia is a common sub diagnoses in Th1 patients, and low calcium, magnesium, and phosphorus intake can still obviously be a contributing factor. But giving any type of Vit D to a Th1 patient can actually contribute to developing osteoporosis, not prevent it. The only sure thing I can say is I have Th1 disease, and my calcium is normal, although I may need to supplement individually because most dairy products are fortified with D, and I can't tolerate exogenous Vitamin D.
Avatar universal
Hey Corvin,

Hmm...so I just found out I have osteopenia. Thought it was from long-term high-dose steroids and/or high Calcium and Phosphorus from Addison's...but maybe it was from the high D1,25 I didn't know I had?? I think the hypercalcemia is what gave me pancreatitis.

Just had a lip biopsy for possible Sjogren's (one side of my face is puffy and the rheumy thought it was from salivary gland swelling). The path report just says "nonspecific" inflammation of the salivary glands, not necessarily indicative of Sjogren's. The rheumy asked me if I'd ever been checked for Sarcoid, and ran another ACE level but it came back the same as before...45. What do you think?


Avatar universal
Hi Leigh, yeah a high 1,25D can start to dysregulate the glucocorticoid, thyroid, parathyroid, thyroid, estrogen, and androgen receptors also, and it's worse in women, except androgen obviously. I know the MP says if your on thyroid hormone, that you have to really watch the level in the first few weeks of the Protocol because when the 1,25D drops the TSH will shot way up again, and replacement isn't needed anymore. The adrenals, and parathyroid I'm not sure, they take more time to stabilize I think, you can also search it more on their website. The VDR also controls >913 genes, and the calcium channel is one of them.

Jes 45 that sounds a little high to me. Depends on your labs reference range, my labs cut off was 46, and my result was 56. So mine wasn't really super high or anything either. The average healthy person's ACE is more in the teens, so if your in the forties that seems a little suspicious to me. But steroids mess up the reliability of results quite a bit too. I don't remember if it makes it higher or lower though. I know ARB's make it higher.

P-gal or someone with Sjogrens could tell you more about diagnosing Sjogrens. All I can say is an inconclusive lip biopsy wouldn't rule out Sarcoidosis. Where you almost always find multinucleated giant cell granuloma in Sarcoidosis is interstitial lung tissue. I've heard also that needle biopsies aren't very reliable in diagnosing Sarcoid because the granuloma can get destroyed in the process, and the fact that the sample size is so small, kind of simular to diagnosing lymphoma, the bigger, and undisturbed the sample size the better.

I think it will be interesting to see what your 1,25 is, I would still go to the marshall site, and calculate it with your 25 you had a few weeks ago if the same lab did them both. If the ratio is okay then I would get it done again the same time through Quest. I think the biggest thing is that the 1,25 sample is frozen, if it's in the fridge more than 3hrs it isn't reliable, you don't have to have Quest do it, but Quest will reject a sample that isn't frozen, and they can separate out the D2, and D3 better than most labs.
Avatar universal
Hey Corvin,

Thanks (as always) for the good info. So - I was just going over some labs the hematologist ran last week, and my CD4/CD8 ratio is high (4:1). I read that this, combined with a high ACE level, is suggestive of Sarcoidosis. Is this true?

The lab cut-off for the ACE was 67. I've had it checked twice before, and it's 45 each time (even before I was on steroids). Hmm.
Avatar universal
p.s. The reactive band on my Lyme WB tests is the 41kd IgM, which I read can be reactive in any spirochete L-form bacteria, not just Lyme...
Avatar universal
Correction on my last post, I meant T3, and T4, not TSH.

I went back, and looked at my test reports from last April, and Mayo did a T and B cell quantitation, from my bronch washings(BAL), and this is what it says:

%CD3 (T Cells) 95%
%CD4 (Helper Cells) 81%
%CD8 (Suppressor Cells) 22%
%CD19 (B Cells) 0.00%
%CD16+CD56 (NK Cells) 5%

But then in the notes it just says "no established reference value", and that's it. So I'm not sure what it all means. I guess 81% would be about four times the value of 22%, so my ratio would be 4:1 also. But that's just my own speculation, from looking at the results, maybe that's not how you figure the ratio. My Lymphocyte% in relation to WBC will be low sometimes too, but then you can check it a month later, and then they'll be in range again. I remember Marshall talking about CD4/CD8 before, but my memory is pretty worthless anymore, I'll have to go back, and try and find it again.
Avatar universal
Hey Corvin,

Thanks for the info. I knew what you meant with the thyroid! :) Yes, I think that's how they figure out the ratio. So ours is the same. According to my hematologist, anything above 2.5:1 or so is unusual. I always used to have low Lymphs too. Right now they're low again. With steroids, my neutrophils have come up (used to be low) and eosinophilis have come down (used to be very high). Inflammatory markers are normal now, too, but my whole body is inflamed, it seems! As soon as I get below a certain amount of steroid, my rashes get bad again, GI stuff, aches and pains, that kind of thing. More than anything I feel sort of "allergic" in a weird way. My total IgE is high, so technically I am reacting to something, but so far nothing typical has turned up on allergy testing...

I'm still taking a little more than a "physiologic/replacement" dose for the Addison's, trying to taper down to something more reasonable. Just found out I have osteoporosis and degenerative arthritis (presumably from steroid over-treatment) at the ripe old age of 29. Gotta love it.

I've never had a bronchial washing b/c to date, I've never really had any lung symptoms. So my CD4:CD8 is plasma.

Sarc sure would explain a lot of what's happened. Don't know if it would be the cause of the problems or just another one to add to the group...there is definitely a genetic tendency in my family for the autoimmune endocrine stuff, and I've had some weird genetic tests (mutations) come back positive recently...who knows. I've read that Sarc runs in families, too...

As far as possible symptoms would go, these are the things I think might qualify for Sarc - would love to know what you think.

-"a few hypodense lesions" on my spleen 2.5 years ago (CT scan), "too small to characterize but may represent cysts or granulomas".
-MRCP 1 year ago showed "an area of poor enhancement in the liver, possible hemangiomata".
-same MRCP showed "probable C-section scar" in uterus (I've never been prego or had a C-section).
-diagnostic laparoscopy 1 year ago found most of the colon adhered to the pelvic sidewall on both sides. No endometriosis, just adhesions.
-recent lip biopsy showed "foci of moderate chronic inflammation" in salivary gland. It's healed and is now a very hard fibrous lump.
-recent colonoscopy showed "scarring and fibrosis" in sigmoid colon (all of my EGDs/colos show "chronic inflammation" everywhere.
-Addison's, hypothyroidism, premature menopause, pancreatitis, rashes, eye pain and vision changes, atrophic gastritis, lots of GI stuff, joint/bone pain, feeling yucky...etc
-Recent 40 point drop in PTH (used to be low/normal, then went high and stayed there, just fell to the bottom of the normal range - all this time D-OH has been low or low-normal)
-Ca has started climbing recently although I don't supplement at all anymore and don't eat dairy. Now it's at the top of the normal range. It used to be high w/Addison's crisis and/or preceeding Pancreatitis, but otherwise was always low.
-some other stuff I can't remember right now...

Thanks again. Hope you're doing o.k. today.

Avatar universal
it is heather again.  I thought it might be lyme disease, because I do find ticks on me frequently through the summer.   Last summer I pulled a tick off my head, didn't think anything about it until my lymphnodes in my neck swelled up.  I kept a sore on my head for three months and my lymphnodes stayed swollen for about the same.  I went to the dr, and since i live in georgia they just treated my with doxycycline. they say lyme disease is not down here.  That was a week after lymphnodes swelled.  I do remember this happening when I was 17, now 33, I ran a fever every night for a month. The dr.'s could not find anything wrong with me.  For over ten yrs now I have been to several dr's just trying to find out what is wrong.  I have every symptom for hyperthyroid but the TSH test is normal (1.03).  The dr even said my thyroid was enlarged.  I have lost all of my teeth, 21and 24 yrs old.  They just brushed away.  I have had countless abnormal EKG's but they do the chest x-ray and say everything is fine.  I am concerned because I have always been dizzy and the dr's said it was caffeine.  That is understandable.  But now my son is dizzy and passing out and I do not allow my kids to drink caffeine.  His pediatrician said it was normal when they started puberty.  I am worried though whatever is wrong with me I might have given to him.  My youngest son was born with PAC's premature atrial contractions and a heart murmur.  The most I have ever weighed was 125lbs when I was nine months pregnant with my first son.  I am completely lost.  Was really hoping that the vitamin D would fix everything.  Still HOPING,  I do not want to go through my thirties like I did my twenties.  honest to goodness I do not even go out in public anymore because i look like a heroin addict.  I have sores on my skin and last time I weighed myself I was 103lbs.  Ijust keep losing weight.  I have been accussed of drugs anorexia bulimia.   I even convinced myself of being anorexic even though I know I need to gain weight, I have never even looked at myself as being fat.  My legs look like a war zone with the scars I have left from scratching.  If anyone knows what I need to ask the dr to test for please let me know.
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