Vitamin D

I just found out that my Vitamin D is low! I thought that sarc patients had high Vitamin D. Mine is 20 and they said normal is 25 to 65, I think. Is anyone else here low in Vitamin D?

Michele

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Patients with sarcoidosis (and other granulomatous diseases) have an increased risk of getting a high vitamin D but it is not in all cases. Only 50% of sarcoidosis patients have been reported to get high calcium in the urine (one of the earlier symptoms of high vitamin D). This is why it is suggested that people check levels (1OH and 1,25 OH as well as ionized calcium and PTH) before either supplementing or restricting vitamin D. In some cases it is not only a good idea to take extra, it may be needed.

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My last level was 8.6, the lowest it has ever been. I am starting back taking high doses of vit D suppliments. It has been a constant battle over the past year. I am sure it is part of the disease even though most sarc patients have a high level.

Jennifer

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My last D levels was 13.1. When the D levels go low my PTH (Parathyroid) goes thru the roof. I was prescribed 50,000 units of D for 2 weeks. Did not get it filled. If I truly have Sarcoid I will not take this. Right now I am on Citracal with D. (2 a night) This has brought up the D levels in the past but I slacked off. I am sticking with this now.

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Hi Michele and Tex Rose

PTH is key to assessing vitamin D levels in sarcoid. If PTH is low along with low D, vitamin D supplementation is contraindicated. PTH stimulates 1,25 D production in the kidneys.

There is great confusion out there in the clinical world regarding vitamin D. What applies to the majority of people regarding vitamin D, does not apply to people with sarcoidosis. They are finding out more and more about the role of vitamin D in sarcoidosis with each passing day and doctors cannot possibly keep up.

Firstly, there are two D metabolites measured by labs. If a doctor merely asks for a vitamin D level they measure what is called 25-OH vitamin D3 or 25D. This molecule, despite what the nutritionists and doctors tell you, has absolutely no role in the body whatsoever except as a precursor to the active metabolite which is not a vitamin, but a steroid hormone 1,25D.
In people without sarcoidosis this 25-0H vitamin D 3 is produced by going out into the sun where ultraviolet B rays fall on keratinocytes in the skin. This induces a substance called 7-dehyroxy cholesterol. 7 dehydoxy cholestrol forms pro vitamin D then pre-vitamin D which then passes to the liver where due to the action of enzymes in certain cells it is hydroxylated (the OH in 25-0H D) into 25D. This has the potential to become active vitamin D (1,25D) but it isn't active vitamin D until another step. It has to pass to the kidneys where due to enzyme action it is hydoxylated into 1,25 D.

It is actually normal for a person with untreated sarcoidosis to have a low vitamin D (25D). In actual fact, if a doctor tests you for vitamin D it is 25D that he is testing. It is normal for this vitamin D to be low because it is low as a result of the disease process. I will get onto why this happens in a minute. Correspondingly, if doctors measure the 1,25D in a patient with untreated sarcoidosis, it will usually be high.
This actually means the person has a high (1,25) rather than a low vitamin D because the substance doctors measure in a blood (25D) test only has the potential to become vitamin D. Thus the vitamin D levels in untreated sarcoid are usually 25D low and 1,25D high. Doctors misinterpret this because they don't realise there is more than one vitamin metabolite or that these change in a disease state like sarcoidosis.
Unless a doctor specifically asks for 1 alpha hydroxy vitamin D 3, or 1,25D he is only asking for something that has the potential to be vitamin D.

Now I mentioned vitamin D (1,25 D) is a hormone. All hormones work on a feedback system. If there is not enough of a hormone, a signal is sent out to make more. If there is too much, another signal is sent out to stop production. This produces a balanced state.

In a healthy individual when 1,25 D binds to the vitamin D receptor it allows the gene transcription of an enzyme called CYP24 which has the ability to break down excess 1,25 D.

This does not happen in sarcoidosis because the Vitamin D Receptor is blocked, often by 25D, which acts in much the same as prednisone dampening immunity and inflammation. This is good up to a point but like prednisone 25D ends up having side effects because it is converted into 1,25 which in excess causes symptoms similar to those of steroids like weight gain, fluid retention, headaches, nausea and anorexia, neuropathies - all symptoms people with sarcoid experience.

With 25D blocking the VDR it cannot work properly to transcribe the genes which perform other body functions like making enzymes, antibacterial peptides or regulation of the hormone system generally. This is why people with sarcoid often have difficulty with menstrual periods or have thyroid problems.

Another reason why 25D is low in people with sarcoid is because instead of 1,25D binding to the vitamin D receptor, it binds to the PXR receptor just down the road. In effect, in sarcoid the 1,25 D binds where the 25D should bind and vice versa. When the PXR is activated by 1,25D it causes an enzyme called CYP27A1 to be produced. This stops the production of 25D from pre D3 in the liver. Another reason 25D is low is because a further enzyme activated under the influence of Protein Kinase A (PKA) produced by the granulomas of sarcoid called enzyme CYP27B1 actually speeds up the conversion rate of 25D into 1,25D. This means that any available 25D is converted rapidly into 1,25 D.

If your doctor gives you supplemental vitamin D, not only does it block the VDR and stop production of gene transcription for possibly thousands of bodily functions, because of the PKA produced in the granulomatous inflammation of sarcoid any vitamin D given to you supplementally will be rapidly turned into 1,25 D under enzymatic action. However, because the VDR is blocked the enzyme which breaks down excess 1,25 D cannot be transcribed. Thus, the person with sarcoidosis has an excess of 1,25D in their system. This is one reason why some people with sarcoidosis go on to develop problems with their calcium metabolism. When 1,25D reaches a certain level in the blood, osteoclasts in the bone are stimulated to release calcium. The intestines are also stimulated to absorb calcium. This means there can be a build up of calcium levels in both the urine and the blood. However, in sarcoidosis PTH has little effect. Often the PTH is low while the urine calcium is high. More rarely, the serum calcium level is also high. When calcium is high, you often end up with bone loss causing osteoporosis and osteopenia. You also get calcium being deposited in organs, especially the kidneys where they can cause kidney stones or block the tubules causing kidney failure. C alcium can also deposit in the brain, blood vessels and other places, even under the skin. That is a worse case scenario, which is easily treated in any case. Three drugs can help prevent this excessive calcium buildup by blocking the enzyme actions. They are prednisone, hydroxychloroquine and ketoconazole. This is why people on prednisone or hydroxychloroquine will have normal or low 1,25 D levels. Bisphosphonates are sometimes given to postmenopausal women but they are useless if given with supplemental vitamin D. They are not recommended for premenopausal women in any case. Giving vitamin D or cod liver oil to an untreated person with sarcoidosis can bring a person to a hypercalcaemic state within a few weeks. As there are few symptoms until hypercalcemia is well advanced, blood testing is the only way to keep a tab on things.
If you have a low vitamin D and a correponding low parathyroid hormone, you do NOT need to take vitamin D. In a normal person if the vitamin D were truly low, the PTH would increase the hydroxylation of 1,25D in the kidneys. In a person with sarcoidosis (and this is key) the PTH remains low because even though the 25D is low, the 1, 25D is high. In true vitamin D deficiency the PTH would never be low.
So ask your doc for a PTH, if it is high, supplemental vitamin D is indicated, if it is low, steer well clear of supplemental vitamin D because it will actually make the sarcoidosis worse by adding to the extrarenal vitamin D produced by granulomatous inflammation. This excess 1,25 is not broken down because of the 25D blocking the very receptor 1,25 D is supposed to bind to.

Pris

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Pris, that was a great explaination. Thank you.
Would the amount of Vit D produced by sun exposure be enough to cause a negative effect?

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Thanks everyone for responding.

Paradox,

Thanks - I was hoping you'd respond. I'll talk with my doctor about getting the other levels checked (1OH and 1,25 OH as well as ionized calcium and PTH)

Pris,

Wow, that was a lot to absorb (pun intended). I think you were saying the same thing as Paradox (get the other levels checked to see if I really need supplementation)? Thanks.

Michele

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paradox,
my calcium runs around 9.4 to 9.8 mg/dl,i have high calcium along with high creatinine of around 2.5 to 3.0. I get my blood work done every 2-3 weeks,to keep a eye on it. The doctor also keeps a close watch on bun,glucose random,sed rate.Thats how we control the kidneys. Along with sarcoids,I have renal faliure.That's why we keep lookinat the labs. Since i have you on line .Have you every heard of microvas. It's a form of electric inpulses,to control,(so they say) pain in feet,along with other pain areas.
Keep in touch, IO like your comments
Larry

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Pris,
My calcium is considered to be normal,9.4 mg/dl. My creatinine is 2.9 which they determing is high. The doctors asked if i was takind vit d suppliments. I told them no. They could not understand why it was so high.Found out i was in the sun to long. Could this be true?. They now calculate it a different way which comes out to be 12-13 on some scale. So they say things are ok. I would be interested in your oppion.
Larry

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Thanks to J. S. Adams, vitamin D researcher par excellence, yet again, I found a study that showed that patients on prednisone, supplemented with calcium had limited difference made to their vitamin D levels. In certain types of lung disease, probably including sarcoidosis as Adams has done a lot of work on vitamin D and sarcoid, Adams et. al. found supplemental calcium actually lowered serum calciferol (25-OH D) even further. If 1,25 D is high and 25 D is low, calcium is of no benefit because 1,25D is already stimulating absorption of calcium through the gut as well as resorption of calcium from bone. If you have a high 1,25D level, taking calcium, slows production of 25 D in the liver. This seems to puzzle some physicians who are likely to want to put their patients on even more vitamin D which continues to fuel the disease state.
I would be happy to provide a reference if necessary.
Pris

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Hi Larry,

I am not a physician and therefore decline to comment on the limited amount of information you have provided. You don't give the units in which the calcium is measured. As a qualified lab tech, in my own country, I am allowed to advise doctors on what further tests they might do after patient test results are in.

Vitamin D levels in a sarcoidosis patients vary with the seasons and the geography, i.e. where a person lives relative to the equator. Thus a person in northern Canada is more likely to need supplemental vitamin D than a person in south eastern Australia or the USA. However, it also does depend on the amount of time you spend in the sun and how much of your skin is exposed.

There have been patients with normal serum calcium levels who have had a loss of kidney function due to hypercalciuria. More tests of kidney function and urine calcium would clarify the situation.

It also depends on whether or not the sarcoidosis is treated. Such problems are unlikely if a patient is taking prednisone or chloroquines.

Greater muscle usage than normal can elevate creatinine, as can sarcoid in the muscle. This is nothing to worry about.

Stay out of the sun if you live in the south eastern States, especially during the summer. This will help lower your D levels.

If you are concerned, a urine calcium level would clarify things.

If your doctor doesn't think such tests are applicable always ask for a reason.

If there is still cause for concern, do some research on your own. Start swotting up on this stuff, print out a few articles to show doctors if necessary, preferably medical journal or medical text book articles. I have had mixed reponses when I have done this. Some docs have refused to look at them, others have looked at them and thanked me for providing them. Ultimately, it is your body and the more you are informed about sarcoidosis, the more informed decisions you can make about your doctors' opinions. Sometimes doctors are right and sometimes they are wrong. This can sometimes depend on the information they are given by the patient.
I suggest you look at Mary Shomon's web site, she is a patient advocate who writes on autoimmune illness and recommends self-education by patients about their condition. By all means keep a record of your results because this can help you in consultations with doctors. I had a flare of sarcoid in 2006. My own doctor didn't think it was, even though I had been through it all before (twice). I saw two other doctors on the way to a diagnosis. If you don't think a doctor is right about you, get your facts straight and if they decline to help, find someone who will.

Mary Shomon's book can be found here:
http://books.google.com.au/books?id=pLXqHAAACAAJ&dq=Mary+Shomon&ei=edVZSLCi NIO6tgOi6IS_DQ

She is a patient advocate and writer
http://www.cfsfibromyalgia.com/contact.htm
And can be contacted by anyone. She does believe you should educate yourself about all aspects of your condition.

Pris

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Hi Mary,

The attitude of the medical profession is that if you don't have enough 25 D stores you cannot have enough 1,25D either. This simply is not the case in untreated sarcoidosis when 1.25D levels are often high. My 25 D was 7.6 in US conventional units or 42 (ref 51-140 nmol/L) but is even lower now, give me a minute and I'll work it out--- yeah it is now 5.6. According to the lab and Australian standards I have a mild deficiency. I don't yet know what my latest 1,25D is. I hope I will found out on the 24th. If I really had a vitamin D deficiency my PTH would be sky high trying to stimulate the kidneys to convert more 25D into 1,25D. This test was ordered by my specialist and he told me he wanted my 25D up around 65. He suggested I supplement with vitamin D. I have decided not to take it. I requested a urine Calcium. It came back on the high side of normal, 6.3 mmol/day (upper limit 7.5.) I believe this is too close for comfort. My corrected serum calcium was within reference range but a definite upward trend is emerging there since I stopped Plaquenil. My serum phosphate is out of range (high) indicating bone resorption and corresponds to the rising trend in the calcium. My PTH is clearly normal at 4.3, upper limit 7.6 pmol/L. I asked my primary care physician to do these tests and she agreed. The decision we came to based on subsequent results is that vitamin supplementation is contraindicated especially while my ACE is rising, and no longer on drugs which are antagonistic to 1,25 D i.e. prednisone and plaquenil. Bone scan indicated a 7.2 % loss from spine and 6.7 % loss from femur since last scan indicating bone resorption and I am now officially osteopenic. I have just found a study that indicates supplementation while on prednisone does not prevent osteopenia developing. See
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2265.1982.tb00734.x
I will continue to learn all I can about vitamin and bone mineralisation in sarcoidosis because I know I am going to have to give a reason to my specialist as why I am refusing to take vitamin D upon his recommendation. It might as well be a well researched reason and while I am in the process, I can alert others to the dangers and misconceptions regarding vitamin D in sarcoid. For instance, did you know that 1,25 D binding to the vitamin D receptor is responsible for transcription of 913 genes and may be responsible for transcription of up to 29,000 genes.
Oh, and whats more, my biochem text book from back in 1984 (Kaplan and Pesce) mentions extra renal production of 1,25 D in sarcoidosis. So docs have had more than twenty eight years to get up to steam on vitamin D metabolism in sarcoidosis. There's no excuse.

Pris

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Hey Pris--
Thanks for the update on the metabolites and Vitamin D. My cardiologist put me on 50,000 IU Vit D and I did feel worse, and plus, my numbers did not go up. I am not a scientist, but now I'm worried about taking the supplements. I have been off prednisone for a couple of months now, so I guess I'm untreated sarc. I don't think she will listen to me unless I have a source for all this info you are posting. Do you mind sourcing your info for my doctor? I don't want my sarc to get worse. Why haven't I heard any of this before? It boggles the mind.

Maybe you could help with what I should say to my doctor -- thanks so much.
Marcy

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Pris,
Thanks for the information.
Larry

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Playing catch-up between some long shifts, please bear with me.

In general, it really isn't possible to accurately describe any of these lab values alone. To do so is to simply look at numbers and not the whole system. As a great example listed above -

Pris, I would say your PTH is elevated and not normal since you have elevated calcium and phosphate. Remember, there is "lab normal" and "patient normal" and the two may not be alike - much like a "normal" retic count in a patient with profound anemia. If I were to just look at PTH alone, I wouldn't know it was much higher than it should be in this case. Although following the labs is a way to try and follow a disease course, physicians and patients should understand what they are looking for (I hate when docs order labs that they don't really know how to interpret or that won't give any guidance).

So, what is needed to really interpret these labs? At the most basic level a Calcium measurement - serum or ionized, although serum calcium levels really should have albumin included; also a PTH, Phosphorous in at least some conditions, Vit D at least 1,25-OH and 25-OH. There are also times when a serum chloride and possibly a serum bicarb could be useful, but this is less likely in the population reading this board. I would not assume that a low PTH and 25-OH vit D mean a high 1,25-OH Vit D... measure that too because they could all be low, especially for people on medications like prednisone, plaquenil, chlorquine and a few others.

Larry - a creatnine of 2.9 is something I would want to follow as a physician. That is indicative of some kidney damage. Even if you are built like Govenor Arnold and just had a massive week of working out and muscle break down that number should not be that high. That is a high enough level that it is strongly indicative of at least chronic renal insufficiency which can be caused by...
Hypercalciuria..... among many other things. (Calcium doesn't just block the renal tubules, in high doses it is toxic to them.) I'd be following those other levels as well, but more importantly I'd be following electrolytes. Remember, the only efficient exit route for most ions in the blood is through the kidney, so you want to make sure things like potassium, calcium, phosphorous, etc... don't get backed up.

Also, I still strongly suggest you don't start restricting sunlight, dietary vit D or calcium unless you have excess - remember, you can't manage these levels if you don't measure them (throw that line at the doc). By the same token, don't supplement without finding out that you are deficient.

Marcy - you can have your doc do a lit review for it. Here's a good article for him to start with that isn't too old:

Sharma, OP. Vitamin D, calcium and sarcoidosis. Chest 1996; 109:535

or

Inui, N., Murayama, A. Sasaki, S, et al. Correlation between 24-hydroxyvitamin D3 1 alpha-hydroxylase gene expression in alveolar macrophages and the activity of sarcoidosis. Am J Med 2001; 110:687

these are the latest articles I found worth mentioning on the topic (at least dealing with sarc specifically - as Adams and the others did research on many types of granulomatous diseases - can't always assume what is true in one applies to another). If you want to give your doc a real heads up and make his life easy though...

Hypercalcemia in graulomatous diseases

That's the title of a summary article on the physicians resource called UP TO DATE - have him look it up - covers all this and more.

Hope that provides at least some assistance... need some sleep now before my next shift.

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Hi Mamayama,

O Sharma's journal article is excellent and is available on the web. You should be able to print an abstract off to show your doc.

Other good articles or chapters are

Chuson, Kelly D. & Tilley, Stephen L. "Sarcoidosis" ch 29 (271–276) in Ringe, Marschall Stevens, Principles of Molecular Medicine.

Ringe, Johnann D, Osteoporosis in Dialogue (100 Questions) see page 85. for sarcoidosis.

Excellent and recommended chapter:

Adams, J.S., "Extrarenal Production of 1,25-Dihydroxyvitamin D and its Clinical Applications", (337–356) in Holick, Michael F. PhD MD, Vitamin D Physiology, Molecular Biology and Clinical Applications.

More controversial is a book
Stolz, Veronica, Vitamin D- New Research.

The main thing to be aware of is, if you have sarcoidosis and are having vitamin D supplementation, you should have regular calcium levels done on urine and blood.

To have them done on blood is not enough because many sarcoid patients who are normocalcemic can already have kidney damage.

Hypercalcemia of sarcoidosis is highly responsive to prednisone or chloroquines. If it doesn't respond within a few days another cause needs to be found.

Don't worry, just be aware. Sharma's article is an excellent starting point. You could raise it with your physician if they are not aware of extrarenal 1,25D in sarcoid. I have been skimming through some texts of Google and many are not up to date regarding the extra renal production of 1,25 D in sarcoidosis.

http://www.ncbi.nlm.nih.gov/pubmed/8620732
An abstract of Sharma's article can be found above.

Also, it might be wise to avoid midday sun in high summer as hypercalcemia in sarcoidosis has been noted to occur from excessive sun exposure alone.

Pris

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Hi Paradox,

You are far more knowledgable than I and obviously have a lot of clinical experience.
You mention my PTH. My last three phosphate levels have been successively higher. Calcium is still in the lab range. You think my PTH is comparatively high? You mention measuring Cl and HCO3. As a matter of fact, the last few tests they have been at the limit of the normal range for each. The last test done, Cl and HCO3 had come it a point. My last test results showed raised BUN, creatinine and uric acid, globulins and eosinophils. ACE was 91. My eGFR was 51 by IDMS formula. My doc said nothing about it and left me for six months follow-up. I was a little shocked when I first rec'd results in the mail as I have never had any sign of kidney problems before. I am over it now, though.
I figure we're all in this sarcoid thing together.

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Hey Pris,
If your serum ca is still normal I wouldn't call the PTH outright high (I was tired and for some reason thought your serum Ca was high as well). A high serum Ca should drop the PTH towards 0 very quickly, so anything in the "normal" range would be abnormal in that setting.
There are times I will look at a serum Cl and HCO3 to help make some determinations. Serum Cl around 103 to 115 (just low or low normal) in the presence of a slightly low HCO3 tends to be a serum buffering pattern that is consistent with high PTH especially in hyperparathyroid states. Serum Cl below 103, especially with a high normal or elevated HCO3 tends to suggest the rare milk-alkalai syndrome.
I have to admit that an eGFR of 51 alone might not get me too excited either, but I would be more concerned since it comes with the rising creatinine and uric acid - the globulins and eos would catch my eye too. Several different processes cross my mind at the mention of all that. Think I'd be wanting good hydration and quicker follow-up tests than 6 months out.

The references I chose, by the way, were selected by date specifically because I know so many docs won't even look at anything more than 5 years old if they can help it. I haven't seen anything as recent by Adams - although he and Sharma did some work together on the in-vitro studies of PAMs a while back if I recall. Still a very solid piece of evidence. He has also been doint research in the other granulomatous diseases, but it is very obvious that sarc and lymphoma get a lot more of the attention than the others.

Stay well

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I don't know if it's just my brain fog, but I'm very confused now. I don't even know where to begin to sort all this out.

Someone help?! Or maybe just laugh...

Michele

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Thanks for all the good advice, Paradox and Pris. I will print out some articles. My doctor says there is not enough evidence either way to support or not support vit. d supplementation, which sounds like a copout response (this coming from leading sarcoid researcher!) What to do? It's really hard having a disease very few people know anything about, (and it can go so many places, it's hard to find an expert in even one area). I'm a little discouraged. I have been feeling better since I started the South Beach Diet, which I recommend for sarcoid, though.

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I'm with Michele5, I'm rather confused. I had no idea calcium/Vit D was an issue with sarcoid. I'm not treated for sarcoid with anything but Advair and an inhaler. I have however been on Vit D supplements for the past 4 years because of having osteopenia diagnosed in a bone density test. The last test showed no osteopenia. I guess I'll talk to my pulmonary doc when I see her later this month. I'm not sure whether I should quit taking the D or keep taking it. What happens to the body if there is to much vit D in the body?

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