Cytokine Storm & Vitamin D relationship?

[cartski]

Re: Cytokine Storm & Vitamin D relationship?

For adults, the 5-?g (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers, osteoarthritis progression, multiple sclerosis, and hypertension. Total-body sun exposure easily provides the equivalent of 250 ?g (10000 IU) vitamin D/d, suggesting that this is a physiologic limit. Sailors in US submarines are deprived of environmentally acquired vitamin D equivalent to 20?50 ?g (800?2000 IU)/d. The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response that is surprisingly flat up to 250 ?g (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 ?g (4000 IU)/d is required. Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 ?g (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of >=1000 ?g (40000 IU)/d. Because vitamin D is potentially toxic, intake of >25 ?g (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 ?g (2000 IU)/d is too low by at least 5-fold.....
http://www.ajcn.org/cgi/content/full/69/5/842

But what processes are involved to empty the tank?

In other words, what depletes the reserve of vit D faster than the normal half-life rate?

Latitidue explains the slow increase in levels, or the chronic deficiency. But for the equatorial places, that doesn't work. Smog may be an answer, but is there another reason? Could a medical treatment, drugs or another intervention, cause a chronic or rapid depletion despite the high sunlight exposure? Could an illicit drug do the same?

J.

[mixin]

Re: Cytokine Storm &amp; Vitamin D relationship?

Could an illicit drug do the same? J.

Does cocaine usage show up in influenza testing?

[Shannon Bennett]

Re: Cytokine Storm &amp; Vitamin D relationship?

On-line sources for vitamin D.

Vitamin D3

http://www.abcvitaminslife.com/Main/Catalog.aspx?pattern=vitamin+d

http://www.puritan.com/d-vitamins-534?afid=28&safid=nav

I am having trouble finding good sources of Vitamin D2 which contain more than 400iu. But, I did find one Canadian source.

http://www.foryourhealth.co.uk/store.asp?pid=132&catID=10

Here is one containing 800 iu.

http://store.nexternal.com/shared/StoreFront/default.asp?CS=vegane&StoreType=BtoC&Count1=955883204&Count2=873023629&ProductID=2382&Target=products.asp

This site offers several choices. One of the manufacturers does make a tablet which contains 2,000 IU of vitamin D2.

http://www.nextag.com/vitamin-d2/search-html

[tropicalgirl]

Re: Cytokine Storm &amp; Vitamin D relationship?

Living in a South American big city, as for those who lives in NY, Mexico or Buenos Aires I can tell great part of people lives and/or work inside buildings, or inside cars which means that you rarely got a chance to have sunlight, unless you go to roof which is unusual for most people.

When I lived in an apartment I very rarely would have opportunity to be exposed to sunlight, even walking in the streets because the buildings projects shadows so you would be on sun just in a few hours (11am - 13 or 14 am), not a good time to be exposed anyways. As I live in a house now , even being in downtown, I do have a terrace where I can have some sun in mornings or afternoon, including winter... but I do know that it's not an option to most people in here, if you go out early in morning and go back at night, you would have to get sun during your work shift - not an option for many. So I would guess, the smog thing plus the shadows provided by buildings = lack of sunny areas, this could really be a issue. Maybe a idea is to compare how's going the rate of D vitamin and Flu on those cities (like Rio de Janeiro) where people do love to be exposed to sun compared to others cities without these exposure culture... to be discovered...

[prepdeb]

Re: Cytokine Storm &amp; Vitamin D relationship?

I just received a catalog from Swanson Vitamins a few days ago.
I've not ordered from them in the past, but may place an order soon.
They have a promotion going through 8/31/09

The promo code stated on the back of the catalog is MKFP.

Vitamin D3 is one of the 2-for-1 items listed.
250 caps of 1,000 IU Vitamin D-3 - with promo, it's 2 bottles for $5.99 with a limit of 3 plus 3.

Just checked the website - http://www.swansonvitamins.com/
Shipping is $4.99 and there's a spot to enter the promo code in the upper right hand corner of the front page.

[cartski]

Re: Cytokine Storm &amp; Vitamin D relationship?

This NEJM article is excellent info:

http://content.nejm.org/cgi/content/full/NEJMoa0904252

Look at the people - all likely spent most, if not all, of their days indoors:

Among the 14 patients whose occupation was recorded, 6 were students, 2 were taxi drivers, 3 were housekeepers, 1 was a locksmith, 1 was an employee of a billiards parlor, and 1 was a physician who did not have clinical duties and was not an INER employee.

And the antibiotics - are we sure there's no relationship to severity?

Twelve patients sought medical care at other institutions as outpatients before hospitalization at INER and were treated with one or more antibiotics: ceftriaxone (five patients), amikacin (three), azithromycin (one), amoxicillin?clavulanate (two) or other macrolides (three), or another agent (two). Except for two patients transferred from other health centers, the reported hospitalization was the first hospitalization related to the disease.

After admission, 17 patients received ceftriaxone and 10 received clarithromycin. Additional antibiotics were prescribed in several patients, on the basis of their clinical course: three were given levofloxacin; seven, vancomycin; five, cefepime; five, imipenem; and two, dicloxacillin.

J.

[AlaskaDenise]

Re: Cytokine Storm &amp; Vitamin D relationship?

But what processes are involved to empty the tank?

In other words, what depletes the reserve of vit D faster than the normal half-life rate?

Latitidue explains the slow increase in levels, or the chronic deficiency. But for the equatorial places, that doesn't work. Smog may be an answer, but is there another reason? Could a medical treatment, drugs or another intervention, cause a chronic or rapid depletion despite the high sunlight exposure? Could an illicit drug do the same?

J.

(snipped from Merck)

Rarely, hereditary disorders cause impaired metabolism of vitamin D (dependency).

Vitamin D deficiency is a common cause of rickets and osteomalacia, but these disorders may also result from other conditions, such as various renal tubular disorders, familial hypophosphatemic (vitamin D–resistant) rickets (see Renal Transport Abnormalities: Hypophosphatemic Rickets), chronic metabolic acidosis, hypoparathyroidism (which reduces vitamin D absorption), inadequate dietary Ca, and disorders or drugs that impair the mineralization of bone matrix.

http://www.merck.com/mmpe/sec01/ch004/ch004k.html#sec01-ch004-ch004k-BABBBEAE

[AlaskaDenise]

Re: Cytokine Storm &amp; Vitamin D relationship?

Now that I know that Vitamin D is a hormone and that aromatase inhibitors interact with hormones, I found this speculative, but important relationship...
-------------------------------------------------

Vitamin D intake may be a predictor of response to aromatase inhibitors in postmenopausal women with hormone receptor positive breast cancer
Omer Dizdar1, Nilufer Bulut1 and Kadri Altundag1

(1) Department of Medical Oncology, Hacettepe University Institute of Oncology, Sihhiye, Ankara, 06100, Turkey


Kadri Altundag
Email: altundag66@yahoo.com

Received: 1 June 2007 Accepted: 7 June 2007 Published online: 11 July 2007


--------------------------------------------------------------------------------

Without Abstract

--------------------------------------------------------------------------------

To the Editor,

The importance of estrogen in the development and progression of breast cancer has been recognized for some time. Main estrogen biosynthesis in postmenopausal women is catalyzed by P450 aromatase, encoded by the CYP19 gene. Aromatase inhibitors (AI) were designed to inhibit estrogen synthesis in the postmenopausal women. Based on the results of large trials with AI in advanced, adjuvant, and neoadjuvant settings, third generation AI are widely accepted as a part of treatment for postmenopausal women with hormone-receptor positive breast cancer [1]. There are no standard biologic predictors of response to AI. Vitamin D intake is a part of treatment of postmenopausal osteoporosis. In addition, AI itself leads to osteoporosis by decreasing circulating estrogen levels in postmenopausal women necessitating osteoporosis treatment including vitamin D. Interestingly, it has been demonstrated that the vitamin D is a potent stimulator of CYP19 (P450 aromatase gene) transcription [2]. Therefore, concomitant use of vitamin D and AI may lead to resistance to AI in postmenopausal women with hormone-receptor positive breast cancer. Further prospective studies are needed to confirm this proposal.



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References
1. Briest S, Davidson NE (2007) Aromatase inhibitors for breast cancer. Rev Endocr Metab Disord (2007 May 8) [Epub ahead of print]

2. Enjuanes A, Garcia-Giralt N, Supervia A, Nogues X, Ruiz-Gaspa S, Bustamante M, Mellibovsky L, Grinberg D, Balcells S, Diez-Perez A (2005) Functional analysis of the I.3, I.6, pII and I.4 promoters of CYP19 (aromatase) gene in human osteoblasts and their role in vitamin D and dexamethasone stimulation. Eur J Endocrinol 153:981?988

http://www.springerlink.com/content/hxx23183nlq378r9/fulltext.html

[AlaskaDenise]

Re: Cytokine Storm &amp; Vitamin D relationship?

It would seem there is some interaction between vitamin D, hormones; and osteoporosis & cancer risks.

It's interesting that there is a current clinical trial to study if Vitamin D can lessen the pain of aromatase inhibitors. After reading the above paper, I can help but wonder if the pain is lessened by the Vitamin D because it's undermining the actions of the aromatase inhibitors on the VDR.

The primary purpose is to determine if high dose vitamin D3 reduces the incidence of musculoskeletal symptoms associated with the aromatase inhibitor letrozole in women with early stage breast cancer and low serum vitamin D levels. The primary hypothesis is that high dose vitamin D3 prevents the worsening of musculoskeletal symptoms when compared to a standard dose vitamin D3 treatment.

http://clinicaltrials.gov/ct2/show/study/NCT00867217

If vitamin D plays such an important role in the production of estrogen, as proposed in the previous post, can you imagine all the processes it impacts?

.

[the doctor]

Re: Cytokine Storm &amp; Vitamin D relationship?

Recently I wrote Robert Heaney, MD and asked him look over a list of questions that we had been contemplating on this thread. Dr. Heaney is a recognized authority on bone and mineral metabolism who about a decade ago switched his focus to vitamin D. He is one of my teachers and granted me a great kindness for agreeing to seriously consider my rather simple questions and give me permission to share his responses with FT.

Grattan Woodson, MD




RH:
Grattan

Here are some tentative answers to your very interesting questions:

GW:
We are also debating what vitamin D replete means. Is there a serum level of 25 OH vit D3 that you think is "healthy"? What is the lower limit of serum 25 OH D3 that we clinicians should tolerate in our patients? (please express these answers in ng/ml. I am an ignorant country doctor and have trouble with mmol/l units)

RH:
The threshold is likely to be different for different systems/endpoints. For Ca absorption, the threshold is reached at about 32 ng/mL. Certainly the threshold for rickets is very low. In the Lappe et al cancer study, the median serum 25D was 31 ng/mL; those above that figure had a 60% lower risk of incident cancer than those below, suggesting a higher threshold for that outcome. On the other hand, John Aloia has just repeated his influenza trial, with negative results; it is likely ?though uncertain - that his controls were already relatively replete, making it difficult to see an effect of treatment. (See also below.)

GW:
We are also unsure what dose of vitamin D one should take as a supplement daily for optimal health meaning inclusive of bone health and immune system health.

RH:
At a recent workshop convened by CDC and AGS, the mean personal daily intake of the participating Vit D scientists was over 5000 IU. We find for our osteoporosis patients that 2000 IU/d suffices to get their 25D values up to 30 or higher. But we don?t have data on immune health. One RCT of TB treatment, published 3 years ago (Nursyam et al. 2006), used 10,000 IU/d (or placebo) in addition to standard anti-tubercular therapy. Sputum conversion for the placebo group was 77%, & 100% for the vitamin D group.

GW:
We are also uncertain whether one should supplement with vitamin D2 or D3

RH:
D3 by all means. It has about 4X the potency of D2 and is cheaper (not a Rx).

GW:
What is the fate of supplemental vitamin D3 given in excess of metabolic requirements? Is it stored in fat? Is it converted irrespective of needs to 25 OH vit D3?

RH:
Rapid conversion of D to 25D remains true, and probably occurs at serum D levels below the detection limit of the (D3) assay. However, several recent studies looking at tissue content indicate that about two-thirds of the body load of D at prevailing inputs is in the form of native D itself, and about one-third as 25D. The D is stored in both fat and muscle, while most of the 25D is in serum and liver. Serum levels of both rise as D inputs rise, but, above about 100 nmol/L, the rate of rise of D is twice as great as the rate of rise of 25D, suggesting saturation of the hepatic 25-hydroxylase. Most of the extra D is stored in fat at this point.

GW:
Is it safe to supplement with high dose vitamin D3? By high dose I mean 5,000iu to 10,000iu daily?

RH:
Yes. Hathcock et al (AJCN 2007) showed that 10,000 IU/d is the safe upper level. There are no reported cases of vit D intoxication at known daily intakes less than 30,000 IU, and no cases at serum 25D values below 200 ng/mL. (See also below.)

GW:
Is it safe to supplement with high dose vitamin D2? By high dose I mean 5,000iu to 10,000iu daily?

RH:
See above. We don?t use D2 at all.

GW:
We are also uncertain what a healthy level of 25 OH vit D3 is and what level will result in "optimal health".

RH:
This is a variant of the first question (about ?replete?). I think most working vit D scientists favor a value of 40 ng/mL or above. Bear in mind that average values of early Homo sp. in equatorial E. Africa would have been 60 or above, and values like that are common in fair-skinned outdoor workers at end of summer in Europe and N. America. A single, whole body MED dose of UV-B radiation gives a fair-skinned recipient about 15,000 IU. There has never been a case of vit D intoxication from sun exposure. Thus values in the range of 40 to 80 ng.mL have to be considered physiologic, and the oral doses required to achieve them (in lieu of sun exposure) should not be considered ?pharmacologic?.

GW:
What is the relationship between vitamin D and non-osseous disease, especially those within the auto-immune sphere?

RH:
The fully accurate answer is: we don?t know. But we do have pieces of an answer. The response to vit D supplementation in anti-TB Rx, cited above, is rapid and clinically meaningful. On the other hand, the action of vit D repletion in autoimmune disease seems to take place very early in life (in utero or in infancy). The famous Finnish experiment (2000 IU/d for all infants from birth to one year) (Hypponen et al. Lancet 2001), resulted in an astounding 88% reduction in type I diabetes by age 31. Congruent results have been reported for maternal 25D levels during pregnancy and adult onset diabetes and multiple sclerosis.

Hope this helps.
Regards,
Bob

Robert P. Heaney, M.D.
Interim Vice-President, Health Sciences
Creighton University, Omaha NE, 68178

[the doctor]

Re: Cytokine Storm &amp; Vitamin D relationship?

I am very appreciative for the time and thoroughness taken by Dr. Heaney to address some of the basic questions we have been asking on this thread. It is a real honor to have people of the stature and expertize of Dr. William Grant and Dr. Robert Heaney participate here with us in this discussion.

I hope that those following this very interesting conversation over the last few days have enjoyed it as much as I have. It has been very informative to me and before I got involved in this thread, thought I knew all about vitamin D!

Well, another notion of mine hits the dust.

At any rate while I think what Dr. Heaney said was pretty clear, I decided to paraphrase his responses in my own words. Below is my interpretation of what he said.

Specifically, he recommends supplementing with vitamin D3 rather than vitamin D2.

Second, he didn't say exactly what dose people should take but did say most vitamin D experts he knows take 5,000iu vitamin D3 daily.

Thirdly, he confirmed that doses up to 10,000iu per day are probably safe (but did not recommend that dose or any specific dose).

Fourth, he confirmed that having a 25 OH vit D3 serum goal of between 40ng and 80ng was reasonable to obtain both the bone benefits and probably those related to infection resistance and cancer prevention.

Finally, he expressed hope that there was a relationship between vitamin D and autoimmune diseases like MS and diabetes but thinks to get this benefit requires that the mother (and probably father too although we never consider him) of the child be vitamin D replete and otherwise well nourished before becoming pregnant.

Grattan Woodson, MD

[Shannon Bennett]

Re: Cytokine Storm &amp; Vitamin D relationship?

Dr. that answers most but not quite all of my questions. The only thing I/we still need to know is the dosage for children-how much, age limits, etc...

Dr. Woodson, I would like to extend our overwhelming gratitude to you and to Dr. Heaney.

[kiwibird]

Re: Cytokine Storm &amp; Vitamin D relationship?

I second that Shannon. Your advice and knowledge has been invaluable. Thank you.

[the doctor]

Re: Cytokine Storm &amp; Vitamin D relationship?

Dr. that answers most but not quite all of my questions. The only thing I/we still need to know is the dosage for children-how much, age limits, etc...

Dr. Woodson, I would like to extend our overwhelming gratitude to you and to Dr. Heaney.

Shannon, thanks for the kind comments.

I am not a pediatrician but do know that those involved in pediatric medicine have been reconsidering this issue.

I think the RDA for kids remains pretty low, 200iu but no more than 400iu of D2.

So, I don't have an answer for you about this but would speculate that kids need a lot more than these levels of D3 as a supplement for optimal health especially those who do not get adequate sun exposure due to where or how they live.

GW

[AlaskaDenise]

Re: Cytokine Storm &amp; Vitamin D relationship?

Thank you Dr. Woodson and Dr. Heaney.

I really appreciate your willingness to share your time and expertise on this subject.

Regarding children, in past generations there was a tradition of giving a baby a daily "sunbath" of 15+ minutes - for good health. It also helps clear up diaper rash.

.