Cytokine Storm & Vitamin D relationship?

[The Mountains Voice]

Re: Cytokine Storm & Vitamin D relationship?

Perhaps we could do a poll of our own members and find out who was taking Vitamin D supplements and whether symptoms were severe or indeed if they caught the flu at all.

1st I would like to say that this has been an amazingly informative thread - and I definitely think that some study should be devoted to this.

2nd, My story is actually the 1st story listed in Niman's Thread about Member Symptoms (Can't find it - can't remember exact name). Don't know if I included this - but my wife is sort of a research freak on homeopathic and natural cures. I forwarded her this thread, and she just told me something I didn't know. When my son and I became ill - she was just tailing up about 3 weeks of taking Vitamin D Supplements & Ginseng. She's adamant I include that Ginseng part She is also adamant about my including the fact she took higher doses of C than normal.

She was covered in the virus between me and my 5 year old exposing her. Yet she had little to no obvious symptoms. She felt a little more nauseous, slight headache, and was more tired - but other than that you wouldn't know she had the flu.

I will say that at the time I thought it pretty darn miraculous that she didn't catch what we had - which to this day I am convinced was an early wave of H1N1 (mid April I think?)

Anyway - can't determine anything from this really - but it is ONE sample. For the record she was only taking 200 - 400iu supplement through Calcium tablets - but it was an abnormal fact for her to even be taking that. Which is why she remembers it so clearly. She's one of these human guinea pigs - always testing

 

[the doctor]

Re: Cytokine Storm & Vitamin D relationship?

I wish to thank Dr. Grant for being so kind to visit this thread but since he is already a member of the FT community, why shouldn't he.

Anyway it is pretty great to have the author of a contemporary paper of such potential import partcipate with us in the discussion.

I recall recently gsgs making a comment on how discussions like this could become a replacement or supplement to the peer review process. While I think he is right about the significance of discussing issues like this in a public forum open to all is a terrific idea, it does not replace the peer review process.

What the peer review process amounts to is the requirement of the author to run his paper past an editor initially then a set of reviewers who are chosen by the editor usually but not always because they have demonstrated expertize in the topic presented in the scholarly article.

At any rate I can attest to what a long and arguous task this can be and one that for me at least has not always resulted in success.

In summary then, what a pleasure to have Dr. Grant share his views and insights on this very interesting and topical issue. My hat is off to you and your collaborators.

http://www.flutrackers.com/forum/images/smilies/tiphat.gif

Well done!

Grattan Woodson, MD

 

[The Mountains Voice]

Re: Cytokine Storm & Vitamin D relationship?

Another interesting statistic was the flu patients who were sequestered in canvas tents in New York during the 1918 pandemic, had a much better chance of surviving than did those who found room in the hospital wards. Whether this was due to vitamin D finding its way thorough the woven tent or for some other reason is unknown but, it is an interesting hypothesis.

I've read this entire thread, and it does seem that there is a very strong correlation here. And then a thought popped into my head - perhaps part of the "holy grail" answer as to why Flu Spreads Seasonally.

Could a part of it simply be sunlight / D related?

It does fit as a solid part of the facts equation.

Perhaps officials should add that into their research charts / questions.....
In all cases, track lifestyle patterns that could indicate greater or less sunshine exposure / D intake.

 

[the doctor]

Re: Cytokine Storm & Vitamin D relationship?

I've read this entire thread, and it does seem that there is a very strong correlation here. And then a thought popped into my head - perhaps part of the "holy grail" answer as to why Flu Spreads Seasonally.

Could a part of it simply be sunlight / D related?

It does fit as a solid part of the facts equation.

Perhaps officials should add that into their research charts / questions.....
In all cases, track lifestyle patterns that could indicate greater or less sunshine exposure / D intake.

That is an interesting suggestion. As I would interpret what you are saying is during the winter months when sunshine exposure is lower, this would be predicted to result in lower winter vitamin D levels compared with those in the summer.

The lower levels of vitamin D during this time would result in an immune system "fitness penalty" to borrow from our influenza lexicon.

This would make humans as a group more susceptible to influenza and other infections resulting in them having a higher incidence during this season of the year than in others.

Anyway, I like it big guy. I agree with you too that it probably is "one of the reasons"l

More importantly IMO it is one of the things we can do something about. Something that is not costly, is widely available both for free (sunlight) or at modest cost (OTC Vit D2 and D3. Vitamin D obtained in these ways has a low potential for toxicity even when take in doses many times the RDA.

All these factors have positive influences from both a health risk vs health benefit and a cost vs benefit prospective.

Nice observation TMV.

Grattan Woodson, MD

 

[St Michael]

Re: Cytokine Storm & Vitamin D relationship?

The Vitamin D - influenza link was proposed several years ago by Dr. John Cannell.

See Epidemic Influenza And Vitamin D

 

[St Michael]

Re: Cytokine Storm & Vitamin D relationship?

Epidemiol Infect. 2006 Dec;134(6):1129-40. Epub 2006 Sep 7.

Epidemic influenza and vitamin D.
Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, Giovannucci E.

Atascadero State Hospital, 10333 El Camino Real, Atascadero, CA 93422, USA. jcannell@dmhash.state.ca.us

In 1981, R. Edgar Hope-Simpson proposed that a 'seasonal stimulus' intimately associated with solar radiation explained the remarkable seasonality of epidemic influenza. Solar radiation triggers robust seasonal vitamin D production in the skin; vitamin D deficiency is common in the winter, and activated vitamin D, 1,25(OH)2D, a steroid hormone, has profound effects on human immunity. 1,25(OH)2D acts as an immune system modulator, preventing excessive expression of inflammatory cytokines and increasing the 'oxidative burst' potential of macrophages. Perhaps most importantly, it dramatically stimulates the expression of potent anti-microbial peptides, which exist in neutrophils, monocytes, natural killer cells, and in epithelial cells lining the respiratory tract where they play a major role in protecting the lung from infection. Volunteers inoculated with live attenuated influenza virus are more likely to develop fever and serological evidence of an immune response in the winter. Vitamin D deficiency predisposes children to respiratory infections. Ultraviolet radiation (either from artificial sources or from sunlight) reduces the incidence of viral respiratory infections, as does cod liver oil (which contains vitamin D). An interventional study showed that vitamin D reduces the incidence of respiratory infections in children. We conclude that vitamin D, or lack of it, may be Hope-Simpson's 'seasonal stimulus'.

 

[The Mountains Voice]

Re: Cytokine Storm & Vitamin D relationship?

Nice observation TMV.

The Vitamin D - influenza link was proposed several years ago by Dr. John Cannell.

See Epidemic Influenza And Vitamin D

Thanks Doc. And I wanted to comment on Dr. Grant's paper I just downloaded and reviewed - which also pretty much directly makes these observations as well (I just got lucky - but this guy has the data!). Dr. Grant has it posted online at the following page.....
http://www.landesbioscience.com/journals/dermatoendocrinology/article/9063

You have to log in (free) to read it, but I've downloaded it and attached it to this post in a PDF. It really is good reading. Dr. Grant you write well for a science guy - you folks normally lose me a few words in LOL

Anyway - a very good read.

And in regards to St Michaels link above - VERY informative and thought provoking as well.

I agree with Doc - this is something that is exciting - because WE CAN DO SOMETHING ABOUT THIS!!

I think this whole subject is grounds for an informational press release.

And by golly - I'm going to the pool tomorrow!

PS.... I still suggest everyone read attached PDF, and check out story in Epidemic Influenza And Vitamin D.

 

[the doctor]

Re: Cytokine Storm & Vitamin D relationship?

Cartski asked:
"How can one measure how full the tank is? How can one measure deficiency?"

As suggested by other posters, the best way to do this is by checking the 25 hydroxyvitamin D3 level AKA 25 OH vit D3. While indirect, it is the easiest and least costly way to measure tissue stores of vitamin D2.

What is interesting about this relationship is that it is exponential rather than linear. This means that a 25 OH vit D3 level of 20ng indicates a level of stored vitamin D2 that is 10 times higher than a 25 OH vit D3 level of 10ng.

So this means that a bone healthy 25OH Vit D3 level between 50 ng and 60ng means that the vitamin D2 present in storage is about 500,000 times as great as that present when the vitamin D2 level is 10ng.

The reason for this is that vitamin D2 found in the circulation is rather quickly scoffed up by the fat tissue when it is in excess of need. This results in a short serum half-life but a long tissue half-life. The fat tissue preserves the vitamin D2, keeping it fresh. When needed in the future, vitamin D2 is released into the blood where it is converted via several steps to 25 OH vit D3.

I think vitamin D3 might be more accurately seen as an intermediate pre-hormone metabolite that can be produced via UV light or via conversion of Vitamin D2 to D3.

Once vitamin D3 is formed, it appears to rapidly be converted by the liver to 25 OH vit D3. So it too has a short half-life.

I don't recall the half-life of 25 OH Vit D3, maybe someone can chime in here.

Grattan Woodson, MD

 

[The Mountains Voice]

Re: Cytokine Storm & Vitamin D relationship?

jcannell@dmhash.state.ca.us

I hope his email is current. I just sent him a link to the thread, and asked him to participate. This subject needs more discussion.

 

[kiwibird]

Re: Cytokine Storm & Vitamin D relationship?

PS.... I still suggest everyone read attached PDF, and check out story in Epidemic Influenza And Vitamin D.
Attached Files
File Type: pdf VitaminD-CytokinePaper.pdf (645.1 KB, 0 views)
Edit/Delete Message

Thank you for the link Mountainsvoice and Dr Grant for the paper, obviously. Extremely interesting reading. Does Vitamin D have an effect on the bacterial load then?

 

[the doctor]

Re: Cytokine Storm & Vitamin D relationship?

cartski asked:

If D is synthesized when a person is exposed to sunlight, could not dosage + sunlight could produce a whopping amount"?

Yes it could but this is not usually something we see clinically.

Dr. Robert Heaney and colleagues at Creighton University in Iowa did an interesting study of 25 OH vit D3 levels (personal communication at a meeting but this was years ago and was probably been published back then). They opined that roofers who worked in the summer with their shirts off would have higher than common vitamin D levels. What they found was that these people had 25 OH vit D3 levels in the 150ng range with no signs if high calcium levels or of any toxicity.

He also described vitamin D2 dosing studies where very high daily doses (up to 50,000iu/day) of vitamin D2 were given to volunteers for various lengths of time.

One finding that was of interest to me was those treated at even the highest level of vitamin D2 rarely displayed 25 OH vit D3 levels much higher than 100ngs.

These are interesting observations and are consistent with my anecdotal experience with giving high doses of vitamin D2 to patients suspected of having low grade prostate cancer. I could never get their serum 25 OH vit D3 level much above 100ng even when they took 50,000iu daily for several months.

Grattan Woodson, MD

 

[the doctor]

Re: Cytokine Storm & Vitamin D relationship?

For whatever its worth, here are some interesting comments from Dr. Mercola on Vitamin D. (I don't give him much credence either way, but I'm inclined to think he has a point regarding Vitamin D3):

Vitamin D3 Supplemental vitamin D comes in two forms: ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3).

They have generally been regarded as equivalent and interchangeable, but that notion is based on studies of rickets prevention in infants conducted seven decades ago.

Recent studies have shown that vitamin D3 is a more potent form of vitamin D. Vitamin D2 has a shorter shelf life, and its metabolites bind with protein poorly, making it less effective. One unit of cod liver oil (containing vitamin D3) has been shown to be as effective as four units of Viosterol (a medicinal preparation of vitamin D2).

However, the form of vitamin D used in prescriptions in North America is almost invariably vitamin D2.

Sources: American Journal of Clinical Nutrition October 2006; 84(4): 694-697


Dr. Mercola''s Comments

Basically there are two types of oral vitamin D supplements. The natural ones are D3, and they contain the same vitamin D your body makes when exposed to sunshine. The synthetic ones are vitamin D2, which are sometimes called ergocalciferol.

Once either form of the vitamin is in your body, it needs to be converted to a more active form. Vitamin D3 is converted 500 percent faster than vitamin D2. Interestingly, it was previously thought that the kidney exclusively performed this function, as least that is what I was taught in med school.

However, in 1998 Dr. Michael Hollick, the person who discovered activated vitamin D, showed that many other cells in your body can make this conversion, but they use it themselves, and it is only the kidney that makes enough to distribute to the rest of your body.

While there have been no clinical trials to date demonstrating conclusively that D2 prevents fractures, every clinical trial of D3 has shown it does.

However, nearly all the prescription-based supplements contain synthetic vitamin D2, which was first produced in the 1920s through ultraviolet exposure of foods. The process was patented and licensed to drug companies for use in prescription vitamins. In case you didn't know, the vitamin D that is added to milk is NOT D3 but the highly inferior vitamin D2.

The study linked above concluded that "vitamin D2 should no longer be regarded as a nutrient appropriate for supplementation or fortification of foods."

That being said, optimizing your sun exposure and levels of vitamin D3 may, indeed, be one of the most important physical steps you can take in support of your long-term health. Conventional medicine is finally beginning to get on board the vitamin-D3 bandwagon, using the natural power of sunshine to treat type 2 diabetes, osteoporosis during a woman's pregnancy and even tuberculosis.

It is important to understand that the ideal and STRONGLY preferred method of increasing your vitamin D3 level is through appropriate sun exposure. I really do not advise oral supplements, not even cod liver oil now, UNLESS you can have your blood levels regularly monitored.

It just is too risky. I have seen too many potentially dangerous elevations of vitamin D levels, including my own, from those that are taking oral supplements.

But when you get your vitamin D from appropriate sun exposure your body can indeed self-regulate and greatly reduce vitamin D production if you don't need it, which makes it very difficult to overdose on vitamin D from sun exposure.

Thanks St. Michael for this contribution.

I am framiliar with Dr. Mecola and have read his book concerning the pandemic hoax.

There is a lot to say about the contents above. First the observation that vitamin D3 is rather rapidly converted to 25 OH vit D3 is of interest and probably explains why it has such a short serum half-life.

I wonder, if someone like a roofer as described by Dr. Heaney above has very high vitamin D3 production from the sun, would the excess be stored in the tissue (fat or somewhere else like muscle) or would there be an obligate conversion of excess vitamin D3 to 25 OH vit D3 irrespective of needs?

Grattan Woodson, MD

 

[gsgs]

Re: Cytokine Storm & Vitamin D relationship?

http://www.ncbi.nlm.nih.gov/pubmed/...nel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
...further research needed...

doesn't sound encouraging. Why can't they prove it ?

 

[the doctor]

Re: Cytokine Storm & Vitamin D relationship?

While it is possible to make plenty of vitamin D3 with enough sun exposure, there is a cost to taking this approach. Prolonged sun exposure damages the skin and increases risk for skin cancers and melenoma, especially in fair skinned people.

I would prefer to fill my tank with synthetic oral vitamin D2 and skip the excessive sun exposure.

This does not mean that I do not agree that vitamin D3 is converted much faster to activated 25 OH vit D3 than is vitamin D2. It certainly is but what I wonder; is it necessary to take vitamin D3 as the supplement or via UV exposure or is it simply good enough or perhaps even better to get your vitamin D as the storage form, vitamin D2.

I think that as long as your vitamin D storage tank is adequately filled, when there is a need for more active vitamin D, the stored D2 is released, converted to D3 and then rapidly transformed into activated 25 vit D3 along with all those fascinating other forms of activated vitamin D that target the immune system rather than bone and calcium metabolism, i.e; "the useless brethren of 25 OH vit D3 produced by the liver.

Grattan Woodson, MD

 

[gsgs]

Re: Cytokine Storm & Vitamin D relationship?

how long does it take to fill your tank ?

correlate flu in cities with #sunny days, the data is available

 

[wbgrant]

Re: Cytokine Storm & Vitamin D relationship?

Hi,
Interesting discussion. Here are a few additional comments.

1 - The half life of vitamin D and 25(OH)D in the body is about 4-6 weeks. Thus, vitamin D made in summer can last into the fall, but not winter.

2 - UVB produces vitamin D but UVB and UVA out to 330 nm also destroys some of the vitamin D metabolites. This is why the maximum amount of vitamin D that can be produced per day with whole body exposure is about 10,000 IU. That much can be made in a few minutes by a young person with pale skin on a bright summer's day.

3 - There is good evidence that vitamin D, through production of human cathelicidin, LL-37, reduces the risk of several viruses including seasonal influenza, the common cold, Epstein-Barr virus, and others, and bacteria such as TB, vaginal bacteria, bacteria involved in septicemia, pneumonia bacteria, etc. What has not been shown is that vitamin D and LL-37 had any impact on the A/H1N1 pandemic virus of 1918-19. On the other hand, A/H1N1 in recent times has been seasonal, implying that vitamin D/LL-37 probably played an important role in combating it.

4 - Cold temperature can also play a role in susceptibility to respiratory viral infections. Respiratory syncytical virus, often the cause of bronchitis, is more related to cold air than vitamin D. Cold temperature shuts down the capillaries in the respiratory system, so white blood cells, etc., can't get to the surface to attack the virus. This may play a role in influenza as well.

 

[the doctor]

Re: Cytokine Storm & Vitamin D relationship?

http://www.ncbi.nlm.nih.gov/pubmed/...nel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
...further research needed...

doesn't sound encouraging. Why can't they prove it ?

Diseases: A Systematic Review of Randomized Controlled Trials.
Abstract

Yamshchikov AV, Desai NS, Blumberg HM, Ziegler TR, Tangpricha V.
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA 30303.
Objective Vitamin D is the precursor to a steroid hormone primarily known for its role in regulating calcium homeostasis and skeletal health. Vitamin D also has non-skeletal functions that may play a role in susceptibility to various infectious and autoimmune conditions. Despite recent advances in understanding of the non-classical functions of vitamin D, little information is available regarding their clinical relevance for patient care. We review the existing human controlled intervention studies of vitamin D as adjunctive therapy in settings of infection, and provide recommendations for design and implementation of future studies in this field based on the evidence reviewed.Methods We conducted a systematic review of randomized controlled clinical trials that studied vitamin D therapy for treatment or prevention of infectious diseases in humans. Studies from 1948-2009 were identified through search terms in PubMed and Ovid.Results Thirteen controlled trials were identified by our search criteria. Ten trials were placebo controlled, and nine of the ten were conducted in a rigorous double-blind design. The selected clinical trials demonstrated significant heterogeneity in terms of baseline patient demographics, sample size, and vitamin D intervention strategies. Serious adverse events attributable to vitamin D supplementation were rare across all studies. Based on studies reviewed to date, the strongest evidence supports further research into adjunctive vitamin D therapy for tuberculosis, influenza, and viral upper respiratory illnesses. Aspects of study design are highlighted for the selected studies to help guide future clinical research in the field.Conclusions More rigorously designed clinical trials are need to further evaluate the relationship between vitamin D status and the immune response to infection, and to delineate necessary changes in clinical practice and medical care of patients with vitamin D deficiency in infectious disease settings.


I need to read the whole article not just the abstract to understand this communication.

Given that I do not know what these authors have presented or proposed, I will venture to make a few comments. While academically risky, I have moved beyond those concerns so here goes.

If vitamin D2 was used therapeutically in very ill people as a rescue treatment then it might not have been able to be converted to vitamin D3 fast enough to make a difference.

If there was a consensus that vitamin D3 was rapidly converted to 25 OH vit D3 and its immune stimulating brethren, then if I were considering use of vitamin D as a rescue therapy of someone with severe influenza for instance, then giving them vitamin D3 instead of vitamin D2 would be more likely, IMO to result in a higher level of the desired immune potent activated forms of vitamin D produced by the liver.

It is unlikely that those acutely ill with an infectious disease would benefit if treated acutely with previously activated forms of vitamin D including 25 OH vit D3 or 1,25 OH2 vit D3 since both are products destined for a role in calcium metabolism. It is the activated vitamin D products produced by the liver other than 25 OH vit D3 that play the greatest immune system role IMO and it is those therefore that would be likely to have the greatest immediate benefit in the acutely ill patient.

While there have been comments above about the non-renal intercellular conversion of 25 OH vit D3 to 1,25 vit D3 and the activity of this terminal hormone, IMO what is likely is that it plays different roles in different tissues.

The immune competent vitamin D products are not the ones we measure routinely in the clinic with assays commercially available from Quest or Lab Corp. They can only be measured today in research labs who have developed specific techniques to do so. The methods to do this are well established in the bone literature and probably elsewhere by now given our new found interest in these compounds.

So, when I find this article in its complete form, these concerns will be foremost in my mind. If they are not considered, then it may be that I will discount this work as definitive but not necessarily as informative. All work done in an objective fashion have value. The author's interpretation of the results are not always the key point of the work.

GW

 

[gsgs]

Re: Cytokine Storm & Vitamin D relationship?

it should be possible to show connection with weather

first show a connection of weather in the last 4-6 weeks and
how full the D-Tank is (assuming Vitamin-D level in a person
can be easily measured ?)

then compare with seasonal ILI-data

 

[the doctor]

Re: Cytokine Storm & Vitamin D relationship?

Hi,
Interesting discussion. Here are a few additional comments.

1 - The half life of vitamin D and 25(OH)D in the body is about 4-6 weeks. Thus, vitamin D made in summer can last into the fall, but not winter.

2 - UVB produces vitamin D but UVB and UVA out to 330 nm also destroys some of the vitamin D metabolites. This is why the maximum amount of vitamin D that can be produced per day with whole body exposure is about 10,000 IU. That much can be made in a few minutes by a young person with pale skin on a bright summer's day.

3 - There is good evidence that vitamin D, through production of human cathelicidin, LL-37, reduces the risk of several viruses including seasonal influenza, the common cold, Epstein-Barr virus, and others, and bacteria such as TB, vaginal bacteria, bacteria involved in septicemia, pneumonia bacteria, etc. What has not been shown is that vitamin D and LL-37 had any impact on the A/H1N1 pandemic virus of 1918-19. On the other hand, A/H1N1 in recent times has been seasonal, implying that vitamin D/LL-37 probably played an important role in combating it.

4 - Cold temperature can also play a role in susceptibility to respiratory viral infections. Respiratory syncytical virus, often the cause of bronchitis, is more related to cold air than vitamin D. Cold temperature shuts down the capillaries in the respiratory system, so white blood cells, etc., can't get to the surface to attack the virus. This may play a role in influenza as well.

Thanks Dr. Grant. These comments make a lot of sense.

We often see patients with osteoporosis who have adequate levels of 25 OH D3 in the summer but who become deficient in the winter.

If these people were provided with adequate supplements of vitamin D2 (both in respect to "filling their tank" and in an ongoing basis perhaps at the level of 10,000iu dosage per day, do you care to speculate on what the effect of this approach might have on both the circulating levels of 25 OH vit D3 as well as those of the immune competent forms of activated vitamin D produced by the liver?

GW

 

[cartski]

Re: Cytokine Storm & Vitamin D relationship?

I need to read this thread more carefully. However, here's a nice review of the literature, I believe:

http://www.cfp.ca/cgi/reprint/53/5/841

J.