Cytokine Storm & Vitamin D relationship?

[Shannon Bennett]

Re: Cytokine Storm & Vitamin D relationship?

Thank you for your response. You write clearly enough for layman (at least this one) to easily understand your last post.

Next question. You knew there would be a few more at least lol. Would it be prudent then for people to add D supplements to their routines if they felt fairly confident they were healthy and after taking a test to see they had at least some D in their systems? My assumption is that people with extremely low, or nonexistent levels might assume they are immune compromised. Others could without fear add D to keep their tanks full.

Next question. How to determine those who are deficient due to disease or simply not out in the sunlight enough? How long does it take for someone to take vitamin D and have it show up on a test? How much would you have to take to quickly see if you were benefiting?

[prepdeb]

Re: Cytokine Storm & Vitamin D relationship?

Another thank you for Palbert!

As I understand your response, many people with chronic health issues that compromise their immune systems probably have low vitamin D levels by design.
Natures way of maintaining balance.
Upsetting that balance is not a good idea.

A dear friend of mine has lupus and tries to avoid too much time in the sun, but she loves her motorcycle and her garden. Not easy to balance.

Thanks to kiwibird for making me feel less dense ... LOL!

[Shannon Bennett]

Re: Cytokine Storm & Vitamin D relationship?

Tom, obviously you do not avoid D if you are suffering from rickets. He is specifically referring to auto-immune diseases. The vast majority of the population would not have a problem with supplementation.

[prepdeb]

Re: Cytokine Storm & Vitamin D relationship?

There's a list of over 100 autoimmune diseases here

Geez, nearly everyone I know has at least one of them.

http://www.squidoo.com/list_of_autoimmune_diseases

[kiwibird]

Re: Cytokine Storm & Vitamin D relationship?

However, bacteria create ligands, which like 25-D, inactivate the VDRThe Vitamin D Receptor. A nuclear receptor located throughout the body that plays a key role in the innate immune response. and, in turn, the innate immune responseThe body's first line of defense against intracellular and other pathogens. According to the Marshall Pathogenesis the innate immune system becomes disabled as patients develop chronic disease.. This allows the microbes to proliferate. In response, the body increases production of 1,25-D from 25-D, leading to one of the hallmarks of chronic inflammatory disease: a low 25-D and a high 1,25-D.

This pattern is a result of the disease process rather than a cause. For a variety of reasons, neither increased consumption of vitamin D nor the body's synthesis of additional 1,25-D is ultimately effective at combating infection.

So either the body is overwhelmed by the disease (and I gather bacteria and viruses cause the same response) - wouldn't this mean that immunocompromised people who do not have enough vit d (because the body has "decided" this is not a good idea - should be overwhelmed by the disease (is there another mechanism within the body to deal with disease)) or

As mentioned before, exposure to injury and infection enhances production of 1,25-D, ......
However, certain feedback mechanisms are also in place, which allow the body to limit the production of 1,25-D to just that amount needed for proper transcriptional activation of the VDR...
*
When the VDR.... is activated, it transcribes the gene for the enzyme CYP24A1, which inactivates conversion of 25-D into 1,25-D.
*
An activated VDRT...... also controls 1,25-D concentration by limiting transcription of the gene CYP27B1, which converts 25-D into 1,25-D.6

the body produces way to much 1-25d and a cytokine storm causes a self destructive reaction.

Doesn't this

However, bacteria create ligands, which like 25-D, inactivate the VDRThe Vitamin D Receptor.

Balance the overactivation... yes I think I have answered my own question - if a patient is not immunocompromised.


I gather not all bacteria are able to deregulate the vdr - would this be the same for viruses. If this were the case, wouldn't whether a cytokine storm developed depend on the virus involved, and possibly the secondary bacterial agent involved as well?

Also - apologies I know I am asking a lot of questions but can't help myself" if an immunocompromised person is well and have an ordinary persons optimal amount of active and inactive vitamin d, wouldn't that give them a head start on dealing with the virus or bacteria in the first place?

And all of this is based on the presumption that there is a cause and effect rather than effect and cause, ie disease and high vit 1-25,d.

If a patient was immunocompromised and

It is widely assumed that low levels of 25-D cause or exacerbate disease. But what if it was the other way around? What if the body was acting in the most sane, logical manner it could and choosing to downregulate (that is the right word) levels of 25-D so as to upregulate immune function?

this was the logical course of events, surely the patient wouldn't be immunocompromised. ie - because the body is not functioning properly and causing this compromised state, surely we can assume that it is not functioning properly by causing low levels of Vit d to be stored.

Do all immune problems react the same way with regard to Vitamin D hormones?

Many thanks for your patience.

[kiwibird]

Re: Cytokine Storm & Vitamin D relationship?

And - obviously - not everyones vdr is the same:

Prevalence of vitamin D receptor gene polymorphism in a Uruguayan population and its relation to type 1 diabetes mellitus

http://www.funpecrp.com.br/GMR/year2...full_text.html

[palbert]

Re: Cytokine Storm & Vitamin D relationship?

Wow, lots of comments and questions.

Prepdeb said: "I have mild COPD and hepatitis C. I've been battling illness for the past month or so, with each return being milder than the previous. Into my third round of whatever is causing the flu-like symptoms. Does this mean supplementing with vitamin D would be detrimental? I'm assuming it would be alright to supplment when not ill."

That's what we're saying. You raise an interesting point though. Is it really the symptoms that are a problem? What if I could make a convincing case that the symptoms are an indication that your body is (successfully) fighting off a viral infection? This question matters when you consider the fact that vitamin D likely suppresses the immune response. In that case, vitamin D is not something you would want to give a person fighting an infection ? even if your symptoms make you feel temporarily worse....

***

Shannon said: "Would it be prudent then for people to add D supplements to their routines if they felt fairly confident they were healthy and after taking a test to see they had at least some D in their systems? My assumption is that people with extremely low, or nonexistent levels might assume they are immune compromised. Others could without fear add D to keep their tanks full."

I disagree. If you read my previous comment, I also might take issue with the concept that a person has a vitamin D "tank." We are talking about a secosteroid with multiple forms that the body takes great pains to carefully manage. (More about this later in this post.) Introducing huge amounts of vitamin D into the system is historically and evolutionarily unprecedented. Contrary to conventional wisdom, it seems unlikely that our Neolithic ancestors got 10,000 IUs of vitamin D.

***

Prepdeb said: "A dear friend of mine has lupus and tries to avoid too much time in the sun, but she loves her motorcycle and her garden."

Photosensitivity is much more common in patients suffering from autoimmune and other chronic diseases than most people realize. For people who advocate vitamin D supplementation, this observation is difficult to explain.

***

Tolenio said: "So people suffering rickets should avoid sunshine, and oral vitamin D supplementation, and there should be an RDA for vitamin D of 0 (zero)?"

Vitamin D supplementation appears to affect different people in different ways. For healthy people with no vitamin D dysregulation, vitamin D supplementation does not appear to have any substantial impact. But for people who are sick, it's quite a different matter. Practically speaking, we would argue that people can get enough vitamin D from a normal diet such as the kind people have been eating for tens of thousands of years.

***

Toloneio said: "Also the notes of doctors from the 1918 pandemic which indicated patients left in the open air and sunshine doing better than those housed otherwise should be ignored?"

Good question.
* Maybe those patients weren't exposed to additional nosocomial infections.
* Vitamin D hadn't been added to the food chain yet - no baby formula, no supplemented orange juice, no pre-natal vitamins, etc. Today, very few, if any people would have that naturally low a level of 25-D (except if it's downregulated in the case of disease). It's not the same circumstances, because the starting levels of 25-D in the body is very different than it was in 1918.
* In people who have naturally low levels of vitamin D, the body appears to benefit from a one-time bolus of vitamin D. Vitamin D3/D2 gets converted into 25-D. 25-D is converted into 1,25-D. But, like I said before, if there's too much 1,25-D, it can affect the antimicrobial activity of other nuclear receptors that also play important roles in innate immune function.


***

Shannon said: "Tom, obviously you do not avoid D if you are suffering from rickets. He is specifically referring to auto-immune diseases. The vast majority of the population would not have a problem with supplementation."

I'm sorry to be controversial, but... Tom was right: we are casting a fairly wide net, one which includes the autoimmune diseases as well as chronic inflammatory diseases. We point to work - not even our own - which strongly suggests that the primary factor which causes rickets is not vitamin D "deficiency." That work is summed up here:

http://mpkb.mp-dev.com/doku.php/home:diseases:rickets

With regard to food supplementation policy, I would argue that the real question is not how much vitamin D does a person need to have a sufficient amount of 25-D. 25-D is the inactive form of vitamin D; it turns off the Receptor. The real question is, "How much vitamin D does a person need to have enough 1,25-D?" In this case, the answer for most people is that they have plenty of vitamin D.

This is validated by observational studies which show that populations that avoid vitamin D remain healthy despite low levels of vitamin D. See here:

http://mpkb.mp-dev.com/doku.php/home:pathogenesis:vitamind

Though this isn't always the case she probably has high levels of 1,25-D. Look at Dr. Blaney's lovely graph (peer-review publication in press) which plots 25-D against 1,25-D:

http://mpkb.mp-dev.com/doku.php/home:pathogenesis:vitamind:metabolism

***

Kiwibird said: "I gather not all bacteria are able to deregulate the vdr - would this be the same for viruses. If this were the case, wouldn't whether a cytokine storm developed depend on the virus involved, and possibly the secondary bacterial agent involved as well?"

We would discount the idea that the deaths from the '18 pandemic were caused by a cytokine storm or the like. Andrew Noymer has made a persuasive case that deaths from the Spanish Flu were primarily a result of co-morbidity with another infectious pathogen, namely tuberculosis: http://www.demog.berkeley.edu/~andre...R_1918_flu.pdf

Kiwibird said: "if an immunocompromised person is well and have an ordinary persons optimal amount of active and inactive vitamin d..."

I disagree with the premise of this question. Immunocompromised people aren't well.

Kiwibird said: "And all of this is based on the presumption that there is a cause and effect rather than effect and cause, ie disease and high vit 1-25,d."

Yup.

Kiwibird said: "Do all immune problems react the same way with regard to Vitamin D hormones?"

To the balance of chronic inflammatory diseases, yes.

Best,
Paul

[kiwibird]

Re: Cytokine Storm & Vitamin D relationship?

On Submariners:

Absence of sunlight: The importance of solar-produced vitamin D was underscored in a study that evaluated vitamin-D status in a submarine crew after two months of acute sun deprivation. Although the crew consumed a vitamin-D fortified diet, their levels of this nutrient plummeted.

These sailors are healthy people. They did not all become unhealthy whilst in the submarine, they just went without sunlight.

http://aquilinefocus.blogspot.com/2006/05/submarine-relativity-facts-did-you.html

Abstract;Blood and urine biochemical markers of vitamin D and bone metabolism were analyzed in the crew of a Japanese diesel-electric submarine before and after a four-week patrol cruise, to investigate the influences of a sunlight-deprived environment on vitamin D homeostasis and bone metabolism. Subjects were 20 crew members (aged from 21 to 41 years with a mean.+-.SD of 28.1.+-.5.1 years) of a "Yushio" Class diesel electric submarine. Blood and urine specimens taken from the subjects before and after the patrol were compared. There were no signs or symptoms caused by the abnormal calcium or vitamin D metabolism among the subjects during and after the cruise. However, serum calcium and phosphorus increased remarkably, and 25-hydroxy-vitamin D (25(OH)D), urinary phosphorus, pyridinorine (Pyr) and deoxy-pyridinorine (d-Pyr) showed significant decreases after the patrol, while levels of 1,25-dihydroxyvitamin D (1,25(OH)2D) and urinary calcium were unchanged. There was a significant positive correlation between the change of 25(OH)D concentration and age; the decrease of 25(OH) D tended to be larger in the younger subjects. According to the result that the concentration of 1,25(OH)2D was well preserved despite the significant decrease of its precursor, 25(OH)D, some compensation mechanisms, such as activation of renal enzymes, for the decreased cutaneous vitamin D synthesis due to deprived UV irradiation was considered to be established within one month. (author abst.)

http://sciencelinks.jp/j-east/articl...04A0158510.php

[sharon sanders]

Re: Cytokine Storm & Vitamin D relationship?

Hi,

I am interested in this divergence between Trevor Marshall and the World Health Organization;



Trevor Marshall on the same topic;


Additional sunlight would appear to come under the classification of supplementation of vitamin D. In the light of decades of research why this divergence between the WHO and Marshall?

Tom

We are not concerned about the why of the divergence between the WHO and Marshall. We present data and people decide for themselves.

[sharon sanders]

Re: Cytokine Storm & Vitamin D relationship?

Welcome Paul!

Thank you for your time and expertise.

[kiwibird]

Re: Cytokine Storm & Vitamin D relationship?

It is widely assumed that low levels of 25-D cause or exacerbate disease. But what if it was the other way around? What if the body was acting in the most sane, logical manner it could and choosing to downregulate (that is the right word) levels of 25-D so as to upregulate immune function? If this were true, giving a patient additional vitamin D, whether it is D2 or D3, would be doing the exact thing our body would have us not do. In other words, we're saying you give an immunocompromised patient supplemental vitamin D, and you are making him more immunocompromised.

From your post above and

Kiwibird said: "if an immunocompromised person is well and have an ordinary persons optimal amount of active and inactive vitamin d..."

I disagree with the premise of this question. Immunocompromised people aren't well.

Then why would you assume that a sick body is making a sensible "decision" by lowering Vitamin D levels.

[AlaskaDenise]

Re: Cytokine Storm & Vitamin D relationship?

Paul:

Thank you for sharing your valuable time with us.

I didn't see cancer on your list of diseases. What is your opinion about the role of Vitamin D and cancer?

I was surprised to see TB on the list. My aunt had it 3 times (in the old days) and spending hours outdoors in the sun was part of the cure. Recently I was reading about the importance of indoor air circulation (with UV lights) in the top of a room for fighting TB. My aunt mentioned that their bedrooms and public rooms all had cross ventilation from windows up high. Perhaps the ventilation indoors and hours outdoors in the sun simply lowered the pathogen levels to that which a body could successfully fight.

Could we say that the amount of Vitamin D a person gets from being out of doors is sufficient? What about those of us in higher latitudes?

.

[palbert]

Re: Cytokine Storm & Vitamin D relationship?

@Florida1: "We are not concerned about the why of the divergence between the WHO and Marshall. We present data and people decide for themselves."

Thanks, Florida1. The politics are interesting, but I try to steer clear of this type of discussion. I believe that everyone is acting in good faith and that there really are different ways to interpret the same observations. Also, I think a lot of the top researchers will readily concede that we need to know more about vitamin D metabolism and its relationship with chronic disease. IMO, the work I am presenting here is a very viable set of explanations and will need to be validated or invalidated.


@Kiwibird: "Then why would you assume that a sick body is making a sensible "decision" by lowering Vitamin D levels."

What we're saying is that even in a state of chronic vitamin D dysregulation, the body will try to do the best that it can under the circumstances, which is to downregulate 25-D. (Thanks for the study on sailors. I hadn't seen that.)


@AlaskaDenise: With regard to vitamin D and cancer, and latitude studies, we have a couple articles that try to answer your questions:

http://mpkb.mp-dev.com/doku.php/home:pathogenesis:vitamind:latitude

http://mpkb.mp-dev.com/doku.php/home:pathogenesis:vitamind:cancer

[St Michael]

Re: Cytokine Storm & Vitamin D relationship?

Just a note, I have no dog in this fight:

Please correct me if I'm wrong, but from a Google search, it appears Paul S. Albert PhD is a follower of Trevor Marshall, Ph.D's theories on Vitamin D.

Those theories are not necessarily widely accepted in the medical field. See the Vitamin D council's entry here:

Cholecalciferol is Cholecalciferol

Dr. Cannell: I understand Dr. Marshall conducted a study and found vitamin D is bad for you. What kind of study did he do? Mary Minneapolis, MN

I have been inundated with letters asking about Professor Marshall's recent "discovery." Some have written that to say they have stopped their vitamin D and are going to avoid the sun in order to begin the "Marshall protocol." The immediate cause of this angst is two publications, a press article in Science Daily about Professor Marshall's "study" (which is no study but simply an opinion) in BioEssays. Dr. Trevor Marshall has two degrees, both in electrical engineering. Before I begin, I want to again remind you that I am a psychiatrist who works at a state mental hospital. In my duty to full disclosure, I must say that I have known a lot of psychiatrists in my life and a few electrical engineers. If I knew nothing else of a disagreement between two people but their professions, I would believe the electrical engineer, not the psychiatrist.

In reading his two articles, Dr. Marshall's main hypotheses are simple:

* Vitamin D from sunlight is different than vitamin D from supplements.
* Vitamin D is immunosuppressive and the low blood levels of vitamin D found in many chronic diseases are the result of the disease and not the cause.
* Taking vitamin D will harm you, that is, vitamin D will make many diseases worse, not better.

If you read his blog, you discover that the essence of the Marshall protocol is: "An angiotensin II receptor blocker medication, Benicar, is taken, and sunlight, bright lights and foods and supplements with vitamin D are diligently avoided. This enables the body's immune system, with the help of small doses of antibiotics, to destroy the intracellular bacteria. It can take approximately one to three years to destroy all the bacteria." That is, Dr. Marshall has his "patients" become very vitamin D deficient.

Again, Dr. Marshall conducted no experiment and published no study. He wrote an essay. He presented no evidence for his first hypothesis (sunlight's vitamin D is different than supplements). From all that we know, cholecalciferol is cholecalciferol, regardless if it is made in the skin or put in the mouth. His second hypothesis is certainly possible and that is why all scientists who do association studies warn readers that they don't know what is causing what. Certainly, when low levels of vitamin D are found in certain disease states, it is possible that the low levels are the result, and not the cause, of the disease. Take patients with severe dementia bedridden in a nursing home. At least some of their low 25(OH)D levels are likely the result of confinement and lack of outdoor activity. However, did dementia cause the low vitamin D levels or did low 25 (OH)D contribute to the dementia? One way to look at that question is to look at early dementia, before the patient is placed in a nursing home. On the first day an older patient walks into a neurology clinic, before being confined to a nursing home, what is the relationship between vitamin D levels and dementia? The answer is clear, the lower your 25(OH)D levels the worse your cognition. Wilkins CH, Sheline YI, Roe CM, Birge SJ, Morris JC. Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults. Am J Geriatr Psychiatry. 2006 Dec;14(12):1032–40. Przybelski RJ, Binkley NC. Is vitamin D important for preserving cognition? A positive correlation of serum 25-hydroxyvitamin D concentration with cognitive function. Arch Biochem Biophys. 2007 Apr 15;460(2):202–5.

These studies suggest that the low 25(OH)D levels are contributing to the dementia but do not prove it. Only a randomized controlled trial will definitively answer the question, a trial that has not been done. So you will have to decide if vitamin D is good for your brain or not. Dr. Marshall seems to be saying demented patients should lower their 25(OH)D levels. Keep in mind, an entire chapter in Feldman's textbook is devoted to the ill effects low vitamin D levels have on brain function. Brachet P, et al. Vitamin D, a neuroactive hormone: from brain development to pathological disorders. In Feldman D., Pike JW, Glorieux FH, eds. Vitamin D. San Diego: Elsevier, 2005.

It is true that in some diseases, high doses of vitamin D may be harmful. For example, in the early part of last century, the AMA specifically excluded pulmonary TB from the list of TB infections that ultraviolet light helps. They did so because many of the early pioneers of solariums reported that acutely high doses of sunlight caused some patients with severe pulmonary TB to bleed to death. Thus, these pioneers developed very conservative sun exposure regimes for pulmonary TB patients in which small areas of the skin were progressively exposed to longer and longer periods of sunlight. Using this method, sunlight helped pulmonary TB, often to the point of a cure. Furthermore, it is well known that sunlight can cause high blood calcium in patients with sarcoidosis. In fact, sarcoidosis is one of several granulomatous diseases with vitamin D hypersensitivity where the body loses its ability to regulate activated vitamin D production, causing hypercalcemia. Cronin CC, et al. Precipitation of hypercalcaemia in sarcoidosis by foreign sun holidays: report of four cases. Postgrad Med J. 1990 Apr;66(774):307–9.

Furthermore, although medical science is not yet convinced, some common autoimmune diseases may have an infectious etiology. I recently spoke at length with a rheumatologist who suffers from swollen and painful joints whenever he sunbathes or takes high doses of vitamin D. As long as he limits his vitamin D input his joints are better. To the extent vitamin D upregulates naturally occurring antibiotics of innate immunity, sunlight or vitamin D supplements may cause the battlefield (the joints) to become hot spots. I know of no evidence this is the case but it is certainly possible.

However, if Dr. Marshall's principal hypothesis is correct, that low vitamin D levels are the result of disease, then he is saying that cancer causes low vitamin D levels, not the other way around. The problem is that Professor Joanne Lappe directly disproved that theory in a randomized controlled trial when she found that baseline vitamin D levels were strong and independent predictors of who would get cancer in the future. The lower your levels, the higher the risk. Furthermore, increasing baseline levels from 31 to 38 ng/ml reduced incident cancers by more than 60% over a four year period. Therefore, advising patients to become vitamin D deficient, as the Marshall protocol clearly does, will cause some patients to die from cancer. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007 Jun;85(6):1586–91.

I will not write again about Dr. Marshall's theories. No one in the vitamin D field takes him seriously. Personally, I admire anyone willing to swim against the tide and raise alternative theories. I have done the same with influenza and autism. However, I agree with the New York Times and Jane Brody's conclusion: "In the end, you will have to decide for yourself how much of this vital nutrient to consume each and every day and how to obtain it." Jane Brody. An Oldie Vies for Nutrient of the Decade. New York Times. 2008 Feb 19. I agree. You will have to decide for yourself.

John Jacob Cannell MD
Executive Director

Do your own research, and come to your own conclusions.

I will not engage in any further debate about Dr. Marshall's theories either.

Full disclosure: I am neither an MD nor a PhD. I am a lowly DPM, a podiatrist.

[palbert]

Re: Cytokine Storm & Vitamin D relationship?

Michael,

No fighting, dog or otherwise.

If you see my original post, you'll see that I have said that Marshall was a co-author. I work closely with Marshall. I think he's largely right. I think the Vitamin D Council is wrong, more or less. But maybe that's obvious?

Believe it or not, I'm not really trying to convince anyone to do anything. I was asked to discuss our explanation of vitamin D metabolism and I'm doing that.

Indeed, decide for yourself! But do try to think about some of the issues I've raised.

Paul