Vitamin D supplementation may help to prevent a range of viral and bacterial infections

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Vitamin D supplementation may help to prevent a range of viral and bacterial infections

New research published today indicates that taking a regular vitamin D supplement will reduce the chance of picking up infections

BBC health report on this research:

http://www.bbc.co.uk/news/health-38988982

Link to previous BBC news item on similar research:
http://www.bbc.co.uk/news/health-36846894 >>>>
Everyone should consider taking vitamin D supplements in autumn and winter, public health advice in England and Wales says.

It comes as a government commissioned report sets the recommended levels at 10 micrograms of the vitamin a day.

But officials are concerned this may not be achievable through diet alone, particularly when sunlight, which helps in vitamin D production, is scarce.

Low vitamin D levels can lead to brittle bones and rickets in children.

Dr Charles Shepherd comments:

We often flag up the fact that people with ME/CFS, especially those who are partially or totally housebound, are at increased risk of developing vitamin D deficiency - mainly due to the lack of exposure to sunlight (which helps with vitamin D production) but this may also be compounded due to lack of foods that are good sources of vitamin D in their diet (i.e. oily fish, eggs, fortified breakfast cereals).

This new advice from Public Health England, which recommends that everyone should consider taking a vitamin D supplement during the autumn and winter months, is therefore very relevant - because vitamin D is essential for good muscle and bone health. So any deficiency of vitamin D in ME/CFS could add to the problems of muscle weakness that is already occurring.

On a personal basis, I will now be following this advice and taking a vitamin D supplement during the autumn and winter months.

Link to the most recent MEA statement on vitamin D and ME/CFS and our June 2016 MEA website poll on the subject:

http://www.meassociation.org.uk/201...-in-this-months-mea-website-poll-1-june-2016/

All aspects of vitamin D, and vitamin D deficiency, are covered in the MEA information leaflet on vitamin D:
http://www.meassociation.org.uk/shop/management-leaflets/vitamin-d/

Summary of key points relating to the vitamin D (25-hydroxyvitamin D) blood test:
The National Osteoporosis society (NOS) guidelines (UK, 2013) and the Institute of Medicine (US) classify vitamin D results as follows:

  • 25-hydroxyvitamin D of less than 30 nmol/L is deficient
  • 25-hydroxyvitamin D of 30-50 nmol/L may be inadequate in some people
  • 25-hydroxyvitamin D of greater than 50 nmol/L is sufficient for almost the whole population.
Low blood levels of 25-hydroxyvitamin D may mean that you are not getting enough exposure to sunlight or enough vitamin D in your food to meet your body's demand or that there is a problem with its absorption from the intestines. Occasionally, drugs used to treat seizures, particularly phenytoin (epanutin), can interfere with the liver's production of 25-hydroxyvitamin D.

High levels of 25- hydroxyvitamin D usually reflect excess supplementation from vitamin pills or other nutritional supplements.

More info on the vitamin D blood test: http://labtestsonline.org.uk/understanding/analytes/vitamin-d/tab/glance/

Summary of research into vitamin D and ME/CFS from the MEA purple book (2016 edition):

Consider vitamin D deficiency in adults with restrictive diets and lack of access to sunlight. A retrospective study of serum 25-OH (hydroxy) vitamin D levels in 221 ME/CFS patients found moderate to severe suboptimal levels, with a mean level of 44.4nmol/l (Berkovitz et al 2009).

Vitamin D deficiency often goes unrecognised and can cause bone or muscle pain and muscle weakness. It can co-exist with ME/CFS.

Levels < 25nmol/ml may be associated with symptoms.

NB: Low serum calcium and phosphate and an elevated alkaline phosphatase are consistent with osteomalacia.


Dr Charles Shepherd
Hon Medical Adviser, MEA
 

aaron_c

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I haven't actually posted about this in this much detail before, and it seemed like a good place to do so. In my experience supplementing with Vitamin D can be problematic for many people with ME/CFS, and I have some ideas about the whole thing:

Possible Answers to Two Questions I Have Had:
1. Why Does Vitamin D Make So Many Of Us Tired (And Can Anything Be Done)?
2. Why Does Vitamin D Help With My "Ammonia" Symptoms?



Many of us with ME/CFS get quite exhausted from oral vitamin D (see this thread). Personally, I suspect this is from an interaction between vitamin D and TGF-Beta, which "potently induce 5-lipoxygenase," at least in myeloid cells [1]. Many people with CFS have high TGF-Beta [2]. I tested this theory on myself by taking the 5-LO inhibitor acetyl-11-keto-beta-boswellic acid (AKBA), which proved successful in eliminating the vitamin d-induced fatigue--although over time it failed to prevent other side effects and I had to abandon oral vitamin D3 [3]. Alternately, @nandixon had a slightly different theory for why vitamin D makes us tired.

Whatever the cause, using a UV-B lamp gives me most of the benefits of oral vitamin D without triggering any of the negative side effects. The main benefit I get from vitamin D is a lessening/elimination of so-called "ammonia" symptoms, which I believe to essentially boil down to BH4 deficiency caused by NOS uncoupling caused by an increase in asymmetric dimethyl arginine (ADMA) relative to arginine [4]. Vitamin D deficiency increases production of TNF-alpha by white blood cells exposed to lipopolysaccharide [5], and TNF-alpha is known to decrease the function of DDAH, which breaks down ADMA [6]. Low vitamin D has also been correlated with high ADMA [7]. So it seems likely to me that, at least for some of us, vitamin D will decrease ADMA and thus increase BH4.

To some degree the particulars of the science don't really matter. The essential story is that I feel unwell (in a very particular way) within a day or two of skipping out on my UV-B lamp, and that this particular unwell feeling can also be eliminated by oral vitamin D (albeit with some severe side effects). So I can tell that the UV-B lamp is doing something, and I can attest that whatever it does it appears to share many functions with oral vitamin D3. And it does this without the severe fatigue and other negative side effects I get from taking oral vitamin D.

So what is the difference between oral vitamin D and vitamin D made in our own skin? I don't know for sure, but the most promising link I have found so far comes from the controversial researcher Stephanie Seneff, who says that vitamin D produced in the skin is in sulfated form, which gives it somewhat different biochemistry from the vitamin D3 found in, for instance, cod oil [8]. She also claims that sunlight stimulates the skin to produce cholesterol sulfate, although I'm not sure what, if any, role that plays here [8].

In summary: I hope that some people with ME/CFS who have low vitamin D and/or "ammonia" symptoms, and particularly those who respond poorly to oral vitamin D will consider trying a UV-B lamp as a possible alternative. And if people do try a UV-B lamp, I hope they will post feedback either here or on the Vitamin D thread I linked above, regardless of whether the feedback is pro or con.

And thank you in advance, @charles shepherd , for letting me threadjack to the degree I have. Perhaps colored by my own experience with vitamin D, it seems to me an important enough point to bring up in the context of recommendations being made to the ME/CFS community.

Best Wishes,

Aaron C


Sources:

  1. Sorg BL, Klan N, Seuter S, Dishart D, Rådmark O, et al.Analysis of the 5-lipoxygenase promoter and characterization of a vitamin D receptor binding site.Biochim Biophys Acta2006;1761: 686–697.[PubMed]
  2. Bennett AL, Chao CC, Hu S, Buchwald D, Fagioli LR, Schur PH. Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome.J Clin Immunol.1997;17:160–166. doi: 10.1023/A:1027330616073.[PubMed][Cross Ref]
  3. Sailer ER, Subramanian LR, Rall B, Hoernlein RF, Ammon HP, Safayhi H. Acetyl 11-keto-b-boswellic acid (AKBA): Structure requirements for binding and 5-lipoxygenase inhibitory activity. Br J Pharmacol. 1996;117(4):615–618. doi: 10.1111/j.1476-5381.1996.tb15235.x. [PMC free article] [PubMed] [Cross Ref]
  4. Schwedhelm E, Boger RH. The role of asymmetric and symmetric dimethylarginines in renal disease.Nat Rev Nephrol.2011;7(5):275–285. doi: 10.1038/nrneph.2011.31. Link
  5. Yong Zhang, Donald Y. M. Leung, Brittany N. Richers, Yusen Liu, Linda K. Remigio, David W. Riches, And Elena Goleva.Vitamin D Inhibits Monocyte/Macrophage Proinflammatory Cytokine Production by Targeting MAPK Phosphatase-1.The Journal of Immunology, March 1, 2012 DOI:10.4049/%u200Bjimmunol.1102412. [or see the summary here]
  6. Ito A, Tsao PS, Adimoolam S, Kimoto M, Ogawa T, Cooke JP. Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase.Circulation.1999;99:3092–5.[PubMed]
  7. Ngo DT, Sverdlov AL, McNeil JJ, Horowitz D. Does vitamin D modulate asymmetric dimethylarginine and C-reactive protein concentrations?Am J Med.2010;123:335–41.[PubMed]
  8. http://articles.mercola.com/sites/articles/archive/2011/09/17/stephanie-seneff-on-sulfur.aspx (Apologies on this last link...I hope in the future to be well enough to really look into this. For now, I will take Dr. Seneff's assertion as a fascinating possibility.)
 
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Vitamin D has been a weird one for me personally. At times t seems to really help my mood and pain levels, others it sort of wires me. It seems as long as I keep the dose reasonable and have a lot of magnesium it treats me pretty well. Of course my levels when measured are fine so I sort of just take it by feel and doing it this way seems to give me a boost.
 
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I wonder how many people who are sensitive to Vitamin D are also sensitive to calcium. I bet there is a subset of people who are already high in the active form. I think KDM says this means inflammation. I think vitamin D ingestion worsens neuroinflammation by increasing Calcium absorption thereby increasing intrcelluar calcium in the brain which leads to Ca2+ signanling excitoxicity. Simultaneously, a CFS brain that also has to deal with existing microglial activation, Excessive oxidative stress, low Glutathione, and mitochondrial dysfunction will further damage and make one very sensitive to vitamin D supplementation.

In my case, supplementing with vitamin D causes me the same symptoms as supplementing with Calcium or ingesting any foods high in calcium. It causes an increase in my excitotoxic symptoms- ear ringing(ototoxicity), anxious, racing mind, panic attacks, sizzling in my brain with a stabbing sensation. I cannot even tolerate a drop which is 100 mg.
 

nandixon

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Alternately, @nandixon had aslightly different theory for why vitamin D makes us tired.
That idea I suggested previously probably isn't correct now. It's likely too far downstream.

I believe now that the problem may be that in those of us who, for whatever reason, don't have properly regulated levels of 1,25-dihydroxyvitamin D3 (calcitriol), that that causes further inhibition of the Akt/mTOR (mTORC1) pathway, which I believe the recent Fluge & Mella study has shown to be under-activated in ME/CFS. (See my signature and other posts in the thread linked to.)

Calcitriol inhibits mTOR in multiple different ways, and so is going to be a problem when it goes too high in the subset of ME/CFS people who have that problem. (A significant percentage of the normal healthy population also has a tendency for high calcitriol levels, around 15% if I remember correctly, but they don't notice it, except for a tendency to develop kidney stones, or unless they take really large doses of vitamin D3.)
 
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kangaSue

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I don't have ME/CFS but I don't tolerate oral vitamin D because of chronic GI dysfunction but had to do something about it recently with being diagnosed with Osteoporosis so bit the bullet and tried this https://www.mja.com.au/journal/2005...-megadose-cholecalciferol-treatment-vitamin-d an injection of a megadose of Vit D which I had no issue with at all.

I went that route because I saw this study http://www.healio.com/rheumatology/...loskeletal-pain-in-patients-with-fibromyalgia which found a smaller megadose of Vit D as cholecalciferol could help with fatigue and pain in Fibromyalgia too
 

xena

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I haven't actually posted about this in this much detail before, and it seemed like a good place to do so. In my experience supplementing with Vitamin D can be problematic for many people with ME/CFS, and I have some ideas about the whole thing:

Possible Answers to Two Questions I Have Had:
1. Why Does Vitamin D Make So Many Of Us Tired (And Can Anything Be Done)?
2. Why Does Vitamin D Help With My "Ammonia" Symptoms?



Many of us with ME/CFS get quite exhausted from oral vitamin D (see this thread). Personally, I suspect this is from an interaction between vitamin D and TGF-Beta, which "potently induce 5-lipoxygenase," at least in myeloid cells [1]. Many people with CFS have high TGF-Beta [2]. I tested this theory on myself by taking the 5-LO inhibitor acetyl-11-keto-beta-boswellic acid (AKBA), which proved successful in eliminating the vitamin d-induced fatigue--although over time it failed to prevent other side effects and I had to abandon oral vitamin D3 [3]. Alternately, @nandixon had a slightly different theory for why vitamin D makes us tired.

Whatever the cause, using a UV-B lamp gives me most of the benefits of oral vitamin D without triggering any of the negative side effects. The main benefit I get from vitamin D is a lessening/elimination of so-called "ammonia" symptoms, which I believe to essentially boil down to BH4 deficiency caused by NOS uncoupling caused by an increase in asymmetric dimethyl arginine (ADMA) relative to arginine [4]. Vitamin D deficiency increases production of TNF-alpha by white blood cells exposed to lipopolysaccharide [5], and TNF-alpha is known to decrease the function of DDAH, which breaks down ADMA [6]. Low vitamin D has also been correlated with high ADMA [7]. So it seems likely to me that, at least for some of us, vitamin D will decrease ADMA and thus increase BH4.

To some degree the particulars of the science don't really matter. The essential story is that I feel unwell (in a very particular way) within a day or two of skipping out on my UV-B lamp, and that this particular unwell feeling can also be eliminated by oral vitamin D (albeit with some severe side effects). So I can tell that the UV-B lamp is doing something, and I can attest that whatever it does it appears to share many functions with oral vitamin D3. And it does this without the severe fatigue and other negative side effects I get from taking oral vitamin D.

So what is the difference between oral vitamin D and vitamin D made in our own skin? I don't know for sure, but the most promising link I have found so far comes from the controversial researcher Stephanie Seneff, who says that vitamin D produced in the skin is in sulfated form, which gives it somewhat different biochemistry from the vitamin D3 found in, for instance, cod oil [8]. She also claims that sunlight stimulates the skin to produce cholesterol sulfate, although I'm not sure what, if any, role that plays here [8].

In summary: I hope that some people with ME/CFS who have low vitamin D and/or "ammonia" symptoms, and particularly those who respond poorly to oral vitamin D will consider trying a UV-B lamp as a possible alternative. And if people do try a UV-B lamp, I hope they will post feedback either here or on the Vitamin D thread I linked above, regardless of whether the feedback is pro or con.

And thank you in advance, @charles shepherd , for letting me threadjack to the degree I have. Perhaps colored by my own experience with vitamin D, it seems to me an important enough point to bring up in the context of recommendations being made to the ME/CFS community.

Best Wishes,

Aaron C


Sources:

  1. Sorg BL, Klan N, Seuter S, Dishart D, Rådmark O, et al.Analysis of the 5-lipoxygenase promoter and characterization of a vitamin D receptor binding site.Biochim Biophys Acta2006;1761: 686–697.[PubMed]
  2. Bennett AL, Chao CC, Hu S, Buchwald D, Fagioli LR, Schur PH. Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome.J Clin Immunol.1997;17:160–166. doi: 10.1023/A:1027330616073.[PubMed][Cross Ref]
  3. Sailer ER, Subramanian LR, Rall B, Hoernlein RF, Ammon HP, Safayhi H. Acetyl 11-keto-b-boswellic acid (AKBA): Structure requirements for binding and 5-lipoxygenase inhibitory activity. Br J Pharmacol. 1996;117(4):615–618. doi: 10.1111/j.1476-5381.1996.tb15235.x. [PMC free article] [PubMed] [Cross Ref]
  4. Schwedhelm E, Boger RH. The role of asymmetric and symmetric dimethylarginines in renal disease.Nat Rev Nephrol.2011;7(5):275–285. doi: 10.1038/nrneph.2011.31. Link
  5. Yong Zhang, Donald Y. M. Leung, Brittany N. Richers, Yusen Liu, Linda K. Remigio, David W. Riches, And Elena Goleva.Vitamin D Inhibits Monocyte/Macrophage Proinflammatory Cytokine Production by Targeting MAPK Phosphatase-1.The Journal of Immunology, March 1, 2012 DOI:10.4049/%u200Bjimmunol.1102412. [or see the summary here]
  6. Ito A, Tsao PS, Adimoolam S, Kimoto M, Ogawa T, Cooke JP. Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase.Circulation.1999;99:3092–5.[PubMed]
  7. Ngo DT, Sverdlov AL, McNeil JJ, Horowitz D. Does vitamin D modulate asymmetric dimethylarginine and C-reactive protein concentrations?Am J Med.2010;123:335–41.[PubMed]
  8. http://articles.mercola.com/sites/articles/archive/2011/09/17/stephanie-seneff-on-sulfur.aspx (Apologies on this last link...I hope in the future to be well enough to really look into this. For now, I will take Dr. Seneff's assertion as a fascinating possibility.)
Wow ok so that's very interesting
CBS is actually downregulated by nitric oxide which is produced when uv hits the skin
Could that be related? I don't know or under what the NOS enzyme does in relation to any of this detox wise but maybe it will make sense to you. Very exciting to hear that uv helps your ammonia symptoms.
Check this out :

https://m.facebook.com/drjackkruse/posts/1103962676334752?locale2=hi_IN

https://forum.jackkruse.com/index.php?threads/nitric-oxide-key-skin-molecule-with-uv.17214/

Also, see Yasko on the effect of light and vitamin D on bh4 levels at 8:40 in this video

 

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aaron_c

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I didn't realize Yasko knew of a link between sunlight and BH4...huh. The papers she show are behind paywalls, but I hadn't seen them before. Thanks!

I'm not sure how much NO in the skin would help with CBS problems, even assuming that CBS overactivity is problematic (I think it likely is not). If you look at biogps, you'll see that CBS is mostly expressed in the liver. NO exerts its effect locally, I think because it doesn't get far without being oxidized. To get an idea of how local this is, think of how local the vasodilation is for an erection. So most of the NO produced in the skin won't make it to the liver. Maybe it would have an effect on the little bit of CBS that exists outside of the liver...

On the other hand, the research on NO as a possible mechanism for regulating CBS is fascinating. I've heard arguments both that we have too much NO (Martin Pall) and that we have not enough. I think this article discusses the confusion.

If the problem is that we have insufficient NO then I suppose excessive CBS activity is still on the table. Although to some degree this would make sense as a feedback mechanism, since increased CBS activity could lead to increased glutathione production, which would quench superoxide, which otherwise would combine with NO to form peroxynitrite (ONOO). So increased glutathione should mean a little more NO and a little less ONOO, which should normally form a self-correcting feedback loop.

The Jack Kruse stuff is interesting...and I don't understand it all. Unfortunately, something about his writing makes me skeptical. Again, because I can't 100% follow I can't point out any one place he is wrong. But he at least seems to use language in an imprecise way, like when he says "What creates electron spin? MITOCHONDRIA." Just by googling I see that electron spin is an intrinsic property of electrons, so I think that what he said is like saying "What creates water temperature? THE FURNACE." (No it doesn't, a furnace creates heat.)
 
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Tunguska

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@aaron_c I'm similar to you in that oral D is useless while sunlight is very helpful sometimes was essential for things to work (I still have to get a UVB light, thanks for reminding me! I used other lights for awhile to small effect).

But I was/am very sensitive to NO and increased NO got to be clearly the major effect I got from sunlight - a positive effect. Makes it hard to discern anything else.

It doesn't stop at Jack Kruse, there are more ideas out there and you start to wonder if Vitamin D even matters (I know, it does).
 

Tunguska

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Can you describe how you can tell when you have low and high NO?
Increased NO is/was, in short: Increased blood flow, relaxation of muscles, joint relief, and (this no longer happens reliably) lessening of brain fog, mental clarity.

The same effect (for a given point in time) as GPLC, progesterone, arginine, etc.
 

aaron_c

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If sunlight is producing NO in the way I described in the link above (vitamin d reducing ADMA levels so NOS is more often coupled) then one of the benefits would be increased NO and decreased ONOO, and that should occur throughout the body.

So maybe these explanations aren't fundamentally in conflict.
 

serg1942

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Great thread! I just want to add my 2 cents... I am finishing a comprehensive review on vitamin D and inflammatory conditions. I just wanted to make sense of all the contradictory evidence I was finding. I will be posting my article when I finish it, but in the meantime, just a word of advice, as I don't think vit D supplementation is of any benefit for ME/CFS. Basically, it suppresses most parts of the immune system when supplemented: the whole acquired response, the innate response (NKs, TLRs...), the antigen presentation process...It has shown to be as powerful as any glucocorticoid... So, yes, definitively it can relieve some symptoms, but in the long run I think it can only be harmful... Another thing is to take a bit of sun or some UV-B... This would be considered as "phsysiological" supplementation, which I think might be beneficial...

Best,
Sergio

P.S. Here are just a few paragraph of the review I'm working on. I hope it's helpful.:
*********************************
The general recognized effect of VD1,25 is to enhance the innate immune system by enhancing monocyte phagocytosis and autophagy, and to inhibit the adaptative response by decreasing MHC and co-stimulatory molecules expression, leading to a reduced ability to activate T cells. In this vein, vitamin D has shown to block the formation of Th1 cytokines, specially IFN-γ, and to promote a Th2-mediated-immune response by haltering the synthesis of IFN-γ and promoting IL-4 production. Furthermore, VD1,25 also down-regulates the Th17-mediated responses, probably by inhibiting the production of IL-6 and IL-23.

In consequence, the effect of vitamin D on different immune cells is large. In accordance with its capacity to inhibit the T cell proliferation and effectiveness, VD1,25 has demonstrated to induce Foxp3+ Treg cells differentiation. Furthermore, VD1,25 promotes the M2-phenotype of macrophages over the “inflammatory” or M1-phenotype. 5,6,https://forums.phoenixrising.me/file:///E:/drop/Dropbox/S/A%20MEDICINA/bioq.med/mis%20art%C3%ADculos/Vitamin%20D/Vitamin%20D,%20friend%20or%20foe.docx#_edn1 As for the Dendritic Cells (DC), the effect that vitamin D exerts on them is quite extensive. As demonstrated by Piemonti et al, [ii] VD1,25 interferes with differentiation of monocytes into DCs in culture. The DC formed under the influence of this hormone show enhanced antigen (Ag) uptake capacity and inhibited immunostimulatory capacity. Their capability to present Ags to T cells seems to be impaired as well, showing an augmented endocytic activity. Accordingly, Piemonti et al results further show that DC treated with VD1,25, when exposed to LPS, induce a state of non-alloantigen-restricted hyporesponsivity in T cells, meaning that T cells were induced into the anergic state by DCs obtained from either the same donor or from an unrelated one. This experiment also showed reduced IL-12 production, a cytokine involved in the differentiation of naive T cells into Th1 cells, [iii] after exposure to CD40L, LPS, or TNF-α. Piemonti et al conclude: “The inhibitory effect of 1α,25-(OH)2D3 on DC maturation and differentiation is very similar to that of IL-10, an anti-inflammatory cytokine, and to that of glucocorticoids [emphasis added](…) because DC have the unique property to activate naive T cells and are required for the induction of a primary response, the suppression of DC function may very efficiently control the specific immune response”. (Piemonti et al, 2000). Aditionally, and following the same pattern of immunosuppression, VD1,25 has shown to significantly reduce abnormal PBMC responsiveness to multiple sclerosis-associated antigens,and to downregulate T cell-driven IgG production. [iv] Along the same line, VD1,25 downregulates the expression of many proinflammatory cytokines, such as IL-1, IL-6, IL-8, and TNF-α, in many cell types. [v]


https://forums.phoenixrising.me/file:///E:/drop/Dropbox/S/A%20MEDICINA/bioq.med/mis%20art%C3%ADculos/Vitamin%20D/Vitamin%20D,%20friend%20or%20foe.docx#_ednref1 Ota, K., Dambaeva, S., Kim, M., et al. 1,25-Dihydroxy-vitamin D3 regulates NK-cell cytotoxicity, cytokine secretion, and degranulation in women with recurrent pregnancy losses. European Journal Of Immunology. 2015; 45(11), 3188-3199.

[ii] Lorenzo Piemonti, et al. Vitamin D3 Affects Differentiation, Maturation, and Function of Human Monocyte-Derived Dendritic Cells. The Journal of Immunology May 1, 2000, 164 (9) 4443-4451.

[iii] Wagner, M., Poeck, H., Jahrsdoerfer, B., et al. IL-12p70-Dependent Th1 Induction by Human B Cells Requires Combined Activation with CD40 Ligand and CpG DNA. The Journal Of Immunology. 2004;172(2), 954-963.

[iv] Sun J. Vitamin D and mucosal immune function. Current opinion in gastroenterology. 2010;26(6):591-595.

[v] Kimball S, Vieth R, Dosch H-M, et al. Cholecalciferol Plus Calcium Suppresses Abnormal PBMC Reactivity in Patients with Multiple Sclerosis. The Journal of Clinical Endocrinology and Metabolism. 2011;96(9):2826-2834.


*******************
2.4 Comparison between VD1,25 and dexamethasone:

Unger et al. trial from 2009 https://forums.phoenixrising.me/file:///E:/drop/Dropbox/S/A%20MEDICINA/bioq.med/mis%20art%C3%ADculos/Vitamin%20D/Vitamin%20D,%20friend%20or%20foe.docx#_edn1, compared the anti-inflammatory properties of VD1,25 and dexamethasone. They found that when monocytes are treated with either VD1,25 or dexamethasone, the DCs formed correlate with stable and semi-mature phenotypes with intermediate levels of co-stimulatory and MHC class II molecules, what supports the previous findings of VD1,25 impairing the Ag-presentation-capacity of DCs. Furthermore, the authors found that both VD1,25 and dexamethasone possess the capacity to convert CD4+T cells into IL-10-secreting Tr1-like Treg-cells, an indication of a potent suppressive effect of VD1,25 on T-cells proliferation; however, only Treg induced by VD1,25-treated-DC exhibited antigen specificity. Additionally, the DCs treated with both VD1,25 and dexamethasone, secreted less IL-12p70, but the amount of IL-10 was unchanged, what demostrates the Th1-inhibition properties of both substances compared in this study.

From Unger et al results, it is possible to observe that the potency of VD1,25 and that of dexamethasone in suppressing T cell proliferation is pretty similar (75% and 60% of suppression respectively). Delving deeper into this comparison, the authors note that both VD1,25 and dexamethasone show anti-inflammatory properties achieved also by means of gene expression. Finally, the authors mimicked in vivo DC activation by activated T cells using CD40 triggering, and found similar results. In conclusion, it seems that the anti-inflammatory properties and potency of VD1,25 and dexamethasone are quite similar. In agreement with this, VD1,25 is considered to be the most potent steroid hormone in the human body. 6These assertions are in line with the conclusion quoted above from Piemonti and collegues’ study, stating that the inhibitory effect of VD1,25 on DC is very similar to the effect of glucocorticoids. 11


https://forums.phoenixrising.me/file:///E:/drop/Dropbox/S/A%20MEDICINA/bioq.med/mis%20art%C3%ADculos/Vitamin%20D/Vitamin%20D,%20friend%20or%20foe.docx#_ednref1 Unger, W., Laban, S., Kleijwegt, F., van der Slik, A., & Roep, B. Induction of Treg by monocyte-derived DC modulated by vitamin D3or dexamethasone: Differential role for PD-L1. European Journal Of Immunology. 2009;39(11), 3147-3159.