DISCLAIMER: I have no official credentials (i.e. university degrees in science) that would confer on me the recognized scientific expertise to elaborate on and interpret scientific articles. It follows that any conclusions I might have reached do not have validity unless confirmed by someone with appropriate scientific expertise. Lastly, as English is not my first language and the current text has not been reviewed by a qualified translator, I take no responsibility for any
misunderstandings or misinterpretations that might arise from my grammatical errors. This text must therefore be viewed as a layman’s interpretation of the sources that have been noted.
Post's author background:
I'm an industrial engineer and a 5th-year medical student. I suffer from CFS and from chronic Lyme disease.
Personal notes before reading this post:
- I am sorry for writing the subject of the post in capital letters. I just copied and pasted the title from my whole article, and didn't even notice it was in capitals letters. I understand this might come somewhat too strong for some people, so I just changed it. Again, I apologized to those who have felt offended in any way.
- As I have been suggested, I have written down the disclaimer which was in my article, on top of my original post, together with my credentials, so you don't have any doubt about the validity of the article.
- The article I wrote is very well referenced, with cites properly placed from 58 scientific papers (my background as engineer allows me to know how to do this), which are listed at the end of the article. You can perfectly distinguish what comes from a given paper from those conclusions I reached on my own (which is not much--most things are paraphrased and properly referenced).
- I have been told that my assertions are too aggressive. I apologize if they came up that way. I just manage in English, so please understand that it is very difficult for me to grasp these nuances... Again, I apologize for this.
- However, I guess I am allowed to write down conclusions made by scientific papers. Thus, when I say that vitamin D is an immune suppressor as powerful as a glucocorticoid, it is because it has been shown in several studies, which I properly quote in my article. Likewise, when I say that vitamin D might be dangerous, again, I am paraphrasing some authors. And when I state that I think that vitamin D supplementation could be counter-productive for chronic inflammatory diseases, I am making a conclusion based on tents of papers which advice just that. If this is worrisome, well, it actually is, in my humble and layman's opinion, and in some expert's opinions as well, which are properly cited in my text. I have just made a thorough scientific review, and highlighted some of the conclusions reached in some papers. Of course, this is just one of the views, as I extensively show in my article; Many physicians do defend vitamin D supplementation.
- Now I do hope I have made things clearer. It is up to us to draw conclusions from the available literature, own experiences, etc. etc.
- Please let me know if I still need to change something. I'll do it gladly. But I won't sugar-coat what some compelling evidence has shown. It would not do any good to anybody, in my opinion, and I guess I am actually allowed to have an opinion on my own, which now I hope it is clear it is just a layman's opinion.
Hi everybody,
I have finally finished a comprehensive review on vitamin D and chronic diseases. I embarked in such a big task because the literature was really confusing and contradictory on whether it is advisable to take vitamin D, or whether it could be even dangerous. This is a very important issue for me because I am still placing my hopes on LDI, a treatment that has almost cured my mom (something seems to be impeding that she gets 100% asymptomatic, but she is most of the days), and that has given to me a very significant but transitory improvements, several times in the past. Thing is that LDI is supposed to work when taking very high doses of vitamin D, and therefore I have been supplementing with this hormone for a long time, while racking my brain trying to figure out a reason for the therapy to stop working on me and others over time… Well, interestingly and much to my surprise, I recently came across with some studies showing the powerful immune-suppressive effects of vitamin D (as powerful as any glucocorticoid), and even most worrisome, I read some studies showing that it inhibits the antigen-presentation process of dendritic cells, which lies at the very heart of the LDI mechanism. Actually, given that vitamin D is fat-soluble, it would make sense that it would accumulate in the body over time and that at one point it could prevent the therapy from working, especially taking into account that its immune-suppressive properties seem to be dose-dependent.
Well, for this reason I have performed a thorough review on vitamin D on chronic inflammatory diseases (such as ME/CFS), that maybe can be also helpful to some of you guys, as I think, after having done this review, that vitamin D supplementation could actually inhibit many therapies we follow.
Below is the summary of the article. attached is full text.
I hope it is helpful,
Best!
Sergio
************************
ABSTRACT
Low levels of the pre-hormone 25-hydroxyvitamin D (VD25) are normally shown in many chronic inflammatory diseases, and many studies show symptomatic improvements, lower rates of autoimmune diseases and fewer inflammatory markers, from taking vitamin D supplements. This has led many physicians and governments to argue that low levels of VD25 lie at the core of the pathogeneses of many conditions, and therefore vitamin supplementation is broadly recommended. However, some physicians and researchers defend the so called “alternate hypothesis”, which describes the low levels of vitamin D as a consequence of the chronic inflammation, instead of the cause. If the proponents of the alternate theory were right, vitamin D supplementation could be really dangerous; therefore, it is of imperative importance to review the available evidence and draw a solid conclusion on the matter.
One of the most important functions of vitamin D is exerted on the immune system. In this regard, when certain Toll-Like-Receptors (TLR) are activated, mainly on monocytes and macrophages, the circulating VD25 is converted into the active form 1,25dihydroxycholecalciferol (VD1,25) by the cells, which in turn induces the expression of antimicrobial peptides (AMPs) by binding to the nuclear vitamin D receptor (VDR). These peptides (mainly cathelicidins and beta defensins) constitute a major component of the innate immune system, showing activity against bacteria, fungi and viruses.
While the most accepted effect of vitamin D on the immune system is to enhance the innate immune response and to inhibit the acquired immunity, in vitro essays as well as interventional studies show contradictory results. In this vein, VD1,25 has demonstrated to block the conversion of Th1- and Th17- cytokines while promoting the Th2-immune response and the formation of Treg-cells. VD1,25 has also shown to inhibit the maturation and proliferation of dendritic cells (DC), to halter the antigen presentation capacity of DC and other antigen-presenting-cells, and to promote the anti-inflammatory and tolerogenic phenotypes of macrophages and DC. Furthermore, it has shown to induce hyporesponsivity in T cells and in peripheral blood mononuclear cells (PBMC), and to inhibit antibody secretion and autoantibody production by B-lymphocytes. Moreover, and in respect to the innate immunity, it has been reported that VD1,25 inhibits TLR2, TL4 and TLR9 as well as NK-cells.
There is a significant paradox, in that vitamin D is necessary for an efficient innate response against numerous intracelular pathogens, but at the same time, it has shown to impair both the innate and the Th1-mediated immune responses. In this vein, some of these discrepancies shown in the literature could be explained by the different doses of VD1,25 or VD25 used in the experiments. Thus, the studies using supraphysiological doses are those which show the most immunosuppressant effects of VD1,25, while some studies using physiological doses report, for example, that VD1,25 does not impede the Th1-mediated response or that the TLR and NK-cells are not inhibited by VD1,25 when lower doses are used. In any way, it seems clear after reviewing some of the literature, that the high VD1,25 serum levels found in patients with many chronic inflammatory and autoimmune conditions, can actually suppress significantly the immune system. In this regard, the anti-inflammatory properties and potency of VD1,25
(in considered physiological doses) and dexamethasone have been shown to be quite similar. Likewise, the inhibitory effect of VD1,25 on DC was shown to be very similar to the effect of glucocorticoids. In anyway, the effects of vitamin D supplementation observed in interventional studies are very useful in elucidating the effects of vitamin D on the immune system. In this regard, vitamin D supplementation in patients with multiple sclerosis, confirmed the promotion of tolerogenic DC, which in turn induced regulatory T cells and produced a shift toward T-helper-type 2 response. In this vein, PBMC responsiveness to disease-associated antigens was significantly reduced, while the signs and symptoms of the disease improved. Likewise, supplementation of vitamin D in patients with cystic fibrosis showed similar results.
Finally, at the end of this article, the “alternate theory” is described in detailed. This model proposes that, in chronic inflammatory and autoimmune diseases, intracellular microbes invade nucleated cells, inhibiting the VDR. This leads to high levels of VD1,25, low levels of VD25 and low-grade chronic inflammation and autoimmune processes produced by cross-reactivity, what would explain the symptoms of these diseases. When these conditions take place, AMPs cannot be properly expressed, what renders the immune system unable to eradicate the perpetuated infections. Thus, in this proposed-disease-model, extra vitamin D supplementation would be really harmful, as it can displace the VD1,25 from the VDR, blocking this receptor even more. In addition, vitamin D supplementation can further hamper AMPs production, what inhibits the innate response towards the intracellular pathogens even further.
If the alternate theory is accurate, the vitamin D supplementation in chronic inflammatory and
autoimmune diseases can be detrimental and dangerous, as it would allow the intracellular pathogens to spread, and the chronic situation would become even worse. Paradoxically, this can lead to transient symptomatic relief, in a way similar to that of many anti-inflammatory drugs.
Is the alternate theory supported by evidence? After a thorough review, we could conclude that it is. In this respect, low levels of VD25 are clearly associated with a wide variety of conditions; similarly, in many of these diseases the VD1,25 have been found to be elevated. In a similar vein, various pathogens have shown to down-regulate the VDR (including mycobacterium tuberculosis, mycobacterium leprae, aspergillus fumigatus, Epstein–Barr virus, HIV and borrelia burgdorferi). Finally, low levels of AMPs have been reported in some autoimmune conditions.
In summary, after an exhaustive review of the literature, we can conclude that low levels of VD25 are possibly due to the effects of chronic inflammation, and not the other way around. In this respect, and given the fact that the so called “alternate theory” seems to be well supported by the literature, it seems advisable to be very careful when it comes to vitamin D supplementation, especially in those with chronic inflammatory diseases.
misunderstandings or misinterpretations that might arise from my grammatical errors. This text must therefore be viewed as a layman’s interpretation of the sources that have been noted.
Post's author background:
I'm an industrial engineer and a 5th-year medical student. I suffer from CFS and from chronic Lyme disease.
Personal notes before reading this post:
- I am sorry for writing the subject of the post in capital letters. I just copied and pasted the title from my whole article, and didn't even notice it was in capitals letters. I understand this might come somewhat too strong for some people, so I just changed it. Again, I apologized to those who have felt offended in any way.
- As I have been suggested, I have written down the disclaimer which was in my article, on top of my original post, together with my credentials, so you don't have any doubt about the validity of the article.
- The article I wrote is very well referenced, with cites properly placed from 58 scientific papers (my background as engineer allows me to know how to do this), which are listed at the end of the article. You can perfectly distinguish what comes from a given paper from those conclusions I reached on my own (which is not much--most things are paraphrased and properly referenced).
- I have been told that my assertions are too aggressive. I apologize if they came up that way. I just manage in English, so please understand that it is very difficult for me to grasp these nuances... Again, I apologize for this.
- However, I guess I am allowed to write down conclusions made by scientific papers. Thus, when I say that vitamin D is an immune suppressor as powerful as a glucocorticoid, it is because it has been shown in several studies, which I properly quote in my article. Likewise, when I say that vitamin D might be dangerous, again, I am paraphrasing some authors. And when I state that I think that vitamin D supplementation could be counter-productive for chronic inflammatory diseases, I am making a conclusion based on tents of papers which advice just that. If this is worrisome, well, it actually is, in my humble and layman's opinion, and in some expert's opinions as well, which are properly cited in my text. I have just made a thorough scientific review, and highlighted some of the conclusions reached in some papers. Of course, this is just one of the views, as I extensively show in my article; Many physicians do defend vitamin D supplementation.
- Now I do hope I have made things clearer. It is up to us to draw conclusions from the available literature, own experiences, etc. etc.
- Please let me know if I still need to change something. I'll do it gladly. But I won't sugar-coat what some compelling evidence has shown. It would not do any good to anybody, in my opinion, and I guess I am actually allowed to have an opinion on my own, which now I hope it is clear it is just a layman's opinion.
Hi everybody,
I have finally finished a comprehensive review on vitamin D and chronic diseases. I embarked in such a big task because the literature was really confusing and contradictory on whether it is advisable to take vitamin D, or whether it could be even dangerous. This is a very important issue for me because I am still placing my hopes on LDI, a treatment that has almost cured my mom (something seems to be impeding that she gets 100% asymptomatic, but she is most of the days), and that has given to me a very significant but transitory improvements, several times in the past. Thing is that LDI is supposed to work when taking very high doses of vitamin D, and therefore I have been supplementing with this hormone for a long time, while racking my brain trying to figure out a reason for the therapy to stop working on me and others over time… Well, interestingly and much to my surprise, I recently came across with some studies showing the powerful immune-suppressive effects of vitamin D (as powerful as any glucocorticoid), and even most worrisome, I read some studies showing that it inhibits the antigen-presentation process of dendritic cells, which lies at the very heart of the LDI mechanism. Actually, given that vitamin D is fat-soluble, it would make sense that it would accumulate in the body over time and that at one point it could prevent the therapy from working, especially taking into account that its immune-suppressive properties seem to be dose-dependent.
Well, for this reason I have performed a thorough review on vitamin D on chronic inflammatory diseases (such as ME/CFS), that maybe can be also helpful to some of you guys, as I think, after having done this review, that vitamin D supplementation could actually inhibit many therapies we follow.
Below is the summary of the article. attached is full text.
I hope it is helpful,
Best!
Sergio
************************
ABSTRACT
Low levels of the pre-hormone 25-hydroxyvitamin D (VD25) are normally shown in many chronic inflammatory diseases, and many studies show symptomatic improvements, lower rates of autoimmune diseases and fewer inflammatory markers, from taking vitamin D supplements. This has led many physicians and governments to argue that low levels of VD25 lie at the core of the pathogeneses of many conditions, and therefore vitamin supplementation is broadly recommended. However, some physicians and researchers defend the so called “alternate hypothesis”, which describes the low levels of vitamin D as a consequence of the chronic inflammation, instead of the cause. If the proponents of the alternate theory were right, vitamin D supplementation could be really dangerous; therefore, it is of imperative importance to review the available evidence and draw a solid conclusion on the matter.
One of the most important functions of vitamin D is exerted on the immune system. In this regard, when certain Toll-Like-Receptors (TLR) are activated, mainly on monocytes and macrophages, the circulating VD25 is converted into the active form 1,25dihydroxycholecalciferol (VD1,25) by the cells, which in turn induces the expression of antimicrobial peptides (AMPs) by binding to the nuclear vitamin D receptor (VDR). These peptides (mainly cathelicidins and beta defensins) constitute a major component of the innate immune system, showing activity against bacteria, fungi and viruses.
While the most accepted effect of vitamin D on the immune system is to enhance the innate immune response and to inhibit the acquired immunity, in vitro essays as well as interventional studies show contradictory results. In this vein, VD1,25 has demonstrated to block the conversion of Th1- and Th17- cytokines while promoting the Th2-immune response and the formation of Treg-cells. VD1,25 has also shown to inhibit the maturation and proliferation of dendritic cells (DC), to halter the antigen presentation capacity of DC and other antigen-presenting-cells, and to promote the anti-inflammatory and tolerogenic phenotypes of macrophages and DC. Furthermore, it has shown to induce hyporesponsivity in T cells and in peripheral blood mononuclear cells (PBMC), and to inhibit antibody secretion and autoantibody production by B-lymphocytes. Moreover, and in respect to the innate immunity, it has been reported that VD1,25 inhibits TLR2, TL4 and TLR9 as well as NK-cells.
There is a significant paradox, in that vitamin D is necessary for an efficient innate response against numerous intracelular pathogens, but at the same time, it has shown to impair both the innate and the Th1-mediated immune responses. In this vein, some of these discrepancies shown in the literature could be explained by the different doses of VD1,25 or VD25 used in the experiments. Thus, the studies using supraphysiological doses are those which show the most immunosuppressant effects of VD1,25, while some studies using physiological doses report, for example, that VD1,25 does not impede the Th1-mediated response or that the TLR and NK-cells are not inhibited by VD1,25 when lower doses are used. In any way, it seems clear after reviewing some of the literature, that the high VD1,25 serum levels found in patients with many chronic inflammatory and autoimmune conditions, can actually suppress significantly the immune system. In this regard, the anti-inflammatory properties and potency of VD1,25
(in considered physiological doses) and dexamethasone have been shown to be quite similar. Likewise, the inhibitory effect of VD1,25 on DC was shown to be very similar to the effect of glucocorticoids. In anyway, the effects of vitamin D supplementation observed in interventional studies are very useful in elucidating the effects of vitamin D on the immune system. In this regard, vitamin D supplementation in patients with multiple sclerosis, confirmed the promotion of tolerogenic DC, which in turn induced regulatory T cells and produced a shift toward T-helper-type 2 response. In this vein, PBMC responsiveness to disease-associated antigens was significantly reduced, while the signs and symptoms of the disease improved. Likewise, supplementation of vitamin D in patients with cystic fibrosis showed similar results.
Finally, at the end of this article, the “alternate theory” is described in detailed. This model proposes that, in chronic inflammatory and autoimmune diseases, intracellular microbes invade nucleated cells, inhibiting the VDR. This leads to high levels of VD1,25, low levels of VD25 and low-grade chronic inflammation and autoimmune processes produced by cross-reactivity, what would explain the symptoms of these diseases. When these conditions take place, AMPs cannot be properly expressed, what renders the immune system unable to eradicate the perpetuated infections. Thus, in this proposed-disease-model, extra vitamin D supplementation would be really harmful, as it can displace the VD1,25 from the VDR, blocking this receptor even more. In addition, vitamin D supplementation can further hamper AMPs production, what inhibits the innate response towards the intracellular pathogens even further.
If the alternate theory is accurate, the vitamin D supplementation in chronic inflammatory and
autoimmune diseases can be detrimental and dangerous, as it would allow the intracellular pathogens to spread, and the chronic situation would become even worse. Paradoxically, this can lead to transient symptomatic relief, in a way similar to that of many anti-inflammatory drugs.
Is the alternate theory supported by evidence? After a thorough review, we could conclude that it is. In this respect, low levels of VD25 are clearly associated with a wide variety of conditions; similarly, in many of these diseases the VD1,25 have been found to be elevated. In a similar vein, various pathogens have shown to down-regulate the VDR (including mycobacterium tuberculosis, mycobacterium leprae, aspergillus fumigatus, Epstein–Barr virus, HIV and borrelia burgdorferi). Finally, low levels of AMPs have been reported in some autoimmune conditions.
In summary, after an exhaustive review of the literature, we can conclude that low levels of VD25 are possibly due to the effects of chronic inflammation, and not the other way around. In this respect, and given the fact that the so called “alternate theory” seems to be well supported by the literature, it seems advisable to be very careful when it comes to vitamin D supplementation, especially in those with chronic inflammatory diseases.
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