I understand that you are trying to help your sister and that’s very admirable. However, right now I am in graduate school and extremely busy. I have kept the comment sections open on this site so that I can answer people who ask one or two questions but I simply don’t have the time to spend hours discussing your concerns.

Since we are a non-profit organization in which nobody gets paid we have very limited resources and time. Most of the people who start the MP seem to get most of the info they need by using our Knowledgbase, reading our publications, and using http://www.curemyth1.org to meet other people on the treatment and ask them about progress and concerns. If you feel that these resources do not offer you enough information about the MP to recommend the treatment to your sister then perhaps she should seek out another treatment option at this time. Maybe in the future we will have the resources to provide more individualized counseling.

Best,

Amy

Paul- Thank you for your reply, but I was a bit put off by your email to me:

“Author: Paul Albert
Comment:
Bill,

Let me get this straight – you posted your book-length comment in three places??? Not cool.

Well, anyway I responded to one of them here:
http://bacteriality.com/about-2/

Paul”

Not cool? I’m trying to find answers for my sister who is very ill. I figured the more places I posted, the more information and perspectives I might get. Perhaps you could be more welcoming. I don’t have a dog in this fight (and fight it seems to be judging by what I’ve seen on occasion from both sides).

Also, I don’t see my original post here for others to read, so it will be hard for them to follow your responses to me.

I have some genuine, sincere, objective questions and I need straight forward, compassionate answers.

“As for the relative lack of data supporting our claims, we are not the ones making the non-conservative recommendation to supplement with a secosteroid.”

1. Not all cholecalciferol is converted to 25D. Some is stored. Cholecalciferol is not a secosteroid (at least I don’t think, correct me if I am wrong, it is a pre-hormone, 25D is a secosteroid after cholecalciferol is converted).

2. If your recommended level for MP people to get below is 32ng/ml, this is not what I have seen on the forums. I have seen people well under 20, even 10-12 or lower. If it is not your intention for people to go this low then there needs to be better information. If it is intended for people to go this low, I would say this is not a “conservative” recommendation– just as you say the pro-D side, I belive there is a general lack of data supporting people avoiding D until their levels are in the low teens or lower. The only data you have supporting this is ‘in silica’. This is far from ideal data to base recommendations on.

Another common theme I see in MP anecdotes is the ‘IP’ reactions that used to be referred to as ‘herx’ reactions. It seems any adverse effects from this treatment are all attributred to these ‘IP’ reactions, almost encouraging the patient that the treatment is working and to move forward, and rarely if ever attributed to side effects of medication like the high and frequent dosing of Benicar– ARB’s are known to cause low aldosterone levels, especially at higher doses and this can produce many of hte same symptoms that are being classified as ‘IP’.

Maybe the pro-D side doesn’t have as long term data as you would like, but there certainly are some long term studies. The MP has none. At least not that I am aware of. No long term, randomized, controlled trials, just anecdotes. I do not doubt that some people are getting better, but no one, not even you, Amy Proal or even Trevor Marshall can tell me or anyone else exactly why. Is it perhaps the Benicar alone? Is it the long term dosing of antibiotics alone? As some people are on MP for years, with multiple variable like changes in diet, awareness of health, fitness, etc., you simply cannot say for sure what is helping them. You have no in vitro, much less in vivo data to prove any part of the MP protocol theory. No data besides ‘in silica’ to prove Benicar activates the VDR, and likewise to prove 25D is immunosuppressive.

Further, correct me if I am wrong, but I believe that your reference range for 1,25D is outdated at 45 for the upper limit. It seems more current lab tests and studies show this to be closer to 60-65.

Also, I’ve not seen any evidence in your protocol testing recommendations that takes into account the effect of calcium, PTH, Phosphate and others on 1,25D levels.

Correct me if I am wrong, but the studies I’ve seen show that levels of 25D below 20ng/ml tend to cause marked increases in PTH, which can precipitate bone loss.

To get back to a point I alluded to earlier. I’ve not seen sufficient evidence from your MP information that 25D or other inactive forms can effect the function of the VDR. Here are some references I found to support the opposite:

http://www.ncbi.nlm.nih.gov/pubmed/9398723?dopt=Abstract

These are on the binding affinity of 25D compared to 1,25D, one showing 25D’s is at least 500x lower than 1,25D’s binding affinity for the VDR:

http://www.ncbi.nlm.nih.gov/pubmed/1084355?dopt=Abstract

I’ve heard reports of even 1000x lower, but I am still searching for an adequate reference.

To be fair, I had the common sense thought that 25D levels are many times higher in the serum versus 1,25D, given that 25D levels are measured in ng/ml and 1,25D levels are measured in pg/ml, and perhaps the relative abundance of 25D to 1,25D might overcome this binding deficit. However, when I explored this angle, it seems that 25D has a higher tendency to remain protein bound in the serum versus 1,25D by a nearly 10-fold amount.

Further, I found a study on sarcoidosis where they bound radioactive 1,25D to VDR receptors on T cells. They found that 25D was not able to displace the radioactive 1,25D but that non-radioactive 1,25D was able to displace it:

http://www.ncbi.nlm.nih.gov/pubmed/1646583?dopt=AbstractPlus

I cannot seem to find one study that demonstrates that 25D affects the VDR and inhibits 1,25D’s ability to turn it on. Further, correct me if I am wrong because I am just learning about all of this, but from what I have read and understand so far about the relationship between 25D and PTH, if 25D did block the activity of 1,25D on the VDR, then wouldn’t PTH levels increase? Rather, it seems that the higher 25D goes, PTH is decreased.

What I would believe is if you had a study in human volunteers that took baseline 25D, 1,25D, PTH, Calcium, and antimicrobial peptide levels at baseline, then randomized and groups to receive D supplementation at a level targeted to get 25D levels into the 40-60ng/ml range. A placebo group, and a group for D-avoidance targeting low 25D levels and see what happens to antimicrobial peptide production and perhaps other immune markers. This would show id low 25D would indeed boost immune response, allowing 1,25D to active the VDR, or perhaps show that increased 25D levels decrease AMP production or other immune markers.

Also, to allude to an earlier point, to prove MP works, you need studies with multiple arms– perhaps a benicar only arm, a low D only arm, low D + abx, Benicar + abx, etc., etc. Perhaps Benicar and abx is enough? Perhaps low D is harmful long term? (You have no long term data, certainly no where near the number of years as some of the D-supplementation studies). MP and D-Avoidance simply have not been around long enough to bear out an potential long term health effects.

Now, after all this, this is not to say I am going to go out an gob down oodles of cholecalciferol, but I don’t think I’m going to recommend my sister starve herself of sun exposure or dietary D intake either.

I also don’t mean to be at all hostile, though your email to me certainly was. I am just a brother who loves his sister very much and would genuinely like to help her. I am looking fo conrete answers, and any information or clarification you can provde me on the points I have made here will be most helpful. I appreciate your time and that of the other volunteers on this and other sites.

“Author: Paul Albert
Comment:
Bill,

Let me get this straight – you posted your book-length comment in three places??? Not cool.

Well, anyway I responded to one of them here:
http://bacteriality.com/about-2/

Paul”

Not cool? I’m trying to find answers for my sister who is very ill. I figured the more places I posted, the more information and perspectives I might get. Perhaps you could be more welcoming. I don’t have a dog in this fight (and fight it seems to be judging by what I’ve seen on occasion from both sides).

Also, I don’t see my original post here for others to read, so it will be hard for them to follow your responses to me.

I have some genuine, sincere, objective questions and I need straight forward, compassionate answers.

First, to your point on no salaries being paid to anyone including Dr. Marshall, that is all well and good for now, I am sure you are aware that Dr. Marshall has a US Patent application for his protocol.

“As for the relative lack of data supporting our claims, we are not the ones making the non-conservative recommendation to supplement with a secosteroid.”

1. Not all cholecalciferol is converted to 25D. Some is stored. Cholecalciferol is not a secosteroid (at least I don’t think, correct me if I am wrong, it is a pre-hormone, 25D is a secosteroid after cholecalciferol is converted).

2. If your recommended level for MP people to get below is 32ng/ml, this is not what I have seen on the forums. I have seen people well under 20, even 10-12 or lower. If it is not your intention for people to go this low then there needs to be better information. If it is intended for people to go this low, I would say this is not a “conservative” recommendation– just as you say the pro-D side, I belive there is a general lack of data supporting people avoiding D until their levels are in the low teens or lower. The only data you have supporting this is ‘in silica’. This is far from ideal data to base recommendations on.

Another common theme I see in MP anecdotes is the ‘IP’ reactions that used to be referred to as ‘herx’ reactions. It seems any adverse effects from this treatment are all attributred to these ‘IP’ reactions, almost encouraging the patient that the treatment is working and to move forward, and rarely if ever attributed to side effects of medication like the high and frequent dosing of Benicar– ARB’s are known to cause low aldosterone levels, especially at higher doses and this can produce many of hte same symptoms that are being classified as ‘IP’ reactions.

Maybe the pro-D side doesn’t have as long term data as you would like, but there certainly are some long term studies. The MP has none. At least not that I am aware of. No long term, randomized, controlled trials, just anecdotes. I do not doubt that some people are getting better, but no one, not even you, Amy Proal or even Trevor Marshall can tell me or anyone else exactly why. Is it perhaps the Benicar alone? Is it the long term dosing of antibiotics alone? As some people are on MP for years, with multiple variable like changes in diet, awareness of health, fitness, etc., you simply cannot say for sure what is helping them. You have no in vitro, much less in vivo data to prove any part of the MP protocol theory. No data besides ‘in silica’ to prove Benicar activates the VDR, and likewise to prove 25D is immunosuppressive.

Further, correct me if I am wrong, but I believe that your reference range for 1,25D is outdated at 45 for the upper limit. It seems more current lab tests and studies show this to be closer to 60-65pg/ml.

Also, I’ve not seen any evidence in your protocol testing recommendations that takes into account the effect of calcium, PTH, Phosphate and others on 1,25D levels.

Correct me if I am wrong, but the studies I’ve seen show that levels of 25D below 20ng/ml tend to cause marked increases in PTH, which can precipitate bone loss.

To get back to a point I alluded to earlier. I’ve not seen sufficient evidence from your MP information that 25D or other inactive forms can effect the function of the VDR. Here are some references I found to support the opposite:

http://www.ncbi.nlm.nih.gov/pubmed/9398723?dopt=Abstract

These are on the binding affinity of 25D compared to 1,25D, one showing 25D’s is at least 500x lower than 1,25D’s binding affinity for the VDR:

http://www.ncbi.nlm.nih.gov/pubmed/1084355?dopt=Abstract

I’ve heard reports of even 1000x lower, but I am still searching for an adequate reference.

To be fair, I had the common sense thought that 25D levels are many times higher in the serum versus 1,25D, given that 25D levels are measured in ng/ml and 1,25D levels are measured in pg/ml, and perhaps the relative abundance of 25D to 1,25D might overcome this binding deficit. However, when I explored this angle, it seems that 25D has a higher tendency to remain protein bound in the serum versus 1,25D by a nearly 10-fold amount. So given that ng are 1000x a pg, and for a mathematical example a person had a 25D level of 40ng/ml and 1,25 level of 40pg/ml, ther ewold be 1000x more 25D; however, if 25D is roughly 10x more protein bound versus 1,25D, this would theoretically leave 100x as much free 25D than 1,25D, with 1,25D having at least a 500x affinity for the VDR– I think the 1,25D wins here.

Further, I found a study on sarcoidosis where they bound radioactive 1,25D to VDR receptors on T cells. They found that 25D was not able to displace the radioactive 1,25D but that non-radioactive 1,25D was able to displace it:

http://www.ncbi.nlm.nih.gov/pubmed/1646583?dopt=AbstractPlus

I cannot seem to find one study that demonstrates that 25D affects the VDR and inhibits 1,25D’s ability to turn it on. Further, correct me if I am wrong because I am just learning about all of this, but from what I have read and understand so far about the relationship between 25D and PTH, if 25D did block the activity of 1,25D on the VDR, then wouldn’t PTH levels increase? Rather, it seems that the higher 25D goes, PTH is decreased.

What I would believe is if you had a study in human volunteers that took baseline 25D, 1,25D, PTH, Calcium, and antimicrobial peptide levels at baseline, then randomized and groups to receive D supplementation at a level targeted to get 25D levels into the 40-60ng/ml range. Perhaps a placebo group, and a group for D-avoidance targeting low 25D levels and see what happens to antimicrobial peptide production and perhaps other immune markers. This would show if low 25D would indeed boost immune response, allowing 1,25D to activate the VDR, or perhaps show that increased 25D levels decrease AMP production or other immune markers.

Also, to allude to an earlier point, to prove MP works, you need studies with multiple arms– perhaps a benicar only arm, a low D only arm, low D + abx, Benicar + abx, Benicar + low D, Benicar + low D + abx, etc., etc. Perhaps Benicar and abx is enough? Perhaps low D is harmful long term? (You have no long term data, certainly no where near the number of years as some of the D-supplementation studies). MP and D-Avoidance simply have not been around long enough to bear out an potential long term health effects.

Now, after all this, this is not to say I am going to go out an gob down oodles of cholecalciferol, but I don’t think I’m going to recommend my sister starve herself of sun exposure or dietary D intake either.

I also don’t mean to be at all hostile, though your email to me certainly seemed to be. I am just a brother who loves his sister very much and would genuinely like to help her. I am looking for conrete answers, and any information or clarification you can provde me on the points I have made here will be most helpful. I appreciate your time and that of the other volunteers on this and other sites.

1. I believe the number we use these days is lower than 32 ng/ml. Lately, we’ve been talking about <20. Though there are certainly others, I think the main reason that figure is used because that is the amount of 25-D in patients who don't supplement with vitamin D:
http://mpkb.org/doku.php/home:pathogenesis:vitamind
http://mpkb.org/doku.php/home:tests:25d

Keep in mind that 1,25-D levels are often elevated in patients sick with chronic disease – something you don't hear too much about from the pro-supplementation crowd.

2. We address many of these questions here:
http://bacteriality.com/2009/08/10/iom/
http://mpkb.org/doku.php/home:othertreatments:sunshine
http://mpkb.org/doku.php/home:pathogenesis:vitamind:latitude
http://mpkb.org/doku.php/home:pathogenesis:vitamind:observational_bias

3. There are *some* long-term studies on vitamin D intake :
http://mpkb.org/doku.php/home:pathogenesis:vitamind:longterm

As for the relative lack of data supporting our claims, we are not the ones making the non-conservative recommendation to supplement with a secosteroid.

4. Once again, see here:
http://bacteriality.com/2009/08/10/iom/

5. The problem with historical efforts to understand which level 25-D is immunosuppressive is that these studies often need to account for 1,25-D. Short-term administration of vitamin D can raise levels of 25-D and increase VDR activity but only because some of that 25-D is converted into 1,25-D. There's a lot to explain here. Read some of the MPKB articles I linked to above to get more on our explanation for this.

6. What kind of market exists for the MP? Currently, no one associated with ARF receives a salary. I can assure you that there is *no* money made in any other way. For example, ARF does not make any money when patients buy special glasses from NoIR Medical. Anyone who is making money off the MP is not associated with ARF. So… at this point, the compensation is all psychological.

I think it would be great if the Foundation could pay Dr. Marshall a salary. Maybe that will happen in time…. That said, there are better ways to make money than convincing doctors and researchers that several of their key assumptions about chronic disease are incorrect.

By the way, here's an introduction to the MP:
http://mpkb.org/doku.php/home:patients:protocol_overview

The MPKB is still a work in progress, but there is some helpful stuff there.

Best,
Paul

Here are our list of papers and presentations:
http://mpkb.org/doku.php/home:publications

And here is our 2008 survey:
http://mpkb.org/doku.php/home:publications:mp2008_survey

Also, we do have a clinical trial in the works:
http://bacteriality.com/2009/07/22/wch/

Best,
Paul

Has the MP undergone a clinical double blind study to test its effectiveness to heal/cure autoimmune diseases? Have studies of the MP been published in any scientific or medical journal?

Thanks and regards,
Ian

I’m in graduate school now getting my PhD. I’m really busy writing other stuff these days. I would like to write a Part III to my recovery from CFS, but it always seems to be put on the backburner. So, I’ve tried to make people aware of my improvements through my actions rather than my words including pictures of trips, etc. Although it has improved, I still struggle with photosensitivity. I usually take off my glasses when photographed, but I do typically wear them in the bright sun.

I assume you’re aware that the thinking has a shifted quite a bit in terms of the mentality surrounding recovery and the MP. Whereas Dr. Marshall once advocated that people needed to get Phase III in order to beat their disease, various case histories have suggested that patients can remain on Phase II or even Benicar alone and still recover tremendously.

So, I hope if you haven’t already, you will begin to see some improvement in the coming year. I’m glad you’re sticking with the MP. Thank you for your kind comments about my talks and presentations. I have some more coming up that I’m eager to work on.

Take care and at some point, I hope to write Part III.

Best,
Amy

Is there a chapter 3 yet to your Journey towards Complete Recovery from CFS ….?

You are functioning, travelling, no Noirs (that I see),, you give me hope!!!! I have been super photosensitive, 2 years on MP and not tolerating much daylight yet. Since I am probably twice your age…I have quite a load of CWDs
with much appreciation
Heather Beckett, Canada

My thesis advisor was just preparing to recruit more students to make a research team focusing on L-form bacteria. By then, I will be a member in that research team since I was the one working in this field at first and kept this research coming so far. Although I made a bare contribution to it, at least we’ve had a start. I havn’t went to lab for nearly three months because I was busy writting my Master’s thesis as well as dealing with a number of papers for application to persue a PhD position abroad. But sooner or later,I’ll continue my research again. Before that, I have to finish all my paper work as I know once the experiment set out, there’s no recess.

Watching your Web makes me feel my deficiency in this area and there are so much more I have to learn if I really want to go on the research. I think maybe I don’t have the ability you expected to help your trial, but if any, I would try my best to do it. After all,it’s very nice to know you online and hope we will see each other someday.

Truly yours,

Wen Zhen

P.s: I’m also not a local here, so what you went through is pretty the same to me.

Wow! I can’t believe you are working at West China Hospital and studying L-form bacteria!! That’s quite a coincidence. I wish you had written me last week because I was in Chengdu last week and for a week or so before that. Over the last week I’ve been in Australia which is why I haven’t written back to your comment more quickly.

Our trial is moving forward and we are working with researchers in the rheumatology department. That is because the first trial we are doing will test the Marshall Protocol on patients with ankylosing spondylitis.

However if you read through the material on this site you’ll see that we believe L-form bacteria and other bacteria (including biofilm bacteria) play a causative role in a wide array of diseases. So I definitely think that you are doing research on a fascinating topic!

I’ve heard that it’s definitely very difficult to culture L-forms so I can understand why some of your experiments might have failed. But if you say you’re becoming more familiar with the L-form I think that’s wonderful and that your studies will make a serious contribution to medicine.

Perhaps you could help out with our trial at West China Hospital. I will email you privately in a few days with more details. At the very least you could meet the research team. Also next time I come back to Chengdu (hopefully in a few months) we have to meet!

I like Chengdu a lot. The food is very spicy though and I have trouble eating spicy food so my meal options are a bit limited. I’ve seen the pandas twice and gone to most of the main sights in Chengdu. I also sang Karaoke at ATT with students from the rheumatology department. It was really fun!

Hopefully we’ll keep in touch and I’ll write you privately soon.

Best,

Amy