So, I am reposting two of my posts from this previous thread and want to see if anyone wants to discuss the issues further.

I also would be interested to know more about the variations on the Marshall Protocol that others have mentioned that are being used. For instance, what is it that Scott Taylor is doing that is different? The Marshall Protocol sites want to keep things simple and stick to the original protocol, but I am glad to be able to discuss things in this forum more widely and freely.

I am getting ready to go out of town, so I may not be contributing in the next few days, but I look forward to reading what others have to say when I get back. It has been good to see many screen names of people that I used to see at the MP sites as well as some good friends. I hope we can discuss things in a friendly way, despite some differing perspectives as I know we all have the common aim of arriving at the truth about the best ways to get well and to help others get well. I think that should draw us together, even if we disagree on individual points. "The truth will out" and "people of good will may disagree" are two of my favorite expressions.

Joyce Waterhouse, Ph.D. http://members.aol.com/SynergyHN

Most of Post, with slight editing, from previous thread to start new topic on science related to MP and vitamin D
<<
I know this post is somewhat long and technical and may be difficult for readers who are not very familiar with the subject. One might look at the vitamin D article I mention (where many of the references can be found) and also an overview article of the MP that I wrote for Issue 7 of CISRA's Synergy Health Newsletter at http://members.aol.com/SynergyHN. I tried to make the overview article somewhat simpler.

By the way, although I am doing well on the MP myself, I am still independent and write on a variety of subjects, and do my best to study the science, sort things out and write them up to the best of my ability.

I have been researching the topic and trying to learn to what extent Trevor Marshall's data and views can be reconciled with other studies supporting more widespread vitamin D supplementation (Note for those new to Marshall Protocol: this idea of supplementing vitamin D is opposed to his approach, which involves minimizing vitamin D, sun and bright light, together with low dose pulsed antibiotics and using Benicar 120-160 mg/day in divided doses--but MP needs to be studied carefully before beginning).

First, I will address the issue of why some people at the MP sites with normal levels of 25 D and 1,25 D are being told the protocol is still appropriate for them. For one thing, as time has passed, they have found that in people with a clinical picture compatible with the MP and with these normal levels, they still tend to respond in the same way to the MP drugs. So now, they view the D tests as useful as indicating to a rough degree the degree of inflammation in areas of the body with plenty of blood flow (like heart and lungs), but perhaps more importantly, as a tool to rule out a TH2 viral process like AIDS or chronic hepatitis, where the 1,25 D was truly very low.

As Marshall explains, the paracrine or local levels of 1,25 D in areas with less blood flow, like joints, may be much higher. In addition, the body has a certain level of regulatory ability, particularly in the kidneys. If peripheral tissues are producing extra 1,25 D, most people's kidneys have the ability to slow production of 1,25 D in order to compensate and thus have the end result of a normal serum level. However, beyond a certain point and perhaps more so in different people (perhaps with more kidney inflammation?), this compensatory regulatory ability is exceeded by the unregulated production of 1,25 D in inflamed tissues.

My personal experience has been that I had been taking about 600-1000 IU vitamin D in supplements for most of my illness. Last August, when I had my D levels tested, my 25 D was fairly low at 11 ng/ml, but my 1,25 D was elevated at 65 pg/ml, well above the Merck maximum of 42, though near many lab's normal upper end. Thus, inflammation was causing a rapid conversion of 25 D to 1,25 D, just as in sarcoidosis.

My serum calcium levels were not the slightest bit elevated, so there appeared to me to be no reason to suspect that my 1,25 D was so high based on traditional criteria (this is usually the case with regard to serum calcium and 1,25 D values, according to Dr. Marshall's data). The calcium levels are of importance, since most of the reviews supporting higher vitamin D supplementation say that one can avoid excess 1,25 D levels by monitoring serum calcium, which they say will identify excess D levels. The new data being posted at the MP sites and published by Marshall show this is not an adequate way of monitoring for high 1,25 D.

I was surprised how much better I felt when I began avoiding D and sun and then began the Benicar. Of course, for some people, who's immune systems are in a different stage, they may feel worse on lower vitamin D. According to the MP theory, this is because the Herx symptoms may increase once the D is lower and the immune function begins killing the bacteria. Despite short term improvements, the potential for a later relapse may be there as the bacteria are able to continue to increase unhindered. And so it seems, if one is to evaluate whether the MP theory is correct, that short term improvements in a variety of studies may need to be reexamined, as the vitamin D may have been acting in a manner somewhat analogous to high doses of prednisone at least in certain illnesses (though it apparently differs from prednisone in that it mainly suppresses CWD bacterial killing, not all immune function).

According to Marshall, the above phenomenon of Herx suppressions can explain the improvement in many of the studies that claim vitamin D to be beneficial. In many cases, this seems to me to be feasible, though more data is needed. The studies are too short term to know if there is an ultimate benefit to this increased D level or if there would be an ultimate relapse. Even studies showing seasonal variation in MS lesions could be showing a process similar to what would happen if the patient was given immunosuppressive drugs only in the summer (instead of the greater sun exposure).

Regarding MS, I have several points to make (see article from Issue 7 at members.aol.com/SynergyHN for references). First, I think it may be true that very low levels of vitamin D that truly reflect a deficiency of active 1,25 D as well as the inactive precursor 25 D, might lead to a greater incidence of people getting MS to begin with. I see this as possibly being due to the fact that as with other hormones, we all need a level of 1,25 D in a certain range surrounding the mean for normal functioning. In far northern latitudes, where people, particularly older people are indoors or almost entirely covered up for a large part of the year, this may not happen, unless they consume enough vitamin D containing foods. But this doesn't necessarily mean that once one has MS, and the macrophages may be producing a lot of 1,25 D in response to CWD bacteria, that one would benefit by having so large an amount of vitamin D that it suppresses immune function.

Second, to my knowledge, only one epidemiological study seems to show that there is better survival for MS patients who have outdoor jobs and thus presumably more vitamin D. I will just say that these kind of epidemiological studies have a lot of potential for bias. For instance, people choose their jobs for all sorts of reasons that could correlate with characteristics of their disease and influence the results, and I think it unwise to base too much on this study alone.

However, even if it turned out that this study's conclusions were validated, it may just mean that immune suppression with high D limited inflammatory damage to some degree and extended their life a little longer (as opposed to sarcoidosis, where it would seem to be more likely to hasten their death). But that doesn't mean that low D plus the MP's treatment or perhaps other antibacterial treatment of a proposed bacterial cause wouldn't have far better results than giving just vitamin D. Perhaps the antibiotic based treatments might even cure the disease.

As for the animal studies showing a benefit of vitamin D in autoimmune illnesses, there are also many problems. The mouse model for the autoimmune diseases involves causing a condition that looks similar to MS or other AI diseases by injecting certain antigens into the animal. It may be that they are able suppress the immune reaction to the antigens with too much vitamin D, and if this is the case, it is not surprising that the disease would improve. But, if this is not a true model of the disease, but it is actually caused by bacteria that would eventually proliferate more with immune suppression, the mice experiments are probably of little value. There are other problems too, like the experiments are short and mice are adapted to much dirtier environments, but I personally find the first reason most convincing.

I have also begun looking at the data for cancer, especially looking at the work of William Grant, Ph.D., (www.sunarc.org) who does a lot of epidemiological cancer research. He sent me a very recent paper he wrote where he discusses data that shows that prostate cancer rates had a J shaped relationship with light intensity (Int. J. Cancer. 111:470-471, 2004). His brief article also cited a paper (Tuohiman et al., Int. J. Cancer 108:104-8, 2004) that showed the lowest prostate cancer rates were in the range of 40-60 nmol/l (about 16-24 ng/ml) and this was supported by the correlation being J shaped when looking at the relationship between living at various latitudes and prostate cancer.
This J shaped curve suggests that people with too high a level of vitamin D are more prone to get prostate cancer than those in the moderate range for D. For the study that actually measured 25 D, those with too low a level of 25 D (the inactive precursor) could reflect two different situations, and perhaps both may occur. The very low 25 D may be associated with a true deficiency and in that case the active hormone, 1,25 D would also be very low and supplementation might be appropriate. However, the 25 D could also be low due to a TH1 inflammatory process depleting the 25 D precursor through conversion by macrophages into 1,25 D. In that case, the 1,25 D would then be high and supplementation would be inappropriate. Clearly, these two different possibilities to explain low 25 D can not be distinguished until studies start also measuring 1,25 D.
I do think that the studies that showed evidence for higher colon cancer mortality rates in parts of the world with very low light levels might suggest that very low levels of sun exposure might increase the colon cancer mortality rate, especially since calcium deficiency has also been linked independently with colon cancer (Grant et al, Nutrition and Cancer 48(2): 115-123.) It may be, however, that if everyone got adequate calcium, that the D levels would no longer be a factor. It is also interesting that the above relationship for colon cancer did not hold up for women, when the data were analyzed separately in several studies. It seems to me that the higher rate of autoimmune and related diseases in women, (presumably the undiagnosed cases, as obvious cases would probably have been excluded from the study) might have caused the correlation to disappear. In women, the 1,25 D levels might be more frequently elevated due to TH1 disease, so even very low light exposure would not cause them to be deficient.

For breast cancer, the relationship with D was weaker, and other dietary factors seemed to be much more important (Grant, Cancer 94:272-81, 2002). I have yet to look further into this data, but I thought it interesting that I have seen maps of the U.S. showing breast cancer in the areas of highest industrial activity (CIIN conference, 2004, ciin.org). These areas were in the Northeast, especially. This relationship might confound the vitamin D effect for the U.S., as a large part of the breast cancer correlation was related to finding higher cancer rates in the Northeast, as compared to the Southwest. But I need to look into this more.

Another area I plan to look into is the relationship some have observed between sun exposure, vitamin D and depression. I know my own mood fluctuations have improved since I lowered D, while others have responded differently. The link between inflammation and depression and other mental disorders has received a lot of interest of late. Many of us experience this link when we undergo Herx reactions and feel rather depressed and/or anxious, even having bad dreams on the nights of our biggest Herxes due to the antibiotics. I intend to look further into this in future, but it seems possible that at least some cases of depression being helped by sun or vitamin D could be due to high levels of D suppressing the inflammation from Herxes (occurring when the immune system kills CWD bacteria).

I plan to write a more detailed article on these issues in the coming months, but I thought I'd share these preliminary observations. I hope they may be of some help in giving a different perspective on this complex subject.

Best Wishes to All,
Joyce Waterhouse, Ph.D.
(for those who are interested, information on my background can be found at http://members.aol.com/SynergyHN and http://members.aol.com/jcwat101, but I will say briefly that I have a bachelor's in Biology (much of it pre medical), a Ph.D. in Systems Ecology with a minor in Statistics from U.T. Knoxville, did research at Oak Ridge National Laboratory, and published several papers in scientific journals before becoming ill with chronic fatigue and immune dysregulation syndrome (CFIDS or CFS), fibromyalgia and Lyme Disease. Since then I have spent nearly 20 years studying these and other illnesses, including reading a number of medical textbooks)

On the 1,25 D as an indicator of TH1 immunity, I think one has to look at the entire body of Marshall's recent writings and look at the references (like Mawer et al, Evidence for Nonrenal Synthesis of 1,25 -Dihydroxyvitamin D in patients with inflammatory arthritis, J. Bone and Mineral Res. 6(7): 1991) as well as Abreu et al, which I post the abstract for below. The basic fact that activated macrophages in sarcoidosis produce 1,25 D is well-known and can be found in any textbook (like Harrison's Principles of Internal Medicine). But the use of it more widely as an indicator is something fairly new, though supported to some degree by the Abreu et al and Mawer et al and other studies in molecular medicine. If it were something widely established, then Marshall's work wouldn't be considered so innovative. The references I've looked at cited by Marshall do suggest it to be a promising way of looking at things and there are a number of references that support the underlying processes (and I also cite and discuss some of them in my vitamin D article at http://members.aol.com/SynergyHN ). His work makes the leap of connecting all the basic research he cites with his newer observations. But I agree, there is still much more work to be done.

On the AIDS study, I am going by the one cited in Marshall's Autoimmunity Review article (Haug et al 1998). See http://trevormarshall.com/papers.htm for links to all his papers and within those papers you will find many of those he cites, including this one. Haug finds an average for 1,25 D in HIV infected patients of 48 pmol/L. I think the misunderstanding has arisen because they are using different units. To convert to the units used usually in the U.S., you have to divide by about 2.5 to get 18.5 pg/ml (they also state that sometimes the 1,25 D is undetectable, which I suppose may be related to the severity of the infection). This 18.5 is a lower value than I recall seeing posted at the Marshall Protocol.com site. If any were near that, they would have suggested a retest if the sample may have not been frozen or consideration of another diagnosis.

I think with regard to the Mycobacterium, the cause and effect may be reversed, since in HIV the the factor of the destruction of the TH1 immune system is there, which is not occurring in sarcoidosis. Perhaps they are having the Mycobacterium problems because their TH1 immune systems have declined to the point that they have virtually no TH1 cells to fight off the bacteria and thus also have little 1,25 D being produced by macrophages (part of the TH1 response).

I can also say that Dr. Marshall has also analyzed some of the same data that Vieth uses and disagrees with many of his interpretations of it. He is not the only one that disagrees, since Vieth is pushing for higher requirements and a different way of looking at D than the established one.
This is clear from his disagreement with the establishment that he expresses in the first 2 sentences of this abstract:

<Author: Vieth R
Source: J Steroid Biochem Mol Biol, 89-90(1-5): 571-3 2004
Abstract: Official nutrition committee reports in both North America and Europe now state that Vitamin D is more of a hormone than a nutrient. These statements are wrong, and do not reflect the definitions of either vitamin or hormone.>>

I have still to look more deeply into Vieth's work myself, but another example that would seem to contradict Vieth's work is this study by Adams et al ( http://www.annals.org/cgi/content/full/127/3/203 ) involving generally healthy patients rather than ones with TH1 disease, who have had bone loss due to too much 25 D from supplements (much of it not even being on the label). Some of their data in Table 1 and the graphs, shows that they were losing bone at some of the levels of 25 D that Vieth seems to think to be O.K. or even recommended (remember to divide by 2.5 for 1,25 D and 2.6 for 25 D). Their bone mineral density improved by stopping D supplementation.

The amount they took would have been a much greater problem if they had sarcoidosis or a related disease with D dyregulation. If one looks at the data in Table 1, their 1,25 D levels aren't nearly as high as they would be in a sarc. patient, given their very high 25 D levels.

I don't mean to say that some of the studies showing that older people, especially who live in the North, like in Canda or Finland etc... may not need more vitamin D in their diet for osteoporosis prevention. But I think Vieth goes too far in the levels he recommends and he doesn't know about this new data that shows that the situation of sarcoidosis, of dysregulated vitamin D, is not just a tiny fraction of the public, but may occur in more like 5-10 %. I also don't think his view that a certain amount of increase of PTH is necessarily synonymous with bone loss, and I don't think it is accepted very widely yet by others either, but the PTH part is something I need to look into more.

This paper by Abreu et al., on Crohns and Ulcerative Colitis (see abstract below), indicates that 60 pg/ml of D or greater would be detrimental and lead to bone loss. They use a somewhat higher cut off for the point at which bone loss occurs than the 45 pg/ml, but lower than my own 1,25 D value, I believe. I don't know the basis for Merck's value, but I believe there is one, and will have to get back to you on that. In any case, the issue of bone loss isn't what is most significant in Marshall's use of the 1,25 D test, which he is now using as an indicator, though not a perfect one, of the TH1 vs TH2 dominance.

Title: Measurement of vitamin D levels in inflammatory bowel disease patients reveals a subset of Crohn's disease patients with elevated 1,25-dihydroxyvitamin D and low bone mineral density.
Author: Abreu MT , Kantorovich V , Vasiliauskas EA , Gruntmanis U , Matuk R , Daigle K , Chen S , Zehnder D , Lin YC , Yang H , Hewison M , Adams JS
Source: Gut, 53(8): 1129-36 2004
Abstract: OBJECTIVES: Many patients with Crohn's disease (CD) have low bone mineral density (BMD) that may not be solely attributable to glucocorticoid use. We hypothesised that low BMD in patients with CD is associated with elevated circulating levels of the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)(2)D). We further hypothesised that this was secondary to increased synthesis of 1,25(OH)(2)D by inflammatory cells in the intestine. The aim of this study was to examine the relationship between 1,25(OH)(2)D levels and BMD in patients with CD. METHODS: An IRB approved retrospective review of medical records from patients with CD (n = 138) or ulcerative colitis (UC, n = 29). Measurements of vitamin D metabolites and immunoreactive parathyroid hormone (iPTH) were carried out. BMD results were available for 88 CD and 20 UC patients. Immunohistochemistry or real time reverse transcription-polymerase chain reaction (RT-PCR) for the enzyme 1alpha-hydroxylase was performed on colonic biopsies from patients with CD (14) or UC (12) and normal colons (4). RESULTS: Inappropriately high levels of serum 1,25(OH)(2)D (>60 pg/ml) were observed in 42% of patients with CD compared with only 7% in UC, despite no differences in mean iPTH. Serum 1,25(OH)(2)D levels were higher in CD (57 pg/ml) versus UC (41 pg/ml) (p = 0.0001). In patients with CD, there was a negative correlation between 1,25(OH)(2)D levels and lumbar BMD (r = -0.301, p = 0.005) independent of therapeutic glucocorticoid use. 1,25(OH)(2)D levels also correlated with CD activity. Lastly, immunohistochemistry and RT-PCR demonstrated increased expression of intestinal 1alpha-hydroxylase in patients with CD. CONCLUSIONS: These data demonstrate that elevated 1,25(OH)(2)D is more common in CD than previously appreciated and is independently associated with low bone mineral density. The source of the active vitamin D may be the inflamed intestine. Treatment of the underlying inflammation may improve metabolic bone disease in this subgroup of patients.

In response to another question, I believe I did feel some improvement on lowered D before I started the Benicar, and others have reported this, also.

On the subject of whether taking vitamin D might protect against diabetes, it is intriguing, and I plan to look into that research. But it may fall into the situation I suggested might be true of MS, that a deficient vitamin D state might allow the bacteria to become established, but it doesn't necessarily follow that too much D would be beneficial after it is established. Just like with other hormones, being hypo is as bad as being hyper. But more needs to be researched on this.

But I should note that a very new study by a well-known researcher (see Marshall's discussion of this on the upcoming DVD from the conference from http://autoimmunityresearch.org for more on this) found that in mice that typically got diabetes, inoculation with bacterial antigens in their first 5 weeks caused a dramatic reduction in the rate at which they got diabetes.
I don't argue that a truly deficient vitamin D level might not be harmful to immunity, in fact I think it is, but it may be that an even more effective prevention method might eventually turn out to be an immunization to certain bacteria.

I also wanted to say on the subject of whether very low mino. levels might really promote bacterial growth, although it might occur in certain circumstances with certain bacteria, that did not at all fit with my experience. The first dose I used on the MP was 3 mg Mino (at a time before they changed the recommendation to begin at 25 mg) and I did get a big Herx. within the first 12 hours (bigger than with 100 mg Mino pre-MP). But over time, the Herxes at the 3 mg dose declined to hardly noticeable, indicating that my immune system, working with the antibiotic, had mostly killed off the bacteria that could be reached using that dose of that one drug. Each time the dose was raised, it seemed as though the Mino was penetrating a little deeper and reaching new bacteria, and then the Herx declined after a while at each dose. I can't think of any more plausible explanation of this pattern of response, since it has also been accompanied by improvements in my health.

I think the pulsing and low doses of antibiotics may well be more effective than constant dosing, particularly if one thinks of it as being the immune system that is really doing the killing and it's not simply the antibiotic, which just weakens the bacteria. The way I view it at present, is that too big an initial die-off with too big a dose of antibiotics may raise the inflammation and 1,25 D levels, which then help suppress the immune killing of the bacteria. But it is probably a lot more complicated than that.

However, my point on pulsing is that the bigger Herx at 3 mg on the MP than 100 mg pre-MP in the first 12 hours supports the view that its not only the pulsing that is the difference with the MP, because when comparing only the very first 12 hours of Herxing from the first dose, pulsing can not become an issue. I'm sure there are others on the MP who have done pulsing before they got on the protocol and probably could directly address the issue of whether the MP enhanced the effect independent of the pulsing.

On the issue of fluctuations of 1,25 D with ovulation, I think they may have some relevance for women who are menstruating. But I noticed that paper was rather old and the technique they used was quite new at the time they published and they had only a small sample size, so I'm not sure how much it can be relied on by itself.

I promised myself that one day I will bite into this protocol. Presently, however, I know too little to debate it.

I would like to revisit the topic in a few months and perhaps find more time to study it.

Also, perhaps there is a better forum to discuss it than this one.

The Administrators of Lymenet may create a separate forum titled MP for such discussions so more scientifically oriented or simply interested in the topic people could enter.

But not all the posts in this thread need to be so scientific. I just felt I needed to do my best to thoroughly answer the previous posts, to the best of my ability.

I am also posting now to let people know that the DVDs of the Chicago conference on the Marshall Protocol and related topics can now be ordered from http://autoimmunityresearch.org/chicago2005.htm . These DVDs include both very technical and fairly non technical information.

Also, for those who are interested in Diabetes and possible connections with other autoimmune diseases, Lyme and vitaim D, which I mentioned above in response to a previous comment, I now know the researcher's name who I mentioned above, who's research Trevor Marshall, Ph.D. discussed at the conference. The researcher's name is JF Bach. Dr. Marshall mentioned the following study, and then described more recent work presented at a conference in Budapest last year that showed inoculation of certain mice with certain bacteria, prevented diabetes, if the inoculation (or vaccination) occurred within the first 5 weeks. Thus, Dr. Marshall regards this as additional support for the causal role of bacteria in a variety of autoimmune diseases, as discussed in more detail at the conference.