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- ​====== Presentation - Vitamins D in chronic disease ====== 
- 
- 
-**Type:** Presentation\\ 
-**Presenter:​** ​ Joyce Waterhouse, PhD\\ 
-**Conference:​** ​ Recovering from chronic disease - sarcoidosis,​ autoimmunity,​ AIDS and cancers\\ 
-**Location:​** ​  Los Angeles, CA\\ 
-**Date:​** ​ June 17-18, 2006\\ 
-**Related content:** [[http://​autoimmunityresearch.org/​transcripts/​waterhouse_lax2006.pdf|slides and transcript]]\\ ​ 
- 
- 
- 
-===== Transcript ===== 
- 
- 
-Hi. I hope your coffee break has you all alert enough that I won’t 
-put you to sleep. Actually, I think there is some exciting new 
-information here, and I hope it will interest you. 
-The title here refers to vitamins D, no that isn’t a typo, we use 
-vitamins D since there are many forms of vitamin D. Actually, it is 
-not really a true vitamin, since our bodies produce it, with the aid 
-of the sun. It is actually better, in our view, to think in terms of a 
-steroid hormone and it’s precursors. 
- 
-You might ask, why is vitamin D important? As you probably know, 
-the Marshall Protocol or MP that we have been discussing at this 
-conference includes a reduction of vitamin D to help improve 
-immune function and bacterial killing. We need to discuss this in 
-detail because there are widespread misunderstandings about 
-vitamin D among people who are not aware of the true 
-importance of some recent discoveries. 
- 
-There are some researchers that seem to be saying we all need to 
-take more vitamin D and we think this is wrong and this 
-presentation will explain why. 
- 
- 
-I’m going to talk mostly today about the material covered in a 
-book chapter, “High levels of active 1,25D despite low levels of 
-the 25D precursor — implications of dysregulated vitamin D for 
-diagnosis and treatment of chronic disease.” It should be coming 
-out in a month or so. 
- 
-I will present research to back our view that Vitamin D 
-dysregulation due to Th1 inflammation is widespread and is a 
-result of macrophages becoming infected with cell wall deficient or 
-CWD forms of bacteria. I will present evidence and arguments to 
-counter many of the studies behind the push for increasing vitamin 
-D in certain diseases and show the potential harm from excess 
-vitamin D. I will also discuss the controversy over different views of 
-Vitamin D and some very new molecular modeling results. 
- 
-I won’t have time for questions at the end of the talk, but you can 
-ask me questions afterwards individually or email me at 
-jcw@autoimmunityresearch.org. By the way, you should all have 
-handouts of the slides to make it a little easier. 
- 
- 
-Now, I’ll briefly go into some background information in simplified 
-form. In our view, the key to Th1 disease is bacteria-infected 
-macrophages leading to excessive inflammation and increased 
-1,25D production. Th1 cells, a type of T helper lymphocyte, or 
-immune cell, produce the cytokine Interferon Gamma and 
-promote cell mediated inflammation. 
- 
-Th1 cells can stimulate macrophage activity and these activated 
-macrophages also produce Interferon Gamma. The macrophages 
-are supposed to surround and internalize the bacteria in order to 
-destroy them, a process called phagocytosis. 
- 
-Our understanding of Th1 disease is that the macrophages are 
-unable to destroy the CWD bacteria during phagocytosis and 
-instead the bacteria actually thrive inside the very macrophages 
-that are supposed to kill them, leading to chronic disease. 
-Although elevated Interferon Gamma can indicate Th1 disease, it 
-stays mainly in the tissue, and only circulates in the blood to a 
-limited degree. However, the 1,25D produced by the activated 
-macrophages,​ can be more easily detected in the blood than 
-Interferon Gamma. Thus, 1,25D, can serve as a useful marker or 
-indicator of Th1 disease and that is why we measure it, along with 
-25D. 
- 
- 
-Now, on to vitamin D regulation. 
- 
-This first part of the slide shows a simplified view of the vitamin D 
-situation in a healthy person. The precursor form of vitamin D, 
-25D, is the form that most healthy people derive from the diet, 
-supplements and sun exposure. By the way, this shows the situation 
-without the inflammatory cytokines that cause the 25D from the 
-sun to convert directly to 1,25D in the skin. 
- 
-The main point to emphasize here, is that in healthy people, the 
-kidneys tightly regulate the conversion of 25D to keep the 1,25D 
-active steroid hormone in a fairly narrow range. There are parts of 
-other molecules shown here — the vitamin D receptor around 
-here, but this is the vitamin D part. 
- 
-But the only difference is where you add the hydroxyl group, which 
-is this little red oxygen. It’s actually an OH and this is added and it 
-makes all the difference. And here we have a nice picture of a 
-kidney. O.K. So we have the molecule is transformed by adding 
-the hydroxyl group so it can now activate the vitamin D receptor. 
-Most doctors rely on the 25D precursor to decide how much 
-vitamin D is needed, without paying enough attention to the active 
-hormonal form. This only makes sense if one assumes 1,25D 
-levels are regulated by the kidneys with the aid of parathyroid 
-hormone. 
- 
-O.K., Now for the vitamin D dysregulation. Dysregulation is 
-caused by activated macrophages,​ which can convert 25D to 
- 
-1,25D without the kidneys, at a high rate — there you can see the 
-macrophage. 
- 
-So, the macrophages are the source of vitamin D 
-dysregulation in Th1 diseases, aka vitamin D hypersensitivity. 
-This extrarenal, meaning outside of the kidneys, production is well- 
-known in sarcoidosis and other diseases where aggregations of 
-macrophages form granulomas. And as I said before, in Th1 
-disease, the 25D from the sun goes immediately to 1,25D in the 
-skin. 
- 
- 
-Now, you might ask, how does Vitamin D regulation break down? 
-Normally, there are feedback controls that would compensate for 
-overproduction. 
- 
-Well, it turns out we know the enzymes and cytokines involved in 
-this failure to compensate for the macrophage’s production of 
-1,25D. 
- 
-Activated macrophages contain the enzyme 1 alpha hydroxylase 
-that causes the conversion of 25D to 1,25D. Abundant Interferon 
-Gamma, an inflammatory cytokine, can suppress the normal 
-feedback inhibition of 1 alpha hydroxylase that would otherwise 
-help regulate 1,25D production. The Interferon Gamma in the 
-region of inflamed tissue inhibits the enzyme 24-hydroxylase,​ 
-which is involved in 1,25D inactivation. 
- 
-This effect of Interferon Gamma seems to extend to the kidneys, at 
-least in many granulomatous diseases, like sarcoidosis,​ so that the 
-kidney can not effectively compensate for the unregulated 1,25D 
-production by macrophages. 
- 
-Also, inflammatory cytokines cause increased conversion of 7- 
-dehydrocholesterol into 1,25D in the skin, thus providing 
-additional 1,25D that contributes to dysregulation. 
-And what is the result? Well when 1,25D is severely elevated, high 
-blood calcium levels can occur, which may be quite dangerous. 
-But even when 1,25D is moderately elevated, with normal serum 
-calcium levels, bone loss and a wide range of negative 
-consequences may occur. 
- 
- 
-Now, we’ll briefly cover some issues relating to measurement. We 
-think many labs reference ranges are inaccurate because they 
-include undiagnosed Th1 disease patients in their control 
-populations. 
- 
-For this reason, we prefer Merck Manual’s upper limit of 45 pg/ml 
-for 1,25D, to the higher upper limits some labs use. 
-Blood serum for 1,25D tests should be frozen since 1,25D 
-degrades easily. The largest U.S. lab does it this way. 
-In D dysregulation,​ the 25D may become depleted through 
-conversion to the active hormone. So 25D may be low while 
- 
- 
-1,25D may be high, thus one can see the need to measure both. 
-Low 25D, high 1,25D and/or a higher ratio of 1,25D to 25D, 
-known as the D ratio, can be used as an indicator of the level of 
-Th1 inflammation. The D-ratio from a large control population 
-that we use as “normal” is 1.3. 
- 
-The FDA recommends measuring both types of vitamin D 
-when evaluating osteoporosis treatments. We think both 
-tests should also be much more widely done in chronic 
-disease. 
- 
-Now, I am going to review literature that supports our view that D 
-dysregulation due to activated macrophages is actually 
-widespread in inflammatory diseases. 
- 
-In most of these diseases there is also some evidence of bacterial 
-involvement and/or responsiveness to antibiotics. The first example 
-is Inflammatory Bowel Diseases. 
- 
-Abreu et al found 1,25D levels were elevated above 60 pg/ml in 
-40% of Crohn’s Disease and 7% of Ulcerative Colitis patients. The 
-elevated 1,25D was related to reduced bone mineral density that 
-was independent of glucocorticoid use. They also found elevated 
-levels of 1 alpha hydroxylase from colonic biopsies of Crohn’s 
-patients, indicating extrarenal synthesis, as in sarcoidosis. 
-The percentages are much higher if the Merck Manual cutoff for 
-elevated 1,25D, of 45 pg/ml is used — 68% for Crohn’s and 45% 
-for Ulcerative colitis. 
- 
-Now, I will discuss a key experiment supporting extrarenal synthesis 
-of 1,25D in rheumatoid arthritis. 
- 
-Mawer et al challenged 19 RA patients with a large dose of the 
-precursor, 25D, and found that patients generated peak serum 
-levels of 1,25D significantly higher than controls. 
- 
-The 1,25D levels were particularly elevated in the joint fluid in 
-patients. This provides strong evidence for extrarenal synthesis of 
-1,25D in patients with RA. 
- 
-Another important point is that the median serum 1,25D at 
-baseline was not elevated in the RA patients — only 24 pg/ml. 
-Thus the extrarenal synthesis of 1,25D was not obvious from the 
-routine blood test. 
- 
-So, although we do find Vitamin D tests helpful in diagnosis, this 
-study shows that they are not always enough. One may need to 
-look deeper to detect extrarenal synthesis in Th1 disease. 
-It is also the reason why a therapeutic probe with the Marshall 
-Protocol may be needed, when the clinical picture suggests Th1 
- 
- 
-disease, but the vitamin D test results are unclear. A therapeutic 
-trial is when one uses the MP, and assess symptom changes — like 
-bacterial die off reactions — to determine if the protocol is 
-appropriate. 
- 
- 
-Some additional independent studies in RA are also relevant here. 
-In vitro studies of macrophages from synovial fluid or joint fluid in 
-RA also revealed synthesis of 1,25D and elevated D-ratios. Inaba 
-found elevated 1,25D to be related to elevation of IL-1 and IL-2. 
-These 2 inflammatory cytokines are correlated with disease activity. 
-IL-1 has also been implicated in increased bone loss. 
-Sambrook et al found little, if any bone loss near the wrist joint in 
-patients with RA with the lowest 1,25D. Those with higher 1,25D 
-had significant bone loss near their wrist joints. 
-In our view, these various findings argue against vitamin D 
-supplementation to prevent inflammatory damage or bone loss in 
-RA. The role of bacteria and antibiotics shown in several studies 
-further support our view that RA is similar to sarcoidosis in its 
-underlying bacterial cause. 
- 
- 
-O.K., as for lupus, two studies measuring vitamin D levels are 
-consistent with Vitamin D dysregulation,​ giving D-ratios of 2.1 and 
-2.2, well above the 1.3 average for the healthy. 
-Interestingly,​ increased lupus mortality has been found to be 
-associated with UVB solar radiation in a correlational study and we 
-believe this effect probably occurs through increasing 1,25D. 
-It is known that lupus patients have flares of symptoms in response 
-to UVB light, and sometimes even to fluorescent or UVA light, 
-something we observe in sarcoidosis. There was at least one study 
-that seems to support the role of bacteria. From all of this, we 
-conclude lupus (SLE) is a Th1 disease. 
- 
- 
-Only one study in fibromyalgia measured both vitamin D forms 
-and the D ratio was elevated at 1.7. 
- 
-Several other studies showed a tendency to low levels of 25D in 
-these several chronic pain and fatigue states and this is consistent 
-with our hypothesis of extrarenal conversion by activated 
-macrophages depleting 25D. 
- 
-Several researchers have linked chronic fatigue syndrome and 
-fibromyalgia with bacteria, including Borrelia and Mycoplasma. 
-Now, in Sjogren’s Syndrome, the D-ratio was 2.7 and the study 
-authors mentioned this indicated a disturbed vitamin D 
-metabolism. 
- 
- 
-O.K. Multiple Sclerosis. We have shown some vitamin D patterns 
-and how they relate to our view that bacterial infection causes 
-vitamin D dysregulation. In Multiple sclerosis or MS, vitamin D 
-data is lacking, but there are other types of studies that have been 
-used to try to link MS with a lack of vitamin D. And I will discuss 
-some of the problems we see with these studies. 
-The initial reason for the interest in vitamin D in MS is that a higher 
-rate of disease had been observed in higher latitudes — and it has 
-been claimed that this is due to less sun exposure producing less 
-vitamin D. 
- 
-We will focus on one of the alternative explanations — that the 
-pattern is caused by the geographic distribution of bacterial 
-pathogens not solar radiation. An analysis by Fritzsche related the 
-geographical and seasonal pattern of MS to that of the tick that 
-carries the Lyme spirochete Borrelia burgdorferi. 
- 
-Also, Chlamydiae pneumoniae is known to be more commonly 
-acquired in the winter and this may relate to geographical patterns 
-due to the greater amount of time spent indoors at higher 
-latitudes. Chlamydiae pneumoniae has been linked to progressive 
-MS by Munger et al. 
- 
-Our view is that multiple bacterial pathogens are probably the 
-cause of MS and other Th1 diseases. This seems likely because 
-immune dysregulation initiated by the first pathogen would tend to 
-promote infection with other species. 
- 
-There is also abundant direct evidence for the role of bacteria in 
-MS, for example, see Brorson et al and Mattman. Mattman has 
-some reviews of numerous studies. 
- 
- 
-Some studies have been done linking low vitamin D consumption 
-and serum 25D patterns to a greater rate of MS. One reason we 
-think low 25D might be observed to precede MS is increased 
-conversion of 25D to 1,25D by macrophages thus depleting 25D 
-in early stages of illness prior to being diagnosed — the low 25D 
-is thus not a cause but an early effect of MS. 
- 
-There are other factors that may bias results and you can see the 
-book chapter for some examples. Since we know that correlation 
-does not imply causation, these types of observational studies, by 
-their very nature, can not prove a benefit of Vitamin D in 
-preventing MS. 
- 
-But, if future randomized controlled trials were to show a 
-preventative effect of vitamin D for MS, this might be due to 
-enhancement of immune response to the initial phase of bacterial 
-infection through correction of very low levels of vitamin D in 
-certain individuals. There is some limited evidence for this in 
-Tuberculosis. But even if this preventative effect were proven, this 
-would not mean vitamin D supplementation would be beneficial in 
-patients already ill with MS, since, in our view, increased 1,25D 
-synthesis would be occurring once the illness is established. 
- 
- 
- 
-Another type of study that has been done in MS involves short term 
-experiments in which some form of vitamin D is given. 
-Several studies have shown a benefit from elevated 1,25D in 
-prevention and treatment of experimental allergic 
-encephalomyelitis,​ EAE, in mice. This is an animal model used to 
-try to approximate MS. 
- 
-Some of the pitfalls of studies of this type include differences in the 
-physiology of humans and mice and the short time span of the 
-experiment. There is also likely to be different disease causation 
-involved in EAE. Even if a given animal model, such as this one, 
-did apply to human MS, giving large amounts of 1,25D might be 
-able to halt the disease process in EAE only due to 
-immunosuppression. But the short time span of the experiment 
-would fail to detect a long-term worsening that might occur due to 
-bacterial increase occurring as a result of the immunosuppression. 
-Likewise, in studies in humans with MS, we view the short term 
-nature of the few studies that have been done as the likely reason 
-that benefit has sometimes been linked to vitamin D. 
- 
- 
-Now, I will discuss some new research on the mechanisms by 
-which we think too much of either form of Vitamin D may suppress 
-bacterial killing and harm long term health in Th1 disease. 
-Recent molecular modeling research indicates that high 25D levels 
-block innate immunity. Sophisticated computer modeling of the 
-molecules shows that the 1-alpha-hydroxy position is key to 
-activation of the Vitamin D Receptor or VDR. 25D can bind to the 
-VDR, but since it lacks the 1-alpha-hydroxy found in 1,25D, it will 
-bind to the VDR but fail to activate it. 
-The affinity constants show that 25D above approximately 20 
-ng/ml can thus displace 1,25D, blocking VDR (Vitamin D 
-Receptor) activation and thus blocking innate immunity. This is 
-supported by our finding that bacterial killing increases for patients 
-on the Marshall Protocol when 25D goes below 20 to 25 ng/ml. 
- 
- 
-As for 1,25D, although it aids the immune response by stimulating 
-the vitamin D receptor, too much 1,25D suppresses the immune 
-system, inhibits bacterial killing and causes hormonal disruption. 
-New evidence indicates these negative effects of high 1,25D do 
-not occur through its binding to the VDR, but through its excessive 
-binding to thyroid, glucocorticoid and other receptors. Dr. 
-Marshall has recently presented molecular modeling evidence for 
-this at an FDA Visiting Professor presentation. 
- 
-If, as we believe, a bacterial cause underlies these Th1 diseases, 
-then immunosuppression from high 1,25D is harmful in the long 
- 
- 
-O.K. Theses are not real portraits of the people — so, you don’t 
-need to go around looking for the silhouettes to match it. 
-Most of the data collected on hundreds of patients — prior to 
-starting the MP — is fitting the pattern of vitamin D dysregulation 
-that we described above, indicating increased production of 
-1,25D by macrophages. Dr. Marshall presented slides of some of 
-this data on sarcoidosis,​ RA, Lyme, CFS and fibromyalgia at the 
-Chicago Conference and elsewhere. 
- 
-Today, I will just talk briefly about 4 of the 12 patients we discuss in 
-the book chapter to illustrate the pattern of vitamin D values in a 
-variety of illnesses. 
- 
-In some cases, the 25D is somewhat elevated. Usually this is due 
-to vitamin D in food or supplements,​ and it tends to bias the D- 
-ratio downward. Patient 9 has MS, diagnosed 9 years ago. One 
-can see her 1,25D of 53 is above the Merck upper limit and her 
-25D is rather high at 35 ng/ml and her ratio is a little elevated at 
-1.5. She has a history of worsening on daily doses of 2000-4000 
-IU vitamin D. And one symptom that had worsened while on the 
-vitamin D improved after stopping it prior to the Marshall Protocol. 
-Patient 10 has amyotrophic lateral sclerosis or ALS. He has an 
-elevated 1,25D of 58.9, a 25D of 36 ng/ml and a D ratio of 1.6. 
-Both patients 9 & 10 have had bacterial die-off reactions, also 
-called Jarisch Herxheimer reactions, as expected on the Marshall 
-Protocol, but it is too soon to know if they have improved. 
-Patient 11 has rheumatoid arthritis and had an initial 1,25D of 65, 
-25D of 32, and a D ratio of 2. During 2 years on vitamin D 
-supplementation prior to the Marshall Protocol, her condition 
-worsened. Also, she failed to improve during several years on an 
-antibiotic-only protocol, but improved significantly on the Marshall 
-Protocol in less than 18 months. 
- 
-Patient 12 has been disabled for 20 years by chronic fatigue 
-syndrome, fibromyalgia and Lyme disease. With her 1,25D at 64 
-and her 25D at only 11, giving a ratio of 5.8, this patient is a 
-good example of 25D being depleted by conversion to 1,25D. 
-Sun exposure elevates her heart rate and worsens a number of 
-other symptoms. She has improved considerably on the MP. 
- 
- 
-O.K., as to the controversy on vitamin D. Why do some advocate 
-taking so much vitamin D and why do we think they are wrong? 
-To begin with, many vitamin D advocates focus on the issue of 
-secondary hyperparathyroidism,​ which occurs when serum calcium 
-is low, causing parathyroid hormone to increase, which can lead 
-to bone resorption and osteoporosis. The hyperparathyroidism 
-leads to a greater production of 1,25D by the kidneys, to try to 
-compensate for the low calcium. 
- 
- 
-This is why some researchers think it wrong to look at 1,25D levels 
-when considering whether a patient is deficient in vitamin D. Their 
-claim is that the 1,25D is meaningless,​ since it may be 
-compensating for a low 25D. 
- 
-Of course, we agree that secondary hyperparathyroidism certainly 
-can lead to bone loss. However, in several Th1 diseases we have 
-discussed, sarcoidosis,​ RA and Inflammatory Bowel Disease, any 
-hyperparathyroidism was specifically ruled out as an explanation 
-for the patterns. Rather, the Vitamin D results were clearly related 
-to inflammation. We think that evidence points to inflammation as 
-the explanation of the vitamin D patterns in the other Th1 diseases, 
-as well. 
- 
-To clarify a little further, secondary hyperparathyroidism occurs in 
-order to compensate for low calcium, not low 25D. The 1,25D 
-can increase the percentage of calcium absorbed, but is not even 
-necessary for its absorption, since when calcium is adequate, most 
-of the absorption is passive. 
- 
-The role of calcium is shown in a study of patients who had 
-abundant calcium in their diet, and it was found that only 7% of 
-the variation in parathyroid levels was related to 25D. And there 
-was no link between bone mineral density and 25D. It turns out 
-that calcium intake below the recommended level is widespread 
-according to the NIH, varying from 44% to 87% depending on sex 
-and age. 
- 
-And in our view providing adequate calcium is a safer way to 
-avoid secondary hyperparathyroidism than vitamin D 
-supplementation. MP patients maintain bone health by first 
-avoiding elevated 1,25D that stimulates bone loss through 
-osteoclast activity and by having adequate calcium and just 
-generally keeping 1,25D in the normal range. We have observed 
-no problems from even quite low 25D levels among MP patients. 
- 
-Another area that needs to be clarified is the question of whether 
-extrarenal production of 1,25D is good or bad. The answer is it 
-depends on how much and what is the source. 
- 
-There is now a theory that a lot of extrarenal production of 1,25D 
-in many tissues is important and must be fueled with a large level 
-of 25D. Now there are normally low levels of 1,25D production by 
-many types of cells and that is fine and normal. But we have been 
-referring to something different — to the excessive production of 
-1,25D by macrophages in a Th1 disease. 
- 
-Well, some say that even this increased 1,25D production by 
-macrophages is good — that it is an attempt to protect the body 
-from too much inflammation by suppressing the immune system. 
-But, we think this idea falls apart if we are dealing with a chronic 
-infection. We have presented evidence for several ways in which 
-high 25D and 1,25D can negatively affect the immune system’s 
-ability to fight CWD bacteria and thus lead to long term harm. 
- 
- 
-The success of the MP in treating patients is further evidence for 
-our view, since lowering vitamin D has been found to be beneficial 
-for bacterial killing. 
- 
-Some vitamin D proponents believe that very high levels of vitamin 
-D are needed, levels that may exceed those found to cause harm 
-in some studies. How could it be that some seem to find a benefit? 
-In the light of what we know, it makes the most sense to us that the 
-reason they find a need for high intakes of vitamin D are two fold. 
-They may be unwittingly be relying on the immunosuppressive or 
-anti-inflammatory effect of high 25D, which may temporarily 
-correct problems with kidney, parathyroid function, or other 
-problems that are really associated with bacteria-induced 
-inflammation. The high 25D they achieve suppresses the bacterial 
-killing and associated die off reactions and may cause some short 
-term benefit, but long term harm. This explanation may even apply 
-to some elderly patients who seem to have improved muscle 
-strength when given vitamin D. 
-Another reason some vitamin D advocates may find they require 
-such high vitamin D intakes is that conversion to 1,25D by 
-macrophages continually depletes the 25D in Th1 disease, making 
-it harder to keep serum levels of 25D as high as they want them. 
- 
- 
-As for future research directions, there is a need for more data on 
-25D and 1,25D levels. 
- 
-But, as we have shown, the role of 1,25D production by 
-macrophages is not always obvious from simple blood tests. In the 
-less clear cut cases, as in rheumatoid arthritis, 1,25D elevation 
-may be at a lower level and more restricted to areas of inflamed 
-tissue and thus not show up in the blood test. 
-Despite our belief that the response so far to the MP is strong 
-enough to warrant immediate trials for many diseases, further 
-experiments on vitamin D might be useful. Experiments could be 
-done to detect increased synthesis of 1,25D by macrophages by 
-challenging with a dose of 25D and comparing responses with 
-controls — and then looking at levels of 25D and 1,25D in 
-inflamed tissues and so on, like the experiments discussed earlier 
-in RA. 
- 
- 
-What other diseases might be good candidates for this type of 
-investigation?​ The answer is, basically, any chronic disease with 
-unknown cause. 
- 
-But especially diseases where some link to vitamin D has been 
-found — either a positive or negative effect, since this might be a 
-sign of increased synthesis of 1,25D by macrophages. 
- 
- 
-Examples of some of the diseases that might have Vitamin D 
-dysregulation include: heart disease and stroke; psychiatric 
-illnesses, like bipolar, depression and schizophrenia;​ Parkinson’s 
-Disease; Alzheimer’s;​ autism and cancer. 
- 
-Listed on the slide are studies that find evidence suggesting a role 
-for bacterial pathogens or a beneficial effect of antibiotics or 
-suggestions of vitamin D having a positive or negative effect. 
-I should mention that there has been research, mostly 
-observational studies, that support a positive role for Vitamin D in 
-cancer prevention. We think many of the problems with these types 
-of studies in cancer are similar to the problems we discussed in the 
-section on MS. And one must also be careful to distinguish the 
-effects of calcium from that of vitamin D and oftentimes it’s not 
-clear whether it’s the calcium. 
- 
- 
-Cancer Treatment and Progression in Relation to Vitamin D 
-With regard to cancer treatment, there are many studies 
-supporting 1,25D’s anti-tumor effects. But for this effect to be 
-useful in treatment, the 1,25D must be at high levels that produce 
-a high risk of side effects. Neither 1,25D, nor any of the synthetic 
-analogs created to mimic it, has yet been approved to treat 
-cancer. The Mayo clinic, on their web site, concludes the data on 
-vitamin D’s role in cancer is still unclear. 
- 
-We have seen no evidence for an increase in cancer rates in 
-patients on the MP who have lowered their vitamin D levels. 
-Research discussed above, shows high 1,25D may be reducing the 
-killing of intracellular bacteria. If bacteria, and the inflammation 
-that accompanies the bacterial infection, are the underlying cause 
-of a cancer, then we think effectively treating the bacteria may 
-outweigh any anti-tumor effect of increasing 1,25D. 
- 
-And as was mentioned, H. pylori has been linked to ulcers, but it’s 
-also been linked to stomach cancer. So there is a clear example 
-where the bacteria is the carcinogen. 
- 
- 
-There is some interesting work on breast cancer and Vitamin D 
-that may suggest bacterial involvement. There was a study that 
-found a tendency for 1,25D to become very low in late stage 
-breast cancer. In a possibly parallel situation, in some of the very 
-sickest patients with a very high bacterial load, 1,25D has become 
-quite low through an unknown mechanism. 
-In tuberculosis,​ Palmieri found this and in some Th1 patients, Dr. 
-Blaney has found this also — this very low 1,25D also. But then, 
-remarkably, the 1,25D increased with appropriate antibacterial 
-treatment. 
-This may suggest that the progression of a bacterial infection to a 
-very severe level could account for the very low 1,25D in late 
-stage breast cancer and thus bacteria could be the underlying 
-cause of the cancer. Perhaps effective antibiotic treatment for CWD 
-bacteria could reverse the process in breast cancer and restore the 
-1,25D levels as it did in the tuberculosis and the very sick Th1 
-patients I just mentioned. 
- 
- 
-As you know from what I have said before, the 1,25D is usually 
-elevated in Th1 disease. So it is interesting that some of the early 
-breast cancer patients had an unexplained elevation in 1,25D, 
-which may reflect the more typical situation of a Th1 disease 
-before bacterial loads become too extreme and 1,25D drops. 
- 
- 
-A recent article showed breast cancer rates correlate with more 
-frequent antibiotic use. We think this may suggest a bacterial 
-cause for breast cancer. 
- 
-In our view, antibiotic use can be thought of as reflecting the 
-susceptibility to and frequency of bacterial infections. Many species 
-of bacteria have been shown to be able to transform into cell wall 
-deficient forms when under attack in order to escape destruction. 
-CWD bacteria are resistant to antibiotics in the usual ways they are 
-used, so taking antibiotics will not generally eliminate them. And 
-treatment with the most commonly used antibiotics even promotes 
-the transformation of bacteria into their CWD forms, which can 
-then persist inside the body inside macrophages and other cells 
-and increase over time. 
- 
-Thus, in our interpretation,​ the more exposure to bacteria 
-indicated by the greater antibiotic use in the study, the more 
-opportunities for the creation of CWD bacterial forms, which may 
-then lead to Th1 disease and possibly to cancer. 
- 
-A particularly interesting,​ large new study on vitamin D and 
-prostate cancer went beyond the geographical correlational 
-studies and actually measured the 25D levels. They found that the 
-highest rates of cancer occurred when serum 25D was low (<8 
-ng/ml) and when it was high (>33 ng/ml), giving a U shaped 
-curve. 
- 
-We think these patterns may indicate Th1 disease due to bacteria. 
-Here is our hypothesis to explain this pattern. The low 25D link to 
-cancer, rather than indicating a deficiency, could be a sign of 
-depletion of 25D through conversion to 1,25D. Thus, it may be 
-simply a marker for a Th1 process. As we have discussed, the 
-resulting high 1,25D in Th1 disease suppresses the immune 
-system’s ability to fight bacteria and thus may help lead to cancer. 
- 
-On the other hand, a very high level of 25D could help cause a 
-higher rate of cancer due to the high 25D suppressing the immune 
-system, as previously discussed. The result would then be that 
-innate immunity is less functional and less able to combat 
-bacteria, which may then lead to cancer. 
- 
-The lowest cancer rate was in the middle region, 16-24 ng/ml, 
-where the above two factors are least prominent. But it should be 
-emphasized, that we do not think this data shows that the optimal 
-level of 25D is in the middle region. In our view, the low 25D is 
-linked to cancer merely because it is a marker of Th1 disease, not 
-a causal factor. 
- 
-The authors of the prostate cancer study concluded that too high a 
-level of 25D might increase the risk of prostate cancer. As you saw from our patients slide, it isn’t that hard to exceed 30 ng/ml of 
-25D, especially with vitamin D supplements — 3 of the 4 patients 
-had levels above 30. 
- 
-In conclusion, we have shown that Vitamin D dysregulation may 
-produce patterns of elevated 1,25D, depleted 25D or an elevated 
-D-ratio, as we show for a variety of chronic Th1 diseases. 
-Elevated 25D or 1,25D might make the patient feel better or 
-worse in the short run, but in either case, make them worse in the 
-long run. This worsening occurs through immunosuppression 
-promoting bacterial increase. 
- 
-We think the evidence for this new view of vitamin D 
-requires re-evaluation of many previous studies and calls for 
-new types of studies in many chronic diseases. 
- 
-Although usually quite helpful, Vitamin D blood tests do not always 
-accurately reveal Th1 disease. Thus, if the clinical picture suggests 
-Th1 disease, we find a therapeutic probe using the Marshall 
-Protocol as the “gold standard” test for Th1 disease and bacterial 
-involvement. 
- 
-If you think about it, it seems little wonder that vitamin D has 
-become so popular. It’s basically an over-the-counter steroid — 
-but its effects are more subtle and insidious than something like 
-prednisone since it blocks only innate immunity, leaving adaptive 
-immunity intact. 
- 
-We think that further study of vitamin D dysregulation appears 
-likely to provide a window onto the immune system, improving 
-diagnosis and treatment for many chronic diseases. 
-Thank you for your attention. 
- 
-{{tag>​presentations 2006 videos Joyce_Waterhouse_PhD}} 
  
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