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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
+,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
+D.
+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,
+D, 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 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
+,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
+,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
+,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
+% 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
+,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, 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
+,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
+D is rather high at 35 ng/ml and her ratio is a little elevated at
+.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,
+D 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
+,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
+D 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
+,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
+D, 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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