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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
 +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 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
 +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
 +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
 +Now, you might ask, how does Vitamin D regulation break down?
 +Normally, there are feedback controls that would compensate for
 +Well, it turns out we know the enzymes and cytokines involved in
 +this failure to compensate for the macrophage’s production of
 +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
 +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
 +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
 +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
 +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
 +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
 +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
 +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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