wpływ wit D na panel hormonalny.

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Witamina D jest podzielona na dwa rodzaje D 1,25 OH jest to hormon który powinien być w średniej wartości normy jak jest wysoki to zaburza inne hormony LH test, gonadotropowy, jądra, TSH, receptory insulinowe, jest odpowiedzialny za skórę, za kości, włosy może powodować osteoporozę. Wynikiem jego wysokiego poziomu jest obniżenie zawartości wit D 25 OH w organizmie i skutkiem tego wszystkie te powyższe niedomogi.
Sorry za słaby wygląd rysunku ale musiałem go zmniejszyć i tak wyszło

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Nikt nie zwraca na to uwagi, a nie dobrze. Wit d i jej poziom jest jednym z największych rzeczy na które powinnismy uważać. Od dłuższego czasu suplementuje i różnica jest kolosalna w samopoczuciu jak i uodpornieniu na przeziębienia itd. Gruba wiekszosc osób ma niedobór

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ja tez mam niedobór z badania w 2005r wyszło że witaminy d 025oh mam zaledwie 9 a hormonu d1,25oh wysoko ponad norme ktora jest do 40 a ja miałem 68.

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Science behind vitamin D
A number of studies have suggested that patients with chronic inflammatory diseases are deficient in 25-hydroxyvitamin D (25-D (http://mpkb.org/home/tests/25d)) and that consuming greater quantities of vitamin D, which further elevates 25-D levels, alleviates disease symptoms.
Some years ago, molecular biology identified 25-D as a secosteroid. Secosteroids would typically be expected to depress inflammation, which is in line with the reports of short-term symptomatic improvement. The simplistic first-order mass-action model used to guide the early vitamin studies is now giving way to a more complex description of action.
When active, the Vitamin D nuclear receptor (http://mpkb.org/home/pathogenesis/innate_immunity#role_of_vitamin_d_receptor_in_inna te_immunity) (VDR) affects transcription of at least 913 genes and impacts processes ranging from calcium metabolism to expression of key antimicrobial peptides (http://mpkb.org/home/pathogenesis/innate_immunity#antimicrobial_peptides). Additionally, recent research on the Human Microbiome shows that bacteria are far more pervasive than previously thought, dramatically increasing the possibility that the spectrum of chronic diseases is bacterial in origin.
Emerging molecular evidence suggests that symptomatic improvements among those administered vitamin D is the result of 25-D’s ability to temper bacterial-induced inflammation by slowing VDR activity. While this results in short-term palliation, persistent pathogens that influence disease progression proliferate over the long-term.
Forms and structure of vitamin D
Main article: Forms and structure of vitamin D (http://mpkb.org/home/pathogenesis/vitamind/forms)
All forms of vitamin D are secosteroids, sharing a close structural and functional resemblance to steroids. The full implications of a “vitamin” acting as a steroid has yet to be fully appreciated by many in the research community. The overlap between steroids and secosteroids is key to understanding the Marshall Pathogenesis (http://mpkb.org/home/pathogenesis). It explains how a “vitamin” can exert short-term palliative effects and long-term harm. Patients on the MP are advised to avoid consuming vitamin D, because of its immunomodulatory effects.
Steps for synthesis of vitamin D
There are a number of vitamin D metabolites in the body. The steps by which one form of vitamin D changes into the next are as follows:


The body has natural stores of 7-dehydrocholesterol (http://mpkb.org/home/pathogenesis/vitamind/forms), a cholesterol (http://mpkb.org/home/tests/lipids) precursor.
When exposed to energy, specifically ultraviolet light, 7-dehydrocholesterol becomes pre-vitamin D3.
Pre-vitamin D3 spontaneously isomerizes to Vitamin D3 via a process called sigmatropic shift.
In addition to the endogenous production of Vitamin D3, people get D3 from animal meats. Vitamin D2 is found in plants and fungi, and is functionally similar to D3.
Vitamin D3 and D2 are hydroxylated in the liver, and becomes 25-hydroxyvitamin D (25-D).
25-D is further hydroxylated by the enzyme 1α-hydroxylase, into the main biologically active hormone 1,25-dihydroxyvitamin D (http://mpkb.org/home/tests/125d) (1,25-D). While this reaction was originally thought to occur only in the kidneys, is now known to take place in tissues throughout the body, including within white blood cells called macrophages.

file:///C:\DOCUME~1\RAFA~1\USTAWI~1\Temp\msohtmlclip1\01\c lip_image001.gif
The foundation of the Marshall Pathogenesis is “Figure 1,” a graphic which appeared in Trevor Marshall's 2008 Bioessay.
It's important to understand that the body tightly regulates the different forms as it might a steroid.
Metabolism of vitamin D and the Vitamin D Receptor in chronic disease
Main article: Metabolism of vitamin D and the Vitamin D Receptor (http://mpkb.org/home/pathogenesis/vitamind/metabolism)
A number of studies have suggested that patients with chronic inflammatory diseases are deficient in 25-hydroxyvitamin-D (http://mpkb.org/home/tests/25d) (25-D) and that consuming greater quantities of vitamin D, which elevates 25-D levels, alleviates symptoms of disease. Some years ago, molecular biology identified 25-D as a secosteroid. Secosteroids would typically be expected to depress inflammation (http://mpkb.org/home/pathogenesis/innate_immunity#inflammation), which is in line with the reports of symptomatic improvement. The simplistic first-order mass-action model used to guide the early vitamin studies has given way to a more complex description of action. When active, the Vitamin D nuclear receptor (http://mpkb.org/home/pathogenesis/innate_immunity#role_of_vitamin_d_receptor_in_inna te_immunity) (VDR) affects transcription of at least 913 genes and impacts processes ranging from calcium metabolism to expression of key antimicrobial peptides (http://mpkb.org/home/pathogenesis/innate_immunity#antimicrobial_peptides).
Located in the nucleus of a variety of cells including immune cells, the VDR is a control system of sorts. When exposed to infection and damage, especially that which is caused by pathogens, the body begins to convert the inactive form 25-D into the active form, 1,25-D (http://mpkb.org/home/tests/125d). As cellular concentrations of 1,25-D increase, 1,25-D activates the VDR, turning on any number of genes the receptor transcribes.
According to a 2010 analysis, the VDR significantly affects 229 human genes. Many of these genes have long been associated with autoimmune diseases (http://mpkb.org/home/alternate/autoimmunity) and cancers (http://mpkb.org/home/diseases/cancer) including, for example, the genes IRF8 (linked to multiple sclerosis (http://mpkb.org/)), and PTPN2 (connected to Crohn's disease (http://mpkb.org/home/diseases/ibd) and type I diabetes (http://mpkb.org/home/diseases/diabetes1)).1 (http://mpkb.org/home/pathogenesis/vitamind#fn__1) The activation of certain genes also leads to the synthesis of

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antimicrobial peptides. The antimicrobial peptides are the body's “natural antibiotics” and have a potent anti-bacterial effect.
However, bacteria create ligands, which like 25-D, inactivate the VDR and, in turn, the innate immune response. This allows the microbes to proliferate. In response, the body increases production of 1,25-D from 25-D, leading to one of the hallmarks of chronic inflammatory disease: a low 25-D and a high 1,25-D.
This pattern is a result of the disease process rather than a cause. For a variety of reasons, neither increased consumption of vitamin D nor the body's synthesis of additional 1,25-D is ultimately effective at combatting infection.
Supplemental vitamin D tends to be immunosuppressive
Related section: Sunlight can be immunosuppressive
Supplemental vitamin D has been widely lauded for conferring immunosuppressive effects.
Vitamin D affects the immune system at many levels and by a number of mechanisms…. Vitamin D has multiple immunosuppressant properties…. On the whole, vitamin D confers an immunosuppressive effect.
Aronson, Amital, and Shoenfeld 2
Supplemental vitamin D is being touted as having a wide range of benefits in different diseases. A puzzling picture that emerges from the totality of the diseases that they are claimed to affect beneficially, is the belief that supplemental vitamin D will both reduce infections and suppress the immune system at the same time. While it is clear that there exist substances that can be “immunomodulating”, implicating that it can increase production/release of both immunosuppressive and immune activating substances, the important question is what the overall effect is. It is hard to envision that a substance can have strong anti-infectious properties while at the same time having a strong immune suppressive effect.
Supplemental vitamin D show no consistent effects on infection
In studies on acute respiratory tract infection3, tuberculosis4 and overall infections5, the effects of vitamin D have been mixed (and largely unsuccessful) in terms of reducing infectious burden.
A complete evaluation of the above mentioned studies, and the differences between them that can help explain the different results, is not suited for this article. However, on a general basis, one of the reasons for differing effects may be that vitamin D works differently in relatively healthy people as compared to sick people. Thus, vitamin D supplementation may give a marginal benefit in preventing infections in healthy people (see section below), but not in sick people. As of today (Dec 2012) we are not aware of any studies that have shown an actual reduction in infections in sick people (for instance tuberculosis or COPD) by vitamin D supplementation, as measured by culture or genetical detection methods. Furthermore, a general trend seems to be that apparent beneficial effects on infection in healthy people are not seen in individuals who have 25-hydroxyvitamin D levels within the normal range678, adding, as a side point, further weight to the mega dose vitamin D supplementation craze being without merit.
It is however not certain, in spite of some reported benefits in a few studies, that any level of supplementation is beneficial in terms of reducing infection. The studies are still too few to draw firm conclusions, and publication bias, as in any field science, may skew the overall results. Another factor which makes the reported benefits doubtful is that not all studies have reported an actual reduction in infection, but merely symptom based outcomes. Symptom based outcomes are relevant, but in light of the symptom reducing effects therapies that are immune suppressive may have, it is not clear that symptom reduction in the vitamin D supplementation studies are due to an actual reduction in infection. Further, most of the symptoms in upper respiratory tract infections are caused by the body's own immune response, and not the infectious agents9.
In sick people vitamin D supplementation increases infectious burden, and suppresses the immune system:
• monocytes – According to a 2011 interventional study in which patients with multiple sclerosis were given high doses of vitamin , peripheral blood mononuclear cells (monocytes) lose “abnormal reactivity” at 40 ng/mL.10
• Epstein Barr virus – In a 2010 study of pregnancy-associated breast cancer, higher levels of 25-D were positively correlated with serum antibodies to Epstein Barr Virus, suggesting that EBV is able to better proliferate in patients who take vitamin D.11
• toll-like receptors – As discussed elsewhere, the toll-like receptors (TLR) represent an ancient front-line defense system that enables the host organism to sense the presence of microbial components within minutes. As inducers of inflammation, TLRs act as important triggers of distinct entities such as sepsis or autoimmune disease exacerbation.12 For example, found that the TLRs are naturally upregulated in the autoimmune disease, Behcet's disease.13 However, a 2006 study showed that vitamin D3 suppresses the expression of TLR2 and TLR4 protein and mRNA in human monocytes in a time- and dose-dependent fashion.14 Dickie et al. further showed that expression of TLR9 was downregulated in monocytes by vitamin D3 supplementation.15
• reduction in levels of inflammation – A 2011 study showed that in colorectal adenoma patients, the vitamin D supplementation group, TNF-alpha decreased 13%, IL-6 32%, IL-1 beta 50%, and IL-8 15% relative to placebo.16
• short-term symptom resolution – Further evidence for vitamin D’s activity as an immunosuppressant comes in the range of reports of short-term symptom resolution in autoimmune patients taking vitamin D. Online forums are full of such reports.
Role in select diseases and conditions
The following articles discuss the role of vitamin D in select diseases. A more complete list of diseases that have been shown to have low level of 25-D is also available.
Osteoporosis
Main article: Osteoporosis and osteopenia

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Both osteoporosis (http://mpkb.org/home/diseases/osteoporosis_osteopenia) and osteopenia are diseases marked by a decrease in bone mineral density. Osteopenia is a less severe form of and sometimes precursor to osteoporosis. The loss of bone mass leads to a porous bone structure, frequent fractures, and delayed healing.
Among doctors, and even many researchers, it is conventional wisdom that vitamin D supplementation reverses osteopenia and osteoporosis. However, a growing body of interventional trials and molecular evidence shows this is not the case. Instead, current research has demonstrated that osteoporosis and osteopenia are often the direct result of infection with the Th1 pathogens (http://mpkb.org/home/pathogenesis/microbiota), a metagenomic microbiota (http://mpkb.org/home/pathogenesis/microbiota), which produce inflammatory cytokines (http://mpkb.org/home/pathogenesis/innate_immunity#inflammation) and inactivate the Vitamin D Receptor (http://mpkb.org/home/pathogenesis/innate_immunity#role_of_vitamin_d_receptor_in_inna te_immunity). The only way to achieve long-term reversal of bone loss is to kill the Th1 pathogens driving the disease process.
Rickets
Main article: Rickets (osteomalacia) (http://mpkb.org/home/diseases/rickets)
Rickets (osteomalacia) is a softening of the bones that leads to fractures and deformity. The majority of cases of rickets occur among children in developing countries who suffer from severe malnutrition. The disease is cited as a primary reason for consuming vitamin D (http://mpkb.org/home/pathogenesis/vitamind) regularly even though research has demonstrated that rickets is not caused by vitamin D deficiency but by hypophosphatemia.
The latest molecular evidence does not support adding high levels of vitamin D to the food chain in the name of “preventing rickets.” The health of the public would be much better served by regulations ensuring that they obtain adequate calcium and phosphorous rather than vitamin D.
Cancer
Main article: Vitamin D and cancer (http://mpkb.org/home/pathogenesis/vitamind/cancer)
A variety of studies have suggested that vitamin D protects against cancer (http://mpkb.org/home/diseases/cancer). This seemingly intuitive proposition is supported by neither epidemiological nor molecular evidence. In fact, the very opposite is true. This article reviews why this body of research is most likely incorrect – or at the very least, much more complicated than articles in the popular media would have a person believe.


Latitude studies (http://mpkb.org/home/pathogenesis/vitamind/latitude) - The “latitude studies” are observational, as opposed to interventional, studies, which use ambient solar UV radiation as a proxy for latitude and vitamin D status. For these studies, researchers compare rates of certain major cancers - most notably breast, colorectal and prostate cancer - to rates of sunlight exposure. This group of research has the liability of being wildly inconsistent. The choice to publish research on a specific latitude gradient may be a better proxy for a researcher's bias.
Interventional studies - While some randomized controlled trials have suggested that consuming vitamin D reduces rates of cancer, larger and more carefully controlled studies show no such effect.
Studies of vitamin D status - Many of the studies examining the relationship between vitamin D status and incidence of cancer argue that low levels of 25-D contribute to cancer. This conclusion has been invalidated by larger well-controlled studies. Although the immune system works to downregulate 25-D (25-hydroxyvitamin D) in inflammatory diseases such as cancer, very high levels of 25-D are a clear indication of regular supplementation. These studies suggest that consuming large amounts of vitamin D predispose a person to increased incidence of cancer.
Observational studies – Some case control studies have found that vitamin D intake seems to increase incidence of certain types of cancer.

According to the Marshall Pathogenesis, alteration of vitamin D metabolism by a pathogenic microbiota (http://mpkb.org/home/pathogenesis/microbiota) prevents any benefit from vitamin D supplementation.
Cardiovascular disease
Main article: Cardiovascular disease (http://mpkb.org/home/diseases/cardiovascular)
According to a 2010 paper by Swales and Wang, “despite substantial clinical evidence linking vitamin D deficiency with increased cardiovascular risk, it remains to be established whether this represents a causal association.”17 (http://mpkb.org/home/pathogenesis/vitamind#fn__17) Indeed, data from a 2011 prospective, randomized, placebo-controlled trial[cite needed]18 (http://mpkb.org/home/pathogenesis/vitamind#fn__18) has cast real doubt on the alleged cardioprotective benefits of vitamin D. Researchers performing a small study report that treatment with vitamin D for four months had no significant effect on endothelial function, vascular stiffness, or inflammation in healthy postmenopausal women.
A recent cross-sectional study involving 340 African Americans with type 2 diabetes (http://mpkb.org/home/diseases/diabetes2) found that serum 25-hydroxyvitamin D levels were positively associated with increased calcified atherosclerotic plaque in the aorta and carotid arteries.19 (http://mpkb.org/home/pathogenesis/vitamind#fn__19)
Depression and seasonal affective disorder
Main article: Sunshine or light exposure as a therapy (http://mpkb.org/home/othertreatments/sunshine)
According to the Marshall Pathogenesis, light-related changes in mood can be attributed to fluctuations in 1,25-dihydroxyvitamin D (1,25-D). Such reactions exist in people who suffer from “seasonal affective disorder (http://mpkb.org/home/othertreatments/sunshine)” as well as those who are addicted to or dependent upon tanning.
Contrary to popular belief, epidemiological research points to an increase in suicide across countries during the beginning of the summer months when people tend to get more light exposure.
Light exposure does nothing to resolve underlying disease state and can actually delay progress for Marshall Protocol (http://mpkb.org/home/mp) (MP) patients. Certainly prolonged light exposure has been shown to increase skin melanoma – the World Health Organization now categorizes tanning beds under the highest cancer risk category.20 (http://mpkb.org/home/pathogenesis/vitamind#fn__20)
MP patients who have completed the treatment have been able to attest to the fact that sunshine is not necessary for good health or happiness.
Despite what some researchers have argued, latitude studies (http://mpkb.org/home/pathogenesis/vitamind/latitude) that try to tie ambient solar UV radiation to prevalence of disease have been inconclusive.
Pregnancy
Main article: Pregnancy and vitamin D (http://mpkb.org/home/pathogenesis/vitamind/pregnancy)
1,25-D rises by 40% in the early pregnant decidua, meaning that its ability to dysregulate the nuclear receptors and the antimicrobial peptides (AmPs) they express is particularly prevalent during the first trimesters of pregnancy. The subsequent decrease in immune function slows immunopathology, resulting in symptomatic relief. But when the surge in 1,25-D disappears after pregnancy, AmP expression and immunopathology increase once again, leading to exacerbation of disease symptoms. This may explain why some women with autoimmune disease experience periods of palliation during gestation only to become increasingly symptomatic after giving birth.
Problems with some vitamin D research
Insufficient followup of study subjects
Main article: Immunosuppression and insufficient followup in vitamin D studies (http://mpkb.org/home/pathogenesis/vitamind/longterm)
One of the abiding weaknesses of studies on the effects of vitamin D on health is that researchers simply do not follow subjects consuming the secosteroid for a sufficient period of time. Instead, they tend to track subjects over the course of weeks, months, or one or two years, during the period of time when study participants are usually feeling the palliative effects of the steroid. This practice is a mistake as it does not account for the long-term immunosuppressive effects of a steroid.
Failing to control for biases inherent to observational studies
Main and related articles: Bias in observational epidemiological studies (http://mpkb.org/home/pathogenesis/vitamind/observational_bias), Latitude studies (http://mpkb.org/home/pathogenesis/vitamind/latitude)
It is arguably impossible to sufficiently control for the socioeconomic factors, which drive a person to participate in a therapy or take a supplement. The case of hormone replacement therapy (HRT) is instructive. For decades, researchers thought that HRT prevented disease, but it was ultimately shown that it caused it.
Studies of vitamin D's efficacy are especially fraught with challenges. For one, the secosteroid is palliative and the negative side effects can only be seen after decades of use. Also, people who take vitamin D are demonstrably different than those who don't. They almost always have a higher socioeconomic status.
Not all studies on vitamin D's efficacy are observational, but those that are may warrant a special amount of skepticism.
Mistaking correlation for causation
Main article: Mistaking correlation for causation in vitamin D studies (http://mpkb.org/home/pathogenesis/vitamind/correlation)
Many vitamin D studies suffer from methodological errors including bias inherent to using self-selected subjects (http://mpkb.org/home/pathogenesis/vitamind/observational_bias) and insufficient followup (http://mpkb.org/home/pathogenesis/vitamind/longterm), but perhaps their most egregious liability comes in mistaking correlation for causation.
It's undisputed that a wide array of studies point to the fact that 25-hydroxyvitamin D (25-D) – typically referred to in the media as vitamin D – is low in people with numerous chronic inflammatory diseases. However, these studies fail to prove that low 25-D causes disease. Even so, some studies assume that doubling serum levels of 25-D would drastically reduce mortality.21 (http://mpkb.org/home/pathogenesis/vitamind#fn__21)
In fact, molecular science has revealed that the levels of the vitamin D metabolites through a series of intricate and carefully controlled feedback pathways (http://mpkb.org/home/pathogenesis/vitamind/mechanisms), mechanisms that belie the simplistic first-order mass-action model used to guide the short-sighted vitamin studies. Also, epidemiological evidence suggests that while 25-D is low in chronic disease, 1,25-D (1,25-dihydroxyvitamin D) tends to be very high, an observation which is at odds with the theory that vitamin D deficiency causes or exacerbates disease.
There have been lots of observational studied showing an association between various diseases and vitamin D deficiency, but there is not any evidence yet that that is a casual relationship… it may be that vitamin D deficiency is a marker of ill health.
Dr. Ruth McQuillan, University of Edinburgh (http://www.nutraingredients.com/Product-Categories/Vitamins-premixes/Scottish-islands-selected-for-new-vitamin-D-study)

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A classic mistake in correlation vs. causation. This vintage advertisement implies that children are skinny because they eat and drink sugar. In the current age of skyrocketing obesity rates, sugar probably gets more blame than it deserves, but no one would say that sugar protects against obesity.
Populations that avoid vitamin D remain healthy despite low levels of 25-D
According to Professor Roger Bouillon of the University of Leuven, “over one billion” people worldwide need to increase their vitamin D intake due to vitamin D “deficiency.”22 (http://mpkb.org/home/pathogenesis/vitamind#fn__22) One Saudi study concluded that (http://www.springerlink.com/content/ll79786758173j04/) 87.8% of healthy men were “deficient.”
Yet, observational studies show that populations which avoid vitamin D consumption have naturally low levels of 25-D and remain healthy with such levels.


healthy Chilean women – A study which tested the level of 25-D in 90 “healthy, ambulatory Chilean women” showed that 27% of the premenopausal and 60% of the postmenopausal women had 25-D levels under 20 ng/ml.23 (http://mpkb.org/home/pathogenesis/vitamind#fn__23)
healthy Saudi medical students – A 2012 study collected data from 95 male and 103 female students with an average age of 19.5 years old. In 100% of the students, the vitamin D level was considered low. The mean 25-D level was 26.83 nmol/L in males and 16.03 nmol/L in females.
healthy Bangladeshi women – A study on healthy Bangladeshi women found that approximately 80% of the women had a level of 25-D under 16 ng/ml.24 (http://mpkb.org/home/pathogenesis/vitamind#fn__24) A separate study of premenopausal Bangladeshi women came to a similar conclusion.25 (http://mpkb.org/home/pathogenesis/vitamind#fn__25)
healthy Chinese infants – In a 1992 study, healthy full-term infants from China had serum concentrations of 25-D ranging from an average of 5 ng/ml to 14 ng/ml.26 (http://mpkb.org/home/pathogenesis/vitamind#fn__26)
healthy Omani women – A 2011 study of 41 apparently healthy women (ages 18-45 years) working at the Royal Hospital, Muscat, Oman found that all study subjects had 25-D levels below 50 nmol/L.27 (http://mpkb.org/home/pathogenesis/vitamind#fn__27)
young healthy adults in western India – Among young healthy adults from the western part of India, the average serum level of 25-D indicated vitamin D “deficiency”: 17.4 ng/ml.28 (http://mpkb.org/home/pathogenesis/vitamind#fn__28)
healthy Saudi Arabians – Severe hypovitaminosis D is widespread and more common in non-diabetics than diabetics in Saudi adults.29 (http://mpkb.org/home/pathogenesis/vitamind#fn__29) Nevertheless, this 2010 study's authors conclude a bit bizarrely, “The study further underscores the need for vitamin D fortification of the Saudi diet, and the promotion of vitamin D supplementation in both groups.”
healthy lactating mothers – Even when lactating mothers take all but exceedingly high levels of vitamin D – 6,000 IU which is 15 times the United States' Recommended Daily Intake – the vitamin D content in breast milk remains very low.30 (http://mpkb.org/home/pathogenesis/vitamind#fn__30) This is confusing for advocates of vitamin D supplementation who would think that breastfeeding mothers would give their infant extra levels of vitamin D during formative stages of growth.

The Vitamin D Council, an organization that advocates vitamin D supplementation, states (http://www.vitamindcouncil.org/researchPregnancy.shtml):
One of the great mysteries in human biology is the fact that most human breast milk is deficient in vitamin D. How could Nature overlook such an important nutrient in the “perfect food”?
Vitamin D Council
One research team, studying patients with xeroderma pigmentosum, a genetic disorder in which patients are unable to repair damage caused by ultraviolet light, found that vitamin D levels are maintained even when patients practice at least six years of rigorous photoprotection and not supplementing with vitamin D. More importantly, the researchers also concluded that the clinical manifestations of vitamin D “deficiency” were absent.
The patients all wore protective clothing and sunscreens when outdoors. Estimated mean vitamin D intake was normal. The mean values of serum 25-OHD were low normal, but 1,25-(OH)2D, calcium, ionized calcium and parathyroid hormone levels were normal …. Despite rigorous sun protection normal vitamin D levels can be maintained in ambulatory patients with XP.
[I]Armando Sallitto et al.31 (http://mpkb.org/home/pathogenesis/vitamind#fn__31)
Ramifications of a simplistic understanding of vitamin D metabolism
Numerous studies have identified patient populations that are “deficient” in vitamin D. Patients suffering from obesity (http://mpkb.org/home/diseases/obesity), schizophrenia, fibromyalgia (http://mpkb.org/home/diseases/fibromyalgia), multiple sclerosis, autism, etc. all seem to be suffering from vitamin D deficiency. One could list hundreds of such studies (http://mpkb.org/home/pathogenesis/vitamind/low25d).
Although it is not unheard of, few seem to explore the possibility that a low 25-D is the result of disease. Perhaps it is because researchers conceptualize vitamin D as they might a resource which gets used up and needs to be replenished – not unlike gasoline when a car runs low. This metaphor is not at all apt, because vitamin D is regulated like the steroid it is.32 (http://mpkb.org/home/pathogenesis/vitamind#fn__32) 33 (http://mpkb.org/home/pathogenesis/vitamind#fn__33)
Large segments of the population are consuming vitamin D at historic levels. Like the first-line treatment for many autoimmune diagnoses, the corticosteroid (http://mpkb.org/home/othertreatments/corticosteroids) Prednisone, vitamin D temporarily reduces symptoms of disease, but long-term use dramatically increases the odds of disease relapse.34 (http://mpkb.org/home/pathogenesis/vitamind#fn__34)
In practice, widespread and systematic supplementation of vitamin D may serve to drive a kind of self-fulfilling prophesy. When whole populations are given large amounts of vitamin D, the only members of that population who remain “deficient” are those whose immune systems are fighting disease by actively downregulating 25-D. In other words, the more rigorously vitamin D is added to milk, juice, snack bars, and breakfast cereals, the less likely it is that someone has low levels of vitamin D but no chronic disease.
Supplemental vitamin D given to healthy people
According to the Marshall Pathogenesis, limited amounts of vitamin D may be helpful for a time to healthy people. Because the body is able to properly regulate the VDR, ingested vitamin D is rapidly converted into 1,25-D, which activates the VDR. This may explain the one (barely) significant finding from a 2011 Cochrane systematic review.35 (http://mpkb.org/home/pathogenesis/vitamind#fn__35) (Publication bias (http://mpkb.org/home/pathogenesis/vitamind/cancer#randomized_controlled_trials_of_vitamin_d_i ntake) may have also tilted the findings towards intervention.) However, this is certainly no basis for forced fortification.
Marshall Protocol and vitamin D
As opposed to certain treatments which employ sunshine or light therapy (http://mpkb.org/home/othertreatments/sunshine), patients on the Marshall Protocol (http://mpkb.org/home/mp) (MP) use the VDR agonist (http://mpkb.org/home/pathogenesis/vitamind/metabolism), olmesartan (http://mpkb.org/home/mp/olmesartan), and pulsed, low-dose antibiotics to gradually eliminate the Th1 pathogens. Patients on the treatment must refrain from supplementing with vitamin D or eating any foods that contain vitamin D. These measures allow 25-D levels to drop to a point where the VDR can most optimally activate the innate immune system.
Because the vitamin D metabolites are dysregulated in chronic disease, most patients on the MP also become sensitive to light. Although light sensitivity improves as the Th1 pathogens are killed, most patients must avoid bright sunlight and block bright light in the eyes with special sunglasses during the healing process. However, once the Th1 pathogens have been killed and the vitamin D metabolites have re-stabilized, patients are able to tolerate sunlight and bright lights once again.

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Related publications and presentations
• Paper - Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b

• Paper - Vitamin D discovery outpaces FDA decision making

• Paper - Vitamin D: the alternative hypothesis

• Presentation - Bacteria induced vitamin D receptor dysfunction in autoimmune disease: theoretical and practical implications for interpretation of serum vitamin D metabolite levels

• Presentation - VDR receptor competence induces recovery from chronic autoimmune disease

• Presentation - Vitamin D induced dysregulation of nuclear receptors may account for higher prevalence of some autoimmune diseases in women

• Presentation - Vitamin D metabolites as clinical markers in autoimmune and chronic illness

Read more
• Second-guessing the consensus on vitamin D – a critical analysis of research used to support increasing population-wide levels of vitamin D supplementation
• Skepticism Grows Regarding Widespread Vitamin D Supplementation
• Children born and living without sunlight – In 2012, it was learned that 27 children had been living underground as members of a Muslim sect. Many had lived there for their entire lives and had never seen daylight. The conditions of these children was pronounced as “satisfactory” by pediatricians.
• Vitamin D Intolerance – “I get sick as a dog.” Lyme and autoimmune patients commiserate with one another over feeling worse after taking vitamin D.
• The Truth About Vitamin D – plain language summary of the evidence for vitamin D, as of 2011
Keywords: Pathogenesis
References
1 Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln MR, Burrell A, Handunnetthi L, Handel AE, Disanto G, Orton SM, Watson CT, Morahan JM, Giovannoni G, Ponting CP, Ebers GC, Knight JC A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res. 2010;20:1352-60.
2 Arnson Y, Amital H, Shoenfeld Y Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum Dis. 2007;66:1137-42.
3 Jolliffe DA, Griffiths CJ, Martineau AR Vitamin D in the prevention of acute respiratory infection: systematic review of clinical studies. J Steroid Biochem Mol Biol. 2012;:.
4 Wejse C, Gomes VF, Rabna P, Gustafson P, Aaby P, Lisse IM, Andersen PL, Glerup H, Sodemann M Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2009;179:843-50.
5 Avenell A, Cook JA, Maclennan GS, Macpherson GC Vitamin D supplementation to prevent infections: a sub-study of a randomised placebo-controlled trial in older people (RECORD trial, ISRCTN 51647438). Age Ageing. 2007;36:574-7.
6 Lehouck A, Mathieu C, Carremans C, Baeke F, Verhaegen J, Van Eldere J, Decallonne B, Bouillon R, Decramer M, Janssens W High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med. 2012;156:105-14.
7 Murdoch DR, Slow S, Chambers ST, Jennings LC, Stewart AW, Priest PC, Florkowski CM, Livesey JH, Camargo CA, Scragg R Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. JAMA. 2012;308:1333-9.
8 Li-Ng M, Aloia JF, Pollack S, Cunha BA, Mikhail M, Yeh J, Berbari N A randomized controlled trial of vitamin D3 supplementation for the prevention of symptomatic upper respiratory tract infections. Epidemiol Infect. 2009;137:1396-404.
9 Proud D, Turner RB, Winther B, Wiehler S, Tiesman JP, Reichling TD, Juhlin KD, Fulmer AW, Ho BY, Walanski AA, Poore CL, Mizoguchi H, Jump L, Moore ML, Zukowski CK, Clymer JW Gene expression profiles during in vivo human rhinovirus infection: insights into the host response. Am J Respir Crit Care Med. 2008;178:962-8.
10 Kimball S, Vieth R, Dosch HM, Bar-Or A, Cheung R, Gagne D, O'Connor P, D'Souza C, Ursell M, Burton JM Cholecalciferol Plus Calcium Suppresses Abnormal PBMC Reactivity in Patients with Multiple Sclerosis. J Clin Endocrinol Metab. 2011;:.
11 Agborsangaya CB, Lehtinen T, Toriola AT, Pukkala E, Surcel HM, Tedeschi R, Lehtinen M Association between Epstein-Barr virus infection and risk for development of pregnancy-associated breast cancer: Joint effect with vitamin D? Eur J Cancer. 2010;:.
12 , 14 Sadeghi K, Wessner B, Laggner U, Ploder M, Tamandl D, Friedl J, Zügel U, Steinmeyer A, Pollak A, Roth E, Boltz-Nitulescu G, Spittler A Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol. 2006;36:361-70.
13 Do JE, Kwon SY, Park S, Lee ES Effects of vitamin D on expression of Toll-like receptors of monocytes from patients with Behcet's disease. Rheumatology (Oxford). 2008;47:840-8.
15 Dickie LJ, Church LD, Coulthard LR, Mathews RJ, Emery P, McDermott MF Vitamin D3 down-regulates intracellular Toll-like receptor 9 expression and Toll-like receptor 9-induced IL-6 production in human monocytes. Rheumatology (Oxford). 2010;49:1466-71.
16 Hopkins MH, Owen J, Ahearn TU, Fedirko V, Flanders WD, Jones DP, Bostick RM Effects of supplemental vitamin D and calcium on biomarkers of inflammation in colorectal adenoma patients: A randomized, controlled clinical trial. Cancer Prev Res (Phila). 2011;:.
17 Swales HH, Wang TJ Vitamin D and cardiovascular disease risk: emerging evidence. Curr Opin Cardiol. 2010;22:513-7.
18 Vitamin D May Not Have Cardioprotective Benefits
19 Freedman BI, Wagenknecht LE, Hairston KG, Bowden DW, Carr JJ, Hightower RC, Gordon EJ, Xu J, Langefeld CD, Divers J Vitamin d, adiposity, and calcified atherosclerotic plaque in african-americans. J Clin Endocrinol Metab. 2010;95:1076-83.
20 El Ghissassi F, Baan R, Straif K, Grosse Y, Secretan B, Bouvard V, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, Cogliano V A review of human carcinogens--part D: radiation. Lancet Oncol. 2009;10:751-2.
21 Grant WB An estimate of the global reduction in mortality rates through doubling vitamin D levels. Eur J Clin Nutr. 2011;65:1016-26.
22 Boullion, R. (2006 April 2). Vitamin D analogues: pharmacology and therapeutic uses. European Congress of Endocrinology, Glasgow.
23 González G, Alvarado JN, Rojas A, Navarrete C, Velásquez CG, Arteaga E High prevalence of vitamin D deficiency in Chilean healthy postmenopausal women with normal sun exposure: additional evidence for a worldwide concern. Menopause. 2007;14:455-61.
24 Islam MZ, Akhtaruzzaman M, Lamberg-Allardt C Hypovitaminosis D is common in both veiled and nonveiled Bangladeshi women. Asia Pac J Clin Nutr. 2006;15:81-7.
25 Islam MZ, Lamberg-Allardt C, Kärkkäinen M, Outila T, Salamatullah Q, Shamim AA Vitamin D deficiency: a concern in premenopausal Bangladeshi women of two socio-economic groups in rural and urban region. Eur J Clin Nutr. 2002;56:51-6.
26 Specker BL, Ho ML, Oestreich A, Yin TA, Shui QM, Chen XC, Tsang RC Prospective study of vitamin D supplementation and rickets in China. J Pediatr. 1992;120:733-9.
27 Al-Kindi MK Vitamin D Status in Healthy Omani Women of Childbearing Age: Study of female staff at the Royal Hospital, Muscat, Oman. Sultan Qaboos Univ Med J. 2011;11:56-61.
28 Shivane VK, Sarathi V, Bandgar T, Menon P, Shah NS High prevalence of hypovitaminosis D in young healthy adults from the western part of India. Postgrad Med J. 2011;:.
29 Al-Daghri NM, Al-Attas OS, Al-Okail MS, Alkharfy KM, Al-Yousef MA, Nadhrah HM, Sabico SB, Chrousos GP Severe hypovitaminosis D is widespread and more common in non-diabetics than diabetics in Saudi adults. Saudi Med J. 2010;31:775-80.
30 Wagner CL, Hulsey TC, Fanning D, Ebeling M, Hollis BW High-dose vitamin D3 supplementation in a cohort of breastfeeding mothers and their infants: a 6-month follow-up pilot study. Breastfeed Med. 2006;1:59-70.
31 Sollitto RB, Kraemer KH, DiGiovanna JJ Normal vitamin D levels can be maintained despite rigorous photoprotection: six years' experience with xeroderma pigmentosum. J Am Acad Dermatol. 1997;37:942-7.
32 Moan J, Lagunova Z, Lindberg FA, Porojnicu AC Seasonal variation of 1,25-dihydroxyvitamin D and its association with body mass index and age. J Steroid Biochem Mol Biol. 2009;113:217-21.
33 Schwartz JB Effects of vitamin D supplementation in atorvastatin-treated patients: a new drug interaction with an unexpected consequence. Clin Pharmacol Ther. 2009;85:198-203.
34 Gottlieb JE, Israel HL, Steiner RM, Triolo J, Patrick H Outcome in sarcoidosis. The relationship of relapse to corticosteroid therapy. Chest. 1997;111:623-31.
35 Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, Bjelakovic M, Gluud C Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2011;7:CD007470.
36 Goswami R, Gupta N, Goswami D, Marwaha RK, Tandon N, Kochupillai N Prevalence and significance of low 25-hydroxyvitamin D concentrations in healthy subjects in Delhi. Am J Clin Nutr. 2000;72:472-5.
37 Crew KD, Shane E, Cremers S, McMahon DJ, Irani D, Hershman DL High prevalence of vitamin D deficiency despite supplementation in premenopausal women with breast cancer undergoing adjuvant chemotherapy. J Clin Oncol. 2009;27:2151-6.
38 Wjst M Introduction of oral vitamin D supplementation and the rise of the allergy pandemic. Allergy Asthma Clin Immunol. 2009;5:8.

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Metabolism of vitamin D and the Vitamin D Receptor
A number of studies have suggested that patients with chronic inflammatory diseases are deficient in 25-hydroxyvitamin-D (http://mpkb.org/home/tests/25d) (25-D) and that consuming greater quantities of vitamin D, which elevates 25-D levels, alleviates symptoms of disease. Some years ago, molecular biology identified 25-D as a secosteroid. Secosteroids would typically be expected to depress inflammation (http://mpkb.org/home/pathogenesis/innate_immunity#inflammation), which is in line with the reports of symptomatic improvement. The simplistic first-order mass-action model used to guide the early vitamin studies has given way to a more complex description of action. When active, the Vitamin D nuclear receptor (http://mpkb.org/home/pathogenesis/innate_immunity#role_of_vitamin_d_receptor_in_inna te_immunity) (VDR) affects transcription of at least 913 genes and impacts processes ranging from calcium metabolism to expression of key antimicrobial peptides (http://mpkb.org/home/pathogenesis/innate_immunity#antimicrobial_peptides).
Located in the nucleus of a variety of cells including immune cells, the VDR is a control system of sorts. When exposed to infection and damage, especially that which is caused by pathogens, the body begins to convert the inactive form 25-D into the active form, 1,25-D (http://mpkb.org/home/tests/125d). As cellular concentrations of 1,25-D increase, 1,25-D activates the VDR, turning on any number of genes the receptor transcribes.
According to a 2010 analysis, the VDR significantly affects 229 human genes. Many of these genes have long been associated with autoimmune diseases (http://mpkb.org/home/alternate/autoimmunity) and cancers (http://mpkb.org/home/diseases/cancer) including, for example, the genes IRF8 (linked to multiple sclerosis (http://mpkb.org/)), and PTPN2 (connected to Crohn's disease (http://mpkb.org/home/diseases/ibd) and type I diabetes (http://mpkb.org/home/diseases/diabetes1)).1 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__1) The activation of certain genes also leads to the synthesis of antimicrobial peptides. The antimicrobial peptides are the body's “natural antibiotics” and have a potent anti-bacterial effect.
However, bacteria create ligands, which like 25-D, inactivate the VDR and, in turn, the innate immune response (http://mpkb.org/home/pathogenesis/innate_immunity). This allows the microbes to proliferate. In response, the body increases production of 1,25-D from 25-D, leading to one of the hallmarks of chronic inflammatory disease: a low 25-D and a high 1,25-D.
This pattern is a result of the disease process rather than a cause. For a variety of reasons, neither increased consumption of vitamin D nor the body's synthesis of additional 1,25-D is ultimately effective at combatting infection.
Vitamin D Receptor (VDR) controls innate immunity
Related article: Innate immune response and Th1 inflammation (http://mpkb.org/home/pathogenesis/innate_immunity)
The innate immune response (http://mpkb.org/home/pathogenesis/innate_immunity) is the body's first line of defense against and non-specific way for responding to bacterial pathogens.2 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__2) Located in the nucleus of a variety of cells, the Vitamin D nuclear receptor (http://mpkb.org/home/pathogenesis/innate_immunity#role_of_vitamin_d_receptor_in_inna te_immunity) (VDR) plays a crucial, often under-appreciated, role in the innate immune response.
When functioning properly, the VDR transcribes between hundreds3 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__3) and thousands of genes4 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__4) including those for the proteins known as the antimicrobial peptides (http://mpkb.org/home/pathogenesis/innate_immunity#antimicrobial_peptides). Antimicrobial peptides are “the body's natural antibiotics,” crucial for both prevention and clearance of infection.5 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__5) The VDR also expresses the TLR2 receptor, which is expressed on the surface of certain cells and recognizes foreign substances.
The body controls activity of the VDR through regulation of the vitamin D metabolites. 25-hydroxyvitamin D (25-D (http://mpkb.org/home/tests/25d)) antagonizes or inactivates the Receptor while 1,25-dihydroxyvitamin D (http://mpkb.org/home/tests/125d) (1,25-D) agonizes or activates the Receptor.
Another component of the innate immune response is the release of inflammatory cytokines (http://mpkb.org/home/pathogenesis/innate_immunity#inflammation). The result is what medicine calls inflammation, which generally leads to an increase in symptoms.
Before the Human Microbiome (http://mpkb.org/home/pathogenesis/microbiota) Project, scientists couldn't link bacteria to inflammatory diseases. But with the advent of DNA sequencing technology, scientists have detected many of the bacteria capable of generating an inflammatory response. All diseases of unknown etiology are inflammatory diseases.
Greater than 36 types of tissue have been identified as having a Vitamin D Receptor.6 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__6)
Regulating the VDR
file:///C:\DOCUME~1\RAFA~1\USTAWI~1\Temp\msohtmlclip1\01\c lip_image001.gif (http://mpkb.org/_detail/home/pathogenesis/vitamind/25dvs125d.gif?id=home%3Apathogenesis%3Avitamind%3A metabolism)
1,25-D is different than 25-D in that it possesses a single 1-alpha hydroxylation. It is this additional hydroxylation, which stabilizes helix 12 in the Vitamin D Receptor binding the promoter which allow activation of the VDR and leads to the transcription of thousands of genes.
A general appreciation for how 25-D and 1,25-D compete for nuclear receptors (http://mpkb.org/home/pathogenesis/innate_immunity#nuclear_receptors_and_ligands) gets to the heart of their opposing roles in the body. According to the Marshall Pathogenesis (http://mpkb.org/home/pathogenesis), the VDR is foremost a control system. Under most circumstances, the active form, 1,25-D, acts as the “on” switch and the inactive form, 25-D, is the “off” switch.7 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__7) 25-D is not completely inactive, but it does not and cannot activate the VDR. As Leow states in Respirology, “25-D levels are not associated with levels of cathelicidin or beta-defensin-2 [antimicrobial proteins transcribed by the VDR].”8 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__8)
Further underscoring this role for these two D metabolites is that 25-D and 1,25-D “happen” to share similar binding affinities for the VDR. According to molecular modeling by Trevor Marshall, PhD, 1,25-D has an affinity of 8.48 (as measured by nanomolar Kd) and 25-D has an affinity of 8.36.9 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__9) It would seem that activation of the Vitamin D nuclear receptor is achieved by a delicate balance between the concentrations of a number of endogenous hormones. Indeed, at the risk of overgeneralization, the body increases and decreases the production of 1,25-D to control the innate immune response.
As mentioned before, exposure to injury and infection enhances production of 1,25-D, which in turn leads to the creation of antimicrobial peptides and activation of TLR2.
However, certain feedback mechanisms are also in place, which allow the body to limit the production of 1,25-D to just that amount needed for proper transcriptional activation of the VDR.


When the VDR is activated, it transcribes the gene for the enzyme CYP24A1 (http://mpkb.org/home/pathogenesis/vitamind/mechanisms), which increases conversion of 1,25-D into inactive metabolites.
An activated VDR also controls 1,25-D concentration by limiting transcription of the gene CYP27B1, which converts 25-D into 1,25-D.10 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__10)

Bacteria and the VDR
The Antimicrobial Peptide Database (http://aps.unmc.edu/AP/main.php) lists hundreds of antimicrobial peptides known to kill or inhibit the reproduction of bacteria,11 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__11) 793 AmPs found in animals as of January 5, 2009. The sheer diversity of these proteins coupled with the fact that they have been conserved over millenia suggests that enough pathogenic bacteria exist in sufficient quantities to warrant the evolution of these defense mechanisms. It would seem that is in the strong interest of the human body to destroy or disrupt these bacteria.
Pathogenic bacteria are likewise driven by evolutionary impetus: it's in their interest to disrupt the proteins, which interfere with their growth. In what way or ways could bacteria interrupt production of the AmPs?
According to one researcher, it is nearly impossible for bacteria to develop resistance to the AmPs:
Acquisition of resistance by a sensitive microbial strain against antimicrobial peptides is surprisingly improbable.
Michael Zasloff 12 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__12)
However, what if it were possible to disrupt the expression of the Vitamin D Receptor by secreting ligands, which bind to and inactivate the receptor? Such bacteria would have an undeniable reproductive advantage.
Think about this for a minute – if you were a persistent pathogen, wouldn’t it seem a good idea to disable your host’s ability to produce antimicrobial peptides? And if you discovered

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that disabling just one receptor, the VDR, would get rid of both cathelicidin and defB2, wouldn’t you try to evolve a mechanism for doing that?
Trevor Marshall, PhD
Bacteria disable the VDR


Capnine is a protein created by bacteria, a protein which may bind to and antagonize (inactivate) the VDR. The secretion of capnine and substances like it fulfills an important evolutionary need for bacteria: to disrupt the innate immune response.
In the arms race of host–microbe co-evolution, successful microbial pathogens have evolved ingenious ways to evade host immune responses.13
Studies have indicated that the dysregulation of VDR may lead to exaggerated inflammatory responses, raising the possibility that defects in Vitamin D and VDR signaling transduction may be linked to bacterial infection and chronic inflammation. Further characterization of Vitamin D/VDR will help elucidate the pathogenesis of various human diseases and in the design of new approaches for prevention and treatment.
Jun Sun 14
Since the VDR is at the heart of the innate immune system, bacteria can survive by discovering how to disable it through a variety of different actions. Actions accumulate and are more powerful than individual actions.
In keeping with evolutionary theory, a growing number of substances and species have been shown to downregulate the activity of the VDR:
• Borrelia burgdorferi – Live Borrelia burgdorferi reduced VDR expression in monocytes (phagocytes) by 50 times, and lysates (“dead” Borrelia) reduced it by 8 times15
• Mycobacterium tuberculosis – shown to downregulate the VDR 3.3-fold 16 which makes sense given that an active VDR helps phagocytes to suppress the intracellular growth of M. tuberculosis 17 18
• Mycobacterium leprase – produces microRNA-21 to target multiple genes associated with the VDR19
• “Gliding” biofilm bacteria have been shown to create Capnine – Capnine is a 2-amino-3-hydroxy-15-methylhexadecane-1-sulfonic acid, and is created by the genera Cytophaga, Capnocytophaga, Sporocytophaga, and Flexibacter.20 21 The secretion of capnine meets an important evolutionary need for bacteria. Capnine possesses a high affinity for the VDR as evidenced by the fact that molecular modeling shows that its stable in the ligand binding pocket. Molecular modeling further shows that when capnine is docked in the VDR, it inactivates the receptor.
• Chlamydia trachomatis – shown to downregulate the VDR in unpublished work
The following substances reduce the number of VDR, without which immune function is limited:
• Caspase-3 – A protein which cleaves (breaks apart) the VDR structure and thus limits the ability of VDR to perform gene transcription.22 The caspases are upregulated by Shigella infection,23 which implies that the VDR may have a faster cycle time in disease than in health.
According to the Marshall Pathogenesis, pathogens' production of ligands, which bind to and antagonize (inactivate) the Vitamin D Receptor, is one of the fundamental processes by which chronic inflammatory disease occurs. The consumption of other immunosuppressive substances also has an effect.

Studies have shown that at least several pathogens downregulate VDR expression.
One promising area for future research is to fully characterize the breadth and diversity of proteins created by bacteria in infected cells.
Murine models of VDR offer some confirmation
One can see the effects of a dysfunctional VDR in knockout mice, mice genetically engineered to be born without the receptor. These mice demonstrate what it is like to have a VDR completely blocked by bacterial ligands.
Mice without a VDR have been shown in separate studies to be born with alopecia, an inflammatory condition in which organisms have no hair24 and age prematurely.25 Scientists have also found that Salmonella is much more virulent and aggressive in mice in which the vitamin D receptor had been turned off.26 These mice showed higher levels of activity of inflammatory molecules, and they lost weight more quickly and were much more likely to die in response to infection.
Further validating the Marshall Pathogenesis model is this: other research in VDR knockout mice has shown a marked increase, by a factor of ten, in serum 1,25-D and a clear reduction - to almost undetectable levels - in serum 25-D. Such levels persisted at seven weeks until the mice eventually died.27
Mechanisms by which bacteria affect levels of 25-D and 1,25-D
Main article: Mechanisms by which bacteria affect levels of 25-D and 1,25-D
A chronic pathogenic microbiota affects the levels of the D metabolites observed in chronic diseases in several ways. When the immune system is challenged by pathogens, the body activates CYP27B1, causing more 25-D to be converted to 1,25-D, which, of course, increases activity of the VDR.
However, just because the concentration of 1,25-D reaches high levels - sometimes extremely high values - does not mean that the hormone is successful in binding and activating all of the body's Vitamin D Receptors (VDR). In fact, a 1,25-D that is elevated for an extended period of time suggests that the activity of the VDR is at least partially blocked.
When bacterial ligands block the VDR, the Receptor is prevented from transcribing CYP24A1, a well-studied enzyme which breaks down excess 1,25-D.
A full understanding of all these mechanisms supports the conclusion that elevated 1,25-D and depressed 25-D are a result rather than a cause of the inflammatory disease process.
Viruses and fungi also affect the VDR
• Epstein-Barr virus (EBV) – shown to downregulate expression of the VDR (and by the VDR) by a factor of about five, inducing “eventual immortalization”28 A 2011 paper further showed that a EBV not only down-regulates expression of the VDR protein itself, but also acts to block transcription by the VDR.29
• HIV – binds to the VDR30 and inhibits conversion of 25-D into 1,25-D31 (see below)
• Aspergillus fumigatus – In cystic fibrosis patients, the fungus A. fumigatus has been shown to secrete gliotoxin, a toxin which dose-dependently downregulates VDR mRNA and protein levels. This directly results in decreased levels of the AmP LL-37, thereby “providing an opportunistic environment for both bacterial and fungal colonization.”32 33

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Cytomegalovirus – Cytomegalovirus affects hundreds of genes including downregulating the VDR 2.2 fold.34 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__34)
Hepatitis C virus – Gal-Tanamy et al. showed that HCV infections interfere with the VDR by inhibiting the creation of CYP24A1, the enzyme responsible for breaking down excess 1,25-D.35 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__35)

Evidence for high 1,25-D in patients with chronic disease
Under most normal conditions, serum levels of 1,25-dihydroxyvitamin D are constant throughout the year (no variability due to sun exposure), but there is no such tight biochemical regulation in at least some chronic inflammatory diseases such as obesity (http://mpkb.org/home/diseases/obesity).36 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__36)
At the site of infection
It is sometimes thought that the liver and kidney are the only sites for conversion of 25-D into 1,25-D, but there is evidence that this process happens outside those organs – not coincidentally, at the very sites where patients report symptoms of chronic disease. High levels of 1,25-D and the enzyme which leads to the production of 1,25-D, 1 α-hydroxylase, have been found at various locations where the human body needs a strong host defense.37 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__37)


skin cells of sarcoidosis (http://mpkb.org/home/diseases/sarcoidosis) patients – Sarcoidosis patients have a variety of skin symptoms including bumps, ulcers, or discolored skin. Zehnder et al found increased expression of the enzyme 1 α-hydroxylase – the enzyme which converts 25-D into 1,25-D – in the skin cells of sarcoidosis patients.38 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__38) They write:

In particular, the expression of 1α-OHase [1 α-hydroxylase] by activated macrophages and epidermal keratinocytes [skin cells] suggests a role for 1,25(OH)2D3 [1,25-D] as an immunomodulatory and/or antiproliferative hormone.


synovial fluid surrounding the joints of patients with rheumatoid arthritis (http://mpkb.org/home/diseases/rheumatoid_arthritis) – Mawer et al found that 1,25-D levels were particulary elevated in the synovial fluid surrounding the joints of patients with rheumatoid arthritis (RA).39 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__39) In this study, median serum levels of 1,25-D at baseline was not elevated in the RA patients — only 24 pg/ml. Thus, the extrarenal synthesis of 1,25-D was not obvious from the routine blood test for 1,25-D. There is no reason to think that the metabolism of other diseases is any different.
immune cells including macrophages – Research has also shown that 1,25-D is synthesized in cells of the immune system, including the T cells and antigen-presenting cells40 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__40) as well as the macrophages.41 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__41) 42 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__42) The fact that the immune cells are a site for 1,25-D synthesis is notable, because it is these cell types, especially macrophages, which are often infected by the Th1 pathogens (http://mpkb.org/home/pathogenesis/microbiota).

There is strong evidence that the extrarenal enzyme located in macrophages plays a major role in certain granulomatous conditions (e.g., sarcoidosis), causing uncontrolled elevations of blood 1,25-(OH)2D3 levels….
Glenville et al.43 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__43)


respiratory epithelial cells – The primary lung epithelial cells, which play an important role in the defense against airborne pathogens, have been shown to express high baseline levels of activating 1 α-hydroxylase and low levels of inactivating 24-hydroxylase. This activity leads to increased expression of genes by the Vitamin D Receptor.44 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__44)

These disease site-specific peaks in 1,25-D somewhat undercuts the validity of the 1,25-D serum blood test as the gold standard for measuring the presence of chronic disease. There is currently no clinically available whole body test for elevated 1,25-D. For this reason, the ultimate measure of diseases treatable by the Marshall Protocol (http://mpkb.org/home/mp) is the therapeutic probe (http://mpkb.org/home/starting/therapeutic_probe).
file:///C:\DOCUME~1\RAFA~1\USTAWI~1\Temp\msohtmlclip1\01\c lip_image001.gif (http://mpkb.org/_detail/home/pathogenesis/vitamind/blaney125vs25.gif?id=home%3Apathogenesis%3Avitamin d%3Ametabolism)
A cohort of 100 patients was shown to have significantly (p<0.0001) higher serum levels of 1,25-D compared to the standard range. This data was described in Dr. Greg's Blaney's 2008 presentation (http://mpkb.org/home/publications/blaney_congress_on_autoimmunity_2008) at the International Congress on Autoimmunity in Portugal
In the blood serum
As 1,25-D increases, it sometimes leaks into the bloodstream where it can be detected by measures of the metabolite in blood serum, but certainly not always.
A number of studies have demonstrated that the level of the hormone 1,25-D rises in patients with certain chronic diseases.


autoimmune disease – Greg Blaney MD, a physician who practices in Vancouver, British Columbia (a setting with relatively infrequent sunlight), found that of a group of 100 patients with a variety of chronic inflammatory diseases, 85 had elevated measures of 1,25-D, which was defined as greater than or equal to 110 pmol/L.45 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__45)
Crohn's disease – One study found that in a cohort of 88 Crohn's disease patients, 35 patients or 40% had elevated levels of 1,25-D, which the authors defined as above 60 pg/mL.46 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__46)
obesity – Moan et al. showed that, in contrast to healthy people, patients with a high body mass index (BMI) had a significant seasonal variation in, not only 25(OH) vitamin D, but also of 1,25-D.47 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__47)
sarcoidosis – Kavathia et al found that in patients with sarcoidosis, those with high serum levels of 1,25-D have more pronounced chronic treatment needs.48 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__48)
asthma (http://mpkb.org/home/diseases/asthma) – Liu et al. showed that levels of vitamin D metabolites, particularly 1,25-D, were low within the airways and increased after allergen challenge. The increases correlated with the magnitude of inflammation and increases in cathelicidin.49 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__49)

Bell listed the following diseases and conditions, which manifest with high levels of 1,25-D: tuberculosis, AIDS with Pneumocystis carinii pneumonia, AIDS with cytomegalovirus infection, disseminated candidiasis, leprosy, rheumatoid arthritis, silicone-induced granulomas, Wegerner’s granulomatosis, Hodgkin’s disease, lymphoma, histocytic lymphoma, T-cell leukemia, plasma cell granuloma, leiomyoblastoma, seminoma, and subcutaneous fat necrosis.50 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__50)
Effect of high 1,25-D on nuclear receptors
In our study, the response to 1,25(OH)2D3 appears to be biphasic with a stimulatory effect at lower concentrations, and becoming inhibitory or ineffective at the higher levels.
Saveria Aquila et al.51 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__51)
At normal levels, the active vitamin D metabolite, 1,25-D, serves an important role in host defense,52 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__52) but high levels of the hormone are immunosuppressive53 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__53) – if for no other reason than the fact that it is calcitriol (1,25-D) and its analogues are used widely to treat autoimmune disease. One of the mechanisms by which 1,25-D may be immunosuppressive (and contribute to symptoms of disease) is by interacting with the body's other nuclear receptors. Selvaraj et al. have suggested that the high levels of 1,25-D seen in patients with pulmonary tuberculosis “might lead to downregulation of VDR expression” and that “decreased VDR levels could result in defective VDR signaling.”54 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__54) More recently, Johan Lundqvist's 2011 study showed that, consistent with the 2009 study by Proal et al. that “1α,25-dihydroxyvitamin D3 exerts tissue-specific effects on estrogen and androgen production and metabolism.”55 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__55)
Molecular modeling data show that at high levels, 1,25-D not only binds the VDR but also has a strong affinity for other key receptors that control the body's major hormonal systems including those that regulate the body's sex, thyroid, and adrenal hormones. As 1,25-D rises, it pushes out the molecules that are meant to control these receptors. Compromising these receptors can disrupt the body's ability to regulate temperature, libido, and any number of other functions.[table of affinities needed] Indeed, in the human brain, the VDR tends to be most common in the hypothalamus, which is responsible for these functions.56 (http://mpkb.org/home/pathogenesis/vitamind/metabolism#fn__56)
Molecular research also shows that, like the VDR, several of these nuclear receptors (including the alpha/beta thyroid receptors, glucocorticoid receptor, and androgen receptor) also express many families of antimicrobial peptides. A recent analysis of AmP expression by Brahmachary showed that the glucocorticoid receptor, the androgen receptor, and the Vitamin

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D Receptor, seem to be in control of 20, 17 and 16 families respectively, out of 22 analyzed.57 This means that when elevated 1,25-D displaces their endogenous ligands, the body's overall AmP expression is thwarted to an even greater degree. This further impairs the innate immune system's ability to combat chronic pathogens.
Case in point: thyroid receptor
Related article: Presentation - Vitamin D induced dysregulation of nuclear receptors may account for higher prevalence of some autoimmune diseases in women
1,25-D has a very high affinity for the alpha thyroid nuclear receptor (ThRa) having a Kd value of 8.41. Normally levels of the endogenous ligand for ThRa known as T3 (which has a Kd 7.20 for ThRa) keep 1,25-D out of the binding pocket, but as 1,25-D rises due to VDR dysregulation it starts to proportionately displace T3 and block transcription by ThRa. The same thing should happen with thyroid beta – 1,25-D has a Kd of 8.44 for that receptor.
When 1,25-D displaces T3, the genes with ThRa promoters are no longer transcribed, resulting in the phenomenon known as thyroid hormone resistance. Since related nuclear receptors work as a group, when transcription by ThRa is dysregulated, system wide gene transcription is also affected.
Case in point: androgen receptor
1,25-D has a kD of 8.05 for the androgen receptor, and a Kd of 8.12 for the glucocorticoid receptor. Elevated 1,25-D can displace cortisol and testosterone from their target receptors as well, leading to an array of other hormonal imbalances.
Effect of high 1,25-D on TACO
A primary action of 1,25-D is that a high level in susceptible individuals (e.g. during pregnancy and sun holidays) causes the cellular membrane protein TACO to allow tiny bacteria to freely enter and exit the immune cells, without causing the cells to die in the process.
Dr. Andy Wright has taken photos of [bacteria freely entering and exiting cells], and it obviously would allow the pathogen(s) to spread without restraint.
Trevor Marshall, PhD


If anything, patients with autoimmune disease are immunocompromised. A study of the prevalence of the key antimicrobial peptide showed that patients with sarcoidosis expressed it less than healthy subjects, and that sicker sarcoidosis patients expressed it least of all. Source: Kanchwala et al.
End-stage disease
As patients become sicker, their immune system becomes increasingly unable to mount a defense against infection. For example, Kanchwala et al. showed that patients with sarcoidosis expressed the antimicrobial peptide cathelicidin less than healthy subjects, and that sicker sarcoidosis patients expressed it least of all.58
One of the hallmarks of late-stage inflammatory diseases is a very low 1,25-D with HIV/AIDS being the most commonly cited example.
HIV/AIDS
Related article: HIV and AIDS
HIV is a viral infection, and AIDS is the syndrome, which results – according to the Marshall Pathogenesis – in a dysregulated vitamin D metabolism. As evidenced by the subset of people who survive for decades with HIV, the virus itself is not necessarily deadly. Instead, it is the co-infections which are the proximate cause of the disease. One can define the breadth of AIDS-related complications by the extent and number of co-infections such as pneumonia, herpes, Candida, etc.
Supporting this hypothesis, a number of terminal AIDS patients have neglible levels of 1,25-D. 18 of 29 patients in a study of AIDS patients had undetectable levels of the metabolite.59 The patients with depressed levels of 1,25-D were characterized by advanced clinical HIV infection, low CD4+ lymphocyte counts, and high serum levels of tumor TNF-alpha – all indication of more severe forms of the disease.
The exact mechanism by which 1,25-D is downregulated is not entirely known, but it is highly likely that it is caused by pathogens.
Haug et al theorized that TNF-alpha and possibly other cytokines – which pathogens are known to create60 – inhibit conversion of 25-D into 1,25-D in late-stage cases of HIV/AIDS.61
A second factor is that HIV disables D-Binding protein (DBP).62 63 DBP is the precursor for Macrophage Activating Factor (MAF) as it has a key role to play in attracting macrophages to sites of injury. 1,25-D is transported throughout the blood by DBP.
Cancer
Related article: Vitamin D and cancer
Higher levels of CYP24A1, the enzyme which breaks down excess 1,25-D, is associated with poorer survival in lung adenocarcinoma. In a 2011 study, CYP24A1 mRNA was elevated 8-50 fold in lung cancer (compared to normal non-cancerous lung) and significantly higher in less severe cancers.64
Lopes et al. showed that CYP24A1 expression was increased in metastatic breast cancer: 53.7% in invasive carcinomas compared to 19.0% of benign lesions.
From this study, we conclude that there is a deregulation of the Vitamin D signalling and metabolic pathways in breast cancer, favouring tumour progression. Thus, during mammary malignant transformation, tumour cells lose their ability to synthesize the active form of Vitamin D and respond to VDR-mediated Vitamin D effects, while increasing their ability to degrade this hormone.
N. Lopes,65

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Related publications and presentations




Paper - Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b (http://mpkb.org/home/publications/marshall_theoretical_2006)






Paper - Vitamin D discovery outpaces FDA decision making (http://mpkb.org/home/publications/marshall_bioessays_2008)






Paper - Vitamin D: the alternative hypothesis (http://mpkb.org/home/publications/albert_autoimmunity_reviews_2009)




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33 Coughlan C.A. et al. Downregulation Of The 1α, 25 Dihydroxyvitamin-D3 (Vitamin D3) Receptor By Aspergillus Fumigatus Secreted Gliotoxin In Cystic Fibrosis Am J Respir Crit Care Med 181;2010:A6184.
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[Gangsta Latino]

wyjdź na dwór jak będzie słoneczny dzień :P

[FIT-anula]

o w mordę jaki elaborat.

[fallenursus]

wyjdź na dwór jak będzie słoneczny dzień :P

Raczej nie :)

[Gangsta Latino]

wyszły jakieś nowe badania, które udowadniają, że dzięki promieniom słonecznym nie wytwarza się wit. D?

[fallenursus]

Skoro uważasz że wiecej jak połowa ludzibzyje w cieniu to moze te badania wyszły.

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jakas amerykanska fundacja zbadala ze u ludzi ktorzy maja choroby autoimunologiczne dieta bogata w kwasy nasycone tj ryby oleje tluszcze itp. podbija d 1,25 a ten skolei obniza wit D u ludzi z takimi horobami jak tarczyca, SM, AIDS, LYME disease, alzheimer, CFS, ALS, Fibromialgia, Schizofrenia, i inne występuje ten problem. Wtedy też słońce powoduje podbicie hormonu D. Ograniczają dietę słońce i biorą odpowiednie leki i to ma im pomagać.

[Gangsta Latino]

Nie rozumie o co Ci chodzi.
Napisałem tylko, że w uzupełnieniu wit. D pomagają promienie słoneczne, ale trzeba też pamiętać o dostarczaniu jej z jedzenia i/lub suplementów.
15-20 min na słońcu to tyle wit. D ile jest np. w ok. 100 gram żółtka, także nie jest to mała ilość.
Warto też kupić np. tran. Według mnie kupowanie samej wit. D w postaci supli to strata kasy.

[1577586]

chodzi ze ten artykół pisze o czymś innym że w pewnych przypadkach u ludzi z autoagresją zależność jest odwrotna.

[Gangsta Latino]

Autoagresja... warto to wkleić na forum emo. U nas chyba wielu takich nie ma

[fallenursus]

Nie zauważyłeś ze juznid dawna niechxeminsie oswiecsc ciemnigrodu? Zapyaj Julki jak unnuen z Wit d a przecież dietę ma bardzo dobra...

[Gangsta Latino]

Zacytuj to co napisałem w 21 poście w tym temacie i wskaż błędy.

[fallenursus]

Dwa.
Połowa forum narzeka na choroby przeziębienia i inne bzdety. Większość supli co dupki kupują ujemnie wpływa na system immunologiczny. Ciężkie treningi cardio i inne bzdety również.
Dla mnie to ty możesz nawet spać pod UV a poziom będziesz miał za mały. Oh no wait, but you dont Even lift...
:p
Ale tak na serio to jeszcze nikt kogo nie wysłałem na badania Wit d miał ja w normie. Jest to taki diabeł ze jesli jej za dużo mogą być nie przyjemne skutki uboczne a jeśli za mało to też nie zafajnie. Dawki dobierane są mniej więcej indywidualnie i jest to jedna z najtańszych witamin które można a nawet trzeba brać cały czas w dzisiejszych czasach.

[USgorn]

Z jedzenia to sie gowno tej witaminy dostarczy %-)
glownie z slonca tyle ze wiekszosc rokj tego slonca malo a i w tych czasach wiekszosc czasu ludzie w budynkach spedzaja

[1577586]

Autoagresja... warto to wkleić na forum emo. U nas chyba wielu takich nie ma

sa chorzy na tarczycę, z rakiem prostaty a poza tym ta przypadłość w ten sam sposób wpływa na obniżenie hormonów jak przy hipogonadyźmie.

[Gangsta Latino]

Ja zbytnio nie patrzę na innych, bo system immunologiczny to baaaaardzo złożona rzecz.
Ja od 2 lat chory byłem (chory czyli że przez kilka dni musiałem odpuścić treningi, brak apetytu itd.) 1 raz, a zbytnio nie przejmuję się wit. D. Chociaż od jakiś może hmm... 5 miesięcy znów biorę tran, żeby on sam uzupełniał mi 200% dziennej dawki. Do tego z diety jak sobie liczyłem też jakieś pół roku temu, mam ponad 100% (czasami mam pewnie ponad 300). Do tego jak jest lato dochodzą promienie więc mam ok. 400-600% bez żadnego kombinowania.

Ale nie napisałeś mi sedna sprawy. Co jest najlepszym wyjściem w zwiększeniu (dostarczeniu) wit. D według Ciebie?

[1577586]

napisze co w arcie ano ze dieta ktora obnizy wegle proste, tluszcze nasycone i nienasycone spowoduje ze hormon ktory ja obniza nie bedzie tego robil i poziom bedzie dobry, u chorych brak slonca tez obnizy hormon i wita pojdzie w gore. ale u zdrowych zaleznosci sa inne. wiec slonce jak najbardziej ok najlepiej natrzec sie ropa w upal wtedy fajnie łapie:)

[fallenursus]

Kapsy Wit d3. Zacząłem udezeniowo 5k dziennie po dwuch TyG zszedlem na 2-3 i tak ciagne. Nie brałem dwa TyG bo zapominalem kupić i czułem różnice w samopoczuciu a nawet się przeziembilem na kilka dni.

[1577586]

w tym arcie pisze ze badania pokazaly ze przyjmowanie wit d nie wskazuje na korzysci z tego i ze wazna jest dieta.

[1577586]

Patients on the treatment must refrain from supplementing with vitamin D or eating any foods that contain vitamin D. Rigorous photoprotection and not supplementing with vitamin D. More importantly, the researchers also concluded that the clinical manifestations of vitamin D “deficiency” were absent. Nie mogę dosłownie teraz znależć wzmianki o tym ale już to kiedyś przeczytałem żeby nie brać z zewnącz wit. d bo to nie daje efektów.

[fallenursus]

http://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

[1577586]

Oni podają sprzeczne stanowisko mają swoją kadrę wybitnych profesorów z całego świata i twierdzą że pierwotne założenia o tym by zwiękrzać D 1,25 OH są złe i tylko początkowo dają korzyści dla pacjentów lecz na dłuższą metę chorzy stają się bardziej schorowani układ kostny ich się degeneruje.

[Gangsta Latino]

no i znowu wychodzi na moje.
Jedni piszą, że trzeba przyjmować w postaci supli, inni że z jedzenia inni, że trzeba się opalać ;] . Dlatego, i się powtarzam, obecnie dużo wiadomo, a tak naprawdę gówno nadal wiadomo.