The MP treatment plan was originally designed to treat an inflammatory condition known as sarcoidosis. The treatment consists of using the drug Benicar, combined with the avoidance of all sources of vitamin D, and eventually adding various antibiotics, especially minocycline. After being used by sarcoidosis patients for some years, it was then theorized and claimed that the treatment could treat other inflammatory conditions. Eventually it was also claimed that it could treat fibromyalgia and CFS, conditions which are not recognized by the medical literature as being inflammatory in nature.
Sarcoidosis is an inflammatory disease, which is characterized by the presence of granulomas. Granulomas often occur as an immune response to certain types of infections and foreign bodies. However, no specific cause for sarcoidosis has yet been found. Many suspect an infectious cause, and studies are ongoing to find the infection. Others believe that while an infection may trigger the disease, that genetic and immune factors can significantly affect the course of the disease. Several articles state that over 50% of sarcoidosis patients eventually undergo remission without any treatment. The other patients develop a chronic form, which requires treatment to resolve. Steroids (glucocorticoids) that suppress the immune system are the main drugs that are used to treat sarcoidosis. Other immune suppressant drugs and antibiotics are also being used. However, many cases are hard to treat, and symptoms can last for years. Given the scarcity of traditional treatment options, it’s not surprising that someone has found an alternative way to treat it.
One of the main beliefs of the
MP is that an infection is the cause of all the conditions that the MP claims
it can treat, and that an excess of vitamin D prevents the body from properly
fighting the infection. Originally it
was believed that an excess of the active form of vitamin D, 1,25(OH)2D, was the problem.
However, the medical literature only mentions a few specific diseases
where this production contributes noticeable amounts of 1,25(OH)2D
to the circulating levels. Sarcoidosis is one of those diseases.
In conditions such as sarcoidosis, activation of immune cells, i.e. macrophages
and T cells, results in the production of 1,25(OH)2D.
The MP claimed that this was also occurring in unrelated conditions, such as
CFS, fibromyalgia, and chronic Lyme.
However, many people with those other conditions were not found to have
elevated 1,25(OH)2D.
This was eventually explained by the belief that the inactive form of
vitamin D, 25(OH)D, is capable of reducing
inflammation and blocking the production of 1,25(OH)2D. The MP claims that if people lower their
25(OH)D levels, by avoiding vitamin D intake, that this would result in
elevated levels of 1,25(OH)2D, and this would prove that inflammatory, or
“TH1 production” of 1,25(OH)2D was occurring. Furthermore, the MP also believes that 25(OH)D actually blocks 1,25(OH)2D from attaching to the vitamin
D receptor, preventing 1,25(OH)2D from properly stimulating the immune
system. The MP claims that this blocking
prevents the body from fighting the infection.
Thus, they now believe that 25(OH)D is also
harmful, and they recommend avoiding vitamin D, in order to reduce 25(OH)D to
below normal levels.
Positive Results from the MP
Do Not Prove the MP’s Vitamin D Theories.
Does vitamin D really hinder these diseases? The medical literature does not support this claim, nor does it support the belief that 25(OH)D blocks the effects of 1,25(OH)2D. And in fact, the avoidance of vitamin D in the MP treatment, has never been properly studied, to see what, if anything, it contributes to the effects of the treatment. The treatment was designed for sarcoidosis, and was then applied to other conditions, without testing to see whether avoidance of vitamin D is actually of any benefit for those other conditions. Perhaps, for those other conditions, only other aspects of the MP treatment are useful. For example, other treatments that simply use antibiotics, have been successful at treating inflammatory conditions. Indeed, there are even cases of sarcoidosis being successfully treated simply by antibiotics. Additionally, minocycline, which is the primary antibiotic use by the MP, may be especially potent in inhibiting granulomas.
And what about Benicar? Is Benicar helping sarcoidosis in the way that the protocol theorizes? ARBs such as Benicar have many useful effects on the body. Benicar not only has positive effects on the vascular system, but also has both anti-inflammatory and antioxidant effects. It may also be capable of increasing insulin sensitivity and affecting calcium metabolism. Studies about new effects of ARBs are constantly being published. Benicar could be helping sarcoidosis in one way, while helping other conditions in totally different ways. The MP claims that Benicar acts as a vitamin D agonist, but there is no lab study that supports this claim. Additionally, Benicar has not been studied at the high doses used by the MP, for the conditions that the MP treats. The more complete blocking of angiotensin II receptors at such high doses, may have even more positive effects than presently known. And it might be, that Benicar’s many positive effects, may be capable of offsetting the negative effects that occur from the vitamin D deficiency that results from being on the MP. Thus, there is no clear evidence that a reduction of vitamin D has any significant positive effects in the MP. Both Benicar and antibiotics are known to have many positive effects, for many different conditions, while there is no proof in the medical literature that reducing 25(OH)D to below normal levels, has any positive effects.
And what about the negative reactions to the MP treatment, that the MP claims is the body’s response to the killing of the infectious bacteria by the treatment. Are these reactions actually that, or are they simply side effects from the treatment?
The MP has yet to conduct any lab tests to support their theories. They have run computer simulations to support their beliefs about interactions of vitamin D metabolites, Benicar, and other substances, with the vitamin D receptor (VDR), but there is no guarantee that such simulations can accurately predict what actually happens in the body. For example, the author of the MP predicted that some of the statin drugs could interact with VDRs. But actual lab tests showed no such interaction. Indeed, the idea that such drugs have vitamin D type properties, was originally proposed by a non-MP researcher, and he has written that the MP author “is perhaps over-optimistic in suggesting that modern molecular biology can give precise answers to questions about actions of drugs because knowledge is inevitably incomplete.”
Since learning about the MP, I have tried to read as many medical studies as I could, that discuss sarcoidosis, ARBs, and vitamin D, and have learned many facts that I’ve not seen discussed elsewhere. Therefore, I’m presenting that information here, for anyone who is interested in the MP.
The intent of this web page is not to dissuade people from using the MP treatment. Instead, the intent is to question the validity of the theories connected with the treatment. These theories are often presented as being facts on MP web pages. Perhaps this is due to cognitive dissonance. Whatever the reason, many people who read those web pages end up believing that these theories are facts, when they are not. I have therefore decided to write this web page, in order to separate fact from theory, and to also point out when the MP theories are not supported by known facts. Given that the MP itself has changed some of its own views, such as recognizing that not everyone needs to avoid sunlight, we believe that it’s reasonable to question some of the other beliefs also.
The MP believes that excess 1,25(OH)2D production is occurring in many diseases, but the
MP defines the upper
limit for normal 1,25(OH)2D to be 45 pg/ml, while lab tests and studies define
it to be 60-65 pg/ml.
The MP believes that vitamin D metabolites play a role in sarcoidosis and many other diseases.
Vitamin D is a substance which the skin creates due to sunshine exposure. It is also found in supplements and certain foods. Vitamin D can either be stored in the body, or metabolized by the liver into 25(OH)D, which then circulates in the bloodstream and tissues. Only later is it then converted to the metabolite 1,25(OH)2D, which is the form that has hormonal active properties.
1,25(OH)2D
both stimulates and inhibits the immune system. 1,25(OH)2D
enhances the activity of immature immune cells (cell-lines, bone marrow cells),
while it inhibits the activity of more mature cells (peripheral blood monocytes
and peritoneal macrophages).
Some researchers believe that this dual effect allows 1,25(OH)2D
to stimulate the immune system, while providing a mechanism for preventing
overstimulation.
One of the ways that this comes into play, is when immune cells produce 1,25(OH)2D themselves. For example, when macrophage
immune cells are activated by the TH1 (inflammatory) cytokine IFN-gamma, they
are able to produce 1,25(OH)2D. This type of
production is far different from the more common renal production of 1,25(OH)2D, which is controlled by the presence of
calcium. Renal 1,25(OH)2D production controls
calcium levels in the body. Thus, if you
increase calcium intake, it will decrease the need for 1,25(OH)2D,
and renal 1,25(OH)2D production will be reduced.
However, TH1 production of 1,25(OH)2D does not respond
to calcium. And in certain conditions,
where excess inflammation occurs, excessive amounts of 1,25(OH)2D
can be generated, which is then reflected by increasing serum levels. However, this requires immune cells to be
activated, and this has not been shown to be occurring in conditions such as
CFS and fibromyalgia. Furthermore, IFN-gamma
is a necessary requirement for unregulated immune 1,25(OH)2D
production to occur. IFN-gamma is
increased in inflammatory conditions such as sarcoidosis, which helps to
explain the excess 1,25(OH)2D that occurs in those
conditions. However, IFN-gamma is not
increased in CFS and fibromyalgia. In
fact, in
CFS, IFN-gamma may actually be decreased.
Thus, there is a lack of evidence that 1,25(OH)2D
TH1 production occurs in those other conditions.
The MP believes that an excess of 1,25(OH)2D impairs the immune system in sarcoidosis, preventing it from properly fighting pathogens called Cell Wall Deficient bacteria, or CWD. (Note: CWD are not mycoplasmas.) Some researchers have theorized that CWDs play a role in a number of diseases. For example, lab studies have shown the possibility that CWD may alter the way the immune system responds to an infection, However, there still is much controversy regarding whether CWD have any significant effects in human disease, and studies have yet to confirm that CWDs play a role in sarcoidosis
In any event, if 1,25(OH)2D is somehow a factor in preventing a proper immune response against a pathogen, it would be important to know if significant TH1 1,25(OH)2D production was occurring. One way would be to simply test serum 1,25(OH)2D. The MP believes that if the serum level of 1,25(OH)2D is above 45 pg/ml, then it is abnormally high. They obtained this figure from the Merck manual. However, the Merck’s normal range of 1,25(OH)2D was defined decades ago, and is most likely based on older laboratory testing assays, which were known to have problems. The MP recommends using Quest laboratories to test 1,25(OH)2D levels. However, Quest themselves defines the normal range to be 15-60 for adults (27-71 for younger than 17 years). These values have been confirmed by studies. For example, in a study which showed that 1,25(OH)2D levels decrease with obesity, the average 1,25(OH)2D level for the study population was 108.2 pmol/L (41.6 pg/ml), with a standard deviation upper limit of 56.4 pg/ml.. However, for subjects with the lowest BMI (body mass index), the average 1,25(OH)2D was 45.8 pg/ml, with a standard deviation upper limit of 62.1 pg/ml. A previous similar study showed even higher levels, i.e. an average 1,25(OH)2D level of 44 pg/ml for obese subjects, versus 52 pg/ml for nonobese subjects The MP gives no clear reason why they believe that the upper limit should be according to Merck. Thus, many people are being told by the MP that they have elevated 1,25(OH)2D, when it might not necessarily be so.
Testing Methods used by the
MP for Dysregulated 1,25(OH)2D Production are flawed,
due to the fact that serum 1,25(OH)2D is affected by Calcium, Phosphate, PTH,
and other factors.
For many years, the MP also believed that excess production of 1,25(OH)2D could be proven by computing the ratio of serum 1,25(OH)2D to 25(OH)D. A high ratio was believed to indicate the presence of TH1 1,25(OH)2D production, and this meant that your condition could be treated by the MP. The MP now states that this test is often unreliable. Instead, they now use absolute levels of 1,25(OH)2D and 25(OH)D. But 1,25(OH)2D can be significantly influenced by many factors that have nothing to do with TH1 production of 1,25(OH)2D, so that neither the D-ratio nor the absolute test are reliable ways to prove TH1 production of 1,25(OH)2D. And it is because of the fact that 1,25(OH)2D levels can be influenced by many factors, that 25(OH)D is the main test used by the medical community to determine a vitamin D deficiency, and not 1,25(OH)2D.
The conversion rate of 25(OH)D to 1,25(OH)2D can vary due to a number of factors. For example, 1,25(OH)2D levels can vary significantly during the menstrual cycle. Also, a study has shown that women with PMS have high serum levels of 1,25(OH)2D, and low levels of 25(OH)D. This is partially due to a direct influence of estrogen on renal 1,25(OH)2D production. Estrogen supplementation has been shown to increase 1,25(OH)2D levels. Using the MP criteria, some of these women with PMS would be deemed by the MP to have TH1 1,25(OH)2D production, when they did not.
Although the D ratio test is used less, the MP web page still states that “a D-ratio that is higher then 2 is a sign of inflammation. A normal ratio in a healthy person is between 0.75 to 1.75.” However, in practice, normal people do have a ratio of 2 or higher. For example, a recent study on postmenopausal women aged 45-58, showed that the average ratio was 1.98. Additionally, this study compared women who had different forms of the vitamin D binding protein (DBP). DBP binds to vitamin D metabolites in the serum and tissues. Different genetic forms exist. The D ratio was found to be different for women who had different forms of the DBP. This is theorized to be due to the fact that the different forms have different metabolic rates. For women with one specific form, the D ratio was found to be an amazing 2.49. Thus, the D ratio test is flawed, yet it was used for many years to diagnose people with a TH1 condition. Therefore, it’s unknown how many people who have tried the MP during those years, really had a TH1 condition.
The most obvious flaw in measuring 1,25(OH)2D, is the fact that serum 1,25(OH)2D is significantly affected by dietary calcium. Taking more calcium, will decrease parathyroid (PTH) levels, which will then decrease 1,25(OH)2D levels. It is possible that some people on the MP who initially had high levels of 1,25(OH)2D, may simply have not been taking or absorbing enough calcium. And in fact, some people on the MP have eventually added calcium supplementation, which has then lowered both their PTH and 1,25(OH)2D levels. One wonders how many people who started the MP due to high 1,25(OH)2D levels, had high levels simply due to not taking enough calcium.
1,25(OH)2D production is also dependent on dietary phosphate Thus, in addition to calcium, phosphate also affects 1,25(OH)2D levels. Any changes in dietary phosphate, intestinal phosphate absorption, or renal phosphate reabsorption, can affect serum levels of 1,25(OH)2D. In fact, some people with CFS and fibromyalgia may actually have phosphate diabetes, a condition that depletes phosphate.
Another problem with the ratio test is the following requirement listed on an MP web page: “The D ratio is not a sufficient indicator of vitamin D dysregulation, especially when 25-D levels rise above 15 ng/ml.” The reason for this is the belief that 25(OH)D reduces inflammation and therefore blocks the TH1 production of 1,25(OH)2D. The problem with that statement, is that even in healthy people, at the levels of 25(OH)D that the MP recommends, a significant rise in PTH levels occurs, which results in increased levels of 1,25(OH)2D. Therefore, a high ratio of 1,25(OH)2D to 25(OH)D at those levels of 25(OH)D, can have nothing to do with increased inflammation, and thus cannot be used as an indicator of inflammation.
Interestingly, there is no proof that higher levels of 25(OH)D, can significantly reduce TH1 1,25(OH)2D production. For example, there is a study on sarcoidosis patients whose levels of 25(OH) D were on average 25 ng/ml, and giving them oral vitamin D still resulted in a significant increase of 1,25(OH)2D production. In that study, oral Vitamin D.(100,000 IU) was given to people with and without sarcoidosis. People without sarcoidosis had no change in their 1,25(OH)D levels due to this dose. However, in sarcoidosis patients, this dose caused the 1,25(OH)2D levels to significantly rise, during which 25(OH)D levels rose to almost 50 ng/ml, well past the point at which the MP claims that 25(OH)D starts to block 1,25(OH)2D. But there was no sign of reduced 1,25(OH)2D production from 25(OH)D. Instead, in all patients, an approximate doubling of 25(OH)D levels, resulted in a doubling of 1,25(OH)2D levels, no matter what their initial 25(OH)D levels were.
Similarly, a study on rheumatoid arthritis has shown evidence of TH1 1,25(OH)2D production. This was done by giving patients a single dose of 250 µg of 25(OH)D. Before the dose was given, initial levels of 25(OH)D and 1,25(OH)2D were measured, both in the serum and the synovial fluid of the inflamed joints. These measurements showed that synovial 25(OH)D levels directly correlated with synovial 1,25(OH)2D. This implies that immune cells in rheumatoid arthritis joints are producing 1,25(OH)2D. The study also showed that serum 25(OH)D levels correlated with 25(OH)D synovial levels, which implies that serum 25(OH)D can directly affect immune production of 1,25(OH)2D. However, there was no sign that high serum levels of 25(OH)D were able to suppress TH1 1,25(OH)2D production, as the MP claims. 1,25(OH)D production in the joints increased at the same rate even in patients whose 25(OH)D serum levels were significantly greater than 20 ng/ml. Additionally, serum 1,25(OH)2D were unaffected by 25(OH)D levels. Serum 1,25(OH)2D levels of patients were similar to that of a healthy control group. Thus, there was no evidence that serum 1,25(OH)2D levels were significantly affected by TH1 production of 1,25(OH)2D in rheumatoid arthritis.
Thus, unlike sarcoidosis, the amount of TH1 1,25(OH)2D produced in rheumatoid arthritis is usually not great enough to have a significant effect on serum levels. This is likely true also of other conditions. Sarcoidosis is one of only a few known conditions where TH1 production of 1,25(OH)2D significantly affects 1,25(OH)2D serum levels. This could possibly be due to the location of the disease. Or perhaps it’s due to the type of immune cells that produce the 1,25(OH)2D. In sarcoidosis, the main source of 1,25(OH)2D is believed to be macrophages, while in most other diseases, T cells are believed to be the major source of 1,25(OH)2D.
In any event, there is no evidence that circulating levels of 1,25(OH)2D are affected by inflammation in most of the conditions that the MP claims to treat. However, there are many other influences that can affect 1,25(OH)2D levels, such as a deficiency of calcium. And different factor from s are present in different diseases. In sarcoidosis, 1,25(OH)D serum levels often rise with increasing disease activity, but the opposite is true for rheumatoid arthritis. Therefore, using the D ratio is an invalid way of testing for TH1 1,25(OH)D production. The proper way to test for this, is by administering a large dose of either of vitamin D or 25(OH)D, and then seeing if 1,25(OH)2D levels increase.
When one lowers 25(OH)D levels below 20ng/ml, as recommended by the MP, this will likely increase PTH levels. This is because it’s been found that PTH inversely correlates with 25(OH)D serum levels. The lower the 25(OH)D, the higher the PTH. 20 ng/ml has long been defined by the medical literature to be the lower limit of the normal vitamin D range. This limit was decided, based on where PTH started to significantly rise. However, that limit is most likely much lower than it should have been. Recent research has shown that PTH continues to drop at higher levels of 25(OH)D. This information, combined with results from other studies, has caused many doctors to recommend that 25(OH)D levels should at least be 32 ng/ml.
However, the MP web pages further states that “It is desirable for the D-25 level to be 12 ng/ml or lower”. At this level, PTH levels will be very significantly elevated. Such low levels of 25(OHD are a definite risk for bone loss. In fact, in a case where hyperparathyroidism and sarcoidosis occurred simultaneously, bone loss lab markers were almost reduced to normal after the hyperparathyroidism was treated, even though 1,25(OH)2D levels were still above normal. The researchers concluded that “PTH but not 1,25(OH)2D may primarily be involved in the stimulation of bone turnover.” Indeed, 1,25(OH)2D levels do not appear to be a risk factor for osteoporosis, but low levels of 25(OH)D are associated with an increased risk of osteoporosis.
It is elevated PTH, and not elevated 1,25(OH)2D, which causes bone loss. Many MP pages say the opposite, that 1,25(OH)2D causes bone loss. I.e. “As 1,25-D rises above a certain range (around 43 pg/ml), it stimulates bone osteoclasts, or cells that remove minerals from the bone. Stimulated osteoclasts dissolve bone material, causing it to be reabsorbed into the bloodstream - leading to osteoporosis and osteopenia.” Not only is there no proof that this occurs, but studies have shown that 1,25(OH)2D can actually be used to treat osteoporosis. The MP goes on to say that “Vitamin D does not reverse osteoporosis.” The problem with this statement is that’s it’s based on many studies in which the level of vitamin D supplementation had been too low. For example, they state: “The study of more than 36,000 middle-aged and older women – the largest ever to test the health benefits of vitamin D – found that calcium and vitamin D had essentially no benefit on the bone density of the women involved.” However, the problem with this study is that it only used 400 IU of vitamin D. Such low doses are simply not capable of achieving normal levels of 25(OH)D that are necessary to have an effect on osteoporosis. Thus it’s little wonder that this and other studies have shown little benefit from vitamin D on osteoporosis.
It should be noted that even if one’s PTH levels do not increase as the result of lowering one’s 25(OH)D levels, this doesn’t mean that one is healthy. The tumble level PTH response could be blunted due to other conditions. For example, magnesium deficiency has recently been recognized as a reason for the inhibition of PTH. If your PTH levels aren’t increasing, that could mean that you have a significant magnesium deficiency, which by itself could be the cause of many health problems.
Another reason that PTH levels can be low, is that it is being suppressed, due to excessive calcium serum levels that results from bone loss. This is known to occur in rheumatoid arthritis. In rheumatoid arthritis, PTH and 1,25(OH)2D serum levels have been found to decrease as disease activity increases. A recent study has shown one possible reason for this effect, which is that free serum ionized calcium is elevated in many rheumatoid arthritis patients, and this excess free calcium causes the suppression of PTH and 1,25(OH)2D production. This explanation has been overlooked in the past, because total serum calcium was found to be normal in these patients. However, this is deceiving, because albumin levels are decreased in rheumatoid arthritis, and calcium in the serum is bound to albumin. The reduced albumin levels are most likely caused by the increased inflammatory cytokines. This lack of albumin results in less bound calcium and more free ionized calcium.
In a 2008 article, the MP challenges the new FDA recommendations for increased vitamin D supplementation. That article claims that the new level of 25(OH)D, that vitamin D experts and the FDA are now recommending, is too high, In support of their claim, the article cites a study by Dr. Pollack on the “serum parathyroid hormone concentrations in African American women”. That study found that “a serum concentration of 40–50 nmol/L 25(OH)D is needed to prevent a rise in PTH concentrations in calcium-sufficient African American women in midlife.” This 25(OH)D level is much lower than the 75–80 nmol/L range presently being recommended as the optimal level. However, what the MP article doesn’t mention, is in that study, Dr. Pollack states that “we ultimately reject the clinical utility of the threshold as a way of identifying optimal vitamin D,” Indeed the point of the study was not that the optimum 25(OH)D levels should be lower, but that the optimum level cannot simply be judged by when PTH stops increasing. And in fact, Dr. Pollack states in a later study, that there is an “emerging consensus that 25(OH)D concentrations > 75 nmol/L may be optimal for bone health and extra skeletal effects.”
Dr. Pollack also states that “It is quite possible that African Americans (and others) may require less vitamin D for skeletal health but may require greater intake for prevention of these noncalcemic disorders.” Indeed, 25(OH)D production is affected by pigmentation in the skin For example, according to one article, the “median vitamin D intakes of American blacks are below recommended intakes in every age group, with or without the inclusion of vitamin D from supplements. Despite their low 25(OH)D levels, blacks have lower rates of osteoporotic fractures. This may result in part from bone-protective adaptations that include an intestinal resistance to the actions of 1,25(OH)2D and a skeletal resistance to the actions of parathyroid hormone (PTH). However, these mechanisms may not fully mitigate the harmful skeletal effects of low 25(OH)D and elevated PTH in blacks, at least among older individuals. Furthermore, it is becoming increasingly apparent that vitamin D protects against other chronic conditions, including cardiovascular disease, diabetes, and some cancers, all of which are as prevalent or more prevalent among blacks than whites.”
On the other hand, for other patient groups, PTH levels can be used to support the recommendation for a higher 25(OH)D level. For example, in a study on the “Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy”, it concludes that there is a significant “increase in serum PTH at 25(OH)D concentrations less than 29.8 ng/ml” (74.5 nmol/L). Additionally, there are other parameters that also can be used to support a higher level of 25(OH)D. For example, in a study on glucose metabolism, as measured by HbA1c (A1C), it was found that “There was a nonlinear association between 25(OH)D and A1C: a steep linear decrease in A1C by 25(OH)D until 65 nmol/l and only smaller decreases with further increases”. Also, in a study on healthy postmenopausal women, 1,25(OH)2D levels were shown to fall below 80 nmol/L, The study concluded that for that study group, “the conversion of 25OHD to active vitamin D depends on the substrate concentration”, and that “vitamin D insufficiency should be considered at P-25OHD levels below 80 nmol/L”. Thus, there is definite evidence for the new higher 25(OH)D recommended levels.
The MP article also states that due to vitamin D supplementation, that it is “very difficult to find a population which can be studied in order to ascertain what the level of natural metabolic homeostasis for 25-D might actually be. Two studies do provide a glimpse, however. The first found a high prevalence of vitamin D deficiency in Chilean healthy postmenopausal women. The average level of serum 25-D sampled from 90 healthy ambulatory women showed that 27% of premenopausal, and 60% of postmenopausal women, had 25-D levels under 50 nmol/L. A study showing hypovitaminosis D is common in both veiled and nonveiled Bangladeshi women, found a 25-D level less than 40 nmol/L in approximately 80% of the healthy young women. These studies show a wide variation in levels of 25-D being generated by populations whose diets have probably not yet been significantly altered by ’The Sunshine Vitamin’, indicating that the unsupplemented metabolic homeostasis is probably in the range 23–60 nmol/L, and that it falls with advancing age.”
However, vitamin D researchers have pointed out what’s wrong with this reasoning. For example, Dr. Hollis has written: “Past attempts to define "normal" circulating 25(OH)D were seriously flawed. To properly define "normal" 25(OH)D status in humans, it makes more sense to measure 25(OH)D in "healthy subjects" who are sunbathers, fieldworkers, construction workers, or other individuals who work outside, who are not overly clothed, and who are without sunblock. Humans did not evolve in today’s sun-shy culture, so "normal" with respect to circulating 25(OH)D levels should not be defined by the current average or median population level. In sun-rich environments where clothing or cultural practices do not prevent sun exposure, circulating 25(OH)D ranges from 135 to 225 nmol/L (54–90 µg/L) (1,14,15). Thus, we must be very careful how we define "normal" or adequate or sufficient with respect to circulating 25(OH)D.”
Other studies confirm that high levels of 25(OH)D occur in unsupplemented people in sunny locations. For example, in a Brazilian study, where “the control group consisted of 30 healthy men and the mean age was 34.6 years”, the mean level of 25(OH)D was 82 ± 25 nmol/L". Another study confirms these high levels: In a group of “(49 men and 72 women) aged 17-33 years, mean age 24.7 ± 2.7 years”, “mean serum 25OHD concentration was 78.7 ± 33.1 nmol/L for the group as a whole.” During the summer, the levels reached as high as 97.8 +/- 33.5 nmol/L.
The MP article additionally states the belief that vitamin D studies need to test not just 25(OH)D levels, but also 1,25(OH)2D levels. The MP believes that a low level of 25(OH)D is not necessarily the consequence of insufficient vitamin D, but may actually be due to the downregulation of 25(OH)D, resulting from extra production of 1,25(OH)2D. In support of this theory, they give the following example: “Just a few months ago, a commentary in Journal of Nutrition was uncertain how to explain the results from a comprehensive clinical study showing that at the end of their pregnancies, even though 90% were taking prenatal vitamins, ‘‘vitamin D deficiency’’ was still common in the cohort of pregnant women. The commentary suggested that maybe this might be due to lack of compliance on the part of women in the cohort, or perhaps they just needed even more supplementation than twice the daily reference intake (DRI), the amount they were being given. Surely, when the model fails to describe the data, it is time to question the model, not the data.”
However, it must be noted, that this study was the “first pregnancy study that used the 80-nmol/L cut-point to define vitamin D insufficiency.” It’s no wonder then, that vitamin D insufficiency was found to be common, as the vitamin D supplement in the study was only 400 IU. That dose is the recommended dose based on the older lower level of 25(OH)D from 1997, and would of course be insufficient for many people to achieve the newer level of 25(OH)D. In fact, according to some studies, that dose is insufficient to cause any significant changes in 25(OH)D. For example, to quote one study: “What effect does a daily dose of 400 IU vitamin D for an extended time (months) have in adults? The answer is little or nothing. At this dose (10 µg/d) in an adult, circulating 25(OH)D concentrations usually remain unchanged or decline.” Therefore, much higher doses would be necessary to significantly raise 25(OH)D levels. For example, in the previously mentioned study on African American women, in order to achieve concentrations >75 nmol/L, a dose of 2800 IU was deemed necessary for those with 25(OH)D, >45 nmol/L and a dose of 4000 IU would be necessary for those with a concentration <45 nmol/L. Thus, despite what the commentary in the journal said, there really is no mystery why vitamin D deficiency was still common.
The MP article and web pages claim that low 25(OH)D levels could be “due to the downregulation of 25(OH)D, due to extra production of 1,25(OH)2D.” High levels of 1,25(OH)2D have been shown to be able to suppress production of 25(OH)D. This is a fact that’s been well known since 1984. However, according to one vitamin D researcher, “the physiologic significance of this is not clear”. This researcher points to a study he conducted on phosphate deprivation, which caused an serum 1,25(OH)2D, but did not suppress 25(OH)D levels. Conversely, a study on phosphate ingestion, which decreased 1,25(OH)2D, did not alter 25(OH)D. Many other studies have shown little or no correlation between 1,25(OH)2D and 25(OH)D levels. For example, in a study where ketoconazole was used to block the production of 1,25(OH)2D, 1,25(OH)2D levels decreased from 113 to 70 pmol/L, but 25(OH)D only increased a very small amount, from 52 nmol/L to 55 nmol/L. Also, in a study on Crohn’s disease, patients who had significantly elevated 1,25(OH)2D compared to controls (57.8 vs. 42.1 pg/ml), still only had slightly less 25(OH)D levels (24.2 vs. 27.0 ng/ml). The MP article did not provide any studies to support their claim that extra production of 1,25(OH)2D can play a significant role in decreasing 25(OH)D levels. Presently, it appears that 1,25(OH)2D can only significantly suppress production of 25(OH)D, when levels of 1,25(OH)2D are definitely abnormally high, such as which occurs in sarcoidosis and hyperthyroidism.
The MP article further states: “Arnson et al.(52) noted that ‘‘on the whole, vitamin D confers an immunosuppressive effect’’ in autoimmune disease. That immunosuppression was confirmed by Waterhouse et al.(12) They joined Barnes et al.(50) in noting that correlation between the 25-D and active 1,25-D metabolites seemed strongest in disease, and weakest in health.” The Waterhouse article is written by MP authors, and they used the Vitamin D ratio to support their claim that elevated 1,25(OH)2D production in people was occurring in people who were using the MP treatment. However, no properly matched control groups were used to define what is the “normal” D ratio. In their article, the “normal” D ratio was defined by selecting several studies, neither of which had patients who were matched by gender, age, location, and race, to the people using the MP treatment. Nor was it confirmed that the vitamin D testing procedures were the same, which could be significant, since some tests show less 1,25(OH)2D, while others show more. And, as the MP has pointed out, improper storing of blood samples can reduce observed levels.
As for the Barnes study, this was a study that compared the levels of 25(OH)D and 1,25(OH)2D in male and female multiple sclerosis patients and control volunteers. They found that the absolute values were no different between the two groups. However, while there was a significant positive correlation between 25(OH)D and 1,25(OH)2D, this was only true in females, but not males, which indicates that some sort of gender effect was involved, perhaps unrelated to multiple sclerosis Or, perhaps it is due to a gender effect related to MS, as it has been found that there is renal dysfunction in MS females, but not in males. Thus, it could be that a renal dysfunction plays a role in the production of 1,25(OH)2D in women with MS.
Interestingly, the mean 25(OH)D serum levels of the multiple sclerosis females was 79.1 nmol/L, which is above the range that the MP article claims is normal. And these women were not taking any vitamin D supplements, so this is yet another study that supports the new higher recommended 25(OH)D levels. Additionally, we are surprised that the MP article selected this study to support their views. This is because, the 25(OH)D levels of these women is much higher than the point at which the MP claims that 25(OH)D is supposed to be able to block 1,25(OH)2D production by the immune system. Thus, such high levels should be very significantly suppressing such production, so that very little unregulated 1,25(OH)2D would be present. Any association between 1,25(OH)2D and 25(OH)D at that point would be unrelated to 1,25(OH)2D immune production.
In
any event, it is also worth noting that in another study on multiple sclerosis,
a possible association between low 25(OH)D levels and
MS relapses has been shown: “25(OH)D serum levels were lower and intact PTH (iPTH) serum levels were
higher during MS relapses than in remission. The study was conducted in
As an aside, the MP article also states “Our own work has shown that restoring VDR competence, with a VDR agonist, induces an immunopathologic response when patients suffering from chronic inflammatory diseases are challenged with bacterial protein synthesis inhibitors.” The VDR agonist that is referred to here is the angiotensin receptor blocker Benicar. The MP theorizes that it is also a VDR agonist, but no actual lab study has confirmed this. “Chronically ill subjects, whose conditions have not previously responded to antibiotics, sometimes experience unrestrained immunopathology when a VDR agonist is administered concurrently with the antibacterials. An initial uncontrolled, observational study has shown that recovery often accompanies reduction of the putative bacterial load.” The MP has not presented any data showing that bacteria levels have decreased, nor have they presented a study which shows that “unrestrained immunopathology” is an indication that bacteria are being more effectively killed.
In conclusion, we do not believe that the studies quoted by the MP article, supports the MP’s claim that the new vitamin D recommendations are too high or harmful.
The MP believes that vitamin D is improperly labeled as a vitamin, as it really is a steroid hormone precursor. This is essentially true. However, it is because of this fact, that some vitamin D researchers believe that the normal level of 25(OH)D levels should be much higher than is presently recommended. Quoting from the vitamin D council web page:
“Unlike other steroid hormones, vitamin D has very unusual metabolism in most modern humans, called first-order, mass action, kinetics. All this means is that the more vitamin D you take, the higher the 25(OH)D level in your blood, and the higher the 25(OH)D level in your blood, the higher the levels of activated vitamin D in your tissues. No other steroid hormone in the body behaves like this. Think about it, would you like your estrogen level to be dependent on how much cholesterol you ate? Or your cortisol level?” “No, the body must tightly regulate powerful steroid hormones through substrate inhibition, that is, if an enzyme turns A into B, when the body has enough B, B inhibits the enzyme and so limits its own production.”
“Not so with vitamin D, at least at modern human vitamin D levels.” “Why would the kinetics of vitamin D be different from all other steroids?” “Maybe they are not.” “Maybe vitamin D levels are so low in modern humans that its metabolic system is on full blast all the time in an attempt to give the body all the vitamin D metabolites it craves.” Dr. Hollis has asked, “Is vitamin D's metabolism different in populations in the upper end of 25(OH)D levels (a population of sun-exposed people and a group of women prescribed 7,000 IU per day)? “
According to Dr. Hollis’s study, “vitamin D's kinetics can be normalized, made just like all other steroid hormones in the body, but you have to get enough sunshine or take enough vitamin D to get your 25(OH)D level above 50 ng/ml, and 60 ng/ml would be better. Then your body starts to store cholecalciferol in the body without much further increase in 25(OH)D levels. The reaction becomes saturable. This is a remarkable discovery and it implies levels of 30 and 40 ng/ml are usually not sufficient. It also implies actual vitamin D levels (cholecalciferol levels), not just 25(OH)D levels, may be useful in diagnosing and treating deficiency. Note, that not all of the sun-exposed individuals or women prescribed 7,000 IU/day achieved such levels. That's because the sun-exposed individuals were tested after an Hawaiian winter and because prescribing and taking are two different things. So my answer to "How much should I take if I have cancer?" is take enough to get your 25(OH)D level above 60 ng/ml, summer and winter.”
The fact that PTH levels respond to serum 25(OH)D, points to a fundamental difference in how the medical community views 25(OH)D, versus what the MP believes in. The medical community believes that serum 25(OH)D is very important, while the MP does not. The reason that serum 25(OH)D is believed to be important, is that while serum 1,25(OH)2D affects bone metabolism, many other tissues actually respond to serum 25(OH)D. This is because other tissues contain the enzyme 25(OH)D-1-alpha-hydroxylase, which is capable of converting 25(OH)D to 1,25(OH)2D. This explains why PTH is significantly affected by 25(OH)D levels. The parathyroid gland first converts the 25(OH)D to 1,25(OH)2D, and it then responds to that.
The conversion of 25(OH)D to 1,25(OH)2D occurs in many tissues, as long time vitamin D researcher Professor Reinhold Vieth describes: “Vitamin D nutrition probably affects health beyond just bone. The mechanisms involved in mediating the non-classic (i.e. non-bone) effects of vitamin D are probably, through 1,25(OH)2D produced locally, using circulating, 25(OH)D as the substrate. Many tissues possess, 25(OH)D-1-alpha-hydroxylase, including the skin (basal, keratinocytes, and hair follicles), lymph nodes, (granulomata), pancreas (islets), adrenal medulla, brain, pancreas, and colon. An even wider range of tissues, possess receptors for 1,25(OH) 2D (VDR). All of this reveals a system for paracrine regulation of tissue processes that involves the local production of 1,25(OH)2D. Sufficient vitamin D nutrition, and hence, appropriate 25(OH)D concentration is essential to this local, paracrine role of 1,25(OH)2D that is not generally reflected in the circulating level of 1,25(OH)2D. The paracrine components of the vitamin D endocrine/paracrine systems account for the many effects of vitamin D nutrition and/or UVB light on health and disease prevention.”
It is not surprising that many tissues and cells in the body rely on serum 25(OH)D to obtain 1,25(OH)2D, rather than serum 1,25(OH)2D. 1,25(OH)2D circulates in a very small amount in the serum, and thus may have little ability to affect vitamin D receptors in all tissues. But perhaps more importantly, as we previously saw, serum 1,25(OH)2D levels are heavily influenced by many factors, such as calcium intake, so that it doesn’t make sense that other tissues would be dependent on serum 1,25(OH)2D. By generating 1,25(OH)2D themselves, tissues have the ability to control how much 1,25(OH)2D is present, rather than relying on serum levels. For example, upon stimulation from pathogens, macrophage immune cells upregulate the expression of 25(OH)D-1-alpha-hydroxylase, leading to increased conversion of 25(OH)D to 1,25(OH)2D, which then stimulates the production of the antimicrobial peptide cathelicidin.
Another possibly important role of 25(OH)D, is it’s ability to influence certain forms of cancer. For example, 1,25(OH)2D has been found to inhibit the growth of certain forms of cancer cells, such as in the prostate. However, serum levels of 1,25(OH)2D that are required to achieve significant effects, are often above toxic levels. On the other hand, certain prostate cells are capable of converting 25(OH)D to 1,25(OH)2D. Because of this, it’s been found that 25(OH)D itself, is capable of also inhibiting cancer prostate cell growth, and that the effects are attainable using safe doses of vitamin D.
And regarding studies on vitamin D and cancer, it should be noted that some studies are flawed, in that all they do is to test 25(OH)D levels at a single time, and use that level to see if there is any correlation between vitamin D and cancer rates. These studies are of only limited use, because cancer often develops over many years, so that it’s important to know what the 25(OH)D levels were during those years. Additionally, many cancer studies involving vitamin D supplementation are also flawed, because they have used doses than are lower than are presently being recommended by many vitamin D experts. This is why the study from June 2007, that showed a decrease in all cancers, was so interesting, as it used a relatively high dose of 1100 IU over several years. This study also combined vitamin D with a high dose of calcium, which may be important, as some forms of cancer appeared to respond to a combination of vitamin D and calcium supplementation.
Given the importance of 25(OH)D, it is thus very controversial that the MP claims that 25(OH)D blocks the action of 1,25(OH)2D. According to the vitamin D MP web page: “1,25-D is the only metabolite that turns the VDR on. Everything else turns it off, or at least modifies its capabilities. So exogenous Vitamin D and 25-D both bind into the VDR and block it from working properly. They will displace any 1,25-D from the receptor in a dose-dependent manner. The higher the concentration of Vitamin-D or 25-D competing with the endogenous 1,25-D the more of that 1,25-D will be displaced from the VDR.”
This theory is the basis for the reason of why the MP recommends a low amount of 25(OH)D. It’s not necessarily to lower 1,25(OH)2D levels. It is because they claim that 25(OH)D interferes with the activities of 1,25(OH)2D. This is also the basis of why they claim that 25(OH)D levels have to be low for the vitamin D ratio test to be valid. They believe that 25(OH)D blocks 1,25(OH)2D’s ability to create an adequate TH1 response. A lowered TH1 response would result in reduced inflammation, and reduced inflammation would then mean less 1,25(OH)2D being produced by the TH1 immune system. To quote again from the vitamin D MP web page: “Vitamin D supplementation can increase levels of 25-D high enough to actually shut down the inflammatory production of 1,25-D. When the concentration of 25-D rises above about 25 ng/ml it displaces 1,25-D from the active site in the VDR (Vitamin D Receptor), deactivating the VDR and reducing the body's ability to mount a Th1 immune response”.
However, the medical literature is filled with studies that show that it’s 1,25(OH)2D that has the ability to reduce inflammation, not increase it. In fact, one of such studies is posted on one of the MP’s own web pages. If 25(OH)D could block the effects of 1,25(OH)2D, then according to the medical literature, that would cause an increase in inflammation, not a decrease.
The claims by the MP, of the effects from 25(OH)D and 1,25(OH)2D, drastically opposes the fundamental viewpoints of many vitamin D researchers. To understand their views of vitamin D, I highly suggest you click here to read a chapter in a book on vitamin D, that was written by long time vitamin D researcher Professor Reinhold Vieth. Any unreferenced statements that I make in the following paragraphs are taken from that chapter.
Firstly, the levels of 25(OH)D which results from supplemental vitamin D, at the dose which is recommended in the US, is much lower than that which can be produced from sunshine. The highest claimed safe oral dose (which few people take) is 2000 IU. However, sunshine can create up to 5 times that amount. The current US RDA for vitamin D, for adults under 50, is only 2% of what a person with white skin can naturally produce in 20 minutes of summer sun. Thus, “natural” production of vitamin D, according to the theory on the MP web pages, would severely affect VDR activity much much more than oral sources. However, there are no studies that show that this happens. If inactive forms of vitamin D were able to affect VDR activity, it would affect serum calcium levels, and the body would then have to offset that by changing the levels of 1,25(OH)2D levels. But this does not happen. Inactive levels of vitamin D can vary significantly, but under normal circumstances, active levels will usually stay the same.
Secondly, no study that I’ve yet found, mentions that inactive forms of vitamin D adversely affects VDR functioning. Unmetabolized vitamin D has not been found to directly affect the VDR, in a study on the effects of different forms of vitamin D on calcium absorption And in molecular studies on VDRs, the binding ability of 25(OH)D is believed to be 500 times lower than 1,25(OH)2D. In another article, that number is quoted as being 1000 times lower. On the other hand, the amount of 25(OH)D in the blood stream is hundreds times greater than active D, which might lead one to speculate that this greater amount of 25(OH)D might offset it’s lower binding ability. making 25(OH)D just as likely to attach to VDRs. However, this is not totally the case, because in that same article, it’s pointed out that 25(OH)D is much more tightly bound to proteins in the plasma, by a factor of at least 10. Not only that, but the storage capability in plasma for vitamin D is huge. Unlike many other steroids, such as glucorticoids, where the binding proteins circulate at the same order of magnitude as the steroids themselves, the vitamin D binding protein circulates at a level that is 50 times more than the vitamin D metabolites themselves. Thus, under normal situations, the bloodstream is meant to store lots of 25(OH)D.
The body’s processes that handle vitamin D, appear to be much better suited for handling excess amounts of vitamin D, than a deficiency. This is likely due to the fact that our ancestors were out in the sun for much longer periods of time, with less clothing, and in tropical zones, so that the body had to deal with large amounts of vitamin D production, rather than a limited amount. Large amounts of vitamin D production can be easily handled. However, when toxic levels do occur, such as due to intoxication, Vieth has theorized that it’s the 1,25(OH)2D which is the source of toxic side effects such as hypercalcemia, and not the 25(OH)D. This is because the 25(OH)D binds more easily to the binding protein in the plasma blood, and this then leaves less amounts of the protein for 1,25(OH)2D to bind to. The unbound “free” amount 1,25(OH)2D in plasma increases, making it more available to VDRs in tissues. This theory has been confirmed in a study on patients with vitamin D toxicity, where the level of free vitamin D was found to be significantly increased, due to excessive amounts of 25(OH)D.
Given the strong binding ability of 1,25(OH)2D on VDRs, and that 25(OH)D levels can be easily increased due to natural production, most researchers do not credit 25(OH)D with being able to significantly affect VDRs. In fact, in a study on sarcoidosis, radioactive 1,25(OH)2D was bound to VDR receptors on T-lymphocytes (T cells), and it was found that 25(OH)D was unable to displace it, yet it could be displaced by normal 1,25(OH)2D. “Lavage T-lymphocytes from patients with tuberculosis or with sarcoidosis, but not those from normal control subjects, expressed 1,25(OH)2D3 receptors as demonstrated by binding of [3H]1,25(OH)2D3, which was inhibited by the presence of excess unlabeled 1,25(OH)2D3, but not by the presence of unlabeled 25(OH)D3.” Thus, this does support the theory that 25(OH)D can displace or block the effects of 1,25(OH)2D.
The MP claim about 25(OH)D could be easily tested for, and probably should have been noticed by at least one study in the medical literature by now, as it would be appear to be a fundamental effect of 25(OH)D. For example, if 25(OH)D blocks 1,25(OH)2D stimulation of VDR, then PTH should be stimulated, not suppressed by 25(OH)D, as 25(OH)D would be blocking the suppression effects of 1,25(OH)2D. As another example, it’s known that 1,25(OH)2D can reduce rheumatoid arthritis symptoms. But 25(OH)D doesn’t appear to block these effects of 1,25(OH)2D, as shown by the fact that increased 25(OH)D levels are also associated with reduced symptoms rather than less. There are multiple such examples in the literature. For example, in a test on super high doses of vitamin D for multiple sclerosis (from 28 000 to 280 000 IU/wk), 25(OH)D reached twice the top of the physiologic range, yet there were no adverse effects. If 25(OH)D really does block 1,25(OH)2D at lower levels, then such high doses of 25(OH)D surely should block almost all 1,25(OH)2D activity, with dire effects. Instead, this study concluded that “vitamin D intake beyond the current upper limit is safe by a large margin.”
The only proof that the MP has presented for their theory that 25(OH)D blocks 1,25(OH)2D, is a computer simulation. However, no actual lab studies have been presented. In fact, on the MP discussion web page, when a person asked for a real study that shows that 25(OH)D is an antagonist to the VDR and blocks 1,25(OH)2D, the response was “I just can't recall any single paper which shows that, as it is a pragma which forms the underpinning of all the drug discovery in Vitamin D analogs, and has been proven many, many times by individual drug discovery groups.” However, this is not true. Indeed, an analog of 25(OH)D has also been shown to be a Vitamin D agonist analog. In fact, if 25(OH)D has significant antagonistic effects on the VDR, then it would be especially useful for Paget's disease, where hypersensitivity to 1,25(OH)2D occurs, and research is ongoing to develop effective VDR antagonists. Unfortunately, true VDR antagonist are much rarer than VDR agonists.
For more information about vitamin D, I highly suggest to click here to read the information on the Vitamin D council site.
The MP’s original claim about vitamin D, was that excess production from 1,25(OH)2D in sarcoidosis is a major cause of the inflammation. Indeed, a few researchers have hypothesized that 1,25(OH)2D might play a significant role in granulomas formation. This is mainly based on the fact that 1,25(OH)2D has the ability to promote the creation of immune cells that granulomas are created from. If this theory was found to be true, then that would at least explain why the MP works for sarcoidosis. But that explanation would not apply to other conditions that don’t involve granulomas. Granuloma formation is a complex immune process that is more than just a group of white cells. One cannot generalize what the effects of 1,25(OH)2D will be for any given condition, based on what its effects are on sarcoidosis. Indeed, even other granulomatosis diseases may respond differently to 1,25(OH)2D, as exemplified by the fact that 1,25(OH)2D has been found to be beneficial for tuberculosis.
But whatever the effects of 1,25(OH)2D are, the fact is, that the medical literature doesn’t yet support the belief that 1,25(OH)2D can significantly affect the progression of sarcoidosis. For example, drugs such as ketoconazole, that are able to lower the production of 1,25(OH)2D, have been given to sarcoidosis patients. However, while they are able to reduce the elevated 1,25(OH)2D levels, and decrease hypercalcemia, there is no evidence that they can control any of the other symptoms in sarcoidosis, or the course of the disease. Additionally, lab tests have shown that granuloma formation can occur even in animals lacking the vitamin D receptor (VDR). In fact, the granulomas formed in such animals, were actually significantly larger than in normal animals. Thus, even though elevated vitamin D has known to be associated with sarcoidosis for almost 2 decades, no study has yet proven that 1,25(OH)2D is a major cause of the chronic inflammation seen in sarcoidosis.
In any event, the main focus of the MP these days is with regard to 25(OH)D, as they believe that it blocks proper stimulation of the vitamin D receptor (VDR). However, the MP also believes that 1,25(OH)2D is also bad, in that it overstimulates the VDR, and allows the CWD bacteria to either enter immune cells or hide from the immune system. Unfortunately, the latter claim can’t easily be proven, because CWDs aren’t not easily detected. First, it has to be proven that CWDs are significantly present in the conditions that the MP treats, and then it has to be proven that 1,25(OH)2D effects them. Neither of these has yet been proven.
On the other hand, the medical literature is now starting to document the fact that vitamin D has infection fighting properties. This has long been suspected, given the long held belief that sunshine helps with treat tuberculosis. New studies have shown that vitamin D supplementation can help treat tuberculosis. The receptor TLR2 on immune cells responds to tuberculosis mycobacterium, which causes an increase in VDR expression and 1,25(OH)2D production, leading to increased levels of the cathelicidin antimicrobial peptide (LL-37), which is capable of killing tuberculosis mycobacterium.
Note, however, that no proof has been shown that 25(OH)D blocks this process. Indeed, the addition of 25(OH)D has been shown to improve the production of LL-37. This is because, as the study showed, the rate of conversion of 25(OH)D of 1,25(OH)2D is upregulated by the stimulation of the TLR2 receptor, in order to provide sufficient levels of 1,25(OH)2D. Furthermore, the study found that “African Americans have significantly decreased serum 25(OH)D3 levels and are known to have increased susceptibility to M. tuberculosis infection, as well as more rapid and more severe course of disease. We observed that serum levels of 25(OH)D3 in African Americans were significantly lower than in a Caucasian cohort. Strikingly, when these serum samples were used to support TLR2/1 activation, the induction of cathelicidin mRNA was significantly lower in the presence of serum from African American than the Caucasian individuals. Finally, supplementation of the African American serum with 25(OH)D3 to a physiologic range restored TLR induction of cathelicidin mRNA.”
MP web pages have declared that the VDR Nuclear Receptor is at the heart of human innate immunity. While VDR activation has been shown to increase production of LL-37, this only occurs in epithelial cells. Not only that, but it only occurs in certain epithelial cells. For example, it does not occur in colon epithelial cells. Additionally, other processes are capable of producing LL-37, without the help of the VDR. And while LL-37 does have potent antimicrobial properties, many bacteria have developed methods to avoid the effects of LL-37.
However, the MP still does consider excess 1,25(OH)2D to be a problem. To quote from one web page: "In order to induce recovery from chronic inflammatory disease, it is necessary to restore VDR functionality by removing all exogenous sources of the secosteroid we call ‘Vitamin-D’, and dampen down over-exuberant VDR activity, for example with the ARB Olmesartan. This enables the immune system to recognize the pathogens.”
However, any belief that 1,25(OH)2D blocks the body’s ability to fight infections, is not well supported by the medical literature. For example, a study on using 1,25(OH)2D to prevent graft rejection, showed that "1,25-Dihydroxyvitamin D3 prolongs graft survival without compromising host resistance to infection or bone mineral density”.
I also did a thorough search for any studies in PUBMED that showed detrimental effects from 1,25(OH)2D on infections, and I could find very few studies. In one study, turkeys whose immune systems were artificially depressed by corticosteroids, were given 1,25(OH)2D supplementation, and then exposed to E. coli infections. Higher mortality rates occurred due to this 1,25(OH)2D supplementation. This is not too surprising, as combining 1,25(OH)2D and corticosteroids is known to have additive immunosuppressive effects. And since this situation was a TH2 immunosuppressed condition, it has little relevancy for a TH1 condition. Interestingly, a previous study showed that normal vitamin D supplementation, under the same immunosuppressive conditions, had beneficial effects against the E. coli infections. Thus, under normal circumstances, vitamin D intake would be useful for such an infection. This shows the problems with many lab studies regarding the immunosuppresive effects from 1,25(OH)2D, versus real situations that involve vitamin D supplementation.
The production of hormonally
active 1,25(OH)2D involves several steps.
It starts with the unmetabolized form of vitamin D which is in
supplements and foods, and which is also created in the skin due to sunshine
exposure. Once in the body, it is either
stored in tissues, eliminated from the body, or metabolized by the liver into
25(OH)D. 25(OH)D binds to a protein and
circulates through the serum and tissues.
As an aside, several MP web pages make the mistake of claiming that all
of the vitamin D is metabolized and stored as 25(OH)D. This is incorrect. It is the unmetabolized vitamin D which is stored in various
tissues in the body 25(OH)D only lasts in the body for about 2-3 weeks. Unmetabolized vitamin D lasts for several
months. The latter is used as a source
of vitamin D by the body during the winter, in areas where the sun is not high
enough to stimulate vitamin D production (i.e. which includes about half the
25(OH)D is mainly converted into the hormonally active metabolite 1,25(OH)2D. This primarily occurs in the kidneys, where it's used to control calcium levels. 1,25(OH)2D usually lasts in the body for less than a day. Many other tissues can also convert 25(OH)D to 1,25(OH)2D. This non-renal production is believed to be used for local tissue effects. It usually results in the production of much smaller amounts of 1,25(OH)2D, compared with renal production. Such extrarenal production usually does not contribute much to serum levels, except in conditions such as sarcoidosis.
It’s recently been found that 1,25(OH)2D can also be directly created in the skin due to sunshine. The MP uses this fact to support their claim that “any and all 25-D which is made from sunlight is energetically converted to 1,25-D” The MP believes that this production is upregulated in TH1 conditions, such that “sunlight is not usually a significant contributor to the 25-D levels of Th1 patients.”
But the researchers who discovered that the skin could directly produce 1,25(OH)D, do not believe that this process could result in a significant amount of 1,25(OH)2D. Instead, in the conclusion of the study, they stated that “the photoproduced 1,25(OH)2 D3 quantities in vitro are very minute though. We measured 1,25(OH)2 D3 quantities of 175-177 fmol/106 cells in cellular homogenates and medium of BM15766-pretreated cells after UVB irradiation.” “This implies that only 0.005% of the intracellular 7-DHC is converted into 1,25(OH)2 D3” “cutanous 1,25(OH)2 D3 photoproduction probably does not contribute to the systemic effects of 1,25(OH)2 D3 . Indeed, the low 1,25(OH)2 D3 levels in hepatectomized or nephrectomized animals suggest that epidermal 1,25(OH)2 D3 production cannot compensate for the lost 1-hydroxylase activity in these animals and therefore that epidermal 1,25(OH)2 D3 photoproduction maximally accounts for a small fraction of total systemic 1,25(OH)2 D3 levels.”.
One of the researchers who authored that study, is Professor Roger Bouillon. He has been studying vitamin D since the 1970s, and is a strong believer that vitamin D deficiency is a wide spread problem. In fact, he has recently stated his belief that over one billion people may be suffering from a vitamin D deficiency.
The small production of 1,25(OH)2D in the skin, is likely there to create a local effect, such as protecting the skin against the damages of sunshine exposure. Localized production of vitamin D is a common scenario in the body. 1-hydroxylase, the enzyme that creates 1,25(OH)2D, has been found in many different tissues in the body. However, there is no study to support the claim that the activity of this enzyme is up regulated in the skin in TH1 conditions. In fact, one study that did measure the skin levels of 1-hydroxylase in sarcoidosis, did not find elevated levels. According to that study, in skin from patients with sarcoidosis, “1-hydroxylase was normally expressed in basal keratinocytes of the epidermis.”
Some people on the MP who avoid sunlight and wear sunglasses for a long period of time, and who then develop rapid negative symptoms when they are then exposed to the sun, often attribute this due to 1,25(OH)2D production. It is a fact that healthy people with lower 25(OH)D and 1,25(OH)2D levels, will produce greater amounts of 25(OH)D and 1,25(OH)2D, when exposed to either sunlight or vitamin D supplementation, compared to people with higher levels of 25(OH)D and 1,25(OH)2D. Thus, the lower your 25(OH)D levels, the more sensitive one will be to the effects of sunshine and vitamin D. Therefore, it’s not surprising that people who avoid sunlight and vitamin D, will become more sensitive to it’s effects.
Also, we have read several other statements on that MP web site, that are also incorrect regarding the ability of sunshine to produce vitamin D. For example, one web page states that people can get sufficient amount of vitamin D via sunshine, “in only a fraction of the amount of time they spend driving each week." However, this is not so, as a study has shown that when driving in a car with one’s windows closed, in direct sunshine, only 11% of the sun’s ultraviolet rays are able to get through. When the car is in shade, 0% gets through. Thus, people in a car, are exposed to a very limited amount of the sun rays that are necessary to produce of vitamin D.
Even if one does not have an elevated vitamin D ratio, the MP believes that having a bad reaction to Benicar, means that you have a TH1 dominant condition, and that you can then be treated by the MP. The MP believes that Benicar has almost no side effects in normal people, and so that any bad effect is due to the body reacting to bacteria dying off, and that these bacteria are the real cause of TH1 conditions. This method of using of Benicar to diagnose a TH1 condition is described by the MP as a “therapeutic probe”. To quote one MP web page: “A therapeutic probe is a method of determining a diagnosis that might be difficult to decide by other means.” “For example, if someone has pain in their great toe but blood tests are nonconclusive, the doctor may have the patient take a medication for gout. If the pain goes away, the patient is presumed to have gout and the medication is continued to prevent future episodes.”
However, there are several problems with these statements. First, the term "therapeutic probe" is not a standard medical term. In fact, the term is only found on a handful of web pages on the whole internet, and on just about all of them, the term is used to refer to a real physical probe. Secondly, the analogy with gout is flawed, due to the fact that in the case of the MP, a negative effect is expected from the medicine, while in the case of gout, a positive benefit is expected. Giving a medicine to see if a person will get better from it, and then continuing that medicine due to the fact that a positive benefit occurred, is of course extremely common. However, giving a medicine specifically to see if a person will get worse from it, and then continuing that medicine because this occurred, is quite rare. While it’s true that many medicines will first cause side effects before the positive benefits occur from it, these side effects are almost never considered to be a sign that the medicine is the proper medicine to use to treat a person.
And lastly, the gout example is simply wrong. Gout attacks are treated using normal anti-inflammatories, not gout specific medicines. Gout specific medicines are only useful to prevent gout attacks. However, since gout attacks often takes months or years to reoccur, one would have to use gout medicine for a very long time, before seeing the results. Thus, this is not a practical way in which gout is diagnosed. Instead, gout is diagnosed by taking samples of the synovial fluid of the joint, and by excluding other possible diagnoses based on other lab tests and symptoms.
In any event, the MP states that “persons without TH1 inflammation would note only a mild reduction in blood pressure if they took Benicar 40mg every eight hours. A positive response to a therapeutic probe with the Benicar blockade would be any reaction, either a reduction in symptoms or an increase in symptoms.” However, there is no proof that a lowering of blood pressure is the only thing that will happen to healthy people at such a high dose. Benicar has not been studied at this dose in either healthy people, or people with inflammatory diseases. Even at lower doses, many negative effects from Benicar have been reported by people taking Benicar for hypertension. Headaches, chest pain, muscle pain, and coughing, are just a few of the side effects that people experienced. However, when these same effects are experienced by people on the MP, they are explained as being reactions to bacteria dying off, and that experiencing these symptoms indicates that the person has a TH1 condition.
Many of the side effects from Benicar are due to the effects of blocking angiotensin II, and the decrease in aldosterone levels. These changes can lead to a decrease of blood pressure and volume, which can aggravate orthostatic related problems. People with CFS and fibromyalgia are prone to having orthostatic problems, and they may experience symptoms from Benicar that other people may not experience.
Benicar can significantly lower aldosterone. Decreased aldosterone can cause fatigue, headaches, muscle weakness, and constipation, all symptoms that have been reported by people on the MP who have taken Benicar. People who are prone to dehydration, or who have kidney problems, are more susceptible to symptoms that result from decreased aldosterone levels. Also, certain drugs can inhibit the production of aldosterone, and thus could potentiate the effects of Benicar. For example, some NSAIDS can reduce aldosterone levels. Potassium channel blockers, such as the anti-diabetic drug glyburide, can also block inhibit the production of aldosterone. Thus, ARBs may be able to lower kidney functioning in people who are susceptible to this problem. This may especially be true, given the very high doses of Benicar that are used by the MP.
However, it should also be noted that the effect of ARBs on aldosterone levels can be highly variable, and often such an effect can take many weeks and months before it occurs. In a study on long-term use of an ARB, aldosterone decreased in about half the patients, while in the other half it increased. This increase occurred due to an effect known as “aldosterone escape” or “aldosterone breakthrough”, where the body uses other ways to produce aldosterone. For ARBs,