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Take or avoid vitamin D supplements?


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279 replies to this topic

#1 pres

Posted 13 January 2008 - 10:41 PM


My plans to take vitamin D seemed well funded (lots of positive research these days about high vitamin D levels) and then I stumbled upon this article that promotes the views of Trevor Marshall.

"The Truth About Vitamin D: Fourteen Reasons Why Misunderstanding Endures", by Amy Proal (a biologist), 15/09/2007
http://bacteriality....09/15/vitamind/



The article strongly advises against vitamin D supplementation and contains unusual allegations like these (I've tried to summarize, most of this is not literally from the article):

- 25-D becomes increasingly immunosuppressive starting from levels around 20 ng/ml. Therefore supplementation will damage your health in the long run.

- As a person falls ill with a chronic disease, L-form bacteria begin to live inside the cells of the immune system and in various tissues. These bacteria create proteins that, just like elevated 25-D, are able to bind and block the Vitamin D Receptor and block the ability of the Vitamin D Receptor to turn on the immune system.

- Chronically ill people are not deficient in vitamin D, they often have low 25-D but high 1,25-D.

- To cure many of these chronic diseases vitamin D has to be avoided and low-doses antibiotics have to be used (the "Marshall Protocol" http://www.marshallprotocol.com/ )

- Much vitamin D supplementation research is useless as it doesn't investigate both 25-D and 1,25-D levels and tends to cover only the short run, during which vitamin D provides short term relief with a decrease in toxins, cytokines, and overall inflammation, because it shuts down the immune system. As it shuts down the immune system vitamin D makes people sicker in the long run as the immune system doesn't do its job anymore and L-form bacteria accumulate.



There are a lot of references, but as a lay person it's difficult for me to validate them.




Slides with text and references by Marshall:
http://autoimmunityr..._bio21_2006.pdf


This stuff really goes against mainstream opinion.
But then again, mainstream opinion has been wrong before.

Trevor Marshall isn't a medical doctor.
But then again, neither is Aubrey de Grey.

I'm wary of documents titled "The truth about..." and of theories that offer a simple explanation and cure for a whole bunch of diseases.
But then again, what if even part of what he says is correct?

Wikipedia is relatively positive about Marshall, but the neutrality of the article is disputed. It does mention: "Observations that the Marshall Protocol successfully treats certain autoimmune diseases have yet to be fully validated by the medical community. Rosen and Bagwell, in their 2007 review of treatments for sarcoidosis, argue that the Marshalls' 2003 paper, "Antibiotics in sarcoidosis—reflections of the first year" has "serious deficiencies" claiming that the data are not peer-reviewed and that results are not quantified."
http://en.wikipedia....Trevor_Marshall

Edited by pres, 13 January 2008 - 10:45 PM.

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#2 Re: Take or avoid vitamin D supplements?

Posted 13 January 2008 - 11:57 PM

Here is one study exploring a correlation between brain lesions and high vitamin D intake:
http://winmlm.neostr...rainLesions.pdf
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#3 kclo4x Re: Take or avoid vitamin D supplements?

  • Location:USA

Posted 13 January 2008 - 11:59 PM

Well, that is disturbing! I more or less thought the more vitamin D the better because of this artical that you guys have probably already have seen.

http://www.nutraingr...elated-diseases


"Live longer with vitamin D, study says
By Alex McNally


Vitamin D may help slow down the ageing process, scientists have found, adding further weight to the importance of adequate intake of the vitamin.


Researchers from King's College, London, measured telomeres - part of a chromosome which shortens with age - in more than 2,000 women and found those who had higher levels of the vitamin in their body had longer telomeres.

Writing in the American Journal of Clinical Nutrition, the scientists looked at 2,160 women aged 18 to 79 years and measured leukocyte telomere length (LTL). LTL is a predictor of ageing-related disease and decreases with each cell cycle and increased inflammation, the scientists said.

Scientists measured concentrations of 25-hydroxyvitamin D (the 'storage' form of vitamin D) and found a link between increased concentrations and telomere length.

They found that after taking into account the age of the volunteer, women with higher levels of vitamin D were more likely to have longer telomeres.

They wrote: "The difference in LTL between the highest and lowest tertiles of vitamin D was 107 base pairs, which is equivalent to five years of telomeric ageing. This difference was further accentuated by increased concentrations of C-reactive protein, which is a measure of systemic inflammation."

The team concluded that higher vitamin D concentrations, which are "easily modifiable through nutritional supplementation", are associated with longer LTL, which underscores the potentially beneficial effects of vitamin D on ageing and age-related diseases.

Lead researcher Dr Brent Richards said: "These results demonstrate for the first time that people who have higher levels of vitamin D may age more slowly than people with lower levels of vitamin D.

"This could help to explain how vitamin D has a protective effect on many ageing related diseases, such as heart disease and cancer. Further studies are required to confirm these findings."

They also found that out of the women tested, 700 already took vitamin D supplements, and had longer telomeres than those who did not.

However, the scientists gave no indication of what levels of supplementation would be needed to achieve these results.

The scientific community has already called for an increase in the recommended level of vitamin D intake.

Currently, the recommended daily intake is set at 400 IU, and the tolerable upper intake level (UL) in Europe and the US is set at 2000 International Units (IU), equivalent to 50 micrograms per day. Research, particularly from clinical trials, suggests that this should be raised.

A recent risk assessment by the US-based trade organisation, the Council for Responsible Nutrition (CRN) concluded that the UL could be raised to 10,000 IU (250 micrograms per day).

Vitamin D refers to two biologically inactive precursors - D3, also known as cholecalciferol, and D2, also known as ergocalciferol. The former, produced in the skin on exposure to UVB radiation (290 to 320 nm), is said to be more bioactive. The latter is derived from plants and only enters the body via the diet.

Both D3 and D2 precursors are hydroxylated in the liver and kidneys to form 25- hydroxyvitamin D, the non-active 'storage' form, and 1,25-dihydroxyvitamin D, the biologically active form that is tightly controlled by the body."



Also I have heard that some bacteria is good for you, perhaps if vitamin D really is a significant
immunosuppresant, it may benificial. Fruit flys exsposed to germs out live (or maybe it was that they were just heatheir?) then the fruit flies that lived in a sterile enviroment. Also, Rats exsposed to soil bacteria do better on the anti-depressant tests. But i guess it may not be the same thing?

Edited by kclo4x, 14 January 2008 - 12:04 AM.

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#4 gavrilov Re: Take or avoid vitamin D supplements?

  • Location:Chicago, USA

Posted 14 January 2008 - 04:57 AM

Thank you for interesting links and discussion. The key issue here may be the dose of vitamin D.

Some doctors believe that the recommended dose of vitamin D should be about 400 IU, and no more than 2,000 IU per day.

This is because the body can store vitamin D, making it possible for the vitamin to build up top toxic levels (see page 109 at: http://tinyurl.com/2t6jcv).

Hope it helps,

-- Leonid Gavrilov, Ph.D.
Website: http://longevity-science.org/
Blog: http://longevity-science.blogspot.com/
My books: http://longevity-science.org/Books.htm
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#5 ortcloud Re: Take or avoid vitamin D supplements?

Posted 14 January 2008 - 05:37 AM

You may want to email Krispin and ask her about this article. She takes a while to answer emails but
will get around to it.
Regarding Trevor, he is generally not one you can talk to, he doesnt reason or discuss anything that
challenges his position. I posted something on his board regarding immune modulation and he couldnt
handle it and deleted the post and banned my account along with other people who asked him. He is
out for fame and glory and my post basically threatened his therapy and if that happened all of his
worshippers and disciples might leave his cult. Cult leaders generally dont like to have their message
challenged. so you see he crossed a line where he has put his power above the truth. When you do
that you have to be very careful what he says. It is instinct to defend ones beliefs and reject incongruencies
in ones beliefs despite them having merit and truth. Basically a cognitive dissonance kind of thing.
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#6 krillin Re: Take or avoid vitamin D supplements?

  • Location:USA

Posted 14 January 2008 - 08:44 AM

These Marshall Protocol guys are suffering from monomania and are clearly out of their depth. I read through the links in this thread and didn't find a single mention of the role of vitamin K in preventing calcification. And some of their arguments are just plain goofy.

On page 5 Waterhouse says that there used to be more forests when we evolved, so UV exposure was lower. We didn't live in the forests, you numbskull, we chopped them down and lived in the clearings! Bears and wolves lived in the forests.

Amy Proal's site is sloppy. Reference #77 is obviously not the paper she intended to cite. And how can you take seriously someone who says "Another misconception among some clinicians is the idea that vitamin D enhances the absorption of calcium. This is not the case."? There's also a lot of jumping to conclusions, like

Not surprisingly, the researchers, who failed to question the subjects’ levels of 1,25-D, picked up on the fact that patients at a higher risk for colorectal and breast cancer had lower levels of 25-D. In reality, the low 25-D observed in the subjects resulted from the downregulation of 25-D under the influence of elevated levels of 1,25-D.

How does she know what their 1,25-D levels were?

Amy should be really embarrassed by this paragraph.

On the tanning website, tantoday.com, Jeffrey Dach, MD, laments in his article “Vitamin D Deficiency, the Ignored Epidemic” that the majority of people living in “sunny Florida” showed vitamin D deficiency (less than 20 ng/ml), or insufficiency (less than 40 ng/ml).41 This seems odd, considering the fact that if a person spends only 8-10 minutes in the sun they will obtain the entire RDA requirement for vitamin D even if they are not consuming foods with vitamin D or fortified products.

If she had even a minimal comprehension of the literature, she would know that the vitamin D RDA can't prevent deficiency.

Look at this bilge. On pages 15-16 Marshall says (without a shred of evidence) that vitamin D fortification is what makes Americans fat! The opposite appears to be the case.

More than half of the obese children had vitamin D levels <20 ng/ml with equal gender distribution. Vitamin D insufficiency was associated with increased age, BMI, and SBP, and decreased HDL-C.

Here's a good debunking website. It shows that 25-D won't suppress immunity. Marshall and his cronies claim that 20 ng/ml will antagonize the vitamin D receptor, but as far as I know, he only has his molecular model as evidence.

Figure 6 summarizes why it's best to have a 25-D of at least 36-40 ng/ml. I've seen anecdotes of harm from 65 ng/ml, and 80 ng/ml is generally considered to be toxic.
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#7 maxwatt Re: Take or avoid vitamin D supplements?

  • Location:New York

Posted 14 January 2008 - 04:08 PM

To D or not to D; that is the question.
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#8 bran319 Re: Take or avoid vitamin D supplements?

Posted 14 January 2008 - 08:17 PM

Even if these claims have any truth to them, I don't see what relevance this has to a healthy individual.
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#9 krillin Re: Take or avoid vitamin D supplements?

  • Location:USA

Posted 14 January 2008 - 10:06 PM

Even if these claims have any truth to them, I don't see what relevance this has to a healthy individual.


They think that everyone is infested by these bacteria and that vitamin D will allow them to thrive over time and ultimately give you some disease.
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#10 sUper GeNius Re: Take or avoid vitamin D supplements?

  • Location:Phila PA USA Earth

Posted 15 January 2008 - 01:13 AM

Even if these claims have any truth to them, I don't see what relevance this has to a healthy individual.


They think that everyone is infested by these bacteria and that vitamin D will allow them to thrive over time and ultimately give you some disease.


http://www.cbsnews.c...in3684138.shtml

"The incidence of internal cancers -- colon, lung, breast, and prostate -- also increased from north to south. But Setlow's team found that those who lived in southern latitudes -- and who made more vitamin D from sun exposure -- were much less likely to die from those cancers than were the northern latitude residents.

"Vitamin D reduces the death rate from internal cancer," Setlow tells WebMD."

What I want to know is, why were the cancer rates higher the further they went south??
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#11 ajnast4r Re: Take or avoid vitamin D supplements?

  • Location:Sacramento, California

Posted 15 January 2008 - 01:48 AM

why would a single article make you question a WEALTH of positive evidence? vitamin D is perhaps the most well studies vitamin, and the only one that modern science pretty much agrees SHOULD be supplemented for its health benefits.

Edited by ajnast4r, 15 January 2008 - 01:48 AM.

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#12 lucid Re: Take or avoid vitamin D supplements?

  • Location:Austin, Tx

Posted 15 January 2008 - 02:06 AM

It is also worth mentioning that it is almost impossible to OD on vitamin D. To show signs of overdosing you need to consume about 40,000 UI. A fairly good though onesided review of safety of vitamin D.
http://www.ajcn.org/...t/full/69/5/842

For adults, the 5-µg (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers, osteoarthritis progression, multiple sclerosis, and hypertension. Total-body sun exposure easily provides the equivalent of 250 µg (10000 IU) vitamin D/d, suggesting that this is a physiologic limit. Sailors in US submarines are deprived of environmentally acquired vitamin D equivalent to 20–50 µg (800–2000 IU)/d. The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response that is surprisingly flat up to 250 µg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 µg (4000 IU)/d is required. Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 µg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of >=1000 µg (40000 IU)/d . Because vitamin D is potentially toxic, intake of >25 µg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 µg (2000 IU)/d is too low by at least 5-fold.


In 2005, scientists released a metastudy which demonstrated a beneficial correlation between vitamin D intake and prevention of cancer. Drawing from a meta-analysis of 63 published reports, the authors showed that intake of an additional 1,000 international units (IU) (or 25 micrograms) of vitamin D daily reduced an individual's colon cancer risk by 50%, and breast and ovarian cancer risks by 30%.
http://www.ajph.org/...stract/96/2/252

Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk.

The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects.

The authors of this study recommend 1000 UI at a population wide level. I feel very comfortable with my 5,000 UI / day supplementation. (I would probably supplement a little bit less but I weigh 230)

There was also a thread recently showing that Vit D decreases heart disease risk: http://www.imminst.o...ead-t19787.html

Edited by lucid, 15 January 2008 - 02:08 AM.

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#13 krillin Re: Take or avoid vitamin D supplements?

  • Location:USA

Posted 15 January 2008 - 08:33 PM

What I want to know is, why were the cancer rates higher the further they went south??


In Figure 4 they added more countries and the internal cancer rate vs latitude graph turned into a scatter plot. So sun exposure can't explain it.

Looking at Figure 2 again, which is the basis for the claim of higher internal cancer incidence in the sunnier countries, as someone in the physical sciences I would be too ashamed to draw most of those lines.
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#14 krillin Re: Take or avoid vitamin D supplements?

  • Location:USA

Posted 15 January 2008 - 08:49 PM

A fraction of the population can get an overdose from a few thousand IUs, so get blood tests if you take more than 1000 IU. 1000 IU got me to 45.1 ng/ml.

http://books.nap.edu...i...76&page=282
http://www.annals.or.../full/127/3/203
http://sunlightandvi...Sample Chapters
http://www.westonapr...indmiracle.html
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#15 lucid Re: Take or avoid vitamin D supplements?

  • Location:Austin, Tx

Posted 15 January 2008 - 08:53 PM

What I want to know is, why were the cancer rates higher the further they went south??


In Figure 4 they added more countries and the internal cancer rate vs latitude graph turned into a scatter plot. So sun exposure can't explain it.

Looking at Figure 2 again, which is the basis for the claim of higher internal cancer incidence in the sunnier countries, as someone in the physical sciences I would be too ashamed to draw most of those lines.


In the study they say:

However, taking more countries into consideration, we see that no reliable north–south gradient can be extracted (Fig. 4). There is a large variation of the incidence rates by factors of Posted Image50 and 5 for prostate cancer and breast cancer, respectively. Even for countries at the same latitude, large differences are found. From this epidemiological variation, we can conclude that genetical, dietary, and environmental factors, other than sun exposure, play major roles and may completely mask the effects of vitamin D.

If you look at the graph though, there is definitely a correlation between the 2 even though there is a fair ammount of noise. Simply compare the upper latitude quartile top the lower latitude quartile: It looks like an almost 2x difference in average incedence rates.


Posted Image
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#16 krillin Re: Take or avoid vitamin D supplements?

  • Location:USA

Posted 15 January 2008 - 09:06 PM

If you look at the graph though, there is definitely a correlation between the 2 even though there is a fair ammount of noise. Simply compare the upper latitude quartile top the lower latitude quartile: It looks like an almost 2x difference in average incedence rates.
Posted Image


Yeah, but their first line sloped down, with sun increasing cancer incidence. The line you want to draw makes sun decrease cancer incidence. It's probably confounded by the diseases of civilization effect, since most sunny countries are poor and don't have as much meat eating or obesity.
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#17 niner Re: Take or avoid vitamin D supplements?

  • Location:Philadelphia

Posted 16 January 2008 - 03:21 AM

If you look at the graph though, there is definitely a correlation between the 2 even though there is a fair ammount of noise. Simply compare the upper latitude quartile top the lower latitude quartile: It looks like an almost 2x difference in average incedence rates.
Posted Image


Yeah, but their first line sloped down, with sun increasing cancer incidence. The line you want to draw makes sun decrease cancer incidence. It's probably confounded by the diseases of civilization effect, since most sunny countries are poor and don't have as much meat eating or obesity.

I agree with you regarding the diseases of civilization effect, and then there's "Southern Cooking", if you're dealing strictly with the US.. But in these charts, it looks to me that aside from a lot of noise, the data does go in the right direction. As latitude increases, (going away from the equator) you do see a trend toward increasing incidence, assuming I'm reading the y-axis properly.
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#18 edward Re: Take or avoid vitamin D supplements?

  • Location:Southeast USA

Posted 16 January 2008 - 03:23 AM

Take or avoid vitamin D supplements


Umm... Take


Edit: At much higher doses than the RDA, everything I have read points to doses over 2000 IU. Sorry to be blunt, a nice discourse is always good

Edited by edward, 16 January 2008 - 03:28 AM.

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#19 krillin Re: Take or avoid vitamin D supplements?

  • Location:USA

Posted 16 January 2008 - 05:11 AM

I agree with you regarding the diseases of civilization effect, and then there's "Southern Cooking", if you're dealing strictly with the US.. But in these charts, it looks to me that aside from a lot of noise, the data does go in the right direction. As latitude increases, (going away from the equator) you do see a trend toward increasing incidence, assuming I'm reading the y-axis properly.


You're reading it correctly and I hope you're right. But one would expect to be able to reach better conclusions from a graph like Figure 2 where standard of living has been (kind of sort of) controlled for, and there's no way to draw an uphill line through that data.
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#20 lucid Re: Take or avoid vitamin D supplements?

  • Location:Austin, Tx

Posted 16 January 2008 - 05:32 PM

I agree with you regarding the diseases of civilization effect, and then there's "Southern Cooking", if you're dealing strictly with the US.. But in these charts, it looks to me that aside from a lot of noise, the data does go in the right direction. As latitude increases, (going away from the equator) you do see a trend toward increasing incidence, assuming I'm reading the y-axis properly.


You're reading it correctly and I hope you're right. But one would expect to be able to reach better conclusions from a graph like Figure 2 where standard of living has been (kind of sort of) controlled for, and there's no way to draw an uphill line through that data.

Controlling for stanard of livng is not what we would really want to control for: What we really want to control for is 'non-sun-exposure related' cancer incedences which is dependent largely upon diet and then a whole slew of other things. So comparing regions with a similiar diet may be more helpful, but even then if one culture has a similiar diet but uses a few different spices (lots of spices are strongly anti-inflamitory) then that could skew results. All that to say, that since it looks too difficult to control for 'non-sun-exposure related' cancer incedences: figure 4 is going to be the most valuable.

I just find mountains and mountains of studies corroberating low latitude and Vit D to decreased cancer incedences.
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#21 amyproal Re: Take or avoid vitamin D supplements?

Posted 17 January 2008 - 07:35 PM

Hi! This is Amy Proal. I wrote the article referenced at the start of the thread about vitamin D.

Dr. Marshall is not concerned with vitamin D toxicity. Rather his molecular modeling research has clarified the actions of the two vitamin D metabolites 25-D and 1,25-D. The Vitamin D Receptor (VDR) is a fundamental receptor of the body – it controls the expression thousands of genes, as well as the activity of the innate immune system and the antimicrobial peptides. If you think of the VDR as a switch, 25-D (which is a corticosteroid) turns it off (inactivates it) and 1,25-D turn it on (activates it). What is commonly believed among vitamin D researchers is that if people supplement with extra vitamin D it will be converted into 1,25-D and activate the VDR. Unfortunately, Marshall's work revealed that the type of vitamin D derived from supplements and sun remains, for the most part, in it's precursor form 25-D. This means that the extra vitamin D we get from fortified food products and supplements is turning the VDR off, not on. That causes a decrease in immune function and gene transcription.

Yet we always hear studies saying that vitamin D is beneficial. What is actually going on is that most diseases of "unknown cause" are actually caused by mutated bacterial forms called L-form bacteria. You can read more about them on my website www.bacteriality.com. The immune system secretes inflammatory molecules in response to the presence of these bacteria. When patients take extra vitamin D, it remains as 25-D, the corticosteroid that temporarily lowers the patient's inflammation. This may seem like good thing but the problem is that because the immune system is being suppressed, L-form bacteria and other pathogens can spread with much greater ease, making people much sicker in the long run.

In the same vein, we are often told that vitamin D deficiency is a risk factor for chronic disease. Again, misunderstanding reigns supreme – namely mainstream medicine fails to realize that the low levels of 25-D seen in patients with chronic disease are not CAUSING the disease, but are simply a RESULT of the disease process. As patients accumulate L-form bacteria, the level of the active vitamin D metabolite 1,25-D rises as a result of bacteria-induced blockage of the VDR. As described by Marshall in his newly published paper "Vitamin D discovery outpaces FDA decision making," blockage of the VDR affects numerous feedback pathways – resulting in a downregulation of the body's level of 25-D. This means that what is commonly interpreted as a deficiency is nothing more than a marker of L-form infection.

Speaking of Dr. Marshall's newly published paper, here's a link to the preprint. It will be published in the February 1st issue of BioEssays which is a well-known peer reviewed journal.

http://TrevorMarshal...ll-Preprint.pdf

Dr. Marshall will also be chairing an entire session "The Vitamin D Receptor, Vitamin D, and Immune Disease." at the upcoming International Conference on Autoimmunity. As you can see his views are being increasingly considered by the mainstram mediciine and he is certainly onto something. I know what he has put forth is controversial, but something about the current view is clearly wrong. As we continue to take more vitamin D supplements and fortify more products the rate of chronic disease is only going up.

One last thing. Dr. Marshall is not leading a cult! True, maybe a handful of people have been banned from the Marshall Protocol study site, but that is not a common occurrence. The thing is, the moderators of the board make it clear that the study site is not a support board or really a discussion board. It is a board where you come to post progress when your are on the Marshall Protocol. All questions should pertain to the treatment and how to best follow the guidelines. If you have problems with the Marshall Protocol then the study site is not the place to post them. You can bring them up elsewhere. But the site has one mission only – to help people who want to do the Marshall Protocol proceed with treatment as effectively as possible.

Best,

Amy

PS As for cancer rates being lower near the equator. Consider this. Generally, people living around the equator are members of third world countries. If they fall ill with cancer what are they going to do? Call the nearest radiologist and oncologist? Unfortunately, they have little access to healthcare and most of their cases go undocumented. The opposite is true for people in the northern hemisphere, where most first world countries are located. These people have the money and education to pay a multitude of doctors for cancer therapy, meaning that their cases are documented and accounted for. The same type of bias impacted CFS. For a long time, CFS was called the "yuppie flu." Supposedly it was a disease that affected wealthy, white people. Then, it turned out that wealthy white people were the only ones who could afford enough doctor visits to get diagnosed with CFS. It is now accepted that the disease affects all members of the population equally. Not to mention the fact that people living near the equator have dark skin. Dark skin produces vitamin D at a much slower rate than white skin. Plus, there is much evidence pointing to the fact that cancer is a bacterial disease. It's common knowledge that pathogens are able to infect the host with greater ease in cold weather. Clearly more people catch the flu during the winter rather than the summer.

PPS. Since this is a board about aging I wonder if any of you would be interested in my article "Aging and the resurrection of the immune system"

http://bacteriality....07/11/18/aging/

I'd be interested in feedback....

Edited by amyproal, 17 January 2008 - 07:45 PM.

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#22 nameless Re: Take or avoid vitamin D supplements?

Posted 17 January 2008 - 08:35 PM

Hi! This is Amy Proal. I wrote the article referenced at the start of the thread about vitamin D.

In the same vein, we are often told that vitamin D deficiency is a risk factor for chronic disease. Again, misunderstanding reigns supreme – namely mainstream medicine fails to realize that the low levels of 25-D seen in patients with chronic disease are not CAUSING the disease, but are simply a RESULT of the disease process. As patients accumulate L-form bacteria, the level of the active vitamin D metabolite 1,25-D rises as a result of bacteria-induced blockage of the VDR. As described by Marshall in his newly published paper "Vitamin D discovery outpaces FDA decision making," blockage of the VDR affects numerous feedback pathways – resulting in a downregulation of the body's level of 25-D. This means that what is commonly interpreted as a deficiency is nothing more than a marker of L-form infection.


I admit I am not aware of Dr. Marshall's theories, but if what he says is true, would this indicate vitamin D supplementation is not warranted ONLY when 1, 25-D is high, since according to the theory stated, L-form bacteria should raise 1, 25-D? Is the danger with vitamin D supplementation only for people with chronic illness caused by L-form bacteria, or does he suggest nobody at all supplement with vitamin D, ever?

If L-form bacteria causes low levels of 25-D, and causes a rise in 1, 25-D (such as in sarcoidisis people), I can see this making some sense (assuming any of the theory is true). However, for others (which is probably most people), if their 1, 25-D is low-normal, and 25-D is low, why would vitamin D supplementation be a bad thing?

I supplement with vitamin D, as I had a low 25-D level. However, my 1, 25-D was normal and remains normal even after correcting my deficiency.
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#23 lucid Re: Take or avoid vitamin D supplements?

  • Location:Austin, Tx

Posted 17 January 2008 - 08:42 PM

It is worth mentioning that lots of the vitamin D fortification which Dr. Marshal talks about is food being fortified with vitamin D2 (formed by irradiating a plant sterol) while D3 is produced in the human skin where it then goes to be synthesized in the liver to form 25-hydroxyvitamin D3 and then to the kidney to form 1,25-dihydroxyvitamin D3.

I skimmed the paper you posted of Dr. Marshall's and depth read about half of it. I didn't see any references to studies of whether Vitamin D3 when supplemented increases 1,25-dihydroxyvitamin D3. Doing some sniffing around, it appears that it does as would be expected:
http://www.jbc.org/c...act/249/23/7584

Regulation of 25-Hydroxyvitamin D3-1-hydroxylase in Vivo
Helen L. Henry 1, Ronald J. Midgett 1, and Anthony W. Norman 1

From the 1 From the Department of Biochemistry, University of California, Riverside, California 92502

The elucidation of the factors which govern the production by the kidney of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) is essential to an understanding of calcium homeostasis. Changes in the specific activity of the renal 25-OH-cholecalciferol-1-hydroxylase (1-hydroxylase) were followed after alterations in dietary vitamin D, calcium, and phosphorus or parathyroidectomy using an enzyme assay which measures initial reaction rates. 1-Hydroxylase specific activity varied over a 5- to 20-fold range with changes in dietary vitamin D; it was decreased to a specific activity of 0.1 to 0.6 pmole per min per mg of protein by administration of vitamin D3 (1.6 nmoles per day) or equally effectively by administration of 1,25-dihydroxyvitamin D3 (0.52 nmole per day), and it increased markedly to a level of 0.7 to 1.8 pmoles per min per mg of protein upon withdrawal of the steroids. These changes were not dependent upon measurable changes in serum calcium and occurred regardless of dietary calcium and phosphorous levels. The time period required for the enzyme activity to fall to values characteristic of a vitamin D-repleted chick was inversely proportional to the magnitude of the dose of vitamin D3 given (7 days with 3.2 nmoles per day; 2 days with 32.5 nmoles per day).

In the continued presence of vitamin D3, the 1-hydroxylase activity is modulated over a more narrow range (0.1 to 0.6 pmole per min per mg of protein) and enzyme levels reflect the dietary availability of calcium. Changes in dietary calcium were reflected by parallel changes in serum calcium. There was a highly significant (p < 0.001) inverse correlation between 1-hydroxylase activity and serum Ca2+ levels. No significant correlations were found between the enzyme activity and serum phosphorous or renal inorganic phosphorous levels.

Parathyroidectomy of cholecalciferol-depleted chicks resulted in a decrease, in 24 hours, of 1-hydroxylase activity to levels characteristic of vitamin D-treated chicks (0.2 to 0.04 pmoles per min per mg of protein). This suggests that parathyroid hormone status is equally as important as calciferol status in determining 1-hydroxylase specific activity. The half-life and rates of synthesis and degradation of 1-hydroxylase in cholecalciferol-deficient and -repleted chicks were determined by measuring enzyme activity following cycloheximide treatment (Berlin, C. M., and Schimke, R. T. (1965) Mol. Pharmacol. 1, 149). Vitamin D status had no effect on the half-life or degradation rate (t1/2 = 4 to 5 hours); the rate of synthesis in deficient birds is 4.7 times that in vitamin D-repleted birds.

In summary, the two major components which regulate the steady state level of 25-OH-D3-1-hydroxylase (vitamin D status and serum calcium-parathyroid hormone) appear to exert their effect by changes in the rate of the biosynthesis of this enzyme.
Submitted on April 12, 1974


Edited by lucid, 17 January 2008 - 08:43 PM.

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#24 krillin Re: Take or avoid vitamin D supplements?

  • Location:USA

Posted 17 January 2008 - 09:18 PM

Dr. Marshall is not concerned with vitamin D toxicity. Rather his molecular modeling research has clarified the actions of the two vitamin D metabolites 25-D and 1,25-D. The Vitamin D Receptor (VDR) is a fundamental receptor of the body – it controls the expression thousands of genes, as well as the activity of the innate immune system and the antimicrobial peptides. If you think of the VDR as a switch, 25-D (which is a corticosteroid) turns it off (inactivates it) and 1,25-D turn it on (activates it).


First allow me to apologize for being so harsh to you earlier. I didn't know you were so young and sick.

I think you mean secosteroid, not corticosteroid. I have yet to see any in-vivo or in-vitro evidence that 25-D is a VDR antagonist. The first study below found that 25-D cannot displace 1,25-D from the VDR. The second study found that 25-D is 1% as effective as 1,25-D. And since there is so much more 25-D than 1,25-D, 25-D accounts for 1/8 of total vitamin D effect.

Am Rev Respir Dis. 1991 Jun;143(6):1376-80.
Expression of 1,25(OH)2D3 receptors on alveolar lymphocytes from patients with pulmonary granulomatous diseases.
Biyoudi-Vouenze R, Cadranel J, Valeyre D, Milleron B, Hance AJ, Soler P.
INSERM U.82, Faculté de Médecine Xavier Bichat, Departement de Pneumologie, Hôpital Tenon, Paris, France.

1,25(OH)2D3 is known to be produced at sites of granulomatous reactions. In order to characterize the cell types that are targets for this immunoregulatory hormone, we have evaluated the expression of 1,25(OH)2D3 receptors on peripheral blood T-lymphocytes and those recovered from the lung by bronchoalveolar lavage from patients with pulmonary granulomatous diseases (tuberculosis and sarcoidosis) and from normal control subjects using combined autoradiographic and immunohistochemical techniques. 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 (receptor-positive lymphocytes: sarcoidosis, 20 +/- 12%; tuberculosis, 31 +/- 17%). In contrast, blood lymphocytes from patients with granulomatous diseases did not express detectable 1,25(OH)2D3 receptors. The percentage of lavage T-lymphocytes expressing 1,25(OH)2D3 receptors was significantly greater for patients with tuberculosis presenting with isolated hilar adenopathy than for patients with pulmonary infiltrates and/or cavities. 1,25(OH)2D3 receptors were expressed to a greater extent on CD8+ T-lymphocytes than on CD4+ T-lymphocytes in sarcoidosis, whereas a greater proportion of CD4+ than of CD8+ T-lymphocytes from patients with tuberculosis were receptor-positive. These findings support the conclusion that the interaction of 1,25(OH)2D3 with its receptor on T-lymphocytes may play an important role in the regulation of granulomatous reactions, but because these receptors are expressed on different lymphocyte populations, the net effect of this potent immunoregulatory molecule is likely different in sarcoidosis and tuberculosis.

PMID: 1646583

J Clin Endocrinol Metab. 1997 Dec;82(12):4111-6.
Calcium absorptive effects of vitamin D and its major metabolites.
Heaney RP, Barger-Lux MJ, Dowell MS, Chen TC, Holick MF.
Creighton University, Omaha, Nebraska 68131, USA.

The absorptive response to graded doses of vitamin D3, 25(OH)D, and 1,25(OH)2D was measured in healthy adult men after treatment periods of eight, four, and two weeks, respectively. While no relationship was found between baseline absorption and serum vitamin D metabolite levels, all three vitamin D compounds significantly elevated 45Ca absorption from a 300 mg calcium load given as part of a standard test meal. 1,25(OH)2D was active even at the lowest dose (0.5 microgram/day), and the slope was such that doubling of absorption would occur at an oral dose of approximately 3 micrograms/day. 25(OH)D was also active in elevating absorption and did so without raising total 1,25(OH)2D levels. On the basis of the dose response curves for 1,25(OH)2D and 25(OH)D, the two compounds exhibited a molar ratio for physiological potency of approximately 100:1. The absorptive effect of vitamin D3 was seen only at the highest dose level (1250 micrograms, or 50,000 IU/day) and was apparently mediated by conversion to 25(OH)D. Analysis of the pooled 25(OH)D data from both the 25(OH)D- and vitamin D3-treated groups suggests that approximately one eighth of circulating vitamin D-like absorptive activity under untreated conditions in winter may reside in 25(OH)D. This is a substantially larger share than has been predicted from studies of in vitro receptor binding.

PMID: 9398723

As we continue to take more vitamin D supplements and fortify more products the rate of chronic disease is only going up.

Most people take the inadequate RDA as the less-effective D2 form in an ineffective tablet/powder form. Only the hardcore informed people are taking 1000 IU or more of D3 softgels.

As for cancer rates being lower near the equator. Consider this. Generally, people living around the equator are members of third world countries. If they fall ill with cancer what are they going to do? Call the nearest radiologist and oncologist? Unfortunately, they have little access to healthcare and most of their cases go undocumented.


Early detection and treatment would be problematical, but it's pretty easy to spot cancer in someone dead or nearly dead. They have to put something on the death certificate.
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#25 amyproal Re: Take or avoid vitamin D supplements?

Posted 18 January 2008 - 03:09 PM

Good morning,

All of you pose excellent questions. I think I can answer some of them.

One thing Marhshall's work emphacizes is the fact that the body's regulation of the vitamin D metabolites is extremely complex, but it appears that the body works quite well on it's own to keep 25-D and 1,25-D in a healthy range if left alone. The second part of his paper shows all the intricate feedback pathways that regulate levels of the two metabolites. Supplementation interferes with this normal homeostasis which is a big problem.

As Marshall has said, "Vitamin D is a steroid hormone, and the body regulates the production of all it needs."

What he is mainly arguing against is the use of oral supplements in the form of D2 which, if the person is truly deficient may be converted to 1,25-D, but if the person is not (and most Amercians arn't) it remains as 25-D which starts to block the VDR rather then activate it. You are absolutely right - I meant to say that 25-D is secosteroid not a corticosteroid, sorry! Then, if the VDR is blocked, the innate immune system, the trascription of thousands of genes, and the production of the AMPs are all twarted. This goes a long way towards explaining why the rate of illness among our population continues to rise.

D3 from sunlight can be converted from 25-D to 1,25-D in the liver. But in my understanding, I think that if a person gets too much sunlight some can remain as 25-D. The other thing is that at high levels 1,25-D becomes immunosuppressive. As you can tell this is all very complex, which is why I encourage you to read all of Dr. Marshall's paper. So excessive sun exposure is going to raise 1,25-D to a level where it also slows the immune system.

Yes, There is a difference between the amount of vitamin D one would consume if they were sick or healthy. Healthy people should aim to keep thier level of 25-D under about 20 ng/ml which is the point at which it will begin to block the VDR. The problem is that this level is considered "deficient" by American doctors. Since we have added vitamin D to the food chain the level of 25-D considered to be "healthy" has been inflated. But studies of people in cultures that do not fortify with D show that their levels of 25-D are indeed under 20 ng/ml, even the eskimos who eat alot of fatty fish. What seems to be the case is that if a person eats only non-fortified foods and does not seek the sun, their vitamin D levels will stay in a range that won't affect immune function.

People who are infected with L-form bacteria generally show high levels of 1,25-D because extra 1,25-D is released by the immune system in response to their presence. 1,25-D also functions as a cytokine, so this increases inflammation and thus symptoms. So patients who have L-form bacteria are encouraged to use the Marshall Protocol. In this case, they want to avoid as much vitamin D as possible in order to keep 25-D very low (make sure there is no VDR blockage) and also keep 1,25-D low. Then the ARB mediation Benicar, which is a potent VDR agonist, is used to activate the VDR. As the patient proceeds through treatment 1,25-D begins to stabilize and activates the VDR along with Benicar, further enhancing immune function. Pulsed, low dose antibiotics are introduced and because the immune system is in good shape it can kill the L-forms weakened by the antibiotics.

But anyone who is ill would want to keep 25-D low in order to ensure the VDR is not blocked and 1,25-D does not become too high, thus exascerbating inflammation.

In essence as Dr. Marshall has stated, "We need to discard the notion that vitamin D affects a disease state in a simple way. Vitamin D affects the expression of over 1,000 genes, so we should not expect a simplistic cause and effect between vitamin D supplementation and disease. The comprehensive studies are just not showing that supplementary vitamin D makes people healthier."

Hope this helps!

Amy

Edited by amyproal, 18 January 2008 - 03:12 PM.

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#26 lucid Re: Take or avoid vitamin D supplements?

  • Location:Austin, Tx

Posted 18 January 2008 - 03:51 PM

Hey Amy,
Thank you for your interesting posts. Could you perhaps post a study to show 25-D acting to block 1,25-D? As krillin pointed out:

I have yet to see any in-vivo or in-vitro evidence that 25-D is a VDR antagonist. The first study below found that 25-D cannot displace 1,25-D from the VDR. The second study found that 25-D is 1% as effective as 1,25-D. And since there is so much more 25-D than 1,25-D, 25-D accounts for 1/8 of total vitamin D effect.


I will also have to disagree with the assumption of Dr. Marshall's that: "Vitamin D is a steroid hormone, and the body regulates the production of all it needs."
For 2 principle reasons:

#1: There are plenty of hormones which our body stops regulating properly as we age. Furthermore, how those hormones are regulated can be heavily effected by diet and exercise. The point here being that poor life habits can ultimately effect your body's regulation of these hormones: Hence it is not necessarily a good assumption that because your body will optimally regulate a particle hormone.

#2: Where as our lifestyle and diet are so drastically different from our ancestors, it is not fair to assume that our bodies will properly regulate our hormones when we live indoors, eat much different foods and are much more sedentary than the creatures that we were for much of the past 200,000 years of evolution. If you spend lots of time outdoors like our long gone ancestors supplementation of d3 may not be as prudent of a choice.

Edited by lucid, 18 January 2008 - 03:55 PM.

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#27 amyproal Re: Take or avoid vitamin D supplements?

Posted 19 January 2008 - 03:19 AM

Hi Lucid,

The issue at stake here is not whether 25-D can displace 1,25-D from the 1,25(OH)2D3 receptor, which is discussed in the first study posted by Krillen. The issue is how each of the vitamin D metabolites binds the Vitamin D Receptor. The second study posted by Krillin discusses the absorptive response to graded doses of vitamin D3, 25(OH)D, and 1,25(OH)2D, and absorption has nothing to do with their affinities for the VDR.

Molecular data (shown in the presentation below) shows that the affinity of 25-D for the VDR is 0.07. The affinity of 1,25-D for the VDR is 0.03. So they both have quite high affinities for the receptor and both can bind it with ease.

It is Marshall’s molecular models which show that 25-D is a VDR antagonist. Take a look at the following presentation that he gave at the 2006 AAEM conference.

Marshall TG: Molecular Mechanisms Driving the Current Epidemic of Chronic Disease. Seminar presentation, Bio21, University of Melbourne, Australia, 16 Nov 2006
Online Video available from URL: http://autoimmunityr...h.org/bio21.ram
Transcript available from URL http://autoimmunityr..._bio21_2006.pdf

Towards the middle of the presentation you will see the models Marshall’s used to determine how 24, 25-D, 25, and 26-D, and 1,25-D lie in the VDR binding pocket. All of these forms of vitamin D have one alpha hydroxylation at helix 12 which is known to be essential to binding to the promoters which allow the VDR to become active. In contrast, 25-D lacks this hydroxylation meaning it is unable to activate the receptor.

Then Marshall goes on the show just how similar a molecule of 25-D is to a molecule of prednisone (a corticosteroid). It’s got the five member ring and six member ring with methane that’s characteristic of all sterols. The only difference between the two molecules is one carbon bond that has been cleaved by an electrocytic reaction. Interestingly, that actually gives 25-D a higher affinity for some of the nuclear receptors because there are more degrees of freedom for the bottom ring due to the fact that is has two double bonds rather than one.

As for hormone regulation not occurring properly as we age, does that justify adding vitamin D to milk, yogurt, cheese, orange juice, pastas, cereals etc. for the entire population from infants through adults? If I told you we should add prednisone to the food supply you would tell me I’m crazy. So why are we adding vitamin D? Rickets occurs in a small subset of the population and supplementation should be carefully tailored to that group of people only.

Consider this – why do many hormone pathways go off balance as we age? Is it because all of the population begins to acquire L-form bacteria to some degree? Then, due to increased inflammation 1,25-D levels begin to rise. 1,25-D, which is sometimes referred to as the body’s master hormone, controls feedback of all the body’s other hormones – stress, sex, etc. So perhaps by killing the L-form bacteria at the heart of so many diseases including “healthy aging” which is due largely the result of infection as well would cause hormonal pathways not go awry.

Proper levels of the vitamin D metabolites are so essential that the body can manufacture them in numerous ways. For example, the conversion of 7-dehydrocholesterol to pre-vitamin D is also observed in macrophages and intestinal cell lines, so even if a person wasn’t eating D or in the sun they could still make vitamin D.

If you can’t accept molecular data, then get on the Marshall Protocol study site and read the progress of the thousands of patients who are recovering only after removing vitamin D from their diets. As patients on the Marshall Protocol kill bacteria, they get a “herxheimer” response, or a rise in symptoms due to the release of bacterial endotoxins. Many patients do not respond in this manner to the antibiotics used by the treatment unless their 25-D levels have dropped below 20 ng/ml. So the molecular data has been upheld by clinical data as well.

Best,

Amy
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#28 lucid Re: Take or avoid vitamin D supplements?

  • Location:Austin, Tx

Posted 19 January 2008 - 04:13 AM

Not much time atm. But I can't seem to watch the lecture, possibly becuase I am using Real Alternative instead of the original Real Player Anyone else having the problem?

I haven't had time to read through all of his lecture via the pdf, but a quick question: It seems that if you take 25-D directly via D2 commonly found in foods then you by-pass the calcium down-regulation mechanism? In this sense if you supplement D3 then you are still having your 1,25-D levels regulated properly since VDR activation is going to control the ammount of D3 getting converted into 25-D?

I like Dr. Marshall's work. Maybe he would be interested in doing one of the sunday night chats here at some point? People would need to get more familiar with his lectures to have some questions to ask.

More later.

Edited by lucid, 19 January 2008 - 04:13 AM.

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#29 krillin Re: Take or avoid vitamin D supplements?

  • Location:USA

Posted 19 January 2008 - 04:47 AM

The issue at stake here is not whether 25-D can displace 1,25-D from the 1,25(OH)2D3 receptor, which is discussed in the first study posted by Krillen. The issue is how each of the vitamin D metabolites binds the Vitamin D Receptor. The second study posted by Krillin discusses the absorptive response to graded doses of vitamin D3, 25(OH)D, and 1,25(OH)2D, and absorption has nothing to do with their affinities for the VDR.

Molecular data (shown in the presentation below) shows that the affinity of 25-D for the VDR is 0.07. The affinity of 1,25-D for the VDR is 0.03. So they both have quite high affinities for the receptor and both can bind it with ease.


If 25-D really had higher affinity for the receptor, wouldn't it be able to displace 1,25-D? I don't trust computer models. I've seen too many of them give horrible predictions, sometimes even in the wrong direction. One of my crusty old profs told us that "Theory guides. Experiment decides."

Anyway, relative affinities don't really matter here, since 25-D and 1,25-D are both VDR agonists. Active calcium absorption requires the VDR, and both 25-D and 1,25-D allow active calcium absorption.

If you can’t accept molecular data, then get on the Marshall Protocol study site and read the progress of the thousands of patients who are recovering only after removing vitamin D from their diets. As patients on the Marshall Protocol kill bacteria, they get a “herxheimer” response, or a rise in symptoms due to the release of bacterial endotoxins. Many patients do not respond in this manner to the antibiotics used by the treatment unless their 25-D levels have dropped below 20 ng/ml. So the molecular data has been upheld by clinical data as well.


That could be explained solely by a decrease in the excessive 1,25-D causing immune suppression. We need more evidence to conclude that 25-D is immunosuppressive.
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#30 krillin Re: Take or avoid vitamin D supplements?

  • Location:USA

Posted 19 January 2008 - 05:04 AM

Not much time atm. But I can't seem to watch the lecture, possibly becuase I am using Real Alternative instead of the original Real Player Anyone else having the problem?

I haven't had time to read through all of his lecture via the pdf, but a quick question: It seems that if you take 25-D directly via D2 commonly found in foods then you by-pass the calcium down-regulation mechanism? In this sense if you supplement D3 then you are still having your 1,25-D levels regulated properly since VDR activation is going to control the ammount of D3 getting converted into 25-D?

I like Dr. Marshall's work. Maybe he would be interested in doing one of the sunday night chats here at some point? People would need to get more familiar with his lectures to have some questions to ask.

More later.


I'm not sure what you're getting at here. No one sells 25-D. Everything is D (Except Perque sells some things with 1,25-D, but I wouldn't recommend them. The therapeutic and toxic doses are too close.), which gets converted to 25-D in the liver. Conversion to 1,25-D is feedback controlled (gets higher with lower dietary calcium) unless you have macrophages going crazy. In that case you can justify purging D from your diet until you kill all the bacteria. But healthy people benefit from 25-D above 36-40 ng/ml. Figure 6 from my first post makes the case rather convincingly.
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