How Vitamin D Reduces the Incidence of Cancer

Dr. Cedric Garland discusses the DINOMIT model of how vitamin D reduces the incidence of cancer.

How Vitamin D Reduces the Incidence of Cancer: The DINOMIT Model

In a new study, researchers at the UCSD School of Medicine and Moores Cancer Center used a complex computer prediction model to determine that intake of vitamin D3 and calcium would prevent 58,000 new cases of breast cancer and 49,000 new cases of colorectal cancer annually in the US and Canada. The researchers' model also predicted that 75% of deaths from these cancers could be prevented with adequate intake of vitamin D3 and calcium. Join Dr. Cedric Garland, lead researcher on the study, as he discusses the implications of these findings and the proposed actions.

Hidden Risks and Dangers of the Marshall Protocol

An individual made the following post on a Fibro. bulletin board last month, which I found well constructed and inclusive of several citations. This individual was on the MP for a few years and did not have a favorable experience with regards to their Chronic Fatigue Syndrome (CFS). Sadly, this doesn't appear to be an isolated case, and many additional veterans of the protocol are reporting similar unfavorable results by engaging in a protocol designed to restore health that includes radically disobeying the laws of mother nature.

“The human body does not require sunlight, nor foods containing Vitamin D, in order for it to function correctly. The human body can manufacture all the Vitamin D it needs from its own 7-dehydrocholesterol. Clinical medicine is just plain wrong on its understanding of the actions of Vitamin D.” Trevor Marshall (1)

The Marshall Protocol (MP) claims to cure CFS and FM, as as such, is a very polarizing topic. People are either really for it, or really against it. Seduced by the molecular modeling and hope of a cure, I was on the protocol for almost two years. However, after almost landing in ER and experiencing a permanent deterioration in all my CFS symptoms, I have learnt first-hand of the dangers and risks of the MP, none of which I was warned. The MP worsened my existing CFS symptoms such as fatigue, sleep dysfunction, muscle and joint pain and created new symptoms such as neuropathy, parenthesisa, breathing difficulties, cardiac pain and tinnitus which have persisted. Thus I feel that it is my duty to warn others who may be considering the MP, which continues to attract many new patients, of all the hidden risks so that they can make a fully informed decision about whether to undertake this protocol.

To read more, the entire post can be found here: Hidden Risks and Dangers of the Marshall Protocol

The MP > Does Exogenous Vitamin D Really Dock & Deactivate the VDR and Innate Immunity?

Since first discovering the low carb forum I became very interested in vitamin D and became convinced that supplementation was necessary to maintain good health due to the geographic location I reside in (north mid-west U.S.) and the unnatural amount of sunlight I get exposed to on average. Over time I became aware of what is known as the Marshall Protocol (aka the 'MP') and immediately absorbed all of the various information surrounding the protocol and the originator and camp's theories regarding vitamin D and the connection with chronic disease.

In short, one of their main theories is that 'exogenous' (taken in from foods and supplements as opposed to created internally from sun and/or bright light exposure) vitamin D (25OHD, the storage form) is immunsuppressive because it actively binds to, displaces, and deactivates the active form of vitamin D (calcitriol, 1,25OHD3) from the vitamin D (nuclear) receptor (VDR).

These claims by Marshall and the MP camps are only substantiated (to my knowledge) by 'molecular modeling computer simulations' otherwise known as in-silico experiments. There is much controversy around Marshall's theories and people tend to be on polar opposites when concluding whether the theories are valid or not. The in-silico experiments are difficult for many to swallow to adequately justify his theory that 25OHD binds and deactivates the VDR, because they are essentially in-vitro experiments that do not account for many variables that exist when 25OHD exists in a living organism such as a human being.

Being someone who benefits from vitamin D supplementation and believing it to be a vital nutrient for human health and well being, especially when consumed or obtained in synergy with the other fat soluble nutrients like vitamin A and vitamin K2 (Price's once elusive 'X-factor' activator) and especially after reading Weston Price's Nutrition and Physical Degeneration, I began searching for scientific explanations that would dispel Marshall's theory that 25OHD vitamin D shuts down innate immunity in a dose dependent manner and has the ability to directly bind to and deactivate the VDR.

Posted by Josiah Zayner

http://tinyurl.com/ae7hxz

Myself being a molecular biologist and competent in the use of molecular dynamics simulations it is apparent that Mr. Marshall's work is incorrect and he consistently refuses to provide any parameters used in his simulations. See comments on:

http://precedings.nature.com/documents/52/version/1
http://precedings.nature.com/documents/164/version/1

---

Originally Posted by Anonymous M.D.

http://tinyurl.com/ae7hxz

I'm an M.D. whose attention was drawn to Trevor Marshall recently. Going to his website, he appears to be an intelligent, somewhat charismatic person who has sold some interesting ideas to a bunch of chronic disease sufferers and in the process has created the usual cult of hopeful pseudoscientists who are drawn to such efforts. There are a few interesting ideas presented there, and in fairness I suspect he may even be onto a few things with respect to sarcoidosis and maybe one or two other conditions that actually are exacerbated by high levels of D/calcium. Otherwise, it's apparent that there's a lot of sloppiness, speculation, and spin, and frankly I find many of their claims with respect to Vitamin D's harmfulness to be not only unsubstantiated but downright scary and having the potential to do great harm--particularly since he/they have a paucity of evidence for their positions and seem to disdain a great many actual clinical research studies that contradict their thesis that Vitamin D supplementation is generally bad. (A greater value is apparently placed on his 'in silico experiments'. That smacks of just a wee bit of hubris in my book.)

His topics are deep (seeing as how they deal with biochemistry and molecular biology on a level that's too complex to be properly followed by any who aren't versed in those subjects), but despite the richness of detail of his arguments there are some important errors. For any of his followers who happen to be reading this, one such example would be talking about binding constants and the measured competitive antagonism of calcidiol (aka 25-OHD) on the VDR. Such antagonism may be measurable in vitro, but in vivo it's actually irrelevant. As Marshall's followers all well know, VDRs are NUCLEAR receptors, and as such they aren't directly exposed to circulating (plasma) calcidiol. In the plasma, calcidiol is bound to DBP (D binding protein) and (to a much lesser extent) albumin. Following transport through the plasma, DBP and calcidiol in turn bind to megalin proteins that are expressed on some cell surfaces, which binding in turn triggers clathrin to induce endocytosis. Following endocytosis, calcidiol is released from DBP into the cytoplasm, where it is immediately bound to hsc70 (a constitutively expressed chaperone protein that binds many things, including other D-metabolites such as calcitriol). From there, different metabolites of D appear to be selectively directed to specific intracellular organelles. Most relevantly, hsc70-bound calcitriol (aka 1,25(OH)2D, aka the "active D metabolite") has a higher binding affinity to a nuclear chaperone called BAG-1 than hsc70-bound calcidiol does (see http://jme.endocrinology-journals.o...e2=tf_ipsecsha). This is important because since BAG-1 guides D-metabolites to the VDR, it means that high calcidiol levels won't significantly interfere with VDR binding of calcitriol--and thus Marshall's "in silico"-supported hypothesis that exogenous Vitamin D supplementation interferes with VDR activation turns out to be erroneous. (For his fans, I also don't know what the significance of this VDR-presenting mechanism might be with regard to Marshall's proposed use of Benicar as an artificial VDR agonist. It might or might not be relevant.)

Anyway, history may yet vindicate some of Marshall's other ideas and prove me wrong about him, but for now I see every indication that this guy is well-meaning but dangerously overconfident about the veracity of his theories. If I'm right, then unless/until such theories are thoroughly discredited he will remain an intelligent and articulate person who can convince a lot of other people to join him in his misguided crusade to get the "truth" out about the dangers of Vitamin D. For his fellow co-sufferers of sarcoidosis (and possibly those few other rare conditions exacerbated by high calcium levels) this might be forgivable. For the other 99+% of us, such efforts may have potentially grave consequences. If the thrust of the emerging body of peer-reviewed Vitamin D research is to be believed, a billion people on this planet currently suffer from Vitamin D deficiency, and many of those will enjoy longer and much healthier lives (less cancer, diabetes, hypertension, heart disease, multiple sclerosis, osteoporosis, possibly even asthma and depression) as a result of getting proper Vitamin D3 supplementation. With that at stake, I'd just as soon let people who look up Trevor Marshall know that his ideas are not necessarily as well-respected within the mainstream scientific community as some people here might suggest. He certainly deserves to have a bio, but his claims remain *quite* controversial.

Should you have any additional publications or posts or references that align with this subject, of debunking the MP and the theories they support regarding the danger of vitamin D (specifically exogenous sources of vitamin D), please feel free to comment or contact me via e-mail. I also of course welcome any notes that contradict the information I have provided. I'm simply in search of the unbiased, honest truth on the subject. Thanks in advance.

---

One of the claims from Trevor Marshall and the MP camp is that exogenous 25-D from foods and supplements is directly immunosuppressive via it's ability to directly dock to and deactivate the vitamin D nuclear receptor (VDR - an integral nuclear receptor involved in cathelicidin (potent human endogenous antimicrobial agent) gene expression). They support this claim with in-silico computer simulations (which, to my understanding, is not an accurate representation of what is taking place in-vivo, or even in-vitro for that matter.

In a future post I will provide an M.D.'s explanation as to how this claim is incorrect in that there are tight controlling intracellular mechanisms that control conversion & chaperoning of the substrate 25-D and the 1,25OHD active metabolite to the VDR.

Here is a short paper from 2006 that discusses how vitamin D works as a human/mammalian defensin ("Defensin is a generic name reserved for an endogenously synthesized antimicrobial agent") and is integral to the human innate immune system (the branch that targets intracellular pathogens involved in Lyme, Tuberculosis, Chlamydia pneumoniae, mycobacteria, etc.).

Below is an excerpt from the paper that illustrates that in-vitro, limited amounts of the substrate 25-D (which can be obtained exogenously from food and supplements and I believe more indirectly from adequate UV ray exposure) handicap innate immune system components (in this case monocytes & macrophages) from producing the cathelicidin antimicrobial peptide (CAMP) and subsequently killing the mycobacterium tuberculosis.

Vitamin D as a defensin

These data predict that a decrement in the extracellular content of 25-D may be a limiting factor for effective mycobacterium tuberculosis killing. To test this hypothesis Liu and colleagues examined human monocyte-macrophage cathelicidin expression and mycobacterial killing in cells incubated with vitamin D (25-D)-deficient serum from sunlight-deprived African Americans and from a group of vitamin D-sufficient Caucasians. The 25-D-insufficient serum was much less capable of supporting cathelicidin gene expression and bacterial killing than was vitamin D-sufficient serum. However, the significantly diminished cathelicidin and antimicrobial effect of vitamin D-deficient serum on macrophage function could be rescued by restoring the extracellular 25-D levels to normal.

If the hypothesis supported by the MP camp is correct, would we not expect to see reduced CAMP gene expression and reduced mycobaterium killing with the D-sufficient serum? Instead we see the exact opposite; That serum with sufficient (or greater) supplies of 25-D substrate enhances the immune cells' ability to create CAMP and destroy the pathogen, and serum with lower or insufficient supply handicaps the immune cells in battling the pathogen. The 25-D is clearly not binding directly to the VDR and deactivating it, as illustrated by the increased expression of CAMP and pathogen killing, which is dependent on the activated 1,25OHD metabolite, not the 25-D substrate.

Vitamin D Stimulates Hair Growth

Vitamin D3 analogs stimulate hair growth in nude mice

2002 Nov

Cedars-Sinai Medical Center/University of California Los Angeles School of Medicine, Los Angeles, California 90048, USA.

The active form of vitamin D3 can regulate epidermal keratinization by inducing terminal differentiation; and mice lacking the vitamin D receptor display defects leading to postnatal alopecia. These observations implicate the vitamin D3 pathway in regulation of hair growth. We tested the ability of 1,25 dihydroxyvitamin D3 and its synthetic analogs to stimulate hair growth in biege/nude/xid (BNX) nu/nu (nude) mice exhibiting congenital alopecia. Nude mice were treated with different vitamin D3 analogs at doses that we had previously found to be the highest dose without inducing toxicity (hypercalcemia). The mice were monitored for hair growth and were scored according to a defined scale. Skin samples were taken for histological observation of hair follicles and for extraction of RNA and protein. Vitamin D3 analogs dramatically stimulated the hair growth of nude mice, although parental 1,25 dihydroxyvitamin D3 had no effect. Hair growth occurred in a cyclical pattern, accompanied by formation of normal hair follicles and increased expression of certain keratins (Ha7, Ha8, and Hb3). Vitamin D3 analogs seem to act on keratinocytes to initiate hair follicle cycling and stimulate hair growth in mice that otherwise do not grow hair.

Whenever I increase or come back to my D supplementation, I notice positive effects in my hair growth. I know this may sound hard to believe, but when I increase my D, or maintain an adequate daily intake of 4K+ IUs per day, I start to see new hairs popping up in the center of my chest, most noticeably.

Interestingly, they concluded that 1,25D3 did not have any affect. It isn't encouraging to see such a conclusion about regular 1,25D3... but clearly I am proving this to be inaccurate, perhaps, as I'm supplementing with D3 and seeing hair growth, and not with D analogs. Could this mean that my body is also producing these variant analogs, or do we just convert it to regular good old 1,25D3, and this study is mistaken? Or we humans have a different reaction to 1,25D3?

I'm taking this as just another sign that I'm obviously still struggling with D deficiency symptoms when I'm not supplementing. My theory here is that growing new hairs is a sign that I am doing a better job of becoming D replete, and that my cells are desperately sucking up the activated D and engaging in long awaited differentiation activities, now that it has the raw material it needs. Here again is a clear sign that D is upregulating genes in the skin and that the skin and hair follicles harbor a large number of VDRs.

Vitamin D Could Reduce Heart Attack Risk

The mighty "sunshine vitamin" could reduce heart attacks

Dr. Douglass

More good news about vitamin D! Not long ago, I told you that the vitamin D you get from sunlight can help to battle cancer. Now there's yet another killer that this mighty "sunshine vitamin" can help to combat: heart attacks.

According to a new study, men with lower levels of vitamin D are two and a half times as likely to suffer a heart attack. Dr. Edward Giovannucci of the Harvard School of Public Health authored the study and said, "Those with low vitamin D, on top of just being at higher risk for heart attack in general, were at particularly high risk to have a fatal heart attack."

For 10 years, Dr. Edward Giovannucci studied nearly 500 health professionals between the ages of 40 to 75 who'd survived a heart attack. During the same period, he also studied about 1,000 other men who had no history of cardiovascular issues. What he found was that the men who consistently had low levels of vitamin D were the ones most at risk for heart ailments.

"Perhaps having these chronically low levels of vitamin D may be having these subtle physiological changes in a lot of tissues," Dr. Giovannucci said. He added that there are other ways vitamin D can defend against heart diseases: it might lower blood pressure, regulate inflammation, and or reduce respiratory infections in winter.

Of all the vitamins I'm always telling you to pump into your body, vitamin D is one of my all-time favorites. If you've been with me for some time, you already know the highlights of what it can d it prevents falls in the elderly, helps increase lung cancer survival, prevents multiple sclerosis, and helps treat steroid resistant asthma. I imagine the list is only going to get longer as time goes by and more research is done.

As for me, I need no further convincing. I'm heading outside right now.

One thing that is not mentioned here is the theory of association between chronic infection and microbial toxins being poisonous to the heart and circulatory tissue, and thus weakening it and predisposing the individual to cardiovascular disease.

As well as being anti-inflammatory, Vitamin D (25D) is well known to enhance the immune system. By obtaining more vitamin D3 (25D) you're allowing your body to create increasing levels of activated vitamin D (1,25D3) which are essential for producing the human cathelicidin LL-37, which has broad spectrum antimicrobial abilities in the body. It is capable of puncturing holes in pathogens and destroying them. Cathelicidins serve a critical role in mammalian innate immune defense against invasive bacterial infection.

In short, increasing your D levels will also provide you with better immunity against pathogens that could be involved in cardiovascular disease.

Below is yet another study (published June 3, 2008) that illustrates that D3 increases cathelicidin production in skin, and boosts keratinocyte's ability to destroy Staphylococcus aureus. Heard of MRSA?

1,25-dihydroxy vitamin D3 regulates cutaneous innate immune function

Human Cathelicidin is Vitamin D Driven

Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3

Adrian F. Gombart*,1, Niels Borregaard{dagger} and H. Phillip Koeffler*

The innate immune system of mammals provides a rapid response to repel assaults from numerous infectious agents including bacteria, viruses, fungi, and parasites. A major component of this system is a diverse combination of cationic antimicrobial peptides that include the - and ß-defensins and cathelicidins. In this study, we show that 1,25-dihydroxyvitamin D₃ and three of its analogs induced expression of the human cathelicidin antimicrobial peptide (CAMP) gene. This induction was observed in acute myeloid leukemia (AML), immortalized keratinocyte, and colon cancer cell lines, as well as normal human bone marrow (BM) -derived macrophages and fresh BM cells from two normal individuals and one AML patient. The induction occurred via a consensus vitamin D response element (VDRE) in the CAMP promoter that was bound by the vitamin D receptor (VDR). Induction of CAMP in murine cells was not observed and expression of CAMP mRNA in murine VDR-deficient bone marrow was similar to wild-type levels. Comparison of mammalian genomes revealed evolutionary conservation of the VDRE in a short interspersed nuclear element or SINE in the CAMP promoter of primates that was absent in the mouse, rat, and canine genomes. Our findings reveal a novel activity of 1,25-dihydroxyvitamin D₃ and the VDR in regulation of primate innate immunity.

We humans only have one cathelicidin (pronounced cath-i-li-cye-den) antimicrobial peptide, which is known as LL-37 and FALL-39. CAMP is a potent antimicrobial substance that is part of our immune system that is used to destroy pathogens identified in the body, such as bacteria, fungi, parasites, etc. Another recent study I reviewed has informed me that this, our only cathelicidin, is dependent on vitamin D for its production.

Candida & Pathogens Shiver at Iodine

In vitro susceptibility of Candida albicans to four disinfectants and their combinations

Waltimo TM, Orstavik D, Sirén EK, Haapasalo MP.

NIOM, Scandinavivan Institute of Dental Materials, Haslum, Norway. tuomas.waltimo@helsinki.fi

AIM: The aim of this study was to evaluate the susceptibility of seven strains of Candida albicans to four disinfectants: iodine potassium iodide, chlorhexidine acetate, sodium hypochlorite and calcium hydroxide. In addition, all possible pairs of the disinfectants were tested in order to compare the effect of the combination and its components. METHODOLOGY: Filter paper discs were immersed in standardized yeast suspensions and then transferred to disinfectant solutions of different concentrations and incubated at 37 degrees C for 30 s, 5 min, 1 h and 24 h. After incubation the filter paper discs were transferred to vials with PBS and glass beads that were then vigorously shaken for dispersal of the yeast cells. PBS with resuspended yeasts was serially diluted 10-fold. Droplets of 25 microL from each dilution were inoculated on TSB agar plates and incubated in air at 37 degrees C for 24 h. The number of colony-forming units was then calculated from appropriate dilutions. RESULTS: C. albicans cells were highly resistant to calcium hydroxide. Sodium hypochlorite (5% and 0.5%) and iodine (2%) potassium iodide (4%) killed all yeast cells within 30 s, whilst chlorhexidine acetate (0.5%) showed complete killing after 5 min. Combinations of disinfectants were equally or less effective than the more effective component. All C. albicans strains tested showed similar susceptibility to the medicaments tested. CONCLUSIONS: This study indicates that sodium hypochlorite, iodine potassium iodide and chlorhexidine acetate are more effective than calcium hydroxide against C. albicans in vitro. However, combining calcium hydroxide with sodium hypochlorite or chlorhexidine may provide a wide-spectrum antimicrobial preparation with a long-lasting effect.

There are some people that believe that cancer is actually a result of fungal infection. I'm on the fence about this proposal, but if these were to be true, it could partially explain the reason that the mainland Japanese who reportedly consume up to 100x the US RDA of iodine daily (from seaweed, ocean foods, etc.) suffer from some of the lowest levels of breast cancer and cancer of female reproductive organs.

Iodine is a known potent antimicrobial substance against yeast, fungus, bacteria, and viruses.

The End of Antibiotics and the Rise of Iodine as an Effective Alternative

Iodine offers a serious and potent replacement for much of the antibiotics that are literally destroying people's lives and can be used safely with children. Parents, who chose not to dose their kids with dangerous vaccines will be glad to know that iodine can be very effective against a host of viral infections that medical officials insist threaten children.

Though it kills 90 percent of bacteria on the skin within 90 seconds, its use as an antibiotic has been ignored. Iodine exhibits activity against bacteria, molds, yeasts, protozoa, and many viruses; indeed, of all antiseptic preparations suitable for direct use on humans and animals and upon tissues, only iodine is capable of killing all classes of pathogens: gram-positive and gram-negative bacteria, mycobacteria, fungi, yeasts, viruses and protozoa. Most bacteria are killed within 15 to 30 seconds of contact.

Iodine is by far the best antibiotic, antiviral and antiseptic of all time - Dr. David Derry

Dr. Derry says that iodine is effective "for standard pathogens such as Staphylococcus, but also iodine has the broadest range of action, fewest side effects and no development of bacterial resistance." There is a world of difference between using an antibiotic – anti-life substance – and an antibiotic, antiviral and antifungal substance like iodine, which is life serving because it is a basic and most necessary nutritional substance.

Iodine kills single celled organisms by combining with the amino acids tyrosine or histidine when they are exposed to the extra-cellular environment. All single cells showing tyrosine on their outer cell membranes are killed instantly by a simple chemical reaction with iodine that denatures proteins. Nature and evolution have given us an important mechanism to control pathogenic life forms and we should use it and trust it to protect us in ways that antibiotics can't.

Additionally...

Iodine: The Candida Killer

Perhaps the world's cheapest, most traditional, and best anti Candida agent is the simplest. It is iodine. Yes, I am describing the same iodine found in "tincture of iodine" that your mother used to treat your cuts and scratches when you were a child. Because Big Pharma drug companies have re-educated us to believe that the fancy new (expensive) antibiotics are better and safer than (dirt cheap) iodine, we have lost sight of the one truly miraculous and completely natural antiviral, antibiotic and antifungal agent. Nothing is likely to beat iodine in this regard.

Iodine is like the complete package! Information like this is one of the reasons I've become very interested in iodine.