The Importance of Vitamin D3

The Importance of Vitamin D3

 Recent studies suggest the importance of Vitamin D3 in immunity, and indeed, vitamin D3 deficiency has been linked to multiple sclerosis, rheumatoid arthritis, hypertension, heart disease, depression, diabetes, chronic pain, osteoporosis and many other illnesses:

 

Vitamin D3 has also been shown to play an important role in host defense against pathogens by promoting the production of the human antimicrobial peptides, cathelicidins (LL-37). These cathelicidins have been found to have broad spectrum antimicrobial activity, showing activity against a variety of pathogens. While cathelicidins (LL-37) have been shown to have little or no direct effect against C. pnuemoniae, Vitamin D3 has been shown to disrupt the mechanism that the intracellular forms of C. pneumoniae use to prevent normal celluar apoptosis, and it is believed that Vitamin D3 is active against the intracellular forms of C. pneumoniae through this mechanism. The resulting die-off effects from Vitamin D3 can be quite large, and symptoms of secondary pophryia can also be dramatically increased. Vitamin D3 levels should therefore be increased very slowly when treating a C. pneumoniae infection!  

Red Sat, 2009-02-21 13:17

Vitamin D3 Table of Contents

Vitamin D3 Table of Contents Guest (not verified) Mon, 2009-02-23 21:22

Vitamin D3, Cathelicidins, and Infection

Vitamin D3, Cathelicidins, and Infection

 Vitamin D3 has also been shown to play an important role in host defense against pathogens by promoting the production of the human antimicrobial peptides, cathelicidins (LL-37).

 These cathelicidins have been found to have broad spectrum antimicrobial activity, showing activity against the following microbes, among others:

A couple of other important and apparently previously unrecognized functions of of the cathelicidins (LL-37) upregulated by Vitamin D3 are its effects on bacterial biofilm formation and eradication and its effects on secondary necrosis of neutrophils:

Studies on Vitamin D3 and cathelicidins in septicemia suggest that they may also play an important role in protection against septicemia.   Recent articles attribute their  "primary effect in reducing the risk of septicemia to other effects of cathelicidins, including lower endotoxin and proinflammatory cytokinei tumor necrosisi factor α levels in plasma, as well as reduced endotoxic shock and death":

 While cathelicidins (LL-37) have been shown to have little or no direct effect against C. pnuemoniae, Vitamin D3 has been shown to disrupt the mechanism that the intracellulari forms of C. pneumoniae use to prevent normal celluar apoptosisi, and it is believed that Vitamin D3 is active against the intracellular forms of C. pneumoniae through this mechanism:

 The resulting die-off effects from Vitamin D3 can be quite large, and symptoms of secondary pophryia can also be dramatically increased. Vitamin D3 levels should therefore be increased very slowly when treating a C. pneumoniae infection!    

Red Sat, 2009-02-21 13:42

Vitamin D3, Defensins, and Infection

Vitamin D3, Defensins, and Infection

 

Studies seem to suggest that Vitamin D3 plays an important role in production of  Defensins, just is it apparently does with the more widely discussed antimicrobial peptides, Cathelicidins (LL-37):

 While less discussed than their antimicrobial "cousins", cathelicidins, studies suggest that Alpha and Beta Defensins also play an important role in host defense.   Here are a few such studies: Alpha Defensins (also knowns as Neutrophil Defensins):

 Beta Defensins:

  Here's an excellent article on the various currently identified defensins and their molecular mechanisms of action:

   Studies suggest that in addition to their antimicrobial effects, defensins may also play an important role in regulating immune responses and inflammation, as well as in wound repair:

Red Sat, 2009-06-06 15:03

Cathelicidins, Defensins and their Important Interactions with Leukotriene B4

Cathelicidins, Defensins and their Important Interactions with Leukotriene B4

 Studies suggest that human cathelicidins (LL-37) and Leukotriene B4 may work in a positive feedback loop, meaning they may both stimulate each other for enhanced immunei response:

And several studies suggest that Leukotriene B4, cathelicidins and defensins indeed play a very important role together in controlling infections:

 Many herbal supplements and prescription and non-prescription drugs are known to block production of Leukotriene B4 either by inhibiting all downstream leukotriene products of the 5-Lipoxygenase (5-LOX) pathway or by blocking Leukotriene B4 (LTB4) directly.   Below is a list of several herbal supplement or prescription and non-prescription drugs that studies suggest may inhibit the 5-LOX pathway or block LTB4 directly: 

Prescription and Non-Prescription Drugs:

 Herbal Sources:

   

Red Sat, 2009-02-21 14:09

Vitamin D3 and the Importance of IL-15

Vitamin D3 and the Importance of IL-15

Here's another interesting area to keep an eye on, namely the apparent importance of IL-15 for bioconversion of 5-hydroxyvitamin D3 (25D3) into bioactive 1,25D3 and the downstream induction of cathelicidins:

"In this study, we found that TLR2/1-induced IL-15 was required for induction of CYP27b1, the VDR and the downstream antimicrobial peptide cathelicidin.  Although both IL-15 and IL-4 triggered macrophage differentiation, only IL-15 was sufficient by itself to induce CYP27b1 and subsequent bioconversion of 25-hydroxyvitamin D3 (25D3) into bioactive 1,25D3, leading to VDR activation and induction of cathelicidin" Here's another study along these lines:

"Together, these results demonstrate that IL-15 plays an important role in antigen-induced neutrophil migration during inflammationi, triggering a sequential OVA, IL-15, IL-18, MIP-2, MIP-1alpha, TNF-alpha, LTB4 and neutrophil migration signaling cascade"  There are quite a few other studies in pubmed showing the importance of IL-15 in fighting infectionsi.  Here are a couple:

Unfortunately, some drugs seem to inhibit IL-15, and researchers are on the hunt for additional IL-15 inhibitors to treat "inflammatory" diseasesi:

   

Red Sat, 2009-02-21 16:51

Vitamin D3 in Chlamydia pneumoniae Infection - Important effects on apoptosis

Vitamin D3 in Chlamydia pneumoniae Infection - Important effects on apoptosis

 Studies have shown that Cpn inhibits apoptosis by interfering with with cytochrome c release and caspase activation:

 Studies also suggest that Vitamin D3, or more specifically, the antimicrobial peptides, cathelicidins (LL-37)  induces apoptosis of  infected cells "via enhanced LL-37-induced mitochondrial membrane depolarisation and release of cytochrome c, with activation of caspases -9 and -3":

   Studies also suggest that Cpni interferes with NF-KappaB regulation via "degradation of BH3-only proteins such as Bim, Puma, Bad, Bik, Bmf, Noxa, and tBid, which inhibit proapoptotic Bax and Bak.":

The following study seems to go one step further and suggests that in Cpn: "Persistent infection resulted in the upregulation of the NF-kappaB regulated inhibitor of apoptosisi protein 2 (cIAP-2) but not inhibitor of apoptosis protein 1 (cIAP-1)".  However, the study also suggests "silencing of either cIAP-1 or cIAP-2 sensitized infected cells [or causes apoptosis in other words, I believe] suggesting that IAPs play an important role in the apoptosis resistance of persistently infected cells":

 Apparently this action occurs directly through Vitamin D Receptors (VDRs) on numerous cell types in the body.   Here are a few articles discussing VDR signalling and NF-KappaB activation in various cell types:

 The resulting die-off effects from Vitamin D3 can be quite large, and symptoms of secondary pophryia can also be dramatically increased. Vitamin D3 levels should therefore be increased very slowly when treating a C. pneumoniae infection! It is also through its effects on NF-KappaB, that Vitamin D is believed to play a beneficial role in the prevention of and potentially treatment of, cancers:

   

Red Sat, 2009-02-21 14:47

Vitamin D3 and its Other Mechanisms for Controlling Infections

Vitamin D3 and its Other Mechanisms for Controlling Infections

 In addition to its importance for inducing antimicrobial peptides, studies suggest that Vitamin D may help control infections through other mechanisms.   The following study suggests that Vitamin D may be important for controlling intracellular infections by down-regulating tryptophan-aspartate-containing coat protein (TACO) gene expression:

  

Red Sat, 2009-02-21 17:15

Vitamin D3 and Barrier Integrity

Vitamin D3 and Barrier Integrity Red Sat, 2009-02-21 16:00

Vitamin D3 and Nervous System Repair

Vitamin D3 and Nervous System Repair

 Studies suggest that Vitamin D is important for nervous system function and repair.   Some important studies include:

The above article contains an amazingly complete and fairly easy to read review of the known actions of Vitamin D in the body, including very good explanations of the known pathways.   The following section is particularly relevant:

Section 5.2 Effects of Vitamin D on the Nervous System - this section, I believe, is a must read for those with CNS issues related to Cpn.  Some points of interest:

  • Vit D "participates in modulation of CNS detoxification pathways through regulation of y-Glutamyl transpeptidase, an enzyme which up-regulates the glutathione pool and reduces the production of reactive nitrogen species in astrocytes"
  • Vit D "may inhibit the synthesis of inducible nitric oxide synthase (iNOS), an enzyme which is produces in response to inflammatory stimuli and have harmful effexts on the CNS"
  • Vit D "may protect the structure and integrity of neurons through neurotrophin (NT) synthesis and nerve growth factor (NGF)"

More studies along these lines from as early as 1991:

   

Red Sat, 2009-02-21 16:59

Vitamin D3 and its Effects on Human Diseases

Vitamin D3 and its Effects on Human Diseases

Recent studies suggest the importance of Vitamin D3 in immunity, and indeed, vitamin D3 deficiency has been linked to multiple sclerosis, rheumatoid arthritis, hypertensioni, heart diseasei, depression, diabetes, chronic pain, osteoporosis and many other illnesses:

 

A recent study suggests the genetic importance that Vit D3 plays in the role of human and other primate immunity:

     Here is the full article:

 By the way, although I believe articles such as the one above make an important case for the involvement of low levels of Vitamin D3 in the pathogenesis of Multiple Sclerosis and other "autoimmune" diseases, IMHO, the expert researchers on Vitamin D3 may also be missing much of the reason for this, namely the importance of Vitamin D3 in controlling or preventing the infections that have been linked with these diseases.   These articles often mention the antimicrobial peptides (cathelicidins) that so require Vit D3 for their production, but they really only mention these cathelicidins in reference to overt infections.   These articles also often mention Vit D3's importance for normal cellular apoptosis, but again they usually only mention this in reference to cancer.   IMHO, these researchers may be missing the importance of these two (and probably other) effects of Vit D3 in in controlling infections that may cause disease.   As we are aware, Vit D3 may influence levels of Chlamydia pneumoniae infection through its effects on the ability of the Chlamydia pneumoniae to prevent apotosis (and replicate protected inside a cell) for instance.   And cathelicidins may be important in keeping the henchmen Herpes viruses dormant, where they belong. Although I have no medical background, I personally believe the pathogenesis of many of the "autoimmune" diseases that these researchers point to heavy involvement of low levels of Vit D3 in their pathogenesis may actually be far more complex than these researchers realize - namely that infections play a major role in disease pathologies and Vit D is crucial in controlling these infections.    Still, bless these researchers for the efforts!

Red Sat, 2009-02-21 15:15

Vitamin D3 and "Autoimmune" and Rheumatic Disease

Vitamin D3 and "Autoimmune" and Rheumatic Disease

Below are some articles discussing the beneficial effects of Vitamin D in "Autoimmune" and Rheumatic Disease:

 Additional articles on Vitamin D in Autoimmune Disease can be found on the Vitamin D Council page on Vitamin D and Autoimmune Illness:

 

Red Sat, 2009-02-21 15:18

Vitamin D3 and Multiple Sclerosis

Vitamin D3 and Multiple Sclerosis

 A number of articles and studies suggest that Vitamin D provides benefit in the prevention and treatment of Multiple Sclerosis:

While most studies that suggest Vit D3 is beneficial in Multiple Sclerosis are epidemiological in nature, a recent open study of 12 patients by Kimball, et al found that the number of lesions per patient (assessed with a nuclear magnetic brain scan) decreased in a high-dose Vitamin D3 treatment group from the initial mean of 1.75 to the end-of-study mean of 0.83:

Studies suggest that Vitamin D may provide benefit in Multiple Sclerosis through several different mechanisms.   First Vit D provides antimicrobial benefits, again through several mechanisms:

 Vitamin D also downregulates inflammation and many of the downstream tissue-destroying products that have been shown via studies to play such an important role in Multiple Sclerosis:

 And importantly, studies also suggest that Vitamin D plays an important role in nervous system function and repair:

  Numerous other studies on the beneficial effects of Vitamin D in Multiple Sclerosis can be found on the Vitamin D Council page on Vitamin D and Multiple Sclerosis:

   

Red Sat, 2009-02-21 16:23

Vitamin D3 and Heart Disease

Vitamin D3 and Heart Disease

 A number of articles and studies suggest that Vitamin D provides benefit in the prevention and treatment of Heart Disease:

The following article provides an overview of some of the suspected roles that Vitamin D3 may play in Heart Disease.  They are that Vitamin D3:

  1. Is anti-inflammatory
  2. Is anti-thrombotic
  3. Reduces plaque instability through its effects on MMPs, TIMP-1 and C-reactive Protein
  4. Reduces blood pressure and plasma renin activity
  5. Regulates nitric oxide production

Below are a few supporting studies for each of the suspected roles Vitamin D3 may play in Heart Disease as discussed in the article above:

Is anti-inflammatory:

 

Is anti-thrombotic:

 Reduces plaque instability through its effects on MMPs, TIMP-1 and C-reactive Protein:

Reduces blood pressure and plasma renin activity:

Regulates nitric oxide production:

   A recent study suggests that Vit D3 may also play an important roll in preventing foam cell formation:

   An excellent, and easy to understand video on Vitamin D and Cardiovascular Disease can be found here:

   Additional articles on Vitamin D and Heart Disease can be found on the Vitamin D Council's Vitamin D and Heart Disease and Hypertension pages:

    

Red Sat, 2009-02-21 18:03

Vitamin D3 and Cancer

Vitamin D3 and Cancer

 Studies suggest that Vitamin D may play an important role in the prevention and potentially even treatment of many forms of cancer.   A recent four-year, randomized study at Creighton University following 1,179 healthy, postmenopausal women from rural eastern Nebraska, found that daily supplementation with only 1,100 iu of Vitamin D led to up to 77% fewer cases of all forms of Cancer:

Here's an easy to read summary article:

And the full study:

 Studies also suggest that Vitamin D levels may be an important predictor of cancer survival and even cancer relapse rates:

Here's an easy to read summary article:

And the cited summary articles:

  The slide found @ minute 26 in the following presentation by Dr David Feldman, MD at Stanford provides an excellent overview of some of the currently suspected mechanisms of anti-cancer activities of Vitamin D3. They are:

  1. Inhibits G1/G0 cell cycle arrest
  2. Stimulates apoptosis
  3. Stimulates differentiation
  4. Regulates tumor suppressors / oncogenes
  5. Regulates growth factors or receptors
  6. Is anti-angiogenic
  7. Inhibits invasion and metastasis
  8. Is anti-inflammatory

BTW, this is a great video on the importance of Vitamin D3, and it includes a very good discussion on the Vitamin D pathways in general. Towards the end (@ the 20 minute mark), it discusses Vit D3 in relation to cancer, including a nice up-to-date list of the suspected mechanisms involved as copied above.

 Below are a few supporting studies for each of the mechanisms of anti-cancer activity of Vit D3 discussed in the video above:

Inhibits G1/G0 cell cycle arrest:

 Stimulates Apoptosis:

Stimulates differentiation:

 

Regulates tumor suppressors / oncogenes:

 

Regulates growth factors or receptors:

 Is anti-angiogenic:

  Inhibits invasion and metastasis:

 

Is anti-inflammatory:

    Vitamin D3 has also been shown to have anti-cancer effects through other mechanisms: 

  1. Cancerous cells have been shown to require telomerase in order to survive (and avoid apoptosis) as the following article discusses:

"In 90 percent of cancers, no matter what caused the cancer to form, it needs telomerase activity to maintain the cell. Without telomerase, the cell will die." And Vitamin D3 has been shown to downregulate telomerase in several forms of cancer:

 

 

Here's another great video on Vitamin D3 and cancer.  Pay particular attention to the discussion on the potential involvement of Tight Junctions and Adherins in cancer development and progression starting @ minute 20:00:

  

Additional studies suggesting the role Vitamin D3 plays in cancer can be found on the Vitamin D Council page on Vitamin D and Cancer:

Red Sat, 2009-02-21 18:10

Vitamin D3 and Inflammatory Bowel Disease

Vitamin D3 and Inflammatory Bowel Disease

 Studies suggest that Vitamin D and the it's downstream Antimicrobial Peptides (AMPS) products may have beneficial effects in Inflammatory Bowel Disease (IBD):

Don't miss this excellent summary table in the above article:
Table 1Table 1-Antimicrobials in the gastrointestinal tract.

 And while epidemiological studies do not necessarily point to a root cause, the studies below are interesting in that they seem to find that Inflammatory Bowel Disease occurs at higher rates in northern latitudes and also increases with affluence (whereby you might assume with greater affluence, people may spend more time indoors, etc):

 Lastly, below is an article on a recent study that discusses just how complicated the whole disease process for Inflammatory Bowel Disease may really be, namely that it may take genetic susceptibility (and potentially low Vitamin D levels) and then potentially even something like a virus (in this case Norovirus) that can alter the gut microbe balance before disease occurs:

Here's a link to the actual study referenced above:

Additional articles on Vitamin D in Inflammatory Bowel Disease can be found on the Vitamin D Council page on Vitamin D and Inflammatory Bowel Disease:

Red Sun, 2011-01-09 13:04

Vitamin D3 and Mental Health

Vitamin D3 and Mental Health Red Sat, 2009-02-21 19:26

Vitamin D3 and Chronic Pain

Vitamin D3 and Chronic Pain Red Sat, 2009-02-21 15:34

Vitamin D3 and Thyroid Disease

Vitamin D3 and Thyroid Disease

 Below are articles discussing the beneficial effects of Vitamin D in Thyroid Disease:

 

Below is the full study article.  While the article focuses on Graves' hyperthyroidism, the discussion and conclusion sections list some interesting findings of recent research on Vitamin D3's importance for proper thyroid function in general.   It's well worth a read:

 

Red Sat, 2009-02-21 15:27

Vitamin D3 and its Effects on Matrix Metalloproteinase (MMP) Production

Vitamin D3 and its Effects on Matrix Metalloproteinase (MMP) Production Red Sat, 2009-02-21 17:48

Vitamin D3 and the Importance of Magnesium

Vitamin D3 and the Importance of Magnesium Red Sat, 2009-10-03 13:02

Vitamin D3 Supplementation and Testing

Vitamin D3 Supplementation and Testing

 There is much controversy surrounding the optimum levels of Vitamin D3 supplementation, and while the currently established safe upper limit for Vitamin D3 is listed as 2000 IU per day for adults and children over the age of 12 months, many experts are now questioning this level and calling for the upper limit to be increased to levels as high as 10,000 IU:

Another method to obtain adequate levels of Vitamin D3 is through approximately 15-20 minutes of near full body exposure to the sun at peak sun times during the summer. In this amount of time at peak sun during peak sun months, our skin produces between 10,000 and 20,000 IU of Vitamin D3. No additional Vitamin D3 is produced in longer exposure, and peak levels are produced prior to any sunburn pinkness. However, the time of the day, the season of the year, and the latitude you live in alter the the amount of UVB rays (the Vitamin D3 producing rays) you are exposed to as the following study from India points out:

 Even at high noon, UVB exposure varies so much by season, that you may have trouble getting enough Vitamin D3 in the near winter and winter months depending on your latitude as the diagrams of UVB exposure in various US cities by month in the following article show:

 Vitamin D3 supplementation may be contraindicated in certain diseases including sarcoidosis, so please talk to your doctor before taking high level supplements of Vitamin D3.  Some great articles related to dosing and testing for Vitamin D3 include:

Note the discussion on the prescription form of Vit D (Vit D2) and the resulting unnatural metabolic by-products in the 2nd to last paragraph on page 13.  Here's the article that the above article refers to in support of Vit D3 over Vit D2:

  There are multiple test methods for measuring 25(OH)D levels.   The DiaSorin RIA method is the standard that has been used in most research studies so it is important to get tested via a lab that uses a testing method that returns results that are well calibrated to the DiaSorin RIA standard so results can be compared equally with the results found in these studies:

This article, from ZRT Laboratory, has some additional information on the differences in the three most common testing methods for 25(OH)D:

 Relatively inexpensive home self tests  for Vitamin D levels - 25(OH)D tests - are available from the following links, and these tests apparently are endorsed by many of the experts in the field of Vitamin D:

And members of CpnHelp have been posting and tracking their 25(OH)D levels on the following thread:

 

Red Sat, 2009-02-21 17:38

Vitamin D3 and the Importance of Zinc

Vitamin D3 and the Importance of Zinc

 While interactions between Vitamin D and Zinc are not well studied, Vitamin D Receptors (VDRs) are known to have zinc fingers in their DNA binding domains: 

  And studies seem to suggest that zinc is important for proper Vitamin D Receptor function: 

  Studies also seem to suggest that zinc is very important in the immune response against infections: 

Here's a news article on a recent study suggesting that zinc induces higher T cell activation, important for fighting viral and bacterial infections:

 

Here's the study summary article:

 

 Other studies also seem to support these findings:

  

Red Sat, 2009-10-10 13:14

Some Great Articles on the the Numerous Effects of Vitamin D3 in the Body

Some Great Articles on the the Numerous Effects of Vitamin D3 in the Body

 Below are some great articles on the numerous effects that Vitamin D3 is believe to have on the body:

By the way, although I believe the above articles make an important case for the involvement of low levels of Vitamin D3 in the pathogenesis of Multiple Sclerosis and other "autoimmune" diseases, IMHO, the expert researchers on Vitamin D3 may also be missing much of the reason for this, namely the importance of Vitamin D3 in controlling or preventing the infections that have been linked with these diseases.   These articles often mention the antimicrobial peptides (cathelicidins) that so require Vit D3 for their production, but they really only mention these cathelicidins in reference to overt infections.   These articles also often mention Vit D3's importance for normal cellular apoptosis, but again they usually only mention this in reference to cancer.   IMHO, these researchers may be missing the importance of these two (and probably other) effects of Vit D3 in in controlling infections that may cause disease.   As we are aware, Vit D3 may influence levels of Chlamydia pneumoniae infection through its effects on the ability of the Chlamydia pneumoniae to prevent apotosis (and replicate protected inside a cell) for instance.   And cathelicidins may be important in keeping the henchmen Herpes viruses dormant, where they belong. Although I have no medical background, I personally believe the pathogenesis of many of the "autoimmune" diseases that these researchers point to heavy involvement of low levels of Vit D3 in their pathogenesis may actually be far more complex than these researchers realize - namely that infections play a major role in disease pathologies and Vit D is crucial in controlling these infections.    Still, bless these researchers for the efforts!     

Red Sat, 2009-02-21 14:58

Some Great Video and Audio files on the Importance of Vitamin D3

Some Great Video and Audio files on the Importance of Vitamin D3 Red Sat, 2009-02-21 13:25

Vitamin D3, Demographic Trends & Statistics

Vitamin D3, Demographic Trends & Statistics

 Below are some demographic trends and statistics on Vitamin D3 levels in the general population:  

 

Red Sun, 2009-04-12 13:11