Re: Vitamin D3 & Proteotoxicity in HUMANs? TGFß-1 -NOD2 - IGF-1 -- LPS - BRAIN FOG - VDR -CYP27B1 --LL37 -- Go FISH?
randall
> x-no-archive: yes
>
> http://www.fasebj.org/cgi/content/full/15/14/2579
>
> Vitamin D: its role and uses in immunology 1
>
> HECTOR F. DELUCA2 and MARGHERITA T. CANTORNA*
> Department of Biochemistry, University of Wisconsin-Madison, Madison,
> Wisconsin 53706, USA; and
> * Department of Nutrition, Pennsylvania State University, University
> Park, Pennsylvania 16802, USA
>
> 2Correspondence: Department of Biochemistry, University of
> Wisconsin-Madison, 433 Babcock Dr., Madison, WI 53706-1544, USA. E-mail:
> del...@biochem.wisc.edu
>
> In recent years there has been an effort to understand possible
> noncalcemic roles of vitamin D, including its role in the immune system
> and, in particular, on T cell-medicated immunity. Vitamin D receptor is
> found in significant concentrations in the T lymphocyte and macrophage
> populations. However, its highest concentration is in the immature
> immune cells of the thymus and the mature CD-8 T lymphocytes. The
> significant role of vitamin D compounds as selective immunosuppressants
> is illustrated by their ability to either prevent or markedly suppress
> animal models of autoimmune disease. Results show that
> 1,25-dihydroxyvitamin D3 can either prevent or markedly suppress
> experimental autoimmune encephalomyelitis, rheumatoid arthritis,
> systemic lupus erythematosus, type I diabetes, and inflammatory bowel
> disease. In almost every case, the action of the vitamin D hormone
> requires that the animals be maintained on a normal or high calcium diet.
>
> Possible mechanisms of suppression of these autoimmune disorders by the
> vitamin D hormone have been presented. The vitamin D hormone stimulates
> transforming growth factor TGFß-1 and interleukin 4 (IL-4) production,
> which in turn may suppress inflammatory T cell activity. In support of
> this, the vitamin D hormone is unable to suppress a murine model of the
> human disease multiple sclerosis in IL-4-deficient mice. The results
> suggest an important role for vitamin D in autoimmune disorders and
> provide a fertile and interesting area of research that may yield
> important new therapies.—DeLuca, H. F., Cantorna, M. T. Vitamin D: its
> role and uses in immunology.
Susan,
This LINK is so you can take credit for the hPa-axis. LOL
Nothing KNEW under that SUN. <G>
Will i swallow my pride or tail?
Uroborus
http://en.wikipedia.org/wiki/Ouroboros
Simply MORE of the infernal return of evil skin under the
paternalistic SUN?
OK, i'll play the game.
Let's digest the TERMs...
TGF certainly brings up some xlnt threads in this group.
Like 512 returns for TGF in the P NG:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=tgf
The first thread in this search: inner/outer crap has 20 hits for TGF:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/af2fbee3f5030077
But, but, what if some folks age quicker due to D3 or NOD2 some how?
Like HOW, brown COW?
HEART ATTACKs?
A nod to nod2 i suPPose?
http://en.wikipedia.org/wiki/NOD2
There is monkey business a FOOT, Dr. Watson.
OK, how does VDR fly over the cuckoo's NeST my FOUL psor bRAIN? lol
Those hockey pucks up in Canada are more sun dePrived then equatorial
denizens.
Is that why they play hockey?..... for the exercise?
Let's ask THEM...
www.ncbi.nlm.nih.gov/pubmed/19948723
Biol Chem. 2009 Nov 30.
Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/
CARD15-beta defensin 2 innate immune pathway defective in Crohn's
disease.
Wang TT, Dabbas B, Laperriere D, Bitton AJ, Soualhine H, Tavera-
Mendoza LE, Dionne S, Servant MJ, Bitton A, Seidman EG, Mader S, Behr
MA, White JH.
McGill University, Canada;
Vitamin D signaling through its nuclear vitamin D receptor (VDR) has
emerged as a key regulator of innate immunity in humans. Here we show
that hormonal vitamin D, 1,25-dihydroxyvitamin D3 (1,25D) robustly
stimulates expression of pattern recognition receptor NOD2/CARD15/IBD1
gene and protein in primary human monocytic and epithelial cells. The
VDR signals through distal enhancers in the NOD2 gene, whose function
was validated by chromatin immunoprecipitation and chromatin
conformation capture assays. A key downstream signaling consequence of
NOD2 activation by agonist muramyl dipeptide (MDP) is stimulation of
NF-kappaB transcription factor function, which induces expression of
the gene encoding antimicrobial peptide beta defensin 2 (DEFB2/HBD2).
Pretreatment with 1,25D synergistically induced NF-kappaB function and
expression of genes encoding DEFB2/HBD2 and antimicrobial peptide
cathelicidin in the presence of MDP. Importantly, this synergistic
response was also seen in macrophages from a donor wild-type for NOD2,
but was absent in macrophages from patients with Crohn's disease
homozygous for non-functional NOD2 variants. These studies provide
strong molecular links between vitamin D deficiency and the genetics
of Crohn's disease, a chronic incurable inflammatory bowel condition,
as Crohn's pathogenesis is associated with attenuated NOD2 or DEFB2/
HBD2 function.
PMID: 19948723
NOD2 snp's do bring up that craPPy disease, CROHN's.
http://www.pennlive.com/bodyandmind/index.ssf/2009/11/midstate_plays_key_role_in_gen.html
And we know psor folks are FULL of craP. LOL
Just like the craPPy thing haPPening in the gut linings of crohn's
people.
http://content.nejm.org/cgi/content/short/361/21/2066
[...]
NOD2 protein is an intracellular sensor of bacterial peptidoglycan,
and autophagy enables cells to regulate and degrade diverse
intracellular components
<sniP>
http://en.wikipedia.org/wiki/Peptidoglycan
And you KNOW what that brings uP?
No what?
LPS (cell wall of endogenous endotoxin)... duh.
http://en.wikipedia.org/wiki/Cell_wall#Bacterial_cell_walls
How much craP is there in psor folks?
Boy that's a loaded question. <W>
OK... this is a fishy toPic... btw...
And with sweet whey.... how i've stayed so extraordinarilly CLEAR. LOL
But, but, what is the gut, VDR, D3 and Ai (psoriasis) connections?
Is it all due to NOD2 not being able to return homeostasis and to much
endotoxin building up in the system and/or making plaque some how on
the skin?
[randall note: major segue coming]
How about a short, JRX, Susan and i segue?
LOL
We all talked some smack BACK on April 6th, 2007
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/cda0713cbe6cd423
Which brought uP BRAINs and IGF-1 in that teeter totter of HOMEOstasis
like thread.
But aging is the kicker in the ifg-1 pathway THESE days?
Everyone wants to live forever.
Or what seems like it. LOL
But why igf?
It's so close to hPa-axis one MAY suPPose?
IGF-1 signal pathway
http://en.wikipedia.org/wiki/Insulin-like_growth_factor_1
Insulin-like growth factor 1 (IGF-1), which was once called
somatomedin C, is a polypeptide protein hormone similar in molecular
structure to insulin. It plays an important role in childhood growth
and continues to have anabolic effects in adults.
<sniP>
Front page of my local paPer today.
http://www.signonsandiego.com/news/2009/dec/12/clue-alzheimers-slow-down-aging/
Clue for Alzheimer’s: Slow down aging
S.D. researchers’ study on mice shows promise
By Thomas KuPPer, UNION-TRIBUNE STAFF WRITER
Saturday, December 12, 2009 at 1:37 a.m
A team of San Diego researchers has found that the key to stopping
Alzheimer’s disease may be slowing down the aging process.
That may seem obvious, given that Alzheimer’s predominately strikes
older people. But the scientists say their work sheds light on a
fundamental question: whether Alzheimer’s is a consequence of the
aging process itself or whether the substances in the brain that are
believed to cause the disease just take a long time to form.
The study, published yesterday in the journal Cell, looked at whether
altering a molecular mechanism known to slow aging in mice would also
slow the onset of the disease. It turned out mice whose aging process
had been slowed did much better in navigating a water maze and other
tests.
“Our study opens up a whole new avenue of looking at the disease,”
said the lead scientist, Andrew Dillin of the Salk Institute for
Biological Studies. “Looking at the way we age may actually have more
impact on the treatment and prevention of Alzheimer’s disease than
studying the basic biology of the disease itself.”
The big question, as with any early-stage research, is whether the
work has relevance in humans. While it’s impossible to say for sure,
Dillin said one reason for encouragement is that the pathway he
studied is believed to work similarly in humans and mice.
Dillin has already helped start a company, Massachusetts-based
Proteostasis Therapeutics, that is looking at whether regulating
various signaling pathways could slow the course of a range of
diseases. The company has raised $45 million in venture capital but is
still at the discovery stage.
Another important question is whether slowing down the aging process
is important in blocking other diseases in which age appears to play a
role, such as cancer.
“Interestingly,” Dillin said, “three studies found that some very long-
lived humans carry mutations in components of the IGF-1 signal pathway
— the same pathway that we perturbed to increase the life span of the
mice in our study.”
Dillin’s team, which includes scientists from the University of
California San Diego and La Jolla’s Scripps Research Institute, has
been on the project for about five years.
The foundation of their work is the IGF-1 pathway, for insulin-like
growth factor, which is known to play a role in aging. Other studies
have shown that if you could lower the activity of this pathway, you
could extend life.
Dillin hypothesized that in addition to extending life, you could also
postpone Alzheimer’s and possibly other diseases that sometimes
accompany old age. The ultimate payoff would be to find ways to help
people stay disease-free farther into their lives.
The researchers focused on Alzheimer’s, a condition for which age is
the major risk factor. Beyond age 65, the number of people with the
disease doubles every five years.
“We went directly to the root cause of Alzheimer’s disease and asked
whether we could influence the onset of the disease by modulating the
aging process,” said Ehud Cohen, a former postdoctoral researcher in
Dillin’s lab who is now on the faculty of Hebrew University-Hadassah
Medical School in Israel.
Of the hundreds of mice in the study, the scientists created some in
which IGF-1 activity was cut in half. Those mice lived up to 35
percent longer than normal mice.
Cohen then employed behavioral tests to find out whether it was aging
or simply the passage of time that determined the onset of Alzheimer’s
disease. By nine months of age, he said, the behavioral differences
were apparent.
But Cohen said one surprise came when he looked at the plaques in the
brain that are typically a telltale sign of Alzheimer’s disease.
Although the long-lived mice in the study tended not to show any of
the cognitive or behavioral impairments typical of Alzheimer’s
patients, their brains were riddled with highly compacted plaques.
That suggests that the role of the plaques may be different from what
has been believed.
<sniP>
Got to love the SALK institute:
http://en.wikipedia.org/wiki/File:Salk_Institute_Panorama.jpg
LOADs of people get a TAN via UVB's all over at blacks beach just
below the salk institute:
http://en.wikipedia.org/wiki/Black's_Beach#Black.E2.80.99s_Beach_Nude_Beach_Status
A pic of pale faces:
http://jillsorenson.com/blog/uploads/blacksbeach.jpg
Getting naked for peace at blacks beach
http://www.barewitness.org/photoalbum/LaJolla2.htm
This is an iconic shot of the salk
http://www.nexusjournal.com/2008/Images/Salk_Institute.jpg
And as a matter of interest, the developer has the same name as the
architect.
I'll locate Dillin's scriPPs SALK abstract:
Here it is:
www.ncbi.nlm.nih.gov/pubmed/19701939
Protein Sci. 2009 Nov;18(11):2231-41.
A kinetic assessment of the C. elegans amyloid disaggregation activity
enables uncoupling of disassembly and proteolysis.
Bieschke J, Cohen E, Murray A, Dillin A, Kelly JW.
Department of Chemistry, The Skaggs Institute for Chemical Biology,
The Scripps Research Institute, La Jolla, California 92037, USA.
Protein aggregation is a common feature of late onset
neurodegenerative disorders, including Alzheimer's disease. In
Alzheimer's disease, misassembly of the Abeta peptide is genetically
linked to proteotoxicity associated with disease etiology. A reduction
in Abeta proteotoxicity is accomplished, in part, by the previously
reported Abeta disaggregation and proteolysis activities-under partial
control of heat shock factor 1, a transcription factor regulating
proteostasis in the cytosol and negatively regulated by insulin growth
factor signaling. Herein, we report an improved in vitro assay to
quantify recombinant fibrillar Abeta disaggregation kinetics
accomplished by the exogenous application of C.elegans extracts. With
this assay we demonstrate that the Abeta disaggregation and
proteolysis activities of C.elegans are separable. The disaggregation
activity found in C.elegans preparations is more heat resistant than
the proteolytic activity. Abeta disaggregation in the absence of
proteolysis was found to be a reversible process. Future discovery of
the molecular basis of the disaggregation and proteolysis activities
offers the promise of delaying the age-onset proteotoxicity that leads
to neurodegeneration in a spectrum of maladies.
PMID: 19701939
I hate excess proteotoxicity. Doesn't it screw with NAD and the ER?
Cr (caloric restriction) will suPPress proteotoxicity. So try
resveratrol for that as well?
Swell idea----> me...:)~
www.ncbi.nlm.nih.gov/pubmed/19372390
Proteasomal regulation of the hypoxic response modulates aging in C.
elegans.
Mehta R, Steinkraus KA, Sutphin GL, Ramos FJ, Shamieh LS, Huh A, Davis
C, Chandler-Brown D, Kaeberlein M.
Department of Pathology, University of Washington, Seattle, WA 98195,
USA.
The Caenorhabditis elegans von Hippel-Lindau tumor suppressor homolog
VHL-1 is a cullin E3 ubiquitin ligase that negatively regulates the
hypoxic response by promoting ubiquitination and degradation of the
hypoxic response transcription factor HIF-1. Here, we report that loss
of VHL-1 significantly increased life span and enhanced resistance to
polyglutamine and beta-amyloid toxicity. Deletion of HIF-1 was
epistatic to VHL-1, indicating that HIF-1 acts downstream of VHL-1 to
modulate aging and proteotoxicity. VHL-1 and HIF-1 control longevity
by a mechanism distinct from both dietary restriction and insulin-like
signaling. These findings define VHL-1 and the hypoxic response as an
alternative longevity and protein homeostasis pathway.
PMID: 19372390
Back to Bob Dillin and dietary restriction. Which is CR btw.
Dillin and worm FOOD for fodder or ruminations?
www.ncbi.nlm.nih.gov/pubmed/19553937
Nature. 2009 Jul 16;460(7253):396-9. Epub 2009 Jun 24.
A conserved ubiquitination pathway determines longevity in response to
diet restriction.
Carrano AC, Liu Z, Dillin A, Hunter T.
Molecular and Cell Biology Laboratory, The Salk Institute for
Biological Studies, La Jolla, California 92037, USA.
Dietary restriction extends longevity in diverse species, suggesting
that there is a conserved mechanism for nutrient regulation and
prosurvival responses. Here we show a role for the HECT (homologous to
E6AP carboxy terminus) E3 ubiquitin ligase WWP-1 as a positive
regulator of lifespan in Caenorhabditis elegans in response to dietary
restriction. We find that overexpression of wwp-1 in worms extends
lifespan by up to 20% under conditions of ad libitum feeding. This
extension is dependent on the FOXA transcription factor pha-4, and
independent of the FOXO transcription factor daf-16. Reduction of
wwp-1 completely suppresses the extended longevity of diet-restricted
animals. However, the loss of wwp-1 does not affect the long lifespan
of animals with compromised mitochondrial function or reduced insulin/
IGF-1 signalling. Overexpression of a mutant form of WWP-1 lacking
catalytic activity suppresses the increased lifespan of diet-
restricted animals, indicating that WWP-1 ubiquitin ligase activity is
essential for longevity. Furthermore, we find that the E2 ubiquitin
conjugating enzyme, UBC-18, is essential and specific for diet-
restriction-induced longevity. UBC-18 interacts with WWP-1 and is
required for the ubiquitin ligase activity of WWP-1 and the extended
longevity of worms overexpressing wwp-1. Taken together, our results
indicate that WWP-1 and UBC-18 function to ubiquitinate substrates
that regulate diet-restriction-induced longevity.
PMID: 19553937
There are eight hits for dillin + igf-1 and 17 returns for keywords:
igf-1 + resveratrol
Doesn't it all come down to feast or famine and ability to detox in
times of good and plenty?
www.ncbi.nlm.nih.gov/pubmed/18850202
35 returns- keywords: igf-1 + psoria*
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=igf-1+psoria*&log$=activity
===============
Certainly the one thing for sure is agonism and VDR?
www.ncbi.nlm.nih.gov/pubmed/19500727
J Steroid Biochem Mol Biol. 2009 Jul;115(3-5):91-7. Epub 2009 Mar 31.
Premature aging in vitamin D receptor mutant mice.
Keisala T, Minasyan A, Lou YR, Zou J, Kalueff AV, Pyykkö I, Tuohimaa
P.
Department of Anatomy, Medical School, University of Tampere, Tampere
33014, Finland. tiina....@uta.fi
Hypervitaminosis vitamin D(3) has been recently implicated in
premature aging through the regulation of 1alpha hydroxylase
expression by klotho and fibroblast growth factor-23 (Fgf-23). Here we
examined whether the lack of hormonal function of vitamin D(3) in mice
is linked to aging phenomena. For this, we used vitamin D(3) receptor
(VDR) "Tokyo" knockout (KO) mice (fed with a special rescue diet) and
analyzed their growth, skin and cerebellar morphology, as well as
overall motor performance. We also studied the expression of aging-
related genes, such as Fgf-23, nuclear factor kappaB (NF-kappaB), p53,
insulin like growth factor 1 (IGF1) and IGF1 receptor (IGF1R), in
liver, as well as klotho in liver, kidney and prostate tissues.
Overall, VDR KO mice showed several aging related phenotypes,
including poorer survival, early alopecia, thickened skin, enlarged
sebaceous glands and development of epidermal cysts. There was no
difference either in the structure of cerebellum or in the number of
Purkinje cells. Unlike the wildtype controls, VDR KO mice lose their
ability to swim after 6 months of age. Expression of all the genes was
lower in old VDR KO mice, but only NF-kappaB, Fgf-23, p53 and IGF1R
were significantly lower. Since the phenotype of aged VDR knockout
mice is similar to mouse models with hypervitaminosis D(3), our study
suggests that VDR genetic ablation promotes premature aging in mice,
and that vitamin D(3) homeostasis regulates physiological aging.
PMID: 19500727
www.ncbi.nlm.nih.gov/pubmed/19444937
==========
Back to anti-PSORIATIC and anti cancer pathways....?
www.ncbi.nlm.nih.gov/pubmed/17376430
Eur J Pharmacol. 2007 May 7;562(1-2):1-11. Epub 2007 Feb 3.
ATP non-competitive IGF-1 receptor kinase inhibitors as lead anti-
neoplastic and anti-papilloma agents.
Steiner L, Blum G, Friedmann Y, Levitzki A.
Unit of Cellular Signaling, Department of Biological Chemistry, The
Alexander Silberman Institute of Life Sciences, The Hebrew University
of Jerusalem, Jerusalem 91904, Israel.
The insulin-like growth factor-1 receptor (IGF-1 receptor) is a
receptor tyrosine kinase, highly homologous to the insulin receptor.
In contrast to the insulin receptor, which is mostly involved in
metabolic pathways, the IGF-1 system plays a pivotal role in normal
and neoplastic cell growth through anti-apoptotic, proliferative and
metastatic pathways. Furthermore, IGF-1 receptor over-activation is
found to correlate with a variety of tumors, such as breast cancer,
prostate cancer, hematological malignancies, colorectal cancer and
other proliferative diseases, such as psoriasis and papilloma. In
addition, accumulating evidence implies that blockade of IGF-1
receptor activity causes reversal of tumor progression in cell lines
as well as in animal tumor models. Because of the central role the
IGF-1 receptor plays in oncogenic maintenance and metastatic
processes, it is a highly appropriate target for anti-cancer agents.
Here we report on a novel substrate-mimic family of IGF-1 receptor
inhibitors. These compounds are tertiary aromatic amines, non-
competitive with ATP and possess high affinity towards the IGF-1
receptor. The most potent compound, SBL02 inhibited the IGF-1 receptor
with an IC(50) of 170 nM in a cell-free kinase assay and was found to
inhibit IGF-1 receptor auto-phosphorylation and substrate
phosphorylation at the low micromolar range in cellular assays. SBL02
also blocks the formation of colonies in soft agar by cancer cells and
inhibits the growth of keratinocytes and of HPV16 immortalized
keratinocytes. This new family of non-ATP competitive, IGF-1 receptor
inhibitors can serve as a lead for the development of anti-cancer,
_____anti-psoriatic____ and anti-papilloma agents.
PMID: 17376430
OK, so where is the problem if there is ONE?
Vitamin D3?
According to a December 3, 2009 article in HealthDay Daily News,
"Vitamin D May Be Tied to Heart Disease Via Genes," if you have a
specific gene variant that reduces vitamin D activation in the body
and high blood pressure, according to a new study, you were found to
be twice as likely as those without the variant to have congestive
heart failure as well as the high blood pressure, the study found.
[ study link: http://news.yahoo.com/s/hsn/20091204/hl_hsn/vitamindmaybetiedtoheartdiseaseviagenes
]
Also see the Dec 3, 2009 UPI article: Heart failure linked to vitamin
D gene, (U.S. researchers linked congestive heart failure to a gene
variant affecting vitamin D activation.) What does this study mean for
consumers of vitamin supplements?
The purpose of the study is to hopefully identify people at increased
risk for heart disease, according to Robert U. Simpson, an assistant
professor of pharmacology at the University of Michigan Medical School
and his research colleagues, as reported by HealthDay Daily News.
The University of Michigan Medical School researchers analyzed the
genetic profiles of 617 people. One-third had hypertension, one-third
had hypertension and congestive heart failure, and the remaining third
served as healthy controls.
Scientists found that a variant in the CYP27B1 gene was associated
with congestive heart failure in people with hypertension. The study
is in the November 2009 issue of Pharmacogenomics.
Previous research showed that mutations that inactivate the gene
reduce the conversion of vitamin D into an active hormone. "This study
is the first indication of a genetic link between vitamin D action and
heart disease," Simpson noted in a news release from the University of
Michigan.
"If subsequent studies confirm this finding and demonstrate a
mechanism, this means that, in the future, we may be able to screen
earlier for those most vulnerable and slow the progress of the
disease," he added.
When consumers examine this study, the main question arises as to
whether someone with the gene mutation should or should not take
supplements of vitamin D. For example, would the vitamin D from
vitamin pills quicken the path towards congestive heart failure in a
person with high blood pressure and the gene mutation, or would extra
vitamin D be beneficial and slow down the decline?
Does the gene variant that inactivates the gene prevent vitamin D from
dietary sources from being converted into an active hormone? Or is
more vitamin D needed? Does the gene mutation cause vitamin D to
calcify the aorta or not? What should persons with the gene mutation
and high blood pressure eat--more or less vitamin D either in
supplements or dietary means? That's the question consumers would like
to know when they read the study. The natural form of vitamin D is
vitamin D3.
What are the risks of taking vitamin D supplements? Do you have that
specific gene mutation?
Do you have the gene mutation? Did anyone in your family have it?
Could you find out whether you've inherited that specific gene
mutation? What are some of the risks of taking too much vitaminD?
Where can you go to find out whether you have the gene mutation,
assuming you also have high blood pressure and a family history of
hypertension and congestive heart failure. Those are health questions
consumers would like to have answered.
Researchers at Johns Hopkins are reporting what is believed to be the
first conclusive evidence in men that the long-term ill effects of
vitamin D deficiency are amplified by lower levels of the key sex
hormone estrogen, but not testosterone, according to a Nov.17th, 2009
news article, "Effects Of Vitamin D Deficiency Amplified By Shortage
Of Estrogen."
(full text below: http://www.medicalnewstoday.com/articles/171130.php
]
In a recent national study of men presented on Nov. 15 at the American
Heart Association's (AHA) annual Scientific Sessions in Orlando, FL,
researchers reported that the new findings build on previous studies
showing that deficiencies in vitamin D and low levels of estrogen,
found naturally in differing amounts in men and women, were
independent risk factors for hardened, narrowed arteries and weakened
bones.
What does vitamin D actually do? It plays an important role in calcium
balance so you get normal bone strength. The major function of vitamin
D is to improve the efficiency of calcium absorption from the small
intestine, according to Dr. Ray Sahelian's newsletter and nutrition
information sites. Can taking too much vitamin D calcify your aorta?
What are the risks? And do you have to inherit a specific gene
variation for vitamin D to calify your coronary arteries? What does
the research show?
What happens to the way your body handles, absorbs, or builds up
vitamin D after menopause when the estrogen level plummets? And were
you born with or without the gene variation that takes the vitamin D3
you eat along with the calcium and calcifies your arteries with it
instead of putting it into your bones where it belongs? How do you
find a genetics/DNA test to tell you whether you have inherited that
genetic mutation or variation?
Epidemiological data show low levels of vitamin D lead to a higher
incidence of breast cancer, colon cancer, prostate cancer, ovarian
cancer, as well as multiple myeloma, according to Dr.Sahelian's site.
Patients with Crohn's disease are known to have low levels. Vitamin D
supplementation may even improve mood during the winter months,
according to Dr. Sahelian. But you'd be better off taking less than
more until you know how much you'll really need of vitamin D.
Scientists repeatedly warn vitamin consumers of the danger regarding
excessive intake. Vitamin D taken in high amounts can cause excessive
calcification of bone, calcification of soft tissue, kidney stones,
headaches, weakness, nausea, and vomiting.
There answer right now is that no one knows exactly the long-term
effects of high dose daily use of vitamin D. Find out whether or not
you need to supplement at all. Research is ongoing. In the meantime,
are you taking a teaspoon full of cod liver oil that already has 400
units of vitamin D in it along with some vitamin A? Look at the label
and see whether it tell you the vitamin content of the oil. How do you
compare the different answers given by your various heathcare
professionals?
When you take all those vitamin D3 supplements that are recommended in
so many articles in the media, how do you know whether your body will
use it to protect your organs against bone loss or use it to send
calcium deposits into your organs, heart valves, and arteries?
Find out from your doctor whether or not your blood test tell you that
you may or may not need to supplement. Does your diet have plenty of
vitamin D? Do you get enough sun exposure?
Most people may benefit from taking 400 units a day either as part of
a multivitamin product and a balanced diet. A few people without much
sun exposure and a poorer diet, or if you live in latitudes where
there's not much sun, might benefit from 600-800 units of vitamin D3.
The only questions scientists have is that over a long term, we don't
know what the risks are. You're doctor should talk with you if you
have chronic medical conditions whether you need up to 1,000 units
daily. But the question is for how long without posing a risk of
calcifying your arteries from too high a dose for too long a time of
taking supplements of vitamin D.
When you do take a supplement, be sure it's natural vitamin D3, not
synthetic vitamin D2. The conclusion is the final word is not yet in
on the danger of calcifying your brain and arteries with too much
vitamin D supplementation.
Why take the risk when you can keep your supplementation, if any, to a
dose related to what your body needs. You can find out what vitamin
deficiencies you have by taking a test to see what's actually absorbed
into your cells and what's just floating in your bloodstream.
What needs to be evaluated right now is whether other genes that
control calcium homeostasis are involved in the pathogenesis of this
disorder. In plain language, how many gene variations control the way
calcium and vitamin D3 are processed in your own body? And how can you
find out? Are there genetic tests that show you how your body handles
vitamin D3?
The media is full of articles saying that the 400 mg of vitamin D3 is
too little to protect you against cardiovascular problems, that you
probably need 1,000 mg. But what happens if you have a genetic
variation or mutation that communicates to your body in a different
way, where when you take vitamin D3 and calcium in supplements or at
high food intakes, that the calcium doesn’t go into your bones, but
into the arteries and valves around your heart? Will vitamin K2 in the
MK-7 form protect you from calcification if you have this genetic
variation? And where can you find out if it will? All these answers
require scientific studies, namely, research.
Another article at BioMed Experts, Osteoporosis and calcification of
the aorta, Bone and Mineral, 1992;19(2):185-94,1992: Frye M A; Melton
L J; Bryant S C; Fitzpatrick L A; Wahner H W; Schwartz R S; Riggs B L,
notes, “Aortic calcification was not associated with any measures of
calcium metabolism, after adjusting for age, except for a slight
negative association between linear aortic calcifications and 25(OH)
vitamin D levels (P < 0.05).”
Another abstract of a 2003 article, "Influence of sex and estrogen on
vitamin D-induced arterial calcification in rats" notes, "It is known
that the process of arteriosclerosis is affected by sex and estrogen.
The present study was thus undertaken to examine the effects of these
factors on arterial calcification, a form of arteriosclerosis, using a
rat model of vitamin D toxicity.
The article concludes with, “These results suggest that sex and
estrogen can modify the process of arterial calcification. The
mechanisms remain to be determined, although the effects were
independent of serum calcium level.”
Will taking vitamin K2 in the MK-7 form help you if you have this gene
variation whereby taking too much vitamin D starts to calcify your
aorta? Or not? Only science can tell you for sure, and the science
needs to be tailored to your individual genes. Is science ready yet?
Have they developed a test? Or does science still not know yet how
many genes need to be tested to see how your body handles vitamin D3
and calcium?
You hear all the talk about increasing your daily natural vitamin D3
intake from 400 mg to at least 1,000 mg to prevent arterial
calcification, bone loss, and certain diseases. The media says so many
diseases could be due to too low vitamin D3 intake. But what happens
if you have a certain gene variation that instead causes vitamin D3 to
calcify your aortic valves?
There is some early research that high amounts of vitamin D, such as
2,000 iu, taken daily for many months or years may lead to
calcification of arteries, according to Dr. Ray Sahelian's newsletter.
How do you know what to take?
Until more studies are published we prefer to be cautious and have
people only take one or two vitamin D 400 iu a day. Some doctors are
recommending daily dosages of 1000 units or higher. Research in
medical journals report that many people in this country are not
getting enough of this vitamin. But what is the right dosage for
supplementation so you don't calcify the arteries in your brain or
heart?
If you have a gene variation, does vitamin D cause calcification of
your aorta? See the article at the CAT. Inst. site. Another article in
the Journal of Vascular Research, Aortic Calcification Produced by
Vitamin D3 plus Nicotine, notes that “Calcification of the elastic
arteries of the young rat by treatment with vitamin D and nicotine
(VDN) has been proposed as an animal model of arterial calcification
associated with age and age-related vascular pathology in man.
The calcium-binding protein, S-100, which is found in human
atherosclerotic lesions was associated with medial calcification of
the aorta in VDN rats, especially in cases of severe calcification.”
The abstract’s conclusion is that, “In conclusion, the mechanisms and
consequences of aortic calcification in VDN show several similarities
with calcification occurring in human athero- and arteriosclerosis.”
See the conclusion of the article in the MD Consult Preview, The
vitamin D receptor genotype predisposes to the development of calcific
aortic valve stenosis. - Ortlepp JR - Heart - 01-JUN-2001; 85(6):
635-8 (MEDLINE is the source for the citation and abstract of this
record) that notes, “There is a significant association of vitamin D
receptor polymorphism with calcific aortic valve stenosis. The B
allele of the vitamin D receptor is more common in patients with
calcific aortic valve stenosis. It now needs to be evaluated whether
other genes that control calcium homeostasis are involved in the
pathogenesis of this disorder.”
See the article, at: Oxford Journals, Cardiovascular Research, titled,
Uraemic hyperparathyroidism causes a reversible inflammatory process
of aortic valve calcification in rats. Uraemic hyperparathyroidism
causes a reversible inflammatory process of aortic valve calcification
in rats Renal failure is associated with aortic valve calcification
(AVC). Our aim was to develop an animal model for exploring the
pathophysiology and reversibility of AVC, utilizing rats with diet-
induced kidney disease.
See the publication, Heart, and Education in Heart, a peer review
journal for health professionals in all areas of cardiology. The
article, Cardiovascular medicine, “The vitamin D receptor genotype
predisposes to the development of calcific aortic valve stenosis”, J R
Ortlepp, R Hoffmann, F Ohme, J Lauscher, F Bleckmann, P Hanrath, tests
the hypothesis that vitamin D receptor polymorphism is associated with
calcific aortic valve stenosis. The conclusion noted, “There is a
significant association of vitamin D receptor polymorphism with
calcific aortic valve stenosis. The B allele of the vitamin D receptor
is more common in patients with calcific aortic valve stenosis. It now
needs to be evaluated whether other genes that control calcium
homeostasis are involved in the pathogenesis of this disorder.”
What this means is if you have a genetic variation, a polymorphism on
your vitamin D receptor, it’s association with calcification of your
aortic valve. How do you know whether you have this particular gene
variation that makes your body react a certain way to vitamin D3 by
developing calcium deposits in your aortic valve?
What should you do? Keep asking whether the test is ready yet. And
keep searching to find out whether science has found all the genes
necessary to tell you how your body handles vitamin D3 supplements
versus natural food intake, calcium, magnesium, and fish oils
containing vitamin D3. Until you know, eat whole foods, get enough
sunshine or other natural light, and keep researching.
Find out whether you have the B allele of the vitamin D receptor.
Science knows those with it, at least in rats and some human patients,
it is more common to see calcification of the aortic valve. But
because it is more common, how does that tell us whether the gene
variation is a risk? Or how many genes or alleles are involved? That's
why you have to keep asking those experts that are talking about
health care with you.
Also, on the subject of food cravings, according to the article,
“Combat Your Food Cravings,” in the June 2009 issue of Natural
Solutions magazine, page 79, if you crave sweets, what your body
really needs are trace amounts of chromium, carbon, phosphorus,
sulfur, and tryptophan. You can get all of these in small amounts from
the following foods: To get enough chromium, eat broccoli, grapes,
cheese, dried beans, and chicken. Think about this.
How can you find out whether this idea has been validated in credible
medical journals? Where can you turn to for nutrition information
after reading interviews in magazines?
The only problem with articles where health professionals are
intereviewed is where can you go to validate all these statements in
scientific studies or journals if references aren't listed in a
sidebar? Where can you find the resources without having to subscribe
to the medical journals? Start with the public library or some of the
online nutrition sites that have references.
Resources
Effects Of Vitamin D Deficiency Amplified By Shortage Of Estrogen
17 November 2009 - Researchers at Johns Hopkins are reporting what is
believed to be the first conclusive evidence in men that the long-term
ill effects of vitamin D deficiency are amplified by lower levels of
the key sex hormone estrogen, but not testosterone.
<sniP>
--------------
This link (above)
http://news.yahoo.com/s/hsn/20091204/hl_hsn/vitamindmaybetiedtoheartdiseaseviagenes
(whole text below) Brings up cyp27b1 + genetics in regards to heart
attacks.
As to immunity it takes us back to Gallo and LL37 (LL-37) and
autoimmunity (psoriasis):
7 returns for keywords: psoria* + CYP27B1 [pubmed]
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=psoria*+AND+CYP27B1&log$=activity
It's been my contention, regardless if Susan thinks/knows that the
Marshall Protocols are nonsense, the VDR is still NOT CLEAR for
psoriasis and autoimmunity.
Hence the first of those SEVEN [psoria* + CYP27B1 - pubmed abstracts]
www.ncbi.nlm.nih.gov/pubmed/19720207
J Allergy Clin Immunol. 2009 Sep;124(3 Suppl 2):R13-8.
Antimicrobial peptides and the skin immune defense system.
Schauber J, Gallo RL.
Department of Dermatology and Allergology, Ludwig-Maximilians-
University, Munich, Germany.
Our skin is constantly challenged by microbes but is rarely infected.
Cutaneous production of antimicrobial peptides (AMPs) is a primary
system for protection, and expression of some AMPs further increases
in response to microbial invasion. Cathelicidins are unique AMPs that
protect the skin through 2 distinct pathways: (1) direct antimicrobial
activity and (2) initiation of a host response resulting in cytokine
release, inflammation, angiogenesis, and reepithelialization.
Cathelicidin dysfunction emerges as a central factor in the
pathogenesis of several cutaneous diseases, including atopic
dermatitis, in which cathelicidin is suppressed; rosacea, in which
cathelicidin peptides are abnormally processed to forms that induce
inflammation; and psoriasis, in which cathelicidin peptide converts
self-DNA to a potent stimulus in an autoinflammatory cascade. Recent
work identified vitamin D3 as a major factor involved in the
regulation of cathelicidin. Therapies targeting control of
cathelicidin and other AMPs might provide new approaches in the
management of infectious and inflammatory skin diseases.
PMID: 19720207
What do we know from simply using D3 supplements?
Easy..open mouth and insert D3. Then look at psor skin the next
two or so months.
Does it clear up? Are you also standing around naked under the sUN?
This abstract goes back to January of 1993.
www.ncbi.nlm.nih.gov/pubmed/8381921
Ned Tijdschr Geneeskd. 1993 Jan 30;137(5):232-6.
[Vitamin D 3 analogs, e new therapy for psoriasis]
[Article in Dutch]
van de Kerkhof PC, de Jong EM, Arnold WP, de Mare S, Hol CW.
Academisch Ziekenhuis, Afd. Dermatologie, Nijmegen.
PMID: 8381921
------------
So? I bet cave men knew the sun was good for ugly arse skin. LOL
I guess if D3 supplementation worked in 1993 it would work NOW. LOL
CYP27B1 with randall, psoriasis as keywords in the groups: 10 or so
hits
http://groups.google.com/groups/search?hl=en&ie=UTF-8&q=+CYP27B1++randall+psoriasis&btnG=Search&sitesearch=
LOL...
http://en.wikipedia.org/wiki/25-Hydroxyvitamin_D3_1-alpha-hydroxylase
Symbol CYP27B1
25-Hydroxyvitamin D3 1-alpha-hydroxylase is a cytochrome P450 enzyme
in the proximal tubule which converts calcidiol to calcitriol (the
bioactive form of Vitamin D).
YeP just another cyp450 bugaboo?
http://en.wikipedia.org/wiki/Cytochrome_P450
=========
The full story to the above link:
http://news.yahoo.com/s/hsn/20091204/hl_hsn/vitamindmaybetiedtoheartdiseaseviagenes
Vitamin D May Be Tied to Heart Disease Via Genes
THURSDAY, Dec. 3 (HealthDay News) -- New research points to the
possibility of a genetic link between vitamin D and heart disease.
People with high blood pressure who had a gene variant that reduces
vitamin D activation in the body were found to be twice as likely as
those without the variant to have congestive heart failure, the study
found.
The finding may lead to a way to identify people at increased risk for
heart disease, according to Robert U. Simpson, an assistant professor
of pharmacology at the University of Michigan Medical School and his
research colleagues.
They analyzed the genetic profiles of 617 people. One-third had
hypertension, one-third had hypertension and congestive heart failure,
and the remaining third served as healthy controls.
The researchers found that a variant in the CYP27B1 gene was
associated with congestive heart failure in people with hypertension.
The study is in the November issue of Pharmacogenomics.
Previous research showed that mutations that inactivate the gene
reduce the conversion of vitamin D into an active hormone.
"This study is the first indication of a genetic link between vitamin
D action and heart disease," Simpson said in a news release from the
University of Michigan.
"If subsequent studies confirm this finding and demonstrate a
mechanism, this means that, in the future, we may be able to screen
earlier for those most vulnerable and slow the progress of the
disease," he added.
More information
<sniP>
This one goes with the same article
http://www.medicalnewstoday.com/articles/171130.php
Effects Of Vitamin D Deficiency Amplified By Shortage Of Estrogen
Researchers at Johns Hopkins are reporting what is believed to be the
first conclusive evidence in men that the long-term ill effects of
vitamin D deficiency are amplified by lower levels of the key sex
hormone estrogen, but not testosterone.
In a national study in 1010 men, to be presented Nov. 15 at the
American Heart Association's (AHA) annual Scientific Sessions in
Orlando, researchers say the new findings build on previous studies
showing that deficiencies in vitamin D and low levels of estrogen,
found naturally in differing amounts in men and women, were
independent risk factors for hardened and narrowed arteries and
weakened bones. Vitamin D is an essential part to keeping the body
healthy, and can be obtained from fortified foods, such as milk and
cereals, and by exposure to sunlight.
"Our results confirm a long-suspected link and suggest that vitamin D
supplements, which are already prescribed to treat osteoporosis, may
also be useful in preventing heart disease," says lead study
investigator and cardiologist Erin Michos, M.D., M.H.S.
"All three steroid hormones - vitamin D, estrogen and testosterone -
are produced from cholesterol, whose blood levels are known to
influence arterial and bone health," says Michos, an assistant
professor at the Johns Hopkins University School of Medicine and its
Heart and Vascular Institute. "Our study gives us a much better
understanding of how the three work in concert to affect
cardiovascular and bone health."
Michos says the overall biological relationship continues to puzzle
scientists because studies of the long-term effects of adding estrogen
in the form of hormone replacement therapy in women failed to show
fewer deaths from heart disease. Indeed, results showed that in some
women, an actual increase in heart disease and stroke rates occurred,
although, bone fractures declined.
The Hopkins team's latest data were provided by analyzing blood
samples from a subset of men participating in a study on cancer. That
study was part of a larger, ongoing national health survey involving
both men and women and was designed to compare the risk of diseases
between those with the lowest blood levels of vitamin D to those with
higher amounts. An unhealthy deficiency, experts say, is considered
blood levels of 20 nanograms per milliliter or lower.
The men in the study had their hormone levels measured for both
chemical forms of testosterone and estrogen found in blood, when each
is either unattached or circulating freely, and when each is attached
to a separate protein, known as sex hormone binding globulin, or SHBG
for short.
Initial results showed no link between vitamin D deficiency and
depressed blood levels of either hormone. And despite finding a
harmful relationship between depressed testosterone levels and rates
of heart disease, stroke, and high blood pressure, as well as
osteopenia in men, researchers found that it was independent of
deficiencies in vitamin D.
However, when researchers compared ratios of estrogen to SHBG levels,
they found that rates of both diseases, especially osteopenia, the
early stage of osteoporosis, were higher when both estrogen and
vitamin D levels were depressed.
For every single unit decrease in ratios of estrogen to SHBG (both in
nanomoles per liter), men low in vitamin D showed an 89 percent
increase in osteopenia, but men with sufficient vitamin D levels had a
less worrisome 64 percent jump.
Using the same measure of estrogen levels, men low in vitamin D were
also at heightened risk of cardiovascular diseases, at 12 percent,
compared to men with adequate levels of the vitamin, at 1 percent,
numbers that researchers say are still statistically significant.
"These results reinforce the message of how important proper
quantities of vitamin D are to good bone health, and that a man's risk
of developing osteoporosis and heart disease is heavily weighted on
the complex and combined interaction of how any such vitamin deficits
interact with both their sex hormones, in particular, estrogen,"
Michos says.
Michos and her team next plan to analyze blood samples from women to
see if the same results from men hold true.
Michos recommends that men and women boost their vitamin D levels by
eating diets rich in fatty fish, such as cod, sardines and mackerel,
consuming fortified dairy products, taking vitamin supplements, and in
warmer weather briefly exposing skin to the sun's vitamin-D producing
ultraviolet light.
She points out that clinical trials are under way to determine whether
or not vitamin D supplements can prevent incidents of or deaths from
heart attack, stroke and other signs of cardiovascular disease.
The U.S. Institute of Medicine suggests that an adequate daily intake
of vitamin D is between 200 and 400 international units, but Michos
feels this is inadequate to achieve optimal nutrient blood levels
(above 30 nanograms per milliliter). Previous results from the same
nationwide survey showed that 41 percent of men and 53 percent of
women are technically deficient in the nutrient, with vitamin D levels
below 28 nanograms per milliliter.
Funding for this study was provided by the Hormone Demonstration
Project, a part of the Maryland Cigarette Restitution Fund Research
Grant Program at the Johns Hopkins University. Additional support was
provided by the American College of Cardiology Foundation and a
Clinician Scientist Award at the Johns Hopkins University.
Besides Michos, other researchers at Johns Hopkins involved in this
study were Jared Reis, Ph.D.; and Meredith Shields and Elizabeth
Platz, Ph.D., Sc.D., at the University's School of Public Health; and
Sabine Rohrmann, now at the German Cancer Research Center in
Heidelberg. Another investigator in this research was Nader Rifai,
Ph.D., at Children's Hospital Boston and Harvard Medical School.
(Presentation title: The association of cardiovascular disease and
osteopenia may be mediated through a vitamin D-sex steroid hormone
interaction, results from the Third National Health and Nutrition
Examination Survey, NHANES-III.)
Source: David March
Johns Hopkins Medical Institutions
=========================
So?
How many times will this snake swallow his OWN tail?
Till the sun don't shine NO doubt.
If only.... we didn't shed it 1000 times faster then the human
RACE....
randall...the Uroborus of Psor life under the SUN-- or another heart
attack..