This Is MS Multiple Sclerosis Knowledge & Support Community

The new insights require a paradigm shift in the medical world.

From this conference programme, we see how the new insights percolate slowly into the system
http://www.slideshare.net/gavingiovanno ... osium-2012

In my view, the programme itself reads as a blue print for the future of MS care.
Broadly speaking, it follows the same reasoning as this thread, i.e., that MS is a two stage disease with an important role for the gut.

The other threads on vitamin D in pregnancy and the effect of the birth-month are related to the subject matter
http://www.thisisms.com/forum/general-d ... 21166.html
http://www.thisisms.com/forum/general-d ... 21172.html

But the researchers have it all mixed up.
Of course, the risk of MS relates to the month of birth.
What is important here is the vitamin D available in the blood stream during the main phases of cellular growth.
The cell composition (and number of vit D gates) is directly related to the vit D available in the blood,
that is of the mother (fetus) and the own blood stream (adolecence).
During the Summer, the vit D concentration will be higher (matter of sun exposure) where cells built will have more vit D gates..

The vitamin D relationship itself is more complex and in the minds of people often convoluted.
This needs to be unravelled.
There is the matter of the cell composition (see above).
Vit D supplementation then is probably affecting the gut flora (and peptides for natural antibiotics).
Further, the vit D metabolism in the blood may in some way be related to the gut concentration
but there is an advanced regulatory loop as well between active and non-active vit D,
and that loop is influenced by disease activity (the reverse path from active to non-active).
In this same context, it is unclear to me whether there is a difference between the own body generated vit D and the administered D; there are indications that there is a difference.. (so we should not block the sun, neither the mother nor the growing child; may explain tthe sharp rise in immune diseases...)

When the Vit D receptor and other receptors are enabled again, 1000 or more genes will be transcribed again,
with effects on the organs, and also the nerves..
And the body will take metabolic control again..

In my case, the bad gut developed already around 1997/98 while I was diagnosed with MS in 2004.
This gives an indication of the time spans involved; it took years to disable the VDR.
when the gut flora is restored, the VDR and other receptors are enabled again, it may take a year or more to re-establish metabolic control and improve nerve condition..

Persistent Chlamydophila Pneumoniae (CPn) Infection In Multiple Sclerosis and Chronic Cerebrospinal Venous Insufficiency (CCSVI)
http://www.cosmeticcentre.com.au/site/i ... lay=329348

MS is presented as the end result of progressive persistent venulitis caused by chronic CPn infection..

I think this is correct, for the first phase.
During this stage, the inflammation of the small blood vessels (capillaries and lymphatic system) by Cpn is explained by a blocking of the VDR by the Cpn...

The information and links on this thread provide a highly consistent and very plausible picture about the relationship of MS with the VDR...

http://www.ncbi.nlm.nih.gov/pubmed/23139386

http://www.thisisms.com/forum/general-d ... 21135.html

I think it works like this:

The iron does not accumulate "in the brain" itself but on the vessel walls of the finest capillaries and in the lymphatic system...
And what happens then is that the functioning of key receptors in the endothelium which have many important functions (cellular feeding, transcription) weakens..
This is happening in the early stages.

A bacterial or virus infection (that block the VDR) on top of that will create such adverse conditions to a point where the immune system signals there is something going wrong. And the immune system corrects..
And you get RR.

The second (progressive) phase for MS is caused by a different mechanism altogether.
It comes up from the gut..

The very first posting of this thread (on pg 1) explains the cascade of events in more detail...

As we have seen, MS is a disease in two stages.

The second phase in MS comes up from the gut and causes a faulty brain bowel connection.

I think it starts with a bad gut and ultra bad cholesterol and badly trained T/B cells proliferating through the body. This causes a distorted autonomic nervous system.

The autonomic nervous system has two divisions, sympathetic and parasympathetic. The sympathetic prepares the body for action increasing metabolic functions such as heart rate and blood pressure. The parasympathetic system works in a somewhat opposite manner stimulating the rest and repair functions such as digestion and urination.

An abnormal functioning of the parasympathetic system then may cause problems with the bladder and other organs including a poor gut peristalsis and functioning, altered sweating, heat intolerance etc. We may recognise the symptoms.. see e.g.
http://www.synergyhealthconcepts.com/symptoms/ and
http://blog.synergyhealthconcepts.com/w ... stract.pdf
with the side note that the ccsvi is just one factor causing the troubled parasymphathetic system..

To summarise: I am sure it is all connected as the figure in the article under the first link above suggests. But the direction of causality is more complicated. In fact, I think the intestine is involved in two ways: in first as the root cause of the abnormal functioning of the parasympathetic system and then in a second stage it may suffer from the consequences of an abnormal functioning of the parasympathetic system and lack of peristalsis. A circular loop is thus established that reinforces itself... whow I see it now, and then you get MS...

If you want to break the loop, I think it starts with normalising the gut flora..

when only the metabolism can master the complexity

For some time now I take common diabetes type 2 medication. The relationship of MS with diabetes and the important role of the gut have been explored on this thread and look very likely and plausible.

My feces has improved, strongly improved; the gut peralstesis is starting to improve as well. I think the latter involves the loop via the parasympathetic nervous system. And will further help improve the overall gut functioning. But the motor functions have not really improved, or perhaps I should say have not yet… I keep the fingers crossed..

But besides the improved gut functioning, there are other symptoms that would suggest that there are things happening inside the metabolism, good things… And that the metabolism is trying to restore to normal conditions…

A few weeks ago, this message was in a Belgian newspaper: The mystery of morning erection explained. The source is the Huffington Post. http://www.huffingtonpost.com/2012/11/1 ... 38103.html The article in the Belgian newspaper reads as follows (translated from Dutch):

"Each man suffers from it since his adolescence: to wake up with an erection. Although this gives difficult moments to pee and can provide embarrassing situations, experts argue that this phenomenon benefits for the body.

A morning erection is a part of the normal sleep cycle and occurs several times a night. The brain undergoes various stages of sleep every night: that goes from superficial non-REM sleep to deep sleep. This cycle repeats on average four times per night. During the REM stage you dream, but there are also physical changes.

Your brain then blocks neurotransmitters, to prevent your dreams will actually perform. One of these substances is norepinephrine, which is also involved in the control of erections. During REM sleep the level thereof decreases, causing the blood vessels to dilate, and therefore some more blood going into the arteries with an erection as a consequence.

This is an important process in the body, since this provides additional oxygen in the blood, causing damage to cells helping to be restored. Because we often wake up during the REM stage, so are the chances that a man wakes up with an erection."

Now you may think this is all a bit far-fetched. But this phenomenon did not happen to me for the last say 15 years. But over the last several months, this has become almost like normal. I think that there are things happening inside my body that are immersed in the immense complexity of our micro-cosmos, a complexity that only the metabolism itself can handle... where it all relates together in some way and starts to work again as a metabolism taking metabolic control .…

I also think that it is precisely these sort of things that are important for general vascular health and – I hope – in good time for the recovery from MS. Because general vascular health improves, because the endothelium even in the finest capillaries and lymphatic system improves, receptor functioning will improves, nutritional and transcription processes will strenghten and…

In the last posting, we have seen how the metabolism itself may be dealing with the huge complexity. But perhaps there is also a role, an important role, for the Internet.

The Internet has been earmarked as "the most powerful infrastructure ever known for the creation, exchange and implementation of ideas". "It empowers the individual, and it empowers individuals who wish to work together." It is now such "a vibrant source of innovation" put "at the centre of driving economic growth and renewal."
http://papers.ssrn.com/sol3/papers.cfm? ... id=2104350

The Internet is central to facilitate individuals and groups in health matters e.g. for HIV. Which motivates the broad communities to align behind a call to action. For instance, improvements in HIV treatment began when well-organized patient groups started collaborations with other stakeholders. Patient engagement has helped improve outcomes for people with HIV.
http://link.springer.com/article/10.100 ... 012-6656-6

“Patients Like Me” is a networking site that was established to collect data directly from individuals with similar ailments. Individuals put their own individual symptom-related data into the network and also record any medicines or supplements they are taking, the doses, their reactions, and other pertinent medical information. The groups are testing the results of various medicines and dosages through the internet in patient self-organized clinical trials that would not be officially available through government, drug company, or lab-sponsored trials for years. This experiment is the real-world application of the theoretical construct that market economics can be overcome by social production.
Francis Bator, the author of the Book The Anatomy of Market Failure (MIT Press), said already in 1958: “Efficient markets may not do [give innovation beneficial to the extent that it enhances public values and equitable and positive social outcomes], efficiency of the ‘invisible hand’ does not preclude preference for other efficient modes of organization”.

The experiment is opening up research that heretofore has been kept secret. Such patient-to-patient exchanges of information change the very nature of intellectual property and knowledge ownership in the health care field. Disruptive innovations enabled by ICT often rely on common ownership of knowledge. The health care field provides numerous examples of how ICT is changing the balance of power and expertise due to increasing access to knowledge. Advances in ICT, combined with advances in genomics, molecular diagnostics, and micro-fluidics, are driving a shift in health care away from a centralized model that puts the physician at its core to a more decentralized approach centered on the patient.
http://pressoffice.telefonica.com/docum ... Ingles.pdf

This course challenges companies' interest in protecting proprietary data in which they have invested significant time and money that works against “sharing for free.” It challenges university researchers who may want to preserve ownership of their knowledge to get tenured teaching spots or to advance their reputations and governments that have public safety-related responsibilities with stringent efficacy standards to maintain. The barriers have been described in a beautiful way in

But the fundamental challenge, also for governments, for any investigative field where entrenched hypotheses dominate is to ensure that novel avenues of investigation remain open and productive. Open access to knowledge and entering into new ways of doing things may lead to gains that cannot be measured in raw economic terms. In the health domain for instance, it will lead to greater patient-doctor communication, empowering patients to take a more active role in the management of their disease than has historically been possible. Clearly with risks attached to it but also with potentially great reward…

Just like for HIV, I am sure that is true for MS too. I think we only need to find the right modus operandi for an "MS patients like me" as the next big step in this continuing saga.

This video brings it all together http://www.kriskris.com/the-bitter-truth-about-sugar/
whow, it is really good, I looked at it twice and will look at it again..
Obesitas, vit D, diabetes2, insulin (resistance), inflammation, LDL cholesterol, triglycerin, ..

I think it is the metabolic balance that is lost in MS.
Insulin is one part of the broader picture..
Proper gut functioning is central to restore health...

..........

Dear Leonard,

You have such a wonderful way of thinking and lots of informations too. Pardon me, but i feel lost reading your posts coz it's a heavy stuff for me to read. But i wonder what is your conclusion of your hypothesis? What is the first culprit that started MS to develop from your hypothesis?

Maybe you're so closed in gathering all pieces of this puzzle.

Thank you.

Dear Leonard,
I thought Diabetes caused blood circulation problems. Why complicate things beyond that? Just one among many causes of CCSVI blood circulation problems. Obviously if one has Diabetes it should be addressed and that alone may be the solution for some.

MS Cure Enigmas.net

MS is a subtle multi-facetted metabolic disease, of a metabolism that lost control. I am sure it involves many pathways, some with rather long time-constants (measured more in years than in months). Neuro-inflammation is considered secondary and consequential, the multiple sclerosis are likewise. Inflammation is caused by impaired cellular nutrition; improved cellular nutrition calms down the (re-active) immune system. Endothelial damage (e.g. ccsvi) is considered a factor that weakens nutritional conditions and instigates inflammation, and it breaks the tissue of the BBB.

One pathway that controls the metabolism is the Fibroblast Growth Factor – 21 (FGF21), the Lean Body Hormone. I am not saying that it is the only but certainly a candidate to be studied further because it brings it all together, because it fits the broader picture that emerges from this thread so neatly. See the other thread on TIMS on the subject: Check this out!!!
http://www.thisisms.com/forum/general-d ... 21659.html

The FGF21 hormone requires the Klotho protein to function; Klotho is needed for FGF21 activation. Vit D increases the Klotho protein. Vit D and FGF21 work in tandem. More functional FGF21 thus would seem to require more Klotho, and more Vit D. The direction of causality is not entirely clear to me, perhaps it is the interaction that makes this a functional complex… http://lewrockwell.com/sardi/sardi245.html

What is of great interest here is that the FGF/Klotho seems to have a direct path to the myelin biology, both for protecting brain myelin and for promoting repair! In fact, significant effects were found of Klotho on oligodendrocytes function including maturation of OPCs in vitro and myelination. Where perhaps a deficient metabolic pathway would cause some let's say "collateral damage" to our myelin. Wow..
http://www.jneurosci.org/content/33/5/1927.abstract
http://www.medicalnewstoday.com/releases/255694.php

The resemblance of the FGF biological action and diabetes 2 (which is also a nutritional issue) is striking. FGF22/Klotho increases through physical exercise (is known as the best therapy for diabetes2), it increases through fasting and starvation (weight loss is also a best therapy for diabetes2), while inflammation decreases FGF21/Klotho (and thus leads to further myelin damage?).

If we consider possible therapeutic options, it becomes even more interesting:

- the Vit D: we know about the potential beneficial effects of Vit D for MS, it has been widely reported;

- and Metformin (we know from diabetes2 and from this thead): reduces blood sugar, arguably it would stimulate FGF21 in human liver cells! Here one could even think of synergetic effects of Vit D (Klotho production) and Metformin (FGF21 production)… The working mechanism of Metformin is unknown. Is it the FGF21 production?

- and IP6 or Inositol Hexaphosphate (equivalent to a low phosphate diet provided in plant foods; in contrast, inorganic phosphorus is prevalent in fast foods) : is this where the secret of the Walsh diet lies?

The metabolism is highly complex, the direction of causality is often unclear, vicious circles and interaction may complicate matters further. I think the acronym MS stands more for Metabolic Syndrome than for Multiple Sclerosis which I consider an effect on the fringes. Where the key for our problem lies somewhere in the endocrinological space between:

- GLUT functioning, high RBC ATP for MS, low RBC ATP for diabetics;
- the VDR and its heterodyme connection to the RXR and transcription activity;
- FGF21 hormone/Klotho protein/Vit D complex.

I think we need a new all-encompassing theory on cellular nutrition and inflammation. And possibly we need a critical look at food safety and the food pyramid.

Hi Leonard,
I was wondering how these stress-related studies fall into your theory. Stress, via stimulation of raas, can negatively impact klotho production which can result in vitamin d deficiency. Inversely, vitamin d increases klotho by reducing raas activity. Your response on the stress thread made me wonder but I thought I'd ask here so you could keep a cohesive line of thinking in one spot.

Brain Angiotensin II, an Important Stress Hormone: Regulatory Sites and Therapeutic Opportunities
http://onlinelibrary.wiley.com/doi/10.1 ... edMessage=

http://www.thisisms.com/forum/post20393 ... 23#p203931

I'm working on the theory that things don't have to be that complicated to be complicated. Do we really need to blame multiple causes if one irregularity can cause so much fallout? Just a theory. . I'm interested in your thoughts on the stress-raas-klotho-everything else implications in MS.

Anonymoose wrote:I'm working on the theory that things don't have to be that complicated to be complicated. Do we really need to blame multiple causes if one irregularity can cause so much fallout? Just a theory. . I'm interested in your thoughts on the stress-raas-klotho-everything else implications in MS.

There's just one little problem called confounding factors,
Everytime you try to isolate one factor you will find exceptions to the rule and I have no doubt that if you investigated the stress line you would find the same problem.

This is most likely one of the problems with the state of science currently in the degree of specialisation, many individuals doing work on MS in specific areas, but very few looking at how all this info ties into the big picture.

There are millions of people on the planet who have the genetic predisposition to developing MS or another chronic disease, yet only a small proportion of them ever develop the disease.

Everything I've looked at suggests that they are all multifactorial and stress does form a part of the problem, but stress alone is a dead end street.

I just look at it like the "Siege Scenario" the body is under constant attack, we must remind ourselves that life itself is fighting the laws of nature which is chaos, so the body is constantly trying to maintain structure in the face of the environment which is trying to dismantle this structure. Overall the human model has a design life of around 120 years in a best case scenario, and there are a number of factors which reduce this, major trauma, genetics, corrosive environmental exposure and poor maintenance. We can ignore the first one in this discussion because sometimes there is an accident and people die.

The others cover predisposition, environmental factors, toxins, diet, exercise, lifestyle, stress and psychological behaviours improvements in any or all of these areas reduce the risk of the predisposition developing into the disease.

Anonymoose wrote:Hi Leonard,
I was wondering how these stress-related studies fall into your theory. Stress, via stimulation of raas, can negatively impact klotho production which can result in vitamin d deficiency. Inversely, vitamin d increases klotho by reducing raas activity. Your response on the stress thread made me wonder but I thought I'd ask here so you could keep a cohesive line of thinking in one spot.