A new concept and treatment options for MS

If it's on your mind and it has to do with multiple sclerosis in any way, post it here.

Postby jimmylegs » Tue May 03, 2011 2:41 pm

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Postby Leonard » Tue May 10, 2011 1:07 am

I think the debate is one of pro-nutrition versus anti-inflammation. What do I mean with this?

Take the following example: Metformin (common anti-diabetics drug) activates AMPK (an enzyme that plays a role in cellular energy homeostasis) which in turn stimulates the GLUT (the glucose transporter to the cells). The uptake of glucose / feeding of the cells will improve. In my opinion, the improved nutritional condition will cause a whole chain of reactions. See, eg, http://www.ncbi.nlm.nih.gov/pubmed/19494326 to see what all shows up and presumably is "attenuated" if one takes Metformin.

The believe or the way this is seen is that Metformin has anti-inflammatory properties and suppresses immune responses. But is that really true? I think what actually happens is that the nutritional condition of the cells improves and that because of that many neuro-signaling pathways calm down. See, eg, http://www.ncbi.nlm.nih.gov/pubmed/20865368 which suggest such course of action. The underlying concept is very important here and probably could imply a major breakthrough in the thinking about neuro-inflammatory diseases.

Many of the ideas and suggestions that I have seen pass by on this forum would support such line of thought: a hormonal disbalance in MS with higher cortisol production will over time develop an insulin resistance; the Vitamin D which plays a role in the glucose absorption and insulin action; the Vitamin D production in relation to the cholesterol and cortisol; the magnesium and the uptake of glucose; zinc that helps bind the insulin and "supports" the adrenal gland, glucolyse processes in the liver, etc.
Many unknowns here, also how it all relates to each other.

The dimension of micro-cellular feeding should be taken into account and may well underly all kinds of neuro-inflammatory expressions as important signalling pathway for the metabolism to signal there is something wrong (that is the undernourished cells). Future therapies should then be designed from the viewpoint to improve nutrition (pro-nutrition) rather than from the viewpoint to suppress or attenuate the inflammation (anti-inflammatory). This would be a very fundamental shift in the thinking, perhaps even needs a complete rewrite of the medical doctrine.
Last edited by Leonard on Thu May 12, 2011 11:49 am, edited 1 time in total.
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Postby Leonard » Thu May 12, 2011 11:48 am

I think there is a local issue and a global issue.

The local problem lies with the local stenoses and narrowings of the vessels. The reaction of the immune system will ultimately be seen as the characteristic lesions. The nerves there will be conducting somewhat less causing all our known motor problems. By opening the vessels, the things will stabilize. And those with RR will recover somewhat.

The global problem is that of absorption of glucose by the cells. That's a wider problem that may occur throughout the body. Here are neurons as well as muscle cells involved. The GLUT (glucose transporter) may play a crucial role here. These are things that will normally only become apparent when you get diabetes2.

But we have from birth (for me that is for sure) had stenoses and lesions have formed during our childhood. Conduction from the brains is already weakened especially in places where the lesions are located. By mid age a problem of impaired glucose absorption adds to this further weakening the nerve conduction (the hypothesis of this entire thread). Patients with diabetes have very similar neurological symptoms like numbness pointing towards weaker conduction.

I thought it was due to calcification and insulin resistance. But I think now that the real mechanism is the GLUT. The GLUT can be displaced (translocation) by cortisol (for fight or flight). And thus they regulate the ability of cells to take up glucose, in fact how the metabolism works (glucose or fat burning). Repeated cortisol/insulin action because of stress, high sugar and insulin peaks - and age of course - are not good and may detoriate the functioning of translocators and increase insulin resistance.

That there is really memory / hysteresis in the GLUT:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755292/

This seems consistent with the advice of some old and wise neurologists (who knew the real style rather than being forced by the modern protocols and medicine) not to use sugar when diagnosed with MS. And also why people with diabetes2, if they do not use any sugar and e.g. Metformin, are able to stabilize.

This also seems to match my own experiences. If it is really warm, I do not go so well. But if I take a dive in the swimming pool and cool down, I go really very well, at least for a while. The temperature effect on the glucose metabolism and the insulin sensitivity is known.
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Postby Leonard » Sun May 15, 2011 4:09 am

This publication in Neurology is an important step away from the auto-immune paradigm. Although the article is cautious in that it makes reference to vascular co-morbidity, the issue of micro-cellular feeding and ccsvi/low-glucose is coming ever closer.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848107/

From wikipedia: In medicine, comorbidity is either the presence of one or more disorders (or diseases) in addition to a primary disease or disorder, or the effect or Additional Such disorders or diseases.
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Postby Leonard » Thu May 19, 2011 5:39 am

The GLUT (glucose transporter) can be moved across the cell membrane by cortisol / adrenaline action. It brings the metabolism in a fight or flight mode that aims to ensure maximum opportunity for survival.

But will the GLUT return automatically and fully to the idle state or may some hysteresis develop? If the latter would be the case, glucose transport could become more difficult; one is said to develop insulin resistance (not sure whether the term is entirely appropriate from a conceptual point of view). Metformin seems to help to restore the GLUT and thus help to enhance glucose absorption. The links are in above postings.

This article on the glucose metabolism is very interesting: Glucose hysteresis as a Mechanism of Dietary Restriction, Aging and Disease
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755292/
Glucose Metabolic Fate Regulates Its Own: The Gene Switch Glucose Profile Axis Indicated above, Several lines of evidence Suggested That protective effects of dietary restriction could-be mediated by reduction of glucose [13] leading to changes in glucose utilization [1] through 'metabolic reprogramming protection' [2], but the mechanism mediating thesis effects has remained unclear.
[1] http://www.ncbi.nlm.nih.gov/pubmed/1430849
Dietary restriction alters Characteristics of glucose fuel use
[2] http://www.ncbi.nlm.nih.gov/pubmed/12419851 transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts.

There are many interesting leads in these articles the full scope of which is beyond my capabilities .. But what is clear to me is that sugar free diet to promote the fat burning metabolism is important where because of better micro-cellular nutrition the immune system activity will be quietening down.

Thwe sugar free diet could be an important avenue to explore, possibly in combination with Metformin, one possible avenue as mentioned in this article about the treatment of vascular comorbidities for treating MS.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848107/
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Postby Leonard » Thu May 19, 2011 6:04 am

quote from the wonderful book The Cholesterol Hype by Malcolm Kendrick:

An effect of cortisol is that it strongly suppresses the immune system. I have no idea why it does that. But it simply does that and therefore it is used in diseases which are (partly) caused by an overactive immune response. Such 'auto-immune diseases' include..

unquote

Let us for a moment assume that the suppression effect is seen the wrong around. That this immuno-suppression is in fact nothing else that a pro-nutrition, an improved micro-cellular feeding (as I have argued above a few times.)

The cells in our brain screamed for years for food (due to low blood flow / CCSVI). The body will see that and encourage better nutrition. So the cortisol goes up, no of course not to suppress, but to improve the feeding of cells.

Quote again: Elevated cortisol levels influence:

- muscle mass and fat distribution
- increased VLDL levels
- low HDL levels
- elevated LDL levels
- hypertension
- increased fibrogen level (coagulation)
- increased PAI-1 levels (coagulation)
- increased levels Von Willebrand factor (coagulation)
- elevated Lp (a) content (coagulation)
- and ultimately increased blood sugar, insulin levels and insulin resistance (diabetes2).

unquote

Recognise this?
Well I recognize the HDL / LDL balance.
Hughes syndrome is often seen with MS.
Matters such as reduced muscle mass are known for MS patients.
And of course there is the diabetes link.

All a matter of coincidence? I do not think so.
MS a combination of vascular strictures/ccsvi (local) and vascular comorbidities (global)? perhaps
MS a combination of vascular strictures (local) and poor micro-cellular feeding conditions (global)? more likely.
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Postby gainsbourg » Thu May 19, 2011 11:35 am

Leonard wrote:An effect of cortisol is that it strongly suppresses the immune system. I have no idea why it does that.


I believe this is because the human body has to prioritise its resources. The immune system uses up a huge amount of energy and resources. When there is a prolonged life or death situation (from a preditor or other humans) it needs cortisol to enable a continual fight or flight readiness. The immune system is allowed to run down - it simply has to take a back seat.

This is why people get sick or sicker when they do not cope well with chronic stress. Stress is the biggest killer of them all.

But then nature can be very cruel - failure to cope with stress is not useful in nature's eyes. This may not be a 'design flaw' in the human body at all. It may simply be yet another form of natural selection by which nature culls the weakest or most vulnerable members of any species. Nature does not want to encourage animals that cannot cope with prolonged danger, or who choose to colonise areas where danger is constant. This may be why humans have not yet evolved so they can experience prolonged "modern" stress without becoming sick.

I am glad you brought up the hazzards of prolonged stress. Society should make learning to cope with stress a big priority, rather than see it as a simply a low priority 'self improvement fad'
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Postby Leonard » Fri May 20, 2011 12:17 am

We can not be in a flight or fight mode all the time. Normally, the metabolism needs to get back to rest. Now I know modern society causes stresses to be much more prolongued for all sort of reasons (see e.g. the book the Cholesterol Hype by Malcolm Kendrick). Much more prolongued than what the old age man in the cage used to experience. And we use much more sugars to boost the system.

But I believe for us as MS patients, there is more to it. Our metabolism has been put 'artificially' in a fight or flight mode since our childhood. The corticol level was put up to improve the nutritional situation of these undernourished cells in our cerebro-spinal. The undernourishment was caused by the poor blood flow due to the venous insufficiency.

By the same token, I guess our metabolism will -besides trying to improve the nutritional situation (the fuel supply)- try to improve the running of the machine itself (add oil), that is to let the power generators of our cells (the mitochondria) run smoother. That is what is has learned after 100's of million years of evolution, to maintain itself.

To improve the running of the mitochondria requires the CoQ10 and for that we need the Vitamines in the B complex. Now I seem to believe that the vitamine B12 is consistently low in MS patients, certainly that was the case for myself. Why is that? Of course, the metabolism does what it can to better oil the machine and uses Vit B for that. And then leading to a depletion.. I am sure the signalling pathways will be there after 100's of millions years..

It seems if you take MS from a nutritional point of view or better to say the lack of nutrition/oil at the micro-cellular level, all the things just make sense, and all the pieces seem to fit so neatly... That can not be a coincidence anymore ..
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Postby Leonard » Sat May 21, 2011 5:17 am

from the thread on: Pregnancy and Vitamin D may protect against MS - studies
http://www.thisisms.com/ftopict-16652.html

squiffy2 wrote:Image

Tasmanian researchers have found that delaying pregnancy may increase the likelihood of women getting multiple sclerosis.

A yet to be published study looking at MS over the last 60 years has found the frequency of the disease has risen dramatically and it's largely been driven by women.

The Menzies Research Institute's Associate Professor, Bruce Taylor, says delaying pregnancy could be having an impact.

"We think that having children is protective for having MS, He said.... Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/1936




Hallo America, wake up! Start to think wider, more conceptual, don't get lost or trapped in technical details of MS lesions, in biological processes in areas where things have already gone terribly wrong.

What is the common factor of pregnancy and Vitamin D: exactly, the micro-cellular feeding is improved. The whole pregnancy is about nothing else than micro-cellular feeding. The Vitamin D enhances the grips of the insulin on the cells and thereby improves the micro-cellular feeding. Both have anti-inflammatory properties? This may seem to be the case but what happens in reality is that the feeding of the cells is improved and the neuro signalling pathways calm down because of that.

In this same context, this is interesting:

In 1949, Dr. Hench first applied steriods for a purpose other than the substitution in people who have a deficiency of this hormone creation. She gave it to patients with polyarthritis, with good results. In fact they had seen that women who are pregnant and have rheumatism problems, during pregnancy usually have less or no rheumatism.

On the other hand it was known that during pregnancy the adrenal glands produce more cortisol. Dr. Hench found that the arthritis may have been suppressed by increased cortisol production and that proved right. Gradually it was discovered that cortisone has strong anti-inflammatory properties and the knowledge about steroids and their action was developed further...

From this time onwards, the anti-inflammatory aspects have been seen. I guess also by the neurologists who's discipline started to develop around more or less the same timeframe.

But is this true? Is this conceptually correct? Perhaps, it is the other way around. Perhaps this is not anti-inflammation by suppression but neuro-signalling pathways that calm down because of better nutrition of the cells. Most certainly, if seen in the context of a pregnancy which is all about feeding, or if seen from a more conceptual point of view, this much more likely to do with enhanced feeding of the cells.

I think the medical world must urgently rewrite the doctrine (and the underlying concept) from an inflammation suppression (anti-inflammation) to an enhanced nutrition (pro-nutrition).

With that, our understanding of what is MS will change to become a new paradigm closely aligned with the low glucose hypothesis described on this thread.
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Postby Leonard » Mon May 23, 2011 12:37 am

from
http://www.cocir.org/uploads/documents/ ... rev_nd.pdf

.. encouraging a proactive [ technology- ] pull by users, rather than just a [ technology- ] push by suppliers/providers is required for innovative technologies to have maximum transformational effect.
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Postby gainsbourg » Mon May 23, 2011 1:49 am

MS will change to become a new paradigm closely aligned with the low glucose hypothesis described on this thread.


I've contributed to this thread two or three times because it intrigues me that someone has a similar view about MS to my own. You so often mention glucose, cortisol etc. The main difference is that you are approaching it in the same way that all theorists on MS do. You are ignoring the concept of "strain" (or stress if you like).

If you run any fuel driven machine, you can predict the amount of fuel it will consume. If you constantly run the machine too hard (chronic stress/strain) it will demand more fuel than it was designed to use (think chronic, modern stress) - don't be surprised if your machine starts to develop chronic faults that eventually prevent it from properly absorbing even the regular amount of fuel.

Doctors/researchers do not like the concept of strain/stress in medicine, because it is notoriously hard to measure. Instead they feel more comfortable assuming that the human machine (in this case the white matter of the brain) must be developing faults soley due to genetic flaw or microbes.

So why did the human 'white matter' machine behave so well until 150 years ago and become progressively more prone to MS over the last 50 years or so? It is because it was not designed for the type of chronic, modern stress it endures. You can break it down to a molecular level and predict which part of neuronal metabolism/mechanism breaks down (e.g. glucose metabolism) and why... but for me the primary cause is stess.

True, most human machines who inhabit the western world endure the same amount of modern stress yet they are not afected - so there are obviously other, crucial factors that are coming into play. Even so, I believe the ultimate trigger is stress and that anything that helps those with MS cope better with chronic stress is the way forward.

This is why stress so often precipitates MS attacks.



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Postby Leonard » Mon May 23, 2011 2:12 am

Thanks Gainsbourg. You are right, stress is an important factor. And you are right that modern medicine does not know very well how to handle this.

But I believe for us as MS patients, there is more to it. That is to say that conceptually the factor stress can and should be understood in a wider context of what is happening inside our metabolism.

I copy from my posting of Fri May 20, 2011 7:17 am:
Our metabolism has been put 'artificially' in a fight or flight mode since our childhood. The corticol level was put up to improve the nutritional situation of these undernourished cells in our cerebro-spinal. The undernourishment was caused by the poor blood flow due to the venous insufficiency.

So, because of the stenoses, you may be "running low" already for many years or even decades as regards the cellular nutrition in the brain. At that point, stress can tip the balance or -like was the case for me- a combination of stress and massive chocolate consumption (the latter to boost the system but in fact causing the blood flow to slow down even further with disastrous effect…) And my story is not unique there ...
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Postby gainsbourg » Mon May 23, 2011 9:59 am

The undernourishment was caused by the poor blood flow due to the venous insufficiency.


I'm sorry I can't agree with you there Leonard, if you have read my posts elsewhere on this forum, you will know that I was one of the original CCSVI sceptics. Venous abnormalities have been found in roughly a quarter of healthy controls in all studies apart from Zamboni's. This means that CCSVI is more common in the population at large than being left handed - yet only 0.001% of the world's population develops MS.

This doesn't mean that improving blood flow to the CNS will not improve MS symptoms - I'm sure it does in some cases.

In my opinion the "undernourishment" of the white matter is brought about by chronic over-use, which in turn is the result of chronic modern stress. Primitive tribes people and the majority of Eastern cultures do not get MS - despite getting plenty of sunshine by the way - it is because they do not have to endure the unnatural "chronic western stress"

Recent research into heart disease by Shen et al (2008) confirmed that people who have had long lasting anxiety are 30-40% more likely to suffer a heart attack...yet we do not know why. Yes they measure cortisol levels, and so on, looking for how stress might affect cardiac tissue. i.e. a biochemical explanation. I believe researchers ignore the stress/brain link purely because it is much harder to measure.
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Postby tara97 » Thu May 26, 2011 3:53 pm

I have a wild theory about the ccsvi. low cortisol equals low blood pressure and orthostatic hypotension. what if the venous insufficiency is a compensation mechanism somehow the body wants to perserve bloodflow to the brain. I know thats far fetched but I think orthostaic hypotension is part of the ccsvi mechanism some how
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Postby Leonard » Fri May 27, 2011 1:29 am

tara97 wrote:I have a wild theory about the ccsvi. low cortisol equals low blood pressure and orthostatic hypotension. what if the venous insufficiency is a compensation mechanism somehow the body wants to perserve bloodflow to the brain. I know thats far fetched but I think orthostaic hypotension is part of the ccsvi mechanism some how


thank you, this crossed my mind as well.

I would contend that the venous insufficiency is there first. We know that >90% of the young people on Sardinia that Zamboni diagnosed with venous problems in the neck developed MS later on when adults.

This is consistent with my own experiences. The narrowings of my IJVs were clear "mechanical" deficiencies. I believe many IRs that do the liberation procedure have similar experiences.

My father had three attacks of Meniere (I think this is caused by vascular narrowings behind the ear causing a local "auto-immune" reaction). One of my narrowings was behind the same ear. This may point to a “genetic susceptibility”: http://www.areco.org/ms.pdf

But with you I do believe that the metabolism has developed many compensatory mechanisms over the 100's of million years of evolution and that we know only a small proportion of it ("the 4% world; 96% dark").

I could imagine that cortisol comes somewhere into the picture e.g. to reduce blood pressure, to increase insulin to improve micro-cellular feeding conditions, to make the body run on a glucose burning (easier to get this fuel..) rather than to promote the glycolysis of fatty acids (normal mode), low on B12/B6 as vitamines are taken to oil the mitochondria? etc

It is here where all things start to relate to each other. I am sure there is much to learn here…
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