A new concept and treatment options for MS

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A new concept and treatment options for MS

Postby Leonard » Sat Jan 08, 2011 1:57 am

This is my best assessment of what is MS (update 18 September 2014).

The Human Endogenous Retro Virus (HERV) of the W-family is central to the development of MS as well as many other immune diseases. Herpes simplex, Varicella Zoster (VZV) and Epstein-Barr (EBV) are members of the family. During periods that people are immune compromised (can be the fetal period, the period of the newborn and immune deficient periods), the viruses can incorporate some of their genes in the DNA of permissible cells.

Immune deficient periods relate to the health of the intestine. Our diet (bad fats, gluten, low quality food) and our modern habitat (hygiene, lack of immune training) weaken the immune system. The immune system also weakens with age. A weakening immune system may initiate a vicious circle with poor gut health, enzyme and bacterial imbalances which will allow viruses and fungi to get out of control, and which affects the HPA axis lowering cortisol production in turn aggravating gut function. As such, the virus itself is not programmed to reactivate at specific time intervals but it is the immune system that weakens.

The gene transduction occurs during immune deficiency periods (this concerns newly infected cells, this does not refer to the 8% transgenic cells from the genome work). The incorporated viral genes (transgenes) are tolerant to the body or no immune memory against these transgenes has established. In MS, in particular the oligodendrocyte precursor cells (OPCs) will be infected. These oligodendrocytic stem cells and their progenitors are preferred by the virus because they differentiate and help replicate the virus. CCSVI is a factor that broke the BBB tissue much earlier.

People with transgenes in their body are healthy but predisposed to develop a disease. For instance, Crohn's disease is associated with measles. People predisposed to develop MS will become diseased when they are infected with a microbe that shares epitodes with the transgenes present in the OPCs. A chronic low-level EBV/VZV/Herpes infection/inflammation will cause such an immunological reaction. Vaccinations (e.g. Hepatitis) are also suspect.

Specific T- and B-cells will pass the CNS and cross-react with the transgenes in the OPCs (my count of EBV/Herpes B-cells is very high). Due to this cross-reaction, many OPCs will die which leads to a diminishing number of OPCs, of dendrocytes and a reduced myelination of neurons.

During this cross-reaction, many mediators will be released by the infiltrating T-cells. This will increase angiogenesis and cause hyperproliferation of surrounding tissue cells in the CNS which in turn causes the pathological lesions (sclerotic plaques) typical for MS.

The symptoms of MS will be mild in relapse-remitting MS but severe in progressive MS depending on the kind of virus that has incorporated part of its genome in the oligodendrocytic stem cells. Inflammatory viruses such as VZV will be associated with mild diseases whereas onco viruses such as EBV will be associated with severe diseases.


Personally I do not exclude the possibility that VZV prepares the path for EBV (microbleedings, angiopathy). And that the second peak in the age of onset is related to the EBV that starts to take its share.

I am very grateful to the eminent immunologist whom I consulted earlier this year for sharing this concept with me, the viral tolerance theory.

Besides the immune reaction against the OPCs, the high load of immune complexes has a second important effect. The lack of energy in MS and other lesions is a co-morbidity factor caused by the high immune complexes, the superoxide that reacts with nitric oxide and forms peroxinitrate, poisoning lipids, inhibiting ADP to ATP conversion (biochemical reaction hypothesis Scott/Pall). Hence, the fatigue typical for MS patients may be caused by the same chronic EBV infection but with a completely different underlying mechanism than the plaques in the brains. Because of high titers, I am eating my own muscles and with that also the connection between nerves and muscles; this is possibly an effect as important as the disconnect in the brains.

In my view, the main components of a therapy are to surpress the virus without reactivating it (e.g. by anti-HIV medication) and to resurrect the immune system (Pender, IgG3).

In the short term, a low-fat diet (Swank, low butyrate SCFA to stop EBV replication in the gut) and a 'vegetable' diet (Wahls flavonoids/Campbell fermented foods) will help strengthen the immune system (>90% of the immune system is in the gut). And possibly NMES to build muscle strength.

I keep the update below as I think there is still value in it.

=========
update 28 July 2014

I would like to recap based on our learnings.

MS has many aetiologies. The picture is not black and white. MS is multifacetted with considerable variation among patients (the NO / OHNOO cycle interacts with distinct tissues to produce varying patterns of symptoms and signs) http://www.allergyresearchgroup.com/Exp ... sp-35.html . Variation may also be seen in pattern/degree of ccsvi, immune system handling of EBV and gradations of ADMA generation by the kidney/renal system.

Our system for health care (and the thinking inside it) is locked up in a grid, no one has the power and democratic legitimacy needed to take control. The pattern of thinking by most medical experts is too linear / singular rather than lateral / heterogeneous. We need to break out of the situation: http://en.wikipedia.org/wiki/Paul_Feyerabend Everybody wants a magic bullet but for MS that does not work. Doctors should have a veterinarian look at things. As regards the therapy, it is the sum of all the things you do that makes a difference and it will take time to be effective.

In MS, the energy metabolism is disrupted with reduced absorption of essential nutrients. But most studies on MS get lost in the complexity at the back of the mechanism, a mechanism that does not even have to be fully understood. At the front we find the high EBV load, the vicious NO / OHNOO cycle, oxidative stress, peroxinitrite that jams the cells etc. The approach should focus on the front, not on the back! Virology and biochemistry are primary; neurology and endocrinology are secondary.

Ccsvi links the drainage of the dural nerve system, the dural sinuses, and meningeal inflammation. It provides a possible explanation for meningeal inflammation and subpial cortical lesions exclusively observed in MS patients. Environmental factors such as exposure to heavy metals (even of previous generations) and related genetic factors of veins may play their role here (Boston document, Texas study). Still apart from the whole amalgam discussion, PwMS also seem to have a worse than average dental health which may find its explanation here as well.

Quite a bit of research implicates EBV is central in the development of MS. One ingenious study looked at blood samples collected from 3 million US military personnel at their time of enlistment, and their subsequent development of MS. Those who had high anti-bodies to EBV at the time of enlistment, that is those who had a chronic viral infection, even up to 5 years before the onset of MS, had a 20-30 times higher risk of getting the disease than those with low antibody levels.

Researchers in Houston, Texas have speculated that some of the effects of interferons in MS might be due to their anti-viral properties (in fact as much as their effects on the immune system).

In susceptible people, or it is probably better to say people that have a certain predisposition, that is those with the 'right' genetic make-up, and the right sort of environmental triggers e.g. lack of sunshine, fish oil, infection with EBV may trigger the onset of the disease later in life. The kidney/renal system producing ADMA is a highly suspect factor predisposing people.

The mechanisms causing disability progression and the lesions are only loosely coupled: the EBV envelop protein vs EBV infected B cells inducing peroxynitrite nitrating the lipids. Studies also confirm that disability progression and lesions are not 1:1 correlated.

Autoimmunity is explained by chronic high concentration EBV immune complexes cross-coupling with epitodes of EBV remnants in transgenetic cells. About 8% of cells in our body is transgenetic, after about 120 million years of evolution.

In MS disability progression, because the effects of poor health of dendrocytes and a lack of energy come together, they appear one and the same process. But I think underlying are in fact two different processes: the EBV envelop protein causing the replenishment of new dendrocytes to stall vs peroxynitrite disabling glyceraldehyde-3-phosphate and ADP/ATP conversion causing mitochondrial energy / the pump to fail. In casu, I see my own disability progress but at the same time to migrate more and more towards an energy failure. And although there is a common causal factor, they are different processes. An explanation for the big temperature effects seen in Pw MS -who inevitably run more on the borderline- should probably be sought in this corner as well.

The count of mitochondria in our cells is important too. If you have more mitochondria and active membranes, you are less susceptible for developing MS, I think because it just takes longer for the system to get jammed. The number is proprotionate to the vitamin D level in the circulation of the mother from say the 2nd to the 6th month of pregnancy and of the adolecent during the main phase of cellular growth. Where the vitamin D level is influenced by cholesterol and sunlight. That is why I think that our modern low fat diet that may be good for mid-aged and elderly people and helps protect against heart disease etc is not necessarily good for young mothers and children.

Women are reported to produce more nitric oxide than men, possibly explaining the gender bias seen in MS. A similar gender bias is seen in autoimmune diseases characterized by excessive peroxynitrite (i.e. CFS, lupus, rheumatoid arthritis).

Nitric oxide is known to stimulate the nociceptors that initiate the perception of pain. I am sure nitric oxide is sky high in MS patients explaining pain in the limbs.

According one article, a low-fat diet inhibits replication of the virus and thus helps to keep the virus/B-cell count down. A sustained low-fat diet (for half a year or more) will improve the gut flora (from personal experience my gut flora and control stabilised - unexpectedly) which suggests a better working of the immune system (>90% of the immune system is in the gut; the name Natasha Campbell comes to mind) and with that a better virus 'control' (Swank). Besides diet, in general the immune system weakens with age where an already weak immune function will get weaker faster.

The cycle seems self-reinforcing: EBV infection gives ever weaker immune protection which aggravates EBV infection. Strengthening the immune function would seem central to any therapy.

I find the theory Beyond Avonex and Valtrex by Scott on regimens-f22/topic24019.html beautiful thinking and highly plausible as it connects all the things that I see in my own family. It is fully complementary to and reinforces the overall concept below. I cannot be naïve anymore and simply accept that this is all coincidence. It is just too good to be dismissed. I encourage you all to read Scott's theory.

Perverse drivers in the medical system and fear of stepping outside accepted practice hamper the exploration of new ideas. Fortunately, the collective cognition on the Internet leads to new concepts beyond old thinking in traditional quarters. Together with prof. Peter Finke http://www.perlentaucher.de/buch/peter- ... ience.html , we can only hope that this citizen science that now thrives on social fora may find "ways out of the impasse of reality".




A new concept and treatment options for MS II

update 29 April 2014

1. Causes

MS has multiple aetiologies

CCSVI (probably in part a birth defect) positively correlates with MS (1)
and is a factor that contributes to an early compromise of the BBB

Venous reflux/hypoperfusion combined with weakening immune system (see also point 3. below):
- promotes local inflammatory processes (2)
- reactivates HERV-W (Herpes, VZV, EBV) in cerebral meninges (as in cartilage of joint as in RA)

With broken BBB:
- Phase 1: Herpes simplex/VZV or Cpn blocks receptors --> inflammation --> RR (time constant days to weeks)
The virus may be latent for many years and reactivate only sporadically after so many years. In the beginning, for me reactiviation repeated only every 8 or 9 years, always in the Spring when the immune system is low.

- Phase 2: HERV Herpes/VZV/EBV --> injury of cell types i.e. dendrocytes --> progressive (time constant months to years)
VZV causes micro vasculopathy http://download.springer.com/static/pdf ... 7&ext=.pdf
B-cells release toxic substance that cause death of differentiated oligodendrocytes http://www.ncbi.nlm.nih.gov/pubmed/22458983
EBV envelop protein inhibits OPC differentiation; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672075/
EBV promotes the proliferation of Peroxynitrite that is by far the worst free radical, poisoning the system in several ways e.g. causing mitochondrial failure, nitrating fat tissue giving rise to inflammation (lesions in combination with fats?) etc... see also Part III below and regimens-f22/topic24019.html

The problem of demyelination -which is the real problem in MS, studies have clearly shown this- may well be a bit more than the envelop protein e.g. be intermingled in some way with virus, fats, B-cell immune complexes, peroxinitrite and ADP/ATP. But for now and for the overall concept that does not seem so important.

Graph of age of onset of MS has double peak --> different mechanisms underlie Ph1 and Ph2;
Ph2 is age dependent, not on RR severity

(1) CCSVI = Venous insufficiency of Internal Jugular Veins in the neck, draining the Cerebro Spinal
(2) Local inflammatory processes combined with inflammation induced high levels of nitric oxide cause narrowing of cerebral veins and autonomous nervous system dysfunction


2. Auto-immunity

Uncontrolled EBV infection reactivates in ectopic B-cell follicles in cerebral meninges --> chronically active EBV

Infection of autoreactive B-cells

Elevated EBV anti-bodies (already years before the first MS symptoms begin)

Cross-coupling of immune complexes with epitodes of remnant virus parts (in transgenic cells) explains the action against the "self"
- is secondary process (The MSRV-Env protein has also pro-inflammatory properties which translate into the production of different cytokines)
- EBV is chronic; immune complexes not effective against EBV; fat metabolism involved in EBV replication

Note: Chronically active EBV presents
- coronary artery aneurysm (uncle, farther's cousin)
- nasopharyngeal carcinoma (grand farther)
- Meniere (farther)
- mitochondrial energy failure? (brother)
- MS (me, with very high readings of Herpes simplex and EBV immune)


3. Weakening immune system

Immune system gets ever weaker <-- mitochondria get weaker
(poor quality of food e.g. high carb, lack of phytonutrients, stress, lack of sunshine/vit D/fat, environment, vaccinations, HERV/EBV)

Immune system is producing useless /non-working antibodies against EBV

B-lymphocytes unbridled multiplication

Hypo gamma globulin (shortage IgG3)

Immune system forgets about the rest

Chronic infection, for example:
- leaky gut --> Ɛ toxin
- mycoplasma
- Cpn infection (in RR)
- even toenails fungus which has crossed here several times

Diagnosis:
- CFS
- Rheuma Arthritis
- Lupus
- MS

- Autonomic dysfunction smooth muscle layer
(my own titre was very high, eating own muscles, is this the regulatory system attempting to relax smooth muscle of cerebral veins?)

4. Treatment options

Main options:

Lots and lots of antioxidants and flavonoids (incl. supplements such as CoQ10) see the list on http://www.prohealth.com/library/showar ... ibid=17947

Neuro Muscular Electric Stimulation (NMES) general-discussion-f1/topic24974.html
for nutrients and NMES see also pg 14-17 of http://www.ms-uk.org/files/npwm_2009_0053.pdf

Hormonal and amino acid support as L-Arginine

Anti-viral as Valacyclovir (as long-term treatment option); in the short term, valacyclovir may cause a reactivation of the virus

Gamma globulin IgG3

------

Other issues for consideration:

Vitamin D gut/immune system support
Vit A to help restore gut function

Nutritional support / diet
Detoxification for strong mitochondria; strenghten B-cells, epithelium, meninges
Food rich in anti oxidants incl. polyphenols, acathpocyanids (bue black), lutein (red) and caretnoids (yellow orange)
CoQ10 (e.g. MitoQ effective form)
High quality food phyto nutritients
Oxygen in bed room (when at rest in supine position)
Low fat / Swank / FAS = EBV inhibit (Fatty Acid Synthase inhibitor, no palmitoylated proteins, no palmitic acid)
Magnesium Zinc

Promote brain perfusion
stimulate Chinese 'axis'; electrically stimulate vagus nerve (as in RA)
Prozac derivative
Bosenthal

Hormonal support
Arginine
DHEA
Testosterone
HPA axis
Adrenal – cortisol - gut

Anti viral (e.g. Zovirax/acyclovir or Valacyclovar or anti-HIV/HAART)?

Anti biotics – Cpn RR

Gamma globulin IgG3 to help normalise the immune system



A new concept and treatment options for MS III

Scott1 wrote:
I'm afraid the acyclovir is a long term treatment. I took 500g twice a day, every day, for a decade. The reason is the active life of single tablet is around 15 hours and you need to work on total cover. All it does is put a stop in the codan of the RNA of the EBV so when your B cells divide you can make an uninfected B cell instead of an EBV immortalized cell. The reason you want to limit the EBV proliferation is an EBV infected B cell gives off two molecules of oxygen (superoxide). Whilst we need superoxide to control pathogens we don't need an overproduction of it.

I think the reason why some people don't develop MS and we do tell us that EBV is not the whole story. The other part is the so called predisposition. My thinking is this condition is due to our kidney/renal system producing asymmetric dimethylarginine (ADMA) whereas healthy people produce the symmetrical form. ADMA is an endogenous inhibitor of all forms of Nitric Oxide synthase. The capacity to vasodilate is dependent on how much endothelial Nitric Oxide synthase we have to make Nitric Oxide. In people with MS there is a very high level of inducible Nitric Oxide synthase (iNOS) rather than endothelial (eNOS).

iNOS is made by the body in response to injury. The ADMA depletes eNOS and iNOS arises as a natural response. Why is this important? When superoxide and Nitric Oxide come into close proximity they spontaneously make Peroxynitrite which is, by far, the worst free radical. Peroxynitrite mucks up many functions as well as nitrating the lipids. The most important factor is the disabling of Glyceraldehyde-3-phosphate. If this doesn't function, ADP can't become ATP. We need ATP to drive the sodium-potassium pump in each cell. If that doesn't function we can't make energy.

EBV contributes superoxide toward the production of peroxynitrite, but if you have a renal malfunction that is producing ADMA leading to too much iNOS ,you are likely become compromised as an MS person when the peroxynitrite runs rampant.
The lack of energy is due to the collapse of the function of the pump as is the loss of mitochondrial vitality. The inability to vasodilate is due to the lack of Arginine. The lack of Arginine is due to a renal malfunction.

The renal problem may be as simple as late maturity of function or we may have a mutant form of Megalin. I often read posts about Vitamins D, B12 and A. They are all transported through the renal proximal tube by Megalin where some metabolizing occurs. Vitamin A is sorely lacking in the general conversation but it is very involved in gut health.

I prefer to break the problem into two separate issues 1) a renal problem and 2) a viral infection that promotes the proliferation of Peroxynitrite that poisons the system. I posted a unfortunately long winded explanation called "Beyond Avonex and Valtrex" which goes into more detail with links to research.



see also regimens-f22/topic24019.html


-------------------------------------------------------------------------------------------
The original first posting of 8 January 2011 starts here:

This is a copy of my posting on the thread on ccsvi:

It is hypothesised that multiple sclerosis (MS) is caused by an insufficient glucose level in the brain or parts of the brain.

Patients with MS are consuming more sugar than the average person, to get it elevated in our blood streams, to try and meet the unmet needs of the brain. And the result of greater sugar consumption is a greater prevalence of chronic yeast infections and symptoms as candida . Also the faster recovery of motor functions of MS patients on the intake of sugar/glucose, in particular in the beginning, would seem to suggest a glucose link. Furthermore, it is an explanation for the fast recovery of some patients post- ccsvi liberation and a post-liberation increase in dreams and REM sleep, since REM has high glucose demands.

The blood flow delivers oxygen and glucose to the very hungry brain as well as other nutrients, and takes away waste products. A lack of glucose puts the neurons in a dormant state; they become under-nourished. The consequence is demyelination and, if seriously under-nourished for a longer period of time, myelin and neuronal death. When this happens, the microglia jump on this and clean up the mess. Once they get out of the BBB, the T-cells jump on them and we start see the scars and the inflammation. That is when MS shows up.

Why are the cells under-nourished? There are at least two reasons: iron deposits on the vessel walls that inhibit the transport of glucose across the BBB and; insulin resistance that inhibits this same transport of glucose. The iron deposition may develop at a young age as a result of problems with the drainage, its origin is probably pre-congenital. The insulin resistance may develop at a later age. MS is probably a consequence of both, in a wide variety of cases among the population. One effect may be a more important for an early age onset and the other for a later age onset. The double peak in the age of onset of MS would indeed suggest the possibility of such underlying mechanism [there are two peaks on the age of onset graph at 25-30 and 40-45 http://newsgroups.derkeiler.com/Archive ... 01256.html ].

Stenoses in the veins draining the brain and spinal column (ccsvi, Zamboni) cause refluxes in the deep cerebral veins and will lead to iron deposition on the vessel walls (you can see this on 7T MRI) and this inhibits glucose transport through the affected parts of the BBB. Iron deposition is a normal phenomenon in organs and limbs in case of problems with the drainage that has been known for a long time. By opening up the blockages in the veins by angioplasty, the blood flow can restore to normal, and eventually as the iron is taken away the BBB function may restore to normal. The increased blood flow during pregnancy and stop of MS progression adds to the plausibility of the concept. The low fat/Swank diet and the use of blood thinners/anti-clotting (effect Copaxone?) may also help improve the blood flow with the same positive effects.

Some persons may already have a fairly weak glucose condition in their brain due to the low blood flow through the head and the iron depositions. At mid age then, the insulin resistance starts to develop and the glucose transport will be further weakened. The Vitamine D relationship, well known in MS, plays its role here.

As studies found, higher levels of Vitamine D (childhood and/or during pre-congenital phase) may delay the onset of MS a bit because of lower intra-cellular calcium levels where insulin resistance and problems with glucose transport will develop a bit later on. Conversely, lower levels of Vitamine D will elevate intra-cellular calcium levels where insulin resistance develops earlier on and thus impaired glucose transport across the BBB will develop earlier.

This may explain the differences found among MS patients and a control group that were screened for ccsvi: people who have stenoses and therefore a low blood flow but high Vitamine D will still provide enough glucose to their neurons and myeline, and therefore will not experience the MS symptoms, or at the very least not as quick as those with low Vitamine D. The prevalence of diabetes type 2 in MS patients would further suggest a link with the insulin resistance. It is also known that this insulin resistance develops long before the signs of diabetes become apparent and the diabetes type 2 is diagnosed, further adding to this part of the hypothesis.

Studies have also found that a low-glucose condition causes or at the very least it is likely to cause demyelination. The process of demyelination is already well underway before diabetes type 2 shows up.

Also it ties in with the effect of heat on glucose in the bloodstream (it fluctuates more wildly; diabetics have to account for this in the summer) and, if overheated, the brain will endure worse damage from this lack of glucose.


What lessons may we draw:

1. get the veins opened and restore the normal blood flow. This will increase the volume of blood, and improve the cerebral hypoxia side of the equation, and the cerebral hypoglycemia side. The iron deposits may be taken away (?)

2. if appropriate and confirmed, start taking (diabetes type 2?) medication early on to overcome insulin resistance and improve the glucose transport across the BBB. And also, get the blood sugar level back to normal.
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Postby lyndacarol » Sat Jan 08, 2011 12:52 pm

I see validity in this line of thinking with the mention of insulin resistance – insulin resistance is marked by an increase in the secretion of insulin, i.e., excess insulin.

By the way, I think a new peak has developed in pediatric patients. I believe six pediatric MS centers have been established across the US. I suspect this has happened because younger and younger children are consuming diets of more items that readily convert to glucose, thereby triggering more insulin production.

Old friends here are not surprised by my comments, right?
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Postby Leonard » Tue Jan 11, 2011 2:26 am

@ lindacarol: I think your comment that insulin resistance is marked by an increase in the secretion of insulin, i.e., excess insulin is more than valid, in particular if seen in connection with the high sugar consumption among MS patients!

It might well be that MS with an onset at mid age and diabetes type 2 are two sides of the same coin. In any event, the symptoms of both diseases show a remarkable similarity, which looks more than just a coincidence.
http://diabetes.niddk.nih.gov/dm/pubs/neuropathies/
http://care.diabetesjournals.org/conten ... 984.1.full


@ everyone who is interested, please have a look at

http://www.thisisms.com/ftopic-15083-da ... sc-15.html

The postings on this page explain how we got to the low glucose hypothesis.

thank you to all.
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Postby Daisy3 » Wed Jan 12, 2011 1:26 am

My husband has always been slightly cynical about CCSVI as he could not join the dots between it and MS. Your idea of diabetes has made a light switch come on in his head. He does consume a sickening amount of sugar on a daily basis,he was diagnosed in his late 30's but suffered the symptoms for a good dew years earlier.

I am tempted to get him some metformin from a friend of mine!
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Postby Leonard » Thu Jan 13, 2011 3:08 am

In the beginning of the 1980s, apparently there has been a discussion in the medical community of the connection of multiple sclerosis and diabetes. The discussion was inconclusive and eventually disappeared in the background.

I suppose that at that time, the vein insufficiency and the related low glucose condition were not part of the debate. But now with ccsvi, all this makes sense, and all the pieces of the puzzle come together. The low oxygen O2 also fits in quite nicely. http://www.thisisms.com/ftopict-15235.html

With the (hypo)thesis of this thread, I think we have come very close to unravel the MS mystery.
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Postby Leonard » Mon Jan 17, 2011 3:23 am

I believe that the main discussion on this forum should not concentrate exclusively on the vascular dimension (ref: http://www.thisisms.com/forum-40.html ). The reason why we have taken this discussion so far is that we have been able and willing to look outside the box, that is the box of the neurologists. Now we should not make the systemic failure of locking ourselves into the vascular box. Our primary goal must be to solve the mystery of MS, to find what causes MS and how to best treat it.

Therefore, we must keep our eyes open and continue to look broader, for instance into the low-glucose hypothesis. In fact, MS is a complex disease that to solve it, besides neurologists and vascular doctors, may need to involve other disciplines such as diabetics specialists.

In the beginning of the 1980's there has been a discussion about the links between MS and diabetes. But it was difficult to prove and the issue disappeared in the background. Now with this new ccsvi condition, perhaps the old discussion of the 1980s should be held again, in the right context and against this new background. For further information about the low glucose condition, see: http://www.thisisms.com/ftopict-15181.html

I think the medical world can not get around this low-glucose hypothesis. The explanation given for the double peak in the age of onset makes this highly plausible as a concept. For the rest of the posting, if you do google and bing searches, you will find many recent articles that can confirm every single sentence of the (hypo)thesis.

Therefore, I call on the medical world to investigate the low-glucose hypothesis as part of their efforts. They can deny, deter, defer, delay and try to destroy. But at the end of the day, that will not work because the evidences are there and the pieces of the puzzle just connect too neatly.
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Postby tara97 » Mon Jan 17, 2011 12:17 pm

one thing that does not seem to be impaired in the MS brain is the analytical mind. I originally presented with MS for the first 8 years and then It started to go systemic into sjogrens and then down into lupus. I have spent time on all forums and no group is more intelligent than the MSer. our ability to analyze and delve into abstact thinking is second to none. we definately do not take anything at face value and there for use the persuit of self knowledge to explain everything behind the face. I love it!!!
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Postby lyndacarol » Mon Jan 17, 2011 3:20 pm

As I posted earlier in the CCSVI forum (although I think I feel more comfortable posting it here now):

Leonard – Please give me explanations for these two situations:

#1 Why is the glucose level lower in MS patients; that is, what lowers the glucose level?

Other than a diet low in glucose-making foods, the only answer I can suggest is a high level of insulin that sweeps the glucose out of the bloodstream.

#2 Several years ago there was successful treatment of children with seizures at Johns Hopkins. The treatment was a ketogenic diet (diet high in fats and protein) and did control the seizures. As I recall, the finding was that the brain could function just fine on ketones – that glucose was not necessary for brain function.

In the 1920s anthropologist-turned-Arctic-explorer, Vilhjalmur Stefansson, spent a decade among the Inuit, eating nothing but meat, no vegetables or fruit. His observation was that those who lived on this diet were among the healthiest imaginable. His observations contradicted conventional wisdom at that time that a varied diet was essential for good health. "It is a misconception that the brain and central nervous system require dietary glucose to function." See pages 319-325 of Good Calories Bad Calories by Gary Taubes.

Just today, 1-18-11, on the TV program, The Dr. Oz Show, Dr. Joseph Mercola stated that ketone bodies serve as an alternative fuel source to glucose: about 4:20 in the video at

http://www.doctoroz.com/videos/alternat ... versy-pt-2


I completely agree with you when you said:
I believe that this discussion should not concentrate exclusively on the vascular dimension. The reason why we have taken this discussion so far is that we have been able and willing to look outside the box, that is the box of the neurologists. Now we should not make the systemic failure of locking ourselves into the vascular box. Our primary goal must be to solve the mystery of MS, to find what causes MS and how to best treat it.



I propose we start in the box of endocrinologists.
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Postby Leonard » Tue Jan 18, 2011 2:01 am

tara97 wrote:one thing that does not seem to be impaired in the MS brain is the analytical mind. I originally presented with MS for the first 8 years and then It started to go systemic into sjogrens and then down into lupus. I have spent time on all forums and no group is more intelligent than the MSer. our ability to analyze and delve into abstact thinking is second to none. we definately do not take anything at face value and there for use the persuit of self knowledge to explain everything behind the face. I love it!!!


yes tara, you are right, I see that as well. I think it is 100 million years of evolution that has caused (and forced I might add) the people and their predecessors with a low glucose condition to think more strategic. (could also be that it is merely the evolution of the individual in one generation.) Conversely, those with a high glucose condition will think more of winning the 100 meters today.

I know this is all wild speculation, but it makes sense and supports the low glucose hypothesis, in fact it is another piece of the puzzle that fits in neatly.

thanks for your posting.
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Postby Leonard » Tue Jan 18, 2011 2:52 am

lyndacarol wrote:As I posted earlier in the CCSVI forum (although I think I feel more comfortable posting it here now):

Leonard – Please give me explanations for these two situations:

#1 Why is the glucose level lower in MS patients; that is, what lowers the glucose level?

Other than a diet low in glucose-making foods, the only answer I can suggest is a high level of insulin that sweeps the glucose out of the bloodstream.

#2 Several years ago there was successful treatment of children with seizures at Johns Hopkins. The treatment was a ketogenic diet (diet high in fats and protein) and did control the seizures. As I recall, the finding was that the brain could function just fine on ketones – that glucose was not necessary for brain function.

In the 1920s anthropologist-turned-Arctic-explorer, Vilhjalmur Stefansson, spent a decade among the Inuit, eating nothing but meat, no vegetables or fruit. His observation was that those who lived on this diet were among the healthiest imaginable. His observations contradicted conventional wisdom at that time that a varied diet was essential for good health. "It is a misconception that the brain and central nervous system require dietary glucose to function." See pages 319-325 of Good Calories Bad Calories by Gary Taubes.


I completely agree with you when you said:
I believe that this discussion should not concentrate exclusively on the vascular dimension. The reason why we have taken this discussion so far is that we have been able and willing to look outside the box, that is the box of the neurologists. Now we should not make the systemic failure of locking ourselves into the vascular box. Our primary goal must be to solve the mystery of MS, to find what causes MS and how to best treat it.



I propose we start in the box of endocrinologists.


@ lyndacarol: The low glucose condition (not in the blood but in the cells of the cerebro-spinal) may have a number of causes where we see a large variability among the population: low blood flow, iron deposition, and increased insulin resistance. Also an impaired transport of oxygen may be a factor.

The first posting of this thread sets out the concept. I know, it may not be the perfect English (I am Dutch) and in the Internet age we are more used to scan rather than to read (I am no different). I would encourage everyone to really read and analyse the first posting of this thread. You will get the gist and get to understand what are the major pieces of the puzzle. [sorry about that :wink: ]

Your second point is very interesting: perhaps cells can be fed with other nutrition than glucose. but one thing is clear: they will have to be fed one way or the other as otherwise they will become under-nourished, go into a dormant mode and eventually die. so perhaps we should talk about low-nutrition condition of the brain? whow, we are making new connections here... notwithstanding, the glucose conditions will likely remain to be a main piece of the puzzle as it explains so neatly the double peak in the age of onset.

On your proposal to start in the box of endocrinologists: I did not know the word and looked it up at wikipedia. I agree, this is a discipline that should be part of the discussion, just like diabetes specialists. But I do not agree with some of the postings on some of the other threads that we should leave each group at its own platform. What this thing needs is a truly multidisciplinary effort to expeditiously solve this thing, forever. And we need to build on existing dynamics not to loose valuable time. We have been waiting for a solution for too many years.
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Postby jimmylegs » Tue Jan 18, 2011 10:10 am

i started writing this in response to the topic under CCSVI but have posted it here instead - sorry in advance for any non sequiturs as a result.

Okay, so, one potential cause of hypoglycemia: suboptimal trivalent chromium status.

LITERATURE
excerpts from a google scholar search on the terms hyperinsulinemia, chromium:

http://scholar.google.ca/scholar?hl=en& ... =&as_vis=0

Chromium supplementation for women with gestational diabetes mellitus
L Jovanovic, M Gutierrez… - The Journal of Trace …, 1999

Effect of chromium chloride supplementation on glucose tolerance and serum lipids including high-density lipoprotein of adult men
R Riales… - American Journal of Clinical Nutrition, 1981

Chromium action and glucose homeostasis
BW Morris - The Journal of Trace Elements in Experimental …, 1999 -

Chromium improves insulin response to glucose in rats
JS Striffler, JS Law, MM Polansky, SJ Bhathena… - Metabolism, 1995

and, an interesting abstract:
http://www.springerlink.com/content/u07857312h586124/
Chromium deficiency after long-term total parenteral nutrition
A 63-year-old female developed unexplained hyperglycemia and glycosuria during administration of a total parenteral nutrition regimen on which she had been stable for several months. Because the patient had no history of diabetes or evidence of an infection, chromium deficiency was considered. Plasma chromium level was 0.1 g/dl (laboratory reference interval: 1.8–3.8 g/dl). Fourteen days of supplemental intravenous chromium chloride (200 g/day) allowed complete withdrawal of exogenous insulin with no further hyperglycemia or glycosuria. Correction of unexplained glucose intolerance following vigorous chromium supplementation indicates that the patient had chromium deficiency. Subsequent plasma chromium levels remained unchanged, possibly reflecting the sensitivity limits of the assay that was used, the uncertainty that exists regarding appropriate reference intervals for this element, and the fact that plasma levels do not always correlate with total body stores.


on the other hand... keeping in mind that chromium chloride is relatively poorly absorbed...:
The effects of chromium supplementation on serum glucose and lipids in patients with and without non-insulin-dependent diabetes
Abstract
Seventy-six patients with established atherosclerotic disease were treated daily with either 250 μg of chromium orally as chromium chloride or a placebo for a period of 7 to 16 months (mean, 11.1 months). Serum chromium increased from 2.69 ± 0.09 to 12.12 ± 0.77 nmol/L (mean ± SE, P < .005). Serum triglycerides were lower (1.68 ± 0.11 and 2.10 ± 0.14 mmol/L, respectively; P < .02) in the chromium-treated patients than in the patients who received placebo, and serum high-density lipoprotein (HDL) increased (from 0.94 ± 0.05 to 1.14 ± 0.07 mmol/L, P < .005) in the patients who received chromium. There was no change in serum cholesterol or blood glucose during the study.


Chromium picolinate increases membrane fluidity and rate of insulin internalization
Abstract
The effects of chromium chloride, chromium nicotinate, and chromium picolinate on insulin internalization in cultured rat skeletal muscle cells was examined. Insulin internalization was markedly increased in cells cultured in a medium that contained chromium picolinate and the increased internalization rate was accompanied by a marked increase in the uptake of both glucose and leucine. The effect was specific for chromium picolinate since neither zinc picolinate nor any of the other forms of chromium tested was effective. The increased insulin internalization rate may result from an increase in membrane fluidity since chromium picolinate and to a lesser extent, chromium nicotinate, increased the membrane fluidity of synthetic liposomal membranes


Effect of Chromium Supplementation on Glucose Metabolism and Lipids
http://care.diabetesjournals.org/content/30/8/2154.full
No significant effect of chromium on lipid or glucose metabolism was found in people without diabetes. Chromium supplementation significantly improved glycemia among patients with diabetes. However, future studies that address the limitations in the current evidence are needed before definitive claims can be made about the effect of chromium supplementation.


REVIEW ARTICLE
Chromium Research from a Distance: From 1959 to 1980
Walter Mertz, MD
http://www.jacn.org/cgi/reprint/17/6/544.pdf (full text)
Key teaching points:
• Chromium is recognized as an essential element.
• Chromium potentiates insulin action.
• A major challenge in chromium research is the development of practical methods for diagnosing chromium deficiency.


TESTING
http://www.muschealth.com/lab/content.aspx?id=150241

Chromium measurement

What is this test?
This test measures the amount of chromium in blood. It is used to evaluate and manage chromium exposure or poisoning, and chromium deficiency.

What are related tests?
-Chromium measurement, urine
-Glucose tolerance test
-Insulin measurement

SUPPLEMENTATION
A study. regrettably small n. but a starting point:

Effects of supplemental chromium on patients with symptoms of reactive hypoglycemia.
Anderson RA, Polansky MM, Bryden NA, Bhathena SJ, Canary JJ.
Metabolism. 1987 Apr;36(4):351-5.
Abstract
"To determine if chromium (Cr) is involved in hypoglycemia, eight female patients with symptoms of hypoglycemia were supplemented with 200 micrograms of Cr as chromic chloride for three months in a double-blind crossover experimental design study. Chromium supplementation alleviated the hypoglycemic symptoms and significantly raised the minimum serum glucose values observed two to four hours following a glucose load. Insulin binding to red blood cells and insulin receptor number also improved significantly during Cr supplementation. These data suggest that impaired Cr nutrition and/or metabolism may be a factor in the etiology of hypoglycemia."

Chromium treatment does not appear to affect glucose levels in kwarshiokor, a protein-energy deficiency disease in which, in this study at least, the patients had 'normal' chromium levels:

Chromium(III) in Hypoglycemia and in Impaired Glucose Utilization in Kwashiorkor
http://www.ajcn.org/content/21/3/195.abstract
"...The diabetic glucose tolerance curves returned to normal following treatment with a high-protein, high caloric diet for 1-2 weeks. Chromium deficiency did not appear to be responsible for the rapidly reversible impaired glucose utilization seen in patients with kwashiorkor in Cairo, Egypt, United Arab Republic."

Therefore, it would seem a chromium test would be useful before deciding whether chromium might be implicated in a particular individual's hypoglycemia.

OPTIMAL CHROMIUM VALUES
Biological Trace Element Research
Volume 79, Number 3, 205-219, DOI: 10.1385/BTER:79:3:205
Concentrations of seven trace elements in different hematological matrices in patients with type 2 diabetes as compared to healthy controls
"This study aimed to compare the trace element status of patients with type 2 diabetes (n=53) with those of nondiabetic healthy controls (n=50). The concentrations of seven trace elements were determined in the whole blood, blood plasma, erythrocytes, and lymphocytes of the study subjects. Vanadium and iron levels in lymphocytes were significantly higher in diabetic patients as compared to controls (p<0.05 for iron and p<0.01 for vanadium). In contrast, lower manganese (p<0.01) and selenium (p<0.01) concentrations were detected in lymphocytes derived from patients with type 2 diabetes versus healthy subjects. Furthermore, significantly lower chromium levels (p<0.05) were found in the plasma of diabetic individuals as compared to controls. Trace element concentrations were not dependent on the degree of glucose control as determined by correlation analysis between HBA1c versus metal levels in the four blood fractions. In summary, this study primarily demonstrated that trace element levels in lymphocytes of patients with type 2 diabetes could deviate significantly from controls, whereas, in general, no considerable differences could be found when comparing the other fractions between both patient groups. Therefore, it seems reasonable to analyze metal levels in leukocytes to determine trace element status in patients with type 2 diabetes and perhaps in other diseases."

Ooh.. here's one with values/units!:

"Our results indicate that the chromium concentration ranges of serum and urine for diabetics are 0.22–0.36 and 4.54–5.90 μg/L, respectively, significantly lower than 0.66–0.84 and 7.80–9.68 μg/L for the normal (P<0.001), which implies that the elderly diabetics probably lack chromium."

So, these patients had a third of the chromium in their systems compared to healthy controls? Yikes.

Too bad I can't find anything on chromium levels in MS patients... grr.

FOOD SOURCES

http://www.whfoods.com/genpage.php?tnam ... nt&dbid=51
"Romaine lettuce is an excellent source of chromium while onions and tomatoes are very good sources of this mineral. Other food sources of chromium include brewer's yeast, oysters, liver, whole grains, bran cereals, and potatoes. Many people do not get enough chromium in their diet due to food processing methods that remove the naturally occuring chromium in commonly consumed foods."

Hope that sheds a bit of extra light.

PS ON SUGAR CRAVINGS
Long-term safety evaluation of a novel oxygen-coordinated niacin-bound chromium (III) complexM Shara, AE Kincaid, AL Limpach… - Journal of inorganic …, 2007
http://www.ncbi.nlm.nih.gov/pubmed/17555823
"... A significant volume of research studies have demonstrated that chromium (III) complexes play a significant role in regulating appetite, reducing sugar cravings and increasing lean body mass."
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Postby lyndacarol » Tue Jan 18, 2011 7:36 pm

JL – good information. I thought I had read somewhere some time ago that peanuts were a good source of chromium so I was surprised NOT to find it listed in the information. I don't think I'll give them up (I like peanuts.), but I will add more romaine lettuce to my diet. Thanks for the info.
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Postby jimmylegs » Tue Jan 18, 2011 8:19 pm

np LC :)

i can't find info on the amount of chromium in peanuts. the food source info above comes from 'world's healthiest foods' web site so maybe they don't consider peanuts the healthiest choice compared to lettuce, tomato and onion?

also on the detailed peanut info page at nutritiondata.com, there is nothing on chromium content:
http://nutritiondata.self.com/facts/leg ... cts/4357/2

i have seen 'nuts' mentioned generically as sources of chromium but the actual sources seem to be brazil nuts and hazelnuts.

so looks like, enjoy the peanuts lol just don't rely on them, not for chromium anyway!

couple more tidbits:

"Chromium Foods
The Institute of Medicine recommends a daily intake of 25 to 45 mcg for adolescents and adults. Meeting these recommendations is relatively easy when eating an overall balanced diet. Romaine lettuce, an excellent source of chromium, contains 16 mcg per two cups. Onions contain 25 mcg per cup and tomatoes contain 9 mcg of chromium; both are very good sources of chromium."
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Postby Leonard » Wed Jan 19, 2011 8:50 am

MS Made Simple:

Many years before we get to see symptoms of MS, a process has already started inside our body caused by under-nourished myelin and neurons. However we do not notice it yet. The cause is vein constriction in the neck (causing a poor circulation of blood through the cerebro-spinal, origin from birth) and on top of that the formation of iron depositions in the draining veins (which will make glucose transport across that part of the blood brain barrier more difficult).

For some people then who already have a low glucose condition (due to the venous strictures but no MS), by mid age insulin resistance will develop and this will further deteriorate glucose transport (the second peak in the age of onset).

Initially, under-nourished neurons will go in sleep mode. If there is serious malnutrition, the myelin and neurons will die. Microglia then clean up the mess. T-cells can not enter through the BBB. At the time that microglia come out, T cells jump on them and do their job.

If after years that process has advanced sufficiently, we see inflammation of the BBB and eventually scars. And a little later one is diagnosed with MS typically when the neurological symptoms start to occur.

Nothing autoimmune therefore, the T cells are just doing their job.

People with MS generally have need for sugar, also have high glucose in their blood in an attempt to meet the needs of the hungry brain. But over time this also attracts a greater insulin resistance, so when that happens, the high consumption of sugar starts to work counterproductive and the situation will deteriorate further.

what to do:
1. ensure the veins are open to ensure a good blood flow and possibly that the iron depositions are taken away.
2. bring the blood sugar back to normal and if necessary take medication to overcome the insulin resistance (step 2 especially important for those people diagnosed after 35; to note as well that due to the high sugar consumption in our modern society increasingly young people develop insulin resistance)

For myself, I am sure that this MS. And also that this line of thought will prevail.
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Postby Leonard » Fri Jan 21, 2011 6:36 am

here is further evidence for the low-glucose hypothesis: http://www.ncbi.nlm.nih.gov/pubmed/12938635

ccsvi is part, in fact it causes a low glucose condition that sets off a whole cascade of events with MS as the final neurological outcome.
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