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As Leonard and lynda-carol have been doing, looking into insulin resistance and the role of glucose fits well with CCSVI too if it's true that the refluxing blood has not just less oxygen but also less glucose to meet the needs of the very hungry brain.

If the blood is slow getting through the brain it stands to reason that it not only gets very very low on oxygen but glucose as well by the time it gets back into the heart.

Might go towards explaining why exercise makes such a difference. The faster pumping heart will at least mix the overused venous blood faster with blood that isn't so exhausted, and maybe increase arterial pressure towards the brain.

The cognitive problems and fatigue might have something to do with bad brain nutrition. Not to mention atrophy and cell death (brain starvation?).

@1eye: thank you, this is yet another piece of the puzzle! It may help explain why the drainage side of the brain is more affected. Clearly the iron depositions on the drainage side is one thing, it will be a fact that the oxygen/glucose level in the blood will be poorest on the drainage side as well further weakening the already low glucose condition of that part of the brain.

And exercise may help, for the reasons you mention. I think many MS patients may confirm this including myself, but at the same time it should not be too much exercise either because then the glucose build-up in the cells (or in any case what is left of that) will be used up...

the low-glucose hypothesis goes beyond plausibility!

The article from the Medical Director of the National Multiple Sclerosis Society of Australia from 2006 states:
.... there are two peaks on the age of onset graph at 25-30 and 40-45. This is presumably due to a small number in the intermediate age group 35-40. Since this statistic has not previously been reported, it may simply reflect some non-random feature in the case selection process.

http://newsgroups.derkeiler.com/Archive ... 01256.html

I have seen the observation that there are two peaks in the age of onset graph before; there must be more evidence because I have seen it! The explanation given however "This is presumably due to a ... etc " is not correct. There actually is a double peak.

Why? How is this double peak explained? Young people who get MS have serious stenoses and get MS onset already by 25-30 years of age. Others who have stenoses but less severe do have a low glucose condition of their brain but not enough to suffer from MS yet. At mid age (around 40) when the insulin resistance start to develop in about 8% of the general population, this will affect these "stenosed patients". Because these people already have a fairly weak glucose condition, they will detoriate further quickly and MS will show up.

The explanation is as simple as it is beautiful and it confirms the picture that MS is the result of a low-glucose condition of the brain. It also confirms the picture found by Zivadinov and others that stenoses are not confined to MS patients only but that they occur more frequently in the general population.

If you have these stenoses, and you are among the 8% of the population which develops insulin resistance (where there may clearly be a genetic predisposition), you may get MS, just like me. I had the stenoses in the left and right IJV and in the Azygos, and I had onset at 47 years of age, and my farther has diabetes 2 just like his mother..

I believe there is no way around this concept. The double peak is not fake, it is not invented, it is real and explained by the ccsvi - low glucose/insulin concept.

I start to believe that the detoriation of the glucose transport at mid age is caused by a calcification of the veins and not primarily due to increased insulin resistance.

I am convinced that the double peak in the graph of MS onset is explained by:
1. at young age (first peak in graph of age of onset 25-30): by iron deposits on the vessel wall and an insufficient blood flow for a good supply of glucose.
2. at middle age (second peak in graph of age of onset 40-45), patients who already have a low glucose condition in their brains will now be affected by the normal process of atherosclerosis (of the veins). Years later they may develop diabetes, possibly due to increased insulin resistance also caused by the same atherosclerosis. This also explains the prevalence of diabetes in MS.

In summary, it is the developing atherosclerosis that constitutes the primary process for the detoriation of the glucose supply, not an increased insulin resistance as such.

Whether an early start with the anti-diabetes drug metformin ( http://www.metformine.com/ ) would help is a very interesting question. In any case, my triglyceride levels, and prior to my low fat diet, also my cholesterol were too high. And the risks/side effedts of this drug seem to be very low.

I think the answer to the question about the early start with metformin is very important! But I also sense a reluctance/resistance from medical practitioners that we (as patients) bring new concepts and insights that do not fall within the existing protocols. Like with CCSVI where we saw a huge resistance from the established order (from neurologists), it is not impossible that we will see again a resistance to this new insight from the established order (from endocrinologists/diabetologist).

Last night, I saw an interesting program on the Belgian TV on reserach into Alzheimer that talked about the competition between research teams worldwide over the last 20 years. In our case, we also see a lot of envy and competition. On top of that, we see the traditional vertical silo's of neurologists, vascular experts and endocrinologists, different micro-cosmos's as we saw, each with their own interests, motivations etc.

These vertical silo's have now been replaced by a bigger cloud or clouds of knowledge and ideas that fork into thousands of thin lines and pockets of information that proliferate as far as every remote corner of the world. With a very hungry and motivated public at the other end, that is us, and we are learning fast.

Just like with ccsvi, with the help the Internet and these social fora, this global circulation of ideas and brains will prove to be unstoppable.

leonard, this is all so interesting. and, you explain it so good. i am hopeing as you are that all the different specialists will start to share and work together.

Let's recap the facts and see whether we can find some conclusions:

- there are two peaks in the graph of the age of onset: at 25-30 and at 40-45. Young people who get MS have serious narrowings in the neck veins. The supply of nutrition/glucose will be insufficient because of slow blood flow and iron depositions (mainly on the draining side). At mid age when hardening of arteries and veins occurs (a normal process for every one), those people who have narrowings in the neck veins and already a weak glucose condition of their brain but not yet MS will suffer because the supply of nutrition/glucose will now become insufficient. This explains the double peak in the graph of age of onset. The double peak is mentioned for instance in: http://newsgroups.derkeiler.com/Archive ... 01256.html

- when the supply of glucose gets insufficient, cells will die (including myeline and neurons) and the immune system cleans up the mess. That is when MS shows up. The correlation between MS and a (low) supply of glucose is reported in this originally Russian paper of 2003: http://www.ncbi.nlm.nih.gov/pubmed/12938635

- the relation of MS and Vitamin D is well known. High Vitamin D during the time your mother was pregnant from you and your youth (in the period your cells were growing) reduces the risk for MS. The intra-cellular calcium will be lower if there was a high Vitamin D level; conversely, the intra-cellular calcium will be elevated if there was a lack of Vitamin D. Sustained elevations of intracellular calcium may inhibit insulin-target cells from sensing the brisk intracellular calcium fluxes necessary for insulin action, such as in particular glucose transport. See this recent article in the International Journal of Endocrinology: http://www.hindawi.com/journals/ije/2010/351385.html

- Diabetes 2 (old age diabetes) and MS have very similar symptoms. It is known that in case of diabetes 2, the process of demyelination is already well underway for many years (I found a recent article in a journal with good reputation on the net but I can not find it back now but it is there). The same is true for MS, the process of demyelination started much earlier. Although they are not the same disease, they may well have a common cause i.e. a common underlying metabolic mechanism namely a lack of glucose supply due to the hardening of the arteries and veins, and in fact they may be two sides of the same coin. Diabetes may affect the whole body, in our case the disease is concentrated around the cerebro-spinal. See this link for the remarkable resemblance of effects: http://diabetes.niddk.nih.gov/dm/pubs/neuropathies/ It may also help to explain the prevalence of diabetes in MS. It reports: Several investigators have found some metabolic disorders linking both diseases, such as abnormalities in fat, calcium, and vitamin D metabolism. Also, there is evidence of disruption of myelin due to changes in glucose levels. http://care.diabetesjournals.org/conten ... 984.1.full

If we take all these facts together, and also consider how people who have been liberated from ccsvi recover, the link of MS with the glucose condition of the cerebro-spinal goes beyond doubt.

There is an effective medication for diabetes 2 that is called metformin. It is made from the French lilac, a plant used in folk medicine for several centuries, and it is safe and widely prescribed for diabetes. http://en.wikipedia.org/wiki/Metformin

What is more interesting for us is that the medication has been investigated for other diseases where insulin resistance may be an important factor. Or may be I should write here where glucose transport is an issue. I do therefore not exclude the possibility that metformin will not only help diabetes 2 patients to overcome their insulin resistance, but also that metformin will help improve glucose transport to hungry cells in MS patients in particular at mid age and later when hardening of the veins/calcification becomes a factor. Therefore, besides the opening of narrowed veins by balloon agioplasty, metformin could be a useful medication for us to improve the glucose transport and help overcome MS.

I would be very interested in your views and/or reactions.

Leonard, wouldn't people in the first peak (age 25-30) then get hit harder when their arteries or veins age and interfere even further with the glucose issues?

I think the vitamin D link with intra-cellular calcium and glucose transfer is fascinating, I still need to read up on that.

Diabetes 2 (old age diabetes) and MS have very similar symptoms. It is known that in case of diabetes 2, the process of demyelination is already well underway for many years (I found a recent article in a journal with good reputation on the net but I can not find it back now but it is there).

Very interesting.

Are you or any other MSer thinking of trying Metformin? I am curious if it will work.

That's what I asked in the same post in the general discussion. I wondered if leonard would be trying metformin.

Leonard, very interesting thread. Just to add to this, 50% of people diagnosed with hemochromatosis (iron overload) will have either Type 1 or 2 diabetes.

Case Study: Hemachromatosis in Type 2 Diabetes

Phlebotomy therapy has a variable impact on diabetes control. In a large study exploring the effect of therapy on diabetes control, 40% of 72 patients on insulin or oral agents showed improved glucose control following phlebotomy therapy. This same study reported that 6% of patients were able to stop insulin therapy during phlebotomy therapy, but 12% of the study group required increased medication to achieve good glycemic control. The majority of diabetic patients will experience no change or a progressive worsening in their diabetes management despite phlebotomy treatment.

http://clinical.diabetesjournals.org/co ... 2/101.full

Cece wrote:Leonard, wouldn't people in the first peak (age 25-30) then get hit harder when their arteries or veins age and interfere even further with the glucose issues?

YES, I think this is known by neurologists. Of course it depends on the degree of hardening. If you have diabetes 2 in the family, clearly there is a genetic predisposition and you should be alerted.

Cece wrote: I think the vitamin D link with intra-cellular calcium and glucose transfer is fascinating, I still need to read up on that.

YES, it is fascinating isn't it and -besides the double peak in the graph of age of onset- a centre piece in the thesis. No one will be able to get around it

Cece wrote: Are you or any other MSer thinking of trying Metformin? I am curious if it will work.

YES, and I am sure that it will work. My father had weakening of his legs when he was around 58 years old. He never had MS though, but may have some venous problems. He was diagnosed with diabetes 2 at more or less the same time. We are now 25 years later, he is 83 years old and in good health. The weakening seems to have evaporated... But he takes Metformin... already for 25 years...

My blood sugar and my fast serum insulin response under stress were tested last week. Things were normal or a sort of normal. So from the diabetics side, I am OK, at least up till now. But I have another problem (=MS) and the medical protocols of endocrinologists do not say anything about that... So the doctor can not prescribe...

What is happening here has never been seen before. We go at the speed of light, the medical system goes at glacial speed, or at best the speed of a plane. We have a global college and brains circulating, they have at best pockets of information that they may share at conferences, meetings, .. When we share information, it is "us for us", in their world there is a lot of envy and competition (not in the least for the intellectual property). We are motivated by our own health situation (which is even more powerful than the $) and we are experienced (we know what it is and what the symptoms are from the inside), they may have different motivations, experiences and expectations. And -in all fairness-, we have the freedom to think and express ourselves (which we do), for them that may be different ("primum non nocere").

We are witnessing an intellectual transformation here that is more sweeping than anything we have seen in the past. The technological revolution of the Internet and these social fora provide extraordinary tools for searching, ordering and processing information. The monopoly of information enjoyed by the medical sector or its various disciplines disintegrates. This makes that we are light-years ahead (and some doctors have literally told me precisely this).

The systemic problem is one of cultural preparation, the challenge is to graduate the computer age. That may be an issue that transcends the medical sector. And perhaps here lies a role for governments.

http://answers.yahoo.com/question/index ... 418AAgemEf

Curious what you think of these natural alternatives to metformin. Or if jimmylegs reads this.

In the posting above, I suggested that Metformin could help us to overcome MS.

This is a link to a report on the German TV of last Sunday about the possibility that Metformin could be a very effective drug against Alzheimer. And guess what, it would be to improve glucose transport and prevent cells from dying.

http://www.ardmediathek.de/ard/servlet/ ... Id=6360790
The video starts after 15 seconds. May be someone could provide English subtitles. I know that some of you are really good at that.

and the story goes on:

more evidence of the link of MS with diabetes and the possible positive effects of Metformin for treating MS:

http://www.journals.elsevierhealth.com/ ... 5/abstract

http://www.stemnow.com/?p=73
http://www.ncbi.nlm.nih.gov/pubmed/19494326

Potential mechanisms for these effects include insulin's role in cerebral glucose metabolism, peptide regulation, modulation of neurotransmitter levels, and modulation of many aspects of the inflammatory network. An intriguing question is whether insulin abnormalities also influence the pathophysiology of multiple sclerosis (MS),...Ongoing studies will determine whether thiazolidinediones improve cognitive functioning for patients with type 2 diabetes or Alzheimer's disease. Future studies are needed to examine the effects of thiazolidinediones on patients with MS.

Bad news on toxic substances to treat....from Wikipedia for a quick reference.

Chemically, the members of this class are derivatives of the parent compound thiazolidinedione, and include:
Rosiglitazone (Avandia), which was put under selling restrictions in the US and withdrawn from the market in Europe due to an increased risk of cardiovascular events.
Pioglitazone (Actos)
Troglitazone (Rezulin), which was withdrawn from the market due to an increased incidence of drug-induced hepatitis.

Metformin has a much better safety profile.

Abstract
Insulin resistance (reduced ability of insulin to stimulate glucose utilization) is common in North American and Europe, where as many as one third of all older adults suffer from prodromal or clinical type 2 diabetes mellitus. It has long been known that insulin-resistant conditions adversely affect general health status. A growing body of findings suggests that insulin contributes to normal brain functioning and that peripheral insulin abnormalities increase the risk for memory loss and neurodegenerative disorders such as Alzheimer's disease. Potential mechanisms for these effects include insulin's role in cerebral glucose metabolism, peptide regulation, modulation of neurotransmitter levels, and modulation of many aspects of the inflammatory network. An intriguing question is whether insulin abnormalities also influence the pathophysiology of multiple sclerosis (MS), an autoimmune disorder characterized by elevated inflammatory biomarkers, central nervous system white matter lesions, axonal degeneration, and cognitive impairment. MS increases the risk for type 1 diabetes mellitus. Furthermore, the lack of association between MS and type 2 diabetes may suggest that insulin resistance affects patients with MS and the general population at the same alarming rate. Therefore, insulin resistance may exacerbate phenomena that are common to MS and insulin-resistant conditions, such as cognitive impairments and elevated inflammatory responses. Interestingly, the thiazolidinediones, which are used to treat patients with type 2 diabetes, have been proposed as potential therapeutic agents for both Alzheimer's disease and MS. The agents improve insulin sensitivity, reduce hyperinsulinemia, and exert anti-inflammatory actions. Ongoing studies will determine whether thiazolidinediones improve cognitive functioning for patients with type 2 diabetes or Alzheimer's disease. Future studies are needed to examine the effects of thiazolidinediones on patients with MS.

that's a great find, Leonard.