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16 Vital Questions about Multiple Sclerosis
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I'm Bob, a health educator from Littleton, CO. Where I'm from is important as you'll soon see. This is an update of an earlier attempt to understand MS from a perspective that seems very logical to me . . . .

Nine-plus years ago my ex-wife was diagnosed with MS and now my girlfriend has found out she has the disease. As I’ve researched Multiple Sclerosis, I came up with several questions that seemed crucial to me. While noticing that most forums and MS sites officially list MS as "autoimmune," my questions don't seem to point in that direction. I welcome any comment or criticism or helpful information from any informed or experienced individuals . . . Thanks.

Sixteen Vital Questions about Multiple Sclerosis:

1. Why does the United States have the highest Multiple Sclerosis rate in the world?

2. Why is Colorado the highest incident U.S. state?

3. Why is Colorado Springs the highest incident large city in the highest incident state?

4. Why do women suffer from MS at a rate of 2-4 times greater than men do?

5. Why is MS less prevalent on the coasts?

6. Why is MS far more prevalent per capita in urban settings than in rural areas?

7. Central Nervous System Dilators pioneered as an MS treatment during the 1950’s by Bayard Horton of the Mayo Clinic were apparently quite successful with few or no side effects in relieving acute attacks promptly and often prevented progression? Why? Why has this specific treatment dropped out of fashion?
8. The prevailing MS hypothesis today is that Multiple Sclerosis is an “autoimmune disease.” That is in some respects many medical researchers and theorists see it has much in common with AIDS, Rheumatoid Arthritis, Lyme Disease etc. As you know there was a time four decades ago when there was only one auto-immune disease; AIDS. Now a look at shows that some 160+ “accepted” and “suspected” autoimmune diseases are now listed including such surprising ailments as narcolepsy and restless leg syndrome. Is it possible that the term “auto-immune” really doesn’t tell us much and we might do better just saying “originating and/or causal factors thus far UNknown?” In any case certainly any single disease on the list (such as MS, for example) might better fit the “originating/causal factors thus far Unknown” category than truly being an auto-immune disease IF auto-immune disease actually exists. Yes, yes we find all sorts of treatments, but no cures for all these ailments labeled “auto-immune,” but perhaps we’d actually cure something if we started out admitting we actually don’t know what causes it? In any case since MS is most prevalent per capita in the United States (Question #1 above) and since “diseases of civilization” such as constipation, obesity, and chronic ailments such as heart disease, stroke, diabetes and cancer are highly prevalent in America might there be something in the lifestyle of the typical American that contributes to these high rates and possibly also to the high American incidence of MS?

9. MRI examinations today frequently depict a lack of correlation between symptoms and lesions in MS (often called the “clinico-radiological paradox). What’s going on? If auto-immune demyelination really is the fundamental essential lesion in multiple sclerosis, why is there often no correlation?

10. Trials of sex hormones show they often improve lesions as well as symptoms and L-arginine, zinc and magnesium supplements also seem to lesson symptoms. Why?

11. What role do deficiencies of endothelial and neuronal nitric oxide and elevated levels of inducible nitric oxide play in MS? Is this symptomatic or causal?

12. Is better detection the only reason MS incidence has risen so dramatically in the last 40 years, or is some (or many) environmental factor(s) exacerbating the situation?

13. What about the “brain leak” theory of MS? Free hemoglobin scavenges nitric oxide avidly, which may create deficiencies especially in the central nervous system, with its greater vasodilator tone. Could depletion of endothelial nitric oxide shift blood from the arterial circulation to the venous circulation in MS sufferers as in diabetics? Could multiple sclerosis result from too little blood in arteries and arterioles leading to vasospastic symptoms? Meanwhile could too much blood in veins and venules lead to blood-brain barrier leakage and lesions?

14. Is there any logical reason for continued loyalty by many to the idea that MS is an anti-immune condition or are we just following the "latest fad?"
15. Recent experiments with flavonoids in the diet of MS patients (and in aging patients without MS) have shown noticeable reduction in MS symptoms (and symptoms of aging) among patients including these nutritious items (blueberries, for example) in their diet. Why? What can we learn from this? How does it tie in with our other discoveries?

16. Is there one over-arching theory that might explain all these factors?


Let us put question #1 aside for now. It’s entirely possible that America has the best MS diagnostic and detection in the world and that’s why we show the highest per capita victimization. Or other factors may be influencing that statistic, for example the world’s highest obesity incidence? An obvious main or, at least, exacerbating factor seems to jump out from questions #2 - #8: OXYGEN! The clearest correlation for Question #2 is that high altitude = lower oxygen levels. Colorado is the state with the highest average altitude among the 50 U.S. states. As far as Question #3, Colorado Springs, the 49th largest city in the country, is easily the highest large metropolitan area in the country roughly 750 ft. (14%) higher than “Mile-High” Denver.

Question #4, Women’s bodies and their unique chemistry may make them far more vulnerable than men to MS for any number of reasons. For now, however, let’s explore the OXYGEN HYPOTHESIS more deeply. Women tend to be smaller and society encourages female physical fitness far less than it does male activity so generally speaking females are less efficient VO max processors than men. Additionally, hemoglobin and iron are more problematical in females during their menses which makes females more likely prey for anemia, again potentially lessening oxygen-use efficiency.

Question #5, the coasts, are by definition, found at sea level hence, lower than 99.999% of the inland areas of the country with more oxygen available. Additionally, coastal diet is far more likely to include fish with its attendant fish oil (deficiencies implicated in Alzheimer’s, high blood pressure and heart attacks) which can aid in oxygen processing.

Question #6, people in rural areas are less likely to face high levels of air pollution (smog) than city dwellers. In particular: diesel fumes, ground level ozone contamination and INHALED nitric oxide contamination are brutal every day facts of life in our largest cities. (By the way: INHALED nitric oxide is confusing in many respects to the layman. A. it is NOT nitrous oxide (laughing gas) once used for anesthetic purposes especially in dentistry. B. Our bodies naturally create nitric oxide and it is one of the most important gases found in our blood stream (as reflected in the Nobel Prize for Medicine awarded to Dr. Louis Ignarro) which we will discuss later as it relates to MS. C. Many people realize that nitric oxide is also an important negative component of tobacco smoke. In any case, the obvious effect of air pollution is less oxygen allowed to reach the lungs, heart, brain and every cell of the human body than one would expect from clear, pure country air.

Question #7, Peter Good’s thought-provoking website has been instrumental in my dealing with these questions. According to him between 1946 and 1959, more than 3000 patients with multiple sclerosis and other demyelinating diseases were treated with the CNS vasodilator histamine diphosphate at the Multiple Sclerosis Clinic of St. Joseph Hospital in Tacoma, Washington. Most of them improved, some quite dramatically. Today’s “fashion” calls for different meds with greater potential for dangerous side effects. CNS vasodilation has largely been dropped despite the fact that it worked. CNS vasodilation with histamine not only consistently relieved a disease now thought to be auto-immune and incurable, it thereby demonstrated that its fundamental lesion may be something entirely different from demyelination.

Peter Good goes on to say that on “March 28, 1996, host Robert Stack of television's Unsolved Mysteries related the story of Mary Clamser of Oklahoma City, a multiple sclerosis patient for 23 years. Mrs. Clamser had relapsing-remitting MS, the most common form among women; her left leg and her bladder were most affected. Each attack lasted no longer than six months, until an attack in 1992 left her unable to walk without assistance.

”On August 17, 1994, a sudden thunderstorm passed over Mrs. Clamser's house. She was in her wheelchair, preparing a bath. As she reached out to turn on the water, a bolt of lightning struck the house. Doctors estimate that at least ten thousand volts of electricity passed through her body. At first she felt "on fire" she said, full of "pins and needles." Then she suddenly realized she could feel her legs again. Since that day, improvement of her multiple sclerosis was rapid. Two years later, she was living a completely normal life. "All symptoms of her multiple sclerosis," said Robert Stack, "are gone."

This is not, of course, the first or only anecdotal report of an affliction reversed by lightning. But the symptoms of multiple sclerosis are believed to be caused by disintegration of the insulating myelin sheaths surrounding nerve fibers in the brain and spinal cord. How a bolt of lightning could restore these insulating layers rapidly--if at all--can hardly be imagined. The obvious implication is that demyelination is not the only cause of multiple sclerosis symptoms.

Something else must be happening in the brain and spinal cord of these persons--something far more reversible than demyelination.” Indeed, my read on Peter Good is that one is left with the very strong impression from Mrs. Clamser’s experience that demyelination is only a symptom and not the cause of MS at all (kind of like finding that cleft palate when operated upon early left a victim who was not a "retarded basket case who would never learn to speak"; and finding that "Mongoloid idiocy" was NOT a NECESSARY part of Mongoloidism but just a nasty side effect related to the victim's inability to process oxygen which, because the brain is the biggest user of oxygen was tragic -- today occasionally a Mongoloid child will be the valedictorian of his/her high school). And as far as CNS vasodilation? Well if it worked, why quit it for other methods with greater attendant side effects? In any case, lightning doesn’t rule out oxygen and dilating blood vessels surely must have as an agreeable side effect: greater oxygen carrying capacity for each cell of the brain, no?

Furthermore, if some “transient reversible factor is a major contributor to MS and is electrical, one clue may be the "night-walker phenomenon" many patients report. Late at night, these patients can get out of their wheelchairs and walk without canes or crutches. One woman nearly blind said she had normal sight every night around midnight. Patients who kept track of these episodes report they feel particularly free when radio static is absent. One Montana man who often drove from city to city late at night said that when he could tune in distant radio stations without static, he could walk for miles down the road. When there was long-distance static, he could "hardly hobble about." Undoubtedly this is some transient factor at work, but not the kind of transient factor neurologists usually associate with this disease.” In other words, MS has not been figured out, so why rule out anything?

Having said that let’s jump ahead to Question #14, Is there any logical reason for continued loyalty by many to the idea that MS is an anti-immune condition? In my humble opinion, AIDS and MS are two diseases that will NEVER be understood until the words “auto-immune” are dropped completely from the physicians’ vocabulary. For the past 50 years medical people have ASSUMED the most complex possible scenario: autoimmunity as the underlying truth about MS without once showing that a simpler cause (suggested by the successes of CNS vasodilators) could be ruled out. As a result we regard MS today as incurable because its primary lesion is thought to be relatively irreversible disintegration of myelin sheaths in the brain and spinal cord.

Neurologists who successfully treated MS with vasodilators thought the lesion was REVERSIBLE because the underlying cause – a diminished blood supply in the brain and cord (leading us to hypothesize an oxygen lack there) was treatable. Because of the autoimmune assumption, workable theories and workable treatments (and cures?) have been relegated to the trash heap.

Question #9, since MRI results seem NOT to show continued and progressive demyelination as the fundamental and unvarying effect of MS and they don’t rule out oxygen as a key factor, we can continue to keep an open mind toward blood and oxygen as the fundamental truth of the disease. Lest anyone decide that I’m seeking oversimplification of a complex problem . . . Siblerud and Kienholz (1994) compared red blood cell concentrations and hemoglobin levels of MS patients who had their mercury amalgam dental fillings removed against blood values of MS patients who retained their amalgam fillings:

MS subjects with amalgams were found to have significantly lower levels of red blood cells, hemoglobin and hematocrit compared to MS subjects with amalgam removal.... The MS amalgam group had significantly higher blood urea nitrogen and lower serum IgG.... A health questionnaire found that MS subjects with amalgams had significantly more (33.7%) exacerbations during the past 12 months compared to the MS volunteers with amalgam removal. Obviously, while we’re still talking about the blood’s ability to deliver oxygen . . . every indication is that a wide variety of toxins and negative effects might stimulate that same over-arching undesirable effect. Indeed, several investigators have preferred psycho-somatic causes as the underlying truth about MS referring to an “MS Personality” created in response to living in a family with a tyrannical father, obliging mother, and atmosphere of strongly emphasized sex taboos and exceedingly great guilt and fear. Perhaps there's a modicum of truth to this, perhaps not. Certainly, physiological causes seem far more likely, but exacerbating psychological contributors should NOT be ruled out. The specific trigger may vary from case to case, but the indications are that oxygen and blood hold the key to understanding MS and a wide-variety of individual susceptibilities may exacerbate the disease’s manifestations, etc.

Let’s talk about autoimmunity more directly. Just as in AIDS, the possibility that the immune system is responding to an agent like a virus is countered by the reality that no such agent has ever been identified nor transmitted to any animal or human. Retrovirus, where art thou????? In truth, endogenous retroviruses have not yet been proven to play any causal role in this disease (MS); and likely never will.

According to PO Behan and A Chaudhuri of Glasgow University, together with BO Roep of Leiden University (2002). The pathogenesis of multiple sclerosis revisited threw down the gauntlet to MS researchers everywhere by contending there is little support for contemporary views that multiple sclerosis is an immunological disease. And not surprisingly, there is little LASTING benefit from treatments based on this misconception and some dangers:

In this review, they suggested that MS is not an autoimmune disease due to its intrinsic clinical, immunological, radiological and histological differences with ADEM [acute disseminated encephalomyelitis] and its experimental model, EAE [experimental allergic encephalomyelitis]. In their opinion, MS has the characteristics of a metabolically determined neurodegenerative disorder with strong genetic influence....

In recent years, most researchers have uncritically accepted the hypothesis that it is an autoimmune disorder, despite this Multiple sclerosis remains a disease of unknown aetiology. An in-depth review of the literature failed to support this concept, and the immunological claims for this disease are tenuous and fragile.... The proposition that MS is a prototype autoimmune disease is weak and open to question: MS is not a model of EAE or, indeed, of any known autoimmune disease. Its histology compares more favorably with other forms of demyelination known to be metabolic in aetiology .... Many scholars of MS in the past have argued strongly that the disease is toxic/metabolic in origin.... Clinical trials are, however, in abundance: a rise from 50 such papers in 1965 to more than 300 by the year 2000. This has been described by some as reflecting 'the sense of excitement in the field of MS therapeutics', but is regarded by us as a sad reflection of the gullibility of researchers in accepting an unproven hypothesis.... The enormous number of trials based on putative immunosuppression and immunoregulatory mechanisms has singularly failed to show a cure or to convey major benefits to MS patients in addition subjecting them to an increased morbidity and mortality.... I have read much of the literature on immune-modifying therapy in MS and it is clear that none of these agents can qualify as a candidate therapy under scrutiny. (Behan et al. 2002)

Question #10, again brings up questions of gender. Women get MS more often and earlier and its path is less likely to be predictable and progressive compared to male victims. Some success has been had treating with either or both male and female hormones. L-arginine creates nitric oxide in the blood which dilates blood vessels. Zinc and magnesium are under-appreciated nutrients which play vital roles in human health. Again, The specific trigger for MS may vary from case to case, but the indications are that oxygen and blood hold the key to understanding MS and certainly there is no outright refutation for that idea to be found in this question.

Question #11 and 13 are best answered and best understood together through the insights of Peter Good: “ Two signs that endothelial nitric oxide may be chronically depleted in multiple sclerosis are that patients tend to be very heat-sensitive, and their platelets are sticky. Sensitivity to stress may reveal depletion of the parasympathetic transmitter neuronal nitric oxide. Other reasons to suspect endothelial nitric oxide depletion in multiple sclerosis are apparent deficiencies of sex hormones, magnesium, and zinc. Estrogen, testosterone via estrogen, and magnesium all utilize endothelial nitric oxide, the primary endogenous vasodilator, to relax vascular smooth muscle. Endothelial and neuronal nitric oxide synthases are zinc enzymes. Another reason to suspect nitric oxide depletion is the likelihood that abnormal red blood cells--large, osmotically fragile, spiny, less deformable, and agglutinated--are hemolyzing in blood vessels. Free hemoglobin scavenges nitric oxide avidly, which may create deficiencies especially in the central nervous system, with its greater vasodilator tone. If depletion of endothelial nitric oxide shifts blood from the arterial circulation to the venous circulation, as it does in diabetics, the most parsimonious explanation of multiple sclerosis might be that too little blood in arteries and arterioles leads to vasospastic symptoms, while too much blood in veins and venules leads to blood-brain barrier leakage and lesions.”

Question #12, is easily dealt with, in principle the last 40 years have seen a precipitous rise in all manner of environmental toxins. Polluted foods (steroids in meats, for example), medical side effects, residential toxins (such as arising from carpet liners, asbestos, etc., etc., ad nauseum), among others all could easily be regarded as potential triggers setting in motion the conditions leading to diminished blood and oxygen to the brain. So while better detection is quite possibly a contributing factor in the high rate of MS in America, modern life hazards (toxins) might also contribute via the oxygen-lack hypothesis we’ve been pursuing. Is this far-fetched? Numerous studies have shown the absolute vital need for oxygen at the cell level. For example many have shown that normal cells deprived of oxygen are far more likely to become cancerous than normal cells in an oxygen-rich environment. Despite all my criticism of auto-immune theories of MS generation, see:
Question #12 and question #15 may be ultimately the same question . . . .
Question #15 Recent experiments with flavonoids in the diet of MS patients (and in aging patients without MS) have shown noticeable reduction in MS symptoms (and symptoms of aging) among patients including these nutritious items (blueberries, for example) in their diet. Why? What can we learn from this? How does it tie in with our other discoveries? Flavonoids reduce inflammation and more importantly reduce brain inflammation. The original purpose of the study linked immediately above was stated thusly: “One of the questions we were interested in is whether something like luteolin, or other bioactive food components, can be used to mitigate age-associated inflammation and therefore improve cognitive function and avoid some of the cognitive deficits that occur in aging,” The study answer seems to be an unmitigated “YES!” as the researchers at the University of Illinois reported that a plant compound found in abundance in celery and green peppers can disrupt a key component of the inflammatory response in the brain. They went on to theorize their findings have serious implications for research on aging and diseases such as Alzheimer’s and multiple sclerosis. Could it be that simple? Good diet and other factors might dramatically reduce brain inflammation and leaks across the blood-brain-barrier thus guaranteeing the brain more usable blood and oxygen and inhibiting problems with free-radicals in the capillaries . . . . who knows?
Questions #1 and #8 might be capable of being tied together: One candidate for lifestyle contributors to MS in the United States might be our overwhelmingly sedentary lifestyle which gives us cardiovascular systems capable only of reduced VO2Max compared to more athletic types practicing intensive aerobic activity on a frequent and regular basis.

Question #16 (Is there one over-arching theory that might explain all these factors?) In answering the previous 15 questions we have laid the groundwork for believing “Perhaps, there is one overarching theory that holds great potential as the candidate that (finally) holds the key to understanding MS: a theory of insufficient blood and oxygen to the brain.

I'd appreciate any informed comments, suggested modifications, etc.


Posted on 11/20/12, 08:49 am
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Reply #1 - 11/20/12  10:31am
" Wow, and I thought I had done a through job in writing a paper while in College about MS. You put everything I have ever read or written to shame.

Your post was was informative and very thought provoking. I hope that the doctors that participate on this forum read your post and chime in with their thoughts and opinions.

Thank you for this information. By the way I also grew up in
Littleton, CO. I now live in Golden.

Marilyn "
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Reply #2 - 11/20/12  9:20pm
" Wow, if you undrstood MS, you would know that most of us dont have concentration to read all that much info. At least me. That post is too long fr me.

But 1st, women get all auto immune diseases more often than men. It would take a scientist to explain that.
Second, in developed countries we are not getting enough vit D bcause we are inside working on computers. Youngest siblings (and only childs) are more likely to get MS b/c we arent exposed to bugs and they found a reason for that. I'm the youngest of 4. We have more toxins in the environment now which is why MS and auto immune diseases are epidemic along w/ cancers in young people like never before. I believe its environmental. I know 4 local women w/ MS and cancer. Go to MS Society website to read all their research.
Sorry about your girlfriend and exwife.
I never lived in CO. I got 1st symptoms of MS in IL on military base. There are a lot of military brats w/ MS and a LOT OF TOXINS ON MILITARY BASES. "
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Reply #3 - 11/21/12  5:24am
" Very interesting info, I do not always process alot of info at once like I used to so - I just go back and read things esp long post with lost of info TWICE or 3 x. I am sorry for the people you have been close to who both have MS, but am glad you hve been in their corner!!! Ellen "
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Reply #4 - 11/21/12  3:02pm
" amazing post, loved it, you brought up so much i have thought about and wondered and some i haven't but now i will reserch the things i dn't put together before. interesting the info on colorado as i lived there 2 or 3 years in the 70's "
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Reply #5 - 11/22/12  12:51am
" Im sure its a good post but I along with many others cant read long posts like this with so much info at once in such a format. Also some of the words were too hard or old fashioned/technical for me to understand.

The questions were good but to me the discussion was too confusing.

I am in Australia & we also have a very high incidence/level of ms & other auto immune diseases too. We have a lot of research too but slower on release of new medications too.

There are more women with ms but there are also a lot of males with it & lack of vitamin d is certainly being brought up a lot as a contributing factor.

Thanks for your post, would love to know where your information came from too. "
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Reply #6 - 11/23/12  4:51pm
" Yes, while thought provoking, a little too hefty to be able to read all the way through. I will say a couple of things. One, I am from VERY RURAL Vermont, which from my understanding is unfortunately the #1 state for MS (according to something I saw posted here recently, Washington State being the next) to address questions 2 & 6. "
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Reply #7 - 11/23/12  8:03pm
" Hi

1¬ when your wife got dx you ran and now ms caught up with you again?

2- my friend got a horrible bacterial infection in a hyperbaric chamber, so I rather live with ms.

3- If you knew something about ms, you would've never posted that and the reasons are too obvious to a person with ms.

4- If you are fishing, you hit the wrong pond. "
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Reply #8 - 11/24/12  5:35am
" As everyone else said it's very long post. very thought provoking.
Basicially to techicial.
Some of what your saying? is they had a treatment in the 40's that worked? And they quit using it? Par for the course,pharm. companies,shut it down.So Dr.s would push medicines they had for kick backs? possible wouldn't be the first time.
Oxygen levels? True Co is the Almost highest evalvations,and the oxygen is thinner.But? wouldn't persons with Resp. problems all over the Usa and other countries? also have low Oxygen levels In there blood?Female verse Male? Hormones play a factor in alot of things. Here is a question that your Dr.s and post didn't come up with,and everyone that has MS and that are here maybe able to chime in here.What about the blood types? such as Rh factor??? How many of you with MS have a RH neg> blood type?
Ok my mind and eyes can't focus on the questions or answers or topic anymore for now. Jan. "

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