I also believe that it took us a long time to get sick and it does take a long time to get well.
After years of following a basic premise, I admit I have tinkered a little. This has been done as a series of refinements and not by trying to fire random shots at different symptoms. My thinking is spelt out below and I have posted it in this section as it represents my reasoning behind an evolving regimen.
I will try to break this note into several sections and I hope I don’t overcomplicate it. If it is all too hard (or boring) jump to the section called “a quick recap” and go on from there. Hopefully you will see a probable path to MS that at its early stages seems very remote from the commonly held view of an autoimmune disorder.
My personal experience
Firstly, let me say I do have MS and was diagnosed 20 years ago. I know the way you feel when you are diagnosed and how varied the reaction of other people can be. I have known the agony of tight muscles and spasms and what it’s like to read a line of words and not remember what they say when you get to the second line. I know what it’s like to feel devoid of energy as though your body is made of cement and the embarrassment when you are alternately patronised or ignored. I know what it’s like to feel like your neck is made of steel bands but you are being strangled. Above all, I understand what it’s like to feel utterly alone while others discuss you and all you can think is “that’s not me at all”.
I hope I have some good news; despite all that went wrong with me I have recovered. Now, at the age of 56 I was able help a friend close a business recently which required us to count, box and load 40,000 books on to pallets. I worked from 6.30am to 5pm each day for 12 days straight and must have picked up tons of boxes weighing 16 to 17 kilos each. I am an office worker not a labourer. I felt no fatigue or impairment beyond what such a back breaking job creates. If ever there was a test of how well I am this was it. I do not assume my MS is cured, I just believe I have it completely under control.
To avoid repetition I suggest you look at my old post on page 2 of the regimens section called Avonex and Valtrex. It is a story of exploration not one of a conclusion. There are obviously some erroneous ideas included in it but I must have been on the right path. Most of us take a walk into a black hole with no torch to guide us or any sign of a light in the distance. We just stumble along. The note below may help you walk the through the black hole.
As I said earlier, it took us a long time to get sick. I suspect the first place to start looking for a beginning is the time when we are being nurtured in the womb. At this stage we are clearly not mature and if the mother does not or cannot feed us correctly then certain aspects of growth will be compromised. Do not blame your mother for this, she may have been carrying a susceptibility passed to her by her mother. It is not the cause of MS but it probably plays a role. This may be a genetic issue but, these days, I doubt it.
When we are neonates our adrenal system is not mature. To quote from Pub Med; “The adrenal gland is part of the endocrine system and produces hormones that are essential for survival. The adrenal cortex, the largest part of the adrenal gland, produces three major hormones. Glucocorticoids regulate metabolism of glucose, protein, and fat and allow the body to respond to stress by increasing blood glucose levels and cardiac output. Mineralocorticoids regulate fluid and electrolyte balance and help maintain blood pressure”.
“The human kidney displays a tubular immaturity at birth, with sodium waste, responsible for a negative sodium balance, and an impaired ability to reabsorb water. In the neonatal period, the human kidney is characterized by an impaired ability to regulate water and sodium homeostasis, resembling partial aldosterone resistance”.
This is an excellent summary – ( http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919537/ ).
If the Adrenals are impaired then so will be the production of aldosterone, a mineralocorticoid or steroid hormone, synthesized in the zona glomerulosa of the adrenal gland which regulates sodium conservation, potassium secretion, and water retention.
Importantly, two receptors, Megalin and Cubilin, play a profound role in a healthy renal system. Something we may not have operating correctly at the right time in development.
To quote from this article – (http://ndt.oxfordjournals.org/content/17/11/1867.full )
“Under physiological conditions, the renal tubular clearance of protein appears to be very efficient.”
“Within the last few years, two endocytic receptors, megalin and cubilin, have been shown to be extremely important for this process. The two multi-ligand receptors are strongly expressed in the apical part of epithelial cells in the renal proximal tubule”.
“While megalin is expressed in many epithelial cells, it appears at present that the expression of cubilin is more restricted”.
“It is most likely that megalin can both bind and internalize its ligands, whereas the cubilin–ligand complexes need megalin to be internalized. The ligand binding is Ca2+ (calcium) dependent. The binding affinity varies considerably from one ligand to another and it is likely that the efficiency of the overall process is related to the high expression levels of megalin and cubilin in the proximal tubule, which thus constitutes a high capacity system. Some of the ligands attract special attention such as the vitamin-carrier proteins and transferrin. Thus, it has been demonstrated that the megalin cubilin-mediated reabsorption of vitamin D binding protein is responsible for the renal conversion of 25(OH)D3 to 1,25(OH)2 D3 in the proximal tubule. For transcobalamin (TC) and retinol-binding protein (RBP), the reabsorption appears to preserve vitamin B12 and vitamin A , respectively, for the organism. Likewise, iron is being captured by the cubilin (megalin)-mediated reabsorption of transferrin and haemoglobin, a process which under pathological conditions with increased glomerular filtration may be harmful to the kidney. It has been proposed that megalin, which binds calcium strongly , could act as a calcium sensor in the parathyroids. It may also be involved in the transport processing of thyroid hormones. Cubilin and megalin bind lipoproteins HDL and LDL, respectively but their role in cholesterol metabolism is not firmly established”.
This shows clearly that, from an early phase, the functioning of Vitamin D, Vitamin B12 and Vitamin A are intrinsically bound to renal tubular function as is calcium, iron, the lipids and the clearance of protein.
If all these contributors to normal healthy function are disturbed because Megalin and Cubilin are malfunctioning in the renal system it should be no great surprise that a precondition for poor health exists. It may be that we have a mutant form of Megalin or Cubilin or it could simply be a timing issue in the path to maturity. We do not know. Similarly, we do not know if this is a genetic malfunction or an environmental consequence that may involve introduced pathogens.
The adrenals also play a role in the synthesis of arginine.
I have selected a few quotes from an article called “Argininosuccinate synthase: at the center of arginine metabolism” from the International Journal of Biochemical Molecular Biology see- ( http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074183/ )
Mammals at the newborn stage use their intestines to produce a product called argininosuccinate synthase. This is necessary as the mother’s milk is naturally low in arginine, a non-essential amino acid.
Producing argininosuccinate synthase from the fetal intestine allows the baby to produce arginine.
“At about two to three years of age, the intestine loses the ability to synthesize arginine as a consequence of the loss of argininosuccinate synthase expression. Subsequently, endogenous arginine biosynthesis becomes an inter-organ process, where the net production of citrulline occurs almost exclusively in the enterocytes of the small intestine and absorption of citrulline from circulation takes place essentially in the cortex of the kidney where it is converted to arginine”.
“Arginine is required by all tissues in the human body for protein synthesis, and by some tissues for specialized needs”. “There are five major pathways in which argininosuccinate synthase plays a key role. These are (a) urea synthesis, (b) nitric oxide synthesis, (c) polyamine synthesis, (d) creatine synthesis, and (e) the de novo synthesis of arginine to maintain serum levels”.
“Arginase splits the arginine to ornithine and urea, which ensures that the arginine generated by the actions of argininosuccinate synthase and argininosuccinate lyase is, for the most part, directed to urea production. Urea is excreted and the ornithine is transported back into the mitochondria to complete the cycle”.
“Argininosuccinate lyase catalyzes the cleavage of argininosuccinate to produce arginine and fumarate". (NOTE-*Fumarate esters are the basis of a recent treatment for MS.)
Argininosuccinate synthase is also involved in nitric oxide metabolism. “Endothelial nitric oxide synthase (eNOS) utilizes L-arginine as the principal substrate, converting it to L-citrulline and nitric oxide. L-citrulline is recycled to L-arginine by two enzymes, argininosuccinate synthase and argininosuccinate lyase, providing the essential arginine for nitric oxide production in endothelial cells . Together, the three enzymes, eNOS, argininosuccinate synthase and argininosuccinate lyase, make up the citrulline- nitric oxide cycle”.
“In adults, the majority of endogenous arginine synthesis involves the intestinal/renal axis. Citrulline is released by the intestines followed by uptake in the kidney. In the kidneys, expression of argininosuccinate synthase and argininosuccinate lyase then promotes conversion of citrulline to arginine and its subsequent release into plasma “.
Conclusion- As we can see, in a healthy system, which matures, the expression of arginiosuccinate synthase switches from dominance by the intestines to the renal/kidney system. If this latter system fails to operate efficiently the cycle is disrupted and the body will make a compensating response. It is this response that matters. Let us not fret about this but simply accept that the healthy path to maturity is not operating as it should and is awry at an important stage of development.
In a healthy renal system we make symmetric dimethylarginine. When the renal system is faulty we make asymmetric dimethylarginine (ADMA). Asymmetric dimethylarginine (ADMA) is a competitive endogenous inhibitor of all Nitric Oxide Synthase isoforms and has been demonstrated to inhibit Nitric Oxide formation and increase oxidative stress in vascular endothelial and smooth muscle cells.
The body needs Nitric Oxide to function and if certain cells fail to produce Endothelial Nitric Oxide Synthase (eNOS) to synthesise Nitric Oxide the body will behave as if it were wounded and produce inducible Nitric Oxide Synthase (iNOS) as a response. Whilst ADMA will also inhibit the ability of iNOS to make Nitric Oxide it will have a profound impact on eNOS leaving iNOS as the most likely form of Nitric Oxide Synthase to persist.
It is the overexpression of iNOS, most probably caused by a failure of the intestinal/renal axis that presents the first step of our path to MS.
A very good description of the differences can between iNOS and eNOS can be found here - http://cardiovascres.oxfordjournals.org ... 3/521.long
To quote Smith and Lassman 2002 (http://www.thelancet.com/journals/laneu ... S1474-4422(02%2900102-3/abstract (you need to buy it)) “Nitric oxide is a free radical found at higher than normal concentrations within inflammatory multiple sclerosis lesions. These high concentrations are due to the appearance of the inducible form of nitric oxide synthase (iNOS) in cells such as macrophages and astrocytes. Indeed, the concentrations of markers of NO production (eg, nitrate and nitrite) are raised in the CSF, blood, and urine of patients with MS”.
Conclusion - The failure of the renal system leads to the overproduction of iNOS over eNOS and the rise of ADMA. The levels of Nitric Oxide are affected and other radicals such as peroxynitrite can arise. We have seen earlier, a healthy renal system is required to synthesise Megalin and Cubilin and a defect here will lead to the malfunctioning of Vitamin D, Vitamin B12, Vitamin A, calcium transport, iron, the lipids and the clearance of protein.
It is important to remember that this step, by itself, does not imply MS but many diseases have symptoms that are common with MS and the imperfect functioning of the renal system and what flows from that suggests many illnesses may share a common origin. (see http://www.biomedcentral.com/1741-7015/11/205 )
It has been known for decades that glyconeogenesis was impaired if vitamin A was deficient (see http://ajcn.nutrition.org/content/9/4/36.abstract).
Despite this, it is very difficult to find good research on Vitamin A. If we return to the neonate stage in our development then we find the focus of articles is somewhat different than the commentary on adults and Vitamin A. (see - http://ajcn.nutrition.org/content/50/3/413.abstract )
To quote, “Retinol stores accumulate in fetal tissue during gestation. Hence, the premature infant faces extrauterine adaptation with less total reserves of retinol than does the term infant. Retinol-binding protein in serum is also lower in the premature infant population. The parenteral retinol supplementation frequently required for these infants has only recently become adequate by the finding of methods to avoid large losses of retinol onto intravenous tubing. Retinol is an essential vitamin for epithelial cell function.”
Whilst we may not be premature babies we may have suffered, like a preterm, from incomplete development in the renal/kidney system, as described above, and our retinol stores may be inadequate. This has significant consequences for the health of the gut.
I quote now from “Cellular Retinoic Acid Bioavailability Determines Epithelial Integrity: Role of Retinoic Acid Receptor Agonists in Colitis” (http://www.ncbi.nlm.nih.gov/pubmed/17035595 )
“Vitamin A is especially critical for gut immunity, and its deficiency results in deregulated production of cytokines such as interferon and impaired antibody responses. Because the intestinal mucosa is an enriched source of cytokines that are secreted from various immunological cell types, the role of the immune system is likely to generate an aggressive physiological response to the imbalance induced by the barrier dysfunction because intestinal epithelial cells interface directly with various potentially harmful antigens”.
“It is therefore noteworthy to expect that high Retinoic Acid bioavailability in the intestinal microenvironment preferentially affects gut epithelium, resulting in a reduced incidence of life-threatening epithelial hyperpermeability of the gut”.
“The effects of endogenous Retinoic Acids are achieved primarily by two types of RA isomers (alltrans Retinoic Acid [atRA] and 9-cis Retinoic Acid [9cRA]), which are synthesized from the retinalaldehyde precursor, a derivative of vitamin A, and are mediated by two classes of nuclear receptors, retinoic acid receptors (RARs) and their heterodimeric counterparts, retinoid X receptors (RXRs). RARs are activated both by atRA and 9cRA, but RXRs are selectively activated by 9cRA. Accumulated evidence supports the possibility that atRA is an obligatory component in the differentiation of epithelial cells that leads to the establishment of epithelial integrity”.
Conclusion Without going into any greater detail on the function of retinoids, it is clear that the absence of sufficient Vitamin A, the precursor of retinoids , will have a profound effect on the epithelium of the gut. As we have seen earlier, a malfunctioning renal complex producing an insufficient supply of megalin and cubilin will be compromised in its ability to process Vitamin A. This would imply a renal malfunction exposes the gut to issues arising from permability.
It is also worth noting that 9 cis retinoic acid, which is derived from Vitamin A, is required to activate the master switch of the thyroid like nuclear receptors called the retinoid X receptor. This receptor can hetrodimerise with the other receptors to form complexes. An example of this would be the RXR/VDR complex. If RXR operates sub optimally then the functioning of the Vitamin D receptors will be compromised.
I will resist making anything but the most superficial comment on Vitamin D. It is far too overhyped for my taste with a somewhat inane emphasis on supplements as an answer. I know this quote is from Wikipedia but it sums it up well enough – (see http://en.wikipedia.org/wiki/Vitamin_D )
Remember, as we have seen earlier, our kidneys/renal system may not be functioning correctly.
“Vitamin D is carried in the bloodstream to the liver, where it is converted into the prohormone calcidiol. Circulating calcidiol may then be converted into calcitriol, the biologically active form of vitamin D, in the kidneys. Following the final converting step in the kidney, calcitriol (the physiologically active form of vitamin D) is released into the circulation. By binding to vitamin D-binding protein (VDBP), a carrier protein in the plasma, calcitriol is transported to various target organs. In addition to the kidneys, calcitriol is also synthesized by monocyte-macrophages in the immune system. When synthesized by monocyte-macrophages, calcitriol acts locally as a cytokine, defending the body against microbial invaders by stimulating the innate immune system.”
“Calcidiol is transported to the proximal tubules of the kidneys, where it is hydroxylated at the 1-α position (lower right of the molecule) to form calcitriol (aka 1,25-dihydroxycholecalciferol and abbreviated to 1,25(OH)2D). This product is a potent ligand of the vitamin D receptor (VDR), which mediates most of the physiological actions of the vitamin. The conversion of calcidiol to calcitriol is catalyzed by the enzyme 25-hydroxyvitamin D3 1-alpha-hydroxylase, the levels of which are increased by parathyroid hormone (and additionally by low calcium or phosphate)”.
If we do not address the capacity of the kidney to convert calcidiol to calcitriol then we are wasting our time. If kidney function is impaired then we need to address the issue of Vitamin D with a reference to what has gone wrong in the renal system. This means looking at the parathyroid function and the possible causes of low calcium or low phosphate as well as the role of megalin and cubilin.
Again, we have not yet arrived at a recognised definition of MS but many of the symptoms would be recognisable. It may be reasonable to assume the precondition for a step down in wellbeing exists due to compromised renal function already described.
Superoxide is a radical. It consists of two molecules of oxygen. We need it to maintain health. The primary function is to kill invading microorganisms. It is biologically very toxic. What happens, however, if we produce too much and how might this occur? In simple terms, superoxide will contribute to the aging of cells, the build-up of hydrogen peroxide in the system, neurodegeneration, cardiomyopathy and lactic acidosis. Fortunately, the body produces various forms of superoxide dismutase to manage this but over time this naturally declines and the subsequent rise in superoxide contributes to our decline with age.
If we have an overabundance of superoxide, beyond anything the body’s natural system can cope with then there is an elevated risk that other reactions may occur. A well observed reaction occurs when Nitric Oxide interacts with Superoxide and the product of this reaction is called Peroxynitrite. Of all the radicals that can arise this is the worst.
How might Superoxide arise in abnormal amounts?
The most satisfactory explanation for the elevation of superoxide above the normal levels is the introduction of an infectious agent that promotes its production. A number of differing infections have been suggested over time but the most likely is Epstein Barr Virus (perhaps better understood as the cause of glandular fever, a common infection in the human population). Another agent may play a role but I will limit this discussion to EBV.
To quote from (http://www.plospathogens.org/article/in ... at.1000492 )
“EBV is a B lymphotropic gammaherpes virus that asymptomatically and persistently infects 90% of humans; it occasionally causes infectious mononucleosis in adolescents and in rare instances is associated with the development of several different types of B cell lymphoma and various epithelial tumours”.
It is not a nice infection but is usually well controlled in healthy individuals. As we seen already there are many metabolical malfunctions already in play when the renal system is compromised so we may not be healthy to begin with.
“EBV establishes lifelong latent infection in the memory B cell pool, and has a strong association with B cell tumours, including post-transplant lymphoproliferative disease, Burkitt’s lymphoma and Hodgkin’s lymphoma. EBV is also present in epithelial cells of oral hairy leukoplakia, undifferentiated nasopharyngeal carcinoma, and some gastric carcinomas, and infection of epithelial cells in asymptomatic persistent EBV infection is thought to be a feature of the normal EBV life-cycle” ( http://www.ncbi.nlm.nih.gov/pubmed/21573183 )
In simple terms; once you are infected by EBV it remains a lifelong infection by binding to the B cells. It is a highly suspicious element as a causative agent in many cancers.
EBV infected B cells are prolific producers of Superoxide
“Epstein-Barr virus (EBV)-transformed cell lines derived from normal B lymphocytes and some B cell lines also possessed cytochrome b558 and two cytosolic proteins. Isolated human peripheral B lymphocytes generated the superoxide anion upon cross-linking of surface antigens such as IgM, IgD, IgG, HLA-DR, and CD19. EBV-transformants derived from normal peripheral B lymphocytes and B lymphoid cell lines also generated the superoxide anion when stimulated with various antibodies against surface antigens. These results indicate that peripheral B lymphocytes have substantial amounts of a superoxide-generating system identical to that in phagocytes and that the system is stimulated to generate the superoxide anion by the cross-linking of clonally expressed surface immunoglobulins or of certain surface antigens”. ( http://www.ncbi.nlm.nih.gov/pubmed/7592536 .)
An EBV infected B cell will be a prolific producer of Superoxide. As we make a new B cell we are actually making a new EBV infected B cell adding to the production of Superoxide as the viral load grows.
As superoxide production grows so will the production of Peroxynitrite and, as we will see, this ultimately places ever greater strain on the ability to make ATP to drive the cellular machinery.
Szabo( http://www.nature.com/nrd/journal/v6/n8 ... d2222.html ) described a number of biological effects of peroxynitrite; antioxidant enzyme inhibition leading to a diminished ability of the cell to protect oxidant and free radical damage, a shift towards a pro-inflammatory phenotype, membrane channel impairment of the calcium pumps by oxidation and nitration causing impaired cellular calcium handling, inhibition of prostaglandin formation and imbalance of the pro and anti-inflammatory mediator pathways. Importantly, he notes the action of Cytosolic enzyme inhibition resulting in the functional impairment of Glyceraldehyde-3-phosphate, a central step in glycolysis and gluconeogenesis.
In a discussion on MS, perhaps nothing is more important than an understanding of the significance of Glyceraldehyde-3-phosphate.
To keep it simple, when we eat food we expect it to helps us make energy. This process involves a critical step using Glyceraldehyde-3-phosphate. Peroxynitrite disables this step.
Each of our cells needs to respire and this involves an exchange of sodium and potassium. The sodium moves out of the cell and the potassium moves in. This happens via a gateway in the cell wall called the sodium potassium pump. The pump does not drive itself, it is influenced by the addition of a phosphate molecule to the pump to open the channel and allow sodium out and potassium in. The phosphate molecule is donated by adenosine triphosphate (ATP). ATP occurs when ADP (adenosine diphosphate) collects a spare phosphate molecule that is floating around and donates it to the pump to swing open the gateway. When the gate has opened the phosphate uncouples from the gateway and ADP tries to collect in again to repeat the process. A good animation that explains this is found here
http://highered.mcgraw-hill.com/sites/0 ... works.html
As you can see, the phosphate is critical to the proper functioning of the pump. The rate at which the exchange of sodium and potassium into and out of the cell occurs is known as the gradient and rate of flow determines the amount of energy created. If the pump operates sub optimally then less energy is created and you will feel weak and fatigued. Additionally, if the pump does not open often enough the cells will become sodium clogged and the exchange of sodium and potassium in and out of the cell will be compromised. Cells will lose viability as the gradient declines. They become engorged and change shape. Blood cells are a good example to look at.
I quote now from Williams Hematology ( http://medtextfree.wordpress.com/2011/1 ... throcytes/
“Although the binding, transport, and delivery of oxygen do not require the expenditure of metabolic energy by the red blood cell, a source of energy is required if the red cell is to perform its function efficiently and to survive in the circulation for its full life span of approximately 120 days. This energy is needed to maintain (1) the iron of hemoglobin in the divalent form, (2) the high potassium and low calcium and sodium levels within the cell against a gradient imposed by the high plasma calcium and sodium and low plasma potassium levels, (3) the sulfhydryl groups of red cell enzymes, hemoglobin, and membranes in the active, reduced form, and (4) the biconcave shape of the cell. If the red cell is deprived of a source of energy, it becomes sodium- and calcium-logged and potassium-depleted, and the red cell shape changes from a biconcave disc to a sphere. Such a cell is quickly removed from the circulation by the filtering action of the spleen and by a perceptive monocyte-macrophage system. Even if it survived, such an energy-deprived cell would gradually turn brown as hemoglobin is oxidized to methemoglobin by the very high concentrations of oxygen within the erythrocyte. The cell would then be unable to perform its function of transporting oxygen and carbon dioxide”
That was just red blood cells. A similar action would occur in any cell if it is deprived of the energy provided by the normal action of the sodium/potassium pump. If Glyceraldehyde-3-phosphate is disabled by peroxynitrite then we are deprived of energy.
Let us recap what is going wrong so far; a malfunction in the renal system means we produce too little megalin and cubilin. As a consequence we are unable to adequately process Vitamin D, Vitamin B12, Vitamin A, calcium transport, iron, the lipids or correctly clear protein. The poor synthesis of Vitamin A into retinoids means little availability of 9–cis retinoic acid to upregulate the retinoid X receptor, the master switch all the thyroid like receptors, including Vitamin D receptors. The lack of megalin and cubilin results in lower conversion of 25(OH)D3 to 1,25(OH)2 D3 in the proximal tubule of the kidney so less Vitamin D is made. Calcium, iron and the management of lipids are also disturbed. The gut wall has become permeable because of the loss of epithelial integrity due to the lack of Vitamin A regulation. The body believes it is damaged and produces iNOS in preference to eNOS negatively impacting on the vasodilating property of the walls of blood vessels. Lastly, the overproduction of Superoxide through the transformation of B cells by EBV infection leads to the production of Peroxynitrite. This potent radical disables a critical step in Glycolysis called Glyceraldehyde-3-phosphate depriving the system of the necessary capacity to produce energy in cells to allow correct respiration and maintain viability. The lack of cell viability impacts on health and particularly impacts on blood cells rendering them disc shaped and gluggy. Little wonder we can become unwell!
This is not yet a definition of MS although so much of what is already going wrong would be recognisable. Ultimately, it is the lesions found scattered throughout the brain and spinal cord, called plaques, where the myelin sheaths that surround and insulate nerve fibres have disintegrated and been replaced by astroglial scar tissue that represents the cardinal pathological feature of the disease.
“The myelin sheath is an extended, modified plasma membrane that is wrapped in a spiral fashion around a portion of an axon. Each myelin sheath is composed of multiple segments of myelin, which are modified extensions of oligodendroglial cell processes. Each oligodendrocyte can contribute myelin to as many as 50 different axons. The sections of myelin are separated from each other by small segments in which the bare axon is exposed to the interstitial space. These segments, called nodes of Ranvier, are the location of multiple sodium channels. When the axon membrane is excited, the generated electrical impulse cannot flow through the high-resistance myelin sheath and therefore flows out through and depolarizes the axonal membrane at the next node, which might be 1 mm or farther away. The low capacitance of the sheath allows depolarization of the remaining membrane between the nodes with little energy and markedly increased speed”. ( http://www.ncbi.nlm.nih.gov/pubmed/10871022 )
Moscarello and colleagues ( http://www.ncbi.nlm.nih.gov/pmc/articles/PMC296292/ ) reported that the normal-appearing white matter of multiple sclerosis patients is unlike the myelin of other people.
“... we have determined that myelin obtained from victims of MS is arrested at the level of the first growth spurt (within the first 6 years of life) and is therefore developmentally immature.... We postulate that this developmentally immature myelin is more susceptible to degradation .... The different techniques, isolation of charge isomers, x-ray diffraction, electron microscopy, and mass spectrometry do not agree on the exact developmental age. However, it must be in the first 6 years of life, i.e., one of the two periods of active myelination (the second active period is during adolescence)”.
Behan and colleagues ( http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1168912/ ), noted a reduced anisotropy in multiple sclerosis myelin- ie water will diffuse more freely across MS myelin than normal myelin. Cell membranes and myelin should normally be natural barriers to limit the diffusion of water across white matters.
Essentially, the Myelin of MS patients remains soft like that of a child up to the first 6 years of development. Not only may our renal system be immature, so is the structure of our MS Myelin. The reason behind this remains unknown but our soft myelin does not require an aggressive autoimmune action to disintegrate. It could be a simple metabolic disturbance such as the sum of all the problems described earlier at work.
Like everyone else, I cannot explain why MS myelin differs from normal myelin. This observation, however, casts great doubt on the autoimmune model as the best explanation of demyelination. It is quite conceivable that the main mouse models of MS are not the most suitable explanation of what is wrong with our myelin and medications based on this approach will ultimately fail because their purpose is narrowly focussed and does not address the many fundamental metabolic failures common in MS patients. These treatments may all do something for some people for some time but without addressing the broader range of fundamental metabolic disturbances then these treatments will ultimately fail the patient. If MS is truly an autoimmune disorder then exacerbations should cease if our immune system collapses such as we see in the case of AIDS. This does not seem to be the case, severely weakening the argument that our problem is autoimmune. See – http://www.rcpe.ac.uk/publications/arti ... _of_MS.pdf
“If MS is an autoimmune disease a particularly informative setting for studying this would be in patients who have MS and are concomitantly infected with HIV infection, a situation which is known to induce a severe state of immune deficiency. Berger et al. reported seven such patients, six of whom developed an immunodeficient state after HIV infection but who continued to have relapsing-remitting MS.... These data would argue strongly against any autoimmune aetiology, i.e. T-cell mediated autoimmune pathogenesis.”
The greatest initial challenge you will have is finding the right advice. All the references I have noted are from the gold standard literature in medical research. The problem is nobody reads it. In the context of what I have described above most neurologists and doctors would seem manifestly unqualified to treat MS based purely on their own failure to read the available literature. Fear of stepping outside the accepted practice, lack of time and perhaps an element of laziness conspire to leave most practioners parroting the same advice. When a senior, learned figure stands up above the crowd and says “I have a better model” in a language they wish to hear then the bulk of the medical community will suddenly adopt the new approach just to stay with the consensus. It has always been this way but I do not see it happening in MS any time soon.
Step 1 – find a doctor with an open mind. The bed side manner is irrelevant. The only question to ask is “is this person making me better?” If the answer is “no”, then move on. Nice people can still hurt you.
What would I attempt to fix first?
Making the giant leap to agreeing with me means you would look at MS as two distinct issues; 1) a series of metabolical problems stemming from a renal impairment and 2) a dastardly infection giving rise to a collapse in cellular viability due to Peroxynitrite poisoning.
Before you can begin to do anything you need to establish a baseline of health.
As the gut has been compromised by poor Vitamin A processing you may be carrying other infections that will complicate any treatment. Fix this first. It is a matter of knowing what you don’t yet know. Get tested for anything a good doctor suspects you may have; look for chlamydia’s, mycoplasmas, rickettisias, Lyme disease, herpes family virus’s, JCV or any other pathogen your doctor suspects. Treat these first as they get in the way of everything else.
Heal the gut. The inadequate processing of Vitamin A and the consequent lack of retinoic acid has left your gut in a vunerable condition.
1) Start drinking a large glass each day of fresh carrot juice. This provides a big dose of Vitamin A in a safe form. You will only absorb as much as you need. Vitamin A tablets are no use and you run the risk of a toxic buildup in the liver.
2) Commence taking the best probiotic you can buy. Ask your pharmacist if there are practioner quality brands behind the counter. The more complex the mix of strains of good bacteria the better. You have to crowd out the pathogens built up over your lifetime. Medications that your doctor prescribes can kill good bacteria in the process so you must supplement with a good probiotic.
Keep taking any prescribed MS medication. (Interferons etc)
If you read my old post (Avonex and Valtrex) you will note I continued to take a standard treatment approach. I don’t for a moment think Avonex really cured me and it was really very difficult to cope with. I did find that in conjunction with another non standard treatment (Valtrex) I got better. All the big name MS treatments have been right through Phase 111 trials and have passed FDA or equivalent approvals. This doesn’t happen unless some benefit was derived. As they are so one dimensional they will not be the answer but persist as best you can as they do something and it is the sum of all treatments that will help. I know how hard this is but do it for now. I have reached the stage where I no longer take Avonex and only rarely use Valtrex for maintenance but it took a decade. A full description is in my old post referred to at the start of this note.
Again, this becomes a choice. Do you attack the formation of Superoxide by attacking EBV or do you try to restore cellular respiration? On balance I would choose the latter but as I had to find my own way I did it the other way around. My thinking is a properly respiring cellular system will make general recovery quicker because energy is restored. I may be wrong but I can’t go back to test this. That’s your job if you wish to try.
To restore proper cell function, take Coenzyeme Q10. This wonderful substance lets ADP pick up a circulating phosphate molecule to make ATP.
Start at 150 mg before bed and increase the dose every second night by that amount. You are feeling your way here but what we are looking for is the night you wake up in the dark feeling ready to start getting up. Maybe you won’t feel this without attacking Peroxynitrite first. If there are no adverse effects gradually increase the dose. 600mg is right for me and I doubt you need any more than that. Remember, it is a potent blood thinner as it will allow blood cells to process sodium and cease being engorged. If you are on a blood thinner, such as Warfarin, check with your doctor as you don’t need to make a chemical blood thinner more potent. (Potentially dangerous).
Start taking a teaspoon of L-Arginine in water each evening. This is enough. This will allows the blood vessels to dilate and helps overcome the renal failure which prevents the formation of Vitamin D and creates gut permeability because Vitamin A is compromised. It will help boost the absorption of B12 and process proteins. You could make this step 1 if you wish depending on so many variables.
(A late edit- Arginine shares a common pathway with Lysine. The Lysine holds many herpes virus in check. Arginine will outcompete Lysine so the viruses get a chance to flare up. You will need a strategy to deal with this. I used Valacyclovir but check with a doctor. It could be a difficult transitional phase)
Commence attacking EBV to lower the viral load. I did this by taking 500mg twice a day of Valacyclovir (Valtrex). I did it every day for 10 years. That is a lot to take but that’s what you need to hit the EBV and keep going. This needs careful monitoring as it is an antiviral and it will attack other similar viruses. The reaction to that can be very difficult to manage. That is why you need a good doctor and the other infections treated first. This could be step 4. I did it as step 2”ish” but some people have an adverse reaction and you may need a doctor’s help.
An alternative to this step is somewhat more risky. As the EBV need the B cell to persist you could use Rituximab (a cancer drug) to blow away the B cells and take Valacyclovir or Gangliovir to finish the job. The risk in taking a monoclonal antibody is it binds to the wrong receptor with deadly consequences (hence get a really good doctor!).
“Thank God”, they cry, “I thought he’d never shut up!”.
None of this is any more than a rough sketch of what I have done. At the outset I mentioned it would take years to get well. I hope something in these notes is of help to you. As we are all at different stages then it cannot be one size fits all. Above all just look, look and look again for any infections. They can compromise everything I have described. Many of you will say what about X or Y. You didn’t mention it. What I have written is sufficient to start. I could talk about Zinc, Magnesium, Iron or other malfunctions such as the behaviour of Insulin but where do you stop. I think I covered the basics of a metabolic disturbance. If some supplements help then use them as the objective is to recover. If I truly believe I have stumbled on another important step in the story I will add to this note.
Do not ever trust the kindly doctor who says nothing can be done. A cold heartless ba*tard may be your best friend if he knows what he is doing. A good doctor understands infection and contraindications, the rest are rubbish. You deserve the best.