This Is MS Multiple Sclerosis Knowledge & Support Community

Hi Annesse,

I don't need convincing about EBV. It's not enough on its own to trigger MS symptoms. Many people live with an infection without any ill effects.

When you looked at Lupus did you look at the fasting amino acid tests to see if the non essential amino acids are low? I think this a marker that needs exploring. The test is as old as the hills but when it's done the doctors tend to just stick it in a file without question.

My arginine levels, in particular, were through the floor when I was unwell. Since supplementing with L-Arginine and taking 450-600mg of Coenzyeme Q10 I have just got better and better and have been able to drop the Avonex and Valtrex which was an unthinkable thin to do a few years ago. I still focus on an anti EBV protocol so I will add Valtrex if I think its required but recently I have switched to Resvesterol which seems to work.

Regards,

Hi Scott~No, I have not looked in detail at the non-essential amino acids in lupus.

Patients with MS do lack CoQ10 though. (I am sure you already know this Scott, but for the sake of anyone who doesn't...)

In the following study the researchers found that patients with MS had significantly reduced levels of CoQ10. Coenzyme Q10 is also known as ubiquinone (UBI).


Oxidative stress in patients with multiple sclerosis.
Syburra C, Passi S


“…In comparison to controls, patients with MS showed significantly reduced levels of plasma UBI …”


Coenzyme Q10 is a fat-soluble compound synthesized by the body and also consumed in the diet. A report from Iowa State University lists beef, chicken, pork, and fish as the foods with the highest levels of CoQ10. Protease would be necessary to release CoQ10 from these high protein foods.

Coenzyme Q10 can also be synthesized by the body, but it requires the presence of one of two amino acids we have found lacking in MS. According to the Linus Pauling Institute’s Micronutrient Information Center at Oregon State University, one of the major steps involved in the biosynthesis of CoQ10 requires either phenylalanine or tyrosine (Higdon, 2003). (Essential amino acids, such as phenylalanine, are derived from foods that contain proteins, and the amino acid tyrosine is derived from the essential amino acid phenylalanine.)


I do issue some warnings in my book on supplementation with amino acids though.

In lupus for instance, the lack of protease and DNase 1 results in not only a deficiency of amino acids and other essential compounds such as vitamin B12, but it also results in undigested protein particles and DNA entering the bloodstream and triggering a massive ongoing immune response. The immune system targets these foreign DNA and protein particles and forms immune complexes. These immune complexes can become lodged in organs and tissues. Here is a picture of one of these immune complexes in a lupus patients bloodstream. Notice the last paragraph where it states lupus patients lack the enzyme DNase 1.

http://www.sciencedaily.com/releases/20 ... 161423.htm

I am going to be providing evidence that this is also taking place in MS.

So, if you are unable to digest proteins and they are triggering an immune response, would it be advisable to take components of those proteins (amino acids) into your body? Would they not also trigger an immune response?

The inability to properly metabolize dietary proteins and amino acids is what led to the unbroken-down bits of protein and DNA in the bloodstreams of lupus patients. The immune system targets these protein fragments and forms immune complexes, which then become lodged in healthy organs and tissues. Taking additional amino acids in supplement form would lead to an increased risk of disease. This is evident in the findings from a study entitled “Intermediary metabolism of phenylalanine and tyrosine in diffuse collagen diseases” (Nishimura, 1959). When lupus patients were given supplements of tyrosine and phenylalanine, the supplements “unfailingly aggravated both clinical signs and laboratory data of collagen disease.”

In celiac disease we know that the immune system is reacting to the "protein" gluten. Would it be advisable for a celiac patient to ingest components of gluten? Would they not also trigger an immune response?

An excess of nitric oxide will react with O2-, a potent free radical, and form “peroxynitrite”. Peroxynitrite is known to damage cells through multiple mechanisms.


In the following study the researchers found that elevated levels of homocysteine (hyerhomcysteinemia) significantly increased nitric oxide production (150% of the control), which then resulted in the formation of peroxynitrite.

Hyperhomcysteinemia activates NF-kappaB and inducible nitric oxide synthase in the kidney.
Zhang F, Siow OK. 2004. Kidney Int. 65(4):1327-38.

“Increased nitric oxide production (150% of the control) resulted in peroxynitrite formation in these kidneys. Hyperhomocysteinemia alone can activate NF-kappaB and hence induce iNOS-mediated nitric oxide production in the kidney leading to increased peroxynitrite formation. This may represent one of the mechanisms for renal dysfunction in hyperhomocysteinemia.”


In the next study the researchers stated that nitric oxide and peroxynitrite have been implicated in the pathogenesis of MS and that they are cytotoxic to oligodendrocytes and neurons.

The potential role of nitric oxide in multiple sclerosis.
Giovannoni G, Heales SJ, Land JM, Thompson EJ. 1998. Mult Scler. 4(3):212-6.


“Nitric oxide (NO) and its reactive derivative peroxynitrite (ONOO-) have been implicated in the pathogenesis of multiple sclerosis (MS). They are cytotoxic to oligodendrocytes and neurons…”


In the following study the researchers concluded that peroxynitrite induced strong primary axonal damage along with severe myelin alteration and demyelination.

In vivo damage of CNS myelin and axons induced by peroxynitrite.
Touil T, Deloire-Grassin MS, Vital C, Petry KG, Brochet B. 2001. Neuroreport.12(16):3637-44.


“…Peroxynitrite induces strong primary axonal damage with characteristics of primary acute axonopathy, together with severe myelin alteration…and demyelination…”



Research has also found the involvement of nitric oxide and peroxynitrite in the pathogenesis of optic neuritis. In the following editorial published in the Journal of Neuro-Opthalmology the authors discussed evidence of nitric oxide and peroxynitrite damage in the loss of myelin proteins and myelin breakdown in optic neuritis.

Nitric Oxide in optic neuritis and multiple sclerosis.
Chuman H. 2006. Journal of Neuro-Ophthalmology. Vol. 26 Issue 2 pp 85-86.

“There has been an explosive growth of research on the role of nitric oxide (NO) in physiological and pathologic processes in the brain. Physiologically, NO functions as a neurotransmitter and a vasodilator for fine local control of cerebral blood flow. In pathologic states, NO is induced in response to various inflammatory conditions. In this issue of the Journal of Neuro-Ophthalmology, Tsoi et al report evidence for inducible nitric oxide synthase (iNOS) and peroxynitrite-mediated damage in optic neuritis (ON)…In the patient with ON, the authors showed localized loss of myelin proteins, myelin breakdown, and the presence of iNOS and nitrotyrosine associated with inflammatory infiltrates on the edges of the nerve and reactive astrocytes. This evidence implicates the role of iNOS in the inflammation and demyelination of ON. Similarly, increased iNOS activity has been demonstrated in astrocytes in demyelinating lesions of postmortem tissues in multiple sclerosis (MS). In addition, a 70% elevation in cerebrospinal nitrite has been reported in living patients with MS…”

Peroxynitrite can be scavenged by “uric acid”, which is the most abundant antioxidant in our blood. However, research shows that patients with MS have significantly lower levels of uric acid, as the following studies confirm. In the first study the researchers concluded that lower uric acid levels in MS patients may represent a primary, constitutive loss of protection against nitric oxide.


Serum uric acid and multiple sclerosis.
Rentzos M, Nikolaou C, Anagnostouli M, Rombos A, Tsakanikas K, Economou M, Dimitrakopoulos A, Karouli M, Vassilopoulos D. 2006. Clin Neurol Neurosurg. 108(6):527-31. Epub 2005 Oct 3.


“Peroxynitrite (PN) has been implicated in multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis…In the overall MS group, patients were found to have significantly lower mean serum uric acid levels…Our findings suggest that lower serum UA levels in MS patients may represent a primary, constitutive loss of protection against nitric oxide…”




In the next study the researchers stated that peroxynitrite exerts a toxic effect on neurons, axons, and glia cells and increases the blood-CNS-barrier permeability and can therefore promote invasion of inflammatory cells into the CNS. On the other hand, uric acid, a peroxynitrite scavenger inhibits blood-CNS-barrier permeability changes, CNS inflammation and tissue damage in experimental allergic encephalomyelitis. The study authors concluded that uric acid levels in MS patients were lower than in controls. In addition, patients with active disease had lower levels than those in remission.



Uric acid and multiple sclerosis.
Mattle HP, Lienert C, Greeve I. 2004. Ther Umsch. 61(9):553-5.


“Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Its etiology is not known, but it is well established that auto-reactive T-cells and monocytes play an important pathogenetic role. Experimental allergic encephalomyelitis (EAE) of mice serves as disease model for MS. In both EAE and MS inflammatory cells produce nitric oxide and its oxidizing congeners such as peroxynitrite. Peroxynitrite and other reactive nitrogen oxide species exert a toxic effect on neurons, axons and glia cells and enhance apoptosis. In addition, they increase the blood-CNS-barrier permeability and can therefore promote invasion of inflammatory cells into the CNS. On the other hand, uric acid, a peroxynitrite scavenger inhibits blood-CNS-barrier permeability changes, CNS inflammation and tissue damage in EAE…Uric acid levels in MS patients are lower than in controls and in patients with active disease lower than in MS patients in remission…At present, uric acid can solely be regarded as a marker of disease activity in MS...”



In the following study the researchers confirmed the role that uric acid plays in scavenging peroxynitrite and the significantly lower levels of uric acid found in patients with MS. In addition, the researchers stated that statistical evaluation of more than 20 million patient records for the incidence of MS and gout, which is caused by high levels of uric acid, revealed that the two diseases are almost mutually exclusive.



Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis.
Hooper DC, Spitsin S, Kean RB, Champion JM, Dickson GM, Chaudhry I, Koprowski H. 1998. Proc Natl Acad Sci USA. 95(2):675-80.


“Uric acid, the naturally occurring product of purine metabolism, is a strong peroxynitrite scavenger…A possible association between multiple sclerosis (MS), the disease on which EAE is modeled, and uric acid is supported by the finding that patients with MS have significantly lower levels of serum uric acid than controls. In addition, statistical evaluation of more than 20 million patient records for the incidence of MS and gout (hyperuricemic) revealed that the two diseases are almost mutually exclusive, raising the possibility that hyperuricemia may protect against MS…”




The significantly lower levels of uric acid found in patients with MS can be clearly explained by a lack of the pancreatic enzyme DNase 1 (deoxyribonuclease). Uric acid is the final breakdown product of dietary DNA. DNase 1 is the enzyme responsible for the breakdown of dietary DNA. An inability to digest dietary DNA, due to a lack of DNase 1, would lead to low levels of uric acid.

Here is a link and some information from a site that explains this quite clearly. I hope the link opens for everyone. It would open on one of my computers, but not on another (something about the browser). Also, there is a really great graph if anyone can figure out how to post it (I tried, really I did).

https://www.inkling.com/read/illustrate ... -of-purine

Degradation of Purine Nucleotides
Degradation of dietary nucleic acids occurs in the small intestine, where a family of pancreatic enzymes hydrolyzes the nucleic acids to nucleotides. Inside the intestinal mucosal cells, purine nucleotides are sequentially degraded by specific enzymes to nucleosides and free bases, with uric acid as the end product of this pathway."

Degradation of dietary nucleic acids in the small intestine
Ribonucleases and deoxyribonucleases, secreted by the pancreas, hydrolyze dietary RNA and DNA primarily to oligonucleotides.Oligonucleotides are further hydrolyzed by pancreatic phosphodiesterases, producing a mixture of 3′- and 5′-mononucleotides. In the intestinal mucosal cells, a family of nucleotidases removes the phosphate groups hydrolytically, releasing nucleosides that are further degraded to free bases. Dietary purine bases are not used to any appreciable extent for the synthesis of tissue nucleic acids. Instead, they are generally converted to uric acid in intestinal mucosal cells. Most of the uric acid enters the blood, and is eventually excreted in the urine.

An excess of nitric oxide can also interfere with the body’s ability to properly regulate the development of new blood vessels (angiogenesis). In the study entitled “Nitric oxide and angiogenesis” the study authors stated, “Elevation of NOS (nitric oxide synthase) activity in correlation with angiogenesis and tumor progression has been extensively reported in experimental and human tumors” (Cooke, 2002).


Nitric oxide regulates a protein called vascular endothelial growth factor (VEGF) that stimulates angiogenesis. Without proper instruction from VEGF, endothelial cells (cells that line the blood vessels) can be stimulated to proliferate and migrate. In addition, long term exposure to VEGF can cause the blood vessels to become hyperpermeable. In the following study the researchers stated that nitric oxide plays a critical role in VEGF-induced angiogenesis and vascular hyperpermeability.


Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability.
Fukumura D, Gohongi T, Kadambi A, Izumi Y, Ang J, Yun CO, Buerk DG, Huang PL, Jain RK. 2001. P Natl Acad Sci. USA 98(5):2604-9.

“Nitric oxide (NO) plays a critical role in vascular endothelial growth factor (VEGF)-induced angiogenesis and vascular hyperpermeability.”



In the following study the researchers stated that the characterization of the active lesions in MS suggests that activated endothelial cells and altered vessel permeability are involved in the pathogenesis of MS and that VEGF was consistently upregulated in both acute and chronic MS plaques.

Vascular endothelial growth factor is expressed in multiple sclerosis plaques and can induce inflammatory lesions in experimental allergic encephalomyelitis rats.
Proescholdt MA, Jacobson S, Tresser N, Oldfield EH, Merrill MJ. 2002. J Neuropathol Exp Neurol. 61(10):914-25.


“The active lesions in multiple sclerosis (MS) are characterized by blood-brain-barrier (BBB) breakdown, upregulation of adhesion molecules on capillary endothelial cells, and perivascular inflammation, suggesting that altered vessel permeability and activated endothelial cells are involved in the pathogenesis of the disease. Vascular endothelial growth factor (VEGF) mediates multiple aspects of blood vessel physiology, including regulation of growth, permeability, and inflammation. To investigate a possible relationship between VEGF expression and CNS autoimmune disease, we examined VEGF expression in MS plaques compared to normal white matter…VEGF expression was consistently upregulated in both acute and chronic MS plaques…These results suggest that overexpression of VEGF may exacerbate the inflammatory response in autoimmune diseases of the CNS by inducing focal BBB breakdown and migration of inflammatory cells into the lesions.”



In the following study the researchers concluded that repeated stimulation with VEGF results in vessel leakiness.


Evidence of angiogenic vessels in Alzheimer's disease.

Desai BS, Schneider JA, Li JL, Carvey PM, Hendey B. 2009. J Neural Transm. 2009 May; 116(5): 587–597.

“…Angiogenic vessels differ from patent vessels in that they have numerous fenestrea, widened inter-endothelial junctions, abnormal endothelial cell shapes, and abnormal basement membranes…Repeated stimulation with VEGF results in vessel leakiness followed by angiogenesis…Furthermore, long-term exposure to VEGF may result in defective vessels; i.e. pathological angiogenesis…Such vascular abnormalities may also contribute to impaired blood flow, reduced nutrient delivery and entry of otherwise restricted infiltrates…”



In our next study the researchers concluded that blood vessels containing proliferating endothelial cells were more pronounced in all MS tissue examined and that their findings suggest that angiogenesis may play a role in lesion progression, failure of repair, and scar formation.

Increased blood vessel density and endothelial cell proliferation in multiple sclerosis cerebral white matter.
Holley JE, Newcombe J, Whatmore JL, Gutowski NJ. 2010. Neurosci Lett. 470(1):65-70. doi: 10.1016/j.neulet.2009.12.059. Epub 2009 Dec 29.




“Multiple sclerosis (MS) is primarily considered an inflammatory demyelinating disease, however the role of vasculature in MS pathogenesis is now receiving much interest. MS lesions often develop along blood vessels and alterations in blood brain barrier structure and function, with associated changes in the basement membrane, are pathological features. The results showed that in all MS samples examined blood vessel density increased compared with controls…Furthermore…we have shown that vessels containing proliferating endothelial cells were more pronounced in all MS tissue examined (normal-appearing white matter, acute, subacute and chronic lesions…) compared with control and this was greatest in the MS normal-appearing white matter…These findings suggest that angiogenesis may play a role in lesion progression, failure of repair and scar formation.”

Hi Annesse,

All good stuff. Can I suggest you have a look at the formation of iNOS vs eNOS, and the role of arginine in endothelial health?

Some of the studies are making eNOS look like a bad guy.

Regards

Scott1 wrote:Hi Annesse,

All good stuff. Can I suggest you have a look at the formation of iNOS vs eNOS, and the role of arginine in endothelial health?

Some of the studies are making eNOS look like a bad guy.

Thank you Scott~

Here is a study that found homocysteine induces endothelial dysfunction via inhibition of arginine transport. The researchers concluded that reduced arginine supply may lead to eNOS uncoupling and generation of superoxide, contributing to HCY-induced oxidative stress.



J Physiol Pharmacol. 2007 Jun;58(2):191-206.
Homocysteine induces endothelial dysfunction via inhibition of arginine transport.
Jin L, Caldwell RB, Li-Masters T, Caldwell RW.
SourceDepartment of Pharmacology and Toxicology, Medical College of Georgia, Augusta, Georgia 30912, USA.

Abstract
Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. High levels of plasma homocysteine (HCY) increase oxidative stress and reduce endothelial-dependent relaxation. We determined whether hyperhomocysteinemia-induced endothelial dysfunction is mediated through inhibition of cellular transport of L-arginine. In endothelial cells, HCY had a biphasic effect on arginine transport. HCY treatment for 6 hr increased L-arginine uptake by 34%; however, uptake was decreased by 25% after 24 h. HCY caused membrane hyperpolarization during both 6 and 24 h incubation periods, indicating that the negative charge facilitating arginine uptake was maintained. HCY significantly reduced expression of cellular arginine transporter protein (CAT-1) after 24 h treatment; whereas endothelial nitric oxide synthase (eNOS) protein levels and basal eNOS activity were not altered. Nevertheless, nitric oxide (NO) formation was significantly decreased. The antioxidant ascorbic acid prevented the effect of HCY on arginine transport. HCY induced formation of the peroxynitrite biomarker nitrotyrosine, which was blocked by supplemental L-arginine. HCY treatment of aortic rings caused decreased vasorelaxation to acetylcholine, which was prevented by supplemental arginine. In conclusion, HCY decreased NO formation and induced endothelial dysfunction without altering protein level or basal activity of eNOS, but through decreases in function and protein expression of the CAT-1 transporter. Reduced arginine supply may lead to eNOS uncoupling and generation of superoxide, contributing to HCY-induced oxidative stress.

Hi Annesse,

So if we go back to your original observation that a lack of B12 correlates with an elevation of Homocysteine then your last post would imply that we should look at whether the level of the non essential amino acid, arginine, also correlates. If it does then it would raise the question "does supplementing with L-Arginine improve B12 and lower Homocysteine?"

Regards

are these enzymes that you can take as a supplement?

Hi Scott~

The problem is with the metabolism of vitamin B12. MS patients are unable to properly "bind and transport" vitamin B12. Protease are responsible for the binding and transport of B12. So, although it is vital to lower homocysteine, I think the best way would be to simply restore the body's ability to properly metabolize vitamin B12. Elevated homocysteine is just one consequence of missing protease and DNase 1. We will be looking at many more. By restoring protease and DNase 1 though a targeted diet, you will be addressing the entire disease process of MS.

I have to say, I am not a fan of isolated nutrient supplementation. Since an estimated 90% of nutrients are as yet undiscovered, and most nutrients are known to act symbiotically with at least 8 other nutrients, the odds of healthfully supplying any nutrient in its necessary component package becomes nearly impossible (Graham, 2008).

Hi jerry~DNase 1 doesn't come in supplement form. It would be quite dangerous to take. I did post some information earlier I think on protease supplements from my fibromyalgia book. Here it is again if you missed it.


"The pancreas releases protease in an “inactive” form due to their strong potential to destroy the cells that produced them and to “digest” other parts of the body, such as the lining of the stomach. To protect the body’s own cells inactive protease are secreted into the digestive tract and only activated when and where they are needed (Powell, 1999).

Research shows that supplementation with protease can destroy the body’s lipases (Layer, 1993). These are the enzymes that digest fats. Supplemental protease can also lead to a serious condition involving damage to the large intestines called fibrosing colonopathy (Bakowski, 1999). In some cases, the problem was linked to the use of high supplemental amounts of enzymes (Milla, 1994). However, the amount of enzymes used has not been linked to the problem in all reports (Jones, 1995).

Our ultimate goal is to restore the health of the entire gastrointestinal (GI) tract in order to properly digest and metabolize proteins. As we have seen, the proper digestion and absorption of proteins requires the functional integrity of the entire gut. If the stomach lining or other parts of the GI tract are further damaged through the use of supplemental enzymes, then we will not be able to achieve our goal.

In addition, as serious a problem as the inability to digest proteins is, it would be equally as serious if the body were not able to digest fats. The destruction of the body’s lipases by supplemental protease could lead to very harmful consequences."

Annesse.

If I cannot bind and transport B12, what steps can I take?

PN

Hi PN~You can replace DNase 1 and protease through a targeted diet. We will be discussing more on this once we get through the disease process. The entire GI tract will need to be addressed. The loss of these enzymes leads to an overgrowth of pathogenic yeasts and bacteria, leaky gut, low stomach acid etc. So, it really is about restoring the health of your entire GI tract. Plus, you don't want to harm or destroy these enzymes in any way, so you would need to avoid things that can do this. For instance, the top 3 drugs that are known to induce lupus-this is called "drug induced lupus"- are all "enzyme" blockers.



More on VEGF..

When blood vessels become hyperpearmeble, substances that should stay inside the blood vessels can leak out and unwanted substances can leak in. One of the substances that can leak out is a blood protein called fibrinogen. In the following study the researchers concluded that increased vascular permeability by VEGF can facilitate leakage of plasma proteins such as fibrinogen.



Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid.
Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. 1983. Science. 219(4587):983-5.

“The original functional discovery of VEGF, which was initially called vascular permeability factor (VPF)… Increased vascular permeability can facilitate leakage of plasma proteins such as fibrinogen, which can then form an extracellular fibrin gel-effectively, a provisional extracellular matrix that promotes development of new blood vessels…”




Here is some additional information on VEGF, fibrinogen, blood vessel hypermeability and angiogenesis. Also, notice the significance these factors have in relation to tumors.

Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis.
Microbiology and Immunology Volume 237, 1999, pp 97-132


"Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) was originally discovered in the late 1970s because of its capacity to increase the permeability of microvessels to plasma and plasma proteins...Using plastic-embedded, light microscopic section and, subsequent, immunohistochemistry, we noted that transplantable tumors growing in guinea pigs and rodents exhibit substantial deposits of fibrin in their stroma. Fibrin results from the clotting of fibrinogen, a 340kDa plasma protein which, under normal circumstances, is retained almost quantitatively within the blood vasculature. For fibrin to be deposited outside of blood vessels in tumor stroma, it was necessary that two requirements be met; namely, (1) that microvessels be abnormally hyperpermeable to permit the escape of fibrinogen and other plasma proteins necessary for blood clotting and (2) that there be a mechanism in place for activating the clotting system. In fact, both requirements were found to be met in tumors. The microvessels supplying tumors were hyperpermeable to fibrinogen and other plasma proteins, and both tumor cells and host stromal cells were capable of initiating extravascular coagulation via the tissue-factor pathway. Encouraged by these findings, we initiated a search for a tumor product that could account for tumor-vessels hyperpermeability. A potent vascular permeabilizing protein was soon found in serum-free tumor culture supernatants…and was subsequently purified to homogeneity and given the name vascular permeability factor (VPF)…”


In the following study the researchers concluded that leakage of the blood protein fibrinogen is a required event for axonal damage in neuroinflammation.

Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation.
Davalos D, Kyu Ryu J, Merlini M, Baeten KM, Le Moan N, Petersen MA, Deerinck TJ, Smirnoff DS, Bedard C, Hakozaki H, Murray SG, Ling JB, Lassman H, Degen JL, Ellisman MH, Akassoglou K. 2012. Nature Communications. Article number: 1227. doi:10.1038/ncomms2230.


“Blood-brain barrier disruption, microglial activation and neurodegeneration are hallmarks of multiple sclerosis. However, the initial triggers that activate innate immune responses and their role in axonal damage remain unknown. Here we show that the blood protein fibrinogen induces rapid microglial responses toward the vasculature and is required for axonal damage in neuroinflammation…Fibrinogen leakage correlates with areas of axonal damage and induces reactive oxygen species release in microglia…Thus, early and progressive perivascular microglial clustering triggered by fibrinogen leakage upon blood-brain barrier disruption contributes to axonal damage in neuroinflammatory disease.”

Hey Pointsnorth,
Still fighting with b12, eh? I lifted this quote from another of annesse's threads dated 2011 (not said by annesse). She has quite a few threads out there. Maybe if you google them you can find some answers more quickly.

http://forums.phoenixrising.me/index.ph ... 904/page-4

Here's another news flash: Lactobacillus plantarum, which has been found to be the dominant bacterial species in sauerkraut (PMID: 17921264), has been shown to be able to produce both folate (PMID: 12902240) and vitamin B12 (PMID: 19953302). Hmmmm.

(Interestingly, l plantarum also kills off segmented filamentous bacteria which are known to up regulate th17)

I've not been able to find the conclusion of annesse's lesson (just did a quicky search) but I am guessing she might wind this thing up with gut bacteria and fermented foods.

Sorry annesse. I'm really impatient when it comes to satisfying my curiosity. I suppose others might be too. When do we get the secret of the "cure?" Sometimes it is better to work your argument backwards rather than forwards.

Hi Anonymoose~ No problem whatsoever. It is tough to know in what order to put this information up. But unless I present the science first and explain the disease process I don't think the diet and lifestyle approach I recommend would be taken seriously. In addition, unless someone has the "whole" picture they may very well make dietary and lifestyle choices that could derail the entire healing process. Personally, I needed a lot of "evidence" before I was willing to make serious changes. I also think it is important to focus on one thing at a time.

I did just post a link in my profile to our website. It has lots of info on the types of foods etc. that will help heal the GI tract and replace these enzymes. After I get all of the science up, if enough people are interested, we could also think about starting a thread here under the "diet" catagory.

Found it! For those of you who are also horribly impatient, Annesse's recommendations for increasing protease and other enzymes. http://www.naturehaditfirst.com/annesse ... ymes-take/

If you google dietary protease increase, you will also find reference to sprouted grains and nuts and whole grains in general.

One less thing nagging at my mind. This line of thinking seems to run along the lines of fmt...might be something to it.

Again, sorry Annesse. I'm not sure you fully grasp the suffering some of us experience when left with unanswered questions. Also, you would be surprised at what Pwms will try with only the tiniest bit of hope. I predict a run on sauerkraut.