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Annesse wrote:

It is the inability to properly "metabolize" vitamin B12 due to a lack of enzymes, specifically protease and DNase 1, that I believe the evidence shows is the reason for the low vitamin B12 and resulting high homocysteine found in Alzheimer's disease and MS.

In the following study the researchers stated that there is increasing evidence for an association between Alzheimer’s disease and “nutritionally independent” cobalamin (vitamin B12) deficiency. The researchers believe this may be due to a PROTEASE inhibition, a "common factor" in Alzheimer’s disease. The lack of protease results in protein-bound cobalamin malabsorption and disrupted cobalamin metabolism.

Trypsin inhibition: a potential cause of cobalamin deficiency common to the pathogenesis of Alzheimer-type dementia and AIDS dementia complex?
McCaddon, A., B. Regland, C.F. Fear. 1995. Med Hypotheses. 45(2):200-4.

“There is increasing evidence for an association between Alzheimer-type dementia (AD) and nutritionally independent cobalamin deficiency. Furthermore, low serum cobalamin values occur in a kindred with familial Alzheimer's disease (FAD) and histopathological confirmation of AD neuropathology…This paper presents the hypothesis that protease inhibition is a common factor in AD and ADC resulting in protein-bound cobalamin malabsorption and disrupted cobalamin metabolism.”

In addition to low vitamin B12 and elevated homocysteine, there are many more disease ramifications that would result from these missing enzymes. A lack of these enzymes results in other nutrients that are not being properly metabolized as well. The question is, should you take these nutrients in supplement form if your body is unable to properly metabolize them? Is there a possibility you may see an increased risk of disease? I will be providing some more information on this.

Hi Annesse,

I've been dependant on B12 for over 20 years now (injections) but more so since MS diagnosis and since SPMS 3 years ago I've had little or no benefit from B12 shots even though I began taking them with increased frequency. Have assumed it was malabsorption of some kind but can't resolve. I used to respond so well - numbness in hands, mobility, quality of sleep etc. - all lost now. Wondering where to go now.

PN

Hi PN~

I would focus on the "cause" of the inability to properly metabolize vitamin B12, which is, in my opinion, the lack of protease and DNase 1. As important as vitamin B12 is, there is much more going on in the disease process , so you need to first learn as much as you can about the disease process itself and then tailor your decisions accordingly. You can restore these enzymes through diet though with no risks of side effects. We can discuss more about this once you have more information on the disease process.


The absorption of vitamin B12 is an amazingly complex process. A recent study from Norway may be an indication that it might be best if we don’t interfere with this process by taking vitamin B12 supplements.

In the study, published in the Journal of the American Medical Association, the researchers found that supplementation with vitamin B12 and folic acid increased the risk of being diagnosed with cancer, of dying from cancer, and of dying from any cause.

Here are the numbers:

“The study was a double-blind, placebo-controlled, randomized clinical trial in which nearly 7,000 adults in Norway were randomly selected to take one of the following:

• 0.8 mg of folic acid + 0.4 mg of vitamin B12 + 40 mg vitamin B6 per day
• 0.8 mg of folic acid + 0.4 mg of vitamin B12 per day
• 40 mg vitamin B6 per day
• placebo (no vitamins)

Double-blind means that neither the researchers nor the study participants knew who was taking which vitamins or the placebo. Randomized means that people were selected at random for each vitamin (or placebo) group. This type of study is considered “the gold standard” of research designs, because it is most likely to show results accurately, without errors that can happen with other study designs.
Study participants were followed for a median (similar to average) of approximately six and a half years (39 months of active study participation plus 38 months of post-study observation). The study showed that compared with people not receiving folic acid and vitamin B12, those who took these vitamins had:

• 21% higher risk of being diagnosed with cancer (any type)
• 38% higher risk of dying of cancer (any type)
• 18% higher risk of dying of any cause

Taking vitamin B6 did not have any measurable effects (good or bad) on the health of the study participants” (Dixon, 2009).


Vitamin B12 is an essential vitamin for the division of all cells, but rapidly dividing cancer cells, in particular, require vitamin B12 to sustain their rapid growth. Consequently, the receptors involved in the uptake of vitamin B12 are overexpressed on the cancer cell surface (Russell-Jones, 2004). Armed with this knowledge, pharmaceutical companies are actually designing new drugs that use supplemental vitamin B12 as the transport mechanism to deliver cytotoxic agents to cancerous tumors.

The overexpression of vitamin B12 receptors on cancer cells would explain the large increased risk of cancer from supplemental vitamin B12 found in the study from Norway. In addition, the inability to properly absorb vitamin B12 would add to the risk that cancer cells, rather than normal healthy cells, would benefit from supplemental vitamin B12.

Here is a study on vitamin B12 being used as a potential tool for the delivery of cytotoxic agents to cancer cells.

http://www.ncbi.nlm.nih.gov/pubmed/18540842

Annesse,

Can I supplement with protease and DNase to achieve proper absorption?

PN

Hi PN~

DNase 1 doesn't exist in supplement form.

Here is some info from my fibromyalgia book on protease supplementation.

"Protease Supplements

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."

In the previous study I posted on homocysteine and glutamate toxicity the researchers concluded that homocysteine compromises neuronal homeostasis by multiple, divergent routes. In addition to stimulating glutamate excitotoxicity, homocysteine also damages DNA. DNA damage activates a protein called poly ADP-ribose polymerase (PARP) that can trigger inflammation and cell death and is involved in oligodendrocyte loss and demyelination. Here is the study again.

J Neurosci Res. 2002 Dec 1;70(5):694-702.
Multiple aspects of homocysteine neurotoxicity: glutamate excitotoxicity, kinase hyperactivation and DNA damage.
Ho PI, Ortiz D, Rogers E, Shea TB.

“Homocysteine (HC) is a neurotoxic amino acid that accumulates in several neurological disorders including Alzheimer's disease (AD)…Homocysteine-induced calcium influx through NMDA channel activation, which stimulated glutamate excitotoxicity…Apoptosis after HC treatment was reduced by co-treatment with 3-aminobenazmidine (3ab), an inhibitor of poly-ADP-ribosome polymerase (PARP), consistent with previous reports that ATP depletion by PARP-mediated repair of DNA strand breakage mediated HC-induced apoptosis.These findings indicate that HC compromises neuronal homeostasis by multiple, divergent routes.”




In the following study the researchers concluded their data demonstrated "PARP" activation within apoptotic oligodendrocytes and state in the title that inhibiting PARP may be a "potential therapy" against oligodendrocyte death.


Brain. 2010 Mar;133(Pt 3):822-34. doi: 10.1093/brain/awp337. Epub 2010 Feb 15.
Inhibiting poly(ADP-ribose) polymerase: a potential therapy against oligodendrocyte death.
Veto S, Acs P, Bauer J, Lassmann H, Berente Z, Setalo G Jr, Borgulya G, Sumegi B, Komoly S, Gallyas F Jr, Illes Z.

“Oligodendrocyte loss and demyelination are major pathological hallmarks of multiple sclerosis. In pattern III lesions, inflammation is minor in the early stages, and oligodendrocyte apoptosis prevails, which appears to be mediated at least in part through mitochondrial injury. Here, we demonstrate poly(ADP-ribose) polymerase activation and apoptosis inducing factor nuclear translocation within apoptotic oligodendrocytes in such multiple sclerosis lesions. The same morphological and molecular pathology was observed in an experimental model of primary demyelination, induced by the mitochondrial toxin cuprizone. Inhibition of poly(ADP-ribose) polymerase in this model attenuated oligodendrocyte depletion and decreased demyelination…Our data indicate that poly(ADP-ribose) polymerase activation plays a crucial role in the pathogenesis of pattern III multiple sclerosis lesions. Since poly(ADP-ribose) polymerase inhibition was also effective in the inflammatory model of multiple sclerosis, it may target all subtypes of multiple sclerosis, either by preventing oligodendrocyte death or attenuating inflammation.”



In the following study the researchers also discuss targeting PARP as a promising approach for treatment of MS.


Trends Mol Med. 2012 Feb;18(2):92-100. doi: 10.1016/j.molmed.2011.10.002. Epub 2011 Nov 9.
Targeting poly(ADP-ribose) polymerase-1 as a promising approach for immunomodulation in multiple sclerosis?
Cavone L, Chiarugi A.

“Despite significant advancement in developing therapies for multiple sclerosis (MS), drugs that cure this devastating disorder are an unmet need. Among the remedies showing efficacy in preclinical MS models, inhibitors of poly(ADP-ribose) polymerase (PARP)-1 have gained great momentum. Emerging evidence demonstrates that PARP-1 inhibitors epigenetically regulate gene expression and finely tune transcriptional activation in immune and neural cells. In this review, we present an appraisal of the effects of PARP-1 and its inhibitors on immune activation, with particular emphasis on the processes taking place during the autoimmune attack directed against the central nervous system. One explanation is that drugs inhibiting PARP-1 activity protect from neuroinflammation in MS models via immunomodulation and direct neuroprotection. PARP-1 inhibitors have already reached the clinical arena as cancer treatments, and observations made in treating these patients could help advance treatments for MS.”


The antibiotic "minocycline", one of the medications used in the treatment of MS inhibits PARP.


Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9685-90. Epub 2006 Jun 12.

Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrations.
Alano CC, Kauppinen TM, Valls AV, Swanson RA.

“Poly(ADP-ribose) polymerase-1 (PARP-1), when activated by DNA damage, promotes both cell death and inflammation. Here we report that PARP-1 enzymatic activity is directly inhibited by minocycline and other tetracycline derivatives that have previously been shown to have neuroprotective and anti-inflammatory actions…”


In the following study the researchers concluded that activation of PARP "occurs rapidly" after exposure to homocysteine.

Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity.
http://www.jneurosci.org/content/20/18/6920.short

“Elevated plasma levels of the sulfur-containing amino acid homocysteine increase the risk for atherosclerosis, stroke, and possibly Alzheimer's disease, but the underlying mechanisms are unknown. We now report that homocysteine induces apoptosis in rat hippocampal neurons. DNA strand breaks and associated activation of poly-ADP-ribose polymerase (PARP) and NAD depletion occur rapidly after exposure to homocysteine and precede mitochondrial dysfunction, oxidative stress, and caspase activation…Homocysteine markedly increases the vulnerability of hippocampal neurons to excitotoxic and oxidative injury in cell culture and in vivo, suggesting a mechanism by which homocysteine may contribute to the pathogenesis of neurodegenerative disorders.”

In the previous study I posted the researchers concluded that along with DNA strand breaks and the rapid activation of PARP, homocysteine exposure rapidly depleted "nicotinamide adenine dinucleotide". Nicotinamide adenine dinucleotide (NAD) is a coenzyme involved in the cellular respiration processes of all living cells. In the following study from Harvard Medical School on axonal degeneration and NAD the researchers concluded, "Furthermore, nicotinamide (NAm), an NAD biosynthesis precursor, profoundly prevents the degeneration of demyelinated axons and improves the behavioral deficits in EAE models..."






J Neurosci. 2006 Sep 20;26(38):9794-804.

Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models.

Kaneko S, Wang J, Kaneko M, Yiu G, Hurrell JM, Chitnis T, Khoury SJ, He Z.
SourceDivision of Neuroscience, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract
Axonal damage is a major morphological alteration in the CNS of patients with multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the underlying mechanism for the axonal damage associated with MS/EAE and its contribution to the clinical symptoms remain unclear. The expression of a fusion protein, named "Wallerian degeneration slow" (Wld(S)), can protect axons from degeneration, likely through a beta-nicotinamide adenine dinucleotide (NAD)-dependent mechanism. In this study, we find that, when induced with EAE, Wld(S) mice showed a modest attenuation of behavioral deficits and axon loss, suggesting that EAE-associated axon damage may occur by a mechanism similar to Wallerian degeneration. Furthermore, nicotinamide (NAm), an NAD biosynthesis precursor, profoundly prevents the degeneration of demyelinated axons and improves the behavioral deficits in EAE models..."

Homocysteine also increases the expression of the pro-iflammatory chemokine-monocyte chemoattractant protein-1 (MCP-1). MCP-1 is a key chemokine that regulates migration and infiltration of monocytes/macrophages. In the following study the researchers stated, “In particular, monocyte chemoattractant protein 1 (MCP-1) has been implicated in diseases characterized by monocyte-rich infiltrates, including atherosclerosis, rheumatoid arthritis and multiple sclerosis.”

Mol Med Today. 1996 May;2(5):198-204.
Monocyte chemoattractant protein 1: a potential regulator of monocyte recruitment in inflammatory disease.
Rollins BJ.

“The appearance of specific types of leukocytes in inflammatory infiltrates may be governed by cell-specific chemoattractants called chemokines. In particular, monocyte chemoattractant protein 1 (MCP-1) has been implicated in diseases characterized by monocyte-rich infiltrates, including atherosclerosis, rheumatoid arthritis and multiple sclerosis…”




In the following study published in Molecular and Cellular Biochemistry the researchers found that the secretion of MCP-1 protein was increased "195%" in cells treated with homocysteine.

Mol Cell Biochem. 2001 Jan;216(1-2):121-8.
Homocysteine stimulates the expression of monocyte chemoattractant protein-1 in endothelial cells leading to enhanced monocyte chemotaxis.
Sung FL, Slow YL, Wang G, Lynn EG, O K.

Hyperhomocysteinemia has been identified as an independent risk factor for atherosclerosis. The infiltration of monocytes into the arterial wall is one of the key events during atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that stimulates the migration of monocytes into the intima of the arterial wall. The mechanism by which increased monocyte infiltration occurs in atherosclerotic lesions in patients with hyperhomocysteinemia has not been delineated. The objective of the present study was to investigate the effect of homocysteine on MCP-1 production in endothelial cells. Cells were incubated with homocysteine. The secretion of MCP-1 protein was significantly increased (195% as compared to the control) in cells treated with pathological concentrations of homocysteine. Such effect was accompanied by an increased expression of MCP-1 mRNA (176% as compared to the control) in endothelial cells which resulted in enhanced monocyte chemotaxis. The p38 MAP kinase as well as other members of the p38 MAP kinase pathway, including MKK3, MKK6, ATF-2 and Elk-1, were activated in homocysteine-treated cells. Homocysteine-induced MCP-1 expression and subsequent monocyte chemotaxis were blocked by a p38 MAP kinase inhibitor (SB203580) suggesting that the p38 MAP kinase pathway might be involved in homocysteine-induced MCP-1 expression in endothelial cells. In contrast, staurosporine, a protein kinase C inhibitor, had no effect on homocysteine-induced MCP-1 expression. In conclusion, our results indicate that homocysteine stimulates MCP-1 expression in endothelial cells leading to enhanced monocyte chemotaxis.

In the previous study the researchers stated that the p38 MAP kinase (MAPK) pathway was activated in homocysteine-treated cells. The p38 MAPK pathway is a signaling pathway known to contribute to inflammatory responses. In the following study the researchers stated that a number of recent studies have identified the p38 MAPK pathway as a "central player" in MS.

Mol Cell Biol. 2013 Jul 29.
The emerging role of p38 MAP kinase in multiple sclerosis and its models.
Krementsov DN, Thornton TM, Teuscher C, Rincon M.

“Multiple sclerosis (MS), the most common disabling neurologic disease of young adults, is considered a classical T cell-mediated disease and is characterized by demyelination, axonal damage, and progressive neurological dysfunction. Currently available disease modifying therapies are limited in their efficacy, and improved understanding of new pathways contributing to disease pathogenesis could reveal additional novel therapeutic targets. The p38 MAP kinase (MAPK) signaling pathway is known to be triggered by stress stimuli and to contribute to inflammatory responses. Importantly, a number of recent studies have identified this signaling pathway as a central player in MS and its principal animal model, experimental allergic encephalomyelitis. Here, we review the evidence from mouse and human studies supporting the role of p38 MAPK in regulating key immunopathogenic mechanisms underlying autoimmune inflammatory disease of the central nervous system, and the potential of targeting this pathway as a disease modifying therapy in MS.”

Researchers in our next study stated that “p38 MAPK activation is required for the development and progression of both chronic and relapsing-remitting forms of experimental allergic encephalomyelitis (EAE), the principal autoimmune model of multiple sclerosis.” In addition, the researchers concluded that the p38 MAPK signaling pathway is essential for in vitro and in vivo IL-17 production by regulating IL-17 synthesis in CD4 T cells.

Blood. 2011 Sep 22;118(12):3290-300. doi: 10.1182/blood-2011-02-336552. Epub 2011 Jul 25.
Activation of p38 MAPK in CD4 T cells controls IL-17 production and autoimmune encephalomyelitis.
Noubade R, Krementsov DN, Del Rio R, Thornton T, Nagaleekar V, Saligrama N, Spitzack A, Spach K, Sabio G, Davis RJ, Rincon M, Teuscher C.

“Although several transcription factors have been shown to be critical for the induction and maintenance of IL-17 expression by CD4 Th cells, less is known about the role of nontranscriptional mechanisms. Here we show that the p38 MAPK signaling pathway is essential for in vitro and in vivo IL-17 production by regulating IL-17 synthesis in CD4 T cells through the activation of the eukaryotic translation initiation factor 4E/MAPK-interacting kinase (eIF-4E/MNK) pathway. We also show that p38 MAPK activation is required for the development and progression of both chronic and relapsing-remitting forms of experimental allergic encephalomyelitis (EAE), the principal autoimmune model of multiple sclerosis. Furthermore, we show that regulation of p38 MAPK activity specifically in T cells is sufficient to modulate EAE severity. Thus, mechanisms other than the regulation of gene expression also contribute to Th17 cell effector functions and, potentially, to the pathogenesis of other Th17 cell-mediated diseases.”

I thought this was interesting. Homocysteine has also been shown to interfere with the formation of collagen. In the following study published in The Journal of Clinical Investigation the researchers stated, “It is concluded that homocysteine interferes with the formation of intermolecular cross-links that help stabilize the collagen macromolecular network.”

A collagen defect in homocystinuria.
Kang, A.H., R.L. Trelstad. 1973. J Clin Invest 52(10):2571-8.

“It is concluded that homocysteine interferes with the formation of intermolecular cross-links that help stabilize the collagen macromolecular network.”



The interference by homocysteine in the formation of collagen would explain the association MS has with Ehlers-Danlos syndrome. Ehlers-Danlos syndrome (EDS) is a group of connective tissue disorders caused by a defect in the synthesis of collagen (Type I or III). In the following study published in Multiple Sclerosis the researchers found a 10-11 time increased prevalence of EDS in MS patients. The researchers concluded that this association may be due to a possible causal relationship on a connective tissue level.

Ehlers-Danlos syndrome and multiple sclerosis: a possible association.
Mult Scler. 2008; 14(4):567-70 (ISSN: 1352-4585)
Vilisaar J; Harikrishnan S; Suri M; Constantinescu CS

“… Here we present an association of EDS with multiple sclerosis (MS)…This frequency suggests 10-11 times increased prevalence of EDS in MS patients compared with the general population… Suggested implications include a possible causal relationship on a connective tissue level with a higher susceptibility to MS in EDS…”

The problem with your claim, annesse, is that whole genome analysis of multiple sclerosis patients has been done extensively at USCF, and deficiency/polymorphism of genes related to protease and DNase 1 was not found.

Also, B12 is highly variable among MS patients (for example standard deviation was ~210 in this study: http://www.ncbi.nlm.nih.gov/pubmed/23756083)

This is not to say that nutrition/metabolism is unrelated to MS, but it is certainly much more complex than you describe. I don't think your statement "I believe that MS originates with a lack of enzymes called protease and DNase 1" is reasonable at all.

Hi centenarian100~

In the following study from Mayo College of Medicine the researchers stated that an “array of studies” implicate protease in multiple sclerosis pathogenesis.


Curr Top Microbiol Immunol. 2008;318:133-75.
The multiple sclerosis degradome: enzymatic cascades in development and progression of central nervous system inflammatory disease.
Scarisbrick IA.
“An array of studies implicate different classes of protease and their endogenous inhibitors in multiple sclerosis (MS) pathogenesis based on expression patterns in MS lesions, sera, and/or cerebrospinal fluid (CSF). Growing evidence exists regarding their mechanistic roles in inflammatory and neurodegenerative aspects of this disease…”

As far as the B12 is concerned, I have a great deal more evidence to present concerning its involvement in MS. In addition, the problem with B12 lies in the binding and transport into the cells, so blood levels would not be a reliable indicator.

In the following study researchers from Japan found that MS patients have a decrease in the binding capacity of vitamin B12, thus inhibiting the transport of vitamin B12 into the cells, even with normal levels in their blood.




Intern Med. 1994 Feb;33(2):82-6.
Vitamin B12 metabolism and massive-dose methyl vitamin B12 therapy in Japanese patients with multiple sclerosis.
Kira J, Tobimatsu S, Goto I.

“Serum vitamin B12 levels and unsaturated vitamin B12 binding capacities were measured in 24 patients with multiple sclerosis (MS), 73 patients with other neurological disorders and 21 healthy subjects. There was no decrease in the vitamin B12 levels, however, a significant decrease in the unsaturated vitamin B12 binding capacities was observed in patients with MS when compared with other groups…”


I too believe that the disease process of MS is extremely involved and complicated, but that does not mean that these missing enzymes could not very well lead to a complicated disease process, similar to, if not identical to MS. For instance, a lack of DNase 1 has been determined to be a "causative" factor of lupus. Here are a few studies on this.

Lupus and deoxyribonuclease.
Lachmann, P.J., 2003. Lupus 12(3):202-6.
“Mice whose DNase 1 gene is knocked out are known to develop lupus and to be otherwise normal.”


Mutation of DNASE1 in people with systemic lupus erythematosus.
Yasutomo, K., T. Horiuchi, S. Kagami, H. Tsukamoto, C. Hashimura, M. Urushihara, Y. Kuroda. 2001. Nat. Genet. 28(4):313-4.
“These data are consistent with the hypothesis that a direct connection exists between low activity of DNASE1 and progression of human SLE.”

Do lupus patients lack vitamin B12 and have high homocysteine due to these missing enzymes?

In the following study the researchers discovered that vitamin B12 levels were significantly lower in lupus (SLE) patients.

Serum cobalamin and transcobalamin levels in systemic lupus erythematosus.
Molad, Y., B. Rachmilewitz, Y. Sidi, J. Pinkhas, A. Weinberger. 1990. Am J Med. 88(2):141-4.
“…Cobalamin levels were found to be significantly lower in the SLE group compared with a normal control group…”

Low B12 will lead to high homocysteine and the same increased risk of cardiovascular disease as found in MS.
Researchers at Johns Hopkins Medical Institutions found that lupus (SLE) patients have an increased risk
of suffering strokes, heart attacks, and other arterial thrombotic events, such as gangrene of the fingers (Petri, 1996). They attributed this higher risk to a greater propensity among SLE patients to develop
premature atherosclerosis (hardening of the arteries) due to a lack of vitamin B12, and the subsequent rise in homocysteine. The researchers concluded, “SLE patients with elevated homocysteine levels have a 2.4 times higher risk of having a stroke and a 3.5 times higher risk of having an arterial thrombotic event.”


The elevated homocysteine found in lupus would also lead to endothelial dysfunction, just as in MS.

The following information from the University of Michigan highlights the increased risk of heart disease for lupus patients. The researchers concluded that something must be damaging the endothelial cell layer to cause the protective cells to commit “mass suicide”.

U-M study: high heart disease risk for lupus patients may be linked to rapid
death of blood vessel lining cells.

Gavin, K., 11 November 2003.

Mass suicide by protective cells that line every blood vessel in the body may be to
blame for the increased risk of heart and vascular disease faced by patients with
the autoimmune disease known as lupus, new research suggests.

The new study suggests that lupus patients’ heightened heart risk may be due
to the rapid death and much-too-slow replacement of endothelial cells, which
normally keep plaques and clots from forming in blood vessels. Loss of these cells
through accelerated apoptosis may affect vascular and heart health in many ways,
says Rajagopalan, since endothelial cells serve an important barrier function, and
make nitric oxide that regulates blood vessel dilation and contraction and blood
flow.

Rajagopalan and Kaplan, along with a team of U-M colleagues, suspected
something must be damaging the endothelial cell layer in order to cause
cardiovascular disease in women with no other risk factors besides lupus. They
set out to determine if they could see these apoptotic endothelial cells in the
blood, and correlate them to both vascular function and the flaring up of lupus
symptoms.

“We hypothesized that rapid apoptosis could exist at the level of the endothelial
cells, that they might commit suicide and thereby affect vascular function,” says
Rajagopalan.

Annesse wrote:I too believe that the disease process of MS is extremely involved and complicated, but that does not mean that these missing enzymes could not very well lead to a complicated disease process, similar to, if not identical to MS. For instance, a lack of DNase 1 has been determined to be a "causative" factor of lupus. Here are a few studies on this.

There is a big difference between saying that something is a "causitive factor" and that something is the "cause" of a disease.

For instance, exercise is well known to be inversely related to the risk of cardiovascular disease, and this correlation is likely causitive, but no one would say that sedentary lifestyle is the "cause" of cardiovascular disease.

Your diction implies that you have discovered a single root cause of MS, and you don't have the evidence to back it up. I find this highly offensive.

Ironically, the protease most known to be associated with multiple sclerosis is matrix metalloproteinase -9 which is INCREASED around multiple sclerosis plaques and in EAE articles

source: http://brain.oxfordjournals.org/content ... 2327.short

(I could list many others)

I highly doubt that you read the articles which you quoted in your above post, as this is mentioned here:

http://www.ncbi.nlm.nih.gov/pubmed/?ter ... ry+disease

(where you go this quote: “An array of studies implicate different classes of protease and their endogenous inhibitors in multiple sclerosis (MS) pathogenesis based on expression patterns in MS lesions, sera, and/or cerebrospinal fluid (CSF). Growing evidence exists regarding their mechanistic roles in inflammatory and neurodegenerative aspects of this disease…” )

Yes I know. I'm a jerk...but I can't stand this style of discussion

Hi centenarian100~

You stated:
"Your diction implies that you have discovered a single root cause of MS, and you don't have the evidence to back it up."

There are other pathways that are involved in the disease process of MS due to these missing enzymes. The homocysteine pathway is just one and I am only a quarter of a way through it. So, I have not even begun to present the evidence that links these enzymes to MS.

I think we can agree to disagree, but without seeing all of the evidence it might be too soon to make a judgement call.

I just wanted to clarify something.

centenarian100 stated:

"Ironically, the protease most known to be associated with multiple sclerosis is matrix metalloproteinase -9 which is INCREASED around multiple sclerosis plaques and in EAE articles."

The "digestive enzymes" that digest dietary proteins are called protease. Protease such as pepsin, trypsin, and chymotrypsin digest the proteins in food. There are different classes of protease, however, such as matrix metalloproteinase-9, that do not perform this function.

Here is a link to some information on matrix metalloproteinase-9.

http://en.wikipedia.org/wiki/Matrix_metalloproteinase


This is what I stated at the beginning of this thread:

"As some of you know, I believe that MS originates with a lack of enzymes called protease and DNase1. These enzymes digest dietary DNA and proteins.

I was not referring to matrix metalloproteinase-9.