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OK.... i just read the importance of Nitric Oxide for Endothelial Cell health

http://www.ccsvi.org/index.php/helping- ... ial-health

During their research, Furchgott and Ignarro independently discovered that the healthy endothelium secretes substances which protect vascular health. Chief among these is nitric-oxide, a tiny two-atom gas, which is now considered the hallmark of normal endothelial function and the elusive “signaling factor” they had been searching for.

Then i come across this article in PDF format on Dimethylfumarate, or the new oral medication called BG-12
which my wife's neuro wants to put her on next year when it's available.

Microglia are distributed throughout the CNS as a network of resting immunocompetent cells derived from the monocyte/ macrophage lineage. The cells become rapidly activated in response to injury or in the presence of pathogens and - like other tissue macrophages in the first line of host defense - play a pivotal role as phagocytic, antigen-presenting cells. However, it is also this efficient defensive action that makes them potentially neurotoxic cells. By releasing various kinds of noxious factors such as proinflammatory cytokines (i.e. TNF-?, IL-1?, IL-6) or proinflammatory molecules like nitric oxide (NO) microglia may potentiate damage to CNS cells [10-12]. IL-1? [13] and NO [14] are expressed in chronic active plaques in MS patients. NO reacts with superoxide anion to generate peroxynitrite, a highly reactive molecule capable of oxidizing proteins, lipids and DNA; and which mediates microglial toxicity to oligodendrocytes [14] NO can trigger immune cascades that further enhance inflammatory- mediated CNS damage: Increased concentrations of NO can lead to enhanced expression of chemokine (C-CmotifCmotif) ligand 2 (CCL2) on astrocytes which, in turn, leads to infiltration of CD11b cells and additional tissue damage [15].

http://www.biomedcentral.com/content/pd ... 4-7-30.pdf

I don't get it..!!! Nitric Oxide can trigger immune cascades that further enhance inflammatory mediated CNS damage..????

And this article talks about how most neuro's will prescribe BG-12 to their patients..

http://www.medinewsdigest.com/?p=3228

So... am i missing something..????

Bob

Hi Bob--
Nitric oxide is not bad---it's the location that makes the difference
Nitric oxide (NO) is the signaling molecule for the endothelium,
it allows for blood to flow through open vessels, without sticking, thickening or clotting. It is a necessary 2 atom gas in the human body.
It should remain inside the blood brain barrier.
When it escapes through a permeable blood brain barrier, and travels outside the blood vessels into brain tissue, it can do damage via the mechanism of pro-inflammatory cytokines you cited.


An intact cerebral endothelium is not permeable, and it keeps plasmic particles, antigens, metals and other toxins out of reach of brain tissue. We want a healthy blood brain barrier.
(As another example--Iron in plasma is not "bad"...but iron escaping through the blood brain barrier and depositing into brain tissue is bad...it's the same thing with NO.)
I hope the explains the difference.

That's why I wrote up the endothelial health program you linked above and got researchers like Dr. John Cooke looking at CCSVI.
Here's Dr. Cooke discussing the importance of the endothelial layer of the cerebral blood brain barrier----he comes in at 2 minutes.


Here's Dr. Alexander discussing the cerebral endothelium:


make sense?

Now...onto BG-12--which is a synthetic version of natural Nrf2 transcription factor activators, like the natural anti-oxidants EGCG, milk thistle and curcumin--which are in the endothelial health program.

cheer

OK, thanks cheer for putting that into layman's terms..!!! Right now i'm just trying to get as much info
on BG-12 as i can.


Thanks again,

Bob

Bob-
let me help you out, and help your wife out.

Here's a study done by neurologists and presented at ECTRIMS that compared the effectiveness of BG-12 (which, as I told you, is a synthetic replication of natural antioxidants found in food) to a nutritional supplement, called "protandim".
This study was paid for by Biogen, and it found that protandim was actually MORE EFFECTIVE than BG-12, their own product.

Conclusions: Our findings indicate that several Nrf2 activators are able to significantly increase antioxidant enzyme production in oligodendrocytes. Interestingly, protandim, a dietary supplement consisting of herbal ingredients, was the most potent inducer and therefore may be the most suited as a therapeutic strategy. Importantly, Nrf2-mediated antioxidant enzyme expression in oligodendrocytes resulted in enhanced oligodendrocyte survival during an oxidative attack.

http://registration.akm.ch/einsicht.php ... KEN_ID=900


Again....this is a study paid for by pharma, by the actual company that makes BG-12, saying that a nutritional supplement may actually be BETTER than their product at protecting oligodendrocytes during oxidative attack.

Now, protandim is a fine product, but it is marketed by a pyramid marketing company. It's not nearly as expensive as BG-12, but still, it's overpriced... I looked up the ingredients, and the three main ones are EGCG (green tea extract), curcumin (or tumeric, the orange spice in Indian curry) and silymarin (or milk thistle)

My husband has been on these three supplements for four years now as part of the endothelial health program, and his inflammation numbers are down, and he's doing really well. MS is stable and in remission. I don't make anything off this advice. But I think pwMS and their caretakers deserve to know the truth.

cheer

I had run out of two of those three (the milk thistle and the curcumin) and not replaced them for a few months. I think I may move faster on that!

Thanks for the information, as always.

My husband has been on these three supplements for four years now as part of the endothelial health program, and his inflammation numbers are down, and he's doing really well. MS is stable and in remission. I don't make anything off this advice. But I think pwMS and their caretakers deserve to know the truth.

Cheer, i'm glad to here you husband is doing really..!!! "Wow" i can't enough for the additional info..!!! Ever since i've been
visiting tims i'm truly grateful for the for the advice that you provide including the advice and research that Cece, and
jimmylegs provide.

again, i cant thank you enough!!!


Bob

cheerleader wrote:BG-12 (which, as I told you, is a synthetic replication of natural antioxidants found in food)

BG-12, or dimethyl fumarate, is not an antioxidant. It's actually an oxidizing agent that attacks thiol groups like those on cysteine residues or glutathione. It acheives its antioxidant activity by activating the Nrf2 transcription factor via oxidation of the thiol groups on Nrf2's regulatory protein, Keap1. By doing so, it tells the cell that it needs to protect itself from the oxidative stress and Nrf2 then enters the nucleus and activates the transcription of several different antioxidant enzymes. It is from these enzymes that stems the antioxidant protection. Think of BG-12 as the fire that get's things going and the antioxidant enzymes as the water to put out that fire. Moreover, since they're enzymes with catalytic activity and not used up like a simple antioxidant, there's also enough water for the drought-stricken crops as well.

Now, protandim is a fine product, but it is marketed by a pyramid marketing company. It's not nearly as expensive as BG-12, but still, it's overpriced... I looked up the ingredients, and the three main ones are EGCG (green tea extract), curcumin (or tumeric, the orange spice in Indian curry) and silymarin (or milk thistle).

Some thoughts on protandim's ingrediets regarding curcumin and EGCG: 75 mg curcumin - about equal to just under (~ 80%) 1 teaspoon of whole turmeric, 75 mg of EGCG - about equal to 1-1.5 cups of green tea. It's just not very impressive. Many studies using curcumin use around 6 g per day due to its low bioavailability and most references on green tea state that you need to drink around 4 or more cups per day which would yield 200-400 mg of catechins. Note that I have yet to research protandim's other ingredients, but just found an interesting article on Medscape that discusses silymarin.

http://www.medscape.com/viewarticle/422884

My husband has been on these three supplements for four years now as part of the endothelial health program, and his inflammation numbers are down, and he's doing really well. MS is stable and in remission. I don't make anything off this advice. But I think pwMS and their caretakers deserve to know the truth.

By the way, I was wondering if Jeff is still taking nattokinase?

NHE

Sorry, NHE-trying to keep the BG-12/Nrf2 activator explanation simple for Bob.
You are absolutely right--It is an oxidizing agent that makes the body respond with antioxidizing enzymes. Your fire analogy is perfect. The larger point I was making is that it is a synthetic derivative which mimics other Nrf2 activators--esepcially the ones that have been studied extensively: curcumin, silymarin and EGCG. I don't want that point to get lost. That BG-12 study paid for by Biogen and presented at ECTRIMS is a big deal.

Protandim is made up of phytochemicals---phyto, meaning plant.
http://lpi.oregonstate.edu/infocenter/p ... icals.html

Here is the study where I found the ingredients listed:

The biological actions of curcumin, silymarin, and EGCG have been extensively studied. Very limited information is available regarding the other two ingredients,namely,ashwaganda and bacopa. Both are used in Ayurvedic medicine and studies have demonstrated their beneficial effects. Alcoholic extracts of ashwagandha administered to rats exert neuroprotective effects against 6-hydroxydopamine-induced oxidative stress[46]. The markers of oxidative stress were improved by ashwagandha. Several studies have demonstrated the antioxidant effects of extract of B. monniera invivo[47-49]. The active glycosides from this herb have been isolated and characterized[50]

No more nattokinase for Jeff. His coagulation numbers are great. His regimen now for the past year is 1000mg. curcumin, 1000mg.EGCG, 500mg. each bromelain/quercetin, 3 grams Omega 3, 4000IU vitamin D, 200 mg milk thistle, mag/calcium/zinc combo, and 150 mg.papaya enzyme. Swank Diet, no sugar, white foods, red meat. He doesn't smoke or drink, eats whole foods, not processed. Exercises everday. Meditates, regulates work stress. Laughs a lot more

HTH,
cheer

cheerleader wrote:Sorry, NHE-trying to keep the BG-12/Nrf2 activator explanation simple for Bob.
You are absolutely right--It is an oxidizing agent that makes the body respond with antioxidizing enzymes. Your fire analogy is perfect. The larger point I was making is that it is a synthetic derivative which mimics other Nrf2 activators--esepcially the ones that have been studied extensively: curcumin, silymarin and EGCG. I don't want that point to get lost. That BG-12 study paid for by Biogen and presented at ECTRIMS is a big deal.

Protandim is made up of phytochemicals---phyto, meaning plant.
http://lpi.oregonstate.edu/infocenter/p ... icals.html

Here is the study where I found the ingredients listed:

The biological actions of curcumin, silymarin, and EGCG have been extensively studied. Very limited information is available regarding the other two ingredients,namely,ashwaganda and bacopa. Both are used in Ayurvedic medicine and studies have demonstrated their beneficial effects. Alcoholic extracts of ashwagandha administered to rats exert neuroprotective effects against 6-hydroxydopamine-induced oxidative stress[46]. The markers of oxidative stress were improved by ashwagandha. Several studies have demonstrated the antioxidant effects of extract of B. monniera invivo[47-49]. The active glycosides from this herb have been isolated and characterized[50]

No more nattokinase for Jeff. His coagulation numbers are great. His regimen now for the past year is 1000mg. curcumin, 1000mg.EGCG, 500mg. each bromelain/quercetin, 3 grams Omega 3, 4000IU vitamin D, 200 mg milk thistle, mag/calcium/zinc combo, and 150 mg.papaya enzyme. Swank Diet, no sugar, white foods, red meat. He doesn't smoke or drink, eats whole foods, not processed. Exercises everday. Meditates, regulates work stress. Laughs a lot more

HTH,
cheer

Hi cheer, i'm assuming Jeff is NOT on any DMD..????


Bob

cheerleader wrote:No more nattokinase for Jeff. His coagulation numbers are great. His regimen now for the past year is 1000mg. curcumin, 1000mg.EGCG, 500mg. each bromelain/quercetin, 3 grams Omega 3, 4000IU vitamin D, 200 mg milk thistle, mag/calcium/zinc combo, and 150 mg.papaya enzyme. Swank Diet, no sugar, white foods, red meat. He doesn't smoke or drink, eats whole foods, not processed. Exercises everday. Meditates, regulates work stress. Laughs a lot more

How long did Jeff take nattokinase after receiving stents from Dr. Dake? What role do you think nattokinase may have played in his treatment success? I often wonder if nattokinase should be used more regularly post CCSVI treatment. What are your thoughts on this?


Effect of nattokinase on restenosis after percutaneous transluminal angioplasty of the abdominal artery in rabbits.
Nan Fang Yi Ke Da Xue Xue Bao. 2008 Aug;28(9):1538-41.

• OBJECTIVE: To investigate the effect of nattokinase on intimal hyperplasia in rabbit abdominal artery after balloon injury and explore a novel strategy for the preventing restenosis after percutaneous transluminal angioplasty.
  
  METHODS: Fifty-six New Zealand rabbits were randomly divided into 7 groups, namely the solvent control group, model group, natto extract lavage group, refined nattokinse lavage group, intravenous refined nattokinse injection group, clopidogrel group and clopidogrel-aspirin group. Balloon injury was induced by inserting the catheter through the femoral artery into the thoracic aorta of the rabbits. The platelet counts were notad and platelet aggregation was observed, and the abdominal artery was taken for pathological analysis. The expressions of MMP-2 and -9 in the abdominal artery were detected immunohistochemically.
  
  RESULTS: There was no significant difference in the platelet counts, platelet aggregation rate or MMP-2 and -9 expression between the model group and the nattokinse-treated groups (P>0.05). The stenosis index in each nattokinse-treated group was significantly greater and the neointimal proliferation index smaller than that of the model group (P<0.01 or 0.05).
  
  CONCLUSION: Nattokinse can inhibit restenosis of rabbit abdominal artery after percutaneous transluminal angioplasty, which is independent of its actions on the platelet or MMP-2 and -9 expressions.

NHE

Cheer is away at the SIR conference (wish I was too!) but she has said many times that Jeff remains on Copaxone:
http://www.thisisms.com/forum/chronic-c ... ml#p113633