Reversing Endothelial Dysfunction

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Re: Reversing Endothelial Dysfunction

Postby cheerleader » Sun May 25, 2014 1:08 pm

Hi Scott--
Actually, I've recently discussed L-Arginine supplementation with Dr. John Cooke (Stanford, author of Cardiovascular Cure) and during the last 7 years, his position and that of his colleagues has changed on L-Arginine supplementation. They no longer recommend it.

However, two well-designed studies raised red flags about arginine supplements and the heart. One, conducted by researchers at Stanford University and published in Circulation in 2007, found that arginine supplements did not help people with peripheral arterial disease and may even have made matters worse. “Not useful” was the conclusion. And a study at Johns Hopkins Hospital in 2006 found that arginine supplements given to heart attack patients dramatically increased deaths. The study had to be halted; researchers warned strongly against using arginine for heart attack patients.

http://www.berkeleywellness.com/supplem ... -can-it-do
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069795/
http://www.nutritionandmetabolism.com/content/9/1/54
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132190/

What Dr. Cooke and cardiovascular researchers are saying is that it takes lifestyle changes, not supplements.
I never put L-Arginine in the Endothelial Health program--because the theory is that rather than using a supplement to increase nitric oxide, it's best to let the body create its own.... (You're right to differentiate iNOS and eNOS)
Increasing endothelially derived NO takes a lifestyle. Complete with UV rays, whole foods, smoking cessation, exercise, meditation, weight loss (if indicated) and a bunch of other measures.
http://www.ccsvi.org/index.php/helping- ... ial-health
It works, but it takes work.
HTH,
cheer
Last edited by cheerleader on Sun May 25, 2014 1:22 pm, edited 1 time in total.
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Re: Reversing Endothelial Dysfunction

Postby cheerleader » Sun May 25, 2014 1:12 pm

Here's the bump post and update from the last page....
since it's been another healthy year for Jeff.

Seven years past diagnosis.
Continued health for Jeff, no MS progression, no new lesions, reversal of gray matter atrophy on MRI. Jogging, skiing, working full days.
We're hearing more about the endothelium and multiple sclerosis
http://www.ncbi.nlm.nih.gov/pubmed/24416810
http://www.ncbi.nlm.nih.gov/pubmed/24228622

Here's the complete program:
http://www.ccsvi.org/index.php/helping- ... ial-health

Here are new, specific posts on how endothelial health is created by:
aerobic exercise
http://ccsviinms.blogspot.com/2013/11/a ... otion.html
"good" cholesterol and whole foods
http://ccsviinms.blogspot.com/2013/11/g ... brain.html
UV Rays
http://ccsviinms.blogspot.com/2014/04/m ... mptom.html
http://ccsviinms.blogspot.com/2013/06/p ... -june.html

hope this can help someone else,
cheer
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Re: Reversing Endothelial Dysfunction

Postby THX1138 » Sun May 25, 2014 4:09 pm

Chapter 9
The role of magnesium in edema and blood brain barrier disruption

from the E-Book: Magnesium in the Central Nervous System http://www.adelaide.edu.au/press/titles/magnesium/magnesium-ebook.pdf
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Re: Reversing Endothelial Dysfunction

Postby cheerleader » Sun May 25, 2014 6:14 pm

Hi THX, great book!---That's exactly why magnesium is # 10 on the Endothelial Health Program---
because this mineral is essential to endothelial integrity, and the deficiency of mg can lead to dysfunction.
Here's the link to the program one more time, for those who haven't seen it.
There are 11 steps--too long to copy and paste over here, but worth checking out.
http://ccsvi.org/index.php/helping-myse ... ial-health

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Re: Reversing Endothelial Dysfunction

Postby Scott1 » Mon May 26, 2014 1:59 am

Hi Cheer,

I'm not sure were on opposite sides of the fence. Your third article says-

"Others studies also have showed improvements in NO production by using L-arginine supplementation [30-33]. However, all of these studies had administered L-arginine in subjects with some cardiovascular risk factors or cardiopathy. It appears that L-arginine is a limiting factor for NO synthesis in patients at risk for atherosclerosis, but not for healthy individuals [34]. Therefore, L-arginine supplementation may be necessary only for individuals with atherosclerosis risk factors.

Among the possible explanations for this phenomenon is the presence of high levels of asymmetric dimethylarginine (ADMA), an endogenous NOS inhibitor. Higher concentrations of ADMA were encountered in individuals with atherosclerosis, as well as in individuals with atherosclerosis risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus, kidney failure, hyperhomocysteinaemia, smoking and aging [10]. Physiological levels of L-arginine and the presence of normal concentrations of ADMA saturate the endothelial NOS enzyme, promoting NO production. In these conditions, L-arginine supplementation does not affect enzyme activity. In contrast, in the presence of elevated plasma concentrations of ADMA the endothelial NOS activity diminishes, resulting in lower physiological levels of NO production. SDMA has no effect on NOS activity but may compete with L-arginine for the y + transport system [35]. Under these conditions, L-arginine supplementation may re-establish the L-arginine/ADMA ratio in order to activate endothelial NOS [4]. Therefore, L-arginine supplementation may exert a beneficial effect on vascular function."

I would always agree that all the risk factors be taken into account. It's no secret that too much L-Arginine can give you heart palpitations. (I've experienced it myself). The first thing to do is eliminate uncertainty. A fasting amino acid study will show if Arginine is depleted. If it is, ADMA will be excessive as will iNOS. High iNOS is common in MS.

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Re: Reversing Endothelial Dysfunction

Postby cheerleader » Mon May 26, 2014 10:02 am

Hi Scott---Just commenting on what Dr. John Cooke (Stanford researcher, author of The Cardiovascular Cure) told me regarding endothelial health for people with CCSVI---he no longer recommends taking L-Arginine supplements to any of his patients---but recommends holistic lifestyle changes to encourage endothelially derived nitric oxide. There are many foods he recommends to do this-- included in the Endothelial Health Program.

#8 Healthy Proteins--
....Soy proteins produce a mixture of amino acids that have more L-arginine. L-arginine is essential for the production of NO. .... Other L-arginine sources include fish, nuts, legumes, beans and chicken27.

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

It's all about a complete lifestyle. Hope some other people have continued to follow the program-and might chime in. I know it's been 6 years since I first wrote and posted it--lots of people not on the forum anymore.
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Re: Reversing Endothelial Dysfunction

Postby Scott1 » Mon May 26, 2014 12:25 pm

Hi Cheer,

That's a good note. I agree with what you wrote, particularly about lifestyle. We are on the same page. It's just I am happy to supplement as I think we have problems with megalin, ebv, peroxynitrite and glyceraldehyde 3 phosphate (per my note elsewhere) that overwhelm good living alone. It will be question of degrees I suppose. I have found the L-arginine very beneficial but I wouldn't think it's an answer on it's own. I'm comfortable that it improves vasodilation.
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Re: Reversing Endothelial Dysfunction

Postby cheerleader » Mon Jun 16, 2014 4:00 pm

A multi-disciplinary team of researchers from Columbia University has found that vascular endothelial cell dysfunction affects cerebral blood flow, and may be involved in neurological diseases that were assumed to be due to neuronal dysfunction.
http://engineering.columbia.edu/columbi ... blood-flow

"Our latest finding gives us a new way of thinking about brain disease—that some conditions assumed to be caused by faulty neurons could actually be problems with faulty blood vessels”

“Once we realized the importance of endothelial signaling in the regulation of blood flow in the brain,” Hillman adds, “we wondered whether overlooking the vascular endothelium might have led researchers to misinterpret their results.”

Dr. Hillman has spent the past 10 years using advanced medical technology, to study how blood flow is controlled in the brain. Her research team was comprised of a multi-disciplinary members. Other lab members who assisted with the study included PhD and MD/PhD students from Columbia Engineering, Neurobiology and Behavior, and Columbia University Medical Center. The group combined their engineering skills with their expertise in neuroscience, biology, and medicine to understand this new aspect of brain physiology.

To tease apart the role of endothelial signaling in the living brain, they had to develop new ways to both image the brain at very high speeds, and also to selectively alter the ability of endothelial cells to propagate signals within intact vessels. The team achieved this through a range of techniques that use light and optics, including imaging using a high-speed camera with synchronized, strobed LED illumination to capture changes in the color, and thus the oxygenation level of flowing blood. Focused laser light was used in combination with a fluorescent dye within the bloodstream to cause oxidative damage to the inner endothelial layer of blood brain arterioles, while leaving the rest of the vessel intact and responsive. The team showed that, after damaging a small section of a vessel using their laser, the vessel no longer dilated beyond the damaged point. When the endothelium of a larger number of vessels was targeted in the same way, the overall blood flow response of the brain to stimulation was significantly decreased.

The researchers damaged the endothelial layer of cells, causing oxidative stress. After this damage, the blood vessel was no longer able to dilate past the damaged point. This process restricted blood flow to the neurons.

http://ccsviinms.blogspot.com/2014/06/c ... e-new.html

Oxidative stress is only one means of creating endothelial dysfunction. For the full list, plus ways to counteract endothelial dysfunction, and potentially restore normalized blood flow to the brain--
http://www.ccsvi.org/index.php/helping- ... ial-health

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Re: Reversing Endothelial Dysfunction

Postby Scott1 » Tue Jun 17, 2014 3:18 am

What a wonderful opportunity to look at iNOS in that circumstance. They created the perfect situation to give rise to abnormal levels to see what it was doing and completely missed the opportunity. The way I look at it they couldn't see the forest for the trees. Oh well!
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Re: Reversing Endothelial Dysfunction

Postby cheerleader » Tue Jun 24, 2014 8:33 pm

Here's the complete paper from Columbia Un., Scott---
This study is focused on the vascular endothelium and blood vessels' response to oxidative stress. The researchers wanted to understand how this affects cerebral blood flow and neurovascular coupling. Vasodilation is dependent on eNOS and prostanoids. Endothelial health is essential for good blood flow.

It's actually a ground breaking study, because the previous model was that neurons and neuronal stimulus controlled blood flow. Neurologists have said that hypoperfusion in MS occurs because damaged neurons do not require as much blood flow. But these researchers showed how the vascular endothelium initiates blood flow, and neuronal dysfunction may be created by hypoperfusion.... They've turned the current neurological paradigm of cerebral blood flow initiation upside down. It's the damaged blood vessels that come first!

If both slow and fast endothelial pathways (as described above) are involved in functional hyperemia, then, as shown in Figure 5, components of stimulus‐evoked vasodilation would be dependent on both endothelial‐derived NO and prostanoids generated by endothelial COX pathways. Equally, endothelial hyperpolarization‐mediated vasodilation, which is unaffected by COX and NO inhibition, would remain.22 No previous neurovascular coupling studies have attributed a loss of attenuation of vasodilation under COX or NO inhibition to action on the vascular endothelium.7 We propose that endothelial involvement in neurovascular coupling can explain many of the seemingly complex and paradoxical effects of these agents on functional neurovascular coupling, including the presence of residual responses.


In this study, we disrupt the vascular endothelium of cerebral arteries in vivo and demonstrate that this disruption halts retrograde propagation of vasodilation during stimulus‐evoked functional hyperemia. We further show that wide‐field disruption of the endothelium of superficial arteries can profoundly alter functional hemodynamics in the cortex. These findings suggest that the vascular endothelium is a critical component of the functional hemodynamic response to somatosensory stimulus in the living brain.

http://jaha.ahajournals.org/content/3/3/e000787.full

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Re: Reversing Endothelial Dysfunction

Postby vesta » Sun Jul 13, 2014 6:51 am

Thanks cheerleader for re-opening this subject which I missed the first time around. I quoted it in my Blog and am delighted to think it confirms my basic thesis, that childhood stress and an unhealthy lifestyle can actually "deform" the vascular system. If you don't agree with the following quote, let me know. Thanks again. Vesta

"I am pleased to think that my latest readings have validated my theory – that childhood stresses and deficiencies can actually deform the vascular system in the growing future MS child. Joan Beal – cheerleader on the Thisisms.com website, has been preoccupied with the endothelium, that is to say, the inner walls of the vascular system, ever since her husband Jeff underwent successful angioplasty for CCSVI at Stanford in 2009. It was her posts on Nitric Oxide and the Sun which provided the electroshock for me. (I confess I’ve been a bit slow to pick this up.) The Sun provides not only Vitamin D but it promotes Nitric Oxide release as well. And Nitric Oxide is critical to development and function of the vascular system (among other things). And contrary to what Neurologists generally believe, it is not the nerves which impact the blood flow so much as the blood flow which impacts the nerves. It is recent research by scientists preoccupied with cardiovascular disease (not CCSVI or MS) which uncovered these findings. Joan Beal stresses the need of a healthy life style (diet, supplements, exercise, meditation, 10 to 15 minutes of sun daily etc) to maintain a properly functioning endothelium so critical to blood circulation. But if this optimal lifestyle is lacking during the childhood growth period, doesn’t it logically follow that the circulatory system will fail to develop correctly? Lack of sunlight could lead to Vitamin D AND Nitric Oxide deficiencies which might well deform the veins just as rickets deforms the bones. "

From MS Cure Enigmas.net
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Re: Reversing Endothelial Dysfunction

Postby Scott1 » Sun Jul 13, 2014 12:32 pm

I'm not sure you should say "Nitric Oxide deficiencies". It's probably safer to say the wrong form of nitric oxide synthase. iNOS is known to be elevated in MS but I haven't seen anything that says nitric oxide is deficient. I'm not sure how you would measure nitric oxide levels across an organism either.
The topic of sunlight is interesting. The normal association is with Vitamin D but if we break it down to UV light then a whole range of things open up to look at. UV light is something that can activate a range of chemical processes.

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Re: Reversing Endothelial Dysfunction

Postby vesta » Tue Jul 15, 2014 1:59 am

Thanks Scott1: I confess I haven't studied in detail the issue, counting on cheerleader's links to studies on UV rays and nitric oxide and the vascular system. I'm in France and yesterday was Bastille Day so I haven't been working, hence my delayed response. I'm excited to think that getting more sunlight/UV rays in the winter will have a positive effect on me. Since 1966 I've noticed that by February my energies decline and March is always a difficult month. So this year I'm going to really try to get the 15 minutes? of UV rays daily and see if that makes a differrence. What kind of lamp would you recommend for the UV rays? Do you disagree with cheerleader on this issue? (Her input has been extremely beneficial for me.) Sometimes a single idea can make a huge difference. Ever since I read about the blood circulation theory (Zamboni) of MS summer 2010, I began non invasive therapies to keep the "fluids" flowing which has changed my life. I began to limp after a stress event May 1992 and it makes me "ill" to now realize that a simple neck massage pushing the blood out of my head could have stopped it. Well, better late than never. Maybe the UV issue will help a bit more. Regards, Vesta
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Re: Reversing Endothelial Dysfunction

Postby Scott1 » Wed Jul 16, 2014 12:28 pm

Hi Vesta,
In Australia we are learning to stay out of the sun because of the very real risk of skin cancer. We have enough sunlight so I can't even imagine why I would use a UV lamp. MS is well known here so UV can't be the major issue. UV can activate certain chemical processes. For example, some industrial glues won't cure unless a UV light is applied. If you get a benefit then I would say you can't dismiss the idea that something is happening. They are treating Vitiglio with creams that are activated by UV. There is a correlated increase in Vitamin D after exposure to sunlight but as I have noted in other posts I don't think it means much unless you elevate the nuclear receptor RXR as that is the master switch for VDR. They act in a complex, not alone.
By all means get a bit more UV when the days are short but be careful. I don't think it will be the answer. Tanning salons in some states in Australia are now regulated because people have died due to too much UV. I doubt chasing a number for Vit D will help much either. It is the sum of all the things we do that makes a difference.

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Re: Reversing Endothelial Dysfunction

Postby cheerleader » Thu Jul 17, 2014 2:22 pm

Vesta's got it. UV is essential for human life and health--not only for vitamin D but for vascular health and endothelially derived nitric oxide, Scott. Of course, it is only one aspect of endothelial health, but it is an important one.

Sunshine avoidance doubled mortality rates in a recent Swedish study, which set out to look at melanoma rates and instead found out that sun avoidance was much more dangerous.
The results of this study provide observational evidence that avoiding sun exposure is a risk factor for all-cause mortality. Following sun exposure advice that is very restrictive in countries with low solar intensity might in fact be harmful to women's health.

http://onlinelibrary.wiley.com/doi/10.1 ... 1/abstract

Here is my mentor on this topic, and the researcher who sent me the full paper for that recent Swedish study, Dr. Richard Weller--
http://scholar.google.com/citations?use ... AAAJ&hl=en

Take ten minutes and watch his TED presentation. He's a brilliant man, and he's now going to be looking at UV, NO and MS. Yay!
https://www.ted.com/talks/richard_welle ... your_heart

and here is some of what I've written about UV and MS---links to peer-reviewed research are always included on my blog.
http://ccsviinms.blogspot.com/2013/06/p ... -june.html

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