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Re: Reversing Endothelial Dysfunction

Posted: Fri Jul 18, 2014 4:09 am
by Scott1
Hi Cheer,

I have no doubt UV is important. It's just in Australia we have an abundance of it yet the issues we are dealing with still persist. There has to be more to it so the issue you are dealing with will be about how UV can disrupt the cause of veinous narrowing rather than lack of UV being the cause. Why there is problem with Nitric oxide dilating blood vessels would be the question for me.
The Swedish study describes an almost impossible scenario in Australia yet we have plenty of examples of MS.


Re: Reversing Endothelial Dysfunction

Posted: Fri Jul 18, 2014 8:06 am
by THX1138
When it comes to Reversing Endothelial Dysfunction, I believe that Magnesium plays a larger role than people are led to believe by lab tests. Magnesium is difficult to measure properly and the most common test will usually mislead both doctors and patients:
The underestimated problem of using serum magnesium measurements to exclude magnesium deficiency in adults; a health warning is needed for "normal" results.

Magnesium is a vasorelaxant.

Just the other day I had a revealing experience with Mg:

Re: Reversing Endothelial Dysfunction

Posted: Sat Jul 19, 2014 10:43 am
by cheerleader
Scott--Please watch Dr. Weller's video---he explains UV rays and how they release NO from dermal storage better than I ever could. His studies were done on humans, and he has vitally important information. I never said it's a cause...I said it is one important component. He discusses Australia, as well. You can have great sun and UV, but spend all day indoors and never get UV, and that's a problem. Honest, it's worth 10 minutes.

But reversing endothelial dysfunction is multi model. It involves nutrition, exercise and lifestyle. What we eat, breath, and how we live.

Yes, Mg is incredibly important, yes, UV is important, too. But so is moving every day (to create vascular shear stress), reducing stress (to reduce cortisol), not smoking (a known vasoconstrictor), not eating transfats (damaging to endothelial cells), not eating processed foods or too much sugar. Sleep is essential, laughter helps. Vitamin D and B12 are necessary. We are complex organisms. Never going to be about one pill, one supplement, one adjustment or one size fits all. It is about a complete, individualized lifestyle. Every day.

Here's the whole program. It works. But it takes work. ... ial-health


Re: Reversing Endothelial Dysfunction

Posted: Sun Jul 20, 2014 12:57 am
by Scott1
Hi Cheer,

I have no argument with anything you have said except I would start earlier in the process. The post I put up a couple below this one also highlights the role of megalin in Vitamin D transport, the role of the retinoid X receptor, how ADMA influences nitric oxide synthase and how superoxide combines with nitric oxide to make peroxynitrite.
It's fascinating how UV helps vasodilation. It also works against hydrogen peroxide and peroxynitrite. I agree it's a multifaceted thing.
My only issue is the question of Vitamin D itself. Undoubtedly it's important but I'm a bit concerned it gets an elevated status it might not deserve. It feels to me that when serum Vitamin D is elevated the outcomes are not consistent and in a large part of the healthy population the level cycles with sunlight but no adverse affect generally arises as the level falls. I'm sure the UV helps and I agree vasodilation helps, I'm just not so sure about Vitamin D. It might be the politician in the office rather than the genuine worker. I never worry about Vitamin D but I obsess about vasodilation, mitochondrial respiration and activating RXR and I'm very well. I did work very hard on EBV because it caused the expansion of superoxide but I think I won that war after a decade.
Happy to be proven wrong as I still think it's the sum of things that matters.


Re: Reversing Endothelial Dysfunction

Posted: Sun Jul 20, 2014 8:48 am
by cheerleader
Did you watch the video, Scott?

Dr. Weller explains that vitamin D levels may purely be a biomarker of UV exposure.
Many benefits of sunshine are outside of Vit. D creation. Which is why supplementing vitamin D isn't enough.
Watch the video, Scott...we're saying the same thing :) Honestly.

Nitric oxide (NO) does more than dilate vessels---it also protects organs, stimulates the brain, kills bacteria and viruses ... press.html
I'm not here to "prove" anyone wrong...just trying to bring to light some fascinating research on how UV affects the human body, outside of vitamin D, by releasing NO stores from the skin. And maybe encourage people to go outside and get some sun. We do that everyday in southern Cal.
Here is a recent paper from BNAC which looked at sunlight exposure and brain volume on MRI in people with MS. They did not look at NO--but Dr. Weller is proposing a new study to do just that. This is all new research....

Increased summer sun exposure was associated with increased grey matter volume
(GMV, r(p)=0.16, p=0.019) and whole brain volume (WBV, r(p)=0.20, p=0.004) after correcting for Extended Disability Status Scale in the MS group. Inclusion of 25-hydroxy vitamin D3 levels did not substantially affect the positive associations of sun exposure with WBV (r(p)=0.18, p=0.003) and GMV (r(p)=0.14, p=0.026) in the MS group.
Sun exposure may have direct effects on MRI measures of neurodegeneration in MS, independently of vitamin D.
from my blog on Vitamin D status and 5 Year MS Study ... study.html

Re: Reversing Endothelial Dysfunction

Posted: Mon Jul 21, 2014 12:42 am
by Scott1
Hi Cheer,

I agree. We are in enthusiastic agreement.

I did have a problem watching the video thanks to a faulty windows 8.1. All fixed now.

The vitamin D is processed in the renal proximal tube and that is a long way from direct sunlight. There is clearly a chemical process in the skin activated by sunlight which is quite fascinating. Also,don't forget you need nitric oxide to make peroxynitrite. That's the bad guy in my view and it needs an abundant supply of superoxide to combine with nitric oxide. Nitric oxide is a good guy but it needs eNOS and nNos working not iNOS.

For a example of how using UV can break down the influence of radicals in the skin have a look at this - ... 9.full.pdf

The pictures are striking.

For an example of the damage peroxynitrite can do read this -

UV has a real role to play.


Re: Reversing Endothelial Dysfunction

Posted: Tue Dec 02, 2014 10:38 am
by 1eye
*********************************** my $0.02 on LDN, UV ABC *********************************************

From what I have read (not from anything scholarly) LDN increases angiogenesis. That can be good (if you need new collateral veins, for instance) or bad (if your cancerous cells need a blood supply). It also increases follicle stimulating hormone (FSH) and leutenizing hormone (LH) levels, and here I have some experience. From my brief encounter with LDN I found my hair and nails changed and became somewhat healthier. Take this with as much NaCl as you wish. The theory of its health benefit is based on its opiate-blocking in high doses. The low dose, if timed right, should make your own endorphin production to increase, in a rebound effect, hours after the short block is over.

High energy UV light (UVB and UVC) are the components of sunlight that may cause cancer. It is completely random (a mutation) but exposure increases your chance of a mutation. The UV that Weller spoke about was UVA, which is lower in energy and has less chance of causing cancer. If you get the UVA (even from a lamp, like a "black-light") you still get the heart/endothelial benefit.

For the Vitamin D skin production it takes UVB, and again prudence is warranted, especially in areas where lots of sun is already available, because of the increased cancer risk.

***********************************back to the nitric oxide discussion **********************************************

I have a notion that something is being overlooked.

There is much concern over nitric oxide because of its role in vasodilation. I suppose that if you have a stenosis, dilation of unstenosed vessels can help that somewhat. If you have a cooling problem, dilation is necessary. It is suspected that chronically over-dilated vessels can lose their tone and become unresponsive to nitric oxide, which may be present in overabundance in "MS".

Doesn't endothelial health depend on targeted dilation, when and where it is required? This, I think, is where eNOS comes in. The effect of eNOS is smaller, and more precise. Nitric oxide, if dissolved in blood in enough quantity, is present everywhere, and iNOS seems to have a much larger, global effect, on more, if not all, vessels.

Surely we must have something equivalent to nitric oxide, present in small, targeted amounts like what you get from eNOS, and large, global amounts, like what you get from iNOS, that causes the opposite effect? So that we can precisely control both vasodilation and, where warranted, vasoconstriction? If I had two such substances, neither too scarce, nor too over-abundant, then I could control my vessel diameters, and be responsive to both kinds of signals, keeping smooth muscles in good working tone.

So what is the signalling equivalent of nitric oxide, when it comes to vasoconstriction? I know coffee is habitual, and I get terrible vasoconstriction headaches when I stop using it. But what is the normal vasoconstrictive substance, signal, or other mechanism?

Re: Reversing Endothelial Dysfunction

Posted: Tue Dec 02, 2014 11:33 am
by cheerleader
Hi 1eye--
I started this thread way back when to discuss ways to improve endothelial health.
I am certainly not a biologist or scientist...I went to Dr. John Cooke to find ways to improve Jeff's vascular health and CBC numbers (he had high SED rate, ESR, c reactive protein, liver enzymes, hypercoagulation), and then I shared them online.
Here's a well-written recent scientific article on eNOS and endothelial health. ... ticle/2185
eNOS is activated by physiological and metabolic stimuli, shear stress, and receptor-dependent agonists to functionally inhibit platelet aggregation, leukocyte adhesion, and smooth muscle cell proliferation, as well as to maintain vascular tone. Oxidative stress uncouples eNOS-derived NO, increasing ONOO- production, which leads to endothelial dysfunction.
If you read the Endothelial Health program, you'll note that the #1 factor I listed in endothelial dysfunction is oxidative stress--leading to this uncoupling, iNOS build up and disease. I give lists of environmental factors which increase oxidative stress, including plastics, diesel fuel emissions, homocysteine, toxins, heavy metals, smoking....many things in our modern lifestyles increase oxidative stress. The way to avoid endothelial dysfunction include avoidance of the oxidant inducers, and increasing antioxidants, exercise created shear stress, whole foods full of phytonutrients, minerals, stress reduction, etc. -----the Endothelial Health program. ... ial-health

We do know that endothelial health is a sign of cardiovascular health. eNOS is part of this equation. But eNOS does more than vasodilate---it kills bacteria, protects organs and stimulates the brain. The endothelium is the meeting place of the vascular and immune systems, which is why it interested me in the first place. Endothelial health is much more than vessel dilatation.

Vasoconstriction is mediated by calcium channels within smooth muscle cells.
Coffee's caffeine is an external activator of this process. Caffeine withdrawal headaches are due to increased blood flow.

Not a doctor Cheer

Re: Reversing Endothelial Dysfunction

Posted: Tue Dec 02, 2014 1:38 pm
by Scott1
The other thing to remember is iNOS is a natural response by the body when other forms of NOS are unavailable. It is a response to injury. So that's why we see it elevated in the MS cohort. One way it arises is from oxidative stress. Another way is if the kidney produces Asymmetric dimethylarginine (ADMA) rather than the symmetrical form. ADMA scavenges all NOS isoforms so the body will respond as if injured and make iNOS as a response.
iNOS is structurally different to the other forms. (see- ... /mechanism )
There's a lot of moving parts. Taking L-arginine should help overcome the effect of ADMA but obviously doing many of the other things noted that are antioxidative will help as well.
How well the cell respires will drive outcomes as well. That influences the electron transport pathway which impacts how we use oxygen. It is not easy to patch together.

Re: Reversing Endothelial Dysfunction

Posted: Wed Dec 03, 2014 9:13 am
by cheerleader
I understand how iNOS is created, and that it's multi-factorial. It is called in during injury, infection, stress, etc. What I was saying is that one way it is created is uncoupling of eNOS, due to oxidative stress, and this is something that can potentially be addressed, by mitigating external environmental factors. My theory since Jeff's diagnosis in 2007 is that MS is a disease that contains aspects of vascular endothelial dysfunction. And since this thread started, more MS researchers are looking into this correlation. ... id=8297195

We've already gone back and forth on L-arginine on page 11 of this thread, but I'll say it once again.
The reason I didn't include L-arginine in the endothelial health program is because Dr. John Cooke does not recommend L-arginine to his patients. Long term it did not help increase eNOS in a study he conducted, in fact it had an opposite effect after long term use. ... 91207.html

Because of this, he recommends diet, exercise, smoking cessation, lifestyle changes, supplements, and letting the body produce its own eNOS precursors. I talked about this with him at length. I trust him--the premiere endothelial specialist in the US, who is now creating new endothelial cells from fibroblasts. He was kind enough to meet with us, and helped get Jeff treated for CCSVI and work on an aftercare program. ... /81250576/

The program works in addressing external/environmental factors in endothelial dysfunction, which may contribute to MS. ... ial-health
Reading this thread from the beginning is pretty good...we cover LDN, caffeine, vasodilation, L-arginine. And also the beginning of the CCSVI discussion on ThisIsMS.

Re: Reversing Endothelial Dysfunction

Posted: Thu Dec 04, 2014 12:19 am
by Scott1

Hi Cheer,
I think we are talking at cross purpose here. John Cooke is looking at the effect of long term use of Arginine on atherosclerosis in peripheral arterial disease particularly in the legs. He has done a 180 degree turn on its usefulness in that context. That’s fine.
I mentioned oxidative stress as one thing to look at but I want to put my emphasis on the relationship with ADMA.
This article seems to be protected from copying and pasting (at least for me!). Section 1.3 talks about ADMA uncoupling NOS.
Figure 1 illustrates ADMA blocking L-Arginine.
I get all the healthy lifestyle stuff but ADMA doesn’t always need an oxidative trigger.

Re: Reversing Endothelial Dysfunction

Posted: Wed Jul 01, 2015 6:45 am
by cheerleader
Since the discovery of lymphatic vessels in the brain, good to know that endothelial cells line our lymphatic vessels, as well as blood vessels. Endothelial cells moderate how lymph is distributed throughout the body and removed. They provide the interface between vessels and tissue, and endothelial dysfunction can create problems. Nitric oxide appears to have the same regulatory function on lymph, as it does in blood vessels, by allowing or inhibiting permeability in inflammatory situations.

I included lymph vessels in the Endothelial Health Program for this very reason, even though when I wrote it, we didn't know lymph traveled into the brain. All of the measures used to help blood vessels apply to lymph vessels, as well. There are many ways to address inflammation, oxidation and endothelial cell dysfunction and raise NO levels with lifestyle, nutrition and supplements. ... ial-health


Re: Reversing Endothelial Dysfunction

Posted: Thu Jul 16, 2015 2:09 pm
by cheerleader
New research finds endothelial microparticles, or EMPs--which are shed by dying and diseased endothelial cells-- in the serum of pwMS. EMP levels correlated with lesions and brain atrophy on MRI. These microparticles are NOT found in normal people, and are a sign of endothelial dysfunction.
We have a brand new peer-reviewed paper from the researchers of the ISNVD which is considering the vascular connection to MS. It is called:
"Blood circulating microparticle species in relapsing–remitting and secondary progressive multiple sclerosis. A case–control, cross sectional study with conventional MRI and advanced iron content imaging outcomes" This paper is published in the Journal of Neurological Sciences. ... 3/abstract
read more: ... se-of.html


Re: Reversing Endothelial Dysfunction

Posted: Sat Oct 10, 2015 10:41 pm
by CureOrBust
Just stumbled across this page and thought I would add it to this post. Sorry if its already been covered. ie regarding Folate. The page has references to the studies from which the statement is based. ... ar-disease
Endothelial function: Folic acid has been shown to prevent postprandial endothelial dysfunction in normohomocysteinaemic subjects, and to improve endothelial function in patients with hyperhomocysteinaemia, hypercholesterolaemia, diabetes and coronary artery disease.3 The exact mechanisms underlying the ameliorative effects of folate on the endothelium are uncertain, but may include homocysteine-lowering, antioxidant actions, effects on cofactor availability, or direct interactions with the enzyme endothelial nitric oxide synthase.11-13

Re: Reversing Endothelial Dysfunction

Posted: Mon Oct 19, 2015 6:23 pm
by cheerleader
Yup. Homocysteine and B12 are in the Endothelial Health Program. ... ial-health
Low vitamin B12 creates high levels of homocysteine in the blood (a sulfur containing amino acid) which damages the endothelium. An unbalanced diet, a strict vegetarian diet that excludes all meat, fish, dairy and eggs diet, or a diet overly reliant on processed foods, could all lead to low vitamin B12 levels, potentially damaging the endothelium20.
Thanks, Cure.