Endothelin 1-- More vascular evidence

In the news--- Newly discovered peptide, blocks remyelination!!   Stopping this process repairs MS damage.  
http://www.natureworldnews.com/articles/5951/20140208/study-identifies-protein-inhibits-brain-tissue-repair-ms-patients.htm

What's this "new" peptide we want to block?   
It's called endothelin-1 or ET-1, and it's released by the astrocytes maintaining the endothelial layer of your blood brain barrier.
http://www.cell.com/neuron/abstract/S0896-6273(13)01083-0

We've known about ET-1 for years.  It's not only found in MS.
Endothelin-1 is raised in situations where there is endothelial distress.  When endothelial cells are hurt by ischemia and oxidative stress, and nitric oxide levels are low.  ET-1 creates vasoconstriction,  is pro-inflammatory, pro-fibrotic and slows blood flow.  Which would explain why it inhibits remyelination. Yet not one single press release on this exciting new MS discovery mentioned this important fact, or what causes ET-1 levels to be high in the first place.

As you might expect, plasma ET-1 levels are very high in ischemic stroke.
http://stroke.ahajournals.org/content/23/7/1014.full.pdf

ET-1 released by astrocytes is seen after subarachnoid hemorrhage
http://www.biomedcentral.com/1471-2202/14/131

Serum levels of ET-1 are used as a marker of cerebral ischemia
http://www.intmed.ro/attach/rjim/2010/rjim410/art06.pdf

And Endothelin 1 serum levels are through the roof in people with MS----

The plasma ET-1 levels were, on average, 224% higher in the patients with MS than in the controls (p < 0.005). The mean ET-1 levels (mean +/- standard deviation [SD]) were 3.5 +/- 0.83 pg/mL (min 2.13, max 5.37 pg/mL) in patients with MS and 1.56 +/- 0.3 pg/mL (min 0.9, max 2.13 pg/mL) in healthy volunteers. Neither the different forms nor stages of MS had an influence on the results. The ET-1 level was also not correlated with the duration of the disease.
http://www.ncbi.nlm.nih.gov/pubmed/11315981

In fact, researchers have been looking at ET-1 for many years.
Here are some MS researchers that found that hypoperfusion in MS was related to ET-1 levels.  They used an ET-1 inhibitor called Bosentan, which increased cerebral blood flow.  (Bosentan is a high blood pressure medicine, which can be toxic to the liver.)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619305/

Why are MS researchers reticent to fully explore  the connection of extracranial venous obstruction to hypoxic/ischemic conditions in the brain?   I'm sure I don't need to reiterate this, but this ET-1 "breakthrough" may well be caused by Dr. Zamboni's discovery of restricted venous return.

The truth is, the best way to lower ET-1 levels might be to increase nitric oxide levels yourself.
High ET-1 levels are a sign that your nitric oxide supply is too low.
http://www.ncbi.nlm.nih.gov/pubmed/21368267

While we are waiting for that Breakthrough Drug! ™ 
here are some things you can do for free, on your own, to potentially increase your cerebral perfusion, remyelinate your brain, raise your NO levels and lower your ET-1 levels.



EXERCISE 
The present study suggests that exercise causes an increase in production of NO and a decrease in production of ET-1 in humans, which may produce beneficial effects (i.e., vasodilative and antiatherosclerotic) on the cardiovascular system.
http://www.sciencedirect.com/science/article/pii/S0024320501011924


EAT MORE FLAVONOIDS (fruits and veggies)
Epidemiological evidence demonstrates that diets rich in fruits and vegetables benefit heart and vascular health.(2–11) Molecularly, these beneficial effects of fruits and vegetables have been largely ascribed to their content in flavonoids. These compounds are synthesized in many edible plants and remain present when plants are processed to foods. Grapes and wine, cocoa and chocolate, black and green tea, and soy and soy-derived products, are among the most important sources of flavonoids in the human diet.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022066/

Dietary flavonoids, such as quercetin and (-)-epicatechin, can augment nitric oxide status and reduce endothelin-1 concentrations and may thereby improve endothelial function.
http://www.ncbi.nlm.nih.gov/pubmed/18842789


EAT MORE POLYUNSATURATED FATS (from nuts, seeds and fish)
Serum levels of ET-1 were positively correlated with saturated fatty acids (SFAs, r = 0.257; P = 0.025) and negatively correlated with polyunsaturated fatty acids (PUFAs, r = -0.319; P = 0.005). http://www.ncbi.nlm.nih.gov/pubmed/18702940

WATCH YOUR WEIGHT

These results demonstrate that overweight and obesity are associated with enhanced ET-1-mediated vasoconstriction that contributes to endothelial vasodilator dysfunction and may play a role in the increased prevalence of hypertension with increased adiposity.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191085/


Here are some more ideas on how to address endothelial dysfunction.  Always discuss any new health regimen with your own physician.
http://ccsvi.org/index.php/helping-myself/endothelial-health


There are things we can control, and things we can't.
There are ways to boost your nitric oxide levels, lower you ET-1 levels and potentially improve your health.  While researchers continue to look for ways to mediate the vascular connection to MS without mentioning or exploring the vascular connection to MS....
take control.

Joan

ISNVD 2014--the big picture

Jeff and I are home from the intense sessions at the fourth annual International Society for Neurovascular Disease (ISNVD) conference.  We both commented that it was like being back in college---the amount of information presented was impressive and challenging, and by the end of the day, our brains were quite literally fried.  We are very thankful to Dr. Michael Dake, the current president of this group, for allowing non-medical folks (I call us the "laity") to sit in on the presentations.  It is very informative for those of us with "skin in the game" to hear where the research is going.

I had a chance to sit down with Dr. Paolo Zamboni and discuss the developments of the past five years.  It was September 2009, when we first met and talked about CCSVI research, at the Bologna conference.  Much has changed since that time, yet one fact remains the same---

We know that the extracranial venous system contributes to neurodegenerative disease, and in many cases, venoplasty to relieve CCSVI can improve neurological symptomology, by increasing cerebral perfusion and cerebrospinal fluid flow.

For those waiting for venoplasty treatment, the progress has been painfully slow, full of delays and frustration.  (The FDA approval of the Hubbard Foundation CCSVI registry is one beacon of good news!)  While many of these delays have seemed like simply a waste of time, some of the delays have helped the researchers understand the larger picture of cerebral hemodynamics--and the skeletal, muscular and truncular venous malformations which may contribute to restricted venous return.

We now know that CCSVI can affect those with Parkinson's and other neurodegenerative diseases.  This is not simply a problem in multiple sclerosis.  The diversity of specialties represented by the conference faculty was indicative of this change.  There were specialists in Alzheimer's research, traumatic brain injury, migraine,  panic attacks, stroke, TIA, and other neurovascular conditions.  All spoke of the vascular connection to their research, and the importance of the venous side of blood flow.  The jugular veins got a lot of attention---something that is a new development, thanks to Dr. Zamboni!

Participants heard research presentations on the cellular level of the endothelium in Alzheimer's disease process, where endothelial dysfunction begins prior to amyloid plaque formation.  Endothelial dysfunction is also implicated in the vascular connection to MS, where an increase of iNOS and a break in the blood brain barrier leads to inflammation and neurodegeneration.

There are still debates as to how to treat CCSVI--whether venoplasty is the best or only way.  I had a few opportunities to discuss the importance of lifestyle with Dr. Paula Grammas.  I first reached out to Dr. Grammas after reading her impressive research on endothelial dysfunction in Alzheimer's Disease.  Dr. Grammas considers the beta amyloid plaques, which have become the only focus of Alzheimer's research, to be a potential symptom of a larger problem--the miscommunication of endothelial cells.  I introduced her to the ISNVD, and was so pleased to hear her give the keynote presentation this year.

Dr. Grammas is a warm and thoughtful woman.  She was a pleasure to talk to. We discussed the anti-angiogenesis drugs that she will be looking at in clinical trials.  But we also discussed "the things we can change" today, in our own lives, without needing a prescription.  There are many known cardiovascular factors which increase our risk for dementia--including smoking, obesity, high cholesterol, inactivity, and stress.  And the best thing we can do for ourselves and our brains is maintain a healthy weight, eat a whole food diet, full of phytonutrients, move every day, not smoke, and reduce stress.  We also talked about the fact that healthy living is not about a "cure" for disease, but a means of prevention of disease progression.  The old adage, "an once of prevention is worth a pound of cure", is being proven in labs around the globe.

It was great to reconnect with friends who are patients and advocates.  The efforts of volunteers like Carol Schumacher and Sharon Richardson cannot be praised enough.  The doctors are always happy to see their patients---Dr. Dake was thrilled to see Jeff doing so well, and to hear him playing his trumpet at the ISNVD Gala.  It was a pleasure to see our Canadian friends--including journalists Avis Favaro and Anne Kingston.

I was thankful to have Jeff with me---for him to see the part of my world and work that has consumed much of my free time during the past five years.  As a friend commented, this research isn't "really his thing."  He is thankful for it, but it hasn't preoccupied him in the same way.  However, Jeff was touched and honored to sit with Dr. Zamboni, to hug and visit with other people with CCSVI, and to meet so many of the doctors who are changing the paradigm in neurovascular research.  I am thankful every day for his renewed energy, health, and our ability to travel together.  As I huffed and puffed, climbing those famous San Francisco hills, struggling to keep up with Jeff on our brisk daily walk...I marvelled at his health, and recommitted myself to helping other people with MS find hope and healing.

Joan

Newly diagnosed are healthier today than a decade ago

Dr. Lawrence Steinman recently made a very interesting comment in an article on vitamin D levels in MS progression. (Dr. Steinman, MS researcher and inventor of Tysabri, is now behind the upcoming clinical trial of Lisinopril, an inexpensive generic blood pressure medication, as a treatment for MS.)
 http://ccsviinms.blogspot.com/2013/08/medications-for-ms-addressing-blood.html

Dr. Steinman noted that there has been a decrease in relapse rates in the placebo end of MS drug trials over the last decade.


"I might wonder if these data might explain the progressive decrease in relapse rate in the placebo arm of clinical trials of MS over the past decade. Maybe more and more individuals are aware of vitamin D, and that they are taking vitamin D supplements, thus lowering the relapse rate in placebo arms of trials."
http://www.medpagetoday.com/Neurology/MultipleSclerosis/43899

That's right.
People who are diagnosed with MS today are having less relapses than people diagnosed a decade ago---without being on a disease modifying drug.  These patients were in the placebo end of trials, and not getting the real medication.

What does this mean?  I believe it means the self-help, or "alternative" information is getting out there, thanks to the internet.  People with MS are sharing information, and getting healthier.

When Jeff was diagnosed seven years ago,  I asked his neurologist to test his Vitamin D3 levels.  I had been reading research on Dr. Ashton Embry's website, Direct MS, http://www.direct-ms.org  and wondered about the correlation.  His neurologist said it didn't matter.  Neither did diet or exercise.  MS was an immune-mediated degenerative disease, and there were no scientifically proven means, aside from disease modifying drugs, to slow disease progression.  Case closed.  Good luck.

We got Jeff's GP to order the test, although we had to pay for it, since our insurance didn't cover vitamin D testing.  Sure enough, his level was very low at 15ng/mL  He began to get more sunshine exposure, and take a D supplement w/magnesium and zinc, and the next time he was tested, six months later, his level was at 70ng/mL.  He felt better, too.

And today, we have research showing that Vitamin D levels really do make a difference.  So important, that it is now part of my insurance's paid complete blood testing.  This is new!

But I would submit that it's not just about Vitamin D.

We also have Dr. Terry Wahls, Dr. David Perlmutter, and Dr. George Jelinek sharing their knowledge about nutrition and the importance of a whole food diet and exercise with their large online communities. There are self help groups on websites like This Is MS and Facebook encouraging healthy lifestyles.  Information for newly diagnosed patients now includes nutrition, exercise, Vitamin D, smoking cessation, and stress reduction--and this advice sometimes even comes from the neurologist or the MS Societies.  I hope I've made a small contribution in discussing the endothelium and vascular connection to MS, and by bringing Dr. Zamboni's research to the states and connecting new doctors to the ISNVD.

What a change from only seven years ago!!

When Dr. Roy Swank first noted what he called "capillary fragility" in the 1950s and designed a diet and exercise program to deal with the hypercoagulated blood he found in his MS patients, he was decades ahead of the discovery of nitric oxide and endothelial health.  His patients had fewer relapses and slower MS disease progression in the era before the DMDs.  His contribution to helping MS patients was called "junk science" and he was labled a quack by neurologists.  Yet 60 years later, we see newly diagnosed RRMS patients incorporating whole food diets, vitamin D and exercise--and doing better.

I've said this before, I'll say it again.  Don't wait for your neurologist to tell you that the "science is finally in."  Take your life and health into your own hands today.  Move every day, eat well, get UV rays and supplement D3, laugh and find ways to reduce stress, don't smoke, get a good night's sleep, take care of yourself.

Because in seven years----it may well be a whole new world,
Joan