Setting the record straight

I want to simply state some facts for my readers.  Because if I don't, journalists and bloggers will continue to create a narrative of the kooky singing wife, who found some crazy researcher online and led the world on a goose chase.  And that's not true.  And it's really hurtful.

Some factual, documented history:

1.  I believed there was a vascular connection to my husband's MS diagnosis from day one.  That would be March 23, 2007, the day we got his serum results from the doctor and I saw so many numbers that were way out of normal range.   Coincidently, my birthday.

2.  Using Jeff's serum results as a point of reference, I went to the library and took out every single book they had on MS, including McAlpine's history of Multiple Sclerosis--which had a section on the long history of the vascular connection.  This is where I first read about Dr. Tracy Putnam.  link The pile of textbooks also included Dr. Swank's research.  Dr. Swank wrote about the connection of MS to the blood.  He published over 100 research papers on MS.  He wrote about capillary fragility, petechiae and hypercoagulation in his MS patients--all of this research rang a lot of bells for me.  link

3.  I was on a forum called "This is MS" in September 2007.  I wrote about Jeff's serum results, hypercoagulation, and postulated on a bunch of research with other people with MS and caretakers.  It was a great community, and we shared papers, programs and MS research.

4.  Using pubmed and my local library, I eventually came to the intersection between the vascular and immune system I had been searching for---the endothelium.  Using published and peer-reviewed science, I created The Endothelial Health Program for Jeff and shared it on This is MS in the summer of 2008.   I saw a connection between many of his vascular issues (petechiae, high Crp levels, hypercoagulation, high liver enzymes), endothelial dysfunction, and his MS diagnosis.  We found that by changing his diet to a Swank program, increasing his Vitamin D levels, including cardiovascular exercise, thinning his blood with proleolytic enzymes, getting him out in sunshine, reducing work stress, improving his sleep---he was doing much better, he did not have a relapse and his serum results normalized. http://ccsvi.org/index.php/helping-myself/endothelial-health

5.  I wrote to endothelial researchers at USC and Stanford, asking if they had any knowledge of studies or published research on the function of the endothelium in MS.  Both of them e-mailed me back.   I began a correspondence with the researcher at Stanford, because he was the most interested in this connection.  Here is part of his reply.  I have all of the e-mails, if anyone aside from me ever truly wants to get this story correct.

"I enjoyed reading your treatise. 
I quite like the hypothesis that MS is secondary to a derangement of the endothelium of the cerebrovasculature, that results in inflammation and local damage. 
I am also in agreement with your contention that a functioning endothelium is a major key to health. 
Furthermore, I agree that diet and exercise are critical for endothelial health." 

6.  It would be three months later I would send more research to this doctor.  One of the papers was Dr. Zamboni's new publication on CCSVI, which had been shared with me, the "vascular hypothesis gal" on This Is MS.   He was fascinated by the research, and suggested further testing for Jeff.  Here's part of that e-mail.

  "You could get more evidence for cerebral venous abnormalities (I would be particularly concerned about venous stenoses) by MR imaging, with attention to the cerebral veins. "

7.  We would eventually bring Jeff up to Stanford for TESTING to see if he had any venous abnormalities.  It took a few months to schedule, as he was busy composing and we needed to travel from LA to the Bay Area.   He was tested in April, 2009.   My mistake was that I wrote about all of this online, on the This is MS forum.  I should not have done this.  It is my one, deep regret.  But it is also why I continue to blog and write.  Because I feel hugely responsible for what would later happen.

8.   Jeff had serious venous abnormalities, documented on MRV.  link  He had a 99% stenosis in his left jugular vein and an 80% closure of his right.  The doctor we were consulting with felt this was a serious issue for his brain perfusion, and suggested we think about potential treatment.  We went home.

9.  After consulting with other physicians,  Jeff scheduled his venoplasty treatment for May 2009.  He went back up to Stanford and was treated for his venous abnormalities.  He had a profound response on the table---he felt as though the "lights came on" after a stent was opened on his left side.   He came home and slept soundly, without spasms, for the first time in over a year.  He was dreaming again.  He also had a terrible headache the first day, and would develop severe shoulder pain from having his accessory nerve pinched by stents.  These side effects from the treatment would pass, but it was scary.  Again, I wrote about it online.

10.  People read what I wrote, called Stanford, were treated there or tried to get treated elsewhere.  The press picked it up, and the rest is pretty well documented.  What is never reported correctly is that I didn't force an IR to treat Jeff.   We asked him to TEST Jeff for venous abnormalities.  When we saw how bad they were, the IR suggested treatment,  and we eventually agreed.

I never called venoplasty a cure for MS.  I also never meant for people to get hurt, or travel for medical tourism, spend thousands of dollars (as Jeff was covered by our insurance)  or most terribly, to die from complications.  I certainly didn't want to be labeled the crazed wife who forced an IR to treat her husband.  I always said this was only part of living a vascularly healthy life, to encourage healing and strengthen the heart-brain connection.  I never used the word cure.   I started the Facebook group because I was really concerned with how this research was being discussed as a cure.    link  I was also shocked with how vehemently the MS specialists were denying any link to the vasculature.  I wanted people to know this was only a treatment, and it might not be right for them. Which is partially why I stayed online.   That, and a huge amount of pride, I'm sure.  Ego is never a good thing, and I know it complicated this issue.

But in all honesty, all I wanted were answers for the love of my life.  And we hung around because we had hoped this could be helpful to others.  But to be continually portrayed as cure seekers, zealots and wingnuts by the NY Times, the Wall Street Journal, and other publications (which will live online ad infinitum) and to have our names linked to false and incomplete reporting is simply too much.

So, there it is.

Going for a walk with my love, and our 17 yr. old dog, Angel (another medical anomaly)
Have a nice day,

Joan

BDNF, exercise and the vascular endothelium

Another new paper showing the vascular connection to MS.

New research shows that a 24 week resistance and endurance exercise program increases brain derived neurotrophic factor (BDNF) in people with MS.
link

At baseline, the BDNF concentration of persons with RRMS was 21% lower than healthy controls. Following 24 weeks of intervention, changes in BDNF concentrations differed significantly between exercise group and sedentary group.  In particular, within exercise group, BDNF concentrations increased 13.9% ± 8.8%, whereas it decreased 10.5% ± 4.1% within sendentary group. 

BDNF is called the "Miracle-Gro" for the brain.  It is a very important cerebrovascular protein which protects neurons and allows for neurogenesis, or the growth of new neurons.  BDNF is vital to learning, memory and executive function.

Lower levels of BDNF are linked to Alzheimer's, dementia, depression, diabetes---and now, Multiple Sclerosis.

Cardiovascular researchers have known that exercise increases BDNF levels for quite some time.  Why?  Because BDNF is created by healthy vascular endothelial cells.  Cardiovascular health allows for BDNF creation.  How?  Shear stress--which is caused by blood flow over the lining of our blood vessels--activates the endothelium, and allows for BDNF secretion.
An active, moving body with an active, pumping heart is essential to the brain.
link

When will the tipping point occur?  When will MS specialists refer to the vascular connection to Multiple Sclerosis and begin to look at the endothelium?  When will they prescribe cardiovascular fitness to their patients?   When will they change the dialogue, to include heart health?

Still waiting for them---but you don't have to.
Move as much as you are able.  Incorporate an exercise program, and increase your own BDNF levels today.

Joan

 

Jugular Veins are Important

Recently published in the Journal of Mutiple Sclerosis, a review paper co-authored by Dr. Paolo Zamboni and Dr. Massimo Pedriali on the "Pathology of the Internal Jugular Vein in Multiple Sclerosis".   The complete paper is available on line for free---and I'd recommend it to all.  It is a very thorough review.

http://www.omicsgroup.org/journals/the-pathology-of-the-internal-jugular-vein-wall-in-multiple-sclerosis-2376-0389-1000160.php?aid=63610

As this review outlines, there are observable and documented differences between the jugular veins of healthy controls, when compared to people with Multiple Sclerosis.  These pathological differences involve the endothelial cells which comprise the veins' lining.  Endothelial cell aptosis (death) and derangement, as seen in MS, changes the ability of the jugular veins to drain.  Valvular and intraluminal abnormalities in the jugular veins of people with MS have hemodynamic implications.  There is a shift in collagen in the jugular veins of people with MS which affects venous compliance.

Veins have received little attention and research, when compared to the study and understanding of arteries.  Certainly, in terms of brain health, the carotid arteries are scanned and studied, and neurology and stroke researchers know that blockages, clots, and impairment in flow can be disastrous to the brain.  There are treatment modalities developed to deal with carotid artery issues---from medications to open surgery, to interventional proceedures.  No one questions the importance of healthy blood flow to the brain.

But the venous system and the removal of fluids from the brain is even more important than previously imagined.

During the past two years, international researchers have described a newly discovered lymphatic drainage system, which has actual draining vessels, and relies on the brain's draining veins.  These vessels take lymph fluid, carrying metabolites, proteins and toxins, out of the brain.  This process is aided by sleep.  This science is brand new.   It has reversed what we once believed was the brain's "immune privilege."
http://ccsviinms.blogspot.com/2015/06/rewrite-textbooks.html

This "stunning discovery" of a lymphatic drainage system relies on the jugular veins.

"Instead of asking, 'How do we study the immune response of the brain?' 'Why do multiple sclerosis patients have the immune attacks?' now we can approach this mechanistically. Because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels," said Jonathan Kipnis, PhD, professor in the UVA Department of Neuroscience and director of UVA's Center for Brain Immunology and Glia (BIG). 
http://ccsviinms.blogspot.com/2015/06/a-stunning-discovery.html

The brain is like every other organ in our body---it needs drainage.  Jugular veins are responsible for the exit of blood, cerebrospinal fluid (CSF) and lymph.  Any delays can cause changes to the brain's immune functioning, oxygenation, glucose metabolism and health.  Delays cause neuronal death and inflammation.  Or, what we see in multiple sclerosis.

Dr. Jonathan Kipnis, the discoverer of these lymphatic vessels, will be the keynote speaker at the International Society for Neurovascular Disease.  He will be presenting his research and proposals for studies in MS, alongside Dr. Zamboni and the other members of the ISNVD.

Here's the program.   “How the Extracranial Venous System Influences Neurological Diseases.”

http://isnvd.org/sites/default/files/ISNVD-2016%20meeting%20outline%20program%20guide%209-21-2015.pdf


This is not going away.
jugular veins are important,

Joan



Notice the difference between the top panel---healthy endothelial cells lining the jugular veins in normal controls, compared to the endothelial cells of a person with MS (bottom)

Figure 5: Scanning electronic microscopy. Top panel: regular disposition of the endothelial cells in IJVs of healthy controls, respectively at 800x (right) and 1500x (left). Bottom panel: irregular arrangement of the endothelial cells in the IJV of a MS patient, respectively at 800x (left) and 1500x (right). The cells appear lifted with craters.

Celebration!

UPDATE 2018---Jeff remains MS progression free eleven years after diagnosis, with no new lesions, and a continuation of healing.


Our family has some great news to share!  Jeff's new MRI shows a continued healing of his brain and spine.  His cervical lesions are now "less prominent" than they were on his last MRI in 2012, an indication of remyelination.   He has no new white matter lesions, and, most importantly, his gray matter structures are all healthy and normal, with no signs of atrophy.  This MRI shows actual healing---not placebo---when compared to Jeff's very first MRI in 2007, which showed gray matter atrophy and enhancing lesions on the spine and brain.

It has been 8 1/2 years since Jeff's MS diagnosis, and 6 years since his venoplasty treatment at Stanford.  Jeff remains physically and mentally active, and has stayed on the Endothelial Health Program.  He has had no MS progression.  We do not take Jeff's health for granted.  We are very thankful for the wonderful CCSVI community and researchers, and we consider this blessing of good health something which we are responsible to share. We want to stay involved in the neurovascular community at large, because we remain convinced that it is essential to look at the brain's blood, cerebrospinal fluid and lymphatic flow when evaluating treatments.  

MS is an inflammatory disease in which neurodegeneration and gray matter loss is the only correlate to disease progression.  The autoimmune hypothesis remains unproven.  All of the current drug treatments---now, a $20 billion a year industry--- are based on the EAE mouse model of MS, which relies on stopping immune activation in the central nervous system, and uses white matter lesions to measure "success" of a disease modifying med.  None of these meds have been shown to stop MS disease progression.

New research on the brain continues to come in, and points to the brain's reliance on the major draining veins to maintain gray matter structures.  MS specialists remain intransigent;  by refusing to consider how slowed venous flow and endothelial dysfunction might be affecting their patients' brain health.

Yet the evidence continues.  Outspoken advocates who have treated their own MS with cardiovascular means of diet, exercise and lifestyle changes continue to speak out and gain followers.  These individuals are pointing the way to health and healing for the MS brain.

Dr. Terry Wahls  http://terrywahls.com

Matt Embry  http://www.mshope.com

Dr. George Jelinek  http://www.overcomingmultiplesclerosis.org

Jeff Beal  http://ccsvi.org/index.php/helping-myself/endothelial-health


Even though each program has specific dietary differences (paleo, anti-allergen, low fat)---it's important to notice the lifestyle measures which these programs SHARE.

1. Healthy, whole foods, with plenty of colorful organic fruits and vegetables
2. Removal of processed foods and transfats
3. Smoking cessation
4. Increased intake of Vitamin D with UV ray exposure and supplementation
5. Regular cardiovascular exercise
6. Meditation or some form of stress relief
7. Consideration of the blood, CSF and lymphatic flow to and from the brain
8. Good quality and regular sleep
9. Maintaining a healthy weight
10. Addressing microbiome health with probiotics

There are things that can be done today, to help the brain heal.  Will these measures "cure" or "end" MS?  None of us know that for sure.  There may well be genetic factors which contribute to highly progressive MS, that cannot be completely addressed by these programs.  But we now have years and years of evidence compiling---Matt Embry is out the furthest with 20 years of no disease activity, George Jelinek is at 16 years, and Terry Wahls and Jeff are at eight years.

These numbers are impressive, and they matter.
Please be encouraged (which literally means, to give heart!!!)
The heart and brain are connected, and it's possible to take care of them.
You can do it, one day at a time,

Joan and Jeff

2015 ISNVD Conference Abstracts---research breakdown

The International Society for Neurovascular Disease (ISNVD) will be convening for the 5th Annual Conference in Naples, Italy at the end of March.  Abstracts for the presentations have been made available online here:
http://isnvd.org/d/sites/default/files/Invited%20Speaker%20abstracts%20-%20all.pdf

There are many more new presenters and international researchers attending this conference.  The ISNVD continues to grow in its membership and influence.

While neuroimmunologists stubbornly insist that there is no connection between diseases of neurodegeneration and circulation, this illustrious group of international researchers is showing that we are only at the beginning of understanding the impact of blood flow on brain health.

Here is my layperson's breakdown of the research abstracts and presentations.


2D and 3D analysis of vessels in the retina and the brain
Prof. Bart ter Haar Romeny, Ph.D.1,2
1Eindhoven University of Technology, Eindhoven, the Netherlands 2Northeastern University, Shenyang, China
This research is using the imaging of blood vessels in the eye's retina to get a picture of how blood is circulating throught the central nervous system. The blood vessels in the retina give an early picture of how brain diseases and breakdown of the blood brain barrier might be developing. Scanning the eye is easier and more cost-effective, as well.

Venous dysfunction and neurodegenerative diseases
Chih-Ping Chung MD PhD
Taipei Veterans General Hospital, National Yang Ming University, Taipei, Taiwan
Dr. Chung and his group have been studying the venous vasculature in relationship to brain disorders for over a decade. He has spoken at a few of the ISNVD conferences now. His new research focuses on how venous abnormalities are linked to white matter changes and how venous drainage impairment leads to dysfunction in Alzheimer's Disease.

Blood storage within the intracranial space and its impact on cerebrospinal fluid dynamics

Clive B Beggs 1, Simon J Shepherd 1, Pietro Cecconi 2 and Maria Marcella Lagana 2Medical Biophysics Laboratory, University of Bradford, Bradford, BD7 1DP, UK  Fondazione Don Carlo Gnocchi ONLUS, IRCCS S. Maria Nascente. Milan, Italy 
This study measured blood flow throughout the cardiac cycle by using MRI to visualize the flow in the necks of 14 healthy adults.  This study found that it is cerebrospinal fluid (CSF) which controls the volume changes inside the brain.  CSF interacts with the cortical veins to facilitate how much blood is stored.  This is an important finding, because any disturbance in venous outflow of blood and CSF will change the blood storage inside the skull, potentially leading to reduced cerebral circulation.

Advances in Treatment Strategies of Extracranial Venous Disease
Hector Ferral, MD
Senior Clinical Educator NorthShore University Health System
Dr. Ferral has been treating people with CCSVI for a few years now. He has also been an attendee and presenter at the ISNVD before. His new presentation will be looking at the technical advances being made in vein measurement and treatment of CCSVI.

Imaging of Brain Microvascular Disorders: lessons from the CADASIL model.

Hugues Chabriat, MD PhD;Department of Neurology, GH Lariboisiere, APHP, INSERM UMRS1161, University Paris 7 Denis Diderot, Paris France.
This research uses imaging to look at how the small vessel disease related to stroke and dementia develops and progresses.

Endothelin- 1 as a potential target for chronic brain hypoperfusion
Jacques De Keyser, MD, PhD, Free University of Brussels (VUB), Department of Neurology, Brussels, Belgium
This study is near and dear to my heart, as it is looking at how ET-1, a marker of endothelial dysfunction, is related to slowed blood flow in the brain, called hypoperfusion. People with MS have much higher levels of ET 1 in their blood than normals, and much slower cerebral blood flow. We also see this marker elevated in a number of neurodegenerative diseases, like Alzheimer's. In this study, the researchers used bosentan, a blood pressure medication, to treat ET 1 levels. This treatment increased cerebral blood flow in pwMS, and lowered ET-1 levels. (But bosentan has side effects, and is not easy on the liver. Much better, in my opinion, to lower ET-1 levels by addressing endothelial dysfunction, through diet, exercise, and lifestyle.)

TBI and hemodynamic changes in the brain
James R. Stone, MD, PhD
This presentation is looking at how traumatic brain injury induces ischemia, or a low-oxygen state, in the brain. TBI also changes cerebral blood flow and can cause a break in the blood brain barrier, igniting the immune system. New research is showing how explosive devices can cause TBI, even without direct physical contact.

Ultrasound contrast imaging of brain hemodynamic and perfusion Marcello Mancini, M.D.
Institute of Biostructure and Bioimage – CNR
Naples, Italy

This presentation will be looking at how new MRI and ultrasound technologies are allowing researchers to view cerebral circulation in MS.  People with MS show signs of hypoxia (low oxygen) injury and thrombosis (small clots) in the small veins of the brain. New technologies are allowing us to see that cerebral transit time is slowed in MS. 

Imaging of the Microvasculature
E. Mark Haacke, PhD 
Dr. Haacke, a presenter at all of the ISNVD conferences, returns this year to discuss how his invention of susceptibility weighted imaging (SWI) and MRA can be used to study the neurovascular system, and clarify the relationship between the venous sytem and CSF.


Update in computational fluid modelling of the brain
Mauro Ursino
This presentation is using mathmatical and computer models to simulate the complex mechanisms affecting cerbral circulation. Using these models shows how postural changes and stenosis in extra cranial arteries and veins can change upstream intercranial circulation.

Clinical Applications of Venous Treatment
Dr. Michael Dake, Stanford University

Dr. Dake, last year's ISNVD president and a founding member, will be presenting on the contributions of 2014 studies which have enhanced understanding of how endovascular and open surgical treatment of venous abnormalities has affected patients with MS, Alzheimer's disease, Parkinson's, POTS and other pathologies.

The Heart Brain Connection
MJ Daemen
Dr. Daemen is the keynote guest speaker. He is a neurocardiologist, a member of a new field of experts who are bringing together an understanding of how the heart and brain affect each other. As a member of the Dutch Heart Foundation, his group is looking at how cardiovascular disease is influencing cognitive function and cerebral circulation.

A NOVEL SONOGRAPHIC METHOD FOR REPRODUCIBLE JUGULAR VEIN PULSE WAVE ASSESSMENT
Paolo Zamboni, Francesco Sisini, Erica Menegatti, Giacomo Gadda, Mirko Tessari, Mauro Gambaccini
Vascular Diseases Center, University of Ferrara, Ferrara, Italy 

Dr. Zamboni's group is using ultrasound in the B mode (brightness mode) to measure the pulse wave in the jugular vein.  The way that the wave form looks is currently used to monitor for heart disease, however Dr. Zamboni's group is using this technique to find CCSVI.

Is there a role for mast cells dependent synthesis of Endothelin-1 in neurodegenerative diseases?
Pedro D’Orléans-Juste-1, Louisane Desbiens, Denis Gris-2
Departments of Pharmacoly-1 and of Pediatrics-2, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, PQ, Canada

We know that levels of ET-1 (a marker of endothelial dysfunction) and mast cells (tissue cells of the immune system) occur in higher levels in people with MS.  This study uses the mouse model of EAE as well as a human isoform to study how mast cells found in the vicinity of spinal lesions are involved in the synthesis of ET-1.

Venous abnormalities in Meniere's Disease

P.M.Bavera; P. Cecconi; D. Alpini; F. Di Berardino 

This presentation will be using slides to show the correlation and differences between Meniere's Disease and MS, in regards to CCSVI imaging.  There are specific characteristics to the venous abnormalities seen in Meniere's.

Advances in Idiopathic Intracranial Hypertension Pathogensis: a Focus on Sinus Venous Stenosis
Roberto De Simone, Angelo Ranieri
Headache Centre  Dpt. of Neurosciences, Reproductive Sciences and Odontostomatology University of Naples “Federico II”

This research is focusing on how stenosis of the venous sinus is related to idiopathic intracranial hypertension (IIH)  There is a feedback loop which appears to occur in this situation.  The venous sinus collapses, cerebrospinal fluid pressure builds, which creates more compression.  Endovascular stenting of the venous sinus is a currently approved treatment to end this cycle of stenosis and hypertension.

In Endothelial function, the glymphatic system and New Drug Development
Endothelial dysfunction in neurodegenerative disease
J. Winny Yun, Emily Stevenson, Seiichi Omura, Fumitaka Sato, Ikuo Tsunoda, Alireza Minagar, Felix Becker, Trevor Castor, Adam Xiao, J. Steven Alexander, LSUHSC-Shreveport Molecular and Cellular Physiology, Microbiology, Virology, Neurology, Shreveport, Louisiana, USA.
Dr. Steven Alexander from LSU returns to the ISNVD to again discuss the endothelium in neurovascular disease. There is a vascular association of specific biomarkers found in MS. This new research is looking for a means to regulate these neurolymphatic markers, to help those with neurovascular diseases.

Fluid Dynamic Influences on Cerebrovascular Endothelial Activation Responses
Dr. Alexander and the LSU team look at how blood flow over endothelial cells affect their health. Laminar shear stress (regular blood flow) over endothelial cells is essential to their function. Disrupted flow causes endothelial cells dysfunction and death. Shear stress alterations could lead to a break down of the endothelial layer in the brain, and create a disturbance in the blood brain barrier and inflammation.

Cardiovascular risk factors and neurodegenerative disorders
Dr. Robert Zivadinov
Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, State

This research finds an association with cardiovascular risk factors (smoking, obesity, inactivity, high blood pressure) and MS.  MS patients who had one or more CV risk factors had higher lesions loads and more brain atrophy.

Avanti!

Joan

New research on the Heart-Brain Connection in MS

More and more researchers are looking at the connection between heart health and brain health in Multiple Sclerosis.  It was seven years ago I first contacted cardiovascular and endothelial specialist Dr. John Cooke at Stanford University regarding my theory that serum markers of endothelial dysfunction might be pointing to a connection between the heart and brain in MS.

Dr. Cooke was very kind in responding to me, and said that the research I had compiled appeared to point to an association, but that the MS specialists he talked to at his university asserted the autoimmune nature of the disease, and the lack of connection between the heart and brain health in MS.  At that time, not many researchers considered endothelial dysfunction a component on MS disease progression.  Endothelial dysfunction was a known contributor to heart disease and stroke, however researchers weren't really looking at it in terms of diseases of neurodegeneration.

In fact, when I wrote about the endothelium, most lay people and even some medical people I spoke to had never encountered the word, but thankfully, this is changing. The endothelium is the largest secreting organ in the human body.  It is the layer of cells which line the 60,000 miles of blood vessels that nourish our bodies.  When endothelial cells are damaged and die, we see markers of this in the blood.  Endothelial health is essential to the health of the body's organs and tissues.  The heart and brain included.

Today, more and more MS researchers are considering this connection.

There is about 30% higher risk of the myocardial infarction in patients diagnosed with multiple sclerosis (MS) than in people without MS. Increased risk of cardiovascular disease development positively correlates with levels of serum markers of an endothelial dysfunction, and may give rise to a global cerebral hypoperfusion. It appears that these complications precede progressive loss of axons, which mechanisms are complex and should be linked to a loss of β2 adrenergic receptors on astrocytes of demyelinating lesions. Consequence of this deficiency, the cause of which is not known yet, is a decline in energy metabolism of axons. Moreover, the loss of these receptors is linked to a reduced redistribution of potassium ions by astrocytes, glutamate excitotoxicity and increase of calcium ion concentration in the axon with subsequent activation of necrotic processes. In addition to immunological aspects we should take into account also parameters of the functional state of endothelium when appropriate targeted therapy for patient is considered. http://www.ncbi.nlm.nih.gov/pubmed/25702293

Serum markers of endothelial dysfunction which can be regularly tested are levels of c reactive protein (CrP), hypercoagulation (SED rate, ESR), and fibrinogen or thrombin (d dimer).  In fact, researchers already know that all of these blood markers are found to be high in people with MS.  When Jeff was diagnosed in 2007, his serum numbers for these markers were sky high.  Which is why I started this line of inquiry in the first place.
http://ccsviinms.blogspot.com/2014/03/blood-matters.html 

Another new study has found that people with MS who also had one or more cardiovascular (CV) risk factor (obesity, smoking, inactivity, hypertension) had higher lesion load and more pronounced brain atrophy.

Patients with MS showed increased frequency of smoking (51.7% vs 36.5%, p=0.001) and hypertension (33.9% vs 24.7%, p=0.035) compared with HCs. In total, 49.9% of patients with MS and 36% of HCs showed ≥2 CV risks (p=0.003), while the frequency of ≥3 CV risks was 18.8% in the MS group and 8.6% in the HCs group (p=0.002). In patients with MS, hypertension and heart disease were associated with decreased grey matter (GM) and cortical volumes (p<0.05), while overweight/obesity was associated with increased T1-LV (p<0.39) and smoking with decreased whole brain volume (p=0.049). Increased lateral ventricle volume was associated with heart disease (p=0.029) in CIS.
Patients with MS with one or more CV risks showed increased lesion burden and more advanced brain atrophy.

http://www.ncbi.nlm.nih.gov/pubmed/25722366

What does this all mean?  Living a cardiovascularly healthy lifestyle benefits more than the heart.  It can keep the MS brain from atrophying and delay progression.

These are all things that can be done today with nutrition, exercise and lifestyle which will maintain brain health.

Here's the program I created for Jeff, based on the connections I saw all those years ago.  He's still on the program, and it's still helping him keep his serum numbers in the normal zone, with no MS progression.
http://ccsvi.org/index.php/helping-myself/endothelial-health

I hope this might encourage you to learn more about the connection between your heart and brain, and your amazing endothelium!

Joan

From cells to space stations--vascular research continues

While astronaut Samantha Cristoforetti works high above our planet on the International Space Station---studying venous return in microgravity and utilizing Dr. Paolo Zamboni's technologies----cellular biologists are looking at the MS brain. The macrocosm and the microcosm of MS vascular research is happening right now!

New technologies are allowing researchers to view the MS brain at a cellular level, before formation of lesions.  I wanted to share three of these new papers, all published in the last month.

Please note that the researchers are cellular biologists---they are looking at the MS brain on the most basic level, and they all see the vascular links to the disease.  They are not studying MS to find out how immune modulating drugs work, they are trying to solve the mystery of what causes MS.  And they are all seeing a connection to blood flow and the blood brain barrier.

When neurologists tell you CCSVI research is over, please point them to the continuing, confirming research which is further elucidating the vascular connection to MS. 

If NASA can work directly with Dr. Paolo Zamboni, why won't neurologists?
NASA wants to understand why 20% of their astronauts are coming back to earth with neurological and visual issues, and how it's related to blood flow.  So, they went to the expert.
http://www.nasa.gov/mission_pages/station/research/experiments/1278.html

Here are the brand new papers, all finding a link to MS and blood flow.

1.  The Role of Angiogenesis in the Pathology of MS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4253611/

Cell biologists from the University of Irvine have noted how the loss of endothelial tight junctions in the blood brain barrier contributes to inflammation and angiogenesis (the growth of new blood vessels) in the MS brain,  and how this process is initiated by hypoxia.  This low oxygen state and resultant angiogenesis occurs prior to formation of demyelinating lesions.

This cellular research is further defining the hypothesis of cellular biologist Dr. Bernhard Juurlink, made in the 1990s.
http://ccsviinms.blogspot.com/2010/08/blood-flow-and-white-matter-lesions.html

It also fits in with my hypothesis of MS as a disease of hypoperfusion/reperfusion injury.
 http://ccsviinms.blogspot.com/2013/09/multiple-sclerosis-hypoperfusionreperfu.html


2. In vitro study of the direct effect of extracellular hemoglobin on myelin components.
http://www.ncbi.nlm.nih.gov/pubmed/25463632

The cellular biologists from the University of Guelph are looking at how blood particles damage myelin.  They are seeing microscopic deposits of hemoglobin in the MS brain, around the veins.  This blood contains iron, which when deposited into delicate brain tissue, begins a process of oxidative stress.

"This study provides new insight into the mechanism by which hemoglobin exerts its pathological oxidative activity towards myelin components. This work supports further research into the vascular pathology in MS, to gain insight into the origin and role of iron deposits in disease pathogenesis, or in stimulation of different comorbidities such as cardiovascular disease."

This work confirms the theory of Dr. Zamboni from 2006, called his "Big Idea" theory, which saw the similarities of venous disease to MS, by noting how blood particles caused damage to tissue via the iron found in our red blood cells.   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1633548/

3.  Focal disturbances in the blood brain barrier are associated with formation of neuroinflammatory lesions

http://www.ncbi.nlm.nih.gov/pubmed/25448765

Neurobiologists from the University of Montreal are seeing changes to the blood brain barrier which happen before immune cells enter the MS brain. There are changes to the tight junctions of endothelial cells. 

 Our findings suggest that BBB breach occurs before significant immune cell infiltration and demyelination.

I wanted to briefly highlight these new studies, and encourage all readers to pursue cardiovascular and endothelial health in 2015.  

The discoveries of endothelial dysfunction and the link to the breakdown of the blood brain barrier in MS are being made.  While we wait for the venoplasty and pharmaceutical solutions, there is much that can be accomplished with lifestyle changes.
http://ccsvi.org/index.php/helping-myself/endothelial-health

Happiest of holidays to all.  Here's to a healthy 2015.

Joan

Here is Samantha's view                                               Here is a microbiologist's view

You and Your Microbiome

During the past year, there has been a lot in the medical press on the "microbiome."   Researchers continue to explore the connection between the microbiome and neurodegenerative disease.  Articles on the microbiome and MS, Alzheimer's, and dementia as well as cardiovascular disease and stroke, are being published in medical journals and discussed in online communities.

You might say 2014 has been the Year of the Microbiome!

But what is it??  Microbiome literally means the "small living community" inside each of us.  It's the word doctors and researchers use to describe your own, unique ecosystem.  You see, we are not just "ourselves", we are also host to a universe of living organisms.  And most of these guests take up residence in our gut.

We have about two pounds of bacteria living inside us.  These bacteria are broken down into four families: the Actinobactera, Bacteroidetes, Firmicutes and Proteobacteria.  http://www.nature.com/nri/journal/v13/n11/fig_tab/nri3535_F2.html

When these families live in balance, the human body functions better.  When these families get knocked out of balance, diseases can be linked.  "Dysbiosis" is when inflammatory bacteria outnumber beneficial bacteria.  Whether the link to specific diseases is causal, or resultant, is yet to be established.  But there's more and more evidence connecting an imbalanced microbiome to inflammation and diseases of "autoimmunity."

Here are some more specifics on what researchers found, when looking at the fecal bacteria in people with MS, and comparing them to healthy controls.  This is Dr. Sushrit Jangi of Brigham and Women's Hospital discussing results of a recent study:

The preliminary data show that there are at least a couple of different genera of bacteria that are different in the gut of MS patients compared with healthy controls. We found that a bug called Methanobrevibacteriaceae *** is enriched in the gut of MS patients and seems to have immunoproliferative properties that drive inflammation. We also found that the population of Butyricimonas ### bacteria is low in MS patients compared with healthy controls. This is an interesting result because these bacteria produce butyrate, which is thought to be immunosuppressive, but we do need to repeat this study in a larger cohort.

So it seems that our work initially supports the idea that the gut in MS patients contains bugs that drive inflammation and are low in the types of bacteria that control inflammation. This is consistent with work in rheumatoid arthritis and inflammatory bowel disease.

This also mirrors the idea that MS is a disease of the western world. If you go to countries like India and parts of Asia, where diets are far more vegetarian, you don't really see MS. However, when these people come to the United States and adopt a more westernized diet, the incidence of the disease goes up. I think this is an exciting premise but it's still too early to say anything about the causality.
http://www.medscape.com/viewarticle/832385

***Methanobrevi bacteria are found to be enriched in those who are constipated.  
https://microbewiki.kenyon.edu/index.php/Methanobrevibacter_Smithii
### Batyricimonas is also low in RA and inflammatory bowel disease.
http://journals.lww.com/neurotodayonline/blog/breakingnews/pages/post.aspx?PostID=316

I included probiotics and eating more plants in the Endothelial Health Program, because I read a lot of research on the link between bacteria, inflammation and the endothelium.  And I wanted to help Jeff.  He was severely constipated when we started the program (sorry, hon!  Is that TMI?)  His serum numbers were off the charts for inflammation.  His meat and animal protein to plant food ratio was far too high in meats, too low in vegetables and fruits.  His just wasn't eating enough living, plant-based foods with phytonutrients and fiber.  I thought there might be a connection, and found it in the endothelium.  Here is a post from 2011, where I explain:

http://ccsviinms.blogspot.com/2011/07/probiotics-and-brain-gut-link-july-7.html

Probiotics, also know as helpful bacteria, are included in the Endothelial Health program, because they affect the lining of our blood vessels in a positive way, by reducing inflammation and regulating NO. A strong endothelium is less permeable, and will keep plasmic particles out of tissue--in the brain and the gut.  This can modify the reaction of immune cells, and reduce what is called the "autoimmune" reaction.  (Although I believe calling this reaction "autoimmune" is a misnomer.  The immune cells are simply doing their job, by responding to foreign particles which should not be in brain or intestinal wall tissue.)

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

What to do?  How can we create a more balanced, happier microbiome, and encourage growth of healthy bacteria?   There are a few things scientifically proven that we can do today, while the researchers continue to look for specific answers.

1. Work with your own healthcare provider, and find a probiotic solution that fits your lifestyle and needs.  Some people eat yogurt, others prefer fermented foods like sauerkraut, kimchi or kombucha, or some take a probiotic supplement.  Some folks (like me!) enjoy all three.  Jeff finds his supplement is enough.   Each individual needs to discover what works best for them.

2. Eat more plants, eat less meat and animal products.   And stay away from processed foods. The research shows that the more saturated and trans fats, the less balanced the microbiome.  The more fresh vegetable and fruits, the better the microbiome.

3. Watch your bowel movements!  Are you going at least once a day?  If not, you're not moving waste products through your body efficiently, and that build up of noxious or "bad" bacteria may be enhancing inflammation in your body.  If you are having a couple smooth, not runny, bowel movements a day, chances are, your microbiome is pretty happy.  (sorry, was that TMI again??)

4. Stay at a healthy weight.  Obesity is linked to an unbalanced microbiome.


Let's be good hosts to the universe within us all!
Joan

Genetics and MS

Every few months, there is a news story lauding the fact that researchers have finally verified that MS is autoimmune.  These stories have a similar theme.  MS is most certainly autoimmune, because the connections made between MS and genes are all found in the immune system.  

But that's because it is the only place researchers are looking.  The major histocompatilbility complex (MHC) region remains the area under exploration, now 40 years since its initial discovery.

And they continue to get research grants from pharmaceutical companies to continue to look at the same location, because making this connection to the autoimmune theory advances drug sales.

In fact, the connection to heretability and genetics in MS is rather slim.  In identical twins, genetic risk is less than 1/3 if one twin has MS.  

...there is a 2% to 4% elevated genetic risk in siblings of patients with MS and a 30% greater risk in identical twins.
http://www.medscape.com/viewarticle/833070



There was a recent story in the NY Times regarding research into a potential genetic link found in those who die due to Ebola infections.  Researchers Angela L. Rasmussen and Michael G. Katze of the University of Washington  found a problem with blood vessels, which were allowing immune cells open access and an overblown reaction to the virus. That's right.  Death from Ebola happens because of a break down of the endothelium, or the lining of blood vessels.  And there is a potential genetic link.
http://www.nytimes.com/2014/10/31/health/genes-influence-ebola-infections-in-mice-study-suggests.html?_r=1

About two-thirds of people who die from Ebola never develop the terrifying hemorrhages that appear in others a day or two before death, in which eyes turn fiery red, gums bleed, red dots emerge on the skin as blood seeps out of capillaries, and blood appears in vomit and diarrhea. Many mice, too, die of Ebola without hemorrhages.

The mouse studies indicate the animals that hemorrhage and — by implication, humans— die because their immune systems overreact to the virus. The result is an inflammatory response that makes cells leak fluids and white blood cells, and makes tissues and organs deteriorate. Many die at that point. In those mice — or humans — that survive long enough, the researchers propose, blood eventually starts to seep out of vessels.

In fact, researchers found a genetic link to two specific genes, which were allowing for the overblown inflammatory response.

The mouse studies showed that animals that died after bleeding had an overblown inflammatory response to the virus. They also had low activity of two genes, Tie1 and Tek, that made their blood vessels more permeable. The leaky vessels allowed white blood cells to stream out, escalating the inflammatory response and causing a chain reaction of damaging immune system chemicals that destroyed organs. 

She said that “a big take-home lesson from the paper” is that genetics plays a major role in determining the outcome of a mouse’s Ebola infection. By inference, she said, genetics probably plays the same role in humans.

(for those who enjoy learning more, here is a paper on how Tie1 and Tie2 (TEK) are involved in vascular permeability.)
http://www.bloodjournal.org/content/93/6/1969?sso-checked=true

An overblown inflammatory response due to a breakdown of the lining of the blood vessels.  Sounds like something MS researchers might want to investigate, especially considering the recent research of Dr. Yulin Ge of NYU.

At the ISNVD conference in February 2014, Dr. Yulin Ge discussed how 7T MRI technology is allowing us to see tiny hemorrhages in the MS brain which occur before demyelination.  This further elucidates the microvascular connection to MS.
From his abstract at the ISNVD:

Being the most common demyelinating disease of the central nervous system, multiple sclerosis (MS) MS has a significant microvascular pathological component as a consequence of the perivascular inflammation. The role of vascular pathology in MS was suggested long ago. Now there is accumulating evidence of a primary vascular pathogenesis in MS. In vivo studies of vascular and hemodynamic impairment in MS may provide insights into the etiology and pathophysiology of MS and offer the potential metrics for assessment of outcome of the disease. 

http://ccsviinms.blogspot.com/2014/03/blood-matters.html

The definition of insanity is repeating the same act over and over and expecting different results.  Continually searching in the same place for a genetic link to MS is not bringing us any closer to understanding MS aetiology.  It's making money for research labs and drug companies, but it is not bringing health and healing to people with MS.

Thanks to the ISNVD, for looking beyond the autoimmune paradigm.

Joan

Understanding Endothelial Dysfunction--learning from Ebola crisis

The horrific outbreak of the Ebola virus in West Africa is causing researchers and physicians around the globe to ask what can be done to slow the death rates in this vulnerable population.

A recent piece in the New York Times, titled "Can Statins Help Treat Ebola?"  is authored by Dr. David S. Fedson, a retired professor of medicine at the University of Virginia.  Dr. Fedson writes about the current crisis of the Ebola epidemic and the short supply of life-saving drugs.  He suggests that there are other treatments, aside from experimental and expensive drugs, that have already been tested in humans, are readily available and can modify the body's response to the virus.

How would these drugs help?  They target endothelial dysfunction.

More than a decade ago, clinicians noted striking similarities between patients with Ebola and those with bacterial sepsis. Both diseases involve severe dysfunction of the endothelial cells that line blood vessels throughout the body. This dysfunction in turn precipitates major abnormalities in blood coagulation. Both can eventually lead to the failure of internal organs, primarily the liver and kidneys, and organ failure often leads to death. 

Researchers have since discovered that abnormalities of endothelial function and coagulation can be modified or reversed by treatment with drugs such as statins, angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs), which were developed to treat patients with cardiovascular diseases and diabetes. 
http://www.nytimes.com/2014/08/16/opinion/can-statins-help-treat-ebola.html?_r=1

Dr. Fedson suggests that strengthening the endothelium with cardiovascular drugs may be the key to stopping organ failure and saving lives in the Ebola outbreak.

These very same statins have been suggested as a treatment for secondary progressive multiple sclerosis, as they reduced brain atrophy (from 0.6% to 0.3% per year) in pwMS when compared to placebo.  MS doctors are more accepting of a pill, rather than life-style modification, when treating disease, as a pill can be placebo-controlled and trialled.  And they most certainly never explain why cardiovascular treatments might slow brain atrophy.  But as we have all learned, it's because of blood flow to the brain.
http://www.sciencedaily.com/releases/2014/03/140318190031.htm

In fact, all of the above mentioned cardiovascular drug treatments are now being tested in people with MS, to slow down neurodegeneration and brain atrophy; death of brain tissue due to endothelial dysfunction.  These drugs are not immune modulating---rather, they address blood flow, endothelial function and coagulation.  Here's more on the new medications being tested in MS.
http://ccsviinms.blogspot.com/2013/08/medications-for-ms-addressing-blood.html

What can those with a chronic and progressive disease like MS take away from this deadly Ebola outbreak?   There is a vascular connection to this terrible disease, as there is a vascular connection to MS.  A strong endothelium is the body's best defense.  Keeping the blood vessel lining healthy and impermeable is the surest way to maintain cerebral circulation for those with MS.   Endothelial health will slow brain atrophy and may even reverse it.

But you don't need a statin.  There is much that can be done with lifestyle, nutrition, and exercise.
http://ccsvi.org/index.php/helping-myself/endothelial-health

Here's to more healing ahead!
Joan

The Endothelium

Update  APRIL 2019
More research continues to come in, linking endothelial dysfunction to multiple sclerosis.  Pub med has hundreds of new papers. 
https://www.ncbi.nlm.nih.gov/pubmed/?term=multiple+sclerosis+endothelial+dysfunction

++++++++++++++++++++++++++++++++++++++++++++

When I first began looking into how Jeff's MS was related to his vascular system in 2007,  I read many papers on pubmed which discussed the "endothelium."  A dysfunction in the lining of our blood vessels was implicated in chronic diseases of inflammation and hypoperfusion, such as MS.  I noticed that there were many modern day environmental factors that caused problems with endothelial health and blood flow.  Endothelial dysfunction was linked to diabetes, cardiovascular disease, autoimmune disease and neurodegenerative disease.  

Fast-forward seven years, and there are health stories on the endothelium in the mainstream press every day.  Here's a sampling from just last week----

Tomato Sauce helps fight heart disease   Of 36 patients with heart disease, those taking the pill every day for two months saw their blood vessels widen by 53 per cent.  This was due to improved functioning of the endothelium, the inner wall cell lining of blood vessels, scientists believe. link

How the brain regulates blood flow   Hillman found that the vascular endothelium, the inner layer of blood vessels, plays a critical role in propagating and shaping the blood flow response to local neuronal activity. While the vascular endothelium is known to do this in other areas of the body, until now the brain was thought to use a different, more specialized mechanism and researchers in the field were focused on the cells surrounding the vessels in the brain.link

Eating Strawberries may lower blood pressure   Strawberries are rich in antioxidants, which may lower blood pressure by relaxing the endothelium, the lining inside blood vessels.  Relaxing the endothelium widens the arteries, reducing pressure.link

So, now that we know the endothelium is truly important---how is our current environment impacting our health?   And what can we do about it?
Here's what I wrote in 2007:

                                                            

I truly believe endothelial dysfunction is the disease of modern man, and is responsible for the increasing rates of chronic disease in industrialized nations.

To provide a contrast and by means of example, I present a day in the life of two women, separated by only 200 years in time.

19th Century- Life as it been lived for thousands of years-

You and your husband get up from bed as the sun rises and the rooster crows. You both get dressed and head outside together to milk the cows and feed the livestock. You work the pump at the well, get a drink of water, which comes from a fresh spring underground. The physical exertion of pumping water and carrying it, lifting the feed and milking the cows has worked up a good sweat. You gather some fresh eggs from the henhouse, and head inside to cook breakfast. The meal includes coffee or tea made with spring water, fresh milk from the cow, eggs and toast with apple preserves, jarred last fall.

The children rise, get dressed, eat and are soon out the door to walk to school. Your husband heads off to his work in the barn. There is laundry to be washed and hung on the line and gardening to do. You spend over two hours out doors, in the sunshine.  Again, hard work and more exercise. This is not a life of leisure!

Fresh fruits and vegetables are eaten in season and canned and jarred for off season.  There isnʼt much meat, but an occasional fish from the stream or chicken from the henhouse. Grains are whole, and you add flaxseed to the bread. Root vegetables and greens are plentiful. Mealtime is spent together as a family. After dinner, and after the dishes pots and pans are cleaned, the family sits together and reads or plays board games. Soon the sun sets and itʼs time for bed. Everyone is tired from the dayʼs activities and ready to sleep.

21st Century--Our Modern Life

You rise in the dark to the incessant buzz of the alarm clock. Itʼs a quick shower in chlorinated and fluoridated city water and blow dry before heading to the kitchen to make a pot of coffee. You get your water from the tap and microwave a breakfast sandwich of processed ham and cheese to go. You check your e-mail on the laptop and holler to wake your husband and the kids and hurry them up- thereʼs no time to waste! They get dressed, grab their backpacks and eat their microwaved breakfasts as everyone piles into the van.

Itʼs off to school where you drop them at the door. Then you get back on the freeway to sit in traffic. Love those fumes! Youʼre starting to get a headache. Trapped on the road, you try to make good use the time by calling clients and checking your phone. Your stress levels are now through the roof of the van. You get to the office late and have to deal with everything that has been piled on your desk. No time for the gym, and lunch is going to be a bag of peanut M&Ms and a can of Coke. You never see the light of day, except through your office windows. By the time you get home, itʼs dark and the kids are fighting over the Playstation.

You still need to make dinner. Your husband has texted you, heʼs running late and will miss dinner...again.

You pile the kids back in the van and head to a fast food place. Itʼs drive through and the kids donʼt mind. Youʼre famished and get a double cheeseburger, since you skipped lunch, how could it hurt? You get everyone home and get the kids doing their homework. Itʼs nine pm before you know it, and your husband finally gets home. He walks in and just wants to sit in front of the TV, heʼs exhausted. You get the kids bathed and into bed. Itʼs 11pm before you fall into bed, head pounding. You have trouble sleeping, and it seems like by the time you finally drift off, the damn alarm is ringing again!

I do not mean to over-romaticize or idealize the lives of men and women from centuries ago. Theirs was a very different experience, and it was physically and emotional demanding. People got sick then, very sick, and many died premature deaths. But not many suffered from chronic diseases. Our modern lifestyle is much easier in many ways-- we have automated appliances to do our labor, vehicles to transport us, and conveniences our great, great grandparents could only have dreamed of. 

Our modern lifestyle has disrupted many natural and hormonal patterns; such as the circadian rhythm. We no longer use the sun to tell us when to rise and set. And doctors are seeing a deficiency of vitamin D (the sunshine vitamin made by our skin when exposed to sunlight) linked to many diseases. Not coincidentally, lack of vitamin D is one of the causes of endothelial dysfunction.

                                                                        +++++++++++

More science continues to come in, and we've learned how endothelial dysfunction is linked to slowed cerebral blood flow and inflammation. Some of the modern lifestyle/environmental factors which have been linked to endothelial dysfunction are:

1. Lack of UV rays, low nitric oxide and low Vitamin D

2. Lack of exercise and sedentary living

3. Higher stress and cortisol release

4. Lack of REM sleep and regular circadian rhythms

5. Too much glucose and refined sugar

6. Eating transfats and processed foods

7. Toxins, pesticides and heavy metals in air and food

8. Lower intake of whole foods, fruits and vegetables

And not coincidentally, when countries become industrialized or "westernized", rates of chronic diseases rise. 

Nevertheless it was the Industrial Revolution (with the widespread use of refined vegetable oils, refined cereal grains, and refined sugars)14,65 and the Modern Age (with the advent of the “junk food” industry, generalized physical inactivity, introduction of various pollutants, avoidance of sun exposure, and reduction in sleep time and quality coupled with increased chronic psychological stress)14,38,65,146,152,153,160 that brought about the most disruptive and maladaptive changes, which may have serious pathophysiological consequences.  link

Take care of your endothelium and it will take care of you.

For more information:

http://ccsvi.org/index.php/helping-myself/endothelial-health

Joan