Welcome! This blog contains research & information on lifestyle, nutrition and health for those with MS, as well as continuing information on the understanding of CCSVI and cerebral hypoperfusion. This blog is informative only--all medical decisions should be discussed with your own physicians.

The posts are searchable---simply type in your topic of interest in the search box at the top left.

Almost all of MS research is initiated and funded by pharmaceutical companies. This maintains the EAE mouse model and the immune paradigm of MS, and continues the 20 billion dollar a year MS treatment industry. But as we learn more about slowed blood flow, gray matter atrophy, and environmental links to MS progression and disability--all things the current drugs do not address--we're discovering more about how to help those with MS.

To learn how this journey began, read my first post from August, 2009. Be well! Joan

Wednesday, May 17, 2017

MS is vascular


MS is caused by a breakdown of cerebral endothelial cells.  The loss of these vascular cells, which line all 60,000 miles of our blood and lymph vessels, is why the blood brain barrier becomes open, how immune cells are called in creating inflammation, why the coagulation cascade occurs increasing fibrinogen, what allows for death of neurons,  what causes MS to progress.

For those who hate medical language, find it confusing, and like easy to understand explanations, I wrote up a simple post on the endothelium and how it works here:  link

I'm not the only one saying the endothelium is central to MS.

A new paper, edited by MS neurologist Lawrence Steinman at Stanford University states the following:

Endothelial cells (ECs) in the CNS form a unique blood–brain barrier (BBB) that is broken down in multiple sclerosis (MS). New therapies are sorely needed to restore BBB function in this disease.

Disruption of the blood–brain barrier (BBB) is a defining and early feature of multiple sclerosis (MS) that directly damages the central nervous system (CNS), promotes immune cell infiltration, and influences clinical outcomes. There is an urgent need for new therapies to protect and restore BBB function, either by strengthening endothelial tight junctions or suppressing endothelial vesicular transcytosis.

This paper is a collaborative review from Columbia University, UC Irvine, Stanford and the Albert Einstein College of Medicine.  You can read the abstract here:
link

I really don't know how else to say it.  Your endothelium is important.  I've been blogging about this scientific reality since my first post on this blog.  Hundreds of my posts are about endothelial cells, why they are important, why they die, how to maintain them.  Obviously, I didn't do the research, I just put it together.  

Yes, I am gratified that universities acknowledge the importance of the endothelium in MS.  But so much of this remains a continued search for industry funding and "pharmacologic enhancement" rather than a search for the etiology, or cause of MS.  Or an understanding of how the endothelium is damaged by a variety of lifestyle, vascular and disease factors.  

I wanted to understand how to protect and strenghten the endothelium, which is why I originally contacted Dr. John Cooke, a researcher at Stanford University who had published a book on nitric oxide and lifestyle measures to heal the endothelium in cardiovascular disease.  He is now at Houston Methodist, heading up a lab which is creating endothelial cells from stem cells, for use in regenerative medicine.  He's getting there!  link

Below are the interventions we discussed, which I compiled for Jeff and others with MS.  The endothelium can heal by using these strategies.   Jeff has done really, really well following this program.  I have also heard from other people with MS who are employing these measures, and finding health and stability.  Please talk to your own doctors before beginning any lifestyle program, to make sure it is right for you.  I am not a doctor.  But I trust people like Dr. Cooke.
http://ccsvi.org/index.php/helping-myself/endothelial-health

The International Society for Neurovascular Disease recently had their 7th annual conference.  This year, the President of the ISNVD was Dr. Stephen Alexander.  I originally met Dr. Alexander online and later in person at the first meeting of the group which would become the ISNVD, back in 2009 in Bologna, Italy.   Dr. Alexander is an endothelial researcher who studies endothelial cells in MS and inflammation.  He and his fellow researcher, Dr.  Alireza Minagar, have published many papers on the vascular connection to MS.

This is their paper, which caught my attention ten years ago:
Multiple Sclerosis as a Vascular Disease


Their most recent effort is a chapter included in the book "Inflammatory Disorders of the Nervous System" called "Emerging Roles of Endothelial Cells in Multiple Sclerosis Pathophysiology and Therapy"

The complex pathogenesis of MS can only be appreciated when and if vascular contributions are recognized as a significant part of MS etiology. Indeed, many novel therapies for MS target the mechanistically relevant vascular inflammatory features of these conditions and implicate cerebrovascular endothelial cells (CECs) as the “failing gatekeeper” of the blood-brain barrier (BBB).    link


And yes, CCSVI is a factor.  When blood flow is disturbed, due to venous hypertension or stenotic blood vessels,  there is a lack of shear stress over endothelial cells, and they die.  Endothelial cells need constant moving blood.  Here is a paper from Dr. Alexander on Venous Endothelial Injury in Diseases of the CNS.   https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-219

While researchers continue to put together the pieces and find pharmacological means to strengthen the endothelium, there are things you can do today to help yourself.

I know, I repeat myself.  A lot.  Because this is important.

Heal the endothelium, heal the vasculature, heal the body.

Joan





The brain’s blood vessels are lined with endothelial cells that are wedged tightly together, creating a nearly impermeable boundary between the brain and bloodstream.














Friday, April 28, 2017

The Endoplasmic Reticulum (ER), Rab32 and MS

Once again, the medical news headlines are full of "breakthrough!" "cause of MS!" "new way of looking at the disease!" and even "Cure!"
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Researchers in the UK and Canada have found the protein Rab32 appears in large quantities in autopsied brain tissue of those who had MS.  Higher levels of this protein cause a disruption of communication between cells, and lead to mitochondrial malfunction and neurodegeneration.  Researchers say they do not know what causes this increase in Rab32, but they believe that by inhibiting this protein with new treatments,  they can slow MS progression.  However, neurovascular researchers have been studying this mechanism for many years in Alzheimer's, ALS, Parkinson's and dementia---and vascular researchers know why this happens (keep reading.)
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I find it's always a good idea to read the actual research, rather than rely on click bait or fake news headlines.  Many medical reporters have only a basic understanding of science.  The researchers who send out press releases like to keep it that way. The news stories continue to mention the autoimmune theory of MS right at the start, yet this new discovery has little to do with autoimmune disease, and almost everything to do with inflammation of the vasculature and endothelial dysfunction.

Here is the complete paper:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260063/

Together, using multiple patient tissue samples, our findings indicate that Rab32 increases dramatically in neurons and macrophages/microglia localized within active MS lesions and that high amounts of Rab32 coincide with the expression of CHOP. In contrast, chronic MS lesions show Rab32 predominantly in neurons.

Simmen and his colleagues were quick to note that it’s not yet clear what actually causes the surge of Rab32. They also note that Rab32 is likely not the only important protein when it comes to unraveling the mystery of MS.
Rab32 is just one of the proteins that is having the effect of drawing the ER and mitochondria too close. There are dozens of other possibilities,” he said.
link


So,  as we learn when digging a bit deeper into the research, it's not just about the increase of Rab32.  This just makes a great headline, and will fund ongoing research for these labs.  But there are other unfolded proteins causing cellular disruption.

At the center of this "discovery" is the endoplasmic reticulum (ER) and ER stress.  The ER is a membraneous structure of a cell, it connects to the nucleus and provides a protective and cleansing function.  Red blood cells do not have ERs...but the liver or pancreas cells have lots of them.  So does the brain.  This is because the ER allows for protein synthesis. And we've known about ER stress in other disease for quite a while.  So, to catagorize this as a "discovery" is not really true.  It's just new for MS researchers to look at how ER stress is linked in Rab32 increases in the MS brain.

The link of ER stress and neurodegeneration is not new.
The ER stress-associated cell death pathways have been recognized in the numerous pathophysiological conditions, such as diabetes, hypoxia, ischemia/reperfusion injury, and neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and bipolar disorder.
link

Under various pathological conditions, the perturbation of any of the three physiological functions of the ER results in so-called ER stress and can lead to an accumulation of the newly synthesized unfolded and misfolded proteins in the ER. Among the stimuli that promote ER stress are ischemia, inflammation, and disorders that impair the ER’s ability to properly fold polypeptides or eliminate unfolded proteins ().
link

Thanks to the work of vascular researchers, we know a few things which can create ER stress.  I suggest reading this complete paper.  link
But to summarize:

ER Stress, Endothelial Dysfunction and unfolded protein response are caused by:
1. High levels of homocysteine
2. Disturbed blood flow and lack of good shear stress
3. High levels of bad cholesterol (LDL) and low levels of good cholesterol (HDL)
4. High levels of glucose
5. High blood pressure and obesity

All the stuff mentioned in the Endothelial Health Program.
link
There are things you can do today to improve health and reduce ER stress.


A final thought for blog readers---targeting one misfolded or rogue protein without considering the mechanism which leads to this perturbation may not be the most successful approach. This is my main concern, and why I wrote this post. We have learned this through years of Alzheimer's research and treatment targeting the beta amyloid protein, which still has no success in alleviating the disease process. In contrast, a multimodal lifestyle approach employed at UCLA led to Alzheimer's disease reversal. link

Big picture: why do cerebral hypoperfusion, cerebral endothelial cell aptosis, a breakdown of the blood brain barrier, ER stress and neurodegeneration occur? 

Continue to dig deeper, past the MS News headlines.
There is truth beneath all of the hyperbole.

Joan















Monday, March 20, 2017

Fast Mimicking Diet (FMD) for MS

In the name of research, and with a bit of curiosity,  I tried a fast.   I've recenly completed the ProLon Fast Mimicking Diet.    More details about the specifics later, but first, you may well be asking---why would someone who LOVES food (yes, a lot link) voluntarily go on a five day fast?   Believe me, I asked myself the same question.

Honestly, I wanted to check out the program before sharing more research with you all.  I really think this is an interesting approach for MS, as it potentially reduces inflammation, boosts cellular rejuvenation, and resets the immune system.  This program has had great success for patients with diabetes and cancer, as well.  It's beginnings were in anti-aging therapies, and clinical trials in many chronic conditions related to aging are ongoing.

Fasting is not something people with MS should do without a doctor's supervision.   I had to get approval from the ProLon nurse (over the phone) before starting the program---and I'm healthy.  People with MS will need even further approval from their doctors, which is a really good thing.  But it might be worth exploring.  You can take the research and links to your doctor and see if this might be right for you.   Jeff said he's interested after watching me last week, so we'll clear it with his doctor and do it together later this year.

Here's the science.  In 2016, a study at the University of Southern California researched fasting and multiple sclerosis, and found that caloric reduction with a fast mimicking diet (FMD) did all sorts of wonderful things for the body, which specifically helped those with MS.

The USC study in mice with EAE and humans with MS found that a fast mimicking diet (FMD) made the body produce more of the hormone corticosterone, which in turn killed off damaging and inflammatory immune cells, and led to a production of new, healthy stem cells.  This study also saw regeneration in myelin producing cells, and reduction of MS symptoms.  All amazing stuff!  Here's more on his study in layman's terms   link    Here is the complete paper, which I suggest reading, and sharing with your doctor if you're interested.    Cell Reports FMD in MS publication

It's potentially an affordable alternative treatment for MS --so get ready for pharma to try and take it down with their own "trials" ( link to "Pragmatic Trial" of fasting with Tysabri )  You know something is worthwhile when pharma gets involved in debunking.

The lead USC researcher, Dr. Valter Longo, also discovered that fasting does not necessitate complete avoidance of food, but a fasting state can be reached by restricting caloric intake in a specific manner.  Thus the "fast mimicking" part.   This is something which might be easier for most of us to accomplish, and this was a key point for me.  I could never do a liquid fast.  I simply get too light headed and tired from low blood sugar.  But I found this program to be much different, and very doable.

I'd had some nice back and forth e-mails with Dr. Longo when this research was first published last year.  We both share a love of music and medicine.  He was a young music student in Italy before coming to the states to study jazz guitar.  He became interested in the study of aging, and got his PhD in biochemistry at UCLA, then joined the USC Davis School of Gerontology.  He is also Director of the USC Longevity Institute.  His focus is on how caloric restriction and fasting kills damaging cells while inducing healthy stem cell production.    link to Dr. Longo's story

I had wondered if any of his FMD studies had looked at markers of inflammation related to endothelial improvements.  I had found prior research looking at this connection.  link  He replied that his group wasn't looking at that specific aspect. He felt that the benefit of FMD was more about reduction of damaging autoimmune cells and a rejuvination of stem cells. But I have a hunch the increase in cortisone is also helping strengthen endothelial cells and reduce cell permeability--as well as helping the microbiome.   The FMD has been shown to reduce C reactive protein in other studies, so there is a vascular connection. I hope more research will be done on these other aspects of the program.

Since I wanted to remain impartial in my analysis of Dr. Longo's FMD, I didn't ask him for a sample.  I purchased the $300 ProLon FMD for myself online.  (Still can't believe I shelled out big bucks to starve myself.)  I hoped for benefit.  I have some pain from a bit of osteoarthritis in two fingers and my neck, and lowering inflammation might help me.  Losing weight wasn't my primary objective, but I figured it would be a nice side effect.  I'm turning 55 this week,  and my vanity continues.   Jeff and I already follow the Endothelial Health Program.  We eat whole, organic foods, mostly plants and no processed food, no dairy or gluten, so I was already in the right dietary zone.  Just had to halve my daily caloric intake.  Gulp.

The things I liked about ProLon were that it is a plant based and gluten free diet, shipped in a box right to my front door.  It was very easy to follow.  Each day had a separate carton, which was clearly labled with nutritional information and instructions.  You can learn more about the specifics of this diet here:   https://prolonfmd.com   The reason it is a five day fast is because it takes that long for the body to reprogram and for cells to rejuvenate.  Dr. Longo recommends doing this fast every three to four months.  I think I could handle it a few times a year.

I believe it would be pretty easy to hack this program and do it on my own now.  I have all of the caloric and nutrient info.  But it's nice to have the supplements and energy drink and everything timed and packaged.  Makes it easier to follow,  and you're less likely to stray, when you think about how much you spent.   The food was surprisingly palatable.  I loved the kale crackers, and the instant soups were hearty and filling.  The breakfast bar was nutty and satisfying to chew.  Olives for snacks was fine with me.  And the herbal teas were nice.   I felt better knowing Dr. Longo is donating the proceeds to charity.  He's a good guy.   Anyone who studies jazz guitar and wants people healthier without drugs is OK in my book.   link

How did I feel after 5 days of eating under 800 calories?  It's odd, I wasn't really hungry, except for one day.  I was surprisingly energized, and not fatigued.   The hardest part of this program was giving up my usual three cups of caffeinated coffee a day.  Prolon allows only one caffeinated drink per day, and this left me with a nasty caffeine withdrawal headache after day 1. However,  I didn't feel sluggish without the coffee and I guess that must be from the cortisone coursing through my body.   I was really hungry on day 3, and wanted to quit, but curiosity kept me going.  That, and a bit of pride.

Jeff said he felt guilty eating in front of me.  But he got over that and ate just fine!  I also had to prepare a big dinner for some friends who happened to be in town on Day 2,  and that was pretty hard.   Standing over the stove, cooking and serving a delicious meal and then sitting and watching eveyone happily eating while I sipped herbal tea is not something I want to do again.

Now for the good stuff.  I slept really well, and am still having very vivid, lucid dreams.   I wake up ready to go, not groggy at all.   And my skin looks great!  It could be the fact I didn't had any alcohol, sugar or animal products for 5 days, but my eye bags are less noticeable and my complexion looks rosy.  And my arthritis pain is much, much better.  My knuckles are less stiff, and my neck has been feeling great.  I was able to keep active, out walking, running errands and doing my normal routine, without feeling faint. I didn't have any recording or performing work during this week, so I could take it relatively easy.  And I lost three pounds!  Not as much as many others report (average loss is 5 lbs.) but hey, I'll take it.

Final thoughts.  What we eat matters.  Our bodies are miraculous machines, and it makes sense that the manner in which we fuel ourselves has repercussions on our health.  By putting the body in a fasting state, we kick it into survival mode.  We were created to withstand periods with limited caloric intake, and our body knows how to utilize our stored sugars and fats reserves. Most of us in the industrialized western nations eat much more than we need, far too many processed foods,  too much animal protein and sugar,  and not enough plants.

But this isn't to cast blame for being sick!  No one gives themselves MS, cancer, osteoarthritis, or Alzheimer's.  We don't control our genetic predispositions, and we all will die eventually.   Here's Dr. Longo's TedX talk about how "if one disease doesn't get you, another one will!"   He shows that it is possible to live longer, healthier lives.  link   There are things in our control which we can do to feel better, function better, and maybe even heal,  including fasting. I believe the future will provide more understanding of our microbiome and brain, and how they are connected via the thousands of miles of lymph and blood vessels which keep our organs protected, nourished and cleansed.  And a lot of that depends on food.

Also, as it is the Lenten season, I couldn't help but feel more meaning to the fast.  Christians are taught to fast or give up something during Lent, to remind ourselves of Christ's forty days of fasting, praying and temptation in the desert before his eventual arrest and crucifixion.  This is practiced, not as an exercise in self-denial, but in order to draw closer and more reliant on God. And for that reminder, I am thankful.

Joan