Biotin for Progressive MS

UPDATE:  December 2017---

Medday, the company developing high dose biotin for progressive MS, has told the European Medicines Agency that it wishes to withdraw its licence application for the treatment of progressive multiple sclerosis.The European Medicines Agency (EMA) has been examining data on high dose biotin (MD1003, Qizenday) since the application was accepted in September 2016. At a meeting last week, the EMA's Committee for Medicinal Products for Human Use (CHMP) concluded that the clinical data from two trials that enrolled 253 patients was not sufficient(link is external) to assess the effectiveness or the safety of biotin.  link

Recent research and press releases on the use of super-high dosages of biotin (300 mg a day, also known as MD1003) for progressive MS are all over the internet, after moderate improvements in MS symptoms were announced at the annual American Academy of Neurology meeting last week.  MS boards and patient blogs describe how people are considering trying this therapy on their own, by securing high dosages of biotin from compounding pharmacies or health food stores.   But strangely absent from this online discussion is the method of action implied for biotin, which is targeting the results of a decrease in cerebral blood flow, as well as the actual results of pilot studies.  I think it's vitally important to look behind the MS research headlines, and consider the science.  Especially before investing time, money and hope in a new product.

I simply do not think it's wise to take mega-doses of biotin.  Although I do think it's important to deal with slowed cerebral blood flow in the MS brain.  Please take 5 minutes to read this note, and I believe you might feel the same way.

I first wrote about biotin at the beginning of April, on the CCSVI in MS Facebook page, after one of our administrators posted a link to an abstract.
High doses of biotin in chronic progressive multiple sclerosis: A pilot study.

http://www.ncbi.nlm.nih.gov/pubmed/25787192

Here's what I posted below the link from Sandro:
"Biotin is also known as vitamin B7. It is found in peanuts, leafy green veggies and egg yolks. It is naturally produced by healthy intestinal bacteria. Smoking and drinking can deplete it. Thanks to Sandro for this link.  
All of these ideas can be found in the Endothelial Health Program, which recommends probiotics, B vitamins, dietary increases in leafy veggies, and smoking cessation. It's not a pill, it's a lifestyle. Joan"

At that time, readers were asking for more information, so I dug a bit deeper and found the patent application for this new "drug."
http://www.google.com/patents/WO2014016003A1?cl=en

"A pharma company is patenting this high dosage of biotin, to market this vitamin as a drug. Here's the patent. I suggest you read it, it is enlightening. They are also patenting this "drug" for ischemic stroke damage and hypoperfusion. Drug companies understand the vascular connection."


In fact, if you read the entire patent application, the method of action for high dosages of biotin in multiple sclerosis is explained--biotin is targeting the damage from ischemia.  This vitamin addresses the results of  decreased cerebral blood flow, which creates ischemia, oxidative stress and reduced ATP production in the brain's cells.  From the patent application:

 The major responsibility for the evolution of the ischemic penumbra is the status of local cerebral blood flow. It is assumed that a decrease in cerebral blood flow yields reduced ATP production and failure of Na+/K+ pumps, increasing extracellular glutamate and activating glutamate- mediated channels, ending in an increase of intracellular calcium that is deleterious for the cell. It is widely accepted that the ischemic penumbra is a target for neurorepair and neuroprotective therapies.

Once again, we see quite clearly that drug companies understand the fact that the MS brain is hypoperfused and suffering from ischemia.  They know there is a vascular connection in MS, and that the damage to the MS brain is very similar to ischemic stroke.  

The results of the biotin study were somewhat compelling, but I was surprised at how many people were ready to take high doses of a vitamin, without understanding the mechanism of action, or the fact that this treatment was created for a very specific type of MS--mainly optic neuropathy.  In fact, the major improvements in patients in the trial were not in motor abilities, but in vision.  The changes is EDSS were incredibly minor. All of this information is very specifically addressed in the patent application.

I've often said that it is much easier to placebo control one compound, one drug, one treatment modality at a time, rather than an entire lifestyle. Because of this fact, drug companies are able to test high dosages of biotin in the gold standard method, against placebo,  and publish results.  But this does not mean that the best method of addressing the damage of a hypoperfused brain is high dosages of biotin.

There are side effects noted with high dosages of biotin, and serious interactions with other drugs.

Interactions. Biotin negatively interacts with anti-seizure medications and medications that help lower cholesterol, causing these medications to work less effectively. While biotin is helpful in regulating your metabolism and blood sugar levels, it can have a distinct effect on the overall blood glucose level in your body. If you are taking medications like cholesterol medication or anticonvulsants or treating a condition like diabetes, taking biotin can have an impact on your symptoms.
http://www.md-health.com/Biotin-Side-Effects.html



Best results are found in a complete lifestyle approach, with cardiovascular exercise, physical therapy, whole food nutrition full of leafy greens and phytonutrients from plants, stress reduction, probiotics,  UV ray therapy, vitamin D supplementation, vitamin B supplementation, smoking cessation, hydration, adequate sleep,  and addressing venous malformations which may be impacting cerebral blood flow.

There is no one miracle pill or supplement or drug which can replicate the results of a complete lifestyle.

Here's the complete program I created for Jeff, which takes all of this into account.  It was created to deal with oxidative stress, hypoperfusion and energy depletion in the brain.
http://ccsvi.org/index.php/helping-myself/endothelial-health

The Endothelial Health Program was created to increase cerebral blood flow, via healthier blood vessels and cardiovascular function.  All of the steps are proven, scientifically, to increase cerebral blood flow and oxygenation of the brain.  It is preventative and reparative medicine.  And it works.  Jeff's going strong, now 8 years past his MS diagnosis, with no MS progression and a reversal of brain atrophy on MRI.  He's still jogging and working full days. Always consult with your own physician before beginning a new lifestyle program.  Jeff works with our GP, to make sure all of his blood numbers are good, and that he is doing well on his program.

Be well, be hopeful, but understand that there is not one pill or compound or vitamin that will ever replace a multi-modal, systems approach to healing.

Joan

What has Changed?

In the five years since Dr. Zamboni's first publication on the connection of MS to extracranial hemodynamics, there have been many changes in mainstream MS treatment and new discoveries made by researchers around the world.

The relationship of the vascular system in MS is being explored, and dealt with in a sideways manner by neurologists.  I do not expect we will ever hear that CCSVI is valid science from neurologists--they will attempt to rename it, requantify slowed venous return and hypoperfusion, and make it their own.  They will call Dr. Zamboni's discovery of CCSVI junk science- while they are working on patenting drugs to address blood flow in pwMS.  This is because neurologists work with pharma and write prescriptions.  They do not deal with the mechanistics of the brain's circulation or with the venous malformations Dr. Zamboni has discovered.  They are not phlebologists or vascular surgeons. For MS specialists, this discovery of hemodynamic alterations goes beyond their practical expertise.

However, one neurologist recently published a paper on the vascular connection to MS, and said this:

"...vascular contributions in MS do appear to support the notion of the vasculature being an initiating target in MS etiology and not simply a bystander presentation of other disease processes. Perhaps the strongest support for this is the number of MS therapies that have been developed, which target leukocyte binding to activated endothelial cells, a central component of the blood-brain barrier (BBB)."
http://www.biomedcentral.com/1741-7015/11/219

Here are drugs being developed by neurologists to address blood flow:
http://ccsviinms.blogspot.com/2013/08/medications-for-ms-addressing-blood.html

What have we learned since Dr. Zamboni first began publishing his research on CCSVI?  

1. People with MS (pwMS) have slower cerebral hemodynamics than normal people.  Their blood flow exits the brain at a slower rate. There are hemodynamic differences between normal people and those with MS. Hypoperfusion is real, it opens the blood brain barrier and it damages the brain.  Whether it is a cause or effect of MS will be debated for decades, however vascular researchers have shown better perfusion and cerebral blood flow (CBF) and cerebral spinal fluid (CSF) flow after venoplasty for CCSVI.

http://www.hindawi.com/journals/msi/2013/598093

http://www.ncbi.nlm.nih.gov/pubmed/23523158

2. People with MS do better with exposure to UV rays, which may explain the long-established link of MS rates and northern latitudes. UV ray exposure relieves symptoms in many.  This may be due to increased vitamin D levels, but it might also be due to the way in which UV rays release nitric oxide, change the endothelium and increase blood flow. 

http://ccsviinms.blogspot.com/2013/06/photorelaxation-uv-rays-and-ccsvi-june.html

3. People with MS are being advised to consider their nutrition and to eat more fruits, vegetables and whole foods and less saturated fats and processed foods.   When Dr. Swank suggested this 60 years ago, it was called "junk science" and people with MS were told it wouldn't do them an ounce of good.  It is now given as helpful advice by the NMSS and the AAN.   

Same thing with exercise.  Only a few years ago, pwMS were advised not exert themselves, but to rest and conserve their energy.  Now we know that physical exercise and activity delays progression, and reverses gray matter atrophy.  Same thing with smoking cessation, stress reduction, and better sleep.  All of these cardiovascular lifestyle changes can make a difference.

http://www.nationalmssociety.org/living-with-multiple-sclerosis/healthy-living/index.aspx

4. Oxidative stress and inflammation are recognized as driving forces in MS progression.  This has lead to exploratons of new modalities of treatment, like the Nrf2 pathway. 

http://ccsviinms.blogspot.com/2012/09/oxidative-stress-multiple-sclerosis-and.html

5. Gray matter health has been recognized as a more accurate biomarker of MS progression than white matter lesions.  Gray matter atrophy will become the new target for MS therapies.

http://ccsviinms.blogspot.com/2012/01/iron-and-gray-matter-what-do-we-know.html

6. PwMS have much higher levels of the clotting proteins- fibrin and endothelin-1 in their serum than normals. These are markers of endothelial dysfunction.

http://ccsviinms.blogspot.com/2012/11/whats-blood-got-to-do-with-it-nov.html

7. Upright MRI has allowed us to see how cerebrospinal fluid and blood return to the heart is slowed and impeded in pwMS.

http://www.fonar.com/news/100511.htm

8.  The venous endothelium is being studied, and researchers are noting that there are changes happening to the lining of the veins in people with neurodegenerative disease.

http://www.biomedcentral.com/1741-7015/11/219

9.  CCSVI is being explored around the globe.  There are literally hundreds of papers published in vascular and neurological journals.  New papers come to press every day.  The connection of blood flow and diseases of neurodegeneration continues, as doctors admit that lifestyle interventions and prevention are staving off Alzheimer's and dementia, while none of the drugs have helped one bit.

http://www.ccsvi.org/index.php/component/search/index.php?option=com_search&task=search

10.  The ISNVD has been established.  There is now an international society of researchers working on understanding the venous connection to neurovascular disease.  Their fourth conference will be held in San Francisco in February, 2014.  The International Society for Neurovascular Disease is convening, publishing, and moving this research forward.
http://isnvdconference.org

All of these connections between MS and the cardiovascular system are new.  And this has happened in just the past five years.  

For those waiting for venoplasty to be accepted as an MS treatment, we have to step back and view the other changes that have happened in MS care.  

The American Academy of Neurologists has several papers featured on their page which connect slowed blood flow and neurodegenerative disease.  They have a patient outreach branch--The American Brain Foundation-- and they have a yearly Brain Fair to discuss diet and lifestyle changes people with neurodegenerative diseases, including MS, should consider.  So much for Dr. Swank's junk science.

Here's a wonderful video Christopher Alkenbrack found on Dr. Roy Swank's work.  It was made in 1989 as part of a Canadian news investigation into the success of Dr. Swank's diet in pwMS as compared to a vastly more expensive and failed chemotherapy trial.  If you haven't seen it, it's a must watch.  

Because today, 25 years later, the NMSS is making these very same dietary and lifestyle recommendations to pwMS.  Yet when asked about dietary changes for pwMS, the neurologist in this video from 1989 says there is "little to no benefit."

https://www.youtube.com/watch?feature=player_embedded&v=lEnn_AZT-SU 

When reporters, scientists, neurologists, MS specialists and others say, "Oh, the connection of CCSVI to MS, that's junk science."  We've investigated it, and there's nothing there"---remind them about Dr. Roy Swank.  Remind them how long it took his observations of "capillary fragility", slowed blood flow, increased fibrin and hypercoagulation to be accepted as part of MS.    

He was noting endothelial dysfunction decades before scientists knew about nitric oxide and how environmental factors contributed to blood flow.  And he has never once been credited by mainstream neurology.  You won't see his name or read his research in their journals.  But he was right.

Dr. Zamboni's discovery has revolutionized how we look at cerebral blood flow, by studying the under-researched extracranial venous system, and utilizing doppler ultrasound to understand venous malformations which alter cerebral hemodynamics.  Like Dr. Swank, Dr. T.J.Putnam and others, he is decades ahead of his time.  His discovery of CCSVI may very well be the rest of the equation in understanding the slowed venous return and endothelial dysfunction found in pwMS.   To say that it is junk science, and that there is no connection of venous return in MS, is to negate scientific fact.  

Joan

Oxidative Stress, MS and CCSVI

September 21, 2012 at 9:07am

We've just learned that one target of BG-12/Tecfidera, the new oral super drug /furniture fungicide, and Nrf2 activator from Biogen,  is oxidative stress.  This drug uses the Nrf2 pathway to combat oxidative stress.
link

What is oxidative stress, and how does it impact multiple sclerosis?

I first started reading about oxidative stress when I began researching the Endothelial Health program to help my husband Jeff.  I did this because his blood and body showed signs of oxidative stress.  The following info is from the program. 

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

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

Oxidative stress

Our bodies constantly react with oxygen as we breathe and as our cells produce energy. However, our use of oxygen is a double-edged sword: we need oxygen to survive, but as a consequence of using oxygen, highly reactive molecules, known as “free radicals,” are produced. 

Free radicals are atoms or molecules with electrons which have lost their partner electron, often as a result of our respiratory or metabolic process, or from outside influences. Free radicals can disrupt the balance of nitric oxide, damage the endothelium and leave it overly permeable, allowing toxins to pass into our tissues9. 

In most instances, our body has an adequate supply of antioxidants obtained from food to neutralize these free radicals, but if the body is depleted, or if there are too many coexistent factors, injury to the endothelium and a change in the balance of NO may occur.

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

People with MS have lower levels of antioxidants in their blood.  It's a scientific fact, pwMS have serious oxidative stress.

Oxidative stress in patients with multiple sclerosis.

We have investigated the oxidative stress in the blood (plasma, erythrocytes and lymphocytes) of 28 patients affected with multiple sclerosis (MS) and of 30 healthy age matched controls, by performing a multiparameter analysis of non-enzymatic and enzymatic antioxidants--

 In conclusion, the blood of patients with MS shows the signs of a significant oxidative stress. The possibility of counteracting it by antioxidant administration plus an appropriate diet, might represent a promising way of inhibiting the progression of the disease. 

http://www.ncbi.nlm.nih.gov/pubmed/10609336

Oxidative stress in multiple sclerosis

Accumulating data indicate that oxidative stress (OS) plays a major role in the pathogenesis of multiple sclerosis (MS). Reactive oxygen species (ROS), leading to OS, generated in excess primarily by macrophages, have been implicated as mediators of demyelization and axonal damage in MS. ROS cause damage to main cellular components such as lipids, proteins and nucleic acids (e.g., RNA, DNA), resulting in cell death by necrosis or apoptosis. In addition, weakened cellular antioxidant defense systems in the central nervous system (CNS) in MS, and its vulnerability to ROS effects may augmented damage. Thus, treatment with antioxidants might theoretically prevent propagation of tissue damage and improve both survival and neurological outcome. Central nervous system is particularly susceptible to ROS-induced damage due to the high oxygen demands of the brain and low concentration of endogenous antioxidants.

http://www.ncbi.nlm.nih.gov/pubmed/20120717

There are many more published papers on MS and oxidative stress, and all of the end with something to the effect of ---gosh, we really should have more studies done on how antioxidants help keep pwMS  healthy!  

But no one does these studies, because there is NO MONEY TO BE MADE!!  

You can simply go and eat more fresh fruits and vegetables, take some antioxidant supplements, vitamin D, stop smoking and drinking, exercise and take care of yourself.  

This is what I explained to Jeff when our family started doing the Endothelial Health Program together.  Dr. Terry Wahls, Dr. George Perlmutter and Dr. George Jelinek would tell you to do the same.  

Now---how does oxidative stress fit into the CCSVI scenario?  

Oxidative stress is actually found in all neurodegenerative disease---Alzheimer's, Parkinsons, MS and dementia.  These diseases share two things that contribute to oxidative stress:

1. Iron deposition in brain tissue

http://members.sirweb.org/members/misc/Singh.pdf

2. Hypoperfusion, or slowed blood flow through the brain.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC400214/

So, we can see that pharma is figuring out there's more to MS treatment. They've seen the papers on CCSVI research, hypoperfusion, oxidative stress and gray matter atrophy.  But they will never tell you that in those words, because the want to keep selling you Tysabri, chemotherapies and other immune ablating drugs.  They will, however, figure out a way to sell you a pill that addresses oxidative stress.  

And you can bet your bottom dollar they are working on a drug to increase cerebral perfusion.

That's why we have to share this information, and help each other and those newly diagnosed with MS.  

Because there is hope, but there will be no miracle pill.

be well,

Joan

 Myelin

December 7, 2010 at 12:01pm

Myelin, the insulating sheath around all of our nerves,  is damaged by an auto-immune reaction in stroke, spinal cord injury, neurovascular disease, dementia, and carbon monoxide poisoning.  

This is a fact.

MS is not unique.  The immune system has the same reaction in situations where there is oxidative stress.

Here's some of the research: 

Long term immunologic consequences of experimental stroke and mucosal tolerance
Background
An inflammatory insult following middle cerebral artery occlusion (MCAO) is associated with a predisposition to develop a deleterious autoimmune response to the brain antigen myelin basic protein (MBP)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816867/

The "autoimmune" reaction of t-cells in spinal cord injury ( SCI) 

Previously, we demonstrated that CNS-reactive T cells are activated in SCI [29,30]. Other groups have shown activation of myelin basic protein (MBP)-reactive T cells after experimental and clinical nerve trauma [31,32]. Clinical studies that show increased frequencies of MBP-reactive T cells in SCI and stroke patients provide further evidence of an association between CNS trauma and the activation of CNS-autoreactive T cells.

http://recovery.tamu.edu/journal%20club%20articles/Popovich03.pdf

Myelin basic protein antigens in carbon monoxide poisoning 

We hypothesized that acute CO-mediated oxidative stress causes alterations in MBP and that immune responses to the modified protein precipitate delayed neurological dysfunction.

These findings provide insight into the pathophysiology of brain injury due to CO poisoning. Biochemical and immunological studies indicate that MBP undergoes charge and antigenic alterations. A causal relationship between lipid peroxidation and MBP modifications is supported by colocalization of MDA-adducts.

http://www.pnas.org/content/101/37/13660.full 

In every single one of these instances, antigens (attackers) to myelin basic protein (MBP reactive t-cells) go after the myelin and destroy it. This is considered an "auto-immune" response.

But in stroke, vascular disease, spinal injury, dementia and CO poisoning, the real culprit, ischemia (injury due to low oxygen) and a break in the blood brain barrier is known.  

-No one calls a stroke an "auto immune disease."