The Gut Brain Connection

Gut Brain Connection

Hippocrates said “All diseases begin in the gut”!

Our western culture’s love of processed foods, the use of antibiotics in our dairy and meats and GMOs have led to a destruction of our friendly gut flora. Pain relievers, such as aspirin and NSAIDS, and steroids also damage the gut flora. Birth control pills, sleeping pills, GERD medications and numerous other drugs cause problems within the GI tract.

Eating a diet filled with too much simple carbohydrates, sugars and processed foods increases the fungi that live in our gut flora. If the fungi and “bad bacteria” outnumber the beneficial bacteria we are prone to develop disease.

 According to Natasha Campbell-McBride MD, neurologist and author of The Gut and Psychology Syndrome, there are dietary measures for restoring a healthy gut.  She recommends taking a probiotic supplement and a diet that includes food sourced probiotics from fermented foods and water and milk kefirs.

Eating fermented foods on a regular basis is the most effective way to heal a “leaky gut”, a condition that exists because of a weakened and often inflamed, permeable intestinal membrane, which allows undigested food particles to enter the blood stream.

The science is there, we are what we eat and we can heal ourselves with the help of fermented foods.

September FDA Update

We had expected to receive a response from the FDA the day after Labor Day but did not. David called  the FDA on September 3rd and spoke to one of the reviewers who was very friendly. She said we were down to minor issues and sent the document to us.  This latest deficiency notice focused on the frequency of adverse events noted in the literature and, once again, said they recommended but do not require a sham control group. Once again, we explained that patients had to pay for this treatment themselves and were certainly not going to pay for a sham treatment.  David called the agency again to ask why they keep asking the same question each month and the reviewer he spoke to said they understood that we couldn't provide a control arm but "we're required by congress" to mention study design considerations in all correspondence.

Of course a double blind placebo controlled trial  is the only way to prove once and for all if venoplasty helps MS patients but this is a very difficult and expensive study to do.  We sympathize with Dr Siskin that he had difficulty recruiting subjects who might only get a sham procedure.

 Our philosophy with the Registry is to continue collecting data and improving venoplasty technique under the auspices of the FDA to keep up the momentum until such a double blind placebo controlled study can be done.

Here is a very brief summary of where we stand with the FDA:

 It's not funded, patients or their insurance must pay for the procedure.  There are ultrasounds before and at 1 week and 1, 6 and 12 months.  The FDA is also allowing only one brand of stent under clearly constrained circumstances, and requiring that patients have an EDSS score before and at 12 months.  Otherwise it's pretty straightforward quality-of-life and adverse event form completions.  Approximately 100 people have expressed interest in participating and a group of very experienced interventional radiologists around the country are waiting to begin ( we're not posting their names yet until they have a chance to review the final FDA requirements).

Decrease your inflammation

Inflammation Information 

The evidence seems incontrovertible that low grade inflammation weakens the brain endothelium and promotes neurodegeneration. For a thorough review see Dr David Perlmutter’s article:

The Role of Inflammation in Neurodegenerative Disorders: Integrative Approaches to Challenging Neurological Disorders

 http://www.worldhealth.net/pdf/bookstore/aamt_vol7_30_perlmutter.pdf

Dhttp://drperlmutter.com

An anti-inflammatory diet and lifestyle change (stress reduction, exercise, gluten free/Paleo diet) are critical for endothelial health. Anti-inflammatory foods help to keep the immune system in balance and not over-inflame when stimulated. To effectively decrease inflammation it is essential to  completely avoid man-made foods, sugars, gluten and food allergens.

 Anti-inflammatory foods include, but are not limited to coconut products, berries, and non-denatured, whey protein from grass-fed cows and goats. Anti-inflammatory herbs such as turmeric, ginger, boswellia, cinnamon, rosemary, & oregano among others should be used as much as possible.

Naturally fermented foods such as red cabbage sauerkraut, kimchi, & coconut kefir are excellent foods for restoring healthy gut bacteria.which is essential in decreasing inflammation.  Additionally, a high quality probiotic supplement with 50+ billion microorganisms should be consumed regularly.

http://www.naturalnews.com/038915_inflammation_foods_healing.html

A balanced immune response in the body is also dependent upon healthy vitamin D levels. Vitamin D helps the body recognize between foreign and self proteins. This reduces inflammation and auto-immune reactions.Healthy Vitamin D3 levels should be between 60-100 ng/ml. Be sure to get tested and supplement if necessary.

The Hubbard Foundation believes that people should be tested for low grade inflammation. These are some tests you might consider:

Vitamin D…25(OH)D

http://www.vrp.com/single-vitamins/vitamin-d3-deficiency-linked-to-a-surprising-number-of-health-concerns

Oxidized LDL

http://cholesterol.about.com/od/lipoproteins/f/oxidizedldl.htm

High sensitivity C-reactive Protein

http://www.nlm.nih.gov/medlineplus/ency/article/003356.htm

Homocysteine

Here’s some more information:

http://drbenkim.com/articles-homocysteine.html

To help decrease inflammation we recommend the use of Tumeric (curcumin is the main anti-inflammatory component of Tumeric).

http://www.ncbi.nlm.nih.gov/pubmed/12676044

You can make a delicious tea which you can drink hot or cold throughout the day:

Add the juice of a lemon or lime to a cup of hot water. Add a few slices of fresh ginger, a sprinkle of turmeric and cayenne with a little bit of Stevia ….if you like your tea sweet.

In addition, you can add some supplements such as:

Nrf2 activator

Omega 3

Neprinol (systemic enzymes which help to thin the blood by removing fibrin)

Astaxanthin

We also recommend eating lots of dark colorful vegetables, grass fed beef, free range chicken and eggs. Ridding your diet of simple carbs like rice, pasta, bread and sugars you can reduce inflammation.

We  believe being under the care of an integrative medicine, functional medicine or naturopathic doctor can be of great benefit.

To find a naturopath near you go to:

www.acam.org

Here are some links for more information:

http://www.naturalnews.com/038915_inflammation_foods_healing.html

http://www.greenmedinfo.com/blog/are-mental-disorders-result-neuroinflammation

http://www.collective-evolution.com/2013/05/30/new-study-shows-cannabinoids-improve-efficiency-of-mitochondria-and-remove-damaged-brain-cells/#_

http://www.greenmedinfo.com/article/stevia-anti-inflammatory-and-immunomodulatory

Responses to comments on our June Newsletter

As most of you know we have been negotiating with the FDA since their warning letter in May 2012 to get their approval to continue our Registry which had already enrolled over 400 MS patients receiving venoplasty.  In their most recent request for revisions they have asked that we add EDSS scores before and one year after the treatment.  We agree that this is an additional burden and that EDSS scores are incomplete and inaccurate. However, we have no choice and, at least ,in the United States these neurology evaluations should be covered by insurance.  We are aware that most insurance is presently not covering the venoplasty itself and patients will have to pay for this themselves.  We have approximately 6 IRs that have been waiting to begin doing the procedure again when we get approval. They are listed on our web site where you can also let us know if you might be planning to participate. www.hubbardfoundation.org/participating-irs

Dimethyl Fumerate update

This week's Neurology Today published a story on PML in patients taking dimethyl fumarate.  There have been a total of 4 patients in Europe.  Each of the patients had severe and prolonged lymphocytopenia - low lymphocyte counts in their blood.  All of them recovered after being taken off fumarates.  Severe lympocytopenia occurs in 3% of patients taking fumarates.  One of the patients had also been treated with methotrexate, another with steroids.  Robert Fox MD interviewed for this story thought that either infection or a significantly altered immune system might be the culprit rather than the fumarate itself.  The cause of lymphocytopenia is not yet known, especially since the mechanism of action of fumarates is suppression of oxidative stress, not immunosuppression per se.

Dr Hubbard has been communicating with David Perlmutter,MD http://www.DrPerlmutter.com/ regarding the dosage of Nrf2 activators with those with neurodegenerative disease. Dr. Hubbard is concerned that only one or two tablets per day of the supplemental forms of fumarate derivatives is too low a dose for MS patients.Both Drs Hubbard and Perlmutter are  suggesting patients push the dose to three or four tablets per day, or even to the point of getting some flushing or nausea (common with Tecfidera) and then backing off a until they feel better and that would be the working dose.

Dr Perlmutter also suggested that instead of increasing the Nrf2 activator (Protandim or Xymogen Nrf2 activator) patients may add more Turmeric and Sulforaphane along with the product.

When you are making any changes to your medications or supplements you should always consult with your trusted medical professional.

Brain Healthy Decadence

Cacao Hazelnut Brain Bliss

Nearly all of the ingredients in this decadent spread are beneficial for brain function. Check out the notes below for more information!

*2cups Hazelnut Butter

1/3 cup cacao

1/3 cup coconut oil

20-30 drops Hazelnut Stevia (if you only have plain liquid Stevia that should be fine)

pinch of salt

Place all ingredients in a food processor and blend.

Enjoy as a fruit dip, spread or the way I like it….by the spoonful!

Hazelnut butter

1lb raw hazelnuts.

Preheat oven to 350°

Roast for 10-15 min on a sheet pan.

When cool, place in food processor with a pinch of salt. Blend until smooth.

Benefits of Hazelnuts:

 Hazelnuts are rich in vitamin B6 which is necessary for nervous system function. In addition,B6 is necessary for the creation of myelin, the insulating sheath of the nerve that increases the speed and efficiency of electrical impulses, allowing the nervous system to operate optimally. What's more, vitamin B6 is instrumental in the synthesis of the neurotransmitters serotonin,

melatonin, and epinephrine.

Benefits of Coconut Oil:

There are numerous benefits of coconut oil (too many to explain here).

“There's another substance that can feed your brain and prevent brain atrophy. It may even restore and renew neuron and nerve function in your brain after damage has set in.

Ketones are what your body produces when it converts fat (as opposed to glucose) into energy. And a primary source of ketone bodies are the medium chain triglycerides (MCT) found in coconut oil!

http://www.healthdiaries.com/eatthis/8-health-benefits-of-hazelnuts.html

Coconut oil contains about 66 percent MCTs.”

http://www.naturepacific.com/contents/en-us/d227_virgin-coconut-oil-brain-food-prevent-Alzheimers.html

Benefits of Cacao:

“Flavanols may act on the brain structure and function directly by protecting neurons from injury, improving metabolism and their interaction with the molecular structure responsible for memory researchers said. Indirectly, flavanols may help by improving brain blood flow.”

http://www.sciencedaily.com/releases/2012/08/120813173205.htm

FDA announces approval of dimethyl fumarate

Dimethyl Fumarate

On March 27, 2013 Dimethyl fumarate has won FDA approval to treat relapsing-remitting forms of multiple sclerosis and will be sold under the name Tecfidera also known as BG-12, manufactured by Biogen Idec.

The drug has been used for many years in Europe to treat psoriasis, and since the 1980’s as a fungicide.

Dimethyl fumarate is unlike all previous MS “disease-modifying drugs” (DMDs) which all work by eliminating T lymphocytes and/or preventing them from crossing the blood-brain barrier.  It thus represents a “radical change in multiple sclerosis pathogenesis” according to van Horssen a long-time leading MS researcher.  Instead, dimethyl fumarate is an “anti-oxidant” which means that it reduces “reactive oxygen species” which in turn reduces free radicals. For years health specialists have been extolling the importance of anti-oxidants such as green tea and turmeric to delay ageing.  But recent research has demonstrated that the oligodendrocytes that make myelin are extremely sensitive to free radicals. Dr. van Horssen reported at ECTRIMS in 2011 that dimethyl fumarate exerts its protective effect via activation of the nuclear-factor-E2 (Nrf2) transcriptional pathway that is involved in the production of antioxidant enzymes necessary for oxidative stress defense.  He stated that distinct Nrf2 activators like dimethyl fumarate boost antioxidant enzyme production in oligodendrocytes and limit ROS-mediated oligodendrocyte death.

Two placebo-controlled phase III trials served as the basis for the FDA approval.  A total of about 2,700 patients were studied. In addition to comparing the drug with placebo, dimethyl fumarate was also compared to glatiramer acetate (Copaxone).

At the 2013 annual meeting of the American Academy of Neurology Robert Fox, MD reported that MRI T2 lesions were reduced by 72% at 6 months and 82% at two years.  Gadolinium-enhancing lesions were reduced by 83% at 6 months and 83% at two years.  This is much better than the immunosuppressants drugs.  It was also superior to Copaxone.

The main side effect was gastrointestinal complaints.  There has also been a case report of one 72 year-old man who developed PML on Fumaderm the name of the drug in Germany that has recently been purchased by Biogen.

Biogen obtained a use patent for dimethyl fumarate in 2009.  It is important to note this was a “use” patent; Biogen did not invent dimethyl fumarate that has been available for decades.  They patented the preparation of it in enteric-coated micro-tablets to reduce the GI irritation in a dose designed to deliver approximately 100 mg of fumaric acid to treat multiple sclerosis and other conditions.

Dr. van Horssen also compared Biogen’s formulation called BG-12 to Protandim, an over-the-counter Nfr2 activator dietary supplement in an in vitro (human oligodendrocyte cells in a petri dish, not in vivo, skeptical and gullible human beings).   He found that Protandim was actually superior to BG-12, as the “most potent induction of Nfr2-driven antioxidant enzyme production in oligodendrocytes” (ECTRIMs 2011).

Biogen recommends taking the 120mg capsule twice daily, increasing to two (2) twice daily after a few weeks.  Based on their 2009 patent this would be approximately 100mg of fumeric acid, but we are still looking into this conversion question.  Although Biogen has not announced how much they will charge for their new drug, it is likely that it will be about the same as the other DMDs, i.e. about $40,000 per year.  Protandim is expensive but costs about $40 per month or $480 per year, but currently will not be reimbursed by insurance companies.  It contains several herbs that are high in fumeric acid including green tea extract and turmeric extract.  The company that makes Protandim typically recommends one tablet a day.  David Perlmutter MD (author of “BrainRecovery.com”) recommends that patients with neurodegenerative disorders such as MS take one twice daily of  another brand of Nfr2 Activator made by Xymogen which also contains green tea and turmeric extracts.  One can take the herbs themselves but it will be important to make sure that an adequate quantity is taken and there may be more GI irritation at higher doses. Terry Wahls MD (author of “Minding My Mitochondria”) recommends 3 cups per day of intensely colors vegetables and fruits such as beets, carrots, squash, berries and peaches. Non-denatured whey is also a source of anti-oxidant stimulation.  Ann Boroch CNC (author of “Healing Multiple Sclerosis”) also recommends anti-oxidants ideally from foods but also several supplements including  Antioxidant Supreme made by Gaia Herbs.  We are continuing to look into the appropriate conversion between Tecfidera and other formulations.  Since Biogen has spent many millions to prove dimethyl fumarate’s efficacy, it will be worthwhile to try to obtain adequate quantities of similar Nrf2 activators from other formulations.

Summary:  A multi-million dollar FDA trial has proven that taking Nfr2 activators dramatically reduces MS.  The mechanism of action is the reduction of oxidative stress, not immunosuppression.  This mechanism is in keeping with the inflammation/brain vein drainage model (in contrast to the orthodox autoimmune attack on intact myelin by T cells model).  We believe that everyone should be taking it, whether prescribed by neurologists – Tecfidera, or by naturopaths – Protandim, Xymogen, diet, or herbal supplements.