Mast Cell Activation Syndrome (MCAS): When Histamine Goes Haywire...

Mast Cell Activation Syndrome (MCAS): When Histamine Goes Haywire...

Mast cells are present in most tissues throughout the human body, especially connective tissue, skin, intestinal lining cardiovascular system, nervous system, and reproductive organs. They are part of the allergic response designed to protect us from threat and injury.  When the body is exposed to a perceived threat, the mast cells secrete chemical mediators, such as histamine, interleukins, prostaglandins, cytokines, chemokine and various other chemicals stored in the cytoplasm of the cell.  These chemical messengers produce both local and systemic effects, such as increased permeability of blood vessels (inflammation and swelling), contraction of smooth muscle (stomach cramps and heart palpitations), and increase mucous production (congestion, sneezing, etc).   Historically, we thought of mast cells only in relation to an allergic or anaphylactic response.  We now know they play a profound role in immune activation, development of autoimmunity and many other disorders, such as POTS (postural orthostatic tachycardia syndrome).  Sadly we are seeing a large increase in patients presenting with mast cell disorders and MCAS.  I believe it is in part do to the onslaught of more pervasive environmental toxins, molds and chemicals.

Withouts mast cells, we would not be able to heal from a wound.  They protect us from injury and help the body to heal.  Unforunately, overactive mast cells can cause a variety of serious symptoms.

Symptoms of overactive mast cells may include:

• skin rashes/hives
• swelling/edema
• flushing
• itching
• abdominal pain
• nausea/vomiting
• diarrhea
• wheezing
• shortness of breath
• heart palpitations
• anxiety, difficulty concentrating
• headaches
• brain fog
• low blood pressure
• fatigue

Mast cell activation syndrome (MCAS) is a condition symptoms involving the skin, gastrointestinal, cardiovascular, respiratory, and neurologic systems. It can be classified into primary (clonal proliferation or mastocytosis), secondary (due to a specific stimulus), and idiopathic (no identifiable cause). Proposed criteria for the diagnosis of MCAS included episodic symptoms consistent with mast cell mediator release affecting two or more organ systems with hives, swelling, flushing, nausea, vomiting, diarrhea, abdominal pain, low blood pressure, fainting, heart palpitations, wheezing, red eyes, itching, and/or nasal congestion.  For a diagram of all of the varied symptoms histamine can cause, click here.

Triggers may be medications, foods, supplements, hormones, opioids, stressors (physical or emotional), cold temperature, heat, pressure, noxious odors, chemicals, insect bites, trauma or environmental toxins.

We commonly see mast cell activation syndromes associated with CIRS (chronic inflammatory response syndrome) in response to biotoxins, such as mold, inflammagens, and lyme-related toxins.

 

Low MSH and Mast Cell Disorders?

As mentioned above, we frequently see histamine intolerance and MCAS in patients with mold-related CIRS (chronic inflammatory response syndrome).  It is interesting to note that a common finding in CIRS is low MSH.  According to this study in the Journal of Investigative Dermatology, alpha-MSH plays an immunomodulatory role during inflammatory and allergic reactions of the skin.  In addition, there is evidence that MSH induces mast-cell apoptosis (cell death).

 

Definition of Mast Cell Activation Syndrome (MCAS)

1. Typical clinical symptoms as listed above
2. Increase in serum tryptase level or an increase in other mast cell derived mediators, such as histamine or prostaglandins (PGD2), or their urinary metabolites,
3. Response of symptoms to treatment

Mast cells can be activated by both direct and indirect mechanisms as a result of exposure of the host to pathogens.

Diseases Associated with Mast Cell Activation Syndrome (MCAS)

• Allergies and Asthma
• Autism
• Autoimmune diseases (Hashimoto's thyroiditis,  systemic lupus, multiple sclerosis, bullous pemphigoid, rheumatoid arthritis and others.Eczema
• Celiac Disease
• Chronic Fatigue Syndrome
• CIRS (chronic inflammatory response syndrome)
• Eosinophilic Esophagitis
• Fibromyalgia
• Food Allergy and Intolerances
• Gastroesophageal reflux (GERD)
• Infertility (mast cells in endometrium may contribute to endometriosis)
• Interstitial Cystitis
• Irritable Bowel Syndrome (IBS)
• Migraine Headaches
• Mood disorders - anxiety, depression, and insomnia
• Multiple Chemical Sensitivities
• POTS (postural orthostatic hypotension)

Mast cells are known to be the primary responders in allergic reactions, orchestrating strong responses to minute amounts of allergens. Several recent observations indicate that they may also have a key role in coordinating the early phases of autoimmune diseases, particularly those involving auto-antibodies.

Lab Tests for Mast Cell Activation Syndrome (MCAS)

• Lab tests specific to mast cell activation for suspected MCAS may include:
  • Serum tryptase (most famous mast cell mediator)
  • Serum chromogranin A
  • Plasma histamine
  • Plasma PGD2 (chilled)
  • Plasma heparin (chilled)
  • Urine for PGD2 (chilled)
  • PGF2a
  • N-methylhistamine
• Tryptase is the most famous mast cell mediator. Serum tryptase value is usually normal in MCAS patients, but sometimes it is elevated.  Tryptase values that show an increase of 20% + 2 ng/ml above the baseline level are considered diagnostic for MCAS.
• Chromogranin A is a heat-stable mast cell mediator.  High levels can suggest MCAS, but other sources must first be ruled out, such as heart failure, renal insufficiency, neuroendocrine tumors and proton pump inhibitor (PPI) use.
• Heparin is a very sensitive and specific marker of mast cell activation.  However, due to its quick metabolism in the body, it is very difficult to measure reliably.
• N-methylhistamine is usually measured in a 24 hour urine test to account for the variability in release over the course of the day.
• Prostaglandin D2 is produced by several other cell types, but mast cell release is responsible for the dominant amount found in the body.  PGD2 is less stable than histamine and metabolized completely in 30 minutes.
• Other less specific mast cell mediators that are sometimes abnormal in MCAS patients include Factor VIII, plasma free norepinephrine, tumor necrosis factor alpha, and interleukin-6.

 

Treatments to reduce MCAS symptoms and lower histamine

• H1 Blockers
  1. hydroxyzine, doxepine, diphenhydramine, cetirizine, loratadine, fexofenadine
• H2 Blockers
  1. Famotidine (Pepcid, Pepcid AC)
  2. Cimetidine (Tagamet, Tagamet HB)
  3. Ranitidine (Zantac)
• Leukotriene inhibitors
  1. Montelukast (Singulair)
  2. Zafirlukast (Accolate)
• Mast cell stabilizers -
  1. Cromolyn
  2. Ketotifen
  3. Hyroxyurea
• Tyrosine kinase inhibitors - imatinib
• Natural anti-histamines and mast-cell stabilizers
  • Ascorbic Acid
  • Quercetin
  • Vitamin B6 (pyridoxal-5-phosphate)
  • Omega-3 fatty acids (fish oil, krill oil)
  • Alpha Lipoic Acid
  • N-acetylcysteine (NAC)
  • Methylation donors (SAMe, B12, methyl-folate, riboflavin)
• Certain probiotics decrease histamine production
  • Lactobacillus rhamnosus and bifidobacter species 
• DAO Enzymes with meals - Xymogen HistDAO or Histamine
• Decrease consumption of high histamine foods (more on histamine-restricted diet)
  • Avoid alcoholic beverages
  • Avoid raw and cured sausage products such as salami.
  • Avoid processed or smoked fish products. Use freshly caught seafood instead.
  • Avoid pickles
  • Avoid citrus fruits.
  • Avoid chocolate
  • Avoid nuts
  • Avoid products made with yeast and yeast extracts
  • Avoid soy sauce and fermented soy products
  • Avoid black tea and instant coffee
  • Avoid aged cheese
  • Avoid spinach in large quantities
  • Avoid tomatoes, ketchup and tomato sauces
  • Avoid artificial food colorings & preservatives
  • Avoid certain spices: cinnamon, chili powder, cloves, anise, nutmeg, curry powder, cayenne pepper

Specific Symptom Treatment in MCAS

(Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options)

• Headache⇒ paracetamol; metamizole; flupirtine
• Diarrhea⇒ colestyramine; nystatin; montelukast; ondansetron
• Colicky abdominal pain ⇒ metamizole; butylscopolamine
• Nausea⇒ metoclopramide; dimenhydrinate; 5-HT3 receptor inhibitors; icatibant
• Respiratory symptoms (mainly increased production of viscous mucus and obstruction with compulsive throat clearing) ⇒ montelukast; acute: short-acting albuterol
• Gastric complaints⇒ proton pump inhibitors
• Osteoporosis, bone pain⇒ biphosphonates, Vitamin D plus calcium
• Non-cardiac chest pain⇒  H2-histamine receptor antagonist; proton pump inhibitors
• Tachycardia⇒ verapamil; AT1-receptor antagonists; ivabradin
• Neuropathies ⇒ a-lipoic acid
• Interstitial cystitis⇒ pentosan, amphetamines
• Sleep-onset insomnia/sleep-maintenance insomnia⇒ triazolam/oxazepam
• Conjunctivitis⇒ preservative-free eye drops with glucocorticoids for brief course
• Elevated prostaglandin levels, persistant flushing⇒ incremental doses of acetylsalicylic acid (50-350 mg/day; extreme caution because of the possibility to induce mast cell degranulation)

References

1. Mast Cell Activation Syndrome, A Review
2. Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options
3. Presentation, Diagnosis and Management of Mast Cell Activation Syndrome by Dr. Afrin
4. Histamine and Gut Immune Mucosal Regulation
5. Dr. Theoharides presents “Mast Cell Disorders”
6. Diagram of Histamine Symptoms
7. Mast Cell Aware
8. A Tale of Two Syndromes
9. Mold Histamine Connection

How the Immune System can Control Your Behavior

If someone you love is experiencing depression or finding less pleasure in social activities, you might want to look deeper.   It is quite possible that hidden infection or inflammatory condition may be causing the changes you observe.  Have compassion...there is often more to it than meets the eye.  I have seen many relationships crumble when one person is suffering from immune dysfunction and social isolation and the other does not see the illness for what it really is.

Our immune system is a powerful force inside each one of us!  This protective system is charged with the job of responding to foreign invaders to keep us in optimal health.  Most of us don't think too much about this system until it is not working correctly.  I treat many patients that suffer from overactive or under-active immune systems due to chronic infections, like tick-borne diseases;  toxic exposures, like mold and mycotoxins; or autoimmune diseases, like multiple sclerosis, lupus or Hashimoto's thyroiditis.  Although many patients understand the important role of the immune system in protection and defense, few people know that it also controls our behavior.  A recent study in Nature discussed the role of cytokines activated when the immune system goes on red alert and the connection to social isolation and autistic behaviors.  It's even plausible that changes in immune function may lead to personality changes!

Sickness and Depression

Perhaps no connection has been more studied than that of immune activation and inflammation and the link to depression.  Systemic infections cause the patient to allocate limited resources, conserve energy and prevent spread of infection.  The resulting sickness behavior is common to most infections, including viruses, bacteria and multi-cellular parasitic infections.  There is a broad spectrum of symptoms – fever, nausea, decreased appetite, malaise, fatigue and achiness – all of which may aid in the fight to conserve resources and increase isolation-type behavior.  In animal models we see sickness associated with a decrease in time  seeking interaction with a other animals as a result of diminished motivation for social exploration.  Symptoms of depression appear after pro-inflammatory cytokines are produced by the body or if they are administered experimentally. The fact that inflammation often leads to later depression suggests a cause–effect relationship.  It indicates that immune activation can precipitate depression. Many symptoms of inflammation-induced depression overlap with sickness behaviors, including fatigue, changes in sleep pattern, lack of interest in daily or pleasurable activities (anhedonia), changes in appetite or body mass and unexplained aches and pains

Inflammatory Cytokines and the Brian

A recent article about inflammatory cytokines and brain signaling discussed inflammation and the brain:

When considering the pathological signaling cascades in immunological disorders of the brain, certain cytokines might be considered of key importance, with their presence determining the course of a particular disease. Interleukin-1 (IL-1), IL-6, IL-17, and TNFα are critical for the pathogenesis of inflammation in certain brain disorders. Targeting these cytokines or their receptors can alter the course of several neurological diseases, but the effects may be beneficial or harmful.

We understand from this article that the inflammatory signals of the immune system (cytokines) have a profound effect on the brain.  Many patients battling systemic inflammatory or autoimmune disorders suffer from an "inflamed brain" and all that goes with it... symptoms like depression, anxiety and insomnia.  The role of cytokines on behavior can be summarized by saying that TNFα (sickness and depression) and IL-1β (sickness) alter behavior by direct actions on neurons of the brain.

Gaba may affect the immune system too...

GABA, an inhibitory neurotransmitter in the brain, has a similar inhibitory effect on the immune system. Antigen presenting cells (APCs) of the immune system have gaba receptors and therefore, gaba can directly inhibit the function of these immune cells. What this means is the neurotransmitter from the brain may have a direct inhibitory effect on the body's immune system.  This article on Gaba and the immune system states....Intricate and reciprocal regulatory relationships exist between the nervous system and the immune system, mediated in part by chemical messengers.

 

Insults to the body, from the outside or from the inside, activate cells of the innate immune system. 

[PHOTO SOURCE HERE]

Seven Reasons a Brain Injury can Destroy Your Gut!

Seven Reasons a Brain Injury Can Destroy Your Gut

According to the CDC, incidence of hospital visits for traumatic brain injury have increased over the past decade.  It is one of the leading causes of disability world-wide.  You may know that the gut and brain are intricately connected but did you know that many people who experience brain trauma often experience resulting gut issues?   The gut problems come from alternations in the gut-brain axis or the communication network between our intestines and our cerebral matter.   When this delicate network is disrupted, it may result in dramatic gastrointestinal dysfunction, chronic pain or even disability.

According to Dr. Kharrazian, there are seven key ways in which traumatic brain injury can alter GI function, each of which may contribute to your chronic gastrointestinal disorders.

1. Autonomic Dysregulation - this occurs when the autonomic nervous system no longer appropriately  controls things that should come automatically, like heart rate, breathing, and gut motility.   If the system becomes overactive to a sympathetic stimulus the result may trigger a chronic pain loop that is hard to control, leading to abdominal pain.
2. Disorders of visceral sensing and processing - Visceral sensing is the gut's way of telling the brain what is going on.   Sensations in the gut such as temperature, pH, contractility communicate with the brain to notify the body what is happening in the digestive system.  Disruption of these sensing circuits is one of the main factors implicated in irritable bowel disorders (IBS).  Brain injury often contributes to a broken communication network between gut and brain.
3. Increase in intestinal permeability (leaky gut) -  After brain  injury the tight junctions that connect the cells that line your gut often become dysfunctional and allow large molecules to enter from the digestive tract into the blood stream.  Normally these tight junctions are protecting you from the large molecules, such as undigested food particles, bacterial parts or other luminal contacts that could cross over into the blood stream.  We know that the increase in intestinal permeability is a key factor in the development of autoimmune diseases, from Hashimoto's thyroiditis to multiple sclerosis.
4. Compromise of intestinal mucosa - Very commonly after brain injury, there is a compromise in the health of the mucosal lining.  We see this in patients in the Intensive Care Unit (ICU) as well... anytime the body is under massive stress, there is a tendency for the mucosa that lines the gut to atrophy and die.  The changes we see are often immediate and occur within minutes after brain injury, severe trauma or infection.
5. Breakdown of the blood-brain barrier (BBB) - The BBB, as it is affectionately known, protects your delicate gray matter from outside chemicals and inflammatory agents that may cause problems if allowed to enter.  After a brain injury, this barrier is often compromised, allowing massive inflammatory triggers inside the brain where they do not belong.
6. Brain Immune Dysfunction  - The Central Nervous System (CNS) controls much of the immune system and the production of inflammatory signaling molecules, like cytokines.  If there is an injury to the signaling mechanism it may contribute to either over-activation or under-activation of the immune system  This can lead to either immune compromise or autoimmune disease, where the body attacks itself.
7. Impaired gut motility - Sadly we see this as a factor in many disorders such as intestinal dysbiosis and SIBO (small intestinal bacterial overgrowth).   The impairment in smooth muscle contractility of the gut mucosa leads to dysmotility. This dysmotility leads stagnation  and alteration in bowel function and even malabsorption.  Ultimately patients may have very severe symptoms related to this problem of abnormal peristalsis in the gut.

Can see how these many mechanisms of action on the gut after brain injury may contribute to chronic pain and dysfunction, not only in the gut but the immune system as well?  Here's some simple things you can do to ensure you will maintain a healthy gut for life!

So What Can I Do to Maintain a Healthy Gut?

1. Eat a variety of colorful organic and local produce
2. Avoid genetically modified foods and glyphosate which contribute to a leaky gut
3. Take a daily multi-strain probiotic to support your microbiome and immune system
4. Eat prebiotic-rich fruits and vegetables to feed your healthy gut bugs
5. Protect your noggin!  Wear a helmet if you are skiing, biking or doing any activity that involves risk of head trauma
6. Try Restore, my favorite new product to restore gut health and heal tight junctions.  Call Amy at #303-993-7910 if you would like more info....

Although we cannot predict or even prevent a head injury, it's important to realize that if it does happen to you, your gut function may be affected.   Start NOW to take steps to develop a healthy gut microbiome in the meantime!

Is a Hidden Infection Causing Your Fatigue?

Are you suffering from unrelenting fatigue that doesn't seem to respond to any intervention?  Perhaps you've asked your doctor to check your thyroid function and it came back normal.  Perhaps you've been testing for iron-deficiency anemia this, too, was normal.  Or perhaps you've been told by an integrative medical doctor that your adrenal function is suboptimal.  Maybe what you haven't thought of is the fact that you could be harboring hidden pathogens in your body that are robbing your energy and stealing your steam!

If basic testing fails to reveal a cause of your fatigue, you may want to have your doctor test for occult infection. More sophisticated investigations can reveal the presence of all kinds of pathogens capable of colonizing the body and evading the immune system.  Some of them include: Parvoviruses, HHV6, Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal infections or biotoxin exposure.  A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi.

Chronic fatigue syndrome is a complicated disorder characterized by extreme fatigue that can't be explained by any underlying medical condition. The fatigue may worsen with physical or mental activity, but doesn't improve with rest.

Chronic fatigue syndrome has eight official signs and symptoms, plus the central symptom that gives the condition its name:

• Fatigue
• Loss of memory or concentration
• Sore throat
• Enlarged lymph nodes in your neck or armpits
• Unexplained muscle pain
• Pain that moves from one joint to another without swelling or redness
• Headache of a new type, pattern or severity
• Unrefreshing sleep
• Extreme exhaustion lasting more than 24 hours after physical or mental exercise

If you see a good medical detective, a physician trained in functional medicine, they can work with you to test for any of these underlying causes of the fatigue,

A study of 375 patients with apparently no cause for their disabling fatigue revealed pathological stimulation of white blood cells with abnormally elevated patterns of natural helper and natural killer cells, important infection fighting agents in the immune system in 53% of patients.  It showed depleted levels of IgG subclass three in 59% of the study population.  More than 50% had circulating immune complexes and many tested positive for ANA antibodies, usually seen in autoimmune diseases like lupus.

Why is it that some patients who get an infection recover and have no fatigue and others may be colonized with pathogens and suffer from intractable lack of energy?

It appears that part of the answer lies in the genetic polymorphisms or variances in our bodies response to infection and inflammation.  For those who develop severe fatigue in response to toxic exposure, like mold or infection, their immune systems respond more robustly to the threat with massive production of cytokines, like IL-ß1 or TNF-alpha.

Moreover, polymorphisms in TNF-alpha,IL-1β, interferons (IFNs), IL-6, and IL-10, acting together or separately can make the severity and response of immune system more profound in response to infection.  Why does this happen?  Well these pathogens can trigger TLR's (toll-like receptors) by either PAMPs (pathogen-associated molecular patterns) or DAMPs (damage associated molecular patterns).  Activation of the TLRs causes a massive cytokine surge that becomes like a domino-effect and keeps on going unrelenting in susceptible individuals, contributing to the inflammation, depression and fatigue.  This vicious cycle of pro-inflammatory cytokines that continue to trigger more inflammation and amplify the cycle, leading to more damage and inflammation.

The initial infection followed by chronic inflammation of the immune system could explain the cause of fatigue in these genetically susceptible individuals.  Some patients also suffer from cognitive dysfunction, memory loss, or brain fog as well.

What are some common hidden infections that may be causing your fatigue?

• Epstein Barr Virus (EBV)
• Cytomegalovirus (CMV)
• Human Herpes Virus (HHV-6)
• Parvovirus (Parvo B19)
• Mycoplasma sp.
• Borrelia Burgdorferi
• Chronic mold and mycotoxin exposure

Chronic fatigue syndrome is just a label.  It's useful to identify a group of symptoms that causes significant fatigue and may affect one's life dramatically causing inability to function or hold a job. It does not represent one clincial entity but the cause may be multi-factorial and different in each individual.  It may share a final common pathway of dysfunctional immune activation and inflammation that keeps on going in a self perpetuating manner (like the Energizer Bunny gone bad!)  From a functional medicine perspective it's important to get to the root cause of the chronic fatigue symptoms and cognitive impairment.   Most of these infections, including the inflammatory response (CIRS) to mold and mycotoxins can be measured by ordering conventional lab testing through a knowledgable practitioner.  Ask your doctor to see if he can help you determine the root cause of your fatigue.  Treating the root cause (or infection in this case) just might give you back your life!

References:

1. The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability
2. A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior

Have you been feeling the pressure to make New Year's Resolutions that you know you won't keep? It's the beginning of another year... a blank canvas on which to write out all your dreams and goals. You may be reminiscing about all the wonderful things last year held for you or perhaps recalling some great loss or regret as well.

This year instead of loading on more pressure and setting yourself up for failure with insurmountable goals that you know you won't achieve, I'm sharing a simple list of eight habits that form the foundation of success for me. If you commit to doing them daily for just thirty days, they may become habits for you, too. Believe it or not, it's really the small daily habits that have the ability to transform your life into what you've always dreamed it could be!

Eight Habits that Changed My Life

1. Show Kindness: Be kind to everyone you come in contact with, from your boss to your barista. Simply appreciate others for who they are, not what you would like them to be or what they can do for you. Find surprising ways to bless others with a unexpected tip or word of encouragement. Put aside your personal agenda and look at interruptions in your day as opportunities to serve others. Bob Goff reminds us how in one of my favorite books, Love Does.
2. First things First: Do your most important tasks first thing in the morning. Start with an intention and prayer and then move on to the tasks that matter most. Don't get caught in the urgent by default like most people do. Be deliberate instead of just responding to the crises that come your way. The classic book by Steven Covey is a great place to start if you want to learn more.
3. Say No: Stop saying "yes" to every request that comes your way. Practice saying "let me think about it" before an automatic yes comes from your lips. I like to process important decisions for at least twenty-four hours and sleep on it before committing. Agree to only what is in line with your main mission. What is your mission? Define what you enjoy the most and do the best and then stick to it. Need help defining it? Read Essentialism... it may change your life!
4. Recharge: Go to bed every night with enough time to get eight hours of sleep and wake up refreshed, preferably early. I am usually in bed by 9pm and will even say no to events that require me to be up past my bedtime as I know it will affect my productivity the following day. It's a standing joke that I may decline an invitation because "it's past my bedtime" but I always wake up refreshed without an alarm at 5am and my most productive, undisturbed hours are before the rest of the world awakes.
5. Move: Make time for activity every day. Try something new....free weights in the morning, yoga at lunch or a leisurely stroll in the evening. Better yet, grab a friend or your spouse and enjoy great company and conversation while you work-out. My husband and I often jog in the mornings. On the way home, we walk and talk, discussing our plans and praying for our day.
6. Enjoy! Find joy in simple things that don't cost you anything at all... a gorgeous sunrise, the sensation of cool grass on your bare feet, a snowflake on your tongue, playing fetch with your puppy, the gentle touch of a loved one, or the smile of a stranger. Many of the things that make our life most satisfying are free!
7. Eliminate! Get rid of what no longer serves you... make a habit of cleaning out closets and other spaces in your home. Without intervention, junk accumulates and wastes our precious brain power and energy. Don't be afraid to give things away, especially things of value. There is no greater joy than sharing what God has blessed you with. This practice will ultimately free you from reliance on material things in your life, too. Need motivation? Check out the Life-Changing Magic of Tidying Up.
8. Practice Gratitude: Perhaps the most powerful habit is gratitude... Be grateful every day and make it a habit, like brushing your teeth. Before you fall asleep, list at least three things you are grateful for every single day. Did you know that the two qualities most predictive of life-long happiness are gratitude and life-long learning? (If the title of this article was "Nine Habits", the next one would be commit to life-long learning so you get a freebie :-) )

None of these things are difficult but they require a change in mindset. Philippians 4:8 sums it up nicely, "Finally, brothers and sisters, whatever is true, whatever is worthy of respect, whatever is just, whatever is pure, whatever is lovely, whatever is commendable, if something is excellent or praiseworthy, think about these things." 

 

Wishing you the BEST year ever!

Low Dose Naltrexone (LDN): The New Treatment You've Never Heard of...

Low Dose Naltrexone (LDN):  The treatment you've never heard of...

Why haven't you heard about this amazing new breakthrough for conditions ranging from autoimmunity to cancer?  Perhaps because as of yet no company has stepped forward with the billions of dollars needed to do a large-scale study on low-dose naltrexone (LDN).  Unfortunately getting FDA-approval for use is not a straightforward process.  With the patent expired, no drug company has been willing to pay such a large sum when they cannot sell the drug exclusively.

However, if you check PubMed, there are currently over 90 studies published on the various uses of LDN, from pain relief, fibromyalgia, Crohn's disease, multiple sclerosis, systemic sclerosis and even cancer.  I have been using this drug in clinical practice with great results for the past several years and I want to tell you about it...

So how does LDN work?

Researchers at The Pennsylvania State University College of Medicine, Hershey, Pennsylvania have discovered the mechanism by which a low dose of the opioid antagonist naltrexone, an agent used clinically (off-label) to treat cancer and autoimmune diseases, exerts a profound inhibitory effect on cell proliferation. We believe that opioid receptor blockade by LDN provokes a compensatory elevation in endogenous opioids and opioid receptors that can function even after LDN is no longer available.

These papers revealed that a short-term opioid receptor blockade with naltrexone (LDN), a general opioid receptor antagonist devoid of intrinsic activity, results in an elevation in production of your own opioids and in response to the blockade. Interference of opioid peptide–opioid receptor interactions for a short time each day (from 4-6 hours) with LDN provided a subsequent window of time (18–20 hours) for the increased levels of endogenous opioids and opioid receptors to elicit a robust functional response: the inhibition of cell proliferation.  In addition many patient report an improved sense of well-being and decrease in overall pain, as one might expect with higher levels of opioid production in the body.

Preliminary Research Abounds for cancer and autoimmune disease

Low dose of the opioid antagonist naltrexone (LDN) is being used clinically off-label to treat cancer and autoimmune diseases, by exerting a profound inhibitory effect on cell proliferation.  LDN is an oral medication, generic, inexpensive, and non-toxic, and has been documented to alter the course of both neoplasias and autoimmune diseases such as Crohn's and multiple sclerosis, making this drug especially attractive as a therapeutic agent.

According to this study in Clinical Rheumatology, Low Dose Naltrexone(LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn's disease, multiple sclerosis, and complex regional pain syndrome. They suggest that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone's better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated.

A study published online in the Cochraine Library in February 2014 discusses using low-dose naltrexone to induce remission in Crohn's Disease.  Although the author conclude there is insufficient evidence to recommend and further research is needed, data from one small study suggests that LDN may provide a benefit in terms of clinical and endoscopic response in adult patients with active Crohn’s disease. Data from two small studies suggest that LDN does not increase the rate of specific adverse events relative to placebo.

In the Journal of Clinical Gastroenterology April 2013, Naltrexone therapy appears safe with limited toxicity when given to children with Crohn’s disease and may even reduce disease activity.

Complex Regional Pain Syndrome (CRPS) is a neuropathic pain syndrome involves glial activation and central sensitization in the central nervous system. This can be a difficult disease to treat and patients suffer greatly with severe chronic pain.   An article in the Journal of Neuroimmune Pharmacology showed positive outcomes of two CRPS patients, after they were treated with low-dose naltrexone, in combination with other CRPS therapies.  Perhaps this is because Low Dose Naltrexone (LDN) is known to antagonize the Toll-like Receptor 4 (TLR4) pathway and attenuate activated microglia.

Link to Fibromyalgia and Autism?

Another article posted online in Discovery Medicine came to the following conclusions:

1. Patients on chronic opioids relate autistically.
2. Autism is a hyperopioidergic disorder.
3. Fibromylagia is a hypoopioidergic disorder.
4. Low opioid tone caused by opioid maintenance or fibromyalgia can usually be reversed with low-dose naltrexone.
5. The increase in the incidence of autism may have been caused by the increase in use of opioids for analgesia during childbirth.

The bottom line is that for disorders that involve low endogenous opioid production, like fibromyalgia and chronic fatigue syndrome, Low Dose Naltrexone may prove to be profoundly beneficial.

A January 2013 article written in Arthritis and Rheumatology concluded that evidence continues to show that low dose naltrexone has a specific and clinically beneficial impact on fibromyalgia pain. The medication is widely available, inexpensive, safe, and well-tolerated.

Motility Agent for Small Intestinal Bacterial Overgrowth (SIBO)

Another novel use of Low Dose Naltrexone has been for aiding motility in SIBO (small intestinal bacterial overgrowth).  Ploesser et al described the use of LDN for aiding the migrating motor complex (MMC) in cleansing the small bowel.  His small study use 2.5mg twice daily in patients with IBS and evidence of SIBO and 4.5mg daily in patients with inflammatory bowel disease.  Approximately 68% of the study patients had improvement in symptoms taking LDN.  According to other research, LDN may have effects on the gut to decrease inflammation, decrease intestinal permeability and stabilize toll like receptors, in addition to aiding motility.

Experimental and Off-label but well tolerated and promising

The use of LDN for chronic disorders is still experimental and considered off-label.  This doesn't stop progressive doctors from prescribing it due to it's safety profile.  The typical dose of LDN is a compounded immediate release tablet from 1.5 to 4.5mg taken at bedtime.   The few reported side effects may be related to opioid blockade at night.  Occasionally patients report anxiety, insomnia, vivid dreaming or nightmares.  There are a portion of patients who already have elevated opioids that may not tolerate the drug. To avoid side effects, I generally start patients on half of intended dose and increase after 7-10 days.  If they still report symptoms, we move the dosing earlier in the day and may still get a beneficial effect.

Low Dose Naltrexone is an oral medication, generic, inexpensive, and non-toxic, and has been documented to alter the course of both neoplasias and autoimmune diseases such as Crohn's and multiple sclerosis, making it an attractive and effective therapeutic agent.

For more on LDN watch my recent interview with Dr. Alex Vasquez ...

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More References:

1. Low Dose Naltrexone Research Trust
2. LDN Clinical Trials 

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Glyphosate Toxicity: What you don't know might kill you!

Glyphosate is the active ingredient in the popular herbicide, Roundup.  Glyphosate toxicity is a big deal and what you don't know just might kill you!  Many people routinely spray their lawns with this chemical unaware of the toxicity.   In the United States, farmer's are applying ever increasing amounts to their crops before harvest. According the the World Health Organization, glyphosate is now declared a "probable carcinogen" which means is may cause cancer.  The industry still asserts that it is totally safe for humans, however, one only needs to look at the data to know that is not the case.  Ignorance may be bliss but I believe we may be on the verge of one of the most toxic man made environmental disasters in history... and unfortunately this chemical is persistent in the environment and human body and not easy to clean up.   France's highest court found Monsanto guilty of lying as far back as 2008 about the toxicity it's popular weedkiller, Roundup.  "The court confirmed an earlier judgment that Monsanto had falsely advertised its herbicide as "biodegradable" and claimed it "left the soil clean" (Read more here)

According to an Article in Nature published March 24, 2015:

Glyphosate is the world’s most widely produced herbicide, by volume. It is used extensively in agriculture and is also found in garden products in many countries. The chemical is an ingredient in Monsanto's weedkiller product Roundup, and glyphosate has become more popular with the increasing market share of crops that are genetically engineered to be tolerant to the herbicide.

California recently became the first state to issue plans to list glyphosate as a chemical known to cause cancer according to EcoWatch.  This is big news and we need to pay attention... the use of glyphosate has nearly doubled from 95 million pounds in 2001 to nearly 185million pounds in 2007, according to the latest  released report form the EPA and who knows how much it's increased sine 2007!  This is likely in part due to the increase usage of Round-up Ready genetically modified crops during that time period.

Dr. Anthony Samsel and Dr. Stephanie Seneff state in their recent article published August 2015:

Glyphosate has a large number of tumorigenic [cancer-causing] effects on biological systems, including direct damage to DNA in sensitive cells, disruption of glycine homeostasis, succinate dehydrogenase inhibition, chelation of [minerals such as] manganese, modification to more carcinogenic molecules, such as N-nitrosoglyphosate and glyoxylate, disruption of fructose metabolism, etc...

Sadly epidemiological evidence supports a strong correlation between the dramatic rise in use of glyphosate on crops and the multitude of cancers reaching epidemic proportions, such as breast, pancreatic, kidney, thyroid, bladder, and liver cancers.

In perhaps the most ironic twist of all, glyphosate has proven highly toxic to the basic phase one detoxification of the liver, the cytochrome pathways.  I find it incredibly alarming that one of the most toxic chemicals known to mankind also exerts it's influence by impairing human detoxification.  Here is an excerpt from  Entropy 2013, Glyphosate's Suppression of Cytochrome P450 enzymes and amino acid biosynthesis by the gut microbe:

Glyphosate's inhibition of cytochrome P450 (CYP) enzymes is an overlooked component of its toxicity to mammals. CYP enzymes play crucial roles in biology, one of which is to detoxify xenobiotics. Thus, glyphosate enhances the damaging effects of other food borne chemical residues and environmental toxins. Negative impact on the body is insidious and manifests slowly over time as inflammation damages cellular systems throughout the body.

Harvesting wheat after glyphosate application

Glyphosate may trigger autoimmunity, such as celiac disease by the following mechanisms:

• Spraying of wheat before harvest with glyphosate, a common practice in North America allows for a large exposure to glyphosate in wheat.
• Wheat may be the most common ingredient in all processed foods.
• Glyphosate also damages the microvilli in gut reducing ability to absorb vitamins and minerals
• Wheat contains gliadin, which is difficult for genetically susceptible individuals to break down.
• Glyphosate may attach to the gliadin as a consequence of a chemical interaction between the chemical make it even harder to break down this large protein molecule.
• It may not be recognized by the body or able to be broken down, making even more likely to induce an immunological response in susceptible individuals, contributing to development of celiac disease

In addition to celiac disease, researchers now believe that glyphosate may be linked to the following diseases:

1. Autism
2. Autoimmune diseases
3. Cancer
4. Parkinson's
5. Alzheimer's disease
6. Inflammatory bowel diseases (Crohn's and Ulcerative Colitis)
7. Cardiovascular disease
8. Depression
9. Infertility

Glyphosate is also toxic to our gut microbiome

Glyphosate is toxic to many of our benetifical gut microbes.  It may preferentially kill off species, like lactobacillus while leaving potential pathogens, like clostridia to run wild.  Glyphosate also chelates essential minerals, such as manganese, iron, cobalt, molybdenum, and copper so that the gut microbes do not have access to them.  This leads to chronic inflammatory states in the gut as well as increased intestinal permeability, a mechanism at the core of many chronic illnesses, including inflammatory bowel disease, depression, and autoimmunity.

If you are eating processed food, you are eating glyphosate...

Residues of glyphosate are commonly found in the most common foods in the American Diet, including

1. Corn
2. Soy
3. Sugar Beets (sugar)
4. Canola
5. Cotton (not food but in clothing, sanitary napkins and many products we use daily)

Nearly one billion pounds of glyphosate are doused on both conventional and genetically modified crops world-wide each year but GMO crops receive the largest amounts.  Processed foods undoubtable expose you to this toxic contamination, courtesy of wheat, corn, soy and the vegetable oil used.  And the meats from conventionally raised animals in confined feed lots are given fed that most likely contains glyphosate-laden corn and soy.

And finally... it gets personal

You may know that I grew up on a farm in Central Illinois.  My Dad and brothers still farm corn and soybeans there and I couldn't be more proud that they have recently switched over to non-GMO versions of these crops.  My brothers have started a few fields of organic crops as well.  Due to my own history of breast cancer and Crohn's disease, I have followed at 100% organic diet for at least the past 10-15 years.  Recently I realized just how pervasive this glyphosate exposure is in our environment when I sent out my urine to test my own glyphosate level.  I was shocked to get the results back (below) showing that my level was higher than the "Farmer" study, which tested farm workers on application day!  This made me realize how pervasive this dangerous chemical is in our environment and how important it is to remain vigilant to decrease exposure and work to get it banned.

Dr. Jill glyphosate levels

Ok, so what can I do about it?!

The most important thing to realize is that you cannot wash glyphosate off food since it is incorporated into each cell of plant.

Here are some tips to keep your diet free of glyphosate:

• Only way to 100% eliminate from your diet is to avoid conventionally grown and processed foods 
• Glyphosate accumulates in animal tissues, so make sure your meat was not fed GMO grains and your butter and dairy is organic
• Switch over to a 100% organic diet
• Take activated charcoal, clay or rice bran powder in aiding elimination of organophosphates and glyphosate after exposure
• Maintain adequate mineral status by taking a multi-mineral supplement that includes trace minerals
• Support glutathione production with N-acetylcysteine, glycine and glutamine or oral liposomal glutathione
• Support phase 1 and phase 2 liver detoxification by avoiding alcohol and taking liver support, like silymarin, lipoid acid
• It is much harder to reverse damage once it's done, so best to avoid glyphosate from the start—especially in children!

So go to it...  It's worth every penny to grown your own food or buy organic and begin to detox your body of this dangerous chemical!