Limitations of Traditional Medicine – Observation Three – It’s limited by the implications of genetic determinism

One of the more popular myths in modern medicine is the myth that it is only genes that control your biological expression.  We’re infatuated with the genome. Ever since Crick and Watson discovered the double helix structure of DNA in 1953, we have been led to believe that the gene is responsible for all final disease causation and we can absolve all responsibility. There is some humor in becoming infatuated with genetic determinism when we realize that humans have about 25,000 genes, slightly less than sweet corn and slightly more than a fruit fly!

In his book Biology of Belief, Bruce Lipton debunks the myth that the gene is the brain of the cell. He includes research showing that you can remove your genes for three months—take them completely out of the cell—and the cell will continue to live.  It’s a well-known fact that these genes don’t know how to turn themselves on and off. But Lipton continues to elaborate on this fact by saying that enucleated cells die not because of their genes being removed, but because they have lost their ability to reproduce.  He makes the bold statement that the nucleus (with its DNA) is not the brain of the cell, but its gonad!

Lipton continues to elaborate on the epigenomic influence by quoting much of the research that has emerged in the last fifteen years by a group of epigenome researchers.  There is much evidence that it is not only the genetic influence that is influencing outcome, but what is termed the epigenomic effect on the gene. Epigenome refers to the influence on the gene by something “above” the gene.  Epigenetic research has established that DNA blueprints passed down through genes are not set in concrete at birth. “Genes are not destiny!” Lipton writes.

Lipton is basically asserting that the genes are not some all-powerful, unalterable code.  Your diet, your stresses, your environment, your beliefs, your concepts, your mind, your emotions and even your ancestors experiences are all capable of modifying your unique genetic expression.  The gene is turned on by the epigenome, by either an internal signal in the body or external signal from the environment. It’s not the gene itself. In other words, the gene has control over your final physiological expression, but there are multiple signaling pathways determining whether or not the gene is going to be expressed or not.  The mind has more to do with your genetic expression; the environment has even more; and nutrition has more than anything else. Every time you eat your genes are washed over by a tide of regulatory signals either pro or anti-inflammatory. These environmental influences turn on regulatory proteins that cover the genetic blueprint, which then allows it to be read and expressed.  The control of the regulatory proteins is what is influenced by everything else but the gene itself.

The implication of genetic determinism is that we are powerless to influence outcomes and we might as well relinquish responsibility and resign ourselves to our fate.  I recently had a patient in my clinic who had high cholesterol. She said, “I can’t help it; my father’s genes are responsible.” Assuming that that was the end of the discussion, she reasoned, “I need Zocor or Lipitor,” referring to the cholesterol-lowering medications that she mistakenly thought were her only choice.

This patient had fallen into a fatalistic trap that desperately needed to be debunked.  What was my reply? “Yes, there may be a specific allele on the genome that is the same as your father’s,” I told her. “But it could just as possibly be the way that you live your life, the food you eat, the way you process emotions, the daily stresses and strains you subject yourself to, or the way you react to them. In fact you may have even learned some of these behaviors and habits from your father, and hence you are literally “your father’s child”…not because of genetics, but from behavioral similarities.”

The evidence is now overwhelming that in many diseases such as cancer, heart disease, and diabetes, the epigenetic mechanisms are playing a significant role. Newsweek recently ran a front-page cover with the heading “Diet and Genes.”  In fact, in research by Willet (220), it has been found that only 5 percent of cancer and cardiovascular patients can attribute their disease to hereditary causes. It has been well established that the majority of cancers are not genetically determined, but have a significant contribution to their expression from environmental toxins.

Resources:

Lipton, Bruce. Biology of Belief: Unleashing the Power of Consciousness, Matter and Miracles. (Mountain of Love, 2005), 67.

Lipton, Bruce. Biology of Belief: Unleashing the Power of Consciousness, Matter and Miracles. (Mountain of Love, 2005), 72.

Is Your Histamine Intolerance Actually Mast Cell Activation Syndrome?

Are you wondering if your histamine intolerance or allergic reactions are actually an issue with your mast cells? Or maybe you’ve experienced chronic symptoms that seem like allergies for as long as you can remember?

Histamine is an important but potentially dangerous mast cell mediator and part of the immune system response. Histamine is secreted by mast cells into surrounding connective tissues when there’s an exposure to an allergen. Mast cell histamine works by increasing the permeability of blood vessels and allowing white blood cells and proteins to access affected tissues more easily.

Histamine intolerance is a condition that’s growing in recognition. However, it is mostly considered a part of a much wider problem which is defined as Mast Cell Activation Syndrome (MCAS); a situation in which part of the innate immune system becomes hyperactive and releases multiple inflammatory mediators, of which histamine is one.

Histamine intolerance is considered to be present when there is just too much histamine in your body for it to cope. This is further exacerbated by the fact that histamine is also present in many foods and so a person’s histamine burden may be further amplified by their diet. This histamine isn’t broken down due to a DAO gut enzyme deficiency, or a HNMT deficiency in the liver. A comprehensive guide regarding the low-histamine diet can be found here.

Histamine intolerance is a subset of MCAS

Mast Cell Activation Syndrome is often confused for histamine intolerance. The difference between the two is that when a person has MCAS, their mast cells secrete many mediators, not just histamine. Though, histamine is still a major component of MCAS it’s only a piece of the puzzle.

Histamine intolerance is actually a subset of MCAS. If you’ve discovered you’re histamine intolerant or recently received a diagnosis, you should also be tested for MCAS.

Conditions associated with MCAS

Because MCAS is a multisystem condition with inflammation at it’s core, it’s been associated with a number of other conditions including:

  • Chronic inflammatory response syndrome (CIRS)
  • Irritable bowel syndrome
  • Gut dysbiosis – the gut is rich in mast cells and home to over 70% of the immune system. Parasites, bacteria, fungi, and parasites can all trigger gut mast cells.
  • Obesity
  • Diabetes
  • Asthma and allergies
  • Autoimmune diseases (such as lupus, rheumatoid arthritis, and Hashimoto’s)
  • Candida overgrowth
  • Celiac disease
  • Parasite infections
  • Skin conditions such as eczema and psoriasis
  • Food intolerances and allergies
  • Gastroesophageal reflux (GERD)
  • Infertility and endometriosis
  • Postural orthostatic hypotension (POTS)

If you’ve been diagnosed with one of these associated conditions, it could mean that being diagnosed with MCAS is more likely. Make an appointment with a doctor who specializes in MCAS and begin the diagnostic process. It can be somewhat of a journey, but once you know you have MCAS there’s a lot that can be done to relieve your symptoms and improve your life.

For a comprehensive guide on Mast Cell Activation Syndrome, you can read my in-depth article, Mast Cell Activation Syndrome and Mast Cell Histamine: When Your Immune System Runs Rampant.

[embed_popupally_pro popup_id=”5″]

Resources:

https://www.ncbi.nlm.nih.gov/pubmed/25773459

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507480/

https://www.ncbi.nlm.nih.gov/pubmed/15462834

Reversing Alzheimer’s and Preventing Cognitive Decline: Seven Steps You Can Take Today

Alzheimer’s disease is a devastating condition for both patients and their families. Unfortunately, Alzheimer’s disease (AD) is also on the rise globally. Effective treatment of AD has been of growing concern within the medical community because its prevalence continues to spread. The fact of the matter is that Alzheimer’s treatment demands a different approach.

While our treatments of many other chronic diseases ( heart disease, diabetes, cancer) have improved over the years, effective Alzheimer’s treatments continue to remain incomplete and disappointing.

Alzheimer’s disease not only impacts patients’ health, but it is physically, emotionally, and financially taxing on their families as well. It is estimated that AD will directly impact over 15% of the US population, meaning its indirect effect on families and caretakers is widespread and includes hundreds of millions of people.

Unfortunately, as a society, we have come to view cognitive decline, a precursor to Alzheimer’s disease, as an accepted sign of aging.

However, this is a myth that needs to be immediately dispelled. The types of cognitive decline associated with AD are NOT normal signs of aging.

Still, there is good news when it comes to Alzheimer’s disease. New methods have shown promise in completely stopping and even reversing cognitive decline in patients.

Let’s look more deeply into these methods and uncover ways you can help yourself or your loved ones who are suffering from this devastating disease.

Today, there is more hope than ever before for those touched by Alzheimer’s.

Alzheimer’s Reaches Epidemic Proportions

According to the World Alzheimer Report 2016, approximately 47 million people globally live with dementia, and estimates for 2050 are projected to be more than 131 million. In fact, Alzheimer’s disease (AD) is now considered the third leading cause of death in the United States, just behind cardiovascular disease and cancer.

Women are at the heart of this epidemic. About 65% of all those who develop AD are women, and 60% of all caretakers of those affected by AD are women. Women are now more likely to develop AD than breast cancer. Many believe this is because women live longer than men, but this reasoning still does not explain or justify why this condition is on the rise. Of significance is that only 5% of Alzheimer’s cases are familial, i.e., having a genetic basis that causes early onset Alzheimer’s. The rest are caused by lifestyle factors that are influenced by many variables over which patients have a significant degree of choice and control.

Nonetheless, the question remains: Why is Alzheimer’s worsening, and what can be changed in how we approach the treatment of such a deadly and heartbreaking disease?

Other treatments of chronic illnesses such as cardiovascular disease, HIV, and cancer have improved because of the combination therapies that have been applied, and yet a majority of AD treatment has been focused primarily on monotherapeutic drug treatments. It is a startling fact that neurodegenerative diseases have not benefitted as other diseases have from advances in modern medicine. Only through tackling a disease like Alzheimer’s with multiple therapies can we find a successful approach to reducing the growing global impact it is having on our society.

Research has found that AD involves extensive networks of molecular interactions, which means the disease demands a network-based, multi-system treatment approach. The key issue in understanding Alzheimer’s is that it is not a single disease; the different biochemical imbalances involved require different treatments. There is no single drug that will cure Alzheimer’s, and nor will there ever be one. Present Alzheimer’s drug treatments make only slight differences to symptoms but do little to address disease progression.

At the forefront of this functional medicine approach to AD is Dr. Dale Bredesen and his team from the Buck Institute for Research on Aging. Through careful examination of the pathogenesis of Alzheimer’s, Dr. Bredesen and his team have found promising results. They have developed a multiple modality approach to achieving what they call metabolic enhancement for neurodegeneration (MEND), now referred to as Reversal of Cognitive Decline or ReCODE.

Through the approach Dr. Bredesen has developed, patients have been able to dramatically improve cognitive function, achieve reversal of symptoms, and in some cases, return to work. The ReCODE program includes lifestyle interventions, therapeutic diets, and targeted nutrients.

Before we dive into Dr. Bredesen’s program, it is important that we understand the pathogenesis of AD and its six subtypes. Let’s take a closer look at this disease, how it presents itself, how it develops, and what can be done to prevent it.

The Development of Alzheimer’s

The reason a multifaceted approach is needed for the treatment of Alzheimer’s is because its cause is not due to any single factor. Many metabolic processes are at play. In fact, there are six different subtypes of AD, distinguished by the different metabolic abnormalities that underlie the root causes of each form of this condition.

An individual usually develops Alzheimer’s disease after the age of 65. Symptoms begin showing as general memory loss and eventually progress to further impact daily life. The 10 warning signs and symptoms of Alzheimer’s disease versus normal signs of aging are listed below.

Alzheimer’s disease Symptoms Signs of Normal Aging
Memory loss that disrupts daily life, especially forgetting newly learned information Forgetting newly learned information such as appointments or names but being able to recall them later
Having difficulty solving everyday problems such as paying billsMaking occasional errors but none that are significant or out of the ordinary
Struggling to complete familiar tasks such as driving home or to workNeeding help setting up new equipment or electronics
Losing track of dates, seasons, or timeTemporarily forgetting the day but having the ability to recall it later
Difficulty judging distance, spatial relationships, and contrastWorsening vision caused by cataracts
Trouble recalling words for things, following conversations, and speakingOccasionally having difficulty finding the preferred word while not forgetting names of items
Misplacing items and not being able to retrace stepsBeing able to remember steps to find misplaced items
Poor judgement or decision-making; inability to multitask Occasionally making poor decisions, but  rarely with major negative consequences
Social withdrawalPreferring to socialize a bit less
Changes in personality and moodBecoming irritated when things are not done a particular and preferred way.

Click here for an Alzheimer’s Questionnaire.

Signs and symptoms of AD are not normal signs of aging. If you or someone you love is experiencing any of these symptoms, it is important to make an appointment with your functional medicine doctor as soon as possible because AD worsens over time.

AD is a progressive disease and although there is no cure, Dr. Bredesen’s protocol has been able to slow and reverse cognitive decline. Remember, the earlier AD is caught, the easier it is to successfully treat the condition.

Once a person has noticeable symptoms, they are in the later stages of cognitive decline. AD has an initial “silent phase,” where brain degeneration is occurring but these changes are not detectable using objective tests. Patients may, however, notice slight memory and cognitive changes. See the image below.

Alzheimer’s disease (and dementia) does not begin suddenly.

Before AD develops, there is a noticeable slow decline in mental health. It has been estimated that the pathophysiology of the disease exists for approximately 20 years before any diagnosis is made. This means that many individuals have the beginnings of the disease without actually realizing it.

Preclinical begins with a subtle loss of neurons and a subjective sense of the brain’s mental processes not being as sharp as they once were.

Mild Cognitive Impairment is said to be present when a noticeable decline in mental functioning is noticed by others, and objective cognitive testing (performed simply by doing a mini-mental exam, computerized cognitive testing such as the CNS Vital Signs test, or a more sophisticated workup by a neuro-psychologist) is decreased. Activities of daily living have not yet been affected.

Dementia is said to occur when cognitive decline is sufficient to interfere with daily life. Objective testing such as PET scans and Neuroquant MRIs will show distinct patterns of brain changes such as cortical and hippocampal atrophy, reduced glucose uptake, and amyloid-beta-production.

Temporal Progression of Cognitive Impairment

What exactly is Alzheimer’s disease?

Simply put, Alzheimer’s has been observed to occur when the genes associated with the disease cause brain cells to become suicidal. The question that Dr. Bredesen asked was, “What are the fundamental processes and mechanisms that drive these genes to turn on and cause brain cells to die?”

Based on numerous studies, we now know that AD results from an imbalance in the destruction of neurons and synapses and the building up and maintenance of synapses and neurons. It has been observed that a molecule known as amyloid-beta accumulates in higher than normal concentrations in the brain, which causes the synapses, along with the neurons essential for memory, to die.

Where does amyloid-beta come from? It is derived from the amyloid precursor protein (APP), of which amyloid-beta is but a small portion. The APP, once produced by neurons, is cut by molecular scissors called proteases, which can cut at any of the three spots along the APP or at one distinct site. If the APP is cut at three particular sites, the four peptides produced from this action underlie the process of the synaptic loss and neuronal death that characterize AD. If, however, the APP is cut at just a single site, the two peptides that result cause just the opposite to occur; synaptic connections are maintained and neuron growth is nourished. These two peptides are referred to as the anti-Alzheimer’s peptides. See image below.

Alternative processing of, and signaling by, APP

Thus, the APP appears to act as a molecular switch that mediates plasticity-related processes. In summary, in order to reduce your risk of AD, you have to maintain all the necessary lifestyle practices and therapies that induce the two brain-affirming, anti-AD peptides and reduce all the factors that induce the production of the four pro-AD-inducing peptides. How exactly to achieve this, forms the basis of Dr. Bredesen’s ReCODE program.

AD is similar to other chronic illnesses in that there is an age-associated imbalance between the building up of cells that mediate neural plasticity and the destruction of cells. In AD, this occurs at the level of neuronal synapses, called synaptoblastic (building up of synapses), as opposed to synaptoclastic (destruction of synapses) activity. These intricate processes happen over time, in reinforcing cycles.

Six Subtypes of Alzheimer’s disease

Understanding the different Alzheimer’s subtypes is also critical for creating the best treatment plan for each patient.

There are numerous metabolic processes involved in contributing to AD, with six different subtypes that have been identified by Dr. Bredesen. These six subtypes are based on three papers by Dr. Bredesen: The first paper, in 2014, describes the initial contributions to his protocol (first called MEND), the second paper in 2016 outlines 10 case studies, and the third paper, also in 2016, describes neurodegeneration due to biotoxin exposure.

These subtypes are not widely used in diagnostic workups and clinical protocols at this time, but understanding the differences is essential to creating a comprehensive treatment plan. The six subtypes of Alzheimer’s disease are as follows:

Subtype 1 (inflammatory or “hot”) Alzheimer’s: Patients with this form of AD have predominantly inflammatory symptoms. These proinflammatory factors include cytokines, chemokines, acute-phase reactants, and other inflammation-causing mediators.

Patients with subtype 1 AD also have increased levels of c-reactive protein, high interleukin-6, and a low albumin-to-globulin ratio. The microglia and activated astroglia (brain structures) are also inflamed.

There is also an antagonism between the sirtuinT1 enzyme (anti-inflammatory) and NFkB (the nuclear factor k-light-chain enhancer of activated B cells [proinflammatory]); when NFkB inflammation is activated and SirT1 is suppressed, it can alter gene transcription and turn on gamma-secretase and beta-secretase. Gamma-secretase cleaves to the APP and contributes to synaptoclastic destructive processes within the brain.

The inflammation in subtype 1 primarily involves the innate immune system, and usually (but not always), there is systemic inflammation. Onset of this subtype typically occurs in an individual’s 70s or later.

Subtype 1.5 (glycotoxic or “sweet”) Alzheimer’s: This subtype is the in-between of subtypes 1 and 2 because it involves both inflammatory perpetrators and atrophic processes. Glucose regulation is impaired, resulting in insulin resistance and inflammation due to hyperglycemia (increased blood glucose). This glucose dysfunction also disrupts hormone-signaling and trophic factors (molecules that allow neurons to maintain and create neighboring connections).

Subtype 2 (atrophic, non-inflammatory, or “cold”) Alzheimer’s: Patients with subtype 2 AD have atrophic symptoms, meaning there is degeneration and dysfunction of neurological functions due to the insufficiency of certain nutritional and metabolic factors. Even though this underlying cause is different from inflammation, it still results in the same disease.

Similar to subtype 1, subtype 2 causes the APP to create amyloid plaques. Subtype 2 AD is associated with declining trophic factors, such as nerve growth, brain-derived neurotrophic factors (BDNF), testosterone, estradiol, vitamin D, thyroid hormone function, and insulin levels.

All of these declining trophic factors cause your brain to stop synaptogenesis (creation of new synapses), which is why learning new things becomes more difficult and worsens over time.

Subtype 3 (toxic or “vile”) Alzheimer’s: Subtype 3 is caused by toxin exposures, most commonly inhaled toxins (such as mold mycotoxins), and is sometimes called inhalational Alzheimer’s disease (IAD). One 2014 study showed fungal proteins in the brains of Alzheimer’s patients, and another study in 2015 showed fungal infections in the brains of Alzheimer’s patients. Fungal DNA and proteins were detected in the brain tissue from AD patients, but not in controls. Fungal particles could also be detected in the neurons of the same AD patients. Herpes simplex type 1 (HSV-1) and chlamydia pneumoniae have also been associated with amyloid protein production in AD.

Many patients with subtype 3 AD have markers of chronic inflammatory response syndrome (CIRS) but do not fit the official criteria for a CIRS diagnosis. Dr. Bredesen says that those with IAD will have lab results similar to those of CIRS patients, but their symptoms are mostly Alzheimer’s-like dementia.

Typically, patients with this form of AD have high levels of the complement component C4a and the transforming growth factor beta-1 (TGF-b1), both of which are specific inflammatory cytokines, as well as high levels of matrix metallopeptidase 9 (MMP9), an enzyme involved in the cell membrane penetration of inflammation. Patients also have decreased levels of the melanocyte-stimulating hormone (MSH), the vascular endothelial growth factor (VEGF), and the antidiuretic hormone (ADH). Usually, there are other abnormalities present such as high levels of cortisol and low levels of the adrenocorticotropic hormone (ACTH) and the antidiuretic hormone (ADH).

Symptoms of subtype 3 AD are similar to those of the other subtypes in that they include memory loss and difficulty with word recall; however, patients may also report having a metallic taste in their mouth and an increased sensitivity to smell. These patients rarely have the respiratory complaints, chronic fatigue, muscle pain, or other symptoms usually associated with CIRS.

Subtype 4 (vascular) Alzheimer’s: Alzheimer’s development in subtype 4 patients is a protective response to vascular insufficiency and results in a triggered amyloid response.

Subtype 5 (traumatic) Alzheimer’s: This subtype is characterized by head trauma, and these patients typically have significant personality changes. Not all head trauma patients will develop AD. One major study showed an 2.3 times increased risk of developing AD in older adults with a history of moderate traumatic brain injury than seniors with no history of head injury. Those with a history of severe traumatic brain injury had a 4.5 times greater risk of developing AD. Traumatic brain injury changes brain chemistry by inducing beta-amyloid and tau proteins, the hallmark proteins linked to AD. Traumatic brain injury may be more likely to cause dementia in individuals who have either one or two of the APOE-e4 genes. There are no studies linking mild brain injury or concussion to the development of AD.

Genetics and Alzheimer’s Disease

It is important to note subtypes 1, 1.5, and 2 are all associated with the ApoE4 gene mutation. Although 95% of all Alzheimer’s cases are not caused by genetics, genetic testing is essential to determine if there is a propensity for these forms of Alzheimer’s. In fact, what is called familial Alzheimer’s is very rare, appears to be clustered in families, and presents earlier in life. That said, two-thirds of AD patients carry one or two copies of the ApoE4 gene.

Individuals who are ApoE4-positive with one copy of the gene (approximately 75 million Americans) have a 30% lifetime risk of developing AD. Those with two copies of the gene (approximately 7 million Americans) face a 50% lifetime risk of developing AD.

Interestingly, scientists have found that while the ApoE4 gene increases the risk of subtypes 1 and 2, it decreases a person’s risk for developing subtype 3. This is believed to be due to the protective nature of ApoE4, which can fight off the microbes that cause subtype 3 AD. Ultimately, ApoE4 is thought to be an advantage in your youth but can contribute to chronic illnesses as you age.

You can be tested for ApoE4 with your functional medicine doctor. This is a good idea because if you have the ApoE4 gene mutation, there are certain measures you can take to decrease the chances of developing Alzheimer’s. The website www.apoE4.info is an excellent resource for individuals with one or two copies of this gene.

One fascinating behavior a person with the ApoE4 gene can implement in order to favorably influence the outcome is 12-hour fasting. The ApoE4 gene helps you survive famine, and so it makes sense that intermittent fasting can help those with the gene avoid Alzheimer’s. The ApoE4 allows your body to use fat more efficiently and go longer without eating. This means if you find out through testing you have this gene, fasting can be used as a tool to have your body switch to burning ketones for energy over glucose, which is believed to aid in preventing AD.

Even if you do have the APoE4 gene, you can still prevent Alzheimer’s disease from developing, but you have to be proactive, educate yourself, and implement as many of the lifestyle factors as you possibly can. Let’s look at how to do that.

What Do All Forms of Alzheimer’s Disease Have in Common?

There are 36 mechanisms that Dr. Bredesen has identified as contributing to Alzheimer’s, but mitochondrial dysfunction is at the core of all of these.

Your mitochondria are the powerhouses of your cells, creating the energy molecules (ATP) every cell of your body needs to function. Additionally, free radicals (damaging molecules produced as byproducts of normal metabolism but enhanced by toxic exposures, genetic detoxification, and nutritional deficiencies) tend to be created in your mitochondria. When you have a higher incidence of free radicals in your cells, your mitochondria suffer damage and cannot produce adequate amounts of ATP, resulting particularly in neuronal cell death.

Through his research, Dr. Bredesen found that the APP makes amyloid in response to your cells being under attack by free radicals and toxic substances. Your body’s trophic support may also be decreased. Together, both low trophic factors and increased amyloid levels contribute to cognitive decline.

The complexity behind the pathogenesis of Alzheimer’s disease is why a comprehensive, multivariable approach is necessary. With that in mind, Dr. Bredesen’s recommendations include addressing these 36 mechanisms:

  • Increasing mitochondrial function; mitochondria produce ATP, the necessary chemical responsible for the energy needed for nerve growth, health, and maintenance.
  • Increasing mitochondrial protection
  • Decreasing beta-amyloid production, the main component of amyloid plaques found in Alzheimer’s
  • Increasing beta-amyloid degradation
  • Decreasing beta-amyloid oligomerization, i.e., the creation of longer molecules of beta-amyloid
  • Increasing the brain-derived nerve factor (BDNF), a neuropeptide with growth effects on neurons
  • Increasing the nerve-growth factor (NGF), a neuropeptide involved in the growth and maintenance of neurons
  • Increasing the granulocyte-stimulating factor (G-CSF), a growth factor that has neuroprotective effects and that increases neuronal growth
  • Increasing the activity-dependent neuroprotective protein (ADNP), a protein essential to brain health and cognitive function
  • Decreasing p-tau; neurofibrillary tangles are aggregates of hyperphosphorylated tau proteins, which are primary markers of Alzheimer’s disease.
  • Decreasing homocysteine, a proinflammatory protein
  • Building synapses
  • Increasing beta-amyloid breakdown
  • Increasing the albumin/globulin (A/G) ratio, indicative of inflammatory AD
  • Decreasing inflammation
  • Inhibiting NF-kB, a protein complex that controls inflammatory cytokines
  • Increasing glutathione (GSH), a major antioxidant
  • Increasing antioxidants, which decrease neuroinflammation
  • Decreasing iron, a pro-inflammatory mineral
  • Increasing cerebral blood flow
  • Increasing acetylcholine, a neurotransmitter involved in memory
  • Increasing alpha-seven nicotinic acetylcholine receptors (α7), a critical link between neurodegeneration and AD
  • Increasing amyloid-beta transport
  • Increasing amyloid beta clearance
  • Decreasing the ApoE4 effect; this gene determines increased risk for AD, with the 4/4 gene having the highest risk
  • Increasing gamma-aminobutyric acid (GABA), a calming and neuroprotective neurotransmitter that downregulates glutamate, an excitatory neurotransmitter
  • Decreasing N-methyl-D-aspartate receptor activity (NMDA), a receptor that regulates the activity of glutamate, an important neurotransmitter in the brain involved in learning and memory
  • Optimizing hormones, especially estradiol, progesterone, testosterone, DHEA, and thyroid
  • Increasing vitamin D
  • Decreasing the pro-form of the neuron growth factor (pro-NGF), a protein expressed at higher levels in brains of AD patients
  • Decreasing caspase-6, the activity of which is associated with increased risk of AD
  • Decreasing the N-terminal fragment of the beta-amyloid precursor protein (N-APP)
  • Enhance detoxification
  • Increasing vascularization
  • Increase telomere length
  • Reduce toxic metals

Dr. Bredesen explains that these are like holes in a roof, which need to be individually addressed in order for a full recovery to be made.

It is important to realize that AD is a protective response to three major metabolic and toxic disturbances:

  1. Inflammation- be it infectious (viruses) or sterile (modified inflammatory proteins)
  2. The withdrawal of trophic support (e.g. nerve growth factor, estradiol, testosterone, vitamin D etc.)
  3. Exposure to toxins such as mercury, aluminum, mold mycotoxins.

Dr. Bredesen has identified a number of factors that induce the APP receptor to go in the right direction of trophic or building synapses and neuronal health. The APP responds to dozens of molecules that assist brain health and anti-Alzheimer’s protection. Our brains have 100 billion neurons, and each neuron has approximately 10,000 connections, called synapses. Synapses are critical for cognitive functioning, memory storage, decision-making, and neurotransmitter communication. One’s brain has nearly one quadrillion energy-demanding synapses to power and run efficiently with energy-producing raw materials. In short, the APP has to constantly assess if the incoming data is shifting the lever in the direction of neuronal building or in the direction of neuronal destruction.

The sum total of the way one lives one’s life minute-to-minute affects this highly complex algorithm shift in either one of two directions—towards brain protection and maintenance, or towards brain inflammation, destruction, and reduced neuronal death. It really does come down to choice. AD begins with the loss of function of the synapses, the loss of the synapses themselves, and eventually, the loss of brain cells themselves, leading to brain shrinkage that is visible on MRI scans.

When one is young, the ratio between neuronal growth and destruction is equally balanced between the two. As we age, the destructive (clastic) part of the process tends to dominate over the building (blastic) part of brain preservation. We must decide to do all we can do to downregulate any of the factors that induce inflammation and further clastic activity and upregulate anything we can that induces growth, blastic activity, and hence, neuronal plasticity.

The realization that multiple factors induce brain growth as well as brain destruction will explain why the single drug model of AD treatment has not borne any fruit. There is no single drug that can ever address the complexity of all the metabolic factors that contribute to brain health maintenance and optimization. Dr. Bredesen’s analogy is that of a roof with 36 holes in it. A roofer called in to fix only one hole where the rain is pouring in will never be able to stem the flood of water pouring in through the other 35 holes no matter how well he patches the one hole.

Robert M Cardiff, MD, Commissioner of the Food and Drugs Administration (FDA) concurs with this observation:

“Multimodal therapy approaches that combine interventions aimed at different aspects of disease are emerging as potential-and perhaps essential-ways to enhance clinical outcomes for patients with psychiatric and neurological disorders. Indeed, for most chronic diseases, multiple pathways are involved simultaneously, making it unlikely that a single treatment will prove sufficiently effective.”

From these insights it is important to realize that we do not get Alzheimer’s for no reason. There are many possible reasons and the doctors of the future will be trained to investigate and look for many if not most of these factors identified to date.

Dr. Bredesen’s ReCODE program aims to achieve the following:

  1. Optimize metabolic parameters to the maximum, not just simply normalize them.
  2. Address as many of the causative network components as necessary with the understanding that combination effects will be additive and cumulative and will create an effect that is more than the sum of the many single therapies.
  3. The more that patients are able to achieve in terms of their therapeutic input, the more likely it is that a certain threshold will be reached that will tip them over from a pathogenic process to a therapeutic benefit. This implies that a combination of therapies will be more than the sum of individual parts.
  4. A personalized approach is needed with a prioritization of therapeutic inputs, which needs to be computerized and analyzed according to the laboratory values affecting the plasticity networks.
  5. Repetitive application of therapeutics is necessary to optimize outcomes over time.
  6. The goal of therapy is to use a physiological approach with as much of an upstream causative approach that can possibly be implemented.

A Therapeutic System was developed by Dr. Bredesen

Therapeutic System (adapted from Bredesen, 2014 and cited by Ash, 2015)

The critical role of several factors in Alzheimer’s disease necessitates several therapeutic interventions. The required interventions seek to:

  • reduce inflammation
  • address autoimmunity
  • minimize insulin resistance
  • decrease amyloid-beta (Aβ)
  • reduce excess cortisol and the corticotropin-releasing factor (CRF).

In so doing:

  • the hypothalamic adrenal axis is supported
  • antioxidant function is optimized
  • blood glucose is balanced
  • acetylcholine synthesis is supported.

Interventions identified by Bredesen (2014) to achieve these aims include:

  • Diet optimization to minimize simple CHO, inflammation, and insulin resistance: Simple CHO, inflammation, and insulin resistance are minimized by providing patients with a choice of several low-glycemic, low-inflammatory, and low-grain diets.
  • Autophagy and ketogenesis enhancement: Autophagy and ketogenesis are enhanced by having the patient fast for 12 hours each night (including at least three hours before bedtime), thereby reducing insulin and Aβ levels.
  • Stress reduction: Stress is reduced by having the patient engage in personalized stress reduction activities (e.g., yoga, meditation, music, etc.) that target the stress axis, reduce cortisol, and equilibrate the CRF.
  • Sleep optimization: Sleep is optimized by having the patient follow a sleep regimen, including eight hours of sleep per night, the use of 0.5 mg melatonin and/or 500 mg of tryptophan if awakening, in addition to ruling out possible sleep apnea.
  • Exercise regimen: Patients are provided with an exercise regimen, including 30–60 minutes of physical exercise 4–6 days per week.
  • Brain training and stimulation: Patients are provided with BrainHQ or related brain-training software programs.
  • Homocysteine optimization: Homocysteine is optimized to <7 using methylcobalamin (Me-B12), methylfolate (MTHF), pyridoxal-5-phosphate (P5P), and, if necessary, trimethylglycine (TMG). Optimization of serum B12: Serum B12 is optimized to >500 using methylcobalamin (Me-B12).
  • Lowering c-reactive protein: Due to the critical role of inflammation in Alzheimer’s disease, c-reactive protein is lowered to <1 through the use of optimized hygiene and an anti-inflammatory diet that includes curcumin and fish oil (DHA/EPA).
  • Insulin optimization: Due to the role of inflammation in Alzheimer’s disease and the relationship it shares with type II diabetes, insulin levels are optimized to <7 (fasting) and hemoglobin A1c (HbA1c) to <5.5 through the use of an anti-inflammatory diet.
  • Hormone optimization: Hormones are optimized, including free T3, free T4, the thyroid-stimulating hormone (TSH), pregnenolone, progesterone, estradiol, testosterone, cortisol, and dehydroepiandrostenedione (DHEA).
  • Restoration and optimization of gastrointestinal health: Gastrointestinal health is restored, repaired, and optimized, including the use of prebiotics, probiotics, and avoidance of inflammation and autoimmunity.
  • Reduction of a-beta Levels: A-beta (Aβ) levels are reduced using curcumin and ashwagandha (an Ayurvedic adaptogenic herb).
  • Cognitive enhancement: Cognitive enhancement is achieved through the use of bacopa monniera (an Ayurvedic herb known for its cognitive enhancing properties) and magnesium threonate (MgT).
  • Optimization of vitamin D3: Vitamin D3 (25-OH-D3) levels are optimized to 50–100 ng/ml (US levels), using vitamins D3 and K2.
  • Nerve-growth factor optimization: The nerve-growth factor is increased using h. erinaceus or acetyl-l-carnitine.
  • Provision of synaptic structural components: Provide synaptic structural components using citicoline and docosahexaenoic acid (DHA).
  • Optimization of antioxidants: Optimize antioxidants using mixed tocopherols and tocotrienols, selenium (Se), blueberries, n-acetyl-cysteine (NAC), ascorbate, and a-lipoic acid.
  • Optimization of the zinc:copper (zn:cu) ratio: Optimize the zn:cu ratio based on values obtained.
  • Ensure nocturnal oxygenation: Ensure nocturnal oxygenation through treating or ruling out sleep apnea.
  • Optimize mitochondrial function: Optimize mitochondrial function through optimizing CoQ or ubiquinol, a-lipoic acid, pyrroloquinoline quinone (PQQ), n-acetylcysteine (NAC), N-acetyl-L-carnitine (ALCAR), selenium (Se), zinc (Zn), resveratrol, ascorbate, and thiamine.
  • Increase focus: Increase focus using pantothenic acid as required for acetylcholine synthesis.
  • Increase SirT1 function: Increase SirT1 function using resveratrol.
  • Exclude heavy metal toxicity: Evaluate mercury (Hg), lead (Pb), and cadmium (Cd) to confirm or exclude heavy metal toxicity; chelate if indicated to address the effects of heavy metals on the central nervous system.
  • Increase medium-chain triglyceride (MCT) oil effects: Use coconut oil or Axona.

According to Dr. Bredesen’s research and discussions, the effects of various targeted therapies may be additive, multiplicative, accumulative, and synergistic.

A functional medicine approach is the most effective way to implement these approaches.

7 Things You Can Do to Prevent Cognitive Decline Right Now

Here are some things you can do right now to work on your own personal cognitive health, using similar principles to those found in the Bredesen ReCODE Protocol.

1. You Must Get Quality Sleep

Getting seven to eight hours of quality sleep each night is critical to promoting cognitive function because during sleep is when your body removes metabolic waste from your body.

If you have sleep apnea, you must address it. Your brain is starved of oxygen when you have sleep apnea, and it directly impacts your cognitive abilities. Ask your doctor to refer you for a sleep study.

2. Implement Overnight Fasts

By putting your body in an overnight fast (12 hours at least), you induce ketogenesis (you also need a low-sugar and low-carb intake to promote this). When your body is in ketogenesis, your insulin levels are lowered. Additionally, amyloid-beta levels are reduced, which are a main contributor to the amyloid plaques found in Alzheimer’s patients. A low-sugar and low-carb diet makes overnight fasting surprisingly easy.

3. Reduce Carb and Sugar Intake

Diets with few carbs and little to no sugars are the best for reducing inflammation in the body, and they reduce your chances of developing insulin resistance. Additionally, low-sugar and low-carb diets have been linked to a decreased risk of developing Alzheimer’s disease.

4. Reduce Your Toxic Load

Reducing toxin exposure gives every bodily system a better chance at functioning properly, and your mitochondria and metabolic systems are no exception.

You can reduce your toxic load through having good air and water filters in your home. Additionally, avoid toxin-containing items such as:

  • Non-stick and aluminum pans
  • Harmful personal care products (you can check your items against the EWG Database)
  • Harsh cleaning products (opt for natural solutions)
  • Paints with volatile organic compounds (VOCs)
  • Metal dental fillings
  • Fish high in heavy metals
  • Plastics with BPA
  • Charred and fried meat (high-lipid peroxidation)

Remember, if your lab results are coming back similar to those of a CIRS patient, yet you are not having typical symptoms of CIRS, check for signs of Alzheimer’s and other indicators of toxin exposure due to building damage from mold and water (inflammagen exposures).

5. Add These Supplements

Dietary changes are at the heart of the Bredesen Protocol, and by adding certain supplements, you can protect your brain. Consider the following supplements because each has shown to promote healthy brain function.

  • Vitamin B12—methylcobalamin
  • Vitamin C – must be taken twice daily as it is water soluble and is excreted quickly
  • Vitamin E—mixed tocopherols
  • Turmeric—a lipophilic form is best
  • Vitamin D—measure your 25 OH Vitamin D levels to achieve the optimal dosage for you
  • DHA (found in fish and fish oil supplements)
  • Citicoline
  • Probiotics

6. Exercise Every Day

Having an exercise routine has been unequivocally linked to a reduction in cognitive decline. Studies have found that even a walk each day significantly slows the decline of Alzheimer patients.

I encourage you to get up and move at least once a day. Even a quick 15-minute high-intensity interval workout has been shown to be as effective as an hour-long workout.

7. Reduce Stress

Stress causes high levels of cortisol and CRF, which are both linked to Alzheimer’s. Add stress-reducing habits to your day. These can include quick meditations, yoga, listening to calming music, or taking walks.

Reversing Cognitive Decline Is Within Reach

We are living in an exciting time when it comes to Alzheimer’s treatments. Through a comprehensive approach to this illness, we may be able to slow down and even reverse most cases of Alzheimer’s.

While the Bredesen Protocol works to reverse cognitive decline, we can take the same science and apply it to our lives today to prevent Alzheimer’s from developing in the first place. We can even take these concepts one step further and optimize brain health to improve function overall.

Share this article with someone you know who would benefit from hearing about this monumental approach to a devastating disease. The future of Alzheimer’s treatment is bright.

[embed_popupally_pro popup_id=”5″]

Resources:

The End of Alzheimer’s. Dale Bredesen  Avery – An Imprint of Penguin Random House 375 Hudson Street New York, New York 10014, 2017

https://www.alz.co.uk/research/WorldAlzheimerReport2016.pdf
https://www.ncbi.nlm.nih.gov/pubmed/24598707
http://www.alz.org/shriverreport/shriver.html
https://www.alz.org/downloads/facts_figures_2014.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221920/
https://www.drbredesen.com/thebredesenprotocol
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931830/
https://www.ncbi.nlm.nih.gov/pubmed/23703924
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586104/
https://www.integrativepractitioner.com/whats-new/news-and-commentary/six-types-of-alzheimers-disease-and-how-to-identify-them/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198708/
http://www.alz.org/10-signs-symptoms-alzheimers-dementia.asp
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789584/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779441/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367001/
http://www.ewg.org/skindeep/
https://hoffmancentre.com/2017/08/exercise-smarter-not-harder-optimize-workout-brain-body/
https://docs.wixstatic.com/ugd/1a2e49_f479c410646548dc9d5a20ef26dc3b8c.pdf
https://docs.wixstatic.com/ugd/1a2e49_a6311e25b2e844c2986b03143356f415.pdf
https://docs.wixstatic.com/ugd/1a2e49_51f1e35c438e4d8c9a49fccc6e9efd18.pdf

12 Tips for Living With Mast Cell Activation Syndrome

Living with Mast Cell Activation Syndrome (MCAS) usually results in widespread mast cell activation syndrome symptoms that are seemingly unrelated. Unfortunately, most people go many years or even their whole life without a diagnosis.

If you’ve been diagnosed with MCAS or suspect you have this condition, the best course of action is making a series of lifestyle changes and working with your functional medicine doctor. Fortunately, many of the changes are easy to implement and you’ll see the benefits from implementing them fairly quickly.

Try not to get overwhelmed by this list, instead pick one or two items and incorporate them into your routine. Add a few items week by week, and soon enough you’ll have a comprehensive plan that has the potential to significantly improve your symptoms and your quality of life.

1. Adopt a low histamine diet

Avoid leftover foods, alcohol, cured meats, canned fish, pickled and fermented foods, berries, citrus, nuts, chocolate, dairy, yeast, soy sauce, tomatoes, vinegar, and preservatives. A comprehensive guide to a low histamine diet can be found here.

2. Avoid triggers of MCAS (non-food items)

Avoid temperature extremes, mold, emotional stress, insect bites, chemicals in personal products, medications that liberate histamine of block DAO, sodium benzoate (common food preservative), airborne chemicals, smoke, heavy metals and anesthetics.

3. Work on your gut health

Good gut health is a cornerstone of overall wellness and will help you get your MCAS under control. Cut back on food that damages the gut or causes inflammation. Take probiotics and a DAO enzyme (generic name Umbrellux DAO).

4. Stabilize mast cell mediator release

Stabilize mast cell release of histamine with quercetin and vitamin C.

5. Use H1 and H2 blockers every 12 hours

Try using 5 mg of levocetirizine twice daily and 20 mg of famotidine twice daily.

6. Block and reduce nighttime histamine release

You can block nighttime histamine release and get a better night’s sleep by taking 0.25 -1 mg of ketotifen or zaditen at night.

7. Treat existing infections

Treat any existing infections to help your body heal and reduce mast cell triggers. Get a thorough examination with your functional medicine doctor and test for any pathogens.

8. Identify and remove toxins and allergens

When you have MCAS, you’ll do your body a world of good by reducing its toxin burden. You can reduce your exposure to toxins in your daily life through cleaning up your personal care products and opting for natural solutions, using natural household cleaners, and removing mercury fillings.

9. Take helpful nutrients

Support your health with important nutrients that assist in treatment. Some of these include vitamin B6, alpha lipoic acid, vitamin C, selenium, omega-3s, N-acetylcysteine, methyl-folate, SAMe, and riboflavin.

10. Add supportive herbs

Take nigella sativa, butterbur, turmeric, ginger, and peppermint to support your MCAS treatment.

11. Get into a routine and stick to it

Try to stick to a routine because your body’s cycles are closely linked to your daily activities. This will also help you get high quality sleep, which is essential to reducing the impact of MCAS on your life.

12. Reduce stress

Stress can activate your mast cells and cause them to release mediators like histamine. Reducing stress is important for anyone living with MCAS.

For a comprehensive guide on Mast Cell Activation Syndrome, you can read my in-depth article, Mast Cell Activation Syndrome and Histamine: When Your Immune System Runs Rampant.

Mast Cell Activation Syndrome Diet

Another great resource for dealing with histamine and MCAS using a mast cell activation syndrome diet and exercise is through Yasmina Ykelestam at Healing Histamine.

[embed_popupally_pro popup_id=”5″]

How to Tell If You Have Mast Cell Activation Syndrome

If you’ve been searching for solutions to your mysterious health symptoms, they could be caused by Mast Cell Activation Syndrome.

Mast cell activation syndrome (MCAS) is an immunological condition where mast cells inappropriately secrete mast cell mediators. Mediators include but are not limited to histamine, which can cause widespread and chronic inflammation.

This mediator release can be excessive and/or chronic and result in long-lasting symptoms in almost any cell of the body where their receptors are found. This can potentially affect every organ system in the body.

Some experts believe as many as 14 to 17 percent of the US population have MCAS, which is one out of every six to seven people. It’s also been estimated to take up to 10 years to reach a mast cell activation syndrome diagnosis. This is mostly due to the lack of awareness surrounding MCAS.

Because mast cell activation syndrome goes unnoticed for years, I’d like to dig a bit deeper and uncover some of the symptoms and lab work available that can help with MCAS diagnosis.

Symptoms of MCAS

Patients who have MCAS typically have been struggling with inflammation-related symptoms over the years, which commonly include:

  • Having allergies as a toddler
  • Various rashes that came and went
  • Gut conditions (that may have been misdiagnosed)
  • Anxiety
  • Headaches
  • Insomnia
  • Poor wound healing

While these are common MCAS symptoms due to mast cell mediators occurring throughout the body, a person can be affected by symptoms that are more widespread. These can include, but are not limited to the following questions:

  • Feeling as though you’ve always been sick
  • Overreaction to bee stings and mosquito bites
  • Shortness of breath
  • Feeling lightheaded when you stand
  • Insomnia
  • Ringing of the ears
  • Facial and chest flushing
  • Frequent colds, infections or fevers
  • Food, chemical, and drug sensitivities and intolerances
  • Heat intolerance

You can also find a comprehensive list of MCAS symptoms in my in-depth article, Mast Cell Activation Syndrome and Histamine: When Your Immune System Runs Rampant.

You have the option to get testing done with a doctor to help confirm the MCAS diagnosis. I recommend you have these tests done with a doctor who’s experienced in MCAS because it’s still largely unknown, even in the medical community.

Lab work for MCAS

Working with a doctor who specializes in MCAS is your best bet as you’ll need to get testing on multiple occasions since the symptoms of MCAS wax and wane. False negatives are a common occurrence with MCAS testing. In fact, positive lab work is only obtained 20 percent of the time. However, testing can still give you a lot of valuable information regarding your mast cell mediator status. Testing for MCAS is quite complex and requires specialized handling of tissue samples.

The most important MCAS tests are:

  • Histamine – plasma – Quest 36586 – must be chilled. Normal range – 28-51 ug/l.
  • N-Methylhistamine – 24-hour urine – must be chilled. Normal range – less than 200 mcg/g.
  • Prostaglandin D2 – plasma – must be immediately chilled and spun in a refrigerated centrifuge. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  • Prostaglandin D2 (PGD2) – 24-hour urine – specimen collection must be chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  • Chromogranin A – Quest 16379 – must be off proton pump inhibitors (PPIs) and H2 blockers (Pepcid and Zantac) for 5 days before tests, since they can falsely elevate chromogranin A.

There are others you can have taken, which you can find in more detail in my in-depth article, Mast Cell Activation Syndrome and Histamine: When Your Immune System Runs Rampant.

More information regarding a low-histamine diet may found found in my guide here.

[embed_popupally_pro popup_id=”5″]

Resources:

20 Triggers of Mast Cell Activation Syndrome

In an effort to help you notice common triggers, below are 10 non-food and 10 food triggers that commonly provoke mediator release in those with MCAS.

10 Non-Food Triggers of Mast Cell Activation Syndrome

If you’re struggling or suspect you have MCAS, it’s in your best interest to reduce your exposure to these triggers, including:

  1. Extreme temperatures – either hot or cold
  2. Exposure to mold or Lyme disease and co-infections
  3. Emotional stress
  4. Insect bites
  5. Chemicals in personal products
  6. Medications that liberate histamine or block DAO
  7. Sodium benzoate –a common food preservative
  8. Airborne smells from chemicals or smoke
  9. Heavy metal toxicity – aluminum, mercury, lead, cadmium, bismuth and arsenic are known to be mast cell destabilizers
  10. Anesthetics

10 High Histamine Foods that Should be Avoided

Studies have shown that eliminating foods high in histamine and other triggers can significantly improve symptoms. Ten of the highest histamine foods include:

  1. Yeast and alcohol
  2. Dairy (especially fermented dairy like kefir)
  3. Gluten
  4. Fermented foods, especially sauerkraut, kombucha, miso
  5. Cured and smoked meats and fish
  6. Shellfish
  7. Citrus foods – lemon, lime, orange
  8. Vinegar
  9. Leftover and aged food – especially if left in the refrigerator and not frozen immediately
  10. Berries – strawberries, blueberries, raspberries

More information about histamine containing foods and following a low-histamine diet can be found here.

Conditions Associated with Mast Cell Activation Syndrome

Because MCAS is a chronic, multi-system, multi-symptom condition with an inflammatory theme, it’s been associated with a number of conditions and diseases, including:

  • Chronic inflammatory response syndrome
  • Irritable bowel syndrome
  • Gut dysbiosis – the gut is rich in mast cells and home to over 70% of the immune system. Parasites, bacteria, fungi, and parasites can all trigger gut mast cells.
  • Obesity
  • Diabetes
  • Asthma and allergies
  • Autism
  • Autoimmune diseases (such as lupus, rheumatoid arthritis, and Hashimoto’s)
  • Candida overgrowth
  • Celiac disease
  • Parasite infections
  • Skin conditions such as eczema and psoriasis
  • Food intolerances and allergies
  • Gastroesophageal reflux (GERD)
  • Infertility and endometriosis
  • Chemical and medication sensitivities
  • Postural orthostatic hypotension (POTS)
  • CIRS – exposure to mold mycotoxins is a potent stimulator of mast cell activation
  • Migraines
  • Depression
  • Fibromyalgia
  • Fungal infections
  • Tinnitus
  • Multiple Sclerosis
  • Cancer

In general, inflammation accompanies MCAS and most of its coinciding or associated illnesses. If you are struggling to get one of these illnesses under control, there’s a possibility MCAS could be causing further complications.

It’s a good idea to check for MCAS if you have any of the above conditions and vice versa.

[embed_popupally_pro popup_id="5"]

Mast Cell Activation Syndrome and Histamine: When Your Immune System Runs Rampant

There is undoubtedly an escalating epidemic of chronically unwell people in North America. The present method of looking at illness is geared toward a single organ, a single specialty, a single drug, and voila! – let’s hope for a cure. Often patients go from pillar to post to see various medical consultants according to specialty (gastroenterologists, dermatologists, etc.), only to discover there isn’t one underlying syndrome or root cause that explains all the assorted symptoms the patient is experiencing. Patients may be given multiple diagnoses with multiple treatment options or medications, often with conflicting interactions and side effects that are worse than the underlying condition they are meant to treat.

Recently, a number of new ways of looking at chronic multisystem, multisymptom diseases has emerged as pioneering physicians connect previously disconnected dots and make sense of disparate symptoms that were never understood as components of a single syndrome. The first is the trailblazing work of Dr. Ritchie Shoemaker on chronic inflammatory response syndrome (CIRS). This syndrome is induced primarily by mold biotoxins and the inflammagens of water-damaged buildings, ciguatera or pfiesteria infestations, or Lyme disease and co-infections. The second is the pioneering work of Dr. Lawrence Afrin on mast cell activation syndrome (MCAS). Dr. Afrin is a board-certified hematologist/oncologist who recently wrote a book, “Never Bet Against Occam: Mast Cell Activation Disease and the Modern Epidemics of Chronic Illness and Medical Complexity.”

Two important books that address the complex syndromes that may underlie many chronic, multisymptom, multisystem disease conditions are:

  • Surviving Mold: Life in the Era of Dangerous Buildings, by Ritchie C. Shoemaker, M.D.
  • Never Bet Against Occam: Mast Cell Activation Disease and the Modern Epidemics of Chronic Illness and Medical Complexity, by Lawrence B. Afrin, M.D.

What is Mast Cell Activation Syndrome?

What is MCAS? Mast cell activation syndrome (MCAS) refers to a group of disorders with diverse causes presenting with episodic multisystem symptoms as the result of mast cell mediator release, often without causing abnormalities in routine laboratory or radiologic testing. Most people with MCAS have chronic and recurrent inflammation, with or without allergic symptoms. This occurs when an aspect of the innate immune system becomes overactive and releases a flood of inflammatory chemicals, which may affect every organ in the body. The symptoms of MCAS will wax and wane over time. Another way to think of this is the symptoms will flare up and go into remission, affecting different organs and body parts, over and over again throughout a person’s life, without a common unifying theme or established diagnoses to account for the patient’s presentation of symptoms.

MCAS can present subtly but may become more serious as an individual ages. If you were to chart the symptoms of MCAS on a timeline, beginning at birth you can often identify symptoms that began at a very young age.

For some, MCAS becomes a highly probable diagnosis when they notice that they have had various symptoms of an inflammatory nature over the years. Mast cell activation syndrome symptoms may include:

  • Allergies as a toddler
  • Various skin rashes that came and went
  • Disturbed gut function (possibly diagnosed as irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD) or small intestinal bacterial overgrowth (SIBO))
  • Unexplained anxiety
  • Headaches
  • Insomnia
  • Poor wound healing

Any of these symptoms could indicate MCAS.

You can take our Hoffman Centre for Integrative Medicine MCAS Questionnaire HERE.

Dr. Afrin believes that MCAS is an epidemic with as many as 14 to 17 percent of the US population having MCAS – one out of every six to seven individuals. It has been said that it may take up to 10 years and numerous doctor visits before someone is adequately diagnosed and treated by a knowledgeable physician—or the patient figures it out for themselves!

What are Mast Cells, Mast Cell Mediators, and Histamine?

Mast cells are types of white blood cells that release up to 200 signalling chemicals, or mast cell mediators, into the body as part of an immune system stabilizing defense response against foreign invaders (parasites, fungi, bacteria, or viruses), allergens and environmental toxins.
We need mast cells to protect us from infection, heal wounds, create new blood cells, and develop immune tolerance. However, in conditions in which these cells are dysfunctional or overactive, they can cause serious issues.

Mast cells are found in most tissues throughout your body. In particular, they are found in tissues that are in close contact with the environment such as your skin, airways, and gastrointestinal tract. Mast cells are also found in your cardiovascular, nervous, and reproductive systems.

Mast cell mediators are the preformed granules secreted by mast cells in response to an outside stimulus, which can occur very quickly, in milliseconds. Mast cell mediators include histamine, proteases, leukotrienes, prostaglandins, chemokines, and cytokines. Their job is to signal and guide other cells, tissues, and organs to respond to the hostile invaders. These mast cell mediators provoke potent inflammatory responses that can include urticaria (AKA hives—skin rash and swelling), angioedema (swelling beneath the skin surface), bronchoconstriction (airway constriction), diarrhea, vomiting, hypotension (low blood pressure), cardiovascular collapse, and death, all within a matter of minutes.

Detailed Symptoms of Mast Cell Activation Syndrome

Patients who come into my office with MCAS usually have multisystem, multisymptom inflammatory responses. These symptoms have often caused them to trudge from doctor to doctor, undergoing rounds of testing, causing them to feel extraordinarily confused as to what’s happening to their body. Because the symptoms of MCAS have so broad a reach and differ so considerably from person to person I’d like to break them down by nonspecific, general clues, and organ system signs.

See Keith Berndtson’s (http://havenmedical.com/) slide below: Permission to use slide given by author.

 

Mast Cells The Bad

 

Histamine Intolerance & Mast Cell Activation

 

Most Common General MCAS Symptoms:

  • “I’ve been sick for as long as I can remember”
  • “I overreact to bee stings, mosquito bites, penicillin and most medications”
  • “I can’t take a full breath”
  • “Whenever I stand up I get lightheaded”
  • Insomnia/sleep disorders starting early in life
  • Tinnitus/ringing in the ears from a young age
  • Vomiting as an infant
  • Abdominal pain as an infant
  • Facial and chest flushing ( a red flush when embarrassed or stressed)
  • Dermatographism—a red line appearing on the skin when scratched with a blunt object
  • Frequent infections, cold, viruses, gut viruses as an infant, adolescent or adult
  • Fatigue and malaise
  • Frequent fevers
  • Edema—“water” accumulation in different parts of body
  • Waxing and waning of symptoms
  • Food, drug, and chemical intolerances (especially fragrances). This is a very common symptom which may be exacerbated by phase 1 and phase II liver detoxification problems as identified by gene testing
  • Sense of being cold all the time
  • Decreased wound healing
  • Hypersensitivity to much in environment, including medications
  • Weight gain or loss
  • Heat intolerance
  • Frequent family history of cancer, especially intestinal or bone marrow (hematologic)
  • Generally feeling inflamed
  • Generalized lymphadenopathy (enlarged lymph nodes)

MCAS Symptoms by Organ System

Eyes – Red eyes, irritated eyes, dry eyes, burning eyes, difficulty focusing vision, and conjunctivitis (pink eye).

Nose – Nasal stuffiness, sinusitis, postnasal drip, hoarseness, laryngitis, nose bleeds (epistaxis), and intranasal sores.

Ears – Ringing in ears (tinnitus) and Eustachian tube dysfunction (blocked, popping ears).

Throat – Vocal cord dysfunction, throat swelling, sores on tongue/mouth, itchy throat, burning mouth, and difficulty swallowing

Skin – Hives, angioedema (swelling of the skin), skin flushing, itching, skin rashes, dermatographism (when scratched skin causes a red welt), chronic itching, urticarial pigmentosa (legion/hive-like spots on the skin), flushing, bruising easily, reddish or pale complexion, cherry angiomata (skin growths), patchy red rashes, red face in the morning, cuts that won’t heal, fungal skin infections, and lichen planus.

Cardiovascular – Fainting, fainting upon standing, increased pulse rate (tachycardia), palpitations, spikes and drops in blood pressure, high pulse or temperature, high triglycerides, lightheadedness, dizzy, hot flashes, and postural orthostatic hypotension syndrome (POTS).

Respiratory – Wheezing, asthma, shortness of breath, difficulty breathing deep, air hunger, dry cough, chronic obstructive pulmonary disease (COPD), and chronic interstitial fibrosis.

GI Tract – Left upper abdominal pain, splenomegaly (enlarged spleen) epigastric tenderness, nausea, vomiting, diarrhea and/or constipation, abdominal cramping, bloating, non-cardiac chest pain, malabsorption, GERD/acid reflux, cyclic vomiting syndrome, colonic polyps, and gastric polyps.

Liver – High bilirubin, elevated liver enzymes, and high cholesterol.

Neurological – Numbness and tingling (especially in the hands and feet), headaches, migraines tics, tremors, pseudo-seizures, true seizures, waxing and waning brain fog, memory loss, poor concentration, difficulty finding words, and spells of cataplexy (suddenly becoming disconnected from and unresponsive or unreactive to the world around).

Musculoskeletal – Muscle pain, fibromyalgia, increased osteopenia, osteoporosis, weakness, and migratory arthritis (joint pain).

Coagulation – History of clots, deep vein thrombosis, increased bruising, heavy menstrual bleeding, bleeding nose, and cuts that won’t stop bleeding.

Blood disorders – Anemia, increased white blood cell count, platelets, decreased white blood cell counts, decreased neutrophils, decreased lymphocytes, decreased platelets, reductions in CD4 helper lymphocytes, reductions in CD8 positive suppressor lymphocytes, reductions or excesses of IgA, IgG, IgM, IgE, a known condition called MGUS, myelodysplastic syndrome (reduced red cells, white cells, platelets), and increased MCV (mean corpuscular volume).

Psychiatry – Anxiety, panic, depression, obsessive compulsive disorder (OCD), decreased attention span, attention deficit/hyperactivity disorder (ADHD), forgetfulness, and insomnia.

Genitourinary – Interstitial cystitis, recurrent bladder infections, sterile bladder infections, and frequent urination.

Hormones – Decreased libido, painful periods, heavy periods, infertility, and decreased sperm counts.

Dental – Deteriorating teeth.

Anaphylaxis – Difficulty breathing, itchy hives, flushing or pale skin, feeling warm after exposure, weak and rapid pulse, nausea, vomiting, diarrhea, dizziness and fainting.

Illnesses Associated with MCAS

There are a number of illnesses and conditions that can exacerbate MCAS, including chronic inflammatory response syndrome (CIRS), poor methylation as determined by genetic MTHFR defects (leading to low SAMe, which degrades histamine intracellularly), deficiencies in histamine-N-methyltransferase enzyme (HNMT; degrades histamine in the liver) and deficiencies in the gut-based diamine oxidase (DAO) enzyme, which degrades histamine found in food. Histamine is one of the many inflammatory mediators released by individuals with MCAS. For those with healthy DAO levels, nearly all the histamine derived from food sources are broken down by their DAO enzymes.

But when there’s a lack of DAO, a DAO deficiency, histamine can assist in creating intestinal permeability and upregulated inflammation. If a person suffers from small bowel intestinal overgrowth (SIBO) or has significant small intestinal issues (called dysbiosis), the lining of the small intestine may be disrupted. This leads to even lower levels of the DAO enzyme and hence, intestinal permeability.

Here’s a relatively common situation:

A woman who struggles with chronic fatigue and malaise throughout her life gets pregnant and suddenly feels energetic and wonderful throughout her pregnancy. Studies suggest this could be because DAO levels are up to 500 times higher than normal during normal pregnancies.

Alternatively, a person who was previously quite healthy develops a bacterial infection, is prescribed a 10-day course of antibiotics and suddenly develops severe reactions to certain foods. When looked at closely, these foods are found to contain high histamine levels. The current fads of consuming bone broths and fermented foods such as sauerkraut and kombucha only help to exacerbate this condition.

Histamine can have a powerful effect on a person’s wellbeing, making it important to be aware of the symptoms that indicate MCAS.

Histamine Intolerance is a Subset of MCAS

Mast cell activation syndrome (also referred to as mast cell activation disorder (MCAD)) is sometimes confused with histamine intolerance. The major difference is that with MCAS and mast cell activation disorder, a person’s mast cells secrete many mediators of inflammation, such as leukotrienes and prostaglandins, not just histamine—although histamine is an important component. Histamine intolerance is considered a subset of MCAS where too much histamine is released from mast cells, too much histamine is taken in by consuming histamine-containing foods, histamine is not broken down in the gut because of DAO gut enzyme deficiency, or not broken down in the liver because of HNMT deficiency.

However, histamine is not all bad; it serves useful functions as a neurotransmitter, helps to produce stomach acid, and is an important immune mediator when not in excess.

Diagnosis of Mast Cell Activation Syndrome

A proper diagnosis of mast cell disorder requires the presence of several symptoms from the above list. In addition, other disorders should be ruled out by a specialist in functional medicine.

MCAS is so difficult to diagnose because it may present in so many varied ways that traditional health care providers are not always trained to assess. There is a tremendous range of possible presentations, with local and remote effects which wax and wane over time.

If MCAS is suspected at our office, I send patients home with Chapter 6 of the book Mast Cells – Phenotypic Features, Biological Functions and Role in Immunity by David Murray. This chapter was written by Dr. Afrin, entitled Presentation, Diagnosis, and Management of Mast Cell Activation Syndrome. It describes, system by system, most of the symptoms that can be attributed to this diagnosis. Patients then return the symptom check list, which we review together slowly in order to establish the clinical diagnosis. I then order the lab tests to prove its existence.

In Dr. Afrin’s own words, “The general presenting motif of MCAS is chronic multisystem polymorbidity, generally of an inflammatory theme and with assorted elements waxing and waning over time, sometimes in synchronization with one another but more often cycling with different periods and amplitudes. The range of mast cell mediators and their effects is so great that “unusual” presentations actually become de riguer.”

Lab tests can be done to check for mast cell mediators. Tryptase is one of the most common mediators released by mast cells in those with mastocytosis (abnormal numbers of mast cells), but not for those with MCAS (abnormal release of proinflammatory mediators by mast cells, but not an increased number, as in the much rarer mastocytosis). Lab tests can also check for other mediators, such as histamine and prostaglandins; however, most doctors and many labs, particularly those in Canada, will not run the tests that are required to make the diagnosis.

Sometimes patients are able to identify triggers of their MCAS. These may be food or non-food triggers. Pay close attention to what you’ve eaten and have been exposed to when symptoms worsen.

After symptoms have been identified, other conditions have been ruled out, lab tests have been analyzed, and some treatment techniques have proven to relieve symptoms, an official diagnosis of MCAS is made.

In an effort to help you notice common triggers, below are 10 non-food and 10 food triggers that commonly provoke mediator release in those with MCAS.

10 Non-Food Triggers of Mast Cell Activation Syndrome

If you’re struggling or suspect you have MCAS, it’s in your best interest to reduce your exposure to these triggers, including:

  1. Extreme temperatures – either hot or cold
  2. Exposure to mold or Lyme disease and coinfections
  3. Emotional stress
  4. Insect bites
  5. Chemicals in personal products
  6. Medications that liberate histamine or block DAO
  7. Sodium benzoate –a common food preservative
  8. Airborne smells from chemicals or smoke
  9. Heavy metal toxicity – aluminum, mercury, lead, cadmium, bismuth and arsenic are known to be mast cell destabilizers
  10. Anesthetics

10 High Histamine Foods that Should be Avoided

Studies have shown that eliminating foods high in histamine and other triggers can significantly improve symptoms. Ten of the highest histamine foods include:

  1. Yeast and alcohol
  2. Dairy (especially fermented dairy like kefir)
  3. Gluten
  4. Fermented foods, especially sauerkraut, kombucha, miso
  5. Cured and smoked meats and fish
  6. Shellfish
  7. Citrus foods – lemon, lime, orange
  8. Vinegar
  9. Leftover and aged food – especially if left in the refrigerator and not frozen immediately
  10. Berries – strawberries, blueberries, raspberries

Conditions Associated with Mast Cell Activation Syndrome

Because MCAS is a chronic, multisystem, multisymptom condition with an inflammatory theme, it’s been associated with a number of conditions and diseases, including:

  • Chronic inflammatory response syndrome
  • Irritable bowel syndrome
  • Gut dysbiosis – the gut is rich in mast cells and home to over 70% of the immune system. Parasites, bacteria, fungi, and parasites can all trigger gut mast cells.
  • Obesity
  • Diabetes
  • Asthma and allergies
  • Autism
  • Autoimmune diseases (such as lupus, rheumatoid arthritis, and Hashimoto’s)
  • Candida overgrowth
  • Celiac disease
  • Parasite infections
  • Skin conditions such as eczema and psoriasis
  • Food intolerances and allergies
  • Gastroesophageal reflux (GERD)
  • Infertility and endometriosis
  • Chemical and medication sensitivities
  • Postural orthostatic hypotension (POTS)
  • CIRS – exposure to mold mycotoxins is a potent stimulator of mast cell activation
  • Migraines
  • Depression
  • Fibromyalgia
  • Fungal infections
  • Tinnitus
  • Multiple Sclerosis
  • Cancer

In general, inflammation accompanies MCAS and most of its coinciding or associated illnesses. If you are struggling to get one of these illnesses under control, there’s a possibility MCAS could be causing further complications.

It’s a good idea to check for MCAS if you have any of the above conditions and vice versa.

You can take our Hoffman Centre for Integrative Medicine MCAS Questionnaire HERE.

Ask Your Doctor for Lab Work

MCAS can be difficult to diagnose because lab test results may fluctuate as symptoms wax and wane. Many tests may need to be repeated during times of symptom flare-ups. Poor handling of specimens by the laboratory is also a real issue affecting results. Lab testing may thus result in false negatives despite a clinical history highly consistent with MCAS. Furthermore, MCAS doesn’t always cause abnormalities in lab work, adding to the complexity of diagnosis. Positive lab work is obtained only 20% of the time.

If you’re interested in getting lab work done to check for MCAS, I recommend the tests listed below. The top five, in bold, are the most important and necessary to establish a diagnosis:

  1. Histamine – plasma – Quest 36586 – must be chilled. Normal range – 28-51 ug/l.
  2. N-Methylhistamine – 24-hour urine – must be chilled. Normal range – less than 200 mcg/g.
  3. Prostaglandin D2 – plasma – must be chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  4. Prostaglandin D2 (PGD2) – 24-hour urine – chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  5. Chromogranin A – Quest 16379 – must be off proton pump inhibitors (PPIs) and H2 blockers (Pepcid and Zantac) for 5 days before tests, since they can falsely elevate chromogranin A.
  6. Prostaglandin 11-beta F2 Alpha (PGF2alpha) – 24-hour urine – chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  7. Serum Tryptase – Quest 34484. Rarely elevated in MCAS. NR less than 11.5 ng/ml. Positive if increase over baseline of 20% or baseline greater than 15.
  8. Leukotriene E4 – 24-hour urine – chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  9. Plasma heparin Anti-XA (must be off heparin products) – chilled. Degrades quickly.
  10. Blood clotting profile – Thrombin/PT/PTT/INR.
  11. Anti-IgE Receptor antibody.
  12. Neuron Specific Enolase – Quest 34476.
  13. Plasma pheochromocytoma workup.
  14. Porphyria workup.
  15. Factor VIII deficiency.
  16. Plasma free norepinephrine – Quest 37562.
  17. Urinary metanephrines – can b done in normal Calgary labs.
  18. Immunoglobulins – IgG, IgM, IgE, IgA
  19. Bone marrow biopsy looking for the following markers: CD117/CD25; CD117/CD2.
  20. Gastrin
  21. Ferritin
  22. CBC – eosinophils, basophils.
  23. Antiphospholipid antibodies.
  24. Genetic testing looking for Phase 1 and Phase II liver detox and methylation defects.
  25. Dunwoody Labs – test zonulin, histamine, DAO enzyme deficiency.

Many of these tests require specimens that are chilled by using a special centrifuge as the mast cell mediators are fleeting and degrade very quickly if not handled properly.

Further tests that may be of help:

  1. MTHFR gene mutations
  2. MAT gene mutations
  3. DAO gene mutations
  4. HNMT gene mutations. The liver plays a role in histamine intolerance. Histamine is not just disassembled in the gut by diamine oxidase (DAO). It is also disassembled in the liver, where it is in high concentrations, by HNMT.
  5. Glutathione levels. If glutathione levels are depleted, the inflammatory mediators released by mast cells may not be adequately neutralized by glutathione, the master antioxidant. This can lead to a vicious circle where oxidative stress results in mast-cells releasing inflammatory chemicals, which need to be detoxified by Phase 1 of the liver. If glutathione is low, the liver will be unable to neutralize them, resulting in further inflammation and oxidative stress.

These tests can help you identify whether MCAS is the cause of your mysterious and seemingly unrelated symptoms.

Treatments for Lowering Histamine and Reducing MCAS Symptoms

Now, you might be thinking, “Why can’t I just take an antihistamine?”

Antihistamines don’t actually reduce histamine release. They only block histamine receptors, preventing you from feeling the symptoms. You may need a round-the-clock blockade of the H1 and H2 receptors, every 12 hours.

If you want lasting relief for MCAS:

  • Histamine 1 blockers – hydroxyzine, doxepin, loratadine, fexofenadine, diphenhydramine, ketotifen, and cetirizine.
  • Histamine 2 blockers – famotidine (Pepcid, Pepcid AC), cimetidine (Tagamet, Tagamet HB), ranitidine (Zantac). Famotidine is chosen most often as it has fewer drug interactions than Tagamet).
  • Mast cell stabilizers – cromolyn, ketotifen (both a mast cell stabilizer and an H1 blocker), hydroxyurea, quercetin.
  • Leukotriene inhibitors – montelukast (Singulair), zafirlukast (Accolate)
  • Tyrosine kinase inhibitors.

H1 and H2 blockers must be taken every 12 hours for maximum effect. It may take up to 12 months to achieve maximum therapeutic effect. The doses may need to be increased to up to three times the recommended over-the-counter dosing.

Here is how I approach treatment with my MCAS patients:

  • Eat a low-histamine diet: Remove alcohol, smoked and cured meat, tinned fish, pickled and fermented foods, berries (strawberries being one of the worst culprits), citrus, nuts, chocolate, dairy, spinach, yeast, soy sauce, tomatoes and tomato products, preservatives, and vinegar. Stop eating leftover food. This will only reduce the incoming histamine and won’t affect the mast cell overactivity within the cells of the body. A comprehensive guide regarding the low-histamine diet can be found here.
  • Promote good gut health: Cut back on gut-damaging and inflammatory foods, and increase probiotics. Use a DAO enzyme, which goes under the generic name Umbrellux DAO – two tablets, 20 minutes before each meal.
  • Stabilize mast cell release of histamine with quercetin and vitamin C 500 mg – two tablets three times daily. We use a product called Natural-D Hist from Ortho Molecular Products.
  • Use H1 and H2 blockers every 12 hours – I use, on average, levocetirizine 5 mg twice daily and famotidine 20 mg twice daily.
  • Block nighttime histamine release with ketotifen or zaditen – 0.25–1 mg at night. Excellent sleep aid, mast cell stabilizer, H1 antihistamine. Excellent treatment for eosinophilic esophagitis.
  • Treat any existing infections: Have a thorough examination done to identify and treat any potential infections in the body which are powerful mast cell triggers. Stool testing by Genova labs and Cyrex Lab Pathogen Testing (array 12) can be of assistance in identifying pathogens.
  • Identify and remove toxins and allergens: This could be heavy metals, mercury fillings, cosmetics, and household cleaners.
  • Nutrients that assist in the treatment: This includes vitamin B6, alpha lipoic acid, vitamin C and E, selenium, omega-3s, N-acetylcysteine (NAC), methylation donors like methyl-folate, SAMe, and riboflavin.
  • Herbs: Nigella sativa, butterbur, turmeric, ginger and peppermint.
  • Get into a solid routine: Getting high quality sleep and staying on schedule helps keep mast cells in check.
  • Reduce stress: Stress, through the action of corticotropin hormone, can activate your mast cells and cause them to destabilize and release mediators.
  • One of the best resources for how to deal with histamine and mast cell activation through nutrition and supplementation is the website and Facebook posts by Yasmina Ykelenstam www.healinghistamine.com.

It can be incredibly discouraging to feel so sick for so long and not find any answers. It is my hope that we continue to learn more about multisystem conditions such as MCAS and spread useful information so it may end up in the hands of those suffering.

Share this article with friends and family to help spread the word about MCAS symptoms. They may discover it’s more than allergies that’s keeping them down.

Resources

Yasmina Ykelenstam – excellent resource:  www.healinghistamine.com.

Dr. Afrin’s website – the main researcher:  www.mastcellresearch.com. Many links to mast cell information are available on this website.

Dr. Theoharides – another major researcher: http://www.mastcellmaster.com/

Hoffman Centre for Integrative Medicine MCAS Questionnaire: https://hoffmancentre.com/wp-content/uploads/2017/11/7.-Mast-Cell-Activation-Syndrome-Clinical-Questionniare-November-7-2017.pdf

https://www.youtube.com/watch?v=82dmZhCBuBo

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753019/

https://ehlers-danlos.com/2014-annual-conference-files/Anne%20Maitland.pdf

https://tmsforacure.org/symptoms/symptoms-and-triggers-of-mast-cell-activation/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231949/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343118/

https://www.ncbi.nlm.nih.gov/pubmed/16931289

https://www.ncbi.nlm.nih.gov/pubmed/17587883

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069946/

https://www.ncbi.nlm.nih.gov/pubmed/22957768

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545645/

https://academic.oup.com/humupd/article/14/5/485/812106/Effects-of-histamine-and-diamine-oxidase

https://www.ncbi.nlm.nih.gov/pubmed/24098785

http://ajcn.nutrition.org/content/85/5/1185.long

https://link.springer.com/article/10.1007/BF01997363

https://www.ncbi.nlm.nih.gov/pubmed/25773459

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507480/

https://www.ncbi.nlm.nih.gov/pubmed/15462834

https://www.ncbi.nlm.nih.gov/pubmed/22562473

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374363/

https://www.ncbi.nlm.nih.gov/pubmed/21244748

https://www.ncbi.nlm.nih.gov/pubmed/23784732

https://www.ncbi.nlm.nih.gov/pubmed/18394691

https://www.ncbi.nlm.nih.gov/pubmed/24060274

https://www.ncbi.nlm.nih.gov/pubmed/10415589

Diagnosing MCAS – Ask Your Doctor for Lab Work

Ask Your Doctor for Lab Work

MCAS can be difficult to diagnose because lab test results may fluctuate as symptoms wax and wane. Many tests may need to be repeated during times of symptom flare-ups. Poor handling of specimens by the laboratory is also a real issue affecting results. Lab testing may thus result in false negatives despite a clinical history highly consistent with MCAS. Furthermore, MCAS doesn’t always cause abnormalities in lab work, adding to the complexity of diagnosis. Positive lab work is obtained only 20% of the time.

If you’re interested in getting lab work done to check for MCAS, I recommend the tests listed below. The top five, in bold, are the most important and necessary to establish a diagnosis:

  1. Histamine – plasma – Quest 36586 – must be chilled. Normal range – 28-51 ug/l.
  2. N-Methylhistamine – 24-hour urine – must be chilled. Normal range – less than 200 mcg/g.
  3. Prostaglandin D2 – plasma – must be chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  4. Prostaglandin D2 (PGD2) – 24-hour urine – chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  5. Chromogranin A – Quest 16379 – must be off proton pump inhibitors (PPIs) and H2 blockers (Pepcid and Zantac) for 5 days before tests, since they can falsely elevate chromogranin A.
  6. Prostaglandin 11-beta F2 Alpha (PGF2alpha) – 24-hour urine – chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  7. Serum Tryptase – Quest 34484. Rarely elevated in MCAS. NR less than 11.5 ng/ml. Positive if increase over baseline of 20% or baseline greater than 15.
  8. Leukotriene E4 – 24-hour urine – chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  9. Plasma heparin Anti-XA (must be off heparin products) – chilled. Degrades quickly.
  10. Blood clotting profile – Thrombin/PT/PTT/INR.
  11. Anti-IgE Receptor antibody.
  12. Neuron Specific Enolase – Quest 34476.
  13. Plasma pheochromocytoma workup.
  14. Porphyria workup.
  15. Factor VIII deficiency.
  16. Plasma free norepinephrine – Quest 37562.
  17. Urinary metanephrines – can b done in normal Calgary labs.
  18. Immunoglobulins – IgG, IgM, IgE, IgA
  19. Bone marrow biopsy looking for the following markers: CD117/CD25; CD117/CD2.
  20. Gastrin
  21. Ferritin
  22. CBC – eosinophils, basophils.
  23. Antiphospholipid antibodies.
  24. Genetic testing looking for Phase 1 and Phase II liver detox and methylation defects.
  25. Dunwoody Labs – test zonulin, histamine, DAO enzyme deficiency.

Many of these tests require specimens that are chilled by using a special centrifuge as the mast cell mediators are fleeting and degrade very quickly if not handled properly.

Further tests that may be of help:

  1. MTHFR gene mutations
  2. MAT gene mutations
  3. DAO gene mutations
  4. HNMT gene mutations. The liver plays a role in histamine intolerance. Histamine is not just disassembled in the gut by diamine oxidase (DAO). It is also disassembled in the liver, where it is in high concentrations, by HNMT.
  5. Glutathione levels. If glutathione levels are depleted, the inflammatory mediators released by mast cells may not be adequately neutralized by glutathione, the master antioxidant. This can lead to a vicious circle where oxidative stress results in mast-cells releasing inflammatory chemicals, which need to be detoxified by Phase 1 of the liver. If glutathione is low, the liver will be unable to neutralize them, resulting in further inflammation and oxidative stress.

These tests can help you identify whether MCAS is the cause of your mysterious and seemingly unrelated symptoms.

[embed_popupally_pro popup_id="5"]

Depression, SSRIs and Self-Advocacy

Depression

A recent study has concluded that SSRIs, when treating for major depressive disorder, are not that much better than placebo. Depression as a symptom and as a formal diagnosis, is too simple a label to attribute to a person who feels and experiences life without joy or pleasure and who may have real physiological changes that render his/her life unpleasant, if not unbearable. By attributing a diagnosis to a person such as “depression,” the patient and the diagnosis become frozen in time and separated from all possible antecedents, mediators and triggers. All further enquiry into the timeline of causation comes to an end and the patient (and the doctor) now objectify and identify with the diagnosis, as if some foreign entity, called “depression” just mysteriously fell out of the sky.  Add to this scenario the fact that ones entire medical school training is not aimed to enquire as to upstream causation. In the truest N2D2 tradition of medicine (name of disease, name of drug), we are trained to thread together a constellation of symptoms, arrive at a diagnosis and prescribe a treatment1; all under the 15 minute timeline and the approximately $40.00 fee that the Canadian health care system provides for a consultation. It does not take much to deduce that this is a hopelessly inadequate scenario and not one to foist onto ones worst enemy.

Depression, as a diagnosis, has a litany of possible antecedents (ancestral and genetic predispositions and inheritances), triggers (events that trigger the manifestation of the constellation of symptoms that coalesce to form a diagnosis) and mediators (lifestyle events and behaviours – diet, sleep, food, stress, exercise – that continue to contribute to the diagnosis). From ancestral trauma (that we now know to be epigenetically inherited), to early conception and birth trauma, to adverse childhood experiences and complex trauma, to head injuries, to genetic weaknesses in detoxification and methylation (creating scenarios of over and undermethylation) nutritional and hormonal inadequacies, to toxic insults such as mercury, lead, copper toxicity, mold, Lyme disease and co-infections, to sleep apnoea, to relationship struggles, workplace difficulties, transition from first half of life ego demands to second half of life soul demands; the list is long and complex.

Self-Advocacy

Unless doctors/healers of the future are trained in a new paradigm (Functional Medicine is putting up a valiant effort to educate future health care providers in this methodology), have sufficient life experience and have spent a large portion of their learning years investigating and researching the multiple layers and levels of complexity (7 Stages to Health and Transformation) that may contribute to the origins and continuations of  symptom or disease processes, you, as a health care consumer, will always be at the mercy of their experience (or inexperience) along this continuum. That is why it is imperative that all patients, as much as they can muster the lifeforce to do so, become advocates of their own health and treatment protocols. Patient self-advocacy, combined with a serious intent to do what it takes to get well, is always at the root of successful health outcomes. Or, if faced with a depressive illness or episode, we can hand over all power to the physician/healer we have consulted, take an antidepressant and hope for the best. Your choice.

Resources

  1. https://www.ncbi.nlm.nih.gov/pubmed/28178949

Treatments for Lowering Histamine and Reducing MCAS Symptoms

Treatments for Lowering Histamine and Reducing MCAS Symptoms

Now, you might be thinking, “Why can’t I just take an antihistamine?”

Antihistamines don’t actually reduce histamine release. They only block histamine receptors, preventing you from feeling the symptoms. You may need a round-the-clock blockade of the H1 and H2 receptors, every 12 hours.

If you want lasting relief for MCAS:

  • Histamine 1 blockers – hydroxyzine, doxepin, loratadine, fexofenadine, diphenhydramine, ketotifen, and cetirizine.
  • Histamine 2 blockers – famotidine (Pepcid, Pepcid AC), cimetidine (Tagamet, Tagamet HB), ranitidine (Zantac). Famotidine is chosen most often as it has fewer drug interactions than Tagamet).
  • Mast cell stabilizers – cromolyn, ketotifen (both a mast cell stabilizer and an H1 blocker), hydroxyurea, quercetin.
  • Leukotriene inhibitors – montelukast (Singulair), zafirlukast (Accolate)
  • Tyrosine kinase inhibitors.

H1 and H2 histamine blockers must be taken every 12 hours for maximum effect. It may take up to 12 months to achieve maximum therapeutic effect. The doses may need to be increased to up to three times the recommended over-the-counter dosing.

Here is how I approach treatment with my MCAS patients:

  • Eat a low-histamine diet: Remove alcohol, smoked and cured meat, tinned fish, pickled and fermented foods, berries (strawberries being one of the worst culprits), citrus, nuts, chocolate, dairy, spinach, yeast, soy sauce, tomatoes and tomato products, preservatives, and vinegar. Stop eating leftover food. This will only reduce the incoming histamine and won’t affect the mast cell overactivity within the cells of the body. A comprehensive guide regarding the low-histamine diet can be found here.
  • Promote good gut health: Cut back on gut-damaging and inflammatory foods, and increase probiotics. Use a DAO enzyme, which goes under the generic name Umbrellux DAO – two tablets, 20 minutes before each meal.
  • Stabilize mast cell release of histamine with quercetin and vitamin C 500 mg – two tablets three times daily. We use a product called Natural-D Hist from Ortho Molecular Products.
  • Use H1 and H2 blockers every 12 hours – I use, on average, levocetirizine 5 mg twice daily and famotidine 20 mg twice daily.
  • Block nighttime histamine release with ketotifen or zaditen – 0.25–1 mg at night. Excellent sleep aid, mast cell stabilizer, H1 antihistamine. Excellent treatment for eosinophilic esophagitis.
  • Treat any existing infections: Have a thorough examination done to identify and treat any potential infections in the body which are powerful mast cell triggers. Stool testing by Genova labs and Cyrex Lab Pathogen Testing (array 12) can be of assistance in identifying pathogens.
  • Identify and remove toxins and allergens: This could be heavy metals, mercury fillings, cosmetics, and household cleaners.
  • Nutrients that assist in the treatment: This includes vitamin B6, alpha lipoic acid, vitamin C and E, selenium, omega-3s, N-acetylcysteine (NAC), methylation donors like methyl-folate, SAMe, and riboflavin.
  • Herbs: Nigella sativa, butterbur, turmeric, ginger and peppermint.
  • Get into a solid routine: Getting high quality sleep and staying on schedule helps keep mast cells in check.
  • Reduce stress: Stress, through the action of corticotropin hormone, can activate your mast cells and cause them to destabilize and release mediators.
  • One of the best resources for how to deal with histamine and mast cell activation through nutrition and supplementation is the website and Facebook posts by Yasmina Ykelenstam www.healinghistamine.com.

It can be incredibly discouraging to feel so sick for so long and not find any answers. It is my hope that we continue to learn more about multisystem conditions such as MCAS and spread useful information so it may end up in the hands of those suffering.

Share this article with friends and family to help spread the word about mast cell activation syndrome and histamine blockers. They may discover it’s more than allergies that’s keeping them down.

[embed_popupally_pro popup_id=”5″]