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 bills Making occasional errors but none that are significant or out of the ordinary
Struggling to complete familiar tasks such as driving home or to work Needing help setting up new equipment or electronics
Losing track of dates, seasons, or time Temporarily forgetting the day but having the ability to recall it later
Difficulty judging distance, spatial relationships, and contrast Worsening vision caused by cataracts
Trouble recalling words for things, following conversations, and speaking Occasionally having difficulty finding the preferred word while not forgetting names of items
Misplacing items and not being able to retrace steps Being 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 withdrawal Preferring to socialize a bit less
Changes in personality and mood Becoming 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.

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. 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.

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.clinicaleducation.org/resources/reviews/36-holes-in-the-roof-the-dawn-of-the-era-of-treatable-and-preventable-alzheimers-disease/#_ftn1

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/

https://www.clinicaleducation.org/resources/reviews/36-holes-in-the-roof-the-dawn-of-the-era-of-treatable-and-preventable-alzheimers-disease/

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 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 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.

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

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 MCAS 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:

  • 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 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.

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.

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?

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. These 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 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, 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, 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 MCAS 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 mast cell activation syndrome. 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.

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 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. They may discover it’s more than allergies that’s keeping them down.

Kryptopyrroluria (aka Hemopyrrollactamuria) 2017: A Major Piece of the Puzzle in Overcoming Chronic Lyme Disease

Dietrich Klinghardt, MD, PhD, is a practicing physician in Woodinville, Washington with a focus on the treatment of chronic neurological conditions such as Lyme disease, autism, and CFIDS. In the years that he has treated patients with chronic infections, he has observed that, for many, recovery is often elusive. Patients may plateau or find that their recovery is stalled. In other cases, patients may not succeed in their attempts to rid the body of a particular toxic or infectious burden, such as in patients with longstanding or therapy-resistant, late-stage Lyme disease.

In looking for possible explanations as to why some patients struggle more than others to regain their health, coauthor Klinghardt has found a high correlation between patients with chronic Lyme disease and those with kryptopyrroluria (KPU), or more precisely hemopyrrollactamuria (HPU). The condition is alternatively known as the “mauve factor” or “malvaria.”

KPU may be an inherited condition, but it can also be induced by psychological trauma or chronic infections. Epigenetic influences such as intrauterine, birth, childhood, or transgenerational trauma may trigger KPU; other triggers may include a car accident, divorce or emotional trauma, and physical or sexual abuse. Chronic infections, such as Lyme disease, may themselves serve as a trigger for the condition.

The HPU complex is a biochemical marker and neurotoxic substance frequently identified in the urine of patients with autism, learning disabilities, alcoholism, substance abuse, schizophrenia, ADHD, Down syndrome, depression, bipolar disorders, and even criminal behavior. Some estimate the incidence of KPU to be 40-70% in schizophrenia, 50% in autism, 30% in ADHD, and 40-80% in alcoholism and substance abuse.

Based on testing with Klinisch Ecologisches Allergie Centrum (KEAC; http://www.hputest.nl) in Holland,
Klinghardt has found the incidence of KPU in Lyme disease to be 80% or higher; in patients with heavy metal toxicity (lead, mercury, aluminum, cadmium, and others) over 75%; and in children with autism over 80%. These are very significant percentages of the patient population with chronic illness that may benefit from a treatment program that addresses KPU. Healthy controls do not test positive for KPU.

History

In 1958, a psychiatric research program in Saskatchewan, Canada, led by Abram Hoffer, MD, PhD, the father of orthomolecular psychiatry, was looking for the possible biochemical origin of schizophrenia and a lab marker that would make it easier to identify affected individuals. One study involved evaluating the urine for certain chemical fractions and evaluating those of schizophrenic patients and those of normal controls. The effort yielded “the mauve factor,” a specific substance that reliably allowed the examiners to identify the schizophrenic
patients, as it was not found in the normal controls.

Early on, the substance was known as “the mauve factor” due to the mauve color that was observed on the stained paper. It was then termed “kryptopyrrole”, later identified as hydroxyhemopyrrolin-2-one (HPL). The researchers first called the disease associated with this condition “malvaria,” but it was renamed by Dr. Carl Pfeiffer, MD, PhD to “pyrolleuria” which was, for no obvious reason, consistently spelled “pyrroluria” in later publications. Today, the condition is generally referred to as “pyroluria.” In the 1970s, Dr. Pfeiffer created an assay for the condition and was able to show clinical improvement in positive patients with high doses of zinc and vitamin B6 (between 400 mg and 3,000 mg B6).

Associated Conditions

A partial list of conditions where KPU may be a factor includes ADHD, alcoholism, autism, bipolar disorders, criminal behavior, depression, Down syndrome, epilepsy, heavy metal toxicity, learning disabilities, Lyme disease, multiple sclerosis, Parkinson’s disease, schizophrenia, and, substance abuse. The items listed in bold are those in which Klinghardt has observed a connection to KPU in his patient population.

Symptoms

The KPU condition results in a significant loss of zinc, vitamin B6, biotin, manganese, arachidonic acid, and other nutrients from the body via the kidneys. There are many symptoms of KPU, which may result from deficiencies of these nutrients. Those in bold are tell-tale signs of the condition. Klinghardt finds that depression is often a leading symptom of the condition. Symptoms may include the following:

  • Abdominal tenderness
  • Abnormal fat distribution
  • Acne, allergy
  • Amenorrhea, irregular periods
  • Anxiety / Nervousness
  • Attention Deficit / ADHD
  • Autism
  • B6-responsive anemia
  • Cold hands or feet
  • Constipation
  • Course eyebrows
  • Crime and Delinquency
  • Delayed puberty, impotence
  • Depression
  • Emotional liability
  • Eosinophilia
  • Explosive or episodic anger
  • Familial
  • Hypoglycemia, glucose intolerance
  • Knee and joint pain
  • Light, sound, odor intolerance
  • Mood swings
  • Nail spots (Leukodynia)
  • Obesity
  • Pale skin, poor tanning
  • Paranoia / Hallucinations
  • Perceptual disorganization
  • Pessimism
  • Poor breakfast appetite
  • Poor Dream Recall
  • Poor short-term memory
  • Stress intolerance
  • Stretch marks (striae)
  • Substance abuse
  • Tremor, shaking, spasms
  • Withdrawal

Impact of Nutrient Loss

Elevated levels of HPL found in urine are the result of an abnormality in heme synthesis. Hemoglobin is the substance that holds iron in the red blood cells. Heme is also the principal building block of many enzymes involved in detoxification (cytochromes), enzymes involved in healthy methylation (MSR and CBS), and NOS – a significant enzyme in the urea/BH4-cycle. HPL is a byproduct of dysfunctional heme synthesis and can be identified in the urine. HPL binds to zinc, vitamin B6, biotin, manganese, arachidonic acid (omega-6), and other important compounds that, as a result, are excreted via the urine.

This leads to a significant depletion of these nutrients throughout the body and to the synthesis of non-functioning or poorly functioning enzymes. Turning to the importance of zinc, vitamin B6, biotin, manganese, and arachidonic acid in the body, it becomes clear how widespread the problems may be that are created by this condition.

Zinc deficiency may result in emotional disorders, food allergies, insulin resistance, delayed puberty, rough skin, delayed wound healing, growth retardation, hypogonadism, hypochlorhydria, mental lethargy, short stature, diarrhea, stretch marks or striae (which may be misinterpreted as Bartonella in some patients with Lyme disease), white spots on the fingernails, reduction in collagen, macular degeneration, dandruff, skin lesions such as acne, hyperactivity, loss of appetite, reduced fertility and libido, transverse lines on the fingernails, defective mineralization of the bones leading to osteoporosis, and many others.

Zinc is a powerful antioxidant, and lower levels lead to an increase in oxidative stress. Lower levels are correlated with lowered glutathione, an important part of the detoxification system. Zinc is required to support proper immune function. “White blood cells without zinc are like an army without bullets,” says Klinghardt.

Vitamin B6 deficiency is thought to be a rare occurrence. However, in those with KPU, this is not the case. B6 deficiency may lead to nervousness, insomnia, irritability, seizures, muscle weakness,
poor absorption of nutrients, decrease of key enzymes and cofactors involved in amino acid metabolism, impairment in the synthesis of neurotransmitters, impairment in the synthesis of hemoglobin, seborrheic dermatological eruptions, confusion, and neuropathy. Like zinc, B6 is an antioxidant and correlates to levels of glutathione.

Biotin deficiency may be evidenced by rashes, dry skin, seborrheic dermatitis, brittle nails, fine or brittle hair, and hair loss. More importantly, however, it may be associated with depression, lethargy, hearing loss, fungal infections, muscle pain, and abnormal skin sensations such as tingling. Biotin is an important co- factor in the production of energy in the mitochondria. Biotin is essential for a healthy brain and nervous system. Biotin deficiency is associated with many aspects of the aging process.

Manganese deficiency may be associated with joint pain, inflammation, and arthritis. Deficiency may result in a change in hair pigment or a slowing of hair growth. It is essential for normal growth, glucose utilization, lipid metabolism, and production of thyroid hormone. It may be associated with diseases such as diabetes, dyslipidemia, Parkinson’s disease, osteoporosis, and epilepsy.

Arachidonic acid (from omega-6) deficiency may lead to the impairment of white blood cell function, primarily the leukocytes, which may lead to one being more vulnerable to infection. It may lead to neuropathy, neural and vascular complications in preterm babies, skin eruptions, behavior changes, sterility in males, arthritic conditions, dry eyes, growth retardation, dry skin and hair, slow wound healing, hair loss, kidney dysfunction, heart beat abnormalities, and miscarriages.

When one considers the magnitude of potential health problems that may be present when a single condition leads to a deficiency in zinc, vitamin B6, biotin, manganese, arachidonic acid, and other nutrients simultaneously, the negative implications on health are almost endless.

KPU and Lyme Disease

Three possible origins of KPU are discussed in the literature: genetics, trauma, and chronic infections. The connection between KPU and many of the illnesses previously discussed has been known for quite some time. However, prior to Klinghardt’s early work in treating Lyme disease, never before had a connection been observed or published between KPU and Lyme disease. This discovery has been a key for Klinghardt to return his patients to an improved state of health and wellness, and the changes he has observed have been profound.

Klinghardt has found that 4 of 5 patients with chronic or persistent Lyme disease test highly positive for this condition (when tested with KEAC). That suggests that 80% or more of patients with symptoms of chronic Lyme disease may benefit from a treatment protocol that addresses KPU.

Klinghardt finds that it is rare for a patient to have chronic symptomatic Lyme disease as an adult without the patient having developed KPU. He postulates that the biotoxins from microbes block one or more of the eight enzymes of heme synthesis. This leads to a significant loss of key minerals in the white blood cells, which effectively disarms cellular immunity.

In those where KPU was triggered by infection with Lyme organisms, Klinghardt has observed that the KPU is often an unstable form of the condition where there are times of higher levels of pyrroles being excreted and times when this is not observed. If a person has episodes of depression, these episodes generally correlate to times when pyrroles are being released in higher levels in the urine.

One young adult female struggling with Lyme for several years had severe multiple chemical sensitivities (MCS) that were not improved by any previous treatment. After starting the KPU protocol, she noticed improvements in her MCS for the first time since she became ill. Other patients with intractable chronic infections have experienced significant improvements in immune function and a resulting lowering of total microbial burden.

Klinghardt has observed numerous patients that have struggled to rid the body of parasitic infestations. In these patients, regardless of the interventions used, the patient continues to expel these parasites on an ongoing basis. Therapy-resistant infections are a hallmark sign of KPU. Klinghardt has found that once the KPU protocol is put in place, there is often a swift resolution of long-standing infections and infestations. This includes patients who have failed years of antibiotic therapy for chronic or late-stage Lyme disease.

Sandeep Gupta, MD, from Australia has stated that parasites and pyroluria almost always go together. He has observed that almost every chronically unwell individual seems to have both; one opens the door to the other. Chronically low levels of zinc allow parasites to invade the mucosal layer of the gut. Parasites may then move to the liver and gallbladder. They interfere with mood, energy levels, and sleep. Addressing the parasites while restoring zinc and B6 often makes a tremendous difference in his patients.

Chronic Lyme disease patients often suffer from severe jawbone infections that may require cavitation surgery, which often tends to fail in this population. When the clients are pretreated for KPU, the outcome of the surgical procedure is generally much better. In some mild cases, ozone treatment of the jaw may be sufficient to turn things around.

Klinghardt has followed the interest in HLA-DR genetic typing in regards to biotoxin illnesses such as Lyme disease and mold. Prior to KPU, patients with certain haplotypes were considered more difficult to treat as the body could not properly and effectively respond to and remove biotoxins from Lyme disease, molds, or in the worst cases, both. In his experience, once the KPU issue is addressed, these HLA types become far less of a concern in most patients and no longer hold them back on their road to regaining health.

Once bodily systems are back online and functioning properly, a few months after introducing the KPU protocol, patients become less vulnerable to Lyme disease, to mold, and even to heavy metals. Their bodies are now much better equipped to deal with these conditions when they have appropriate levels of zinc, vitamin B6, biotin, manganese, and arachidonic acid to support optimal functioning of numerous bodily processes.

KPU and Methylation

In Klinghardt’s work, if a patient has KPU, treating the KPU condition first is a foundational intervention before pursuing more specific methylation support. Specific enzyme blockages are discussed earlier in this article.

In people with cancer and active EBV infection, EBV triggers a hypermethylation inside the cancer cells that may accelerate cancer cell growth. If methylation support is introduced based on genetic SNPs or other lab testing but the patient has an untreated, active EBV infection (such as is common in chronic fatigue syndrome, Lyme disease, and other related conditions) or an EBV-related cancer such as throat, stomach, breast, prostate, or Hodgkin lymphoma, supporting methylation may lead the patient to an increased risk of cancer or accelerated rate of cancer growth.

This potential makes treating KPU first even more important as balancing the zinc and B6-dependent enzymes indirectly
without the addition of methyl groups is generally a safer way to restore healthy methylation on all fronts as opposed to directly supporting methylation with methyl donors.

When people begin to explore methylation, KPU should always be evaluated and addressed first. Several enzymes in or adjacent to the methylation cycle use the heme molecule which utilize zinc and vitamin B6 as primary building blocks. By supporting KPU, the methylation cycle works more smoothly, both in its ability to methylate and demethylate, and at a lower risk to the patient.

KPU and Heavy Metal Toxicity

When KPU is present and zinc and vitamin B6 are depleted, the detoxification pathways are overwhelmed and ineffective as the heme molecule is an integral part of many detoxification enzymes. Both zinc and vitamin B6 deficiencies, which are important cofactors in the methylationcycle, reduce levels of glutathione in the body. Glutathione is important for the detoxification of heavy metals and other toxins.

Replacing missing zinc and vitamin B6 increases glutathione. This, in turn, increases the rate of detoxification of heavy metals and other body burdening
toxins. Once KPU treatment is introduced with zinc and B6, reducing the metal burden no longer requires heroic measures.

However, it is also the case that incorporating the KPU protocol will liberate additional heavy metals within the body. This aspect of the KPU protocol is discussed later in this article and is important for the practitioner to understand before beginning to treat patients for the condition as additional detoxification support is generally needed. This protocol is intended to be done only with the guidance of a knowledgeable practitioner.

KPU and Porphyrin Disorders

There is a group of disorders related to pyroluria called porphyrias. KPU is one of a group of conditions known as porphyrin diseases. In 100% of porphyrin diseases, the HPL compound is found in the urine.

Porphyrin testing is readily available and is a reliable tool. Klinghardt prefers to send a urine sample to Laboratorie Philippe Auguste (http://labbio.net) in France for testing. Other options are also available in the US, such as through Genova Diagnostics, Doctor’s Data, and Great Plains Laboratory.

In the US, pyroluria and porphyria are viewed as separate conditions. However, in collaboration with the Dutch lab KEAC, it has been established that everyone with elevated porphyrins has pyroluria. When pyroluria is addressed, the porphyrins go down.

In porphyrin testing, uroporphyrin is an indicator for aluminum, coproporphyrin for lead, and precoproporphyrin for mercury. Klinghardt has not seen a case with elevated porphyrins that did not have KPU, and when the KPU was corrected, aluminum, lead, and mercury are excreted
from the body, and the porphyrins go down.

This is, in part, due to the fact that when the body has been deficient in zinc for a long period of time, it may retain heavy metals much more readily. When zinc is missing from the body, it is replaced in our bones with lead. If zinc is supplemented, lead is expelled. Secondly, the enzymes needed to detoxify these metals are heme-dependent enzymes,
and these metals accumulate when heme synthesis is abnormal.

Klinghardt notes that discussions on the topic of porphyria are much more widely accepted than those on pyroluria. In his experience, he finds that almost all of his patients have elevated porphyrins, and that pyroluria is the deeper core issue.

KPU and Histamine

When a KPU patient is having a good day, low histamine levels are observed; on a bad day, higher histamine levels are observed. It is the relative elevation of histamine in response to foods, inhalants, allergens, emotional stressors, and electrosmog that is problematic and causes the allergic phenomena, not the absolute histamine level. When histamine levels rise from a low level to a moderate level, the reactions are often severe. Learn how to control your histamine levels in my guide located here.

When exploring histamine levels in a KPU patient at a time when they are experiencing hives or asthma, the histamine levels are elevated, but not to levels that would create a problem for others. The relative rise in histamine, however, in KPU patients is experienced in a far more significant way.

Klinghardt has worked with biochemists in Germany that are beginning to link KPU with mastocytosis or mast cell activation syndrome (MCAS). They have observed that KPU treatment repairs the heme molecule, which notably stabilizes the mast cells and lowers the response to these relative rises in histamine.

KPU and Multiple Sclerosis

Klinghardt has treated many patients with multiple sclerosis. The MS patients that he has tested have been highly positive for KPU. Over time, he has
concluded that KPU is a frequent cofactor in MS. He has found that patients with MS respond favorably to KPU treatment.

In patients with KPU, absolute histamine levels are almost always low. The treatment for MS patients with KPU may include histamine in addition to the KPU protocol outlined in this article. Treatment with histamine may be either with oral or transdermal products. Prokarin is a transdermal patch which delivers histamine and has been used by some practitioners in the treatment of MS.

Evaluation and Testing

Klinghardt recommends that people start with the HPU Questionnaire (http://www.hputest.nl/evraag.htm). Once the questionnaire is completed, a score is calculated to provide a probability that a person may have KPU. If the score is 10-14, Klinghardt will often recommend proceeding with treatment without the need for confirmatory testing as the treatment itself is generally well-tolerated.

If the score is 0-9, he may suggest testing for the condition using additional lab work.

Pyrroles are impacted by light, temperature, oxygen, and time; and they readily break down. Once they begin to break down, the likelihood of detection is significantly lowered. Ideally, testing would be performed within eight hours after the collection, though this is not practical and rarely possible.

Within the United States, two of the available labs for testing include the following:

  • DHA Laboratory (https://www.pyroluriatesting.com) uses a frozen one-time collection at a cost of $80. They recommend the collection be the second urination of the day. They suggest avoiding all supplements, vitamins, and minerals for 12-24 hours prior to the specimen collection. The lab is testing for hydroxyhemopyrrolin-2-one (HPL).
  • Health Diagnostics and Research Institute (http://www.hdri-usa.com) charges $140 for a 24-hour collection and $90 for a random collection. HDRI suggests stopping zinc and B6 as well as antidepressant medications for 48 hours prior to the collection. They suggest not smoking or consuming caffeine for 24 hours prior. While there is no additional cost for testing the hydroxyhemopyrrolin-2-one (HPL) compound, this must be specifically ordered on the requisition form as it is not part of their KPU assay by default. If you do not specify HPL as an add-on, you will get kryptopyrrole (2,4 dimethyl-3-ethyl pyrrole) only.
  • In Europe, Klinghardt uses the Dutch Lab KEAC (http://hputest.nl) for HPU testing. The lab is guided by microbiologist Dr. John Kamsteeg, a world leader in HPU. The results of HPU testing with this lab align closely with the percentages of patients with chronic Lyme and other conditions that Klinghardt identifies with the HPU condition.
  • In Australia, KPU testing is available through SAFE Analytical Laboratories (http://safelabs.com.au) and Applied Analytical Laboratories Pty Ltd (http://www.apanlabs.com).

Each lab has their own very specific instructions for performing the test. This includes information such as shielding the specimen from light as well as how to handle and ship the specimen. It is important that the recommendations be closely followed to optimize the sensitivity of the test result.

To further maximize the sensitivity of testing, it may be best for the patient to be under stress at the time the test is being performed as HPL excretion is known to increase during times of stress.

In some circumstances, however, patients may still test negative even when the condition is suspected. In those cases, it may be best to repeat the test. In many cases, the result will be positive on the second or third test. In some patients, an empiric trial of the KPU protocol may be indicated despite repeated negative KPU tests, and this often leads the patient to
higher ground. WBC (not RBC) intracellular zinc may be a useful tool for exploring the potential for zinc deficiency where it matters most – in the white blood cells.

Other laboratory indicators that may be suggestive of KPU include the following:

  • WBC < 5000/mcL (due to low levels of zinc)
  • High LDL / Low HDL
  • Low normal alkaline phosphatase (<60U/L)
  • Low omega-6 fatty acids in red cell membrane test
  • Low taurine in amino acid profile
  • High MCV
  • Low glutathione
  • Low ATP
  • WBC and RBC zinc and manganese levels may be normal while biopsies from bone and CNS are completely deficient.
  • Bone biopsies are a reliable predictor of KPU. Severe deficiencies of zinc, manganese, lithium, calcium, magnesium, and molybdenum are often found.

Alkaline phosphatase (ALP) is a zinc and magnesium dependent enzyme. When someone is consuming adequate magnesium and is still presenting with low ALP, zinc deficiency is a likely consideration, and this may represent another indication for KPU. When ALP is below 55, zinc deficiency can be suspected; when below 40, it is likely.

A consequence of KPU is low glutathione and low ATP. In the realm of chronic illnesses, low reduced glutathione and low ATP are common and should alone trigger the suspicion that KPU may be a factor.

Treatment

KPU is a severe but reversible deficiency of zinc, vitamin B6 (or P5P), biotin, manganese, arachidonic acid, and other co-factors. It is important to recognize, however, that treatment with zinc and vitamin B6 does not result in fewer pyrroles being excreted in the urine. KPU orthomolecular treatment does not fix the underlying condition; it substitutes what is being lost as a result of the condition such that the person is no longer deficient in key nutrients needed by the body to move towards health.

The general KPU substitution treatment that Klinghardt uses in his practice is as follows (dosages for 160 lb.) adult and should be adjusted based on weight; may be customized for specific patient needs):

With Breakfast

  • Zinc 25-30 mg (as picolinate, gluconate,sulfate, or zinc l-carnosine). Nausea after zinc supplementation may be a sign of hypochlorhydria or low stomach acid; this often resolves after a few months on treatment.
  • Vitamin B6 50-100 mg (split between pyridoxine HCl and P5P, with P5P being the predominant form)
  • Biotin 3-5 mg for brain, skin, hair, and nails
  • Magnesium 100 mg (glycinate, bisglycinate, or malate) – or titrate to bowel tolerance.
  • Arachidonic acid from omega-6 oils (Ghee such as Mt. Capra Goat Milk Ghee, Evening Primrose Oil, Hemp Seed Oil, Black Currant Oil, Borage Oil, Pumpkin Seed Oil; 4-6 capsules of Evening Primrose Oil per day is commonly used.)

With Dinner

  • Zinc 25-30 mg
  • Vitamin B6 50-100 mg
  • Biotin 3-5 mg
  • Magnesium 100 mg
  • Omega-6 Oils

This is the core treatment Klinghardt utilizes for KPU.

Additional Support

  • Vitamin A 1,500-3,000 IU per day to improve the absorption of zinc in the gut
  • Niacin 40-50 mg per day for psychiatric symptoms. (Abram Hoffer used up to 3000 mg per day.)
  • Taurine 100 mg twice per day (up to 2,000 mg at bedtime) for brain-related symptoms such as seizures, brain fog, and memory loss. Supports elimination of neurotoxins, improves bile quality, increases glutathione, and normalize brain rhythms.
  • Lithium 5-10 mg per day (Orotate or Aspartate); lithium is lost in the urine in some patients with KPU.
  • Manganese 2-5 mg per day (Patients with joint problems may require additional manganese above the dosages recommended here; see additional considerations later in this article on manganese for patients with Lyme disease.)
  • Chromium 250-500 mcg per day
  • Molybdenum 100-500 mcg per day
  • Boron 1-3 mg per day
  • Trace Minerals – As more is learned about KPU, additional elements are found to be lower in those with the condition. Thus, supplementing trace minerals may be a supportive strategy. BioPure MicroMinerals, Quinton Isotonic, or similar mineral products may be helpful

As compared to the first version of this article which was published in 2009, Klinghardt has found that many of hispatients do quite well with lower dosagesof some of these key nutrients than were originally utilized.

In Europe, Depyrrol is one product which provides support for KPU. Additionally, and in the United States, BioPure CORE and CORE-S are available to support those dealing with the condition. Another product in this realm is Mensah Medical’s Pyrrole Pak. These products serve as a solid foundation for KPU treatment; though additional co- factors may be needed for a given patient.

Some patients may not tolerate both vitamin B6 and P5P as contained in some products and may find it necessary to take each component of the KPU program separately.

In terms of BioPure’s CORE and CORE-S, CORE-S is a recent reformulation of the CORE product which has been available for many years. While either may be an appropriate option, CORE-S generally results in less nausea, better absorption, and is often better tolerated by those patients with Lyme disease as it does not contain manganese. While many with pyroluria may benefit from manganese, it may act as a growth factor for untreated Lyme disease, and thus, some may prefer to avoid its use in this patient population. The reformulated CORE-S contains horsetail as people with KPU excrete higher levels of silica in the urine, which leads to higher levels of aluminum toxicity. With either CORE or CORE-S, two capsules twice daily are a common target dose for a 160 lb. adult.

When first starting to introduce products in support of KPU, it is best to start with lower dosages and to take them towards the end of a meal and to gradually work up to the target dosage. Levels of B6, taurine, or biotin may be additionally and individually titrated upwards depending on the patient’s symptoms and needs. With the introduction of zinc, it is best to monitor copper levels after a few months on the protocol as copper replacement may also be needed. Zinc, vitamin B6, and manganese are copper antagonists. Thus, monitoring levels of copper and supplementing where needed is an important part of the treatment protocol.

Copper deficiency can lead to hemorrhoids, varicose veins, fatigue, edema, hair loss, anorexia, skin problems, osteoporosis, cardiovascular disease, aneurisms, and many other undesired conditions. Current nutritional teachings are misinformed on the topic of copper toxicity. The immune system uses copper and iron to fight infections associated with Lyme disease. As a result, oxidized copper is displaced in the connective tissue and may appear as though the patient is copper toxic by some testing methods when in fact copper supplementation may be appropriate. High dose Vitamin C has the effect of reducing oxidized copper to a form that can be reused by the body.

Detoxification and Course of Treatment

As treatment for KPU is implemented, this often can result in toxin mobilization as the body begins to release heavy metals. Symptoms may include muscle aches, bowel problems, or those normally associated with cleansing or detoxification reactions. Additionally, the immune system begins to become more active which can result in a Herxheimer-like reaction as the immune system begins to better respond to the backlog of microbes that it was previously unable to adequately address.

One approach for minimizing these reactions is to start slowly with introduction of the KPU nutrients and work up over time. In most cases, there is no reason that the treatment course must be an aggressive one. Nonetheless, this treatment should always be guided by a knowledgeable practitioner. In addition to the KPU treatment discussed earlier, consideration should be given to detoxification support and to protection of the red blood cells as the treatment is initiated.

According to Klinghardt, many of our metabolic enzymes use zinc as part of their molecular makeup. However, in patients with KPU, there is not enough zinc available to satisfy the need. In these cases, lead, mercury, and other 2-valent metals bind to these sites instead in a poor attempt to fulfill the role of zinc.

Once zinc is reintroduced into the body, 2-valent metals such as mercury, cadmium, aluminum, and lead are liberated. The patient may now have dislodged heavy metals circulating throughout the body.

These may be competing for the already overtaxed detoxification pathways or may be redistributed to places where they may be more problematic. Lead moves back into the blood, which can cause problems including damage to red blood cells. To protect the red blood cells, freeze-dried garlic and Vitamin E are often used.

Incorporation of known toxin binders further supports the detoxification process. Some of the binders that Klinghardt uses in his practice include chlorella, Ecklonia cava, zeolite, and
chitosan. Silica from horsetail supports binding of aluminum, and thus, the use of a high-silica zeolite such as BioPure ZeoBind is often utilized. It is critical to support the kidneys with specific drainage and organ support remedies in order to optimize the removal of heavy metals and to avoid stressing the kidneys.

An interesting observation has been that patients with KPU often get worse when an attempt is made to incorporate detoxification agents or antimicrobial agents prior to having first addressed the KPU condition. Once KPU has been addressed, other treatment options are often much more effective and better tolerated.

Additional Considerations

Many patients with chronic Lyme disease have issues with sulfur intolerance. This leads to a patient being unable to effectively utilize a number of detoxification agents such as alpha-lipoic acid, DMSA, DMPS, and glutathione; as well as supplements such as garlic. This may be related to genetic predisposition, but some of the enzymes involved in sulfur metabolism (CBS and others) are heme and B6 dependent; both of which are depleted in KPU. As patients are treated for KPU, these sulfur tolerance issues may resolve. Klinghardt has found that molybdenum at a dose of 100-500 mcg per day may correct sulfur intolerance in patients with KPU, as molybdenum may also be lost in these patients.

Ammonia is generally high in patients with KPU. As KPU is treated, high levels of ammonia tend to normalize. To bind and excrete ammonia, zeolite may be used.

Resolution of KPU

For most with the condition, supplementation will be required for life. However, Klinghardt has seen complete resolution of the condition after having addressed epigenetic influences, trauma, or unresolved conflicts using tools such as mental field therapy, family constellation work, or EMDR. By resolving trauma in the ancestry, the epigenetics are influenced in a positive way and the condition resolves.

Klinghardt has also observed complete resolution of Lyme-induced KPU when the infection is managed successfully with biological interventions.

Final Thoughts

Once patients are on the KPU protocol and mobilized metals have been addressed, the body begins to respond to backlogged infections and significant improvements in the patient’s condition
are often observed. Hormonal status often improves. Some patients who have been on thyroid medication for years may even become hyperthyroid as the body begins to function more optimally. Other patients may lose weight. Symptoms directly related to low levels of zinc, vitamin B6, biotin, manganese, and arachidonic acid often resolve.

Just as homes are built by first laying a solid foundation, addressing KPU and the deficiencies in zinc, vitamin B6, biotin, manganese, and arachidonic acid are key pieces of the puzzle in addressing the complexities of chronic Lyme disease and many other conditions.

Evaluation for KPU is one of the first things that Klinghardt pursues in working with patients with chronic illnesses. Implementing the KPU protocol often yields progress that had not previously been possible, and patient recovery is accelerated in a very deep and profound way.

Disclaimer

This article is not intended to provide personalized treatment recommendations or to facilitate self-treatment. Treatment should be done only under the care and supervision of a licensed medical authority. Attempts to self-treat the condition may result in unintended negative consequences.

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Scott Forsgren, FDN-P, is the founder of BetterHealthGuy.com, a health coach, blogger, podcaster, health writer, advocate, support group facilitator, and LymeLight Foundation board member. He recovered his own health after a 20-year journey through Lyme disease and mold illness. Today, Scott is grateful for his current state of health and all that he has learned on this life-changing journey. Dr. Klinghardt served as a powerful mentor, teacher, and guide as Scott worked to understand the disease which had previously taken so much of his life and moved toward a place of health and wellness. Scott continues to utilize a maintenance pyroluria protocol which he started almost a decade ago. To follow Scott’s work, visit http://www.betterhealthguy.com. His podcast “BetterHealthGuy Blogcasts” is available on his web site and on YouTube, iTunes, Google Play, and Stitcher.

Dietrich Klinghardt, MD, PhD, studied medicine and psychology in Freiburg, Germany, completing his PhD on the involvement of the autonomic nervous system in autoimmune disorders. Early in his career, he became interested in the sequelae of chronic toxicity (especially lead, mercury, environmental pollutants, and electromagnetic fields) and its impact on chronic illness. Dr. Klinghardt has contributed significantly to the understanding of metal toxicity and its connection with chronic infections, illness, and pain. He has developed Autonomic Response Testing, a comprehensive evaluation system that has helped many practitioners to become accomplished holistic practitioners. He founded Sophia Health Institute (http://www.sophiaha.com) in 2012, and is actively involved in patient care at his clinic outside of Seattle. More information on his educational seminars can be found through the Klinghardt Academy (http://www.klinghardtacademy.com; US) and the Klinghardt Institute (http://www.klinghardtinstitute.com; UK).[/vc_column_text][vc_empty_space][vc_row_inner][vc_column_inner width=”1/2″][dt_default_button bg_hover_color=”#dd3333″ border_radius=”6px” border_width=”0px” button_padding=”12px 18px 11px 18px” default_btn_bg_color=”#1e73be” font_size=”16″ icon=”JTNDaSUyMGNsYXNzJTNEJTIyZmElMjBmYS1maWxlLXBkZi1vJTIyJTIwYXJpYS1oaWRkZW4lM0QlMjJ0cnVlJTIyJTNFJTNDJTJGaSUzRQ==” icon_size=”16″ link=”url:http%3A%2F%2Fhoofa.wpengine.com%2Fwp-content%2Fuploads%2F2017%2F08%2FKryptopyrroluria-aka-Hemopyrrollacramuria.pdf||target:%20_blank|” size=”custom” text_color=”#ffffff” text_hover_color=”#ffffff”]Download PDF of this Article[/dt_default_button][/vc_column_inner][vc_column_inner width=”1/2″][/vc_column_inner][/vc_row_inner][/vc_column][/vc_row]

Limitations of Traditional Medicine – Observation Two: It distorts the doctor/patient relationship

In our last post, we discussed how most diagnoses don’t just fall innocently out the sky at some point in life’s trajectory and how easy it is, once a diagnosis has been made, for patients to objectify the diagnosis as something separate from themselves, the choices they have made and the life they have lived. This process of objectification of illness has been disparagingly called N2D2 medicine; the name of disease = name of the drug. Dr. Sydney Baker has termed it “name it, blame it. tame it” medicine.

This trend in modern medicine has a further interesting effect on the relationship between the doctor and the patient. By avoiding cause and effect inquiry, it limits the patient’s involvement in their own care and projects the power to heal onto some outer authority. The doctor is seen as all healthy; the patient is often seen as all sick. The patient frequently identifies with their diagnosis in order to derive some form of identity and meaning from this one-sided relationship. It is a means of barter and exchange within the allopathic system.

The implication is that when this transaction occurs, and the patient assumes the illness as an immutable, fixed, objective entity of sorts, the patient’s “inner physician” completely shuts down. Their desire for self-enquiry and self-advocacy for bringing all that it takes for themselves to heal their illness, closes off as the responsibility gets shifted onto the outer authority figure, whether it be a doctor, naturopath, psychologist or some other member of the healing profession.

This occurrence is particularly tragic because it has been my observation that it is the physician within the patient that needs to be activated to result in a true transformation. The inner physician’s healing action is as great as that of the physical doctor/healer appearing on the external scene. Similarly, if the inner healer is not activated by the conscious act of intention by the patient, the possibility of a true healing experience is somewhat dissipated. If nothing shifts in the internal dialogue and the mental field of the patient, if the patient is not fully engaged in cause and effect inquiry and totally committed to changing previous outcomes, then the possibility of something shifting at the level of the physiology is somewhat muted and no true, lasting transformation occurs.

For example, an herb is somewhat inert unless the individual consciously links the physical substance to their intentional mental field, engages their mind in a solution-focused way, and then in some mysterious alchemical process, activates its healing potential. This process is incredibly important to the doctor/healer and patient transaction. It has been much maligned in the traditional research as exerting the so-called “placebo effect,” but if the mind-body connection is real (and the evidence is too overwhelming to ignore), then why do we not factor this into the healing equation and give credit where credit is due? If, as a patient, one is not mentally engaged and in agreement with the outlined therapeutic interventions, it is highly likely that the healing effect will be significantly compromised.