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

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

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

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

Symptoms of overactive mast cells may include:

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

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

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

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

 

Low MSH and Mast Cell Disorders?

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

 

Definition of Mast Cell Activation Syndrome (MCAS)

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

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

Diseases Associated with Mast Cell Activation Syndrome (MCAS)

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

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

Lab Tests for Mast Cell Activation Syndrome (MCAS)

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

 

Treatments to reduce MCAS symptoms and lower histamine

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

Specific Symptom Treatment in MCAS

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

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

References

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

6 Signs that SIBO might be the root cause of your IBS

Photo courtesy of www.freedigitalphotos.net

Studies show that over 50% of patients diagnosed with IBS actually have an underlying imbalance called SIBO, or small intestinal bacterial overgrowth. The majority of our gut bacteria should be in the colon. When the bacteria migrate backwards into the small bowel or when there is low stomach acid or poor pancreatic enzyme production, bacteria in the small bowel can overgrow and cause symptoms, such as diarrhea, gas, or bloating.

Six signs you might have SIBO

1. You notice that fiber worsens your constipation
2. You notice an improvement in IBS symptoms when taking antibiotics
3. You feel more gas and bloating when you take probiotics that contain prebiotics
4. You are celiac or gluten intolerant and do not have 100% resolution of symptoms on a gluten-free diet
5. You develop chronic symptoms of gas, bloating, constipation or diarrhea after taking pain medications, like opiates.
6. Your blood work shows chronically low iron or ferratin with no known cause

Top 6 Symptoms of SIBO

1. Abdominal bloating and distention
2. Constipation 
3. Diarrhea
4. Abdominal pain or discomfort
5.  Acid reflux or heartburn
6. Excessive gas or belching

How do I know this isn’t just leaky gut?

While SIBO usually manifests with local GI symptoms, a leaky gut will manifest with systemic complaints that affect the immune system. Keep in mind that is is not uncommon to have both SIBO and leaky gut simultaneously. And very often if you have SIBO for a long period of time, you will develop a leaky gut.

Here are some systemic signs of a leaky gut:

• Multiple food sensitivities
• Skin rashes, acne or rosacea
• Respiratory symptoms, like asthma
• Allergic symptoms or increase in seasonal allergies
• Fatigue
• Brain fog or poor concentration, especially after meals
• Any autoimmune disease
• Joint pain or arthritis
• Headaches or migraines

Remember SIBO can cause leaky gut syndrome but not everyone with SIBO has leaky gut. About half of the patients diagnosed with SIBO will also have leaky gut. Most of the time if SIBO is treated, leaky gut will heal itself!

10 conditions that may predispose you to have SIBO

1. Hypochlorhydria (low stomach acid)
2. Pancreatic insufficiency
3. Decreased motility in small intestine
4. Bowel obstruction
5. Diverticula 
6. Surgical bowel resection or bariatric surgery 
7. Food poisoning (Post infectious IBS)
8. Nerve damage that affects the GI tract
9. Drugs, like opiates 
10. Any disease that slows motility (diabetes, hypothyroid)

Other disorders that may be associated with SIBO

• Rheumatoid arthritis
• Ankylosing spondylitis
• Scleroderma
• Hashimoto’s thyroiditis
• Rosacea
• Restless leg syndrome
• Pancreatic insufficiency
• Liver disease
• Diabetes
• Crohn’s disease
• Celiac disease
• Fibromyalgia
• Kidney failure
• Liver disease
• Diverticulosis

How to Diagnose SIBO

Ask your doctor to order the Lactulose Breath Test (preferred over glucose as it will test the entire small bowel vs. just duodenum). You may also need to check a comprehensive stool analysis and urinary organic acids, which may point in the direction of other dysbiosis but are not directly assessing small bowel bacterial overgrowth

How do we treat SIBO?

1. Diet options

• Paleo diet or autoimmune paleo diet
• Low FODMAP diet
• Specific Carbohydrate Diet
• GAPS Diet
• Avoid all alcohol
• Use caution with probiotics/prebiotics
• Use caution with fermented foods as they can increase histamine
• Homemade Elemental Diet by Dr. Siebecker

2. Antibiotics

• Xifaxan

3. Dr. Jill’s favorite antimicrobial herbs

• Allimed
• Oil of oregano
• Thorne Berberine 500
• Biocidin 

Treating SIBO successfully is not always easy and may involve major dietary changes and medication or herbal treatment for an extended period of time. However, getting the balance of your gut microbes healthy will likely prove to be the most important step in regaining your health and vitality! I know it was in my case… if you haven't read My Story, read more here.

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Health Tips for Anyone with a MTHFR Gene Mutation...

If you haven't seen the popular blog on MTHFR Gene Mutations... What's the big deal about Methylation?, you might want to start by familiarizing yourself with this common genetic mutation that can affect everything from depression and anxiety to risk of heart attack or stroke.

In light of the amount of questions and comments I've gotten, it's about time I write a follow-up blog giving you some helpful hints in dealing with this common genetic SNP that can affect your health in so many various ways.

A little background to bring you up to speed on methylation...

First, I suggest going back to re-read the previous blog article before moving on. For a quick review.... let's define methylation.  Methylation is the act of a carbon and three hydrogens (namely a methyl group) attaching itself to an enzyme in your body. When this methyl group attaches to an enzyme, the enzyme performs a specific action. One thing you might not realize is that methylation is responsible for is the breakdown of histamine. A methyl group is made and then floats around until it finds a specific binding site. In this case, the methyl group binds to histamine. When a methyl group binds to histamine, histamine breaks apart and goes away.   Many patients who have one or more methylation SNPs, like MTHFR have a hard time breaking down histamine, which can wreak havoc on the body in many ways!

If you haven't been tested and want to find out if you have this common genetic mutation, you can ask your doctor to order MTHFR gene mutation testing through LabCorp.   Better yet you can order a genetic profile directly without a physician order online through 23andMe for only $99.

Key functions these donated methyl group are:

• Protecting DNA and RNA.  If DNA is not protected it is susceptible to damage by viruses, bacteria, heavy metals, solvents and other environmental toxins. Over time if this damage becomes significant and could even result in cancer.
• Reducing histamine levels (see this article)  Sometimes the common methyl-donor, SAMe can help reduce histamine levels.
• Protecting cell membranes.    The methyl group donated by SAMe helps build phosphatidylcholine which then gets incorporated into the walls of all your cells.  If these cell membranes become damaged and weak, the cells become fragile and harmful things may enter the cell.  If they are unable to carry in useful nutrients, they will die. Excessive cell membrane damage can lead to serious medical conditions, such as multiple sclerosis.

What are some things I can do if I have the MTHFR gene mutation?

Here's ten tips for you!

1. Avoid taking folic acid blocking or depleting drugs, such as birth control pills or Methyltrexate
2. Avoid taking proton pump inhibitors, like Prilosec or Prevacid or antacids, like Tums, which may block essential Vitamin B12 absorption
3. Have your homocysteine measured, which if elevated may indicate a problem with methylation or a deficiency of B12 or folate.  If your homocysteine is elevated, limit your intake of methionine-rich foods
4. Avoid eating processed foods, many of which have added synthetic folic acid.  Instead eat whole foods with no added chemicals or preservatives.
5. Get your daily intake of leafy greens, like spinach, kale, swiss chard or arugula, which are loaded with natural levels of folate that your body can more easily process.
6. Eat hormone-free, grass-fed beef, organic pastured butter or ghee, and eggs from free-range, non-GMO fed chickens.  
7. Remove any mercury amalgams with a trained biologic dentist.  Avoid aluminum exposure in antiperspirants or cookware.  Avoiding heavy metal or other toxic exposure is important.
8. Make sure you supplementing with essential nutrients, like methyl-B12, methyl-folate, TMG, N-acetylcysteine, riboflavin, curcumin, fish oil, Vitamins C, D, E, and probiotics.  If you are double homozygous for MTHFR mutations, you should proceed very cautiously with methyl-B12 and methyl-folate supplementation as some people do not tolerate high doses.  Introduce nutrients one by one and watching for any adverse reactions.  Use extreme caution when supplementing with niacin, which can dampen methylation.
9. Make time for gentle detox regimens several times per week.  These could include infared sauna, epsom salt baths, dry skin brushing, and regular exercise or sweating.
10. If you have a known genetic mutation, share the information with parents, children and other family members and encourage them to be tested, too!  The easiest way is to order  through 23andMe for only $99 online.

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What's the Big Deal about Methylation?! Update of the popular MTHFR blog post...

UPDATE OF POPULAR MTHFR BLOG POST

Do you have a genetic defect in the MTHFR gene??

Maybe you've have a family history of heart attack or stroke... maybe you've suffered through multiple miscarriages.  Or maybe you struggle with chronic migraine headaches or irritible bowel syndrome or depression.  Perhaps your child or a sibling has autism.  What do all these things have in common?  Well, these are just some of the conditions liked to a faulty enzyme called MTHFR.

What's up with MTHFR?

MTHFR stands for methyl-tetrahydrofolate reductase, an enzyme that is responsible for the process of methylation in every cell in your body.  MTHFR is a common genetic variant that causes this key enzyme in the body to function at a lower than normal rate.  This can lead to a variety of medical problems.  Although there are over fifty known MTHFR variants, the two primary ones are called C677T and A1298.  Your doctor can order a blood test to determine if you have these genetic variants. Better yet, you can order a complete genetic profile yourself through 23andMe.

What's the big deal about methylation?

Methylation is a core process that occurs in all cells to help your body make biochemical conversions.  When people with genetic mutations is MTHFR are exposed to toxins, they have a harder time getting rid of them which can cause some very serious illnesses.  The methylation process is responsible for:

• Cellular Repair: synthesis of nucleic acids, production and repair of DNA and mRNA
• Detoxification and Neurotransmistter  Production:  interconversion of amino acids
• Healthy Immune System Function:  formation and maturation of red blood cells, white blood cells & platelet production

The 677T variant is most commonly associated  with early heart disease and stroke and the 1298C variant with a variety chronic illnesses, but either anomaly can cause a wide variety of health problems.  The MTHFR anomaly is reported out as heterozygous or homozygous.  If you are heterozygous that means you have one affected gene and one normal gene.  Your enzyme activity will run at about 60% efficiency compared to a normal.

If you are homozygous or have 2 abnormal copies, then enzyme efficiency drops down to 10% to 20% of normal, which can be very serious.   The worst combination is 677T/1298C in which you are heterozygous to both anomalies.  Many chronic illnesses are linked to this anomaly.   Fibromyalgia, irritable bowel syndrome, migraines, chemical sensitivity, frequent miscarriage and frequent blood clots are all conditions associated with MTHFR anomaly.  For a great diagram of more methylation related health problems, check this out:

MTHFR Related Health Problems 

Glutathione is the body's primary antioxidant and detoxifier.  One of the ways that MTHFR gene mutation can make you susceptible to illness is by lowering your ability to make glutathione.    People with MTHFR anomalies usually have low glutathione, which makes them more susceptible to stress and less tolerant to toxic exposures.  Accumulation of toxins in the body and increased oxidative stress, which also leads to premature aging.

Some conditions that may be associated with MTHFR gene mutations

• Autism
• Addictions: smoking, drugs, alcohol
• Down’s syndrome
• Frequent miscarriages
• Male and female infertility
• Pulmonary embolism and other blood clots
• Depression and anxiety
• Schizophrenia
• Bipolar disorder
• Fibromyalgia
• Chronic Fatigue Syndrome
• Chemical Sensitivity
• Parkinson’s disease
• Irritable Bowel Syndrome  
• Stroke
• Spina bifida
• Migraines
• Hyperhomocysteinemia
• Breast cancer
• Atherosclerosis
• Alzheimer’s
• Multiple Sclerosis
• Myocardial Infarction (Heart Attack)
• Methotrexate Toxicity
• Nitrous Oxide Toxicity

 

Treatment for MTHFR

Fortunately, you can easily be tested for the MTHFR mutation.  If you find out that you have one or more of the gene mutations, you can supplement with methyl-folate  and methyl B12, the active forms of these B vitamins.   You can also supplement with liposomal or acetyl-glutathione, the end product of the pathway.  Glutathione is poorly absorbed so either the liposomal form or a precursor, called n-acetylcysteine (NAC) may be used. Some of my favorites are Thorne Research Methyl Guard Plus and 5-MTHF 1mg and 5mg.

There are prescription medicines, that also contain methyl-folate: Deplin, MetanX, CerefolinNAC are a few.   Methyl B12 can also be given as shots, nasal sprays, and sublingually.  The intramuscular shots are by far the most effective method and must be prescribed by your physician.  The choice of nutrients will vary from patient to patient and should be done under a doctor's supervision.  There is a bell-shaped optimal curve so you may not feel well with too much or too little of the appropriate supplements.   Other B vitamins, such as riboflavin and vitamin B6 also play an important role.  As you may have surmised, this can be quite complex and I suggest you find a functional medicine trained physician to help you sort through your needs for the different nutrients if you have a chronic health condition related to the gene mutations.  It is not uncommon for patients with these genetic polymorphism's to be very sensitive to supplementation.

Patients who I recommend be screened for MTHFR mutations:

• Mood disorders: depression, anxiety, irritability, mood swings, bipolar
• Infants and children of parents with MTHFR mutations
• Family members related to someone with MTHFR mutations
• Infertility and Pre-conception care: test both man and woman
• Elevated folate (not processing to active 5-MTHF due to inability to methylate)
• Elevated homocysteine (due to low active 5-MTHF and methylcobalamin)
• Elevated s-adenosylhomocysteine (due to low active 5-MTHF and methylcobalamin)
• Elevated serum cobalamin (due to inability to methylate cyanocobalamin to methylcobalamin)
• Elevated methylmalonic acid (due to methylcobalamin deficiency)
• Patients with syndromes: IBS, multiple chemical sensitivity, fibromyalgia, Down syndrome, chronic fatigue syndrome
• Neurological disorders: Multiple sclerosis, Autism, Alzheimer’s, Epilepsy, Parkinson's
• Cancer: family history of cancer or undergoing cancer treatment
• Cervical dysplasia
• Cardiovascular risk: family history of strokes, embolisms, heart attacks, clots, hypertension
• Birth defects: cleft palate, tetralogy of Fallot, spinal bifida, midline defects
• Drug sensitivities: methotrexate, anti-seizure meds, nitrous oxide, anesthesia

If you are interested in knowing more about your genes, the 23andme gene test will be the best $99 investment you've ever spent !

Check out Health Tips for Dealing with MTHFR Gene mutations...

More reading

23andMe Gene Test
Holistic Primary Care 
Genetics Home Reference
Molecular Biology of MTHFR
Genetics of Homocysteine Metabolism
Homocysteine and MTHFR mutation
LiveWello Gene app

MTHFR gene mutation... What's the big deal about Methylation?

UPDATE POST OF MTHFR BLOG

Do you have a genetic defect in the MTHFR gene??

Maybe you've have a family history of heart attack or stroke... maybe you've suffered through multiple miscarriages.  Or maybe you struggle with chronic migraine headaches or irritible bowel syndrome or depression.  Perhaps your child or a sibling has autism.  What do all these things have in common?  Well, these are just some of the conditions liked to a faulty enzyme called MTHFR.

What's up with MTHFR?

MTHFR stands for methyl-tetrahydrofolate reductase, an enzyme that is responsible for the process of methylation in every cell in your body.  MTHFR is a common genetic variant that causes this key enzyme in the body to function at a lower than normal rate.  This can lead to a variety of medical problems.  Although there are over fifty known MTHFR variants, the two primary ones are called C677T and A1298.  Your doctor can order a blood test to determine if you have these genetic variants. Better yet, you can order a complete genetic profile yourself through 23andMe.

What's the big deal about methylation?

Methylation is a core process that occurs in all cells to help your body make biochemical conversions.  When people with genetic mutations is MTHFR are exposed to toxins, they have a harder time getting rid of them which can cause some very serious illnesses.  The methylation process is responsible for:

• Cellular Repair: synthesis of nucleic acids, production & repair of DNA & mRNA
• Detoxification and Neurotransmistter  Production:  interconversion of amino acids
• Healthy Immune System Function:  formation & maturation of red blood cells, white blood cells & platelet production

The 677T variant is most commonly associated  with early heart disease and stroke and the 1298C variant with a variety chronic illnesses, but either anomaly can cause a wide variety of health problems.  The MTHFR anomaly is reported out as heterozygous or homozygous.  If you are heterozygous that means you have one affected gene and one normal gene.  Your enzyme activity will run at about 60% efficiency compared to a normal. 

If you are homozygous or have 2 abnormal copies, then enzyme efficiency drops down to 10% to 20% of normal, which can be very serious.   The worst combination is 677T/1298C in which you are heterozygous to both anomalies.  Many chronic illnesses are linked to this anomaly.   Fibromyalgia, irritable bowel syndrome, migraines, chemical sensitivity, frequent miscarriage and frequent blood clots are all conditions associated with MTHFR anomaly.  For a great diagram of more methylation related health problems, check this out: 

MTHFR Related Health Problems 

Glutathione is the body's primary antioxidant and detoxifier.  One of the ways that MTHFR gene mutation can make you susceptible to illness is by lowering your ability to make glutathione.    People with MTHFR anomalies usually have low glutathione, which makes them more susceptible to stress and less tolerant to toxic exposures.  Accumulation of toxins in the body and increased oxidative stress, which also leads to premature aging.

Some conditions that may be associated with MTHFR gene mutations

• Autism
• Addictions: smoking, drugs, alcohol
• Down’s syndrome
• Frequent miscarriages
• Male & female infertility
• Pulmonary embolism and other blood clots
• Depression & anxiety
• Schizophrenia
• Bipolar disorder
• Fibromyalgia
• Chronic Fatigue Syndrome
• Chemical Sensitivity
• Parkinson’s disease
• Irritable Bowel Syndrome  
• Stroke
• Spina bifida
• Migraines
• Hyperhomocysteinemia
• Breast cancer
• Atherosclerosis
• Alzheimer’s
• Multiple Sclerosis
• Myocardial Infarction (Heart Attack)
• Methotrexate Toxicity
• Nitrous Oxide Toxicity

 

Treatment for MTHFR

Fortunately, you can easily be tested for the MTHFR mutation.  If you find out that you have one or more of the gene mutations, you can supplement with methyl-folate  and methyl B12, the active forms of these B vitamins.   You can also supplement with liposomal or acetyl-glutathione, the end product of the pathway.  Glutathione is poorly absorbed so either the liposomal form or a precursor, called n-acetylcysteine (NAC) may be used. Some of my favorites are Thorne Research Methyl Guard Plus and 5-MTHF 1mg and 5mg.

There are prescription medicines, that also contain methyl-folate: Deplin, MetanX, CerefolinNAC are a few.   Methyl B12 can also be given as shots, nasal sprays, and sublingually.  The intramuscular shots are by far the most effective method and must be prescribed by your physician.  The choice of nutrients will vary from patient to patient and should be done under a doctor's supervision.  There is a bell-shaped optimal curve so you may not feel well with too much or too little of the appropriate supplements.   Other B vitamins, such as riboflavin and vitamin B6 also play an important role.  As you may have surmised, this can be quite complex and I suggest you find a functional medicine trained physician to help you sort through your needs for the different nutrients if you have a chronic health condition related to the gene mutations.  It is not uncommon for patients with these genetic polymorphism's to be very sensitive to supplementation.

Patients who I recommend screen for MTHFR mutations:

• Pre-conception care: test both man and woman
• Mental dysfunction including but not limited to depression, anxiety, irritability, mood swings, schizophrenia, bipolar
• Infants and children of parents with MTHFR mutations
• Family members related to someone with MTHFR mutations
• Elevated folate (not processing to active 5-MTHF due to inability to methylate)
• Elevated homocysteine (due to low active 5-MTHF and methylcobalamin)
• Elevated s-adenosylhomocysteine (due to low active 5-MTHF and methylcobalamin)
• Elevated serum cobalamin (due to inability to methylate cyanocobalamin to methylcobalamin)
• Elevated methylmalonic acid (due to methylcobalamin deficiency)
• Patients with syndromes: IBS, Chemical sensitivity, Fibromyalgia, Down Syndrome, Chronic fatigue syndrome
• Neurological disorders: Multiple sclerosis, Autism, Alzheimer’s, Epilepsy, Parkinson’s to name a few
• Cancer: family history of cancer or undergoing cancer treatment
• Cervical dysplasia
• Infertility
• Cardiovascular risk: family history of strokes, embolisms, heart attacks, clots, essential hypertension
• Birth defects: cleft palate, tetralogy of Fallot, spinal bifida, midline defects
• Drug sensitivities: methotrexate, anti-epileptics, nitrous oxide, anesthesia

If you are interested in knowing more about your genes, the 23andme gene test will be the best $99 investment you've ever spent !

Check out Health Tips for Dealing with MTHFR Gene Mutations...

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For more reading

Holistic Primary Care 
Genetics Home Reference
Molecular Biology of MTHFR
Genetics of Homocysteine Metabolism
Homocysteine and MTHFR mutation
23andMe Gene Test