Methylation Dysfunction

Methylation Dysfunction

Since several afibbers have tested positive for the polymorphism or gene mutation, MTHFR, which tracks to methylation dysfunction, I thought it would be helpful to post notes from an interview on the topic of Methylation Dysfunction, causes and treatment precautions, especially because many of the signs and symptoms of methylation dysfunction are both common and highly recognizable. That’s not to say that testing isn’t a good idea.

INTRO – THE SHORT VERSION
• Gene flaws or mutations such as MTHFR are fairly common and cause methylation dysfunction which manifests in a large number of ailments that are not typically recognized as coming from that source.
• Genetic expression of known gene flaws can often be controlled or prevented through nutritional interventions, lifestyle and environmental changes.
• Diagnosing and treating methylation dysfunction can be challenging and requires the skill and knowledge of a seasoned practitioner who has significant experience in this field since patients can become severely ill when treatment is too aggressive or not fully understood by the practitioner.

Most everyone is familiar with the term, “trickle-down effect”…. and Methylation Dysfunction is a classic example because one thing leads to so many others in a long complicated chain of associations.

INTRODUCTION - METHYLATION DYSFUNCTION
Many afibbers have other health issues with symptoms commonly associated with methylation dysfunction so this overview should be useful… especially for those with severe anxiety, mood disorders, insomnia, food sensitivities and more. My ears perked up when I heard that often those with methylation defects are intolerant to nutritional supplements – which reminded me of Fran Ross who absolutely could not tolerate any supplements and was prone to seizures and afib.

Often, when methylation dysfunction is mentioned, we tend to think automatically of elevated blood levels of homocysteine as causal and that’s that. While homocysteine elevation is a cardinal marker of a potentially harmful amino acid, there are multiple causes for its elevation. And, homocysteine can also be too low.

The most significant and extremely important reason for concern over elevated homocysteine is that it is found to cause atherosclerosis and cardiovascular problems. As the following list indicates, methylation dysfunction and elevated homocysteine cause many serious ailments. Prevention is the key for elevated homocysteine rather than reversal of atherosclerosis once established.

Although MTHFR and other polymorphisms affecting proper methylation function are fairly common, without specific testing or diagnostic knowledge by practitioners about MD as an underlying cause, the mutations are not routinely traced back as the source of a patient’s ill health when they “express” and patients feel unwell. Typically patients are treated with multiple drugs that help to mask the symptoms but have not addressed the etiology or core cause.

Intolerance to nutritional supplements, certain foods or sensitivities to environmental exposure such as perfumes or scents, exhaust and petroleum fumes and chemical odors, EMFs, GMOs pesticides/ herbicides are common signs of methylation dysfunction in a long list of associated conditions
.
Gene mutations affecting methylation dysfunction are known to be present on average in about one in every two people and underlie most health ailments and diseases. Testing for mutations can be very helpful but almost not needed (at least initially) because the symptoms of methylation dysfunction are such predictable indicators that serve to plot a treatment plan by an expert in the field.

Methylation dysfunction, polymorphisms and elevated homocysteine is a perfect example of the importance of knowing about “epigenetics.” As noted, genetic mutations that allow for methylation dysfunction are relatively common, (one in every two people on average) – yet not all those people have methylation dysfunction because they get from diet enough of the key nutrients needed in the cycle to prevent the expression (or manifestation) of the genetic mutation. As mentioned in many previous posts on genetic expression (Epigenetics), just because the gene mutation is present, “you don’t have to be held hostage to your genetics.” [Lipton].

Aside: This also applies to genetic mutations that set some of us up for the arrhythmia manifestation (or expression)--yet not others. The challenge is determining which polymorphism affects what and applying that knowledge as prevention.

It’s established that there is a polymorphism for magnesium absorption and utilization.[References: A missense mutation in the Kv1.1 voltage-gated potassium channel–encoding gene. 2009]

As one example, when methylation cycle requisite nutrients are in place and the resultant enzymatic reactions are working, homocysteine levels are normal. But genetic mutations and other interferences in the cycle can run interference and cause other problems. That’s what makes it so complicated. Key nutrients that can be deficient in elevated homocysteine include folate (folic acid), vitamin B12, vitamin B6, riboflavin, trimethylglycine (betaine), methionine and various other enzymes; or, there can be renal insufficiency, the MTHFR or the other polymorphisms or certain drugs interfere as well. Methylation dysfunction is of concern to everyone. It’s obviously useful to make sure you test for fasting serum HCY so you know your level as either too low or too high can cause multiple health complications.

Since this topic is so extensive and complex, my intention is just to highlight important tips to motivate readers to do independent research. Reference links to experts highly knowledgeable on this topic are provided. Be aware that while some practitioners think they are experts, many are not even close. Patients can have significant adverse reactions to methylation treatment so this serves as an alert to be cautious and choose an experienced practitioner.

Those who are strict vegans and vegetarians will find the information on elevated homocysteine as a result of low vitamin B12 and methionine important.

We’ve mentioned methylation and B vitamins in many posts over the years. Long ago, when our resident MD, Patrick Chambers, was participating, he offered posts indicating that AF was beriberi of the heart--deficiency in thiamine or vitamin B1. In 2004, Methylation was the topic of Conference Room 20. Other threads can be reviewed by using the search feature for All Forums, All Dates and using the word Epigenetics.

Following are a few of Dr. Lynch’s observational highlights and treatment precautions to serve as an alert because during the interview, it became clear that treatment can be tricky and often causes patients to become more ill. Some end up in the ER. It’s definitely not a DIY project.

Be aware this interview was presented to medical practitioners. The treatment and dosing discussed is based on his experiences treating severely ill patients.

As mentioned initially, this is a huge, complex topic involving extensive research. My notes presented in this overview are not to be considered comprehensive and should not in any way be considered instructions diagnose or treat yourself. Rather, they serve to inform that methylation dysfunction is a significant underlying factor behind many, many health ailments and until that is addressed; improvements in health may be elusive. Specific forms of supplemental nutrients and dosing protocols are required.

A good subtitle for this report might be The Iceberg Phenomena because the scope and complexities of methylation dysfunction are so hugely broad with deep and far-reaching interconnections that it’s impossible to corral all the details in a not-so- brief summary. More discoveries occur continually. Underlying all is the most significant connection – Epigenetics-- which makes Methylation Dysfunction a classic example. Hopefully, these few nuggets will be useful to many readers who will investigate further with a well- qualified practitioner.

As I always say, Knowledge is Power.

Jackie


Homocysteine
Homocysteine (HCY) is a sulfur-containing amino acid and an inflammatory compound formed by abnormal protein metabolism and is controlled to maintain normal or safe levels by the methylation cycle. When homocysteine accumulates to toxic levels, various health consequences result but quite often, since homocysteine isn’t routinely tested, the health impact continues to compound. Patients may have to insist on testing and pay out of pocket. It’s worth it.

The elevation of HCY is a very complex matter with over100 different factors that are demonstrated to lead to elevation. There are over 200 different alleles of three basic enzymes in the heterozygous enzymatic disorder leading to elevation of homocysteine that are described in the last decade or so that lead to increased risk. [McCully]

Elevated HCY is shown to be the cause of atherosclerosis as a result of fibrosis (there’s that word again) causing inelasticity of arterial walls because of the body’s inability to methylate or process amino acids properly due to lack of certain enzymes and critical vitamins. The type of atherosclerosis homocysteine produces is of the fibrous type but without lipid deposition. [McCully]

Elevated HCY and Methylation Dysfunction is known to contribute to – partial list:
• increased tendency to form unwanted blood clots (homocysteine is one of the important risk factors of thick, sticky blood
• cerebrovascular disease (stroke)
• heart attacks
• arrhythmia
• vascular damage
• aneurysms
• plaque buildup
• cardiovascular disease including (heart attack)
• peripheral vascular disease (gangrene),
• kidney failure
• alterations in DNA
• adult neurological conditions
• development of certain cancers
• thyroid dysfunction
• brain excitation, mood, depression and neuropsychiatric disorders
• seizures, panic attacks, rages
• migraines
• addictions, alcoholism
• chronic fatigue/fibromyalgia syndromes
• decreased energy, decreased muscle tone
• insomnia, restless leg syndrome
• through DNA alterations, autoimmune disorders including thyroiditis, Graves disease, pernicious anemia, Lupus, gout, rheumatism, rheumatoid arthritis, Down syndrome, Multiple Sclerosis, ADD, ADHD, Huntington's disease, Parkinson's
• diabetes
• impotence
• autism and other spectrum disorders
• fertility problems; miscarriages, spina bifida, cleft palate and neural tube defects
• acid reflux
• sensitivity to sulfites, sulfur-containing foods
• poor memory
• 200% higher risk of developing dementia and 211% increased risk for Alzheimer’s due to specific B vitamin deficiency and elevated HCY
• aging
• (even death).

Previous posts on homocysteine highlighted books by Kilmer S. McCully, MD and Craig Cooney, PhD, which serve abundantly well to explain in depth the complications of methylation and how it relates to our health. Now, with everything right at our fingertips via the Internet, several excellent web informational sources are also listed in the reference section. It’s worth knowing the background of Dr. McCully’s discovery story as he found so many years ago that homocysteine is the cause of atherosclerosis rather than cholesterol. Dr. McCully is referred to as the father of the homocysteine theory of cardiovascular disease and his important story and struggle to bring the concept of this significant health risk factor to light against the tide of medical orthodoxy deserves the spotlight in any discussion on homocysteine or methylation. [See Reference details]

A Life Extension report deserves a read because the bright side of the McCully story is that justice (and science) prevailed and 30 years later, Dr. McCully has been vindicated and is now praised for his foresight and dedication to finding the connection between aberrations in homocysteine levels and cardiovascular disease which led to other important findings as well. It was a long time coming.

The LEF report proclaims: Thirty years ago colleagues scoffed at his idea that homocysteine causes heart disease. New data proves McCully was right all along. See also Dr. McCully’s bio link in References…more than impressive.

Homocysteine levels can also be too low and cause other medical problems. See End Notes by Cardiologist, Stephen Sinatra which is supported by Dr. Lynch in his as well.

Of relevance to afibbers is this study published in Am Heart J Sept 2004 titled:

Hyperhomocysteinemia and vitamin B6 deficiency: new risk markers for nonvalvular atrial fibrillation?
Conclusions: This study demonstrates a significant association of both elevated Hcy levels and low vitamin B6 levels with the presence of NVAF; in addition, it confirms the role of Hcy as a risk factor for ischemic events during NVAF. PMID: 15389232

(But there’s so much more than a low B6 level to consider. Even the specific form of B6 is important.)

The Interview – Methylation Do’s and Don’ts
Benjamin Lynch ND 3/17/13
The two-hour interview on Methylation Dysfunction was with Naturopathic Physician, Benjamin Lynch, who has devoted his career to learning about and practicing Environmental and Nutrigenomic (Epigenetic) medicine. Dr. Lynch narrowed that to a focus on Methylation Dysfunctions and the related genetic polymorphisms that occur in more of the population than is generally recognized by most clinicians. He spoke on the complications of methylation dysfunction and what is currently known about treatment options along with caveats on treatment protocols that can cause patients to “flare” with dire consequences.

Dr. Lynch explained the influences of genetic variations or polymorphisms called SNPs (pronounced ‘snips’) on proper function of the methylation cycle or pathways; one being the MTHFR mutation (methylene-tetrahydrofolate reductase). The field of SNPs and Epigenetics is huge, complicated and widely misunderstood when attempting to treat patients who test positive.

Dr. Lynch received a BS in cellular and molecular biology from U of Washington and his ND from Bastyr University. His passion for identifying the cause of disease directed him to Nutrigenomics, Environmental Medicine and Methylation Dysfunciton. Currently, he researches, writes and presents nation-wide on the topic of MTHFR and Methylation defects. He is president and CEO of Seeking Health, a company oriented toward disease prevention and health promotion and no longer sees patients. See his website for more details. [References]

Experts in the field of methylation agree that
….”Methylation is involved in almost every bodily biochemical reaction and occurs billions of times every second in our cells. That’s why figuring out where the Cycle can better perform its tasks contributes to health improvement and reduces symptoms.” [Amy Yasko, PhD]

What you need to know:
The methylation pathway or cycle is better explained while looking at a cycle chart to understand the flow and interactions leading to various end-results. There is a cycle link in the references and hopefully, this report highlights key points to alert readers to symptoms or lab results that may go unaddressed such as:
• Other systems affected by methylation dysfunction
• Symptoms of methylation cycle dysfunction
• Why those with the MTHFR or other SNPs may find they react adversely to aggressive treatment or to various environmental exposures including dietary supplements and some foods ie, sulfur containing.

Methylation is critical. It affects every aspect of the patient’s health and plays a role in
• Detoxification
• Immune function
• Maintaining DNA
• Energy production
• Mood balancing
• Controlling inflammation

What is Methylation?
• Methylation is defined as replacing a hydrogen atom with a methyl group.
• A methyl group contains 3 carbon atoms and 1 hydrogen atom.
• To undergo or cause a chemical reaction in which a methyl group is introduced into a molecule

The methylation cycle is described as a simple chemical process in a complicated, interactive pathway with other systems. The process involves transferring (attaching) a methyl group to other molecules that regulate a myriad of vital functions…including cognitive, neuroendocrine, immune system function, detoxification, cardiovascular health and numerous others.

Methylation is one step in the all-important Phase II liver detoxification pathway (conjugation pathway) where liver cells add a molecule to a toxic substance to make it less harmful and enable it to be excreted via bile or urine. Methylation dysfunction adds considerably to detoxification complications and people can become very ill when they don’t have proper liver clearance…especially if that is not resolved before treating.

The body uses this methylation process to assist in removal of its own chemical wastes such as hormone by-products, dangerous heavy metal toxins or other environmental toxins such as pesticides.

…. “Methylation controls genetic expression (DNA) by silencing the bad ones and allowing the good ones to be “read.” In the aging process, it stabilizes telomere segments by protecting from oxidation and helps to turn on telomerase, the only safe, natural way to lengthen telomeres.” [Immortality Edge]

The methylation of phospholipids primarily affects the lipid bi-layers of cell membranes and plays a critical role of in the structure and function of cell membranes - especially important for afibbers.

Abnormal methylation is influenced by age and ethnicity and is substantially inhibited by factors that increase oxidative stress such as smoking, infections, inflammation, exposure to radiation and environmental toxins. It’s not at all uncommon for people to have genetic flaws as we are all mutants as we evolved as a species. Some ethnic groups are more prone than others, but on average, it’s reasonable to say that one in every two people have genetic polymorphisms so it’s important to recognize that fact and treat patients properly. But not all methylation dysfunctions are the result of SNPs but rather from the environmental influences mentioned.

Integrative Cardiologist, James Roberts describes methylation this way:
“ The Methyl Cycle is the backbone of our physiology. Its functional status determines our resistance or susceptibility to environmental toxins and microbes. This is a confusing array of biochemistry, but suffice it to say, a defect at any one point in these interlocking cycles will inevitably affect the remaining pathways, and your overall health will then suffer. Methyl Cycle abnormalities explain why you are sick from environmental toxins while the guy next door is just fine, why you are autistic while your fraternal twin brother is not. While we cannot change your DNA, if we know your weak links we can create "nutritional workarounds" - we can supplement alternative pathways or withhold from your diet molecules that you cannot handle. If we do not address the Methyl Cycle abnormalities that underlie unexplained or chronic illness, well then- the illnesses will remain chronic and unexplained, because it is the Methyl Cycle Abnormalities that predisposed you to ill health.
Individuals with Methyl Cycle Defects are the “canaries” of our society. Toxins will hurt all of us eventually but those of us with Methyl Cycle Defects will be the first to go down.” [Reference URLs (Roberts)]

(If you have symptoms of methylation dysfunction or a known polymorphism, I suggest you go to both websites of Dr. Lynch and Dr. Roberts [References] and start reading so that you are prepared to understand the complications of treating for this problem)

Interview Highlights of interest

Patient Assessment – it’s complicated.
When Dr. Lynch worked in the Bastyr clinic in Environmental Medicine, he saw that 60%of people get better and 40% got worse with standard protocols…so he is very anti standard treatment protocols because they don’t work and you can’t write protocols for every variant of MTHFR (methylene-tetrahydrofolate reductase). The two most common defects found in the MTHFR mutation are the C677T and A1298C alleles.

For any patient who walks through your door, do the basic naturopathic and functional evaluation protocols and automatically think: Environment, Diet, Lifestyle Behaviors, Psyche of the patient, Gut Healing and Methylation prior to starting on any protocols for methylation because you must reduce the burden before you make the body deal by beefing up the methylation cycle. Assess and Address. If you don’t, you can’t solve the problem.

Much can be determined from the initial interview and asking questions. Symptoms often surface, such as the headaches with odors. Common symptoms include (just a few of many)
Addictions – large number
Mood disorders – big one
Depression
Anxiety
Anger
Irritability
Brain Fog
Insomnia
Nerve problems

If things don’t improve during treatment, you can offer to run the 23andMe test to determine if various genetic polymorphisms are present so you can deal with them appropriately. But keep in mind there are cautions and ethical considerations when running the 23andMe test since often, people are not able to handle knowledge of the results. (23andMe analyzes hundreds of thousands of SNPs scattered across 23 pairs of chromosomes that make up the human genetic sequence.)

So, first remove the causes— could be mold in the home, chemicals at work, EMFs, foods or many other factors. If I give methylcobalamin to one patient who did really well but another was unresponsive or didn’t even aggravate them…why might that be?
1) didn’t absorb
2) poor quality supplement
3) have carrier protein deficiencies; ie trans-cobalamin proteins deficiencies.

You have to be able to carry (transport) the B12 (methylcobalamin) for it to work. May not have enough folate on board so if you gave B12 but it’s not doing anything, maybe they need methyl folate to help the methionine cycle start working – These two work as a duo.

There can be a problem converting methylcobalamin into adenosyl cobalamin. About 25% of people have a limited ability to convert. People who feel that energy burst when they take B12…part is the conversion to adenosyl cobalamin which is essential to our mitochondrial energy and the mitochondria use that form of B12 specifically-- so that’s one aspect.

With folic acid, the body has to convert through at least 4 different steps folic acid – which is synthetic - to a more usable form -- tetrahydrofolate by dihydrofolate reductase and it is a very slow process. You can burden someone with that or if they have a mutation or SNP in the upstream folate metabolism, they are not going to get much response. In the case of pregnancy, the baby won’t develop very well as methylation is needed for DNA production.

It’s complicated, but someone who doesn’t have gene defects can take synthetic folic acid and be fine. Others, if you gave folate as methylfolate, they may find their depression lifted; but another, given 1 mg began having seizures or became severely agitated. This is because other enzymes in the body can be inhibited either through lack of methylation or inhibition from vaccines, toxins, bacteria, heavy metals, lack of other co-factors, mineral and vitamins or there can be other SNPs namely COMT that slows the breakdown of epinephrine and norepinephrine and serotonin…so they could have a serotonin storm which we all know is bad news. Optimal methylation is required for neurotransmitters dopamine and serotonin to convert down to norepinephrine and epinephrine.

We could spend a whole hour talking about variants with just these two nutrients. This is just one example of how important it is to be aware of and understand the nuances.

Everyone has some type of dysfunctional methylation – whether or not it is significant or outwardly obvious, there is always something that can be improved. As an example-- SAMe is a required nutrient – need 3 SAMe’s to make carnitine and that’s only the first part of the pathway. Carnitine is extremely difficult to produce so a lot of MDs focus on mitochondrial dysfunction which is great, but if you just focus on that and give carnitine, alpha lipoic acid, CoQ10, ribose and so on, you possibly miss the bigger upstream picture and that is methylation. Mitochondrial dysfunction is a big problem – many diseases are a result of that.

Research shows that SAMe has been looked at as a potential to developing cancer --depends on the form of cancer…some caused by over methylation and some, under-methylation.

Folic Acid vs natural folate
It’s important to recognize the bad press on Folic Acid and Cancer was on the synthetic form of folic acid and not the natural folate form. Reliable supplement companies have reformulated to use only the natural folate but others continue to include the less expensive folic acid form. Be aware.

Folic acid fortification in food products was mandated years ago in the US, Canada and Mexico. Other countries have grappled with the similar mandates mostly as preventive for neural tube defects but with synthetic folic acid being added to so many common foods, the likelihood of getting too much can be high. In people with adequate liver clearance, that doesn’t seem to cause problems. However, the liver has a limited capacity to metabolize or reduce folic acid so significant quantities of unmetabolized folic acid enters systemic circulation and has the potential to cause adverse health effects associated with cognitive decline, cancer, multiple births and immune function.
[See References on 2007 Summary Report on the Folic Acid Controversy]

Vegan/Vegetarian diets and vitamin B 12 deficiencies
Dr. Lynch mentions that vegans and vegetarians tend to be deficient in B12. In another interview with Dr. McCully, he elaborated more on this.
Vegan/Vegetarian diets avoid meat or anything containing a decent amount of amino acids. Vegans have higher HCY levels, according to a German study, mainly because of a deficiency of vitamin B12 since that’s mainly in food of animal origin. Soy protein has a deleterious effect which is well documented. Soybeans are totally devoid of B122 and can increase the body’s requirements for B12 and can raise homocysteine levels.

Vegetarians almost exclusively eat soy protein so we can assume both B12 and methionine deficiency and will have elevated homocysteine levels as a result.

Sufficient B12 is found in meat, seafood, some dairy products including milk and eggs.

In 2008, Dr. McCully signed a petition to the FDA by Weston Price Foundation to rescind the health disease claims allowed on soy products. The claims are not sustained by the scientific literature. Soy and soy protein, isoflavones and other soy constituents are risk factors including elevated homocysteine and thyroid function, fertility and digestion. Soy protein has multiple toxic effects not taken into account by the FDA when allowing the claims. Soy protein has been demonstrated to be atherogenic in monkey experiments and over a period of months, monkeys were found to be deficient in methionine. (As of 2010, the petition to remove false health claims had not been acted upon.)
It’s not just soy, but a protein intake deficiency. Johns Hopkins and NIH in ’97 (?) found elevated HCY in those with restricted protein intake. The lower the protein – the higher the HCY. Adequate protein intake with methionine is needed to prevent hyperhomocysteinemia in animals and humans.

In the monkey project, they added cholesterol to the soy protein diet and the monkeys developed plaques but if they gave additional methionine, the plasma levels of cholesterol and plaques disappeared. Soy protein has been demonstrated to be atherogenic in monkey experiments.
B12 deficiencies are also caused by aging and the decline in stomach lining ability to produce hydrochloric acid which is needed to absorb B12. Drugs lower stomach acid secretion. Those at higher risk for low stomach acid and B12 deficiency are those over 45, vegans or vegetarians, have digestive problem, low stomach acid, anemia, consume alcohol, take acid-blocking medications or certain diabetes drugs including metformin.

So… then the downstream effect impacts methylation and that whole broad spectrum cycle.

Supplement forms
Folate – L-5-MTHF… the natural folate or Nature folate is preferred to eliminate the need for the body to do the four conversions of folic acid to folate. Designated on the label as L-5-methyltetrahydrafolate

B12 – in the form of methylcobalamin…rather than cyanocobalamin

B6 – in the form of Pyridoxal 5’ Phosphate…pronounced… five prime phosphate. This form eliminates the need to convert B6 to the natural active form.

Vitamin B2 – Riboflavin - is found to be important in those with the genetic variant of MTHFR, 677TT as these people require optimal riboflavin and folate for normal enzymatic activity to prevent elevated HCY. Riboflavin is also needed for B6 metabolism to make it active.

TMG – trimethylglycine…uses a different pathway (betaine transmethylase) which is present in the liver only.

Molybdenum – brief mention- he finds some are deficient in Mo and respond well to adding that.

Sometimes it’s necessary to add serine and methionine.

Cancer
Treating those with cancer is tricky. Cancer occurs with under-methylation for so long you now have turned on genes that should not be and turned off other genes that should be left on. DNA methylation turns on and off cancer prevention genes; i.e., p56 needs to stay on.

Question: When to do you order labs for the SNPs testing? We need to know if you have MTHRF; is there a COMT issue so that the supplements impact methylation if there are defects.

Answer: Important question and I leave that up to the individual. I don’t run a lot of tests because I am very focused on history which gives a large amount of clues to guide treatment. After the first office call, we have more than enough to work on.

If we aren’t making progress in whatever time frame goals are set by the patient-- like in 3 months I want to be completely well, and the patient is better, but now we’re stuck and can’t change lifestyle or add more nutrients, the basic labs aren’t improving, then I am open to bring up the genetic testing. I explain to them and be very clear that genetic testing has a very important ethical consideration especially 23andMe tests because 23andMe is not a treatment-oriented test. It’s not built for that but many doctors, including myself, use it to guide treatment. Personally, I’d like to run the 23andMe test on every patient so the information is there and available because it can speed treatment.

The problem is, it can scare patients as it indicates if the patient is susceptible to serious diseases and it can be very disturbing to patients. Example- .some surgeons run breast cancer genetic testing for the BRCA gene and if that comes back positive for BRCA, women are running to get radical mastectomies. That’s just the gene test. If it has a SNP or variant or is mutated or is absent or what have you, that does not mean it is a problem. Just because you have that genetic change, from the wild-type normal gene doesn’t mean it’s an issue…so you can have genetic problems even if the gene is normal. You can have inhibition through organophosphates, xenobiotics, hormones, co-factor deficiencies and so on so the short answer to your question is.. I personally like to run it from the beginning but I would have some type of video or paper that the patient can take home to study and then decide if they want to run the test . They really need to be educated on what may happen if they get the test back with positive markers.

One of my patents was anxious his whole life. We did the test and even though he was prepared ahead of time, but when he found out he had the snips that prevent conversion of glutamine to GABA and snips that prevent the breakdown from norepinephrine to epinephrine, he freaked out.. .but I put him on B’s and B6, zinc, magnesium, Ashwaganda and GABA and he calmed right down in about 30 minutes. But the benefit of the testing is now we know why he has been so anxious his whole life and he’s thankful for that but at the same time, it freaked him out even though I did prepare him and educate him but it can be hard to prepare some individuals for the results. We should test but ethically really emphasize the risks involved.

Q. Someone could have no SNPs and it could just be lack of substrates or environmental exposure and other factors so what should clinicians first start with? Do you start by loading up the patient on methylation factors and see how it goes? Some practitioners do that. They give high dose folic acid, B 12, SAMe – what are the benefits and risk of just doing high dosing?

A. The benefit is you might get lucky and have the happiest patients of your life and then get a whole bunch of referrals… or the risks are you may flare them and get a lot of lost referrals and you could also send them to the ER. Thankfully, I’ve never sent anyone to the ER. But I have definitely affected kids and adults for the worse by giving them headaches, depression, insomnia, increased irritability – not an emergency but definitely not pleasant.

My approach is to introduce one nutrient at a time. Keep it simple

I’d choose methylcobalamin (B12) to start with because if you give just methylfolate first and in high dose, and if you don’t have enough cobalamin, you’ll trap the methylfolate. Use your best judgment based on their symptoms. Start with cofactors first.

If they have neurological problems I’d probably focus on methylcobalamin first.

If they have mitochondrial dysfunction, I’d start with acetyl l carnitine first; . not B12.

For elevated HCY –and generally normal person in terms of sensitivity, I would also ask if the person is sensitive to supplements and if so, then definitely introduce only one at a time small dose and don’t do any other changes for several days before introducing the next nutrient.

If they are robust and supplements don’t affect them but HCY is elevated, then try a combo supplement Folate, B12, B6, Betaine, TMG, B2 and they should be fine.

Just to clarify…Dr. Lynch says he is treating the sickest of the sick in his practice so following his dosing recommendations is not the best for the standard population. Generally if they tolerate 10 or 15 different supplements before beginning his treatment, they are okay with the higher doses he uses… but each case is different and you have to proceed with caution.

Methylation is produced constantly in our system and at times you need more because you burn through your neurotransmitters and eating up the methyl groups…compared to lying on the beach relaxing.

Take away statement…Everyone needs methylation support. To find the cause of disease, you need to look at methylation and to do so you need the tools and awareness of how to improve methylation safely and effectively. The field is growing rapidly.

If you are a practitioner who is just starting to treat methylation, it’s important to work with other experienced practitioners, but there aren’t that many. Amy Yasko is where I started learning but the problem with the Yasko protocol is (in his opinion) nothing is cited or referenced and he has a problem with that. He uses and wants to see references so people can verify the information.

Practitioners must learn the cycles of methionine, folate, transsulfuration and learn all you can about glutathione metabolism, glutathione transfer factors, promoters and inhibitors. Apply toward everyone. Start low and work up. Read more about it. Review the MTHFR.net website info. The final pages have the protocols he recommends to physicians.

Q&A Segment – abbreviated.

Q. When patients “flare” as a result of treatment? …

A. Use niacin or sodium bicarbonate or potassium bicarbonate right away to neutralize the effect.
Niacin has saved countless people from the side effects of excessive methylfolate and SAMe and the reason it works is because in order to get rid of niacin from the body, it requires SAMe.

So if you get a side effect several weeks after they are doing fine but then they crash, just stop all the methylation supplements and give niacin and tell them to hang on.

I like to use nicotinic acid because I want to see if they flush or not; otherwise you can use niacinamide - I typically recommend 50 mg to a130 mg every 30 minutes until their symptoms are gone – symptoms can be a crazy ballistic kid who’s breaking windows in the car. I didn’t induce that - .another doc did, but I recommended 50 mg of nicotinic acid and within 30 minutes the kid completely calmed down and was fine. I start low and work up.

Important point– say you do flare your patient.- or they start getting irritable, or have headaches and you give the niacin - once you achieve that point with the nicotinic acid. where they are doing well… then you’re done. Repeat: You are done.

And you might want to lower the methylcobalamin/methylfolate or skip a day or two I tell my clients if you are feeling good today when you wake up – don’t touch your methylfolate or the methylcobalamin. If you have no tingling, you’re clear headed, in a good mood – you leave it alone. You don’t want to make it worse and then have to come back by starting the whole process again…that’s a real hassle. I’ve seen it time and time again.

Note well - Methylation supplements are not to be used on a daily basis… use in a time of need and then back off. This is not like a multi vitamin or fish oil or vitamin D or C that you take on a daily basis. These things work fast and they are very effective - treat with respect and you will get amazing results with your patients. Just have your niacin on hand.

Q. Folate testing?
A. Folate in labs is the whole caboodle of folate….not a specific folate. So you don’t know what her methylate folate level is. A good lab for methylfolate would be Health Diagnostics. [References] With MTHFR you can see elevated folate and elevated B12…so again lab testing doesn’t show that much and you have to go by symptoms. So for a C677 individual if they are not eating a bunch of uncooked leafy greens and not sensitive to supplements, I would start on a combo of methylcobalamin and methyl folate. And an HCY of 8 is not that elevated…but keep in mind what are they eating-- are they eating enough protein? If they are not eating that much protein then their homocysteine is not going to be that high. Are they low in glutathione because most of the homocysteine is actually going down through the transsulfuration pathway and being utilized to try to produce glutathione rather than producing SAMe and everything else?

So homocysteine is not just metabolized by methyl folate and methylcobalamin – it is also metabolized by vitamin B 6 in the Pyridoxal-5'-phosphate (P5P) form and betaine (TMG) so that’s important to understand and we also need to know that a lot of people who don’t eat enough protein can be low in homocysteine just from that. So low homocysteine is as bad or even worse than high homocysteine….in my opinion.

Q Do the GMO’s, water fluoridation, high levels of mercury and other toxic metals interfere with methylation?

A. Absolutely. One theory of why these are so bad is when GM foods are produced, the bacteria used to make the gene insertion into the food are also imbedded into the food so you eat a lot of odd bugs in the GM food and our immune system attacks them…causing an up-regulation of the immune response which produces inflammation and everything else. So then, your immune system tries to attack that bug in the GM food… but since it’s in the food, you become allergic to the food but your body is trying to attack the bacteria. That’s the theory. It makes total sense if it’s really true.

This is why you start with the basic changes first -- lifestyle, diet, environmental factors, behavioral psyche.

The end of the video on the MTHFR.net website…talks about the MTHFR in Italy. where it’s 50% of the population and the whole reason the US decided to enrich our foods with folic acid is because of neural tube defects. So now we have folic acid in all our foods, prenatals and everywhere. If you look in America at the MTHFR, they correlate with neural tube defects. If you have MTHFR in America, you have neural tube defects--.directly correlated. In Italy, they are not correlated. Why? At the time of the study, they did not enrich their foods with folic acid and they don’t have neural defects… leading me to believe it is our environment, lifestyle and diet.

I think the reason these SNPs or mutations are becoming expressed is the environment and the burden on us from these constant exposures – fast-paced lifestyles with EMFs and everything else, GMOs, pesticides, herbicides that are causing these mutations. I think MTHFR mutations have been around a long, long time but our environment is triggering the expressions of it.

Dr. Lynch refers to an on-line video presentation at his MTHFR.net website. Details for detecting and treating methylation defects including the MTHFR gene aberration can be found at [www.seekinghealth.com] a 45 page pdf presentation on this topic.

Dr. Lynch cautions that when treating patients with nutritional support requires caution so they don’t have adverse reactions such as Herxheimer’s response (page 37) – often called “flares.”

Side Effects to Look For When Starting Methylfolate Meds or Supplements
•Muscle Pain
•Irritability
•Anxiety
•Depression
•Joint Pain
•Nausea
•Headache
•Insomnia
•Seizures
•Vomiting
•Stomach Pain
•Sweating
•‘Herxheimer Reaction’ (Flare)
•Rash
•Palpitations

Page 40 indicates reactions to or intolerance to both supportive nutrients such as Methylfolate and Methylcobalamin and page 41 offers list of Do’s and Don’ts for dosing…which many beginning practitioners don’t realize and patients become severely reactive and ill.

End of interview


Endnotes

One thing not mentioned in the interview which I recall reading somewhere in previous research is that once methylation gets functioning properly, it has a tendency to lower potassium levels so beware if you are actively treating for methylation defects, be sure your potassium intake is optimal.

In 2004, Methylation was the topic of CR 20 [www.afibbers.org]
And Molybdenum in 2003 [www.afibbers.org]

Regarding Desired or Safe levels of Homocysteine… Dr. McCully responded in his February 2008 interview, that generally, fasting levels of 6 to 8 millimoles/liter are associated with a low risk of vascular disease. Levels of 15 are associated with greater risk. The higher the level for HCY, the higher the risk.

In older men with levels about 12 and higher – the risk increases significantly. Post menopausal women are also at higher risk. He emphasized that prevention was the key rather than trying to reverse with vitamins… although in several studies with post-stroke patients put on the appropriate high diet regimen did have a lower incidence of recurrent stroke after a four-year treatment period.

Notes from an interview (4/20/11) on Electropollution with Integrative Cardiologist, Stephen Sinatra in which he gives his views on Methylation issues.
He was asked a question about homocysteine since he commented one reason his son became so ill from electropollution was because he couldn’t methylate. Previously in The Red Flags post, Dr. Sinatra’s recommendations from his 2001 newsletter were:
Cardiologist, Stephen Sinatra says “Generally, “normal” for homocysteine is anything between 5 and 15 micromoles per liter, but epidemiological evidence suggests that optimal levels are less than 8 mm/l. Population studies in the Mediterranean Basin (France and Spain) have low mortality from cardiovascular disease, with levels averaging 7 –8 mm/l. In countries with high mortality rates (Finland, Scotland, Northern Ireland, Germany) homocysteine levels average 10 – 11 mm/l. He considers anything above 9 to be dangerous.” (Sinatra Health Report 3/01)

Ten years have passed and Dr. Sinatra now offers more refinement regarding where homocysteine levels should be and why.
A caller questioned if it was safe to have HCY levels up to 10 rather than the typical requirement of low to a high mid-7.

Sinatra response:
The reason being is people think homocysteine is like cholesterol…you want it lower and lower … but people who have HCY around 7 have an over-expression of Cystathionine synthase which means they are metabolizing HCY at a rapid rate which means when they are doing that there is a block in their methylation pathway. People with low HCY around 7, 6 or 5 have an over-expression of sulfate and sulfite in the urine and this is as bad as people with HCY of 11, 12, 13 and 14 and 15.

Homocysteine has a sweet spot. And lower is not necessarily better.

Q. So even up to 10 is okay?
A. Yes… I used to think 7 – 9 was really ideal, but if I had a 10 HCY, that doesn’t really ruffle my feathers much. Would I put them on tetrahydrofolate or folic acid or folinic acid or B12 and B6? – Sure. But it wouldn’t concern me like a HCY of 20 or 21 or a HCY of 5. It’s all relative.

When it comes to HCY, you’ve got to start at an early age. Women who take BC pills and who develop coronary artery disease in their 30’s and 40’s after 20 years of BC pills, have a deficiency of B vitamins B6, B12, folic acid. BC pills cause that.

[Additional observation… since BC pills deplete B’s, it’s important for women who take the pill for a number of years to supplement heavily prior to planning a pregnancy in order to lower the risks of birth defects including spina bifida.]

If you treat someone who is 60 yrs old with a HCY of 17, you aren’t going to do anything for these people. I would still treat it because of the Alzheimer’s and inflammation factor but it isn’t going to make a difference with coronary disease.

The time to treat HCY is with 17-year olds - male and female. The younger the better because it takes years for the endothelial dysfunction to cause free radical stress damage in the arteries.

Q. In terms of raising it if it’s too low?
A. I don’t think you need to raise it but when it’s too low you need to be aware that you are over-expressing an enzyme that is increasing the turnover of HCY so for these people, I’d tell them to avoid sulfites. Dried fruits, wine, garlic, garlic, asparagus, eggs…Physicians should be aware of methylation pathways. My son, Steph, was convinced one of the reasons why he could not reverse his toxicity was because he had a problem with the COMPT pathway along with an over expression of Cystathionine-synthase so he was building up sulfites and the problem with COMPT as well. So you have to know how these biochemical pathways are involved in the equation because the environment is so much more toxic than it was 50 years ago. One of the reasons he got so sick was because he couldn’t methylate.

Q. In people who have problems metabolizing sulfur…nutritionists asks the question: People say after eating asparagus, my urine smells strange. So is this the problem with sulfur coming out in the urine?
A. Yes, that could be the poor-man’s methylation test. Some people can have that reaction the next morning after eating asparagus; other people can have it in two hours after eating and that could be a tip-off that they might have an over-expression of the enzyme – it is breaking down HCY to the point that it puts a lot of sulfites out into the urine. So poor man’s way of a tip-off.

Q. So then, in detox protocols, sulfur is pushed heavily… is this a big NO for these people?
A. Let’s use myself as an example…my HCY runs around 5 to 6 and I have a block in that pathway. I used eat a lot of dried fruit because I wanted the fiber, magnesium and potassium but I stopped because of the sulfites. I used to drink red wine but stopped – again because of the sulfites. You can get low-sulfite organic wines…grown specifically not to have the high levels… and some white wines are lower in sulfite than red. These people should be careful of sulfur in the diet …not to consume an overload in one day. Too much at one time can give a toxic load and you’ll feel sick the next day.

By the way. there is a phenomenal amount of work done by Amy Yasko Ph.D., NHD, AMD, HHP, FAAIM on methylation pathways, autism, chronic fatigue and all the related issues. [www.dramyyasko.com]

Just do a Google or start here: [www.ch3nutrigenomics.com]

Also…the doctor who is really on top of this and who wrote the introduction to my book, Metabolic Cardiology, Jim Roberts, Cardiologist, who is way ahead of his time regarding this… his website (heartfixer.com) has an excellent methylation discussion. Dr. Sinatra says, “It’s the best I’ve seen on how to involve these pathways in clinical practice.”

[www.heartfixer.com]# (Methyl Cycle Genomic Analysis and Supplementation)

(End of Sinatra notes on Methylation).

REFERENCES, READING RECOMMENDATIONS

The Biology of Belief (Epigenetics) 2005 Bruce H Lipton, PhD

The Genie in Your Genes: Epigenetic Medicine and the New Biology of Intention 2009, Dawson Church. PhD

Epigenetics. (review) Julie Klotter. Townsend Letter: The Examiner of Alternative Medicine. Feb-March 2007 i283 p28
In 2000, Duke University professor Randy Jirtle and postdoctoral student Robert Waterland put female agouti mice on a methyl-rich diet just before conception. These mice are uniformly fat and yellow. The gene that controls their appearance also increases their susceptibility to cancer and diabetes, shortening their lifespan. Instead of producing uniform replicas of themselves, the mice on the methyl-rich diet produced a majority of slender, brown offspring. These brown mice did not have the tendency for cancer or diabetes and lived to old age. Pharmacologist Moshe Szyf at McGill University (Montreal, Canada) and other researchers have discovered that methylation also affects genes associated with cancer. If genes that promote cancer are undermethylated, tumors can grow. If genes that suppress tumors are overmethylated, metastasis can occur. ) Continue: . [www.goodlifewellnessinc.com]

Professor Randy Jirtle of Duke University explaining the science of epigenetics – [healthandenvironmentonline.com]
Director of the Epigenetics and Imprinting Laboratory, Duke University [randyjirtle.com]
[randyjirtle.com]

Do a Google on Randy Jirtle and the Tale of the Agouti Mice.check the photos. [epigenie.com]

A missense mutation in the Kv1.1 voltage-gated potassium channel–encoding gene KCNA1 is linked to human autosomal dominant hypomagnesemia J. Clin. Invest. 119(4): 936-942 (2009).
Bob Glaudemans1, Jenny van der Wijst1, Rosana H. Scola2, Paulo J. Lorenzoni2, Angelien Heister3, AnneMiete W. van der Kemp1, Nine V. Knoers3, Joost G. Hoenderop1 and René J. Bindels1
Results: A heterozygous KCNA1 A763G mutation is causative for hypomagnesemia

Benjamin Lynch, ND – Interview Methylation Do’s and Don’ts
Websites - [mthfr.net] and [www.seekinghealth.com]

Dr. Lynch’s video presentation is Improving Patient Outcomes- Identifying Common Methylation Polymorphisms His website has a forum and research plus other articles of interest on this topic. Dr. Lynch’s details for detecting and treating methylation defects including the MTHFR gene aberration can be found at [www.seekinghealth.com] . It is a 45 page PowerPoint presentation and there is also a narrated version at the following link if you’d rather listen and follow along with the visual presentation…… [www.youtube.com] The You Tube version has asides and comments that emphasize and help clarify.

Kilmer McCully, MD
Biography Kilmer S. McCully, MD received his A.B. degree magna cum laude (chemistry) from Harvard College in 1955 and his M.D. degree cum laude from Harvard Medical School in 1959.

He was elected to Phi Beta Kappa at Harvard College and Alpha Omega Alpha at Harvard Medical School. During medical school, he studied cholesterol biosynthesis in the laboratory of Konrad Bloch at Harvard University and pregnenolone metabolism in the laboratory of Lewis Engel at Massachusetts General Hospital.

Following his internship in internal medicine at Massachusetts General Hospital, he was appointed Research Associate in Biochemistry at National Institutes of Health in the laboratory of Giulio Cantoni, where he studied tRNA structure.
Continue [www.spacedoc.com]

Kilmer S. McCully, MD – The Father of Homocysteine
Topic: “The Homocysteine Revolution—Medicine for the New Millennium'” Interview

Meet Dr. Kilmer McCully
Dr. Kilmer S McCully is currently Chief of Pathology and Laboratory Medicine Service at the US Department of Veterans Affairs Medical Center, Boston. He is internationally recognized for discovering the connection between homocysteine and heart disease and for developing the homocysteine theory of arteriosclerosis. Dr. McCully has published numerous research articles, reviews, editorials, book chapters, two monographs, and two books, The Homocysteine Revolution, in 1997, and The Heart Revolution, in 1999. His books have received national and international media attention in television, newspaper, and magazine articles. He is the recipient of numerous awards, including The Linus Pauling Award in Functional Medicine in 1998. He holds six US patents for antineoplastic and antiatherogenic homocysteine compounds. Previous positions held are Associate Pathologist, Massachusetts General Hospital, Boston, and Pathologist, Veterans Affairs Medical Center, Providence. He has served on the faculties of University of Connecticut, Brown University, and Harvard University, where he is currently Associate Clinical Professor of Pathology. Dr. McCully holds MD and AB (chemistry) degrees from Harvard.

Interview with Kilmer McCully MD on Homocysteine
Part 1… [www.spacedoc.com]
Part 2. [www.spacedoc.com]

The Resurrection of Kilmer McCully Life Extension Magazine…On the Cover – 1997 by Terri Mitchell [www.lef.org]

An interview with Kilmer S McCully, MD by Richard Passwater, PhD. Homocysteine Revolution [www.drpasswater.com]

Kilmer McCully, M.D., Connects Homocysteine and Heart Disease - The July 1999 Issue of Nutrition Science News by Gloria Bucco [www.chiro.org]

The Homocysteine Revolution © 1997 Kilmer McCully, MD Keats Publishing

The Heart Revolution© 1999 Kilmer McCully, MD Harper Collins

Methyl Magic © 199 Craig Cooney, PhD, Andrews McMeel Publishing

Homocysteine and folate as risk factors for dementia and Alzheimer disease © 2005 American Society for Clinical Nutrition [ajcn.nutrition.org]

Homocysteine explanation slide show [www.slideshare.net]

Is Homocysteine Making You Sick? - Life Extension August 2009 [eu.lef.org]

A Review of Folates in Nutrition and Human Health by Jose A. Llobrera, Ph.D
30 page white paper Good overview for research. I have the pdf. Send me a PM with your email and I’ll send.

Methylation: Vital to Cardiovascular Health, Nervous System Function, Immune Strength and More - a monograph published by ProThera on, Winter 2011. If you would like a copy, send me a PM with your email.

James C Roberts, Integrative Cardiologist - Methylation Flow Chart and text explanations of effects of Methylation Defects. [www.heartfixer.com]#

Amy Yasko,Ph.D., NHD, AMD, HHP, FAAIM, is a recognized expert in molecular biology in the field of DNA/RNA based diagnostics and therapeutics and has significant information at her website the methylation cycle.: [www.dramyyasko.com] [www.dramyyasko.com]

Roots of Health and Longevity… Nice explanation of methylation (Root #1) importance and defects and is not overly technical… [www.sentinelsource.com]

Immortality Edge © 2011 – Michael Fossel, MD, PhD, Greta Blackburn, Dave Woynarowski, MD. Wiley Publishing
23andMe genotyping [www.23andme.com]

Health Diagnostics Laboratory Inc -1-877-443-5227

Folic Acid Controversy – December 2007
Summary
There is no question that low folate status is associated with neural tube defects, decreased cognitive function, elevated plasma homocysteine, risk factor for CVD and stroke, dementia and Alzheimer’s disease, cancer risks and depression. However, there is growing evidence of the potential health risks associated with unmetabolized folic acid in the blood circulatory system. Therefore, dietary supplementation of folic acid in addition to consumption of folic acid fortified foods should be carefully evaluated among potential risk groups. The controversy now emerging around folic acid is more applicable to mass food fortification efforts, which do not discriminate between the general population and at risk populations (i.e., cancer patients, elderly, etc.). Folic acid supplementation, including the levels in commercial multivitamins, for non-risk populations appears to be generally beneficial.

Send me a PM with your email if you would like a pdf copy of this report.

Jackie, thanks. I haven't studied this topic much (yet) and so it was a very helpful post for me. If we each have about a 50/50 chance of having a gene mutation affecting methylation dysfunction, I certainly want to know more about epigenetics. And, although just one part of the picture, I'm now curious what my homocysteine level is, among other things.

Many thanks for all the hard work Jackie,

We should make this an AFIB Resources link as well so people can have easy reference and access to it. Methylation dysfunction either from genetic reasons or acquired is a significant issue for many people around the world and its great to have so many good resource links and explanations in one spot!!

I very much appreciate the major effort and amount of work you put into this timely and interesting topic on our behalf Jackie!

Cheers
Shannon

Jackie,

Once again, your research is wonderful, and I certainly appreciate all your time and effort in presenting this important topic to us.

The problem is that so few doctors know how to treat methylation problems, or even want to learn about it. My nutritionist is in the learning process, but he is learning from the best. He uses Dr. Yasko's book as a treatment guideline, and has read much of Dr. Lynch. In fact, he will be taking an online class from Dr. Lynch in March. The problem is that using "formula" treatment plans just don't work. Because my nutritionist uses ART (autonomic response testing), a form of advanced muscle testing, he knew not to give me some of the supplements that Dr. Yasko considers standard for her patients, as I would have had a bad reaction. Even so, we've made some mistakes along the way. For example, we found that I do better with hydroxol B12 than with methyl B12.

I was fortunate that I got my 23andme report last November. The fee for the saliva test and report was only $99! But now the FDA is trying to shut them down. There are other genetic testing companies, but they are pricey. The heartfixer website is a great source of information and very readable for the average lay person.

Nancy M

Randy - Thank you.

And thank you, too...Shannon and Nancy - these were only part of the notes from the extensive interview - much was discussing dosage and other precautions that weren't appropriate to post here, but the the major point Dr. Lynch made is that it's harmful to patients when they are treated to the "flare" level and practitioners should proceed with caution so they don't make their patients even more ill than they already are.

One of the major points was that patients absolutely must have proper liver function and good detoxification function before embarking on the methylation improvement protocols. It's imperative to normalize that first. Otherwise, patients become even more ill and often, severely ill and have to go to the ER.

My initial NutrEval results indicated an abnormality in the methylation pathway, but before addressing that, I first had to go through several months of detox protocols;then retest before we started on correcting methylation. It took some time but eventually normalized. My problem was initiated by the multiple chemical exposures and resultant sensitizing so liver clearance was impaired but once that normalized, I felt better. This was long before afib entered the scene which we now think was caused by the Lyme exposure that happened over ten years prior to that. It's been a long journey.

Jackie

If you Google "Methylation Dysfunction", there are a bunch of references on this very interesting topic. Most of the links are not related to heart issues; however, there are quite a few links related to its connection with bipolar disorder, depression, and schizophrenia.

Tom P



Edited 1 time(s). Last edit at 02/12/2014 11:04AM by Tom_P.