This is a follow-on writing treatment of methylation chemistry, as was introduced in the last Journal editorial about the problems I perceived in the June, 2014 edition of Southern Living…a magazine of sorts, and also a kind of lifestyle of sorts; both the magazine and the lifestyle having their attendant concerns. You can review the prior Journal for my unabashed assessment of that edition.
One of the most important biochemical additives for a smooth ride in life is the mitochondrial concoction covered in the previous “Minding your Mitochondria” entry which dealt with the biscuit poisoning problem as was espoused in the May edition of Southern Living.
Another outstanding health additive and overall vehicular lubricant catalyst is the addition of what we will now focus on…some tuned up methylation chemistry.
This important biochemistry is an intricate set of jeweled gears and spindles…let’s have a look…
Methylation encompasses a host of major biochemical processes of overarching significance. The processes of methylation involve putting a methyl group onto a chemical in the body to change its structure and its function, and thus make it amenable for its next necessary step in the geared wheels of life.
A methyl group is a carbon with 3 attached hydrogen atoms. Since carbon binds at 4 different points, the methyl group has one binding point unsatisfied. It has to find something to attach to, and there happen to be a plenitude of things that want to attach to it. Methylation biochemistry is often referred to as Folate One-Carbon Metabolism (FOCM). There are a number of important methylation enzymes playing key functional biochemical roles in our lives. This Journal will consider 2 very important ones, and will reference and link to some other important ones.
Methyl groups are used all over our innumerable biochemical pathways by attaching to certain chemicals to alter them for further metabolic pathways of utilization or detoxification, or by catalyzing key enzyme pathways of health. These methylation reactions occur at the multi-nano level of times per second all over our biochemistry.
A few key methylation biochemical conversion activities include:
- Cellular repair by synthesis of nucleic acids, production of, and repair of DNA and transfer/messenger RNA
- Regulates DNA expression
- Detoxification via direct chemical alteration and elimination via Phase II liver enzyme methylation pathways
- Immune system support
- Neurotransmitter production by inter-conversion of amino acids
- Blood cell formation of red cells, white cells, and platelets
- Folate one carbon metabolism (FOCM) of other sorts all throughout the biochemistry, to make things like carnitine, creatine, nitrous oxide, phosphatidylcholine, CoQ10, melatonin, and glutathione (GSH)
- Contributes to the production of ATP in the mitochondria
- Participates in cholesterol chemistry
All methylation chemistry is initiated by the rate controlling (rate limiting) activity of a key enzyme in our bodies conveniently fully hyphenated for this writing as methylene-tetra-hydro-folate-reductase, or, MTHFR.
MTHFR is an enzyme which is responsible for converting 5, 10 methylenetetrahydrofolate to 5, methyltetrahydrofolate (5-MTHF), which is folate, or, vitamin B9. 5-MTHF is involved in many important methylation processes, such as the metabolism of homocysteine (a potentially toxic amino acid) into methionine (a useful and necessary amino acid).
Single Nucleotide Polymorphisms…and MTHFR
An entire set of 23 human chromosomes is called a genome. The human genome is composed of 3 billion base pair sequences of the nucleotides adenine, guanine, cytosine, and thymine. A variation from normal at a single base pair site is a mutation, as compared to other members of the same species. If this mutation is present in more than 1% of the population it is called a single nucleotide polymorphism, or, a SNP. The term “polymorphism” just means “many forms,” and relates to the fact that a single gene encoding for an enzyme may have different forms active at once. For instance, as we shall see below, there are 2 important polymorphisms of the MTHFR enzyme family.
Since the human genome project was initiated in 2003, over 10 million SNPs have been identified in the human genome. SNPs account for our differences, how we develop diseases, and how we deal with pharmaceutical drugs.
SNPs have evolved over thousands of years, and at this point in our learning curve, it is estimated that we all have about 1000 important SNPs in our genetic coding for the enzymes which control vital chemical processes. Thus, we are all mutants from the normal wild type somewhere in our chromosomal make-up.
However, most SNPs have little or no negative effects in our lives. SNP’s are more likely to occur in larger enzymes, such as MTHFR which has a make-up of some 500 amino acids and has a molecular weight of 77,000 (77 Daltons). In this enzyme a SNP in the genes which code for its function will alter just one amino acid in the enzyme’s structure, and that is enough to reduce its functionality.
And so, MTHFR is produced in our body from our own particular genetic coding for such. There are common genetic variants of this enzyme production which are caused by particular SNPs. The enzyme then functions at a lower than normal rate. This can lead to a variety of important health problems. Although there are over fifty known MTHFR mutation variants, the two primary common ones are called C677T and A1298C.
For the C677T variant there is a mutation from the DNA nucleotide cytosine to the nucleotide thymine at position 677 within the gene. For the A1298C variant there is a mutation from adenine to cytosine at position 1298 within the gene. These coding variants lead to amino acid differences in the MTHFR protein that reduces its ability to function optimally. This lower function can result in problems such as is noted in the list above, and in the disease list below.
The C677T variant is commonly associated with early heart disease and stroke and the A1298C variant with a variety of other chronic illnesses and neurological disorders. Laboratories can check for MTHFR SNPs and will report results as heterozygous or homozygous.
Other Methylation Enzymes are Important
In addition to the A1298C and C677T MTHFR enzymes there are other very important methylation enzyme alleles which are common SNPs. These SNPs will usually show up on expanded gene carrier status reports such as the one offered at www.23andMe.com (to be covered below).
What are the possible genotypes which a lab will report?
The 677 site can be reported out as CC (normal homozygous), CT (a heterozygous variant which affects about 25% of the population with some reduced MTHFR activity) or as TT (a homozygous variant with 2 altered copies affecting about 10% of the population and is at increased risk for cardiovascular problems).
The 1298 site can be reported out as AA (normal homozygous), as AC (heterozygous for 1 variant) or CC (homozygous for 2 variant copies affecting about 30% of the population, with reduced MTHFR activity of up to 60%, and is associated with increased significant disease risk if found together with a 677 variant).
A simple and very incomplete listing of some diseases associated with MTHFR mutations follows. A complete list grows longer and longer as the importance of this issue becomes more apparent and mainstream.
Physicians should now be routinely screening for MTHFR SNPs, and other types of SNPs as well.
Notice that IBS, depression, and diabetes, which were showcased in the aforementioned Southern Living pharamceutical ads, made this list (see the last Journal treatment of these 3 disorders), but don’t expect Southern Living to run a damage-control special on this concern.
- Addictions: smoking, pharmaceutical and recreational drugs, and alcohol
- Allergic reactions
- Alzheimer’s disease
- Anger compulsion
- Atherosclerosis of coronary and peripheral vessels
- Autoimmune disorders such as MS, lupus, rheumatoid arthritis
- Bipolar disorder
- Blood cell production by bone marrow
- Bowel dysfuction
- Breast cancer
- Cancer, many, if not most types
- Chemical sensitivity
- Chronic bacterial infections
- Chronic fatigue syndrome
- Chronic viral infections
- Chronic pain
- Cleft palate
- Congenital heart defects
- Cytoskeletal breakdown
- Down’s syndrome
- Erectile dysfunction
- Frequent blood clots
- Frequent miscarriages
- Heart disease
- Heavy metal toxicities
- Homocysteine elevation
- Huntington’s disease
- Immune system dysfunction
- Increased sensitivity to chemicals, pharmaceuticals, supplements
- Infertility, male and female
- Irritable bowel syndrome
- Language and cognition impairment
- Leaky gut
- Migraine headache
- Mitochondrial disease
- Multiple chemical sensitivity syndrome
- Multiple sclerosis
- Neural tube defects
- Parkinson’s disease
- Pulmonary embolism
- Renal failure
- Rett’s syndrome
- Rheumatoid arthritis
- Skin disorders, all types
- Sleep disorders
- Spina bifida
- Systemic lupus erythymatosis (SLE)
- Thyroid dysfunction
…and there is more to add to this list.
I now believe that almost everyone who has been a patient of mine may have been a patient because of MTHFR mutation issues, as well as other types of SNPs which govern associated biochemical pathways.
Lab Testing for MTHFR Mutations
You can order your own test kit for $199 from 23andMe (www.23andme.com). If you use this lab test, 195 gene sites will be analyzed for mutation variants. Categories studied include abnormalities in enzyme activity responsible for detoxification, methylation, neurotransmitters, cardiovascular chemistry, digestive chemistry, vitamin receptor activity and chemistry, and mitochondrial antioxidant chemistry.
You will get back data results only for the variant alleles. An allele is a gene base pair site on the chromosome. You may have several dozen SNPs; the usual number in my experience is 50-70 different allele mutations on a 23andMe testing. This information is incredibly important to know about.
The information of your gene carrier status from 23andMe will be indecipherable as practical information until you run this information through other useful interpretive app sites.
Many of your individual mutations may not be overly important, but a negative synergy of them can become important.
Don’t be overly alarmed, but do be proactively engaged with this kind of vital information. It will only help save you from the typical diseases in our society, and attendant visits to the medical industry.
A most useful interpretive site for 23andMe users is NutraHacker. This site app will charge you $23 to give a nutrigenomic interpretation of your gene carrier status. Here you can learn what supplements you need to take, and which ones you may need to avoid, due to your mutations.
So, you get information to help you streamline your nutritional and lifestyle epigenetic practices. You can mitigate any negative effect which the SNP may cause by such a proactive approach. You also get pharmacogenomic information about what pharmaceuticals you should be wary of due to drug metabolism and detoxification mutations.
Another site which will offer interpretation of 23andMe data is www.geneticgenie.org. The information is limited at present to only methylation and detoxification pathways. This service is free, but a small $5 to $10 donation is requested for report generation.
Another service to help you interpret this data is Sterling Hill’s application at www.mthfrsupport.com.
More bits of information may be found at www.snpedia.com.
Other labs which can supply you with testing for MTHFR mutations are LabCorp, Quest, and SpectraCell Labs. Your doctor will have to order the test kit from SpectraCell. These tests will just be for the A1298C and the C677T sites.
Testing for MTHFR and other types of SNPs is now a mainstream going concern, and should be regarded seriously by everyone.
Except for folic acid, all of the nutrients mentioned below are known methylators, and as such they assist in boosting down regulated or discombobulated methylation pathways. There is also the issue of overmethylation. And so, one can be either undermethylated or overmethylated. You should consult with a knowledgeable and experienced health practitioner about your exact methylation needs before you jump into using these products. Your exact methylation needs are determined by your MTHFR genomic status, your various epigenetic lifestyle practices, your behavioral presentation, and your other types of SNPs.
One of the healthy and essential end products of MTHFR activity is the production in the body of its principle antioxidant and detoxifier known as glutathione, sometimes abbreviated as GSH. One of the ways that MTHFR mutations can make you susceptible to illness is by lowering your ability to make glutathione. People with MTHFR anomalies usually have low glutathione, and this makes them more susceptible to stress, neurotransmitter imbalances, thyroid imbalances, and they are less tolerant to any types of toxic exposures.
Another very important treatment which must be incorporated is the use of vitamin B9, or, folate. Folate is the naturally occurring form of the water-soluble vitamin B9. It is found in foods such as black-eyed peas, chickpeas and other beans, lentils, spinach, turnip greens, asparagus, avocado, and broccoli, but is also available as a supplement.
The human body needs folate to synthesize and repair its DNA. It’s especially important during the kind of rapid cell division and growth seen in infancy and pregnancy. Young children of all ages are in a rapid growth phase, and so folate is essential for infants, toddlers, juveniles, and adolescents. Correct methylation in these ages is so very important not only for healthy DNA and correct physical growth, but also for correct central nervous system growth.
Children and adults both require folate to produce healthy red blood cells and prevent anemia, as well as enhancing many other vital functions; especially the normal growth of their rapidly dividing cells.
Use Natural Folate…Do not use Folic Acid…Know the Difference Between the Two
Folic acid, on the other hand, is synthetically and cheaply produced, and refers to just one member of the folate group: pteroylmonoglutamic acid. While folic acid occurs only rarely in whole foods, it is extremely stable and cheap, which is why it is synthesized and widely used in dietary supplements and to “fortify” processed foods. To say that such “fortified foods” are healthy is just a mild form of madness.
Crestone and Beyond recommends that you eliminate any of your vitamin supplements which use folic acid and work through a supplement line, such as Designs for Health, and a few others, which only use real folate. This company’s entire product line can be accessed through this website store. A significant number of their products are oriented to assist methylation pathways.
For instance, Designs for Health has a variety of supplements which contain natural folate. This correct form of vitamin B9 is contained in all of the company’s multivitamin supplements. It is also in specialty items: the Ultra B12-Folate blend, and also in the Homocysteine Supreme. The latter product is effective in treating those with homocysteine elevations, which carry attendant cardiovascular risk. In addition, the vitamin B9 folate is offered as a stand alone product for use by those with more significant MTHFR mutations, such as L-5-MTHF, which comes in 2 strengths.
The important thing to remember is that folic acid is not biologically active, although for most people the liver can convert it to the folate we need. Most, however, does not mean all. It’s estimated that 30% to 40% of the population can’t efficiently convert synthetic folic acid into folate because of MTHFR mutations. I am beginning to wonder if this number is actually higher. The penetration of MTHFR mutations in our general population may well be 1 out of 2 people.
According to the fact that 30 to 40% of people cannot efficiently convert folic acid to folate, about a third of our population has two potential problems: a deficiency in folate (because it is hard to get enough from a diet full of processed, but “fortified” foods), and possibly even an excess of folic acid (because their body can’t metabolize what could become an overabundance of folic acid present in “fortified” foods).
It is important to know the difference between folic acid and folate as is further elucidated in this article.
Folate deficiency is a very serious medical condition, leading to Alzheimer’s and other brain diseases. If pregnant women are deficient in it, it can also lead to spina bifida and other neural tube and midline birth defects in their children. You will notice some of these types of congenital defects in the list above.
For women who are pregnant, I recommend Designs for Health’s Prenatal Pro Essential Packets. This product has correctly formulated multivitamins, omega fats, bone minerals, and nice arrangements of vitamins D, K1 and K2. There is no folic acid, but there is good amounts of folate.
All who contemplate pregnancy, or are pregnant, should be tested for methylation SNPs. This is just imperative so that the unborn child can be given the best biochemistry in utero.
Compared to other expensive and exotic lab tests, testing for MTHFR mutations is highly cost effective and of great value. Commonly this test costs $100 to $150. The information gained is important, and is easy to address by lifestyle and epigenetic modification. And yes, your insurance usually covers the testing. After all, the medical insurance companies know that it would serve their future bottom line to cover such testing. The medical insurance companies are actually ahead of the medical people in this learning curve.
Regarding the folic acid to folate conversion deficiency problem, too much unmetabolized folic acid can build up in the blood, which could lead to an increased risk for prostate, lung, and colon cancer, or worsen already present cancerous lesions.
Other therapeutic considerations to be used in MTHFR mutation conditions may include the use of:
- methyl-B12 in oral form (can also be administered in sublingual, intranasal or intramuscular forms)
- other B vitamins as determined more accurately by intracellular nutrient profiles (see www.SpectraCell.com) vs. routine blood studies
- S-adenosyl methionine, or, SAMe, an excellent methyl donor, and is considered to be the universal methyl donor
An Important Therapeutic Caveat
If one has a double homozygous mutation then they may be unusually sensitive to any of the various supplements mentioned above. In these cases the supplements must be added slowly, one at a time, and changes observed before adding in another supplement. Those with a double homozygous mutation are probably already under some health professional’s care for a variety of our society’s complicated disorders, or combinations of disorders. Unfortunately for these millions of patients, the underlying and foundational chemistry is most likely going unrecognized.
Unless such patients with significant methylation SNPs get correct methylation assistance, their lives will never be normal. It is possible to register this same line of opinion for all of the types of other genomic SNPs.
Unfortunately, the average conventional medical practitioner is relatively clueless and unknowing about methylation chemistry and MTHFR mutation conditions. You may have to educate your own physician. Some of them actually do listen to their patients.
Last but not Least
Crestone and Beyond cannot apologize for the complexities of methylation chemistry, and offers a further Disclaimer to the reader that the above explanations are somewhat simplified, but do present some of the basic information, nonetheless.
Crestone and Beyond also cannot apologize to the reader for the problems being created for our health by 1) pervasive purposeful misinformation campaigns, 2) abundant unknowing misinformation sources, 3) food industry and supplement companies’ use of folic acid, and 4) addictive consumerist trends, capitalistic greed, and all of the power struggles resulting from these pervasive social addictions.
Therefore, Crestone and Beyond cannot apologize for the excellent length of this minor thesis, as presented in Parts I and II. The Part I preamble was necessary just to paint a picture of our commonly moving sideways social ignorance and how it is underscored and enabled by bad print and other forms and sources of misinformation.
Crestone and Beyond does recommend some further reading on the methylation subject for the curious and motivated student.
A useful website for practical information is the methylation dedicated website of Dr. Benjamin Lynch at www.mthfr.net.
Imagine looking through the glass backing on a finely jeweled watch. You can see all of the superficial gears moving in their synchrony. What you can’t see are all of the other gears beneath this superficial layer of turning jeweled gears. There are experts who understand all of the deeper layers of the turning biochemical wheels of life.
Dr. Walsh has the longest career of research in this field (some 35 years) and his contributions have come in the arenas of brain chemistry, neurological, and mental disorders. Currently, Dr. Walsh is busy teaching physicians about methylation chemistry. Dr. Yasko has a rich research and clinical experience, and her evolved expertise is in the treatment of autism. Both of these individuals have written very important books in this field of health.
Dr. Walsh’s book is entitled Nutrient Power, Heal your Biochemistry and Heal Your Brain, published in 2012.
Dr. Yasko has published 4 books. Her first book is regarded as a seminal text and was published in 2005…Genetic Bypass: Using Nutrition to Bypass Genetic Mutations. This book is its own university.
For the beginner who seeks practical assistance I recommend her 2014 publication…Feel Good Nutrigenomics. In this book she uses an analogy which I like to use…she alludes to the body as being like your automotive vehicle.
Drive a Well Tuned Four-on-the-Floor Model
Crestone and Beyond recommends a well tuned four-on-the-floor (body-mind-emotion-spirit) standard shift for your driving delight. The chassis, engine, controls, drive train, and suspension do not need to be overly souped up in any special manner, but should be well engineered, well maintained, and stream-lined to handle any road condition with ease. These integrated vehicles are a delight to drive and even have their own built-in vehicular repair mechanism. You may not ever even need a mechanic to service your vehicle except for the most minor considerations in the event you should manage to sabotage your built-in vehicular repair mechanism.
May you enjoy your ride in your vehicular ego container in this spin through life. Please remember that you will need a well managed and healthy ego to heal with. You may need this intact ego to tell your doctor that you want MTHFR genetic testing!
You may also require such a healthy ego to help your doctor’s understanding of this vital health information…or…at the very least, you may need to override your doctor’s anchoring bias problem against “unnecessary lab tests.” In my long experience in the medical industry, physicians are usually down on what they are not up on.
Patients are usually the best educators of doctors, even though the word “doctor” is from the Latin word “docere” which means “teacher.”
You will also need this healthy ego so that you can keep that four-on-the-floor drive as pleasant and as steady and as fun and as rewarding as possible. If you hit a serious bump in the road, make sure you call the right kind of mechanic.
And finally…just one more slight against the magazine publication which has prompted the writings on mitochondria and methylation and all of the hoopla of attendant editorial. The July edition of Southern Living has just arrived smelling like it has been doused in a spray of some bad toxic perfume. I am sure that whatever the printers of the magazine sprayed on would not pass muster with the Environmental Working Group. The VOC level from this edition is high enough to require a HEPA filter face mask type of encumbrance on one’s face just to turn the pages of the thing. I swear…
It literally reeks…no…it stinks to high heaven, as we say down South.
I’m sure that they over-treated the magazine since most of this print is headed to the South land where the humidity is high and the atmosphere is dense. Out here where I live down at the end of this county road at 8000 feet the humidity is low and the air is considerably thinner. Perhaps that is why this magazine has such an enhanced olfactory effect…there is not as much atmospheric density to compete with and impede the off gassing of whatever the good folks over at Southern Living treated that paper with.
A summertime image of Jennifer Aniston is on the back cover sporting a smile, a bikini look, and some Aveeno sunscreens which do not receive very good ratings from the Environmental Working Group’s personal products’ toxic chemical ratings. I looked them up at the EWG website. They are just one more toxic slather for your skin and internal methylation pathways to deal with.
This issue of Southern Living deservedly rests in my recycling bin where it was unceremoniously tossed. Maybe it can at least assist in saving another tree.
The next Journal introduces the one addiction that we all have…our addiction to thinking.
Thank you for reading.
Signing off from Crestone…and Beyond
- Enigmatic chemical tag is altered in autism brains
- Dispelling a Methylation Myth…nutritionist Christiana Paul and naturopath David Brady cover the different forms of vitamin B12 and their biochemical relationship and functions.