This is a collection of some articles about the MTHFR gene mutation. (Full Text, followed by the link to the source.) Some are personal stories, written by people who have spent a lot of time figuring out their health issues, and others are of a more scientific tone. Bottom line is: this is a significant medical concept which accounts for much of the chronic disease seen in today's population in the western world, particularly in the United States.
JJR
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MTHFR
The doctors at Functional Endocrinology of Ohio continue to be on the cutting edge of health care. We check for the MTHFR genetic mutation when the case history warrants. Dr. Ungar is certified in methylation and clinical neutrogenomics by the Seeking Health Educational Institute.
You may have seen a little bit about MTHFR in health-related news. So, what exactly is it?
The MTHFR genetic mutation, or polymorphism was first discovered as a result of the human genome project (C677T in 1995 and A1298C in 2001). The gene produces the MTHFR enzyme, and people who have this mutation have a reduced ability to process folic acid/folate into something their body can use.
MTHFR (Methylenetetrahydrofolate Reductase) is the name of the gene and the enzyme that plays an essential role in processing the folate we eat into a nutrient our bodies can utilize.
People who have MTHFR mutations have an interruption in the “Methylation Pathway." Methylation affects more than 20 different processes in our bodies and when methylation is interrupted, many many essential body functions are disrupted. This can be worked around by taking the nutrient as supplements that cannot be made because of the missing enzyme. In the case of the A1298C mutation, where there should be an Adenine it is switched to Cytosine.
The functions of methylation include:
Turn on and off genes (gene regulation)
Process chemical and toxins (biotransformation)
Build neurotransmitters (dopamine, serotonin, epinephrine)
Process hormones (estrogen)
Build immune cells (T cells, NK cells)
DNA and RNA synthese (Thymine aka 5-methyluracil)
Produce energy (CoQ10, carnitine, ATP)
Produce protective coating on nerves (myelination)
Prevalence - MTHFR mutations are very common. 20-40% of caucasions have one copy of the mutation. 4-14% have two copies. Somes statistics I have seen says 40% of people have one copy, and 30% have two copies. Just because you have the mutation does not mean you will show symptoms or develop conditions associated with MTHFR. Why? Because there are other mutations that could factor into things, and also environmental factors. This is big. People with MTHFR have a reduced ability to eliminate toxins and heavy metals, so the cleaner their environment, the better. This also explains why two people can have the same mutation and not be affected equally.
Folate is essential for cell growth and reproduction, the breakdown and utilization of proteins, the formation of nucleic acids, red blood cell maturation, and a variety of CNS reactions. Both folic acid and dihydrofolate are not biologically active forms of folate, but are essentially pro-drugs, and must undergo enzymatic transformation to L-methylfolate in order to be used by cells, and unlike other forms of folate, L-methylfolate readily crosses the blood-brain barrier for use in the CNS. It is impossible to get L-methylfolate from food. One has to get L-methylfolate through supplementation.
According to Dr. Ben Lynch:
Possible symptoms associated with A1298C MTHFR mutations
- hypertension
- delayed speech
- muscle pain
- insomnia
- irritable bowel syndrome
- fibromyalgia
- chronic fatigue syndrome
- hand tremor
- memory loss
- headaches
- brain fog
Possible signs associated with A1298C MTHFR Mutations
- elevated ammonia levels
- decreased dopamine
- decrease serotonin
- decreased epinephrine and norepinephrine
- decreased nitric oxide
- elevated blood pressure
- muscle tenderness
- ulcers
- pre-eclampsia
Possible conditions associated with A1298C MTHFR mutations
- fibromyalgia
- chronic fatigue syndrome
- autism
- depression
- insomnia
- ADD/ADHD
- irritable bowel syndrome
- inflammatory bowel syndrome
- erectile dysfunction
- migraine
- Raynaud’s
- cancer
- Alzheimer’s
- Parkinson’s
- recurrent miscarriages
This list of signs, symptoms and conditions continually changes based on research!
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Rather than enjoying the youth and virility of my twenties, some of the “best years of my life,” I suffered from a decade of chronic illness. It started with severe leg swelling and chronic pain on a daily basis. By mid afternoon,
I carried what felt like bricks of water in my legs. On top of that, I was plagued by chronic digestive issues that left me feeling sick, lethargic and just plain gross. This was what I suffered from before I started my journey of detox, which led me to feeling alive, healthier and more energetic than I had felt in over a decade.
One of the crucial things I learned on my healing journey is that because we are all encoded with a unique DNA, each of us has a unique response to chemical toxins and how well we methylate. Some of us can detox and process these toxins, while some of us cannot. I, for example, was born without the enzyme MTHFR, an enzyme that doesn’t allow me to detox properly. This is why some people feel sick when they walk into a store with perfume and others don’t have any trouble and why some people get sick from mold exposure while others don’t show any symptoms. And also, why some of us have a hangover after drinking, while others are fine the next day! Some people cannot detox these toxic substances from their bodies, and in turn, they need a little extra support. Many other people like me, who have this MTHFR missing enzyme, can work with their Integrative Medicine M.D.’s to help their bodies remove toxins.
Methylenetetrahydrofolate reductase (MTHFR) is both an enzyme and a gene; it is crucial to the body because it processes folate (folic acid) for our bodies to utilize it. Mutations in this gene result in decreased activity of the enzyme, which causes issues with the methylation in our body, leading to important body functions to become disrupted – which include the ability to eliminate toxins properly. Methylation is an important biochemical process that is essential for the proper function of nearly all of your body’s systems; it occurs billions of times each second and helps repair your DNA, controls homocysteine, recycles molecules your body needs for detoxification, helps keep inflammation in check and maintains your mood. To avoid serious conditions that are caused by the breakdown in methylation, the key is to maximize methylation (protect your methylation) by understanding what affects your methylation process such as toxic exposure, smoking, medications, poor diet, malabsorption and decreased stomach acid.
The main goal to help my missing MTHFR enzyme as I mentioned above is to optimize methylation, which refers to a series of approximately 100 reactions that are responsible for the production of T-cells (immune cells), glutathione (vital for immune function), energy production and for creating dopamine and serotonin. Anyone with 1 or 2 copies of MTHFR, the enzyme that converts folic acid into methylfolate, like myself, tend to have lower immune function. Myself and anyone lacking the MTHFR enzyme can benefit from taking B12 and methyl folate; they work together and are prime components for methylation reactions.
My lack of MTHFR has forced me to take precautions, while other people can detox easily and remove toxins, I cannot. A good place to start cleaning up your lifestyle is with your food. Eating more dark, leafy greens such as dandelion, mustard, collard, beet greens, spinach, kale, watercress, bok choy, escarole and Swiss chard, which are the most abundant sources of the nutrients our bodies need for optimal methylation. Also, looking for good sources of B vitamins from your food such as sunflower seeds, eggs, walnuts, almonds, whole grains and asparagus. Probiotic-rich foods are also a plus because they keep your gut healthy so you can properly absorb the vitamins you get. I use organic sauerkraut, chickpea miso and kimchi. Start by reading labels and eating organic fruits and vegetables from the
Dirty Dozenwithout pesticides, herbicides and other chemicals. You can also eat organic meats, poultry and eggs so that you are not ingesting growth hormones or antibiotics from the animals. I am a dedicated organic consumer – but I wasn’t always. It wasn’t until I learned what those pesticides, antibiotics and growth hormones were doing to my body. Now, I eat a 100%
organic whole food diet filled with lean proteins, healthy fats and a wide variety of fresh veggies. I avoid seafood that is high in heavy metals such as tuna and swordfish, I cannot eat anything out of a can or box because my body reacts to them – so I eat pure, clean, whole foods. Healthy fats such as nuts, seeds and avocados as well as veggies such as spinach, bok choy, Swiss chard, collard greens, sweet potatoes and kale and protein such as chia seeds, ground flax seeds, and organic poultry are a part of my daily eats. It’s tough, but it’s doable and let me tell you – I feel 100% better after removing the toxic junk that was in my life.
Detoxing and methylation are the links to better health that I believe is missing in Western medicine. Trust me; there is hope. There is an answer. Breathe, meditate and focus on the present. Take everything one day at a time; you will get there. You will heal. Your answer IS out there.
http://www.drfranklipman.com/a-story-of-healing-detoxification-and-mthfr/
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What a healthy MTHFR gene does for you
In 2003, a genetic study called the Human Genome Project was completed. And via that study, they discovered that an important gene towards your health and well-being, called the methylenetetrahydrofolate reductase (MTHFR), was defective in a lot of folks!
When it’s all working right, the MTHFR gene begins a multi-step chemical breakdown process, aka methylation, which in simplified terms, is like this:
- The MTHFR gene produces the MTHFR enzyme.
- The MTHFR enzyme works with the folate vitamins (B9, folic acid), breaking it down from 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate
- 5-methyltetrahydrofolate helps convert the amino acid homocysteine down to another essential amino acid, methionine, which is used by your body to make proteins, utilize antioxidants, and to assist your liver to process fats. Methionine helps with depression and even inflammation. It also helps convert estradiol (E2) into estriol (E3)!
- Methionine is converted in your liver into SAM-e (s-adenosylmethionine), which is anti-inflammatory, supports your immune system, helps produce then breakdown of your brain chemicals serotonin, dopamine and melatonin, and is involved in the growth, repair and maintenance of your cells.
- i.e. a proper methylation pathway like the above is going to mean you will have a better chance in eliminating toxins and heavy metals, which can reduce your risk for cancer and other health issues, and put less stress on your adrenals.
What a defective (mutated) MTHFR gene does to you
- It produces a defective MTHFR enzyme of different varieties i.e. it functions less than optimally, such as performing at only 40% of its capacity, or 70% of its capacity. It can mean you won’t break down toxins or heavy metals well i.e. you could find yourself with high iron, or high copper, or high lead, or high mercury….etc. High copper can also cause low ferritin, even though your iron levels look great!
- The defective enzyme doesn’t break down folate vitamins properly (of which folic acid is the precursor to), which can cause high homocysteine, which can increase your risk of coronary heart disease (arteriosclerotic vascular disease or venous thrombosis), and related heart and BP conditions, as well as increasing your risk for dementia.
- Homocysteine is poorly converted to glutathione, which is your body’s chief antioxidant and detoxifier. You are then more susceptible to stress and toxin buildup.
- Homocysteine is poorly converted to methionine, and less methionine can raise your risk of arteriosclerosis, fatty liver degenerative disease, anemia (see Wiki), increased inflammation, increased free radical damage… and produce less SAM-e
- Less SAM-e can increase depression
- And more broadly, an MTHFR defect can increase your risk of a variety of cancers (including breast and prostate cancer), stroke, heart problems, congenital defects, depression, IBS (irritable bowel syndrome), miscarriages, migraines, chemical sensitivities and many conditions.
- You can find yourself with high folate or high B12 i.e. your body will have problems converting inactive forms of folate and B12 to the active forms. So the inactive folate or B12 will simply build up in your serum, also inhibiting the active forms. Most serum folate tests are actually measuring folic acid, which needed to be converted to methylfolate to be used metabolically.
- The Journal Molecular Psychiatry states that “Schizophrenia-like syndromes, bipolar disorder, Parkinson’s disease, Alzheimer’s disease and vascular dementia have all been associated with one or more mutations of the MTHFR gene”. (2006;11, 352–360)
More than one mutation of the MTHFR gene
Genes are passed down by your mother and your father. Most literature states there are a good 40-50 different mutations of this important gene which could be passed down by one, or both or your parents. But only two are particularly problematic: mutations on the points at C677T and A1298C. The numbers refer to their location on the MTHFR gene. You will also sometimes just see them written as just 677 and 1298.
There are many combinations of MTHFR:
- Homozygous: means you have both copies of either the 677 mutation, or the 1298 mutation, one from from each parent.
- Heterozygous: means you have one copy of either the 677 mutation, or the 1298 mutation, plus a normal one from the other parent.
- Compound Heterozygous: means you have one copy of the 677 mutation from one parent and one copy of the 1298 mutation from the other parent.
- Triple homozygous mutations (more rare): an example would be one C677T, one A1298C, and a P39P or R594Q, for example.
Here are possible combinations:
- Normal/Normal for both 677 and 1298
- Heterozygous 1298 / Normal 677 (i.e. one parent passed down a single 1298 mutation)
- Homozygous 1298 / Normal 677 (i.e. both parents passed down the 1298 mutation)
- Heterozygous 677 / Normal 1298 (i.e. one parent passed down a single 677 mutation)
- Homozygous 677 / Normal 1298 (i.e. both parents passed down the 677 mutation)
- Heterozygous 677 / Homozygous 1298 (one parent passed down the 677 mutation; both passed down the 1298)
- Homozygous 677 / Heterozygous 1298 (both parents passed down the 677 mutation; one passed down the 1298)
- Heterozygous 677 / Heterozygous 1298 (Compound Heterozygous: one parent passed 677; one passed 1298)
- Homozygous 677 / Homozygous 1298 (Compound Homozygous, meaning you have two 677, two 1298)
Are you overwhelmed yet?
Testing
Dr. Amy Yasko will test about 30 methylation SNP’s (
single nucleotide polymorphisms),
here. You may need a doctor’s prescription. It is considered to be a highly accurate test.
A similar one you can do on your own with saliva…and is highly recommended and popular…is from 23andme.It is stated to miss 5 SNP’s that Yasko’s will not miss, but is cheaper and still an excellent test. NOTE: 23andme states the following:
23andme provides ancestry-related genetic reports and uninterpreted raw genetic data. We no longer offer our health-related genetic reports. That does NOT mean you won’t get what you need. After the 23andme results come back, you’ll get “raw data”. You will upload that data to any of the following, which in turn will give you what you need:
- Genetic Genie, which will look at your methylation genetics just by reading your 23andMe raw data.
- Live Wello, which gives a great deal of information to you based on 23and me, plus links to learn more about each gene’s potential problem.
- Nutrahacker will tell you what supplements you need to take, and which ones plus more you need to avoid, due to your mutations. It’s very interesting!
- Sterling Hill’s app http://www.mthfrsupport.com/sterlings-app/ or you can contact her and pay for a call to help with interpretation of your genetics.
Another informative test is the
NutrEval, which will test your antioxidants, B Vitamins, digestive support, essential fatty acids, and minerals, plus amino acids via a urine collection.
How to treat it
You can’t change a defective gene. But you can help it do its job better and minimize problems.
Some find their ‘folic acid’ lab test levels are high (it’s one of several folate vitamins) since a defect in the gene prevents your body from using it, so it goes high…unused. The recommended solution is avoid supplements and many processed foods with folic acid, especially if you are Homozygous (having a copy of the same defective gene from each parent). Healthy foods that contain folate should be okay, as would be the active form of folate called methylfolate as a supplement, also called 5-MTHF (5-methyltetrahydrofolate).
B12 might also be high, so patients tend to avoid the synthetic supplemental version of B12 called cyanocobalamin and instead favor the more useable methylcobalamin (methylB12), which will help break down those high levels. But the methylB12 will be used by your body in detoxing you from toxins, so you may need to start low to avoid detox side effects like fatigue, achiness, etc.
Another good B-vitamin is the methyl version of B6, called P-5-P.
Dr. Ben Lynch feels that
“repairing the digestive system and optimizing the flora should be one of the first steps in correcting methylation deficiency”, and that especially includes treating
candida because of the toxins it releases, inhibiting proper methylation.
Some experts recommend eating clean, such as Paleo or the
GAPS diet.
Avoiding exposure to toxins is important! Look at your household clean supplies, for example.
If adding methyl B’s cause you to over-methylate, taking time-released Niacin, 50 mg, can slow it down. Symptoms of over-methylation can include muscle pain or headaches, fatigue, insomnia, irritability or anxiety.
Minerals play a key role in several enzymatic functions. Vitamin C helps reduce oxidants. Molybdenum (500 mcg) helps break down excess sulfates and sulfites
***And here’s a REALLY NEAT website to upload your 23andme raw data to because it tells you what supplements to take and/or avoid:
https://www.nutrahacker.com/
High Copper/Low zinc
This can be a common finding when you have an MTHFR defect–a high level of copper, which will conversely mean your zinc levels will fall. And since the ratio of these two metals is highly important, correctly the problem is crucial, since high copper can be related to hyperactivity, depression, headaches, acne, frequent colds due to lowered immunity, sensitive skin and/or bruising, worsening hypothyroid, adrenal stress and more.
High copper can also make it difficult to raise iron levels, including your ferritin.
Vitamin C is known to help lower high levels of copper via detoxing, but patients report they need to go low and slow to tolerate the detoxing. Zinc is also used the same way–to encourage the lowering of copper, but the same caution with detoxing applies. Lawrence Wilson, MD recommends a nutritional approach to correcting the imbalance: remove IUD’s, avoid high copper foods like chocolate, seeds and avocados, avoid stress and
more. Work with your doctor.
Are there other mutations to be aware of?
Yes, and one is called a
CBS mutation. When doing its job correctly, the CBS gene will convert homocysteine into cystathionine, and this pathway removes sulfur containing amino acids. When it’s not doing its job correctly, you could have an excess of sulphur, which can cause kidney damage. Experts strongly recommend avoiding processed foods if you have this mutation, since they can have high amounts of sulphur. This mutation can also cause low serotonin and dopamine, and make you sensitive to chemicals.
Conversely, one can have an elevated, “up-regulated” CBS pathway, resulting in excess ammonia, urinary sulfates, and lowered breakdown of glutathione. (Janie has that one)
Real stories
Have your own story? Send it to Janie using the Contact below!
More to read
What does SNP mean??
As you get to reading about all your genes, you may see the acronym SNP used a lot (sounds like snip). It stands for Single Nucleotide Polymorphism. And SNP is basically another word for a mutation in your gene.
http://www.stopthethyroidmadness.com/mthfr/
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42 Comments
I am not a doctor nor a medical professional. Everything on this post comes from my own research and conversations with other doctors, and should not be used to diagnose or treat any illness. This is not a medical article, and citing sources is the bane of my existence, so my intent for writing this is just simply food for thought.
This post is also not meant to strike fear or worry into anyone, but rather give people who are struggling with certain health issues a possibility of healing, and an ownership of ones health.
My sources for this post come from the teachings of Dr. Neil Rawlins, Dr. Ben Lynch, Dr. Amy Yasko, Dr. Katherine Erlich, and with chat’s with my pediatrician, who promotes MTHFR testing.
Hi, I am compound heterozygous for MTHFR, which mutation do you have?
This is how I feel after spending the last month researching this extremely common, yet often undiagnosed, genetic mutation. Who would have thought something with such a funny name (my doctor referred to it as the “Monday-Thursday-Friday” mutation, hence M-TH-FR) would not only be so common, but also, possibly the cause of a monstrous slew of physical and mental issues effecting us today?
I will dive into more specifics below, but two of the main concerns of the MTHFR mutation are the following:
1. This mutation inhibits the body's ability to methylate, or convert folic acid into Methylfolate. Methylfolate is the active and usable form of folic acid, and if the body is not getting enough of this usable folate at the cell level, a dangerous cycle begins and leads to deficiency’s and a multitude of health issues.
2. Our ability to detoxify is extremely hindered. Think of a revolving door…. On a daily basis, toxins are coming in, and in a normal healthy individual, toxins are also coming out. But when you have this MTHFR mutation, toxins get trapped, and will continue to build up over the years.
MTHFR, what exactly is it?
The MTHFR gene is responsible for making a functional MTHFR enzyme (yup, in case you’re wondering, MTHFR is the name of both the gene AND the enzyme). This enzyme is a key regulatory enzyme in the metabolism of folate, and the gene itself has a very important and complex role. If the MTHFR gene is mutated, the MTHFR enzyme will not function properly.
The most common MTHFR gene mutations are found at position C677T and/or position A1298C on the MTHFR gene. There other known MTHFR variant’s, but these are the most studied. Below are the possible combinations of MTHFR gene mutation.
Heterozygous Mutation: This is the most common and less severe of all the mutations. It means you have 1 normal gene and 1 mutated gene. The mutation will either be on the 677 or the 1298 position. The MTHFR enzyme will run at about 55-70% efficiency compared to normal MTHFR enzymes.
Homozygous Mutation: This means you have 2 affected genes on either the 677 or the 1298 position. In this case, your MTHFR enzyme will only run at about 7-10% efficiency.
Compound Heterozygous Mutation: This is when you have 1 mutation on the 677 gene and 1 mutation of the 1298 gene. This combination is more severe, due to the fact that you will have symptoms of both gene defects. 98% of autistic children have the 677 and 1298 anomaly (genetic predisposition + heavy metal accumulation).When it comes to something like this, being proactive and positive is the best medicine. My children and I are taking our methylfolate everyday, eating well, and feeling great. We are actively by-passing this mutation everyday, and I have a feeling, knowing what I know now, this gene mutation isn't going to cause us much trouble in the future.
Continuing eating and living as healthy, natural, and non-toxic as I can
Make sure my diet is rich in natural folate (leafy greens, beans, citrus, etc)
Avoiding the synthetic folic acid in supplements and fortified foods, and instead, using supplements with the methylfolate and methylcobalamin.
Take blood thinning precautions during pregnancy
Continue to avoid dairy and wheat products. There has been speculation that there is a correlation between mutations on the C677T gene and an intolerance to these two foods. (Whether this is just speculation or truth, I know for a fact that I, as well as my son's, cannot tolerate either of these.)
When not pregnant, I am going to try to find way's to make sure I am sweating every week, sweating a one of the best natural way's to expel toxins from the body. (sauna, exercise, etc)
Continue juicing a few times every week, if not daily. This is great for both folate and detoxification.
And as for the gigantic list of ailments attributed with MTHFR, well, I can sit around and worry, or I can live life happily, trust God completely, and never stop learning :)
So what is the difference between the 677 and 1298 gene mutation?
Mutation 677 – This mutation is most commonly associated with heart disease, heart attack, stroke, blood clots, peripheral neuropathy, anemia, miscarriages, congenital birth defects, and more.
Mutation 1298 – This mutation is most commonly associated with chronic illnesses, such as; depression, fibromyalgia, chronic fatigue syndrome, migraines, IBS (Irritable Bowel Syndrome), Memory loss, Alzheimer's and Dementia, OCD, Bipolar, Schizophrenia, and more
Why is it associated with all these illnesses?
Methylation
The Methylation Cycle is the major biochemical pathway in our bodies that contributes to a wide range of crucial body functions, such as detoxification, immune function, mood balancing, and more. If one pathway is hindered, such as in the case of MTHFR mutations, other pathways which are reliant on it, will also be hindered. This will end up causing a “hindered” ripple effect throughout the entire body, and many of its processes, resulting in a myriad of chronic diseases.
For example, think of the body as a major highway. When one "lane" is blocked, this ties up traffic until it is fixed, or until there is a detour available. Although, many times the detour is not always efficient, and not only use more energy, but is also prone to back-ups and problems.
In the specific case of MTHFR mutations, the enzymes are responsible for converting folic acid into methylfolate, which is the active, and usable form of folate. Folic Acid is actually a synthetic form of folate, not found in nature, and unless it is converted into methylfolate, the body’s cells can’t use it. The tricky part, is that this conversion from folic acid to Methylfolate is a 4-step process, and those with the MTHFR genetic defect cannot properly complete this process, resulting in a severe lack of the ever-so-important methylfolate.
As mentioned above, when one pathway is sluggish, this creates a ripple effect, and when the body is in constant low supply of methylfolate, many other functions are affected, below are two major pathways which are affected.
1. Glutathione
When you have the MTHFR mutation, the pathway for Glutathione production is partially blocked and you have much lower levels than normal. Glutathione is the key antioxidant and detoxifier in our body, so when its production is hindered, one is more susceptible to stress and less tolerant to toxins. As we age, the accumulation of heavy metals and toxins grows, and may lead to a multitude of symptoms including disease, memory loss, rashes, premature greying hair, hair loss, social deficits, migraines, depression, anxiety, nausea, diarrhea, cancers, and more.
Also, as mentioned above, since 98% of children who are autistic have a form of this MTHFR mutation, then it seems likely there is a correlation, right? Wouldn’t it make sense that a person who cannot detoxify properly, will slowly begin to build up a dangerous load of toxins? Now, the human body is amazing, and we are pretty hardy and adaptable, some of us can get every vaccine in the book, eat a standard American diet, live right under cell phone towers, and drink tap water everyday, and not develop any major health or mental issues. But what if some of us are not so hardy due to genetic predisposition?
2. Homocysteine and Methionine
A lack of methylfolate also hinders the multi-step process that converts the amino acid homocysteine, to another amino acid, called methionine. As a result, homocysteine builds up in the bloodstream, and the amount of methionine is reduced. The body needs methionine to make proteins and many other important compounds. It also aids many processes in the body, from breaking down histamine, seratonin, and dopamine. Thus, this defective methylation pathway is associated with psychiatric illnesses, such as schizophrenia, depression and bipolar, as well as autoimmunity disorders, ADD, autism.
Another issue involving elevated homocysteine levels is called hypercoagulability, this means your blood clots more easily than it should. This is especially a cause of concern during pregnancy. As mentioned above, there are various forms of MTHFR mutations, and some will be more serious than others as far as their ability to cause problems during a pregnancy. Although still under debate, many believe that these mutations can cause blood clots between the developing placenta and uterine wall, thus preventing transport of nutrients and oxygen to the developing baby. This usually occurs early in pregnancy when the baby is most vulnerable. Many women today who experience recurrent pregnancy loss, will be tested for MTHFR.
Elevated homocycteine is also frequently found in pregnant woman who experience preeclampsia (elevated blood pressure), placental abruption (where the placenta detaches from the uterus), giving birth to a small, low-birth-weight baby (called intrauterine growth restriction), and neural tube defect (an abnormality of the fetal spine or brain). However, there is a difference of thought on whether homocysteine levels may be a consequence of these complications, or if there is a cause........ but the link is there, and extreme importance would be made to make sure homocysteine levels are normal during pregnancy, especially those with MTHFR.
MTHFR Treatment:
The normal protocol used in doctor offices today for MTHFR mutations (especially during pregnancy) is to go on a mega dose of folic acid, usually around 1+mg. As mentioned above, folic acid is a synthetic form of folate, and is added to many of today's foods, and most all multi-vitamins.
The problem with this supplementation is that, MTHFR mutations are not a “one size fits all”. Those with the mutation on the C677T location, have an especially hard time converting folic acid into methylfolate, so even though you are taking such high levels of folic acid, you body cannot use it, and folic acid is useless unless it is converted into usable methylfolte. There is also controversy over whether or not unused folic acid can potentially build up in the body, which has been suspected to stimulate pre-existing cancer cells, promote inflammation, and aid in cognitive decline
So what should you take? Since MTHFR patients are defective in the conversion process from folic acid to methylfolate, they should be given pure methylfolate, which is the already converted and usable form they are deficient in. This way the defect is "by-passed".
The tricky part when it comes to methylfoate supplementation, is the the dosing. There is no standard, and since most non-integrative doctors still prescribe folic acid, it is hard to figure out proper dosing. It is somewhat a “guess, test, and revise” approach, which is not ideal of course. The key is to start out slow in very small doses and work your way up.
I have found it interesting that now many brands of multi-vitamins made especially for children with autism, will not contain folic acid, but rather methylfolate. So the connection is being recognized. There are also a few prenatal vitamins formulated in a similar manor, (such as Thorne Prenatal), since MTHFR mutations have been linked to repeat miscarriages.
Personal Experience
I was diagnosed about 5 years ago after we lost our precious son when I was 9 months pregnant, (you can read about our sad AND happy journey in my post A New Set of Eyes). I then received the news that not only did I have Factor V Leiden, but that I was also compound heterozygous for MTHFR. I was put on 1 mg of folic acid, and when I became pregnant, I used daily Lovenox injections and a baby aspirin. Since then, I have had 3 easy pregnancies and 3 amazing little boys. So….. part of me thinks, it worked! I will just use the above cocktail every time I get pregnant, and all is well in my world.
Well, then a couple months ago, I had to go and ruffle my feathers. I had been experiencing some unpleasant symptoms for roughly 10 months, and I was trying my darndest to figure out what was causing them. I was not sure where to start, but I knew I had this MTHFR gene defect, so I thought I would begin there. Could this be causing my problems?
Eureka! About 4 weeks ago, I figured out my symptoms were wheat related, and now that I am 100% off gluten/wheat my symptoms are 99% gone, (but that is a different story for a different time).
The damage was done. During those 4 weeks, I was researching MTHFR with every free minute I had. My mind was a roller coaster. I had no idea how major MTHFR was! My little happy world all of a sudden became a scary place with so many questions.
Is this why my sons and I have so many food intolerance's and allergies?
Are they susceptible to autism?
Am I one toxic mess?
What if I get pregnant again?
Do I take folic acid or methylfolate?
Agh, too many questions, and such a lack of answers. Then my mom brought me back to reality. “Meg, instead of going straight to the computer and diving deeper into your worries, you go straight to God first and trust in Him to take care of this”.
Bingo.
Why are mom’s always right? Looking into this stuff is scary, the internet is scary……. but ultimately we just have to be educated, live as healthy as we can, stop worrying, and trust completely in God in every circumstance.
So since my conversation with my wise mother, I am learning that this gene mutation is more empowering, than it is scary. I have learned so much, and feel confident that I have a great understanding on the best diet, the healthiest way of life, and the most useful supplements for my condition. I also got my children tested ( which came back positive for homozygous and compound heterozygous mutations), and my husband’s will be tested soon as well.
So what am I doing to control my compound heterozygous mutation?
Comments with thoughts, questions, and disagreements are welcome. I am hoping this post will be a learning experience for myself and all the readers. (just please keep them respectful :)
Here is an informational pamphlet by Thorne, containing valuable research regarding MTHFR.
This is an AMAZING and (long) article by Dr. Amy Yasko. It ties the whole methylation cycle together. (did I mention that this was amazing?)
Below is a 51 minute lecture by Dr. Neil Rawlins, which is broken up into 4 parts. I have found this to be exceptionally helpful and would be a great starting place for anyone looking for more information. https://www.youtube.com/watch?v=ZA8GUIRqIkE
http://www.freshideamama.com/mthfr-since-40-60-of-the-population-has-this-condition-and-it-is-the-underlying-cause-for-many-chronic-illnesses-shouldnt-we-all-be-getting-tested
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Methylfolate Makes Me Crazy
We’ve talked about the MTHFR mutant problem before (
right here) but haven’t really addressed the actual taking of methylfolate. We mutants are out there, walking among you unable to convert regular old folic acid into methylfolate. I will stand with pride among you my brothers and sisters because yes, I too am a mutant. Deep shuddering sigh. As it turns out, using gene markers alone to plan a healthy nutritional protocol is not as straightforward as it would seem. The reason being that every system in the human body has a glorious level of redundancy – we are literally designed to fail in eight hundred ways and still function normally.
Simply having the MTHFR mutation doesn’t actually mean that high-dose methylfolate like Deplin® which is prescribed in either 7.5 mg or 15 mg doses is a good idea. The reason for this is that your body has literally hundreds of overlapping systems that are involved in every function that is even remotely related to the ways you use folate in the body. These overlapping systems and layers of function help our body to function normally even with multiple mutations that may result in genuinely low levels of methylfolate. Obviously that’s awesome when you don’t have methylfolate, but it can be a little overwhelming when all of a sudden you have a ton of it.
5-MTHF – One of my favorite methylfolate supplements
Picture flooding your system with methylfolate when there has been relatively little (and when your body has been functioning reasonably normally with relatively little). Your cup literally runneth over. In some cases your body has been starving and so it’s a welcome relief like rain in the desert – all functions get better and you’re ridiculously glad to have some resources to work with. In other cases the flood of methylfolate is literally a flood and you’re stuck trying to clean up the mess.
Side Effects of Methylfolate:
- Mood changes: depression, irritability, severe anxiety
- Pain: sore muscles, joint aches, headaches, migraines
- Physical Symptoms: rash, acne, heart palpitations, nausea, insomnia
You will notice that some of these side effects are exactly the symptoms we’re looking to fix by taking the methylfolate, which seems a little ironic and inconvenient. Such is the way of medicine, no? Like the drug you take for constipation that may cause constipation. Thankfully here the benefits far outweigh the risks, you just have to know how to do it right. Remember that methylfolate is something your body actually needs, so it’s important to find a way to take it well.
Avoiding Methylfolate Side Effects:
- Start slow: Some people with the MTHFR mutation have no trouble taking methylfolate and feel a world of difference from it. For the rest of us it’s a little too much, a little too quickly. If that is you then backing the dose way down to what might be in a good multivitamin (400 – 800 mcg) is a great way to start. From there you can slowly adjust your dose to find your own optimal dosage level.
- Personalize: When we’re talking about your genes it really is all about YOU. Just because something works for lots of people with the MTHFR mutation doesn’t mean it will work for you, so above all trust your body and your symptoms. If you’re having a problem doing something one way (even though that way works for your doctor or your neighbor or everyone else on a forum) trust that and change your strategy.
- Pulse Your Dose: For some people it helps to have some days on and some days off, meaning to take methylfolate at whatever dose your body can tolerate for some days but not others. For my body personally the best strategy I’ve found so far is taking lower doses five days per week and taking weekends off (convenient too!) For some of my clients it’s a week on/week off plan at a higher dose. This really does come down to experimenting with your body to find what is right for you.
- Expect Some Adjustment: Remember that your body has been compensating for all of your mutations for as long as you’ve been alive so suddenly changing the entire playing field is bound to create a few waves. Before you make a snap judgement about what works for you and what doesn’t give things a few days to calm down. Your body will constantly astound you with it’s flexibility, it’s adaptability and it’s ability to cope with ridiculously huge changes but even your miraculous body may take a couple of days.
- Niacin to the rescue: 50 – 100 mg of time-release niacin can be incredibly helpful to counteract some of the side effects of methylfolate if an alternative dosing plan isn’t enough to make you feel awesome. Niacin helps your body to use excessive SAM (S-adenylmethionine) which can build up in some people taking methylfolate. It’s important to also experiment with your dosing to find the right level of niacin for you, and in larger doses niacin, even in it’s time-release form, can cause flushing.
- Antiinflammatories: Some of the problem is just basically that your body was probably inflamed going into the methylfolate therapy and changing your protocol can stir everything up. Also by taking methylfolate you are allowing your body to start to catch up on detoxification and repair, which can also increase your level of inflammation while everything is being sorted out. Good strong natural anti-inflammatories can help to decrease symptoms and help your body to adjust, especially while you’re finding your optimal dosage. A lipid-soluble form of curcumin (from turmeric) like Meriva® can make your life far easier. Other great natural anti-inflammatories include fish oils, green tea, pycnogenol, boswellia, resveratrol and cat’s claw. Following an anti-inflammatory diet is tremendously helpful as well.
- Hydroxycobalamin: In an odd twist this non-methylated form of vitamin B12 can help to control some of the side effects of methylfolate as well. One of the benefits of taking methylfolate is that it increases your levels of nitric oxide, which is the signal that helps your blood vessels dilate. Which is exactly why it helps with cardiovascular risk and headaches and lots of the other things it helps with. Like with everything else in life, too much of a good thing is sometimes a really bad thing. So if your nitric oxide levels end up becoming too high then your body starts to make free radicals, and those free radicals create side effects. Hydroxycobalamin can help you to counter this effect. Again, experiment with your dosing.
Remember that if you have MTHFR mutations then your body will function better on so many levels by getting the methylfolate that you’ve literally been starving for, so it’s worth it to find the right dose and the right way of taking methylfolate for you. This can save you from heart disease, stroke, heart attack, periodontal disease, anxiety, insomnia, depression, mood disorders, reproductive problems, even birth defects in your children. It’s important, so it’s important to know how to do it right.
http://dramyneuzil.com/methylfolate-makes-me-crazy/
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How Much Methylfolate Should I Take? Find Out
When one is diagnosed with a MTHFR mutation, the first thing typically prescribed is methylfolate – or, incorrectly, folic acid in high amounts.
There is no standard of care prescribing methylfolate for MTHFR mutations. Thus, the variation in prescriptions is vast – anywhere from nothing done upwards to Deplin 15 mg or Folic Acid 4 mg.
There are a few issues here:
- Doctors are guessing how much methylfolate to give you
- Doctors are giving high doses of methylfolate
- Doctors should not prescribe high dose folic acid
- Diet is commonly not evaluated
- Supplements are commonly not evaluated
Even with all these issues, doctors – and you – can know how much methylfolate you should take.
There is a lab test which evaluates blood levels of:
- unmetabolized folic acid
- methylfolate
If doctors order this lab test, methylfolate dosing will be more accurate.
There are a couple potential issues with the lab test.
- Is methylfolate stable or does it readily break down thus making the lab results inaccurate?
- Where did the lab get the normal ranges for methylfolate? Since the general population has a 50% to 60% chance of having one MTHFR mutation, the potential for methylfolate ‘normal’ ranges being off exists.
These are two questions that need to be asked – and will be followed up here.
In the meantime, for those wanting to evaluate their unmetabolized folic acid levels and methylfolate levels, I do recommend ordering the Unmetabolized Folic Acid Test by Metametrix. [Please note: Metametrix (now Genova Diagnostics) has discontinued the Unmetabolized Folic Acid Test as of January 16, 2015.]
Who should order this test?
Where do I send my doctor to order this test for me?
You send them to
Metametrix.
Stop guessing and identify if your methylfolate levels are where they should be.
Be sure to tell your doctor about this test!
Don’t Want to Pay for a Lab Test? Rather experiment to see how much Methylfolate you need?
If you have been diagnosed with a MTHFR defect, and you want to try taking some methylfolate, what I recommend trying to do is this:
- Take small amounts of methylfolate along with methylcobalalmin and work up.
- Consider taking 1/2 tablet of Active B12 with Methylfolate. This amount is typically well-tolerated by many.
- Increase to a full tablet after 1 week.
- Continue to increase the amount taken by 1/2 tablet every 7 days until you feel really good.
- If you feel side effects from taking Active B12 with Methylfolate, take 1/10th tablet of Niacin.
- Work with your doctor on this and inform them what you are doing.
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L-Methylfolate, Methylfolate, 5-MTHF, L-5-MTHF. What is the Difference!?
Those with MTHFR mutations scan labels, read websites or listen to their doctors rattle of conflicting terms for a nutrient they really need.
Understanding which form of methylfolate is best must be clear.
Why all the confusion?
Because there are so many different terms used for methylfolate.
By the end, you will understand everything you need to know about methylfolate.
More significantly – you will understand how to pick the right form of methylfolate.
Terms often used for methylfolate are:
- Methylfolate
- L-MTHF
- L-Methylfolate
- L-Methylfolate Calcium
- D-Methylfolate
- D-5-Methylfolate
- Levomefolic Acid
- Metafolin
- 5-MTHF
- 5-Methylfolate
- 5-Methyltetrahydrofolate
- L-5-MTHF
- L-5-Methyltetrahydrofolate
- 6(S)-5-MTHF
- 6(S)-5-Methyltetrahydrofolate
- 6(R)-5-MTHF
- 6(R)-5-methyltetrahydrofolate
- Quatrefolic
Are these forms of methylfolate all the same?
No.
Are any of these forms of methylfolate the same?
Yes. The same forms are grouped together here. These forms are synonymous with each other:
- L-5-MTHF = L-5-Methyltetrahydrofolate = 6(S)-L-MTHF = 6(S)-L-Methyltetrahydrofolate
- Good forms which are well absorbed
- L-Methylfolate Calcium = Metafolin = Levomefolic Acid
- Good forms which are all well absorbed
- D-5-MTHF = D-5-Methyltetrahydrofolate = 6(R)-L-MTHF = 6(R)-L-Methyltetrahydrofolate
- Avoid these (learn why soon…)
Then what are the other forms of methylfolate?
The other forms of methylfolate may or may not be 99% pure biologically active methylfolate.
- 5-MTHF
- 5-Methylfolate
- 5-Methyltetrahydrofolate
How come these may or may not be 99% pure biologically active methylfolate?
These forms do not specify the L form (or 6(S) form) of methylfolate; therefore, you do not know what you are ingesting.
The forms of methylfolate not specifying L or 6(S) likely contain more than 1% of the D form of methylfolate.
What is the difference between D and L forms of Methylfolate?In organic chemistry, one learns compounds may have the exact same molecular formula and sequence of bonded atoms but differ three dimensionally. These compounds are known as steroisomers.[
1]
There are two common forms of sterioisomers:
- Enantiomers:
- mirror images of each other, such as our hands.
- same physical properties
- may have different biological effects
- Diastereoisomers:
- not mirror images of each other
- rarely have same physical properties
- have different biological effects
Methylfolate has stereoisomers in the form of diastereoisomers.
The forms of methylfolate that are biologically active are:
- L forms
- 6(S) forms
- L-5 forms
- Metafolin
- L-Methylfolate Calcium
- Levomefolic Acid
- Quatrefolic
The forms of methylfolate that are NOT biologically active are:
The forms of methylfolate that may or may not be biologically active are the:
- forms which do not specify L, 6(S) or trademarked name of Metafolin
- 5-MTHF
- 5-methylfolate
- 5-methyltetrahydrofolate
From the package insert of Metanx, a prescription drug using biologically active Metafolin[2]:“L-methylfolate or 6(S)-5-methyltetrahydrofolate [6(S)-5-MTHF], is the primary biologically active diastereoisomer of folate and the primary form of folate in circulation. It is also the form which is transported across membranes into peripheral tissues, particularly across the blood brain barrier. In the cell, 6(S)-5-MTHF is used in the methylation of homocysteine to form methionine and tetrahydrofolate (THF). THF is the immediate acceptor of one carbon units for the synthesis of thymidine-DNA, purines (RNA and DNA) and methionine. About 70% of food folate and cellular folate is comprised of 6(S)-5-MTHF. Folic acid, the synthetic form of folate, must undergo enzymatic reduction by methylenetetrahydrofolate reductase (MTHFR) to become biologically active. Genetic mutations of MTHFR result in a cell’s inability to convert folic acid to 6(S)-5-MTHF.
Metafolin® (L-methylfolate calcium) is a substantially diastereoisomerically pure source of L-methylfolate containing not more than 1% D-methylfolate which results in not more than 0.03 milligrams of D-methylfolate in Metanx®
D-methylfolate or 6(R)-5-methyltetrahydrofolate [6(R)-5-MTHF] is the other diastereoisomer of folate. Studies administering doses of 2.5 mg per day or higher resulted in plasma protein binding of D-methylfolate higher than L-methylfolate causing a significantly higher renal clearance of L-methylfolate when compared to D-methylfolate. Further, D-methylfolate is found to be stored in tissues in the body, mainly in the liver. D-methylfolate is not metabolized by the body and has been hypothesized to inhibit regulatory enzymes related to folate and homocysteine metabolism and reduces the bioavailability of L-methylfolate.”
Example of why all this is important to know
A supplement company has a supplement called, “5-MTHF”
Let’s say this supplement states it contains 10 mg of 5-MTHF.
One assumes this contains 10 mg of biologically active L-methylfolate.
Don’t assume.
The likelihood of it containing 99% of the biologically active form of L-methylfolate is slim to none.
Why?
Prescription drugs such as Deplin contain 99% active L-methylfolate as Metafolin. Deplin provides two potencies of L-methylfolate: 7.5 mg and a 15 mg
This much L-methylfolate is VERY potent and must be prescribed by a physician.
Merck does not allow any supplement company to provide more than 1 mg of their L-methylfolate in a stand-alone supplement. If L-methylfolate, as Metafolin, is included in a formula along with other nutrients, then a maximum of 800 mcg is allowed.
What amount of this 10 gram 5-MTHF supplement actually contains the biologically active L-methylfolate?It is not known without requesting a lab report.
The likelihood of it containing a significant amount of the inactive D form of methylfolate is high.
Remember, the D form of methylfolate is undesirable and actually may reduce the bioavailability of L-methylfolate.
What to do?Two things:
- Request a prescription from their physician to obtain drugs containing Metafolin.
- Look for supplements specifying the amount of active L-methylfolate.
Drugs containing Metafolin are:
- Metanx
- Deplin
- Cerefolin
- CerefolinNAC
- Neevo
- NeevoDHA
Supplements with Methylfolate
One must carefully evaluate supplements specifying the use of Metafolin, Quatrefolic or the L form.
If the supplement does not specify on the label that it uses Metafolin, Quartrefolic or the L form of methylfolate, then it is not recommended to use without first inquiring directly to the manufacturer. A manufacturer may have named their product as 5-MTHF and use the pure L form of methylfolate; however, one must inquire to be certain.
Quatrefolic: What is this?
This is a new form of methylfolate that uses glucosamine instead of calcium to bind the L-methylfolate. Quatrefolic is also a quality form of L-methylfolate.
Key Points about Methylfolate:
- Not all methylfolate is the same
- The D form of methylfolate actually is undesired and should be avoided
- The L form of methylfolate is the desired form
- There are many names for the same thing. Understand them.
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Supplements using the pure form of L-Methylfolate
Seeking Health uses purely the L-methylfolate as Metafolin.
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Advice found on a FB feed.....
need to vet it, but it's pretty damned specific.
If you have the 1298 MTHFR variation you will need to pay extra attention to aluminum for one thing, and C677T will require more attention to folate. Glutathione is often low in these people too so they will need extra support to get methylation pathways moving. Too much too soon can overload their ability to detoxify. Methylation protocols can be tricky due to the effects of current levels of toxins and other genes that interact. But a solid base of active b''s, green drinks, adequate b12 levels, good iron levels (too much or too little is an issue), thyroid levels must be good and so must cortisol levels (too high or too low is not good and will slow the methylation process and hamper detox)..
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from Jason:
Make sure to read each of the following links very carefully.
MTHFR genetic defect – what it is and how it can affect you
http://www.stopthethyroidmadness.com/mthfr/
MTHFR Research
http://mthfr.net/mthfr-research/2012/01/27/
Approaches to Supplementing for MTHFR Including the Right Type of B12
(Note: No matter what kind of B12 and folate you need, beginning with Garden of Life's B complex is still something that I would suggest because that's the most natural B complex there is.)
http://mthfrliving.com/health-tips/supplementing-for-mthfr-b12/
What is the MTHFR Genetic Defect and How Can it Affect You?
http://www.globalhealingcenter.com/natural-health/what-is-the-mthfr-genetic-defect/
