MTHFR genetic mutation – what it is and how it can affect 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 MTHFR gene, aka methylenetetrahydrofolate reductase was defective in a lot of folks worldwide! Some state more than 60% (and yes most of us end up calling it the dirty word gene–lol).
i.e. this gene when working correctly helps break down needed metals for use in your body….like iron, or B12, or other nutrients. Additionally, it helps down excess metals and toxins to be removed from your body. So when it’s not working correctly, meaning the mutation is activated, you might see elevated levels of iron, or B12, or heavy metals…or a family history of heart problems or cancers to name a few, because those heavy metals and toxins aren’t being eliminated from the body.
When it’s all working right (and it can be for awhile even with the mutation), the MTHFR gene begins a multi-step chemical breakdown process, aka methylation, which 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 will eliminate toxins and heavy metals, which can reduce your risk for cancer, heart disease and other health issues, and put less stress on your adrenals.
But here’s what an activated MTHFR mutation 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, causing a higher risk for issues like heart problems, cancers, miscarriages, etc. i.e. you could find yourself with high iron, or high copper, or high lead, or high mercury, or high uranium…it varies from person to person. Each person with the MTHFR mutation may have different metals which are high.
- A way to see what metals might be high is ordering this hair test (3rd one down on the list): https://www.directlabs.com/sttm/OrderTests.aspx (if the latter link doesn’t work for you, copy and paste it, but take out the “s” after http)
- The defective enzyme (especially 677) doesn’t break down folate vitamins properly (of which folic acid is the precursor to, but we take folate instead), 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 can be poorly converted to glutathione, which is your body’s chief antioxidant and detoxifier. You are then more susceptible to stress and toxin buildup.
- Homocysteine can be 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 activated mutation can increase your risk of a variety of cancers (including breast and prostate cancer), stroke, various 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. And you know what is seen a lot in groups? High B-12 with low folate, or low folate with high B12. It’s all very individual. And not that having B12, for example, can result in low B12 symptoms….
- 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)
- People often notice they have a family history of heart problems or cancers when this mutation is being passed down.
Two important MTHFR gene mutations with different combinations
The two most problematic MTHFR methylation mutations are called 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. Genes are passed down by your mother and your father. Most literature states there are a good 40-50 different mutations of this important methylation ene which could be passed down by one, or both or your parents.
There are many combinations of MTHFR methylation mutations:
- 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 heterozygous 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?
Dr. Ben Lynch states that being homozygous A1298C or compound heterozygous MTHFR means there is a high chance the mutation is being strongly passed down via your your family members who also have the problem.1.
Janie Bowthorpe has noticed that even simply having one mutation with A1298C can eventually start expressing itself, especially as our bodies age.
1. The most definitive way to find out is genetic testing. And a popular self-ordered test comes from 23andme. Plus a bonus: you get a LOT more genetic and ancestry information.
After the 23andme results come back, you’ll get “raw data” that you won’t be able to read well. You will upload that data to any of the following, which in turn will give you what you need:
- 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. Do use the Search bar to see if you have other mutations you hear about. Janie Bowthorpe loves this one and highly recommends it.
- Genetic Genie, which will look at your methylation genetics just by reading your 23andMe raw data.
- Nutrahacker.…though it doesn’t interpret the raw data the way Live Wello does above, 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.
2. Another clue is to do hair testing. Direct Labs has a hair test you can order on your own. Though genetic testing above is a must, it’s always interesting to see what heavy metals are not being broken down because of the MTHFR mutation, plus gives you a baseline to refer to later to see if your treatment is working.
3. 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, but can be more expensive than the more popular 23andme test above.
A vast amount of genetic information can be obtained from www.promethease.com
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. Expensive, but oh to informative.
Part Two: there are other methylation-related gene mutations that can need attention even before you treat an MTHFR mutation
i.e. after doing 23andme and uploading to a website like livewello.com, there are methyl-related genes you need to look into.
- CBS: 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. Some people with a CBS mutation can seem to feel with with the version of B6 called P5P, so they have to start much lower. 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)
- SUOX: When working correctly, this gene oxidizes sulfite to sulfate. If this gene has a mutation, it can mean you have inadequate levels of molybdenum and can have reactions to foods which are rich in sulfur/sulfites. i.e. like CBS, your can have too high levels of sulphur.
- MTRR and MTR: A mutation with MTRR affects your B12 negatively. An MTR mutation affects our folate negatively. And both B12 and folate are needed for good methylation….(Janie as the MTRR mutation)
- COMT, MOA-A and MOA-B: Mutations here can negatively affect how your body responds to stress, which in turn can negatively affect your methylation.
There are others which you will see on your 12andme genetic results. More info here.
How to treat it all
You can’t change a defective gene. But you can help it do its job better and minimize problems.
It’s strongly recommended to avoid folic acid supplements and in foods, and instead favor folate in supplementation, especially if you are homozygous MTHFR (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). But we need to start low, such as 400 mcg or less. You don’t want to methylate too fast.
B12 might also be high due to an active MTHFR mutation along with an active COMT mutation, so patients tend to avoid the synthetic supplemental version of B12 called cyanocobalamin and instead favor the more useable hydroxycobalmin (hydroxyB12), either which will help break down those high levels. Some use the methylcobalamin (methylB12), but for some, it can cause problems. So for many, the hydroxy form of B12 is favored as being safer until one is able to tolerate the methyl version of B12. Most need to start low to avoid detox side effects like fatigue, achiness and more. Again, all the latter is simplified and you will need to seek more detailed information from a qualified practitioner or even some of the excellent website and forums on MTHFR.
Another good B-vitamin is the methyl version of B6, called P-5-P...but again, it’s important to start low and build in low amounts. Due to certain methyl snps, not everyone tolerates it well unless it’s low.
Dr. Ben Lynch feels that “repairing the digestive system and optimizing the flora should be one of the first steps in correcting methylation deficiency”2, 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 cleaning supplies, for example, or toxic glues you may be using, and more.
**If adding methyl B’s cause you to over-methylate, taking time-released Niacin, 50 mg can slow it down, say some experts. 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 from the CBS and SUOX active mutations.
It is very, very important to avoid high stress and/or quit pushing yourself, as stress can negatively affect your body’s ability to remove toxins.
This website http://www.knowyourgenetics.com/ offers suggestions on how to treat your defects.
***And here’s an excellent website to upload your 23andme raw data to because it tells you what supplements to take and/or avoid: https://www.nutrahacker.com/
Again, all the above is simplified and working with a knowledgeable practitioner will give you the right details.
High Copper/Low zinc
This can be a common finding when you have an MTHFR defect (or other methylation snps)–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, correcting the problem is crucial, since high copper can be related to hyperactivity, depression, fearful ruminating thoughts, 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, or keep those levels where they should be.
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.
Check out information from Janie and Elaine about having had high copper and how they detoxed it: //www.stopthethyroidmadness.com/2016/08/01/high-copper/
Note: you can have high copper/low zinc without the cause being MTHFR.
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.
NOTE FROM JANIE BOWTHORPE: I have one copy of the 1298 MTHFR mutation and never had a problem, until the stress of mold exposure followed by having to detox high copper seemed to make it come alive, along with mutations with COMT, MTRR and more. My B12 suddenly went sky high, yet I had classic symptoms of low B12–it wasn’t being broken down for use. My solution was to move from methyl B12 to hydroxy B12. Took several weeks to feel the affect. I also have to be on folate.
Read Mary’s story.
Have your own story? Send it to Janie using the Contact below!
More to read
A map of all the possible methylation pathways.
Dr. Ben Lynch’s MTHFR website with forums, too.
National Library of Medicine MTHFR information page
Informative MTHFR Support website— Also has forum.
Detailed notes this mother took about MTHFR and methylation from a Dr. Ben Lynch lecture.
Other gene mutations like CBS that need to be addressed before getting too serious with MTHFR