When you have an autoimmune disease like I do, you get to learn a whole new language when it comes to your health. Terms like TSH, flare, leaky gut, and triggers become part of your vocabulary. One term that I’ve gotten many questions about lately and that deserves the attention it is finally getting is the MTHFR mutation.
What Is MTHFR?
MTHFR is an enzyme that adds a methyl group to folic acid to make it usable by the body. The MTHFR gene produces this enzyme that is necessary for properly using vitamin B9. This enzyme is also important for converting homocysteine into methionine, which the body needs for proper metabolism and muscle growth and which is needed for glutathione creation . The process of methylation also involves the enzyme from the MTHFR gene, so those with a mutation may have trouble effectively eliminating toxins from the body.
The genetics home reference offers more detail:
The MTHFR gene provides instructions for making an enzyme called methylenetetrahydrofolate reductase. This enzyme plays a role in processing amino acids, the building blocks of proteins. Methylenetetrahydrofolate reductase is important for a chemical reaction involving forms of the vitamin folate (also called vitamin B9). Specifically, this enzyme converts a molecule called 5,10-methylenetetrahydrofolate to a molecule called 5-methyltetrahydrofolate. This reaction is required for the multistep process that converts the amino acid homocysteine to another amino acid, methionine. The body uses methionine to make proteins and other important compounds.
Contrary to how it looks, “MTHFR” is not an abbreviation for a popular curse word, but a shortened form of methylenetetrahydrofolate reductase… Aren’t you glad it is abbreviated?
I touched on the importance of the MTHFR enzyme briefly in my post about folic acid vs. folate and why I am careful to avoid synthetic folic acid in supplements and foods.
Those of us with a MTHFR gene mutation have a highly reduced ability to convert folic acid or even folate into a usable form. Research estimates that as much as half of the population may have an MTHFR gene mutation, though there are many variations of the mutation, depending on how the gene was passed down from the parents. More on that below.
Problems From an MTHFR Gene Mutation
Dr. Izabella Wentz explains how the MTHFR mutation can affect those who have it:
Individuals with low activity of the MTHFR enzyme may present with elevated homocysteine levels, which have been associated with inflammation and heart disease, birth defects, difficult pregnancies, and potentially an impaired ability to detoxify.
Nutrient deficiencies in Folate, B6 and B12 have been associated with elevated homocysteine.
Individuals with the MTHFR gene actually have a difficult time processing folic acid that is present in most cheap supplements and added to processed foods. Some professionals claim that this type of folic acid may even cause a build-up in the body leading to toxicity. Studies have been done that showed folic acid supplements increased cancer risk… one more reason to ditch processed foods and your multivitamin!
Some naturopathic doctors like Dr. Doni Wilson suspect that lingering fatigue, fogginess, anxiety, sleep issues and inability to deal with alcohol and other toxins effectively can be a result of an underlying gene mutation like the MTHFR mutation. She explains how this affects many aspects of health and how stress is a compounding factor:
Activated folate (named 5MTHF) goes on to give its methyl group to other nutrients and substances – a process called “methylation.” It is required for the creation of every cell in your body, so if it is not activated properly, you can imagine what a significant issue it would be. 5MTHF, along with several other nutrients, is also used to create and process neurotransmitters (messengers in the nervous system like serotonin, epinephrine, norepinephrine, and dopamine); create immune cells and process hormones (such as estrogen); as well as to produce energy and detoxify chemicals.
Stress, in all its forms, inhibits this “methylation” – the transfer of methyl from 5MTHF to other substances. So when you are under stress, it is especially important to provide the nutrients necessary for these processes.
To clarify in more detail, the liver is a major processing system, involving countless enzyme pathways, including methylation, which turn one nutrient into another and toxins into non-toxins, preparing them all to be used and/or expelled by the body. When you drink alcohol, it is your livers job to process it using methylation, but if your nutrients are depleted or you are stressed, your liver will not be able to complete the process effectively, leading to symptoms associated with a hangover.
Identifying a potential MTHFR defect is especially important for women of childbearing age, as this defect can increase the risk of many problems in an unborn child, including folate related disorders like Spina Bifida.
Types of MTHFR Mutation
There are many different possibilities when it comes to MTHFR gene mutations and science is still working to understand them all. I’ve included links to more in-depth resources below, but there are several common mutations that can occur.
The reason for all the types of mutations is variations in the specific genes passed on from each parent. In other words, if both parents pass on a healthy gene, a person won’t have a mutation at all. If one parent passes on a healthy gene but the other passes on a mutated gene, several variations can occur. If both parents pass on a mutated form, there are many more scenarios that can occur.
The two most problematic mutations that can occur are C677T and A1298C, which denote the placement of the mutation on the gene. The most common forms of MTHFR mutation involve various combinations of these genes being passed on from each parent:
- Homozygous: the same gene passed on from both parents- can occur if both pass on the 677 mutation, or the 1298 mutation.
- Heterozygous: one parent passed on the 677 mutation or the 1298 mutation but the other parent passed on a normal gene.
- Compound Heterozygous: one parent passed on the 677 mutation and the other passed on the 1298 mutation.
- Other more advanced and rare mutations.
What Happens When the MTHFR Gene Is Defective?
Those with a defective MTHFR gene have an impaired ability to produce the MTHFR enzyme (estimates range from 20%-70% or more). This can make it more difficult to break down and eliminate not only synthetic folic acid but other substances like heavy metals.
Since folic acid can’t be converted into the usable form, it can build up in the body, which can raise levels of homocysteine. High homocysteine levels are associated with a higher risk in cardiovascular disease. This also affects the conversion to glutathione, which the body needs to remove waste and which is a potent antioxidant.
In short, we are just learning the extent to which this can affect health, but there is strong evidence that because of the affect on methylation, it can increase cancer risk, cardiovascular disease risk, risk of fetal development problems and more. It can also possibly contribute to or exacerbate other problems like autoimmune disease, mental issues and more.
How to Get Tested for MTHFR Gene Defects
Though there are many symptoms that can be associated with an MTHFR defect, the symptoms can vary widely from person to person and only a test (blood or saliva) can verify a gene defect and the type.
Janie at Stop the Thyroid Madness compiled a great list of ways to get tested. Local doctors are able to run these tests as well, but not all doctors are well-versed in handing MTHFR issues…
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:
23andmeprovides 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 mthfrsupport.com/sterlings-app or you can contact her and pay for a call to help with interpretation of your genetics.
A VAST amount of genetic information can be obtained from Promethease.com
Here’s a good string about testing methyl pathways vs genome testing.
I personally have experience with Spectra Cell tests.
MTHFR Tips
Though it isn’t possible to change a gene, there are things that can be done to minimize the potential for problems or to help avoid problems in children (before and during the mother’s pregnancy). As I said, the research is still developing on this, but some things that I find personally helpful are:
- Focusing on gut health: Especially when the body has impaired ability to use certain nutrients, it is important to focus on gut health so that the body can absorb the nutrients from food as effectively as possible. I personally avoid antibacterial soaps, vegetable oils, processed grains and refined sugars and support my gut with fermented foods and homemade broth. This also helps avoid candida, which can make MTHFR related problems worse.
- Avoiding environmental toxins as much as possible: Those with an MTHFR gene defect have an impaired ability to eliminate toxins. I avoid plastics, chemicals in beauty supplies and cleaning products, and scented candles, which can all release harmful chemicals. We use houseplants and other methods of cleaning our indoor air, and filter our drinking and shower water.
- Not taking anything with Folic Acid: As I explained in this post, folic acid is the synthetic form of folate that cannot be used by those with a MTHFR defect and which can be very toxic. I avoid any supplements with folic acid and only take L-MTHF forms, which are the methylated forms that my body can use. I also take a methyl-B12 which is supposed to help the body use L-MTHF.
- Lots of Leafy Greens: According to Dr. Ben Lynch, dark leafy greens contain the methylated forms of folate that those with a gene defect need. As if we needed more reasons that it is important to consume green veggies… I try to work in green veggies at every meal.
- Avoid Processed Foods: Again, as if anyone needed another reason to avoid processed foods… Many processed foods have synthetic folic acid added.
- Avoiding things that can block or deplete folate levels: Certain medications, including hormonal contraceptives can interfere with folate levels, and medicines like antacids can interfere with B-12 absorption.
- Avoiding Heavy Metals: Heavy metals in diet or environment are harder to remove from the body for those with a gene defect, so I’m careful to avoid these.
- Help a Body Out: Since those with a MTHFR defect have an impaired ability to eliminate toxins, I do things to help support my body in this process, such as: detox baths, sauna use, drinking enough water, dry brushing my skin and exercise (sweating). I also do strange things like using detox mud shampoo, detoxing my pits, and foot soaks.
MTHFR Video
This video with Dr. Alan Christianson and Dr. Ben Lynch provides lot of detail about MTHFR and how it affects health.
Additional Resources
If you are new to MTHFR and feel overwhelmed like I did, here are some great resources:
- Everything on mthfr.net
- What is MTHFR and why is it significant for your health? from Metabolic Healing
- What is the MTHFR genetic defect from Global Healing Center
- Stop the Thyroid Madness on MTHFR
- 29: Methylation Problems & Gene Mutations
- 97: OB & Midwife Aviva Romm on PPD, Thyroid Problems, & MTHFR
- 135: Understanding Genetic Testing, Epigenetics & Genetic Polymorphisms with Dr. Ben Lynch
Have you ever been tested for MTHFR? Please share your experience to help others!
This article was medically reviewed by Dr. Scott Soerries, MD, Family Physician and Medical Director of SteadyMD. As always, this is not personal medical advice and we recommend that you talk with your doctor.
Sources:
https://pubmed.ncbi.nlm.nih.gov/11683544/
http://primarypsychiatry.com/the-role-of-l-methylfolate-in-depressive-disorders-commentary/
https://www.bmj.com/content/328/7455/1535
http://primarypsychiatry.com/l-methylfolate-methylcobalamin-and-n-acetylcysteine-in-the-treatment-of-alzheimeras-diseasearelated-cognitive-decline/
https://pubmed.ncbi.nlm.nih.gov/22492374/
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Hi Katie,
Thanks for this post! Do you think mthfr is an underlying cause of morning sickness? I have had 4 pregnancies all with morning sickness (which has improved as my diet improved over the years). I notice that if I focus on detoxification (lemon water in morning, raw milk throughout the day, Epsom baths and turmeric) my MS is better. I am convinced that for me MS is my due to my inability to detoxify the massive amount of hormone. I also noticed that just prior to starting the GAPS diet (when my gut health was at its worst) I would get a “hangover” every time I ate gluten. I always chalked it up to liver weakness. Now I wonder if it is due to mthfr mutation? …
Hello Megan,
Is MTHFR your problem? Maybe, maybe not. There are several genes involved in the methylation cycle and its branches. Maybe a better question is whether the methylation cycle is affecting your health. That I would say is very possible. A good history, some basic hormonal or nutritional testing, and maybe genetic testing would help to answer that question. On the other hand, your improved nutrition is definitely a part of less morning sickness.
Blessings,
Eric Potter MD
Wholistic healthcare for the glory of God.
Eric, love your approach….to God be the Glory! Where do you practice?
Franklin, TN. South of Nashville.
Hi everyone,
I am a certified genetic counselor. Genetic counselors are masters degree trained health professionals with clinical training in medical genetics, counseling, and education. We must pass a national examination to practice, and adhere to a code of ethics. For those of you who have been frustrated by the lack of specialists who know something about MTHFR, I encourage you to seek out a genetic counselor by going to the http://www.nsgc.org and using the “Find a Counselor” search tool. If there is not a genetic counselor in your area, there are some who provide counseling over the telephone.
I’d also like to caution everyone to not to overestimate the importance of MTHFR In your health issues. The scientific research on this gene is still very early and mixed. Carriers of a single gene change are affected very differently than people who have two gene variants. Carriers of a single variant are very common in the general population. Most carriers don’t even know they have the variant because it never causes problems. Even among people with two variants, the effect of the gene is very dependent on diet and even other genes, some of which we don’t understand yet. I’m not saying to ignore MTHFR, I’m just cautioning against broad generalizations that may not apply to you as an individual. MTHFR has become popular among naturopaths as a catch-all explanation for patient’s myriad health problems. The truth is more complicated.
Finally, I also want to caution people against some of the testing companies that Katie mentioned. Many of them overemphasize the importance of certain genes as a clever marketing tool. In fact the FDA has recently asked some of those companies (including 23andme and some nutrigenomics companies) to cease offering certain tests because of false claims of efficacy. The most trustworthy genetic testing is always through a certified genetics professional, either a physician who specializes in genetics, or a genetic counselor.
Thank you, Suzanna. I needed to read this.
Hello,
As a physician guiding patients through testing results such as 23 and Me, I both agree with Suzanna and disagree. Those of us who address such genetics issues always say “don’t treat SNPs, treat patients”. So Suzanna is correct in advising against over relying on such results. On the other hand, standard genetics does not explain the emerging field of epigenetics. Epigenetics is not black and white, but a thousand shades of a gray mosaic. Though 23 and Me has been restricted from making the health claims it was doing (a move I agree with due to its overgeneralizations), much information can be gleaned from this testing that can benefit patients health, present and future (keep in mind, I use this as a tool like any other test…I order it on some patients, but not on others). Science is scratching the surface of the field of epigenetics and it is promising significant rewards. The hope for benefit is so great that 23 and Me has partnered with industry to search for links to diseases (and industry is paying a pretty penny for the data). MTHFR has been linked to cancers, birth defects, asthma, depression, anxiety, and many other diseases. How many more will be discovered? As Suzanna indicated, finding someone knowledgeable in this field is important, but if they tell you not to worry about your results, they look for someone else.
Blessings,
Eric Potter MD
fascination Amazing information! Thank you!??
You are welcome.
Hi Suzanna!
I have the c677t mutation. My holistic Dr. (Mary shrick in OK) has me on her supplements for it but my question is, if it’s difficult for those with this mutation to detox then what’s a good way to detox effectively?
The problem with this is that I almost died from extensive pulmonary embolisms in both lungs and DVT in various parts of my body. And my hematologist still just brushes this MTHFR mutation off, stating just what you said. I think there needs to be a happy middle here. If someone almost dies from this mutation (given there were no other factors when my symptoms first began) then it should be taken very seriously. I find that most doctors still just claim it is insignificant. My question is, why test at all then? Even in patients like me if doctors aren’t going to even offer suggestions about how to manage it? Needless to say, I can’t find another hematologist fast enough. The fact that my hematologist smiled at me when reading my results as if to say, “you’re all clear!” was frustrating. I am not “all clear.” I have clots in my lungs still and new DVT symptoms and every other mild-severe symptom of MTHFR aside from cancer. I even have symptoms of TIAs.
It seems that all the Paleo/holistic people I follow have started hitting on MTHFR a lot! I don’t know if it’s coincidence or if I’m just noticing it more because I’m personally doing more research and it’s popping out at me. Either way, thanks for this post! I recently found out that I’m homozygous for MTHFR….I also have a lot of SNP’s (both homo and hetero) for other things in the methylation and detoxification process, like COMT, CBS, MTR, and MTRR….as well as things like MAOA and DAOA. It’s extremely interesting but very confusing on where to start. I began supplementing with extra methylated folate and B12 last week but found that I became very anxious, withdrawn, and depressed. I’ve read that people who have COMT may have a hard time with methyl donors and need to get those issues straightened out first before tackling MTHFR. I’m also worried about my homocysteine levels, as I’m pretty sure that I don’t produce enough glutathione to detox properly because my body is high in aluminum and other heavy metals. My husband and I aren’t trying for children currently, but probably within the next couple years (we are avoiding naturally)….and I’m so afraid of miscarrying or having something go wrong because of my genetic mutations. My husband is heterozygous for MTHFR, so there is ZERO chance of our kids have 2 normal genes, and a 50% chance they would be homozygous. I also have lymphocytic colitis, psoriasis, and have been dealing with more aching joints in my hands. So I definitely have some autoimmune stuff going on as well.
Interesting….I never heard of this until my daughter was scheduled for surgery and I told him my grandma has Factor V Leiden so her doctor tested her to make sure she didn’t have it. She doesn’t, but she is heterozygous for MTHFR mutation. The doctor just told her no birth control pills ever in her life. I’m wondering if all this applies to her because she is just heterozygous for MTHFR mutation. Opinions?
Good morning Lisa,
You are asking if your daughter has to address all of these issues based on being heterozygous for MTHFR. Short answer…it depends. Awareness of this genetic predisposition is the first step. Second step, learning to avoid those things that might turn the predisposition into actual symptoms. Third step, learning to recognize when certain symptoms might be a sign that the predisposition is allowing illness to manifest. All together, learning to care for oneself.
Blessings,
Eric Potter MD
Thank you! She gets a lot of headaches so I’m going to research more.
I don’t know how old these comments are, but I would not be on birth control unless it was progesterone only or the copper IUD. I was just hospitalized with extensive (re: unable to count there were so many) clots in both of my lungs with symptoms of DVT in both legs, my left jugular, left brain, left arm, spine, and abdomen. This all happened 4 months after starting birth control again. Granted, I had symptoms of “mild” DVT for years, but the birth control seemed to push it over the edge into dangerous territory. I tested positive for heterozygous MTHFR this week and after researching, I realize I have every symptom associated with this mutation. Just please tell your daughter to be careful, and even the SLIGHTEST hint of DVT pain, go get checked. I brushed my “mild” symptoms off thinking there was no way I could have blood clots at such a young age, especially since I am fit and healthy and workout almost every day. But that doesn’t matter, unfortunately.
i work for a functional medicine doctor and work with patience will all sorts of issues that M.D.’s can’t/won’t/don’t know how to treat. MTHFR is an issue that can be worked with,simply most of the time. Find a good Naturopath or functional medicine doctor. M.D.’s don’t always look for the “whys” in the problems we have. Everything has a cause so therefore a solution or management. Don’t give up!
I agree with Erin. It was my Functional Medicine practitioner who found that my homocysteine was through the roof then tested me for the MTHFR mutation which I tested positive for. She recommended a supplement with folinic acid (not folic) or some other blends that are more bioavailable (my friend uses Life Extension brand). Just make sure you buy supplements from a reputable source that has been 3rd party tested. I’ve definitely found that the cleaner I eat (no soy, dairy, gluten, etc) the better I feel. Thanks, Katy.
Thank you for a great explanation of this complex problem. As I have cared for patients with MTHFr and its associated genes, this education is always key to empowering patients to care for their health. I will likely use your explanation if that is okay.
Blessings,
Eric Potter MD
Thank you for the informtion and links in this article. I would like to offer that MTHFR is one part of the methyl cycle. It is very important to find a practitioner who understands as much as possible about the entire cycle. My initial instructions from a practitioner regarding MTHFR overloaded my system with methylated B vitamins and it send me into toxic ammonia overload, and it took several months for me to recover my previous state of health.
Katie-You are awesome!
Katie, what type of methyl-B12 do you use to help your body utilize the L-MTHF? I have been diagnosed with homozygous A1298C MTHFR and have not been able to find relief from the problems that come with it. Absolutely wonderful post, thanks!
Hi Cara,
I’m homozygous 1298 as well. My naturopath put me on Douglas Labs Methyl Folate L-5-MTHF, 60 tabs per bottle. I also take methylated B12, from either Douglas or Thorne. While they are excellent supplements, I felt the biggest difference when I started taking 2000 IUs of vitamin D after my naturopath (gosh, she’s smart!) found me to be quite deficient.
Aside from a miscarriage at nine weeks, I have had great health but was very grateful to find out about the mutation. I took the methyl folate while pregnant with my son last year, and will have my daughter tested for MTHFR soon.
Genetically speaking, my mom had herself tested and is heterozygous for 1298. Unfortunately my father is out of the picture (divorced long ago) and so I’m not exactly able to hit him up for his side of the story!
Hoping my brother gets checked too.
I wish you all the best and hope your health improves! 🙂
Hi,
I am homozygous 1298 as well. I am currently breastfeeding and take thorne prenatal vitamins. Do you take a certain form of vitamin D? Also, do you have a preferred brand for vitamin D?
I was tested in the past and very D deficient. But I haven’t been taking any recently besides what’s included in the prenatal.
Rachel, when I was tested deficient in Vit D. I was at 22. So my doctor (who is an MD but she practices in Alternative and Holistic Medicine specializing in Women’s Health) put me on 10,000 IU of Vit D, until my numbers come up. After about six months or so, I retested and I brought it up to 60 (which is in the optimal range). So now I dropped my Vit. D supplement to 5,000 IU.
From what my doctor told me, 2000 IU is the level that children should be taking. Adults should be taking 2,000 to 5,000 if they are within range. And those that are deficient should be taking 10,000 a day!
I brought mine up by taking the NOW brand.
There is a great book on the subject of Vitamin D that I feel every person should read. It is called The Vitamin D Solution by Dr. Michael Holick. He also writes about the levels that I mentioned up above.
Excellent article! Can’t wait to get tested!??