You may have heard of the term “MTHFR gene mutation” and be wondering what it is. First, I’d like to say that I prefer the term MTHFR gene variation rather than mutation. The word variation is more empowering, and in my opinion, also more accurate.
While the word mutation implies an occurrence that is rare, unnatural or flawed, the MTHFR gene variation is common. In fact, it’s present in up to 55 percent of the European population, is naturally occurring, and often has no negative health consequences – unless expressed.
I chose to use this terminology after learning that I was a carrier of two copies of the MTHFR gene. When I first saw my test results, I thought to myself, I have bad genes. I am flawed. I am broken. I am bad. It’s quite easy to go down that path and feel victimized, and I don’t ever want you to feel victimized by knowing something about yourself.
The reason we do tests and learn about our genes is to feel empowered. While we can’t change our genes, I can tell you that we can absolutely change their expression! So if you have the MTHFR gene variation, or are thinking of testing for it, I hope that this overview empowers you.
In the following article, you’ll discover:
- Symptoms and diseases related to the MTHFR gene variation
- Genetic effects on nutrient extraction and common nutrient deficiencies
- How to test for the MTHFR gene variation and check your homocysteine levels
- How to support your methylation pathways with food and supplements
Understanding the MTHFR Gene Variation
It’s important to understand what it means to have the MTHFR gene variation in order to determine if it may be contributing to some of the symptoms you’ve been experiencing.
The gene involved is the MTHFR (Methylenetetrahydrofolate Reductase) gene. This gene codes for the MTHFR enzyme, the enzyme that converts the amino acid homocysteine to methionine, a building block for proteins.
As a result, individuals with a genetic variation and low activity of the MTHFR enzyme may present with elevated homocysteine levels, which have been associated with inflammation, heart disease, pregnancy complications, and even miscarriages. It has also been associated with higher rates of Down syndrome and birth defects in offspring, as well as other issues later such as depression, an increased risk of blood clots, and a higher risk of certain cancers. Some of my clients with Hashimoto’s and the MTHFR gene variation have even reported having bigger blood clots during their menstrual cycles.
One of the key things to note is that this gene variation also prevents people from properly methylating, which is one of the body’s key detox processes that helps them get rid of toxins. Methylation impairment can result in an impaired ability to clear out certain toxins such as mercury and arsenic, and may lead to estrogen dominance. Symptoms like brain fog, multiple chemical sensitivities, depression, irritability and anxiety are related to impaired methylation. As these symptoms are all too common in Hashimoto’s, I designed the Liver Support Protocol (from my book Hashimoto’s Protocol) to support the methylation pathways.
Studies have shown that another possible consequence of this gene variation includes being sensitive to certain anesthetics, such as nitrous oxide, which is commonly used for dental surgeries. If you’re due for an operation and have the MTHFR gene variation, you can click on and print the following articles for your surgeon and anesthesiologist to share this information with them and seek alternative anesthetic options:
It’s not all doom and gloom, however – Dr. Ben Lynch (author of the book Dirty Genes) reports that those who are born with the MTHFR gene variation may also have some advantages, such as being more alert, productive, and focused. As the owner of two MTHFR gene variations, I can surely attest to this!
Genetic Effects on Nutrient Extraction
The genetic variation can also play a role in vitamin deficiencies. Specifically, elevated homocysteine levels often caused by the MTHFR gene variation have been associated with nutrient deficiencies in vitamin B9 (folate), B6, and B12.
It may seem like common sense to take a supplement to address a deficiency in folate, but not all sources of vitamin B9 are created equally. While vitamin B9 can be found naturally in foods in the form of folate, it can also be found in the form of folic acid, a manufactured version of folate that is present in most bargain priced multivitamins and often added to processed foods.
Unfortunately, folic acid can be highly problematic for individuals with the MTHFR gene variation, as they may have a difficult time processing this form of folate. Some professionals claim that this type of synthetic folate 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. (By the way, if you’re looking for a better multivitamin, I recommend Nutrient 950 by Pure Encapsulations, which contains the active version of folate.)
Correlation Between the Genetic Variation and Hashimoto’s
You may be wondering, “Does everyone with Hashimoto’s have this variation, and does it make Hashimoto’s worse?”
The answer, thankfully, is no! In fact, a recent study by Arakawa and colleagues of thyroid patients with Hashimoto’s and Graves’ found that polymorphisms – that is, gene variations that may lead to the abnormal expressions – were as common in autoimmune thyroid disease as they were in the normal population. Additionally, the authors concluded that the severity of autoimmune thyroid disease (AITD) did not correlate with whether one had this gene variation or not.
Here’s an excerpt from the study:
Genotype and allele frequencies of the MTHFR +677C/T and +1298A/C polymorphisms showed no significant differences between healthy controls and patients with AITD; these genotype and allele frequencies did not influence the prognosis of AITD.
In other words, the likelihood of having one or both of the MTHFR polymorphisms, as well as the frequency of variants (alleles) of the MTHFR gene, were not found to be more prevalent in those with autoimmune thyroid disease compared to those who do not.
Nonetheless, the MTHFR gene variation does appear more commonly in those with hypothyroidism.
Testing for the MTHFR Gene and High Homocysteine Levels
You can take genetic tests to find out whether you have this gene, as well as high homocysteine levels.
It’s important to test for both homocysteine levels and the MTHFR gene variation because, while you may not have the gene that affects the methylation pathways, you may still have elevated homocysteine levels, which tell us the level of inflammation in our bodies. Elevated homocysteine levels may also indicate a deficiency in B vitamins.
Testing for homocysteine levels is now available through many labs and can be assessed with a blood test.
Please note, the optimal reference ranges for homocysteine are somewhat of an emerging science. While higher levels of homocysteine have been associated with numerous health complications, levels of homocysteine that are too low can also be problematic and have been associated with peripheral neuropathy (often felt as hand and arm tingling), and an impaired ability to make glutathione, an important antioxidant that reduces inflammation in the body. Low levels of glutathione have been correlated with Hashimoto’s and heavy metal toxicity.
Depending on the lab, some reference ranges may define homocysteine excess as >10 or 11 µmol/L, while levels under 6 µmol/L may be considered too low.
Other reference ranges, such as the one reported by Medscape, break down homocysteine levels by age and gender. (Levels of homocysteine generally increase with age.)
- Age 0-30 years: 4.6-8.1 µmol/L
- Age 30-59 years: 6.3-11.2 µmol/L (males); 4-5-7.9 µmol/L (females)
- Age >59 years: 5.8-11.9 µmol/L
According to functional ranges, however, the optimal homocysteine levels range seems to be somewhere between 5-7 µmol/L. I imagine that, as with most labs, homocysteine levels are simply numbers to consider when looking at the big picture of overall health, and individual variations need to be considered.
As for testing for the MTHFR genetic variation, many labs also offer tests for this gene. For example, you can order a saliva test kit from 23andme.com, and many individuals can get the tests from their physicians covered by insurance. You can upload your results to geneticgenie.org, which will then tell you if you have the genetic variation.
However, some may be concerned with this genetic information getting reported on insurance or to employers. There have been concerns that having a MTHFR variation or elevated homocysteine levels could potentially interfere with future insurance coverage that may limit pre-existing conditions.
There are two possible MTHFR variations that you may have. Both the 677 gene and the 1298 gene can carry the MTHFR variations.
These are the different types of potential variations to look for:
- Homozygous variation – You can have two copies of the same MTHFR variation.
- Heterozygous variation – You can have one copy of the MTHFR variation.
- Compound heterozygous variation – You can have one variation on both the 677 and 1298 genes.
Elevated homocysteine, whether you have or don’t have the MTHFR gene variation, can indicate inflammation in the body. While people with elevated homocysteine may benefit from diet and supplementation (especially if the elevation was caused by inflammatory foods and nutrient deficiencies), other reasons for inflammation should be investigated with your practitioner as well.
Food as Medicine
If you do have this gene variation, remember: genes are NOT your destiny! In fact, I personally have two copies of the MTHFR gene variation, but I’m alive and well. In other words, the presence of a gene does not always imply gene expression. It all depends on your unique genetic makeup, lifestyle choices, and interventions. There are many things you can do to support and optimize your methylation pathways.
First, I recommend eating a diet that will lower the overall inflammation in your body, such as the Root Cause Paleo diet. (The plan I recommend doesn’t just eliminate processed foods, but it also focuses on a high intake of veggies).
As for addressing high homocysteine levels, there are two main nutrient pathways of breaking down homocysteine. Nutrient deficiencies along either of the pathways may result in elevated homocysteine levels.
One of the pathways involves the use of the B vitamins, while the other one uses trimethylglycine (Betaine) to help with metabolizing homocysteine. The following nutrients may support methylation and homocysteine levels:
Folate (B9) – You can find folate present in its activated form in real foods such as green leafy vegetables (spinach, collard greens, and romaine are some examples), asparagus, papaya, beans (especially lentils), avocados, brussels sprouts, nuts, seeds, and beets.
Vitamin B6 – Rich sources include meats, beans, avocados, and nuts and seeds.
Vitamin B12 – This is primarily found in meats, and may be deficient in a vegan and vegetarian diet.
Riboflavin (B2) – Rich sources include lamb, eggs, liver, salmon, and mushrooms.
Betaine AKA trimethylglycine – Betaine can be found in beets, whole grains like quinoa (which some individuals may not be able to eat), and spinach.
Supplements to Support Methylation
Of course, we may not be able to get enough of the needed nutrients from food alone. Individuals with the MTHFR gene variation and high homocysteine levels may also benefit from activated versions of folate, B6, and B12, such as methylated folate (also known as L-5-MTHF Folate, methylfolate, 5-formyltetrahydrofolate or NatureFolate), Pyridoxyl-5-Phosphate (P5P), and methylcobalamin, respectively.
In my survey of 2232 patients with Hashimoto’s, 45 percent of participants said they felt better after adding methylation supporting supplements like methylated folate, B12 and B6 to their regimen.
Another 59 percent reported feeling better with adding the digestive enzyme betaine with pepsin as well, and I suspect this may in part be due to improved methylation. The top symptoms that improved included energy, pain, and mood.
Thus, if you also happen to have low stomach acid (as many people with Hashimoto’s do), taking the protein digestive enzyme Betaine with Pepsin from Rootcology is another great way to get extra trimethylglycine. Betaine HCl and pepsin are necessary for adequate absorption of Vitamin B12, as well as protein, calcium, and iron. I developed the Rootcology MTHFR Pathways supplement to contain synergistic nutrients that support homocysteine pathways, including activated forms of folate, B2, B6, and B12, and trimethylglycine (Betaine).
Please note: Rootcology currently ships to the United States only.
This combination may help to facilitate the efficient metabolism of homocysteine and maintain a healthy homocysteine pathway, allowing for the normal production of its necessary and important end products, including the sulfur-containing amino acids taurine and cysteine, and the neurotransmitters norepinephrine and dopamine.
An optimally functioning homocysteine pathway provides methyl and sulfur groups for biochemical reactions such as detoxification, healthy immune function, ideal joint and cartilage structure, and brain and cardiovascular health – so it’s important to metabolize homocysteine effectively.
In addition, many of the lifestyle interventions helpful for Hashimoto’s are also beneficial for the MTHFR variation. I discuss these interventions in more detail in my first book, Hashimoto’s: The Root Cause, as well as in my second book, Hashimoto’s Protocol.
What if you feel worse after taking MTHFR Pathways or Betaine?
First and foremost, you’re not crazy, and you’re not alone. While most people with Hashimoto’s tend to feel better, about 8 percent of people will feel worse with MTHFR Pathways. Some of the people who feel slightly worse (i.e. who may experience more anxiety and irritability) may benefit from a dosage reduction, in the case that their pathways are moving too quickly. However, if “feeling worse” lasts more than a few days, this could be due to overmethylation, other gene variations, or a sensitivity to the supplements, and the supplements should be discontinued. As always, listen to your body and to your knowledgeable practitioners.
Other Nutrients That Can Help Symptoms
Curious about other nutrient deficiencies that may be the root cause of your symptoms, and supplements that may help address them? Download my free Supplements to Subdue Symptoms eBook to discover which supplements benefit which symptoms and more!
Some people have a genetic variation that may impair their detox abilities, affect how they absorb certain B vitamins, and contribute to their symptoms. Nonetheless, knowledge leads to empowerment. Again, while we can’t change our genes, we can absolutely change their expression!
You can support your methylation pathways with dietary interventions and supplements. To kickstart your path to wellness, I recommend testing your homocysteine levels and checking to see if you have markers for the MTHFR gene variation. If you do, supporting your methylation pathways with supplements may help reduce some of the symptoms you’re experiencing.
I’ve created a helpful graphic to help you remember how to support your methylation pathways:
And of course, I’d like to reiterate this:
Share it on Facebook to remind yourself daily that knowledge about our bodies and our health EMPOWERS us and gets us one step closer to feeling our BEST!
I hope that this information empowers you and I wish you all the best on your healing journey!
P.S. When you sign up for my newsletter, you can also download a free Thyroid Diet Guide, 10 Thyroid friendly recipes, and the Nutrient Depletions and Digestion chapter for free. You will also receive occasional updates about new research, resources, giveaways and helpful information.
For future updates, make sure to follow me on Facebook!
- Dell’edera D, Tinelli A, Milazzo G, et al. Effect of multivitamins on plasma homocysteine in patients with the 5,10 methylenetetrahydrofolate reductase C677T homozygous state. Molecular Medicine Reports. 2013;8(2): 609-612. doi:10.3892/mmr.2013.1563.
- McNulty H, Pentieva K, Hoey L, Strain J, Ward M. Nutrition throughout life: folate. International journal for vitamin and nutrition research. 2012;82(5):348-354. doi: 10.1024/0300-9831/a000130.
- Zappacosta B, Mastroiacovo P, Persichilli S, et. al. Homocysteine lowering by folate-rich diet or pharmacological supplementations in subjects with moderate hyperhomocysteinemia. Nutrients. 2013;5(5):1531-1543. doi:10.3390/nu5051531.
- Prinz-Langenohl R, Brämswig S, Tobolski O, et al. [6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wildtype 677C→T polymorphism of methylenetetrahydrofolate reductase. British Journal of Pharmacology. 2009;158(8):2014–2021. doi: 10.1111/j.1476-5381.2009.00492.x.
- Dietary Supplement Fact Sheet: Folate. National Institutes of Health. http://ods.od.nih.gov/factsheets/Folate-HealthProfessional/. Updated April 20, 2016. Accessed January 2, 2018.
- Dietary Supplement Fact Sheet: Vitamin B6. National Institutes of Health. http://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/. Updated February 11, 2016. Accessed January 2, 2018.
- Online Lab Testing & Blood Tests for Functional Medicine. My Labs for Life. www.mylabsforlife.com. Accessed June 3, 2013.
- ZRT Laboratory – Innovative lab testing made simple. ZRT Laboratory. www.zrtlabs.com. Accessed June 3, 2013.
- Walsh N. Folic acid cancer debate continues. MedPage Today. 2013. http://www.medpagetoday.com/HematologyOncology/ColonCancer/37008. Accessed June 3, 2013.
- Lynch B. What is MTHR?. MTHFR.net. http://mthfr.net. Accessed June 3, 2013.
- Arakawa Y, Watanabe M, Inoue N, et al. Association of polymorphisms in DNMT1, DNMT3A, DNMT3B, MTHFR and MTRR genes with global DNA methylation levels and prognosis of autoimmune thyroid disease. Clinical and Experimental Immunology. 2012;170(2):194–201. doi:10.1111/j.1365-2249.2012.04646.
- Nagele P, Zeugswetter B, Wiener C, et al. Influence of Methylenetetrahydrofolate Reductase Gene Polymorphisms on Homocysteine Concentrations after Nitrous Oxide Anesthesia. Anesthesiology. 2008;109:36-43. doi:10.1097/ALN.0b013e318178820
- Pollak A, Mueller-Malesinska M, Lechowicz U, et al. MTHFR 677T is a strong determinant of the degree of hearing loss among Polish males with postlingual sensorineural hearing impairment. DNA Cell Biol. 2012;31(7):1267-1273. doi: 10.1089/dna.2012.1607.
- Lynch B. Dirty Genes: A Breakthrough Program to Treat the Root Cause of Illness and Optimize Your Health. New York, Harper One: 2018.
- Elhomsy G. Homocysteine: Reference Ranges. Medscape. https://emedicine.medscape.com/article/2085682-overview. Published January 18, 2013. Updated November 21, 2014. Accessed January 31, 2018.
- Pizzorno J. Homocysteine: Friend or Foe? Integrative Medicine: A Clinician’s Journal. 2014;13(4):8-14.
Note: Originally published in May 2015, this article has been revised and updated for accuracy and thoroughness.