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.
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.
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.
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.
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 Primal Multi by Designs for Health, which contains the active version of folate.). 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.
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.
Fortunately, one can order confidential tests that will not be reported to insurance by using online lab testing services, like Ulta Labs for Homocysteine or Ulta Labs MTHFR gene variation test.
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 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 the survey of 2232 patients with chronic disease, 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, taking the protein digestive enzyme Betaine with Pepsin 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. Designs for Health developed the Homocysteine Supreme supplement to contain synergistic nutrients that support homocysteine pathways, including activated forms of folate, B2, B6, and B12, and trimethylglycine (Betaine).
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.
I recommend supplementing as follows, based on your homocysteine level test results:
Homocysteine Test Results                Number of Capsules per Day
<6 µmol/L                                                       1
6-9 µmol/L                                                      2
9-15 µmol/L                                                    3
>15 µmol/L                                                     5
What if you feel worse after taking MTHFR Support Supplements or Betaine?
First and foremost, you’re not crazy, and you’re not alone. While most people with chronic disease 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.
The Takeaway
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 kick-start 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.