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You’ve probably heard about the MTHFR gene. But do you understand what it is and how it relates to your health? And if you have an MTHFR genetic variation, what can – or should – you do about it? Ahead, a look at the MTHFR gene and how variations in the expression of the gene can affect your thyroid. We’ve included input from naturopathic physician Dr. Doni Wilson and geneticist and nutritionist Dr. Denise Furness, featured in our August 2022 virtual Speaker Series conversation about MTHFR.
First, let’s clarify some terminology. MTHFR is an abbreviation for methylenetetrahydrofolate reductase, and MTHFR refers to both the gene and the enzyme that the gene produces. It’s common to hear discussion of “MTHFR mutations,” but according to Dr. Furness, that term is misleading because while mutations cause diseases, variations do not. Says Furness, “I urge all of you to think about using terminology like ‘variation.’”
The MTHFR enzyme has an important role: it converts folate and folic acid, “methylating” it into methylfolate, making it more usable by the body. Folate is the natural form of vitamin B9, and folic acid is a synthetic form of this vitamin that is added to foods to fortify them. Both folate and folic acid need to be converted into methylfolate to function in the body. Methyfolate is required to balance our homocysteine levels and support all of the methylation reactions that occur in the body.
It all works well unless there is a variation in the MTHFR gene- a change within the gene’s DNA sequence. We inherit our MTHFR genetic profile from our parents, and every individual can have anywhere from zero to three MTHFR variations – known as SNPs (“snips”). The more SNPs we have, the more our potential ability to methylate is reduced. According to Dr. Furness, “if you don’t know much about methylation, it is needed for DNA synthesis and repair, for turning genes off and on, and to metabolize our hormones. It’s also important for detoxification of other chemicals and heavy metals.”
Another critical function of methylfolate is to help keep our homocysteine levels in check. Elevated homocysteine levels promote inflammation. Dr. Furness explains: “Homocysteine is an intermediate amino acid. When there’s a build-up of homocysteine, it can damage cells that line our blood vessels and increase our risk for cardiovascular disease, cognitive decline disorders like Alzheimer’s and dementia, as well as pregnancy complications.”
A genetic DNA test – usually performed by swabbing the cheek for saliva -- can detect MTHFR variations. Typically, tests look for two common MTHFR variations, known as 677 and 1298.
It’s estimated that 50 to 60 percent of the population has one or more MTHFR gene variations.
To affect your health, the genes with the MTHFR variations need to be “expressed.” Expression is the process whereby a gene gets “turned on” or activated in a cell.
According to the Merck Manual, various factors affect gene expression, including: “genetic makeup, exposure to harmful substances, other environmental influences, and age.”
When the genes are expressed, the MTHFR enzyme doesn’t work well, and not enough methylfolate can be produced. In fact, the ability to produce methylfolate can be reduced from 30 to as much as 70 percent in people with MTHFR variations.
The lack of methylfolate and the resulting impaired methylation has many health effects:
- High homocysteine, which can increase inflammation and increase the risk of cardiovascular disease and dementia
- Impaired synthesis of glutathione and brain neurotransmitters, which increase the risk of depression and other brain-based conditions
- An increased risk of blood clots, heart attack, stroke, cancer, birth defects, mental health conditions, and autoimmune conditions, including autoimmune thyroid diseases.
According to Dr. Doni Wilson, there aren’t any specific symptoms of having an MTHFR variation. But, says Dr. Wilson, “some of the most common symptoms of conditions caused by MTHFR would be fatigue, anxiety, and depression.”
There’s no evidence that MTHFR directly causes Hashimoto’s thyroiditis or autoimmune disease. But studies have found that Hashimoto’s patients are genetically more susceptible to MTHFR variations, and patients with hypothyroidism are more likely than the general population to have MTHFR variations. There doesn’t appear to be a link between the presence of MTHFR gene variations and the severity of autoimmune thyroid disease.
Indirectly, however, MTHFR genetic variations are an underlying factor that could be a root cause or a trigger. Dr. Furness explains:
“MTHFR can affect or influence our risk of autoimmune disease through many different indirect pathways. If methylation is not occurring as it should in the body, chemicals and toxins can build up. We can’t manage our stress hormones, which can trigger chronic inflammation in the body. All of these things can link to the development of an autoimmune disease. So, if you think about what causes an autoimmune disease, there’s the genetic component and environmental component and then something that triggers the immune system. If someone’s methylation pathways aren’t functioning properly, it’s going to affect the levels of toxins. We know that when it comes to autoimmune disease, people are often more sensitive to chemicals and toxins; these are triggering that immune system, that chronic inflammation in the body. It’s not the genes in isolation. It’s the genes with that person’s lifestyle symptoms, triggers.”
Elevated homocysteine levels — which result from MTHFR variations—are a risk factor for developing a thyroid disorder. Research has shown that people with hypothyroidism have higher levels of homocysteine, on average, compared to people with normal thyroid function. Elevated homocysteine can also affect thyroid function and increase the risk of cardiovascular disease in people with hypothyroidism.
Specifically, research has also shown that MTHFR variation-related nutritional deficiencies – especially in B vitamins – may increase the risk of developing a thyroid condition. Interestingly, around 40% of people with hypothyroidism have some Vitamin B12 deficiency.
If you’re one of the estimated 60 percent of people with MTHFR variations, you may have an impaired ability to methylate and problems with your methylation pathways. And if you have Hashimoto’s thyroiditis or hypothyroidism, the chance that you not only have MTHFR variations but are actively expressed is higher. But should you get tested to find out?
Dr. Wilson recommends that you start by addressing your hypothyroidism and get on the right dose of thyroid hormone replacement to stabilize thyroid levels. After that, she recommends focusing on the controllable factors that affect our health. Says Dr. Wilson:
“Genetics are about 20 percent of what’s going on with your health. The rest of what’s influencing your health is based on your environment, lifestyle, and stress exposure. It’s our exposures in the world that have more to do with your tendency toward autoimmunity and low thyroid function. And, of course, stress affects adrenal function, which affects cortisol and adrenaline production. And so to me, we want to address those things first.”
Dr. Wilson recommends addressing all these factors before testing because, if tests show MTHFR variations, “I’m going to guide patients right back to these stress and lifestyle issues, address diet and inflammation, minimize toxin exposure, and support B vitamin levels.”
We asked Dr. Furness when you should be concerned about having MTHFR variations. She has a different way of looking at the issue. Says Dr. Furness:
“I think we need to turn that around and say, it’s not actually about being concerned. It’s about being educated, knowledgeable, and empowered because we all have these genetic strengths and weaknesses. Remember, this is not clinical genetics, we’re not diagnosing a disease by finding an enzyme that doesn’t work as efficiently as quickly, and we can do something about it. Rather than be concerned about having an MTHFR variation, I recommend you take it as ‘I’ve now identified an area that I can work on to improve my health.’”
According to Dr. Wilson, the next step after discovering MTHFR gene variations is to double-check your multivitamins, prenatal vitamins, and B complex supplements. If the labels say “folic acid,” don’t continue to take those products. Instead, switch them for products with methylfolate (also listed as 5-MTHFR or 5-methyl tetrahydrofolate.)
Says Dr. Wilson: “Next, measure your homocysteine levels. This is a blood test that can be done from a standard lab and should be covered by insurance. Your homocysteine should be at about 7. If it’s higher than 7, I would work with a practitioner to help you finetune it because it’s very tricky to do on your own. This is especially important if your homocysteine is higher than 10 or lower than 4. Then we can see if we need to add more methylfolate or methyl B-12.”
In addition to supplementing with methylated forms of folate and Vitamin B-12, which have been proven to help lower homocysteine levels, other recommendations for those with MTHFR variations include an anti-inflammatory diet, glutathione supplementation, and active stress reduction.
Both Drs. Furness and Wilson emphasized that having MTHFR variations is not the fundamental problem. The real issue is your environment, and, says Dr. Furness, “you can change your environment!
One factor that’s in your control is getting quality care for hypothyroidism. It’s simple to get your thyroid levels tested with the Paloma Complete Thyroid Blood Test kit. The affordable and convenient at-home thyroid test kit from Paloma comes with everything you need to test Thyroid Stimulating Hormone (TSH), Free Thyroxine (Free T4), Free Triiodothyronine (Free T3), and Thyroid Peroxidase Antibodies (TPO), with an option to add on tests for Reverse T3 (RT3) and vitamin D.
Consider connecting with Paloma’s top thyroid doctors, who provide comprehensive diagnosis and optimal treatment of hypothyroidism from the convenience of your home. Paloma’s thyroid-savvy health care providers across the nation have successfully worked with many thyroid patients to optimize their thyroid function.
Finally, if you need help ensuring that you’re eating a diet rich in V vitamins and glutathione, Paloma Health’s thyroid nutritionists offer virtual consultations to help you craft a plan to reduce homocysteine levels and support your health with food and nutrition.