The link between MTHFR and Thyroid health
MTHFR is a gene that has been known for several decades now, but the implications that this gene can have on our health are only becoming well known recently.
If you’ve tested positive for the MTHFR gene, you’re probably still learning about all the impacts it can have on your health. If you haven’t been tested for it, but have some concerns about your health, then I definitely recommend learning more about it and consider getting yourself and your loved ones tested.
MTHFR is just one type of gene that we can have issues with and certainly it’s not the be all and end all of our health (nothing is) but it is showing to be a very important one with some wide ranging health implications such as mental health, heart disease, digestive health, fertility issues and more. MTHFR is also linked to the health of our thyroid, and the health of our thyroid has an impact on the activity of our MTHFR gene.
I know I tend to get a little carried away when writing these articles, so for those of you have are in a hurry, I introduce my new addition to my articles, a TLDR summary (TLDR = too long; didn’t read).
- The MTHFR gene produces an enzyme which is responsible for the conversion of methylfolate, the activated form of folate, folinic acid and the synthetic, not good for us form, folic acid.
- A fairly large proportion of the population has some form of mutation in this gene which causes underactivity of certain chemical pathways in the body (known as methylation) à which causes methylfolate deficiency à which causes lots of health problems because it’s a very important nutrient in our biochemistry.
- Our thyroid status affects the expression of the MTHFR gene, regardless of whether you have the polymorphism (gene mutation) or not.
- MTHFR polymorphism can reduce detoxification of chemicals and also affects immune health, which can contribute to the presence of autoimmune thyroid disorders such as Graves and Hashimotos disease.
- If you don’t have methylation working properly, you’re not turning your genes on and off properly, and this can be linked to cancer, in particular thyroid cancer. There is an increased risk of thyroid cancer in those who with homozygous C677T MTHFR.
Still reading? Cool!
Here’s a bit of a summary about what MTHFR is and its impact on your health.
The MTHFR gene produces an enzyme in the body called methylenetetrahydrofolate reductase which is responsible for converting folate, folic acid or folinic acid into a form that the body can use – methyltetrahydrofolate, or commonly shortened as methylfolate.
Some people have a genetic mutation in the MTHFR gene which affects this pathway, and as a result causes a lot of other issues in our health. This methylation pathway is central to our biochemistry, so defects in this gene cause wide ranging implications and are associated with a huge amount of conditions, including but definitely not limited to:
Neural Tube Defects
Chronic Fatigue Syndrome
There are two main MTHFR genes we are currently aware of (there are some other types but these are rarely tested or implicated in conditions), and your combination of these genes, as well as you diet and lifestyle, affects how much of an impact this gene has on your health. If you have the MTHFR gene mutation and you are consuming synthetic folic acid such as from fortified foods and certain supplements(*cough*most supplements out there), this can worsen your health as well, by blocking up the methylation pathways and your blood can accumulate with unmetabolised folic acid (UMFA). Accumulation of UMFA has been linked with inhibition of part of your immune system, particularly suppression of your natural killer cells (1).
|Heterozygous = 1 copy of the gene from either parent
Homozygous = 1 copy of the gene from each parent (most commonly)MTHFR C677T Heterozygous = 40% loss of function, present in approximately 45% of the population
MTHFR C677T Homozygous = 70% loss of function, present in approximately 20% of the population
MTHFR A1298C Heterozygous = No loss of function (debatable)
MTHFR C677T & MTHFR A1298C Compound heterozygous = 50% loss of function
MTHFR and Thyroid Health
If you have hypothyroidism, it’s likely your MTHFR gene is sluggish
And this can be whether you have the polymorphism or not.
If your thyroid is underactive then you have lower levels of a thyroid hormone thyroxine (T4) in the body. Our body converts T4 to T3, and those who have an underactive thyroid are mostly prescribed T3 medication, bypassing the T4 deficiency.
Giving T3 in isolation may address the thyroid function, but T4 is involved in the process of making vitamin B2 into its active form, flavin adeninde dinucleotide (FAD) (2). If you don’t have enough T4, you can’t covert Vitamin B2 to FAD properly, and your supply will be reduced.
If you don’t have enough FAD, your MTHFR enzyme slows down, causing low methyfolate levels, and subsequently can mimic the issues caused by having the MTHFR polymorphism (3).
“But my thyroid is normal.”
It’s important to be aware that the standard test for thyroid health is TSH, and if this is within normal range most people are brushed off, being told that their thyroid is ‘fine’.
I believe that solely testing TSH levels gives an incomplete understanding of thyroid function. The current ‘normal’ range of TSH 0.5-5.0 debatable, and in addition to this, other factors such as the presence of reverse T3 (which competes with natural free form T3) and the ratio of T4:T3 (which I recommend to be 3.3:1) is rarely considered.
It’s not uncommon that even if T3 and T4 are added to a test request that they will not be performed is TSH is within normal range. This is due to the restrictions placed on doctors and labs regarding what can be covered by Medicare. If you suspect that you have an underactive thyroid and your TSH is greater than 2, it may be worthwhile discussing whether you would benefit from seeking deeper investigations with your health practitioner, and it is likely that further testing will have to be paid for yourself.
MTHFR impact on thyroid
Conversely, if you have the MTHFR polymorphism then it can impact thyroid health. MTHFR polymorphisms can cause issues with detoxification of chemicals and immune health, factors which can contribute to the development of autoimmune conditions such as Grave’s disease and Hashimotos. Chemicals such as organophosphates and those in the halide group (fluoride, chlorine and bromide) can interfere with iodine levels, an essential mineral for thyroid health. We are exposed to these chemicals on a regular basis, and unless we are making steps to minimise our exposure they can often be in harmful amounts. People with MTHFR polymorphisms have a much harder time detoxifying these chemicals, and so their effect on the thyroid function is greater.
As impaired methylation causes lower levels of methyfolate, which is involved in the production of biopterin (BH4) (1) (4). This is needed to convert tyrosine into its active form and tyrosine is needed for formation of the thyroid hormones.
Some research has found that the MTHFR genotype C677T (homozygous) can increase the risk of developing thyroid cancer in caucasians (5) (6) (7). This is a pretty scary thing to hear, but rather than view it in a negative light we should embrace this knowledge and make the steps to reduce our risk factors. Also remember that the genes don’t cause problems in themselves, rather it is our diet and lifestyle that influences the expression of these genes – we have a lot of power over our health.
It is a good idea to make steps to avoid the harmful halide chemicals and other toxins, and ensure we are getting adequate nutrients necessary for our thyroid health (you can read more about this here). Ensure you’re getting the right nutrients for methylation through your diet, and definitely avoid synthetic folic acid. If you are homozygous for C677T it may be a good idea to get baseline thyroid ultrasound, and repeat this every year or so.
If you would like to learn more you can watch a presentation by Dr Ben Lynch here.
1. Lynch B. [Video Presentation].; 2013 [cited 2014 November 23. Available from: http://mthfr.net/mthfr-and-thyroid-disorders/2013/07/18/.
2. Cimino JA, Jhangiani S, Schwartz E, Cooperman JM. Riboflavin metabolism in the hypothyroid human adult. Proceedings of the Society for Experimental Biology and Medicine. 1987 Feb; 184(2).
3. Hustad S, Nedrebø BG, Ueland PM, Schneede J, Vollset SE, Ulvik A, et al. Phenotypic expression of the methylenetetrahydrofolate reductase 677C–>T polymorphism and flavin cofactor availability in thyroid dysfunction. The American Journal of Clinical Nutrition. 2004 October; 80(4).
4. Miller AL. The methylation, neurotransmitter, and antioxidant connections between folate and depression. Alternative Medicine Review: a journal of clinical therapeutic. 2008 Sep; 13(3).
5. Yang YM, Zhang TT, Yuan L, Ren Y. The association between the C677T polymorphism in MTHFR gene and the risk of thyroid cancer: a meta-analysis. European review for medical and pharmacological sciences. 2014; 18(5).
6. Chen Y, Wang B, Yan S, Wang YG. Significant association between MTHFR C677T polymorphism and thyroid cancer risk: evidence from a meta-analysis. Genetic testing and molecular biomarkers. 2014 Oct; 18(10).
7. Ozdemir S, Silan F, Uludag A, Atik S, Erscelcan T, Ozdemir O. Increased T-allele frequency of 677 C>T polymorphism in the methylenetetrahydrofolate reductase gene in differentiated thyroid carcinoma. Genetic testing and molecular biomarkers. 2012 July; 16(7).