We’re all getting older, there’s no denying it.

And personally, I don’t think we should try to deny the aging process. But with aging comes the decline of health, and the increased risk for certain conditions. Choosing to take steps to slow down aging is not always about vanity – it can also be about improving your quality of life. The faster you age, the more your health will deteriorate, with conditions such as type 2 diabetes, arthritis, cancer, osteoporosis, Alzheimer’s disease and heart disease becoming more likely.

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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).

TLDR:

• 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:

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).

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.

Works Cited

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).
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It’s no new news that you should eat well while you’re pregnant. But what a lot of people don’t realize is the importance of eating well BEFORE you fall pregnant – during the preconception period. I try to teach my patients the importance of a healthy preconception care diet for both mother and father for at least 4 months before they are going to try to conceive.

Considering how hard it is to eat a healthy, nutrient dense diet when you have morning sickness, it makes the 4 month preconception care period all the more important (although I don’t think there’s a period of life when you shouldn’t eat well).

The reason for this time frame is because sperm can take 116 days to generate and during this time they are easily susceptible to damage. Similarly, the egg is vulnerable during maturation for around 100 days leading up to ovulation.

The damage that I’m referring to is of the genes of the sperm and the egg. If the genes of either are altered, then the foetus is more likely to develop a stronger tendency to genetic conditions such as autism, schizophrenia, genetic cancers, physical malformations and can increase general ill-health.

The thing about DNA is that some genes can be turned on and off like a light switch. Our environment i.e. the food that we eat and the chemicals that we’re exposed to control these switches – this concept is referred to as epigenetics. Methylation is another player in this whole process – it is a chemical ‘tagging’ process which aids in activating certain proteins in our body and silencing some genes.  This process is dependent on healthy levels of certain B vitamins – deficiencies in these vitamins can lead to an increase in DNA damage and when methylation isn’t working properly it can also cause problems in adults as well, such as heart disease, mood disorders and more.

Epigenetics research

While the research in this field is still in its infancy (haha, get it?) the research that we do have available is certainly interesting.

Most of the research that has been done in this field has been on mice. Any information that we get from animal research can never be fully extrapolated into recommendations for humans because mice and human metabolisms are worlds apart. It is a starting point however.

The human research that has been done has mostly been on the mother, and until recently it has mostly been during pregnancy. I believe the diet and supplements for the preconception period are just as important for the father however, and while there is some research in this area it is minimal in comparison.

The most well known study is that of the agouti mice. A selection of mice that were genetically identical were exposed to certain chemicals or dietary changes during their pregnancies that triggered gene changes in their pups, which was displayed as the production of the agouti protein, which turned their hair yellow. This same protein also prevented the mice from being able to feel full, and they developed obesity and were more prone to cancer and diabetes.  Some of the mice did not express this gene and so remained of normal weight and brown and some mice developed a mottled yellow-brown colour, only having partial gene expression. They were all genetically identical, however their gene expression was different.

Figure 1 The Yellow Agouti Mouse Model

Diet during pregnancy

Another study found that mice fed a high fat diet during pregnancy produced mice with altered metabolisms and also had brain changes which resulted in an impaired ability to feel when they were full. The third trimester and breastfeeding period were most important in this aspect.   Something to note is that the ‘high fat’ diet that these mice are fed is actually a concoction of hydrogenated vegetable fats, mixed with sugar. This is a far cry from what is commonly understood to be ‘fats’, as the production of these fats turns them into rather toxic substances. Your everyday, whole-food sort of fat found in avocadoes, nuts and seeds, fish and meat are not going to cause the same issue but hydrogenated fat found in fast food and processed food are going to cause problems.

A human study compared the amount of weight a mother gained in each of her pregnancies, and found that if the mother gained too much weight during a pregnancy the child was more likely to develop obesity, even more than 10 years later, compared to when the mother kept to a healthy weight range during her pregnancy. There are a lot of factors which could influence this, but a possible mechanism is that methylation can be reduced in those who are overweight.

This study looked at a group of women in Gambia and analyzed their diet and nutrient status during the preconception period. There were two groups of women analyzed – one who had conceived at the peak of the rainy season, and one who had conceived at the peak of the dry season. The women who had conceived at the peak of the rainy season had greater nutrient levels, notably the B vitamins essential for healthy methylation, and their babies were found to have greater amounts of DNA methylation. The study also found a correlation between the mothers BMI and methylation levels.

This study doesn’t mean that we have to wait until it rains to try to conceive, but rather it highlights the importance of eating nutrient dense food.

The moral of the story? If you’re planning to conceive, are pregnant or breastfeeding aim to eat a variety of fresh, whole, seasonal , nutrient dense foods and avoid exposure to environmental chemicals as much as possible.

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