While popular DNA tests may unlock your ancestry and tell you what percent Neanderthal genes are present in your DNA (Whoop dee doo), many of us in the quantified self, direct access healthcare community are looking for cost effective, actionable, real world applications of identifiable genetic mutations which may be linked to preventable and treatable medical conditions. The good news is that there are several easily identifiable genes associated with a growing number of potentially preventable and treatable medical conditions. In fact, mutations in one gene in particular, the mother freaking gene (MTHFR) as I call it, has been linked to blood clotting disorders, neural tube defects (such as spina bifida), Alzheimer 's disease, colon cancer, leukemia, schizophrenia, depression and an increased risk of miscarriages.
Did you know that for less than $150 you can learn:
why your antidepressants may not be working,
if you are at increased risk of miscarriages
if you are at a higher risk for heart attacks and strokes and,
identify potential complications you might experience from standard cancer treatments
This is all possible from the privacy of your own home… and in most cases without a doctor’s order!
Your 23andMe results may not tell you what you need to know
But don’t run out and just get any ole DNA test you can find on the internet. Popular DNA test kits, such as 23and, may not tell you what you need to know specifically about the MTHFR gene. However, with a free but little known service you’ll be able to unlock the clinical secrets hidden in your DNA test results.
I’ll show how to get this free clinical add on later, but first let’s answer the question, what is the mother freaking gene and what does it do?
In this article we explore one of the real world applications of DNA testing that may answer the question as to why your antidepressants may not be working, identify if you are at an increased risk of miscarriages, could suffer unnecessary complications from standard cancer treatments and if you are at a higher risk for heart attacks and strokes. What is the methylenetetrahydrofolate reductase (MTHFR) gene and what is it responsible for?
The methylenetetrahydrofolate reductase (MTHFR) gene found in all humans is responsible for providing the body with the necessary instructions to produce the enzyme methylenetetrahydrofolate reductase. As an amino acid, methylenetetrahydrofolate reductase (MTHFR) is a vital component in a cascade of chemical changes to make protein and other important compounds used by the body. Amino acids are important components to the human body responsible for providing the body with energy as well as the breakdown of food, growth and tissue repair. As you can see this gene is pretty freaking important to several health processes… which, in addition to the handy initials, is the reason I call it the ‘mother freaking’ gene.
This is a very complex sequence of events, so let’s break it down and gain a better understanding of how MTHFR functions and why it is such an important player in this chemical cascade.
MTHFR is responsible for the conversion of the molecule 5,10-methylenetetrahydrofolate to the molecule called 5-methyltetrahydrofolate, the biologically active form of folic acid or folate; the form which can be used by the body. This molecule conversion, known as methylation, is one step in the process of converting homocysteine (cysteine) into methionine- a building block of protein and other important compounds.
In other words, MTHFR is responsible for converting folic acid and folate into the usable form which is vital for folate required body functions like cell division and DNA/gene production, DNA repair and red blood cell production.
When this sequence of events does not occur properly and a person cannot adequately convert folic acid and folate into 5-methyltetrahydrofolate, this does not allow the body to further break down the chemical homocysteine; this leads to abnormally elevated homocysteine levels.
High levels of homocysteine could be negatively affecting your health. Read more to see how...
Well, when homocysteine levels are not regulated and become higher than normal, it increases a person’s risk for certain medical conditions such as:
Macular degeneration (an incurable eye condition which causes the retina to deteriorate)
Alzheimer’s disease (an abnormal form of memory loss)
Neural tube defects (abrmalities in the brain, spine or spinal cord of a growing fetus such as spina bifida or anencephaly)
Placental abruption (separation of the placenta from the uterine wall during pregnancy)
Pre-eclampsia (a serious and at times life threatening condition during pregnancy in which a woman’s blood pressure is elevated and the possible presence of organ failure)
Homocysteineuria (elevated homocysteine levels in the urine)
In addition to an elevated level of homocysteine within the body, those whom do not process folic acid and folate into useable forms for the body, may become folate deficient which increases their risk for many health conditions such as:
Megaloblastic anemia; a condition which causes the body to produce immature red blood cells which can lead low levels of circulating oxygen. This can lead to symptoms such as fatigue, body aches, pallor, lightheadedness, weakness, difficulty concentrating, irritability, headache, heart palpitations, shortness of breath and related other symptoms. Click here for more information on megaloblastic anemia.
Oral mucosa changes including tongue and oral sores
Skin changes such as skin, hair or fingernail discoloration
Reproductive abnormalities such as, neural tube defects like spina bifida, premature or low-birth-weight babies
Did you know that you could have inherited an abnormal MTHFR gene from one or both of your parents?
What is methylenetetrahydrofolate reductase (MTHFR) mutation?
Humans naturally inherit 2 copies of each gene from their biological parents with each cell containing 23 chromosomes from each parent for a total of 46. Simply put, when a gene is not functioning as intended and is abnormal it is referred to as a genetic mutation.
MHTFR genetic mutations are inherited conditions present in about 30-50% of the population, in which the mutation is passed on from one or both parents to a biological child. The genetic mutation can be present on one or both of the child’s genes and depends on if he/she inherited the mutation from one or both parents.
These mutations can cause the above mentioned enzymes not to work properly and become less efficient. In fact, depending on the type of MTGFR gene mutation a person has, genes can function less effectively by around 30-70%.
Currently, the two MGTFR mutations that are of interest are MTGFR C677T and MTGFR A1298C, which are inherited genetic changes from one or both biological parents. In the US it is estimated that the rate of having 2 copies of the C677T gene are 25% and 10-15 % in Hispanics and Caucasians respectively.
As discussed, those affected by MTHFR mutations may be at a higher risk for health complications. For example, women affected by two C677T mutations are at a higher risk of neural tube defects during pregnancy, which increases if their fetus is also affected by this double genetic mutation; their risk for pregnancy loss also increases if they have elevated homocysteine levels. It is however, not entirely clear as to the role of MTHFR mutations in the mentioned disease conditions and additional research is needed in this area. Some of your symptoms may be from a MTHFR mutation.
Symptoms of an MTHFR mutation may or may not be present, however, there are some symptoms and syndromes which may be associated to a MTHFR mutation/altered homocysteine or folic acid metabolism. Dr. Ben Lynch of MTHFR.net lists the following conditions and symptoms:
Acute Lymphoblastic Leukemia
Bone fracture risk in post-menopausal women
Chronic Fatigue Syndrome
Childhood cognitive deficits
Congenital heart defects
Decreased telomere length
Differentiated Thyroid Carcinoma
Drug, smoking and alcohol addictions
Esophageal Squamous cell carcinoma
Idiopathic male infertility
Infant depression via epigenetic processes caused by maternal depression
Irritable Bowel Syndrome
Ischemic Stroke in Children
Migraines with aura
Neural tube defects
Nitrous Oxide Toxicity
Post-menopausal breast cancer
Potential drug toxicities: methotrexate, anti-epileptics
Primary Closed Angle Glaucoma
Shortness of breath
Tetralogy of Fallot
Tight Anal Sphincters
Type 1 Diabetes
Unexplained Neurologic Disease
Additional research is needed in this area to determine the role of MTHFR in certain disease conditions, symptoms and syndromes. You may be at risk for certain health complications if you are found to have an MTHFR gene mutation.
Having a MTHFR mutation may increase a person’s risk of certain diseases and syndromes as discussed throughout this article. Those who are affected by a mutation in the MTHFR gene C677T are at a higher risk of developing certain conditions like:
Cardiovascular disease, including coronary heart disease
Elevated homocysteine levels
Neural tube defects
Whereas those affected by MTHFR A129C gene mutations are at a higher risk for developing conditions like:
It is important to note that there have been conflicting scientific results in studies evaluating MTHFR mutations and homocysteine’s effect on the development of certain medical conditions and that additional research is needed in these areas. For example, the American Heart Association does not classify a an MTHFR mutation a major risk factor for heart disease, as elevated homocysteine levels are considered a marker for heart disease, not currently understood to be an actual cause.
Up to 70% of depressed patients have a compromised ability to properly break down folic acid into the bioavailable active form that is useable by the body.
A MTHFR mutation may exacerbate the symptoms of depression by causing nutritional imbalances that cause your body to need more active folate. This may be why some depressed patients don’t see improvements from some of their antidepressant medications.
Not having enough folate may also increase your risk for a depressive relapse.
Mostover-the-counter folic acid supplements do not contain the important and necessary biologically activeform of folic acid or folate.
A consultation with your healthcare provider who understands the effects of having an MTHFR gene mutation on folic acid/folate metabolism is helpful in determining if you would benefit from a prescription medication such as Metafolin® or Deplin®. These medications contain the biologically active form of folate- L-methlfolate and may improve how your body metabolizes folate and improve your depression or other MTHFR gene mutation related symptoms.
Why test for an MTHFR mutation?
Testing for an MTHFR mutation is not something that healthcare providers routinely offer and much of its reasoning is based on antidotal evidence, however, it may be recommended in certain situations like:
Elevated homocysteine levels
A history of miscarriage
Chronic gastrointestinal conditions
Chronic anxiety or depression
In addition to the above situations, genetic testing may be recommended in people with a known family history of an MTHFR mutation or prior pregnancies with genetic abnormalities.
MTHFR mutations are not the only cause of elevated homocysteine levels. In fact, they may be elevated when there is no MTHFR mutation to be found. If the gene mutation is the suspected cause of the elevated levels of homocysteine, it will depend on the specific genetic mutation if they will be elevated at all. How to test for a MTHFR mutation?
Founding chairwoman of the Genomic Medicine Institute, Dr. Charis Eng, MD, Phd reports that while there are tests available to determine the presence of an MTHFR mutation, that a less expensive alternative to genetic testing is to test blood homocysteine levels. She notes that the results of the MTHFR testing to not guide treatment, however, homocysteine levels do.
In the case in which either a healthcare provider recommends testing or a person would like to know their gene status, there are many options on the market today and include testing blood, buccal samples and/or saliva. DNA collections can be done in the comfort of your own home or in a healthcare provider’s office and depends on the company being used.
So many choices…so many genes!
It is important to do your research on which lab and collection technique best suits your needs. If you undergo testing with a healthcare provider, insurance may cover the costs for genetic testing, however, it is important to speak with the insurance company to ensure this before proceeding. This will reduce the risk for an uncovered medical bill to cover the cost of MTHFR testing.
There are many options to performing the tests at home or through a designated laboratory. Determining which company to use is a personal decision based on many factors including location, cost, specimen collection methods and testing needs.
Here are four quick ways to test for MTHFR Gene mutation
We have complied a short list of a handful of the many labs which are available for testing as a sample of the services offered and what is to be expected.
Oral Swab Testing Labs:
Molecular Testing Labs (https://myhomemthfrtesting.com/product/mthfr/)
Collection method: 2 sterile oral swabs; self-collection at home
Turn-around time: 1 week email results
Spot blood Testing Lab:
MTHFR Gene Health (https://mthfrgenehealth.com/product/mthfr-gene-home-test-kit-2/ )
Collection method: Spot blood test with an at home lancet; self-collection at home
Turn-around time: 7-10 business days; Australia based company with international shipping options
Whole Blood Testing:
SpectraCell Laboratories (https://www.spectracell.com/patients/get-tested/ )
Collection method: Whole blood collected at an allocated blood draw site; specimen collection kit shipped to home but there is the need to have whole blood drawn by a professional lab
Turn-around time: 7-10 business days
Note: While you can order your testing kit directly from SpectraCell Laboratories, they note the following on their website: “specimens cannot be collected and lab results cannot be mailed to CA, MD, MA, NJ, NY and RI residents. Specimens will NOT be delivered to a PO Box address.”
Collection method: At home saliva collection
Turn-around time: 6-8 weeks from the time the sample is received in the laboratory
Don’t see your MTHFR results on your 23andMe report?
Here’s where that little known freebie comes in!
In order to get the MTHFR results from the data provided by 23andMe, the raw data will need to be analyzed by a 3rd party or qualified health professional. Some of these third party providers include Genomapp and GeneticGenie.
Speaking with a qualified healthcare provider is essential in determining your personal risk factors for folate deficiency, elevated homocysteine levels and the possibility of having an MTHFR genetic mutation. Having one or more of these conditions, may place you at a higher than average risk for certain medical conditions, some of which can have serious implications on yourself, your children and your family.
Maintaining the proper levels of both folate and homocysteine are important in reducing the risk of some “preventable” conditions like heart attacks, strokes, neural tube defects and more and understanding your personal risk factors may be lifesaving. While it remains unclear the actual benefit of screening the general population for the MTHFR mutation, it may be helpful in certain situations such as with recurrent miscarriages, prior genetically abnormal pregnancies, family history of MTHFR mutations, folate deficiencies, elevated homocysteine levels, chronic gastrointestinal conditions, autoimmune diseases and chronic anxiety or depression.
Speak with your healthcare provider to see if MTHFR genetic testing is right for you and how they can help to best interpret your results!
MTHFR gene. (June 20, 2017) https://ghr.nlm.nih.gov/gene/MTHFR#sourcesforpage
Can You Have a Successful Pregnancy with MTHFR? (April 4, 2017) http://www.healthline.com/health/pregnancy/mthfr#overview1
NIH: Folate. Fact Sheet for Consumers (April 20, 2016) https://ods.od.nih.gov/factsheets/Folate-Consumer/
NORD. Anemia, Megaloblastic. (no date) https://rarediseases.org/rare-diseases/anemia-megaloblastic/
NIH. MTHFR gene mutation. (May 2017) https://rarediseases.info.nih.gov/diseases/10953/mthfr-gene-mutation
MTHFR Mutation Symptoms, Diagnoses & Natural Remedies (no date) https://draxe.com/mthfr-mutation/
Liew SC, Gupta ED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. Eur J Med Genet. 2015 Jan;58(1):1-10 https://www.ncbi.nlm.nih.gov/pubmed/25449138
MTHFR Mutation, Symptoms and Diet: What You Need to Know. (May 18, 2017) https://www.dietvsdisease.org/mthfr-mutation-symptoms-and-diet/
American Macular Degeneration Foundation. What is Macular Degeneration? https://www.macular.org/what-macular-degeneration
Mayo Clinic. Diseases and Conditions
Placental abruption (December 13, 2014) http://www.mayoclinic.org/diseases-conditions/placental-abruption/basics/definition/con-20024292
Mayo Clinic Diseases and Conditions: Preecclampsia (April 21, 2017) http://www.mayoclinic.org/diseases-conditions/preeclampsia/home/ovc-20316140
Alzheimer’s Association. What Is Alzheimer's? (no date) http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp
Medline Plus. Neural Tube Defects (no date) https://medlineplus.gov/neuraltubedefects.html
Genetics Primer - Why do we have two copies of each gene? (no date) http://www.nchpeg.org/dentistry/index.php?option=com_content&view=article&id=22&Itemid=55&limitstart=2
Dr. Ben Lynch. MTHFR Mutations and the Conditions They Cause (December 6, 2012) http://mthfr.net/mthfr-mutations-and-the-conditions-they-cause/2011/09/07/
Cleveland Clinic. A Genetic Test You Don’t Need: Testing MTHFR is usually unnecessary (September 27, 2013) https://health.clevelandclinic.org/2013/09/a-genetic-test-you-dont-need/
Brustolin, R. Giugliani, and T. M. Félix. Genetics of homocysteine metabolism and associated disorders. Braz J Med Biol Res. 2010 January ; 43(1): 1–7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078648/pdf/nihms-259545.pdf