An MTHFR gene is a genetic component of the “folate cycle” and is responsible for the conversion of folate from your diet and or supplements into an active form of folate that the body uses and needs as an essential nutrient, in other words, you can’t live without it.
MTHFR is short for Methylene tetrahydrofolate reductase (MTHFR). MTHFR’s job is to break down via its enzymes the conversion of 5-10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, also known as 5-MTHF or “methyl folate” or “activated folate”.
When this gene has “mutations” that are “active” gene mutations, this can result in a loss of function in your ability to convert your folate from your diet or supplements to make “activated folate”. As per the below image, you can see homozygous MTHFR, (double copies of gene mutations in red):
This is a big problem; it means you don’t get enough folate into your body’s cells and the problem can cause a chain reaction of many other problems including physical and mental health problems. You effectively have a folate deficiency no matter how much you eat or supplement folate.
Folate (vitamin B9) deficiency or MTHFR gene mutation symptoms
- Addictive behaviors
- Cardiovascular disease – Heart attack, atherosclerosis, elevated cholesterol, hypertension,
stroke, fat metabolism issues
- Chemical sensitivity
- Chronic fatigue syndrome
- Chronic viral infection
- Cleft palate
- Congenital Heart defects
- Downs syndrome
- Immune deficiency
- MS (multiple sclerosis)
- Neural tube defects
- Nutritional disorders (Vitamin & mineral imbalances that lead to disease)
- Panic attacks
- Pulmonary embolisms
- Recurrent miscarriage
- Spina bifida
- Thyroid dysfunction
As you can see this one gene mutation can cause serious health problems, but it doesn’t stop there. When you have a nutritional break in folate, the bigger problem is that folate works with all other B complex vitamins.
As you can imagine, just having active gene mutations in MTHFR can lead to a cascade of nutritional breaks in all B complex vitamins and it gets more complex, this is because B complex vitamins work with hundreds of other biochemical reactions in the body and brain.
What is folate?
Folate is Vitamin B9 and is NOT the same as folic acid. (Folic acid is synthetic and is not found in nature. It must undergo various transformations for utilization.)
Folate is required for the following:
- Synthesis of nucleic acids (for DNA production and repair and tRNA
- Single carbon metabolism (methylation)
- Interconversion of amino acids (for neurotransmitter production and detoxification)
- Formation and maturation of RBC, WBC and platelet production.
- Essential for detoxification of homocysteine
For all the above functions to happen the body needs to convert folate to the active 5-MTHF (5-methyltetrahydrofolate) with the help of a number of nutritional co-factors.
This process is known as methylation. Many factors can affect methylation, however, the MTHFR gene mutation is a critical one.
What is MTHFR?
MTHFR is a gene, which produces the methylenetetrahydrofolate reductase (MTHFR) enzyme. This produces the final form of folate 5-MTHF and provides the substrate for the transmethylation cycle and is found inside each cell.
The MTHFR Genes
SNPs that we currently test for:
1. MTHFR C677T
2. MTHFR A1298C
Types of gene mutations:
Heterozygous = 1 copy of the gene from either parent
Homozygous = 1 copy of the gene from each parent (most commonly – some exceptions)
MTHFR gene mutations and loss of function
MTHFR C677T Heterozygous = 40% loss of function
MTHFR C677T Homozygous = 70% loss of function
MTHFR A1298C Heterozygous = (loss of function – research not known)
MTHFR A1298C Homozygous = between 50-70%
MTHFR C677T & MTHFR A1298C heterozygous = compound heterozygous = 50% loss of function
What happens if MTHFR prodction is reduced?
1. 5-MTHF levels go down.
2. All tissues except the liver and kidney show effects of decreased methylation which leads to:
- Decreased neurotransmitter production
- Deficiency in glutathione
3. BHMT becomes depleted in choline which causes:
- Homocysteine levels to rise
- Methylation in the liver and kidneys decrease
- Phosphatidylcholine production drops causing cell membrane and myelin instability causing
- Neuropathy and Parkinson’s type conditions
Current MTHFR testing
Testing for the gene MTHFR can be done in pathology or with a home test kit, see more information
about testing here.
What to do once you are confirmed with the mutation in the MTHFR gene.
1. Avoid all sources of folic acid. If homozygous to C677T , that includes commercial bread which is
fortified with folic acid.
2. Seek professional advice as to how to bring the methylation cycle back into balance here.
MTHFR doesn’t work alone!
MTHFR is just a small part of this cycle and although restoring the deficiency due to MTHFR gene
mutation may help most people, but this may not be the solution for everyone.
3. Only the 5-MTHF active folate should be given after consultation with an MTHFR practitioner.
4. Avoid drugs that affect the methylation cycle:
- Antacids (deplete B12)
- Cholestyramine (deplete cobalamin and folate absorption)
- Colestipol (decrease cobalamin and folate absorption)
- Methotrexade (inhibits DHFR)
- Nitrous oxide (inactivates MS)
- High dose Niacin (depletes SAMe and limits pyridoxal kinase – active B6)
- Theophylline (limits pyridoxal kinase = active B6)
- Cyclosporin A (decreases renal function and increases Hcy)
- Metformin (decreases cobalamin absorption)
- Phenytoin (folate antagonist)
- Oral contraceptives ( deplete folate)
- Antimalarials JPC-2056, Pyrimethamine, Proguanil (inhibits DHFR)
- Antibiotic Trimethoprim (inhibits DHFR)
- Ethanol (depletes folate and cobalamin)
- Bactrim (inhibits DHFR)
- Sulfasalazine (inhibits DHFR)
- Triamterene (inhibits DHFR)
6. Avoid drugs that raise homocysteine levels.
A number of prescription drugs and natural compounds can elevate blood levels of homocysteine by
interfering with folate absorption or metabolism of homocysteine. These include:
- Caffeine – Cafcit®, Cafergot®, Esgic®, Excedrin Migraine®, Fioricet, Fiorinal, Norgesic®,
- Cholestyramine – Questran®, Questran Light®, Cholybar®
- Colestipol – Cholestid®
- Fenofibrate Antara®, Fenoglide®, Lipfen®, Lofibra®, Tricor®, Trilpix®
- Levadopa Parcopa®, Sinemet®, Stalevo®
- Metformin ActoPlus Met®, Avandamet®, Fortamet®, Glucophage®, Glucovance,
Glumetza®, Janumet® Metaglip®,Prandimet, Riomet®
- Methotrexate Rheumatrex®
- Niacin Advicor®, Ocuvite, CardioBasics®, CitraNatal®, Heplive®,Niaspan, Simcor®
- Nitrous oxide
- Pemetrexed Alimta®
- Phenytoin Dilantin®, Phenytek®
- Pyrimethamine Daraprim®, Fansidar®
- Sulfasalazine Asulfidine®
7. Ask questions, get informed, and get educated by MTHFR practitioners here.