MTHFR genetic defect – what it is and how it can affect you
In 2003, a genetic study called the Human Genome Project was completed. And via that study, they discovered that an important gene towards your health and well-being, called the methylenetetrahydrofolate reductase (MTHFR), was defective in a lot of folks!
When it’s all working right, the MTHFR gene begins a multi-step chemical breakdown process, aka methylation, which in simplified terms, is like this:
- The MTHFR gene produces the MTHFR enzyme.
- The MTHFR enzyme works with the folate vitamins (B9, folic acid), breaking it down from 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate
- 5-methyltetrahydrofolate helps convert the amino acid homocysteine down to another essential amino acid, methionine, which is used by your body to make proteins, utilize antioxidants, and to assist your liver to process fats. Methionine helps with depression and even inflammation. It also helps convert estradiol (E2) into estriol (E3)!
- Methionine is converted in your liver into SAM-e (s-adenosylmethionine), which is anti-inflammatory, supports your immune system, helps produce then breakdown of your brain chemicals serotonin, dopamine and melatonin, and is involved in the growth, repair and maintenance of your cells.
- i.e. a proper methylation pathway like the above is going to mean you will have a better chance in eliminating toxins and heavy metals, which can reduce your risk for cancer and other health issues, and put less stress on your adrenals.
What a defective (mutated) MTHFR gene does to you
- It produces a defective MTHFR enzyme of different varieties i.e. it functions less than optimally, such as performing at only 40% of its capacity, or 70% of its capacity. It can mean you won’t break down toxins or heavy metals well i.e. you could find yourself with high iron, or high copper, or high lead, or high mercury….etc. High copper can also cause low ferritin, even though your iron levels look great!
- The defective enzyme doesn’t break down folate vitamins properly (of which folic acid is the precursor to), which can cause high homocysteine, which can increase your risk of coronary heart disease (arteriosclerotic vascular disease or venous thrombosis), and related heart and BP conditions, as well as increasing your risk for dementia.
- Homocysteine is poorly converted to glutathione, which is your body’s chief antioxidant and detoxifier. You are then more susceptible to stress and toxin buildup.
- Homocysteine is poorly converted to methionine, and less methionine can raise your risk of arteriosclerosis, fatty liver degenerative disease, anemia (see Wiki), increased inflammation, increased free radical damage… and produce less SAM-e
- Less SAM-e can increase depression
- And more broadly, an MTHFR defect can increase your risk of a variety of cancers (including breast and prostate cancer), stroke, heart problems, congenital defects, depression, IBS (irritable bowel syndrome), miscarriages, migraines, chemical sensitivities and many conditions.
- You can find yourself with high folate or high B12 i.e. your body will have problems converting inactive forms of folate and B12 to the active forms. So the inactive folate or B12 will simply build up in your serum, also inhibiting the active forms. Most serum folate tests are actually measuring folic acid, which needed to be converted to methylfolate to be used metabolically.
- The journal Molecular Psychiatry states that “Schizophrenia-like syndromes, bipolar disorder, Parkinson’s disease, Alzheimer’s disease and vascular dementia have all been associated with one or more mutations of the MTHFR gene”. (2006;11, 352–360)
More than one mutation of the MTHFR gene
Genes are passed down by your mother and your father. Most literature states there are a good 40-50 different mutations of this important gene which could be passed down by one, or both or your parents. But only two are particularly problematic: mutations on the points at C677T and A1298C. The numbers refer to their location on the MTHFR gene. You will also sometimes just see them written as just 677 and 1298.
There are many combinations of MTHFR:
- Homozygous: means you have both copies of either the 677 mutation, or the 1298 mutation, one from from each parent.
- Heterozygous: means you have one copy of either the 677 mutation, or the 1298 mutation, plus a normal one from the other parent.
- Compound Heterozygous: means you have one copy of the 677 mutation from one parent and one copy of the 1298 mutation from the other parent.
- Triple homozygous mutations (more rare): an example would be one C677T, one A1298C, and a P39P or R594Q, for example.
Here are possible combinations:
- Normal/Normal for both 677 and 1298
- Heterozygous 1298 / Normal 677 (i.e. one parent passed down a single 1298 mutation)
- Homozygous 1298 / Normal 677 (i.e. both parents passed down the 1298 mutation)
- Heterozygous 677 / Normal 1298 (i.e. one parent passed down a single 677 mutation)
- Homozygous 677 / Normal 1298 (i.e. both parents passed down the 677 mutation)
- Heterozygous 677 / Homozygous 1298 (one parent passed down the 677 mutation; both passed down the 1298)
- Homozygous 677 / Heterozygous 1298 (both parents passed down the 677 mutation; one passed down the 1298)
- Heterozygous 677 / Heterozygous 1298 (Compound Heterozygous: one parent passed 677; one passed 1298)
- Homozygous 677 / Homozygous 1298 (Compound Homozygous, meaning you have two 677, two 1298)
Are you overwhelmed yet?
Dr. Amy Yasko will test about 30 methylation SNP’s (single nucleotide polymorphisms), here. You may need a doctor’s prescription. It is considered to be a highly accurate test.
A similar one you can do on your own with saliva is from 23andme. It is stated to miss 5 SNP’s that Yasko’s will not miss, but is cheaper and still an excellent test. NOTE: as of October 2015, 23andme went up from around $100 to $199. Sad.
After the 23andme results come back, you’ll get “raw data”. You will upload that data to any of the following, which in turn will give you what you need:
- Genetic Genie, which will look at your methylation genetics just by reading your 23andMe raw data.
- Live Wello, which gives a great deal of information to you based on 23and me, plus links to learn more about each gene’s potential problem.
- Nutrahacker will tell you what supplements you need to take, and which ones plus more you need to avoid, due to your mutations. It’s very interesting!
- Sterling Hill’s app http://www.mthfrsupport.com/
sterlings-app/ or you can contact her and pay for a call to help with interpretation of your genetics.
A VAST amount of genetic information can be obtained from www.promethease.com
Another informative test is the NutrEval, which will test your antioxidants, B Vitamins, digestive support, essential fatty acids, and minerals, plus amino acids via a urine collection.
Here’s a good string about testing methyl pathways vs genome testing.
How to treat it
You can’t change a defective gene. But you can help it do its job better and minimize problems.
Some find their ‘folic acid’ lab test levels are high (it’s one of several folate vitamins) since a defect in the gene prevents your body from using it, so it goes high…unused. The recommended solution is avoid supplements and many processed foods with folic acid, especially if you are Homozygous (having a copy of the same defective gene from each parent). Healthy foods that contain folate should be okay, as would be the active form of folate called methylfolate as a supplement, also called 5-MTHF (5-methyltetrahydrofolate).
B12 might also be high, so patients tend to avoid the synthetic supplemental version of B12 called cyanocobalamin and instead favor the more useable methylcobalamin (methylB12), which will help break down those high levels. But the methylB12 will be used by your body in detoxing you from toxins, so you may need to start low to avoid detox side effects like fatigue, achiness, etc.
Another good B-vitamin is the methyl version of B6, called P-5-P.
Dr. Ben Lynch feels that “repairing the digestive system and optimizing the flora should be one of the first steps in correcting methylation deficiency”, and that especially includes treating candida because of the toxins it releases, inhibiting proper methylation.
Some experts recommend eating clean, such as Paleo or the GAPS diet.
Avoiding exposure to toxins is important! Look at your household clean supplies, for example.
If adding methyl B’s cause you to over-methylate, taking time-released Niacin, 50 mg, can slow it down. Symptoms of over-methylation can include muscle pain or headaches, fatigue, insomnia, irritability or anxiety.
Minerals play a key role in several enzymatic functions. Vitamin C helps reduce oxidants. Molybdenum (500 mcg) helps break down excess sulfates and sulfites
This website http://www.knowyourgenetics.com/ offers suggestions on how to treat your defects.
***And here’s a REALLY NEAT website to upload your 23andme raw data to because it tells you what supplements to take and/or avoid: https://www.nutrahacker.com/
High Copper/Low zinc
This can be a common finding when you have an MTHFR defect–a high level of copper, which will conversely mean your zinc levels will fall. And since the ratio of these two metals is highly important, correctly the problem is crucial, since high copper can be related to hyperactivity, depression, headaches, acne, frequent colds due to lowered immunity, sensitive skin and/or bruising, worsening hypothyroid, adrenal stress and more.
High copper can also make it difficult to raise iron levels, including your ferritin.
Vitamin C is known to help lower high levels of copper via detoxing, but patients report they need to go low and slow to tolerate the detoxing. Zinc is also used the same way–to encourage the lowering of copper, but the same caution with detoxing applies. Lawrence Wilson, MD recommends a nutritional approach to correcting the imbalance: remove IUD’s, avoid high copper foods like chocolate, seeds and avocados, avoid stress and more. Work with your doctor.
Are there other mutations to be aware of?
Yes, and one is called a CBS mutation. When doing its job correctly, the CBS gene will convert homocysteine into cystathionine, and this pathway removes sulfur containing amino acids. When it’s not doing its job correctly, you could have an excess of sulphur, which can cause kidney damage. Experts strongly recommend avoiding processed foods if you have this mutation, since they can have high amounts of sulphur. This mutation can also cause low serotonin and dopamine, and make you sensitive to chemicals.
Conversely, one can have an elevated, “up-regulated” CBS pathway, resulting in excess ammonia, urinary sulfates, and lowered breakdown of glutathione. (Janie has that one)
Read Mary’s story.
Have your own story? Send it to Janie using the Contact below!
More to read
A map of all the possible methylation pathways.
Dr. Ben Lynch’s MTHFR website with forums, too.
National Library of Medicine MTHFR information page
Lab paper on MTHFR mutation, especially related to its effect on your heart, and more.
Informative MTHFR Support website— Also has forum.
Detailed notes this mother took about MTHFR and methylation from a Dr. Ben Lynch lecture.
Other gene mutations like CBS that need to be address
What does SNP mean??
As you get to reading about all your genes, you may see the acronym SNP used a lot (sounds like snip). It stands for Single Nucleotide Polymorphism. And SNP is basically another word for a mutation in your gene.