The Common MTHFR DNA Mutation: a Risk Factor for Many Chronic Physical and Mental Diseases

 

What is an MTHFR DNA mutation?

 Please understand that this is a very simplistic explanation of a very complex problem.

 In 2003, with the completion of the Human Genome Project, it was discovered that a relatively high level of the population had mutations in the methylenetetrahydrofolate reductase (MTHFR) genes.  These are very important genes related to our health.  Mutations of these genes have been implicated in increasing the risk of heart disease, Alzheimer’s and dementia, neural tube defects, colon cancer, leukemia, breast cancer, prostate cancer, mood disorders and schizophrenia, autistic spectrum disorders, neuropathy and other nervous system disorders, chronic fatigue, fibromyalgia, irritable and inflammatory bowel syndrome, miscarriages, migraines, chemical sensitivities, elevated levels of toxins which increase other diseases, and more.

 

The MTHFR gene is the code to create the MTHFR enzyme.  This enzyme is important in the methylation cycle, which happens in every cell in our body.  MTHFR adds a methyl group (-CH3) to folate and B-12 to create the activated forms of these B-vitamins:  5-MTHF (methylfolate) and methylcobalamine. 

The active forms of folate and B-12 are used in many functions in the body.  The most commonly noted is how they are used to convert the amino acid homocysteine down to the essential amino acid methionine, which is used by the body to make proteins, utilize antioxidants, assist the liver to process fats, assist in the detoxification process, etc.   Low methionine has been linked to depression and inflammation.  Methionine also helps convert estradiol (E2) into estriol (E2), the estrogen most prevalent in a pre-menopausal woman, and least likely to cause cancers.

Methionine is converted into SAM-e, which is anti-inflammatory, supports the immune system, helps produce and break down serotonin, dopamine and melatonin, and is involved in the growth, repair and maintenance of your cells.

 

When homocysteine cannot be converted to methionine because of the lack of 5-MTHF and methylcobalamine, the levels of homocysteine rise.  Homocysteine irritates the lining of the arteries and increases risk of heart attacks and stroke.

 These vitamins are also necessary in creating neurotransmitters, in forming a healthy central nervous system in the fetus, red blood cell formation, synthesis and function of nerve tissues such as myelin, energy production from the Kreb cycle, and much more.

 Testing for the mutation is usually done through a blood test, though 23andme and other genetic testing companies use a saliva sample.  As yet, health insurance does not usually pay for the testing, at least in Utah.

 There are at least 30 genetic SNPs that affect the MTHFR enzyme, but the greatest effect seems to be from 2 genes: C677 or A1298.  Each gene carries 2 strands, one from each parent.  If only one strand of one gene is mutated, it is called “heterozygous.”  If both strands of one gene are mutated, it is called “homozygous.”  Approximately 40% of the population is heterozygous for one gene.  This often causes minimal symptoms when younger, but still increases the risk of chronic diseases with age.  A person who is homozygous for one gene has an increased deficit and will often show symptoms earlier in life.  Most of those who are homozygous for both genes do not survive fetal life. If a person is heterozygous for both genes it can reduce the methylation process by up to 70-80%.

About 10% of the North American population are homozygous for the C677 gene.  The risk is higher for those of Mediterranean/Hispanic descent, and less for those of African descent.  This population will generally have elevated homocysteine, and are at increased risk for heart disease, stroke, certain leukemias and colon cancer.  There is also an increased risk of schizophrenia, dementia and Alzheimer’s.

The A1298 mutation does not seem to affect the MTHFR enzyme or increase homocysteine levels.  It does, however, affect the conversion of MTHF to BH4, an important cofactor in the production of neurotransmitters, synthesis of the important nitric oxide, and detoxification of ammonia.

 Treatment for the MTHFR mutations

 A genetic mutation cannot be fixed, but the nutrients that cannot be created by the body can be given in the form of supplements.  The most important are providing the activated forms of folate and B-12 that are already methylated, since the body is unable to do that well.

When a body has been depleted of adequate amounts of activated folate and B-12, often toxins have built up.  Sometimes if high levels of these vitamins are taken negative symptoms occur because the body starts detoxing heavily.  We recommend starting slowly and building up, and if you suspect high levels of heavy metals or other toxins see your integrative health care practitioner for testing and specific detox protocols.

We recognize that diet is all important, especially eating whole rather than processed foods, which support how the genes are expressed.  Processed foods also often have folic acid as an additive, which can make the problem worse. 

We often start our patients on the multivitamin-mineral supplement SpringTree SuperMulti Plus, which has 1000 mcg each of 5 MTHF and methylcobalamine, along with many co-factors that assist with their function.  Only a very small percentage react negatively to that amount with symptoms of over-methylation (irritability, depression, anxiety, sore muscles, headaches, joint pain, migraines, rash, acne, heart palpitations, nausea, insomnia).  SuperMulti Plus is also a good supplement to use when you know you have a mutation but have no symptoms, to assist in preventing future problems.

If there are no negative effects from SuperMulti Plus, we may add the supplement SpringTree Methylation Factors, which includes the activated B-vitamins, B-6, trimethylglycine (another methyl donor) and added ingredients to reduce the risk of becoming over-methylated.  Depending on the severity of the mutation and the symptoms of the patient, we can have the patient take 1 to 3 or more capsules per day.

SpringTree Methylation Factors

At $24.95 per 90-count bottle, Methylation Factors is probably the least expensive high quality methylation supplement on the market.  It has added ingredients most other methylation supplements don’t have with the goal to improve the breakdown of the methyl products after they are used to reduce the risk of over-methylation.

Each capsule contains:

·         5-MTHF 1000 mcg—the activated form of folate
·         Methylcobalamine 1000 mcg—the activated form of B-12
·         Pyridoxyl-5-Phosphate                 25 mg—the activated, methylated form of B-6, often necessary in the cell’s utilization of B-12 and folate
·         Betaine Anhydrous (Trimethylglycine) 250 mg—a methyl donor
·         Riboflavin 25 mg—low levels of riboflavin may interfere with the metabolism of folate, particularly in individuals homozygous for the MTHFR C677T gene variant
·         Zinc  5 mg—many of the enzyme processes utilizing B-12 and folate are zinc dependent
·         Inositol Hexanicotinate (non-flush niacin) 25 mg—used in breaking down methyl products after they have been used; reduces the “over-methylation” effects
·         N-acetyl-cysteine 100 mg—the precursor of glutathione, more absorbable and less expensive than glutathione itself.  An MTHFR mutation may reduce the production of glutathione, the body’s most powerful anti-oxidant and detoxifier.  Increased glutathione also reduces the “over-methylation” effects by both means—reducing oxidation and detoxifying.
·         Tumeric  100 mg—many people with MTHFR mutations have high levels of inflammation which increase the risk of side effects from methylation products.  Tumeric has been shown to reduce inflammation and prevent increased pain.
·         Milk Thistle Extract 150 mg—supports the liver through the increased detoxification that comes with taking the methylated vitamins.
·         Potassium 50 mg—restoring  B-12 after long-term deficiency can cause potassium deficiency because as B-12 is restored, the body starts making more blood cells, and this process uses up potassium, increasing muscle pain and spasms.

Caution is advised to start slow and increase slowly.  If one capsule causes symptoms, start with just a methylcobalamine supplement to get the body used to the methylation.  Some people need higher levels of niacin to break down the extra methyl products.  Work with an integrative health care practitioner that is knowledgeable in the MTHFR mutations.  With care the great majority of people with these mutations can improve in health and well-being.