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Over the past decade or so, there has been a major spike in interest in genetics and the SNPs (“snips”) that may or may not set us up for certain conditions. As people receive their genetic test results, their doctor may have told them that they “have” MTHFR. Now, let’s start with the fact that MTHFR is not a disease or condition. If you “have” MTHFR, it means you have inherited a genetic change to this gene… an MTHFR gene mutation.

What is The MTHFR Gene?

What is MTHFR? The MTHFR acronym stands for 5,10-methylenetetrahydrofolate reductase. This gene provides the code (like a computer code) or set of instructions for the body to make an enzyme by the same name. Any time you come across a word ending with -ase in physiology or biochemistry, it refers to a type of enzyme. So, the methylenetetrahydrofolate reductase gene provides the instructions for creating the MTHFR protein, which is an enzyme.

This enzyme helps the body process certain amino acids used to create proteins in the body. MTHFR is especially used for folate metabolism. It converts folate (vitamin B9) into an “active” form that the body can use. Specifically, it converts 5,10-methylenetetrahydrofolate to the active 5-methyltetrahydrofolate. Don’t be intimidated by the long words – it’s basically a conversion of the “methylene” form to the “methyl” form by adding a hydrogen atom. This process is called methylation.

One reason methylation is significant is that it converts an amino acid called homocysteine to another amino acid called methionine. Without adequate levels of this enzyme, homocysteine can build up in the blood, leading to a diagnosis of “hyper-homocysteinemia.” This term refers to high levels of homocysteine, which can be toxic. An inability to properly convert homocysteine to methionine can result in low levels of methionine, increasing your risk for health problems, including cardiovascular disease.

What Does it Mean to “Have” MTHFR?

If you have an MTHFR mutation, you have reduced MTHFR activity. These mutations affect approximately 50% of the population. MTHFR mutations can appear in a few different forms referred to as “single nucleotide polymorphisms,” and shortened to “SNPs.” The MTHFR C677T variant is the most common, and the second most common is the A1298C. These letters and numbers refer to the position of the mutation on the chromosome. It’s like the GPS coordinates for the place on the gene.

Here’s how your SNP affects your ability to methylate. As you can see, two copies of C677T are the worst genetically. Those who have this SNP, and a poor methylation status (determined through testing and symptoms), will need the most methyl donor support:

  • C677T homozygous (2 copies): 60 to 80% reduction function
  • C677T heterozygous (1 copy): 30 to 40% reduction in function
  • A1298C heterozygous (1 copy): 20% reduction in function
  • A1298C homozygous (2 copies): 40% reduction in function

For each gene, you receive two copies –one from your mother and one for your father. For each of these polymorphisms you can either have one copy or two. If the gene were normal, you would have zero. Let’s say your mother has the mutation, but your father doesn’t (or vice versa). Then you would be heterozygous, meaning the two genes aren’t the same. However, if you received a mutated gene from both parents, you would be homozygous, meaning the two genes ARE the same.

Poor Methylation and Folic Acid: A Short History

You might wonder why it is so common for people to have poor methylation and why there’s such an apparent need for folic acid supplementation in the American population. There are a few potential reasons. The main one is that during the 20th century, our consumption of methyl donor foods (especially green leafy vegetables) went down while our toxicity went up. Taking folic acid through our supplements and in enriched and fortified foods may not be as great as we’ve been led to believe.

The Advent of Processed, Nutrient-Depleted Foods

As processed foods became popular in the 1920s and 1930s (think “Wonder Bread” and margarine), the nutrient quality and quantity went down. That led to poor methylation in the women of childbearing age. Remember this: “Sick mothers give birth to sick babies.” A mother who isn’t methylating properly before and during pregnancy is more likely to have a child who isn’t methylating properly, resulting in neural tube and other birth defects, like spina bifida.

In the 1940s, food companies started using folic acid as a part of their government-sponsored food enriching program. “All-purpose” white flour, stripped of its nutrients, was now “enriched” with synthetic vitamins and minerals. Now people could eat plenty of processed foods that were re-supplied with all the essential nutrients listed on the USDA nutrition label. The food enrichment program was initiated to combat certain diseases that had surfaced in the previous decades.

Folate Deficiency Linked to Birth Defects

When scientists in 1965 realized the connection between low folate levels and birth defects, like spina bifida, they began recommending folic acid supplementation in pregnancy. That led to doctors recommending prenatal multivitamins with high levels of folic acid to expectant mothers in the 1990s. Because folate wasn’t considered shelf-stable, the synthetic form of folate, folic acid, was used. The government also started mandating adding folic acid to fortified foods during the 1990s – primarily through cereal grains.

However, the body doesn’t handle natural and synthetic things the same. While taking folic acid may help correct a severe folate deficiency, it also slows down all the other metabolic pathways the original nutrient (folate) is trying to accomplish. Ultimately, that means taking folic acid DECREASES your methylation! – that then leads to other birth defects, even “genetic” defects, like Down Syndrome.

Folic Acid Does More Harm Than Good

Folic acid should be avoided as much as possible – in multivitamins and supplements, baking ingredients, and especially processed food. Why? Because the body has a difficult time metabolizing it. Researchers have now linked “un-metabolized folic acid syndrome” (UMFA) to colorectal and prostate cancers.

Rather than the run-of-the-mill folic acid supplement, seek out methyl folate or folinic acid (leucovorin). The idea behind increasing folic acid is good; the form is not good. Now, back to our discussion of methylation.

What is Methylation?

On the greater scale, methylation also serves as one of our body’s natural detoxification processes that occur daily. What do you need to detoxify? Everything from food additives to pesticides to alcohol to micro-organisms. You also need to detoxify the metabolic end products produced as a part of normal bodily functions. Methylation is a part of phase I liver detoxification, and it has specific nutrient requirements, such as antioxidants, vitamin C, vitamin E, and B vitamins, including folate. Your ability to use folate for methylation and detoxification, in general, is based on your ability to use the MTHFR enzyme. However, methylation does much more than control detoxification.

Many enzymes and proteins in the body are created in an “inactive” form. Methylation is the process of adding a methyl group (a carbon surrounded by hydrogens) to that protein or enzyme so that it is activated at the right time and in the right place. Methylation not only activates detox pathways but also activates enzymes, neurotransmitters, cholesterol, and even DNA. As a result, methylation affects every system of the body and can impact a wide variety of diseases and conditions.

Who Are The Major Players in Methylation?

Methylation doesn’t happen by folate alone. Certain cofactors or “helper molecules” are also needed to work alongside folate (vitamin B9). Just a few of these include:

  • Vitamin B6 (pyridoxine)
  • Vitamin B12 (cobalamin)
  • SAMe – S-adenosylmethionine (SAMe). SAMe is a form of methionine that is needed for methylation to occur.
  • FAD – Flavin Adenine Dinucleotide (FAD) is a form of Vitamin B2 (Riboflavin).
  • NADP – NADP is a coenzyme of Vitamin B3 (Niacin) that contributes to the methylation process.

As you can see, the B vitamins work together to make this process happen. Beyond nutrients, whether you methylate well is most influenced by the same three categories of stressors: traumas, toxins, and thoughts. Emotional trauma, injuries, infections, and stress can all influence your ability to methylate. These physical, biochemical, and emotional disruptors can swing your methylation balance either way: toward undermethylation or toward over methylation. In this article, we are focusing on undermethylation.

Signs & Symptoms of Undermethylation

Undermethylation, also called “hypomethylation,” can show up with a variety of signs and symptoms:

  • Fatigue
  • Depression
  • Difficulty concentrating
  • Headaches
  • Scoliosis and facial asymmetry
  • Tongue- and lip ties
  • Digestive Issues
  • Hormonal imbalance/fertility issues
  • Feeling terrible doing detox programs
  • Insomnia
  • Allergies
  • Poor pain tolerance
  • Obsessive-compulsive tendencies
  • History of perfectionism and/or high accomplishment

These signs and symptoms can also indicate other health susceptibilities and conditions, so it’s important to do testing, like gut health testing, immune testing, and others.

Continue to Part 2…


  1. MTHFR gene: MedlinePlus Genetics
  2. Folic Acid Food Fortification—Its History, Effect, Concerns, and Future Directions – PMC (
  3. MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series – PMC (
  4. DNA methylation, cancer susceptibility, and nutrient interactions – PubMed (
  5. DNA methylation and cancer – PubMed (
  6. S-Adenosylmethionine and methylation – PubMed (
  7. Structural insight into inhibitors of flavin adenine dinucleotide-dependent lysine demethylases – PubMed (
  8. NADP (Coenzyme) – an overview | ScienceDirect Topics



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Disclaimer: This content is for educational purposes only. It’s not intended as a substitute for the advice provided by your Wellness Way clinic or personal physician, especially if currently taking prescription or over-the-counter medications. Pregnant women, in particular, should seek the advice of a physician before trying any herb or supplement listed on this website. Always speak with your individual clinic before adding any medication, herb, or nutritional supplement to your health protocol. Information and statements regarding dietary supplements have not been evaluated by the FDA and are not intended to diagnose, treat, cure, or prevent any disease.

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