by Catherine M. Haug, Aug 12, 2017; updated May 4, 2019
The MTHFR gene is important because it is involved in the necessary conversion of one amino acid to another: from homocysteine to methionine. The gene mutation means this conversion is not made in our bodies, so we must rely on increasing dietary methionine and the dietary changes to provide sufficient methionine. [I discuss this in more detail later in this article].
Symptoms resulting from this gene mutation include: lingering fatigue, fogginess, anxiety, sleep issues and inability to deal with alcohol and other toxins effectively. (paraphrase of a quote from Dr. Doni Wilson, 4).
The mutation can result in a buildup of homocysteine, which is associated “with a higher risk in cardiovascular disease. This also affects the conversion to glutathione, which the body needs to remove waste and which is a potent antioxidant.” (4)
One important thing you can do to avoid most of the consequences of this mutation, is to avoid supplemental “folic acid,” which is a synthetic and mostly inactive form of vitamin B9 (folate). Instead, look for supplements that contain “methyl-folate.” Because the mutation also affects vitamins B6 (pyridoxine) and B-12 (cobalamine), look for supplements that contain the methyl-versions of these vitamins as well.
- Includes: 1. More about the MTHFR gene and gene mutations; 2. Recommendations from Chris Masterjohn, Ph.D.
- See also: 1. Diet and Health Menu;
More about the MTHFR gene and gene mutations
The MTHFR gene provides instructions for making an enzyme called methylene-tetra-hydro-folate reductase, which plays a role in processing amino acids (the building blocks of proteins). It is important for a chemical reaction involving forms of the vitamin folate (also called vitamin B9). Specifically, this enzyme converts (3):
- from an inactive form of folate (5,10-methylene-tetra-hydro-folate)
- to an active form (5-methyl-tetra-hydro-folate).
Or more simply stated, it adds a methyl group to folate (vitamin B9) to make it usable by the body. (4)
This reaction, in turn, is required for the multistep process that converts the amino acid homocysteine to another amino acid, methionine. (3)
Unfortunately, some of us have a mutation of the MTHFR gene, that causes serious problems. The following is a quote from Dr Izabella Wentz, as copied by Wellness Mama (9):
Individuals with low activity of the MTHFR enzyme may present with elevated homocysteine levels, which have been associated with inflammation and heart disease, birth defects, difficult pregnancies, and potentially an impaired ability to detoxify.
Nutrient deficiencies in Folate, B6 and B12 have been associated with elevated homocysteine.
Individuals with the MTHFR gene actually have a difficult time processing folic acid that is present in most cheap supplements and added to processed foods. Some professionals claim that this type of folic acid may even cause a build-up in the body leading to toxicity. Studies have been done that showed folic acid supplements increased cancer risk… one more reason to ditch processed foods and your multivitamin!
There are several different variations on the MTHFR gene mutation, which I do not discuss here; see Wellness Mama’s posting (4) for more about this.
See also Dr. Axe’s article: MTHFR Mutation Symptoms, Diagnoses & Natural Remedies (5)
Recommendations from Chris Masterjohn, Ph.D.:
The following is from Chris Masterjohn (via his newsletter):
“I’ve just put together my recommendations for MTHFR mutations in my podcast this week. But, the podcast is 2 hours long, so here’s a quick reference.
MTHFR is an enzyme that uses folate (vitamin B9) to support the process of methylation, which is used to synthesize creatine and phosphatidylcholine, regulate gene expression and neurotransmitter metabolism, and carry out dozens of other processes. Mutations are associated with cardiovascular disease, cancer, pregnancy complications, birth defects, neurological disorders and psychiatric disorders.
There’s a good chance you have an MTHFR mutation. In some populations, the percentage of people who do not have either at least one C677T mutation or one A1298C mutation is only 15%!
Most of the evidence is on the homozygous C677T mutation because it’s the strongest variant. But actually the mutations simply cause a graded decrease in activity. One A1298C mutation decreases activity by 17%. One C677T decreases it 33%. Two A198C decrease it by 39%. One of each decreases it 53%. Two C677T decrease it by 75%.
So, two things are clear. First, having at least one of these is so common that this should just be viewed as a variation in metabolism that requires different dietary emphasis, not any kind of disorder or defect. Second, the degree to which you need to follow my recommendations below increases in proportion to the level of decrease in your enzymatic activity. And even your genes are operating in the context of a complex physiology. The numbers above are averages. So you don’t need to follow everything, but testing with my blood test recommendations and testing against your symptoms and sense of well being should help you how strictly you should following them.
How to Know If You Have an MTHFR Mutation
[Dr Masterjohn recommends] getting 23andMe Health and Ancestry and then running your raw data through StrateGene (2B).
A Dietary Strategy for MTHFR Polymorphisms
1) Get the RDA for folate from non-fortified whole foods.
- For adults and children 14 years and older, the RDA is 400 micrograms, except that it is 600 for pregnant and lactating women, regardless of age.
- For children, the RDA increases from 65 micrograms in the first six months, to 80 in the second six months, 150 for 1-3-year-olds, 200 for 4-8-year-olds, and 300 for 9-13-year-olds.
- Feel free to use (as an adult, not for children), 400 or 600 micrograms per day of a methyl-folate supplement, providing you are adding it to a folate-rich diet rather than using it to replace food folate. I recommend Jarrow Methyl Folate based on cost, dose, and the fact that it is otherwise the same high-quality product as sold by other manufacturers in more expensive, higher-dose supplements.
2) Consume at least the RDA for protein.
- The RDA for protein is 0.36 grams per pound bodyweight.
- Most people need more than this for other reasons, such as optimizing body composition, preventing loss of lean mass during weight loss, reaching satiety to manage energy intake, or reaching athletic goals. You may need one gram per pound body weight or more, depending on your goals, but the RDA is adequate to support the methylation pathway.
- [Cat’s Note: from Broken Brain Docu-Series (by Dr. Mark Hyman), I learned that 30-40 g protein is ideal for each of 3 meals in the day. It’s important to even-out your protein all day, rather than low protein for breakfast, moderate or low for lunch and high for dinner, which is the usual consumption for Americans. Eating the same amount for each meal evens out your carb intake, avoiding insulin spikes and inflammatory damage to tissues, especially the brain.]
3) Get 3 grams of creatine per day.
- 1-2 pounds of muscle meat or fish (but not organ meats, eggs, dairy, or plant proteins) will supply on average 3 grams of creatine. [Cat’s note: 1-2 pounds is a lot of meat for one day. For example 1 – 2 pounds of beef steak provide 112 – 224 g protein per day (at 7 g protein per ounce of steak) or 37 – 75 g protein/meal, 1.2 – 1.9 times the recommended 30 – 40 g/meal (from Broken Brain). That means you need to get part of your creatine from supplements (see below).]
- Large volumes of muscle protein may be undesirable for someone with an MTHFR mutation because it could exacerbate the loss of glycine.
- Alternatively, you can supplement with 3 grams of creatine (or 5, if you wish, the standard maintenance dose for athletes). I’m currently using Optimum Nutrition Micronized Creatine Powder (2C).
4) Consume 900-1200 mg/d choline.
- This can be obtained by eating 4-5 egg yolks per day.
- You can substitute 100 grams [0.22 pounds] of liver for two egg yolks.
- You can meet this choline amount by eating a very large volume of low-carbohydrate plant foods. See Meeting the Choline Requirement (2D) for more details.
- You can supplement with phosphatidylcholine, but be careful of the labeling. Usually the supplement lists the phosphatidylcholine, and not the choline yield. A 420 mg capsule of phosphatidylcholine only provides 55 mg of choline, which means you’d have to take 22 capsules per day to get 1200 mg. On the basis of quality, soy-free status, and good feedback from others about the taste, I recommend Micro Ingredients Sunflower Lecithin (2E). Although the choline content is not guaranteed, on the basis of this paper (2F)I recommend consuming four to five tablespoons per day to reach the recommended choline yield.
- If you find that memory loss, poor cognitive function, or weakness are your primary symptoms of concern, consider using alpha-GPC (2G) for your choline at the same dose. This form is more effective at converting to acetylcholine, a neurotransmitter involved in neuromuscular function.
5) Boost your glycine intake.
- At a minimum, use the skin and bones of the animals you eat. For example, eat chicken with the skin instead of without. Use the bones to make bone broth. If you eat canned fish, get the fish with edible bones.
- Consider supplementing with glycine. I recommend using between 1/2 serving and 3 servings of Vital Proteins Marine Collagen (2H), on the basis that it has a much higher glycine content than beef hide products made by the same company or others with a similar devotion to quality and cleanness of source.
- [Cat’s note: see also my article How to detox glyphosate (Roundup) from your body, because glyphosate can occupy glycine’s place in proteins, causing much trouble.]
6) Be careful with SAMe. SAMe supplements support methylation, but MTHFR mutations increase the use of glycine to buffer SAMe levels, even when you don’t have enough. While I do not make a blanket recommendation against supplementing with SAMe, I caution against its use in this context because it could aggravate the loss of glycine. If you use it, be careful, and consider monitoring your glycine levels (see recommended lab tests below).
Lab Tests Recommended for MTHFR Polymorphisms
1) Homocysteine. Available from LabCorp, Quest, and the Genova ION panel, aim to keep your numbers between 6 and 9, rather than the larger range on the report.
2) Plasma or serum folate. Available from Quest or LabCorp, aim to be in the normal range as listed. Avoid RBC folate unless you also corroborate it with plasma or serum.
3) Plasma methionine, glycine, and sarcosine. Available on a LapCorp amino acids profile, a Quest amino acids profile, a Genova ION panel, or a NutrEval, methionine and glycine should be toward the middle of the range rather than the bottom and sarcosine is best being as low as you can get it.
4) The HDRI methylation panel. Aim to keep 5-CH3-THF in the normal range. If it is specifically low while other folate forms are normal, this suggests your MTHFR mutation is impacting your methylation pathway negatively. The “extended” panel has methionine and homocysteine, but not glycine or sarcosine.
5) Other tests of interest. Serum creatine from Quest or LabCorp might be a good way of testing whether your MTHFR mutation is affecting your creatine synthesis if you are not supplementing. Aim to be in the normal range. The combination of creatine, creatinine, and guanidinoacetate (the direct precursor to creatine) from the same urine sample can be used to test problems with creatine synthesis. Unfortunately, these are only offered from labs looking for a genetic disorder, such as Mayo Clinic, Greenwood Genetics Center, and Baylor Genetics, and I’m not sure if they are easy to order for someone with no suspicion of a metabolic disorder or whether the reference ranges would be relevant for looking at the impact of an MTHFR mutation.
Want to learn more? Listen to the podcast! Mastering Nutrition Episode 46: Living With MTHFR” (2A)
- Chris Masterjohn, Ph.D, newsletter
- Chris Masterjohn, Ph.D. articles/podcasts
- Podcast: Mastering Nutrition Episode 46: Living With MTHFR
- StrateGene (original link is broken, from Dr Ben Lynch’s website; try this: https://go.strategene.org/genetic-analysis/)
- Optimum Nutrition Micronized Creatine Powder Links to Amazon page for ASIN B002DYIZEO, for “Optimum Nutrition Micronized Creatine Monohydrate Powder “supplement
- Chris’s article: Meeting the Choline Requirement
- Micro Ingredients Sunflower Lecithin Links to Amazon page for ASIN B01N02YNF5, for “MicroIngredients: Sunflower Lecithin” supplement
- Study Abstract:Lecithin and Choline for Human Health and Disease Links to NCBI abstract for the article
- alpha-GPC Links to Amazon page for ASIN B00XWQSD7G, for Double Wood’s “Alpha-GPC” supplement
- Vital Proteins Marine Collagen Links to Amazon page for ASIN B0153YQH4K, for “Vital Proteins Marine Collagen” supplement powder
- Genetics Home Reference: ghr.nlm.nih.gov/gene/MTHFR
- Wellness Mama: wellnessmama.com/27148/mthfr-mutation/, including her quotes from Dr. Izabella Wentz and Dr Doni Wilson
- Dr. Axe: draxe.com/mthfr-mutation/