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In Part 1 of this article, we talked about MTHFR polymorphisms and methylation. We also gave a short history of how we started adding folic acid to prenatal vitamins and the food supply. In Part 2, we’ll cover MTHFR-associated conditions. We’ll also give you some strategies for improving methylation through diet and supplementation. Don’t guess — test!

What Conditions Have Methylation Connections?

Those with methylenetetrahydrofolate reductase (MTHFR) deficiency are at increased risk for several diseases and conditions. These especially fall into cardiovascular, mental health, and immune-related health conditions.

Cardiovascular Conditions

High homocysteine levels are a known risk factor for heart disease. Some cardiovascular conditions that are associated with methylation issues are:

  • Blood Clots – Excess homocysteine due to poor methylation can lead to venous thrombosis. Venous thrombosis is a blockage in the blood vessels caused by a blood clot.
  • Vascular disease, including stroke – MTHFR mutations may lead to high homocysteine levels and damage to the vascular endothelial tissue. One study even found that two copies of the C677T mutation had a 3x increased risk for premature cardiovascular disease.
  • Coronary artery disease – Reduced MTHFR activity is also considered a risk factor for coronary artery disease, according to this study.

Mental Health Conditions

  • DepressionFolate deficiency is common in depressed people. Those with low blood levels of folate tend not to respond well to SSRIs and other antidepressant drugs. Supplementing with folate improves the results in these individuals.
  • Alzheimer’s A meta-analysis published in the International Journal of Neuroscience found that the C677T genotype was associated with Alzheimer’s disease in Asians but not Caucasians.
  • Schizophrenia Another meta-analysis published in Psychiatry Research found that schizophrenia patients had lower folate compared to healthy controls.
  • Obsessive-Compulsive Disorder Research published in the Indian Journal of Psychiatry in 2019 concluded that MTHFR polymorphisms are likely to play a role in early and late-onset OCD.

Immune Conditions

Researchers found connections between a low folate status and an overactive or underactive immune response, including cancer, in some studies.

The associations between taking folic acid supplements and increased cancer risk are more likely due to using the synthetic version. Remember that you are not doomed to get one of these conditions based on your MTHFR status. Knowing where you’re at helps guide you in taking care of yourself differently due to these SNPs.

How Can You Improve Your Methylation?

If you are one of the many people with a genetic variation like the C677T polymorphism, don’t worry! You can improve your ability to methylate and lower your susceptibility to chronic conditions.

Wellness Way Doctors Weigh In

Dr. Jesse Anderson of The Wellness Way Appleton says, “Don’t think of genes as ‘good’ or ‘bad’ Think of them as fast or slow. Knowing your genetics is important for knowing how to take care of yourself.”

Dr. Mitch of The Wellness Way Green Bay adds, “All genetic abnormalities or mutations are a moot point if you get rid of the inflammation.”

Again, genes load the gun, but the environment pulls the trigger. While trauma, toxins, and thoughts trigger dis-ease, what you start with matters. It’s always best to start with as much information as possible. That’s why we begin with proper testing.

Do Proper Testing

You won’t truly know if you have an MTHFR deficiency without testing. You may want to do a genomic test through a reputable lab, like Genova. Their Methylation Panel shows your MTHFR genetics. You may also be able to get an MTHFR test done through your medical provider and get it covered by insurance.

However, knowing whether you have a gene polymorphism is only the first step. You will also want to find out how that gene is expressing, and whether it is reducing enzyme activity. That’s where additional testing comes in. You can get your plasma homocysteine levels tested with a Cardiometabolic Panel. This test also gives other methylation markers, so you will know how well you are currently methylating. Wellness Way docs can get additional methylation indicators from the DUTCH Complete Hormone Panel.

Proper testing doesn’t stop at MTHFR or cardiometabolic testing. Wellness Way docs may also request food allergy, gut health, hormone, or other testing. These labs can all help identify which things are triggering poor methylation. A primary way they do that is by increasing your inflammation.

Reduce Inflammation

Genetics load the gun, but the environment pulls the trigger. In other words, your genes may set you up for certain deficiencies or toxicities, but your diet and lifestyle are what can make these genetic tendencies manifest. It’s been well-established by scientific research that inflammation is behind all chronic dis-eases.

How do you reduce inflammation? There are some universal ways, like lowering your stress and avoiding sugar. However, just like our fingerprints, each person is different. Again, food allergy testing and gut health testing can help identify immune triggers contributing to chronic inflammation.

Consume Foods with Methyl Donors

If you have a genetic difficulty in metabolizing folate, you’ll have to work a little harder to increase your folate levels by consuming methyl donors. The good news is that you can do a lot with your food choices. In fact, the word folate comes from foliage. After completing your food allergy testing, look over your non-reactive food list. There should be several options for green leafy vegetables and other methyl donors, like beets. Here’s a list of methyl donor foods:

  • Leafy greens: spinach, kale, collard greens, mustard greens, Bok choy, arugula
  • Broccoli, cauliflower, Brussels sprouts, asparagus
  • Beets and beet greens
  • Avocado
  • Chickpeas, lentils, pinto beans, white beans
  • Pumpkin seeds, sunflower seeds, sesame seeds
  • Brazil nuts and pistachios
  • Sardines, salmon, anchovies, tuna
  • Grass-fed beef, organic meats, liver, and other organ meats
  • Seaweed
  • Chicken eggs or duck eggs
  • Citrus: lemons, limes, oranges, and grapefruit
  • Banana, papaya, and goji berries

Foods are the best way to get your methyl donors as they have all the other nutrients needed to support absorption and usage.

Supplement with Methylated B Vitamins

Sometimes foods aren’t enough to get you to the next level. In that case, you can supplement. If you have an MTHFR genetic SNP, you’ll want to avoid synthetic folic acid and supplement with methyl folate instead. For cofactors B6 and B12, you will also want to seek out the methylated forms. In the case of B6, that means P5P over pyridoxine. In the case of B12, that means methyl-B12 (methylcobalamin) or hydroxy-B12 over cyanocobalamin.

  • The Wellness Way’s Wellness B Complex offers therapeutic levels of many of these B vitamins in their bioavailable (active) forms.
  • Methylcobalamin is the active form of B12, which is reliably absorbed and utilized by the body. This high-potency tablet with natural sweeteners supplies 5 mg (5,000 mcg) of B12. Tablets may be dissolved in the mouth or swallowed whole.
  • Our Active B12-Folate is a combination supplement featuring high doses of methyl folate and methyl-B12. Fast dissolving tablets allow for quick release into the bloodstream.
  • NEO40 has methylated folate and B12 with vitamin C and blood vessel-supporting nutrient nitric oxide (NO). Learn more about NEO40 here.

The Wellness Way Can Help!

Doctors and practitioners trained in The Wellness Way approach are well-versed in MTHFR. They understand the biochemical effects of MTHFR variations and how they affect the body. They also know how to bypass the genes and support methylation so your body can grow, repair, and detoxify at optimal levels. Dr. Jesse has had patients with one or both MTHFR mutations, yet they are methylating perfectly. He has had others who have optimal genetics for methylation, yet they are methylating poorly. We don’t guess –We test! Make an appointment with one of our Wellness Way practitioners today.


  1. Homocysteine and Hyperhomocysteinaemia – PubMed (
  2. Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease. – PMC (
  3. Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease. – PMC (
  4. The methylation, neurotransmitter, and antioxidant connections between folate and depression – PubMed (
  5. Association between the MTHFR gene and Alzheimer’s disease: a meta-analysis – PubMed (
  6. Lower folate levels in schizophrenia: A meta-analysis – PubMed (
  7. Roles of 5,10-methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in early- and late-onset obsessive-compulsive disorder – PubMed (
  8. Methylenetetrahydrofolate (MTHFR), the One-Carbon Cycle, and Cardiovascular Risks – PMC (
  9. Association of MTHFR C677T variant genotype with serum folate and Vit B12 in Iranian patients with colorectal cancer or adenomatous polyps | BMC Medical Genomics | Full Text (
  10. Gene-Environment Interactions in the Development of Complex Disease Phenotypes – PMC (


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