Many of you know about methylation and how problems with this process are linked to heart disease, diabetes, Alzheimer’s, attention deficit hyperactivity disorder (ADHD), autoimmune disease, and autism. But did you know that methylation problems may also be involved in other more surprising areas of your health? In this article, we’ll dive into those other lesser-known consequences of faulty methylation and what you can do about it. But first, a refresher course on what methylation is and how the MTHFR mutation is involved in methylation problems.
What Is Methylation and MTHFR?
Methylation happens in every cell of our body. It acts like a switch that turns genes on and off. That means if you’re genetically predisposed to develop a disease, healthy methylation can stop you from developing that disease by blocking the expression of the disease-related gene. It’s involved in immunity, detoxification, cell renewal and energy production, neurotransmitter synthesis, and removing excess estrogens and histamine, to name just a few of its functions.
Methylenetetrahydrofolate reductase—MTHFR for short—is an enzyme involved in the methylation process. Its primary role is to convert folate or folic acid* into the active form (5-MTHF). When MTHFR is working properly, levels of an amino acid known as homocysteine stay balanced. However, many people have a variant (also called a polymorphism) in the MTHFR gene, which leads to poor functioning of the MTHFR enzyme. This also leads to high levels of homocysteine, which in turn make people more vulnerable to a number of diseases.
Variants of the MTHFR gene include C677T or A1298C. Depending upon whether you have one or two copies of the C677T variant, levels of the MTHFR enzyme activity can drop by 33% to 35% or 70% to 75% respectively. Two copies of the A1298C variant can cause MTHFR enzyme activity to fall by 39%. You can find out whether you have any of these variants by asking your doctor to order MTHFR testing.
*A word on nomenclature. Folate refers to the water-soluble B-vitamin that we find naturally in whole foods. Folates found naturally in food include 5-methyltetrahydrofolate (5-MTHF), 10-formyltetrahydrofolate, and 5-formyltetrahydrofolate. Folic acid refers to the synthesized, oxidized compound that was discovered in the 1940’s. It is what you find in dietary supplements and food fortification.
Lesser-Known Consequences of MTHFR Mutations
Even people who know about methylation may not realize that certain MTHFR problems are linked to the below listed diseases. If your patients have any of these conditions, it’s a good idea to order , which is available from Rupa Health as a blood specimen, buccal swab, or blood spot. That way you can address your patient’s methylation needs with a customized treatment plan.
Several studies have found a connection between open-angle glaucoma or central retinal vein occlusion and either high homocysteine levels or variants in MTHFR genes. In two of these studies, there was an association between primary open-angle glaucoma and the presence of the C677T variant. In one study, glaucoma was associated with high homocysteine levels although not the C677T variant. The MTHFR C677T mutation and high homocysteine levels also occur more frequently in patients with central retinal vein occlusion, a condition where small veins that carry blood away from the retina are blocked.
People with migraines may benefit from testing for MTHFR gene variants. A systematic review and meta-analysis of the medical literature included a total of 15 studies of people with migraines. There was a significant link between the MTHFR C677T polymorphism and migraine with aura. In non-Caucasians, the MTHFR C677T variant also was linked to total migraines.
High levels of homocysteine block healthy blood flow and lead to clotting disorders. Presence of the MTHFR variants C677T and A1298C are associated with high homocysteine levels and are linked to deep vein thrombosis and pulmonary embolism.
In case studies, there’s a relationship between weakened activity of the MTHFR enzyme and epilepsy. Patients with epilepsy also often have high homocysteine levels and the MTHFR C677T mutation.
The MTHFR variants may not be the first factor that comes to mind when investigating the cause of erectile dysfunction (ED). However, there’s evidence that high homocysteine levels and MTHFR polymorphisms may play an important role in the condition and may explain why ED medications may not work in some men. In one study, the C677T mutation, high homocysteine levels, and low folate levels were associated with ED and not responding to ED medications. When researchers gave folic acid to the men who were not responding to the ED medications, their erections improved.
The researchers concluded that “the C677T mutation may interfere with erection mechanisms and thus be responsible for ED.” What’s more, in cases of high homocysteine levels associated with low levels of folate, the administration of ED medications may fail if not preceded by the correction of levels of homocysteine and folates.
Scientists believe that MTHFR gene mutations could be to blame for infertility in hypothyroid patients. They think it’s worthwhile to screen for MTHFR gene polymorphisms in hypothyroid women and their partners who are unable to get pregnant if infertility continues even after normalizing thyroid function.
Two hypothyroid women with either a long history of infertility or repeated pregnancy loss served as an example of this strategy. Their problems with having a successful pregnancy occurred even after their thyroid function was normalized. They were only able to successfully carry a baby to full term when the MTHFR gene mutation was detected and they were given active folate (5-MTHF).
Ways To Support Healthy Methylation
Speaking of 5-MTHF, supplementing with this type of folate is one of the most effective ways to restore methylation in cases where methylation testing reveals the presence of the MTHFR gene variants. If MTHFR activity is weak, the body isn’t doing a good job converting folate to its active form. L-methylfolate (5-MTHF) supplements bypass the MTHFR enzyme to replenish levels of this critical methylation supplement.
Just be careful not to overdo it with the methyl donors. Too much folate, folic acid, or other methylation supplements can lead to hypermethylation, which can cause problems, too. Nearly all Americans have folic acid circulating in blood that they cannot properly break down, mostly due to folic acid vitamins on top of folic-acid-fortified foods. Therefore, the best strategy may be to test folate biomarkers and go slowly on the supplements while optimizing methylation through diet and multimodal interventions, as well as balancing other factors like the microbiome. Balancing the microbiome can in and of itself lead to higher folate levels.
Rupa Health helps practitioners take the guesswork out of the labwork experience. Clinicians can order, track, and get access to 20+ lab companies in one place, at no extra cost. Choose from a variety of laboratories that test for MTHFR, available as either whole blood (requiring a blood draw), buccal swab, or blood spot, including :
Access Medical Laboratories
Cell Science Systems
Take a look at our Live Classes for practitioners and our Functional Medicine Lab Testing articles.