While faulty methylation is linked to a host of health issues, it can be easily missed in conventional medicine.
5-methyltetrahydrofolate (5-MTHF) is the methylated form of folate, one of several B vitamins (B9). Both folate and folic acid—its synthetic form—are essential for healthy conception, fetal development, prevention of neural tube defects, DNA formation, cell growth, and other vital bodily functions.*
For women who are pregnant, breastfeeding, or looking to conceive, B9 supplementation might be worth discussing with your integrative provider. It may also be helpful for people undergoing high levels of stress or for those hoping to maintain normal inflammatory pathways.*
However, supplementing with folate or folic acid isn’t always enough, as it circles back to whether or not you are properly methylting. That is where 5-MTHF comes in. To understand the importance of 5-MTHF, you also need to understand a specific type of gene and its common variations.
Methylenetetrahydrofolate reductase (MTHFR) is an enzyme that works as a catalyst for various biochemical reactions, including the conversion of folate into 5-MTHF. The MTHFR gene itself is like an instructional manual for the production of the MTHFR enzyme, regulating methylation and causing the body to either over- or under-methylate.
Research shows that many people have one of several MTHFR gene variations, referred to as SNPs, or single nucleotide polymorphisms. You can think of each SNP as a variation of DNA building block. Some have no negative impact on health, while others can potentially impair a gene’s function.1
Foods—especially leafy green vegetables—come with naturally methylated folate. When food manufacturers began adding synthetic B9 (folic acid) to foods like white flour to ward off spina bifida in children, it was noted that several serious health issues began occurring. We now know that a significant chunk of the population (upwards of 30%) has trouble converting folic acid to folate, leading to low levels of 5-MTHF. This insufficiency can be due to poor liver function, gut issues, or a MTHFR gene variation.
Genetic testing has become widely available to evaluate potential gene variations, followed by metabolic testing and an organic acid panel for signs that the body is not methylating properly.
Besides considering supplementation, key steps in addressing this concern include eating plenty of foods naturally rich in methylated folic acid (L-methylfolate) and avoiding white flour and sugars.
Supplementing with this methylated form of B9 addresses an inability to methylate folic acid properly. It enables the conversion of homocysteine to methionine and the production of serotonin and melatonin. If you don’t fall into the category of people with a gene variation discussed above, 5-MTHF won’t be harmful, but it likely isn’t necessary.
It’s also essential to keep in mind that while most people can benefit from 5-MTHF supplementation, a small percentage of people with a gene variation that compromises methylation, or any other issue that hinders proper methylation, might actually experience worsening of symptoms.
Supplementing with 5-MTHF or any other methylated vitamin has the potential to increase anxiousness, irritability, anger, and other signs uncharacteristic to an individual. While uncommon, this is usually a sign of a downstream weakness in the methylation pathways, and a reminder of why it’s crucial to work with a doctor on your unique supplementation regimen.
The benefits of 5-MTHF can be profound if you have these specific gene mutations, although you might not feel or see changes.
For example, certain variations in the MTHFR gene can be severe in men and increase their risk of heart problems.2 Therefore, improved heart health, balanced iron levels, and overall lowered risk of future health issues are some unseen benefits.* You might also notice increased energy, or lustrous hair, nails, and skin.*
5-MTHF is especially vital for the developing fetus and allows the brain and spinal cord to develop rapidly and efficiently.* Women with low 5-MTHF levels during the conception and pregnancy phases have been shown to birth children with higher risk for behavioral or attention problems, GI issues, and further complications.3
Methylated folic acid is undoubtedly more costly than the less expensive—and potentially dangerous—folic acid, but it’s not the only way to support healthy levels of 5-MTHF.
The foods highest in L-methylfolate are dark green leafy vegetables, such as spinach, kale, dandelion greens, romaine lettuce, turnip greens, parsley, and Swiss chard. Other good food sources include sprouted legumes, cauliflower, broccoli, asparagus, cabbage, berries, oranges, grapefruits, and fermented foods such as raw sauerkraut, kimchi, and kefir.
These foods can help maintain healthy levels, but supplementation might be necessary for those with gene variations or other reasons for compromised methylation. Other methods to support methylation include reducing your exposure to toxins, limiting alcohol and tobacco, supporting gut health, and eating plenty of foods high in antioxidants, zinc, and magnesium to encourage normal homocysteine levels.
Ensuring adequate methylated forms of folic acid in one way or another is crucial.
MTHFR mutations are relatively common, so genetic testing is encouraged to gain insight not only on these variations, but other downstream mutations that might be compromising methylation as well. Whether you test or not, focus on a diet high in methylfolate-rich foods, and speak with your doctor about supplementing with 5-MTHF.
[1] https://rarediseases.info.nih.gov/diseases/10953/mthfr-gene-mutation
[2] Paul B, Whiting MJ, De Pasquale CG, Mangoni AA. Acute effects of 5-methyltetrahydrofolate on endothelial function and asymmetric dimethylarginine in patients with chronic heart failure. Nutr Metab Cardiovasc Dis. 2010 Jun;20(5):341-9. doi: 10.1016/j.numecd.2009.04.008. Epub 2009 Sep 12. PMID: 19748251.
[3] Bailey, S.W., Ayling, J.E. The pharmacokinetic advantage of 5-methyltetrahydrofolate for minimization of the risk for birth defects. Sci Rep 8, 4096 (2018). https://doi.org/10.1038/s41598-018-22191-2