The MTHFR A1298C mutation affects the enzyme methylenetetrahydrofolate reductase by inhibiting the utilization of 5-methyltetrahydrofolate (5-MTHF), or methylfolate, in producing an important chemical called tetrahydrobiopterin, or BH4. BH4 is a cofactor in neurotransmitter production, including serotonin, dopamine, melatonin, epinephrine, and norepinephrine. It also plays a role in the production of nitric oxide. If you have the MTHFR A1298C mutation, you may be deficient in BH4, which may cause psychological or neurological problems, as well as cardiovascular disease.

Genetic Testing

You can easily find out if you have the MTHFR A1298C mutation by ordering a DNA test kit from
23andMe ($99). Once you receive your results, go to Genetic Genie for methylation analysis (free). If your results show you have the A1298C mutation, you should consider supplementing with methylfolate and methylcobalamin.


Methylfolate supplementation can help address the MTHFR A1298C mutation by pushing the production of BH4, thereby preventing or reversing a BH4 deficiency.

It is wise to start with a lower dose (1 mg or less) and increase the dose after a few days. Many people only need to take 1 mg per day to see the most benefit, while others may need to take up to 10-20 mg per day. In any case, start low and increase gradually to avoid any negative side effects while your body adjusts.

There are many different forms of methylfolate, and some are better than others. Look for supplements that contain either Metafolin or Extrafolate-S, which have twice the bioavailability of generic forms. These products contain either Metafolin or Extrafolate-S:

Solgar Folate (as Metafolin), 800 mcg

Thorne Research 5-MTHF (as Extrafolate-S), 1 mg

Thorne Research 5-MTHF(as Extrafolate-S), 5 mg


Anyone taking methylfolate should also consider taking methylcobalamin, or methyl-B12, supplements, as B12 works synergistically with methylfolate.

Again, it is best to start with a lower dose and work your way up. Most people with the MTHFR A1298C mutation do well with 1,000 mcg methylcobalamin once or twice daily. If you also have the
C677T mutation, you may do better with 5,000 mcg doses.

All methylcobalamin products contain the same active ingredient, making them all reasonable options. However, you should pay attention to the other ingredients on the label, as many contain artificial flavors, dyes, or sweeteners. Jarrow Formulas methylcobalamin is a good option, as it contains only natural flavors, no added coloring, and is sweetened with xylitol. Xylitol is a natural sweetener that has an added benefit of promoting dental health by killing harmful bacteria in the mouth. Here are two options from Jarrow:

Jarrow Formulas Methyl B-12, 1,000 mcg

Jarrow Formulas Methyl B-12, 5,000 mcg


If you have the MTHFR A1298C mutation, you should consider methylfolate and methylcobalamin supplements to promote optimal levels of BH4 in your body.

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Disclaimer: The information on this site is not intended to be used in place of professional medical advice or treatment, nor is it intended to diagnose, treat, or prevent any disease. Always seek the advice of your physician or other qualified healthcare provider before taking any supplements.