The MTHFR C677T mutation affects the enzyme methylenetetrahydrofolate reductase, which is the rate-limiting enzyme in the formation of 5-methyltetraydrofolate (5-MTHF), or methylfolate. If you have the C677T mutation, your ability to convert folic acid into methylfolate is significantly reduced. If you have a heterozygous mutation (+/-), you have about a 40% decrease in this conversion. If you have a homozygous mutation (+/+), your enzyme activity is reduced by about 70%.

It is important to avoid folic acid if you have the MTHFR C677T mutation (both heterozygous and homozygous), as you are more likely to be affected by the potential cancer-causing effects of excessive folic acid. Folic acid is only found in supplements and fortified or enriched foods; it does not occur naturally in foods. Folate found naturally in foods, such as leafy green vegetables, does not pose a problem.

The MTHFR C677T mutation may also cause high homocysteine levels, as methylfolate plays an important role in homocysteine metabolism. Elevated homocysteine levels can cause oxidative stress and increase your risk of heart disease.

Genetic Testing

You can easily find out if you have the MTHFR C677T 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 C677T mutation, you should consider supplementing with methylfolate and methylcobalamin.


The best way to address the MTHFR C677T mutation is with methylfolate supplements. This bypasses the MTHFR enzyme and ensures your body has enough methylfolate to detoxify homocysteine.

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. Your methylfolate requirements are also influenced by the
A1298C mutation. 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 with methylfolate in breaking down homocysteine.

Again, it is best to start with a lower dose and work your way up. Most people with the MTHFR C677T mutation do well with 1,000-5,000 mcg methylcobalamin once or twice daily. If you also have the
A1298C 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 C677T mutation, heterozygous or homozygous, avoid eating foods or taking supplements that contain folic acid. Instead, eat more leafy green vegetables and strongly consider taking methylfolate and methylcobalamin supplements.

Bookmark and Share

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.