Fertility & Preconception

Does Methylfolate Cause Anxiety?

by Nikki Warren on Aug 02, 2022

Does Methylfolate Cause Anxiety?

Well, it depends. Each individual is unique. I will address some of the issues here which might make a person more susceptible to anxiety from methylfolate. Methlyfolate is also known as 5-Methyltetrahydrofolate (5-MTHF).



Bill Walsh observed overmethylation when conducting his own studies. This concept has not yet been proven by science. Symptoms include anxiety, insomnia and a lack of motivation. You can learn more about this condition by hearing Bill Walsh speak about it in this YouTube video.

Treatment by Naturopaths for overmethylation is simple. You can take a high dose of vitamin B3, otherwise known as nicotinamide. A dose of 250mg daily is usually sufficient but your naturopath or nutritionist can guide you on this one.


Taking a high dose of 5-MTHF

In my clinic, I observed that some people were more prone to anxiety if they took more than 1000mcg of 5-MTHF. Luckily in Australia, it is illegal to have more than 500mcg of folate in a listed medicine (supplement).

You may read the AUST L number on the packaging. This will give you more information. So you can be sure what amount of folate is in the supplement.

Australia has on of the most tightly regulated supplement market in the world, making it a great option for purchasing supplements. Compared to the U.S., Australia is often the better choice.


Taking 5-MTHF at the same time as methylcobalamin

Methylcobalamin is the methylated form of vitamin B12. I have observed an issue in my clinic. I noticed that some people who take 5-MTHF and methylcobalamin for extended periods of time, can become over-methylated and anxious.

In fact, this is exactly what happened to me about 7 years ago. I purchased a protein powder that contained vitamins and minerals from the U.S. (from a reputable brand). This was back in the days when methylation was very rarely discussed in the nutritional world.

I knew that 5-MTHF was far superior to folic acid in terms of quality. However, I didn’t know at the time that a 5mg daily dose alongside 1mg of methylcobalamin was a ridiculous amount to take of the methylated forms of folate and vitamin B12.

I became anxious and my insomnia was out of control. After struggling with this for months, I started taking a high dose of vitamin B3 to address an unrelated issue.

Almost overnight my insomnia disappeared, and I no longer felt anxious. I understand how it feels when someone has the symptoms of over-methylation. Fortunately, I now know how to treat it from experiencing over-methylation myself.

This is why I chose to use hydroxocobalamin, the form of vitamin B12 found in food in the NaturoBest range.

You may need to consider avoiding l-methionine if you are over-methylated. Do not take l-methionine at the same time as 5-MTHF and methyl-cobalamin.

Your naturopath may prescribe Preconception Multi for Men if you are diagnosed with over-methylation. This preconception multi contains folinic acid and hydroxocobalamin, instead of the methylated forms of folate and B12.


Will a person become anxious on 500mcg of methylfolate?

My professional opinion is that people with normal methylation are unlikely to experience anxiety if they take 500mcg of 5-MTHF daily. Which is the dose found in NaturoBest Prenatal Trimester One. That is, of course, providing they are not taking a high dose of methylcobalamin or l-methionine at the same time.

If we are looking at methylation logically, do people feel anxious after eating too many green leafy vegetables? It is unlikely unless you are taking high doses.

What are the benefits of taking 5-MTHF?

In the majority of cases, it is beneficial to take folate as 5-MTHF. After all, active folate is the type of folate found in food such as broccoli.

  • Quatrefolic® is absorbed immediately as it is already activated. This means there is no risk of unmetabolised folic acid syndrome compared to non-methylated folic acid.
  • If you tend to be an under methylator you will definitely need 5-MTHF as the optimal form of folate.
  • If you have high homocysteine levels, this becomes a risk factor for miscarriage. Seeing as Quatrefolic® has immediate absorption it is obvious why Quatrefolic® is superior to folic acid in reducing homocysteine levels. This is especially important for people who are homozygous for the genetic mutation of C677T.


Quatrefolic® is a superior form of folate compared to other supplemental forms of folate such as folic acid. Genetic factors can affect methylation within the body. It is important to consider these when selecting the right form of folate.

It is important to know that you can test for genetic mutations that affect the MTHFR enzyme through your healthcare provider. If genetic testing is too hard to do or not accessible. You are better off to take methylated folate to be safer. We advise that you discuss this with your healthcare provider.

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