Does Methylfolate Cause Anxiety?
Fertility & Preconception

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.  Otherwise known as 5-Methyltetrahydrofolate (5-MTHF).



Although this concept is not yet scientifically proven, overmethylation is a condition that was observed by Bill Walsh when conducting his own studies. 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.

Naturopathic treatment 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).  If you look for the AUST L number on the front of the packaging, you’ll know you’re in safe hands.  Yet another good reason to purchase a supplement from Australia rather than the U.S.  Australia has the most tightly regulated supplement market in the world.


Taking 5-MTHF at the same time as methylcobalamin

Another observation in my clinic was that if people took 5-MTHF at the same time as methylcobalamin, the methylated form of vitamin B12, over a long period of time, they could become overmethylated and anxious as a result.

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, what I didn’t know was that the 5mg daily dose alongside the 1mg 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, coincidentally 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…. relief. So when a person presents with the symptoms of overmethylation, I can certainly empathise and luckily I know exactly how to treat it.

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

Another supplement you should avoid if you are overmethylated, is the amino acid l-methionine (or avoid taking at the same time as 5-MTHF and methylcobalamin).

If your naturopath diagnoses you with overmethylation, they may prescribe Preconception Multi for Men as a preconception multi which contains folinic acid and hydroxocobalamin rather than the methylated forms of folate and B12.


Will a person become anxious on 500mcg of methylfolate?

In my professional opinion, it is unlikely that a person who is not overmethylated to begin with, will suffer from anxiety if they take a daily dose of 500mcg of 5-MTHF (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.

Let’s look at this logically.  When was the last time you felt anxious after eating too many green leafy vegetables?  As I say, it’s 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 (rather than having to go through several biochemical steps to metabolise into active folate, it already is active folate). This means there is no risk of unmetabolised folic acid syndrome. 
  • If you are undermethylated, you will most certainly need 5-MTHF.  
  • 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.  Especially in people who are homozygous for C677T.