UPDATE: To see my evolution of understanding of 5MTHF and the methylation cycle, please watch the video of my presentation at AHS14.
This weekend at a continuing education seminar one of the topics covered was something called 5-MTHF. Never heard of it? No idea what it is? Join the club, most doctors have no idea what it is or why it’s important.
In this article, I’m going to change that for you.
Let’s start with a couple of definitions
Folic acid – what most people have heard of. Folic acid is actually an artificial B vitamin created and then added to foods like baked goods and also available in most multi-vitamins
Folates – these are naturally occurring in foods and have a few different forms which is why we call them folates and not just folate.
Here’s the trick
Folate, while it’s an important and essential vitamin by itself is useless to the body. It has to be converted through a series of steps to the active, useable form of folate called 5-MTHF (if you’re wondering that stands for 5-methyltetrahydrofolate). This is the form of folate that actually does the job of “folate”.
An analogy is gas in your car. While your car needs gas to work, you could fill it to overflowing with gas and without the engine to transform the gas into usable energy nothing happens.
What does 5-MTHF do?
5-MTHF is a critically important co-factor in a variety of essential reactions (that means it’s necessary for those reactions to work).
In case you’re curious, 5-MTHF helps recycle another cofactor called BH4 (or tetrahydrobiopterin) which is directly involved in the production of serotonin, dopamine, norepinephrine, epinephrine, and nitric oxide.
So, for you non-biochem geeks, here’s the takeaway, without sufficient 5-MTHF you can’t make your neurotransmitters, which means…
Anyone with psychiatric issues (depression, bipolar, schizophrenia and many more) or neurologic issues (including autism, ADD / ADHD, and many more) should consider looking into 5-MTHF.
What’s the issue?
Folic acid / folate is not usable by the body until it is converted into 5-MTHF. And here’s the rub, according to studies, in US Caucasians, around 50% are heterozygous for the MTHFR (enzyme that makes 5-MTHF) mutations, and about 10% are homozygous for MTHFR. In case you don’t remember your biology, we have two sets of genes (one from mom, one from dad). In this case, if you have a mutation in one you are called heterozygous, if you have a mutation in both you are called homozygous.
It’s even worse in Mexicans with up to 35% being homozygous, and about 25% being heterozygous for the mutation.
If you are heterozygous for the mutation your 5-MTHFR enzyme does not work as well, meaning you produce less 5-MTHF, if you are homozygous your enzyme works very poorly meaning you make MUCH less 5-MTHF.
Because this is a genetic issue you will often see these issues running strongly in families.
For example if you’ve been battling with depression your whole life and your siblings or parents or grandparents also have issue with depression or other psychiatric or neurologic issues, there’s a good chance there may be issues with 5-MTHFR.
On a side note, we talked about how it’s important for the normal development of a baby. If you or someone you know has had miscarriages, one of the reasons may be mutations in 5-MTHFR. Please get them tested and/or supplement with 5-MTHF. It can make all the difference in the world.
What you can do?
A genetic test is available, and any doctor can order it. It may or may not be covered by insurance, you should check your policy and see if they cover genetic testing. The test costs around $250. The good news is, since it’s genetic it only needs to be done once in your life. If you have issues with 5-MTHFR you have issues.
UPDATE: 23andme.com offers cheap genetic analysis. And while the service itself won’t tell you if you have MTHFR problems, you can download your ‘raw’ data from the service and then input it into other analysis programs – Stratagene is one service I like (no affiliation) – which can tell you if you MTHFR mutations. Be aware, 23andme collects your data, and therefore there are concerns with the privacy of your information.
If you get testing done and it shows an issue, or if you decide to just give 5-MTHF a try, you won’t be able to get it in ‘normal’ multi-vitamins or at a place like CostCo or regular pharmacies. 5-MTHF is a specialty vitamin that only high end supplement companies are using so you’ll need to look for it specifically.
There is also a form any doctor can prescribe called Deplin, which IF your insurance covers it, is very affordable, and if they don’t is way more expensive. It also has artificial colors and binders like most pharmaceuticals which may not work for some people.
I have not seen studies identifying 5-MTHF in any foods. My thoughts are that animal foods MAY have some 5MTHF in them (as animals have to convert folate to 5MTHF as well), so animal foods, especially organs are likely to be the only food source of 5MTHF. Since I can’t accurately suggest how much of a particular food might be needed to reach a certain level of 5MTHF if you have MTHFR issues or want to experiment with 5MTHF I recommend supplementation.
If after a couple of months of taking it daily, you don’t notice any benefit, stop. If you don’t see any change than 5-MTHF is not for you. And that’s okay.
I know of no serious safety issues with 5-MTHF, and the doctor lecturing on it, after having used it in over 4000 patients, has had two react negatively. One patient got more depressed each time they took it, and so just stopped taking it. Another had their seizures worsen after taking it, after stopping, their seizures went back to normal. So, very safe.
UPDATE: After having used quite a lot of 5-MTHF I still feel it is very safe for most people. In a minority of people I have seen it worsen moods, causing anger, worsening anxiety or depression, etc. These symptoms are short-lived and will fade when the 5-MTHF is stopped. These kind of symptoms in response to 5-MTHF indicate more significant methylation issues beyond just MTHFR. And obviously if you have severe mental health concerns, please proceed with caution and the help of an experienced health practitioner.
And some of the things this doctor had seen:
Takeaway: 5-MTHF is necessary to make all your neurotransmitters. If you have any issues with your mood or behavior, or with your nervous system, ask your doctor to test for 5-MTHF mutations.
UPDATE: Is 5-MTHF really magic? Well, for some people, yes.
In the years since learning about 5-MTHF and having used it in loads of people, I’ve seen it make huge changes for some people in issues ranging from anxiety to depression to autism to just plain “feeling happier and better”.
I’ve also seen it fail to make a difference for other people, so it’s not a panacea, even to people with confirmed MTHFR mutations.
Still it is extremely safe, and fairly inexpensive, so for most people who suspect it’s an issue, it’s going to be worthwhile to try.
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