Tag Archives: methylfolate depression

MTHFR and depression – what is the link here?

MTHFR mutation is becoming kind of the “in” thing to have at the moment and it seems like everyone talks about MTHFR and anxiety, MTHFR and heart disease, MTHFR and depression. The question is, why does a gene for the enzyme that activates folic acid have anything at all to do with those things?  First off, if this sounds like gibberish, then here’s some background reading on MTHFR and on MTHFR and folate. Now – lets see if we can decode the link between MTHFR and depression, because understanding this can hopefully help a lot of people who are struggling start to regain some normal and some happy in their lives.

What is the Link Between MTHFR and Depression?

At the simplest most basic level, your body needs methylated folate (which is what you don’t make very well if you have the MTHFR mutation) in order to manufacture the neurotransmitters serotonin, dopamine, epinephrine and norepinephrine and also the neurohormone melatonin (which helps with sleep among other things). The methylated folate isn’t used directly for these neurotransmitters, but it helps to make something called BH4, or tetrahydrobiopterin if you want to be technical about it. BH4 is then used to help the neurotransmitters building blocks (which are amino acids) to be converted to the active neurotransmitters that your body uses for brain cell signaling.

This is the link between MTHFR and depression, in not so plain english. Great diagram from Dr. Rostenberg, in this post which goes into the subject in more detail. Dr. R was kind enough to give me permission to use this! http://www.beyondmthfr.com/mthfr-depression-folate-bh4-connection/

This is the link between MTHFR and depression, in not so plain english. Great diagram from Dr. Rostenberg, in this post which goes into the subject in more detail. Dr. R was kind enough to give me permission to use this! http://www.beyondmthfr.com/mthfr-depression-folate-bh4-connection/




Um… Still Not Following.

Right – so I honestly don’t think it is hugely beneficial when you’re trying to fix MTHFR  issues in yourself to actually dive too deep into the biochemistry of what is happening because it gets overwhelming really quickly.  Suffice to say that your body has trouble making neurotransmitters if it can’t make BH4 because there just isn’t enough methylfolate. When your body has trouble making neurotransmitters, then you can start to see symptoms including these.

Symptoms of Low Serotonin (Think Negativity and Anxiety):

  • Negative thinking – Pessimistic, cynical or distrusting thoughts.
  • Craving for sweets and starches – Bring on the bread. With a side of fries. These foods temporarily boost serotonin levels in the brain, so you might reach for these more frequently
  • Sleep trouble – You need to make serotonin before you make melatonin (your primary sleep hormone) so this can be a big issue.
  • Low self esteem – Serotonin is one of the chemicals that helps you to feel good about you. Without it, you might feel socially anxious, inferior, or incapable.
  • Anxiety – worry, apprehension, obsessive thoughts and panic attacks are all more likely when your serotonin is low.
  • Aggression – Violence, aggression and suicidal thoughts or actions (violence against yourself) are all symptoms of low serotonin.
  • Impulsive behaviour – Low serotonin can reduce your ability to control impulses.

Symptoms of Low Dopamine (Think No Motivation and No Reward):

  • Lack of Motivation – No real “reason” to do things that matters to you. This also shows up in difficulty getting going in the morning and outright fatigue.
  • Joylessness – Dopamine helps you to actually feel the positive effects of enjoyable things. Without it, everything is a little blah. You have a hard time experiencing pleasure.
  • Memory Loss – Forgetfulness, lack of focus and outright memory loss.

Symptoms of Low Epinephrine and Norepinephrine In the Brain (Think Get Up and Go Got Up and Went)

  • Mentally Worn Out – Mental energy is lacking. All mental effort feels like far too much.
  • Inattention – Can’t really focus on anything.
  • Lack of Excitement – Yeah. Another day in paradise.

The short version of all of this is that without MTHFR you have trouble methylating folate. Without methylated folate, your body lacks Bh4. Without enough BH4, you have low levels of these neurotransmitters and with low levels of these neurotransmitters, everything feels pretty yucky. Like sad, apathetic, anxious, joyless yucky. Is there hope? Hell yes! This isn’t the post for it, but here’s some info about finding the right dose of methylfolate for you, and here’s one about foods that are high in natural sources of folate. It’s a great place to start. Even if you have depression but haven’t confirmed that you have a MTHFR mutation this can be a really great place to start.



Methylfolate Side Effects: MTHFR problems

We’ve talked about the MTHFR mutant problem before (right here) but haven’t really addressed the actual taking of methylfolate.  Folate sounds so benign, so harmless but sadly there can be methylfolate side effects. 5-MTHF fallout, if you will. We mutants are out there, walking among you unable to convert regular old folic acid into methylfolate, or 5-MTHF for short.  I will stand with pride among you my brothers and sisters because yes, I too am a mutant.  Deep shuddering sigh.  As it turns out, using gene markers alone to plan a healthy nutritional protocol is not as straightforward as it would seem.  The reason being that every system in the human body has a glorious level of redundancy – we are literally designed to fail in eight thousand ways and still function normally.




Simply having the MTHFR mutation doesn’t actually mean that high-dose methylfolate like Deplin® which is prescribed in either 7.5 mg or 15 mg doses is a good idea.  The reason for this is that your body has literally hundreds of overlapping systems that are involved in every function that is even remotely related to the ways you use folate in the body. These overlapping systems and layers of function help our body to function normally even with multiple mutations that may result in genuinely low levels of 5-MTHF. Obviously that’s awesome when you don’t have methylfolate, but it can be a little overwhelming when all of a sudden you have a ton of it.

methylfolate side effects can happen even with a great product like this 5-MTHF 5-MTHF – One of my favorite methylfolate supplements, but there can still be methylfolate side effects.

Picture flooding your system with methylfolate when there has been relatively little (and when your body has been functioning reasonably normally with relatively little). Your cup literally runneth over. In some cases, your body has been starving and so it’s a welcome relief like rain in the desert – all functions get better and you’re ridiculously glad to have some resources to work with.  In other cases the flood of 5-MTHF is literally a flood and you’re stuck trying to clean up the mess.

Methylfolate Side Effects:

  • Mood changes: depression, irritability, severe anxiety
  • Pain: sore muscles, joint aches, headaches, migraines
  • Physical Symptoms: rash, acne, heart palpitations, nausea, insomnia

You will notice that some of these side effects are exactly the symptoms we’re looking to fix by taking the methylfolate, which seems a little ironic and inconvenient.  Such is the way of medicine, no? Like the drug you take for constipation that may cause constipation.  Thankfully here the benefits far outweigh the risks, you just have to know how to do it right.  Remember that methylfolate is something your body actually needs, so it’s important to find a way to take it well.

Avoiding Methylfolate Side Effects:

    • Start slow:  Some people with the MTHFR mutation have no trouble taking methylfolate and feel a world of difference from it.  For the rest of us it’s a little too much, a little too quickly.  If that is you then backing the dose way down to what might be in a good multivitamin (400 – 800 mcg) is a great way to start.  From there you can slowly adjust your dose to find your own optimal dosage level.
    • Personalize: When we’re talking about your genes it really is all about YOU.  Just because something works for lots of people with the MTHFR mutation doesn’t mean it will work for you, so above all trust your body and your symptoms.  If you’re having a problem doing something one way (even though that way works for your doctor or your neighbor or everyone else on a forum) trust that and change your strategy.
    • Pulse Your Dose: For some people it helps to have some days on and some days off, meaning to take methylfolate at whatever dose your body can tolerate for some days but not others.  For my body personally the best strategy I’ve found so far is taking lower doses five days per week and taking weekends off (convenient too!) For some of my clients it’s a week on/week off plan at a higher dose.  This really does come down to experimenting with your body to find what is right for you.
    • Expect Some Adjustment: Remember that your body has been compensating for all of your mutations for as long as you’ve been alive so suddenly changing the entire playing field is bound to create a few waves.  Before you make a snap judgement about what works for you and what doesn’t give things a few days to calm down. Your body will constantly astound you with it’s flexibility, it’s adaptability and it’s ability to cope with ridiculously huge changes but even your miraculous body may take a couple of days.
    • Niacin to the rescue: 50 – 100 mg of time-release niacin can be incredibly helpful to counteract some of the side effects of methylfolate if an alternative dosing plan isn’t enough to make you feel awesome. Niacin helps your body to use excessive SAM (S-adenylmethionine) which can build up in some people taking methylfolate. It’s important to also experiment with your dosing to find the right level of niacin for you, and in larger doses niacin, even in it’s time-release form, can cause flushing.




  • Antiinflammatories: Some of the problem is just basically that your body was probably inflamed going into the methylfolate therapy and changing your protocol can stir everything up.  Also by taking 5-MTHF you are allowing your body to start to catch up on detoxification and repair, which can also increase your level of inflammation while everything is being sorted out. Good strong natural anti-inflammatories can help to decrease symptoms and help your body to adjust, especially while you’re finding your optimal dosage. A lipid-soluble form of curcumin (from turmeric) like Meriva® can make your life far easier.  Other great natural anti-inflammatories include fish oils, green tea, pycnogenol, boswellia, resveratrol and cat’s claw. Following an anti-inflammatory diet is tremendously helpful as well.
  • Hydroxycobalamin: In an odd twist this non-methylated form of vitamin B12 can help to control some of the side effects of 5-MTHF as well.  One of the benefits of taking methylfolate is that it increases your levels of nitric oxide, which is the signal that helps your blood vessels dilate.  Which is exactly why it helps with cardiovascular risk and headaches and lots of the other things it helps with.  Like with everything else in life, too much of a good thing is sometimes a really bad thing.  So if your nitric oxide levels end up becoming too high then your body starts to make free radicals, and those free radicals create side effects.  Hydroxycobalamin can help you to counter this effect. Again, experiment with your dosing.

Remember that if you have MTHFR mutations then your body will function better on so many levels by getting the methylfolate that you’ve literally been starving for, so it’s worth it to find the right dose and the right way of taking methylfolate for you.  This can save you from heart disease, stroke, heart attack, periodontal disease, anxiety, insomnia, depression, mood disorders, reproductive problems, even birth defects in your children. Just because you have methylfolate side effects doesn’t mean your body doesn’t need it, so keep trying to find the way that works for you.