Tag Archives: MTHFR and depression

Methylfolate Makes Depression WORSE! How Is This Possible?

Finding out you have an MTHFR mutation can be exciting, in it’s own strange way, because all of a sudden there is hope that you can actually help yourself and fix how you’re feeling, so it really feels like being kicked in the gut if you start taking 5-LMTHF and the methylfolate makes depression worse.  Have no fear, there is an explanation and also some possible solutions. Read on my friends.

Methylfolate makes depression worse! Don't worry - there is a solution. Great photo by © Philippe Ramakers | Dreamstime Stock Photos

Methylfolate makes depression worse! Don’t worry – there is a solution. Great photo by © Philippe Ramakers | Dreamstime Stock Photos

Why Does Methylfolate Make Depression Worse?

We recently talked about the terms “undermethylated” vs. “overmethylated” and although there aren’t great lab tests to show your status, typically you can determine your general tendency through their symptom picture.  Depression, however, can be ambiguous because it can happen in people who are undermethylated, overmethylated or people with totally normal methylation.  Although having the MTHFR mutation pushes many people into the undermethylated category, having the mutation itself isn’t enough to tell you if you’re under, over or normal. I myself am a compound heterozygous MTHFR mutant, but happen to have other genetic factors that make me an overmethylator – go figure.




5-L methyltetrahydrofolate (5-LMTHF) is suggested for everyone with a methylation issue – over or undermethylators.  It’s the first line of defence because it can actually help both groups to balance their methylation in different ways.  Also for depression specifically, folic acid or 5-LMTHF supplementation can be extremely helpful even without a known methylation issue because folate deficiency is a common cause of depression – so really for most people folate is beneficial. There is one group, however, who doesn’t respond well at all that that is undermethylated people with depression.

Let me clarify – anyone starting 5-LMTHF for the first time, or even increasing a dose, may notice some side effects for the first few days.  Starting to methylate differently can be messy and so this first few days isn’t enough time to know if you actually have a bad reaction. This is why we talk so much about starting with a low dose and easing your way up. If you’ve started with a low dose and you’re easing into it, but your depression gets worse and stays worse beyond the first week or so, then chances are you have undermethylated depression. This means methylfolate, folic acid and even folate rich foods are probably always going to make your depression worse.    Here’s why:

The link between Methylfolate and Serotonin

This is complicated because typically boosting your methylation cycle also helps your body to make more neurotransmitters via BH4 (we don’t need to go into it, but if you want a refresher you can read about it here). So 5-LMTHF is supposed to fix depression by boosting levels of serotonin, dopamine and other key neurotransmitters.  The problem is that 5-LMTHF, folic acid and folate all have a second effect on neurotransmitters, which is to depress serotonin through an epigenetic mechanism.

Epigenetics is essentially the study of how external factors (like nutrition, stress, oxidative damage, etc…) influence the way our genes express themselves. Folate and folic acid, according to the Walsh Research Institute, have an epigenetic effect on the SERT transporter.  The SERT transporter helps to reuptake serotonin after it’s been released. SERT is the target for many pharmaceutical antidepressants (SSRIs, or Selective Serotonin Reuptake Inhibitors). SSRIs work because they interfere with SERT and so serotonin stays active longer, which means you get more benefit from this happy neurotransmitter. Methylfoate, folate from foods and folic acid, while they increases serotonin production through BH4, also increase SERT via an epigenetic effect.  This means they help your brain to clear out serotonin faster, thereby reducing the amount of serotonin that is available for you to use. Essentially this makes folate the anti-anti-depressant.  Sigh.

As a brief reality check – Walsh Research Institute is convinced this is happening (see the link to their presentation above), many MTHFR websites are convinced this is happening, and it certainly explains a lot of what I’ve seen clinically, but for whatever reason I can’t find any published research that says definitively that this is happening so please take this with a grain of salt.

Methylfolate Makes Depression Worse For Me – Now What?

Don’t worry – you have a couple of options.  If you’re sure this isn’t just your body adjusting to methylfolate (the symptoms last beyond the first week of moderate supplementation) then it’s time to check to see if you fit the profile of an undermethylator. If that sounds like you, and your depression is getting worse, then let’s look at your choices.

  • SAMe – Ultimately the end product of the entire methylation cycle is SAMe, so it can be a helpful work around for people who can’t take 5-LMTHF.  This is where all that methylfolate is going and although it doesn’t entirely cover the necessity for methylated folate, it does help with the depression. This is partly because SAMe is a very slow acting serotonin reuptake inhibitor – just like the pharmaceutical drugs only much less powerful. As with any methylation issue, start with a low dose and work your way up.
  • Methionine – This amino acid is a direct precursor to SAMe in the body, and uses the MATI/II enzyme (coded by the gene of the same name) to go through the conversion.  Because this turns into SAMe it can be a much more cost effective way to get the same benefits, which again is as a slow acting serotonin reuptake inhibitor.  The only situation in which that isn’t going to be helpful is if your MATI/II gene has an issue or something is interfering.  Most people find methionine to be effective though, so this can be a far less expensive solution. Again, start with a lower dose and work your way up.
  • St. John’s Wart – This has nothing to do with methylation, only with serotonin.  Happily, St. John’s wart shows similar effectiveness to SSRI medications for major depressive disorder, with significantly fewer adverse events.  Here’s the research study, from the Annals of Family Medicine that compares St John’s Wart (referred to by it’s latin name, hypericum) with SSRIs and other anti depressant medications as well as placebo. Go nature!

It should be said that while SAMe and Methionine will help to augment the methylation cycle, they still aren’t providing folate of any kind, so they won’t protect against the more folate dependent issues like neural tube defects in babies and issues with pregnancy and fertility.  If you have undermethylated depression and are considering getting pregnant it is vital to work closely with a doctor who can help you to get the folate that you need and also help you to offset the depressive symptoms that might come with that. Even though methylfolate makes depression worse,  in pregnancy it might still be necessary so please consult a physician.



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.



MTHFR Basics Podcast

This week I had the lovely opportunity to be on Blog Talk Radio with Erin Chamerlik, The Real Food Revivalist- see getbetterwellness.com. Her listeners wanted to know a little bit more about MTHFR mutation.  You can listen to the recording here:

MTHFR Basics Podcast with Dr. Amy Neuzil, ND on The Real Food Revivalist Show

Tune in now to listen to this MTHFR basics podcast.

Tune in now to listen to this MTHFR basics podcast.

Listen for answers to questions like:

  • What is the MTHFR mutation?
  • Is it Common?
  • What are the implications for fertility and mood?
  • What sort of testing is available for MTHFR?
  • How do you start supplementing with 5-LMTHF?
  • Doesn’t this have to do with detoxification too?

 



I hope you enjoy this free podcast and if you have any questions for me please feel free to post them as comments. 🙂