Tag Archives: methyltetrahydrofolate

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.



MTHFR mutation, or How to Know if You’re a Mutant.

So, everyone kind of freaks out when I use a word like mutant because it sounds so sci-fi and X-men-ish but the MTHFR mutation doesn’t give us anything nearly so exotic as superpowers, more like just more of the usual problems. The thing is, we’re all mutants in one form or another. We all have a tremendous degree of genetic variability that gives us the amazing and awesome diversity of looks, personalities, traits and oddities that make us human. These mutations, or genetic variances, can make our enzyme processes work differently; meaning more slowly, more quickly or not at all. This is why some people are still doing great after five cocktails and others are bleary-eyed and drooling.

MTHFR gene mutations. Here portrayed, wildly inaccurately, as mutant carrots.

Behold the mutant carrots. Muah hah ha… Don’t worry, MTHFR mutations aren’t quite this funky.  Thanks to simply-sharon.com for the great photo.

For the most part, genetic variance creates relatively small changes because there are so many overlapping systems in the body. It’s all part of the great mystery – our bodies are designed with a plan A, plan B, plan C and probably the back-up super-secret plan X just to make sure everything goes right.  There are, of course, a few places where no matter how many overlapping systems we have, our bodies can’t compensate for how many little things have gone wrong.

One of the places this can happen is in the various genes for a process called “Methylation.”  Methylation, as you might have deduced, is the process where your body adds a -methyl group to some other molecule to help it become more active.  One of the most important places this happens is in the gene that methylates folate (the B vitamin) into it’s active form.  This group of genes are called “methylenetetrahydrofolate reductase,” or MTHFR for short. If you have too many genetic variances in these genes then you may not be able to activate your folic acid or other B vitamins.

MTHFR Mutation Problems Include:

  • High homocysteine levels in your blood and urine – this increases your risk for heart disease including high blood pressure, heart attack and stroke.
  • Increased risk of neural tube defects and preeclampsia if you become pregnant.  Neural tube is your baby’s brain and spinal cord so it isn’t generally an area you want to be defective.
  • Improper neurotransmitter production – this can lead to depression, anxiety, mood disorders and complex psychiatric illness.
  • Increased risk for the eye disorder glaucoma.




So – none of these complications are good things.  Generally they’re not issues you want to be dealing with in your life and certainly not a combination of them (bad enough to be depressed, but to be depressed with heart disease sounds worse). This leads to two questions, which naturally I will endeavor to answer for you.

Who Should Test for MTHFR?

MTHFR has a lot of variability and different people notice it in different ways. Usually I suggest testing for people who have had anxiety or depression since childhood, for people who have parents, siblings, children or themselves with spinal cord defects that might be related, or for people who have anxiety, depression or mood disorders “in the family.” This being a genetic mutation we usually see it show up in parents, aunts and uncles, siblings and children so if many people in the family are struggling then it’s time to look at your genes. Also if your homocysteine tests high at your doctors office even if you’re taking B vitamins then there’s a good chance there’s a problem.

How Do I know If I’m a MTHFR Mutant?

Great question! The best way to know, is to test. Your doctor can run a complete genetic analysis which will give you all of this information and is by far the best option if you have insurance.  This would also mean you could get a prescription methylfolate to help your body compensate.  If you don’t have insurance then there’s a great not-too-expensive way to do it at home, which comes with the added bonus of learning just how much neanderthal you have in you (I’m 3%!!!).  It’s called 23 and Me, and it’s an at-home saliva DNA test kit that gives you all kinds of great information about yourself like your neanderthal percentage, your ancestry, and also more serious things like your disease risk, certain gene markers for serious disease and also genetic differences that may cause you to react differently to certain drugs or chemicals.  All in all it’s pretty nifty.

Once you get your DNA info from 23 and Me, then you can plug it into the neatest service ever, which is donation based, called Genetic Genie.  Genetic Genie can run a full methylation analysis (for a suggested donation of $10).  I can tell you from looking at mine that this gives you an overwhelming amount of info and lots and lots of great ways to compensate for any genetic oddities you might find.

What Do I Do if I Have A MTHFR Mutation?

The short version is don’t worry, and take a methylated B vitamin.  This means the folic acid should be methyl-folate or some variation thereof, including L-5-Methyltetradydrofolate, L-5-Methyltetrahydrofolinic Acid, or 6(S)-5-methyltetrahydrofolic acid (the longer the word, the better apparently).  The B12 should be Methylcobalamin, and you may see something extra in there to just add extra methyl groups like trimethylglycine or betaine anhydrous.  Also, you should NOT take regular folic acid or anything that isn’t a methylated folate, simply because all of those will compete with the methylated folates and just continue the problem.  It isn’t always this simple because there are additional mutations that can interfere as well so some people have side effects when they take methylfolate, which you can read about here. If you find out you have an MTHFR mutation it’s not the end of the world, there is plenty we can do. It’s a good idea to check your kiddos too, or just switch them over to the methyl forms of B vitamins, and also if you have other genetic relatives who are struggling to pass on the good word about methylated B vitamins and your own new super-mutant status.