Tag Archives: methylfolate side effect

The best dose of methylfolate for MTHFR mutants

MTHFR mutation is a huge factor in physical and mental health but we’re still learning the basics because it’s all very new research so the best dose of methylfolate for MTHFR mutants isn’t really a straight answer.  The good news is there are lots of ways to read your body and to learn the best dose of methylfolate for YOU. If you’re a little fuzzy on this whole MTHFR thing, then check out this post on the MTHFR basics.  This will give you a good framework for the whole conversation – also if you suspect you have the mutation, read more about how to know you’re a mutant here. If you, like me, already know that you’re a mutant then let’s tackle the hard problem of finding the best way to compensate for your body.  Finding the right dose of methylfolate can help to reduce anxiety and depression, stabilize mood, boost fertility, protect your heart and cardiovascular system and generally keep your body at peak performance so it’s important to take some time and do this the right way.

Finding the Best Dose of Methylfolate is a Process of Trial and Error

I wish there was just one answer – this is the right dose, but sadly it all comes down to what is the right dose for your body.  First off, I never suggest taking methylfolate by itself without any other B vitamins.  The B vitamins all have overlapping functions and so it’s important to have decent doses of all of them.  Typically though I start clients with a B complex that has a reasonably low dose of methylfolate – like maybe 400 mcg.  I really like the one from Pure Encapsulations called B Complex Plus. It’s basic, simple, and most people – even hard core mutants – tolerate it pretty well, but I’m not married to it. Any good multi-B with a low-dose methylfolate will do or you can look for a multivitamin that has methylfolate in it like Thorne Research Basic Nutrients.  Occasionally even this low dose creates a bad reaction – if that happens then we’ll have to start with a low dose MTHF by itself and split the capsule apart but this is the option of last resort. First, let’s try the low dose B complex or multivitamin and see what happens.




Keep in mind the first three days of any MTHF might be difficult and there may be some adjustments. You may  notice that you’re a little agitated, or anxious, or depressed or just feel a little spacy or off. With any luck that should pass pretty quickly and we’ll wait for things to stabilize before increasing the dose.

If the Low- MTHF  B Complex or Multi Works for You

Great! We’re on the right track.  Even if this is the right dose for you there might be a few odd adjustment days in the beginning – that is totally normal.  Just wait until everything settles down and see how you’re feeling.  Typically with this low dose people may notice a small spike in energy or a little boost to mood, but often it isn’t enough methylfolate to start to touch the issues – that’s okay because it’s enough to get the ball rolling.  The next step would be to add a 1 mg (1000 mcg) MTHF by itself to the B complex you’re already taking. We’re looking to make forward progress without rocking the boat too much.  Each time you increase the dose there may be another adjustment reaction as your body gets used to things, so try to stick it out for 3 days before you make a final judgement about it.

If the Low-MTHF B Complex or Multi DOESN’T Work for You

Then we switch to plan B.  Plan B is a little messier and more tedious, but it could make all the difference for how you’re feeling on a day-to-day basis.  Start with a 1mg MTHF – I prefer a capsule so that you can just open it and portion out the powder (instead of trying to cut or crush a tablet). In this situation start with 1/4 of the capsule – easiest is mixing it with some peanut butter, applesauce or yogurt and taking it that way.  It tastes pretty gross, but hopefully you can hide it in something. Again count on about 3 days of adjustment, but we’re starting with very low doses here so hopefully that will be fine and if it’s still too much then you can cut it down even further. Once you get to the dose you can tolerate, keep it there for a couple of weeks and try to slowly increase.  By now your body has started to process some of the back-log of work so it might be easier to tolerate a bigger dose. Now would be a great time to try going to the B complex with MTHF or multi with MTHF because you do still need all those other B vitamins.

What to Do If You Can’t Tolerate ANY MTHF?

Yup – I’ve seen clients like this. They take the tiniest amount and spiral into depression or anxiety attacks or start to feel itchy. Not fun at all!  In this situation it’s tiny-dose niacin to the rescue.  For whatever reason taking about 10-50 mg of niacin  – this is usually 1/10th or even less of a 500 mg niacin tablet.  It’s a tiny dose, but for many people it really helps to ease the transition into MTHF.  Start again with a small dose from the opened MTHF capsule (maybe 1/4) and add a tiny shaving off the niacin capsule and see how you do.  The niacin seems to buffer things a big so that the MTHF is a little bit easier to tolerate – again it’s about helping your body to do some of the work that has piled up in the absence of activated B vitamins. If niacin doesn’t help then sometimes hydroxycobalamin will.  This is a little bit mysterious because you’d think it would be methylcobalamin (the methylated form of B12 which MTHFR mutants also have a hard time making).  Oddly, the hydroxycobalamin form seems to be the most helpful when you’re starting MTHF dosing and when niacin doesn’t take the edge off, a lot of times hydroxycobalamin will.  Do you see what I mean about trial and error?




Methylation, it's complicated. The best dose of methylfolate is out there for you - you just have to find it. Thanks to flickr user Franklin Park Library for the image.

Methylation, it’s complicated. The best dose of methylfolate is out there for you – you just have to find it. Thanks to flickr user Franklin Park Library for the image.

How Do I Know I Found The BEST Dose of Methylfolate?

We are doing all of this to help you feel better as a whole human.  Methylating your B vitamins or taking methylfolate is supposed to help boost your energy, stabilize and elevate your mood, help your body with detox reactions and reduce a wide variety of symptoms over time.  So how do you know you’re’ at the perfect dose for you?  Well – you should feel better.  Keep in mind the prescription methylfolate comes in 7 mg and 15 mg doses (deplan).  Those are a whole lot bigger than the doses we’re starting with above so when you find a good starting dose for yourself then stay there for a couple of weeks.  If you’re feeling fine and stable but not a lot of improvement then try a higher dose and see how you feel with that. For everyone there is a sweet spot where they feel better and more energetic, but not anxious or wound up.  Keep in mind every time you increase dose those first 2-3 days may be a little bit odd.  Don’t judge by those days.

Things to Remember:

  • You need all the B vitamins, not just methylfolate so don’t leave those out of the mix. A good methylated multi or methylated B complex is a great foundation to start with.
  • Methylation affects neurotransmitter formation, inflammation and detoxification so lots of random symptoms can pop up when you increase the dose. Give it a few days before you make judgements.
  • Increasing doses slowly is easier for your body to tolerate than just dumping a high dose in all at once.
  • Tiny doses of niacin can help smooth out the transition.
  • Hydroxycobalamine, a form of B12, can also help to make taking MTHF a little easier.
  • Every body is different so the best dose of methylfolate for you could be completely different from the perfect dose for someone else.
  • Every MTHFR mutant has mutations in different spots and combinations plus a whole host of other genetics to deal with. Don’t get discouraged – there is always a perfect solution, you just have to find it. Generally though the more mutations you have the longer it might take to find the right balance.
  • Methyl donors like Trimethylglycine (TMG)  which is also called betaine anhydrous can also support this process by donating methyl groups for your newly-functioning methylation pathways to use.
  • Riboflavin-5-phosphate also supports methylation and homocysteine metabolism (which tends to build up if you’re not a great methylator) so sometimes a small dose of this will help things out as well. It should be in a good B complex.
  • It’s important to avoid sources of folic acid (which there are many – think all of the “enriched” grain products like cereals, breads, pasta) including multivitamins with folic acid or vitamin-enhanced foods. Plain old folic acid will compete with the methylfolate you’re taking and make it harder for those pathways to work.

Specialty Methylation Products

There are a few great methylation products out there that have a combo of supportive ingredients.  One of my favorite is Methyl-Guard Plus by Thorne Research, which combines a reasonably high dose methylfolate with methyl-B12, TMG and riboflavin-5-phosphate.  It can be a high dose to start with though, so especially if you have a few mutant genes it’s a good idea to start with the lower dose products and work your way up. There is no sense shocking your body. Too high a dose can cause as many problems as too low a dose so it’s important to find your sweet spot.

The bottom line is that this is no different from any other aspect of health. You need to find the right thing for YOUR body and there is no one size fits all.  The best dose of methylfolate for you is out there – you can find it.  I feel like the biggest thing is to ease your way into it and not over-flood your body. Start slow and work your way up – better to get there slowly than to give up because you felt so bad when you tried the high dose.



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.