I Have MTHFR, How Do I Start 5-LMTHF?

Once you’ve adjusted your diet, you have a new baseline. This is your new normal and it may be great, it may just be getting there (but not great yet). Make sure you give yourself about a month on your new diet — with MTHFR it’s way better to go slow and give your body time to adjust to things properly before you jump into something new. This is when you should start to think about supplementing.

Three rules to successfully start 5-LMTHF supplements:

  1. Always start low – use the lowest dose you can find. You can always add more, but once you’ve taken it, it’s hard to get it back out. Start with a low dose.
  2. Always go slow – give your body time to get used to the low dose before you increase. At least a week, but two if you know you’re particularly sensitive.  It is really common for someone to be able to take something for three days and then start to have symptoms because the dose is actually a bit too high and they’re pushing too hard.  Make changes slowly and be as willing to decrease the dose as you are to increase the dose. There is no right dose for everybody, only the right dose for you.
  3. Change only one thing at a time – I see it happen all the time that people get excited about a new health journey, add five supplements from internet research, then have some kind of symptom and have absolutely no idea where it came from or what is causing it, so they end up dropping all of those supplements.  This isn’t the best way forward. If you make small changes with only one supplement at a time, you can avoid this problem and you’ll always know exactly how you respond to something.  That doesn’t mean that adding another supplement might not change the dose you need of something else, but at least it helps you to know where to look.
Be like the snail when you start 5-LMTHF

Start 5-LMTHF:

If you’ve already:

  • Taken folic acid out of your diet
  • Added in natural folate
  • Started a multivitamin or B complex without folate or B12 

And you’re tolerating these changes well, then you’re at the point where you might consider adding some extra 5-LMTHF. 

Start with the lowest dose you can find and if you can only find high doses, cut them (if they’re tablets) or take the powder out of capsules and divide it. If you typically react strongly to things you take, which is common for in MTHFR issues, then start even lower than you think you need to.

The Three Possible Reactions to 5-LMTHF

  1. Miracle! – It starts out as a miracle (although it might feel weird the first couple of days because your body is adjusting), it keeps being a miracle and everyone is happy.
  2. Bait and switch – It starts out amazing and you love this thing. A couple of weeks later you find yourself either spackling minuscule cracks in your ceiling at midnight because you have too much energy and can’t sleep (overdose), or hating everything and everyone because you feel toxic (too much, too fast).
  3. 5-LMTHF is the devil – If it always feels bad, there is a good chance you will either never tolerate it, or only tolerate tiny doses later on in the process.

It is normal to feel a little strange for the first few days. Remember, 5-LMTHF is the only form of folate that bypasses the MTHFR enzyme and that means it can feel a bit odd the first time you take it. That enzyme has been dysfunctional, to some degree, your whole life and your body is going to need a minute to adjust. For me, the only way I could describe it was that my brain felt “different.” This is a useless description, I know, but there wasn’t really anything I could put my finger on, it was just … “different.”

5-LMTHF has the potential to change your neurotransmitters, your cellular energy, your antioxidant balance, and lots of other things very quickly, so it can feel a little odd. Your body has probably never experienced this before.

Outside of a normal adjustment reaction, it is also possible to have a bad reaction. The most common ones I see are anxiety or restlessness, edginess, depression, or difficulty sleeping. 

Remember, 5-LMTHF is the only form of folate that bypasses the MTHFR enzyme, and that means it can feel a bit odd the first time you take it.

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Any big uncomfortable symptom should be considered a bad reaction and if that happens, stop the 5-LMTHF and wait until the symptom clears before you try it again. If the symptom was really bad then try again at a much lower dose. Even if you can tolerate natural folate in food, you might not handle 5-LMTHF well. 

If you have an adjustment reaction, but it clears in a few days and you’re tolerating the dose of 5-LMTHF that you’re taking, that’s great news! Stay at this dose for a couple of weeks and then try increasing it by a little bit. Dosing is very individual with MTHFR and there isn’t any way to give you a target dose, but there is a right dose for you out there somewhere.  It’s just a matter of slowly working your way up until you find it. 

What If I Can’t Tolerate 5-LMTHF?

This is a surprisingly common issue. If you just can’t take any 5-LMTHF at all, try a tiny dose of folinic acid instead. Folinic acid is metabolized differently than 5-LMTHF, but it’s a natural form (like the natural folate in foods) and is often easier to tolerate for MTHFR folks, even though it still needs the MTHFR enzyme to be activated.  If you need a refresher on folinic acid or the different forms of folate, check out this post. Here is a diagram of the methylation cycle showing where the different types of folate come in.

Folinic acid still goes through the MTHFR enzyme, but it bypasses the DHFR (slow) enzyme and the DHFR (fast) enzymes. For many MTHFR folks, it gives them the benefits of natural folate but is easy to supplement as a pill form (which natural folate isn’t because it isn’t shelf-stable) and it metabolizes more slowly than 5-LMTHF, which means that most people have fewer side effects. 

Once you’ve taken folinic acid for a while you might be able to tolerate a small dose of 5-LMTHF because some of the accumulated problems from a functional folate deficiency have been worked out, so your body might be better able to handle it. Again, start low, go slow and change only one thing at a time. You might still find you can’t take 5-LMTHF, but this whole journey evolves so just because something was true when you began the journey doesn’t mean it will be true three months in, three years in, or three decades in. Remember, MTHFR is for life.

Next week we’ll talk about dosing strategies because for many of us, taking the same dose every day isn’t a great idea. After that, we’ll dive deeper into what to expect when you first start taking 5-LMTHF, what to do if symptoms arise, and how to manage any reactions you might be having.

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I Can’t Take Folate – Now What?

We all know that MTHFR mutations are differences in the way your body processes folate, so obviously the answer is to take more or better folate supplements like 5-LMTHF or folinic acid just like every doctor out there talks about. It’s so exciting to have a solution to the health issues that you’ve been struggling with! The problem is, there is a significant chunk of MTHFR folks out there who just don’t tolerate folate and never will. Truly, never. If you’re not sure why not being able to tolerate folate would matter in MTHFR, then read the Start Here Guide to MTHFR.

Who Can’t Take Folate?

Typically these people are in the group of MTHFR folks who tend toward undermethylation. Undermethylators make up about 45% of the population and while some of them do tolerate folate in low doses in foods or even a very tiny dose in a supplement, many of them don’t tolerate any folate at all, not even in food. There are exceptions, of course including low-serotonin overmethylators.

Now How Do I Deal With MTHFR Issues?

You’ll recall that the whole methylation cycle is mostly accomplishing two goals. One is converting homocysteine to methionine (to avoid homocysteine buildup), and the other is making SAMe (a methyl-donor).

the MTHFR lifestyle matters because of the way these cycles all interconnect.

Bypass the Cycle

So, if you can’t convert homocysteine to methionine, and you can’t make SAMe, you can still get the cycle and all related processes going by taking methionine and SAMe. It’s a bit of a cheat, but it helps to solve that one very basic problem and for most people, boosts their mood tremendously.

But Why Is This Happening In The First Place?

For most undermethylators who don’t tolerate folate, it’s happening because their serotonin is just so low. This can happen to overmethylators too, but it’s far less common. The key issue is typically LOW SEROTONIN and folate of any kind makes the depressive symptoms of low serotonin worse.

The basic trouble is that folate, 5-LMTHF, and folinic acid (also folic acid, but I know you don’t allow any of that into your body because of this) have an epigenetic effect on the SERT transporter.

The SERT Transporter

The SERT transporter helps to re-uptake serotonin after it has been released, This is the target for the popular antidepressants called SSRIs – that stands for Selective Serotonin Reuptake Inhibitor (it’s essentially a SERT inhibitor).

Taking an SSRI or inhibiting SERT doesn’t change the amount of serotonin you have, but it changes how long it stays out there as a signal. The longer it’s out there, the more effect it has and the happier you feel.

Folate boosts serotonin production, but also speeds up reuptake so may actually net decrease the amount of benefit (happiness) you get from that serotonin.

Folate in all of it’s forms actually boosts SERT function so even though folate helps your body manufacture more serotonin through the BH4 pathway, it boosts re-uptake more, so the net effect feels like lower serotonin.

Boosting Serotonin Naturally (Or Less Naturally)

The great news is that often the people who don’t respond well to folate, do typically respond really well to supplements and often drugs that boost serotonin. These include:

  • St. John’s Wort
  • SAMe (so if depression is your primary concern, focus on finding the optimal dose of SAMe before you add other serotonin boosters).
  • Melatonin (which boosts serotonin indirectly by both helping sleep and also reducing serotonin conversion to melatonin.)
  • Tryptophan
  • SSRI Medications (although you may still experience side-effects).

Where Do I Start?

  1. Folic Acid – Like everyone else with MTHFR issues, start at the beginning, which is getting the toxic folic acid out of your diet. If you don’t tolerate high-folate foods or folate supplements, then foods fortified with folic acid are extra harmful to you.
  2. HIgh natural-folate foods – you might find you can tolerate some high-folate foods once the folic acid is gone. If not, that’s fine too, but it’s worth it to try. This gets you out of stage 1 of MTHFR balancing, which is the general stuff that is typically good for all mutants. If you want more detail, check here.
  3. Other B vitamins – a B supplement or multivitamin that doesn’t include folate or B12. The only ones I know of are from Seeking Health and can be purchased from Fullscript using the sidebar link. This is an affiliate link so I will get a small commission on the referral and I will offer you a 10% discount.
  4. Methionine – 500 mg at bedtime can make a world of difference on its own.
  5. SAMe – this can help with depression and energy levels so it’s a good next choice. (Methionine and SAMe can also be purchased from the link on the side, but they are also pretty easy to find in local health food stores.) As with everything else with MTHFR, start at a lower dose, and increase slowly. A good starting dose is 200 mg twice daily.
  6. Move to Stage 3 of MTHFR balancing – this is all working with your own individual symptom picture, so it very much depends on what you are working with right now.

What If Low Serotonin Doesn’t Sound Like Me?

Sometimes, even without low serotonin some MTHFR folks just don’t do well with high-folate foods or supplements like 5-LMTHF. In this scenario, it is still a good idea to try the steps above and if low serotonin (which usually feels like depression) isn’t the issue then you might be able to try a tiny dose of folinic acid, which for some reason is better tolerated in this situation. It still might not be right, but it is worth a try to see if we can get that cycle moving just a little bit. Otherwise, follow the Start Here for MTHFR guide.

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