Wednesday, April 23, 2014

Side Effects from MTHFR supplements

It was brought to my attention by a few people that some people can experience side effects from taking too much 5-MTHF (active folic acid) - also known as over-methylation.  This is not common however it is still possible.  For most it means starting at a much lower dose.  The side effects apparently are more common among people with bipolar disorder.  I have yet to find out WHY the 5-MTHF can cause over-methylation - it is my experience that taking excess B vitamins (of which 5-MTHF is part of) is excreted from the body without harmful side effects.  According to Dr. Lynch however the over methylation can be due to other genetic mutations the person is unaware that they have.  One such TSW warrior had tested positive for the MTHFR gene mutation but his health care practitioner noted that other genetic mutations were more concerning and took priority. 

Where does that leave my research?  Well, basically it means I have a lot more research to do on other genetic disorders to see if they could possibly be related to TSW.  I personally do not plan to go out and determine if I have a bunch of other genetic mutations at this point.  I still believe that the MTHFR gene mutation is a big factor in TSW.  So far 2 people have tested negative according to my poll and 9 have tested positive.  Is it possible the 2 negative results were only tested for the 2 more common mutations and not for all potential 40-50 MTHFR genetic mutations?  Or is it that they are negative but maybe positive on another mutation like the TSW warrior mentioned above?  Or is there no correlation whatsoever?  While genetics is a very black and white science, it is also a very complex science. 

As for symptoms to watch out for in the event of over methylation - here is what Dr. Lynch has on his website (

Methylfolate Side Effects

Methylfolate is a remarkable nutrient yet it can create significant side effects.
Those who have MTHFR mutations (especially the C677T MTHFR mutation) learn that methylfolate is critical to take. The issue is methylfolate can cause more harm than good if not started at the right time or tapered up slowly in amount.
There appear to be three types of responses to methylfolate:
FIRST: A person who can jump on methylfolate and feel absolutely wonderful. The only down side they experience is why didn’t they know about methylfolate before?!
SECOND: A person starts methylfolate has an amazingly incredible week where they are happy, interacting and alert. Then the second week comes and they switch to wanting to hide in a room by themselves or literally throw dishes across the room out of anger. Or they may become bed ridden from muscle aches, intense headaches or joint pain.
THIRD: A person takes a small amount of methylfolate and feels all the methylfolate side effects right out the gate.

Methylfolate Side Effects:

  • irritability
  • insomnia
  • sore muscles
  • achy joints
  • acne
  • rash
  • severe anxiety
  • palpitations
  • nausea
  • headaches
  • migraines

Why does methylfolate create such an amazing week and then create such severe side effects so soon after?
It has to do with methylation, pre-existing inflammation and other genetic mutations which exist yet you’ve no idea they do.
This gets complicated quickly so I am going to keep it simple.
If you experience any of the above methylfolate side effects, I highly recommend you discuss it with your physician and get your dose of methylfolate reduced significantly or stopped for a week or two before reintroducing it.
UPDATE November 16, 2013
There are two three things you can do to quickly quench most of the methylfolate side effects:
  1. Consider 50 to 100 mg of time-released niacin. This is 1/4 of a tablet. Why? Niacin is broken down by SAMe. This means that excessive SAM is quenched by taking niacin. Niacin also helps break down glutamate and therefore increase GABA.
    • NOTE of CAUTION: You may experience flushing for 20 to 30 minutes. This is not harmful and is a result of histamine release. Since you are likely overmethylated, your histamine flush will likely be minimal – especially as this is time-released niacin.
  2. Consider 1 to 2 capsules of 250 mg of liposomal curcumin to help quench inflammation. If one takes methylfolate before inflammation is controlled, the methylfolate will worsen it.  One may consider taking 2 capsules of Optimal Turmeric three times a day during times of inflammation.
  3. Consider Hydroxocobalamin as it is an excellent sponge for reducing nitric oxide levels. Methylfolate increases nitric oxide levels – which is why it is so effective in reducing headaches, pain, cardiovascular disease risk, thrombosis, preeclampsia, periodontal disease, etc – but at the same time, excessive nitric oxide levels are harmful as they end up producing serious radical damage via nitrotyrosine. Hydroxocobalamin quenches nitric oxide quite effectively.

It is very important that any genetic treatment be done under a trained healthcare practitioner. 


  1. I read your post, it really very nice explanation as well as great review like that. Thank you so much for sharing with us.

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