Methyl Mayhem – Are your histamine symptoms actually a methyl reaction?

Symptoms are sneaky.  One symptom like nausea can have what seems to be hundreds of different potential causes.  An upset tummy could be related to stress, food allergies, histamine intolerance, food poisoning, overeating or undereating, medications or supplements, infections, injuries.  All kinds of possibilities!!

And that's where figuring out your puzzle can be the hardest.  If you don't know some of the potential causes of a symptom, you don't even know to go looking for it.  

The same applies to symptoms of food sensitivities and histamine intolerance.  And today we're going to take a look at a totally different potential cause of those symptoms - a methyl reaction.

A methyl reaction, or over-methylation, is what happens when some of your biochemistry is blocked and methylfolate backs up because it can't be swooped up into the next biochemical pathway and put to good use.  

We've talked about a lot of genetics in this blog and how important it is to have the whole system balanced together.  But we've really just focused on histamine and there is so much more involved!  (That's why we tend to mess things up when we focus on the function of just one gene, like MTHFR.)  

A methyl reaction may feel a little different for every individual - because we are all unique! - but here are some more common symptoms:

  • Headaches and Migraines
  • Nausea
  • Muscle aches and pains
  • Joint pain
  • Irritability
  • Anxiety
  • Mood swings
  • Sweating
  • Insomnia
  • Feeling revved up
  • Eye sensitivity and discomfort
  • List Element

Any of those sound like your food sensitivity or histamine intolerance symptoms?  Again, there can be a bunch of different causes for a symptom, but if a lot of these sound like your typical reaction perhaps you should consider the possibility of a methyl reaction as the cause.  

Most commonly I see folks have a methyl reaction when they're trying to supplement methylfolate or methylcobalamin (B12) after they learn they have an MTHFR variant.  In fact, most providers will tell you to start methylfolate immediately if you have an MTHFR SNP!  For some that's like flipping the mysterious switch and they feel amazing.  And then for some of us, we start having those symptoms listed above but no one warned us they might sneak in.  At that point how do you know what is causing what symptom?

Anyone can experience a methyl reaction, even if your MTHFR genes are just fine.  That's because of epigenetics - things like the foods we eat, the stress we live with and the environmental exposures we have.  Any of those things will also cause a change in how biochemistry works and cause a methyl block which causes methyl reactions.  

The big question now is how to make the symptoms go away, right?!  How can we figure out if the symptoms are from sensitivities and intolerances or methyls?  Niacin (or niacinamide) to the rescue!  As our body metabolizes niacin, it uses those excess methyls  in our biochemistry.  (And if you recall, niacin also helps to support your body's efforts to clear histamine!)

The things to know about taking niacin for a methyl reaction:

  1. Like any supplement, I always recommend starting at a low dose with niacin so you can learn how it serves you.  For niacin that may be 50mg per dose.  Any supplement or medication we take is making a change in biochemistry so we need to be mindful when we start something new.  It may not agree with you.  If that's the case you're not doing anything wrong…you may just need some additional support in figuring this one out.   
  2. You may not notice anything at all with one dose or it may make a huge difference.  Symptoms may get better and then come back again; again, totally normal.  The goal is to keep taking niacin regularly, e.g. every 1-2 hours, until your symptoms are pretty well gone.  Once you get to this point, you may consider keeping a standard dose in your daily routine. 
  3. This will only work if you also stop all methyl-donor supplements which are things like methylfolate, methylcobalamin, betaine, TMG, and SAMe.  There are many others, but these are the most common.  Oh…and quercetin!  If you're reacting to too many methyls, then putting them in right now may not be the best idea anyway.  Figuring out the reason why you're reacting to methyls will allow you to address it and then you can put that folate back in.
  4. Niacin will very likely cause a flush at some point while you're taking it.  That means your ears, face and neck are going to turn red, get warm and feel prickly or tingly.  For me, even my legs and arms get itchy and tingle a bit.  It sounds a lot like an allergic reaction, doesn't it?  It's actually just niacin increasing the blood circulation in your skin - totally normal and safe.  In fact, most folks who try the niacin and flush also observe it is easier to breathe while they are flushing (as opposed to breathing with bad allergies).  If you just can't deal with the thought of a flush, consider trying niacinamide which is another form of the same vitamin which will accomplish the same outcome (a little more slowly) but without the flush.  
  5. It is possible to get methyl reactions after eating wonderfully healthy foods like leafy greens, beets, liver and many others.  Any foods which are high in the same methyl donors listed above have the potential to cause methyl reactions.  Don't let this scare you away from eating these foods…just be aware of how you feel after you eat them and consider it may be related to methyls and not food sensitivities!

OK.  So…you tried the niacin and it did actually help!  Now what?  Take niacin forever?  This is when it really does make sense to get a little support from someone who knows how this stuff works (and how it feels).  If you want some help with this one, consider contacting me for some personalized wellness coaching.  Available even if you're not in South Carolina!  (That's home for me.)

And if the niacin makes no difference at all after about 4-5 days (usually it takes 1-2 days to notice a difference), then you have some level of confidence that methyls are not an issue for you…and the search continues.  

Sixty-second Self-care Tip…

So many of us are taking handfuls of supplements every day…but do you know what is in each one of them?  Since we're talking methyl reactions today, why not take a look at what you're taking and see if you're quietly taking a bunch of methyls.  Maybe just that will help relieve 50% or more of your food sensitivity or histamine intolerance reactions!

Got your supplements lined up for inventory?  Here's what to look for:

  • Methionine
  • Methylfolate (MTHF)
  • Methylcobalamin (B12)
  • Betaine
  • Trimethylglycine (TMG)
  • Dimethylglycine (DMG)
  • SAMe
  • DMSO
  • MSM
  • Choline

Next step?  Consider taking them out of the routine for a while, add a little niacin and see how things change for you.

Questions?  You know you can always email me at  That's the same way you can contact me for personalized wellness coaching, too.  I'm here for you!


60-second self-care, biochemistry, epigenetics, food sensitivities, histamine intolerance, methyl donors, methyl reaction, methylfolate, MTHFR, niacin

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