This is part 2.  Read part 1 here.

Methylation and Niacin

Phase 2 detoxification pathways are the routes through which our cells hook activated toxic substances up with small nutrient groups, neutralizing them and making them water-soluble so they can be eliminated in urine.  One of the major detoxification pathways is called methylation. Our detoxification pathways get overwhelmed by chemical assaults, some of them exacerbated by genetic polymorphisms (like MTHFR, but also those related to sulfation and glutathionation).

These days, it’s all the rage to blame all manner of histamine issue on gene polymorphisms such as MTHFR.  And that’s clearly playing a role in people’s elevated histamine issues and histamine intolerance – since those who have high histamine are undermethylated.

But as pharmacist and functional medicine practitioner Suzy Cohen points out, you can be undermethylated without the MTHFR polymorphism – because pharmaceutical medications can also compromise your methylation:

The biggest mistake you could make is thinking that methylation problems don’t apply to you because you don’t have the gene mutation . . . I assure you that your medicine has the capacity to mess up your methylation! (Source)

It’s also worth considering an alternative viewpoint on methylation, Anthony William’s perspective as a medical medium that:

The MTHFR gene mutation test is currently in its infancy and is not as accurate as the medical community believes. . . The MTHFR gene mutation test . . .  is just a basic test that reveals inflammation in the body. Although this test is given under the guise of a gene test and a real gene is being looked at, it is ultimately only able to indicate if there is inflammation in the body. . . The inflammation that triggers off a positive MTHFR gene mutation test stems from toxic byproduct wreaking havoc as it moves from the liver into the bloodstream. This can play a part in producing abnormal homocysteine levels. Eventually, this “dirty” blood prevents proper methylation or the conversion of folate or folic acid. (Source)
People can also be OVERmethylated and LOW in histamine.  While that’s not generally a problem people with migraine have (if their migraine is part of a picture of histamine intolerance or overload), using B vitamins such as methylfolate and methylcobalamin CAN eventually tip people into an overmethylated state.  At this point, niacin is very useful, because it mops up methyl. (For more information on overmethylation as compared to undermethylation, click here). 

But for those of us who are generally UNDERmethylated, taking a B complex vitamin that includes both methylated forms of B12 and Folate will be counterbalanced by the presence of the niacin.  And if the amount of niacin is very high, the total overall effect could theoretically result in a deepening of the methyl depletion.

So, it’s complex.

Some Additional Considerations Re: Niacin and Methylation


When I spoke with one of the formulators at NOW supplements, they explained to me that 1) quantities of niacin in B complex vitamins are formulated based on a general target market and the ratios presented by the marketplace and competition, as well as by recommended daily allowances set by the National Institutes of Health – B complexes are NOT formulated in ratios meant to prevent undermethylation or specifically for those with migraine.

Also, you can get migraine from both under-and-over methylation, though they are accompanied by different psychological states (undermethylated being more depressive, foggy, and lethargic – overmethylated being more amped and full of tension and anxiety).

There is more to migraine than methylation.


Niacin Can Both Trigger and Treat Migraine.
What is Going on Here?

The literature and anecdotal evidence for how niacin affects migraine is all over the board. There are case reports of people getting rid of headaches using high doses of niacin, as well as a few studies that show people getting resolution of migraine with niacin (some with intravenous niacin, some via the oral route). Finally, there are also anecdotal reports of people’s migraines being triggered by niacin.

There is more to consider about niacin than the fact that it is a methyl sponge. Niacin is also a “histamine liberator”, which might be why taking it would initially raise histamine but eventually clear it out.  The ability of niacin to clear out histamine (and glutamate) may explain its ability to benefit those with migraine.  Dr. Hoffer, the founder of Orthomolecular medicine and huge proponent of niacin, said:

“It is necessary to give enough (B3) to empty the histamine storage sites to a level at which there is no time to replenish them by the time the next dose is taken. It may require 6 to 8 grams per day for some people.” (Source)
As it turns out, niacin has been used to treat histadelia (high histamine), as well as histapenia (low histamine). Jonathan Prousky, ND, points out that:
Using niacin to treat histadelia might seem contradictory considering it will augment the release of histamine from basophils and tissue mast cells. However, there is evidence that the niacin flush is mediated by the release of prostaglandin D2 (PGD2) from dermal macrophages and not from degranulation of basophil and tissue mast cells. Further, Hoffer suggested that daily intake of niacin gradually lowers total body histamine by chronically depleting storage levels. Niacin has a complicated mechanism of action that modulates histamine release, lowers total blood histamine, and increases the production of PGD2. (Source)

What to Do?

Given that people with digestive-based migraines generally already have high histamine, LOW blood pressure, and blood vessel dilation, it seems logical that their symptoms would be exacerbated by niacin.  Because niacin depletes B6, which is needed to make the histamine-degrading enzyme DAO (diamine oxidase), additional supplementation with B6 may be beneficial for those choosing to supplement with niacin.

Upon reviewing all of this evidence for and against niacin, I initially felt very cautious about niacin, and thought it might even be the culprit B vitamin causing so many migraines in people who take a B complex. But ultimately, I’ve found that intellectual and research-based ideas of how beneficial something is only go so far.  Especially when the evidence is mixed or split as to different qualities of a substance, it comes time to experiment. This is where the rubber meets the road.

While everyone may react differently, my observation in clients taking niacin with migraine is that it is actually very beneficial.  It appears that its glutamate-lowering and serotonin-raising effects far outweigh its undermethylating and other effects, at least in those people with migraine who have excess glutamate as its cause. Furthermore, it appears that the flushing form of niacin works to abort migraine while the non-flushing forms do not.  I also found out that coffee contains a fair amount of niacin and this may be one reason it helps to get rid of migraine.  Intriguing!


Other Potential B Vitamin Migraine Triggers

I was always suspicious of methyl B12 as a stand-alone supplement, because I’ve personally experienced migraines triggered by B12. I have come across some evidence that B12 can be toxic in the presence of glutathione depletion.  Glutathione is our most powerful and abundant antioxidant in the body, and migraineurs are generally low in it. (As it turns out, triptans – the most popular drug for the treatment of migraine – also deplete glutathione.  This is another way of saying that triptans cause inflammation).

Not only folic acid, but also methylated forms of folate can be problematic also because they may increase glutamate and lower serotonin levels. The politics of methylfolate and which forms are available in supplement form as compared to prescription form are especially complex.

I will share more research on this topic in my online course, as well as my blog post on how I make my own customized vitamin B blend.This

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The information in this article is for educational purposes only and not meant to replace diagnosis, treatment, or prescription by a qualified medical professional.