As with every scientific study, correlation is not causation. Your list of symptoms may be related to anything and everything other than a methylation problem. Undermethylation may be nothing more or less than complete and total speculation. We barely understand how the human body works and this wisdom is reflected by ever-changing nutritional advice (such as whether we should eat gluten) and failure to cure cancer. Correlations aren’t justification to launch into the random usage of drugs and substances. There are countless biochemical processes going on in our body each second, and your state of methylation may only be one factor influencing your energy, mood, bowel function, immunity and more.

High histamine is usually brought about by metabolic imbalances that results from many factors like lack of B6 that acts as a cofactor to convert histadine to histamine, gut bugs that cause elevated histamine, ingested histamine, oestrogen levels (high estrogen will elevate histamine levels and high histamine can elevate estrogen levels) so there is so much more to histamine levels than just methylation.

“Where I think the Pfeiffer protocol falls down is that methylation only affects intracellular histamine levels via the HNMT (histamine N-methyltransferase) it does not take into consideration extracellular histamine breakdown via DAO (diamine oxidase). Also histamine receptors 1 to 4 can also impact neurological histamine levels. when considering histamine levels and methylation we need to be looking at the big picture. Many factors affect histamine breakdown and production and its not all about methylation. Histamine has far reaching effects on the body. I think the Pfeiffer protocol which says high histamine = undermethylation and low histamine means overmethylation is too simplistic. I also don’t believe there is any such thing as ‘overmethylation’ . I think these people produce the same amount of methyls as the next person but they can’t utilise them effectively so I would prefer to use the term underutilisation.” – Carolyn Ledowsky, MTHFR Support Australia.

We need to remember, with all studies and anectodes, the effects of placebo. Half of all drugs that fail FDA approval in late-stage trials drop out of the pipeline due to their inability to beat placebo. Therefore, feelings of improvement as the result of taking supplements specific to “methylation issues” may be the result of placebo. On the flip side, feelings of ill-health may be the result of learning that you have a MTHFR polymorphism or by self-diagnosing via doctor google. 

Undermethylation is perhaps both science and quackery at the same time, or neither science or quackery. Human biology doesn’t lend itself to simple compartmentalisation. It’s not as simple as “over or under” when discussing methylation cycles. But it may good starting point for the individual. Methylation is but a small part of the whole equation. Methylation does not operate in isolation of other biological functions.

Find a good practitioner to test whether you have legit deficiencies and if you do, supplements are warranted where good food and lifestyle choices have already been exhausted.

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