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MTHFR, Methylation and Histamine in Psychiatric Conditions

Misconceptions about the clinical significance of the MTHFR mutation.

Judy Tsafrir MD
Source: Judy Tsafrir MD

Methylation is a vital foundational biochemical process in the body, involved with the detoxification of heavy metals, regulation of gene expression and protein function, and central to the synthesis of neurotransmitters, the chemical messengers which mediate mental and emotional states. Imbalances in methylation status result from genetic defects in the enzymes which regulate the process of methylation. In the past few years there has been a great deal of interest in genetic testing, and in particular, the role of the MTHFR gene. A genetic defect of the MTHFR gene can result in a malfunctioning MTHFR enzyme, which can affect methylation.

There is a common misconception, however, that the mere presence of an MTHFR mutation is synonymous with a methylation defect. This is by no means necessarily the case, even if an individual is homozygous for the gene. The presence of the defective gene does not necessarily translate into a functional defect. In fact, the recent wide spread indiscriminate prescription of methylfolate to compensate for the genetic mutation is not only misguided, but can actually make low serotonin people who are undermethylated not only feel much worse, but also increase their risk of developing cancer.

In order to determine the actual functional methylation status in the body, whole blood histamine must be measured. Histamine levels correlate with the functionality of the methylation process. Histamine and methyl are inversely related to one another. That is to say, if whole blood histamine is low, the individual will be overmethylated and if it is high, they will be undermethylated. The protocols to treat the two conditions are different.

Some symptoms and traits of undermethylation:

Chronic depression, history of perfectionism, seasonal allergies, history of oppositional defiance, high libido, adverse reaction to benzodiazepines and folic acid, good response to SSRI’s and anti-histamines, sparse body hair, suicidal tendencies, addictiveness, phobias, denial of illness, obsessive compulsive tendencies, ritualistic behaviors, strong willed, self-motivated during school years, history of competitiveness in sports, strong willed, calm demeanor but high inner tension, family history of high accomplishment, frequent headaches, slenderness, dietary inflexibility, terse speech

Some symptoms and traits of overmethylation:

High anxiety/panic, hyperactivity, rapid speech, low libido, religiosity, tendency to be overweight, nervous legs, pacing, adverse reaction to SSRI’s and SAMe, improvement with benzodiazepines, dry eyes and mouth, low motivation during school years, depression, self mutilation, sleep disorder, tinnitus, hirsutism, food/chemical sensitivities, artistic or musical ability, copper overload, estrogen and antihistamine intolerance, absence of seasonal allergies

I learned about the natural treatment of methylation disorders from a brilliant pioneer, Dr. William Walsh, a biochemist and founder of the Walsh Research Institute in Chicago. The Walsh Research Institute offers invaluable training for physicians in his method. Many psychiatric conditions can be effectively treated with protocols of nutrients: vitamins, minerals, amino acids and fatty acids. The protocols allow some patients to wean off of pharmaceuticals entirely or to reduce the dosages of the medications that they are taking. Dr. Walsh has written a book about his approach called "Nutrient Power". These days I rarely see a patient in my practice without making use of his method. It must be noted that simply substituting nutrient protocols for pharmaceuticals is not nearly as effective as a holistic approach; including appropriate nutrition, healing the gut, treating infections, attending to life style factors, including sleep and movement, and addressing the emotional and spiritual life of the patient.

As I have gained more experience asking patients about their symptoms, I have begun often to be able to accurately predict what the lab studies will reveal. No one has all of the symptoms, and sometimes it can be confusing, as a person will have symptoms or traits of both conditions.

Methylation defects take three to four months to correct, and longer in people with the blood type A. The protocols do not correct the genetic defect, and thus need to be taken indefinitely. Multi-vitamins, which typically contain folic acid, are also harmful to those who are undermethylated. I was interested to learn that many foods typically considered super healthy, such as leafy greens and avocados, and other foods that are high in folate are not beneficial for low serotonin undermethylators. In addition, those with under methylation do more poorly on diets which exclude animal protein.

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