SAMe Responder (Undermethylation)
In the first half of the methylation cycle, the amino acid Methionine is converted to homocysteine through the intermediaries SAMe [s-adenosylmethionine], and SAH [s-andenosyl homocysteine].
It is the SAMe that donates the methyl group to multiple biochemical reactions and the SAH that is a potent inhibitor of methylation.
When this side of the cycle is functioning poorly, we now refer to this as SAMe Responders for scientific correlation with the appropriate biochemistry (historically referred to as Undermethylators) .
The usual reason for poor functioning here is likely that the enzyme responsible for the initial conversion, Methionine Adenosyltransferase (MAT), carries a minor genetic defect, Single Nuclear Polymorphism (SNP), and thus cannot function at full measure.
This step is Magnesium-dependent and the conversion should be aided by magnesium supplementation.
From observational data it seems likely these patients have certain personality traits that are very different to those without this defect. They are referred to as “SAMe Responders” and with training with experienced practitioners, and a degree of experience, clinicians can pick SAMe Responders with a carefully taken clinical history.
Biochemical confirmation is difficult. One of the multitudes of biochemical reactions involving methylation is the metabolism of histamine which has to be “methylated” to be broken down. A slightly elevated histamine would be in keeping with “SAMe Responders”. Histamine is an indicative test, not fully accurate. There are now more detailed ways to measure methylation status. Other tests for methylation need to be done carefully due to the reactivity of the amino acids. It is also more expensive and not covered by a medical rebate. Patients already on antidepressant/antihistamine medications will not get a reliable methylation test as medications influence the result. All testing is an indicator, not a diagnosis.
For the reasons stated above ‘SAMe Responders” would be likely to show clinical improvement by supplementation with Magnesium, SAMe and in some cases methionine.
It is also hypothesised that this group are relatively low in serotonin and thus more likely to respond favourably to the Selective Serotonin Reuptake Inhibitor (SSRI) type medication. Therefore, caution should be used as Serotonin-norepinephrine reuptake inhibitors (SNRI) medication may create an exacerbation of symptoms.
There is a theory that after treatment commences for SAMe Responders, there may be changes which trigger oxidative stress, which may trigger a short term high urinary pyrrole measurement. This is yet to be researched but can be observed by 6 monthly Urinary tests until the urine is clear of pyrrole.
It has been observed in the literature that a number of people with depression respond well to S-adenosyl methionine. The Pfeiffer/Walsh clinic found these people that respond well to SAMe tended to be those with high histamine.