QUESTION: I have an insomnia patient who has both methylation and COMT defects, and I can’t seem to get them to sleep better. When I added in 5-MTHF supplementation, their sleep got worse! They are currently on Ambien, and want to get off, but in the light of their genetics, what do I do?

ANSWER: Methyl defect + COMT defects is extra tricky… SNP at COMT means that 1/2 or less catecholamine removal than normal, at least. When you methylate them, they form Epi and can’t get it out fast enough, since the only back up to MAO is COMT, and they are generally poor sulfation people too.

You have to saturate the cofactors for the back up detox pathways first so they tolerate the methyl support.

Sulfation is Molybdenum dependent and MAO is B2 and B6 dependent. I typically stop all methyl donors for a time to up-regulate the Catecholamine and SO4 back ups THEN add slowly (the methyl support).

Sulfation and MAO supportive cofactor supplementation plan:
Molybdenum: 200-400mcg QD to BID
Riboflavin: 5-phosphate 65-100mg BID
P5P: 100 mg bid

Then start the Methyl support with a balanced formula at LOW dose (like Ben’s formula or Methyl Guard Plus etc) Never give a COMT injured person 5MTHF alone.

Regarding getting people off of sleep medicines: (this is my 2 cents based on trying to taper people off these GABA meds for a couple decades) The immediate release non-benzodiazepines [Eszopiclone – Lunesta (Sepracor)] ; [Zaleplon – Sonata (Monarch/King)]; [Zolpidem – Ambien (sanofi-aventis)] = Work via a slightly different mechanism from the Benzo drugs (i.e. the have somnolence but no real anti-seizure properties) – but both classes bind at subunits of the GABAa receptor (not GABAb). In the quest for better sleep aid with less neuromuscular inhibition the evolution from Barbiturate, to Benzo to non-benzo targeted more specific portions of the GABAa subcomplex. So all have similar side effects (amnesia, tolerance and addiction, etc etc.) In trying to get a patient off these you have to work very slowly if they have been on them longer than 6-12 months. (If less than a year you may be able to do it in 2-3 months). In those on these longer than 12 months it can take 3-6 months in a motivated person, and longer at times.

Some people just go cold turkey, and do fine. Many cannot get off them that way. For those who can’t do it cold turkey, you have to use a broad approach in many cases. Sleep hygiene, dietary advice, exercise and all the rest are crucial. As for neurochemical support they often need step down medications and/or natural substances (or both) to ease them off their medications.

The targets of these step down alternative substances should support the other somnolent portions of the brain including agonism of GABAb (not-a), Glycine, and in some people support for serotonin-melatonin pathways, Histamine modulation, and inhibition of Glutamate and [if appropriate] support of methylation defects (unless the person has a COMT snp).

GABAb (not-a) – Baclofen
Glycine receptors – glycine
GABA a&b Maintenance – Tyrosine
GABA a agonist – Pregnenolone for men and Progesterone for women
Serotonin – melatonin = Tryptophan, B6, Niacinamide, B5, Trazadone, Remeron, Tricyclics, melatonin
Histamine = H1 and maybe H2 blockers
Methyl donors
Inhibition of Glutamate class = Magnesium, Theanine, Serotonin support

Less specific agents = Kava, Gabapentin etc etc

If need be (and over 12 months use of the med it is commonly necessary) you need to taper the Ambien etc. We try 50% decrease nightly for a 4-8 week period while adding the collaborative support Rxs above. In most cases then you can drop the dose by another 50% for 4 + weeks then taper either off or to every other day. Some people go faster and some slower –its pretty individual obviously.

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