The Slow COMT Roadmap
The Slow COMT Roadmap
Dear Slow COMTer,
The goal of this roadmap is to give you the most direct, straightforward, actionable slow COMT plan possible.
If you've already run genetic testing (like 23andMe or AncestryDNA), you may want to confirm that you're carrying the COMT V158M variant, especially the homozygous (Val/Val) or heterozygous (Val/Met) form, though the latter is less of a concern unless you have symptoms associated with slow COMT.
This roadmap assumes you do, and that you’ve either seen classic symptoms (overstimulation, supplement sensitivity, anxiety, insomnia, dopamine surges/crashes), or have confirmed your status with a reputable interpretation tool.
Just start at the top (Day 0), and progress sequentially down the page. Each supplement link goes directly to the (non-affiliate) supplement I would recommend on Amazon for that particular purpose.
Day 0: Foundation Phase
1. Optional Labs for Greater Precision
You do not need labs to use this roadmap, but if you want biochemical confirmation that slow COMT is functionally active, or if you’re sensitive to supplements and want to reduce trial and error, these markers are the most useful.
Homocysteine over 7 µmol/L suggests methylation backlog that can increase pressure on COMT.
Serum B12 under 650 pg/mL or elevated MMA indicates functional B12 deficiency that may affect dopamine balance and energy.
Serum folate under 10 ng/mL may justify adding folinic acid or food-based folate, especially if mood, drive, or recovery are low.
Plasma metanephrine or normetanephrine elevated supports impaired catecholamine clearance and confirms COMT burden.
Urinary VMA high points to norepinephrine buildup due to COMT slowdown; low VMA may suggest poor upstream dopamine production.
RBC magnesium under 5.2 mg/dL confirms a cofactor deficit affecting both COMT activity and dopamine receptor function.
Plasma zinc under 90 to 95 µg/dL warrants supplementation, especially if MTR or MTRR variants are present or if histamine and focus issues persist.
Serum copper low-normal (optional) may explain poor dopamine-to-norepinephrine conversion in DBH-related cases.
Whole blood histamine or plasma methylhistamine elevated suggests histamine buildup often seen in slow COMT with DAO or HNMT variants.
Low SAM or elevated SAH on methylation panel reflects systemic methylation pressure that may interfere with COMT function.
2. Discontinue the Following Supplements:
