Slow Clearance Pattern
When detox pathways run slowly, compounds linger. Caffeine, hormones, medications, toxins—they all stick around longer than they should.
What this pattern means.
Your body clears things more slowly than average. This isn't a defect—it's a different metabolic speed that requires different inputs.
The analogy
Think of it like a slow drain. Water still goes down—it just takes longer. If you pour water in faster than it drains, the sink overflows.
The solution isn't to "speed up the drain" (you can't change your genes). It's to pour less water in and give the system time to clear.
Genes in this pattern.
Slow COMT = dopamine, norepinephrine, epinephrine, and catechol estrogens linger longer
Met/Met (Val158Met) = slowMAO-A
Monoamine breakdownLow activity = serotonin, dopamine, norepinephrine clear slowly
Low activity variantsNull = can't conjugate certain toxins via this pathway
Null genotype (~50% of people)Slow variants = reduced toxin conjugation capacity
Ile105Val affects activityNAT2
AcetylationSlow acetylator = drugs and aromatic amines clear slowly
Slow acetylator phenotypeSlow = caffeine affects you for hours; certain drugs accumulate
Slow metabolizer variantsPoor metabolizer = ~25% of drugs affected; may need dose adjustments
Poor metabolizer phenotypeUGT1A1
GlucuronidationGilbert's variant = slower bilirubin clearance; affects some drugs
Gilbert's syndrome (*28/*28)You don't need all of these to have the pattern. Even 2-3 slow genes can create the effect.
Common signs.
- •Caffeine sensitivity (jittery, can't sleep if you drink it past noon)
- •Alcohol intolerance or prolonged hangovers
- •Medication sensitivity (need lower doses)
- •Perfume/chemical sensitivity
- •Histamine intolerance symptoms
- •Estrogen dominance signs
- •Anxiety or feeling 'wired'
- •Slow recovery from stress
- •React strongly to supplements
Note: These signs can have other causes. The pattern is suggested when multiple signs cluster together AND genetic testing shows relevant variants.
The classic example: COMT + caffeine.
This illustrates how slow clearance creates sensitivity.
Fast COMT + caffeine
- • Caffeine boosts catecholamines
- • COMT clears them quickly
- • Effect is brief, manageable
- • Can drink coffee late in day
- • May need caffeine to feel alert
Slow COMT + caffeine
- • Caffeine boosts catecholamines
- • COMT clears them slowly
- • Effect is prolonged, intense
- • Coffee after noon = no sleep
- • Already naturally alert
Same caffeine, different genes, completely different experience.
Strategies for slow clearance.
Reduce Inputs
If clearance is slow, reduce what needs to be cleared. Less caffeine, alcohol, processed foods, environmental toxins.
Support Phase II
Ensure adequate glutathione (NAC, glycine), sulfate (Epsom salt baths, MSM), and amino acids for conjugation.
Don't Overload Phase I
Avoid things that speed up Phase I without supporting Phase II. Some supplements and foods induce CYP enzymes.
Manage Stress
Stress hormones use the same clearance pathways. Chronic stress depletes capacity for everything else.
Support Methylation
COMT needs SAMe to work. If methylation is compromised, COMT slows further. B vitamins, especially.
Optimize Bile Flow
Conjugated toxins exit via bile. Support with bitter foods, adequate fat, and possibly bile support supplements.
The upside.
Slow clearance isn't all bad. There are real advantages.
Better focus (slow COMT)
Higher baseline dopamine in the prefrontal cortex = better working memory and focus (in calm environments).
Medication sensitivity
Need lower doses = less side effects, lower cost. Many people are overmedicated because dosing assumes average metabolism.
Early warning system
You notice toxic exposures that others ignore. This sensitivity can protect you if you listen to it.
"Slow clearance isn't a defect. It's a signal to reduce inputs and support the system."← Back to all patterns