When Active Isn’t Enough: Why B6 Fails Under Oxidative Stress
Guidance for Clinical Assessment of Micronutrient Dysregulation under Oxidative Stress
This clinical IP is offered openly for patient and provider empowerment, under active copyright. Attribution is expected.
You’re exhausted. Your labs look “normal.”
Your provider says you’re probably just stressed.
But you’ve done your homework. You know B6 is essential for mitochondrial function, neurotransmitter balance, and detox. You’re even using the “active” form, P5P (pyridoxal-5-phosphate), to bypass conversion problems.
So why do you still feel like garbage?
Because even active B6 fails in a terrain burdened by oxidative stress, micronutrient imbalance, and mitochondrial dysfunction. Here’s why.
B6 Must Be Dephosphorylated to Be Absorbed
Even the “active” form of B6 (P5P) isn’t absorbed as-is.
It must be dephosphorylated by intestinal alkaline phosphatase (IAP) before entering circulation.
But oxidative stress changes everything:
IAP is zinc-dependent
IAP is suppressed by inflammation and oxidative stress
So, if your redox terrain is collapsed, or zinc is depleted, your gut isn’t primed to absorb B6 properly at all.
PLP Function Still Depends on Redox Integrity
Even if you do absorb some B6, it’s just the beginning.
Inside the cell, PLP:
Binds to dozens of enzymes (for heme synthesis, neurotransmitters, amino acid metabolism)
Must remain stable in a redox-friendly environment
Under oxidative stress?
PLP is degraded to pyridoxic acid
Enzymes lose function due to low NADPH, FAD, and magnesium
Zinc depletion destabilizes PLP binding and activity
Translation? You’re pouring active B6 into a system that can’t use it.
What to Do Instead
Before assuming you're "B6 deficient," assess:
Zinc and copper balance
Magnesium status
Markers of oxidative stress (ferritin, GGT, lactate, etc.)
If PLP is still necessary, consider sublingual dosing (which bypasses the gut) or co-administer with cofactors that support enzyme activity. This is a conversation to be had with your provider before deciding on any supplementation.
I've made clinical handouts to help you:
Order the right labs
Understand how terrain blocks B6
Guide conversations with your provider
Get the Patient + Provider Handouts:
B6, Ferritin, Iron and Mitochondrial Dysfunction Lab Handouts:
Zinc and Copper Lab Handouts: