High Oxidative Load
When antioxidant defenses can't keep up with oxidative stress, damage accumulates. Fatigue, inflammation, and accelerated aging follow.
What this pattern means.
Oxidative stress is a normal byproduct of metabolism—especially in mitochondria. Your body has antioxidant enzymes to neutralize it. When these systems are compromised, reactive oxygen species accumulate and damage cells.
The cascade
1. Superoxide forms → SOD converts it to hydrogen peroxide
2. H2O2 accumulates → CAT and GPX convert it to water
3. If the cascade is slow → H2O2 becomes hydroxyl radical (very damaging)
4. Damage products form → GST enzymes conjugate them for removal
Weakness at any step creates a bottleneck. The system is only as strong as its weakest link.
Genes in this pattern.
SOD2
Mitochondrial superoxide → hydrogen peroxideVal16Ala affects how efficiently superoxide is cleared in mitochondria
Val/Val may have reduced mitochondrial importSOD1
Cytoplasmic superoxide → hydrogen peroxideHandles superoxide outside mitochondria. Copper/zinc dependent.
Rare mutations cause ALS; common variants have modest effectsCAT
Hydrogen peroxide → waterWorks downstream of SOD. If SOD is fast but CAT is slow, H2O2 accumulates.
Promoter variants affect expression levelsGPX1
Glutathione peroxidaseUses glutathione to neutralize peroxides. Selenium-dependent.
Pro198Leu affects enzyme activityNull genotype = can't conjugate certain oxidative byproducts
Null in ~50% of peopleImportant for clearing products of oxidative damage
Ile105Val affects substrate specificityNQO1
Quinone detoxification*2 variant has zero enzyme activity. Can't detoxify quinones from smoke, pollution.
*2/*2 = no function (~4-20% depending on ethnicity)PON1
ParaoxonaseProtects LDL from oxidation. Important for cardiovascular health.
Q192R affects activity and substrate specificityCommon signs.
- •Fatigue, especially after exercise
- •Slow recovery from workouts
- •Chronic low-grade inflammation (elevated CRP)
- •Premature aging signs (skin, joints)
- •Environmental and chemical sensitivity
- •Frequent infections or slow healing
- •Brain fog or cognitive decline
- •Elevated oxidative stress markers (8-OHdG, F2-isoprostanes)
- •Low glutathione on testing
- •Sensitivity to alcohol
The NQO1 example.
This shows how a single gene can have dramatic effects on oxidative stress handling.
Normal NQO1 (*1/*1)
- • Efficiently detoxifies quinones
- • Handles benzene, cigarette smoke metabolites
- • Protects against certain cancers
- • Normal response to some chemotherapy drugs
NQO1 *2/*2 (null)
- • Zero enzyme activity
- • Can't detoxify quinones at all
- • Higher benzene toxicity risk
- • May need to avoid certain environments
4-20% of people are *2/*2 depending on ethnicity. It's common—but consequential.
Strategies for high oxidative load.
Support Glutathione
GPX needs glutathione to work. NAC, glycine, and glutamine support synthesis. Whey protein provides cysteine.
Selenium for GPX
GPX is selenium-dependent. Brazil nuts (1-2/day) or 200mcg selenium. Don't overdo it—selenium toxicity is real.
Reduce Oxidative Inputs
Processed foods, seed oils, pollution, smoking, excessive exercise, chronic stress—all increase oxidative load.
Mitochondrial Support
CoQ10, PQQ, and alpha-lipoic acid support mitochondrial antioxidant systems where SOD2 works.
Polyphenols & Nrf2
Sulforaphane, curcumin, and polyphenols activate Nrf2, which upregulates your own antioxidant production.
Don't Over-Antioxidant
Some oxidative stress is necessary for adaptation. Mega-dosing antioxidants can block beneficial hormesis.
The hormesis paradox.
Some oxidative stress is actually beneficial. Here's the nuance.
Exercise creates oxidative stress
This stress signals the body to build stronger antioxidant defenses. Taking high-dose antioxidants around workouts may blunt these adaptations.
Nrf2 activation needs some stress
Mild oxidative stress activates Nrf2, which upregulates your own antioxidant genes. Too much exogenous antioxidants can prevent this adaptation.
The balance
If you have high oxidative load pattern, you may need more support than average—but still not mega-doses. Focus on reducing inputs and supporting your own systems, not overwhelming them with exogenous antioxidants.
"High oxidative load isn't about lacking antioxidants. It's about reducing what's creating the load in the first place."← Back to all patterns