TOBIN domain · OXI

Oxidative Stress

Redox imbalance, mitochondrial dysfunction, ROS/RNS burden, antioxidant capacity, metabolic stress and lipid oxidation indicators.

Full description

Oxidative Stress is an imbalance between reactive oxygen and nitrogen species and the body's antioxidant defenses. It leads to damage to fats, proteins and DNA, and to poorer mitochondrial energy production.

In TOBIN, oxidative stress is the link between exposures and metabolic disease. High blood sugar, insulin resistance, smoking, pollutants, excess iron and chronic inflammation all add to the oxidative load.

Components

5 components

Mitochondrial function

C

Mitochondria make cell energy (ATP) and are the main source of reactive oxygen species.

How it works: Overfeeding, inactivity and some toxins impair the electron transport chain, increasing leakage of free radicals and fatigue.

How it is assessed

  • · Exercise tolerance and fatigue history
  • · Lactate and specialty testing only when clinically indicated

Glycemic and lipid oxidation

A

High glucose forms advanced glycation end-products (AGEs); oxidized LDL drives atherosclerosis.

How it works: AGE–RAGE signaling triggers inflammation; oxidized LDL is taken up by macrophages to form plaque.

How it is assessed

  • · HbA1c, fasting glucose, insulin, HOMA-IR
  • · ApoB, triglycerides, HDL

Antioxidant defenses

B

Glutathione, superoxide dismutase, catalase and dietary antioxidants (vitamins C and E, carotenoids, polyphenols).

How it works: Glutathione needs cysteine, glycine and selenium; SOD needs zinc, copper and manganese.

How it is assessed

  • · Diet quality (fruit and vegetable intake)
  • · Selenium and zinc where deficiency is suspected

Methylation and homocysteine

B

Raised homocysteine reflects low folate, B12 or B6 and promotes oxidative damage to blood vessels.

How it works: Homocysteine auto-oxidizes, producing hydrogen peroxide, and impairs nitric oxide.

How it is assessed

  • · Homocysteine (above 15 µmol/L is elevated)
  • · B12, folate

Sleep and circadian rhythm

B

Short or irregular sleep raises oxidative and metabolic stress.

How it works: Sleep restriction reduces insulin sensitivity by 20–30% within days and raises markers of oxidative stress.

How it is assessed

  • · Sleep hours and regularity (journal)
  • · Screen for sleep apnea

Clinical bottom line: Antioxidant pills (vitamin E, beta-carotene) have not prevented heart disease or cancer in large trials, and beta-carotene raised lung cancer risk in smokers. The best evidence is for removing the drivers — glucose control, exercise, sleep, not smoking — and for a diet rich in vegetables.

What it covers

  • · Mitochondrial & redox function
  • · Antioxidant capacity
  • · Metabolic & glycemic stress
  • · Lipid oxidation markers
  • · Sleep & recovery load

Symptoms and exposures scored

4 questions
  • · How many hours do you usually sleep?
  • · How often do you feel exhausted even after rest?
  • · How many days a week do you exercise?
  • · Do you smoke, vape, or spend time around tobacco smoke?

Lab ranges

Graded 0–100 against published cutoffs
TestGrading points (value → concern 0–100)Source
HbA1c% · higher is worse5.6→0 5.7→40 6.5→80 8→100glycemic stressADA Standards of Care: 5.7–6.4% prediabetes, ≥6.5% diabetes range
Fasting glucosemg/dL · higher is worse99→0 100→40 126→80 180→100glycemic stressADA: 100–125 mg/dL impaired fasting glucose, ≥126 diabetes range
ApoBmg/dL · higher is worse90→0 100→40 130→80 160→100atherogenic lipid loadACC/AHA & ESC: ApoB ≥130 mg/dL is a risk-enhancing factor
Triglyceridesmg/dL · higher is worse149→0 150→30 200→60 500→100metabolic lipid stressNCEP ATP III: 150–199 borderline, 200–499 high, ≥500 very high
HDL cholesterolmg/dL · lower is worse50→0 40→40 30→80 20→100low protective lipidNCEP ATP III: <40 mg/dL low (men), <50 (women)
ALTU/L · higher is worse33→0 40→30 80→60 200→100hepatic loadACG: upper limit of normal ≈ 29–33 U/L (men), 19–25 (women)
GGTU/L · higher is worse50→0 100→50 200→100hepatic and oxidative loadTypical laboratory upper limit ≈ 50 U/L
Homocysteineµmol/L · higher is worse10→0 15→60 30→100methylation / B-vitamin strain>15 µmol/L elevated in most laboratory references
Reverse T3ng/dL · higher is worse24→0 30→50 40→100stress / illness pattern of T4 conversionTypical reference 9–24 ng/dL; guidelines (ATA) do not recommend rT3 for routine diagnosis — grade D
Total cholesterolmg/dL · higher is worse199→0 200→30 240→60 300→100lipid loadNCEP ATP III: <200 desirable, 200–239 borderline, ≥240 high
LDL cholesterolmg/dL · higher is worse99→0 130→30 160→60 190→100atherogenic cholesterolACC/AHA 2018: ≥190 mg/dL severe; 160–189 high; optimal <100
Non-HDL cholesterolmg/dL · higher is worse129→0 160→40 190→70 220→100atherogenic cholesterolNLA: non-HDL <130 mg/dL desirable
LDL particle number (LDL-P)nmol/L · higher is worse1000→0 1300→40 1600→70 2000→100atherogenic particle burdenNMR LipoProfile (Labcorp): <1000 optimal, 1300–1599 borderline-high, ≥1600 high; MESA
Small LDL-Pnmol/L · higher is worse527→0 700→50 1000→100small dense LDL (insulin-resistance pattern)NMR LipoProfile: ≤527 nmol/L reference
LDL particle sizenm · lower is worse20.5→0 20.3→40 19.5→100small LDL pattern BNMR: >20.5 nm pattern A, ≤20.5 pattern B
HDL particle number (HDL-P)µmol/L · lower is worse30.5→0 26→50 20→100low protective particlesNMR LipoProfile: ≥30.5 µmol/L reference
Lp(a)nmol/L · higher is worse75→0 125→50 250→100inherited atherogenic particleACC/AHA & EAS 2022: ≥125 nmol/L (≥50 mg/dL) risk-enhancing; measure once in lifetime
sdLDL-C (small dense LDL)mg/dL · higher is worse30→0 40→40 60→100small dense LDLDenka assay (Quest Cardio IQ, Boston Heart): <30 mg/dL optimal (lab-specific)
Lp-PLA2 activitynmol/min/mL · higher is worse123→0 150→50 225→100vascular inflammationPLAC Activity test (FDA-cleared): >123 nmol/min/mL higher risk
Oxidized LDLU/L · higher is worse60→0 70→50 100→100lipid oxidationLab-specific (Cleveland HeartLab ~<60 U/L); research-grade, grade C

Formulas

  • Symptom score = average answer (0–4) × 25
  • Lab score = 0.6 × worst marker + 0.4 × average marker
  • O score = 60% symptoms + 40% labs (whichever exists if only one)
  • HOMA-IR = fasting glucose (mg/dL) × fasting insulin (µIU/mL) ÷ 405; above about 2.5 suggests insulin resistance (Matthews 1985)
  • Bands: 0–33 lower · 34–66 moderate · 67–100 higher

Symptom score = average of your answers in that domain (0–4 scale, shown as 0–100). Lab score = 0.6 × the most out-of-range marker + 0.4 × the average of that domain's markers, where each marker is graded 0–100 against published clinical cutoffs. When both exist, the domain score = 60% symptoms + 40% labs. If you logged your journal in the last 14 days, 20% of the score comes from it: daily symptoms (I, O), sleep under 7 hours (O, B), low energy (N, O) and low mood (B).

Conditions where this domain weighs heavily

iClinical organizational scores based on the TOBIN framework. They group signals for review and are not validated diagnostic instruments or a medical diagnosis.

iDetection of an exposure does not establish that it caused a disease. This platform separates exposure, association, plausible mechanism, clinical evidence and demonstrated causation.

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