TOBIN Intelligence Library · evidence review

Iron Deficiency & Anemia

Iron deficiency is the most common nutrient deficiency worldwide. Ferritin under 30 ng/mL indicates depleted stores even before anemia; hemoglobin falls later. A cause — blood loss, malabsorption (celiac, H. pylori) or low intake — should always be sought.

What is well established

4 links
  • Blood loss (menstrual, gastrointestinal) → Depleted iron storesA

    Each mL of blood lost removes about 0.5 mg of iron.

    Established causal · Multiple high-quality guidelines or meta-analyses

  • H. pylori or celiac disease → Iron malabsorptionA

    Mucosal damage and reduced gastric acid impair non-heme iron absorption; eradication or gluten-free diet restores it.

    Established causal · Multiple high-quality guidelines or meta-analyses

  • Chronic inflammation → Functional iron restriction via hepcidinA

    IL-6 raises hepcidin, blocking iron export; ferritin may be falsely normal when CRP is high.

    Established causal · Multiple high-quality guidelines or meta-analyses

  • Iron deficiency → Fatigue, low mood, restless legsB

    Iron repletion improves fatigue in non-anemic women with low ferritin (RCTs).

    Randomized evidence · Moderate clinical evidence

What is suspected, not proven

0 links

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

    Domain emphasis

    N Nutrition · 1B Hormonal Balance · 0.7I Inflammation & Infection · 0.7O Oxidative Stress · 0.6T Toxins · 0.3

    H. pylori is a true bacterial cause here — test and treat it when iron deficiency is unexplained.

    Related Quadpandemics

    • I · Estrogen & Endocrine Disruption

      Endocrine-active chemicals are widely measurable in the population; their health effects must be evaluated exposure by exposure.

    • II · Obesity & Metabolic Dysfunction

      Obesity is a signaling and exposure problem, not a number on a scale.

    • IV · Anxiety, Depression & Neurobehavioral Health

      Mood symptoms are assessed responsibly — never automatically attributed to toxins or hormones.

    Labs that inform this review

    • Fasting insulin (2.0–8.0 µIU/mL) — Insulin signaling load; pairs with glucose for HOMA-IR. Marked elevation with symptoms warrants clinician review.
    • ApoB (< 90 (lower if high risk) mg/dL) — Atherogenic particle count; better risk discrimination than LDL-C alone. Persistently high values deserve a cardiovascular risk discussion.
    • TSH (0.4–4.0 mIU/L) — First-line thyroid signaling test. Any abnormal result should be confirmed and reviewed clinically.
    • 25-OH vitamin D (30–60 ng/mL) — Nutrient status relevant to immune and musculoskeletal function. Severe deficiency with bone pain or falls needs clinical review.
    • Ferritin (30–300 ng/mL) — Iron stores, but also an acute-phase reactant. Iron deficiency in adults needs a source investigation.
    • Estradiol (Cycle- and sex-dependent pg/mL) — Central to Pandemic I assessment, interpreted with cycle timing. Interpretation requires a clinician who knows your cycle and medication context.
    • Free T4 (0.8–1.8 ng/dL) — Circulating thyroid hormone; confirms whether an abnormal TSH reflects true thyroid under- or over-function. Low free T4 with symptoms, or any high value with palpitations, needs clinician review promptly.
    • Free T3 (2.3–4.2 pg/mL) — Active thyroid hormone, formed mostly by conversion of T4 in tissues. High free T3 with low TSH suggests hyperthyroidism — see a clinician.
    • Reverse T3 (9–24 ng/dL) — Inactive T4 metabolite that rises in stress, illness and calorie restriction. Do not change thyroid medication on rT3 alone; discuss with a clinician.

    Score cutoffs used

    • HbA1c ADA Standards of Care: 5.7–6.4% prediabetes, ≥6.5% diabetes range
    • Fasting insulin Common functional reference; interpret only with a true fasting sample
    • TSH ATA/Endocrine Society: 0.4–4.5 mIU/L; >10 overt range
    • 25-OH vitamin D Endocrine Society: <20 ng/mL deficient, 20–29 insufficient; IOM <12 deficient
    • Ferritin AGA 2020: ferritin <45 ng/mL supports iron deficiency; WHO <15 depleted
    • Vitamin B12 <200 pg/mL deficient; 200–300 borderline (confirm with MMA)
    • Magnesium (serum) Serum reference ≈ 1.7–2.2 mg/dL; serum underestimates total body stores
    • Omega-3 index Harris & von Schacky: >8% desirable, <4% undesirable
    • Homocysteine >15 µmol/L elevated in most laboratory references
    • Free T4 Typical reference 0.8–1.8 ng/dL (assay-specific); interpret with TSH (ATA)
    • Free T3 Typical reference 2.3–4.2 pg/mL; low T3 also occurs in illness and calorie restriction
    • Reverse T3 Typical reference 9–24 ng/dL; guidelines (ATA) do not recommend rT3 for routine diagnosis — grade D
    • Anti-TPO antibodies Common cutoff >34–35 IU/mL (assay-specific); marks Hashimoto's risk (ATA)
    • Thyroglobulin antibodies Common cutoff ≤4 IU/mL (Roche) — assay-specific; positive in ~60–80% of Hashimoto's
    • Small LDL-P NMR LipoProfile: ≤527 nmol/L reference
    • LDL particle size NMR: >20.5 nm pattern A, ≤20.5 pattern B
    • sdLDL-C (small dense LDL) Denka assay (Quest Cardio IQ, Boston Heart): <30 mg/dL optimal (lab-specific)

    Key formulas and thresholds

    Published clinical cutoffs
    • HOMA-IR = fasting glucose (mg/dL) × fasting insulin (µIU/mL) ÷ 405 — above 2.5 suggests insulin resistance (Matthews 1985).
    • BMI = weight (kg) ÷ height (m)² — 25–29.9 overweight, 30 or more obesity (WHO); lower cutoffs (23/27.5) for many Asian populations.
    • Waist-to-height ratio = waist ÷ height — 0.5 or more signals central adiposity (NICE 2022).
    • TG/HDL ratio = triglycerides ÷ HDL (mg/dL) — above 3 is associated with insulin resistance (observational).
    • HbA1c (%): concern above 5.6, scored 100 at 8 — ADA Standards of Care: 5.7–6.4% prediabetes, ≥6.5% diabetes range
    • Fasting insulin (µIU/mL): concern above 8, scored 100 at 40 — Common functional reference; interpret only with a true fasting sample
    • TSH (mIU/L): concern above 4.5, scored 100 at 20; concern below 0.4, scored 100 at 0.01 — ATA/Endocrine Society: 0.4–4.5 mIU/L; >10 overt range
    • 25-OH vitamin D (ng/mL): concern below 30, scored 100 at 5 — Endocrine Society: <20 ng/mL deficient, 20–29 insufficient; IOM <12 deficient
    • Ferritin (ng/mL): concern below 30, scored 100 at 5; concern above 300, scored 100 at 1000 — AGA 2020: ferritin <45 ng/mL supports iron deficiency; WHO <15 depleted
    • Vitamin B12 (pg/mL): concern below 300, scored 100 at 100 — <200 pg/mL deficient; 200–300 borderline (confirm with MMA)
    • Magnesium (serum) (mg/dL): concern below 1.8, scored 100 at 1.2 — Serum reference ≈ 1.7–2.2 mg/dL; serum underestimates total body stores
    • Omega-3 index (%): concern below 8, scored 100 at 3 — Harris & von Schacky: >8% desirable, <4% undesirable
    • Homocysteine (µmol/L): concern above 10, scored 100 at 30 — >15 µmol/L elevated in most laboratory references
    • Free T4 (ng/dL): concern below 0.9, scored 100 at 0.5; concern above 1.8, scored 100 at 3.5 — Typical reference 0.8–1.8 ng/dL (assay-specific); interpret with TSH (ATA)
    • Free T3 (pg/mL): concern below 2.5, scored 100 at 1.8; concern above 4.4, scored 100 at 7 — Typical reference 2.3–4.2 pg/mL; low T3 also occurs in illness and calorie restriction
    • Reverse T3 (ng/dL): concern above 24, scored 100 at 40 — Typical reference 9–24 ng/dL; guidelines (ATA) do not recommend rT3 for routine diagnosis — grade D
    • Anti-TPO antibodies (IU/mL): concern above 34, scored 100 at 500 — Common cutoff >34–35 IU/mL (assay-specific); marks Hashimoto's risk (ATA)
    • Thyroglobulin antibodies (IU/mL): concern above 4, scored 100 at 200 — Common cutoff ≤4 IU/mL (Roche) — assay-specific; positive in ~60–80% of Hashimoto's
    • Small LDL-P (nmol/L): concern above 527, scored 100 at 1000 — NMR LipoProfile: ≤527 nmol/L reference
    • LDL particle size (nm): concern below 20.5, scored 100 at 19.5 — NMR: >20.5 nm pattern A, ≤20.5 pattern B
    • sdLDL-C (small dense LDL) (mg/dL): concern above 30, scored 100 at 60 — Denka assay (Quest Cardio IQ, Boston Heart): <30 mg/dL optimal (lab-specific)

    iThese thresholds organize where to look; they do not diagnose. Laboratory ranges, age, sex and pregnancy change interpretation.

    Published sources

    Guidelines and landmark studies