Thiamine
Thiamine
Generic Name
Thiamine
Mechanism
- Cofactor for enzymatic reactions: Acts as the active form, thiamine pyrophosphate (TPP), in key metabolic enzymes:
- Pyruvate dehydrogenase – links glycolysis to the citric acid cycle.
- α‑Ketoglutarate dehydrogenase – essential for oxidative decarboxylation in mitochondria.
- Transketolase – facilitates the non‑oxidative phase of the pentose‑phosphate pathway, maintaining redox balance.
- Neuroprotection: Adequate TPP ensures neuronal energy production and protects against ischemic damage; deficiency leads to demyelination and axonal degeneration.
Pharmacokinetics
| Parameter | Details |
| Absorption | Oral: ~70 % after 200 mg, reduced with high doses or in the presence of food. Parenteral: 100 % bioavailability. |
| Distribution | Widely distributed in extracellular fluid; limited crossing of the blood‑brain barrier (reduced in disorder). Half‑life: < 3 h; accumulates in plasma with repeated dosing. |
| Metabolism | Phosphorylated intracellularly to TPP; dephosphorylated by thiamine pyrophosphatases. |
| Excretion | Primarily renal; 90 % unmetabolized excreted in urine. Reduced clearance in renal impairment prolongs half‑life. |
Indications
- Deficiency prevention: Chronic alcoholism, malnutrition, bariatric surgery, prolonged parenteral nutrition lacking thiamine.
- Deficiency treatment: Beriberi (wet/dry), Wernicke encephalopathy, Wernicke‑Korsakoff syndrome, *SMA type 1* (rare), and certain cases of refractory seizures linked to thiamine deficiency.
- Adjunctive therapy: Diabetic neuropathy, myocardial ischemia (historical use), and septic shock in select protocols.
Contraindications
- Contraindications: None formally documented; use caution in severe renal impairment to avoid prolonged accumulation.
- Warnings:
- Rapid IV supplementation can trigger Wernicke’s encephalopathy recurrence (rare if adequate pre‑emptive dosing used).
- Drug interactions: Attenuated effect of ketorolac when supplemented orally; potential interference with metformin metabolism (minimal).
- Renal dysfunction: Monitor excretion; adjust dose accordingly.
Dosing
| Setting | Dose | Route | Frequency |
| Adults for deficiency | 100–200 mg IV/IM | IV/IM | 3× daily for 3–7 days, then maintenance |
| Maintenance post‑recovery | 50–100 mg | IV/IM | 1× daily |
| Oral prophylaxis | 50 mg | Oral | 1× daily |
| Parenteral nutrition supplementation | 1.5–3 mg/kg BSA | Continuous infusion | 24 h daily |
Tip: For Wernicke encephalopathy, start with 200 mg IV three times daily for 3 days, then 100 mg IV or IM 3× daily until recovery.
Adverse Effects
| Adverse Effect | Incidence | Notes |
| Allergic reaction (rash, urticaria) | Rare | Monitor IV infusion rate; pre‑medicate if history of reactions. |
| Headache | Low | Often transient, resolves with continued doses. |
| Hypotension | Rare, IV | Slow infusion rate, monitor vitals. |
| Severe hypoglycemia | Very rare | In patients on insulin or oral hypoglycemics, due to enhanced glucose utilization. |
| Fluid overload | Rare in high‑dose IV | Safeguard in heart failure patients. |
Monitoring
- Clinical: Improvement of neuropathic pain, muscle weakness, cardiac output, or neurocognitive status.
- Laboratory:
- Serum or plasma thiamine levels (if available) before and after therapy.
- CBC and electrolytes (for high‑dose IV groups).
- Renal function tests when dosing in CKD.
- Imaging (for Wernicke encephalopathy): MRI may show characteristic thalamic lesions; reassess after 1–2 weeks of therapy.
Clinical Pearls
- Water‑solubility means excess thiamine is rapidly excreted – no need for a loading dose in healthy individuals, but high doses are safe for severe deficiency.
- Oral vs. IV: Oral bioavailability diminishes >200 mg due to saturation; therefore, for acute deficiency, IV/IM is preferred.
- Bariatric patients often miss not only thiamine but also other B‑vitamins – include this vitamin in routine supplementation protocols.
- Intravenous thiamine can paradoxically *trigger* neurological improvement even after prolonged deficiency, but start early to avoid neurogenic shock.
- Check for hidden alcoholism in unexplained beriberi/sepsis protocols; often the underlying cause is undiagnosed alcohol use disorder.
- In sepsis scoring, low thiamine is associated with worse outcomes; consider early supplementation in high‑risk ICU patients.
- Exogenous pyruvate (e.g., in metabolic acidosis) competes with thiamine for transporters; be mindful if giving both concomitantly.
Key Takeaway: Thiamine is a low‑risk, high‑yield supplement that corrects a spectrum of deficiency syndromes—from subtle neuropathy to catastrophic Wernicke encephalopathy—when dosed appropriately by weight, route, and disease severity.