1
Dehydration & Electrolyte Loss
Alcohol is an ADH (antidiuretic hormone) antagonist — it inhibits ADH production, causing the kidneys to excrete far more water than normal. For every standard drink, you lose approximately 100–150mL of excess urine. A big night out can produce a net fluid deficit of 1–2 litres, depleting Na⁺, K⁺, Mg²⁺, and Zn²⁺ simultaneously. This drives headache, muscle cramps, fatigue, and dizziness.
2
Acetaldehyde Toxicity
Alcohol is metabolised by ADH (alcohol dehydrogenase) into acetaldehyde — a highly toxic intermediate compound. Acetaldehyde is approximately 30× more toxic than ethanol itself. It causes DNA damage, protein adduct formation, mitochondrial dysfunction, and triggers release of inflammatory cytokines. Flushing, nausea, and tachycardia are hallmarks of acetaldehyde accumulation.
3
Inflammatory Cytokine Cascade
Alcohol disrupts gut barrier integrity, allowing bacterial lipopolysaccharides (LPS) to translocate into the bloodstream. This triggers systemic release of TNF-α, IL-6, and IL-10 — the same cytokines that cause fever and malaise during infection. This is why a hangover feels like being "flu-sick": it is a genuine inflammatory state, not just tiredness.
4
Glutamate Rebound & Sleep Disruption
Alcohol potentiates GABA receptors (sedating) and inhibits NMDA glutamate receptors. When alcohol clears, glutamate rebounds — causing hyperexcitability, anxiety, light sensitivity, and REM sleep disruption. This "glutamate rebound" explains why hangover sleep is non-restorative despite its length.
5
Vitamin B & Antioxidant Depletion
Alcohol metabolism heavily consumes Vitamin B1 (Thiamine), B6 (Pyridoxine), and B12 — cofactors essential for energy metabolism and neurological function. Simultaneously, glutathione (the primary antioxidant) is depleted processing acetaldehyde, leaving cells vulnerable to oxidative stress. This is why post-alcohol fatigue is disproportionate to actual exertion.
