NADH/NAD+ disruption
What it is
Ethanol metabolism via ADH + ALDH produces 2 NADH per ethanol molecule. Normal cellular NADH/NAD+ ratio is ~0.01; ethanol dramatically shifts this toward NADH.
Downstream consequences
Gluconeogenesis inhibition
- NADH elevation inhibits the malate-aspartate shuttle and LDH reverse reaction
- Blocks conversion of lactate → pyruvate → glucose
- Net effect: hypoglycaemia (particularly on empty stomach) + lactate accumulation
- This contributes to fatigue, brain fog, dizziness during hangover
Fatty acid metabolism disruption
- NADH inhibits β-hydroxyacyl-CoA dehydrogenase
- β-oxidation slowed → fatty acids accumulate
- Accumulated NADH + acetate drive fatty acid synthesis
- Early stage: hepatic steatosis (fatty liver)
Redox feedback loop
- Peroxisomal β-oxidation also generates NADH
- Creates a feedback inhibition loop limiting ethanol oxidation rate
- Catalase pathway (uses H₂O₂) does NOT produce NADH — may help mitigate redox stress
Hangover contribution
Hypoglycaemia from NADH/NAD+ disruption is a direct contributor to next-day:
- Fatigue and weakness
- Brain fog and impaired executive function
- Difficulty concentrating
Recovery
NADH/NAD+ ratio normalises as ethanol clears — timeline depends on dose and metabolic capacity.