References and Methodology

Reference

References

Afterburners is built from a small number of recurring evidence domains rather than from isolated supplement claims.

Core evidence areas

Acetaldehyde toxicology — why acetaldehyde is treated as the active-clearance-window driver and a Group-1 carcinogen, separate from the next-morning experience in non-ALDH2*2 livers.
ALDH2 bottlenecks and saturation — why the second step in ethanol metabolism becomes rate-limiting and why NAD⁺ availability — not enzyme abundance — is the actual rate-limiter.
NAD⁺ depletion and redox imbalance — why the metabolic shadow of ethanol clearance persists into the morning long after acetaldehyde is gone.
Vasopressin suppression and electrolyte loss — why the sodium/potassium deficit dominates next-morning misery and is the single highest-leverage non-prescription lever.
Sleep architecture disruption from clearance during sleep — why drink timing dominates supplement choice for next-day function.
Glutathione depletion and the ALDH2-protection story — why GSH precursors matter for protecting Cys302 from auto-inactivation by acetaldehyde itself.
Gut barrier disruption and LPS translocation — why hangovers feel flu-like; the inflammatory tail is partly cytokine response to portal LPS.
CYP2E1 induction and ROS generation — why backup metabolism is dirtier than the primary pathway.
Cofactor depletion — why thiamine, magnesium, and related support compounds can matter without being primary interventions.

Selected citations

Eriksson CJP et al. Alcohol and Alcoholism 2020 — placebo-controlled human trial of L-cysteine-containing formulation, the trial that anchors the L-cysteine evidence (and which is best explained by the GSH-substrate mechanism, not bulk plasma trapping).
Salaspuro VJ, Hietala JM, Marvola ML, Salaspuro MP. Cancer Epidemiol Biomarkers Prev 2006;15:146–149 — slow-release buccal L-cysteine reduces salivary acetaldehyde by >90%, demonstrating that local-compartment trapping requires slow-release buccal/gastric format.
Hellström PM et al. Scand J Gastroenterol 2017 — slow-release L-cysteine gastric study; further evidence that the trap mechanism is real but format-dependent.
Trammell SA et al. Nat Commun 2016 — human pharmacokinetics of nicotinamide riboside; the foundation for using NR as a NAD⁺ precursor at supplement doses.
Martens CR et al. Nat Commun 2018 — chronic NR safety and NAD⁺-elevation study in healthy adults.
Conze D et al. 2019 — chronic NR safety follow-up.
Mackus M et al. Hum Psychopharmacol 2020 — RCT (n≈83) of DHM versus placebo for hangover symptoms; null result. The reason DHM is no longer Tier 1.
Scholey A et al. 2021 — second RCT (n≈20) of DHM versus placebo; also null. Reinforces the demotion.
Mahmood A et al. Gut 2007 — zinc carnosine reduces gut barrier permeability under indomethacin stress; the cleanest analog for the alcohol-induced version of the same problem.
Ebrahim IO et al. Alcohol Clin Exp Res 2013 — review of alcohol's effect on sleep architecture; the basis for the Tier 0 drink-timing prerequisite.

How the site uses that evidence

The site does not treat every ingredient as equivalent.

Tier 1 is reserved for direct or non-substitutable interventions.
Tier 2 supports the primary system.
Tier 3 and below preserve symptom-specific or long-tail coverage.

The practical way to use the research is:

1. Start with the correct protocol stage. 2. Use the mechanism pages to understand the failure mode. 3. Use ingredient pages for dosing, ranking, and context.

For the live substrate, see the generated ingredient and mechanism libraries: