For how we live.
The human intestinal-permeability literature lists endurance exercise, NSAIDs, pregnancy and surfactants as stressors. Coffee is not on that list, and alcohol's case is largely inferred.
Two meta-analyses tie an extra two cups a day to roughly a third lower risk of both liver cancer and cirrhosis, with decaf showing a smaller effect. It is all observational, and the evidence quality is graded very low.
The FDA's threshold traces to a Health Canada assessment and a 2017 systematic review of 381 studies. It describes a population, not a person, and the variation between people is large.
Pooled data across 38 studies found higher coffee intake linked to a higher risk of heart attack — but a lower risk of stroke and irregular heartbeat, with a separate benefit for people with high blood pressure.
A 131,821-person cohort followed for up to 43 years and a dose-response meta-analysis of 450,000 people converge on roughly two to three cups — and diverge sharply above it.