The health evidence for extra virgin olive oil is substantial, but it was generated almost entirely from olive oil consumed as an ordinary part of the diet. In PREDIMED, participants at high cardiovascular risk were randomised to a Mediterranean diet supplemented with EVOO or nuts versus a low-fat control, with the EVOO arm supplied roughly one litre per week and instructed to use at least about 50 mL per day in normal cooking, dressings and meals. Higher olive oil intake was associated with substantially lower cardiovascular event and mortality risk. The EFSA authorised claim for olive oil polyphenols protecting blood lipids from oxidative stress is likewise expressed as a daily intake threshold (at least 5 mg hydroxytyrosol and derivatives per 20 g of oil), with no condition regarding timing, fasting state, or co-ingestion with lemon.

Searches for trials of the specific format, an EVOO plus lemon shot taken on an empty stomach in the morning, returned no randomised or controlled human studies testing that delivery method against oil taken with food. Even retailer marketing pages that promote the ritual concede that no clinical trials exist on the ritual itself.

On absorption, the evidence points in the opposite direction to the "fasted shot is superior" idea. Human crossover trials show carotenoid absorption from salads is markedly higher with fat-containing dressings than fat-free ones, and monounsaturated-fat dressings required the least fat for maximum carotenoid uptake. That mechanism requires the fat and the carotenoid-containing food to be eaten together, which favours drizzling oil on food over drinking it separately from meals.

On the most common rationale offered for the lemon and oil combination, "flushing" gallstones or the liver, The Lancet analysis found that the objects passed after such regimens were not gallstones but soap-like material formed from the ingested oil and juice, and independent fact-checking bodies reach the same conclusion.