Is 400mg of caffeine a day a safe threshold?

EFSA has published 3 years ago a document about the maximal safe daily doses of caffeine as well as the maximal doses recommended in one sitting. These figures have been estimated based on the brain and cardiovascular effects of caffeine. Indeed, EFSA concluded that for the general population 400 mg a day is a safe limit for caffeine intake. There are some differences for specific sets of the population as can be seen in the table below:

Type of population| Maximal dosage advised in one sitting (mg)| Maximal daily dosage advised (mg or mg/kg) 

Adults |200 mg (2 cups coffee) |400 mg (4 cups) 

Intense sports activity in adults |200 mg up to 2 h before the exercise |Not determined 

Pregnant women |200 mg (2 cups) |200 mg (2 cups) 

Nursing women |200 mg (2 cups) |200 mg (2 cups) 

Adolescents and children |Not determined |3 mg/kg 

These figures concern the specific types of population in general but there is also interindividual variability. We know that the population is divided in slow and fast metabolizers (polymorphism at the level of cytochrome P450 or CYP1A2 that metabolizes 95% of caffeine) and that some other polymorphisms present at the level of the main brain caffeine target, the adenosine A2A receptor or ADORA2, define the sensitivity of every individual to some effects of caffeine such as effects on sleep or anxiety levels. There are many other polymorphisms that are and will be progressively discovered. These polymorphisms are part of those that determine the quantity of caffeine consumed by every individual to obtain a balance between the desired effects of caffeine and the avoidance of potential negative side effects. 

400 mg is considered a safe limit that can be advised in most instances. In some persons really intolerant to caffeine, these doses might trigger unpleasant effects but this dosage has never been found to have harmful effects for health unless high to very high doses of caffeine (usually higher than these limits) are associated with alcohol, intense exercising (like dancing in hot surroundings like night clubs). This has been seen with energy drink abuse.