In adolescent male athletes, the ACE DD genotype is associated with a markedly reduced ergogenic response to acute caffeine ingestion, with only 33.3% of DD carriers showing improved endurance performance compared to 77.5–84.6% of DI and II carriers.

People with the ACE DD genotype have fewer fatigue-resistant muscle fibers that rely on oxygen, so when they take caffeine, it doesn't stimulate their muscles or nervous system as effectively. Caffeine normally blocks a chemical that slows down nerve signals and muscle activity, but in DD carriers, this effect is weak because their muscles don't respond well to the signal to burn fat for energy or to work harder. As a result, their endurance doesn't improve much after caffeine, while others with different gene versions get a strong boost.