A Nootropic Hiding in the Urine of Coffee Drinkers

Athletes of all performance levels regularly consume over-the-counter energy drinks containing caffeine and other so-called cognitive enhancing nutrients (usually sugar, some vitamins, and a mixture of herbs of unproven value) before or even during exercise. They hope the caffeine will help their cognitive focus and alertness and improve athletic performance.

Unfortunately, the benefits of ingesting caffeine before exercise are often variable depending on the amount consumed, the other ingredients in the drink, the contents of the stomach, the number of times that someone has used energy drinks previously (called tolerance), the duration of the exercise, the person’s age and health status, and the rate at which each person’s liver metabolizes the caffeine.

Ironically, subjects who metabolize caffeine the fastest also demonstrate a bigger cognitive and performance boost than those subjects who metabolize it slower. This seems counterintuitive. The slow metabolizers should have more caffeine in their blood, not less. What’s going on?

Humans metabolize caffeine quickly and almost completely into one fascinating molecule called paraxanthine, which is responsible for coffee's benefits. Studies in humans show that, as compared to caffeine, paraxanthine is less toxic, has a smaller effect on blood pressure and heart rate, and produces far fewer unpleasant gastrointestinal side effects. Paraxanthine binds to receptor sites better than caffeine and produces considerably more locomotor activation.

Caffeine has a well-known protective and effective effect on dopamine neurons in the brain. This explains why drinking lots of coffee reduces the probability of developing Parkinson’s disease. However, recent studies have shown that paraxanthine provides greater protection of dopamine neurons than caffeine. Furthermore, the wake-promoting action of paraxanthine is greater and lasts longer than those produced by caffeine.

Does paraxanthine have greater benefits than caffeine regarding athletic performance or cognitive function?

One study reported that ingesting 200 mg of paraxanthine enhanced memory, reaction time, and attention for up to six hours in healthy male and female adults. In addition, subjects could safely consume paraxanthine for many days with no apparent side effects. In mice, paraxanthine supplementation increased muscle mass, strength, and endurance. It’s not known whether humans show similar physical benefits.

A recent study investigated whether taking paraxanthine prior to exercise may serve as an effective nootropic and enhance physical performance, stamina, or recovery from exertion. The benefits of paraxanthine were compared to caffeine ingestion to determine whether paraxanthine supplementation has independent and/or synergistic effects on cognition (Yoo et al., 2024). Interestingly, co-ingesting paraxanthine and caffeine did not provide additive benefits. The results of the study indicated that paraxanthine may have nootropic effects that are independent of caffeine.

These recent findings clearly demonstrate that paraxanthine is a safe and effective nootropic and athletic performance-enhancing nutrient. Paraxanthine can improve measures of executive function and reduce cognitive fatigue before and after exercise. In conclusion, paraxanthine may be considered a feasible alternative to caffeine to help preserve cognitive function during prolonged exercise (Wenk, 2021).