Creatine nitrate and caffeine combo boost cognitive performance, study finds

A new study published in the journal Nutrients has found that a combination of creatine nitrate and caffeine significantly enhances cognitive function more effectively than caffeine alone. However, this combination does not improve exercise performance. This research offers valuable insights for those seeking to enhance mental sharpness through dietary supplements.

Athletes and fitness enthusiasts often use dietary supplements like caffeine and creatine to boost performance. Caffeine is well-known for its ability to reduce fatigue and enhance alertness. Creatine, particularly creatine monohydrate, helps in quickly replenishing adenosine triphosphate (ATP), which is crucial for short bursts of high-intensity exercise. Creatine nitrate, a newer form, is thought to offer the benefits of creatine while also enhancing nitric oxide production, which can improve blood flow and muscle oxygenation.

Despite the known benefits of these supplements individually, the effects of combining them have been less studied. Some evidence suggests potential interactions that could either amplify or diminish their benefits. In their new study, the researchers aimed to evaluate the cognitive and physical performance effects of a week-long high-dose intake of caffeine, creatine nitrate, and their combination in resistance-trained males.

“I was intrigued by the potential ergogenic and cognitive benefits of both creatine and caffeine, which are well-documented individually but less understood when combined. Given their popularity among athletes, it was important to explore whether their combination could yield synergistic benefits, particularly for enhancing physical and cognitive performance,” said study author Majid Koozehchian, an associate professor of kinesiology at Jacksonville State University.

The study took place at the Human Performance Laboratory of Jacksonville State University. Recruitment targeted resistance-trained males with at least two years of multi-joint resistance training experience. Participants were required to maintain their usual training and dietary habits and avoid new exercises or dietary changes during the study.

The final sample included 12 participants, aged 18 to 40, who met strict inclusion criteria. They had to be free of metabolic disorders, cardiovascular diseases, and other specific health conditions, and not on prescription medications. They also had to have a body mass index (BMI) between 18.5 and 24.9 and no known intolerance to caffeine or natural stimulants.

Participants underwent a familiarization session where they practiced the exercise tests and provided baseline health data. The study followed a double-blind, placebo-controlled, crossover design, with participants cycling through four treatment phases: creatine nitrate, caffeine, their combination, and a placebo. Each phase lasted seven days, separated by a week-long washout period.

The supplements included 5 grams of creatine nitrate, 400 milligrams of caffeine, a combination of both, or a placebo of maltodextrin. These were administered 45 minutes before exercise tests. The rationale for the dosages was based on previous research showing these amounts could enhance performance and cognitive function.

Performance was assessed using bench press and leg press exercises, measuring repetitions to failure and lifting volume. The Wingate test, a 30-second cycle ergometer sprint, evaluated anaerobic performance indicators like peak power, mean power, and fatigue index.

Cognitive function was assessed using the Stroop Word–Color Test, which measures attention, processing speed, and cognitive flexibility. Participants also completed the Visual Analog Scale to rate their readiness to perform, alongside comprehensive questionnaires on sleep quality, caffeine tolerance, and side effects.

Blood samples were taken to measure various markers, including muscle and liver enzymes, and a complete blood count was performed. Heart rate and blood pressure were monitored before and after exercise.

Contrary to the researchers’ expectations, no significant improvements in exercise performance were observed. Bench press and leg press repetitions and volumes, as well as Wingate test parameters like peak power and mean power, remained unchanged across all conditions. These findings suggest that while the supplements may enhance cognitive function, they do not provide additional benefits for physical performance.

“I was surprised to find that the co-ingestion of creatine nitrate and caffeine did not significantly improve exercise performance, as we initially hypothesized. This contrasts with previous findings suggesting potential ergogenic benefits from these supplements, highlighting the complex interactions and the need for personalized approaches to supplementation.”

But the researchers found that the combination of creatine nitrate and caffeine significantly improved cognitive performance on the Stroop Word–Color Test. This enhancement was more pronounced than with caffeine alone. The combination treatment showed a medium-to-large effect size, indicating a robust impact on cognitive processing.

“The primary takeaway from our study is that while the combination of creatine nitrate and caffeine significantly improved cognitive function, particularly in tasks involving cognitive interference, it did not enhance short-term exercise performance. This suggests that athletes and individuals seeking cognitive benefits may consider this combination, but those looking solely for physical performance enhancements may not see additional benefits.”

While this study offers important insights, it has several limitations. The sample size was relatively small and limited to resistance-trained males, which may not represent broader or more diverse populations. The washout period between treatments, though practical, may have been too short to fully eliminate the effects of the previous supplement phase.

“A major caveat of our study is its relatively small sample size and the focus on male resistance-trained athletes, which may limit the generalizability of the findings,” Koozehchian noted. “Additionally, the short duration of supplementation (seven days) might not capture longer-term effects, and we did not measure peak blood levels of caffeine and nitrate, which could influence the outcomes.”

Future research could explore these supplements’ effects over longer periods and in more diverse populations. Longitudinal studies could also help in understanding how these supplements affect muscle growth, intramuscular signaling pathways, and hormonal responses over time.

“Long-term, I aim to explore the effects of these supplements over more extended periods and in more diverse populations, including different athletic and non-athletic groups and both genders,” Koozehchian explained. “Additionally, investigating the underlying mechanisms through which these supplements influence cognitive and physical performance could provide more nuanced insights.”

“I believe our findings contribute to the growing body of evidence supporting a personalized approach to supplementation. The interplay between different supplements and individual responses underscores the need for tailored strategies to optimize both cognitive and physical performance.”

The study, “The Effect of Creatine Nitrate and Caffeine Individually or Combined on Exercise Performance and Cognitive Function: A Randomized, Crossover, Double-Blind, Placebo-Controlled Trial,” was authored by by Gina Mabrey, Majid S. Koozehchian, Andrew T. Newton, Alireza Naderi, Scott C. Forbes, and Monoem Haddad.