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 provides valuable insight for those seeking to increase mental acuity through dietary supplements.
Athletes and fitness enthusiasts often use dietary supplements such as caffeine and creatine to enhance performance. Caffeine is known for its ability to reduce fatigue and increase alertness. Creatine, especially creatine monohydrate, helps rapidly replenish adenosine triphosphate (ATP), which is essential for short bursts of high-intensity exercise. Creatine nitrate, a newer form, is thought to provide the benefits of creatine while also increasing nitric oxide production, which can improve blood flow and muscle oxygenation.
Despite the known benefits of these supplements individually, the effects of their combination have been less studied. Some evidence suggests potential interactions that may enhance or diminish their benefits. In their new study, the researchers aimed to evaluate the cognitive and physical performance effects of weekly high-dose caffeine, creatine nitrate, and their combination in resistance-trained men.
“I was intrigued by the potential ergogenic and cognitive benefits of creatine and caffeine, which are well documented individually but less well understood when combined. Given their popularity among athletes, it was important to explore whether their combination could provide 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 was conducted at Jacksonville State University’s Human Performance Laboratory. Recruitment targeted resistance-trained males with at least two years of multi-joint resistance training experience. Participants were asked to maintain their usual exercise and diet habits and avoid new exercise or dietary changes during the study.
The final sample included 12 participants, aged 18 to 40 years, who met strict inclusion criteria. They had to be free of metabolic disorders, cardiovascular disease and other specific health conditions, and not on prescription drugs. 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 exercise tests and provided baseline health data. The study followed a crossover, double-blind, placebo-controlled design, with participants cycling through four treatment phases: creatine nitrate, caffeine, their combination, and a placebo. Each phase lasted seven days, separated by a one-week washout period.
Supplements included 5 grams of creatine nitrate, 400 milligrams of caffeine, a combination of the two, or a maltodextrin placebo. These were administered 45 minutes before the exercise tests. The rationale for the doses was based on previous research showing that these amounts could improve performance and cognitive function.
Performance was assessed using bench press and leg exercises, measuring repetitions to failure and lift volume. The Wingate test, a 30-second cycle ergometer sprint, assessed indicators of anaerobic performance such as peak power, average 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 analogue scale to assess their willingness to perform, along with 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 such as peak power and average power, remained unchanged in all conditions. These findings suggest that while supplements may improve cognitive function, they do not provide additional benefits for physical performance.
“I was surprised to find that taking creatine nitrate and caffeine together did not significantly improve exercise performance, as we first hypothesized. This is in contrast to previous findings suggesting potential ergogenic benefits from these supplements, highlighting 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 Word-Color Stroop Test. This improvement was more pronounced than with caffeine alone. The combined treatment showed a medium to large effect size, indicating a strong impact on cognitive processing.
“The main 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 seeking only improvements in physical performance may not see additional benefits.”
While this study provides important insights, it has several limitations. The sample size was relatively small and limited to resistance-trained men, who may not represent broader or more diverse populations. The washout period between treatments, although practical, may have been too short to completely eliminate the effects of the previous phase of supplementation.
“A major caveat of our study is its relatively small sample size and focus on male resistance-trained athletes, which may limit the generalizability of the findings,” noted Koozehchian. “Furthermore, the short duration of supplementation (seven days) may not have long-term effects, and we did not measure peak blood levels of caffeine and nitrates, which may affect the results.”
Future research could explore the effects of these supplements over longer periods and in more diverse populations. Longitudinal studies may also help to understand how these supplements affect muscle growth, intramuscular signaling pathways, and hormonal responses over time.
“Longer term, I intend to explore the effects of these supplements over longer periods and in more diverse populations, including different athletic and non-athletic groups and both genders,” explained Koozehchian. “Furthermore, investigating the underlying mechanisms through which these supplements affect cognitive and physical performance may 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 cognitive and physical performance.
The study, “Effect of creatine nitrate and caffeine individually or in combination on exercise performance and cognitive function: A randomized, crossover, double-blind, placebo-controlled trial,” was authored by Gina Mabrey, Majid S. Koozehchian, Andrew To Newton, Alireza Naderi, Scott C. Forbes, and Monoem Haddad.
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