In a recent study carried out at Jacksonville State University, a team of researchers from the United States, Iran, Canada and Qatar explored the complexities of these two popular sports nutrition supplements to understand how they might interact to affect training and exercise.
“In recent years, sports nutrition has become a more nuanced science concerning performance enhancement, issues of safety and legality,” they wrote in the journal Nutrients. “Among the extensively studied dietary supplements, caffeine and creatine independently are well supported to have ergogenic properties; however, the potential synergistic effects from their combined use are limited.”
Secondary outcomes included assessing the impact of these supplements on blood flow and metabolite levels.
Nuances of creatine and caffeine
The researchers referenced the established body of evidence showing how caffeine acts to improve maximum strength and muscular endurance as well anaerobic performance in athletes. By attaching to adenosine receptors in the central nervous system, it diminishes sensations of pain and perceived exertion during strenuous activities and supports the sustained concentration and quick decision making required by sports activities, they noted.
Meanwhile, creatine’s role in rapidly replenishing energy-carrying molecule adenosine triphosphate (ATP) to boost short-term power output and training volume during anaerobic exercise is well documented. Beyond research showing improvements in strength, sprinting ability and muscle mass, science has increasingly focused on its potential cognitive benefits.
For this investigation, the researchers used creatine nitrate, which they noted promises the benefits of creatine monohydrate—the most widely used and supported form—and may provide the added advantage of enhanced nitric oxide production, a molecule that is “pivotal in modulating blood flow, muscle oxygenation and nutrient delivery.”
In terms of the existing research on interactions between caffeine and creatine, the study acknowledged mixed outcomes and inconclusive evidence surrounding their combined effects during resistance exercise.
Study details
The double-blind, randomized crossover trial recruited 12 resistance-trained male athletes who supplemented with creatine nitrate (5 g/day), caffeine (400 mg/day) and a combination of creatine nitrate and caffeine for seven days a piece. Each supplementation arm was separated by a seven-day washout period.
Participants provided an initial blood sample for safety analysis that included tests for key enzymes and a lipid profile. They then performed standardized resistance exercises consisting of bench and leg press repetitions and volumes at 70% 1RM as well as a Wingate anaerobic power test. Cognitive function and cardiovascular responses were also examined 45 minutes after supplementation.
“Creatine nitrate and caffeine that were co-ingested significantly enhanced cognitive function, as indicated by improved scores in the Stroop Word–Color Interference test,” the researchers reported. “Co-ingestion was more effective than caffeine alone in enhancing cognitive performance. In contrast, no significant enhancements in exercise performance were observed.”
Scott Forbes, PhD, a co-author on the study affiliated with Brandon University, noted that while surprising, the lack of effect on exercise performance in well-trained participants is most likely related to the short supplementation period, the relatively small sample size and the lack of a training program.
He did however note evidence from a previous study suggesting a small negative interaction between caffeine and creatine over time at the muscle level due to opposing effects on calcium handling.
"Caffeine increases release of calcium while creatine has been shown to increase calcium re-uptake," he said. "The way creatine and caffeine work in the brain is different than at the muscle level, and they may be synergistic."
The study called for future research to assess the effect of caffeine and creatine co-supplementation on cognitive and exercise outcomes over a longer period and across a more diverse demographic.
"The small negative effect that we saw previously also needs to be replicated," Dr. Forbes added. "If someone is concerned about every 0.1%, then perhaps take caffeine before you exercise (45 to 60 minutes before you start), and take creatine after you exercise. We know that taking creatine before and after training lead to similar resistance training adaptations."
Source: Nutrients
doi: doi.org/10.3390/nu16060766
“The Effect of Creatine Nitrate and Caffeine Individually or Combined on Exercise Performance and Cognitive Function: A Randomized, Crossover, Double-Blind, Placebo-Controlled Trial”
Authors: Gina Mabrey et al.