Supplementation with either creatine or caffeine has consistently been shown to enhance exercise performance in most people, with these improvements thought to occur through separate physiological mechanisms.[1][2] However, some evidence suggests that caffeine may blunt the performance-enhancing effect of creatine.
For example, one study found that six days of creatine loading increased the amount of torque produced by the quadriceps during a resistance exercise protocol, but adding a single dose of 5 mg of caffeine per kg of bodyweight during the final three days of the six-day creatine-loading protocol resulted in no improvement in exercise performance.[3] Another study found that supplementation with creatine on 4–5 days per week before performing resistance exercise increased quadriceps muscle thickness, but the same dose of creatine plus 3 mg of caffeine per kg of bodyweight resulted in no increases in quadriceps muscle thickness.[4] That said, the study was significantly underpowered, limiting its ability to detect small changes over time.
One potential explanation for why caffeine may interfere with creatine’s performance-enhancing properties is the opposing effect the two substances have on muscle relaxation time. More specifically, creatine increases calcium reuptake into the sarcoplasmic reticulum (a structure in muscle cells that stores calcium) and reduces muscle relaxation time, whereas caffeine increases calcium release from the sarcoplasmic reticulum and increases muscle relaxation time.[5] Theoretically, reduced muscle relaxation time would be conducive to generating high amounts of force quickly and in rapid succession. Another potential explanation is that co-ingestion of creatine and caffeine may cause gastrointestinal distress.[6][7]
With the above said, some studies have found that after 5–6 days of creatine loading, supplementation with caffeine before an exercise test enhanced exercise performance.[8][9] Moreover, another study found no differences between supplementation with creatine, creatine plus 300 mg caffeine anhydrous, and creatine plus coffee for changes in strength, muscular endurance, or repeated sprint performance.[7] That said, although caffeine didn’t appear to blunt creatine’s effects in this study, creatine also didn’t appear to have any beneficial effects to begin with. Additionally, studies that have investigated the acute and chronic effects of supplementation with multi-ingredient preworkout supplements containing both caffeine and creatine have reported enhanced exercise performance and muscular adaptations.[10][11][12][13] However, the preworkout supplements also contained ergogenic ingredients other than creatine and caffeine (e.g., beta-alanine), which may have confounded the results.
Overall, the evidence suggesting that caffeine may blunt creatine’s performance-enhancing effects is weak and observed mainly in studies that implemented a creatine loading protocol or used high (5 mg/kg of bodyweight) doses of caffeine. This implies that this effect — if it exists at all — may not be relevant when creatine loading is not used or when lower doses of caffeine are taken. Until more research is available, it may be best to take caffeine after a creatine loading protocol has been completed, take lower (≤3 mg per kg of bodyweight) doses of caffeine when co-ingested with creatine, or simply take creatine and caffeine separately.