Evidence Guide · Updated 2025
Creatine and Caffeine: Does Caffeine Cancel Out Creatine?
A 1996 study by Vandenberghe et al. is frequently cited as evidence that caffeine negates creatine’s performance benefits. This single study has created lasting confusion. Here’s what the full evidence actually shows.
The 1996 Study: What It Actually Said
Vandenberghe et al. found that subjects who took creatine + caffeine simultaneously (5g creatine + 450mg caffeine daily) did not see the strength improvements seen in the creatine-only group. The proposed mechanism: caffeine increases intramuscular calcium release, opposing creatine’s effect on PCr resynthesis.
Critical caveats: the caffeine dose was very high (450mg/day, equivalent to 4+ coffees), subjects were given both simultaneously throughout the day (not separated), and the study has not been replicated in this specific high-dose design.
What Subsequent Research Shows
Multiple studies since 1996 show caffeine and creatine used together do NOT cancel out. A 2011 study (Trexler et al.) found no interference between creatine loading and moderate caffeine consumption. The most plausible conclusion from the full body of research: the interaction in Vandenberghe was specific to simultaneous very high-dose caffeine intake — not a general effect of the combination.
Practical Recommendation
You can safely combine creatine and caffeine. If you want to be conservative based on the available evidence: separate creatine and high-dose caffeine by 1–2 hours, and avoid taking both simultaneously in large doses. At normal caffeine intake (200–400mg/day from coffee or pre-workouts), the combination is fine.
Most pre-workout supplements contain both creatine and caffeine with no observed negative interactions in practice or in the majority of research.
The Bottom Line
One study (1996) with a high caffeine dose showed interference. Multiple subsequent studies show no interference at normal doses. Take creatine daily (timing flexible). Use caffeine as you normally would. If your caffeine intake is very high (450mg+ per day), separating them by an hour is a reasonable precaution.
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