Caffeine & Creatine - Synergists, not Antagonists!? RCT: "Caffeine Potentiates Effects of Creatine" on Torque (+68%)

If you're looking for the extra-kick in leg workouts, the combination of caffeine and creatine may be just what you need. 
You will remember that I wrote about the results of Trexel's dissertation from 2015 and that his experimental evidence (real-world) refutes the previously postulated negative feedback of caffeine on the effect of creatine monohydrate on phosphocreatine stores (and thus logically on performance).

Against that background, I question to which extent Vandenberghe et al. (36) were right, when they postulated that the interaction between caffeine and creatine can reduce the creatine supply and the pharmacokinetics, it has also IMHO not been proven that caffeine would impair protein synthesis by depleting intracellular calcium that changes the fatigue process but damages protein synthesis.

In fact caffeine, there's more recent evidence from Moore et al. (2017) which shows that this is another theory-based hypothesis that cannot be observed in the real world of experimental science, as "caffeine administration does not impair skeletal muscle load-induced mTOR signaling, protein synthesis, or muscle hypertrophy" (Moore 2017).
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With that being said, you, as a SuppVersity reader, will be only mildly surprised to read that caffeine doesn't impair the ergogenic effects of creatine, but "potentiates the effects of creatine during physical exercise" (Jerônimo 2017).  That's at least what Jerônimo et al. (2017) observed in their latest RCT - a study that examined 16 physically active subjects 18 and 30 yrs of age who had to perform 45 reps of knee extension and flexion with a constant angular speed of 120º·sec-1 on the isokinetic dynamometer Biodex.

Immediately after the test, the same subjects began the supplementation phase for 3 days that consisted of 6 mg/kg caffeine (Caf) followed by a detox period of 5 days. After the detox period, the subjects began the supplementation with 3 g of creatine (Cr) for a period of 7 consecutive days. At the end of the 7th day the subjects continued to supplement with creatine (3 g), but also supplemented with 6 mg/kg caffeine (CrCaf) for 3 days.
Figure 1: Effect of supplementation on EMG muscle activity (Jerônimo 2017).
The scientists measured the muscle activity and torque and found significant advantages for the RMS (root mean square) of EMG and  Figure 1 shows the values from normalized RMS that were most pronounced in the caffeine-only group (4.57% Caf vs. 3.07% CrCaf vs. -17.07% Cr | yes that's a reduction in EMG with creatine only).
What else's new? Caffeine's anti-obesity effect is mediated (partly) by reduced gut-flammation: While we have known about the anti-obesity effects of caffeine for decades, we still don't know exactly how they come about. A new study adds interactions w/ cells in your gut to the list of potential mechanisms: "Caffeine indirectly suppresses lipid accumulation in 3T3-L1 adipocytes through decreasing secretion of inflammatory cytokines from Caco-2 cells" (Mitani 2017).
Now, increases in EMG are good, but, eventually, it's difficult to predict how/if they will manifest in form of increased strength or lean mass gains. Accordingly, you will be pleased to see in Figure 2 that the scientists found an increase of 4.25% in the amount of torque generated by the Caf group, an
increase of 3.45% in the Cr group, and 5.79% in the CrCaf group.
Figure 2: Adding caffeine didn't blunt, but rather increased (albeit not sign.) the torque (Jerônimo 2017).
What did not differ (significantly) between groups was the work fatigue, but a slight reduction in work fatigue was detected for the creatine + caffeine group.
Vegetarian strength athletes belong to the group of people who will probably benefit most from creatine supplementation | more
So what does the study tell us? At least in the short run/acutely, caffeine and creatine mix pretty well. With caffeine facilitating increases in EMG and creatine promoting an increase in torque (force production) their combination seems to be - that's at least what the study at hand suggests - rather optimal than detrimental.

Unfortunately, the study isn't just a small-scale acute study, the authors also failed testing the levels of creatine metabolites (to estimate creatine absorption by the tissue), which may have allowed us to refute or support the claim that a mechanistic antagonism doesn't exist | Comment!
  • Jerônimo, Diego Pereira, et al. "Caffeine Potentiates the Ergogenic Effects of Creatine." (2017).
  • Mitani, et al. "Caffeine-Stimulated Intestinal Epithelial Cells Suppress Lipid Accumulation in Adipocytes." J Nutr Sci Vitaminol 63(5) (Tokyo | 2017):331-338. doi: 10.3177/jnsv.63.331.
  • Moore, Timothy M., et al. "The effect of caffeine on skeletal muscle anabolic signaling and hypertrophy." Applied Physiology, Nutrition, and Metabolism 999 (2017): 1-9.
  • Vandenberghe, K., et al. "Caffeine counteracts the ergogenic action of muscle creatine loading." Journal of applied physiology (1996).
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