Does caffeine reduce the effect of creatine

Creatine and caffeine are not friends. Regular coffee intake can prevent you from getting positive results from creatine. Both enhance performance, but together these effects are inhibited. Someone asked a question about the interaction between creatine and caffeine this week. It boiled down to this: "Does caffeine have a negative effect on the function and use of creatine?". Now, I thought I had already addressed this once, but it turns out I haven't. So, there's every reason to elaborate on this now.

Creatine and Caffeine

I've written several articles about creatine (Creatine for Dummies, Creatine and Baldness, Creatine: Loading or not?). I won't delve into the benefits of creatine monohydrate here, as these have been demonstrated several times. I recently wrote extensively about caffeine, specifically its fat-burning properties. This current article mainly looks at the extent to which caffeine diminishes the effects of creatine and vice versa.

"Caffeine negates the positive effect of creatine loading"

In 1996, researchers from the Catholic University of Leuven published the results of their study (1). The title of the study already indicates their findings: "Caffeine counteracts the ergogenic action of muscle creatine loading". I mention this study first because it is often referred to by other researchers in the creatine-caffeine question. Nine healthy young men were divided into three groups. These groups received a supplement for up to 8 days.

• Group A: received creatine on days 2-7 (0.5 grams per kilogram of body weight per day divided over eight times*)
• Group B: received glucose on days 2-7 (0.5 grams per kilogram of body weight per day divided over eight times) (placebo group)
• Group C: Same as A but now + 5mg caffeine per kilogram of body weight per day on days 5, 6, and 7

It is worth noting here that this number of participants is quite low to draw conclusions for a larger population. Each group had only 3 participants, which means that individual differences play a bigger role. The researchers measured the total force the quadriceps could produce (isometric and dynamic) before and after the eight days, and how quickly it became fatigued. They also measured the amount of phosphocreatine (or "creatine phosphate") in the calves. After all, the more phosphocreatine, the more can be converted to ATP, the main fuel for the muscles. Finally, the amount of ATP itself was also measured. *We are talking about men of average 80kg and thus 40g of creatine per day. That is about double the normally recommended dosage during the loading phase, where you spread it over four doses. It is not strange that the number of intake moments is doubled as well. Results Both creatine and creatine+caffeine had no effect on ATP levels. The amount of phosphocreatine increased in both groups by the same extent, around 4-5%, but not in the placebo group. Although the amount of ATP remained the same, this could mean that both creatine and creatine+caffeine lead to a faster conversion to ATP when it becomes depleted. Regarding phosphocreatine, caffeine had no negative effect on the influence of creatine. However, when looking at the strength the quadriceps could generate, there was indeed a difference. They measured the strength during leg extension exercises. The men did three sets of three times each. Sets were of 3x30 repetitions (60 sec. rest), 4x20 (40 sec. rest), and 5x10 (20 sec. rest), with 2 minutes of rest in between. In the group that took creatine, more strength was generated than in the placebo group, especially in the first set after the 2-minute rest. This increase corresponded to the increase in phosphocreatine. In the creatine+caffeine group, however, this increase did not lead to an increase in strength, as was the case with creatine alone. The researchers had expected caffeine to have a positive effect on the effect of creatine (with the idea: "better + better = even better"):

The improvement of intermittent knee-extension torque seen after creatine was completely absent after creatine... ...We hypothesized that oral creatine intake, combined with a physiological degree of adrenergic stimulation by caffeine, might facilitate muscle creatine trapping. This, in turn, might enhance performance even further. The data demonstrate that caffeine does not improve the efficiency of oral creatine to either raise muscle PCr or enhance performance. Unexpectedly, our findings indicate that caffeine counteracts the ergogenic action of muscle -K. Vandenberghe, Catholic University of Leuven

"Opposing effects of creatine and caffeine on relaxation time"

Some of the researchers from Leuven conducted another study on creatine and caffeine six years later (2). This time, they focused mainly on 'relaxation time'. They did this mainly to explain the results from the previous study. Muscles need time and energy to contract and relax. While contraction may seem obvious, not everyone may be aware that the process of muscle relaxation also requires energy.

Furthermore, relaxation processes account for an important fraction of total energy consumption in muscles during short, repeated muscle contractions -M. van Leemputte, Catholic University of Leuven

Especially with repeated, rapid, and short-duration muscle contractions without breaks in between, shortening this relaxation time can save energy. This could then lead to extra generated strength (3,4,5). Research from 1994 had already shown that creatine loading in rats results in a decrease in relaxation time (6). The researchers from Leuven then demonstrated in 1999 that creatine also has this effect on muscle relaxation time in humans (7). Three years later, they looked at the influence of caffeine on this (2). This time, they performed an experiment with a larger group of 15 men. They again looked at the influence of creatine and caffeine on the strength of the knee extension. They also measured relaxation time and did this with a new method developed by themselves. Results The relaxation time after taking creatine decreased by 5%. That's not a huge difference, but because this process of relaxation accounts for a significant part of the energy consumption in muscles, this could still make a difference in strength. The relaxation time after taking caffeine increased by 10%. So, here you see a direct effect of caffeine. The researchers explain this difference between both effects as follows:

We speculated that caffeine, by blocking calcium release from the sarcoplasmatic reticulum, could prolong calcium uptake by the sarcoplasmatic reticulum pump, thus lengthening relaxation time. -M. van Leemputte, Catholic University of Leuven

The researchers also looked at the influence of caffeine after creatine intake. They found that the relaxation time after taking both substances was exactly the same as after taking caffeine alone. This means that caffeine neutralizes the positive effect of creatine on muscle relaxation time. This also provides an explanation for the lack of effect of caffeine in the previous study on strength.

"Creatine and caffeine inhibit each other's uptake"

There are also indications that creatine and caffeine can influence each other's uptake. Creatine is absorbed through a special transport system in the intestinal wall and from there is transported to the muscles via the bloodstream. Caffeine also has an influence on the absorption of various substances in the intestines, including calcium, vitamin D, and creatine. The exact mechanism by which caffeine does this is still unknown, but it is likely that caffeine affects the concentration of various minerals in the intestines, and thus their uptake. In an animal study from 1999, it was demonstrated that taking caffeine with creatine inhibited the absorption of creatine (8). Human research on this is lacking. Conclusion There is enough evidence to support the idea that caffeine negates the effects of creatine, although the exact mechanism is not yet clear. It is wise not to take both substances together if you want to benefit optimally from the positive effects of creatine. In addition, if you use creatine, it is wise to avoid regular use of caffeine or at least to take caffeine-containing products far from the moment of intake of creatine. In this way, you can ensure that the uptake of creatine is not hindered. It should be noted that the interactions described here only apply to caffeine and creatine monohydrate. It is unknown whether these interactions also occur with other substances that contain caffeine or creatine. I think it's not likely with the other creatine variants (e.g., kre-alkalyn, magnesium creatine chelate). References

1. Vandenberghe K, Gillis N, Van Leemputte M, Van Hecke P, Vanstapel F, Hespel P. Caffeine counteracts the ergogenic action of muscle creatine loading. J Appl Physiol. 1996 Feb;80(2):452-7. doi: 10.1152/jappl.1996.80.2.452. PMID: 8929583.
2. van Leemputte M, Vandenberghe K, Hespel P. Shortening of muscle relaxation time after creatine loading. J Appl Physiol. 1999 Oct;87(4):1474-7. doi: 10.1152/jappl.1999.87.4.1474. PMID: 10517764.
3. Greenhaff PL, Casey A, Short AH, Harris R, Soderlund K, Hultman E. Influence of oral creatine supplementation of muscle torque during repeated bouts of maximal voluntary exercise in man. Clin Sci (Lond). 1993 Sep;84(5):565-71. doi: 10.1042/cs0840565. PMID: 8504655.
4. Casey A, Constantin-Teodosiu D, Howell S, Hultman E, Greenhaff PL. Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am J Physiol. 1996 Nov;271(1 Pt 1):E31-7. doi: 10.1152/ajpendo.1996.271.1.E31. PMID: 8760083.
5. Vandebuerie F, Vanden Eynde B, Vandenberghe K, Hespel P. Effect of creatine loading on endurance capacity and sprint power in cyclists. Int J Sports Med. 1998 Jan;19(1):490-5. doi: 10.1055/s-2007-971921. PMID: 9858413.
6. Harris RC, Edwards RH, Hultman E, Nordesjö LO, Nylind B, Sahlin K. The time course of phosphorylcreatine resynthesis during recovery of the quadriceps muscle in man. Pflugers Arch. 1976 Dec 15;367(2):137-42. doi: 10.1007/BF00585265. PMID: 989618.
7. Vandenberghe K, Van Hecke P, Van Leemputte M, Vanstapel F, Hespel P. Phosphocreatine resynthesis is not affected by caffeine ingestion. Med Sci Sports Exerc. 1999 Feb;31(2):pp. 232-236. doi: 10.1097/00005768-199902000-00006. PMID: 10063822.
8. Delecluse C, Diels R, Goris M. Effect of creatine supplementation on intermittent sprint running performance in highly trained athletes. J Strength Cond Res. 2003 Nov;17(4):446-54. doi: 10.1519/1533-4287(2003)017<0446:eocsis>2.0.co;2. PMID: 14636095.