Caffeine & Creatine: Can’t We All Just Get Along?

Caffeine is the most commonly (ab)used drug in existence. Creatine is likely the most effective legal performance supplement you’ll ever come across. It was only a matter of time before people started taking both at the exact same time. 

But that might not be the best idea.

Before you start panicking, I’m referring to acute creatine and caffeine co-ingestion probably being a bad idea; literally taking the two at the same time. Chronic use of both supplements is actually often advisable, provided you time and dose either substance appropriately. But the increasingly popular “all-in-one super preworkout supplement” that includes both of these ingredients (and more) might be burning a hole in your pocket instead of providing much additive benefits.

How Caffeine Works

First, there’s caffeine, a strong central nervous stimulant that has many psychological effects, such as improved mood/well-being (partially modulated by interactions with dopamine and other neurotransmitters), heightened arousal, and increased spontaneous movement. If you take too much of it, you’ll experience some pretty unpleasant negative side effects as well, like increased heart rate, hand tremors, cold sweats, and feelings of anxiety. 

You may also find yourself in the bathroom much more often, since caffeine not only acts as a diuretic, but can also cause gastrointestinal issues for some people.

An underlying mechanism to all of these side effects, good or bad, is caffeine’s ability to act as an antagonist to adenosine receptors. This simply means that caffeine blocks adenosine from being taken up by its intended receptors, preventing adenosine’s fatiguing effect on the nervous system. 

Wait, What’s Adenosine?

Adenosine is an organic compound produced in the body that is strongly implicated in the sleep-wake cycle. In short, adenosine levels slowly accumulate during waking hours, creating “sleep pressure”. When adenosine binds to its receptors, you begin to feel drowsy and relaxed, eventually leading to sleep.

But since nobody in today’s society has time to be tired or listen to their own body, we can simply introduce caffeine and override our instinct to hunker down at certain points in time. 

Due to its infinite availability (look out your window right now and you’ll likely see a Starbucks being built), relatively small price tag, and beneficial effects at moderate doses, it’s easy to see why a good chunk of the world is addicted to “liquid crack.” 

Unfortunately, it’s all too easy to develop tolerance to some of caffeine’s psychological effects, which are the effects most people enjoy. As little as 100 mg daily can begin this process, leaving you wanting more just to reach that level of mental satisfaction that you used to receive from a fraction of that dose. 

Can Caffeine Increase Your Gains?

As easy as it is to get hooked to the stuff, it’s even easier to make the logical inference that a lot of caffeine’s effects on the body can positively impact exercise performance. Research on endurance performance supports this claim 100% [1, 2, 3]. If you’re naive to caffeine (which is a hugely important caveat) and you’re going to be doing prolonged, low-to-mid level intensity exercise, you can greatly improve your time to exhaustion. 

For those of us who have surpassed that threshold of tolerance, the jury’s still out (but hey, it’ll still keep you awake!).

Some people have argued that caffeine imparts these benefits by altering energy utilization in the body to favor fatty acids or by increasing catecholamines like adrenaline. However, both of these ideas have been largely debunked by research. This points to caffeine’s performance-enhancing effects coming from psychological factors, such as a reduction in pain perception and increased motivation leading to people pushing harder.

It’s All In Your Head

Think about it: you take caffeine; you’re in a better mood; you’re more tolerant to pain; you do a little more work. This seems to be the extent that caffeine benefits strength training as well. As opposed to measurable benefits on time to exhaustion in endurance exercise, caffeine fails to provide a tangible increase to force production or resulting 1RMs.

When using sub-maximal loads (i.e. 60% of 1RM), caffeine may impart a marginal (~10%) increase in volume. Your set of 10 may turn into a set of 11 with the same weight, provided you’re relatively intolerant to caffeine as described earlier. This finding also supports the idea that caffeine’s mechanisms of improving performance are largely psychological, since that additional rep might have “been there” all along; the only thing that made you want to try and get it this time was the fact that you were experiencing less pain in relative terms and felt a little more “frisky.”

We can sum up caffeine’s impact on performance to be acute, psychological benefits that may allow you to push harder, but only if you’re willing to do so in the first place. Being naive to caffeine definitely helps, but that disqualifies a large chunk of the population.

How Creatine Works

On the flip side, creatine has underlying mechanisms that take time to manifest, but these changes occur at molecular and cellular levels. These changes don’t just make you think you’re stronger, these changes will make you stronger.

Creatine is a peptide composed of the amino acids arginine, glysine, and methionine. It’s not a steroid, it’s not a drug; it’s literally produced by your body and can be found in a lot of food (namely meat). However, the amount we get from food is likely too little to promote a saturation of phosphocreatine levels within muscles, which is necessary for creatine to impart its primary benefit to performance: ATP resynthesis.

When we strength train, the energy that we take in through the diet in the form of carbs and fats get broken down to form a molecule known as Adenosine Triphosphate, or ATP. During intense work, such as repeated muscle contractions, cells utilize ATP for energy by cleaving off a phosphate group. This results in ATP becoming ADP, or Adenosine Diphosphate, since one of those phosphate groups was used for energy.

This is where creatine comes to the rescue: once the overall cellular pool of phosphocreatine is “full” due to creatine supplementation, there are now more phosphate groups to be donated back to ADP to recreate ATP. In short, the major benefit of creatine supplementation is the ability to regenerate ATP faster to maintain a higher rate of energy production as opposed to not supplementing with it.

Stepping Out of the (Phosphocreatine) Pool

One of creatine’s side effects is increased cellular hydration, which many people are afraid of. The unavoidable truth is that creatine pulls water with it when absorbed into cells, kind of like how carbohydrates pull water with it when being stored as glycogen. People should probably stop complaining about this “water retention,” since a) the aesthetic impact is very mild, if even noticeable at all, and b) this cellular swelling promotes anabolism. 

When a cell is volumized, such as when it is fully hydrated, it enters an anabolic state with increased DNA synthesis and decreased protein breakdown. Glycogen synthesis can also increase under these conditions. 

Cellular swelling can also activate a specific stress response protein known as MAPk. Activation of MAPk can not only lead to increased protein synthesis, but it can also induce what’s known as “myocyte differentiation,” which can influence muscle growth via other pathways.

There has also been speculation that creatine can impart benefits on a hormonal level as well, namely by increasing Dihydrotestosterone (DHT) and the DHT:Testosterone ratio. However, as we’ve explored previously, even though some preliminary studies may have indicated that creatine can influence concentrations of these hormones, these results have never been replicated in several attempts.

All told, creatine consistently improves work capacity, strength development, and muscle growth in the literature, with lean mass gains on the order of two to three extra pounds during supplementation versus placebo.

Best of Both Worlds?

Now, combining all of these factors sounds great in principle. If you can “trick yourself” into thinking you’re stronger with caffeine, and you can actually make yourself stronger over time with creatine, why not use both? Taking it a step further, for convenience’s sake, why not take both all at once like in one of those pre-workouts plastered all over social media?

What if I told you… that taking them both at the same time renders them both ineffective?!?!

Well, I’m kind of telling you that. 

There’s no consensus amongst the literature at this point, but at least one study has noted that acute co-administration of creatine and caffeine, a method commonly seen in many pre-workouts on the market today, does not improve performance to the same extent as creatine would alone (remember: caffeine’s effects are largely psychological, so any measurable performance benefit would come via creatine supplementation in this scenario).

For instance, a study by Vandenberghe et al. showed that co-administration of creatine and caffeine “completely eliminated” the ergogenic effect of creatine. The creatine-only group experienced a 10-23% increase in dynamic torque production while the group taking both saw no benefit. It’s worth noting that this effect happened independent of a difference in the amount of creatine that was stored in the muscles, as phosphocreatine levels were similar between groups. So the contradiction has to come from something else.

In a more recent study, Pakulak et al. gave study participants a creatine pre-workout drink, a caffeine pre-workout drink, or a pre-workout drink containing both substances for six weeks. The verdict: the creatine-only group had measurably greater leg extensor muscle thickness growth than the other two groups, and enjoyed greater gains in strength, fat-free mass, and muscle thickness.

In a very real way, then, we can reasonably suggest that (over)using caffeine at the exact same time as creatine will chip away at the gains (in both size and strength) that you likely would’ve seen with just creatine alone.

But we still haven’t answered a pretty key question: how could this be?

Why Can’t We Be Friends?

Researchers at the University of North Carolina at Chapel Hill have proposed that the “wash out” effect could possibly be due to differing effects on muscle relaxation time (MRT). The supplements influence this in an opposite manner: creatine decreases MRT, which may contribute to its beneficial effects on force production; caffeine increases it. 

These researchers also posit that supplementing the two may have an additive effect on negative gastrointestinal side effects, which is absolutely plausible. Anecdotally, many people can stomach a small river of coffee, but anything more than five grams of creatine will leave them a bit queasy. If you’re sensitive to the effects of both but decide to use them in tandem before your next workout, good luck squatting!

Before you go throwing away your pre-workout supplement, know that there’s a groundbreaking way to work around this issue… just separate the doses.

Creatine and Caffeine: How to Fix the Problem

Caffeine should be saved for the pre-workout period, since you want to take advantage of any psychological benefits it may impart during your workout. Three mg/kg, or 240 mg for someone ~180 lbs (or 80kg), about 30-60 minutes before lifting should do the trick. You may even skip this part altogether if training in the evening, as it could negatively impact sleep. But if you’re a morning trainee, this would be beneficial.

Creatine should simply be saved for the post-workout period. Antonio et al. recently showed that five grams of creatine monohydrate (the only creatine worth taking, by the way) led to greater strength and body composition gains when supplemented post-workout as opposed to pre-workout. 

Following resistance training, insulin sensitivity within muscle is greatly increased. It’s advisable to include a good chunk of carbohydrate and protein at this meal to coincide with the resulting increase in muscle protein synthesis following training; these macronutrients in combination will induce a large spike in insulin that could facilitate greater uptake of creatine.

So there you have it: we still don’t know exactly what causes these supplements to contradict each other, and we still don’t know if they would show this contradicting effect in all people at all times. However, based on the evidence we do have, and the knowledge we now have of either supplement’s intended effects, we can reap the benefits of both by exercising some due diligence in relation to timing them.

If you found the information in this article intriguing, consider signing up for Menno’s Online Personal Training Course, which includes all the information presented here and much more.