By Eric Trexler, PhD
Eric Trexler is a Lecturing Fellow at Duke University where he teaches and conducts research related to exercise and nutrition. He is a former strength coach and pro natural bodybuilder who has published over 60 peer-reviewed papers about getting bigger, stronger, leaner, and healthier.
Caffeine is everywhere. It’s the most frequently consumed psychoactive substance on the planet, it’s regularly consumed by over 80% of American adults, and in some cultures average daily intake exceeds 400 mg/day. It’s been used for thousands of years across numerous cultures. It was briefly a banned substance, then made a remarkable comeback. All in all, caffeine has had an interesting life, and it’s currently riding high on a wave of popularity.
Figure 1: Average daily caffeine intake by country
Caption: Image source: https://journals.lww.com/co-lipidology/fulltext/2007/02000/coffee,_caffeine,_and_coronary_heart_disease.5.aspx
Published research framed caffeinated beverages (namely coffee) as harmful in the 1980s, but research flipped that perspective entirely by the early 2000s. Over the last several decades, parallel research has linked pre-exercise caffeine with improved performance. Unlike most supplements, caffeine has been shown to improve a wide range of performance types including aerobic endurance, sprints, strength, muscular endurance, and power. It also improves subjective focus and perceived energy during workouts while reducing perceived exertion – no wonder it’s the primary ingredient in just about every pre-workout supplement on the market.
Having said that, caffeine research is constantly evolving. I’ve published research papers and textbook chapters about caffeine and have generally framed it in a categorically positive light. But in recent years, a few key findings have caused me to revise some of my conclusions and add some major caveats to others. So, let’s dig into the newest caffeine research to discuss caffeine’s pros, cons, and most justifiable use cases.
Who Stands to Benefit From Pre-Workout Caffeine?
Caffeine has been studied for over a century, yet its exact performance-enhancing mechanisms remain debated. Early theories focused on peripheral effects, such as catecholamine release and increased glycolytic flux, but these explanations fail to consistently account for caffeine’s ergogenic impact. Similarly, the idea that caffeine improves performance by enhancing fat oxidation and sparing glycogen is incomplete, particularly for high-intensity strength or power exercise where glycogen isn’t the limiting factor. Another proposed mechanism—boosting sodium/potassium pump activity—has shown inconsistent evidence and doesn’t appear to drive strength outcomes.
Current consensus points to caffeine’s action on the central nervous system, particularly its antagonism of adenosine receptors (A1 and A2A). By blocking adenosine, caffeine reduces perceived exertion, increases alertness, and helps sustain motor unit firing, all of which support force production and fatigue resistance. Importantly, research on electrically stimulated muscle contractions in quadraplegic patients—where central nervous system involvement is minimized—shows caffeine still enhances muscular endurance, suggesting additional peripheral mechanisms, likely related to increased calcium release within muscle. In short, while adenosine antagonism is the primary mechanism, a secondary role for muscle calcium handling likely contributes, making caffeine’s benefits applicable to both endurance and strength exercise.
Figure 2: How caffeine works
That’s all great, but there’s one problem: caffeine metabolism and adenosine receptor production vary based on your genes. The CYP1A2 gene codes for the CYP1A2 enzyme, which is responsible for metabolizing ~95% of caffeine in the liver. The ADORA2A gene codes for the adenosine A2A receptor. Changes in wakefulness, pain perception, and a variety of other physiological effects result from caffeine blocking this receptor. Intuitively, researchers have wondered whether or not these specific genes ultimately impact caffeine’s performance-enhancing effects. If so, then caffeine would only be viewed as an effective supplement for a percentage of the broader population.
A 2020 review identified 11 studies investigating the effect of CYP1A2 genotype on caffeine’s ergogenic effect during aerobic exercise. Of those 11 studies, only two reported a significant effect, with both indicating that carriers of the “C” allele had smaller performance improvements in cycling time trials of fairly long durations (10-40km). Eight studies investigated “high-intensity” exercise, such as strength, muscular endurance, sprinting, jumping tests, agility tests, and sport-specific exercise tests. Of those eight studies, only two reported a significant effect. Both reported very modest differences indicating that carriers of the “C” allele had slightly smaller performance improvements in some of the performance outcomes measured. Overall, it seems that having one or more C alleles for the CYP1A2 gene may slightly attenuate the ergogenic effect of caffeine, but it doesn’t mean that carriers of the C allele will have no ergogenic response at all. In addition, the effects reported in this research are small and inconsistent.
For ADORA2A, there is far less literature available. A very small pilot study sampling 12 women found that caffeine significantly improved 10-minute cycling time trial performance in the group of women with the TT genotype (n = 6), but not in the group of C allele carriers (n = 6). A separate study by Carswell et al. (8) investigated the impact of CYP1A2 and ADORA2A genotypes on 15-minute cycling time trial performance. Caffeine significantly enhanced performance in all genotypes by about 6-8%, with very similar values among all CYP1A2 and ADORA2A genotypes. Grgic and colleagues carried out a study in a sample that only included carriers of the C allele for the ADORA2A gene (9). While this impaired their ability to compare effects between genotypes, it allowed them to determine whether or not the C allele prevented participants from enjoying an ergogenic effect from caffeine supplementation. They analyzed 25 different performance variables including a wide range of strength, sprint, jump, and muscular endurance tests. Caffeine significantly improved performance in 21 of the 25 tests, and the size of these improvements was very consistent with the broader caffeine literature with mixed-genotype samples. Based on the totality of the evidence, carriers of the “C” allele still seem to enjoy performance benefits, and it’s too early to conclusively suggest that they experience smaller effects than individuals without the “C” allele.
Overall, the idea that CYP1A2 or ADORA2A genotypes have a large, consistent impact on caffeine’s ergogenic effects seems to be losing steam – but that doesn’t mean everyone experiences the same effects from caffeine. There are a huge number of factors that may alter caffeine metabolism, such as smoking, estrogen levels, menstrual cycle phase, oral contraceptive use, obesity, a wide range of prescription drugs, habitual caffeine consumption, and the consumption of alcohol, flavonoids, apiaceous vegetables, grapefruit juice, brassica vegetables, and charred meat. But even beyond these inter-individual differences, recent research surprisingly shows us that the performance effects of caffeine can be very hit-or-miss, even among people who sometimes experience
positive effects.
Variability of Performance Benefits
In a 2022 study by Tamilio and colleagues, 22 male rugby players completed a series of exercise tests under caffeine and placebo conditions—three sessions each, for a total of six sessions. This setup essentially repeated the same experiment three times in the same group, allowing the researchers to assess how consistent the caffeine effect was within individuals. On average, caffeine improved performance for countermovement jump, drop jump, and repetitions to failure. But here’s the kicker: even though the protocol, dose, and timing were identical across visits, the effect sizes ranged from trivial to large. So while caffeine “worked” overall, the day-to-day response was highly variable, even within the same person doing the same test.
That variability could stem from a bunch of things: random measurement error, daily fluctuations in fatigue or motivation, or just plain old biological noise. It’s hard to say exactly. But this kind of variability means we need to be cautious when interpreting caffeine studies and when interpreting our personal response to caffeine. Unfortunately the response we get on Tuesday isn’t necessarily the response we can expect on Thursday. And, more importantly, we have to consider the long-term effects of caffeine use if we really want to predict how much performance enhancement we can realistically expect to observe.
Duration of Caffeine Use
The first time you had a tall cup of coffee, you might have felt invincible (or uncomfortably jittery). But have a few cups daily and you’ll find that those amplified responses become increasingly muted over time – this is called habituation, and it shows how our body “gets used to” caffeine over time, ultimately dulling our responsiveness for certain outcomes. Over time our massive changes in wakefulness, heart rate, and blood pressure may fade, but do we retain our performance benefits?
You’ll find a lot of conflicting information on this topic, mostly because there are two very different ways to approach the question. One method is to invite people to participate in a study and ask them how much caffeine they typically use. With this approach, it’s very clear that self-reported caffeine users still get performance benefits in response to pre-exercise caffeine injection. However, this approach relies heavily on self-reported assessments of caffeine dose, frequency, and regularity.
A more straightforward approach involves actually giving people a standardized caffeine dose daily for weeks on end and measuring their performance effects along the way. Very few studies take this approach for obvious reasons – it involves a lot more time, labor, and money. But it’s the only way to truly tackle the question head-on.
A 2019 study by Lara and colleagues studied the ergogenic effect of pre-exercise caffeine supplementation (3mg/kg) over a 20-day period. The results generally suggested that the magnitude of caffeine’s ergogenic effect decreased with repeated use. However, the relative degree of effect size reduction varied among the different performance outcomes measured, and an effect size getting smaller is not the same as an effect size disappearing entirely. It’s also unclear if the effect sizes were on a trajectory involving continuous decreases over time, or if the effect size reductions had effectively plateaued at a lower (but still non-zero) magnitude of performance enhancement.
Figure 3: Ergogenic effect of caffeine can shrink (but not disappear) over time
Overall, research seems to suggest that caffeine’s performance-enhancing effect shrinks with daily consumption, but doesn’t fall all the way to zero. But here’s another important question: does it matter?
We don’t really train for the sake of having good workouts. We train to induce training adaptations – to become bigger, faster, stronger, and so on. It doesn’t really matter if regular caffeine use still provides a tiny performance enhancement in the gym if that enhancement fails to translate to better gains over time. Crazy as it sounds, there are surprisingly few studies that actually measure this directly.
One such study, published in 2021, randomly assigned 16 resistance-trained, caffeine-naive participants to ingest caffeine (3mg/kg) or a placebo prior to workouts over the course of a four-week bench press training program (12 total workouts). The training program involved sets of 8-10 repetitions using 60-70% of 1RM and was designed to maximize increases in peak velocity and power using intermediate loads. The caffeine group made slightly better improvements in bar velocity and peak power across a wide range of loads from 10% of 1RM to 100% of 1RM, and they made very slightly larger increases in bench 1RM. However, these effects were not large enough or consistent enough to be considered statistically significant. More research is needed, but the best available evidence suggests that habitual pre-workout consumption of caffeine may have effects ranging from neutral to small (but positive).
Figure 4: Effects of regular caffeine supplementation on strength gains over time
Timing of Caffeine
On one hand, caffeine timing is simple. Research shows that taking caffeine 30-60 minutes before exercise can improve performance across a wide range of physical tasks. Caffeine also stays in your system for several hours, so there’s no harm done if you have to take it 90 or even 120 minutes beforehand. However, there’s also a pretty major drawback to caffeine’s slow clearance.
Caffeine already has a half-life of around 5-6 hours, on average. In other words, it already takes a long time to leave your system, which can pose a major threat to the quantity and quality of your sleep. A common myth is that caffeine only messes with your sleep if you consume it late in the evening. In reality, recent research suggests you’d need to take any substantial dose of caffeine (>200 mg) at least 13 hours before bed to confidently avoid sleep disruption. It’s hard to overstate how important this is – caffeine’s potential benefits on training adaptations are tiny, whereas sleep disruption can lead to impaired recovery, impaired performance, loss of lean mass, impaired appetite regulation, and difficulty losing fat.
If you’re still not sold on restricting your caffeine use to the morning hours, another line of research might win you over. A group of researchers investigated the ergogenic potential of three different caffeine doses (3 mg/kg, 6 mg/kg, or a 0 mg/kg placebo) at two separate times of day (morning versus evening) in female handball athletes. Caffeine was most effective at improving performance when ingested in the morning, and 6 mg/kg was generally more effective than 3 mg/kg. Evening caffeine ingestion did not significantly improve performance and was associated with more side effects, especially when the higher dose (6 mg/kg) was ingested. If you’re keeping score at home, caffeine in the late afternoon or evening is losing across the board: no performance improvement, greater side effects, and impaired sleep. Not exactly a great sales pitch for a hypercaffeinated preworkout formula.
What About Novel Forms of Caffeine or Caffeine Alternatives?
A novel trend in the caffeine world involves making attempts to extend caffeine’s effects. For example, some studies have investigated the use of threacrine instead of caffeine – theacrine has similar effects on the body, but a much slower half-life. This means it enters the system a bit more slowly but circulating levels in the bloodstream remain higher for longer. Similarly, a fairly new addition to the supplement market includes dual-release or triple-release caffeine products that offer an immediate, sustained, and/or delayed form of caffeine. The goal of these products is to provide an initial elevation of circulating caffeine, but to sustain that elevation for a more prolonged period of time than normal caffeine.
These sound like cool, creative ways to make a good thing better, but I’m not into it. In my opinion, this is making a flawed (but useful) thing worse for most lifters and athletes. As I mentioned earlier, caffeine has a long half-life and lingers in your system for a while – too long, in my opinion. As a result, large caffeine doses should be restricted to the morning hours. After all, caffeine’s benefits are very small in magnitude – the modest upsides of pre-workout caffeine are dramatically outweighed by the downsides of sleep disruption.
If I had it my way, I’d fork over extra money for a version of caffeine with a dramatically shortened half-life, but certainly not a dramatically extended half-life. But there are, of course, exceptions. When you’re trying to use caffeine to improve performance in a 60-minute workout, a shorter half-life is clearly preferable. But if you’re doing an all-day event requiring peak performance across a several-hour window or completing a multi-hour military mission in an underslept state, those are clearly scenarios where a longer half-life would be clutch.
Conclusions
Plenty of evidence suggests that caffeine, dosed at 3-6 mg/kg of body weight and taken 30-60 minutes before exercise, improves a wide range of performance outcomes including endurance, power, and strength. However, it’s very important to contextualize the performance-enhancing potential of caffeine. Its effects on performance are pretty variable, whether you’re comparing between individuals or comparing day-to-day effects for a single person. Its benefits appear to shrink (but not disappear entirely) when you lean on it daily. Its acute benefits (observed directly after consumption) may help you get a better workout, but its chronic impact on actual training adaptations (i.e., strength and muscle gains) are smaller than you might expect. In addition, it only appears to work when taken in the morning, and consuming it too late in the day can increase the likelihood of side effects and sleep impairment.
With this in mind, pre-workout caffeine consumption makes the most sense when you’re trying to: 1) facilitate the transition from afternoon or evening training to morning training, 2) preserve performance in a training session or competition occurring in an underslept state, or 3) occasionally boost your subjective enjoyment of training sessions. This is quite different from the common assumption that caffeine will provide a perpetual, reliable enhancement of performance whenever you happen to use it. Caffeine isn’t useless, but its effects are commonly overhyped and its drawbacks are often overlooked.
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Eric Trexler, PhD
IG: @trexlerfitness
