Supplement Review: Caffeine
Caffeine has been studied as far back as 1907 as an ergogenic aid for sports performance. The ergogenic effects on sports performance have been thoroughly observed in endurance athletes (2,5,6,8-10,12,14) and more recent studies have shown improvements on several anaerobic performance measures as well (1,3,4,7,9,13,16). There are several plausible mechanisms that attempt to identify caffeine’s impact on improved endurance, strength, and power through increases in lipolysis, excitatory neurotransmitter release, and/or the maintenance of the motor neurons resting membrane potential. Certain genetic variants may also impact the ergogenic effects and side-effects elicited from caffeine supplementation. In order to make practical recommendations on caffeine supplementation for athletes, many variables need to be taken into account. A better understanding of caffeine’s mechanisms of action as well as several potential genetic predispositions and their corresponding phenotypes will allow for more precise caffeine recommendations to be made
The use of caffeine on aerobic performance and muscular endurance is well documented (2,5,6,8-10,12,14). Endurance performance has been evaluated in several ways, either through time-to-exhaustion (2) or time-trial protocols (6). Time-to-exhaustion studies have participants exercising at a set submaximal intensity until voluntary fatigue occurs. Bell and Mclellan observed the effects of caffeine ingestion on repeated exhaustive performance in nine male athletes and found that 5mg/kg of caffeine was able to increase time-to-exhaustion by 24.9 +/- 10.2 minutes in the morning session and 21.5 +/- minutes in the evening session. Bell and Mclellan’s results are consistent with similar studies showing caffeine ingestion is able to improve endurance performance through anti-fatigue mechanisms (5,8,10). However, time-to-exhaustion protocols do not accurately simulate athletic competition, as Ganio et al states in their systematic review; most sporting events are focused on performance in a set amount of time or are more time trial based (6). Time-to-exhaustion protocols are also highly susceptible to type I errors as minute changes in overall power output, which may not be significant in a time trial protocol, can elicit very large changes in time-to-exhaustion performance, rendering false positives (6). Ganio et al focused their systematic review on caffeine’s effect on studies using time trial protocols. Regardless of when caffeine was ingested, on average, caffeine improved performance by 3.2 +/- 4.3% over the placebo (6). Caffeine ingested before time-trial protocols elicited an improvement of 2.3 +/- 3.2% compared to 4.3 +/- 5.3% when caffeine was ingested prior and during testing (6). Out of the 33 studies that were included in the time-trial systematic review, 30 observed enhanced performance with caffeine ingestion and 15 of those were noted as being statistically significant (6). Endurance improvements were observed with caffeine dosages of greater than 3mg/kg and no changes in improvement were observed with increasing dosages up to 9mg/kg (6).
Studies involving high-intensity exercise also show improvements on several anaerobic measures after caffeine ingestion (7,9,13,16). In a recent systematic review and meta-analysis by Grgic et al, caffeine ingestion was shown to improve anaerobic measures of strength and power. 10 studies were reviewed for their anaerobic strength measures via 1RM testing. Upper body strength was found to be significantly improved following caffeine ingestion, while there was little to no effect on lower body strength (9). Grgic et al’s review of caffeine’s impact on anaerobic strength conflicts with previous theories that suggested caffeine would have a greater effect on larger muscles, which are mainly located in the lower body (9). An additional 10 studies were reviewed for anaerobic power, measured mainly via vertical jump and one using a Wingate test. Similar to strength, anaerobic power measures were improved after the ingestion of caffeine. Acute caffeine suggestion prior to vertical jump tests was reported to having as significant an impact on performance as 4 weeks of plyometric training (9). Increases in strength and power translate to increased performance in competition in many sporting events, and caffeine ingestion prior will most likely enhance performance.
While previous systematic reviews state that caffeine’s ergogenic effects on endurance did not vary between modes of delivery (6), Grgic’s review found significant increases in strength and power when caffeine was ingested via capsules (9). Habitual caffeine use may also impact the degree to which caffeine acts as an ergogenic aid. Bell and Mclellan observed greater improvements in performance for non-users versus habitual users (2). Further studies have reported enhanced performance in subjects that abstained from caffeine use 2-4 days prior to testing (6).
Caffeine, 1,3,7-trimethylxanthine, is a member of the methylxanthine family and is metabolized in the liver by cytochrome P-450 (8,14,18). Theobromine, paraxanthine, and theophylline are metabolites of coffee and are responsible for its downstream ergogenic effects (8,14). Theobromine induces vasodilation, Theophylline stimulates the adrenal medulla to release the excitatory neurotransmitter epinephrine, and paraxanthine has been associated with increases in the mobilization of free fatty acids (1,8).
Adenosine acts as a key regulator for a number of processes and has inhibitory effects on the central nervous system making it harder for the body to recruit muscle (3). However, this inhibitory effect of adenosine may be alleviated through caffeine ingestion. Caffeine and its metabolite theophylline can antagonistically bind to adenosine receptors, preventing an influx of inhibitory signals sent via adenosine binding (8). Increases in excitatory neurotransmitters from caffeine ingestion will allow for more ligand gated ion channels on the synapse of motor neurons to be activated, reducing the time it takes for an action potential to be generated as more calcium and sodium will enter the soma to depolarize the membrane. Within one hour of caffeine ingestion elevated plasma epinephrine concentrations are observed both at rest and during exercise (8). Caffeine could also impact the threshold potential for muscle contraction via translocation of calcium ions between plasma and the sarcoplasmic reticulum, allowing for greater stimulus of ryanodine receptors on the sarcoplasmic reticulum (8).
Caffeine may improve aerobic performance via increased calcium build-up in the cisternae of sarcoplasmic reticulum and increase plasma epinephrine, both of which increase the activity of phosphorylase a, an enzyme that breaks down glycogen into glucose to be used as fuel for glycolysis. Other plausible mechanisms that may account for the anti-fatigue properties of caffeine focus on the attenuation of high extracellular potassium concentrations and also increasing intracellular calcium concentrations. High extracellular potassium concentrations are often observed after high-intensity exercise and correspond with reduced excitability of neurons, lower conduction velocities, and increased fatigue (3). Caffeine may positively impact resting membrane potentials by increasing circulating catecholamine concentrations that increase the activity of sodium-potassium pumps (3). Maintaining resting membrane potentials allow for excitatory neurotransmitters to be more effective at generating action potentials that result in more efficient muscle contractions, thus increasing endurance. Through these mechanisms, caffeine and its metabolites can enhance sports performance by increasing power output, decreasing the rate of perceived exhaustion, and delaying fatigue.
From Skinner, J. and D. Morgan. Aspects of anaerobic performance. In Limits of Human Performance. Champaign: Human Kinetics Publishers, 1984, pp. 31-44
As the intensity of exercise approaches an individuals vo2max and the duration decreases our body begins to progressively use more of our anaerobic system to fuel performance. Our anaerobic system runs on ATP provided from high energy phosphates and from the breakdown of glucose and glycogen that our body has stored from ingested foods. High-intensity exercise demands our muscles to produce high power outputs. The principle of orderly recruitment staes that our body will recruit just enough muscle to satisfy the demand in external force. For maximum intensity exercises like 1RM’s, your body will recruit all of your fast-twitch muscle fibers in order to produce the most amount of power and strength, while only lifting 50% of your 1RM will recruit just enough muscle to lift that load. These fast twitch fibers are very glycolytic and run on ATP supplied mainly from anaerobic glycolysis during high intensity exercise. The recruitment of muscle fibers begins with the generation of action potentials at the axon hillock of motor neurons. Action potentials will only be sent if the resting membrane potential along the axon hillock is depolarized by 15-20 millivolts in which a threshold is surpassed allowing for a rapid influx of sodium into the membrane. Excitatory neurotransmitters like epinephrine or glutamate will bind to receptors on the membrane of the motor neuron, activating ion channels that permit an influx of calcium and sodium into the soma. This influx of cations elicits small depolarizations along the membrane that can build up to meet the threshold potential needed to send an action potential. The smaller the cell body of the motor neuron the quicker this threshold will be met to activate its muscle fibers. Your body will progressively excite more motor neurons until enough muscle fibers are recruited to match the demand in force. Increases in plasma excitatory neurotransmitters from caffeine ingestion may help initiate more action potentials and recruit and contract more muscle fibers faster and with greater force, as research has shown (1,8,9). Caffeine and its metabolites may also help maintain resting membrane potentials by increasing the activity of ATPase sodium-potassium pumps (1,8,9).
Powers et al Exercise Physiology: Theory and application to fitness and performance, Chapter 5: Cell Signaling and the Hormonal Responses to Exercise
Intense bouts of exercise that last less than a minute will require much more of the anaerobic system, while exercise that persists longer than 10 minutes almost entirely relies on the aerobic system to supply ATP to the working muscle. Increasing the duration of exercise is associated with rises in epinephrine, glucagon, cortisol, and growth hormone concentrations, all of which signal the body for glycogen and fat breakdown in order to generate ATP. Fat is a much more abundant fuel source and produces more ATP than any other macronutrient. However, fat takes a longer time to be metabolized and fed into the Krebs cycle as Acetyl CoA. Caffeine ingestion has been proposed to enhance endurance performance by increasing fat breakdown and sparing muscle glycogen, however recent systematic reviews did not report any significant changes on muscle glycogen levels (1). Caffeine may enhance fat breakdown via elevated plasma epinephrine levels. Epinephrine can bind to G-protein coupled receptors on the membrane of adipose tissue and increase the activity of hormone sensitive lipase, the enzyme primarily responsible for the breakdown of triglycerides into free fatty acids to be used by our aerobic system. Caffeine ingestion prior to exercise may increase lipolysis by elevating plasma epinephrine levels to a higher degree. This may be a mechanism by which caffeine improves time-to-exhaustion performance.
Although the literature shows that caffeine ingestion can improve exercise performance, and on average does, numerous studies also show that some subjects do not receive any performance enhancing effects with caffeine. Womack et al were the first to test whether genetics may explain the differences observed on the ergogenic effects of caffeine between subjects. They identified a single nucleotide polymorphism, rs762551, on the CYP1A2 gene that codes for cytochrome P450. As mentioned previously, cytochrome P450 is located in the liver and is responsible for the metabolism of caffeine. Caffeine ingestion of 6mg/kg prior to a 40-kilometer time trial cycle race revealed that subjects expressing the homozygous A allele for this single nucleotide polymorphism responded more favorably to the caffeine treatment than subjects expressing the C allele (18). These findings suggest that individuals with homozygous A alleles can metabolize caffeine much quicker and will elicit greater ergogenic benefits from caffeine (18). Another single nucleotide polymorphism has been identified that may possibly impact a subject’s acute response to caffeine. Located on ADORA2A, a gene coding for adenosine receptors, the snp rs5751876 may determine if an individual will elicit any beneficial or detrimental effects from caffeine. TT homozygotes for this gene were able to utilize caffeine to enhance performance, while those expressing the C allele did not benefit as much (14). This snp was also associated with increased anxiety following caffeine ingestion for TT carriers and reduction in sleep quality for C allele carriers (14).
Genetic and non-genetic factors influencing caffeine ingestion decisions (14)
Practical guidelines for caffeine supplementation in order to enhance athletic performance should take these possible genetic factors into account. Since most athletes will not be able to be genotyped in order to identify which allele configuration they express, each individual should use trial and error to determine what the best dosage of caffeine is for them personally. Even for habitual users, abstaining from caffeine for 7 days is recommended in order to return caffeine sensitivity back to baseline levels (6). Once the athlete has returned to baseline sensitivity, 3-6 mg/kg of should be ingested one hour prior to exercise. If the athlete feels increasingly anxious with increasing amount of caffeine, they may express the homozygous TT genotype for adenosine receptors, this suggests they are more sensitive to the ergogenic effects of caffeine and could possibly benefit from lower doses (14). If the subject finds sleep is easily disrupted with even minimal ingested amounts of caffeine, the C allele for ADORA2A may be present, and caffeine use is recommended only when the need for performance enhancement outweighs the need for quality sleep that night (14). If the athlete feels that caffeine ingestion significantly improves their performance, they may be fast metabolizers of caffeine, likely containing the homozygous A alleles for cytochrome P450 (14,18). These individuals may benefit from following general guidelines for caffeine supplementation recommending 3-6mg/kg be ingested 30-60 minutes prior to exercise. If little to no effect on exercise performance is experienced following these general guidelines, they may contain the C allele and will metabolize caffeine much slower (14,18). These individuals may still benefit from caffeine’s ergogenic effects if ingested more than an hour before the start of exercise and/or at higher dosages (14). Performance enhancement may also be modulated by its mode of delivery. Caffeine administered via capsule form was shown to elicit greater improvements on strength and power (9). Therefore it may be beneficial to use caffeine capsules prior to exercise like weight lifting or high intensity sports that are enhanced by increased force production.
Studies have consistently shown that caffeine ingestion is able to improve exercise performance in a majority of subjects. These improvements in performance have been observed for both aerobic and anaerobic measures (1-13,16). However, some individuals may contain specific genetic variants that could require differences in dosing or time ingested prior to exercise in order to elicit similar performance enhancing effects (14, 18). All in all, the literature on the ergogenic effects of caffeine show that caffeine ingestion in the right amount and at the right time may enhance performance in nearly all subjects, no matter the duration and intensity of exercise.
References:
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