The influence of caffeine on physiologic processes and exercise


Which drinks contain the most caffeine?
Caffeine is the most widely used stimulant in the world. This is because caffeine consumption is completely legal, socially acceptable, and is consumed daily by a large majority of the world population. Daily morning staples, such as coffee and tea, as well as soft drinks and energy drinks, contain caffeine. Ninety-percent of the adult population consider themselves daily coffee users, drinking on average two cups of coffee a day[1].  Much research has been conducted to determine how caffeine consumption affects one’s body systems and processes during exercise. Many studies support the findings that caffeine enhances both physical and cognitive performances. Physically, caffeine specifically improves aerobic performance—[2] extending the time that an activity can be sustained prior to fatigue. Mixed results exist as to whether caffeine significantly improves performance in resistance training[2]. Several mechanisms work on different systems of the body to produce the overall enhancement of exercise performance that caffeine causes. However, it should be noted that reliable studies exist which claim that caffeine provides no significantly increased physical or cognitive function[3]

Neuromuscular Effects

A neuromuscular mechanism that aides in causing caffeine’s ergogenic effects is it's influence on the ryanodine receptors in the sarcoplasmic reticulum of muscles[4]. The function of these receptors is to open to allow Ca2+ to flow out of the sarcoplasmic reticulum. Ca2+ facilitates the contraction of muscle fibers. Ca2+ binds to troponin, which moves tropomyosin aside so that myosin can bind to the actin myofilaments and muscle contraction can occur. Therefore, the effect that caffeine has on this system is to make Ca2+ more readily available, which allows for stronger contractions of muscles than is typical at a given level of stimulation.

Caffeine also acts on the nervous system. Specifically, it affects normal neurotransmitter release, increasing both the amount of noradrenaline (NA) and dopamine (DA) released in the brain during exercise[5]. Dopamine has widespread functions, but a few of these include influences on motivation, cognition, reward, motor control, and mood[5]. Many studies have shown that an increase in DA release results in enhanced endurance[5]. One such study showed that muscle pain perception and perceived exertion was much lower in a group that received caffeine prior to resistance training, as opposed to when those same subjects were administered a placebo on a separate date[2]. When the individuals ingested the caffeine, they performed significantly more repetitions before failure than when they were given the placebo[2]. Another study offered an explanation of the mechanism causing the reduced pain threshold. The researchers found that plasma ß-endorphin levels almost doubled after two hours of cycling with caffeine consumption, while the control group had no increase[4]. Therefore, caffeine's effect to lower pain perception is beneficial to endurance exercise performance.

Although research supports the ergogenic effects of caffeine on endurance, it has been less conclusive as to whether caffeine has the same type of effects on resistance training. Data from several studies supports an increase in resistance training performance following caffeine ingestion; however, researchers have been unable to isolate the exact physiological mechanism responsible for this. Therefore, the increased performance could potentially be due only to the decreased pain & exertion perception of the subject [as previously explained][2]

There has been evidence to show that neuromuscular performance is weaker in the morning than in the afternoon.  One study showed the positive effects of caffeine on neuromuscular performance in highly trained males [6].  The report detailed that caffeine ingested in the morning by resistance trained men allowed for the subjects to output the same amount of power as they would without caffeine in the afternoon[7].  If a therapist is working with highly trained athletes, this may be something to watch for to deter any long-term habits of relying on caffeine as there are negative effects to too much ingestion. 

Cardiopulmonary Effects

An additional performance enhancement provided to the endurance athlete by caffeine is related to the cardiopulmonary system.  When researching cross-country runners, one randomized and double-blinded study found a significant difference in the measurement of tidal volume, alveolar ventilation, and rating of perceived exertion between those who were given caffeine before performing submaximal exercise and those who were not[8].  Caffeine causes bronchodilation, which likely leads to the increase in tidal volume and alveolar ventilation.  As tidal volume and alveolar ventilation rise, an individual's respiration during exercise becomes more efficient; therefore, less exertion is required and the perceived effort needed to complete the activity is reduced[8]. Another, more recent, double-blind randomized trial also found results supporting the claim that caffeine ingestion prior to exercise lowers an individual’s rating of perceived exertion. The study also found that caffeine ingestion prior to sets of resistance exercises to fatigue had no effect on resting and peak heart rates prior to or during the bouts of exercise[9]. Despite there being strong evidence indicating caffeine's positive effects on the pulmonary system and lack of effects on heart rate, collectively the research remains inconclusive on the topics and, therefore, more experimental studies must be conducted.

One example of the conflicting evidence concerning the cardiovascular and pulmonary effects of caffeine is a study performed to specifically study the effects of Red Bull© on the systems of the body. Red Bull© contains glucuronoactone, taurine, B vitamins, and sugar in addition to caffeine. Results of the study showed significant increased arterial blood pressure (ABP), heart rate (HR), blood glucose levels, respiration rate, and respiratory flow rate (RFR) at rest and during exercise, as compared to the control group. Clearly, these physiological effects would have a negative impact on athletic performance. At various points before, during, and after energy drink consumption (500mL of Red Bull©), plasma adrenaline and noradrenaline levels were measured. The significant increase in these levels is a product of sympathetic nervous system activation. The study claimed that long term energy drink consumption could have detrimental cardiovascular and respiratory effects[10].

Metabolic Effects

One other substantial mechanism by which caffeine positively effects athletic performance is by increasing the rate that lipolysis occurs[4]. Lipolysis is the process human bodies use to break apart fats and produce ATP (our primary usable form of energy) to fuel our body. Each triglyceride (fat molecule) that is broken down produces approximately 300-400 ATP (depending on how many carbons from the specific fat are being used). The increase in fats being used to produce energy results in a decrease in carbohydrates used for that same purpose. This greatly increases efficiency because carbohydrate molecules produce far fewer ATP than triglycerides.

There are many factors in the methods of caffeine studies that cause confounded results. One factor that must be considered is the dose of caffeine administered. The many studies use different doses when investigating the effects that caffeine has on exercise. Researchers use doses of anywhere from 2-8 mg/kg, but the methods of most studies call for doses of 5-6 mg/kg[11]. Doses of 2-5 mg/kg improve athletic performance by approximately 3%, whereas doses of 5-7mg/kg improve performance by approximately 7%[11]. Another factor that often confounds results is the form of caffeine used, because other ingredients in the caffeine source cause changes in the resulting physiological effects. Other factors include diet, time and intensity of exercise tested, and length of time prior to exercise that the caffeine is administered[11]. These variables, in addition to many others, increase the complexity of research of caffeine and exercise performance.

The adverse effects of caffeine consumption in athletes who use it conservatively are minimal, if at all present. However, if the consumer is sedentary, or if the caffeine intake exceeds 7mg/kg, many negative side effects occur. In a sedentary person, caffeine interferes with the role of insulin (often resulting in hyperinsulinemia and hyperlipidemia);[10] therefore, caffeine also effects the metabolism of fats and carbohydrates[11]. Most sources of caffeine are also high in glucose, which is a combination that leads to a decline in glucose disposal[10]. Therefore, in the sedentary person, decreased glucose disposal often leads to obesity, which can cause many diseases, such as type 2 diabetes and metabolic syndromes. If caffeine intake exceeds 7mg/kg (even in the active individual), side effects such as nausea, jitters, headaches, and tachycardia present themselves. Additionally, these large doses do not improve athletic performance any more than the 7% improvement caused by doses of 5-7 mg/kg[11].

Another negative side effect that can occur from caffeine intake is it's effect on Polycystic Kidney Disease (PKD). PKD is the most common kidney disease in adults. It is an inherited disease that currently has no cure. Cysts are formed in the kidneys and grow in number and size over time. The disease can lead to many more health problems and, eventually, kidney failure[12]. There has been suggestive research that caffeine plays a role in PKD. A nucleotide known as cAMP stimulates the growth of cysts and the secretion of cyst fluid. One study showed that caffeine promotes the accumulation of cAMP in the kindeys, which leads to an increase in the size and number of cysts. The study noted that caffeine has this effect on the kidneys in only those who have PKD. If a person has PKD, they should avoid drinks such as coffee, tea, soda, or pre-workout drinks that contain a high amount of caffeine[13]. Instead, people with PKD should drink water, and can replenish their electrolytes post-workout by drinking Gatorade.


Five mechanisms of action for caffeine: [1]
1. Antagonism of adenosine
2. Increased fatty acid oxidation
3. Caffeine acts as a nonselective competitive inhibitor of the phosphodiesterase enzymes
4. Increased post-exercise muscle glycogen accumulation
5. Mobilization of intracellular calcium


  1. 1.0 1.1 Pesta DH, Angadi SS, Burtscher M, Roberts CK. The effects of caffeine, nicotine, ethanol, and tetrahydrocannabinol on exercise performance. J Nutr Metab. 2013;10(1):71. DOI:
  2. 2.0 2.1 2.2 2.3 2.4 Duncan MJ, Hankey J. The effect of a caffeinated energy drink on various psychological measures during submaximal cycling. Physiol Behav. 2013;116:60-5.
  3. Kammerer M, Jaramillo JA, García A, Calderón JC, Valbuena LH. Effects of energy drink major bioactive compounds on the performance of young adults in fitness and cognitive tests: a randomized controlled trial. J Int Soc Sports Nutr. 2014;11(44). DOI:
  4. 4.0 4.1 4.2 Tarnopolsky MA. Caffeine and endurance performance. Sports Med. 1994;18(2),109-25. DOI: 10.2165/00007256-199418020-00004
  5. 5.0 5.1 5.2 Zheng X, Takatsu S, Wang H, Hasegawa H. Acute intraperitoneal injection of caffeine improves endurance exercise performance in association with increasing brain dopamine release during exercise. Pharmacol Biochem Behav. 2014;122:136-43.
  6. Mora-Rodriguez, R, Pallares, JG, Lopez-Samanes, A, Ortega, JF, Fernandez-Elias, VE. Caffeine ingestion reverses the circadian rhythm effects on neuromuscular performance in highly resistance-trained men. PLoS ONE. 2012 Apr;7(4):1-9.
  7. Mora-Rodriguez, R, Pallares, JG, Lopez-Samanes, A, Ortega, JF, Fernandez-Elias, VE. Caffeine ingestion reverses the circadian rhythm effects on neuromuscular performance in highly resistance-trained men. PLoS ONE. 2012 Apr;7(4):1-9.
  8. 8.0 8.1 Birnbaum LJ, Herbst JD. Physiologic effects of caffeine on cross-country runners. J Strength Cond Res. 2004;18(3):963-5.
  9. Da Silva VL, Messias FR, Zanchi NE, Gerlinger-Romero F, Duncan MJ, Guimaraes-Ferreira L. Effects of acute caffeine ingestion on resistance training performance and perceptual responses during repeated sets to failure. The Journal of sports medicine and physical fitness. 2015 May;55(5):383-9. PubMed PMID: 26068323 (accessed 3 Dec 2015).
  10. 10.0 10.1 10.2 Cavka A, Stupin M, Panduric A, Plazibat A, Cosic A, Rasic L, et al. Adrenergic system activation mediates changes in cardiovascular and psychomotoric reactions in young individuals after Red Bull© energy drink consumption. Int J Endocrinol. 2015;751530. DOI:
  11. 11.0 11.1 11.2 11.3 11.4 Shearer J, Graham TE. Performance effects and metabolic consequences of caffeine and caffeinated energy drink consumption on glucose disposal. Nutr Res. 2014;72(suppl 1),121-36. DOI: 10.1111/nure.12124
  12. PKD Foundation. (2015). Learn about ADPKD. Retrieved from
  13. Belibi FA, Wallace DP, Yamaguchi T, Christensen M, Reif G, Grantham JJ. The effect of caffeine on renal epithelial cells from patients with autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2002;13,2723-9.