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Energy Water - Caffeine: evidence, dose & side-effects

Icon of calendar05/01/2022

In this article we will describe -in short- what caffeine is, what is the science behind it and what are the side-effects.

The information described in this article comes from research carried out by the (MSc) Master's students of the University of Wageningen on behalf of and in collaboration with Victus.

Caffeine (1,3,7-trimethylxanthine) is a plant alkaloid (naturally occurring organic compound with one nitrogen atom) that is commonly known for the stimulating effect on the CNS and an increase in mood, memory, alertness, physical, and cognitive performance (72–74). The primary mechanisms for cognitive stimulatory effects appear to be the blocking of the adenosine receptors and causing an increased release of dopamine, noradrenalin, and glutamate (72). Dopamine plays a role in motor control, arousal, and spatial memory function (75). Noradrenalin affects cognition by stimulating arousal, attention, and memory function (76). Glutamate affects the CNS, clinical deviations from ‘normal’ ranges of glutamate have been associated with neurodegenerative diseases (77). The ability of caffeine to block adenosine receptors can be observed at low doses, such as those contained in a single cup of coffee. Other mechanisms of action, such as the mobilization of intracellular calcium and the inhibition of phosphodiesterase(s) require higher doses of caffeine and do not influence cognitive performance but only physical performance. These higher doses are unlikely to be obtained with the common daily dietary sources of caffeine (72).

Evidence, dose, and side effects 

Caffeine has an inter-individual variation of the dose required for the stimulating effects. 99% of caffeine is absorbed in humans within 45 minutes of ingestion because caffeine has a hydro- and lipophilic nature it can rapidly cross intracellular tissue water and biological membranes including the BBB (78). The half-life of caffeine has an individual variation, but literature suggests a mean half-life of five hours. However, the elimination half-life is between 1.5-9.5 hours and, thus, influenced by their individual caffeine metabolism (78,79). A review mentioned that with 250 mg of caffeine an increased arousal, alertness, and concentration could be detected, but 500 mg was shown to increase certain side-effects such as tension, nervousness, and anxiety (80). Another study suggested that a low dose of caffeine (3mg/kg) had greater positive effects on the physical strength during intermittent exercise and improved cognitive performance than a moderate (6mg/kg) or high dose (9mg/kg) of caffeine, this study was done in physical active participants which is possibly applicable to athletes (81). Lastly, caffeine is very soluble in water, 2.17 grams per 100 mL water(82).
Caffeine is important to include in the supplement as it is safe in adequate dose and supports an increase in cognitive performance (specifically focus). However, high doses are not recommended since these can cause negative side-effects.

Caffeine is one of the most commonly used drugs in the world (Graham, 2001), it is naturally present in cacao beans, tea leaves and coffee beans. As a supplement, caffeine is available in different commercial forms (energy drinks, caffeinated beverages, pills, pre-workout and thermogenic supplements, etc.). Supplementation is popular among athletes, due to the proclaimed ergogenic benefits (Mielgo-Ayuso, Calleja-Gonzalez, et al., 2019). Although caffeine’s mechanism of action in enhancing sport performance remains elusive, the current understanding is that caffeine exerts its beneficial function through stimulation of the central nervous system. Caffeine has an antagonistic effect on adenosine receptors and subsequently promotes the release of noradrenaline, dopamine, acetylcholine and serotonin (Wilk, Filip, Krzysztofik, Maszczyk, & Zajac, 2019). The release of neurotransmitters and central nervous system arousal is proposed to be the reason for caffeine’s ergogenic effects. In addition, caffeine has been reported to increase calcium release from the sarcoplasmic reticulum and motor unit recruitment (Tarnopolsky, 2008; Bazzucchi, Felici, Montini, Figura, & Sacchetti, 2011). By doing so, a more forceful muscular contraction can be expected, which partly explains the ergogenic effects of caffeine observed in resistance exercise. Furthermore, caffeine may exert a direct effect on skeletal muscle tissue, as is suggested in both animal and human studies (Grgic et al., 2019). The popularity and suggested mechanism of action of caffeine support the idea that its consumption enhances sport performance. 

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