The caffeine in our diet comes primarily from coffee beans, but it can also be obtained in the laboratory through chemical synthesis. It is not a complex chemical compound (1,3,7-trimethylxanthine) and has the same structure in coffee, energy drinks, cocoa, tea, and tablets.

Caffeine is a powerful stimulant and can be used to increase endurance as a fat burner or nootropic compound (stimulates the nervous system).
Caffeine acts as an antagonist (adversary) of adenosine, competitively binding to receptors, and blocks its access, thereby slowing down the onset of fatigue.
Caffeine also increases the secretion of neurotransmitters such as dopamine, serotonin, epinephrine, and acetylcholine, which stimulate the sympathetic nervous system, increasing psychophysical arousal, concentration and cognitive function.
In addition, it increases the release of cellular ions and reduces the sensation of pain. By simultaneously stimulating and delaying the onset of fatigue, we can train longer and harder, at least this is a theory supported by a significant number of publications.

Elevated levels of caffeine appear in the bloodstream as early as 15 minutes after consumption, peaking in about 45-60 minutes, with a half-life of 3-4 hours (this is about the same time as the effect of caffeine). Caffeine is metabolized primarily in the liver, almost exclusively by cytochrome P450, which will be discussed later.
In general, caffeine consumption is also associated with a reduced risk of Alzheimer’s, cirrhosis and liver cancer.

Daily caffeine consumption increases the body’s tolerance to it. This means that the effect of caffeine after a while of consuming products containing it will be much less.

Caffeine works well with:

Xanthine oxidase inhibitors that increase blood levels of caffeine, which can be found in:

• Milk thistle,
• Curcumin,
• Quercetin,
• Theanine for a better and lasting stimulating effect (TC = 2: 1 combination, e.g. 500 mg theanine + 250 mg caffeine),
• Ephedrine and aspirin are both fat burners. Why does the individual body react to caffeine? One answer is the body’s adaptation to this relationship: people who drink coffee (or other caffeine-containing products) are not responding or will be less responsive than non-caffeine users (in various forms).
  This is evidenced by the following studies, which observed how caffeine added to chewing gum improved running at 40-meter intervals.
  Depending on the amount of caffeine consumed with the diet, people who typically consumed less than 40 mg of caffeine per day had better results in running tests, and this was observed in the entire group, as opposed to the group of people who consumed more than 130 mg of caffeine per day. day (i.e. at least 1 large serving of coffee).

In the footsteps of research, on the example of the work of Graham et al. [Graham. J Appl Physiol (1985) 1991. 71 (6): pp. 2292-8]. In terms of the effects of caffeine on runners, there was an increase in endurance, but the results varied widely, ranging from 5% to 87%. As in the study by Doherty et al. [Doherty. Med Sci Sports Exerc, 2002. 34 (11): pp. 1785-92], where it was found that while running (to exhaustion) on a treadmill, 9 out of 14 subjects improved their performance compared to a control sample.

This means that, despite general guidelines, not everyone will respond in the same way. This depends, among other things, on the metabolic rate of caffeine in the body, since 90-95% of caffeine is metabolized by the cytochrome P450 1A2 (CYP1A2) enzyme, encoded by the CYP1A2 gene, which is responsible for the demethylation of caffeine to paraxanthine, theophylline and theobromine. There are three variants of this gene (AA / AC / CC) that determine whether we metabolize caffeine quickly or slowly.
The second known gene associated with caffeine is ADORA2A, which is responsible for the excitability of the nervous system. So, we have a second possible answer to the question of why there is an individual answer to caffeine use – genetics.
In addition, people who slowly metabolize caffeine by consuming 3-4 servings of coffee a day, that is, a moderate amount, have an increased risk of myocardial infarction, high blood pressure, prediabetes, bladder or colon cancer, while people with the genotype that rapidly metabolizes caffeine do not show this risk, or even coffee has a protective effect on them [Guest. Medicine and science in sports and exercise, ahead of publications. DOI: 10.1249 / MSS.0000000000001596]].

What does this mean for athletes?

Some differences are also seen in athletes: people who metabolize rapidly benefit from caffeine intake much more than those who metabolize slowly, who have little or no ergogenic effect or appear ergolytic effects, i.e. worst results (!).
The results presented by Guest showed that the consumption of caffeine (4 mg / kg) by the fast metabolizers improved the ride time on a 10 km bike by 1.2 minutes, while the slower metabolizers (heterozygote AC) showed an improvement by 30 seconds. and Very Slow Metabolisers (CC) reported a 2.5 minute drop in rating.
However, further research is needed to determine the full effect of this polymorphism on the ergogenic effects of caffeine during exercise.

What’s interesting?

101 men took part in Guest’s study, 49% of whom were people who quickly metabolize caffeine, 43% were slow metabolizers (heterozygote AC) and 8% were very slow metabolizers (homozygous CC ). This means that only half of this group had a significant positive ergogenic effect, while in 8% of the group the result after drinking caffeine worsened! This is an ergolytic effect.
In other publications, these figures are repeated with a slightly smaller or larger spread, it all depends on the size of the study group. For example, in studies by Womack et al., From 2012 [J Int Soc Sports Nutr. 2012 March 15; 9 (1): 7. doi: 10.1186 / 1550-2783-9-7.], Of the 37 participants, 16 were found to be fast metabolizers and 19 were slow metabolizers of caffeine.
In a 1999 Sachse study [Br J Clin Pharmacol. Apr 1999; 47 (4): 445-449], evaluating the polymorphism of the CYP1A2 gene, it was noted that among 236 people, 46% had a gene responsible for the rapid metabolism of caffeine, while 44% had a relatively slow (AC heterozygote) and 10% of the group had slow metabolism (CC). … These results are in complete agreement with Gest’s research.

It can be assumed that only 50% of the population is predisposed to the rapid metabolism of caffeine – relatively little.

Also, I would like to mention that caffeine strongly stimulates the sympathetic nervous system, and given that a match or competition itself is also a strong stressor, the nervous system can be stimulated with all physiological consequences for a part of the body, but this will be discussed in a separate article.

What does this mean?

Despite the recommendations of various supplement organizations recommending the use of caffeine (in the amount of 2-6 mg / kg body mass ) as the best available remedy for improving athletic performance, we must be more careful when individually recommending this compound. For health reasons, you should also consider whether you should drink coffee.
Based on the studies cited, I think it’s worth going for genetically-based individualization and listening to your body / listening to your competitor’s reaction to caffeine.
Unfortunately, the commercial market does not currently offer any tests for polymorphism in the CYP1a2 gene, so it seems that “listening to your body”, that is, watching your body’s response to caffeine, would be a reasonable measure. If you see a significant difference in arousal and motor skills – then take, if you do not see such an effect – consider whether you need to take caffeine.
There are also concerns that caffeine, along with stress, can stimulate the sympathetic nervous system – then you also don’t need to take caffeine.

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Of course, more research is needed because there are still publications that question the influence of genes on the ergogenic effects of caffeine.