Why Doesn’t Caffeine Affect Me?

Caffeine acts as a nervous system stimulant, blocking substances that cause fatigue and stimulating the production of those that increase alertness and energy. This happens for several reasons, but primarily because of caffeine’s effect on adenosine receptors.

Our brains have a substance called adenosine that builds up throughout the day and causes fatigue by slowing down the activity of nerve cells. When we drink coffee, the caffeine blocks the adenosine receptors. As a result, we feel more alert and less tired. In addition, caffeine stimulates the production of dopamine and speeds up metabolism.

When we talk about the effects of caffeine on the body, most of the time we talk about the positive effects such as vitality, energy, alertness. However, we should not forget that caffeine can also increase anxiety.

There are also people who fall asleep after drinking a cup of coffee or feel no change at all. In this case, the effect of coffee on the body is more subtle for a number of reasons. There are two main scientifically proven reasons why you may not feel the effects of caffeine: genetics and tolerance.

Genetics

One of the most important factors in caffeine sensitivity is your genetics. Two genes, in particular, play a crucial role: CYP1A2 and ADORA2A. More than 95% of caffeine is metabolized by CYP1A2. Caffeine is absorbed through the intestines within 30 to 45 minutes of consumption. Once absorbed, caffeine is metabolized in the liver by the enzyme CYP1A2 into three primary metabolites:

• Paraxanthine (up to 80% of caffeine metabolism)
• Theobromine
• Theophylline

People have different versions of the CYP1A2 gene, which can either speed up or slow down the metabolism of caffeine. If you metabolize caffeine quickly, it will leave your system faster, reducing its stimulating effects.

Average handgrip strength by caffeine dose and CYP1A2 genotype / ResearchGate

ADORA2A affects how sensitive your brain’s adenosine receptors are to caffeine. Variations in ADORA2A can make these receptors less responsive to caffeine, reducing its ability to keep you awake.

Effect of caffeine on anxiety as a function of ADORA2A genotype group / ResearchGate

Caffeine tolerance

If you drink coffee regularly, your body may have developed a tolerance to caffeine. Over time, your brain may adapt by increasing the number of adenosine receptors, which means it takes more caffeine to block the same amount of adenosine and achieve the desired alertness.

You can manage tolerance by cycling your caffeine intake, which involves periods of high intake followed by periods of low or no intake to reset tolerance levels. Limiting your daily caffeine intake can also help maintain its effectiveness and prevent significant tolerance development.

The paraxanthine and caffeine concentrations at the respective time points and the dynamics of cerebral responses on the laboratory day (day 10) in daily caffeine and caffeine deprivation conditions, respectively / Frontiers in Nutrition

With daily consumption, caffeine excretion may slow and the major metabolite, paraxanthine, may accumulate. The body does not have time to restore brain responses even after 36 hours of caffeine abstinence.