**2. Caffeine and its effects on metabolism**

Caffeine is the most consumed psychoactive substance in the world and is found in many different products such as coffee, tea, chocolate, soft drinks, mate, guarana powder, diuretics, stimulants, analgesics, and anti‐allergic [1].

Caffeine (1, 3, 7‐trimethylxanthine) is a stimulant of the central nervous system belonging to the group of methylxanthines [2, 7, 8]. The interaction of caffeine with the organism is difficult to research because factors such as age, presence of chronic diseases, gender, and intake of other substances such as tobacco interfere with this interaction [8].

It is believed that, with regard to pharmacokinetics, caffeine has rapid absorption, 99% absorbed within 45 minutes after its ingestion [9, 10]. It is fat‐soluble, being able to overcome all biological barriers [1, 10]. The plasma concentration in humans is achieved between15 and 120 minutes after intake [11]. In humans, doses below 10 mg/kg have half‐life by 2.5–4.5 hours and was not related difference in young and elderly subjects [1, 10].

Caffeine improves cognitive and psychomotor performance, alertness, ability to concentrate, attention, and memory; improves auditory and visual vigilance; and reduces sleepiness and fatigue [3]. Caffeine in high doses can cause tachycardia, increased gastric secretion, diuresis, increased levels of fatty acids in plasma, constriction in the cerebral vascular system, and expansion of other vessels of the body [1].

In otorhinolaryngology (ENT)/audiology, it has been linked to several symptoms and diseases, such as tinnitus, hydrops, dizziness, laryngopharynx acid reflux disease (LPRD), and as a risk factor for head and neck cancer [5, 6].

Caffeine mechanism of action for the production of these effects has not been fully elucidated. However, it is known that the caffeine molecule is chemically similar to other metabolically important compounds such as purines (adenine, guanine), adenosine, xanthine, and uric acid. Due to the structural similarity of caffeine molecule with adenosine, caffeine connects itself to adenosine A1 and A2A receptors, blocking them. Thus, adenosine cannot perform their inhibitory effect, which occurs through the release of several neurotransmitters, such as glutamate, acetylcholine, monoamines, and gamma‐aminobutyric acid [8, 12].

Other effects such as the inhibition of phosphodiesterase (cAMP enzyme inactivating) and release of intracellular calcium are also described, however, occur only at high doses of caffeine, which cannot be achieved only with the coffee intake [8, 10]. It is suggested that the mechanisms are unrelated to the central effects of caffeine [13].

Studies suggest that caffeine also has a vasoconstrictor effect, especially when binds to A2 receptors. Functional magnetic resonance demonstrated a reduction in cerebral perfusion after caffeine intake. Nonetheless, this is the predominant effect at high doses [13].

There are over a hundred years had been reported that the abrupt discontinuation of the act of drinking coffee can cause severe headaches [12, 14]. The most common symptoms of the withdrawal of caffeine are headache, fatigue, lethargy, flu‐like symptoms, and mood disorders [15]. These effects appear 12–14 hours after discontinuation of caffeine consumption and dissipate between 4 and 7 days after their occurrence [16]. The intensity of the symptoms seems to depend on the dose of caffeine that the individual usually ingest [17], although it has been reported in sporadic consumers [18]. The authors add that, despite a dose‐dependent, caffeine is not effective to alleviate the symptoms caused by one's abstinence.
