Polymorphisms, Caffeine and Sleep Disorders

Coffee is one of the most consumed drinks in the world and its consumption has doubled in 20 years. Because of the health benefits of caffeine (present in many foods and medicines), but also adverse effects, its physiological actions deserve to be better known and its use better framed.

Indeed, caffeine is the most used psychoactive substance to prevent the deterioration of the cognitive performance of night workers and soldiers in operation. Its "strategic" use is even recommended in many armies. In its sustained-release dosage form (Caffeine 300 mg), it is the only drug, increasing alertness, authorized in the French military. Caffeine also has beneficial effects on inflammatory response, muscle activity, insulin sensitivity, cardiovascular risk, weight gain, neuroprotection, chronic pain. Usual consumption of 2 to 3 coffees a day is recommended by the American Nutrition Society.

However, coffee consumption is associated with many side effects such as anxiety, sleep disorders, increased blood pressure, cardiovascular and obstetric conditions or depression. Many authors therefore recommend limiting its use. In particular, it is considered a risk factor for sleep disorders such as insomnia.

The physiological effects and sensitivity to side effects of caffeine are characterized by very high individual variability3 related to age, sex, habitual coffee consumption, smoking, but also to genetic polymorphisms. Indeed, multiple polymorphisms are associated with changes in pharmacokinetics (see Table 1) or pharmacodynamics (efficacy, see Table 2) of caffeine. Sensitivity to caffeine is associated in particular with greater vulnerability to sleep deprivation, sleep disorders and stress.n particular, polymorphisms of the adenosine receptor (ADORA) gene, a therapeutic target for caffeine, are particularly involved in the individual variability of caffeine sensitivity, side effects and consumption habits. But many other polymorphisms of genes encoding enzymes involved in metabolism or physiological effects are also associated with the individual variability of caffeine.

On the other hand, some gene polymorphisms such as the adenosine deaminase gene (ADA) which degrades caffeine and regulates intra- and extracellular concentrations, are associated with greater vulnerability to sleep deprivation, without the effects on caffeine sensitivity are known.