Most individuals adjust their caffeine intake according to the objective and subjective effects induced by the methylxanthine. However, to reach the desired effects, the quantity of caffeine consumed varies largely among individuals. It has been known for decades that the metabolism, clearance, and pharmacokinetics of caffeine is affected by many factors such as age, sex and hormones, liver disease, obesity, smoking, and diet. Caffeine also interacts with many medications. All these factors will be reviewed in the present document and discussed in light of the most recent data concerning the genetic variability affecting caffeine levels and effects at the pharmacokinetic and pharmacodynamic levels that both critically drive the level of caffeine consumption. The pharmacokinetics of caffeine are highly variable among individuals due to a polymorphism at the level of the CYP1A2 isoform of cytochrome P450, which metabolizes 95% of the caffeine ingested. Moreover there is a polymorphism at the level of another critical enzyme, N-acetyltransferase 2. At the pharmacodynamic level, there are several polymorphisms at the main brain target of caffeine, the adenosine A2A receptor or ADORA2. Genetic studies, including genome-wide association studies, identified several loci critically involved in caffeine consumption and its consequences on sleep, anxiety, and potentially in neurodegenerative and psychiatric diseases. We start reaching a better picture on how a multiplicity of biologic mechanisms seems to drive the levels of caffeine consumption, although much more knowledge is still required to understand caffeine consumption and effects on body functions.

The effects of caffeine on cognition were reviewed based on the large body of literature available on the topic. Caffeine does not usually affect performance in learning and memory tasks, although caffeine may occasionally have facilitatory or inhibi

The objective of the present research was to review the state of the art on the consequences of drinking coffee at the different levels of the gastrointestinal tract. At some steps of the digestive process, the effects of coffee consumption seem rather clear. This is the case for the stimulation of gastric acid secretion, the stimulation of biliary and pancreatic secretion, the reduction of gallstone risk, the stimulation of colic motility, and changes in the composition of gut microbiota. Other aspects are still controversial, such as the possibility for coffee to affect gastro-esophageal reflux, peptic ulcers, and intestinal inflammatory diseases. This review also includes a brief summary on the lack of association between coffee consumption and cancer of the different digestive organs, and points to the powerful protective effect of coffee against the risk of hepatocellular carcinoma. This review reports the available evidence on different topics and identifies the areas that would most benefit from additional studies.

Summary: Purpose: Administration of carisbamate during status epilepticus (SE) prevents the occurrence of motor seizures in the lithium–pilocarpine model and leads in a subpopulation of rats to spike‐and‐wave discharges characteristic of absence epilepsy. Widespread neuroprotection accompanied this change in seizure expression. To assess whether these carisbamate‐induced changes affected comorbidity, we used a large battery of behavioral tests in rats that had developed temporal lobe or absence‐like seizures.Methods: Lithium–pilocarpine or saline was administered to 60 adult rats. Carisbamate (90 mg/kg) or diazepam and saline was given 1 h after SE onset, and repeated 8 h later and twice daily over 6 more days. Rats were video‐monitored for 2 months. Subsequently, locomotor activity, anxiety, and various types of memory were assessed.Key Findings: In rats with motor seizures, treated or not with carisbamate, all features of behavior were impaired compared to controls. Rats exhibiting absence‐like seizures after carisbamate treatment behaved as controls in all paradigms tested along with widespread neuroprotection.Significance: Carisbamate treatment leading to absence‐like instead of temporal lobe seizures impressively prevented behavioral comorbidities reported by patients with epilepsy as the most disabling.

The present review is devoted to application of MRI techniques to the epileptic brain and the search for potential biomarkers of epileptogenicity and/or epileptogenesis in rodents that could be translated to the clinic. Diffusion-weighted imaging reveals very early changes in water movements. T(2)-weighted hypersignal indicates edema or gliosis within brain regions and is most often used along with histological assessment of neuronal loss. (31)P magnetic resonance spectroscopy measures the energy reserve of the tissue while (1)H spectroscopy assesses neuronal loss and mitochondrial dysfunction. (13)C spectroscopy analyzes, separately, neuronal and astrocytic metabolism and interactions between the two cell types. Finally, diffusion tensor imaging and tractography have been applied to the study of plasticity and show a good coherence with circuit changes assessed by Timm staining. The potential of these techniques as reliable biomarkers of epileptogenesis is still disputed. At the moment, one study has provided a reliable temporal evolution of the T(2) signal, predicting epileptogenesis in 100% of the cases, and further imaging approaches based on the techniques described here are still needed to identify potential early imaging biomarkers of epileptogenicity and/or epileptogenesis.