Autopsy report for a caffeine intoxication case and review of the current literature
01 Jan 2015-Journal of Toxicologic Pathology (Japanese Society of Toxicologic Pathology)-Vol. 28, Iss: 1, pp 33-36
TL;DR: Even though high caffeine concentrations were found in the systemic organs, no caffeine-related pathological changes were detected in the blood, urine and main organs in a fatal caffeine intoxication case.
Abstract: Caffeine (1,3,7-trimethylxanthine) is a popular mild central nervous system stimulant found in the leaves, seeds and fruits of various plants and in foodstuffs such as coffee, tea, and chocolate, among others. Caffeine is widely used and is not associated with severe side effects when consumed at relatively low doses. Although rarely observed, overdoses can occur. However, only a few fatal caffeine intoxication cases have been reported in the literature. Herein, we report the pathological examination results and information on caffeine concentrations in the blood, urine and main organs in a fatal caffeine intoxication case. Even though high caffeine concentrations were found in the systemic organs, no caffeine-related pathological changes were detected.
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TL;DR: The evidence generally supports that consumption of up to 400 mg caffeine/day in healthy adults is not associated with overt, adverse cardiovascular effects, behavioral effects, reproductive and developmental effects, acute effects, or bone status and a shift in caffeine research to focus on characterizing effects in sensitive populations is supported.
238 citations
TL;DR: Although caffeine intoxication is relatively uncommon, raising awareness about its lethal consequences could be useful for both clinicians and pathologists to identify possible unrecognized cases and prevent related severe health conditions and deaths.
Abstract: Caffeine is the most widely consumed psychoactive compound worldwide. It is mostly found in coffee, tea, energizing drinks and in some drugs. However, it has become really easy to obtain pure caffeine (powder or tablets) on the Internet markets. Mechanisms of action are dose-dependent. Serious toxicities such as seizure and cardiac arrhythmias, seen with caffeine plasma concentrations of 15 mg/L or higher, have caused poisoning or, rarely, death; otherwise concentrations of 3–6 mg/kg are considered safe. Caffeine concentrations of 80–100 mg/L are considered lethal. The aim of this systematic review, performed following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement for the identification and selection of studies, is to review fatal cases in which caffeine has been recognized as the only cause of death in order to identify potential categories at risk. A total of 92 cases have been identified. These events happened more frequently in infants, psychiatric patients, and athletes. Although caffeine intoxication is relatively uncommon, raising awareness about its lethal consequences could be useful for both clinicians and pathologists to identify possible unrecognized cases and prevent related severe health conditions and deaths.
62 citations
Additional excerpts
...…unknown 7 accidental 2 suicide 2 others Ishikawa et al. (2015) [40] Blood 154.2 mg/L Bile 852.3 mg/L Stomach 197.5 mg/L 20 F Suicide Oral (pills) Yamamoto et al. (2015) [41] 290 mg/L 18 F Suicide Oral (pills) Aknouche et al. (2017) [42] 401 mg/L 48 M Suicide Oral (pills) Magdalan et al.…...
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...(2015) [41] 290 mg/L 18 F Suicide Oral (pills)...
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TL;DR: The evidence with respect to caffeine occurrence, its persistence and remediation in light of increasing knowledge and the impact of caffeine on the environment is discussed.
Abstract: Pharmaceutical and personal care products (PPCPs) have gained attention in recent years due to their continuous discharge in natural waters. Their persistence in the environment has impacted flora, fauna and human being worldwide. One of the most common PPCPs is caffeine (1, 3, 7-trimethylxanthine) which acts as a stimulant to the central nervous system in humans and is found in nature in about 60 plant species, especially in coffee, tea and cacao plants. Here we discuss the evidence with respect to caffeine occurrence, its persistence and remediation in light of increasing knowledge and the impact of caffeine on the environment. Daily intake of caffeine around the world is found to increase due to the frequent introduction of new caffeinated beverages as well as increased consumption of coffee, tea and carbonated soft drinks, which has led to increase in its concentration in water bodies including agricultural soil. The caffeine concentration in different water system, studied by various authors is also described. Diverse effects of the use of caffeine on several organisms including humans are also briefly presented. Therefore, urgent attention for the removal of caffeine and its derivatives is the need of the hour. Various methods described in literature for caffeine degradation/removal is also presented. Another widely used technique in environmental remediation is molecular imprinting (MIP); however, only few MIPs have been demonstrated for caffeine which is also discussed. Regular monitoring can be useful to control toxic effects of caffeine. Graphical abstract.
61 citations
TL;DR: Results strongly suggested that orally administered theobromine acted as a PDE inhibitor in the brain, and it augmented the cAMP/CREB/BDNF pathways and motor learning in mice.
Abstract: Theobromine, which is a caffeine derivative, is the primary methylxanthine produced by Theobroma cacao. Theobromine works as a phosphodiesterase (PDE) inhibitor to increase intracellular cyclic adenosine monophosphate (cAMP). cAMP activates the cAMP-response element-binding protein (CREB), which is involved in a large variety of brain processes, including the induction of the brain-derived neurotrophic factor (BDNF). BDNF supports cell survival and neuronal functions, including learning and memory. Thus, cAMP/CREB/BDNF pathways play an important role in learning and memory. Here, we investigated whether orally administered theobromine could act as a PDE inhibitor centrally and affect cAMP/CREB/BDNF pathways and learning behavior in mice. The mice were divided into two groups. The control group (CN) was fed a normal diet, whereas the theobromine group (TB) was fed a diet supplemented with 0.05% theobromine for 30 days. We measured the levels of theobromine, phosphorylated vasodilator-stimulated phosphoprotein (p-VASP), phosphorylated CREB (p-CREB), and BDNF in the brain. p-VASP was used as an index of cAMP increases. Moreover, we analyzed the performance of the mice on a three-lever motor learning task. Theobromine was detectable in the brains of TB mice. The brain levels of p-VASP, p-CREB, and BDNF were higher in the TB mice compared with those in the CN mice. In addition, the TB mice performed better on the three-lever task than the CN mice did. These results strongly suggested that orally administered theobromine acted as a PDE inhibitor in the brain, and it augmented the cAMP/CREB/BDNF pathways and motor learning in mice.
40 citations
Cites background from "Autopsy report for a caffeine intox..."
...Caffeine freely 353 crosses the blood-brain barrier (BBB), and its concentration in the brain is almost the 354 same as it is in plasma [30-32]....
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TL;DR: The authors recommend that individuals avoid frequent energy drink consumption and avoid co-consumption with alcohol and increased regulatory standards should be placed in the sale of energy drinks, particularly with regard to the pediatric population.
Abstract: Context:Energy drinks are the fastest growing product in the beverage industry. However, there is concern regarding potential for adverse effects with use.Objective:To evaluate the reported adverse...
36 citations
Cites background from "Autopsy report for a caffeine intox..."
...In overdose cases, hypertension, hypotension, arrhythmia, and seizures have been reported as a result of caffeine intoxication, which may result in death.(47) Although there is published literature reviewing the effects of individual ingredients of energy drinks, there is a lack of evidence evaluating the potential adverse effects of energy drink consumption....
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References
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TL;DR: Several studies suggest that energy drinks may serve as a gateway to other forms of drug dependence, and regulatory implications concerning labeling and advertising, and the clinical implications for children and adolescents are discussed.
910 citations
TL;DR: Performance benefits attributed to caffeine include physical endurance, reduction of fatigue, and enhancing mental alertness and concentration, however, the caloric contribution of caffeine-sweetened beverages needs to be considered in the overall energy balance.
Abstract: Caffeine ranks as one of the top most commonly consumed dietary ingredients throughout the world. It is naturally found in coffee beans, cacao beans, kola nuts, guarana berries, and tea leaves including yerba mate. The total daily intake, as well as the major source of caffeine varies globally; however, coffee and tea are the 2 most prominent sources. Soft drinks are also a common source of caffeine as well as energy drinks, a category of functional beverages. Moderate caffeine consumption is considered safe and its use as a food ingredient has been approved, within certain limits, by numerous regulatory agencies around the world. Performance benefits attributed to caffeine include physical endurance, reduction of fatigue, and enhancing mental alertness and concentration. Caffeine has also been recently linked to weight loss and consequent reduction of the overall risks for developing the metabolic syndrome. However, the caloric contribution of caffeine-sweetened beverages needs to be considered in the overall energy balance. Despite all these benefits the potential negative effects of excessive caffeine intake should also be considered, particularly in children and pregnant women.
645 citations
TL;DR: Fatal caffeine overdoses in adults are relatively rare and require the ingestion of a large quantity of the drug, typically in excess of 5 g.
220 citations
TL;DR: It seems to be warranted to include caffeine in the drug-screening of forensic autopsy cases, although it is not motivated from a medical point of view to sell pure caffeine over the counter.
134 citations
TL;DR: Excessive intake of caffeine may produce arrhythmias and pronounced hypokalemia and ensuing ventricular fibrillation, and in case of counter‐shock‐resistant VF, it can be necessary to give an early loading dose of amiodarone.
Abstract: Caffeine is a natural alkaloid methylxanthine that is found in various plants such as coffee or tea. Symptoms of a severe overdose may present with hypokalemia, hyponatremia, ventricular arrhythmias, hypertension followed by hypotension, respiratory failure, seizures, rhabdomyolysis, ventricular fibrillation and finally circulatory collapse. A 21-year-old woman called for the ambulance herself soon after the ingestion of about 10,000 mg of caffeine. At the arrival of the ambulance, the patient went into cardiac arrest almost immediately. After a total resuscitation period of 34 min including seven counter-shocks and 2 mg epinephrine, the patient was stable enough to be transferred to the hospital. The patient soon went into VF again and received two more counter-shocks and 1 mg epinephrine and finally an intravenous bolus dose of 300 mg amiodarone. The initial arterial blood gas showed pH at 6.47, lactate at 33 mmol/l and potassium level at 2.3 mmol/l. Unfortunately, no blood samples for caffeine analysis were taken. Three days after hospital admission, the patient developed myoclonus, which did not respond to medical treatment. Excessive intake of caffeine may produce arrhythmias and pronounced hypokalemia and ensuing ventricular fibrillation. In case of counter-shock-resistant VF, it can be necessary to give an early loading dose of amiodarone. Furthermore, it may be beneficial to replace the potassium as early as possible. Epinephrine and buffer solutions used during resuscitation may further decrease blood potassium levels and should be administrated cautiously. Epinephrine can be replaced by other vasopressor drugs, such as vasopressin without effects on beta-receptors.
69 citations