Caffeine toxicity in forensic practice: possible effects and under-appreciated sources

Musgrave, Ian; Farrington, Rachael; Hoban, Claire; Byard, Roger W.

doi:10.1007/s12024-016-9786-9

Cited by 36 publications

(24 citation statements)

References 42 publications

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“…A major issue with in vitro studies using caffeine is whether the concentrations utilised are biologically relevant [24, 45]. In the current study a significant effect was observed at levels down to 100 μM which is consistent with the IC50 (75 μM) reported for p110δ inhibition [23] and considerably lower than the plasma levels considered to be toxic (400 μM) [46, 47]. A recent study has reported human hemopoietic cells actively take up caffeine and that, in acute myeloid leukemia cells, caffeine inhibited signalling downstream from PI3K at concentrations as low as 100 μM [48].…”

Section: Discussionsupporting

confidence: 86%

Idelalisib and caffeine reduce suppression of T cell responses mediated by activated chronic lymphocytic leukemia cells

2017

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Chronic lymphocytic leukemia (CLL) is associated with T cell dysfunction. Activated CLL cells are found within the lymphoid tumor micro-environment and overcoming immuno-suppression induced by these cells may improve anti-CLL immune responses. However, the mechanisms by which activated CLL cells inhibit T cell responses, and reagents targeting such mechanisms have not been identified. Here we demonstrate that the ability of in vitro activated CLL cells to suppress T cell proliferation is not reversed by the presence of ecto-nuclease inhibitors or blockade of IL-10, PD-1 and CTLA-4 pathways. Caffeine is both an adenosine receptor antagonist and a phosphatidylinositol-3-kinase, p110δ (PI3Kδ) inhibitor and, at physiologically relevant levels, significantly reversed suppression. Significant reversal of suppression was also observed with the PI3Kδ specific inhibitor Idelalisib but not with adenosine receptor specific antagonists. Furthermore, addition of caffeine or Idelalisib to activated CLL cells significantly inhibited phosphorylation of AKT, a downstream kinase of PI3K, but did not affect CLL viability. These results suggest that caffeine, in common with Idelalisib, reduces the immuno-suppressive activity of activated CLL cells by inhibiting PI3Kδ. These findings raise the possibility that these compounds may provide a useful therapeutic adjunct by reducing immuno-suppression within the tumor micro-environment of CLL.

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Section: Discussionsupporting

confidence: 86%

Idelalisib and caffeine reduce suppression of T cell responses mediated by activated chronic lymphocytic leukemia cells

2017

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“…He had no pre-existing heart condition (Reuters News Agency, April, 2017). These two reports, coupled with statistics published in recent reviews [15] [16] [17], provide convincing evidence that caffeine can be lethal.…”

Section: [16] [17]))mentioning

confidence: 80%

“…With additional treatment, including several weeks in a psychiatric unit, this patient made a full recovery. Her circulating plasma caffeine concentrations six and eighteen hours after ingestion were 240 and 150 µg/ml [14] (note: 80 -100 µg/ml caffeine can be fatal (see refs [15]…”

Section: Resultsmentioning

confidence: 99%

Caffeine and Pressure Flow Autoregulation

Merrill¹,

Costea²,

Sharp³

2019

WJCD

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The benefits or detriments of caffeine on the human cardiovascular system have not been thoroughly studied and are still poorly understood. In a world where caffeinated beverages are evidently the adult drug of choice (e.g. coffee, energy drinks, soda, tea), investigating its effects on our bodies is of great importance. In this study, we examined the effects of caffeine, taken as a tablet, on pressure-flow autoregulation. Young adults between 18 and 21 years of age were the experimental subjects. They were instrumented to monitor systemic arterial blood pressure, peripheral blood flow, calculated peripheral vascular resistance, and the electrocardiogram during an autoregulatory maneuver in the absence and presence of caffeine. Caffeine-mediated vasoconstriction was observed as early as 15 minutes after its consumption. Sixty minutes post-caffeine, vasoconstriction was so prominent that autoregulation was abolished. This was reflected, in part, as a significant reduction in blood flow that accompanied a 3-fold increase in calculated peripheral resistance and a significant increase in systemic arterial pressure. Heart rate was unaffected by caffeine under our experimental conditions. We conclude that caffeine has the ability to inhibit significant cardiovascular properties including pressure-flow autoregulation. Even though more work is needed, the significant caffeine-mediated changes in flow, pressure and resistance during autoregulation could have serious consequences for the cardiovascular system specifically, and for one's overall health in general.

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“…Up to now, there has been limited detailed research regarding caffeine fatalities and there have been sporadic reports about it, although complete reviews have been published on the topic of caffeine [ 5 , 6 , 7 ]. The aim of this systematic review is to summarize data regarding caffeine lethal intoxications and try to identify possible categories at risk for it; data obtained from our study could support both clinicians and pathologists in identifying possible unrecognized cases and render possible a better and further comprehension of an ever-growing phenomenon.…”

Section: Introductionmentioning

confidence: 99%

Caffeine-Related Deaths: Manner of Deaths and Categories at Risk

et al. 2018

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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.

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Caffeine toxicity in forensic practice: possible effects and under-appreciated sources

Cited by 36 publications

References 42 publications

Idelalisib and caffeine reduce suppression of T cell responses mediated by activated chronic lymphocytic leukemia cells

Idelalisib and caffeine reduce suppression of T cell responses mediated by activated chronic lymphocytic leukemia cells

Caffeine and Pressure Flow Autoregulation

Caffeine-Related Deaths: Manner of Deaths and Categories at Risk

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