Posted by: Chris Maloney | March 27, 2012

One Energy Drink Keeps You Awake, Will Drinking Two Kill You?

Caffeine has a significant effect on spiders, ...

Caffeine has a significant effect on spiders, which is reflected in the construction of their webs. (Photo credit: Wikipedia)

Anais Fournier, 14-Year-Old Girl, Dies After Drinking 2 Energy Drinks.

When covering the story, the reporters are careful to point out that Anais had a mitral valve prolapse.  But what they don’t say is that 10% of the population has some level of mitral valve prolapse and that medical people consider it an incidental finding unless there is significant regurgitation.  It’s a possible risk factor and is monitored.  It has nothing to do with why this poor girl went into cardiac arrest.

What had a great deal more to do with Anais’ death is the fact that her mother didn’t allow her to use caffeine ordinarily.  I’m not in any way faulting the mother.  It is just that her daughter had no tolerance for the drug.

Anais had no idea of the effect of caffeine on her body.  So she didn’t realize that she was a slow metabolizer of caffeine, someone who couldn’t get rid of the stuff quickly enough to get out of the danger zone.  She was the caffeine equivalent of a teetotaler who suddenly decides to go on a night of binge drinking.

I recall the stories of fraternity hazings leading to death.  Those boys were likely not alcoholics.  If they had been, their livers would have converted the alcohol more quickly.

So if Anais had been a five cup-a-day coffee drinker, it is less likely that the two-energy drink dose would have been enough to kill her.  She would have more tolerance, or at least known her limits.

But the larger problem is not that poor Anais did not know her limits.  It’s that far too many of us have stopped thinking of caffeine as a drug.  In the article U.S. TODAY reported that cases of caffeine poisoning have increased over the last few years, from 1,128 in 2005 to 13,114 in 2009.  That’s a twelve-fold increase in four years!  Where are the headlines:  “Caffeine Poisoning Up More Than 1000% In Four Years!”  Instead, caffeine is seen as harmless.  It’s a little like thinking alcohol is harmless.

In some people, some alcohol is not a problem.  In other people, even a little alcohol can cause issues.  With caffeine, even a little can keep a “light weight” up all night.

Caffeine is processed in the liver differently by different people.  So some people will have a genetically higher tolerance.  If you are unfortunate enough to have a genetic polymorphism that slows your processing, then the toxicity of caffeine will be higher for you.

Many people assume that since they are regular caffeine drinkers they are safe.  But even a lower dose of caffeine has effects on the blood pressure.  Individuals who have issues with blood pressure already are more reactive.  Below  is a study showing that people with glaucoma have increased intraocular pressure in response to caffeine.  Hopefully their eye doctor told them to abstain, but he likely did not tell their family to abstain.  If you have a family member with glaucoma, drinking coffee increases your risk.

Tonight on television, my five-year-old saw two ads for five-hour-energy drinks.  He also got an earful about the dangers of caffeine.  It’s time to add caffeine to the list of drugs you need to discuss with your children.

Psychol Assess. 2011 Dec 12. [Epub ahead of print]

Caffeine Expectancy Questionnaire (CaffEQ): Construction, psychometric properties, and associations with caffeine use, caffeine dependence, and other related variables.


Expectancies for drug effects predict drug initiation, use, cessation, and relapse, and may play a causal role in drug effects (i.e., placebo effects). Surprisingly little is known about expectancies for caffeine even though it is the most widely used psychoactive drug in the world. In a series of independent studies, the nature and scope of caffeine expectancies among caffeine consumers and nonconsumers were assessed, and a comprehensive and psychometrically sound Caffeine Expectancy Questionnaire (CaffEQ) was developed. After 2 preliminary studies, the CaffEQ was administered to 1,046 individuals from the general population along with other measures of interest (e.g., caffeine use history, anxiety). Exploratory factor analysis of the CaffEQ yielded a 7-factor solution. Subsequently, an independent sample of 665 individuals completed the CaffEQ and other measures, and a subset (n = 440) completed the CaffEQ again approximately 2 weeks later. Confirmatory factor analysis revealed good model fit, and test-retest reliability was very good. The frequency and quantity of caffeine use were associated with greater expectancies for withdrawal/dependence, energy/work enhancement, appetite suppression, social/mood enhancement, and physical performance enhancement and lower expectancies for anxiety/negative physical effects and sleep disturbance. Caffeine expectancies predicted various caffeine- associated features of substance dependence (e.g., use despite harm, withdrawal incidence and severity, perceived difficulty stopping use, tolerance). Expectancies for caffeine consumed via coffee were stronger than for caffeine consumed via soft drinks or tea. The CaffEQ should facilitate the advancement of our knowledge of caffeine and drug use in general. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

Graefes Arch Clin Exp Ophthalmol. 2011 Mar;249(3):435-42. Epub  2010 Aug 13.

The effect of caffeine on intraocular pressure: a systematic review and meta-analysis.


Department of Ophthalmology and Vision Science, Eye and Ear Nose Throat Hospital, Shanghai Medical School, Fudan University, No.83, Fenyang Road, Shanghai, 200032, People’s Republic of China.



Caffeine is widely consumed, and its effect on intraocular pressure (IOP) has been reported in conflicting data. The aim of this meta-analysis was to quantitatively summarize the effect of caffeine on IOP in normal individuals and in patients with glaucoma or ocular hypertension (OHT).


A comprehensive literature search was performed using the Cochrane Collaboration methodology to identify pertinent randomized controlled trials (RCTs) from the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and EMBASE. A systematic review and meta-analysis was performed. IOP at 0.5 hour (h), 1 h and 1.5 h after caffeine ingestion was the main outcome measurement.


Six RCTs (two parallel-designed and four crossover-designed) evaluating 144 participants fulfilled inclusion criteria. The risk of bias for these studies was uncertain. Among the participants, 103 were normal individuals and 41 were patients with glaucoma or OHT. In normal individuals, the IOPs measured at 0.5 h, 1 h and 1.5 h post-intervention were not affected by ingestion of caffeine. The weighted mean difference (WMD) with 95% confidence intervals (95%CI) for each measurement point were -0.740 (-2.454, 0.974), 0.522 (-0.568, 1.613) and 0.580 (-1.524, 2.684). However, in patients with glaucoma or OHT, IOP increased at each measurement point, with the WMD and 95%CI being 0.347 (0.078, 0.616), 2.395 (1.741,3.049) and 1.998 (1.522,2.474) respectively. No publication bias was detected by either Begg’s or Egger’s test.


Available evidences showed that caffeine had different effects on IOP in different groups of individuals. For normal individuals, IOP was not changed by ingestion of caffeine, while for patients with glaucoma or OHT, IOP increased significantly. More high-quality RCTs are warranted to confirm this. The mechanisms underlying this phenomenon and the clinical significance are to be explored.

Am J Clin Nutr. 2012 Jan;95(1):241-8. Epub  2011 Dec 14.

Genetic determinants of blood pressure responses to caffeine drinking.


Institute of Cardiology, Center of Excellence on Aging, “G. d’Annunzio” University, Chieti, Italy.



The widely observed between-subject variability in cardiovascular responses to coffee may have a genetic basis.


We evaluated acute blood pressure (BP) responses to caffeine and explored whether they are influenced by candidate gene variants affecting caffeine metabolism (for cytochrome P450 1A2), adenosine metabolism (for adenosine receptor and AMP deaminase), or catecholamine receptors.


We recruited 110 healthy male habitual moderate coffee drinkers who refrained from drinking coffee on the day preceding the study. Each subject underwent ambulatory BP monitoring at 6-min intervals for 2 h. Each participant was administered, in a double-blind design, 40 mL of either a decaffeinated coffee preparation plus 3 mg caffeine/kg (caf) or the corresponding vehicle (decaf). The protocol was repeated 24 h later with the alternative preparation. Blood samples were collected for genetic and plasma caffeine and catecholamine evaluations.


Compared with decaf, caf was associated with a mean (± SD) significant increase in systolic BP of 4 ± 12 mm Hg and in diastolic BP of 3 ± 10 mm Hg (P < 0.001 for both). Plasma caffeine and adrenaline increased after caf, but not after decaf. Of 11 gene polymorphisms analyzed, a relation was observed between the ADORA2A TT variant and the change in SBP peak and between the ADRA2B I variant and the changes in both SBP mean and peak; mean peak change in SBP; these variants were associated with increased SBP responses to caf.


Variability in the acute BP response to coffee may be partly explained by genetic polymorphisms of the adenosine A2A receptors and α(2)-adrenergic receptors. This trial is registered at as NCT01330680.





  1. Drinking wto will certanly not kill you.
    I drank 4 redbulls, one after one and only got hyper.

  2. You are blessed with a good liver that rapidly processed the caffeine. Another person in the same situation might face liver failure. Might I suggest taking up a different hobby? Usually the liver slows down as we get older.

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