Science and Law
4th February 2013

The Science of Caffeine Toxicity

Here are some caffeine basics: Caffeine (scientifically known as 1,3,7-trimethylxanthine, and chemical structure shown below) is the most commonly consumed “psychoactive” substance (enhances alertness, and produces stimulatory effects) in the world.

The Science of Caffeine Toxicity

With all the recent hype related to energy drinks, including Congressional and FDA investigations, we thought it would be interesting to take a step back in this post and focus specifically on the caffeine toxicity concern related to energy drinks.

Here are some caffeine basics: Caffeine (scientifically known as 1,3,7-trimethylxanthine, and chemical structure shown below) is the most commonly consumed “psychoactive” substance (enhances alertness, and produces stimulatory effects) in the world. In the United States, it has been estimated that nearly 90% of adults consume caffeine in forms of coffee, tea, prescription drugs, or other caffeinated food/drink products (including: alertness-promoting medications (e.g. Vivarin), analgesics (e.g. Excedrin), dietary supplements,  prescription medications, energy drinks, and herbal preparations) (Yang 2010).  Its popularity stems from the fact that caffeine falls into the category of compounds known to increase neuronal excitability, which it does by reducing the threshold for excitation.

 

A Caffeine Molecule

Once ingested, caffeine is rapidly absorbed into the bloodstream from the gastrointestinal tract, and maximum blood levels of caffeine are attained within 1.5 hours, although this can occur as quick as 1 hour. As for caffeine’s potential negative effects, these appear to mostly arise from neuronal excitability, and some of the effects can clinically present as nervousness, irritability, insomnia, arrhythmia, tachycardia, and gastrointestinal disturbances.

Based on epidemiological studies assessing the effects of caffeine on cardiovascular health, it was noted that “the data currently available indicate that moderate caffeine intake (four or fewer cups of coffee per day, or ≤ 400mg caffeine / day) does not adversely affect cardiovascular health. There are insufficient epidemiological data to draw any conclusions about the risk for coronary heart disease or mortality associated with consumption of 10 or more cups of coffee per day (≥1000 mg caffeine / day)” (Nawrot 2003).

In Nawrot’s comprehensive review of the literature, the overall conclusion was that “there is ample evidence indicating that for the general population of healthy adults, moderate caffeine intake at a dose level of 400mg / day is not associated with adverse effects such as general toxicity, cardiovascular effects, changes in adult behaviour, increased incidence of cancer and effects on male fertility” (Nawrot 2003).

Further, there have been limited safety studies conducted on energy drinks as a whole, and most adverse effect reports appear to be based mostly on case reports (Campbell 2013). With all drugs, including caffeine, there is individual variability in response to caffeine based on a multitude of factors, including demographic and environmental factors, concomitant drug use, underlying medical conditions, and genetic predisposition. Thus, attributing cause in any specific “caffeine toxicity” case can be daunting.

Interestingly, in a Swedish study, investigators conducted an extensive analysis with a goal of defining toxic doses of caffeine. Of 5,000 autopsies, 1% of subjects had caffeine levels exceeding 10 µg/mL (a cup of coffee is thought to result in blood caffeine levels of 1 to 2 µg/mL).  Over a period of 16 years, 20 cases had caffeine levels greater than 80 µg/mL (a level that has been suggested as potentially lethal).  Although the cause of death for 12 of these patients was documented as caffeine intoxication (mostly due to arrhythmias), several patients were taking other medications in their blood-stream (Sepkowitz, 2013), thus, making an exact cause of death difficult, if not impossible, to pinpoint.

It is not know for sure how much caffeine you would have to ingest to reach a blood level of 80 µg/mL; but it is thought to be in the range of 3 to 10 grams over a relatively short time. Thus, if an energy drink contains a rough estimate of 250 mg of caffeine, one would have to drink at least 12 energy drinks in a few hours to reach this high level. Of course this will vary on a case-to-case basis, especially given all of the factors that can make one more or less susceptible to the effects of caffeine. Alternatively, you can just walk into Starbucks and order a a couple of Green Eyes (Green Eye is a cup of drip coffee with 3 shots of espresso! For a tall size, this equals more than 450 mg of caffeine per drink! Order a Venti Green Eye and watch out!).

Like we have discussed previously, should the issue of caffeine toxicity become adjudicated in the courts, this leads to the interesting issue of specific causation – that is, an evaluation of whether it can be demonstrated that the exposure caused the adverse event or disease state in a specific individual.

Subsribe to our blog to keep up on the latest in energy drinks and caffeine toxicity. Seems like litigation is inevitable, including this suit filed in October 2012 against Monster.

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