By Eugene Y. Chan, M.D.
Recent news about tragic death of Anais Fournier hit the web. She was 14 and she died after consuming two 24-ounce Monster Energy drinks over a 24-hour period. She had an underlying heart arrhythmia that may have predisposed her to the adverse effects of caffeine.
Caffeine is a small molecule alkaloid that is found in many different types of plants. It has a receptor-based mechanism of action that antagonizes the action of adenosine. In clinical medicine, adenosine is sometimes utilized to treat certain irregular heartbeats, including some supraventricular tachycardias. Decreasing the action of adenosine can therefore lead to a faster heart rate and can also predispose the heart to irregular heartbeats. In the case of the very unfortunate 14-year old, she consumed caffeine which decreased action of the adenosine, thus increasing her likelihood of a fatal arrhythmia.
How much is too much? One may say, “Let us calculate the lethal dose.” The LD50, or lethal dose for killing 50% of tested animals, for rats is 192 mg/kg. Extrapolating this to a 14-year old weighing 50 kg, this LD50 is 9.6 grams of caffeine. Of course, these studies were not conducted in humans so this is only a ballpark estimate. In a typical energy drink, there is approximately 200 – 300 mg of caffeine, although in some energy drinks, the actual amount is unclear, based on how the products are labeled. We can assume that Anais probably consumed < 1 gram of caffeine from her two energy drinks, yet this was a fatal dose for her. What the LD50 calculation is missing is both an understanding of both statistics as well as pharmacogenomics. Statistics tells us that some individuals may very well have adverse events at a much lower dose of caffeine. Part of this is based on a genetic makeup and how we react to certain molecules. This is called pharmacogenomics. In the case of Anais, she likely had a genetic cause of her underlying cardiac arrhythmia. She may very well have been a slow metabolizer of caffeine, also based on her genetic makeup, leading this molecule to linger in her system much longer than that of her counterparts. Without a whole genome study, of course, we would never know.
Overall, the lesson here is that receptor-based molecules, such as caffeine, can be extremely dangerous, depending on the specifics of your medical and genetic background. For most people it may be fine, for others, it can unfortunately take push you over the threshold of safety.