Last month, news of the tragic death of a British personal trainer in January of 2021 made the rounds. 29-year-old Tom Mansfield, a father of two young children who also worked as a security guard, miscalculated the amount of legally purchased pure caffeine powder that he would add to a beverage by a significant, and ultimately deadly, amount. Soon after drinking the concoction, he began clutching his chest and complaining of an unusually rapid heart rate. Within minutes of developing symptoms, he went into cardiac arrest and was not able to be saved despite what sounds like a valiant effort by medical professionals on the scene.

Mansfield had purchased a 100-gram container of pure caffeine powder and likely planned to add between 60 and 300 milligrams to his drink, though the amount appears to be an assumption based on typical pre-workout doses. According to several news reports, no scoop was provided by the company, Blackburn Distributions, to aid in measuring a safe amount of the powder. This was a fact focused heavily on by Coroner John Gittins during an inquest last month:

Mr Gittins added that he has since been “massively reassured” that action has been taken to help prevent similar cases from occurring in the future with this brand of caffeine powder due to the provision of a scoop and an A4 instruction sheet in all new packets. Had these scoops been provided at the time, Mr Mansfield would likely still be alive today, the coroner said in his conclusion.

Coroner Gittins probably shouldn’t feel that confident in that assertion, but the provision of a measuring scoop and additional warnings along with these products might reduce the chance of accidental fatal overdose. There is, of course, a much better option. I’ll get into the nuance of this shortly. But first, a brief primer on caffeine and caffeine toxicity.

The most popular psychoactive drug in the world

Though I have never been a fan of coffee or tea, like roughly 90% of the world’s adult population I do consume caffeine daily, mostly in the form of chocolate and Diet Coke. When I wrote about the dangers of energy drinks in the pediatric population back in 2014, I discussed my strategic use of caffeine pills, which typically contain 200 milligrams of caffeine, when I needed a boost in alertness or athletic vigor. I generally avoided caffeine on other days in order to stave off the development of tolerance.

Over the next several years I found myself taking a caffeine pill almost daily, largely because I became more dedicated to running and was logging 5-6 miles most days. I also began having more frequent headaches. After finally making the connection between my headaches and caffeine withdrawal in early 2020, I stopped taking the pills prior to workouts and now only get caffeine in my diet as described above. I sometimes miss the boost in endurance I enjoyed while taking a caffeine pill prior to going for a run, but I now very rarely have a migraine, which is a trade off that I’m very happy to make.

Mr. Mansfield, the unfortunate British personal trainer, also used caffeine for a boost in athletic performance. As I mentioned above, his goal was likely to make a drink with about the same amount of caffeine as in my caffeine pills. To do this using pure caffeine powder, at least according to the reports, he used a digital scale. And though it is not outright stated that this was the first time he had worked with pure caffeine powder, or this particular digital scale, it certainly sounds like this was the case.

First off, he used a standard kitchen scale with a minimum weight capacity of 2 grams, meaning the endeavor was doomed from the start because his goal was around 3% to 15% of 2 grams. Kitchen scales with that minimum weight capacity typically round to the nearest gram. Some small pocket scales measure in increments of .1 grams (100 milligrams), but that’s not the kind of scale he owned. So a combination of using an inappropriate scale, if he actually used it, and seriously botching the conversion from grams to milligrams could have easily resulted in Mansfield putting much more caffeine powder into his drink than he realized.

The news articles, which were primarily based on information from the government inquest, claimed that he was shooting for 60-300 milligrams, but again that’s just an assumption. Many online resources of questionable legitimacy recommend amounts up to 500 milligrams as a pre-workout supplement. Ultimately, nobody witnessed him preparing the drink so we will never know what really happened. There is not a small chance that he just dumped some of the powder in his drink without any thought at all.

This is your brain on caffeine

Most people who consume caffeine every day, which again is close to all adults and even most older kids, take in at least a couple hundred milligrams in the form of coffee, tea, energy drinks, food, or supplements. Most experts would agree that intake of 2.5 milligrams per kilogram of body weight over a day is unlikely to cause any concerning symptoms in older kids and adults, although some people are more sensitive than others or have underlying conditions that put them at risk of adverse effects. There is more nuance to this issue, particularly when it comes to withdrawal symptoms like my headaches, or sleep deprivation in adolescents, but I’m going to focus on severe toxicity in this post.

Regardless of the source, caffeine is fairly quickly absorbed in the gastrointestinal tract (< 1 hour) and acts as a potent antagonist of adenosine receptors in both the peripheral and central nervous system. Caffeine is a non-selective adenosine receptor antagonist, and there are different receptors in different parts of the body that lead to different physiologic effects when stimulated, so caffeine alters physiology in a variety of interesting ways, some of which are clinically meaningful. The one we tend to care about most though is its role as a central nervous system stimulant.

The longer we go without sleep, the more adenosine builds up in our neuronal synapses and the more a specific type of adenosine receptor in the ventrolateral preoptic area of the brain is stimulated, which results in us feeling sleepy. If these receptors are plugged up with caffeine molecules, preventing adenosine from binding to them, you feel more alert until eventually the sheer amount of adenosine overwhelms the blockade or the caffeine in the adenosine receptor is degraded, which usually takes 2-4 hours depending on individual genetics.

There is not compelling evidence to support claims that caffeine use leads to dependence or abuse, but tolerance does develop and many people, though not everyone, will experience withdrawal symptoms upon abstinence if they have been consuming at least 100 milligrams every day for at least a few consecutive days. Headache is the most common symptom, but withdrawal can also involve fatigue, decreased alertness, drowsiness, depressed mood, and irritability. Withdrawal can occur within 12-24 hours of consuming caffeine, last more than a week, and in people who are consuming large daily doses of caffeine it might feel like the flu, complete with nausea and muscle aches.

Caffeine toxicity and the role of weak regulations

When someone consumes large amounts of caffeine, the definition of which varies a bit based on things like size, tolerance, and genetics, they can experience a number of potential adverse effects ranging from annoying to deadly. As experienced by Mr. Mansfield, heart palpitations from an abnormally rapid pulse, tremors, and agitation are common complaints, as is an upset stomach. More severe toxicity can present with dangerous alterations in the hearts rhythm, which can result in cardiac arrest, hallucinations, and seizures. Death, though uncommon, can occur.

According to the FDA, more serious toxic effects, such as seizures, are more likely to be seen once someone has consumed around 1.2 grams in a short period of time. According to a 2018 review of caffeine toxicology in Toxicology Reports, cases of fatal overdoses tend to involve much larger amounts:

In cases of overdose, often intentional but sometimes undetermined and unintentional, at least 5 g or more (i.e., often around 10 g but up to 50 g) have been ingested leading to fatalities particularly if the individuals are not treated in time or at all. However, doses up to 50 g have also been treated successfully otherwise. Some have indicated that after a dose of around 1 g, toxic symptoms begin to manifest, a dose of 2 g requires hospitalization, while higher doses (e.g., typically 5 g or more) could be lethal. However, some have determined that as little as 3 g could be lethal under certain circumstances.

We don’t know if Mansfield had any underlying health problems that put him at higher risk of cardiac arrest from a caffeine overdose, or if he was taking additional medications or supplements that raised the chance of an adverse reaction. We don’t know if his metabolism of caffeine was impacted by genetic factors that increased (or decreased) the effect of caffeine on his physiology. Regardless, it was estimated that he ingested so much caffeine in a matter of only a few minutes that none of that really mattered.

This conclusion is based on the finding of a caffeine level of 392 milligrams per liter of blood during a post-mortem analysis. A regular 8-ounce cup of filtered coffee drunk in a short period of time would raise a typical adult’s blood level of caffeine by about 2 to 4 milligrams per liter. This means that Mansfield consumed the equivalent of anywhere from 98 to 196 cups of coffee in one go. 8 ounces of regular coffee contains anywhere from 70 to 140 milligrams of caffeine. Using the lower figure, he ingested a minimum of almost 7 grams of caffeine, which could easily have killed him. But, using the upper limit of cups and caffeine per cup, Mansfield potentially drank nearly 27.5 grams of caffeine.

One thing made clear in the many articles on this tragic case, and in my review of British food and drug regulations, is that there are no laws that prevent the sale of pure caffeine, either powder or liquid, in bulk quantities. There are no laws that stipulate what kind of measuring aids or even what if any warnings must be included along with these products. As I mentioned earlier, the manufacturer has announced that it now voluntarily provides a measuring scoop and more detailed information on both how to measure a safe dose and the risk of overdose. This isn’t enough.

There are no standard measuring scoops or spoons that are going to be found in most kitchens that could accurately measure amounts as small as 60 or even 300 milligrams accurately. So the claim that providing a small scoop with pure caffeine powder sales sounds like a reasonable safety measure. To give you an idea of how tiny these scoops are, below is a 100 milligram scoop placed next to a dime for scale.

If accompanied by clear warning labels, use of a scoop such as this might significantly reduce the risk of extreme overdose. Mansfield likely would have realized something was off if he found himself putting tens or even hundreds of scoops on to his kitchen scale, which would be necessary to reach 7 to almost 28 grams of powder. But there could be a bit of a false sense of security when it comes to less severe overdoses depending on if a consumer uses a heaping scoop or packs the powder into each scoop, which could inadvertently add hundreds of extra milligrams of caffeine depending on the desired amount. And a scoop wouldn’t protect against conversion errors when using a scale that can’t accommodate such small amounts.

Better measures are needed to prevent inaccurate measurements

The solution to this issue is to prevent the sale of pure caffeine powder or liquid. It’s far too risky, even with scoops and warnings, to rely on measuring out such small amounts at home. This problem could easily be solved by selling reasonable servings of caffeine powder or liquid in individual containers for adding to drinks, or by producing caffeine tablets, like my old migraine-inducing nemesis, that dissolve in liquid. But honestly is there really a need to ever add caffeine to a homemade drink?

This post serves as a bit of an update to a 2015 post by Scott Gavura, where he discusses two fatal cases of caffeine overdose and rightfully blames weak regulations in the United States. At the time, the FDA had recognized the danger of pure caffeine powder being sold in bulk for consumer use but had only issued toothless warnings. Scott predicted that more deaths would occur:

No recalls, or “stop sales” orders. Just a warning to consumers…As long as we maintain a regulatory double-standard for supplements and “natural” products, there is not likely to be much change, and we can probably expect more people to die from caffeine powder overdoses.

I have some good news to report as I finish up this post. Since 2015, the FDA has done more than simply warn the public about the risk of caffeine overdose. For example, in 2018 they publicly went after companies selling pure caffeine products, giving them 15 days to stop or face consequences such as seizure and/or injunction. This change in approach is based on the decision to consider these products to be adulterated under section 402(f)(1)(A) of the Federal Food, Drug, and Cosmetic Act:

(f)Dietary supplement or ingredient: safety

(1) If it is a dietary supplement or contains a dietary ingredient that –

(A) presents a significant or unreasonable risk of illness or injury under-

(i)conditions of use recommended or suggested in labeling, or

(ii)if no conditions of use are suggested or recommended in the labeling, under ordinary conditions of use;

Manufacturers of pure caffeine powder in the United States now will not sell to individual consumers and their websites contain warnings such as this:

Warning: Owing to the risk of personal HARM, INJURY, or DEATH with the use or misuse of Pure Caffeine Powder sales are limited to qualified commercial, scientific and business buyers only. Sales to the general public are not allowed. To be considered for approval submit the form below with documents, or if previously approved log into your account to purchase.

This doesn’t mean that the risk of overdose in the United States has been completely removed. I wouldn’t trust the guy behind the counter making me a caffeinated smoothie with this stuff any more than I would trust myself, though a business would at least be more likely to use appropriate scales and scoops. And we all know how it tends to go in the supplement industry. There will likely always be unscrupulous companies willing to take a chance for profit, and there are still plenty of products that, while not as risky as a homemade drink made with added pure caffeine powder, contain absurd amounts of the drug and can result in overdose. But we have at least moved in the right direction.

Author

  • Clay Jones, M.D. is a pediatrician and a regular contributor to the Science-Based Medicine blog. He primarily cares for healthy newborns and hospitalized children, and devotes his full time to educating pediatric residents and medical students. Dr. Jones first became aware of and interested in the incursion of pseudoscience into his chosen profession while completing his pediatric residency at Vanderbilt Children’s Hospital a decade ago. He has since focused his efforts on teaching the application of critical thinking and scientific skepticism to the practice of pediatric medicine. Dr. Jones has no conflicts of interest to disclose and no ties to the pharmaceutical industry. He can be found on Twitter as @SBMPediatrics and is the co-host of The Prism Podcast with fellow SBM contributor Grant Ritchey. The comments expressed by Dr. Jones are his own and do not represent the views or opinions of Newton-Wellesley Hospital or its administration.

Posted by Clay Jones

Clay Jones, M.D. is a pediatrician and a regular contributor to the Science-Based Medicine blog. He primarily cares for healthy newborns and hospitalized children, and devotes his full time to educating pediatric residents and medical students. Dr. Jones first became aware of and interested in the incursion of pseudoscience into his chosen profession while completing his pediatric residency at Vanderbilt Children’s Hospital a decade ago. He has since focused his efforts on teaching the application of critical thinking and scientific skepticism to the practice of pediatric medicine. Dr. Jones has no conflicts of interest to disclose and no ties to the pharmaceutical industry. He can be found on Twitter as @SBMPediatrics and is the co-host of The Prism Podcast with fellow SBM contributor Grant Ritchey. The comments expressed by Dr. Jones are his own and do not represent the views or opinions of Newton-Wellesley Hospital or its administration.