Genuine question: does that mean when people die after consuming way too much caffeine, it's not because of "caffeine toxicity" per se, but because the effects of the caffeine put too much strain on their body?

Caffeine doesn't only come in coffee. Caffeine pills and powders make overdoses much easier. For example: https://pmc.ncbi.nlm.nih.gov/articles/PMC8824417/

Nobody is dying from the caffeine in coffee (like 50-100mg per cup). According to the NIH, LD50 of caffeine is 150-200mg/kg (so say 10g for a small person). That's like 100 cups of coffee. Even with espresso that's hard to imagine.

It would need to be in powder form or concentrated in something far beyond natural levels of coffee/tea/matcha/etc.

1 cup filter coffee can be 170mg or more. And LD50 isn’t really relevant here, even LD1 levels are deadly to hundreds of millions of people. It’s entirely possible for what some might consider a “normal” amount of coffee to be deadly to many. See other comment for espresso calculations.

https://m.youtube.com/watch?v=etnMr8oUSDo

LD50 is (an estimate) of the 50th percentile (i.e., 50% chance of dying), but that doesn't mean it's linear. It _certainly_ doesn't mean that 1% of people will die at 2% of that value, which I think is what you're implying.

The lowest example of a lethal dose I can find in the literature is 57mg/kg. Caffeine overdoses are so rare that we don't know the true distribution, but it's clearly not the case that millions people will die from a few coffees.

Your other comment calculated the lethal dose as *a gallon of espresso*. That's like 125 shots. That is not a remotely normal amount of coffee. It would take multiple people over an hour to make that much espresso for you.

That’s not what I was implying at all I have no clue how you arrived at that. I’m saying an LD1 does exist – it’s the dose that would be fatal to 1% of a population (and further a LD0.1 and 0.0001 exist). These doses are lower than the LD50, fatal to millions, and approach what some would consider normal. For instance: https://www.nbcnews.com/news/amp/ncna759716

The cooldown period built into HN is there for a reason: taking time to reflect on messages and do any necessary background research makes for better discussions than impulsively saying whatever is top of mind. I suggest you use this time to understand what an LD50 actually is and how the concept generalizes.

(cc @dang, seeing this growing trend of people misunderstanding the missing reply button and evading the timer via edits, perhaps UI affordances could be developed to better introduce folks to the feature?)

LD1 would be deadly to about 80 million people

Right, there’s not zero population risk. But for assessing the risk to any randomly sampled person, the risk approaches zero.

Classic bayesian error. The population in question here isn’t the globe, but rather people who have already died from caffeine related causes. Naturally the rate of increased caffeine sensitivity amongst those folks will be different from the population at large.

I never said randomly selection from the global population. The point still holds, even if sampling from only those who have died from caffeine: the LD1 dose, by definition, is still safe for almost all the population. That’s why arguing about LD1 or LD.0001 isn’t particularly useful and comes across as overly pedantic.

Also, FWIW the LD50 can be calculated with censored populations (ie not all subjects have died.) Think about it: if I administer a dose that kills half but leaves the other half living, the LD50 remains unchanged even if I continue increasing the dosage until all have died (or not). LD50 does not require a complete set.

Ok, I think we’re on the same page.

"It's entirely possible" isn't the way to think about estimating risk because it assumes the risk goal is zero (ie any risk > 0 means the outcome is "possible"). A dose greater than LD50 means "more probable than not" of dying, absent additional information, which is a more appropriate framing.

Similarly with caffeine content "can be". All kinds of variables like roasting time affect the dose But the semi-standardized dose for a cup of coffee is about 100mg. Related to your link, they are a much larger cup of coffee for comparison. If you normalize it to the standard coffee size, it comes to 100mg caffeine, so right in line with what would be expected.

LD50 for espresso is roughly 1 gallon per 50kg body mass. I wouldn’t want to, but I could drink 2 gallons of water without significant issue. If we accept that some people will naturally have a lower tolerance (and that espresso isn’t the strongest drink in the world), it’s not hard to see a caffeine overdose itself being fatal.

(based on 36ml espresso having 110mg caffeine, LD50 caffeine is 150-200mg/kg)

I see one problem here: caffeine is soluble in water and a diuretic, meaning anyone attempting suicide by coffee would have a bad time doing it.

Healthy kidneys work through around a litre of blood a minute, so my guess is that, ahem, "breaking the seal" would keep caffeine levels in check.

1 gallon = 7.6 l, and anectada from Wikipedia (referenced to https://www.scientificamerican.com/article/strange-but-true-...) says 6 l in 3 hours killed a man. Half-life of caffeine is approximately 5 h, so quite similar.

1 gal is about half that (3.8 liters)

UK/imperial gallon is 4.5l US gallon is 3.78l more people used to use imperial than US but now most commonwealth economies are metric.

Fair enough, but it seems per clear that the OP was referring to US gal but the math was just off by double.

Let’s go back to the OP, which asked about coffee. A quick search shows the LD50 for coffee is about 118 cups. At 6 oz per cup, that’s roughly 21 liters. The LD50 for water is listed as 6 liters (below what you’d drink “without significant issue” btw). So someone is much more likely reach the LD50 for water well before caffeine when drinking coffee.

Are there other caffeine delivery mechanisms that differ? Of course, but that’s not what the OP asked. The question was about the toxicity of coffee. That’s why it’s not worth arguing when something like caffeine powder provides the majority of ODs. Likewise there’s going to be variation in toxicity between individuals but those numbers are intended to be generalizable numbers to a population.