Let’s not grab another coffee!

No matter how productive my meetings “over coffee” were, my body stubbornly rejected my choice, but I wasn’t aware of it! There are always plenty of reasons we choose to blame on, except our very own choices. I didn’t believe it either, so I decided to check it out to see for myself. 

Generally, we want to know as much as possible about a drug molecule long before we even give it to a human being. Drug development is planned this way. Today, we can guesstimate with considerable accuracy the behavior of a molecule inside the body without even synthesizing it in the lab, only by looking at its structure on the paper. Something along the lines of: tell me what it looks like and I will tell you what it can do to you if you swallow it. Such simulations were developed in order to save time and money when new chemical compound structures are considered to be advanced to a future “drug candidate” level. Like any computer simulation, the process has flaws, but way fewer than you would expect! It makes wonders in the sense that it catches failures long before they occur, before money are spent, before any animal or human being gets hurt. Why am I even telling you this? Because this was never done for caffeine before being given to humans, and it shows! We did it all backwards: we enjoyed the coffee first, then we asked what happens. Seriously, we really did that. If you don’t believe it, check out my drug files for our knowledge to-date about caffeine and the coffee history post to see how long after the first sip of coffee did we publish any research related to caffeine.

Last week, knowing how caffeine looks like and knowing what the human body does to it (at least in theory), I decided to ask what will it then do to me when I drink coffee? This sounded incredibly simple at first. Of course, I expected caffeine-induced stimulation and, potentially, increased heart-rate, irritability, insomnia etc. But there was a little evil inside my mind asking “what if it isn’t my coffee causing all the unwanted effects?“. So, I proceeded to investigate. To some extent I already provided you with a few rough calculations in my previous post (click here to see it), but for today’s post I escalated this to a top-notch simulation done by the best pharmacokineticist I worked with – Zack Wintrob.

The hard-core data below shows you how caffeine builds up in someone’s body upon drinking one cup of coffee and how the body will get rid of it. In order to account for some individual differences, the data you see is a simulation assembled for 100 fictitious individuals that would differ in many aspects. Different in what way you may ask? Their body may uptake caffeine slower or faster, their genes may metabolize it quicker or slower, they may take drugs that may influence positively or negatively the way caffeine stays in or leaves their body, etc. The dotted lines marked as “95% CI” (confidence interval) indicate the approximate minimum and maximum amount of circulating caffeine that one could see if we would go ahead to actually test the blood of 100 very different individuals. More precisely, we would expect about 5 of those 100 to have actual levels above or below these limits, but we cannot say how far above or below. However, this simulation does not account for what will happen in the body of an individual with liver or kidney disease, or other health conditions that will dramatically impact the way caffeine is absorbed or eliminated from the body (but it can be done, reach out if you need that info). In brief: you are looking at a snapshot of a pretty good estimate that says “That’s likely the way it happens” when you drink a cup of coffee with that much caffeine in it.

Click the quantity buttons at the left to see the graph corresponding to the actual amount of caffeine you intake each morning. Click on the actual graph-line to learn more about the proportion between caffeine and its metabolite, paraxanthine, and whether or not your circulating caffeine level at that moment in the day exceeds the safety threshold established by the FDA.

You perhaps noticed the green and red dotted thresholds indicating the average caffeine concentration needed to get a stimulation effect and, respectively, the unsafe threshold, the concentration beyond which one is likely to become anxious, irritable, nauseated, and have a faster heart rate and higher blood pressure. The peaks correspond to the one cup of coffee you have at breakfast every day. The concentration gets lower as the day goes by because the body metabolizes caffeine converting it into paraxanthine (and you notice the paraxanthine amount going up). Please note that paraxanthine itself is not an entirely benign metabolite. Itself was shown to stimulate lab animals, but this is another story. For now, just keep in mind that building up paraxanthine is not like drinking water! Now, the entire graph corresponds to one week. You only notice five peaks instead of seven because we assumed that our simulated subjects had no coffee during weekends. While we know that people generally do not give up the coffee during weekends, this exercise will make you think twice about it. Read further to see why!

Let’s play now with the possibility that our 100 fictitious subjects would have had two cups of coffee every day: one for breakfast and another at about lunch time, 4 hours after the first cup of coffee. This means that the body will not get the chance to get rid of the entire amount of caffeine ingested in the morning and will receive another caffeine dose. The two amounts will add-up and will exert a combined effect.

Click the quantity buttons at the left to see the graph corresponding to the actual amount of caffeine you intake with each cup of coffee. Click on the actual graph-line to learn more about the proportion between caffeine and its metabolite, paraxanthine, and whether or not your circulating caffeine level at that moment in the day exceeds the safety threshold established by the FDA. 

I’m sure the much taller peaks caught your attention already. It is quite obvious how the amount in the blood builds up, isn’t it? Check out the difference between the first day (say, Monday) and the fifth day – Friday, in this exercise. If the Friday peak is higher than the previous days peaks, it means that Friday morning did not start from zero, right? Indeed, it didn’t! Even before coffee on Friday, the amount of caffeine in the body was already at the dotted green line’s level. That was perhaps the insomnia on Thursday night! The kind of state of mind when you finally fall asleep at 4 in the morning and you can barely leave the bed when your alarm goes off at 7 am. You are already a zombie and you must have a coffee right away to keep you going. Since you had such a short night sleep, you grab another coffee by 11 am to keep you going. Hmmm… Maybe this is why by the end of Friday you are so done with it and you just can’t take this week any longer! Then you lose your mind in traffic yelling at all the idiots that left work at the same time you did. However, I am willing to bet that, at no point in time, you thought that you may have been overdosed on caffeine this week…

The situation gets even worse. At least mine was because I rarely had two coffees in a day. I normally had three or four with the first holding at least three espresso shots. At times, later on in the day I would have coffee instead of water! So, my caffeine blood level was more like the graph below. Get ready it’s worse than a horror movie… I don’t know why I criticized addicts. I was apparently a caffeine addict myself. Although this graph assumes no caffeine intake in the weekend, I kept having a handful of coffee cups every weekend. I was either working or, best case scenario, going for… a coffee (!!!!) with friends. If I was dining out, the first thing the server offered was a coffee and I didn’t say “no”, NOT EVEN ONCE! I always said “Yes, please!”. If the house coffee wasn’t strong enough and the server recommended their really good quality espresso, I went for that too!

Click the quantity buttons at the left to see the graph corresponding to the actual amount of caffeine you intake with each cup of coffee. Click on the actual graph-line to learn more about the proportion between caffeine and its metabolite, paraxanthine, and whether or not your circulating caffeine level at that moment in the day exceeds the safety threshold established by the FDA. 

What can I say more? Most all of the 100 simulated individuals in the graph above have toxic blood levels of caffeine at the end of each and every single day. Drinking three cups of coffee a day ensures that one can’t follow a sleep-wake cycle. Any normal physiology at this caffeine level will trigger constant jittering throughout the week. Any little bump in the road will make you go bananas and you likely suspect an intestinal virus for the weird gut motility that you experienced throughout the week. Perhaps you already checked many “natural” sleep remedies without any effect and wonder if you will need prescription medication to rest. Also not unheard of is apparently unjustified nausea, restlessness, and hand tremors. Any of these sound familiar? Not sure about you, but they all happened to me.

Same as you, I couldn’t picture my life without coffee. I wanted to enjoy many special flavors, wake up to the wonderful coffee fragrance in the morning and keep “going for a coffee” with my friends, students, and collaborators. That’s when I sat down to plan my coffee intake carefully depending on whether I aimed for the quick stimulation before catching an early morning flight or a few cups throughout the day, each with low caffeine, but without discounting the bitter flavor that I loved so much. My life changed for the better! Click here to check out the coffee recipes that I wrote for my friends and friends of friends that love coffee. If you are curious to learn more about the $1 “negligence” fee, read my post “Mornings are better with coffee” – at the end you are going to find a little story about it. Very much like a laboratory protocol, Dr. Alice’s Coffee Recipes detail step by step how to prepare a very high or very low caffeine-content coffee-cup without discounting its flavor.

That’s it for today! I hope that you learned something new, something that will improve your day-by-day life and health, and – why not? – something that will help you achieve a longer life to enjoy coffee! Should you be curious to read more about caffeine, click here for our knowledge to-date about caffeine. Click like if you enjoyed the post. This will help me write more great quality posts for you in the future. Share what you learned, and stay in good health until next time!

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Perera V, Gross AS, Forrest A, et al. A Pharmacometric Approach to Investigate the Impact of Methylxanthine Abstinence and Caffeine Consumption on CYP1A2 Activity. Drug Metab Distribution 2013;41:1957-1966. 

Beaumont M, Batejat D, Pierard C, et al. Slow release caeine and prolonged (64-h) continuous wakefulness: effects on vigilance and cognitive performance. J Sleep Res 2001;10:265-276.

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Dr. Alice

I teach people how drugs work, when they are needed, and why. My expertise as a pharmacist and researcher allows me to determine whether taking or not taking a drug will pose any risk given all current circumstances that apply at this moment. Many times we don't know unless we try, but other many times walking the extra mile pays off giving in return more wonderful moments and more to give to others.

2 thoughts on “Let’s not grab another coffee!

  1. Thanks for this, Alice! Right now, Noelle’s 16 year old granddaughter is performing an experiment on caffeine’s effect on cell growth for her highschool science fair. Her name is Allison, btw (!) My son told me about your blog post & I’m forwarding the URL to her.

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