Caffeine Topics

The history of caffeine

One may not talk about caffeine history without unveiling its most important part: the history of coffee beans discovery and their travel around the world. So,  grab a cup of coffee if you can and let’s experience an Arabian Night listening to Scheherezade’s tale…

Middle East enjoyed the mysterious power-stimulating bitter beverage for 500 years before sharing it with the rest of the world. It all started around the year 500AD when a young Ethiopian shepherd noticed his sheep behaving unexpectedly after eating the fruits of a certain plant – the soon to amaze the world coffee plant. You see thus that Ethiopia is the country with the oldest and longest history in cultivating coffee. In 525AD when Ethiopians invaded Arabia, they brought the coffee plants to Yemen – another giant coffee producer with an impressively long history in cultivating coffee. In the following 200 years the use of coffee is reported in the Red Sea area and the bitter drink is mentioned by Homer in ~800AD. As the coffee drink is described as medicine in the medical repords of the time (Avicennae Arabum) around 1000AD, Arab traders see the opportunity for its market and bring to their homeland coffee beans for plantation development. The moment is marked as the birth of the Arabic coffee, one of the most tasteful and highly sought after coffee flavors in the world.

In 1200, coffee plant arrives in Turkey were it undergoes for its first heat treatment. It was here that coffee bean were roasted and boiled for the first time. That’s when Turkey established the beginning of its coffee-making history and revolutionized the way we enjoy coffee today. Coffee drinking became a replacement for stimulation and basically substituted the alcohol drinking once alcohol was prohibited by the Koran (1400AD). Less than 100 years later, in 1475, coffee was already introduced to Constantinopole (today’s Istanbul) and the very first coffee shop was open. More interestingly, however, the a new Turkish law was enacted as a consequence of introducing coffee in Turkey. Women gained the right to divorce if the husband failed to provide wife’s daily quota of coffee!

Prior to 1600, no coffee bean escaped Middle East. It was just then that the Italian traders got to introduce coffee to the West, making Venice the receiver of Europe’s first coffee shipment. Thus, you see, that is why the next in the rank of coffee-making culture comes Italy. As anyone may figure, once arrived in Italy, the coffee plant made it straight to the Pope Clement VIII whose advisers urged him to Clement enjoyed it greatly and decided to baptize the cofee instead. Coffee was first sold in pharmacies, as a medicinal remedy.  In less than 50 years, however, Venice opened Europe’s first coffee shop.

In 1607 coffee made it to North America and replaced beer drinking with coffee drinking for breakfast by 1668AD. Interestingly, at the same time, the Grand Vizir in Turkey prohibited coffee drinking and closed all cofee houses. Facing the controversy of the news, the Turkish Ambasador introduces the coffee plant to the court of Louis XIV, in Paris. Coffee continues to experience a wave of protests from England as well were women petitioned against coffee drinking given the fact that their spouses were too involved with attending regular coffee houses meetings with friends. In 1675 King Charles attempted to rule against the coffee houses, but the order was revoked after public protests. The same year marked another big moment in coffee history. In Vienna, the first dash of milk was added to the coffee. They also served it sweetened for the first time.

Paris had its very first coffe shop opened in 1686. “Le Procope” cafe is still in business to these days! Soon after, in 1690, the famous Mocha cofee was smuggled from the Arab port of Mocha. This enabled Dutch to become the first to cultivate coffee in Europe and in their colony of Java. Both coffee varieties are resonant names in today’s coffee culture across the globe. In London, 1700s were the best years ever for coffee lovers:it  seems that the old city had more coffee shops back then than it has today! Shortly after, in 1721, the first coffee-house opens in Berlin and about at the same time, the first coffee plants made it to Guyana. The coffee story get heated at this point with the love affair between Guyana Governor’s wife and the Brazilian Col. de Mello Pahleta. Seduced by the Colonel, she gives him the precious seeds and this is how coffee growing started in Brazil. Although late to the game in a way, Brazil still developed into an impressive coffee producer over the following 300 years! De Mello Pahleta name itself remained famous, although very few know its actual story. Check out the Toronto gem by Trip Advisor for more.

As the coffee seeds made it to Colombia, around 1798, Napoleon himself was reported to have said that he had seven coffee makers permanently on the stove. 1800s bring the fame of the first espresso machine making and, toward the end of the century, on the North American continent the famous “Maxwell House” blend was born, in Nashville, TN. At the same time, coffee seeds arrived in Indo-China and Australia, soon completing their journey around the world when arrived in Kenya and Tanzania.

“Caffeine was first extracted from cocoa beans into its purest form, a white powder, in the 1820s by a German Scientist named Friedrich Ferdinand Runge. Today caffeine is easily extracted and used to make a variety of products that are consumed on a daily basis.”

The twentieth century brought us the instant coffee, the first decaf and the coffee filter. The latter being discovered by a German lady while preparing the “Kaffee Klatsch“, a local tradition of enjoying afternoon coffee and chatting over small matters. It reminds me about Frau Kluthe, one of the kindest ladies I met in Bochum, while going through my training at the Max-Plank Institute in Dortmund, Germany. Bochum was a very small town (same as Dortmund) that I was visiting quite often. Frau Kluthe opened her doors every single day at 3:30pm for Kaffee Klatsch, welcoming neighbors, friends and friends of the friends to have a coffee with her. It was Frau Kluthe that I enjoyed with my first conversation in German! I still remember the first few German words I was able to put together: “Das Wetter is kalt“. Back then I did not realize what an extraordinary memory she was creating for me. I miss you, Frau Kluthe!

When it comes to coffee, the beginning of the twentieth century is heavily marked by the American influence. In 1927, NYC had its first espresso machine – “La Pavloni” – installed at Reggio’s. The legendary machine is still on display there today! A decade later, facing a coffee surplus problem, Nescafe invented the instant coffee by freeze-drying the surplus. It very much seems that this was the first coffee product imported by Switzerland. By 1940, United States imported no less than 70% of the world’s coffee crop! Two decades later, Carnation introduced the coffee mate non-dairy creamer and, at about the same time, the United Nations established for the first time coffee exports quotas.

Seventies were marked by the opening of the first Starbucks coffee shop in Seattle. The store became a chain of 2,000 US coffee shops and over 5,000 outlets worldwide by 1998. Coffee was already the most popular drink in the world with no less than 400 billion coffee cups sold each year! The growth of the coffee business was beyond impressive. U.S. alone had 9,500 coffee shops in 2002 and 25,000 in 2008! The number is estimated to increase to over 50,000 in the near future.

The graph below shows the publication history of caffeine as indexed by PubMed.gov. Caffeine was extracted and published as a cocoa component long before we figured it was in coffee, tea and other sources. Interestingly, you may notice that caffeine gained minimal attention before 1960. It was 70s and beyond that helped us understand why we like coffee and how its actions affect us.

The graph shows the number of articles about caffeine published each year as indexed by PubMed.gov. Click the graph to learn more about the publication history of caffeine.

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How extensive is caffeine consumption?

Roughly a fifth of the studies involving caffeine researched in fact its consumption. As I mentioned above, by 1998 coffee was the most popular beverage. The graph below surely proves the point. Starting with 2000s, caffeine consumption research was a science itself.


The graph shows the number of articles about published about caffeine consumption each year as indexed by PubMed.gov. Click the graph to learn more about the publication history of caffeine consumption.

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How big is caffeine?

Caffeine (C8H10N4O2) has a very small molecule – 194g/mol – similar to adenosine. Its hydrophilicity and lipophilicity enables unique properties that determined its wide spread for nearly 1,500 years. Caffeine is resistant to roasting and boiling, it’s easily extracted in water, and gets absorbed through the gut in less than one hour. It passes through all cellular membranes, and stimulates the central nervous system almost immediately.

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What are the doses and formulations of caffeine?

Most often administered as coffee, or tea, caffeine is today available in many forms: as chocolate, soft drinks (like pepsi, coke, 7-up, etc), caffeine chewing gum, and several over-the-counter medications including headache meds and also weight-loss meds. The doses vary widely, from 10mg to 500mg per serving. Remember that one cup of coffee gives you approximately 100mg of caffeine. A headache medication may very well provide you with at least 50mg of caffeine. Excedrine for instance delivers 65mg of caffeine. If you take it for an afternoon migraine after 2-3 cups of coffee that day, you may find it difficult to fall asleep.
Children are the most likely candidates for chocolate or soft drink induced insomnia. Many parents blame it on the sugar content. It’s the caffeine. First of all, the sucrose content is nearly zero, as they are sweetened with fructose syrup. Then, yeah, fructose may add an extra unneeded energy, but caffeine is indisputable the cause number one of their monkey-jumping at 11 pm! My kids did the same, of course, all until I stopped the caffeine, then the soft drink all together. It took lots of protests and endless pep-talks about the fructose syrup. It worked.

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How does caffeine work?

It blocks adenosine receptors, activates serotonin and noradrenergic mechanisms, and stimulates the release of dopamine. What does this mean? Dopamine works more efficiently when adenosine cannot bind to its receptors. Aside from the feeling of well-being, this triggers enhanced vigilance and improve fatigue. Caffeine increases the energy metabolism of the brain, thus enhancing focus. If adenosine cannot bind to its receptors, the body will make more of it and once having too much, the body will tell the adrenals to make more adrenaline. That is what gets us more alert and energized, but also irritable. The energy consumption process in the brain is now short of oxygen due to the short term blood vessel contraction caused by caffeine. On a longer time frame (a few hours), caffeine stimulates the production of nitric oxide (NO) by the endothelium. NO is a highly beneficial molecule with both antioxidant and antiinflammatory properties.

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Does caffeine cause insomnia?

Well… YES! That is one of its first indications, right? If we drink coffe in the morning to increase alertness, then the same will be the result if we have it in the afternoon. That is something we generally know, however we rarely extrapolate the expectations when consuming other caffeine containing foods, beverages or over the counter medications. Dispensing melatonin to a patient holding a cup of coffee at 10pm makes me think long-distance travel or night-shift working. I then have to stop and ask: “Is this medication for yourself?“. Nine out of 10 cases the answer is yes. Then I have to ask: “I figure you must be working tonight?”. This is when the rational patient tells me “Yeah, that’s why I need the melatonin tomorrow morning and I was out of it” (or something along these lines). But once in a blue moon I also hear “No, I am not. Why?“. That’s when I know I’ll make a difference in someone’s life. The discussion is even more interesting when the patient checks out caffeine containing migraine medication and melatonin. Or even better, picks up a prescription for a sleeping pill and also checks out over-the-counter caffeine containing migraine meds (that are not on-sale!) and a 2L bottle of regular coke. As a pharmacist, I have a brain-freeze moment. Does your doctor know what you’re doing??

How often do I see any of the situations above? More often than you want to hear!


The graph shows the number of articles about published about caffeine and insomnia each year as indexed by PubMed.gov. Click the graph to learn more about the publication history of caffeine and insomnia.

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Is caffeine action dependent on body weight?

Absolutely! In fact, the this relationship was studied closely not that much to ensure any risk for toxicity, but in fact to induce weight loss. Given the dose-dependent increase of the energy metabolism, high doses of caffeine are used in several weight loss over-the-counter medications. Their safety is highly debated and many argue that they should not be sold without a prescription for this very reason. If 4-5 cups of coffee in a day (~5-700mg caffeine) may be concerning for safety (increased heart rate, irregular heart beat dizziness, anxiety or restlessness, nervousness, nausea etc), you might get an idea about what doses over 1-2 grams of caffeine may do!

Based on my own experience trying such (stupid?) weight loss strategy, I can tell you that the feeling of absorbing a tone of caffeine all at once isn’t pleasant. To be more precise: it was one of the few times in my life when I thought I may die. Did I lose weight: yes, I did – about 5 pounds after one single pill. That was because my resting metabolic rate increased by 10-20% for at least 3 days! Would I try this again? Absolutely never and I DO NOT recommend it to anyone! I was lucky to make it. However, people do study it intensely. The graph below should give you an idea about how the interest related to weight loss impacted caffeine research.


The graph shows the number of articles about published about caffeine and weight each year as indexed by PubMed.gov. Click the graph to learn more about the publication history of caffeine and weight.

How does caffeine intake impact obesity?

Caffeine is thought to lower the overall body weight by increasing the resting metabolic rate. See above the details I provided for the role of caffeine in weight loss.
Interestingly, however, lower (read regular) doses of caffeine may be entirely ineffective in individuals with body mass indexes (BMIs) over 30 (overweight, obese and morbidly obese). That is due to the exceptional penetrability of the caffeine molecules. The bigger the BMI, the bigger the drug distribution, hence the lower the effect from an otherwise regular cup of coffee. Thus, individuals with bigger body weight can “tolerate” bigger amounts of caffeine. In fact, it would be more correct to say that they do not get an effect from amounts that might be sufficient for individuals with lower BMIs. So, based on this information, one may assume that the considerably higher caffeine doses used for weight loss are justified. They could be, but never attempt such without the direct supervision of a clinical professional licensed to give you the first aid if needed.


The graph shows the number of articles about published about caffeine and obesity each year as indexed by PubMed.gov. Click the graph to learn more about the publication history of caffeine and obesity.

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Is caffeine OK for individuals with diabetes mellitus?

The safe answer here is “It depends“. There are always exceptions, but, as a rule of thumb, if the individual requires injectable insulin for the management of diabetes, then caffeine may not be safe. If the renal function is impaired as a result of advanced diabetes, it is may not be safe to take caffeine. If aside from diabetes the patient was diagnosed with liver disease, a seizure condition, or essential hypertension, I will surely recommend against it.

However, caffeine is studied in relationship with diabetes. Its benefit against migraines and as adjuvant in weight loss did open path for many studies involving patients diagnosed with diabetes.  Reach out directly if you have a question or require clarification!


The graph shows the number of articles about published about caffeine and diabetes each year as indexed by PubMed.gov. Click the graph to learn more about the publication history of caffeine and diabetes.

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Does caffeine impact cancer risk?

The short answer – it very well may! How exactly and at what doses it is still premature to say. There may also be a significant bias in these determinations since individuals drinking (tolerating) coffee may be in fact healthier than those who do not. Nevertheless, given the interaction potential of caffeine with a handful of other drugs, sicker patients taking more medications and being at a higher risk for cancer may simply be recommended not to drink coffee. We do not know for sure, but the jury is out to find out more. For now, clearly the graph below demonstrates that there is an intensive research activity evaluating caffeine and cancer.

The graph shows the number of articles about published about caffeine and cancer each year as indexed by PubMed.gov. Click the graph to learn more about the publication history of caffeine and cancer.

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Does caffeine impact blood pressure?

The short answer – YES, it does, because of the adrenaline produced in response to the caffeine dose! But do not mistaken heart rate and blood pressure for the same concept. Heart rate represents the number of heart beats in a minute. The blood pressure represents the amount of pressure in the arteries during the contraction of the heart muscle (systolic) and the pressure between heart beats (diastolic). Caffeine does increase heart rate. However, it increases blood pressure only until sufficient nitric oxide is produced, at what point it becomes, in fact, a vasodilator. So, caffeine may cause a spike in blood pressure (10-13 mm Hg), then a profound vasodilation. Individuals receiving antihypertensive medications for high blood pressure may, in fact, be impacted more severly by the hypotensive episode followed by dizziness and vertigo. There is also more to this story. First, it varies from a person to another how long it takes between the blood pressure spike and the vasodilation. Many individuals chose to take additional blood pressure medication during or soon after the spike and this exacerbates terribly the vasodilation afterwards.

Long story short: if you really-really like coffee and were diagnosed with hypertension, you may want to have a clinician coaching you through identifying the safe coffee cup for you. Take a look at my coffee recipes and find out how I lower the caffeine content in my coffee. Learn to drink such low caffeine coffee slowly, over long periods of time and watch carefully any changes in your liver and kidney function (and blood pressure, of course!). The graph I provide for you shows all the published studies evaluating caffeine and blood pressure. Quite a bit of research, take a look!

The graph shows the number of articles about published about caffeine and blood pressure each year as indexed by PubMed.gov. Click the graph to learn more about the publication history of caffeine and blood pressure.

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What should I do if I have side effects?

Caffeine is reported as generally “safe”, side effects being noted with high doses or with normal doses administered too quickly. I will not count here insomnia, since that is rarely an unwanted side effect. If insomnia is uninteded, DO NOT take sleeping pills of any kind. They won’t work. Best possible option is to drink plenty of water (absolutely no alcohol) and wait for the time to pass. Unless isn’t crystal clear: don’t do it again.

Most individuals get concerned about the caffeine effect when they experience increased heart and respiration rate (tachycardia and tachypnea), palpitations, and/or blood pressure. Did this happen because you had an extra cup of coffee as compared to usual or because you took a 2 grams caffeine dose for weight loss? If anything above a total of 500mg caffeine in total, call an ambulance immediately. Do the same if you have a special health condition that you are aware of. If is less life-threatening, check your pulse and blood pressure and count your respiration per minute. Write them down and reach out to a clinician you trust to assess how significant the situation is. Drink plenty of water and, if you have, take a laxative until some one with clinical experience can assess the situation.

Although often seen with caffeine overdoses, irritability, nervousness, restlessness, and anxiety are rarely noticed or reported by the user – potentially being attributed to other reasons than caffeine intake. Stomach irritation goes hand in hand with nausea and vomiting and are often reported in individuals that have a history of gastroesophageal reflux disease, peptic ulcer disease or gastritis.

I provide here for you a very good first aid resource link. Read it ahead of time, being aware is better than being unprepared!

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© Copyrighted – All rights reserved to Dr. Alice C. Ceacareanu

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