Caffeine: The Good, The Bad, and The History

Macromoltek, Inc.
5 min readJan 24, 2019

Caffeine has been consumed by humans all over the world for thousands of years. An ancient Chinese legend says the Emperor Shen Nung first discovered tea in 2437 BCE when the wind blew leaves into his boiling water. He was intrigued by the pleasant aroma and invigorated after drinking it [1]. An excavated mausoleum from Xi’an, China for Emperor Jing from the Han Dynasty lends physical evidence to the fact that it was being consumed at least as early as 141 BCE [2]. Coffee, on the other hand, has its own legends from native tribes of the Ethiopian Peninsula. The goat herder Kaldi, who may have lived in the 9th century CE, discovered his goats would not sleep after consuming the berries of a certain plant. He concocted a drink from the berries and stayed alert through long hours of prayer [3]. These coffee berries were eventually transported to Arabia in the 15th century where they are still cultivated today. Even the Americas had their version of a caffeinated drink made from cacao (pronounced ke’kaou). The first civilization to utilize it were the Olmecs of Mexico [4]. The drink was passed on to the Izapa, the Mayans, and finally to Europeans who used the cacao beans to make confections.

Scanning electron micrograph of caffeine crystals. Colorized. Fig 1.

Origin and Purpose

The main sources of caffeine in the U.S. are coffee and tea, but it is also found in cocoa beans, kola nuts, yerba mate, and around 60 other plant species. Many of the plants containing caffeine are found in the temperate zones of different continents around the world. These plant species evolved the use of caffeine independently to address a common problem: pests. Caffeine is a natural pesticide! When a bug ingests the leaves, beans, or stalks of a caffeine-producing plant species, they get a dose of caffeine. Though fairly safe for humans, caffeine is a psychoactive drug that stimulates the autonomic nervous system. In an insect, ingestion results in an increase in the concentration of cyclic adenosine monophosphate (cAMP) — a regulatory agent of protein kinase. Down the metabolic line, this may cause the activation/deactivation of ion channels, promotion of DNA transcription, production of glucose, etc. Basically, the metabolism goes crazy — the circulatory system circulates irregularly with an imbalance of ions while, simultaneously, neurons fire random signals which cause confusion, paralysis, and death. Negative effects are not restricted to insects either. Snails and slugs have been known to suffer cardiac arrest, spiders cannot build effective webs while under the effects, and seedlings cannot germinate in caffeinated soil. Larger animals, such as mammals, are sensitive to caffeine and can easily overdose which will result in dehydration and cardiac arrhythmia possibly leading to death. A person of average height and weight would likely suffer a heart-attack if they managed to consume 10,000 mg of caffeine. This is no mean feat for a human, given that the average cup of coffee only contains 150 mg — but the equivalent dose for a tiny pest is much easier to reach.

Effects on Humans

Caffeine really isn’t all that bad, though. Many studies tout the positive effects of controlled caffeine consumption. The most evident reason is the same reason caffeine is so widely consumed: increased alertness. Remember, caffeine is a psychoactive drug — which means it can pass the blood-brain barrier and affect your brain directly. Our brain cells have two special receptor proteins which are affected by caffeine, known as A1 and A2A. The hormone adenosine binds to both of these receptors, promoting sleepiness and muscle relaxation, and interfering with the release of dopamine — a mood-improving neurotransmitter. Caffeine’s structure is very similar to that of adenosine, and it fits right into both of these receptors’ active sites. When it binds, it blocks adenosine from transmitting its signal, staving off sleepiness, fatigue, and bad moods!

Coffee cherries. Fig 2.

A study done at the Sleep Disorders and Research Center found caffeine increased alertness and auditory vigilance performance in divided attention tests [5]. As a bonus, caffeine has also been shown to improve memory consolidation (i.e. information absorption) but not memory recall [6]. Additionally, both mental effects are shown to be long-lasting, so regular caffeine users maintain the benefits after the caffeine has been metabolized.

Physiologically speaking, all the terrible things caffeine does to insects and bugs are actually a benefit in lower doses. Humans, for example, receive an improved ability to perform endurance tasks due to an increase in metabolism of fat and increased nerve impulse transmission [7]. It also leads to increased glycogen recovery when carbohydrates are consumed with caffeine after exercise [8] — that means less fatigue.

Among the most grandiose of claims about caffeine’s benefits is that it can actually reduce mortality rates! A long-term study viewed mortality rates in patients suffering from Chronic Kidney Disease (CKD) [9]. They found an inverse association between patients that consumed caffeine daily and all-cause mortality. Remember, though, that correlation does not mean causation; most daily caffeine drinkers also had higher education levels, higher incomes, and ingested less saturated fats than participants that did not consume caffeine daily.

Caffeine in the Future

Caffeine has had an important place in human history for centuries. It seems to be ever-present, and always more and more relevant as the pace of our society increases. The benefits have been felt for centuries, so it’s no wonder caffeine remains a huge part of our lives and cultures today.

Links and Citations
1. Jane Reynolds; Phil Gates; Gaden Robinson (1994). 365 Days of Nature and Discovery. New York: Harry N. Adams. p. 44.
2. Houyuan Lu; et al. (7 January 2016). “Earliest tea as evidence for one branch of the Silk Road across the Tibetan Plateau”. Nature. doi:10.1038/srep18955. Retrieved 11 January 2016
3. Weinberg, Bennett Alan; Bealer, Bonnie K. (2001). The world of caffeine. Routledge. pp. 3–4.
4. Coe, Michael D and Sophie. (1996). The True History of Chocolate. Thames & Hudson.

Fig 1. The Wellcome Collection. Credit: Annie Cavanagh and David McCarthy.
Fig 2. Pexels free stock photos. Credit: Daniel Reche.

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Macromoltek, Inc.

Welcome to the Macromoltek blog! We're an Austin-based biotech firm focused on using computers to further the discovery and design of antibodies.