Would You Like Your Coffee With or Without 1,3,7-Trimethylxanthine?

Phoebe Ahn

In many countries around the world such as the US, France, Finland, South Korea and many more, a cup of coffee has become a staple way for people to start their morning. This beloved beverage actually has its roots in Ethiopia. According to one legend, a goat-herder was roaming the countryside of the Ethiopian kingdom of Kaffa when he noticed his goats eating fruit from a strange plant. The goats became so energetic and erratic that the goat-herder was unable to sleep. Some versions say the goat-herder threw the “magic berries” into the fire and the smell attracted some monks who decided to make it into a drink while others recount the goat-herder himself inventing coffee and reporting it to the monastery. Yet, one thing remains consistent in both versions: the caffeinated effects on the goats. For this reason, coffee, or perhaps more accurately, caffeine is one of the most consumed chemicals all around the world. According to a caffeine consumption count starting from 2012, an average of roughly 157.98 million 60-kilogram bags of coffee are consumed every year worldwide. In Finland, coffee is often poured over chunks of cheese curds. In Malaysia, coffee is often mixed with black tea and milk. British people often dunk digestives into coffee to soften the cookie. Caffeine has reached the hearts (and perhaps brains) of many, yet as ubiquitous as caffeine is in our daily lives, research into caffeine as a chemical has barely begun to scratch the surface. Recently, a 2021 study analyzed potential pharmaceutical uses of caffeine as a pain reliever and prevention for neurodegenerative diseases including dementia, Alzheimer’s, and Parkinson’s.

Caffeine is a psychostimulant that occurs naturally in coffee beans, tea leaves, cocoa beans, kola nuts, and can also be added to many foods and beverages. Chemically, caffeine is also known as 1,3,7-Trimethylxanthine. It acts mainly as an adenosine receptor antagonist, meaning that it competes with the receptor for adenosine—a chemical found in human cells—and blocks its effects. Our central nervous system is made up of millions of neurons, cells that send signals to regulate our body. A neuron simplified is made up of three main parts, the organelle-carrying cell body, the dendrites that receive signals, and the tail that sends signals. The branching ends of the tail sending signals to the dendrites are known as synaptic terminals and the minuscule gap between the terminal endings and the dendrites is called the synapse. So how exactly does this lead to the energy kick we feel when we sip some coffee? When the chemical adenosine, naturally produced by our body, binds to the receptors located on the neuron’s dendrites, neural activity slows down. This neurotransmitter is associated with sleep, blood vessel dilation, and oxygenation. However, when caffeine blocks the receptor site, the adenosine molecules are unable to trigger the body’s relaxation state. Meanwhile, caffeine speeds up neural activity which, at the moment, lacks a proper braking mechanism. The increased activation of the nervous system sends more signals to a certain part of the brain called the pituitary gland to secrete more hormones which in turn signal the adrenal glands to produce more adrenaline. This is essentially what the adrenaline rush one feels when that first cup of coffee hits you as this “fight-or-flight” hormone produces a sudden burst of energy. To put it simply, caffeine blocks our braking system while simultaneously sending signals to our brain to produce more adrenaline resulting in a caffeine rush.

In recent years, there has been a movement to utilize some of caffeine’s unique properties in medicine. The World Health Organization (WHO) has already listed caffeine as an effective brain penetrant that has many relevant health related side-effects. Alone, the chemical may not have significant effects, but when combined with other drugs or pre-existing conditions, many studies have found incredible discoveries. In the 2021 study mentioned, one of the properties mentioned was caffeine’s potential as an analgesic adjuvant. Analgesic adjuvants do not necessarily reduce pain on their own, but rather enhance the effect of other analgesic agents. Current evidence suggests that this heightened effect is due to caffeine’s adenosine antagonist abilities. When the receptor for adenosine, also known as A2A receptor, is blockaded by normal analgesic drugs, pain relief is induced.

One particularly attractive prospective topic mentioned in the 2021 research is caffeine’s protective effect against neurodegenerative diseases such as dementia, Alzheimer’s disease, and Parkinson’s disease. According to Dr. Joanna Fiddler, a professor at Cornell University researching nutritional sciences and currently teaching a course on nutrition, health and society, “[w]ith review of scientific evidence, three to five 8-oz cups*day-1, ~400 mg*day-1 of caffeine, may lower risk of type 2 diabetes, certain cancers, CVD [cardiovascular disease], and Parkinson’s disease.” Experiment done on mice administered 1.5 mg of caffeine per day in drinking water found an improved memory performance and lower amyloid-beta protein levels in later life. Amyloid proteins when aggregated can form deposits in blood vessels, lowering the blood vessels’ flexibility thus making them move prone to breakage. Another 10 year-long study following 676 male participants revealed lower cognitive decline in men who drank three cups of coffee per day. A similar study was done following patients for 21 years for dementia. The lowest risk appeared to be correlated with three to five cups of coffee per day. One explanation for this chemical’s protective effects point to the A2A blockade as the key factor. When A2A receptors in the hippocampus are blocked, it appears to prevent the build up of amyloid-beta proteins in the brain. Additionally, some studies have shown men who have been administered caffeine have increased blood oxygen levels in certain regions of the brain. The turnover of cerebrospinal fluid in these areas of the brain has been linked with flushing out amyloid-beta proteins from the brain back into the bloodstream. 

Though there are still many confounding factors that impede caffeine’s official introduction into the pharmaceutical market such as age, sex, liver health, metabolism, and diet, many studies are making strides to investigate this molecule’s potential beyond just an energy boosting beverage. We appear to be well versed in its short term effects which include increased alertness, higher blood pressure, and increased need to urinate, but we have only begun to dig into its long term effects. Caffeine has become a daily part of most people’s lives, whether it be through a morning cup of coffee, afternoon tea, or a chocolate-y dessert. Yet, despite our long history with the chemical, dating as far back as the 9th century in Ethiopia, and its global omnipresence, our knowledge of the chemical in the medicinal area appears to still be incomplete as we are still discovering new potential uses for 1,3,7- Trimethylxanthine.

References

Stay up-to-date on news and publications: