Coffee beans, caffeine, unsplash, photo by Mike Keneally @asthetik

Since writing my article praising coffee in February during a honeymoon phase, I spent much of this year learning about coffee and caffeine as it exists in reality, and not through a lens of confirmation bias or wishful thinking. Like almost any plant, there are potentially positive benefits, some poisonous and detrimental effects, and some ambiguity of yet undiscovered mechanisms and compounds within them. The scientists researching coffee are drinking it while doing their work, and the journalists writing about the health benefits of coffee are sipping it while they type. Sometimes we have to detach from cultural bias and try to look at things as they are. In this case, to criticize and carefully review risks. To understand some of what caffeine is doing, we must first know a bit about adenosine and its relationship to caffeine.

Adenosine is a chemical with multiple roles in the body. Adenosine functions as a potent endogenous anti-inflammatory agent (Hasko and Cronstein, 2013), protecting us from the damage resulting from immune system activation. It is similar to GABA, as both are inhibitory neurotransmitters, opposing the excitatory transmitters like glutamate and aspartate. A deficiency of adenosine and GABA and an excess of glutamate are observed in schizophrenia, autism, anxiety, epilepsy, bipolar disorder, and some depressive and neurodegenerative conditions. About 32% of treatment-resistant epileptics achieve lifetime remission, or severe reduction in seizures, by eating a ketogenic diet, and a central mechanism for this is ketosis increasing brain adenosine, which inhibits the overexcitation that leads to seizures, and by opposing the DNA hypermethylation that encourages seizures, and is what eventually “locks” the brain into a perpetually hyperexcitability-state, causing treatment-resistance (Chen, et al., 2019).

Adenosine is crucial in the regulatory process of the stress and immune responses, because all inflammation causes a cellular release of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and other nucleotides, which cascades into what we know as the immune response. These nucleotides must be metabolized into adenosine which effectively ends the inflammatory response. When this step in the process is impaired, for example by caffeine, adenosine’s actions are necessarily reduced or blocked, and thus so would be our body’s ability to manage inflammation (Hasko and Cronstein, 2013).

Adenosine is an important in hair growth and regeneration, stimulating hair follicle expression of growth factors and beta-catenin (Oura, et al., 2008; Hwang, et al., 2012). Caffeine thus could cause or increase the likeliness of hair loss. Cortisol itself does this, so caffeine-induced cortisol release combined with the inability of adenosine to initiate hair growth is a double whammy against hair follicle health.

Coffee inhibits wound healing purportedly by blocking adenosine’s wound-healing functions (Ojeh, et al., 2016). A dire implication of this is that, since daily coffee intake is essentially a constant “topical” treatment of coffee along the intestinal lining, it inhibits our intestine’s maintenance repair processes, leading the way to long-term damage, cumulative intestinal permeability, and thus a host of diseases. Coffee directly impairs the intestinal mucosal barrier; one study found habitual coffee drinkers had a significantly leakier gut compared to non-coffee drinkers, but just 48 hours of abstinence is enough for significant gastroduodenal mucosa regeneration (Cibicková, et al., 2004). If you are going to use coffee, these discoveries would make cycling or occasional breaks imperative.

Sleep quality depends in part on adenosine. Research found that 200mg caffeine (~1.5 cups of coffee) consumed at 7 a.m. was enough to significantly harm sleep quality and reduce sleep amount when going to bed at 11 p.m. that night. Over 16 hours later, even though only a minuscule amount of caffeine remains in the system (here it was 17mumol/l at 8 a.m. compared to 3mumol/l at 11 p.m., a 140% decrease), it was enough to impair both nonREM and REM sleep. It’s postulated that if caffeine in the system during sleep isn’t to blame, then it’s the ability of caffeine during the day to impair our body’s natural preparation for sleep that night (Landolt, et al., 1995). Again, a chronically impaired quality in sleep, another maintenance repair process, will cause long-term problems. Occasionally cycling off caffeine would allow for some repair and restorative sleep, but there is no escaping the physiological harm that occurs when sleep is impaired for even just two days in a row. The buildup of amyloid-beta plaque, which is greatly increased by sleep debt, is seen in Alzheimer’s Disease (Kang, et al., 2009).

Caffeine can be seen as the anti-spirituality drug, or the anti-presence drug. The caffeinated state is antithetical to mindfulness, prioritizing sympathetic nervous system reactivity (“fight-or-flight”) over a relaxed state. Everything is evaluated more aggressively under the influence of caffeine. Adrenaline doesn’t enhance mood; it just amplifies whatever stimuli the organism is under. Therefore, any situational stress experienced under the influence of caffeine is more damaging than otherwise, just as caffeine or adrenaline can enhance motivation and excitement. Even the cortisol released when taking an exam is drastically higher vs. taking the exam without the caffeine (Lovallo, et al., 2006), so we can extrapolate that susceptible individuals suffer the effects of hypercortisolism, or subclinical Cushing’s syndrome, perhaps solely due to their caffeine use, and never realize it.

In psychiatric studies, schizophrenic patients who drank coffee had significantly increased thought-disorder symptoms (unusual thought content, euphoria-activation, and ratings of mania and psychosis) and cortisol levels compared to those who abstained from coffee (Koczapski, et al., 1989; Lucas, et al., 1990). In the 1990 study, the dose was 10mg/kg, which is obviously too much at once, so the takeaway is simply that psychiatrically susceptible individuals need to be very careful about amounts and spacing out their caffeine consumption, but the dose being large in this study doesn’t mean that schizophrenics drinking “safe” amounts of coffee around the world aren’t having their symptoms exacerbated by it. Cortisol released in response to stressors is likely to play a role in the development of psychosis, but even when external stressors were factored out in a sample of 219 patients, caffeine was a positive predictor of hallucinations (Jones and Fernyhough, 2009).

Caffeine inhibits neurogenesis (the growth of new brain cells) which impairs learning and encourages depression (Wentz and Magavi, 2009). Reduced neurogenesis occurs in aging, stress, and sleep deprivation, all factors that indicate a breaking down of our physiological state. Short-term, e.g. 1-day consumption of caffeine didn’t harm neurogenesis, but the long-term survival of neurons that developed under the presence of caffeine have a lower survival rate than typical neurons.

The exercise-induced increase in brain-derived neurotrophic factor (BDNF) is largely responsible for the mental benefits of exercise, but caffeine seems to blunt or inhibit this increase (Mesquita, et al., 2018).

Another major mechanism by which exercise enhances brain function is through increased blood flow to the brain. Caffeine, producing cerebral vasoconstriction (again, by blocking adenosine) reduces brain blood flow by an average of 27%. The researchers who discovered this found that the adenosine system was unable to adapt to compensate for this reduced brain circulation (Addicott, et al., 2009).

Caffeine inhibits the absorption of and depletes calcium, magnesium, zinc, iron, and the B-vitamins (Morck, et al., 1983; Ulvik, et al., 2008). The urinary excretion of calcium and magnesium continues into the next day from the caffeine consumed the day before (Kynast-Gales and Massey, 1994), and reabsorption of calcium and magnesium remains significantly reduced for an extended period (Bergman, et al., 1990). The consequences of deficiency of any of these nutrients are dangerous and can lead quickly to depression, fatigue, weakness, dizziness, headaches, and progress into clinical territory with permanent brain or organ damage, or death. Without caffeine, even just situational stress like loud noise depletes magnesium (Mocci, et al., 2001), so the aforementioned principle applies that caffeine, in addition to its own dehydrating and diuretic effects, will amplify stress-induced magnesium depletion.

Any substance we ingest can be used for positive outcomes, and even I have to credit coffee as assisting me in some achievements, or acting as a launching-tool to increase motivation and help initiate action. The caveat with any substance like this, though, is to view it as a supplement, and use it alongside a holistic foundation; not to become dependent upon or entwined with it to the point that it’s negative consequences outweigh its benefits. Our culture and minds romanticize coffee, it being a social drug, bringing people together and being a source of comfort and warmth. There is a genuine aspect to this but also a deliberately marketed corporate one. The coffee bean and caffeine are from Mother Nature; humans have admirably seized and harnessed them for our prerogative, but it is still a drug and should be respected as such.

Coffee for writing and blogging, caffeine, unsplash, photo by Andrew Neel @andrewtneel

Works Cited

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