Coffee and Caffeine

Enjoy your filtered coffee and caffeine in moderation.

Caffeine is “the most widely consumed psychoactive agent” worldwide due to its presence in coffee and tea – the two most globally popular beverages. It seems almost universal in healthcare, especially in training, that caffeine is intentionally consumed for optimized performance when fatigued. And yet, despite its widespread use and abuse, we often know little about the consequences and nuances of long term use except for what we have learned from experience. The New England Journal of Medicine recently published an excellent review article titled “Coffee, Caffeine, and Health” that summarizes what we know about caffeine and coffee from research. I have included a brief review of the salient points below supplemented by data from Tintinalli’s.


  • Coffee is the primary source of caffeine for adults in the United States. Other common caffeine sources include soft drinks, tea, energy drinks, and chocolate.
  • The majority of American adults ingest caffeine daily at an average of 135mg per day.
  • In addition to caffeine, coffee also “contains hundreds of other biologically active phytochemicals” that may “reduce oxidative stress, improve the gut microbiome, and modulate glucose and fat metabolism.”
Caffeine SourceDose
Coffee (8 oz, Coffee Shop)157 mg
Coffee (8 oz, Brewed)92 mg
Espresso (1 oz)63 mg
Black Tea (8 oz)47 mg
Green Tea (8 oz)28 mg
Soda (8 oz)21 mg
Dark Chocolate (1 oz)24 mg
Milk Chocolate (1 oz)6 mg


  • Caffeine is a methylxanthine, an alkaloid that behaves as a mild psychoactive stimulant by antagonizing adenosine receptors in the brain. Adenosine decreases arousal and increases drowsiness, so by blocking these effects, caffeine produces the opposite effect. Caffeine also provokes the release of endogenous epinephrine and norepinephrine which subsequently stimulate B1 and B2 adrenergic receptors. At toxic levels, caffeine also inhibits phosphodiesterase thus increasing cyclic AMP and amplifying the catecholamine effects.

Except at extreme levels of consumption and overdose…caffeine is very well tolerated when consumed regularly and at moderate levels.

  • Caffeine toxicity can occur at very high levels of consumption, typically >1200 mg. Side effects include “anxiety, restlessness, nervousness, dysphoria, insomnia, excitement, psychomotor agitation, and rambling flow of thought and speech.” Consuming very large amounts of caffeine (>10 grams) can cause death due to sympathomimetic overload.
  • In one study, ingestion of 320mg of caffeine at one time caused acute but transient adverse effects including “increased blood pressure, prolonged QT interval corrected for heart rate, and palpitations.” But these effects were not experienced by those who limited their caffeine consumption to <200mg.
  • Regular consumption of caffeine leads to effect tolerance within approximately one week, and abrupt caffeine cessation after prolonged and consistent ingestion causes withdrawal symptoms within 1-2 days. Withdrawal symptoms can last 2-9 days and include “headaches, fatigue, decreased alertness, and depressed mood.”
  • Except at extreme levels of consumption and overdose as described above, caffeine is very well tolerated when consumed regularly and at moderate levels.
Absorptionwithin 45 minutes of ingestion
Peak Blood Levels15 – 120 minutes
Half-Life2.5 – 4.5 hours, but varies widely
Distributionwidely, throughout all tissues, crosses the blood-brain-barrier
Metabolismin the liver, cytochrome P-450 system
Excretionin the urine as uric acid
Toxicity>1200 mg
Death10-14 grams

Long Term Effects of Coffee/Caffeine

  • Studying the effects of caffeine and coffee separately is difficult, just as separating the effects of nicotine and tobacco is almost impossible, therefore the generalization of coffee/caffeine study results to other caffeinated beverages can be problematic. Other confounding variables in the literature include failures to account for smoking or “other unfavorable lifestyle factors,” measurement errors in reported coffee/caffeine ingestion, exposure miscalculations due to unreported coffee additives, and the complexities of separating the acute from chronic effects of caffeine.
  • Despite the difficulties involved in coffee/caffeine research, there is a growing body of evidence that when interpreted carefully casts the moderate consumption of coffee and caffeine in a favorable light.

There is a growing body of evidence that when interpreted carefully casts the moderate consumption of coffee and caffeine in a favorable light.

  • In the literature, there is no association between coffee/caffeine consumption and the increased risk of hypertension, atrial fibrillation, stroke or coronary artery disease. While unfiltered coffee does increase levels of Low Density Lipoprotein (LDL) cholesterol, filtered coffee does not cause this same effect.
  • In fact, coffee/caffeine consumption is associated with a reduced risk of diabetes, some cancers (skin, breast, prostate, endometrial, and hepatocellular carcinoma), gallstones and kidney stones, Parkinson’s disease, and depression and suicide.
  • Caffeine should be limited during pregnancy (<200mg/day) due to the association of low birth weight and pregnancy loss with high levels of caffeine consumption. This effect was not seen when caffeine ingestion was limited to lower levels.
  • “Consumption of 2 to 5 standard cups of coffee per day has been associated with reduced mortality in cohort studies across the world.” While the authors do not necessarily suggest only consuming coffee for the health benefit, they do agree that coffee consumption can be a part of a healthy lifestyle.
  • “Consumption of caffeinated coffee and consumption of decaffeinated coffee were associated with a reduced risk of death from any cause.” This is an interesting finding, suggesting that the other ingredients of coffee, and not only caffeine, confer a health benefit.

Consumption of 2 to 5 standard cups of coffee per day has been associated with reduced mortality in cohort studies across the world.

Coffee, Caffeine, and Health. NEJM.


As with any substance, overconsumption of caffeine can lead to acute toxicity and adverse effects. But the evidence that is currently available shows no significant associated harm with moderate levels (3-5 cups) of coffee/caffeine consumption in non-pregnant adults, and it actually demonstrates numerous associated health benefits.

The authors do suggest “limits of 400 mg of caffeine per day for adults who are not pregnant or lactating and 200 mg per day for pregnant and lactating women.”

So, enjoy your filtered coffee and caffeine…in moderation of course.


  1. van Dam RM, Hu FB, Willett WC. Coffee, Caffeine, and Health. N Engl J Med. 2020;383(4):369-378. doi:10.1056/NEJMra1816604
  2. Gresham C, Brooks DE. Methylxanthines and Nicotine. In: Tintinalli JE, Ma O, Yealy DM, Meckler GD, Stapczynski J, Cline DM, Thomas SH. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9e. McGraw-Hill; Accessed September 11, 2020.
  3. Francesco Bonetti, Gloria Brombo, Giovanni Zuliani, Chapter 19 – Nootropics, Functional Foods, and Dietary Patterns for Prevention of Cognitive Decline. Editor(s): Ronald Ross Watson, Nutrition and Functional Foods for Healthy Aging. Academic Press, 2017, Pages 211-232, ISBN 9780128053768,

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