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Coffee and Your Brain, College

Coffee doesn’t give you energy

Coffee makes people feel awake, yet the caffeine in coffee gives the body no energy. While you are awake, a molecule called adenosine builds up in your brain and tells you that you are tired. Caffeine sits in adenosine’s spots on brain cells and blocks that tired message for a while.

A 3D ball-and-stick model of the adenosine molecule
Your adenoids, at the top of your throat, carry the same aden- root.

Your word of the day is

uh-DEN-uh-seen

aden-glandfrom Greek adḗn
-os-a kind of sugarfrom German Ribose
-inean ending for chemical namesfrom Latin -ina

A molecule found in all living cells. In the brain, adenosine builds up while you’re awake and helps signal that you’re tired.

A young woman sleeping on a white pillow at night

The study below gave adults 400 mg of caffeine 6 hours before bed and measured their sleep with a headband monitor. Make your guess before you read the paper, and give your reason in one sentence.

How many minutes of sleep do you think 400 mg of caffeine, taken 6 hours before bed, cost compared with a placebo night?

Hint

In adults, half of a caffeine dose leaves the body every 3 to 7 hours. How much of the dose would still be in the body at bedtime?

White capsules in a black bowl on a marble counter

Read the paper

Drake, Roehrs, Shambroom and Roth, “Caffeine effects on sleep taken 0, 3, or 6 hours before going to bed,” Journal of Clinical Sleep Medicine, 2013. The paper is free to read.

Twelve healthy adults, ages 19 to 48, who regularly use caffeine slept at home for four test nights. On each test day they swallowed three pills, at 6, 3 and 0 hours before their usual bedtime. On three of the nights, one pill held 400 mg of caffeine and the other two were placebos. On the fourth night, all three pills were placebos. Neither the participants nor the researchers knew which pill held caffeine. Each morning, participants recorded their sleep in a diary (Table 2 of the paper), and a headband monitor that records brain waves measured their sleep each night (Table 3). The table below gives the mean total sleep time from both tables.

ConditionDiary total sleep, Table 2 (hours)Monitor total sleep, Table 3 (hours)Monitor sleep lost compared with placebo (minutes)
Placebo7.827.680
Caffeine at bedtime6.926.60
Caffeine 3 hours before bed6.776.54
Caffeine 6 hours before bed7.136.50
An old analog alarm clock in warm, low light

Fill in the last column of the table. Subtract each caffeine row from placebo, then multiply by 60. In Table 3, all three caffeine nights differed from placebo (p < 0.05).

In Table 3 of the Drake paper, caffeine taken at bedtime (6.60 hours of sleep) cost ____ of sleep compared with placebo (7.68 hours).

See the table
ConditionDiary total sleep, Table 2 (hours)Monitor total sleep, Table 3 (hours)Monitor sleep lost compared with placebo (minutes)
Placebo7.827.680
Caffeine at bedtime6.926.60
Caffeine 3 hours before bed6.776.54
Caffeine 6 hours before bed7.136.50
A steaming mug of coffee on a wooden coaster outdoors

In Table 3 of the Drake paper, caffeine taken 3 hours before bed (6.54 hours of sleep) cost ____ of sleep compared with placebo (7.68 hours).

See the table
ConditionDiary total sleep, Table 2 (hours)Monitor total sleep, Table 3 (hours)Monitor sleep lost compared with placebo (minutes)
Placebo7.827.680
Caffeine at bedtime6.926.60
Caffeine 3 hours before bed6.776.54
Caffeine 6 hours before bed7.136.50
A steaming cup of coffee on a table in a sunny café

In Table 3 of the Drake paper, caffeine taken 6 hours before bed (6.50 hours of sleep) cost ____ of sleep compared with placebo (7.68 hours).

See the table
ConditionDiary total sleep, Table 2 (hours)Monitor total sleep, Table 3 (hours)Monitor sleep lost compared with placebo (minutes)
Placebo7.827.680
Caffeine at bedtime6.926.60
Caffeine 3 hours before bed6.776.54
Caffeine 6 hours before bed7.136.50
A man lying awake in bed in the early morning beside a clock showing 4:56 a.m.

In Table 3 of the Drake paper, did taking caffeine earlier in the evening shrink the sleep loss?

See the table
ConditionDiary total sleep, Table 2 (hours)Monitor total sleep, Table 3 (hours)Monitor sleep lost compared with placebo (minutes)
Placebo7.827.680
Caffeine at bedtime6.926.60
Caffeine 3 hours before bed6.776.54
Caffeine 6 hours before bed7.136.50
A woman writing in a notebook on a bed with polka-dot sheets

At 6 hours, the diaries showed 41 minutes of lost sleep (p = 0.08), and the monitor showed about 71 minutes.

Why might the sleep diaries and the headband monitor disagree for caffeine taken 6 hours before bed?

See the table
ConditionDiary total sleep, Table 2 (hours)Monitor total sleep, Table 3 (hours)Monitor sleep lost compared with placebo (minutes)
Placebo7.827.680
Caffeine at bedtime6.926.60
Caffeine 3 hours before bed6.776.54
Caffeine 6 hours before bed7.136.50
A white pill bottle spilling pink capsules onto a beige surface

Which features of the Drake study design make the monitor result more convincing?

See the table
ConditionDiary total sleep, Table 2 (hours)Monitor total sleep, Table 3 (hours)Monitor sleep lost compared with placebo (minutes)
Placebo7.827.680
Caffeine at bedtime6.926.60
Caffeine 3 hours before bed6.776.54
Caffeine 6 hours before bed7.136.50
A ball-and-stick model of the caffeine molecule

Caffeine is a purine alkaloid, and adenosine contains adenine, a purine base. Caffeine binds A1 and A2A adenosine receptors with roughly equal affinity without activating the receptors. In adults, caffeine’s half-life runs from 3 to 7 hours.

With a 5-hour half-life, about ____ of a 400 mg caffeine dose remains 6 hours later, at bedtime in the Drake study.

See the table
ConditionDiary total sleep, Table 2 (hours)Monitor total sleep, Table 3 (hours)Monitor sleep lost compared with placebo (minutes)
Placebo7.827.680
Caffeine at bedtime6.926.60
Caffeine 3 hours before bed6.776.54
Caffeine 6 hours before bed7.136.50
A space-filling model of the caffeine molecule, with carbon in black, hydrogen in white, oxygen in red and nitrogen in blue

Based on caffeine’s structure, why did about 174 mg of caffeine at bedtime still shorten sleep?

See the table
ConditionDiary total sleep, Table 2 (hours)Monitor total sleep, Table 3 (hours)Monitor sleep lost compared with placebo (minutes)
Placebo7.827.680
Caffeine at bedtime6.926.60
Caffeine 3 hours before bed6.776.54
Caffeine 6 hours before bed7.136.50
A ball-and-stick model of adenosine triphosphate (ATP), the molecule that carries energy in cells

Adenosine forms when brain cells break down ATP, the molecule that carries energy in cells.

Why does caffeine change how tired a person feels without adding energy to cells?

See the table
ConditionDiary total sleep, Table 2 (hours)Monitor total sleep, Table 3 (hours)Monitor sleep lost compared with placebo (minutes)
Placebo7.827.680
Caffeine at bedtime6.926.60
Caffeine 3 hours before bed6.776.54
Caffeine 6 hours before bed7.136.50
A ball-and-stick model of paraxanthine, the main breakdown product of caffeine

The liver breaks caffeine down mainly with the enzyme CYP1A2, and the main breakdown product is paraxanthine.

How could paraxanthine, caffeine’s main breakdown product, change how long caffeine’s effect lasts?

See the table
ConditionDiary total sleep, Table 2 (hours)Monitor total sleep, Table 3 (hours)Monitor sleep lost compared with placebo (minutes)
Placebo7.827.680
Caffeine at bedtime6.926.60
Caffeine 3 hours before bed6.776.54
Caffeine 6 hours before bed7.136.50
A steaming cup of coffee on a table indoors

Table 3 of the Drake paper reports the sleep the headband monitor measured on each night.

Which summary fits Table 3 of the Drake paper for caffeine taken 6 hours before bed?

Black-and-white photo of a tired man sitting in a kitchen, holding a coffee mug

Which question can’t Table 3 of the Drake paper answer?

Video looking down at hot coffee being poured into a mug on a table

Lesson complete

Today’s word

adenosine

uh-DEN-uh-seen

A nucleoside formed from the purine base adenine and the sugar ribose. In the brain, extracellular adenosine rises during waking and is proposed as a signal of sleep need.

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Sources
  1. Christopher Drake, Timothy Roehrs, John Shambroom and Thomas Roth, Henry Ford Hospital Sleep Disorders & Research Center in Detroit, Journal of Clinical Sleep Medicine, 2013
  2. Review by Carolin Reichert (University Psychiatric Clinics Basel), Tom Deboer (Leiden University Medical Center) and Hans-Peter Landolt (University of Zürich), Journal of Sleep Research, 2022
  3. Review by Jennifer Temple (University at Buffalo) with colleagues at Aix Marseille University and Wayne State University, Frontiers in Psychiatry, 2017
  4. D. Robertson, J. A. Oates and colleagues, New England Journal of Medicine, 1978
  5. J. P. DiMarco and the Adenosine for PSVT Study Group, led from the University of Virginia, Annals of Internal Medicine, 1990
  6. J. A. Nathanson, Science, 1984
  7. ChEBI records in PubChem, Caffeine and adenosine
  8. Vision and Change core concepts and competencies, as summarized in Brownell and others, CBE Life Sciences Education, 2014
  9. Emergency use of adenosine, Gebril and Hawes, Emergency Medicine Journal, 2012
  10. Word origins from Dictionary.com: adenosine, adenine, adeno-, ribose, arabinose, gum arabic, -ine, caffeine, coffee, adenoid, receptor, antagonist, antagonize
  11. Spanish and French spellings from Wiktionary
  12. Instagram original of the video, not linked because Instagram needs a login
  13. Transcript from the posted video on YouTube