Coffee and Your Brain

Watch

1. Coffee doesn’t give you energyyoutube.com/shorts/qIIaPqW8qkk

Word of the day

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.

• Your adenoids, at the top of your throat, carry the same aden- root.
• Caffeine has the same -ine ending. Its name comes from café, the French word for coffee.

Bonus word. Antagonist (from the Greek antagōnízesthai, “to contend against”) describes a substance that interferes with the action of another substance, especially by binding and blocking its receptor. Caffeine is an adenosine receptor antagonist.

Predict

1. 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?

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.

1. Quantitative reasoning 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). How many minutes of sleep did caffeine cost at each time? Did taking caffeine earlier in the evening shrink the loss?

   Hint. Compare your three answers with one another, then with 60 minutes.

2. Process of science In the diaries, caffeine taken 6 hours before bed cut sleep by 41 minutes, a difference that was not statistically significant (p = 0.08). The monitor showed a larger loss on the same nights. Why might the diary and the monitor disagree at 6 hours? Which features of the study design make the monitor result more convincing?

   Hint. Think about what a sleeping person can notice. Then look at the pills, the placebo night and who knew which pill held caffeine.

3. Structure and function 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. Use a 5-hour half-life. About how much of the 400 mg dose remained at bedtime in the 6-hour condition? How does caffeine’s structure explain why that amount still shortened sleep?

   Hint. Remaining caffeine = 400 × (1/2)^(6 ÷ 5). Then think about what the adenosine that accumulated during the day can do at a blocked receptor.

4. Pathways and transformations of energy and matter Adenosine forms when brain cells break down ATP, the molecule that carries energy in cells. The liver breaks caffeine down mainly with the enzyme CYP1A2. Caffeine’s main breakdown product, paraxanthine, also binds A1 and A2A receptors in animal studies. Why does caffeine change how tired a person feels without adding energy to cells? How could paraxanthine change how long caffeine’s effect lasts?

   Hint. Follow the matter. Where does adenosine come from, and what does the liver turn caffeine into?

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