The Second Wave

Most people judge a coffee by how it feels. Within half an hour you're sharper and more awake. A few hours later that's gone, and it feels as though the coffee has worn off. The feeling is real, and it's a poor guide to what's still in you. That gap is what this series is about.

We went looking into it because of chocolate. Our founder had noticed that chocolate in the evening kept him awake, and when he cut it out and then brought it back, the pattern held. That raised a question about his coffee. If evening chocolate could cost him sleep, what was his afternoon coffee still doing at bedtime, long after he'd stopped feeling it?

What a coffee feels like

Caffeine works fast. From a drink, it's at its highest in your blood about half an hour later, and in studies people can tell caffeine from a dummy pill within 10 to 30 minutes. Some people notice as little as 10 to 20 mg.

Around 100 mg, people report feeling more alert and energetic, in a better mood and less sleepy. More isn't better. From about 150 mg some people start to feel anxious, and at 450 to 500 mg most people who rarely drink caffeine feel anxious, tense and aware of their heartbeat.

The lift is also short. In one study, a small dose gave people more energy half an hour later and left them more tired an hour and a half later.

If you drink it every day

For a daily coffee drinker, most of what the morning cup feels like is relief from the mild withdrawal that sets in overnight. After a night without it you're a bit sleepier and duller than you'd otherwise be, and the coffee brings you back to normal. In a study of nearly 380 people, that's all it did for regular drinkers: it restored them to where people who never drink caffeine already were. Within about two weeks of daily caffeine, most of the other feelings fade too.

What keeps going after the feeling fades

The feeling comes and goes in a couple of hours, but the caffeine takes much longer to leave. Your liver turns about four in five caffeine molecules into a second stimulant called paraxanthine. It builds up for about five hours, and by ten and a half hours after the cup there's more of it in you than caffeine.

Paraxanthine is something you can feel. Taken on its own, our founder rated 50 mg of it at 3 out of 10 for felt strength, against 5.5 for 120 mg of caffeine. After a coffee, though, it arrives slowly, hours after the lift you notice, so it's easy not to think of it as part of the coffee at all.

Have a 200 mg coffee at 1 p.m. and by 11 p.m. you won't feel a thing. The model still has about 37 mg of caffeine and 35 mg of paraxanthine in you. Part 2 of this series is about what that does to your sleep, and whether you'd notice.

What to do tomorrow

Stop using the feeling as your sign that caffeine is gone. Decide when you want to be asleep and count back from there. If you drink coffee every day, the afternoon cup does less for how you feel than you'd think, because tolerance has taken most of its lift, and what it leaves in you at bedtime is the same as ever.

Health Canada's limit for healthy adults is 400 mg of caffeine a day, and 300 mg during pregnancy or breastfeeding.¹⁷ If you're pregnant or breastfeeding, take regular medication, or have a heart condition, the right amount and timing for you is a conversation with your doctor or pharmacist.

You feel a coffee for a couple of hours. It keeps working for most of a day.

How long a coffee lasts depends on whether you ask your body or your blood. Have 200 mg at 1 p.m. and you'll feel it by half past; by four you'd probably say it had worn off. Working from published clearance rates, about 37 mg of caffeine is still in you at 11 p.m., along with 35 mg of paraxanthine, a stimulant your liver makes out of caffeine. The felt part is the short one, tolerance shortens it further for daily drinkers, and the long part is what your sleep has to deal with.

What each dose feels like

The cleanest evidence on felt effects comes from people who rarely drink caffeine, because daily drinkers are tolerant and partly in withdrawal. In those studies:

• 10–56 mg: enough for some people to tell caffeine from a dummy pill. In a study of seven people, the lowest dose each could reliably detect was 10 mg for one, 18 mg for three and 56 mg for three, and they said they noticed it through changes in mood.¹ In a second study of 15, the lowest dose that produced both detection and mood changes ranged from 18 to 100 mg.²
• 100 mg: higher ratings of alertness, energy, well-being, concentration and motivation for work, and lower ratings of sleepiness.¹
• 150 mg: close to where anxiety starts. In 102 light users given 50, 150 or 450 mg, only 450 mg raised anxiety for the group, but people with one variant of the adenosine receptor gene were already more anxious at 150 mg.³
• 250 versus 500 mg: in 12 adults, 250 mg felt pleasant (elation, peacefulness). 500 mg added tension, nervousness, restlessness and palpitations, and helped performance less than 250 mg did.⁴

When you feel it, and when it stops

From a drink, caffeine reaches its highest blood level about 30 minutes later.⁵ People start telling it from a dummy pill within 10 to 30 minutes, which fits.¹² The felt lift doesn't last long. In one study, 80 mg in water raised energy at 30 minutes and then left people more tired and more muddled at 90 and 150 minutes.⁶ Past the first few hours, few studies ask people how they feel at all.

What tolerance takes away

If you drink caffeine daily, your baseline changes. A review of the research concluded that the lift regular users feel is almost entirely the reversal of withdrawal.⁷ Two large studies bear that out. In 369 people split by how much caffeine they normally drank, going without made regular drinkers sleepier and slower, and caffeine brought them back; in non-drinkers and light drinkers it reduced sleepiness but added enough anxiety and jitteriness to cancel the benefit.⁸ In 379 people, caffeine never raised alertness above the level of non-drinkers on a dummy pill.⁹ And when 16 regular drinkers took 400 mg a day for two weeks, they became completely tolerant on seven of eight felt measures, with no net benefit over taking none.¹⁰

So for a daily drinker, the first cup mostly repairs the morning, and the afternoon cup adds little you can feel. What each cup leaves in your body doesn't shrink with tolerance.

What's still working

Your liver turns about four-fifths of each caffeine dose into paraxanthine and about a tenth into theobromine.¹² Paraxanthine clears a little faster than caffeine (half-life 3.1 hours against 4.1), but it's made continuously as the caffeine breaks down, so its amount rises for about five hours and passes caffeine at about ten and a half.¹¹

Middle column from the studies above; the amounts are modeled (milligrams present), using measured half-lives and conversion rates.

Paraxanthine is a stimulant in its own right. Taken on its own, our founder rated 50 mg at 3 out of 10 for felt strength and 120 mg of caffeine at 5.5; one person, but consistent with small trials in which 200 mg improved attention and memory tests.¹⁶ Part 3 of this series covers how it feels as a supplement.

Your own numbers

People clear caffeine at very different speeds. In the half-life study it was 4.1 hours give or take 1.3, in six healthy young men.¹¹ Genes, pregnancy, oral contraceptives, liver health, smoking and many medications move it, mostly through one liver enzyme, CYP1A2, which handles about 95% of caffeine.¹⁴ A slower enzyme stretches the whole tail. Your felt response varies too, with tolerance and with gene variants.

What to change first

Stop timing caffeine by feel. Pick your bedtime and count back, because by the time a coffee has stopped feeling like anything, most of it is still in you. If you drink daily, the cup worth protecting is the first one, which restores you from withdrawal. A late one adds little you'll feel and the same load at bedtime.

Health Canada's limit for healthy adults is 400 mg of caffeine a day, and 300 mg during pregnancy or breastfeeding.¹⁷ If you're pregnant or breastfeeding, take regular medication, or have a heart condition, the right amount and timing for you is a conversation with your doctor or pharmacist.

The subjective effects of caffeine are fast, short and tolerance-prone. The pharmacology is slow, long and indifferent to tolerance. That mismatch is the whole problem with timing caffeine by feel: the signal people use to judge when a dose has "worn off" is gone hours before the drug and its active metabolite are.

The felt evidence, and its limits

What's missing is a felt time course that runs as long as the pharmacology. We found no study rating subjective alertness or jitteriness hourly for twelve hours after an ordinary dose.

The model behind the part you don't feel

One compartment, first-order kinetics, instantaneous absorption. For caffeine C, paraxanthine P and theobromine B, in milligrams:

dC/dt = −k_C·C dP/dt = f_P·r·k_C·C − k_P·P dB/dt = f_B·r·k_C·C − k_B·B k = ln 2 / t½ r = 180.16 / 194.19 = 0.928

which gives P(t) = f_P·r·D · k_C/(k_P − k_C) · (e^(−k_C·t) − e^(−k_P·t)), the same form for B, and a peak at t_max = ln(k_P/k_C)/(k_P − k_C). Half-lives 4.1 ± 1.3 h (caffeine), 3.1 ± 0.8 h (paraxanthine) and 7.2 ± 1.6 h (theobromine), measured in the same six men;¹¹ branch fractions 0.796 and 0.108, the whole-dose conversion measured at steady state in five volunteers.¹² The demethylation-only shares (0.839, 0.121) and an in-vitro CYP1A2 profile (0.815, 0.108) shift bedtime totals by under 3 mg.¹²¹³

Caffeine's clock

Because paraxanthine clears faster than it's formed (k_P > k_C), its elimination becomes formation-limited after the peak: it falls at caffeine's rate, and P/C climbs toward f_P·r·k_C/(k_P − k_C) ≈ 2.3. That's why a single paraxanthine-to-caffeine ratio a few hours after a dose tracks caffeine clearance well enough (r typically above 0.85, 78 subjects) to serve as a CYP1A2 test.¹⁵ It also means paraxanthine's short half-life doesn't protect a slow metaboliser. Moving caffeine's half-life from 2.8 to 5.4 to 8 h changes the 10-hour total from 61 to 98 to 120 mg while paraxanthine barely moves (35, 34, 29 mg); the caffeine column is what swings.¹¹¹⁴

Milligrams and feelings

The model predicts mass, and felt intensity isn't linear in mass: detection thresholds sit far below the doses that bring anxiety, and tolerance flattens the whole curve. There's no validated conversion between a milligram of caffeine, of paraxanthine and of theobromine, and this series doesn't invent one. The one direct comparison we have is our founder's own rating, not a trial: 50 mg of paraxanthine taken on its own felt like 3 out of 10, and 120 mg of caffeine felt like 5.5. Read linearly, which it shouldn't be, that's 0.060 felt points per milligram for paraxanthine against 0.046 for caffeine. It does show that paraxanthine, at a dose comparable to what a coffee leaves at bedtime, can be felt when it arrives all at once. Small sponsor-funded trials agree it's psychoactive: 200 mg improved several attention and memory measures in 13 adults.¹⁶

What would falsify it

Two predictions are checkable. Pharmacologically, timed saliva samples after a known dose should show paraxanthine peaking four to six hours in and overtaking caffeine by ten to twelve; if typical metabolisers don't show that, the parameters are wrong and every number here with them. Subjectively, a study rating felt alertness and jitteriness hourly for twelve hours against measured caffeine and paraxanthine would show whether the felt curve tracks caffeine alone, both compounds, or neither once tolerance is accounted for. If it tracks caffeine alone, the second wave matters for sleep, if at all, without ever being felt, and Part 2 is where that question gets tested.

Health Canada's limit for healthy adults is 400 mg of caffeine a day, and 300 mg during pregnancy or breastfeeding.¹⁷ If you're pregnant or breastfeeding, take regular medication, or have a heart condition, the right amount and timing for you is a conversation with your doctor or pharmacist.