The effects of caffeine consumption do not decay with a ~5 hour half-life

https://www.lesswrong.com/posts/vefsxkGWkEMmDcZ7v/the-effects-of-caffeine-consumption-do-not-decay-with-a-5

by swah • 3 months ago

101 105 3 months ago

lesswrong.com

uticus• 3 months ago

Importantly, the primary metabolites also block adenosine receptors.

Biochemistry is rarely a one-and-done event it would seem.

meitham• 3 months ago

I haven’t come across lesswrong before! Great site and this caffeine article is great presentation of data.

OuterVale2• 3 months ago

I feel it my due diligence to advise you that LessWrong is closely associated with the rationalists and all that comes with them. It is worth doing a tad of research into the rationalist community and Eliezer Yudkowsky before going too deep down the LessWrong rabbit hole. https://en.wikipedia.org/wiki/Rationalist_community

Zababa4• 3 months ago

the rationalists and all that comes with them.

What does that mean?

yehoshuapw• 3 months ago

Regardless of the community,

Harry Potter and the Methods of Rationality is worth a read.

https://hpmor.com/chapter/1

Or a listen: https://hpmorpodcast.com/?page_id=56

embwbam• 3 months ago

One can take many good ideas from less wrong, yudkowsky et al without adopting a rationalist identity. Sure, it attracted wackos and they made a cult or two. But that could happen to anyone!

drakonka• 3 months ago

I think it is already pretty widely recognized that caffeine can disrupt sleep taken even as early as 6 or 7 hours before bed. I usually don't drink coffee or caffeinated tea after 12 for this reason. Caffeine also has many other known benefits, possible beneficial effects on all-cause mortality, etc, and I'm not sure if we have any research showing the same benefits coming from paraxanthine. Seems like potentially a bit of a waste just to be able to get the stimulant effect a couple of hours closer to sleep time.

mapt2• 3 months ago

This is a distinct claim. Caffeine can disrupt sleep even 48 hours later, a little bit; It is traditionally modelled with an elimination half-life of 5 hours, meaning 1/2 effect at 5 hours, 1/4 effect at 10 hours, 1/8 effect at 15 hours, an exponential decay curve.

The claim being made is that due to cascading decay of a secondary metabolite that does a lot of the work producing the clinical effect, caffeine elimination is a much more linear, slow process that only reaches half effect at around 10 hours and 1/4 effect at 17 hours, 1/8 effect at 23 hours.

mememememememo2• 3 months ago

This may explain why cold turkey effects for me take 24h to start

malfist2• 3 months ago

Just because the halflife leaves a measurable amount in your system, doesn't mean that that amount is enough for measurable outcomes.

In your example, a 200 mg caffeine intake in the morning, least to 100mg at noon, 50mg at 5PM, 25mg at 10PM. Yes that means you still have 25mg of caffeine. But it's unlikely to have an outcome you can measure since it's below a minimum threshold.

1vuio0pswjnm7• 3 months ago

"Caffeine can disrupt sleep even 48 hours later, a little bit;"

The literature for AASM protocols suggests 41 hours without caffeine is enough to safely control for those potential effects

bensyverson4• 3 months ago

This article makes the case for paraxanthine supplements; 80% of caffeine is metabolized into paraxanthine anyway, and it turns out paraxanthine behaves a bit more like we (apparently wrongly) assume caffeine works.

But the real question is: does it taste as good as espresso?

ortusdux• 3 months ago

I'd imagine it would not be hard to breed/engineer a coffee plant that produces more paraxanthine than caffeine. The plants take 5 years to mature so getting a crop to market would take a while though.

nlitened• 3 months ago

does it taste as good as espresso?

Coffee is an acquired taste, I think. People conditions themselves to like the bitter taste of coffee over time. I remember hating the taste of coffee (or beer, for example) in childhood.

bensyverson4• 3 months ago

It's definitely an acquired taste. But an espresso doesn't have to be overwhelmingly bitter! It can be almost sweet if it's extracted well.

Xcelerate• 3 months ago

I’ve heard that bitterness affects children more intensely. So I wonder how much of it is an acquired taste vs bitterness just becoming “milder” over time.

nightski• 3 months ago

That is entirely dependent on your diet as a child. I know children that love bitter or sour/fermented foods. Not to mention they dislike things that are overly sweet.

I wouldn't be surprised if all tastes are essentially "acquired".

anarazel• 3 months ago

Weirdly enough, I loved coffee from the first time I tried it, at maybe 13. Even though, looking back, it must have been terrible coffee, it was at something vaguely model UN like thing our entire class went to in an overnight trip. Obviously not enough sleep was had. A vending machine (in the late 90s) provided coffee...

altairprime4• 3 months ago

I now like bitters and soda, and I didn’t like bitter as a kid, so I think there might also be shifts in favor of bitter unrelated to coffee. Perhaps the same thing that leads people to appreciate spicy or sour as experiences broaden.

em-bee• 3 months ago

but why? i have to add so much milk and sugar to mask the bitterness that, combined with the negative effects, i asked myself, why do i even bother? i might as well just drink hot milk with sugar instead. now i only drink coffee if i need the energy and waking effects and nothing else sugary is available, which happens once a year, at most.

coldtea• 3 months ago

Coffee is an acquired taste, I think

Billions all over the world managed to acquire it just fine.

If that's an acquired taste, I doubt 99% of drinks that aren't an acquired taste would do much better, assuming there's anything doing better than coffee to begin with.

Not even Cola and tea come close.

sfink• 3 months ago

Speak for yourself. The bitter taste is what I like. When I don't like a cup of coffee, it's always going to be for being too sour. (Which can be masked pretty well with milk or a substitute, mind.)

I agree with your main point, though. I hated coffee most of my life. Even the smell made me feel ill. At some point, I flipped. I've always liked tea, fwiw.

I guess I don't hate beer as much as I used to. Still don't like it, though. Maybe another few decades?

Sharlin• 3 months ago

I can understand espresso being drunk for many reasons, but none of them are "tasting good".

bensyverson4• 3 months ago

I actually envy you, because having my first truly good espresso was an experience I wish I could relive

0xbadcafebee2• 3 months ago

Cafes that care about their coffee can have very good tasting espresso, but cafes that don't care will produce burnt bitter water. There's also Cafecito, which is basically liquid crack.

m463• 3 months ago

I accustomed myself to drinking coffee black. Then decaf. And later I tried camomile tea.

I found the need I really needed satisfied was a warm cup of something to curl my hands around in the morning, and they all worked after I let them. ymmv.

hk__2• 3 months ago

But the real question is: does it taste as good as espresso?

I don’t know where you live, but in Italy it’s extremely difficult to find a good espresso; you must go in "specialty coffee" places to taste real coffee, as all the bars use cheap coffee that tastes burnt. Ironically, it’s a country that takes pride in its coffee "tradition" but doesn’t know what coffee tastes like. The experience is the same in France, without the "tradition" thing.

michaelcampbell• 3 months ago

This feels like a Gwern blog, or something he'd be interested in.

OuterVale2• 3 months ago

Gwern is active on LessWrong: https://www.lesswrong.com/users/gwern

blitzar• 3 months ago

Its like a 45 minute decay - Im not shaking the cup's shaking. I can quit anytime I want, I just dont want to.

NoiseBert69• 3 months ago

For me a coffee is more kind of a ritual addiction.

Xerox9213• 3 months ago

Making coffee is often the only part of my day that I have control over.

bilsbie• 3 months ago

I switched to cocoa. Replaces the ritual at least. I still miss the boost though.

fredgrott• 3 months ago

sight correction....caffeine impacts two neuron groups not just one!

Dopamine and Noradrenaline

For dopamine its the competitive for the adenosine part of the dopamine heretodimer....meaning it prevents adenosine from binding and closing the dopamine receptor....

I use the effect on both dopamine and noradrenaline to assist in controlling my ADHD via more herb based means....

But author is yes correct that the metabolism of caffeine in how it breaks down does make the half life of its effects longer than 5 hours...I combine my dose with green tea ECGC which gives me a good focus boost of 12-16 hours...

cjbgkagh• 3 months ago

There are some fairly common genes that can drastically effect the strength and duration of caffeine so your experience may vary. For me the effect is very strong and one cup lasts all day, even as a habitual consumer.

oasisbob• 3 months ago

Great point. I'm a fast metabolizer, it's highly individualized.

charles_f• 3 months ago

That's an interesting takes. I found it quite suspicious at first, especially because it doesn't present well the myths that it's trying to debunk: are we talking abouy caffeine half life or its effects; and is that 5h half life related to the metabolism of caffeine, or related to its effects.

It looks like pharmacokinetics (ie how long caffeine stays in blood) is what's been studied mostly, and that's where the 5h timeline is coming from. I couldn't find papers on the timeline of pharmacodynamics of caffeine (how long it has effects).

That's an interesting gap this article is underlining!

siliconc0w2• 3 months ago

Nicotine is also a nice alternative to coffee. I still drink coffee but past late morning I'll usually reach for nicotine because the effect is much shorter.

It also has neuro-protective effects if you're an older gentleman.

vrganj• 3 months ago

It's also cripplingly addictive. Ask me how I know.

unmole2• 3 months ago

It's also cripplingly addictive.

That very much depends on the medium. It's virtually impossible for a nicotine naive individual to get addicted to losenges or gum.

sph2• 3 months ago

I have smoked for 14 years and hated every second of it until I quit. Nicotine is not cripplingly addictive. Inhaling tobacco (or electronic cigarette) vapour by lung is crippingly addictive.

Years later, I replaced my ADHD medication with low-strength nicotine patches and I find it as effective, cheaper, longer-lasting and with less addictive potential than dexamphetamine. The side effects when I forget a patch are much less than not having my morning cup of coffee — just extremely distractable and lower energy.

Smoking is terrible, but I wish people learned that the effects of smoking are much more intense from the effects of pure nicotine.

siliconc0w2• 3 months ago

Maybe if you use the pouches but I rarely 'feel' like gum like I feel like a coffee.

If I'm on vacation I don't even think about having a gum. It's only when I'm working, notice I'm dragging, and remember the option.

annoyingnoob• 3 months ago

Why change what works? Especially if you enjoy it.

atlgator• 3 months ago

I generally avoid caffeine at all costs. I'm susceptible to SVT, and I want the Adenosine to work if I should need it. Caffeine blocks Adenosine receptors. But on the rare occasion I have a single can of caffeinated Diet Coke, I experience a crash 48 hours later so profound that I cannot get out of bed that day.

keepamovin3• 3 months ago

I take pentoxyfylline (a synthetic substituted xanthine, caffeine is a natural substituted xanthine) occasionally as a nootropic and supplement for vascular health and anecdotally for me it has several nice caffeine like properties without the jitters/ long tail, sleep effects etc.

I find the listed side effects don’t happen for me besides occasional flush/blush. Which at my age is more like youthful vigor.

Caffeine is is 1,3,7-trimethylxanthine, pentoxyfylline is 3,7-dimethyl-1-(5-oxohexyl)xanthine.

Good effects are: sustained mental clarity, focus and energy with a smoother more stable baseline than caffeine’s bursty performance; good sleep, but strangely you can also stay up, if you prefer; feeling similar to “after exercise”. Half life is listed as under 1 hour, but beneficial effects can be felt for half a day after 400mg (a standard dose). So maybe there’s something like metabolite dynamics occurring here too.

This ends my erowid/hive style “trip/nootropic” report ;)

ronjakoi• 3 months ago

You should start a xanthina where you serve various xanthinated beverages.

CableNinja• 3 months ago

Coukd call it... xanzi-bar

qingcharles• 3 months ago

Pentoxyfylline is prescription in the USA?

bookofjoe2• 3 months ago

Yes

quinncom• 3 months ago

Do you know how much it affects your deep sleep duration?

People who drink caffeine at night may claim to be able to sleep still, but they will find that deep sleep stages are shorter, which is significant because it may be the most important type of sleep.

bot403• 3 months ago

I never slept as bad in my life as when I had a single can of coca cola at 8-9 pm and went to bed at 11-12pm

I did this for a while working nights until I caught on. The nights I didn't have a can were much better.

keepamovin3• 3 months ago

Seems to enhance sleep.

georgewsinger• 3 months ago

I'm surprised the author didn't mention the other argument for paraxanthine being less addictive than caffeine: it has a less acute/peaky curve of adenosine blocking.

I'm not a biologist, but I'm under the impression that your body uses the heuristic of "the more acutely a neurotransmitter is suddenly flooded into our system, the more of a homeostatic counter-response we're going to launch in the form of things like dopamine downregulation (etc, depending upon what neurutransmitter we're talking about)".

I'm not entirely sure this is true, but it seems to be corroborated by other researchers (e.g. Anna Lembke in her book Dopamine Nation, which isn't about caffeine though).

This is why substances like theacrine claim to offer even less tolerance than paraxanthine: it has a super gradual adenosine-blocking curve, with super long half-life (like 12-16 hours, IIRC). So when you take one theacrine, you won't notice it for hours, but its effects will last longer than one day (though I forget what its interaction with sleep is supposed to be?).

sharpshadow• 3 months ago

Fun fact smoking reduces caffeine half-life up to 50% by upregulating the enzymes which break it down, which affect paraxanthine as well.

R_D_Olivaw• 3 months ago

Smoking in general? Tobacco specifically?

bembem_c• 3 months ago

Pharmacokinetics (in this case: half-life in the central(venous) compartment, totally neglecting the distribution to the site of primary activity, the CNS) is only half of the truth.

You have to consider pharmacodynamics: where is the site of action located, where are the receptors located. And how well do caffein and paraxanthine distribute to this compartment.

Soiler: Most metabolites are more hydrophilic than respective parent compounds (biological sense of metabolism: to increase renal clearance of xenobiotics). Therefore, receptor affinity alone tells you little about the relative contribution of any metabolite for the pharmacological effect observed.

And to complicate things even more: Long-half life metabolites are only ONE potential reason for prolonged biological effects.

mannyv• 3 months ago

FYI you can't patent a supplement. You can, however, be the only manufacturer because nobody else noticed it.

insane_dreamer• 3 months ago

I used to drink two double-espressos (technically a latte with a double-espresso in it) a day -- one in the morning, one early afternoon -- for many years.

~5 years ago I stopped drinking the afternoon coffee, and have subjectively noticed improvements in my sleep -- less wakeful in the night. It also fits better with my sleep habits, where when I was younger I commonly worked past midnight whereas now I'm asleep by 10 pm and wake up early.

I still drink the morning coffee and I wouldn't switch to another stimulant because the main reason I drink coffee is because I enjoy drinking coffee :)

borisyurkevich• 3 months ago

Caffeine++* actually uses the 5 hours as default, looks like I can make the formula more correct based on this article. *My app.

thenoblesunfish• 3 months ago

Very interesting! An aside and fishing lazily: I am one of those people where caffeine has a very strong and long lasting effect. I don't have caffeine after about 9am or it affects my sleep that night. I love drinking coffee, and fortunately for me it seems like decaf got way better and widely available recently. Did something happen there?

The effects of caffeine consumption do not decay with a ~5 hour half-life

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