14 ms·

Caffeine suppresses cerebral grey matter responses to chronic sleep restriction

202 points by danielskogly 2y ago

5F7bGnd6fWJ66xN 2y ago
Ease Up on the Espresso: If your sleep isn’t great lately, consider cutting back on the caffeine. Turns out, chugging coffee during sleep-deprived stints might shrink grey matter in parts of your brain. Not ideal if you’re trying to keep that brain in tip-top shape. Know Your Limits: Everyone’s different when it comes to coffee tolerance. This study found that how your brain reacts to caffeine can depend on your genes—specifically, something about adenosine receptors. So, pay attention to how much caffeine you can handle, especially when you’re short on shut-eye. Catch Those Zs: Don’t skimp on recovery sleep. After a brutal week, make sure to get some solid, uninterrupted sleep to bounce back. It helps counteract the rough effects of those sleepless nights and may even undo some of the caffeine-induced brain changes.
- Ancalagon 2y ago
  AI DETECTED
whjkh 2y ago
[dead]
hu3 2y ago
Am I wrong to conclude from the abstract that sleep deprivation + caffeine = reduction in grey matter? Abstract: > Evidence has shown that both sleep loss and daily caffeine intake can induce changes in grey matter (GM). Caffeine is frequently used to combat sleepiness and impaired performance caused by insufficient sleep. It is unclear (1) whether daily use of caffeine could prevent or exacerbate the GM alterations induced by 5-day sleep restriction (i.e. chronic sleep restriction, CSR), and (2) whether the potential impact on GM plasticity depends on individual differences in the availability of adenosine receptors, which are involved in mediating effects of caffeine on sleep and waking function. Thirty-six healthy adults participated in this double-blind, randomized, controlled study (age = 28.9 ± 5.2 y/; F:M = 15:21; habitual level of caffeine intake < 450 mg; 29 homozygous C/C allele carriers of rs5751876 of ADORA2A, an A2A adenosine receptor gene variant). Each participant underwent a 9-day laboratory visit consisting of one adaptation day, 2 baseline days (BL), 5-day sleep restriction (5 h time-in-bed), and a recovery day (REC) after an 8-h sleep opportunity. Nineteen participants received 300 mg caffeine in coffee through the 5 days of CSR (CAFF group), while 17 matched participants received decaffeinated coffee (DECAF group). We examined GM changes on the 2nd BL Day, 5th CSR Day, and REC Day using magnetic resonance imaging and voxel-based morphometry. Moreover, we used positron emission tomography with [18F]-CPFPX to quantify the baseline availability of A1 adenosine receptors (A1R) and its relation to the GM plasticity. The results from the voxel-wise multimodal whole-brain analysis on the Jacobian-modulated T1-weighted images controlled for variances of cerebral blood flow indicated a significant interaction effect between caffeine and CSR in four brain regions: (a) right temporal-occipital region, (b) right dorsomedial prefrontal cortex (DmPFC), (c) left dorsolateral prefrontal cortex (DLPFC), and (d) right thalamus. The post-hoc analyses on the signal intensity of these GM clusters indicated that, compared to BL, GM on the CSR day was increased in the DECAF group in all clusters but decreased in the thalamus, DmPFC, and DLPFC in the CAFF group. Furthermore, lower baseline subcortical A1R availability predicted a larger GM reduction in the CAFF group after CSR of all brain regions except for the thalamus. In conclusion, our data suggest an adaptive GM upregulation after 5-day CSR, while concomitant use of caffeine instead leads to a GM reduction. The lack of consistent association with individual A1R availability may suggest that CSR and caffeine affect thalamic GM plasticity predominantly by a different mechanism. Future studies on the role of adenosine A2A receptors in CSR-induced GM plasticity are warranted.
- Strumpfli 2y ago
  That's what I concluded as well. What seems interesting is that sleep deprivation alone increased the GM, while combined with caffeine, the effect is reversed. Surprising, since I feel like the general impression on caffeine in media is that it does not harm the brain.
  - regularfry 2y ago
    My interpretation of that (especially over a short period like this) is that sleep restriction causes swelling in the grey matter, which caffeine reverses. Interpreted like that, caffeine would be protecting the brain, not harming it.
    - Terr_ 2y ago
      I think it's far too early to assume assume the "swelling" is a net harm or that preventing it is good in the long run. Perhaps it serves an important protective or regulatory purpose which we haven't yet identified, because we still know so little about sleep and consciousness. An analogy: There are lots of systems in your body that try to prevent and deter you from casually walking on a damaged leg, and we can override some of them with various external drugs, but that doesn't necessarily mean it's a good idea.
      - code51 2y ago
        So it very well could be that thinking on a worn neuron, trying to do memory access on it, might damage it even more (leg analogy)? It could be possible that the "swelling" could be redirecting brain to use other paths but with caffeine you're utilizing a worn-out neuron. Maybe with chronic deprivation + caffeine habit, you're weakening your cognitive function - repeatedly using a misfiring neuron. At least, with no caffeine, you'd feel your memory is hazy and hard to recall, go to sleep.
        Terr_ 2y ago
        IANANeuroscientist, but my idle-thought was that a lack of sleep could cause a buildup of waste byproducts, and structural adaptations might either reduce the effect of the buildup or else make its removal marginally easier.
redoubt 2y ago
Medical engineer here; I would suggest anyone whoms interest was caught by the title to read the Discussion, not Abstract. The authors have made good use of the section to broaden their conclusions, answering some of the questions I've observed in this thread. For anyone starting to second-guess their relationship to sleep and caffeine; do note that this is a small-sample study and that more research is needed before any conclusions can be drawn with regards to the population at large. EDIT: I'm not a medical professional (i.e a Doctor), I'm simply an engineer with domain knowledge in medicine. I am accustomed to reading studies like this. If anyone needs help interpreting the study, I'm happy to assist.
- iosguyryan 2y ago
  To pile on: it’s in Scientific Reports. Not high impact, not highest quality. It’s a 9 day in lab study on mystery taste lab brew coffee (whose brewing was deemed so insignificant to a coffee study that its brew recipe was excluded from the methods section). These sort of setups are useful from a “help me isolate some test cases” point of view, but is obviously as much a perturbation in participants natural lives that it might even outweigh the impact of drinking coffee. Further, it draws conclusions from an acute 5 day caffeine exposure, whereas in real life these participants relationships and adaptations to caffeine are built over a long period of time. The power of the study is small and not scoped for conclusions, but rather pointing to an area of interest for further funding.
- bovermyer 2y ago
  Thank you for this. I am not anywhere near to a medical professional and can't interpret these results correctly, I'm sure. It's good to have an experienced perspective.
  - redoubt 2y ago
    I'm happy you found it helpful, medical studies don't pop up all too frequently here at HN so I try to assist when confusion arises.
- deleted 2y ago
  [deleted]
bovermyer 2y ago
The important sentence from the abstract: > In conclusion, our data suggest an adaptive GM upregulation after 5-day CSR, while concomitant use of caffeine instead leads to a GM reduction. I'm not sure what to take away from that. It sounds bad, though.
vouaobrasil 2y ago
I like caffeine. It's fun to drink a cup of tea or coffee once in a while and feel an extra surge of productivity. What I don't like is that it has encouraged the grind of people working far longer and harder than they should for no reason except economic gain which is fundamnetally unsustainable. When people feel tired, they should take a break, and not develop a habit of drinking caffeine every day to keeep going. It's an unhealthy society and reinforces the message that economic gain is important above all else.
- velcrovan 2y ago
  I think people should be able to do what they want with their time. I don’t think people should have to sell their labor for a wage in order to live. I wonder what happens to your opinions about caffeine in a society where owners have little to no leverage over workers, or where the workers are generally also the owners.
  - sershe 2y ago
    > I wonder what happens to your opinions about caffeine Something like this: https://en.wikipedia.org/wiki/East_German_coffee_crisis https://en.wikipedia.org/wiki/East_German_coffee_crisis
  - mhb 2y ago
    What kind of tea do they serve in the gulag?
    - velcrovan 2y ago
      I dunno, ask the people who work at Mondragon. https://www.mondragon-corporation.com/en/about-us/ https://www.mondragon-corporation.com/en/about-us/
      - ta988 2y ago
        care to explain?
BossingAround 2y ago
Anyone with anxiety or sleep issues should reexamine their caffeine usage. Maybe those problems do not stem from caffeine, but maybe they do. I don't know many people that do not consume caffeine regularly, at least once a day - in such cases, you cannot know whether your anxiety, sleep problems, general tiredness, bad moods, ... are or are not caused by one's caffeine consumption. Some people swear by drinking a shot of espresso right after dinner, claiming that they can "sleep just fine" (or that it even calms them). It's not whether you can or cannot fall asleep, it's how deep and restorative your sleep is that is important here.
- fuzzfactor 2y ago
  One of the references in this paper focuses on single sleep deprivation events of a more extreme nature, 48 hours. As I have experienced when regularly (but not often) working a 36-hour day, I wouldn't do it if it wasn't proven to be well within reach, but it's no breeze if you are the least bit tired and not fully prepared beforehand, especially when it comes to nutrition and not having anything toxic in your system. This is completely different than regularly losing sleep every night in a habitual way, which could also be considered somewhat along the lines of everyday exposure to toxic materials, whether toxins enter the body intentionally or not. Don't ask me how I know what it feels like when exposure to different milligrams of different pure industrial chemicals having known toxicity occurs in spite of state-of-the art workplace controls and PPE. I've been working these truly chemical labs all my life. Eventually I felt like I was guinea-pigging caffeine too, and it's old as the hills. The default in many cultures is to be born into a caffeine-addicted society, steeped in excess habitual ritual in a way which encourages never-ending tradition. This is over and above the physical & emotional habit-forming nature of the drug itself. Anyway, culture can be real strong, and I enjoyed being a caffeine addict. It actually takes quite a bit of effort if you want to completely withdraw from its pervasive and widespread exposure, whether commercial influence is involved or not. It's everywhere. With everyday use you build up a tolerance like anything else, and in the long run it really doesn't make a difference whether you lose an hour of sleep every night or get an extra hour, you always feel the same and have the same energy so it must be working, right? Maybe that's supposed to be a red flag. Now when you're actually a pretty good addict, you never overdo it, you're never jittery or considered extreme like a 20-cup-a-day habit which can't be that bad either when so many of them seem to do just fine. But way below any extreme consumption, you can still end up with a fairly late-night dose which actually relaxes you and then you drop off to sleep like you habitually do. Actually without it you might be a little anxious otherwise. It's just your body calling out for what it needs to be normal, due to the current level of tolerance you have built up. Hey wait a minute, wasn't I enjoying this to begin with for it's stimulant effect? Too late, that effect has left the building. This is the part that leads studies like this to less-conclusive results. For me with nothing in the bloodstream almost ever any more (and after all the dust has settled), there's only slightly more energy than being a mainstream addict. I attribute it to the relatively small amount of toxic pressure exerted by the less-than-gram quantities of caffeine I was metabolizing. Yes, I have more energy without it in my system but it's not a miracle and I'm sure many people would not think it's worth it. It's not that toxic, believe me so many things are much worse. But when I need to go another 12 hours, one cup of coffee will do it. Never could be a consideration back when I had a tolerance, stronger stimulants wouldn't even help. Real sleep is the only answer then, you just can't push to the max whenever you really want when you're already strung out. One of the things that makes the 48-hour study more conclusive about usefulness best practices. This was their reference 3: http://scholar.google.com/scholar_lookup?&title=Randomized%2C%20double-blind%2C%20placebo-controlled%2C%20crossover%20study%20of%20the%20effects%20of%20repeated-dose%20caffeine%20on%20neurobehavioral%20performance%20during%2048%20h%20of%20total%20sleep%20deprivation&journal=Psychopharmacology&doi=10.1007%2Fs00213-018-5140-0&volume=236&issue=4&pages=1313-1322&publication_year=2019&author=Hansen%2CDA&author=Ramakrishnan%2CS&author=Satterfield%2CBC&author=Wesensten%2CNJ&author=Layton%2CME&author=Reifman%2CJ http://scholar.google.com/scholar_lookup?&title=Randomized%2...
janpmz 2y ago
Recently I've learned that half of the people are slow caffein metabolizers. The caffein stays longer in their system and it might negatively affect their sleep. Considering how many people drink coffee, I think a lot of people are affected by this.
- xen2xen1 2y ago
  Found that out the hard way twenty years ago. The stated half life is NOT for me what they say.
- b800h 2y ago
  Yep - raising my hand here. I've completely given up caffeine (including decaf, which isn't totally) because after I got a Fitbit, I realised that my morning coffee spiked my heart-rate to 120, and kept it thereabouts, slowly dropping to normal overnight, after which I'd start again. A genome sequence shows I'm a slow metaboliser (I expect more will show up with more research). I feel terrific now.
  - zemvpferreira 2y ago
    Slow metaboliser here. Also possibly more prone to caffeine addiction than most, according to said genome sequencing interpretation. I need to cap at 2 espressos per day before noon at most, or I start suffering side effects like poor sleep quality. People really need to reframe their coffee consumption from food to drug and understand their own usage and effects of said drug.
    - b800h 2y ago
      Please try quitting entirely. My cold turkey took a week and a half and involved intense muscle pain (going from drinking a coffee and a tea each day). I believe the caffeine was building up in my system, although I could be wrong. I strongly recommend Barleycup as an alternative morning cuppa.
      - zemvpferreira 2y ago
sir-dingleberry 2y ago
[flagged]
lemonlime0x3C33 2y ago
An interesting article to read, would love to see a larger samples size at some point. I am also going to continue drinking my mid-day espresso, morning coffee, and afternoon pick me up caffeine drink...
sir-dingleberry 2y ago
[flagged]
ilaksh 2y ago
I love my caffeine. But caffeine is an addictive, highly profitable substance. So advertising it and trying to promote it as somehow having real health benefits is widespread. I would not be surprised if routine consumption of caffeine was at least mildly detrimental to health. I think some drugs have managed to gain a special place in our society . Advertising and lobbying warps our perception of these drugs. I even saw a comment in this thread suggesting that if caffeine has a prolonged affect on you, then you have some unique genetics and it's essentially your problem, not the drug. Similar to the narrative about alcohol. It's interesting to compare that attitude to the way illegal drugs that can't advertise or lobby are viewed.
- 2OEH8eoCRo0 2y ago
  It's interesting that coffee (black) is essentially perfect (mostly pros, few or no cons) yet there is a small crowd bent on demonizing it.
- seoulmetro 2y ago
  >Advertising and lobbying warps our perception of these drugs. More like, our own preference and enjoyment of the drugs compared to their detriments constructs our perception of these drugs. Coffee, alcohol, pain killers, etc. These are all drugs that give the user enjoyment with very little down sides. This means that society has reserved a place for them.
- mensetmanusman 2y ago
  Alcohol reduces functions, caffeine clearly enhances functions. If caffeine was involved in nearly all violent crime like alcohol is, we would think differently of it.
  - m463 2y ago
    I think it is a matter of perception. For example, lots of DUI type accidents are blamed on alcohol, but it might actually be sleep deprivation that is the most fundamental cause of the accident. In a similar way, I wonder if similar sleep-related accidents or incidents could more properly have caffeine as a root cause (after it has worn off)
hereme888 2y ago
Caffeine, up to a certain daily dose, is associated with long-term cognitive benefits and a reduced risk of dementia. This study hints that it specifically doesn't benefit gray matter volume during periods of sleep restriction, at least in the short term. I wonder if substances like Ashwagandha extract or Magnesium L-threonate could mitigate gray matter loss during short term sleep restriction among caffeine drinkers.
- zemvpferreira 2y ago
  It seems more straightforward to simply curb caffeine consumption during periods where you're sleeping poorly. Most people (myself included in the past) would drink more coffee when they sleep less. Grey matter aside, I think this is a very poor strategy. It will make next night's sleep even less effective. Better to drink less coffee, have a shitty day/week, and sleep more restoratively as soon as you can. Don't get in a doom loop voluntarily. Have caffeine only when you're feeling well rested.
- azinman2 2y ago
  Ashwagandha extract Can only be safely taken up to 3 months. It’s not a long term benefit. Magnesium affects your heart’s signaling, which can be problematic if too much. I’m curious why you asked about Ashwagandha ahd magnesium? They seem to be THE supplements du jour, which is a pretty weird concept. There is a lot of grift going on, and little recognition of the potential negative health impacts of both.
  - hereme888 2y ago
    I asked specifically about Magnesium L-threonate due to its ability to increase synaptic connectivity (yet to be conclusively reported in humans) and hence gray matter, and Ashwagandha due to its neuroprotective, neurotransmitter-preserving, and cortisol-lowering effects. I take magnesium daily, including the regular dose of Magnesium L-threonate, and my last CMP showed serum levels within range. Maybe super large medical doses beyond even those used for eclampsia would affect heart conduction, or those who take way more than what supplement bottles recommend. I'm not sure what studies have conclusively shown Ashwagandha to be safe only up to 3 months. I get most of my herbal data from Examine.com (PhD academics that analyze data), where they say: "Some case reports have suggested adverse effects such as rash or thyroid dysregulation may occur with ashwagandha use, but the same has not yet been observed by safety studies with larger samples.[38][39][35] Several case reports have also raised concerns regarding the rare occurrence of liver toxicity with ashwagandha use, but similarly, toxicity has not been observed in clinical safety trials. In the reports, liver toxicity was usually reported within 2–12 weeks of ashwagandha use, and liver function returned to normal in all but one case following medical support and ashwagandha discontinuation.[40][41][42][43][44][45] An in vitro study suggested that withanone (one type of withanolide in ashwagandha), may have toxic effects in the context of low levels of the cellular antioxidant glutathione (GSH), which is involved in drug detoxification.[46] However, this research is far from conclusive and the mechanisms underlying this possible adverse effect are unclear."
marcodiego 2y ago
Rule: if you drink (coffee) dot not stay awake.
- deleted 2y ago
  [deleted]
iamleppert 2y ago
I've sad it before, and I'll say it again: the human body is not meant to ingest any other liquid than pure, filtered water.
- thebruce87m 2y ago
  Maybe you should stop saying it? When we are born we 1) don’t have a filter installed and 2) drink milk.
- whamlastxmas 2y ago
  Breast milk and the million sources of liquid in the foods we eat disagrees
andro_dev 2y ago
Caffeine does nothing for me at all, I do not get a kick when I drink coffee. It does not affect my sleep, it does not give me a boost at all. So I am a bit of jealous of those who can utilize caffeine for mental boost, I just drink it for the taste.
- maipen 2y ago
  I used to say the same thing until I tried different types of coffee and different amounts. The average expresso doesn't do much. Also if you are already feeling well, it's unlikely you will feel a big difference unless you consume a high dosage of caffeine, which can also cause you some anxiety. Caffeine is great when we are feeling low energy or sleepy.
  - thebruce87m 2y ago
    What specifically do you recommend trying? I don’t seem to get any physical symptoms after a coffee but my wife is the complete opposite.
  - andro_dev 2y ago
    Thanks I will try higher dosage.
taeric 2y ago
I am growingly convinced that coffee/caffeine hit people in very different ways. https://www.23andme.com/topics/wellness/caffeine-consumption/ https://www.23andme.com/topics/wellness/caffeine-consumption... has a few fun citations to look through on this, but discussions of how varied we are with how it impacts us is ridiculously invisible in most discussions of it. Sleep is similar. We speak of "night owls" and such, but most discussion around the varied needs of sleep are age targeted. With most discussion on how we should let kids sleep longer.
- claytongulick 2y ago
  I'm one of those. I have this super weird thing where I'm hyper-sensitive to caffeine, and its effects will hit me sometimes 6+ hours later. If I have a cup of coffee in the late morning, it will keep me up most of the night, and a single cup of coffee will make me manic-ish. People have (doctors included) told me that what I was experiencing was impossible, that caffeine in metabolized in a certain way and completely out of your system quickly. Turns out, that's true with most people, unless you have a variant in the CYP1A2 gene, which can cause the effects I experience.
lanstin 2y ago
On a cultural note regarding the threads, the moralistic make do with what god gives you side and the yay drink coffee and do stuff and be happy side have been around a long time. A little Bach Cantata about a grumpy old dad and his coffee drinking daughter: https://youtu.be/nifUBDgPhl4?feature=shared https://youtu.be/nifUBDgPhl4?feature=shared
sandworm101 2y ago
>> Each participant underwent a 9-day laboratory visit consisting of one adaptation day, 2 baseline days (BL), 5-day sleep restriction (5 h time-in-bed), and a recovery day (REC) after an 8-h sleep opportunity. Was this a vacation? Was this study done at a resort? During push times I aspire to 5-hour sleep times. Talk to anyone in any branch of the military. During any sort of active operation, 5-hours in bed is total luxury. Or fishers. Or cops. Or food service workers. Or doctors.
EZ-E 2y ago
Side topic, but dropping coffee was the best thing I ever did. I used to drink only one cup a day, rarely two, for many years - but turns out when I stopped (for reasons unrelated) my anxiety unexpectedly 80% went away after a week or so without any other changes in my lifestyle. It was a big difference and I feel now very different than what I used to. I wake up much better rested too (much easier to get out of bed). Too bad, I really loved the taste but it's not worth it for me. I encourage anyone to give it a try a few weeks and see how they feel. You may not realize what you thought is your baseline is in fact caused by caffeine sensitivity. I heard of some people being sensitive to caffeine but I never thought it would affect me, after all I did not have that bad of a reaction but it really built up and I had gotten used to it.
- obruchez 2y ago
  I've been suffering of anxiety for decades. Nothing really serious. I stopped caffeine for one month in 2022, cold turkey. No coffee. No tea. No chocolate. I stopped alcohol as well (I don't drink much, so it wasn't really hard). I track a lot of things daily and during this abstinence period, my anxiety didn't decrease. On the contrary, it (very slightly) increased. This, of course, was not a controlled/blinded experiment, the duration was rather short (1 month), N=1, and I actually did two experiments at the same time (caffeine + alcohol), which is not optimal. In summary, my conclusion is that I prefer drinking coffee (max 2-3 small cups daily, in the morning) than not. Still, I'd like to try the experiment again in the future and stop caffeine for a longer period this time (3 months?). Edit: I'm a slow metabolizer (rs762551 = AC).
- curmudgeon22 2y ago
  I've had a very similar experience. If i drink coffee daily, it bumps my anxiety significantly after a few days or a week. If i rarely have it, it's usually fine. But if I let myself have it, it's too easy to trend towards daily again. I drank coffee for years and don't think it had an impact, but at some point, I noticed it and the impact was very real when not drinking it.
- amirbehzad 2y ago
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amirbehzad 2y ago
[dead]
broguinn 2y ago
I haven't seen this mentioned in the comments yet, so I'll mention it here. For the last year, I've seen health pundits (Huberman, etc.) recommend delaying caffeine intake for two hours after waking, for the purpose of allowing adenosine to clear from the brain first. Ever since I've adopted this strategy, I find myself avoiding a mid-morning crash, and generally feeling more alert in the mornings. I wonder if the deleterious impact on grey matter could be mitigated in part by delaying consumption until fully awake.
ninininino 2y ago
Are any of these results applicable to a non sleep-restricted state? The study was on 5 days of 5-hr sleep only. How does caffeine affect 8-hrs sleep?

202 points by danielskogly 2y ago

Ease Up on the Espresso: If your sleep isn’t great lately, consider cutting back on the caffeine. Turns out, chugging coffee during sleep-deprived stints might shrink grey matter in parts of your brain. Not ideal if you’re trying to keep that brain in tip-top shape. Know Your Limits: Everyone’s different when it comes to coffee tolerance. This study found that how your brain reacts to caffeine can depend on your genes—specifically, something about adenosine receptors. So, pay attention to how much caffeine you can handle, especially when you’re short on shut-eye. Catch Those Zs: Don’t skimp on recovery sleep. After a brutal week, make sure to get some solid, uninterrupted sleep to bounce back. It helps counteract the rough effects of those sleepless nights and may even undo some of the caffeine-induced brain changes.

Ancalagon 2y ago
AI DETECTED

whjkh 2y ago

[dead]

hu3 2y ago

Am I wrong to conclude from the abstract that sleep deprivation + caffeine = reduction in grey matter? Abstract: > Evidence has shown that both sleep loss and daily caffeine intake can induce changes in grey matter (GM). Caffeine is frequently used to combat sleepiness and impaired performance caused by insufficient sleep. It is unclear (1) whether daily use of caffeine could prevent or exacerbate the GM alterations induced by 5-day sleep restriction (i.e. chronic sleep restriction, CSR), and (2) whether the potential impact on GM plasticity depends on individual differences in the availability of adenosine receptors, which are involved in mediating effects of caffeine on sleep and waking function. Thirty-six healthy adults participated in this double-blind, randomized, controlled study (age = 28.9 ± 5.2 y/; F:M = 15:21; habitual level of caffeine intake < 450 mg; 29 homozygous C/C allele carriers of rs5751876 of ADORA2A, an A2A adenosine receptor gene variant). Each participant underwent a 9-day laboratory visit consisting of one adaptation day, 2 baseline days (BL), 5-day sleep restriction (5 h time-in-bed), and a recovery day (REC) after an 8-h sleep opportunity. Nineteen participants received 300 mg caffeine in coffee through the 5 days of CSR (CAFF group), while 17 matched participants received decaffeinated coffee (DECAF group). We examined GM changes on the 2nd BL Day, 5th CSR Day, and REC Day using magnetic resonance imaging and voxel-based morphometry. Moreover, we used positron emission tomography with [18F]-CPFPX to quantify the baseline availability of A1 adenosine receptors (A1R) and its relation to the GM plasticity. The results from the voxel-wise multimodal whole-brain analysis on the Jacobian-modulated T1-weighted images controlled for variances of cerebral blood flow indicated a significant interaction effect between caffeine and CSR in four brain regions: (a) right temporal-occipital region, (b) right dorsomedial prefrontal cortex (DmPFC), (c) left dorsolateral prefrontal cortex (DLPFC), and (d) right thalamus. The post-hoc analyses on the signal intensity of these GM clusters indicated that, compared to BL, GM on the CSR day was increased in the DECAF group in all clusters but decreased in the thalamus, DmPFC, and DLPFC in the CAFF group. Furthermore, lower baseline subcortical A1R availability predicted a larger GM reduction in the CAFF group after CSR of all brain regions except for the thalamus. In conclusion, our data suggest an adaptive GM upregulation after 5-day CSR, while concomitant use of caffeine instead leads to a GM reduction. The lack of consistent association with individual A1R availability may suggest that CSR and caffeine affect thalamic GM plasticity predominantly by a different mechanism. Future studies on the role of adenosine A2A receptors in CSR-induced GM plasticity are warranted.

Strumpfli 2y ago
That's what I concluded as well. What seems interesting is that sleep deprivation alone increased the GM, while combined with caffeine, the effect is reversed. Surprising, since I feel like the general impression on caffeine in media is that it does not harm the brain.
- regularfry 2y ago
  My interpretation of that (especially over a short period like this) is that sleep restriction causes swelling in the grey matter, which caffeine reverses. Interpreted like that, caffeine would be protecting the brain, not harming it.
  - Terr_ 2y ago
    I think it's far too early to assume assume the "swelling" is a net harm or that preventing it is good in the long run. Perhaps it serves an important protective or regulatory purpose which we haven't yet identified, because we still know so little about sleep and consciousness. An analogy: There are lots of systems in your body that try to prevent and deter you from casually walking on a damaged leg, and we can override some of them with various external drugs, but that doesn't necessarily mean it's a good idea.
    - code51 2y ago
      So it very well could be that thinking on a worn neuron, trying to do memory access on it, might damage it even more (leg analogy)? It could be possible that the "swelling" could be redirecting brain to use other paths but with caffeine you're utilizing a worn-out neuron. Maybe with chronic deprivation + caffeine habit, you're weakening your cognitive function - repeatedly using a misfiring neuron. At least, with no caffeine, you'd feel your memory is hazy and hard to recall, go to sleep.
      - Terr_ 2y ago
        IANANeuroscientist, but my idle-thought was that a lack of sleep could cause a buildup of waste byproducts, and structural adaptations might either reduce the effect of the buildup or else make its removal marginally easier.

redoubt 2y ago

Medical engineer here; I would suggest anyone whoms interest was caught by the title to read the Discussion, not Abstract. The authors have made good use of the section to broaden their conclusions, answering some of the questions I've observed in this thread. For anyone starting to second-guess their relationship to sleep and caffeine; do note that this is a small-sample study and that more research is needed before any conclusions can be drawn with regards to the population at large. EDIT: I'm not a medical professional (i.e a Doctor), I'm simply an engineer with domain knowledge in medicine. I am accustomed to reading studies like this. If anyone needs help interpreting the study, I'm happy to assist.

iosguyryan 2y ago
To pile on: it’s in Scientific Reports. Not high impact, not highest quality. It’s a 9 day in lab study on mystery taste lab brew coffee (whose brewing was deemed so insignificant to a coffee study that its brew recipe was excluded from the methods section). These sort of setups are useful from a “help me isolate some test cases” point of view, but is obviously as much a perturbation in participants natural lives that it might even outweigh the impact of drinking coffee. Further, it draws conclusions from an acute 5 day caffeine exposure, whereas in real life these participants relationships and adaptations to caffeine are built over a long period of time. The power of the study is small and not scoped for conclusions, but rather pointing to an area of interest for further funding.
bovermyer 2y ago
Thank you for this. I am not anywhere near to a medical professional and can't interpret these results correctly, I'm sure. It's good to have an experienced perspective.
- redoubt 2y ago
  I'm happy you found it helpful, medical studies don't pop up all too frequently here at HN so I try to assist when confusion arises.
deleted 2y ago
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bovermyer 2y ago

The important sentence from the abstract: > In conclusion, our data suggest an adaptive GM upregulation after 5-day CSR, while concomitant use of caffeine instead leads to a GM reduction. I'm not sure what to take away from that. It sounds bad, though.

vouaobrasil 2y ago

I like caffeine. It's fun to drink a cup of tea or coffee once in a while and feel an extra surge of productivity. What I don't like is that it has encouraged the grind of people working far longer and harder than they should for no reason except economic gain which is fundamnetally unsustainable. When people feel tired, they should take a break, and not develop a habit of drinking caffeine every day to keeep going. It's an unhealthy society and reinforces the message that economic gain is important above all else.

velcrovan 2y ago
I think people should be able to do what they want with their time. I don’t think people should have to sell their labor for a wage in order to live. I wonder what happens to your opinions about caffeine in a society where owners have little to no leverage over workers, or where the workers are generally also the owners.
- sershe 2y ago
  > I wonder what happens to your opinions about caffeine Something like this: https://en.wikipedia.org/wiki/East_German_coffee_crisis https://en.wikipedia.org/wiki/East_German_coffee_crisis
- mhb 2y ago
  What kind of tea do they serve in the gulag?
  - velcrovan 2y ago
    I dunno, ask the people who work at Mondragon. https://www.mondragon-corporation.com/en/about-us/ https://www.mondragon-corporation.com/en/about-us/
    - ta988 2y ago
      care to explain?

BossingAround 2y ago

Anyone with anxiety or sleep issues should reexamine their caffeine usage. Maybe those problems do not stem from caffeine, but maybe they do. I don't know many people that do not consume caffeine regularly, at least once a day - in such cases, you cannot know whether your anxiety, sleep problems, general tiredness, bad moods, ... are or are not caused by one's caffeine consumption. Some people swear by drinking a shot of espresso right after dinner, claiming that they can "sleep just fine" (or that it even calms them). It's not whether you can or cannot fall asleep, it's how deep and restorative your sleep is that is important here.

fuzzfactor 2y ago
One of the references in this paper focuses on single sleep deprivation events of a more extreme nature, 48 hours. As I have experienced when regularly (but not often) working a 36-hour day, I wouldn't do it if it wasn't proven to be well within reach, but it's no breeze if you are the least bit tired and not fully prepared beforehand, especially when it comes to nutrition and not having anything toxic in your system. This is completely different than regularly losing sleep every night in a habitual way, which could also be considered somewhat along the lines of everyday exposure to toxic materials, whether toxins enter the body intentionally or not. Don't ask me how I know what it feels like when exposure to different milligrams of different pure industrial chemicals having known toxicity occurs in spite of state-of-the art workplace controls and PPE. I've been working these truly chemical labs all my life. Eventually I felt like I was guinea-pigging caffeine too, and it's old as the hills. The default in many cultures is to be born into a caffeine-addicted society, steeped in excess habitual ritual in a way which encourages never-ending tradition. This is over and above the physical & emotional habit-forming nature of the drug itself. Anyway, culture can be real strong, and I enjoyed being a caffeine addict. It actually takes quite a bit of effort if you want to completely withdraw from its pervasive and widespread exposure, whether commercial influence is involved or not. It's everywhere. With everyday use you build up a tolerance like anything else, and in the long run it really doesn't make a difference whether you lose an hour of sleep every night or get an extra hour, you always feel the same and have the same energy so it must be working, right? Maybe that's supposed to be a red flag. Now when you're actually a pretty good addict, you never overdo it, you're never jittery or considered extreme like a 20-cup-a-day habit which can't be that bad either when so many of them seem to do just fine. But way below any extreme consumption, you can still end up with a fairly late-night dose which actually relaxes you and then you drop off to sleep like you habitually do. Actually without it you might be a little anxious otherwise. It's just your body calling out for what it needs to be normal, due to the current level of tolerance you have built up. Hey wait a minute, wasn't I enjoying this to begin with for it's stimulant effect? Too late, that effect has left the building. This is the part that leads studies like this to less-conclusive results. For me with nothing in the bloodstream almost ever any more (and after all the dust has settled), there's only slightly more energy than being a mainstream addict. I attribute it to the relatively small amount of toxic pressure exerted by the less-than-gram quantities of caffeine I was metabolizing. Yes, I have more energy without it in my system but it's not a miracle and I'm sure many people would not think it's worth it. It's not that toxic, believe me so many things are much worse. But when I need to go another 12 hours, one cup of coffee will do it. Never could be a consideration back when I had a tolerance, stronger stimulants wouldn't even help. Real sleep is the only answer then, you just can't push to the max whenever you really want when you're already strung out. One of the things that makes the 48-hour study more conclusive about usefulness best practices. This was their reference 3: http://scholar.google.com/scholar_lookup?&title=Randomized%2C%20double-blind%2C%20placebo-controlled%2C%20crossover%20study%20of%20the%20effects%20of%20repeated-dose%20caffeine%20on%20neurobehavioral%20performance%20during%2048%20h%20of%20total%20sleep%20deprivation&journal=Psychopharmacology&doi=10.1007%2Fs00213-018-5140-0&volume=236&issue=4&pages=1313-1322&publication_year=2019&author=Hansen%2CDA&author=Ramakrishnan%2CS&author=Satterfield%2CBC&author=Wesensten%2CNJ&author=Layton%2CME&author=Reifman%2CJ http://scholar.google.com/scholar_lookup?&title=Randomized%2...

janpmz 2y ago

Recently I've learned that half of the people are slow caffein metabolizers. The caffein stays longer in their system and it might negatively affect their sleep. Considering how many people drink coffee, I think a lot of people are affected by this.

xen2xen1 2y ago
Found that out the hard way twenty years ago. The stated half life is NOT for me what they say.
b800h 2y ago
Yep - raising my hand here. I've completely given up caffeine (including decaf, which isn't totally) because after I got a Fitbit, I realised that my morning coffee spiked my heart-rate to 120, and kept it thereabouts, slowly dropping to normal overnight, after which I'd start again. A genome sequence shows I'm a slow metaboliser (I expect more will show up with more research). I feel terrific now.
- zemvpferreira 2y ago
  Slow metaboliser here. Also possibly more prone to caffeine addiction than most, according to said genome sequencing interpretation. I need to cap at 2 espressos per day before noon at most, or I start suffering side effects like poor sleep quality. People really need to reframe their coffee consumption from food to drug and understand their own usage and effects of said drug.
  - b800h 2y ago
    Please try quitting entirely. My cold turkey took a week and a half and involved intense muscle pain (going from drinking a coffee and a tea each day). I believe the caffeine was building up in my system, although I could be wrong. I strongly recommend Barleycup as an alternative morning cuppa.
    - zemvpferreira 2y ago

sir-dingleberry 2y ago

[flagged]

lemonlime0x3C33 2y ago

An interesting article to read, would love to see a larger samples size at some point. I am also going to continue drinking my mid-day espresso, morning coffee, and afternoon pick me up caffeine drink...

sir-dingleberry 2y ago

[flagged]

ilaksh 2y ago

I love my caffeine. But caffeine is an addictive, highly profitable substance. So advertising it and trying to promote it as somehow having real health benefits is widespread. I would not be surprised if routine consumption of caffeine was at least mildly detrimental to health. I think some drugs have managed to gain a special place in our society . Advertising and lobbying warps our perception of these drugs. I even saw a comment in this thread suggesting that if caffeine has a prolonged affect on you, then you have some unique genetics and it's essentially your problem, not the drug. Similar to the narrative about alcohol. It's interesting to compare that attitude to the way illegal drugs that can't advertise or lobby are viewed.

2OEH8eoCRo0 2y ago
It's interesting that coffee (black) is essentially perfect (mostly pros, few or no cons) yet there is a small crowd bent on demonizing it.
seoulmetro 2y ago
>Advertising and lobbying warps our perception of these drugs. More like, our own preference and enjoyment of the drugs compared to their detriments constructs our perception of these drugs. Coffee, alcohol, pain killers, etc. These are all drugs that give the user enjoyment with very little down sides. This means that society has reserved a place for them.
mensetmanusman 2y ago
Alcohol reduces functions, caffeine clearly enhances functions. If caffeine was involved in nearly all violent crime like alcohol is, we would think differently of it.
- m463 2y ago
  I think it is a matter of perception. For example, lots of DUI type accidents are blamed on alcohol, but it might actually be sleep deprivation that is the most fundamental cause of the accident. In a similar way, I wonder if similar sleep-related accidents or incidents could more properly have caffeine as a root cause (after it has worn off)

hereme888 2y ago

Caffeine, up to a certain daily dose, is associated with long-term cognitive benefits and a reduced risk of dementia. This study hints that it specifically doesn't benefit gray matter volume during periods of sleep restriction, at least in the short term. I wonder if substances like Ashwagandha extract or Magnesium L-threonate could mitigate gray matter loss during short term sleep restriction among caffeine drinkers.

zemvpferreira 2y ago
It seems more straightforward to simply curb caffeine consumption during periods where you're sleeping poorly. Most people (myself included in the past) would drink more coffee when they sleep less. Grey matter aside, I think this is a very poor strategy. It will make next night's sleep even less effective. Better to drink less coffee, have a shitty day/week, and sleep more restoratively as soon as you can. Don't get in a doom loop voluntarily. Have caffeine only when you're feeling well rested.
azinman2 2y ago
Ashwagandha extract Can only be safely taken up to 3 months. It’s not a long term benefit. Magnesium affects your heart’s signaling, which can be problematic if too much. I’m curious why you asked about Ashwagandha ahd magnesium? They seem to be THE supplements du jour, which is a pretty weird concept. There is a lot of grift going on, and little recognition of the potential negative health impacts of both.
- hereme888 2y ago
  I asked specifically about Magnesium L-threonate due to its ability to increase synaptic connectivity (yet to be conclusively reported in humans) and hence gray matter, and Ashwagandha due to its neuroprotective, neurotransmitter-preserving, and cortisol-lowering effects. I take magnesium daily, including the regular dose of Magnesium L-threonate, and my last CMP showed serum levels within range. Maybe super large medical doses beyond even those used for eclampsia would affect heart conduction, or those who take way more than what supplement bottles recommend. I'm not sure what studies have conclusively shown Ashwagandha to be safe only up to 3 months. I get most of my herbal data from Examine.com (PhD academics that analyze data), where they say: "Some case reports have suggested adverse effects such as rash or thyroid dysregulation may occur with ashwagandha use, but the same has not yet been observed by safety studies with larger samples.[38][39][35] Several case reports have also raised concerns regarding the rare occurrence of liver toxicity with ashwagandha use, but similarly, toxicity has not been observed in clinical safety trials. In the reports, liver toxicity was usually reported within 2–12 weeks of ashwagandha use, and liver function returned to normal in all but one case following medical support and ashwagandha discontinuation.[40][41][42][43][44][45] An in vitro study suggested that withanone (one type of withanolide in ashwagandha), may have toxic effects in the context of low levels of the cellular antioxidant glutathione (GSH), which is involved in drug detoxification.[46] However, this research is far from conclusive and the mechanisms underlying this possible adverse effect are unclear."

marcodiego 2y ago

Rule: if you drink (coffee) dot not stay awake.

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iamleppert 2y ago

I've sad it before, and I'll say it again: the human body is not meant to ingest any other liquid than pure, filtered water.

thebruce87m 2y ago
Maybe you should stop saying it? When we are born we 1) don’t have a filter installed and 2) drink milk.
whamlastxmas 2y ago
Breast milk and the million sources of liquid in the foods we eat disagrees

andro_dev 2y ago

Caffeine does nothing for me at all, I do not get a kick when I drink coffee. It does not affect my sleep, it does not give me a boost at all. So I am a bit of jealous of those who can utilize caffeine for mental boost, I just drink it for the taste.

maipen 2y ago
I used to say the same thing until I tried different types of coffee and different amounts. The average expresso doesn't do much. Also if you are already feeling well, it's unlikely you will feel a big difference unless you consume a high dosage of caffeine, which can also cause you some anxiety. Caffeine is great when we are feeling low energy or sleepy.
- thebruce87m 2y ago
  What specifically do you recommend trying? I don’t seem to get any physical symptoms after a coffee but my wife is the complete opposite.
- andro_dev 2y ago
  Thanks I will try higher dosage.

taeric 2y ago

I am growingly convinced that coffee/caffeine hit people in very different ways. https://www.23andme.com/topics/wellness/caffeine-consumption/ https://www.23andme.com/topics/wellness/caffeine-consumption... has a few fun citations to look through on this, but discussions of how varied we are with how it impacts us is ridiculously invisible in most discussions of it. Sleep is similar. We speak of "night owls" and such, but most discussion around the varied needs of sleep are age targeted. With most discussion on how we should let kids sleep longer.

claytongulick 2y ago
I'm one of those. I have this super weird thing where I'm hyper-sensitive to caffeine, and its effects will hit me sometimes 6+ hours later. If I have a cup of coffee in the late morning, it will keep me up most of the night, and a single cup of coffee will make me manic-ish. People have (doctors included) told me that what I was experiencing was impossible, that caffeine in metabolized in a certain way and completely out of your system quickly. Turns out, that's true with most people, unless you have a variant in the CYP1A2 gene, which can cause the effects I experience.

lanstin 2y ago

On a cultural note regarding the threads, the moralistic make do with what god gives you side and the yay drink coffee and do stuff and be happy side have been around a long time. A little Bach Cantata about a grumpy old dad and his coffee drinking daughter: https://youtu.be/nifUBDgPhl4?feature=shared https://youtu.be/nifUBDgPhl4?feature=shared

sandworm101 2y ago

>> Each participant underwent a 9-day laboratory visit consisting of one adaptation day, 2 baseline days (BL), 5-day sleep restriction (5 h time-in-bed), and a recovery day (REC) after an 8-h sleep opportunity. Was this a vacation? Was this study done at a resort? During push times I aspire to 5-hour sleep times. Talk to anyone in any branch of the military. During any sort of active operation, 5-hours in bed is total luxury. Or fishers. Or cops. Or food service workers. Or doctors.

EZ-E 2y ago

Side topic, but dropping coffee was the best thing I ever did. I used to drink only one cup a day, rarely two, for many years - but turns out when I stopped (for reasons unrelated) my anxiety unexpectedly 80% went away after a week or so without any other changes in my lifestyle. It was a big difference and I feel now very different than what I used to. I wake up much better rested too (much easier to get out of bed). Too bad, I really loved the taste but it's not worth it for me. I encourage anyone to give it a try a few weeks and see how they feel. You may not realize what you thought is your baseline is in fact caused by caffeine sensitivity. I heard of some people being sensitive to caffeine but I never thought it would affect me, after all I did not have that bad of a reaction but it really built up and I had gotten used to it.

obruchez 2y ago
I've been suffering of anxiety for decades. Nothing really serious. I stopped caffeine for one month in 2022, cold turkey. No coffee. No tea. No chocolate. I stopped alcohol as well (I don't drink much, so it wasn't really hard). I track a lot of things daily and during this abstinence period, my anxiety didn't decrease. On the contrary, it (very slightly) increased. This, of course, was not a controlled/blinded experiment, the duration was rather short (1 month), N=1, and I actually did two experiments at the same time (caffeine + alcohol), which is not optimal. In summary, my conclusion is that I prefer drinking coffee (max 2-3 small cups daily, in the morning) than not. Still, I'd like to try the experiment again in the future and stop caffeine for a longer period this time (3 months?). Edit: I'm a slow metabolizer (rs762551 = AC).
curmudgeon22 2y ago
I've had a very similar experience. If i drink coffee daily, it bumps my anxiety significantly after a few days or a week. If i rarely have it, it's usually fine. But if I let myself have it, it's too easy to trend towards daily again. I drank coffee for years and don't think it had an impact, but at some point, I noticed it and the impact was very real when not drinking it.
amirbehzad 2y ago
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amirbehzad 2y ago

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broguinn 2y ago

I haven't seen this mentioned in the comments yet, so I'll mention it here. For the last year, I've seen health pundits (Huberman, etc.) recommend delaying caffeine intake for two hours after waking, for the purpose of allowing adenosine to clear from the brain first. Ever since I've adopted this strategy, I find myself avoiding a mid-morning crash, and generally feeling more alert in the mornings. I wonder if the deleterious impact on grey matter could be mitigated in part by delaying consumption until fully awake.

ninininino 2y ago

Are any of these results applicable to a non sleep-restricted state? The study was on 5 days of 5-hr sleep only. How does caffeine affect 8-hrs sleep?