4 ms·

(Former neuroscientist here.) This is true of caffeine, for example, which is an adenosine analog (e.g. it has a similar shape and fits into the same receptors)

by qiqing 11y ago

(Former neuroscientist here.) This is true of caffeine, for example, which is an adenosine analog (e.g. it has a similar shape and fits into the same receptors). Adenosine is a signal to a cell that it's running low in energy. Caffeine competitively binds to the spots on receptors where adenosine goes, effectively preventing the cell from communicating its low energy state. Now here's the kicker. When your body builds 'tolerance' for caffeine, what this usually means* is the post-synaptic cell adjusts how much adenosine it's pumping out so that the "I'm tired" signal can cut through the caffeine. And when you go through caffeine withdrawal, it takes a while for those levels to re-adjust to normal. * in the brain. Caffeine also has effects on your digestive tract, blood pressure, and some other non-brain parts. :) Edit: corrected cAMP -> adenosine (simple recall error from a lecture that was 9 years ago). The gist of the reply remains the same.

allencoin 11y ago
Knowing what you do of neuroscience and caffeine, do you personally consume caffeine? Do you think it is a "Bad Thing" to drink coffee?
- qiqing 11y ago
  I think it's useful to think of it not as a "bad thing" but as a very high-interest loan from your future self. In moments of weakness and pushing a deadline, I have sometimes rationalize the trade-off of future time/health to present time, and sometimes, that sticks me with tolerance that it takes time to wean off. I have made a conscious effort to quit caffeine dozens of times in my life, and the most recent time it has stuck, and I plan to stick with it. The thing is, when I gain "time" with caffeine, it's not necessarily time with high-quality cognition or productivity compared to my well-rested self, and it's easy to forget to take that into account when you're making trade-off decisions when tired. You still perform like a tired person, you're just not subjectively feeling the tiredness. FWIW, drinking decaf gives you the health benefits of coffee with 5% (kinda negligible) amounts of caffeine.
  - dj-wonk 11y ago
    Which kind(s) of decaf do you like? They are made by different processes, and I wonder which ones are 'more natural' or healthier.
    - qiqing 11y ago
      Personally, I enjoy the flavor of Swiss water decaf more than others (and by reasoning of the "Dorito effect," that flavor may have something nontrivial to do with the nutrients left in it; it also happens to not use additional solvents). That said, a lot of the risky solvents used in the usual methods of making decaf are no longer commercially used these days, so I don't think there's a serious health risk in drinking any ol' decaf you want.
  - ElComradio 11y ago
    I had heard that alcoholics who drink coffee have a markedly decreased chance of developing cirrhosis, something like a 60% reduction. But only for regular caffeinated coffee- not tea, not decaf coffee. Do you have any insight into why or is this not true?
    - qiqing 11y ago
      Huh, I hadn't seen that until just now, but I looked up this paper (http://www.ncbi.nlm.nih.gov/pubmed/11557177 http://www.ncbi.nlm.nih.gov/pubmed/11557177) and a more recent one that cited that one: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110174/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110174/ Notes for below: * CHB/CHC -> chronic hepatitis B/C * NAFLD -> Non-alcoholic fatty liver disease When discussing possible mechanisms for their findings: "We postulate that the observation of the benefit of coffee on the progression of liver disease may be due to its effects on the oxidative stress/lipotoxicity pathway, which underlie the pathogenesis of cirrhosis related to alcohol, NAFLD and possibly, in part, CHC. However, since oxidative stress is not the predominant mechanism of injury seen in CHB, coffee has no beneficial effect. Polyphenols and melanoidins, which are major components of coffee, have been shown to mediate multiple protective mechanisms in a rat model of steatohepatitis, ranging from increased fatty acid β oxidation, mitigating oxidative stress and curtailing liver inflammation (47). The other components of coffee, cafestol and kahwoel, can induce phase II detoxifying enzymes, including sulfotransferase, UDP-glucuronosyl transferase, glutathione transferase and peroxidase, and thus contribute to the anti-oxidant properties of coffee (14, 48). In addition, chemicals in coffee such as polyphenols and the diterpenes have been shown to down-regulate proinflammatory, fibrogenic cytokines such as transforming growth factor beta (TGF-β) and its downstream modulator, connective tissue growth factor (CTGF), collagen and stellate cell activation (13–16). Epidemiologic studies on caffeine have been inconsistent in demonstrating a protective effect in liver disease since other caffeine-containing beverages such as tea have not shown to be protective (19–21). Similarly, in our study, the inverse association with caffeine became null after adjustment for coffee, suggesting that ingredients of coffee other than caffeine appear to be responsible for this beverage’s effect on risk reduction. Furthermore, other caffeine-containing beverages like green tea and black tea had no significant effects with cirrhosis mortality in this study."
lvs 11y ago
This is incorrect information. (... Like so many biology/chemistry comments I see on HN.) Caffeine is more like an adenine analog, not a cAMP (3'-5' cyclic adenosine monophosphate) analog. It binds adenosine receptors, not primarily cAMP receptors. It has indirect effects on cAMP, but I am not aware of direct ones. Also, your description of cAMP signaling sounds confused, since cAMP is an intracellular second messenger. I am not aware of an extracellular retrograde signaling process for this molecule. Sorry, and your implication that cAMP is a byproduct of ATP consumption is totally wrong. cAMP is synthesized directly from ATP, a reaction catalyzed by the regulated enzyme adenylate cyclase.
- qiqing 11y ago
  Thank you for the correction. I mis-remembered a minor detail from a lecture that was 9 years ago, and have find/replaced cAMP -> adenosine in the above post. The gist of the post, though, remains the same. That is, caffeine competitively inhibits receptors that gate ion channels, and the mechanism of tolerance is an increase in the concentration of the thing that it competitively binds. (My thesis was on auditory cognition and I haven't touched ion channel biophysics in that long. I have a long-ago memory that adenosine (now corrected) operated as a retrograde transmitter, though since I'm probably not going to spend my afternoon looking for the citations, I'll delete as well for now. Not because I believe it's wrong, just that I can't immediately back it up.) Are you still doing research yourself or have you left for startup land like most of HN?
  - lvs 11y ago
    Thanks for making your corrections as well. Yes, I am in research, and I mostly come here for what's new in Python, learning algorithms, and data analysis. As an aside, it's tough to wade through the "startup land" and personal health advice and keep a straight face in all honesty, but there are few other places that aggregate the things I'm interested in on the computing side of things. An "HN" with users that specialize in bioscience would be very interesting, but I don't know of one with any level of seriousness/activity.
    - 11y ago

by qiqing 11y ago

allencoin 11y ago

Knowing what you do of neuroscience and caffeine, do you personally consume caffeine? Do you think it is a "Bad Thing" to drink coffee?

qiqing 11y ago
I think it's useful to think of it not as a "bad thing" but as a very high-interest loan from your future self. In moments of weakness and pushing a deadline, I have sometimes rationalize the trade-off of future time/health to present time, and sometimes, that sticks me with tolerance that it takes time to wean off. I have made a conscious effort to quit caffeine dozens of times in my life, and the most recent time it has stuck, and I plan to stick with it. The thing is, when I gain "time" with caffeine, it's not necessarily time with high-quality cognition or productivity compared to my well-rested self, and it's easy to forget to take that into account when you're making trade-off decisions when tired. You still perform like a tired person, you're just not subjectively feeling the tiredness. FWIW, drinking decaf gives you the health benefits of coffee with 5% (kinda negligible) amounts of caffeine.
- dj-wonk 11y ago
  Which kind(s) of decaf do you like? They are made by different processes, and I wonder which ones are 'more natural' or healthier.
  - qiqing 11y ago
    Personally, I enjoy the flavor of Swiss water decaf more than others (and by reasoning of the "Dorito effect," that flavor may have something nontrivial to do with the nutrients left in it; it also happens to not use additional solvents). That said, a lot of the risky solvents used in the usual methods of making decaf are no longer commercially used these days, so I don't think there's a serious health risk in drinking any ol' decaf you want.
- ElComradio 11y ago
  I had heard that alcoholics who drink coffee have a markedly decreased chance of developing cirrhosis, something like a 60% reduction. But only for regular caffeinated coffee- not tea, not decaf coffee. Do you have any insight into why or is this not true?
  - qiqing 11y ago
    Huh, I hadn't seen that until just now, but I looked up this paper (http://www.ncbi.nlm.nih.gov/pubmed/11557177 http://www.ncbi.nlm.nih.gov/pubmed/11557177) and a more recent one that cited that one: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110174/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110174/ Notes for below: * CHB/CHC -> chronic hepatitis B/C * NAFLD -> Non-alcoholic fatty liver disease When discussing possible mechanisms for their findings: "We postulate that the observation of the benefit of coffee on the progression of liver disease may be due to its effects on the oxidative stress/lipotoxicity pathway, which underlie the pathogenesis of cirrhosis related to alcohol, NAFLD and possibly, in part, CHC. However, since oxidative stress is not the predominant mechanism of injury seen in CHB, coffee has no beneficial effect. Polyphenols and melanoidins, which are major components of coffee, have been shown to mediate multiple protective mechanisms in a rat model of steatohepatitis, ranging from increased fatty acid β oxidation, mitigating oxidative stress and curtailing liver inflammation (47). The other components of coffee, cafestol and kahwoel, can induce phase II detoxifying enzymes, including sulfotransferase, UDP-glucuronosyl transferase, glutathione transferase and peroxidase, and thus contribute to the anti-oxidant properties of coffee (14, 48). In addition, chemicals in coffee such as polyphenols and the diterpenes have been shown to down-regulate proinflammatory, fibrogenic cytokines such as transforming growth factor beta (TGF-β) and its downstream modulator, connective tissue growth factor (CTGF), collagen and stellate cell activation (13–16). Epidemiologic studies on caffeine have been inconsistent in demonstrating a protective effect in liver disease since other caffeine-containing beverages such as tea have not shown to be protective (19–21). Similarly, in our study, the inverse association with caffeine became null after adjustment for coffee, suggesting that ingredients of coffee other than caffeine appear to be responsible for this beverage’s effect on risk reduction. Furthermore, other caffeine-containing beverages like green tea and black tea had no significant effects with cirrhosis mortality in this study."

lvs 11y ago

This is incorrect information. (... Like so many biology/chemistry comments I see on HN.) Caffeine is more like an adenine analog, not a cAMP (3'-5' cyclic adenosine monophosphate) analog. It binds adenosine receptors, not primarily cAMP receptors. It has indirect effects on cAMP, but I am not aware of direct ones. Also, your description of cAMP signaling sounds confused, since cAMP is an intracellular second messenger. I am not aware of an extracellular retrograde signaling process for this molecule. Sorry, and your implication that cAMP is a byproduct of ATP consumption is totally wrong. cAMP is synthesized directly from ATP, a reaction catalyzed by the regulated enzyme adenylate cyclase.

qiqing 11y ago
Thank you for the correction. I mis-remembered a minor detail from a lecture that was 9 years ago, and have find/replaced cAMP -> adenosine in the above post. The gist of the post, though, remains the same. That is, caffeine competitively inhibits receptors that gate ion channels, and the mechanism of tolerance is an increase in the concentration of the thing that it competitively binds. (My thesis was on auditory cognition and I haven't touched ion channel biophysics in that long. I have a long-ago memory that adenosine (now corrected) operated as a retrograde transmitter, though since I'm probably not going to spend my afternoon looking for the citations, I'll delete as well for now. Not because I believe it's wrong, just that I can't immediately back it up.) Are you still doing research yourself or have you left for startup land like most of HN?
- lvs 11y ago
  Thanks for making your corrections as well. Yes, I am in research, and I mostly come here for what's new in Python, learning algorithms, and data analysis. As an aside, it's tough to wade through the "startup land" and personal health advice and keep a straight face in all honesty, but there are few other places that aggregate the things I'm interested in on the computing side of things. An "HN" with users that specialize in bioscience would be very interesting, but I don't know of one with any level of seriousness/activity.
  - 11y ago