Thursday, September 29, 2011

Happy Happy Coffee!

I'm really falling behind my stack of papers.  Fortunately, life is good and busy, and there are always new, catchy songs to listen to:

The Temper Trap:  Fader

That song really puts a spring in my step.  Rather like a strong cup of coffee.  Full disclosure - more of a tea person, but I've been known to drink a cup of joe every now and again.  Maybe I ought to drink a bit more… the evidence is mixed, frankly.  And certainly I can't tell you how many times I've had patients complain of insomnia, only to find out they are drinking 6 large iced coffees a day, or 12 Mountain Dews (no matter how much I exercise, I don't seem to be able to take this weight off, doctor…).

But what does the research say about, say, depression and coffee?  A brand spanking new piece of epidemiology from the Nurses' Health Study was published in the Archives of Internal Medicine this month - Coffee, Caffeine, and Risk of Depression Among Women.

Some facts from the article - 80% of the caffeine in the world is consumed as coffee.  Interesting.  Prospective studies of men and caffeine use showed a strong inverse association between coffee drinking and depression, with no association for tea or cola.  Three cohort studies showed an inverse relationship between coffee consumption and suicide (though in a Finish study, there was a J-shaped curve with both very high (>7 cups of coffee daily) and low consumption of coffee seemingly less protective than moderate amounts.)

So, in the Nurses' Health Study (following 121,700 American female nurses starting in 1976), women filled out questionnaires every two years.  97,000 filled out questionnaires in 1996, 98, or 2000, and those with no history of depression at that time (50,739 women) (those with unknown history were excluded) were followed over the next decade.

Regular coffee drinkers in this cohort were more likely to be smokers, drinkers, and not go to church!  They also tended to have lower rates of diabetes and obesity.  Average consumption for the whole group was about 1&1/2 cups of coffee a day.

Among the 51,000 women, about 2600 developed clinical depression in the 10 year period.  There was a dose dependent, inverse relationship between the amount of coffee consumed and the risk of developing depression over the years.  When covariates (such as age, health, smoking, divorces, etc. etc.) were all adjusted for, the inverse relationship became even stronger!  No associations were found between tea consumption, chocolate consumption, decaf coffee, or soda consumption and depression.

So what's up?  Is coffee an antidepressant?

I Know What I Am: Band of Skulls

Well, maybe.  This is no randomized controlled trial, so causation cannot be determined, but caffeine (1,3,7-trimethylxanthine) antagonizes the adenosine A2A receptor.  This is thought to have pro-dopamine effects.  By taking out adenosine, we might also be affecting the transmission of norepinephrine and serotonin, both known targets of antidepressant medicines.

Since coffee is known to cause insomnia and anxiety, both features of depression, a weakness of the study is that women prone to insomnia and anxiety might limit their intake of coffee, thus biasing the results so that women who can tolerate a truckload of coffee also happen to be the ones less prone to depression.

But… all told, it seems that this study is another notch in coffee's bedpost.  Though less than 8 cups a day seems prudent.  And I really can't recommend Mountain Dew :)


  1. Speaking personally, I find caffeine to be important for my mental state and I dose myself as I do any of my supplements, I treat it as a drug. I weigh ~115-120lbs and I try to keep an intake circa 300-400mgs daily. I do best with caffeine intake mid day (the largest bolus) and this is when I crave it. I cut myself off several hrs before bed, or I may only have a small cup of soda or something trivial like that (note, my tolerance is so high, a cup of soda to me is like a normal person drinking a cup of tea).

    One time a vendor accidentally gave me decaf; I had no access to caffeine for nearly 24 hrs. Toward the end of the night I literally could not think, as if I was given a first dose of antipsychotic medication. I had to stop and get caffeine when I nearly passed out (probably low sugar was complicating things - I imagine my sugar was so low preicsely because of caffeine w/d).
    This instantly reversed itself upon drinking caffeine.

    When I had surgery and was fasting, in spite of being drugged up and barely awake one of my first requests was caffeine, lol. I still remember that. Forget pain meds, fix me a cup of coffee stat.

    In the past when going through depression, coffee is the only thing I can really motivate myself to think about or want, its the only thing that can slightly make me feel a little better. Literally my whole life revolves around coffee, getting the energy to get it or make it. I am rather certain my depression would be considerably worse if I did not use stimulants in the form of coffee, as most of my depressive symptoms are the opposite of what it does. And I am thankful that anything stronger than coffee is regulated and illegal.

  2. I think the link between depression and caffeine intake is mostly correlational;

    It's known that animals (and humans) with higher dopamine sensitivity will more compulsively administer stimulants, such as cocaine as well as presumably caffeine. Food restricted animals, as well as humans, and patients status post bypass surgery, are all known to develop dopamine dependent issues (compulsive gambling, sex addiction, drug addiction) and this is precisely because their brain is hypersensitive to dopamine after starving.

    It stands to reason, then, that a person with uber dopamine sensitivity in the brain is less likely to get depressed, and also more likely
    to be like RAAAR CAWFEEE!!!

    Again speaking personally when I was a big fattie eating lots of carbz and very depressed, I had zero response to caffeine. It did absolutely nothing for me, and I suspect that is because back then my dopamine sensitivity was horrible secondary to high glucose intake and obesity which is known to cause functional dopamine receptor downregulation (rapidly reversed upon glucose restriction, and I do think this is part of the reason I find a low carb diet so absolutely essential for controlling my depression as most of my depression seems rather dopaminergic).

  3. I am on my 23rd day coffee-free. I did this because I have read that coffee can cause a cross reaction with gluten:

    what do you think about it? Does it make sense to avoid gluten and not coffee? What about coffee's impact on hormonal balance (estrogen vs progesterone)? Doesn't it suppress testosterone and therefore cause sub-clinical depression?

  4. Could it be how coffee is consumed? It is a highly social drink. Perhaps those who consume coffee, cigarettes, alcohol, etc, are protected from depression to a degree by the social support structures that go with their coffee fix?

  5. i don't leave the house with fewer than 3 cups. strong coffee too. not that weak diner shit. this is Portland for cryin out loud. i usually have 4 or 5 more at work, but never after 2. i sleep like a stone. since going paleo and confirming my celiac haven't had a day of gerd either. dropping gluten seems to have fixed most of my mental dysfunction and short tempered depression type stuff.
    they drink shit loads in sweden and i hear tell they are the happiest people on earth.

  6. I'm sticking with green tea:

    I do very badly on coffee when I'm stressed out, but I like it when I am relaxed and have nothing to worry about. Go figure.

  7. This is very interesting since I was thinking only just now about this, in the context of my daily battle with myself as to whether to have any caffeine in the morning.

    In my experience I certainly feel a lot better over the medium term when I completely abstain from caffeine. Even very small amounts make a substantial difference and I tend to limit myself to about 25mg per day as a kind of background dose. I seem to be very caffeine sensitive, both in the sense of experiencing negative effects very quickly but also noticing and feeling the effects of reduced amounts very sensitively. Withdrawal for me is absolutely hellish, hence why I tend to consume around 25mg daily, rather than cut straight to zero. Hence why I fine-tune my doses so specifically. I tend to feel worse in proportion to how much caffeine I consume, (higher amounts make me feel sick, jittery, washed out and I get ill- like clockwork- if I have to take larger amounts of caffeine to get some work done) obviously there are lots of confounding variables here though.

    The reason why this post is particularly interesting, is because I found that a lot of the negatives of caffeine and some of the positives were actually due to other compounds in the caffeine-beverages- the negatives, I assume, from the tannin in tea, coffee, cocoa. The extra positives are most noticeable from cocoa by a large extent, which is qualitatively different to the effects of caffeine and my preferred stimulant. I've not noticed any particularly significant other effects from coffee/tea, but there may well be some. I'd be fascinated to know how much of this is due to theobromine and how much due to the other chemicals which have been suggested to reduce stress and impact gut flora ( Indeed, given the links between mental state and gut flora, I often wonder if the (positive) effects I get from tannic drinks are due to the tannins combating poor gut flora. As to the negative effects of these tannic drinks. I discovered that a lot of the negative effects I'd ascribed to caffeine- jitteriness, digestive disturbance, sick feeling and so on are actually due to the tannins in the drinks. Hence I don't get them anywhere near as much from energy drinks or caffeine pills and the effects of the tannic drinks are heavily ameliorated by adding dairy protein to them.

    I was also interested by you saying that coffee itself was negatively correlated with depression, because I recall that cocoa (despite the purported anti-depressant effects) is positively correlated with depression ( Of course, who knows which way around causation runs.

  8. Woo - It would be implausible that (on a population level) the high coffee consumers are all successfully self-medicating their depression - that would mean that without the coffee, the people drinking more coffee now would be more depressed than those drinking less coffee… and that would mean that coffee is an incredibly effective, superfly antidepressant, which seems unlikely. Certainly on an individual level almost anything could happen.

    Now the authors of the paper were rather unimaginative in bringing up (solely) the monoamine hypothesis of depression (serotonin, norepinephrine, dopamine). I'm guessing that may be a part of the picture, but also speculate that the high levels of caffeine in coffee have energy efficiency-preserving implications and anti-inflammatory effects. IF the coffee monoamine hypothesis is true, one might expect coffee consumption to be positively correlated with mania in those who have the vulnerability to it. Tough as caffeine can cause insomnia, which also causes mania…via a monoamine mechanism, perhaps!

    Thalin - I don't know. If one had celiac I suppose one could follow gluten-eposure biomarkers if one were worried. Those aren't 100% but might be helpful? Again, one would have some explaining to do for coffee to be a cause of depression and have a strong inverse correlation with it, but stranger things have happened and there are obviously confounders.

    Jamie - in separate studies, alcohol consumption and cigarette smoking all have positive correlations with depression. That is why the inverse correlation between coffee and depression increased when adjusting for confounders statistically - the increased cigarette consumption with coffee accounted for the difference. The social aspects are definitely other confounders - I think they would be harder to quantify and account for statistically.

    Dan - the funny thing about the Finnish study is that the *lowest* group consumed something like 416mg of caffeine a day - that's nearly double the nurse's health study average consumption. And, again, the positive correlation with suicide in the Finnish study happened at greater than 7 cups of coffee a daily - but it was consistent through 8, 9, and 10 cups a day. The Finns and Swedes and Portlandians love their coffee :-)

    Rudolf - I'm a tea drinker. But maybe I should switch up ;-) (seriously, we don't have enough info to make a recommendation here as there are no RCTs, but it is interesting!)

  9. I've eaten baking chocolate in the late afternoon or after dinner before and been unable to sleep for the entire night. The only times I've drunk coffee after dinner I pulled (not voluntarily) all-nighters as well. Sometimes if I have a morning/lunchtime cup, I become really social, and I feel like I can read really fast, while other times I get a bit more manic, and my focus is horrible. I never thought to check whether cream affects this, as sometimes I have a lot (like 1/3 cream, 2/3 coffee); sometimes I drink black.

  10. Two things occur to me: one, when I drink a lot of caffeine relatively quickly, I actually get a very brief euphoric high, suggestive of effects beyond mere alertness. The second, mostly opposing thought: I think it is pretty well established that different genotypes metabolize and react to caffeine differently, and, just as has been proposed for the inverse coffee/Parkinson's correlation, it might be that people that don't react well to caffeine are more prone to depression (as they are to Parkinson's). Dosing them extra coffee would make them jittery in addition to possibly leaving them depressed.
    Fortunately for me, I react well to coffee. Note my avatar.

  11. This is an interesting one. I dropped drinking caffeine a long time ago to try and address insomnia and it worked to some extent. The only caffeine I have comes in 85-90% chocolate, may be 60 g a day. I have recently had more sleep issues and it may be the chocolate I suppose. However, if you read Candace Pert's Molecules of Emotion you'll soon discover that it's much more interconnected than just a + b = c. I do know that drinking coffee totally 'wires' me and promotes mania and sleeplessness, but I'm sure there are other factors too. I'm looking at the broader picture now my paleo eating (no dairy, no grains, minimal added sugars) has given me some mental stability and I see the road to optimum health through a multi-faceted approach and have started investigating some of the ancient medicinal arts too - yesterday was my first acupuncture experience and that was fairly mind blowing; much of what we 'suffer' is to do with all that has been before which is why everyone's response is so individual and why 'treatment' needs to be bespoke.

  12. From what I have read about caffeine I can´t reach a conclusion on the effect of caffeine: does it work on alertness just because you compensate withdrawal or is it active?.

    You should try yerba mate. :)

  13. Why some people are unable to notice any coffee effect at all? If I have it before I go to sleep I will sleep just fine. O.k., my BMI is 27(used to be 31 4 years ago), I could be like the Woo in a fat period of her life, but my naturally thin 18 yo son has the same reaction on a coffee.

  14. i wonder if the "antidepressant" effect is simply because of a comforting daily ritual for the depressed person who can handle coffee.

    but i can't consume it more than two days in a row without my heart starting to pound.

    too bad 'bout dat... love the stuff.


  15. @Jamie

    I like my coffee is like gollum likes his ring. I prefer it alone in a cave where I can whisper over and over again, "my preciooous". Or, alternatively, compulsively read and rant on the interweb, or clean a lot, or work in a stressful fast paced condition.

    Speaking as half a crazy person, caffeine makes the ordinary exciting, it makes it so that when I am quiet I suddenly begin talking and rambling, makes music sound better and more intense, makes ideas more interesting, makes my thoughts more exciting, gives me the energy to move and clean, completely restores my functioning in spite of not sleeping, etc. Basically caffeine is the "on" switch in my brain. I suspect this is so because I am now addicted to it and have no choice in the matter but to drink it just to function mentally, but all the same it is still true. Caffeine, to me, is just as vital if not more vital than food and water. I would seriously prefer to have a day where I was allowed only trivial amounts of food/water, rather than a day totally caffeine free. I would function much better if I was able to keep my caffeine.

    When I am depressed, caffeine is the difference between my level of apathy and misery and lethargy. I would sort of compare it to the way a person in pain after an injury might feel for the 4 hrs after medicine. They don't feel good, they aren't functioning as well as they are when they are injury/pain free, but that little pain pill is the difference between suffering badly vs anticipating and feeling some temporary relief, and improving functioning for a little while, and a little while timed properly is a big deal.

    Yea I find it real easy to believe that coffee/caffeine drinkers have less depression, but again, I think it is mostly correlation as being able to respond to caffeine is a sign of having in tact dopamine function in the brain, and it is the normal dopamine function in the brain which truly protects against depression (using caffeine is just a passive symptoma of having functional / sensitive dopamine receptors).

  16. @Galina as David said perhaps you are (unfortunate) in that you do not have the genetics to metabolize and respond to caffeine in a typical fashion? Sort of how I never experience any high from sugar but many people report how much pleasure and excitement and high they feel after eating sucrose food, I have never really felt this "high" and the closest I have experienced is maybe, sometimes, relaxation.

  17. Theres a comment:
    But alas, I can't access it.

  18. Rudolph, I read it. Doesn't add much (usually comments are very interesting, not this one) - just basically says - don't everyone use this study to start drinking 6 cups of coffee a day, it's observational, blah blah blah :-)

  19. @ The Woo
    I wouldn't mind to enjoy something as much as you enjoy your cup of coffee(I believe that a coffee addiction is not a health risk). I also never experienced a sugar high and never manage to develop an addiction to tobacco when I used to smoke for social reasons because my than-boy-friend smocked(it lasted for approximately 3 - 5 years). I am sort of a relaxed kind of individual, drink mostly tea and have my coffee often daily because I like the taste. Caffeine has tendency to make my migraine worse when I have one.
    I like to read your comments on all blogs.

  20. I am having problems to post comments here. Sorry if repeated.

    From what I have read about caffeine I can´t reach a conclusion on the effect of caffeine: does it work on alertness just because you compensate withdrawal or is it active?.

    You should try yerba mate. :)

  21. Hi there. As an Iraqi in Algeria since one year I am still fascinated by Espresso coffee which we don't have in Iraq. i drink two big cups aday. I like your blog alot. Sami, a non-practicing psychiatrist, Bou Saada, Algeria.

  22. I recently read an article in Forbes about Michael Ellsberg who says he overcame bipolar II by modifying his diet ( - no alcohol, sugar or caffeine. I was recently diagnosed with bipolar II, and while I needed no convincing regarding the role that high GI carbs and alcohol play in my mood, I was curious about caffeine. If I understand correctly, dopamine can worsen mania - so if caffeine has pro-dopamine effects, could that explain how it could worsen the symptoms of a person with bipolar?

  23. Jenice - yes, a compelling article. And while I think the standard recommendation to avoid coffee in bipolar is due to the importance of good, restorative sleep, the presumed antidepressant and dopaminergic effect of caffeine (which remains speculative) would be another (perhaps even more compelling) reason for folks with bipolar to avoid high doses of caffeine like coffee and energy drinks.


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