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jsalvatier comments on Living Forever is Hard, or, The Gompertz Curve - Less Wrong

46 Post author: gwern 17 May 2011 09:08PM

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Comment author: jsalvatier 18 May 2011 03:31:57PM 3 points [-]

You've convinced me to look into this. Do you have a link to the metastudy? Have you considered a top level post about this?

Comment author: satt 19 May 2011 04:58:24AM 8 points [-]

I got curious too and found an online copy. Reference: Rothwell et al. (2011), "Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials", The Lancet, vol. 377, pp. 31-41.

Comment author: [deleted] 19 May 2011 06:32:57AM 1 point [-]

Fascinating - I learned several things from the full text. Have an upvote!

Comment author: TimFreeman 20 May 2011 10:35:30PM *  0 points [-]

Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials

Based just on the title, they seem to be looking at the wrong thing. You want to know the effect of daily aspirin on long-term risk of death, not on long-term risk of death from cancer. Your life isn't improved much if you trade death from cancer for death from (say) depression and suicide. (I have no reason to expect such a trade.)

I read the abstract too, and my concern was not changed. I have not read the whole paper.

Nevertheless, if that's the best available information, that's worth knowing. Thanks for posting it. Have an upvote.

Comment author: satt 21 May 2011 05:17:36AM 3 points [-]

I haven't read the whole paper, but I also wanted to see what aspirin's effect on all causes of death was. (I wondered whether the higher risk of bleeding would offset the lower risk of cancer; it didn't.) The magic keywords to Ctrl-F for are "all-cause".

p. 34:

The reduction in cancer deaths on aspirin during the trials resulted in lowered in-trial all-cause mortality (10.2% vs 11.1%, OR 0.92, 0.85–1.00, p=0.047, webappendix p 4), even though other deaths were not reduced (0.98, 0.89–1.07, p=0.63).

p. 36:

In patients with scheduled duration of trial treatment of 5 years or longer, all-cause mortality was reduced at 15 years’ follow-up (HR 0·92, 0·86–0·99, p=0·03), due entirely to fewer cancer deaths, but this effect was no longer seen at 20 years (0·96, 0·90–1·02, p=0·37). However, the effect on post-trial deaths was diluted by a transient increase in risk of vascular death in the aspirin groups during the first year after completion of the trials (75 observed vs 46 expected, OR 1·69, 1·08–2·62, p=0·02), presumably due to withdrawal of trial aspirin.

p. 39:

Fourth, we were unable to determine the effect of long-term (eg, 20–30 years) continued aspirin use on cancer death or all-cause mortality because of the finite duration of the trials.

and

Our analyses show that taking aspirin daily for 5–10 years would reduce all-cause mortality (including any fatal bleeds) during that time by about 10% (relative risk reduction). Subsequently, there would be further delayed reductions in risk of cancer death, but no continuing excess risk of bleeding.

The big caveat I have in light of this is that the trial patients were in their 40s and older. I would guess the cost-benefit balance tilts the other way for sufficiently young people because younger people have a lower risk of cancer or CVD.

Comment author: [deleted] 19 May 2011 05:17:28AM 2 points [-]

You've convinced me to look into this.

Cool. I also convinced LukeStebbing, my best friend, to begin taking low-dose aspirin. He researched (i.e. looked up on the Internet) its interaction with moderate alcohol consumption, which I currently don't consume (although if he's right about its health benefits, I should - the problem is that there aren't any massive RCTs demonstrating a clear effect). I'm harassing him now to add a comment about what he learned.

Do you have a link to the metastudy?

The NYT linked to its abstract at The Lancet's website. The full text is behind a paywall.

Have you considered a top level post about this?

If post-ifying long comments is kosher, I could do that - but I really have nothing more to add, except one more thing I remembered. Aspirin and its NSAID relatives share similar-but-different mechanisms of action - aspirin is special because it has irreversible effects, see Wikipedia's article for more info. In particular, this means that other NSAIDs can interfere with aspirin (not in a way that's likely to do nasty damage to you - there are plenty of those interactions - but in a way that blunts aspirin's special effects). As a result, while I used to occasionally take ibuprofen for headaches, when I began low-dose aspirin I stopped doing that. Now, when I have a rare headache, I'll take full-strength aspirin.

Comment author: LukeStebbing 19 May 2011 05:52:10AM *  5 points [-]

I didn't actually do much research; I just went through several pages of hits for aspirin alcohol and low-dose aspirin moderate alcohol. I saw consistent enough information to convince me:

  • never to take them at the same time, sample:

    In a paper published in the Journal of the American Medical Association, researchers at the Veterans Administration Medical Center in the Bronx found that taking aspirin one hour before drinking significantly increases the concentration of alcohol in the blood.

  • that the nasty interactions only seemed to happen at 21+ drinks per week, sample:

    There is no proof that mild to moderate alcohol use significantly increases the risk of upper gastrointestinal bleeding in patients taking aspirin, especially if the aspirin is taken only as needed. However, people who consumed at least 3-5 drinks daily and who regularly took more than 325 mg of aspirin did have a high risk of bleeding.

That, in conjunction with the 2010 Dietary Guidelines for Americans, was enough to convince me to combine 81mg of aspirin in the morning with 0-3 US standard drinks in the evening at an average of 1.0/day. I'd like more information, but I haven't had time to dig it up yet and combining them seemed like a lower-risk provisional decision than inaction.

I recommend you do your own research and talk to your doctor, but maybe someone will find that information to be a helpful starting point.

Comment author: Alicorn 19 May 2011 05:24:41AM *  0 points [-]

As a result, while I used to occasionally take ibuprofen for headaches, when I began low-dose aspirin I stopped doing that. Now, when I have a rare headache, I'll take full-strength aspirin.

I would consider this significant reason to not take aspirin regularly. Ibuprofen decisively zaps my (frequent) headaches in a way that other analgesics do not.

Comment author: [deleted] 19 May 2011 06:16:02AM 2 points [-]
  1. Have you tried aspirin specifically for headaches?

  2. I'm not a doctor, so I can't diagnose anything, especially over the Internet (unless the patient is a C++ program), but it's possible for headaches to have a root cause that should be addressed, instead of the symptoms. In my case, getting a plastic nightguard from my dentist to prevent unconscious teeth grinding at night, also alleviated jaw clenching at night - so much so that when I make the effort to brush my teeth and wear my nightguard (which is unfortunately not all the time) I almost never wake up with a headache anymore.

  3. I can't think of a way to say this without sounding snarky (and I really liked Luminosity/Radiance, so I especially don't want to be rude), but I'm going to say it anyways:

Which do you dislike more: headaches, or cancer? Choose carefully.

Back to being non-snarky: I assume/hope that debilitating, world-shattering migranes aren't the issue - faced with them, "screw cancer reduction, I need to be able to function day-to-day" would be an entirely rational response. Interestingly, I just noticed this (and a typo) at Wikipedia: "There is some evidence that low-dose asprin has benefit for reducing the occurrence of migraines in susceptible individuals.[67][68][69][70]"

Comment author: Alicorn 19 May 2011 06:44:28AM *  4 points [-]

I do not have debilitating, world-shattering migraines. I just get headaches. More days than not. I have one right now. My mom once had a headache for an entire year. (This remains a medical mystery.) I have on occasion had headaches that lasted so long that I expected to imitate her, although so far I don't think I've actually broken a full week (with breaks provided by ibuprofen).

I actually don't usually medicate them. I do that when they are so bad that they wake me up in the middle of the night, or when they occur early in the day; otherwise I let sleep take care of them.

The one time I tried aspirin for pain relief, I don't remember what it was for, although a headache was likely. I do remember that it gave me a stomachache which was worse than whatever it was supposed to get rid of for me. I wouldn't expect a tiny dose to have this effect, especially if I took it with food or something, but if I were forced to rely on it as my only analgesic, I would be in something of a quandary.

The question is not, "Which do you dislike more: headaches, or cancer?" It's, "Which do you prefer: effective pain relief for your extended, commonplace pain, or a risk-reducing drug which has not actually been extensively tested in your gender or age group?"

Comment author: [deleted] 19 May 2011 06:57:14AM 2 points [-]

Fair enough - if I were in your shoes I would probably make the same decision as you.

Comment author: Alicorn 19 May 2011 07:13:21AM 0 points [-]

All that said: is taking aspirin regularly and an ibuprofen once a week inferior to not taking aspirin regularly and an ibuprofen once a week?

Comment author: [deleted] 19 May 2011 12:09:30PM 0 points [-]

I don't know. Wikipedia says:

According to the U.S. Food and Drug Administration, "Ibuprofen can interfere with the antiplatelet effect of low-dose aspirin (81 mg per day), potentially rendering aspirin less effective when used for cardioprotection and stroke prevention." Allowing sufficient time between doses of ibuprofen and immediate release aspirin can avoid this problem. The recommended elapsed time between a 400 mg dose of ibuprofen and a dose of aspirin depends on which is taken first. It would be 30 minutes or more for ibuprofen taken after immediate release aspirin, and 8 hours or more for ibuprofen taken before immediate release aspirin. However, this timing cannot be recommended for enteric-coated aspirin. But, if ibuprofen is taken only occasionally without the recommended timing, the reduction of the cardioprotection and stroke prevention of a daily aspirin regimen is minimal.[19]

Which of course doesn't mention the cancer effects, but there you go.

My intuition suggests that regular low-dose aspirin and weekly ibuprofen still has benefits that outweigh the risks, as compared to weekly ibuprofen only. However, my intuition didn't expect the effect, mentioned in the study's full text, where alternate-day low-dose aspirin appeared to have no effect on cancer.

Comment author: jimrandomh 19 May 2011 01:28:42PM 1 point [-]

I do not have debilitating, world-shattering migraines. I just get headaches. More days than not. I have one right now. My mom once had a headache for an entire year. (This remains a medical mystery.) I have on occasion had headaches that lasted so long that I expected to imitate her, although so far I don't think I've actually broken a full week (with breaks provided by ibuprofen).

Based solely on this description, this sounds like a pretty big deal. It also sounds like the sort of thing that might have a subtle but simple cause, which might be discovered by taking sufficiently detailed notes. I haven't tried it myself, but I recall seeing references to software for this purpose, which might suggest specific things to investigate as possible causes. Are your headaches by any chance related (positively or negatively) to eating choline? Would you be able to detect if there were other relations of that type?

Comment author: Alicorn 19 May 2011 06:38:21PM 0 points [-]

I tracked my headaches for about a month and a half once and then stopped, but I didn't correlate it with food (particularly not choline, which I don't even know what foods it comes in). I haven't noticed any decisive correlations between various foods and the headaches. I got one yesterday evening (a rare overnighter, which I'm waiting for the ibuprofen to chase away now) and that day I had leftover vegetable strata and juice and toast with hummus and some ice cream, none of which are or contain unusual foods for me.

Comment author: jimrandomh 19 May 2011 06:58:24PM 1 point [-]

There's lots of choline is in meat and eggs, and there're smaller qantities of it in various other things. I've heard of headaches from both too much choline (when taking choline supplements) and too little (especially when taking piracetam, which depletes choline. I take both piracetam and choline citrate). Being a vegetarian is listed as a risk factor for deficiency on the wikipedia page.

Comment author: Alicorn 19 May 2011 07:03:10PM 2 points [-]

I've been eating a lot of eggs lately. Should I try eating eggs every day for a week and then no eggs for a week and see what happens?

Comment author: jimrandomh 19 May 2011 07:12:56PM 3 points [-]

That sounds like a worthwhile experiment. I would also suggest keeping a headache log and a food log (there are cell phone apps to make it easy; you photograph things instead of writing them down) and analyzing them after a month or two.

Comment author: LukeStebbing 19 May 2011 04:39:07PM *  0 points [-]

There's also paracetamol (secret identity: acetaminophen (secret secret identity: tylenol)), which is not an NSAID, but I would guess you've tried it too. Fun snacks and/or facts:

http://en.wikipedia.org/wiki/Paracetamol

Until 2010 paracetamol was believed to be safe in pregnancy (as it does not affect the closure of the fetal ductus arteriosus as other NSAIDs can.) However, in a study published in October 2010 it has been linked to infertility in the posterior adult life of the unborn.

recent research show some evidence that paracetamol can ease psychological pain

ETA: I just remembered two important contraindications: Don't take more than 2g/day if you drink alcohol, and consider not taking more than 650mg at a time, since that's the FDA's revised recommendation after the old max dosage was shown to alter liver function in some healthy adults.

Comment author: Alicorn 19 May 2011 06:29:09PM 0 points [-]

Tylenol works about as well as other non-ibuprofen analgesics, which is to say it makes the headaches fade rather than go the hell away.

I don't drink alcohol ever, so that's not an issue.