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This isn't an anti-aging strategy, but it is an anti-death strategy: low-dose aspirin. As explained in this New York Times article on December 6, 2010, "researchers examined the cancer death rates of 25,570 patients who had participated in eight different randomized controlled trials of aspirin that ended up to 20 years earlier".
Eight. Different. Randomized. Controlled. Trials. Twenty-five thousand people.
They found (read the article) that low-dose aspirin dramatically decreased the risk of death from solid tumor cancers. Again, this ("risk of death") is the gold standard - many studies measure outcomes indirectly (e.g. tumor size, cholesterol level, etc.) which leads to unpleasant surprises (X shrinks tumors but doesn't keep people alive, Y lowers cholesterol levels but doesn't keep people alive, etc.). Best of all is this behavior: "the participants in the longest lasting trials had the most drastic reductions in cancer death years later."
Not mentioned in the article is the fact that aspirin is an ancient drug, in use for over a century with side effects that, while they certainly exist, are very well understood. This isn't like the people taking "life-extension regimens" or "nootropic stacks", who are, as far as I'm concerned, finding innovative ways to poison themselves.
Yet the article went on to say this:
I'm a programmer, not a doctor - but after looking around, I concluded that the risks of GI bleeding were not guaranteed fatal, and the risks of hemorrhagic strokes were low in absolute terms. Also, aspirin is famously effective against ischemic strokes. According to Wikipedia: "Although aspirin also raises the risk of hemorrhagic stroke and other major bleeds by about twofold, these events are rare, and the balance of aspirin's effects is positive. Thus, in secondary prevention trials, aspirin reduced the overall mortality by about a tenth."
So unless aspirin's risks are far more grave than I've currently been led to believe, as far as I'm concerned, people saying "hey, even if you're not subject to aspirin's well-known contraindications, you shouldn't start low-dose aspirin just yet" are literally statistically killing people. Cancer is pretty lethal and we're not really good at fixing it yet, so when we find something that can really reduce the risk (and there aren't many - the only other ones I can think of are the magical substances known as not-smoking and avoiding-massive-doses-of-ionizing radiation), we should be all over that like cats on yarn.
I make damn sure to take my low-dose aspirin every day. I started it before reading this article on the advice of my doctor who thought my cholesterol was a little high - I'm almost 28, so it'll have many years in which to work its currently poorly understood magic.
That said, this reduces the risk of one common cause of death (two or three if you throw in heart attacks and ischemic strokes). There are lots of others out there. Even if you could avoid all of them (including the scariest one, Alzheimer's - it's insanely common, we have no fucking clue what causes it or how to stop it, and it annihilates your very self - even if cryonics is ultimately successful, advanced Alzheimer's is probably the true death), humans pretty clearly wear out with an upper bound of 120 years. Maybe caloric restriction can adjust that somewhat. But I think I'll sign up for cryonics sooner rather than later - I'm in favor of upgrading probability from "definitely boned" to "probably boned but maybe not".
The meta-analysis you cite is moderately convincing, but only moderately. They had enough different analyses such that some would come out significant by pure chance. Aspirin was found to have an effect on 15-year-mortality significant only at the .05 level, and aspirin was found not to have a significant effect 20-year-mortality, so take it with a grain of salt. There was also some discussion in the literature about how it's meta-analyzing studies performed on people with cardiac risk factors but not bleed risk factors, and so the subjects may have been better candidates for aspirin than the general population.
The Wikipedia quote you give is referring to secondary prevention, which means "prevention of a disease happening again in someone who's already had the disease". Everyone agrees aspirin is useful for secondary prevention, but there are a lot of cases where something useful for secondary prevention isn't as good for primary. In primary prevention, aspirin doesn't get anywhere near a tenth reduction in mortality (although it does seem to have a lesser effect).
I would say right now there's enough evidence that people who enjoy self-experimentation are justified in trying low-dose aspirin and probably won't actively hurt themselves (assuming they check whether they're at special risk of bleeds first), but not enough evidence that doctors should be demonized for not telling everyone to do it.
Can you provide your reference for this? I looked at the meta-analysis and what I assume is the 20-year follow-up of five RCTs (the citations seem to be paywalled), and both mention 20-year reduction in mortality without mentioning 15-year reductions or lack thereof.
Edit: Never mind, I found it, followed immediately by
I'd like to see 20-year numbers for people who maintained the trial (and am baffled that they didn't randomly select such a subgroup).
Their selection methodology on p32 appears neutral, so I don't think they ended up with cherry-picked trials. Once they had their trials, it looks like they drew all conclusions from pooled data, e.g. they did not say "X happened in T1, Y happened in T2, Z happened in T3, therefore X, Y, and Z are true."
"Cancer is pretty lethal and we're not really good at fixing it yet, so when we find something that can really reduce the risk (and there aren't many - the only other ones I can think of are the magical substances known as not-smoking and avoiding-massive-doses-of-ionizing radiation), we should be all over that like cats on yarn."
Maintaining moderately high blood levels of vitamin D may reduce over all cancer rates by up to 30%. There is also evidence for green tea significantly reducing cancer rates.
Aspirin is an anti-coagulant so wounds take longer to stop bleeding. A surgeon will require that you stop taking aspirin long enough for the blood clotting factors to recover. (Surgeons hate it when they can't stop the bleeding.) If I were under 30 I wouldn't take a daily aspirin as I doubt it provides any benefit and does increase risk slightly. By the time you are 40 your body tissues are in a state of mild, chronic inflammation. That may be good for fighting off infections but isn't so good for the cardiovascular system, lungs, and brain. I recommend baby aspirin for anyone over 40.
Moderate alcohol use is correlated with a significant reduction in cardiovascular events. As with aspirin I would only recommend it for older people and then only if the likelihood of abuse is small.
I haven't seen thoroughly convincing studies, but it's quite possible that I missed them (among the blizzard of junk studies).
This is true, although I've noticed no significant effects. (When the air is cold and dry, I'm sometimes prone to nosebleeds, but they didn't get worse after I started low-dose aspirin).
It's also a bug and a feature. Heart attacks and ischemic strokes are no fun at all.
Not a problem for elective surgery (just stop taking it). If you need immediate surgery (e.g. because of an accident), then low-dose aspirin may be a slight risk - but it doesn't transform you into an instant hemophiliac.
Eight different randomized controlled trials suggest you're wrong. I'm unsure as to whether they studied relatively young adults like me - the problem is that it'd take even more decades to notice an effect. I consider aspirin's effects in older men to be persuasive evidence that it has the same effects for women and younger men like me. (In fact, as I mentioned, my doctor saw my slightly elevated cholesterol and told me to start fish oil and low-dose aspirin when I was 25 - it was only later that I saw the article about cancer.)
Citation needed. Do you really think that, in your 20s and 30s, your cells aren't accumulating damage that eventually leads to cancer, so that low-dose aspirin has nothing to prevent? Really? It's possible that the cumulative damage hypothesis, for lack of a better name, is false, but I consider it overwhelmingly likely to be true.
Obviously, in making this decision, my own health is at stake - and I am very careful. In my judgment, trying to be as rational as possible, I believe that the risks of starting low-dose aspirin in my 20s are very small, and outweighed by the cumulative benefit, when I'm older, of having taken it for so long (the time-dependent nature of the benefit is important).
"Eight different randomized controlled trials suggest you're wrong."
If the studies were done 20 years ago my guess is that the original trials were performed to see if aspirin reduced the risk of heart attacks. (At least that is what I recollect from that time period.) I doubt there were many people under 30 in those trials. I saw no indication in the linked article that ages were broken out so that one could determine whether people in their 20s who took aspirin for several years had less cancer 20 years later. Since few young people would be expected to get cancer I doubt the studies show that people in their 20s developed significantly fewer cancers from taking aspirin. My guess is that most of the people in the studies were men in their 40s, 50s, and 60s, i.e., those most at risk of heart attack.
"Do you really think that, in your 20s and 30s, your cells aren't accumulating damage that eventually leads to cancer, so that low-dose aspirin has nothing to prevent?"
My opinion is that the typical young person under 30 who doesn't abuse their body by smoking or excessive drinking has sufficient mechanisms to repair molecular damage so that aspirin will provide no additional benefit. Metabolism causes damage but it only becomes a problem when the body systems have deteriorated to the point where the body no longer keeps up with the damage done.
I believe that the cancer and Alzheimer prevention benefits from aspirin are due to reducing inflammation. I doubt people in their 20s typically experience mild chronic inflammation so I doubt aspirin will be beneficial. (I don't have specific papers to cite. This is just my impression from reading about cancer, Alzheimer's Disease, and inflammation for decades. I suspect you could find papers that discuss increasing inflammation levels with age and other papers that discuss the connection between inflammation and cancer and AD and other papers that discuss aspirin and inflammation reduction.) By their 40s such inflammation is common. For people in their 30s I viewed it as a toss-up.
I doubt most people in their 20s or 30s will be troubled by cancer or Alzheimer's Disease. There should be effective cures and preventative measures long before they are at significant risk.
Yes. The study's full text said: "We therefore determined the effect of aspirin on risk of fatal cancer by analysis of individual patient data for deaths due to cancer during randomised trials of daily aspirin versus control (done originally for primary or secondary prevention of vascular events) in which the median duration of scheduled trial treatment was at least 4 years."
Hope is not a plan.
I don't know if this is original, but it reminds me of the unofficial motto of Google's Site Reliability Engineering organization: "Hope is not a strategy."
First I heard this phrase was a book by the Army chief of staff: Hope is not a method.
Hm? No, that's about as official as we have.
Vitamin D is really important. There is an established causal link between vitamin D and immune function. It doesn't just enhance your immune response - it's a prerequisite for an immune response.
Anecdote: Prior to vitamin D supplementation, I caught something like 4 colds per year on average. I'm pretty sure I never did better than 2. I started taking daily D supplements about a year and half ago, and caught my first cold a few days ago. It's worth taking purely as a preventative cold medicine.
I wonder how the aspirin trials would look in regular people (I haven't checked, are any of your randomized trials in normal people?). Mike Darwin on aspirin;
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?
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.
Fascinating - I learned several things from the full text. Have an upvote!
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.
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:
p. 36:
p. 39:
and
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.
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.
The NYT linked to its abstract at The Lancet's website. The full text is behind a paywall.
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.
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:
that the nasty interactions only seemed to happen at 21+ drinks per week, sample:
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.
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.
Have you tried aspirin specifically for headaches?
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.
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]"
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?"
Fair enough - if I were in your shoes I would probably make the same decision as you.
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?
I don't know. Wikipedia says:
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.
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?
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.
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.
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?
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
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.
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.
And I think I have my answer:
http://well.blogs.nytimes.com/2012/01/16/daily-aspirin-is-not-for-everyone-study-suggests/
Thank you, very interesting.
From the abstract at:
http://archinte.ama-assn.org/cgi/content/abstract/archinternmed.2011.628v1
I am suspicious of the 6-year followup. In the original paper linked elsewhere in this comment tree, the observed reduction in cancer mortality grew over time.
I would be more willing to believe this new study if it followed patients for a longer period of time, observed the reduction in cancer mortality, and still concluded that the risks outweighed the benefits.
I'd like to point out that this pooled analysis of healthy people covered more than 4 times as many healthy people as your original citation covered sick people.
Do you think that the "sick people" were somehow susceptible to cancer in an aspirin-prevention-friendly manner, while the "healthy people" weren't?
(I am considering cancer separately from cardiovascular disease and bleeding risks, as they can be analyzed separately before overall risk-benefit is determined. I would not be surprised to learn that aspirin is very effective at reducing cardiovascular disease among those at risk, while not being worth it for cardiovascular disease among the general population.)
I'll try again: your original cite said the cancer benefit was detectable at 5 years, and later. I've presented you with a 4 times larger study, in the relevant subpopulation, at 6 years which found no cancer benefit - and you are still asking rhetorical questions and coming up with excuses.
Do you think that if you had seen the evidence the other way around that you would be asking the same questions?
No matter which study I saw first, the other would be surprising. A 100k trial doesn't explain away evidence from eight trials totaling 25k. Given that all of these studies are quite large, I'm more concerned about methodological flaws than size.
I have very slightly increased my estimate that aspirin reduces cancer mortality (since the new study showed 7% reduction, and that certainly isn't evidence against mortality reduction). I have slightly decreased my estimate that the mortality reduction is as strong as concluded by the meta-analysis. I have decreased my estimate that the risk tradeoff will be worth it later in life. I have very slightly increased my estimate that sick people are generally more likely to develop cancer and aspirin is especially good at preventing that kind of cancer, but I mention that only because it's an amusingly weird explanation.
If this new study is continued with similar results, or even if its data doesn't show increased reduction when sliced by quartile (4.6, 6.0, 7.4 years), I would significantly lower my estimate of the mortality reduction.
I'll continue to take low-dose aspirin since my present risk of bleeding death is very low, and if the graphs of cumulative cancer mortality reduction on p34 of the meta-analysis reflect reality, I'll be banking resistance to cancer toward a time when I'm much more likely to need it. I can't decide to take low-dose aspirin retroactively.
It doesn't have to, since they are not trials involving the same populations.
Perhaps I'm misunderstanding the numbers ("OR, 0.93"), but the new study observed a 7% decrease in cancer mortality, which they called "not significant".
I would be unhappy with the other study's population, but very happy with its followup period. (The fact that the observed benefit grew with the length of time taking aspirin was especially convincing, as I mentioned earlier. That is a property that is very unlike "maybe we're seeing it, maybe we're not" noise at the threshold of detection.)
Last year, I told you that polio had no natural reservoirs, and you continued to believe otherwise, so I am not especially inclined to argue further.
No, that's correct. If you want to use stuff that doesn't reach significance, I can't stop you. (You didn't reply to Yvain's points, incidentally.)
And you misunderstood the point about carriers defeating eradication attempts.
Is a regular dose of low aspirin something that my doctor should be informed about in case she wants to prescribe contraindicative medications at some point in the future (are there any?) or is it so harmless that I don't even need to update her? What low dose is indicated?
I didn't mean to imply that "you should do this now without telling your doctor". You should certainly tell your doctor about all the medications you're taking! I would even say that "ask your doctor immediately whether this is a good idea" is a reasonable approach(1), in contrast to the inexplicably indifferent tone of the article - although I'm sure the writer and editors have processed a zillion "observational study on a limited number of people for a limited amount of time indicates that X may have some influence on Y which ultimately leads to Z" articles, where the correct action in response really is to say "yes, that's nice, tell me when you know more".
The most significant caveat mentioned in the article was: "While Dr. Jacobs said the study design was valid, relatively few women were included in the trials, making it difficult to generalize the results to women." I'm male, so that one didn't apply to me. But look down a few paragraphs in the article: "who did an observational study several years ago reporting that women who had taken aspirin regularly had a lower risk of ovarian cancer". Even if I were female (it must be frustrating to have studies commonly ignore the half of the population that you're a member of(2)), I'd take the sum of this evidence as arguing in favor of starting low-dose aspirin.
"The specific dose of aspirin taken did not seem to matter — most trials gave out low doses of 75 to 100 milligrams"
As I recall from looking around the Internet, full-strength aspirin sizes vary around the world - in the US, Bayer sells 325mg pills, while I remember seeing that 300mg was common elsewhere. The low-dose aspirins also seem to vary as a consequence: 325/4 = 81.25, 300/4=75.
Although I would say that if you explain the study to your doctor, and they tell you that you shouldn't do it, and they can't explain why other than vague and unspecified risks, in the face of damn solid evidence - that you should get a new doctor.
On the other hand, it must be nice to have 5.2 additional years of life expectancy at birth. On the third hand, wow, I had forgotten that the difference was that large. On the fourth hand, some of that is due to men more commonly doing stupid things (like smoking) that I don't do.