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JosephBuchignani comments on Announcing the Quantified Health Prize - Less Wrong
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I've been struggling for some time with the issue of how to know what and whom to believe when it comes to lifestyle medicine (the effects of nutrition, supplements, exercise, etc. on health on longevity)... and it has occurred to me that I'm ignoring the elephant in the living room. As I understand it, the one non-obvious lifestyle change for which there appears to be good evidence of a very strong effect on longevity is caloric restriction.
When I first heard about CR over twenty years ago there were already decades of research demonstrating its apparently universal efficacy in extending the lives of mice and other short-lived creatures, and the case for CR has only gotten stronger since then as research has progressed to longer-lived creatures. It is arguably misguided to spend a lot of effort trying to figure out the right supplements to take (given the equivocal nature of much of the evidence) if you haven't yet made CR part of your lifestyle.
Longevity is not the only factor of interest.
There's CR and CR. A paleo lifestyle will greatly increase natural tolerance to fasting, leading to longer periods without meals, up to one day at times. Deliberate CR is something different.
CR doesn't show up among blue zones or the world's oldest people. Rather, the opposite - enjoyment of life.
I read a chimp study that showed CR chimps lived longer but had terrible quality of life compared to the fat happy sly contented ad libitum eaters. That suggests it's a tradeoff between living longer slowly and living faster richly.
Longevity is extremely hard to study in humans and there are many better-established effects on health from altering biological inputs than anything related to longevity.
Most importantly, cages and unnatural diets may tend to exaggerate the positive effects of CR on animals. Now interestingly, many humans live in the modern equivalent of cages and eat highly unnatural diets...
Therefore, I reject your thesis that rejecting CR and pursuing supplementation is misguided.
Or living at all: http://junkfoodscience.blogspot.com/2009/07/calorie-restrictive-eating-for-longer.html
The article is not entirely accurate. There are numerous claims that are easily refuted.
Okay. Is the central point correct?
The central point of that review? No, I don't think so. It is apparent from the ongoing rhesus monkey study that the calorie-restricted animals are much healthier and suffer fewer age-related frailties than the ad-libs.
Regarding CR showing up among blue zones or among the world's oldest people, I think the Okinawans are a fine example of mild-moderate CR in practice.
Then why wasn't total mortality lower?
Were. http://articles.sfgate.com/2004-04-04/news/17420824_1_urasoe-japan-naha-okinawa :
More recent; "An Age of Centenarians ? Lifelong Learning Policies and Ageing" slide 18
Well, it was. 21/38 control animals and 14/38 experimental animals had died when they published in 2009. The statistical significance of that is .16.
(Of course, if you extend the study, mortality becomes 100%. Why they measure this as mortality percentages rather than lifespan distributions is beyond me.) [EDIT] It looks like they do actually plan to report lifespan distributions, once all the subjects are dead.
So it doesn't make even the too-weak significance of p=.05.
Right, but I think that that's predominately because the sample size is small. We certainly can't conclude, from this evidence, that it does not affect mortality.
Right, but that strikes me as a failure of n. (They started this study with 30 monkeys; what the hell were they thinking? They expanded it to 76, but it's still too small.) It is noteworthy that the hazard rate of 3 for age-related deaths becomes only 1.5 when you look at all deaths. But what hazard rate do they expect controls to have relative to CR? If it's around 1.5, then they should have expected from the beginning that even if this study gave the modal result, it would not be statistically significant. For comparison, smoking has a hazard rate in the neighborhood of 2- which this study would have been too small to detect most of the time (as p=.03 for the age-related death hazard rate of 3, just below the .05 level).
When you look at the individual age-related causes, the differences are dramatic. 5/38 of the controls were diagnosed with diabetes, and 11/38 were diagnosed as pre-diabetic. 0 of the experimental animals developed diabetes (and going from 40% to 0% is a big jump!). Heart disease and cancer were both reduced by 50%. Age at first age-related diagnosis was significantly later in experimental animals (p=.008). 20% of the control group had been diagnosed with an age-related condition by the time the first experimental subject was diagnosed, and at age 30, when half of the control group was dead, 66% of the experimental group had not been diagnosed with an age-related condition, compared to 23% of the control group.* Even age-related lean muscle mass deterioration was less among the CR group.
It would be nice to know about energy levels, fragility, and so on, but from reading the study it seems pretty clear something is better about the CR group than the control group, and reasonable to suspect CR is better overall than neutral or worse. It's actually not even clear the CR group was more susceptible to injury, because the higher rates of non-age death among CR monkeys (9 instead of 7) could just be due to there being more CR monkeys (since more of the controls are buried).
* I suspect that if an animal died from a non-age cause, it is recorded as never developing an age-related disease. If you assume the best for the control group- that everyone who died was old first- and the worst for the experimental group- everyone who died wasn't old first- then you get 23% unaged in the control and 30% unaged in the experimental group, which is still striking. If you assume things are more even, then CR wins by a large margin.
How do you measure health, and what do you mean by "very clear"? I think there's general agreement that CR makes age-related deaths less likely. The concern is that it might do that by making other forms of death more likely. If I'm less likely to develop diabetes but more likely to fall / injure myself when I fall, I'm looking at a careful cost-benefit analysis, not a "woo less diabetes." In that light, the lack of statistical significance for mortality taking all causes into consideration is significant.
(I was going to comment on the monkeys living easy compared to humans, but it looks like 2/3 of the control group that have died have done so for age-related reasons, which is the same estimate I've seen for humans.)
Overall, it looks like the monkeys benefit from CR, but with the tiny sample it's hard to say how much, and without a discussion of their lifestyle / disease burden it's hard to say how it will generalize to humans living in the wild.
[EDIT]I had not read the full study when I wrote this comment. Now that I have, I am no longer worried about the lack of statistical significance. The study was so small that it couldn't have reliably detected a hazard the size of smoking. The arrows from this study all point towards CR being better, but they're very fuzzy arrows, and so we can't draw any firm conclusions.
Thanks for the link. That's information I hadn't encountered before. Sounds like the case for CR isn't as strong as I thought.
It also sounds like most or all of the benefits of CR can be had via intermittent fasting.