The eternal question of calorie restriction

By Razib Khan | August 29, 2012 9:22 pm

There’s a lot of buzz about a new paper in Nature (yes, I know there’s always buzz about some Nature paper or other), Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. You’ve probably heard about calorie restriction before. For me the issue I have with it is that people who are very knowledgeable (i.e., researchers who know a great deal abut human physiology, etc.) have given me contradictory assessments of this strategy of life extension. But it’s not totally crazy, there are serious scientists at top-tier universities who practice calorie restriction themselves. This isn’t the final word, but I wouldn’t be surprised if it is going to take decades for it to resolve itself for humans specifically (because some people will always be, and perhaps rightly, extrapolating from short-lived organisms to humans when it comes to modulations of lifespan in the laboratory).  The New York Times piece had a really strange coda:

Dr. de Cabo, who says he is overweight, advised people that if they want to try a reduced-calorie diet, they should consult a doctor first. If they can handle such a diet, he said, he believes they would be healthier, but, he said, he does not know if they would live longer.

Some scientists still have faith in the low-calorie diets. Richard Weindruch, a director of the Wisconsin study, said he was “a hopeless caloric-restriction romantic,” but added that he was not very good at restricting his own calories. He said he might start trying harder, though: “I’m only 62. It isn’t too late.”

Then there is Mark Mattson, chief of the laboratory of neurosciences at the National Institute on Aging, who was not part of the monkey study. He believes there is merit to caloric restriction. It can help the brain, he said, as well as make people healthier and probably make them live longer.

Dr. Mattson, who is 5-foot-9 and weighs 130 pounds, skips breakfast and lunch on weekdays and skips breakfast on weekends.

  • biologist

    Caloric restriction (CR) is probably not a single unified biological process, but rather a range of processes with overlapping causes and effects. By way of analogy, think of “cancer”.

    A good example is intermittent fasting (IF) described by Dr. Mattson. It is probably quite different in effect and mechanism than other kinds of CR even though they all involve dietary modification.

  • Razib Khan

    in keeping with the tone of discourse

    1) have you gotten fat?

    2) if not, has it been via calorie restriction? :-)

  • Dan

    Hyperlinked to wrong NYT link – but yes, I thought the end of that NYT article was also very strange…

  • zach

    strange ending but they could be alluding to a point -> modern doctors are not very good nutritionists and don’t really learn much about nutrition in med school and don’t conduct much nutrition research. Should you really take nutrition advice from a fat doctor?

    I feel that this is a valid point of the “do as I say, not as I do” variety.

  • Antonio

    My comment is a little off-topic but it called my attention that the meals skipped by the individual in the example are the first ones rather than the dinner. For a foreigner, It sounds really damaging this american practice of skying the earlier meals and thus only or mostly eating at night. My experience in parts of South America and Europe is that exactly the opposite should be true. You eat more as you are active and less closer to bedtime. These populations are healthier than US so one maybe attempted to do causal claims – which I is difficult in observational studies since many of the other confounding factors are different as well. Anyway, many studies have been conducted to evaluate whether particular sets of foods are healthier than others but I haven’t seen any that check the time of the calore intake. That would be quite interesting given observed differences among these populations.

  • DK

    My semi-educated guess is that *severe* calorie restriction is likely to prolong life for many – but, alas, that life is going to be miserable for almost everyone. No, thank you. Besides, my life is not something very worth of extending – and so is almost everyone else’s.

  • Markk

    The whole calorie restriction issue points up how science popularizaton very often fails. It almost always ends up being a full population generalization instead of really presenting a model and talking about what is supported and not supported.

    On the one hand, if a majority of a population is overweight, and being overweight leads to more chance of bad health and shorter lives, then in general calorie restriction would lead to better health and longer lives. This is unexceptional and is pretty much what the Wisconsin study and others did. They compared sedentary primates who were given all the food they could ever want (it was always available), with calorie restricted ones. It is probably a fair reproduction of current American Society – and if told that way the results make perfect sense – If you are eating too much then eating less is healthier.

    The study (and others) were then used to bolster simple models from other experiments and are presented as “magic” calorie restriction = longer lives as opposed to presented with possible good predictable models. Presented in the press and other general communication.

    There are interesting models being proposed and mechanisms we are learning about, but the higher level of detail tends to get washed out or just picked up uncritically as a mechanism for the magic. Ah… ok morning rant over…

  • gwern


    I don’t think it’s a strange ending. If CR now looks more dubious in humans (as it does), and CR is a *very expensive* practice in time, energy, possibly quality of life, and other factors – the reasonable thing to do is be more interested in cheaper partially related alternatives, to lower the risk of wasting all that effort.

    And intermittent fasting/IF is nothing if not easy.

  • MDF, MD

    Personally, I am more inclined to pay attention to data from primates than data from mice. Such data is more likely to be applicable to humans.

    The best advice has always been, and always will be, eat moderate amounts and get at least moderate excersize on a regular basis.

    I tend to be very wary of fads, and that’s how severe calorie restriction seems to me.

    Also, is it really worth the theoretical and probably doubtful and minimal extra life span if you have to make your life miserable to extend it? For me, the answer is probably not.

  • Rashid

    The science may or may not be valid, but the æsthetics’s are scary. Just look at these pole-thin scarecrows.

    What’s more, they actually have a picture of a Howard Johnson’s hotel room as evidence of a conference amenity.

    Give me an earlier death please.

  • ackbark

    My question is that wild animals are not designed for the easy availability of food so when their calories are restricted would that not more accurately mimic their natural environment but free of competitors and predators, while humans must be at least partly selected for relative abundance, because that’s been the underpinning focus of civilization?

  • Sandgroper

    @10 – Well, that answers a question – they look like sh*t.

    @11 – Yes, but it’s a question of how much calories are restricted, isn’t it? You see someone with excessive body fat, it’s a bit of a no brainer to suggest they’d be better off reducing their caloric intake, preferably by cutting out ’empty’ calories they don’t need from booze and sugars, and getting some exercise.

    That’s not the same as someone who reduces his intake to the point where he is anorexic, but who gets zero exercise – I would need a lot of persuading that is going to make somebody live longer. It didn’t work for the monkeys. All he needs to do is wait until he is 70, fall over and fracture his pelvis, and that’s pretty much it.

  • Sandgroper

    And note that Mattson’s BMI is toward the lower side of ‘normal’, he’s not into the ‘underweight’ zone. I’m not a huge fan of BMI for assessing individual conditions, but imagine what he would look like if he really starved himself to get into the ‘underweight’ zone.

    The body needs muscles to function. Muscle is more dense than fat. If you have a healthy amount of muscle mass and normal bone density, it is impossible to have a BMI that low, even if your body fat % is so low it is having an adverse effect on your immune system or (if you are female) preventing you from menstruating.

  • ackbark

    12. What I was really trying to get at but was too shy to walk right up to, was to ask if it could be that people with a higher percentage of decent from early farming populations would have a different response to caloric restriction than people who have a higher percentage of decent from hunter-gatherer populations?

    I was thinking about this because I was just looking at Eurogenes Hunter Gatherer vs Farmer test at Gedmatch, where I do well at hunting and gathering.

  • Sandgroper

    @14 – Just caloric restriction, I don’t know. I think the whole thing is over-simplified, because it depends on calories from what, and what you are doing with them. The body processes calories from different sources in different ways, e.g. the response to sugars and the way the body processes sugars is different to the way it processes complex carbohydrates from e.g. white rice. (So, note, that would mean that the simple energy balance equation is an over-simplification – which I believe it is.)

    To turn your question around another way, Australian Aboriginal people (meaning all or mostly Aboriginal ancestry here) suffer a much higher incidence of Type 2 Diabetes associated with obesity than white Australians descended from agricultural societies, in response to a diet high in sugars and alcohol. The rate of Type 2 Diabetes is already now worryingly high among white Australians, but it is even much higher among Aboriginal people.

    The thing that interests me is that elite-level Australian footballers and boxers who are Aboriginal are very lean and muscular, even though they presumably eat as many sugars and refined carbohydrates and drink as much beer as their white counterparts, i.e. provided people are sufficiently physically active, ancestry doesn’t seem to make a difference, they are all lean, fit and muscular. So much for the answer being diet rather than exercise – it’s self-evidently both, plus genes.

    If you think you incline that way genetically, and you want to lose some body fat, your best strategy would be to avoid sugars, refined carbs and fats as much as you can manage without being fanatical, and get a balanced exercise program of cardio-vascular exercise (this could just be brisk walking if anything else is unmanageable), with some weight training to make sure you maintain muscle mass while you are losing fat. If you don’t do the weight training, then your body will just lose both fat and muscle mass, which is what happened to me when I was doing nothing but long distance swimming, which was aerobic.

    Going from a blimp to a skeleton is just trading one problem for another – unless you believe that being a skeleton will make you live longer. To me it’s somewhat irrelevant, quality of life over a decent span is what matters.

    Cutting out sugars is not that easy, though – with processed foods they put the damn stuff in just about everything, but as long as you are exercising enough, and accept that fat loss is a matter of being consistent over at least several months, you don’t need to be really fanatical about it – avoiding the obvious things that contain a lot of added sugar is probably good enough. And alcohol, the liver just converts ethanol into sugar.

  • Rashid

    @12 “All he needs to do is wait until he is 70, fall over and fracture his pelvis, and that’s pretty much it.”

    Yes, I would say that the morbidity (mortality?) rate from hospital infections due to anorexia-related injuries should be factored into their calculus.


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About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at


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