Real Life Extension: Caloric Restriction or Intermittent Fasting? (Part 1)


Can you slow the sands of time? The research say yes… but what’s the best option? (Photo: Thomas Ellis)

Most people don’t want to die.

Since even before Ponce de Leon and his search for the fountain of youth, man has been on a quest to achieve immortality.

Some people think we’re getting closer. In recent years, caloric restriction (CR) has been demonstrated to increase lab rat lifespans more than 20%. “Intermittent fasting” (IF), a much lesser-known and more lifestyle-friendly alternative, has shown results that even surpass CR in some respects.

Following up on the popularity of his last post on this blog (The Science of Fat-Loss: Why a Calorie Isn’t Always a Calorie), Dr. Eades examines these two options and his personal experiments with both.

If you want to live longer, this two-part article is an excellent place to start for avoiding common mistakes, pain and wasted effort.


Dr. Eades:

How would you like it if I told you there was a way to eat pretty much anything and everything you wanted to eat and still maintain your health? Or better yet, what if I told you that you could eat pretty much anything and everything you wanted and even improve your health? Would you be interested?…

There is a way to reduce blood sugar, improve insulin sensitivity, reduce blood pressure, increase HDL levels, get rid of diabetes, live a lot longer, and still be able to lose a little weight. All without giving up the foods you love. And without having to eat those foods in tiny amounts. Sounds like a late-night infomercial gimmick, but it isn’t.

When I wrote those words as the lede to an article about a year and a half ago, the idea of intermittent fasting was limited mainly to research scientists and faddists. But a number of studies had been published – primarily on rodents – showing that intermittent fasting led to a host of benefits that not even caloric restriction could claim.

And these weren’t studies published by no-name scientists laboring in backwater research departments. The lead author on many of these papers was Mark P. Mattson, Ph.D, the Chief of the Laboratory of Neurosciences and Chief of the Cellular and Molecular Neurosciences Section of the National Institute on Aging, a division of the National Institutes of Health. People were starting to take notice.

Before the work on intermittent fasting, the only real strategy for extending the lives of laboratory animals was caloric restriction (CR). If rats or mice or even primates had their calories restricted by 30-40 percent as compared to those fed ad libitum [“at pleasure” = as much as they want] they lived 20-30 percent longer. These studies are typically done by dividing genetically similar animals into two groups, then giving one group all the food it can eat in a day. Researchers measure the food consumed, then reduce it by 30-40 percent and give to the other group the next day. Each day this drill is repeated with the calorically restricted group getting a reduced amount of food compared to what the other group got the day before.

These CR verses ad libitum-fed studies almost uniformly demonstrate an increase in longevity in the CR animals. The CR animals not only live 30 percent or so longer, they don’t develop cancers, diabetes, heart disease, or obesity. And these animals have low blood sugar levels, low insulin levels, good insulin sensitivity, low blood pressure and are, in general, much healthier physically than their ad libitum fed counterparts. But not so psychologically.

As we saw in the Keys semi-starvation study, caloric restriction isn’t much fun for humans, and it apparently isn’t all that much fun for the animals undergoing it either. When rats live out their ratty lives calorically restricted in their cages, they seem to show signs of depression and irritability. Primates do as well. If primates don’t get enough cholesterol, they can actually become violent. But they do live longer. Even though CR has never been proven in humans, based on lab animal experience it does work. So, if you’re willing to put up with irritability, hostility and depression, it might be worth cutting your calories by 30 percent for the rest of your long, healthy miserable life.

But could there be a better way?

An enterprising scientist decided to try a little twist on the CR experiment. He divided the genetically-similar animals into two groups, fed one group all it wanted and measured the intake, then fed the other group all it wanted – except every other day instead of daily. When the intake of the group fed every other day was measured, it turned out that that group – the intermittently fasted group – ate just about double on the eat days, so that overall both groups consumed the same amount of food. Animals in the one group at X amount of food per day while the animals in the other group ate 2X amount of food every other day. So both groups ate the same number of calories but the commonality ended there.

The intermittently fasted group of animals despite consuming the same number of calories as the ad libitum fed group enjoyed all the health and longevity benefits of calorically restricted animals. In essence, they got their cake and ate it, too. They got all the benefits of CR plus some without the CR.

Intermittent fasting (IF) reduced oxidative stress, made the animals more resistant to acute stress in general, reduced blood pressure, reduced blood sugar, improved insulin sensitivity, reduced the incidence of cancer, diabetes, and heart disease, and improved cognitive ability. But IF did even more. Animals that were intermittently fasted greatly increased the amount of brain-derived neurotrophic factor (BDNF) relative to CR animals. CR animals don’t produce much more BDNF than do ad libitum fed animals.

BDNF, as its name implies, is a substance that increases the growth of new nerve cells in the brain, but it does much more than that. BDNF is neuroprotective against stress and toxic insults to the brain and is somehow–no one yet knows how, exactly–involved in the insulin sensitivity/glucose regulating mechanism. Infusing BDNF into animals increases their insulin sensitivity and makes them lose weight. Humans with greater levels of BDNF have lower levels of depression. BDNF given to depressed humans reduces their depression. And increased levels of BDNF improve cognitive ability. In short, you want as much BDNF as you can get, and with IF you – if you’re a lab animal at least – can get a lot.

As the animal study data poured in, a few researchers began tentatively studying human subjects. A few studies appeared in the literature, and all showed positive benefits to humans who intermittently fasted. In none of the studies did subjects go completely without food for a day – most had one meal per day or ate ad libitum one day and reduced consumption markedly the next.

Even some academic physicians (including Don Laub, my old mentor when I did a plastic surgery rotation at Stanford) put themselves on a modified version of an IF and wrote about it the the journal Medical Hypothesis. Since May 2003, these folks have been on a version of the IF in which they consume about 20-50 percent of their estimated daily energy requirements on the fast day and eat whatever they want on the non-fast days.

Since starting their regimen they have

observed health benefits starting in as little as two weeks, in insulin resistance, asthma, seasonal allergies, infectious diseases of viral, bacterial and fungal origin (viral URI, recurrent bacterial tonsillitis, chronic sinusitis, periodontal disease), autoimmune disorder (rheumatoid arthritis), osteoarthritis, symptoms due to CNS inflammatory lesions (Tourette’s, Meniere’s) cardiac arrhythmias (PVCs, atrial fibrillation), menopause related hot flashes.

It all sounded good. But before I try anything out of the ordinary, and certainly before I suggest it to any of my own patients or readers, I view the idea through the lens of natural selection. In other words, I ask myself if the regimen in question would have been congruent with our Paleolithic heritage. If so, I move forward. If not, I take a long, hard look at all the biochemistry, physiology and pharmacology involved before I make any sort of recommendation.

In viewing IF through the lens of natural selection I came to the conclusion that IF was probably the way Paleolithic man ate. We modern humans have become acculturated to the three square meals per day regimen. Animals in the wild, particularly carnivorous animals, don’t eat thrice per day; they eat when they make a kill. I would imagine that Paleolithic man did the same. If I had to make an intelligent guess, I would say that Paleolithic man probably ate once per day or maybe even twice every three days. In data gathered from humans still living in non-Westernized cultures in the last century, it appears that they would gorge after a kill and sleep and lay around doing not much of anything for the next day or so. When these folks got hungry, they went out and hunted and started the cycle again.

If you accept, as I do, that the Paleolithic diet is the optimal diet for modern man due to our evolved physiologies, then you should probably also buy into the idea that a meal timing schedule more like that of Paleolithic man would provide benefit as well.

With this in mind, I recruited my wife into the process and we went on an intermittent fast . It wasn’t all that difficult, but I can tell you that the non-eating days were long. And the eating days were spent eating and dreading the non-eating day soon to follow.

After a few weeks, it dawned on me that we weren’t really following the same IF that all the lab animals were. The lab animals got food for 24 hours then went without for 24 hours. We, on the other hand, got food for about 16 hours (the waking hours) then went without for about 32 hours (8 hours sleeping, 16 hours awake and the next 8 hours sleeping). We decided to modify our fasting strategy…

(Continued in Part II)

Related and Most Popular Posts:
How to Lose 20 lbs. of Fat in 30 Days… Without Doing Any Exercise
From Geek to Freak: How I Gained 34 lbs. of Muscle in 4 Weeks
The Science of Fat-Loss: Why a Calorie Isn’t Always a Calorie
Relax Like A Pro: 5 Steps to Hacking Your Sleep
How to Travel the World with 10 Pounds or Less (Plus: How to Negotiate Convertibles and Luxury Treehouses)
The Art of Letting Bad Things Happen (and Weapons of Mass Distraction)

Posted on: March 2, 2008.

Watch The Tim Ferriss Experiment, the new #1-rated TV show with "the world's best human guinea pig" (Newsweek), Tim Ferriss. It's Mythbusters meets Jackass. Shot and edited by the Emmy-award winning team behind Anthony Bourdain's No Reservations and Parts Unknown. Here's the trailer.

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53 comments on “Real Life Extension: Caloric Restriction or Intermittent Fasting? (Part 1)

  1. Definitely looking forward to part 2. I’ve done the CKD, your slow carb diet, and am now experimenting with a 40/40/20 diet while strength training.

    I find the extent of the human body’s malleability through fitness and nutrition to be quite fascinating. These articles and views definitely push the limits further than anywhere else I can get information, and they’re backed up by factual data at the result of specific experimentation rather than theory.

    Much appreciated.


  2. Hey Tim,
    I wondered when you’d come around to this topic.

    Having been a personal trainer for over ten years I had always been going along with the “eat 5 meals spaced out every 3 hours, etc”. It wasn’t till I started to read more and actually experiment on my own, that I realized “IF” worked fantastic for me.

    I train very hard (CrossFit) and my stamina and strength continue to be fine, while my body fat has lowered slightly. The biggest benefit is the time I save.

    Typically I fast most of the day, then eat 1 big meal at night. Mind you that the “big meal” is mostly Paleo, rarely do I eat junk.

    It may take little getting used to, but I encourage people to give it a try.


  3. Well, I should wait for part II I guess, but wouldn’t there be a genetic difference between the sexes? I would think the hunters (men) wold evolve as you describe, but what about the “gatherers” (women)? — and in a lot of cases, didn’t the hunters go back to the “cave” to sleep and possibly snack on the nuts and berries gathered while they (alternately) slept? In addition, wouldn’t the hunters’ diets consist more of the gathered (stored) food during cold months, when animals are harder to hunt (or perhaps, hunting is more difficult)? Just thinking out loud :)


  4. Tim,

    I whole heartedly believe in this theory. I’ve been “cleansing” for several years now. I don’t do the 1 day on, one day off, like what this article says. Instead, I do 1 day a week (sometimes every other week) of eating about 150 calories of very easily digestable food. I’m giving my body time to recover and get into balance again. That method has helped me lose over 30lbs and I’ve never felt better.

    Most people stuff themselves constantly the whole day and their body is overwhelemed with food. It doesn’t use anywhere near all the food it has and it becomes backed up and begins to break down. So absolutely, reducing caloric intake fasting is the way to go!



  5. I tried eating once a day, a huge meal in the evening. Other than that, I sipped protein all day to keep my lipids at a high level to avoid muscle degeneration. I lost a ridiculous amount of weight fast, but didn’t seem to lose any strength, which I track in a gym journal. I also did a HITT cardio workout before eating to put myself in the right mode to absorb the calories into my cells instead of storing them as fat. Food tasted much better, and eating the big meal was a treat, like a feast, rather than a chore, which eating sometimes feels like now.

    The problem was that by the time afternoon came around, I was completely brain dead from low blood sugar. I mean, I couldn’t string a sentence together I felt so dumb. I’m a writer, and I could do no work between early afternoon and my giant meal, and since I would pretty much fall asleep right afterwards, being dead tired from starving all day and then having 3000 calories in my swollen stomach, I wouldn’t do any work afterwards.

    I quit eating this way because I’m a hard gainer, and even the proponents of this “Warrior Diet” say a bodybuilder wouldn’t want to eat like this. Sometimes I’m tempted to take it up again because it is so much easier than eating all day long, but I’m in grad school and if I did, I’d have to make the transition during the summer, when I don’t have so much thinking to do. I think the dumbness would go away eventually.

    Some people report mental acuity as a benefit of this diet. It certainly didn’t have that effect on me.


  6. I’ve been eating an IF diet for years.

    I actually feel healthier since I started following the Warrior Diet guidelines for what order to eat foods in the over eating phase. I picked up a copy of Ori Hofmekler’s book on a whim and I’ve been so happy with having some guidance on how to eat intermittently and feel good.

    Check it out if you’ve been skipping meals and not feeling so hot afterwards.


  7. Hunter gatherer thought experiments make a lot of sense when it comes to diet but I think that sort of though experiment can be really contorted when it comes to gender studies and studies about the evolution of civilization. Think Thomas Hobbes and the State of Nature. I think there is a big limit to our thinking experiments and the empirical facts. In this case they align but I don’t see the empirical facts being wrong/harmful if they don’t align with the hunter/gatherer thought experiment.

    Just my 2 cents from studying some philosophy and arguing against Hobbes and Rawls.


  8. Hi Tim,

    Isn’t that the “Warrior Diet”? If you haven’t heard of it, try looking into it. It basically says to not eat until dinner, because that’s what “Warriors” (= Paleo hunters) would have done.

    Give it a try,



  9. Interesting stuff – curious as to how to stage training in with the fasting. obviously, it’s better to eat a little protein 2hrs before, maybe just hold on the bigger meals?

    It doesn’t seem to make much sense prolonging life if the quality goes down – people just love food – I have noticed that specific food is appreciated more when it isn’t eaten for awhile – it would be interesting to compare absorption rates of different meals and corresponding balances in the body after a fast period vs. a normal cycle.

    Thanks for the great post.


  10. I’ve been doing morning fast for a while. I’m just not hungry in the morning. Argued at length with my wife (who is med student) about it. I’ve heard that this can cause gall stones. Anyone else hear this?


    • I have been doing IF for about a month and yes, I have lost body fat and a few lbs. I eat low carb anyway, so the main meal is usually meat, fish, chicken ..then veggies, nuts, etc.
      My concern is that for the last week, I’ve been experiencing intermittent, dull pain under my right rib. I”m terrified that it could be a gall stone issue.
      I too, as Blogrdoc, am concerned about IF(or as mainstream would call ..crash dieting) would cause gall stones.
      Would someone please address this..thanks.


  11. Thanks Tim and Dr Eades, I find all of your health/diet articles very interesting and appreciate that you are willing to experiment against the norm. I Typically dont have my first meal of the day until late afternoon as I find that I am simply not hungry until then, and drinking water keeps me functioning most of the day. I have always maintained a constant body weight while not restricting at all the foods that i consume in the evening. The majority of my family is in the medical profession, Drs and Dietitians and they argue against me skipping breakfast but I feel I am healthier than any of them!

    I am looking forward to part II


  12. Interesting. Last Friday I embarked on my first fast-day further to the health benefits I had previously read about and experienced by accident after a bout of illness. I gorged on food in the late evening after drinking water spiked with aloe vera juice throughout the day. I am interested to read more about the science behind this. I believe the digestive system needs to rest and repair to make it work efficently and to temper the immune system. If it will increase the time I have with the people I love, all the better. An alternative approach is to only eat when you are hungry (biological) as opposed to craving (psychological).
    The food tastes better when you are hungry.

    comments odds and ends :P
    Can’t believe what i’m seeing appended to your blog! you’ve finally succumed to twitter!


  13. There was a diet floating around on bodybuilding boards about 5 years ago like this, “the warrior diet” as someone else pointed out. I believe you don’t completely fast though iirc. You eat very low amount of low-GI carbs through the day working up to the big feast at night.

    I think it’s a cool idea but I still don’t understand the necessary link between depression and low calorie diets. I think this bit is a subjective. I’ve been on several low calorie regimes for periods of time and am far from depressed. The fact that I am in complete control of what I eat and working toward a goal makes me happy not depressed! Some of the MOST depressing times in my life is when I’m eating “ad libitum”.


  14. It sounds feasible but I am wondering about two critical things here:

    -The fact that there probably is a positive relation between caloric restriction and IF with longevity in rodents does not mean that we can impose this, withouth constraints, on humans. How would you support this line of thinking?

    -Does this mean that, keeping all other factors constant, you can say that our paleolithic ancestors would have lived 30% shorter if they had adopted our dietary customs of eating thrice daily?

    Hoping to see your comments!


  15. actually, this makes sense because a 24 fast will eliminate insulin for 24 hours and free up the fat cells to mobilise the fat –

    however, as longevity specialist Cythnia Kenyon observed, it’s not total calories that reduces lifespan in animal models, but glucose. if you reduce the carbs, they live longer – the fat calories don’t lower lifespan. many researchers fail to distinguish the two for fear of contradicting the low fat dogma.

    here’s the extract from a New Scientist article profiling Cynthia’s career:

    “But for now, caloric restriction seems the one proven way to extend lifespan. Is that why you’ve virtually given up carbohydrates?

    That’s not necessarily why I do it. I do it because it makes me feel great and keeps me slender. And I don’t feel really tired after a meal. But I think if I wanted to eat in a way that extended lifespan this is how I would do it. In fact, I stopped eating carbohydrates the day we found that putting sugar on the worms’ food shortened their lifespans.
    How does it work?
    I eat a diet that keeps my insulin levels low. So, for example, at breakfast I have bacon and eggs with tomatoes and avocados. It’s bit like the Atkins diet. I don’t actually know if I eat fewer calories, but I feel great and I weigh what I did in high school. I certainly wouldn’t want to be hungry all the time, but I’m not, I’m never hungry. I tried caloric restriction just for two days but I couldn’t stand it, being hungry all the time.
    What don’t you eat?
    I don’t eat sweets, bread, pasta, potatoes or rice. I actually do eat lots of carbohydrates, just not starchy ones, the ones that turn into sugar quickly in your body. I eat lots of vegetables and salads, and lots of fish and nuts, cheese, eggs and meat. People are now studying these low-carb diets like Atkins and the zone diet scientifically”.
    for full text)



    Hi Markus,

    Excellent comment. I’ll be looking more into this as well.

    All the best,



  16. Tim,

    Have you tried this diet out? It sounds interesting. I think there may be some truth in that. Making your body go without food may help it to become more resistant. Great insights, thanks again.



    I do practice what you might call ICR — intermittent calorie restriction — and I also do IF when I am ill or becoming sick.