Monday, December 28, 2009

Intermittent fasting prolongs life in mammals

Although experiments have demonstrated that caloric restriction (CR) can extend lifespan in yeasts, worms, mice, and possibly primates, few people would want to pay the price of caloric restriction to extend life. The Caloric Restriction Society has a page listing the risks of CR, which include

-chronic hunger, cravings, or food obsession
-large loss of body mass, up to 25% below normal
-loss of strength
-low body temperature
-decreased testosterone
-menstrual irregularities
-slower wound healing
-loss of emergency energy reserves

When Ancel Keys did the Minnesota Starvation Study, he restricted young men to 1800 calories daily, 20-40% below average needs -- similar to recommendations for caloric restriction for longevity. His goal was to get the men down to 25% below normal weight -- the CR society also suggests reaching 10-25% below normal weight.

As reported in the Journal of Nutrition, one of the participants in this experiment, Harold Blickenstaff, "recalled the frustration of constantly thinking about food:

I don’t know many other things in my life that I looked forward to being over with any more than this experiment. And it wasn’t so much ... because of the physical discomfort, but because it made food the most important thing in one’s life ... food became the one central and only thing really in one’s life. And life is pretty dull if that’s the only thing. I mean, if you went to a movie, you weren’t particularly interested in the love scenes, but you noticed every time they ate and what they ate. found men depression, and other effects making for many a long life not worth living.

Energy restriction had numerous adverse effects in the Minnesota Study:

"They experienced dizziness, extreme tiredness, muscle soreness, hair loss, reduced coordination, and ringing in their ears. Several were forced to withdraw from their university classes because they simply didn’t have the energy or motivation to attend and concentrate."

The subjects of the Minnesota Starvation Experiment developed all the visible signs of starvation: "sunken faces and bellies, protruding ribs, and edema-swollen legs, ankles, and faces. Other problems such as anemia, neurological deficits, and skin changes became apparent." The men lost interest in sex, and had no functional energy.

Again from the Journal of Nutrition: "The St. Paul Dispatch reported: '... the ... men on the starvation diet have lost so much physically and mentally that their ambition is gone, their will to go forward is gone, and they cannot do heavy work such as farming, mining, forestry, lifting and many other types of work necessary to rebuild war-torn Europe.'"

So, if you choose caloric restriction, you might spend more years breathing, but would you call that living? Do we have a better way?

On the CR (Caloric Restriction) Society International website FAQ page you can find this:

“Are there any other ways of retarding biological aging or extending lifespan besides CR?

None known to science at this time. .. as of this writing, there is no reliable evidence to support the notion that anything besides CR is capable of retarding biological aging or extending maximum lifespan in adult mammals. “

Yet just above this statement, on the same page, you will find this:

Studies have shown that rodents fed all they can eat [emphasis added], but fasted every two, three or four days, also have an increase in longevity, though the increase is not quite as great as that of rodents on the standard kind of CR (when implemented in mature organisms). For some people, this might be an easier way of doing CR since hunger is limited to two or three days a week.

A humane approach to life extension research would look for a method that would not entail all of the harmful side effects listed above. I personally would not want to live a long, cold, depressed, constantly hungry, food-obsessed, neutered life having insufficient strength, muscle mass, or energy for activities I enjoy, and unable to heal wounds at a normal rate.

I think intermittent fasting can give you more life to live while preserving your ability to live it.

IF extends lifespans of Wistar Rats

In 1945, Anton J Carlson and Frederick Hoelzel of the department of physiology at the University of Chicago published “Apparent Prolongation of the Life of Rats by Intermittent Fasting” in the Journal of Nutrition. This paper detailed the results of their studies in which they put adult rats on intermittent fasting schedules of 1 fast day in 2 days, 1 in 3 days, and 1 in 4 days, compared to control animals allowed to eat ad libitum.

In this study, they fed the rats in four groups, three getting one of three different omnivorous diets and one getting a vegetarian diet.

The three omnivorous diets included:
1) A basic diet consisting of 61.5% cooked and dried whole veal (including practically all of the edible parts of calves, excepting excess fat and blood), 31 % corn starch, 2% powdered yeast, 1% cod liver oil, 1.5% inorganic salt mixture and 3% veal bonemeal. This diet provided 35% protein.
2) The basic diet (#1) plus 10% finely ground alfalfa stem meal.
3) The basic diet plus 5% psyllium seed husk and 5% specially prepared kapok fiber.

The one vegetarian diet consisted of 50% whole wheat flour, 10% peanut flour, 7% lima bean flour, 7% wheat gluten flour (containing 80% gluten), 7% corn gluten meal, 7% linseed meal, 5% powdered yeast, 5% alfalfa leaf meal and 2% NaCl. This diet provided approximately 30% proteins.

Hoelzel had previously performed a study in which he found that rats fasted every other day and fed a diet low in protein on non-fast days developed peptic ulcers within about 2 weeks, but rats fed adequate protein did not develop ulcers.

All groups got lettuce trimmings daily. During feeding periods, they supplied food continuously to all groups, so rats ate ad libitum when not fasting. Fasting began at 42 days (before which all rats received identical feed) and continued until the rats died.

Table 1 of the paper shows the effects on lifespan of fasting 1 day in 2, 3, or 4 days in male and female rats.

Fasting increased the average lifespan of males by 90 days, and that of females by 23 days.

Optimum fasting interval

Upon detailed analysis of their data, Carlson and Hoelzel found that rats fasting 1 day in 4 and 1 day in 2 displayed complications by “extraneous factors” more than either control rats eating ad libitum or rats fasting 1 day in 3. Those factors included:

1) The earliest male and female deaths occurred in the groups fasted 1 day in 4, and it appeared that other rats did not fare as well fasting 1 day in 4 as in 1 day in 3. Carlson and Hoelzel suggested that “Perhaps the amount of food consumed in 3 days of feeding, with increased voracity but without proportionately increased capacity after 1 day of fasting, constituted a greater physiological overstrain than the amount of food consumed by the controls or by the rats fasted 1 day in 3.”
2) Fasting 1 day in 2 produced both a greater mortality rate and the longest-lived rats. The males and females fasted 1 day in 2 also began dying earlier than the rats fasted 1 day in 3. Carlson and Hoelzel commented: “Evidently fasting 1 day in 2 and beginning this at the age of 42 days was too much fasting for some rats. One of the females fasted 1 day in 2 apparently died of a hemorrhage from a chronic duodenal ulcer.” Fasting 1 day in 2 produced the longest-lived male and female rats, 1052 and 1073 days respectively, but the average rat did very poorly on this level of fasting.

Carlson and Hoelzel concluded that the optimum amount of fasting for the average rat in their study was 1 day in 3, or about twice weekly. This fasting frequency produced a 15% increase of average lifespan for females and 20% for males.

Of interest, in their raw data (Table 1), the average lifespan of male rats fasted 1 day in 4 did not significantly differ from those fasted 1 day in 3. Females fasted 1 day in 3 actually on average lived longer than those fasted 1 day in 2, but the reverse for males.

Another way to interpret this: Fasting 1 day in 2 produced a restriction of calories that proved too harmful for the majority of rats. Fasting 1 day in 3 or 4 produced the optimum result without daily caloric restriction.

Taking the average lifespan of 75 years in the U.S., this would mean IF twice weekly could increase the span to 86 to 90.

IF did not affect growth

Whereas 40% CR adversely affects muscle growth and mass, in this study, Carlson and Hoelzel found no or only small effects on growth or body mass in rats fasted 1 day in 4 or 1 day in 3.

Under unrestricted feeding conditions, male Wistar rats reach 450-520 g, and females reach 250-300 g.

In this study Carlson and Hoelzel compared littermates fed ad libitum to those fasted 1 day in 2, 3, or 4 days.

Using litter mate controls, male rats fasted 1 day in 4 attained body mass 91% of males fed ad libitum (413 v. 449 g), those fasted 1 day in 3 attained 85% of the mass of ad libitum males (339 v 397 g), and males fasted 1 day in 2 attained 74% of the body mass of ad libitum littermates (265 v. 356 g).

Female rats fasted 1 day in 4 attained body mass 89% of ad libitum females, those fasted 1 day in 3 attained 89% of ad libitum females, and those fasted 1 day in 2 attained body mass 85% of ad libitum females.

Again using litter mate controls, in some cases fasted rats actually had longer femurs than rats fed ad libitum, illustrating that intermittent fasting did not impair healthy tissue growth. In contrast, as stated by the CR Society's Risks Page, "Physical growth may be impaired by calorie restriction, as observed in lab animals."

Genetic controls

Carlson and Hoelzel found a large variation in response to fasting and feeding regimens. All rats were Wistar variety, and regardless of regime, 67% of all rats died between ages of 550 and 850 days, and 85% between 400 and 900 days. Further, “Some littermate rats, after having been kept from 400 to 1000 days on widely differing nutritional regimens, died within 24 hours or a few days of one another. Four of the twelve rats that lived to be over 1000 days old belonged to one of the seventeen litters.” Thus, genetic factors played a strong role in mortality.

IF influence on development of disorders leading to death

Carlson and Hoelzel also found that fasting rats had retarded development of mammary tumors, both in terms of age of onset and size of tumor, proportional to the amount of fasting. The following table from their paper displays the data.

Mammary tumors occurred in 37% of ad libitum female rats, compared to 29% of females fasted 1 day in 4 , 36% of those fasted 1 day in 3, and only 7% of those fasted 1 day in 2.

Average weight of tumors in ad libitum females equaled 193 g, versus only 67 g in rats fasted 1 day in 4 and 36 g in those fasted 1 day in 3.

Rate of tumor growth was +134 g/100 days in ad libitum rats, +48 g/100 d in rats fasted 1 day in 4, +42 g/100 d in rats fasted 1 day in 3, and +13 g/100 d in rats fasted 1 day in 2.

IF extends healthy lifespan

Carlson and Hoelzel thus showed in 1945 that intermittent fasting 1 in 3 days extends healthy lifespan of rats by 15-20% compared to ad libitum feeding, without daily food restriction (hunger), restriction of protein intake (these rats had 30-35% protein diets), impairing healthy lean tissue growth, or causing extreme loss of body mass.

It looks to me like IF offers a rational alternative to daily caloric restriction.


Jeff said...

Hey Don,

Cool post.

I fast around 2 days per week and do a shorter feeding window on most other days. That said I always was skeptical about fasting/IF making a real difference for me as a strict Paleo eater. My concerns is with what it is comparing against. Fed a junk diet I would fully expect eating less junk to make a difference.

A few questions:
-If the comparison is with a more natural, wild diet do you think that IF would still increase lifespan 20% or so?
-Do you think the diet the rats were fed is sufficiently proper for a rat to show a meaningful increase in lifespan for IF specifically?
-Part of my skepticism in this was based on the tumors. I have heard it said that primitive cultures who eat a natural/paleo diet don't get cancer. If these rats are getting cancer then is it possible their diets are were poor or would you think that the primitive culture's IF was the reason for the lack of cancer. Or is it possible that the rumors of primitives not getting cancer is overblown?
-It is interesting to see the gender differences. My wife has a MUCH harder time fasting 24 hours or so. For me it is a breeze. Perhaps there is a reason for this? Do you notice this as consistent for women? Would you suggest a different IF protcol for women?

Sorry for so many questions, but this is a really good, thought provoking post. Thanks,


Richard Nikoley said...


Excellent data gathering and analysis.

Not to just produce a gratuitous link, but fasting is one thing I stumbled upon rather early on in my own path and I have done some extreme self-experimentation.

Here's a permalink search to my fasting links:

What I found is that what apparently is autophagy brought on by fasting helped me to build a whle lot of strength even though virtually all of my workouts were after a fast of 24-36 hours.

I got to where (and still do) I could have amazing high resolution into hunger, bringing it on and turning it off at will just by varying intensity.

Since I'm close to goal body comp I know do the extreme fasts only about once every coupla weeks, but I do at least 12-15 hours every day just because I'm not hungry enough to really bother with meal prep.

At first (a coupla years ago) I did not at all understand the reasoning behind an eating window, but I seem to have "evolved" naturally into a daily eating window of 11-12PM to 7-8PM, and nothing in-between, and it's really easy.

Ned Kock said...

Great posting, thanks; a lot of very useful data. I agree with your conclusion.

Among the scariest side effects of CR are the psychological effects, in my opinion. Many people doing forced CR, as in the Biosphere 2 experiment, seem to develop psychosis. Some appear to adapt well to CR and never have this problem though.

A few more advantages of IF over CR: (a) fasting promotes testosterone secretion (in men) together with ketosis, which helps burn fat and build muscle at the same time in those who do resistance training; (b) fasting promotes the secretion of growth hormone, with a number of benefits.

Aaron Blaisdell said...

@Don. Splendid post! I've incorporated IF into my paleo-ish lifestyle with amazing results. It's amazing how easy it is to do when running in ketosis.

@Jeff, regarding your question as to why rates of mammary tumors were so high in the rats, it is probably not due to a lack of any important nutrients in their diet. It's been shown time and again that female rats that do not have an opportunity to breed are at much greater risk of developing mammary tumors compared to rats who have bred at some point in their lifetime. Don't know why this is, but it's likely that the rats in this study were single housed (or at least not housed as breeding pairs). You think rabbits have high baby output? I doubt the scientists wanted 10 or so rat pups on their hand per breeding female once per month throughout the study!

Don said...


This looked like a pretty good rodent diet to me, the only really crap food in it was corn starch. However, it certainly did not have the range of plant matter that a wild rat would ingest, which very likely increased the risk of tumors. Also see Aaron's comment, which applies also to humans. Breeding reduces estrogen exposure which reduces risk of tumor formation. H-G women almost without exception had several children.

I have also found that women have a much harder time adapting to fasting and can't tolerate the duration of fasting. Martin Berkhans (Leangains) also notes the same; he recommends initially a daily 16 hour fast for men but only 14 hours for women.

Women can adapt but more slowly to longer fasts.

I believe this has to do with female hormones. Their hormonal environment (estrogen dominant) increases fat storage leaving less available for burning. This is especially true of women in Western industrialized nations (e.g. U.S.), as studies show they have significantly higher estrogen levels compared to women in non-industrialized cultures and some Asian nations (e.g. Japan).

Eating more cabbage family vegetables will help a woman improve this situation, because these contain DIM and other compounds that help the body remove excess and harmful estrogens.

Yes, I think wild diet + fasting will increase lifespan over ad libitum wild diet. Fasting allows cellular cleansing that would not occur on an ad libitum wild diet.

Aaron Blaisdell said...

Don wrote: "Eating more cabbage family vegetables will help a woman improve this situation, because these contain DIM and other compounds that help the body remove excess and harmful estrogens."

Got a reference to primary literature on this, Don?

Interesting tie in to today's MDA post about BPA in foodstuffs, which is associated with all kinds of harmful xenoestrogenic effects. I wonder if eating cabbage-family vegetables, especially fermented ones like sauerkraut would help rid the body of these as well.

Don said...


Check this article:

Brassica Vegetable Consumption Shifts Estrogen Metabolism in Healthy Postmenopausal Women

and this review:

Cruciferous Vegetables and Human Cancer Risk: Epidemiologic Evidence and Mechanistic Basis

I don't have a reference handy but I believe the xenoestrogens get disposed by the same liver mechanisms that dispose of "bad" estrogen (16-alpha-hyrdroxyestrone), which mechanisms get supported by indoles from crucifers.

zach said...

There is no question many people have great results with IF, but what do you think about the negative studies on Dr. Eades site? I'm concerned because I eat one large meal a day at night, low carb. In the morning I'll usually have a glass of raw milk with a couple raw eggs and eat nothing until night. I was doing this before I went low carb because I just don't get that hungry at "lunch" time. I'll get some pangs late morning or early afternoon but they go away pretty quickly.

Ned Kock said...

I read the article in which Dr. Eades talks about IF and ends with a not-so-positive note. I just don't have the link here, but I have a link to another article by Dr. Eades on IF, which is generally positive. It looks at IF in the context of Ramadan.

If I recall correct, in the not-so-positive article about IF by Dr. Eades, he states that his experience with IF was good, and so was his wife's. The problem seemed to be with many of his patients.

I remember reading that article and wondering whether the patients really followed a true IF regimen. People may say that they are doing IF, but not walk their talk.

Also, and Dr. Eades touched upon that as well, gorging on refined carbs and sugars seems to negate some of the benefits of IF, although not all. Refined carbs and sugars promote fat deposition, while fasting promotes fat burning.

My guess is that an exaggerated consumption of refined carbs and sugars in the hours in which you are not fasting may completely negate the benefits of IF, especially if what one is doing is a half-hearted IF to start with.

Paul A Drockton III said...

Good article. The Every Other Day Diet plan is great if you need to shed some pounds quickly. It is also great if you have been putting off dieting because you are too busy to starve yourself. If you need lots of energy, the Every Other Day Diet gives you that.

Blanche said...

I realize this is a response to an old post, but I wanted to share an observation.

My mom and my aunt (her little sister) are both concentration camp survivors. Mom relates that she weighed about 65 lbs when she was liberated. (She's short, before osteoporosis she was around 4'10".) She was born in 1919, so you can roughly estimate her nutritional deprivation, progressing to near starvation, from late teens to early 20's.

The two of them are the only siblings who went through it, who survived the experience. (Two siblings made it out of Europe early, the rest died.)

The two who survived, one in Israel and one in the US, died - one in 1966, the other in the late 1970's.

Mom and my aunt have outlived everyone. Their health is a touch fragile, but Mom walks her dogs nearly every morning, lives in her own home, goes to Synagogue every Saturday, and for being nearly 91 is frankly in better physical shape than many "healthy" people half her age.

We have some spoken records of longevity in my family, but it's hard to say what our "oldest potential" will be, as the oldest to that point, one of Mom's great uncles and aunts, starved to death in the Warsaw Ghetto in their 90's.

And me? I use the "Warrior Diet" protocol much as I can, stick to a paleo eating regimen much as I can, and at 47 am apparently healthier than a big chunk of my peers and relatives.

Thank you for your studies, you're providing a lot of food for thought in our household.

Don said...


Thanks for that comment. Studies tend to support the idea that food restriction early in life leads to longer lifespan. I wish you, your mother, aunt, and entire family well.

Same for all my readers!

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