Thursday, May 27, 2010

Does Intermittent Fasting Increase Lifespan?

Some say intermittent fasting makes you live longer.
Some say feasting and fasting will keep you younger. (Photo by bowtoo)

I often hear or read that intermittent fasting has all of the same benefits of calorie restriction. The idea is that by not eating every now and then while keeping total calories the same you would enjoy the same health effects as you'd get from simply eating less. Including living longer.

This mantra is repeated even in scientific papers, but is it correct? It's certainly easy to see the appeal: since actual calorie restriction means you're counting every calorie and going hungry for most of the time, intermittent fasting seems like a fantastic choice. Besides, the concept does make sense on the surface. Deprive your body of energy for a while, let autophagy do its work, and live longer. It seems to work for fruit flies and worms, after all, so why not humans?

Because humans are more complex. While simple species like roundworms can be very useful for screening life extension therapies, they are no guarantee that the same therapies work in humans. There are a million ways to extend lifespan in roundworms and fruit flies, but much less in rodents, and even less in humans.

Unfortunately, it looks like intermittent fasting (IF) is one of these cases. For obvious reasons, we don't have lifespan studies on IF in humans, but what we do have is studies on rats and mice. And, despite what the popular belief is, the data is much less promising than one might hope. The rather disappointing conclusion of the studies seems to be that intermittent fasting without caloric restriction does not extend lifespan. When it is accompanied by caloric restriction (CR), it does extend lifespan – and it looks like the degree of life extension is highly dependent on the degree of CR.

The reason you see studies showing increased longevity from IF in the first place is because most rodents eat less when they fast every other day. While humans generally compensate for a fast by eating twice as much the next day, mice and rats generally don't. They do eat more, but not twice as much – which means they are calorie restricted.

Don't believe me? Let's take a look at all the studies on intermittent fasting and longevity in mammals. Note that I've skipped all the alternate-day feeding studies that have not looked at lifespans. There are a lot of papers showing other kinds of health benefits from fasting (some of which are also a result of CR!) , and I'm not saying fasting is not healthy in general, just that it does not seem to extend life.

A critical look at the studies

The first paper I could find on the subject is from 1945 (link), not too long after the positive effect of calorie restriction on lifespan was discovered. This paper briefly mentions an even earlier study from 1934, in which mice fasted for two days in a row each week. The average lifespan of the fasted mice was slightly longer than those of controls, but the difference was not statistically significant. There is no mention of weight and food intake.

In the 1945 study, male and female Wistar rats were put on various versions of intermittent fasting. The rats fasted either one day in four, one day in three, or every other day. Fasting was begun at the age of 42 days and was continued until the rats died.

With the exception of females fasted once every four days, the average lifespans of all fasted rats exceeded that of the controls. The increase in lifespan was slightly greater in males than in females, although females still outlived males in general. In male rats, the most effective method was fasting every other day, while in females fasting once every three days gave the best results on average. However, both the male and female rat that lived the longest (1057 and 1073 days, respectively) were fasted every other day.

Food intake was not measured, but since the intermittently fasted rats weighed less than the control rats, we can assume that they also ate less. No drastic retardation of growth was seen, however. So, the first available study on intermittent fasting shows that when rats are intermittently fasted, they don't compensate for all the missed calories on the ad libitum days, and thus are CR'd, and therefore live longer. No big surprise there.

After this study, there was a gap of four decades before similar experiments were done again. During the 80's and 90's, three papers on intermittent fasting and lifespan were published by the same team. In the first one, male Wistar rats were fed either ad libitum or every other day since weaning (link). The mean lifespan of the fasted rats was 83% greater than that of the control group. And, just like in the 1945 study, fasting resulted in a lower body weight. The abstract doesn't mention the exact weights, but since the fasted rats took 75% longer to become fully grown, it looks like they ended up eating significantly less.

In the second paper, male Wistar rats were again fed ad libitum or every other day since weaning (link). This time they were also allowed voluntary exercise. The fasted rats exercised less in their youth but more when they were older. They also lived longer and weighed less than the control rats. However, in contrast to the first study, their growth duration was the same while growth rate decreased. That is, it looks like in the first study both groups eventually grew to the same size, while in the second study the IF rats remained smaller.

The third paper looked at the longevity effect of intermittent fasting (every other day) on three strains of mice, beginning at various ages (link). In two of the strains, mean and maximum lifespan increased and body weight decreased. The A/J strain, on the other hand, showed different results. When intermittent fasting was begun at 1.5 months, the mice lived longer despite not weighing less. When it was begun at 10 months, they again weighed the same as controls but actually died earlier. The rats that began fasting at 6 months weighed less than controls at some ages but showed no difference in lifespan.

Conclusion

In summary, it looks like intermittent fasting extends lifespan in rats and mice only when it is accompanied by calorie restriction. It does not mean that the animals are also put on CR; rather, they just naturally end up eating less (unlike humans, who tend to be very flexible and good at compensating for calories). And, in the rare cases that the animals actually do eat twice as much the next day, their lifespans are not increased.

For those who are doing IF for other reasons than life extension – such as improving insulin sensitivity or ">weight loss – this is not necessarily a concern. While some of the other health benefits reported in the studies are probably a result of calorie restriction, just like lifespan increases, I suspect IF even without CR still has some benefits in humans. It's just that based on the rodent studies, those benefits won't be enough to make us live longer.

For more information on diet and longevity, see these posts:

Dietary Supplement Increases Lifespan by 11% in Healthy Mice
Slowing Down Aging with Intermittent Protein Restriction
How to Live Forever: My 5 Steps to Immortality
Intermittent Fasting Reduces Mitochondrial Damage and Lymphoma Incidence in Aged Mice



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15 kommenttia:

Anonymous May 27, 2010 at 10:11 PM  

Hi,

I am regular reader of your blog and interested especially in the topic of ADF/IF. For the past 3 months I have been fasting 3 days a week to lose weight, and have lost around 35 pounds. My routine is to fast Mon/Wed/Fri, which leaves four days of normal eating including the weekends, which makes it easier to be with other people then. I stop eating at 10pm on an eat day and don't eat again until after 8am on another eat day.

From all that I have read I think there is a significant difference between IF with eating windows where one eats every day in fact, and ADF where one routinely has 36 hour fasts.

On the HealthyFellow blog he recently interviewed Dr. Krista Varady regarding her studies at the University of Chicago, on both mice and humans. She however now uses a variation of the so-called Johnson Up Day Down Day Diet, where one eats only 20-25% of normal on down days (basically a light lunch), instead of fasting totally on fast days.

But as you note regarding life extension, and also regarding how much weight one loses, a lot depends on whether there is true caloric restriction or one merely compensates almost fully on eating days. Even though I east "lowcarb-ish" on eating days, nuts and cheese as calorie dense foods, can be a low-carber's undoing, as Dr. Michael Eades has noted in the past on his blog. So I have to watch my consumption of almonds esepcially.

Overall for me though it works very well, and I do eat pizza once a week contrary to total low carb. And I think is easier than if I tried to either eat less every day or just every other day even. Although I probably could stuff myself with enough fat and carbs to totally compensate for fast days, it would be hard. So I think ADF, even the 3 day version I do, is better than IF at producing ongoing caloric restriction.

Dr. Varady did say that even for her version she suspects that not more than 10-15% of the public would be able to stick with it, and I imagine she is right. People who eat for emotional reasons and bingers especially will not be able to stick with it I think, but then of course they can't stick with anything.

For me ADF is a real blessing and I wish I had learned of years ago as I was steadily gaining weight year after year. And I think when I finally reach maintenance it will take just 1 day of fasting when eating reasonably on other days to keep from gaining, or two fast days if I splurge like over the holidays. Best of all fussy stuff like counting calories and weighing portions is omitted.

The bottom line to me is that both ADF and low-carb eating are very good individually to lose weight and be healthier. But together they are a slam dunk.

As to life extension, maybe I will be willing to keep up with ADF for that if it seems promising, though I suspect it would take lowering calorie intake on eating days to induce reduced metabolism to make it viable. Or practice IF by eating breakfast and lunch only and skipping dinner.

Sorry for the overly long response :).

MikeF

JLL May 28, 2010 at 8:06 PM  

@MikeF,

Thanks for your comment. Looks like IF is working well for you. I notice you use the term "alternate-day fasting" for 36 hour fasts, which makes sense in humans. In the scientific literature IF and ADF are interchangeable, because the studies are usually done on rodents whose sleep cycles are not like ours. I tried 36 hour fasts for a while too but found them rather difficult -- specifically, going to bed hungry was a challenge. But if you can do it, for autophagy and losing weight it is probably quite effective.

I have actually considered trying the version of IF/ADF where you eat less every other day and compensate the next. I might combine this with low-protein meals on the semi-fast days to maintain autophagy.

- JLL

Delilah May 29, 2010 at 1:05 AM  

I practiced ADF/IF most of last winter (only quit because of marathon training) and I could go on forever about how much I liked doing it and how great I felt, but mostly what I want to chime in is that I was never able to compensate for the calories (hence me not doing it anymore because of the marathon training). I was probably somewhere between 2000-3000 calories on the days I was eating, I simply could not eat any more while still eating healthy (or mostly healthy). It is interesting that you posted this because many of the perks I felt (and saw) probably had more to do with the CR, but the way I was able to comfortably practice CR was with ADF/IF as a tool. I had been attributing all of the benefits to the ADF/IF but I think I'll phrase it a little differently now. Thanks. Fascinating.

Anonymous May 29, 2010 at 4:29 AM  

JLL,

36 hour fasts do make for some long days, although you know you will be eating the next day. One problem some people have including myself occasionally, is insomnia. Which is the opposite situation from eating lots of carbs.

I realize from reading your other stuff that you are trying to restrict protein. That is very difficult with ADF since one needs to get a lot of protein on eating days to limit muscle loss. But your suggestion of using the JUDDD version of IF and eating non-protein on the down days seems good, especially if it were mainly leafy greens and such.

MikeF

The Cave Man May 29, 2010 at 7:34 AM  

JLL,

Help me resolve an issue I am having when thinking about this stuff:

The average life expectancy for US male is 75.6.

To me it feels like if we follow many of these marvellous lifestyle guidelines you and many people on the Internet are investigating, like a paleo style diet and IF and supplementation and a thought to AGEs/ALEs, and the dozens of other small but important things, it feels like we have a really good chance of making it way past 75.6!I have grandparents who never did any of this stuff who made it into their 90's, and just think how much better modern medicine will be (even with the most pessimistic projections) that 100 doesn't sound all too unachievable!

So I guess my question is, don't we have to look a little past the data on this, and sort of not get caught up on the strict lifespan extension figure and appreciate that some form of IF incorporated into your lifestyle over decades will slow down your rate of aging? There are so many different physiological effects from IF, and beneficial things happening... Or is it just 'well the data doesn't say that' and we just have to follow the science we have? ... Help me out :)

Mitch Fletcher May 31, 2010 at 3:26 AM  

You make a good case, and I have to agree with you that it would seem there is no evidence that IF without CR can extend lifespan.

Are these rodents for sure calorie-restricted? Or could they lose weight based on metabolic changes brought about through the IF, i.e they simply shift to a leaner 'set-point'. Bit of a stretch.

I'm happy to continue with IF for now, given that I feel good, and it improves markers consistent with good health. If I experience some CR, then all the better.

There do appear to be some differences independent of calories. I think I've read that BDNF levels increase with IF but not CR, but then again these studies may involve CR as part of IF.

webster May 31, 2010 at 5:19 AM  

JLL I think you should take a look at this study

http://www.ncbi.nlm.nih.gov/pubmed/17908557

on glucose restriction (not methionine this time), extending life span. And it also questions whether antioxidant supplements are disruptive to protective "mitohormesis".

JLL June 1, 2010 at 7:02 PM  

@The Cave Man,

You are correct that from the perspective of the individual, anything that helps you live longer than you otherwise would does count as a kind of life extension; e.g. avoiding unhealthy foods to reduce cancer risk, diabetes and cardiovascular disease. If the average age is 75.6 years and you live 85.6 years because of a healthy lifestyle, isn't the 10 year difference all that matters?

I would say yes and no. To live to 80 or 90 or even 100 really only requires avoiding the most common diseases. It does not require slowing down the actual aging process. This kind of disease avoidance is often referred to as "squaring the curve" -- which statistically means bringing mean lifespans as close to maximum lifespans as possible.

For humans, the maximum seems to be something like 120 years. For those without lucky genes, the maximum may be closer to 100. You can make it to this maximum by avoiding diseases without slowing down aging (aging is a multifactorial process) per se, but to make it past the maximum, aging itself would have to be slowed down. Not getting cancer is not really slowing down aging, it's squaring the curve. It's pushing the maximum that is often referred to as life extension. Caloric restriction is one of the few things that actually pushes this maximum in animals. The hypothesis, then, is that a healthy lifestyle (let's say IF + paleo) could make you live to 90-110, but CR could make you live to 110-130.

Which things actually measure the speed of the aging process is up for debate, of course.

- JLL

JLL June 1, 2010 at 7:10 PM  

@Mitch Fletcher,

We can't say for sure whether the animals are calorie-restricted, because food intake was not measured. I don't find the idea of a leaner set-point impossible, but I would say that the rodents eating less is the more probable explanation.

But, since the A/J mice on EOD feeding since 1.5 months of age lived longer despite not losing weight and those on EOD since 10 months died earlier despite not losing weight, it looks like there is something else besides CR going on as well. Also, according to the full paper of that study the drop in weight does not go completely hand in hand with the lifespan -- that is, the mice that weigh the least do not always live the longest.

- JLL

JLL June 1, 2010 at 7:13 PM  

@webster,

That study is on C. elegans; we know hormesis works pretty well for C. elegans, but does it work for mammals? If there is a study where rats or mice live longer when glucose is restricted but total energy intake is kept the same, then I haven't seen it.

- JLL

Blind Spectator June 18, 2010 at 9:56 PM  

JLL,

I just discovered your blog and spent a few hours reading older posts - and I love it! Keep up the great work.

My question is somewhat naive: if longevity is important for you, and if you believe that CR is likely to have additional benefits over IF for longevity, why do you practice IF but not CR?

Thanks,
Blind Spectator

Dr. William Davis June 28, 2010 at 7:43 PM  

Thank you for a brilliant review of the data!

Your conclusion makes perfect sense.

JLL July 17, 2010 at 2:42 PM  

@Blind Spectator,

Sorry for the late reply, I missed this comment somehow.

The reason I'm not doing CR is because I think the negatives outweight the positives. Humans cannot do such severe CR as animals, and the potential lifespan gain will therefore be relatively small -- less than ten years.

CR does improve healthspan, which will increase your chances of making it to longevity escape velocity, but there are other ways of improving healthspan. I don't want to calculate my energy intake every day and to measure everything, and I don't want to get any skinnier than I am.

- JLL

Howard Roark April 6, 2011 at 9:16 AM  

Hi, I just found your blog today and have been reading through it. I see your post on how you say IF isn't valid since the rats were fed less amounts. That strikes me as really unusual, since it would be so easy to control for and would obviously invalidate the study.

I did a Google search and turned up a study where they were fed the same as normal with fasting and it showed lots of benefits:

http://www.pnas.org/content/100/10/6216.full

JonnyU December 23, 2015 at 8:47 PM  

Hi JLL - I discovered your blog today and it's really fascinating! Sorry to see you aren't updating it more, though I'm sure it was quite time consuming.

I'm 6'5'', 168lbs (ie, pretty thin). I struggle with acne and eczema, which I've managed to cope with my following the a lacks version of the Autoimmune Paleo diet. I still eat grains, legumes and tofu, as my girlfriend is vegan and we live together - however it's challenging for me to put on weight without incurring autoimmune side effects or feeling like my digestion is moving well.

Recently I learned the my fasting glucose levels are high, and I must assume it's due to my carb consumption. I intend to try IF; really hoping I'm not going to drop weight.

Curious, are you still doing IF? Would love to hear an update on what you've learned lately!

All the best,
Jon

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