Antioxidants and Intermittent Fasting – Good For Longevity?

Are blueberry antioxidants beneficial for intermittent fasting? (Photo by Simply Bike)

Is it possible to live longer by combining the benefits of intermittent fasting (IF) and plant polyphenols? A new paper claims that taking polyphenol antioxidants during dietary restriction increases the lifespan of mice more than dietary restriction alone. The antioxidants used in the study were blueberry, pomegranate and green tea extracts.

The subject of the paper – "Potentiation of dietary restriction-induced lifespan extension by polyphenols" – is certainly enough grab the attention of anyone interested in life extension. The abstract seems promising too (link). Here's a quote:

Dietary restriction (DR) extends lifespan across multiple species including mouse. Antioxidant plant extracts rich in polyphenols have also been shown to increase lifespan. We hypothesized that polyphenols might potentiate DR-induced lifespan extension. [––] Polyphenol compounds may potentiate IF-induced longevity by minimizing specific components of IF-induced cell stress.

Let's look at these claims in more detail. First off, it's not clear from the abstract what exactly the authors mean by "dietary restriction". The full paper, however, reveals that they use the term to describe pretty much any kind of diet where access to food is limited, including traditional calorie restriction and intermittent fasting.

The longevity confusion

The problem with that opening sentence is that dietary restriction extends lifespan across multiple species only when it equals calorie restriction. That is, you can make a mouse live longer by only feeding every other day, as long as it results in less calories consumed. This is an important distinction, because many people – including longevity scientists – keep propagating the myth that intermittent fasting has the same benefits as calorie restriction. It doesn't. The reason that IF prolongs lifespan in some species is because the animals fail to compensate for the missed calories on their feeding days.

The next sentence is just as problematic. Yes, plant antioxidants have been shown to increase lifespan, but the question is, compared to what? So far, no one has succeeded in exceeding the known maximum lifespan of mice by feeding them antioxidants. Instead, what we see in many studies is that the antioxidant group lives longer than the control group.

The problem is that almost always, neither group lives very long. Poor diets, poor animal husbandry, poor environment – all play a role in how long the animals live. So, in essence, the antioxidants merely make the unhealthy mice a bit healthier. But this is like making a human live 70 years instead of 60 years by giving them some veggies with his daily bread and then claiming that "vegetables extend human lifespan".

Comparing lifespans

That said, there are some interesting figures in the full paper. The graph below shows the survival rates of the three groups; one fed the control diet, the second fed the same diet but only every other day, and the third fed a diet supplemented with polyphenols every other day:

There's a big drop in the survival rate of the control group around 22 months. For the IF groups, the survival curves look a lot better. So how does this compare to the average lifespan of similar mice kept in good laboratory conditions? Here's a graph of age ranges and survivorship of C57BL7/6J mice (the same strain used in this study):

This survival curve is based on a cohort of 150 male and 150 female mice. As you can see, at 28 months half of the mice are still alive. That's about 850 days, which is a pretty normal figure for mean lifespan of this strain of mice in the literature.

Once again, in the antioxidant study the control group dies earlier than is normal. For some reason, half of the mice are dead at 22 months instead of 28 months. One possible reason is the use of a high-fat diet to "mimic the effects of a Western diet", as the authors put it. This seems like a strange idea to me, because a typical Western diet is no more a high-fat diet than it is a high-carbohydrate diet. Furthermore, plenty of humans (myself included) seem to do quite well on a high-fat diet, whereas with mice it's somewhat different.

The survival curve of the IF mice in the first graph is slightly better than that of the normal-fed mice in the second graph. But that is hardly a surprise, given that both the IF group and the IF + antioxidant group had lower body weights than the control group. In other words, the intermittent fasting once again made the mice eat less than the control group, which in turn resulted in a slightly longer lifespan. It's good to keep in mind, however, that with just 10% calorie restriction longer lifespans have been reported in other studies, so the result is not too impressive.

Conclusion

Perhaps the most interesting result is that the IF + antioxidant group lived slightly longer than the IF group. There's no concensus as to whether it's a good idea to combine CR or IF with antioxidants. It may be that plant polyphenols are essential for optimal nutrition and good for activating sirtuins (which play at least some role in longevity), but there is also some evidence suggests that taking antioxidants may interfere with hormesis and thus diminish the effects of CR.

In this study, the antioxidants had a beneficial effect. While the IF diet by itself activated pro-inflammatory pathways, adding plant polyphenols to the diet blocked this effect. The authors identified 20 gene sets that were down-regulated by the addition of polyphenols, most of them related to immune response, inflammation, cell differentation and tumorigenesis. 

This suggests that if you're doing intermittent fasting, adding some blueberries, pomegranates and green tea to your diet may not be such a bad idea. Note, however, than the mice did not have access to polyphenols during their fasting days, so this study tells us nothing about taking antioxidants during fasting. It also doesn't say much about how polyphenols affect regular calorie restriction without IF in humans.

For more information on intermittent fasting and longevity, see these posts:

Lithium in Drinking Water May Lead to Longer Life
Does Intermittent Fasting Increase Lifespan?
Alternate-Day Feeding and Weight Loss: Is It the Calories Or the Fasting?
Slowing Down Aging with Intermittent Protein Restriction

Read More......

Nootropics, Longevity and More: The Year 2010 in Review

Comments or suggestions for the year 2011? Drop a comment! (Photo by Altus)

Happy New Year everyone! I hope your holidays went well and you're ready to make 2011 even better than last year. But before we do that, let's take a look at some of the best bits and pieces from 2010.

In January, I finally got a chance to see Aubrey de Grey for the first time. His presentation in Helsinki, Finland was mostly familiar to me already, but I enjoyed it nonetheless. Perhaps the most interesting part was when the audience got to ask questions; I thought Aubrey's answers were good, especially given that some of the comments were pretty frustrating (apparently some people think going through their entire family history somehow qualifies as a question). If you want to check out the presentation, the video is still available online through the link above. And in case you want to know more about Aubrey himself, he was also interviewed in Wired.com a while ago.

Nootropics are gaining more and more attention these days. Even 60 minutes ran a segment on students boosting brain power to do better in their studies. Amphetamine derivatives are still the most popular choice – but whoever comes up with an "organic herbal formula" that actually works as well as Adderrall is going to be rich. I also did an experiment with Ashwagandha to see whether it had a nootropic effect. It didn't, at least not the brand I was using.

And then there was the experiment with BioSil, the stuff that is supposed to make your hair and nails stronger. The science seems solid, but as I wrote in my conclusion, the price of the liquid supplement doesn't seem worth it, since orthosilicic acid, the active ingredient, is also present in my favourite beverage.

Speaking of hair, a lot of people have asked for an update on the soy isoflavones + capsaicin experiment, another one of my attempts at finding a magical hair growth formula that will make me filthy rich. The experiment has been going on for six months now, which is longer than the five months that the original study lasted, so perhaps a proper update is indeed due. So far I haven't seen much visible changes, however. I'm now adding various kinds of chili powders and pastes to almost all my foods, but I'm thinking of ordering capsaicin supplements to be sure I'm getting enough to match the study. And I also need another bottle of soy isoflavones.

I've tried a lot of useless supplements and topicals, but last year I came across something that really, actually works: retinoids. I've now been using them for over a year and I can really see the difference. My advice to anyone looking for real results is to forget about all the overpriced skin creams that are really nothing but moisturizers and go for tretinoin instead. Of course, since it actually works it's prescription stuff, so you can't just buy it from the store, you'll have to order it online and hope your package doesn't get confiscated by the customs officers who surely know better what you need than you do. Thank god for regulations!

Probably the longest and most throrough post of last year was about human hibernation and how it might relate to longevity. In addition to a look at the current state of hibernation science, there's also the odd legend of lotska, the art of hibernation allegedly practiced by poor Russian peasants:

At the first fall of snow the whole family gathers round the stove, lies down, ceases to wrestle with the problems of human existence, and quietly goes to sleep. Once a day every one wakes up to eat a piece of hard bread, of which an amount sufficient to last six months has providently been baked in the previous autumn. When the bread has been washed down with a draught of water, everyone goes to sleep again. The members of the family take it in turn to watch and keep the fire alight.

And of course, no post on slowing down metabolism would be complete without Indian fakirs and frozen mountain climbers. Check it out if you have the time, it's fascinating stuff.

While the Russian peasants may have spent most of their winter sleeping to avoid starving, there are also those who can eat as much as they like and still avoid getting fat. Even without any exercise. I'll let other bloggers fight it out over the details of the energy equation and whether a calorie truly is a calorie, but take a look at the BBC documentary in the link to see what I mean. Also check out the comment section, some interesting anecdotes in there.

How is the life extension movement doing these days? Well, the same old (and false) arguments against longer lifespans are still there, but the overall mood is pretty optimistic. Personally, I've noticed that younger people tend to be more open to the possibility of life extension than middle-aged people. Go figure. Meanwhile, the Russians have apparently found the cure for aging, although I haven't heard anything new on SkQ1 since September. But that's okay, because the next fountain of youth is already here.

Long-time readers of this blog probably remember that I did intermittent fasting for over a year. Part of the reason was that I wanted to see if 24-hour fasts could be done – I wanted to be the master of my hunger, so to speak. However, the most important reason were the studies showing positive effects from intermittent fasting without restricting total calories. You know, the whole "cleaning cells from junk through autophagy" thing.

But alas, after going through the studies more carefully, I was disappointed to find out that whenever intermittent fasting increased lifespan in mice, total calories had also been restricted. In effect, intermittent fasting extends lifespan only in conjuction with caloric restriction. Some of the other benefits of fasting may still be valid, to a degree at least, but without potential gains in lifespan, I don't see the point in doing a strict 24/24-hour cycle of fasting and feasting anymore. Besides, I now think that even full-blown calorie restriction would only give me a few extra years. Why? Because humans just can't do CR the same way rodents can. More on this later. Meanwhile, see my updated health regimen.

Of course, there were also several other posts which I didn't mention here; see the archives section in case you missed them. And just so you don't miss anything interesting in the future, remember to subscribe to my feed and to follow me on Twitter, which I use to post stuff (life extension, health, science) I don't have time to blog about in depth. Oh yeah, and tell your friends to do so too!

For summaries of previous years, see these posts:

10 Human Experiments of 2009 – Year in Review
7 Human Experiments of 2008 – Year in Review

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Does Intermittent Fasting Increase Lifespan?

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

Read More......

My Current Health Regimen v2.0

One of the changes has been an increased intake of fruit and vegetables. (Photo by YimHafiz)

This is my updated health regimen, aimed at adding a significant number of healthy years to my expected lifespan. As it's subject to change, I will keep this post updated accordingly. Major revisions (such as v2.0) will appear once a year or so; minor changes (such as v2.1) will be made as needed. With every major revision, I will move the post from the archives to the front page.

Since a long, healthy life is preferable to a short life by most people, following the regimen would make sense even without considering technological innovations. The true goal of my regimen, however, is to stay alive long enough to see rejuvenation therapies become a reality. In the long run, each year that I'm able to add to my expected lifespan now through things like dietary changes, exercise, and supplements, may grant me several extra years in the future.

Therefore, even those lifestyle changes that require considerable effort and resources while offering a seemingly limited benefit, make sense if one looks at the big picture. For a chance to see the world in 2090, I'm willing to skip the cheeseburger today.

My health regimen consists of four categories: diet, supplements, physical exercise, and brain health. All of the items under each category have some kind of scientific basis, and in contrast to my ongoing experiments, will remain a part of the regimen for the time being. Therefore, my current experiments are not a part of my long-term health regimen – unless they prove to be beneficial, in which case they'll be moved from ongoing experiments to the regimen.

Main changes from v1.0: none.

Avoiding harmful foods

The most important part of my diet is avoiding unhealthy things; increasing the intake of healthy things only comes in second. This is because preventing damage from happening in the first place is easier than repairing it later on.

I consider the worst culprit of modern diets to be an emphasis on grain products, fructose, and polyunsaturated fatty acids. There's considerable evidence to suggest that most people would do much better without them. Hence, things like pasta, rice, bread, candy, fruit juices, and most vegetable oils are off the daily menu. I only eat them rarely, and then simply because they taste good. For the past few months, I've allowed myself to eat whatever I want once a week (usually foods like pizza or fresh bread), which seems to be working well.

I originally cut back on my fruit intake, which used to be quite high some years ago, because I learned that fructose increases triglycerides especially in men, and fructose is not handled very well by the body in general. I later learned that fructose also forms AGEs much more rapidly than glucose, which kept me from reintroducing most fruits to my diet and eat berries instead, since they contain more nutrients per fructose calorie. However, I've now increased even my fruit intake a little, having read more about the AGE-inhibiting effects of phytonutrients found in fruit. I will expand on this later, but for an example of what I'm talking about, see my post about carotenoids inhibiting lipid peroxidation.

While much of this fits well with paleo dieting, I also diverge from the paleo diet these days. You may or may not remember that I used to be a potato hater back in the day, both because they could not be eaten raw (making them anti-paleolithic) and because of their high carb content. Basically, potatoes are just empty calories. But once you have your insulin sensitivity and blood glucose under control, I don't think a few potatoes now and then is much of a concern. At least they're low in fructose.

As you may recall, I followed a low-carb diet for the past year with an emphasis on paleo foods. I got on the low-carb, high-fat wagon in the first place to prove that eating a diet high in fat does not make you fat – and it didn't. However, this diet combined with my year-long intermittent fasting experiment resulted in a moderate-to-high intake of protein, the longevity effect of which I'm now questioning. To lower my protein intake slightly means eating either more fat or more carbohydrates, and since my fat intake is already very high, I've reintroduced some carbs into my diet. That is, I now occasionally eat potatoes not because I think they are necessary for health, but because they are low in protein. More on protein and longevity in future posts.

I still don't make nuts a dietary staple, because of their poor omega-3/omega-6 ratio and because I like to keep my PUFA intake low. That is, I aim not only for a good ratio of omega-3 and omega-6 fatty acids, I try not to eat too much of them in general. Omega-3 is particularly prone to undergo lipid peroxidation, and while nuts probably have micronutrients that protect them from oxidation to some degree, I'm playing it safe until I learn more.

Main changes from v1.0: slightly increased carb intake, slightly decreased protein intake, slightly decreased polyunsaturated fatty acid intake.

Eating healthy foods

Despite eating some more carbs these days, my diet is still fairly low in carbohydrates. My daily intake used to be around 100 grams; I have not measured my current intake, but I suspect it's around 100-150 grams these days. My main protein sources used to be meat, fish and eggs, but during the past year I've cut back on eating eggs because of their high methionine content. I'm still figuring out whether methionine restriction makes sense in humans, but in the meantime I limit my egg intake to 3-4 eggs a week.

Sources of fat, in the order of importance, are olive oil, palm oil, butter, cocoa butter, coconut milk, ghee, coconut oil, and sesame oil. Olive oil tops the list because I love the taste and because it's high in MUFAs but low in PUFAs and consistently does well in just about every health study. There may not be anything magical about MUFAs per se, but even if it's the polyphenols in olive oil that are behind all the positive health effects, olive oil still seems like a good choice. Palm oil is there because it's rich in tocotrienols (at least compared to other natural foods), low in PUFAs and high in SAs (making it suitable for heating), and because I've grown to like the taste.

Lard is off the menu for now because I ran out. Heavy cream has been replaced by coconut milk, partly because of dairy products increasing IGF-1, which may be bad for longevity (more on that in future posts). I don't eat cocoa butter raw (although I could, it's delicious), but I get plenty from all the dark chocolate I eat. Somebody asked me in the comment section why I eat sesame oil since it contains quite a bit of PUFAs, and noticing this was indeed so, I was going to remove it from my diet altogether. However, doing some reading I found that sesame oil seems to reduce markers of lipid peroxidation, so I kept it on the menu. I just use it for taste, however, so my intake of sesame oil is very low anyway.

Depending on my daily menu, anywhere between 50 to 70% of my total calorie intake is from fat. My daily menu has changed a bit, but percentage of fat is still the same. Most of this is saturated fat, which has been given a bad rep for reasons I believe are incorrect. I began reducing grain products and increasing my saturated fat intake years ago, and it hasn't killed me yet. In fact, my HDL has increased and my LDL has decreased on this diet. Triglycerides are not bad but could be better – a testament to my main vices, beer and wine.

There is one cereal grain I regularly eat, however: rolled oats. They're a convenient source of beta-glucan, which appears to be good for cholesterol and avoiding heart disease, and they don't contain gluten. Oats also contain quite a bit of quality protein. I used to eat them with milk and berries, but then switched to a combination of heavy cream and water to reduce my consumption of lactose and galactose (which easily form advanced glycation endproducts, AGEs). Now, I've stopped adding even heavy cream, because milk protein seems to interfact with the polyphenols in berries. So it's a mixture of coconut milk and water nowadays – not as good as cold milk, but still pretty good.

As for red meat, despite how it's portrayed in the media these days, I'm not convinced that meat consumption is harmful. Indeed, a recent review supports the hypothesis that processed meat, not meat in itself, may be harmful. The biggest problem I used to see with meat is the generation of AGEs. Though there is disagreement just how harmful consuming AGEs with food are, I tried to minimize the potential damage by avoiding overcooking and taking supplements. I no longer think AGEs in meat are a huge problem, however – more on this later. The reason I don't eat huge portions of meat like I used to is because of the high protein content.

And finally, the beverage department. I still love my daily coffee, which I drink 1-2 cups per day. Coffee has some nice health benefits too. Green tea is obviously staying on the menu; the studies showing positive health effects just keep on piling up. All in all, beer doesn't really belong to the "eating healthy foods" category, but even beer does contain some good stuff.

As you may recall, I used to drink yerba mate with meals to reduce the formation of AGEs. It's since come to my attention that yerba mate is carcinogenic at higher doses, so I now drink it only rarely. Green tea or black tea are safer bets, despite somewhat contradictory results in reducing AGEs and ALEs.

Main changes from v1.0: decreased egg intake, changes in the use of fats and oils, reduced yerba mate consumption, avoidance of lipid peroxidation.

A note on diet tweaking

It's much easier to point out things that are wrong in various foods than it is to prove something is healthy. These days, I'm more wary of advertising my diet as the best choice for everyone than I was before. Part of the reason is that the more I read and learn about nutrition, the more complicated everything becomes.

Case in point: I used to tell people vegetables are bad because, as an evolutionary strategy, they produce toxins to protect them from being eaten (which is true). Now, having learned of the importance of hormesis, I think vegetables are good because of those same toxins! I was also a huge fan of eating fruit (especially organic fruit) at one point, because it seemed to make sense from an evolutionary point of view. The, I got a little skeptical towards them because of their fructose content. Now, I think the benefits may outweigh the negatives.

All this, however, doesn't stop me from wanting to find the optimal diet for longevity. On the contrary, it's a healthy reminder not to get too emotionally attached to my health regimen, and to be ready to admit mistakes and make alterations as I learn more.

Going without food

The third key component of my diet used to be intermittent fasting. I stated in the first version of this post that "I may change my mind in the future, but for now I expect periodic food deprivation to remain in the regimen." That is still true to some degree: I no longer do a 24/24 hour cycle of fasting and eating, but I don't make it a point to eat three meals with snacks a day either. I often skip breakfast and lunch and eat only dinner.

The thing that lured me to try intermittent fasting was that there are studies suggesting that all or most of the benefits of chronic calorie reduction can be had by alternating zero calories with double the normal calories every 24 hours. While I no longer believe that IF is equivalent to CR, I do think that fasting in general is beneficial. An improved insulin sensitivity is a known result of intermittent fasting. Insulin sensitivity is associated with longevity, and among supercentenarians, insulin sensitivity is common.

Perhaps a more interesting thing about fasting is that it increases autophagy, a process in which the cell consumes a part of itself for energy. This can happen during ordinary cell maintenance, or when the body is deprived of nutrients. Since improved autophagy is at least in part why caloric restriction works, this makes other, less demanding forms of nutrient deprivation attractive options.

The reason I stopped doing strict IF is because I don't think there is much evidence that fasting for 24 hours and then eating for 24 hours is somehow optimal in itself. Most importantly, IF does not extend lifespan in most studies. Why IF is not equivalent to CR is not clear, but recent studies suggest protein may have a lot to do with it. My intermittent fasting diet resulted in huge meals with lots of protein, and I now suspect that this may have diminished much of the potential benefits.

Main changes from v1.0: no more 24/24 intermittent fasting, no more huge protein-heavy meals.

Supplements

The most important supplement in my regimen is vitamin D3. Most people are deficient in vitamin D, and the health benefits are so overwhelming that if there's one supplement I would recommend spending money on, it's vitamin D3. I usually take 5,000 IU of vitamin D3 daily, and at last check, my levels were at 45 ng/mL, which is in the optimal range. Now that it's summer, I'm taking 2,500 IU daily. I know some people take the same amount all year round, but since I do spend some time in the sun, I don't want to overdo it.

One of the supplements that has remained in the regimen since last time is vitamin K2, which is sort of a newcomer in the supplement scene but nonetheless has some impressive studies behind it. I'll write more about it in the future, but here's one study of interest for men: dietary vitamin K2 may reduce prostate cancer. Since fermented dairy products, which I'm not sure are the best choice for health otherwise, are the best dietary source of vitamin K2, I'm taking supplements instead. At the moment, I take 90 mcg of MK-7 (Jarrow MK-7) and 5 mg of MK-4 (Carlson Labs Vitamin K2) every third day in an attempt to find a balance between affordability and the long serum half-life of vitamin K2.

I used to take a tablespoon of fish liver oil daily, because it has lots of omega-3 fatty acids in bioavailable form (EPA and DHA) and almost no omega-6 fatty acids. A higher dietary ratio of omega-3 to omega-6 seems to be very beneficial in general, and fish oil has been shown to decrease inflammation. A commonly quoted optimal ratio is between 1:1 and 1:4, which seems to be close to how our paleolithic ancestors ate. As part of my plan to avoid excess PUFAs, I've dropped fish liver oil from the menu. I'm currently in the process of weighing the pros and the cons; it may be that a tablespoon per day will prove to be worth it in the end.

I also used to take resveratrol with quercetin during fasts to increase autophagy. I would still continue to take them, but unfortunately I can't afford all the supplements I might like to take (including AOR Ortho-Core, which is off the list for the time being), so I take resveratrol only occasionally. Meanwhile, I'm on the lookout for other things that increase autophagy. Curcumin is a cheap alternative, and it has other health benefits too, which is why I add turmeric to most of my foods.

Since my damn blender keeps leaking from the bottom, I'm no longer making smoothies every day like I used to. So these days I just add some ground flax seeds to my rolled oats for the flax lignans. Flax lignans may prevent hair loss, among other health benefits. Some people prefer to take them in supplement form, but flaxmeal is a cheaper and equally effective way to consume flax lignans. For best effects, they should be consumed twice a day with ~12 hours in between. Other things I do to prevent hair loss is use shampoos with ketoconazole and piroctone olamine.

Main changes from v1.0: no more fish liver oil, some supplement cutbacks due to costs, increased curcumin intake.

Exercise

My exercise routine is probably the weakest part of my regimen, compared to how much effort I put into diet and supplements. In the summer, I run for 30-45 minutes once a week to get some aerobic exercise (I should start again, since summer is here!) The goal is to keep the heart and lungs healthy, reduce blood pressure, and improve mood. In the winter, when it gets too cold for running outside, I go to the gym for strength training instead. Strength training reduces the risk of injury, prevents osteoporosis, supports joint health, and prevents muscle loss resulting from aging.

I also practice martial arts, which combines aerobic and strength training, to a degree. The main reason for me, however, is that it provides me with a basic set of self-defense skills and improves coordination. With aging, there is usually an increased fear of falling and hurting oneself – something children naturally don't have. Getting thrown around every week is a way to maintain a healthier attitude towards my body and prevent an irrational fear of getting hurt. I want my mind to rule over my body, not the other way around.

Main changes from v1.0: none.

Brain training

Any anti-aging regime should also take into account the importance of maintaining mental health. It doesn't take a genius to see that people who use their brains actively retain their cognitive abilities far longer than those who are passive.

One of the ways I keep the rational side of my brain fit is reading scientific papers and writing about them on this blog. I like logical problems in general, and I think practicing problem-solving skills are important for everyone, whether it's through work or hobbies. To train the creative side, I do things like play instruments, compose music, and read and write fiction.

My biggest problem is and always has been rather poor short-term memory. I don't know whether it's because my mind is always occupied with a zillion things, but it's more than once that I've gone to the grocery store to buy something I need and come back with something else entirely. This kind of absent-mindedness seems to run in the family. I believe it can be improved through training, however. The memory game experiment intends to increase IQ, but it improves short-term memory as well (I've pretty much forgotten about this experiment lately, by the way – I'll have to start playing again!)

Main changes from v1.0: none.

Quick summary of the health regimen

As a part of my diet, I regularly eat the following foods:

- Meat, fish
- Olive oil, palm oil
- Butter
- Vegetables, berries, fruit, oats, dark chocolate, coconut milk
- Coffee, tea, wine, beer

I limit or avoid eating the following foods:

- Grain products like pasta, bread, and rice
- Fruit juices, candy
- Vegetable oils high in PUFAs

In general, my diet is high in fat and lowish in carbohydrates. I consume saturated fat and monounsaturated fat liberally but limit polyunsaturated fats.

My supplement regime consists of the following:

- Vitamin D3: 2,500-5,000 IU daily
- Vitamin K2: 90 mcg of MK-7 and 5 mg of MK-4 every third day
- Varying amounts of green tea daily
- Flax lignans: 1-2 tablespoons of ground flax seeds daily

My physical health regime consists of martial arts, running (in the summer), and strength training (in the winter). For mental health, I do things that train the creative and logical sides of the brain.

For more information on anti-aging methods and living longer, see these posts:

Anti-Aging in the Media: New York Times on Caloric Restriction and Resveratrol
How to Live Forever: My 5 Steps to Immortality
L-Carnitine, Acetyl-L-Carnitine and Cognitive Function in Humans
Caloric Restriction Improves Memory in the Elderly

Read More......

The Curious Case of Human Hibernation

The survival stories of mountain climbers may be a clue to suspended animation. (Photo by Tim)

Hibernation is a state characterized by inactivity, slower metabolism and lower body temperature. Hibernating animals most often do so to survive food scarcity, especially during the winter. Man is not considered a hibernating animal, but a glance at modern science and strange accounts from the past suggest we may have to revise our views in the future.

James Braid, the father of hypnotherapy and a man with a fascination for the occult, recorded several odd cases of humans surviving hibernation-like conditions in his 1850 book Observations on Trance (link). In his most famous account an Indian fakir was buried alive in the presence of Sir Claude Wade, the English governor at the time. After remaining in the ground for several months, the fakir was reportedly exhumed and restored to consciousness in good health.

No one knows if Braid and Wade were telling the truth, but findings of the same nature have been reported even quite recently. A 1998 paper from Physiology describes two Indian yogis performing similar stunts, although the durations were much shorter (link):

One yogi went into a state of deep bodily rest and lowered metabolism and was able to remain in an airtight box with no ill effects and no sign of tachycardia or hyperpnea for 10 h.

In a different study done in a more naturalistic setting on a different adept, Yogi Satyamurti (70 yr of age) remained confined in a small underground pit, sealed from the top, for 8 days. He was physically restricted by recording wires, during which time electrocardiogram results showed his heart rate to be below the measurable sensitivity of the recording instruments.

A hundred and ten years ago the British Medical Journal ran a short article titled Human Hibernation (link). The article, reprinted in 2000, is a peculiar account of how poor Russian peasants allegedly survive famine by sleeping for half of the year. I'm quoting the full article here:

A Practice closely akin to hibernation is said to be general among Russian peasants in the Pskov Government, where food is scanty to a degree almost equivalent to chronic famine. Not having provisions enough to carry them through the whole year, they adopt the economical expedient of spending one half of it in sleep. This custom has existed among them from time immemorial.

At the first fall of snow the whole family gathers round the stove, lies down, ceases to wrestle with the problems of human existence, and quietly goes to sleep. Once a day every one wakes up to eat a piece of hard bread, of which an amount sufficient to last six months has providently been baked in the previous autumn. When the bread has been washed down with a draught of water, everyone goes to sleep again. The members of the family take it in turn to watch and keep the fire alight.

After six months of this reposeful existence the family wakes up, shakes itself, goes out to see if the grass is growing, and by-and-by sets to work at summer tasks. The country remains comparatively lively till the following winter, when again all signs of life disappear and all is silent, except we presume for the snores of the sleepers.

This winter sleep is called 'lotska'. These simple folk evidently come within '0 fortunatos nimium sua si bona norint!'

In addition to the economic advantages of hibernation, the mere thought of a sleep which knits up the ravelled sleeve of care for half a year on end is calculated to fill our harassed souls with envy. We, doomed to dwell here where men sit and hear each other groan, can scarce imagine what it must be for six whole months out of the twelve to be in the state of Nirvana longed for by Eastern sages, free from the stress of life, from the need to labour, from the multitudinous burdens, anxieties, and vexations of existence.

Don't you just love the poetic style of scientific writing back in those days? The lotska sounds more like an urban legend than an accurate description of lowered metabolism, but in 1906 – six years after the original article appeared – The New York Times ran a story on starving peasants in Russia "lying motionless for days at a time, in order to weaken the pangs of hunger". A few days later, there was a letter to the editor with the following comment on the story (link):

This exigency may be akin to the pseudo-hibernation habitually practiced by Russian peasants in the northern provinces, notably in the Pskov district. If such is the case, the hardships endured by the peasants this Winter may not be as great as the casual reader might be led to believe.

True, the pseudo-hibernation which is general in Pskov has resulted from the fact that famine is well-nigh chronic there; but by pratice from time immemorial the peasants have become accustomed to imitate the habit of the bear and the marmto in Winter, until now the custom is regarded by them as one of the normal conditions of human existence. They have a name for this Winter sleep. It is called "lotska".

In the brief Autumn the housewives prepare a sufficient quantity of hard, black bread to last until Spring. When Winter sets in in earnest the family lie down around the stove and go to sleep. Once in the twenty-four hours everyone wakes up, to nibble at a piece of the black bread, which is washed down with a drink of water. Then all go to sleep again. The members of the family take watch and watch about to keep the fire going.

This pseudo-hibernation lasts until Spring, or upward of six months, when the peasants take up their humble tasks again and are busy until the succeeding Witner, when silence reigns over the frozen land once more.

The writing is somewhat similar to the original 1900 article, but it's not clear whether the writer is the same. Searching for more information on this ancient art of lotska doesn't yield much new, so we're left wondering if the peasants really spent their long winters this way.

The accounts above are of people willingly undergoing depressed metabolism and what might be called a hibernation-like state, but what about people who fall into similar states by accident?

Fast forward about a hundred years, to 1999, when Swedish radiologist Anna Bågenholm got into a skiing accident which left her trapped under a layer of ice (link). For 1 hour 20 minutes, she was in freezing water, suffering the most extreme hypothermia ever recorded in a human. When she was rescued and taken to a hospital, her body temperature was a lethally low 13.7 °C.

After 40 minutes in the icy water, Bågenholm was in cardiac arrest. During cardiac arrest, the normal circulation of blood stops due to failure of the heart to contract effectively. As a result, oxygen is no longer delivered to the body and the brain, which leads to loss of consciousness. Brain injury usually happens after five minutes.

Strangely, despite minor symptoms related to nerve injury, no permanent brain damage was diagnosed in Bågenholm's case. One of the doctors treating her reported that "her body had time to cool down completely before the heart stopped. Her brain was so cold when the heart stopped that the brain cells needed very little oxygen, so the brain could survive for quite a prolonged time."

In 2006, a Japanese man named Mitsutaka Uchikoshi went missing during a mountain climb with friends (link). After leaving his friends to descend the mountain on his own, he tripped and lost consciousness. When he was found 24 days later, his pulse was almost non-existent, his organs had shut down and his body temperature was 22 °C.

Upon hearing his remarkable story, some doctors deemed it physiologically impossible that he had survived for so long without any water. His metabolism had apparently grinded to an almost complete halt. One of the doctors treating him commented: "He fell into a hypothermic state at a very early stage, which is similar to hibernation. Therefore, his brain functions were protected without being damaged and have now recovered 100%. This is what I believe happened".

In late December 2008, Magdeline Makola was abducted and tied up in a car boot (link). After 10 days of drifting in and out of consciousness in below-freezing temperatures, she was found by two traffic police officers. According to doctors, 48 more hours and she would've been dead; in a warmer temperature and she might not have made it through the 10 days. The hypothermia may have saved her life.

In a fascinating TED Talk from 2009, Ken Kamler describes the worst disaster in the history of Mount Everest, and the story of one climber's miraculous survival (link). Due to the fierce wind and extreme conditions, he was not able to return to the base camp from higher up in the mountain and instead just lay there in the snow, too weak to move.

Amidst the chaos, everyone presumed he was dead, until he burst into Kamler's medical tent seemingly out of nowhere, having forced himself to get up and trek back to base camp after 36 hours of being buried in the freezing snow.

Kamler tells the story as an example of the power of the human mind. The climber told him that while laying there in under the snow, he'd thought of his wife and child at home and decided that he couldn't just die there on the mountain. He had to survive for their sake. And so, severely frostbitten and suffering from hypothermia, he somehow managed to not only come back to life but to walk without help to base camp.

The human mind is undoubtedly capable of great things, but reading all these stories, I'm left wondering whether there is something else at play. A recurring theme in many of the cases seems to be that these people's metabolism was slowed down due to freezing temperatures and low oxygen. At mountain altitudes, for example, temperatures and oxygen are lower than at ground level. Even the yogis' tricks were done in small airtight spaces.

For the past years, cell biologist Mark Roth has examined the relationship between oxygen, metabolism and suspended animation. In 2005, he showed that mice exposed to small amounts of hydrogen sulfide put them in a state of hibernation, from which they could be brought back unharmed. The hydrogen sulfide caused the mice's core temperature to drop from 37 °C to 11 °C and their metabolism to slow by 90 percent. Hydrogen sulfide, which is naturally present in the body but toxic at large doses, works by preventing oxygen from binding.

Using freezing temperatures to induce hibernation is generally a bad idea in many species. Warm-blooded animals like humans react to cold by cranking up the internal heating system and burning more oxygen, which spells trouble. According to Roth, the key to lowering metabolism safely is to combine cooling with something that reduces the demand for oxygen (link):

I’m going to be talking [at TED] about unpublished work where we have demonstrated that if you make certain animals cold in an animated state, you kill them. But if you make those same animals cold, but they are now suspended, they all survive.

During the same TED Talk, he mentions experiments showing that if you reduce the oxygen content in the air slightly, roundworms die, and if you reduce it a lot – down to 10 ppm – they stop moving and appear dead but are in fact alive in a state of suspended animation. Unlike their animated and lively friends, these suspended roundworms can be put into cold temperatures without harm.

Exposing an organism to hydrogen sulfide is another way to achieve the same effect as reducing the oxygen content of a container or a room. By binding at the same cell site as oxygen, hydrogen sulfide reduces the need for oxygen, depressing metabolism. Roth theorizes that perhaps hydrogen sulfide production was increased in Bågenholm's own body when she fell under the ice, thus preventing her from dying from the cold.

The first practical application of this technique is surgery, which requires mild hypothermia to prevent harming patients. Even with a small amount of injectable hydrogen sulfide, which Roth's company has developed, the results are apparently better than with a traditional approach. Safety studies are already done, and human trials are underway.

While this is undoubtedly a great medical breakthrough, I can't help but think of other possible applications. What Roth has done is deanimate a mouse by reducing its metabolism and then bring it back to life unharmed. If the human trials are succesful, could this mean hydrogen sulfide might be used even outside surgery? Are we talking about a potential lightweight version of cryonics?

At this point, no one knows. Although similar findings have been confirmed by another lab using mice, two other labs reported that hydrogen sulfide did not induce hibernation in sheep or pigs (link, link), casting doubt on the feasibility of induced hibernation in large mammals.

Also, Roth didn't do lifespan experiments with his mice, so we don't know whether suspending them for longer periods of time might have made them live longer. But given that the connection between lower metabolism and extended lifespan has been shown in several other experiments, I certainly wouldn't be surprised if it did.

Makes you wonder if we could one day be like those poor Russian peasants, sleeping through the hard times and waiting for a brighter future.

For more information on technology and life extension, see these posts:

Biotechnology and the Future of Aging
How to Live Forever: My 5 Steps to Immortality
Aubrey de Grey in Helsinki, Finland
Anti-Aging in the Media: Rolling Stone on Ray Kurzweil

Read More......

Alternate-Day Feeding and Weight Loss: Is It the Calories Or the Fasting?

Weight loss with one slice of pizza one day and anything you want on the next? (Photo by nettsu)

I don't know if you noticed, but a new study on intermittent fasting recently made headlines in several media. The paper basically found that alternate-day fasting (or "on-off fasting" as it was named in some articles) helped obese adults to lose weight.

That's not a huge surprise, really. If you're obese, it means you eat too much of the wrong foods and probably too often. Fasting every other day means you'll at least be eating them less often, if not less per se. However, the conclusions that have been drawn in various articles from the study seemed a little suspicious to me, so I decided to read the whole paper.

Indeed, the authors themselves appear to be somewhat confused as to what really caused the weight loss. So without further due, let's take a closer look at what the study actually found (link).

Study design

12 obese women and 4 obese men were recruited for the study. Mean age was 46 years, mean body weight was 96.8 kg, and mean BMI 33.8. Not exactly the featherweight league.

The study consisted of three phases. The first one was a 2-week control phase, during which the subjects were told to maintain their usual weight by eating and exercising as they normally would. In the second phase, which lasted for 4 weeks, all participants were given a standard menu containing 25% of their baseline energy needs on the fast days. On the feeding days they could eat as much as they wanted. The third phase, also 4 weeks, was similar to the second one. The only difference was that the participants could choose what they wanted to eat on their fasting days, as long as they only ate 25% of their baseline needs.

So, the first thing that sets this study apart from how most people do intermittent fasting is that they didn't consume zero calories during their fast. They just ate significantly less. The second thing is that the fasts began and ended at midnight. Most people (including me) start and end their fast sometime during the day, because it allows them to eat at least once a day. If the participants went to sleep before midnight, their "fasts" were significantly longer than 24 hours.

Their standard diets were also less than optimal in my opinion. Things like chicken fettucini, vegetarian pizza, chicken enchilada, cookies, and crackers aren't exactly paleolithic foods consistent with the idea of intermittent fasting. But then, this wasn't a paleo study, which explains why they were fed high-carb, low-fat foods. For the third phase, they were given diet tips by a registered dietitian:

On the ad libitum food intake day, subjects were instructed to limit fat intake to <30%> dairy options.

So more carbs and less fat once again. They probably took some of this advice and applied for their feeding days as well, which makes me wonder if they wouldn't have lost even more weight had they opted for low-carb foods instead. Still, as you can see from the results below, they did manage to lose weight even with this diet.

Results

During the first phase, there was no weight loss. This is unsurprising, since all the participants just kept on eating whatever made them obese in the first place. During the eight weeks of alternate-day fasting they did lose weight, however.

In the second and third phase the subjects lost weight at a rate of ~0.7 kg per week. At the end of the study, they had lost about 5.6 kg, most of which was fat. Mean BMI decreased from 33.7 to 29.9, while body fat percentage dropped from ~45 to ~42%.

Cholesterol levels were also reduced as a result of alternate-day fasting. HDL remained the same, but LDL decreased by almost 25%. This to me is a more impressive result than the weight loss, which I think could've been greater with proper food choices.

Systolic blood pressure was lowered by 4.4 mm Hg, but diastolic blood pressure remained the same. Heart rates varied throughout the study, but at the end, they were about 4 beats per minute lower than in the beginning.

Discussion

Okay, so everyone lost some weight and improved their LDL/HDL ratio on this modified version of intermittent fasting. But what exactly is behind these results? The first thing that came to my mind as I was reading the paper was: how much were these people eating on their feeding days? Surely that would have a drastic effect on weight loss.

Unfortunately, there's no mention of this in the paper. Yes, they were told they could eat ad libitum, but apparently they were not told to keep a record of what or how much calories they ate when they were not fasting. I know food diaries are generally unreliable (people tend to underestimate how much they eat), but it would've been better than nothing. The authors seem surprised that the subjects lost as much weight as they did:

We predicted that subjects would lose a total of 4.5 kg fat mass after 8 wk (on the basis of a 75% decrease in energy intake on the fast day, with no change in energy intake on the feed day). The actual fat mass lost (5.4 kg) exceeded our predictions.

With no change in energy intake on the feed day? I'm not sure where the authors got the idea that when you eat very little on one day, the next day you won't be extra hungry and compensate. That's certainly not my experience. On the contrary, I fully compensate for any missed calories by just eating twice as much the next day. Certainly not compensating can be done if one wants to, which may be what happened here:

This indicates that these subjects were also limiting their energy intake on the feed day, which may have occurred because the subjects knew they were enrolled in a weight loss trial.

On the other hand, some articles in the media (such as this one) have reported that there was a slight compensation going on:

On non-fasting days people typically ate between 100 percent or 125 percent of their calorie needs.

This statement is probably from a press release by the authors, but the paper itself is silent on the issue. In any case, if you're eating 75% less on one day and only 25% more the next, you're still 50% short.

That, in effect, makes this a study on caloric restriction, not intermittent fasting. How is it surprising in any way that people who eat half (or even less) than what they're used to manage to lose weight? Isn't that obvious? The amount of weight they lost is pretty much what you'd expect on a low-fat, calorie-restricted diet. And based on other studies, if they'd eaten more calories but restricted carbohydrates, they'd have lost more weight.

The whole point of intermittent fasting is that you don't have to restrict your energy intake, you just don't eat all the time. If energy intake is the same and yet there are health benefits, then we can conclude that it's the fasting that is behind them. If, at the same time, calorie intake is restricted, there's no way of knowing whether it's the reduced calories or the fasting that is the cause. And of course, if intermittent fasting leads to a voluntary reduction in energy intake, that tells us something too.

I have a feeling that eating the small meal every other day magically resulted in no hunger in this study. They were probably consciously limiting their food intake even though they were told they could eat as much as they want. The fact that the authors actually expected the participants to eat only their usual calories on feeding days makes me even more suspicious.

Try eating 500 kcal on one day and then seeing how you feel the next day. If you typically eat 2,000 kcal, somehow I don't think 2,500 kcal is going to cut it. I know it doesn't for me, at least not in the long term. As for this diet being much easier to follow than old-school calorie restriction (which the paper seems to suggest), I doubt it.

For more information on intermittent fasting and caloric restriction, see these posts:

Intermittent Fasting: Understanding the Hunger Cycle
Slowing Down Aging with Intermittent Protein Restriction
Caloric Restriction Improves Memory in the Elderly
Intermittent Fasting Reduces Mitochondrial Damage and Lymphoma Incidence in Aged Mice

Read More......

Slowing Down Aging with Intermittent Protein Restriction

One serving (140 g) of pasta contains 8 grams of protein. (Photo by ex.libris)

I've written a lot about the health benefits of caloric restriction and intermittent fasting on this blog. But what if those same benefits could be had by periodically restricting protein intake?

According to Ron Mignery, author of "Protein Cycling Diet" (which is free, by the way), staying away from protein every once in a while shares a lot of the health effects of caloric restriction and intermittent fasting. Obviously, protein cycling is much easier, because it's not the energy intake but the protein intake that matters. Here's a quote from the introductory chapter:

Protein cycling is intended as a way for you to live longer and healthier with minimal interference with your normal routine and diet. It is based on well-established observations that animals and people who have endured periods of famine have extended life spans compared to those who have not and on more recent observations that periodic protein restriction alone can accomplish the same thing.

The key to the benefits of protein cycling is autophagy, a process in which a cell consumes a part of itself for energy. Starvation is one way of inducing autophagy: since there is no external source of energy, the body begins to use its own cell material to keep things running smoothly. This also happens to be an effective way of getting rid of accumulated junk in the cells, something which is difficult to do otherwise.

Mignery argues that autophagy is the reason why calorie restriction (CR) and intermittent fasting (IF) work the way they do, and that by the same logic, protein cycling should extend life too. He also points out that protein cycling may be something we're evolutionarily adapted to:

Before we managed fire, our days were governed by the sun. In the tropics, the sun is down for 12 hours every day. Without fire, there is little to do in the dark but sleep. So our ancestors likely fasted at least 12 hours every night even if they ate continually throughout the day. A 12 hours fast with our ancestors' diet may have been sufficient to induce autophagy and perhaps they were already protein cycling.

So what does a protein cycling diet look like in practice? Mignery gives a lot of interesting calculations in his book, which I urge you to check out, but let's skip straight to the conclusion:

From the table we can see that 3 days a week of protein restriction would be sufficient to counteract an exponential accumulation that doubles every 2.5 years. This then is my most recommended regime: three 24 hour periods each week where very little protein is consumed.

Sound familiar? If you're a long time reader of this blog then it should, because three days of not eating protein per week is pretty much what the 24/24 hour cycle version of intermittent fasting (also known as "alternate-day calorie restriction" and "alternate-day feeding") looks like. Since you're not consuming any calories during a fast, you're obviously not consuming any protein either.

So, it seems that whatever benefits protein cycling has, intermittent fasting has too. But that is not the point, of course. The point Mignery makes is the opposite: that the benefits of intermittent fasting can be had without restricting all calories as long as you restrict proteins. Yes, you read correctly. Unlimited carbs and fat.

But before you order that vegetarian pizza with extra cheese to kickstart your protein fast, there's a small caveat: protein is in almost everything. And, unfortunately for our purposes here, only very little is needed to keep autophagy at bay:

A less active adult male of any weight or caloric consumption gets his minimal protein requirement when the calories he gets from protein exceed 4% of his total caloric intake.

For someone on an average 2,000 kcal diet, that would mean less than 80 kcal (or 20 grams) from protein is acceptable. Anything above that is a bad idea during a protein fast. Thus, commonly known protein-rich foods such as meat, fish, eggs, beans and lentils are obviously out of the question.

But even carbohydrate-based foods are surprisingly high in protein. For example, cooked pasta contains 6 grams of protein per 100 grams. Even rice, which has the lowest protein percentage of grains consumed in the Western diet, still has 2 g protein per 100 g. Even if you ate nothing but rice for your daily calories, you would get enough protein to prevent autophagy.

So you would have to be very careful in constructing your diet during the protein restriction periods. In practice, I think you would have to reduce total energy intake during a protein fast and choose foods that are low in protein. Fats and oils (with little to no protein) could be enjoyed liberally, while carbs (some of which come with fairly large quantities protein) would need more careful attention.

That said, if Mignery is right, protein cycling still seems easier than intermittent fasting – and much easier than caloric restriction. If you're unwilling to cut back on your total food intake or do zero-calorie fasting but would like to have some of the benefits associated with IF and CR, I encourage you to read the book. Perhaps you will find protein cycling a good place to start.

At this point, I'm not entirely convinced that either intermittent fasting or protein cycling will have the same benefits as caloric restriction, which has been studied more extensively and in a wider range of species. It's not clear to me that autophagy alone is the reason why CR works, or even why IF works.

That said, it does seem clear that autophagy has a wide range of positive health effects. Anything that reduces and reverses the accumulation of junk inside the body seems like a worthwhile effort to me. I suspect autophagy will continue to receive attention within the next few years.

For more information on caloric restriction and intermittent fasting, see these posts:

Intermittent Fasting: Switching from Alternate-Day Fasting to Condensed Eating Window
Intermittent Fasting: Understanding the Hunger Cycle
Caloric Restriction Improves Memory in the Elderly
Anti-Aging in the Media: New York Times on Caloric Restriction and Resveratrol

Read More......

Anti-Aging in the Media: New York Times on Caloric Restriction and Resveratrol

The monkey on the left has been on a caloric restriction diet for over a decade.

Caloric restriction (CR) has been shown to extend the lifespan in a range of species, but the most exciting study has been the one on Rhesus monkeys. The study, led by Weindruch and Colman, has been going on for more than 20 years now.

Last week, new results regarding the monkeys were reported, and New York Times published an article discussing whether they might be translatable into humans. Dr. Weindruch, quoted in the article, seems to be very optimistic:

The researchers say that now, 20 years after the experiment began, the monkeys are showing many beneficial signs of caloric resistance, including significantly less diabetes, cancer, and heart and brain disease. “These data demonstrate that caloric restriction slows aging in a primate species,” they conclude.

I'm fairly confident we will eventually see a statistically significant increase in maximum lifespan in the monkeys, but I think it's somewhat premature to state it as a fact while the study is still running. I guess 20 years of waiting for conclusive results is a lot even for a patient scientist.

Looking at the pictures of the calorie-restriced monkeys next to the normally fed monkeys, it's evident that something good is happening – or rather, something bad is being prevented. The CR monkeys do look healthier and, well, younger. Here's a couple of more pictures (with the calorie-restricted monkey on the left):




All in all, for everyone out there doing CR this study seems to be positive news. For many others, this is just the first step, however. Learning how calorie restriction works will perhaps be even more important than seeing that it works. Drugs and treatments that target the same pathways can then be developed without the need to reduce calorie consumption dramatically. The article mentions resveratrol as a possible substance to replace calorie restriction:

Few people can keep to a diet with 30 percent fewer calories than usual. So biologists have been looking for drugs that might mimic the effects of caloric restriction, conferring the gain without the pain. One of these drugs is resveratrol, a substance found in red wine, though in quantities too small to have any effect.

Dr. Weindruch said the study data offered “very encouraging” signs that resveratrol could duplicate in people some of the effects of caloric restriction.

It's important to note that "duplicating some of the effects of caloric restriction" is not the same things as extending lifespan. Yes, it may help people with diabetes live longer, but there's no evidence out there that shows resveratrol increases maximum lifespan in healthy humans or animals.

Not to bash on resveratrol, though; I think it's one of the most interesting supplements out there. It just won't make us live to see a thousand, despite what some people would have you believe.

For more information on caloric restriction and resveratrol, see these posts:

Anti-Aging in the Media: 60 Minutes on Resveratrol
Caloric Restriction Improves Memory in the Elderly
Green Tea Increases Weight Loss during Caloric Restriction in Rats
Anti-Aging in the Media: Houston Press on Caloric Restriction

Read More......

Green Tea Increases Weight Loss during Caloric Restriction in Rats

The catechins in green tea are not the only healthy polyphenols of tea. (Photo by Augapfel)

It's time for some more green tea news from the weight loss frontier. If you're planning on doing calorie restriction to lose weight, you might want to consider adding green tea to your daily menu.

In a recent study, Sogawa et al. compared the anti-obesity effects of two types of tea, green tea and Awa tea, on male rats. The rats were first put on a weight-gain phase, where they were fed good old lard along with their standard diet. Then, they were put on a 50% calorie restriction (CR) diet to induce weight loss. During the CR diet, the experimental groups were supplemented with 3% green tea extract or 3% Awa extract, while the control group was given no supplements.

Awa tea is a traditional tea from the Tokushima prefect in Japan. It is made by fermenting tea leaves with lactic acid bacteria. Interestingly, this results in a tea with less catechins than green tea but with a similar polyphenol content, which means that catechins are just one type of polyphenols in tea.

Results

During the calorie restriction period, all three groups lost a significant amount of body weight. The green tea and Awa tea groups lost ~25% more weight than the control group, with no difference between the two types of tea.

Body fat ratio remained the same in the control group but decreased by ~10% in both tea groups. Green tea and Awa tea supplementation also reduced visceral fat accumulation compared to the control diet.

Plasma insulin levels were slightly lower in the tea groups, but the difference was not statistically significant. This is interesting, since green tea has been shown to increase insulin sensitivity both in vitro and in healthy humans during exercise. On the other hand, plasma leptin, which is also associated with body weight and fat ratio in humans, was significantly lower in both tea-supplemented groups.

Conclusion

Calorie-restricted rats supplemented with green tea and Awa tea lost more weight and fat mass than non-supplemented rats. Green tea and Awa tea also decreased plasma leptin concentrations. No significant differences were seen between the two types of tea, suggesting that other polyphenols than catechins (which are mainly found in green tea) also have health benefits.

Although fat intake was similar in all three groups, rats supplemented with tea had larger amounts of fecal lipids, which suggests that green tea and Awa tea effectively inhibited the fat absorption rate.

For more information on green tea and weight loss, see these posts:

Green Tea Extract Enhances Abdominal Fat Loss from Exercise
Drinking 3 Cups of Green Tea Increases Plasma Antioxidant Activity in Humans by 12%
Green Tea Extract Increases Insulin Sensitivity & Fat Burning during Exercise
Green Tea Protects from Bone Loss in Female Rats

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