Eat Less- Live Long? Not so FAST..

Got it- to FAST? ūüėÄ
The past week has been a treat in terms of great talks on campus. At ASU we are super-lucky to have the Center for Evolution & Medicine, which holds weekly talks by amazing speakers.

First
February 18- Arizona State University

When I saw that the upcoming seminar was related to diet and eating..or more specifically¬†NOT¬†eating or “dietary restriction”, I of course RSVPd in a heartbeat.

“Eat breakfast yourself, share dinner with a friend, give the supper to your enemy”- Russian Proverb

I’ve been in fact fascinated with¬†caloric restriction for¬†years now Screen Shot 2016-02-20 at 1.30.46 PM.png(I wrote a whole¬†research paper on it in the first year of my master’s degree). You might have heard of intermittent fasting (e.g. popular in the CrossFit world), or the CR¬†Society (¬†http://www.crsociety.org/ )- all are related to¬†the concept that restricting food intake results in health benefits (from extending life to preventing and reversing disease).

I’m sure you can Google caloric restriction and find a bunch of information on its reported benefits..you would see this chart at the CR society website- the lifespan of calorie-restricted (CR) mice vs non-CR mice. You can see that those whose food intake was restricted by more & more % lived longer.¬†Screen Shot 2016-02-20 at 1.24.28 PM.pngWhy do many animals (and perhaps¬†humans) appear to be so well-adapted to eating less? The traditional interpretation of this CR phenomenon is that¬†the¬†dietary restriction effect “has¬†evolved as a way to enhance survival & preserve reproduction during periods of naturally occurring food shortage”. In other words- being adapted to do well on restricted food intake during rough times would have helped our ancestors survive them & stay healthy to have kids later when the food situation improves.

The traditional interpretation of this CR phenomenon is that¬†the¬†dietary restriction effect “has¬†evolved as a way to enhance survival & preserve reproduction during periods of naturally occurring food shortage”.

Experimental evidence with animals, however…supports a different hypothesis- the one Dr. Austad (Professor & Chair of the Department of Biology at the University of Alabama)¬†presented to us last week.¬†Again, I wouldn’t be able to cover everything he discussed during the seminar, but I do want to highlight a couple of main points!

I. First, even though the first book on dietary restriction (DR) HowWorks.jpgdates back to the late 16th century, we still do not know the mechanism behind why DR seems to extend life and vigor in animals + delay disease such as cancers. METABOLISM was the original suspect, as metabolic rate goes down with fasting.. however, metabolic rate drops initially yet gradually goes back UP (takes 6-8 weeks to happen).. Since DR changes an unbelievable amount of physiological parameters (see screenshot ->) it is very hard to determine its mechanism.

II. Second, while many sources cite mice experiments showing life extension with caloric restriction.. those experiments are done with lab mice. When DR studies are done with wild mice, DR has no effect on longevity. WHAAAT!! I’ve never heard this before- in fact i was under the impression that CR/DR extends life in animals, period. Well, NO STUDY has ever found that DR extends life or improves health in nature (or even “nature-like” conditions). Mice in the wild actually do not have enough fat stores to reduce feeding except very briefly (wild mice has about 4% fat while a regular lab mice has 15%; also lab mice do not reproduce). In fact, mice in nature simply do not live long enough for the survival benefits of DR to be important. Another challenge to the original hypothesis that adaptation to dietary restriction¬†enhances survival, is that DR increases¬†mortality from some infections. Lastly, DR increases cold sensitivity (and cold is a major source of death in wild mice) and slows down wound healing.

Sounds like animals in the wild would not benefit from adaptation to dietary restriction… yet¬†why¬†is the positive DR effect observed in so many studies so common?

III. Well, even though wild mice do not live longer with restricted diets, DR still results in cancer protection for them. But even more importantly, DR has been found to protect against acute effects of many many toxins! Dr. Austad talks about this discovery in the following way:

¬†..¬†if animals can not afford to wait to reproduce..and they have to do it even when food conditions are poor, what they will do is broaden their diet. This means they might be ingesting a lot of toxins they are not normally exposed to (foods infected with fungi, new seed types that are well defended by the chemicals they wouldn’t normally encounter). So the hypothesis is that DR acutely induces broad defense mechanisms from a broad range of toxins

Toxicology studies have shown that mice that are calorically restricted survive a wide range of toxins. DR also acts as an acute (vs. chronic) protectant against other problems (see slide below). Renal ischaemia reperfusion injury (IRI) is a common cause of acute kidney injury and we can see that while ad libitum mice are dying steeply by day 7, those on DR of various proportions survive (30% DR is only 70% of normal food intake; ad libitum stands for eating as much as one wants). This is quite impressive!!!

Screen Shot 2016-02-20 at 2.36.43 PM.png

These acute benefits of DR have very important implications. We can think about these effects actually protecting the body against the toxins it itself produces (like free radicals).. it also has clinically relevant advantages- e.g. patients on very strong drug cocktails fasting to avoid harsh side-effects. This suggests that the protective effects of DR could have clinical relevance unrelated to chronic benefits like life extension.

The new hypothesis explaining the evolutionary advantage of this paradoxical effect is that dietary restriction arose as a defense against novel exposure to toxins during food shortage.

So in conclusion.. we saw evidence suggesting that dietary restriction would NOT enhance survival in nature. Yet research has shown that DR increases health and life in a diversity of species. The new hypothesis explaining the evolutionary advantage of this paradoxical effect is that dietary restriction arose as a defense against novel exposure to toxins during food shortage.

Screen Shot 2016-02-20 at 2.54.15 PM.png

My conclusion? I’m still excited about this topic- more than ever before!!!¬†There is a lot of work done now on the timing of food intake as well (not just restricting the amount, but restricting the timing of eating and human health) and I can’t wait to post more about this (after I collect some necessary data though :). ¬†Watch out for early May as I’ll be sharing some more info!

PROTEIN

Finally I get to post about something not too many people are questioning..Protein overconsumption! ūüėÄ

Whether I talk to a body-builder or a dietician, health effects of eating too much protein do not seem to be on anyone’s radar (unless a kidney disease is suspected).

Beef it up!
In developed countries people are eating approximately 30% more protein than the RDA recommended intake (1.2g of protein/kg of body weight/day vs. 0.83g RDA). Yet this is considered harmless or even beneficial (for satiety, obesity prevention). In general, we can think of all kinds of anti-fat or anti-sugar arguments, yet protein seems to be the nutrient we don’t need to worry about. There are many protein-enriched snacks and drinks that seem to have a health halo effect. I think people are not even sure why the label claim “x grams of protein!” seems exciting or promising some sort of a benefit (unless one is a gym enthusiast). Perhaps it is the fact that we don’t know any “bad” health effects of this nutrient.

Longevity & health studies
In terms of living longer, calorie restriction(CR) is the only non-genetic intervention that can lead to life extension in different organisms (from yeast to rodents to monkeys and supposedly humans). Calorie restriction means reduced energy intake (moderate CR is about 30% less calories than recommended) without malnutrition. Studies on the famous Okinawa centenarians suggest it is their moderate eating that contributes to health and longevity.
So CR should not be confused with starving or extreme undereating- many people and cultures might do so without much thought- eating about 1700 calories/day for a person with 2000 being a goal is already calorie restriction.

In mice CR studies, general CR increases longevity and induces a reduction in the level of IGF-1 (insulin-like growth factor 1). IGF-1 is an important growth factor that mediates the growth of cells and inhibits apoptosis (cell death); it is IMPORTANT because there is considerable evidence that a reduction in IGF-1 signaling plays a key role in modulating cancer and aging in humans and rodents. HOWEVER, for us humans CR does not reduce IGF-1 concentration unless protein intake is also reduced. This suggests that protein intake is more important than calorie intake in terms of IGF-1 levels in humans.

Median protein requirement for a healthy adult, by the way, is 0.65 g/kg/day. Decreased protein intake discussed with CR does not go below this number.

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mTOR
I first came across the idea of not going crazy on the protein while reading about mTOR. The mammalian target of rapamycin (mTOR) signaling system seems  to be connected with aging and cancer
development (also cardiovascular and neurodegenerative diseases). The insulin/IGF-1/mTOR pathway is downregulated by calorie restriction, and in turn activates other anti-aging pathways in mammalian cells.

Conclusion
It is necessary to see more human studies with caloric and protein restriction and the effect on health and longevity. We all know overeating is not great- it does lead to weight gain and associated health issues. But it also might be speeding up our aging, wear&tear, and increasing chances of various chronic diseases. This could be crucial for a culture that believes protein to be a healthy macronutrient which needs no limitation ūüėČ

Some LINKS:

Why Protein is the new “It” Ingredient

http://online.wsj.com/article/SB10001424127887324789504578384351639102798.html

Macronutrient Balance and Lifespan

http://www.impactaging.com/papers/v1/n10/full/100098.html