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The Myriad Benefits of Intermittent Fasting
Posted By Mark Sisson On February 16, 2011 @ 9:30 am In Aging,Fasting,Gene Expression,Health,Prevention | 301 Comments
Calorie restriction  is all the rage in anti-aging circles. A few mice and worm studies seem to show that drastic reductions in food intake over a long period of time have the effect of prolonging life – although I’m not sure I’d call it living. For one, these animals are actually restricted. There’s no ad libitum access to food. They’d prefer to eat more, but are prevented from doing so. I guarantee you they’re unhappy and, if they could put (cartoonish high-pitched) voice to physiological state, would say they’re starving.
Anyway, humans have picked up on this calorie restriction stuff. You might have seen one or two CR gurus giving TED  talks; the exposed rib cages, gaunt faces, and complete lack of lean muscle mass  are dead giveaways. Okay – that’s a bit unfair. CR is a legitimate way to improve many health markers. I’m just not convinced actively restricting your calorie intake through sheer will is the true path to enjoyable longevity. I’d rather be robust, vibrant, and full of zest. I want to eat big strapping meals of steak  and veggies smothered in butter  without counting calories. On occasion, I like to devour an entire roasted chicken (yeah, yeah, chicken has more omega-6 than most animals, but I’ll live). I want to maintain muscle mass and have enough energy to go on long hikes  and have the legs to still leap for high passes (over the young guys) at the end of Ultimate games . And as I appreciate the neuroprotective and autophagy-promoting qualities of calorie restriction, I’d rather not expend the mental energy and fortitude required to maintain such a regimen day-in and day-out. Nor would I willingly subject myself to forced calorie restriction, a la the lab mice. No human-sized rat cages for me, even if they include a salt lick and a running wheel (don’t get any ideas, Blaisdell ). Based on the science, I don’t think all that is necessary. I’ll just IF  instead.
Fasting is one way to have your cake and eat it too. Beyond the already proven benefits of a Primal Blueprint low-carb lifestyle, fasting once in a while seems to offer many of the same benefits of calorie restriction – you know, stuff like increased longevity, neuroprotection, increased insulin sensitivity, stronger resistance to stress , some cool effects on endogenous hormone production, increased mental clarity, plus more - but without the active, agonizing restriction. You just eat Primally , focusing on meat and vegetables with plenty of animal fat , and skip meals  on occasion. A sixteen-hour fast is on the low-but-still-effective end (you could easily maintain a daily sixteen hour IF regimen, giving you an eight hour eating window, a la Leangains ), or you could opt for longer, more intermittent fasts – say, a full twenty-four hours once or twice a week. When you’re done with the fast, eat as much as you want (which usually isn’t an issue, once you’re PB-adapted). It essentially turns into “eat when you’re hungry,” because let’s face it: eating the types of foods we evolved eating induces powerful satiety  and makes eating the right amount of food a subconscious act. Fasting becomes a whole lot easier (and intuitive) when you’ve got your food quality dialed in. And I’ll come back to that little caveat at the end here.
“Fasting” was the top search term for MDA last week, and I hadn’t done a big post on it in a while, so I thought I’d do a comprehensive rundown of all the benefits (some conclusive, others prospective) you can expect to obtain from IF.
Everyone wants to live longer, but I find longevity pointless if you’re not enjoying yourself . Otherwise, life becomes dreary. Consider the plight of the vampire – he lives a long, lonely life, never really connecting with anyone, never really enjoying all the time he has at his disposal. If the suggested longevity benefits of fasting pan out, I think we can enjoy the vampire’s longevity (and perhaps even some of his incredibly immune and restorative properties) without the downsides. Oh, and we’ll eventually have to die, but we have the option of sunbathing.
The popular c. elegans worm enjoys increased longevity  with both twenty-four and forty-eight hour IFs via signaling through a gene that we all have.
One study (full PDF ) from the 1940s found that varying amounts of twenty-four hour IFs (every other day, every fourth day, every eighth day, etc) prolonged the lifespan of rats without retarding or stunting the growth (as occurred with calorie restricting them). Female rats responded best to every eight day fasts, while males responded best to every other day fasts.
Reductions in brain insulin signaling have been shown to increase lifespan in animals, either by calorie restricting or actively knocking out brain insulin receptors . Fasting also reduces brain insulin signaling, at least in rats .
Going in and pharmaceutically manhandling your cholesterol synthesizing equipment  is one thing; eating real food and exercising, resulting in possible alterations to your lipid profile , is another. We don’t set out to force your blood lipids into submission, but lifestyle changes that happen to change them for “the better” are usually a good thing. Fasting brings potent changes to blood lipids in an “organic” way – you’re just letting your machinery do its thing on its own – and this is probably a very good thing.
IF is as or more effective than calorie restriction  in improving metabolic syndrome markers in overweight women, and it’s a whole lot easier to stick with.
Alternate day fasting improved cardiovascular risk markers , including lowered triglycerides and LDL-C numbers (although it’s unclear whether the improvements were related to the weight loss alone or something unique to fasting).
I discussed this last week, but it can’t hurt to mention that short-term alternate day fasting  wrought improvements in LDL particle size and distribution in obese adults.
A dietary regimen is useless without compliance. In fact, that’s what we’ve always said about the low-fat, low-calorie diet advice we’re inundated with: sure, they might work, but they’re impossible for most people to maintain. Eating Primally solves this problem, because it’s simple, easy, delicious, and satiating (you just have to enjoy cooking, or learn to), and IF is another compliance-breeding regimen that blends quite nicely with the PB . A lot of Primal eaters find that fasting just kinda happens without them setting out to do it, so it’s not even a conscious struggle. Check it out:
The obese (read: the ones who need the most help and often have the worst time sticking to a diet) were able to “quickly adapt”  to alternate day modified fasting, which meant on fasting days they’d get 26% of their normal caloric intake. They were also able to maintain physical activity despite the fasting.
Heck, intermittent fasting even helped cocaine addicts stick to their treatment  and rehab program. Not bad.
The notion of IF reducing cancer incidence and improving survival is compelling, but little evidence in humans exists. Ketogenic diets may also offer exciting potential for cancer patients, and both IF diets and ketogenic diets share something: fat (either dietary or from your own adipose tissue) as primary fuel sources. But, while ketosis isn’t exactly desirable or optimal as a lifelong dietary regimen, IF is sustainable, simple, and can be integrated into your current diet. As of now, most of the evidence for IF’s protective effects against cancer exist in animal trials, mostly using mice. Still, fasting seems to confer so many other benefits that working it into your life for its anti-cancer potential is probably worth it. Some of the evidence:
Calorie restriction is proven to fight cancer cell proliferation in mice, but researchers found that intermittent fasting was just as effective . In fact, here’s a review of most of the animal anti-cancer evidence . It’s quite compelling.
Some researchers are speculating, based on substantial evidence, that fasting before and during cancer treatment should result in reduced morbidity, better tolerance of chemotherapies, and higher cure rates . This is refreshing news. A preliminary study  in human cancer patients found that fasting during chemotherapy reduced the negative side effects of the treatment. The authors are quick to point out that the results are in no way a prescription for fasting in chemotherapy patients and that controlled trials are needed to change official recommendations, but that doesn’t mean you – the individual – can’t experiment.
Aging humans “normally” experience reductions in growth hormone. While it’s true that unchecked growth hormone can lead to unwanted cell proliferation (like, ya know, cancer), growth hormone therapy can really help stave off the doldrums of old age. Luckily, short-term fasting induces growth hormone secretion  in “normal men.” I’m not for mainlining GH or anything, but I’m all for amping up my own production. Furthermore, a recent study  found that resistance training actually blunted hunger for an hour. I’ve found this to be the case for me. If the body “needs” food right after a workout, why would hunger be blunted? This is why I tend to hold off on the eating post-workout. Every little bit helps, especially as you age.
Fasting doesn’t cause your brain tissue to waste away, contrary to what some people will tell you. It’s actually good for brain health. Any dietary restriction tends to increase neuronal plasticity and promote neurogenesis, but it was IF that had the greatest effect  (with the fewest downsides). Another study of mice found that meal frequency impacts neuronal health . That is, mice who ate larger meals more infrequently saw greater increases in brain and overall bodily health. Still another study found that IF was beneficial for peripheral nerve function in mice by promoting the maintenance of the neuronal pathways responsible for locomotor performance . It’s almost like this stuff just puts your brain in repair, or maintenance mode.
Fasting turns on autophagy (most studies nowadays treat this as common knowledge ), which is the process by which cells recycle waste material, eliminate or downregulate wasteful processes, and repair themselves. Why is autophagy so important? It’s required to maintain muscle mass , and inhibiting it induces atrophy of adult skeletal muscle . It reduces the negative effects of aging  and reduces the incidence and progression of aging-related diseases. In fact, researchers have determined that autophagy is the essential aspect of the anti-aging mechanism of fasting . Without the autophagy that fasting provides, you would get very few of the benefits. Fasting even increases neuronal autophagy , which aids in maintaining mental health and function. Short term fasting, too. No marathon thirty-six hour fast required.
You’ll hear that you should never exercise on an empty stomach. You’ll hear that fasted training will burn your muscles and cause you to waste away. You’ll hear that performance will surely suffer. None of these things are necessarily true – and they are even less so if you are well-adapted adapted to a low-carb eating strategy. Fasted training can actually result in better metabolic adaptations  (which mean better performance down the line), improved muscle protein synthesis , and a higher anabolic response to post-workout feeding  (you’ll earn your meal and make more muscle out of it if you train on an empty stomach). Studies on Muslim athletes during Ramadan show no effect on performance while fasting , as well as better lipids  in those who exercise and fast rather than just fast. When you train in a fasted state, glycogen breakdown is blunted  and more fat is burnt, leaving you more glycolytic energy in the tank for when you really need it and less body fat. Those are just a sampling of the benefits to fasted training; there are dozens more. Check out Martin at LeanGains (linked above) for more information on fasted training. It’s his specialty.
You’ve heard this “advice” before, probably from an expert dietitian in some copy-and-paste article on healthy living on Yahoo! Health. It’s the mantra of the high carb crowd: failure to eat something every few hours will cause mental fog  and sluggishness, so keep a banana or a granola bar on your person at all times. Of course, this is all based on an assumption that we need to supply exogenous carbs on a regular basis to properly fuel the brain. This notion that fasting is only the province of anorexics or “those crazy caveman dieters” has kept many people from experiencing the myriad benefits.
I maintain that one’s comfort in handling IF effortlessly does increase dramatically when you’ve reprogrammed those cells (and genes) to predispose your body to derive most of your day-to-day energy from fat , as opposed to constantly dipping into glycogen  stores (as happens when we rely so much on refeeding carbs every few hours). It’s also why I recommend that you eat according to the PB for at least three weeks before you really start incorporating IF on a regular basis. I’ll be discussing this detail more in upcoming posts on IF and what I am calling “the Metabolic Paradigm Shift”.
Overall, fasting just seems right. It’s like a reset button for your entire body, presumably across a large spectrum of maladies and dysfunctions. It puts your body into repair mode – at the cellular level – and it can restore normal hormonal function in the obese or overweight. Now, you don’t have to fast, but it’s definitely something to consider. As I said, I don’t plan my IFs – I let them happen. I prefer to fast when it’s forced upon me, like when I’m traveling or under a deadline. Once you’re acclimated to the Primal Blueprint diet, give it a shot and report back. Obviously, you won’t know if you’re fighting budding cancer cells or turning on autophagy in your brain, but if you can tolerate fasting and even derive some subjective benefits, those potential long-term benefits make it a worthwhile addition.
Have you tried IFing yet? Did you have a great, transcendent, middling, or perhaps even awful experience? Let me know how intermittent fasting has worked – or hasn’t – with your lifestyle in the comment section!
UPDATE: See this post on Women and Intermittent Fasting .
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 Blaisdell: http://pigeonrat.psych.ucla.edu/
 IF: http://www.marksdailyapple.com/fasting/
 stress: http://www.marksdailyapple.com/cortisol/
 eat Primally: http://www.marksdailyapple.com/definitive-guide-to-the-primal-eating-plan/
 animal fat: http://www.marksdailyapple.com/yet-another-primal-primer-animal-fats/
 skip meals: http://www.marksdailyapple.com/how-to-intermittent-fasting/
 Leangains: http://www.leangains.com/
 powerful satiety: http://www.marksdailyapple.com/curb-your-appetite-high-fat-diet/
 if you’re not enjoying yourself: http://www.marksdailyapple.com/thrive-survive/
 enjoys increased longevity: http://www.ncbi.nlm.nih.gov/pubmed?term=RHEB-1
 full PDF: http://jn.nutrition.org/content/31/3/363.full.pdf
 actively knocking out brain insulin receptors: http://www.ncbi.nlm.nih.gov/pubmed/18948730
 at least in rats: http://www.ncbi.nlm.nih.gov/pubmed/21244426
 pharmaceutically manhandling your cholesterol synthesizing equipment: http://www.marksdailyapple.com/monday-musings-torcetrapib-part-deux-and-keto-diets-seize-the-day/
 lipid profile: http://www.marksdailyapple.com/cholesterol/
 IF is as or more effective than calorie restriction: http://www.ncbi.nlm.nih.gov/pubmed/20921964
 Alternate day fasting improved cardiovascular risk markers: http://www.ncbi.nlm.nih.gov/pubmed/20300080
 short-term alternate day fasting: http://www.ncbi.nlm.nih.gov/pubmed/20880415
 PB: http://www.marksdailyapple.com/definitive-guide-primal-blueprint/
 were able to “quickly adapt”: http://www.ncbi.nlm.nih.gov/pubmed/20815899
 even helped cocaine addicts stick to their treatment: http://www.ncbi.nlm.nih.gov/pubmed/20456017
 researchers found that intermittent fasting was just as effective: http://www.ncbi.nlm.nih.gov/pubmed/18184721
 review of most of the animal anti-cancer evidence: http://www.ajcn.org/content/86/1/7.full
 fasting before and during cancer treatment should result in reduced morbidity, better tolerance of chemotherapies, and higher cure rates: http://www.ncbi.nlm.nih.gov/pubmed/19135806
 preliminary study: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2815756/?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_SingleItemSupl.Pubmed_DiscoveryDbLinks&ordinalpos=1&tool=pubmed
 short-term fasting induces growth hormone secretion: http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=1548337&ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
 recent study: http://ajpregu.physiology.org/content/296/1/R29.full
 IF that had the greatest effect: http://www.ncbi.nlm.nih.gov/pubmed/12558961
 frequency impacts neuronal health: http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.01586.x/full
 promoting the maintenance of the neuronal pathways responsible for locomotor performance: http://www.ncbi.nlm.nih.gov/pubmed/19320048
 most studies nowadays treat this as common knowledge: http://www.ncbi.nlm.nih.gov/pubmed/21106691
 required to maintain muscle mass: http://www.ncbi.nlm.nih.gov/pubmed/19945408
 inhibiting it induces atrophy of adult skeletal muscle: http://www.ncbi.nlm.nih.gov/pubmed/20104028
 reduces the negative effects of aging: http://www.ncbi.nlm.nih.gov/pubmed/16973211
 autophagy is the essential aspect of the anti-aging mechanism of fasting: http://www.ncbi.nlm.nih.gov/pubmed/17934054
 even increases neuronal autophagy: http://www.ncbi.nlm.nih.gov/pubmed/20534972
 better metabolic adaptations: http://www.ncbi.nlm.nih.gov/pubmed/21051570
 , improved muscle protein synthesis: http://www.ncbi.nlm.nih.gov/pubmed/20720176
 higher anabolic response to post-workout feeding: http://www.ncbi.nlm.nih.gov/pubmed/20187284
 no effect on performance while fasting: http://www.ncbi.nlm.nih.gov/pubmed/19085449
 better lipids: http://www.ncbi.nlm.nih.gov/pubmed/19787180
 breakdown is blunted: http://www.ncbi.nlm.nih.gov/pubmed/18276898
 mental fog: http://www.marksdailyapple.com/low-carb-flu/
 fat: http://www.marksdailyapple.com/fats/
 glycogen: http://www.marksdailyapple.com/glycogen/
 Women and Intermittent Fasting: http://www.marksdailyapple.com/women-and-intermittent-fasting/
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