Mechanism Posted November 22, 2016 Report Share Posted November 22, 2016 Edited Link to comment Share on other sites More sharing options...
mccoy Posted November 22, 2016 Report Share Posted November 22, 2016 A rigorous water-only fast would include only... water, without limit. Traditionally, a few drops of fresh lemon juice in water are allowed, if it's needed to make the water more palatable. That's all. No coffee, tea, broth, nor pills, drugs and so on. Is it possible to develop dyspepsia while fasting? Not eating at all should be the foremost remedy against dyspepsia since the stomach just rests, unless there are leftovers from a huge binge. A single day to start out with is good, what I'd do is take no drugs unless really necessary. It's not advised to start out with a 5 days fast, better to repeat and lenghten gradually, unless the body tolerates it well. Link to comment Share on other sites More sharing options...
Michael R Posted November 22, 2016 Report Share Posted November 22, 2016 I'm pretty skeptical of the whole notion of hormesis as a scalable variable. Indeed, it's been shown very clearly that the effects of IF are exactly reducible to the degree of concomitant CR, with no added benefit of the presumed increase in stress accompanying the IF paradigm. See discussion here (including my followup here) on IF in general, and here for more and for discussion on Longo's recent "Fasting Mimicking Diet." Irrespective, however, diphenhydramine (Benzadryl etc), meclizine, and other first-generation antihistamines should not be used as sleep aids, or indeed for any purpose other than occasional relief of bad nighttime allergy attacks. There are now multiple prospective studies linking long-term use of these and other anticholinergic drugs (including tricyclic antidepressants like amitriptylene) with cognitive decline and dementia (eg. PMID 25621434, and studies cited therein; PMID 23183138; PMID 26976294). Link to comment Share on other sites More sharing options...
Mechanism Posted November 24, 2016 Author Report Share Posted November 24, 2016 Edited Link to comment Share on other sites More sharing options...
mccoy Posted November 24, 2016 Report Share Posted November 24, 2016 I'm going through the discussion referenced by Michael as well, which I didn't read previously. It is interesting to read about the criticism to Longo's studies. I have no specific decisional tools here since my background is not biological & medical science. I just listen to different opinions and experiment myself in a sort of Bayesian process, having a substantial a-priori wealth of data on my own body (based on 40 years of supposedly healthy lifestyle and nutrition). Sometimes, as it is inevitable and barring factual falsification, I also follow my intuition and mental proclivities. For example, I'm not attracted by mere CR simply because I'm not attracted by too thin a body. I'm reading that many CR practitioners here have a BMI of 18 or less. I rather like a muscular build, out of cosmetic and practical/functional reasons, let's say nothing below a lean 22 BMI, what I am now, but my target is at least 24. This mental viewpoint of course will influence my choices. I'll rather choose restricted severe CR but return to my original weight than undergo long and mild CR and remain with a very low BMI. The above of course assuming MPS cannot substantially occur during CR proper but it may not be so. That's why I tend to reason (and I might be wrong here) in terms of simple protein optimization and subordinately carbohydrates optimization as a means to keep the mTOR and IGF-1 pathways/axes downregulated. Also, I'm attracted by the idea stem cell based regeneration and rejuvenation of the immune system which Longo and collaborators contend is happening after FMD. Link to comment Share on other sites More sharing options...
Sthira Posted November 24, 2016 Report Share Posted November 24, 2016 I am about to embark on my first ever fast ( unless you count skipping breakfast as a fast). Are you aware of any data ( or would you practice) for optimal hormesis and health benefits, should melatonin, antihistamines such as diphenhydramine or meclizine, and/or all sleeping aids be avoided? How about antacids and/or pepto-bismol should I develop dyspepsia during the fast? I'm also wondering if any herbal or regular teas can interefere with the health benefits / hormesis or even spices for that matter since I have used basil, oregano, parsley, rosemary, onion/garlic powder and other nontraditonal herbs to flavor tea along with the more common agents such as tumeric, and cinnamon. I may adapt this as an annual spiritual practice of sorts ( Partially inspired by Sthira ). My goal is minimum of 1 day, maximum of 5 days water only fasting. I am aware of Valter Longo's 5-day FMD, but with my temperament I would prefer 1 day of a pure fast over an extended partial fast. I know there is lots to google, but other tips, references, and suggestions from amateur and veteran prolonged fasters appreciated from the collective wisdom here. My takeaway from Longo's work (broad interpretation here) is that food and eating are stressors on the body. Going without food is our natural, adaptive state. Without food, the body is triggered to a program of regeneration. Refeeding then signals the system to rebuild some of those damaged parts, then we resume our regularly scheduled program geared toward reproduction. Fasting for sufficient time periods may tear down broken and damaged cells; refeeding after prolonged fasting may then repair some of that damage. Big ifs here, but the benefits of fasting may arise from the refeeding. Of course it's all nuanced, and it all depends on who, what, where, why, when, and how. Yet the science gig -- attempting to understand and quantify fasting coupled with refeeding -- seems more like art. The science appears too difficult for scientists to accomplish, or maybe there's just not enough financial incentive or funding for scientists to get very far. So until there's AI, it'll likely remain an art with maybe a creeping advance or insight here and there for those of us seeking hints. Collectively, we'd all just rather just take some lab pills or sign on for some future injections, or whatever. Support SENS. Meanwhile, while awaiting the miracles ahead, I've practiced both calorie restriction with "optimal nutrition" (cronometer inspired weighing and documenting) and fasting with optimal nutrition (RDA-ish feeding). And what I find more convincing with periodic, prolonged fasts is that my body remains much stronger and feels healthier when practicing fasting and refeeding cycles. Chronic calorie restriction leaves me chronically weak, and weakness is not sustainable here. So I quit CRON because I must function in an athletic environment in order to make a living. I'm not in a cage like a mouse or a macaque in a science experiment. I'm not in a cubicle or behind a desk like an office worker. If I was jailed and sedentary, then chronic CR combined with prolonged fasting might work, too. My goal is minimum of 1 day, maximum of 5 days water only fasting. I am aware of Valter Longo's 5-day FMD, but with my temperament I would prefer 1 day of a pure fast over an extended partial fast. One day without food isn't fasting. One day without food is just sorta delayed eating. By days three or four without eating (depending upon you and your situation) you're just entering the "therapeutic" value of fasting. The regenerative aspects are just beginning after days three, four, five, so why stop the program at day one? By day five you're just getting started. Your temperament says you prefer one day of fasting to five. Well, everyone else's temperament would prefer less discomfort to more discomfort, too. However, if give longer fasts a try, you just might discover they're less uncomfortable than you may have anticipated, and even, um, fasting might become pleasurable and empowering. Also, a two or three day fast in a mouse (if mice are even applicable to people in this context) requires much longer time spent prolonged fasting for people -- ha, more like seven to ten days, and probably much longer for us. A mouse may lose, what, up to a quarter of its body weight during a 48-hour fast? Haha, I won't lose a quarter of my body weight during a one to five day fast. By days three or four, I'll just begin to enter ketosis -- and ketosis is an unmistakable sensation I don't experience on CR -- and I may lose about a pound per day of water weight. Then I'll regain the lost water when I return to my regularly scheduled diet and exit ketosis (exiting ketosis is another unmistakable sensation I don't experience with CR). I'm also wondering if any herbal or regular teas can interefere with the health benefits / hormesis or even spices for that matter since I have used basil, oregano, parsley, rosemary, onion/garlic powder and other nontraditonal herbs to flavor tea along with the more common agents such as tumeric, and cinnamon. If by "interfere with the health benefits..." you mean kick me out of ketosis, then no. For me, I've no problem drinking teas, coffee, or water with vinegar when fasting. I avoid the antihistamines, supplements, and herbs you've listed, and I also avoid food and any liquid that might send me out of ketosis. Ketosis isn't subtle -- I know when I'm in it and I know when I'm not. I've tested with keto blood strips, they're too expensive, so fuck them. Listen to your body. The entire practice of fasting probably isn't doing much to prolong my lifespan. Prolong health span perhaps, big maybe, big if? Delay the known diseases of mod excess? Increased lifespan for us will come out of future storied clinics. Eventually. While tinkering around with fasting and delayed eating is fun and interesting "for spiritual reasons," like you wrote, I have no illusions that fasting is increasing my lifespan. I view as the best option I've got. A rigorous water-only fast would include only... water, without limit. Traditionally, a few drops of fresh lemon juice in water are allowed, if it's needed to make the water more palatable. That's all. No coffee, tea, broth, nor pills, drugs and so on. Any ideas who created these rules and why? I'm not trying to be provocative, I'm just curious because I see this inflexibility often repeated but rarely explained sufficiently. quote name="mccoy" post="19662" timestamp="1479851079"] It's not advised to start out with a 5 days fast, better to repeat and lenghten gradually, unless the body tolerates it well. I agree with this, that the going gets easier as the going gets going. We get better with practice. Indeed, it's been shown very clearly that the effects of IF are exactly reducible to the degree of concomitant CR, with no added benefit of the presumed increase in stress accompanying the IF paradigm. . I can't speak to IF (intermittent fasting like 16:8?) but do you enter into ketosis while practicing calorie restriction? I never did, or at least couldn't feel it, and I perceive that something very different is happening within my body while prolonged fasting. Also, Longo's work appears to argue that fasting isn't stress. Fasting is what we did for the majority of our evolution. Eating is what's stressful on the body. The primary benefits of fasting, he argues, derive from refeeding which triggers a program of regeneration not seen via calorie restriction exclusively. But of course we're talking about mice and a few handfuls of people under very specific circumstances, so whatever. Subjectively, though, something very different happens with prolonged fasting. Also, I'm attracted by the idea stem cell based regeneration and rejuvenation of the immune system which Longo and collaborators contend is happening after FMD. Me, too. Until more evidence pokes up, I'm not married to any dogma and willing to stay quite flexible. But I'm bothered that Longo's work hasn't been replicated by other workers yet. Link to comment Share on other sites More sharing options...
mccoy Posted November 24, 2016 Report Share Posted November 24, 2016 Any ideas who created these rules and why? I'm not trying to be provocative, I'm just curious because I see this inflexibility often repeated but rarely explained sufficiently. That's for example from Dr. Shelton, a fasting extremist who wrote one of the most extensive monographies (empirical, not scientific) on fasting, Definition of fasting: Fasting, as we employ the term, is voluntary and entire abstinence from all food except water. "Little driblet meals," says Dr. Chas. E. Page, "are not fasting. There should not be a mouthful or sip of anything but water, a few swallows of which would be taken from time to time, according to desire." We do not employ the word fasting to describe a diet of fruit juice, for example. Link to comment Share on other sites More sharing options...
mccoy Posted November 24, 2016 Report Share Posted November 24, 2016 By the way, I read Shelton's book many years ago and now, browsing the TOC, I realize that in the 30's, about 80 years ago, he wrote about autolysis, rejuvenation, growth and regeneration. The very same concepts today re-proposed and scientificlly analyzed by the recent specific literature, Longo and collaborators in particular. That's probably why I accepted almost instantaneously Longo's claims. Its rationale sounded all too familiar to me. By the way, apparently Gandhi used to consult Shelton's book before starting his public fasts. Was Dr Shelton a visionary? Partly so, partly he just drew from the ancient tradition of natural medicine, which had fasting as one of its main bulwarks. Link to comment Share on other sites More sharing options...
Mechanism Posted November 26, 2016 Author Report Share Posted November 26, 2016 Edited Link to comment Share on other sites More sharing options...
Mechanism Posted December 3, 2016 Author Report Share Posted December 3, 2016 Edited Link to comment Share on other sites More sharing options...
mccoy Posted December 3, 2016 Report Share Posted December 3, 2016 I realize that FMD is an option but with my temperament I prefer a shorter water only fast over a longer partial fast. Valter Longo feels duration in humans for benefits would be optimized at a minimum of 4-5 days, optimized at 5 ( source: http://joshmitteldorf.scienceblog.com/2014/06/12/the-three-day-fast-day-four/ ) hence the duration of 5 days. Some follow this diet but my low BMI I plan to do this no more than annually. Mechanism, the duration of FMD is exactly 5 days, so it would be equal to your planned 5 days water fast, not longer. I tend to have a fast metabolism (easy to loose, hard to gain weight) but sure not as fast as your impressively fast one. I lost 5 kg during a 5 days water only fast. I lost 2.5 kg during the recent 5 days FMD. I don't know how much you could expect to loose and I don't know how long it would take to regain weight. I'd say, proper refeeding and weight training should make the process pretty fast. Right now I didn't recover my previous weight after 12 days from the FMD. It would be easy if I could workout as much as I wished but some musculoskeletal aches are preventing me to do that. By the way, I wonder what such a fast metabolism actually implies. Very high basal energy expenditure? Or a catabolic-oriented metabolism? In the latter case that would mean that mTOR is inhibited most of the time. Pls let us know the outcome of your fast when it's the time, I'm curious. Link to comment Share on other sites More sharing options...
Mechanism Posted December 5, 2016 Author Report Share Posted December 5, 2016 Edited Link to comment Share on other sites More sharing options...
mccoy Posted December 6, 2016 Report Share Posted December 6, 2016 Mechanism, I read the interview you linked and unfortunately there is no reference on the date. It's pretty interesting anyway, it sounds like Longo experimented a semi-total fast of 4 days (tea, broth, bouillon with 200 cals max) and determined that "It is the minimum time required to switch to a full speed protective and fat burning profile that involved every single organ in the body: from the intestines to the brain." It's evident that it was not a water-only fast though, which is exactly zero calories. Then he talks about the 5-days FMD, evidently it was determined that one preliminary day of restricted intake was necessary to obtain the same benefits with about 750 cals a day mainly from vegetables. I can understand your excitement for the dietary adventure, since I experienced the same feeling when I started my first short fast, at the age of 14 . If you crave the spiritual experience then you should definitely go with a water-only fast. The whole digestive system gets a deserved rest. They usually do not advise fast to very thin individuals but you being a medical doctor are sure equipped with the decisional tools whether to go on or stop after one day. one whole day is very little but gives you a sample of the deprivation. I suggest you eat your evening meal then fast on water only the successive day, go to sleep on an empty stomach and then decide what to do (to keep on or to break the fast) on the successive day. I'm going to post my bodyweight temporal series, showing the sudden drop during the FMD and the gain during the reefeding. Right now I'm back at the initial weight, after about 15 days., eating according to hunger but always keeping proteins at about 10% of total calories. Link to comment Share on other sites More sharing options...
Sthira Posted December 6, 2016 Report Share Posted December 6, 2016 I'm always amazed that a freely available practice that for most people has virtually no side effects, loads of suggestive upside benefits, that is available to almost anyone, anywhere, anytime -- for no money, no clinical appointments or drama -- is so often relegated to the "spiritual." Spiritual! This really says a lot to me about the stronghold that the business of medicine has over people. If a pill or a device or a shot or indeed any med intervention were created that offers the benefits of not eating food for a few days or a week or so -- with nearly no side effects -- do ya think people might buy it? Haha... Personally I don't worry about being too skinny and having "a fast metabolism" because fasting isn't a weight loss method that works. The weight I lose fasting is purportedly "water weight" and after a few days post-fast refeeding this weight (according to my scale) comes right back. But if fasting makes you think about spiritual matters like god or Jesus or Allah, then that's great. That doesn't occur for me, but I'm glad for others! Link to comment Share on other sites More sharing options...
Mechanism Posted December 7, 2016 Author Report Share Posted December 7, 2016 Edited Link to comment Share on other sites More sharing options...
Sthira Posted December 7, 2016 Report Share Posted December 7, 2016 ...my largest meal is dinner and starting off with it fits well for the experiment....Do we know when is the best time to eat? The speculative answer is probably imbedded somewhere here at this site. Search tool, sthira, use the search tool. I think Dean might have it -- eat one meal per day early in the morning, then fast all day, all evening, through the night so the belly is empty during sleep. Maybe this feeding schedule shifts the body into daily sleep-like repair mode that extends past sleeping? If I eat a big meal at night, then isn't my body busy digesting as I sleep? Standing back: I don't even know if these are important questions to ask, nor if they matter. I'm bedrock speculating that all food causes damage, limit damage by limiting food, eat RDA-meeting nutrition. The same might hold for breathing. All breathing causes damage, slow breathing, slow damage. But the body also needs to eat, breathe, move, "exercise" and live a (happy) life. Sthira, i'm not 100% sure I understand your comments regarding the spiritual. Are you basically saying that why the need to justify a positive health intervention via other rationale?I think this is what I'm saying: why include "spiritual?" Fasting appears to extend health span (and maybe lifespan) in many creatures, including (maybe) primates. It also lowers body inflammatory, improves the adiponectin-leptin ratio, lowers insulin, IGF-1, maybe improves IGFBP-1,2, increases HGH...does many beneficial things no one yet understands precisely. I like Dr. Michael Klaper's influence: https://youtu.be/m92Y12lpl6Y But I'm compelled to stay quiet in my personal life about my fasting activities because immediately people assume it's about religion, spirituality, yoga, meditation. And I searched with the word "fasting" on the "news" function recently on google, and discovered that many evangelical christians were "praying and fasting" in hopes that Trump would be elected. Yuck. Want nothing to do with that motivation. In my case, although I suggested the possibility of a health benefit due to the high caloric intake I take by default, with my low BMI, the health benefits is far less clear than the general population. And the setting, I am using the word "spiritual", for something sort of existential that I do find inspiring. Just as with my triathlon, I find you can learn a lot about yourself via (reasonable, safe), pushing the envelope stretching yourself too abilities – not only a matter of resilience and grit, but also learning how you function in a sort of sense of meaning that can be imbued in overcoming obstacles in uncharted territory.Thank you, this describes me, too. Actually, I am not religious in the traditional sense myself ( though deeply concerned about creating goodness around me), and there was a time in my life when I was distrustful of the term "spiritual" due to various potential connotations... but I have over the years since adapted it in my own life to experiences and practices that I personally identify with meaning and purpose. Perhaps some extent these labels are internally defined ( within reason), because an experience or pursuit can mean so many different things to the eclectic people in this diverse and wondrous world. I would be interested in hearing more what ( aside from health motivations you mentioned) in broader terms fasting means to you... I think you brought up an interesting question.I think we're on the same page. My fasting motivation is mostly about maintaining health as best as I can until SENS-like therapies reach the masses. It's a long time away, we're told, and may never happen in our lifetimes. So I realize fasting and calorie restriction won't propel us into escape velocity -- but what choices have we got? It's all self-trailing in the face of unknown anti-aging biomarkers. If and when something better than fasting and CR comes along, I hope to drop my current behavior and adopt whatever is better. I think I was just commenting that even though you're very thin and have a fast metabolism and have difficulty gaining weight and maintaining muscle mass, fasting for a day or two doesn't "seem" to affect weight or induce more muscle wasting. And it may paradoxically do the opposite: for me I've grown stronger by fasting in ways I didn't while practicing 10-15% dietary restriction with an RDA-seeking diet. Link to comment Share on other sites More sharing options...
Mechanism Posted December 9, 2016 Author Report Share Posted December 9, 2016 Edited Link to comment Share on other sites More sharing options...
Michael R Posted December 9, 2016 Report Share Posted December 9, 2016 Fasting appears to extend health span (and maybe lifespan) in many creatures, including (maybe) primates. It also lowers body inflammatory, improves the adiponectin-leptin ratio, lowers insulin, IGF-1, maybe improves IGFBP-1,2, increases HGH...does many beneficial things no one yet understands precisely. To repeat my earlier thrust: fasting has been shown to extend health- and lifespan only to the extent that it concomitantly lowers Calories. It works as a CR protocol; it does not work on a net-balance energy basis. It does have some health benefits in the overweight, those with metabolic syndrome, etc, but (a) that isn't healthspan extension but avoidance of healthspan shortening, and (b) even those benefits are inconsistent from one human trial to the next, as documented elsewhere. I am not aware of any evidence that fasting is beneficial to nonhuman primates. I think I was just commenting that even though you're very thin and have a fast metabolism and have difficulty gaining weight and maintaining muscle mass, fasting for a day or two doesn't "seem" to affect weight or induce more muscle wasting. And it may paradoxically do the opposite: for me I've grown stronger by fasting in ways I didn't while practicing 10-15% dietary restriction with an RDA-seeking diet. Yes, but you're still relatively young and not undergoing a net reduction in Calories. I would personally be a bit concerned about supernumerary addition to to the gradual age-related loss of muscle mass, if not necessarily of quality. Yet the science gig -- attempting to understand and quantify fasting coupled with refeeding -- seems more like art. The science appears too difficult for scientists to accomplish, or maybe there's just not enough financial incentive or funding for scientists to get very far. It's been studied a fair deal — more than the underlying evidence base merits IMO. Link to comment Share on other sites More sharing options...
Sthira Posted December 11, 2016 Report Share Posted December 11, 2016 Fasting appears to extend health span (and maybe lifespan) in many creatures, including (maybe) primates. It also lowers body inflammatory, improves the adiponectin-leptin ratio, lowers insulin, IGF-1, maybe improves IGFBP-1,2, increases HGH...does many beneficial things no one yet understands precisely. To repeat my earlier thrust: fasting has been shown to extend health- and lifespan only to the extent that it concomitantly lowers Calories. It works as a CR protocol; it does not work on a net-balance energy basis. First, "Protocol" definition: "...4. : a detailed plan of a scientific or medical experiment, treatment, or procedure" Second, what does "net-balance energy basis" mean? If cronometer calculates reports that add my cumulative calories per week or per whatever -- per six months -- and those cumulative numbers reflect 20% calorie reduction, am I practicing CR? Do you define CR as only a chronic daily practice, or do other, wider definitions exist? Is periodic prolonged fasting -- if we're only calculating calories consumed -- a possible CR "protocol?" It [prolonged, regular fasting] does have some health benefits in the overweight, those with metabolic syndrome, etc, but (a) that isn't healthspan extension but avoidance of healthspan shortening, and (b) even those benefits are inconsistent from one human trial to the next, as documented elsewhere.So are you saying that fasting (>3 days) has benefits only to those who are overweight or those with metabolic syndrome? Are you saying that fasting has no benefits for healthy people? Regarding (a and b) can't we level the same comments at CR? Has CR been shown to not extend healthspan, but only to avoid healthspan shortening? Are CR's benefits consistent from one human trial to the next? Incidentally, where are the long term human CR peeps from yesteryear? If they're doing well or not doing so well, it'd be nice for us to know... If they're no longer stoked about posting here on this site, can we take that as meaning they didn't do so great on their CR journeys? I am not aware of any evidence that fasting is beneficial to nonhuman primates.Wait, so you've never watched your sick dog stop eating? I've no clear idea if widely-written observations of many species' behavior of "not eating" when injured or sick are true, partially true, or false -- and you're not aware. But I worked in a primate lab for a few years, and this was commonly accepted as true: when pan paniscus and pan trog felt down in the shits, they stopped eating. Parrot owners observe this, too. And my cat -- she pukes, then she wants no part of her organic, shade-grown, songbird-friendly cat kernals until she's (evidently) feelinmo betta. So fasting may be beneficial to not only humans, non-human primates, and other mammals, but also to insects, fungi, and plants. By "beneficial" I mean sickness and diseases. Aging is a disease, so all of us are diseased from birth to death. I think I was just commenting that even though you're very thin and have a fast metabolism and have difficulty gaining weight and maintaining muscle mass, fasting for a day or two doesn't "seem" to affect weight or induce more muscle wasting. And it may paradoxically do the opposite: for me I've grown stronger by fasting in ways I didn't while practicing 10-15% dietary restriction with an RDA-seeking diet. Yes, but you're still relatively young and not undergoing a net reduction in Calories. I would personally be a bit concerned about supernumerary addition to to the gradual age-related loss of muscle mass, if not necessarily of quality. Actually, according to cronometer reports, I do appear to be severely calorie reduced. By fasting I'm calorie reduced on a larger timeline than daily calorie reduced -- caveat if my own obsessive food weighing, eating docudrama is accurate, and cronometer is a useful tool. In fact, I'm reducing calories even more so now than I did yesteryear when I practiced daily calorie reduction. And yet what makes me doubtful that I am indeed "practicing CR -- despite the cronometer's cumulative calorie reports -- is that I weigh ten pounds more now than I did while daily CRing it. And today I'm much stronger and feel better (via fasting) than I did on CR. On CR, I felt like complete utter shit, and it was, back then, nearly Sisyphisian impossible to find enough energy to make an active living. Then again, I once bought your argument that CR is neither about weight nor BMI. CR is about calories consumed. So here I am now -- pursuing regular bouts of fasting, adding up to fewer weekly and monthly combined calories -- and yet I'm stronger now, and definitely more muscular and toned. Why would I cheat or lie? So: WTF? Yet the science gig -- attempting to understand and quantify fasting coupled with refeeding -- seems more like art. The science appears too difficult for scientists to accomplish, or maybe there's just not enough financial incentive or funding for scientists to get very far.It's been studied a fair deal — more than the underlying evidence base merits IMO.Yes, but mostly in mice, which aren't people. And the two macaque studies were all a-muddle. Meanwhile, I'm wondering if you think there's anything fun to the idea (Longo's most recently revived) that the benefits of fasting (>3 days) may be a two-part story: fasting tears down damage; refeeding rebuilds? Longo makes a dramatic statement during a Rhonda Patrick podcast that "not since birth" has post-fast refeeding demonstrated the profound rebuilding potentials to damaged body parts. Fung seems to be saying the same things -- that chronic CR is only part of the story. Prolonged fasting combined with refeeding iz the shiz -- it's the tear-down, build-up process (activate cellular destroy and repair programs) that may "slow aging." Do you disagree with this (not new) idea? Link to comment Share on other sites More sharing options...
Michael R Posted December 12, 2016 Report Share Posted December 12, 2016 First: Sthira, I seem to have pissed you off somehow, in which case I want to assure you that no offense was intended, and (as regards something you say below) I certainly didn't mean to imply you were in any way misrepresenting your experience. I'm just trying to keep us all straight on the science here. To repeat my earlier thrust: fasting has been shown to extend health- and lifespan only to the extent that it concomitantly lowers Calories. It works as a CR protocol; it does not work on a net-balance energy basis.First, "Protocol" definition: "...4. : a detailed plan of a scientific or medical experiment, treatment, or procedure"Second, what does "net-balance energy basis" mean?If cronometer calculates reports that add my cumulative calories per week or per whatever -- per six months -- and those cumulative numbers reflect 20% calorie reduction, am I practicing CR? Do you define CR as only a chronic daily practice, or do other, wider definitions exist?Is periodic prolonged fasting -- if we're only calculating calories consumed -- a possible CR "protocol?" Yes — exactly my point. In your scenario, If cronometer calculates that your cumulative calories per week reflect 20% calorie reduction, you have a fasting-based 20% CR protocol. As you're aware, there are a lot of people who are under the impression that intermittent fasting in particular can lead to the same benefits as CR despite no net reduction in Calories; rather, the studies show pretty clearly that it works to the extent that it lowers Calories — no more or less. It [prolonged, regular fasting] does have some health benefits in the overweight, those with metabolic syndrome, etc, but (a) that isn't healthspan extension but avoidance of healthspan shortening, and (b) even those benefits are inconsistent from one human trial to the next, as documented elsewhere.So are you saying that fasting (>3 days) has benefits only to those who are overweight or those with metabolic syndrome? Are you saying that fasting has no benefits for healthy people? ... if it has those, and beyond its effects as a CR protocol, yes. Regarding (a and b) can't we level the same comments at CR? Has CR been shown to not extend healthspan, but only to avoid healthspan shortening? No: CR very clearly extends life- and healthspan (as ever, in experimental animals: nothing has yet done either in humans for logistical reasons). Are CR's benefits consistent from one human trial to the next? The very few that have been done, yes; and the effects of reduced energy intake in the overweight and obese (not CR proper) are also broadly consistent on many but not all parameters, albeit with less impressive absolute outcomes. Incidentally, where are the long term human CR peeps from yesteryear? If they're doing well or not doing so well, it'd be nice for us to know... If they're no longer stoked about posting here on this site, can we take that as meaning they didn't do so great on their CR journeys? I don't think it means much of anything: most people get enthusiastic about CR early on, ask a lot of questions, figure out what works for them, and slowly lose interest in talking about it. There has also been splintering of the community into other fora, etc. I am not aware of any evidence that fasting is beneficial to nonhuman primates.Wait, so you've never watched your sick dog stop eating? My dog is not a nonhuman primate :P . IAC, we're in context again talking about a practice taken up intentionally as a chronic or periodic lifestyle practice for health- and lifespan extension in otherwise-healthy people, not treatment of existing pathology: cf. previous comments about metabolic syndrome (and Longo's preliminary but promising work on improving outcomes after cytotoxic chemo).Similarly, metformin is a great drug — for diabetics. But many people are wrongly imputing anti-aging properties to it. Etc. Actually, according to cronometer reports, I do appear to be severely calorie reduced. [...] And yet what makes me doubtful that I am indeed "practicing CR -- despite the cronometer's cumulative calorie reports -- is that I weigh ten pounds more now than I did while daily CRing it. And today I'm much stronger and feel better (via fasting) than I did on CR. On CR, I felt like complete utter shit, and it was, back then, nearly Sisyphisian impossible to find enough energy to make an active living. I do not take feeling like a lethargic lump of shit to be a good indicator of being on CR ;) . I, and a lot of other people on CR, feel wonderful on CR — just cold and occasionally rather hungry. A fasting protocol may just work better for you, in which case I'm doubly glad for you.To be clear, you were also using COM back in your regular-daily CR days, and comparing yourself to the same baseline now as then? (Ie, if you are now consuming 20% less than X baseline now, if you were Y% reduced on daily CR was thaat also in comparison to X, or some other baseline?) It does seem unlikely that you'd maintain a higher BW on similar net energy reduction over the long term. Then again, I once bought your argument that CR is neither about weight nor BMI. CR is about calories consumed. So here I am now -- pursuing regular bouts of fasting, adding up to fewer weekly and monthly combined calories -- and yet I'm stronger now, and definitely more muscular and toned. Why would I cheat or lie?So: WTF? I double your WTF. Did I imply you're cheating or lying? I don't have an issue with you fasting if you find it gives you some benefits, and if it's actually leading to CR I'm very happy for you. I just want to make sure that everyone is clear that as a practice for health- and lifespan extension in otherwise-healthy organisms, the evidence is clear that fasting works to the extent that it's a CR protocol and not to the extent that it doesn't. Meanwhile, I'm wondering if you think there's anything fun to the idea (Longo's most recently revived) that the benefits of fasting (>3 days) may be a two-part story: fasting tears down damage; refeeding rebuilds? Certainly it works in the narrow sense, but I don't believe there's any evidence (and find it biologically difficult to believe, once one is past one's twenties) that it either fully rebuilds, or rebuilds better than new. Remember, Longo's research context is for rebuilding the haematopoietic system in the context of cytotoxic chemotherapy, where the alternative isn't so good. Longo makes a dramatic statement during a Rhonda Patrick podcast that "not since birth" has post-fast refeeding demonstrated the profound rebuilding potentials to damaged body parts. "Body parts"? Is that a quote or close paraphrase? And he wasn't talking about the haematopoietic system? I mean, he wasn't talking about limb replacement, surely, or even recovery from chronic wasting disease — right? Can you point specifically to the recording and track point (many of RP's podcasts are also on YouTube and can be linked to specific timepoints, or whatever on her podcast platform)?I would be mildly surprised, but not shocked, to hear it had such effects following eg. trauma or burns, too — but, again, would find it much more surprising as a lifestyle practice in otherwise-healthy, non-injured people. Metabolism just normally doesn't work that way, and regenerative responses just get worse with age. Link to comment Share on other sites More sharing options...
Sthira Posted December 12, 2016 Report Share Posted December 12, 2016 First: Sthira, I seem to have pissed you off somehow, in which case I want to assure you that no offense was intended, and (as regards something you say below) I certainly didn't mean to imply you were in any way misrepresenting your experience. I'm just trying to keep us all straight on the science here. Yeek, golly no, I'm not angry at all -- just a crappy writer, I think. I'm also frustrated at the slow pace of the science here, and genuinely confused about why more isn't being accomplished in this realm. So perhaps some of my pissed offedness from impatience with why performing multiple >3-5 day fasts is just so hard. As you know, millions of us are underemployed and need more money. So if the excuse is "we can't find subjects" to perform multiple fasting studies, then I say use part of the grant money to pay people more to fast for >3-5d. This part upsets me, and indicates scientists just aren't motivated enough. ... As you're aware, there are a lot of people who are under the impression that intermittent fasting in particular can lead to the same benefits as CR despite no net reduction in Calories; rather, the studies show pretty clearly that it works to the extent that it lowers Calories — no more or less. I think one of Krista Varady's surprise findings that every other day feeding didn't induce people to eat much more on their non-fasting days. She says they expected to find that people would eat much more and even gorge like 70% more food upon refeeding, but this didn't happen. On refeeding days, people would eat only slightly more -- like 10% or so. Therefore, if we add up net calories, say, weekly or monthly, then wouldn't every other day (intermittent fasting) also be another CR protocol, and also be expected to deliver CR benefits? And this might also hold true for this 5:2 diet thing, and the "warrior diet" (where you eat only one meal per day, and let 24 hours pass before eating again)? If we add up honestly calculated calories in each of these dietary approaches, and find that they're all reducing calories, then wouldn't they also be examples of CR protocols? Regarding (a and b) can't we level the same comments at CR? Has CR been shown to not extend healthspan, but only to avoid healthspan shortening? No: CR very clearly extends life- and healthspan (as ever, in experimental animals: nothing has yet done either in humans for logistical reasons). Again, I just can't wrap my thick skull around why nothing much has been done in humans for logistical reasons. Goldhamer, Longo, Fung are all moving in this direction -- but why is it so hard to study people who fast on fasting retreats? People pay thousands of dollars to far-fling themselves into the jungles of self-inflicted starvation. Why not tap that energy? This negligence seems like something different is going on that's not mere ennui or disinterest. Are CR's benefits consistent from one human trial to the next? The very few that have been done, yes; and the effects of reduced energy intake in the overweight and obese (not CR proper) are also broadly consistent on many but not all parameters, albeit with less impressive absolute outcomes. So it may be this concept of "CR proper" that's hanging me up. What is that? If CR proper is one long lifespan of chronic daily calorie reduction from 21 years to death, then, yeah, totally unworkable. But what about studying CR improper and just looking at whatever biomarkers you feel most appropriate amongst the millions -- possibly billions -- of the world's fasting populations? Widen the definition of what CR means, and pay us more money for our participation, and I can find dozens of hippie acquaintances all around me to help progress this static science. A static science, mind you, that is for now our best current hope for extending life and-or healthspan. ...Longo's preliminary but promising work on improving outcomes after cytotoxic chemo).... ...Remember, Longo's research context is for rebuilding the haematopoietic system in the context of cytotoxic chemotherapy, where the alternative isn't so good. Longo makes a dramatic statement during a Rhonda Patrick podcast that "not since birth" has post-fast refeeding demonstrated the profound rebuilding potentials to damaged body parts. "Body parts"? Is that a quote or close paraphrase? And he wasn't talking about the haematopoietic system? I mean, he wasn't talking about limb replacement, surely, or even recovery from chronic wasting disease — right? Can you point specifically to the recording and track point (many of RP's podcasts are also on YouTube and can be linked to specific timepoints, or whatever on her podcast platform)? I would be mildly surprised, but not shocked, to hear it had such effects following eg. trauma or burns, too — but, again, would find it much more surprising as a lifestyle practice in otherwise-healthy, non-injured people. Metabolism just normally doesn't work that way, and regenerative responses just get worse with age. Listen to the first eight to ten minutes of this: https://youtu.be/d6PyyatqJSE Unless I'm misunderstanding him, he's talking about fasting (or his FMD, which is really just a way to generate more money for more research, IMO...) he's talking about fasting as a replacement for CR -- CR for everyone, he says, since daily chronic CR is too difficult for most people. Fast for five days a month, or every three months, six months -- depends upon the snowflake -- but fasting, he says sets programs into motion that CR does not. Fung is saying the same: kill cells through fasting, rebuild cells through refeeding. The primary benefits of fasting, as I understand what he's saying, don't come from just the fasting, or only the CR. The benefits are only completed by the refeeding. And I'm speculating that if I'm keeping accurate cronometer records, the reason I weigh ten pounds more, have more not less muscle strength, is because I'm allowing my body the opportunity to tear down damaged tissue and extraneous body metabolism junk, and then to rebuild it with a healthy plant based RDA-seeking diet that is, for me, 20% CR based on my metabolic rate. Either that, or I'm just inaccurately self-reporting the numbers into cronometer. Which, of course, is entirely possible. Meanwhile, I'd love to be a subject in a fasting study... boo hoo Link to comment Share on other sites More sharing options...
mccoy Posted December 12, 2016 Report Share Posted December 12, 2016 As far as I understood by reading Longo's book, he propounds the FMD fasting only twice a year for healthy and lean people. He advocates his FMD for various kinds of disorders up to once a month. His core message for healthy person is the longevity diet, a vegan+pescetarian diet where vegetables, fish appear only twice or thrice a week. In the Cheng et al. 2014, 'Cellpress' article, as far as I understood (which can be very little) Longo and his team contemplate HSC regeneration both with chemotherapy and without. Prolonged Fasting Cycles Regulate Stem Cells Independently of Chemotherapy and Help Reverse Immunosenescence ....Taken together, these results suggest that PF cycles can also stimulate the HSCs in a chemotherapy-independent manner, which leads to a lineage-balanced hematopoietic regeneration. Mimicking the Effects of Prolonged Fasting by Deficiency in GHR/IGF-1 Signaling Promotes Hematopoietic Recovery ... These data suggest that the periodically reduced IGF-1 signaling caused by PF cycles may play a crucial role in the hematopoietic regeneration observed in mice. Also, in the discussion part, PF versus CR is compared ...In mice, chronic calorie restriction (CR) promotes the self-renewal of intestinal stem cells, muscle stem cell engraftment and neural regeneration, preserves the long-term regenerative capacity of HSCs, and prevents the decline of HSC number during aging in certain mouse strains (Lee et al., 2002; Bondolfi et al., 2004; Cerletti et al., 2012; Chen et al., 2003; Ertl et al., 2008; Rafalski and Brunet, 2011; Yilmaz et al., 2012). Reduction of mTOR signaling has been implicated as one of the major molecular mechanisms responsible for the effects of CR on enhanced stem cell function (Huang et al., 2012; Rafalski and Brunet, 2011; Yilmaz et al., 2012). However, neither CR nor other dietary intervention had previously been shown to promote a coordinated effect leading to the regeneration and/or rejuvenation of a major portion of a system or organ. Because during PF mammalian organisms minimize energy expenditure in part by rapidly reducing the size of a wide range of tissues, organs, and cellular populations including blood cells, the reversal of this effect during refeeding represents one of the most potent strategies to regenerate the hematopoietic and possibly other systems and organs in a coordinated manner. Here, we show that PF causes a major reduction in WBC number, followed, during refeeding, by a coordinated process able to regenerate this immune system deficiency by changes beginning during the fasting period, which include a major increase in LT-HSC and ST-HSC and redirection of the frequency of Ly- HSC/Bala-HSC/My-HSC leading to a lineage-balanced mode. In fact, we show that PF alone causes a 28% decrease WBC number, which is fully reversed after refeeding (Figures 7B and S2F). Even after WBCs are severely suppressed or damaged as a consequence of chemotherapy or aging, cycles of PF are able to restore the normal WBC number and lineage balance, suggesting that the organism may be able to exploit its ability to regenerate the hematopoietic system after periods of starvation, independently of the cause of the deficiency (Figure 7B). In agreement with our results, starvation protects germline stem cells (GSCs) and extends reproductive longevity in C. elegans through an adaptive energy shift toward the less committed cells (Angelo and Van Gilst, 2009). In contrast, short-term fasting (%24 hr) in Drosophila promotes the differentiation of hematopoietic progenitors to mature blood cells (Shim et al., 2012). It will be important to determine whether the coordinated regenerative changes observed during PF and refeeding may resemble at least in part the sophisticated program responsible for the generation of the hematopoietic system during development. Recent studies revealed that HSCs rely heavily on the metabolic programs that prevent aerobic metabolism to maintain their quiescent state and self-renewal capacity (Ito et al., 2012; Takubo et al., 2013; Yu et al., 2013). In the case of PF, the energy metabolism is switched progressively from a carbohydratebased to a fat- and ketone body-based catabolism, which could The part I emphasized in the last text block seems to be the most important. The authors contend that PF (prolonged fasting) brings about regeneration and/or rejuvenation of a major portion of a system or organ. Link to comment Share on other sites More sharing options...
Sthira Posted December 13, 2016 Report Share Posted December 13, 2016 Grazie tanto per la traduzione del libro di Longo, il mio italiano è davvero di merda - una bella lingua del genere ... As far as I understood by reading Longo's book, he propounds the FMD fasting only twice a year for healthy and lean people. Does he explain why for healthy and lean people why only twice per year? Anyone please correct me if I'm wrong, but do the explanations stretch beyond potential malnourishment, dizzy-headedness, weakness and discomfort? Don't crash la bicicletta because you've not eaten for four days? He advocates his FMD for various kinds of disorders up to once a month. His core message for healthy person is the longevity diet, a vegan+pescetarian diet where vegetables, fish appear only twice or thrice a week. I have no disorders (yet); aging into disease and then death are all of our futures, though, and so I'm pushing the fasting bit myself beyond moderation -- because wtf I'm not getting out of here alive anyway, why not attempt pioneering like our ancestors pushing into immoderate unknowns despite the frowns and finger wags of conservatives? By that I mean I'm fasting water only a lot -- molto stupido io -- but here's what happens (in case you care): I wake up one day and say, today I'll fast, and when I feel crappy, I'll stop and refeed. What happens when I don't feel bad is I just keep going, stretching out the fast, highs and lows, one day to two to three e ancora domani... How much of this "stressing the system" as Longo says, drifts into unhealth? On one hand Longo says "not eating" is "more common" historically for us than eating; but these were days of involuntarily starvation due to bad times and lack of convenient calories, or bad harvests, bad luck... But today we're very lucky and we may choose for ourselves when to eat and when not to eat. We may choose for ourselves to eat as healthy as possible, or not. We may choose for ourselves when to turn on the body's Program-One: fasting = system protection, and when to choose the body's Program-Two: refeeding=system regeneration. But we're left with how much is too much and not enough "for healthy lean" people only seeking to extend healthy leanness? Or, Momma Madona, dreams of "lifespan extension?" In the Cheng et al. 2014, 'Cellpress' article, as far as I understood (which can be very little) Longo and his team contemplate HSC regeneration both with chemotherapy and without. Prolonged Fasting Cycles Regulate Stem Cells Independently of Chemotherapy and Help Reverse Immunosenescence ....Taken together, these results suggest that PF cycles can also stimulate the HSCs in a chemotherapy-independent manner, which leads to a lineage-balanced hematopoietic regeneration. Aren't we told that we in the healthy tribes gazing up at the night sky have probably "millions of dormant cancer cells?" All of us no matter what we do? If that's true and cancer is simply waiting behind the curtains for everyone everywhere -- eventually -- then why not start now to autophagy-away some of these deadly cells we're all growing? Even though we don't have cancer yet, eventually we will. Fast today for tomorrow's health? The yoga community has a phrase for this: practice today to slow the (aging) diseases of tomorrow. The authors contend that PF (prolonged fasting) brings about regeneration and/or rejuvenation of a major portion of a system or organ. So how often we do it remains personal until technology in this realm advances to the "personalized medicine"? Are we back to waiting for artificial medical intelligence? Link to comment Share on other sites More sharing options...
Mechanism Posted December 13, 2016 Author Report Share Posted December 13, 2016 Edited Link to comment Share on other sites More sharing options...
Sthira Posted December 13, 2016 Report Share Posted December 13, 2016 ^ Mechanism: With great numbers like that, wouldn't you tell one of your patients with similar numbers to keep doing what you're doing? This is what my doctor says to me anyway, and, she says, "...don't push too hard and injure yourself, and furthermore, no, I'm not prescribing rapamycin and metformin for you because that's a crazy idea and there isn't enough evidence..." "But how about very low doses? Like 6mg per week, and the metformin as a counter against possible sugar problems?" "No." Haha, and then I sulk and go on a fasting strike for the poor conditions of earth's creatures. ...family susceptibility towards aggressive cancer. This would be my reason to experiment with fasting. At least according to my extrapolation of Longo, I want to kick out dormant cancer cells before they raise their stupid sugar and amino acid loving heads. "Cancer cells are stupid," Longo says, and when you don't provide them nourishment, they may not survive the starvation. Three day fasts for cancer patients undergoing chemotherapy helps healthy cells survive the chemo while killing some of the cancer cells. If this works for cancer patients, then would it work for us, too, and for you, since: ...family susceptibility towards aggressive cancer. Michael, I think I am following your objection for the general population with potentially limited benefit aside from impact on overall caloric intake... Keep in mind that Michael is 6 feet tall and weighs 115 pounds. So he's not the general population, you're not the general population, and I'm clearly a freak. ...while most biomarkers look good, and the BMI is certainly very low, but this does not mean that this high caloric intake individual ever "cleans house" / autophagy. A CBC can be one measure of autophagy and these look normal ( not CR) at WBC of 5.7 and H&H of 14.8/44.2. Who knows for other measures of autophagy. During prolonged fasting, white blood cells apparently diminish. Upon refeeding (even amongst unhealthy folk) those cells evidently dance back into duty. Are there any ways to measure how many cancer cells are now waiting within our bodies? With trillions of cells, and millions are probably cancerous, how would better medical devices be designed to give us more hints? ... how do you feel about an ( only once annually given low BMI ) 3-5 day FMD or water fasting prococol as insurance that some autophagy is occurring in this high caloric intake individual? Other comments / reflections on this unique case study also appreciated. We're stuck with no operating manual with instructions on how to navigate these wildly complicated organisms across time and space. Until then....? Link to comment Share on other sites More sharing options...
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