Guest Max Posted February 9, 2015 Report Share Posted February 9, 2015 Hi, everyone, reading some recent books and papers I've gathered some clues that not caloric restriction in general but the blood sugar control/insulin control might be the major cornerstone for longevity - so I wonder if low-carb, low-glycemic (but fructose-limited) oder even low-carb high-fat (good fats like Omega-3 rich plant oils) diets could give the same fine results like caloric restriction. Is there any recent reseach available focussing this issue? Any ideas/hints or publications are much appreciated! Thanks! Max Link to comment Share on other sites More sharing options...
timc Posted February 11, 2015 Report Share Posted February 11, 2015 I'm reminded of this post from years ago, though I don't think it answers your question: arc.crsociety.org/read.php?2,115719,115719#msg-115719 You didn't say whether you're trying to keep rats or humans alive and that might make a difference. With rodents, the answer is less ambiguous. It is the calories. Works for dogs: www.sciencedaily.com/releases/2007/04/070419160140.htm Here are contradictory results from rhesus monkee studies: www.sciencedaily.com/releases/2014/04/140401111957.htm www.nature.com/nature/journal/v489/n7415/full/nature11432.html The postive results are: The Wisconsin scientists began to see diabetes among the control animals while they were still in the prime of life, within six months after beginning their study. The contrast with the restricted animals could not have been more dramatic, Colman says. "Until two years ago, we did not have evidence of diabetes in any caloric-restriction animal, but we had a significant numbers of diabetes, or pre-diabetes, metabolic syndrome, in the control animals." www.sciencedaily.com/releases/2014/04/140401111957.htm So avoiding a diabetic or even prediabetic state seems crucial. Link to comment Share on other sites More sharing options...
Michael R Posted February 11, 2015 Report Share Posted February 11, 2015 @Guest_Max (my old friend Max by any chance, or new intenet acquaintance Max?), First, welcome to the CR Society Forum! Please do me and you and everyone on the Forum a favor: register on the Forums and log in each time before you post! It's fine if you want to use a pseudonym, but registering and logging in will ensure that you can't be impersonated and will make it easier to keep track of your questions, input, and progress. As to your question: I've actually been slowly working on a detailed reply, so please check back in — but I wanted to respond more immediately to some of Tim's comments: I'm reminded of this post from years ago, though I don't think it answers your question:arc.crsociety.org/read.php?2,115719,115719#msg-115719 (The Archives are down at the moment, so I can't comment on this ...). With rodents, the answer is less ambiguous. It is the calories. Works for dogs:www.sciencedaily.com/releases/2007/04/070419160140.htm That study shows you that CR works in dogs; it doesn't tell you whether glucoregulation is important to the effect, or whether it is both necessary and sufficient independent of energy intake, or whether it's all about the carbs, which are Max's questions. Here are contradictory results from rhesus monkee studies:www.sciencedaily.com/releases/2014/04/140401111957.htmwww.nature.com/nature/journal/v489/n7415/full/nature11432.html You might mean here that the two monkey studies are contradictory to each other (which they at least seem to be on the key question of lifespan), but I assume in context that you think that they somehow impact Max's questions, which I don't think they do (see commments on dog study above). (More on the seemingly-opposing outcomes of the two monkey CR studies here). Link to comment Share on other sites More sharing options...
Guest Max Posted February 14, 2015 Report Share Posted February 14, 2015 Hi, MichaelR, thanks for the warm welcome! I'd love to register here but I'm in trouble since I need to become member of the CR Society...I hope you folks don't mind if I choose to first make up my mind before doing so; my financial possibilities are quite limited at this time of the year. And nope, I guess, I'm a "new" Max - I haven't been posting here before but I love your work and those archives. I'm reading Gary Taubes "Good calories Bad calories" right now and think, this book is an eye-opener! I'm on a personal "reshape-myself" trip for two years now; trying several fasting/diet concepts to improve my health and lose weight. I've got quite far, I guess and since I've made great progress using low-Carb-approaches, this book just fit in. Thanks for the swift reply and all those studies. I guess the first "human" results will come frome Sweden where LCHF is quite popular. But since this needs a long-lasting commitment of a reasonable number of peeople it may take some time and maybe be diluted by other epidemiological effects. There are severel trials demonstrating a general improvement of health and weight under lowCarb regimes in human but since they're limited in time and often caloric reestriction it's hard to tell which parameter "to blame" for the improvements...loosing weight? Caloric restriction? Carb restriction? Or everything of all? Under http://www.nejm.org/doi/full/10.1056/NEJMoa022637 and http://diabetes.diabetesjournals.org/content/41/10/1278.short and http://ajcn.nutrition.org/content/77/1/43.short and http://www.metabolismjournal.com/article/0026-0495%2892%2990111-M/abstract are some trials demonstrating the improvements of several blood markers in different human groups under LCHF regimes comared to high-carb diets. A nice analysis of 23 human trials can be found here: http://authoritynutrition.com/23-studies-on-low-carb-and-low-fat-diets/ Anyway; nothing so far regarding longevity... Max Link to comment Share on other sites More sharing options...
Michael R Posted February 15, 2015 Report Share Posted February 15, 2015 Just a quick note for now: Hi, MichaelR, thanks for the warm welcome! I'd love to register here but I'm in trouble since I need to become member of the CR Society...I hope you folks don't mind if I choose to first make up my mind before doing so; my financial possibilities are quite limited at this time of the year. I don't believe you need to be a member to register, although you get access to more functions if you are: you just need a valid email and to be sufficiently human in your ability to recognize a Captcha. Link to comment Share on other sites More sharing options...
Guest Max Posted February 15, 2015 Report Share Posted February 15, 2015 Hmm, I might not find the right key to hit - but I just see a "sign in"-button in the upper corner on the right. If I use it, it leads me to "create an account" and there I have to pick between three different types of membership. I haven't found an exclusive "Forum sign-in" button so far... Best regards Max Link to comment Share on other sites More sharing options...
timc Posted February 15, 2015 Report Share Posted February 15, 2015 Hi Max, Just click the "Create Account" button (or this link) and then click the Create Account button again without checking any box. Link to comment Share on other sites More sharing options...
Max Posted February 15, 2015 Report Share Posted February 15, 2015 Ah, o.k., thanks - this has worked!! Great! Max Link to comment Share on other sites More sharing options...
Michael R Posted February 21, 2015 Report Share Posted February 21, 2015 Max, sorry to keep you waiting on this: I got much of the way through a reply, and then stalled out with a significant amount of work to be done. Rather than leave this in limbo indefinitely, I'm going to post what I had gotten through when I got waylaid, and then BRIEFLY summarize points I would have backed up with better evidence had I had more time to dedicate to the question. As an overarching point, you have to be really careful when reading studies about the effects of insulin sensitivity and blood sugar on long-term health (and especially media and blog accounts of those studies), because often when they say that they are comparing people with "low" insulin or blood sugar levels, or "high" insulin sensitivity, to the converse, what they are really doing when you dig into it is comparing people with normal levels to people with clearly unhealthy levels (prediabetic or outright diabetic). While of course having abnormally high insulin and blood sugar is bad for you, it is then implied that it is therefore best to have exceptionally low levels of insulin or glucose. But this idea really hasn't been borne out by studies actually and directly assessing the effects of exceptionally low levels of insulin or glucose to merely normal levels, nor that these values are critical to the effects of CR. Notably, in (1), researchers engineered mice to express more of the insulin-responsive glucose transporter GLUT4, so that they would rapidly lower their blood sugar in response to a meal. They then fed these animals either AL or 40% CR. This substantially lowered their average 24-hour plasma insulin levels: NTGA = nontransgenic mice fed ad libitum; NTGR = nontransgenic mice fed 40% less than ad libitum; TGA = transgenic mice fed ad libitum; TGR = transgenic mice fed 40% less than ad libitum. *Significantly less than NTGA mice (p <.05). **Significantly less than all other groups of mice at given age (p <.05) ... and glucose levels: Note that the values for the TransGenic Ad lib group's blood sugar and insulin levels were substantially improved; while not quite as good as the Non-TransGenic Calorie Restricted group's, the CR group was on full-on 40% restriction, which is quite a severe r level that no free-living human can sustain, so getting levels that low is moot anyway. In any case, lowering glucose and insulin levels had no effect on tissue pathologies or diseases of aging in any group — not AL, and not CR: (See their Table 1 and references 18 through 20 for the full list of pathologies they looked for: tumors, kidney disease, cardiac pathology, and much else). Nor did it affect any group's lifespan, except maybe maybe maybe for a slight decrease in mortality in the AL group between 21 and 27 months (ie, early seniority ages): Whatever the mechanism(s) of CR, then, you can't achieve them just by lowering glucose and insulin levels — nor can you improve them by pushing these levels even lower than is achieved in severe CR. In a separate and even more surprising study, engineering mice to have very high insulin sensitivity was actually harmful to lifespan, and very slight insensitivity was actually beneficial: Quote Interference in insulin and/or insulin-like growth factor 1 (IGF-1) signaling can extend invertebrate life span ([oundworms and fruit flies -MR], and interference in IGF-1 signaling can extend murine life span. Whether interference with murine insulin signaling, which can be diabetogenic and pathological, is also life-extending is controversial. We therefore measured life span in 3 murine strains genetically modified to reduce or increase insulin sensitivity. Mice with reduced insulin sensitivity were hemizygous for a null mutation in the insulin receptor (insulin receptor knockout mice; IRKO+/−). Mice with increased insulin sensitivity either had a null mutation of protein tyrosine phosphatase 1B (PTP-1B−/−) [which counteracts the intercellular signaling of insulin -MR] or overexpressed peroxisome proliferator-activated receptor-α coactivator (PGC)-1α (PGC-1αTG) . Life span of insulin insensitive IRKO+/ mice was increased (males) or unaffected (females). Life spans of mice with increased insulin sensitivity were shortened overall (PTP-1B−/− mice) or partially (PGC-1αTG: survival at the 25th percentile was reduced). These results show that insulin sensitivity in some murine genotypes is inversely related to longevity and provide further evidence for evolutionary conservation of this pathway as a modulator of longevity.(2) On top of this, the usual understanding of the effects of CR on glucose metabolism is overly simplistic. CR leads to low-to-normal fasting glucose, and very low fasting insulin — but surprisingly, Calorie restriction leads to some level of glucose intolerance (meaning, high blood sugar after a meal) in mice, monkeys, and men. This doesn't appear to be insulin insensitivity: the tissues of CR mice are very insulin sensitive (and they preserve that sensitivity with age as it deteriorates in AL animals), and from indirect measurements it appears that even glucose-intolerant CR humans are also quite insulin sensitive — yet give them an oral glucose tolerace test, and it takes them longer to restore normal glucose levels. This may be due to an insufficient or delayed production of insulin by pancreatic beta-cells in response to incoming blood sugar, and/or due to the lack of tissue to soak up that glucose. Whatever the cause, it shows pretty clearly that consistently low glucose is not necessary for the anti-aging effects of CR (and, again, (1) shows it isn't sufficient, either). Similarly, two of the very few lifespan-extending interventions that really work (and that have related mechanisms to those of CR) also lead to impaired rather than improved glucose tolerance — namely, rapamycin and several different kinds of dampening down of IGF-1 signaling (adult onset-isolated GH deficiency (AOiGHD); and some paradoxical effects (THERE SHOULD BE DETAILS HERE -- SORRY!) in Ames dwarves and growth hormone receptor knockout (GHRKO/GHR-/-) mice). Consistent with this, it's exactly the most metabolically CRed subset of human CR practitioners (as assessed by an index based on IGF-1, T3, and testosterone) in which impaired glucose tolerance manifests: Response to an oral glucose tolerance test in the overall calorie-restricted (CR) group (black circle), the exercise (EX) group (open circle), and the Western diet (WD) group (black triangle). Baseline values were significantly different between groups for glucose, insulin, and C-peptide (ANOVA). *P ≤ 0.05, significantly different from WD group (Tukey’s tests). **P ≤ 0.05, significantly different from EX group (Tukey’s tests). †P ≤ 0.05, significantly different from CR group (Tukey’s tests). Reproduced from (5). Calorie restricted normal glucose tolerance (CR-NGT) subgroup (black circle) and the calorie restricted impaired glucose tolerance (CR-IGT) subgroup (open circle). *P ≤ 0.05, significantly different from CR-IGT subgroup (Student t test). Reproduced from (5). In fact, although metabolic syndrome and diabetes are clearly bad for one in all kinds of ways, in the human population studies, results have come in all over the map as to whether low-normal, very low, or even high-normal glucose/HbA1c is best for longevity. It appears to me that the healthiest FASTING glucose in nondiabetic men seems to be somewhere in the 75-85 mg/dL range, but this really isn't resolved. On your (Max's) idea of low-carb diets per se as a way to achieve this: first, if you look at the various studies of low-carb diets, (a) in most cases the benefits are attributable to weight loss per se and not to macronutrient ratios; ( B) the levels achieved really only put you in the 'normal' range for glucose and fasting insulin, not some extra-low level, and are mostly restricted to people with initial diabetes or prediabetes. (Sorry: no time to document). Of course, as argued above, it's not at all clear that you would want to go any lower. Additionally, CR studies have at different times compared the effects of different carb sources and levels of carb, fat, and protein, and (leaving aside a somewhat tricky question around protein), very low-carb diets have failed to have any meaningful effect separate from Calorie intake. (Sorry: no time to document). I certainly think that added sugar (in all forms, including "organic cane extract," maple syrup, sucarat, blackstrap molasses, concentrated fruit juices, and especially agave) is a Bad Thing, and I think it's sensible to eat a low-GI, low-GL diet, but not to get as fanatical about it (and I mean that in a friendly way, as a notorious fanatic myself). References 1: McCarter R, Mejia W, Ikeno Y, Monnier V, Kewitt K, Gibbs M, McMahan A, Strong R. Plasma glucose and the action of calorie restriction on aging. J Gerontol A Biol Sci Med Sci. 2007 Oct;62(10):1059-70. PubMed PMID: 17921417. 2: Nelson JF, Strong R, Bokov A, Diaz V, Ward W. Probing the relationship between insulin sensitivity and longevity using genetically modified mice. J Gerontol A Biol Sci Med Sci. 2012 Dec;67(12):1332-8. doi: 10.1093/gerona/gls199. Epub 2012 Oct 22. PubMed PMID: 23089336; PubMed Central PMCID: PMC3670160. 5: Fontana L, Klein S, Holloszy JO. Effects of long-term calorie restriction and endurance exercise on glucose tolerance, insulin action, and adipokine production. Age (Dordr). 2009 Nov 11. [Epub ahead of print] PubMed PMID: 19904628. Link to comment Share on other sites More sharing options...
Robert Cavanaugh Posted February 22, 2015 Report Share Posted February 22, 2015 Excellent work, as usual, Michael. Link to comment Share on other sites More sharing options...
Max Posted February 23, 2015 Report Share Posted February 23, 2015 Hi, MichaelR, first of all thanks a lot for digging so much into this...must have taken a lot of time which is hard to find nowadays! I see your point; I just have hard to nibble on this calory-concept. The more I'm working myself into this the more I got convinced, that a calorie is not a calorie. Taking "just" calories to explain those effects of CR is a too simplistic way in my opinion but I fail to provide a better one to access ths phenomenon. I'm on a LCHF-diet now for a while and it's interesting to learn that "overeating" doesn't occour anymore; at least I need carbs to "overeat". I stick somewhere between 80 and 98% of my calculated "daily need". But on the other hand I had to learn that for achieving my weight goal (still a BMI of 28...even though muscular) I need to skip the fasting (just 600-800 kcal every 2nd day); otherwise my weight loss was stalling despite an impressive caloric deficit. I also got the feeling by reading a lot of ressources, that the energy metabolism is a very sensible machanism which gets easily disturbed by enforced restriction and forces the body to cut back...which leaves me wondering if CR is still CR if it fits to the current need of the body. But maybe it's a personal issue; I'm suffering from a heterzygous FH and Hypothyroidism so my case might be hard to compare with others. Thanks again for you work on this!!! Max Link to comment Share on other sites More sharing options...
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