Dean Pomerleau Posted November 25, 2015 Report Share Posted November 25, 2015 On the thread about cranberries, Rodney got us talking about prunes, and how they may be good for maintaining bone health via increased IGF-1, which is a double-edged sword. This is pretty well-known among knowledgeable CR practitioners, but I thought it worth highlighting, particularly since I came across this interesting discussion & video on the potential tradeoff between "performance" and longevity with respect to IGF-1. It discusses (and gives citations) for many of the benefits of IGF-1, including muscle repair/preservation as well as long-term cognitive health. Interestingly, it doesn't mention helping maintain bone health as another benefit of the anabolic effects of IGF-1. But on the downside, it talks about increased cancer risk and the widely-observed reduced longevity (in humans and animals) associated with higher levels of IGF-1. Here is the summary paragraph: There you have it. It’s a trade-off when it comes to growth hormone and IGF-1. More of it enhances muscle and neuronal growth while simultaneously preventing atrophy. Less of it will increase the expression of stress resistance genes and extend your lifespan. Which do you prefer, having better muscle and cognitive performance or living longer? Overall, it seems like a good primer for anyone who wants to learn about the pros and cons of the reduced IGF-1 often associated with practicing CR. --Dean Link to comment Share on other sites More sharing options...
Brett Black Posted November 28, 2015 Report Share Posted November 28, 2015 There is no clear evidence of longevity benefits of lower IGF-1 in humans, the current evidence is contradictory. Laron dwarfism in humans, which results in congenitally low IGF-1 (and which resembles the longevous genetically-modifed IGF-1 deficient rodent models) has not been observed to result in unusually long lives. Among other things, lower IGF-1 may reduce risk of cancer mortality, and since many(most?) common laboratory mice strains have high mortality due to cancer (think 90%) this may largely explain the benefit seen in mice. However, lower IGF-1 may, among other things, increase risk of mortality from cardiovascular diseases, and whilst cardiovascular mortality is not a significant threat in mice, it is in humans. Basically, the benefits and detriments of higher or lower IGF-1 may be species, strain and disease specific. There is also evidence that the lifespan benefits seen in mice from lower IGF-1/GH may only be realized when they are kept low during early life (equivalent perhaps to the childhood/adolescent years in humans.) Some of the issues reported by and personally concerning calorie restriction practitioners (e.g. bone health, impaired glucose tolerance) might benefit from increased IGF-1. Just generally IGF-1 and its anabolic growth and repair-inducing effects may oppose many of the common and serious quality-of-life problems associated with aging including cognitive decline, muscle wasting, cardiovascular dysfunction, skin aging etc and I think it is something that should be considered very carefully. Dean (and anyone else interested), I can't recommend highly enough reading the first paper I have linked to below. It contains a wealth of very interesting and potentially important information regarding IGF-1 and its relation to lifespan, healthspan and disease in both humans and rodents. "Diverse Roles of Growth Hormone and Insulin-Like Growth Factor-1 in Mammalian Aging: Progress and Controversies" http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348498/ "Recent landmark studies from Panici et al. indicate that administration of GH from day 14 for 6 weeks to the long-lived Ames dwarf animal completely reversed the increased life span in these animals. Finally, studies from the Jackson Laboratory comparing over 30 strains of mice indicated that IGF-1 levels at 6 months of age are inversely correlated with life span and that this correlation decreases as animals age. By 18 months of age, the correlation is essentially lost, suggesting that only levels of circulating IGF-1 earlier during the life span are predictive of life span." "Based on the literature, GH and IGF-1 have both beneficial and deleterious effects on specific pathologies that undoubtedly influence life span. Therefore, in many cases, the consequences of GH and IGF-1 deficiency are dependent on the species, background strain, and pathologies that the species or strain is susceptible. Those animals that are at risk for cancer, liver, or kidney disease will likely exhibit a shortened life span in response to elevated levels of GH and IGF-1, and we expect that those animals with reduced risk for these diseases will likely not exhibit increased life span in response to this intervention. Similarly, those species at risk for specific cardiovascular diseases (stroke, myocardial infarction, heart failure, vascular cognitive impairment) may benefit from elevated levels of these hormones. These effects are consistent with the classical actions of GH and IGF-1 being important anabolic agents that stimulate cell growth, proliferation, and tissue repair. Because cardiovascular diseases, metabolic diseases, and cancer are all important health issues in the elderly population, the effects of GH/IGF-1 pathway on human health span and life span are predictably complex." --- "Low circulating IGF-I bioactivity is associated with human longevity: Findings in centenarians' offspring" http://www.impactaging.com/papers/v4/n9/full/100484.html "Data on IGF-I system in relation to longevity are still controversial. Bonafè et al. [9] previously found that subjects with at least an A allele of the IGF-I receptor (IGF-IR) gene (G/A, codon 1013) had low levels of free plasma IGF-I and were more represented among long-lived people. In contrast, Paolisso et al. [10] found an increased plasma IGF-I/IGF binding protein 3 (IGFBP-3) molar ratio in healthy centenarians compared to aged subjects. They suggested that this elevated ratio reflected higher IGF-I bioavailability which contributed to the observed improved insulin action in centenarians. An overrepresentation of heterozygous mutations in the IGF-IR gene associated with high serum IGF-I levels and reduced activity of the IGF-IR has been reported in Ashkenazi Jewish centenarians compared to controls [11]. In addition, in humans positive associations between circulating total IGF-I levels and cancer mortality have been found in many studies [12-14], while low total IGF-I levels have been associated with an increased risk for cardiovascular diseases and diabetes [15-22]. On the other hand, Rozing et al. showed that offspring of familial nonagenarians displayed similar IGF-I and IGFBP-3 levels compared to their partners [23]. These conflicting results probably reflect the complexity of the IGF-system." --- "Functionally significant insulin-like growth factor I receptor mutations in centenarians" http://www.pnas.org/content/105/9/3438.full "Here, we studied the biochemical, phenotypic, and genetic variations in a cohort of Ashkenazi Jewish centenarians, their offspring, and offspring-matched controls and demonstrated a gender-specific increase in serum IGFI associated with a smaller stature in female offspring of centenarians. Sequence analysis of the IGF1 and IGF1 receptor (IGF1R) genes of female centenarians showed overrepresentation of heterozygous mutations in the IGF1R gene among centenarians relative to controls that are associated with high serum IGFI levels and reduced activity of the IGFIR as measured in transformed lymphocytes." --- 1. Horm Res. 2004;62 Suppl 1:101-7. Insulin-like growth factor I and impaired glucose tolerance. Dunger D(1), Yuen K, Ong K. Author information: (1)University Department of Paediatrics, University of Cambridge, Cambridge, UK. dbd25@cam.ac.uk The effects of circulating insulin-like growth factor I (IGF-I) on glucose metabolism are well recognized. IGF-I is also important in maintaining beta-cell mass and regulating endogenous growth hormone (GH) levels. Low IGF-I levels could explain links between small birth size and the risk of developing type 2 diabetes mellitus in short, obese adults. In a recent prospective study, childhood insulin secretion was related to IGF-I levels and statural growth, whereas insulin sensitivity was related to early post-natal weight gain. Common genetic polymorphisms in the IGF1 gene have been linked to small birth size, post-natal growth and future diabetes risk, but these results have been inconsistent. Recent adult studies have demonstrated that lower baseline IGF-I levels predict the subsequent development of impaired glucose tolerance (IGT), type 2 diabetes and cardiovascular disease. Administration of low-dose GH therapy, at a dose that minimizes the lipolytic effects of GH and has the ability to increase IGF-I levels, enhances insulin sensitivity in young healthy adults and in GH-deficient adults and increases insulin secretion in individuals with IGT. Whether the administration of low-dose GH, recombinant IGF-I or combined IGF-I/IGF-binding protein 3 therapy prevents future development of IGT or type 2 diabetes in high-risk normoglycaemic and GH-deficient individuals merits further long-term studies. Copyright 2004 S. Karger AG, Basel. PMID: 15761241 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/15761241 Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted November 28, 2015 Author Report Share Posted November 28, 2015 Brett, Thanks for the pointers. The first link you sent and urged us to read, review [1], talks mostly about the tradeoff between increased cancer risk with high IGF-1 and increased heart disease risk with low IGF-1. Given the choice between the two, I consider myself more likely to die from cancer than from heart disease given my risk factors, so I'd rather err on the side of low IGF-1. I think many other CR practitioners are likely in the same boat, with very low risk of CVD. There is no clear evidence of longevity benefits of lower IGF-1 in humans... It seems to me that the studies of Ashkenazi Jewish centenarians (AJC), and especially their offspring [2] who are younger and therefore easier to compare with age-matched controls, pretty clearly point to the importance of IGF-1 in human longevity, and more specifically, reduced IGF-1 signalling. It may be a little controversial whether this is accomplished in the AJC and their offspring by lower circulating IGF-1 directly or higher IGF-1 binding to make it less bioavailable, or both. But the message is clear, lower IGF-1 signalling in humans is associated with increased longevity, as it is in most animal models tested. Regarding insulin sensitivity and diabetes, long-term CR practitioners appear a lot like the AJC, with low fasting insulin and high insulin sensitivity. Overall it still seems to me that the title of this thread remains accurate - the evidence suggests there is a tradeoff between the likely longevity benefits of low IGF-1 (or IGF-1 bioavailability) on the one hand and the benefits of the anabolic effects of higher IGF-1 on the cardiovascular system, the brain and skeletal muscles. --Dean -------------- [1] J Gerontol A Biol Sci Med Sci. 2012 Jun;67(6):587-98. doi: 10.1093/gerona/gls115. Epub 2012 Apr 20.Diverse roles of growth hormone and insulin-like growth factor-1 in mammalianaging: progress and controversies.Sonntag WE(1), Csiszar A, deCabo R, Ferrucci L, Ungvari Z.free full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348498/Because the initial reports demonstrating that circulating growth hormone andinsulin-like growth factor-1 decrease with age in laboratory animals and humans,there have been numerous studies related to the importance of these hormones forhealthy aging. Nevertheless, the role of these potent anabolic hormones in thegenesis of the aging phenotype remains controversial. In this chapter, we reviewthe studies demonstrating the beneficial and deleterious effects of growthhormone and insulin-like growth factor-1 deficiency and explore their effects onspecific tissues and pathology as well as their potentially unique effects earlyduring development. Based on this review, we conclude that the perceivedcontradictory roles of growth hormone and insulin-like growth factor-1 in thegenesis of the aging phenotype should not be interpreted as a controversy onwhether growth hormone or insulin-like growth factor-1 increases or decreaseslife span but rather as an opportunity to explore the complex roles of thesehormones during specific stages of the life span.PMCID: PMC3348498PMID: 22522510 ----- [2] Aging (Albany NY). 2012 Sep;4(9):580-9. Low circulating IGF-I bioactivity is associated with human longevity: findings incentenarians' offspring.Vitale G(1), Brugts MP, Ogliari G, Castaldi D, Fatti LM, Varewijck AJ, LambertsSW, Monti D, Bucci L, Cevenini E, Cavagnini F, Franceschi C, Hofland LJ, Mari D,Janssen J.Author information:(1)Department of Clinical Sciences and Community Health, University of Milan,Milan, Italy.Centenarians' offspring represent a suitable model to study age-dependentvariables (e.g. IGF-I) potentially involved in the modulation of the lifespan.The aim of the present study was to investigate the role of the IGF-I in humanlongevity. We evaluated circulating IGF-I bioactivity measured by an innovativeIGF-I Kinase Receptor Activation (KIRA) Assay, total IGF-I, IGFBP-3, totalIGF-II, insulin, glucose, HOMA2-B% and HOMA2-S% in 192 centenarians' offspringand 80 offspring-controls of which both parents died relatively young. Bothgroups were well-matched for age, gender and BMI with the centenarians'offspring. IGF-I bioactivity (p〈0.01), total IGF-I (p〈0.01) and the IGF-I/IGFBP-3molar ratio (p〈0.001) were significantly lower in centenarians' offspringcompared to offspring matched-controls. Serum insulin, glucose, HOMA2-B% andHOMA2-S% values were similar between both groups. In centenarians' offspringIGF-I bioactivity was inversely associated to insulin sensitivity.IN CONCLUSION:1) centenarians' offspring had relatively lower circulating IGF-I bioactivitycompared to offspring matched-controls; 2) IGF-I bioactivity in centenarians'offspring was inversely related to insulin sensitivity. These data support a roleof the IGF-I/insulin system in the modulation of human aging process.PMCID: PMC3492223PMID: 22983440 Link to comment Share on other sites More sharing options...
Michael R Posted November 28, 2015 Report Share Posted November 28, 2015 Yeah, there are quite a few studies linking genetically low IGF-1 signaling to extreme longevity in humans. Link to comment Share on other sites More sharing options...
Brett Black Posted November 29, 2015 Report Share Posted November 29, 2015 My impression is still that evidence for IGF-1 impact on human longevity is inconsistent and unclear. I think the reviews from the experts agree with that position. I'm not sure speculations about IGF-1-related longevity in humans, currently largely extrapolated from mice, worms and yeast, through unspecified "anti-aging" mechanisms, should enter the equation when better human evidence supports protection or risk for specific pathologies of aging. When we look beyond mice, the lack of observed longevity benefits in IGF-1 deficient human Laron dwarfs and CR'ed rhesus monkeys adds further uncertainty about the translatability to humans.IGF-1 genetic association studies may not be applicable to diet-induced IGF-1 levels in adults if longevity benefits mainly derive from exposure during develpomental years of life. Another element of potential importance for some CR practitioners is that impaired glucose tolerance may be a significant CVD and stroke risk factor. This is not necessarily an either/or situation, as one doesn't require CR or lower protein diet to maintain a superb CVD risk profile. There may be alternative ways to lower risk of cancer too, like a plant-based diet, which has been shown to blunt the dietary protein/IGF-1/cancer association.One option is to look at the IGF-1 issue from a personal risk factor perspective: those with higher risk for cancer maybe should opt for lower IGF-1, those with higher risk for cardiovascular and cerebrovascular diseases and concern for maintaining bone, brain and muscle health maybe should opt for higher IGF-1. 1. Curr Vasc Pharmacol. 2014;12(5):674-81.Association between genetic variations in the insulin/insulin-like growth factor(Igf-1) signaling pathway and longevity: a systematic review and meta-analysis.Di Bona D, Accardi G, Virruso C, Candore G, Caruso C(1).Author information:(1)U.O. di Medicina Trasfusionale, AOUP Paolo Giaccone, Via del Vespro 129, 90127Palermo, Italy. danilodibona@yahoo.it.Some studies have shown that polymorphisms in the insulin growth factor-1 (IGF-1)signaling pathway genes could influence human longevity. However, the results ofdifferent studies are often inconsistent. Our aim was to investigate bysystematic review and meta-analysis the association of the common polymorphismsdefining the genetic variability of the IGF-1 signaling pathway associated withhuman longevity. Eleven studies investigating the association between thepolymorphisms in the IGF-1 signaling pathway genes (IGF-1, IGF-1 receptor(IGF-1R), Forkhead box O3A (FOXO3A) and Silent mating type Information Regulation1 (SIRT1) and longevity were found and analyzed. The modelfree approach wasapplied to meta-analyze these studies. No association was reported between thesingle nucleotide polymorphisms (SNPs) of IGF-1 and longevity in the onlyavailable study. The meta-analysis of available data from four studies, showed asignificant association with the IGF-1R polymorphism rs2229765, suggesting thatsubjects with the Abearing genotype have a greater chance of longevity.Concerning the five studies on FOXO3A SNPs, for the rs2764264 a significantassociation with longevity was observed for C allele when only males wereincluded in the analysis. Statistically significant results were obtained forother SNPs as well, i.e. rs2802292 (G allele), rs9400239 and rs479744 (T and Aalleles, respectively). For rs9400239 the association was observed in long livedmales with a lower odds ratio than in centenarians, while in rs479744 asignificant association was highlighted in centenarians. Concerning SIRT1, noassociation between the SNPs under study and longevity was observed in the onlyavailable report. Current findings suggest that both IGF-1R and FOXO3Apolymorphisms could be associated with longevity. The high degree ofbetween-study heterogeneity and the low number of available studies underline theneed for further methodologically adequate analyses to confirm this evidence.PMID: 24350933 [PubMed - indexed for MEDLINE]https://www.ncbi.nlm.nih.gov/pubmed/24350933 Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted December 29, 2015 Author Report Share Posted December 29, 2015 All, Yeah, there are quite a few studies linking genetically low IGF-1 signaling to extreme longevity in humans. Add to Michael's list, this new study [1] posted by Al Pater (thanks Al!). It followed nearly 1000 quite old (> 90) men and women from the Netherlands and looked at the association between their IGF-1 level and their survival and functional status. The researchers found that being in the lowest quartile of the IGF-1:IGFBP-3 ratio (i.e. those with the lowest level of bioavailable IGF-1) was associated with a 27% better change of survival relative to being in the highest quartile of bioavailable IGF-1. Furthermore, and perhaps as importantly, they found that being in the lowest quartile of bioavailable IGF-1 was associated with a significant 10-15% improvement in functional status, as measured by participants' ability to perform standardized activities of daily living (ADLs), and in a non-significant improvement in cognitive abilities, as measured by a Mini-Mental State Examination (MMSE). They also found "Interestingly, lower IGF-1/IGFBP3 molar ratios [i.e. lower bioavailable IGF-1] were associated with lower levels of non-fasted insulin" - which is in accordance with the results we low IGF-1 CR folks exhibit, i.e. also low serum insulin levels, and improved insulin sensitivity. An interesting quote from the free full text: It has been suggested that low levels of IGF-1 and/or reduced IGF-1 bioavailability form part of a survival response that can be constitutively active in long-lived individuals as well as elicited by diverse forms of stress, including metabolic stress, genotoxic stress and inflammation [and CR I would add! - Dean] (ref). ... In our study, levels of CRP and free triiodothyronine did not differ across quartiles of the IGF-1/IGFBP3 molar ratios, while functional status was better in the quartile with the lowest IGF-1/IGFBP3 ratio, in line with the observed survival benefit. So contrary to the suggestions mentioned above by Brett about possible downsides of low IGF-1, this study seems to suggest that we may be able to have our cake and eat it too. In other words, benefit from both increased longevity and improved performance (i.e. functional status), also as a result of, or at least associated with, low levels of bioavailable IGF-1. Of course, if by performance one means "ability to lift heavy weights", low IGF-1 is likely to be detrimental. But I don't think too many of us CR folks care much about performance in that sense. --Dean ----------- [1] Aging (Albany NY). 2015 Nov 12. [Epub ahead of print] Association analysis of insulin-like growth factor-1 axis parameters with survival and functional status in nonagenarians of the Leiden Longevity Study. van der Spoel E, Rozing MP, Houwing-Duistermaat JJ, Slagboom PE, Beekman M, de Craen AJ, Westendorp RG, van Heemst D. PMID: 26568155 Free Article http://www.impactaging.com/papers/v7/n11/full/100841.html http://www.impactaging.com/papers/v7/n11/pdf/100841.pdf Abstract Reduced insulin/insulin-like growth factor 1 (IGF-1) signaling has been associated with longevity in various model organisms. However, the role of insulin/IGF-1 signaling in human survival remains controversial. The aim of this study was to test whether circulating IGF-1 axis parameters associate with old age survival and functional status in nonagenarians from the Leiden Longevity Study. This study examined 858 Dutch nonagenarian (males=/>89 years; females=/>91 years) siblings from 409 families, without selection on health or demographic characteristics. Nonagenarians were divided over sex-specific strata according to their levels of IGF-1, IGF binding protein 3 and IGF-1/IGFBP3 molar ratio. We found that lower IGF-1/IGFBP3 ratios were associated with improved survival: nonagenarians in the quartile of the lowest ratio had a lower estimated hazard ratio (95% confidence interval) of 0.73 (0.59 - 0.91) compared to the quartile with the highest ratio (ptrend=0.002). Functional status was assessed by (Instrumental) Activities of Daily Living ((I)ADL) scales. Compared to those in the quartile with the highest IGF-1/IGFBP3 ratio, nonagenarians in the lowest quartile had higher scores for ADL (ptrend=0.001) and IADL (ptrend=0.003). These findings suggest that IGF-1 axis parameters are associated with increased old age survival and better functional status in nonagenarians from the Leiden Longevity Study. KEYWORDS: IGF-1 axis; familial longevity; functional status; human; survival Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted July 17, 2016 Author Report Share Posted July 17, 2016 We're famous again! In his weekly newsletter out today, Dr. Greger did a story on Calorie Restriction vs. Plant-Based Diets which highlighted results from two of Luigi's studies on us (PMIDs 18843793 and 17158430). He discusses the important health and lifespan benefits of keeping IGF-1 low, and uses Luigi's studies to (allegedly) argue that it is a plant-based diet, and not the reduced calories, that results in low IGF-1. I didn't remember this part of Luigi's study, which Dr. Greger used as evidence that it is the plant-based diet rather than CR that drops IGF-1: Therefore, we conducted additional studies to evaluate the importance of long-term protein intake in modulating serum IGF-1 concentration in humans. In one study, we evaluated serum IGF-1 and IGFBP-3 concentrations, and IGF-1 : IGFBP-3 ratio in 28 vegans who had been consuming a moderately protein-restricted (PR) diet (0.76 g kg−1 per day; ~10% of intake from protein) for ~5 years age-matched with 28 members of the Calorie Restriction Society who consume a high-protein diet (1.73 g kg−1 per day; ~24% of energy intake from protein) (Table 3). Protein intake was significantly lower in the moderately PR group than in the CR group, while energy intake tended to be higher (Table 3). Both serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio were significantly lower in the moderately PR diet group than in the severe CR diet group, whereas fasting insulin and C-reactive protein were similarly low in the moderately low-protein vegan and CR groups (Fig. 2), as previously reported in a smaller group of raw food vegans (Fontana et al., 2006a, 2007a). This effect of a moderate protein restriction is independent of body weight and body fat content, as serum total and free IGF-1 concentrations were lower in the moderately PR group than in the severe CR high-protein diet group, despite the PR groups’ higher body weight, BMI and body fat content (Table 4). Dr. Greger's summary of these results is pretty accurate: Only the vegan group got a significant drop in IGF-1. These findings demonstrate that, unlike in rodents, long-term severe caloric restriction in humans does not reduce the level of this cancer-promoting hormone. It’s not how many calories we eat, but the protein intake that may be the key determinant of circulating IGF-1 levels in humans, and so reduced protein intake may become an important component of anti-cancer and anti-aging dietary interventions. But once again Dr. Greger's agenda (bless his heart) shines through a bit. Given the title of this article ("Calorie Restriction vs. Plant-Based Diets") he seems to be hoping his readers will equate "plant-based" or "vegan" with "low protein". While generally this is the case, the two don't necessarily go together. It's possible to eat a high protein vegan diet (e.g. with concentrated soy products, vegan protein isolates etc), just as it's possible to keep protein low on a diet that includes animal products (not so easy, but ketogenic diet folks do it w/ lots of butter etc.). My personal data might seem to support Dr. Greger's conjecture. Since I eat a lot of calories, I also eat a lot of protein (96g/day, or 2x the RDI). But since I'm vegan, all of it plant-based and so my IGF-1 remains low (83, RR 61-200). In fact my IGF-1 now is less than half what it was when Luigi tested me in 11/2002, when (as I recall) I believe I was eating a lacto-ovo-(maybe pesco...)-vegetarian diet, with many fewer calories, more animal products, and about the same total protein. But don't hold me to that - since that was around that time I went vegan IIRC. Unfortunately I don't have records going back that far (except blood tests). Tom, anything in the archives? Regardless, my example is not very definitive anyways, because despite my high calorie and relatively high (plant-based) protein diet, I'm maintaining a net calorie deficit, which may explain my low IGF-1 level, independent of protein amount or source. So maybe it is low animal protein and not just low protein that makes the difference. But I don't think Dr. Greger makes a very good case for this hypothesis in his article, to put it mildly. --Dean Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted August 24, 2016 Author Report Share Posted August 24, 2016 I'm surprised we haven't had more discussion of this study by Fontana & Longo et al [1], featured in yesterday's Dr. Greger video. We've had brief mentions of it here, here and most recently on the IGT thread here, but it seems to me it deserves more attention. Recall it was the study that found lower protein intake (i.e. around the 50g/day RDA, rather than the excess most westerners eat) was associated with dramatically lower mortality in late middle age (50-65), but over 65, more protein is required to optimize health and longevity. In the first video below, Dr Greger highlights the results for the younger folks, focusing on the fact that it was animal (but not plant) protein that was associated with increased mortality in the 50-65 age group.The younger folks who were free from diabetes at baseline but ate the most (animal) protein, had a 73x (HR 73.52; CI 4.47 - 1209.7!) higher risk of dying from diabetes during follow-up than those non-diabetics who ate the least (i.e. close to RDA). Now that is one big hazard ratio! Dr. Greger, and [1] suggest the culprit is IGF-1, which is boosted by animal protein especially, and which promotes cancer growth. In the second video (from today), he focuses on the second part of [1], which found after age 65 more protein is associated with reduced cancer and all-cause mortality. He blames the increased risk associated with low protein in the elderly on age-related muscle loss, which occurs faster in old folks than youngsters. But then he points to studies showing that adding animal protein (eggs or milk) didn't help the elderly retain muscle. He says it take resistance training, weight bearing exercise, or (wait for it), eating more vegetables, to avoid late-life sarcopenia. To support that last point, he cites [2], a study from last year which followed over 3000 elderly Korean men and women to see how lifestyle factors and what they ate impacted muscle wasting. Verbally he describes the study's findings as: Consuming recommended levels of vegetables was associated with cutting the odds basically in half of low muscle mass. And he puts up a graphic of this quote from the paper: Consuming recommended levels of vegetables was associated with 48% lower odds of low muscle mass and engagement in recommended levels of aerobic exercise with 38% lower odds. But what he fails to mention was that this effect was only seen in women in [2]. Even in the abstract, [2] states quite plainly: In men, there were no associations between food group consumption and exercise and low muscle mass. Shame, shame Dr. Greger. One more instance where Dr. G spins the evidence to support a vegan lifestyle. I wholly endorse a vegan diet, but I'm often disappointed by his way of promoting it. The sentence he quotes does actually occur verbatim as he shows it in the graphic from his video, but as you can see in the passage below, he conveniently leaves out the "women" qualifier the occurs in the sentence prior to the one he quotes. Here is the relevant passage from the full text of [2] (my emphasis): In this study of a nationally representative sample of older Koreans, healthy lifestyle factors were inversely associated with low muscle mass in women, even after adjusting for covariates. Consuming recommended levels of vegetables was associated with 48% lower odds of low muscle mass and engagement in recommended levels aerobic exercise with 38% lower odds. Pretty underhanded Dr. G... Granted, there was a pretty strong trend in men towards improved muscle mass with high vegetable consumption, but it wasn't significant. Here are the covariate-adjusted hazard ratios for risk of low muscle mass in men and women who met the recommended vegetable intake thresholds (7 servings / day for men, 5 for women) vs. those who didn't: Men: HR 0.53, CI (0.18–1.60) Women: HR 0.52, CI (0.30–0.89) Later in the discussion the authors of [2] address the lack of apparent benefits of vegetables for muscle preservation in men as follows: In men, no significant association was found between the individual lifestyle factors and low muscle mass. More women than men achieved the recommended level of vegetable consumption, which may reflect the influence of diet on low muscle mass... However, it is uncertain why there was no significant relationship between lifestyle factors and low muscle mass in men. Inadequate adjustment for confounding may have influenced the results. Alternatively, lifestyle factors might play less of a role in low muscle mass in men than in women. The authors are right - only ¼ as many men as women (7% vs. 28%) met the vegetable intake recommendations, so the large confidence interval in men is probably explained in large part by the smaller sample of veggie-eating older Korean men. But still Dr. Greger, that's pretty cheesy what you did there, ignoring the null result in men. Based on the Longo and Fontana study, I agree with Dr. G's conclusion that it's likely we should eat more protein from plants in our elder years. But I'm pretty disappointed in Dr. Greger for the way he (once again) tries to spin the evidence to make it seem more of a slam-dunk in favor of plant protein than it actually is. Even for a good, and overall healthy cause like veganism, for me the ends don't justify the means, when the means means obfuscating or exaggerating the available evidence... --Dean --------- [1] Cell Metab. 2014 Mar 4;19(3):407-17. doi: 10.1016/j.cmet.2014.02.006. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Levine ME(1), Suarez JA(2), Brandhorst S(2), Balasubramanian P(2), Cheng CW(2), Madia F(3), Fontana L(4), Mirisola MG(5), Guevara-Aguirre J(6), Wan J(2), Passarino G(7), Kennedy BK(8), Wei M(2), Cohen P(2), Crimmins EM(1), Longo VD(9). Free full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988204/ Mice and humans with growth hormone receptor/IGF-1 deficiencies display major reductions in age-related diseases. Because protein restriction reduces GHR-IGF-1 activity, we examined links between protein intake and mortality. Respondents aged 50-65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer death risk during the following 18 years. These associations were either abolished or attenuated if the proteins were plant derived. Conversely, high protein intake was associated with reduced cancer and overall mortality in respondents over 65, but a 5-fold increase in diabetes mortality across all ages. Mouse studies confirmed the effect of high protein intake and GHR-IGF-1 signaling on the incidence and progression of breast and melanoma tumors, but also the detrimental effects of a low protein diet in the very old. These results suggest that low protein intake during middle age followed by moderate to high protein consumption in old adults may optimize healthspan and longevity. Copyright © 2014 Elsevier Inc. All rights reserved. DOI: 10.1016/j.cmet.2014.02.006 PMCID: PMC3988204 PMID: 24606898 - ------- [2] J Am Geriatr Soc. 2015 May;63(5):886-92. doi: 10.1111/jgs.13386. Epub 2015 Apr 27. Association between healthy diet and exercise and greater muscle mass in older adults. Kim J(1,)(2), Lee Y(1,)(2), Kye S(1), Chung YS(2,)(3), Kim KM(2,)(4). Author information: (1)Department of Preventive Medicine and Public Health, School of Medicine, Ajou University, Suwon, Korea. (2)Institute on Aging, Ajou University Medical Center, Suwon, Korea. (3)Department of Endocrinology and Metabolism, School of Medicine, Ajou University, Suwon, Korea. (4)Department of Family Practice and Community Health, School of Medicine, Ajou University, Suwon, Korea. Full text: http://sci-hub.cc/10.1111/jgs.13386 OBJECTIVES: To examine the association between healthy diet and exercise, individually and combined, and low muscle mass in older Korean adults. DESIGN: Population-based cross-sectional study from the Fourth and Fifth Korea National Health and Nutrition Examination Surveys from 2008 to 2011. SETTING: Community. PARTICIPANTS: Nationally representative sample aged 65 and older (1,486 men, 1,799 women) in the Republic of Korea. MEASUREMENTS: A food frequency questionnaire was used to determine frequency of food group consumption (meat, fish, eggs, legumes; vegetables; fruits). Participation in exercise (aerobic and resistance) was based on self-report. Combined healthy lifestyle factors were calculated as the number of recommendations met regarding consumption of food groups and exercise performed. Appendicular skeletal muscle mass (ASM) was measured using dual-energy X-ray absorptiometry, and low muscle mass was defined using the variable of ASM adjusted for weight. Logistic regression analysis was performed to examine the association between healthy lifestyle factors and low muscle mass, adjusting for sociodemographic characteristics and health-related variables. RESULTS: In women, after controlling for covariates, vegetable consumption (odds ratio (OR)=0.52, 95% confidence interval (CI)=0.30-0.89) and aerobic exercise (OR=0.62, 95% CI=0.39-1.00) were inversely associated with low muscle mass. Also, the odds of low muscle mass was lower in women with three or more healthy lifestyle factors versus none (OR=0.45, 95% CI=0.23-0.87). In men, there were no associations between food group consumption and exercise and low muscle mass. CONCLUSION: Older women who exercise and consume a healthy diet have lower odds of low muscle mass. Engaging in multiple healthy behaviors may be important in preventing low muscle mass in late life. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society. DOI: 10.1111/jgs.13386 PMID: 25912793 Link to comment Share on other sites More sharing options...
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