Beneficios Do Jejum - Brad Pilon

[Eduardo90 1494]

What fasting has done for me (self.fasting)

submitted

De novo esse papo de que jejum so serve pra praticidade ?

Eu concordo que jejum seja muito bom, mas, como já disseram ainda não existe uma ciência FORTE que indique uma superioridade com jejum EM PESSOAS SAUDÁVEIS. Não adianta mostrar 100 relatos de internet mostrando as vantagens do jejum em obesos, e doentes, isso não significa que é vantajoso para toda uma população.

Existem sim, pessoas que não se adaptam ao jejum, não se sentem bem, pra essas pessoas não é a melhor opção. Vou colocar aqui o que o próprio Dr Souto falou sobre o jejum, que é do mesmo texto do post original: "Antes que eu continue, uma advertência: esta abordagem é para adultos saudáveis. Não está indicada para pessoas pessoas em uso de determinadas medicações, especialmente para diabéticos em tratamento medicamentoso ou em uso de insulina (risco de vida)"

Pra quem é saudável e tem bons ganhos (que na verdade foi o que iniciou os posts de praticidade) não vai ter uma diferença gritante. Ou seja, se o cara tem dificuldades de comer 1~2 refeições por dia e só quer estética, não vai mudar nada.

Olhem o diário do Ricardo Queiroz, e você percebe que a única diferença no shape dele é retenção, que ele resolve tranquilamente com o jejum. Eu também sinto isso, meu shape melhora em jejum, mas não tem uma diferença gritante, eu sigo jejum porque gosto, se o cara não gosta não tem o porque mudar.

As pessoas que tem um grande avanço é porque provavelmente não conseguiam comer "certo" (kcals e macros) com deitas frequentes (2~2/3~3h)

De uma forma geral a consistência ainda é mais importante, tem um tópico MUITO bom do ales com a piramide da nutrição (aqui) onde o Eric Helms em ordem o que é mais importante (base) pro menos importante (pico), e que o foco deve ser na base, onde você deve manter 80% do esforço, e é o que vai dar mais resultado no final, principalmente se tratando de peso e composição corporal

1 - Balanço energético, calorias e taxa de variação de peso

2 - Macronutriente, composição da dieta e fibras

3 - Micronutriente, minerais, água

4 - Nutrient Timing e Frequência

5 - Suplementos

Frequência é o 4º degrau, ou seja, tem muita coisa pra se preocupar primeiro. Não adianta o cara ficar 20h em jejum e comer 5000 kcal, sem controle de macros e achar que vai ficar saudável e seco (sei que ninguém disse isso, é só pra ilustrar) ele vai precisar estar com tudo em ordem pro jejum ter vantagem, ou seja não é mágico, mas é muito prático

Abraços

Achei que tava claro no texto. Não acho que a janela seja menor que 24h nem nada do tipo. Entretanto, caso se queira otimizar a hipertrofia - o que provavelmente é mais válidos pra profissionais -, o ideal é fazer 3-4 refeições ricas em proteína, inclusive com o pré e o pós treinos com um intervalo de no máximo 5-6h - isso segundo o Alan Aragon e o Brad Schoenfeld, que são top especialistas no assunto dieta e hipertrofia, sem contar que o Lyle McDonald tem uma visão bem parecida.

Enfim, acho importante deixar claro que gosto mto de jejum, faço uso quando posso, me traz um bem estar mto grande, enfim... Não sou contra, acho que é ótimo pra queima de gordura, mas não tão bom (mas, ainda assim, perfeitamente viável) pra ganho de massa muscular.

Abraço

É o que eu penso

Pode funcionar, mas isso não quer dizer que seja melhor. Eu sigo jejum, porque gosto e me sinto bem, não sou atleta então sei que não vai ter uma diferença absurda no numero de refeições, prefiro me manter num plano que eu consiga seguir por MUITO tempo, ou seja prático e que eu goste também .

[EmilioTenório 366]

De uma forma geral a consistência ainda é mais importante, tem um tópico MUITO bom do ales com a piramide da nutrição (aqui) onde o Eric Helms em ordem o que é mais importante (base) pro menos importante (pico), e que o foco deve ser na base, onde você deve manter 80% do esforço, e é o que vai dar mais resultado no final, principalmente se tratando de peso e composição corporal

1 - Balanço energético, calorias e taxa de variação de peso

2 - Macronutriente, composição da dieta e fibras

3 - Micronutriente, minerais, água

4 - Nutrient Timing e Frequência

5 - Suplementos

Frequência é o 4º degrau, ou seja, tem muita coisa pra se preocupar primeiro. Não adianta o cara ficar 20h em jejum e comer 5000 kcal, sem controle de macros e achar que vai ficar saudável e seco (sei que ninguém disse isso, é só pra ilustrar) ele vai precisar estar com tudo em ordem pro jejum ter vantagem, ou seja não é mágico, mas é muito prático

Exato ;)

TUDO que a galera que faz acha superior.

AHH eu faço JI/WD e ela é superior a quem come de 3 em 3 horas;

AHH eu sigo uma dieta high carb/fat e ela é superior a uma low fat/carb;

AHH eu tomo suplemento X e ele é o melhor.

Isso não existe.

Como eu disse acima e repito: TUDO que a galera faz e adapta a seu dia a dia acha que é melhor e quer tornar isso uma verdade universal.

E reforçando o que você disse (se bem que já disse tudo):

Tendo uma boa base o resto é mero DETALHE.

Acredito em possíveis benefícios na parte da funcionalidade, mas esteticamente falando o ÚNICO fator que eu vejo é a melhora da retenção que pode ser facilmente adaptado a uma dieta de comer frequentemente.

Eu sigo dietas em jejum a muito tempo e simplesmente porque sou preguiçoso de ficar comendo o dia todo e gosto de mandar grandes refeições, mas muitas vezes eu tive que passar dias sem IF's e esteticamente falando não vi diferença nenhuma.

Não estou condenando as IF's, só quero dizer que como qualquer outra dieta/estilo de vida está muito longe de ser algo perfeito.

[planeta 5553]

jejuns, autofagia e regeneração do corpo, inclusive cerebro

151 Deter RL, De Duve C. Influence of glucagon, an inducer of cellular autophagy, on some

physical properties of rat liver lysosomes. J Cell Biol 1967;33:437–449

152 A.M. Cuervo, E. Bergamini, U.T. Brunk, W. Droge, M. Ffrench, A. Terman, Autophagy and

aging: the importance of maintaining ‘‘clean’’ cells, Autophagy 1 (2005) 131e140.

153 T Kanazawa, Ikue Taneike, Ryuichiro Akaishi, Fumiaki Yoshizawa, Norihiko Furuya,

Shinobu Fujimura, and Motoni Kadowaki. Amino Acids and Insulin Control Autophagic

Proteolysis through Different Signaling Pathways in Relation to mTOR in Isolated Rat

Hepatocytes. THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 279, No. 9, Issue of February

27, pp. 8452–8459, 2004

154 Glynn EL, Fry CS, Drummond MJ, Timmerman KL, Dhanani S, Volpi E, Rasmussen BB.

Excess leucine intake enhances muscle anabolic signaling but not net protein anabolism in

young men and women. J Nutr. 2010 Nov;140(11):1970-6.

155 Joon-Ho Sheen, Roberto Zoncu, Dohoon Kim, David M. Sabatini Defective Regulation of

Autophagy upon Leucine Deprivation Reveals a Targetable Liability of Human Melanoma Cells

In Vitro and In Vivo. Cancer Cell, Volume 19, Issue 5, 613-628, 17 May 2011

156 Ding, WX. The emerging role of autophagy in alcoholic liver disease Exp Biol Med 1 May

2011: 546-556.

157 Hara T, et al. Suppression of basal autophagy in neural cells causes neurodegenerative

disease in mice. Nature 2006; 441:885-9

158 Komatsu M, et al. Loss of autophagy in the central nervous system causes

neurodegeneration in mice. Nature 2006; 441:880-4

159 Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular

self-digestion. Nature 2008; 451:1069-75

160 Alirezaei M, Kiosses WB, Flynn CT, Brady NR, Fox HS. Disruption of neuronal autophagy by

infected microglia results in neurodegeneration. PLoS ONE 2008; 3:2906

161 Orvedahl A, Levine B. Eating the enemy within: autophagy in infectious diseases. Cell Death

Differ 2009; 16:57-69

162 Alirezaei M, Kemball CC, Flynn CT, Wood MR, Whitton JL, Kiosses WB. Short-term fasting

induces profound neuronal autophagy. Autophagy. 2010 Aug;6(6):702-10.

163 Hara, N., K. Nakamura, M. Matsui, A. Yamamato, Y. Nakahara, R. Suzuki-Migishima, M.

Yokoyama, K. Mishima, I. Saito, H. Okana, and N. Mizushima. Suppression of basal autophagy

in neural cells causes neurodegenerative disease in mice. Nature. In press

Eat Stop Eat 171

164Komatsu M, et al. Loss of autophagy in the central nervous system causes

neurodegeneration in mice. Nature 2006; 441:880-4

165 Jaeger PA, Wyss-Coray T. All-you-can-eat: autophagy in neurodegeneration and

neuroprotection. Mol Neurodegener 2009; 4:16

166 Hung SY, Huang WP, Liou HC, Fu WM. Autophagy protects neuron from Aβ-induced

cytotoxicity. Autophagy 2009; 5:502-10.

167 Donati A, Cavallini G., Paradiso C., Vittorini S., Pollera M., Gori Z. and E. B. Age-related

changes in the autophagic proteolysis of rat isolated liver cells: effects of antiaging dietary

restrictions. J Gerontol A Biol Sci Med Sci. 2001; 56: B375-383.

168 Rubinsztein DC. The roles of intracellular protein-degradation pathways in

neurodegeneration. Nature. 2006; 443: 780-786

169 K. Kirkegaard, M.P. Taylor, W.T. Jackson, Cellular autophagy: surrender, avoidance and

subversion by microorganisms, Nat. Rev. Microbiol. 2 (2004) 301e314

170 B. Levine, Eating oneself and uninvited guests: autophagy-related pathways in cellular

defense, Cell 120 (2005) 159e162

171 M. Ogawa, C. Sasakawa, Bacterial evasion of the autophagic defense system, Curr. Opin.

Microbiol. 9 (2006) 62e68

172 M.S. Swanson, Autophagy: eating for good health, J. Immunol. 177 (2006) 4945e4951.

173 Anson RM, et al. Intermittent fasting dissociates beneficial effects of dietary restriction on

glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci

USA 2003; 100:6216-20

174 Duan W, et al. Dietary restriction normalizes glucose metabolism and BDNF levels, slows

disease progression, and increases survival in huntingting mutant mice. Proc Natl Acad Sci

USA 2003; 100:2911-6

175 Tohyama D, Yamaguchi A and Yamashita T. Inhibition of a eukaryotic initiation factor

(eIF2Bdelta/F11A3.2) during adulthood extends lifespan in Caenorhabditis elegans. FASEB J.

2008; 22: 4327-4337

176 Nair U, Klionsky DJ. Activation of autophagy is required for muscle homeostasis during

physical exercise. Autophagy. 2011 Dec 1;7(12).

177 Sandri M. Autophagy in health and disease. 3.

http://www.medicalnewstoday.com/articles/277860.php

Results of a new study on mice and a phase 1 trial of humans suggest that prolonged cycles of fasting - for 2-4 days at a time - not only protect against toxic effects of chemotherapy, but also trigger stem cell regeneration of new immune cells and clearing out of old, damaged cells.

Short-term fasting induces profound neuronal autophagy

Mehrdad Alirezaei,#1 Christopher C. Kemball,#1 Claudia T. Flynn,1 Malcolm R. Wood,2 J. Lindsay Whitton,1 andWilliam B. Kiosses2

Author information ► Article notes ► Copyright and License information ►

This article has been cited by other articles in PMC.

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Abstract

Disruption of autophagy—a key homeostatic process in which cytosolic components are degraded and recycled through lysosomes—can cause neurodegeneration in tissue culture and in vivo. Upregulation of this pathway may be neuroprotective, and much effort is being invested in developing drugs that cross the blood brain barrier and increase neuronal autophagy. One well-recognized way of inducing autophagy is by food restriction, which upregulates autophagy in many organs including the liver; but current dogma holds that the brain escapes this effect, perhaps because it is a metabolically privileged site. Here, we have re-evaluated this tenet using a novel approach that allows us to detect, enumerate and characterize autophagosomes in vivo. We first validate the approach by showing that it allows the identification and characterization of autophagosomes in the livers of food-restricted mice. We use the method to identify constitutive autophagosomes in cortical neurons and Purkinje cells, and we show that short-term fasting leads to a dramatic upregulation in neuronal autophagy. The increased neuronal autophagy is revealed by changes in autophagosome abundance and characteristics, and by diminished neuronal mTOR activity in vivo, demonstrated by a reduction in levels of phosphorylated S6 ribosomal protein in Purkinje cells. The increased abundance of autophagosomes in Purkinje cells was confirmed using transmission electron microscopy. Our data lead us to speculate that sporadic fasting might represent a simple, safe and inexpensive means to promote this potentially therapeutic neuronal response.

Key words: autophagy, fasting, Purkinje cells, cortical neurons, confocal microscopy, electron microscopy, neuroprotection, starvation, CNS, cortex

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Introduction

Autophagy is a key homeostatic mechanism whose physiological importance is reflected by its preservation throughout the eukaryotic phylogenetic tree, from yeast to mammals. In recent years, autophagy has been recognized as a crucial defense mechanism against malignancy, infection and neurodegenerative diseases.1–5Abrogation of autophagy in neurons can lead to neurodegenerative disease1,2,4 and autophagy may play a role in the development of Alzheimer disease; indeed, enhancement of autophagy has been proposed as one possible treatment for this coming plague.6–8 Consequently, substantial research effort is being expended on attempts to develop drugs that can upregulate neuronal autophagy in the intact CNS. Herein we provide evidence to support the notion that the desired physiological goal may be attained by a simple, safe and inexpensive alternative approach: short-term food restriction.

Studies in yeast, and in tissue culture, have contributed significantly to our understanding of the molecular events that are involved in autophagy and its regulation. However, it has been difficult to observe the process in intact organs and tissues, and most especially in the brain.9 This is not due to the lack of in vivo mammalian models. For example, to facilitate the identification and analysis of autophagy in vivo, a transgenic mouse has been generated10,11 that encodes a fusion between GFP and microtubule-associated protein 1 light chain 3 (LC3). The lipidated form of LC3 specifically associates with autophagosomes12 and this protein is, currently, the most widely used marker of autophagy in mammalian cells. Others have used these GFP-LC3 mice to determine the effects of food restriction in vivo. It is well known that food restriction induces autophagy in many organs and tissues,9,10 but autophagy has not previously been detected in the brain even after 48 hours of food restriction; because of this, it has been proposed that the brain is metabolically privileged13,14 and that a more severe insult—e.g., a direct injury mediated by local ischemia or trauma—may be required to trigger an autophagic response within this organ.15,16 Herein, we combine two wellcharacterized techniques to investigate the effect of a brief period of food restriction on neuronal autophagy. We show that this approach identifies autophagosomes at a resolution that allows them to be not only enumerated, but also characterized in some detail. In addition, we have used a standard approach—transmission electron microscopy (TEM)—to confirm the increased abundance of autophagosomes in neurons of food-restricted mice. Our data demonstrate that, contrary to current dogma, food restriction causes a rapid and profound upregulation of autophagy in the brain.

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Results

Six- to seven-week old male GFP-LC3 mice were food-restricted for 24 or 48 hours, a process known to induce fatty change and autophagy in the liver.9,10 Water was available ad libitum. These mice, and non-food-restricted control mice, were euthanized (with PBS perfusion) and vibratome sections of liver and brain were prepared and stained as described in Experimental Procedures. Confocal images were captured and analyzed.

Confocal microscopy of vibratome sections identifies autophagosomes in the livers of food-restricted mice.

We first validated the method by analyzing the liver, an organ in which autophagy is known to be induced by food restriction. Representative confocal images of liver are shown in Figure 1A. As expected, essentially no GFP signal was present in the liver of a C57BL/6 mouse. In normal-fed GFP-LC3 mice, GFP signal was detectable in hepatocytes, and was distributed throughout the cytosol. Following 24 hours of food restriction, individual autophagosomes could be detected as discrete regions of high fluorescence, and autophagosomes were even more abundant after 48 hours. The high resolution of the approach allowed quantitative analyses of individual autophagosomes. We were able to measure not only the number of vesicles per cell, but also their area, perimeter, feret (the longest diameter within an enclosed irregular shape), and circularity (Fig. 1B). The first response to food restriction, observed at 24 hours, was a significant increase in number. Autophagosome characteristics also changed, with increases in perimeter and in feret, a decreased circularity and a slight increase in area. All of these changes were magnified after 48 hours of food restriction. Importantly, the physical characteristics of these autophagosomes are similar to those previously reported using conventional electron microscopy methods, which have established the average diameters of autophagosomes as 0.5–1.5 µm; this validates the use of our new approach for quantitative analyses. These findings can be visualized at high resolution in three dimensions in Supplementary videos 1 through 4. The approach next was applied to two regions of the brain in normalfed and food-restricted GFP-LC3 mice.

Figure 1

Identification and quantitation of autophagosomes in the liver of food-restricted mice. GFP-LC3 transgenic mice were food-restricted (food-rest) to activate autophagy, and 24 or 48 hours later, the liver was harvested and the induction of autophagy was ...

Autophagosomes are detectable in cortical neurons of normal-fed mice, and their abundance and characteristics are markedly altered by short-term food restriction.

Figure 2, and Supplementary videos 5 and 6, show analyses of the cerebral cortex of normal-fed and food-restricted GFP-LC3 mice. Figure 2A shows representative flattened images; ( presents quantitative evaluations of autophagosomes in neuronal cell bodies using the five criteria described above; and © shows an isosurface rendering of the nuclei, autophagosomes and dendritic processes of several cortical neurons. Autophagosomes were readily detectable in cortical neurons of normal-fed mice (Fig. 2A, top row). To our knowledge, this is the first in vivo demonstration of autophagosomes in the cortical neurons of normal-fed mammals. These vesicles were few in number and small in size (Fig. 2B). Food restriction caused a marked increase in both the number and the size of neuronal autophagosomes in the cell body of cortical neurons; these changes were present after 24 hours of food restriction (Fig. 2A, middle row), and were even more dramatic at 48 hours (Fig. 2A and bottom row). As was observed in the liver (Fig. 1), when compared to autophagosomes in normal-fed mice, those present in the cortical neurons of mice that had been food-restricted for 48 hours showed reduced circularity, with concomitantly increased feret and perimeter (Fig. 2B). Changes in GFP-LC3 signal also were observed in the neuronal cell processes (Fig. 2A, middle row); compared to normal-fed mice, the signal was increased by >3-fold in neurites at 24 hours (p = 0.004, data not shown), but diminished to resting levels after 48 hours. Others have proposed that neuronal autophagosomes are present in neurites and that they undergo retrograde translocation to the cell body, where they fuse with neuronal lysosomes that reside in a juxtanuclear location.17,18 We speculate that food restriction enhances this retrograde traffic, and that the appearance after 24 hours represents an in vivo snapshot of this event; and that it may be completed by 48 hours. To confirm that the cortical neurons of food-restricted mice did, indeed, contain autophagosomes, we evaluated the cells by TEM. A representative image is shown in Figure 2D. These data show clearly that, contrary to current dogma, food restriction increases autophagosome formation and/or accumulation within the brain; and, specifically, within cortical neurons. We considered it important to determine if these changes were limited to cortical neurons or, conversely, were more widespread within the brain. To this end, we evaluated the effects of food restriction on Purkinje cells of the cerebellum.

Figure 2

Identification and quantitation of autophagosomes in the cerebral cortex of food-restricted mice. GFP-LC3 transgenic mice were food-restricted for 24 or 48 hours, and then the brain was isolated and sagittal vibratome-cut sections were analyzed by confocal ...

Purkinje cells in the cerebella of food-restricted mice contain greater numbers of autophagosomes and show reduced mTOR function.

Analyses of the cerebellum (Fig. 3A and Suppl. videos 7 and 8) identified small autophagosomes in the Purkinje cells of normal-fed mice, perhaps indicative of the basal level of autophagy that is thought to occur in this cell type.1,2,19 Furthermore, we observed marked alterations in the accumulation of GFP-LC3 signal in Purkinje cells in response to food restriction; there was a substantial increase in signal in the cell bodies of Purkinje neurons at both 24 and 48 hours. Some of the increased GFP-LC3 signal in Purkinje cells was more diffuse than had been observed in cortical neurons, forming a reticular perinuclear pattern that occupied a substantial proportion of the cell body. These findings are consistent with fusion of autophagosomes with lysosomes. The perinuclear distribution of autophagosomes induced by food restriction differs markedly from the changes that have been reported in degenerating Purkinje neurons of lurcher mice.19 In addition to this perinuclear pattern, discrete green puncta could be identified within the cell somata (Fig. 3A and Suppl. video 8). Next, we evaluated the in vivo activity of the protein mTOR (mammalian target of rapamycin), which plays a central role in the regulation of autophagy. mTOR exerts an inhibitory effect on autophagy, and mTOR activity is inversely correlated with autophagy. mTOR is highly active in cells in a nutrient-rich environment (in which autophagy is at a basal level), but nutrient deprivation decreases mTOR activity, leading to increased autophagy. Therefore, we investigated the possibility that food restriction might reduce mTOR activity in Purkinje cells in vivo. The measurement of mTOR activity in living cells is indirect, relying on the evaluation of downstream targets. mTOR activates the p70 S6 kinase which, in turn, phosphorylates its ribosomal substrate, S6RP; consequently, the abundance of phospho-S6RP in a living cell is directly related to mTOR activity, and is inversely related to the level of cellular autophagy. Figure 3Bcompares the cerebellum of a normal-fed mouse to that of a 48-hour food-restricted animal. The increase in GFP-LC3 signal following food restriction is again evident (left column) and there is a dramatic reduction in the level of phospho-S6RP in the Purkinje cell bodies of food-restricted mice (middle column). The merged image (right column) highlights the starvation-induced increase in autophagy that occurs in these neurons.

Figure 3

Identification of autophagosomes and reduction of mTOR activity in the cerebellum of food-restricted mice. (A) Low magnification flattened images of GFP-LC3 fluorescence were re-assembled to generate a complete sagittal cross-section of cerebellum from ...

The increase in number and in size of autophagosomes in cerebellar Purkinje cells of food-restricted mice are confirmed by TEM.

Finally, we used TEM to assess starvation-induced changes in autophagosomes in cerebellar Purkinje cells. In normal-fed mice, the autophagosomes were small (∼0.2 µm diameter, Fig. 4A left part), perhaps explaining the somewhat reticular appearance that was observed by confocal microscopy (Fig. 3). In contrast, the double-membraned structures in 48 hour foodrestricted mice were larger (∼0.5 µm in diameter; Fig. 4A middle & right parts); this size is similar to that of the green puncta that are visible in Figure 3 and inSupplementary video 8. Thus, food restriction appears to change the size of autophagosomes in Purkinje cells; does it also alter their abundance? TEM sections of the somata of Purkinje cells were examined and autophagosomes were enumerated. A representative section (Fig. 4B) shows the soma of a single Purkinje neuron from a mouse that had been food-restricted for 48 hours. Four autophagosomes (all ∼0.5 µm in diameter) are visible in this section; they are enclosed in colored boxes, and higher-magnification views are provided; white arrows indicate the autophagosomes. For both normal-fed and food-restricted mice, ∼20 different Purkinje cells were examined in this way, and autophagosomes were enumerated. As shown in Figure 4B (graph at lower right), there was a 3- to 4-fold increase in the number of autophagosomes in Purkinje cells from food-restricted animals (p < 0.0002). This increase in abundance is similar in extent to that observed in cortical neurons using our novel approach of vibratome sectioning and confocal microscopy (Fig. 2B).

Figure 4

TEM identification and quantitation of autophagosomes in Purkinje cells of normal-fed and food-restricted mice. (A) Images from Purkinje cells of normal-fed (left) or 48 hour food-restricted (middle & right) mice are shown. ( A single Purkinje ...

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Discussion

Sporadic short-term fasting, driven by religious and spiritual beliefs, is common to many cultures and has been practiced for millennia, but scientific analyses of the consequences of caloric restriction are more recent. Published studies indicate that the brain is spared many of the effects of short-term food restriction, perhaps because it is a metabolically privileged site that, relative to other organs, is protected from the acute effects of nutrient deprivation, including autophagy.17 We show here that this is not the case: short-term food restriction induces a dramatic upregulation of autophagy in cortical and Purkinje neurons. To our knowledge, this is the first demonstration that food restriction leads to in vivo neuronal autophagy. Our data extend recent reports in tissue culture systems,18,20 and have implications for individuals who, by choice or necessity, have limited food intake. Our findings also may have therapeutic implications, as outlined below. Autophagy is sometimes referred to as cellular “cleansing”, and our observations provide an attractive neuronal parallel to the organismal benefits that, historically, are perceived to derive from fasting.

In this study we describe a novel technique to identify and characterize autophagosomes in the tissues of GFP-LC3 mice, using vibratome sections and confocal microscopy. The changes that we report using this method are confirmed using the standard technique of TEM; this both validates the new approach, and confirms the conclusions that we have drawn therefrom. Herein, we make at least three novel observations.First, we identify and localize autophagosomes in cortical and Purkinje neurons of normal-fed mammals.Second, we show that, in these CNS neurons, short-term food restriction leads to a marked increase in the number of autophagosomes, together with changes in their physical characteristics. In principle, the observed changes could result either from increased production of autophagosomes, or from reduced fusion of autophagosomes with lysosomes. We believe that the former explanation is the more likely, because the activity of mTOR, a key protein that restrains autophagy, is reduced in the Purkinje cells of food-restricted mice (Fig. 3B). Thus, our data favor the interpretation that the increased abundance of autophagosomes results from upregulation of the autophagy pathway in neurons, rather than from the blockade of autophagosome maturation, although some contribution from the latter cannot be excluded.

Third, we demonstrate that the changes that are induced by food restriction differ somewhat depending on the neuronal cell type. This is consistent with the recent proposal that autophagy pathways may differ among cell types, as a result of evolutionary adaptation to the specific physiological needs of the cell.14 Published studies in which autophagy was inhibited have shown that the outcome varies with cell or tissue type. For example, interruption of neuronal autophagy can lead to degenerative disease,1,2 but an equivalent block in pancreatic acinar cells causes no overt dysfunction.21 However, until now it has been thought that increased autophagy would result in phenotypically-similar changes in closely-related cell types. Here we show that this appears not to be the case in vivo. Following food restriction, we observed both similarities and differences in the size and distribution of autophagosomes in cortical neurons and Purkinje cells. The fact that the observed changes in autophagy differed between these two neuronal cell types suggests that a more extensive analysis is warranted, to determine the extent to which short-term food restriction induces autophagy—and, possibly, other changes—in the mammalian CNS.

Our observation that a brief period of food restriction can induce widespread upregulation of autophagy in CNS neurons may have clinical relevance. As noted above, disruption of autophagy can cause neurodegenerative disease, and the converse also may hold true: upregulation of autophagy may have a neuroprotective effect. For example, in vitro models have shown that starvation in neuronal cell lines can remove toxic molecules and damaged mitochondria from neurons.22–24 Other tissue culture studies, of mutant huntingtin and α-synuclein proteins (which are associated with Huntington disease and familial Parkinson disease respectively), have identified autophagy substrates that can be removed by drug-induced enhancement of autophagy. Most importantly, some neuroprotective effects of drug-enhanced autophagy also have been observed in vivo, in a D. melanogaster model of Huntington disease.25 Finally, it has been suggested that intermittent fasting might improve neuronal function by means that are entirely independent of caloric intake, and may instead reflect an intrinsic neuronal response that is triggered by fasting;26,27 we speculate that the reported improvement of neuronal function may be related to the upregulation of autophagy that we show here. The above findings have encouraged the development of drugs that might enhance neuronal autophagy, thereby protecting against disease. Such drugs must: (i) be able to cross the intact blood-brain barrier; (ii) upregulate neuronal autophagy; and (iii) be harmless to the recipient. Food restriction is a simple, reliable, inexpensive and harmless alternative to drug ingestion and, therefore, we propose that short-term food restriction may represent an attractive alternative to the prophylaxis and treatment of diseases in which candidate drugs are currently being sought. However, caution is counseled, because studies in rat brain have suggested that chronic starvation might inhibit autophagy,28 an outcome that could damage, rather than protect, neurons.28,29

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Materials and Methods

Mice.

GFP-LC3 mice contain a transgene encoding an eGFP-rat LC3 fusion protein.10 GFP-LC3 transgenic mice, back-crossed to the C57BL/6 background, were obtained from Riken BioResource Center, and maintained as homozygous transgenic (Tg/Tg). Homozygous transgenic mice were bred with wild-type C57BL/6 mice to generate heterozygous transgenic (Tg/+) mice. Pathogen-free C57BL/6J mice were purchased from the Scripps Research Institute (TSRI) breeding facility or from Jackson Laboratories. Mice were housed in a temperature-controlled environment with 12-hr light/dark cycles where they received food and water. For studies on the effects of food restriction, 6–7 week old male C57BL/6J and GFP-LC3 (Tg/+) mice were deprived of food for 24 or 48 hr. These mice had free access to drinking water. All experimental procedures with mice were conducted in accordance with the guidelines of the National Institutes of Health Guide for the Care and Use of Laboratory Animals. All animal protocols were approved by TSRI Animal Care and Use Committee.

Perfusion, fixation and sectioning of tissues.

Mice were perfused with Dulbecco's PBS (DPBS, Invitrogen, 14040-141), and tissues were harvested and fixed using buffered zinc formalin (Z-FIX; Annatech Ltd., 171) at room temperature (RT) overnight. The inclusion of zinc is important, because it limits the extensive cross-linking that would occur with formalin alone, thereby preserving protein antigenicity and enhancing reagent penetration into the tissue section; but the residual cross-linking is sufficient to prevent the leaching of small molecules from cells.30 After overnight fixation, the fixative was replaced with PBS containing 0.1% (w/v) sodium azide on the following day, and the organs were preserved at 4°C. Sixty µm sections of brain were cut with a Leica VT 1000S vibratome.

Immunostaining of liver and brain vibratome sections.

Free-floating vibratome-cut liver sections (60 µm) were washed 3X in PBS (5 min each) and permeabilized in PBS with 0.5% Triton X-100 for 2 hrs at RT. Next, the liver sections were washed 3X in PBS and then incubated with Alexa Fluor 568 phalloidin (1:40; Invitrogen, A12380) in PBS with 1% normal goat serum (NGS; Invitrogen, PCN5000) and 0.3% Triton X-100 at 4°C overnight to label F-actin. After incubation, the sections were washed 5X in PBS and then counterstained with Hoechst 33342 (1:1,000; Invitrogen, H3570) for 1 hr at RT to label nuclei, and mounted with Vectashield (Vector labs, H1000) for confocal microscopy. Sagittal free-floating brain sections were washed 3X in PBS, permeabilized (similarly to the liver), and then blocked in PBS with 5% NGS and 0.3% Triton X-100 for 2 hrs at RT. Sections were washed 3X in PBS with 0.3% Triton, and incubated for ∼42–44 hrs at 4°C with the following primary antibodies diluted in 1% NGS and 0.3% Triton: mouse Milli-Mark Pan Neuronal Marker (1:50, Millipore, MAB2300); rabbit antibody against phospho- S6 ribosomal protein (phospho-S6RP; 1:100, Cell Signaling Technology, 2211); and rabbit anti-glial fibrillary acidic protein (GFAP; 1:500, DAKO, Z0334). The sections were then washed 3X in PBS with 0.3% Triton, and incubated for 2 hrs at RT with the following secondary antibodies (1:250, all from Invitrogen): goat anti-mouse IgG rhodamine red (R6393), donkey anti-rabbit IgG AlexaFluor 647 (A31573), and/or goat anti-rabbit IgG rhodamine red (R6394) diluted in 1% NGS and 0.3% Triton. After incubation, the sections were washed 5X in PBS. All brain sections were counterstained with Hoechst 33342 (1:1,000) for 1 hr at RT and mounted with Vectashield for confocal microscopy. As much as possible, all sections were protected from light throughout these procedures.

Confocal laser scanning microscopy analysis: high resolution imaging of autophagy in tissues.

Confocal images were captured using a Zeiss LSM 710 Laser Confocal Scanning Microscope running Zen 2009 Zeiss software suite. Representative regions within each vibratome section of brain were scanned as 8-bit optical sections (either 512 × 512 or 1,024 × 1,024 image sizes) and reconstructed for analysis. Exposure and image acquisition settings were identical for all sections. The observed green (GFP-LC3) signals did not result from autofluorescence because: (i) narrow band filters were used and the signals were observed only in the green channel and (ii) the signals were absent from non-transgenic mice (See Fig. 1).

Image processing, 3D reconstruction and quantitative analysis of GFP-LC3 vesicles.

All serial optical image sections (obtained at 0.3–0.5 µm interval step slices) were imported and spatially re-assembled using Imaris (BitPlane Inc.) or Zen 2009 (Carl Zeiss Inc.) software to generate a 3-dimensional representation of the tissue and rotational movies. All images were then maximum projected for 2D analysis in Image Pro Plus (Media Cybernetics Inc.) or Image J (NIH, http://rsbweb.nih.gov/ij/) software for quantitative image analysis. For all quantitation, serial confocal stacks were first maximum projected/flattened into one 8-bit 2D image per scanned region, and then further processed in Image Pro-Plus/3DS and Image J. Processing consisted of automatically outlining each cell with a tracing tool and then defining the background level of GFP-LC3 fluorescent signal using the threshold tool. Once traced, the fluorescent areas within each cell were individually outlined by the software and used to calculate 2D parameters including: the number of vesicles, area (assuming a uniform height), perimeter, feret (the longest diameter within an irregular shape), and circularity (a deviation from roundness of a sphere). To ensure valid comparisons of signal intensities among various images, all images and all colors were processed using identical software settings.

Transmission electron microscopy.

Mice were perfused with 0.9% saline followed by 4% paraformaldehyde, 1.5% glutaraldehyde in 0.1 M cacodylate buffer with 1 mM CaCl2. The brain was removed and immersed in the above fixative on ice for 6 hrs, and then was transferred to 2.5% glutaraldehyde in 0.1 M cacodylate buffer + 1 mM CaCl2 for overnight fixation. After a buffer wash, the tissue was further fixed in 1% OsO4 with 1.5% potassium ferricyanide in 0.1 M Na cacodylate and again washed in cacodylate buffer, dehydrated in graded ethanols and transitioned in propylene oxide. Tissue sections were embedded in Embed 812/Araldite (Electron Microscopy Sciences). Thick sections (1–2 µm) were cut, mounted on glass slides and stained in toluidine blue for general assessment in the light microscope. Subsequently, 70 nm thin sections were cut, mounted on copper slot grids coated with parlodion and stained with uranyl acetate and lead citrate for examination on a Philips CM100 electron microscope (FEI, Hillsbrough OR) at 80 kV. Images were collected using either an SIA-12C camera (Scientific Instruments and Applications) or a Megaview III CCD camera (Olympus Soft Imaging Solutions).

Statistics.

Statistical significance was determined by: (i) a one-way analysis of variance (ANOVA), and Tukey's post-hoc test was used for multiple comparisons within each data set (GraphPad Prism, GraphPad Software, Inc.) or (ii) Student's t test (Microsoft Excel 2007). In all cases, a p value <0.05 was considered statistically significant.

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Acknowledgements

We are grateful to Annette Lord for excellent secretarial support, and to Janet Weber and Hanna Lewicki for technical assistance and advice. This work was supported by NIH R01 awards AI-027028, AI-042314 and AI-077607 (J.L.W.); and by NIH T32 award NS41219 (C.C.K.). This is manuscript number 19985 from the Scripps Research Institute.

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Footnotes

Previously published online: www.landesbioscience.com/journals/autophagy/article/12376

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References

1. Hara T, et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice.Nature. 2006;441:885–889. [PubMed]

2. Komatsu M, et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice.Nature. 2006;441:880–884. [PubMed]

3. Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature. 2008;451:1069–1075. [PMC free article] [PubMed]

4. Alirezaei M, Kiosses WB, Flynn CT, Brady NR, Fox HS. Disruption of neuronal autophagy by infected microglia results in neurodegeneration. PLoS ONE. 2008;3:2906. [PMC free article] [PubMed]

5. Orvedahl A, Levine B. Eating the enemy within: autophagy in infectious diseases. Cell Death Differ.2009;16:57–69. [PMC free article] [PubMed]

6. Mizushima N. Aβ generation in autophagic vacuoles. J Cell Biol. 2005;171:15–17. [PMC free article][PubMed]

7. Nixon RA. Autophagy, amyloidogenesis and Alzheimer disease. J Cell Sci. 2007;120:4081–4091.[PubMed]

8. Yu WH, et al. Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease. J Cell Biol. 2005;171:87–98. [PMC free article] [PubMed]

9. Martinet W, De Meyer GR, Andries L, Herman AG, Kockx MM. In situ detection of starvation-induced autophagy. J Histochem Cytochem. 2006;54:85–96. [PubMed]

10. Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell. 2004;15:1101–1111. [PMC free article] [PubMed]

11. Mizushima N, Kuma A. Autophagosomes in GFP-LC3 Transgenic Mice. Methods Mol Biol.2008;445:119–124. [PubMed]

12. Kabeya Y, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000;19:5720–5728. [PMC free article] [PubMed]

13. Boland B, Nixon RA. Neuronal macroautophagy: from development to degeneration. Mol Aspects Med.2006;27:503–519. [PubMed]

14. Yue Z, Wang QJ, Komatsu M. Neuronal autophagy: going the distance to the axon. Autophagy.2008;4:94–96. [PMC free article] [PubMed]

15. Koike M, et al. Inhibition of autophagy prevents hippocampal pyramidal neuron death after hypoxic-ischemic injury. Am J Pathol. 2008;172:454–469. [PMC free article] [PubMed]

16. Lai Y, et al. Autophagy is increased after traumatic brain injury in mice and is partially inhibited by the antioxidant γ-glutamylcysteinyl ethyl ester. J Cereb Blood Flow Metab. 2008;28:540–550. [PubMed]

17. Komatsu M, et al. Constitutive autophagy: vital role in clearance of unfavorable proteins in neurons. Cell Death Differ. 2007;14:887–894. [PubMed]

18. Du L, et al. Starving neurons show sex difference in autophagy. J Biol Chem. 2009;284:2383–2396.[PMC free article] [PubMed]

19. Wang QJ, et al. Induction of autophagy in axonal dystrophy and degeneration. J Neurosci.2006;26:8057–8068. [PubMed]

20. Young JE, Martinez RA, La Spada AR. Nutrient deprivation induces neuronal autophagy and implicates reduced insulin signaling in neuroprotective autophagy activation. J Biol Chem. 2009;284:2363–2373.[PMC free article] [PubMed]

21. Hashimoto D, et al. Involvement of autophagy in trypsinogen activation within the pancreatic acinar cells. J Cell Biol. 2008;181:1065–1072. [PMC free article] [PubMed]

22. Jaeger PA, Wyss-Coray T. All-you-can-eat: autophagy in neurodegeneration and neuroprotection. Mol Neurodegener. 2009;4:16. [PMC free article] [PubMed]

23. Marazziti D, et al. Induction of macroautophagy by overexpression of the Parkinson's disease-associated GPR37 receptor. FASEB J. 2009;23:1978–1987. [PubMed]

24. Hung SY, Huang WP, Liou HC, Fu WM. Autophagy protects neuron from Aβ-induced cytotoxicity.Autophagy. 2009;5:502–510. [PubMed]

25. Sarkar S, et al. Small molecules enhance autophagy and reduce toxicity in Huntington's disease models.Nat Chem Biol. 2007;3:331–338. [PMC free article] [PubMed]

26. Anson RM, et al. Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci USA. 2003;100:6216–6220. [PMC free article] [PubMed]

27. Duan W, et al. Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice. Proc Natl Acad Sci USA. 2003;100:2911–2916. [PMC free article] [PubMed]

28. Hanahisa Y, Yamaguchi M. Characterization of calcium accumulation in the brain of rats administered orally calcium: the significance of energy-dependent mechanism. Mol Cell Biochem. 1996;158:1–7.[PubMed]

29. Sarkar S, Ravikumar B, Floto RA, Rubinsztein DC. Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies. Cell Death Differ. 2009;16:46–56. [PubMed]

30. Ott SR. Confocal microscopy in large insect brains: zinc-formaldehyde fixation improves synapsin immunostaining and preservation of morphology in whole-mounts. J Neurosci Methods. 2008;172:220–230.[PubMed]

Articles from Autophagy are provided here courtesy of Landes Bio

[Lucas, o Schrödinger 11998]

Pra vcs verem q eu não tenho nada contra o jejum , segue estudo com a conclusão de que o jejum não aumenta a ingestão calórica ad libitium na refeição pós jejum:

http://www.ncbi.nlm.nih.gov/m/pubmed/26278005/

"Conclusions: We demonstrate for the first time that, in obese adults, extended morning fasting does not cause compensatory intake during an ad libitum lunch nor does it increase appetite during the afternoon. Morning fasting reduced satiety hormone responses to a subsequent lunch meal but, counterintuitively also reduced concentrations of the appetite-stimulating hormone acylated ghrelin during the afternoon relative to lunch consumed after breakfast."

Editado Agosto 25, 2015 às 23:10 por Shrödinger

[Lucas, o Schrödinger 11998]

Segue post do Brad Schoenfeld no FB que coaduna com o que tenho dito aqui:

"More evidence that eating frequency does not substantially impact weight management. From the conclusion: "While it is unlikely that any 1 recommendation on eating frequency will be universally applicable, the most useful dietary advice regarding weight management for adults may be to focus on energy intake rather than eating frequency." With that said, it's important to point out that this is not necessarily applicable to those who are looking maximize muscle development and/or get down to very low body fat levels."

http://lm.facebook.com/l.php?u=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F25398748&h=VAQF4BGlx&enc=AZMurMRf7DbIuMhCtWCtTYHJPSRtGQLU-UCueCXeXR6L2bgptfw6kt3Z8dZG6Kvjd0w&s=1

Editado Agosto 25, 2015 às 11:27 por Shrödinger

[Eduardo90 1494]

Fala Planeta

Não precisava quotar, eu tinha visto a primeira vez, e achei MUITO bom mesmo. E eu não duvido que pra saúde jejum e low carb (moderação) são provavelmente a melhor opção. Tanto que eu sigo as duas WD+LC

Mas é que a questão que o Fuark levantou é pra shape (composição corporal). De verdade quem já testou sabe que não vai ter diferença absurda no shape, se você comer a mesma quantidade de calorias e macros (e mesmos alimentos) em 1 refeição ou em 8. Você não vai ficar mais gordo, nem mais forte, nada, não tem diferença significativa.

Aquele gráfico de GH é bem interessante, mas fora pra saúde, ele vai realmente ser capaz de modificar o shape significativamente, pelo que eu vi em mim, e em quem segue, não, e como eu disse, eu acho (tenho certeza) que meu shape fica com um aspecto melhor durante os jejuns, mas a diferença não é gritante, pra quem tem dificuldade de seguir jejum por causa da rotina, não vale a pena ficar se sacrificando se a pessoa está apenas visando ESTÉTICA

Como o Lucas falou, pra saúde é bem promissor, e EU não tenho dúvidas que seja a melhor opção. Por exemplo você sitou um estudo com melhoras durante a quimio, e veja é justamente em uma pessoa não saudável. Você teria algum estudo com um número legal de participantes, com dietas controladas, sendo que a única diferença seja a frequência ?

Estamos na mesma direção Planetinha, eu concordo com você, e sigo jejum, mas não vou mentir dizendo que todo mundo vai melhorar o shape só por seguir jejum.

Abraços

[{..mAthEUs..} 4423]

Minha opinião sobre isso.

Como falaram ai (o Eduardo, não sei se mais alguem falou, não li tudo), para saúde o jejum seria melhor, mas para composição corporal não vai ter um impacto muito significante. Mas pra mim, na minha opinião e até que me provem o contrário, se é melhor pra saúde vai ser melhor pra composição corporal. Um corpo com melhor funcionamento consegue atingir objetivos de forma mais efetiva, mais rápida e ter efeitos mais duradouros.

Agora o tamanho disso na composição corporal já é outra história. A dificuldade de se obter dados em estudos são várias: o tempo de duração; o número de participantes; o controle; geralmente os estudos não tem tudo o que queremos, não tem todas as variaveis, todos os riscos que queremos pra tomarmos uma direção. O que se tem são vários estudos onde você vai captando as informações e, pela estatistica, chega a uma conclusão. Mas se os estudos não seguiram sempre um mesmo padrão, la no final o resultado vai ser diferente.

O que eu quero dizer com isso? É o seguinte.

Imaginemos que estamos em um avião com destino já traçado. Na metade do percurso, por algum motivo, pode ser uma turbulência, vento, distração do piloto, falha do co-piloto, esse avião sai um grau da rota.

Poxa, um grau não é nada perante o tamanho de um avião e o tamanho do céu, é algo insignificante, não é?

Mas agora imagine esse um grau daqui 1km se não for retomado o percurso. Daqui 2km ainda vai parecer algo pequeno, mas e daqui 500km? 1000km..

No final o destino vai ser completamente diferente do que tinha sido traçado, e isso por causa de apenas 1 grau, um pequeno grau que se for ver é algo imperceptível, algo muito insignificante.

Então pra quem está começando, tem muita massa pra ganhar ainda, tem muita gordura pra perder, talvez seja insignificante mesmo adotar estratégias como o jejum, por exemplo. Mas pra alguem que já está nessa estrada há um tempo, que já não tem tido os mesmos resultados de quando começou, já tem sentido a dificuldade de ganhar massa, de perder gordura, usar o jejum é uma ótima estratégia. Por que embora a curto prazo possa parecer que não faz diferença, isso é algo que a longo prazo você vai notar.

Não existem vários tipos de investimento? Existem aqueles a curto prazo, aqueles a longo prazo. Muitas vezes eles parecem ser iguais olhando a curto prazo, mas colocando em anos a diferença é absurda. Guarda 50 reais por mês em uma poupança; em um ano os juros vão ser insignificantes. Mas continue guardando durante 30 anos, você vai ver a diferença de rendimento. Vai ver que com os juros desse tempo todo você conseguiu planejar toda sua aposentadoria.

Com nosso corpo é a mesma coisa, existem investimentos que colhemos os frutos rapidamente e outros que vem com o tempo.

E como já disse, só a questão da saúde já compensa, e pra mim a saúde tem impacto direto na composição corporal, embora não seja um fator determinante. Um corpo em perfeito estado funciona melhor do que um com algum problema.

Abraço.

[Lucas, o Schrödinger 11998]

Minha opinião sobre isso.

Aí é que tá Matheus, na verdade uma alimentação mais frequênte provavelmente é superior - ainda que ligeiramente - pra composição corporal. O post abaixo tem um comentário do Brad sobre o assunto:

Segue post do Brad Schoenfeld no FB que coaduna com o que tenho dito aqui:

"More evidence that eating frequency does not substantially impact weight management. From the conclusion: "While it is unlikely that any 1 recommendation on eating frequency will be universally applicable, the most useful dietary advice regarding weight management for adults may be to focus on energy intake rather than eating frequency." With that said, it's important to point out that this is not necessarily applicable to those who are looking maximize muscle development and/or get down to very low body fat levels."

http://lm.facebook.com/l.php?u=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F25398748&h=VAQF4BGlx&enc=AZMurMRf7DbIuMhCtWCtTYHJPSRtGQLU-UCueCXeXR6L2bgptfw6kt3Z8dZG6Kvjd0w&s=1

Abaixo outro post em que eu falei sobre o assunto, cintando inclusive a a "janela" de 5-6h entre as refeições pré e pós treino para se otimizar hipertrofia encontrada em outra meta análise feita por Alan e Brad:

Achei que tava claro no texto. Não acho que a janela seja menor que 24h nem nada do tipo. Entretanto, caso se queira otimizar a hipertrofia - o que provavelmente é mais válidos pra profissionais -, o ideal é fazer 3-4 refeições ricas em proteína, inclusive com o pré e o pós treinos com um intervalo de no máximo 5-6h - isso segundo o Alan Aragon e o Brad Schoenfeld, que são top especialistas no assunto dieta e hipertrofia, sem contar que o Lyle McDonald tem uma visão bem parecida.

Enfim, acho importante deixar claro que gosto mto de jejum, faço uso quando posso, me traz um bem estar mto grande, enfim... Não sou contra, acho que é ótimo pra queima de gordura, mas não tão bom (mas, ainda assim, perfeitamente viável) pra ganho de massa muscular.

Abraço

Enfim, ao que os estudos e a posição desses especialistas (Alan Aragon, Brad Schoenfeld e Lyle McDonald, só pra citar os três nomes mais famosos) indicam, jejuns mto longos não são a melhor opção pra hipertrofia (grifei melhor, pois repito: é uma estratégia perfeitamente viável). Então, teoricamente, esse 1° na rota não seria pra melhor (lembrando que não estou levando em consideração aderência, que é um fator importantíssimo).

Abraços

Editado Agosto 25, 2015 às 16:02 por Shrödinger

[JulioSonic 307]

Na minha opinião, acho que só pela lógica, sem estudos sem nada, já da pra notar que apenas fazer jejuns não dará muita diferença pra composição corporal, é preciso ver a dieta com um todo. Tipo, a pessoa quer perder peso, ai faz o jejum num dia da semana e nos outros 6 come igual um porco rsrs

Meu objetivo principal é ganho de massa/hipertrofia, mas sempre com saúde. Fazer jejum com o esse tipo de objetivo é algo que na teoria não faria muito sentindo, principalmente porque meu bf é relativamente baixo por natureza. Mas pelos benefícios pra saúde, autofagia e tal, acabei aderindo a ele, ai para compensar, nos outros seis dias aumento minha ingestão calórica.

[Lucas, o Schrödinger 11998]

E pra tentar deixar mais claro ainda: todos esses especialistas (Brad, Alan, Lyle, Eric Helms...), bem como as diversas meta análises sobre o tema, afirmam que, caso a ingestão calórica e de proteínas sejam atingidas, o nutrient timing não fará diferença significativa. O significativo quer dizer: se vc não for um profissional, não adianta esquentar a cabeça com isso. Assim, a melhor dieta será aquela que melhor se adeque a sua saúde, rotina e preferências pessoas a longo prazo.