Intermitente 
Autor: Julio Cesar Tafforelli | Publicado: 2014-07-02T10:49:00-07:00


Intermittent Thoughts on Intermittent Fasting - The Fast #2: Health &amp; Longevity Effects of Intermittent Fasting







Intermittent Thoughts on Intermittent Fasting - The Fast #2: Health &amp; Longevity Effects of Intermittent Fasting










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Com ou sem os efeitos benéficos sobre marcadores de risco cardiovascular, a questão ainda permanece: "Pode jejum intermitente imitar o efeito da longevidade de restrição calórica, sem as ânsias constantes, fome constante e todos os tipos de" problemas humanos "que não vai mostrar em estudos sobre leveduras, vermes, roedores ou mesmo macacos (ver imagem 3)? "A fim de responder a esta pergunta, vamos primeiro tem que dar uma definição clara do que a nossa compreensão do jejum intermitente é, neste contexto, porque, obviamente, se acoplado a nossa (intermitente) rápido com aa restrição deliberada e grave calorias nós provavelmente acabar como Canto, o macaco do estudo longevidade na imagem 3 - antiga, mas miserável. O que nós queremos, por outro lado, é um jejum intermitente, onde - dentro da janela de alimentação - que é permitido comer à saciedade ... semelhante ao que estamos vendo em jejum religioso: não contagem de calorias e percebido (quando comparado com ) excessos normal de tamanhos de refeição. Agora, nós já sabemos a partir dos estudos citados acima (e em parcelas anteriores desta série) que, um mês em um regime dietético como que fornece benefícios consideráveis​​, tanto quanto a perda de peso, sensibilidade à insulina, as taxas de lipídios no sangue (! Isso é importante, porque é conhecedor o suficiente para dar af *** sobre o colesterol total e co) e marcadores inflamatórios, os quais estão associados não só a um aumento da expectativa de vida (Danaei. 2010), mas, mais importante, com um aumento da vida-qualidade e saúde neurológica (Bronwen. 2006) até as velhas (er) idades. A partir dos mesmos estudos, nós ainda sabemos também que quebrar o jejum, e retornando aos nossos hábitos alimentares antigos retorna estes marcadores à linha de base (cf. valores pós na figura 1). O que nós não sabemos, no entanto, é se ... &nbsp; Melhorias 1.intermediate em correlatos de saúde e longevidade como eles podem ser observados durante períodos intermitentes de Ramadã (intermitente) jejum fornecer qualquer, ou até mesmo benefícios significativos para a saúde a longo prazo, e &nbsp; 2.longterm (como em anos e décadas) jejum intermitente não iria mais de meses ou anos, perder o seu efeito, ou pior ainda, ser prejudicial para a nossa saúde em geral e, assim, reduzir a não estender a nossa expectativa de vida e / ou qualidade de vida A partir de estudos de roedores já sabemos que um protocolo de alimentação em dias alternados ao longo da vida aumenta expectativa de vida, na ausência de qualquer redução calórica (Goodrick. 1990;. Mattson, 2000). A prova de que os efeitos benéficos semelhantes, pelo menos na medida em que a mortalidade por doença crônica está em causa, poderia ocorrer em seres humanos vem de um estudo realizado em 2007 por Varaday e Hellerstein (Varaday. 2007), quem ainda observar que (como já apontado) "Mais pesquisas são necessárias para estabelecer definitivamente as conseqüências do ADF [dias alternados jejum]". A hipótese do relógio circadiano Um achado dos estudos dia de jejum alternativos que podem ser de importância primordial em vista de "qualidade de vida", aspecto, é o aumento do factor neurotrófico derivado do cérebro (BDNF), que tem sido observada em estudos em animais. O BDNF é envolvido no desenvolvimento do cérebro e da plasticidade e sua elevação induzida pelo jejum (intermitente) poderia explicar o efeito neuroprotector dos respectivos padrões de alimentação (Duran. 2001). Em uma revisão da literatura, Fory e Miskin se ainda observar que (Froy. 2010) [...] BDNF não poderia ser [diretamente] ligados aos efeitos neuro-protetor no cérebro de ratos restrição calórica, mas o aumento dos níveis de outro fator neurotrófico, fator derivado da linha de células da glia (GDNF), foram correlacionados com neuro-protecção de um modelo de primata de restrição calórica da doença de Parkinson. Curiosamente, o BDNF também é um componente da via de melanocortina do hipotálamo que controla a ingestão de alimentos e de peso corporal em ratos adultos, e que tem sido implicado na regulação do metabolismo energético. Afinal de contas, os cientistas acreditam que se exposições de peças ou até mesmo todos os seus efeitos por (re) definição de genes do relógio, uma hipótese que, apesar de ter os seus méritos ainda iria nos levar a considerações teóricas com pouco mérito aos nossos pensamentos "intermitentes" na resultados reais de jejum intermitente, que é por isso que vou, neste momento, avançar com os resultados de um estudo de 1999 sobre a relação de tamanho e redução do tecido adiposo dos mesmos para a longevidade. Não é de comer menos, mas apenas sobre a obtenção mais magro? Imagem 4: Quando estamos falando sobre os benefícios da perda de gordura corporal, isso, obviamente, não significa que você tem que entrar em Phil Heath Mr. Olympia '11 forma de viver mais tempo (foto bodybuilding.com) Nos parágrafos introdutórios deste parcela dos pensamentos intermitentes em séries jejum intermitente eu um pouco ridicularizou a idéia de mudar a vida inteira para se "rasgado e polido", agora, depois de revisitar alguns dos estudos e observar a estreita correlação de melhorias na metabólica marcadores de saúde, a redução da gordura corporal e consequentes efeitos do jejum (intermitente) de prolongar a vida, a questão central de Nir Barzilai de e 1999 papel de Gaurav Gupta Revisitando o Papel Fat Missa na life Extension Induzida por Restrição de Calorias parece de modo algum improvável: e se não é a inflamação e resistência à insulina e co que nos fazem gordura e reduzir nossas vidas, mas ser gordo que nos deixa resistentes à insulina, inflamado &amp; co e desta forma reduz nossa expectativa de vida? A resposta, de acordo com Barziilai e Gaurav, é simples (Barzilai. 1999): Na verdade, todos os benefícios de CR sobre o sistema neuroendócrino e aqueles relacionados com a melhoria na homeostase da glicose pode ser atribuída à diminuição em células adiposas e seus produtos. Provavelmente muito simples e acima de tudo, difícil de tratar com uma droga e, portanto, não é rentável o suficiente para ser aceito pelo estabelecimento médico. Agora, se este seria o caso, o jejum intermitente seria, de fato, proporcionar o procurado bala de prata para levar uma vida mais magro, mais saudável, já que ambos os relatos na rede, assim como a maioria dos estudos que têm sido citados neste, bem como as parcelas anteriores mostram bastante conclusivamente que ficar sem comer por períodos &lt;24h é capaz de reduzir as reservas de gordura do corpo, preservando o músculo magro (e osso) em massa. Mas por que, ou melhor como é que isso funciona? Jejum intermitente, redução de gordura, melhoria da saúde e da ciclicidade da vida Ilustração 1: Provavelmente é a interação mágica da AMPK e mTOR, que produz tais transformações notáveis ​​como Duong Nguyen da. Vamos aprofundar a sua interação recíproca na próxima edição dos Pensamentos intermitentes sobre jejum intermitente Series Devido à sua natureza cíclica jejum intermitente parece produzir temporariamente "reduções na síntese de proteínas" semelhantes (Barrows., 1978) como os que foram estabelecidos como os mecanismos fundamentais de os efeitos da restrição calórica prolonga a vida tão cedo como no final de 1970 e do qual sabemos hoje que, em parte, mediada por uma regulação negativa induzida pela AMPK da via mTOR. Em que, esta resposta AMPK transitória ao jejum intermitente, que fasters mais intermitentes ainda estimular exercitando em um estado (semi-) jejuou, parece ser profundo o suficiente para estimular ou, de acordo com uma pesquisa recente (cf. Canto. De 2010), que provavelmente deve dizer "sustentar" a SIRT1-caminho de uma forma que permite que pessoas a dieta para se beneficiar de seu efeito imediato, mobilizando gordura em adipócitos brancos (Picard. 2004) e sua capacidade de manter o comprimento do telômero (e longevidade posterior, cf. Palacios. 2010), sem os músculos de desperdício de efeitos colaterais indesejados de períodos de jejum prolongados. A expressão da AMPK induzida jejum é ainda apenas uma parte do ciclo, do qual nós aprendemos neste capítulo que é responsável tanto, os efeitos "cosméticas" na gordura corporal, o que pode, afinal, ser causador e não apenas corolário ou mesmo posterior a melhorias na sensibilidade à insulina (cf. o que vem primeiro: inflamação ou obesidade?), perfil lipídico, e toda a série de efeitos benéficos à saúde, que contribuem de forma irrefutável para o efeito de dietas longevidade desumanas de baixa caloria. Em vista do fato de que um outro valioso tarde de domingo está chegando ao fim, a discussão sobre o segundo jogador neste ciclo, o alvo da rapamicina em mamíferos, ou em suma mTOR, ainda vai ter que ser adiada para o próximo episódio da Intermitente Reflexões sobre jejum intermitente Series - então fique ligado, mantenha as perguntas e comentários que chegam e não se esqueça de verificar novamente na quinta-feira para ver o que AMPK e mTOR está fazendo para o nosso homem na cadeira de rodas nacionais de 2012, Adelfo Cerame!


















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﻿

Image 1: Any  roundworms reading this? I hope you know that by not eating enough and  feeling miserable you can extend your lifespan ;-)

Thanks Caenorhabditis elegans, or "C. elegans", almost everybody who is able to read a newspaper or online magazine will have heard of the miraculous effects of calorie restriction and fasting on longevity (of this worm!). Since I assume that you possess more gray matter than this transparent nematote, you will probably have asked yourself how, or  rather if these results from a worm with an average lifespan of 2-3  weeks translate to human beings,... well, all I can tell you is that  leading a miserable life of lifelong dieting appears to work in non-human primates, as well (Kemnitz. 2011). Now, the obvious question is:

How does all that relate to Intermitent Thoughts on Intermittent Fasting? Obviously, none of the roundworms or rhesus monkey's followed Martin Berkhan's intermittent fasting approach, did they? 
No, I have not seen pictures of abes on leangains.com, either, so I suppose they did not follow Berkhan's approach, but - and  this is the likewise fascinating, as well as surprising, connection -  there is scientific evidence that intermittent fasting could  reproduce some of the beneficial effects of caloric reduction while  avoiding a whole host of its undesirable side-effects. Reason enough for me, to devote this episode of the increasingly popular Intermittent Thoughts on Intermittent Fasting series to the non-cosmetic health effects of intermittent fasting (I know that's not as getting ripped and jacked, guys ;-)


Figure 1: Ramadan fasting leads to profound beneficial changes in inflammatory markers  (left) and blood lipids (right) in 20 healthy male non-obese volunteers  aged 23-39 (data calculated based on Aksungar. 2006)

We touched on one of this unsexy, yet vitally important health-benefits at the end of the last installment on the metabolic and endocrine effects of fasting, already: the beneficial effect on insulin resistance (as measured by a  +44% increase in the inverse of the long-term marker of insulin  resistance 1/HOMA-IR and the slight increase in QUICKI) Shariatpanahi et al. had observed in 55 ramadan fasting subjects (Shariatpanahi. 2008) for example constitutes one of these "boring side-effects", of which  many dieters fail to realize that improvements in insulin sensitivity or reductions in inflammatory markers and C-reactive protein (cf. figure  1, left), as they were reported by Aksungar et al. in a 2006 study on  the effects of religious "intermittent" fasting (Aksungar. 2006) facilitate weight - and more specifically - fat loss.



Image 2: Would  the issue of dehydration distort the results of Ramadan studies and thus render them irrelevant for our argumentation? (photo Offline Clinic)

As in almost every episode I want to make a few brief statements  regarding the "Ramadan model of intermittent fasting". I have already  discussed its advantages over "over-other day" or "alternative day"  fasting in the second installment of this  series and I have hinted at possible problems related to the restriction of water intake within the fasting period in the third installment of the series. Now, in view of the general recommendation to drink more and more frequently to avoid dehydration (USDA), it seems prudent to verify that potential beneficial health effects of  fasting are not masked by detrimental side effects of dehydration, if we - once again - want to rely on the available data on religious fasting  as part of our argumentation. In a paper published in the European Journal of Clinical Nutrition in 2003, Leiper, Molla and Molla report that despite the fact that  "[d]uring the daylight hours of Ramadan fasting, practising Muslims are  undoubtedly dehydrating", it is neither "clear whether they are  chronically hypohydrated" nor have there been any "detrimental effects  on health [...] directly attribut[able] to negative water balance at the levels that may be produced during Ramadan" observed in any  scientifically relevant studies (Leiper. 2003). It is thus relatively safe for us to assume that we can neglect he  influence of potential dehydration in our initial analysis of respective studies.

Now, what about the longevity effects? 



Image 3: The  effects the calorie restriction had on the ape on the right is certainly impressive, when you compare it to his 27.6 year old age-mate on the left - would be interesting to see how an  "intermittently fasted version would end up ;-) (img. from the Irish Medical Times)

With or without the beneficial effects on cardiovascular risk markers,  the question still remains: "Can intermittent fasting mimic the  longevity effect of calorie restriction without the constant  cravings, continuous hunger and all sorts of "human" problems that won't show in studies on yeast, worms, rodents or even apes (see image 3)?"

In order to answer this question, we will first have to give a clear cut definition of what our understanding of intermittent fasting is, in  this context, because, obviously, if we coupled our (intermittent) fast  with a a deliberate and severe calorie restriction we would probably end up like Canto, the ape from the the longevity study in image 3 - old,  but miserable. What we want, on the other hand, is an intermittent fast, where - within the feeding window - we are allowed to eat to satiety... similar to what we are seeing in religious fasting: no calorie counting and perceived (when compared to normal meal sizes) overeating.

Now, we do already know from the studies cited above (and in previous installments of this series) that one month on a dietary regimen like that provides considerable  benefits as far as weight loss, insulin sensitivity, blood lipid ratios  (! this is important, because we are knowledgeable enough to give a f*** about total cholesterol &amp; co) and inflammatory markers, all of  which are associated not only with an increased life-expectancy (Danaei. 2010), but, more importantly, with an increased life-quality and neurological health (Bronwen. 2006) up into the old(er) ages. From the same studies, we do yet also know that breaking the fast, and returning to our old dietary habits returns these markers to baseline (cf. post values in figure 1). What we do not know, however, is whether ...

intermediate improvements in correlates of health and longevity as  they can be observed during intermittent periods of Ramadan  (intermittent) fasting provide any, or even significant longterm health  benefits, and
longterm (as in for years and decades) intermittent fasting would  not over months or years lose its effect, or even worse, be detrimental  to our overall health and thus reduce not extend our life-expectancy  and/or life-quality

From rodent studies we already know that a life-long alternate-day feeding protocol increases lifespan in the absence of any caloric reduction (Goodrick. 1990; Mattson. 2000). Evidence that similar beneficial effects, at least as far as mortality  from chronic disease is concerned, would occur in human beings comes  from a 2007 study by Varaday and Hellerstein (Varaday. 2007), who do yet remark that (as I already pointed out) "more research is required to establish definitively the consequences of ADF [alternate day fasting]".

The circadian clock hypothesis 

A finding from alternative day fasting studies that may be of paramount  importance in view of the "quality of life"-aspect, is the increase in  brain-derived neurotropic factor (BDNF) that has been observed in animal studies. BDNF is involved in brain development and plasticity and its  (intermittent) fasting-induced elevation could explain the  neuroprotective effect of respective feeding patterns (Duran. 2001). In a review of the literature, Fory and Miskin do yet remark that (Froy. 2010)

[...] BDNF could not be [directly] linked to the neuro-protective effects                            in the brain of calorically restricted rats, but increased                            levels of another neurotrophic factor, glial cell line-derived factor (GDNF),                            were correlated with neuro-protection of a calorically restricted primate model                            of Parkinson's disease. Interestingly,                            BDNF is also a component of the hypothalamic melanocortin pathway that controls                            food intake and body weight in adult mice, and it                            has been implicated in the regulation of energy metabolism. 
After all, the scientists believe that IF exhibits part or even all of  its effects by (re-)setting clock genes, a hypothesis which despite  having its merits would yet lead us into theoretic considerations with  little merit to our "intermittent thoughts" on the real-world outcomes  of intermittent fasting, which is why I will, at this point, skip  forward to the results of a 1999 study into the relation of adipose  tissue size and reductions thereof to longevity.

Is it not about eating less, but just about getting leaner?



Image 4: When we  are talking about the benefits of losing body fat, this obviously does  not imply you have to get in Phil Heath Mr. Olympia '11 shape to live  longer (photo bodybuilding.com)

In the introductory paragraphs of this installment of the Intermittent Thoughts on Intermittent Fasting series I somewhat ridiculed the idea of changing one's whole life to get  "ripped and buffed", now, after revisiting some of the studies and  observing the close correlation of improvements in metabolic health  markers, reductions in body fat and consequent life-extending effects of (intermittent) fasting, the central question of Nir Barzilai's and  Gaurav Gupta's 1999 paper Revisiting the Role Fat Mass in the Life Extension Induced by Calorie Restriction seems by no means far fetched: What if ain't inflammation and insulin resistance &amp; co that make us fat  and reduce our lives, but being fat that leaves us insulin resistant,  inflammed &amp; co and thusly reduces our life-expectancy? The answer, according to Barziilai and Gaurav, is simple (Barzilai. 1999):

In fact, all of the benefits of CR on the neuroendocrine                     system and those related to the improvement in glucose homeostasis can be attributed to decrease in adipose cells and  their                     products.
Probably too simple and above all difficult to treat with a drug and  thus not profitable enough to be accepted by the medical establishment.  Now, if this would be the case, intermittent fasting would in fact  provide the sought-after silver bullet to leading a leaner, healthier  life, as both the anecdotal reports on the Net, as well as the the  majority of the studies that have been cited in this, as well as the  previous installments show quite conclusively that going without food  for periods &lt;24h is capable of reducing body fat stores, while preserving lean muscle (and bone) mass. But why, or better how does that work?

Intermittent fasting, fat reduction, health improvements and the cyclicality of life



Illustration 1: It probably is the magic interplay of AMPK and mTOR that produces such remarkable transformations as Duong Nguyen's. We will delve deeper into the their reciprocal interaction in the next installment of the Intermittent Thoughts on Intermittent Fasting Series

Due to its cyclic nature intermittent fasting seems to temporarily produce similar "reductions in protein synthesis" (Barrows. 1978) as the ones which have been established as the fundamental mechanisms  of the life-extending effects of calorie restriction as early as in the  late 1970s and of which we know today that they partly mediated by an  AMPK-induced downregulation of the mTOR pathway. In that, this transient AMPK response to intermittent fasting, which most intermittent fasters further stimulate by exercising in a (semi-)fasted state, appears to be profound enough  to stimulate or, according to some recent research (cf. Canto. 2010), we should probably say "sustain" the SIRT1-pathway to an extent that allows dieters to benefit from its immediate fat-mobilizing effect on white adipocytes (Picard. 2004) and its ability to maintain telomer length (and subsequent longevity, cf. Palacios. 2010) without the unwanted muscle-wasting side-effects of prolonged fasting periods.

The fasting induced AMPK expression is yet only one part of the cycle, of which we have learned in this installment that it is responsible for both, the "cosmetic" effects on body fat, which could, after all, be  causative and not just corollary or even subsequent to improvements in  insulin sensitivity (cf. What Comes First: Inflammation or Obesity?), lipid profiles, and the whole string of beneficial health effects which irrefutably contribute to the longevity effect of inhumane low-calorie  diets. In view of the fact that another valuable Sunday afternoon is  drawing to a close, the discussion of the second player in this cycle, the mammalian Target of Rapamycin, or in short mTOR, will yet have to be postponed to the next episode of the Intermittent Thoughts on Intermittent Fasting Series - so stay tuned, keep the questions and comments coming and don't  forget to check back on Thursday to see what AMPK and mTOR are doing to  our man at the 2012 wheelchair nationals, Adelfo Cerame!





﻿

Image 1: Any 
roundworms reading this? I hope you know that by not eating enough and 
feeling miserable you can extend your lifespan ;-)

Thanks Caenorhabditis elegans, or "C. elegans", almost everybody who is able to read a newspaper or online magazine will have heard of the miraculous effects of calorie restriction and fasting on longevity (of
 this worm!). Since I assume that you possess more gray matter than this
 transparent nematote, you will probably have asked yourself how, or 
rather if these results from a worm with an average lifespan of 2-3 
weeks translate to human beings,... well, all I can tell you is that 
leading a miserable life of lifelong dieting appears to work in non-human primates, as well (Kemnitz. 2011). Now, the obvious question is:

How does all that relate to Intermitent Thoughts on Intermittent Fasting? Obviously, none of the roundworms or rhesus monkey's followed Martin Berkhan's intermittent fasting approach, did they? 
No, I have not seen pictures of abes on leangains.com,
 either, so I suppose they did not follow Berkhan's approach, but - and 
this is the likewise fascinating, as well as surprising, connection - 
there is scientific evidence that intermittent fasting could 
reproduce some of the beneficial effects of caloric reduction while 
avoiding a whole host of its undesirable side-effects. Reason enough for
 me, to devote this episode of the increasingly popular Intermittent Thoughts on Intermittent Fasting series to the non-cosmetic health effects of intermittent fasting (I know that's not as getting ripped and jacked, guys ;-)


Figure 1: Ramadan
 fasting leads to profound beneficial changes in inflammatory markers 
(left) and blood lipids (right) in 20 healthy male non-obese volunteers 
aged 23-39 (data calculated based on Aksungar. 2006)

We touched on one of this unsexy, yet vitally important health-benefits at the end of the last installment on the metabolic and endocrine effects of fasting, already: the beneficial effect on insulin resistance (as measured by a 
+44% increase in the inverse of the long-term marker of insulin 
resistance 1/HOMA-IR and the slight increase in QUICKI) Shariatpanahi et al. had observed in 55 ramadan fasting subjects (Shariatpanahi. 2008)
 for example constitutes one of these "boring side-effects", of which 
many dieters fail to realize that improvements in insulin sensitivity or
 reductions in inflammatory markers and C-reactive protein (cf. figure 
1, left), as they were reported by Aksungar et al. in a 2006 study on 
the effects of religious "intermittent" fasting (Aksungar. 2006) facilitate weight - and more specifically - fat loss.



Image 2: Would 
the issue of dehydration distort the results of Ramadan studies and thus
 render them irrelevant for our argumentation? (photo Offline Clinic)

As in almost every episode I want to make a few brief statements 
regarding the "Ramadan model of intermittent fasting". I have already 
discussed its advantages over "over-other day" or "alternative day" 
fasting in the second installment of this 
series and I have hinted at possible problems related to the restriction
 of water intake within the fasting period in the third installment of the series. Now, in view of the general recommendation to drink more and more frequently to avoid dehydration (USDA),
 it seems prudent to verify that potential beneficial health effects of 
fasting are not masked by detrimental side effects of dehydration, if we
 - once again - want to rely on the available data on religious fasting 
as part of our argumentation. In a paper published in the European Journal of Clinical Nutrition in
 2003, Leiper, Molla and Molla report that despite the fact that 
"[d]uring the daylight hours of Ramadan fasting, practising Muslims are 
undoubtedly dehydrating", it is neither "clear whether they are 
chronically hypohydrated" nor have there been any "detrimental effects 
on health [...] directly attribut[able] to negative water balance at the
 levels that may be produced during Ramadan" observed in any 
scientifically relevant studies (Leiper. 2003).
 It is thus relatively safe for us to assume that we can neglect he 
influence of potential dehydration in our initial analysis of respective
 studies.

Now, what about the longevity effects? 



Image 3: The 
effects the calorie restriction had on the ape on the right is certainly
 impressive, when you compare it to his 27.6
year old age-mate on the left - would be interesting to see how an 
"intermittently fasted version would end up ;-) (img. from the Irish Medical Times)

With or without the beneficial effects on cardiovascular risk markers, 
the question still remains: "Can intermittent fasting mimic the 
longevity effect of calorie restriction without the constant 
cravings, continuous hunger and all sorts of "human" problems that won't
 show in studies on yeast, worms, rodents or even apes (see image 3)?"

In order to answer this question, we will first have to give a clear cut
 definition of what our understanding of intermittent fasting is, in 
this context, because, obviously, if we coupled our (intermittent) fast 
with a a deliberate and severe calorie restriction we would probably end
 up like Canto, the ape from the the longevity study in image 3 - old, 
but miserable. What we want, on the other hand, is an intermittent fast,
 where - within the feeding window - we are allowed to eat to satiety...
 similar to what we are seeing in religious fasting: no calorie counting
 and perceived (when compared to normal meal sizes) overeating.

Now, we do already know from the studies cited above (and in previous installments of this series)
 that one month on a dietary regimen like that provides considerable 
benefits as far as weight loss, insulin sensitivity, blood lipid ratios 
(! this is important, because we are knowledgeable enough to give a f***
 about total cholesterol &amp; co) and inflammatory markers, all of 
which are associated not only with an increased life-expectancy (Danaei. 2010), but, more importantly, with an increased life-quality and neurological health (Bronwen. 2006) up into the old(er) ages. From the same studies, we do yet also know that breaking the fast, and returning to our old dietary habits returns these markers to baseline (cf. post values in figure 1). What we do not know, however, is whether ...

intermediate improvements in correlates of health and longevity as 
they can be observed during intermittent periods of Ramadan 
(intermittent) fasting provide any, or even significant longterm health 
benefits, and
longterm (as in for years and decades) intermittent fasting would 
not over months or years lose its effect, or even worse, be detrimental 
to our overall health and thus reduce not extend our life-expectancy 
and/or life-quality

From rodent studies we already know that a life-long alternate-day feeding protocol increases lifespan in the absence of any caloric reduction (Goodrick. 1990; Mattson. 2000).
 Evidence that similar beneficial effects, at least as far as mortality 
from chronic disease is concerned, would occur in human beings comes 
from a 2007 study by Varaday and Hellerstein (Varaday. 2007), who do yet remark that (as I already pointed out) "more research is required to establish definitively the consequences of ADF [alternate day fasting]".

The circadian clock hypothesis 

A finding from alternative day fasting studies that may be of paramount 
importance in view of the "quality of life"-aspect, is the increase in 
brain-derived neurotropic factor (BDNF) that has been observed in animal
 studies. BDNF is involved in brain development and plasticity and its 
(intermittent) fasting-induced elevation could explain the 
neuroprotective effect of respective feeding patterns (Duran. 2001). In a review of the literature, Fory and Miskin do yet remark that (Froy. 2010)

[...] BDNF could not be [directly] linked to the neuro-protective effects
                            in the brain of calorically restricted rats, but increased
                            levels of another neurotrophic factor, glial cell line-derived factor (GDNF),
                            were correlated with neuro-protection of a calorically restricted primate model
                            of Parkinson's disease. Interestingly,
                            BDNF is also a component of the hypothalamic melanocortin pathway that controls
                            food intake and body weight in adult mice, and it
                            has been implicated in the regulation of energy metabolism. 
After all, the scientists believe that IF exhibits part or even all of 
its effects by (re-)setting clock genes, a hypothesis which despite 
having its merits would yet lead us into theoretic considerations with 
little merit to our "intermittent thoughts" on the real-world outcomes 
of intermittent fasting, which is why I will, at this point, skip 
forward to the results of a 1999 study into the relation of adipose 
tissue size and reductions thereof to longevity.

Is it not about eating less, but just about getting leaner?



Image 4: When we 
are talking about the benefits of losing body fat, this obviously does 
not imply you have to get in Phil Heath Mr. Olympia '11 shape to live 
longer (photo bodybuilding.com)

In the introductory paragraphs of this installment of the Intermittent Thoughts on Intermittent Fasting series
 I somewhat ridiculed the idea of changing one's whole life to get 
"ripped and buffed", now, after revisiting some of the studies and 
observing the close correlation of improvements in metabolic health 
markers, reductions in body fat and consequent life-extending effects of
 (intermittent) fasting, the central question of Nir Barzilai's and 
Gaurav Gupta's 1999 paper Revisiting the Role Fat Mass in the Life Extension Induced by Calorie Restriction seems by no means far fetched: What
 if ain't inflammation and insulin resistance &amp; co that make us fat 
and reduce our lives, but being fat that leaves us insulin resistant, 
inflammed &amp; co and thusly reduces our life-expectancy? The answer, according to Barziilai and Gaurav, is simple (Barzilai. 1999):

In fact, all of the benefits of CR on the neuroendocrine
                     system and those related to the improvement in 
glucose homeostasis can be attributed to decrease in adipose cells and 
their
                     products.
Probably too simple and above all difficult to treat with a drug and 
thus not profitable enough to be accepted by the medical establishment. 
Now, if this would be the case, intermittent fasting would in fact 
provide the sought-after silver bullet to leading a leaner, healthier 
life, as both the anecdotal reports on the Net, as well as the the 
majority of the studies that have been cited in this, as well as the 
previous installments show quite conclusively that going without food 
for periods &lt;24h is capable of reducing body fat stores, while preserving lean muscle (and bone) mass. But why, or better how does that work?

Intermittent fasting, fat reduction, health improvements and the cyclicality of life



Illustration 1: It probably is the magic interplay of AMPK and mTOR that produces such remarkable transformations as Duong Nguyen's. We will delve deeper into the their reciprocal interaction in the next installment of the Intermittent Thoughts on Intermittent Fasting Series

Due to its cyclic nature intermittent fasting seems to temporarily produce similar "reductions in protein synthesis" (Barrows. 1978)
 as the ones which have been established as the fundamental mechanisms 
of the life-extending effects of calorie restriction as early as in the 
late 1970s and of which we know today that they partly mediated by an 
AMPK-induced downregulation of the mTOR pathway. In that, this transient AMPK response to
 intermittent fasting, which most intermittent fasters further stimulate
 by exercising in a (semi-)fasted state, appears to be profound enough 
to stimulate or, according to some recent research (cf. Canto. 2010), we should probably say "sustain" the SIRT1-pathway to an extent that allows dieters to benefit from its immediate fat-mobilizing effect on white adipocytes (Picard. 2004) and its ability to maintain telomer length (and subsequent longevity, cf. Palacios. 2010) without the unwanted muscle-wasting side-effects of prolonged fasting periods.

The fasting induced AMPK expression is yet only one part of the cycle,
 of which we have learned in this installment that it is responsible for
 both, the "cosmetic" effects on body fat, which could, after all, be 
causative and not just corollary or even subsequent to improvements in 
insulin sensitivity (cf. What Comes First: Inflammation or Obesity?),
 lipid profiles, and the whole string of beneficial health effects which
 irrefutably contribute to the longevity effect of inhumane low-calorie 
diets. In view of the fact that another valuable Sunday afternoon is 
drawing to a close, the discussion of the second player in this cycle, the mammalian Target of Rapamycin, or in short mTOR, will yet have to be postponed to the next episode of the Intermittent Thoughts on Intermittent Fasting Series
 - so stay tuned, keep the questions and comments coming and don't 
forget to check back on Thursday to see what AMPK and mTOR are doing to 
our man at the 2012 wheelchair nationals, Adelfo Cerame!