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Intermittent Fasting: help me logic this article

Expatmommy79
Expatmommy79 Posts: 940 Member
edited March 2016 in Debate Club
So I am in a discussion about IF with another group. I said with calorie deficit and macros being the same, the Intermittent faster should not lose weight faster than the rest.

Then she presented this:
http://www.ncbi.nlm.nih.gov/m/pubmed/22608008/

Now what?! Was I wrong?
«1

Replies

  • senecarr
    senecarr Posts: 5,377 Member
    we subjected mice to either ad lib or time-restricted feeding (tRF) of a HFD for 8 hr per day.
    So... we let mice eat as much as they want, but some mice we let do this all day, and others we forced them only to do it during 8 hours. We found mice with access to food 24/7 got fatter.
    Okay, past the abstract, the claim is they normalized for body weight and that the energy intake was identical?
    Even assuming intake was identical, activity isn't. They mentioned that the ad libium mice are waking during the day to eat, and getting disturbed sleep pattern. I'd say that could explain their metabolic issues just as strongly as anything to do with feeding schedule.
  • Scamd83
    Scamd83 Posts: 808 Member
    There are mice getting ripped with IF?
  • yarwell
    yarwell Posts: 10,477 Member
    The time restricted (IF) mice had a higher metabolic rate on both diets according to Fig 1F, hence oxidised more of what they ate.
  • Yi5hedr3
    Yi5hedr3 Posts: 2,696 Member
    Yep, there's much more to it.
  • robertw486
    robertw486 Posts: 2,386 Member
    It might be worth doing more research on. I've seen human studies that suggest daily eating patterns do influence metabolic rate, including the metabolic rate increasing with extended periods of fasting within the 24 hour period. Overall the change isn't much, and won't matter much long term as far as weight control goes.

    I've actually noticed a change in heart rate as the interval between meals increases, and can be somewhat altered by my eating habits.
  • afrederick99
    afrederick99 Posts: 1 Member
    Just have them look up Jason Fung on YouTube. He is a medical doctor that reverses diabetes on real people with fasting regimens. His videos are amazing and shows proof with studies that fasting is really good for people.
  • Crisseyda
    Crisseyda Posts: 532 Member
    edited April 2016
    One thing that is happening here is the fasted mice are switching primarily to fat metabolism during the fast. When glucose stores get low, the mitochondria begin breaking down triglycerides instead of glucose for fuel, the krebs cycle becomes overwhelmed with ATP (since triglycerides create way more of it per molecule), and the ATP is diverted into the ketogenic pathway, creating ketone bodies. The average human will enter a state of mild ketosis when fasted 10-14 hrs.

    There are many many known benefits to ketosis, and I'm sure many more unknown. Fasting has been linked to longer lifespan in animal studies. This might be because there are unique enzymatic pathways activated during ketosis (be it from fasting or carbohydrate restriction), one of them called the sirtuins, which is a family of genes turned on by the mitochondria during fat metabolism and linked to longer lifespan. I think the suggested mechanism is that the mitochondria (which control cellular apoptosis) function more efficiently on fat metabolism (they do not produce the same amount of oxidative stress) and, therefore, do not destroy the cell as quickly. The question here is if fasting increases metabolic rate. I'm not sure of that, but it may benefit by the increased insulin sensitivity or the increased metabolic cost of gluconeogenesis during ketosis, among other metabolic changes.
  • stevencloser
    stevencloser Posts: 8,911 Member
    aqsylvester wrote: »
    One thing that is happening here is the fasted mice are switching primarily to fat metabolism during the fast. When glucose stores get low, the mitochondria begin breaking down triglycerides instead of glucose for fuel, the krebs cycle becomes overwhelmed with ATP (since triglycerides create way more of it per molecule), and the ATP is diverted into the ketogenic pathway, creating ketone bodies. The average human will enter a state of mild ketosis when fasted 10-14 hrs.

    There are many many known benefits to ketosis, and I'm sure many more unknown. Fasting has been linked to longer lifespan in animal studies. This might be because there are unique enzymatic pathways activated during ketosis (be it from fasting or carbohydrate restriction), one of them called the sirtuins, which is family of genes turned on by the mitochondria during fat metabolism and linked to longer lifespan. I think the suggested mechanism is that the mitochondria (which control cellular apoptosis) function more efficiently on fat metabolism (they do not produce the same amount of oxidative stress) and, therefore, do not destroy the cell as quickly. The question here is if fasting increases metabolic rate. I'm not sure of that, but it may benefit by the increased insulin sensitivity or the increased metabolic cost of gluconeogenesis during ketosis, among other metabolic changes.

    You're still wrong about how ketosis works.
  • Crisseyda
    Crisseyda Posts: 532 Member
    edited April 2016
    stevencloser wrote: »
    aqsylvester wrote: »
    One thing that is happening here is the fasted mice are switching primarily to fat metabolism during the fast. When glucose stores get low, the mitochondria begin breaking down triglycerides instead of glucose for fuel, the krebs cycle becomes overwhelmed with ATP (since triglycerides create way more of it per molecule), and the ATP is diverted into the ketogenic pathway, creating ketone bodies. The average human will enter a state of mild ketosis when fasted 10-14 hrs.

    There are many many known benefits to ketosis, and I'm sure many more unknown. Fasting has been linked to longer lifespan in animal studies. This might be because there are unique enzymatic pathways activated during ketosis (be it from fasting or carbohydrate restriction), one of them called the sirtuins, which is family of genes turned on by the mitochondria during fat metabolism and linked to longer lifespan. I think the suggested mechanism is that the mitochondria (which control cellular apoptosis) function more efficiently on fat metabolism (they do not produce the same amount of oxidative stress) and, therefore, do not destroy the cell as quickly. The question here is if fasting increases metabolic rate. I'm not sure of that, but it may benefit by the increased insulin sensitivity or the increased metabolic cost of gluconeogenesis during ketosis, among other metabolic changes.

    You're still wrong about how ketosis works.

    Steven, why don't you explain ketosis? And also explain how I'm "wrong about how ketosis works."
  • KarlynKeto
    KarlynKeto Posts: 323 Member
    aqsylvester wrote: »
    stevencloser wrote: »
    aqsylvester wrote: »
    One thing that is happening here is the fasted mice are switching primarily to fat metabolism during the fast. When glucose stores get low, the mitochondria begin breaking down triglycerides instead of glucose for fuel, the krebs cycle becomes overwhelmed with ATP (since triglycerides create way more of it per molecule), and the ATP is diverted into the ketogenic pathway, creating ketone bodies. The average human will enter a state of mild ketosis when fasted 10-14 hrs.

    There are many many known benefits to ketosis, and I'm sure many more unknown. Fasting has been linked to longer lifespan in animal studies. This might be because there are unique enzymatic pathways activated during ketosis (be it from fasting or carbohydrate restriction), one of them called the sirtuins, which is family of genes turned on by the mitochondria during fat metabolism and linked to longer lifespan. I think the suggested mechanism is that the mitochondria (which control cellular apoptosis) function more efficiently on fat metabolism (they do not produce the same amount of oxidative stress) and, therefore, do not destroy the cell as quickly. The question here is if fasting increases metabolic rate. I'm not sure of that, but it may benefit by the increased insulin sensitivity or the increased metabolic cost of gluconeogenesis during ketosis, among other metabolic changes.

    You're still wrong about how ketosis works.

    Steven, why don't you explain ketosis? And also explain how I'm "wrong about how ketosis works."

    Gotta to love the new 'like' buttons :wink: No idea why you are 'wrong', but you may want to Google 'gaslighting'. That's just my guess. (also, 'astroturfing')

  • 2snakeswoman
    2snakeswoman Posts: 655 Member
    I posted links to a study from a year or more back regarding weight loss in people who ate twice per day versus four times per day but the same calorie count. The people who ate twice per day averaged more weight loss. I can't recall the rationale.
  • Crisseyda
    Crisseyda Posts: 532 Member
    edited April 2016
    stevencloser wrote: »
    http://www.ncbi.nlm.nih.gov/books/NBK21190/
    http://sportsscientists.com/2010/01/exercise-and-weight-loss-part-3-fat/

    At rest you won't be using much of your glycogen, but instead fat for your energy needs. Glycogen is there for two reasons: keeping your blood sugar normal in between eating is your liver glycogen's job and fuelling intense exercise your muscle glycogen's. Your body doesn't just use it up all willy-nilly.
    Overnight is about the most at rest you ever are so the only glycogen you'll be using is going to be for keeping your blood sugar steady. You aren't going to use up all your liver glycogen during that time.
    Your glycogen doesn't get low, you're not gonna start producing any more ketones than usually and it's not ATP that's diverted into the ketogenic pathway to begin with anyway. ATP is the end product, usable for getting energy.
    Acetyl-CoA gotten from triglycerides gets turned to ketones in the liver because the necessary oxaloacetate for entering the krebs cycle to turn it into ATP is instead being used for gluconeogenesis when your glycogen stores are actually running low to keep you from going hypoglycemic.

    So to break down:
    You won't use up all your glycogen just overnight while sleeping
    You're always breaking down triglycerides for fuel, especially while you're at rest
    Your Krebs cycle is neither overwhlemed by ATP nor is it ATP that's creating ketones

    P.S. you have about 100-120 g of liver glycogen on average. That's up to 480 kcal or a good quarter of a whole day's worth of calories for a grown man. You don't use 50% of your energy from glucose during the 12-ish hours of mostly rest between your last meal and breakfast next day unless you're running a marathon at night.

    Yes, sorry, I meant Acetyl-CoA instead of ATP. Other than that, don't see anything else incorrect. The Krebs cycle is overwhelmed by Acetyl-CoA during fat metabolism.

    And I misunderstood that fasting cycles. I thought it was fasting every other day--confused it with a similar study I read. So maybe they aren't switching to fat metabolism, but at the very least, the study seems to suggest benefits to abstaining from caloric intake. Most who practice intermittent fasting would be doing so for at least 18 hrs, at which point, yes, they would be making ketones.

    That being said, I'm not sure what HFD entails. It may have therefore been low in carbohydrates.
  • stevencloser
    stevencloser Posts: 8,911 Member
    The krebs cycle is not overwhelmed by acetyl-coa. The oxaloacetate in the liver is used for something more important than the krebs cycle so the acetyl-coa can't even enter it. the acetyl-coa is instead turned to ketones to be transported elsewhere where it can be used.

    I'm doing intermittent fasting and the most common forms of it are 16 hours fasting (which is basically skipping breakfast) which I'm doing or 5:2 which is 5 days of normal maintenance eating with 2 days of low caloric intake with no rules for when to eat as far as I know.
    I can assure you I'm not creating any appreciable amount of ketones more than anyone who is eating their breakfast.
  • Crisseyda
    Crisseyda Posts: 532 Member
    stevencloser wrote: »
    The krebs cycle is not overwhelmed by acetyl-coa. The oxaloacetate in the liver is used for something more important than the krebs cycle so the acetyl-coa can't even enter it. the acetyl-coa is instead turned to ketones to be transported elsewhere where it can be used.

    I'm doing intermittent fasting and the most common forms of it are 16 hours fasting (which is basically skipping breakfast) which I'm doing or 5:2 which is 5 days of normal maintenance eating with 2 days of low caloric intake with no rules for when to eat as far as I know.
    I can assure you I'm not creating any appreciable amount of ketones more than anyone who is eating their breakfast.

    Ok, what is the "something more important"?

    And regardless of the details of the steps involved, the end result of fat metabolism is ketones if the average person is in mild ketosis within 10-14 hrs of fasting.
  • stevencloser
    stevencloser Posts: 8,911 Member
    edited April 2016
    Gluconeogenesis.
    Both the Krebs cycle and gluconeogenesis need the oxaloacetate, but in a state of glycogen depletion, gluconeogenesis is pretty much essential for survival to keep your blood sugar from tanking.

    And you're still wrong. The end result of fat metabolism is ATP.
    Body fat -> triglycerides
    triglycerides -> lipolysis -> fatty acids
    fatty acids -> beta oxidation -> Acetyl-CoA
    Acetyl-CoA -> Krebs Cycle -> ATP

    This works entirely without ketones.

    I haven't eaten in 11 hours now. And I'm not in mild Ketosis.
    Ketosis has a definition.
    Ketosis is when the amount of ketones in your urine rises due to increased production.
    It can be detected with test strips and the distinct smell, as well as the often experienced keto-flu as the brain which runs on mostly glucose needs to adjust to using ketones in higher amounts. This takes multiple days generally. You'd notice if your glycogen was almost empty.
  • robertw486
    robertw486 Posts: 2,386 Member
    stevencloser wrote: »
    http://www.ncbi.nlm.nih.gov/books/NBK21190/
    http://sportsscientists.com/2010/01/exercise-and-weight-loss-part-3-fat/

    At rest you won't be using much of your glycogen, but instead fat for your energy needs. Glycogen is there for two reasons: keeping your blood sugar normal in between eating is your liver glycogen's job and fuelling intense exercise your muscle glycogen's. Your body doesn't just use it up all willy-nilly.
    Overnight is about the most at rest you ever are so the only glycogen you'll be using is going to be for keeping your blood sugar steady. You aren't going to use up all your liver glycogen during that time.
    Your glycogen doesn't get low, you're not gonna start producing any more ketones than usually and it's not ATP that's diverted into the ketogenic pathway to begin with anyway. ATP is the end product, usable for getting energy.
    Acetyl-CoA gotten from triglycerides gets turned to ketones in the liver because the necessary oxaloacetate for entering the krebs cycle to turn it into ATP is instead being used for gluconeogenesis when your glycogen stores are actually running low to keep you from going hypoglycemic.

    So to break down:
    You won't use up all your glycogen just overnight while sleeping
    You're always breaking down triglycerides for fuel, especially while you're at rest
    Your Krebs cycle is neither overwhlemed by ATP nor is it ATP that's creating ketones

    P.S. you have about 100-120 g of liver glycogen on average. That's up to 480 kcal or a good quarter of a whole day's worth of calories for a grown man. You don't use 50% of your energy from glucose during the 12-ish hours of mostly rest between your last meal and breakfast next day unless you're running a marathon at night.

    I've been reading up on some of the keto adapted endurance people, and they defy this thinking. They stay in ketosis but still replenish glycogen stores by pushing the limits of staying in ketosis but yet "carb loading" in a slow methodical way before races and some training.

    I agree with the basics of your post, but have seen some stuff that leads me to think it's a bit more complex than stated. Those in keto retain glycogen stores, but the replenishment part of the picture gets blurry. But then again, replenishment of glycogen even in us carb eaters isn't really quick either, and can somewhat vary.
  • Crisseyda
    Crisseyda Posts: 532 Member
    edited April 2016
    stevencloser wrote: »
    Gluconeogenesis.
    Both the Krebs cycle and gluconeogenesis need the oxaloacetate, but in a state of glycogen depletion, gluconeogenesis is pretty much essential for survival to keep your blood sugar from tanking.

    And you're still wrong. The end result of fat metabolism is ATP.
    Body fat -> triglycerides
    triglycerides -> lipolysis -> fatty acids
    fatty acids -> beta oxidation -> Acetyl-CoA
    Acetyl-CoA -> Krebs Cycle -> ATP

    This works entirely without ketones.

    I haven't eaten in 11 hours now. And I'm not in mild Ketosis.
    Ketosis has a definition.
    Ketosis is when the amount of ketones in your urine rises due to increased production.
    It can be detected with test strips and the distinct smell, as well as the often experienced keto-flu as the brain which runs on mostly glucose needs to adjust to using ketones in higher amounts. This takes multiple days generally. You'd notice if your glycogen was almost empty.

    @stevencloser
    I understand your definition, but according to UpToDate, which is the evidence-based, peer-reviewed clinical decision resource that I use at my work, the average person will be in mild ketosis after 10-14 hrs of fasting, which equates to a blood ketoacid level of 1 mmol/L. I don't see any mention of the importance of diagnosis with urine ketostrips or any mention that this is the definition of ketosis.

    Also my understanding is if the amounts of acetyl-CoA challenge the processing capacity of the Krebs cycle (if activity in Krebs cycle is low due to low amounts of intermediates such as oxaloacetate), the acetyl-CoA is used instead to synthesize ketone bodies.

    If we know 1. that ketones have many metabolic and neurological benefits, 2. that they are instigated by fasting (or carbohydrate restriction), then I don't think it's a far leap to say 3. maybe some of these inexplicable benefits of fasting even for less than 24 hrs are related to the effect of ketones, i.e. ketosis, or the process by when they are created (which, for example, creates less oxidative stress, i.e. reactive oxygen species).
  • StealthHealth
    StealthHealth Posts: 2,417 Member
    I'm by no means an expert in this but recently spent a little time looking for any study which compared IF to "normal" eating protocols in humans.

    There were studies which showed that ad libium IF was a useful tool for weight loss (usually in obese subjects) where, presumably, IF simply generated a greater deficit than other protocols.

    I could find no studies in which the control and subject groups were fed isocalorifically except where they were specifically studying the effects on exercise performance (which wasn't what I was looking for at the time). Others may have more success?

    Going back to Mosley's 5:2 fast diet and re-reading the text and cross refs to studies, it seemed to me that the benefits that he was stating were at the least "on the generous side". I'm not saying I'm anti IF - It is a technique I use often, but rather that for me, it is a tool which helps me to adhere to my allotted calories.

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