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Intermittent Fasting: help me logic this article

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  • stevencloserstevencloser Posts: 8,917Member Member Posts: 8,917Member Member
    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).

    You always have an amount of ketone bodies in your blood, fasting or not. The normal concentration is that 1 mmol/l and is undetectable by Rothera's test, which is the standard test to check if you're in ketosis.
  • CrisseydaCrisseyda Posts: 532Member Member Posts: 532Member Member
    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).

    You always have an amount of ketone bodies in your blood, fasting or not. The normal concentration is that 1 mmol/l and is undetectable by Rothera's test, which is the standard test to check if you're in ketosis.

    You are incorrect. 1 mmol/L is not negative/normal baseline. A ketoacid blood level of > 0.6 mmol/L equates to a negative urine test; a blood ketoacid level of 0.6 - 1.5 mmol/L equates to small to moderate urine ketone reading. Blood and urine ketone tests do not always agree because urine could have been sitting in the bladder for many hours, but a blood ketone test is far more accurate.
  • sijomialsijomial Posts: 15,521Member Member Posts: 15,521Member 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.
    @StealthHealth
    I did 5:2 and found it a great adherence tool but do agree that Michael Mosley seems to have done some cherry picking and made some assumptions/conclusions not really backed by, or taken out of context, from the various studies referenced.

    If you are interested would suggest looking for the work by Dr Krista Varady who carried out a far more scientific studies/research on ADF.
    She actually had a bit of an issue with Mosley and insisted her studies were removed from later print runs of The Fast Diet.
  • StealthHealthStealthHealth Posts: 2,418Member Member Posts: 2,418Member Member
    sijomial wrote: »
    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.
    @StealthHealth
    I did 5:2 and found it a great adherence tool but do agree that Michael Mosley seems to have done some cherry picking and made some assumptions/conclusions not really backed by, or taken out of context, from the various studies referenced.

    If you are interested would suggest looking for the work by Dr Krista Varady who carried out a far more scientific studies/research on ADF.
    She actually had a bit of an issue with Mosley and insisted her studies were removed from later print runs of The Fast Diet.

    Thanks for that. I'll look into her work (I've heard of her and I think, I may have seen her on TV or a YouTube vid but not sure).
  • yarwellyarwell Posts: 10,573Member Member Posts: 10,573Member Member
    Ketosis has a definition.
    Ketosis is when the amount of ketones in your urine rises due to increased production.

    You appear to be defining ketonuria. This may or may not occur when there are ketones in the blood.

    Ketosis is more usually defined by elevated levels of ketones in the blood, which needs a test meter or a lab.

    I would agree that there aren't many ketones around in overnight fasted people on a normal carbohydrate diet, this can be seen in the baseline fasted characteristics of any study that measures ketones in blood.
    edited April 2016
  • yarwellyarwell Posts: 10,573Member Member Posts: 10,573Member Member
    [
    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.

    In http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2548350/pdf/JAMMC-23-069.pdf the average in overnight fasted hospitalised children was 0.17 mmol/l B-OHB in serum. Acetoacetate levels were about half that.

    http://www.clinsci.org/content/ppclinsci/81/2/189.full.pdf also shows low baseline levels :-

    33ad5hdbvtwr.png
  • CrisseydaCrisseyda Posts: 532Member Member Posts: 532Member Member
    @stevencloser

    According to this talk by Mark Mattson (Chief of the Laboratory of Neurosciences at the National Institute on Aging and professor of Neuroscience at The Johns Hopkins University), if you go to 7:05, he mentions the 8-hr diet, where one restricts energy intake to an 8 hr window, which he says is long enough to shift energy metabolism to fat and get the benefits of ketones.



    He also mentions that it takes 10-12 hrs before you deplete the glycogen stores in your liver, faster if you exercise, and shift into ketosis... which also aligns well with what I read in UpToDate.

    According to Mark Mattson, IF is not just about eating less calories and losing weight. He mentions their research finding an increase in brain derived neurotrophic factors which help increase the number of mitochonidria in nerve cells, thereby increasing learning and memory ability.

    So, yeah... I'm not the only one who has thought this. And I'm kinda biased toward peer-reviewed databases and Johns Hopkins professors.

    [edited by MFP Moderator]
    edited April 2016
  • stevencloserstevencloser Posts: 8,917Member Member Posts: 8,917Member Member
    @stevencloser

    According to this talk by Mark Mattson (Chief of the Laboratory of Neurosciences at the National Institute on Aging and professor of Neuroscience at The Johns Hopkins University), if you go to 7:05, he mentions the 8-hr diet, where one restricts energy intake to an 8 hr window, which he says is long enough to shift energy metabolism to fat and get the benefits of ketones.



    He also mentions that it takes 10-12 hrs before you deplete the glycogen stores in your liver, faster if you exercise, and shift into ketosis... which also aligns well with what I read in UpToDate.

    According to Mark Mattson, IF is not just about eating less calories and losing weight. He mentions their research finding an increase in brain derived neurotrophic factors which help increase the number of mitochonidria in nerve cells, thereby increasing learning and memory ability.

    So, yeah... I'm not the only one who has thought this. And I'm kinda biased toward peer-reviewed databases and Johns Hopkins professors.

    [edited by MFP Moderator]

    It may be 10-12 hours from the moment it starts to utilize it.
    That is however not 10-12 hours after you last ate unless your meal didn't contain any carbs itself.
  • stevencloserstevencloser Posts: 8,917Member Member Posts: 8,917Member Member
    yarwell wrote: »
    [
    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.

    In http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2548350/pdf/JAMMC-23-069.pdf the average in overnight fasted hospitalised children was 0.17 mmol/l B-OHB in serum. Acetoacetate levels were about half that.

    http://www.clinsci.org/content/ppclinsci/81/2/189.full.pdf also shows low baseline levels :-

    33ad5hdbvtwr.png

    The question is, would you call this state "mild ketosis"?
  • yarwellyarwell Posts: 10,573Member Member Posts: 10,573Member Member
    No I would not call 0.1 mmol mild ketosis, not least because it's the first notch on most measures. 0.5 or above to count in my view, below that the ketone uptake flux is too low to bother about.
  • yarwellyarwell Posts: 10,573Member Member Posts: 10,573Member Member
    they read zero too, or at least mine does. Quite often in fact.
  • broseidonkingofbroceanbroseidonkingofbrocean Posts: 181Member, Premium Member Posts: 181Member, Premium Member
    I don't think scientific study proves IF being that beneficial in humans and the benefit is just being in a deficit. However I do use IF and it helps me out when I start a cut and it has produced results for many others who had trouble with a regular diet. With any diet give it a try and see if it works for you. Everyone thinks their diet is the best one but the best diet for you is whatever diet works for you.
    edited April 2016
  • yarwellyarwell Posts: 10,573Member Member Posts: 10,573Member Member
    shell1005 wrote: »
    yarwell wrote: »
    they read zero too, or at least mine does. Quite often in fact.

    Well then you use a different meter then the one that they used at the research hospital. 0.1 mmol was the lowest it registered.

    Either that or someone was making stuff up. Can't say I've met many (any ?) lab instruments of any sort where you can't zero them with distilled water as part of calibration. Obviously 0.1 is the lowest non-zero reading if it only does 1 decimal place but I'm not convinced despite the appeal to authority.
  • CrisseydaCrisseyda Posts: 532Member Member Posts: 532Member Member
    I said that 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.

    @stevencloser showed a study where children fasted overnight had blood ketoacid of 0.1 mmol/L? So... when we fast our patients overnight for procedures, the standard start time is midnight--that's pretty late to start a 10-14 fast. Midnight is pretty universal, and actually when I worked at a pediatric hospital there was even more leeway because children get cranky! So how long were those kids fasted? And how many kids were there in the sample size? I realize you're trying to disprove UpToDate for some reason. You're incredulous to believe that people can switch to fat metabolism so quickly or that they start to create ketones that quickly after switching to fat metabolism.
  • stevencloserstevencloser Posts: 8,917Member Member Posts: 8,917Member Member
    Yarwell did, not me.

    Btw. I found where the problem was. Wiki used mg/dl so I googled how that converts to mmol/L and it said they're interchangable, when actually 1 mg/dl is 0.1 mmol/l.
    So yeah, normal amounts in people not in ketosis are 0.1-0.2 mmol/l.

    According to yarwell's source, overnight concentration of ketones is not increased.

    Wikipedia defines Ketosis starting at 0.5 mmol/l but calls the range between the 0.2 and 0.5 "mild ketosis".

    When in a severe deficit additionally (from e.g. starving) concentration reaches 3-5 and people suffering from ketoacidiosis go above 12.
    http://srmuniv.ac.in/sites/default/files/files/KETONEBODYMETABOLISM.pdf (page 36)
  • lemurcat12lemurcat12 Posts: 30,886Member Member Posts: 30,886Member Member
    Yarwell did, not me.

    I was just about to point this out. As for the question about the length of the fast, the study Yarwell linked addressed that too -- 12 hours.
  • CrisseydaCrisseyda Posts: 532Member Member Posts: 532Member Member
    FASTING KETOSIS — The hepatic generation of ketone bodies described in the preceding paragraph is the normal physiologic response to fasting. Mild ketosis (ketoacid concentration of about 1 mmol/L) generally develops after a 12- to 14-hour fast. If fasting continues, the ketoacid concentration continues to rise and peaks after 20 to 30 days at a concentration of 8 to 10 mmol/L (mmol/L is used here rather than meq/L since meq/L does not apply to acetone, which has no charge). Beta-hydroxybutyrate is the major ketone body that accumulates [3-5].

    3. Reichard GA Jr, Owen OE, Haff AC, et al. Ketone-body production and oxidation in fasting obese humans. J Clin Invest 1974; 53:508.
    4. Cahill GF Jr. Fuel metabolism in starvation. Annu Rev Nutr 2006; 26:1.
    5. Owen OE, Caprio S, Reichard GA Jr, et al. Ketosis of starvation: a revisit and new perspectives. Clin Endocrinol Metab 1983; 12:359.

    From UpToDate
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