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Thread: Intermittent Fasting - A Primer ( Part 1 )

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    Intermittent Fasting - A Primer ( Part 1 )

    This post has been a long time coming, and I've posted bits and pieces of it in various threads, but the amount of misunderstanding, misconceptions, and misinformation out there finally compelled me to put metaphorical pen to metaphorical paper here.

    First thing first, just to get it out of the way, intermittent fasting is not a miracle cure for all that ails you. I think that there is a lot there to recommend it to people, I practice my version of it, and have been at it for coming on three years now, and I fully intend to keep doing it. I do recognize, however, that it cannot be all things to all people. If anyone tries to tell you that one size fits all, then you are dealing with a blatant charlatan and you ought to govern yourself accordingly.

    What is intermittent fasting?

    There is no clear cut definition, unfortunately, which contributes to the misunderstandings. Wikipedia maintains that "Intermittent fasting (IF) is a pattern of eating that alternates between periods of fasting (usually meaning consumption of water only) and non-fasting." This definition is less than useless, as it practically suggests that eating the traditional three meals a day, and drinking water in between meals, which constitutes a pattern of eating alternating between fasting and non-fasting, is intermittent fasting.

    For my part, I suggest that we adopt a pragmatic definition: "intermittent fasting is a pattern of eating that involves a greater interval between meals than generally culturally prevalent." So, if you habitually skip breakfast, you are fasting intermittently by our definition. Skip breakfast and lunch? Great, you fit the bill too.

    One thing ought to be glaringly obvious in this definition due to its conspicuous absence: nobody said anything about calories. Should you choose to eat breakfast, lunch, and dinner all at 7:32 PM EST every day, then you are intermittently fasting by this definition. With that out of the way, we can dispell the first myth of IF - it is not starving. Starving yourself does fit within the definition, but it is a degenarate case. If you have some masochistic need to starve yourself and then call it IF, you certainly can, but the definition in no way requires it.

    Why would you fast intermittently? The Intuitive Answer.

    Going back to the intermittent fasting definition, at some point someone realized that to a large extent in modern society meals and meal times are culturally rather than biologically determined. It didn't always use to be that way, and we have the linguistic archeological record to prove it. The word breakfast (as said by Sean Connery, the best of the Bonds in my opinion) used to define a functional meal, the one that broke your fast, even if that were daily at 7:32 PM EST. In modern society, the word has been co-opted and transformed from a functional definition into a cultural one where breakfast is your morning meal, generally consumed before heading off to work. I expect that this arose as a consequence of industrialization given that factories thrive on predictability and conformity. It is not clear to me that people thrive on conformity to the factory whistle, a point most eloquently made by Connery's Bond who eats because he is hungry ( a biological imperative ), not because the time is appropriate for the meal ( a cultural imperative ). The question is then, what is an eating frequency that is compatible with a biological imperative?

    Another intuition that helps us answer the frequency question is the realization that there is a continuum of possible feeding schedules, and most of it represents ridiculous extremes. Assuming we are aiming at a 3000 kCal diet, and sleep for 8 hours a day, we could eat 0.05 kCal for the 57600 seconds that we are awake. That is, we could literally be constantly eating, albeit a miniscule amount of food each time. This represents a practical upper bound on how frequently one could eat. For a practical lower bound, consider attempting to eat a week's worth of food at one sitting, or 21000 kCal at one meal. Assuming that our diet consisted of the most energy dense food we know, dietary fat, we would need to eat 2.33 kg, or 5.1 lbs, of fat at this meal. Never mind the practical aspects of actually digesting this amount of fat, just the thought of attempting to do this is enough to revolt me. So, it would seem that a reasonable continuum has once a week at one end, and once a second at the other, with the true value probably being much more narrowly banded. I think enough of us know someone, or perhaps we are that someone, who does not eat breakfast because they do not feel hungry in the morning, even though they do not call that IF. Given this it is not much of a stretch to make the intuitive leap from not eating breakfast, to just eating dinner, as being a reasonable bit of the meal frequency continuum.

    Why would you fast intermittently? The Appeal to Authority Answer.

    Quick, name the first organized religion that comes to mind, and I'll bet you that they have a tradition of fasting. Whether Christian, Buddhist, Hindu, Muslim, or Jew, people have been fasting for better or worse for thousands of years now. I really don't have much to say about a religious justification for fasting, but I will say that in Islam, we have a population that fasts every year for the month of Ramadan, eating and drinking nothing between sunrise and sunset. Studying Muslim fasting populations allows scientist great insight into the effects of fasting on the human body, which brings us nicely to:

    Why would you fast intermittently? The Scientific / Metabolic Answer.

    One interesting aspect of fasting during Ramadan is that people tend to compress their eating schedule as the same quantitiy of food is ingested, but this is done in what amounts to one large meal in the evening. So, an interesting question to ask would be whether a greater interval between meals had any metabolic effect. It turns out that if you fast during Ramadan, you can expect:

    1. A decrease in LDL cholesterol, and a concomittant increase in HDL (as found in this study, as well as this one).
    2. A decrease in serum triglycerides ( same source as above. )
    3. No change in your plasma cortisol concentration.
    4. A pronounced lowering of insulin during the daily fast portion "favor[ing] a predominant lipolytic state."
    5. No change in thyroid hormone levels (T3, T4).
    6. Lowered levels of homocysteine and C-reactive protein ( indicators of inflamation ).
    7. You may experience some changes in body composition, but the studies are contradictory, although you are unlikely to gain weight.


    Like I said, fasting during Ramadan has been extensively studied, and I could go on, but I think you get the point. I have linked to all of the studies, but unfortunately, only some of them provide the full text. The remainder are just abstracts, but worth reading, all the same.

    In the above list, pay close attention to points 3, 4, and 5 because they relate to the hormonal impact of Ramadan fasting, and basically allow us to conclude that metabolically speaking, as far as the body is concerned, it's all business as usual, if not better. I make this point because invariably, when discussing intermittent fasting in the form of only eating one large meal in the evening, someone will start frantically beating the "starvation response" drum. You can politely ask them how eating a day's worth of calories in one meal can possibly constitute starvation, and then point them in the direction of the studies cited in 3, 4 and 5.

    For me, this is absolutely fascinating because all you have done is monkeyed about with the timing of your meals, and derived a pretty good benefit from it for your effort. It is almost as though you may have gotten something for nothing. Almost, but not quite. Even the most basic understanding of the digestive process must include the realization that not all the things you put in your mouth are good for you. Consequently, a large amount of digestive energy is expended in performing triage, separating the desirable aspects of our diet from the undesirable, assimilating the good bits, and disposing of the bad. It would seem plausible that the observed benefits of Ramadan fasting might be due to the fact that the body is not continuously engaging in this metabolically taxing process throughout the day, but rather doing it all in one concentrated batch.

    In the interest of full disclosure, I do not follow Ramadan style fasting insofar as I find the proscription on drinking during the day too strict. I understand that this means that the conclusions reached in the studies I referenced therefore may not apply to me, as the observed effects may be due to the drinking behaviour in conjunction with the eating. I don't believe that this is the case, but my beliefs do not seem to affect objective reality, much to my consternation.

    As I think I am nearing the 10000 character limit for a post, and as this seems a good place to pause, I'll let you digest and give my cramping fingers a break.

    Stay tuned for part 2 ...

    -PK

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    Quote Originally Posted by pklopp View Post
    ..
    In the above list, pay close attention to points 3, 4, and 5 because they relate to the hormonal impact of Ramadan fasting, and basically allow us to conclude that metabolically speaking, as far as the body is concerned, it's all business as usual, if not better. I make this point because invariably, when discussing intermittent fasting in the form of only eating one large meal in the evening, someone will start frantically beating the "starvation response" drum. You can politely ask them how eating a day's worth of calories in one meal can possibly constitute starvation, and then point them in the direction of the studies cited in 3, 4 and 5.

    ..
    This looks somewhat familiar since I asked a similar question about 2 days ago, but it wasn't about missing a single meal. My question was just about do the proponents of IF take rT3 into account or not? Your list has T3 and T4. Unless I don't understand the starvation response correctly, the hormone you want to know about is rT3 (reverse T3) not T3 or T4.

    It could very well be that IF, as practiced, typically does not include enough time for rT3 to elevate and become an issue. It could be. But just based on the responses I have seen in the past few days, it has raised my suspicions as far as is anyone really paying attention? I just don't see it yet. People are dismissing the question or appealing to authority ("smart people say do it so just shut up..etc"). The question could easily be closed by a single reference to a single study where rT3 was taken into account and found to not be an issue.

    Just thinking about it with a Grok hat on, one would think that even 24 hrs here and there would not send one's hormones into a permanent tailspin. But I'm just guessing. I just want to see some numbers, or know that people advocating this know enough to pay attention and get numbers. So far it does not seem to be the case.

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    Quote Originally Posted by DFH View Post
    This looks somewhat familiar since I asked a similar question about 2 days ago, but it wasn't about missing a single meal. My question was just about do the proponents of IF take rT3 into account or not? Your list has T3 and T4. Unless I don't understand the starvation response correctly, the hormone you want to know about is rT3 (reverse T3) not T3 or T4.
    A few things to note, as I alluded to in the initial post, IF is not well defined. I don't know what you mean when you say intermittent fasting. For the sake of this initial post, I will be dealing specifically with IF more or less styled on the Ramadan model, with the notable inclusion of drinking non caloric beverages throughout the fast. This allows me to refer to the relatively large body of research out there on the topic.

    None of the studies that I've see address rT3. However, what I've been able to glean about rT3 from Wikipedia goes along this line ( emphasis mine ):

    ...rT3, unlike T3, does not stimulate thyroid hormone receptors. However, rT3 binds to these receptors, thereby blocking the action of T3. Under stress conditions, the adrenal glands produce excess amounts of cortisol. Cortisol inhibits the conversion of T4 to T3, thus shunting T4 conversion from T3 towards rT3.
    Assuming that the metabolic pathway is as described, then, we do have an indication that Ramadan style fasting does not disturb cortisol metabolism, hence, we can conclude that T4 conversion to T3 won't be inhibited, and therefore no additional rT3 will result.

    Take a look at this chart showing the 24h cortisol levels of subjects before, during, and after Ramadan fasting and you will see that they are all very similar. In fact, at the conclusion of Ramadan, it looks like the area under the curve for cortisol is actually less than 2 days prior to starting the fast!



    Of course, all of this assumes that your metabolism is healthy. The chart just says that the fast is not a particular stressor on subjects. I doesn't say that they weren't producing bucket loads of rT3. Rather, it is indicative of the fact that subjects were probably converting T4 to rT3 at the same rate as prior to the fast. If you are not healthy, all bets are off, and the most ordinarily benign of things could cause you serious harm ( think severe peanut allergies here for an example ).

    -PK

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    DFH, I referenced this earlier:

    "Composition of the diet rather than reduction in the total calorie intake seems to determine the occurrence of decreased T3 generation in peripheral tissues during food deprivation. The dietary content of carbohydrate appears to be the key ingredient since as little as 50 g glucose reverses toward normal the fast-induced changes in T3 and rT3.52 Refeeding of protein may partially improve the rate of T3 generation, but the protein may be acting as a source of glucose through gluconeogenesis.54 Yet, dietary glucose is not the sole agent responsible for all changes in iodothyronine metabolism associated with starvation.For example, the increase in serum rT3 concentration may not be solely dependent on carbohydrate deprivation since a pure protein diet partially restores the level of rT3 but not that of T3 39 (Fig. 5-1). The Non-Thyroidal Illness Syndrome - Chapter 5b : Thyroid Disease Manager | Thyroid Disease | ThyroidManager.org

    It seems to me that possible rT3 issues can be mitigated by eating adequate amounts of carbohydrates as well as protein before/after fasting and/or in the eating window.. While I think long term undereating and/or VLC can inhibit thyroid function, I do not see using "eating windows" or intermittent fasting being globally harmful. I do believe that intermittent fasting, for people with known rT3 issues, should be weighed carefully with input from their physician.

    See also:
    SERUM LEVELS OF T4, T3, REVERSE T3, 3,3[]-DIIODOTHYRONINE AND 3[],5[]-DIIODOTHYRONINE IN OBESITY, BEFORE AND AFTER JEJUNO-ILEAL BYPASS - FABER - 2008 - Clinical Endocrinology - Wiley Online Library

    ScienceDirect - Metabolism : Nature of suppressed TSH secretion during undernutrition: Effect of fasting and refeeding on TSH responses to prolonged TRH infusions

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    Quote Originally Posted by marcadav View Post
    It seems to me that possible rT3 issues can be mitigated by eating adequate amounts of carbohydrates as well as protein before/after fasting and/or in the eating window
    I found this really interesting, not because I know anything about rT3, but because I've just posted in my journal that I've found I crash after a 19 hour fast if I don't include starches in my break-fast. N=1 and all that, but without the kumara or similar, I just feel shaky and starving no matter how good I feel while I'm still fasting.
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    Quote Originally Posted by marcadav View Post
    DFH, I referenced this earlier:

    "Composition of the diet rather than reduction in the total calorie intake seems to determine the occurrence of decreased T3 generation in peripheral tissues during food deprivation. The dietary content of carbohydrate appears to be the key ingredient since as little as 50 g glucose reverses toward normal the fast-induced changes in T3 and rT3.52 Refeeding of protein may partially improve the rate of T3 generation, but the protein may be acting as a source of glucose through gluconeogenesis.54 Yet, dietary glucose is not the sole agent responsible for all changes in iodothyronine metabolism associated with starvation.
    I feel that we are talking at cross purposes. You may not be expressly aware of it, but we are actually discussing hormesis here, the term for generally-favorable biological responses to low exposures to toxins and other stressors. A pollutant or toxin showing hormesis thus has the opposite effect in small doses as in large doses.

    As you can see in the graph below, for any arbitrary "stressor" or substance, there is a band where that substance is stimulatory to the organism, and pretty much harmful at lower or higher doses. This is hormesis in action. If you don't like Greek, you can think of this as the Goldilocks principle, there is a dose range that is "just right!", which I propose to call the efficient frontier:



    Before we get too lost in dry academic language here, let me put "stressor" into context. Let's consider that even one of the most fundamental constituents of our bodies, water, exhibits hormesis and an efficient frontier. We all know that without water for just a few days, we will die. Drink too much water, and you will die due to acute water intoxication. Get the right amount of water and you will thrive.

    And this is where our paths diverge. I keep trying to answer the question "What is the range for meal frequency where we can thrive?" and replies are coming back with "What happens when you push the meal frequency to the extreme right in the hormesis graph?" To answer that question, I actually don't need to reference any study, because I can just go back to the principle of hormesis for the answer. It may be a tautology, but here goes "when you leave the efficient frontier of the hormesis graph, the stressor will cause damage to the organism, perhaps catastrophically so."

    Nevertheless, there is work to do here. So, the initial quote above while interesting immediately raises some flags that I would want to investigate. I've highlighted the problematic issues in bold, and it essentially boils down to what did the authors of that original paper actually study? What is hiding behind the phrase "food deprivation?" How many calories? How often? For how many days? The fact that they refer to iodothyronine metabolism during "starvation" makes me suspect that we are looking at prolonged periods without food, much in excess of 48 - 72 hours, and more than likely beyond the efficient frontier for meal frequency. Without access to the full study, however, I cannot do anything but speculate at this point.

    This is a pretty good reference, mostly because we have access to the full text of the study, so we can determine whether it applies here, or not. It does not because it addresses the effects of fasting over 10 days, which I believe is beyond the efficient frontier and definitely into potential starvation.

    I'm not going to expressly look at this study, for lack of time, I may come back to it later. I will say, however, that it addresses an unhealthy population subsegment, those that have needed surgical intervention to address their problems. As such, I would be extremely cautious in drawing any conclusions from it if you do not belong to the same population as those under study ( ie individuals with a jejuno-ileal bypass )

    I do not see using "eating windows" or intermittent fasting being globally harmful. I do believe that intermittent fasting, for people with known rT3 issues, should be weighed carefully with input from their physician.
    +1000

    We are in violent agreement here. If you are not healthy, particularly with respect to your thyroid metabolism, see your doctor before doing things which will impact on thyroid metabolism. Fasting will impact thyroid metabolism. This is natural and expected. If fasting does not impact thyroid metabolism, that in itself is a pathological condition.

    Maybe I may have time later to look at this...

    -PK

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    Quote Originally Posted by DFH View Post
    It could very well be that IF, as practiced, typically does not include enough time for rT3 to elevate and become an issue. It could be. But just based on the responses I have seen in the past few days, it has raised my suspicions as far as is anyone really paying attention? I just don't see it yet. People are dismissing the question or appealing to authority ("smart people say do it so just shut up..etc"). The question could easily be closed by a single reference to a single study where rT3 was taken into account and found to not be an issue.
    PK, This was what I was responding to. I was providing references to help DFH see what happens in respect to rt3.

    If increased rT3, in connection to food deprivation and starvation "reverses toward normal the fast-induced changes in T3 and rT3" with 50 grams of glucose and/or protein refeeds, then any possible rT3 issues during IF--which is not deprivation or starvation--would be mitigated by the same pathway outlined in the quote.

    IMO, the other studies provided support rT3 improvement with refeeds following calorie restriction and/or undernutrition.

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    Quote Originally Posted by marcadav View Post
    PK, This was what I was responding to. I was providing references to help DFH see what happens in respect to rt3.

    If increased rT3, in connection to food deprivation and starvation "reverses toward normal the fast-induced changes in T3 and rT3" with 50 grams of glucose and/or protein refeeds, then any possible rT3 issues during IF--which is not deprivation or starvation--would be mitigated by the same pathway outlined in the quote.

    IMO, the other studies provided support rT3 improvement with refeeds following calorie restriction and/or undernutrition.
    Oh, I see ... roger that, then!

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    Quote Originally Posted by pklopp View Post
    what did the authors of that original paper actually study? What is hiding behind the phrase "food deprivation?" How many calories? How often? For how many days? The fact that they refer to iodothyronine metabolism during "starvation" makes me suspect that we are looking at prolonged periods without food, much in excess of 48 - 72 hours, and more than likely beyond the efficient frontier for meal frequency. Without access to the full study, however, I cannot do anything but speculate at this point.
    Would you like me to try and get hold of the original study? I'm not sure which one you're referring to, so if you send me the details I'll give it a try.
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    Quote Originally Posted by Jac View Post
    Would you like me to try and get hold of the original study? I'm not sure which one you're referring to, so if you send me the details I'll give it a try.
    I would definitely welcome the help in tracking that study down, please!

    I'm not sure how much luck you will have, though. Here is where that came from. It looks to be an online book, and I don't know whether they actually have the data and methodology backing the conclusions. Maybe the principals behind that website might be able to dig up the data?

    -PK

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