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Leptin: It probably doesn't do what you think it does.

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  • Leptin: It probably doesn't do what you think it does.

    Those of you that recall my posts on intermittent fasting know what you are in for with this, but for those of you that don't : it is going to be long, probably multi-part, but hopefully worth your time.

    What This Post Is Not

    I am not going to directly address the myriad of posts that appear in the forum regarding the successes that people have had following a "leptin reset" diet. I am sure that all of you that have posted to this effect are sincere, and further, I am glad that you have experienced success in your quest for a better you. My purpose is to determine, to the extent that I can, whether these successes can be at all attributed to the action of leptin, or to some other fundamental factor.

    Argument from Analogy

    Leptin is interesting to both scientists and lay people because it is secreted exclusively by adipose tissue in direct proportion to adipose fat mass. Further, leptin has profound effects in the brain, not the least of which is that in those individuals that lack functioning leptin or leptin receptors, the result is a voracious appetite, lowered metabolic rate, and an attendant acretion of adipose fat mass. Administering recombinant leptin in cases of leptin deficiency results in a decrease in appetite, increased metabolic rate, and weightloss. This has led many to conceive of leptin as the fuel gauge of the body, conveying long term energy status information to the brain, which will then modify metabolism accordingly.

    Most of us in have at least a passing familiarity with cars which brings with it a pretty good understanding of how a fuel gauge works. If we're speaking of a late model car, then the fuel monitoring system consists of a sensor located in the gas tank, a gauge in the dashboard to indicate fuel levels to the driver, and most often, a warning light that illuminates when fuel levels drop dangerously low and serves to draw the drivers attention to that fact so appropriate action can be taken. Using this as the base analogy for how the leptin feedback system works in metabolism actually turns out to be quite useful.

    Consider those occasions when you were driving and the fuel warning light illuminated. I am quite confident in asserting that your normal behaviour changed, and you immediately started looking for the nearest gas station. This situation, analogous to metabolically low circulating leptin levels, resulted in an increase in your awareness / appetite for gasoline. Further, your gasoline consumption rate ( metabolic rate ) was lowered as you presumably didn't accelerate as vigorously as you otherwise might, you began coasting rather than applying the brakes, and maybe even tried timing lights to avoid having to stop and then accelerate from a standstill. Once you fed your car with gasoline, you reverted to your normal driving habits.

    And this is where all the problems begin, because if you were to believe leptin researchers and proponents of the leptin insensitivity theory, then you would not predict that normal driving behaviour would resume. Rather, you would predict that the more fuel there was in your fuel tank, the more profligate you would be in its use. That is, putting it in conventional metabolic terms, as leptin levels increase, metabolic rate should increase, and appetite should decrease. If this does not occur, conventional leptin wisdom has it that what is being observed is leptin insensitivity. But if we were to put this back into automotive fuel gauge analogue terms, it becomes a ludicrous proposition. Except in rare marginal cases, nobody sets out to purposely waste gas from a full tank. Instead, normal people without personality disorders stop thinking about it, and commence going about their regular business because they are concerned with having a qualitative amount of gas in their tank, they merely want "enough". The idiot light in the dashboard is a last ditch effort short of your engine dying to draw your attention to the fact that you definitely do not have enough fuel.

    The Metabolic Idiot Light

    So what if leptin is the body's equivalent of the idiot light? If this were the case, then we would definitely expect to see an asymmetric response to leptin levels, with low leptin levels eliciting much stronger responses than high levels. If you were on the verge of starvation with death imminent, drastic measures would be called for. Conversely, if you're sporting a nice fat pad around your midriff, there is really no cause for metabolic concern.

    We see this play out with the seminal research on Ob/Ob mice that produce malformed leptin incapable of binding and activating the hypothalamic receptor. These mice are in constant panic mode, exhibiting voracious appetites despite extreme adiposity - the idiot light does not turn off regardless of how much they eat. Infusing normal leptin into their system turns the idiot light off, the fuel gauge registers a full tank, and they resume driving as normal, eating less and increasing their metabolic rate - reverting to normal. Note that this interpretation of low leptin as the metabolic idiot light fits the observed data, and, moreover, does not suffer from the problem of leptin insensitivity because what is of concern is low leptin, not having "enough".

    What Does This All Mean

    Practically speaking, if this framing of leptin as idiot light is accurate, then there can be no such thing as a leptin reset diet intended to increase leptin sensitivity, because your body is already quite sensitive to leptin levels, it's just that it only cares about low levels. You may, however, find that leptin starts to play a role when you successfully lose weight, to the extent that you come close to the threshold of what in your metabolic context constitutes "low" leptin levels, at which point, your appetite will kick in, and your metabolic rate would drop. However, this would happen irrespective of the particular details of your diet, whether you're on a juice fast or overdosing on protein, it doesn't matter. Once you cross the low leptin threshold for you, appetite and metabolic rate will be affected.

    There is a certain liberation that comes from seeing things in this light, because it frees you from obsessing about controlling your leptin levels, and focuses your attention back on your diet. Which then brings us full circle to the question of what should you eat? Paleo / primal is probably not a bad place to start.

    Last edited by pklopp; 03-27-2012, 05:40 PM.
    My blog :

    Interested in Intermittent Fasting? This might help: part 1, part 2, part 3.

  • #2
    Thank you for dropping some much-needed Real Talk on this subject.
    “The whole concept of a macronutrient, like that of a calorie, is determining our language game in such a way that the conversation is not making sense." - Dr. Kurt Harris


    • #3
      I look forward to the rest of this series.
      Lifting Journal


      • #4
        Welcome back

        Very clear analogy, and I'm very much looking forward to the next instalments!
        Started Feb 18 2011

        Tried basic primal and almost everything else in pursuit of IBS control, mood stability, and weight loss.

        Journalling here


        • #5
          oh my god thank you. the insanity on these forums (fiercehunter and others), is just that - insane.


          • #6
            Thank you. There's interesting stuff out there relating to leptin and obesity (the study on Ramadan fasting and leptin is interesting), but the whole leptin reset thing is completely over the top and way outside anything to do with the actual science.
            “If I didn't define myself for myself, I would be crunched into other people's fantasies for me and eaten alive.” --Audre Lorde

            Owly's Journal


            • #7
              Thanks a lot for this. I was new to the forum and was wondering why replies are consistently off topic with certain members.

              It comes to a certain point where reading food and diet is just not that appealing to me, and this leptin reset stuff treads into that territory. This is coming from a guy who reads Mark's articles, and those on other health sites quite consistently!


              • #8
                Good read, though I've honestly never read the Leptin reset thread thingy. I have read a book about controlling your leptin and the recommendations just seemed like common sense rules for eating -- train your body to expect meals at certain times instead of grazing all day long to avoid overeating, and if you're not hungry, don't eat. I walked away from it feeling kind of, "Well, duh!" So, I never bothered with the thread here. I look forward to your next installment!
                Motherhood: When changing from pj pants to yoga pants qualifies as 'getting dressed'.


                • #9
                  I've done plenty of study on various interactions of neurotransmitters and hormones. All I know for certain is that the concept of a "master" hormone is our own manifestation of control that we as a race so often can't help but grasp at. It was the thyroid, no insulin, no leptin......on and on. In my estimation the interplay of hormones is so far beyond our grasp at this current juncture that this is the actual reason paleo makes the only sense as for how to eat and live.


                  • #10
                    I don't really understand this whole leptin thing, but the thing is, I don't think anyone really understands most of what happens in the body or why, and honestly I don't think we really need to. We just need to eat real food. Not too much. And not constantly, all day and all night long. Our bodies will deal with the task of understanding leptin so we can focus on other stuff.

                    I haven't gotten everything figured out. I'm a work in progress. I like to experiment. I'm discovering how my body thrives. So far, I know that it really likes intermittent fasting.

                    Do I get hungry more than I wish? Sure. I'm a 5'4 lady who just ate 2,400 calories today, and guess what? Just thinking about food and leptin and hunger is making my stomach growl. But I know that I ate enough good healthy food that contained about 1,000 the RDA for everything, I fasted yesterday, and I plan to fast tomorrow. So, in the next 2 minutes I'll talk myself out of being hungry, and I'll be fine. There's no leptin magic there - just a person taking control. In the end, all we can do is take control, make some good choices, and decide when to listen to the hunger and when it's behaving like a tantruming child that needs to be ignored for the greater good.


                    • #11
                      Originally posted by Jac View Post
                      Welcome back

                      Very clear analogy, and I'm very much looking forward to the next instalments!
                      Thank you ... Sorry about dropping off the face of the earth, but I started reading that monster leptin thread about a year ago and it took until now to finish it ...

                      My blog :

                      Interested in Intermittent Fasting? This might help: part 1, part 2, part 3.


                      • #12
                        Great Bro-Science, but I would suggest going to Google Scholar, type in some keywords like, Leptin, Obesity, Leptin-resistance, etc... Then sort the hits to 2011 and newer, uncheck the 'patents' button and see what you get, then read some of the studies. You will see things related to Leptin resistance as the real problem. Leptin doesn't matter, it's the leptin receptors that matter. Just like in diabetes, insulin isn't the problem--just the result, it's the insulin receptors that are out of whack. I just pulled this from Google Scholar for instance.

                        The hormone leptin, secreted predominantly from adipose tissue, plays a crucial role in the regulation of numerous neuroendocrine functions, from energy homeostasis to reproduction. Genetic deficiency as a consequence of leptin or leptin receptor mutations, although rare in humans, leads to early onset of chronic hyperphagia and massive obesity. In most human obesity, however, leptin levels are chronically elevated. Under these conditions of persistent hyperleptinaemia, leptin resistance develops, and signalling through the leptin receptor is curtailed, fuelling further weight gain. Here, we review the role of leptin receptors in the regulation of feeding and obesity development. Leptin receptors are found in each of the major components of the CNS “feeding” circuitry—the brainstem, hypothalamus and distributed reward centres. Through these receptors, leptin exerts influences on signalling and integration within these circuits to alter feeding behaviours. Although some progress is now being made with peptide analogues, the leptin receptor has not proved to be amenable to small molecule pharmacological intervention to date. Where clinical benefit from recombinant leptin administration has been achieved, this has been under circumstances of complete endogenous leptin deficiency or relative hypoleptinaemia such as in lipodystrophy.
                        Keywords Leptin – Leptin receptors – Obesity


                        • #13
                          thank you. Day two of my leptin reset and I am walking away. I'm sorry, I just don't think 6 slices of bacon, 4 eggs, and lots of butter is healthy unless you spend 5 hours at the gym.
                          SW175ish GW140 CW157

                          height 5'6"

                          Official for real start date 1/10/12


                          • #14
                            Originally posted by Drea6681 View Post
                            thank you. Day two of my leptin reset and I am walking away. I'm sorry, I just don't think 6 slices of bacon, 4 eggs, and lots of butter is healthy unless you spend 5 hours at the gym.
                            I dont see a problem with bacon/eggs/nor butter. I dont see why this would equate to 5 hours in the gym either. Fat on its own does not make you fat. I have had that for breakfast many times.

                            I just think there is no way that we would know the exact diet that would increase leptin receptors.. Is it worthy of an experiment if you are stuck? Sure thing.. as long as you feel good doing it. However, it certainly doesnt make Dr. Kruse an all knowledgeable being.. I heard him on the Paleo Summit and was like WTF what planet do you live on?
                            Primal since March 2011

                            Female/29 years old/5' 1"/130ish lbs


                            • #15
                              Originally posted by Neckhammer View Post
                              In my estimation the interplay of hormones is so far beyond our grasp at this current juncture that this is the actual reason paleo makes the only sense as for how to eat and live.
                              Exactly, for me paleo is the ultimate "keep it simple, stupid" philosophy of diet.