Intermittent Fasting and Leptin

Print pagePDF pageEmail page

Readers Summary

  1. How does Intermittent Fasting (IF) work biochemically?
  2. Who has great protocol on IFing?
  3. What is the AMPk pathway and how does it affect IF?
  4. What happens in the brain, liver, and muscles when you IF?
  5. Why does IFing not work when someone is leptin resistant?

Today, I decided to blog about Intermittent fasting (IF). Since I wrote the Leptin FAQs, I have been bombarded with requests about IFing and how it relates to leptin signaling. I mentioned in the FAQs that I love IFing, but not when someone is LR. The reason for this is how the AMP-activated protein kinase pathway (AMPk) works. THe AMPk pathway is best described as a fuel sensor for lipid and glucose metabolism. In humans, the control of glucose homeostasis is governed by the balance between intestinal absorption and endogenous hepatic production by the liver and the uptake done in the muscles. Intermittent fasting is a behavioral modification that specifically alters feeding behavior to cause disruptions in glucose and lipid metabolism in humans. It also has specific times when exercising is done as well. When it is practiced well is can lead humans to shred body fat and really control their ability to generate muscle with workouts and re-feeds. I would strongly recommend that you take a look at the leangains protocol sometime on Martin Berkhan’s site. The key question many have asked me is how does it work and why can’t I do it right off the bat regardless of my leptin status. This is a loaded question with an answer that may make your head hurt but you will understand why IFing won’t work if you are leptin resistant (LR).

The reason why it is counter productive in LR is the AMPk pathways requires really optimal leptin sensitivity and signaling to be occurring between the brain, liver, and muscles. At its core, when one IF’s it creates a “temporary” cellular stress due to lack of food at certain times. The reason for this is tied to the microbiome’s ability to stimulate molecular hydrogen release from the microbiome.  IFing’s main benefit is in creating a diverse microbiome in the gut.  Molecular hydrogen is another sophisticated way to repair an altered microbiome besides IF.  AMPk is specifically upregulated in times of cellular stress. Some examples, are nutrient deprivation, ischemia, hypoxia, exercise, glycogen depletion and oxidative stress. When one fasts, this also counts as a cellular stressor.

Exercise or fasting increase glycogen depletion in the liver, which in turn increases whole body fat oxidation.   Fasting always increases autophagy but exercise has the capability to both increase it or turn it off.  This is why exercise comes with caveats.  It turns out when someone is LR or their circadian signals are exercise is detrimental.  Few ‘crossfitters’ or endurance athletes know this.

AMPk is activated by exercise and muscular contraction because both deplete energy stores from ATP to AMP.   The key signal is glucagon for turning autophagy .  It turns out glucagon is a hormone that enhances macro-autophagy. When the redox potential is high it has a stimulatory effect of glucagon and on autophagy.  Here is the caveat:  It has no longer been observed in old animals.  Moreover, it is also absent in endurance athletes and it is one of the reasons so many marathoner’s die of acute heart disease at races.   WHY?  A low redox state is present.  With aging we lose 9% of our redox potential per decade.  Autophagy is evolutionarily conserved stress response that is present in all living cells. Like apoptosis, autophagy is a programmed response and has several sub-pathways.  Unlike apoptosis, autophagy promotes life rather than death.  Apoptosis is a suicide program for cells.  Autophagy is the best way to get rid of bad mitochondria without killing the cell.

Exercise also increases AMPk in the liver and at adipocytes simultaneously.  The amount determines the back ground redox state.

AMPk is also controlled by leptin and adiponectin. Both hormones are released from adipocytes in response to nutrient excess and both activate AMPk in peripheral tissues. Leptin however, also appears to decrease AMPk levels in the brain while ghrelin (stomach incretin released in fasting causing hunger) increases levels of AMPk in the brain. Ghrelin is also a potent stimulant to growth hormone release and builds leans muscle mass. AMPk activation also inhibits glycogen storage and increases glucose re-uptake, it appears to be very involved in improving insulin sensitivity.

When AMPk is activated in the brain it down regulates protein synthesis in the body. So the brain effect is quite different then the peripheral effects at the liver or the muscles. Therefore we cannot make muscle when AMPk is upregulated in the brain. Protein and glucose nutrients both decrease AMPK pathways and simultaneously increase mTOR activity in the hypothalamus. A higher mTOR signal in the hypothalamus decreases our appetite and food intake and this inhibits our ability to make muscle. It does this by decreasing neuropeptide Y (NPY). This also explains why the leptin Rx calls for a very high protein and low carbohydrate intake at breakfast. A high protein breakfast (think Leptin Rx) leads to decreased food intake and eventually a decreased body weight. This is precisely what humans experience in a leptin reset. It essentially becomes a very natural way to IF without trying to.

Normally in the brain, leptin increases hypothalamic mTOR activity and decreases appetite and food intake. The inhibition of mTOR signaling diminishes leptin’s anorectic effect and we increases food intake. Thus, mTOR also acts a cellular fuel sensor (opposite effect of AMPk) whose hypothalamic activity is directly tied to the regulation of energy intake. Consistent with this cross-regulation between AMPK and mTOR to control food intake, research also now shows that the activation of these pathways occurs in the same specific neuronal subtypes of the hypocretin neurons that leptin controls. In essence, this means that for this system to work well in IFing you must have good leptin functioning in the brain to get the maximum effect.

I can hear you asking yourself now, how does AMPK lean you out if your brain won’t allow you to make muscle? AMPk allows us to become very sensitive to insulin peripherally at the muscle and fat cell levels. This is why many researchers are now looking at the AMPk pathway for T2D and for Alzheimers. AMPK switches off all anabolic pathways such as fatty acid synthesis, triglyceride synthesis, and cholesterol synthesis as well as protein synthesis and transcription that consume ATP, and switches on catabolic pathways that generate ATP, such as fatty acid oxidation and glycolysis. If you are dehydrated you can not take maximum advantage of this.

That means that AMPk stops us from making all fat, stops the liver from making fats from protein and carbs that need storage, while simultaneously making us burn fat and sugar to replete our energy stores (ATP).  So if a human is LS and uses intermittent fasting you can stimulate muscle building with re-feeds. How, you ask?  When a human re-feeds they are dramatically increasing mTOR and decreasing AMPk at this time. The re-feeds also are dramatically increasing leptin too.  If you are already leptin resistant your brain will never see this signal. This is why IFing is worthless in LR states.  Re-feeding immediately turns on muscle rebuilding.

Martin’s Leangains protocol seems to take advantage of this by favoring muscle growth while trying to limit the creation of fat peripherally. Since re-feeds raise leptin quickly, the person is activating AMPk in skeletal muscle (explaining why people often lean out after a re-feed) and inhibiting it in the brain. This helps explains why people will also lean out after a re-feed as well provided they are leptin sensitive and have a good redox potential.

Leave a Comment

Your Shopping List for this Post

Additional Resources




  1. @ Tony I did not publish your comment because I felt it may confuse some but here is the answer I think you were looking for. Some supplements have the theoretical capacity to directly or indirectly activate AMPK including metformin, thiazolidinediones, adiponectin, leptin, ciliary neurotrophic factor, interleukin-6, alpha-lipoic acid, resveratrol, epigallocatechin-3-gallate (a main catechin of green tea), cannabinoids, ghrelin and certain plant polyphenols. I have used resveratrol, Alpha lipoic acid (ALA), and ECCG (green tea) for AMPK modualtion in the past. I would not recommend using thiazolidinediones ever for this because the manner in which it works on AMPK is to increase the sheer number of fat cells which I think has many downsides. Here is a reference to peruse.

  2. So the solution for us chubby folks is what? Don't IF? Or more refeeds? Shorter fasting? Breakfast? I'm confused..

    • @ Axel You should not be confused. Its crystal clear. If you are LR you don't IF. If you are not sure if youre LR get tested. If your fat and you are not progressing you likely have issues to deal with. The Leptin Rx, FAQ's and the IF posts are always here to be a guidepost. I can not make it any clearer than that.

  3. You were right, that hurt my brain. I'll re-read it and hopefully digest it better.

    I keep hearing that I should eat protein first thing in the morning, but I'm never hungry until afternoon. I've tried to force myself to eat breakfast, but I always do it for a day or two then forget. It's easy to forget to eat when you're not hungry. 🙂 In fact I tried last week and it lasted one day.

    I generally eat twice per day. Once in the early afternoon and again in the evening. Do you think I should continue to try to eat in the AM?

    Love your site, by the way. I followed a link here last week and I've been doing a lot of catching up.



  4. Thank you for posting this. I'm one of those who tried LeanGains for a few months with mostly poor results because of still being LR. I think it also compounded my Adrenal Fatigue issues. I lost a bit of weight and added some strength, but I never "felt good" in terms of consistent energy levels and lack of hunger.

    I'll be looking into it again though once the adrenal function is better and I'm sure I'm leptin sensitive…maybe it'll be part of my 2012 work…

    I sure do miss the cheesecake aspect right now 😉

    Side note — curious if you've ever stumbled on the "Lean Saloon"? Johnny is a really nice guy and seems to do good work…it would be good to see him integrate your findings on Leptin though. His work seems well suited to pick up where yours leaves off…HIIT, IF, and integrating Paleo/Primal into a lifelong health strategy once the hormones are fixed. He's slowed down considerably as he prepares to become a father, but the blog is a nice repository of IF info.

  5. @Jim are you over or underweight? Is your energy levels OK? Do you have cravings? If you don't have any of these things you likely are not LR and don't need the Leptin Rx or have to worry about breakfast. But I would tell you this. If you do have sleep or energy issues I would bet testing would be an eye opener to you.

  6. @livinlite I did not know about Johnny or his blog. Thanks for pointing it out. I went over there to say hi and post my information for him to peruse. Thanks.

  7. Great post. I've been naturally doing IFing after becoming LS, as I rarely felt hungry for dinner. So I did eat in an 8-hour window. My question is: how often pr week can you IF if you have reached LS and have no issues with energy? I've been doing it about 2-3 times weekly. Also, I came across organic reservatol online as capsules. Would you recommend taking these as a means of burning fat? I don't drink enough Pinot noir to get enough through my wine.

  8. @Glamorama You can IF as much as like as long as your energy sleep and craving remain at bay.

  9. Can you clarify, so if I'm LS and still following a Paleo Diet, I will have difficulty gaining muscle without the excess carb refeeds?

  10. Hi Dr. Kruse~

    I'm sorry to ask yet another question, but I have looked extensively through the comments and haven't found anyone with my situation….I am a 31 year old woman, very fit by most standards…I am a personal trainer, and I work out every day. After reading through everything, I am wondering if I might be LR…I have serious carbohydrate cravings, have been battling an ED for several years, have been diagnosed with sleep apnea, (am on a CPAP now), and have a very large appetite. I am able to control my weight (but would LOVE to get rid of about 10 lbs) through extremely clean eating, Paleo style as of late, but still with the pretty intense cravings, especially after dinner. I have had a bingeing issue, which I would eat large amounts of carbs, but have been able to control it (mostly) by eating Paleo, but still have small binges of fruit, nuts, or the like. So, my qestions are: could I possibly be LR? If I try your RX, can I still exercise? (no chronic cardio….i don't like that either)Any other recommendations? I think that's it….Thanks in advance. I would love to get rid of these issues once and for all….they have been plaguing me for years!

    • @Susannah You probably do have LR for sure. My bet your issue is multifactorial. I have not hit on ED but they usually all originate in the brain and involve bad signaling between the hypothalamus and the incretin system of the gut. Your symptoms strongly suggest it. To tell you exactly what to do is impossible without labs but I would warn you that cortisol from too much work will kill you. And the fact that you are eating that many carbs and are still craving tells me your NPY is running wild in your brain. You may need to go with a different macro profile to reign in NPY, NYY, and gherlin……for sure.

  11. Jack, Love your blog. I would love a daily meal plan while doing LR. Particularly lunch and dinner. I have breakfast down, but having trouble with the other two meals.

    Thank you.

    • @Joe I doubt you will ever get this from me. Its just not my angle. There are so many great paleo sites for meals. Diane Sanfillipo for example or Whole9. Me…..I'm just a clinician trying to open the hood of your ferrari and get you to understand how all the shit underneath works. Maybe if I write a book someday about this I will add this……but I just cant see it. I do post pics of what I eat on FB a ton. But I cook by intuition of what my body needs. It is a bit easier for me to "feel" it because I test myself often.

  12. In your response #6, what specific tests would you do if sleep only is an issue? At 5'6" male, age60 and weight of 142 with zero carb cravings, no matter how many hrs of sleep i get, falling asleep is tough. Not tired though. I will find it worsened if i eat a light dinner, but that may be the result of light brkfst and lunch. In last couple of days i have started on BAS for me, and no change yet. Maybe some specific test recommendations from you would be great. Thanks

    • Hypothetically speaking someone might consider a salivary cortisol assay, DHEA-s, and Free and total Testosterone for a good sleep assessment.

  13. so….any idea where i would find that information? it sounds like i am a MESS!

    • @Susannah you just need to sit down with a good doc and get it ironed out. You also might have to do some things that sound counter intuitive to you but you will get better.

  14. Jack, thanks for the reply.

    On April 15th 2009 I weighed 420 pounds and I'm currently about 265. Most of the weight loss was from unrestricted low carb paleo style eating.

    Most of the weight loss came very quickly and easily, but over the last nine months or so my rate of loss has gone from 5-10 pounds per month to long plateaus where I bounce around in a 5-10 pound range. For example I hit 270 in April, I believe, and then spent the last few months bouncing between 270 and 280. Over the last couple of weeks I've finally starting losing weight again by upping my activity more and counting calories, which I hadn't done since the very early days of switching to paleo.

    My sleep is good, energy is great. I lift weights 2 or 3 times a week and do interval sprints once or twice a week.

    I guess my real question is what is the effect of having a lot of fairly empty fat cells. I know leptin is released by full adipocytes, so is having many not full fat cells hurting my weight loss? I've got a lot of flappy skin with deflated fat cells. I've considered getting plastic surgery to tighten that up.

    I plan on getting some of the tests you've mentioned done next time I go to the doctor, but it will probably be a while. Last time I was there he said I was so healthy he didn't need to see me for 12 months unless I had some reason to come earlier. 🙂 When I first started seeing him at nearly 400 pounds I was on blood pressure and allergy meds and anti-depressants and he wanted to put me on statins. Now I'm on zero pills other than some vitamin and mineral supplements.

    I love your site. You seem to be much more on the cutting edge of the neuroscience than anyone else in the paleosphere. Wow, this got kind of long and rambly. 🙂

  15. Jack, thanks for you comments and I completely understand. I guess my real question is I have a lot of weight to lose (175 lbs) and am wondering about the number of calories to eat each day. Obviously the less you eat the more you lose, but is their a number of cals that is to low? Thanks for your help.

  16. @Joe

    For me, when I switched to eating real, whole foods with a low carb emphasis, I didn't really need to worry about calories. I counted them in the beginning out of curiosity, but only for a couple of weeks. What I did track was the number of grams of carbs, keeping that under 50. I lost over 100 pounds doing that and eating to satiety on a diet of steak, eggs and green vegetables (broccoli, brussels sprouts, spinach, etc).

  17. Hey Doc, I hear people of Metabolic Typing and Paleo Diet say that if your nutrition is in balance, you suffer less from social anxiety and have better mood. Why would nutrition affect your social ease in interacting with others? I feel somewhat more positive in my daily life after following the Paleo Diet but i cannot tell 100% if its a placebo effect.

    • @Dan H. Your brain is what your body consumes. All your neurochemistry and wiring depends upon how you take care of it. If you eat well you feel well if you dont you get put on drugs that still dont work because the underlying abnormality is not corrected.

  18. Susannah, my daughter is 13 yo and is very active, eats paleo, but binges on fruit. when she stopped the fruit, she could control her cravings.

  19. Hey, Jack – I have been having really good results by IF'ing daily from 6pm til 11am. I work from 7-4:30, so this fits perfectly into my normal day. I wake up not hungry and don't start getting hungry til about 11am. I eat a huge paleo lunch and a smaller paleo suppper w/2-3TBS of CO as dessert. No snacking outside meals. My labs and my life all point to LR. I'm the guy on PH who quit his Synthroid btw. Thanks for all your work here and at other places in getting your info out to the world.

  20. They Doc, Thanks again for another great entry. I have a few questions. First what do you think is the minimum amount of protein we need? Do you think the .7-1.0 G per pound lbm is reasonable? The other thing thing I was wondering is do you see any problem with once a person in LS again and loosing weight getting most of there calories from lean meats to maximize on the thermal and satiety effects?

  21. Hello Jack! You are saying that refeeds are activating AMPk in skeletal muscle and that people lean out because of that. But don't you have to take account with the surplus? If my maintenance is 3000kcal and I refeed with 3200kcal, some of those calories will be stored as fat and used for building muscle right?

    Or are you saying that the surplus will be burned off due the AMPk? What about protein synthesis? Your body can't build muscle and lose fat at the same time right? I hope you can clear this up for me.

  22. Wow that's crazy. And I read also that our hormone levels like testosterone, cortisol, oxytocin etc. can influence behavior, at least for men (i.e. you act differently if these levels are appropriate). I understand how to lower cortisol, is there a good way to naturally raise testosterone? Do you recommend taking DHEA for individuals recovering from LR and lower levels of testosterone?

  23. To be specific, I read in an article (I think psychology literature) that it is testosterone will helps us be more swift decision makers, but high cortisol levels drop our competitive levels. i.e. highly stressed individuals back out of a competitive game. If this is true, and we increase testosterone/decrease cortisol nutritionally, it will surely improve men's health from a mental/social point of view as well as a physical one. Thanks and keep up the hard work, Dr. Kruse.

  24. @Tim. As long as you suffer no cravings or sleep problems go for it your IFing plan

  25. @CM etc…..I think protein recs have to be made I. Context of seeing someone and looking at their serial labs. I think 0.7 to 1.2 is real safe for most people but for me personally this would not work based upon my own labs. It must be done in the patients context.

  26. @Dan H. This absolutely brings home the point I made to you above. The brains outflow is the hormone response. that response is derived from what we eat, how we eat it, and the timing of when we eat it. We all partition calories based upon the epigenetic switches settings in our hypothalamus. Can we alter those switches? My belief is we can with sustained feeding alterations. That is the basis on paleo 3.0 for me. Some other physicians like Dr Harris take an easier approach and just avoid the bad stuff to get a good result. I think his way has merits. It lowers your cortisol because food choices should not be stressful but for some they are. I think avoiding Neolithic foods is good…….just not optimal. And for me if a patient wants good they easily can get good without me. If they want optimal……it takes more tinkering with biology to get them there.

  27. @Susanna where you would find that info is to find a psychiatrist who specializes in ED and evolutionary medicine. I would consider asking Emily Deans over at her blog for a recommendation. I am currently working with a psychiatrist who wants to add evolutionary medicine to his ED practice but he is not up to speed as yet. When a doc becomes interested in this brand of medicine we really need to support their decision and help any way we can.

  28. I've been looking into the leangrains and considering its protocol and how to do it based on what I've learned from the Leptin Rx. Some of the ideas though directly oppose the Leptin Rx. like the number of hours in between meals, eating very late/near bed time, and skipping breakfast. So if I was to try this, I was thinking I'd just eat breakfast and then a late lunch to get the 16 hour fast with a workout in between. Any thoughts?

  29. @LSS. This is why you do it after you're LS!

  30. I realize that! Considering comments you've made about breakfast and not snacking ever, they seemed to be hard and fast rules with you, even Post Rx. It didn't seem congruent even if your LS, that's why I asked.

    • They are……but IFing does help some after your reset. When someone is reset they often can go with one to two meals when they are eating a BAB. I think everyone who has prorperly done the reset is pretty shocked at how the BAB changes the game so to speak. It destroys cravings and hunger pretty quick. Most people think they cant eat a BAB and then in a few weeks they are like why have I not done this sooner?

  31. what about skipping dinner during the leptin reset?

    I eat my nice BAB, go to work, then eat a nice primal low-carb lunch at noon. after work I usually want a snack, but I've been fending it off with water (sometimes with a scoop of glutamine powder) and then often finding myself not hungry at 6. you said in the FAQ that if we can't eat by 7, we should just drink water and go to bed early. I've been doing this on a pretty regular basis (plus taking my fish oil and medications just before bed), is that ok? should I force myself to eat SOMETHING or just let it go?

  32. Dr K.

    Thank you for putting all this info out and have nothing to sell anyone. It is clear where your heart and motives are. You are quite literally saving lives and changing the world.

    I ate a paleo diet for 2 years and lost 100lbs and reversed my diabetes. Interesting things that happened were: I started to be drawn to exercise at very high intensities for short periods and not feeling hungry until dinner time.

    So for over a year, I have been eating 1 meal a day (dinner) simply following my body's hunger cues. Sometimes if I have to eat lunch for social reasons, I simply have no room for dinner. Food choices are always low carb paleo.

    Exercise includes 4 times a week of heavy lifting and 2 times a week of max sprints (my heart rate is always hits >95%). I'm in south east Asia and it's summer all year long and I make sure I take a 1/2 hour walk with as little clothing as possible at noon every single day.

    I just had my body fat measured at 8% using calipers and have a waist line of 29" at 5ft 8" (yes I have a 6-pack now). Coming from a body fat of 38% with a waist line of 42", I'm over the moon.

    What to me is mind boggling: I stay lean despite eating as much as I want, whenever I want (which is naturally once a day), have no struggle with any sort of cravings for non whole foods, spend very little time exercising, have better sleep than ever, do not remember the last time I have gotten the flu, astounded my dentist as she claims that my decayed molar has somehow magically healed itself over the course of a year, have a HDL of 90 and trigs at 30, my 25 hydroxy D level is at 75 without any supplementation…etc.

    I just feel freaking great. Friends say I look like one of their atheletic college students now despite being in my 40's. I even lost my man boobs that have been one of the major sources of insecurity in my life. This is huge cos I had them since I was 5.

    I just want to thank you for explaining to me why with all your writings. I finally have an idea. Although I never followed your protocols to begin with (you weren't blogging then), I did them all correctly and am experiencing the best health of my life.

    For people who are wondering, try Dr K's advice and just watch yourself change. And do it right without half-assing.

    • @Adam…….awesome for you. And I am so glad you posted this here. I may repost this in the Leptin Rx blog because I think it will be seen by more folks. Many dont believe optimal can come from doing the small little things right daily. You my friend are that billboard.

  33. Is there a way to summarise it, otherwise I can't make sense of it, e.g.


    mtor in the brain – up

    mtor in muscle – down

    ampk in the brain – up

    ampk in muscle – up


    mtor in the brain – up

    mtor in muscle – up

    ampk in the brain – down

    ampk in muscle – up


  34. Dr. Kruse,

    Can you clarify how you look at the reverse T3 test as a biomarker for LR?

    Is it that 90% of LR patients have elevated RT3, so odds are in one's favor against LR if RT3 is within the middle of the range of the assay (say 200 with a range of 100-350)?

    If a person is not overweight and <15% bodyfat, but has somewhat elevated TSH and lowish T4/T3 and low sex hormones (and all the associated symptoms), where does this person fall on the LR curve? Does the LR-thyroid interaction always manifest itself as elevated RT3, or could it simply mean that T4/T3 are lower despite proper signals from the pituitary?

  35. Hi,

    I have various issues due to Lyme disease and babesia, but I would like to figure out if LR is part of my issues. I have been IFing (eating lunch and dinner only) for a while now and I eat a low-carb, moderate protein, high fat diet. Still, it is hard for me to keep my weight down. I realize with Lyme there are a multitude of issues such as insulin resistance for one, so like I said, I would like to figure out if LR is one of them.

    Finally my question, is a fasting leptin blood test sufficient to determine if I am LR? My thyroid is being monitored and my RT3 is low and good in relation to FT3. What else should I get tested? I believe I had a low fasting leptin level at one point. What does that indicate?

    On a different note, are you only seeing patients for neurosurgery? Nashville needs a good Paleo friendly doctor. I am so tired of doctors telling me to eat grains and reduce fat.

    Thanks for all the articles.


    • @Kristina It sounds like LR is not your problem. Lyme Dz and babesiosis maybe. The real issue behind these tick borne diseases I think is failure of the immune system to work well and this causes it to become hyperactive over time. Chronicity of infection is a problem. Much in vitro evidence now exists to demonstrate that Borrelia borgdorfeii (Bb) can lodge intracellularly in human endothelial cells, astrocytes, fibroblasts, and macrophages. Bb in vitro has been shown to enter B Lymphocytes and to exit drawing with it the outer surface membrane of the lymphocyte. Bb in vitro can modify its shape into potentially cyst-like forms; these forms however at present are of uncertain significance. These findings suggest that failure to eradicate Bb completely by antibiotic therapy may be due to intracellular localization in vivo, the selection of resistant strains, or sequestration in sites (such as the central nervous system) where antibiotic penetration may be less adequate. If it is a totally intracellular pathogen it stays away from antibiotics and wrecks intracellular signaling to cause its symptoms. Lyme patients globally look like a car in need of a major tune up. They are energy inefficient. This is the source of the real problem. The LR can make you more efficient. I am not sure how it affects an intracellular pathogen.

      The post-infectious inflammatory hypothesis also is supported by several lines of evidence. For example, patients with Lyme arthritis who carry the HLA-DR4 or DR2 allele are more vulnerable to developing a chronic antibiotic-resistant arthritis. Indirect evidence exists to support molecular mimicry as at least one possible explanation for persistent symptoms.

  36. Dr. Kruse,

    Thank you for that reply. I really appreciate it. I am hoping to avoid antibiotics actually but I have been trying to build my immune system via diet, removing toxins, fermented foods, etc. yet I am still not well. I went from eating Paleo, exercising 5 to 6 days a week, and being in great shape (physically and mentally) to doing hardly anything and having a hard time doing my job due to brain fog.

    Assuming you don't treat Lyme patients (unless you do??), can you recommend any physicians in Nashville that might be able to help?

    I heard Dr. Bernui is pretty good but know nothing about him or his views on diet.

    Thanks again,


    • @Kristina…….pickings are slim here. Bernui is not a paleo guy. I hear from many he is a veggie. I am not sure because I have not spoken to him in years.

  37. Well, that is disappointing but I guess I don't have to follow his dietary advice or guidelines. I am really not sure who else to see besides Dr. Klinghardt in Seattle.

    Thank you for the replies. I appreciate it.

  38. @Kristina……..true. Going to him certainly wont hurt you to evaluate him.

  39. Great analysis of Martin Berkhan's Lean Gains protocol. His site is very popular among younger gym goers. But a big part of his IF plan is skipping breakfast and eating within an 8hr window from lunch to dinner. Do you have any negative thoughts on that as you prescribe a big breakfast?

    He also believes in high carb refeeds for temporarily boosting leptin on a diet and increasing satiety. Seems like a neat idea but does this only work for LS? I assume from reading Mastering Leptin and your blogs that this would only exaccerbate someone who's LR.

  40. Hi Dr. Kruse,

    What is your thought on a water fast or broth/tea fast? Supposedly fasting heals the body but will this have a negative effect on leptin resistance?

    Thank you,


    • @Kristina……it would make Leptin resistance worse. Leptin responds aggressively to calorie restriction and this is why IFing is an epic fail for those who are LR.

  41. OK so I'm LS for a year now, and I need an instruction guide to IF. Just drink water from 6pm to 11am (or longer?), followed by a BAB? How many times per week? What are your specific guidelines as to how to do this? I especially need to try this since I can't do Crossfit for another 10 weeks. 🙁

    • @Jodi I would say head over to to check his protocol out. I'm not ready to go to my IFing protocol just yet.

  42. I did. Just wondering if you think it would be OK to do it w/o weightlifting, or wait until I have the green light to workout first. Doc says no weights or Crossfit until 11-12 weeks post-op. So far this has been the longest 3 weeks of my life. Can't imagine what my muscles will feel like in 9 more weeks. UGH!

    • @Jodi exercising right now might not be smart since you're healing. I would go ketogenic paleo and improve your sleep while your healing over exercise. When you are off crutches and sleeping 8 hrs a night then I would go back to exercising.

  43. How do I go from Paleo to ketogenic paleo? Just cut out ALL carbs including veggies?

    • @Jodi its simple…….lots of fish, seafood, and offal/grass fed meat in coconut oil or ghee…….as staples. You live in New Orleans so for you this is a lay up. Next time Im in town I expect you to take me to Drago's for a few dozen BBQ oysters. I can taste them right now!

  44. You got it, doc! But I think you meant chargrilled… BBQ isn't paleo. 🙂

  45. On leangains site, Martin believes in high carb refeeds for temporarily boosting leptin on a diet and increasing satiety. Does this work and ok for LS person?  So a day of refeed being Paleo carbs of fruit, potatoes/ sweet potatoes etc., high protein and low fat (50 grams or less).   (is white rice ok?).  So non lifting days lower carbs and on lifting days low fat high carbs and high protein. 
    Should carbs still be tailored for the winter months?
    Martin also recommends skipping  breakfast and working out fasted. Whats your thoughts on eating breakfast and skipping dinner or lunch and dinner for the fast?  Workout may or may not be fasted. Also the refeed would begin in the morning with breakfast. 

    My main concern is the high carb refeeds. Are they needed and healthy?  Can refeeds once LS be done with a higher fat intake instead of carbs or does this negate the effect?

    Once again thanks so much for all your insights and posts. It has dramatically changed my perception of health. 

    – Dan

    • @Dan once you are LS you can skip breakfast and go to eating one meal a day… to your question are the needed or healthy no one knows this definitively as yet. Mike Eades has a comment in his book/blog that anything over 5 gms of carbs actually cause damaging glycation. I know of no telomere studies in IF protocols.

  46. Great answer. I love the way you are direct honest and straight up.
    – Dan

    • @Dan it does none of us any good to BS one another. We are all trying to get better… one has all the answers. We all need to search for them. In our community too many spend time wasting time arguing while we need to be helping modern humans move from mediocre to optimal.

  47. @ Dan: Maybe if you don’t want to eat breakfast, you can still ‘fast’ by using Bulletproof coffee. It is all fats, so is fasting but still get the calories for your body to think it is in a fed state.

    Verify with Dr. K, but I am pretty confident in my statement here.

    I find it beneficial to have Dr. K and Bulletproof. I would love to hear Dr. K’s opinions on some of the technology and sleep hacks that Dave uses. (I don’t need the sleep hacks right now since I can afford to go to bed according to natural circadian cycles, but still curious anyhow).


  48. @Gladina Thanks for you insights. I have been skipping breakfast for years now and have done the LG fasting protocol. Lately for the Leptin RX I have been adding back in breakfast and I must say I feel better during the day. I am not focused on when my meal is coming and I can go all day without eating. It makes a 24 hour fast a breeze as I just skip dinner and when I wake up I’m pretty close to the 24 hour mark and still not hungry. In the future I may skip the next day breakfast and then eat a lunch or late dinner for a longer fast to see how that goes. But yeah adding back in breakfast, keeping it keto or rather low carb has been great. That and not going to bed on a full stomach. When I have my last meal for the day I make sure it is 4-6 hours before bed time. That and I make it a higher protein/ fat meal. With Martin’s LG protocol I was counting calories. With eating breakfast and then doing random fasting I have been able to eliminate counting…. I just do a fast here and there as needed and I stay lean. At some point I may add back in some paleo carbs either in the morning or around workouts. But I will use is sparingly and in small steps with foods in season and which serve me best.
    I’ve learned a lot here….. Also working on my CT and that is making a difference in fat and leptin control. I have a ways to go on that one as I still get cold.

  49. Zack leman says:

    If you are leptin sensitive is it optimal to skip breakfast as a part of intermittent fasting or is it NEVER a wise choice to skip breakfast when IF? You mention never to skip it in your post Leptin protocol, but when some people have asked you have said “go a head.” But I wonder, is it optimal?

    • @Zack it depends upon how LS one is to determine if IFing will get you to optimal. in my opinion IFing is a tool of hormesis.

  50. Interesting study showing that my Quilt ideas may have some steam:


  1. […] INTERMITTENT FASTING and LEPTIN – Jack Kruse. Share this:FacebookTwitterRedditMoreLinkedInDiggStumbleUponTumblrPinterestPrintEmailLike this:LikeBe the first to like this post. […]

  2. […] If you decide to Intermittent Fasting do not skip breakfast ever.  It is the key to circadian congruity and optimal body composition.  […]

Speak Your Mind


Time limit is exhausted. Please reload CAPTCHA.

Please Note: The author of this site is not engaged in rendering professional advice or services to the individual reader. The ideas, procedures, and suggestions contained within this work are not intended as a substitute for consulting with your physician. All matters regarding your health require medical supervision. I shall not be liable or responsible for any loss or damage allegedly arising from any information or suggestions within this blog. You, as a reader of this website, are totally and completely responsible for your own health and healthcare.