Leptin: Chapter One

Leptin: Chapter One

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Readers Summary

  1. Why is leptin the Master Hormone?
  2. What labs tell you about your leptin status
  3. Leptin’s connection to the brain
  4. Leptin’s relationship to organs energy requirements
  5. Obesity is an inflammatory condition caused by leptin dysregulation not insulin

Okay, so you have heard me talk a lot about leptin. Why is it so important? It is a hormone that controls all of energy metabolism in the body. Not only that it controls all the other hormones in the body as well. So if it is not working well you can bet that the rest of your hormones are going to show clinical problems as well. I can’t tell you how many people think they have thyroid issues when all the time they have been leptin resistant. One becomes leptin resistant when the brain no longer recognizes the leptin signal sent from our fat cells. Testing leptin is easy to do but rarely done in medicine today. The easiest way is to look in the mirror. If you’re way too fat or way too thin guess what? You are leptin resistant, most likely. Biochemically we can also assess it with a test called a reverse T3 level. This is rarely ordered because many docs don’t know about the test and because it is not covered by insurance. Reverse T3 is a competitive inhibitor to T3 and T4. Those are your thyroid hormones. So yes, leptin resistance completely turns off your thyroid gland! That does not allow you to burn fat in your muscles because it downregulates your basal metabolic rate. Now you know what controls your metabolism too! That process is called peripheral (muscle) leptin resistance. That is why some fat people can not burn fat with exercise. That is why your thyroid test is close to worthless clinically in leptin resistance. I bet many of you just had an epiphany!

The brain has to get information on the energy status of 20 trillion cells in your body at all times. Due to constraints of space (your skull size), it does not monitor every single cell in the body with a nerve cell connection to complete that task. It uses the endocrine system to do that. That is the system that hormones come from. Leptin is made from your white fat cells in your body. But you first get leptin from your mother when she first breast feeds you. So if you were not breastfed you may have started life off on the wrong foot from an energy metabolism standpoint. In fact, the latest research is showing that not getting leptin from your mother’s colostrum has huge implications right away for your DNA. It affects a chemical process that alters your DNA called methylation. That information is transmitted directly to your DNA and causes a change that leads to epigenetic signals. This is one way we know obesity can be transmitted across generations. There are others.

Leptin enters the brain through some complex signaling that occurs in the hypothalamus. Once it enters the brain it begins to set off a group of neurons that will modulate your energy status for the remainder of your life. This part of your brain is about the size of a pea and it sits right on your nerves that go to your eyes. Imagine a hole drilled between your eyes straight back about 5 inches. That is where all the action happens. The hypothalamus links the brain to all your endocrine system in the body. The endocrine system includes every hormone you have heard of. The hypothalamus also modulates many of the most important centers in the brain. Without energy, no animal could live or carry out any complex tasks. Think about your car for a minute. How far could you go if you never knew how much gas you had? The only way to go anywhere and feel safe is if you just filled up and went. But then again you’d never know when it was time to fill up again either would you? That is precisely what happens to a human when they are leptin resistant. The brain can’t tell what the energy status is in the body. The energy status is your fat cells. Leptin is that connection from fat to the brain. It controls everything to do with energy and information. Without energy or information, everything fails.

Some of the organ systems in the body that rely on energy the most are also tied to leptin status. Once such tissue is bone. Bone is incredibly active as it constantly remodels to stresses it is placed under. To allow a system that wide range of change it requires massive energy sources. That is why leptin is important in bone physiology. Leptin resistance always pre-dates the development of osteoporosis. Leptin also controls the ability of women to get pregnant. That is called fecundity. If a woman is leptin resistant, she will have a lot of difficulties getting pregnant. We see this in PCOS (polycystic ovarian syndrome), in anorexia, or overtraining. Having a baby requires a lot of energy for growth. Leptin is the key for that process to occur smoothly.

Leptin also controls and modulates the immune system in the brain too. It is chemically very similar to an inflammatory chemical called IL-6 (interleukin 6) and in people, with high leptin levels (fat people) we see high levels of white blood cells. It also modulates all the inflammatory cytokines associated with visceral fat. Generally, when someone is leptin resistant they also have low vitamin D levels. I also use this as a proxy to assess leptin status in working up patients. Visceral fat is the fat below your “six-pack” muscle in your abdominal cavity. This is one of the worse places to get fat because it is highly inflammatory. That is also the fat seen in type two diabetics that fills their liver cells. That is called metabolic syndrome or nonalcoholic fatty liver disease. Elevated leptin is also the first sign seen before high blood pressure shows up and causes a cascade of further physiologic problems. The reason for this is that high levels of leptin will destroy another protein secreted in the beta cells of your pancreas called amylin. The beta cells in the pancreas make insulin. So you now know why high levels of leptin (fat) cause type 2 diabetes. The high leptin fries the amylin in the beta cells and causes them to stop making insulin eventually. If it takes a long time it can cause type two diabetes.

If that process happens fast, for example, because of an autoimmune response surrounding a pregnancy or a leaky gut then you can get autoimmune diabetes often called type 1.5 diabetes. The only difference between type 2 and type 1.5 is the time is shorter and the immune response much greater. Again, all mediated by leptin resistance. The chronic leptin elevation leads to eventual leptin resistance and usually occurs 5-7 years before someone becomes insulin resistant! (Type 2 DM) Today’s medicine focuses in on insulin to treat diabetes. In my view, this is completely off target. It makes no sense to treat insulin resistance after it has occurred. It makes more sense to target leptin resistance because it occurs 5-7 years before insulin resistance occurs! It is now clear that obesity is a disease of inflammation. But we know obesity has several causes. Obesity is not a disease of excess calories. Why? Because the body has several built-in ways of dealing with calorie excess without you ever getting fat if leptin is working properly in your liver and your muscles. I promise I will get to that story too soon in a future blog. Obesity is a disease of inflammation and hormonal disruption of hormone signaling. That is why you want your physician to remain vigilant and concerned with measuring your ultra sensitive or cardiac CRP with regularity. Now you know why I do this test on all my spine patients. Leptin problems tell me degenerative disc disease and osteoporosis are going to occur in this patient unless I solve their leptin problems eventually. In my opinion, it is a test that needs to be monitored more than any other in medicine until a better one appears. It can tell us a ton about your current cellular terrain. Remember levee one in The QUILT.  Whatever happens to your cells determines what will happen to you eventually. If your inflammation is elevated bad things are in your future as you will see as the quilt expands.
Here is the key point to take home: Leptin resistance always precedes the development of insulin resistance. (minus traumatic pancreatic loss) Once both occurring long enough it leads to adrenal resistance. And adrenal resistance means you have a problem with CORTISOL. Don’t forget this point. It’s that important. When insulin and cortisol are raised simultaneously and chronically this is how cancer and chronic diseases humans occur by effecting the p53 gene (oncogenesis levee). They all start with leptin problems, not insulin issues.

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  1. patricia knigge June 3, 2011 at 11:02 pm - Reply

    Thanks for explaining. It makes good sense.

  2. Flip June 4, 2011 at 6:48 am - Reply

    Excellent article! This explains so much and makes sense.

    As a result of overtraining and under-eating I have had hypothalamic amenorrhea for 10 years I have been diagnosed with osteoporosis. (I am only 41) Is the osteoporosis reservable at all? I feel as if my hypothalamus has "shut down/shrunk" in an evolutionary sort of way because it hasn't been used for so long.

    Thanks for devoting your time and knowledge to helping others get healthy!

  3. carol n June 4, 2011 at 2:17 pm - Reply

    "Obesity is a disease of inflammation and hormonal disruption of hormone signaling. That is why you want your physician to remain vigilant and concerned with measuring your ultra sensitive or cardiac CRP with regularity. Now you know why I do this test in all my spine patients. Leptin problems tell me degenerative disc disease and osteoporosis are going to occur in this patient unless I solve their leptin problems eventually. In my opinion it is a test that needs to be monitored more than any other in medicine. It can tell us a ton about your current cellular terrain. "

    Hi Jack… I am so glad you are starting to write your Quilt manifesto. I realize it will many layers and 3-dimensional… but I am wondering if you can help me out with the above statement. The second sentence is the first time you mention the ultrasensitive or cardiac c-reactive protein test… so it is not clear to me why you do this for your spine patients or how it relates to leptin resistance.

    Could you please explain how it relates to leptin resistance, why it needs to be monitored regularly and what it tells us about our cellular terrain?

    Also, if you say that we can tell if we have leptin resistance by looking in the mirror… how do we begin to make our muscles and hypothalamus senstive to it again? Thank you so much!

  4. admin June 4, 2011 at 5:48 pm - Reply

    Cardiac CRP is the same as an ultra sensitive CRP. The reason I do it in all spine patients is because all spine disease is mediated by inflammation as well. The causes of those issue will be laid out much later in my blog. This blog focus is not about spine disease per se but you can see bone metabolism is greatly effected by poor energy utilization. So anyone who has leptin resistance is at serious risk of developing osteopenia or osteoporosis. I can tell you in 2005 when I realized this it changed the way I work up all spine disease. Cardiac CRP is the best biomarker we have that is both sensitive and specific for the cellular markers of inflammation we worry about most namely, TNF alpha, IL6 and NF kappa beta. Fat cells specifically raise TNF alpha and IL 6 in great quantities when fat is abundant or in the visceral compartment. (leptin resistance) It winds up in the visceral compartment because of hepatic (liver) leptin resistance. Its our signal that your cells are on FIRE!

  5. admin June 4, 2011 at 5:51 pm - Reply

    Looking in the mirror tells you if your fat or anorexic! Your vision does not lie to you unless your blind. It's your best clue you might have a problem. If you're not sure…..then we go to the next best test, the reverse T3. That test has never failed me yet. Most people in plateau's usually are there because of a spike in reverse T3. T3 immediately shuts off your thyroids ability to effect metabolism. Stress mediated by cortisol is the usual suspect. I will be hitting cortisol big time because it is a huge factor in most of the patients I see clinically and there I believe it to be true in the general population.

    In my patients who are going to be going to surgery eventually we see their reverse T3 jump up huge because of the cortisol release. That shuts down their metabolism and they don't recover as well and it effects their prognosis because they can not heal their wounds as well. Chronic Pain is another big cortisol issue. Hope this explanation helps.

  6. carol n June 5, 2011 at 5:48 pm - Reply

    Thanks so much… yes your explanation helps. I did a little googling after I posted on CRP and leptin resistance, so I understand it a little more… it gets very complicated, very quickly so I know it's hard to put it in lay terms…. thanks for putting it out there tho.

    And re the cortisol… I've been reading about that as well… it's interesting that I have recently discovered that due to a very violent childhood, I have PTSD… and I (and my brother) became overweight at ~7 yo… (w/genetic obesity on both father and mother sides)…. I've been working on mindfulness techniques to help deal with the PTSD… maybe this will help w/WL… have been on atkins for about a month… strict induction. and have lost only 3 lbs, altho feel better and inflammation is down. I will keep on keepin on, practice mindfulness and keep reading! Thanks again.

    • admin June 6, 2011 at 11:33 pm - Reply

      I am a huge believer in mindfulness and you can find many of my posts at paleohacks.com about it. I also would tell you to reconsider Atkins…..get Robb Wolf's book and go pedal to the metal. that is the Rx i hand out to all my patients who want the weight to come off. then I micromanage it.

  7. Linda June 6, 2011 at 2:01 pm - Reply

    Thanks for the great work. I just want to make sure I ask my doctor for the correct thyroid test. I've had a test called "T3 Free Tracer Dialysis" done about a year ago. Is that the test you use?

  8. stereotactic surgery June 7, 2011 at 10:56 am - Reply

    Thanks for providing this article. I very much enjoyed it. Keep up the excellent work, dude!

  9. Lisa June 7, 2011 at 12:40 pm - Reply

    What Reverse T3 score is a red flag? I recently had one done but doc said it was okay. I want to look it up when I get home.

    Thanks for the awesome articles! Very educational.

  10. Alma Brunderman June 7, 2011 at 4:45 pm - Reply

    What would it take to for me to create a blog like yours? I found your blog on Yahoo

    • admin June 7, 2011 at 6:53 pm - Reply

      Just sign up for word press and have go at it. I am new to this as well. I write as I think. This is not meant to be a novel…….just a place to share ideas worth sharing

  11. SallyS June 10, 2011 at 5:06 am - Reply

    Having just read this, the thought that springs to my mind is could Leptin resistance be linked to pre-eclampsia? I am just a Mum not a medical person, just it makes me wonder.

    • admin June 10, 2011 at 7:47 am - Reply

      Yes leptin resistance is strongly linked to pre eclampsia and future development of type two diabetes of the mother and the child. Epigenetics at work here by methylation of chaperone proteins. (another levee in The Quilt)

  12. Lisa June 10, 2011 at 10:55 am - Reply

    That link was great! Well my ratio is 10.7. It's supposed to be at least 20. Now I know why I'm having some problems. But I'm confused about what to do about it.

  13. SallyS June 11, 2011 at 10:30 am - Reply

    Thanks for answering. That's fascinating, because I have had pre-eclampsia with one child and high sugar levels with another. So they are linked.

  14. Art Deco June 25, 2011 at 7:44 pm - Reply

    I see they're saying now, officially and in the mainstream media, that diabetes can be fixed by dieting. They've been saying that for years, though, in the alternative press, that and more too; some have said that cancer can be cured, or at the very least slowed down, by low-carb dieting. A few years ago that would have been held improbable, but so would the diabetes cure. We are indeed what we eat, apparently. How much more has been kept from us, I wonder?

  15. pam August 14, 2011 at 5:49 am - Reply

    "Testing leptin is easy to do but rarely done in medicine today. The easiest way is to look in the mirror. If you're way too fat or way too thin guess what? You are leptin resistant, most likely."

    Thanks for sharing. I've always been light and thin, so this is important to know. What are the differences between leptin-resistance in skinny compared to obese?

    • Jack August 14, 2011 at 9:25 am - Reply

      For the thin I am a big believer in checking reverse T3 and a full thyroid panel with antibodies…….its critical. Samething with O6/O3 ratio.

  16. pam August 15, 2011 at 6:41 am - Reply

    I've been monitoring my thyroid for about 2 years, roughly it has run this course:

    fT3: 3.4 1.9 2.4

    fT4: 1.4 1.2 1.3

    TSH: 2.7 3.8 3.2

    TPO: <10

    Celcius before rising: 36.3 36.6

    So recently there seem to be slight improvements again. Guess it's due to the iodide increased to 12mg, beside other supplemental support. But just as well be mere natural fluctuations. HbA1c has been about 4.8 (+/-0.4) and fasting glucose averaged at 98 mg/dl. C-peptide came back at 1.57 ng/ml and recent fasting Insulin at 8.6%, calculated Insulin resistance (Homa) from these values seems stable at about 20%.

    Since tracking I carry a long list of blood tests I think necessary to do, and with each regular visit I try to get my GP to add one or the other. And save my little money for those I consider essential without a slight chance to get it done for free, like 25(OH)D or a yearly hair mineral analysis (have quite some electrolyte imbalances going on, while supplement heavily but quite successfully against a PAD, ie. Pauling, Dr.. Davis..) and supplements (very expensive for me, have to import most to Europe from overseas). So at moment more urgent things to monitor, like my elevated E2 (50 pg/ml) and how it might have responded to the measures taken against..

    In the view of not getting the rT3 test for free (though I haven't given up to educate my GP on thyroid, etc..) and an – to some extent – obvious leptin-resistance, would the rT3 test really add critical additional information?

    In other words, at which lab value of rT3 would your standard advise against-leptin resistance be substantially different – and how?

    O3:O6 ratio is an other test which would be difficult for me to get. Therefore I monitor my nutrients intake, which for these come back at 10g:20g from diet, and an additional 4.4g EPA/DHA per day during the last 2 years.

    • Jack August 15, 2011 at 10:00 am - Reply

      More data…..height and weight …..body composition? HS CRP level? Vit D level?

  17. pam August 15, 2011 at 7:23 pm - Reply

    You're amazing! Didn't meant to steal your valuable time with too much details about my case.. However, I'm really grateful you do 🙂

    I'm 43 years of age, 5.7 feet and 132 pounds (173cm and 60kg). My last CRP tested has been 0.05 mg/dl. But not the hs-CRP typ, which is one of those many tests on my do to list..

    Vitamin D has been around 60 ng/dl tested twice during the last year, but surprisingly came down to 27 this March, despite having increased the daily dose to almost 10.000 from about 8.000 IU last year. I suspect the simultaneously increased preformed vitamin A (for balancing all fat solubles) as the culprit. So have decreased the A and am about to retest D3 soon.

    If you find the time you could take a closer look at all my results (including supplement intake) at a google spreadsheet:
    (but better delete this link again 'cos some things like dhea or melatonin are actually restricted where I life)


  18. Jack August 15, 2011 at 7:36 pm - Reply

    @Pam…….without going into detail my bet is you have not a leptin issue but a perimenopausal issue tied to cortisol and pregnenolone steal syndrome. With minor hormone testing you can be rebuilt it appears. You just need finishing touches. I don't like the fasting glucose so it tells me your estrogen dominant and may still need to push that thyroid functioning……but those are guesses without labs.

  19. pam August 15, 2011 at 7:55 pm - Reply

    Quite accurate. I got diagnosed with PAD (with a walking distance down to 3-400 meters) right after quiting a job with too much constant stress, which I stupidly endured for 2 years.

    I don't like my glucose either, but since it doesn't really relate to my HbA1c – I suspect the high dose vit C is interfering with the testing..

    "You just need finishing touches."

    Hmm.., considering my wholly occupying shot-gun approach to my difficulties, will have to ponder this some time..

    Meanwhile, if you had only a hundred bucks to spare, to which hormone tests you would give absolute priority?

  20. Jack August 15, 2011 at 8:03 pm - Reply

    @Pam salivary cortisol level is the money shot I bet

  21. pam August 16, 2011 at 3:18 am - Reply

    Slept over it. And it's funny, because I already thought the same about merely having to find the right 'touches':

    Beside the 2 years of constant stress, which might have been the ignition to my hormonal in-balances, and in the context of having been a vegetarian since 10 years of age, a smoker for not that much less – which both probably have been big contributing factors – the main stenosis at my abdominal aorta (~60 – 80) is also at a very auspicious place:

    Right at the height where I had a spinal inflammation about 12 years ago! (thought it was a displaced disc at that time and in a country without good medical care; only Ibuprofen helped to dive through this painful episode which lasted 8 month)

    In the context of my situation of not having found a practitioner who understands hormones yet, do you think the salivary cortisol profile will help me finding the right course of action 'doing it myself'?

    Because already now I know I get really tired in the afternoons, and am much too active after dusk. And though the OTC supplements available to me did help already much, I'm still searching for the 'final touches'.

  22. Jack kruse August 16, 2011 at 7:10 am - Reply

    I think it is possible Pam

  23. pam August 17, 2011 at 5:50 am - Reply

    Thanks for your optimism. I'll keep searching..

  24. pam August 30, 2011 at 8:22 am - Reply

    "So at moment more urgent things to monitor, like my elevated E2 (50 pg/ml) and how it might have responded to the measures taken against.."

    Quick question. Could get a new lab of my E2 again and it showed <10 pg/ml, with a lab reference range of 11 – 44. Therefore my question, what kind of problems could a E2 too low pose for men?

  25. pam August 30, 2011 at 8:51 am - Reply
  26. Jack August 30, 2011 at 6:01 pm - Reply

    E2 elevation for men is not good. Your graph shows that but the cause is usually aromatization from fat or from dramatic swings in SHBG. The other issue is exogenous steroid use or phytoestrogen driving it. I have seen some vegan men with unreal E2's because of excessive soy use.

  27. pam August 30, 2011 at 6:26 pm - Reply

    Thanks for an answer, though you must have misunderstood. because with the latest lab my E2 dropped down to <10 pg/ml. So in this case I should excessive soy would help to get it up in range again? :-O

    • Jack August 30, 2011 at 8:43 pm - Reply

      @Pam…..soy is never suitable for any human to eat in my view. If you want to raise E2 you got to find out why its low. In a womans case it could be early perimenopause or menopause genesis.

  28. pam August 31, 2011 at 8:25 am - Reply

    Is it possible to tell which supplements I take (see link in post 25 above) could possibly be the strongest aromatase inhibitors?

  29. jpatti September 9, 2011 at 11:20 am - Reply

    Why are you not treating rT3 with T3? Protocol at http://www.thyroid-rt3.com/

    Also, before that, why is diet the protocol for adrenal issues? Why are you not treating with hydrocortisone (HC) given in a normal circadian rhythm as per http://adrenalsweb.org/steroids.php or something similar.

    I don't understand how when your cortisol is crashed, and your rT3 is elevated, and you're basically completely sleep disordered and bedridden, 50 g protein in the morning is going to fix anything? Also, eat it within 30 minutes of waking? WHICH waking? The one at midnight, or 2 AM, or 4 AM or 6 AM or 8 AM?

    I do "get" that leptin is the FIRST problem, and I'd prefer shots of leptin to opvercome LR instead of insulin to overcome IR. As far as I know, it's not available though.

    But… I do not get how the heck you could possibly fix ANYTHING with adrenals crashed and nearly no cortisol and running on adrenaline instead… and rT3 stuck in all your T3 cell receptors… without meds to normalize.

    HC fixes the circadian rhythm first so you sleep normal and can get out of bed (if you take enough to suppress your HPA axis). Then T3 suppresses thyroid so you don't make T4 anymore so your body can't keep making gobs of rT3. Then you can begin to heal.

    I just don't see how a big pile of eggs could possibly fix this. Sure low-carb is the thing to do… and sure real food beats the heck out of crap, but geez, I ate mostly pastured meat, pastured eggs, pastured raw dairy, organic nonstarchy veggies and low-sugar fruits for YEARS and was still bedridden until I got on HC and T3 meds.

    Also, you don't seem to address… well, the fact that the vast majority of the medical establishment is not convinced by basic biochemistry. They want drug trials.

    One pretty much has to do the salivary cortisol on one's own, do the rT3 on one's own, interpret the results on one's own, figure out the meds on one's own, and source them on one's own. Unless one lives near Holtorf or you or another doctor with half a clue (I've never yet met an endo with one), one must pretty much determine to self-treat if one wishes to recover.

    Well, I haven't read the entire quilt yet, maybe there's answers in there. But for now, I just don't get it.

  30. pam September 15, 2011 at 10:54 am - Reply

    quote pam: "..could possibly be the strongest aromatase inhibitors?"

    quote Jack: "If you want to raise E2 you got to find out why its low."

    Though I still don't know exactly what's going on, with a few more lab results now I definitely know something is indeed happening undercover and unrelated to supplementation.

    Except homocysteine, thyroid and liver functions (for which I'm already very glad), all other values got really worse. Haven't even seen such a high Lp(a) yet, beside worst lipids since starting this odyssey.

    Most worrying is glucose tolerance, while having carbs gradually further decreased. During the last 3 weeks fasting glucose averaged 123 mg/dl!!!, postprandial at 139. HBA1c came back 5% (relatively high for me) and Fructosamine at 230µmol/l.

    A CRP of 0.23 mg/dl (again, relatively high for my usual values) suggest to me some hidden infection is breeding, which may explain my suddenly extremely low E2 too.

    quote Jack: "@Pam…….without going into detail my bet is you have not a leptin issue but a perimenopausal issue tied to cortisol and pregnenolone steal syndrome."

    quote jpatti: "..has to do the salivary cortisol on one's own, do the rT3 on one's own, interpret the results on one's own, figure out the meds on one's own, and source them on one's own. ..one must pretty much determine to self-treat if one wishes to recover."

    Thanks for your contribution, Patty: A concise summary of what I've got to do (once my bank account allows 8-(). Since a leptin reset probably wont do it in my case – and each additional doc I visit seems to be more useless than the one before..

  31. […] were able to jump straight into topics such as Jack Kruse’s Leptin theories, Nora Gedgaudas’s Australian Primal Body Primal mind conference, the AHS and how we […]

  32. Mimi November 18, 2011 at 11:43 am - Reply


    I'll be interested to see Dr Kruse's reply to you. My guess it's going to be that there are different causes of adrenal failure like yours (sounds like you have Addison's Disease??–actual adrenal failure, rather than simply moderately insufficient level?).

    Dietary & sleep changes can make a difference if doing those wrong started the problem. That doesn't sound like your situation–so something else may have caused the catastrophic hormone failure you have experienced. In such extreme cases, some people need direct cortisol supplementation just to stay alive.

    He mentions how this post excludes traumatic injury to the pancreas as a cause of diabetes. This illustrates my point exactly. If people mess up their pancreas by how they eat, they can optimize it by eating right. If, however, they lose pancreatic function due to the trauma of say, a car accident or major surgery, then diet will not fix it, because diet did not cause it.

    You seem to be the adrenal equivalent of this, tho I could be wrong, and I don't know what could have caused your adrenal failure…perhaps genetics, perhaps something not evident here.

    Cures/remediation are based on addressing the CAUSE. If your cause is different than the focus here (living contrary to the Leptin Reset protocol & thereby messing up both leptin & insulin), then you may need a different treatment…tho the leptin reset protocol may support your healing along with that other treatment.

    My heart goes out to you, and I hope you find the answers you need.

    Dr. Kruse?

  33. Mimi November 18, 2011 at 11:56 am - Reply


    To answer your question more directly on how these things work for those who need it, Dr Kruse explains:

    "…I realized that we might be able to do the same thing for obesity if we could retrain the brain how to account for food without using the newly discovered leptin receptor. Back in the late 1990's I did not have the knowledge of how to use alternative central and peripheral pathways in the nervous system to do this, but in the last 10 years I think I came up with a way to do this using circadian rhythms, light, timing, and the stretch receptors innervated by the vagus nerve in the gut that controls our entire gut plexus. The vagus nerve is the afferent nerve of the brain gut axis as well."

    This is the foundational thought of the leptin reset & is on his page:


    I hope it is okay that I am answering (just for interim thought, certainly not presuming to have this all right!), as I see this thread has been quiet awhile & Dr Kruse mentioned that he is on vacation this week.

  34. MimiDiet December 13, 2011 at 9:34 pm - Reply

    Jpatti–he just did a whole blog post on this very topic!


  35. becky December 26, 2011 at 7:09 pm - Reply

    Dear Dr.Jack,

    i got blood work done. looks like they tested 29 things. i don't understand it and they won't explain except to say that everything is normal except thyroid which is Thyroxine, Free result: 10.1 reference 9.1-23.8 pmol/L and TSH 16 Flag H reference 0.30-4.2 mU/L

    Hypothyroid: > 15 mU/L

    i got the blood work done cause i find myself staggering sometimes and forgetting words. would these thyroid results explain my symptoms?

    she took my blood pressure and she wasn't going to say anything but is asked, is it high and she said 'a little'.

    56 female, 10 – 20 pounds overweight on my 5 foot frame. i think i have candida issues – constantly craving sweets.

    will be stating the leptin reset tomorrow.

    i really really appreciate your help.

  36. mary January 17, 2012 at 6:53 am - Reply

    If there existed a website explaining leptins, insulin, and thyroid balance for the NONOVERWIEGHT, that does not continuously skew the information toward losing weight, it would get my attention. There are millions of people who are TOO THIN, and cannot find information on the above body chemistry issues that isn't toward losing weight. We can't use the info posted for overweight people.

    • Jack January 17, 2012 at 8:50 am - Reply

      @Mary, by your question alone its clear you really do not understand these concepts. Leptin is best understood by inflammation not by obesity. Obesity is but one of the results of disordered leptin biochemistry. There are two tails of leptin resistance……one is fat and the other deathly thin………both are profoundly leptin resistant.

  37. Pieces of the puzzle January 29, 2012 at 1:32 pm - Reply

    Hi Dr. Kruse

    Okay, so not receiving leptin from your mother's colostrum affects methylation right? Could this be cause of Methyl Cycle Mutations such as MTHFR?

    If you are LResistant and bfeeding how does this translate for your babe?

    I started the reset 2 weeks ago and have noticed too much protein in my diet makes my daughters (2) urine wreak of ammonia. I'm talking eye tearing levels. I believe this is due to some inborn error of metabolism or methyl cycle mutation. Is there any reason the reset should be followed in situations such as this?

    I love your site and have been reading for a couple of days but need to spend a lot more to really comprehend. Thank you so much for all you are and do, a true life's purpose and beautiful example for all! Thank you, thank you.

    • Jack January 29, 2012 at 2:10 pm - Reply

      @Pieces…..you will get cat pee smell of the urine…..but I am not sure what yoru asking. Your kids are on the reset or just the paleo diet or are they eating on the post Leptin Rx? It makes a huge difference. Also if the kids have a kidney issue that is another confounder…….as for methylation it does happen. but the major effect is this……if mom Is LR the child is likely going to as well because the leptin receptor also controls the placental function in all eutherian mammals. This in turn means the child will be born with a leaky gut. What can close the leaky gut is colostrum from Mom's milk. One big problem……LR moms cant make milk well. That is a huge issue. That is why LR moms should not have babies until they fix it……or plan on buying banked human milk. The second larger problem is that the child gets leptin from the mothers milk. This source acts like the USB drive for the leptin receptor in the hypothalamus in the child. If it never gets the proper signal the child cant account for electrons from food as it was designed……so it defaults to its own hormonal status that is driven by its diet the first 6 yrs. During those six yrs all the neurons in the hypothalamus are "listening to the signals from the diet and they begin to fire in certain patterns. We call this Hebbian learning in neuroscience. So what the kid eats a ton of determine how it responds to food. The hormonal response of the food then DRIVES THE METHYLATION PATTERNS on their DNA. Originally they were first set by maternal grandmom, then mom in utero…….and now by child forst 6 yrs. I laid all this out in the transgenerational epigenetic blog. Read it. It will help you get it. This altered methylation then selects for the type of microbiota that will grow in the gut. It sets the stage for future neolithic diseases.

  38. Pieces of the puzzle January 29, 2012 at 8:08 pm - Reply

    Great read, i had not gotten that far yet, thank you.

    Sorry for not clarifying, i am on the GAPS diet (just over 1 year) and doing the reset (week 2). My daughter (2) is on the gaps diet (just over a year) and is still breastfeeding. It is her urine that worries me so. This is not cat pee but straight up ammonia. Is this likely kidney failure? She eats a ton of protein as her gut won't tolerate much else. Which correlates perfectly to "this in turn means the child will be born with a leaky gut". But i also notice the ammonia gets worse when i eat a lot of protein. I really need to figure this out for her, it's really bad.

    We have had trouble breastfeeding from day one, but my milk seemed to come in okay it was only after a couple of months that my supply took a nose dive. Which i attributed to poor latch issues. But come to think of it she didn't get the appropriate colostrum! We had the latch issues and i was terribly torn up so they sent me home with a breast pump and some formula for her. I pumped until my milk came in and then resumed bfeeding. Sounds like i will need to do the reset with her at some point too.

    Will do some research on the Hebbian learning. Thanks. I'm trying so hard to put all of these pieces together. So much more reading to do!!

  39. THE HOLY TRINITY: CT-4 - Jack Kruse February 28, 2012 at 9:41 pm - Reply

    […] learned how leptin controls hormones in some of my first blogs.  If leptin is not working, sleep or metabolism are by definition, become suboptimal because […]

  40. COLD THERMOGENESIS 5 - Jack Kruse March 3, 2012 at 10:10 pm - Reply

    […] time as our cells are recycled in sleep with autophagy.  This is where the cytokine storms and leptin resistance comes from that shorten our telomeres and age us faster.  These cytokines are the fuels that speed […]

  41. LBK March 13, 2012 at 4:01 pm - Reply

    I am considering getting tested as your recommendation for the thin: reverse T3, full thyroid panel with antibodies, and O6/O3 ratios. If LR occurs in the overweight and the extremely thin, how thin is too thin? I am female, 48yrs. old, 5′ 8.5″ and now weigh abt 117 to 118 lbs. I don’t know my exact body composition, but I would say under 15% body fat, and muscular. I do both resistance and cardio workouts as well as yoga. I have had about one menstrual cycle in the last 6 mos. and maybe one in the 6 mos. prior to that. Peri-menopause started abt late 30″s. Oct. – Dec. 2011, I did a 12 week group finess program (included cal. counting, low fat, higher protein and carbs) to lose a couple lbs. but lost abt 8-10. From 126-128 to 118. I have held at 116-118 since Dec. 2011. For several years I have been taking bio identical hormone cream, dosage evaluated yearly, currently: (E2 2.25MG, P 35MG, and T 0.75MG/GM EE) 1/4 tsp. daily and Liothyronine Sod Tab 5MC, 2x daily. For the past month I have been eating a mostly paleo type diet (higher protein and sat. fat, lower carb) and don’t count calories. Cut out gluten grains several months ago. Prior to this, since childhood, I ate lots of carbs/sugar. What I have problems with (always have, but seems worse with age) is foggy brain, low energy, and concentration problems (unless it’s something I’m interested in, then I’m extremely focused to the point of ignoring everything else-overfocused ADHD). Mostly “off” days with occasional “on” days. My main social interactions are at the gym. Decreased social interest with age. Don’t do much outside of family. (Stay at home mom). Could any of this be tied to LR?

    • Jack March 13, 2012 at 5:33 pm - Reply

      @LBK Testing always helps…….

  42. LBK March 15, 2012 at 3:08 pm - Reply

    Thanks so much for sharing your knowledge and advice, Jack, and being genuinely concerned for others. I am starting the leptin reset today. Decided not to wait for testing. I am due for a check-up soon and will have tests done then. (Figured I must be LR given being borderline hypo-thyroid and my intense cravings for carbs. The cravings are not as bad though since going paleo about a month ago.) Just need to go another step and eliminate potatoes, rice, and snacks. So, no cardio or weights till LS, even if not overweight, correct? Are muscles sugar burners and not fat burners even if low % body fat, due to previous high carb intake? What about yoga and pilates, and if O.K., is timing important for these less intense exercises? (work-out addict here).

  43. Brian April 16, 2012 at 10:50 am - Reply

    Hi Dr. Kruse,

    Just discovered your website. I’m devouring this stuff. I’m 38, lost 83.5 lbs in the last 8.5 months by going low carb/paleo, but 75+ of that was in the first 5 months. My O6 intake could be better but otherwise I think I’m good.

    Thing is, I’m stalled, and have been for nearly four months. I figure I need to lose another 40 lbs. I still have a lot of goo on my belly and I can see the weight in my face, though the progress I’ve made is astounding to me and others. But I can tell what I’m doing isn’t quite right. I’ve been doing a lot of IF but I get ravenously hungry and often times, huge Paleo meals aren’t fulfilling. I’m clearly not burning fat anymore. I never eat breakfast. Tried that today immediately upon waking and wow, I’m feeling great! Better than I have in a while.

    I’m starting the leptin reset protocol today. I’m not sure if I should be HIITing yet. Or walking. I feel like I’m at a halfway point, having made so many positive changes and seen dramatic results (NAFD, gone; insulin sensitivity is largely back, dropped so much weight, etc.). I plan to read all of your blog. Can you point me in the right direction here? There’s a lot. I’ll get to it eventually.

    Thanks for all the help.


    • Jack April 16, 2012 at 11:11 am - Reply

      @Brian you need to really read my blog post on 2/11/2012 on CT.

  44. Brian April 16, 2012 at 1:44 pm - Reply

    Heading there right now. Thanks!

  45. Galen April 22, 2012 at 2:18 pm - Reply

    I’m not overweight (5’8″, 150#, small to medium frame) female, but i’m seeing a steady increase in weight gain over the years (ideally would like to be about 138 or so). Am relatively active, but travel and sit for living. Thing is, I really don’t even get the amount of calories I probably should each day (assuming 1800-2000 cal/d) to stay even with metabolism. Probably get in the range of 1200-1400 on a good day. I don’t eat too much in the way of carbs, yet i’m still trending upward. Chems are ok (226 chol in Feb w/78 HDL). No bone disease on last bone density, but cervical and lumbar osteophytes have recently reared (motorcycle accident 30 years ago, chickens roosting now). In short, I’m pretty average aging female, so how does this leptin thing apply to someone like me who doesn’t need to loose much weight, just optimize gracefully? Thanks so much for what you are doing.

    • Jack April 22, 2012 at 4:28 pm - Reply

      @Galen if you want to stay fit and healthy and away from doctors it applies to you. Just read the blog and join the forum…..before too long you will wonder what took you so long.

  46. Galen April 22, 2012 at 2:21 pm - Reply

    o, should add, 58 yrs old.

  47. […] total energy balance in the body.  This maybe a good time and go back and re read Leptin part 1-3 blog posts.  (each link is embedded with a different leptin […]

  48. Tim February 18, 2016 at 11:54 pm - Reply

    Hello my father has a tumor on the side of his tongue. He is on a zero carb, bone broth with the herbs you suggest(tumeric, ginger, onion,garlic, rosemary), no meat other than broth, crucifers cooked with broth, tablespoon raw liver daily, lots of coc. oil, vit b supps, D3, meditating daily, serious about barefeet on earth, circadian rhythms, dark room sleeping, minimizing EMF’s. He wakes up at night after 2-3 hours sleep, paces for hours before sleeping again for 1-3 more hours. What would be the lab test to have done to get some solid feedback? Or is there an obvious route(s) to try first. Your information thus far has been a very helpful addition to working with this sir.

    • Jack Kruse February 19, 2016 at 7:29 am - Reply

      Tim I don’t know your Dad so I could not suggest anything specific. Poor sleep is a sign of broken melatonin signaling at night. I’d suggest you read the Time 9 blog to see the link to disease. As for testing an Adrenal stress index with salivary melatonin level might be very instructive in a situation such as his. These days he can get his own labs without a Rx if he goes to a place like “anylabstest.com”. This can be discussed with his doctors too.

  49. […] years, to first become leptin and then insulin resistant. According to some sources, you are likely leptin resistant 5 to 7 years prior to becoming insulin […]

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